KR102021836B1 - Composition for prevention, treatment or improvement of hair loss - Google Patents

Abstract

The present invention provides a composition for preventing, treating or ameliorating alopecia containing a polypeptide comprising some amino acid sequences of proteins CXXC4 and CXXC5 present in the body. The polypeptide comprising the amino acid sequence can alleviate the progress of hair loss, promote hair / hair growth, and growth of hair, and is effective for preventing, treating or improving alopecia.

Description

Composition for prevention, treatment or improvement of hair loss

The present invention relates to a composition for preventing, treating or improving alopecia.

The human hair is about 100,000 to 150,000 pieces, and each hair has a different cycle and repeats the anagen, the catagen, and the telogen. In the growth phase, the hair grows to produce keratin, and the degeneration phase grows slowly as the metabolic process slows down while maintaining the shape of the hair. In the degenerative period, keratin is not produced and cell division of hair follicles stops and is rapidly contracted. In the next off-season period, the hair follicles cease to be fully active and ready for hair loss, which is pushed out by the newly growing hair at the base of the resting hair and falls out on its own and repeats the cycles of physical action such as combing or washing the hair. This cycle is repeated over three to six years, resulting in the normal loss of 100 hairs per day.

As described above, since human hair has a hair cycle, it maintains a constant number of hairs without molting. However, as bald progresses, the nipples present in the hair roots become smaller, and as the nipples become smaller, the thickness of the hair becomes thinner and the hair growth becomes shorter, and the newly grown hair becomes thinner. Therefore, as bald progresses, the hair turns into fluffy hairs, and the hair cycle becomes shorter, and then grows a little and falls out.

As bald progresses, oil increases in the scalp, causing seborrheic dermatitis, and the sebaceous glands attached to the hair roots gradually become larger and produce more sebum, which is not the cause of baldness, but it is secondary to baldness or this phenomenon promotes hair loss again. It causes.

The cause of hair loss is a genetic cause largely, and not only men's problems but also women's hair loss is increasing as a serious problem recently. In addition to hereditary factors, imbalanced hormones, mental stress in social life, exposure to air pollution, processed foods, severe illness due to high fever, nutritional imbalances, taking anticancer and antithyroid drugs, oral contraceptives, shampoos, strong UV rays In addition, various habits and circumstances such as sweating during exercise, eating habits, and psychological pressure are known as the culprit.

Minoxidil and finasteride are representative drugs used to promote hair growth. Minoxidil from the US Upzone may cause side effects such as swelling, arrhythmia and unwanted hairs on long term application.The effect of minoxidil is most effective between 6 months and 1 year from use and then gradually It is known that the effect is reduced. Finasteride, developed by Merck, is known to inhibit the activity of 5-α-reductase, an enzyme that acts on male hormone testosterone metabolism in hair follicles. An increase in suicidal thoughts has been reported. In addition, it is not applicable to women of childbearing age or pregnant women because it increases the probability of birth of birth defects. Moreover, it is known that hair loss progresses again if both drugs are discontinued. There is also Valproic acid, but taking it during pregnancy is known to greatly reduce the child's cognitive development ability. As mentioned above, various types of conventional hair regrowth have been attempted to help hair growth for the purpose of promoting blood circulation of the scalp and nourishing hair roots. However, the present invention is also toxic and side effects are severe and the effect is insufficient. .

Accordingly, the present inventors have made efforts to develop a substance capable of preventing hair loss and promoting hair growth without side effects. As a result, peptides composed of some amino acid sequences of proteins CXXC4 and CXXC5 present in the body have an effect of promoting hair growth. It confirmed and completed this invention.

The association of hair loss with polypeptides consisting of some amino acid sequences of CXXC4 and CXXC5 is not known yet.

Matsushita and Matsui, (2005), Protein transduction technology. J Mol Med 83, 324-328

It is an object of the present invention to provide a composition for preventing, treating or improving alopecia.

In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of alopecia containing a polypeptide having a amino acid sequence of SEQ ID NO: 1 to 13 to 55 amino acids.

In one embodiment, the polypeptide may be a pharmaceutical composition for preventing or treating alopecia, wherein an amino acid sequence encoding a protein transduction domain (PTD) is additionally inserted into the amino acid sequence of SEQ ID NO: 1.

In other embodiments, the PTD can be Poly R ₈ , HIV-Tat, HSV VP22, Antp or Transportan.

In another embodiment, the polypeptide may be a linker further inserted between the amino acid sequence of SEQ ID NO: 1 and the amino acid sequence encoding the PTD.

In another embodiment, the alopecia is alopecia areata, hereditary androgen alopecia, resting alopecia, traumatic alopecia, hair growth wall, pressure alopecia, growth alopecia, nasal alopecia, syphilis alopecia, seborrheic alopecia, symptomatic alopecia, scarring alopecia, Or may be selected from the group consisting of congenital alopecia.

In another embodiment, the pharmaceutical composition may be in the form of a cream, lotion, shampoo, gel, or pack.

The present invention provides a cosmetic composition for improving alopecia containing a polypeptide having a amino acid sequence of SEQ ID NO: 1 to 13 to 55 amino acids.

In one embodiment, the polypeptide may be a cosmetic composition for improving alopecia in which an amino acid sequence encoding PTD (protein transduction domain) is additionally inserted into the amino acid sequence of SEQ ID NO: 1.

In other embodiments, the PTD can be Poly R ₈ , HIV-Tat, HSV VP22, Antp or Transportan.

In another embodiment, the polypeptide may further include a linker inserted between the amino acid sequence of SEQ ID NO: 1 and the amino acid sequence encoding the PTD.

In another embodiment, the alopecia is alopecia areata, hereditary androgen alopecia, resting alopecia, traumatic alopecia, hair growth wall, pressure alopecia, growth alopecia, nasal alopecia, syphilis alopecia, seborrheic alopecia, symptomatic alopecia, scarring alopecia, Or may be selected from the group consisting of congenital alopecia.

In another embodiment, the cosmetic composition is an external preparation for skin, hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder gel, hair pack, hair treatment, eyebrow regrowth , Eyelash regrowth, eyelash nutritional preparations.

The composition comprising the polypeptide having the amino acid sequence of SEQ ID NO: 1 according to the present invention, as well as pharmaceutically available as a hair loss prevention and hair growth promoting composition, can also be usefully used as a cosmetic composition.

1 shows that hair growth was promoted in the skin of mice treated with PolyR ₈ -HFAP.
Figure 2 is a tissue staining result showing that the growth of the hair growth stage in the experimental group treated with PolyR ₈ -HFAP while the control group is mostly rest hair.
Figure 3 is an analysis showing that the number of hair follicles in the growing phase significantly increased in the experimental group treated with PolyR ₈ -HFAP.
4 is a tissue fluorescence staining result showing that the epidermal differentiation markers, lyricin, filaggrin, keratin 14, which showed the hair growth stage in the experimental group treated with PolyR ₈ -HFAP, were significantly increased.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for preventing, treating or improving alopecia containing a polypeptide having 13 to 100 amino acid sequences comprising the amino acid sequence of SEQ ID NO: 1.

The present invention also provides a composition for the prevention, treatment or amelioration of alopecia containing a polypeptide having 13 to 75 amino acid sequences comprising the amino acid sequence of SEQ ID NO: 1.

The present invention also provides a composition for the prevention, treatment or amelioration of alopecia containing a polypeptide having 13 to 55 amino acid sequences comprising the amino acid sequence of SEQ ID NO: 1.

The present invention also provides a composition for preventing, treating or improving alopecia containing a polypeptide having 13 to 30 amino acid sequences comprising the amino acid sequence of SEQ ID NO: 1.

SEQ ID NO: RKTGHQICKFRKC

The amino acid sequence of SEQ ID NO: 1 corresponds to some amino acid sequences of proteins CXXC4 and CXXC5 present in the body. As shown in the following examples and figures, the inventors have applied eight arginine to the amino terminus side of a polypeptide having the amino acid sequence of SEQ ID NO: 1 and applied it to the skin of a mouse to increase epidermal differentiation markers related to hair growth. And it was confirmed that the hair in the growth phase has increased. Therefore, the polypeptide comprising the amino acid sequence of SEQ ID NO: 1 of the present invention can be used to prevent, treat or improve alopecia. The present invention therefore provides a use for the prevention, treatment or amelioration of alopecia of a composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 1. The present invention also provides a method for preventing, treating or ameliorating alopecia of a composition containing a polypeptide comprising the amino acid sequence of SEQ ID NO: 1.

The present invention also provides a composition for preventing, treating or improving alopecia comprising a polypeptide in which an amino acid sequence encoding PTD (protein transduction domain) is additionally inserted into the amino acid sequence of SEQ ID NO: 1.

PTD mainly consists of basic amino acids, such as arginine and lysine, and it can induce penetration into a cell by adding PTD to N-terminal or C-terminal of the amino acid sequence of SEQ ID NO: 1. Specific examples of PTD are known in the art, and the type of PTD introduced into the amino acid of SEQ ID NO: 1 is not particularly limited.

In one embodiment, the PTD can be poly R ₈ , HIV-Tat, HSV VP22, Antp or Transportan. For example, poly R ₈ is the amino acid sequence of SEQ ID NO: 2, HIV-Tat may have an amino acid sequence of SEQ ID NO: 3, HSV VP22 may have an amino acid sequence of SEQ ID NO: 4, Antp may have an amino acid sequence of SEQ ID NO: 5, or Transportan may have an amino acid sequence of SEQ ID NO: 6.

SEQ ID NO: RRRRRRRR

SEQ ID NO: 3 YGRKKRRQRRR

SEQ ID NO: DAATATRGRSAASRPTERPRAPARSASRPRRPVE

SEQ ID NO: 5: RQIKIWFQNRRMKWKK

SEQ ID NO: AGYLLGKINLKALAALAKKIL

In another embodiment, the polypeptide may further include a linker inserted between the amino acid sequence of SEQ ID NO: 1 and the amino acid sequence encoding the PTD. Specific examples of linkers are known in the art, and the type of linker inserted between the amino acid sequence of SEQ ID NO: 1 and the amino acid sequence encoding the PTD is not particularly limited. In one embodiment, the linker may consist of 4 to 12 amino acid sequences, such as 4 to 8 glycine. For example, a polypeptide with an additional linker inserted may have an amino acid sequence of SEQ ID NO.

SEQ ID NO: 7: RRRRRRRRGGGGRKTGHQICKFRKC

In the present invention, alopecia is alopecia areata, hereditary androgen alopecia, telogen effluvium, traumatic alopecia, tricotillomania, pressure alopecia, growth alopecia, non It may be selected from the group consisting of alopecia areata, Alopecia syphlltiac, Alopecia seborrhecia, symptomatic alopecia, scarring alopecia, or congenital alopecia.

The compositions of the present invention have formulations that can be administered by methods such as direct application or spreading on the skin, such as hair or scalp, such as creams, lotions, ointments, aerosols, shampoos, gels, or packs. It may be. Methods for the formulation or formulation suitable for each formulation are well known in the art. Those skilled in the art can appropriately select and use various combinations of ingredients used to prepare conventional external preparations in preparing these formulations.

Such components include, in the case of ointments, creams, gels, and lotions, white petrolatum, yellow petrolatum, lanolin, bleached beeswax, cetanol, stearyl alcohol, stearic acid, hardened oil, gelled hydrocarbons, polyethylene glycols, liquid paraffin, Bases such as squalane; Solvents and dissolving aids such as oleic acid, isopropyl myristate, glycerin triisooctanoate, crotamiton, diethyl sebacate, diisopropyl adipropyl, hexyl laurate, fatty acids, fatty acid esters, aliphatic alcohols and vegetable oils; Antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene and butylhydroxyanisole; Preservatives such as parahydroxybenzoic acid ester; Moisturizing agents such as glycerin, propylene glycol and sodium hyaluronate; Surfactants such as polyoxyethylene derivative, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester and lecithin; Thickeners such as carboxyvinyl polymer, xanthan gum, carboxymethyl cellulose, carboxymethyl cellulose sodium salts, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and the like.

In the case of aerosols, white petrolatum, yellow petrolatum, lanolin, bleached beeswax, cetanol, stearyl alcohol, stearic acid, used in the preparation of ointments, creams, gels, suspensions, emulsions, solutions and lotions Bases such as hardened oil, gelled hydrocarbon, polyethylene glycol, liquid paraffin, squalane and the like; Such as oleic acid, isopropyl myristate, diisopropyl adipic acid, isopropyl sebacate, glycerin triisooctanoate, crotamiton, diethyl sebacate, hexyl laurate, fatty acids, fatty acid esters, aliphatic alcohols, vegetable oils Solvents and dissolution aids; Antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene and butylhydroxyanisole; Preservatives such as parahydroxybenzoic acid ester; Moisturizing agents such as glycerin, propylene glycol and sodium hyaluronate; Surfactants such as polyoxyethylene derivatives, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, lecithin; Thickeners such as carboxyvinyl polymer, xanthan gum, carboxymethyl cellulose, carboxymethyl cellulose sodium salts, hydroxypropyl cellulose, hydroxypropyl methyl cellulose; In addition, various stabilizers, buffers, mating agents, suspending agents, emulsifiers, fragrances, preservatives, dissolution aids, and other suitable additives may be blended.

Moreover, a stabilizer, a preservative, an absorption promoter, a pH adjuster, and other suitable additives can be mix | blended as needed.

In the case of a shampoo, any one or more of a synthetic surfactant, a preservative, a thickening agent, a viscosity adjusting agent, a pH adjusting agent, a perfume, a dye, a hair conditioner, and water, which are cleaning components, may be contained. Among the synthetic surfactants, synthetic anionic surfactants are alkyl and alkyl ether sulfates, and representative examples thereof include sodium lauryl sulfate, lauryl ammonium sulfate, lauryl sulfate triethanolamine, polyoxyethylene lauryl sulfate, polyoxyethylene lauryl ammonium sulfate, and the like. have. Among the synthetic surfactants, synthetic amphoteric surfactants are alkyl betamin and alkyl amidopropyl betaine, and representative examples thereof are cocodimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, lauryl dimethyl alpha-carboxyethyl betaine. , Cetyl dimethyl carboxymethyl betaine, cocamidopropyl betaine and the like. The nonionic surfactants include alkanol amides and amine oxides, such as lauryl diethyl amine oxide, palm oil alkyldimethyl amine oxide, lauric acid diethanolamide, palm oil fatty acid diethanolamide, palm oil fatty acid monoethanolamide, and the like.

The optional ingredients used in the present invention are well known to those skilled in the art as conventional optional ingredients for maintaining basic physical properties and quality as shampoos. Such optional ingredients include pearlescent aids, preservatives, thickeners and viscosity adjusting agents, pH adjusting agents, perfumes, dyes, hair conditioning agents. Pearlescent aids such as, for example, ethylene glycol monostearate, ethylene glycol distearate; Preservatives such as methyl paraoxycyanate, methylchloro isothiazolinone and a mixture of methyl isothiazolinone; Thickeners and viscosity modifiers such as sodium chloride, ammonium chloride, propylene glycol; PH adjusters such as citric acid, phosphoric acid, sodium hydroxide, potassium hydroxide; Dyestuffs such as polyquaternium-10, polyquaternium-7, methylpolysiloxanes, dimethiconecopolyols, hair conditioning agents such as hydrolyzed animal proteins, water soluble tars are used, and fragrances may also be used.

Hair to which the composition of the present invention is applied includes hair follicles and hair follicles of the head, hair and eyelashes, and eyelashes, beards, armpits, pubic hair, and all parts of the hair root and hair follicles throughout the body.

The composition of the present invention may also be a pharmaceutical composition, a quasi-drug composition, a cosmetic composition.

When the composition of the present invention is a pharmaceutical composition, it may be applied by topical application by parenteral administration or application.

The suitable dosage of the pharmaceutical composition of the present invention may vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration, and the duration, and may be appropriately selected by those skilled in the art. .

When the composition of the present invention is a cosmetic composition, it may contain auxiliary agents commonly used such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, fragrances, fillers, blocking agents, pigments, odorants and dyes. Can be.

In one embodiment, the cosmetic composition is an external preparation for skin, hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder gel, hair pack, hair treatment, eyebrow hair regrowth , Eyelash regrowth, eyelash nutritional preparations.

In addition, the hair loss preventing composition of the present invention can be used for pets differently from the formulation. For example, it can be prepared in various forms such as solution, sol-gel, emulsion, oil, wax, aerosol, etc. such as pet shampoo and pet rinse. It can be prepared by addition.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

Example 1

To confirm the efficacy of the polypeptide comprising the amino acid sequence of SEQ ID NO: 1 poly R ₈ (RRRRRRRR) and polyglycine linker (GGGG) at the amino acid terminal of SEQ ID NO: 1 and lysine and FITC (fluorescent staining at the carboxyl terminus) fluorescein isothiocyanate) was synthesized for appending _{PolyR 8 -HFAP (Hair follicle activating peptide} ) peptides.

PolyR ₈ -HFAP: RRRRRRRRGGGGRKTGHQICKFRKCK- (FITC)

Experimental Example 1

In order to confirm the hair growth promoting effect of the peptide synthesized in Example 1, the hair of the back part of the 7-week-old C3H mouse that entered the resting period was removed, and in the control area, the vehicle (50% ethanol, 20% propylene) was removed. Lycol, 30% water), the treated group was applied once daily for 25 days with 50 μl of peptide and VPA dissolved at 40 mM and 500 mM concentration, respectively. As a result, it was found that the growth of hair was promoted in the group treated with VPA and peptide, compared to the control group. In particular, the growth of hair was significantly increased in the group treated with peptide. (Figure 1)

Experimental Example 2

The skin tissue of the mouse experimented in FIG. 1 was immersed in 4% paraformaldehyde and fixed, embedded in paraffin, and sliced into 4 μm thick. The delaminated tissues were deparaffinized and rehydrated and stained with hematoxylin (purple) and eosin (pink) to observe histological structures. As a result of observing the microscope, it was confirmed that the hair follicles in the growth phase were found in the group treated with the peptide and VPA compared to the control group. (Figure 2)

Experimental Example 3

From the tissue staining results obtained in FIG. 2, more than 50 hair follicles were observed per mouse to calculate the ratio of hair follicles in the growth phase among the whole hair follicles. As a result, it was confirmed that the ratio was significantly increased in the group treated with peptide or VPA. In the case of peptides, the proportion of growing hair follicles was increased by three times compared to VPA. (Figure 3)

Experimental Example 4

The skin tissue flakes used in FIG. 2 were deparaffinized and rehydrated and then heated in 121 mM Celsius buffer for 15 minutes to regenerate antigenicity. Blocking flakes with albumin to prevent nonspecific antigen-antibody reactions, epidermal differentiation markers known to increase in growing hair, loricrin, filaggrin, keratin 14 ) Antibodies were treated to induce antigen-antibody responses. Again, the antibody was recognized as an antigen, and the secondary antibody bound to the fluorescent material was treated on the flake to induce an antigen-antibody reaction, and the result was observed through a fluorescence microscope. As a result, it was confirmed that the expression of these epidermal differentiation markers was significantly increased in the skin tissue treated with the peptide. (Figure 4)

<110> Yonsei University Industry-Academic Cooperation Foundation <120> Composition for prevention, treatment, or improvement of hair          loss <130> P121158 <160> 7 <170> KopatentIn 2.0 <210> 1 <211> 13 <212> PRT <213> human <400> 1 Arg Lys Thr Gly His Gln Ile Cys Lys Phe Arg Lys Cys   1 5 10 <210> 2 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> PolyR8 <400> 2 Arg Arg Arg Arg Arg Arg Arg Arg Arg   1 5 <210> 3 <211> 11 <212> PRT <213> Artificial Sequence <220> HIV-Tat <400> 3 Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg   1 5 10 <210> 4 <211> 34 <212> PRT <213> Artificial Sequence <220> <223> HSV VP22 <400> 4 Asp Ala Ala Thr Ala Thr Arg Gly Arg Ser Ala Ala Ser Arg Pro Thr   1 5 10 15 Glu Arg Pro Arg Ala Pro Ala Arg Ser Ala Ser Arg Pro Arg Arg Pro              20 25 30 Val glu         <210> 5 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Antp <400> 5 Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys   1 5 10 15 <210> 6 <211> 21 <212> PRT <213> Artificial Sequence <220> <223> Transpartan <400> 6 Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu Lys Ala Leu Ala Ala Leu   1 5 10 15 Ala Lys Lys Ile Leu              20 <210> 7 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> PolyR8-HFAP <400> 7 Arg Arg Arg Arg Arg Arg Arg Arg Arg Gly Gly Gly Gly Arg Lys Thr Gly   1 5 10 15 His Gln Ile Cys Lys Phe Arg Lys Cys              20 25

Claims (12)

A pharmaceutical composition for preventing or treating alopecia comprising a polypeptide consisting of 25 to 55 amino acids comprising the amino acid sequence of SEQ ID NO: 1 and a protein transduction domain (PTD) sequence linked thereto. delete The method of claim 1, wherein the PTD (protein transduction domain) is poly R ₈ , HIV-Tat, HSV VP22, Antp or Transportan selected from the group consisting of SEQ ID NOs: 2-6 Composition. The pharmaceutical composition for preventing or treating alopecia of claim 1, wherein the linkage between the amino acid sequence of SEQ ID NO: 1 and the PTD sequence is by a linker. The method of claim 1, wherein the alopecia is alopecia areata, hereditary androgen alopecia, resting alopecia, traumatic alopecia, hair growth wall, pressure alopecia, growth alopecia, nasal alopecia, syphilis alopecia, seborrheic alopecia, symptomatic alopecia, scarring alopecia. Or or alopecia areata selected from the group consisting of a pharmaceutical composition for preventing or treating alopecia. The pharmaceutical composition for preventing or treating alopecia of claim 1, wherein the pharmaceutical composition has a formulation of a cream, lotion, aerosol, shampoo, gel, or pack. A cosmetic composition for improving alopecia comprising a polypeptide consisting of 25 to 55 amino acids comprising the amino acid sequence of SEQ ID NO: 1 and a PTD (protein transduction domain) sequence linked thereto. delete According to claim 7, wherein the PTD (protein transduction domain) is poly R ₈ selected from the group consisting of SEQ ID NO: 2, HIV-Tat, HSV VP22, Antp or Transportan cosmetic composition for improving alopecia. The cosmetic composition for improving alopecia of claim 7, wherein the amino acid sequence of SEQ ID NO: 1 and the PTD sequence are linked by a linker. According to claim 7, wherein the alopecia is alopecia areata, hereditary androgen alopecia, resting alopecia, traumatic alopecia, hair growth wall, pressure alopecia, growth alopecia, nasal alopecia, syphilis alopecia, seborrheic alopecia, symptomatic alopecia, scarring alopecia Or or alopecia areata cosmetic composition for improving at least one selected from the group consisting of alopecia areata. According to claim 7, wherein the cosmetic composition is an external preparation for skin, hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder gel, hair pack, hair treatment, eyebrow A cosmetic composition for improving alopecia having a formulation of a hair regrowth, eyelash regrowth, and eyelash nourishing agent.

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