KR20230097841A - Composition for preventing hair loss and promoting hair growth - Google Patents

Abstract

The present invention relates to a composition for preventing hair loss or promoting hair growth comprising EGF (Epidermal Growth Factor) and PDGF-C as active ingredients. , It relates to a pharmaceutical composition and a cosmetic composition for promoting hair growth or hair growth. The composition of the present invention not only has no side effects even upon long-term administration in hair loss, which is a chronic disease, but also shows excellent and stable efficacy in hair growth and hair growth, and exhibits a synergistic effect, especially when used in combination with minoxidil, to prevent or treat hair loss, or hair growth or It can be usefully used as a quasi-drug for promoting hair growth and a cosmetic composition.

Description

Composition for preventing hair loss and promoting hair growth containing EGF (Epidermal Growth Factor) as an active ingredient

The present invention relates to a composition for preventing hair loss or promoting hair growth comprising EGF (Epidermal Growth Factor) and PDGF-C as active ingredients, and more particularly, to a composition for preventing hair loss, treating hair loss, and promoting hair growth containing PDGF-C as an active ingredient. It relates to a pharmaceutical composition and a cosmetic composition for promoting or promoting hair growth.

Recently, as interest in beauty has increased, interest in hair loss treatment has also increased. Currently, the most commonly used methods for hair loss treatment are self-transplantation surgery using one's own hair and drug treatment using Minoxidil and Propecia.

Minoxidil induces hair growth through increased nutrient supply to hair cells through vasodilation and potassium channel opening effect, while Propecia induces hair growth by inhibiting the production of DHT (dihydrotestosterone). is to do Both of these drugs show hair growth effect at the time of treatment, but when treatment is stopped, hair loss proceeds again, and the effect of preventing hair loss is greater than the effect of hair growth. In particular, side effects such as sexual dysfunction and birth defects in pregnant women occur. There are problems that may appear.

Various growth factors and cytokines are involved in the regulation of the hair follicle cycle. For example, EGF (epidermal growth factor), TGF-a (transforming growth factor-a), TGF-b (transforming growth factor-b),

KGF (keratinocy tegrowth factor), IGF (insulin like growth factor), interleukin-1, bHGF (basic fibrovlast growth factor), VEGF (vascular endothelial growth factor), etc. are included (Wagana P. et al. , In vivo distribution of arsonoliposomes: Effect of vesicle lipid composition, Journal of Pharmaceutics, 2008:347:86-92).

PDGF (platelet-derived growth factor) is one of the growth factors that regulate cell growth and division (Andrae et al., Genes Dev 22:1276-1312, 2008; Kim et al., Development 130: 4769-4784, 2003), and affects the proliferation and migration of undifferentiated mesenchymal stem cells and some progenitor cells as a mitogen in early development (Hannink et al., Biochim Biophys Acta 989:1-10, 1989; Heldin et al., EMBO J 11:4251-4259, 1992). In late morphogenesis, PDGF signaling is involved in tissue remodeling and cell differentiation, and in particular plays an important role in angiogenesis.

The PDGF signaling network consists of four ligands, PDGF-A, -B, -C, and D, and two tyrosine kinase receptors, PDGFR-α and PDGFR-β (Demoulin JB et al., Cytokine Growth Factor Rev 25 :273-283, 2014; Levitzki A et al., Cytokine Growth Factor Rev 15:229-235, 2004). PDGF-C and -D bind to PDGFR-a and PDGFR-β, respectively (Bergsten E et al. Nat Cell Biol 3:512-516, 2001; LaRochelle WJ et al., Nat Cell Biol 3:517-521, 2001).

The mitosis-promoting effect of PDGF-B is known in adipose stem cells, and it has been confirmed that PDGF-A and PDGF-B have hair growth induction and hair growth effects when mice are treated (Y. Tomita et al. Journal of Dermatological Science (2006) 43, 105-115). However, the hair growth effect or hair loss prevention effect of PDGF-C and PDGF-D has not yet been confirmed.

Accordingly, the present inventors have tried to find a method capable of preventing hair loss or promoting hair growth or hair growth without side effects. As a result, it was confirmed that PDGF-C effectively promotes hair growth and hair growth and prevents hair loss, and in particular, it was confirmed that the effect of preventing hair loss and promoting hair growth significantly increased when administered in combination with minoxidil, thereby completing the present invention.

Accordingly, an object of the present invention is for preventing or treating hair loss, or for hair growth or hair growth, containing EGF (Epidermal Growth Factor) and PDGF-C (platelet-derived growth factor-C) or a pharmaceutically acceptable salt thereof as active ingredients. It is to provide a pharmaceutical composition for promotion.

Another object of the present invention is to provide a cosmetic composition for preventing or improving hair loss, or for promoting hair growth or hair growth, comprising EGF (Epidermal Growth Factor) and PDGF-C or a cosmetically acceptable salt thereof as active ingredients.

The present invention is to solve the above problems, and is for preventing or treating hair loss, or for promoting hair growth or hair growth, comprising PDGF-C (platelet-derived growth factor-C) or a pharmaceutically acceptable salt thereof as an active ingredient. A pharmaceutical composition is provided.

According to a preferred embodiment of the present invention, the pharmaceutical composition may further include minoxidil.

According to another preferred embodiment of the present invention, the pharmaceutical composition is an external preparation for skin, which is selected from the group consisting of creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents. It may be the formulation of choice.

In addition, the present invention provides a cosmetic composition for preventing or improving hair loss, or for promoting hair growth or hair growth, comprising PDGF-C or a cosmetically acceptable salt thereof as an active ingredient.

According to a preferred embodiment of the present invention, the cosmetic composition may further include minoxidil.

According to another preferred embodiment of the present invention, the cosmetic composition is a scalp tonic, scalp lotion, scalp cream, scalp serum, scalp essence, scalp ampoule, scalp treatment, scalp conditioner, scalp shampoo, scalp pack, hair tonic, Hair lotion, hair cream, hair spray, hair mousse, hair gel, hair conditioner, hair shampoo, hair conditioner, hair book, hair treatment, eyebrow hair growth agent, eyelash growth agent, eyelash nourishment, pet shampoo or conditioner for pets It may be a form.

The present invention has been made to solve the above problems, for preventing or improving hair loss containing EGF (Epidermal Growth Factor) and PDGF-C (platelet-derived growth factor-C) or a salt thereof as active ingredients, or It is intended to provide a composition for promoting hair growth or hair growth.

The composition of the present invention not only has no side effects even when administered for a long period of time in hair loss, a chronic disease, but also shows excellent and stable efficacy in hair growth and hair growth, and exhibits a synergistic effect, especially when used in combination with minoxidil, to prevent or treat hair loss, or hair growth or It can be usefully used as a quasi-drug for promoting hair growth and a cosmetic composition.

1 is a result confirming the effect of increasing hair length by PDGF-C treatment in beard tissue culture (Vibrissae hair organ culture) according to an embodiment of the present invention.
Figure 2 is a result confirming the dermal papilla cell proliferation effect by PDGF-C treatment according to an embodiment of the present invention.
Figure 3 is a result confirming the synergistic effect by the combined administration of PDGF-C and minoxidil according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail.

Since the PDGF-C of the present invention can exhibit a significant hair growth promoting effect by inducing hair anagen in hairless mice, etc., there is an effect of providing a composition effective for preventing hair loss and promoting hair growth.

Accordingly, the present invention provides a pharmaceutical composition for preventing or treating hair loss, or for promoting hair growth or hair growth, comprising PDGF-C or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, "PDGF-C" or "platelet-derived growth factor-C" is one of the growth factors that induce cell proliferation and differentiation, and is derived from mesenchymal cells such as smooth muscle cells, fibroblasts, and blood vessel walls. A protein that promotes cell proliferation.

The term "hair loss" of the present invention refers to a phenomenon in which hair completely comes out of the scalp. A person undergoing hair loss has a hair cycle with a short anagen phase and a long telogen phase. As demonstrated in the following examples, PDGF-C converts hair from the anagen phase to the anagen phase and promotes hair growth and hair-related growth in skin tissues. By increasing the expression of the factor, it was confirmed that there is an effect of preventing, improving or treating hair loss.

The term "hair growth" of the present invention means that hair grows on the scalp, and "hair growth" means that the length of hair is lengthened (ie, hair growth), and is the same as "wool", another term used in the art. used in meaning

The PDGF-C is preferably an external composition for skin, and the pharmaceutical composition for external skin containing PDGF-C as an active ingredient of the present invention is an external skin preparation for preventing hair loss, improving and promoting hair growth, including creams, gels, patches, sprays, It can be prepared and used as a pharmaceutical composition in the form of an ointment, warning agent, lotion, liniment agent, pasta agent or cataplasma agent for external application to the skin, but is not limited thereto.

PDGF-C of the present invention can be used in the form of a pharmaceutically acceptable salt, and an acid addition salt formed from a pharmaceutically acceptable free acid is useful as the salt. Acid addition salts are formed with 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, hydroxy alkanoates and alkanes. Obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. These pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulphate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, iodine. Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate , sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Toxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycol Lates, maleates, tartrates, methanesulfonates, propanesulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates or mandelates.

The acid addition salt according to the present invention is prepared by a conventional method, for example, dissolving the PDGF-C in an excess acid aqueous solution, and using the salt in a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. It can be prepared by precipitating it. It can also be prepared by heating equal amounts of PDGF-C and an acid or alcohol in water, then evaporating the mixture to dryness, or suction filtering the precipitated salt.

In addition, a pharmaceutically acceptable metal salt may be prepared using a base. An alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare a sodium, potassium or calcium salt as the metal salt. Also, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

In addition, the PDGF-C of the present invention includes not only pharmaceutically acceptable salts, but also all salts, hydrates and solvates that can be prepared by conventional methods.

The addition salt according to the present invention can be prepared by a conventional method. For example, PDGF-C is dissolved in a water-miscible organic solvent such as acetone, methanol, ethanol, or acetonitrile, and an excessive amount of an organic acid is added or an inorganic acid is added. It can be prepared by precipitating or crystallizing after adding an aqueous acid solution. Then, after evaporating the solvent or excess acid from this mixture, it may be dried to obtain an addition salt, or the precipitated salt may be suction filtered.

When the composition of the present invention is used as a pharmaceutical, the pharmaceutical composition containing PDGF-C or a pharmaceutically acceptable salt thereof as an active ingredient is formulated and administered in various oral or parenteral dosage forms at the time of clinical administration. It may, but is not limited thereto.

Formulations for oral administration include, for example, tablets, pills, hard/soft capsules, solutions, suspensions, emulsifiers, syrups, granules, and elixirs. rose, sucrose, mannitol, sorbitol, cellulose and/or glycine), lubricants (eg silica, talc, stearic acid and its magnesium or calcium salts and/or polyethylene glycol). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt. may contain disintegrants or effervescent mixtures and/or absorbents, colorants, flavors, and sweeteners.

The pharmaceutical composition comprising PDGF-C or a pharmaceutically acceptable salt thereof of the present invention as an active ingredient can be administered parenterally, and parenteral administration is a method of injecting subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection. depends on At this time, in order to formulate a formulation for parenteral administration, the PDGF-C or a pharmaceutically acceptable salt thereof is mixed in water together with a stabilizer or buffer to prepare a solution or suspension, which is prepared in an ampoule or vial unit dosage form. can The composition may be sterilized and/or contain preservatives, stabilizers, hydration agents or emulsification accelerators, adjuvants such as salts and/or buffers for osmotic pressure control, and other therapeutically useful substances, which are conventional methods such as mixing and granulation. It can be formulated according to the coating or coating method.

In addition, the dose of the compound of the present invention to the human body may vary depending on the patient's age, weight, sex, dosage form, health condition and disease degree, and when based on an adult patient weighing 60 kg, it is generally 0.001 to 1,000 mg/day, preferably 0.01 to 500 mg/day, and may be administered in divided doses once a day to several times at regular time intervals according to the judgment of a doctor or pharmacist.

In addition, the present invention provides a quasi-drug for preventing or improving hair loss, or for promoting hair growth or hair growth, comprising PDGF-C or a pharmaceutically acceptable salt thereof as an active ingredient. Details of the PDGF-C are as described above.

When the PDGF-C of the present invention is used as an active ingredient in a quasi-drug composition, the PDGF-C, which exhibits the effect of preventing hair loss and promoting hair growth, may be added as it is or used together with other quasi-drugs or quasi-drug components, and according to a conventional method can be used appropriately. The mixing amount of the active ingredient can be suitably determined depending on the purpose of use.

The quasi-drug composition for preventing hair loss and promoting hair growth of the present invention is not particularly limited in its dosage form, and may be formulated in various forms as quasi-drugs known in the art to prevent hair loss and promote hair growth. The formulated quasi-drugs are scalp tonic, scalp lotion, scalp cream, scalp serum, scalp essence, scalp ampoule, scalp treatment, scalp conditioner, scalp shampoo, scalp pack, hair tonic, hair lotion, hair cream, hair spray, hair Mousse, hair gel, hair conditioner, hair shampoo, hair conditioner, hair pack, hair treatment, eyebrow hair growth agent, eyelash growth agent, eyelash nourishment, pet shampoo, pet conditioner, hand sanitizer, detergent soap, soap, disinfectant, There are wet tissues, masks, ointments, patches or filter fillers, etc., and includes all quasi-drugs in a conventional sense.

In addition, in each formulation, the quasi-drug composition for preventing hair loss and promoting hair growth may be combined with other ingredients selected arbitrarily according to the formulation or purpose of use of other quasi-drugs. The mixing amount of the active ingredient may be suitably determined depending on the purpose of use, and may include, for example, thickeners, stabilizers, solubilizers, vitamins, pigments, and conventional auxiliary agents such as flavoring agents, carriers, and the like.

The content of the composition is preferably 0.0001 to 10% by weight, respectively, based on the total weight, and if it exceeds 10% by weight, the color and stability of the composition are poor, and if it is less than 0.0001% by weight, the effect is insignificant. there is The quasi-drug composition containing PDGF-C as an active ingredient of the present invention can be usefully used as a quasi-drug material because it has little toxicity and side effects to cells, as confirmed in the therapeutic index.

In addition, the present invention provides a cosmetic composition for preventing or improving hair loss, or for promoting hair growth or hair growth, comprising PDGF-C or a pharmaceutically acceptable salt thereof as an active ingredient.

Ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions in addition to PDGF-C or a pharmaceutically acceptable salt thereof as an active ingredient, such as antioxidants, stabilizers, solubilizers, vitamins, and pigments. and conventional adjuvants such as perfumes, and carriers.

The cosmetic composition of the present invention can be prepared in any formulation commonly prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , Oil, powder foundation, emulsion foundation, wax foundation and spray may be formulated, but is not limited thereto.

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

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane / May contain a propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyl glycol oil, fatty acid esters of glycerol, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Star cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like may be used.

When the formulation of the present invention is a surfactant-containing cleanser, as carrier components, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The pharmaceutical composition or cosmetic composition containing PDGF-C or an acceptable salt thereof of the present invention as an active ingredient can significantly increase the effect of preventing or improving hair loss or promoting hair growth or hair growth by using it in combination with minoxidil. It was confirmed in the following examples that the synergistic effect of the combined administration was remarkable compared to the case of using PDGF-C or minoxidil alone.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for exemplifying the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.

Example 1. Hair growth effect according to PDGF-C treatment in beard tissue culture

In order to confirm the hair growth effect of PDGF-C, beard tissue culture (Vibrissae hair organ culture) experiments were performed. Specifically, vibrissae hair follicles from 4-week-old c57bl/6 mice were isolated and cultured in a 6-well plate. Controls were 2 mM L-glutamine, 10 μg/ml insulin, 10 ng/ml hydrocortisone, 100 U/ml penicillin and 100 μg/ml streptomycin. was used, and in the experimental group, 20 ng/ml PDGF-C was added to the same medium and cultured. After 3 days, hair follicles were observed under a microscope and the length of vibrissae was measured.

As a result, as shown in FIG. 1, it was confirmed that the length of the beard cultured in the medium containing the PDGF-C protein was significantly increased compared to the control group.

Example 2. Dermal papilla cell proliferation effect according to PDGF-C treatment

In order to confirm the hair growth effect of PDGF-C, the proliferation of dermal papilla cells was confirmed. Specifically, dermal papilla cells (purchased from PromoCell) were divided into 3 groups and treated with the protein PDGF-C (purchased from PepproTech) at different concentrations (0, 1, 5 ng/ml) for 1 to 3 days. Every day, all cells were treated with trypsin, removed from the plate, stained with trypan blue, and the number of dermal papilla cells was directly counted.

As a result, as shown in Figure 2, it was found that the growth of PDGF-C-treated dermal papilla cells significantly increased compared to the control group.

Example 3. Synergistic effect of combined administration of PDGF-C and minoxidil

To confirm the effect of using PDGF-C and minoxidil together, the backs of 6.5-week-old C3H mice were shaved and divided into four groups. For each of the three experimental groups, 1 μg of 2% minoxidil (Rogain), 1 μg of PDGF-C, or 1 μg of minoxidil/PDGF-C were evenly applied to the back, and no treatment was applied to the control group. After treatment with each drug for 14 days, photos were taken to compare hair growth results, and hair on the back of each experimental group was removed and then the hair weight was measured.

As a result, as shown in FIG. 3, when PDGF-C was administered alone, the hair growth effect was not noticeable with the naked eye, and the minoxidil alone administration group slightly increased compared to the control group, but it was not significant. On the other hand, it was confirmed that the combined administration of minoxidil and PDGF-C significantly increased hair compared to the control group and the minoxidil alone administration group.

skip

Claims (4)

A pharmaceutical composition for preventing or treating hair loss, or for promoting hair growth or hair growth, comprising epidermal growth factor (EGF) and platelet-derived growth factor-C (PDGF-C) or a pharmaceutically acceptable salt thereof as active ingredients.
According to claim 1,
A pharmaceutical composition, characterized in that it further comprises minoxidil (Minoxidil) in the composition. According to claim 1,
The pharmaceutical composition for preventing or treating hair loss, characterized in that the pharmaceutical composition is a formulation selected from the group consisting of creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents and cataplasma agents as external preparations for skin , Or a pharmaceutical composition for promoting hair growth or hair growth.
A cosmetic composition for preventing or improving hair loss, or for promoting hair growth or hair growth, comprising epidermal growth factor (EGF) and platelet-derived growth factor-C (PDGF-C) or a cosmetically acceptable salt thereof as active ingredients.

Images