WO1996041643A1 - Procede de traitement et agent antiviraux - Google Patents

Procede de traitement et agent antiviraux Download PDF

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Publication number
WO1996041643A1
WO1996041643A1 PCT/JP1996/001587 JP9601587W WO9641643A1 WO 1996041643 A1 WO1996041643 A1 WO 1996041643A1 JP 9601587 W JP9601587 W JP 9601587W WO 9641643 A1 WO9641643 A1 WO 9641643A1
Authority
WO
WIPO (PCT)
Prior art keywords
zinc
hepatitis
interferon
carboxypyridin
group
Prior art date
Application number
PCT/JP1996/001587
Other languages
English (en)
Japanese (ja)
Inventor
Masatomo Mori
Takeaki Nagamine
Makoto Kuboki
Original Assignee
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 Otsuka Pharmaceutical Co., Ltd. filed Critical Otsuka Pharmaceutical Co., Ltd.
Priority to AU60150/96A priority Critical patent/AU6015096A/en
Publication of WO1996041643A1 publication Critical patent/WO1996041643A1/fr

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Classifications

    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P31/12—Antivirals

Definitions

  • the present invention relates to an antiviral method and an antiviral agent, particularly to a method for treating hepatitis and a therapeutic agent for hepatitis.
  • Hepatitis C is said to be a chronic problem because it is easy to become chronic and has a high probability of progressing to cirrhosis and liver cancer.
  • interferon has a therapeutic effect on the above-mentioned hepatitis because it has an effect such as an antiviral effect.
  • the effective treatment rate is still unsatisfactory, and the effective treatment rate is particularly low depending on the type of virus and the virus genotype.
  • Ri its effective therapeutic index of about 3 5% Hododea in hepatitis C, especially c I pulse amount, i.e. effective treatment rate HCVRNA weight relative to 1 0 6 copies / ml by Ri higher hepatitis C was only about 10 to 20%.
  • hepatitis C (1, II, III, IV and V)
  • the effective treatment rates for type I and ⁇ are low.
  • WO091212288 discloses biologically active substances such as interferon and colloidal metal.
  • compositions consisting of (colloidal metal) are effective in treating cancer and immune diseases.
  • colloidal metal is used in combination to reduce the toxicity of a biologically active substance, and it is not effective for cancer and immunological diseases. It is a biologically active substance such as interferon. Therefore, WO 09/21288 also only teaches that biologically active substances such as interferon are effective in treating cancer and immune diseases. It is something.
  • the present inventor has conducted intensive studies to develop an excellent antiviral method or a therapeutic method for hepatitis, and as a result, selected from the group consisting of zinc phosphate and zinc complexes. By using at least one of them together, it is possible to synergistically increase the effective treatment rate of single administration of interferonil, and to achieve excellent therapeutic effects.
  • the above-mentioned method is considered to be effective in the treatment of transgene-type hepatitis with a low effective treatment rate in the case of interferon administration alone, especially hepatitis C and II.
  • the present invention provides an antiviral method, particularly a method for treating hepatitis and an antiviral method, comprising using interferon in combination with at least one selected from the group consisting of zinc salts and zinc complexes.
  • the present invention relates to an antiviral agent comprising a combination of turf mouth and at least one selected from the group consisting of a zinc salt and a zinc complex, particularly a therapeutic agent for hepatitis.
  • the antiviral agent of the present invention exhibits a remarkable therapeutic effect on any of A, B and C hepatitis.
  • the agent of the present invention is also excellent for hepatitis C, a genotype of virus having a low effective treatment rate, and hepatitis C, which has a high viral load, when administration of interferon alone is ineffective. It can exhibit therapeutic effects and is particularly effective against hepatitis B and C.
  • the agent of the present invention is also effective against zinc deficiency such as skin diseases frequently associated with hepatitis patients, abnormal taste, alopecia, fever, eye pain, menstrual abnormalities, mental symptoms such as ⁇ .
  • the antiviral agent of the present invention has excellent effects on various viral infectious diseases based on its antiviral action. I can do it.
  • the interface used in the present invention is not particularly limited, and conventionally well-known ones can be widely used.
  • an interface X such as a natural type or a recombinant type can be used. Examples include Interferon S, Interferon 7, and the like.
  • zinc salt and the zinc complex conventionally known ones can be widely used without any particular limitation.
  • the antiviral agent (therapeutic agent for hepatitis) of the present invention is usually used in the form of a general pharmaceutical preparation.
  • the formulations are prepared with diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and lubricants which are commonly used.
  • diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and lubricants which are commonly used.
  • Various forms of this pharmaceutical preparation can be selected according to the purpose of treatment, and typical examples are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories. Preparations, injections (solutions, suspensions, etc.), ointments, inhalants, sprays and the like.
  • carriers such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, and caic acid Excipients, water, ethanol, propanol, single-mouthed tablets, glucose solutions, starch solutions, gelatin solutions, carboxymethyl cellulose, ceramics, methylcellulose, phosphoric acid Binders such as sodium, polyvinylpyrrolidone, dried starch, sodium alginate, powdered starch, laminating ⁇
  • Disintegrators such as naran powder, sodium hydrogencarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, monoglyceride stearate, starch, and lactose , Sucrose, stearin, cocoa butter, disintegration inhibitor such as hydrogenated oil, quaternary ammonium base, absorption promoter such as sodium lauryl sulfate, humectant such as glycerin and starch, Adsorbents such as starch, lactose, kaolin, bentonite, colloidal gay acid, lubricants such as purified talc, stearate, powdered boric acid, polyethylene glycol, etc. can be used. .
  • the tablet can be made into a tablet coated with a usual coating, if necessary, for example, a sugar-coated tablet, a gelatin-coated tablet, an enteric-coated tablet, a film-coated tablet, a double tablet, or a multilayer tablet.
  • the carrier may be, for example, excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oils, kaolin, talc, etc. Binders such as gelatin, ethanol and the like. Disintegrators such as laminaran and kanthe can be used.
  • the carrier for example, polyethylene glycol, cocoa butter, higher alcohol, higher alcohol esters, gelatin, semi-synthetic glyceride and the like can be used.
  • Preparation of capsules is carried out according to a conventional method, usually with various carriers exemplified above and the active ingredient compound of the present invention. Is mixed and filled into a hard gelatin capsule, a hard capsule, or the like.
  • solutions, emulsions and suspensions are preferably sterile and isotonic with blood.
  • water for molding into these forms, for example, water, lactic acid aqueous solution, ethyl alcohol, propylene glycol, ethoxylated isostear linoleal alcohol, and polyoxyethylene sorbitan fatty acid esters can be used as diluents. .
  • a sufficient amount of salt, glucose, or glycerin to prepare an isotonic solution may be contained in the pharmaceutical preparation.
  • Desiccants, soothing agents and the like may be added.
  • a coloring agent, a preservative, a flavor, a flavoring agent, a sweetening agent, and other pharmaceuticals may be contained in the pharmaceutical preparation.
  • diluents such as white petrolatum, red and white may be used.
  • Raffin, glycerin, cellulose derivatives, polyethylene glycol, silicone, bentonite and the like can be used.
  • interferon and at least one selected from the group consisting of zinc salts and zinc complexes may be simultaneously contained in the pharmaceutical preparation, or may be contained in separate pharmaceutical preparations.
  • the interferon and at least one selected from the group consisting of zinc salts and zinc complexes, These pharmaceutical preparations may be used in combination for treatment of inflammation and the like.
  • the freeze-dried agent of interferon and the desiccant of zinc salt and / or zinc complex can be combined and dissolved in distilled water for injection before use.
  • the amount of at least one selected from the group consisting of interferon, zinc salt and zinc complex to be contained in the pharmaceutical preparation of the present invention is not particularly limited as long as it is an effective amount, and is in a wide range. Is selected as appropriate.
  • the method of administration of the pharmaceutical preparation of the present invention is not particularly limited, and is variously determined according to the age, gender and other conditions of the patient, disease state, etc., and various preparation forms. It is administered orally or parenterally. For example, it is orally administered in the form of tablets, pills, solutions, suspensions, emulsions, granules, and capsules, and is injected, and if necessary, mixed with ordinary rehydration solutions to give intravenous, intramuscular, or intradermal In addition to being administered internally, subcutaneously or intraperitoneally, it is administered rectally as a suppository, orally or nasally as a spray or inhalant, or as an ointment.
  • the dose of the pharmaceutical preparation of the present invention to a human is appropriately selected depending on the age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but interferon is usually about 100 per day. 10,000 to 300,000 IUZ body, preferably about 200,000 to ⁇
  • IUZ body administered within the range of IUZ body, selected from the group consisting of zinc salts and zinc complexes At least one is usually about 5 to 800 mg body per day, preferably about 5 to 800 mg body per day.
  • the preparation may be administered once to several times a day.
  • a dosage smaller than the above-mentioned dosage range may be sufficient, or may be necessary beyond the range.
  • HCVRNA amount 1 0 6 copies / ml in patients with hepatitis C is on the more than Lee Ntafu L Russia down ⁇ 1 0 0 0 million IU the two weeks after intramuscular injection Rento, Ri by 3 weeks They were administered three times a week every other day.
  • Patients A hepatitis C ⁇ type I, HCV RNA 2 ⁇ 10 6 copies / ml
  • Patient B hepatitis C type III, HCV RNA
  • Table 1 shows the amount of virus at 6 months after the final administration of interferon ⁇ and polaprezinc was measured by competitive quantification and qualitative test of amplicor, and the results are also shown.
  • the blanks in Table 1 have not been measured. The same applies to Tables 2 and 3 below.
  • hepatitis C (C hepatitis type II, HCV RNA quantity 1 X 1 0 7 copies / ml )
  • the patient b (C hepatitis type II of hepatitis C, HCV RNA quantity 1 X 1 0 7 copies / ml ) and hepatitis C Te patients (C hepatitis type II, with respect to HCVRNA amount 3 X 1 0 5 copies / ml )
  • the patient a will, HCVRNA amount to less than 1 X 1 0 2 copies / nil after 8 days
  • the patient b is, HCVRNA amount after 2 9 days 1 x 1 0 2 copies / ml below
  • the patient c can indicate whether a HCVRNA amount drops respectively below 4 X 1 0 2 copies / ml was found after 8 days.
  • Hepatitis C patients I C hepatitis type II, HCV RNA quantity 1 X 1 0 7 copies / ml
  • the patient port of hepatitis C C hepatitis type II, HCV RNA amount 5 x 1 0 3 copies / ml
  • patients with hepatitis C hepatitis C type II, HCV RNA level of 5 ⁇ 10 6 copies / ml
  • the interferon ⁇ was 10%.
  • administration was performed every other day three times a week from the third week. From the start of interferon ⁇ administration, the amount of virus was measured by competitive quantification and qualitative test of amplicora, using 300 mg of zinc sulfate orally once a day.
  • Oreate 0 4 g Sodium metabisulfite 0 1 g Methylenorenolaben 0 18 g Propinolayer * Laben 0 0.2 g Distilled water for injection 0 0 m1 Above The parabens, sodium metabisulfite and sodium chloride are dissolved in about half the above amount of distilled water with stirring at 80.
  • the resulting solution was cooled to 4 0 ° C, the active ingredient compound of the present onset bright, then the port re ethylene Renguri call ⁇ beauty Po Li oxyethylene Renso Honoré bicycloalkyl evening Nmono Oree Bok, tertiary dissolving above SL solution Then, add distilled water for injection to the solution to make the final volume, and sterilize by sterile filtration using an appropriate phenol paper to prepare an injection.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Zoology (AREA)
  • Virology (AREA)
  • Oncology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Cet agent antiviral et un remède contre l'hépatite procurent un excellent effet thérapeutique même contre le virus de génotype C ou l'hépatite C à forte charge virale alors que l'administration d'interféron seul ne procure qu'un faible taux de guérison. Ce remède comprend de l'interféron et au moins un composant sélectionné dans le groupe consistant en des sels et des complexes de zinc.
PCT/JP1996/001587 1995-06-12 1996-06-12 Procede de traitement et agent antiviraux WO1996041643A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU60150/96A AU6015096A (en) 1995-06-12 1996-06-12 Antiviral method and antiviral agent

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP7/144866 1995-06-12
JP14486695 1995-06-12
JP7/314997 1995-12-04
JP31499795 1995-12-04
JP05178496A JP3837769B2 (ja) 1995-06-12 1996-03-08 抗ウイルス剤
JP8/51784 1996-03-08

Publications (1)

Publication Number Publication Date
WO1996041643A1 true WO1996041643A1 (fr) 1996-12-27

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ID=27294440

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1996/001587 WO1996041643A1 (fr) 1995-06-12 1996-06-12 Procede de traitement et agent antiviraux

Country Status (3)

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JP (1) JP3837769B2 (fr)
AU (1) AU6015096A (fr)
WO (1) WO1996041643A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7968122B2 (en) 2003-12-10 2011-06-28 Adventrx Pharmaceuticals, Inc. Anti-viral pharmaceutical compositions
WO2022005848A1 (fr) * 2020-07-01 2022-01-06 Nelson Deanna J Combinaisons de carnosine et de zinc pour le traitement et la prévention d'infections virales

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1023901A4 (fr) * 1997-10-13 2004-10-27 Otsuka Pharma Co Ltd Produit d'amelioration de l'effet curatif sur l'hepatite c et son application
DE19818842C1 (de) * 1998-04-28 2000-01-05 Suedzucker Ag Erkältungsmittel
JPWO2006033453A1 (ja) * 2004-09-22 2008-05-15 学校法人順天堂 インターフェロン作用物質の活性増強剤
JP2008195690A (ja) * 2007-02-15 2008-08-28 Gunma Univ インターフェロンα／β受容体誘導剤
JP7028401B2 (ja) 2018-02-23 2022-03-02 日清紡ケミカル株式会社 水性カルボジイミド含有液の製造方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03500286A (ja) * 1987-02-24 1991-01-24 シェリング・コーポレーション 安定なインターフェロン複合体
JPH05194538A (ja) * 1992-01-14 1993-08-03 Res Inst For Prod Dev ２−アミノエタンスルホン酸亜鉛錯体
JPH05194345A (ja) * 1992-01-14 1993-08-03 Res Inst For Prod Dev Ｎ−（３−アルキル（またはアルケニル）−４−ヒドロキシベンゾイル）グリシン亜鉛錯体
JPH0649077A (ja) * 1992-06-18 1994-02-22 Res Inst For Prod Dev ２−アミノエタンスルホン酸亜鉛錯化合物
JPH06510998A (ja) * 1991-09-13 1994-12-08 サイクローン・ファーマシューティカルズ・インコーポレイテッド Ｃ型肝炎を治療する組成物および方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03500286A (ja) * 1987-02-24 1991-01-24 シェリング・コーポレーション 安定なインターフェロン複合体
JPH06510998A (ja) * 1991-09-13 1994-12-08 サイクローン・ファーマシューティカルズ・インコーポレイテッド Ｃ型肝炎を治療する組成物および方法
JPH05194538A (ja) * 1992-01-14 1993-08-03 Res Inst For Prod Dev ２−アミノエタンスルホン酸亜鉛錯体
JPH05194345A (ja) * 1992-01-14 1993-08-03 Res Inst For Prod Dev Ｎ−（３−アルキル（またはアルケニル）−４−ヒドロキシベンゾイル）グリシン亜鉛錯体
JPH0649077A (ja) * 1992-06-18 1994-02-22 Res Inst For Prod Dev ２−アミノエタンスルホン酸亜鉛錯化合物

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7968122B2 (en) 2003-12-10 2011-06-28 Adventrx Pharmaceuticals, Inc. Anti-viral pharmaceutical compositions
US8470346B2 (en) 2003-12-10 2013-06-25 Mast Therapeutics, Inc. Anti-viral pharmaceutical compositions
WO2022005848A1 (fr) * 2020-07-01 2022-01-06 Nelson Deanna J Combinaisons de carnosine et de zinc pour le traitement et la prévention d'infections virales

Also Published As

Publication number Publication date
JP3837769B2 (ja) 2006-10-25
JPH09216831A (ja) 1997-08-19
AU6015096A (en) 1997-01-09

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