WO2008130130A1 - Compositions for improving skin conditions comprising alum - Google Patents

Compositions for improving skin conditions comprising alum Download PDF

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Publication number
WO2008130130A1
WO2008130130A1 PCT/KR2008/002152 KR2008002152W WO2008130130A1 WO 2008130130 A1 WO2008130130 A1 WO 2008130130A1 KR 2008002152 W KR2008002152 W KR 2008002152W WO 2008130130 A1 WO2008130130 A1 WO 2008130130A1
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WIPO (PCT)
Prior art keywords
composition
alum
effect
skin
present
Prior art date
Application number
PCT/KR2008/002152
Other languages
French (fr)
Inventor
Deok Hoon Park
Eunsun Jung
Jong Sung Lee
Original Assignee
Biospectrum, Inc.
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
Application filed by Biospectrum, Inc. filed Critical Biospectrum, Inc.
Publication of WO2008130130A1 publication Critical patent/WO2008130130A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/26—Aluminium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • the present invention relates to a composition for improving skin conditions, and more particularly to a composition for improving skin conditions comprising alum, in which the composition has an excellent product stability, can be safely used without skin complications, and has an excellent anti- wrinkle effect, skin whitening effect, anti-obesity effect, anti-inflammatory effect, and excellent effects of preventing hair loss and stimulating hair growth.
  • collagenase which is a collagen degradation enzyme that reduces collagen synthesis and content, among various factors such as moisture content, collagen content, and immune response against environmental stress.
  • collagenase a collagen degradation enzyme that reduces collagen synthesis and content, among various factors such as moisture content, collagen content, and immune response against environmental stress.
  • the effect of alum on collagen and collagenase extract has not been reported. However, in experiments described in the present invention, it was found that alum has effects of enhancing collagen synthesis and inhibiting collagenase activity.
  • the present inventors have made intensive investigation to find a cosmetic material having high safety and stability and excellent efficacy of improving skin conditions. They found that alum has a variety of efficacies such as improvement of wrinkles and enhancement of skin whitening, as well as excellent safety and stability.
  • the present inventors have made an effort to develop a novel substance having an excellent anti- wrinkle effect, skin whitening effect, anti-inflammatory effect, anti- obesity effect, and excellent effects of preventing hair loss and stimulating hair growth, and having high stability without skin complications. As a result, they found that a composition comprising alum as an effective ingredient has excellent efficacy and safety to provide an excellent anti- wrinkle effect, skin whitening effect, antiinflammatory effect, and excellent effects of preventing hair loss and stimulating hair growth, thereby completing the present invention.
  • the present invention provides a composition for improving skin conditions comprising alum as an effective ingredient, in which the improvement of skin conditions includes an anti-wrinkle effect, a skin whitening effect, an antiinflammatory effect, and effects of stimulating hair growth and preventing hair loss.
  • the present invention provides an anti-obesity composition, comprising alum as an effective ingredient.
  • the present inventors have made an effort to develop a novel substance having an excellent anti- wrinkle effect, skin whitening effect, anti-inflammatory effect, anti- obesity effect, and excellent effects of preventing hair loss and stimulating hair growth, and having high stability without skin complications.
  • a composition comprising alum as an effective ingredient has excellent efficacy and safety to provide an excellent anti- wrinkle effect, skin whitening effect, antiinflammatory effect, anti-obesity effect, and excellent effects of preventing hair loss and stimulating hair growth.
  • Alum also called alumen, is a double sulfate of aluminum sulfate and a monovalent metal such as alkali metals than lithium), thallium, and ammonium.
  • Alum has the typical formula MIA (SO ) -12H O or MI SO -Al (SO ) -24H O, and may be called
  • potassium alum (kalinite; KAl(SO ) -12H O), ammonium alum (chermigite; (NH
  • Alum 4 2 2 with other trivalent metal ions than aluminum, may also be referred to as alum, and called ammonium-iron alum or rubidium-cobalt alum according to each metal ion.
  • Alum is produced by crystallization from a mixed aqueous solution (1:1) of monovalent metal sulfate and trivalent metal sulfate, and the produced crystalline powder is readily soluble, and more soluble by heating in water.
  • Aluminum sulfate [Al (SO ) -18H O] is prepared from aluminum hydroxide in hot, concentrated sulfuric
  • Alum is known to show efficacy such as hemostasis, antidiarrhea, detoxification and astriction, and also known to be effective in the improvement of melena, Trichomonal vaginitis, and osmidrosis.
  • alum is used as an adjuvant, which is co-injected with an antigen to enhance the immune response, and is reported to have effects of soothing skin, preventing dental caries, and improving allergy.
  • the alum of the present invention has a structure of the following Formula 1.
  • the composition of the present invention has an effect of improving wrinkles.
  • the composition of the present invention exhibits an excellent effect of improving wrinkles by molecular mechanism responsible for inhibition of collagenase activity and stimulation of collagen synthesis, which will be described in detail in the following Examples.
  • effect of improving wrinkles encompasses typical skin-protecting effects (prevention and removal of wrinkles, inhibition of skin aging or the like).
  • composition for improving skin conditions of the present invention also has an excellent skin whitening effect, anti-inflammatory effect, and excellent effects of stimulating hair growth and preventing hair loss.
  • effect of preventing hair loss or “effect of stimulating hair growth” is used as the same meaning, and has the same meaning as used in the art.
  • composition of the present invention has an excellent anti-obesity effect.
  • the alum of Formula 1 of the present invention includes derivatives that exhibit the effect of improving wrinkles due to stimulation of collagen synthesis and/or inhibition of collagenase (MMP-I) activity, or exhibit a skin whitening effect, or an effect of stimulating hair growth or preventing hair loss, among its derivatives produced by addition or substitution of substituent.
  • MMP-I collagenase
  • the effective ingredient, alum is contained in an amount of 0.00001 to 10.0 wt%, more preferably 0.0001 to 10 wt%, and most preferably 0.0001 to 5 wt%, based on the total weight of the composition. If the content is less than 0.00001 wt%, the effect is not sufficient, and if the content is more than 10.0 wt%, the effect is slightly increased, whereas there is a problem in the stability upon formulation.
  • the composition of the present invention is a cosmetic composition.
  • the cosmetic composition of the present invention may include additives commonly used in cosmetic formulations, for example, conventional auxiliary agents such as an antioxidant, a stabilizer, a solubilizing agent, a vitamin, a pigment, and a scent, and a carrier, in addition to alum as an effective ingredient. Further, the cosmetic composition may further include a skin absorption enhancer to improve the effects.
  • conventional auxiliary agents such as an antioxidant, a stabilizer, a solubilizing agent, a vitamin, a pigment, and a scent, and a carrier, in addition to alum as an effective ingredient.
  • the cosmetic composition may further include a skin absorption enhancer to improve the effects.
  • the cosmetic composition of the present invention may be prepared as any formulation commonly prepared in the art.
  • the cosmetic composition can be formulated as, for example, a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powdered foundation, an emulsion foundation, a wax foundation, a spray, or the like, but is not limited thereto.
  • the cosmetic composition may be prepared as formulations such as a softening toner, a nutrient toner, a nutrient cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, and a powder.
  • the formulation of the present invention is a paste, a cream or a gel, an animal oil, a vegetable oil, a wax, paraffin, a starch, traganth, a cellulose derivative, a polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, or the like may be used as the carrier ingredient.
  • the formulation of the present invention is a powder or a spray
  • lactose, tal ⁇ silica, aluminum hydroxide, calcium silicate, or polyamide powders may be used as the carrier ingredient, and in particular, if the formulation is a spray, a propellent such as chlorofluorohydrocarbon, propane/butane and dimethyl ether may be included.
  • a solvent, a solubilizing agent or an emulsifier may be used as the carrier ingredient, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or sorbitan fatty add esters.
  • the formulation of the present invention is a suspension
  • a liquid diluent such as water, ethanol and propylene glycol
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, micro- crystalline cellulose, aluminum metahydroxide, bentonite, agar, traganth, or the like may be used as the carrier ingredient.
  • the formulation of the present invention is a surfactant-containing cleanser, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulphosuccinic add monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty add amide ether sulfate, alkylamidobetain, aliphatic alcohol, fatty add glyceride, fatty add di- ethanolamide, vegetable oils, a lanolin derivative or ethoxylated glycerol fatty add ester, or the like may be used as the carrier ingredient.
  • the composition of the present invention may be prepared as a pharmaceutical composition.
  • the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier is generally used in the preparation of formulation, and examples thereof include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acada, caldum phosphate, alginate, gelatin, caldum silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, tal ⁇ magnesium stearate and mineral oil, but are not limited thereto.
  • the pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifier, a suspension agent, a preservative or the like, in addition to the above ingredients.
  • a lubricant e.g., a talc, a kaolin, a kaolin, a kaolin, a kaolin, a kaolin, kaolin, kaolin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, a talct, a talct, a talct, a stevia, glycerin, glycerin, glycerin, a
  • the pharmaceutical composition of the present invention may be administered to mammals such as rat, mouse, livestock, and human via various routes such as oral and parenteral routes (e.g., oral, rectal or intravenous, intramuscular, subcutaneous, in- traepidural or intracerebrovascular injection), preferably transcutaneous route among parenteral routes, and more preferably topical application.
  • oral and parenteral routes e.g., oral, rectal or intravenous, intramuscular, subcutaneous, in- traepidural or intracerebrovascular injection
  • transcutaneous route among parenteral routes preferably topical application.
  • a suitable dosage of the pharmaceutical composition of the present invention may be determined depending on various factors such as formulation methods, administration mode, the patient's age, body weight, gender and health state, diet, administration time, administration routes, excretion rates, and drug sensitivity.
  • the pharmaceutical composition of the present invention may be administered at a daily dosage of 0.001-100 mg/kg one time or several times.
  • the pharmaceutical composition of the present invention may be preferably administered at a daily dosage of 1.0 to 3.0 ml one time or five times for 1 month or more.
  • the scope of the present invention is not intended to be limited by the dosage.
  • the pharmaceutical composition of the present invention may be formulated into a unit dosage form, such as a single-dose dosage form or a multidose container, using the pharmaceutically acceptable carriers and/or exdpients according to the methods known to those skilled in the art.
  • the pharmaceutical composition may be formulated into any suitable formulations including oral formulations such as powder, granules, tablets, capsules, suspensions, emulsions, syrup, and aerosol, topic external preparations such as ointment and cream, suppository or sterilized solution for injection.
  • the pharmaceutical formulations may further include a dispersing agent or a stabilizing agent.
  • the composition of the present invention may be formulated into a food composition.
  • the food composition may include typical ingredients used in the preparation of food, in addition to alum as an effective ingredient.
  • examples thereof include proteins, carbohydrates, lipids, nutrients, seasonings and flavoring agents.
  • carbohydrate include monosaccharides such as glucose and fructose; dis- accharides such as maltose, sucrose, oligosaccharide; and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol.
  • flavoring agent examples include natural flavoring agents such as thaumatin and stevia extract (e.g., levaudioside A, glycyrrhizin or the like) and synthetic flavoring agents such as saccharin and aspartame.
  • natural flavoring agents such as thaumatin and stevia extract (e.g., levaudioside A, glycyrrhizin or the like)
  • synthetic flavoring agents such as saccharin and aspartame.
  • the food composition of the present invention may further include citric acid, high fructose corn syrup, sugar, glucose, acetic add, malic add, fruit juice, a eucommia bark extract, a jujube extract, a licorice extract or the like, in addition to alum.
  • alum was found to be safe for human skin as a natural substance. Accordingly, the alum of the present invention has no toxidty and side effects, thereby being safely used for a long period of time, in particular, applied to cosmetic, pharmaceutical and food compositions.
  • composition of the present invention comprises alum as an effective ingredient
  • the effective ingredient, alum provides an excellent effect of improving wrinkles by molecular mechanism responsible for inhibition of collagenase activity and stimulation of collagen synthesis, a skin whitening effect, an anti-inflammatory effect, an anti-obesity effect, and an excellent effect of stimulating hair growth or preventing hair loss;
  • composition of the present invention exhibits no cytotoxicity and skin complications, thereby being safely applied to cosmetic, pharmaceutical and food compositions.
  • Example 1 Evaluation of wrinkle-improving effect of alum
  • the wrinkle-improving effect can be typically evaluated by analysis of collagen biosynthesis ability, collagenase inhibitory activity, and a clinical test.
  • Human normal fibroblast Pacific Corp., Seoul
  • Human normal fibroblast Pacific Corp., Seoul
  • a DMEM medium (2 x 10 cells/well)
  • the medium was taken out from the well, and it was treated with the composition at varying concentrations, and cultured for 24 hrs.
  • the cell medium was collected to prepare a sample.
  • PICP collagen Type I C-peptide EIA kit
  • Murine B 16 melanoma cells (Korean Cell Line Bank) were used to measure the inhibitory effect of alum on melanin synthesis, which was compared with the inhibitory effect of arbutin on melanin synthesis.
  • Murine melanoma (B- 16 FlO, Korean Cell Line Bank) cells were inoculated on 6- well plates containing DMEM media supplemented with 10% FBS (fetal bovine serum) (1 x 10 cells per well), and cultured in a 5% CO incubator at 37 0 C until reaching about 80% confluency. Then, media was removed from the cells, replaced with diluted fresh media, and cultured in a 5% CO incubator at 37 0 C for 3 days.
  • FBS fetal bovine serum
  • 2 treatment concentration of alum is determined over a range of 1 ppm, 10 ppm and 50 ppm, which show no cytotoxicity.
  • Media was removed from the cells, and the cells were washed with PBS (phosphate buffered saline), followed by trypsin treatment.
  • the cells were recovered, and counted using a hemocytometer (Tiefe Depth Profondeur 0.100 mm, Paul Marienfeld GmbH & Co. KG, Germany). Then, the cells were centrifuged at 5,000 to 10,000 rpm for 10 min, and the supernatant was removed to obtain a pellet.
  • the pellet was dried at 6O 0 C, and suspended in 100 ml of 1 M sodium hydroxide solution containing 10% DMSO in a 6O 0 C water bath to obtain melanin in the cells. Absorbance was determined at 490 nm using a microplate reader (Bio-Tek ELx8O81U, USA) to assess the melanin content per cell. The results are shown in the following Table 4.
  • Murine B 16 melanoma cells (Korean Cell Line Bank) were used to measure the inhibitory effect of alum on tyrosinase activity, which was compared with the inhibitory effect of arbutin on tyrosinase activity.
  • Murine melanoma (B- 16 Fl, Korean Cell Line Bank) cells were inoculated on 6- well plates containing DMEM media supplemented with 10% FBS (fetal bovine serum) (1 x 10 cells per well), and cultured in a 5% CO incubator at 37 0 C until reaching about 80% confluency. Then, media was removed from the cells, replaced with diluted fresh media, and cultured in a 5% CO incubator at 37 0 C for 3 days. The treatment con-
  • Example 5 Evaluation of skin whitening effect in animal [93] Brown guinea pigs (Tortoiseshell guinea pigs), which are known to increase pigmentation upon exposure to UV like human, were used to measure the whitening effect of alum.
  • Example 6 Safety test of alum on human skin
  • Formulations having squalene as a base with addition of alum at 1%, 5%, and 10% were prepared. Each of the formulations was applied in cumulative patches to forearm areas of 30 healthy adults in total 9 times for 24 hours every second day, and it was determined whether alum stimulates the skin or not.
  • a Finn chamber (Epitest Ltd, Republic of Finland) was used. 15 /i6 -portions of the skin external agents were dropped on the chamber, and patches were applied thereon. The response level of the skin per every application was scored using the following Mathematical Equation 2. The results are shown in the following Table 7.
  • Example 7 Evaluation of anti-inflammatory effect
  • a human monocyte cell line THP- 1 (Korean Cell Line Bank) was used to measure the COX inhibitory activity according to a typical method. The measurement of COX activity was performed according to Method in Enzymology 43:9 (1994), published by F. J. Van de Ouderaaa and Muytenhek.
  • the THP-I cell line was cultured, and then the cells were aliquoted in a 24-well plate.
  • the reaction volume is made up to 500 /i2/well, and lipopolysacharide (LPS, 1 ⁇ g/ml, Sigma) and 2 id of each sample compound dissolved in a solvent, shown in the following Table 8, were added to the cells, followed by culturing for 24-48 hrs under the same conditions. After 24-48 hrs, calcium ionophore (Sigma) and 1 ⁇ Jl of Ll-14CJ arachidonic add (in EtOH, 0.1 ⁇ Ci/ ml, Sigma) were added to each well, followed by culturing for 10 min under the same conditions. Then, citric acid was added to each well, and shaken to adjust the pH to 3.5.
  • LPS lipopolysacharide
  • 500 id of each culture solution were taken, and aliquoted to a microcentrifuge tube. Then, 700 id of ethyl acetate was added thereto, followed by shaking for 10 min. 500 id of ethyl acetate layer was taken, and concentrated using a speed vacuum dryer for 20 min. 20 id of the concentrated residue was dissolved in ethyl acetate, and then applied to a TLC plate with authentic standards. Radioactive bands were identified by comparison with authentic eicosanoid standards, and the radioactivity of each band was measured using a BAS 2000 bio-imaging analyzer (Fuji, Japan).
  • Example 8 Anti-obesity effect
  • each sample solution was adjusted so that 0.1 ml of the solution was given per 10 g body weight of animal (1.5 g/kg and 1 g/kg).
  • a 5% lecithin emulsion was administered. After fasting the mice, the sample was administered once by force on the next day. During the test period over 2 weeks, the body weight and general conditions were monitored.
  • the present invention provides a composition comprising alum as an effective ingredient.
  • the effective ingredient, alum used in the composition of the present invention provides an excellent effect of improving wrinkles by molecular mechanism responsible for inhibition of collagenase activity and stimulation of collagen synthesis, a skin whitening effect, an anti-inflammatory effect, an anti-obesity effect, and an excellent effect of stimulating hair growth or preventing hair loss. Further, the composition of the present invention exhibits no cytotoxicity and skin complications, thereby being safely applied to cosmetic, pharmaceutical and food compositions.

Abstract

The present invention relates to a composition for improving wrinkles, whitening skin, inhibiting inflammation and obesity, and stimulating hair growth and preventing hair loss, comprising alum as an effective ingredient. The composition comprising alum can be safely used without skin complications. In addition, the composition of the present invention increases collagen synthesis and inhibits collagenase activity to exhibit an excellent anti-wrinkle effect, and has a skin whitening effect, anti-inflammatory effect, anti-obesity effect, and effects of preventing hair loss and stimulating hair growth. Accordingly, the composition of the present invention is very useful for improving wrinkles, melasma or freckles, whitening skin, inhibiting inflammation and obesity, and preventing hair loss and stimulating hair growth.

Description

Description
COMPOSITIONS FOR IMPROVING SKIN CONDITIONS
COMPRISING ALUM
Technical Field
[1] The present invention relates to a composition for improving skin conditions, and more particularly to a composition for improving skin conditions comprising alum, in which the composition has an excellent product stability, can be safely used without skin complications, and has an excellent anti- wrinkle effect, skin whitening effect, anti-obesity effect, anti-inflammatory effect, and excellent effects of preventing hair loss and stimulating hair growth. Background Art
[2] With the specific characteristics like wrinkles, aged skin is one of the most visible consequences of the aging process. Skin is predisposed to two main aging processes, "intrinsic aging" characterized by changes in the function, structure, or shape of skin associated with age and "photoaging" due to damage caused by UV radiation.
[3] The most significant changes oxur in the dermis, and aged skin exhibits the typical sign of dermal atrophy, which oxurs at the age of 70 or more. Dermal change is generated by the changes in the high molecular- weight components among the extracellular matrix components, due to decrease in the number of fibroblasts and their biosynthetic capability. The specific changes include cleavage of collagen fiber, reduction in mucopolysaccharide synthesis, reduction in the number and diameter of collagen and elastin, breakdown of collagen and elastin, and angiotension. A major factor that affects wrinkle formation is the amount of expression and activity of collagenase, which is a collagen degradation enzyme that reduces collagen synthesis and content, among various factors such as moisture content, collagen content, and immune response against environmental stress. The effect of alum on collagen and collagenase extract has not been reported. However, in experiments described in the present invention, it was found that alum has effects of enhancing collagen synthesis and inhibiting collagenase activity.
[4] Human skin color is determined by the concentration and distribution of melanin in the skin. Melanin synthesized in the epidermal melanocytes is a polymer of polyphenols existing in the form of complexes of dark pigment and protein. It is responsible for protecting the skin against UV radiation. It is known that tyrosinase present in melanocytes is the greatest contributor in melanin biosynthesis. Tyrosinase is a key enzyme in skin pigmentation, and catalyzes the conversion of tyrosine to DOPA and dopaquinone, which are intermediate products formed during melanin biosynthesis.
[5] Environmental pollution and vehicle exhaust gas contribute to hormone imbalance, leading to an increased incidence and earlier age of onset of hair loss. In addition, any abnormality in the functioning of the skin immune system leads to a variety of der- matologic complications, including dermatitis and psoriasis. Further, there has been a significant increase in the prevalence of obesity among children and adolescents due to instant foods and preference for a meat diet.
[6] Accordingly, there is a need to develop a substance capable of effectively solving aesthetic and social problems, such as intrinsic aging, wrinkles, melasma or freckles due to UV, obesity, immune imbalance, and hair loss.
[7] In this regard, the present inventors have made intensive investigation to find a cosmetic material having high safety and stability and excellent efficacy of improving skin conditions. They found that alum has a variety of efficacies such as improvement of wrinkles and enhancement of skin whitening, as well as excellent safety and stability.
Disclosure of Invention Technical Problem
[8] The present inventors have made an effort to develop a novel substance having an excellent anti- wrinkle effect, skin whitening effect, anti-inflammatory effect, anti- obesity effect, and excellent effects of preventing hair loss and stimulating hair growth, and having high stability without skin complications. As a result, they found that a composition comprising alum as an effective ingredient has excellent efficacy and safety to provide an excellent anti- wrinkle effect, skin whitening effect, antiinflammatory effect, and excellent effects of preventing hair loss and stimulating hair growth, thereby completing the present invention. Technical Solution
[9] Accordingly, it is an object of the present invention to provide a composition for improving skin conditions, comprising alum as an effective ingredient.
[10] Further, it is another object of the present invention to provide an anti-obesity composition, comprising alum as an effective ingredient. Best Mode for Carrying Out the Invention
[11] In one aspect, the present invention provides a composition for improving skin conditions comprising alum as an effective ingredient, in which the improvement of skin conditions includes an anti-wrinkle effect, a skin whitening effect, an antiinflammatory effect, and effects of stimulating hair growth and preventing hair loss.
[12] In another aspect, the present invention provides an anti-obesity composition, comprising alum as an effective ingredient.
[13]
[14] The present inventors have made an effort to develop a novel substance having an excellent anti- wrinkle effect, skin whitening effect, anti-inflammatory effect, anti- obesity effect, and excellent effects of preventing hair loss and stimulating hair growth, and having high stability without skin complications. As a result, they found that a composition comprising alum as an effective ingredient has excellent efficacy and safety to provide an excellent anti- wrinkle effect, skin whitening effect, antiinflammatory effect, anti-obesity effect, and excellent effects of preventing hair loss and stimulating hair growth.
[15]
[16] Alum, also called alumen, is a double sulfate of aluminum sulfate and a monovalent metal such as alkali metals
Figure imgf000004_0001
than lithium), thallium, and ammonium. Alum has the typical formula MIA (SO ) -12H O or MI SO -Al (SO ) -24H O, and may be called
1 4 2 2 2 4 2 4 3 2 potassium alum (kalinite; KAl(SO ) -12H O), ammonium alum (chermigite; (NH
4 2 2 4
)A1(SO ) -12H O) or the like according to the monovalent metal ion. In addition,
4 2 2
MIMIII(SO ) -12H O (MIII = Ti, V, Cr, Mn, Fe, Co, Rn, Ir, Ga, In, etc.), substituted
4 2 2 with other trivalent metal ions than aluminum, may also be referred to as alum, and called ammonium-iron alum or rubidium-cobalt alum according to each metal ion. Alum is produced by crystallization from a mixed aqueous solution (1:1) of monovalent metal sulfate and trivalent metal sulfate, and the produced crystalline powder is readily soluble, and more soluble by heating in water. Aluminum sulfate [Al (SO ) -18H O] is prepared from aluminum hydroxide in hot, concentrated sulfuric
2 4 3 2 acid, and industrially obtained from a solution of bauxite or clay dissolved in sulfuric acid. Its aqueous solution is acidic by hydrolysis, and tastes astringent.
[17] Alum is known to show efficacy such as hemostasis, antidiarrhea, detoxification and astriction, and also known to be effective in the improvement of melena, Trichomonal vaginitis, and osmidrosis. In addition, alum is used as an adjuvant, which is co-injected with an antigen to enhance the immune response, and is reported to have effects of soothing skin, preventing dental caries, and improving allergy.
[18] [19] The alum of the present invention has a structure of the following Formula 1.
[20] [Formula 1]
[21] H2 O H 2 O H 2 O
0 " 0 " q+ H2 O H 2 O H 2 O
A l
O = S = O O = S = O H 2 ° H 2 ° l _ l _ K + H2 O H2 O
0 ° H2 O H2 O
[22]
[23] The composition of the present invention has an effect of improving wrinkles. The composition of the present invention exhibits an excellent effect of improving wrinkles by molecular mechanism responsible for inhibition of collagenase activity and stimulation of collagen synthesis, which will be described in detail in the following Examples. The phrase, "effect of improving wrinkles" of the composition of the present invention encompasses typical skin-protecting effects (prevention and removal of wrinkles, inhibition of skin aging or the like).
[24] The composition for improving skin conditions of the present invention also has an excellent skin whitening effect, anti-inflammatory effect, and excellent effects of stimulating hair growth and preventing hair loss. As used herein, the phrase "effect of preventing hair loss" or "effect of stimulating hair growth" is used as the same meaning, and has the same meaning as used in the art.
[25] In addition, as described in the following Examples, the composition of the present invention has an excellent anti-obesity effect.
[26]
[27] In particular, it is apparent to those skilled in the art that the alum of Formula 1 of the present invention includes derivatives that exhibit the effect of improving wrinkles due to stimulation of collagen synthesis and/or inhibition of collagenase (MMP-I) activity, or exhibit a skin whitening effect, or an effect of stimulating hair growth or preventing hair loss, among its derivatives produced by addition or substitution of substituent.
[28]
[29] In a preferred embodiment of the present invention, the effective ingredient, alum is contained in an amount of 0.00001 to 10.0 wt%, more preferably 0.0001 to 10 wt%, and most preferably 0.0001 to 5 wt%, based on the total weight of the composition. If the content is less than 0.00001 wt%, the effect is not sufficient, and if the content is more than 10.0 wt%, the effect is slightly increased, whereas there is a problem in the stability upon formulation.
[30]
[31] According to one preferred embodiment of the present invention, the composition of the present invention is a cosmetic composition.
[32] The cosmetic composition of the present invention may include additives commonly used in cosmetic formulations, for example, conventional auxiliary agents such as an antioxidant, a stabilizer, a solubilizing agent, a vitamin, a pigment, and a scent, and a carrier, in addition to alum as an effective ingredient. Further, the cosmetic composition may further include a skin absorption enhancer to improve the effects.
[33] The cosmetic composition of the present invention may be prepared as any formulation commonly prepared in the art. The cosmetic composition can be formulated as, for example, a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powdered foundation, an emulsion foundation, a wax foundation, a spray, or the like, but is not limited thereto. More specifically, the cosmetic composition may be prepared as formulations such as a softening toner, a nutrient toner, a nutrient cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, and a powder.
[34] If the formulation of the present invention is a paste, a cream or a gel, an animal oil, a vegetable oil, a wax, paraffin, a starch, traganth, a cellulose derivative, a polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, or the like may be used as the carrier ingredient.
[35] If the formulation of the present invention is a powder or a spray, lactose, talς silica, aluminum hydroxide, calcium silicate, or polyamide powders may be used as the carrier ingredient, and in particular, if the formulation is a spray, a propellent such as chlorofluorohydrocarbon, propane/butane and dimethyl ether may be included.
[36] If the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent or an emulsifier may be used as the carrier ingredient, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or sorbitan fatty add esters.
[37] If the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol and propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, micro- crystalline cellulose, aluminum metahydroxide, bentonite, agar, traganth, or the like may be used as the carrier ingredient.
[38] If the formulation of the present invention is a surfactant-containing cleanser, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulphosuccinic add monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty add amide ether sulfate, alkylamidobetain, aliphatic alcohol, fatty add glyceride, fatty add di- ethanolamide, vegetable oils, a lanolin derivative or ethoxylated glycerol fatty add ester, or the like may be used as the carrier ingredient.
[39]
[40] According to one preferred embodiment of the present invention, the composition of the present invention may be prepared as a pharmaceutical composition.
[41] If the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is generally used in the preparation of formulation, and examples thereof include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acada, caldum phosphate, alginate, gelatin, caldum silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talς magnesium stearate and mineral oil, but are not limited thereto. The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifier, a suspension agent, a preservative or the like, in addition to the above ingredients. Suitable pharmaceutical carriers and formulations are described in Remington's Pharmaceutical Sciences (19th ed., 1995).
[42] The pharmaceutical composition of the present invention may be administered to mammals such as rat, mouse, livestock, and human via various routes such as oral and parenteral routes (e.g., oral, rectal or intravenous, intramuscular, subcutaneous, in- traepidural or intracerebrovascular injection), preferably transcutaneous route among parenteral routes, and more preferably topical application.
[43] A suitable dosage of the pharmaceutical composition of the present invention may be determined depending on various factors such as formulation methods, administration mode, the patient's age, body weight, gender and health state, diet, administration time, administration routes, excretion rates, and drug sensitivity. For oral administration, the pharmaceutical composition of the present invention may be administered at a daily dosage of 0.001-100 mg/kg one time or several times. Further, for topical administration, the pharmaceutical composition of the present invention may be preferably administered at a daily dosage of 1.0 to 3.0 ml one time or five times for 1 month or more. However, the scope of the present invention is not intended to be limited by the dosage.
[44] The pharmaceutical composition of the present invention may be formulated into a unit dosage form, such as a single-dose dosage form or a multidose container, using the pharmaceutically acceptable carriers and/or exdpients according to the methods known to those skilled in the art. The pharmaceutical composition may be formulated into any suitable formulations including oral formulations such as powder, granules, tablets, capsules, suspensions, emulsions, syrup, and aerosol, topic external preparations such as ointment and cream, suppository or sterilized solution for injection. The pharmaceutical formulations may further include a dispersing agent or a stabilizing agent.
[45]
[46] According to one preferred embodiment of the present invention, the composition of the present invention may be formulated into a food composition.
[47] If the composition of the present invention is formulated into a food composition, the food composition may include typical ingredients used in the preparation of food, in addition to alum as an effective ingredient. Examples thereof include proteins, carbohydrates, lipids, nutrients, seasonings and flavoring agents. Examples of the above mentioned carbohydrate include monosaccharides such as glucose and fructose; dis- accharides such as maltose, sucrose, oligosaccharide; and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of the flavoring agent include natural flavoring agents such as thaumatin and stevia extract (e.g., levaudioside A, glycyrrhizin or the like) and synthetic flavoring agents such as saccharin and aspartame.
[48] If the food composition of the present invention is prepared as a drink, the food composition may further include citric acid, high fructose corn syrup, sugar, glucose, acetic add, malic add, fruit juice, a eucommia bark extract, a jujube extract, a licorice extract or the like, in addition to alum.
[49]
[50] On the other hand, as a result of cumulative irritation test in a spedfic Example of the present invention, alum was found to be safe for human skin as a natural substance. Accordingly, the alum of the present invention has no toxidty and side effects, thereby being safely used for a long period of time, in particular, applied to cosmetic, pharmaceutical and food compositions.
[51] [52] Characteristics and advantages of the present invention can be summarized as follows:
[53] (i) the composition of the present invention comprises alum as an effective ingredient;
[54] (ii) the effective ingredient, alum provides an excellent effect of improving wrinkles by molecular mechanism responsible for inhibition of collagenase activity and stimulation of collagen synthesis, a skin whitening effect, an anti-inflammatory effect, an anti-obesity effect, and an excellent effect of stimulating hair growth or preventing hair loss; and
[55] (iii) the composition of the present invention exhibits no cytotoxicity and skin complications, thereby being safely applied to cosmetic, pharmaceutical and food compositions.
[56]
Mode for the Invention
[57] Hereinbelow, the present invention will be described in more detail with reference to
Examples. However, these Examples are for illustrative purposes only, and it will be understood by those skilled in the art that the present invention is not limited thereto.
[58]
[59] Example 1: Evaluation of wrinkle-improving effect of alum
[60] The wrinkle-improving effect can be typically evaluated by analysis of collagen biosynthesis ability, collagenase inhibitory activity, and a clinical test. Human normal fibroblast (Pacific Corp., Seoul) was inoculated in each well of a 6-well microplate containing a DMEM medium (2 x 10 cells/well), and cultured at a 5%-CO incubator at 370C for 24 hours. After 24 hrs, the medium was taken out from the well, and it was treated with the composition at varying concentrations, and cultured for 24 hrs. After 24 hrs, the cell medium was collected to prepare a sample.
[61] For the amount of collagen synthesis, the amount of procollagen type I C-peptide
(PICP) was measured using a collagen measuring kit (Procollagen Type I C-peptide EIA kit (MKlOl), Takara, Kyoto, Japan), as detailed in the manufacturer's instructions (Takara).
[62] For the method for measuring the activity level of a collagen decomposing enzyme, collagenase, an antibody against collagenase was used. In this test, the cells were treated with phorbol myristate acetate (PMA) (Sigma), which is a collagenase inducing agent. The procedure was performed according to the manufacturer's protocol. A Type I Collagenase assay kit (Amersham Biosdences, RPN2629) was used, and an absorbance was measured with an ELISA reader (Bio-Tek ELx8O8™ Series Ultra Microplate Reader, England). The determined standard value was expressed in mean standard variation, and a statistical significance was assayed with a t-test using a SPSS/PC+ program. The results are shown in the following Table 1.
[63] Table 1 [Table 1] [Table ]
Figure imgf000010_0001
[64] [65] As shown in Table 1, it was found that alum promoted collagen synthesis and inhibited collagenase activity, indicating that alum has an effect of improving wrinkles. In addition, the increased rate of collagen synthesis and inhibition rate of collagenase were increased, as the treatment concentration of alum was increased.
[66] [67] Example 2: Evaluation of wrinkle-improving effect of cosmetic containing alum
[68] The effect of improving wrinkles of a cosmetic containing alum was measured by a clinical test. The nutrient creams of Preparative Example A (nutrient creams having alum at 1%, 2% and 5%) and of Comparative Preparative Example (nutrient cream containing purified water) were used.
[69] The effect of improving wrinkles was evaluated by measuring the changes in skin resilience. Measurement on skin resilience was made at a temperature of 24 to 260C, and a humidity maintained at 38 to 40%, with 30 healthy women (25 to 35-year-old) as the subjects to be tested, by applying three kinds of the nutrient creams of Preparative Example A, and the nutrient cream of Comparative Preparative Example on the face of the subject twice per day for 3 months, and then measuring the skin resilience using Cutometer SEM 474 (Courage+Khazaka, Cologne, Germany). The evaluation standards were relatively set as follows: Score 0: No skin resilience through Score, 5: A lot skin resilience. The results are shown in the following Table 2. [70] Table 2 [Table 2] [Table ]
Figure imgf000011_0001
[71] [72] As shown in Table 2, it was found that the cream containing alum of Preparative Example A of the present invention was better in the effect of improving skin wrinkles, as compared with the cream of Comparative Preparative Example, and skin resilience was improved as the concentration of alum is increased.
[73] [74] Preparative Example A. Preparation of cream containingalum [75] The ingredients and the contents of a nutrient cream containing alum are as shown in the following Table 3. Purified water, triethanol amine, and propylene glycol in an aqueous phase were heated to 7O0C for dissolution, and fatty acids, oily ingredients, an emulsifier and a preservative in an oily phase were heated to 7O0C for dissolution. Then, both of the obtained solutions were combined for emulsification. After completion of the emulsification, the solution was cooled to 450C. Then, the alum and a flavor were added thereto, dispersed, and then cooled to 3O0C.
[76] Table 3
[Table 3]
[Table ]
Ingredients and contents of nutrient cream containing alum
Figure imgf000012_0001
[77] [78] Example 3: Evaluation of inhibitory effect of alum on melanin synthesis
[79] Murine B 16 melanoma cells (Korean Cell Line Bank) were used to measure the inhibitory effect of alum on melanin synthesis, which was compared with the inhibitory effect of arbutin on melanin synthesis.
[80] Murine melanoma (B- 16 FlO, Korean Cell Line Bank) cells were inoculated on 6- well plates containing DMEM media supplemented with 10% FBS (fetal bovine serum) (1 x 10 cells per well), and cultured in a 5% CO incubator at 370C until reaching about 80% confluency. Then, media was removed from the cells, replaced with diluted fresh media, and cultured in a 5% CO incubator at 370C for 3 days. The
2 treatment concentration of alum is determined over a range of 1 ppm, 10 ppm and 50 ppm, which show no cytotoxicity. Media was removed from the cells, and the cells were washed with PBS (phosphate buffered saline), followed by trypsin treatment. The cells were recovered, and counted using a hemocytometer (Tiefe Depth Profondeur 0.100 mm, Paul Marienfeld GmbH & Co. KG, Germany). Then, the cells were centrifuged at 5,000 to 10,000 rpm for 10 min, and the supernatant was removed to obtain a pellet. The pellet was dried at 6O0C, and suspended in 100 ml of 1 M sodium hydroxide solution containing 10% DMSO in a 6O0C water bath to obtain melanin in the cells. Absorbance was determined at 490 nm using a microplate reader (Bio-Tek ELx8O81U, USA) to assess the melanin content per cell. The results are shown in the following Table 4.
[81] Table 4 [Table 4] [Table ]
Figure imgf000013_0001
[82] [83] As shown Table 4, alum exhibited higher inhibition rate of melanin synthesis than arbutin. In addition, it can be seen that the inhibition rate of melanin synthesis was increased in a concentration-dependent manner.
[84] [85] Example 4: Evaluation of inhibitory effect of alum on tyrosinase activity
[86] Murine B 16 melanoma cells (Korean Cell Line Bank) were used to measure the inhibitory effect of alum on tyrosinase activity, which was compared with the inhibitory effect of arbutin on tyrosinase activity.
[87] Murine melanoma (B- 16 Fl, Korean Cell Line Bank) cells were inoculated on 6- well plates containing DMEM media supplemented with 10% FBS (fetal bovine serum) (1 x 10 cells per well), and cultured in a 5% CO incubator at 370C until reaching about 80% confluency. Then, media was removed from the cells, replaced with diluted fresh media, and cultured in a 5% CO incubator at 370C for 3 days. The treatment con-
2 centration of alum is determined over a range of 1 ppm, 10 ppm and 50 ppm, which show no cytotoxicity. Media was removed from the cells, and the cells were washed with PBS (phosphate buffered saline), followed by trypsin treatment. The cells were recovered, and counted using a hemocytometer (Tiefe Depth Profondeur 0.100mm, Paul Marienfeld GmbH & Co. KG, Germany). Then, the cells were centrifuged at 5,000 to 10,000 rpm for 10 min, and the supernatant was removed to obtain a pellet. The pellet was resuspended using a lysis buffer, and centrifuged at 12,000 rpm for 10 min to collect the supernatant. Absorbance was determined at 492 nm using a microplate reader (Bio-Tek ELx8O81U, USA) to assess the tyrosinase activity per cell. The results are shown in the following Table 5.
[88] Table 5 [Table 5] [Table ]
Figure imgf000014_0001
[89] [90] As shown Table 5, it can be seen that alum exhibited higher inhibition rate of tyrosinase activity than arbutin. In addition, it can be seen that the inhibition rate of tyrosinase activity was increased in a concentration-dependent manner.
[91] [92] Example 5: Evaluation of skin whitening effect in animal [93] Brown guinea pigs (Tortoiseshell guinea pigs), which are known to increase pigmentation upon exposure to UV like human, were used to measure the whitening effect of alum.
[94] To cause pigmentation in the brown guinea pig by UV, light- shielding aluminum foil
2 with windows of 3x3 cm was adhered to hair-removed abdominal skin of brown guinea pig, and then UV light was irradiated thereon with a SE lamp Wavelength
2
290-320 nm, Toshiba) (total irradiation energy = 1350 mJ/cm ). After UV irradiation, the aluminum foil was removed, and then the samples (alum and arbutin) were applied as follows. Increased pigmentation was observed at 2 or 3 days after UV irradiation, and reached a maximum after about 2 weeks. From the maximum, each sample was applied.
[95] Applications were performed once or twice a day for 50 days. The samples were dissolved and diluted in a certain solvent (a mixed solvent of propylene glycol: ethanol: water=5 : 3: 2) and applied with a swab. Another region was applied with the solvent only as a control. Occurrence of cumulative irritation also was examined.
[96] The degree of skin pigmentation was determined using a chromameter (CR2002 chromameter, Minolta, Japan) to evaluate the effects. The results are shown in the
* * * * following Table 6. L A B colorimetric system is used to classify color, and an L value was used as standard in the present invention. The L value was corrected using white board standard, and measured more than five times at one region, repeatedly. Pigmentation was evenly distributed. Skin color differences (ΔL ) between initial application point and terminal application point were obtained by using the following Mathematical Equation 1, and then using these values, their effects of the applied samples were evaluated. The results are shown in the following Table 6.
[97]
[98] [Mathematical Equation 1]
[99] ΔL = (L value at 00 days after application) - (L value at initial application day)
[100]
[101] ΔL values were obtained at sample application region and control application region and compared. From the result, the skin whitening effects of the samples can be evaluated.
[102] Table 6 [Table 6] [Table ]
Figure imgf000015_0001
[103] [104] As shown Table 6, it was found that alum exhibited better skin whitening effect than arbutin. Further, in the cumulative irritation test, alum causes no cumulative irritation. Therefore, it can be seen that alum is safe for skin.
[105]
[106] Example 6: Safety test of alum on human skin
[107] In order to confirm the safety of alum on the human skin, an experiment to rectify skin safety was carried out. As the test method, a skin cumulative stimulation test was carried out.
[108] Formulations having squalene as a base with addition of alum at 1%, 5%, and 10% were prepared. Each of the formulations was applied in cumulative patches to forearm areas of 30 healthy adults in total 9 times for 24 hours every second day, and it was determined whether alum stimulates the skin or not. For the method for applying the patches, a Finn chamber (Epitest Ltd, Republic of Finland) was used. 15 /i6 -portions of the skin external agents were dropped on the chamber, and patches were applied thereon. The response level of the skin per every application was scored using the following Mathematical Equation 2. The results are shown in the following Table 7.
[109]
[110] [Mathematical Equation 2]
[111] Average response degree =
[112] [[{ (Response index x Response degree) / Total number of subjects } xHighest score (4 points)] x 100] ÷ Times of examination (9 rounds)
[113]
[114] In regard to the response degree, 1 point was provided for ±, 2 points for +, 4 points for ++. When the average response degree was less than 3, the composition was determined to be safe for the skin.
[115] Table 7
[Table 7] [Table ]
Figure imgf000017_0001
[116] [117] As shown in Table 7, in Experimental groups 1, 2, and 3, the subjects corresponding to ±, + and ++ numbered 0, 0 and 1, and the average response degree was 0.00, 0.00, and 0.09, respectively. Consequently, the average response degree was less than 3, demonstrating that alum causes no noticeable cumulative irritation to be safe for human skin.
[118] [119] Example 7: Evaluation of anti-inflammatory effect [120] In order to confirm the anti-inflammatory effect, a human monocyte cell line, THP- 1 (Korean Cell Line Bank) was used to measure the COX inhibitory activity according to a typical method. The measurement of COX activity was performed according to Method in Enzymology 43:9 (1994), published by F. J. Van de Ouderaaa and Muytenhek. For the COX assay, the THP-I cell line was cultured, and then the cells were aliquoted in a 24-well plate. The reaction volume is made up to 500 /i2/well, and lipopolysacharide (LPS, 1 μg/ml, Sigma) and 2 id of each sample compound dissolved in a solvent, shown in the following Table 8, were added to the cells, followed by culturing for 24-48 hrs under the same conditions. After 24-48 hrs, calcium ionophore (Sigma) and 1 μJl of Ll-14CJ arachidonic add (in EtOH, 0.1 μCi/ ml, Sigma) were added to each well, followed by culturing for 10 min under the same conditions. Then, citric acid was added to each well, and shaken to adjust the pH to 3.5. 500 id of each culture solution were taken, and aliquoted to a microcentrifuge tube. Then, 700 id of ethyl acetate was added thereto, followed by shaking for 10 min. 500 id of ethyl acetate layer was taken, and concentrated using a speed vacuum dryer for 20 min. 20 id of the concentrated residue was dissolved in ethyl acetate, and then applied to a TLC plate with authentic standards. Radioactive bands were identified by comparison with authentic eicosanoid standards, and the radioactivity of each band was measured using a BAS 2000 bio-imaging analyzer (Fuji, Japan).
[121] Table 8 [Table 8] [Table ]
Figure imgf000018_0001
[122] [123] As shown in Table 8, alum was found to effectively inhibit the COX activity. Consequently, it can be seen that alum exhibits anti-inflammatory effect.
[124] [125] Example 8: Anti-obesity effect [126] To examine the anti-obesity effect, the following experiment was performed using a well known animal. The results are shown in the following Table 9.
[127] The measurement of anti-obesity effect was performed as follows: [128] Crj: ICR male mice (Charles River, Japan) aged 7 weeks were preliminarily fed for 1 week, and then divided into groups each having 7 animals and subjected to the test. The animals were fed in a thermo-hygrostat at a temperature of 23 ± I0C and a humidity of 55 ± 5% under illumination for 12 hours per day. They were fed with a feed Labo MR (manufactured by Nippon Nosan) and allowed to take water ad libitum. Alum (0.1% and 1%) was prepared in the form of liposome (dissolved in 5% lecithin). The concentration of each sample solution was adjusted so that 0.1 ml of the solution was given per 10 g body weight of animal (1.5 g/kg and 1 g/kg). To a control group, a 5% lecithin emulsion was administered. After fasting the mice, the sample was administered once by force on the next day. During the test period over 2 weeks, the body weight and general conditions were monitored.
[129] Table 9 [Table 9] [Table ]
Figure imgf000019_0001
[130] [131] As shown in Table 9, alum was found to exhibit the anti-obesity effect. The effect was increased, as the treatment concentration was increased.
[132] [133] Example 9: Effects of preventing hair loss and stimulating hair growth
[134] To examine the effects of preventing hair loss and stimulating hair growth, the sample was prepared in a hydrogel base containing only the preservative and thickening agent. The external preparation for stimulating hair growth (3 cc) was applied to 10 patients with alopecia, caused by chemotherapy or radiation, twice a day for 6 months. As a result, excellent effects including hair root formation were observed in 8 patients of them. The results are shown in the following Table 10. As a control, moxidil (available from Hanmi Pharmaceutical Co., Ltd.) was used.
[135] Table 10 [Table 10] [Table ]
Figure imgf000020_0001
[136] [137] As shown in Table 10, it was found that the alum of the present invention exhibited the effect of stimulating hair growth, similar to that of moxidil, which is a commercially available product for promoting hair growth.
[138]
Industrial Applicability
[139] The present invention provides a composition comprising alum as an effective ingredient. The effective ingredient, alum used in the composition of the present invention provides an excellent effect of improving wrinkles by molecular mechanism responsible for inhibition of collagenase activity and stimulation of collagen synthesis, a skin whitening effect, an anti-inflammatory effect, an anti-obesity effect, and an excellent effect of stimulating hair growth or preventing hair loss. Further, the composition of the present invention exhibits no cytotoxicity and skin complications, thereby being safely applied to cosmetic, pharmaceutical and food compositions.

Claims

Claims
[1] A composition for improving skin conditions, comprising alum as an effective ingredient, wherein the composition is used for improving wrinkles.
[2] A composition for improving skin conditions, comprising alum as an effective ingredient, wherein the composition is used for whitening skin.
[3] A composition for improving skin conditions, comprising alum as an effective ingredient, wherein the composition is used for stimulating hair growth or preventing hair loss.
[4] A composition for improving skin conditions, comprising alum as an effective ingredient, wherein the composition is used for inhibiting inflammation.
[5] An anti-obesity composition comprising alum as an effective ingredient.
[6] The composition according to any one of claims 1 to 5, wherein the alum is contained in an amount of 0.0001 to 10.0 wt%, based on the total weight of composition.
[7] The composition according to any one of claims 1 to 5, wherein the composition is a cosmetic composition.
[8] The composition according to claim 7, wherein the composition has a formulation selected from the group consisting of a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant- containing cleanser, an oil, a powdered foundation, an emulsion foundation, a wax foundation, and a spray.
[9] The composition according to any one of claims 1 to 5, wherein the composition is a pharmaceutical composition.
[10] The composition according to any one of claims 1 to 5, wherein the composition is a food composition.
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FR2966722A1 (en) * 2010-10-27 2012-05-04 Oreal Composition, useful for the cosmetic and non-therapeutic treatment of skin, comprises, in an aqueous medium, alum, porous particles, and at least one salicylic acid compound and its derivatives
GB2516409A (en) * 2012-04-19 2015-01-28 Wisam Fouad Al-Badri Babylon gel
EP3403673A4 (en) * 2016-01-12 2019-12-11 National University Corporation Tokyo Medical and Dental University Composition for preventing or ameliorating loss of hair and graying of hair, and use thereof

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GB2516409A (en) * 2012-04-19 2015-01-28 Wisam Fouad Al-Badri Babylon gel
EP3403673A4 (en) * 2016-01-12 2019-12-11 National University Corporation Tokyo Medical and Dental University Composition for preventing or ameliorating loss of hair and graying of hair, and use thereof
US10702544B2 (en) 2016-01-12 2020-07-07 National University Corporation Tokyo Medical And Dental University Composition for ameliorating loss of hair and graying of hair, and use thereof
JP2021176876A (en) * 2016-01-12 2021-11-11 国立大学法人 東京医科歯科大学 Composition for suppressing or ameliorating hair loss and whitening and use thereof
US11298372B2 (en) 2016-01-12 2022-04-12 National University Corporation Tokyo Medical And Dental University Composition for ameliorating loss of hair and graying of hair, and use thereof

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