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WO2008023818A1 - Fibre et procédé de production de fibre - Google Patents

Fibre et procédé de production de fibre Download PDF

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Publication number
WO2008023818A1
WO2008023818A1 PCT/JP2007/066556 JP2007066556W WO2008023818A1 WO 2008023818 A1 WO2008023818 A1 WO 2008023818A1 JP 2007066556 W JP2007066556 W JP 2007066556W WO 2008023818 A1 WO2008023818 A1 WO 2008023818A1
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WO
WIPO (PCT)
Prior art keywords
fiber
peptide
acid
poly
ester
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2007/066556
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English (en)
Japanese (ja)
Inventor
Yoshiko Abe
Eriko Kusaka
Koji Inagaki
Junichi Kondo
Kazuo Shinmura
Hiroshi Uyama
Kazuo Maeshima
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sekisui Chemical Co Ltd
Original Assignee
Sekisui Chemical 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 Sekisui Chemical Co Ltd filed Critical Sekisui Chemical Co Ltd
Publication of WO2008023818A1 publication Critical patent/WO2008023818A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0092—Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • the present invention is an excellent wound healing promoting action with high drug release and / or bioavailability.
  • the present invention relates to a fiber having an allergic and non-allergic inflammation suppressing action, an immunosuppressing action, an antibacterial action, an antitumor action, a site force-in inducing action, etc.
  • Patent Document 1 discloses novel peptides
  • Patent Document 2 uses such peptides as wound healing agents for healing wounds such as surgical incisions, gastric ulcers, burns, and lacerations. Therefore, it is described that it exhibits a highly useful wound healing effect.
  • Non-Patent Document 1 discloses that the peptide induces the production of transforming growth factor (TGF- / 3), which is a kind of cytodynamic force-in.
  • TGF- / 3 transforming growth factor
  • Patent Document 3 discloses a medical material that contains the peptide or is surface-treated with this peptide. Since such peptides have poor solubility in water, they are hardly soluble, so simply by impregnating fibers such as gauze, non-woven fabric, and absorbent cotton, or by chemical bonding or physical adsorption, There has been a problem that the action and therapeutic effect of the peptide having low drug release and / or bioavailability cannot be fully exhibited.
  • Patent Document 1 JP-A-8-1 19993
  • Patent Document 2 JP-A-9 040576
  • Patent Document 3 Japanese Patent Laid-Open No. 11 178911
  • Non-Patent Document 1 Yoshiko Abe et al., Eur J Pharmacol. 2000 17; 408 (2): 213— 8. Disclosure of the Invention
  • the present invention relates to an excellent wound healing promoting action with high drug release and / or bioavailability, allergic and non-allergic inflammation inhibiting action, immunosuppressing action, antibacterial action, antitumor action, site It is an object of the present invention to provide a fiber having a force-in inducing action and the like and a method for producing the fiber.
  • a peptide represented by the following formula (1) and / or a pharmacologically acceptable salt or ester of the peptide is carried on the surface and / or inside of a carrier fiber having a fiber diameter of 2000 nm or less. Fiber.
  • the present inventors have carried the surface and / or the inside thereof with the peptide represented by the above formula (1) and / or the pharmacologically acceptable salt or ester of the peptide.
  • the action and therapeutic effect of the peptide represented by the above formula (1) and / or the pharmacologically acceptable salt or ester of the peptide are remarkably increased.
  • the present invention has been completed.
  • the peptide represented by the formula (1) and / or a pharmacologically acceptable salt or ester of the peptide is carried on the surface and / or inside of the carrier fiber. It is a thing.
  • the peptide represented by (1) above is obtained by culturing the peptide-producing strain belonging to the genus Streptomyces, for example, Streptomyces nobilis (hereinafter referred to as "S. nobilis").
  • the obtained culture solution or the dried product of the same solution or the extract of the cultured microbial cells extracted with an organic solvent is subjected to various chromatographies, and the column chromatography fraction containing the target product is recrystallized. Can be obtained.
  • Actinomyces S. nobilis for obtaining the above peptides is available from public preservation agencies, for example, the preserved bacteria of RIKEN (JCM4274) (this is ATCC 19252 in the United States and CBS198. Bacteria such as 65) can be used.
  • the fiber of the present invention when the peptide and the pharmacologically acceptable salt or ester of the peptide are used at the same time, or instead of the peptide, the pharmacologically acceptable of the peptide Even when a salt or ester is used, the same effect can be exhibited.
  • Examples of the pharmacologically acceptable salt of the peptide include alkali metal salts such as lithium salt, sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, ammonium salt and the like.
  • Salts with inorganic bases salts with organic bases such as organic amine salts such as triethylamine salts and pyridine salts; inorganic acid addition salts such as hydrochlorides, sulfates and phosphates; acetates and maleates
  • Examples of the pharmacologically acceptable ester of the peptide include, for example, methyl ester, ethyl ester, propyl ester, isopropyl ester, butinoresestenole, isobutyl which may have at least one appropriate substituent.
  • Alkyl esters such as esters, t-butyl esters, pentyl esters, hexyl esters, such as alkanoloxy Cialkyl esters (eg, acetoxymethyl ester, propionyloxymethyl)
  • Alkanesulfonylalkyl esters eg, 2-mesylethyl
  • mono-, di- or trihaloalkyl esters eg, 2-iodoethyl ester, 2, 2, 2-trichloroethyl ester, etc.
  • alkoxycarbonyl Oxyalkyl esters for example, methoxycarbonyloxymethyl ester, ethoxycarbonyloxymethyl ester, 2-methoxycarbonyloxychetyl ester, 1 ethoxycarbonyloxychetilester, 1 isopropoxycarbonyloxychetyl) Esters, etc.
  • At least one Suitable optionally have a substituent ⁇ reel esters (e.g., off-enyl ester, 4 Black mouth Fuenore Estenole, Torinore Estenore, Tobutino Lefu Eneno Este Nore, Xylinole Stell, Mesityl ester, Tamenyl ester, etc.), Phthalidyl ester, etc.
  • a substituent ⁇ reel esters e.g., off-enyl ester, 4 Black mouth Fuenore Estenole, Torinore Estenore, Tobutino Lefu Eneno Este Nore, Xylinole Stell, Mesityl ester, Tamenyl ester, etc.
  • the peptide and / or the pharmacologically acceptable salt or ester of the peptide may be either amorphous or crystalline, but is preferably amorphous. Good.
  • the material of the carrier fiber is not particularly limited, and a water-soluble or water-insoluble polymer, biodegradable or non-biodegradable polymer may be selected according to the purpose of use, application site, and the like.
  • water-soluble polymer examples include poly (ethylene oxide) and polybular alcohol.
  • water-insoluble polymer examples include, for example, polyurethane, poly (ethylene oxide), polyethylene, polypropylene, polylactic acid, polydaricholic acid, polydioxanone, silk, polyamino acid, polyacetate butyl, polychloride butyl, Polyacrylonitrile, polystyrene, poly (methyl acrylate), poly (methacrylic acid), poly (methyl methacrylate), poly (vinylidene chloride), poly (vinylidene fluoride), poly (ethylene terephthalate), poly-strength prolatatone, 6-nylon, 6, 6-nylon, meta-aramid, polyaniline Examples thereof include phosphorus and salts or esters thereof. These may be used alone or in combination of two or more. These copolymers can also be used.
  • the biodegradable polymer is not particularly limited, and for example, starch, gelatin, collagen, polylactic acid, polydaricholic acid, polydioxanone, silk, polyamino acid, alginic acid, hyaluronic acid, chitin, chitosan, and Examples of these salts or esters . These may be used alone or in combination of two or more. These copolymers can also be used.
  • non-biodegradable polymer examples include polyurethane, poly (ethylene oxide), polyvinylenoleole cornole, polyvinylino pyrrolidone, senorelose, hydroxyethinoresenorelose and pinolemethinoresenorelose.
  • the polymer used as a raw material for the carrier fiber includes polyurethane, poly (ethylene oxide), polyvinylinoreconole, polyvinylenopyrrolidone, cellulose, hydroxys, hydroxypropinoremethenoresenorelose phthalate.
  • the upper limit of the fiber diameter of the carrier fiber is 2000 nm. When it exceeds 2000 nm, the entire surface area becomes small, and the bioavailability of the peptide and the like decreases.
  • the preferred upper limit is 1000 nm, and the preferred lower limit is not particularly limited, but about 1 nm is the limit.
  • the spinning method of the carrier fiber is not particularly limited as long as it is a method capable of obtaining a carrier fiber having a fiber diameter in the above range, but it is preferable to perform spinning by electrospinning.
  • the polymer that is the raw material of the carrier fiber is dissolved in a solvent alone or simultaneously with the peptide or the like, or the polymer that is the raw material of the carrier fiber is melted.
  • a method of forming carrier fibers or fibers on the collector by filling the syringe with the resin composition obtained by the above and then injecting the resin composition while applying a voltage between the needle of the syringe and the collector, etc. Can be used.
  • the peptide and / or the pharmacologically acceptable salt or ester of the peptide is supported on the surface and / or inside of the carrier fiber.
  • the form of the support is not particularly limited, and may be bonded by physical adsorption or coexistence, or may be chemically bonded, but is preferably physically bonded. .
  • the method for physically binding (hereinafter also referred to as the above-mentioned peptide) to the carrier fiber is not particularly limited.
  • the carrier fiber is produced by electrospinning only the polymer that is the raw material of the carrier fiber.
  • the carrier fiber is produced by electrospinning, in which the peptide or the like may be physically bonded later, the peptide or the like may be physically bonded at the same time.
  • the carrier fiber includes the peptide or the like.
  • the carrier fiber includes the peptide or the like.
  • examples thereof include a method in which the solution is sprayed and dried, and a method in which a powder such as the above peptide is applied to the carrier fiber.
  • a method of physically bonding the peptide or the like at the same time specifically, for example, electrospinning to a mixed solution or a mixed melt of the peptide or the like and a polymer that is a raw material of the carrier fiber.
  • the method of producing the fiber of this invention by applying is mentioned.
  • a method for producing fibers is preferable by applying electrospinning to a mixed solution of the above-mentioned peptide and the like and a polymer that is a raw material for the carrier fibers.
  • the method of chemically bonding the peptide or the like to the carrier fiber is not particularly limited, and the fiber may be produced by electrospinning after chemically bonding! /, And by electrospinning. It may be chemically bonded after forming the carrier fiber. In this bonding, it may be indirectly covalently bonded through a spacer having a plurality of functional groups which may be directly covalently bonded to the functional group of the polymer used as the raw material of the carrier fiber.
  • the functional group include an epoxy group, an amino group, a carboxyl group, an a-chloromethyl group, and an ⁇ -chloroacetamidomethyl group.
  • the fiber of the present invention is not particularly restricted but includes loading amount such as the peptide is selected in a wide range properly, preferable lower limit is 10_ 7 wt%, the desirable upper limit is 10 wt%. If it is less than 10-7% by weight, it may not be able to exert the effect of wound healing action and the like having the peptide or the like to the charge amount, more than 10 wt%, this manufacturing problems arise and force s is there.
  • the fiber of the present invention may contain other pharmacologically active ingredients as necessary.
  • the other pharmacologically active ingredients described above are not particularly limited, and include, for example, wound healing drugs, analgesics, anti-inflammatory drugs, antihistamines, prostaglandins, antiallergic agents, corticosteroids, immunosuppressants, antibacterial agents.
  • Agent bactericidal agent, antifungal agent, antiviral agent, hemostatic agent, astringent agent, antidiabetic agent, antineoplastic agent, anthelmintic agent, antiarrhythmic agent, anticoagulant agent, antidepressant, antiepileptic agent, antihypertensive blood pressure , Antimuscarinic, antithyroid, anti-anxiety sedative, beta-adrenergic receptor blocker, cough suppressant, diuretic, dopaminergic, sex hormone, sympathomimetic, parasympathetic, vasodilator Agents and the like.
  • an appropriate additive may be added to the fiber of the present invention.
  • the additive is not particularly limited, and examples thereof include excipients, surfactants, stabilizers, fragrances, colorants, sweeteners, anticoagulants, and coagulation accelerators.
  • the use of the fiber of the present invention is not particularly limited.
  • the fiber of the present invention is used as a medicine for prevention and / or treatment of various diseases, as a material for examination / diagnosis of various diseases, or as a material for research use. Used.
  • the application site when the fiber of the present invention is used as a medicine is not particularly limited, and can be applied to various sites depending on the purpose.
  • Neural tissue ⁇ Can be applied to damaged tissue such as vascular tissue.
  • Oral, intravenous, intraarterial, subcutaneous, intradermal, intramuscular, inhalation, ophthalmic, and nasal administration can also be performed.
  • body fluids taken out of the body, such as blood and blood components, can be treated with the fibers of the present invention and returned to the body.
  • the use of the fiber of the present invention as a pharmaceutical is not particularly limited, and for example, it is used for the prevention and / or treatment of wounds, and for the generation and / or regeneration of tissues such as bone 'tooth' nerve 'blood vessels. In addition, it is used for the prevention and / or treatment of inflammatory diseases, infectious diseases and malignant neoplasms.
  • the fiber of the present invention may further have a water-resistant layer or a waterproof layer depending on the application. Furthermore, you may have a retention layer. Specifically, for example, for the purpose of applying to wound skin and the like, the carrier fiber carrying the peptide or the like is held by a mesh-like holding layer, thereby preventing falling off and the like. It may be possible to absorb the exudate from the wound and prevent external irritation by laminating a water-absorbing layer and a waterproof layer in order on one side to form a sheet. In addition, for example, for the purpose of oral administration, the carrier fiber carrying the peptide or the like is held by a holding layer, and the outer surface of the holding layer is covered with a water absorbing layer and / or a waterproof layer. Thus, it is conceivable to control the release of the peptide and the like.
  • the water-absorbing layer is a layer mainly composed of a water-absorbing polymer.
  • the water-absorbing layer is applied particularly to damaged tissues such as wound skin, bone tissue, periodontal tissue, nerve tissue, and vascular tissue.
  • liquid components such as leachate can be absorbed, and the effect of the peptide and the like can be enhanced synergistically.
  • the material of the water-absorbing layer is not particularly limited, and examples thereof include polyurethane, poly (ethylene oxide), polybutyl alcohol, polybutylpyrrolidone, carrageenan, senorelose, hydroxyethinoresenorelose, hydroxypropinoresenorelose, Hi Norelloacetate phthalate, methinoresenorelose, ethinoresenorelose, starch, hydroxychetyl starch, starch glycolate sodium, gelatin, collagen, polyacrylate resin, sodium carboxymethylcellulose, alginic acid, hyaluronic acid, chitosan, and These salts or esters are exemplified. These may be used alone or in combination of two or more. These copolymers can also be used.
  • the waterproof layer is a layer mainly composed of a hydrophobic polymer.
  • the waterproof layer is applied particularly to damaged tissues such as wound skin, bone tissue, periodontal tissue, nerve tissue, and vascular tissue. In this case, it is possible to prevent liquid components such as leachate from leaking out and contaminate the surroundings, or to prevent infection caused by invasion of microorganisms from the outside or invasion of foreign matter.
  • the material of the waterproof layer is not particularly limited, and examples thereof include polyurethane, poly (ethylene oxide), polyethylene, polypropylene, polylactic acid, polyglycololeic acid, polydioxanone, gizzard, polyamino acid, polyacetic acid butyl, polychlorinated butyl, and polyacrylonitrile.
  • the holding layer is a layer for holding the carrier fiber carrying the peptide or the like, and having the holding layer allows the interaction between the application site and the carrier fiber carrying the peptide or the like. Without hindering, it is possible to prevent the carrier fiber carrying the peptide or the like from falling off.
  • the material of the retaining layer is not particularly limited, and examples thereof include polyurethane, poly (ethylene oxide), polyvinylinoreconole, polyvinylinolepyrrolidone, carrageenan, cellulose, hydranolose, hydroxypropinoremethinoresenorelose phthalate, Senorelose acetate phthalate, methinoresenololose, ethinorescenellose, starch, hydroxyethinole starch, sodium starch glycolate, gelatin, collagen, polyethylene, polypropylene, polyethylene Poly (lactic acid), poly (dalycolic acid), polydioxanone, silk, polyamino acid, poly (vinyl acetate), poly (chlorinated), poly (acrylonitrile), polystyrene, poly (acrylic acid), poly (methyl acrylate), poly (methacrylic acid), poly (methyl methacrylate), polyvinylidene chloride, Polyvinylidene fluoride, poly
  • the method for producing the fiber of the present invention is not particularly limited.
  • the peptide represented by the formula (1) and / or a pharmacologically acceptable salt or ester of the peptide, and a carrier A method having a step of preparing a resin composition containing a polymer that is a raw material of the fiber and a step of electrospinning the resin composition can be used. Such a method for producing a fiber is also one aspect of the present invention.
  • the fiber production method of the present invention first, the peptide represented by the above formula (1) and / or the pharmacologically acceptable salt or ester of the above peptide and the raw material for the carrier fiber are used.
  • the process of preparing the resin composition containing a limer is performed. Specifically, a resin composition is prepared by adding an appropriate amount of the above-described peptide or the like and a polymer that is a raw material for the carrier fiber and a solvent, followed by stirring.
  • the solvent is not particularly limited, but esters such as ethyl acetate, alcohols such as methanol, ethanol and propanol, ethers such as ethyl ether, ketones such as acetone and methyl ethyl ketone, formic acid
  • esters such as ethyl acetate, alcohols such as methanol, ethanol and propanol
  • ethers such as ethyl ether
  • ketones such as acetone and methyl ethyl ketone
  • carboxylic acids such as acetic acid and trifluoroacetic acid, dichloromethane, chloroform, tetrahydrofuran, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, divalent xylene, 1-methyl-2-pyrrolidone, hexafluoroisopropanol, water or these And the like.
  • the electrospinning a force capable of using a conventionally known method. Specifically, for example, after filling a syringe with the resin composition, a resin composition is applied while applying a voltage between a needle and a collector of the syringe. A method of injecting an object can be used.
  • the electrospinning conditions are not particularly limited, but the preferable lower limit of the applied voltage is 5 kV, preferably! /, And the upper limit is 40 kV.
  • a force that can produce a fiber having a predetermined fiber diameter can be manufactured by adjusting the applied voltage, the injection speed, the needle thickness, and the like.
  • the fiber diameter of the obtained fiber may differ.
  • the applied voltage, the injection speed, the needle thickness, etc. are adjusted each time according to conditions such as the type of injection machine used, the type of electrospinning apparatus, and the weather during the manufacturing. By adjusting, a fiber having a desired fiber diameter can be produced.
  • the present invention relates to an excellent wound healing promoting action with high drug release and / or bioavailability, allergic and non-allergic inflammation inhibiting action, immunosuppressing action, antibacterial action, antitumor action, site A fiber having a force-in inducing action and the like and a method for producing the fiber can be provided.
  • Actinomycetes S. nobilis obtained from RIKEN, 5 pieces of 500 mL Sakaguchi Slasco containing 50 mL of starch-ammonium medium supplemented with 0.2% (w / v) yeast extract, 26 ° C, 150 rpm, 120 Time-shaking culture (pre-culture) was performed. Subsequently, 240 mL of the pre-cultured bacterial solution was inoculated into a 20 L-volume fermentor containing 12 L of the same medium, and cultured for 24 hours (pre-culture) at 26 ° C., 410 rpm, and aeration rate of 4 L / min.
  • starch 'ammoudium medium (lg soluble soluble lg in distilled water lOOmL, 0 ⁇ 05g dipotassium hydrogen phosphate, 0 ⁇ 05g ammonium chloride) 14L pre-cultured in 200L jar fermenter containing OL 12 L of the solution was inoculated and seeded at 26 ° C for 24 hours.
  • electrospinning is performed using an electrospinning unit (made by Kato Tech Co., Ltd.) under the conditions of a voltage of 15 kV, a spinning distance of 10 cm, a target speed of 6 m / min, a traverse speed of 20 cm / min, and a syringe speed of 0.075 mm / min.
  • a fiber having a peptide content of 1% by weight was prepared.
  • the obtained fiber was observed with a scanning electron microscope and the average diameter of the fiber was measured by image analysis, it was about 20 Onm.
  • the obtained fibers were observed with a scanning electron microscope, and the average diameter of the fibers was measured by image analysis.
  • the peptide content of the obtained fiber (table; as shown here, 1, 0.5, 0.25, 0.1, 0.05, or 0.025 weight) %Met.
  • Example 1 The peptides obtained in Example 1 0.1 wt%, the polylactic acid (manufactured by Mitsui Chemicals, Inc., trade name Ganoderma ⁇ H- 100) to 10 weight 0/0 containing 1, 1, 1, 3, 3, 3 A fiber having a peptide content of 1% by weight was prepared by preparing —hexafluoro-2-propanol solution and electrospinning according to Example 1.
  • the obtained fiber was observed with a scanning electron microscope, and the average diameter of the fiber was measured by image analysis and found to be about 200 nm.
  • polyurethane fibers having a peptide content of 1% by weight, each having an average fiber diameter of about 1, about 1000 or about 2000 nm as shown in Table 3, were prepared.
  • polylactic acid fibers having an average fiber diameter of about 1, about 1000 or about 2000 nm as shown in Table 3 and a peptide content of 1% by weight were prepared.
  • Example 2 0.1% by weight of peptides obtained in Example 1, poly epsilon - Power Purorataton (molecular weight 8 0, 000, Wako Pure Chemical Industries, Ltd.) 10 wt 0/0 containing to dichloromethane over dimethylformamide (8: 2 )
  • a solution having a peptide content of 1% by weight was prepared by electrospinning according to Example 1 except that a solution was prepared and an electrospinning apparatus (manufactured by Imoto Seisakusho, 1MC-164E type) was used.
  • the obtained fiber was observed with a scanning electron microscope, and the average diameter of the fiber was measured by image analysis and found to be about 200 nm.
  • 10 wt 0/0 containing 1, 1, 3, 3, 3- Hexafluor mouth—2-propanol solution was prepared and electrospun according to Example 1 except that an electrospinning apparatus (type 1MC-164E manufactured by Imoto Seisakusho Co., Ltd.) was used. Fibers were made. The obtained fiber was observed with a scanning electron microscope,
  • the obtained fiber was observed with a scanning electron microscope, and the average diameter of the fiber was measured by image analysis and found to be about 200 nm.
  • Example 1 The peptide obtained in Example 1 was mixed with a dimethylacetamide solution containing 0.1% by weight, chitin (manufactured by Sigma, powder) containing 10% by weight of 8% by weight of lithium chloride, and kneaded with a kneader. A solution was made and filtered. This solution was defoamed and filtered to become a clear solution with high viscosity. A fiber having a peptide content of 1% by weight was produced by electrospinning according to Example 1.
  • the obtained fiber was observed with a scanning electron microscope, and the average diameter of the fiber was measured by image analysis and found to be about 200 nm.
  • An aqueous solution containing 4% by weight of sodium alginate (Sigma, Medium viscosity grade) and an aqueous solution containing 4% by weight of polyethylene oxide (Sigma, average molecular weight 900,000 Da) were mixed at a ratio of 80:20.
  • An aqueous solution containing 0.5% by weight of 13 ⁇ 4 01- and 5% by weight of dimethyl sulfoxide was prepared, and the peptide obtained in Example 1 was contained by 0.04% by weight.
  • a fiber having a peptide content of 1% by weight was produced by electrospinning according to Example 1.
  • the obtained fiber was observed with a scanning electron microscope, and the average diameter of the fiber was measured by image analysis and found to be about 200 nm.
  • Example 1 Similar to Examples 1, 2 and 8, except that the peptide obtained in Example 1 was not used.
  • the fiber was produced by performing the method of. Each fiber has an average diameter of about 200 ⁇ m.
  • Example 2 By suspending the peptide 1 or 0.1% by weight obtained in Example 1 in a 0.5% by weight aqueous solution of carboxymethyl cellulose sodium (CMC-Na), the peptide content is 1 or 0.1%. A weight percent CMC-Na suspension was prepared.
  • CMC-Na carboxymethyl cellulose sodium
  • Example 2 Dissolve the peptide obtained in Example 1 in methanol to 8 mg / mL or 0.4 mg / mL. Use 10 ml of the peptide to form gauze (20 cm X 20 cm, 8. Og, fiber diameter: 200). Gauze with a peptide content of 1 or 0.05% by weight was prepared by spraying uniformly and drying.
  • Comparative Example 10 was obtained by uniformly spraying 10 mL of methanol on gauze (20 cm ⁇ 20 cm, 8. Og, fiber diameter: 200 m) without using the peptide obtained in Example 1, and drying it.
  • Example 2 By fully kneading the peptide 1 or 0.1% by weight obtained in Example 1 with an oily ointment base (Plastibase, manufactured by Taisho Pharmaceutical Co., Ltd.) in a mortar, the peptide content is 1 or 0.1% by weight. Oily ointment was obtained.
  • Example 13 The oily ointment consisting only of the oily ointment base containing no peptide obtained in Example 1 was designated as Comparative Example 13.
  • polyacryl nitrile fibers having an average fiber diameter of about 5000 nm and a peptide content of 1% by weight were produced by electrospinning.
  • Example 8 a polylactic acid fiber having an average fiber diameter of about 5000 nm and a peptide content of 1% by weight was produced by electrospinning.
  • Example 15 a poly ⁇ -force prolataton fiber having an average fiber diameter of about 5000 nm and a peptide content of 1% by weight was produced by electrospinning.
  • gelatin fibers having an average fiber diameter of about 5000 nm and a peptide content of 1% by weight were produced by electrospinning.
  • chitosan fibers having an average fiber diameter of about 5000 nm and a peptide content of 1% by weight were produced by electrospinning.
  • chitin fibers having an average fiber diameter of about 5000 nm and a peptide content of 1% by weight were produced by electrospinning.
  • Example 19 an alginate / polyethylene oxide co-spun fiber having an average fiber diameter of about 5000 nm and a peptide content of 1% by weight was produced by electrospinning.
  • the back of 7-week-old male Wistar rats was shaved and the test substance was administered subcutaneously to the back.
  • the dose was set so that the obtained peptide would be the amount shown in Table 1 or Table 2, and the control group containing no peptide had the same weight as that and was administered subcutaneously.
  • Seven days after administration of the test substance the formed granulation tissue was taken out and weighed to determine the granulation ability. Evaluated.
  • the control group (Comparative Examples;! To 3) has a remarkable wound area in the group administered with the fibers of the present invention (Examples 1, 2, and 8). Shrinkage was observed, and the effect was 0.5% by weight of the obtained peptide, Na suspension (Comparative Examples 4-5), peptide-containing gauze (Comparative Examples 7-8) and peptide-containing ointment (Comparative There is a significant difference from Examples 10 to 11).
  • the number of days required for wound healing in the group administered with the fibers of the present invention (Examples 1, 2, and 8) relative to the control group (Comparative Examples 1 to 3).
  • the fiber of the present invention has increased bioavailability at the time of administration.
  • test substance was weighed in Nettuel (Cowung Co., mesh size 500 m) and set in a 12-well plate. The amount of the test substance was set so that the obtained peptides had the amounts shown in Table 1 and Table 2, respectively.
  • As a test solution add 2 mL of 2% hydroxypropyl ⁇ -cyclodextrin (Rocket) aqueous solution to a 12-well plate, leave at 37 ° C, collect the test solution over time, and release the peptide. was quantified by high performance liquid chromatography. This test was conducted for 3 cases each, and the average value of the release rate was calculated. The results are shown in Tables;!
  • the fiber of the present invention has enhanced drug release.

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Abstract

La présente invention concerne une fibre présentant d'excellentes propriété de libération de médicament et/ou de biodisponibilité d'un médicament, et qui se révèle également excellente dans les activités d'accélération de cicatrisation, de prévention d'une inflammation allergique ou non allergique, d'immunosuppression, ainsi que les activités antibactérienne, anti-tumorale, d'induction de cytokines et analogue. La présente invention concerne également un procédé de production de ladite fibre. L'invention concerne plus particulièrement une fibre comprenant une fibre de transport présentant un diamètre inférieur ou égal à 2 000 nm et un peptide représenté par la formule (1) ou un sel pharmacologiquement acceptable ou un ester de celui-ci porté sur la surface et/ou l'intérieur de la fibre de transport.
PCT/JP2007/066556 2006-08-25 2007-08-27 Fibre et procédé de production de fibre Ceased WO2008023818A1 (fr)

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JP2006229139 2006-08-25
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012052264A (ja) * 2010-09-01 2012-03-15 Teijin Ltd 細胞特異的ペプチドを含有する繊維構造体
WO2014042250A1 (fr) * 2012-09-13 2014-03-20 テイカ製薬株式会社 Fibre ultrafine contenant un médicament et son utilisation
CN112353996A (zh) * 2020-11-24 2021-02-12 江西美宝利医用敷料有限公司 一种可溶性止血纱布的制作方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11178911A (ja) * 1997-10-14 1999-07-06 Sekisui Chem Co Ltd 医療材料
JP2005534716A (ja) * 2002-08-07 2005-11-17 スミスクライン・ビーチャム・コーポレイション 電気紡糸した非晶質医薬組成物
JP2006501373A (ja) * 2002-04-04 2006-01-12 ザ　ユニバーシティ　オブ　アクロン 不織繊維集成体

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11178911A (ja) * 1997-10-14 1999-07-06 Sekisui Chem Co Ltd 医療材料
JP2006501373A (ja) * 2002-04-04 2006-01-12 ザ　ユニバーシティ　オブ　アクロン 不織繊維集成体
JP2005534716A (ja) * 2002-08-07 2005-11-17 スミスクライン・ビーチャム・コーポレイション 電気紡糸した非晶質医薬組成物

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012052264A (ja) * 2010-09-01 2012-03-15 Teijin Ltd 細胞特異的ペプチドを含有する繊維構造体
WO2014042250A1 (fr) * 2012-09-13 2014-03-20 テイカ製薬株式会社 Fibre ultrafine contenant un médicament et son utilisation
JP2014055119A (ja) * 2012-09-13 2014-03-27 Teika Seiyaku Kk 薬物含有超極細ファイバーおよびその利用
CN112353996A (zh) * 2020-11-24 2021-02-12 江西美宝利医用敷料有限公司 一种可溶性止血纱布的制作方法

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