JP4799874B2 - Patch - Google Patents

Description

  The present invention relates to a patch. More specifically, the present invention relates to a patch containing a rubber adhesive, a tackifier, and a liquid additive in a plaster layer.

  Conventionally, rubber-based elastomers have been used as adhesives for patches because of their excellent low-temperature properties. However, when rubber-based elastomers are used, rubber systems with different average molecular weights are used to adjust cohesion and adhesion. Elastomers are mixed and used, and tackifiers such as tackifying resins and low molecular weight polybutenes are blended to provide tackiness. For the rubber-based elastomer pressure-sensitive adhesive, a plaster composition having desirable physical properties is adopted by examining the molecular weight of the rubber-based elastomer, the blending ratio of the rubber-based elastomers having different molecular weights, the blending ratio of the tackifier, and the like.

  Generally, in a percutaneous absorption preparation for the purpose of percutaneous absorption, for example, a liquid additive may be further added to the plaster for the purpose of promoting absorption or improving drug solubility. When liquid additives are added, the fluidity of the pressure-sensitive adhesive increases with the amount of the liquid additive, so the cold flow and cohesive strength of the plaster are often reduced during the storage period, resulting in extreme handling. May fall. For patches using rubber-based elastomers, if the molecular weight of the polymer rubber-based elastomer is set high for the purpose of solving this problem, the cold flow and cohesive strength are suppressed, but the skin adhesion is significantly reduced. In some cases, omission may occur during pasting. Therefore, when a liquid additive is blended, particularly when the blending amount is large, it is extremely difficult to design a plaster that balances cold flow suppression, cohesion and adhesiveness.

As means for suppressing these cold flows, for example, many methods for blending fillers have been proposed. As one of them, organic or inorganic fibrous or non-fibrous materials are used for the purpose of dissolving a large amount of drug in a non-acrylic adhesive layer having a glass transition temperature of −71 ° C. or less and improving adhesive strength and cohesive strength. Has been proposed (for example, see Patent Document 1). However, since the filler used for improving the cohesiveness is a solid insoluble in a solvent, it is extremely difficult to uniformly hold the filler in the coating liquid during coating.
Japanese Patent Laid-Open No. 3-127727

  In view of the above circumstances, the problem to be solved by the present invention is to use a rubber-based pressure-sensitive adhesive as a pressure-sensitive adhesive, and even when a relatively large amount of liquid additive is blended, it is solid-filled to suppress cold flow. It is an object of the present invention to provide a patch having a plaster layer excellent in the balance of cold flow suppression, cohesiveness and adhesiveness, without the need for blending an agent.

  As a result of intensive studies to solve the above problems, the present inventors compound a small amount of a styrene-based thermoplastic elastomer, which is a solvent-soluble component, even when a liquid additive is blended with a rubber-based adhesive. As a result, it was found that cold flow and cohesive force, which are practically problematic, can be suppressed and the skin adhesiveness is not impaired, and the present invention has been completed. That is, the present invention is as follows.

[1] A patch having a paste layer on at least one side of the support layer, the paste layer containing a rubber-based adhesive, a tackifier, a liquid additive, and a styrene-based thermoplastic elastomer. A patch, characterized by
[2] The patch according to the above [1], wherein the paste layer contains 5 to 35% by weight of a liquid additive.
[3] The liquid additive is a fatty acid alkyl ester composed of a saturated or unsaturated higher fatty acid having 12 to 16 carbon atoms and a lower monohydric alcohol having 1 to 4 carbon atoms, and a long-chain branched alcohol having 16 to 22 carbon atoms. The patch of the above-mentioned [2], which is one or more selected.
[4] The patch according to any one of [1] to [3], wherein the plaster layer contains 0.3 to 5% by weight of a styrene thermoplastic elastomer as the amount of styrene units.
[5] The patch according to [4], wherein the styrenic thermoplastic elastomer is at least one selected from styrene / isoprene / styrene block copolymer, styrene / butadiene / styrene block copolymer, and styrene / ethylene / butylene / styrene block copolymer. Agent.
[6] The rubber-based elastomer is selected from polyisobutylene, polyisoprene, and butyl rubber, and is selected from a high-molecular-weight rubber-based elastomer having a viscosity average molecular weight of 600,000 to 1550,000, and polyisobutylene, polyisoprene, and butyl rubber. Is a mixture of a medium molecular weight rubber elastomer having a molecular weight of 40,000 to 85,000, and the mixing ratio of the high molecular weight rubber elastomer and the medium molecular weight rubber elastomer is 1: 1 to 1: 2 by weight. The patch according to any one of the above [1] to [5].
[7] The tackifier is at least one selected from polybutene or polyisoprene having a number average molecular weight of 900 to 2900 and an alicyclic saturated hydrocarbon resin having a softening point of 70 to 140 ° C., and the amount of the tackifier is The patch according to any one of the above [1] to [6], which is 25 to 100% by weight based on the rubber elastomer.
[8] The patch according to any one of [1] to [7], further containing a transdermally absorbable drug.

  ADVANTAGE OF THE INVENTION According to this invention, the increase in the fluidity | liquidity of the adhesive by the addition of a liquid component can be suppressed, and the patch which was excellent in suppression of cold flow, cohesiveness, and adhesiveness can be provided. In particular, even when a large amount of a liquid additive is blended in a plaster made of a rubber-based elastomer, it provides a patch that suppresses cold flow and cohesion, which are problematic, and has sufficient skin adhesiveness. be able to. Therefore, the present invention is particularly suitable for a transdermally absorbable preparation often containing a liquid additive.

  The present invention is a patch having a plaster layer on at least one side of a support layer, and the plaster layer contains a rubber-based adhesive, a tackifier, a liquid additive, and a styrene-based thermoplastic elastomer. This is a patch.

  The rubber-based pressure-sensitive adhesive used in the present invention is not particularly limited as long as it is a rubber-based elastomer that can be used as a pressure-sensitive adhesive for patches, and the type thereof is one selected from polyisobutylene, polyisoprene, and butyl rubber or Two or more are preferred.

  The molecular weight of the rubber elastomer is not particularly limited as long as adhesive and cohesive force that can be used as a pressure-sensitive adhesive are imparted to the pressure-sensitive adhesive. However, a high molecular weight rubber elastomer and a medium molecular weight rubber-based elastomer can be used. A mixture of two types of rubber elastomer is preferable. The molecular weight of the high molecular weight rubber-based elastomer is preferably 600000 to 1550,000 in terms of viscosity average molecular weight, and more preferably 700000 to 1350,000. When the viscosity average molecular weight is less than 600,000, the fluidity of the paste cannot be sufficiently suppressed, a cold flow tends to be caused, and an internal cohesive force cannot be obtained. When the viscosity average molecular weight exceeds 1550000, the skin adhesive strength and tack of the plaster tend to decrease.

  The molecular weight of the medium molecular weight rubber-based elastomer is preferably 40,000 to 85,000, more preferably 45,000 to 65,000 in terms of viscosity average molecular weight. If the viscosity average molecular weight is less than 40,000, the sticky body may feel sticky, and the skin surface may be contaminated during and after the application, and if it exceeds 85,000, the adhesive strength and tack of the paste will tend to decrease. Indicates.

  The blending ratio of the high molecular weight rubber elastomer to the medium molecular weight rubber elastomer is preferably a weight ratio of high molecular weight rubber elastomer: medium molecular weight rubber elastomer = 1: 1 to 2: It is more preferable that it is 1.3-1.7.

  The type of the high molecular weight rubber-based elastomer may be one type or two or more types, and preferably one type. The kind of the medium molecular weight elastomer may be one kind or two kinds or more, preferably one kind. Further, the high molecular weight rubber elastomer and the medium molecular weight rubber elastomer may be the same or different, but are preferably the same.

The tackifier used in the present invention is not particularly limited, and can be selected from those known in the field of patches. From the viewpoint of obtaining a good tack, (i) a polybutene having a number average molecular weight of 900 to 2900, preferably 980 to 2000 (eg, 1-butene polymer, 2-butene polymer, 1-butene and 2-butene) Copolymer) or polyisoprene, and (ii) alicyclic saturated hydrocarbon resins having a softening point of 70 to 140 ° C, preferably 90 to 125 ° C. When the number average molecular weight of the polybutene or polyisoprene of (i) is less than 900, a sticky feeling is generated, and the skin surface may be contaminated during and after application. It is difficult to express the effect, and the tack tends to decrease. When the softening point of the alicyclic saturated hydrocarbon resin of (ii) is less than 70 ° C., a sticky feeling is generated, and there is a risk that the skin surface may be contaminated during and after application. The effect as a tackifier is difficult to be exhibited, and the tack tends to be lowered. The number average molecular weight here is a number average molecular weight measured by a gel permeation chromatography (GPC) method. The measurement conditions are eluent: tetrahydrofuran (THF), sample concentration (THF solution): 0.1% (W / V), column: GMH _XL + GMH _XL + G3000H _XL (manufactured by Tosoh Corporation, each 7.8 mmφ × 300 mm), column temperature: 40 ° C., detector: differential refractometer (RI), standard Sample: Polystyrene. The softening point is a value measured in accordance with the softening point measurement method of the pharmaceutical additive standard “alicyclic saturated hydrocarbon resin”.
A tackifier may be used alone or in combination of two or more.

  The amount of the tackifier is preferably 25 to 100% by weight, more preferably 30 to 50% by weight, based on the rubber-based pressure-sensitive adhesive. When the amount of the tackifier is less than 25% by weight, tack may be poor, and when it is more than 100% by weight, the cohesive strength of the paste may be remarkably reduced and a tendency to break may be exhibited.

  The styrenic thermoplastic elastomer used in the present invention refers to a thermoplastic elastomer having a polystyrene block unit in the molecule. The polystyrene block in the styrene-based thermoplastic elastomer molecule has a large steric hindrance with respect to the rubber-based elastomer, and restricts the fluidity of the rubber-based elastomer, thereby suppressing a decrease in cold flow and cohesive force. In addition, since the styrenic thermoplastic elastomer is dissolved in a solvent such as toluene or hexane, it can be uniformly dispersed in the coating liquid of the pressure-sensitive adhesive, and the uniform coating is possible.

The styrenic thermoplastic elastomer has a structure having polystyrene blocks at both molecular ends as represented by polystyrene block-medium phase block-polystyrene block, and the intermediate phase block is composed of rubber elastomer, tackifier and liquid additive. The copolymer is preferably a block that is compatible with any one or more of the agents. In general, polystyrene blocks and rubber-based elastomers are poorly compatible, causing phase separation and tending to localize polystyrene blocks. In such copolymers, the intermediate-phase block is a part of the rubber-based elastomer polymer. By stretching, the styrene blocks present at both ends are uniformly dispersed in the adhesive without being localized, so that the effect of restricting the fluidity of the rubber-based elastomer is enhanced.
Specific examples of the copolymer include SIS (styrene / isoprene / styrene block copolymer), SBS (styrene / butadiene / styrene block copolymer), SEBS (styrene / ethylene / butylene / styrene block copolymer), and the like. The weight ratio of polystyrene block / interphase block is preferably 10/90 to 30/70.
One or more styrenic thermoplastic elastomers can be used.

  The styrenic thermoplastic elastomer is preferably blended in the plaster layer in an amount of 0.3 to 5% by weight as the amount of styrene units (in other words, the amount of polystyrene block part), more preferably It mix | blends so that it may become a ratio of 0.6 to 4 weight%, Most preferably 0.7 to 3 weight%. If it exceeds 5% by weight, not only the fluidity of the rubber-based elastomer is suppressed more than necessary, but sufficient adhesion cannot be obtained, and the rubber-based elastomer and the styrene-based thermoplastic elastomer are easily phase separated. Tend. On the other hand, if it is less than 0.3% by weight, it is difficult to suppress a decrease in cold flow and cohesion to a level that does not cause a problem in practice.

The liquid additive used in the present invention is not particularly limited as long as it is compatible with the components constituting the rubber-based pressure-sensitive adhesive, and examples thereof include fatty acid alkyl esters and long-chain branched alcohols.
Examples of the fatty acid alkyl ester include fatty acid alkyl esters composed of a saturated or unsaturated higher fatty acid having 12 to 16 carbon atoms, preferably 12 to 14 carbon atoms, and a lower monohydric alcohol having 1 to 4 carbon atoms. Is a saturated fatty acid alkyl ester.
Examples of long-chain branched alcohols include long-chain branched alcohols having 16 to 22 carbon atoms, and specific examples include isostearyl alcohol and octyldodecanol.
The liquid additive is preferably blended in the plaster layer so as to be 5 to 35% by weight, particularly preferably 10 to 20% by weight. If it exceeds 35% by weight, not only the cold flow may not be sufficiently suppressed, but also the cohesive force is greatly reduced and cohesive failure tends to occur.

The support is not particularly limited, but polyester, nylon, saran, polyethylene, polypropylene, polyvinyl chloride, ethylene-ethyl acrylate copolymer, polytetrafluoroethylene, surlyn, metal from the viewpoints of handleability, flexibility, and anchoring properties A single film such as a foil or a laminated film of these can be used. In order to make the anchoring property better, a support in which a porous film is laminated on a single layer film made of the above material is more preferable. In this case, the plaster is preferably laminated on the porous film side.
Although there is no limitation in particular in the thickness of a support body, 1-50 micrometers is preferable and 1-30 micrometers is more preferable.

Moreover, in order to improve the anchoring property between the support and the adhesive layer, the support may be laminated with a nonwoven fabric or a woven fabric. The material of the nonwoven fabric or the woven fabric is not particularly limited, and can be appropriately selected from materials usually used in the field of patches. Examples of such a material include polyester, polypropylene, polyamide, and the like. The basis weight of the nonwoven fabric or woven fabric, usually 1 to 100 g / ^{m 2,} preferably for the reason that is a 6~50g / ^{m 2,} the adhesion feeling to the skin surface at the time of flexibility and sticking is good 6 ˜30 g / m ² is particularly preferred.

By containing a transdermally absorbable drug in the patch of the present invention, the patch of the present invention can be used as a transdermally absorbable preparation.
The percutaneously absorbable drug is not particularly limited as long as it has transdermal absorbability. Specifically, it is a general anesthetic, hypnotic / sedative, antidepressant, antipyretic analgesic / antiphlogistic, antipruritic, and neuropsychiatric. Drugs, local anesthetics, skeletal muscle relaxants, autonomic drugs, antispasmodics, antiparkinson drugs, antihistamines, cardiotonic drugs, arrhythmic drugs, diuretics, antihypertensive drugs, vasoconstrictors, coronary vasodilators, Peripheral vasodilators, arteriosclerotic drugs, cardiovascular drugs, respiratory stimulants, antitussive expectorants, hormonal drugs, topical suppurative drugs, analgesic / antipruritic / astringent / anti-inflammatory drugs, parasitic skin disease drugs, hemostasis Drugs, gout treatment drugs, diabetes drugs, antineoplastic drugs, antibiotics, chemotherapeutic drugs, narcotics and the like can be exemplified.

  The content of the transdermally absorbable drug is appropriately set depending on the type of drug, the purpose of administration, etc., but is usually 0.5 to 60% by weight, preferably 1 to 30% by weight of the drug in the plaster layer. Contain. When the content is less than 0.5% by weight, it is difficult to absorb a sufficient amount of drug to exert a pharmacological effect, and when it exceeds 60% by weight, the skin adhesiveness is lowered.

  In addition, the patch of the present application is used to remove the adhesive layer from the release liner before use such as during manufacture, transportation or storage, in order to prevent adhesion to other than the object of use or to prevent deterioration of the adhesive. It is preferable to cover and protect with.

  The release liner is not particularly limited, and a known release liner can be used. Specifically, a release treatment agent layer comprising a release treatment agent is a release liner substrate (for example, paper such as Japanese paper, western paper, glassine paper; a substrate made of a fibrous material such as a nonwoven fabric or cloth; a polyester film, etc. Release film formed on the surface of plastic film, metal vapor-deposited plastic film, etc.), plastic film with high peelability itself [eg, polyethylene film (linear low density polyethylene film, etc.), ethylene-α-olefin copolymer Polyolefin resin film such as coalesced film; Teflon (registered trademark) film] release liner, and material of the plastic film having high peelability (for example, polyolefin resin such as polyethylene, ethylene-α-olefin copolymer) , Teflon (registered trademark), etc.) For example, a release liner obtained by laminating or coating a metal foil, a plastic film, or the like) can be used. The release surface of the release liner may be made of a release treatment agent, or may be made of a plastic film material having high peelability.

The release treatment agent is not particularly limited, and examples thereof include release agents such as a long-chain alkyl group-containing polymer, a silicone polymer (silicone release agent), and a fluorine polymer (fluorine release agent). These release treatment agents can be used alone or in combination. In addition, when both surfaces of the release liner are formed of a release treatment agent, the release treatment agents for forming both release surfaces may be the same or different.
The thickness of the release liner is not particularly limited, but is preferably 25 to 1000 μm, and more preferably 50 to 250 μm.

The method for producing the patch of the present invention is not particularly limited. For example, a rubber adhesive, a tackifier, a liquid additive, a styrene thermoplastic elastomer, and if necessary, a drug is dissolved in an appropriate solvent such as toluene or hexane. And the obtained solution is applied on a support and dried.
It can also be produced by applying the above solution on a release liner and drying to form a paste layer on the release liner and then bonding the support to the paste layer.

  The thickness of the plaster layer is preferably 20 to 250 μm, and more preferably 50 to 200 μm.

  Hereinafter, the patch of the present invention will be described in more detail with reference to Examples and Test Examples. Needless to say, various applications can be made without departing from the technical idea of the present invention.

[Example 1-15]
10 parts of high molecular weight polyisobutylene (Opanol B-80, viscosity average molecular weight 820000, manufactured by BASF), 15 parts of medium molecular weight polyisobutylene (Opanol B-12, viscosity average molecular weight 55000, manufactured by BASF), and polybutene as tackifier ( 10 parts of Nisseki Polybutene HV-300, number average molecular weight 1,400, manufactured by Nippon Petrochemical Co., Ltd.) was dissolved in toluene to prepare a rubber polymer solution. To this solution, isopropyl myristate (IPM-100, manufactured by NIKKO Chemical) and a styrenic thermoplastic elastomer as liquid additives and the blending amounts shown in Table 1 (% by weight in the plaster layer after drying) and Thus, a coating solution having a solute concentration of 30% was obtained. This liquid was applied to a polyethylene terephthalate (PET) liner that had been subjected to silicone release treatment so that the thickness of the paste layer after drying was 150 μm, and dried at 100 ° C. for 3 minutes in a hot air circulating dryer. A body layer was obtained. On this plaster layer, a support (product number 1109, manufactured by 3M) was laminated to obtain a patch.

[Comparative Example 1]
A patch was obtained in the same manner as in Example 1 except that styrene-based thermoplastic elastomer was not blended with Example 1.

[Comparative Example 2]
A patch as in Example 1 except that the high molecular weight polyisobutylene is changed to a polyisobutylene having a different viscosity average molecular weight (Opanol B-150, average molecular weight 2600000, manufactured by BASF), and no styrenic thermoplastic elastomer is added. Got.

Test Example 1 Cold Flow Evaluation A sample obtained by molding the patches of Examples 1 to 15 and Comparative Examples 1 and ² into a 5 cm ² square was folded into a 3 cm × 6 cm separator so that the release surface was inside. Scissors were sealed with a 4 cm × 4 cm Hytron / aluminum wrapping material. Put these preparations in a 25 ° C incubator, and after 1 month, take out the separator from the packaging material. If there is a cold flow, use a peaked loupe with a scale. The shortest distance until was read.
Judgment criteria (1-5 points)
1 point: Cold flow occurred, and the shortest distance from the edge to the protruding tip of the plaster exceeded 3 mm.
2 points: Cold flow occurred, and the shortest distance from the edge to the protruding tip of the plaster was 1 to 3 mm.
3 points: Cold flow occurred, and the shortest distance from the edge to the protruding tip of the plaster was 0.5 to 1 mm.
4 points: Cold flow occurred, and the shortest distance from the edge to the protruding tip of the plaster was less than 0.5 mm.
5 points: No cold flow occurred.

Test Example 2 Evaluation of Adhesive Strength The patches of Examples 1 to 15 and Comparative Examples 1 and 2 were cut into a width of 12 mm, and the adhesive strength was determined according to the JIS adhesive tape / adhesive sheet test method 90 degree peeling method (JISZ0237). It was measured.

Test Example 3 Evaluation of Holding Power The patches of Examples 1 to 15 and Comparative Examples 1 and 2 cut to a width of 10 mm and a length of 20 mm were affixed to a bakelite plate, and a roller having a load of 850 g was reciprocated to be brought into close contact. The bakelite plate was hung in a 40 ° C atmosphere so as to be perpendicular to the ground, and a 150 g load was attached to the end (lower part) of the patch that was left for 30 minutes, and the time until the patch spontaneously dropped was measured. .

・表中の各記号は以下を表す。また、％は、膏体層中に占める重量％を表す。
ＳＩＳ １ スチレン／中間相ゴム＝１５／８５ （Ｑｕｉｎｔａｃ３５２０、日本ゼオン製）
ＳＩＳ ２ スチレン／中間相ゴム＝２５／７５ （Ｑｕｉｎｔａｃ３４６０、日本ゼオン製）
ＳＥＢＲ スチレン／中間相ゴム＝１４／８６ （クレイトンＧ１６５７、クレイトンポリマージャパン製）
・表中の接着力の単位はＮ／１２ｍｍ幅、保持力の単位は分である。
・表中のスチレン含率は、膏体層中に占めるスチレン系熱可塑性エラストマー中のスチレン単位の重量％を示したものである。

・ Each symbol in the table represents the following. Moreover,% represents the weight% which occupies in a paste layer.
SIS 1 Styrene / Intermediate phase rubber = 15/85 (Quintac 3520, manufactured by Nippon Zeon)
SIS 2 Styrene / Interphase rubber = 25/75 (Quintac 3460, manufactured by Nippon Zeon)
SEBR styrene / intermediate phase rubber = 14/86 (Clayton G1657, manufactured by Kraton Polymer Japan)
In the table, the unit of adhesive force is N / 12 mm width, and the unit of holding force is minutes.
-The styrene content in a table | surface shows the weight% of the styrene unit in the styrene-type thermoplastic elastomer which occupies in a paste layer.

  The patch of the present invention has a good balance of cold flow suppression, cohesiveness, and adhesiveness, and each satisfies the practical level, and thus can be used for a general patch application. The patch of the present invention can be used as a transdermally absorbable preparation by containing a transdermally absorbable drug.

Claims (7)

A patch having a plaster layer on at least one surface side of the support layer, the plaster layer is a rubber-based adhesive, Ri Na contain tackifier, liquid additive and styrene-based thermoplastic elastomer,
The rubber-based pressure-sensitive adhesive is selected from polyisobutylene, polyisoprene and butyl rubber, and is selected from a high molecular weight rubber elastomer having a viscosity average molecular weight of 600,000 to 1550,000, and polyisobutylene, polyisoprene and butyl rubber, and a viscosity average molecular weight of 40,000. It is a mixture of a medium molecular weight rubber-based elastomer having a molecular weight of ˜85000, and the mixing ratio of the high molecular weight rubber-based elastomer to the medium molecular weight rubber-based elastomer is 1: 1 to 1: 2. A patch, characterized by   The patch according to claim 1, wherein the plaster layer contains 5 to 35% by weight of a liquid additive.   1 wherein the liquid additive is selected from a fatty acid alkyl ester composed of a saturated or unsaturated higher fatty acid having 12 to 16 carbon atoms and a lower monohydric alcohol having 1 to 4 carbon atoms, and a long chain branched alcohol having 16 to 22 carbon atoms. The patch according to claim 2, wherein the patch is at least one species.   The patch according to any one of claims 1 to 3, wherein the plaster layer contains 0.3 to 5 wt% of a styrene-based thermoplastic elastomer as an amount of styrene units.   The patch according to claim 4, wherein the styrenic thermoplastic elastomer is at least one selected from styrene / isoprene / styrene block copolymer, styrene / butadiene / styrene block copolymer and styrene / ethylene / butylene / styrene block copolymer. The tackifier is at least one selected from polybutene or polyisoprene having a number average molecular weight of 900 to 2900 and an alicyclic saturated hydrocarbon resin having a softening point of 70 to 140 ° C., and the amount of the tackifier is a rubber-based adhesive. patch according to any one of claims 1 to 5 which is 25 to 100 wt% based agent. The patch according to any one of claims 1 to 6 , further comprising a transdermal drug.