CN-122028928-A - Composition for promoting hair growth or inhibiting, preventing or alleviating hair loss comprising peptide as active ingredient

Abstract

The peptide of the present invention has the activities of promoting proliferation of dermal papilla cells (HFDPC) of hair follicle, activating cell proliferation-related signaling proteins and beta-catenin, up-regulating the expression level of growth factor-related genes, up-regulating the expression level of beta-catenin subgenomic genes, and down-regulating the expression level of alopecia protein DKK-1 in human dermal papilla cells, increasing expression of keratin in Hair Outer Root Sheath Cells (HORSC), enhancing expression of transcription factors involved in cell activation in hair growth stromal cells (HGMC), and promoting differentiation of Hair Follicle Stem Cells (HFSC). Thus, the peptides of the invention are useful for promoting hair growth or for inhibiting, preventing, alleviating or treating hair loss.

Inventors

• Zheng Rongchi
• JIN YINMEI
• LI YINGZHI
• Jin Minxiong
• Ji Hana

Assignees

• 凯尔格恩有限公司

Dates

Publication Date

20260512

Application Date

20240912

Priority Date

20230915

Claims (18)

1. 1. A composition for promoting hair growth or inhibiting, preventing or alleviating alopecia, comprising a peptide comprising the amino acid sequence of SEQ ID NO:1 as an active ingredient.
2. 2. A pharmaceutical composition for preventing or treating alopecia, comprising a peptide comprising the amino acid sequence of SEQ ID No.1 as an active ingredient.
3. 3. The pharmaceutical composition of claim 2, wherein the peptide promotes proliferation of one or more cells selected from the group consisting of Hair Follicle Dermal Papilla Cells (HFDPC), hair Outer Root Sheath Cells (HORSC), and Hair Follicle Stem Cells (HFSC).
4. 4. The pharmaceutical composition according to claim 2, wherein the peptide is in dermal papilla cells (HFDPC) of hair follicles, (I) Activating Akt or ERK signaling proteins; (ii) Up-regulating gene expression of one or more factors selected from the group consisting of basic fibroblast growth factor (bFGF), hepatocyte Growth Factor (HGF), keratinocyte Growth Factor (KGF) and Vascular Endothelial Growth Factor (VEGF); (iii) Activating β -catenin; (iv) Up-regulating gene expression of one or more β -catenin downstream factors selected from the group consisting of LEF-1, c-Myc and cyclin D1, or (V) Down-regulating expression level of alopecia inducing protein DKK-1 (Dickkopf-1).
5. 5. The pharmaceutical composition according to claim 2, wherein the peptide increases the expression of one or more proteins selected from the group consisting of Ha3-II, keratin 5, keratin 14 and keratin 19 in Hair Outer Root Sheath Cells (HORSC).
6. 6. The pharmaceutical composition of claim 2, wherein the peptide increases expression of one or more transcription factors selected from the group consisting of MSX2, HOXC13, and FOXN1 in hair-growing stromal cells (HGMC).
7. 7. The pharmaceutical composition of claim 2, wherein the peptide is in Hair Follicle Stem Cells (HFSCs), (I) Down-regulating expression of one or more stem cell markers selected from the group consisting of CD34, CD133, keratin 15 and LHX2, or (Ii) Up-regulating expression of one or more stem cell differentiation markers selected from the group consisting of alpha-SMA, vimentin, keratin-75, proteoglycan and tubulin-1.
8. 8. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition is a topical formulation.
9. 9. A cosmetic composition for promoting hair growth or preventing or alleviating alopecia, comprising a peptide comprising the amino acid sequence of SEQ ID NO:1 as an active ingredient.
10. 10. The cosmetic composition of claim 9, wherein the peptide promotes proliferation of one or more cells selected from the group consisting of Hair Follicle Dermal Papilla Cells (HFDPC), hair Outer Root Sheath Cells (HORSC), and Hair Follicle Stem Cells (HFSC).
11. 11. The cosmetic composition according to claim 9, wherein the peptide is in dermal papilla cells (HFDPC) of hair follicles, (I) Activating Akt or ERK signaling proteins; (ii) Up-regulating gene expression of one or more factors selected from the group consisting of basic fibroblast growth factor (bFGF), hepatocyte Growth Factor (HGF), keratinocyte Growth Factor (KGF) and Vascular Endothelial Growth Factor (VEGF); (iii) Activating β -catenin; (iv) Up-regulating gene expression of one or more β -catenin downstream factors selected from the group consisting of LEF-1, c-Myc and cyclin D1, or (V) Down-regulating expression level of alopecia inducing protein DKK-1 (Dickkopf-1).
12. 12. The cosmetic composition of claim 9, wherein the peptide increases expression of one or more proteins selected from the group consisting of Ha3-II, keratin 5, keratin 14, and keratin 19 in Hair Outer Root Sheath Cells (HORSC).
13. 13. The cosmetic composition of claim 9, wherein the peptide increases expression of one or more transcription factors selected from the group consisting of MSX2, HOXC13, and FOXN1 in hair-growing stromal cells (HGMC).
14. 14. The cosmetic composition of claim 9, wherein the peptide is in Hair Follicle Stem Cells (HFSCs), (I) Down-regulating expression of one or more stem cell markers selected from the group consisting of CD34, CD133, keratin 15 and LHX2, or (Ii) Up-regulating expression of one or more stem cell differentiation markers selected from the group consisting of alpha-SMA, vimentin, keratin-75, proteoglycan and tubulin-1.
15. 15. The cosmetic composition of claim 9, wherein the cosmetic composition is a topical formulation.
16. 16. The cosmetic composition of claim 9, wherein the cosmetic composition has a dosage form 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 cleansing composition, an oil, a powder foundation, an emulsion foundation, a wax-based foundation, and a spray.
17. 17. The cosmetic composition of claim 9, wherein the cosmetic composition has a dosage form selected from the group consisting of hair tonic, hair cream, shampoo, hair rinse, hair conditioner, hair spray, hair rinse, and gel.
18. 18. A method for promoting hair growth or inhibiting, preventing, alleviating or treating alopecia, the method comprising applying a peptide comprising the amino acid sequence of SEQ ID NO:1 or a composition comprising said peptide as an active ingredient to a subject in need of promoting hair growth or inhibiting, preventing, alleviating or treating alopecia.

Description

Composition for promoting hair growth or inhibiting, preventing or alleviating hair loss comprising peptide as active ingredient Cross Reference to Related Applications The present application claims priority from korean patent application No. 10-2023-012857 filed on 9/15 of 2023, the disclosure of which is incorporated herein by reference in its entirety. Technical Field The present invention relates to a composition for promoting hair growth or inhibiting, preventing or alleviating alopecia, which contains a peptide as an active ingredient. Background Alopecia is a phenomenon in which hair loss occurs excessively due to an increase in the telogen period beyond a normal level or an increase in the number of hair follicles in the telogen period, and is not recovered due to excessive hair loss caused by stress, nutrient deficiency, disturbance of local blood flow, hormones, genetic factors, and the like. In addition to endogenous alopecia (e.g., androgenic alopecia and seborrheic alopecia), exogenous alopecia caused by external factors (e.g., ultraviolet rays or fine particulate matter) is also known. Patients suffering from alopecia complain strongly about the loss of mental stress caused by changes in appearance, rather than the function of the hair (e.g. protection from external stimuli). As a therapeutic agent for alopecia, 5 a reductase inhibitors that convert androgenic testosterone into androgenic Dihydrotestosterone (DHT), such as finasteride or dutasteride, have been developed and approved, and minoxidil, a drug having an effect of promoting hair growth by stimulating hair follicles and increasing blood flow, has also been approved and used. However, 5 a reductase inhibitors are reported to have side effects such as sexual dysfunction, depression, anxiety and gynecomastia relatively frequently, and minoxidil is reported to have cardiovascular side effects such as electrocardiographic abnormality, tachycardia and endocarditis as well, and furthermore minoxidil is known to cause recurrence of hair loss when administration of the drug is stopped. Peptides have a high degree of biocompatibility and, when used as a single active ingredient in pharmaceutical or cosmetic compositions, have fewer side effects than extracts or the like containing the various ingredients. In addition, peptides can be easily degraded and cleared by proteolytic enzymes in the body after the effect of suppressing hair loss is locally exerted, and thus, unlike conventional therapeutic agents, peptides are less likely to cause concerns about side effects. International patent application WO2005082395 discloses a peptide having a hair growth promoting effect by promoting the progress of telogen phase of the hair growth cycle to anagen phase, and korean patent No. 10-2387764 discloses a dimeric peptide derivative having a hair follicle cell proliferation promoting effect. [ Related art literature ] [ Patent literature ] WO2005-082395 Korean patent No. 10-2387764 Disclosure of Invention Technical problem In order to develop an active substance capable of promoting hair growth and having hair growth promoting activity and hair loss inhibitory activity with reduced side effects, the present inventors have made an effort to confirm that the peptide of the present invention promotes proliferation of Human Hair Follicle Dermal Papilla Cells (HHFDPC), activates cell proliferation-related signaling proteins in human hair follicle dermal papilla cells, up-regulates gene expression of growth factors, activates β -catenin, up-regulates expression level of β -catenin downstream genes, down-regulates expression level of hair loss-inducing protein DKK-1. In addition, experiments prove that the peptide of the invention increases the expression of keratin in Hair Outer Root Sheath Cells (HORSC), increases the expression of cell activity related transcription factors MSX2, HOXC13 and FOXN1 in human hair growing stromal cells (HHGMC), promotes proliferation and induces differentiation of Hair Follicle Stem Cells (HFSCs), thereby completing the invention. The object of the present invention is to provide a composition for promoting hair growth or inhibiting, preventing or alleviating alopecia, which comprises a peptide as an active ingredient. It is another object of the present invention to provide a pharmaceutical composition for preventing or treating alopecia, which comprises a peptide as an active ingredient. It is still another object of the present invention to provide a cosmetic composition for promoting hair growth or preventing or alleviating alopecia, which comprises a peptide as an active ingredient. It is still another object of the present invention to provide a method for promoting hair growth or inhibiting, preventing, alleviating or treating alopecia, which comprises applying a peptide or a composition comprising the peptide as an active ingredient to a subject. Technical proposal In one aspect, the present invention provides a compos