KR100379067B1 - External formulation titrated extract of centella asiatica - Google Patents
External formulation titrated extract of centella asiatica Download PDFInfo
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- KR100379067B1 KR100379067B1 KR10-2000-0020745A KR20000020745A KR100379067B1 KR 100379067 B1 KR100379067 B1 KR 100379067B1 KR 20000020745 A KR20000020745 A KR 20000020745A KR 100379067 B1 KR100379067 B1 KR 100379067B1
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- South Korea
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- teca
- skin
- cream
- niosome
- centella asiatica
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- 239000000203 mixture Substances 0.000 title description 18
- 244000146462 Centella asiatica Species 0.000 title description 3
- 235000004032 Centella asiatica Nutrition 0.000 title description 3
- 238000009472 formulation Methods 0.000 title description 2
- 239000002353 niosome Substances 0.000 claims abstract description 11
- 239000000839 emulsion Substances 0.000 claims abstract description 8
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 claims abstract description 7
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 claims abstract description 7
- 229940106189 ceramide Drugs 0.000 claims abstract description 7
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 claims abstract description 7
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000002632 lipids Chemical class 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 229910052758 niobium Inorganic materials 0.000 claims abstract description 5
- 239000010955 niobium Substances 0.000 claims abstract description 5
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000004094 surface-active agent Substances 0.000 claims abstract description 5
- 229940059958 centella asiatica extract Drugs 0.000 claims abstract 2
- 239000006071 cream Substances 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 16
- 230000008961 swelling Effects 0.000 claims description 12
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- 239000003381 stabilizer Substances 0.000 claims description 4
- 229960001295 tocopherol Drugs 0.000 claims description 4
- 229930003799 tocopherol Natural products 0.000 claims description 4
- 235000010384 tocopherol Nutrition 0.000 claims description 4
- 239000011732 tocopherol Substances 0.000 claims description 4
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 4
- 235000012000 cholesterol Nutrition 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 7
- JXSVIVRDWWRQRT-UYDOISQJSA-N asiatic acid Chemical compound C1[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C JXSVIVRDWWRQRT-UYDOISQJSA-N 0.000 abstract description 6
- 229940011658 asiatic acid Drugs 0.000 abstract description 6
- LBGFKBYMNRAMFC-PYSQTNCISA-N asiatic acid Natural products C[C@@H]1CC[C@@]2(CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]5CC[C@@]34C)[C@]2(C)[C@H]1C)C(=O)O LBGFKBYMNRAMFC-PYSQTNCISA-N 0.000 abstract description 6
- CLXOLTFMHAXJST-UHFFFAOYSA-N esculentic acid Natural products C12CC=C3C4CC(C)(C(O)=O)CCC4(C(O)=O)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(CO)C CLXOLTFMHAXJST-UHFFFAOYSA-N 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- WYQVAPGDARQUBT-FGWHUCSPSA-N Madecassol Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)OC[C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)[C@]12CC[C@H]([C@@H]([C@H]1C=1[C@@]([C@@]3(CC[C@H]4[C@](C)(CO)[C@@H](O)[C@H](O)C[C@]4(C)[C@H]3CC=1)C)(C)CC2)C)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O WYQVAPGDARQUBT-FGWHUCSPSA-N 0.000 abstract description 2
- WYQVAPGDARQUBT-XCWYDTOWSA-N asiaticoside Natural products O=C(O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@H](O)[C@H](O)[C@H](O[C@H]3[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)[C@@H](CO)O2)O1)[C@@]12[C@@H]([C@@H](C)[C@H](C)CC1)C=1[C@](C)([C@@]3(C)[C@@H]([C@@]4(C)[C@H]([C@@](CO)(C)[C@@H](O)[C@H](O)C4)CC3)CC=1)CC2 WYQVAPGDARQUBT-XCWYDTOWSA-N 0.000 abstract description 2
- 229940022757 asiaticoside Drugs 0.000 abstract description 2
- QCYLIQBVLZBPNK-UHFFFAOYSA-N asiaticoside A Natural products O1C(C(=O)C(C)C)=CC(C)C(C2(C(OC(C)=O)CC34C5)C)C1CC2(C)C3CCC(C1(C)C)C45CCC1OC1OCC(O)C(O)C1O QCYLIQBVLZBPNK-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003921 oil Substances 0.000 abstract description 2
- 235000019198 oils Nutrition 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 abstract 1
- 239000008158 vegetable oil Substances 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 229940079593 drug Drugs 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 13
- 206010042674 Swelling Diseases 0.000 description 10
- 102000008186 Collagen Human genes 0.000 description 7
- 108010035532 Collagen Proteins 0.000 description 7
- 229920001436 collagen Polymers 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 230000002500 effect on skin Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 102000016942 Elastin Human genes 0.000 description 3
- 108010014258 Elastin Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 229920002549 elastin Polymers 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000037319 collagen production Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 241000208173 Apiaceae Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 241000275031 Nica Species 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000004347 all-trans-retinol derivatives Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000004299 exfoliation Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- PRAUVHZJPXOEIF-AOLYGAPISA-N madecassic acid Chemical compound C1[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]2[C@H](O)C[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C PRAUVHZJPXOEIF-AOLYGAPISA-N 0.000 description 1
- 229940011656 madecassic acid Drugs 0.000 description 1
- BUWCHLVSSFQLPN-UHFFFAOYSA-N madecassic acid Natural products CC1CCC2(CCC3(C)C(=CCC4C5(C)CC(O)C(O)C(C)(C5CCC34C)C(=O)O)C2C1C)C(=O)OC6OC(COC7OC(CO)C(OC8OC(C)C(O)C(O)C8O)C(O)C7O)C(O)C(O)C6O BUWCHLVSSFQLPN-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000036560 skin regeneration Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000013097 stability assessment Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
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- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65G—TRANSPORT OR STORAGE DEVICES, e.g. CONVEYORS FOR LOADING OR TIPPING, SHOP CONVEYOR SYSTEMS OR PNEUMATIC TUBE CONVEYORS
- B65G47/00—Article or material-handling devices associated with conveyors; Methods employing such devices
- B65G47/52—Devices for transferring articles or materials between conveyors i.e. discharging or feeding devices
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
- A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
- A23G3/50—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by shape, structure or physical form, e.g. products with supported structure
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
- A23P20/20—Making of laminated, multi-layered, stuffed or hollow foodstuffs, e.g. by wrapping in preformed edible dough sheets or in edible food containers
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2300/00—Processes
- A23V2300/31—Mechanical treatment
Landscapes
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Mechanical Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
병풀 정량 추출물 (아시아티코사이드가 약 40%, 마테카트산 약 30%, 아시아트산 약 30%로 구성되어 있으며, 이하, TECA라 한다)에 계면활성제 및 지질을 첨가하여 니오솜을 제조하고, 세라마이드에 식물유 및 라브라파크 등을 혼합하여 유상을 만든 후, 이 유상물에 니오솜을 혼합하여 신규한 니오솜-다중유제형 외용제를 제공하는 것이다. 니오솜-다중유제형 외용제는 팽창선조(튼살, stretching mark)의 예방과 치료에 탁월한 효과가 있다.Niobium was prepared by adding a surfactant and a lipid to the Centella asiatica extract (about 40% asiaticoside, about 30% asiatic acid, about 30% asiatic acid, hereinafter referred to as TECA), and preparing ceramide After mixing vegetable oil, Labra Park, etc. to make an oil phase, niosome is mixed with this oily substance to provide a novel niosome-multi-emulsion external preparation. Niosome-multi-emulsion external preparations have an excellent effect on the prevention and treatment of stretching marks.
Description
본 발명은 병풀 정량 추출물을 함유한 외용제에 관한 것으로, 보다 구체적으로는 이 추출물에 지질 및 계면활성제를 첨가하여 제조한 니오솜형을, 세라마이드를 함유한 유상에 혼합하여 제조한 니오솜 다중유제에 관한 것이다.The present invention relates to an external preparation containing a centrifugal extract of Centella asiatica, and more particularly to a niobium multi-emulsion agent prepared by mixing a niobium type prepared by adding lipid and surfactant to the extract, and mixing an oil phase containing ceramide. will be.
병풀(Centella asiatica)은 산형과(Umbelliferae)에 속한 식물로 병풀로부터 추출하여 얻은 물질을 병풀 정량 추출물(이하, "TECA"라 한다)로 물에 거이 녹지 않는다. TECA에는 여러 가지 물질이 존재하는데, 그의 주성분은 아시아티코사이드(asiaticicoside)가 약 40%, 마테카트산(madecassic acid)이 약 30%, 아시아트산(asiatic acid)이 약 30%로 구성되어 있으며, 이것은 상처 부위의 생육 및 재생을 촉진하는 용도로 사용되고 있다. Centella asiatica is a plant belonging to the family Umbelliferae and is a quantitative extract of the centellae (hereinafter referred to as "TECA"), which is hardly soluble in water. There are several substances in TECA, the main constituents of which are about 40% of asiaticicoside, about 30% of madecassic acid, and about 30% of asiatic acid. It is used for the purpose of promoting growth and regeneration of wound sites.
임산부와 성장기에 급격한 성장을 보인 청소년들에서 흔히 볼 수 있는 팽창선조(stretching mark)는 출산후 여성 및 한참 예민한 청소년들에게 미적인 자신감을 상실케 하거나 정신적인 스트레스를 유발하는 것이다.Stretching marks, commonly seen in pregnant women and adolescents with rapid growth, are associated with the loss of aesthetic confidence or mental stress in women and very sensitive adolescents after childbirth.
팽창선조는 발생 초기에는 치료 가능성이 높으나, 흰색으로 변해버린 다음에는 치료가 매우 어렵다. 현재까지는 팽창선조의 치료를 위하여 비타민A 유도체를 이용한 연고나 레이저를 이용한 색조변화를 유도하는 시술이 이용되거나, Erbium-YAG laser, ultrapulse CO2laser등을 이용하여 튼살 부위를 얇게 벗겨서 진피의 콜라겐 섬유세포를 자극하여 콜라겐 합성을 촉진시키는 방법이 주로 사용되고 있다.Swelling is more likely to be treated early in development, but is very difficult to treat after turning white. Thinning the stretch region until now for the treatment of expanded progenitor using the procedure of inducing the color change by using an ointment or a laser using a vitamin A derivative, or by using a Erbium-YAG laser, ultrapulse CO 2 laser stripped of the dermis collagen fiber The method of stimulating cells to promote collagen synthesis is mainly used.
팽창선조는 체내에 부신 피질 호르몬이 증가되어 진피층 내의 콜라겐 및 엘라스틴 섬유가 예민하게 반응하여 파괴되거나 또는 급격한 성장에 맞추어 콜라겐 생성속도가 따르지 못하거나 질적으로 불용성 콜라겐의 생성에 따른 피부의 수분이 감소로 각질이 박리되는 등의 원인에 의해 생기는 흔적이다.The swelling line is caused by the increased corticosteroids in the body, resulting in the sensitive reaction of collagen and elastin fibers in the dermal layer, or the rapid growth of collagen, which does not follow the rate of collagen production or decreases the moisture in the skin due to the production of insoluble collagen. It is a trace caused by the cause such as exfoliation of keratin.
TECA는 피부 재생력을 갖는 약물로 콜라겐 생성을 촉진시키는 것으로 알려져 있으나, 지금까지는 상처 치료 목적으로 사용되고 있을 뿐이다.TECA is known to promote collagen production as a drug with skin regeneration, but has been used for wound healing purposes so far.
본 발명자는 TECA 및 세라마이드를 함유한 니오솜/W/O 크림을 제조하여 팽창선조에 사용하여 팽창선조에 탁월한 효과가 있다는 사실을 알고 본 발명을 완성하게 되었다.The present inventors have completed the present invention by knowing that the niosome / W / O cream containing TECA and ceramide is used in the expansion line and has an excellent effect on the expansion line.
따라서 본 발명은 팽창선조의 예방 및 치료에 효과 있는 조성물을 제공하는 것이 첫째 목적이다.Therefore, it is a first object of the present invention to provide a composition that is effective in the prevention and treatment of swelling.
둘째 목적은 약물을 피부에 표적화시킬 수 있는 제제를 제공하는 것이다.The second object is to provide an agent capable of targeting the drug to the skin.
셋째 목적은 유효성분이 경시변화하지 않고 장시간 유지할 수 있는 안정제를 첨가하는 것이다.The third purpose is to add a stabilizer that can be maintained for a long time without changing the active ingredient over time.
도 1은 TECA를 함유한 니오솜의 사진1 is a photograph of niosomes containing TECA
도 2는 크림을 도포한 후, 60일 후 마우스 피부의 현미경 사진Figure 2 is a micrograph of the skin of the mouse 60 days after applying the cream
도 3는 진피층의 두께 그래프3 is a graph of the thickness of the dermal layer
도 4는 아시아코티사이드의 변화(25℃)4 is the change in asia cortiside (25 ℃)
도 5는 아시아코티사이드의 변화(40℃)5 is the change in asia cortiside (40 ℃)
도 6은 마테카트산의 변화(25℃)Fig. 6 shows changes in matecatenic acid (25 ° C)
도 7은 마테카트산의 변화(40℃)7 shows the change of matecatenic acid (40 ° C)
도 8은 아시아트산의 변화(25℃)8 is a change in asiatic acid (25 ℃)
도 9는 아시아트산의 변화(40℃)9 is a change in asiatic acid (40 ℃)
본 발명은 TECA에 계면활성제, 지질을 혼합하여 수중 니오솜을 제조한다.The present invention prepares niosomes in water by mixing a surfactant and a lipid with TECA.
이와 별도로 세라마이드를 함유한 유상 용액을 제조한 다음, 이 용액에 상기의 수중 니오솜을 첨가하여 TECA를 함유한 니오솜/W/O크림을 제조한다.Separately, an oily solution containing ceramide is prepared, and then niosom / W / O cream containing TECA is prepared by adding niosome in water to the solution.
이 때, TECA의 안정제로 토코페롤을 첨가할 수도 있다.At this time, tocopherol may be added as a stabilizer for TECA.
이하에서 본 발명을 더욱 상세히 설명하나, 본 발명이 이에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail, but the present invention is not limited thereto.
1. 니오솜(Niosome)의 제조1. Preparation of Niosome
(Baillie 등이 사용한 방법을 변형하여 제조하였다.)(Manufactured by modifying the method used by Bailey et al.)
스판60과 콜레스테롤을 몰비 1:1(2.155g:1.934g)과 2:1(2.872g:1.289g)로 정확히 칭량하고, TECA와 토코페롤을 2.7w/w%(1g)가 되도록 각각 칭량한 후, 250㎖ 플라스크에 넣고, 메탄올과 클로로포름 혼합액 20㎖에 용해시키고, 회전 증발 농축기에 장치하였다. 35∼45℃의 수욕 상에서 감압 증발 농축시켜 플라스크 내부에 얇은 막을 형성시키고, 높은 감압 펌프에 연결하여 1시간 더 건조시켜 용매를 완전히 제거한 다음, 증류수를 가하여 총중량이 37g이 되도록 하고, 50∼60℃에서 2시간 동안 초음파 처리하고, 호모게나이저로 9000rpm에서 10분간 교반하여 니오솜 현탁액을 제조하였다. 니오솜 현탁액을 100배 희석하여 슬라이드에 적하한 후, 건조하여 영상 판독기(image analyzer, Leika Q600)를 이용하여 관찰한 결과, 니오솜의 형성을 확인하였다. 도 1에 나타난 바와 같이 니오솜의 크기에 편차가 있음을 확인하였다.Span 60 and cholesterol were precisely weighed at a molar ratio of 1: 1 (2.155g: 1.934g) and 2: 1 (2.872g: 1.289g), and then weighed to 2.7w / w% (1g) of TECA and tocopherol, respectively. The mixture was placed in a 250 ml flask, dissolved in 20 ml of a mixture of methanol and chloroform, and placed in a rotary evaporator. Concentrate under reduced pressure on a water bath at 35 to 45 ° C to form a thin film inside the flask, dry for an additional 1 hour by connecting to a high pressure pump, remove the solvent completely, add distilled water to make the gross weight 37g, and 50 to 60 ° C. Sonication for 2 hours at, and stirred for 10 minutes at 9000 rpm with a homogenizer to prepare a niosomal suspension. After diluting the niosomal suspension 100 times and dropping it onto the slide, it was dried and observed with an image analyzer (Image analyzer, Leika Q600), and the formation of niosomal was confirmed. As shown in Figure 1 it was confirmed that there is a deviation in the size of the niosome.
2. TECA함유 니오솜/W/O 크림의 제조2. Preparation of TECA-containing Niosome / W / O Cream
표 1에 기재된 성분을 정확히 칭량하여 하기 제조방법으로 니오솜과 다중유제 크림을 제조한다.Accurately weigh the ingredients listed in Table 1 to prepare niosomes and multi-emulsion creams with the following preparation methods.
TECA 함유 니오솜 현탁액에 5%폴록사머 및 프로필렌글리콜을 첨가하고 9000rpm, 1분간 호모게나이저로 균질화하여 TECA함유 니오솜/W 현탁액을 제조한다. 따로 세라마이드, 백색 바셀린, 세틸알콜, 올리브유 및 라브라파크(Labrafac) 혼합물을 80℃에서 용융시키고, 9000rpm에서 1분간 균질화시켜 얻은 유상 용액에 TECA함유 니오솜 현탁액을 넣고 9000rpm, 30분간 균질화시키고, 교반하면서 실온으로 냉각하여 목적하는 크림(이하, TECA N/W/O 이라고 한다)을 제조하여다.5% poloxamer and propylene glycol are added to a TECA-containing nisomal suspension and homogenized with a homogenizer at 9000 rpm for 1 minute to prepare a TECA-containing nisomal / W suspension. Separately, a mixture of ceramide, white petrolatum, cetyl alcohol, olive oil, and Labrafac was melted at 80 ° C., and homogenized at 9000 rpm for 1 minute to add a nica suspension containing TECA, homogenized at 9000 rpm for 30 minutes, and stirred. While cooling to room temperature while producing the desired cream (hereinafter referred to as TECA N / W / O).
3. In vitro 피부 투과 시험3. In vitro skin penetration test
실험동물Laboratory animals
실험동물은 동물실에서 1주일간 적응시킨 후에 사용하였고, 동물 사육 조건은 온도 20∼23℃, 상대습도 55±5%, 명암 교대시간 12시간을 유지하였다. 실험 중을 제외하고는 먹이와 물을 충분히 공급하였다.The experimental animals were used after adapting for one week in the animal room, and the animal breeding conditions were maintained at a temperature of 20 to 23 ° C., a relative humidity of 55 ± 5%, and a contrast time of 12 hours. Except during the experiment, sufficient food and water were supplied.
가. 무모 마우스의 피부 적출end. Skin Extraction of Hairless Mouse
8주령의 웅성 무모 마우스의 피부를 적출하여 시험에 사용하였다. 무모 마우스를 경추 탈골법으로 안락사시켜 등과 복부쪽 피부를 떼어낸 다음, 피부 밑에 붙어 있는 피하지방을 생리식염수로 피부가 상하지 않도록 조심스럽게 제거하였다. 보관 과정없이 적출 즉시 실험에 사용하였다.Skin of 8 week old male hairless mice was extracted and used for the test. The hairless mouse was euthanized by cervical dislocation to remove the skin from the back and abdomen, and the subcutaneous fat under the skin was carefully removed so as not to damage the skin with saline solution. It was used for the experiment immediately after extraction without storage process.
나. 피부 투과 시험I. Skin penetration test
TECA N/W/O 크림으로부터 무모 마우스를 통한 약물의 피부 투과 속도를 프란츠 디퓨젼 셀(Franz diffusion cell)을 사용하여 측정하였다. 피부 투과 시험은 조성물 1 내지 조성물 5를 가지고 투과 시험을 실시하였다.The rate of skin penetration of the drug from the TECA N / W / O cream through the hairless mice was measured using a Franz diffusion cell. The skin permeation test was carried out with the compositions 1-5.
크림을 도포한 피부의 면적은 2.303 ㎠이고 receptor phase는 pH 7.4 등장 인산염 완충액으로 채워 부피를 11.8㎖로, 온도를 37±0.5℃로 유지하고, 자석 교반기를 이용하여 600rpm에서 일정하게 교반하였다.The area of the cream-coated skin was 2.303 cm 2 and the receptor phase was filled with pH 7.4 isotonic phosphate buffer to maintain a volume of 11.8 ml, a temperature of 37 ± 0.5 ° C., and constant stirring at 600 rpm using a magnetic stirrer.
각 조성물 0.5g을 피부 표면에 도포하고, 12시간까지 일정시간마다 0.2㎖의 receptor phase를 마이크로실린지로 채취하여 HPLC에 직접 주입하였다. 채취된 양은 즉시 동량의 pH 7.4등장 인산염 완충액으로 보충하였다.0.5 g of each composition was applied to the surface of the skin, and 0.2 ml of the receptor phase was collected with a microsyringe and injected directly into the HPLC every 12 hours. The collected amount was immediately supplemented with an equal amount of pH 7.4 isophosphate buffer.
다. 시험결과All. Test result
아시아티코사이드, 마테카트산 및 아시아트산은 투과되지 않았다.Asiaticoside, matecatenic acid and asiatic acid were not permeable.
4. 피부내 약물 침적 시험4. Intradermal drug deposition test
가. 검량선 작성end. Create calibration curve
TECA를 메탄올에 6.25, 12.5, 25, 50, 100 및 200㎍/㎖의 농도로 용해하여 HPLC로 측정하여 검량선을 작성하였다.TECA was dissolved in methanol at concentrations of 6.25, 12.5, 25, 50, 100 and 200 μg / ml and measured by HPLC to create a calibration curve.
나. 피부내 약물 침적I. Intradermal drug deposition
In vivo 실험으로, 8 주령의 웅성 무모 마우스의 사지를 결박하여 배를 위로 향하게 고정대에 고정하고 복부에 면적 2.303㎠의 원을 그려 조성물2 내지 조성물 5, 니오솜 현탁액 각 200mg을 원안에 고르게 바른 후, 6시간 후에 피부에 남은 약물을 메탄올로 완전히 씻은 다음 피부를 적출하였다. 적출된 피부는 해부용 가위를 사용하여 잘게 자른 뒤 메탄올을 10㎖ 가한 후, 5분간 보텍스(vortex)로 진탕하고, 하룻밤 방치하고, 30분간 초음파(sonication) 처리한 후, 조직 분쇄기(tissue grinder)를 이용하여 10분간 적출 피부를 분쇄하였다. 분쇄한 액을 15000rpm으로 원심분리 한 후, 상징액을 취하여 여과하고, 이를 검액으로 하여 HPLC에 직접 주입하였다.In an in vivo experiment, the limb of an 8-week-old male hairless mouse was fixed to the stator with the stomach upright, a circle with an area of 2.303 cm 2 was drawn on the abdomen, and 200 mg of composition 2 to composition 5 and niosomal suspension were evenly applied in a circle. After 6 hours, the drug remaining on the skin was thoroughly washed with methanol and the skin was extracted. The extracted skin is finely chopped using an anatomical scissors, 10 ml of methanol is added, shaken with a vortex for 5 minutes, left overnight, sonicated for 30 minutes, and then a tissue grinder. The extracted skin was ground for 10 minutes using. The pulverized solution was centrifuged at 15000 rpm, the supernatant was collected and filtered, and this was directly injected into HPLC as a sample solution.
또한, in vitro 실험으로, 적출피부에서 약물의 투과 실험을 12시간 동안 행하고, 이 실험에 사용한 피부를 in vivo 침적 실험과 같은 조작으로 처리하여 적출피부내의 약물을 정량하였다.Further, in vitro experiments, the drug permeation experiments were carried out in the extracted skin for 12 hours, and the skin used in this experiment was treated in the same manner as the in vivo deposition test to quantify the drug in the extracted skin.
다. 실험결과All. Experiment result
In vitro 실험으로 적출피부에서 12시간 동안의 약물 침적량을 측정한 결과를 표 2에 나타내었고, in vivo 실험으로 무모마우스의 북부쪽 피부에 6시간 동안 침적된 약물량을 측정한 결과를 표 3에 나타내었다.Table 2 shows the results of 12 hours of drug deposition in the extracted skin by in vitro experiments, and the results of 6 hours of drug deposition on the northern skin of hairless mice by in vivo experiments. Indicated.
(mean ± S.D, n=3) (mean ± SD, n = 3)
(mean ± S>D, n=3)(mean ± S> D, n = 3)
5. TECA N/W/O 크림의 피부 조직에 대한시험5. Testing of skin tissue of TECA N / W / O Cream
8주령의 웅성 무모 마우스를 실험동물로 하였다. 각 군은 5마리로 하고, 실험기간 동안 물과 먹이를 충분이 공급하였다.Male hairless mice of 8 weeks of age were used as experimental animals. Each group consisted of 5 rats, and water and food were sufficiently supplied during the experiment.
무모 마우스의 복부 전체에 조성물 4, 약물이 없는 대조 기재크림을 각각 200mg씩 8주 동안 하루에 한번 고루 발라주었다. 크림을 적용한 후, 복부 피부를 적출하여 뷰잉 액(Bouin's solution)에 담가 피부 고정을 하고, 적절한 크기로 잘라 파라핀으로 embedding을 한 다음, 5㎛정도로 수직 단면으로 잘라 슬라이드를 만든 후, 메이손 트리크롬(Masson's Trichrome) 염색법으로 염색하여 광학 현미경으로 관찰하였다. 크림을 발라 주지 않은 8주령의 어린 무모 마우스와 16주령의 대조군에 대해서도 같은 과정으로 처리하여 비교 실험하였다. 관찰한 결과는 도 2에 사진으로 나타내고, 각 진피층의 두께를 측정한 값을 표 4와 도 3에 나타내었다.The entire abdomen of hairless mice was spread evenly once a day for 8 weeks with 200 mg each of composition 4, a drug-free control base cream. After applying the cream, the abdominal skin was extracted, soaked in Boin's solution, the skin was fixed, cut into appropriate sizes, embedded with paraffin, and then cut into a vertical section of about 5 μm to make a slide, and then maison trichrome (Masson's Trichrome) staining method was observed under an optical microscope. The same procedure was also applied to the young hairless mice of 8 weeks old and the control group of 16 weeks old who did not apply the cream. The observed result is shown in the photograph in FIG. 2, and the value which measured the thickness of each dermal layer is shown in Table 4 and FIG.
(시험결과)(Test result)
무모 마우스의 성장에 따라 피부의 진피층은 콜라겐 및 엘라스틴 섬유의 생성으로 증가되는데, 제제를 발라주지 않은 16주령의 대조군은 8주령의 대조군에 비해 진피층 두께가 25.46㎛증가하였고, 약물이 없는 대조기제크림을 발라준 군의 진피조직은 약물을 바르지 않은 16주령의 대조군과 거의 같은 증가 양상을 보여서 기제 자체에는 콜라겐과 엘라스틴 섬유의 생성을 증가시키는 기능이 없음을 알 수 있었다(p>0.05). 본 발명의 조성물 4는 8주령 대조군보다 80.74㎛가 증가되었으며, 이는 16주령 대조군의 증가율에 비해 약 3.2배가 더 증가된 것으로 TECA N/W/O 크림이 진피층의 두께를 증가시키는 것을 확인하였다(p>0.01).As the hairless mouse grows, the dermal layer of the skin increases with the production of collagen and elastin fibres.The 16-week-old control group increased 25.46 μm in thickness compared to the 8-week-old control group, and the drug-free control cream The dermal tissue of the group treated with showed the same increase as that of the 16-week-old control group without the drug, indicating that the mechanism itself had no function of increasing the production of collagen and elastin fibers (p> 0.05). Composition 4 of the present invention was increased 80.74㎛ than the 8-week-old control, which is about 3.2 times more than the increase rate of the 16-week-old control was confirmed that the TECA N / W / O cream increases the thickness of the dermal layer (p > 0.01).
(mean ± S.D, n=4)(mean ± S.D, n = 4)
6. 가속 안정성 평가6. Acceleration Stability Assessment
가. 함량 시험end. Content test
TECA N/W/O 크림 0.1g을 취한 후, 메탄올을 가하여 10㎖로 하고, 실온에서 1시간 동안 초음파 처리하고, 보텍스 믹서(vortexing mixer)를 이용하여 1분간 격렬히 교반한 다음, 0.45㎛ 맴브레인 필러로 여과한 것을 검액으로 하여 약물의 함량을 HPLC로 측정하였다.Take 0.1 g of TECA N / W / O cream, add 10 ml of methanol, sonicate at room temperature for 1 hour, stir vigorously for 1 minute using a vortexing mixer, and then apply 0.45 μm membrane filler. The content of the drug was measured by HPLC using the filtrate as a sample solution.
나. 조성물의 가속안정성 시험I. Accelerated Stability Test of the Composition
각 처방 제제를 밀봉하여 25℃ 및 40℃의 항온조에서 90일간 보관하면서 30일마다 제제 0.1g을 취하여 메탄올을 가해 10㎖로 하고, 이를 검액으로 한 후, TECA의 약을 함량 시험의 조건과 동일하게 하여 측정하였다.Each prescription was sealed and stored in a thermostat at 25 ° C and 40 ° C for 90 days, taking 0.1g of the formulation every 30 days, adding 10 ml of methanol to make the sample solution, and then adjusting the drug of TECA to the same as the conditions of the content test. Measured by.
다. 시험결과All. Test result
본 발명의 조성물크림을 90일 동안 25℃와 40℃에서 보관하며 가속 안정성 시험을 실시한 결과, 물리적인 성상은 모두 변화가 없었고 각 조성물 중 약물의 안정성 결과는 표 5 와 도 4 내지 도 9와 같다The composition cream of the present invention was stored at 25 ° C. and 40 ° C. for 90 days and subjected to an accelerated stability test. As a result, the physical properties of the composition were not changed.
7. 팽창선조에 대한 인체 임상실험 7. Clinical trial of human body for swelling
가. 실험방법end. Experiment method
나이 20세∼30세(평균나이 24±1)의 여성을 대상으로 15명을 선정하여 팽창선조에 대한 치료효과를 팽창선조, 색도 및 팽창선조의 길이(cm), 넓이(mm)를 측정하여 평가하였다.15 women were selected from women aged 20 to 30 years (mean age 24 ± 1) to measure the effects of treatment on inflation ancestors by measuring inflation ancestry, chromaticity and length (cm) and width (mm) Evaluated.
나. 실험측정 기준I. Experimental Standard
본 조성물크림을 피부에 도포하기 전에 팽창선조의 넓이, 길이를 측정하고(D0) 27, 55, 83일에 각각 측정하여 변화되는 양상을 평가하였다. 피부의 팽창선조의 수, 색의 변화는 이미지 아나소프트웨어(image anasoftware)가 장착된 비디오마이크로스코프(videomicroscope)를 사용하여 측정하였다.Before applying the composition cream to the skin, the width and length of the swelling line was measured (D0) and measured at 27, 55, and 83 days, respectively, to evaluate the changing aspect. The number of swelling ancestors in the skin and the change in color were measured using a videomicroscope equipped with image anasoftware.
다. 실험결과All. Experiment result
위의 실험방법에 의한 결과를 표 6과 표 7에 표시하였다.The results of the above experimental method are shown in Table 6 and Table 7.
시험결론Conclusion
이상의 실험은 20세에서 30세의 여성(평균나이 24±1)을 대상으로 실험한 것으로서 시험실시중 TECA 외용제에 의한 알레르기 증세나 자극증세는 나타나지 않았으며, 1일 2회 피부에 도포하여 측정한 값은 팽창선조의 길이와 폭의 측정치는 길이가 시험전 값이 3.8±0.5에서 84일째 3.5±0.6으로 큰 변화는 없었으며, 폭은 시험전 4.1±0.5에서 84일째 3.3±0.6으로서 약간의 감소를 나타내었다.The above experiments were conducted in women aged 20 to 30 years (mean age 24 ± 1), and did not show any allergic or irritable symptoms caused by external application of TECA during the test. The measured value of the length and width of the swelling line was not significantly changed from the value of the pre-test to the value of 3.5 ± 0.6 on the 84th day from 3.8 ± 0.5, and the width decreased slightly to 3.3 ± 0.6 on the 84th day from 4.1 ± 0.5. Indicated.
또한, 팽창선조의 수, 색을 측정한 값은 실험전 수가 4.6±0.7이었으나, 84일째 측정한 값은 3.7±0.9로 감소하였고, 색은 시험전 3.6±0.9에서 84일째 측정한 값은 1.7±0.6으로 50%이상 감소하였다.In addition, the measured number and color of the swelling line was 4.6 ± 0.7 before the experiment, but the value measured on the 84th day decreased to 3.7 ± 0.9, and the color measured on the 84th day from 3.6 ± 0.9 before the test was 1.7 ±. It was reduced by more than 50% to 0.6.
기존의 TECA의 함유 외용제가 팽창선조를 치료하는데 6개월 정도 소요되는 것에 비하여 본 발명의 조성물은 84일로서 탁월한 효과가 있다.The composition of the present invention has excellent effect as 84 days, compared to the conventional external preparation containing TECA takes about 6 months to treat the swelling.
종래의 TECA 함유 연고에 비해 본 발명의 TECA 함유 니오솜 다중유제 크림은 피부를 통한 약물의 투과가 일어나지 않으며, 약물의 피부내에 침적량이 현저히 높은 수치를 나타내며, 임상실험결과 팽창선조에 현저한 효과가 있다. 열에 대하여 성분변화가 잘 생기나 안정제로 토코페롤을 첨가하므로 TECA의 성분이 안정하여 장기간 보관할 수 있다.Compared with the conventional TECA-containing ointment, the TECA-containing nisom multi-emulsion cream of the present invention does not cause the drug to penetrate through the skin, and shows a significantly high deposition amount of the drug in the skin, and has a remarkable effect on the swelling ancestry as a result of clinical trials. . The composition changes well against heat, but since tocopherol is added as a stabilizer, the components of TECA are stable and can be stored for a long time.
Claims (4)
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| KR100901340B1 (en) | 2007-08-31 | 2009-06-09 | (주)아모레퍼시픽 | Cosmetic composition for anti-stretch mark effect on the skin containing dipalmitoyl hydroxyproline |
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| KR100760366B1 (en) * | 2006-01-02 | 2007-10-04 | 주식회사 엘지생활건강 | Miniemulsion cosmetic composition containing prangenidin |
| ITUA20162223A1 (en) * | 2016-04-01 | 2017-10-01 | Linnea Sa | Topical composition including plant extracts |
| KR102002283B1 (en) | 2017-09-05 | 2019-07-23 | 코스맥스 주식회사 | Composition comprising eutectic mixture of extract of centella asiatica |
| KR102051417B1 (en) * | 2018-04-12 | 2019-12-03 | 주식회사 위노바 | The cosmetic composition for the prevention and improvement of striae distensae |
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| JPS6379809A (en) * | 1986-09-22 | 1988-04-09 | Shiseido Co Ltd | Skin drug for external use |
| KR960022435A (en) * | 1994-12-03 | 1996-07-18 | 강재헌 | Asiatic Acid Derivatives, Methods for Manufacturing the Same, and Wound Care Agents Containing the Same |
| WO1997039734A1 (en) * | 1996-04-23 | 1997-10-30 | The Procter & Gamble Company | Methods of regulating skin condition with centella asiatica extract |
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|---|---|---|---|---|
| JPS6379809A (en) * | 1986-09-22 | 1988-04-09 | Shiseido Co Ltd | Skin drug for external use |
| KR960022435A (en) * | 1994-12-03 | 1996-07-18 | 강재헌 | Asiatic Acid Derivatives, Methods for Manufacturing the Same, and Wound Care Agents Containing the Same |
| WO1997039734A1 (en) * | 1996-04-23 | 1997-10-30 | The Procter & Gamble Company | Methods of regulating skin condition with centella asiatica extract |
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| KR100901340B1 (en) | 2007-08-31 | 2009-06-09 | (주)아모레퍼시픽 | Cosmetic composition for anti-stretch mark effect on the skin containing dipalmitoyl hydroxyproline |
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