KR101846773B1 - Self assembled nanoparticle containing retinol efficiently and preparing method thereof - Google Patents
Self assembled nanoparticle containing retinol efficiently and preparing method thereof Download PDFInfo
- Publication number
- KR101846773B1 KR101846773B1 KR1020170014360A KR20170014360A KR101846773B1 KR 101846773 B1 KR101846773 B1 KR 101846773B1 KR 1020170014360 A KR1020170014360 A KR 1020170014360A KR 20170014360 A KR20170014360 A KR 20170014360A KR 101846773 B1 KR101846773 B1 KR 101846773B1
- Authority
- KR
- South Korea
- Prior art keywords
- self
- retinol
- phea
- polyamino acid
- acid derivative
- Prior art date
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- 239000002105 nanoparticle Substances 0.000 title claims abstract description 62
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 title claims abstract description 60
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Classifications
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
- C08G73/10—Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors
- C08G73/1092—Polysuccinimides
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- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
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Abstract
Description
본 발명은 주름개선 기능성 원료로 사용되는 레티놀이 효과적으로 함유된 주름개선 자기조립 나노입자 및 이의 제조 방법에 관한 것이다.The present invention relates to a wrinkle-improving self-assembled nanoparticle effectively containing retinol used as a wrinkle-reducing functional raw material and a method for producing the same.
레티놀은 비타민 A의 한 종류로, 순수비타민이라고도 하며, 활성 형태인 레티노익산(retinoic acid)으로 변형되기도 하며, 표피세포가 원래의 기능을 유지하는 데 중요한 역할을 하는 것으로 알려져 있다. 이러한 이유로 레티놀은 화장품 산업에서 고기능성 제품 중 주름개선 기능성의 주원료로 사용되고 있다.Retinol is a type of vitamin A, also known as pure vitamin, and is also known as retinoic acid, an active form, and plays an important role in maintaining the original function of the epidermal cells. For this reason, retinol has been used as a main ingredient in wrinkle-improving functionalities in high-performance products in the cosmetics industry.
다만, 레티놀은 산화에 민감하고 빛과 열에 불안정한 구조를 나타내기 때문에 이러한 불안정성과 피부자극 문제를 개선하기 위해 레티놀 유도체가 개발되어 주름개선 화장품의 원료로 사용되고 있다.However, since retinol is sensitive to oxidation and unstable to light and heat, retinol derivatives have been developed to improve such instability and skin irritation and are used as raw materials for cosmetic wrinkles.
상기 문제점을 해결하기 위해 레티놀을 안정하게 포집하고 그 효과가 증대되는 원료에 대해 연구 개발되고 있으나, 아직 그 성과는 미미하다.In order to solve the above-mentioned problems, researches have been conducted on raw materials that stably capture retinol and increase its effect, but the results are still small.
따라서, 기능성 및 약용 화장품 산업에 기여할 수 있도록 기능성 화장품 주원료로 주목 받고 있는 레티놀을 안정적으로 포집 및 피부에 전달할 수 있는 나노제재에 대한 연구 개발이 시급한 실정이다. Therefore, it is urgent to research and develop nano-materials capable of stably capturing and transferring retinol, which is attracting attention as a main ingredient of functional cosmetics, to contribute to the functional and medicinal cosmetic industry.
본 발명의 목적은 수용액상에서 자기조립 나노입자를 형성할 수 있는 레티노익산이 접목된 양친성 폴리아미노산 유도체를 합성하여 이를 자기조립에 의해 레티놀을 안정적으로 포집 및 전달할 수 있는 레티놀이 효과적으로 함유된 주름개선 자기조립 나노입자 및 이의 제조 방법을 제공하는 데에 있다.It is an object of the present invention to provide an amphipathic polyamino acid derivative grafted with retinoic acid capable of forming self-assembled nanoparticles in an aqueous solution, which is capable of stably collecting and delivering retinol by self-assembly, Self-assembled nanoparticles and a method of manufacturing the same.
상기 목적을 달성하기 위하여, 본 발명은 하기 화학식 1로 표시되는 양친성 폴리아미노산 유도체를 제공한다.In order to achieve the above object, the present invention provides an amphiphilic polyamino acid derivative represented by the following general formula (1).
[화학식 1][Chemical Formula 1]
상기 화학식 1에서, R1 내지 R2는 서로 상이하고,In Formula 1, R 1 to R 2 are different from each other,
수소 또는 하기 화학식 1-1로 표시되는 화합물이며,Hydrogen or a compound represented by the following formula (1-1)
[화학식 1-1][Formula 1-1]
상기 n은 2 내지 600의 정수임.And n is an integer of 2 to 600.
또한 본 발명은 상기 양친성 폴리아미노산 유도체를 하나 이상 포함하며 자기조립되는, 자기조립 나노입자를 제공한다.The present invention also provides self-assembled nanoparticles comprising at least one amphipathic polyamino acid derivative and being self-assembled.
또한 본 발명은 상기 자기조립 나노입자 및 상기 자기조립 나노입자 내에 봉입되는 레티놀을 포함하는, 주름개선용 조성물을 제공한다.The present invention also provides a wrinkle-improving composition comprising the self-assembled nanoparticles and the retinol enclosed in the self-assembled nanoparticles.
또한 본 발명은 폴리숙신이미드(polysuccinimide; 이하 'PSI')를 에탄올아민(ethanolamine)과 반응시켜 폴리(2-히드록시에틸 아스파르타마이드)(poly(2-hydroxyethyl aspartamide); 이하 'PHEA')를 준비하는 단계; 상기 PHEA에 레티노이드 유도체를 접목시켜 양친성 폴리아미노산 유도체를 합성하는 단계; 상기 합성된 양친성 폴리아미노산 유도체를 수용액에 첨가하여 자기조립 나노입자를 준비하는 단계; 상기 자기조립 나노입자가 형성된 수용액에 레티놀을 첨가하고 혼합한 후 초음파 처리하여 레티놀이 봉입된 주름개선용 조성물을 합성하는 단계;를 포함하는, 주름개선용 조성물 제조방법을 제공한다.The present invention also relates to a process for preparing poly (2-hydroxyethyl aspartamide) (PHEA) by reacting polysuccinimide (PSI) with ethanolamine, ; Synthesizing an amphiphilic polyamino acid derivative by grafting a retinoid derivative to the PHEA; Preparing a self-assembled nanoparticle by adding the synthesized amphiphilic polyamino acid derivative to an aqueous solution; The present invention also provides a method for producing a composition for improving wrinkles, which comprises adding retinol to an aqueous solution having the self-assembled nanoparticles formed therein, mixing and then ultrasonically treating the wrinkle-improving composition.
본 발명에 따른 레티놀이 효과적으로 함유된 주름개선 자기조립 나노입자 및 이의 제조 방법은 친수성 고분자 백본에 레티노익산을 접목시킴으로써 양친성 폴리아미노산 유도체를 합성할 수 있고, 소수성 고분자인 레티노익산에 의해 수용액상에서 자기조립 나노입자를 형성할 수 있다. 레티놀을 가장 안정적으로 포집하는 레티노익산의 최적의 접목도를 적용함으로써 레티놀과 구조적으로 유사하여 레티놀을 안정적으로 포집 및 전달할 수 있는 주름개선제 전달체로 응용할 수 있다.The self-assembled wrinkle-modified nanoparticles and the method for producing the same according to the present invention can effectively produce an amphiphilic polyamino acid derivative by grafting retinoic acid to the hydrophilic polymer backbone, and can produce self-assembled nanoparticles of retinoic acid by retinoic acid, which is a hydrophobic polymer, It is possible to form assembled nanoparticles. By applying the optimum degree of grafting of retinoic acid that captures retinol most stably, it can be applied as a wrinkle-improving agent delivery agent capable of stably capturing and delivering retinol, structurally similar to retinol.
도 1은 레티노익산이 접목된 양친성 폴리아미노산 유도체 합성 과정을 나타낸 도면;
도 2는 레티노익산이 접목된 양친성 폴리아미노산 유도체의 1H-NMR 분석을 나타낸 도면;
도 3은 실험예 3에 따른 레티노익산이 접목된 양친성 폴리아미노산 유도체의 자기조립 현상을 확인하기 위해 CAC 측정 결과를 나타낸 도면;
도 4는 자기조립 나노입자 형태를 나타낸 도면(R5-PHEA(a), R10-PHEA(b), 및 R19-PHEA(c)); 및
도 5는 레티놀 포집 최적 접목도를 갖는 주름개선제 전달체(R5-PHEA(a), R10-PHEA(b), 및 R19-PHEA(c))를 나타낸 도면이다.1 shows a process for synthesizing an amphipathic polyamino acid derivative having retinoic acid conjugated thereto;
2 shows 1 H-NMR analysis of an amphipathic polyamino acid derivative grafted with retinoic acid;
FIG. 3 is a graph showing the results of CAC measurement to confirm the self-assembly phenomenon of an amphipathic polyamino acid derivative grafted with retinoic acid according to Experimental Example 3; FIG.
FIG. 4 is a drawing (R5-PHEA (a), R10-PHEA (b), and R19-PHEA (c)) showing the morphology of self-assembled nanoparticles; And
5 is a view showing a wrinkle-improving agent carrier (R5-PHEA (a), R10-PHEA (b), and R19-PHEA (c)) having an optimum degree of grafting with retinol.
이하, 본 발명인 레티놀이 효과적으로 함유된 주름개선 자기조립 나노입자 및 이의 제조 방법을 보다 상세하게 설명한다.Hereinafter, the self-assembled wrinkle-modified nano-particles effectively containing retinol and a method for producing the same will be described in detail.
본 발명의 발명자들은 레티놀은 화장품 산업에서 주름개선 기능성 화장품의 주원료로 이용되고 있으나 산화에 민감하고 빛과 열에 불안정한 구조를 갖고 있어 레티놀을 안정하게 피부에 전달할 수 있는 기술에 대해 연구 개발 하던 중, 레티노익산은 양친성 폴리머의 소수성 분자단으로 작용하여 수용액상서 자기조립 나노입자를 형성할 뿐 아니라 레티놀과 구조적으로 유사하여 레티놀을 안정적으로 포집 및 전달할 수 있음을 밝혀내어 본 발명을 완성하였다.The inventors of the present invention have found that while retinol is used as a main ingredient of wrinkle-improving functional cosmetics in the cosmetics industry, it has a structure that is sensitive to oxidation and unstable to light and heat and thus can transfer retinol to the skin stably. Iksan acts as a hydrophobic molecular end of the amphipathic polymer to form self-assembled nanoparticles on an aqueous solution, and is structurally similar to retinol to stably trap and transfer retinol, thereby completing the present invention.
본 발명은 하기 화학식 1로 표시되는 양친성 폴리아미노산 유도체를 제공한다.The present invention provides amphiphilic polyamino acid derivatives represented by the following general formula (1).
[화학식 1][Chemical Formula 1]
상기 화학식 1에서, R1 내지 R2는 서로 상이하고,In Formula 1, R 1 to R 2 are different from each other,
수소 또는 하기 화학식 1-1로 표시되는 화합물이며,Hydrogen or a compound represented by the following formula (1-1)
[화학식 1-1][Formula 1-1]
상기 n은 2 내지 600의 정수임.And n is an integer of 2 to 600.
폴리아미노산은 완전한 수용성 고분자로 생체 적합성이 우수하고 독성이 없어 고분자를 이용한 약물의 전구체를 설계하는데 응용이 가능하다. 또한 말단의 하이드록시기와 다른 물질의 접합이 용이하여 다양한 형태의 전달체를 설계하는데 있어서 전구체로 상당히 용이한 물질이다.Polyamino acid is a completely water-soluble polymer. It has excellent biocompatibility and is not toxic, so it can be applied to the design of drug precursor using polymer. In addition, it is a substance which is easy to precisely as a precursor in designing various types of transporters by facilitating bonding of terminal hydroxyl groups with other materials.
상기 양친성 폴리아미노산 유도체는 폴리숙신이미드(polysuccinimide; 이하 'PSI')를 원료로 하여 얻어진 폴리(2-히드록시에틸 아스파르타마이드)(poly(2-hydroxyethyl aspartamide); 이하 'PHEA')에 화학식 1-1로 표시되는 화합물을 접목시킨 것일 수 있으며, 이에 제한되는 것은 아니다.The amphiphilic polyamino acid derivative is obtained by reacting poly (2-hydroxyethyl aspartamide) (hereinafter referred to as "PHEA") obtained by using polysuccinimide (PSI) May be grafted with a compound represented by the general formula (1-1), but is not limited thereto.
상기 양친성 폴리아미노산 유도체는 PSI에 접목된 화학식 1-1로 표시되는 화합물의 접목도가 5 내지 30 mol%일 수 있으며, 이에 제한되는 것은 아니다.The amphiphilic polyamino acid derivative may have a degree of grafting of 5 to 30 mol% of the compound represented by formula (1-1) grafted to PSI, but is not limited thereto.
또한 본 발명은 상기 양친성 폴리아미노산 유도체를 하나 이상 포함하며 자기조립되는, 자기조립 나노입자를 제공한다.The present invention also provides self-assembled nanoparticles comprising at least one amphipathic polyamino acid derivative and being self-assembled.
또한 본 발명은 상기 자기조립 나노입자 및 상기 자기조립 나노입자 내에 봉입되는 레티놀을 포함하는, 주름개선용 조성물을 제공한다.The present invention also provides a wrinkle-improving composition comprising the self-assembled nanoparticles and the retinol enclosed in the self-assembled nanoparticles.
상기 조성물은 화장료 조성물, 약학 조성물 또는 건강기능식품일 수 있으며, 이에 제한되는 것은 아니다.The composition may be a cosmetic composition, a pharmaceutical composition or a health functional food, but is not limited thereto.
상기 화장료 조성물은 유효성분인 본 발명에 따른 화합물 외에 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함할 수 있다.The cosmetic composition may contain, in addition to the compound according to the present invention as an active ingredient, conventional additives such as stabilizers, solubilizers, vitamins, pigments and fragrances, and carriers.
상기 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 한정되는 것은 아니다. 보다 상세하게는, 썬 크림, 유연 화장수, 수렴 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.The cosmetic composition may be prepared in any form conventionally produced in the art and may be in the form of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, oil, powder foundation, emulsion foundation, Wax foundation, spray, and the like. However, the present invention is not limited thereto. More specifically, it can be manufactured in the form of a sun cream, a flexible lotion, a convergent lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a pack, a spray or a powder.
상기 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation is a paste, cream or gel, an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component .
상기 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, chlorofluorohydrocarbons, propane / Or propellants such as dimethyl ether.
상기 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해 화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation is a solution or an emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, - butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid esters of sorbitan.
상기 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, a microcrystalline cellulose , Aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
상기 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical compositions may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to conventional methods.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물은 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제할 수 있다.In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose sucrose), lactose, gelatin, and the like.
또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.
상기 약학조성물의 유효성분인 화합물의 사용량은 환자의 나이, 성별, 체중, 질환에 따라 달라질 수 있으나, 0.001 내지 100mg/kg으로, 바람직하게는 0.01 내지 10 mg/kg을 일일 1회 내지 수회 투여할 수 있다. The amount of the compound which is an active ingredient of the pharmaceutical composition may vary depending on the age, sex, weight and disease of the patient, but it is preferably 0.001 to 100 mg / kg, preferably 0.01 to 10 mg / kg, .
상기 약학 조성물의 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The dosage of the pharmaceutical composition may be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
상기 약학 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 기관지내 흡입, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다.The pharmaceutical composition may be administered to mammals such as rats, mice, livestock, humans, and the like in a variety of routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intratracheal, intrauterine or intracerebroventricular injections.
또한, 상기 건강기능식품은 분말, 과립, 정제, 캡슐, 시럽 또는 음료의 형태로 제공될 수 있으며, 상기 건강기능식품은 유효성분인 본 발명에 따른 화합물 이외에 다른 식품 또는 식품 첨가물과 함께 사용되고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 그의 사용 목적 예를들어 예방, 건강 또는 치료적 처치에 따라 적합하게 결정될 수 있다.The health functional food may be provided in the form of a powder, a granule, a tablet, a capsule, a syrup or a drink. The health functional food may be used together with food or food additives other than the compound according to the present invention, Can be suitably used according to the method of The amount of the active ingredient to be mixed can be suitably determined according to its use purpose, for example, prevention, health or therapeutic treatment.
상기 건강기능식품에 함유된 화합물의 유효용량은 상기 약학조성물의 유효용량에 준해서 사용할 수 있으나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있으며, 유효성분은 안전성 면에서 아무런 문제가 없기 때문에 상기 범위 이상의 양으로도 사용될 수 있음은 확실하다.The effective dose of the compound contained in the health functional food may be used in accordance with the effective dose of the pharmaceutical composition, but may be less than the above range for the purpose of health and hygiene or long-term intake for health control purposes , It is clear that the active ingredient can be used in an amount exceeding the above range since there is no problem in terms of safety.
상기 건강기능식품의 종류에는 특별한 제한이 없고, 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등을 들 수 있다.There is no particular limitation on the kind of the above health functional food and examples thereof include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, , Drinks, alcoholic beverages and vitamin complexes.
또한 본 발명은 폴리숙신이미드(polysuccinimide; 이하 'PSI')를 에탄올아민(ethanolamine)과 반응시켜 폴리(2-히드록시에틸 아스파르타마이드)(poly(2-hydroxyethyl aspartamide); 이하 'PHEA')를 준비하는 단계; 상기 PHEA에 레티노이드 유도체를 접목시켜 양친성 폴리아미노산 유도체를 합성하는 단계; 상기 합성된 양친성 폴리아미노산 유도체를 수용액에 첨가하여 자기조립 나노입자를 준비하는 단계; 상기 자기조립 나노입자가 형성된 수용액에 레티놀을 첨가하고 혼합한 후 초음파 처리하여 레티놀이 봉입된 주름개선용 조성물을 합성하는 단계;를 포함하는, 주름개선용 조성물 제조방법을 제공한다.The present invention also relates to a process for preparing poly (2-hydroxyethyl aspartamide) (PHEA) by reacting polysuccinimide (PSI) with ethanolamine, ; Synthesizing an amphiphilic polyamino acid derivative by grafting a retinoid derivative to the PHEA; Preparing a self-assembled nanoparticle by adding the synthesized amphiphilic polyamino acid derivative to an aqueous solution; The present invention also provides a method for producing a composition for improving wrinkles, which comprises adding retinol to an aqueous solution having the self-assembled nanoparticles formed therein, mixing and then ultrasonically treating the wrinkle-improving composition.
상기 레티노이드 유도체는 레티닐아세티에트, 레티닐팔미테이트, 레티놀, 및 레티노익산으로 이루어진 군에서 선택된 어느 하나일 수 있으며, 이에 제한되는 것은 아니다.The retinoid derivative may be any one selected from the group consisting of retinoic acidet, retinyl palmitate, retinol, and retinoic acid, but is not limited thereto.
상기 양친성 폴리아미노산 유도체는 PSI에 접목된 화학식 1-1로 표시되는 화합물의 접목도가 5 내지 30 mol%인 것일 수 있으며, 이에 제한되는 것은 아니다.The amphiphilic polyamino acid derivative may have an degree of grafting of 5 to 30 mol% of the compound represented by the general formula (1-1) grafted to PSI, but is not limited thereto.
구체적으로, 레티노이드 유도체를 PHEA 백본 단위(unit) 당 5%, 10%, 및 30%(feed mol%)를 첨가하여 접목도를 제어할 수 있고, 접목된 치환 정도(Degree of substitution; 이하 'DS')는 전체 PSI 단위 마다 접목(grafting)된 레티노익산의 몰 퍼센트를 의미한다. Specifically, the degree of grafting can be controlled by adding 5%, 10%, and 30% (feed mol%) of retinoid derivatives per unit of PHEA backbone, and the degree of substitution 'Refers to the molar percentage of retinoic acid grafted per entire PSI unit.
접목 코폴리머(graft copolymer)의 DS는 1H-NMR를 측정하여 하기 수학식 (1)에 따라 계산할 수 있다. The DS of the graft copolymer can be calculated according to the following formula (1) by measuring 1 H-NMR.
[수학식 1][Equation 1]
1H-NMR 분석과 계산을 통해 얻은 접목도는 0.1 mol%에서 70 mol%까지 다양하게 레티노익산을 폴리아미노산 백본에 접목시킬 수 있다. The degree of grafting obtained from 1 H-NMR analysis and calculation can be varied from 0.1 mol% to 70 mol%, and the retinoic acid can be grafted onto the polyamino acid backbone.
소수성 고분자의 접목도(DS)가 작을 때는 증류수 분산이 용이하지만, 접목도가 클 때에는 증류수에 분산이 어려운 문제점이 있다. 따라서 친수성 폴리머 백본과 소수성 분자를 모두 녹일 수 있는 상기 용매로서, 디메틸설폭사이드(dimetyl sulfoxide, DMSO)), 디메틸포름아마이드(dimetyl formamide), DMF), 및 테트라히드로퓨란(tetrahydrofuran, THF)으로 이루어진 군에서 선택된 어느 하나를 이용하는 것이 보다 바람직하다.When the degree of grafting (DS) of the hydrophobic polymer is small, distilled water can be easily dispersed, but when the degree of grafting is large, it is difficult to disperse in distilled water. Thus, the solvent which can dissolve both the hydrophilic polymer backbone and the hydrophobic molecule is a group consisting of dimethyl sulfoxide (DMSO), dimethyl formamide, DMF, and tetrahydrofuran (THF) It is more preferable to use any one selected from the above.
상기 자기조립 나노입자는 평균 직경이 50 내지 90 nm인 것일 수 있으며, 이에 제한되는 것은 아니다.The self-assembled nanoparticles may have an average diameter of 50 to 90 nm, but are not limited thereto.
상기 주름개선용 조성물을 합성하는 단계는 자기조립 나노입자가 형성된 수용액에 레티놀을 첨가하고 2000 내지 4000 rpm으로 5 내지 10분 동안 혼합한 후 5 내지 15분 동안 초음파 처리할 수 있으며, 이에 제한되는 것은 아니다.The step of synthesizing the composition for improving wrinkles may be performed by adding retinol to an aqueous solution in which the self-assembled nanoparticles are formed, mixing the mixture at 2000 to 4000 rpm for 5 to 10 minutes, and then sonicating for 5 to 15 minutes, no.
이하, 하기 실시예에 의해 본 발명인 레티놀이 효과적으로 함유된 주름개선 자기조립 나노입자 및 이의 제조 방법을 보다 상세하게 설명한다. 다만, 이러한 실시예에 의해 본 발명이 한정되는 것은 아니다.Hereinafter, the self-assembled wrinkle-modified nanoparticles effectively containing retinol of the present invention and a method for producing the same will be described in more detail with reference to the following examples. However, the present invention is not limited by these examples.
<실시예 1> 양친성 폴리아미노산 유도체 및 이를 이용한 레티놀이 봉입된 주름개선용 조성물 합성Example 1 Synthesis of an Amphipathic Polyamino Acid Derivative and a Wrinkle-Reducing Composition Containing Retinol Using It
1. 폴리(2-히드록시에틸 아스파르타마이드)(poly(2-hydroxyethyl aspartamide); 이하 'PHEA')합성1. Synthesis of poly (2-hydroxyethyl aspartamide) (hereinafter referred to as 'PHEA')
25℃, 디메틸포름아마이드(dimethyl formamide; 이하 'DMF') 조건 하에서, 전구체로 합성한 폴리숙신이미드(polysuccinimide; 이하 'PSI')를 에탄올아민(ethanolamine)과 반응시켜 친수성 폴리머 백본인 PHEA를 합성하였다.PHU (hydrophilic polymer backbone) was synthesized by reacting polysuccinimide (PSI) synthesized as a precursor with ethanolamine under dimethyl formamide (DMF) at 25 ° C. Respectively.
2. 레티노익산이 접목된 PHEA 합성2. Synthesis of PHEA grafted with retinoic acid
상기 합성된 PHEA와 소수성 고분자인 레티노익산(5 mol%)을 DMF에 용해시킨 후, N,N'-Dicyclohexylcarboiimide(DCC)와 4-dimethylaminopyridine(DMAP)를 첨가한 후 교반하여 양친성 폴리아미노산 유도체인 레티노익산이 접목(grafting)된 PHEA를 합성하였고, 이를 'R5-PHEA'로 명명하였다.The synthesized PHEA and the hydrophobic polymer, retinoic acid (5 mol%), were dissolved in DMF. N, N'-Dicyclohexylcarboiimide (DCC) and 4-dimethylaminopyridine (DMAP) were added and stirred to obtain an amphiphilic polyamino acid derivative PHEA, grafted with retinoic acid, was synthesized and named 'R5-PHEA'.
3. 레티놀이 봉입된 주름개선용 조성물 합성3. Synthetic composition for wrinkle filling with retinol
상기 합성된 R5-PHEA 3 mg을 7.5 ㎖ 수용액에 넣어 투석 및 침전(dialysis and precipitation) 방법으로 평균 직경이 89 nm인 자기조립 나노입자를 형성시킨 후, 0.15 μg/㎖ 농도로 클로로포름에 용해되어 있는 레티놀 10 μL을 첨가하고 3000 rpm으로 5분간 vortex 혼합한 후, 즉시 10분간 초음파 처리하여 레티놀을 자기조립 나노입자에 봉입해 주었다.3 mg of the synthesized R5-PHEA was added to 7.5 ml of an aqueous solution to form self-assembled nanoparticles having an average diameter of 89 nm by dialysis and precipitation, and then dissolved in chloroform at a concentration of 0.15 μg / ml 10 μL of retinol was added and vortexed at 3000 rpm for 5 minutes. Immediately, the mixture was sonicated for 10 minutes to contain retinol in self-assembled nanoparticles.
<실시예 2> 양친성 폴리아미노산 유도체 및 이를 이용한 레티놀이 봉입된 주름개선용 조성물 합성Example 2 Amphiphilic Polyamino Acid Derivatives and Synthetic Composition for Wrinkle Containing Encapsulated Retinol Using the same
소수성 고분자인 레티노익산(10 mol%)을 이용하여 레티노익산이 접목된 PHEA를 합성(이하 'R10-PHEA')하여 평균 직경이 74 nm인 자기조립 나노입자를 합성한 것을 제외하고는, 상기 실시예 1과 동일한 조건으로 레티놀이 봉입된 주름개선용 조성물을 합성하였다.Except that a self-assembled nanoparticle having an average diameter of 74 nm was synthesized by synthesizing PHEA grafted with retinoic acid using retinoic acid (10 mol%) as a hydrophobic polymer (hereinafter referred to as 'R10-PHEA'). A composition for improving wrinkles in which retinol was enclosed under the same conditions as in Example 1 was synthesized.
<실시예 3> 양친성 폴리아미노산 유도체 및 이를 이용한 레티놀이 봉입된 주름개선용 조성물 합성Example 3 Synthesis of Amphipathic Polyamino Acid Derivatives and Wrinkle-Reducing Compositions Containing Retinol Using the Derivatives
소수성 고분자인 레티노익산(19 mol%)을 이용하여 레티노익산이 접목된 PHEA를 합성(이하 'R19-PHEA')하여 평균 직경이 68 nm인 자기조립 나노입자를 합성한 것을 제외하고는, 상기 실시예 1과 동일한 조건으로 레티놀이 봉입된 주름개선용 조성물을 합성하였다.Except that a self-assembled nanoparticle having an average diameter of 68 nm was synthesized by synthesizing PHEA grafted with retinoic acid (hereinafter referred to as 'R19-PHEA') using retinoic acid (19 mol%) as a hydrophobic polymer. A composition for improving wrinkles in which retinol was enclosed under the same conditions as in Example 1 was synthesized.
<실시예 4> 양친성 폴리아미노산 유도체 및 이를 이용한 레티놀이 봉입된 주름개선용 조성물 합성Example 4 Amphiphilic Polyamino Acid Derivatives and Synthesized Compositions for Retaining Wrinkles Containing Retinol
소수성 고분자인 레티노익산(30 mol%)을 이용하여 레티노익산이 접목된 PHEA를 합성(이하 'R30-PHEA')하여 평균 직경이 51 nm인 자기조립 나노입자를 합성한 것을 제외하고는, 상기 실시예 1과 동일한 조건으로 레티놀이 봉입된 주름개선용 조성물을 합성하였다.Except that a self-assembled nanoparticle having an average diameter of 51 nm was synthesized by synthesizing PHEA grafted with retinoic acid using hydrophobic polymer retinoic acid (30 mol%) (hereinafter referred to as 'R30-PHEA'). A composition for improving wrinkles in which retinol was enclosed under the same conditions as in Example 1 was synthesized.
<실험예 1> <Experimental Example 1> 1One H-NMR 분석H-NMR analysis
1. PHEA의 1. PHEA 1One H-NMR 분석H-NMR analysis
1H-NMR결과 2.7-2.9 ppm, 3.3 ppm, 3.7 ppm에서 PHEA의 methylene proton과 4.7 ppm에서 methine proton을 확인함으로써 PHEA의 성공적인 합성을 알 수 있다. 1 H-NMR results confirm the successful synthesis of PHEA by confirming the methylene proton of PHEA and the methine proton at 4.7 ppm at 2.7-2.9 ppm, 3.3 ppm and 3.7 ppm.
2. 레티노익산이 접목된 PHEA(이하 'R-PHEA') 분석2. Analysis of PHEA (hereinafter referred to as 'R-PHEA') grafted with retinoic acid
1H-NMR결과 레티노익산의 벤젠링과 PHEA 백본의 특성 chemical shifts를 확인함으로써 R-PHEA의 성공적인 합성을 알 수 있다. 또한, 3.1-3.2 ppm 의 PHEA methylene proton 과 1.1-1.2 ppm의 레티노익산 benzene proton 픽의 integration을 비교하여 레티노익산의 접목도(DS)를 구할 수 있다. 1 H-NMR shows the successful synthesis of R-PHEA by confirming the chemical shifts of the benzene ring of retinoic acid and the PHEA backbone. In addition, the degree of grafting (DS) of retinoic acid can be obtained by comparing the integration of 3.1-3.2 ppm PHEA methylene proton with 1.1-1.2 ppm retinoic acid benzene proton pick.
<실험예 2> 자기조립 나노입자의 크기분포 분석<Experimental Example 2> Analysis of size distribution of self-assembled nanoparticles
동적 광산란(Dynamic light scattering; 이하 'DLS') 측정법으로 수력학적 직경을 측정하였다.The hydrodynamic diameter was measured by dynamic light scattering (DLS) measurement.
구체적으로, DLS 측정은 He-Ne 레이저를 사용하여 90°산란각에서, Malvern Inc. 기기를 이용하여 측정하였고, 모든 데이터들은 5 회 측정의 평균값이다.Specifically, the DLS measurement was performed using a He-Ne laser at a 90 ° scatter angle, All data were averages of 5 measurements.
실시예 1에 따라 제조된 R5-PHEA을 수용액에 넣어 형성된 자기조립 나노입자의 평균 직경이 89 nm이고, 실시예 2에 따라 제조된 R10-PHEA을 수용액에 넣어 형성된 자기조립 나노입자의 평균 직경이 74 nm이며, 또한 실시예 4에 따라 제조된 R30-PHEA을 수용액에 넣어 형성된 자기조립 나노입자의 평균 직경이 51 nm로 측정되었다. The average diameter of the self-assembled nanoparticles formed by putting the R5-PHEA prepared in Example 1 into the aqueous solution was 89 nm, and the average diameter of the self-assembled nanoparticles formed by putting the R10-PHEA prepared in Example 2 into the aqueous solution was 74 nm, and the average diameter of the self-assembled nanoparticles formed by adding R30-PHEA prepared in Example 4 into an aqueous solution was measured to be 51 nm.
이는 친수성 폴리머 백본인 PHEA에 소수성 고분자인 레티노익산이 접목되는 접목도가 증가할수록, 즉 레티노익산의 mol%가 증가할수록 양친성 폴리아미노산 유도체로부터 형성되는 자기조립 나노입자의 평균 직경이 감소하는 경향임을 나타내고 있다.This is because the average diameter of the self-assembled nanoparticles formed from the amphiphilic polyamino acid derivative tends to decrease as the degree of grafting of the hydrophobic polymer, retinoic acid, into the hydrophilic polymer backbone PHEA increases, that is, as the mol% of retinoic acid increases Respectively.
이는 레티노익산의 소수성 인력이 접목도가 증가할수록 강해지면서 더 촘촘한 소수성 도메인을 형성하여 더 작은 입자의 자기조립체가 얻어짐을 의미한다.This means that the hydrophobic attraction of retinoic acid becomes stronger as the degree of grafting increases and forms a more dense hydrophobic domain to obtain self-assembly of smaller particles.
<실험예 3> 자기조립 나노입자 형성에 대한 특성화 분석<Experimental Example 3> Characterization analysis for formation of self-assembled nano-particles
상기 실시예 1 내지 실시예 4에 따라 합성된 양친성 폴리아미노산 유도체(R-PHEA)의 수용액상에서 일어나는 자기조립 나노입자 형성에 대한 특성화 분석을 수행하였다.Characterization analysis for the formation of self-assembled nanoparticles occurring in an aqueous solution of the amphiphilic polyamino acid derivative (R-PHEA) synthesized according to Examples 1 to 4 was carried out.
구체적으로, 도 3을 참조하면, 피렌(pyrene)을 프로브(probe)로 사용하여 임계미셀농도(critical aggregation concentration; 이하 'CAC')를 측정하였다. Specifically, referring to FIG. 3, a critical aggregation concentration (CAC) was measured using pyrene as a probe.
0.0016 mg/㎖에서 1 mg/㎖까지 R-PHEA의 농도를 증가시키면서 피렌을 첨가하여 375 nm 파장에서 여기시켜 방출스펙트럼으로부터 형광 강도 비율(I3/I1)을 R-PHEA 농도에 대하여 플롯하였다.The fluorescence intensity ratio (I 3 / I 1 ) was plotted against the R-PHEA concentration from the emission spectrum by excitation at 375 nm wavelength by adding pyrene while increasing the concentration of R-PHEA from 0.0016 mg / ml to 1 mg / .
낮은 농도에서는 I3/I1가 거의 일정하지만 농도가 증가하면서 I3/I1가 S자 (sigmoidal) 형태로 증가함을 알 수 있다. At low concentrations, I 3 / I 1 is almost constant, but I 3 / I 1 increases in sigmoidal form as the concentration increases.
이것은 피렌 분자의 미세환경 극성도가 감소하기 때문이며, R-PHEA가 수용액상에서 자기조립 나노입자를 형성하기 시작함을 의미한다.This is because the microenvironmental polarity of the pyrene molecules is reduced and R-PHEA starts to form self-assembled nanoparticles in aqueous solution.
따라서 형광강도 비율(I3/I1)에서의 급격한 변화점이 CAC이며, CAC는 회귀직선을 통해 외삽으로 구할 수 있고 두 직선의 교차점을 읽으면 CAC값을 얻게 된다.Therefore, the abrupt change in fluorescence intensity ratio (I 3 / I 1 ) is CAC, CAC can be obtained by extrapolation through the regression line, and the CAC value is obtained when the intersection of two lines is read.
R-PHEA에 대한 CAC 값은, 실시예 1에 따라 합성된 R5-PHEA는 2.5×10-2 mg/㎖이고, 실시예 2에 따라 합성된 R10-PHEA는 1.6×10-2 mg/㎖이고, 또한 실시예 4에 따라 합성된 R30-PHEA는 1.3×10-2 mg/㎖임을 나타내었다.The CAC value for R-PHEA was 2.5 × 10 -2 mg / ml for R5-PHEA synthesized according to Example 1, and 1.6 × 10 -2 mg / ml for R10-PHEA synthesized according to Example 2 , the also synthesized according to example 4 R30-PHEA showed that 1.3 × 10 -2 mg / ㎖.
상기 결과는 레티노익산의 접목도가 증가할수록 CAC는 감소하는 경향을 보여주는데, 이것은 레티노익산의 접목도가 높을수록 자기조립 나노입자를 쉽게 형성할 수 있고 더욱 안정한 자기조립 나노입자를 형성할 수 있음을 나타내는 것이다.The results show that as the degree of grafting of retinoic acid increases, the CAC tends to decrease. This indicates that the higher the degree of grafting of retinoic acid, the easier self-assembled nanoparticles can be formed and more stable self-assembled nanoparticles can be formed .
<실험예 4> 자기조립 나노입자에 레티놀 포집 및 안정적인 전달 여부 확인<Experimental Example 4> Confirmation of retinol trapping and stable delivery to self-assembled nanoparticles
실시예 1 내지 실시예 3에 따라 합성된 양친성 폴리아미노산 유도체(R-PHEA)의 수용액상에서 일어나는 자기조립체 나노입자에 레티놀 포집 및 안정적인 레티놀 전달여부를 확인하기 위해 투과전자현미경(JEM-2010, JEOL Ltd., Japan)을 이용하여 120 kV에서 투과전자현미경 분석(Transmission Electron Microscope; 이하 'TEM')을 수행하였다.To confirm retinol trapping and stable transfer of retinol to self-assembled nanoparticles occurring in an aqueous solution of an amphiphilic polyamino acid derivative (R-PHEA) synthesized according to Examples 1 to 3, a transmission electron microscope (JEM-2010, JEOL Transmission Electron Microscope (hereinafter, referred to as 'TEM') was performed at 120 kV.
R-PHEA로부터 형성된 자기조립 나노입자 형태는 레티노익산 분자의 연속적인 이중 결합의 중심구조로 인한 것으로서, 도 4를 참조하면, TEM 이미지와 같이 레티노익산의 접목도가 상대적으로 낮은 5 mol%(실시예 1), 및 10 mol%(실시예 2)로부터 형성된 자기조립 나노입자는 구 형태의 나노입자가 형성되었음을 확인하였고, 특히 상기 실험예 3에서 확인한 DLS 결과와 마찬가지로 레티노익산의 접목도가 증가할수록 더 작은 자기조립 입자가 형성되는 것을 확인할 수 있었다. The self-assembled nanoparticles formed from R-PHEA are due to the central structure of the continuous double bond of the retinoic acid molecule. Referring to FIG. 4, the TEM image shows that the degree of grafting of retinoic acid is relatively low (5 mol% Example 1), and 10 mol% (Example 2) showed that spherical nanoparticles were formed. Particularly, as in the DLS results obtained in Experimental Example 3, as the degree of grafting of retinoic acid increases It was confirmed that smaller self-assembled particles were formed.
그러나 레티노익산의 접목도가 높은 30 mol%(실시예 4)에서는 바이레이어(bilayer) 또는 멀티레이어(multilayer) 형태의 거대 구조체가 형성된 것을 확인할 수 있었고, 19 mol% 이상에서는 나노입자가 불균일한 형태를 나타내었다.However, it was confirmed that a macromolecular structure of bilayer or multilayer type was formed in 30 mol% (Example 4) having a high degree of grafting of retinoic acid. In the case of 19 mol% or more, Respectively.
이는 이중 결합의 중심 구조로 레티노익산을 접목하여 양친성 폴리아미노산을 합성하였을 때, 판상구조의 영향에 따라 레티놀의 봉입 형태가 달라지므로 접목도에 따라 구조 변화가 일어나기 때문임을 알 수 있다. This is because when the amphiphilic polyamino acid is synthesized by grafting retinoic acid with the central structure of the double bond, the retention pattern of retinol is changed according to the influence of the plate structure, so that the structural change is caused by the grafting degree.
또한, 레티놀 분자를 자기조립 나노입자에 안정하게 포집하였다.In addition, retinol molecules were stably trapped in self-assembled nanoparticles.
구체적으로, 자기조립 나노입자의 내부에 레티놀을 포집할 경우 외부자극이나 환경에 의한 파괴를 막을 수 있기 때문에 효과적인 전달체로 기능성 화장품에 적용할 수 있다.Specifically, when retinol is captured inside the self-assembled nanoparticles, it can be applied to functional cosmetics as an effective delivery vehicle because it can prevent external stimulation or destruction caused by the environment.
도 5는 양친성 폴리아미노산 유도체(R-PHEA)로부터 형성된 자기조립 나노입자로 레티놀 분자를 포집한 주름개선용 조성물의 구조 변화를 나타내고 있다. Fig. 5 shows a structural change of a wrinkle-improving composition obtained by collecting retinol molecules as self-assembled nanoparticles formed from an amphiphilic polyamino acid derivative (R-PHEA).
도 5를 참조하면, 레티놀 분자는 0 내지 30 mol%까지 포집할 수 있으며, 실시예 1과 같이 레티노익산 접목도가 상대적으로 적은 경우, 레티놀 분자가 스스로 자가조립하여 막대구조체를 형성하는 것을 확인하였다(도 5(a) 참조).Referring to FIG. 5, it was confirmed that retinol molecules can be collected up to 0 to 30 mol%, and when the retinoic acid acid grafting degree is relatively low as in Example 1, the retinol molecules self-assemble themselves to form rod structures (See Fig. 5 (a)).
반대로 실시예 4와 같이 상대적으로 접목도가 큰 경우, 거대 구조체 멀티 레이어에 레티놀 분자가 삽입되어 침투됨으로써 멀티 레이어의 구조를 붕괴하는 것을 확인하였다(도 5(c) 참조). On the contrary, when the degree of grafting was relatively large as in Example 4, it was confirmed that the structure of the multilayer collapsed due to penetration of retinol molecules into the macromolecular multilayer (see Fig. 5 (c)).
하지만 실시예 2와 같이 접목도가 10 mol%인 경우 안정적으로 레티놀을 포집하여 구형의 나노입자를 형성하는 것을 확인하였다(도 5(b) 참조). However, when the degree of grafting was 10 mol% as in Example 2, it was confirmed that spherical nanoparticles were formed by stably capturing retinol (see FIG. 5 (b)).
즉, 단순 양친성 폴리아미노산 유도체로 제조한 자기조립 나노입자에서는 볼 수 없었던 내부 봉입 구조를 확인할 수 있고, 레티놀 분자가 자기조립 나노입자 내부에 안정적으로 배열되어 있음을 확인하였으며, 본 발명의 실시예 2와 같은 최적의 접목도를 적용함으로써 레티놀 포집 및 전달의 주름개선제 전달체로 응용할 수 있다.That is, it was confirmed that the self-assembled nanoparticles prepared from the simple amphipathic polyamino acid derivative had an internal encapsulation structure that was not observed and that the retinol molecules were stably arranged in the self-assembled nanoparticles. 2, it can be applied as a delivery agent for wrinkle improving agent for retinol capture and delivery.
이상과 같이, 본 발명은 비록 한정된 실시예와 도면에 의해 설명되었으나, 본 발명은 이것에 의해 한정되지 않으며 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에 의해 본 발명의 기술 사상과 아래에 기재될 청구범위의 균등 범위 내에서 다양한 수정 및 변형이 가능함은 물론이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. It is to be understood that various modifications and changes may be made without departing from the scope of the appended claims.
본 발명은 대한민국 중소기업청의 지원 하에서 과제번호 C0353791에 의해 이루어진 것으로서, 상기 과제의 연구관리전문기관은 중소기업기술정보진흥원, 연구사업명은 "첫걸음기술개발사업", 연구과제명은 "3차원 유-무기 하이브리드 나노소재를 이용한 고기능성 화장품 개발", 주관기관은 숭실대학교 산학협력단, 연구기간은 2015.11.12.~2016.11.11.이다. The present invention was made by the task number C0353791 under the support of the Small and Medium Business Administration of the Republic of Korea. The research management institution of the above-mentioned subject is the Small and Medium Enterprise Technology Information Agency, the research project name is "first step technology development project" Development of High Functional Cosmetics Using Nanomaterials ", and the sponsor organization is Soongsil University Industry-Academic Collaboration Foundation. The research period is November 12, 2015 to November 11, 2016.
Claims (11)
[화학식 1]
상기 화학식 1에서, R1 내지 R2는 서로 상이하고,
수소 또는 하기 화학식 1-1로 표시되는 화합물이며,
[화학식 1-1]
상기 n은 2 내지 600의 정수임.An amphiphilic polyamino acid derivative represented by the following formula (1):
[Chemical Formula 1]
In Formula 1, R 1 to R 2 are different from each other,
Hydrogen or a compound represented by the following formula (1-1)
[Formula 1-1]
And n is an integer of 2 to 600.
상기 양친성 폴리아미노산 유도체는,
폴리숙신이미드(polysuccinimide; 이하 'PSI')를 원료로 하여 얻어진 폴리(2-히드록시에틸 아스파르타마이드)(poly(2-hydroxyethyl aspartamide); 이하 'PHEA')에 화학식 1-1로 표시되는 화합물을 접목시킨 것을 특징으로 하는, 양친성 폴리아미노산 유도체.The method according to claim 1,
The amphiphilic polyamino acid derivative may be,
(2-hydroxyethyl aspartamide; hereinafter referred to as 'PHEA') obtained by using polysuccinimide (hereinafter referred to as 'PSI') as a raw material, Wherein the amphipathic polyamino acid derivative is grafted with a compound.
상기 양친성 폴리아미노산 유도체는,
PHEA에 접목된 화학식 1-1로 표시되는 화합물의 접목도가 5 내지 30 mol%인 것을 특징으로 하는, 양친성 폴리아미노산 유도체.The method of claim 2,
The amphiphilic polyamino acid derivative may be,
The amphiphilic polyamino acid derivative according to claim 1, wherein the degree of grafting of the compound represented by the formula (1-1) grafted to PHEA is 5 to 30 mol%.
상기 조성물은,
화장료 조성물, 약학 조성물 또는 건강기능식품인 것을 특징으로 하는, 주름개선용 조성물.The method of claim 5,
The composition may comprise,
A composition for improving wrinkles characterized by being a cosmetic composition, a pharmaceutical composition or a health functional food.
상기 PHEA에 레티노이드 유도체를 접목시켜 양친성 폴리아미노산 유도체를 합성하는 단계;
상기 합성된 양친성 폴리아미노산 유도체를 수용액에 첨가하여 자기조립 나노입자를 준비하는 단계;
상기 자기조립 나노입자가 형성된 수용액에 레티놀을 첨가하고 혼합한 후 초음파 처리하여 레티놀이 봉입된 주름개선용 조성물을 합성하는 단계;
를 포함하는, 주름개선용 조성물 제조방법.Preparing poly (2-hydroxyethyl aspartamide) (hereinafter referred to as 'PHEA') by reacting polysuccinimide (hereinafter referred to as 'PSI') with ethanolamine ;
Synthesizing an amphiphilic polyamino acid derivative by grafting a retinoid derivative to the PHEA;
Preparing a self-assembled nanoparticle by adding the synthesized amphiphilic polyamino acid derivative to an aqueous solution;
Adding retinol to the aqueous solution in which the self-assembled nanoparticles are formed, mixing and then ultrasonically processing to synthesize a wrinkle-improving composition containing retinol;
By weight based on the total weight of the composition.
상기 레티노이드 유도체는,
레티닐아세티에트, 레티닐팔미테이트, 레티놀, 및 레티노익산으로 이루어진 군에서 선택된 어느 하나인 것을 특징으로 하는, 주름개선용 조성물 제조방법.The method of claim 7,
The retinoid derivative may be,
Wherein the composition is any one selected from the group consisting of retinyl acetyte, retinyl palmitate, retinol, and retinoic acid.
상기 양친성 폴리아미노산 유도체는,
PHEA에 접목된 레티노이드 유도체의 접목도가 5 내지 30 mol%인 것을 특징으로 하는, 주름개선용 조성물 제조방법.The method of claim 7,
The amphiphilic polyamino acid derivative may be,
Wherein the degree of grafting of the retinoid derivative grafted to PHEA is 5 to 30 mol%.
상기 자기조립 나노입자는,
평균 직경이 50 내지 90 nm인 것을 특징으로 하는, 주름개선용 조성물 제조방법.The method of claim 7,
The self-assembled nano-
Wherein the average diameter is 50 to 90 nm.
상기 주름개선용 조성물을 합성하는 단계는,
자기조립 나노입자가 형성된 수용액에 레티놀을 첨가하고 2000 내지 4000 rpm으로 5 내지 10분 동안 혼합한 후 5 내지 15분 동안 초음파 처리하는 것을 특징으로 하는, 주름개선용 조성물 제조방법.The method of claim 7,
The step of synthesizing the composition for wrinkle-
Characterized in that retinol is added to an aqueous solution in which self-assembled nanoparticles are formed, and the mixture is sonicated at 2000 to 4000 rpm for 5 to 10 minutes and then sonicated for 5 to 15 minutes.
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