Pharmaceutical composition for the prevention of sexually transmissible diseases.

The present invention relates to the prevention of sexually transmitted diseases such as, in particular, AIDS and hereinafter referred to by their common abbreviation "MST".

The most common STDs are caused in particular by viruses, bacteria, parasitic organisms and fungi. With the development of these diseases, n'existe to date no means of prevention of sufficient effectiveness and able to offer an alternative to the use of condoms which we know, however, imperfections and disadvantages.

Indeed, it is known that various chemical agents possess a certain effectiveness of STD organisms. Among the most commonly used agents, mention may be made of diméthylalkylbenzalkonium chloride or benzalkonium chloride and nonoxynol-9 or nonylphenolpolyoxyethylene.

However, these products have only relative effectiveness in that, firstly, their spectrum of action is narrow since it only covers some of the germs that cause STDs and, secondly, the deadline necessary for their action is long and therefore unacceptable when s'agit of STD prevention.

such that contamination is known by the AIDS virus can occur from the very first minutes of its contact with healthy mucous membranes. By contrast, inactivation of the virus by benzalkonium chloride at a concentration of 1% only after a contact time of at least ten minutes, leaving a possibility of extremely important contamination and therefore unacceptable in convenient.

Therefore, the use of known products does not allow effective prevention of STDs, even when they possess virucidal properties.

It is known, moreover, according to EP-A-0113998, that derivatives of cholic acid and deoxycholic acid primarily dehydrocholic, can be used in the treatment of viral infections caused by the virus Herpes Simplex I or II.

However, there is an Action s'agit therapeutic, not preventative while about the present invention is precisely to provide a means of prevention. The line between therapy and prevention n'est not always clear, but understanding the difference between these two modes of action is essential here because ç'est the choice of one or the other which conditions determining pharmaceutical composition used, the implementation of the treatment, its form, its mode of administration and the extent of its use. Unlike preventive action regarding healthy subjects, therapeutic action, such as that proposed in EP-A-0113998, has effect on a subject already reached. In this case, ç'est when the infection is visible, or at least detectable, and therefore established that the patient may use a cure. It is therefore possible to determine very precisely the places infected with Herpes Simplex I or II, where the treatment will be applied, if the topical route is used.

In fact, two administration modes are possible: the way parenteral or topical way in the sense of an application located on the very location specific location infection.

In the present invention, a topical administration through means applying a pharmaceutical composition not on a zone strictly delimited by an infection but instead declared a large area, often complex and always imprecise since the infection that is to be prevented is therefore not shown.

Thus, the term "through topical" as used in the case of therapy and therefore in EP-A-0,113,998 (treatment of a specific item already reached) should not be confused with the same expression used here in the case of prevention, the meaning indicated above, is quite different.

Moreover, in the objetive prevention of STDs, the topical route is preferred to parenteral administration because of the presence of certain compounds necessary for effectiveness but which should not be introduced into the organism. They may, indeed, become toxic when taken at dosages important then metabolized by the body.

Note, finally, that in EP-A-0113998, only the action on virus Herpes Simplex I and II has been described, whereas the present invention relates to prevention against a spectrum extended STD viruses responsible whose main strains are, for example: - The viruses of the Herpes I and II, - The AIDS virus HIV I and HIV II - Virus hépathite B, - The papillomasvirus (HPV).

To this end, the present invention involves the protection of large complex areas.

However, the teaching of EP-A-0113998, does not encourage the skilled person to use a derivative of cholic acid: - Firstly, for effective preventive action during several hours which requires the application of a pharmaceutical composition in a uniform and sufficient manner, on an ill-defined area to be safe but potentially contaminated, is reached and therefore likely contaminate a partner, - secondly, to a spread spectrum virus matching events different from those of Herpes Simplex and therefore much broader scope.

Thus, the present invention provides a pharmaceutical composition containing one or more active ingredients effective in preventing STDs.

The present invention also relates to a pharmaceutical composition for the protection, topically, high risk areas such as the vagina of the woman.

The vagina is a mucous membrane that inherently favors the passage of substances both by emission to the outside of itself by absorption into the body internally.

Or, for effective prevention of STDs, the active principles should not be absorbed by the body, particularly through vaginal mucosa.

Indeed, so far we could not use certain substances for such prevention, although effective, since these substances diffused quickly in the body.

It is this problem solved by the invention.

To this end, the invention provides a pharmaceutical composition for the prevention of sexually transmitted diseases, to be placed in contact with a mucous membrane characterized in that it comprises firstly at least one active ingredient against viruses or bacteria that cause STDs and said the other inhibitor product penetration of said active ingredient through the mucous membrane in combination with a pharmaceutically acceptable carrier suitable for topical administration of the composition.

The invention will be better understood from the detailed description below given by way of indication and is not restrictive.

The penetration inhibitor is an agent inert and non-toxic capable of forming a insulating film and protective to the mucous membranes or skin.

Moreover, to be sufficient, the protection should be effective from the vaginal opening and cover the whole of the mucosa, which is very difficult to achieve due to the extremely numerous folds of the latter.

The pharmaceutical composition of the invention advantageously contains an inert and nontoxic agent dispersing the active principles in order to obtain a uniform and sufficient spreading of the composition.

Preferably, the inhibiting agent of penetration and the dispersing agent contained in the composition according to the invention are constituted by the same compound, especially of the silicone family.

The pharmaceutical composition according to the present invention contains for example a salt of cholic acid as active principle.

It is known that cholic acid is a natural component of bile and is currently used in therapy, as well as pharmaceutically acceptable salts, as choleretic agent.

Known according to patent application EP-A-0285285, the use of a dispersant presented in this document as "any agent capable of lowering the interfacial tension in aqueous medium", in combination with a derivative of cholic acid for the treatment of viral infections. Knowing that the virus uses the proteins of the cell that parasite to form a shell around the nucleic acid chain (DNA or RNA), anti-viral action of the dispersant, postulated in the patent application EP-A 0,285,285 lies in breaking the shell of the virus, unable to invade other cells, is thus destroyed.

It is important to note here that the dispersant, whose action is indicated above, enters into a pharmaceutical composition administered by parenteral route. The pharmaceutical composition containing said dispersant is injected directly into the bloodstream.

The action of the dispersing agent in combination with one or more active ingredients in the pharmaceutical composition according to the present invention is quite different.

Indeed, here, this agent n'intervient not directly on the virus, in contrast to what is described in the patent application above.

The composition according to the invention is intended for administration topically in contrast to modes of administration (parenteral and oral) described in the application EP-A-0 285 285 patent.

The main quality of the film forming agent contained in the composition according to the invention is formed on the entire surface of the area to be protected, a uniform film and insulation which acts as a barrier: - It inhibits the penetration of the active principle in the body, avoiding it from being metabolized; after spreading, it leaves time to act on said active ingredient; - It prevents the spread of viruses responsible for STD through the mucosa. Unwanted viruses are thus maintained in contact with the active ingredient that may destroy them; - Its insulating and protective role is twofold in the sense that on the one hand, it protects a healthy woman against a possible infection by an affected partner and that on the other hand, if a woman has, it protects the partner , by the same insulating effect.

The combination of the film-forming effect and the dispersing effect allows spreading on the entire surface of the folds constituting a vaginal mucosa.

The salt of cholic used in the pharmaceutical composition according to the invention is preferably sodium cholate.

Sodium cholate is a powerful bactericidal and virucidal agent This compound is a substance biological devoid of toxicity and active even at low concentrations. The amount of sodium cholate to implement in the pharmaceutical composition according to the invention is advantageously between 0.2 and 1.5%, preferably between 0.25 and 1% by weight based on the weight of the total composition .

The film-forming agent and dispersing agent preferred for the purposes of the invention is dimethylpolysiloxane which has also an anti-adhesive effect reinforcing the insulating effect of the film.

The amount of dimethylpolysiloxane contained in the pharmaceutical composition object of the present invention is of the order of 10% by weight relative to the total weight of the composition.

Note that according to the invention compared with the amounts of active ingredient, the amount of film-forming agent is very important.

This is due to the fact that we search the formation of a film not only on the whole extent of the surface to be protected (that is large in the case of the vaginal mucosa) but also by a sufficient compactness to obtain an effect insulating barrier as effective as possible and this for two purposes: - Underestimate, (but we want them fully prevent) the risks of transfer of pathogenic agents as well from that direction of the mucosa, - Avoid absorption by the mucous membrane of the active ingredients associated with the film and thus maintain on site said active ingredients where their topical action is necessary.

This amount can be preferably increased rather than diminished since the film-forming effect tends to increase with concentration.

The pharmaceutically acceptable vehicle suitable for the purposes of the invention is a conventional vehicle suitable for topical administration. In the case of the protection of vaginal mucosa, the vehicle must be suitable for internal use and extended.

The skilled preferably choose a vehicle that allows aqueous adhesion and dilution with natural fluids present.

For an advantageous implementation, the composition of the invention may contain, in addition, a buffering agent such as hydrochloric acid in order to adjust the pH to 4.7. This value allows to respect the vaginal flora and Doederlein bacillus. The destruction of non Doederlein bacillus is very important because it has defensive properties capitals against genital infections. It is therefore necessary to preserve it.

The pharmaceutical composition of the invention may be in the form of solutions (vaginal douches), creams or gels.

The skilled person will choose a pharmaceutically acceptable carrier suitable for the chosen format.

The form in which the present composition of the invention is related to its usage. This composition must possess, in addition, a certain viscosity adapted to the manner in which it will be used.

To this end, the pharmaceutical composition of the invention further contains a thickening agent to obtain the proper rheology.

Among the thickening agents conventional, the compound preferred for purposes of the invention is hydroxypropyl methylcellulose, sold under the name commercial "Métholose 60 SH 4000" by the company SEPPIC, 70 Avenue des Champs Elysees, 75008 Paris (France).

This thickener is used to adjust the viscosity to the level best suited to the form of the composition (solution, cream, gel, etc.). The viscosity thus obtained is not modified significantly when the pH of the composition varies during its development.

The importance of this agent will be better understood using the application explained later.

Thus, the most frequently selected dosages for a pharmaceutical composition according to the invention are summarized in Table I: <tables id="tabl0001" num="0001"><table frame="all"><title>Table I</title><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">0.25 to 1% by weight of sodium cholate</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">10% by weight of dimethylpolysiloxane</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">4% by weight of hydroxypropylmethylcellulose</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">hydrochloric acid: amount necessary for pH = 4.7</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">Water: desired amount to 100%.</entry></row></tbody></tgroup></table></tables>

In a more elaborate embodiment of the invention, combining several active ingredients in particular to strengthen the action of sodium cholate, in particular on certain bacteria.

Therefore, the composition of the invention may contain one or more agents virucidal and bactericidal, further having spermicidal properties, in combination with the sodium cholate and the film-forming agent dispersant. Among these virucidal agents, bactericides and spermicides, preferably chosen benzalkonium chloride and / or nonoxynol-9.

We note here that the possibility of using nonoxynol 9 illustrates the advantages provided by the invention. Indeed, the nonoxynol-9 may develop a certain toxicity when it enters the body at high doses, in particular due to its accumulation in the kidneys. In addition, its ability to pass through a vaginal mucosa amounts to about 80%. However, the use of nonoxynol-9 in a composition according to the invention is quite possible and safe thanks to the presence of the insulating film created by the film-forming content in this composition, which is an inhibitor s'opposant, therefore, the penetration of this active ingredient in the body.

The quantities used are preferably comprised between 0.5 and 1% and 0.25 to 1% by weight relative to the total weight of the composition, respectively for benzalkonium chloride and nonoxynol-9.

Thus, a composition which is particularly suitable pharmaceutical purposes of the invention preferably contains the amounts indicated in Table II below: <tables id="tabl0002" num="0002"><table frame="all"><title>Table II</title><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">0.25 to 1% by weight of sodium cholate</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">0.50 to 1% by weight of benzalkonium chloride</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">0.25 to 1% by weight of nonoxynol-9</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">10% by weight of dimethylpolysiloxane</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">4% by weight of hydroxypropylmethylcellulose</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">hydrochloric acid: amount necessary for pH = 4.7</entry></row><row><entry namest="col1" nameend="col1" align="right">-</entry><entry namest="col2" nameend="col2" align="left">Water: desired amount to 100%.</entry></row></tbody></tgroup></table></tables>

The pharmaceutical composition produced according to the proportions of Table II above is especially suitable for STD prevention because of its specificity and provides protection very effective.

Indeed, its action is both virucidal, bactericidal and spermicidal.

It thus makes an effective inactivation of viruses responsible for STD but also bacteria and fungi also responsible STDs, among which are: . Staphylococcus Aureus, . Candida albicans . Streptococcus Agalactiae, . Neisseria gonorrhoeae . Garnella vaginalis, . Trichonomas vaginalis,

The three active agents combined in the composition of Table II act in a complementary way and therefore possess a very wide spectrum of action.

One example is the effective action of nonoxynol-9 on Chlamydia trachomatis which nevertheless causes a very significant increase in infections due to Candida albicans. Now benzalkonium chloride, also present in the composition, possesses it, an action clear on Candida Albicans.

For the prevention of STDs, the pharmaceutical composition of the invention may advantageously be used in combination with a vaginal tampon as described by the inventor in the patent FR-A-2614525. This overcomes the drawbacks inherent buffer to buffer conventional employees in contraception: difficulty of extraction, irritation, lack of discretion. This results from the presence, on the body, at least one recess which serves as a gripping and extraction device.

For an advantageous embodiment of the pharmaceutical composition according to the present invention, the buffer must have, in addition, the characteristics relating to its composition and its method of preparation.

Thus, a buffer used as a carrier of the pharmaceutical composition according to the invention for the prevention of STDs, consists of a foam type with open cells such as, for example a polyurethane foam ether.

Foam of polyurethane ether constituting a buffer used for the purposes of the invention has a density preferably between 15 and 28.

On the other hand, the ether polyurethane foam has a resistance to breakage comprised preferably between 70 to 150 kilo Pascal (KPa).

Finally, the average dimension of the cells contained in the foamed polyurethane ether is preferably between 0.67 and 0.53 millimeters (mm).

For an advantageous implementation of the invention, the buffer is prepared so as to include no "skin" ç'est ie a surface exterior more or less continuous and substantially devoid of open cells.

To do this, the pad is cut from a plate of suitable thickness, itself cut from a block of foam previously stripped of its "skin" outer by a sawing operation.

It belongs to the art of choosing, given the criteria set out above, the shape and dimensions of the buffer adapted to the anatomy of the wearer.

The pharmaceutical composition according to the invention is preferably in the form of an aqueous gel; aqueous due to the body part where the buffer is used. Indeed, it s'agit an internal use in a very sensitive area: the vaginal mucosa, which should not be irritated or damaged. Moreover, this gel form is perfectly adapted to the retention in the buffer. Indeed, the composition should not, for example, go out too abundantly buffer when the pressure exerted on it by the user to insert into the vagina. The buffer front, moreover, be kept and mostly remain effective for a long time, at least several hours, the form of the pharmaceutical composition that permeates the buffer should be such that no excessive excretion this one in the first minutes of its application. The use of a gel is important because it overcomes this drawback that would alter efficiency. This form also allows gel, because of its particular viscosity, good contact with the mucosa and a uniform and sufficient spreading thereon.

The above also highlights the important role of the thickener on the viscosity necessary must have the gel which is impregnated pad.

The amount of aqueous gel according to the invention required to treat a buffer depends on the size and composition thereof. However, experience shows that it is preferable that the buffer is not fully impregnated because firstly, there would be shedding a large amount of gel when the user presses the pad to introduce the vagina, and secondly, we must let the natural fluids the opportunity to be absorbed (substitution) and be neutralized. The amount of gel necessary to impregnate the buffer s'avère meet the above conditions when it is in the order of 25% from the total volume absorption buffer.

Each pad is individually packaged in a sealed capsule.

For a buffer of 45 mm diameter and 20 mm thick, one chooses a capsule having an inner diameter of 46 mm and a height of 24 mm. The game thus be available to the impregnation method of the invention.

The capsule has a flange device 5 mm wide to allow the sealing of the capsule by welding a lid to said flange.

The sealing is facilitated by the presence of small free space remaining above the buffer due to the difference of dimensions of the capsule (24 mm) and buffer (20 mm).

The capsule can be made of a material of the polyvinyl types. The cover, in turn, consists of a conventionally aluminum complex used for the sealing of plastic containers.

According to the invention, the impregnation is carried out as follows:

The required amount of gel is placed in the bottom of the capsule. To buffer 45 X 20 mm, it takes about 5 grams of gel. It then spreads as a thin layer over the entire surface of the capsule.

The pad is then placed on the gel and the capsule is operculated.

The gel enters the capillary buffer.

The impregnation time is about thirty seconds while the sealing is carried out advantageously in seconds, immediately after the filing of the buffer, ç'est to say before the impregnation proper buffer is completed.

Therefore, the impregnation is completed during subsequent packaging operations. In other words, the impregnation is obtained "masked time".

The approach opposite would be to deposit the gel buffer and not in the bottom of the capsule, is not recommended if, as is logical, the volume inside the capsule is close to the volume outside the buffer. In this case, indeed, there is a strong probability that the gel is accidentally driven over the edge of the capsule during its sealing. As the cap must be fixed on this edge, generally by welding, interposing the gel would be an impediment to this welding and that, even more severely than the gel contains a silicone. It would take an insignificant amount of gel to cause imperfect sealing, ç'est ie unsealed.

Furthermore, it n'est not necessary to sterilize the buffer because of its high content of virucidal agents and bactericides.

Thus, the use of a pad impregnated with several active ingredients combined present, due to the complementary activity of these, and new benefits specifically tailored to the prevention of STDs.

In fact, provided with open cells on the entire surface, the buffer allows the aqueous gel which it is impregnated to be present and active upon application of the buffer for insertion into the vaginal orifice and cover bit just the entire vaginal mucosa as and when it progresses, mandatory requirements for protection and instantaneous real.

The gel fraction extracted aqueous buffer during its progression is replaced on the outskirts of the buffer by the gel initially contained in the cells of the central area through communication between the cells open. Moreover, due to this internal transfer, the amount of gel is larger output during intercourse, due to the movements that they assume, which is particularly favorable for the destruction of germs contained in the vaginal environment and in semen and sperm.

Physical spreading of gel therefore has the advantage of being constant and regular, it is not possible with an ordinary buffer. This reinforces the action of dimethyl polysiloxane which, alongside its dispersing properties, forming a protective film on the mucous membranes and skin. An insulating and hydrophobic effect associated with it due to the nature of dimethylpolysiloxane which belongs to the family of silicones.

Since the gel has a low concentration of active ingredients and the film-forming agent has an inhibitory effect penetration of these principles in the body, the gel according to the invention can be repeated use and extended.

Thus, the user can renew the impregnated tampon as often as she wants. The same buffer can be left on for several hours without risk of producing irritation of the mucous vaginal, even if you forget.

Moreover, it is recommended to keep at least six hours after the last sexual intercourse to ensure the best possible protection.

The presence of benzalkonium chloride in the formula in Table II reinforces the action of the existing sodium cholate and avoids the risk of "Toxic Shock Syndrome"

The "Toxic Shock Syndrome" is the result of a proliferation of Staphylococcus Aureus fast when other agents pathogens are destroyed. The severity of this development is the fact that Staphylococcus aureus produces violent toxins that become deadly very quickly. Now benzalkonium chloride, such as sodium cholate, has a marked action on this very dangerous germ.

The pad impregnated as described above provides a double protection. For AIDS, for example, several cases are possible: - Report of sex between a woman and a healthy partner declared disease or HIV: the female organism is isolated and protected by the film covering the vaginal mucosa. The active ingredients destroy infectious agents contained in the sperm or brought by the partner. - Report of sex between a woman declared disease or HIV positive and a healthy partner: the recovery of the vaginal cavity by the film of gel isolates the mucosa and waypoints possible viruses (erosions, burglary). The viruses can not then leave the body feminine reached. The gel ejected from the buffer is also fixed on the penis of the man partner and the film protects the contact directly and ghosting effect on the skin. - Report of sex between a woman and a partner in both declared disease or HIV: frost action avoided serious reinfection with HIV, by mutual isolation and destruction of infectious agents from both sources.

This pad impregnated is therefore particularly suitable for the prevention against AIDS.

The pad impregnated such as that described above can be used for the prevention of STDs, in addition to conventional methods of contraception (pills, IUDs and so on). It can act, including, without risk of moving the son of some IUDs.

It also has the advantage of being discreet. Indeed, unlike the condom, it is not perceived by the couple. This factor, in the case of condoms, very limiting in the development of its use. As regards the present invention, this hindrance is removed.

Furthermore, the pad impregnated is available in a package disposable and tear that can protect it and keep it properly, and it gives and ease of use.

The application described above is a particularly preferred use of the pharmaceutical composition of the invention, including but not limited to fight against the spread of AIDS.

The invention will now be described in more detail using the following examples:

EXAMPLES

Products used:

- Cholate sodium sold by the Company CIPEC, 7 rue Lincoln, 75008 Paris (France). - Benzalkonium chloride sold under the trade name "REWOQUAT B 50" by Schering Corporation, 5 rue Le Corbusier, 94150 Rungis (France). - Nonoxynol 9 sold under the trade name "SIMULSOL 930 NP" by SEPPIC, 70 Avenue des Champs Elysees, 75008 Paris (France). - Polydimethylsiloxane sold under the name commercial "365 MEDICAL GRADE EMULSION" by the Company Dow Corning Corporation, Midland, Michigan 48640 (United States). - Hydroxypropylmethylcellulose sold under the name commercial "METHOLOSE 60 SH 4000" by the company SEPPIC, 70 Avenue des Champs Elysees, 75008 Paris (France).

EXAMPLE I Vaginal tampon impregnated with the aqueous gel according to the formula of Table I

Buffer:

- It is constituted of a polyurethane ether foam having the characteristics as follows: . Density: about 22 . breaking strength: 130 kPa . Average cell size: 0.6 mm. - It measures 45 mm in diameter and 20 mm thick. - It has two recesses, as described in FR-A-2614525.

Gel:

- 5 grams of gel are necessary to impregnate a tampon having the features above. (The total absorption volume of such a buffer is 20 grams.) - The composition of the gel used is the following: <tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">sodium cholate</entry><entry namest="col3" nameend="col3" align="left">0.025 g (0.5%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">Dimethylpolysiloxane (35% solution)</entry><entry namest="col3" nameend="col3" align="left">0.50 g (10%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">hydroxypropyl</entry><entry namest="col3" nameend="col3" align="left">0.20 g (4%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">Hydrochloric acid (1N)</entry><entry namest="col3" nameend="col3" align="left">Qs to pH = 4.7</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">Purified water</entry><entry namest="col3" nameend="col3" align="left">Qs to 5 g</entry></row></tbody></tgroup></table></tables>

Gel preparation:

(This procedure is usable whatever the quantities used) - In a stainless steel tank (Tank B), sodium cholate is dissolved at room temperature in half the amount of purified water. Was added then the dimethylpolysiloxane. This solution is then mixed by stirring until obtaining a homogeneous solution. The products being surfactants, the mixture should be carried out under low stirring speed. - In another vessel in stainless steel double wall (Tank A), half of the amount of purified water was heated to 70 ° C by circulating steam in the double wall. The hydroxypropylmethylcellulose is then introduced and dispersed with stirring until a homogeneous gel. This gel is then cooled to room temperature by circulation of cold water in the double wall of the tank. - The solution obtained in vessel B is added gradually at room temperature, the gel prepared in the vessel A, with agitation, until a homomgène gel. - The pH is adjusted by addition of a 1N hydrochloric acid solution in amount sufficient to achieve a pH of 4.7. - The total mass of the gel is adjusted to 5 grams by addition of purified water in sufficient quantity.

Impregnation of the buffer:

- The gel obtained above is placed at the bottom of a capsule with a diameter inside of 46 mm, a height of 24 mm and a rim peripheral 5 mm wide. - The pad is placed on the gel and it enters the buffer by capillary action. - The capsule is operculated by welding a way to make it watertight lid.

EXAMPLE II Vaginal tampon impregnated with aqueous gel according to the formula in Table II.

Buffer :

- It has the same characteristics as that of Example I.

gel:

- 5 grams of gel are necessary to impregnate the pad. - The composition of the gel used is the following: <tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">sodium cholate</entry><entry namest="col3" nameend="col3" align="left">0.025 g (0.5%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">Benzalkonium chloride</entry><entry namest="col3" nameend="col3" align="left">0.050 g (1%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">nonoxynol-9</entry><entry namest="col3" nameend="col3" align="left">0.025 g (0.5%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">Dimethylpolysiloxane (35% solution)</entry><entry namest="col3" nameend="col3" align="left">0.50 g (10%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">hydroxypropyl</entry><entry namest="col3" nameend="col3" align="left">0.20 g (4%)</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">Hydrochloric acid (1N)</entry><entry namest="col3" nameend="col3" align="left">Qs to pH = 4.7</entry></row><row><entry namest="col1" nameend="col1" align="right">.</entry><entry namest="col2" nameend="col2" align="left">Purified water</entry><entry namest="col3" nameend="col3" align="left">Qs to 5 g (4 to 4.2 g)</entry></row></tbody></tgroup></table></tables>

Gel preparation:

- It is carried out in the same manner as for Example I. - Benzalkonium chloride and nonoxynol-9 are added at the same time as dimethylpolysiloxane.

Impregnation of the buffer:

- This is identical to that of Example I.

Pharmacological Properties

A-virucidal properties

In a solution infected with the AIDS virus HIV I, it was found, by assay of the activity of reverse transcriptase, an inhibition of the enzymatic agent of the virus: a- with sodium cholate in the following conditions: <tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="3" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="center">Weight% sodium cholate</entry><entry namest="col2" nameend="col2" align="center">% Inhibition reverse transcriptase</entry><entry namest="col3" nameend="col3" align="center">processing time</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="char" char=",">0.04</entry><entry namest="col2" nameend="col2" align="right">70</entry><entry namest="col3" nameend="col3" align="left">15 minutes</entry></row><row><entry namest="col1" nameend="col1" align="char" char=",">0.25</entry><entry namest="col2" nameend="col2" align="right">90</entry><entry namest="col3" nameend="col3" align="left">5 minutes</entry></row><row><entry namest="col1" nameend="col1" align="char" char=",">0.50</entry><entry namest="col2" nameend="col2" align="right">99</entry><entry namest="col3" nameend="col3" align="left">1 minute</entry></row></tbody></tgroup></table></tables> b- by the gel whose composition corresponds to that of Example II: <tables id="tabl0006" num="0006"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="center">gel concentration (volume / volume)</entry><entry namest="col2" nameend="col2" align="center">% Inhibition reverse transcriptase</entry><entry namest="col3" nameend="col3" align="center">processing time</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="right">10⁻⁶</entry><entry namest="col2" nameend="col2" align="right">5</entry><entry namest="col3" nameend="col3" /></row><row><entry namest="col1" nameend="col1" align="right">10⁻⁵</entry><entry namest="col2" nameend="col2" align="right">7</entry><entry namest="col3" nameend="col3" /></row><row><entry namest="col1" nameend="col1" align="right">10⁻⁴</entry><entry namest="col2" nameend="col2" align="right">99</entry><entry namest="col3" nameend="col3" /></row><row><entry namest="col1" nameend="col1" align="right">10⁻³</entry><entry namest="col2" nameend="col2" align="right">100</entry><entry namest="col3" nameend="col3" align="left">less than 2 minutes</entry></row><row><entry namest="col1" nameend="col1" align="right">10⁻²</entry><entry namest="col2" nameend="col2" align="right">100</entry><entry namest="col3" nameend="col3" align="left">less than 2 minutes</entry></row><row><entry namest="col1" nameend="col3" align="justify">(Min: minute)</entry></row></tbody></tgroup></table></tables>

B-bactericidal properties

The gel whose composition corresponds to that of Example II shows, at 32 degrees Celsius, the following bactericidal activity: <tables id="tabl0007" num="0007"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="center">strains</entry><entry namest="col2" nameend="col2" align="center">Antiseptic concentration (v / v)</entry><entry namest="col3" nameend="col3" align="center">Contact time necessary</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Staphylococcus aureus CIP 53127</entry><entry namest="col2" nameend="col2" align="char" char=",">0.5%</entry><entry namest="col3" nameend="col3" align="right">5 min</entry></row><row><entry namest="col1" nameend="col1" align="left">Candida albicans CIP 1180.79</entry><entry namest="col2" nameend="col2" align="char" char=",">5%</entry><entry namest="col3" nameend="col3" align="right">5 min</entry></row><row><entry namest="col1" nameend="col1" align="left">Streptococcus Agalactiae CIP 55,118</entry><entry namest="col2" nameend="col2" align="char" char=",">0.5%</entry><entry namest="col3" nameend="col3" align="right">5 min</entry></row><row><entry namest="col1" nameend="col1" align="left">Neisseria gonorrhoeae CIP 79 18</entry><entry namest="col2" nameend="col2" align="char" char=",">0.1%</entry><entry namest="col3" nameend="col3" align="right">5 min</entry></row><row><entry namest="col1" nameend="col1" align="left">Garnella Vaginalis CIP 7074</entry><entry namest="col2" nameend="col2" align="char" char=",">0.5%</entry><entry namest="col3" nameend="col3" align="right">5 min</entry></row></tbody></tgroup></table></tables>

The bacterial strains mentioned in this table represent species responsible for sexually transmitted vaginal infections.

The minimum antiseptic concentration according to the French Pharmacopoeia is 5% (gram / milliliter) in 15 minutes.

C-Properties Pest Control

At a concentration of 0.5% (gram / milliliter) in water with a 5 minute contact time at 37 DEG C., the gel (the composition of which corresponds to that of Example II) has an immediate antiparasitic effect which drops the population Trichonomas Vaginalis a factor of 1000 at least.