# US 11,298,372 B2 · Composition for ameliorating loss of hair and graying of hair, and use thereof

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- Number: US 11,298,372 B2
- Document ID: US11298372B2
- Status: Granted
- Kind: B2
- Application number: 16/885,930
- Filed: 2020-05-28
- Published: 2020-09-17
- Granted: 2022-04-12
- Earliest claimed: 2016-01-12
- Assignees: National University Corporation Tokyo Medical and Dental University
- Applicants: National University Corporation Tokyo Medical and Dental University
- Inventors: Emi Nishimura; Hiroyuki Matsumura
- Web page: https://patentgrep.com/patent/US11298372B2

## CPC

- A61K 31/12: Ketones
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 8/97: from algae, fungi, lichens or plants; from derivatives thereof
- A61K 31/05: Phenols {(cannabinoids A61K31/658)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/16: Amides, e.g. hydroxamic acids
- A61K 31/222: with compounds having aromatic groups, e.g. dipivefrine, ibopamine
- A61K 31/355: Tocopherols, e.g. vitamin E
- A61K 31/375: Ascorbic acid, i.e. vitamin C; Salts thereof
- A61K 31/381: having five-membered rings
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/5415: ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 36/04: Rhodophycota or rhodophyta (red algae), e.g. Porphyra
- A61K 36/05: Chlorophycota or chlorophyta (green algae), e.g. Chlorella
- A61K 36/14: Cupressaceae (Cypress family), e.g. juniper or cypress
- A61K 36/185: Magnoliopsida (dicotyledons)
- A61K 36/23: Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K 36/28: Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K 36/30: Boraginaceae (Borage family), e.g. comfrey, lungwort or forget-me-not
- A61K 36/424: Gynostemma
- A61K 36/47: Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
- A61K 36/48: Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K 36/488: Pueraria (kudzu)
- A61K 36/489: Sophora, e.g. necklacepod or mamani
- A61K 36/53: Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K 36/54: Lauraceae (Laurel family), e.g. cinnamon or sassafras
- A61K 36/577: {Malvaceae (Mallow family)}
- A61K 36/60: Moraceae (Mulberry family), e.g. breadfruit or fig
- A61K 36/718: Coptis (goldthread)
- A61K 36/738: Rosa (rose)
- A61K 36/74: Rubiaceae (Madder family)
- A61K 36/742: {Coffea, e.g. coffee}
- A61K 36/82: Theaceae (Tea family), e.g. camellia
- A61K 38/55: Protease inhibitors
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 45/00: Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 17/14: for baldness or alopecia
- A61Q 5/00: Preparations for care of the hair
- A61Q 7/00: Preparations for affecting hair growth
- C12Q 1/37: involving peptidase or proteinase
- A61K 31/13: Amines {(A61K31/04 takes precedence)}
- A61K 36/00: Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines {(antigens from pollen A61K39/36)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention provides novel compositions for suppressing or improving hair loss, and compositions for suppressing or improving graying. More specifically, it provides agents that stabilize type XVII collagen expression, preferably agents that suppress the degradation of type XVII collagen by ELANE inhibitors and such, and compositions comprising a DNA repair-promoting agent or a DNA damage-suppressing agent as an active ingredient. Advantageous suppressive effects of hair loss and graying can be obtained when a composition comprising as an active ingredient a suppressive agent of type XVII collagen degradation such as an ELANE inhibitor is administered to a mammal. For the ELANE inhibitors, suppressive agents of type XVII collagen degradation and DNA repair-promoting agents, low-molecular compounds, polypeptides, proteins, antibodies, or nucleic acid medicine such as antisense oligos or siRNAs may be used. A method of screening for effective substances for suppression of hair loss and graying is also provided.

## Claims

### Claim 1

A method for suppressing or improving hair graying in a mammal, comprising administering to the mammal a stabilizing agent of type XVII collagen expression, wherein the stabilizing agent of type XVII collagen expression is selected from the group consisting of an MMP inhibitor, an NADPH oxidase inhibitor, an oxidation inhibitor, and an ADAM inhibitor.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the MMP inhibitor is selected from the group consisting of Marimastat, Batimastat, PD166793, Ro32-3555, WAY170523, UK370106, TIMP1, TIMP2, TIMP3, and TIMP4.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the NADPH oxidase inhibitor is selected from the group consisting of apocynin, AEBSF, GK-136901, ML171, VAS2870, and VAS3947.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the oxidation inhibitor is selected from the group consisting of ascorbic acid, edaravone, α-tocopherol, glutathione, catechin, and resveratrol.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the ADAM inhibitor is selected from the group consisting of TAPI-2, Secophenol, GI254023X, Erythrolosamine, TIMP1, TIMP2, TIMP3, and TIMP4.

### Claim 6

A method for suppressing or improving hair graying in a human subject, comprising administering apocynin to the human subject.