WO2006057375A1 - Medicinal preparation for external use - Google Patents

Medicinal preparation for external use Download PDF

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Publication number
WO2006057375A1
WO2006057375A1 PCT/JP2005/021754 JP2005021754W WO2006057375A1 WO 2006057375 A1 WO2006057375 A1 WO 2006057375A1 JP 2005021754 W JP2005021754 W JP 2005021754W WO 2006057375 A1 WO2006057375 A1 WO 2006057375A1
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WO
WIPO (PCT)
Prior art keywords
diol
propane
methyl
external preparation
menthyloxy
Prior art date
Application number
PCT/JP2005/021754
Other languages
French (fr)
Japanese (ja)
Inventor
Ikuhiro Kakubari
Ken-Ichi Noguchi
Miyuki Ikeda
Original Assignee
Saitama Daiichi Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Saitama Daiichi Pharmaceutical Co., Ltd. filed Critical Saitama Daiichi Pharmaceutical Co., Ltd.
Publication of WO2006057375A1 publication Critical patent/WO2006057375A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0208—Tissues; Wipes; Patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/24—Thermal properties
    • A61K2800/244—Endothermic; Cooling; Cooling sensation

Definitions

  • the present invention relates to an external preparation containing a medicinal component and a refreshing glaze that does not substantially affect the transdermal absorption rate of the medicinal component.
  • menthols such as 1 menthol and hat power oil have been generally used as a refreshing agent to be blended in external preparations.
  • Menthols and chimney oils are highly sublimable and have a odor and odor, so they emit a strong odor especially when formulated in patches such as poultices and tapes. Therefore, topical preparations in the form of patches containing menthols and power oils can cause problems such as stinking around and causing odors to stick to clothes and hair. have. Because of this problem, the patient himself / herself restricted the use of the patch, or peeled off the patch even though the treatment was not completed. Often there were serious situations.
  • the heartbeat odor possessed by menthols such as 1 menthol has the effect of reducing appetite and suppressing gastric juice secretion.
  • topical preparations such as a skin lotion
  • the user had a loss of appetite due to a pungent odor, sometimes causing nausea and vomiting.
  • menthols such as 1-menthol are solid at room temperature
  • crystals may form over time, or a cooling agent may be present uniformly in the preparation.
  • Oil and coconut oil contain about 50% menthol, and the same problem as above occurs when using Hatsu power oil as a cooling agent.
  • oil and coconut oil are natural products, there is another problem that the stability of the product standard is often lacking because the components are often non-uniform.
  • menthols such as heart force oil and 1 menthol have the effect of promoting the percutaneous absorption of drugs, as well as force 3-1 (menthoxypropane 1,2 diol). It has the effect of promoting percutaneous absorption of medicinal ingredients, and the cumulative permeation amount of medicinal ingredients in percutaneous absorption shows a significant increase depending on the concentration of the above substances. Therefore, in order to control the cumulative permeation amount of medicinal ingredients over a long period of time, the amount of 3-1- (menthoxypropane 1,2 diol) must be limited, which reduces the refreshing feeling, etc. There was a problem. For these reasons, there has been a strong demand to provide a preparation for external use that contains a strawberry refreshing agent that has reduced volatility and strong odor, and that does not substantially affect the transdermal absorption rate of medicinal ingredients. It was.
  • An object of the present invention is to provide an external preparation that solves the above-mentioned problems. More specifically, an irritating odor such as a heartbeat odor is suppressed, and a medicinal component is percutaneously absorbed.
  • the object is to provide an external preparation containing a refreshing agent that does not substantially affect the speed.
  • Means for solving the problem [0007] The present inventors diligently searched for a refreshing agent that has a suppressed strong odor and does not substantially affect the transdermal absorption rate of a medicinal component contained in an external preparation. It has been found that a group of refreshing agents represented by methyl 3- (1-menthyloxy) propane 1,2 diol or derivatives thereof has the desirable properties described above. Conventionally, the above
  • an external preparation in which (1) the medicinal component and (2) the heartbeat odor are suppressed, and the percutaneous absorption rate of the medicinal component is substantially affected.
  • An external preparation containing a refreshing agent that is not given is provided.
  • the refreshing agent is 2-methyl-3- (1 menthoxy) propane mono: L, 2-diol or a derivative thereof described above; the refreshing agent is 2-methyl- 3— (1 Menthyloxy) propane 1,2 diol as described above External preparation, wherein the amount of the refreshing agent is 0.001 to 20% by weight based on the total composition of the external preparation Formulation; the medicinal component is a non-steroidal anti-inflammatory agent, skeletal muscle relaxant, and vasodilator power
  • the refreshing agent contained in the external preparation of the present invention is excellent in that it does not substantially affect the percutaneous absorption rate of the medicinal component of the external preparation in addition to the suppression of the heartbeat odor. It has a nature. Therefore, in the preparation for external use of the present invention, the blending ratio of the above-mentioned refreshing agent with respect to the medicinal component can be greatly increased as compared with the conventional preparation for external use. In addition, it can be used as an external preparation excellent in refreshing feeling. In addition, since the percutaneous absorption rate of medicinal ingredients is not affected, formulation design is facilitated. Moreover, the preparation for external use of the present invention containing a large amount of the above-mentioned refreshing agent does not cause discomfort to the patient who has almost no irritating odor such as odor or cough odor.
  • the preparation for external use of the present invention comprises (1) a medicinal component, and (2) a refreshing agent that suppresses the heartbeat odor and does not substantially affect the transdermal absorption rate of the medicinal component. It is characterized by including.
  • the kind of the medicinal component in the external preparation of the present invention is not particularly limited.
  • Non-steroidal anti-inflammatory drugs such as piroxicam, meloxicam, diclofenac and its salts, loxoprofen and its salts, suprofen, zaltoprofen, thiaprofen, tenidap and their derivatives, antiallergic agents such as trast, ketotifen, azelastine and ibudilast , Skeletal muscle relaxants such as eperisone hydrochloride, tolperisone, tizarin and pridinol, antihistamines such as diphenhydramine and chlorfelamin, nitroglycerin, glass Vasodilators such as isosorbide, salt-carp mouthpiece, minoxidil, local anesthetics such as lidocaine, pro-in hydrochloride, benzocaine, antifungal agents such as miconazole, clotrimazole, butenafine hydrochloride, bifonazole, hydrochloric acid Examples include dysuria such as
  • a refreshing agent that suppresses the heartbeat odor and does not substantially affect the percutaneous absorption rate of medicinal ingredients for example, 2-methyl 3- (1-menthyloxy) propane-1
  • the ability to preferably use 2-diol or a derivative thereof is not limited to these specific substances.
  • V or any other refreshing agent may be used as long as it has a property that suppresses the heart odor and does not substantially affect the transdermal absorption rate of the medicinal component.
  • 2-Methyl-3- (1 menthyloxy) propane 1,2 diol derivative and Examples thereof include ester derivatives, alkyl derivatives, halogen derivatives, and the like. Particularly preferred is 2-methyl-3- (1-menthyloxy) propane 1,2-diol.
  • the refreshing effect of the refreshing agent used in the external preparation of the present invention is not particularly limited.
  • 1S For example, menthols, heart power oil, 3-1- (menthoxypropane-1,2 diol), or 2- It is desirable that the cooling effect is almost the same as that of conventionally known cooling agents such as methyl-3- (1 menthyloxy) propane 1,2 diol.
  • the cooling effect can be easily measured by those skilled in the art according to methods well known in the art.
  • the suppression of the heartbeat odor of the refreshing agent used in the external preparation of the present invention is, for example, tested using 2-methyl 3- (1-menthyloxy) propane 1,2-diol as a comparative control. What is necessary is just to confirm that the refreshing agent has the same or lower odor than the above substances. Such confirmation can be performed by a sensory test, for example.
  • the refreshing agent used in the external preparation of the present invention does not substantially affect the percutaneous absorption rate of the medicinal component is known to those skilled in the art by the method specifically described in the examples of the present specification. Easy to check. Although the percutaneous absorption profile differs depending on the type and dosage form of the medicinal ingredient, it cannot be generally stated.For example, in the presence of the test cooling agent, the rate of increase in the percutaneous absorption rate of the medicinal ingredient from the external preparation is increased. Less than 250 percent, preferably less than 200 percent, more preferably less than 100 percent, particularly preferably less than 50 percent, and most preferably less than 30 percent compared to the absence of the test refreshing agent.
  • the percutaneous absorption rate of a medicinal ingredient is the rate at which the medicinal ingredient contained in the external preparation per unit time is applied to the skin, mucous membrane, or scalp, etc. Is shown by the amount transmitted.
  • the unit is gZcm 2 Zhr, and it is evaluated as the transmission speed.
  • the amount of the refreshing agent blended in the external preparation of the present invention is not particularly limited, but the refreshing agent used in the external preparation of the present invention does not substantially affect the transdermal absorption rate of the medicinal component. Therefore, it is possible to increase the blending ratio of the cooling agent with respect to the medicinal ingredient compared with the conventional external preparation, thereby making the external preparation of the present invention a high refreshing feeling.
  • it contains a cooling agent
  • the amount can be selected from the viewpoint of the refreshing feeling perceived by humans and its sustainability, for example, 0.0001 to 20% by weight, preferably 0.01 to 10% by weight based on the total weight of the composition of the external preparation. %, Most preferably about 0.1 to 5% by weight.
  • the form of the external preparation of the present invention is not particularly limited, and is conventionally used as an external preparation, for example, a patch, a patch, a patch, a reservoir-type patch, a stick, etc.
  • an external preparation in the form of a solid preparation such as a gel, a semi-solid preparation such as a gel ointment, an ointment, or a time preparation, a liquid such as a lotion or liniment, or a spray such as an aerosol or non-gas spray.
  • a solid preparation such as a gel, a semi-solid preparation such as a gel ointment, an ointment, or a time preparation
  • a liquid such as a lotion or liniment
  • a spray such as an aerosol or non-gas spray.
  • the method for producing the external preparation of the present invention is not particularly limited, and a conventional production method known to those skilled in the art can be adopted depending on the form of the external preparation.
  • the ability to use one or more pharmaceutical additives The necessity and type thereof are appropriately selected by those skilled in the art depending on the form of the preparation. It is possible.
  • aqueous bases such as macrogol
  • oily bases such as petrolatum and liquid paraffin
  • Arabic gum gelatin
  • water-soluble polymers such as salt, polybulal alcohol and polybulurpyrrolidone
  • antioxidants such as erythorbic acid, sodium erythorbate, hydroxy-sol, anhydrous sodium sulfite
  • preservatives coloring agents
  • pH adjusters the present invention is not limited to these.
  • the above components were mixed in a kneader, spread on a polyester film that had been subjected to a release treatment, covered with a polyester woven fabric, and transferred by pressure bonding to obtain a tape agent.
  • the above components were mixed in a kneader, spread on a polyester film that had been subjected to a release treatment, covered with a polyester woven fabric, and transferred by pressure bonding to obtain a tape agent.
  • the above components were mixed with a kneader, spread evenly on a non-woven fabric, and pressure-bonded with a polyester film as a release liner to obtain a knocking agent.
  • the above ingredients were mixed with a mixer to obtain a lotion agent.
  • the above ingredients were mixed with a mixer to obtain a lotion agent.
  • the above components were mixed in a mixer, placed in a pressure vessel, filled with dimethyl ether, and used as an aerosol agent.
  • a gel ointment was prepared by the same formulation and production method as in Example 5 except that 2-methyl-3- (1 menthyloxy) propane 1,2 diol was not blended.
  • a gel ointment was prepared by the same formulation and production method as in Example 5, except that 1-menthol was blended instead of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
  • a gel ointment was prepared by the same formulation and production method as in Example 6 except that 1-menthol was blended in place of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
  • a gel ointment was prepared using the same formulation and production method as in Example 7, except that 1-menthol was added instead of 2-methyl-3- (1 menthyloxy) propane 1,2 diol. Made.
  • a gel ointment was prepared by the same formulation and production method as in Example 8, except that 2-methyl-3- (1 menthyloxy) propane 1,2 diol was not blended.
  • a gel ointment was prepared by the same formulation and production method as in Example 8, except that 1-menthol was blended in place of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
  • a gel ointment was prepared by the same formulation and production method as in Example 9, except that 1-menthol was blended in place of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
  • a gel ointment was prepared by the same formulation and production method as in Example 10, except that 1-menthol was blended instead of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
  • a cataplasm was prepared by the same formulation and production method as in Example 4 except that 1-menthol was blended instead of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
  • the gel ointment of Examples 5 to 10 and the gel ointment of Comparative Examples 1 to 8 were subjected to a hairless mouse skin permeation test.
  • hairless mouse-extracted skin was attached to a Franz-type cell, 0.5 mL of the preparation was applied to the donor cell, and 4 mL of phosphate buffered saline was applied to the receiver cell.
  • the experiment was performed at 32 ° C. A portion of the receiver solution was collected at regular intervals, and the amount of drug that permeated the receiver was quantified by HPLC.
  • Test results Table 1 shows the permeation rate and lag time of ketoprofen, and Table 2 shows the permeation rate and lag time of indomethacin. [0040] [Table 1]
  • ketoprofen is used as the medicinal component
  • the permeation rate of 14.8 (gZcm 2 Zhr) in Comparative Example 1 in which no refreshing agent is added is compared with 2-methyl 3- (1-menthylo) as the refreshing agent.
  • Example 5 Example 6, and Example 7 in which 0.5%, 1.0%, and 2.0% by weight of xy) propane 1,2 diol were blended, the rate of increase in permeation rate was 30%, 51 %, 84%, almost no influence on the transdermal absorption rate.
  • the permeation rate of Comparative Example 5 in which no refreshing agent is blended is 16.5 (g / cm 2 / hr), whereas the refreshing agent is 2-methyl 3— (The rate of increase in permeation rate in Examples 8, 9, and 10 containing 1-menthoxy) propane 1,2 diol was 0.5% by weight, 1.0% by weight, and 2.0% by weight, respectively. %, 61%, and 2 20%, almost no influence on the transdermal absorption rate.
  • Example 4 As is apparent from the above results, the external preparation of Example 4 containing 2-methyl-3- (1 menthyloxy) propane-1,2 diol as a refreshing agent was compared with 1 menthol. Compared to Example 9, while maintaining the same refreshing intensity, the odor intensity was about 1/6.
  • the external preparation of the present invention is an external preparation containing a refreshing agent that suppresses an irritating odor such as a heart odor and does not substantially affect the percutaneous absorption rate of a medicinal ingredient. It can be suitably used as, for example.

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Abstract

A medicinal preparation for external use which comprises (1) a medicinal ingredient and (2) a refrigerant (e.g., 2-methyl-3-(1-menthyloxy)propane-1,2-diol or a derivative thereof) which is reduced in mint odor and exerts substantially no influence on the rate of percutaneous absorption of the medicinal ingredient.

Description

外用製剤  External preparation
技術分野  Technical field
[0001] 本発明は、薬効成分と薬効成分の経皮吸収速度に実質的に影響を与えない清涼 ィ匕剤とを含有する外用製剤に関する。  [0001] The present invention relates to an external preparation containing a medicinal component and a refreshing glaze that does not substantially affect the transdermal absorption rate of the medicinal component.
背景技術  Background art
[0002] 従来、外用製剤に配合される清涼化剤としては、 1 メントールなどのメントール類 やハツ力油などが一般的に用いられている。メントール類やハツ力油は昇華性が高く 、 ノ、ッカ臭を有するために、特にパップ剤やテープ剤などの貼付剤に配合した場合 には強いにおいを発する。それゆえ、メントール類やハツ力油を配合した貼付剤の形 態の外用製剤は、周囲に悪臭を撒き散らしたり、また衣服や髪の毛に臭いを吸着さ せてしまい、におい残りを生ずるなどの問題を有している。この問題のため、患者が 貼付剤の使用を自ら制限したり、治療が完了していないにもかかわらず貼付剤を剥 力 Sしてしま 、、コンプライアンスが低下して十分な治療が行えな 、と 、う深刻な事態と なることがしばしばあった。  [0002] Conventionally, menthols such as 1 menthol and hat power oil have been generally used as a refreshing agent to be blended in external preparations. Menthols and chimney oils are highly sublimable and have a odor and odor, so they emit a strong odor especially when formulated in patches such as poultices and tapes. Therefore, topical preparations in the form of patches containing menthols and power oils can cause problems such as stinking around and causing odors to stick to clothes and hair. have. Because of this problem, the patient himself / herself restricted the use of the patch, or peeled off the patch even though the treatment was not completed. Often there were serious situations.
[0003] また、 1 メントールなどのメントール類が持つハツ力臭は、食欲を減退させたり胃液 の分泌を抑制するなどの効果を有して 、ることから、貼付剤ある 、は頭髪用製剤や 皮膚用ローション剤などの外用製剤にメントール類を配合した場合には、使用者がハ ッカ臭により食欲不振となり、ときには吐き気や嘔吐をもよおすなどの問題点があった 。さらに、 1—メントールなどのメントール類は常温において固体であることから、外用 製剤中に 1 メントールを清涼化剤として配合すると経時的に結晶が生じたり、製剤 中に清涼化剤が均一に存在できずに経時的に昇華してしま ヽ清涼感が持続しな ヽ などの問題があった。ノ、ッカ油にはメントールが約 50%含有されており、清涼化剤と してハツ力油を用いた場合にも上記と同様の問題が生じる。また、ノ、ッカ油は天然物 であることから、その成分が不均一であることが多ぐ製品規格の安定性に欠けるとい う別の問題もあった。  [0003] In addition, the heartbeat odor possessed by menthols such as 1 menthol has the effect of reducing appetite and suppressing gastric juice secretion. When menthols were added to topical preparations such as a skin lotion, the user had a loss of appetite due to a pungent odor, sometimes causing nausea and vomiting. Furthermore, since menthols such as 1-menthol are solid at room temperature, when 1 menthol is added as a cooling agent in a preparation for external use, crystals may form over time, or a cooling agent may be present uniformly in the preparation. However, there was a problem that the refreshing feeling did not last. Oil and coconut oil contain about 50% menthol, and the same problem as above occurs when using Hatsu power oil as a cooling agent. In addition, since oil and coconut oil are natural products, there is another problem that the stability of the product standard is often lacking because the components are often non-uniform.
[0004] メントールの強 、揮発性及びハツ力臭を抑制した清涼化剤として、特公平 61—488 13号公報には 3—1 （メントキシプロパン 1, 2 ジオール）が開示されており、特 許第 2852816号には上記物質を特定の薬物の溶解剤として含有する外用製剤が 開示されている。この外用製剤は、ノ、ッカ油やメントール類などのノ、ッカ臭がなぐ上 記の問題を解決した外用製剤として使用できる。しかしながら、この物質は外用製剤 中の薬効成分 (例えば抗炎症剤など)の経皮吸収速度に影響を及ぼすと!、う問題点 を有していた。すなわち、ハツ力油や 1 メントールなどのメントール類は薬物の経皮 吸収を促進する効果を有している力 3—1 （メントキシプロパン 1, 2 ジオール） もハツ力油やメントール類と同様に薬効成分の経皮吸収促進効果を有しており、経皮 吸収における薬効成分の累積透過量は上記物質の濃度に依存して顕著な増加を示 す。従って、薬効成分の累積透過量を長時間にわたってコントロールするためには 3 -1- (メントキシプロパン 1, 2 ジオール)の配合量を制限しなければならず、そ れによって清涼感が減少するなどの問題点があった。このような理由から、揮発性及 びハツ力臭が抑制されており、かつ薬効成分の経皮吸収速度に実質的に影響を与 えな ヽ清涼化剤を含む外用製剤の提供が切望されて 、た。 [0004] As a refreshing agent that suppresses the strong, volatile, and strong smell of menthol No. 13 discloses 3-1 (menthoxypropane 1,2 diol), and Japanese Patent No. 2852816 discloses an external preparation containing the above substance as a dissolving agent for a specific drug. This preparation for external use can be used as an external preparation for solving the above-mentioned problems in which the odor of mint, coconut oil, menthol, etc. is lost. However, this substance has a problem if it affects the percutaneous absorption rate of a medicinal component (for example, an anti-inflammatory agent) in an external preparation! In other words, menthols such as heart force oil and 1 menthol have the effect of promoting the percutaneous absorption of drugs, as well as force 3-1 (menthoxypropane 1,2 diol). It has the effect of promoting percutaneous absorption of medicinal ingredients, and the cumulative permeation amount of medicinal ingredients in percutaneous absorption shows a significant increase depending on the concentration of the above substances. Therefore, in order to control the cumulative permeation amount of medicinal ingredients over a long period of time, the amount of 3-1- (menthoxypropane 1,2 diol) must be limited, which reduces the refreshing feeling, etc. There was a problem. For these reasons, there has been a strong demand to provide a preparation for external use that contains a strawberry refreshing agent that has reduced volatility and strong odor, and that does not substantially affect the transdermal absorption rate of medicinal ingredients. It was.
[0005] 一方、 2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールは、上記、 3 On the other hand, 2-methyl-3- (1-menthyloxy) propane 1,2 diol is
-1- (メントキシプロパン 1, 2 ジオール)の持つ苦味を抑える目的で開発された 清涼感改善剤であり、特許第 3219995号に開示されている。この特許公報には、 2 ーメチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールからなる清涼感改善 剤が開示されており、 1 メントールと併用することにより清涼感を持続させる旨が記 載されている。また、上記特許公報には、上記物質をパップ剤に配合することについ ての示唆がある。しかしながら、上記特許公報には、この物質が外用製剤の薬効成 分の経皮吸収速度に影響を与える力否かにっ 、て何ら示唆な 、し教示はな 、。 発明の開示  -1- (Mentoxypropane 1,2 diol) is a refreshing sensation improver developed for the purpose of suppressing the bitterness of menthol and disclosed in Japanese Patent No. 3219995. This patent publication discloses a refreshing agent comprising 2-methyl-3- (1 menthyloxy) propane 1,2 diol, and states that the refreshing feeling is maintained by using it together with 1 menthol. . In addition, the above-mentioned patent publication has a suggestion about blending the above substance into a poultice. However, the above-mentioned patent publication does not suggest or teach whether or not this substance has an effect on the percutaneous absorption rate of the medicinal component of the external preparation. Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0006] 本発明の課題は、上記の問題点を解決した外用製剤を提供することにあり、より具 体的には、ハツ力臭などの刺激臭が抑制され、かつ薬効成分の経皮吸収速度に実 質的に影響を与えない清涼化剤を含む外用製剤を提供することにある。 課題を解決するための手段 [0007] 本発明者らは、ハツ力臭が抑制されており、かつ外用製剤に含まれる薬効成分の 経皮吸収速度に実質的に影響を与えない清涼化剤を鋭意探索したところ、 2—メチ ルー 3—（1 メンチルォキシ)プロパン 1, 2 ジオール又はその誘導体に代表され る一群の清涼化剤が上記の望ましい性質を有していることを見出した。従来、上記の[0006] An object of the present invention is to provide an external preparation that solves the above-mentioned problems. More specifically, an irritating odor such as a heartbeat odor is suppressed, and a medicinal component is percutaneously absorbed. The object is to provide an external preparation containing a refreshing agent that does not substantially affect the speed. Means for solving the problem [0007] The present inventors diligently searched for a refreshing agent that has a suppressed strong odor and does not substantially affect the transdermal absorption rate of a medicinal component contained in an external preparation. It has been found that a group of refreshing agents represented by methyl 3- (1-menthyloxy) propane 1,2 diol or derivatives thereof has the desirable properties described above. Conventionally, the above
2つの性質を両立させた清涼化剤の存在は全く知られていない。また、 2—メチルー 3- (1—メンチルォキシ)プロパン一 1, 2 ジオールを清涼化剤として外用製剤に適 量配合することにより、薬効成分の経皮吸収速度に実質的に影響を与えずに、極め て清涼感が高ぐしかもハツ力臭などの刺激臭のない外用製剤を提供できることを見 出した。本発明は上記の知見を基にして完成されたものである。 The existence of a refresher that balances the two properties is not known at all. In addition, by blending an appropriate amount of 2-methyl-3- (1-menthyloxy) propane-1,2 diol as a cooling agent into an external preparation, the transdermal absorption rate of the medicinal component is not substantially affected. It was found that an external preparation with an extremely refreshing sensation and no irritating odor such as heartbeat odor could be provided. The present invention has been completed based on the above findings.
[0008] すなわち、本発明により、外用製剤であって、（1)薬効成分、及び (2)ハツ力臭が抑 制されており、かつ上記薬効成分の経皮吸収速度に実質的に影響を与えない清涼 ィ匕剤を含む外用製剤が提供される。 [0008] That is, according to the present invention, there is provided an external preparation, in which (1) the medicinal component and (2) the heartbeat odor are suppressed, and the percutaneous absorption rate of the medicinal component is substantially affected. An external preparation containing a refreshing agent that is not given is provided.
本発明の好ましい態様によれば、上記清涼化剤が 2—メチルー 3—（1 メンチルォ キシ)プロパン一： L, 2—ジオール又はその誘導体である上記の外用製剤；上記清涼 化剤が 2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールである上記 の外用製剤；上記清涼化剤の配合量が、外用製剤の組成物全重量に対して 0. 000 1〜20重量％である上記の外用製剤;薬効成分が、非ステロイド系抗炎症剤、骨格 筋弛緩剤、及び血管拡張剤力 なる群力 選ばれる 1又は 2以上の薬効成分である 上記の外用製剤;パップ剤、テープ剤、パッチ剤、若しくはリザーバー型パッチ剤な どの貼付剤、スティック剤などの固形製剤、ゲル軟膏剤、軟膏剤、若しくはクリーム剤 などの半固形製剤、ローション剤若しくはリニメント剤などの液剤、又はエアゾール剤 若しくはノンガススプレー剤などのスプレー剤の形態である上記の外用製剤が提供さ れる。  According to a preferred embodiment of the present invention, the refreshing agent is 2-methyl-3- (1 menthoxy) propane mono: L, 2-diol or a derivative thereof described above; the refreshing agent is 2-methyl- 3— (1 Menthyloxy) propane 1,2 diol as described above External preparation, wherein the amount of the refreshing agent is 0.001 to 20% by weight based on the total composition of the external preparation Formulation; the medicinal component is a non-steroidal anti-inflammatory agent, skeletal muscle relaxant, and vasodilator power One or two or more medicinal components selected from the above External preparations: Patches, tapes, patches Or solid preparations such as reservoir patches, solid preparations such as sticks, semi-solid preparations such as gel ointments, ointments, or creams, liquids such as lotions or liniments, or aerosols Ku is above external preparations are provided in the form of sprays, such as non-gas spray.
発明の効果  The invention's effect
[0009] 本発明の外用製剤に含まれる清涼化剤は、ハツ力臭が抑制されていることに加えて 、外用製剤の薬効成分の経皮吸収速度に実質的に影響を与えないという優れた性 質を有している。従って、本発明の外用製剤では、薬効成分に対する上記清涼化剤 の配合比率を従来の外用製剤に比べて大幅に高めることができ、それによつて非常 に清涼感に優れた外用製剤として使用することができる。また、薬効成分の経皮吸収 速度に影響を与えないことから、製剤設計が容易となる。しかも、上記清涼化剤を大 量に含む本発明の外用製剤は、ノ、ッカ臭などの刺激臭がほとんどなぐ患者に不快 感を感じさせることがない。 [0009] The refreshing agent contained in the external preparation of the present invention is excellent in that it does not substantially affect the percutaneous absorption rate of the medicinal component of the external preparation in addition to the suppression of the heartbeat odor. It has a nature. Therefore, in the preparation for external use of the present invention, the blending ratio of the above-mentioned refreshing agent with respect to the medicinal component can be greatly increased as compared with the conventional preparation for external use. In addition, it can be used as an external preparation excellent in refreshing feeling. In addition, since the percutaneous absorption rate of medicinal ingredients is not affected, formulation design is facilitated. Moreover, the preparation for external use of the present invention containing a large amount of the above-mentioned refreshing agent does not cause discomfort to the patient who has almost no irritating odor such as odor or cough odor.
発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION
[0010] 本発明の外用製剤は、（1)薬効成分、及び (2)ハツ力臭が抑制されており、かつ上 記薬効成分の経皮吸収速度に実質的に影響を与えない清涼化剤を含むことを特徴 としている。本発明の外用製剤における薬効成分の種類は特に限定されないが、例 えば、ヒドロコルチゾン、プレド-ゾロン、デキサメタゾン、トリアムシノロン、ベタメタゾン 等のステロイド系抗炎症剤、サリチル酸グリコール、インドメタシン、ケトプロフェン、フ ルルビプロフェン、フエルビナク、ピロキシカム、メロキシカム、ジクロフェナク及びその 塩、ロキソプロフェン及びその塩、スプロフェン、ザルトプロフェン、チアプロフェン、テ ニダップ等の非ステロイド系抗炎症剤及びその誘導体、トラ-スト、ケトチフェン、ァゼ ラスチン、イブジラスト等の抗アレルギー剤、塩酸エペリゾン、トルペリゾン、チザ-ジ ン、プリジノール等の骨格筋弛緩剤、ジフェンヒドラミン、クロルフエ-ラミン等の抗ヒス タミン剤、ニトログリセリン、硝酸イソソルビド、塩ィ匕カルプ口-ゥム、ミノキシジル等の 血管拡張剤、リドカイン、塩酸プロ力イン、ベンゾカイン等の局所麻酔剤、ミコナゾー ル、クロトリマゾール、塩酸ブテナフィン、ビフォナゾール等の抗真菌剤、塩酸ォキシ プチニン、塩酸タムスロシン、塩酸リトドリン等の排尿障害剤、ニトラゼバム、ジァゼパ ム等の抗てんかん剤が挙げられる。これらの薬効成分を 2種以上組み合わせて用い てもよい。これらのうち、非ステロイド系抗炎症剤及びその誘導体、骨格筋弛緩剤、及 び血管拡張剤からなる群力 選ばれる 1又は 2以上の薬効成分が好ましい。  [0010] The preparation for external use of the present invention comprises (1) a medicinal component, and (2) a refreshing agent that suppresses the heartbeat odor and does not substantially affect the transdermal absorption rate of the medicinal component. It is characterized by including. The kind of the medicinal component in the external preparation of the present invention is not particularly limited. Non-steroidal anti-inflammatory drugs such as piroxicam, meloxicam, diclofenac and its salts, loxoprofen and its salts, suprofen, zaltoprofen, thiaprofen, tenidap and their derivatives, antiallergic agents such as trast, ketotifen, azelastine and ibudilast , Skeletal muscle relaxants such as eperisone hydrochloride, tolperisone, tizarin and pridinol, antihistamines such as diphenhydramine and chlorfelamin, nitroglycerin, glass Vasodilators such as isosorbide, salt-carp mouthpiece, minoxidil, local anesthetics such as lidocaine, pro-in hydrochloride, benzocaine, antifungal agents such as miconazole, clotrimazole, butenafine hydrochloride, bifonazole, hydrochloric acid Examples include dysuria such as oxypeptinine, tamsulosin hydrochloride, ritodrine hydrochloride, and antiepileptic agents such as nitrazebam and diazepam. Two or more of these medicinal ingredients may be used in combination. Of these, one or more medicinal ingredients selected from the group power consisting of non-steroidal anti-inflammatory agents and derivatives thereof, skeletal muscle relaxants, and vasodilators are preferred.
[0011] ハツ力臭が抑制されており、かつ薬効成分の経皮吸収速度に実質的に影響を与え ない清涼化剤としては、例えば、 2—メチル 3— (1—メンチルォキシ)プロパン一 1, 2—ジオール又はその誘導体を好ましく用いることができる力 これらの特定の物質 に限定されることはない。ハツ力臭が抑制されており、かつ薬効成分の経皮吸収速度 に実質的に影響を与えな 、性質を有する清涼化剤であれば、 V、かなるものを用いて もよい。 2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの誘導体と しては、エステル誘導体、アルキル誘導体、ハロゲン誘導体などを挙げることができる 力 その種類は特に限定されない。特に好ましいのは 2—メチルー 3—（1 メンチル ォキシ）プロパン 1 , 2—ジオールである。 [0011] As a refreshing agent that suppresses the heartbeat odor and does not substantially affect the percutaneous absorption rate of medicinal ingredients, for example, 2-methyl 3- (1-menthyloxy) propane-1, The ability to preferably use 2-diol or a derivative thereof is not limited to these specific substances. V or any other refreshing agent may be used as long as it has a property that suppresses the heart odor and does not substantially affect the transdermal absorption rate of the medicinal component. 2-Methyl-3- (1 menthyloxy) propane 1,2 diol derivative and Examples thereof include ester derivatives, alkyl derivatives, halogen derivatives, and the like. Particularly preferred is 2-methyl-3- (1-menthyloxy) propane 1,2-diol.
[0012] 本発明の外用製剤に用いる清涼化剤の清涼化効果については特に限定されない 1S 例えば、メントール類、ハツ力油、 3 -1- (メントキシプロパン一 1, 2 ジオール） 、又は 2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールなどの従来 公知の清涼化剤の清涼化効果とほぼ同等であることが望ましい。清涼化効果は当業 界で周知の方法に従って当業者が容易に測定可能である。本発明の外用製剤に用 いる清涼化剤のハツ力臭が抑制されていることは、例えば、 2—メチル 3— (1—メン チルォキシ)プロパン 1, 2—ジオールを比較対照として用いて、被験清涼化剤の ノ、ッカ臭が上記物質と同等又はそれ以下のノ、ッカ臭であることを確認すればよい。こ のような確認は、例えば官能試験により行うことができる。 [0012] The refreshing effect of the refreshing agent used in the external preparation of the present invention is not particularly limited. 1S For example, menthols, heart power oil, 3-1- (menthoxypropane-1,2 diol), or 2- It is desirable that the cooling effect is almost the same as that of conventionally known cooling agents such as methyl-3- (1 menthyloxy) propane 1,2 diol. The cooling effect can be easily measured by those skilled in the art according to methods well known in the art. The suppression of the heartbeat odor of the refreshing agent used in the external preparation of the present invention is, for example, tested using 2-methyl 3- (1-menthyloxy) propane 1,2-diol as a comparative control. What is necessary is just to confirm that the refreshing agent has the same or lower odor than the above substances. Such confirmation can be performed by a sensory test, for example.
[0013] 本発明の外用製剤に用いる清涼化剤が薬効成分の経皮吸収速度に実質的に影 響を与えないことは、本明細書の実施例に具体的に説明した方法により当業者が容 易に確認できる。薬効成分の種類、剤型によって、経皮吸収プロファイルが異なるた め一概には言えないが、例えば、被験清涼化剤の存在下において、外用製剤からの 薬効成分の経皮吸収速度の増加率が被験清涼化剤の非存在下に比べて 250パー セント未満、好ましくは 200パーセント未満、さらに好ましくは 100パーセント未満、特 に好ましくは 50パーセント未満、最も好ましくは 30パーセント未満である。本明細書 において、薬効成分の経皮吸収速度とは、外用製剤を皮膚、粘膜、又は頭皮などの 外皮に適用した場合にぉ 、て、外用製剤に含まれる薬効成分が単位時間当りに外 皮を透過した量によって示される。通常、その単位は gZcm2Zhrであり、透過速 度として評価される。 [0013] The fact that the refreshing agent used in the external preparation of the present invention does not substantially affect the percutaneous absorption rate of the medicinal component is known to those skilled in the art by the method specifically described in the examples of the present specification. Easy to check. Although the percutaneous absorption profile differs depending on the type and dosage form of the medicinal ingredient, it cannot be generally stated.For example, in the presence of the test cooling agent, the rate of increase in the percutaneous absorption rate of the medicinal ingredient from the external preparation is increased. Less than 250 percent, preferably less than 200 percent, more preferably less than 100 percent, particularly preferably less than 50 percent, and most preferably less than 30 percent compared to the absence of the test refreshing agent. In this specification, the percutaneous absorption rate of a medicinal ingredient is the rate at which the medicinal ingredient contained in the external preparation per unit time is applied to the skin, mucous membrane, or scalp, etc. Is shown by the amount transmitted. Usually, the unit is gZcm 2 Zhr, and it is evaluated as the transmission speed.
[0014] 本発明の外用製剤に配合される清涼化剤の量は特に限定されないが、本発明の 外用剤に用いられる清涼化剤は薬効成分の経皮吸収速度に実質的に影響を与えな いという性質を有していることから、従来の外用製剤に比べて、薬効成分に対する清 涼化剤の配合割合を高めることができ、それにより本発明の外用製剤を高い清涼感 を有する外用製剤として提供することが可能になる。一般的には、清涼化剤の配合 量はヒトが感じる清涼感及びその持続性等の観点力も選択することができ、例えば、 外用製剤の組成物全重量に対して 0. 0001〜20重量％、好ましくは 0. 01〜10重 量％、最も好ましくは 0. 1〜5重量％程度である。 [0014] The amount of the refreshing agent blended in the external preparation of the present invention is not particularly limited, but the refreshing agent used in the external preparation of the present invention does not substantially affect the transdermal absorption rate of the medicinal component. Therefore, it is possible to increase the blending ratio of the cooling agent with respect to the medicinal ingredient compared with the conventional external preparation, thereby making the external preparation of the present invention a high refreshing feeling. Can be provided as. Generally, it contains a cooling agent The amount can be selected from the viewpoint of the refreshing feeling perceived by humans and its sustainability, for example, 0.0001 to 20% by weight, preferably 0.01 to 10% by weight based on the total weight of the composition of the external preparation. %, Most preferably about 0.1 to 5% by weight.
[0015] 本発明の外用製剤の形態は特に制限されず、従来より外用製剤として使用されて いる製剤形態、例えば、パップ剤、テープ剤、パッチ剤、若しくはリザーバー型パッチ 剤などの貼付剤、スティック剤などの固形製剤、ゲル軟膏剤、軟膏剤、若しくはタリー ム剤などの半固形剤、ローション剤若しくはリニメント剤などの液剤、又はエアゾール 剤若しくはノンガススプレー剤などのスプレー剤等の形態の外用製剤として提供する ことができる。 [0015] The form of the external preparation of the present invention is not particularly limited, and is conventionally used as an external preparation, for example, a patch, a patch, a patch, a reservoir-type patch, a stick, etc. As an external preparation in the form of a solid preparation such as a gel, a semi-solid preparation such as a gel ointment, an ointment, or a time preparation, a liquid such as a lotion or liniment, or a spray such as an aerosol or non-gas spray. Can be provided.
[0016] 本発明の外用製剤の製造方法は特に限定されず、外用製剤の形態に応じて、当 業者に周知'慣用の製造方法を採用することができる。本発明の外用製剤の製造に あたっては、 1種又は 2種以上の製剤用添加物を用いることができる力 それらの必 要性及び種類は、製剤の形態に応じて当業者が適宜選択することが可能である。例 えば、マクロゴールなどの水性基剤；ワセリン、流動パラフィンなどの油性基剤；ァラビ ァゴム、ゼラチン、メチルセルロース、ェチルセルロース、カルボキシメチルセルロー ス、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリアクリル 酸及びその塩、ポリビュルアルコール、ポリビュルピロリドンなどの水溶性高分子；エリ ソルビン酸、エリソルビン酸ナトリウム、ヒドロキシァ-ソール、無水亜硫酸ナトリウムな どの抗酸化剤；防腐剤;着色剤; pH調整剤などを製剤用添加物として用いることがで きるが、これらに限定されることはない。  [0016] The method for producing the external preparation of the present invention is not particularly limited, and a conventional production method known to those skilled in the art can be adopted depending on the form of the external preparation. In the production of the external preparation of the present invention, the ability to use one or more pharmaceutical additives The necessity and type thereof are appropriately selected by those skilled in the art depending on the form of the preparation. It is possible. For example, aqueous bases such as macrogol; oily bases such as petrolatum and liquid paraffin; Arabic gum, gelatin, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyacrylic acid and the like Formulated with water-soluble polymers such as salt, polybulal alcohol and polybulurpyrrolidone; antioxidants such as erythorbic acid, sodium erythorbate, hydroxy-sol, anhydrous sodium sulfite; preservatives; coloring agents; pH adjusters However, the present invention is not limited to these.
実施例  Example
[0017] 以下、実施例により本発明をさらに具体的に説明するが、本発明はこれらの実施例 に限定されるものではない。  [0017] Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.
〔実施例 1〕 テープ剤  [Example 1] Tape
(重量％)  (% By weight)
スチレン イソプレン スチレンブロック共重合体 21. 5  Styrene Isoprene Styrene block copolymer 21.5
水素添カ卩ロジングリセリンエステル 22. 5  Hydrogenated carbazine glycerin ester 25.5
流動パラフィン 39. 5 ジブチルヒドロキシトルエン 1. 0 Liquid paraffin 39.5 Dibutylhydroxytoluene 1.0
マクロゴール 10. 0  Macrogol 10.0
フェルビナク 2. 5  Felbinac 2.5
2—メチルー 3—（1 メンチルォキシ）プロパン —ジオール  2-Methyl-3- (1-menthyloxy) propane-diol
上記成分をニーダ一にて混合し、剥離処理の施されたポリエステルフィルムに展延 し、ポリエステル織布で覆い圧着転写し、テープ剤とした。  The above components were mixed in a kneader, spread on a polyester film that had been subjected to a release treatment, covered with a polyester woven fabric, and transferred by pressure bonding to obtain a tape agent.
[0018] 〔実施例 2〕 テープ剤  [Example 2] Tape agent
(重量％)  (% By weight)
スチレン イソプレン スチレンブロック共重合体 21. 0  Styrene Isoprene Styrene block copolymer 21.0
水素添カ卩ロジングリセリンエステル 22. 0  Hydrogenated carbazine glycerin ester 22.0
流動パラフィン 38. 5  Liquid paraffin 38.5
ジブチルヒドロキシトルエン 1. 0  Dibutylhydroxytoluene 1.0
マクロゴーノレ 10. 0  Macrogonore 10.0
ジクロフェナクナトリウム 2. 5  Diclofenac sodium 2.5
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 5. 0  2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 5.0
上記成分をニーダ一にて混合し、剥離処理の施されたポリエステルフィルムに展延 し、ポリエステル織布で覆い圧着転写し、テープ剤とした。  The above components were mixed in a kneader, spread on a polyester film that had been subjected to a release treatment, covered with a polyester woven fabric, and transferred by pressure bonding to obtain a tape agent.
[0019] 〔実施例 3〕 テープ剤  [Example 3] Tape agent
(重量％)  (% By weight)
スチレン イソプレン スチレンブロック共重合体 22. 0  Styrene Isoprene Styrene block copolymer 22.0
水素添カ卩ロジングリセリンエステル 24. 0  Hydrogenated cellulose glycerin ester 24. 0
流動パラフィン 39. 5  Liquid paraffin 39.5
ジブチルヒドロキシトルエン 1. 0  Dibutylhydroxytoluene 1.0
マクロゴーノレ 10. 0  Macrogonore 10.0
塩酸エペリゾン 0. 5  Eperisone hydrochloride 0.5
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 3. 0  2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 3.0
上記成分をニーダ一にて混合し、剥離処理の施されたポリエステルフィルムに展延 し、ポリエステル織布で覆い圧着転写し、テープ剤とした。 [0020] 〔実施例 4〕 パップ剤 The above components were mixed in a kneader, spread on a polyester film that had been subjected to a release treatment, covered with a polyester woven fabric, and transferred by pressure bonding to obtain a tape agent. [0020] [Example 4] Cataplasm
(重量％)  (% By weight)
サリチル酸グリコール 1. 0  Glycosalicylate 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 0. 3 ポリアクリル酸ナトリウム 5. 0  2-Methyl-3- (1 menthyloxy) propane 1,2 diol 0.3 Sodium polyacrylate 5.0
カノレボキシビニノレポリマー 1. 0  Canoleboxini Vinyle Polymer 1.0
力ノレメロースナトリウム 1. 5  Force Noremelose Sodium 1.5
軽質無水ケィ酸 2. 0  Light anhydrous anhydrous 2.0
セスキ才レイン酸ソノレビタン 0. 5  Sesuki-born Sonorebitan Leinate 0.5
乾燥水酸ィ匕アルミニウムゲル 0. 1  Dry hydroxyaluminum gel 0.1
乳酸 1. 0  Lactic acid 1.0
濃グリセリン 30. 0  Concentrated glycerin 30. 0
精製水 残量  Purified water remaining
上記成分をニーダ一にて混合し、これを不織布上に均一に展延して、剥離ライナ 一としてのポリエステルフィルムで圧着し、ノ ップ剤とした。  The above components were mixed with a kneader, spread evenly on a non-woven fabric, and pressure-bonded with a polyester film as a release liner to obtain a knocking agent.
[0021] 〔実施例 5〕 ゲル軟膏剤 [Example 5] Gel ointment
(重量％)  (% By weight)
カノレボキシビニノレポリマー 1. 5  Canoleboxyvininole polymer 1.5
卜ジエタノールァミン 2. 0  卜 Diethanolamine 2.0
エタノール 40. 0  Ethanol 40. 0
ケトプロフェン 3. 0  Ketoprofen 3.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 0. 5 精製水 残量  2—Methyl-3— (1 menthyloxy) propane 1, 2 diol 0.5 Purified water Remaining
上記成分をミキサーにて混和し、ゲル軟膏剤とした。  The above components were mixed with a mixer to obtain a gel ointment.
[0022] 〔実施例 6〕 ゲル軟膏剤 [Example 6] Gel ointment
(重量％)  (% By weight)
カノレボキシビニノレポリマー 1. 5  Canoleboxyvininole polymer 1.5
卜ジエタノールァミン 2. 0 エタノーノレ 40. 0 ケトプロフェン 3. 0 卜 Diethanolamine 2.0 Etanolore 40. 0 Ketoprofen 3.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 1. 0 精製水 残量  2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 1.0 Purified water Remaining
上記成分をミキサーにて混和し、ゲル軟膏剤とした。  The above components were mixed with a mixer to obtain a gel ointment.
[0023] 〔実施例 7〕 ゲル軟膏剤 [Example 7] Gel ointment
(重量％) カルボキシビ二ルポリマー 1. 5 卜リエタノールァミン 2. 0 ヱタノ一ノレ 40. 0 ケトプロフェン 3. 0  (% By weight) Carboxyvinyl polymer 1.5 ヱ Liethanolamine 2. 0 ヱ Tanoinole 40. 0 Ketoprofen 3.0
2—メチルー 3— (1—メンチルォキシ）プロパン一 1, 2 ジオール 2. 0 精製水 残量  2-Methyl-3- (1-Mentyloxy) propane-1,2, diol 2.0 Purified water Remaining
上記成分をミキサーにて混和し、ゲル軟膏剤とした。  The above components were mixed with a mixer to obtain a gel ointment.
[0024] 〔実施例 8〕 ゲル軟膏剤 [Example 8] Gel ointment
(重量％) カルボキシビ二ルポリマー 1. 5 卜!;エタノールァミン 2. 0 エタノーノレ 40. 0 インドメタシン 1. 0  (Wt%) Carboxyvinyl polymer 1.5 卜!; Ethanolamine 2.0 Ethanol 40. 0 Indomethacin 1.0
2—メチルー 3— (1—メンチルォキシ）プロパン一 1, 2 ジオール 0. 5 精製水 残量  2-Methyl-3- (1-Mentyloxy) propane-1,2-diol 0.5 Purified water Remaining
上記成分をミキサーにて混和し、ゲル軟膏剤とした。  The above components were mixed with a mixer to obtain a gel ointment.
[0025] 〔実施例 9〕 ゲル軟膏剤 [Example 9] Gel ointment
(重量％) カノレボキシビニノレポリマー 1. 5 トリエタノーノレアミン 2. 0 エタノーノレ 40. 0 インドメタシン 1. 0 (Wt%) Canoleboxyvininole polymer 1.5 Trienanolamine 2. 0 Ethanol 40.0 Indomethacin 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 1. 0 精製水 残量  2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 1.0 Purified water Remaining
上記成分をミキサーにて混和し、ゲル軟膏剤とした。  The above components were mixed with a mixer to obtain a gel ointment.
[0026] 〔実施例 10〕 ゲル軟膏剤 [Example 10] Gel ointment
(重量％) カノレボキシビニノレポリマー 1. 5 卜ジエタノールァミン 2. 0 エタノール 40. 0 インドメタシン 1. 0  (% By weight) Canoleboxyvininole polymer 1.5 卜 Diethanolamine 2. 0 Ethanol 40. 0 Indomethacin 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 2. 0 精製水 残量  2—Methyl-3— (1 menthyloxy) propane 1, 2 diol 2.0 Purified water remaining
上記成分をミキサーにて混和し、ゲル軟膏剤とした。  The above components were mixed with a mixer to obtain a gel ointment.
[0027] 〔実施例 11〕 軟膏剤 [Example 11] Ointment
(重量％) ポジエチレングジ 一ノレ 400 45. 5 ポジエチレングジ 一ノレ 4000 45. 5 ミリスチン酸イソプロピノレ 5. 0 ピロキシカム 1. 0  (% By weight) Posiethylene gauze Monore 400 45.5 Posiethylene glue Monore 4000 45.5 Isopropinole myristate 5.0 Piroxicam 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 3. 0 上記成分をミキサーにて混和し、軟膏剤とした。  2-Methyl-3- (1 menthoxy) propane 1,2 diol 3.0 The above ingredients were mixed in a mixer to obtain an ointment.
[0028] 〔実施例 12〕 軟膏剤 [Example 12] Ointment
(重量％) ポジエチレングジ 一ノレ 400 45. 5 ポジエチレングジ 一ノレ 4000 45. 5 ミリスチン酸イソプロピノレ 5. 0 メロキシカム 1. 0  (Wt%) Posiethylene Gujinore 400 45.5 Posiethylene Gujinore 4000 45.5 Isopropinole myristate 5.0 Meloxicam 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 3. 0 上記成分をミキサーにて混和し、軟膏剤とした。 2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 3.0 The above ingredients were mixed with a mixer to obtain an ointment.
[0029] 〔実施例 13〕 クリーム剤  [Example 13] Cream
(重量％) ペンタスルホン酸デカグリセリル 1. 0 ステアリン酸 3. 5 ベへ-ノレァノレコーノレ 2. 5 パルミチン酸セチル 3. 0 スクヮラン 8. 0 トリ 2 ェチルへキサン酸グリセリル 8. 0 (% By weight) Decaglyceryl pentasulfonate 1.0 Stearic acid 3.5 Benorenoreconole 2.5 Cetyl palmitate 3. 0 Scranane 8.0 Glyceryl triethyl hexylate 8.0
1, 3 ブチレングリコーノレ 3. 0 グリセリン 3. 0 1, 3 Butylene glyconole 3. 0 Glycerin 3.0
フノレノレビプロフェン 1. 0 Funore Norebiprofen 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 3. 0 精製水 残量 2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 3.0 Purified water remaining
上記成分をミキサーにて混和し、クリーム剤とした。  The above ingredients were mixed with a mixer to obtain a cream.
[0030] 〔実施例 14〕 クリーム剤 [Example 14] Cream
(重量％) 白色ワセリン 25. 0 ステアリルアルコール 22. 0 プロピレングリコール 12. 0 ラウリル硫酸ナトリウム 1. 5 フノレノレビプロフェン 1. 0 (Wt%) White petrolatum 25. 0 Stearyl alcohol 22.0 Propylene glycol 12.0 Sodium lauryl sulfate 1.5 Funolerebiprofen 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 3. 0 精製水 残量 2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 3.0 Purified water remaining
上記成分をミキサーにて混和し、クリーム剤とした。  The above ingredients were mixed with a mixer to obtain a cream.
[0031] 〔実施例 15〕 ローション剤 [0031] [Example 15] Lotion
(重量％) エタノーノレ 50. 0 1, 3 ブチレングリコー/レ 5. 0 (Wt%) Ethanore 50. 0 1, 3 Butylene Glyco / Le 5.0
塩化カルプロニゥム 1. 0  Carpronium chloride 1.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 0. 1 精製水 残量  2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 0.1 Purified water remaining
上記成分をミキサーにて混和し、ローション剤とした。  The above ingredients were mixed with a mixer to obtain a lotion agent.
[0032] 〔実施例 16〕 ローション剤 [Example 16] Lotion
(重量％)  (% By weight)
エタノーノレ 50. 0  Ethanore 50. 0
プロピレングリコール 5. 0  Propylene glycol 5.0
ミノキシジノレ 1. 0  Minoxidinore 1. 0
2—メチル 3— (1—メンチルォキシ）プロパン一 1， 2 ジオール 0. 3 精製水 残量  2-Methyl 3- (1-Mentyloxy) propane 1,2 diol 0.3 Purified water Remaining
上記成分をミキサーにて混和し、ローション剤とした。  The above ingredients were mixed with a mixer to obtain a lotion agent.
[0033] 〔実施例 17〕 リニメント剤 [Example 17] Liniment agent
(重量％)  (% By weight)
エタノール 45. 0  Ethanol 45.0
濃グリセリン 2. 5  Concentrated glycerin 2.5
フェルビナク 3. 0  Felbinac 3.0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 0. 3 精製水 残量  2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 0.3 Purified water remaining
上記成分をミキサーにて混和し、リニメント剤とした。また、同様に操作し、スプレー 用容器に充填し、ノンガススプレー剤とした。  The above components were mixed with a mixer to obtain a liniment. In addition, the same operation was performed, and the container for spraying was filled into a non-gas spray.
[0034] 〔実施例 18〕 エアゾール剤 [Example 18] Aerosol agent
(重量％)  (% By weight)
エタノーノレ 55. 0  Ethanore 55. 0
クロタミトン 5. 0  Crotamiton 5.0
インドメタシン 1. 0  Indomethacin 1.0
2—メチル 3— (1—メンチルォキシ）プロパン一 1， 2 ジオール 0. 3 精製水 残量 2-Methyl 3- (1-Mentyloxy) propane 1,2 diol 0.3 Purified water remaining
上記成分をミキサーにて混和し、耐圧容器に入れ、ジメチルエーテルを充填し、ェ ァゾール剤とした。  The above components were mixed in a mixer, placed in a pressure vessel, filled with dimethyl ether, and used as an aerosol agent.
[0035] 〔実施例 19〕 スティック剤  [Example 19] Stick agent
(重量％)  (% By weight)
ステアリン酸ナトリウム 7. 0  Sodium stearate 7.0
イソプロパノーノレ 5. 0  Isopropanol 5
1, 3 ブチレングリコーノレ 65. 0  1, 3 Butylene Gliconole 65.0
フェルピナク 1. 0  Ferpinac 1. 0
ポリオキシエチレン硬化ヒマシ油 1. 0  Polyoxyethylene hydrogenated castor oil 1. 0
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオール 7. 0 精製水 残量  2-Methyl-3- (1 menthyloxy) propane 1, 2 diol 7.0 Purified water remaining
上記成分をミキサーにて加熱しながら混和し、均一な溶液とし、これを冷却し、固化 させ、スティック剤とした。  The above components were mixed while heating with a mixer to obtain a uniform solution, which was cooled and solidified to obtain a stick agent.
[0036] 〔比較例 1〕 ゲル軟膏剤 [Comparative Example 1] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールを配合しない以外 は、実施例 5と全く同様の配合及び製造法でゲル軟膏剤を調製した。  A gel ointment was prepared by the same formulation and production method as in Example 5 except that 2-methyl-3- (1 menthyloxy) propane 1,2 diol was not blended.
〔比較例 2〕 ゲル軟膏剤  [Comparative Example 2] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの替わりに 1ーメン トールを配合した以外は、実施例 5と全く同様の配合及び製造法でゲル軟膏剤を調 製した。  A gel ointment was prepared by the same formulation and production method as in Example 5, except that 1-menthol was blended instead of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
〔比較例 3〕 ゲル軟膏剤  [Comparative Example 3] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの替わりに 1ーメン トールを配合した以外は、実施例 6と全く同様の配合及び製造法でゲル軟膏剤を調 製した。  A gel ointment was prepared by the same formulation and production method as in Example 6 except that 1-menthol was blended in place of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
[0037] 〔比較例 4〕 ゲル軟膏剤  [0037] [Comparative Example 4] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの替わりに 1ーメン トールを配合した以外は、実施例 7と全く同様の配合及び製造法でゲル軟膏剤を調 製した。 A gel ointment was prepared using the same formulation and production method as in Example 7, except that 1-menthol was added instead of 2-methyl-3- (1 menthyloxy) propane 1,2 diol. Made.
〔比較例 5〕 ゲル軟膏剤  [Comparative Example 5] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールを配合しない以外 は、実施例 8と全く同様の配合及び製造法でゲル軟膏剤を調製した。  A gel ointment was prepared by the same formulation and production method as in Example 8, except that 2-methyl-3- (1 menthyloxy) propane 1,2 diol was not blended.
〔比較例 6〕 ゲル軟膏剤  [Comparative Example 6] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの替わりに 1ーメン トールを配合した以外は、実施例 8と全く同様の配合及び製造法でゲル軟膏剤を調 製した。  A gel ointment was prepared by the same formulation and production method as in Example 8, except that 1-menthol was blended in place of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
[0038] 〔比較例 7〕 ゲル軟膏剤  [Comparative Example 7] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの替わりに 1ーメン トールを配合した以外は、実施例 9と全く同様の配合及び製造法でゲル軟膏剤を調 製した。  A gel ointment was prepared by the same formulation and production method as in Example 9, except that 1-menthol was blended in place of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
〔比較例 8〕 ゲル軟膏剤  [Comparative Example 8] Gel ointment
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの替わりに 1ーメン トールを配合した以外は、実施例 10と全く同様の配合及び製造法でゲル軟膏剤を 調製した。  A gel ointment was prepared by the same formulation and production method as in Example 10, except that 1-menthol was blended instead of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
〔比較例 9〕 パップ剤  [Comparative Example 9] Cataplasm
2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールの替わりに 1ーメン トールを配合した以外は、実施例 4と全く同様の配合及び製造法でパップ剤を調製し た。  A cataplasm was prepared by the same formulation and production method as in Example 4 except that 1-menthol was blended instead of 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
[0039] 〔試験例 1〕  [Test Example 1]
実施例 5〜10のゲル軟膏剤及び比較例 1〜8のゲル軟膏剤につ!、て、ヘアレスマ ウス皮膚透過試験を行った。試験方法はフランツ型セルにヘアレスマウス摘出皮膚 を装着して、ドナーセルに製剤 0. 5mLを、レシーバーセルにリン酸緩衝生理食塩液 4mLを適用した。実験は 32°Cで行った。一定時間ごとに、レシーバー溶液の一部を 採取し、レシーバー側に透過した薬物量を、 HPLCで定量した。試験結果について ケトプロフェンの透過速度及びラグタイムを表 1に、インドメタシンの透過速度及びラ グタイムを表 2に示す。 [0040] [表 1] The gel ointment of Examples 5 to 10 and the gel ointment of Comparative Examples 1 to 8 were subjected to a hairless mouse skin permeation test. In the test method, hairless mouse-extracted skin was attached to a Franz-type cell, 0.5 mL of the preparation was applied to the donor cell, and 4 mL of phosphate buffered saline was applied to the receiver cell. The experiment was performed at 32 ° C. A portion of the receiver solution was collected at regular intervals, and the amount of drug that permeated the receiver was quantified by HPLC. Test results Table 1 shows the permeation rate and lag time of ketoprofen, and Table 2 shows the permeation rate and lag time of indomethacin. [0040] [Table 1]
Figure imgf000016_0001
Figure imgf000016_0001
[0041] 薬効成分をケトプロフェンとした場合、清涼化剤を配合していない比較例 1の透過 速度 114. 8 ( gZcm2Zhr)に対して、清涼化剤に 2—メチル 3— (1—メンチルォ キシ）プロパン 1, 2 ジオールをそれぞれ 0. 5重量％、 1. 0重量％、 2. 0重量％ 配合した実施例 5、実施例 6、実施例 7における透過速度の増加率は 30%、 51%、 8 4%であり、ほとんど経皮吸収速度には影響を及ぼさな力つた。 [0041] When ketoprofen is used as the medicinal component, the permeation rate of 14.8 (gZcm 2 Zhr) in Comparative Example 1 in which no refreshing agent is added is compared with 2-methyl 3- (1-menthylo) as the refreshing agent. In Example 5, Example 6, and Example 7 in which 0.5%, 1.0%, and 2.0% by weight of xy) propane 1,2 diol were blended, the rate of increase in permeation rate was 30%, 51 %, 84%, almost no influence on the transdermal absorption rate.
一方、清涼化剤に 1 メントールを同様に配合した比較例 2、比較例 3、比較例 4に おける透過速度の増加率は、 70%、 284%、 373%と、経皮吸収速度に大きく影響 した。  On the other hand, the rate of increase in permeation rate in Comparative Example 2, Comparative Example 3, and Comparative Example 4 in which 1 menthol was similarly blended with the refreshing agent was 70%, 284%, and 373%, which greatly affected the transdermal absorption rate. did.
[0042] [表 2]  [0042] [Table 2]
Figure imgf000016_0002
Figure imgf000016_0002
[0043] 薬効成分をインドメタシンとした場合、清涼化剤を配合していない比較例 5の透過 速度 16. 5 ( g/cm2/hr)に対して、清涼化剤に 2—メチル 3— (1—メンチルォ キシ）プロパン 1, 2 ジオールをそれぞれ 0. 5重量％、 1. 0重量％、 2. 0重量％ 配合した実施例 8、実施例 9、実施例 10における透過速度の増加率は 8%、 61%、 2 20%と、ほとんど経皮吸収速度には影響を及ぼさな力つた。 一方、清涼化剤に 1 メントールを同様に配合した比較例 6、比較例 7、比較例 8に おける透過速度の増加率は、 212%、 900%、 985%と、経皮吸収速度に大きく影響 した。 [0043] When the medicinal component is indomethacin, the permeation rate of Comparative Example 5 in which no refreshing agent is blended is 16.5 (g / cm 2 / hr), whereas the refreshing agent is 2-methyl 3— ( The rate of increase in permeation rate in Examples 8, 9, and 10 containing 1-menthoxy) propane 1,2 diol was 0.5% by weight, 1.0% by weight, and 2.0% by weight, respectively. %, 61%, and 2 20%, almost no influence on the transdermal absorption rate. On the other hand, the rate of increase in permeation rate in Comparative Example 6, Comparative Example 7, and Comparative Example 8 in which 1 menthol was blended in the same manner as the refreshing agent was 212%, 900%, and 985%, greatly affecting the transdermal absorption rate. did.
[0044] 〔試験例 2〕  [0044] [Test Example 2]
実施例 4のパップ剤及び比較例 9のパップ剤について、官能評価試験を行った。試 験方法はパップ剤を肩に貼付し、その生理学的清涼効果とにお!/ヽを比較検討した。 表 3に示す判定項目で試験した。被験者の回答した点数を合計して、平均値を示し た官能評価結果を表 4に示す。  A sensory evaluation test was performed on the cataplasm of Example 4 and the cataplasm of Comparative Example 9. In the test method, a poultice was applied to the shoulder, and the physiological refreshing effect was compared with the odor! Tests were conducted using the judgment items shown in Table 3. Table 4 shows the sensory evaluation results, which are the average of the scores that the subjects answered.
[0045] [表 3] [0045] [Table 3]
Figure imgf000017_0001
Figure imgf000017_0001
[0046] [表 4]
Figure imgf000017_0002
[0046] [Table 4]
Figure imgf000017_0002
[0047] 以上の結果から明らかなように、清涼化剤として 2—メチルー 3—（1 メンチルォキ シ)プロパン— 1, 2 ジオールを配合した実施例 4の外用製剤は、 1 メントールを配 合した比較例 9に対して、清涼感の強さは同等に保ちながらも、においの強さは約 6 分の 1となった。  [0047] As is apparent from the above results, the external preparation of Example 4 containing 2-methyl-3- (1 menthyloxy) propane-1,2 diol as a refreshing agent was compared with 1 menthol. Compared to Example 9, while maintaining the same refreshing intensity, the odor intensity was about 1/6.
産業上の利用可能性  Industrial applicability
[0048] 本発明の外用製剤は、ハツ力臭などの刺激臭が抑制され、かつ薬効成分の経皮吸 収速度に実質的に影響を与えない清涼化剤を含む外用製剤であり、貼付剤などとし て好適に使用できる。 [0048] The external preparation of the present invention is an external preparation containing a refreshing agent that suppresses an irritating odor such as a heart odor and does not substantially affect the percutaneous absorption rate of a medicinal ingredient. It can be suitably used as, for example.

Claims

請求の範囲 [1] 外用製剤であって、 Claims [1] An external preparation,
(1)薬効成分、及び  (1) medicinal ingredients, and
(2)ハツ力臭が抑制されており、かつ上記薬効成分の経皮吸収速度に実質的に影響 を与えな!/ヽ清涼化剤を含む外用製剤。  (2) An external preparation containing a refreshing agent that suppresses the heart odor and does not substantially affect the transdermal absorption rate of the above-mentioned medicinal ingredients!
[2] 上記清涼ィ匕剤が 2—メチル—3— (1—メンチルォキシ)プロパン— 1, 2 ジオール又 はその誘導体である請求の範囲第 1項に記載の外用製剤。  [2] The external preparation according to claim 1, wherein the refreshing agent is 2-methyl-3- (1-menthyloxy) propane-1,2 diol or a derivative thereof.
[3] 上記清涼化剤が 2—メチルー 3—（1 メンチルォキシ）プロパン 1, 2 ジオールで ある請求の範囲第 1項に記載の外用製剤。 [3] The preparation for external use according to claim 1, wherein the refreshing agent is 2-methyl-3- (1-menthyloxy) propane 1,2 diol.
[4] 上記清涼化剤の配合量が、外用製剤の組成物全重量に対して 0. 0001〜20重量[4] The amount of the refreshing agent is 0.0001 to 20% by weight based on the total weight of the composition for external use.
%である請求の範囲第 1項ないし第 3項のいずれか 1項に記載の外用製剤。 The external preparation according to any one of claims 1 to 3, wherein the external preparation is%.
[5] 薬効成分が、非ステロイド系抗炎症剤及びその誘導体、骨格筋弛緩剤、及び血管拡 張剤からなる群力 選ばれる 1又は 2以上の薬効成分である請求の範囲第 1項ないし 第 4項のいずれか 1項に記載の外用製剤。 [5] The medicinal ingredient is one or more medicinal ingredients selected from the group consisting of non-steroidal anti-inflammatory drugs and derivatives thereof, skeletal muscle relaxants, and vasodilators. 5. The external preparation according to any one of items 4.
[6] 貼付剤、固形製剤、半固形製剤、液剤、又はスプレー剤の形態である請求の範囲第[6] Claims in the form of a patch, solid preparation, semi-solid preparation, solution, or spray
1項な 、し第 5項の 、ずれ力 1項に記載の外用製剤。 The topical preparation according to Item 1, No. 5, No. 5 and Displacement Force 1.
PCT/JP2005/021754 2004-11-29 2005-11-28 Medicinal preparation for external use WO2006057375A1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013184936A (en) * 2012-03-08 2013-09-19 Naris Cosmetics Co Ltd Cosmetic
CN109589281A (en) * 2018-12-25 2019-04-09 澳宝化妆品（惠州）有限公司 A kind of clothing cool spray agent and preparation method thereof of the leaf oil containing peppermint

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09217083A (en) * 1996-02-08 1997-08-19 Takasago Internatl Corp Improver for refreshing feeling
JP2002179517A (en) * 2000-12-12 2002-06-26 Takasago Internatl Corp Thermesthesia composition
WO2003074622A1 (en) * 2002-03-01 2003-09-12 Takasago International Corporation Refrigerant compositions, refrigerant auxiliary compositions and uses thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09217083A (en) * 1996-02-08 1997-08-19 Takasago Internatl Corp Improver for refreshing feeling
JP2002179517A (en) * 2000-12-12 2002-06-26 Takasago Internatl Corp Thermesthesia composition
WO2003074622A1 (en) * 2002-03-01 2003-09-12 Takasago International Corporation Refrigerant compositions, refrigerant auxiliary compositions and uses thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013184936A (en) * 2012-03-08 2013-09-19 Naris Cosmetics Co Ltd Cosmetic
CN109589281A (en) * 2018-12-25 2019-04-09 澳宝化妆品（惠州）有限公司 A kind of clothing cool spray agent and preparation method thereof of the leaf oil containing peppermint

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