WO2009082185A1 - Skin-whitening agent containing platycodin d - Google Patents

Skin-whitening agent containing platycodin d Download PDF

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Publication number
WO2009082185A1
WO2009082185A1 PCT/KR2009/000374 KR2009000374W WO2009082185A1 WO 2009082185 A1 WO2009082185 A1 WO 2009082185A1 KR 2009000374 W KR2009000374 W KR 2009000374W WO 2009082185 A1 WO2009082185 A1 WO 2009082185A1
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WO
WIPO (PCT)
Prior art keywords
skin
composition
present
platicodin
whitening
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PCT/KR2009/000374
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French (fr)
Korean (ko)
Inventor
Yeong-Sik Kim
Deok-Hoon Park
Eun-Sun Jung
Jong-Sung Lee
Original Assignee
Biospectrum, Inc.
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Application filed by Biospectrum, Inc. filed Critical Biospectrum, Inc.
Priority to JP2010545805A priority Critical patent/JP2011511063A/en
Priority to CN200980100941XA priority patent/CN101854909B/en
Priority to PCT/KR2009/000374 priority patent/WO2009082185A1/en
Publication of WO2009082185A1 publication Critical patent/WO2009082185A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to a composition for skin whitening, and more particularly, skin whitening including platicodine-D, which has excellent product stability, can be safely used without side effects on the skin, and inhibits melanin production and has excellent pigmentation inhibitory effect.
  • Human skin color is determined by the concentration and distribution of melanin in the skin. In addition to genetic factors, it is also influenced by environmental or physiological conditions such as sun ultraviolet rays, fatigue and stress.
  • Melanin pigment produced by melanocytes of human skin is a phenolic polymer having a complex form of black pigment and protein, and plays an important role in preventing skin damage caused by ultraviolet rays. In melanin biosynthesis, the action of tyrosinase in melanocytes is reported to be the most important. Tyrosinase plays a key role in the skin blackening process by converting tyrosine, an amino acid, into dopa and dopaquinone, intermediates of melanin polymer production. However, although the pathway by which melanin is made is known, it is still not clear what mechanisms induce melanin synthesis, the previous step in which tyrosinase works.
  • substances having inhibitory activity against tyrosinase such as hydroquinone, ascorbic acid, kojic acid, and glutathione are used to prevent skin whitening or hyperpigmentation.
  • hydroquinone exhibits a predetermined whitening effect but severe skin irritation has a problem of limiting the blending amount to a very small amount.
  • Ascorbic acid is easily oxidized, and the cosmetics containing it are discolored and discolored. Acid is unstable in solution, which complicates the manufacturing process of cosmetics.
  • thiol-based compounds such as glutathione and cysteine not only have a characteristic unpleasant odor, but also have problems with transdermal absorption, and glycosides and derivatives thereof have high polarity, making it difficult to use as a cosmetic ingredient.
  • vitamin C has a problem in that it is easily oxidized in the aqueous solution state does not have a continuous effect. Accordingly, in recent years, compositions for skin whitening including natural herbal extracts have been developed, but most of them have color problems, and there is a problem in formulation, and the active ingredients have not been identified, and thus there is a problem in that the same effect cannot be expected when manufacturing products.
  • Platycodin-D is one of the triterpenoid saponin compounds present in the roots of bellflower, and has been reported to have anti-inflammatory, anti-obesity, cholesterol-lowering effects, and analgesic inhibitory effects.
  • US Patent Application No. 2002/0197334 discloses that platicodine-di has an effect on diabetes, and WO 2005/007181 discloses that it has an effect of inhibiting cancer through a mechanism of inhibiting neovascular production. Doing. As such, various studies on the efficacy of the natural substance platicodine-D have been made.
  • One object of the present invention relates to a cosmetic composition for skin whitening comprising platicodine-di.
  • Another object of the present invention relates to a pharmaceutical composition for skin whitening comprising platicodine-di.
  • Another object of the present invention relates to a method for whitening skin by applying the composition to the skin of a mammal, including humans.
  • platicodine-D has a higher inhibitory effect on intracellular tyrosinase and a melanin production inhibitory effect than vitamin C, which is a main component of the existing whitening agent.
  • vitamin C which is a main component of the existing whitening agent.
  • the present invention relates to a cosmetic composition for skin whitening comprising Platycodin D.
  • Platycodin-D (platycodin-D) of the present invention is a kind of triterpenoid saponin derived from plants having the structure of the following formula (1).
  • Platicodin-di of the present invention may be prepared from chemical modifications, or by chemical modification of triterpenoid saponins isolated from natural sources (eg, bellflower, etc.), or obtained from natural sources. Or a commercially prepared product (eg, Platycodin D from Pharmavan).
  • the platicodine-di of the present invention can be extracted and separated at 0 ° C. to 50 ° C. using a solvent such as water, alcohol or acetone at the root of bellflower, and such extraction and separation methods are available to those skilled in the art. It is well known.
  • the platicodine-D of the present invention In order to examine the whitening effect of the platicodine-D of the present invention, compared with vitamin C (vitamin C), which is used as a conventional whitening cosmetic raw material, intracellular tyrosinase activity and melanin production inhibitory effect generally used for screening whitening substances As a result, at the same concentration, the platycodine-diga of the present invention was superior to the inhibitory effect of tyrosinase activity and melanogenesis by about 10% or more than vitamin C. Therefore, the platicodine-di of the present invention is excellent in the whitening effect.
  • vitamin C vitamin C
  • Platicodin-D of the formula (1) of the present invention derivatives exhibiting a skin whitening effect by inhibiting melanin production and / or tyrosinase activity of the derivatives obtained by the addition or substitution reaction of substituents commonly practiced in the art It is clear to those skilled in the art in consideration of the level of skill in the art.
  • the amount of platicodine-di in the cosmetic composition for skin whitening of the present invention is preferably 0.001 to 10% by weight, preferably 0.001 to 5% by weight based on the total composition. If it is less than 0.001% by weight, the whitening effect is too weak, and if it exceeds 15% by weight, there is a problem that the increase in effect due to the increase of the content is insufficient and the stability of the formulation is not secured.
  • the cosmetic composition for skin whitening of the present invention may include components conventionally used in cosmetic compositions in addition to Platicodin-D as an active ingredient.
  • components conventionally used in cosmetic compositions in addition to Platicodin-D as an active ingredient.
  • auxiliaries and / or carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavorings.
  • the cosmetic composition may further include a skin absorption promoting material to enhance the skin whitening effect.
  • Cosmetic compositions of the present invention can be prepared in any formulation conventionally prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are not limited thereto. More preferably, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.
  • the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide
  • cellulose derivatives polyethylene glycols
  • silicones bentonites
  • silicas talc or zinc oxide
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
  • a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.
  • liquid carrier diluents such as water, ethanol or propylene glycol
  • suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
  • the carrier component is aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide.
  • Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
  • the present invention relates to a pharmaceutical composition for skin whitening comprising Platycodin D.
  • the amount of platicodine-di may comprise 0.001 to 10% by weight, preferably 0.001 to 5% by weight based on the total composition.
  • the pharmaceutical composition may be formulated as a conventional agent in the pharmaceutical field according to the therapeutic purpose, for example, tablets, capsules, powders, granules, suspensions, emulsions, syrups, emulsions, warnings, ointments, sprays , Oils, gels, spirits, tinctures, baths, linings, lotions, patches, pads, creams and the like.
  • the topical skin preparation for topical administration directly applied to the affected area is in the form of an ointment, lotion, spray, gel or the like.
  • These dermal external preparations may also be included in support bases or matrices that may be applied directly to the treatment site, and examples of the support bases include gauze or bandages.
  • the pharmaceutical composition used in the formulation may be in colloidal form or dried powder form or the like.
  • the skin surface temperature, skin pH, transdermal water loss value, epidermal total lipid value, etc. should be considered.
  • oil-soluble substrates such as water-soluble substrates, emulsion bases, suspension bases, such as purified lanolin.
  • These ointments include antioxidants (e.g. tocopherol, BHA, BHT, NDGA, etc.), preservatives (e.g. phenolic substances, chlorobutanol, benzyl alcohol, parabens, benzoic acid, etc.), moisturizers (e.g.
  • Dissolution aids eg, ethanol, propylene glycol
  • softening aids eg, liquid paraffin, glycerin, propylene glycol, surfactants, etc.
  • a lotion When formulated into a lotion, it may be prepared in a lotion such as solution, suspension or emulsion type, and in the case of a lotion applied to the skin, for example, may be prepared to have a viscosity of 200 cps to 500 cps, and a soft feeling when applied. It is preferable to prepare a compound by combining a humectant such as glycerin and propylene glycol.
  • a propellant or the like When formulated with a spray, a propellant or the like may be combined with the additives to disperse the dispersed dispersion or wet powder.
  • absorption accelerators When formulated as a patch, absorption accelerators can be used to increase the absorption of the compound through the skin.
  • compositions of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
  • Formulations of the pharmaceutical compositions of the present invention include powders, granules, tablets, capsules, suspensions, emulsions, syrups, oral formulations such as aerosols, external preparations such as ointments, creams, suppositories, sterile injectable solutions, etc. It may be used in any form suitable for pharmaceutical formulations, including.
  • the pharmaceutical composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes such as parenteral, oral, and all modes of administration can be expected, for example, oral, It may be administered by rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection. At this time, as a parenteral route, transdermal administration is preferred, and topical application is most preferred.
  • the topical administration includes transdermal delivery resulting in systemic effects.
  • excipients e.g. lactose, starch, cellulose, lactose, polyethylene glycol, etc.
  • lubricants e.g. magnesium stearate, stearic acid, glyceryl behenate, talc, etc.
  • preservatives e.g. benzyl Alconium chloride, etc.
  • composition of the present invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat or prevent a disease at a reasonable benefit / risk ratio applicable to medical treatment or prophylaxis, and an effective dose level means the type of disease and its severity; Activity of the drug; The age, body weight, health and sex of the patient; Sensitivity to the drug of the patient; The time of administration, route of administration, and rate of excretion of the specific extract used; Duration of treatment; It may be determined according to factors including drugs used in combination or coincidental with the specific extract used and factors well known in the medical arts.
  • the oral dosage form may vary depending on the age, sex, and weight of the patient, but the amount of 0.1 to 100 mg / kg may be administered once to several times a day.
  • the present invention relates to a method for whitening skin by applying the cosmetic composition or pharmaceutical composition of the present invention to the skin of a mammal, including a human.
  • whitening refers to preventing or improving blackening of the skin caused by the deposition of melanin due to various causes such as aging, ultraviolet rays, contaminated environment, and the like.
  • the platicodine-D of the present invention is excellent in inhibiting tyrosinase activity and inhibiting melanin production by at least about 10% even when compared to vitamin C (vitamin C) conventionally used as a raw material for cosmetics for the purpose of skin whitening. It was. Therefore, Platicodine-D, which is included as an active ingredient in the cosmetic composition and the pharmaceutical composition of the present invention, has an excellent skin whitening effect, and thus the skin may be effectively whitened by applying the composition to the skin.
  • vitamin C vitamin C
  • the cumulative skin irritation test against platicodine-D was found to be a natural substance that is harmless to humans. Therefore, the platicodine-D of the present invention has little toxicity and side effects, so it can be used safely even in long-term use, and in particular, it can be safely applied to cosmetic compositions and pharmaceutical compositions as described above.
  • B16 melanoma cells were used to measure the inhibitory effect of melanin production by Platicodin-D (Sigma), and this was compared with the melanin production inhibitory effect of vitamin C, which is known to inhibit melanogenesis.
  • This experiment was performed using murine melanoma (B-16 F10) cells in DMEM medium containing 10% fetal bovine serum (FBS) in 6-well plates at 1 ⁇ 10 per well. 5 After inoculation with dogs, 5% CO 2 And Cells were incubated at 37 ° C. until they were at least about 80% adhered to the bottom of the well. After incubation, remove the medium and replace Platicodin-D and vitamin C in a DMEM medium diluted to the appropriate concentration, 5% CO 2, Incubated at 37 ° C. for 3 days. The concentration range of Platicodin-D was determined to be 0.1 uM, 0.5 uM, 1 uM without cytotoxicity.
  • the concentration range of vitamin C was 0.1 uM, 0.5 uM, 1 uM in the same manner as Platicodin-D.
  • the medium was removed, and the collected cells were washed with PBS (phosphated buffer saline) and treated with trypsin to recover the cells.
  • the recovered cells were counted using a hematocytometer, centrifuged at 5,000 to 10,000 rpm for 10 minutes, and then the supernatant was removed to obtain pellets.
  • the cell pellet was dried at 60 ° C., and 100 ⁇ l of 1 M sodium hydroxide solution containing 10% DMSO was added to obtain intracellular melanin in a 60 ° C. thermostat. Using this solution, the absorbance at 490 nm was measured with a microplate reader to determine the amount of melanin per cell. The results are shown in Table 1 below.
  • Rat pigment cells (B16 melanoma cells) were used to measure the inhibitory effect of melanin production by placodin-di and compared with the inhibitory effect of intracellular tyrosinase activity by vitamin C, which is known to inhibit melanin production.
  • murine melanoma (B-16 F1) cells were inoculated in DMEM medium containing 10% FBS (fetal bovine serum) at 1 ⁇ 10 5 per well in a 6-well plate, followed by 5% CO 2 at 37 ° C. The cells were cultured until at least 80% of the cells adhered to the well bottom. After incubation, the medium was removed and Platicodin-D and Vitamin C were replaced with DMEM medium diluted to appropriate concentrations and incubated at 5% CO 2, 37 ° C. for 3 days. The concentration ranges of platicodine-di and vitamin C were 0.1 uM, 0.5 uM, and 1 uM as in Example 1.
  • the medium was removed, and the collected cells were washed with PBS (phosphated buffer saline), which was treated with trypsin to recover the cells.
  • the recovered cells were counted using a hematocytometer, centrifuged at 5,000 to 10,000 rpm for 10 minutes, and then the supernatant was removed to obtain pellets.
  • the cell pellet was pulverized using lysis buffer, and the supernatant was collected by centrifugation at 12,000 rpm for 10 minutes. Using this solution, the absorbance was measured at 492 nm using a microplate reader to determine the cell number tyrosinase activity. The results are shown in Table 2 below.
  • platycodine-di showed better intracellular tyrosinase inhibition than vitamin C.
  • the aluminum foil was peeled off and a sample (platicodine-di and vitamin C) was applied in the following manner. Pigmentation appeared 2 or 3 days after the UV irradiation, and reached a peak after about 2 weeks, and each sample was applied therefrom.
  • the effect was determined by measuring the degree of black and white of the skin using a color difference meter (Minolta CR2002 chromameter), the results are shown in Table 3 below.
  • L * A * B * colorimeter is used to display color, and L * value was used as an index in this invention.
  • L * value was calibrated with a standard whiteboard, and L * value was measured 5 times or more at one site, and pigmentation was equalized.
  • the difference (L * ) between the skin color at the start of application and at the end of application was determined and the effect was judged by this value. Comparing the L * value for the sample application site and the control site and comparing the effect of the whitening material can be seen. The results are shown in Table 3 below.
  • Platicodin-D showed a better whitening effect than vitamin C, and cumulative irritation was not observed during the test application of the test substance, and thus safety was also excellent.
  • Skin external preparations containing Platicodin-di and vitamin C were prepared by the ingredient contents of Table 4 below.
  • the control group is an external skin preparation that does not include a tyrosinase inhibitor
  • test group 1 and test group 2 are external skin preparations including platicodine-D and vitamin C, respectively.
  • Control Test group 1 Test group 2 Purified water 72 72 72 glycerin 8.0 8.0 8.0 Butylene glycol 4.0 4.0 4.0 Platicodin-D 0 1.0 0 Vitamin c 0 0 1.0 Caprylic Capri Triglyceride 8.0 8.0 8.0 Squalane 5.0 5.0 5.0 Cetearyl Glucoside 1.5 1.5 1.5 Sorbitan stearate 0.4 0.4 0.4 Cetearyl Alcohol 1.0 1.0 1.0 1.0 Trimethanolamine 0.1 0.1 0.1 Gross weight 100 100 100 100 100 100 100 100
  • Platicodine-D stimulates the skin by performing a total of nine 24-hour cumulative blisters on the upper forearm every other day in 30 healthy adults using each skin preparation prepared in Example 4-1. It was measured whether or not giving.
  • the patch method used the fin chamber (Finn chamber, Epitest Ltd, Finland). 15ul of each said skin external preparation was dripped at the chamber, and the patch was performed. The degree of response to the skin each time was scored using the following Experimental Formula 2, and the results are shown in Table 5 below.
  • Average responsiveness [[response index x responsiveness / total number of subjects x highest score (4 points)] x 100] ⁇ Number of tests (9 times)
  • the external skin preparations containing Platicodin-D did not show a distinct cumulative stimulation pattern as the external skin preparations containing the control or vitamin C and was determined to be a safe substance for human skin. .
  • Platicodin-D of the present invention has a higher inhibitory effect on intracellular tyrosinase and a melanin production inhibitory effect than vitamin C, which is a main component of the existing whitening agent.
  • vitamin C which is a main component of the existing whitening agent.

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Abstract

The present invention relates to cosmetic and pharmaceutical compositions which include platycodin D as an active ingredient. The platycodin D of the present invention can be used safely and without side effects on the skin, and also has outstanding effects in suppressing the production of melanin and impeding pigment deposition, and thus a composition which contains the present invention as an active ingredient can be used very effectively to improve skin patches and freckles and for skin whitening.

Description

플라티코딘-디를 함유하는 피부미백제Skin whitening agents containing placodin-di
본 발명은 피부미백용 조성물에 관한 것으로서, 보다 상세하게는 제품 안정성이 우수하고 피부에 대한 부작용 없이 안전하게 사용될 수 있으며 멜라닌 생성을 억제하여 색소 침착 저해 효과가 우수한 플라티코딘-디를 포함하는 피부미백용 화장료 및 약제학적 조성물에 관한 것이다.The present invention relates to a composition for skin whitening, and more particularly, skin whitening including platicodine-D, which has excellent product stability, can be safely used without side effects on the skin, and inhibits melanin production and has excellent pigmentation inhibitory effect. Cosmetics and pharmaceutical compositions for.
사람의 피부색은 피부 내부의 멜라닌(melanin) 농도와 분포에 따라 결정되는데, 유전적인 요인 외에도 태양 자외선이나 피로, 스트레스 등의 환경적 또는 생리적 조건에 의해서도 영향을 받는다. 인체 피부의 멜라닌 세포에서 생성되는 멜라닌 색소는 검은 색소와 단백질의 복합형태를 갖는 페놀계 고분자 물질로서, 자외선으로 발생하는 피부손상을 차단하는 중요한 역할을 하고 있다. 멜라닌 생합성에는 멜라닌 세포에 존재하는 티로시나제의 작용이 가장 중요한 것으로 보고되어 있다. 티로시나제(tyrosinase)는 아미노산의 일종인 티로신(tyrosine)을 멜라닌 중합체 생성의 중간산물인 도파(DOPA), 도파퀴논(dopaquinone)으로 전환함으로써 피부 흑화과정에 핵심적 역할을 수행한다. 그러나, 멜라닌이 만들어지는 경로는 알려져 있지만, 티로시나제가 작용하는 이전 단계인 멜라닌 합성을 유도하는 메카니즘(mechanism)이 무엇인지에 대해서는 아직도 자세히 밝혀지지 않고 있다.Human skin color is determined by the concentration and distribution of melanin in the skin. In addition to genetic factors, it is also influenced by environmental or physiological conditions such as sun ultraviolet rays, fatigue and stress. Melanin pigment produced by melanocytes of human skin is a phenolic polymer having a complex form of black pigment and protein, and plays an important role in preventing skin damage caused by ultraviolet rays. In melanin biosynthesis, the action of tyrosinase in melanocytes is reported to be the most important. Tyrosinase plays a key role in the skin blackening process by converting tyrosine, an amino acid, into dopa and dopaquinone, intermediates of melanin polymer production. However, although the pathway by which melanin is made is known, it is still not clear what mechanisms induce melanin synthesis, the previous step in which tyrosinase works.
이와 같은 멜라닌의 합성이 피부 내에서 과도하게 일어나면, 피부 톤을 어둡게 하고, 기미, 주근깨 등을 발생시키기도 한다. 따라서, 피부내의 멜라닌 색소의 합성을 저해시키면, 피부 톤을 밝게 하여 피부 미백을 실현할 수 있을 뿐만 아니라 자외선, 호르몬 및 유전적 원인에 기인하여 발생하는 기미, 주근깨 등의 피부 과색소 침착증을 개선시킬 수 있다.When such synthesis of melanin occurs excessively in the skin, it may darken the skin tone and cause blemishes and freckles. Therefore, by inhibiting the synthesis of melanin pigment in the skin, not only can brighten the skin tone to realize skin whitening, but also improve skin hyperpigmentation such as spots, freckles, etc. caused by ultraviolet rays, hormones and genetic causes. have.
따라서, 종래에는 하이드로퀴논(hydroquinone)이나 아스콜빈산(ascorbic acid), 코지산(kojic acid), 글루타티온(glutathione)과 같은 티로시나제에 대해 저해 활성을 갖는 물질이 사용하여 피부 미백이나 피부 과색소 침착증을 개선하였다. 그러나, 하이드로퀴논은 소정의 미백효과를 발휘하지만 피부자극성이 심하여 배합량을 극소량으로 제한해야 하는 문제점이 있고, 아스콜빈산은 산화되기 쉬워 이를 배합한 화장료는 변색, 변취되는 등의 문제가 발생하며, 코지산은 용액 내에서 불안전하여 화장료의 제조공정이 복잡해진다는 단점이 있다. 또한, 글루타티온, 시스테인 등의 티올계 화합물은 특유의 불쾌한 냄새를 가질 뿐만 아니라 경피흡수에도 문제점이 있고, 이들의 배당체 및 유도체들도 극성이 높으므로 화장료의 배합 성분으로 사용하기는 어렵다. 그 외에 비타민 C의 경우 수용액 상태에서 쉽게 산화되어 지속적인 효과를 내지 못하는 문제점이 있다. 이에 따라 최근에는 천연 생약 추출물들을 포함한 피부 미백용 조성물들이 개발되고 있지만, 대부분 색깔을 띄고 있어 배합상에서의 문제점이 있고, 유효성분이 동정되지 않았기 때문에 제품 제조시 동일 효과를 기대할 수 없는 문제점이 있다. Therefore, conventionally, substances having inhibitory activity against tyrosinase such as hydroquinone, ascorbic acid, kojic acid, and glutathione are used to prevent skin whitening or hyperpigmentation. Improved. However, hydroquinone exhibits a predetermined whitening effect but severe skin irritation has a problem of limiting the blending amount to a very small amount. Ascorbic acid is easily oxidized, and the cosmetics containing it are discolored and discolored. Acid is unstable in solution, which complicates the manufacturing process of cosmetics. In addition, thiol-based compounds such as glutathione and cysteine not only have a characteristic unpleasant odor, but also have problems with transdermal absorption, and glycosides and derivatives thereof have high polarity, making it difficult to use as a cosmetic ingredient. In addition, vitamin C has a problem in that it is easily oxidized in the aqueous solution state does not have a continuous effect. Accordingly, in recent years, compositions for skin whitening including natural herbal extracts have been developed, but most of them have color problems, and there is a problem in formulation, and the active ingredients have not been identified, and thus there is a problem in that the same effect cannot be expected when manufacturing products.
한편, 플라티코딘-디(platycodin-D)는 도라지 뿌리에 존재하는 트리터펜 사포닌계(triterpenoid saponin) 화합물 중 하나로 항염효과, 항비만효과, 콜레스테롤 저하효과, 통각 억제효과가 있는 것으로 보고되고 있다. 또한 미국특허출원 제2002/0197334호에서는 플라티코딘-디가 당뇨병에 효과가 있음을 개시하고 있고 국제공개 WO 2005/007181에서는 신혈관 생성을 억제하는 기전을 통해 암을 억제하는 효과가 있음을 개시하고 있다. 이와 같이 천연 물질인 플라티코딘-디의 효능에 대한 다양한 연구가 이루어지고 있다.Platycodin-D is one of the triterpenoid saponin compounds present in the roots of bellflower, and has been reported to have anti-inflammatory, anti-obesity, cholesterol-lowering effects, and analgesic inhibitory effects. In addition, US Patent Application No. 2002/0197334 discloses that platicodine-di has an effect on diabetes, and WO 2005/007181 discloses that it has an effect of inhibiting cancer through a mechanism of inhibiting neovascular production. Doing. As such, various studies on the efficacy of the natural substance platicodine-D have been made.
본 발명의 하나의 목적은 플라티코딘-디를 포함하는 피부 미백용 화장료 조성물에 관한 것이다.One object of the present invention relates to a cosmetic composition for skin whitening comprising platicodine-di.
본 발명의 다른 하나의 목적은 플라티코딘-디를 포함하는 피부 미백용 약제학적 조성물에 관한 것이다.Another object of the present invention relates to a pharmaceutical composition for skin whitening comprising platicodine-di.
본 발명의 다른 하나의 목적은 상기 조성물을 인간을 포함한 포유동물의 피부에 도포하여 피부를 미백하는 방법에 관한 것이다.Another object of the present invention relates to a method for whitening skin by applying the composition to the skin of a mammal, including humans.
본 발명에 의하면 플라티코딘-디는 기존 미백제의 주성분인 비타민 C에 비해 높은 세포내 티로시나제에 대한 저해효과와 멜라닌 생성 억제효능을 가진다. 또한 인체 안전성 시험에서 어떠한 독성이나 자극도 발생하지 않아 인체사용에 있어 안전한 물질인 것으로 판명되었다. 따라서 본 발명의 플라티코딘-디는 피부 미백을 위한 화장료, 의약 등에 유용하게 사용할 수 있다.According to the present invention, platicodine-D has a higher inhibitory effect on intracellular tyrosinase and a melanin production inhibitory effect than vitamin C, which is a main component of the existing whitening agent. In addition, no toxicity or irritation occurred in human safety tests, which proved to be safe for human use. Therefore, the platicodine-D of the present invention can be usefully used in cosmetics, medicine, and the like for skin whitening.
하나의 양태로서, 본 발명은 플라티코딘-디(Platycodin D)를 포함하는 피부 미백용 화장료 조성물에 관한 것이다.In one embodiment, the present invention relates to a cosmetic composition for skin whitening comprising Platycodin D.
본 발명의 플라티코딘-디(platycodin-D)는 하기 화학식 1의 구조를 가지고 있는 식물 유래의 트리테르페노이드 사포닌계(triterpenoid saponin)의 일종이다.Platycodin-D (platycodin-D) of the present invention is a kind of triterpenoid saponin derived from plants having the structure of the following formula (1).
[규칙 제26조에 의한 보정 02.04.2009]
Figure WO-DOC-CHEMICAL-1
[Revision under Rule 26 02.04.2009]
Figure WO-DOC-CHEMICAL-1
본 발명의 플라티코딘-디는 천연 공급원(예를 들어, 도라지 등)으로부터 분리되거나, 천연 공급원으로부터 수득된 트리테르페노이드 사포닌을 화학적 개질(modification)에 의해 제조하거나, 또는 화학적으로 합성하여 제조하거나, 상업적으로 제조된 상품(예를 들어, Pharmavan 사의 Platycodin D)일 수 있다. 하나의 구체적 예로서, 본 발명의 플라티코딘-디는 도라지 뿌리에서 물, 알코올 또는 아세톤 등의 용매를 사용하여 0℃ 내지 50℃에서 추출 및 분리할 수 있으며, 이러한 추출 및 분리 방법은 당업자에게 잘 알려져 있다.Platicodin-di of the present invention may be prepared from chemical modifications, or by chemical modification of triterpenoid saponins isolated from natural sources (eg, bellflower, etc.), or obtained from natural sources. Or a commercially prepared product (eg, Platycodin D from Pharmavan). As one specific example, the platicodine-di of the present invention can be extracted and separated at 0 ° C. to 50 ° C. using a solvent such as water, alcohol or acetone at the root of bellflower, and such extraction and separation methods are available to those skilled in the art. It is well known.
본 발명의 플라티코딘-디의 미백 효과를 알아보기 위하여, 기존의 미백 화장품 원료로 사용되고 있는 비타민 C(vitamin C)와 비교하여 미백물질 스크리닝에 일반적으로 이용되는 세포내 티로시나제 활성 및 멜라닌 생성 억제효능을 측정한 결과, 동일한 농도에서 본 발명의 플라티코딘-디가 비타민 C 보다 약 10% 이상 티로시나제 활성 억제 및 멜라닌 생성 억제 효능이 우수하였다. 따라서, 본 발명의 플라티코딘-디는 미백 효과가 우수하다.In order to examine the whitening effect of the platicodine-D of the present invention, compared with vitamin C (vitamin C), which is used as a conventional whitening cosmetic raw material, intracellular tyrosinase activity and melanin production inhibitory effect generally used for screening whitening substances As a result, at the same concentration, the platycodine-diga of the present invention was superior to the inhibitory effect of tyrosinase activity and melanogenesis by about 10% or more than vitamin C. Therefore, the platicodine-di of the present invention is excellent in the whitening effect.
본 발명의 상기 화학식 1의 플라티코딘-디는 당업계에서 통상적으로 실시되는 치환기의 부가 또는 치환 반응에 의하여 얻어지는 유도체 중 멜라닌 생성 억제 및/또는 티로시나아제 활성 억제에 의한 피부 미백 효과를 나타내는 유도체를 포함한다는 것은 당업계의 기술 수준을 고려하여 당업자에게 명확하다.Platicodin-D of the formula (1) of the present invention derivatives exhibiting a skin whitening effect by inhibiting melanin production and / or tyrosinase activity of the derivatives obtained by the addition or substitution reaction of substituents commonly practiced in the art It is clear to those skilled in the art in consideration of the level of skill in the art.
본 발명의 피부 미백용 화장료 조성물에서 플라티코딘-디의 양은 전체 조성물에 대하여 0.001 내지 10 중량%, 바람직하게는 0.001 내지 5 중량%로 가 바람직하다. 0.001 중량% 미만인 경우에는 미백 효과가 너무 미약하고, 15 중량%를 초과하는 경우에는 함량의 증가에 따른 효과의 증가가 미비하고 제형상의 안정성이 확보되지 않는 문제점이 있다. The amount of platicodine-di in the cosmetic composition for skin whitening of the present invention is preferably 0.001 to 10% by weight, preferably 0.001 to 5% by weight based on the total composition. If it is less than 0.001% by weight, the whitening effect is too weak, and if it exceeds 15% by weight, there is a problem that the increase in effect due to the increase of the content is insufficient and the stability of the formulation is not secured.
본 발명의 피부 미백용 화장료 조성물은 유효 성분으로서의 플라티코딘-디 이외에 화장료 조성물에 통상적으로 이용되는 성분들을 포함할 수 있다. 예를 들어 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제 및/또는 담체가 있다. 또한 상기 화장료 조성물은 피부 미백효과를 증진시키기 위하여 피부 흡수 촉진 물질을 추가로 포함할 수 있다.The cosmetic composition for skin whitening of the present invention may include components conventionally used in cosmetic compositions in addition to Platicodin-D as an active ingredient. For example, there are conventional auxiliaries and / or carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavorings. In addition, the cosmetic composition may further include a skin absorption promoting material to enhance the skin whitening effect.
본 발명의 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클린싱, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 한정되는 것은 아니다. 보다 바람직하게는, 유연 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 클렌징 크림, 클렌징 포옴, 클렌징 워터, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.Cosmetic compositions of the present invention can be prepared in any formulation conventionally prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are not limited thereto. More preferably, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier component is aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
다른 하나의 양태로서, 본 발명은 상기 플라티코딘-디(Platycodin D)를 포함하는 피부 미백용 약제학적 조성물에 관한 것이다.In another aspect, the present invention relates to a pharmaceutical composition for skin whitening comprising Platycodin D.
본 발명의 약제학적 조성물에서, 플라티코딘-디의 양은 전체 조성물에 대하여 0.001 내지 10 중량%, 바람직하게는 0.001 내지 5 중량% 포함할 수 있다. In the pharmaceutical composition of the present invention, the amount of platicodine-di may comprise 0.001 to 10% by weight, preferably 0.001 to 5% by weight based on the total composition.
상기 약제학적 조성물은 치료 목적에 따라 약제학 분야에서 통상적인 제제로 제형화될 수 있으며, 예를 들어, 정제, 캅셀제, 산제, 과립, 현탁제, 유제, 시럽제, 유탁제, 경고제, 연고제, 스프레이제, 오일제, 겔제, 주정제, 틴크제, 욕제, 리니먼트제, 로션제, 패취제, 패드제, 크림제 등으로 제형화될 수 있다. 바람직하게는 환부에 직접 도포하는 국소투여를 목적으로 하는 피부 외용제로서, 연고제, 로션제, 스프레이제, 젤 등의 형태이다. 이들 피부외용제는 또한 치료 부위에 직접 적용될 수 있는 지지 기재(support base) 또는 매트릭스 등에 포함될 수 있으며, 지지기재의 예는 거즈 또는 붕대를 포함한다. 상기 제형화에 사용되는 약제학적 조성물은 콜로이드 형태 또는 건조된 분말 형태 등일 수 있다.The pharmaceutical composition may be formulated as a conventional agent in the pharmaceutical field according to the therapeutic purpose, for example, tablets, capsules, powders, granules, suspensions, emulsions, syrups, emulsions, warnings, ointments, sprays , Oils, gels, spirits, tinctures, baths, linings, lotions, patches, pads, creams and the like. Preferably, the topical skin preparation for topical administration directly applied to the affected area is in the form of an ointment, lotion, spray, gel or the like. These dermal external preparations may also be included in support bases or matrices that may be applied directly to the treatment site, and examples of the support bases include gauze or bandages. The pharmaceutical composition used in the formulation may be in colloidal form or dried powder form or the like.
연고제로 제형화하는 경우, 피부 표면 온도, 피부의 pH, 경피수분소실(transdermal water loss) 값, 표피의 총지질값 등을 고려하여야 하며, 바세린, 유동파라핀, 파라핀, 플라스티베이스, 실리콘, 돈지(lard), 식물유, 왁스, 정제 라놀린(purified lanolin) 등의 유지성 기재, 수용성 기재, 유제성 기재, 현탁성 기재 등과 배합하여 제형화한다. 이러한 연고제는 산화방지제(예, 토코페롤, BHA, BHT, NDGA 등), 방부제(예, 페놀성 물질, 클로로부탄올, 벤질알코올, 파라벤류, 안식향산 등), 보습제(예, 글리세린, 프로필렌클리콘, 소르비톨), 용해보조제(예, 에탄올, 프로필렌글리콜), 연화보조제(예, 유동파라핀, 글리세린, 프로필렌글리콜, 게면활성제 등) 등의 첨가제와 함께 배합될 수 있다. When formulated as an ointment, the skin surface temperature, skin pH, transdermal water loss value, epidermal total lipid value, etc. should be considered. Vaseline, liquid paraffin, paraffin, plastibase, silicone, pork (lard), vegetable oils, waxes, formulated in combination with oil-soluble substrates, such as water-soluble substrates, emulsion bases, suspension bases, such as purified lanolin. These ointments include antioxidants (e.g. tocopherol, BHA, BHT, NDGA, etc.), preservatives (e.g. phenolic substances, chlorobutanol, benzyl alcohol, parabens, benzoic acid, etc.), moisturizers (e.g. glycerin, propylene glycol, sorbitol). ), Dissolution aids (eg, ethanol, propylene glycol), softening aids (eg, liquid paraffin, glycerin, propylene glycol, surfactants, etc.) and the like.
로션제로 제형화하는 경우, 용액형, 현탁형 또는 유제형 등의 로션제로 제조될 수 있으며, 피부에 바르는 로션의 경우 예를 들어 200cps 내지 500cps의 점성을 가지도록 제조할 수 있으며, 도포시 부드러운 느낌을 주기 위하여 글리세린, 프로필렌글리콜 같은 습윤제를 배합하여 제조하는 것이 바람직하다. When formulated into a lotion, it may be prepared in a lotion such as solution, suspension or emulsion type, and in the case of a lotion applied to the skin, for example, may be prepared to have a viscosity of 200 cps to 500 cps, and a soft feeling when applied. It is preferable to prepare a compound by combining a humectant such as glycerin and propylene glycol.
스프레이제로 제형화하는 경우, 수분산된 농축물 또는 습윤 분말이 분산되도록 추진제 등이 첨가제와 함께 배합될 수 있다. When formulated with a spray, a propellant or the like may be combined with the additives to disperse the dispersed dispersion or wet powder.
패취제로 제형화하는 경우, 피부를 통한 화합물의 흡수를 증가시키기 위해서 흡수촉진제를 사용할 수 있다.When formulated as a patch, absorption accelerators can be used to increase the absorption of the compound through the skin.
본 발명의 약제학적 조성물은 약제학적 조성물의 제조에 통상적으로 사용되는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 약제학적 조성물의 제형으로는 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 연고, 크림 등의 외용제, 좌제 및 멸균 주사용액 등을 비롯하여 약제학적 제제에 적합한 어떠한 형태로든 제형화하여 사용할 수 있다.Formulations of the pharmaceutical compositions of the present invention include powders, granules, tablets, capsules, suspensions, emulsions, syrups, oral formulations such as aerosols, external preparations such as ointments, creams, suppositories, sterile injectable solutions, etc. It may be used in any form suitable for pharmaceutical formulations, including.
본 발명에 따른 약제학적 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 비경구, 경구 등의 다양한 경로로 투여될 수 있으며, 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다. 이때, 비경구 경로로는 경피 투여가 바람직하며, 그 중에서도 국소 도포가 가장 바람직하다. 상기 국소 투여는 전신 효과를 가져오는 경피 전달을 포함한다. 국소 투여하는 경우, 부형제(예, 락토스, 전분, 셀룰로스, 유당, 폴리에틸렌 글리콜 등), 윤활제(예, 마그네슘 스테아레이트, 스테아르산, 글리세릴 베헤네이트(behenate), 활석 등), 보존제(예, 벤질알코늄 클로라이드 등) 등을 포함할 수 있다. The pharmaceutical composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes such as parenteral, oral, and all modes of administration can be expected, for example, oral, It may be administered by rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection. At this time, as a parenteral route, transdermal administration is preferred, and topical application is most preferred. The topical administration includes transdermal delivery resulting in systemic effects. When administered topically, excipients (e.g. lactose, starch, cellulose, lactose, polyethylene glycol, etc.), lubricants (e.g. magnesium stearate, stearic acid, glyceryl behenate, talc, etc.), preservatives (e.g. benzyl) Alconium chloride, etc.), and the like.
본 발명의 약제학적 조성물은 약제학적으로 유효한 양으로 투여한다. 본 발명에서 "약제학적으로 유효한 양"은 의학적 치료 또는 예방에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료 또는 예방하기에 충분한 양을 의미하며, 유효 용량 수준은 질환의 종류 및 이의 중증도; 약물의 활성; 환자의 연령, 체중, 건강, 성별; 환자의 약물에 대한 민감도; 사용된 특정 추출물의 투여 시간, 투여 경로 및 배출 비율; 치료 기간; 사용된 특정 추출물과 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 일반적으로, 외용제의 경우 1일당 1.0 내지 3.0㎖로 이를 1일 1 내지 5회 도포하여 1개월 이상 계속하는 것이 좋다. 또한, 경구형 제형의 경우 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 0.1 내지 100 ㎎/㎏의 양을 1일 1회 내지 수회 투여할 수 있다. The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, “pharmaceutically effective amount” means an amount sufficient to treat or prevent a disease at a reasonable benefit / risk ratio applicable to medical treatment or prophylaxis, and an effective dose level means the type of disease and its severity; Activity of the drug; The age, body weight, health and sex of the patient; Sensitivity to the drug of the patient; The time of administration, route of administration, and rate of excretion of the specific extract used; Duration of treatment; It may be determined according to factors including drugs used in combination or coincidental with the specific extract used and factors well known in the medical arts. In general, in the case of external preparations it is preferable to apply it at 1.0 to 3.0ml per day 1 to 5 times a day to continue for more than one month. In addition, the oral dosage form may vary depending on the age, sex, and weight of the patient, but the amount of 0.1 to 100 mg / kg may be administered once to several times a day.
다른 하나의 양태로서, 본 발명은 본 발명의 상기 화장료 조성물 또는 약제학적 조성물을 인간을 포함한 포유동물의 피부에 도포하여 피부를 미백하는 방법에 관한 것이다.In another aspect, the present invention relates to a method for whitening skin by applying the cosmetic composition or pharmaceutical composition of the present invention to the skin of a mammal, including a human.
본 발명에 있어서, “미백”은 노화, 자외선, 오염된 환경 등의 다양한 원인에 의해 멜라닌 색소가 침착되어 발생되는 피부의 흑화를 방지하거나 개선하는 것을 말한다. In the present invention, "whitening" refers to preventing or improving blackening of the skin caused by the deposition of melanin due to various causes such as aging, ultraviolet rays, contaminated environment, and the like.
구체적 실시에서, 본 발명의 플라티코딘-디는 피부 미백을 목적으로 화장품 등의 원료로 종래부터 사용되고 있는 비타민 C(vitamin C)와 비교하더라도 약 10% 이상 티로시나제 활성 억제 및 멜라닌 생성 억제 효능이 우수하였다. 따라서 본 발명의 화장료 조성물 및 약제학적 조성물에 유효 성분으로 포함되는 플라티코딘-디는 피부 미백 효과가 매우 우수하여 상기 조성물을 피부에 도포하여 피부를 효과적으로 미백할 수 있을 것이다.In a specific embodiment, the platicodine-D of the present invention is excellent in inhibiting tyrosinase activity and inhibiting melanin production by at least about 10% even when compared to vitamin C (vitamin C) conventionally used as a raw material for cosmetics for the purpose of skin whitening. It was. Therefore, Platicodine-D, which is included as an active ingredient in the cosmetic composition and the pharmaceutical composition of the present invention, has an excellent skin whitening effect, and thus the skin may be effectively whitened by applying the composition to the skin.
본 발명의 구체적 실시에서 플라티코딘-디에 대한 피부누적 자극시험 결과 플라티코딘-디는 천연 물질로서 인체에 무해한 물질임이 밝혀졌다. 따라서, 본 발명의 플라티코딘-디는 독성 및 부작용이 거의 없으므로 장기간 사용 시에도 안심하고 사용할 수 있으며, 특히 상기한 바와 같은 화장료 조성물 및 약제학적 조성물 등에 안전하게 적용할 수 있다.In a specific embodiment of the present invention, the cumulative skin irritation test against platicodine-D was found to be a natural substance that is harmless to humans. Therefore, the platicodine-D of the present invention has little toxicity and side effects, so it can be used safely even in long-term use, and in particular, it can be safely applied to cosmetic compositions and pharmaceutical compositions as described above.
이하, 실시예를 통하여 본 발명을 더욱 상세하게 설명한다. 하기 실시예는 단지 본 발명을 보다 구체적으로 설명하기 위한 것으로서 본 발명을 이에 제한하고자 함이 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples. The following examples are only intended to illustrate the present invention in more detail and are not intended to limit the present invention thereto.
실시예 1 : 플라티코딘-디에 의한 멜라닌 생성 억제효과 측정Example 1 Measurement of Melanin Inhibition Effect by Platicodin-D
쥐의 색소세포(B16 melanoma cells)를 이용하여 플라티코딘-디(Sigma)에 의한 멜라닌 생성 억제효과를 측정하였으며, 이를 멜라닌 생성을 억제하는 것으로 알려진 비타민 C에 의한 멜라닌 생성 억제효과와 비교하였다.B16 melanoma cells were used to measure the inhibitory effect of melanin production by Platicodin-D (Sigma), and this was compared with the melanin production inhibitory effect of vitamin C, which is known to inhibit melanogenesis.
본 실험은 murine melanoma(B-16 F10) 세포를 10%의 FBS(fetal bovine serum)가 함유된 DMEM 배지로 6-웰 플레이트에 웰당 1×105 개로 접종한 후, 5 % CO2 37℃에서 세포가 웰 바닥에 약 80 % 이상 부착될 때까지 배양하였다. 배양 후 배지를 제거하고 플라티코딘-디 및 비타민 C를 적당 농도로 희석된 DMEM배지에 교체하고, 5% CO2, 37℃에서 3일간 배양하였다. 플라티코딘-디의 농도범위는 세포독성이 없는 0.1 uM, 0.5 uM, 1 uM로 결정하였다. 비타민 C의 농도범위는 플라티코딘-디와 동일하게 0.1 uM, 0.5 uM, 1 uM로 하였다. 상기 배양 후 배지를 제거하고 수집된 세포를 PBS(phosphated buffer saline)로 세척하고, 이것을 트립신으로 처리하여 세포를 회수하였다. 회수된 세포는 hematocytometer를 이용하여 세포수를 측정하고 5,000 내지 10,000 rpm으로 10분간 원심분리한 다음 상등액을 제거하여 pellet을 얻었다. 이 세포 pellet을 60℃에서 건조한 후, 10% DMSO가 함유된 1M 수산화나트륨액 100㎕ 를 넣어 60℃ 항온조에서 세포내 멜라닌을 얻었다. 이 액을 가지고 microplate reader로 490 nm에서 흡광도를 측정하여 세포 일정 수당 멜라닌 양을 구하였다. 그 결과를 하기 표 1에 나타내었다.This experiment was performed using murine melanoma (B-16 F10) cells in DMEM medium containing 10% fetal bovine serum (FBS) in 6-well plates at 1 × 10 per well.5 After inoculation with dogs, 5% CO2And Cells were incubated at 37 ° C. until they were at least about 80% adhered to the bottom of the well. After incubation, remove the medium and replace Platicodin-D and vitamin C in a DMEM medium diluted to the appropriate concentration, 5% CO2,Incubated at 37 ° C. for 3 days. The concentration range of Platicodin-D was determined to be 0.1 uM, 0.5 uM, 1 uM without cytotoxicity. The concentration range of vitamin C was 0.1 uM, 0.5 uM, 1 uM in the same manner as Platicodin-D. After the culture, the medium was removed, and the collected cells were washed with PBS (phosphated buffer saline) and treated with trypsin to recover the cells. The recovered cells were counted using a hematocytometer, centrifuged at 5,000 to 10,000 rpm for 10 minutes, and then the supernatant was removed to obtain pellets. The cell pellet was dried at 60 ° C., and 100 µl of 1 M sodium hydroxide solution containing 10% DMSO was added to obtain intracellular melanin in a 60 ° C. thermostat. Using this solution, the absorbance at 490 nm was measured with a microplate reader to determine the amount of melanin per cell. The results are shown in Table 1 below.
표 1
시료 처리 농도 (uM) 멜라닌 생성 억제율 (%)
비타민 C 0.1 0
비타민 C 0.5 0
비타민 C 1 2
플라티코딘-디 0.1 0
플라티코딘-디 0.5 34
플라티코딘-디 1 52
Table 1
sample Treatment Concentration (uM) Melanin production inhibition rate (%)
Vitamin c 0.1 0
Vitamin c 0.5 0
Vitamin c One 2
Platicodin-D 0.1 0
Platicodin-D 0.5 34
Platicodin-D One 52
상기 표 1에 기재된 바와 같이, 동일 처리 농도에서 플라티코딘-디가 비타민 C보다 우수한 멜라닌 생성 억제율을 나타내었다. As shown in Table 1 above, at the same treatment concentration, platicodine-di showed better melanogenesis inhibition than vitamin C.
실시예 2 : 플라티코딘-디에 의한 세포내 티로시나제 활성억제 효과 측정Example 2 Measurement of Inhibitory Effect of Intracellular Tyrosinase Activity by Platicodin-D
쥐의 색소세포(B16 melanoma cells)를 이용하여 플라티코딘-디에 의한 멜라닌 생성 억제효과를 측정하고, 이를 멜라닌 생성을 억제하는 것으로 알려진 비타민 C에 의한 세포내 티로시나제 활성 억제효과와 비교하였다.Rat pigment cells (B16 melanoma cells) were used to measure the inhibitory effect of melanin production by placodin-di and compared with the inhibitory effect of intracellular tyrosinase activity by vitamin C, which is known to inhibit melanin production.
본 실험은 murine melanoma(B-16 F1) 세포를 10%의 FBS (fetal bovine serum)가 함유된 DMEM 배지로 6-well plate에 well당 1×105 개로 접종한 후 5 % CO2, 37℃에서 세포가 well 바닥에 약 80 % 이상 부착될 때까지 배양하였다. 배양 후 배지를 제거하고 플라티코딘-디 및 비타민 C를 적당 농도로 희석된 DMEM배지에 교체하고, 5% CO2, 37℃에서 3일간 배양하였다. 플라티코딘-디 및 비타민 C의 농도범위는 상기 실시예 1과 동일하게 0.1 uM, 0.5 uM, 1 uM 였다. 상기 배양 후 배지를 제거하고 수집된 세포를 PBS(phosphated buffer saline)로 세척하고, 이것을 트립신으로 처리하여 세포를 회수하였다. 회수된 세포는 hematocytometer를 이용하여 세포수를 측정한 후 5,000 내지 10,000 rpm으로 10분간 원심분리한 다음 상등액을 제거하여 pellet을 얻었다. 이 세포 pellet를 lysis buffer를 이용하여 분쇄한 후, 12,000rpm으로 10분간 원심분리하여 상층액을 수집하였다. 이 액을 가지고 microplate reader로 492 nm에서 흡광도를 측정하여 세포 일정수당 티로시나제 활성을 구하였다. 그 결과를 하기 표 2에 나타내었다.In this experiment, murine melanoma (B-16 F1) cells were inoculated in DMEM medium containing 10% FBS (fetal bovine serum) at 1 × 10 5 per well in a 6-well plate, followed by 5% CO 2 at 37 ° C. The cells were cultured until at least 80% of the cells adhered to the well bottom. After incubation, the medium was removed and Platicodin-D and Vitamin C were replaced with DMEM medium diluted to appropriate concentrations and incubated at 5% CO 2, 37 ° C. for 3 days. The concentration ranges of platicodine-di and vitamin C were 0.1 uM, 0.5 uM, and 1 uM as in Example 1. After the culture, the medium was removed, and the collected cells were washed with PBS (phosphated buffer saline), which was treated with trypsin to recover the cells. The recovered cells were counted using a hematocytometer, centrifuged at 5,000 to 10,000 rpm for 10 minutes, and then the supernatant was removed to obtain pellets. The cell pellet was pulverized using lysis buffer, and the supernatant was collected by centrifugation at 12,000 rpm for 10 minutes. Using this solution, the absorbance was measured at 492 nm using a microplate reader to determine the cell number tyrosinase activity. The results are shown in Table 2 below.
표 2
시료 처리 농도 (uM) 세포내 티로시나제 활성 억제율 (%)
비타민 C 0.1 0
비타민 C 0.5 0
비타민 C 1 4
플라티코딘-디 0.1 1
플라티코딘-디 0.5 33
플라티코딘-디 1 49
TABLE 2
sample Treatment Concentration (uM) % Inhibition of intracellular tyrosinase activity
Vitamin c 0.1 0
Vitamin c 0.5 0
Vitamin c One 4
Platicodin-D 0.1 One
Platicodin-D 0.5 33
Platicodin-D One 49
상기 표 2에 기재된 바와 같이, 동일 처리 농도에서 플라티코딘-디가 비타민 C보다 우수한 세포내 티로시나제 억제율을 보였다. As shown in Table 2 above, at the same treatment concentration, platycodine-di showed better intracellular tyrosinase inhibition than vitamin C.
실시예 3 : 동물수준에서의 미백 효과 평가Example 3 Evaluation of Whitening Effect at Animal Level
사람과 유사하게 자외선에 의해 색소침착이 생긴다고 알려진 갈색 몰모토(Tortoiseshell guinea pigs; Brown guinea pigs)를 사용하여 플라티코딘-디에 의한 미백효과를 측정하였다. Similar to humans, the whitening effect by placodin-di was measured using brown malto (Tortoiseshell guinea pigs; known as brown guinea pigs) known to cause pigmentation by ultraviolet rays.
상기 갈색 몰모토에서 자외선(UV)에 의한 색소침착을 유발하기 위하여, 갈색 몰모토 배위의 털을 제거한 피부에 3 X 3 cm2의 정방형 창문이 뚫린 차광용 알루미늄 호일을 접착시킨 후, SE lamp(파장 290-320 nm, Toshiba)로 자외선을 조사하였다(총조사 에너지량 = 1350 mJ/cm2). 자외선 조사후 알루미늄 호일을 벗겨내고 아래와 같은 방법으로 시료(플라티코딘-디 및 비타민 C)를 도포하였다. 자외선 조사후 2, 3일 후에 색소침착이 나타났으며, 약 2주 후에 최고에 도달하였고, 이 때부터 각 시료를 도포하였다.In order to cause pigmentation by ultraviolet (UV) in the brown molemoto, a light shielding aluminum foil having a square window of 3 × 3 cm 2 is adhered to the skin from which the hair of the brown molemoto coordination is removed, and then SE lamp ( Ultraviolet rays were irradiated with a wavelength of 290-320 nm (Toshiba) (total irradiation energy amount = 1350 mJ / cm 2 ). After UV irradiation, the aluminum foil was peeled off and a sample (platicodine-di and vitamin C) was applied in the following manner. Pigmentation appeared 2 or 3 days after the UV irradiation, and reached a peak after about 2 weeks, and each sample was applied therefrom.
도포 회수는 1일 1회 또는 2회로, 50일간 계속하였다. 시료는 특정한 용매(Propylene Glycol: Ethanol: Water = 5: 3: 2의 혼합용매)를 사용하여 용해 및 희석하였으며, 면봉으로 도포하고, 다른 부위에 반드시 용매를 도포하는 대조부위를 마련하였다. 효과 판정과 함께 누적자극성 여부도 관찰하였다. The number of coatings was continued once or twice a day for 50 days. Samples were dissolved and diluted with a specific solvent (Propylene Glycol: Ethanol: Water = 5: 3: 2 mixed solvent), coated with a cotton swab, and prepared a control site for necessarily applying a solvent to other sites. Along with the determination of effects, the cumulative stimulus was also observed.
색차계(미놀타 CR2002 chromameter)를 사용하여 피부의 흑백정도를 측정하여 효과를 판정하였으며, 그 결과를 하기 표 3에 나타내었다. 색을 표시하는데는 L*A*B* 표색계를 사용하며, 본 발명에서는 L*값을 지표로 하였다. L*값은 표준 백판으로 교정하며, L*값은 1개 부위에 5회 이상 반복하여 측정하였고, 색소침착을 균등하게 하였다. 도포 시작시점과 완료시점에서의 피부색의 차이(L*)를 구하고 이 값으로 효과를 판정하였다. L* 값을 시료도포 부위와 대조군 부위에 대해서 구한 후 비교하면 미백물질의 효과를 알 수 있다. 그 결과를 하기 표 3에 나타내었다.The effect was determined by measuring the degree of black and white of the skin using a color difference meter (Minolta CR2002 chromameter), the results are shown in Table 3 below. L * A * B * colorimeter is used to display color, and L * value was used as an index in this invention. L * value was calibrated with a standard whiteboard, and L * value was measured 5 times or more at one site, and pigmentation was equalized. The difference (L * ) between the skin color at the start of application and at the end of application was determined and the effect was judged by this value. Comparing the L * value for the sample application site and the control site and comparing the effect of the whitening material can be seen. The results are shown in Table 3 below.
[실험식 1][Equation 1]
L* = 도포 00일 후의 L*값 - 도포 개시일의 L*L * = L * value after 00 days application - L * value of the coating start date
표 3
시료 처리 농도 (%) 미백효과 (L)
플라티코딘-디 0.2 0.42
플라티코딘-디 1.0 0.58
비타민 C 1.0 0.44
대조군 0.30
TABLE 3
sample Treatment Concentration (%) Whitening Effect (L)
Platicodin-D 0.2 0.42
Platicodin-D 1.0 0.58
Vitamin c 1.0 0.44
Control 0.30
상기 표 3에 기재된 바와 같이, 플라티코딘-디는 비타민 C보다 우수한 미백효과를 보였으며, 시험물질 도포시험 중 누적 자극을 보인 것은 관찰되지 않아 안전성 또한 우수한 것으로 나타났다.As shown in Table 3, Platicodin-D showed a better whitening effect than vitamin C, and cumulative irritation was not observed during the test application of the test substance, and thus safety was also excellent.
실시예 4 : 플라티코딘-디의 인체 피부에 대한 안전성 확인 실험Example 4 Safety Confirmation Test of Platicodin-D on Human Skin
4-1. 플라티코딘-디를 포함한 피부외용제의 제조4-1. Preparation of external skin preparations including Platicodin-D
상기와 같이 미백효과가 우수하다고 판명된 플라티코딘-디가 인체피부에도 안전한지 확인하기 위하여, 플라티코딘-디 및 비타민 C을 함유한 피부외용제를 제조하고 이에 의한 피부 안전성 검증 실험을 수행하였다.In order to confirm that the placodin-di, which was found to be excellent in the whitening effect as described above, is safe for human skin, an external skin preparation containing placodin-di and vitamin C was prepared and skin safety verification experiments were conducted. .
플라티코딘-디와 비타민 C을 함유한 피부외용제는 하기 표 4의 성분함량으로 제조하였다. 하기 표 4에서 대조군은 티로시나제 저해제를 포함하지 않은 피부외용제이며, 각각 시험군 1과 시험군 2는 플라티코딘-디와 비타민 C을 포함한 피부외용제이다.Skin external preparations containing Platicodin-di and vitamin C were prepared by the ingredient contents of Table 4 below. In the following Table 4, the control group is an external skin preparation that does not include a tyrosinase inhibitor, and test group 1 and test group 2 are external skin preparations including platicodine-D and vitamin C, respectively.
피부외용제 제조를 위하여, 정제수, 글리세린, 부틸렌글리콜을 혼합하고 70℃에서 용해하였으며(수상파트), 상기 세 성분과 트리메탄올아민을 제외한 나머지 성분을 70℃ 에서 용해하였다(유상파트). 상기 오일파트를 수상파트에 첨가하고 호모믹서(일본 Tokushu Kika사)로 교반하여 1차 유화하였고, 여기에 트리메탄올아민을 최종 첨가하였다. 혼합액에 생성된 기포를 제거한 후, 실온으로 냉각시켜 피부외용제를 제조하였다.For the preparation of external skin preparations, purified water, glycerin and butylene glycol were mixed and dissolved at 70 ° C. (water part), and the other components except the above three components and trimethanolamine were dissolved at 70 ° C. (oil part). The oil part was added to the water part and stirred with a homomixer (Tokushu Kika, Japan) to emulsify first, to which trimethanolamine was finally added. After removing the bubbles generated in the mixed solution, and cooled to room temperature to prepare a skin external preparation.
표 4
성분 함량 (%)
대조군 시험군 1 시험군 2
정제수 72 72 72
글리세린 8.0 8.0 8.0
부틸렌글리콜 4.0 4.0 4.0
플라티코딘-디 0 1.0 0
비타민 C 0 0 1.0
카프릴릭 카프리 트리글리세라이드 8.0 8.0 8.0
스쿠알란 5.0 5.0 5.0
세테아릴 글루쿠사이드 1.5 1.5 1.5
소르비탄 스테아레이트 0.4 0.4 0.4
세테아릴 알코올 1.0 1.0 1.0
트리메탄올아민 0.1 0.1 0.1
총중량 100 100 100
Table 4
ingredient content (%)
Control Test group 1 Test group 2
Purified water 72 72 72
glycerin 8.0 8.0 8.0
Butylene glycol 4.0 4.0 4.0
Platicodin-D 0 1.0 0
Vitamin c 0 0 1.0
Caprylic Capri Triglyceride 8.0 8.0 8.0
Squalane 5.0 5.0 5.0
Cetearyl Glucoside 1.5 1.5 1.5
Sorbitan stearate 0.4 0.4 0.4
Cetearyl Alcohol 1.0 1.0 1.0
Trimethanolamine 0.1 0.1 0.1
Gross weight 100 100 100
4-2. 피부누적 자극 시험4-2. Skin accumulation stimulation test
상기 실시예 4-1에서 제조한 각 피부외용제를 사용하여 건강한 30명의 성인을 대상으로 윗팔뚝 부위에 격일로 총 9회의 24시간 누적첩포를 시행하는 것에 의하여 플라티코딘-디가 피부에 자극을 주는지의 여부를 측정하였다.Platicodine-D stimulates the skin by performing a total of nine 24-hour cumulative blisters on the upper forearm every other day in 30 healthy adults using each skin preparation prepared in Example 4-1. It was measured whether or not giving.
첩포 방법은 핀 챔버(Finn chamber, Epitest Ltd, 핀란드)를 이용하였다. 챔버에 상기 각 피부외용제를 15ul씩 적하한 후 첩포를 실시하였다. 매회 피부에 나타난 반응의 정도를 하기 실험식 2를 이용하여 점수화 하였으며, 그 결과를 하기 표 5에 나타내었다.The patch method used the fin chamber (Finn chamber, Epitest Ltd, Finland). 15ul of each said skin external preparation was dripped at the chamber, and the patch was performed. The degree of response to the skin each time was scored using the following Experimental Formula 2, and the results are shown in Table 5 below.
[실험식 2][Equation 2]
평균반응도=[[반응지수x 반응도/ 총피검자수 x 최고점수 (4점)] x 100 ] ◎검사회수 (9회)Average responsiveness = [[response index x responsiveness / total number of subjects x highest score (4 points)] x 100] ◎ Number of tests (9 times)
이 때, 반응도에서 ± 는 1점, +는 2점, ++는 4점의 점수를 부여하며, 평균반응도가 3 미만일 때 안전한 조성물로 판정하였다.At this time, ± 1 point, + 2 points, + + 4 points in the reaction degree, and the average response was determined to be a safe composition when less than 3.
표 5
시험물질 반응이 나타난 피검자 수 평균반응도
1주 2주 3주
1차 2차 3차 4차 5차 6차 7차 8차 9차
± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++
대조군 1 - - - - - - - - - - - - - - - - - - - - - - - - - - 0.09
시험군 1 1 - - 1 - - - - - - - - - - - - - - - - - - - - - - - 0.13
시험군 2 3 - - 1 - - - - - - - - - - - - - - - - - - - - - - - 0.37
피검인원 30 30 30 30 30 30 30 30 30
Table 5
Test substance Number of subjects with response Average reactivity
1 week 2 weeks 3 weeks
Primary Secondary 3rd 4th 5th 6th 7th 8th 9th
± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++
Control One - - --- --- --- --- --- --- --- --- 0.09
Test group 1 One - - One - - --- --- --- --- --- --- --- 0.13
Test group 2 3-- One - - --- --- --- --- --- --- --- 0.37
Inspector 30 30 30 30 30 30 30 30 30
상기 표 5에서 시험군 1의 경우, ±, +, ++에 해당하는 사람의 수가 각각 1명, 0명, 0명이었고, 그 외 나머지는 반응이 나타나지 않았다. 상기 기재된 식에 따라 계산하면 [(1x2)/(20x4)]x 100/9=0.13로 평균 반응도가 0.37이 되어 3 이하가 되어 안전한 조성물로 판단되었다. In Table 5, in the case of test group 1, the number of persons corresponding to ±, +, and ++ was 1, 0, and 0, respectively, and the rest did not appear. When calculated according to the formula described above, the average reactivity was [3x2] / (20x4)] x100 / 9 = 0.13 to 0.37, and 3 or less was judged to be a safe composition.
따라서 상기 표 5에 기재된 바와 같이, 플라티코딘-디(시험군 1)를 포함한 피부외용제는 대조군이나 비타민 C을 포함한 피부 외용제와 같이 뚜렷한 누적자극 양상을 나타내지 않았으며 인체 피부에 안전한 물질로 판정되었다.Therefore, as shown in Table 5, the external skin preparations containing Platicodin-D (Test Group 1) did not show a distinct cumulative stimulation pattern as the external skin preparations containing the control or vitamin C and was determined to be a safe substance for human skin. .
본 발명의 플라티코딘-디는 기존 미백제의 주성분인 비타민 C에 비해 높은 세포내 티로시나제에 대한 저해효과와 멜라닌 생성 억제효능을 가진다. 또한 인체 안전성 시험에서 어떠한 독성이나 자극도 발생하지 않아 인체사용에 있어 안전한 물질인 것으로 판명되었다. 따라서 본 발명은 피부 미백을 위한 화장료, 의약 등에 유용하게 사용할 수 있다.Platicodin-D of the present invention has a higher inhibitory effect on intracellular tyrosinase and a melanin production inhibitory effect than vitamin C, which is a main component of the existing whitening agent. In addition, no toxicity or irritation occurred in human safety tests, which proved to be safe for human use. Therefore, the present invention can be usefully used in cosmetics, medicine and the like for skin whitening.

Claims (6)

  1. 플라티코딘-디를 유효성분으로 포함하는 피부미백용 화장료 조성물.A cosmetic composition for skin whitening comprising Platicodin-D as an active ingredient.
  2. 제1항에 있어서, 상기 조성물은 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클린싱, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이로 구성된 군으로부터 선택되는 제형을 갖는 것을 특징으로 하는 조성물.The group of claim 1 wherein the composition consists of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray A composition characterized by having a formulation selected from.
  3. 플라티코딘-디를 유효성분으로 포함하는 피부 미백용 약제학적 조성물.A pharmaceutical composition for skin whitening comprising Platicodin-D as an active ingredient.
  4. 제1항 내지 제3항 중 어느 한 항에 있어서, 플라티코딘-디가 전체 조성물의 총 중량에 대하여 0.001 내지 10 중량% 포함되는 조성물.The composition of claim 1, wherein the platicodine-di is comprised between 0.001 and 10% by weight relative to the total weight of the total composition.
  5. 제1항 또는 제2항의 조성물을 인간을 포함한 포유동물의 피부에 도포하는 단계를 포함하는 피부 미백 방법.A method for skin whitening comprising applying the composition of claim 1 to a skin of a mammal, including a human.
  6. 제5항에 있어서, 플라티코딘-디가 전체 조성물의 총 중량에 대하여 0.001 내지 10 중량% 포함되는 조성물.6. The composition of claim 5, wherein the platicodine-di comprises 0.001 to 10% by weight relative to the total weight of the total composition.
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