WO2023210689A1

WO2023210689A1 - Adhesive patch

Info

Publication number: WO2023210689A1
Application number: PCT/JP2023/016450
Authority: WO
Inventors: 昇辰巳; 英利濱本; 賢樹石橋
Original assignee: 株式会社メドレックス
Priority date: 2022-04-27
Filing date: 2023-04-26
Publication date: 2023-11-02

Abstract

The present invention provides an adhesive patch which comprises a support and a plaster disposed on one surface of the support and which has a good balance among three properties, i.e., excellent tack, excellent shear resistance, and excellent peel adhesion. The plaster comprises (i) an oil which is liquid at room temperature, the amount of which is 20 wt% or larger with respect to the overall weight of the plaster, (ii) a rubber-based polymer, the amount of which is 5-20 wt% with respect to the overall weight of the plaster, and (iii) a terpene resin, the content of the terpene resin being up to 2.3 times the content of the rubber-based polymer.

Description

patch

The present invention relates to a patch, and more particularly to a matrix-type patch containing an oil that is liquid at room temperature as an active ingredient.

Matrix-type patches, which include an adhesive, such as a support and a paste containing a drug and adhesive composition, have three basic properties: tack, share resistance, and peel adhesion. It is required to maintain a balance of characteristics. Tack is a property that immediately sticks to the skin when applied and exhibits the minimum necessary adhesive strength, and is also called instantaneous adhesive strength. If the tack is insufficient, it will not adhere well to the skin, and the medicinal component will not be able to sufficiently penetrate the skin. Cohesive force is a property necessary for the adhesive to maintain its shape without flowing, and if the cohesive force is insufficient, the plaster will be destroyed when peeled off and remain on the skin. Adhesive force is the force resisted when peeled from the skin, and is a property that is a measure of the strength of adhesion. If the adhesive strength is within an appropriate range, the patch can be left on the skin for a long time and can be easily removed, but if the adhesive strength is too strong, there will be a lot of resistance when it is removed from the skin, causing pain. The feeling of use worsens.
Generally, tack and adhesive strength and cohesive strength have a contradictory relationship, so it has been difficult to achieve an excellent balance of these three properties. For example, improving the tack and adhesion of a patch reduces its cohesive strength, which causes the paste to remain on the skin when removed; There was a problem that the agent became difficult to stick to the skin.
Therefore, there is a need for a patch that has excellent tack, cohesive force, and adhesive strength properties, and which maintains a good balance of these properties.

In recent years, the physiological activity of various oils extracted from plants has attracted attention, and they are also included in pharmaceuticals and cosmetics used as external preparations. If a patch containing such an oil as an active ingredient could be prepared, the active ingredient could be administered in a sustained manner, and the effect could be sustained at a stable blood concentration, while side effects could be reduced. Very useful.

Patent Document 1 discloses a patch composition containing a drug, an organic solvent, a lipophilic paste base, and a powder. Patent Document 1 states that if only a lipophilic paste base is used, the main drug solution may form independent vacuoles and be difficult to be released from the paste; however, by adding powder, the voids between the powders and The main drug solution stored in the gap between the powder and the plaster gradually reaches the surface of the plaster through the gaps, improving the drug release properties and, as a result, improving the adhesiveness of the patch. It is stated that the drug's strength has been improved, and it has also become possible to improve transdermal absorption and sustained release.
Further, Patent Document 2 discloses a patch that can exhibit excellent tackiness to the skin when applied and has reduced peeling from the skin during application. In Patent Document 2, the adhesive patch includes a support, an acrylic adhesive, and a solid that is incompatible with the acrylic adhesive and is solid at 40°C. It is characterized by containing an adhesive layer containing a resin, a plasticizer, and a drug, and by using a combination of a solid resin and a plasticizer, the tack and cohesive force of the adhesive layer can be improved. It is stated that it is possible to achieve both.
However, no patch has been reported that contains a certain amount or more of oil that is liquid at room temperature and has excellent, well-balanced properties of tack, cohesive force, and adhesive force.

International Publication No. 2013/191187 International Publication No. 2016/121805

An object of the present invention is to provide a patch that contains a certain amount or more of an oil component that is liquid at room temperature and is excellent in the three properties of tack, cohesive force, and adhesive force in a well-balanced manner.

The present inventors investigated the formulation of a matrix-type patch containing 20% by weight or more of oil and found that a rubber-based polymer was used as the adhesive, and a terpene resin was blended in a predetermined ratio to the rubber-based polymer. The present inventors have discovered that it is possible to obtain a patch that is excellent in all of tack, cohesive force, and adhesive force, and in which these physical properties are maintained in a well-balanced manner, and the present invention has been completed.
That is, the present invention provides the following aspects.
[Item 1] A patch having a plaster provided on one side of a support, the plaster comprising:
(i) an oil content that is liquid at room temperature in an amount of 20% by weight or more based on the total weight of the plaster;
(ii) a rubber-based polymer in an amount of 5% to 20% by weight based on the total weight of the paste;
(iii) a terpene resin;
, and the content of terpene resin is 2.3 times or less of the content of rubber-based polymer.
[Item 2] The patch according to Item 1, wherein the terpene resin is contained in an amount of 30% to 40% by weight based on the total weight of the plaster.
[Item 3] The patch according to Item 1 or 2, wherein the rubber-based polymer is a styrene-isoprene-styrene block copolymer.
[Item 4] The patch according to Item 3, wherein the styrene-isoprene-styrene block copolymer is contained in an amount of 15% by weight or more based on the total weight of the plaster.
[Item 5] The patch according to any one of Items 1 to 4, wherein the oil component is at least one selected from the group consisting of MCT oil, hemp oil, and CBD oil.
[Item 6] The patch according to any one of Items 1 to 5, wherein the plaster further contains a powder that does not dissolve in the oil and the rubber-based polymer.
[Item 7] The patch according to Item 6, wherein the powder is silicic anhydride.
[Item 8] The patch according to any one of Items 1 to 7, wherein the plaster further contains liquid paraffin.
[Item 9] A patch having a plaster provided on one side of a support, the plaster comprising:
(i) an oil content that is liquid at room temperature in an amount of 20% by weight or more based on the total weight of the plaster;
(ii) a rubber-based polymer in an amount of 5% to 20% by weight based on the total weight of the paste;
(iii) a terpene resin;
(iv) a powder that does not dissolve in the oil and the rubber-based polymer;
(v) liquid paraffin;
, and the content of terpene resin is 2.3 times or less of the content of rubber-based polymer.

According to the present invention, it is possible to provide a patch that contains a certain amount or more of an oil that is liquid at room temperature and has well-balanced tack, cohesive force, and adhesive force. The patch of the present invention exhibits excellent tack and adhesive strength to the skin when applied, and also exhibits cohesive strength that allows it to be easily peeled off so that no paste remains on the skin when removed.

In the patch of the present invention, a plaster is provided on one side of the support.

(Support)
The support may be any support as long as it can hold the paste, and those commonly used for adhesive patches can be used. Examples of the support include woven fabric, nonwoven fabric, and resin film. Further, the support may be a laminate of a woven fabric and a film, a laminate of a nonwoven fabric and a film, for example, a nonwoven laminate film in which a nonwoven fabric is laminated to a polyester film or a PET film.

Examples of the material for the support include polyester (polyethylene terephthalate (PET), polyethylene isophthalate, polypropylene terephthalate, polypropylene isophthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polyolefin (ethylene, propylene, vinyl acetate, or acrylonitrile). Polyamides (such as nylon or silk), polyurethane (PU), and cellulose (such as cotton or hemp) may be mentioned.

(plaster)
A plaster is a drug-containing layer (matrix) that is solid or semi-solid at room temperature. The paste of the present invention contains an oil that is liquid at room temperature in an amount of 20% by weight or more based on the total weight of the paste, a rubber-based polymer in an amount of 5% to 20% by weight based on the total weight of the paste, and a terpene resin. (Here, the content of the terpene resin is 2.3 times or less than the content of the rubber-based polymer.)

(Liquid oil at room temperature)
An oil that is liquid at room temperature means an oil that is fluid at about 25°C. Oils that are liquid at room temperature include lipids that are made up of ester bonds of glycerin and unsaturated fatty acids. The oil may be extracted from natural ingredients or may contain synthetic lipids, as long as it is suitable for administration as a patch.
Examples of oils that are liquid at room temperature include oils extracted from plants. Specific examples of oils that are liquid at room temperature include argan oil, avocado oil, canola oil, peanut oil, camellia oil, safflower oil, rapeseed oil, coconut oil, cottonseed oil, jojoba oil, flaxseed oil, corn oil, hazelnut oil, Olive oil, orange oil, palm oil, rose oil, banana oil, vanilla oil, castor oil, sesame oil, sunflower oil, hemp oil, CBD oil, MCT oil, safflower oil, flaxseed oil, mint oil, peppermint oil, lavender oil, lemon Examples include oil. One or more types of oils that are liquid at room temperature may be used in combination. In the present invention, the oil that is liquid at room temperature is preferably MCT oil, hemp oil, CBD oil, or a combination thereof.
The content of oil that is liquid at room temperature is, for example, 20% by weight or more based on the total weight of the paste. The content may be 25% by weight or more, 30% by weight or more, or 35% by weight or more, and 50% by weight or less, 45% by weight or less, or 40% by weight or less, based on the total weight of the paste. You can also use it as The content of oil that is liquid at room temperature is, for example, 20% to 50% by weight, 20% to 45% by weight, 20% to 40% by weight, 25% by weight based on the total weight of the paste. ~50wt%, 25wt%~45wt%, 25wt%~40wt%, 30wt%~50wt%, 30wt%~45wt%, 30wt%~40wt%, 35wt%~50 % by weight, 35% by weight to 45% by weight, or 35% to 40% by weight. The content is 20% by weight, 21% by weight, 22% by weight, 23% by weight, 24% by weight, 25% by weight, 26% by weight, 27% by weight, 28% by weight based on the total weight of the paste. %, 29% by weight, 30% by weight, 31% by weight, 32% by weight, 33% by weight, 34% by weight, 35% by weight, 36% by weight, 37% by weight, 38% by weight, 39% by weight, 40% by weight, It may be 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49% or 50% by weight.
In the present invention, the oil that is liquid at room temperature may or may not exhibit physiological activity. The patch of the present invention may contain an oil that is liquid at room temperature as an active ingredient, or may contain an ingredient other than an oil that is liquid at room temperature as an active ingredient, or an oil that is liquid at room temperature as an active ingredient. and may contain other ingredients.

(Rubber polymer)
The rubber-based polymer is an adhesive that forms a paste. Examples of rubber-based polymers include styrene-isoprene-styrene block copolymer (hereinafter sometimes referred to as "SIS"), styrene-butadiene-styrene block copolymer, and styrene-ethylene-butadiene rubber-styrene block copolymer. Synthetic rubbers such as synthetic rubber, styrene-butadiene rubber, polyisoprene, polyisobutylene, polybutene, butyl rubber, and silicone rubber; and natural rubber. The rubber-based polymer is preferably SIS.
The content of the rubber-based polymer is, for example, 5% to 20% by weight based on the total weight of the paste. For example, its content may be 10% to 19% by weight or 13% to 18% by weight.

As long as the paste contains the rubber polymer within the above range, it may also contain other adhesives such as acrylic polymers and silicone polymers as long as they do not impede the effects of the present invention.
Examples of acrylic polymers include polyacrylic acid methyl ester, polymethacrylic acid methyl ester, and the like. Specific examples include DURO-TAK87-2097, 87-2194, 87-2196, 87-2287, 87-2516, 87-2852, 87-235A (product name, manufactured by Henkel Japan Co., Ltd.), Nissetsu KP- 77, AS-370 (trade name, manufactured by Nippon Carbide Industries Co., Ltd.), and the like.
Examples of silicone-based polymers include dimethylpolysiloxane, diphenylpolysiloxane, and the like.

(terpene resin)
Terpene resin is a tackifier that gives adhesiveness to the paste.
The content of the terpene resin is, for example, 2.3 times or less than the content of the rubber-based polymer. Further, its content may be 2.25 times or less or 2.2 times or less. By setting the content of the terpene resin within this range, it is possible to obtain a patch that is excellent in tack, cohesive force, and adhesive force in a well-balanced manner.
The content of the terpene resin is, for example, 30% to 40% by weight based on the total weight of the paste. For example, its content may be 32% to 39% by weight or 33% to 38% by weight.

(Tackifier)
As long as the paste contains the terpene resin within the above range, it may contain other tackifiers as long as they do not impede the effects of the present invention.
Examples of the tackifier include alicyclic hydrocarbon resins, aliphatic hydrocarbon resins, polystyrene resins, rosin, hydrogenated rosin, and the like.

(powder)
The paste may further contain a powder that does not dissolve in the oil and rubber-based polymer, which are liquid at room temperature. In the present invention, the powder may contribute to the formation of voids in the paste.
The powder is not particularly limited as long as it is a solid powder reagent (filler) used in the plaster of the patch, and examples thereof include silicic anhydride, crystalline cellulose, zinc oxide, titanium oxide, kaolin, and Examples include calcium carbonate, and further examples include wheat flour, starch powder such as corn starch, carmellose, carmellose metal salt, agar, carrageenan, pectin, powdered sugar, polyethylene powder, polystyrene sulfonate, and the like. In the present invention, the powder is preferably crystalline cellulose, silicic anhydride, starch, carmellose, or carmellose metal salt.
If the amount of powder added increases, the adhesive force of the patch will improve, but if the amount is too large, the patch will become hard and the adhesive force will decrease. Therefore, the preferred amount of powder added is, for example, 1 to 10% by weight, preferably 2 to 6% by weight. Furthermore, considering the voids in the paste formed by the powder, if the amount of liquid oil at room temperature is large, the amount of powder added may be large; The amount may be small.
The voids formed can be appropriately adjusted by combining a plurality of powders having different bulk densities. Therefore, it is possible to create an appropriate combination of powders corresponding to the amount of plaster to be used. For example, powders of light anhydrous silicic acid, cornstarch, crystalline cellulose, etc. can be used in combination.
The powder does not dissolve in liquid oils and rubber-based polymers at room temperature. Here, "not soluble" means insoluble, and according to the U.S. definition of solubility (U.S. Pharmacopeia National Formulary), the amount of powder is less than 1 mg per 10 g of oil or rubber polymer. This means that it does not melt.

(Additive)
The paste may further contain other additives as long as they do not impede the effects of the present invention. Examples of additives include ingestion prevention agents, softeners, antioxidants, pH adjusters, thickeners, ultraviolet absorbers, surfactants, and the like. These additives may be used alone or in combination of two or more in appropriate amounts.
Examples of the accidental ingestion prevention agent include, but are not limited to, substances having a strong bitter taste such as denatonium, with denatonium benzoate being preferred.
The content of the accidental ingestion prevention agent is, for example, 0.01 to 0.1% based on the total weight of the paste. When denatonium benzoate is included as the accidental ingestion prevention agent, the content is It is preferably about 0.01 to 0.1% based on the total weight. This amount produces a strong bitter taste when the patch is taken into the mouth, and is effective in preventing children and others from accidentally ingesting it.
A softener is an agent mixed with a rubber-based polymer such as SIS to impart flexibility. Examples of the softener include petroleum-based softeners such as polybutene, polyisobutylene, and process oil, fatty oil-based softeners such as coconut oil and castor oil, refined lanolin, and liquid paraffin. Softeners are preferably polybutenes and liquid paraffins. The content of the softener in the patch of the present invention can be adjusted as appropriate depending on the type of softener, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. Moreover, one kind or two or more kinds of softeners may be used together.
Examples of antioxidants include organic antioxidants such as dibutylhydroxyltoluene (BHT), propyl gallate, and sodium ascorbate, and inorganic antioxidants such as sodium thiosulfate, sodium bisulfite, sodium sulfite, and sodium pyrosulfite. Examples include agents. The content of the antioxidant in the patch of the present invention can be adjusted as appropriate depending on the type of antioxidant, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. Moreover, one kind or two or more kinds of antioxidants may be used together.
The pH adjuster may be any acid or base or a salt thereof that is commonly used for pH adjustment in the pharmaceutical field, such as hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, gluconic acid, and succinic acid. Acid, acetic acid, methanesulfonic acid, edetic acid, aqueous ammonia, monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, meglumine, trometamol, glycine, potassium hydroxide, calcium hydroxide, sodium hydroxide, Examples include magnesium hydroxide, sodium citrate, sodium acetate, sodium hydrogen carbonate, potassium hydrogen carbonate, and sodium carbonate. The content of the pH adjuster in the patch of the present invention can be adjusted as appropriate depending on the type of pH adjuster, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. Moreover, one kind or two or more kinds of pH adjusters may be used together.
Thickeners include, but are not limited to, carbopol and the like. The content of the thickener in the patch of the present invention can be adjusted as appropriate depending on the type of thickener, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. Moreover, one kind or two or more kinds of thickeners may be used together.
Examples of the ultraviolet absorber include, but are not limited to, 2-hydroxy-4-methoxybenzophenone, t-butylmethoxydibenzoylmethane, para-aminobenzoic acid, and the like. The content of the ultraviolet absorber in the adhesive patch of the present invention can be adjusted as appropriate depending on the type of ultraviolet absorber, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. Moreover, one type or two or more types of ultraviolet absorbers may be used together.
Surfactants include, but are not limited to, nonionic surfactants such as sorbitan monolaurate, anionic surfactants such as sodium lauryl sulfate, cationic surfactants such as benzalkonium chloride, Examples include amphoteric surfactants such as uryldimethylaminoacetic acid betaine. The content of surfactant in the adhesive patch of the present invention can be adjusted as appropriate depending on the type of surfactant, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. Moreover, one type or two or more types of surfactants may be used together.

(Release liner)
The adhesive patch of the present invention may further include a release liner on the opposite side of the plaster provided with the support. A release liner can protect the patch until it is applied to the skin. Release liners include, for example, polyolefins such as polyethylene and polypropylene; ethylene-vinyl acetate copolymers, vinyl acetate-vinyl chloride copolymers, polyvinyl chloride, etc.; polyamides such as nylon; polyesters such as polyethylene terephthalate; cellulose derivatives; Examples include synthetic resins such as polyurethane, films or sheets made of materials such as aluminum and paper, and laminates thereof.

(Method for manufacturing patch)
The method for producing the patch of the present invention involves coating a release film or support with a coating solution obtained by mixing a paste material containing a liquid oil, a rubber-based polymer, and a terpene resin with a solvent at room temperature. and drying.
For example, a coating solution obtained by mixing a paste material containing liquid oil, rubber-based polymer, and terpene resin at room temperature with a solvent is applied to a release liner such as silicone-treated PET film, and then heated and dried. A patch can be produced by laminating the paste obtained by removing the solvent on a support such as a woven fabric, a nonwoven fabric, or a nonwoven laminated PET film. Alternatively, a patch can also be produced by applying a coating solution to a support, removing the solvent by heating and drying, and then laminating a release liner onto a paste.
The obtained patch may be packaged in a suitable package. Examples of the packaging body include a film bag, and the film is preferably a multilayer film, more preferably an aluminum laminate film, and the innermost layer thereof is preferably polyethylene, polypropylene, or PET.

Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited by these Examples.

Example: Evaluation test of tack, cohesive force and adhesive force of patch (1) Preparation of test preparation Each component was weighed according to the composition shown in Tables 1 and 2 below, and the compositions of Examples 1 to 2 and Comparative Examples 1 to 7 were A patch was prepared. Comparative Examples 1 and 2 used an acrylic polymer (DURO TAK387-2054, manufactured by Henkel Japan Co., Ltd.) instead of a rubber polymer (SIS-5002, manufactured by JSR Clayton Elastomer Co., Ltd.), In Comparative Examples 3 to 7, the ratio of terpene resin (PX-1150N, manufactured by Yasuhara Chemical Co., Ltd.)/SIS was adjusted. In the table, liquid paraffin is Hycol M-352 (manufactured by Kaneda Corporation), oil A is MCT oil (GTCC-LQ-(SG), manufactured by Croda Japan Co., Ltd.), and oil B is coconut oil extract. FR00027 (provided by Functional Remedies LLC), Oil C is a commercial product (CANNAPRESSO CBD oil 10ml) containing 10% by volume of cannabidiol in MCT oil.
Specifically, the weighed components are mixed, ethyl acetate is added as a solvent to prepare a coating solution, the coating solution is applied to a silicone-treated PET film (release liner), and then heated and dried. A woven fabric (support) was attached to the plaster obtained in step 1, and laminated at about 85° C. to prepare each patch.

(2) Evaluation method Each patch was applied to the forearm and peeled off, and tack, cohesive force, and adhesive force were evaluated. The evaluation criteria for tack, cohesion and adhesive strength are as follows.
<Tack (characteristic that sticks immediately when pasted and exhibits the minimum necessary adhesive strength (instant adhesive strength))>
〇: Appropriate adhesive strength and difficult to peel off.
Δ: In the case of SIS, it peels off somewhat easily. In the case of DUROTAK, the adhesive strength is too strong and it is difficult to peel off.
×: Easy to peel off.
<Cohesive force (necessary property to maintain its shape as an adhesive (paste) and prevent it from flowing)>
○: No plaster remains on the skin when peeled off.
△: No plaster remains, but stickiness is felt at the peeled site.
×: A plaster remains on the skin upon peeling.
<Adhesive strength (force to resist when peeling off from the skin, property that is a measure of adhesive strength (adhesive strength))>
○: Easy to remove, but sticks to the skin for a long time.
△: No pain is felt, but there is resistance when peeling off.
×: The resistance when peeled off from the skin is large and pain is felt.

The test results are shown in Tables 3 and 4.

As shown in the table above, Comparative Examples 1 and 2 using the acrylic polymer (DUROTAK) were inferior in all properties of tack, cohesive force, and adhesive force. All patches using rubber-based polymers (SIS) had excellent tack and cohesive force, but those in which the content of terpene resin was 2.3 times or more the content of SIS (Comparative Examples 3 to 7) However, when it was removed from the skin, some resistance was felt and the feeling of use was poor. On the other hand, the patches of Examples 1 and 2, in which the content of terpene resin was 2.3 times or less relative to the content of SIS, adhered to the skin immediately when applied and remained stuck for a long time. However, it was also easy to peel off and had an excellent usability.

The present invention can provide a patch that contains a certain amount or more of an oil that is liquid at room temperature and has well-balanced tack, cohesive force, and adhesive force. The patch of the present invention exhibits excellent tack and adhesive strength to the skin when applied, and also exhibits cohesive strength that allows it to be easily peeled off so that no paste remains on the skin when removed.

Claims

A patch comprising a plaster provided on one side of a support, the plaster comprising:
(i) an oil content that is liquid at room temperature in an amount of 20% by weight or more based on the total weight of the plaster;
(ii) a rubber-based polymer in an amount of 5% to 20% by weight based on the total weight of the paste;
(iii) a terpene resin;
, and the content of terpene resin is 2.3 times or less of the content of rubber-based polymer.
The patch according to claim 1, wherein the terpene resin is contained in an amount of 30% to 40% by weight based on the total weight of the plaster.
The adhesive patch according to claim 1, wherein the rubber-based polymer is a styrene-isoprene-styrene block copolymer.
The adhesive patch according to claim 3, wherein the styrene-isoprene-styrene block copolymer is contained in an amount of 15% by weight or more based on the total weight of the plaster.
The patch according to claim 3, wherein the oil is at least one selected from the group consisting of MCT oil, hemp oil, and CBD oil.
The adhesive patch according to claim 1, wherein the paste further contains a powder that does not dissolve in the oil and the rubber-based polymer.
The patch according to claim 6, wherein the powder is silicic anhydride.
The patch according to claim 1, wherein the plaster further contains liquid paraffin.
A patch comprising a plaster provided on one side of a support, the plaster comprising:
(i) an oil content that is liquid at room temperature in an amount of 20% by weight or more based on the total weight of the plaster;
(ii) a rubber-based polymer in an amount of 5% to 20% by weight based on the total weight of the paste;
(iii) a terpene resin;
(iv) a powder that does not dissolve in the oil and the rubber-based polymer;
(v) liquid paraffin;
, and the content of terpene resin is 2.3 times or less of the content of rubber-based polymer.