KR100340100B1 - Contents for the scabicidal and antipruritic agent in a form of plaster and transdermal delivery system - Google Patents
Contents for the scabicidal and antipruritic agent in a form of plaster and transdermal delivery system Download PDFInfo
- Publication number
- KR100340100B1 KR100340100B1 KR1019990029673A KR19990029673A KR100340100B1 KR 100340100 B1 KR100340100 B1 KR 100340100B1 KR 1019990029673 A KR1019990029673 A KR 1019990029673A KR 19990029673 A KR19990029673 A KR 19990029673A KR 100340100 B1 KR100340100 B1 KR 100340100B1
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- skin
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- 239000003908 antipruritic agent Substances 0.000 title 1
- 239000011505 plaster Substances 0.000 title 1
- 230000037317 transdermal delivery Effects 0.000 title 1
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 238000010521 absorption reaction Methods 0.000 claims abstract description 12
- 239000000853 adhesive Substances 0.000 claims abstract description 6
- 230000001070 adhesive effect Effects 0.000 claims abstract description 6
- 239000010410 layer Substances 0.000 claims description 55
- 229940079593 drug Drugs 0.000 claims description 45
- 239000003814 drug Substances 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 44
- -1 dl-campa Chemical compound 0.000 claims description 20
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 18
- 229960000520 diphenhydramine Drugs 0.000 claims description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 239000003655 absorption accelerator Substances 0.000 claims description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
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Classifications
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- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 항히스타민제, 진양제 및 항염증제를 함유하는 진양첩부제에 관한 것이다. 본 발명에 따른 진양첩부제는 점착력이 우수하고 떼어내기 쉽고 높은 흡수율을 보이며, 기존의 피부적용제제가 갖고 있는 2차 감염, 끈적거림 등의 문제점도 해결한 우수한 피부적용제제이다.The present invention relates to a yangyang patch containing antihistamines, yangyang and anti-inflammatory agents. The yangyang patch according to the present invention is an excellent skin applying agent that is excellent in adhesive strength, easy to peel off and exhibits a high absorption rate, and also solves problems such as secondary infection and stickiness of existing skin applying agents.
Description
본 발명은 항히스타민제, 진양제 및 항염증제를 함유하는 진양첩부제에 관한 것이다. 피부질환은 찰과상 등 다양한 원인으로 발생하는데 특히, 여름철에는 벌레에 의한 교상, 습진, 두드러기, 땀띠 그리고 각종 원인에 의한 피부가려움증 및 피부염 질환이 발생하기 쉽다. 이들 증상에 사용되는 국소적용 약제 조성물로서 연고제, 크림제, 액제, 산제, 겔제, 현탁제, 페이스트제, 팅크제 등의 제제가 알려져 있다.The present invention relates to a yangyang patch containing antihistamines, yangyang and anti-inflammatory agents. Skin diseases are caused by various causes such as abrasions. Especially, in summer, insect bites, eczema, urticaria, sweat bands and various skin itching and dermatitis diseases are likely to occur. As topical pharmaceutical compositions for use in these symptoms, preparations such as ointments, creams, solutions, powders, gels, suspensions, pastes and tinctures are known.
그러나 이들 약제 조성물을 환부에 적용시 피부에 잔존하는 약제 조성물이 피복에 달라 붙거나 이로 인한 약효 성분의 불완전한 흡수 및 일상활동의 곤란함을 일으키고 또한 약제를 도포한 환부를 긁어서 상처가 생길 경우는 외부로부터 2차 감염이 될 수 있는 문제점이 있다. 앞에서 언급한 약물의 피부투과성을 높이기 위한 예는 다음과 같다. 대한민국 특허공개 99-014956은 피부적용을 한 약용팩제로약물을 적용한 후 약간의 시간이 경과해야만 제제형태를 유지하므로 사용상 불편한 감이 있다. 일본특허 JP특개소 60-188314는 크로타미톤을 유효성분으로 2∼15중량%의 함량이 포함된 단순 플라스타로 적용하였고 일본특허 JP특개소 60-188315는 글리실레틴산류를 유효성분으로하여 흡수촉진제의 사용이 적절하지 못하여 흡수가 빠르지 않았으며, 일본특허 JP특개평 9-110680은 진양, 살균 및 보습성분을 배합하여 건조 피부질환의 치료에 쓰이는 첩부제로 주로 피부염에 적용하고 있다.However, when the pharmaceutical composition is applied to the affected part, the remaining pharmaceutical composition on the skin adheres to the coating, thereby causing incomplete absorption of the active ingredient and difficulty in daily activities, and also when the wound is caused by scratching the affected area where the drug is applied. There is a problem that can be a secondary infection from. Examples to improve the skin permeability of the aforementioned drugs are as follows. Republic of Korea Patent Publication 99-014956 is a inconvenience in use because it maintains the formulation only after a certain time after applying the drug as a medicinal pack applied to the skin. Japanese Patent JP Patent Application No. 60-188314 was applied as a simple platter containing 2 to 15% by weight of crotamiton as an active ingredient, and Japanese Patent JP Patent Application No. 60-188315 was selected from glycyletin acids as an active ingredient. Absorption was not fast due to the inadequate use of absorption accelerators. Japanese Patent Application Publication No. 9-110680 is a patch used in the treatment of dry skin diseases by combining yangyang, bactericidal and moisturizing ingredients, and is mainly applied to dermatitis.
따라서, 본 발명은 기존의 피부적용제제의 문제점을 해결하면서도 벌레물린 부위에 접촉을 함으로 순간적으로 가려움을 억제시키는 방법으로 가려움의 고통에서 해방과 동시에 가려움으로 인한 피부 긁힘으로 인한 피부손상 및 염증으로 인한 제 2의 감염을 예방하고자 한다. 높은 흡수율과 사용이 편리하고 약효지속시간을 오래 유지할 수 있는 경피흡수제제의 개발을 목적으로 한다.Therefore, the present invention solves the problem of the existing skin application agent by the method of suppressing the itching instantaneously by contacting the insect bite site, due to the skin damage and inflammation due to skin scratching due to itching at the same time as the release of itching To prevent a second infection. The purpose of this study is to develop a transdermal absorbent which has high absorption rate, ease of use, and long-lasting drug efficacy.
..
본 발명은 전술한 종래의 국소적용 약제 조성물의 문제점을 해결하기 위해 관절염치료제에서 사용되는 형태인 첩부제(Plasta)의 조성물에 여름철에 다발되는 피부질환의 치료효과를 나타내는 유효성분과 다른 부성분을 혼합하여 제조한 진양 첩부제 조성물에 관한 것이다.The present invention is to solve the problems of the conventional topical pharmaceutical composition described above by mixing the active ingredient and the other sub-components showing the therapeutic effect of the skin diseases in summer to the composition of the patch (Plasta) which is a form used in the arthritis treatment agent It relates to the manufactured yangyang patch composition.
이하 본 발명을 상세히 설명하면 다음과 같다. 본 발명의 진양 첩부제 조성물은 생물학적 활성물질과 그의 염 0.5~25중량%를 함유하며, 점착성 고분자물질 25∼80중량%, 흡수촉진제 0.5∼25중량% 그리고 용해보조제 10∼40중량%를 함유하고있는 것을 특징으로 하는 경피흡수제제이다.Hereinafter, the present invention will be described in detail. Jinyang patch composition of the present invention contains 0.5 to 25% by weight of the biologically active substance and salt thereof, 25 to 80% by weight of the adhesive polymer material, 0.5 to 25% by weight of the absorption accelerator and 10 to 40% by weight of the dissolution aid Percutaneous absorption agent, characterized in that.
본 발명에 따른 진양첩부제 조성물에서 유효성분인 항히스타민제는 디펜히드라민(Diphenhydramine), 말레인산 메피라민(Mepyramine Maleate), 프로메타진(Promethazine) 등이 사용되며, 진양(국소)제는 L-멘톨(L-Menthol), dl-캄파(dl-Camphor) 및 크로타미톤(Crotamiton)이, 항염증제는 글리시레틴산(Glycyrrhetic acid), 글리콜 살리실레이트 및 메틸 살리실레이트 등이 사용되며, 이 성분은 약물저장층내에서 치료학적으로 유효한 양만큼 방출되어 경피투여가 가능하게 되는데, 함유량은 전체 약물저장층 조성에 대해 0.5~25중량%로 함유되어 그 사용량이 너무 적으면 약효가 없고 과량 첨가하면 약물저장층내에서 약물이 결정상태로 잔류하므로 침투효과가 저하됨과 함께 피부자극등의 부작용이 일어난다.Antihistamine as an active ingredient in the yangyang supernatant composition according to the present invention is used diphenhydramine (Diphenhydramine), maleic acid mepyramine (Mepyramine Maleate), promethazine (Promethazine) and the like, yangyang (local) agent L- menthol (L-Menthol), dl-Camphor and Crotamiton, and anti-inflammatory agents include glycyrrhetic acid, glycol salicylate and methyl salicylate. Is released as a therapeutically effective amount in the drug storage layer to allow transdermal administration. The content is 0.5 to 25% by weight based on the total drug storage layer composition. Since the drug remains in the crystalline state in the storage layer, the penetration effect is lowered and side effects such as skin irritation occur.
본 발명에서 사용되는 점착성 고분자물질은 의료용 약물과의 혼합이 가능한 감압성 점착성분(PSA, Pressure sensitive adhesive)으로서 수계 또는 유기용매계 물질들이 사용될 수 있다. 고분자물질은 유효성분의 운반체 역할과 함께 저장기능을 할 뿐만 아니라 다른 한편으로는 피부에 점착하여 약물저장층을 피부에 단단히 고정시키면서 피부와의 접촉면에서 좋은 확산성을 부여해주는 역할을 하게된다.The adhesive polymer material used in the present invention may be water-based or organic solvent-based materials as a pressure sensitive adhesive (PSA) that can be mixed with a medical drug. The polymer material not only functions as a carrier of the active ingredient, but also acts as a carrier of the active ingredient and, on the other hand, adheres to the skin and secures the drug storage layer firmly to the skin, thereby providing a good diffusion property in contact with the skin.
본 발명에 쓰일 수 있는 점착성고분자 물질로는 폴리이소부티렌, 천연고무, 레진, 셀룰로오스계 점착제, 폴리올프레폴리머 고분자카르복시비닐, 비닐알콜, 비닐피롤리돈, 스티렌-이소프렌-스티렌 불록 공중합체, 로진변성 말레인산 수지, 로진 에스테르, 비닐아세테이트-아크릴 공중합체, 폴리이소부틸렌, 폴리부틸아크릴레이트, 아크릴 공중합체, 히드록시프로필메틸 셀룰로오스, 히드록시에틸 셀룰로오스, 히드록시프로메틸 셀룰로오스 프탈레이트, 폴리비닐피롤리돈, 에틸렌비닐아세테이트 공중합체, 실리콘 중합체 등을 단독 또는 1종 이상을 혼합하여 적용할 수 있다.Adhesive polymer materials that can be used in the present invention include polyisobutyrene, natural rubber, resin, cellulose adhesive, polyol prepolymer polymer carboxyvinyl, vinyl alcohol, vinylpyrrolidone, styrene-isoprene-styrene block copolymer, rosin Modified maleic acid resins, rosin esters, vinyl acetate-acrylic copolymers, polyisobutylenes, polybutylacrylates, acrylic copolymers, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypromethyl cellulose phthalate, polyvinylpyrroli Pig, ethylene vinyl acetate copolymer, silicone polymer, etc. can be applied individually or in mixture of 1 or more types.
이와같은 고분자 물질은 조성물 전체에 대해 25∼80중량%로 첨가되는데, 만일 그 사용량이 25중량% 보다 적게 되면 유효성분의 운반과 저장능력이 적을 뿐만 아니라 점착성과 확산성이 떨어져서 피부 부착시 사용효율이 크게 저하되는 문제가 있으며 80중량% 보다 많게 되면 유효성분의 농도가 낮아 경피투여효과가 저하되며, 상대적으로 흡수촉진제 등의 성분함량이 적어지므로 투여효과가 나빠지는 문제가 있다.Such high molecular materials are added in an amount of 25 to 80% by weight based on the total composition. If the amount is less than 25% by weight, the transport and storage capacity of the active ingredient is not only low, but also the adhesion and diffusion are poor, and thus the efficiency of use when applying the skin There is a problem that greatly decreases and when the content is more than 80% by weight, the effect of lowering the percutaneous administration effect is lowered because the concentration of the active ingredient is lowered, and there is a problem that the administration effect is worsened because the content of the components such as absorption accelerator is relatively reduced.
본 발명에서 쓰일 수 있는 흡수촉진제는 활성물질의 피부침투를 향상시키는 기능을 수행함과 아울러 활성물질 및 점착성고분자 물질을 용해시키는 역할을 한다. 흡수촉진제로는, 예컨대 알킬렌글리콜유도체, 아자시클로알칸류, 지방산 및 그의 에스테르화물, 지방산알칸올아미드류 또는 폴리에틸렌글리콜 유도체, 계면활성제류, 알콜류, 아존류, 테르펜유 등이 사용될 수 있으며, 구체적으로는 카프린산, 올레인산, 리놀레인산, 리놀레인알콜, 올레일살콕신, 라우로일살콕신, 모노올레일-락-글리세롤, 미네랄오일, 박하유, d-리모넨, 트윈80, 스판80, 1-도데실아자시클로헵탄-2-온, 1-[(2-데실티오)에틸]아자시클로펜탄-2-온(HPE-101), 라우르디에탄올아미드, 디메틸술폭사이드, 디메틸아세트아미드, 디메틸포름아미드, 폴리에틸렌글리콜, 프로필렌글리콜, 아랄라세83, N-메틸-2-피롤리돈, 1-도데실아자시클로헵탄-2온, 트리에탄올 아민, 에탄올, 이소프로판올, 데실올레이트, 올레일 알콜, 이소프로필 리놀레이트, 부탄디올에서 1종 또는 2종 이상을 섞어서 적용할 수 있다.Absorption accelerator that can be used in the present invention serves to improve the skin penetration of the active material and also to dissolve the active material and adhesive polymer material. As the absorption accelerator, for example, alkylene glycol derivatives, azacycloalkanes, fatty acids and esters thereof, fatty acid alkanolamides or polyethylene glycol derivatives, surfactants, alcohols, azones, terpene oils and the like can be used. Examples include caprinic acid, oleic acid, linoleic acid, linolein alcohol, oleyl alkoxycin, lauroyl chalcoxin, monooleyl-lac-glycerol, mineral oil, peppermint oil, d-limonene, twin 80, span 80, 1- Dodecylazacycloheptan-2-one, 1-[(2-decylthio) ethyl] azacyclopentan-2-one (HPE-101), laudieethanolamide, dimethyl sulfoxide, dimethylacetamide, dimethylform Amide, polyethylene glycol, propylene glycol, aralla 83, N-methyl-2-pyrrolidone, 1-dodecylazacycloheptan-2one, triethanol amine, ethanol, isopropanol, decylate, oleyl alcohol, isopropyl Linoleate, butanediol One or two or more may be mixed applicable.
본 발명에 사용되는 피부흡수촉진제는 다른 흡수촉진제에 비해서 흡수촉진능력이 뛰어나므로 진양제의 피부투과력을 현저히 증가시키고 피부자극도 없어 안전하게 사용할 수 있다.The skin absorption accelerator used in the present invention has an excellent absorption promoting ability compared to other absorption accelerators, thereby significantly increasing the skin permeability of the yangyang agent and can be used safely without skin irritation.
만일, 상기 흡수촉진제가 0.5중량% 보다 적게 사용되면 첨가효과가 없으며, 25중량%보다 많게 되면 점착력이 저하되고 매트릭스의 형태 유지가 어려워진다.If the absorption accelerator is used in an amount less than 0.5% by weight, there is no additive effect. When the absorption accelerator is used in an amount of more than 25% by weight, the adhesion decreases and it becomes difficult to maintain the shape of the matrix.
한편, 본 발명의 진양첩부제 조성물에는 용해보조제로서 앞에서 예시한 유효 성분을 고농도의 용해상태로 유지시켜 줌과 동시에 흡수촉진제 역할을 하는 용매가 사용되는데, 그 사용량이 10중량% 보다 적으면 유효성분이 완전히 혼화되지 않기 때문에 투여효과가 크게 떨어지게 되고 40중량% 보다 과량은 매트릭스(matrix)의 형태를 유지시킬 수 없어 불필요하다. 이러한 용해보조제로는 예컨대 에틸아세테이트, n-헥산, 톨루엔, 프로필렌글리콜모노라우레이트, 폴리옥시에틸렌올레일에테르, 디에틸톨루아미드, 메틸알콜, 이소프로필알콜, 디메틸아세트아미드, 폴리에틸렌글리콜, 프로필렌글리콜, 폴리옥시에틸렌에스테르, 디에틸렌글리콜 모노에틸에테르 및 N-알킬 피롤리돈 또는 이들의 2종 이상 혼합액이 사용될 수 있다.On the other hand, in the yangyang supernatant composition of the present invention as a dissolving aid is used a solvent that maintains the active ingredient in a high concentration of dissolution and at the same time serves as an absorption accelerator, if the amount is less than 10% by weight of the active ingredient Since it is not completely mixed, the administration effect is greatly reduced, and an excess of more than 40% by weight is unnecessary because it cannot maintain the form of the matrix. Such dissolution aids include, for example, ethyl acetate, n-hexane, toluene, propylene glycol monolaurate, polyoxyethylene oleyl ether, diethyl toluamide, methyl alcohol, isopropyl alcohol, dimethylacetamide, polyethylene glycol, propylene glycol , Polyoxyethylene ester, diethylene glycol monoethyl ether and N-alkyl pyrrolidone or a mixture of two or more thereof may be used.
또한 본 발명은 이 첩부제 조성물로 이루어진 약물저장층(기질층)과 이 약물저장층 위에 첩부된 비투과성 지지체 및 상기 약물저장층 밑에서 박리 가능토록 부착된 박리층이 첩부제의 기본 구성 요소로 이루어진 유효약물 또는 그의 염을 함유한 진양 첩부제이다.The present invention also provides a drug storage layer (substrate layer) consisting of the patch composition, a non-permeable support attached to the drug storage layer, and a release layer attached so as to be peelable under the drug storage layer, the basic components of the patch. It is a ginseng patch containing the active drug or a salt thereof.
구체적으로, 본 발명은 항히스타민제 및 진양제 또는 그의 염을 포함하는 유효성분을 매트릭스에 함유시켜 피부부착을 통해 경피투여되도록 하는 첩부제에 관한 것으로서, 이런 투여시스템은 지지체와 박리층 사이에 끼워져 있는 약물저장층(매트릭스)으로 구성된 첩부형으로 이루어져 있다.Specifically, the present invention relates to a patch that contains an active ingredient including an antihistamine and a yangyang agent or a salt thereof in a matrix so that it can be transdermally administered through skin adhesion, wherein the administration system is sandwiched between a support and a release layer. It consists of a patch consisting of a drug storage layer (matrix).
본 발명에 따르면 약물저장층은 유효성분을 포함하여 그 유효성분의 방출속도를 조절하는 단층 또는 다층으로 이루어져 있으며, 구체적으로는 점착성 고분자 물질과 용해보조제 및 흡수촉진제를 일정 성분비로 함유하고 있다.According to the present invention, the drug storage layer is composed of a single layer or a multilayer including an active ingredient to control the release rate of the active ingredient, and specifically, contains a tacky polymer material, a dissolution aid and an absorption accelerator in a certain component ratio.
본 발명에 따른 첩부제에서 유효성분을 경피투여하기 위한 확산 매트릭스로서 실질적으로 핵심이 되는 약물저장층은 다층구조를 가질 수 있다.The drug storage layer, which is substantially the core of the diffusion matrix for transdermal administration of the active ingredient in the patch according to the present invention, may have a multilayer structure.
위와 같이 조성된 약물저장층은 비투과성 지지체위에 도포하여 건조시킴으로서 형성되는데, 필요에 따라서는 약물저장층을 다층으로 형성시킬 수 있다. 이 경우에는 제조의 편의를 위해 약물저장층을 구성하는 각층의 조성을 같게 하거나, 아니면 조성을 서로 다르게 변화시켜서 지지체에서 가장 먼 곳에 위치하는 층이 가장 빠른 피부침투가 가능하도록 하면서 차례로 중첩되게 층을 형성하여 유효성분의 확산 침투속도가 가장 늦은 경우를 지지체에 제일 가깝게 위치되도록 할 수도 있다. 이 때 다층은 3층 정도가 바람직하다.The drug storage layer formed as described above is formed by applying and drying on a non-permeable support, the drug storage layer can be formed in multiple layers as necessary. In this case, for convenience of manufacture, the composition of each layer constituting the drug storage layer is the same, or the composition is changed differently so that the layers located farthest from the support can form the layers in order while allowing the fastest skin penetration. The case where the diffusion penetration rate of the active ingredient is the slowest may be located closest to the support. At this time, about 3 layers of a multilayer are preferable.
본 발명의 첩부제에 사용될 수 있는 지지체로는 특히 한정되지 않으나 피부면에 첩부할 때에, 현저한 위화감을 발생하지 않을 정도로 유연성을 갖는 것이 바람직하고, 가령 폴리에틸렌, 폴리프로필렌, 폴리에스테르, 폴리아세트산비닐, 에틸렌-아세트산 비닐공중합체, 폴리염화비닐, 폴리우레탄 등의 플라스틱필름, 알루미늄박, 주석박 등의 금속박, 부직포, 직물, 종이 등으로 되는 단층필름이나 이들의 적층필름 등을 들수 있다. 또, 이들 지지체는 상기 기제층과의 밀착성, 접착성을 향상시키기 위하여 기제층 형성면에 코르나 방전처리나 플라즈마 처리, 산화처리 등을 시행하는 것이 바람직하다.The support that can be used in the patch of the present invention is not particularly limited, but it is preferable to have flexibility so as not to cause significant discomfort when affixing it to the skin surface, for example, polyethylene, polypropylene, polyester, polyvinyl acetate, Plastic films such as ethylene-vinyl acetate copolymer, polyvinyl chloride and polyurethane, metal foil such as aluminum foil and tin foil, single layer films made of nonwoven fabrics, textiles, paper and the like, and laminated films thereof. In addition, it is preferable that these supports be subjected to corona discharge treatment, plasma treatment, oxidation treatment or the like on the base layer formation surface in order to improve the adhesion to the base layer and the adhesion.
본 발명의 첩부제는 피부면에의 접착직전까지는 기제층의 노출면을 실리콘수지나 플루오르수지 등을 도포함으로써 이형처리를 실시한 종이나 플라스틱필름 등의 박리라이너에 의해 피복보호하는 것이 바람직하다.The patch of the present invention is preferably covered with a peeling liner such as a paper or a plastic film subjected to a release process by applying a silicone resin, a fluororesin, or the like to the exposed surface of the base layer until just before adhesion to the skin surface.
본 발명에서 비투과성 지지체 위에 약물저장층을 단층 또는 다층으로 형성시킨 후에는 박리층을 붙이는데, 박리층은 통상의 실리콘이 코팅된 폴리에틸렌필름과 같은 것이 사용되면 무난하다.In the present invention, after the drug storage layer is formed in a single layer or a multi-layer on the non-permeable support, a release layer is attached, and the release layer may be used as long as a conventional silicon coated polyethylene film is used.
이와 같이 본 발명의 첩부제를 제조공정에 따라 구체적으로 설명하면, 유효성분을 준비하여 흡수촉진제와 혼합시켜서 용액 또는 현탁액 상태로 만든다음, 이를 고분자 물질에 첨가하여 20∼30분 동안 혼합시키고 20-60분동안 정치시킨 후 기포를 제거한다. 이 혼합물을 비투과성 지지체로 준비한 투명 폴리에틸렌 필름위에 50~150㎛ 도포하여 10분간 80℃에서 건조시켜 약물저장층을 만든다음, 그 위에 박리지를 덮고 적당한 크기로 절단하여 첩부제를 얻는다.As described above, the patch of the present invention will be described in detail according to the manufacturing process. The active ingredient is prepared, mixed with an absorption accelerator, into a solution or suspension state, and then added to the polymer material for 20 to 30 minutes to be mixed. Allow to stand for 60 minutes to remove bubbles. The mixture is applied to a transparent polyethylene film prepared with a non-permeable support, 50 to 150 µm, dried at 80 ° C. for 10 minutes to form a drug storage layer, and then covered with a release paper and cut into an appropriate size to obtain a patch.
이때, 다층구조의 매트릭스 상태를 만들려면 최초 형성된 매트릭스위에 같은 방식으로 계속하여 상기 혼합물을 도포하거나 중첩시켜서 제조한다.At this time, in order to create a multi-layer matrix state, the mixture is prepared by continuously applying or superimposing the mixture on the first formed matrix in the same manner.
상기와 같이 제조된 본 발명에 따른 첩부제는 피부에 적용할 경우 박리층을 제거하고 노출된 약물저장층의 박리부위를 피부에 부착시키면 점착성 고분자물질에의해 약물저장층의 박리부위가 피부에 부착되게 되며, 그후 약물저장층 중에서 용해보조제에 용해된 상태로 고분자 물질과 혼합되어 약물저장층 전반에 분산되어 있던 유효성분은 매트릭스로부터 흡수촉진제와 함께 확산되면서 피부 각질층으로 흡수되기 시작한다.The patch according to the present invention prepared as described above is applied to the skin when the peeling layer is removed and the exposed portion of the drug storage layer is attached to the skin by the adhesive polymer material peeling site of the adhesive layer is attached to the skin After that, the active ingredient, which is mixed with the polymer material in the state of dissolving aid in the drug storage layer and dispersed throughout the drug storage layer, is diffused together with the absorption promoter from the matrix and begins to be absorbed into the stratum corneum of the skin.
이때, 흡수촉진제는 유효성분에 대한 피부를 통하여 체내 순환계로의 경피적 확산을 촉진시킨다.At this time, the absorption promoter promotes percutaneous diffusion into the circulatory system through the skin for the active ingredient.
반면에, 약물저장층의 박리부위 반대편에 위치하는 지지체에는 비투과성을 가지는 필름이 덮혀 있기 때문에 약물의 유출이나 외부로부터의 오염 등을 방지하게 된다.On the other hand, since the support having a non-permeable film is covered on the support located on the opposite side of the peeling portion of the drug storage layer to prevent leakage of the drug or contamination from the outside.
이하, 본 발명을 실시예에 의거 상세히 설명하면 다음과 같으나, 본 발명이 이들 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples.
<실시예 1><Example 1>
840mg의 디펜히드라민과 610mg의 염산디부카인과 5.34g의 카프린산을 1.6g의 N-메칠피롤리돈에 혼합 용해한 다음, 이 혼합용액을 30g의 아크릴산부틸 공중합체 고분자용액(AS-594)에 가한다음 에틸아세테이트 10g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.840 mg of diphenhydramine, 610 mg of dibucaine hydrochloride, and 5.34 g of capric acid were mixed and dissolved in 1.6 g of N-methylpyrrolidone, and then the mixed solution was mixed with 30 g of butyl acrylate copolymer polymer solution (AS-594). 10 g of ethyl acetate was added thereto, mixed for 25 minutes, and allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, the plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 2><Example 2>
1g의 디펜히드라민과 600mg의 염산디부카인에 300mg의 프로필렌글리콜과 400mg의 HPE 101을 녹인다음, 이 혼합용액을 25g의 아크릴산부틸 공중합체 고분자 용액(AS-594)에 가한다음 이소프로판올 8g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그 위에 플라스틱필름을 부착시키고 나서 3.14㎠크기로 절단하여 최종제품을 얻었다.Dissolve 300 mg of propylene glycol and 400 mg of HPE 101 in 1 g of diphenhydramine and 600 mg of dibucaine hydrochloride, add this mixed solution to 25 g of butyl acrylate copolymer polymer solution (AS-594), and add 8 g of isopropanol to 25 After mixing for a minute, the mixture was allowed to stand for 20 minutes to remove bubbles. The mixture was applied to the release paper at 50 to 150 탆, dried at 80 ° C. for 5 minutes to form a drug storage layer, and then attached to the plastic film, and cut into 3.14 cm 2 to obtain a final product.
<실시예 3><Example 3>
850mg의 말레인산 메피라민과 500mg의 폴리도카놀을 400mg의 디메틸술폭사이드와 350mg의 올레일살콕신에 녹인다음, 이 혼합용액을 26g의 셀룰로오스계 점착제를 가한다음 에틸아세테이트 7g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.Dissolve 850 mg of maleic acid methamine and 500 mg of polydocanol in 400 mg of dimethyl sulfoxide and 350 mg of oleyl oxalcoxine, add 26 g of cellulose-based adhesive, add 7 g of ethyl acetate, and mix for 25 minutes. It was left for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, the plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 4><Example 4>
1.0g의 프로메타진과 500mg의 염산디부카인에 300mg의 모노글리세리드와 300mg의 스판 80g을 녹인다음, 이 혼합용액을 24g의 비닐아세테이트-아크릴공중합체에 가한다음 에틸아세테이트 2.5g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50~150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.Dissolve 300 mg monoglyceride and 300 mg span 80 g in 1.0 g promethazine and 500 mg dibucaine hydrochloride, add this mixed solution to 24 g vinyl acetate-acrylic copolymer, add 2.5 g ethyl acetate, and mix for 25 minutes. After standing still for 20 minutes, bubbles were removed. The mixture was applied to the release sheet at 50-150 μm, dried at 80 ° C. for 5 minutes to form a drug storage layer, and then attached to the plastic film, and cut into 3.14 cm 2 to obtain a final product.
<실시예 5>Example 5
900mg의 디펜히드라민과 500mg의 염산디부카인을 400mg의 글리콜살리실레이트, 300mg의 올레일알콜,300mg의 데실올레이트에 녹인다음, 이 혼합용액을 22g의 폴리이소부티렌에 가한다음 디에틸렌글리콜모노에틸에테르 6g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.900 mg diphenhydramine and 500 mg dibucaine hydrochloride are dissolved in 400 mg glycol salicylate, 300 mg oleyl alcohol, 300 mg decylate, and this mixed solution is added to 22 g polyisobutyrene, followed by diethylene glycol. 6 g of monoethyl ether was added thereto, mixed for 25 minutes, and allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, the plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 6><Example 6>
1.0g의 디펜히드라민과 600mg의 염산디부카인에 500mg의 디메틸포름아미드와 500mg의 아랄라세 83에 녹인다음, 이 혼합용액을 24g의 히드록시에틸셀룰로오스스에 가한다음 톨루엔 5g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.Dissolve 1.0 g of diphenhydramine and 600 mg of dibucaine in 500 mg of dimethylformamide and 500 mg of Aralase 83, add this mixed solution to 24 g of hydroxyethyl cellulose, add 5 g of toluene, and mix for 25 minutes. After standing still for 20 minutes, bubbles were removed. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, the plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 7><Example 7>
1.1g의 디펜히드라민과 650mg의 염산디부카인에 600mg의 모노올레일-락-글리세롤과 200mg의 L-멘톨을 녹인다음, 이 혼합용액을 23g의 비닐알콜에 가한다음 폴리옥시에틸렌올레일에테르 6g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.Dissolve 600 mg of monooleyl-lac-glycerol and 200 mg of L-menthol in 1.1 g of diphenhydramine and 650 mg of dibucaine hydrochloride, add this mixed solution to 23 g of vinyl alcohol, and then add 6 g of polyoxyethylene oleyl ether. After adding for 25 minutes, the mixture was allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, the plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 8><Example 8>
900mg의 디펜히드라민과 350mg의 크로타미톤에 400mg의 폴리옥실 35 히드로지네이티드 카스터오일과 200mg의 dl-캄파를 녹인다음, 이 혼합용액을 20.0g의 에틸렌비닐아세테이트 공중합체에 가한다음 프로필렌글리콜모노라우레이트 5g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.After dissolving 400 mg of polyoxyl 35 hydrogenated castor oil and 200 mg of dl-campa in 900 mg of diphenhydramine and 350 mg of crotamiton, the mixed solution was added to 20.0 g of ethylene vinyl acetate copolymer, followed by propylene glycol. 5 g of monolaurate was added thereto, mixed for 25 minutes, and allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, the plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 9>Example 9
1.0g의 디펜히드라민과 400mg의 염산디부카인에 700mg의 N-메칠피롤리돈에 녹인다음, 500mg의 메칠살리실레이트와 500mg의 글리실리진산을 넣어 용해시키고, 이 혼합용액을 23g의 천연고무에 가한다음 n-헥산 6g을 가하여 25분동안 혼합한 후20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든다음, 그위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.1.0 g of diphenhydramine and 400 mg of dibucaine hydrochloride were dissolved in 700 mg of N-methylpyrrolidone, followed by dissolving 500 mg of methylsalicylate and 500 mg of glycylic acid, and dissolving the mixed solution with 23 g of natural rubber. 6 g of n-hexane was added thereto, mixed for 25 minutes, and allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, the plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 10><Example 10>
700mg의 디펜히드라민과 500mg의 L-멘톨에 2.5g의 카프린산을 녹인다음, 1.7g의 트윈 80을 넣어 용해시키고 이 혼합용액을 27g의 스티렌-이소프렌-스티렌블록 공중합체에 가한다음 디-에틸톨루아미드 12g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.Dissolve 2.5 g of capric acid in 700 mg of diphenhydramine and 500 mg of L-menthol, add 1.7 g of Tween 80 to dissolve it, and add this mixed solution to 27 g of styrene-isoprene-styrene block copolymer. 12 g of ethyltoluamide was added thereto, mixed for 25 minutes, and allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, a plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 11><Example 11>
720mg의 말레인산 메피라민과 450mg의 크로타미톤을 3.4g의 올레인산과 2.1g의 에탄올에 녹인다음, 이 혼합용액을 25g의 레진을 가한 다음, 톨루엔 15g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50~150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.After dissolving 720 mg maleic acid and 450 mg crotamiton in 3.4 g of oleic acid and 2.1 g of ethanol, 25 g of resin was added, 15 g of toluene was added, mixed for 25 minutes, and left to stand for 20 minutes. Bubbles were removed. The mixture was applied to the release paper at 50-150 μm, dried at 80 ° C. for 5 minutes to form a drug storage layer, and then adhered to a plastic film, and cut into 3.14 cm 2 to obtain a final product.
<실시예 12><Example 12>
660mg의 프로메타진과 420mg의 염산디부카인에 2.7g의 리놀레인산과 2.2g의 라우로일살콕신을 녹인 다음, 이 혼합용액을 26.5g의 비닐피롤리돈에 가한다음 디메틸아세트아미드 11.5g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.Dissolve 2.7 g of linoleic acid and 2.2 g of lauroylsalcoxin in 660 mg of promethazine and 420 mg of dibucaine hydrochloride, add this mixture to 26.5 g of vinylpyrrolidone, and add 11.5 g of dimethylacetamide to 25 After mixing for a minute, the mixture was allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, a plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 13>Example 13
750mg의 디펜히드라민과 370mg의 dl-캄파를 5.12g의 미네랄오일, 2.8g의 라우르디에탄올아미드에 녹인 다음, 이 혼합용액을 28g의 실리콘중합체에 가한다음 프로필렌글리콜 13g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.750 mg of diphenhydramine and 370 mg of dl-campa are dissolved in 5.12 g of mineral oil and 2.8 g of lauthiethanolamide, and this mixed solution is added to 28 g of silicone polymer, followed by 13 g of propylene glycol and mixed for 25 minutes. After standing still for 20 minutes, bubbles were removed. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, a plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 14><Example 14>
630mg의 말레인산 메피라민과 500mg의 염산디부카인을 4.4g의 리놀레인알콜과 3.6g의 d-리모넨에 녹인다음, 이 혼합용액을 31.5g의 로진변성말레인산수지를 가한다음, 폴리에틸렌글리콜 14g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.630 mg of maleic acid mepyramine and 500 mg of dibucaine hydrochloride are dissolved in 4.4 g of linolein alcohol and 3.6 g of d-limonene. Then, 31.5 g of rosin-modified maleic acid resin is added, and 14 g of polyethylene glycol is added to 25 After mixing for a minute, the mixture was allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, a plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 15><Example 15>
800mg의 프로메타진과 630mg의 폴리도카놀을 4.75g의 트리에탄올아민과 3.4g의 부탄디올을 녹인다음, 이 혼합용액을 32g의 히드록시프로메틸셀룰로오스프탈레이트에 가한다음 디에틸톨루아미드 17g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.800 mg of promethazine and 630 mg of polydocanol were dissolved in 4.75 g of triethanolamine and 3.4 g of butanediol, and this mixed solution was added to 32 g of hydroxypromethylcellulose phthalate, followed by 17 g of diethyltoluamide. After mixing for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, a plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 16><Example 16>
740mg의 디펜히드라민과 580mg의 폴리도카놀을 5.22g의 이소프로판올, 2.4g의 데실올레이트에 녹인 다음, 이 혼합용액을 35g의 폴리올프레폴리머 고분자카르복시비닐에 가한다음 폴리옥시에틸렌에스테르 14.5g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간 80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.740 mg of diphenhydramine and 580 mg of polydocanol are dissolved in 5.22 g of isopropanol and 2.4 g of decylate, and this mixed solution is added to 35 g of polyol prepolymer polymer carboxyvinyl, followed by 14.5 g of polyoxyethylene ester. After mixing for 25 minutes, the mixture was allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, a plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실시예 17><Example 17>
680mg의 말레인산 메피라민과 550mg의 프로메타진을 5.1g의 1-도데실아자시클로헵탄-2-온과 3.6g의 디메틸술폭사이드에 녹인 다음, 이 혼합용액을 29g의 폴리비닐피롤리돈을 가한다음, 메틸알콜 13.6g을 가하여 25분동안 혼합한 후 20분간 정치하여 기포를 제거하였다. 이 혼합물을 박리지위에 50∼150㎛로 도포하여 5분간80℃에서 건조시켜 약물저장층을 만든 다음, 그 위에 플라스틱필름을 부착시키고나서 3.14㎠크기로 절단하여 최종제품을 얻었다.680 mg of maleic acid mepyramine and 550 mg of promethazine were dissolved in 5.1 g of 1-dodecylazacycloheptan-2-one and 3.6 g of dimethyl sulfoxide, and then the mixed solution was added 29 g of polyvinylpyrrolidone. Next, 13.6 g of methyl alcohol was added thereto, mixed for 25 minutes, and allowed to stand for 20 minutes to remove bubbles. The mixture was applied at 50 to 150 μm on a release sheet and dried at 80 ° C. for 5 minutes to form a drug storage layer. Then, a plastic film was attached thereon and cut into 3.14 cm 2 to obtain a final product.
<실험예 1>Experimental Example 1
경피투여시험Transdermal administration test
상기 실시예에 따라 제조된 첩부제에 있어서 디펜히드라민, 말레인산메피라민 또는 프로메타진의 경피 플럭스를 알아보았다.The transdermal flux of diphenhydramine, maleic acid maleicamine or promethazine in the patch prepared according to the above example was examined.
체중이 약 350g인 숫컷 기니아픽의 복부털을 전기 이발기(hair clipper)로 깍은 다음 일정부위의 피부를 절취한 다음 즉시 시험에 사용하였다. 프란쯔타입의 글래스 확산기구(Franz-type diffusion cell)의 중간에 각질층 부분이 위로 향하게 피부를 설치한 후 밑부분의 공간에는 0.05M 등장 인산염 완충용액(pH 7.4)을 넣고 확산셀의 온도는 37℃를 유지시킨다. 리셉터용액(완충용액)은 일정한 속도(500rpm)로 교반하면서 확산 셀위에 상기 실시예에 따라 제조된 첩부제를 점착시키고 클립으로 고정하였다. 48시간동안 피부를 통하여 확산셀 내부로 흡수되는 디펜히드라민, 말레인산메피라민 또는 프로메타진의 양을 HPLC로 분석하여 디펜히드라민, 말레인산메피라민 또는 프로메타진의 경피플럭스를 구하였다.The abdominal hair of a male guinea pig, weighing about 350 g, was shaved with an electric hair clipper, then cut off a portion of the skin and immediately used for testing. The skin is placed in the middle of the Franz-type diffusion cell with the stratum corneum facing upwards, and then 0.05M isotonic phosphate buffer (pH 7.4) is added to the bottom space and the temperature of the diffusion cell is 37 Keep the temperature. The receptor solution (buffer solution) was agitated at a constant speed (500 rpm) and the adhesive prepared according to the above example was adhered onto the diffusion cell and fixed with a clip. The transdermal flux of diphenhydramine, maleic acid mepyramine or promethazine was obtained by analyzing the amount of diphenhydramine, maleic acid maleicamine or promethazine absorbed into the diffusion cell through the skin for 48 hours.
<조작조건><Operation Conditions>
칼 럼 : Cosmosil 5C18,(5㎛, 4mm X 150mm, Nacalai Tasque. Japan)Column: Cosmosil 5C 18, (5㎛, 4mm X 150mm, Nacalai Tasque.Japan)
이동상 : 아세트니트릴/0.01M SDS (60:40)Mobile phase: acetonitrile / 0.01M SDS (60:40)
검출기 : 자외부흡광광도계(측정파장:226nm)Detector: UV absorbance photometer (wavelength: 226 nm)
유 속 : 1.0ml/minFlow rate: 1.0ml / min
[표 1]TABLE 1
기니아픽 피부를 통한 약물의 플럭스Flux of drugs through guinea pig skin
위 표에서 보다시피 기존 일본제품 중 하나를 비교예로 경피플럭스를 비교한 결과 실시예 모두에서 3.5∼5.1배의 높은 투과율을 보였다.As shown in the above table, the transdermal flux was compared with one of the existing Japanese products as a comparative example. As a result, all of the examples showed high transmittance of 3.5 to 5.1 times.
<실험예 2>Experimental Example 2
항히스타민작용 약효실험Antihistamine Drug Activity Test
히스타민이 인체내에서 매개하는 작용은 여러가지 있는데 국소적으로는 피부의 가려움증이 대표적인 반응이다. 각종원인에 의한 알러지 혹은 염증반응에 의한 알러지 혹은 염증반응에 의한 가려움증은 히스타민수용체 길항제에 의해 비교적 잘 조절된다. 개발하려는 진양첩부제의 주성분이 디펜히드라민으로 항히스타민제이고 인체에서 느끼는 가려움증을 실험동물에서 동일하게 수치화 할 수 없기 때문에 소양증의 대표적인 원인물질인 히스타민을 피하주사하여 인위적인 혈관투과항진작용을 일으키고 이에 Evans blue를 투여하여 정량함으로서 약효를 평가하였다. Backing으로 PVC(IY-1)와 PU(IY-2)를 쓴 개발품과 기존의 일본제품중 하나를 선정하여 약효를 비교하였다.(Figure 1)Histamine mediates various effects in the human body, and itching of the skin is a typical reaction. Allergies due to various causes or itching due to inflammatory reactions are relatively well controlled by histamine receptor antagonists. Since the main ingredient of the yangyang supernatant to be developed is diphenhydramine, which is an antihistamine, and itching in the human body cannot be quantified the same in experimental animals, it is possible to subcutaneously inject the histamine, which is a representative cause of pruritus, to cause artificial vascular permeability, and thus Evans The efficacy was evaluated by quantifying by administering blue. As a backing, we selected the product using PVC (IY-1) and PU (IY-2) and one of the existing Japanese products to compare the efficacy (Figure 1).
Fig.1의 결과를 보면 정상상태(normal)에 비해 히스타민을 투여한 군(cont-rol)에서는 Evans blue 축적량이 60.4㎍/g of tissue로 정상상태에 비해 43.9% 정도 부어오른 것을 관찰할 수 있었다. 이에 대해 일본 제품은 4.23%의 치료율로 그 효과가 미미한 반면 당사에서 개발한 IY-1, IY-2는 18.2%와 17.7%로 이보다 뛰어난 치료효과를 관찰할 수 있었다. 이 중 효과가 더 우수하고 구입이 용이한 PVC 지지체를 사용하였다.In the results of Fig. 1, the concentration of Evans blue in the histamine-treated group (cont-rol) was 60.4㎍ / g of tissue, 43.9% higher than that of the normal state. . On the other hand, Japanese products had a 4.23% treatment rate, which was insignificant, while IY-1 and IY-2 developed by our company showed 18.2% and 17.7%, respectively. Among them, a PVC support having a better effect and easier to purchase was used.
<실험예 3>Experimental Example 3
60명의 남성지원자에 대하여 각 시험첩부제에 대해 10명씩 실시예에 따른 피부자극에 대해 평가하였다.Sixty male volunteers were evaluated for skin irritation according to the examples, 10 for each test patch.
시험첩부제를 지원자의 등부위에 24시간동안 부착시키고 떼어낸 후 12, 24, 48시간 경과함에 따라 발생되는 홍반, 부종 및 그 이상의 피부상태변화는 국립보건안전연구원 고시에 따라 관찰하였다. 그 주요 실시예에 따른 결과를 다음 표에 나타내었다.Changes in erythema, edema, and more skin conditions occurring after 12, 24, and 48 hours of attachment to the back of the volunteer for 24 hours and detachment were observed according to the National Institute of Health Safety. The results according to the main examples are shown in the following table.
[표 2]TABLE 2
피부자극 실험결과Skin irritation test result
0:변화없슴, 1:가벼운홍반, 2:홍반 또는 가벼운 부종0: no change, 1: light erythema, 2: erythema or mild edema
진양첩부제의 적용부위에 가벼운 홍반이 미약하게 나타났지만 24시간 후에 관찰한 피부상태는 거의 회복된 양상을 보였다.Mild erythema was weakly applied at the application site of the yangyang patch, but the skin condition observed after 24 hours was almost recovered.
본 발명에 따른 진양첩부제 조성물은 각종 벌레에 물린후 공통적으로 나타나는 가려움증, 부종, 동통 등의 증상을 개선시키는 제제로 높은 흡수율을 보이며, 기존의 피부적용제제가 갖고 있는 2차 감염, 끈적거림 등의 문제점도 해결한 우수한 피부적용제제이다.The yangyang patch composition according to the present invention shows a high absorption rate as a preparation for improving symptoms such as itching, swelling, and pain after being bitten by various insects, and secondary infection, stickiness, etc. of the existing skin application preparations. It is an excellent skin application that solves the problem.
Claims (5)
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