Micro-encapsulated topical analgesic for pain relief and sleeve comprising it

<u>Field of the Invention</u>

0001The present invention relates to a topical preparation used to reduce or treat pain, and a new sleeve used for application of topical preparations. The active ingredients of the topical preparation are micro-encapsulated to provide extended release of the active ingredients and improved feel and working characteristics of the preparation. The micro-encapsulated active ingredients are especially useful in connection with preparations applied via sleeves or patches, however, the encapsulated topical analgesic may be administered in the form of a cream, ointment, balm, stick, patch, sleeve or other forms used for topical application.

<u>Background of the Invention</u>

0002Topical preparations in the form of analgesics are widely used to relieve pain. They are typically used by consumers with muscle or joint pains, soreness, sprains or strains, and are used by consumers unable to tolerate oral analgesics, for example users who suffer from ulcers or who are pregnant, or consumers desiring topical analgesia as an adjunct to oral medication. Topical analgesics typically come in the form of ointments, lotions, solutions and creams that are applied to the affected area. They relieve the pain and stiffness of arthritis, rheumatism, muscle and joint soreness, back pain, bursitis, tendonitis, muscle strains and sprains, bruises and cramps. In more recent years, topical analgesics have been administered via adhesive patches, particularly in cases of back aches and soreness.

0003Although topical analgesics are effective in providing prompt pain relief, their effect is not always long lasting. Some topical analgesics must be reapplied often because the effect wears off quickly. Topical analgesics may also be rubbed off during daily activities or wiped off by the rubbing of clothes against the affected area. Recently, patches consisting of topical analgesics have been used to realize longer lasting pain relief, such as described in U.S. Patent No. 6,277,401, which teaches a patch for drug delivery through a foam layer. Many other topical analgesic patches are simply a layer of adhesive impregnated with a topical analgesic formulation and a layer of gauze or other fabric. These patches apply the active ingredients in the form of a semi-flexible patch that holds the analgesic and protects it from being worn off during daily activities. Although usually having longer efficacy than topical application of creams and ointments, the analgesic patches only minimally extend release of the active ingredients and so the effectiveness of the analgesic wears off quickly. Moreover, the patches have a number of draw backs. Consumers do not like the feel of the patches because they feel wet, often have strong menthol odors, and do not adhere well to joints. The application of the patches can also be difficult. Additionally, the patches do not stay in place, except when used on flat body areas such as the back, which are not subject to substantial movements or flexing actions. Finally, use of the patches on hirsute body areas may result in additional pain due to unintended hair extraction when the patch is removed.

0004Despite the existence of topical analgesic creams, lotions and sticks and topical analgesics in the form of patches in the prior art, there is room for improvement. None of the prior art discloses employing a micro-vesicle system for administration of the active ingredients in order to provide for extended release of the active ingredient resulting in more effective treatment. Use of the micro-vesicle technology may also reduce the wet and soggy feeling associated with the application of analgesic patches, because less ointment is required to achieve the desired effect. Moreover, the prior art does not disclose the use of topical analgesics in the form of sleeves or joint-specific applications so that the topical preparation stays in place through the full range of motion and repeated bending of a joint, and without the requirement of an adhesive to hold the patch in place.

0005A variety of methods are currently used to administer topical analgesics for pain relief. The methods typically involve the topical administration of analgesics to the affected area. Some products are administered in the form of creams, lotions, ointments and sticks. Although these products provide faster and more localized pain relief than the oral administration of drugs, the relief may be short lived if the analgesic is not long lasting or wears off quickly. Other products include patches impregnated with topical or external analgesics that are applied to the target area. Although these products provide longer lasting pain relief by holding the active ingredients, patches still do not provide substantially extended release of active ingredients and do not suitably adhere to joint areas. Removal of adhesive patches may also produce consumer discomfort. A more effective and long lasting method of administering these products is needed.

0006The current invention consists of a product for topical administration of extended release substances for relieving pain. The invention comprises micro-encapsulation of one or more active ingredients to provide extended release of the active ingredient in the form of a cream, lotion, ointment or stick. Alternatively, the invention may be in the form of a flexible patch or sleeve, or joint specific application, providing an extended release active formulation.

<u>Summary of the Invention</u>

0007The present invention recognizes and addresses the foregoing disadvantages, and others, of prior art compositions and methods.

0008Briefly, the present invention is a novel topical preparation used to treat pain and improve j joint function. The topical preparation consists of micro-encapsulated active ingredients to provide extended release of the active ingredients. The micro-encapsulated topical preparation may be administered in the form of a cream, lotion, solution, ointment, balm, stick, patch or other forms used for topical application. The present invention may also be used in connection with a sleeve so that the topical preparation is easy to apply and stays in place during the full range of motion and repeated bending of a joint, and without the requirement of an adhesive.

0009One novel aspect of the topical preparation of the present invention is the use of micro-encapsulated active ingredients for extended release of the active ingredients and long lasting relief.

0010Another novel aspect of the invention is the use of micro-vesicle technology to reduce the unpleasant wet and soggy feelings associated with the application of analgesic patches.

0011Another novel aspect of the present invention is the use of topical analgesics in the form of sleeves so that the topical analgesic is suitably positioned at joint areas and stays in place.

0012Another novel aspect of the present invention is the use of topical analgesics carried in the form of sleeves so that the topical analgesic carrier may be removed without producing the consumer discomfort of an adhesive carrier.

0013More particularly, it is an object of the present invention to provide a topical preparation with micro-encapsulated active ingredients in the form of a sleeve which is long lasting, easy to apply, and securely positioned at joint areas.

0014Additional objects and advantages of the invention will be set forth in part in the following description, or may be obvious from the description, or may be learned through the practice of the invention.

<u>Brief Description of the Drawings.</u>

0015Certain aspects of the invention may be better appreciated with reference to the following illustrations:

0016Figure <b>1</b> is a top plan view of a sleeve according to the present invention with patch area adapted to receive a topical analgesic preparation in the form.

0017Figure <b>2</b> is a side plan view of the sleeve of Figure <b>1.</b>

0018Figures <b>3a</b> and <b>3b</b> show the sequential application of the sleeve to the wrist.

0019Figures <b>4a, 4b</b> and <b>4c</b> show the sequential application of the sleeve to the elbow.

0020Figure 5 illustrates a flattened knit sleeve with an insert.

<u>Detailed Description of the Invention.</u>

0021This invention teaches a topical preparation for pain relief in humans and a flexible sleeve for application of topical preparations. The topical preparation contains a micro-encapsulated active ingredient formulation to provide extended release of the active ingredients for long lasting pain relief and improved touch and feel of the preparation to the consumer. The topical preparation may be in the form of a stick, cream, lotion, solution or ointment applied to the affected area. Alternately, the topical preparation may be administered in the form of an impregnated patch or sleeve. The micro-encapsulation of the active ingredient of the topical preparation provides immediate, and long lasting pain relief. In addition, the use of micro-encapsulated active ingredients tends to improve the feel of the entire preparation. The topical preparation may be used to reduce or treat pain, soreness or stiffness associated with arthritis, rheumatism, muscle and joint soreness, back pain, bursitis tendonitis, muscle strains and sprains, bruises and cramps.

0022A variety of topical analgesics may be used in connection with the present invention. The most common topical analgesics are local anesthetics and anti-inflammatories such as salicylates or NSAIDS, and counter-irritants including capsaicin and aromatic compounds. Anesthetics such as lidocaine, that act on local sensory afferents, are intended to totally block pain receptors and numb the area of application. Salicylates and NSAIDS such as ibuprofen, are anti-inflammatory compounds that inhibit pain and inflammation and are generally taken internally. Counter-irritants and aromatics, especially terpenes, are substances such as menthol, oil of wintergreen, camphor, eucalyptus, mustard plasters and turpentine oil, that mask sensations of pain by stimulating local pain afferents and thereby creating a feeling of cold or heat over the affected area. Capsaicin is a natural ingredient found in cayenne peppers. Capsaicin is believed to operate in an anesthetic fashion by depleting Substance-P from sensory afferents and thereby suppressing transmission of pain to the brain. Menthol is a compound obtained from peppermint oils, or other mint oils, or made synthetically. Menthol has local anesthetic and counterirritant qualities.

0023The preferred active ingredient of the present invention is menthol or menthol/menthyl derivatives, such as 1-menthol. Effective amounts of menthol range from 1.25% to 16% by weight of the preparation. Alternately, an effective amount of menthyl lactate may be used, usually between about 0.5% to 20% by weight of the preparation. Capsaicin, or other capsaicinoids, vanilloids, or vanillyl butyl ether, may also be used. The effective amount of capsaicin ranges from 0.025% to 0.25% by weight of the preparation.

0024The base formula can be any suitable carrier, anhydrous, water-based, an emulsion of either oil-in-water or water-in-oil, or alcohol. Additional or alternative ingredients may be used in the composition of the present invention, including, the external analgesic ingredients or combinations recognized in the Food and Drug Administration's External Analgesic Drug Products for Over-The-Counter Human Use; Tentative Final Monograph, published at 48 Federal Register, pp.5852-5869, February 8, 1983.

0025The form of furnishing the topical analgesic is novel to the field because it provides the active ingredient in a micro-encapsulated form which provides for extended release of the active ingredient and reduces the soggy wet feeling when the topical analgesic is held in the form of a patch. Micro-encapsulation can be achieved through liposome or NOVASOMES® brand technology. The preferred technology for micro-encapsulation is liposome based technology, without the use of phospholipids. This technology is used with products supplied by Novavax Inc. of Buena, New Jersey under the NOVASOMES® brand. However, other methods of micro-encapsulation may be used. NOVASOMES® based technology generally uses non-phospholipid vesicles made from amphiphiles using a manufacturing process, in which drugs can be encapsulated for oral or topical delivery into the body. Amphiphiles include fatty alcohols and acids, ethoxylated fatty alcohols and acids, glycol esters of fatty acids, glycerol fatty acid anmono and diesters, ethoxylated glycerol fatty acid esters, glyceryl ethers, fatty acid diethanolamides and dimethyl amides, fatty acyl sarcosinates, alkyds and phospholipids. NOVASOMES® brand vesicles are preferred over traditional phospholipid based liposomes because they are more stable. NOVASOMES® brand vesicles are shaped like tiny balloons and formed by approximately 5-7 concentric membrane-like outer walls. They are typically 0.3 - 0.7 microns in diameter. They are stable in the presence of electrolytes and within a pH range of 2-10.

0026The topical preparation of the present invention may be provided in the form of a cream, lotion, solution, ointment, stick, patch or sleeve. The micro-encapsulation of the active ingredients in a preparation administered using a patch provides for longer lasting relief which does not feel as wet as typical topical analgesic patches. Optionally, the topical preparation may be administered in the form of a sleeve. As such, the sleeve maybe used on joints such as the knees or wrist and other areas where a patch is difficult to keep in place. The material such as foam, hydrogel, nonwoven fabric, knitting or weaving of the patch or sleeve can be of any type, such as those commonly used in the art in connection with analgesic patches commonly available under the ICY HOT® brand from Chattem, Inc., under the DURA PATCH™ brand from U.S. Dermatologics, Inc., under the THERMO PATCH™ brand from LecTec Corporation, as the MENTHOLATUM PAIN PATCH™ from the Mentholatum Co., or as the TIGER BALM PATCH™ from Haw Par Healthcare, Ltd. Preferably, the sleeve material is light and flexible, or non-occulsive. In addition to holding the topical analgesic in place, another advantage of this invention is the added benefit of joint-specific applications such as joint-specific sleeves that provide support of a joint so that the pain is reduced as a result of compression, restricted range of motion, or mechanical support.

0027Referring now to the drawings, Figure 1 is a top plan view of a preferred embodiment of the analgesic sleeve <b>10</b> according to the present invention. The sleeve <b>10</b> comprises an interior side <b>11</b> (shown in figure <b>4a</b>); an exterior side <b>12</b>; first and second welts <b>13a, 13b</b> forming first and second end sections; first and second transition areas <b>14a, 14b</b> interior of the end sections; and a body <b>20</b> having a therapeutic section such as patch <b>15</b> (shown in figure 4a) containing the active ingredients located on the interior side <b>11</b> of the sleeve <b>10</b>. In a preferred use, the sleeve <b>10</b> generally defines a lumen or tubular passage, having a wall formed of a flexible and elastic material with a patch area <b>15</b> that holds the micro-encapsulated topical analgesic. This sleeve <b>10</b> may be advantageously used on joints, such as the elbows, knees, ankles or wrists. The sleeve <b>10</b> is preferably knit from a combination of conventional yams and specialty moisture management yams. Fibers such as Sorbtek from Unifi, Technofine from Gelanots, and 4DG from Fiber Innovative Technology, Inc. may be employed for moisture management. Typically, approximately one half of the circumference of a sleeve <b>10</b> will be composed of moisture management yams and dosed or impregnated with the preparation comprising one or more topical analgesics, preferably in micro-encapsulated form.

0028Figure 2 is a side plan end view of a preferred embodiment of an analgesic sleeve <b>10</b> according to the present invention. As in Figure 1, the sleeve <b>10</b> defines a lumen, with a wall formed of a flexible material having a patch <b>15</b> that holds the micro-encapsulated topical analgesic. However, this sleeve <b>10</b> also has a thumb cavity <b>16</b> in first transition area <b>14a</b> to secure the sleeve <b>10</b> in place over the hand and wrist. This configuration is particularly well-suited for the management of carpal tunnel syndrome, or repetitive motion injury of the forearm and wrist. The transition areas <b>14a, 14b</b> and welts <b>13a, 13b</b> at each end of the sleeve <b>10</b> are not generally comprised of moisture management yarns impregnated with analgesic preparations. The sleeves <b>10</b> illustrated are particularly sized for application to a wrist or small elbow, and additional sizes maybe appropriately manufactured for knees, larger elbows, and to cover the usual range of dimensions of the human body. Thus, in a stretched or extended state, the lumen of the sleeves should accommodate a human extremity, such as an arm or leg. Furthermore, the moisture management system need not be yarn based, but may comprise a hydrogel, foam or other material held in place by a sleeve 10 of any suitable material including nonwovens, and especially stretchable nonwoven fabrics.

0029The sleeve <b>10</b> according to the present invention should fit snuggly against the skin so that the patch <b>15</b> is in sufficient contact with the affected arca to bc effective. If the sleeve <b>10</b> is too loose, the active ingredients of the patch 15 may not have sufficient contact with the affected area to be effective, and so in a relaxed state, the sleeve should effectively contact the patch to the affected area of the human extremity received within the sleeve. However, if the sleeve<b>10</b> is too tight it will cause discomfort to the affected area. For user comfort and support, a joint specific sleeve <b>10</b>, when appropriately sized, may optionally be designed to provide a compression of about 3-40 mmHG and preferably about 7-30 mmHG. The presently preferred compression of the sleeve <b>10</b> is 10- 15 mm Hg. The wearer may receive pain relief or improved joint function through action of analgesic preparations or compression, or both.

0030The sleeve <b>10</b> is preferably manufactured in various sizes to accommodate the widest range of human limb circumferences while holding the patch <b>15</b> of the sleeve <b>10</b> in contact with the skin. For example, a large sleeve <b>10</b> that expands to fit 8" to 24" in circumference is best used for knees, large ankles and elbows. A small sleeve 10 that expands to fit 5" to 12" in circumference is best used for wrists, small ankles and elbows.

0031A preferred embodiment of the sleeve <b>10</b> is formed from a continuously knit fabric bandage roughly in the form of a tube sock. The dimensions of a sleeve <b>10</b> according to this invention will typically provide a patch <b>15</b> area of at least about four (4) inches by two (2) inches in the relaxed condition or about five (5) inches by four (4) inches in the stretched condition. The longer welts <b>13a, 13b</b> at each end of the sleeve <b>10</b> keep the garment from rolling down, slipping or moving when subjected to typical ranges of joint motion. For this purpose, the welts 13a, 13b have incorporated in them coated or uncoated spandex yams or other similar elastic yams.

0032The thumbhole cavities <b>16</b> allow the user to apply the sleeve <b>10</b> to the hand or the portion of the wrist closest to the hand by cutting the sleeve <b>10</b> as designated on the thumbhole cutout <b>18.</b> The user may then orient the sleeve with her/his thumb through the thumb cavity <b>16</b>. Two thumbhole cutouts <b>18</b> positioned 180 degrees from one another are provided on each sleeve <b>10</b> to allow the user to apply the sleeve <b>10</b> to either hand and orient the patch <b>15</b> to either the top or bottom portion of the hand or wrist. Alternatively, the sleeve <b>10</b> may be manufactured with two pre-cut reinforced thumb cavities <b>16</b> that may be used as a thumb hole. The reinforced thumb cavities <b>16</b> are preferably provided 180 degrees from one another to allow the user to apply the sleeve 10 to either hand and orient the patch <b>15</b> to either the top or bottom portion of the hand or wrist.

0033When made of knit fabric, the sleeve <b>10</b> is preferably constructed of 72% nylon and 10% spandex/lycra and 18% SORBTEK® brand synthetic fiber. The absorbent fiber is placed in the patch area <b>15</b> for maximum efficacy. This results in a flexible, breathable sleeve <b>10</b> that is comfortable for the user. The patch area <b>15</b> is centered longitudinally on the sleeve <b>10</b>. The welts <b>13a, 13b</b> are preferably knit with nylon and spandex yams at the ends of the sleeve <b>10</b>. Each welt <b>13</b> is preferably 22 - 28mm long in its relaxed state. The two thumbhole cut outs <b>18</b> are preferably knit into the first transition area <b>14a</b> of each sleeve <b>10</b> in a reinforced area which is approximately 20mm long x 25mm wide. Preferably, black or colored yam is stitched in the center of each thumbhole cut out <b>18</b> to guide the consumer to slit the sleeve <b>10</b> if a thumbhole is necessary.

0034The illustrated sleeve <b>10</b> may be knit on a 400 needle circular knitting machine. The knitting pattern on the body <b>20</b> of the sleeve <b>10</b> is a 3 x 2 rib pattern with three raised stitches and two recessed stitches forming longitudinal ribs in the sleeve. The patch area <b>15</b> contains the absorbent yarn, preferably SORBTEK™ color PMS 30054 (blue)/Unifi color 4895H Sorbtek Blue, plated with nylon. The knitting pattern of the patch area <b>15</b> is an 8 x 7 rib pattern. The welts <b>13a, 13b</b> are knit with nylon and 210 denier Spandex yams at each end of the sleeve <b>10.</b> Each welt <b>13a</b>, <b>13b</b> is about an inch long in the relaxed state. Welts <b>13a, 13b</b> are knit in a 1 x 1 ribbed pattern. In the preferred embodiment of a smaller sleeve for use on wrists and small elbow joints, there are two thumbhole cut outs <b>18</b> knit into the transition areas <b>14</b> of each sleeve <b>10</b> in a reinforced area approximately 20mm long x 25mm wide. A line of knitting of colored or black yarn is put in the center of each thumbhole cut out 18 to show the consumer where to slit the sleeve <b>10</b> if the thumbhole is desired. The line of knitting is about 15mm long in the transverse direction across the sleeve <b>10</b>, and is centered longitudinally and transversely within the reinforced thumbhole cut outs <b>18</b>. The top edge of the thumbhole cut outs <b>18</b> is 33mm from the edge of the sleeve <b>10</b> including the welt <b>13</b>. Both thumbhole cut outs <b>18</b> are positioned at the same end of the sleeve <b>10</b>. The longitudinal centerline of the thumbhole cut outs <b>18</b> is aligned with the longitudinal edge of the patch <b>15</b> on each side of the patch <b>15</b>. Thumbhole cut out <b>18</b> knitting pattern is a positive stitch.

0035After a knit sleeve <b>10</b> has been manufactured, the sleeve <b>10</b> is preferably positioned with its interior <b>11</b> facing outward, and the exterior surface <b>12</b> being flatly collapsed against itself. An insert <b>22,</b> preferably made from about 10ml PVC, is placed between the upper and lower portions of the exterior surface <b>12</b> to provide shape to the flattened and inside-out sleeve <b>10</b>. When positioned in this fashion, the patch area <b>15</b> should be substantially on the top side of the PVC insert <b>22,</b> and the portion of the body <b>20</b> without the absorbent yarn forming the patch area should be positioned beneath the PVC insert <b>22</b>. The PVC insert <b>22</b> is positioned in this fashion beneath the patch area <b>15</b> of the body <b>20</b> of the sleeve <b>10</b> to facilitate the dispensing of the topical analgesic, in liposome form, onto the patch, and to some extent to keep the topical analgesic contained and concentrated. Even so, there is generally some migration of the topical analgesic into yams other than those forming the patch area <b>15.</b> A typical dosing of about two grams of topical analgesic in liposome form is applied onto the patch area <b>15.</b> The particular formulation of the topical analgesic and materials used for the patch area <b>15</b> may affect the preferred dosage amounts. For a smaller sleeve, the PVC insert <b>22</b> is preferably about 10" long and 2½" wide at its center and tapered at both ends to a 1¾" straight end perpendicular to the sides. The PVC insert <b>22</b> may be perforated or otherwise scored across the center to allow for easier folding. This permits the sleeve <b>10</b> to be readily folded transversely across the center along the perforations in the PVC insert <b>22</b>, with the patch area <b>15</b> treated with topical analgesic forming the inside of the fold. When folded, the ends of the sleeve <b>10</b> should match, and the patch area <b>15</b> should be folded upon itself. The sleeve <b>10</b> is then inserted into a pouch and sealed to maintain the active ingredients. The pouch is preferably formed of a plastic and foil laminate film for this purpose, and for consumer convenience.

0036Referring now to figures 3a, 3b, 4a, 4b and 4c in the preferred embodiment, the sleeve <b>10</b> is packaged and reaches the consumer both folded and "inside out." Thus, when the sleeve <b>10</b> is removed from its pouch and unfolded, the portion of the sleeve <b>10</b> that contains the patch 15 treated with analgesic is inside out on the "interior" side <b>11</b> of the sleeve <b>10</b> and visible to the consumer. When applying a sleeve <b>10</b> to the wrist, the consumer first removes the PVC insert <b>22</b>, and then cuts a slit on a thumbhole cut out <b>18</b> as shown in figure 3a, thereby creating a thumb hole <b>16.</b> The consumer then applies the sleeve <b>10</b> by pulling the thumb hole <b>16</b> over the thumb and the sleeve <b>10</b> over the affected area while turning the sleeve <b>10</b> inside out so that the patch area <b>15</b> is positioned on the area of the wrist where the analgesic is desired.

0037As shown in figures 4a, 4b and 4c, when applying the sleeve <b>10</b> to the arm, elbow, leg, knee or ankle, the consumer first pulls the sleeve <b>10</b> adjacent to the affected area while the portion of the sleeve <b>10</b> that contains the analgesic treated patch area <b>15</b> is inside out on the "interior" side <b>11</b> of the sleeve <b>10</b> and visible to the consumer. The first welt <b>13a</b> of the sleeve is positioned next to the affected area, and the remainder of the sleeve <b>10</b> is opposite the first welt <b>13a</b> from the affected area as shown in figure 4a. Once the sleeve <b>10</b> is in position, the consumer rolls the second welt <b>13b</b> of the sleeve <b>10</b> over, leaving the first welt <b>13</b>a very nearly in the same position while the inside out sleeve is reversed so that the portion of the sleeve <b>10</b> that contains the analgesic patch <b>15</b> is left on the interior side <b>11</b> of the sleeve <b>10</b> and is placed over the affected area coming into contact with the skin as shown in figures 4b and 4c. It is anticipated that in many cases the affected area will be in proximity to joints such as wrists, elbows, knees and ankles.

0038The present sleeve design may also be utilized in wound care to apply medication to a wound, particularly on the arms and legs of a patient.

0039The topical analgesics of the invention are further illustrated by means of the following illustrative embodiments, which are provided for the purpose of illustration only and are not meant to limit the invention to the particular components and amounts disclosed. The following examples show composition of preferred embodiments of topical analgesic formulations.

0040Example 1 below discloses a micro-encapsulated topical preparation comprising 16% menthol Novasomes solution. The solution is a white, smooth solution with the following specifications, stability data and ingredients:

<u>Example 1</u>

Specifications

0041pH = 5.0 - 8.0    Visc = 1000 - 3000 cps    Assay Menthol = 15.7% - 16.8%    Spec gravity = 0.95000 - 0.9900 <tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col1" align="left"><b>Ingredients</b></entry><entry namest="col2" nameend="col2" align="left"><b>Percent By Weight</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Deionized Water</entry><entry namest="col2" nameend="col2" align="center">48.0-50.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Menthol USP</entry><entry namest="col2" nameend="col2" align="center">15.0-17.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Diisopropyl Adipate</entry><entry namest="col2" nameend="col2" align="center">12.0-14.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl Monostearate</entry><entry namest="col2" nameend="col2" align="center">8.0-10.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Diethylene Glycol mono ethyl ether</entry><entry namest="col2" nameend="col2" align="center">4.0-6.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Polysorbate 80</entry><entry namest="col2" nameend="col2" align="center">2.0-3.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl Dilaurate</entry><entry namest="col2" nameend="col2" align="center">2.0-3.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Soya sterol</entry><entry namest="col2" nameend="col2" align="center">1.0-3.0</entry></row><row><entry namest="col1" nameend="col1" align="left">PEG-150 stearate</entry><entry namest="col2" nameend="col2" align="center">0.5-1.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetyl Alcohol</entry><entry namest="col2" nameend="col2" align="center">0.5-1.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Phenoxyethanol</entry><entry namest="col2" nameend="col2" align="center">0.3-0.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Methylparaben</entry><entry namest="col2" nameend="col2" align="center">0.1-0.3</entry></row><row><entry namest="col1" nameend="col1" align="left">Disodium EDTA</entry><entry namest="col2" nameend="col2" align="center">0.05-0.15</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Xanthan Gum</entry><entry namest="col2" nameend="col2" align="center">0.005-0.01</entry></row></tbody></tgroup></table></tables>

0042Example 2 below discloses a micro-encapsulated topical analgesic concentrate comprising 32% menthol Novasomes solution. The solution is white, smooth solution with the following specifications, stability data and ingredients:

<u>Example 2</u>

Specifications

0043pH = 6.5 - 8.5    Visc = 5000 - 8000 cps    Assay Menthol = 30.4% - 33.86%    Spec gravity = 0.9555 - 0.9755 <tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Ingredients</entry><entry namest="col2" nameend="col2" align="left"><b>Percent By Weight</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Deionized Water</entry><entry namest="col2" nameend="col2" align="center">25.0-27.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Menthol USP</entry><entry namest="col2" nameend="col2" align="center">31.0-33.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Diisopropyl Adipate</entry><entry namest="col2" nameend="col2" align="center">15.0-17.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Diethylene Glycol mono ethyl ether</entry><entry namest="col2" nameend="col2" align="center">4.0-6.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl Monostearate</entry><entry namest="col2" nameend="col2" align="center">2.5-3.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Polysorbate 80</entry><entry namest="col2" nameend="col2" align="center">2.0-3.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl Dilaurate</entry><entry namest="col2" nameend="col2" align="center">2.0-3.0</entry></row><row><entry namest="col1" nameend="col1" align="left">PEG-150 stearate</entry><entry namest="col2" nameend="col2" align="center">.5-1.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetyl Alcohol</entry><entry namest="col2" nameend="col2" align="center">.5-1.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Soya sterol</entry><entry namest="col2" nameend="col2" align="center">.4-.6</entry></row><row><entry namest="col1" nameend="col1" align="left">Phenoxyethanol</entry><entry namest="col2" nameend="col2" align="center">.3-.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Methylparaben</entry><entry namest="col2" nameend="col2" align="center">.1-.3</entry></row><row><entry namest="col1" nameend="col1" align="left">Disodium EDTA</entry><entry namest="col2" nameend="col2" align="center">.05-.15</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Xanthan Gum</entry><entry namest="col2" nameend="col2" align="center">0.005-.01</entry></row></tbody></tgroup></table></tables>

0044This concentrate is intended to be diluted to the level set by the FDA Tentative Monograph described above.

0045Yet another similar Novasomes formulation is disclosed in Example 3 below with both menthol and menthyl lactate: <tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row rowsep="1"><entry namest="col1" nameend="col1" align="left"><b>Ingredients</b></entry><entry namest="col2" nameend="col2" align="left"><b>Percent By Weight</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Deionized Water</entry><entry namest="col2" nameend="col2" align="center">38.0-42.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Menthol USP</entry><entry namest="col2" nameend="col2" align="center">15.0-17.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Menthyl Lactate</entry><entry namest="col2" nameend="col2" align="center">15.0-17.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Diisopropyl Adipate</entry><entry namest="col2" nameend="col2" align="center">12.0-17.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl Monostearate</entry><entry namest="col2" nameend="col2" align="center">2.5-7.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Diethylene Glycol mono ethyl ether</entry><entry namest="col2" nameend="col2" align="center">2.5-5.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl Dilaurate</entry><entry namest="col2" nameend="col2" align="center">2.0-3.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Polysorbate 80</entry><entry namest="col2" nameend="col2" align="center">1.5-2.5</entry></row><row><entry namest="col1" nameend="col1" align="left">PEG-150 stearate</entry><entry namest="col2" nameend="col2" align="center">0.5-1.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Soya sterol</entry><entry namest="col2" nameend="col2" align="center">0.4-0.6</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetyl Alcohol</entry><entry namest="col2" nameend="col2" align="center">0.4-1.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Phenoxyethanol</entry><entry namest="col2" nameend="col2" align="center">0.3-0.5</entry></row><row><entry namest="col1" nameend="col1" align="left">Methylparaben</entry><entry namest="col2" nameend="col2" align="center">0.1-0.3</entry></row><row><entry namest="col1" nameend="col1" align="left">Disodium EDTA</entry><entry namest="col2" nameend="col2" align="center">0.05-0.15</entry></row><row><entry namest="col1" nameend="col1" align="left">Xanthan Gum</entry><entry namest="col2" nameend="col2" align="center">0.005-0.1</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="center">0.1-0.25</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Citric Acid (optional)</entry><entry namest="col2" nameend="col2" align="center">about 0.05</entry></row></tbody></tgroup></table></tables>

0046While preferred embodiments of the invention have been described above, it is to be understood that any and all equivalent realizations of the present invention are included within the scope and spirit thereof. Thus, the embodiments depicted are presented by way of example only and are not intended as limitations upon the present invention. While particular embodiments of the invention have been described and shown, it will be understood by those skilled in the art that the present invention is not limited thereto since many modifications can be made.