HK1172819A - Topical patch cooling preparation - Google Patents

Description

Topical cooling patch

The present application is a divisional application of the following applications: application date: 12/16/2005; application No.: 200580045816.5(PCT/US 2005/045835); the invention name is as follows: a topical cooling patch.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority of application date to U.S. provisional patent application No.60/641,482, filed 2005, 1,4, the contents of which are incorporated herein by reference, in accordance with 35u.s.c. § 119 (e).

Background

Tissue inflammation is the result of the cross-over of multiple physiological events. Skin inflammation associated with tissue damage can be caused by various skin diseases, such as eczema, psoriasis, seborrheic dermatitis, contact dermatitis, allergic dermatitis, and the like. Inflammation is also associated with tissue damage caused by ultraviolet or thermal burns, attack by certain microorganisms, insect bites, stings, and the like. Inflammation of the deep structures, muscles, tendons, bursa and joints associated with tissue damage can be caused by physical trauma such as sprains, strains, contusions, strenuous exercise, and the like. These inflammations can lead to bursitis, tendonitis, and muscle soreness. Inflammation is also associated with tissue damage due to the following causes; metabolic disorders, such as gout; immune disorders, such as rheumatoid arthritis; or age-related changes, such as osteoarthritis.

Symptoms of inflammation are erythema (redness), edema (swelling), heat, pain and loss of function. The direct consequence of tissue damage is the release of certain chemical substances that act as mediators of inflammation, i.e., these substances cause and intensify the events that cause redness, swelling, pain, and heat. Examples of such chemicals are histamine, 5-hydroxytryptamine and kinins.

Currently, a wide variety of topical patches are used to relieve pain, such as shoulder soreness, back pain, inflammation, and the like. Typical active ingredients of these topical patches are methanol, camphor and peppermint oil as cooling anti-irritants. However, one problem with these cooling agents is their strong odor, which can be unpleasant.

Therefore, there has been a constant interest in developing new topical temperature-barrier compositions that are effective in treating patients suffering from the above conditions.

Relevant documents

U.S. Pat. Nos. 4,296,255; 4,296,093; 4,230,688; 4,226,988, respectively; 4,193,936, respectively; 4,153,679, respectively; 4,150,052; 4,070,496, respectively; 4,070,449, respectively; 4,060,091, respectively; 4,059,118, respectively; 4,034,109, respectively; 4,033,994, respectively; 4,032,661, respectively; 4,020,153, respectively; 5,266,592, respectively; 4,459,425, respectively; 5,773,410, respectively; 6,267,974, respectively; 6,592,884; 5,959,161, respectively; 6,328,982, respectively; 6,359,168, respectively; 6,214,788, respectively; 5,608,119, respectively; 6,769,428, respectively; 6,455,080, respectively; 6,656,456, respectively; 6,821,507, respectively; 6,740,311, 6,677,391; 6,497,859, respectively; 6,769,428 and 6,719,995; japanese patent No. 2004059474; U.S. patent application No.20040067970.

Disclosure of Invention

Topical patches containing an odorless physiological cooling agent and methods of use are provided. The topical patch is formed from an adhesive gel composition on a support, the adhesive gel composition containing an odorless physiological cooling agent, a water-soluble polymer gel, water, and a water holding agent. In using the topical patch preparation, it is applied to the skin surface of a subject and maintained at the site of application for a period of time sufficient to allow an effective amount of the odorless physiological cooling agent to be administered to the subject. The present invention may be used in a variety of applications.

Drawings

Fig. 1 is a cross-sectional view of a topical patch preparation in accordance with one embodiment of the present invention.

Fig. 2 and 3 provide schematic diagrams of a method for manufacturing a topical patch preparation in accordance with one embodiment of the present invention.

Detailed Description

Topical patches containing an odorless physiological cooling agent and methods of use are provided. The topical patch is formed from an adhesive gel composition on a support, the adhesive gel composition containing an odorless physiological cooling agent, a water-soluble polymer gel, water, and a water holding agent. In using the topical patch preparation, it is applied to the skin surface of a subject and maintained at the site of application for a period of time sufficient to allow an effective amount of the odorless physiological cooling agent to be administered to the subject. The present invention may be used in a variety of applications.

Before the present invention is further described, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Where a range of values is provided, it will be understood that each intervening value, to the 1/10 unit of lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to removal of the limits specifically excluded in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

The methods recited herein may be performed in any reasonably possible order for the events recited, as well as the order of the events recited.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the methods and materials now described are preferred.

All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.

It must be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It is also noted that the claims may be designed to exclude any optional elements. Accordingly, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only," and the like, or use of a "negative" limitation with respect to the recitation of claim elements.

The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. In addition, the dates of publication provided may be different from the actual publication dates, which may need to be independently confirmed.

Topical patch

As described above, the present invention relates to a topical patch preparation of an odorless physiological cooling agent. The topical patch preparation of the present invention is characterized by containing an effective amount of an odorless physiological cooling agent in a gel-adhesive base. Figure 1 provides a schematic representation of a topical patch according to the present invention. As can be seen in FIG. 1, the representative topical patch 10 includes a gel-adhesive base 12 present on a carrier 14. All of these components are now described in more detail.

The gel-adhesive binder, which functions as a retention layer, consists of the odorless physiological cooling agent and the adhesive gel binder present, for example, dissolved or dispersed in the binder. "physiological cooling agent" refers to a drug which, when brought into contact with the skin of a subject, imparts a cooling sensation or effect to the subject in a manner similar to the cooling effect of methanol. By "odorless" is meant that the odor of the drug is less irritating than the odor of methanol.

Chemical name	Description of the invention
		Menthol crystal	Natural compounds, strong odor
WS-3	Almost odorless
		WS-23	Almost odorless
Frescolat ML	Faint minty taste

WS-3: (N-ethyl pair)Alkane-3-carboxamide), Millennium Chemcal product

WS-23: (2-isopropyl-N, 2, 3-trimethylbutanamide), product of Millennium Chemical

Frescolat ML: (-) -lactic acidEsters, Haarmann&Reimer product

In certain embodiments, the cooling agent is an acyclic amide, representative acyclic amides include compounds of the formula:

wherein

R₁、R₂And R₃Each is C₁-C₅Alkyl groups, taken together, having a total of at least 3, such as about 3 to 10, including about 5 to 10 carbon atoms; r' is C₁-C₅Alkyl radical, C₁-C₈Hydroxyalkyl, or alkylcarboxyalkyl of up to 8 carbon atoms. In this group, R₁In representative embodiments methyl, ethyl or n-propyl, R₂And R₃One or both of which are branched at the alpha or beta position relative to the carbon atom marked with the x number. In representative embodiments, the temperature reducing agent is N, 2, 3-trimethyl-omega-isopropylbutanamide (also known as WS-23; trimethylisopropylbutanamide, CAS # 51115-67-4).

The above compounds may be prepared by any suitable protocol, a representative protocol being described in U.S. Pat. No.4,296,255.

Other important representative odorless physiological cooling agents include, but are not limited to: linalool, citronellol, hydroxycitronellal, WS-3(Millennium Chemical), Flescolot MGA (Haarman & Reimer), Frescolot ML (Haarmann & Reimer), PMD 38(Takasago), Cootact P (Takasago), and coating Agent 10(Takasago), among others.

The amount of odorless physiological cooling agent present in the adhesive gel base, as described in detail below, is sufficient to administer an effective amount of the cooling agent to a skin surface of a subject when applied thereto. In many embodiments, the odorless physiological cooling agent is present in the adhesive gel base in an amount of about 0.1-15.0% (w/w), sometimes about 0.5-10.0% (w/w), such as about 1.0-8.0% (w/w), including about 2.0-7.0% (w/w).

As described above, the adhesive gel base containing the temperature lowering agent is composed of a water-soluble high molecular weight substance, water and an aqueous agent. In certain embodiments, the adhesive gel binder further comprises a co-solvent, such as an organic co-solvent. The individual components are now described separately in more detail.

Important water-soluble high molecular weight materials include water-soluble polymers, where important polymers include, but are not limited to: gelatin, starch, agar, mannan, alginic acid, polyacrylic acid, sodium polyacrylate, dextrin, methyl cellulose, sodium methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carboxyvinyl polymers, polyvinyl alcohol, polyvinyl pyrrolidone, gum arabic, gum tragacanth, karaya gum, and starch acrylate copolymers or other sodium starch acrylate graft copolymers. Metal salts of these polymers and crosslinked products formed by organic or inorganic crosslinking agents are also contemplated. These water-soluble polymers may be used to exert the properties and characteristics of other starting materials used in the adhesive gel composition, and may be used either singly or in combination of two or more. The content of the water-soluble high molecular weight substance in the adhesive gel base is generally about 0.5 to 20%, for example about 2 to 20% (w/w).

Any suitable water may be used as the water component, but of particular importance are distilled water or ion-exchanged water, etc., which are preferred in many embodiments of the present invention. The amount of water in the gel adhesive is sufficient to provide the gel adhesive with the desired physical properties, to improve the swelling of the stratum corneum or horny layer of the skin, and thereby improve the penetration or penetration capacity of the active agent, wherein the amount of water in the gel composition is generally about 10-80%, for example about 30-60% (w/w).

The water retention agent or agent of the adhesive gel composition of the present invention is any agent that is capable of at least reducing evaporation of water contained in the adhesive gel base, thereby maintaining the water content in the adhesive gel base at an at least substantially, if not constant, level during storage and use of the formulation. One or more water-retaining agents may be used in the compositions of the present invention, wherein the water-retaining agent is present in the adhesive gel base in an amount of about 1 to 70%, for example about 10 to 60% by weight. Suitable water retention or water holding agents include, but are not limited to, one or more multivalent or polyhydroxyl sugars or alcohols, such as glycerol, sorbitol, propylene glycol, diethylene glycol, 1, 3-butanediol, and ethylene glycol, among others.

In addition, the gel binder composition of the present invention may also include a co-solvent, which is typically an organic co-solvent. Examples of important co-solvents include, but are not limited to: n-methyl-2-pyrrolidone, diethyltoluamide, ethanol, methanol, polyethylene glycol (e.g., low molecular weight polyethylene glycols such as PEG 600 or lower, e.g., 500, 400, 300, 200, 100, and the like and blends thereof), isopropyl myristate, and the like. The co-solvent may be comprised of a single component or a combination of two or more components.

Further, in addition to the above-mentioned components, various additives used in a conventional water-soluble patch for topical use, including inorganic substances such as kaolin, bentonite and titanium dioxide; preservatives, such as parabens; anionic, cationic and nonionic surfactants; metallic aluminum crosslinking agents such as aluminum chloride, dried aluminum hydroxide gel and dihydroxyaluminum aminoacetate; oils such as jojoba oil and castor oil; chelating agents, such as EDTA; pH adjusters such as malic acid, tartaric acid and diisopropanolamine; alcohols, such as ethanol; humectants, such as hyaluronic acid, aloe vera extract, and urea; and other fragrances and colorants.

The pH of the gel base composition is generally within a physiologically acceptable range, and the pH may generally be from about 4.0 to 7.0, for example from about 4.0 to 6.0.

As noted above, the adhesive gel composition containing one or more active ingredients is typically disposed on a carrier or backing material. The carrier is generally made of a flexible material that can adapt to the movements of the human body, including, for example, various nonwoven fabrics, woven fabrics, spandex fibers, flannel, or laminates of these materials with polyethylene films, polyethylene terephthalate films, polyvinyl chloride films, ethylene-vinyl acetate copolymer films, polyurethane films, and the like.

In addition to the adhesive gel composition and the carrier layer, the topical patch of the present invention may also include a release film 16 on the surface of the gel layer opposite the backing, which protects the gel layer from the environment. The release film may be of any suitable material, representative release films including polyesters such as PET or PP and the like.

In many embodiments, the patch is contained in a sealed package. Typically, the sealed package is made of packaging material that includes a thin layer that prevents the passage of moisture, oxygen and other agents, i.e., the package includes a moisture/oxygen barrier material. Any suitable barrier material may be used, important barrier materials include metal layers, such as aluminum, and in many embodiments the barrier layer is an aluminum layer. The thickness of such a barrier layer is sufficient to provide the barrier function and is typically about 5-15 μm, usually about 6-10 μm. In many embodiments, the package is a laminate formed by combining the barrier layer with one or more other layers, such as polymer layers, paper layers, and the like. A representative aluminum-containing package that can be used with the patch of the present invention is sold by Dainippon Printing co., Ltd. (Kyoto, Japan).

The topical patch may be made by any suitable protocol. One suitable protocol for making the patch of the present invention includes preparing a gel adhesive paste by uniformly mixing the above ingredients, then applying the paste to a carrier, and then cutting the resulting product to a specified size to obtain the desired topical patch. The resulting topical patch is then heat sealed with a packaging material containing an aluminum layer as described above, typically several sheets in one package, to obtain a sealed topical patch. For a more detailed description of the manufacturing scheme, see U.S. Pat. No.5,827,529, the disclosure of which is incorporated herein by reference.

In one representative manufacturing scheme, the base used in the present invention is prepared by: the above ingredients are blended uniformly into a paste using a mixer using any suitable protocol and then spread onto a substrate or carrier material using a spreader. As mentioned above, the carrier material may be, for example, paper, or a woven or non-woven fabric made of PET or PP or some other polyester fiber. For protection, its surface is subsequently covered with a polyester, for example PET or PP, release film. These steps are illustrated in fig. 2.

As described in more detail below, in representative embodiments, the hydrogel patch composition is self-adhesive, i.e., inherently tacky, and thus can be secured in place over a skin wound, i.e., releasably adhered to and/or around a designated skin wound, without the use of additional adhesives or other means to hold the patch in place. For example, the hydrogel composition matrix itself may be an adhesive.

In a representative embodiment, the hydrogel composition is an adhesive as determined using the Japanese Industrial Standard (JIS) Z-0237 adhesive Strength determination protocol (see, e.g., U.S. patent application No.60/615,320, entitled methods and Compositions for Treating SKin woods, filed on.12/1 of 2004; the contents of which are incorporated herein by reference). A given hydrogel composition is considered an adhesive if it is capable of stopping at least a No.3 size sphere, such as at least about a No.4 size sphere, including at least about a No.5 size sphere, during such a procedure. In certain embodiments, the composition has sufficient adhesion to stop a ball of No.6 or larger, e.g., a ball of No.7 or larger, such as a ball of No.8 or larger, e.g., a ball of No.9 or larger. In certain embodiments, the compositions of the present invention are differentially adhesive, with greater adhesion to inanimate objects than to animate objects.

In other embodiments, the hydrogel patch compositions of the present invention may be held in a fixed position around a skin wound by additional adhesives, such as adhesive backing or the like, or by inherent adhesive properties in combination with a different adhesive means.

Some hydrogel patch compositions may be suitable and used with the present invention. Representative hydrogel compositions suitable for use with the present invention include, but are not limited to, those described in the following patents: PCT international publication: WO 02/078757 and WO 02/078756, and us patents: 5,120,544, respectively; 5,160,328, respectively; 5,270,358; 5,423,737, respectively; 5,476,443, respectively; 5,489,262, respectively; 5,501,661, respectively; 5,827,529; 6,039,940, respectively; 6,096,333, respectively; 6,214,374, respectively; 6,296,869, respectively; 6,348,212, respectively; 6,455,065, respectively; the contents of which are incorporated herein by reference.

The resulting product is then cut to size to obtain the desired topical patch composition. The shape of the patch may vary, with representative shapes including square, rectangular, oval, circular, and the like. The size of the patch may also vary, and in many embodiments ranges from about 1 to 200cm in size²And in many embodiments, from about 10 to 180cm²Typically about 100 and 150cm²E.g. 140cm². The base weight in the final topical patch may be about 300-1500g/m²E.g., about 600-1200g/m². This water-soluble topical patch was then packaged by heat sealing in a packaging material containing an aluminum layer to give the final product shown in fig. 3.

It should be noted that the above manufacturing procedures are merely representative. Any suitable protocol capable of manufacturing the topical patch of the present invention may be used.

Method of using patch

The patch of the present invention may be used for the topical delivery of a cooling agent to a subject, particularly to the skin of the subject. In the practice of the present invention, the patch may be applied to any suitable topical site. Important local sites include, but are not limited to: arms, legs, torso, head, etc. The surface area covered by the topical patch after application must be sufficient to provide the desired amount of drug administration, in many embodiments about 1-200cm²And in many embodiments, from about 10 to 180cm²Typically about 100 and 150cm²E.g. 140cm²。

In representative embodiments, the time period for release of the desired amount of drug is generally no more than about 48 hours, and usually no more than about 24 hours. However, the time that the formulation is held at the application site is, in many embodiments, at least about 30 minutes, and typically at least about 1 hour.

In practicing the methods of the invention, the topical patch may be applied one or more times over a specified period of time, such as during the treatment of a condition, wherein if multiple patches are applied over a specified period of time, the schedule of administration may be daily, weekly, bi-weekly, monthly, etc.

The patch and method described above may be used in any situation where it is desirable to administer a physiological cooling agent to a subject. In addition to its use, topical administration of cooling agents in accordance with the methods of the invention described herein is effective for the treatment of inflammation, pain, and the like, including the diseases described in the introductory portion of this application. Typically, the subject is a "mammal," and these terms are used broadly to describe living organisms belonging to mammals, including the orders carnivore (e.g., dogs and cats), rodentia (e.g., mice, guinea pigs, and mice), and primates (e.g., humans, chimpanzees, and monkeys). In many embodiments, the host will be a human.

In representative embodiments, the methods of the invention are useful for treating disorders. Treatment refers to at least the reduction of symptoms associated with the pathological condition afflicting the host, where reduction is used in a broad sense to refer to a parameter, e.g., symptoms, that is at least reduced in size in relation to the pathological condition being treated and the side effects associated therewith. Thus, treatment also includes situations in which the pathological state, or at least the symptoms associated therewith, is completely inhibited, e.g., prevented from occurring, or is halted, e.g., terminated, such that the host no longer suffers from the pathological state, or at least the symptoms that are characteristic of the pathological state. Thus, treatment includes both curing and controlling the condition.

Reagent kit

Kits are also provided, the kits of the invention comprising at least one or more of the patches described above. The topical patch of the present invention in the kit may be placed in a package as described above. The topical patches of the kit are typically in a separate pouch or similar container in order to preserve the composition of the patch until use. The kits of the present invention also typically include instructions for how to use the patch, which typically include information regarding where the patch is to be used, the schedule of administration, and the like. The instructions are typically recorded on a suitable recording medium. For example, the instructions may be printed on a substrate, such as paper or plastic. Thus, the instructions may be placed within the kit as a package insert, in the label stem of the container of the kit or components thereof (i.e., with the package or secondary package), and the like. In other embodiments, the instructions are provided in the form of an electronically stored data document on a suitable computer readable storage medium, such as a compact disc, floppy disk, or the like.

The following examples and comparative examples are provided by way of illustration and not by way of limitation.

Examples

Examples and comparative examples are given below, but the manufacturing method is not limited thereto.

1. Preparation of topical Patches

A water-soluble polymer topical patch preparation, wherein WS-23 is mixed in the amount of 5% and 7%. WS-23 was mixed homogeneously with the components listed in Table 1 and adjusted to a paste-like state, which was then spread on a PET nonwoven fabric to a weight of 1000g/m²The resulting product was then laminated with PP film and cut to 10cm x 14 cm.

TABLE 1

^*: all values are expressed in% (w/w).

2. Stability data

WS-23 content and stability data for patch cohesive strength in example 01. The experiment was carried out in an environment of 40 ℃ and 75% humidity. The results are shown in Table 2 in comparison with the initial values, which were taken as 100%.

TABLE 2

The adhesive strength measurement method comprises the following steps: japanese Industrial Standard (JIS) Z-0237

3. Activity assay

The topical patches of example 01 and WS-23 were applied to volunteers of patients with shoulder aches, back pain, muscle fatigue pain, and Carpal Tunnel Syndrome (CTS) to study their efficacy.

The WS-23 topical patch of example 01 was applied to the affected area of 4 volunteers for 12 hours.

Pain levels were measured for each subject before and 30 minutes after application.

The results are shown in table 3 below.

TABLE 3

	Initial value	Disorders of the disease	Before application	After application
					Patient 1	JS	Soreness of the shoulder	07	05
Patient 2	MY	Back pain	06	04
					Patient 3	TA	Muscular fatigue and pain	07	02
Patient 4	SS	CTS	08	06

Pain level:

10: disability, pain must be dealt with.

08: serious, not capable of being absorbed, except simple things, not capable of doing things.

06: moderate, but can continue some physical activity.

04: can be tolerated and can be neglected somewhat.

02: mild, a potentially mild pain was observed.

00: has no pain.

It is apparent from the above results and discussion that the present invention provides an important novel cooling sensation anti-irritation topical patch composition that provides benefits over current patches, including the absence of odor. Accordingly, the present invention represents a significant contribution to the art.

All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.

Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

Claims (22)

1. A topical patch preparation comprising:

an adhesive gel composition containing an odorless physiological cooling agent; and

and (3) a carrier.

2. The topical patch preparation according to claim 1, wherein said odorless physiological cooling agent is an acyclic amide.

3. The topical patch preparation according to claim 2, wherein said acyclic amide is represented by the following chemical formula:

wherein R is₁’、R₁、R₂And R₃Are all C₁-C₅An alkyl group.

4. The topical patch preparation according to claim 3, wherein said acyclic amide is N, 2, 3-trimethyl-2-isopropylbutanamide.

5. The topical patch preparation according to claim 4, wherein said N, 2, 3-trimethyl-2-isopropyl butanamide is present in said adhesive gel composition in an amount of about 0.1-15.0% (w/w).

6. The topical patch preparation of claim 1, wherein said adhesive gel composition comprises:

a water-soluble polymer gel;

water; and

a water-retaining agent.

7. The topical patch preparation according to claim 6, wherein said water is present in an amount of about 10-80% (w/w).

8. The topical patch preparation according to claim 1, wherein said adhesive gel composition has a pH of about 4.0 to about 7.0.

9. The topical patch preparation of any one of claims 1 to 8, wherein said patch further comprises a release film on the surface of said adhesive gel composition.

10. A topical patch preparation comprising:

(a) an adhesive gel composition having a pH in the range of about 4.0 to 7.0 comprising:

(1) n, 2, 3-trimethyl-2-isopropylbutanamide in an amount of about 0.1-15.0% (w/w);

(2) a water-soluble polymer gel;

(3) water in an amount of about 10-80% (w/w); and

(4) a water-retaining agent; and

(b) and (3) a carrier.

11. The topical patch preparation according to claim 10, wherein said N, 2, 3-trimethyl-2-isopropyl butanamide is present in an amount of about 0.5-10% (w/w).

12. The topical patch preparation according to claim 10, wherein said water is present in an amount of about 20-70% (w/w).

13. The topical patch preparation according to claim 12, wherein said water is present in an amount of about 30-60%.

14. The topical patch preparation according to claim 10, wherein said pH range is about 4.0-6.0.

15. A topical patch preparation comprising:

(a) an adhesive gel composition having a pH in the range of about 4.0 to 6.0 comprising:

(1) n, 2, 3-trimethyl-2-isopropylbutanamide in an amount of about 0.5-10.0% (w/w);

(2) a water-soluble polymer gel;

(3) water in an amount of about 30-60% (w/w);

(4) a water-retaining agent;

(b) and (3) a carrier.

16. A method of delivering an odorless physiological cooling agent to a subject, the method comprising:

(a) applying a topical patch to a skin surface of a subject, the topical patch comprising:

(1) an adhesive gel composition containing the odorless physiological cooling agent; and

(2) a carrier;

(b) maintaining the topical patch on the skin surface for a period of time sufficient to deliver the odorless physiological cooling agent to the subject.

17. The method according to claim 16, wherein the odorless physiological cooling agent is an acyclic amide.

18. The method according to claim 17, wherein said acyclic amide is present in said adhesive gel composition in an amount of about 0.1-15.0% (w/w).

19. A kit, comprising:

(a) a topical patch preparation comprising

(1) An adhesive gel composition comprising an effective amount of a physiological cooling agent; and

(2) a carrier; and

(b) instructions for using the formulation.

20. A kit according to claim 19, wherein the kit contains a plurality of said topical patches.

21. The kit according to claim 20, wherein said plurality of topical patches are in separate containers.

22. The kit of claim 21, wherein said separate container is a sealed bag.