KR20230104821A - Method for manufacturing bioactive substance carriers having a multi-layer structure - Google Patents
Method for manufacturing bioactive substance carriers having a multi-layer structure Download PDFInfo
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- KR20230104821A KR20230104821A KR1020230080058A KR20230080058A KR20230104821A KR 20230104821 A KR20230104821 A KR 20230104821A KR 1020230080058 A KR1020230080058 A KR 1020230080058A KR 20230080058 A KR20230080058 A KR 20230080058A KR 20230104821 A KR20230104821 A KR 20230104821A
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- emulsion base
- hydrogenated lecithin
- weight
- parts
- dispersing
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- 238000000034 method Methods 0.000 title claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 16
- 239000000126 substance Substances 0.000 title description 10
- 239000000969 carrier Substances 0.000 title description 3
- 230000000975 bioactive effect Effects 0.000 title 1
- 239000000839 emulsion Substances 0.000 claims abstract description 93
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 88
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 74
- 239000013543 active substance Substances 0.000 claims abstract description 53
- 238000003756 stirring Methods 0.000 claims abstract description 39
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- 150000003904 phospholipids Chemical class 0.000 claims abstract description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000008213 purified water Substances 0.000 claims abstract description 25
- 150000002191 fatty alcohols Chemical class 0.000 claims abstract description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 19
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 19
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- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 5
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 5
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- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 5
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- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 2
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- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 2
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
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- WTFUTSCZYYCBAY-SXBRIOAWSA-N 6-[(E)-C-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-N-hydroxycarbonimidoyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C/C(=N/O)/C1=CC2=C(NC(O2)=O)C=C1 WTFUTSCZYYCBAY-SXBRIOAWSA-N 0.000 description 1
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- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
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- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 1
Classifications
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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
- A61K8/68—Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
-
- 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
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
-
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- 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
- A61Q19/007—Preparations for dry skin
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- 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
- A61K2800/52—Stabilizers
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- 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
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/805—Corresponding aspects not provided for by any of codes A61K2800/81 - A61K2800/95
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- 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
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/83—Electrophoresis; Electrodes; Electrolytic phenomena
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- Oil, Petroleum & Natural Gas (AREA)
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Abstract
본 개시의 일 실시예에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 수소첨가 레시틴을 에탄올에 용해시킨 후, 55-70℃에서 정제수에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 단계, 70-90℃에서 탄소수 12-22의 포화지방알콜을 수소첨가 레시틴 분산액에 투입하면서 교반하여 분산시켜 프리에멀젼베이스를 제조하는 단계, 70-90℃에서 정제수에 프리에멀젼베이스와 수용성물질을 투입하면서 교반하여 분산시켜 에멀젼베이스를 제조하는 단계, 70-90℃에서 에멀젼베이스를 후처리하는 단계 및 70-90℃에서 에멀젼베이스에 오일을 투입하면서 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조하는 단계를 포함한다.In the method for manufacturing a skin active substance delivery system having a multi-layered structure according to an embodiment of the present disclosure, after dissolving hydrogenated lecithin in ethanol, adding the hydrogenated lecithin dissolved in ethanol to purified water at 55-70 ° C. while stirring and dispersing the Preparing a hydrogenated lecithin dispersion, preparing a pre-emulsion base by adding a saturated fatty alcohol having 12 to 22 carbon atoms to the hydrogenated lecithin dispersion while stirring and dispersing at 70-90 ° C, preparing a pre-emulsion base at 70-90 ° C Preparation of an emulsion base by stirring and dispersing while adding an emulsion base and a water-soluble material, post-treatment of the emulsion base at 70-90 ° C, and mixing and dispersing while adding oil to the emulsion base at 70-90 ° C to form a phospholipid bilayer It includes the step of preparing a multi-layer spheroid consisting of.
Description
본 개시는 다층구조를 가지는 피부활성물질 전달체 제조방법에 관한 것으로, 보다 상세하게는 수소첨가 레시틴을 에탄올에 용해시킨 후, 55-70℃에서 정제수에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 단계, 70-90℃에서 탄소수 12-22의 포화지방알콜을 수소첨가 레시틴 분산액에 투입하면서 교반하여 분산시켜 프리에멀젼베이스를 제조하는 단계, 70-90℃에서 정제수에 프리에멀젼베이스와 수용성물질을 투입하면서 교반하여 분산시켜 에멀젼베이스를 제조하는 단계, 70-90℃에서 에멀젼베이스를 후처리하는 단계 및 70-90℃에서 에멀젼베이스에 오일을 투입하면서 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조하는 단계를 포함한다.The present disclosure relates to a method for manufacturing a skin active substance delivery system having a multi-layered structure, and more specifically, after dissolving hydrogenated lecithin in ethanol, adding hydrogenated lecithin dissolved in ethanol to purified water at 55-70 ° C. while stirring Preparing a hydrogenated lecithin dispersion by dispersing, preparing a pre-emulsion base by stirring and dispersing a saturated fatty alcohol having 12 to 22 carbon atoms into the hydrogenated lecithin dispersion at 70-90 ° C, purified water at 70-90 ° C Preparing an emulsion base by stirring and dispersing while adding a pre-emulsion base and a water-soluble material, post-processing the emulsion base at 70-90 ° C, and dispersing by stirring while adding oil to the emulsion base at 70-90 ° C and preparing multilayer spherules composed of phospholipid bilayers.
화장품 산업에서 주름 개선 성분으로 알려진 올레아놀릭산(Oleanolic acid)과 같은 유효성분은 물에 거의 녹지 않는 난용성일 뿐만 아니라 제형에 적용하여도 안정도 및 역가 불안정 문제로 인하여 일정 함량이상 포함하는데 한계가 있다. 특히, 물의 함량이 많은 가용화 제형에서의 적용은 힘들며 제형 내 안정도를 확보하는데 큰 어려움이 있다.Active ingredients such as oleanolic acid, known as a wrinkle-improving ingredient in the cosmetic industry, are not only poorly soluble in water, but also have limitations in containing more than a certain amount due to stability and potency instability problems even when applied to formulations. In particular, it is difficult to apply in a solubilized formulation with a high water content, and it is difficult to secure stability in the formulation.
또한, 생물학적 세포막과 유사한 리포솜은 양친매성으로 이루어져, 친수성/친유성 물질과 모두 친화력이 우수하여 생체 친화적인 담체로 약물 전달 분야에 많이 활용되어 왔던 기술이다. 이 기술은 최근 화장품 산업에서도 난용성 효능 물질 안정화 및 피부 흡수 촉진 매개체 등으로 다양한 제형으로 연구되고 있었다. 피부에 적용하는 제형으로 만들기 위해서는 효율적인 피부 투과 및 흡수를 위하여 입자 크기 제어 등 리포솜의 특성을 잘 이해해야 하며 리포솜을 형성할 수 있는 조건을 최적화할 필요가 요구된다.In addition, liposomes, which are similar to biological cell membranes, are amphiphilic and have excellent affinity with both hydrophilic and lipophilic substances, and thus have been widely used in the field of drug delivery as biocompatible carriers. This technology has recently been studied in various formulations in the cosmetics industry as a medium for stabilizing poorly soluble active substances and promoting skin absorption. In order to make a formulation to be applied to the skin, it is necessary to understand the characteristics of liposomes, such as particle size control, for efficient skin penetration and absorption, and to optimize the conditions for forming liposomes.
상기와 같은 문제점을 해결하기 위해, 본 개시의 다층구조를 가지는 피부활성물질 전달체 제조방법은 수소첨가 레시틴을 에탄올에 용해시킨 후, 55-70℃에서 정제수에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 단계, 70-90℃에서 탄소수 12-22의 포화지방알콜을 수소첨가 레시틴 분산액에 투입하면서 교반하여 분산시켜 프리에멀젼베이스를 제조하는 단계, 70-90℃에서 정제수에 프리에멀젼베이스와 수용성물질을 투입하면서 교반하여 분산시켜 에멀젼베이스를 제조하는 단계, 70-90℃에서 에멀젼베이스를 후처리하는 단계 및 70-90℃에서 에멀젼베이스에 오일을 투입하면서 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조하는 단계를 포함한다.In order to solve the above problems, the method for manufacturing a skin active substance delivery system having a multi-layered structure of the present disclosure is to dissolve hydrogenated lecithin in ethanol, and then inject hydrogenated lecithin dissolved in ethanol into purified water at 55-70 ° C. Preparing a hydrogenated lecithin dispersion by stirring and dispersing, preparing a pre-emulsion base by stirring and dispersing while adding a saturated fatty alcohol having 12 to 22 carbon atoms to the hydrogenated lecithin dispersion at 70-90 ° C, 70-90 ° C Preparing an emulsion base by stirring and dispersing while adding a pre-emulsion base and a water-soluble substance to purified water, post-processing the emulsion base at 70-90 ° C, and stirring while adding oil to the emulsion base at 70-90 ° C and dispersing to prepare multilayer spherules composed of phospholipid bilayers.
본 개시의 일 실시예에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 수소첨가 레시틴을 에탄올에 용해시킨 후, 55-70℃에서 정제수에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 단계, 70-90℃에서 탄소수 12-22의 포화지방알콜을 수소첨가 레시틴 분산액에 투입하면서 교반하여 분산시켜 프리에멀젼베이스를 제조하는 단계, 70-90℃에서 정제수에 프리에멀젼베이스와 수용성물질을 투입하면서 교반하여 분산시켜 에멀젼베이스를 제조하는 단계, 70-90℃에서 에멀젼베이스를 후처리하는 단계 및 70-90℃에서 에멀젼베이스에 오일을 투입하면서 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조하는 단계를 포함한다.In the method for manufacturing a skin active substance delivery system having a multi-layered structure according to an embodiment of the present disclosure, after dissolving hydrogenated lecithin in ethanol, adding the hydrogenated lecithin dissolved in ethanol to purified water at 55-70 ° C. while stirring and dispersing the Preparing a hydrogenated lecithin dispersion, preparing a pre-emulsion base by adding a saturated fatty alcohol having 12 to 22 carbon atoms to the hydrogenated lecithin dispersion while stirring and dispersing at 70-90 ° C, preparing a pre-emulsion base at 70-90 ° C Preparation of an emulsion base by stirring and dispersing while adding an emulsion base and a water-soluble material, post-treatment of the emulsion base at 70-90 ° C, and mixing and dispersing while adding oil to the emulsion base at 70-90 ° C to form a phospholipid bilayer It includes the step of preparing a multi-layer spheroid consisting of.
본 개시의 일 실시예에 따른 에멀젼베이스를 후처리하는 단계는 에멀젼베이스의 평균입자를 90㎚ 이하로 필터링하고, 전극 배열법을 통해 판상 구조로 형성되는 것을 특징으로 한다.The step of post-processing the emulsion base according to an embodiment of the present disclosure is characterized in that the average particle of the emulsion base is filtered to 90 nm or less, and formed into a plate-like structure through an electrode arrangement method.
본 개시의 일 실시예에 따른 포화지방알콜에는 세라마이드, 스테롤 또는 탄소수 12-22의 포화지방산 중 어느 하나 이상이 추가로 첨가되는 것을 특징으로 한다.The saturated fatty alcohol according to an embodiment of the present disclosure is characterized in that at least one of ceramide, sterol, or saturated fatty acid having 12 to 22 carbon atoms is additionally added.
본 개시의 일 실시예에 따른 수용성물질은 수용성피부활성물질이고, 오일은 유용성피부활성물질이고, 수용성피부활성물질이 인지질이중층 사이에 위치하면, 유용성피부활성물질은 인지질이중층 내에 위치하고, 수용성피부활성물질이 인지질이중층 내에 위치하면, 유용성피부활성물질은 인지질이중층 사이에 위치하는 것을 특징으로 한다.According to an embodiment of the present disclosure, the water-soluble skin-active substance is a water-soluble skin-active substance, oil is an oil-soluble skin-active substance, and when the water-soluble skin-active substance is located between the phospholipid bilayers, the oil-soluble skin-active substance is located within the phospholipid bilayer, and the water-soluble skin-active substance When the substance is located within the phospholipid bilayer, the oil-soluble skin active substance is located between the phospholipid bilayers.
본 개시의 일 실시예에 따른 수소첨가 레시틴 분산액은 수소첨가 레시틴 10-30 중량부, 에탄올 5-10 중량부를 이용하여 제조되며, 프리에멀젼베이스는 정제수 30-75 중량부, 수소첨가 레시틴 분산액 20 중량부, 탄소수 12-22의 포화지방알콜 15-40 중량부를 이용하여 제조되며, 에멀젼베이스는 정제수 30-75 중량부, 프리에멀젼베이스 15-40 중량부와 수용성물질 10-30 중량부를 이용하여 제조되며, 인지질이중층으로 이루어진 다층소구체는 에멀젼베이스 30-75 중량부에 오일 5-25 중량부를 이용하여 제조되는 것을 특징으로 한다.The hydrogenated lecithin dispersion according to an embodiment of the present disclosure is prepared using 10-30 parts by weight of hydrogenated lecithin and 5-10 parts by weight of ethanol, and the pre-emulsion base is 30-75 parts by weight of purified water and 20 parts by weight of hydrogenated lecithin dispersion. It is prepared using 15-40 parts by weight of a saturated fatty alcohol having 12-22 carbon atoms, and the emulsion base is prepared using 30-75 parts by weight of purified water, 15-40 parts by weight of a pre-emulsion base and 10-30 parts by weight of a water-soluble material. , Multilayer spherules composed of phospholipid bilayers are characterized in that they are prepared using 5-25 parts by weight of oil in 30-75 parts by weight of emulsion base.
본 개시에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 구형의 안정한 리포좀 구조가 유연하게 피부의 좁은 틈을 통과하는 것이 가능하여 피부의 진피층까지 전달체의 파손없이 영양분 등의 활성물질을 안정적으로 전달하는 효과를 갖는다.The method for manufacturing a skin active substance delivery system having a multi-layered structure according to the present disclosure enables the stable spherical liposome structure to pass through narrow gaps in the skin flexibly, stably delivering active substances such as nutrients to the dermal layer of the skin without damage to the delivery system. has the effect of
본 개시에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 인지질이중층으로 된 다층구조를 가짐으로써, 피부의 각층에 유용성 피부활성물질, 수용성 피부활성물질 또는 난용성 피부활성물질을 각각 전달할 수 있는 효과를 갖는다.The method for manufacturing a skin active substance delivery system having a multi-layered structure according to the present disclosure has a multi-layered structure of phospholipid bilayers, so that each layer of the skin can deliver an oil-soluble skin-active substance, a water-soluble skin-active substance, or a sparingly-soluble skin-active substance, respectively. have
본 개시에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 공정 시간을 절약하고, 최적의 중량부를 제공하는 공정으로 인지질이중층으로 이루어진 안정적인 다층구조를 가지는 피부활성물질 전달체를 경제적으로 제조할 수 있는 효과를 갖는다.The method for manufacturing a skin active substance delivery system having a multilayer structure according to the present disclosure is a process that saves process time and provides an optimal weight part, and has an effect of economically manufacturing a skin active substance delivery system having a stable multilayer structure composed of phospholipid bilayers. have
본 개시에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 시간이 경과함에도 인지질이중층으로 이루어진 다층소구체가 안정적으로 유지되므로 피부의 여러 조직을 통과하면서 피부의 각층에 유용성 피부활성물질, 수용성 피부활성물질 또는 난용성 피부활성물질을 안정적으로 전달할 수 있는 효과를 갖는다.The method for manufacturing a skin-active substance delivery system having a multi-layered structure according to the present disclosure maintains stable multi-layered spherules composed of phospholipid bilayers over time, so that useful skin-active substances and water-soluble skin-active substances can be obtained in each layer of the skin while passing through various tissues of the skin. It has the effect of stably delivering substances or poorly soluble skin active substances.
본 개시에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 용해 포화도가 향상된 균일한 크기의 오일 입자를 제공해서 분산안정성이 높은 다층구조를 가지는 피부활성물질 전달체를 제공하는 효과를 갖는다.The method for preparing a skin active substance delivery system having a multi-layer structure according to the present disclosure has an effect of providing a skin active substance delivery system having a multi-layer structure with high dispersion stability by providing oil particles of uniform size with improved solubility saturation.
본 개시의 효과는 이상에서 언급한 효과로 제한되지 않으며, 언급되지 않은 다른 효과들은 청구범위의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.Effects of the present disclosure are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description of the claims.
이하, 본 개시의 실시를 위한 구체적인 내용을 상세히 설명한다. 다만, 이하의 설명에서는 본 개시의 요지를 불필요하게 흐릴 우려가 있는 경우, 널리 알려진 기능이나 구성에 관한 구체적 설명은 생략하기로 한다.Hereinafter, specific details for the implementation of the present disclosure will be described in detail. However, in the following description, if there is a risk of unnecessarily obscuring the gist of the present disclosure, detailed descriptions of well-known functions or configurations will be omitted.
본 명세서에서 사용되는 용어에 대해 간략히 설명하고, 개시된 실시예에 대해 구체적으로 설명하기로 한다. 본 명세서에서 사용되는 용어는 본 개시에서의 기능을 고려하면서 가능한 현재 널리 사용되는 일반적인 용어들을 선택하였으나, 이는 관련 분야에 종사하는 기술자의 의도 또는 판례, 새로운 기술의 출현 등에 따라 달라질 수 있다. 또한, 특정한 경우는 출원인이 임의로 선정한 용어도 있으며, 이 경우 해당되는 발명의 설명 부분에서 상세히 그 의미를 기재할 것이다. 따라서 본 개시에서 사용되는 용어는 단순한 용어의 명칭이 아닌, 그 용어가 가지는 의미와 본 개시의 전반에 걸친 내용을 토대로 정의되어야 한다.Terms used in this specification will be briefly described, and the disclosed embodiments will be described in detail. The terms used in this specification have been selected from general terms that are currently widely used as much as possible while considering the functions in the present disclosure, but they may vary according to the intention of a person skilled in the related field, a precedent, or the emergence of new technology. In addition, in a specific case, there is also a term arbitrarily selected by the applicant, and in this case, the meaning will be described in detail in the description of the invention. Therefore, terms used in the present disclosure should be defined based on the meaning of the term and the general content of the present disclosure, not simply the name of the term.
본 명세서에서의 단수의 표현은 문맥상 명백하게 단수인 것으로 특정하지 않는 한, 복수의 표현을 포함한다. 또한, 복수의 표현은 문맥상 명백하게 복수인 것으로 특정하지 않는 한, 단수의 표현을 포함한다.Expressions in the singular number in this specification include plural expressions unless the context clearly dictates that they are singular. Also, plural expressions include singular expressions unless the context clearly specifies that they are plural.
본원 명세서 전체에서, 어떤 부분이 어떤 구성 요소를 "포함"한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성 요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.Throughout the present specification, when a certain component is said to "include", it means that it may further include other components without excluding other components unless otherwise stated.
본원 명세서 전체에서 사용되는 정도의 용어 "약", "실질적으로" 등은 허용오차가 존재할 때 허용오차를 포괄하는 의미로 사용된 것이다.The terms "about," "substantially," and the like used throughout this specification are intended to encompass tolerances when such tolerances exist.
본원 명세서 전체에서, 마쿠시 형식의 표현에 포함된 "이들의 조합(들)"의 용어는 마쿠시 형식의 표현에 기재된 구성 요소들로 이루어진 군에서 선택되는 하나 이상의 혼합 또는 조합을 의미한다.Throughout this specification, the term "combination(s) of these" included in the expression of the Markush form means a mixture or combination of one or more selected from the group consisting of the constituent elements described in the expression of the Markush form.
본원 명세서 전체에서, "A 및/또는 B"의 기재는 "A, 또는 B, 또는 A 및 B"를 의미한다.Throughout this specification, reference to "A and/or B" means "A, or B, or A and B".
아래에서는 본원이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본원의 실시예를 상세히 설명한다. 그러나 본원은 여러 가지 상이한 형태로 구현될 수 있으며 여기에서 설명하는 실시예에 한정되지 않는다.Hereinafter, embodiments of the present disclosure will be described in detail so that those skilled in the art can easily practice them. However, the present disclosure may be implemented in many different forms and is not limited to the embodiments described herein.
본 개시의 일 실시예에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 수소첨가 레시틴을 에탄올에 용해시킨 후, 55-70℃에서 정제수에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 단계, 70-90℃에서 탄소수 12-22의 포화지방알콜을 수소첨가 레시틴 분산액에 투입하면서 교반하여 분산시켜 프리에멀젼베이스를 제조하는 단계, 70-90℃에서 정제수에 프리에멀젼베이스와 수용성물질을 투입하면서 교반하여 분산시켜 에멀젼베이스를 제조하는 단계, 70-90℃에서 에멀젼베이스를 후처리하는 단계 및 70-90℃에서 에멀젼베이스에 오일을 투입하면서 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조하는 단계를 포함한다.In the method for manufacturing a skin active substance delivery system having a multi-layered structure according to an embodiment of the present disclosure, after dissolving hydrogenated lecithin in ethanol, adding the hydrogenated lecithin dissolved in ethanol to purified water at 55-70 ° C. while stirring and dispersing the Preparing a hydrogenated lecithin dispersion, preparing a pre-emulsion base by adding a saturated fatty alcohol having 12 to 22 carbon atoms to the hydrogenated lecithin dispersion while stirring and dispersing at 70-90 ° C, preparing a pre-emulsion base at 70-90 ° C Preparation of an emulsion base by stirring and dispersing while adding an emulsion base and a water-soluble material, post-treatment of the emulsion base at 70-90 ° C, and mixing and dispersing while adding oil to the emulsion base at 70-90 ° C to form a phospholipid bilayer It includes the step of preparing a multi-layer spheroid consisting of.
본 개시에 따른 수소첨가 레시틴 분산액을 제조하는 단계는 수소첨가 레시틴 10-30 중량부를 에탄올 5-10 중량부에 먼저 용해시킨 후, 55-70℃의 정제수에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 800-1000rpm 조건에서 8-12분 동안(바람직하게는 10분 동안) 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조한다.In the step of preparing a hydrogenated lecithin dispersion according to the present disclosure, 10-30 parts by weight of hydrogenated lecithin is first dissolved in 5-10 parts by weight of ethanol, and then the hydrogenated lecithin dissolved in ethanol is added to purified water at 55-70 ° C. Hydrogenated lecithin dispersion is prepared by stirring and dispersing for 8-12 minutes (preferably for 10 minutes) under the conditions of an AGI MIXER (general mixing mixer) rotational speed of 800-1000 rpm.
55-70℃에서 수소첨가 레시틴을 에탄올 5-10 중량부에 용해시키는 전처리 과정을 거침으로써 수소첨가 레시틴이 고온에서 변성될 가능성을 방지하고, 에탄올이 피부투과 증진제 역할을 하기 때문에, 피부 각질세포 사이의 정돈된 지질층에 에탄올이 접근하면 지질분자의 극성부분과 작용하여 각질층 지질의 전이온도(Transition temperature)를 낮추고 피부 지질층의 유동성을 증대시켜 지질구조를 느슨하게 만들어 투과성이 높아질 수 있도록 구조적 변형이 발생하며 유연한 막을 가진 인지질이중층으로 이루어진 다층소구체의 구조적 변형이 쉽게 이루어져 피부 침투가 용이해진다.By going through a pretreatment process of dissolving hydrogenated lecithin in 5-10 parts by weight of ethanol at 55-70 ° C, the possibility of hydrogenated lecithin being denatured at high temperatures is prevented, and since ethanol acts as a skin permeation enhancer, When ethanol approaches the ordered lipid layer, it acts with the polar part of the lipid molecule to lower the transition temperature of the lipids in the stratum corneum and increase the fluidity of the lipid layer of the skin, thereby loosening the lipid structure and causing structural transformation to increase permeability. Structural transformation of multilayer globules composed of phospholipid bilayers with flexible membranes is easily performed, thereby facilitating skin penetration.
또한, 에멀젼베이스에 오일을 투입해서 인지질이중층으로 이루어진 다층소구체를 제조하는 단계에서 5 미만 중량부의 에탄올을 이용하는 경우에 다층소구체의 입자 크기가 매우 작고, 오일의 용해도가 감소하는 문제를 가지고, 10 초과 중량부의 에탄올을 이용하는 경우에는 10 미만 중량부의 에탄올을 이용하는 경우와 비교해서 입자 크기 및 오일의 용해도가 에탄올 중량부에 비례해서 증가하지 않고 제한적이기 때문에 에탄올 5-10 중량부를 이용함으로써 다층소구체의 입자를 안정한 상태로 유지하고 최적의 오일 용해도를 제공한다.In addition, in the case of using less than 5 parts by weight of ethanol in the step of preparing multilayer spherules composed of phospholipid bilayers by adding oil to the emulsion base, the particle size of the multilayer spherules is very small and the solubility of oil is reduced. When using more than 10 parts by weight of ethanol, compared to the case of using less than 10 parts by weight of ethanol, the particle size and solubility of oil do not increase in proportion to parts by weight of ethanol and are limited. of particles in a stable state and provide optimal oil solubility.
본 개시에 따른 프리에멀젼베이스를 제조하는 단계는 70-90℃에서 탄소수 12-22의 포화지방알콜 15-40 중량부에 수소첨가 레시틴 분산액 20 중량부 및 정제수 30-75 중량부를 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 800-1000rpm 조건에서 8-12분 동안(바람직하게는 10분 동안) 교반하여 분산시켜 프리에멀젼베이스를 제조한다.The step of preparing a pre-emulsion base according to the present disclosure is performed by adding 20 parts by weight of hydrogenated lecithin dispersion and 30-75 parts by weight of purified water to 15 to 40 parts by weight of a saturated fatty alcohol having 12 to 22 carbon atoms at 70 to 90 ° C. General mixing mixer) Prepare a pre-emulsion base by stirring and dispersing for 8-12 minutes (preferably for 10 minutes) at a rotational speed of 800-1000 rpm.
본 개시에 따른 수소첨가 레시틴은 높은 계면장력으로 인해 장시간의 안정성을 확보하기 어렵기 때문에, 수소첨가 레시틴의 계면장력을 낮추어 줄 수 있는 시스템이 필요하다. 이러한 레시틴의 높은 계면장력을 낮추어 주고 장시간의 안정성 확보를 위한 최적의 조합이 수소첨가 레시틴 분산액 20 중량부와 탄소수 12-22의 포화지방알콜 15-40 중량부의 조합이다.Since it is difficult to secure long-term stability of the hydrogenated lecithin according to the present disclosure due to high interfacial tension, a system capable of lowering the interfacial tension of the hydrogenated lecithin is required. An optimal combination for lowering the high interfacial tension of lecithin and securing long-term stability is a combination of 20 parts by weight of a hydrogenated lecithin dispersion and 15-40 parts by weight of a saturated fatty alcohol having 12 to 22 carbon atoms.
일반적으로 지방알콜 또는 지방산은 유화의 형성과 형성된 유화의 안정화에 도움을 주는 성분으로 전기적 반발, 점도의 변경, 유화막에 필름 형성 등의 기전으로 에멀젼끼리 합체하는 것을 막아주거나 감소시켜 주어 제품의 안전성(Stability)를 높여 주기 때문에, 수소첨가 레시틴의 계면장력을 낮추어 장시간 안정성을 확보하기 위한 유화안정제로 이용된다.In general, fatty alcohols or fatty acids are ingredients that help in the formation of emulsions and stabilization of the formed emulsions. They prevent or reduce the coalescence of emulsions through mechanisms such as electrical repulsion, change in viscosity, and film formation on emulsion films, thereby improving product safety. Because it increases stability, it is used as an emulsion stabilizer to secure long-term stability by lowering the interfacial tension of hydrogenated lecithin.
본 개시에 따른 포화지방알콜은 포화지방알콜을 구성하는 탄소의 수가 증가하면 유화한 제품의 점도는 증가하게 되는데, 탄소의 수가 22 이상이 되면 오히려 점도가 감소하는 결과가 나타나고, 12 이하의 탄소수를 가진 포화지방알콜은 탄소사슬의 길이가 짧기 때문에 전달체(Vehicle)의 기본 구조인 이중막(인지질이중층) 구조를 형성하기 어렵고, 비록 생성되었다 하더라도 형성된 전달체(Vehicle)의 안정성이 떨어지기 때문에, 탄소 수가 12-22인 포화지방알콜을 혼합하여 유화한 제품의 점도를 조절하고, 안정성을 확보하는 효과를 갖는다.In the saturated fatty alcohol according to the present disclosure, when the number of carbons constituting the saturated fatty alcohol increases, the viscosity of the emulsified product increases. When the number of carbons is 22 or more, the viscosity decreases. Since the length of the carbon chain of saturated fatty alcohol is short, it is difficult to form a double membrane (phospholipid bilayer) structure, which is the basic structure of a vehicle, and even if it is produced, the stability of the formed vehicle is low. It has the effect of adjusting the viscosity of emulsified products by mixing 12-22 saturated fatty alcohol and securing stability.
본 개시의 일 실시예에 따른 포화지방알콜에는 세라마이드, 스테롤, 탄소수 12-22의 포화지방산 중 어느 하나 이상이 추가로 첨가되는 것을 특징으로 한다.Saturated fatty alcohol according to an embodiment of the present disclosure is characterized in that at least one of ceramide, sterol, and saturated fatty acid having 12 to 22 carbon atoms is additionally added.
세라마이드, 스테롤 또는 탄소수 12-22의 포화지방산이 추가되는 양만큼 탄소수 12-22의 포화지방알콜은 감소되어야 한다. Saturated fatty alcohols with 12 to 22 carbon atoms should be reduced by the amount that ceramides, sterols or saturated fatty acids with 12 to 22 carbon atoms are added.
세라마이드, 스테롤 또는 탄소수 12-22의 포화지방산이 과다하게 첨가되면 불안정한 판상미셀 구조가 안정화되는 효과 외에 판상미셀이 다층구조를 이루기 전에 양말단이 먼저 연결되어 구형 모양을 이루는 문제가 발생할 수 있다.When ceramide, sterol, or saturated fatty acid having 12 to 22 carbon atoms is added excessively, in addition to the effect of stabilizing the unstable plate-like micelle structure, a problem of forming a spherical shape by first connecting both ends before forming a multi-layered structure of the plate-like micelle may occur.
포화지방알콜을 구성하는 탄소 수가 증가함에 따라 유화 제품의 점도 증가의 문제를 해결하기 위해 탄소수 12-22의 포화지방산이 추가로 포함될 수 있다. 첨가되는 포화지방산의 탄소수가 12-22인 이유는 12-22의 탄소수를 가지는 포화지방알콜을 사용하였기에 서로 상용성을 높일 수 있기 때문이다.As the number of carbon atoms constituting the saturated fatty alcohol increases, saturated fatty acids having 12 to 22 carbon atoms may be additionally included to solve the problem of increasing the viscosity of the emulsified product. The reason why the added saturated fatty acids have 12-22 carbon atoms is that compatibility with each other can be enhanced because saturated fatty alcohols having 12-22 carbon atoms are used.
본 개시에 따른 세라마이드와 스테롤의 역할은 수소첨가 레시틴의 입자가 잘 배열되어 만들어주며, 인지질이중층으로 된 이중막 구조의 수소첨가 레시틴 입자들 사이에 존재하여 이중막 구조의 막을 좀 더 촘촘하게 만들어 주어 다층구조를 가지는 피부활성물질 전달체의 안정성을 향상시켜 주는 작용을 한다.The role of ceramide and sterol according to the present disclosure is to make the hydrogenated lecithin particles well arranged, and exist between hydrogenated lecithin particles of a double membrane structure with a phospholipid bilayer to make the membrane of the double membrane structure more dense. It acts to improve the stability of the skin active substance delivery system having a structure.
본 개시에 따른 세라마이드와 스테롤은 피부 세포 가운데 표피 각질층의 지질막 성분의 하나로 피부 표면에서 손실되는 수분을 방어하고 외부로부터 유해 물질의 침투를 막는 역할을 하는 물질이다. 세라마이드는 구조적으로 수분과 결합하여 지질층 장벽의 역할을 수행하며 외부 환경 및 미생물로부터 신체를 방어하며 생리학적으로는 신호시스템으로 세포의 성장을 조절해 주는 기능을 가지고 있다.Ceramides and sterols according to the present disclosure are one of the lipid film components of the stratum corneum of the epidermis among skin cells and are substances that play a role in protecting moisture lost from the skin surface and preventing the penetration of harmful substances from the outside. Ceramide functions as a lipid layer barrier by structurally combining with water, defends the body from the external environment and microorganisms, and physiologically controls cell growth as a signaling system.
본 개시에 따른 에멀젼베이스를 제조하는 단계는 70-90℃에서 정제수 30-75 중량부에 프리에멀젼베이스 15-40 중량부와 수용성물질 10-30 중량부를 투입하면서 교반하여 분산시켜 제조한다.The step of preparing an emulsion base according to the present disclosure is prepared by adding 15-40 parts by weight of a pre-emulsion base and 10-30 parts by weight of a water-soluble material to 30-75 parts by weight of purified water at 70-90 ° C. while stirring and dispersing.
정제수에 70-90℃로 가온된 프리에멀젼베이스 15-40 중량부와 수용성물질 10-30 중량부를 서서히 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 800-1000rpm 조건에서 8-12분 동안(바람직하게는 10분 동안) 교반시켜 제조된 에멀젼베이스는 판상미셀이 수용성물질에 의해 길게 연장되고 다층의 구조를 가진다. 판상미셀이 수용성물질에 의해 길게 연장되고 다층 구조를 가짐으로써, 다층소구체가 용이하게 형성될 수 있는 준비가 완료된 효과를 가진다. While gradually adding 15-40 parts by weight of the pre-emulsion base heated to 70-90 ℃ and 10-30 parts by weight of water-soluble material in purified water, AGI MIXER (general mixing mixer) for 8-12 minutes (preferably for 10 minutes), the emulsion base prepared by stirring has a structure in which plate-like micelles are elongated by water-soluble substances and have a multi-layered structure. Since the plate-shaped micelles are elongated by the water-soluble material and have a multi-layered structure, multi-layered spherules can be easily formed.
본 개시에 따른 에멀젼베이스를 후처리하는 단계는 에멀젼베이스의 평균입자를 90㎚ 이하로 필터링하고, 전극 배열법을 통해 판상 구조로 형성되는 것을 특징으로 한다.The step of post-processing the emulsion base according to the present disclosure is characterized in that the average particle of the emulsion base is filtered to 90 nm or less and formed into a plate-like structure through an electrode arrangement method.
종래 기술의 에멀젼베이스는 내부 물질들이 너무 융합되어 오히려 반발하게 되어 판상 구조의 형태가 제대로 형성되지 않는 문제가 발생한다.The emulsion base of the prior art has a problem in that the shape of the plate-like structure is not properly formed because the internal materials are too fused and rather repelled.
본 개시에 따른 에멀젼베이스는 90㎚ 필터 마이크론 여과지를 통해 90㎚ 이하로 균일하게 필터링하고, 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공해서 에멀젼베이스 내부에 유사한 액상들의 융합을 향상시켜서 에멀젼베이스가 판상 구조를 길고 안정적인 형태를 가질 수 있도록 한다. The emulsion base according to the present disclosure is uniformly filtered to 90 nm or less through a 90 nm filter micron filter paper, and the filtered emulsion base is placed between the top / bottom electrodes to provide a monopolar charge to fuse similar liquid phases inside the emulsion base is improved so that the emulsion base can have a long and stable form of the plate-like structure.
본 개시에 따른 인지질이중층으로 이루어진 다층소구체를 제조하는 단계는 70-90℃에서 에멀젼베이스에 오일을 투입하면서 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조한다.In the step of preparing multilayer spherules composed of phospholipid bilayers according to the present disclosure, oil is added to the emulsion base at 70-90° C. while stirring and dispersing to prepare multilayer spherules composed of phospholipid bilayers.
본 개시에 따른 인지질이중층으로 이루어진 다층소구체를 제조하는 단계는 70-90℃에서 에멀젼베이스에 70-90℃로 가온한 오일을 투입하면서 호머믹서 회전속도 3000-4000rpm 조건 및 패들믹서 회전속도 40-60rpm 조건에서 8-12분 동안 진행된다.The step of preparing multilayer spherules composed of phospholipid bilayers according to the present disclosure is to add oil heated to 70-90 ° C. to the emulsion base at 70-90 ° C. under conditions of a rotation speed of a Homer mixer of 3000-4000 rpm and a rotation speed of a paddle mixer of 40-90 ° C. It proceeds for 8-12 minutes at 60 rpm condition.
본 개시에 따른 인지질이중층으로 이루어진 다층소구체를 제조하는 단계는 투입되는 오일의 용해도는 이전의 수소첨가 분산액을 제조하는 단계에서 에탄올 5-10 중량부에 수소첨가 레시틴 10-30 중량부를 용해하였기 때문에, 가장 최적의 오일 용해도를 가진다.In the step of preparing multilayer globules composed of phospholipid bilayers according to the present disclosure, the solubility of the input oil is because 10-30 parts by weight of hydrogenated lecithin was dissolved in 5-10 parts by weight of ethanol in the previous step of preparing a hydrogenated dispersion. , has the most optimal oil solubility.
5 미만 중량부의 에탄올을 이용하는 경우에 다층소구체의 입자 크기가 매우 작고, 오일의 용해도가 감소하는 문제를 가지고, 10 초과 중량부의 에탄올을 이용하는 경우에는 10 미만 중량부의 에탄올을 이용하는 경우와 비교해서 입자 크기 및 오일의 용해도가 에탄올 중량부에 비례해서 증가하지 않고 제한적이기 때문에 에탄올 5-10 중량부를 이용함으로써 다층소구체의 입자를 안정한 상태로 유지하고 최적의 오일 용해도를 제공한다.In the case of using less than 5 parts by weight of ethanol, the particle size of the multilayered spherules is very small and the solubility of oil is reduced. Since the size and solubility of oil do not increase in proportion to parts by weight of ethanol and are limited, using 5-10 parts by weight of ethanol maintains the particles of the multilayer spherule in a stable state and provides optimum oil solubility.
본 개시에 따른 인지질이중층으로 이루어진 다층소구체는 수용성물질에 의해 길게 연장되고 다층의 구조를 가지는 판상미셀이 오일을 감싸면서 구상의 소구체로 닫혀지게 되고, 양말단이 연결되어 구형 모양의 다층구조를 가지는 전달체가 형성된다. 이때 복수의 인지질이중층(인지질막 Ⅰ, Ⅱ, Ⅲ)이 각각 구상의 소구체로 닫혀지게 되고, 경우에 따라서는 오일에는 유용성피부활성물질이 첨가된다.According to the present disclosure, multilayer spherules composed of phospholipid bilayers are elongated by water-soluble substances, and plate-like micelles having a multilayered structure are closed into spherical spherules while enveloping oil, and both ends are connected to form a spherical multilayered structure. branched carriers are formed. At this time, a plurality of phospholipid bilayers (phospholipid membranes I, II, and III) are closed into spherical spherules, respectively, and in some cases, oil-soluble skin-active substances are added to the oil.
본 개시에 따른 다층구조를 가지는 피부활성물질 전달체는 구형의 층상 미셀 구조를 형성한다.The skin active substance delivery system having a multi-layered structure according to the present disclosure forms a spherical layered micelle structure.
본 개시에 따른 수용성피부활성물질이 인지질이중층 사이에 위치하면, 유용성피부활성물질은 인지질이중층 내에 위치하고, 수용성피부활성물질이 인지질이중층 내에 위치하면, 유용성피부활성물질은 인지질이중층 사이에 위치하게 되며, 화장품의 제조과정에서 필요한 난용성피부활성물질은 인지질이중층 사이의 수용상부분에 위치한다. 난용성피부활성 물질은 올레아놀릭산(Oleanolic Acid), 우르솔릭산(Ursolic Acid), 세라마이드(Ceramide), 타자로틴(Tazarotene), 아다팔렌(Adapalene), 쿠마릭산(Coumaric Acid) 또는 퀘세틴(Quercetin)으로 이루어진 군 중에서 선택되는 적어도 어느 하나인 것이 바람직하다.When the water-soluble skin active material according to the present disclosure is located between the phospholipid bilayers, the oil-soluble skin active material is located within the phospholipid bilayer, and when the water-soluble skin active material is located within the phospholipid bilayer, the oil-soluble skin active material is located between the phospholipid bilayers, The poorly soluble skin active substances required in the manufacturing process of cosmetics are located in the aqueous phase between the phospholipid bilayers. Poorly soluble skin active substances include oleanolic acid, ursolic acid, ceramide, tazarotene, adapalene, coumaric acid or quercetin. It is preferably at least one selected from the group consisting of.
이와 같이 피부활성물질이 다층구조의 각층마다 분리하여 안정적으로 존재함으로써, 피부의 진피층까지 전달체의 파손없이 영양분 등의 피부활성물질을 안정적으로 전달된다.In this way, skin active substances such as nutrients are stably delivered to the dermal layer of the skin without damage to the delivery system, since the skin active substances are separated and stably present in each layer of the multilayer structure.
보다 구체적으로, 이하, 본 발명의 실시예를 통하여 더욱 상세히 설명한다. 그러나 이들 실시예는 본 발명을 예시하기 위한 것이며, 본 발명이 이들 실시예에 의해 한정되는 것은 아니다.More specifically, it will be described in more detail below through examples of the present invention. However, these examples are for illustrating the present invention, and the present invention is not limited by these examples.
실시예 1Example 1
본 개시에 따른 다층구조를 가지는 피부활성물질 전달체를 제조하기 위하여 수소첨가 레시틴 20 중량부를 에탄올 5중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하고, 80℃에서 탄소수 12-22의 포화지방알콜 20 중량부를 수소첨가 레시틴 분산액에 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 프리에멀젼베이스를 제조하고, 80℃에서 정제수 55 중량부에 프리에멀젼베이스 20 중량부와 수용성물질(히알루론산) 20 중량부를 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 에멀젼베이스를 제조하고, 80℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공하고, 80℃에서 에멀젼베이스 50 중량부에 오일(캐모마일 오일) 10 중량부를 투입하면서 호머믹서 회전속도 3500rpm 조건 및 패들믹서 회전속도 50rpm 조건에서 10분 동안 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조해서 다층구조를 가지는 피부활성물질 전달체를 완성하여 제품화하였다.In order to prepare a skin active substance delivery system having a multilayered structure according to the present disclosure, 20 parts by weight of hydrogenated lecithin was dissolved in 5 parts by weight of ethanol, and then hydrogenated lecithin dissolved in ethanol was added to 55 parts by weight of purified water at 60 ° C while adding AGI. A hydrogenated lecithin dispersion was prepared by stirring and dispersing for 10 minutes at a MIXER (general mixer) rotation speed of 900 rpm, and 20 parts by weight of a saturated fatty alcohol having 12-22 carbon atoms was added to the hydrogenated lecithin dispersion at 80 ° C while AGI MIXER ( General mixing mixer) Prepare a pre-emulsion base by stirring and dispersing for 10 minutes at a rotational speed of 900 rpm, and adding 20 parts by weight of the pre-emulsion base and 20 parts by weight of a water-soluble material (hyaluronic acid) to 55 parts by weight of purified water at 80 ° C while adding AGI MIXER (general mixer) stirring and dispersing for 10 minutes at a rotation speed of 900 rpm to prepare an emulsion base, uniformly filtering the emulsion base to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 80 ° C, electrode arrangement method The emulsion base, which has been filtered through, is placed between the upper and lower electrodes to provide a monopole charge, and 10 parts by weight of oil (chamomile oil) is added to 50 parts by weight of the emulsion base at 80 ° C. Homer mixer rotation speed 3500 rpm conditions and paddle mixer By stirring and dispersing for 10 minutes at a rotational speed of 50 rpm, multilayer spherules composed of phospholipid bilayers were prepared, and a skin active substance delivery system having a multilayer structure was completed and commercialized.
비교예 1Comparative Example 1
시중에 판매되고 있는 보습 및 피부진정 기능을 가진 화장품을 사용하였다.Commercially available cosmetics with moisturizing and skin soothing functions were used.
비교예 2Comparative Example 2
상기 실시예 1에서, 수소첨가 레시틴 20 중량부를 에탄올 5중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 대신, 수소첨가 레시틴 20 중량부를 에탄올 1 중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 것을 제외하고는 실시예 1과 동일한 방법으로 제조하였다.In Example 1, after dissolving 20 parts by weight of hydrogenated lecithin in 5 parts by weight of ethanol, adding hydrogenated lecithin dissolved in 55 parts by weight of purified water in ethanol at 60 ° C., AGI MIXER (general mixing mixer) rotation speed condition of 900 rpm Instead of preparing a hydrogenated lecithin dispersion by stirring and dispersing for 10 minutes, 20 parts by weight of hydrogenated lecithin is dissolved in 1 part by weight of ethanol, and then hydrogenated lecithin dissolved in ethanol is added to 55 parts by weight of purified water at 60 ° C. It was prepared in the same manner as in Example 1, except that the hydrogenated lecithin dispersion was prepared by stirring and dispersing for 10 minutes under the condition of an AGI MIXER (general mixing mixer) rotation speed of 900 rpm.
비교예 3Comparative Example 3
상기 실시예 1에서, 수소첨가 레시틴 20 중량부를 에탄올 5중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 대신, 수소첨가 레시틴 20 중량부를 에탄올 15 중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 것을 제외하고는 실시예 1과 동일한 방법으로 제조하였다.In Example 1, after dissolving 20 parts by weight of hydrogenated lecithin in 5 parts by weight of ethanol, adding hydrogenated lecithin dissolved in 55 parts by weight of purified water in ethanol at 60 ° C., AGI MIXER (general mixing mixer) rotation speed condition of 900 rpm Instead of preparing a hydrogenated lecithin dispersion by stirring and dispersing for 10 minutes, 20 parts by weight of hydrogenated lecithin is dissolved in 15 parts by weight of ethanol, and then hydrogenated lecithin dissolved in ethanol is added to 55 parts by weight of purified water at 60 ° C. It was prepared in the same manner as in Example 1, except that the hydrogenated lecithin dispersion was prepared by stirring and dispersing for 10 minutes under the condition of an AGI MIXER (general mixing mixer) rotation speed of 900 rpm.
비교예 4Comparative Example 4
상기 실시예 1에서, 70-90℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공하는 대신, 80℃에서 에멀젼베이스를 필터링하지 않고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공해서 에멀젼베이스를 후처리하는 것을 제외하고는 실시예 1과 동일한 방법으로 제조하였다.In Example 1, the emulsion base was uniformly filtered to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 70-90 ° C, and the filtered emulsion base was placed between the upper / lower electrodes through the electrode arrangement method Instead of providing unipolar charge, the emulsion base is not filtered at 80 ° C, and the emulsion base, which has been filtered through the electrode arrangement method, is placed between the upper / lower electrodes and unipolar charge is provided to post-process the emulsion base. It was prepared in the same way as in Example 1.
비교예 5Comparative Example 5
상기 실시예 1에서, 70-90℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공하는 대신, 80℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링만 진행해서 에멀젼베이스를 후처리하는 것을 제외하고는 실시예 1과 동일한 방법으로 제조하였다.In Example 1, the emulsion base was uniformly filtered to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 70-90 ° C, and the filtered emulsion base was placed between the upper / lower electrodes through the electrode arrangement method Instead of providing a monopole charge, the emulsion base was uniformly filtered to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 80 ° C., except that the emulsion base was post-treated. Prepared in the same manner as in Example 1 did
비교예 6Comparative Example 6
상기 실시예 1에서, 70-90℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공해서 인지질이중층으로 이루어진 다층소구체를 제조하는 대신, 80℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 초과로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공해서 인지질이중층으로 이루어진 다층소구체를 제조하는 것을 제외하고는 실시예 1과 동일한 방법으로 제조하였다.In Example 1, the emulsion base was uniformly filtered to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 70-90 ° C, and the filtered emulsion base was placed between the upper / lower electrodes through the electrode arrangement method Instead of producing multilayer spherules composed of phospholipid bilayers by providing a monopolar charge, the emulsion base is uniformly filtered to an average particle of greater than 90 nm through a 90 nm filter micron filter paper at 80 ° C, and the emulsion base filtered through an electrode arrangement method It was prepared in the same manner as in Example 1, except that multilayer spherules made of phospholipid bilayers were prepared by placing unipolar charges between the top/bottom electrodes.
비교예 7Comparative Example 7
상기 실시예 1에서, 70-90℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공해서 인지질이중층으로 이루어진 다층소구체를 제조하는 대신, 에멀젼베이스를 후처리하지 않고, 인지질이중층으로 이루어진 다층소구체를 제조하는 것을 제외하고는 실시예 1과 동일한 방법으로 제조하였다.In Example 1, the emulsion base was uniformly filtered to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 70-90 ° C, and the filtered emulsion base was placed between the upper / lower electrodes through the electrode arrangement method It was prepared in the same manner as in Example 1, except that multilayer spherules composed of phospholipid bilayers were prepared without post-treatment of the emulsion base instead of providing monopolar charge to prepare multilayer spherules composed of phospholipid bilayers.
<실험예 1: 피부 속 보습 측정 검사><Experimental Example 1: Moisture measurement test in the skin>
실시예 1 및 비교예 1 내지 비교예 7에 대해 피부활성물질의 전달 정도를검사하기 위해 12명의 패널을 선정하여 1주일 동안 매일 1회씩 피부에 같은 양의 피부활성물질을 포함한 샘플을 도포하여 피부 속 보습 효과를 측정하였다.For Example 1 and Comparative Examples 1 to 7, 12 panelists were selected to examine the degree of delivery of skin active substances, and a sample containing the same amount of skin active substances was applied to the skin once a day for 1 week. Inner moisturizing effect was measured.
피부 속보습 측정은 MoistureMeter D Compact(Delfin Technologies Ltd,Finland)를 이용하여 사용 전후에 동일한 조건과 방법으로 안면 볼 부위를 측정한다. 평가 값은 레이저를 이용하여 측정되며, 단위는 %(0~100), 국소 조직이 함유하고 있는 수분량을 측정한다. 피부 속 수분과 측정값은 비례한다.Moisturizing inside the skin is measured using the MoistureMeter D Compact (Delfin Technologies Ltd, Finland) on the cheeks of the face under the same conditions and method before and after use. The evaluation value is measured using a laser, and the unit is % (0 to 100), and the amount of moisture contained in the local tissue is measured. The moisture in the skin and the measured value are proportional.
이에 따라, 샘플을 사용 하기 전과 1주일 사용 후의 수분 측정값을 비교하였다. 이의 결과는 하기 [표 1]에 나타냈다.Accordingly, the moisture measurement values before and after using the sample for one week were compared. The results are shown in [Table 1] below.
상기 [표 1]의 결과로 보아, 실시예 1의 다층구조를 가지는 피부활성물질 전달체가 비교예 1 내지 비교예 7의 제품보다 피부활성물질 전달 성능이 우수함을 알 수 있다. 더욱 구체적으로, 실시예 1의 경우, 수소첨가 레시틴 20 중량부를 에탄올 5 중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하고, 80℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공해서 에멀젼베이스를 후처리함으로써 비교예 1 및 비교예 7보다 피부활성물질 전달 효과가 향상되는 것을 확인할 수 있었다. 수소첨가 레시틴 분산액에 에탄올 5 중량부를 사용하였을 때, 피부활성물질 전달체가 수소첨가 레시틴의 계면장력을 낮추어 장시간 안정성을 확보하는 유화안정 효과를 더욱 향상시키고, 오일(캐모마일 오일) 10 중량부의 용해도를 향상시켜 오일의 분산 안정성이 증가하여 균일하게 배열됨에 따라 피부활성물질을 전달하는데 효과적임을 확인할 수 있었다.From the results in [Table 1], it can be seen that the skin active substance delivery system having a multi-layered structure of Example 1 has superior skin active substance delivery performance than the products of Comparative Examples 1 to 7. More specifically, in the case of Example 1, after dissolving 20 parts by weight of hydrogenated lecithin in 5 parts by weight of ethanol, adding hydrogenated lecithin dissolved in ethanol to 55 parts by weight of purified water at 60 ° C. AGI MIXER (general mixing mixer) A hydrogenated lecithin dispersion was prepared by stirring and dispersing for 10 minutes at a rotational speed of 900 rpm, uniformly filtering the emulsion base to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 80 ° C, and filtering through an electrode array method. It was confirmed that the skin active substance delivery effect was improved compared to Comparative Examples 1 and 7 by post-processing the emulsion base by placing the completed emulsion base between the upper and lower electrodes and providing a monopole charge. When 5 parts by weight of ethanol is used in the hydrogenated lecithin dispersion, the skin active material carrier lowers the interfacial tension of the hydrogenated lecithin to further improve the emulsion stabilization effect that secures long-term stability, and improves the solubility of 10 parts by weight of oil (chamomile oil). As the dispersion stability of the oil increased and uniformly arranged, it was confirmed that it was effective in delivering skin active substances.
<실험예 2: 피부 안정성 검사><Experimental Example 2: Skin stability test>
실시예 1 및 비교예 1 내지 비교예 7에 대해 피부 질환이 없는 성인 남녀 12명을 대상으로 하여 자극 정도를 다음과 같이 평가하였다. 피험자들의 팔 전완부위를 SLS 1% 용액을 적용하여 의도적으로 피부장벽 손상을 일으켜 피부를 예민하게 만든 후, 20 μL의 시료를 도포한 하고 시험 부위를 밀폐한 후 24시간 동안 첩포하고, 첩포를 제거한 후 30분과 24시간 후에 피부에서의 반응을 CTFA 가이드라인에 제시된 terminology에 의거하여 검사한다. 판정기준은 다음과 같다. 판정기준에 의해 얻어진 시험자들의 점수를 평균하여 1 미만이면 저자극, 3 미만이면 경자극, 5 미만이면 중자극, 5 이상이면 강자극으로 평가한다.For Example 1 and Comparative Examples 1 to 7, 12 adult men and women without skin diseases were evaluated for irritation as follows. After applying SLS 1% solution to the forearm of the subjects to intentionally damage the skin barrier and make the skin sensitive, 20 μL of the sample was applied, the test site was sealed, the patch was applied for 24 hours, and the patch was removed. After 30 minutes and 24 hours, the skin reaction is examined according to the terminology presented in the CTFA guidelines. The judging criteria are as follows. The average of testers' scores obtained by the criterion is evaluated as mild irritation if less than 1, mild irritation if less than 3, medium irritation if less than 5, and strong irritation if less than 5.
상기 [표 2]의 결과로 보아, 실시예 1의 다층구조를 가지는 피부활성물질 전달체가 비교예 1 내지 비교예 7의 제품보다 높은 피부 안정성을 제공함을 알 수 있다.더욱 구체적으로, 실시예 1의 경우, 수소첨가 레시틴 20 중량부를 에탄올 5중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하였을 때, 피부활성물질 전달체의 유화안정성이 증가해서 피부 자극을 완화하는데 효과적임을 확인할 수 있었다.From the results in [Table 2], it can be seen that the skin active substance carrier having a multilayer structure of Example 1 provides higher skin stability than the products of Comparative Examples 1 to 7. More specifically, Example 1 In the case of, after dissolving 20 parts by weight of hydrogenated lecithin in 5 parts by weight of ethanol, adding hydrogenated lecithin dissolved in ethanol to 55 parts by weight of purified water at 60 ° C. for 10 minutes at an AGI MIXER (general mixer) rotational speed of 900 rpm. When the hydrogenated lecithin dispersion was prepared by stirring and dispersing while stirring, it was confirmed that the emulsification stability of the skin active material carrier was increased and effective in relieving skin irritation.
<실험예 3: 관능 검사><Experimental Example 3: sensory test>
실시예 1 및 비교예 1 내지 비교예 7에 대한 제품의 선호도를 확인하기 위해 전문적으로 실험실적 관능평가에 관여하는 종사자 20명에게 5점 척도법을 이용하여 평가하도록 하고, 각각의 결과에 대해 평균값으로 정리하였다. In order to confirm product preferences for Example 1 and Comparative Examples 1 to 7, 20 workers professionally involved in laboratory sensory evaluation were evaluated using a 5-point scale method, and the average value for each result Organized.
평가결과 각 제품에 대한 사용감, 사용 후 보습성, 세정감 등에 대하여 관능을 평가하여 5(매우 우수), 4(우수), 3(보통), 2(나쁨), 1(매우 나쁨)으로 평가하였다. 그 결과를 하기 [표 3]에 나타내었다.As a result of the evaluation, sensory evaluation was performed on the feeling of use, moisturizing after use, and cleansing feeling for each product, and it was evaluated as 5 (very good), 4 (excellent), 3 (average), 2 (poor), and 1 (very bad). . The results are shown in [Table 3] below.
상기 [표 3]의 결과로 보아, 실시예 1의 다층구조를 가지는 피부활성물질 전달체가 비교예 1 내지 비교예 7의 제품보다 높은 선호도를 제공함을 알 수 있다. 더욱 구체적으로, 실시예 1의 경우, 수소첨가 레시틴 20 중량부를 에탄올 5중량부에 용해시킨 후, 60℃에서 정제수 55 중량부에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 AGI MIXER(일반 혼합 믹서) 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하였을 때, 오일(캐모마일 오일) 10 중량부의 용해도가 증가하게 되어 피부활성물질 전달체가 수소첨가 레시틴의 계면장력을 낮추어 장시간 안정성을 확보하는 유화안정 효과를 더욱 향상시키고, 80℃에서 에멀젼베이스를 90㎚ 필터 마이크론 여과지를 통해 평균입자 90㎚ 이하로 균일하게 필터링하고, 전극 배열법을 통해 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공해서 에멀젼베이스를 후처리하는 공정으로 에멀젼베이스의 판상 구조를 더욱 균일하고 길게 연장하게 되어 더욱 큰 구형의 층상 구조를 제공함에 따라 많은 물질을 전달하기 때문에 관능검사에서 사용감, 보습성 및 세정감에서 높은 선호도를 확인할 수 있었다.From the results in [Table 3], it can be seen that the skin active substance delivery system having a multi-layered structure of Example 1 provides a higher preference than the products of Comparative Examples 1 to 7. More specifically, in the case of Example 1, after dissolving 20 parts by weight of hydrogenated lecithin in 5 parts by weight of ethanol, adding hydrogenated lecithin dissolved in ethanol to 55 parts by weight of purified water at 60 ° C. AGI MIXER (general mixing mixer) When a hydrogenated lecithin dispersion was prepared by stirring and dispersing at a rotational speed of 900 rpm for 10 minutes, the solubility of 10 parts by weight of oil (chamomile oil) increased, so that the skin active substance carrier lowered the interfacial tension of hydrogenated lecithin, resulting in long-term stability. The emulsion base is uniformly filtered to an average particle of 90 nm or less through a 90 nm filter micron filter paper at 80 ° C, and the emulsion base that has been filtered through the electrode arrangement method is placed between the top / bottom electrodes It is a process of post-processing the emulsion base by providing a monopole charge on the surface of the emulsion base, which elongates the plate-like structure of the emulsion base more uniformly and lengthens to provide a larger spherical layered structure, thereby delivering a lot of substances, so it is easy to use and moisturize in sensory tests. A high preference was confirmed in the comfort and cleaning feeling.
본 개시의 일 실시예에 따른 다층구조를 가지는 피부활성물질 전달체 제조방법은 종래 피부활성물질 전달체 제조방법과 비교할 때 구형의 안정한 리포좀 구조가 유연하게 피부의 좁은 틈을 통과하는 것이 가능하여 피부의 진피층까지 전달체의 파손없이 영양분 등의 활성물질을 안정적으로 전달하고, 피부의 여러 조직을 용이하게 통과하면서 피부의 각층에 유용성 피부활성물질, 수용성 피부활성물질 또는 난용성 피부활성물질을 각각 전달하고, 용해 포화도가 향상된 균일한 크기의 오일 입자를 제공해서 분산안정성이 높은 다층구조를 가지는 피부활성물질 전달체를 제공할 수 있다.The method for manufacturing a skin active substance delivery system having a multi-layered structure according to an embodiment of the present disclosure enables a spherical stable liposome structure to pass through a narrow gap in the skin flexibly compared to a conventional method for manufacturing a skin active substance delivery system, thereby allowing the dermal layer of the skin to pass through. It stably delivers active substances such as nutrients without damaging the delivery system, and delivers oil-soluble skin active substances, water-soluble skin active substances, or poorly soluble skin active substances to the stratum corneum of the skin while easily passing through various tissues of the skin, respectively, and dissolves It is possible to provide a skin active substance delivery system having a multi-layered structure with high dispersion stability by providing oil particles of uniform size with improved saturation.
본 개시의 앞선 설명은 당업자들이 본 개시를 행하거나 이용하는 것을 가능하게 하기 위해 제공된다. 본 개시의 다양한 수정예들이 당업자들에게 쉽게 자명할 것이고, 본원에 정의된 일반적인 원리들은 본 개시의 취지 또는 범위를 벗어나지 않으면서 다양한 변형예들에 적용될 수도 있다. 따라서, 본 개시는 본원에 설명된 예들에 제한되도록 의도된 것이 아니고, 본원에 개시된 원리들 및 신규한 특징들과 일관되는 최광의의 범위가 부여되도록 의도된다.The previous description of the present disclosure is provided to enable any person skilled in the art to make or use the present disclosure. Various modifications of the present disclosure will be readily apparent to those skilled in the art, and the general principles defined herein may be applied in various modifications without departing from the spirit or scope of the present disclosure. Thus, the present disclosure is not intended to be limited to the examples set forth herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
본 명세서에서는 본 개시가 일부 실시예들과 관련하여 설명되었지만, 본 개시가 속하는 기술분야의 통상의 기술자가 이해할 수 있는 본 개시의 범위를 벗어나지 않는 범위에서 다양한 변형 및 변경이 이루어질 수 있다는 점을 알아야 할 것이다. 또한, 그러한 변형 및 변경은 본 명세서에 첨부된 특허청구의 범위 내에 속하는 것으로 생각되어야 한다.Although the present disclosure has been described in relation to some embodiments in this specification, it should be noted that various modifications and changes may be made without departing from the scope of the present disclosure that can be understood by those skilled in the art to which the present disclosure pertains. something to do. Moreover, such modifications and variations are intended to fall within the scope of the claims appended hereto.
Claims (1)
80℃에서 탄소수 12-22의 포화지방알콜 20 중량부를 상기 수소첨가 레시틴 분산액에 투입하면서 교반하여 분산시켜 프리에멀젼베이스를 제조하는 단계;
80℃에서 정제수 55 중량부에 상기 프리에멀젼베이스와 수용성물질을 투입하면서 교반하여 분산시켜 에멀젼베이스를 제조하는 단계;
80℃에서 상기 에멀젼베이스를 필터 마이크론 여과지를 통해 상기 에멀젼베이스의 평균입자를 90㎚ 이하로 필터링하고, 필터링이 완료된 에멀젼베이스를 상면/하면 전극의 사이에 놓고 단극전하를 제공하여 판상 구조로 형성하는 단계; 및
80℃에서 상기 에멀젼베이스 50 중량부에 캐모마일 오일 10 중량부를 투입하면서 교반하여 분산시켜 인지질이중층으로 이루어진 다층소구체를 제조하는 단계
를 포함하고,
상기 수소첨가 레시틴 분산액을 제조하는 단계는, 정제수에 에탄올에 용해된 수소첨가 레시틴을 투입하면서 회전속도 900rpm 조건에서 10분 동안 교반하여 분산시켜 수소첨가 레시틴 분산액을 제조하는 것인,
다층구조를 가지는 피부활성물질 전달체 제조방법.In the step of preparing a hydrogenated lecithin dispersion, 20 parts by weight of the hydrogenated lecithin is dissolved in 5 parts by weight of ethanol, and then hydrogenated lecithin dissolved in 55 parts by weight of purified water is added to ethanol at 60 ° C. while stirring and dispersing to obtain a hydrogenated lecithin dispersion. manufacturing;
preparing a pre-emulsion base by adding 20 parts by weight of a saturated fatty alcohol having 12 to 22 carbon atoms to the hydrogenated lecithin dispersion at 80° C. while stirring and dispersing;
preparing an emulsion base by adding the pre-emulsion base and a water-soluble material to 55 parts by weight of purified water at 80° C. while stirring and dispersing;
At 80 ° C., filter the average particle of the emulsion base to 90 nm or less through filter micron filter paper for the emulsion base, and place the filtered emulsion base between the upper / lower electrodes to form a plate-like structure by providing a monopole charge step; and
Preparing multilayer spherules made of a phospholipid bilayer by stirring and dispersing while adding 10 parts by weight of chamomile oil to 50 parts by weight of the emulsion base at 80 ° C.
including,
The step of preparing the hydrogenated lecithin dispersion is to prepare a hydrogenated lecithin dispersion by adding hydrogenated lecithin dissolved in ethanol to purified water and stirring for 10 minutes at a rotational speed of 900 rpm to disperse it,
A method for manufacturing a skin active substance delivery system having a multi-layered structure.
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