Personal lubricants comprising lambda-carrageenan

The present invention relates to a method for making a personal lubricant composition useful for reducing or inhibiting the transmission of human papillomavirus between partners during sexual activity.

2. Background of the Invention

According to the World Health Organization (WHO), human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the world, with more than 14 million new infections each year. In the United States alone, more than 42% of people between the ages of 18 and 59 are infected with HPV, and one in nine men is infected with oral HPV. Additionally, HPV is essentially the underlying cause of all cervical cancers, the second most common cancer in women worldwide by age-standardized incidence, responsible for approximately 500,000 deaths annually. More than 85% of cervical cancer deaths are in developing countries, accounting for 13% of all cancers in women. The WHO also estimates that HPV causes 90% of anal cancers. In another study on HPV and pharyngeal cancer, AECOM found that the presence of HPV types in the mouth increases the odds of developing head and neck cancer by 22 times. HPV is also the underlying cause of all genital warts.

HPV spreads through skin-to-skin contact and is most commonly transmitted to the genitals, anus, and mouth during sexual intercourse. As a result, condoms are only marginally effective at preventing HPV transmission. Although there are several treatment options for HPV, there are in fact over 150 strains of HPV, of which approximately 30 have been shown to cause cancer and genital warts. Vaccines have been developed and may be useful, but the best HPV vaccines currently available in the United States only show antiviral activity against 9 of the over 150 strains of HPV, making them effective in only a minority of people. In 2015, the CDC reported that HPV vaccines have only a 40% uptake rate among adolescents and are generally ineffective in people over the age of 26, as well as African-American women of any age. Additionally, the CDC reports that the vaccine is also ineffective if there has been previous exposure to HPV. Additionally, HPV vaccines are generally expensive, require multiple treatments or injections, and are rarely available to people in developing countries. As a result, many people are not vaccinated and rely on condoms as their only defense against HPV.

in vitro (see Buck, CB, et al., (2006) PLoS Pathogens 2(7):671-680) and in vivo in mice (see Roberts, JN, et al., (2007) Nature Medicine 13 (7):857-861, and Maguire, R. There has been some promising research into the use of carrageenan preparations, particularly those containing the lambda form of carrageenan, to reduce or inhibit the transmission of various viruses in humans (see, e.g., A., et al., (1998) Sexually Transmitted Diseases 25 (9):494-500). Several other patents and patent publications also discuss the use of carrageenan in pharmaceuticals as an antimicrobial or antiviral compound (see U.S. Pat. Nos. 5,208,031 and 8,367,098, and U.S. Patent Publication Nos. 2005/0171053, 2005/0239742, 2005/0261240, 2006/0127340, 2008/0227749, 2009/0088405, and 2011/0229446, the disclosures of which are incorporated by reference in their entireties).

More recently, in vivo studies in humans have demonstrated that lambda-carrageenan formulations can be used to inhibit the transmission of HPV during sexual intercourse (Magnan, S., et al., (2019) Clin. Microbiol. Infect. 25(2):210-216, the disclosure of which is incorporated by reference in its entirety). However, few commercial personal lubricants contain carrageenan because carrageenan is very difficult to process into a form suitable for use during sexual activity. Carrageenan is a large, flexible polysaccharide, most of which is obtained as a complex mixture of at least two, and usually three, different forms: kappa-carrageenan, iota-carrageenan, and lambda-carrageenan, which differ in the degree of sulfation. The kappa and iota forms of carrageenan have the lowest number of sulfate ester groups per molecule, dominate most carrageenan mixtures, and are typically used as gelling or thickening agents in the food or cosmetic industry. Lambda-carrageenan, on the other hand, has the highest number of sulfate ester groups per polysaccharide and is unable to form gels at all. For lambda-carrageenan, increasing sulfate ester levels generally decrease the dissolution temperature in water, which is closely associated with decreased gel strength or inhibition of gel formation. When present, every combination of kappa, iota, and lambda forms of carrageenan has an exponential effect on the viscosity of the composition as a function of the total concentration of carrageenan in the composition. This can result in loss of rheological, tactile, and performance benefits when the composition is used as a sexual lubricant. In particular, carrageenan-based formulations tend to dry out quickly after application, resulting in a sticky, non-lubricating residue that defeats the purpose of using a personal lubricant in the first place. Furthermore, the viscosity of a particular carrageenan-containing composition is very sensitive to the exact proportions of kappa, iota, and lambda forms in the composition. Thus, a composition containing 50% lambda-carrageenan and 50% kappa-carrageenan will have a different viscosity than a composition containing 70% lambda-carrageenan and 30% kappa-carrageenan, even if the total concentration of carrageenan in both compositions is the same. This effect is exacerbated in compositions containing all three forms of carrageenan. As a result, the viscosity of carrageenan-containing compositions is generally unpredictable from composition to composition when the percentages of kappa, iota, and lambda types are different, even when the total concentration of carrageenan is the same.

In addition, the processing steps used to produce the carrageenan-containing composition itself can affect its viscosity and performance as a sexual lubricant. For example, the temperature at which the ingredients are mixed can dramatically affect the viscosity of the carrageenan-containing product, especially as a function of the ratio of each form of carrageenan in the mixture. When an unprocessed carrageenan mixture is placed in an aqueous solvent and heated, the individual polysaccharides in the mixture begin to hydrate and begin to interact intermolecularly with the other polysaccharides, increasing the viscosity of the composition. Further increases in temperature disrupt the intermolecular interactions, homogenizing the carrageenan and incorporating it into the aqueous phase, lowering the overall viscosity to near the starting level. However, the proportion of each type of carrageenan contained within the composition can affect what happens upon cooling. If the predominant type is kappa- or iota-carrageenan, the cooled composition will form a gel, but if the predominant type is lambda-carrageenan, the cooled composition will not form a gel. Nevertheless, the relative proportions of kappa-carrageenan and iota-carrageenan in the composition will affect the viscosity of the lambda-carrageenan-containing composition that does not gel.

On the other hand, excessive heating of carrageenan-containing compositions has the effect of breaking intramolecular bonds between adjacent sugar units, effectively causing significant changes in carrageenan molecules and reducing their average molecular weight.This can further reduce the viscosity of the resulting composition, but with the tradeoff that the composition dries more quickly when applied.Similarly, mixing carrageenan-containing mixtures at high speed or under high shear conditions for long periods of time can disrupt the intra- and intermolecular relationships of carrageenan molecules in the composition.

Thus, there remains a need for a formulation that contains lambda-carrageenan and also functions well as a sexual lubricant, allowing both men and women to protect themselves from HPV infection in a comfortable and discreet manner. Lubricant formulations must balance effectiveness against HPV while maintaining the improved viscosity, tactility, and performance that can be obtained by using personal lubricants during sexual activity. There also remains a need for a product that can be used in combination with condoms or other sexual accessories to reduce the risk of contracting HPV, HIV, and herpes during sexual activity, especially when two or more men are involved.

The present invention provides a method for producing a low viscosity antiviral lubricating composition comprising lambda-carrageenan and useful for reducing, inhibiting or ameliorating the transmission, persistence or symptoms caused by viruses, including but not limited to sexually transmitted viruses and other pathogenic viruses from taxonomic families, which may be any one of or selected from the group consisting of Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, Coronaviridae, Retroviridae, Herpesviridae, Papillomaviridae, Picornaviridae, Reoviridae and Adenoviridae, and combinations thereof. The antiviral lubricating compositions made according to the disclosed processes can be applied to epithelial or skin tissues where viruses may be present or spread, including tissues in or on the cervix, vulva, vagina, clitoris, penis, anus, mouth, nose, nasal cavity, or throat.

In various embodiments, the antiviral lubricant composition made by the method of the present invention can be used in conjunction with sexual activity. As used herein, the term "sexual activity" includes intimate or sexual contact with the skin or epithelial tissue in or on the cervix, vulva, vagina, clitoris, penis, anus, mouth, or throat of one, two, or more sexual partners. In some embodiments, application of the antiviral lubricant composition of the present invention is effective in reducing the transmission of sexually transmitted viruses in humans, non-limiting examples of which include human papillomavirus (HPV), human immunodeficiency virus (HIV), and herpes simplex virus (HSV), compared to a placebo composition that does not contain lambda-carrageenan. In further embodiments, the antiviral lubricant composition provides protection against the transmission of HPV, including but not limited to HPV strains known to cause cancer, which may occur during male-female sexual encounters, male-male sexual encounters, and female-female sexual encounters. In still further embodiments, the antiviral lubricant composition can provide protection against the transmission of HPV between high-risk sexual partners, including those already infected with at least one strain of HPV.

In various embodiments, any of the antiviral lubricating compositions described herein can be contacted with the skin or epithelial tissue of one or more sexual partners, particularly the skin or epithelial tissue located on or inside at least one of the vagina, anus, mouth, or penis, before sexual intercourse to preventively inhibit the transmission of HPV from one sexual partner to another.In such embodiments, the antiviral lubricating composition can be contacted with the skin of one or more sexual partners less than 8 hours, such as less than 4 hours, less than 2 hours, less than 1 hour, less than 30 minutes, less than 15 minutes, less than 5 minutes, less than 1 minute, or less than 30 seconds to less than 1 second before sexual intercourse.In other embodiments, the antiviral lubricating composition can be contacted with the skin or epithelial tissue of one or more sexual partners, particularly the skin or epithelial tissue located on or inside at least one of the vagina, anus, mouth, or penis, after sexual intercourse to reduce the spread of HPV from cell to cell after HPV is transmitted. In such embodiments, the antiviral lubricating composition may be contacted with the skin or epithelial tissue of one or more sexual partners within 8 hours after sexual intercourse, e.g., within 4 hours, within 2 hours, within 1 hour, within 30 minutes, within 15 minutes, within 5 minutes, within 1 minute, or within 30 seconds, and up to 1 second after sexual intercourse.

In various embodiments, the antiviral lubricating composition made by the method of the present invention can be applied to human skin or epithelial tissues independent of sexual activity. In some embodiments, the antiviral lubricating composition can be applied to reduce, inhibit, or ameliorate the transmission or effects of non-sexually transmitted viruses, including but not limited to coronaviruses, reoviruses, adenoviruses, orthomyxoviruses, paramyxoviruses, pneumoviruses, picornaviruses, and non-sexually transmitted retroviruses and herpes viruses. Non-limiting examples of diseases caused by such viruses include but are not limited to severe acute respiratory disease (SARS), COVID-19, influenza, measles, mumps, chickenpox, enteroviruses, rhinoviruses, polio, adenoviruses, and rotaviruses. In some embodiments, the antiviral lubricating composition can be applied to animals with infections from diseases caused by viruses caused by any of the above virus families or types. Methods and substrates for applying the antiviral lubricating composition to help treat or reduce the effects of such conditions in humans or animals are described in more detail below.

In other embodiments, the antiviral lubricant compositions can be utilized in conjunction with feminine hygiene products for purposes including, but not limited to, as vaginal moisturizers, vaginal deodorants, and vaginal odor eliminators.

In another embodiment, the antiviral lubricant composition is a non-Newtonian pseudoplastic fluid that undergoes thixotropic shear thinning, which further reduces the viscosity of the composition in response to mechanical strain. By way of non-limiting example, such mechanical strain may occur when one, two or more people engage in sexual activity, including sexual activity with a male and a female sexual partner, two or more male sexual partners, two or more female sexual partners, and combinations thereof.

In another embodiment, the antiviral lubricating composition has a rheological profile that allows the lubricity of the dried antiviral lubricating composition on the skin to be maintained upon addition of water or other bodily fluids to the dried antiviral lubricating composition. Non-limiting examples of bodily fluids include saliva and vaginal secretions or discharges. In a further embodiment, upon addition of water or bodily fluids to the dried antiviral lubricating composition, the antiviral lubricating composition retains its antiviral activity, including against HPV.

In various embodiments, the antiviral lubricating composition of the present invention can be prepared substantially free of ingredients typically utilized in commercially available personal lubricants, including, but not limited to, oils, particularly silicone oils; cellulose; and polyquaterniums. In various embodiments, the antiviral lubricating composition can be prepared substantially free of spermicides, such as nonoxynol-9, which are also often present in commercially available personal lubricants. However, in other embodiments, the antiviral lubricating composition can be prepared to include oils, cellulose, polyquaterniums, and/or nonoxynol-9.

In another embodiment, a method of forming the antiviral lubricating composition of the present invention can include the steps of: (a) providing a carrageenan powder having carrageenan, the carrageenan having at least 80% by weight lambda-carrageenan and up to 10% by weight of a secondary carrageenan selected from the group consisting of iota-carrageenan and kappa-carrageenan and combinations thereof, preferably 10% by weight kappa-carrageenan; (b) combining the carrageenan powder with an aqueous solution having a quantity of a polyol while mixing to form a carrageenan aqueous suspension; (c) heating the carrageenan aqueous suspension to a temperature of at least 60° C.; (d) mixing for a time sufficient to convert the heated carrageenan aqueous suspension into a homogenous aqueous solution; (e) cooling the homogenous aqueous solution to a temperature of less than 50° C.; and (f) mixing one or more pH adjusters with the cooled homogenous aqueous solution, thereby forming the antiviral lubricating composition.

In various embodiments, the carrageenan suspension is cloudy. When substantially all of the polysaccharides in the carrageenan suspension are homogenized by heating and mixing, the carrageenan suspension becomes transparent and the resulting homogeneous solution becomes translucent. In another embodiment, the antiviral carrageenan suspension becomes transparent upon formation of the homogeneous solution and remains transparent. In another embodiment, there are substantially no visible particulates, aggregates, or flocculants in the antiviral lubricating composition.

In various embodiments, the turbidity of any of the mixtures, suspensions, or antiviral lubricant compositions disclosed herein is measured using a turbidity scale, such as Formazin Nephelometric Units (FNU), Jackson Turbidity Units (JTMU), or the like. The turbidity of the suspension may be quantitatively described based on the method of measuring the concentration of suspended particles in a sample, which may include, but is not limited to, units (JTU) and nephelometric turbidity units (NTU). In another embodiment, the turbidity of any of the mixtures, suspensions, or antiviral lubricant compositions described herein is characterized as a function of NTU. In another embodiment, the turbidity of the carrageenan suspension upon addition of carrageenan to an aqueous solution is at least 100 NTU, including at least 200 NTU, 300 NTU, 400 NTU, 500 NTU, 600 NTU, 700 NTU, 800 NTU, 900 NTU, 1000 NTU, 2000 NTU, or 3000 NTU, up to at least 4000 NTU. In another embodiment, the turbidity of the homogenized antiviral lubricating composition is less than 25 NTU, less than 20 NTU, less than 15 NTU, less than 10 NTU, less than 8 NTU, less than 6 NTU, less than 5 NTU, less than 4 NTU, less than 3 NTU, or less than 2 NTU, to less than 1 NTU, preferably less than 5 NTU, and more preferably about the same as the turbidity of drinking water.

In various embodiments, the step of combining the carrageenan powder with the aqueous solution while mixing includes the substeps of (A): mixing the carrageenan powder with the polyol for a time sufficient to form a wet carrageenan mixture, and (B) combining the wet carrageenan mixture with the aqueous solution while mixing for a time sufficient to form a carrageenan aqueous suspension. In various embodiments, the weight ratio of polyol to carrageenan in the wet carrageenan mixture is at least 1:10, and is at least 1:5, 1:1, 2:1, 4:1, 6:1, 8:1, 10:1, 20:1, 30:1, or 40:1, including at least 50:1. In further embodiments, the weight ratio of polyol to carrageenan is between 1:1 and 10:1. In various embodiments, the weight ratio of the wet carrageenan mixture to be combined with the aqueous solution to form the carrageenan suspension is between 3:1 and 60:1. In still further embodiments, the weight ratio of the aqueous solution to form the carrageenan suspension and the wet carrageenan mixture to be mixed is from 8:1 to 45:1.

In various embodiments, the step of mixing the wet carrageenan mixture with the aqueous solution comprises dispersing the carrageenan contained in the wet carrageenan mixture within the aqueous solution. In further embodiments, the dispersing step comprises thoroughly shear mixing the carrageenan powder with the polyol using a dispersing mixer for a time sufficient to homogenize the carrageenan in the aqueous solution while minimizing scission of the intramolecular bonds between the sugar residues within each carrageenan polysaccharide.

In various embodiments, one or more of the wet carrageenan mixture, the carrageenan aqueous suspension, and/or the antiviral lubricant composition are heated to a temperature of at least 60°C, such as at least 65°C, 70°C, 75°C, 80°C, 85°C, or 90°C, and optionally to at least 95°C. In various embodiments, the carrageenan aqueous suspension is heated to at least 70°C and up to 75°C.

In various embodiments, the step of mixing other powder, solid, or liquid adjuvants into the aqueous solution comprises stirring the adjuvant in the aqueous solution under sufficient shear mixing for a sufficient time to form a compositionally homogenous solution.

In various embodiments, the carrageenan powder comprising lambda-carrageenan is a dried extract from seaweed, particularly the red seaweed Chondrus crispus. In various embodiments, lambda-carrageenan comprises at least 80% by weight of the seaweed extract, such as at least 85%, 90%, or 95% by weight. In various embodiments, lambda-carrageenan comprises up to 100% by weight of the seaweed extract, such as up to 95%, 90%, or 85% by weight. In various embodiments, lambda-carrageenan comprises 90% by weight of the seaweed extract.

In various embodiments, the carrageenan powder consists solely of carrageenan in powder form. In another embodiment, the carrageenan powder consists essentially solely of carrageenan in powder form.

In various embodiments, the carrageenan powder can have carrageenan in powder form and additional powder ingredients, non-limiting examples of which can include pH adjusters, disinfectants, preservatives, sweeteners, and salts, all of which are described in further detail below.

In various embodiments, within the carrageenan powder having lambda-carrageenan, the remaining carrageenan species can comprise kappa-carrageenan, iota-carrageenan, or a combination of kappa-carrageenan and iota-carrageenan. In various embodiments, either or both of the kappa-carrageenan and iota-carrageenan can comprise up to 20% by weight of the carrageenan powder, such as up to 15%, 10%, 8%, 6%, 4%, 2%, or 1% by weight of the carrageenan powder. In various embodiments, when present, the kappa-carrageenan and iota-carrageenan together comprise at least 1% by weight of the carrageenan powder, such as 2%, 4%, 6%, 8%, or 10%, and up to at least 15% by weight. In various embodiments, lambda-carrageenan can comprise 90% by weight of the carrageenan powder, and kappa-carrageenan and iota-carrageenan together comprise 10% by weight of the carrageenan powder. In various embodiments, lambda-carrageenan can comprise 90% by weight of the carrageenan powder, and kappa-carrageenan comprises 10% by weight of the carrageenan powder. In various embodiments, lambda-carrageenan can comprise 90% by weight of the carrageenan powder, and lambda-carrageenan comprises 10% by weight of the carrageenan powder.

In various embodiments, the antiviral lubricating composition has at least 0.001% by weight of carrageenan, such as at least 0.01%, 0.1%, 0.5%, 0.75%, 1.0%, 1.2%, 1.4%, 1.6%, 1.8%, 2.0%, 2.2%, 2.4%, 2.5%, or 3% by weight, and optionally up to at least 5% by weight. In other embodiments, the antiviral lubricating composition has less than 5 wt. % carrageenan, e.g., less than 3 wt. %, less than 2.5 wt. %, less than 2.4 wt. %, less than 2.2 wt. %, less than 2 wt. %, less than 1.8 wt. %, less than 1.6 wt. %, less than 1.4 wt. %, less than 1.2 wt. %, less than 1.0 wt. %, less than 0.75 wt. %, less than 0.5 wt. %, less than 0.1 wt. %, less than 0.01 wt. %, or less than 0.001 wt. %. In further embodiments, the antiviral lubricating composition has from 0.2 wt. % to 2.3 wt. % carrageenan. In yet further embodiments, the antiviral lubricating composition has from 0.8 wt. % to 2 wt. % carrageenan. In still further embodiments, the antiviral lubricating composition has from 1.5 wt. % to 1.7 wt. % carrageenan.

In various embodiments, the addition of one or more polyols to the carrageenan powder partially loosens the carrageenan polysaccharides in the powder, making additional polarizable contacts available for interaction upon addition of an aqueous solution. In other embodiments, the presence of a polyol in the antiviral lubricating composition enhances the sensation, tactility, and/or lubricity experienced by the wearer or his/her partner during sexual activity. In further embodiments, the at least one polyol can be selected from the group consisting of glycerol; propylene glycol (1,2-propanediol); 1,3-propanediol; 1,3-butanediol; 1,4-butanediol; 2,3-butanediol; xylitol; sorbitol; erythritol; isomalt; lactitol; maltitol; mannitol; polyethylene glycol; and polypropylene glycol; and combinations thereof. In yet further embodiments, the antiviral lubricating composition has less than 50 wt% of the antiviral lubricating composition polyol, such as less than 25 wt%, less than 15 wt%, less than 10 wt%, less than 9 wt%, less than 8 wt%, less than 7 wt%, less than 6 wt%, less than 5 wt%, less than 4 wt%, less than 3 wt%, less than 2 wt%, less than 1 wt%, less than 0.5 wt%, or less than 0.1 wt%. In other embodiments, the antiviral lubricating composition has at least 0.1 wt% of the polyol, such as at least 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 15 wt%, 25 wt%, or 35 wt% of the polyol. In yet further embodiments, the antiviral lubricating composition has less than 10 wt% of the polyol. In yet still further embodiments, the antiviral lubricating composition has between 0.5 wt% and 5 wt% of the polyol. In still further embodiments, the antiviral lubricant composition has 4% to 4.5% by weight of polyol. In some embodiments, the polyol is propylene glycol. In some embodiments, the polyol is 1,3-propanediol.

In various embodiments, the antiviral lubricating composition is an injectable composition having a viscosity of less than 10,000 cP, such as less than 8,000 cP, less than 6,000 cP, less than 5,000 cP, less than 4,000 cP, less than 3,000 cP, less than 2,000 cP, or less than 1,000 cP. In other embodiments, the antiviral lubricating composition has a viscosity of at least 500 cP, such as at least 1,000 cP, 2,000 cP, 3,000 cP, 4,000 cP, 5,000 cP, 6,0000 cP, or 8,000 cP. In further embodiments, the antiviral lubricating composition has a viscosity of between 500 cP and 8,000 cP, more particularly between 1,000 cP and 4,000 cP, and even more particularly between 2,000 cP and 3,000 cP. In some embodiments, the antiviral lubricating composition has a viscosity of 1,500 cP to 2,500 cP. In some embodiments, the antiviral lubricating composition has a viscosity of 2,000 cP.

In various embodiments, the antiviral lubricating composition has a viscosity that allows it to be poured from an open container, but remains on an inclined, slanted, curved, or inversely curved surface when applied. Non-limiting examples of surfaces include skin or epithelial tissues such as the cervix, vulva, vagina, clitoris, penis, anus, nose, nasal cavity, mouth, and throat. Other non-limiting examples of surfaces to which the antiviral lubricating composition can be applied include sexual accessories or devices such as sex toys, vibrators, rings, or beads, or internal applicators such as swabs; elongate sticks or rods, wearable inserts, injectors, syringes, cannulas, pipettes, etc.

In various embodiments, the viscosity of the antiviral lubricating composition decreases in a non-Newtonian manner when one or more shear forces are applied to the surface containing the antiviral lubricating composition or the surface is used, as is commonly applied during sexual activity.In further embodiments, the viscosity decreases to less than 5,000 cP, such as less than 4,000 cP, less than 3,000 cP, less than 2,500 cP, less than 2,000 cP, less than 1,500 cP, less than 1,000 cP, less than 800 cP, less than 600 cP, less than 500 cP, less than 400 cP, or less than 300 cP, and optionally less than 200 cP.In other embodiments, the lubricity of the antiviral lubricating composition is maintained when continuously subjected to shear forces for at least 15 seconds, such as at least 30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, or 45 minutes, and optionally up to at least 1 hour.

In various embodiments, increasing the total concentration of carrageenan in the antiviral lubricating composition exponentially increases the viscosity of the composition. In a further embodiment, the relative concentrations of kappa, iota, and lambda forms of carrageenan affect the exponential growth rate of the viscosity of the antiviral lubricating composition differently. In yet a further embodiment, the antiviral lubricating composition has 90% lambda-carrageenan and 10% of either or both of kappa-carrageenan or iota-carrageenan. In yet another embodiment, the antiviral lubricating composition has 90% lambda-carrageenan and 10% kappa-carrageenan. In yet a further embodiment, the antiviral lubricating composition has 90% lambda-carrageenan and 10% iota-carrageenan.

In various embodiments, the type of mixing rotor and mixing speed can be optimized to control the viscosity of the resulting antiviral lubricating composition. In some embodiments, mixing is performed under shear conditions sufficient to homogenize the carrageenan-containing composition while maintaining the length of each carrageenan polysaccharide and maintaining its lubricity before applying the composition to skin or epithelial tissue, particularly before or during sexual activity.

In various embodiments, the device for carrying out the mixing step of the present invention, including the stirring step or the dispersing step, can have any conventional mixing device for the intended use. One non-limiting example of a mixing device is a paddle mixer. One example of a paddle mixer is a mixer with at least one folding impeller blade. One specific example of a paddle mixer is a Mixer Direct R-AD665 industrial gallon paddle mixer with two folding impeller blades. In still further embodiments, a paddle mixer is used for each of the mixing steps to form the antiviral lubricant composition. In other still further embodiments, each mixing step is carried out in a low-speed mixer operating at a rotation speed of 500 revolutions per minute (RPM) or less. In still further embodiments, the mixing of the antiviral lubricant composition after homogenizing the carrageenan in the aqueous solution can be carried out at a speed of 250 RPM or less.

In various embodiments, the antiviral lubricating composition formed by the method of the present invention has an osmolality that allows the skin or epithelial tissue, particularly the epithelial tissue in the vagina or rectum, to maintain a healthy plasma water electrolyte balance. In further embodiments, the antiviral lubricating composition has an osmolality of less than 1200 mOsmol/kg, such as less than 1000 mOsmol/kg, less than 900 mOsmol/kg, less than 800 mOsmol/kg, less than 700 mOsmol/kg, less than 600 mOsmol/kg, less than 500 mOsmol/kg, less than 400 mOsmol/kg, less than 300 mOsmol/kg, or less than 200 mOsmol/kg, and optionally less than 100 mOsmol/kg. In yet further embodiments, the antiviral lubricating composition has an osmolality of between 650 mOsmol/kg and 800 mOsmol/kg. In yet another yet further embodiment, the osmolality of the antiviral lubricating composition is isotonic with the normal osmolality of human semen, between 250 mOsmol/kg and 380 mOsmol/kg, and in yet a further embodiment, the osmolality of the antiviral lubricating composition is isotonic with the normal osmolality of vaginal secretions, between 260 mOsmol/kg and 290 mOsmol/kg.

In various embodiments, the antiviral lubricating composition of the present invention can further comprise one or more pH adjusters comprising an acid, particularly an organic acid, more particularly citric acid. In other embodiments, the one or more pH adjusters can comprise a weak acid and its conjugate base to form a buffer. As a non-limiting example, the addition of citrate to the antiviral lubricating composition can be achieved by adding both citric acid and a citrate salt, such as sodium citrate or magnesium citrate.

In various embodiments, the pH of the antiviral lubricating composition is less than 9.0, such as less than 8.0, less than 7.0, less than 6.5, less than 6.0, less than 5.5, less than 5.0, less than 4.5, or less than 4.0, and optionally less than 3.5. In other further embodiments, the pH of the antiviral lubricating composition is at least 3.5, such as at least 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, or 8.0, and optionally at least 9.0. In still further embodiments, the pH of the antiviral lubricating composition is between 5.5 and 7.0. In still further embodiments, the pH of the antiviral lubricating composition can be optimized for application directly to the vagina or for contact with the vagina during sexual activity. In such embodiments, the pH of the antiviral lubricating composition is between 3.5 and 5.5, and in particular 4.5.

In various embodiments, the pH of the antiviral lubricating composition is adjusted after the carrageenan is homogenized and the resulting antiviral lubricating composition is cooled. In further embodiments, the antiviral lubricating composition can be cooled to less than 50° C., such as less than 45° C., less than 40° C., less than 35° C., less than 30° C., or less than 25° C., optionally less than 20° C. In still further embodiments, the antiviral lubricating composition is cooled to less than 30° C. before adjusting the pH of the composition.

In various embodiments, the concentration of one or more pH adjusters in the pH adjusted antiviral lubricating composition is less than 1% by weight of the antiviral lubricating composition, such as less than 0.5% by weight, less than 0.25% by weight, less than 0.1% by weight, or less than 0.05% by weight, optionally less than 0.01% by weight of the antiviral lubricating composition. In further embodiments, the concentration of one or more pH adjusters in the pH adjusted antiviral lubricating composition is 0.1% by weight or less. In yet further embodiments, the concentration of one or more pH adjusters in the pH adjusted antiviral lubricating composition is 0.05% by weight or less. The pH adjusters can be added to the composition as a component of the carrageenan powder to which the polyol is added, to the carrageenan suspension, or to the antiviral lubricating composition after the carrageenan is homogenized.

In various embodiments, the method of forming the antiviral lubricant composition can further include mixing one or more sweeteners and/or one or more preservatives into either the carrageenan powder, the carrageenan aqueous suspension, or the cooled homogenous aqueous solution. In various embodiments, one or more sweeteners are added to the carrageenan aqueous suspension. In various embodiments, one or more preservatives are added to the homogenous aqueous solution along with one or more pH adjusters. In various embodiments, each of the above sweeteners and preservatives, as well as additional ingredients such as salts and/or flavorings, can be included in the antiviral lubricant composition to supplement its antiviral activity, aid application to skin or epithelial tissue, and/or enhance its performance during sexual activity.

In various embodiments, the antiviral lubricating compositions of the present invention can further comprise one or more sweeteners, particularly saccharin, at 0.01% to 1% by weight of the antiviral lubricating composition, particularly 0.1% to 0.5% by weight of the antiviral lubricating composition. In another embodiment, the concentration of saccharin in the antiviral lubricating composition is up to 0.5% by weight. In another embodiment, the concentration of saccharin in the antiviral lubricating composition is 0.125% by weight.

In various embodiments, saccharin can be added to the carrageenan mixture or suspension as an aliquot from a concentrated stock solution. In further embodiments, the total weight of the saccharin stock solution added to the carrageenan mixture or antiviral lubricating composition comprises 1% to 10% by weight of the finished antiviral lubricating composition. In yet further embodiments, the saccharin stock solution is 2.5% by weight saccharin in water. In yet further embodiments, the amount of 2.5% by weight saccharin stock solution added to the carrageenan mixture is equal to 5% by weight of the antiviral lubricating composition, with the final concentration of saccharin in the antiviral lubricating composition being 0.125% by weight. In yet still further embodiments, the saccharin is provided as sodium saccharin.

In various embodiments, the antiviral lubricating compositions of the present invention can further comprise one or more preservatives, particularly from 0.01% to 1.0% by weight of one or more preservatives selected from the group consisting of 2-phenoxylethanol, chlorphenesin, and sodium dehydroacetate, and combinations thereof.

In various embodiments, the antiviral lubricating composition of the present invention can optionally further comprise one or more fragrances designed to impart a pleasant fragrance effect to the composition. The fragrances can include essential oils, or component compounds within essential oils that can impart an odor. Non-limiting examples of fragrances that can be provided by such fragrances can include citrus, lemon, berry, or peppermint fragrances. In certain embodiments, the fragrances can comprise 0.01% to 5% by weight of the antiviral lubricating composition, particularly 0.1% to 2.5% by weight of the antiviral lubricating composition.

In various embodiments, the antiviral lubricating composition of the present invention can further comprise a salt, particularly a sodium salt or a zinc salt, more particularly a zinc salt, which can be used to increase the ionic strength of the composition while supporting or complementing either or both of the rheological properties or the antiviral activity of the composition. The salt can be added to the composition as a component of the carrageenan powder to which the polyol is added, to the carrageenan suspension, or to the antiviral lubricating composition after the carrageenan has been homogenized.

In various embodiments, the process for forming the homogenized antiviral lubricating composition of the present invention can be completed in less than 12 hours, e.g., less than 10 hours, less than 8 hours, less than 6 hours, less than 4 hours, or less than 3 hours, and optionally less than 2.5 hours. In further embodiments, the process for forming the homogenized antiviral lubricating composition of the present invention is completed in 2-3 hours.

In another embodiment, a method of forming an antiviral lubricating composition can include the steps of: (a) providing a carrageenan powder having carrageenan, the carrageenan having 90% by weight lambda-carrageenan and 10% by weight kappa-carrageenan; (b) combining the carrageenan powder with an aqueous solution comprising propylene glycol while mixing to form a carrageenan aqueous suspension; (c) adding one or more sweeteners to the carrageenan aqueous suspension; (d) heating the carrageenan aqueous suspension to a temperature of at least 70°C and up to 75°C; (e) mixing the heated carrageenan aqueous suspension for a sufficient time to form a homogenous aqueous solution; (f) cooling the homogenous aqueous solution to a temperature of less than 30°C; and (g) mixing one or more pH adjusters and one or more preservatives into the cooled homogenous aqueous solution sufficient to adjust the pH of the antiviral lubricating composition to between 3.5 and 7.0, thereby forming the antiviral lubricating composition. In another aspect, the antiviral lubricating composition formed by the method can consist essentially of 1.5% to 1.7% by weight carrageenan, 4.0% to 4.5% by weight propylene glycol, up to 0.5% by weight one or more sweeteners, up to 1% by weight one or more preservatives, and 0.01% to 1% by weight one or more pH adjusters, with the balance being water. In a further aspect, the antiviral lubricating composition formed by the method can be translucent, have a viscosity of at least 2,000 cP and up to 3,000 cP, and a turbidity of 25 NTU or less, preferably 5 NTU or less. In yet a further aspect, the antiviral lubricating composition formed by the method can have an osmolality ranging from at least 650 mOsmol/kg to 850 mOsmol/kg. In yet a further aspect, the pH of the antiviral lubricating composition formed by the method is 3.5 to 5.5. In other yet further embodiments, the pH of the antiviral lubricant composition formed by the above method is between 5.5 and 7.0. In even further embodiments, the antiviral lubricant composition formed by the above method is effective to reduce, inhibit, or ameliorate transmission of HPV. In other even further embodiments, the antiviral lubricant composition formed by the above method is effective to reduce, inhibit, or ameliorate transmission of COVID-19.

In another embodiment, a method of forming the antiviral lubricating composition of the present invention includes the steps of: (a) providing a carrageenan powder having carrageenan, the carrageenan having 90% by weight lambda-carrageenan and up to 10% by weight kappa-carrageenan; (b) mixing the carrageenan powder with a polyol, the carrageenan powder and the polyol being stirred or agitated for a sufficient time to form a wet carrageenan mixture, the weight ratio of glycol to carrageenan being 1:1 to 10:1; (c) dispersing the wet carrageenan mixture in an aqueous solution under shear mixing for a sufficient time to form a cloudy carrageenan suspension, the weight ratio of aqueous solution to carrageenan being 45:1 to 8:1; (d) adding one or more sweeteners to the cloudy carrageenan suspension while stirring the cloudy carrageenan suspension, the sweeteners comprising up to 0.5% by weight of the finished antiviral lubricating composition; (e) shearing the cloudy carrageenan suspension for a sufficient time, including up to 100 minutes. (f) cooling the homogenized antiviral lubricant composition until the temperature of the antiviral lubricant composition is less than 30°C; (g) adding one or more pH adjusters to the cooled antiviral lubricant composition under stirring in an amount sufficient by weight to adjust the antiviral lubricant composition to a pH of 3.5 to 7.0; (h) adding up to 1% by weight of the antiviral lubricant composition of one or more pH adjusters. adding a preservative to the cloudy carrageenan suspension or to the cooled antiviral lubricating composition under stirring, wherein (i) the antiviral lubricating composition has 0.2% to 2.3% by weight of carrageenan and up to 10% by weight of polyol, (ii) the antiviral lubricating composition has a viscosity of less than 5,000 cP, (iii) the antiviral lubricating composition is translucent, and (iv) the antiviral lubricating composition is effective in reducing, inhibiting, or ameliorating human papillomavirus (HPV) transmission. In a further embodiment, the antiviral lubricating composition has 1.5% to 1.7% by weight of carrageenan, 4% to 4.5% by weight of 1,2- propanediol , a viscosity of 2,000 cP to 3,000 cP, an osmolality of 650 mOsmol/kg to 850 mOsmol/kg, and a pH of 6.25 to 6.75. In yet further embodiments, the carrageenan has 90% by weight lambda-carrageenan and about 10% by weight kappa-carrageenan. In yet still further embodiments, the antiviral lubricant composition formed by the above method is effective in reducing, inhibiting, or ameliorating the transmission of HPV. In other yet still further embodiments, the antiviral lubricant composition formed by the above method is effective in reducing, inhibiting, or ameliorating the transmission of COVID-19.

In another aspect, the present invention also describes a method for reducing, inhibiting, or ameliorating the transmission, symptoms, or effects of a viral infection, comprising: (a) providing any of the above-mentioned antiviral lubricating compositions; (b) contacting the antiviral lubricating composition with the skin or epithelial tissue of one or more partners. Non-limiting examples of skin or epithelial tissue to which the antiviral lubricating composition can be applied include the skin, cervix, vulva, vagina, clitoris, penis, anus, nose, nasal cavity, mouth, and throat. In another embodiment, the antiviral lubricating composition can be applied to any skin or epithelial tissue, internal or external, where viral infection is known to exist.

In various embodiments, a method of reducing, inhibiting, or ameliorating the transmission, symptoms, or effects of a viral infection can include the steps of: (a) providing a substrate having one or more skin-contacting surfaces, the substrate configured to contact skin or epithelial tissue and/or be inserted into one or more body cavities; (b) lubricating one or more skin-contacting surfaces of the substrate with an antiviral lubricating composition, thereby producing a lubricated substrate; (c) contacting the lubricated substrate with skin or epithelial tissue; and (d) transferring the antiviral lubricating composition from the lubricated substrate to the skin or epithelial tissue.

In various embodiments, a method for reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between two or more partners engaged in sexual activity can include the steps of (a) providing any of the above-mentioned antiviral lubricating compositions; and (b) contacting the antiviral lubricating composition with the skin or epithelial tissue of one or more partners, where the skin or epithelial tissue is at least one of the vagina, anus, mouth, and penis. In a further embodiment, at least one partner is male and at least one partner is female. In another further embodiment, at least two partners are male. In yet another further embodiment, at least two partners are female. In yet another embodiment, there are three or more sexual partners, consisting of any combination of males or females.

In various embodiments, a method of reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexually engaged partners can include the steps of: (a) providing a substrate comprising one or more skin-contacting surfaces, the substrate configured for insertion into one or more body cavities selected from the group consisting of the vagina, the mouth, or the anus; (b) lubricating one or more skin-contacting surfaces of the substrate with an antiviral lubricating composition, thereby producing a lubricated substrate; (c) contacting the lubricated substrate with skin or epithelial tissue located on or within at least one of the vagina, anus, mouth, or penis of one or more partners; and (d) transferring the antiviral lubricating composition from the lubricated substrate to the skin or epithelial tissue.

In various embodiments, the substrate is a condom. In further embodiments, the condom comprises latex. In other further embodiments, the condom comprises polyurethane and/or other synthetic materials. In still other further embodiments, the condom is incompatible with oil-based personal lubricants. In yet other embodiments, the condom is selected from the group consisting of male condoms and female condoms.

In various embodiments in which a condom is the substrate, a method for reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexually engaged partners further comprises the steps of lubricating the skin-contacting surface of the condom; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more partners with the lubricated skin-contacting surface of the condom; and transferring an anti-viral lubricating composition from the lubricated skin-contacting surface of the condom to the skin or epithelial tissue.

In various embodiments in which a condom is the substrate, a method of reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexually engaged partners further comprises the steps of placing a condom on the finger or penis of one partner; lubricating the exterior surface of the condom with an antiviral lubricating composition; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners with the lubricated exterior surface of the condom; and transferring the antiviral lubricating composition from the lubricated exterior surface of the condom to the skin or epithelial tissue.

In various embodiments in which a condom is the substrate, the method for reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexually engaged partners further comprises the steps of lubricating the condom; sealing the lubricated condom in a package; storing the lubricated condom in the package; removing the lubricated condom from the package; applying the lubricated condom to the finger or penis of one of the sexual partners; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners with the lubricated condom; and transferring an antiviral lubricating composition from the lubricated condom to the skin or epithelial tissue.

In various embodiments, the substrate is a sexual accessory device, including, but not limited to, a sex toy, a dildo, a vibrator, a ring, or beads. In further embodiments, the method further comprises sealing the sexual accessory device in a package, storing the lubricated sexual accessory device in the packaging, and removing the lubricated sexual accessory device from the package prior to contacting the skin or epithelial tissue of one or more partners. The antiviral lubricating composition can be applied to any skin-contacting surface of the sexual accessory device, typically prior to contacting the skin of one or more sexual partners, particularly prior to insertion into the vagina, anus, or mouth.

In various embodiments, a condom lubricated with any of the antiviral lubricating compositions of the present invention can be applied to an unlubricated sexual accessory device to provide lubrication for use during sexual activity. In other embodiments, a unlubricated condom can be applied to a sexual accessory device lubricated with any of the antiviral lubricating compositions of the present invention. In yet other embodiments, a unlubricated condom can be applied to an unlubricated sexual accessory device and then lubricated with any of the antiviral lubricating compositions of the present invention.

In various aspects, the substrate is an internal applicator configured for insertion into the vagina, rectum, mouth, or nose, the internal applicator being selected from the group consisting of a swab, an elongated stick or rod, a wearable device, an injector, a syringe, a cannula, or a pipette. In further aspects, the internal applicator comprises a skin contacting surface configured for contacting epithelial tissue within a human body cavity, particularly within the vagina, nose, mouth, or rectum. In other further aspects, the internal applicator has a reservoir configured to house or contain the antiviral lubricating composition prior to transferring the antiviral lubricating composition to epithelial tissue within a human body cavity, particularly within the vagina, nose, mouth, or rectum.

In various embodiments, the substrate is a swab of sufficient length to be inserted into the mouth or nose to contact epithelial tissue within the nasal or oral cavity, including the throat. In various embodiments, the lubricated swab can be inserted into the nose or mouth to contact epithelial tissue within the nasal or oral cavity to reduce, inhibit, or ameliorate the transmission, symptoms, or effects of viral respiratory infections, such as, but not limited to, SARS, COVID-19, Middle East Respiratory Syndrome (MERS), and adenovirus.

The present invention also provides kits for reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexually engaged partners, comprising an antiviral lubricating composition as described above and instructions describing any of the methods disclosed above for contacting the antiviral lubricating composition with the skin of one or more partners. The kits can further comprise any of the substrates described above, including condoms, sexual accessory devices, and/or internal applicators.

These and other aspects of the present invention will become apparent to those skilled in the art from the following detailed description.

<figref num="1">FIG. 1 shows a plot of the viscosity of the antiviral lubricant composition as a function of carrageenan concentration.</figref><figref num="2">FIG. 2 shows a plot of osmolality of the antiviral lubricating composition as a function of 1,2-propanediol concentration.</figref>

Detailed Description of the Invention

Although reference has been made to exemplary embodiments and specific terms have been used to describe them, it is understood that no limitation of the scope of the invention is intended. Further modifications of the methods described herein, as well as additional applications of the principles of the invention described, will occur to those skilled in the relevant art and possess this disclosure, but should be considered within the scope of the invention. Furthermore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this particular inventive aspect pertains. The terms used are intended only to describe those aspects, and unless so specified, the terms are not limiting. Headings are provided for convenience only and should not be construed as limiting the invention in any way. Furthermore, throughout the specification and claims, a given chemical formula or name is intended to encompass all optical isomers and stereoisomers, as well as racemic mixtures where such isomers and mixtures exist.

The present disclosure includes aqueous compositions that have antiviral activity against several different taxonomic families, including but not limited to Coronaviridae and/or Papillomaviridae, and can be utilized as personal lubricants during sexual activity. The antiviral lubricant compositions can be contacted with skin or epithelial tissues where viral infections are known to exist inside or outside the body, or areas that are commonly lubricated during sexual activity, including but not limited to the cervix, vulva, vagina, clitoris, penis, anus, nose, nasal passages, mouth, and throat. The antiviral lubricant compositions can reduce, inhibit, ameliorate, or prevent the transmission and/or persistence of sexually transmitted viruses, including human papillomavirus (HPV), human immunodeficiency virus (HIV), or herpes simplex virus (HSV), between sexual partners, including male-female, male-male, and female-female sexual partnerships.

Lambda-Carrageenan-Containing Compositions The antiviral activity of the antiviral lubricating compositions of the present invention is due to the presence of carrageenans, particularly lambda-carrageenans. Carrageenans are a collective term for a broad family of naturally occurring sulfated polysaccharides extracted from a wide range of seaweeds, particularly from Chondrus crispus, a red seaweed found on the Atlantic coast of the United States. The extracted carrageenans are usually obtained in one of ten forms that differ in terms of sulfate content, sulfate position within each polysaccharide, and acid/base properties. Three forms, kappa-carrageenan, iota-carrageenan, and lambda-carrageenan, are particularly common in compositions used in the food and pharmaceutical industries. The structures of kappa-carrageenan, iota-carrageenan, and lambda-carrageenan are shown below.

<img file="JP7635277B2_D0001.tif" />

As mentioned above, kappa-carrageenan, iota-carrageenan, and lambda-carrageenan contain repeating galactose units. In particular, kappa-carrageenan and iota-carrageenan have alternating units of D-galactose and 3,6-anhydro-galactose (3,6-AG), whereas lambda-carrageenan does not have 3,6-AG. Each type differs in the number of sulfate groups per disaccharide, with kappa-carrageenan, iota-carrageenan, and lambda-carrageenan having one, two, or three sulfate groups per alternating unit, respectively. As the number of sulfate groups in the polysaccharide increases, the ability of a particular type of carrageenan to form a gel decreases. Similarly, kappa-, iota-, and lambda-type carrageenans are all capable of solubilizing in aqueous solutions. However, the temperature at which a particular type becomes solubilized is also a function of the relative sulfate content. Thus, a pure sample of lambda-carrageenan can be solubilized in water at a lower temperature than a pure sample of kappa-carrageenan.

Carrageenans are commonly used in the food and pharmaceutical industries as thickening and/or gelling agents. When carrageenans are hydrated in an aqueous composition, they begin to swell, exponentially increasing the viscosity of the composition as a function of the total carrageenan concentration. However, the rate of exponential increase is inversely proportional to the sulfate content within each form of carrageenan, so kappa-carrageenan causes a greater exponential increase in viscosity than iota-carrageenan, which itself has a greater impact on viscosity than lambda-carrageenan. It should be noted that heated compositions with kappa-carrageenan and iota-carrageenan can form a gel network upon cooling, as the polysaccharides form a double helical quasicrystalline network, especially in the presence of cations. However, the presence of lambda-carrageenan in the composition partially inhibits gel formation, and in compositions most rich in lambda-carrageenan, gel formation is completely prevented. Without being bound to a particular theory, it is believed that the lack of 3,6-AG groups in lambda-carrageenan promotes gel inhibition.

Although the relative effects of kappa, iota, and lambda forms of carrageenan on the viscosity of a composition are known, the exponential growth rate of viscosity is generally not predictable from one composition to another, especially when the ratio of kappa, iota, and lambda-carrageenan varies from composition to composition. Also, the method of processing the carrageenan and other ingredients dramatically affects the viscosity of the resulting composition. Factors related to the viscosity of the final product include, but are not limited to, heating temperature, shear conditions, rotor type, mixing speed, mixing time, and additional ingredients that are also added to the composition. As a result, viscosity as a function of total carrageenan concentration can only be modeled when the ratio of each type of carrageenan is constant and the other processing steps are the same.

While carrageenan compositions containing primarily kappa and iota carrageenans are useful for thickening compositions or gels, they are inactive against HPV. On the other hand, lambda-carrageenan types have been shown to be effective in vitro (Buck, supra), It has been shown to be active against HPV both in vitro and in vivo (see, e.g., U.S. Pat. Nos. 5,208,031 and 8,367,098, and U.S. Patent Publication Nos. 2005/0171053, 2005/0239742, 2005/0261240, 2006/0127340, 2008/0227749, 2009/0088405, and 2011/0229446, the disclosures of which are incorporated by reference in their entireties). Without being bound to any particular theory, lambda-carrageenan utilizes a "lock and key" type mechanism whereby the polysaccharides attract the virus, interact with the viral capsid, and halt or prevent viral replication and inhibit viral activity, thereby significantly reducing the transmission and persistence of viruses, particularly HPV, in sexually active men and women.

In one study, sexually active women at high risk of contracting and/or transmitting HPV during sexual activity were given a gel containing lambda-carrageenan (see Marais, D., et al., (2011) Antiviral Therapy 16: 1219-1226, and U.S. Patent No. 8,367,098, the disclosures of which are incorporated by reference in their entirety). The composition tested, Carraguard®, has a 3% by weight mixture of kappa-carrageenan and lambda-carrageenan and a viscosity of 30,000-40,000 cP. Study participants were instructed to apply the gel in conjunction with vaginal intercourse. Over the course of the three-year study, the authors determined that among women with "relatively high compliance with gel use," those given the lambda-carrageenan-containing gel were only 62% likely to be classified as HPV positive.

However, as mentioned above, carrageenan (of any type) has historically been used as a thickening agent because it exponentially increases the viscosity of the composition, but is generally not preferred in personal lubricant formulations. In particular, gel compositions containing kappa-carrageenan and/or large amounts of iota-carrageenan are typically very viscous and tend to dry out quickly when applied to skin or epithelial tissue, causing the formation of sticky residues and loss of lubrication. As a result, most topical carrageenan-containing compositions, including those studied in Marais, et al., along with the related compositions of U.S. Pat. No. 8,367,098, are typically gels or creams. To put the viscosity of these carrageenan-containing compositions into context, the viscosity of Carraguard® compared to some common compositions is shown in Table 1 below.

<tables><img file="JP7635277B2_D0002.tif" /></tables>

The viscosity of the Carraguard® gel utilized in the Marais study ranges between that of chocolate and that of ketchup, as shown in Table 1. Although both chocolate and ketchup have shear thinning properties, and chocolate in particular may have an edible composition that can be utilized during sexual activity, the high viscosity of both compositions reduces their functionality as personal and sexual lubricants.

In contrast, compositions commonly used as personal lubricants that do not contain carrageenan are typically 5-10 times less viscous than the gels used in the Marais study and described in the '098 patent. Ideally, a personal lubricant composition should have a viscosity that allows it to be poured or gently squeezed from a container, remain on the skin after application, and produce shear thinning in response to stresses such as during sexual activity. Materials commonly found in personal lubricants include, but are not limited to, oils, especially silicone oils, gums, cellulose, glycerin, polyols, glycols, glycans, polyquaterniums, and other polymers. However, while these lubricants provide pleasurable results during sexual activity, they do not provide protection against HPV.

Another human in vivo study (see Magnan, et al., supra) investigated the use of a low viscosity personal composition containing lambda-carrageenan for anti-HPV activity. As in the Marais study, women were randomly assigned to receive either a placebo or a commercially available composition with lambda-carrageenan, Divine 9®, and were asked to apply the composition in conjunction with sexual activity. The test composition had 1.4% by weight of a carrageenan blend with lambda-carrageenan and iota-carrageenan, 37% by weight of propylene glycol, and had a viscosity of 1,000-4,000 cP (see Example 1, below). Although the Magnan study showed a similar reduction in HPV incidence to the Marais study, the presence of such a high concentration of propylene glycol caused the osmolality of the composition to exceed 5,000 mOsm/kg, a level that could potentially pose a risk to people using the composition and may increase the likelihood of contracting HPV in some people.

According to findings presented in the World Health Organization (WHO) report on sexual health ("Use and sourcing of additional lubricants for male and female condoms: WHO/UNFPA/FHI360 Advisory Note" World Health Organization, Geneva Switzerland, (2012) (see, incorporated by reference in its entirety), research has shown that lubricants with high osmolality may cause damage to the vaginal and anal epithelium and increase the risk of infection with HPV, HIV, and other sexually transmitted diseases. The WHO has also found that the main factor determining the osmolality of a particular personal lubricant is the presence of glycols within the composition. Glycols, also commonly known as "polyols," most commonly include glycerol, 1,2-propanediol, and 1,3-propanediol, and can disrupt the water-electrolyte balance within epithelial cells. The WHO has noted that most commercially available lubricants have an osmolality far exceeding that of normal vaginal secretions (260-290 mOsmol/kg) and semen (250-380 mOsmol/kg), and recommends that companies adjust the osmolality of commercially available personal lubricant compositions to 1,200 mOsmol/kg or less, aiming to be as isosmolar as possible to vaginal secretions and/or semen (between 250 and 400 mOsmol/kg).

The present invention provides several novel antiviral lubricant compositions that contain lambda-carrageenan, are active against viruses, including HPV, and have a viscosity similar to that of commercially available lubricants that do not contain carrageenan. In another embodiment, the antiviral lubricant composition has a rheological profile that allows the composition to retain its moisture and lubricity for several hours once applied, providing a pleasant experience for people engaged in sexual activity. In a further embodiment, the antiviral lubricant composition is a pseudoplastic non-Newtonian fluid composition that undergoes shear thinning in response to mechanical strain, especially during sexual activity. In yet a further embodiment, the antiviral lubricant composition of the present invention can be poured directly from the container without the need for squeezing or hand dispensing. In another yet further embodiment, the antiviral lubricant composition is substantially free of gel network.

As mentioned above, all types of carrageenan can be obtained from seaweed extracts, typically as a mixture of two, three or more types of carrageenan. The carrageenan mixture can be obtained as a raw extract or as a powder. In a further embodiment, the carrageenan utilized in the antiviral lubricant composition is obtained as a carrageenan powder. Non-limiting examples of commercially available carrageenan powders include Viscarin® PC109, Viscarin® PC209, Viscarin® PC515, Gelcarin® PC379, and Gelcarin® PC911. In yet a further embodiment, the carrageenan powder is Viscarin® PC209.

In another embodiment, the carrageenan powder has at least about 85% by weight lambda-carrageenan, including at least about 90% by weight lambda-carrageenan.

In another embodiment, the kappa-carrageenan and iota-carrageenan together can comprise up to about 20% by weight, including up to about 15%, 10%, 8%, 6%, 4%, 2%, or up to about 1% by weight of the carrageenan powder. In other embodiments, when present, the kappa-carrageenan and iota-carrageenan together can comprise at least about 1% by weight of the carrageenan powder and can comprise at least about 2%, 4%, 6%, 8%, or 10%, up to at least about 15% by weight of the carrageenan powder.

In another embodiment, the carrageenan powder has at least about 90% by weight lambda-carrageenan and up to about 10% by weight iota-carrageenan. In a further embodiment, the carrageenan powder has about 90% by weight lambda-carrageenan and about 10% by weight iota-carrageenan.

In another embodiment, the carrageenan powder has at least about 90% by weight lambda-carrageenan and up to about 10% by weight kappa-carrageenan. In a further embodiment, the carrageenan powder has about 90% by weight lambda-carrageenan and about 10% by weight kappa-carrageenan.

In another embodiment, the carrageenan mixture with lambda-carrageenan is substantially homogenized in the antiviral lubricating composition, and the majority of the carrageenan polysaccharides in the composition are present as free molecules in the aqueous solvent. In a further embodiment, the carrageenan mixture is completely homogenized in the antiviral lubricating composition. In some even further embodiments, the homogenous antiviral lubricating composition has a substantially uniform appearance and density. In other even further embodiments, the antiviral lubricating composition is a solution in which the ratio of carrageenan to solvent is substantially uniform. In still other even further embodiments, the antiviral lubricating composition is substantially free of particles, aggregates, clumps, or other solids visible to the naked eye and/or under a microscope at 10x magnification. In still further embodiments, the antiviral lubricating composition is translucent. In still yet further embodiments, the antiviral lubricating composition is transparent.

In another embodiment, the carrageenan comprises at least about 0.001% by weight of the antiviral lubricating composition, including at least about 0.01%, 0.1%, 0.5%, 1%, 2%, 2.5%, or 3% by weight to at least about 5% by weight of the antiviral lubricating composition. In a further embodiment, the carrageenan comprises from 0.5% to about 2.3% by weight of the antiviral lubricating composition. In yet a further embodiment, the carrageenan comprises from 0.8% to about 2.0% by weight of the antiviral lubricating composition. In yet a further embodiment, the carrageenan comprises from 1.5% to about 1.7% by weight of the antiviral lubricating composition.

Similarly, the viscosity, rheology, sensation, and overall performance of lambda-carrageenan-containing antiviral lubricating compositions can be controlled by adding small amounts of polymers, particularly polyols, to the antiviral lubricating compositions. As mentioned above, polyols are a class of compounds commonly found in commercial products as bulking agents, flavor retainers/masking agents, humectants, stabilizers, crystallization inhibitors, and for systemic and oral health benefits. Polyols are typically added to enhance the solubility of other polymers that may be present in commercial personal lubricant products, but polyols can be added in small amounts to the antiviral lubricating compositions of the present invention to reduce viscosity, reduce irritation, provide a secondary source of lubrication, and/or provide a stimulating "warmth" or "tingling" sensation that is often enjoyed by users during sexual activity.

Non-limiting examples of polyols that can be added include glycerol; propylene glycol (1,2-propanediol); 1,3-propanediol; 1,3-butanediol; 1,4-butanediol; 2,3-butanediol; xylitol; sorbitol; erythritol; isomalt; lactitol; maltitol; mannitol; polyethylene glycol; and polypropylene glycol; and combinations thereof. In general, the identity and concentration of the polyol(s) included in the antiviral lubricant composition can be controlled to obtain the desired properties. For example, mannitol and xylitol are regulated as food additives for special dietary needs, but polyols are otherwise "generally regarded as safe" (GRAS). Xylitol is also used in oral prophylaxis, and mannitol is used as a prophylactic for urinary tract infections. 1,3-butanediol, 1,4-butanediol, and 2,3-butanediol have been shown to reduce irritation in topical application of ointments, creams, and gel compositions. Sugar-based polyols can provide a certain sweetness, while maltitol can mimic the texture of fat in edible products.

In another embodiment, the polyol can comprise less than about 50% by weight of the antiviral lubricating composition, including less than about 25%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or 2% by weight of the antiviral lubricating composition, and can comprise less than about 1% by weight of the antiviral lubricating composition. In other further embodiments, the antiviral lubricating composition comprises at least about 1% by weight of the polyol, including at least about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, or 25% by weight, including at least about 35% by weight. In still further embodiments, the polyol comprises about to about 10% by weight of the antiviral lubricating composition.

In another embodiment, the polyol is propylene glycol (1,2-propanediol). In a further embodiment, the antiviral lubricating composition has up to 8% by weight of propylene glycol. In yet a further embodiment, the antiviral lubricating composition has 0.5% to about 5% by weight of propylene glycol. In yet a further embodiment, the antiviral lubricating composition has about 4% to about 5% by weight of propylene glycol. In an embodiment, the antiviral lubricating composition has about 4.0% to about 4.5% by weight of propylene glycol. In yet a further embodiment, the antiviral lubricating composition has about 2.0% to about 2.5% by weight of propylene glycol.

In another embodiment, the presence of polyols provides an antiviral lubricating composition superior to known personal lubricant compositions, since it maintains all of the sexual performance benefits of commercially available personal lubricants, while having the ability to inhibit HPV transmission and/or persistence. The antiviral lubricating composition is also thin enough to provide the tactile benefits of a personal lubricant composition, while being thick enough to remain on the skin or epithelial tissue, particularly the vagina, anus, penis, or mouth, prior to the initiation of sexual contact. In some embodiments, the personal lubricating composition has a viscosity of less than about 10,000 cP, less than about 8,000 cP, less than 6,000 cP, less than 4,000 cP, or less than 2,000 cP to less than about 1,000 cP. In other embodiments, the antiviral lubricating composition has a viscosity of at least about 500 cP, from at least about 1,000 cP, 2,000 cP, 4,000 cP, or 6,000 cP to at least about 8,000 cP. In further embodiments, the antiviral lubricating composition has a viscosity of about 500 cP to about 8,000 cP, particularly about 1,000 cP to about 4,000 cP, and more particularly about 2,000 cP to about 3,000 cP. In some embodiments, the antiviral lubricating composition has a viscosity of about 1,500 cP to 2,500 cP. In some embodiments, the antiviral lubricating composition has a viscosity of about 2,000 cP.

In another embodiment, the amount of polyol in the antiviral lubricating composition is limited to provide an osmolality within the level recommended by WHO. In another embodiment, the antiviral lubricating composition has an osmolality of less than about 1,200 mOsm/kg, less than about 1,000 mOsm/kg, less than 900 mOsm/kg, less than 800 mOsm/kg, less than 700 mOsm/kg, less than 600 mOsm/kg, less than 500 mOsm/kg, less than 400 mOsm/kg, less than 300 mOsm/kg, or less than 200 mOsmol/kg, to less than about 100 mOsmol/kg. In a further embodiment, the antiviral lubricating composition has an osmolality of about 250 to about 800 mOsmol/kg. In another further embodiment, the antiviral lubricating composition has an osmolality of about 650 to about 850 mOsmol/kg.

In another embodiment, the osmolality of the antiviral lubricating composition is isotonic with the osmolality of human plasma. In a further embodiment, the antiviral lubricating composition is isotonic with semen. In another further embodiment, the antiviral lubricating composition is isotonic with vaginal secretions. In yet another further embodiment, the antiviral lubricating composition has an osmolality of about 250 mOsmol/kg to about 400 mOsmol/kg.

Also, in another embodiment, some supplemental ingredients can be added to the antiviral lubricating composition to complement the antiviral activity of the composition and/or enhance the performance of the composition during sex. In some embodiments, the pH of the antiviral lubricating composition can be controlled by adding a pH adjuster. When carrageenan is solubilized in water, the pH of the composition is typically about 7-9. However, the effectiveness of the antiviral lubricating composition can be complemented by controlling the pH of the composition to match or resemble the target surface to which the composition is applied. For example, the pH of a healthy vagina is usually in the range of about 3.5 to about 5.5, while the pH of other epithelial cells, including those located in the rectum, is closer to neutral pH. Thus, in some embodiments, the pH adjuster is an acid that can lower the pH to a range complementary to the intended epithelial surface, particularly a pH of less than about 8.0, including less than about 7.0, less than 6.5, less than 6.0, less than 5.5, less than 5.0, less than 4.5, or less than 4.0, including less than about 3.5. In other embodiments, the pH of the antiviral lubricating composition is at least about 3.5, including at least about 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, or 7.0, up to at least about 8.0. In further embodiments, the pH of the antiviral lubricating composition is about 3.5 to about 5.5, particularly about 4.5. In other further embodiments, the pH of the antiviral lubricating composition is about 5.5 to about 7.0. In yet other further embodiments, the pH of the antiviral lubricating composition is about 6.25 to about 6.75.

In some embodiments, the pH adjuster is a strong acid, including but not limited to hydrochloric acid or sulfuric acid. However, in other embodiments, the pH adjuster is a weak acid to create a buffered antiviral lubricating composition. The weak acid can be selected based on buffering capacity, pKa, and availability. Non-limiting examples of weak acids that can be utilized as pH adjusters include citric acid, lactic acid, and acetic acid. In further embodiments, the antiviral lubricating composition has a pH adjuster of about 0.01% to about 1.0% by weight, particularly about 0.04% to about 0.06% by weight. In yet further embodiments, the pH adjuster is citric acid.

In some embodiments, the antiviral lubricating composition may further comprise one or more optional preservatives that may be added to prevent microbial growth in the antiviral lubricating composition during storage. Any of the one or more preservatives may be selected from preservatives known to those skilled in the art, including, but not limited to, one or more of methylparaben, benzoic acid, salicylic acid, sorbic acid, propylparaben, and sodium dehydroacetate, and combinations thereof. The preservative may be present in the composition of the present invention in an amount up to about 1% by weight of the composition.

In some embodiments, the antiviral lubricating composition can optionally further comprise one or more sweeteners that enhance the flavor of the composition when in contact with the human mouth. In some embodiments, the sweetener is an artificial sweetener, the presence of which can also inhibit bacterial growth in the antiviral lubricating composition during storage. Non-limiting examples of artificial sweeteners can include, but are not limited to, aspartame, saccharin, sucralose, neotame, and acesulfame potassium. In a further embodiment, the sweetener is saccharin. In yet a further embodiment, the antiviral lubricating composition further comprises up to about 0.005% by weight of saccharin. In yet a further embodiment, the antiviral lubricating composition comprises about 0.125% by weight of saccharin.

In addition to or instead of sweeteners, the antiviral lubricating compositions may contain other aromatics that can mask either the aroma of the composition itself or the aroma of the skin or epithelial tissue to which the antiviral lubricating composition is applied. Optionally, the antiviral lubricating composition may further comprise one or more odor-causing agents or fragrances. Non-limiting examples of such fragrances include vanilla, lavender, oregano, thyme, lemongrass, lemons, oranges, anise, clove, aniseed, cinnamon, geraniums, roses, mint, peppermint, citronella, eucalyptus, sandalwood, cedar, rosemary, pine, vervain, flea grass, or rattan millet, or combinations thereof, although any essential oil-based fragrance may be selected. In other embodiments, the antiviral lubricating composition may further comprise one or more chemical, odor-causing compounds that are responsible for the odor or fragrance contained in an essential oil-based fragrance. Non-limiting examples of chemical aroma generating compounds that may be present in any of the antiviral lubricating compositions include carvacrol, eugenol, linalool, thymol, p-cymene, myrcene, borneol, camphor, caryophylline, cinnamaldehyde, geraniol, nerol, citronellol, and menthol, and combinations thereof.

In some embodiments, the antiviral lubricating composition can optionally further comprise one or more metal salts. The addition of metal salts can provide several benefits, including controlling the ionic strength of the composition, enhancing its antibacterial or antiviral activity, or adding to the solubilization of one or more components. The metal salts that can be added can include, but are not limited to, zinc, silver, copper, alkali metal salts, or alkaline earth metal salts. In further embodiments, the metal salt is a zinc salt or a sodium salt.

In some embodiments, the antiviral lubricant composition can optionally further comprise one or more pharmaceutical antiviral, antifungal, or antibacterial compounds.

The present invention also provides several methods for reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between two or more partners engaged in sexual activity, using the antiviral lubricating composition produced by the method described below. In a first embodiment, the method comprises contacting the antiviral lubricating composition with skin or epithelial tissue of one or more partners, the skin or epithelial tissue being located on or within at least one of the vagina, anus, mouth, or penis. As used herein, the term "vagina" includes the vagina itself and/or the skin or epithelial tissue surrounding the vagina, including but not limited to the vulva, labia, clitoris, vaginal opening, and cervix. In a further embodiment, at least one partner is male and at least one partner is female. In another further embodiment, at least two partners are male. In yet another embodiment, at least two partners are female.

In another embodiment, the antiviral lubricating composition can be contacted with the skin of one or more sexual partners, particularly the skin located on or in at least one of the vagina, anus, mouth, or penis, prior to sexual intercourse to prophylactically inhibit the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, from one sexual partner to another. In such an embodiment, the antiviral lubricating composition can be contacted with the skin of one or more sexual partners less than about 8 hours, less than 4 hours, less than 2 hours, less than 1 hour, less than 30 minutes, less than 15 minutes, less than 5 minutes, less than 1 minute, or less than about 30 seconds prior to sexual intercourse, and up to less than about 1 second prior to sexual intercourse. In other embodiments, the antiviral lubricating composition can be contacted with the skin of one or more sexual partners at least about 30 seconds, 1 minute, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, or about 8 hours prior to sexual intercourse.

In another embodiment, the antiviral lubricating composition can be contacted with the skin of one or more sexual partners, particularly the skin located on or in at least one of the vagina, anus, mouth, or penis, after sexual intercourse to reduce the cell-to-cell spread of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, after HPV is transmitted by skin-to-skin contact. In such an embodiment, the antiviral lubricating composition can be contacted with the skin of one or more sexual partners less than about 8 hours, less than 4 hours, less than 2 hours, less than 1 hour, less than 30 minutes, less than 15 minutes, less than 5 minutes, less than 1 minute, or less than about 30 seconds, less than about 1 second, after sexual intercourse. In other embodiments, the antiviral lubricating composition can be contacted with the skin of one or more sexual partners at least about 30 seconds, 1 minute, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, or about 8 hours after sexual intercourse.

In another embodiment, a method for reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between two or more partners engaged in sexual activity further comprises the steps of: providing a substrate having one or more skin-contacting surfaces, the substrate being configured to be inserted into one or more body cavities selected from the group consisting of the vagina, mouth, or anus; lubricating one or more skin-contacting surfaces of the substrate with an antiviral lubricating composition, thereby producing a lubricated substrate; contacting the lubricated substrate with skin or epithelial tissue located on or within at least one of the vagina, anus, mouth, or penis of one or more partners; and transferring the antiviral lubricating composition from the lubricated substrate to the skin or epithelial tissue. In some further embodiments, only one of the partners, either male or female, uses the substrate during sexual activity. In other further embodiments, there are two or more partners using the substrate, and any of the sexual partners may be either male or female.

Substrates suitable for use in conjunction with the method of the present invention can include any object, device, or accessory that can be used to contact the inner or outer surface of the vagina, anus, mouth, or penis during sexual activity.Non-limiting examples of substrates that can be used according to the method of the present invention include condoms, having materials including, but not limited to, rubber, latex, plastic, wood, and/or metal; sexual accessories such as sex toys, dildos, vibrators, rings, beads, and internal applicators.Such examples are described in U.S. Patent Nos. 6,983,751 and 9,119,763; U.S. Design Patent No. D599486; and U.S. Patent Publication No. 2006/0178602, the disclosures of which are incorporated by reference in their entirety.Those skilled in the art will understand that there are countless other examples of substrates, commercially available and improvised, whether sexually themed or not, that can be used during sexual activity and to which the antiviral lubricating composition of the present invention can be applied.

In another embodiment, the substrate is a condom. As used herein, the term "condom" includes devices designed to be worn in or on the penis, vagina, anus, or finger by a man or woman. Condoms can also be worn over sexual accessories, as described below. The antiviral lubricating composition can be applied to the skin-contacting surface located on at least one of the inner surface of the condom or the outer surface of the condom before or after placing the condom on or in the penis, finger, vagina, anus, mouth, or other body part or object. In a further embodiment, a condom pre-lubricated with any of the antiviral lubricating compounds of the present invention can be provided in a package that encloses the lubricated condom and seals it from the external environment outside the package. In yet a further embodiment, the package includes a water-tight seal, thereby preventing loss of the antiviral lubricating composition, before opening the package and applying the pre-lubricated condom over the penis or similar sexual accessory device and engaging in sexual activity. Methods for lubricating condoms and packaging them to protect them from the external environment before use during sexual activity are well known in the art.

In some embodiments where a condom is the substrate, the method of reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexually engaged partners further comprises the steps of lubricating the skin-contacting surface of the condom; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more partners with the lubricated skin-contacting surface of the condom; and transferring an anti-viral lubricating composition from the lubricated skin-contacting surface of the condom to the skin or epithelial tissue.

In further embodiments where the substrate is a condom, the method of reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between two or more partners engaged in sexual activity further comprises the steps of placing the condom on the finger or penis of one partner; lubricating the exterior surface of the condom with an antiviral lubricating composition; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners with the lubricated exterior surface of the condom; and transferring the antiviral lubricating composition from the lubricated exterior surface of the condom to the skin or epithelial tissue.

In other further embodiments where the substrate is a condom, the method of reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between two or more partners engaged in sexual activity further comprises the steps of lubricating the condom; sealing the lubricated condom in a package; storing the lubricated condom in the package; removing the lubricated condom from the package; applying the lubricated condom to the finger or penis of one sexual partner; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners with the lubricated condom; and transferring an antiviral lubricating composition from the lubricated condom to the skin or epithelial tissue.

In another embodiment, the substrate is an internal applicator.Internal applicators suitable for use in conjunction with the method of the present invention can be configured to be inserted into a human body cavity and can include any object, device, or accessory that can transfer the antiviral lubricating composition to epithelial tissue in a human body cavity.Non-limiting examples of internal applicators that can be used according to the method of the present invention include syringes, pipettes, swabs, cannulas, elongated sticks or rods, and wearable inserts, having materials that can include, but are not limited to, rubber, latex, plastic, wood, and/or metal. Examples of such are described in U.S. Patent Nos. 2,546,754, 4,557,720, 4,808,166, 6,503,220, 6,537,260, 7,442,179, 7,591,808, 9,290,551, 9,757,549, and 9,884,173, the disclosures of which are incorporated by reference in their entireties. Those skilled in the art will appreciate that there are numerous other examples of commercially available and ready-to-use internal applicators that can be applied with the antiviral lubricating composition of the present invention and contacted with the skin or inserted into a body cavity to transfer the antiviral lubricating composition to epithelial tissue within the body cavity.

In another embodiment, the internal applicator comprises a skin-contacting surface configured to contact epithelial tissue within a human body cavity, particularly within the vagina or rectum. In another embodiment, the internal applicator has a container configured to house or contain the antiviral lubricating composition prior to transferring the antiviral lubricating composition to epithelial tissue within a human body cavity. In either case, the internal applicator can be provided in a package with or without the antiviral lubricating composition. In a further embodiment, the internal applicator is pre-lubricated with the antiviral lubricating composition and sealed within the package to protect the lubricated internal applicator from the external environment and prevent loss of the antiviral lubricating composition prior to transferring to epithelial tissue within a human body cavity. Methods for applying lubricants or therapeutic substances to internal applicators and packaging them are well known in the art.

In another aspect, the present invention also provides a method for reducing, inhibiting, or ameliorating the transmission, symptoms, or effects of non-sexually associated viruses. The method includes the steps of (a) providing any of the antiviral lubricating compositions described above, and (b) contacting skin or epithelial tissue, either inside or outside the body, where viral infection is known or suspected to be present. The antiviral lubricating composition can be applied to the skin or epithelial tissue using a finger or any of the applicators described above. In another aspect, a lubricated swab, stick, or rod can be inserted into any of the body cavities described above, including the mouth and nose, and contacted with epithelial tissue inside the nasal cavity or throat.

Non-limiting examples of virus taxonomic families that can be treated with any of the antiviral lubricating compositions of the present invention include Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, Coronaviridae, Retroviridae, Herpesviridae, Padromaviridae, Picornaviridae, Reoviridae, and Adenoviridae, and combinations thereof. Such viruses within these taxonomic families can include, but are not limited to, Severe Acute Respiratory Disease (SARS) 1 and 2 (COVID-19); Influenza A, B, and C; Enterovirus, Rhinovirus, Poliovirus, Adenovirus, Rotavirus, and viruses that cause measles, mumps, and chickenpox. In another embodiment, the antiviral lubricating composition can be applied to the skin or epithelium of a human having a viral infection or as a prophylaxis to prevent the animal from receiving a viral infection. In another embodiment, the antiviral lubricating composition can be applied to the skin or epithelium of an animal having a viral infection or as a prophylaxis to prevent the animal from receiving a viral infection.

Processing of the Antiviral Lubricant Composition The antiviral lubricant composition produced by the methods of the present invention is unique in that it has the ability to inhibit viral activity, including the viral activity of sexually transmitted viruses such as HPV, HIV, and HSV, and has optimized viscosity, lubricity, and feel that enhances its performance as a lubricant during sexual activity, while at the same time minimizing the osmolality of the composition. In certain embodiments of the invention, a method of forming an antiviral lubricating composition of the invention can include the steps of: (a) providing a carrageenan powder having carrageenan, the carrageenan having at least about 90% by weight lambda-carrageenan and up to about 10% by weight iota-carrageenan; (b) combining the carrageenan powder with an aqueous solution having a polyol while mixing to form a cloudy carrageenan suspension; and (c) heating the cloudy carrageenan suspension to a temperature of at least 60° C. and mixing for a time sufficient to convert the cloudy carrageenan suspension to a clarified homogenous solution, thereby forming an antiviral lubricating composition; wherein (i) the antiviral lubricating composition has from about 0.5% by weight to about 2.3% by weight carrageenan and up to about 10% by weight polyol; (ii) the antiviral lubricating composition has a viscosity of less than about 5,000 cP; (iii) the antiviral lubricating composition is translucent; and (iv) the antiviral lubricating composition has a turbidity of less than 25 nephelometric turbidity units (NTU).

In another embodiment, the method of forming the antiviral lubricant composition of the present invention can further include a premixing step of first combining carrageenan powder and polyol to form a wet carrageenan mixture having carrageenan and polyol. Without being bound to a particular theory, it is believed that premixing and dispersing the carrageenan powder in the polyol before adding water partially disentangles the carrageenan polysaccharides and makes additional polarizable contacts available to interact upon addition of the aqueous solution. Premixing is believed to have several advantages, including, but not limited to, mixing under low speed and low shear conditions; heating at low temperatures to homogenize the carrageenan in the aqueous solution; facilitating the efficiency of each mixing step, especially the mixing to homogenize the carrageenan in the aqueous solution; and protecting the carrageenan polysaccharides from breaking down into smaller segments, which can adversely affect the viscosity and performance of the composition as a personal lubricant (see below). In a further embodiment, a method of forming the antiviral lubricating composition of the present invention includes the steps of: (a) providing a carrageenan powder having carrageenan, the carrageenan having about 90% by weight lambda-carrageenan and up to about 10% by weight iota-carrageenan; (b) mixing the carrageenan powder with a polyol to form a wet carrageenan mixture, the weight ratio of glycol to carrageenan being about 1:1 to about 10:1; (c) combining the wet carrageenan mixture with an aqueous solution while mixing to form a cloudy carrageenan suspension, the mixture of the aqueous solution and the carrageenan being about 1:1 to about 10:1; (d) heating the cloudy carrageenan suspension to a temperature of at least 60° C. and mixing for a time sufficient to convert the cloudy carrageenan suspension to a clear homogenous solution, thereby forming an antiviral lubricating composition, wherein (i) the antiviral lubricating composition has from about 0.5% to about 2.3% by weight of carrageenan and up to about 10% by weight of polyol, (ii) the antiviral lubricating composition has a viscosity of less than about 5,000 cP; (iii) the antiviral lubricating composition is translucent; and (iv) the antiviral lubricating composition has a turbidity of less than 25 NTU.

In particular, the viscosity of an antiviral lubricant composition is a key factor in its performance as a personal lubricant that can be used in conjunction with sexual activity.Ideally, a personal lubricant has sufficient viscosity to be applied to the skin or epithelial tissue and remain there until sexual activity begins, while also having a rheological profile that allows lubrication and moisture from the composition to be maintained throughout the entire duration of sexual activity.The presence of carrageenan in the composition is the opposite of sexual lubricant performance, as the viscosity of the composition increases exponentially as a function of carrageenan concentration (see Example 3 below).

Similarly, the viscosity of the antiviral lubricant composition is sensitive to the balance of several factors, including, but not limited to, the identity and relative concentrations of the kappa-, iota-, and lambda forms of carrageenan, in addition to the total carrageenan concentration; the concentration and identity of additional components, particularly polyols; and the weight ratio of carrageenan to polyol, if polyol is present. Viscosity also depends on the processing step itself, including, but not limited to, one or more heating of the wet carrageenan mixture, the carrageenan suspension, and/or the antiviral lubricant composition; the addition rate of any components of the composition; the speed and duration of the mixing step; and the type of rotor used for mixing. In short, all of the above factors must be adjusted to optimize the performance of the antiviral lubricant composition during sexual activity.

In another embodiment, the viscosity of the antiviral lubricating composition depends not only on the total carrageenan concentration, but also on the relative concentrations of the kappa, iota, and lambda forms of carrageenan, which have different effects on the exponential rate of increase in the viscosity of the antiviral lubricating composition. As an example, the presence and increasing concentration of kappa-carrageenan causes a rapid increase in the viscosity of the composition, but the exponential rate of growth caused by the presence and increasing concentration of iota-carrageenan is less than that of kappa-carrageenan. The exponential rate of growth caused by the presence and increasing concentration of lambda-carrageenan is less than both kappa-carrageenan and iota-carrageenan. Thus, a composition that is primarily lambda-carrageenan has a lower viscosity than a composition that is primarily kappa-carrageenan and/or iota-carrageenan. As a result, as described above, the antiviral lubricating composition of the present invention can have about 90% or more lambda-carrageenan and up to about 10% of either or both of kappa-carrageenan or iota-carrageenan. In yet further embodiments, the antiviral lubricating composition has about 90% lambda-carrageenan and about 10% kappa-carrageenan.In other yet further embodiments, the antiviral lubricating composition has about 90% lambda-carrageenan and about 10% lambda-carrageenan.

The physical form in which carrageenan mixtures are obtained also influences how they must be processed. When carrageenans are obtained as raw extracts, they are already primarily liquid. However, the shelf life of raw carrageenan extracts is usually shorter than that of solid powders, and carrageenan extracts may contain undesirable or harmful components. As a result, it is common to obtain dry carrageenan in powder form for use in the food or pharmaceutical industry, but this comes with the trade-off that carrageenan must be resolubilized for use in liquid compositions.

In applications where carrageenan is ultimately used as a thickening agent, carrageenan powder can be easily solubilized by prolonged high shear and high speed mixing conditions, often under aggressive heating conditions. However, carrageenan powder cannot be processed in the same way to produce the antiviral lubricating composition of the present invention, because such conditions cause the resulting composition to lose its lubricity over time, especially when subjected to shear thinning stresses that occur during sexual activity. Without being bound by any particular theory, it is believed that the length of the carrageenan polysaccharides directly correlates with the lubricity and moisture of the resulting composition. As the average length of the polysaccharides increases, the lubricity of the composition also increases. On the other hand, solubilizing carrageenan powder under high shear and high stress conditions causes the resulting composition to dry out prematurely.

In another aspect, the solubilization of carrageenan powder can be aided by adding the powder to a polyol.As mentioned above, polyols are commonly included in personal lubricant compositions due to the pleasurable properties that their presence provides during sexual activity.The multiple hydroxyl groups of each polyol molecule provide additional benefits, as they provide intermolecular contacts that allow individual sugars within the larger carrageenan polysaccharide to interact in solution.Without being limited to another theory, as the amount of polyol mixed with the carrageenan powder to form a wet carrageenan mixture increases, the number of polar functional groups within each carrageenan polysaccharide that are available to interact with and solubilize aqueous solvent also increases, causing a concomitant increase in the viscosity of the antiviral lubricant composition.

Conventional antiviral lubricating compositions containing polyols with lambda-carrageenan lubricant compositions have been synthesized by simply adding carrageenan powder to a bulk solvent containing greater than 37% by weight propylene glycol (see Example 1 below). At this concentration, the propylene glycol concentration causes a dangerous increase in the osmolality of the composition. However, it was found that simply lowering the polyol concentration in the solvent was not enough to completely homogenize the carrageenan powder, even when heated to 75°C. Instead, multiple "hydrosealed" clumps were formed that contained dry carrageenan powder surrounded by hemihydrated carrageenan molecules that were impermeable to the addition of water. The same was true for dry powders that were only exposed to aqueous atmospheric conditions, and a similar phenomenon was observed in the '098 patent (noted above).

In some embodiments, the method of forming the antiviral lubricating composition of the present invention can include first mixing the carrageenan powder with at least one polyol to form a wet carrageenan mixture prior to the addition of the carrageenan. In further embodiments, first solubilizing the carrageenan powder in the polyol facilitates complete homogenization of the carrageenan polysaccharides within the antiviral lubricating composition.

The identity of the polyol and the weight ratio of the polyol to the carrageenan also affect the viscosity of the antiviral lubricating composition. As a non-limiting example, 1,2-propanediol is about 50 times more viscous than water, while glycerol is about 23 times more viscous than 1,2-propanediol. Thus, an antiviral lubricating composition can have a much higher concentration of 1,2-propanediol than a second composition containing glycerol while having the same viscosity. As a result, in another embodiment, the weight ratio of polyol to carrageenan in the wet carrageenan mixture is at least 1:10, at least 1:5, 1:1, 2:1, 4:1, 6:1, 8:1, 10:1, 20:1, 30:1, or 40:1, up to at least 50:1. In a further embodiment, the weight ratio of polyol to carrageenan is about 1:1 to about 10:1. In yet a further embodiment, the polyol is 1,2-propanediol.

Similarly, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension also affects the viscosity of the antiviral lubricating composition. In some embodiments, as the weight ratio of the aqueous solution to the wet carrageenan mixture increases, the viscosity of the antiviral lubricating composition decreases. In further embodiments, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension is about 3:1 to about 60:1. In yet further embodiments, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension is about 8:1 to about 45:1.

In another embodiment, heating one or more of the wet carrageenan mixture, the carrageenan suspension, and/or the antiviral lubricating composition allows the carrageenan to solubilize and homogenize in water. Without being bound to a particular theory, it is believed that heating the carrageenan causes at least partial unfolding of each carrageenan polysaccharide and disruption of the intermolecular interactions between the polysaccharides, both of which increase the viscosity of the composition. As heating continues, the carrageenan polysaccharides begin to solubilize in the aqueous solution, decreasing the viscosity and forming a uniform antiviral lubricating composition. However, if the composition continues to be heated after all the carrageenan has been homogenized, the viscosity of the composition may continue to decrease and the polysaccharides themselves may increasingly dissociate into oligosaccharides with smaller molecular weights and chain lengths. In a further embodiment, the carrageenan suspension is heated until an antiviral lubricating composition is formed with a viscosity of less than about 5,000 cP. In still further embodiments, the carrageenan suspension is heated until an antiviral lubricating composition is formed having a viscosity of about 1,000 cP to about 4,000 cP.

Compositions containing carrageenan, such as non-homogenized carrageenan suspensions, are typically cloudy, hazy, or turbid, with numerous carrageenan particles visible to the naked eye. Without being bound to a particular theory, it is believed that the cloudiness of the carrageenan suspension is due to the formation of aggregates before two or more carrageenan polysaccharides are fully unwound and exposed to an aqueous solvent. In another embodiment, the carrageenan suspension is heated until a translucent antiviral lubricating composition is formed. In a further embodiment, the carrageenan suspension is heated until a transparent antiviral lubricating composition is formed. In such an embodiment, the translucent and/or transparent properties of the antiviral lubricating composition are maintained even after extended packaging and/or storage. In yet a further embodiment, there are substantially zero visible particles, aggregates, or agglomerates in the antiviral lubricating composition. In yet a further embodiment, the substantially homogenous antiviral lubricating composition is a solution.

The turbidity of any of the mixtures, suspensions, or antiviral lubricant compositions disclosed herein can be quantitatively described based on the method of determining the concentration of suspended particles in the sample, including, but not limited to, Formazin Nephelometric Units (FNU), Jackson Turbidity Units (JTU), NTU, optical density, Helm Units, parts per million (PPM), and the like. FNU and NTU are widely used to describe the turbidity of compositions with small particles uniformly distributed, and are measured by measuring the amount of light scattered at 90 degrees to the incident light beam. In particular, NTU is measured using visible light, typically from about 400 nm to about 680 nm, as the incident light beam, while FNU is measured using infrared light, typically from about 780 nm to about 900 nm, as the incident light beam.

In another embodiment, the turbidity of any of the mixtures, suspensions, or antiviral lubricating compositions described herein is characterized as a function of NTU. In yet further embodiments, the turbidity of the carrageenan suspension when the carrageenan is added to an aqueous solution is at least about 100 NTU, including at least about 200 NTU, 300 NTU, 400 NTU, 500 NTU, 600 NTU, 700 NTU, 800 NTU, 900 NTU, 1000 NTU, 2000 NTU, or 3000 NTU, including at least about 4000 NTU. In other yet further embodiments, the turbidity of the homogenized antiviral lubricating composition is less than about 25 NTU, including less than about 20 NTU, less than 15 NTU, less than 10 NTU, less than 8 NTU, less than 6 NTU, less than 5 NTU, less than 4 NTU, less than 3 NTU, or less than 2 NTU, to less than about 1 NTU. In still further embodiments, the turbidity of the homogenized antiviral lubricant composition is about 5 NTU or less.

In another embodiment, the antiviral lubricant composition made by the method of the present invention, particularly an antiviral lubricant composition that may come into contact with the mouth during sexual activity, can be homogenized to have a turbidity that is approximately equivalent to that of drinking water.Governments, health agencies, and other regulatory bodies set forth safety standards to protect humans and animals from potentially dangerous health conditions caused by agents that increase the turbidity of a solution, including, but not limited to, polymers and other macromolecules; insoluble small molecules; and bacteria and other microorganisms.The WHO has determined that drinking water should not exceed 5 NTU, and ideally should be less than 1 NTU.In the United States, systems utilizing conventional or direct filtration methods are required to reduce the turbidity of drinking water to less than 1 NTU, with some areas striving to achieve turbidity levels of less than 0.1 NTU.

In another embodiment, the type of mixing device, rotation speed, and mixing time can be optimized to control the viscosity of the resulting antiviral lubricating composition and to disperse and homogenize the carrageenan in the aqueous solution. In some embodiments, mixing can be performed under low shear conditions for a time sufficient to homogenize the composition while maintaining the length of each carrageenan polysaccharide and maintaining their lubricity before applying the composition to skin or epithelial tissue, particularly before or in connection with sexual activity. In contrast, and in other embodiments, mixing can be performed under high shear conditions for a minimum time, but mixing beyond the minimum time can irretrievably destroy the carrageenan polysaccharide, reducing the viscosity of the composition and reducing the performance of the composition as a lubricant during sexual activity. Non-limiting examples of mixers include, but are not limited to, screw mixers, tumble mixers, ribbon mixers, and paddle mixers. In still further embodiments, a paddle mixer can be used for each of the mixing steps to form the antiviral lubricating composition. Similarly, mixing at a relatively low speed maintains the structural integrity of each polysaccharide. In other still further embodiments, each mixing step is performed at a mixing speed of about 500 RPM or less. In yet a further embodiment, mixing of the antiviral lubricant composition after homogenizing the carrageenan in the aqueous solution can be performed at a speed of about 250 RPM or less.

In another embodiment, the method of forming the antiviral lubricant composition can further include several steps including: (e) cooling the homogenized antiviral lubricant composition until the temperature of the antiviral lubricant composition is less than about 30° C.; (f) mixing one or more pH adjusters into the cooled antiviral lubricant composition in an amount sufficient by weight to adjust the antiviral lubricant composition to a pH of about 3.5 to about 7.0; (g) optionally mixing one or more sweeteners into the carrageenan suspension or cooled antiviral lubricant composition at up to 0.5% by weight of the antiviral lubricant composition; (h) optionally mixing one or more preservatives into the carrageenan suspension or cooled antiviral lubricant composition at up to 1% by weight of the antiviral lubricant composition. In further embodiments, each of the pH adjusters, sweeteners, and preservatives described above, as well as additional ingredients such as salts and/or flavorings, can be included in the antiviral lubricant composition to supplement its anti-HPV activity and/or improve performance during sexual activity. The composition properties as a result of the addition of pH adjusters, sweeteners, and preservatives are described above.

In another embodiment, the above method can be used to homogenize carrageenan mixtures with different lambda, kappa, and iota-carrageenan ratios in aqueous solvents at any desired viscosity. In some embodiments, lambda-carrageenan comprises at least about 50% by weight of the carrageenan powder, including at least about 60 or 70% by weight, up to about 80% by weight of the carrageenan powder. In other embodiments, lambda-carrageenan comprises less than about 85% by weight, less than 80% by weight, or less than 70% by weight to less than about 60% by weight of the carrageenan powder. In such embodiments, the amount of kappa-carrageenan and iota-carrageenan, if present, can be increased so that kappa-carrageenan and iota-carrageenan together comprise up to about 50% by weight of the carrageenan powder, for example up to 40% by weight, up to 30% by weight, up to 20% by weight.

Although specific embodiments of the present invention have been described, the present invention can be further modified within the spirit and scope of the disclosure. Those skilled in the art will recognize or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents are therefore deemed to be within the scope of the present invention, and the present application is therefore intended to cover any variations, uses, or adaptations of the invention using its general principles. The present invention is also intended to cover departures from the disclosure as come within known or customary practice in the art to which the invention pertains and which fall within the scope of the appended claims.

It will be understood that certain features of the invention that are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, for brevity, various features of the invention that are described in the context of a single embodiment may also be provided separately or in any suitable subcombination or with any other described embodiment of the invention, as appropriate. Certain features described in the context of various embodiments are not to be regarded as essential features of those embodiments, unless the embodiment cannot function without those elements.

The contents of all references, patents, and patent applications mentioned in this specification are incorporated herein by reference and should not be construed as an admission that such references are available as prior art to the present invention. All publications and patent applications incorporated herein are indicative of the level of skill of those skilled in the art to which this invention pertains, and are incorporated to the same extent as if each individual publication or patent application was specifically and individually indicated by reference.

The present invention is further illustrated by the following examples and prophetic examples, none of which should be construed as limiting the present invention. Moreover, to the extent that section headings are used, they should not be construed as necessarily limiting. The use of the past tense to describe examples shown to be constructive or prophetic is not intended to reflect that the constructive or prophetic examples were actually performed.

The following examples and prophetic examples illustrate the presently most well known aspects of the invention. However, it should be understood that the following are merely exemplary or illustrative of the application of the principles of the invention. Numerous modifications and alternative compositions, methods, and systems may be devised by those skilled in the art without departing from the spirit and scope of the invention. Thus, although the invention has been described in detail, the following examples provide further details regarding what are presently believed to be the most practical and preferred aspects of the invention.

EXAMPLES Example 1 Preparation of a High Osmolality Personal Lubricant Composition The following antiviral lubricant composition was prepared according to the procedure used in the commercial preparation of Divine 9®, a lambda-carrageenan based personal lubricant.

<u style="Single">component</u>55.70% (w/w) deionized water 37.40% (w/w) propylene glycol 5.00% (w/w) 2.5% (w/v) sodium saccharin in deionized water 1.40% (w/w) Viscarin® PC209 carrageenan powder 0.04% (w/w) citric acid 0.01% (w/w) sodium hydroxide 0.95% (w/w) GeoGard ECT preservative (Lonza Consumer Care) 0.03% (w/w) GeoGard 111 - sodium dehydroacetate preservative (Lonza Consumer Care)

All ingredients except Viscarin® PC209 carrageenan powder were combined and mixed together thoroughly. With constant mixing, the composition was gradually heated to 75°C. When the composition reached 50°C, Viscarin® PC209 carrageenan powder was gradually mixed in until all of the carrageenan powder had been added. Mixing of the composition was continued at 75°C for approximately 2 hours until all of the Viscarin® PC209 carrageenan powder was dissolved. Once the carrageenan powder was dissolved, mixing was stopped and the composition was rapidly cooled. Once the temperature of the composition reached 30°C, citric acid was added to bring the pH to approximately 6.5±0.25.

Example 2: Preparation of a low osmolality antiviral lubricant composition The following antiviral lubricant composition was prepared according to an embodiment of the present invention and the following procedure.

<u style="Single">component</u>88.49% (w/w) deionized water 4.40% (w/w) 1,2-propanediol 5% (w/w) 2.5% (w/v) sodium saccharin in deionized water 1.60% (w/w) Viscarin® PC 209 carrageenan powder 0.05% (w/w) citric acid 0.32% (w/w) 2-phenoxyethanol 0.11% (w/w) chlorphenesin 0.03% (w/w) GeoGard 111-sodium dehydroacetate preservative (Lonza Consumer Care)

Viscarin® PC 209 carrageenan powder and 1,2-propanediol were mixed for approximately 10 minutes to form a wet carrageenan mixture using a Mixer Direct R-AD665 industrial gallon paddle mixer equipped with two folding impeller blades operating at 500 RPM. After 10 minutes, no agglomerated particles of powder were observed in the wet carrageenan mixture. With continued mixing, approximately 90% by volume of water and total saccharin were added to the wet carrageenan mixture over an additional 5 minutes to form a cloudy carrageenan suspension. The carrageenan suspension was heated to 70°C and mixed under the same mixing conditions until the carrageenan powder was completely homogenized in the water. After approximately 90 minutes, homogenization was achieved upon transition from a cloudy suspension to a clear solution. After homogenization, mixing was continued for an additional 10 minutes. The mixer was paused and the composition was cooled to below 30°C. Once cooled, the preservative, citric acid, and remaining water were added to the composition and mixed at 250 RPM for 20 minutes. The resulting antiviral lubricating composition was translucent and had a pH of about 6.5±0.25.

Example 3: Exponential Effect of Carrageenan Concentration on Composition Viscosity To evaluate the effect of carrageenan on the viscosity of antiviral lubricating compositions, several compositions were formulated with various carrageenan concentrations. The first sample, Sample VI, was prepared according to the same ingredient specifications and procedures as the composition of Example 1. Additional antiviral lubricating compositions (Samples V2-V5) containing different concentrations of carrageenan were prepared using the procedure of Example 2. The amount of water added was adjusted as necessary. The final volume of each sample composition was 200 mL. The concentration of carrageenan and the viscosity of each sample are shown in Table 2 below.

<tables><img file="JP7635277B2_D0003.tif" /></tables>

Each of the viscosity measurements was performed using a Brookfield LVF Dial Reading Viscometer using a #2 spindle at 12 revolutions per minute, following the instructions provided with the instrument. The relationship of viscosity of the antiviral lubricant composition as a function of carrageenan concentration is shown in Figure 1. The data was fit to an exponential model using Microsoft Excel to obtain the R²A fitted curve with a value of 0.994 is obtained, indicating a strong correlation between the data and the model.

Example 4: Linear Effect of 1,2-Propanediol on Composition Osmolality To evaluate the effect of 1,2-propanediol on the osmolality of the antiviral lubricating compositions, several compositions were formulated with varying concentrations of 1,2-propanediol. The first sample, Sample O1, was prepared according to the same ingredient specifications and procedures as the composition of Example 1. Additional antiviral lubricating compositions (Samples O2-O5) with different concentrations of 1,2-propanediol were prepared using the procedure of Example 2. The amount of water added was adjusted as needed. Final volume of each sample composition: 50 mL. The concentration of 1,2-propanediol and the osmolality of each sample are shown in Table 3 below.

<tables><img file="JP7635277B2_D0004.tif" /></tables>

Each of the osmolality measurements was performed with an osmometer capable of measuring freezing point depression according to the United States Pharmacopeial Convention standard protocol (USP&lt;785&gt;, see Osmolarity and Osmolarity, 2017). The relationship of osmolality of the antiviral lubricant composition as a function of 1,2-propanediol concentration is shown in Figure 2. The data was fitted to a linear model using Microsoft Excel, resulting in a linear regression of the R²A fitted line with a value of 0.9974 is obtained, indicating a strong correlation between the data and the model.

Prophetic Example Example 5: Characterization of the Disaccharide Content of Antiviral Lubricating Compositions Each primary form of carrageenan has a different repeating disaccharide structure-iota-carrageenan has alternating disaccharides of D-galactose-4-sulfate and 2-sulfo-3,6-anhydro-D-galactose; kappa-carrageenan has alternating disaccharides of D-galactose-4-sulfate and 3,6-anhydro-D-galactose; lambda-carrageenan has alternating disaccharides of D-galactose-2-sulfate (1-3 linkage) and D-galactose-2,6-disulfate (1,4 linkage). As a result, lambda-carrageenan usually contains more sulfate groups per polymer and is substantially free of the anhydrogalactose residues commonly found in iota-carrageenan and kappa-carrageenan. Thus, the relative ratios of lambda-, iota-, and kappa-carrageenans in the antiviral lubricating composition can be determined by infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy (de Araujo, CA, et al., (2013) Carbohydrate Polymers 91:483-491), and liquid chromatography coupled with mass spectrometry (LC-MS) (see Diez, F., et al., (2017) Development of an Analytical Method to Determine the amount of e Carrageenan in HPMC Capsules by LCMS, American Association of Pharmaceutical Scientists Poster Submission, available online at http://abstracts.aaps.org/Verify/AAPS2017/PosterSubmissions/M8109.pdf on May 3, 2018).

In particular, the IR spectrum of the antiviral lubricating composition can be used to determine both the profile of the composition, which can be compared to other lambda-carrageenan-containing compositions, as well as the relative molar ratios of lambda-, iota-, and kappa-carrageenan types within the composition (see Volery, P., et al., (2004) J. Agric. Food Chem. 52 (25):7457-7463). A typical IR spectral fingerprint region (approximately 800 cm^-1~ approx. 1250cm^-1), carrageenan has several strong and broad absorption bands for residues or functional groups commonly found in each polymer, and at about 1065 cm^-1~ approx. 1020cm^-1, especially around 1050cm^-1It has a strong absorption maximum at 1050cm^-1The intensity of absorbance of specific bands corresponding to residues or functional groups can be used to measure the relative abundance of a particular form of carrageenan in an IR sample by comparing the intensity of the major absorption bands at 1050 cm and 1050 cm.^-1Their intensities relative to the main absorption bands at 100 nm are shown in Table 4 below.

<tables><img file="JP7635277B2_D0005.tif" /></tables>

A study was conducted in accordance with the principles of the present invention to characterize carrageenan in samples of antiviral lubricating compositions. Samples of the antiviral lubricating compositions were subjected to IR spectroscopy analysis in accordance with the procedures set forth in the Joint Food and Agriculture Organization of the United Nations/World Health Organization Compendium of Food Additive Specifications (see "Carrageenan, Compendium of Food Additive Specifications FAO JEFCA Monographs 16; FAO/WHO Publications; Rome, Italy; pp. 7-12). The antiviral lubricating compositions of the present invention are expected to have a unique and characteristic IR spectrum that can be compared to other compositions containing lambda-carrageenan. The IR spectrum of the antiviral lubricating composition is characterized by a peak at 810 cm^-1~820cm^-1And 825cm^-1~830cm^-1It is expected that the antiviral lubricating composition will have a peak at 1000 nm, indicating the presence of lambda-carrageenan in the antiviral lubricating composition. It is also expected that the molar ratio of lambda-carrageenan in the antiviral lubricating composition will be greater than the molar ratios of kappa-carrageenan and iota-carrageenan.

Example 6: Antiviral Efficacy of Antiviral Lubricant Composition Against Respiratory Viruses in Human Subjects A study is conducted in accordance with the principles of the present invention to measure the efficacy of an antiviral lubricant composition in human subjects who have an active viral respiratory infection, such as COVID-19, or who are in close contact with someone who has an active viral respiratory infection. Participants are asked to apply the antiviral lubricant composition of Example 2 to the tip of a swab and insert the swab through their nose until it contacts the epithelial tissue within the nose and nasal cavity. Alternatively, participants are asked to dispense a quantity of the antiviral lubricant composition into their mouth and sip, swirl, or gargle the composition in their mouth before swallowing. The volume of the composition administered by either method is between 0.1 mL and 5 mL. The antiviral lubricant composition of Example 2 can be administered in neat form or diluted prior to administration. Participants are asked to administer the antiviral lubricant composition to their nasal cavity 1-4 times per day. Participants may also be asked to administer the composition before and/or after coming into close contact with another person or going out in public. In the case of active infection, the progression of symptoms is expected to be slowed or reduced in a dose-dependent manner until it is completely eliminated, and the viral load of the virus that is transmitted to subjects who are not sick but are in close contact with sick patients is expected to be delayed, reduced, or eliminated.