WO2011118604A1

WO2011118604A1 - Hydrous adhesive patch

Info

Publication number: WO2011118604A1
Application number: PCT/JP2011/056896
Authority: WO
Inventors: 尚久川村
Original assignee: ニプロパッチ株式会社
Priority date: 2010-03-23
Filing date: 2011-03-23
Publication date: 2011-09-29
Also published as: JP2016014052A; TWI506117B; TW201139605A; JPWO2011118604A1

Abstract

Disclosed is a hydrous adhesive patch which contains a drug, has excellent re-adhesion, and is less painful when peeled off the skin. The disclosed hydrous adhesive patch is provided with a support body and an adhesive layer disposed on said support body. The adhesive layer is a preparation of a drug, water (at no more than 30% of the total mass of the adhesive layer), and polyhydric alcohols (at no less than 40% of the total mass of the adhesive layer). The polyhydric alcohols optimally include glycerin. The adhesive layer further contains an inorganic powder, and the sum of the amounts of said inorganic power and the polyhydric alcohols preferably makes up at least 50% of the total mass of the adhesive layer.

Description

Water-containing patch

The present invention relates to a water-containing patch containing a drug.

Conventionally, a drug is transdermally absorbed with a water-containing patch for the purpose of sustained release of the drug or local supply. For example, lidocaine is known to be capable of functioning as a pain relief agent for persistent pain such as herpes zoster or postherpetic neuralgia, a local anesthetic, etc. In addition, since it is particularly important to deliver a drug to a locally affected area, absorption by a transdermal route is more appropriate than an administration route such as oral or injection, and a patch is attracting attention (Patent Document 1).

JP-A-4-305523

However, even if the initial adhesiveness is appropriate, the conventional adhesive has a great deal of pain when peeled off from the skin after use because the adhesive strength becomes too strong with time after application to the skin. In particular, for patients suffering from persistent pain such as herpes zoster or postherpetic neuralgia, pain when peeling the patch is a very important problem.

Also, the patch needs to be applied to the affected area for a long time, especially in the case of persistent pain such as herpes zoster or postherpetic neuralgia, because it is often applied to frequently moving places such as joints, The movement may cause a part of the patch to peel off. However, the conventional patch has a problem that it is difficult to re-stick to the skin in such a case.

The present invention has been made in view of the above circumstances, and provides a water-containing patch that contains a drug such as lidocaine, reduces the pain given to the user at the time of peeling, and has excellent re-sticking power. With the goal.

The inventor suppresses the blending amount of water to 30% by mass or less with respect to the total mass of the pressure-sensitive adhesive layer, and adds 40% by mass or more of polyhydric alcohol to the total mass of the pressure-sensitive adhesive layer. It was found that the re-sticking force was improved while the increase in the adhesive force was moderately suppressed by blending into the present invention, and the present invention was completed. Specifically, the present invention provides the following.

(1) A hydrous patch comprising a support and a pressure-sensitive adhesive layer located on the support,
In the pressure-sensitive adhesive layer, a drug, water in an amount of 30% by mass or less with respect to the total mass of the pressure-sensitive adhesive layer, and a polyhydric alcohol in an amount of 40% by mass or more with respect to the total mass of the pressure-sensitive adhesive layer; A water-containing patch comprising

(2) The water-containing patch according to (1), wherein the polyhydric alcohol contains glycerin.

(3) Further containing inorganic powder, and the sum of the blending amount of the inorganic powder and the polyhydric alcohol is 50% by mass or more based on the total mass of the pressure-sensitive adhesive layer (1) or (2) The hydrous patch as described.

(4) The water-containing patch according to any one of (1) to (3), wherein the drug contains lidocaine and / or a pharmacologically acceptable salt thereof.

(5) The water-containing patch according to any one of (1) to (4), which is used for treatment or prevention of shingles or postherpetic neuralgia.

According to the present invention, the pressure-sensitive adhesive layer includes water in an amount of 30% by mass or less with respect to the total mass of the pressure-sensitive adhesive layer, and polyhydric alcohol in an amount of 40% by mass or more with respect to the total mass of the pressure-sensitive adhesive layer. Therefore, the resticking force can be improved while suppressing an increase in adhesive strength so that the pain given to the user at the time of peeling is reduced.

Hereinafter, embodiments of the present invention will be described, but the present invention is not intended to be limited.

The hydrous patch according to the present invention comprises a support and an adhesive layer located on the support and containing a drug. Details of each element will be described below.

[Adhesive layer]
In the water-containing patch of the present invention, the pressure-sensitive adhesive layer has water in an amount of 30% by mass or less with respect to the total mass of the pressure-sensitive adhesive layer and a polyvalent amount in an amount of 40% by mass or more with respect to the total mass of the pressure-sensitive adhesive layer. And alcohol. Thereby, the re-sticking force can be improved while suppressing an increase in adhesive force.

The amount of water may be appropriately selected from the range of 30% by mass or less, more preferably 28% by mass or less, as long as it is acceptable in the production of the preparation. If the lower limit of the amount of water is too small, the amount of other components (for example, glycerin and the like) increases, and the manufacturing cost increases, and a sufficient amount of other components (for example, polyacrylic acid and / or its components). In view of the fact that the salt is not dissolved, it may be appropriately set. In general, it is preferably 10% by mass, more preferably 15% by mass with respect to the total mass of the pressure-sensitive adhesive layer.

The blending amount of the polyhydric alcohol may be appropriately selected from the above range, but it is 40 masses with respect to the total mass of the pressure-sensitive adhesive layer from the viewpoint of further suppressing the increase in the adhesive force and improving the excellent re-adhesion force. % Or more, and more preferably 50% by mass or more. In addition, the upper limit of the blending amount of the polyhydric alcohol may be appropriately set in consideration of the blending amount of water, manufacturing cost, ease of bleeding, and the like.

Examples of the polyhydric alcohol include glycerin, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, 1,3-butylene glycol, 1,3-propanediol, 1,3-butanediol, 1,4-butanediol, Examples include 1,2,6-hexanetriol, maltitol, and xylitol. These may be used alone or in combination of two or more, and among them, glycerin is preferably contained. The glycerin includes concentrated glycerin (glycerin content: 98.0 to 101.0%) and other glycerin (glycerin content: 84 to 87%), and is not particularly limited. 101.0%) is more preferable.

The drug is not particularly limited and may be any drug. However, the topical anesthetics and various kinds of drugs are particularly suitable for use in the treatment or prevention of neuralgia because the hydrous patch of the present invention is particularly required. Analgesics. Specifically, local anesthetics such as tetracaine, procaine, dibucaine, lidocaine, benzocaine, mexiletine, ropivacaine, and pharmaceutically acceptable salts thereof, indomethacin, ketoprofen, piroxicam, felbinac, bufexamac, suprofen, flurubi Non-steroidal anti-inflammatory drugs such as profen, diclofenac, ibuprofen, loxoprofen, ampenac and their pharmaceutically acceptable salts, antidepressants such as amitriptin, anticonvulsants such as gabapentin, steroids such as prednisolone, capsaicin, Other analgesics such as acetaminophen, aspirin, codeine phosphate, amitriptin, naproxen, phenacetin, vaccinia virus inoculated rabbit inflammation skin extract and the like. Among these, a local anesthetic is preferable, and lidocaine and / or a pharmacologically acceptable salt thereof is more preferable. Lidocaine is a useful drug as listed in the Japanese Pharmacopoeia as a relief agent for persistent pain such as herpes zoster or postherpetic neuralgia, a local anesthetic, and an antiarrhythmic drug.

Lidocaine contained in the pressure-sensitive adhesive layer is mainly in a free form, but may be in the form of a pharmacologically acceptable salt. The pharmacologically acceptable salt is not particularly limited, but is preferably a hydrochloride.

The compounding amount of lidocaine and / or a pharmacologically acceptable salt thereof (hereinafter also referred to as lidocaine) is not particularly limited, but if it is too much, lidocaine precipitates vigorously and is difficult to maintain in the preparation. On the other hand, if the amount is too small, it is difficult to obtain a sufficient effect. Therefore, the amount of lidocaine is 0.1 to 50% by weight, preferably 1.0 to 30% by weight, more preferably 3 to 10% by weight, based on the total weight of the pressure-sensitive adhesive layer. Most preferably, it is 5 mass%.

In addition to the above-mentioned components, the pressure-sensitive adhesive layer is made of an inorganic powder, a surfactant, an excipient such as N-methyl-2-pyrrolidone, polyacrylic acid and / or a salt thereof, a cross-linking agent, a cross-linking agent, if necessary. It may contain optional components such as a control agent, an adhesion enhancer, a lidocaine dissolution aid, a pH adjuster, a cooling agent, a water-soluble polymer compound, an inorganic powder, an antioxidant, a preservative, and a pigment.

Examples of the inorganic powder include kaolin, zinc oxide, titanium oxide, anhydrous silicic acid, light anhydrous silicic acid and the like, and these may be included singly or in combination of two or more. Inorganic powder suppresses an excessive increase in adhesive strength. Therefore, the blending amount of the inorganic powder is preferably such that the sum of the blending amount of the polyhydric alcohol is 50% by mass or more with respect to the total mass of the pressure-sensitive adhesive layer.

One of the advantages of the water-containing patch according to the present invention is that the adhesive layer contains the predetermined amount of water and a polyhydric alcohol, thereby exhibiting effects such as suppression of increase in adhesive force. For example, it may contain a surfactant or the like, but even if it does not contain it, the water-containing patch has excellent suppression of an increase in adhesive force.

The surfactant is not particularly limited,
Sorbitan fatty acid esters such as sorbitan sesquioleate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, glyceryl fatty acid esters such as glyceryl monostearate, polyglycerin fatty acid esters such as hexaglyceryl monolaurate, decaglyceryl dekaoleate, Polyethylene glycol fatty acid esters such as polyethylene glycol distearate, polyethylene glycol monostearate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitol tetraoleate Polyoxyethylene sorbite fatty acid ester, monooleic acid polyoxy Polyoxyethylene glyceryl fatty acid esters such as ethylene glyceryl, polyoxyethylene alkyl ethers such as polyoxyethylene lauryl ether and polyoxyethylene cetyl ether, polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene decyl tetradecyl ether Surfactants such as polyoxyethylene fatty acid amides such as polyoxyethylene polyoxypropylene alkyl ether and polyoxyethylene stearamide, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, and the like. You may contain individually or in combination of 2 or more types. Although not particularly limited, polyoxyethylene sorbitan fatty acid esters are preferable, and polyoxyethylene sorbitan trioleate and polyoxyethylene sorbitan monooleate (polysorbate 80) are preferable.

The pH of the pressure-sensitive adhesive layer is preferably adjusted to 4.5 to 9, more preferably 6 to 7.4. If it is less than 4.5, the transfer of a drug, particularly lidocaine, to the skin is deteriorated. Therefore, the pH of the pressure-sensitive adhesive layer is desired to be 4.5 or more, but in such a weakly acidic pH range, it is different from a commonly used crosslinking agent, specifically dihydroxyaluminum aminoacetate (also known as Aluminum glycinate) is preferably used. Aluminum of dihydroxyaluminum aminoacetate elutes well from weak acidity to near neutrality, and can cross-link well with polyacrylic acid (salt) and the like described later.

The cross-linking agent is not limited to dihydroxyaluminum aminoacetate, and examples thereof include polyvalent metal salts. Among them, aluminum compounds are preferable. Examples of the aluminum compound include hydroxides such as dihydroxyaluminum aminoacetate, aluminum hydroxide, and aluminum hydroxide gel described above, or salts of inorganic or organic acids such as aluminum chloride, aluminum sulfate, aluminum acetate, and aluminum stearate. And double salts such as aluminum alum, aluminates such as sodium aluminate, inorganic aluminum complex salts, and organic aluminum chelate compounds. These aluminum compounds may be water-soluble or sparingly soluble.

The pH can be set using a pH adjuster, such as tartaric acid, phosphoric acid, malic acid, citric acid, hydrochloric acid, sodium hydroxide, triethanolamine, diethanolamine, diisopropanolamine, etc. These may be included singly or in combination of two or more, but tartaric acid and phosphoric acid are preferred.

Examples of polyacrylic acid and / or salts thereof include polyacrylic acid, sodium polyacrylate, and partially neutralized polyacrylic acid “NP-800 (trade name)” and “NP-700 (trade name)” (Showa Denko) These may be included singly or in combination of two or more.

Examples of the adhesion enhancer include methacrylic acid / n-butyl acrylate copolymer, methyl acrylate / 2-ethylhexyl acrylate copolymer, polybutene, ester gum, terpene resin, alicyclic saturated hydrocarbon resin, and the like. . The blending amount thereof may be 1% by mass or more and 30% by mass or less, and preferably 5% by mass or more and 20% by mass or less, based on the total mass of the pressure-sensitive adhesive layer.

Examples of the crosslinking control agent include sodium edetate (disodium ethylenediaminetetraacetate), citric acid and the like, and these may be used alone or in combination of two or more, but sodium edetate is preferred.

Drugs, particularly lidocaine solubilizers include crotamiton, N-methyl-2-pyrrolidone, mint oil, 1,3-butylene glycol, etc., and these may be used alone or in combination of two or more. It's okay.

Examples of the refreshing agent include camphor and thymol, l-menthol, dl-menthol, 2-methyl-3- (l-menthyloxy) propane-1,2-diol, 3-l-mentoxypropane-1, Examples include menthol derivatives such as 2-diol and 5-methyl-2- (l-methylethyl) -cyclohexyl-2-hydroxypropionate, and these may be included singly or in combination of two or more. .

Examples of water-soluble polymer compounds include gelatin, agar, polyvinyl alcohol, polyvinyl pyrrolidone, propylene carbonate, carboxymethyl cellulose, carboxymethyl cellulose sodium, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, sodium alginate, maleic anhydride copolymer. , Carrageenan and the like, and these may be included singly or in combination of two or more.

Examples of the antioxidant include tocopherol acetate, ascorbic acid and / or derivatives thereof, sodium sulfite, sodium hydrogen sulfite, sodium pyrosulfite, sodium nitrite, dibutylhydroxytoluene and the like. These may be used alone or in combination of two or more. May be included in combination.

Examples of the preservative include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, thymol, and the like, and these may be used alone or in combination of two or more.

The type of the dye is not particularly limited, and examples thereof include dyes described in the Legal Dye Handbook, and these can be used alone or in combination of two or more.

[Support]
The support may be composed of fabrics such as woven fabrics, nonwoven fabrics, and knitted fabrics that are conventionally used for patches, resin films, paper, and laminates thereof. The material of the support may be one or more selected from the group consisting of polypropylene, polyethylene, polybutylene, polyethylene terephthalate, rayon, cotton, and polyurethane, and is not particularly limited, but is preferably polyethylene terephthalate. From the viewpoint of cost, a support composed of a nonwoven fabric made of polyethylene terephthalate is preferably used. In addition, when using a resin film, it is possible to use a support that has been printed or kneaded with white, skin color, or colored or filled with characters, etc., improving the anchoring property of the adhesive. In order to achieve this, it is also possible to use a support that has been subjected to polyurethane treatment, matting treatment, or the like.

[Peeling liner]
The patch according to the present invention may further include a release liner that covers the pressure-sensitive adhesive layer. As such a release liner, a resin film such as polyethylene terephthalate or polypropylene is preferable, and a release film such as silicon or an embossed film may be used. Moreover, what printed or kneaded paints, such as white, can also be used as a peeling liner.

The above patches can be used for any purpose depending mainly on the drug to be blended. However, particularly useful uses include the treatment or prevention of persistent pain such as herpes zoster or postherpetic neuralgia. Since the patch of the present invention suppresses an increase in adhesive force, the pain given to the user at the time of peeling is reduced, and the adhesive is kept applied for a long time, and has an excellent re-adhesion power. Re-sticking can be performed.

(Preparation method)
The patch of the present invention can be prepared by a conventional method, and the above-mentioned essential components and, if necessary, the above optional components are appropriately blended and kneaded until uniform by a known method. After spreading on the release liner so that the pressure-sensitive adhesive mass at 0.03 to 0.15 g / cm ² , a support was further laminated on the surface of the pressure-sensitive adhesive layer, and then cut into a 100 mm × 140 mm rectangular shape Can be prepared. It can also be prepared by first spreading a pressure-sensitive adhesive on a support and then laminating a release liner thereon.

Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not limited to an Example.

<Examples 1 to 11 and Comparative Examples 1 to 3>
For Examples and Comparative Examples, the components shown in Tables 1 to 3 were stirred and mixed for a certain period of time, and then the adhesive mass per patch (140 mm × 100 mm) was about 14 g on the release liner. It was spread evenly. Thereafter, a nonwoven fabric made of polyethylene terephthalate was bonded to the surface of the pressure-sensitive adhesive layer, and then cut into a size of 100 mm × 140 mm to prepare a patch. The amounts shown in Tables 1 to 3 are all mass%.

(Test Example 1) Adhesiveness to skin The patches of each Example and Comparative Example were cut into 2.0 × 3.0 cm and attached to the human forearm. After 8 hours, using "Sun Rheo Meter CR-200D" (manufactured by Sun Scientific Co, Ltd.), the patch was applied to the skin at a speed of 300 mm / min according to the test method of JIS Z0237. The peel force when peeled in the direction was measured.

As shown in Tables 1 to 3, Examples 1 to 11 had lower adhesive strength than Comparative Examples 1 to 3, while having necessary adhesive strength of 41.5 g / 2.5 cm or more. In fact, none of the patches of Examples 1 to 11 were naturally peeled off from the skin during the application for 8 hours.

(Test Example 2) Pain at the time of peeling In Test Example 1, the degree of pain at the time of peeling from the human forearm after 8 hours was subjected to sensory evaluation by eight monitors. The evaluation criteria are as follows.
A: There is no pain at all.
○: I do not feel pain.
Δ: Somewhat strong pain is felt, and the skin is pulled.
X: A strong pain is felt and accompanied by pain.

As shown in Tables 1 to 3, in Examples 1 to 11, the pain during peeling was highly reduced compared to Comparative Examples 1 to 3. In particular, in Examples 1 to 5 and 7 to 11, no pain at the time of peeling was felt.

(Test Example 3) Re-sticking power to the skin The patch after 8 hours had been peeled off from the skin and then applied to the skin again. Thereafter, the peel force was measured in the same procedure as in Test Example 1.

As shown in Tables 1 to 3, in Examples 1 to 11, the adhesive strength after re-adhesion was higher than in Comparative Examples 1 to 3, and had excellent re-adhesion power.

<Examples 12 to 13>
A patch was prepared in the same procedure as in Example 1 except that each component shown in Table 4 was blended.

Test Example 4 Lidocaine Skin Permeability 0.05 mol / L McIlvaine buffer (pH 7.4) is 1 in the receiver on the dermis layer side of hairless mouse-extracted skin (purchased from Japan SLC) set in a vertical diffusion cell. 2 mL was put, and 1.77 cm ² pieces of the adhesive layer of each patch were attached to the donor on the stratum corneum side. Thereafter, 0.6 mL of the receiver solution was collected every predetermined time over 24 hours, and the lidocaine concentration in the receiver solution was measured by the HPLC method. After 0.6 mL was collected, the receiver was supplemented with 0.6 mL of a new 0.05 mol / L McIlvaine buffer. Table 5 shows the cumulative amount of lidocaine permeated for 24 hours, which is the sum of the concentrations of lidocaine measured at each time point.

As shown in Table 5, in Examples 12 to 13, the transdermal absorbability of lidocaine equivalent to or higher than that of Comparative Example 3 was obtained. Thereby, it was confirmed that the percutaneous absorbability of the drug is improved in addition to the above-described suppression of increase in adhesive force and re-sticking force.

Claims

A water-containing patch comprising a support and an adhesive layer located on the support,
In the pressure-sensitive adhesive layer, a drug, water in an amount of 30% by mass or less with respect to the total mass of the pressure-sensitive adhesive layer, and a polyhydric alcohol in an amount of 40% by mass or more with respect to the total mass of the pressure-sensitive adhesive layer; A water-containing patch comprising
The water-containing patch according to claim 1, wherein the polyhydric alcohol contains glycerin.
The water-containing patch according to claim 1 or 2, further comprising an inorganic powder, wherein the sum of the blending amount of the inorganic powder and the polyhydric alcohol is 50% by mass or more based on the total mass of the pressure-sensitive adhesive layer. .
The water-containing patch according to any one of claims 1 to 3, wherein the drug contains lidocaine and / or a pharmacologically acceptable salt thereof.
The water-containing patch according to any one of claims 1 to 4, which is used for treatment or prevention of herpes zoster or postherpetic neuralgia.