WO1987007505A1 - Wound-healing drug and cosmetics - Google Patents

Wound-healing drug and cosmetics Download PDF

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Publication number
WO1987007505A1
WO1987007505A1 PCT/JP1987/000364 JP8700364W WO8707505A1 WO 1987007505 A1 WO1987007505 A1 WO 1987007505A1 JP 8700364 W JP8700364 W JP 8700364W WO 8707505 A1 WO8707505 A1 WO 8707505A1
Authority
WO
WIPO (PCT)
Prior art keywords
wound
hair
skin
therapeutic agent
cosmetic
Prior art date
Application number
PCT/JP1987/000364
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
Masakazu Adachi
Original Assignee
Japan Immuno Research Laboratories Co., Ltd.
Otsuka Pharmaceutical Co., Ltd.
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 Japan Immuno Research Laboratories Co., Ltd., Otsuka Pharmaceutical Co., Ltd. filed Critical Japan Immuno Research Laboratories Co., Ltd.
Priority to DE8787903751T priority Critical patent/DE3781662T2/de
Priority to GB8801959A priority patent/GB2200282B/en
Priority to NL8720257A priority patent/NL8720257A/nl
Publication of WO1987007505A1 publication Critical patent/WO1987007505A1/ja
Priority to DK072188A priority patent/DK167997B1/da

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81Protease inhibitors
    • C07K14/8107Endopeptidase (E.C. 3.4.21-99) inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Definitions

  • the present invention relates to a wound healing agent, a hair follicle> a cosmetic, and more particularly, to a wound healing agent characterized by containing ovamacroglobulin as an active ingredient.
  • the present invention relates to pharmaceuticals or cosmetics.
  • compounds that can be used for the treatment of wounds include retinoic acid, allantoin, asiaceous icoside (Aciaceae), and asia at icosi de. ⁇ etc. are known. And force, while these drugs are displaced also for the stomach 0 or even still be sufficiently exhibit the action of promoting the granulation and the like, scan terrorism Lee de system during thermal wounds, non-scan terrorist Lee de It is known that the use of anti-inflammatory drugs in the system rather abolishes the resistance]. However, when these drugs are administered, it is necessary to use them in combination with drugs that can activate and enhance the resistance. Is done.
  • a drug that has recently been effective in treating wounds it is isolated from mammalian body fluids and has a molecular weight of about 5300 and is composed of 52 amino acids.
  • Japanese Patent Application Laid-Open No. 57-37871 16 compositions containing essential amino acids
  • an egg containing iodine at a high degree of 300 U above 300 U ⁇ has been proposed to promote wound treatment and reduce muscular disease. It is effective for prevention (Japanese Patent Application Laid-Open No. 59-116162), and a skin cosmetic comprising dried egg white as a base for skin cosmetics (Japanese Patent Publication No. Sho 61-125) No.
  • the inventors of the present invention have studied diligently, Gogo and Oboma globulin, which have excellent wound healing promotion effects, hair growth promotion effects, skin protection effects, and the like. Wound healing agent, hair restorer, hair restorer with excellent action The present inventors have found that hair fly plans and cosmetics can be obtained, and have completed the present invention.
  • the object of the present invention is to provide a wound treatment agent, hair fly plan, cosmetics, etc. containing omaclog ⁇ -brin as an active ingredient.
  • Another object of the present invention is to provide a method for treating a wound, which is characterized by applying Ovo macroglobulin to an affected area.
  • Still another object of the present invention is to provide a hair growth promoting method characterized by applying ovomacroglobulin to scalp and hair. .
  • Still another object of the present invention is to provide a skin protection method characterized by applying Oboma Gloprolin to the skin.
  • Fig. 1 is a graph showing the change in body weight of a test mouse in a burn recovery test using a burn wound mouse.
  • Fig. 2 is an inflammatory model to which the therapeutic agent of the present invention was applied.
  • Fig. 3 is a drawing showing a cross-section of the mouse group after the injury ⁇ day]), and Fig. 3 is a drawing showing a cross-sectional view of the control mouse to which the hydrophilic ointment was administered.
  • FIG. 4 is a drawing showing the appearance of a wounded part of a mouse with a burn wound to which the therapeutic agent of the present invention has been applied 6 days later
  • FIG. 5 is a drawing showing the appearance of the wounded part of a mouse with a control group.
  • FIG. 6 shows a burn-injured mouse to which the therapeutic agent of the present invention was applied.
  • Drawing showing the cross section of the tissue 4 days after the injury to the patient
  • Fig. 7 is a drawing showing the new surface of the mouse in the control group o
  • FIGS. 8 and 9 are drawings showing the appearance of the useful part of the skin-injured mouse to which the therapeutic agent of the present invention was applied 7 days after the injury.
  • D »FIG. 10 O is the mouse in the control group. It is a drawing showing the appearance of the damaged part o
  • Fig. 11 and Fig. 12 are drawings showing the appearance of the injured area of the wounded mouse on which the therapeutic agent of the present invention was applied 21 days after the injury.
  • Fig. 13 is a mouse in the control group. O This is a drawing showing the external appearance of the damaged part o
  • FIG. 14 is a drawing showing extension of corneal epithelial cells.
  • FIG. 15 is a drawing showing a tissue section of a periodontal tissue-injured mouse to which the therapeutic agent of the present invention was applied 7 days after the injury! ),
  • Fig. 16 is a drawing showing the cross section of the mouse of the control group o The best mode for carrying out the invention
  • wound treatment agent of the present invention examples include: ? Wound, cut! ) Wounds, burns, burns, frostbite, skin ulcers, dry skin, skin; * keratosis, cracks, redness, dermatitis, sores of athlete's foot, surgical wounds, corneal wounds, and hemorrhoids : 1 $, remedy for wounds including pressure sores etc.)
  • For cosmetics apply to the skin, for example, after shaving D, after using a depilatory cream, after using a detergent, etc.)), or apply to skin with rough skin, for example. It has excellent skin protection and improvement effects, and Sensitive, E mode Li E down shea one against KawaIsao while ⁇ a smooth feeling like: Application Benefits Conclusions zone preparative Ko ⁇ , affinity etc. remarkable and tool - can be improved 'and also - stimulation to KawaIsao Cosmetic water V Cosmetics, liquids, vans, skin cosmetics in the form of dae-yeon, etc. and, for example, Chan 7 °, skin, hair liquid, Scalp, hair scalp and other scalp; various forms of hair and cosmetics applied to sashimi
  • the agent for treating wounds, hair follicles and cosmetics of the present invention which is required to contain as an active ingredient, it is essential that it contains McLogbrin, and Macuglin is egg white. Is known as a glycoprotein poverty that exists in the United States.]
  • the method of preparing the services is already known. [Finy (Feen.yB-E.) Et al. Biochemistry-And 'Fisher, 1st Corap.Bi 0 chem.Pliy »i» 1.), 5' 4r A, 28 1 1 9 7 6) J.
  • Examples of a method for obtaining ovomacroglobulin from egg white include mixing egg white with a water-soluble solvent such as a tris-hydrochloric acid buffer solution, or mixing the egg white with a water-soluble solvent. After removing insoluble proteins such as opomucine by adding a gel to the gel, the gel may be filtered. Ovomacroglobulin can be obtained as a glycoprotein 0
  • the therapeutic agent of the present invention can be used to prepare a monophasic medical preparation according to a known method, except that the above-obtained glomacrin globulin obtained as described above is blended as an active ingredient.
  • O The preparation can be prepared.
  • O The form of the pharmaceutical preparation can be appropriately selected from various forms according to the intended use of the obtained preparation. Examples of the form include liquid coating agents, lotions, aerosols, and linear agents.
  • Ointments Injectables such as pills 3 ⁇ 4
  • suppositories Examples of preparations for local administration such as injections etc.0
  • Diluents 1 Excipients and the like can be used as appropriate.
  • an ordinary hydrophobic or hydrophilic base such as fat, Fatty oils, lanolin, decelin, raffin, roux '' Glycols, high-grade alcohols, glycerin, water, etc.
  • the above-mentioned external preparations may contain various additives which are known to be usually added as needed, for example, stabilizers, fragrances, 1 colorants, etc. 0
  • the amount of the active ingredient to be contained in the therapeutic agent of the present invention i.e., the amount of Biamacroglobulin is not particularly limited and may be appropriately selected from a wide range.
  • the therapeutic agent in the form status of 3 ⁇ 4 formulation, the active ingredient content in the formulation, determined this age I sex and other conditions of the patient to be applied, by Ji fS on the degree of diseases and the like for example, a therapeutic agent in the form of an external preparation can be applied to the affected area one or more times a day by spraying, applying, or the like in an amount sufficient to reach the entire affected area. it can.
  • hair fly medicine For example, it can be applied to hair and scalp 0
  • Ovomaclog Mouth Brine When used as a cosmetics department, it is the same as ordinary cosmetics except that Ovomaclog Mouth Brine is contained as an active ingredient.
  • various forms as described above for example, lotion as a cosmetic applied to the skin, various forms such as cream 1 liquid solution foundation, and for example, Chambers / Rinses * Hair liquids, set-downs, etc.
  • Various forms applicable to scalp or hair such as tonic o
  • the preparation into these various forms can be carried out according to a conventional method.
  • various known cosmetic bases and, if necessary, various incense, antioxidants, surfactants The same applies to the use of additives such as preservatives.
  • the amount of ovomacroglobulin in the cosmetic can be appropriately selected depending on the form of the obtained cosmetic, the desired effect, and the like. 0 1 to 30% by weight >> Preferably, the amount should be in the range of about ⁇ ⁇ ⁇ ⁇ ⁇ to about 1% by weight ⁇
  • Tri using casein as a substrate 7 ° cin inhibition activity was determined by the method of Kitamoto et al. [T. Kitam. to, ⁇ .
  • the active fraction obtained in the next step was reduced using a Pelicon cassette (MilliAria) equipped with a molecular sieve membrane l OOO OO, and a 5 m -The buffer was exchanged with hydrochloric acid buffer solution (pH 77). O The sample obtained was replaced with a 1 Om tris-salt buffer solution (pH 7) containing 1 OmM NaCZ. 7) DEAE triacyl M equilibrated in
  • Test is 0, ie, I j?
  • body weight 2 0 0 to 2 5 0 of the window office Turn-male rats 0 each group La, which were divided into five or we made two groups each group After shaving the hair of the target site along the midline on the back of each of the kits with a parican, one of them was cut into a circular shape with a diameter of 1 by an electric iron (scale temperature 100 to 110). (° C) for 20 seconds to create a burn site. The other was left as a non-burn site o
  • Q 5% Evans' Blue dye was intravenously administered to the rats in each group.30 minutes after that, that is, 48 hours after the burn was made, The rat was exsanguinated and killed, and the skin at the burn site and the non-burn site was removed, and the fat adhered was removed.
  • the absorbance of the obtained supernatant was measured at a wavelength of 62 nm by a spectrophotometer.] Measured o Measured absorbance by the standard curve prepared beforehand. O The amount of blue was calculated.o This value was shown as the average soil standard error.o
  • mice were divided into 5 groups of 4 animals per group.
  • the following four groups of mice were subjected to a total of four times each of the following softener samples on the day when the skin inflammation was created, and on the next day k3 and 6
  • Experimental group 1 Hydrophilic ointment of Japanese Pharmacopoeia (Yoshida Pharmaceutical Co., Ltd.)
  • Experimental group 2 Obamacro log ⁇ brin ⁇ ⁇ ⁇ %
  • the remaining one group was treated as a control group without any treatment.
  • the experimental groups 2 to 4 (the group to which the ointment containing oomacroglobulin was applied) had better control of the epidermis than the control group and the experimental group 1 because the inflammation of the dermis and hair follicles was well suppressed.
  • An electric iron set at 400 (»-27» paraffin cutting / melting iron * made by Takashima Shoten) was applied for about 5 seconds to burn.
  • Experimental group 1 Japanese Pharmacopoeia hydrophilic ointment (Yoshida Pharmaceutical Co., Ltd.)
  • Fig. ⁇ The results of the weight change measurement in the above test are shown in Fig. ⁇ .
  • the figure shows the results of each group daily up to 4 days, with the day when the burn was caused by the electric iron as “Day 0”.
  • Animal body The weight change ratio (the average weight before burn injury is set to “1” and the weight change instruction for this) is displayed.
  • the horizontal axis indicates the number of days (days) and the vertical glaze indicates the weight change ratio.
  • Middle Experimental group 4 (Ointment coated with o-macroglobulin ⁇ ⁇ ⁇ ! ⁇ %); (2) Experimental group 1 (Ovomacroglobin without ⁇ -brin added hydrophilicity) Ointment applied group) and (3) indicate control group 0
  • the above weight change reverses the degree of the burn well. That is, after the burn is injured, the vascular permeability is increased due to local inflammation. ? Edema, and therefore, the drowsiness increases according to the size of the burn area, and the weight increases ⁇
  • Hydrophilic petrolatum base 80 Hydrophilic petrolatum base 80
  • the corneal pieces obtained on * were cultured for 28 hours in a culture solution dissolved at U.f / mi »or 0t 5iZm £, 5 ⁇ ? ZW at each temperature. After culturing, the tissue was fixed with 5% glacial acetic acid (95% ethanol), embedded in raffin, and 4 ⁇ sections were prepared.o This was subjected to normal HE staining Then, the length of the corneal epithelial cells that had been observed and extended under a microscope was measured.
  • FIG. 8 Ovomacroglobulin promoted the extension of corneal epithelial cells in a volume-dependent manner.
  • A represents the control group containing only TC-199 culture solution.
  • Show, B is the same as the above culture solution.
  • Macroglobulin 0.05 Z ⁇ , C is Q5? / n and D include 5 # / « ⁇ , respectively.
  • Wounds were formed in the rat periodontal tissue by the following methods 1 and 2, and the therapeutic effect of the therapeutic agent of the present invention was examined.
  • Fig. 15 is a photograph showing the cross section of the structure of the group coated with 0.05% Obomaclog ⁇ -purine-containing paste.
  • Collagen fibers were changed by azane staining ⁇
  • control group In HE staining, the control group is located near and around the wound.
  • the collagen fibers around the wound were ruptured, degenerated, etc., whereas the collagen applied near the wound in the group to which the external preparation of the present invention was applied was torn, but the tears were around the wound.
  • ⁇ ⁇ ⁇ % Ovo macroglobulin-containing paste is more likely to spread ⁇ ⁇ O 5 o / 0 Ovo macrolog mouth Brine-containing paper The tendency was stronger than that of the group with the applied ⁇ .
  • Formulation 3 Cosmetic formulation of the present invention
  • Vitanlauric acid monoester Ovomacroglobulin aoo 5 parts Gumethylamino mouth t? Lulanolic acid ama ao 4 parts
  • Flavors and dyes qs Add water to make the total amount 1 O O
  • ovamacroglobulin, methylaminopropyl lanolinic acid amide, sulfate, and glycerin are referred to.
  • I prepared a homogeneous mixture by adding water.
  • O After dissolving the fragrances, dyes and preservatives in ethyl alcohol >> ⁇ Roxyxylene A uniform mixture was prepared by adding monoester of rubitan-lauric acid, and the homogeneous mixture prepared above was added thereto under vigorous stirring and passed.
  • the skin lotion of the present invention was obtained.o
  • a skin lotion of the present invention was obtained in the same manner as in Formulation Example 3 except that the amount of globulin added was changed to ⁇ part. 0
  • Formulation Example 5 Formulation of the wound treatment agent of the present invention
  • Distilled water was added to the above-mentioned ovomacroglobulin, preservative and fragrance to make the total amount lOOW, and then sterilized to prepare a wound treatment agent of the present invention in the form of a solution for use in olive oil.
  • Prescription Kiyoshi 6 Formulation of the wound treatment agent of the present invention
  • Formulation Example 7 Formulation of the wound treatment agent of the present invention '' Preparation of hydrophilic cartilage
  • the obtained therapeutic agent of the present invention when used as a wound therapeutic agent, it has an excellent effect on promoting wound healing as described above. Demonstrate excellent results o
  • the therapeutic agent of the present invention when used as a hair restorer or a hair restorer, it has an effect of promoting hair growth, and also has an effect of protecting and improving hair, for example, eliminating roughness of hair and improving gloss and the like.
  • the therapeutic agents and cosmetics of the present invention are also excellent in their storage stability and safety.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Birds (AREA)
  • Immunology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
PCT/JP1987/000364 1986-06-13 1987-06-09 Wound-healing drug and cosmetics WO1987007505A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE8787903751T DE3781662T2 (de) 1986-06-13 1987-06-09 Wundheilende arzneimittel und kosmetika.
GB8801959A GB2200282B (en) 1986-06-13 1987-06-09 Wound treating agent and cosmetic
NL8720257A NL8720257A (nl) 1986-06-13 1987-06-09 Wondbehandelingspreparaat en kosmeticum.
DK072188A DK167997B1 (da) 1986-06-13 1988-02-12 Saarbehandlingsmiddel, haarpraeparat og kosmetisk middel

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP61/138670 1986-06-13
JP13867086 1986-06-13
JP62/136516 1987-05-29

Publications (1)

Publication Number Publication Date
WO1987007505A1 true WO1987007505A1 (en) 1987-12-17

Family

ID=15227374

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1987/000364 WO1987007505A1 (en) 1986-06-13 1987-06-09 Wound-healing drug and cosmetics

Country Status (3)

Country Link
JP (3) JPS63107912A (ko)
KR (1) KR940003055B1 (ko)
WO (1) WO1987007505A1 (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2271507A (en) * 1992-09-04 1994-04-20 Summit Technology Ireland Bv Compositions containing plasmin activity inhibitors

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58121220A (ja) * 1982-01-13 1983-07-19 Green Cross Corp:The 寒冷不溶性グロブリンの製造法
JPS5976007A (ja) * 1982-10-22 1984-04-28 Shiseido Co Ltd 化粧料

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58121220A (ja) * 1982-01-13 1983-07-19 Green Cross Corp:The 寒冷不溶性グロブリンの製造法
JPS5976007A (ja) * 1982-10-22 1984-04-28 Shiseido Co Ltd 化粧料

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0274532A4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2271507A (en) * 1992-09-04 1994-04-20 Summit Technology Ireland Bv Compositions containing plasmin activity inhibitors

Also Published As

Publication number Publication date
JPS63107912A (ja) 1988-05-12
JPH0529333B2 (ko) 1993-04-30
KR940003055B1 (ko) 1994-04-13
JPH05306234A (ja) 1993-11-19
JPH05246884A (ja) 1993-09-24
JPH0669958B2 (ja) 1994-09-07
JPH0672086B2 (ja) 1994-09-14
KR880013570A (ko) 1988-12-21

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