KR102404209B1 - Liposomes with improved skin permeability and preparation method thereof - Google Patents

Liposomes with improved skin permeability and preparation method thereof Download PDF

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KR102404209B1
KR102404209B1 KR1020210151698A KR20210151698A KR102404209B1 KR 102404209 B1 KR102404209 B1 KR 102404209B1 KR 1020210151698 A KR1020210151698 A KR 1020210151698A KR 20210151698 A KR20210151698 A KR 20210151698A KR 102404209 B1 KR102404209 B1 KR 102404209B1
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liposome
solution
vesicle
present
ceramide
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이호영
김성용
이은자
선동민
이은실
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주식회사 뉴앤뉴
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/342—Alcohols having more than seven atoms in an unbroken chain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/68—Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns

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Abstract

본 발명은 하이드로제네이티드 레시틴 (hydrogenated lechitin), 세틸알코올(cetyl alcohol), 스테아릴알코올(stearyl alcohol), 피토스핑고신(phytosphingosine), 세라마이드NP(ceramideNP)을 사용하여 제조한 리포좀 베지클 및 그 제조방법에 관한 것으로, 본 발명의 리포좀 베지클은 매우 작은 평균크기를 가지고 있어 피부 투과성이 우수하다.The present invention relates to a liposomal vesicle prepared using hydrogenated lechitin, cetyl alcohol, stearyl alcohol, phytosphingosine, and ceramide NP, and its With respect to the manufacturing method, the liposome vesicle of the present invention has a very small average size and thus has excellent skin permeability.

Description

피부 투과성이 향상된 리포좀 베지클 및 이의 제조방법{Liposomes with improved skin permeability and preparation method thereof}Liposomes with improved skin permeability and preparation method thereof

본 발명은 피부 투과성이 향상된 리포좀 베지클 및 이의 제조방법에 관한 것이다.The present invention relates to a liposome vesicle with improved skin permeability and a method for preparing the same.

피부는 피부표면, 표피층, 진피층, 피하조직 등으로 구분할 수 있다. 사람마다 다양한 피부조건들을 가지고 있지만, 이러한 피부들은 외부로부터의 침입을 막는 장벽기능을 수행하고 있다. The skin can be divided into the skin surface, the epidermis, the dermis, and the subcutaneous tissue. Although each person has various skin conditions, these skins perform a barrier function to prevent invasion from the outside.

한편, 피부표면의 각질층은 피부표면에서 각질세포가 납작해지며 형성된다. 이때 15~20층의 각질세포들이 서로 단단하게 결합하여 지방과 단백질로 된 방수 봉인제를 형성시켜 피부내부로 유용물질들이 침입하는 것을 막는다. 따라서, 일반적으로 건강한 피부에서 각질층을 통과하는 것은 쉽게 이루어지지 않으며, 통과된다고 하여도 매우 낮은 농도만 통과되고, 이에 화장료에 포함된 생리활성물질이 그 기능을 충분히 나타내지 못하는 문제점을 가진다.On the other hand, the stratum corneum on the skin surface is formed by flattening the keratinocytes on the skin surface. At this time, the 15-20 layers of keratinocytes are tightly combined with each other to form a waterproof sealant made of fat and protein, preventing useful substances from entering the skin. Therefore, in general, it is not easy to pass through the stratum corneum in healthy skin, and even if it passes, only a very low concentration is passed, and thus, there is a problem in that the physiologically active material contained in the cosmetic does not sufficiently exhibit its function.

이러한 피부 투과 문제를 해결하기 위해 다양한 연구들이 이루어지고 있는데, 대표적인 예로 리포좀구조를 들 수 있다. 리포좀구조는 친수성과 소수성 영역을 모두 가지고 있어서 친수성 및 친유성 물질 모두 구조 내에 포함시킬 수 있는데, 이를 활용하는 경우 화장료의 피부 투과성을 향상시킬 수 있다.Various studies have been made to solve this skin permeation problem, and a representative example is the liposome structure. Since the liposome structure has both hydrophilic and hydrophobic regions, both hydrophilic and lipophilic substances can be included in the structure.

대한민국 등록특허 제10-2020-0006158호(공개일자:2021.07.26)에는, 피부생리활성물질을 함유하는 리포좀 조성물 및 그의 제조방법이 기재되어 있다.Korean Patent Registration No. 10-2020-0006158 (published date: 2021.07.26) describes a liposome composition containing a skin bioactive substance and a method for preparing the same. 대한민국 등록특허 제10-2020-0008642호(공개일자:2021.07.30)에는, 세포 투과도가 향상된 리포좀 및 이를 포함하는 약물전달체가 기재되어 있다.Korean Patent Registration No. 10-2020-0008642 (published date: 2021.07.30) describes a liposome with improved cell permeability and a drug delivery system comprising the same.

본 발명에서는 봉입대상물질의 피부 투과성을 향상시킬 수 있는 리포좀 베지클 및 이의 제조방법을 제공하고자 한다.An object of the present invention is to provide a liposome vesicle capable of improving the skin permeability of a material to be encapsulated, and a method for manufacturing the same.

본 발명은 1차 용액에 2차 용액을 첨가한 후, MCT오일(Medium chain triglycerides)을 추가로 첨가하는 단계 (a); (a) 단계 후, 용액의 온도가 60~70℃가 되도록 가열하며, 호모믹서로 교반시키는 단계 (b); (b) 단계 후, 용액의 온도를 상온까지 식혀 안정화 시키는 단계 (c);를 포함하여 제조하되, 상기 1차 용액은 봉입대상물질, 글리세린(glycerin), 하이드로제네이티드 레시틴 (hydrogenated lechitin)을 혼합시켜 제조한 것이고, 상기 2차 용액은 세틸알코올(cetyl alcohol), 스테아릴알코올(stearyl alcohol), 피토스핑고신(phytosphingosine), 세라마이드NP(ceramideNP)를 혼합한 후 60~70℃가 되도록 가열하여 융해 및 용해시켜 제조한 것임을 특징으로 하는 리포좀 베지클 제조방법을 제공한다.The present invention comprises the steps of adding a second solution to the first solution, and then additionally adding MCT oil (Medium chain triglycerides) (a); After step (a), heating the solution to a temperature of 60 ~ 70 ℃, and stirring with a homomixer (b); After step (b), cooling the temperature of the solution to room temperature to stabilize the solution (c); The second solution was mixed with cetyl alcohol, stearyl alcohol, phytosphingosine, and ceramide NP, and then heated to 60 ~ 70 ° C. It provides a method for preparing a liposome vesicle, characterized in that it is prepared by melting and dissolving.

한편, 본 발명의 리포좀 베지클 제조방법에 있어서, 상기 봉입대상물질은 바람직하게 친수성 물질 또는 친수성 물질이 친수성 용매에 용해되어 있는 것이 좋다.On the other hand, in the method for producing a liposome vesicle of the present invention, the material to be encapsulated is preferably a hydrophilic material or a hydrophilic material is dissolved in a hydrophilic solvent.

한편, 본 발명의 리포좀 베지클 제조방법에 있어서, 상기 단계 (b)의 교반은 바람직하게 3,400~3,600rpm의 속도로 4~6분 동안 교반하는 것이 좋다.On the other hand, in the method for producing a liposome vesicle of the present invention, the stirring in step (b) is preferably stirred at a speed of 3,400 to 3,600 rpm for 4 to 6 minutes.

또한, 본 발명은 상기 리포좀 베지클 제조방법으로 제조한 리포좀 베지클을 제공한다.In addition, the present invention provides a liposome vesicle prepared by the method for preparing the liposome vesicle.

또한, 본 발명은 상기 리포좀 베지클을 함유하는 화장료 조성물을 제공한다.In addition, the present invention provides a cosmetic composition containing the liposome vesicle.

본 발명의 리포좀 베지클은 매우 작은 평균크기를 가지고 있어 피부 투과성이 우수하다. 이를 이용하는 경우 봉입대상물질의 피부 투과성 향상에 사용할 수 있다.The liposome vesicles of the present invention have a very small average size and thus have excellent skin permeability. When using this, it can be used to improve the skin permeability of the material to be encapsulated.

도 1은 본 발명 리포좀 베지클의 크기를 측정한 결과를 보여준다.
도 2는 본 발명 리포좀 베지클을 NTA 장비로 시각화한 사진이다.
도 3은 대조군 리포좀 베지클의 크기를 측정한 결과를 보여준다.
도 4는 본 발명 리포좀 베지클의 zeta potential 측정 결과를 보여준다.
도 5는 대조군 리포좀 베지클의 zeta potential 측정 결과를 보여준다.
도 6은 본 발명 리포좀 베지클 및 대조군 리포좀 베지클의 막투과 확산실험 결과를 보여준다.1 shows the results of measuring the size of the liposome vesicles of the present invention.
Figure 2 is a picture of the visualization of the liposome vesicles of the present invention with NTA equipment.
3 shows the results of measuring the size of the control liposome vesicle.
Figure 4 shows the zeta potential measurement result of the liposome vesicles of the present invention.
5 shows the zeta potential measurement result of the control liposome vesicle.
6 shows the results of the membrane permeation diffusion experiment of the liposome vesicles of the present invention and the control liposome vesicles.

본 발명은 1차 용액에 2차 용액을 첨가한 후, MCT오일(Medium chain triglycerides)을 추가로 첨가하는 단계 (a); (a) 단계 후, 용액의 온도가 60~70℃가 되도록 가열하며, 호모믹서로 교반시키는 단계 (b); (b) 단계 후, 용액의 온도를 상온까지 식혀 안정화 시키는 단계 (c);를 포함하여 제조하되, 상기 1차 용액은 봉입대상물질, 글리세린(glycerin), 하이드로제네이티드 레시틴 (hydrogenated lechitin)을 혼합시켜 제조한 것이고, 상기 2차 용액은 세틸알코올(cetyl alcohol), 스테아릴알코올(stearyl alcohol), 피토스핑고신(phytosphingosine), 세라마이드NP(ceramideNP)를 혼합한 후 60~70℃가 되도록 가열하여 융해 및 용해시켜 제조한 것임을 특징으로 하는 리포좀 베지클 제조방법을 제공한다.The present invention comprises the steps of adding a second solution to the first solution, and then additionally adding MCT oil (Medium chain triglycerides) (a); After step (a), heating the solution to a temperature of 60 ~ 70 ℃, and stirring with a homomixer (b); After step (b), cooling the temperature of the solution to room temperature to stabilize the solution (c); The second solution was mixed with cetyl alcohol, stearyl alcohol, phytosphingosine, and ceramide NP, and then heated to 60 ~ 70 ° C. It provides a method for preparing a liposome vesicle, characterized in that it is prepared by melting and dissolving.

이하, 본 발명의 리포좀 베지클 제조방법에 대해 세분화하여 구체적으로 설명하고자 한다. 하기에서 구체적으로 설명하지 않은 사항은 리포좀 베지클 제조를 위한 당업계에서 널리 알려진 공지 기술들을 활용할 수 있다.Hereinafter, the method for producing a liposome vesicle of the present invention will be subdivided and described in detail. Matters not specifically described below may utilize well-known techniques widely known in the art for preparing liposome vesicles.

< 1차용액 제조 >< Preparation of primary solution >

1차 용액은 봉입대상물질, 글리세린, 하이드로제네이티드 레시틴을 혼합하여 제조한다. The first solution is prepared by mixing the material to be encapsulated, glycerin, and hydrogenated lecithin.

하이드로제네티드 레시틴은 하기 화학식 1의 구조를 가지며, 리포좀 베지클의 지질층을 형성시키는 주요 물질이다.Hydrogenated lecithin has the structure of Chemical Formula 1 below, and is a major substance forming the lipid layer of the liposomal vesicle.

[화학식 1][Formula 1]

하이드로제네티드 레시틴Hydrogenated Lecithin

Figure 112021128037019-pat00001
Figure 112021128037019-pat00001

한편, 본 단계에서 혼합이 더욱 균일하게 이루어 질 수 있도록 교반하는 것이 좋은데, 750~850rpm의 속도로 4~6분간 실시할 수 있다.On the other hand, it is good to stir so that mixing can be made more uniform in this step, and it can be carried out for 4 to 6 minutes at a speed of 750 to 850 rpm.

한편, 본 발명의 리포좀 베지클 제조방법은 친수성 물질을 봉입하는 것이 적합한데, 이에 상기 봉입대상물질은 바람직하게 친수성 물질 또는 친수성 물질이 친수성 용매에 용해되어 있는 것이 좋다. 바람직한 봉입대상물질의 예시로는 열수 추출물, 친수성 유기 용매 추출물, 균주 배양액, 균주 용해물, 균주 여과물이 있다.On the other hand, in the method for preparing a liposome vesicle of the present invention, it is suitable to encapsulate a hydrophilic material, and the encapsulation target material is preferably a hydrophilic material or a hydrophilic material is dissolved in a hydrophilic solvent. Examples of preferred materials to be encapsulated include hot water extract, hydrophilic organic solvent extract, strain culture solution, strain lysate, and strain filtrate.

< 2차 용액 제조 >< Preparation of secondary solution >

2차 용액은 세틸알코올(cetyl alcohol), 스테아릴알코올(stearyl alcohol), 피토스핑고신(phytosphingosine), 세라마이드NP(ceramideNP)를 혼합한 후 60~70℃가 되도록 가열하여 융해 및 용해시켜 제조한다. 세틸알코올, 스테아릴알코올, 피토스핑고신, 세라마이드NP은 상온에서 고체상태로 존재하는데, 이를 서로 혼합시키기 위해 60~70℃가 되도록 가열하여 융해 및 용해시키는 과정이다.The secondary solution is prepared by mixing cetyl alcohol, stearyl alcohol, phytosphingosine, and ceramide NP, and then heating to 60~70℃ to melt and dissolve. . Cetyl alcohol, stearyl alcohol, phytosphingosine, and ceramide NP exist in a solid state at room temperature, and it is a process of melting and dissolving by heating to 60~70℃ to mix them with each other.

세틸알코올 및 스테아릴알코올은 리포좀 베지클 형성시, 계면물질의 분산을 안정화시키기 위해 사용한다.Cetyl alcohol and stearyl alcohol are used to stabilize the dispersion of the interfacial material when forming the liposome vesicle.

피토스핑고신(하기 화학식 2) 및 세라마이드NP(하기 화학식 3)는 리포좀 베지클 제조시 하이드로제네이티드 레시틴과 함께 인지질층을 형성시킨다.Phytosphingosine (Formula 2 below) and ceramide NP (Formula 3 below) form a phospholipid layer together with hydrogenated lecithin when preparing liposome vesicles.

[화학식 2][Formula 2]

피토스핑고신Phytosphingosine

Figure 112021128037019-pat00002
Figure 112021128037019-pat00002

[화학식 3][Formula 3]

세라마이드NPCeramide NP

Figure 112021128037019-pat00003
Figure 112021128037019-pat00003

한편, 세틸알코올 및 스테아릴알코올은 1차 용액에서 첨가한 하이드로제네티드 레시틴을 기준으로 1:1.9 내지 1:2.1 무게비율로 사용하는 것이 좋고, 피토스핑고신 및 세라마이드NP은 1차 용액에서 첨가한 하이드로제네티드 레시틴을 기준으로 1:0.38 내지 1:0.48 무게비율로 사용하는 것이 좋다. 하기 실시예에 따르면, 상기 무게비율로 조성시키는 경우 물질들이 적절하게 분산되며 리포좀 베지클 제조시 석출문제가 발생하지 않게 된다.On the other hand, cetyl alcohol and stearyl alcohol are preferably used in a weight ratio of 1:1.9 to 1:2.1 based on the hydrogenated lecithin added in the first solution, and phytosphingosine and ceramide NP are added in the first solution It is recommended to use it in a weight ratio of 1:0.38 to 1:0.48 based on one hydrogenated lecithin. According to the following examples, when the composition is made in the above weight ratio, the materials are properly dispersed, and the precipitation problem does not occur during the preparation of the liposome vesicle.

< 1차 용액에 2차 용액을 첨가한 후, MCT오일(Medium chain triglycerides)을 추가로 첨가하는 단계 (a) >< After adding the second solution to the first solution, step (a) of additionally adding MCT oil (Medium chain triglycerides) >

본 단계는 리포좀 베지클 형성을 위한 용액을 최종적으로 만드는 단계로, 적절하게 분산되어 있는 1차 용액에 추가 계면 물질 및 분산 안정화제가 있는 2차 용액을 첨가한 후, MCT오일을 최종적으로 넣는 것에 특징이 있다. 이러한 순서를 따라 리포좀 베지클을 제조하는 경우 더욱 작은 리포좀 베지클을 형성시킬 수 있다. This step is a step to finally make a solution for forming a liposome vesicle, and after adding a second solution with an additional interfacial material and a dispersion stabilizer to the properly dispersed first solution, it is characterized by finally adding MCT oil There is this. When preparing a liposomal vesicle in this order, a smaller liposomal vesicle can be formed.

한편, MCT오일은 리포좀의 소수성층에 들어가 리포좀 구조를 안정화 시키는 역할을 하는데, 피부보습에 도움을 준다.On the other hand, MCT oil enters the hydrophobic layer of the liposome and plays a role in stabilizing the liposome structure, which helps to moisturize the skin.

< 용액의 온도가 60~70℃가 되도록 가열하며, 호모믹서로 교반시키는 단계 (b) >< Heating the solution to a temperature of 60 ~ 70 ℃, stirring with a homomixer (b) >

본 단계는 리포좀 베지클을 형성시키는 단계로, 용액의 온도가 60~70℃가 되도록 가열하며, 호모믹서로 교반시키는 것에 특징이 있다. 이때 교반은 바람직하게 3400~3600rpm의 속도로 4~6분동안 교반시키는 것이 좋다. 하기 실험예에 따르면, 상기 조건에서 교반시, 평균 크기가 230~290nm의 리포좀 베지클이 형성된다. This step is a step of forming a liposome vesicle, and is characterized in that the solution is heated to a temperature of 60 to 70° C. and stirred with a homomixer. In this case, the stirring is preferably performed at a speed of 3400 to 3600 rpm for 4 to 6 minutes. According to the following experimental example, upon stirring under the above conditions, liposome vesicles having an average size of 230 to 290 nm are formed.

< 용액의 온도를 상온까지 식혀 안정화 시키는 단계 (c) >< Step of cooling the solution to room temperature to stabilize (c) >

본 단계는 리포좀 베지클이 형성되어 있는 용액의 온도를 상온으로 내려가게 두어 리포좀 베지클을 안정화 시키는 단계이다.This step is a step of stabilizing the liposome vesicle by lowering the temperature of the solution in which the liposome vesicle is formed to room temperature.

한편, 본 발명은 상기 제조방법에 의해 제조된 리포좀 베지클을 제공하는데, 바람직하게 화장료 조성물 형태로 사용하는 것이 좋다. 본 발명의 리포좀 베지클은 피투 투과성이 높아, 기능성 화장료 원료를 봉입시키는 경우 원료의 피부 흡수율이 증가하여 기능성이 더욱 강화된다.On the other hand, the present invention provides a liposome vesicle prepared by the above preparation method, preferably used in the form of a cosmetic composition. The liposome vesicle of the present invention has high blood-to-penetration, and when encapsulating a functional cosmetic raw material, the skin absorption rate of the raw material is increased to further enhance the functionality.

한편, 상기 화장료 조성물의 제형은 사용 방법에 따라 바람직한 형태로 제조될 수 있으며, 일예로는 화장수, 에센스, 로션, 크림, 팩, 파운데이션, 헤어샴푸, 헤어린스, 바디워시, 젤, 스프레이, 폼클렌징, 연고제 등이 될 수 있다.On the other hand, the formulation of the cosmetic composition may be prepared in a preferred form according to the method of use, for example, lotion, essence, lotion, cream, pack, foundation, hair shampoo, hair rinse, body wash, gel, spray, foam cleansing. , an ointment, and the like.

이하, 본 발명의 내용을 하기 실시예 및 실험예를 통하여 보다 상세하게 설명하고자 한다. 다만, 본 발명의 권리범위가 하기 실시예 및 실험예에만 한정되는 것은 아니고 그와 등가의 기술적 사상의 변형까지를 포함한다.Hereinafter, the contents of the present invention will be described in more detail through the following Examples and Experimental Examples. However, the scope of the present invention is not limited to the following examples and experimental examples, but includes modifications of technical ideas equivalent thereto.

[실시예 1: 본 발명의 리포좀 베지클 제조][Example 1: Preparation of liposome vesicles of the present invention]

본 발명의 리포좀 베지클을 제조하고자 했다. 본 발명의 리포좀 베지클 제조방법은 1차 용액 및 2차용액을 혼합한 후 MCT오일(Medium chain triglycerides) 20ml를 첨가하고, 용액의 온도가 65℃가 되도록 가열하며, 호모믹서로 5분간 3500rpm으로 교반하였다. 이후 상온으로 식혀 리포좀 베지클을 완성시켰다.It was intended to prepare a liposome vesicle of the present invention. In the liposome vesicle manufacturing method of the present invention, after mixing the primary solution and the secondary solution, 20 ml of MCT oil (Medium chain triglycerides) is added, the temperature of the solution is heated to 65° C., and the temperature of the solution is 3500 rpm for 5 minutes with a homomixer. stirred. After cooling to room temperature, the liposome vesicle was completed.

1차 용액은 정제수 30ml, 글리세린 40ml, 하이드로제네이티드 레시틴 (hydrogenated lechitin)을 혼합한 후 호모믹서로 5분간 800rpm의 속도로 교반시켜 제조하였다.The first solution was prepared by mixing 30 ml of purified water, 40 ml of glycerin, and hydrogenated lechitin, followed by stirring at a speed of 800 rpm for 5 minutes with a homomixer.

2차 용액은 세틸알코올(cetyl alcohol), 스테아릴알코올(stearyl alcohol), 피토스핑고신(phytosphingosine), 세라마이드NP(ceramideNP)을 혼합한 후 65℃가 되도록 가열 및 교반(300rpm)하여 융해 및 용해시켜 제조하였다.The secondary solution was mixed with cetyl alcohol, stearyl alcohol, phytosphingosine, and ceramide NP, and then melted and dissolved by heating and stirring (300 rpm) to 65 ° C. was prepared.

이때 하이드로제네이티드 레시틴 (hydrogenated lechitin), 세틸알코올(cetyl alcohol), 스테아릴알코올(stearyl alcohol), 피토스핑고신(phytosphingosine), 세라마이드NP(ceramideNP)의 함량비을 달리하여 제조하였는데 자세한 함량은 하기 표 1에 나타내었다. At this time, it was prepared by varying the content ratio of hydrogenated lechitin, cetyl alcohol, stearyl alcohol, phytosphingosine, and ceramide NP. The detailed content is shown in the table below. 1 is shown.

한편, 제조된 리포좀 베지클의 석출 이슈가 있는지 관찰하였는데 그 관찰결과를 하기 표 1에 같이 나타내었다. On the other hand, it was observed whether there is a precipitation issue of the prepared liposome vesicles, and the observation results are shown in Table 1 below.

하이드로제네이티드 레시틴, 세틸알코올, 스테아릴알코올, 피토스핑고신, 세라마이드NP 함량표 및 석출여부 관찰 결과Hydrogenated lecithin, cetyl alcohol, stearyl alcohol, phytosphingosine, ceramide NP content table and precipitation observation result 명칭designation 하이드로제네티드 레시틴 (g)Hydrogenated Lecithin (g) 세틸알코올 (g)Cetyl Alcohol (g) 스테아릴알코올 (g)Stearyl Alcohol (g) 피토스핑고신 (g)Phytosphingosine (g) 세라마이드NP (g)Ceramide NP (g) 석출 발생 여부Whether precipitation occurs 리포좀 1Liposome 1 0.350.35 1.001.00 1.001.00 0.150.15 0.150.15 OO 리포좀 2Liposome 2 0.350.35 0.900.90 0.900.90 0.150.15 0.150.15 OO 리포좀 3Liposome 3 0.350.35 0.800.80 0.800.80 0.150.15 0.150.15 XX 리포좀 4Liposome 4 0.350.35 0.700.70 0.700.70 0.300.30 0.300.30 OO 리포좀 5Liposome 5 0.350.35 0.700.70 0.700.70 0.200.20 0.200.20 OO 리포좀 6Liposome 6 0.350.35 0.700.70 0.700.70 0.150.15 0.150.15 XX 리포좀 7Liposome 7 0.350.35 0.700.70 0.700.70 0.100.10 0.100.10 XX 리포좀 8Liposome 8 0.350.35 0.600.60 0.600.60 0.150.15 0.150.15 OO 리포좀 9Liposome 9 0.350.35 0.350.35 0.350.35 0.150.15 0.150.15 OO 리포좀 10Liposome 10 0.350.35 -- -- -- -- XX

[실험예 1: 본 발명 리포좀 베지클의 크기 확인 실험][Experimental Example 1: Experiment to confirm the size of the liposome vesicles of the present invention]

본 발명 리포좀 베지클의 평균크기를 확인하고자 했다. 이를 위해 실시예 1에서 제조한 리포좀 6의 크기 확인하였는데, 대조군으로는 리포좀 10을 사용하였다. 한편, 크기 측정을 위해 나노 입자 추적 분석 장비 (NTA 장비) 및 zeta potential 측정 장비를 사용하였다.To determine the average size of the liposome vesicles of the present invention. To this end, the size of the liposome 6 prepared in Example 1 was confirmed, and as a control, liposome 10 was used. Meanwhile, for size measurement, nanoparticle tracking analysis equipment (NTA equipment) and zeta potential measurement equipment were used.

도 1은 본 발명 리포좀 베지클의 크기를 측정한 결과를 보여준다.1 shows the results of measuring the size of the liposome vesicles of the present invention.

도 2는 본 발명 리포좀 베지클을 NTA 장비로 시각화한 사진이다.Figure 2 is a picture of the visualization of the liposome vesicles of the present invention with NTA equipment.

도 3은 대조군 리포좀 베지클의 크기를 측정한 결과를 보여준다.3 shows the results of measuring the size of the control liposome vesicle.

도 4는 본 발명 리포좀 베지클의 zeta potential 측정 결과를 보여준다.Figure 4 shows the zeta potential measurement result of the liposome vesicles of the present invention.

도 5는 대조군 리포좀 베지클의 zeta potential 측정 결과를 보여준다.5 shows the zeta potential measurement result of the control liposome vesicle.

도 1, 도 3 내지 도 5의 결과를 보면, 계면물질의 분산을 안정화시키는 세틸알코올, 스테아릴알코올 및 추가계면물질인 피토스핑고신, 세라마이드NP를 추가로 사용하여 제조한 리포좀 6의 경우 평균크기가 작은 것을 확인할 수 있다. 이는 본 발명 리포좀이 더욱 우수한 피부 투과 성능을 가진 것을 의미한다.Referring to the results of FIGS. 1 and 3 to 5 , in the case of liposome 6 prepared by additionally using cetyl alcohol, stearyl alcohol, and additional interface materials phytosphingosine and ceramide NP to stabilize the dispersion of the interfacial material, the average You can see the small size. This means that the liposome of the present invention has more excellent skin penetration performance.

[실험예 2: 본 발명 리포좀 베지클의 투과성 확인 실험][Experimental Example 2: Experiment to confirm the permeability of the liposome vesicles of the present invention]

본 발명 리포좀 베지클의 투과성을 확인하고자 했다. 이를 위해 실시예 1에서 제조한 리포좀 6을 사용하여 막투과 확산실험을 하여 투과 후 잔존하는 외용액의 리포좀 농도를 측정하였다. 대조군으로는 리포좀 10을 사용하였다.It was intended to confirm the permeability of the liposome vesicles of the present invention. To this end, a membrane permeation diffusion test was performed using the liposome 6 prepared in Example 1 to measure the liposome concentration of the external solution remaining after permeation. As a control, liposome 10 was used.

도 6은 본 발명 리포좀 베지클 및 대조군 리포좀 베지클의 막투과 확산실험 결과를 보여준다.6 shows the results of the membrane permeation diffusion experiment of the liposome vesicles of the present invention and the control liposome vesicles.

도 6을 보면, 본 발명 리포좀 베지클의 경우 투과성이 높아 외용액의 농도가 더욱 빠르게 증가하는 것을 확인할 수 있다.6, in the case of the liposome vesicles of the present invention, it can be confirmed that the concentration of the external solution increases more rapidly due to the high permeability.

Claims (5)

1차 용액에 2차 용액을 첨가한 후, MCT오일(Medium chain triglycerides)을 추가로 첨가하는 단계 (a);
(a) 단계 후, 용액의 온도가 60~70℃가 되도록 가열하며, 호모믹서로 교반시키는 단계 (b); 및
(b) 단계 후, 용액의 온도를 상온까지 식혀 안정화 시키는 단계 (c);를 포함하여 리포좀 베지클을 제조하되,
상기 1차 용액은 봉입대상물질, 글리세린(glycerin) 및 하이드로제네이티드 레시틴 (hydrogenated lechitin)을 혼합시켜 제조한 것이고,
상기 2차 용액은 세틸알코올(cetyl alcohol), 스테아릴알코올(stearyl alcohol), 피토스핑고신(phytosphingosine) 및 세라마이드NP(ceramideNP)를 혼합한 후 60~70℃가 되도록 가열하여 융해 및 용해시켜 제조한 것이며,
상기 하이드로제네이티드 레시틴 (hydrogenated lechitin), 상기 세틸알코올(cetyl alcohol), 상기 스테아릴알코올(stearyl alcohol), 상기 피토스핑고신(phytosphingosine) 및 상기 세라마이드NP(ceramideNP)는 각각 1 : 1.9~2.1 : 1.9~2.1 : 0.38~0.48 : 0.38~0.48의 중량비로 사용되고,
상기 리포좀 베지클은 평균 크기가 230~290nm인 것을 특징으로 하는 리포좀 베지클 제조방법.
After adding the second solution to the first solution, MCT oil (Medium chain triglycerides) is further added (a);
After step (a), heating the solution to a temperature of 60 ~ 70 ℃, and stirring with a homomixer (b); and
After step (b), cooling the temperature of the solution to room temperature to stabilize the step (c); to prepare a liposome vesicle, including,
The first solution is prepared by mixing the encapsulation target material, glycerin and hydrogenated lechitin,
The secondary solution is prepared by mixing cetyl alcohol, stearyl alcohol, phytosphingosine and ceramide NP, and then heating to 60 ~ 70 ℃ to melt and dissolve did it,
The hydrogenated lecithin (hydrogenated lechitin), the cetyl alcohol (cetyl alcohol), the stearyl alcohol (stearyl alcohol), the phytosphingosine and the ceramide NP (ceramide NP) are each 1: 1.9 to 2.1: It is used in a weight ratio of 1.9~2.1: 0.38~0.48: 0.38~0.48,
The liposome vesicle manufacturing method, characterized in that the average size of 230 ~ 290nm.
 제1항에 있어서,
상기 봉입대상물질은,
친수성 물질 또는 친수성 물질이 친수성 용매에 용해되어 있는 것을 특징으로 하는 리포좀 베지클 제조방법.
According to claim 1,
The encapsulation target material is
A method for producing a liposome vesicle, characterized in that a hydrophilic substance or a hydrophilic substance is dissolved in a hydrophilic solvent.
 제1항에 있어서,
상기 단계 (b)의 교반은,
3,400~3,600rpm의 속도로 4~6분 동안 교반하는 것을 특징으로 하는 리포좀 베지클 제조방법.
According to claim 1,
The stirring of step (b) is,
A method for producing a liposome vesicle, characterized in that it is stirred for 4 to 6 minutes at a speed of 3,400 to 3,600 rpm.
 제1항의 제조방법으로 제조한 리포좀 베지클.
A liposome vesicle prepared by the method of claim 1.
 제4항의 리포좀 베지클을 함유하는 화장료 조성물.A cosmetic composition comprising the liposomal vesicle of claim 4.
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