US20030175315A1 - Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same - Google Patents

Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same Download PDF

Info

Publication number
US20030175315A1
US20030175315A1 US10/336,024 US33602403A US2003175315A1 US 20030175315 A1 US20030175315 A1 US 20030175315A1 US 33602403 A US33602403 A US 33602403A US 2003175315 A1 US2003175315 A1 US 2003175315A1
Authority
US
United States
Prior art keywords
nanoemulsion
ginseng saponin
compound
skin
β
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/336,024
Inventor
Byung Yoo
Byung Kang
Myeong Yeom
Dae Sung
Sang Han
Han Kim
Hee Ju
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pacific Corp
Original Assignee
Pacific Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to KR20020000614A priority Critical patent/KR100465977B1/en
Priority to KR2002-614 priority
Priority to KR2002-613 priority
Priority to KR20020000613A priority patent/KR100465976B1/en
Priority to KR2002-19032 priority
Priority to KR20020019032A priority patent/KR100835863B1/en
Priority to KR1020020029179A priority patent/KR100835864B1/en
Priority to KR2002-29179 priority
Application filed by Pacific Corp filed Critical Pacific Corp
Assigned to PACIFIC CORPORATION reassignment PACIFIC CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HAN, SANG HOON, JU, HEE KYUNG, KANG, BYUNG YOUNG, KIM, HAN KON, SUNG, DAE SEOK, YEOM, MYEONG HOON, YOO, BYUNG HEE
Publication of US20030175315A1 publication Critical patent/US20030175315A1/en
Application status is Abandoned legal-status Critical

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/02Cosmetics or similar toilet preparations characterised by special physical form
    • A61K8/04Dispersions; Emulsions
    • A61K8/06Emulsions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/02Cosmetics or similar toilet preparations characterised by special physical form
    • A61K8/04Dispersions; Emulsions
    • A61K8/06Emulsions
    • A61K8/068Microemulsions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/96Cosmetics or similar toilet preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toilet preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILET PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/21Emulsions characterized by droplet sizes below 1 micron
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41Particular ingredients further characterized by their size
    • A61K2800/413Nanosized, i.e. having sizes below 100 nm

Abstract

Disclosed herein is nanoemulsion prepared by emulsifying main metabolites of ginseng saponin obtained by conversion of glucose, i.e. compound K (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol), ginsenoside F1 (20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol) and compound Y (20-O-[α-L-arabinopyranosyl(1→6)-β-D-glucopyranosyl]-20(S)-protopanaxadiol); and admixture thereof, in fine emulsion or liposome with dermotropic emulsifier by nano-emulsification; and having enhanced skin penetration, so to be effective in promoting proliferation of fibroblast and biosynthesis of collagen.

Description

    BACKGROUND OF THE INVENTION
  • 1. Field of the Invention [0001]
  • The present invention relates to nanoemulsion comprising metabolites of ginseng saponin as an effective component and to a method for preparing the same, and to a skin-care composition for anti-aging containing the same. More particularly, the present invention relates to nanoemulsion comprising main metabolites of ginseng saponin obtained by conversion of glucose in the saponin, i.e. 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, called “compound K” (hereinafter, “compound K”), 20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol, called “ginsenoside F1” (hereinafter, “ginsenoside F1”) and 20-O-[α-L-arabinopyranosyl(1→6)-β-D-glucopyranosyl]-20(S)-protopanaxadiol, called “compound Y” (hereinafter, “compound Y”), and admixture thereof. The present nanoemulsion may be prepared by emulsifying metabolites of ginseng saponin in fine emulsion or liposome with dermotropic emulsifier such as lecithin, by nano-emulsification such as high pressure homogenization and solvent extraction. The present nanoemulsion has enhanced skin penetration and thereby the cosmetic composition containing the same can promote proliferation of fibroblast and biosynthesis of collagen, so as to effectively prevent skin aging. [0002]
  • 2. Description of Prior Art [0003]
  • Generally, skin is the first protective barrier against the surrounding environments such as change of temperature or humidity, UV and contaminants, and plays an important role in maintaining homeostasis such as thermoregulation. However, the skin may be damaged by excessive physical or chemical irritations, stress or sub-alimentation, resulting in losing normal functions and elasticity or so, to cause keratinization and to form wrinkles. On this, in order to prevent skin aging and to maintain healthy and elastic skin, a lot of efforts have been made to develop cosmetics containing biologically active materials obtained from animals, plants or microorganisms that play a role in maintaining skin functions and in activating skin cells, resulting in effectively controlling skin aging. [0004]
  • However, these active materials have some drawbacks such as insufficient efficacy or side effects such as skin irritation. [0005]
  • Accordingly, much researches has been made in order to provide cosmetic materials for anti-aging without skin irritation. Specially, many concerns on the extracts of ginseng led to extensive studies. These studies have widely focused on ginseng extracts, i.e. ginseng saponins and the intestinal flora metabolites thereof, which are obtained by isolation and conversion of glucose (via acid or alkaline hydrolysis or enzyme reaction), for example, compound K, ginsenoside F1 and compound Y. [0006]
  • Ginseng saponin has a specific chemical structure in which sugar such as glucose, rhamnose, xylose or arabinose is linked via ether bond to R[0007] 1, R2 or R3 positioned-alcoholic OH of aglycon of triterpene, a family of dammarane. Up to date, in total 29 kinds of saponins have been identified. Shibata, in 1964, called each component of said ginseng saponin “ginsenoside”, which refers to glycoside contained in ginseng. Ginsenosides are classified into ginsenoside-Ro which is a family of oleanane saponin, and ginsenoside-Ra, -Rb1, -Rb2, -Rc, -Rd, -Re, -Rf, -Rg1, -Rg2, -Rg3 and -Rh according to the developing orders on TLC (thin-layer chromatography).
  • These ginseng saponins were found to be completely different from those found in about 750 other kinds of herbs in viewpoint of chemical structure and medical activity. Especially, ginseng saponins were revealed to have mild medicinal property and no toxicity or little hemolysis with excessive administration. [0008]
  • Further, it was reported that ginseng saponin applied on the skin in the form of liposome, which is a complex with phospholipid, has effects on imparting vitality to aged skin, increasing elasticity and hydration of the skin and accelerating blood circulation of the skin. (Curri. S B, Gezz, Z, Longhi, M G, Castelpietra, R: Fitoterapia, 57, 217(1986); Gezzi, A, Longhi, M G, Mazzoleni, R, Curri, S B: Fitoterapia, 57, 15(1986); Bombardelli, E. Curri, S B, Gariboldi, P L: Proc. 5th Intl. Ginseng Sym. Seoul Korea, 11(1988)) [0009]
  • Thereafter, in order to apply ginseng saponin as an anti-aging material, ginseng aglycon was bioconverted for enhancing skin penetration and tested for the efficacy on the skin, which was confirmed as the same as that of ginseng saponin. [0010]
  • As for the applications of ginseng extracts or saponins, U.S. Pat. Nos. 5,565,207, 5,567,419, 5,578,312, 5,663,160, 5,626,868, 5,753,242, 5,747,300, 5,853,705, 6,027,728, 6,063,366, 6,221,372 and 6,228,378 disclosed cosmetic compositions and U.S. Pat. Nos. 5,569,459, 5,571,516, 5,587,167, 5,674,488, 5,665,393, 5,629,316, 5,776,460, 5,739,165, 5,916,555, 6,071,521, 6,083,512 and 6,255,313 disclosed pharmaceutical compositions. In addition, U.S. Pat. Nos. 5,591,611, 5,591,612, 5,736,380, 5,789,392, 5,780,620, 5,922,580, 5,935,636, 6,132,726, 6,156,817 and 6,207,164 disclosed methods for isolation and purification of ginseng saponins. [0011]
  • However, ginseng saponin is extremely hydrophilic and has high molecular weight due to its chemical structure in which sugar is linked via ether bond to R[0012] 1, R2 or R3 positioned-alcoholic OH of dammarane aglycon, thereby interfering with penetration into stratum corneum and absorption into inner dermis.
  • While, extensive studies on saponin metabolites revealed that the efficacy of ginseng saponin is due to the metabolites decomposed by human intestinal bacteria, not due to saponin itself. For example, ginsenoside-Rh1, Rh2 and F1, compound K and others with one glucose linked to aglycon of saponin have been reported to have pharmacological effects such as inhibitions of proliferations of cancerous cells and tumors, and enlargement of activities of anticancer agents. [0013]
  • Neverthless, methods for application onto the skin and formulation of the compound K, ginsenoside F1 and compound Y obtained by removing a part of sugar moiety from ginseng saponin have not been researched yet. [0014]
  • Under these circumstances, in order to find a method for application of the compound K, ginsenoside F1 and compound Y onto the skin, the present inventors have conducted extensive studies on micro- and nano-emulsification. As a result thereof, the inventors found that nanoemulsion, obtained by emulsifying metabolites of ginseng saponin in fine emulsion or liposome with dermotropic emulsifier by nano-emulsification, has enhanced skin penetration and thereby can be applied to skin-care compositions for anti-aging. The present cosmetic composition containing the nanoemulsion can promote proliferation of fibroblast and biosynthesis of collagen, so to effectively prevent skin aging. [0015]
  • SUMMARY OF THE INVENTION
  • Therefore, an object of the invention is to provide a nanoemulsion comprising metabolites of ginseng saponin and having enhanced skin penetration. [0016]
  • Further, another object of the present invention is to provide a method for preparing the nanoemulsion. [0017]
  • A further object of the present invention is to provide a skin-care composition for anti-aging containing the nanoemulsion, which can promote fibroblast-proliferation and collagen-biosynthesis. [0018]
  • The nanoemulsion of the present invention comprises main metabolites of ginseng saponin obtained by conversion of glucose, i.e. compound K, ginsenoside F1, compound Y, or admixture thereof. The present nanoemulsion may be prepared by emulsifying metabolites of ginseng saponin in fine emulsion or liposome with dermotropic emulsifier by nano-emulsification. The present nanoemulsion has enhanced skin penetration and thereby the cosmetic composition containing the same can promote proliferation of fibroblast and biosynthesis of collagen, so to effectively prevent skin aging. [0019]
  • These and other objects and advantages of the invention will become apparent to those skilled in the art from the following detailed description with reference to the accompanying drawings.[0020]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a structural photograph of epidermal cells showing the effect of Formulation 7 on biosynthesis of collagen. [0021]
  • FIG. 2 is a structural photograph of epidermal cells showing the effect of Comparative Formulation 4 on biosynthesis of collagen. [0022]
  • FIG. 3 is a structural photograph of epidermal cells showing the effect of Example 2 on biosynthesis of collagen. [0023]
  • FIG. 4 is a structural photograph of epidermal cells showing the effect of Example 3 on biosynthesis of collagen. [0024]
  • FIG. 5 is a structural photograph of epidermal cells showing the effect of Example 4 on biosynthesis of collagen. [0025]
  • FIG. 6 is a structural photograph of epidermal cells showing the effect of Comparative Example 1 on biosynthesis of collagen.[0026]
  • DETAILED DESCRIPTION OF THE INVENTION
  • The following is a detailed description of the present invention. [0027]
  • The present invention relates to nanoemulsion comprising, as an effective component, metabolites of ginseng saponin obtained by conversion of glucose (via acid or alkaline hydrolysis or enzyme reaction). The present nanoemulsion of the present invention comprises at least on selected from the group consisting of compound K (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol), ginsenoside F1 (20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol), compound Y (20-O-[α-L-arabinopyranosyl(1→6)-β-D-glucopyranosyl]-20(S)-protopanaxadiol) and admixture thereof. [0028]
  • Hereinafter, the above admixture of metabolites that comprising compound K, ginsenoside F1 and compound Y as main components is called as “Bio GF1K”. In the present invention, Bio GF1K may be preferable in that it may not need further purification into each metabolite. More particularly, Bio GF1K may be admixture of metabolites obtained by conversion of glucose (via acid or alkaline hydrolysis or enzyme reaction) from purified ginseng saponin, comprising 30˜50 wt % of compound K, 5˜25 wt % of ginsenoside F1 and 5˜25 wt % of compound Y. [0029]
  • The present nanoemulsion may be prepared by emulsifying metabolites of ginseng saponin into fine emulsion or liposome, using nano-emulsification. More particularly, the present nanoemulsion may be prepared by emulsifying metabolites of ginseng saponin into fine emulsion or liposome with dermotropic emulsifier such as lecithin or its derivatives, by nano-emulsification such as homogenization or solvent extraction. The obtained nanoemulsion has enhanced skin penetration and thereby the skin-care composition containing the same can promote proliferation of fibroblast and biosynthesis of collagen, so as to be superior in preventing skin aging. [0030]
  • Said compound K is represented by the following formula 1: [0031]
    Figure US20030175315A1-20030918-C00001
  • (wherein, R[0032] 1 is O-Glc, R2 is OH and R3 is H).
  • Said ginsenoside F1 is represented by the following formula 2: [0033]
    Figure US20030175315A1-20030918-C00002
  • (wherein, R[0034] 1 is O-Glc, R2 is OH and R3 is OH).
  • Said compound Y is represented by the following formula 3: [0035]
    Figure US20030175315A1-20030918-C00003
  • (wherein, R[0036] 1 is O-Glc6-1Arap, R2 is OH and R3 is H).
  • Preferably, said Bio GF1K comprises 30˜50 wt % of compound K represented by the formula 1, 5˜25 wt % of ginsenoside F1 represented by the formula 2 and 5˜25 wt % of compound Y represented by the formula 3 as main components. [0037]
  • In general, hydrophobic material is more effective in skin penetration than hydrophilic one. This is because of intercellular lipids such as ceramide distributed in stratum corneum of the epidermis. Hydrophobic material has reciprocity with intercellular lipids, thereby passing through the outermost layer of the epidermis more easily. As the above formula 1 to 3 show, said compound K, gensenoside F1 and compound Y have reduced molecular weight and are hydrophobic by removing a part of sugar moiety from ginseng saponin, resulting in enhancement of skin penetration. [0038]
  • In the present invention, Bio GF1K may be prepared by removing a part of sugar moiety from ginseng saponin via acid or alkaline hydrolysis or enzyme reaction and then by passing through silica gel column. Further, Bio GF1K may be fractionated by changing the polarity of eluent on silica gel column and then separated into each metabolite of ginseng saponin on TLC. [0039]
  • An enzyme employed in the present invention may be β-glucosidase, which hydrolyzes sugar bond linked to saponin; α,β-arabinosidase, α,β-rhamnosidase, which hydrolyze exo sugar; and enzyme complex thereof. [0040]
  • Metabolites of ginseng saponin may be incorporated into the present nanoemulsion in an amount of 10˜50% by weight based on the total weight of nanoemulsion. More preferably, metabolites may be incorporated in an amount of 0.001˜30 wt %. [0041]
  • Further, the present nanoemulsion may be incorporated into a skin-care composition in an amount of 10[0042] −10˜50% by weight based on the total weight of composition, depending on a method of preparation thereof. If the amount is less than 1010 wt %, it may be difficult to obtain the aimed effect. While, if the amount is more than 50 wt %, there may be a problem in stability of formulation.
  • The present nanoemulsion may have the diameter of 30˜500 nm, more preferably 50˜300 nm. As a result, the present nanoemulsion can increase a surface contacting with the skin in comparison with conventional emulsion having the diameter of 500 nm or more and thereby can increase area for skin penetration. Additionally, in consideration that gap-size of intercellular lipids in stratum corneum is about 50 nm and that emulsified film of emulsion is soft and flexible, the present nanoemulsion can be easily absorbed and spread into intercellular lipids. That is, through two routes, one of which is increased contact surface with the skin and the other of which is increased permeation and spread into intercellular lipids, the present nanoemulsion having the diameter of 30˜500 nm obtained by nano-emulsification can enhance skin penetration thereof and of metabolites contained therein as an effective component. [0043]
  • Further, a lecithin employed in the present invention as an emulsifier is liposome containing one or more selected from the group consisting of unsaturated choline compound such as phosphatidylcholine and lysophosphatidylcholine; serine compound; cephalin compound such as phosphatidylethanolamine; and hydrogenated compound thereof. It may be employed in an amount of 0.5˜10%, more preferably 2˜5% by weight based on the total weight of nanoemulsion. [0044]
  • Further, supplementary emulsifier such as anionic, cationic, nonionic or amphoteric emulsifier may be employed together with lecithin in a ratio of 0.5˜5 times, more preferably 1˜3 times based on the weight of lecithin. [0045]
  • In addition, as a nano-emulsification, homogenization (under 500˜2,500 bar) or solvent extraction may be employed. [0046]
  • The obtained nanoemulsion may be incorporated into a skin-care composition for anti-aging. The present composition may be formulated, but not limited thereto, into cosmetic composition such as skin softeners, astringents, nutrient toilet water, nutrient creams, massage creams, essences, eye creams, eye essences, cleansing creams, cleansing foams, cleansing water, packs, powders, body lotions, body creams, body oils, body essences, make-up bases, foundation, hairdyes, shampoos, rinses, body cleansers, toothpastes and oral cleaning fluid; and pharmaceutical composition such as lotions, ointments, gels, creams, patches and sprays. Also, the composition may further incorporate other ingredients depending on the formulation or the final purposes thereof. [0047]
  • PREFERRED EMBODIMENT OF THE INVENTION
  • The present invention will be described in more detail by way of the following examples, which should not be considered to limit the scope of the present invention. [0048]
  • REFERENCE EXAMPLE 1 Preparation of Purified Ginseng Saponin
  • To 2 kg of red ginseng, 4 l of distilled water and ethanol containing water were added and then refluxed three (3) times. The crude extract was settled down at a temperature of 15° C. for 6 days, and then filtered and centrifuged to remove residue. After, the filtrate (extract) was concentrated under reduced pressure. The concentrated extract was suspended in water and then extracted with 1 l of ether five(5) times to remove pigment. The aqueous part was extracted with 500 ml of 1-butanol three(3) times. All the 1-butanol parts were treated with 5% KOH and washed with distilled water, and then concentrated under reduced pressure to obtain 1-butanol extract. The extract was dissolved in a small quantity of methanol and added to a large quantity of ethylacetate. The obtained precipitate was dried, to give 100 g (yield: 5%) of purified ginseng saponin. [0049]
  • REFERENCE EXAMPLE 2 Preparation of Bio GF1K via Acid Hydrolysis
  • To 10 g of purified ginseng saponin obtained in Reference Example 1, twenty (20) times (v/w) of 7% sulfuric acid/50% ethanol(v/w) mixture was added, and then refluxed in 100° C. of water bath for 6 hours to hydrolyze sugar-bond linked to ginseng saponin. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was suspended in 1,000 ml of distilled water and then extracted with same quantity of ether three (3) times. All the ether parts were washed with distilled water, dehydrated over magnesium sulfate anhydride(MgSO[0050] 4), filtered and then concentrated, to give crude product. The crude product was fractionated on silica gel column chromatography (as an eluent, chloroform:methanol=9:1→4:1), to give 210 mg (yield: 2%) of Bio GF1K comprising 70 mg of compound K, 30 mg of ginsenoside F1 and 35 mg of compound Y as main components.
  • Further, each fraction was subjected to thin-layer chromatography (chloroform/methanol/distilled water=65/35/10), to give 70 mg of compound K (Rf=0.73), 30 mg of ginsenoside F1 (Rf-0.65) and 35 mg of compound Y (Rf=0.49). [0051]
  • REFERENCE EXAMPLE 3 Preparation of Bio GF1 K via Alkaline Hydrolysis
  • 10 g of purified ginseng saponin obtained in Reference Example 1 was dissolved in 500 ml of dried pyridine. Thereto was added sodium methoxide (powder, 10 g) and then refluxed in oil bath for 8 hours, to hydrolyze sugar-bond linked to ginseng saponin. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was suspended in 1,000 ml of distilled water and then extracted with same quantity of ether three (3) times. All the ether parts were washed with distilled water, dehydrated over magnesium sulfate anhydride(MgSO[0052] 4), filtered and then concentrated, to give crude product. The crude product was fractionated on silica gel column chromatography (as an eluent, chloroform:methanol=9:1→4:1), to give 205 mg (yield: 2%) of Bio GF1K comprising 75 mg of compound K, 35 mg of ginsenoside F1 and 30 mg of compound Y.
  • Then, each fraction was subjected to thin-layer chromatography (chloroform/methanol/distilled water=65/35/10), to give 75 mg of compound K (Rf=0.73), 35 mg of ginsenoside F1 (Rf=0.65) and 30 mg of compound Y (Rf=0.49). [0053]
  • Reference Example 4-1 Preparation of Bio GF1K via Enzyme Reaction
  • 10 g of purified ginseng saponin obtained in Reference Example 1 was dissolved in 100 ml of citrate buffer (pH 5.5). Thereto was added 1 g of naringinase separated from Penicillium and then stirred in 40° C. of water bath for 48 hours. The reaction was checked periodically on TLC (thin-layer chromatography). When the substrate was completely consumed, the reaction was terminated by heating in hot water for 10 minutes. The reaction mixture was extracted with same quantity of ether three (3) times, and then concentrated. The obtained product was fractionated on silica gel column chromatography (as an eluent, chloroform:methanol=9:1→4:1), to give 1,050 mg (yield: 10.5%) of Bio GF1K comprising 440 mg of compound K, 150 mg of ginsenoside F1 and 140 mg of compound Y (Rf=0.49). [0054]
  • Then, each fraction was subjected to thin-layer chromatography (chloroform/methanol/distilled water=65/35/10), to give 440 mg of compound K (Rf=0.73), 150 mg of ginsenoside F1 (Rf=0.65) and 140 mg of compound Y (Rf=0.49). [0055]
  • In addition, the following enzyme reactions may be utilized for the preparation of the present Bio GF1K. [0056]
  • Reference Example 4-2
  • 10 g of purified ginseng saponin was dissolved in 100 ml of citrate buffer containing 15% ethanol (pH 4.0). Thereto was added 0.5 g of naringinase separated from Penicillium and then stirred in 40° C. of water bath for 48 hours. The reaction was checked periodically on TLC (thin-layer chromatography). When the substrate was completely consumed, the reaction was terminated by heating in hot water for 10 minutes. The reaction mixture was extracted with same quantity of ethyl acetate three (3) times, and then concentrated. The obtained product was fractionated on silica gel column chromatography (as an eluent, chloroform:methanol=9:1→4:1), to give 373 mg (yield: 3.73%) of Bio GF1K comprising 150 mg of compound K, 100 mg of ginsenoside F1 and 102 mg of compound Y. [0057]
  • Then each fraction was subjected to thin-layer chromatography (chloroform/methanol/distilled water=65/35/10), to give 150 mg of compound K (Rf=0.73), 100 mg of ginsenoside F1 (Rf=0.65) and 102 mg of compound Y (Rf=0.49). [0058]
  • Reference Example 4-3
  • 10 g of purified ginseng saponin was dissolved in 100 ml of citrate buffer containing 15% ethanol (pH 4.0). Thereto was added 2 g of pectinase separated from Aspergillus and then stirred in 30° C. of water bath for 48 hours. The reaction was checked periodically on TLC (thin-layer chromatography). When the substrate was completely consumed, the reaction was terminated by heating in hot water for 10 minutes. The reaction mixture was extracted with same quantity of ethyl acetate three (3) times, and then concentrated. The obtained product was fractionated on silica gel column chromatography (as an eluent, chloroform:methanol=9:1→4:1), to give 190 mg (yield: 1.9%) of Bio GF1K comprising 80 mg of compound K, 30 mg of ginsenoside F1 and 35 mg of compound Y. [0059]
  • Then, each fraction was subjected to thin-layer chromatography (chloroform/methanol/distilled water=65/35/10), to give 80 mg of compound K (Rf=0.73), 30 mg of ginsenoside F1 (Rf=0.65) and 35 mg of compound Y (Rf=0.49). [0060]
  • Reference Example 4-4
  • 10 g of purified ginseng saponin was dissolved in 100 ml of citrate buffer (pH 5.5). Thereto was added 2 g of pectinase separated from Aspergillus and then stirred in 30° C. of water bath for 48 hours. The reaction was checked periodically on TLC (thin-layer chromatography). When the substrate was completely consumed, the reaction was terminated by heating in hot water for 10 minutes. The reaction mixture was extracted with same quantity of ether three (3) times, and then concentrated. The obtained product was fractionated on silica gel column chromatography (as an eluent, chloroform:methanol=9:1→4:1), to give 493 mg (yield: 4.93%) of Bio GF1K comprising 180 mg of compound K, 82 mg of ginsenoside F1 and 85 mg of compound Y. [0061]
  • Then, each fraction was subjected to thin-layer chromatography (chloroform/methanol/distilled water=65/35/10), to give 180 mg of compound K (Rf=0.73), 82 mg of ginsenoside F1 (Rf=0.65) and 85 mg of compound Y (Rf=0.49). [0062]
  • In the following Examples 1˜6, the present nanoemulsions were prepared by comprising said compound K, ginsenoside F1 and compound Y obtained in said Reference Examples. Each ingredient and its amount are specified in Table 1. [0063]
  • EXAMPLE 1
  • Bio GF1K comprising compound K, ginsenoside F1 and compound Y was added to the solution containing lecithin, hydrogenated lecithin, cholesterol, soy oil and propylene glycol, and then heated to a temperature of 70˜75° C. to be completely dissolved. Then, it was mixed with pre-heated aqueous parts (distilled water, EDTA) and pre-emulsified under 3,000˜6,000 rpm for 3 minutes with general homomixer. Subsequently, it was emulsified under 1,000 Bar/3 cycles with Microfluidizer. [0064]
  • Among said ingredients, hydrogenated lecithin has good emulsion-stabilizing efficiency. But, it is an inferior dermotropic to unsaturated lecithin and thereby exhibits poor skin penetration. Therefore, in this example, two kinds of lecithin were admixed. [0065]
  • EXAMPLE 2
  • The procedure described in Example 1 was followed by using compound K instead of Bio GF1K. [0066]
  • EXAMPLE 3
  • The procedure described in Example 1 was followed by using ginsenoside F1, instead of Bio GF1K. [0067]
  • EXAMPLE 4
  • The procedure described in Example 1 was followed by using compound Y, instead of Bio GF1K. [0068]
  • EXAMPLE 5
  • Lecithin, PEG-5 grapeseed sterol, capric/caprylic triglyceride, BHT, α-tocopherol and pentylene glycol were dissolved in ethanol. Thereto was added Bio GF1K and then heated to a temperature of 70˜75° C. to be completely dissolved. Then, it was mixed with pre-heated aqueous parts (distilled water, EDTA) and pre-emulsified under 3,000˜6,000 rpm for 3 minutes with general homomixer. Subsequently, it was emulsified under 1,000 Bar/3 cycles with Microfluidizer. [0069]
  • Among said ingredients, BHT as an antioxidant was added in order to complement chemical instability of unsaturated lecithin. Further, PEG-5 grapeseed sterol as a supplementary emulsifier was added in order to increase emulsion-stability. [0070]
  • EXAMPLE 6
  • Hydrogenated lecithin, hydrogenated lysophosphatidyl choline (HLPC) and propylene glycol were dissolved in ethanol. Thereto was added Bio GF1K and then heated to a temperature of 70˜75° C. to be completely dissolved. Then, it was mixed with pre-heated aqueous parts (distilled water, EDTA, glycerin, betain) and pre-emulsified under 3,000˜6,000 rpm for 3 minutes with general homomixer. Subsequently, it was emulsified under 1,000 Bar/3 cycles with Microfluidizer. [0071]
  • Among said ingredients, hydrogenated lysophosphatidyl choline(HLPC) is obtained by hydrolyzing hydrogenated phosphatidyl choline (HPC) which constitutes hydrogenated lecithin. It is superior to HPC in emulsibility. [0072]
  • In order to compare the nanoemulsion obtained in Examples 1˜6 with purified ginseng saponin in skin penetration, Comparative Examples 1˜3 were prepared by comprising purified ginseng saponin and the ingredients specified in Table 1. [0073]
  • COMPARATIVE EXAMPLE 1
  • The procedure described in Example 1 was followed by emulsifying purified ginseng saponin prepared by Reference Example 1, instead of emulsifying Bio GF1K. [0074]
  • COMPARATIVE EXAMPLE 2
  • The procedure described in Example 5 was followed by emulsifying purified ginseng saponin prepared by Reference Example 1, instead of emulsifying Bio GF1K. [0075]
  • COMPARATIVE EXAMPLE 3
  • The procedure described in Example 6 was followed by emulsifying purified ginseng saponin prepared by Reference Example 1, instead of emulsifying Bio GF1K. [0076]
  • EXAMPLE 7
  • The procedure described in Example 5 was followed by using compound K instead of Bio GF1K. [0077]
  • EXAMPLE 8
  • The procedure described in Example 5 was followed by using ginsenoside F1, instead of Bio GF1K. [0078]
  • EXAMPLE 9
  • The procedure described in Example 5 was followed by using compound Y, instead of Bio GF1K. [0079]
  • EXAMPLE 10
  • The procedure described in Example 6 was followed by using compound K instead of Bio GF1K. [0080]
  • EXAMPLE 11
  • The procedure described in Example 6 was followed by using ginsenoside F1, instead of Bio GF1K. [0081]
  • EXAMPLE 12
  • The procedure described in Example 6 was followed by using compound Y, instead of Bio GF1K. [0082]
  • The above examples 7 to 12 are not shown in the table 1. [0083]
    TABLE 1
    (Unit: wt %)
    Examples C. Examples
    Ingredients 1 2 3 4 5 6 1 2 3
    Hydrogenated lecithin 1.5 1.5 1.5 1.5 2.5 1.5 2.5
    Lecithin 3.0 3.0 3.0 3.0 2.0 3.0 2.0
    PEG-5 grapeseed sterol 4.0 4.0
    Capric/caprylic triglyceride 7.5 7.5
    Hydrogenated lysophosphatidyl  0.15  0.15
    Cholesterol 1.5 1.5 1.5 1.5 1.5
    Soy oil 7.5 7.5 7.5 7.5 7.5
    Pentylene glycol 5.0 5.0
    Propylene glycol 5.0 5.0 5.0 5.0 4.0 5.0 4.0
    Ethanol 7.5 6.5 7.5 6.5
    Bio GF1K 1.5 1.5 1.5
    Compound K 1.5
    Ginsenoside F1 1.5
    Compound Y 1.5
    Purified ginseng saponin 1.5 1.5 1.5
    α-tocopherol 0.2 0.2
    Butylated hydroxy toluene (BHT)  0.01  0.01
    Distilled water to to to to to to to to to
    EDTA  0.05  0.05  0.05  0.05  0.05  0.05  0.05  0.05  0.05
    Glycerin 4.0 4.0
    Betain 1.0 1.0
  • In addition, in order to confirm enhancement in skin penetration of nanoemulsion prepared by dermotropic emulsifier and nano-emulsification, Comparative Example 4 was prepared by dissolving 1.5 wt % of Bio GF1K obtained in Reference Example 4-1 in ethanol solution, Comparative Example 5 was prepared by dissolving 1.5 wt % of Bio GF1K in propylene glycol/ethanol solution and Comparative Example 6 was prepared by dissolving 1.5 wt % of Bio GF1K in pentylene glycol/ethanol solution. [0084]
  • Also, Comparative Example 7 was prepared by dissolving 1.5 wt % of purified ginseng saponin in ethanol solution, Comparative Example 8 was prepared by dissolving 1.5 wt % of purified ginseng saponin in propylene glycol/ethanol solution and Comparative Example 9 was prepared by dissolving 1.5 wt % of purified ginseng saponin in pentylene glycol/ethanol solution. C. Examples 4˜9 are presented in Table 2. [0085]
    TABLE 2
    Ingredient Amount Diluent
    C. Ex. 4 Bio GF1K 1.5 wt % Ethanol
    C. Ex. 5 Bio GF1K 1.5 wt % Propylene glycol/
    Ethanol(4.0/6.5)
    C. Ex. 6 Bio GF1K 1.5 wt % Pentylene glycol/
    Ethanol(5.0/7.5)
    C. Ex. 7 Purified ginseng saponin 1.5 wt % Ethanol
    C. Ex. 8 Purified ginseng saponin 1.5 wt % Propylene glycol/
    Ethanol(4.0/6.5)
    C. Ex. 9 Purified ginseng saponin 1.5 wt % Pentylene glycol/
    Ethanol(5.0/7.5)
  • In addition, the present nanoemulsion was formulated into the following skin-care compositions. In Tables 3˜7, unit is wt %. [0086]
  • <Formulation: Cream> [0087]
    TABLE 3
    Formulation C. Formulations
    Materials 1 2 3 4 5 6 1 2 3
    Nanoemulsion of Ex. 1 10.0 
    Nanoemulsion of Ex. 2 10.0 
    Nanoemulsion of Ex. 3 10.0 
    Nanoemulsion of Ex. 4 10.0 
    Nanoemulsion of Ex. 5 10.0 
    Nanoemulsion of Ex. 6 10.0 
    Nanoemulsion of C. Ex. 1 10.0 
    Nanoemulsion of C. Ex. 2 10.0 
    Nanoemulsion of C. Ex. 3 10.0 
    Beeswax 10.0  10.0  10.0  10.0  10.0  10.0  10.0  10.0  10.0 
    Polysorbate-60 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
    Sorbitan sesquioleate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
    PEG-60 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
    hydrogenated castor oil
    Liquid paraffin 10.0  10.0  10.0  10.0  10.0  10.0  10.0  10.0  10.0 
    Squalane 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
    Capric/caprylic 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
    triglyceride
    Glycerin 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
    Butylene glycol 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0
    Propylene glycol 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0
    Triethanolamine 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
    Preservative q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Pigments q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Perfume q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Distilled water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100
  • <Formulation: Nutrient Water> [0088]
    TABLE 4
    Formulations C. Formulations
    Materials 7 8 9 10 11 12 4 5 6
    Nano emulsion of Ex. 1 10.0 
    Nano emulsion of Ex. 2 10.0 
    Nano emulsion of Ex. 3 10.0 
    Nano emulsion of Ex. 4 10.0 
    Nano emulsion of Ex. 5 10.0 
    Nano emulsion of Ex. 6 10.0 
    Nano emulsion of C. Ex. 1 10.0 
    Nano emulsion of C. Ex. 2 10.0 
    Nano emulsion of C. Ex. 3 10.0 
    Cetyl ethyl hexanoate 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
    Cetostearyl alcohol 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
    Lipophilic 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8
    monostearic stearate
    Squalane 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
    Polysorbate-60 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
    Sorbitan sesquioleate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
    Glycerin 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
    Triethanol amine 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
    Carboxyvinyl polymer 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
    Preservative q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Pigments q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Perfume q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Distilled water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100
  • <Formulation: Skin Softener> [0089]
    TABLE 5
    Formulations C. Formulations
    Materials 13 14 15 16 17 18 7 8 9
    Nano emulsion of Ex. 1 10.0 
    Nano emulsion of Ex. 2 10.0 
    Nano emulsion of Ex. 3 10.0 
    Nano emulsion of Ex. 4 10.0 
    Nano emulsion of Ex. 5 10.0 
    Nano emulsion of Ex. 6 10.0 
    Nano emulsion of C. Ex. 1 10.0 
    Nano emulsion of C. Ex. 2 10.0 
    Nano emulsion of C. Ex. 3 10.0 
    Betain 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0
    Natogum 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0
    Cellulose gum  0.08  0.08  0.08  0.08  0.08  0.08  0.08  0.08  0.08
    Ethanol 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
    Polyoxyethylene 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
    hydrogenated castor oil
    Tocopheryl acetate 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
    Preservative q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Pigments q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Distilled water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100
  • <Formulation: Gel> [0090]
    TABLE 6
    Formulations C. Formulations
    Materials 19 20 21 22 23 24 10 11 12
    Nano emulsion of Ex. 1 10.0 
    Nano emulsion of Ex. 2 10.0 
    Nano emulsion of Ex. 3 10.0 
    Nano emulsion of Ex. 4 10.0 
    Nano emulsion of Ex. 5 10.0 
    Nano emulsion of Ex. 6 10.0 
    Nano emulsion of C. Ex. 1 10.0 
    Nano emulsion of C. Ex. 2 10.0 
    Nano emulsion of C. Ex. 3 10.0 
    EDTA · 2Na  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.02
    Ethoxy glycol  1.00  1.00  1.00  1.00  1.00  1.00  1.00  1.00  1.00
    Polyacrylate 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00
    Ethanol 30.00 30.00 30.00 30.00 30.00 30.00 30.00 30.00 30.00
    Hydrogenated castor oil  0.80  0.80  0.80  0.80  0.80  0.80  0.80  0.80  0.80
    Phenyl trimethicone  0.20  0.20  0.20  0.20  0.20  0.20  0.20  0.20  0.20
    Triethanol amine  0.40  0.40  0.40  0.40  0.40  0.40  0.40  0.40  0.40
    Perfume q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
    Distilled water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100
  • <Formulaion: Ointment> [0091]
    TABLE 7
    Formulations C. Formulations
    Materials 25 26 27 28 29 30 13 14 15
    Nano emulsion of Ex. 1 10.0
    Nano emulsion of Ex. 2 10.0
    Nano emulsion of Ex. 3 10.0
    Nano emulsion of Ex. 4 10.0
    Nano emulsion of Ex. 5 10.0
    Nano emulsion of Ex. 6 10.0
    Nano emulsion of C. Ex.1 10.0
    Nano emulsion of C. Ex. 2 10.0
    Nano emulsion of C. Ex. 3 10.0
    Capric/caprylic 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0
    triglyceride
    Liquid paraffin 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0
    Sorbitan sesquioleate  6.0  6.0  6.0  6.0  6.0  6.0  6.0  6.0  6.0
    Octyl dodeses-25  9.0  9.0  9.0  9.0  9.0  9.0  9.0  9.0  9.0
    Cetyl ethyl hexanoate 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0
    Squalane  1.0  1.0  1.0  1.0  1.0  1.0  1.0  1.0  1.0
    Salicylic acid  1.0  1.0  1.0  1.0  1.0  1.0  1.0  1.0  1.0
    Glycerin 15.0 15.0 15.0 15.0 15.0 15.0 15.0 15.0 15.0
    Sorbitol 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0
    Distilled water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100
  • EXPERIMENTAL EXAMPLE 1 Effect on Skin Penetration
  • Skin penetration was evaluated for Guinea pig's skin with Frantz cell. Before test, abdominal part, a piece of skin as large as 1 cm[0092] 2 square was excised. The excised skin was mounted on a Frantz cell with the diameter of 0.9 cm and fixed with clamp. 0.5 ml of test sample (in case of Examples 1˜9 and C. Examples 1˜6, 0.05 ml of sample and distilled water; and in case of Formulations 1˜30 and C. Formulations 1˜15, 0.5 ml of sample only) was placed on one side of skin (donor side). The other side (receiver side) was filled with mixture of distilled water and ethanol (4:1 weight ratio). Test was performed at 32° C., which is skin temperature. Test solvent was sampled at predetermined time intervals from the receiver side, and the amounts of penetrated compound K, ginsenoside F1 and compound Y were determined by HPLC system. The data were indicated in penetrated amount per applied concentration (μg/cm2/wt %). The results are shown in Table 8a and Table 8b.
  • In case of purified ginseng saponin, the amount of penetrated saponin was determined. Also, in case of Bio GF1K, the amounts of penetrated compound K, ginsenoside F1 and compound Y were determined and total penetrated amounts were calculated by sum of each peak. [0093]
  • <HPLC Analytic Condition>[0094]
  • Column: C18(ODS) [0095]
  • Solvent Flow: 1 ml/min [0096]
  • Detection UV: 203 nm [0097]
  • Sample test concentration: 5 mg/ml [0098]
  • Sample injection amount: 10 μg [0099]
  • Eluent: Gradient condition [0100]
  • A: Acetonitrile/D.I. water=15/85 [0101]
  • B: Acetonitrile/D.I. water=80/20 [0102]
  • <Solvent Gradient Condition> [0103]
    Time (min) A (%) B (%)
    0 100
    10 70 30
    25 50 50
    40 100
    70 100
  • [0104]
    TABLE 8a
    Penetrated amounts during elapsed time
    (of Examples 1˜12 and C. Examples 1˜9)
    Ex-
    am- Elapsed time (hr) Comparative Elapsed time (hr)
    ples 0 4 8 12 Examples 0 4 8 12
    1 0 15.15 29.98 50.13 1 0 3.52 7.11 15.41
    2 0 15.15 29.98 50.13 2 0 3.66 7.35 15.06
    3 0 15.45 39.74 58.43 3 0 3.35 7.04 14.95
    4 0 15.15 28.98 33.13 4 0 1.42 1.75 2.45
    5 0 16.02 32.14 52.21 5 0 1.32 1.68 2.38
    6 0 14.59 31.25 49.32 6 0 1.51 1.75 2.55
    7 0 16.02 32.14 52.21 7 0 0.15 0.45 0.95
    8 0 13.02 38.64 55.27 8 0 0.20 0.50 1.02
    9 0 16.02 26.14 34.21 9 0 0.18 0.43 0.93
    10 0 14.59 31.25 49.32
    11 0 12.59 33.55 45.32
    12 0 14.59 20.25 25.32
  • [0105]
    TABLE 8b
    Penetrated amounts during elasped time
    (of Formulations 1˜30 and C. Formulations 1˜15)
    For-
    mula- Elapsed time (hr) Comparative Elapsed time (hr)
    tions 0 4 8 12 Formulation 0 4 8 12
    1 0 12.12 31.00 50.21 1 0 3.51 6.98 14.68
    5 0 1.21 1.69 2.44 2 0 0.12 0.42 0.86
    6 0 2.21 3.86 5.40 3 0 0.48 1.01 2.03
    7 0 15.98 31.86 51.97 4 0 3.62 7.21 14.93
    11 0 1.25 1.61 2.21 5 0 0.14 0.43 0.90
    12 0 2.24 3.75 5.11 6 0 0.45 0.97 1.97
    13 0 14.30 28.59 49.99 7 0 3.23 6.84 13.83
    17 0 1.25 1.75 2.35 8 0 0.16 0.47 0.91
    18 0 2.23 3.65 5.06 9 0 0.50 1.03 2.11
    19 0 15.21 31.25 51.21 10 0 3.33 7.13 15.02
    23 0 1.22 1.85 2.54 11 0 0.16 0.43 0.92
    24 0 2.12 3.36 5.35 12 0 0.49 1.11 2.23
    25 0 12.13 30.99 51.85 13 0 3.45 7.10 16.02
    29 0 1.23 1.87 2.13 14 0 0.12 0.44 0.93
    30 0 2.23 3.45 5.61 15 0 0.48 0.96 2.06
    2 0 12.12 31.00 50.21
    3 0 12.12 34.00 54.21
    4 0 12.12 24.00 35.21
    8 0 15.98 31.86 51.97
    9 0 15.98 37.86 57.93
    10 0 15.98 31.86 31.97
    14 0 14.30 28.59 49.99
    15 0 14.30 38.59 59.97
    16 0 14.30 28.59 33.99
    20 0 15.21 31.25 51.21
    21 0 14.21 32.25 53.23
    22 0 15.21 31.25 31.21
    26 0 12.13 30.99 51.85
    27 0 12.13 35.99 57.83
    28 0 12.13 30.99 31.85
  • The result of said experiment confirmed that Examples 1˜12, i.e. nanoemulsions prepared by applying nano-emulsification to metabolites of ginseng saponin, exhibited dramatic enhancement in skin penetration compared with the C. Examples. For reference, within the C. Examples, C. Examples 1˜3, i.e. nanoemulsions prepared by nano-emulsification exhibited more effective skin penetration than C. Examples 4˜9, i.e. simple solutions prepared by dissolving each ingredient in solvent. [0106]
  • By the comparison of Examples and corresponding C. Examples, it was confirmed that metabolites of ginseng saponin, i.e. compound K, ginsenoside F1 and compound Y, exhibited superior effects on skin penetration to purified ginseng saponin. This may result from specific chemical structures of compound K, ginsenoside F1 and compound Y. [0107]
  • In summary, metabolites of ginseng saponin, i.e. compound K, ginsenoside F1 and compound Y exhibit more effective skin penetration than purified ginseng saponin, and particularly can enhance skin penetration by emulsifying with dermotropic lecithin by nano-emulsification. [0108]
  • Further, these results can be confirmed in Formulations 1˜30 and C. Formulations 1˜15, which were prepared by formulating Examples and C. Examples. That is, skin penetration of metabolites enhanced by dermotropic lecithin and nano-emulsification was confirmed as it was within the formulations. [0109]
  • As shown in Table 8b, in consideration that general duration of make-up is about 4˜8 hours, Examples and Formulations containing compound K, ginsenoside F1 and compound Y exhibit enhanced skin penetration 9˜10 times greater than C. Examples and C. Formulations containing purified ginseng saponin. [0110]
  • EXPERIMENTAL EXAMPLE 2 Effect on Proliferation of Fibroblast
  • Human fibroblasts were cultured on Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 3.5% fetal bovine serum. The fibroblasts were seeded into 96-well microtiter plate to a density of 5,000 cells/well. In case of nanoemulsions of Examples 1˜4 and of C. Example 1, test samples were prepared to adjust the concentrations of each metabolite, of Bio GF1K and of purified ginseng saponin to 1%. In case of cream of Formulations 1˜4 and of C. Formulation 1, for each 10% of solution was prepared as test sample. The test samples were added in consecutive dilutions of {fraction (1/10)} times with medium. Then, it was incubated at 37° C. for 4 days. After incubation, 0.2% of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) solution was added to each well, 50 μl per well, and then incubated again at 37° C. for 4 hours. The produced formazane was dissolved in dimethyl sulfoxide (DMSO) and the absorbance at 570 nm was measured with microplate reader. The proliferation of fibroblast was evaluated by comparing the absorbance with that of control group with no sample treated. The results are shown in Table 9. [0111]
    TABLE 9
    Concen- Proliferation of fibroblast (%)
    tration of Examples C. Formulations
    test sample 1 2 3 4 Ex. 1 1 2 3 4 C. Form 1
    1 × 10−8 5 5 5 5 3 5 6 5 5 3
    1 × 10−7 13 12 10 16 5 13 9 8 12 5
    1 × 10−6 25 23 25 28 8 24 21 22 23 8
    1 × 10−5 47 45 43 45 13 45 41 39 44 12
    1 × 10−4 54 71 75 54 19 51 69 65 52 18
    1 × 10−3 67 93 95 66 27 65 88 85 64 26
    1 × 10−2 81 120 121 81 41 79 112 102 78 40
    1 × 10−1 98 151 153 98 48 96 135 123 95 45
  • As shown in Table 9, nanoemulsions of Examples 1˜4 comprising the metabolites of ginseng saponin were more effective in proliferating fibroblast, in comparison with microemulsion of C. Example 1 comprising purified ginseng saponin. [0112]
  • Further, this result was confirmed in Formulations 1˜4 and C. Formulation 1, which were prepared by formulating Examples 1˜4 and C. Example 1. That is, Formulations 1˜4 were more effective in proliferating fibroblast than C. Formulation 1. [0113]
  • EXPERIMENTAL EXAMPLE 3 Effect on Proliferation of Keratinocyte
  • Proliferation of keratinocyte was evaluated by following same procedure described in Experimental Example 2. Test samples were prepared by employing Example 5, C. Example 2, Formulation 5 and C. Formulation 2, as described in Experimental Example 2. The results are shown in Table 10. [0114]
    TABLE 10
    Proliferation of keratinocyte (%)
    Concentration of C. C. Formu-
    Test sample (%) Example 5 Example 2 Formulation 5 lation 2
    1 × 10−8 5 4 5 4
    1 × 10−7 13 6 13 6
    1 × 10−6 18 7 18 7
    1 × 10−5 25 11 25 11
    1 × 10−4 34 14 34 14
    1 × 10−3 39 19 38 18
    1 × 10−2 45 23 44 21
    1 × 10−1 53 27 51 25
  • As shown in Table 10, the treatment with nanoemulsion of Example 5 comprising Bio GF1K led to about 2 times enhancement in proliferation of keratinocyte, in comparison with microemulsion of C. Example 2 comprising purified ginseng saponin. [0115]
  • Further, this result was confirmed in Formulation 5 and C. Formulation 2, which were prepared by formulating Example 5 and C. Example 2. [0116]
  • EXPERIMENTAL EXAMPLE 4 Effect on Biosynthesis of Collagen in vitro
  • Human fibroblasts were cultured on 24-well microtiter plate. As described in Experimental Example 2, in case of nanoemulsion of Example 6 and C. Example 3, test sample was added in consecutive dilutions of {fraction (1/100)} times with medium. In case of cream of Formulation 6 and C. Formulation 3, test sample was added in consecutive dilutions of {fraction (1/10)} times with medium. On the 3rd day, DMEM supplemented with 10% fetal bovine serum was added to each well, 0.5 ml per well, and then 10 μCi of L[2,3,4,5-3H]-proline was added. 24 hours later, the medium and the cells contained in each well were raked up and washed with 5% of trichloroacetic acid (TCA). Then, it was divided into two test tubes. 1 Unit/μl of type | collagenase was added to one tube and then incubated at 37° C. for 90 minutes. The other tube was incubated at 4° C. Then, 0.05 ml of 50% TCA was added to each tube and maintained at 4° C. for 20 minutes. The resulting solution was centrifuged at 12,000 rpm for 10 minutes. The decay per minute (dpm) of the supernatant and of the precipitate were measured with liquid scintillation counter (LSC). As to control group and test group, RCB (Relative Collagen Biosynthesis) value was calculated by the following equation 1. The results are shown in Table 11. [0117]
  • RCB=[collagen dpm/{(total collagen−collagen dpm)×5.4+collagen dpm}]×100  [Equation 1]
    TABLE 11
    Biosynthesis of collagen (%)
    Concentration of C. C. Formu-
    test sample (%) Example 6 Example 3 Formulation 6 lation 3
    1 × 10−8 5 2 2 3
    1 × 10−7 13 2 2 3
    1 × 10−6 25 4 4 6
    1 × 10−5 33 6 6 9
    1 × 10−4 51 10 10 13
    1 × 10−3 59 12 12 16
    1 × 10−2 68 16 15 20
    1 × 10−1 74 20 18 25
  • As shown in Table 11, the treatment with nanoemulsion of Example 6 comprising Bio GF 1K led to about 3 times enhancement in biosynthesis of collagen, in comparison with microemulsion of C. Example 3 comprising purified ginseng saponin. [0118]
  • Further, this result was confirmed in Formulation 6 and C. Formulation 3, which were prepared by formulating Example 6 and C. Example 3. [0119]
  • EXPERIMENTAL EXAMPLE 5 Effect on Biosynthesis of Collagen in vivo
  • Onto each back of hairless mice aging 42 weeks (female), Formulation 7 and C. Formulation 4 were applied in a vehicle of EtOH:PG=7:3 and patched for 3 days. After 24 hours of pause, patch was repeated for 3 days. Then, epidermal tissues were subjected to biopsy and then stained by immunohistochemical staining and haematoxylin-eosin staining for type | pN procollagen and MMP-1 (Matrix Metalloproteinase-1). Through the tissue-staining, expressions of procollagen and of MMP-1 and thickness of epidermis were observed and the results thereof were shown in FIG. 1 and FIG. 2. [0120]
  • In comparison of Formulation 7 with C. Formulation 4, as shown in FIG. 1 and FIG. 2, it can be confirmed that formulation of the present nanoemulsion is more effective in skin penetration of compound K, ginsenoside F1 and compound Y, so to promote biosynthesis of collagen. In case of C. Formulation 4, purified ginseng saponin is less effective in skin penetration, so to be insufficient in biosynthesis of collagen. This is because purified ginseng saponin has a structural difficulty in skin penetration, which cannot be overcome by dermotropic lecithin or by nano-emulsification. [0121]
  • In summary, said results confirm that metabolites of ginseng saponin, i.e. compound K, ginsenoside F1 and compound Y have a structural easiness in skin penetration, which can be maximized by dermotropic lecithin and nano-emulsification. That is, the present nanoemulsion can promote biosynthesis of collagen. [0122]
  • EXPERIMENTAL EXAMPLE 6 Effect on Biosynthesis of Collagen in vivo
  • The procedure described in Experimental Example 5 was followed by employing the nanoemulsions of Examples 2˜4 and of C. Example 1 as test samples, instead of formulation, to evaluate the effect on biosynthesis of collagen. The results were shown in FIG. 3, which shows the effect of Example 2 comprising compound K; in FIG. 4, which shows the effect of Example 3 comprising ginsenoside F1; in FIG. 5, which shows the effect of Example 4 comprising compound Y; and in FIG. 6, which shows the effect of C. Example 1 comprising purified ginseng saponin. [0123]
  • As explained in said Experimental Example 5, from the results of Experimental Example 1 and of Experimental Example 6, it can be confirmed that the present nanoemulsion comprising the metabolites of ginseng saponin, i.e. compound K, ginsenoside F1 or compound Y, is more effective in skin penetration, so to promote biosynthesis of collagen. On the contrary, the nanoemulsion comprising purified ginseng saponin is less effective in skin penetration, so to be insufficient in biosynthesis of collagen. This is because purified ginseng saponin has a structural difficulty in skin penetration, which cannot be overcome by dermotropic lecithin or by nano-emulsification. [0124]
  • EXPERIMENTAL EXAMPLE 7 Effect on Improvement of Skin Wrinkle
  • In order to evaluate the improvement of skin wrinkle for the composition containing the present nanoemulsion, four groups of volunteers aging 35˜45 years and having facial wrinkle, thirty (30) per group, used creams of Formulation 1 and of C. Formulation 1 (Group 1); creams of Formulation 2 and of C. Formulation 1 (Group 2); creams of Formulation 3 and of C. Formulation 1 (Group 3); and creams of Formulation 4 and of C. Formulation 1 (Group 4), for 3 months. To the left face was applied the cream of Formulation and to right face was applied the cream of C. Formulation 1. The improvement of skin wrinkle was evaluated by comparing the wrinkles of eye-tail before and after using the cream. The wrinkles of eye-tail were taken with replica and measured with visiometer system (C+K) in constant temperature and humidity room set to a temperature of 24° C. and relative humidity of 40%. The improvement of skin wrinkle was calculated by the following equation 2. The results are shown in Table 12. [0125]
  • Improvement of skin wrinkle (Δ%)={(Td i −Td 0)/Td 0}×100  [Equation 2]
  • (wherein, Td[0126] i is skin-wrinkle value measured after using the cream for 3 months, Td0 is skin-wrinkle value measured before using the cream).
    TABLE 12
    Wrinkle reduction
    (Δ %)
    Group 1 Formulation 1 63 ± 15%
    (containing nanoemulsion of Bio GF1K)
    Comparative Formulation 1 25 ± 10%
    (containing nanoemulsion of ginseng
    saponin)
    Group 2 Formulation 2 66 ± 15%
    (containing nanoemulsion of compound K)
    Comparative Formulation 1 22 ± 10%
    Group 3 Formulation 3 72 ± 15%
    (containing nanoemulsion of ginsenoside F1)
    Comparative Formulation 1 23 ± 10%
    Group 4 Formulation 4 56 ± 15%
    (containing nanoemulsion of compound Y)
    Comparative Formulation 1 21 ± 10%
  • As above described, the nanoemulsion of the present invention comprises compound K, ginsenoside F1 or compound Y which have a structural effectiveness in skin penetration by removing a part of sugar moiety from ginseng saponin. Further, the present nanoemulsion has skin penetration enhanced by dermotropic emulsifier and nano-emulsification, and thereby can promote proliferation of fibroblast and biosynthesis of collagen, so to be used extensively in preventing skin-wrinkle and skin-aging. [0127]
  • Although preferred embodiments of the present invention have been described in detail above, it should be clearly understood that many variations of the basic inventive concepts herein taught which may appear to those skilled in the art will still fall within the spirit and scope of the present invention as defined in the appended claims. [0128]

Claims (20)

What claimed is:
1. A nanoemulsion comprising metabolite of ginseng saponin as an effective component, wherein said metabolite of ginseng saponin is obtained by conversion of glucose from ginseng saponin.
2. The nanoemulsion according to claim 1, wherein said metabolite of ginseng saponin is selected from the group consisting of 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol represented by the following formula 1; 20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol represented by the following formula 2; and 20-O-[α-L-arabinopyranosyl(1→6)-β-D-glucopyranosyl]-20(S)-protopanaxadiol represented by the following formula 3; and admixture thereof:
3.
Figure US20030175315A1-20030918-C00004
(wherein, R1 is O-Glc, R2 is OH and R3 is H).
Figure US20030175315A1-20030918-C00005
(wherein, R1 is O-Glc, R2 is OH and R3 is OH).
Figure US20030175315A1-20030918-C00006
(wherein, R1 is O-Glc6-1Arap, R2 is OH and R3 is H).
3. The nanoemulsion according to claim 2, wherein said admixture comprises 30˜50 wt % of 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, 5˜25 wt % of 20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol and 5˜25 wt % of 20-O-[α-L-arabinopyranosyl(1→6)-β-D-glucopyranosyl]-20(S)-protopanaxadiol as main components.
4. The nanoemulsion according to claim 1, which comprises said metabolite of ginseng saponin in an amount of 10−10˜50% by weight based on the total weight of nanoemulsion.
5. The nanoemulsion according to claim 4, which comprises said metabolite of ginseng saponin in an amount of 0.001˜30% by weight based on the total weight of nanoemulsion.
6. The nanoemulsion according to claim 1, which has the diameter of 30˜500 nm.
7. The nanoemulsion according to claim 1, which is emulsified with lecithin or its derivatives.
8. The nanoemulsion according to claim 7, wherein said lecithin is a liposome containing at lease one selected from the group consisting of unsaturated choline compound, serine compound, cephalin compound and hydrogenated compounds thereof, and is employed in an amount of 0.5˜10% by weight based on the total weight of nanoemulsion.
9. The nanoemulsion according to claims 8, wherein said unsaturated choline compound is phosphatidylcholine or lysophosphatidylcholine; and said cephalin compound is phosphatidylethanolamine.
10. The nanoemulsion according to any one of claims 7, wherein at least one supplementary emulsifier selected from the group consisting of anionic, cationic, nonionic and amphoteric emulsifier is employed together with lecithin, in a ratio of 0.5˜5 times based on the weight of lecithin.
11. The nanoemulsion according to claim 1, which is emulsified by nano-emulsification of homogenization under 500˜2,500 bar.
12. A method for preparing the nanoemulsion according to claim 1, which comprises a step of emulsifying said metabolite of ginseng saponin with lecithin or its derivatives.
13. The method according to claim 12, which comprises a step of emulsifying said metabolite of ginseng saponin by nano-emulsification.
14. The method according to claim 13, wherein said nano-emulsification is homogenization under 500˜2,500 bar.
15. A skin-care composition for anti-aging containing a nanoemulsion that comprises metabolite of ginseng saponin as an effective component in an amount of 10−8˜50% by weight based on the total weight of composition, wherein said metabolite of ginseng saponin is obtained by conversion of glucose from ginseng saponin.
16. The skin-care composition according to claim 15, wherein said metabolite of ginseng saponin is selected from the group consisting of 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol represented by the following formula 1; 20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol represented by the following formula 2; and 20-O-[α-L-arabinopyranosyl(1→6)-β-D-glucopyranosyl]-20(S)-protopanaxadiol represented by the following formula 3; and admixture thereof:
Figure US20030175315A1-20030918-C00007
(wherein, R1 is O-Glc, R2 is OH and R3 is H).
Figure US20030175315A1-20030918-C00008
(wherein, R1 is O-Glc, R2 is OH and R3 is OH).
Figure US20030175315A1-20030918-C00009
(wherein, R1 is O-Glc6-1Arap, R2 is OH and R3 is H).
17. The skin-care composition according to claim 16, wherein said admixture comprises 30˜50 wt % of 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, 5˜25 wt % of 20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol and 5˜25 wt % of 20-O-[α-L-arabinopyranosyl(1→6)-β-D-glucopyranosyl]-20(S)-protopanaxadiol as main components.
18. The skin-care composition according to claim 15, wherein said nanoemulsion comprises said metabolite of ginseng saponin in an amount of 10−10˜50% by weight based on the total weight of nanoemulsion.
19. The skin-care composition according to claim 15, wherein said nanoemulsion has the diameter of 30˜500 nm.
20. The composition according to claim 15, which has a formulation selected from the group consisting of skin softeners, astringents, nutrient toilet water, nutrient creams, massage creams, essences, eye creams, eye essences, cleansing creams, cleansing foams, cleansing water, packs, powders, body lotions, body creams, body oils, body essences, make-up bases, foundation, hairdyes, shampoos, rinses, body cleansers, toothpastes, oral cleaning fluid, lotions, ointments, gels, creams, patches and sprays.
US10/336,024 2002-01-05 2003-01-03 Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same Abandoned US20030175315A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
KR20020000614A KR100465977B1 (en) 2002-01-05 2002-01-05 Nanoemulsion having Compound K by nano-emulsion technology, and skin care and pharmaceutical compositions for external applications utilizing thereof
KR2002-614 2002-01-05
KR2002-613 2002-01-05
KR20020000613A KR100465976B1 (en) 2002-01-05 2002-01-05 Nanoemulsion having Ginsenoside F1 by nano-emulsion technology, and skin care and pharmaceutical compositions for external applications utilizing thereof
KR20020019032A KR100835863B1 (en) 2002-04-08 2002-04-08 Nanoemulsion having 20-O-[?-L-arabinopyranosyl1-?6-?-D-glucopyranosyl]-20S-protopanaxadiol by nano-emulsion technology, and skin care and pharmaceutical compositions for external applications utilizing thereof
KR2002-19032 2002-04-08
KR1020020029179A KR100835864B1 (en) 2002-05-27 2002-05-27 Nanoemulsion comprising metabolites of ginseng saponin as effective component and preparation method, and skin care compositions for antiaging agent utilizing thereof
KR2002-29179 2002-05-27

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US11/443,271 US8263565B2 (en) 2002-01-05 2006-05-31 Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/443,271 Division US8263565B2 (en) 2002-01-05 2006-05-31 Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same

Publications (1)

Publication Number Publication Date
US20030175315A1 true US20030175315A1 (en) 2003-09-18

Family

ID=27483543

Family Applications (2)

Application Number Title Priority Date Filing Date
US10/336,024 Abandoned US20030175315A1 (en) 2002-01-05 2003-01-03 Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same
US11/443,271 Active 2026-02-12 US8263565B2 (en) 2002-01-05 2006-05-31 Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same

Family Applications After (1)

Application Number Title Priority Date Filing Date
US11/443,271 Active 2026-02-12 US8263565B2 (en) 2002-01-05 2006-05-31 Nanoemulsion comprising metabolites of ginseng saponin as an active component and a method for preparing the same, and a skin-care composition for anti-aging containing the same

Country Status (3)

Country Link
US (2) US20030175315A1 (en)
EP (1) EP1327434B1 (en)
JP (1) JP4549625B2 (en)

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080031907A1 (en) * 2002-10-25 2008-02-07 Foamix Ltd. Cosmetic and pharmaceutical foam
US20080045467A1 (en) * 2004-01-26 2008-02-21 Amorepacific Corporation Composition Containing Ginsenoside F1 Or Compound K For Skin External Application
WO2009057836A1 (en) * 2007-10-31 2009-05-07 Amorepacific Corporation Use of melanin biosynthesis inhibitors from korean ginseng and the cosmetic composition containing thereof for skin whitening
US20100291244A1 (en) * 2009-05-14 2010-11-18 Il Hwa Co., Ltd. Methods for preparing a fermented ginseng concentrate or powder
US8114385B2 (en) 2003-08-04 2012-02-14 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US8119109B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Foamable compositions, kits and methods for hyperhidrosis
US8119106B2 (en) 2003-04-28 2012-02-21 Foamix Ltd Foamable iodine compositions
US8119150B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Non-flammable insecticide composition and uses thereof
US8343945B2 (en) 2007-12-07 2013-01-01 Foamix Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US8362091B2 (en) 2003-08-04 2013-01-29 Foamix Ltd. Foamable vehicle and pharmaceutical compositions thereof
US8435498B2 (en) 2002-10-25 2013-05-07 Foamix Ltd. Penetrating pharmaceutical foam
US8486374B2 (en) 2003-08-04 2013-07-16 Foamix Ltd. Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses
US8486376B2 (en) 2002-10-25 2013-07-16 Foamix Ltd. Moisturizing foam containing lanolin
US8512718B2 (en) 2000-07-03 2013-08-20 Foamix Ltd. Pharmaceutical composition for topical application
US8518376B2 (en) 2007-12-07 2013-08-27 Foamix Ltd. Oil-based foamable carriers and formulations
US20130243712A1 (en) * 2010-11-30 2013-09-19 Amorepacific Corporation Cosmetic composition for whitening and improving the resilience of skin
WO2013141565A1 (en) * 2012-03-20 2013-09-26 (주)아모레퍼시픽 Composition for enhancing defenses of skin
US8574639B2 (en) 2010-08-17 2013-11-05 ILHWA Co., Ltd. Fermented ginseng concentrate having IH-901
US8618081B2 (en) 2009-10-02 2013-12-31 Foamix Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US8636982B2 (en) 2007-08-07 2014-01-28 Foamix Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US8709385B2 (en) 2008-01-14 2014-04-29 Foamix Ltd. Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses
US8722021B2 (en) 2002-10-25 2014-05-13 Foamix Ltd. Foamable carriers
US8760906B2 (en) 2009-11-24 2014-06-24 Micron Technology, Inc. Techniques for reducing disturbance in a semiconductor memory device
US8795635B2 (en) 2006-11-14 2014-08-05 Foamix Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US8795693B2 (en) 2003-08-04 2014-08-05 Foamix Ltd. Compositions with modulating agents
US8900554B2 (en) 2002-10-25 2014-12-02 Foamix Pharmaceuticals Ltd. Foamable composition and uses thereof
US20150126463A1 (en) * 2013-11-04 2015-05-07 Hong Kong Baptist University Use of herbal saponins to regulate gut microflora
US9072667B2 (en) 2009-07-29 2015-07-07 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US9167813B2 (en) 2009-07-29 2015-10-27 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
US9265725B2 (en) 2002-10-25 2016-02-23 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9320705B2 (en) 2002-10-25 2016-04-26 Foamix Pharmaceuticals Ltd. Sensation modifying topical composition foam
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US9539208B2 (en) 2002-10-25 2017-01-10 Foamix Pharmaceuticals Ltd. Foam prepared from nanoemulsions and uses
US9622947B2 (en) 2002-10-25 2017-04-18 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US9668972B2 (en) 2002-10-25 2017-06-06 Foamix Pharmaceuticals Ltd. Nonsteroidal immunomodulating kit and composition and uses thereof
US9849142B2 (en) 2009-10-02 2017-12-26 Foamix Pharmaceuticals Ltd. Methods for accelerated return of skin integrity and for the treatment of impetigo
US9884017B2 (en) 2009-04-28 2018-02-06 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100835864B1 (en) 2002-05-27 2008-06-09 (주)아모레퍼시픽 Nanoemulsion comprising metabolites of ginseng saponin as effective component and preparation method, and skin care compositions for antiaging agent utilizing thereof
HU0202032A2 (en) * 2002-06-19 2004-10-28 D. Endre Radics Entering bioactive substances in Nanoemulziós formulation of the human body through the oral mucosa, mechanical pumpájú by spray.
KR100485326B1 (en) 2002-12-26 2005-04-27 주식회사 태평양 Promoter for the production of hyaluronic acid containing ginsenoside compound K
KR100820072B1 (en) * 2002-12-28 2008-04-10 (주)아모레퍼시픽 Control agent of Bcl-2 expression being Ginsenoside F1 as active component
CN100586444C (en) * 2003-09-30 2010-02-03 涌永制药株式会社 Method of processing ginseng for medicinal use and composition
KR100868905B1 (en) * 2004-03-26 2008-11-14 (주)아모레퍼시픽 Composition for preventing UVB-induced skin damage by treating both Gensenoside F1 and EGCG
KR100896697B1 (en) * 2004-04-09 2009-05-14 (주)아모레퍼시픽 Percutaneous absorption enhancing method of Rheum coreanum by high pressure-emulsion technology, and skin care and pharmaceutical compositions with whitening effect for external applications utilizing thereof
EP1773298A1 (en) * 2004-08-06 2007-04-18 Biospectrum, Inc. Multiple layered liposome and preparation method thereof
JP4693623B2 (en) * 2005-03-07 2011-06-01 共栄化学工業株式会社 Cosmetics
DE102006005767A1 (en) * 2006-02-07 2007-08-09 Henkel Kgaa Oxidative hair treatment agent with ginseng extract
KR100842070B1 (en) 2007-04-09 2008-06-30 박준원 Nano platinum ginsenoside particle and production method thereof
KR20080105470A (en) * 2007-05-31 2008-12-04 (주)아모레퍼시픽 Food composition containing ginseng fruit extract for preventing and improving obesity
PL2020221T3 (en) * 2007-06-19 2012-07-31 DMS (Derma Membrane Structure) in foaming creams
WO2010134650A1 (en) * 2009-05-19 2010-11-25 Il Hwa Co., Ltd. Methods for preparing a fermented ginseng concentrate or powder
JP2015082970A (en) * 2012-02-02 2015-04-30 星野科学株式会社 Method for producing panax ginseng effective ingredient
CN103381142B (en) * 2012-05-04 2016-12-14 上海现代药物制剂工程研究中心有限公司 One kind of ginsenoside Rh <sub> 1 </ sub> from the microemulsion composition and preparation method and use
KR101409761B1 (en) * 2012-06-20 2014-06-19 주식회사한국야쿠르트 A method of preparation for fermented red ginseng using conversion by enzyme mixture and fermentation by lactic acid bacterium and the products containing fermented red ginseng manufactured thereof as effective factor
WO2014101941A1 (en) * 2012-12-27 2014-07-03 Jean-Claude Epiphani Method for manufacturing an oil-in-water emulsion from an oily active substance, for cosmetic, food, or pharmaceutical use
KR20140131026A (en) * 2013-05-03 2014-11-12 (주)아모레퍼시픽 Skin external composition containing ginsenoside Y
JPWO2014203362A1 (en) * 2013-06-19 2017-02-23 金氏高麗人参株式会社 Ginsenoside composition
KR101512190B1 (en) * 2014-10-30 2015-05-04 주식회사 라비오뜨 Amiderm composition for transdermal transfer
CN105032282A (en) * 2015-06-24 2015-11-11 陈琳仁 Preparation method for high-purity gleditsia sinensis natural surfactant
KR101777920B1 (en) 2015-07-27 2017-09-14 재단법인 지능형 바이오 시스템 설계 및 합성 연구단 The composition containing ginsenoside F1 for removing amyloid plaques

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5576016A (en) * 1993-05-18 1996-11-19 Pharmos Corporation Solid fat nanoemulsions as drug delivery vehicles
US5919770A (en) * 1996-02-22 1999-07-06 Il Hwa Co., Ltd. Metabolites of ginseng saponins by human intestinal bacteria and its preparation for an anticancer

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5166139A (en) 1987-02-26 1992-11-24 Indena, S.P.A. Complexes of saponins and their aglycons with phospholipids and pharmaceutical and cosmetic compositions containing them
IT1203515B (en) 1987-02-26 1989-02-15 Indena Spa Complexes of saponins with phospholipids and pharmaceutical and cosmetic compositions containing them
JPH0532522A (en) * 1991-07-29 1993-02-09 Q P Corp Production of cosmetic and additive for cosmetic
IL101387A (en) 1992-03-26 1999-11-30 Pharmos Ltd Emulsion with enhanced topical and/or transdermal systemic effect utilizing submicron oil droplets
FR2695561B1 (en) * 1992-09-17 1994-12-02 Lvmh Rech Gie Cosmetic or dermatological composition containing at least one saponin ginsenoside type and its applications, including hair care.
FR2725369B1 (en) * 1994-10-07 1997-01-03 Oreal Cosmetic or dermatological composition consisting of an oil in water emulsion based on oily globules provided with a lamellar liquid crystal coating
JPH09176017A (en) * 1995-12-27 1997-07-08 Happy World:Kk Carcinostatic
CN1452629A (en) * 2000-05-31 2003-10-29 科学技术振兴事业团 Skin tissue regeneration prmoters comprising ginsenoside Rb1

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5576016A (en) * 1993-05-18 1996-11-19 Pharmos Corporation Solid fat nanoemulsions as drug delivery vehicles
US5919770A (en) * 1996-02-22 1999-07-06 Il Hwa Co., Ltd. Metabolites of ginseng saponins by human intestinal bacteria and its preparation for an anticancer

Cited By (76)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8512718B2 (en) 2000-07-03 2013-08-20 Foamix Ltd. Pharmaceutical composition for topical application
US8722021B2 (en) 2002-10-25 2014-05-13 Foamix Ltd. Foamable carriers
US8840869B2 (en) 2002-10-25 2014-09-23 Foamix Ltd. Body cavity foams
US10117812B2 (en) 2002-10-25 2018-11-06 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US9492412B2 (en) 2002-10-25 2016-11-15 Foamix Pharmaceuticals Ltd. Penetrating pharmaceutical foam
US9265725B2 (en) 2002-10-25 2016-02-23 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US8119109B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Foamable compositions, kits and methods for hyperhidrosis
US9539208B2 (en) 2002-10-25 2017-01-10 Foamix Pharmaceuticals Ltd. Foam prepared from nanoemulsions and uses
US8119150B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Non-flammable insecticide composition and uses thereof
US20080031907A1 (en) * 2002-10-25 2008-02-07 Foamix Ltd. Cosmetic and pharmaceutical foam
US9668972B2 (en) 2002-10-25 2017-06-06 Foamix Pharmaceuticals Ltd. Nonsteroidal immunomodulating kit and composition and uses thereof
US8435498B2 (en) 2002-10-25 2013-05-07 Foamix Ltd. Penetrating pharmaceutical foam
US10322085B2 (en) 2002-10-25 2019-06-18 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9713643B2 (en) 2002-10-25 2017-07-25 Foamix Pharmaceuticals Ltd. Foamable carriers
US8486376B2 (en) 2002-10-25 2013-07-16 Foamix Ltd. Moisturizing foam containing lanolin
US9622947B2 (en) 2002-10-25 2017-04-18 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US8900554B2 (en) 2002-10-25 2014-12-02 Foamix Pharmaceuticals Ltd. Foamable composition and uses thereof
US9320705B2 (en) 2002-10-25 2016-04-26 Foamix Pharmaceuticals Ltd. Sensation modifying topical composition foam
US8741265B2 (en) 2002-10-25 2014-06-03 Foamix Ltd. Penetrating pharmaceutical foam
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
US8486375B2 (en) 2003-04-28 2013-07-16 Foamix Ltd. Foamable compositions
US8119106B2 (en) 2003-04-28 2012-02-21 Foamix Ltd Foamable iodine compositions
US8486374B2 (en) 2003-08-04 2013-07-16 Foamix Ltd. Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses
US8362091B2 (en) 2003-08-04 2013-01-29 Foamix Ltd. Foamable vehicle and pharmaceutical compositions thereof
US9050253B2 (en) 2003-08-04 2015-06-09 Foamix Pharmaceuticals Ltd. Oleaginous pharmaceutical and cosmetic foam
US8795693B2 (en) 2003-08-04 2014-08-05 Foamix Ltd. Compositions with modulating agents
US8703105B2 (en) 2003-08-04 2014-04-22 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US9101662B2 (en) 2003-08-04 2015-08-11 Foamix Pharmaceuticals Ltd. Compositions with modulating agents
US9636405B2 (en) 2003-08-04 2017-05-02 Foamix Pharmaceuticals Ltd. Foamable vehicle and pharmaceutical compositions thereof
US8518378B2 (en) 2003-08-04 2013-08-27 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US8114385B2 (en) 2003-08-04 2012-02-14 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US20080045467A1 (en) * 2004-01-26 2008-02-21 Amorepacific Corporation Composition Containing Ginsenoside F1 Or Compound K For Skin External Application
US9682021B2 (en) 2006-11-14 2017-06-20 Foamix Pharmaceuticals Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US8795635B2 (en) 2006-11-14 2014-08-05 Foamix Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US9662298B2 (en) 2007-08-07 2017-05-30 Foamix Pharmaceuticals Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US8636982B2 (en) 2007-08-07 2014-01-28 Foamix Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
WO2009057836A1 (en) * 2007-10-31 2009-05-07 Amorepacific Corporation Use of melanin biosynthesis inhibitors from korean ginseng and the cosmetic composition containing thereof for skin whitening
US8647610B2 (en) 2007-10-31 2014-02-11 Amorepacific Corporation Use of melanin biosynthesis inhibitors from korean ginseng and the cosmetic composition containing thereof for skin whitening
US20100310485A1 (en) * 2007-10-31 2010-12-09 Jun Seong Park Use of melanin biosynthesis inhibitors from korean ginseng and the cosmetic composition containing thereof for skin whitening
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US9549898B2 (en) 2007-12-07 2017-01-24 Foamix Pharmaceuticals Ltd. Oil and liquid silicone foamable carriers and formulations
US8900553B2 (en) 2007-12-07 2014-12-02 Foamix Pharmaceuticals Ltd. Oil and liquid silicone foamable carriers and formulations
US9795564B2 (en) 2007-12-07 2017-10-24 Foamix Pharmaceuticals Ltd. Oil-based foamable carriers and formulations
US9161916B2 (en) 2007-12-07 2015-10-20 Foamix Pharmaceuticals Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US8343945B2 (en) 2007-12-07 2013-01-01 Foamix Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US8518376B2 (en) 2007-12-07 2013-08-27 Foamix Ltd. Oil-based foamable carriers and formulations
US8709385B2 (en) 2008-01-14 2014-04-29 Foamix Ltd. Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses
US10213384B2 (en) 2009-04-28 2019-02-26 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US9884017B2 (en) 2009-04-28 2018-02-06 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US20100291244A1 (en) * 2009-05-14 2010-11-18 Il Hwa Co., Ltd. Methods for preparing a fermented ginseng concentrate or powder
US8541035B2 (en) * 2009-05-14 2013-09-24 Il Hwa Co., Ltd. Methods for preparing a fermented ginseng concentrate or powder
US9167813B2 (en) 2009-07-29 2015-10-27 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US10092588B2 (en) 2009-07-29 2018-10-09 Foamix Pharmaceuticals Ltd. Foamable compositions, breakable foams and their uses
US9572775B2 (en) 2009-07-29 2017-02-21 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US9072667B2 (en) 2009-07-29 2015-07-07 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US10238746B2 (en) 2009-10-02 2019-03-26 Foamix Pharmaceuticals Ltd Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US8618081B2 (en) 2009-10-02 2013-12-31 Foamix Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US9675700B2 (en) 2009-10-02 2017-06-13 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US8871184B2 (en) 2009-10-02 2014-10-28 Foamix Ltd. Topical tetracycline compositions
US10322186B2 (en) 2009-10-02 2019-06-18 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10137200B2 (en) 2009-10-02 2018-11-27 Foamix Pharmaceuticals Ltd. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US8945516B2 (en) 2009-10-02 2015-02-03 Foamix Pharmaceuticals Ltd. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US8865139B1 (en) 2009-10-02 2014-10-21 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US9849142B2 (en) 2009-10-02 2017-12-26 Foamix Pharmaceuticals Ltd. Methods for accelerated return of skin integrity and for the treatment of impetigo
US10213512B2 (en) 2009-10-02 2019-02-26 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10029013B2 (en) 2009-10-02 2018-07-24 Foamix Pharmaceuticals Ltd. Surfactant-free, water-free formable composition and breakable foams and their uses
US10265404B2 (en) 2009-10-02 2019-04-23 Foamix Pharmaceuticals Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US8992896B2 (en) 2009-10-02 2015-03-31 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10086080B2 (en) 2009-10-02 2018-10-02 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US9812179B2 (en) 2009-11-24 2017-11-07 Ovonyx Memory Technology, Llc Techniques for reducing disturbance in a semiconductor memory device
US8760906B2 (en) 2009-11-24 2014-06-24 Micron Technology, Inc. Techniques for reducing disturbance in a semiconductor memory device
US8574639B2 (en) 2010-08-17 2013-11-05 ILHWA Co., Ltd. Fermented ginseng concentrate having IH-901
US20130243712A1 (en) * 2010-11-30 2013-09-19 Amorepacific Corporation Cosmetic composition for whitening and improving the resilience of skin
US9770404B2 (en) * 2010-11-30 2017-09-26 Amorepacific Corporation Cosmetic composition for whitening and improving the resilience of skin
WO2013141565A1 (en) * 2012-03-20 2013-09-26 (주)아모레퍼시픽 Composition for enhancing defenses of skin
US20150126463A1 (en) * 2013-11-04 2015-05-07 Hong Kong Baptist University Use of herbal saponins to regulate gut microflora

Also Published As

Publication number Publication date
EP1327434A1 (en) 2003-07-16
US20060216261A1 (en) 2006-09-28
JP2003212776A (en) 2003-07-30
JP4549625B2 (en) 2010-09-22
US8263565B2 (en) 2012-09-11
EP1327434B1 (en) 2008-08-13

Similar Documents

Publication Publication Date Title
JP3958968B2 (en) External preparation for skin and whitening agents
KR100554860B1 (en) Skin-lightening cosmetic
KR101217382B1 (en) EXTERNAL DERMATOLOGICAL FORMULATION COMPRISING SACCHARIDE DERIVATIVE OF α,α-TREHALOSE
DE60310731T2 (en) New molecules of noraporphin derived
AU2005204685B2 (en) Cosmetic composition and method for retarding hair growth
CN105585601B (en) Anti-aging composition for external use, and a method for producing skin
Nokhodchi et al. The effect of terpene concentrations on the skin penetration of diclofenac sodium
DE60031836T2 (en) Skin care preparation mediated intercellular communication
KR100970544B1 (en) Composition for preparation for external use on skin and method of using the same
KR101338546B1 (en) Agent for external application to the skin
US20020098213A1 (en) Use of ellagic acid and its derivatives in cosmetics and dermatology
US7807625B2 (en) Anti-wrinkle composition
JP3818674B2 (en) External preparation for skin
DE60306565T2 (en) Compositions for topical use against cancer
JP2711549B2 (en) Gray hair prevention and composition for improving
HUT71381A (en) Cosmetic composition for the simultaneous treatment of the surface and deep layers of the skin, its use
EP0978274B1 (en) Emulsifier and emulsified composition
KR20010057585A (en) External preparation for skin
KR101537834B1 (en) Cosmetic compositions comprising exopolysaccharides derived from microbial mats
EP1648403B1 (en) Slimming cosmetic composition comprising cafestol or kahweol
KR101140039B1 (en) A composition that contains ginsenoside F1 and/or Compound K for skin external application
JP4549625B2 (en) Fine emulsified particles and a manufacturing method thereof and ginseng saponin metabolite of the active ingredient, as well as cosmetic composition for preventing skin aging containing the same
DE69937679T2 (en) Water-soluble composition containing active ingredients for skin depigmentation
EP1039878A1 (en) Cosmetic composition containing at least one auxin and its use
CN1289053C (en) Cosmetics composition

Legal Events

Date Code Title Description
AS Assignment

Owner name: PACIFIC CORPORATION, KOREA, REPUBLIC OF

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:YOO, BYUNG HEE;KANG, BYUNG YOUNG;YEOM, MYEONG HOON;AND OTHERS;REEL/FRAME:013833/0830

Effective date: 20021213

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION