KR20140057806A - Composition for wound repair and accelerating skin-regeneration comprising beta-lapachone or pharmaceutically acceptable salts - Google Patents

Abstract

The present invention relates to a composition comprising beta-lapachone or a pharmaceutically acceptable salt thereof as an active ingredient for treating wound and promoting skin regeneration and, more specifically, to pharmaceutical products with various formulations for external use, and cosmetic products which have effects of promoting cell proliferation, cell migration, and skin regeneration, and activating TGF-beta receptors by comprising beta-lapachone or a pharmaceutically acceptable salt thereof as an active ingredient.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for promoting wound healing and skin regeneration comprising beta-rapacon or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention And a pharmaceutical composition and cosmetic composition for promoting wound healing and skin regeneration including beta-rapacon.

Because human skin is capable of natural reproduction, some wounds and damage heal the skin itself. However, it is damaged by various causes such as malnutrition, drugs, sunlight, smoking, hypoxia, and the ability to heal or regenerate such damaged skin gradually decreases (Clin Platic surg 2003; 30: 47-56). In particular, skin's healing rate is known to be an indicator of the biological age of the skin, as it slows down as the aging progresses (Biogerontology 2011; 12 (6): 591-7).

Recently, interest in stem cells has been increasing as a technology related to skin regeneration. The biological effects of adipose-derived stem cells are due to the pharmacological action of more than 100 cytokines secreted by these cells (The New England Journal of Medicine 1999; 341 (10): 738-746). It has been shown that TGF-? I (a transforming growth factor) among various cytokines directly acts on the whitening action. TGF-β1 is effective in reducing the number and activity of tyrosinase enzymes and TRP (tyrosinase-related protein) components involved in melanin production, thereby reducing melanin production, thereby reducing spiny, freckles or dullness. In addition, more than 100 cytokines such as PDGF (platelet factor), FGF (dermal cell growth factor), and VEGF (vascular endothelial growth factor) have been successfully used for new cell proliferation, It can be effectively used for scarring and wrinkle improvement.

For example, autologous blood skin rejuvenation, known as PRP (Platelet-rich plasma) injection, can be used to remove the growth factors involved in skin regeneration (PDGF, FGF, EGF, VEGF, TGF- It is known that stem cells are activated by these growth factors and differentiated to fit the tissues to help regenerate the skin.

In addition, according to the patent, a growth factor or a mimic peptide is applied for the greatest effect of wound healing and skin regeneration (Korean patent application 10-2010-7014945, 10-2008-0033687, 10-2008-7018163) . However, these growth factors or replication peptides have low stability and skin permeation efficiency, and have a high manufacturing cost. Therefore, it is necessary to apply stable and effective active ingredients that activate the signal transduction pathway of TGF-beta, an effective growth factor for wound healing and skin regeneration.

On the other hand, beta-lapachol is a natural quinone substance obtained from lapacho tree ( Tabebuia avellandedae), which is extracted from various plants.

Through prior studies of beta-Rapa cone anticancer effect [Terai, Kaoru et al, Cisplatin enhances the anticancer effect of beta-lapachone by upregulating NQO1, Anticancer Drugs, Nov, 01; 20 (10): 901-9 (2009.. ); Anti-tumor effects [HR Shah et al ., Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell linesBeta & lt ; RTI ID = 0.0 > -lapachone in retinoblastoma cell lines , Eye 22, 454-460 (March 2008); U.S. Patent Application Publication No. 2009/0226395, No. 7,070,797], anti-inflammatory effect [Dong-Oh Moon et al ., Anti - inflammatory effects of β- lapachone in lipopolysaccharide - stimulated BV2 microglia, International Immunopharmacology, Vol 7, Issue 4, 506-514, (April 2007)], anti-fungal effect [Shing-Hwa Liu et al. , Inhibition of inducible nitric oxide synthase by β-lapachone in rat alveolar macrophages and aorta, Br J Pharmacol . 126 (3): 746-50. (February 1999)].

However, no research has been conducted on the effect of beta-rapacon, the active ingredient of the present invention, on wound healing and skin regeneration promotion.

U.S. Patent No. 7,074,824 U.S. Patent No. 6,962,944 U.S. Patent No. 6,664,288 U.S. Patent No. 7,361,691 International Patent Publication No. WO 2003/11224 U.S. Patent Application Publication No. 2009/0226395 U.S. Patent No. 7,070,797

Terai, Kaoru et al., Cisplatin enhances the anticancer effect of beta-lapachone by upregulating NQO1., Anticancer Drugs, Nov, 01; 20 (10): 901-9 (2009) H R Shah et al., Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell linesBeta-lapachone in retinoblastoma cell lines, Eye 22, 454-460 (March 2008) Lipopolysaccharide-stimulated BV2 microglia, International Immunopharmacology, Vol 7, Issue 4, 506-514, (April 2007) Shing-Hwa Liu et al., Inhibition of inducible nitric oxide synthase by β-lapachone in rat alveolar macrophages and aorta, Br J Pharmacol. 126 (3): 746-50. (February 1999)

The inventors of the present invention have completed the present invention by confirming that when beta-rapacon is actually applied to the skin, it activates TGF-beta receptor, promotes cell proliferation and cell migration, and exhibits skin regeneration effect.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for promoting wound healing and skin regeneration comprising beta-raffone as an active ingredient.

It is another object of the present invention to provide a cosmetic composition for promoting wound healing and skin regeneration comprising beta-raffone as an active ingredient.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for promoting wound healing and skin regeneration comprising beta-raffone or a pharmaceutically acceptable salt thereof as an active ingredient:

The present invention also provides a cosmetic composition for promoting wound healing and skin regeneration, which comprises beta-raffone, or a pharmaceutically acceptable salt thereof, represented by Formula 1, as an active ingredient.

The composition according to the present invention activates TFG-β receptors, promotes cell proliferation and cell migration, and has a skin regenerating effect, so that it can be applied to various pharmaceutical external preparations and cosmetic products.

1 is an electrophoresis image showing the degree of Smad 2/3 phosphorylation inhibition of fibroblasts treated with beta-rapacon, TGF-beta, and SB431542.
FIG. 2 is a graph showing the cell proliferating ability according to the concentration of beta-raffoncon. FIG.
FIG. 3 is a photograph showing the cell migration according to the concentration of the negative control group and the beta-rapacon.
FIG. 4 is a photograph showing skin conditions before and after using beta-raffon cream and placebo cream, respectively.

The beta-raffone conferred by the present invention is 3,4-dihydro-2,2-dimethyl-2H-naphtho (1,2-b) pyran-5,6- 4-Dihydro-2,2-dimethyl-2H-naphtho (1,2-b) pyran-5,6-

[Chemical Formula 1]

The beta-rapacon is a known substance having a CAS No. 1707-32-8, which can be extracted from natural plants or purchased commercially.

Beta extracted from natural plant-Rapa cone bignoniaceae (Bignoniaceae), verbenaceae (Verbenaceae), proteaceae (Proteaceae), leguminous (Lequminosae), sandpaper tagwa (Sapotaceae), Scrophulariaceae (Scrophulariaceae), Malvaceae (Malvaceae), etc. Of the plant.

For example, it can be produced by a conventional method known in the art, that is, a conventional method such as hot water extraction, room temperature extraction, warming extraction, ultrasonic extraction, supercritical extraction and the like using a conventional solvent.

Preferably a solvent selected from the group consisting of water, ethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin, methanol, ethanol, propanol, isopropanol, butanol and mixtures thereof. Most preferably, 1,3-butylene glycol is used as an extraction solvent and extracted with a sonicator at room temperature for 1 to 12 hours. The time of the ultrasonic extraction may be varied depending on the amount of the sample to be extracted, and the result of the extraction may be filtered or purified.

In the case of commercially available beta-rapacon, it is used after refining. The purification method used at this time can be a method commonly used in this field. Liquid chromatography using various organic solvents, column chromatography using various synthetic resins such as silica gel and activated alumina, and high performance liquid chromatography (HPLC), and the method is not limited to the above purification method .

In order to examine the effect of TGF-beta receptor activation of beta-rapacon in Experimental Example 1 according to the present invention, beta-lapachone and Smad 2/3, as well as SB431542, It was confirmed that TGF-β receptor activation was inhibited by inhibiting phosphorylation.

In addition, as shown in FIG. 2, the cell proliferation promoting effect was measured in Experimental Example 2. As shown in FIG. 2, the cell proliferation was stimulated in a concentration-dependent manner by adding beta-raffone according to the present invention. Of the cells.

As shown in FIG. 3, in the cells treated with beta-raffone at a concentration of 0.05 ug / mL and 0.1 ug / mL, cell proliferation of the wound edge was observed And the movement of the wound was healed by the movement, and the cell migration ability was increased by 17% and 27%, respectively.

In addition, in order to confirm the skin regeneration effect of Beta-Rapacon in Experimental Example 4, human clinical studies were conducted after preparation of cream formulations. As a result, as shown in Fig. 4, And the exfoliation improving effect was excellent.

These results indicate that beta-raffone conceived in the present invention can be applied as a pharmaceutical composition and a cosmetic composition, and when applied to skin, it can heal injured or damaged skin and promote skin regeneration.

Therefore, a composition comprising beta-raffone or a pharmaceutically acceptable salt thereof as an active ingredient can be formulated into a pharmaceutical composition for promoting wound healing and skin regeneration, or a cosmetic composition for promoting wound healing and skin regeneration.

When formulated into a pharmaceutical composition, the composition of the present invention can be formulated by a known method in the pharmaceutical field and mixed with a pharmaceutically acceptable carrier, excipient or the like to prepare a conventional pharmaceutical preparation, for example, , Capsules, granules, powders, ointments, emulsions, gels, creams, and the like, and they can be administered by various routes. Preferably, it may be formulated into a liquid, cream, paste, or solid form for transdermal administration such as a solution for external use, an emulsion, and an ointment.

The beta-raffone according to the present invention can be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include those derived from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, and aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates, Dioleate, aromatic acid, aliphatic and aromatic sulfonic acids. Such pharmaceutically innocuous salts include, but are not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate chloride, bromide, Butyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, succinate, maleic anhydride, maleic anhydride, , Sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzene sulfonate, toluene sulfonate, chlorobenzene sulfide Propyl sulphonate, naphthalene-1-yne, xylenesulfonate, phenylsulfate, phenylbutyrate, citrate, lactate,? -Hydroxybutyrate, glycolate, maleate, Sulfonate, naphthalene-2-sulfonate or mandelate.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or an alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is preferable for the metal salt to produce sodium, potassium or calcium salt. The corresponding silver salt is also obtained by reacting an alkali metal or alkaline earth metal salt with a suitable salt (such as silver nitrate).

In addition, the beta-rapacon according to the present invention may include not only pharmaceutically acceptable salts, but also possible solvates, hydrates and the like which can be prepared therefrom.

The pharmaceutical composition of the present invention contains 0.001 to 10% by weight of the above-mentioned beta-rapacon, or a pharmaceutically acceptable salt thereof, in the whole pharmaceutical composition. The pharmaceutical composition thus prepared is used at an effective dose of 0.00001 mg / kg to 400 mg / kg per dose, and the actual dose of the active ingredient is determined according to the severity of symptoms, the route of administration selected, the age, sex, And the like, and the like. Accordingly, the above dose is not intended to limit the scope of the present invention in any way. The administration can be administered once to several times a day.

When formulated into a cosmetic composition, the content of beta-rapacon is 0.0001 to 10% by weight, preferably 0.01 to 5.0% by weight based on the total weight of the cosmetic composition. The content of beta-rapacon is preferably at least the above-mentioned minimum value so as to attain the effect of improving the minimum wounds and promoting skin regeneration. In view of the deterioration of feeling due to the excessive addition and the possibility of application to various formulations, The content of cone is preferably equal to or less than the maximum value. At this time, it is preferable that the content of beta-rapacon is appropriately adjusted within the above-described range according to the content of the components contained in the formulation or cosmetic composition.

The ingredients contained in the cosmetic composition of the present invention include components commonly used in cosmetic compositions in addition to beta-raffone as an active ingredient, and include conventional additives such as antioxidants, stabilizers, solubilizers, vitamins, , And a carrier.

The composition of the present invention can be prepared in any formulations conventionally produced in the art, and can be used in various forms such as softening agents, convergent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, A cleansing foam, a cleansing water, a pack, a gel, a powder, a body lotion, a body cream, a body oil, a body essence and the like.

When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

In the case where 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 as a carrier component. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include 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.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided to further understand the present invention, and the present invention is not limited by the examples.

Experimental Example  One: TGF -b receptor activation

In order to examine the effect of TGF-beta receptor activation of beta-rapacon according to the present invention, beta-rapacon was purchased from Sigma-Aldrich (USA).

Human normal fibroblasts were inoculated (1 x 10 ⁶ cells / well) into a 60 x 15 mm dish containing DMEM medium containing 10% fetal bovine serum and incubated with 5% CO ₂ CO _{2 2} incubator at 37 < 0 > C for 24 hours. Normal human fibroblasts were purchased from Cascade (USA). The cells were cultured for 5 min in DMEM without serum containing appropriate concentrations of beta-rapacon, TGF-beta and TGF-beta I kinase inhibitor (SB431542). Cells were pulverized with RIPA buffer and 50 ug of the resulting protein was electrophoresed on 8-10% SDS-polyacrylamide gel. Protein was transferred to PVDF membrane and reacted with antibodies of phospho-smad 2, phosphor-smad 3, smad-2, smad-3 (Cell signaling Techonolgy, USA), collagen type I and β-actin (Canta cruz, USA) . The membrane was washed and reacted with horseradish peroxidase-conjugated anti-rabbit IgG antibody (Cell signaling Te4chnology, USA), and the membrane reacted with the substrate was sensitized to X-ray film.

1 is an electrophoresis image showing the degree of Smad 2/3 phosphorylation inhibition of fibroblasts treated with beta-rapacon, TGF-beta, and SB431542. As shown in Fig. 1, SB431542 inhibited the phosphorylation of Smad2 / 3 by TGF-beta receptor stimulation and beta-raffone addition also inhibited Smad 2/3 phosphorylation. Therefore, it was found that the beta-rapacon of the present invention had an effect of activating TGF-beta receptor.

Experimental Example  2: promoting cell proliferation

Human normal fibroblasts were inoculated (5x10 ³ cells / well) into 96-well microplates containing DMEM medium containing 10% fetal bovine serum and incubated with 5% CO ₂ (CO ₂ ) ₂ incubator at 37 < 0 > C for 24 hours. Normal human fibroblasts were purchased from Cascade (USA). A DMEM medium containing no serum containing various concentrations of beta-raffone was prepared, and the medium was replaced with this medium for 24 hours and 48 hours. Then, 0.2% MTT solution (3- [4,5-dimethylthiazol-2 -yl] -2,5-diphenyltetrazolium bromide) was added in an amount of 50 μl per well, and the mixture was incubated at 37 ° C. for 4 hours. The formazane thus formed was dissolved in DMSO (dimethyl sulfoxide). Absorbance of dissolved formazan was measured at 570 nm using a microplate reader. The cell proliferation rate was calculated according to the following equation (1), and the result is shown in Fig.

[Equation 1]

Cell proliferation rate (%) = [(A x 100) / B] -100

(In the above equation (1), A is the absorbance of the sample addition well and B is the absorbance of the well to which the sample is not added)

FIG. 2 is a graph showing the cell proliferative activity according to the concentration of beta-raffonone. It was able to promote cell proliferation in a concentration-dependent manner by the addition of beta-raffonone. In particular, about 50% It can be seen that the promoting effect appears.

Experimental Example 3: Promotion of cell migration

Human normal keratinocytes were inoculated (1 x 10 ⁶ cells / well) into a 6-well plate containing Epilife medium (Gibco, USA) containing 10% fetal bovine serum and incubated at 5% CO ₂ ) in a CO ₂ incubator at 37 ° C for 24 hours. Each well was washed twice with the serum-free culture medium, and then scratch damage was induced by making a wound on the cells using a micro tip. The DMEM medium containing no serum containing various concentrations of beta-raffone was prepared, and after replacing with this medium for 24 hours, the extent to which the scratched wound was recovered was confirmed, and the results are shown in FIG.

FIG. 3 is a photograph showing the cell migration according to the concentration of the negative control and the beta-rapacon. The wound of the cells treated with the negative control remained relatively unhealed after 24 hours, whereas the beta-rapacon was 0.05 ug / mL, and 0.1 ug / mL, respectively, cell migration and cell migration were 17% and 27%, respectively.

Experimental Example  4: Beta- Rafacon  Confirming the promotion of skin regeneration of formulations containing

In order to confirm the skin regeneration effect of the beta-rapacon according to the present invention, a cream formulation containing 0.0001% of beta-raffone was prepared and the human clinical trial was conducted.

30 creams from 30 to 60 years old were applied to the eyes of both sides of the face twice a day for 8 weeks, respectively. Derma Top-blue (Breuckmann Corporation, Germany) was used to measure changes in skin roughness before and after use with various parameters, and the obtained results are shown in Table 1 below.

The change in skin elasticity before and after use of the product was measured using MPA5 (Courage-Khazaka electronic GmbH, Germany). The obtained results are shown in Tables 1 and 4 below. Here, FIG. 4 is a photograph showing the skin condition before and after using the beta-raffon cream and the placebo cream, respectively.

≪ 3D roughness parameters >

- Spt: Maximum height and minimum valley distance during skin flexion

- Spa: Average distance between high and low bends

- Sdev: Area when the bending part is flatly opened when the analysis area is 1

- Sptm: Average distance between peaks and valleys (sum of 5 peaks maximum and 5 lowest peaks)

parameter Before use After 8 weeks use Example (Beta-Raffoon Cone-containing Cream) Spt 0.631 + 0.285 0.512 + 0.124 Spa 0.038 ± 0.006 0.033 0.006 Sdev 1.043 + 0.029 0.966 + 0.020 Sptm 0.284 + 0.023 0.271 + 0.018 Comparative Example (Placebo Cream) Spt 0.626 + 0.337 0.593 + 0.136 Spa 0.037 ± 0.008 0.036 ± 0.005 Sdev 1.042 + 0.024 1.038 + 0.023 Sptm 0.289 + 0.033 0.287 ± 0.021

Referring to Table 1 and FIG. 4, when the cream containing beta-rapacon according to the present invention was applied to the skin, the skin roughness was improved and the exfoliation efficiency was improved after 8 weeks of use compared with the placebo cream Able to know.

Hereinafter, a preferred formulation example is provided to facilitate understanding of the present invention. However, the following formulation examples are provided only for a better understanding of the present invention, and the present invention is not limited by the formulation examples.

Formulation Example  1: Softened longevity (skin lotion)

The softening water containing beta-rapacon was prepared according to a conventional method as shown in Table 2 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 glycerin 5.0 1,3-butylene glycol 3.0 PEG 1500 1.0 Allantoin 0.1 DL-Panthenol 0.3 EDTA-2Na 0.02 Benzophenone-9 0.04 Sodium hyaruronate 5.0 ethanol 10.0 Octyldodec-16 0.2 Polysorbate 20 0.2 incense 0.02 Unicide - Yu 13 0.01 Green # 13 0.001 Distilled water Balance Sum 100

Formulation Example  2: convergent lotion

Convergent lotion containing beta-rapacon was prepared according to the usual method as shown in Table 3 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 glycerin 2.0 1,3-butylene glycol 2.0 Allantoin 0.2 DL-Panthenol 0.2 EDTA-2Na 0.02 Benzophenone-9 0.04 Sodium hyaruronate 3.0 ethanol 15.0 Polysorbate 20 0.3 Location Hagel extract 2.0 Citric acid a very small amount incense 0.02 Unicide - Yu 13 0.01 Green # 13 0.001 Distilled water Balance Sum 100

Formulation Example  3: Nourishing lotion

A nutritional lotion containing beta-rapacon was prepared according to a conventional method as shown in Table 4 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 Glyceryl stearate SE 1.5 Cetearyl alcohol 1.5 lanolin 1.5 Polysorbate 60 1.3 Sorbitan stearate 0.5 Hardened vegetable oil 1.0 Mineral oil 5.0 Squalane 3.0 Trioctanoin 2.0 Dimethicone 0.8 Tocopheryl acetate 0.5 Carboxyvinyl polymer 0.12 glycerin 5.0 1,3-butylene glycol 3.0 Sodium hyaruronate 5.0 Triethanolamine 0.12 incense 0.01 Unicide - Yu 13 0.02 Green # 3 0.003 Distilled water Balance Sum 100

Formulation Example  4: Nourishing cream

Nutritive creams containing beta-rapacon were prepared according to conventional methods as shown in Table 5 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 Pro-type glycerin monostearate 2.0 Cetearyl alcohol 2.2 Stearic acid 1.5 Wax 1.0 Polysorbate 60 1.5 Sorbitan stearate 0.6 Hardened vegetable oil 1.0 Squalane 3.0 Mineral oil 5.0 Trioctanoin 5.0 Dimethicone 1.0 Sodium magnesium silicate 0.1 glycerin 5.0 Betaine 3.0 Triethanolamine 1.0 Sodium hyaruronate 4.0 incense 0.01 Unicide - Yu 13 0.02 Green # 3 0.003 Distilled water Balance Sum 100

Formulation Example  5: Massage  cream

Massage cream containing beta-rapacon was prepared according to the usual method as shown in Table 6 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 Pro-type glycerin monostearate 1.5 Cetearyl alcohol 1.5 Stearic acid 1.0 Polysorbate 60 1.5 Sorbitan stearate 0.6 Isostearyl isostearate 5.0 Squalane 5.0 Mineral oil 35 Dimethicone 0.5 Hydroxyethylcellulose 0.12 glycerin 6.0 Triethanolamine 0.7 incense 0.01 Unicide - Yu 13 0.02 Green # 3 0.003 Distilled water Balance Sum 100

Formulation Example  6: Essence

Essences containing beta-rapacon were prepared according to the conventional method as shown in Table 7 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 glycerin 10 Betaine 5.0 PEG 1500 2.0 Allantoin 0.1 DL-Panthenol 0.3 EDTA-2Na 0.02 Benzophenone-9 0.04 Hydroxyethylcellulose 0.1 Sodium hyaruronate 8.0 Carboxyvinyl polymer 0.2 Triethanolamine 0.18 Octyldodecanol 0.3 Octyldodec-16 0.4 ethanol 6.0 incense 0.02 Unicide - Yu 13 0.01 Green # 3 0.001 Distilled water Balance Sum 100

Formulation Example  7: Pack

A pack containing beta-rapacon was prepared according to the conventional method as shown in Table 8 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 Polyvinyl alcohol 15.0 Cellulose sword 0.15 glycerin 3.0 PEG 1500 2.0 Cyclodextrin 0.15 DL-Panthenol 0.4 Allantoin 0.1 Monoammonium glycyrrhizin acid 0.3 Nicotinamide 0.5 ethanol 6.0 PEG 40 hardened castor oil 0.3 incense 0.01 Unicide - Yu 13 0.02 Green # 3 0.003 Distilled water Balance Sum 100

Formulation Example  8: Ointment

Ointment containing beta-rapacon was prepared according to the conventional method as shown in Table 9 below.

ingredient Content (% by weight) Beta-Lapcon 0.0001 Purified water Remainder Cetostearyl alcohol 3.0 Hard liquid paraffin 5.0 Tocopherol acetate 2.0 Ceteareth-20 3.0 Panthenol 0.5 Methyl paraoxybenzoate Suitable amount P-hydroxybenzoic acid profile Suitable amount

Claims (7)

A pharmaceutical composition for promoting wound healing and skin regeneration comprising beta-rapacon represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]

The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises beta-rapacon, or a pharmaceutically acceptable salt thereof, in an amount of 0.00001 to 10.0% by weight based on the total weight of the composition. A pharmaceutical composition. The pharmaceutical composition for promoting wound healing and skin regeneration according to claim 1, wherein the pharmaceutical composition is in a liquid, cream, paste, or solid form. A cosmetic composition for promoting wound healing and skin regeneration comprising beta-raffonone represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]

[Claim 5] The cosmetic composition according to claim 4, wherein the beta-raffon cone has an effect of improving wounds and promoting skin regeneration. [Claim 5] The cosmetic composition according to claim 4, wherein the cosmetic composition comprises beta-raffone or a pharmaceutically acceptable salt thereof in an amount of 0.00001-10.0 wt% based on the total weight of the composition. Cosmetic composition. The cosmetic composition according to claim 4, wherein the cosmetic composition is at least one selected from the group consisting of softening agents, convergent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, gel, powder, , Body cream, body oil, and body essence. ≪ Desc / Clms Page number 25 >

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