CN1416347A - 治疗丙肝的药剂 - Google Patents

治疗丙肝的药剂 Download PDF

Info

Publication number
CN1416347A
CN1416347A CN01803046A CN01803046A CN1416347A CN 1416347 A CN1416347 A CN 1416347A CN 01803046 A CN01803046 A CN 01803046A CN 01803046 A CN01803046 A CN 01803046A CN 1416347 A CN1416347 A CN 1416347A
Authority
CN
China
Prior art keywords
ukrain
patient
treatment
ifn
hepatitis
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.)
Pending
Application number
CN01803046A
Other languages
English (en)
Inventor
瓦塞伊·诺威基
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.)
WASSY NOWICKY
Original Assignee
WASSY NOWICKY
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 WASSY NOWICKY filed Critical WASSY NOWICKY
Publication of CN1416347A publication Critical patent/CN1416347A/zh
Pending legal-status Critical Current

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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]
    • A61K38/212—IFN-alpha
    • 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
    • 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

Landscapes

  • 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)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

本发明公开了白屈菜生物碱与硫代磷酸氮丙啶化物(triaziridide)的反应产物在制备用于治疗丙肝的药物中的用途。

Description

治疗丙肝的药剂
本发明涉及生物碱的磷衍生物在制备用于治疗丙肝的药物中的用途。
“丙肝”是指近期研究的一种疾病。在很长时间内人们只知道其是一种与已知的甲肝、乙肝具有类似症状的疾病，但是在表现上存在某些基本的差别。因此，很长时间内，人们把这种疾病称为“非甲非乙肝”。
丙肝尤其在不发达国家中非常普遍；据估计，在全世界范围内大约有1.7亿人口(即，大约是HIV感染人数的4倍)感染有丙肝。
同时，可以发现丙肝病毒是B族虫媒病毒(flaviviridae)族的一员，全世界都致力于开发用于预防和治疗这种疾病的药剂。
AT377988B和AT354644B分别公开了生产新的生物碱磷衍生物和新的生物碱硫代磷酸盐的衍生物的方法。这类化合物具有药理活性，并且可以用作细胞生长抑制剂。
令人惊奇的是，现在发现在这些特别提到的专利说明书所述的物质中白屈菜(chelidonium majus L.)的生物碱与硫代磷酸氮丙啶化物(triaziridide)的反应产物可用于治疗丙肝，且使用这种药剂可获得出色的效果。
因此，本发明涉及白屈菜的生物碱与硫代磷酸氮丙啶化物的反应产物在制备用于治疗丙肝的药物中的用途。
以下，将上述反应产物称为“Ukrain”，目前Ukrain的主要成份的通式如下：
在已经进行的试验中，一方面是Ukrain与α干扰素混合使用，另一方面是Ukrain单独使用。以下，将对这两类试验进行描述。
1.α干扰素与Ukrain混合使用。
方法
通过电流滴定法测定血液中硫羟-二硫化物的比例(SH/SS)(俄联邦专利2150700)以体外测试人体α2b干扰素(IFN)与Ukrain(白屈菜生物碱与硫代磷酸氮丙啶化物(triaziridide)的半合成化合物，NSC-631570，“Nowicky Pharma”，奥地利)的重组体的效果。40名CHC-患者参加了测试，IFN的测试剂量为20，50，100，200，400，600，1000U/ml血液，Ukrain的测试剂量为0.05，0.1，0.2，0.5，1.0和2.0μg/ml血液。选择参加测试的CHC患者中的10人进行临床试验测试，每名患者每周三次施用最佳的IFN剂量(每次注射0.5-2.0MU(测量单位)，6名患者，包括3例HCV-显型1a)，以及每隔一天施用Ukrain剂量(每次注射0.5-2.5mg，4名患者，包括两例2HCV1b)。
结果表明，对于这两种药的反应是不同的：全部患者中有52.5％对IFN敏感，73.1％对Ukrain敏感，在这两种药影响下SH/SS比值提高被认为具有积极的效果，而该比值降低被认为具有负面影响。某些患者在施用第一个剂量时即已产生积极的效果，其他的患者则需要两个或更多的剂量。更为常见的是，最佳生物反应对于IFN是出现在剂量为400，200和100IU/ml血液时，对于Ukrain是在剂量为0.5，0.1和0.2μg/ml血液时。600-1000IU/ml的标准IFN治疗剂量对应于3.5-5.0MU的体内注射剂量，对于SH/SS系统有积极效果的病例仅为0-18.2％，而有负面影响的病例占63.6-81.8％，这是IFN对CHC效果较差的一个原因，也是IFN治疗中经常出现副作用的一个原因。所有CHC患者中接近半数(47.5％)对IFN有抗药性，包括4例已得到证明的HCV表型1b的患者。当患者单独使用IFN或Ukrain进行治疗后，10名患者中的9名在PCR中HCV-RNA呈阴性：一个月后有3人，单独使用IFN剂量治疗三个月后有3人，单独使用Ukrain治疗三周后3人。未发现严重副作用。继续对全部患者进行治疗。
基于以上得到的数据，可为治疗前的选择提供一种方法，以确定哪些患者能受益于某些最佳剂量的IFN治疗或Ukrain治疗，以及哪些患者对其无反应和哪些患者必须使用不同的药物进行处治。用单独一种治疗可以提高CHC治疗的效率，减少副作用并使治疗的成本-效果更佳(例如，对IFN治疗的成本是3-5倍)。
2.单独使用Ukrain
方法
通过电流滴定法体外测试Ukrain(白屈菜生物碱与硫代磷酸氮丙啶化物的半合成化合物，NSC-631570，“Nowicky Pharma”，奥地利)对血液中硫羟-二硫化物的比例(SH/SS)(俄联邦专利2150700)的影响。26名CHC-患者参加了测试。Ukrain的测试剂量为0.05，0.1，0.2，0.5，1.0和2.0μg/ml血液。对于进行Ukrain最佳个体剂量(每次注射0.25-2.5mg)的临床试验测试，每隔一天选出4名患者(未进行处理的患者2名，2名患者被证明患有HCV表型1b，开始时使用α干扰素进行治疗不成功)。
结果表明，对于Ukrain有不同的反应：全部患者中73.1％对这种组分敏感，而在同一CHC患者组中对α2b干扰素(IFN)敏感性相当低，即46.2％。在对IFN有抗药性的CHC患者组中，对Ukrain敏感性的几乎相同(71.4％)，而且，全部4名患有HCV-表型1b的CHC患者体外试验均对Ukrain敏感。通常，对于Ukrain的最佳生物反应出现在剂量为0.5，0.1和0.2μg/ml血液。在临床测试中进行10次Ukrain注射后，我们已经发现在临床学、生物化学(全部四个病例中ALT(丙氨酸转氨酶)的降低)和病毒学反应(三个病例中PCR HCV-RNA为阴性，包括一例为HCV1b)上为阳性。在两个病例中，在Ukrain治疗发挥作用后，ALT先升高，而后ALT降低(包括另外一例HCV1b，其中ALT降低超过3倍)。Ukrain治疗后，伴有生物化学和病毒学反应的三个病例的血清SH/SS比值升高，而无病毒学响应的病例该比值降低。未发现副作用。对这四名患者继续治疗。
体外测得了CHC患者对Ukrain的高的反应率(高于IFN1.5倍)，且在Ukrain和IFN之间无交叉抗药性。即使患有HCV-表型1b的患者也对Ukrain敏感，无论体外或体内。使用Ukrain的CHC的个体治疗看来无论对未处理过的患者、或对单独使用IFN或同时使用三(氮)唑核苷后有抗药性或复发的患者均有效。基于这些结果，可以用Ukrain对CHC患者的治疗进行特定临床试验。
本发明所制得药剂优选包含一种生物碱磷衍生物或其盐的水溶液，或者视情况可与本来已知的辅助物质联合。本发明药剂优选的给药方式为注射，例如，腹膜内、肌肉内或静脉内，剂量取决于病例且与所处理病情的严重性及患者状态有关。
但是，视病例不同决定适合的用药量是在医师的专业知识范围内的。

Claims (2)

1.白屈菜生物碱与硫代磷酸氮丙啶化物的反应产物在制备用于治疗丙肝的药物中的用途。
2.如权利要求1的用途，其特点在于该反应产物与其他活性物质一同使用，特别是与α干扰素一同使用。
CN01803046A 2000-03-22 2001-03-20 治疗丙肝的药剂 Pending CN1416347A (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT0048100A AT408719B (de) 2000-03-22 2000-03-22 Mittel zur behandlung von hepatitis c
ATA481/2000 2000-03-22

Publications (1)

Publication Number Publication Date
CN1416347A true CN1416347A (zh) 2003-05-07

Family

ID=3674939

Family Applications (1)

Application Number Title Priority Date Filing Date
CN01803046A Pending CN1416347A (zh) 2000-03-22 2001-03-20 治疗丙肝的药剂

Country Status (17)

Country Link
JP (1) JP2003527414A (zh)
KR (1) KR20020087045A (zh)
CN (1) CN1416347A (zh)
AT (1) AT408719B (zh)
AU (1) AU2001239000A1 (zh)
BG (1) BG107088A (zh)
BR (1) BR0107211A (zh)
CA (1) CA2389173A1 (zh)
EA (1) EA200200584A1 (zh)
HR (1) HRP20020367A2 (zh)
IL (1) IL149314A0 (zh)
IS (1) IS6360A (zh)
MA (1) MA25509A1 (zh)
MX (1) MXPA02004993A (zh)
NO (1) NO20022253D0 (zh)
PL (1) PL365000A1 (zh)
WO (1) WO2001070203A2 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106109538A (zh) * 2016-07-29 2016-11-16 桂林淮安天然保健品开发有限公司 治疗丙肝的药物组合物

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH695417A5 (de) * 2001-11-15 2006-05-15 Ddr Wassyl Nowicky Dipl Ing Verfahren zur Umsetzung von Alkaloiden.
EP1459753A1 (en) 2003-03-18 2004-09-22 Nowicky, Wassyl, Dipl.-Ing. DDr. Quaternary chelidonine and alkaloid derivatives, process for their preparation and their use in the manufacture of medicaments
CA2664935A1 (en) * 2006-09-26 2008-04-03 Addiction Research Institute, Inc. Compositions for the treatment of hepatitis c and methods for using compositions for the treatment of hepatitis c
CN106343303A (zh) * 2015-07-13 2017-01-25 张如安 灭杀乙肝病毒的饮料

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3128018A1 (de) * 1981-07-13 1983-04-07 Wassyl 1060 Wien Nowicky "verfahren zum diagnostizieren und fuer die therapeutische behandlung von tumoren und/oder infektioesen krankheiten verschiedenster art unter praeparativem einsatz von alkaloid-verbindungen bzw. deren salze"
US4816462A (en) * 1982-05-18 1989-03-28 Nowicky Wassili Method for diagnosing and for the therapeutic treatment of tumors and/or infectious diseases of different types with alkaloid-compounds
US4970212A (en) * 1982-05-18 1990-11-13 Nowicky Wassili Method of treating human illnesses which compromise the ability to mount an effective immunological response
PT93772A (pt) * 1989-04-17 1991-01-08 Searle & Co Processo para a preparacao de composicoes para o tratamento de neoplasias, contendo um agente anti-neoplastico, por exemplo doxorubicina e um agente protector para reduzir os efeitos secundarios, por exemplo carbetimer

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106109538A (zh) * 2016-07-29 2016-11-16 桂林淮安天然保健品开发有限公司 治疗丙肝的药物组合物

Also Published As

Publication number Publication date
CA2389173A1 (en) 2001-09-27
KR20020087045A (ko) 2002-11-21
IS6360A (is) 2002-04-24
NO20022253L (no) 2002-05-10
BR0107211A (pt) 2004-01-06
PL365000A1 (en) 2004-12-27
NO20022253D0 (no) 2002-05-10
BG107088A (en) 2003-05-30
MXPA02004993A (es) 2003-10-14
WO2001070203A2 (de) 2001-09-27
AU2001239000A1 (en) 2001-10-03
HRP20020367A2 (en) 2004-02-29
JP2003527414A (ja) 2003-09-16
EA200200584A1 (ru) 2003-06-26
AT408719B (de) 2002-02-25
WO2001070203A3 (de) 2002-09-06
MA25509A1 (fr) 2002-07-01
IL149314A0 (en) 2002-11-10
ATA4812000A (de) 2001-07-15

Similar Documents

Publication Publication Date Title
EP0858343B1 (en) Continuous low-dose cytokine infusion therapy
RU2271217C2 (ru) ПРИМЕНЕНИЕ ПЭГ-ИНТЕРФЕРОНА-α(ПЭГ-IFN-α) И РИБАВИРИНА ДЛЯ ЛЕЧЕНИЯ ХРОНИЧЕСКОГО ГЕПАТИТА С
Silva et al. A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE)
Di Bisceglie et al. Therapy of chronic hepatitis B with recombinant human alpha and gamma interferon
Moscarella et al. Interferon and thymosin combination therapy in naive patients with chronic hepatitis C: preliminary results
RU2007105354A (ru) Применение комбинации циклоспорина и пэгилированного интерферона для лечения гепатита с (hcv)
Pockros Developments in the treatment of chronic hepatitis C
CN1416347A (zh) 治疗丙肝的药剂
CN1087829A (zh) 治疗乙肝的组合物及其方法
CA2380653A1 (en) Mycophenolate mofetil in association with peg-ifn-.alpha.
Barbaro et al. Intravenous recombinant interferon-beta versus interferon-alpha-2b and ribavirin in combination for short-term treatment of chronic hepatitis C patients not responding to interferon-alpha
Fujiwara et al. Randomized control trial of interferon-β injections at 12-h intervals as a therapy for chronic hepatitis C
US20010046957A1 (en) Method for treating hepatitis C
CA2614639C (en) Pharmaceutical composition for treatment of blood clotting disorder
Abbas et al. Thymosin alpha 1 in combination with interferon alpha and ribavirin in chronic hepatitis C patients who are non-responders or relapsers to interferon alpha plus ribavirin
CN105749246A (zh) 治疗丙肝病毒感染的阿拉泊韦
KR20050101184A (ko) 에이치씨이브이 조합 요법
US20040191216A1 (en) Medicines including interferon and administering system thereof
Jeffries et al. Quantitative PCR< IO00 cp/m! at treatment week 24 Group1 (n= 78) Group 2 (n= 74) Total (n= 152)
JPH07188049A (ja) 代謝不全肝疾患の患者の治療のための方法および組成物
CA2405547C (en) Protective agent against reinfection after liver transplantation
Vermehren et al. CLONAL ANALYSIS OF MUTATIONS SELECTED IN THE HCV NS3 PROTEASE DOMAIN OF GENOTYPE 1 NONRESPONDERS SEQUENTIALLY TREATED WITH BOCEPREVIR (SCH503034) AND/OR PEGYLATED INTERFERON ALFA-2B (PEG-IFN α-2B): 1592
Sarin What should we advise about adjunctive therapies, including herbal medicines, for hepatitis C?
Carnicer et al. Tratamiento con PEG interferón alfa 2b y ribavirina en enfermos previamente tratados con interferón estándar en monoterapia o combinado con ribavirina
Ben-Noun Interferon Therapy in Liver Cirrhosis Type C

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication