WO2002067920A1 - Remedes pour hepatite c chronique - Google Patents

Remedes pour hepatite c chronique Download PDF

Info

Publication number
WO2002067920A1
WO2002067920A1 PCT/JP2001/007533 JP0107533W WO02067920A1 WO 2002067920 A1 WO2002067920 A1 WO 2002067920A1 JP 0107533 W JP0107533 W JP 0107533W WO 02067920 A1 WO02067920 A1 WO 02067920A1
Authority
WO
WIPO (PCT)
Prior art keywords
chronic hepatitis
hcv
administration
bezafibrate
represented
Prior art date
Application number
PCT/JP2001/007533
Other languages
English (en)
Japanese (ja)
Inventor
Takeshi Kurihara
Original Assignee
Kissei 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 Kissei Pharmaceutical Co., Ltd. filed Critical Kissei Pharmaceutical Co., Ltd.
Publication of WO2002067920A1 publication Critical patent/WO2002067920A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16B—DEVICES FOR FASTENING OR SECURING CONSTRUCTIONAL ELEMENTS OR MACHINE PARTS TOGETHER, e.g. NAILS, BOLTS, CIRCLIPS, CLAMPS, CLIPS OR WEDGES; JOINTS OR JOINTING
    • F16B39/00—Locking of screws, bolts or nuts
    • F16B39/02—Locking of screws, bolts or nuts in which the locking takes place after screwing down
    • F16B39/12—Locking of screws, bolts or nuts in which the locking takes place after screwing down by means of locknuts
    • F16B39/16—Locking of screws, bolts or nuts in which the locking takes place after screwing down by means of locknuts in which the screw-thread of the locknut differs from that of the nut
    • F16B39/18—Locking of screws, bolts or nuts in which the locking takes place after screwing down by means of locknuts in which the screw-thread of the locknut differs from that of the nut in which the locknut grips with screw-thread in the nuts as well as on the bolt
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16B—DEVICES FOR FASTENING OR SECURING CONSTRUCTIONAL ELEMENTS OR MACHINE PARTS TOGETHER, e.g. NAILS, BOLTS, CIRCLIPS, CLAMPS, CLIPS OR WEDGES; JOINTS OR JOINTING
    • F16B39/00—Locking of screws, bolts or nuts
    • F16B39/22—Locking of screws, bolts or nuts in which the locking takes place during screwing down or tightening
    • F16B39/24—Locking of screws, bolts or nuts in which the locking takes place during screwing down or tightening by means of washers, spring washers, or resilient plates that lock against the object

Definitions

  • the present invention relates to a therapeutic agent for chronic hepatitis C
  • the present invention provides a formula A- [4- (4-chlorobenzoylaminoethyl) phenoxy] isobutyric acid (generic name bezafibrate, bezafibrate, hereafter referred to as bezafibrate) or a pharmacologically acceptable salt thereof is effective
  • the present invention relates to a therapeutic agent for chronic hepatitis C contained as an ingredient.
  • Hepatitis C is a disease caused by infection of the hepatitis C virus (HCV, hereinafter referred to as HCV) from the blood. More than half of the disease becomes chronic. Therefore, drug therapy is indispensable in the treatment of chronic hepatitis C to prevent hepatocarcinogenesis.
  • HCV hepatitis C virus
  • the treatment goals for chronic hepatitis C are to maintain normal liver function, i.e., to improve liver function, and to prevent HCV-RNA continuous negativity, i.e., to remove HCV.
  • Huen has liver function-improving effects and anti-HCV effects, and although it is the most widely used, daily and total doses are prescribed, and precautions must be taken in prescribing. Its effectiveness is limited and many patients are not effective.
  • As other therapeutic agents strong minophagen C, dalitinoleritin, ursodeoxycholic acid, etc. are used, but all have only liver function improving effect, and do not affect HCV-RNA continuous negative, liver function Is used only for the purpose of sustained normality, and invalid cases are often reported.
  • Ursodeoxycholic acid has also been reported to be effective to some extent, but it has been reported that it is not recommended, and a reliable effect cannot be expected.
  • oral antiviral agents such as ofloxacin (of 1 oX acin) and levofloxacin are being studied for the purpose of removing HCV, but oral antiviral agents generally have problems with toxicity and side effects due to long-term continuous administration. In most cases, long-term continuous administration is difficult.
  • the bezafiprate of the present invention represented by the above formula (I) or a pharmacologically acceptable salt thereof has a cholesterol-lowering effect, is a compound useful as a therapeutic agent for hyperlipidemia, It is widely used in the treatment of blood disorders.
  • bezafibrate is effective in treating chronic hepatitis C.
  • the present inventor has a remarkable liver function improving effect and anti-HCV effect, is effective even in cases of interferon ineffective as a first-line drug for treating chronic hepatitis C, and has no problem of side effects even in long-term continuous administration
  • the above-mentioned formula of the present invention which has a cholesterol-lowering effect and is already widely used as a therapeutic agent for hyperlipidemia
  • the present inventors have found that the bezafibrate represented by (I) reduces hepatobiliary enzymes by long-term oral administration, suppresses HCV proliferation, and has a therapeutic effect on chronic hepatitis C in interferon-ineffective patients. Was reached.
  • the present invention also relates to a therapeutic agent for chronic hepatitis C containing as an active ingredient bezafibrate represented by the formula (I) or a pharmaceutically acceptable salt thereof. It is.
  • the present invention also relates to a method for treating chronic hepatitis C, which comprises administering an effective amount of bezafibrate represented by the formula (I) or a pharmaceutically acceptable salt thereof.
  • the present invention relates to the use of bezafibrate represented by the above formula (I) or a pharmaceutically acceptable salt thereof for producing a preparation for treating chronic hepatitis C.
  • the key points in the treatment of chronic hepatitis C are improvement of liver function, ie, reduction of hepatobiliary enzymes, and continuous elimination of HCV-RNA, ie, removal of HCV, as described above.
  • the present inventor has proposed that bezafiprate 200 be used for ineffective cases in which no improvement was observed even if interferon therapy using natural interferon ⁇ , natural interferon) 3 or recombinant interferon ⁇ -2b was continued for 6 months.
  • ALT and y-GTP hepatobiliary enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ⁇ - Changes in dartameal transferase ( ⁇ -GTP, hereafter referred to as ⁇ -GTP) were measured over time.
  • AST aspartate aminotransferase
  • ALT alanine aminotransferase
  • ⁇ -GTP dartameal transferase
  • bezafiprate also had an inhibitory effect on HCV proliferation.
  • the bezafibrate of the present invention represented by the above formula (I) has been confirmed to have a blood cholesterol lowering effect as described above, and has already been widely used as a therapeutic agent for hyperlipidemia.
  • bezafibrate has never been reported to exhibit a hepatobiliary enzyme lowering effect and an inhibitory effect on HCV proliferation due to chronic hepatitis C.
  • bezafibrate has a hepatobiliary enzyme-lowering effect and inhibits HCV proliferation. It has a remarkable therapeutic effect on chronic hepatitis C and is effective even in cases of ineffectiveness of interferve, which is the first-line drug for the treatment of chronic hepatitis C. have.
  • the bezafibrate represented by the formula (I) or a pharmacologically acceptable salt thereof of the present invention is a very useful compound as a therapeutic agent for chronic hepatitis C, and therefore, bezafiprate or a pharmacologically acceptable salt thereof.
  • a highly useful pharmaceutical composition as a therapeutic agent for chronic hepatitis C can be produced by incorporating a salt of the present invention as an active ingredient and mixing it with a pharmaceutical additive according to a conventional method as appropriate.
  • oral administration agents include powders, granules, tablets, capsules, Parenteral preparations such as dry syrups include injections, suppositories, patches and the like.
  • compositions can be mixed with appropriate pharmaceutical additives, such as shellfish, disintegrants, binders, lubricants, etc., according to the dosage form, according to the usual pharmacological techniques, and according to the usual method. It can be manufactured by dispensing.
  • appropriate pharmaceutical additives such as shellfish, disintegrants, binders, lubricants, etc.
  • powders are prepared by adding appropriate excipients, lubricants, and the like to the active ingredient, if necessary, and thoroughly mixing to obtain a powder.
  • Tablets are prepared by adding appropriate excipients, disintegrants, binders, lubricants and the like, if necessary, to the active ingredient and compressing the tablets according to the usual method. If necessary, the composition is coated as appropriate to obtain film-coated tablets, sugar-coated tablets, enteric-coated tablets and the like.
  • Capsules may be added to the active ingredient, if necessary, by adding appropriate excipients, lubricants, etc., and mixed well, or alternatively, formed into granules or fine granules by a conventional method, and filled in suitable capsules. Into capsules.
  • an immediate release or sustained release preparation can be prepared depending on the treatment method.
  • the dose of the active ingredient is appropriately determined according to the patient's age, body weight, degree of disease, therapeutic effect, and the like.
  • a pharmacologically acceptable salt thereof is administered in an amount of 100 to 100 Omg, preferably 400 to 60 Omg per day for an adult. It may be increased or decreased as appropriate according to the symptoms.
  • the content of the present invention will be described in more detail by the following examples.
  • Hepatitis C was diagnosed by liver biopsy, and interferon therapy with natural interferon o; natural interferon j3 or transgenic interferon ⁇ - 2b was ineffective for 6 months.
  • the effect of bezafibrate on the treatment of chronic hepatitis C was confirmed in patients who underwent chronic hepatitis C.
  • the target cases, administration method, measurement items and results are as follows.
  • AST, ALT, y-GTP and HCV-RNA were quantified before administration of bezafibrate, and at 1, 3, and 6 months after administration, and compared with the values before administration.
  • HCV-RNA quantification was performed using a copass amplifier monitor (Co bas A m 1 icor Monitor) method. Quantitative values are expressed as IU / L for AST, AL ⁇ , ⁇ -GT ⁇ , and KIU / mL for HCV-R ⁇ , and are shown as mean soil standard deviation (mean SD). Was. The significance test was performed by the t test (pairedttest). “NS” in the table means no significant difference.
  • the eight-catch amount decreased significantly after the first month of administration.
  • the bezafiprate represented by the above formula (I) and a pharmacologically acceptable salt thereof have a hepatobiliary enzyme lowering effect and an HCV growth inhibitory effect, and are markedly inhibited by the present invention against chronic hepatitis C by the present invention. It is possible to provide a therapeutic agent for chronic hepatitis C having an excellent therapeutic effect. Furthermore, the therapeutic agent for chronic hepatitis C of the present invention has an outstanding action effect that it is effective even in cases of intervening ineffectiveness, which is the first-line drug for the treatment of chronic hepatitis C, Suitable for treating chronic hepatitis C.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mechanical Engineering (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur des remèdes pour traiter l'hépatite C chronique contenant un acide α-[4-(4-chlorobenzoylaminoéthyl)phénoxy]isobutyrique comme principe actif dont les effets sont la suppression des enzymes hépatobiliaires et l'inhibition de la prolifération du virus de l'hépatite C. L'acide en question est représenté par la formule (I) ou ses sels pharmaceutiquement acceptables. Ces remèdes ont un effet remarquable même lorsque l'interféron, réputé être le médicament par excellence dans le traitement de l'hépatite C chronique, s'avère inefficace.
PCT/JP2001/007533 2001-02-23 2001-08-31 Remedes pour hepatite c chronique WO2002067920A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001047942A JP4829411B2 (ja) 2001-02-23 2001-02-23 Ｃ型慢性肝炎治療剤
JP2001-47942 2001-02-23

Publications (1)

Publication Number Publication Date
WO2002067920A1 true WO2002067920A1 (fr) 2002-09-06

Family

ID=18909284

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2001/007533 WO2002067920A1 (fr) 2001-02-23 2001-08-31 Remedes pour hepatite c chronique

Country Status (3)

Country Link
JP (1) JP4829411B2 (fr)
KR (1) KR100753709B1 (fr)
WO (1) WO2002067920A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007028424A1 (fr) * 2005-02-15 2007-03-15 F. Hoffmann-La Roche Ag Dérivés d'amides en tant qu’activateurs de ppar

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10130142A (ja) * 1996-10-31 1998-05-19 Zensei Yakuhin Kogyo Kk 放出持続型圧縮製剤
FR2774591B1 (fr) * 1998-02-12 2000-05-05 Lipha Composition pharmaceutique comprenant l'association metformine et fibrate et son utilisation pour la preparation de medicaments destines a reduire l'hyperglycemie

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Amacher David E. et al. "Hepatitic microsomal enzyme induction, bèta-oxidation, and cell proliferation following administration of clofibrate, gemfibrozil, orbezafibrate in the CD rat," Toxicol.Appl.Pharmacol., Vol.142, No.1 (1997), pp. 143-150 *
Kurihara T., et al. "Study of effectiveness of bezafibrate in the treatment of chronic hepatitis C," American Journal of Gastroenterology, Vol.96, No. 5, (May 2001), pp.1659-1660 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007028424A1 (fr) * 2005-02-15 2007-03-15 F. Hoffmann-La Roche Ag Dérivés d'amides en tant qu’activateurs de ppar

Also Published As

Publication number Publication date
JP2002249429A (ja) 2002-09-06
JP4829411B2 (ja) 2011-12-07
KR100753709B1 (ko) 2007-08-30
KR20020069078A (ko) 2002-08-29

Similar Documents

Publication Publication Date Title
JP2617407B2 (ja) 血管内膜細胞過剰増殖疾患の予防および治療剤
US20080096832A1 (en) Method for Improving the Pharmacokinetics of an NNRTI
JP2011140521A (ja) タキサンにより惹起される神経毒性を予防又は軽減するための薬剤
EA014772B1 (ru) Лечение заболеваний печени, в патогенезе которых задействовано железо
AU2002305952A1 (en) Pharmaceutical combinations
JPS59112948A (ja) コレステロ−ルレベル低下剤
JP2004525143A5 (fr)
EP0190851B1 (fr) Composition anti-inflammatoire
CN113557016A (zh) 衣壳组装调节剂固体配制品
JP2006508118A5 (fr)
KR20050016935A (ko) 혈당콘트롤용 의약조성물
IE851848L (en) Propiophenone compound against sexual dysfunction
WO2002067920A1 (fr) Remedes pour hepatite c chronique
EP0218453A1 (fr) Compositions et procédés anti-inflammatoires
WO1996041643A1 (fr) Procede de traitement et agent antiviraux
JPH0415766B2 (fr)
KR100709531B1 (ko) 당뇨병성 합병증의 예방 또는 진전저지용 의약조성물
KR102662826B1 (ko) Hbv 감염 치료를 위한 eyp001 및 ifn의 상승작용 효과
JPH09227371A (ja) 粥状動脈硬化抑制剤
EA046230B1 (ru) Синергическое действие eyp001 и ifn при лечении инфекции hbv
SU1715359A1 (ru) Способ лечени аллергических заболеваний
JPH0867637A (ja) 肝疾患予防治療薬
JPH0753375A (ja) 肝臓疾患治療剤
MXPA01007833A (es) Metodo para prevenir o reducir eventos cardiovasculares asociados con intervencion de la arteria coronaria.
JPS59184124A (ja) 腎不全、糖尿病及び糖尿病性腎症におけるエネルギー代謝改善剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): BG BR BY CA KZ MX PH RO TR UA US

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)