KR20010000254A - Non-irritating capsaicin transdermal delivery formulations - Google Patents
Non-irritating capsaicin transdermal delivery formulations Download PDFInfo
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Abstract
Description
본 발명은 외용 제제 조성물에 관한 것이고, 보다 상세하게는 유효성분으로 함유되어 있는 소수성약물의 피부흡수를 현저하게 향상시킨 외용 제제 조성물에 관한 것이다. 캡사이신(capsaicin, N-바닐릴-트란스-8-메틸-6-노넨아미드)은 고추속(capsicum) 식물의 과즙에 함유되어 있는 매운 성분으로 우수한 진통작용을 가지는 것으로 알려져 있다. 이는 관절염, 근육좌상, 염좌, 건염, 활액낭염과 같은 근골격계의 진통에 매우 효과적이다. 진통 및 진경작용을 나타내는 카파 수용체 효능제는, 아편 및 그 유도체류는 기타의 약리적효과를 가지며, 강력한 진통 및 진경작용을 나타낸다. 이는 수용체에 대한 높은 친화성을 지니기 때문에 얻어지는 효과이다. 지금까지 연구자들은 중추신경계와 말초신경계에 적어도 세 가지 이상의 아편 수용체가 있다고 발표하였다. 이들 수용체들은 독특한 약리적 양태와 기능을 가진 뮤, 델타 및 카파로 알려져 있다 ( Wood, P. L., Neuropharmacology, 21, 487-497, 1982; Simmon, E., J. Med. Res. Rev., 11, 357-374, 1991). 델타 수용체는 진통 및 위장관 운동과 여러 가지 호르몬 기능을 매개하는 중추신경계에 풍부하게 존재하며, 뮤 수용체는 아편 의존성 순환기계와 호흡기계 기능 및 여러 가지의 신경 엔도크린 효과를 포함한 모르핀과 관련된 모르핀류 약물과 결합하는 것으로 알려져 있다. 한편 카파 수용체는 수분 발란스, 음식 섭취, 위장관 운동, 체온 조절 및 여러 가지 엔도크린 기능을 포함하여 중추신경계에 폭넓게 분포하고 있다. 이들 세 가지 수용체는 모두 진통효과를 나타낸다 ( Leander et al., J. Pharmacol. Exp. Ther. 234, 463-469, 1985; Morley et al., Peptides 4, 797-800, 1983).The present invention relates to an external preparation composition, and more particularly to an external preparation composition that significantly improved the skin absorption of the hydrophobic drug contained as an active ingredient. Capsaicin (N-vanylyl-trans-8-methyl-6-nonenamide) is a spicy ingredient contained in the juice of capsicum plants and is known to have excellent analgesic activity. It is very effective for analgesic of musculoskeletal system such as arthritis, muscle strain, sprain, tendinitis, bursitis. Kappa receptor agonists that exhibit analgesic and analgesic activity, opiates and derivatives thereof have other pharmacological effects and exhibit potent analgesic and analgesic effects. This is an effect obtained because of its high affinity for the receptor. To date, researchers have reported that there are at least three opiate receptors in the central and peripheral nervous systems. These receptors are known as mu, delta and kappa with unique pharmacological aspects and functions (Wood, PL, Neuropharmacology, 21, 487-497, 1982; Simmon, E., J. Med. Res. Rev., 11, 357 -374, 1991). Delta receptors are abundant in the central nervous system, which mediates pain and gastrointestinal motility and various hormone functions. Mu receptors are morphine-related morphine-related drugs, including opioid-dependent circulatory and respiratory system functions, as well as several neuronal endocrine effects. It is known to bind with. Kappa receptors, on the other hand, are widely distributed in the central nervous system, including water balance, food intake, gastrointestinal motility, thermoregulation, and various endocrine functions. All three receptors have analgesic effects (Leander et al., J. Pharmacol. Exp. Ther. 234, 463-469, 1985; Morley et al., Peptides 4, 797-800, 1983).
이와 같이 캡사이신은 가장 효과적인 치료제로서의 장점을 지니고 있지만, 활성성분은 작열감을 수반한 강한 피부 자극을 나타내어 피부에 불쾌한 자극을 주는 문제점이 있다. 이러한 부작용으로 인하여 캡사이신은 제한된 범위내에서 사용되고 있다. 캡사이신의 피부자극을 줄이기 위한 선행 기술로는 식물 추출액을 이용한 홀트(Holt)의 미합중국 특허 제 5,869,533호와 탈분극과 재분극에 관여하는 상피 신경세포에 작용하여 신경전달 물질을 차단하는 것으로 알려진 수용성 스트론티움 양이온(Sr2+)을 이용한 한(Hahn)의 미합중국 특허 제 5,716,625호가 있다. 일반적으로 이와 같은 제제는 약물의 피부 자극을 차단하는 효과는 있으나, 약물을 투여 후 신속하게 환부에 도달하여 치료효과를 나타내는 데에는 여전히 어려움이 있다.As such, capsaicin has the advantage as the most effective therapeutic agent, but the active ingredient exhibits a strong skin irritation accompanied by a burning sensation, causing an unpleasant stimulus to the skin. Because of these side effects, capsaicin is used to a limited extent. Prior art techniques for reducing skin irritation of capsaicin include Holt, US Pat. No. 5,869,533 using plant extracts and water soluble strontium, which is known to act on epithelial neurons involved in depolarization and repolarization to block neurotransmitters. Hahn US Pat. No. 5,716,625 using cations (Sr2 +). In general, such agents have the effect of blocking the skin irritation of the drug, but it is still difficult to reach the affected area quickly after administration of the drug to exhibit a therapeutic effect.
본 발명자들은 캡사이신의 외용 제제 개발을 위하여 캡사이신이 나타내는 피부자극을 극소화시키기 위하여 용매법에 의해 캡사이신을 포접하였고, 피부에 적용 후 환부에 신속하게 도달하여 치료작용을 나타낼 수 있도록 친수성 비이온성 계면활성제인 폴리옥시에틸렌 알킬에테르류, 폴리에틸렌글리콜 글리세릴 에스테르류, 폴리에틸렌글리콜 글리세릴 에테르류를 배합하여 약물의 피부투과를 촉진하여 우수한 진통 소염 작용을 나타내는 외용 제제를 개발한 것이다.The present inventors encapsulated capsaicin by the solvent method in order to minimize the skin irritation indicated by capsaicin for the development of an external preparation of capsaicin, and it is a hydrophilic nonionic surfactant which can be treated rapidly after application to the skin and exhibit therapeutic action. Polyoxyethylene alkyl ethers, polyethylene glycol glyceryl esters, and polyethylene glycol glyceryl ethers are blended to promote the skin penetration of the drug to develop an external preparation that exhibits excellent analgesic anti-inflammatory action.
본 발명은 캡사이신과 사이클로덱스트린 및 그의 유도체로 이루어진 포접제제와 폴리옥시에틸렌 알킬에테르류, 폴리에틸렌글리콜 글리세릴 에스테르류, 폴리에틸렌글리콜 글리세릴 에테르류를 혼합하여 제조하는 캡사이신 제제 및 그 제조방법을 그 특징으로 한다.The present invention provides a capsaicin preparation prepared by mixing a clathrate consisting of capsaicin, cyclodextrin, and derivatives thereof, polyoxyethylene alkyl ethers, polyethylene glycol glyceryl esters, and polyethylene glycol glyceryl ethers, and a method of manufacturing the same. do.
이와 같은 본 발명을 더욱 상세하게 설명하면 다음과 같다.The present invention will be described in more detail as follows.
본 발명에 따른 캡사이신 제제를 제조하기 위해서는 먼저 캡사이신과 사이클로덱스트린을 메틸렌클로라이드, 클로로포름, 에탄올, 메탄올, 증류수 중에서 선택된 1종 이상의 용매에 용해, 분산하여 포접한 후 회전증발시켜 포접 제제를 제조한다.In order to prepare the capsaicin preparation according to the present invention, capsaicin and cyclodextrin are first dissolved in one or more solvents selected from methylene chloride, chloroform, ethanol, methanol, and distilled water.
본 발명의 조성물에 사용되는 가장 바람직한 사이클로덱스트린과 사이클로덱스트린 유도체는 β-사이클로덱스트린과 그의 유도체로서 히드록시프로필, 히드록시에틸 치환체를 가지는 부분적으로 치환된 β-사이클로덱스트린 에테르 또는 혼합물 에테르이나, 이에 국한되는 것은 아니며, 이들의 사용 중량비는 캡사이신 1 중량부에 대하여 사이클로덱스트린과 사이클로덱스트린 유도체 1∼100 중량부의 범위에서 사용하며, 바람직하게는 1∼50 중량부를 사용하는 것이다. 이는 상기 포접 제제내에서 사이클로덱스트린의 사용 중량비가 캡사이신 1 중량비에 대하여 10 중량부 미만이면 완전한 포접을 형성 할 수 없는 문제가 있으며, 또한 100 중량부를 초과하면 필요량 이상의 사이클로덱스트린을 사용하게 되어 바람직하지 않다.Most preferred cyclodextrins and cyclodextrin derivatives used in the compositions of the present invention are β-cyclodextrins and their partially substituted β-cyclodextrin ethers or mixture ethers having hydroxypropyl, hydroxyethyl substituents, but not limited thereto. The use weight ratio thereof is used in the range of 1 to 100 parts by weight of the cyclodextrin and the cyclodextrin derivative with respect to 1 part by weight of capsaicin, and preferably 1 to 50 parts by weight. This is a problem in that if the use weight ratio of cyclodextrin in the inclusion formulation is less than 10 parts by weight relative to 1 part by weight of capsaicin, it is not possible to form a complete inclusion. .
또한, 본 발명은 상기에서 제조된 포접 제제를 피부에 적용 시 환부에 신속하게 도달하여 치료작용을 나타낼 수 있도록 경피 투여에 적합한 담체로서 친수성 비이온성 계면활성제인 폴리옥시에틸렌 알킬에테르류, 폴리에틸렌글리콜 글리세릴 에스테르류, 폴리에틸렌글리콜 글리세릴 에테르류를 배합하여 캡사이신의 약제학적 조성물을 제조하였다. 상기 담체들은 피부에의 투여를 용이하게 하고 약물을 신속하게 국소 환부에 침투 할 수 있도록 하는 기능을 가지므로서 이들 조성물은 다양한 방법으로, 예를 들면, 경피용 패취, 겔제, 크림제, 용액제, 카타플라스마제, 파스타제로서 투여 될 수 있다.In addition, the present invention is a carrier suitable for transdermal administration so that the inclusion preparations prepared above may reach the affected areas and exhibit therapeutic action when applied to the skin, polyoxyethylene alkyl ethers, polyethylene glycol glycerol, which are hydrophilic nonionic surfactants. Reel esters and polyethylene glycol glyceryl ethers were combined to prepare a pharmaceutical composition of capsaicin. The carriers have the function of facilitating administration to the skin and allowing the drug to quickly infiltrate the local affected area, so that these compositions can be used in various ways, for example, in transdermal patches, gels, creams, solutions. It can be administered as cataplasma, pasta.
폴리옥시에틸렌 알킬에테르류는 Rm(OCH2CH2)nOH 와 같은 일반식으로 표시되며, 여기에서 R은 탄소수 12 내지 20의 알킬기, m은 12 내지 20의 자연수, n은 2 내지 20의 자연수이며, 사용량으로는 캡사이신 1 중량부에 대하여 50∼1000 중량부가 바람직하며, 또한 더욱 바람직한 것은 100∼400 중량부이다.Polyoxyethylene alkyl ethers are represented by a general formula such as Rm (OCH2CH2) nOH, where R is an alkyl group having 12 to 20 carbon atoms, m is a natural number of 12 to 20, n is a natural number of 2 to 20, 50-1000 weight part is preferable with respect to 1 weight part of capsaicin, Furthermore, 100-400 weight part is more preferable.
폴리에틸렌글리콜 글리세릴 에스테르류는 CH3(CH2)7CH=CH(CH2)7CO-(OCH2CH2)nOH 와 같은 일반식으로 표시되며, 여기에서 n은 3 내지 150의 자연수이며, 사용량으로는 캡사이신 1 중량부에 대하여 100∼1000 중량부가 바람직하며, 또한 더욱 바람직한 것은 200∼600 중량부이다.Polyethylene glycol glyceryl esters are represented by the general formula such as CH3 (CH2) 7CH = CH (CH2) 7CO- (OCH2CH2) nOH, where n is a natural number of 3 to 150, and the amount used is 1 part by weight of capsaicin. It is preferably 100 to 1000 parts by weight, and more preferably 200 to 600 parts by weight.
폴리에틸렌글리콜 글리세릴 에테르류는 RCO-OCH2CH(OH)CH2(OCH2CH2)nOH 와 같은 일반식으로 표시되며, 여기에서 RCO는 코코낫 오일에서 유도된 지방산이며, n은 7 내지 80의 자연수이며, 사용량으로는 캡사이신 1 중량부에 대하여 50∼500 중량부가 바람직하며, 또한 더욱 바람직한 것은 100∼200 중량부이다.Polyethylene glycol glyceryl ethers are represented by general formulas such as RCO-OCH2CH (OH) CH2 (OCH2CH2) nOH, where RCO is a fatty acid derived from coconut oil, n is a natural number of 7 to 80 50-500 weight part is preferable with respect to 1 weight part of capsaicin, Furthermore, 100-200 weight part is more preferable.
이러한 폴리옥시에틸렌 알킬에테르류, 폴리에틸렌글리콜 글리세릴 에스테르류, 폴리에틸렌글리콜 글리세릴 에테르류는 분자내에 함유된 알킬기 및 에틸렌옥사이드의 비율에 따라 또는 상호 혼합 비율에 따라서 약물의 피부투과도를 조절할 수 있는 장점을 가지고 있다.Such polyoxyethylene alkyl ethers, polyethylene glycol glyceryl esters, polyethylene glycol glyceryl ethers have the advantage of controlling the skin permeability of the drug according to the ratio of the alkyl group and ethylene oxide contained in the molecule or to the mutual mixing ratio Have.
이하, 본 발명은 다음의 실시예와 실험예에 의해 더욱 상세하게 설명되나, 본 발명이 이들 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail by the following examples and experimental examples, but the present invention is not limited to these examples.
실시예 1Example 1
캡사이신 300㎎Capsaicin 300mg
β-사이클로덱스트린 3g3 g of β-cyclodextrin
에탄올 70㎖Ethanol 70ml
증류수 30㎖30ml of distilled water
캡사이신 300㎎과 β-사이클로덱스트린 3g을 에탄올 70㎖와 증류수 30㎖의 혼합용액에 가하여 용해시키고, 25℃에서 24시간 교반한 다음 회전증발농축기를 사용하여 40℃에서 감압 증류시켜 얻은 고형물을 건조기 상에서 1일 방냉 건조하여 포접화합물을 얻었다.300 mg of capsaicin and 3 g of β-cyclodextrin were dissolved in a mixed solution of 70 ml of ethanol and 30 ml of distilled water, stirred at 25 ° C. for 24 hours, and then distilled under reduced pressure at 40 ° C. using a rotary evaporator on a dryer. It was left to cool for 1 day and dried to obtain an inclusion compound.
실시예 2Example 2
캡사이신 300㎎Capsaicin 300mg
2-하이드록시에틸-β-사이클로덱스트린 3g3 g of 2-hydroxyethyl-β-cyclodextrin
에탄올 70㎖Ethanol 70ml
증류수 30㎖30ml of distilled water
캡사이신 300㎎과 2-하이드록시에틸-β-사이클로덱스트린 3g을 에탄올 70㎖와 증류수 30㎖의 혼합용액에 가하여 용해시키고, 25℃에서 24시간 교반한 다음 회전증발농축기를 사용하여 40℃에서 감압 증류시켜 얻은 고형물을 건조기 상에서 1일 방냉 건조하여 포접화합물을 얻었다.300 mg of capsaicin and 3 g of 2-hydroxyethyl-β-cyclodextrin were added to a mixed solution of 70 ml of ethanol and 30 ml of distilled water, dissolved, and stirred at 25 ° C. for 24 hours, followed by distillation under reduced pressure at 40 ° C. using a rotary evaporator. The solid obtained was cooled and dried on a dryer for 1 day to obtain a clathrate compound.
실시예 3Example 3
캡사이신 300㎎Capsaicin 300mg
2-하이드록시프로필-β-사이클로덱스트린 3g3 g of 2-hydroxypropyl-β-cyclodextrin
에탄올 70㎖Ethanol 70ml
증류수 30㎖30ml of distilled water
캡사이신 300㎎과 2-하이드록시프로필-β-사이클로덱스트린 3g을 에탄올 70㎖와 증류수 30㎖의 혼합용액에 가하여 용해시키고, 25℃에서 24시간 교반한 다음 회전증발농축기를 사용하여 40℃에서 감압 증류시켜 얻은 고형물을 건조기 상에서 1일 방냉 건조하여 포접화합물을 얻었다.300 mg of capsaicin and 3 g of 2-hydroxypropyl-β-cyclodextrin were added to a mixed solution of 70 ml of ethanol and 30 ml of distilled water, dissolved, and stirred at 25 ° C. for 24 hours, followed by distillation under reduced pressure at 40 ° C. using a rotary evaporator. The solid obtained was cooled and dried on a dryer for 1 day to obtain a clathrate compound.
실시예 4Example 4
캡사이신 300㎎Capsaicin 300mg
β-사이클로덱스트린 1.5gβ-cyclodextrin 1.5 g
에탄올 70㎖Ethanol 70ml
증류수 30㎖30ml of distilled water
캡사이신 300㎎과 β-사이클로덱스트린 1.5g을 에탄올 70㎖와 증류수 30㎖의 혼합용액에 가하여 용해시키고, 25℃에서 24시간 교반한 다음 회전증발농축기를 사용하여 40℃에서 감압 증류시켜 얻은 고형물을 건조기 상에서 1일 방냉 건조하여 포접화합물을 얻었다.300 mg of capsaicin and 1.5 g of β-cyclodextrin were added to a mixed solution of 70 ml of ethanol and 30 ml of distilled water, dissolved, stirred at 25 ° C. for 24 hours, and then dried under reduced pressure at 40 ° C. using a rotary evaporator. The mixture was allowed to cool for 1 day on a bed to obtain a clathrate compound.
실시예 5Example 5
캡사이신 300㎎Capsaicin 300mg
β-사이클로덱스트린 7.5g7.5 g of β-cyclodextrin
에탄올 70㎖Ethanol 70ml
증류수 30㎖30ml of distilled water
캡사이신 300㎎과 β-사이클로덱스트린 7.5g을 에탄올 70㎖와 증류수 30㎖의 혼합용액에 가하여 용해시키고, 25℃에서 24시간 교반한 다음 회전증발농축기를 사용하여 40℃에서 감압 증류시켜 얻은 고형물을 건조기 상에서 1일 방냉 건조하여 포접화합물을 얻었다.300 mg of capsaicin and 7.5 g of β-cyclodextrin were added to a mixed solution of 70 ml of ethanol and 30 ml of distilled water, and the mixture was stirred at 25 ° C. for 24 hours and then distilled under reduced pressure at 40 ° C. using a rotary evaporator to dry the solid. The mixture was allowed to cool for 1 day on a bed to obtain a clathrate compound.
실시예 6Example 6
캡사이신(β-사이클로덱스트린 1:10 중량% 포접물) 1Capsaicin (β-cyclodextrin 1:10 wt% Inclusions) 1
폴리옥시에틸렌(2)라우릴에테르 16Polyoxyethylene (2) lauryl ether 16
폴리에틸렌글리콜(7)글리세릴 코코에이트 16Polyethylene glycol (7) glyceryl cocoate 16
폴리에틸렌글리콜(2)올레이트 16Polyethylene glycol (2) oleate 16
폴리옥시에틸렌(2)라우릴에테르, 폴리에틸렌글리콜(7)글리세릴 코코에이트, 폴리에틸렌글리콜(2)올레이트 각 10g을 취하여 약 70℃에서 가열하여 용융시킨 후 캡사이신과 β-사이클로덱스트린 1:10 중량%로 포접한 화합물을 가하여 혼합 용해하여 액상 조성물을 제조하였다.10 g of polyoxyethylene (2) lauryl ether, polyethylene glycol (7) glyceryl cocoate, and polyethylene glycol (2) oleate are taken and melted by heating at about 70 DEG C, and then capsaicin and β-cyclodextrin 1:10 by weight The compound contained in% was added, mixed, and dissolved to prepare a liquid composition.
실시예 7Example 7
캡사이신(2-하이드록시에틸-β-사이클로덱스트린 1:10 중량% 포접물) 1Capsaicin (2-hydroxyethyl-β-cyclodextrin 1:10 wt% inclusions) 1
폴리옥시에틸렌(2)라우릴에테르 16Polyoxyethylene (2) lauryl ether 16
폴리에틸렌글리콜(7)글리세릴 코코에이트 16Polyethylene glycol (7) glyceryl cocoate 16
폴리에틸렌글리콜(2)올레이트 16Polyethylene glycol (2) oleate 16
폴리옥시에틸렌(2)라우릴에테르, 폴리에틸렌글리콜(7)글리세릴 코코에이트, 폴리에틸렌글리콜(2)올레이트 각 10g을 취하여 약 70℃에서 가열하여 용융시킨 후 캡사이신과 2-하이드록시에틸-β-사이클로덱스트린 1:10 중량%로 포접한 화합물을 가하여 혼합 용해하여 액상 조성물을 제조하였다.10 g of polyoxyethylene (2) lauryl ether, polyethylene glycol (7) glyceryl cocoate, and polyethylene glycol (2) oleate are taken and melted by heating at about 70 DEG C, followed by capsaicin and 2-hydroxyethyl-β-. A compound contained in 1: 10% by weight of cyclodextrin was added, mixed and dissolved to prepare a liquid composition.
실시예 8Example 8
캡사이신(2-하이드록시프로필-β-사이클로덱스트린 1:10 중량% 포접물) 1Capsaicin (2-hydroxypropyl-β-cyclodextrin 1:10 wt% inclusions) 1
폴리옥시에틸렌(2)라우릴에테르 16Polyoxyethylene (2) lauryl ether 16
폴리에틸렌글리콜(7)글리세릴 코코에이트 16Polyethylene glycol (7) glyceryl cocoate 16
폴리에틸렌글리콜(2)올레이트 16Polyethylene glycol (2) oleate 16
폴리옥시에틸렌(2)라우릴에테르, 폴리에틸렌글리콜(7)글리세릴 코코에이트, 폴리에틸렌글리콜(2)올레이트 각 10g을 취하여 약 70℃에서 가열하여 용융시킨 후 캡사이신과 2-하이드록시프로필-β-사이클로덱스트린 1:10 중량%로 포접한 화합물을 가하여 혼합 용해하여 액상 조성물을 제조하였다.10 g of polyoxyethylene (2) lauryl ether, polyethylene glycol (7) glyceryl cocoate, and polyethylene glycol (2) oleate are taken and melted by heating at about 70 DEG C, followed by capsaicin and 2-hydroxypropyl-β-. A compound contained in 1: 10% by weight of cyclodextrin was added, mixed and dissolved to prepare a liquid composition.
실험예 1 : 피부자극 시험Experimental Example 1 skin irritation test
실시예 6에서 제조한 외용 조성물과 대조약으로서 조스트릭스(ZOSTRIX ) 크림(Lot No. MBIC-T)을 사용하여, 각 조성물 1g을 건강한 성인 10인의 상완에 도포하여 균질하게 문지른 다음 각 조성물의 피부자극을 평가하였다. 이 평가는 투여 후 24 시간에 걸쳐 다음 4단계로 수행하였으며 그 결과를 표 1에 나타냈다.Using the ZOSTRIX cream (Lot No. MBIC-T) as an external composition prepared in Example 6, 1 g of each composition was applied to the upper arm of 10 healthy adults and rubbed homogeneously, followed by skin of each composition. Stimulation was evaluated. This evaluation was carried out in the following four steps over 24 hours after administration and the results are shown in Table 1.
0 : 피부자극을 못 느낀다.0: Can not feel skin irritation.
1 : 약간 자극을 느낀다.1: feel a little irritating.
2 : 중등도의 자극을 느낀다.2: feel moderate stimulation.
3 : 고도의 자극을 느낀다.3: feel a high stimulus.
[표1]Table 1
실험예 2 : 웅성 무모 마우스(Hairless mouse)의 피부를 이용한 약물 투과 시험Experimental Example 2: Drug penetration test using skin of male hairless mouse
체중 15∼20g의 웅성 무모마우스를 경추 탈골법으로 희생시키고 적출된 피부의 피하지방과 조직물을 제거하여 투과 시험에 사용하였다. 피부 투과 시험을 위한 확산셀(Franz Diffusion Cell)에 적출 피부를 장착하여, 실시예 6∼8에서 제조한 외용 조성물과 대조군으로서 조스트릭스(ZOSTRIX ) 크림(Lot No. MBIC-T)의 각 조성물 1g을 피부표면에 도포한 후 일정시간 간격으로 검체를 채취하여 전처리 후 고속액체크로마토그래피법으로 투과된 약물량을 분석하여 그 결과를 표 2에 나타냈다.Male hairless mice with a body weight of 15-20 g were sacrificed by cervical dislocation and subcutaneous fat and tissues of the extracted skin were removed and used in the permeation test. 1 g of each composition of ZOSTRIX cream (Lot No. MBIC-T) as a control composition and the external composition prepared in Examples 6 to 8 were mounted on a dermal diffusion cell for the skin permeation test. After the coating was applied to the skin surface, samples were taken at regular intervals, and after the pretreatment, the amount of drug permeated by high-performance liquid chromatography was analyzed and the results are shown in Table 2.
[표2][Table 2]
상술한 바와 같이, 본 발명은 캡사이신을 유효성분으로 하고 캡사이신을 사이클로덱스트린으로 포접하여 현저하게 피부 자극을 감소 시켰으며, 피부에 적용 후 환부에 신속하게 도달하여 치료작용을 나타낼 수 있도록 친수성 비이온성 계면활성제인 폴리옥시에틸렌 알킬에테르류, 폴리에틸렌글리콜 글리세릴 에스테르류, 폴리에틸렌글리콜 글리세릴 에테르류를 배합하여 약물의 피부투과를 촉진하는 작용을 나타내는 외용 제제임을 알 수 있다.As described above, the present invention has a significant reduction in skin irritation by capsaicin as an active ingredient and capsaicin by cyclodextrin, and a hydrophilic nonionic interface that can rapidly reach the affected area after application to the skin and exhibit therapeutic action. It can be seen that it is an external preparation that exhibits an action of promoting skin permeation of the drug by combining polyoxyethylene alkyl ethers, polyethylene glycol glyceryl esters, and polyethylene glycol glyceryl ethers which are active agents.
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| US7081590B2 (en) | 2002-02-27 | 2006-07-25 | Seiko Epson Corporation | Wiring board and method of fabricating tape-like wiring substrate |
| KR101478520B1 (en) * | 2014-01-24 | 2015-01-02 | 동신대학교산학협력단 | Capsaicin-Peptide Having Improved Safety for Skin and Cosmetic External Preparation Composition for Skin Using the Same |
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| KR101866010B1 (en) * | 2016-02-17 | 2018-06-08 | 경남대학교 산학협력단 | A Method for Manufacturing Microcapsules of the Capsaicin in a Hot Pepper |
| KR102107894B1 (en) * | 2018-02-14 | 2020-05-26 | 경남대학교 산학협력단 | A method for manufacturing microcapsules of the capsaicin in powered red pepper and red pepper seed |
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| US5856361A (en) * | 1996-04-23 | 1999-01-05 | Medical Merchandising, Inc. | Pain reliever and method of use |
| US5885597A (en) * | 1997-10-01 | 1999-03-23 | Medical Research Industries,Inc. | Topical composition for the relief of pain |
| JPH11199518A (en) * | 1997-12-26 | 1999-07-27 | Lion Corp | Warm sense-giving composition and preparation for external use for skin |
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| KR101478520B1 (en) * | 2014-01-24 | 2015-01-02 | 동신대학교산학협력단 | Capsaicin-Peptide Having Improved Safety for Skin and Cosmetic External Preparation Composition for Skin Using the Same |
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