WO2008026349A1 - Agent thérapeutique destiné au traitement de l'effluvium télogène - Google Patents

Agent thérapeutique destiné au traitement de l'effluvium télogène Download PDF

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Publication number
WO2008026349A1
WO2008026349A1 PCT/JP2007/059096 JP2007059096W WO2008026349A1 WO 2008026349 A1 WO2008026349 A1 WO 2008026349A1 JP 2007059096 W JP2007059096 W JP 2007059096W WO 2008026349 A1 WO2008026349 A1 WO 2008026349A1
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WO
WIPO (PCT)
Prior art keywords
therapeutic agent
alopecia
resting
partial peptide
agent according
Prior art date
Application number
PCT/JP2007/059096
Other languages
English (en)
Japanese (ja)
Inventor
Satoshi Itami
Yasuyuki Sumikawa
Original Assignee
Juridical Foundation Osaka Industrial Promotion Organization
Osaka University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Juridical Foundation Osaka Industrial Promotion Organization, Osaka University filed Critical Juridical Foundation Osaka Industrial Promotion Organization
Priority to JP2008531975A priority Critical patent/JP5051471B2/ja
Publication of WO2008026349A1 publication Critical patent/WO2008026349A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/2264—Obesity-gene products, e.g. leptin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia

Definitions

  • the present invention relates to a therapeutic agent for resting alopecia, and more specifically to a therapeutic agent for resting alopecia containing lebutin or a partial peptide thereof as an active ingredient.
  • Hair is distinguished from head hair, eyebrows, eyelashes, beards, eyelashes, pubic hairs, body hairs, and the like, depending on the site.
  • the structure is common, and a single hair grows in the hair matrix of the root of the root by the cell division, and a new hair component is born and grows, and is supported by the inherent epithelial hair follicle that envelops it. Fixed.
  • Hair growth in the scalp is not caused continuously, but is caused by an active cycle in which the period of growth and rest is alternately repeated.
  • This cycle is mainly divided into three stages: the growth period, the regression period, and the rest period, and this is called the hair cycle.
  • Growth is the developmental stage of the cycle, characterized by deep penetration of hair follicles into the dermis, rapid proliferation and differentiation of cells to form hair.
  • the next stage is the regression phase, which is a transitional stage characterized by the termination of cell division, during which the hair follicles regress in the dermis and the hair growth stops.
  • the next quiescent phase is characterized as a quiescent phase, during which the regressed hair follicle has a hair root in close proximity to the dermal papillary cell population. Thereafter, cells rapidly grow in the hair root, the dermal papilla expands, the basement membrane components become assimilated, and a new growth phase begins. By the way, if sufficient growth is not maintained and the diapause is shifted to the resting phase, so-called resting alopecia occurs.
  • Patent Document 1 Special Table 2004-519488
  • An object of the present invention is to provide a drug useful for treating resting alopecia (especially male pattern alopecia) by inducing the growth phase from the resting phase of the hair cycle.
  • the present invention provides:
  • a therapeutic agent for resting alopecia characterized by containing levtin or a partial peptide thereof as an active ingredient
  • a method for treating resting alopecia characterized by administering a therapeutically effective amount of levbutin or a partial peptide thereof to a patient with resting alopecia,
  • the therapeutic agent for alopecia alopecia according to the present invention can be administered to humans to induce the hair cycle from the resting phase to the growing phase to treat resting alopecia.
  • FIG. 1 is a photograph showing a hair cycle (A) and a hair follicle state of a 35-day-old (growth stage) of dbZdb mice or normal mice.
  • B represents a normal mouse and C represents a dbZdb mouse.
  • FIG. 2 shows photographs of the 14th day after back hair removal of obZob mice or normal mice at 7 weeks of age (second resting stage) and the hair follicle state of obZob mice or normal mice.
  • a and B are normal mice, and C and D are obZob mice.
  • Figure 3 is a photograph of the dorsal part of the 16th day of ob / ob mice administered with saline or leptin.
  • A shows a physiological saline-administered mouse
  • B shows a levulin-administered mouse.
  • Figure 4 shows photographs of the hair follicle state on day 21 after administration of normal saline or levutin to 7-week-old normal mice, and photographs of the back of day 21 of normal mice administered with levutin or physiological saline. It is.
  • A shows a saline-administered mouse
  • B shows a lebutin-treated mouse.
  • Above C shows leptin-administered mice and below C shows saline-administered mice.
  • FIG. 5 is a photograph of the dorsal region on the 21st day of a normal mouse in which physiological saline or a partial peptide of lebutin (SEQ ID NO: 4) was administered to a normal mouse 7 weeks old.
  • the active ingredient of the therapeutic agent for alopecia according to the present invention is lebutin or a partial peptide thereof.
  • the leptin according to the present invention may be mouse leptin or human leptin, preferably human leptin.
  • the amino acid sequence of human leptin including the signal peptide (21 amino acids) is shown in SEQ ID NO: 1, and that of mouse is shown in SEQ ID NO: 2.
  • the levtin according to the present invention may be substituted by substitution or addition of several amino acids as long as the levtin function is maintained.
  • the partial peptide of levulin according to the present invention includes a partial peptide containing the levtin active site, that is, a low molecular functional peptide.
  • Specific examples of partial peptides that are preferred in that they are low in antigenicity due to partial peptide strength generated by cleaving with an enzyme originally possessed by an animal (particularly human) that is the origin of levutin include SEQ ID NO: 4 The peptide shown by these is mentioned.
  • the lebutin and the partial peptide of lebutin according to the present invention can be prepared by a conventional method, and commercially available products such as human recombinant leptin (R & D Systems) or partial peptide of human leptin (BRACHEM) should be used. You can also. In the case of production, it can be produced according to conventional methods by genetic engineering techniques. For example, levtin is described as an example as follows, but partial peptides can also be produced according to this. First, the gene coding for levutin (the levulin gene) is converted into a conventional genetic engineering method (eg, Sambrook J., Frisch EF, Maniatis T., Molecular Cloning 2nd edition).
  • a conventional genetic engineering method eg, Sambrook J., Frisch EF, Maniatis T., Molecular Cloning 2nd edition.
  • the leptin gene is preferably a human leptin gene, and its DNA sequence including a sequence encoding a signal peptide is as shown in SEQ ID NO: 3. Then, using the obtained levtin gene, levtin can be produced according to a conventional genetic engineering method.
  • the above plasmid contains, for example, genetic information that can be replicated in the host cell, can be propagated autonomously, can be easily isolated and purified from the host cell force, and functions in the host cell.
  • Preferable examples include those in which a gene encoding lebutin is introduced into an expression vector having a detectable promoter and a detectable marker.
  • an expression vector used for expression in Escherichia coli is an expression vector containing a promoter such as lac, trp, tac and the like, and these are commercially available from Falmacia, Takara Shuzo and the like. If it is necessary to induce further high expression, the gene is encoded upstream of the gene encoding levutin. Bosome binding regions may be linked.
  • ribosome binding region examples include those described in reports by Guarente L. et al. (Cell 20, p543) and Taniguchi et al. (Genetics of Industrial Microorganisms, p202, Kodansha).
  • host cells include prokaryotic or eukaryotic microbial cells, insect cells, or mammalian cells.
  • Escherichia coli and the like can be preferably mentioned from the viewpoint of facilitating large-scale preparation of lebutin.
  • the therapeutic agent of the present invention exhibits an excellent effect in the treatment of resting alopecia.
  • Resting alopecia to which the therapeutic agent of the present invention can be applied includes androgenetic alopecia, postpartum (postpartum) alopecia, alopecia after taking pills, diet, starvation alopecia, pressure alopecia, hypothyroidism Alopecia due to pituitary function, alopecia due to hypoparathyroidism, drug-induced alopecia, seborrheic alopecia, traction alopecia, erosion alopecia, alopecia associated with endocrine disease, Examples include alopecia due to contact dermatitis, and male pattern alopecia is particularly preferable.
  • the therapeutic agent for resting alopecia of the present invention When the therapeutic agent for resting alopecia of the present invention is locally administered externally, it is preferably applied locally or injected subcutaneously.
  • the dose of levbutin or its partial peptide, which is the active ingredient varies depending on the subject's gender, age, weight, and condition (symptoms).
  • the area of the application site is usually about 10 cm 2 , and it is usually about 10 to L000 mg, preferably about 10 to 500 mg per day.
  • the above dose should be applied once or several times a day.
  • the dose of levtin or a partial peptide thereof can be appropriately selected depending on the skin area to be administered, but is usually about 1 to about 10 cm 2 of the area of application site: L000 mg, preferably about 10-100 mg.
  • the frequency of administration is not particularly limited, but it is preferably administered once a day to once every several weeks.
  • the therapeutic agent for alopecia of the present invention is locally administered.
  • dosage forms include semi-solid preparations such as ointments and creams, liquid preparations such as shampoos, rinses and lotions, and tapes when applied locally, and injections when administered subcutaneously locally. Drugs are listed.
  • the formulation method for these dosage forms follows the usual method. However, when these formulations are produced, an appropriate amount of the dosage form according to the formulation form is assumed. Body or additive can be used.
  • a solvent eg, purified water
  • a dispersant eg, Tween 80 (manufactured by Atlas Powder Co., USA), HCO60 (manufactured by Nikko Chemicals), polyethylene glycol, etc. , Carboxymethylcellulose, sodium alginate, etc.), preservatives (methylparaben, propylparaben, benzyl alcohol, etc.), isotonic agents (salt sodium, man-tol, sorbitol, glucose, etc.) can do.
  • a solvent eg, purified water
  • a dispersant eg, Tween 80 (manufactured by Atlas Powder Co., USA), HCO60 (manufactured by Nikko Chemicals)
  • polyethylene glycol etc.
  • preservatives methylparaben, propylparaben, benzyl alcohol, etc.
  • isotonic agents salt sodium, man-tol,
  • Ribosomeization means inclusion of a drug in the interior of a ribosome (that is, a closed vesicle composed of a membrane-assembled lipid and an internal aqueous phase), and levtin or a partial peptide thereof. May be contained in a lipid layer assembled in a membrane form constituting a ribosome, or may be contained in an aqueous phase inside the ribosome.
  • various lipophilic or hydrophilic components can be encapsulated in the lipid membrane and the inner aqueous phase, respectively.
  • Ribosomeization of lebutin or a partial peptide thereof can be performed by a conventional method.
  • lebutin or its partial peptide can be dissolved in a membrane constituent lipid component, mixed with a membrane constituent lipid component in a water-soluble non-volatile organic solvent, dissolved or suspended in an aqueous solution, etc. It can be encapsulated in a lipid membrane or an inner aqueous phase.
  • the therapeutic agent for resting alopecia is obtained by dispersing the ribosomal levtin prepared as described above or a partial peptide thereof in a therapeutic agent base.
  • Examples of the lipid used for ribosome formation include glyceport phospholipid, glyceport glycolipid, sphingophospholipid, sphingoglycolipid, sterols and the like.
  • Examples of the dalycerophospholipid include phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine.
  • Examples of the glyceglycoglycolipid include digalatatosyl diglyceride and galactosyl diglyceride.
  • Examples include phingomyelin, glycosphingolipids include celebrity mouthsides and gandariosides, and sterols include cholesterol and cholesterol hemisuccinate.
  • phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, sphingomyelin, ganglioside, etc. each have two saturated or unsaturated fatty acid ester chains, but the fatty acid (alkanoyl or alkenoyl group) moiety carbon Lipids having a number between 10 and 18 can be used as liposome constituents.
  • alkanoyl or alkenoyl group having 10 to 18 carbon atoms examples include desilyl, undesilyl, lauroyl, tridesilyl, myristoyl, pentadesilyl, noremitoyl, heptadesilyl, stearoyl, and oleoyl groups.
  • lauroyl, Myristoyl, palmitoyl and stearoyl groups Preferably, lauroyl, Myristoyl, palmitoyl and stearoyl groups.
  • the aqueous phase that forms the interior of the ribosome is usually an aqueous sodium chloride solution, buffer solution (phosphate buffer, acetate buffer, etc.), monosaccharide or disaccharide aqueous solution (dulcose aqueous solution, trehalose aqueous solution, etc.). Can be used.
  • Fig. 1A shows the normal hair cycle of mice. [0026] (2) Growth phase induction by hair removal in ob / ob (leptin deficient) mice
  • mice with subcutaneous injection of saline showed no hair growth (A in Fig. 5). From this, it was verified that even in normal individuals, partial peptides induce growth from the resting phase.
  • the therapeutic agent for resting alopecia according to the present invention can be used as a medicament for the treatment of resting alopecia.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Dermatology (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract

La présente invention concerne un agent thérapeutique destiné au traitement de l'effluvium télogène, comprenant une leptine ou un peptide partiel de celle-ci en tant qu'ingrédient actif. L'agent thérapeutique est utile lors du passage de la phase télogène, dans le cycle de la croissance du cheveu, à la phase anagène, pour traiter l'effluvium télogène (par exemple la calvitie hippocratique masculine).
PCT/JP2007/059096 2006-08-31 2007-04-26 Agent thérapeutique destiné au traitement de l'effluvium télogène WO2008026349A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2008531975A JP5051471B2 (ja) 2006-08-31 2007-04-26 休止期脱毛症治療剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006-236849 2006-08-31
JP2006236849 2006-08-31

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WO2008026349A1 true WO2008026349A1 (fr) 2008-03-06

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012133817A1 (fr) * 2011-03-31 2012-10-04 花王株式会社 Composition de vésicule

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004519488A (ja) * 2001-03-08 2004-07-02 ユニバーシティー オブ ケンタッキー リサーチ ファウンデイション ニコチン酸化合物を使用するレプチンレベル増大のための方法

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
JP2004519488A (ja) * 2001-03-08 2004-07-02 ユニバーシティー オブ ケンタッキー リサーチ ファウンデイション ニコチン酸化合物を使用するレプチンレベル増大のための方法

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Title
FRANK S. ET AL.: "Leptin enhances wound re-epithelialization and constituents a direct function of leptin in skin repair", J. CLIN. INVEST., vol. 106, no. 4, 2000, pages 501 - 509, XP003021352 *
GOREN I. ET AL.: "Determination of leptin signaling pathways in human and murine keratinocytes", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 303, no. 4, 2003, pages 1080 - 1085, XP003021353 *
IGUCHI M. ET AL.: "Human follicular papilla cells carry out nonadipose tissue production of leptin", J. INVEST. DERMATOL., vol. 117, no. 6, 2001, pages 1349 - 1356, XP002326576 *
ITAMI T.: "Moshuki no Seigyo Bunshi", IGAKU NO AYUMI, vol. 208, no. 13, 2004, pages 1075 - 1076, XP003021351 *
SANO S. ET AL.: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodelling, but does not affect skin morphogenesis", EMBO J., vol. 18, no. 17, 1999, pages 4657 - 4668, XP003021350 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012133817A1 (fr) * 2011-03-31 2012-10-04 花王株式会社 Composition de vésicule
CN103458866A (zh) * 2011-03-31 2013-12-18 花王株式会社 囊泡组合物
US9694076B2 (en) 2011-03-31 2017-07-04 Kao Corporation Vesicle composition

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JPWO2008026349A1 (ja) 2010-01-14

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