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WO2001070203A2 - Agent for treating hepatitis c containing ukrain - Google Patents

Agent for treating hepatitis c containing ukrain Download PDF

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Publication number
WO2001070203A2
WO2001070203A2 PCT/AT2001/000076 AT0100076W WO0170203A2 WO 2001070203 A2 WO2001070203 A2 WO 2001070203A2 AT 0100076 W AT0100076 W AT 0100076W WO 0170203 A2 WO0170203 A2 WO 0170203A2
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ukrain
patients
ifn
hepatitis
doses
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German (de)
French (fr)
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WO2001070203A3 (en
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Wassyl Nowicky
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Priority to KR1020027005739A priority Critical patent/KR20020087045A/en
Priority to PL01365000A priority patent/PL365000A1/en
Priority to JP2001568401A priority patent/JP2003527414A/en
Priority to MXPA02004993A priority patent/MXPA02004993A/en
Priority to HR20020367A priority patent/HRP20020367A2/en
Priority to IL14931401A priority patent/IL149314A0/en
Priority to CA002389173A priority patent/CA2389173A1/en
Priority to EA200200584A priority patent/EA200200584A1/en
Priority to BR0107211-0A priority patent/BR0107211A/en
Application filed by Individual filed Critical Individual
Priority to AU2001239000A priority patent/AU2001239000A1/en
Publication of WO2001070203A2 publication Critical patent/WO2001070203A2/en
Priority to IS6360A priority patent/IS6360A/en
Priority to NO20022253A priority patent/NO20022253D0/en
Publication of WO2001070203A3 publication Critical patent/WO2001070203A3/en
Priority to BG107088A priority patent/BG107088A/en
Anticipated expiration legal-status Critical
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    • 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

Definitions

  • the present invention relates to the use of phosphorus derivatives of alkaloids for the manufacture of a medicament for the treatment of hepatitis C.
  • hepatitis C means a disease that has only been researched for a relatively short time. For a long time it was only known that there is a disease here that causes symptoms similar to the hepatitis A and hepatitis B diseases known to date, but that there are certain significant differences in the form of the disease. For a long time, the disease was therefore characterized as "hepatitis non-A non-B".
  • Hepatitis C is a disease that is particularly prevalent in underdeveloped countries; It is believed that around 170 million people worldwide (i.e. approximately 4 times the amount of HIV infections) are infected with hepatitis C.
  • AT 377 988 B and AT 354 644 B describe processes for the preparation of new phosphorus derivatives of alkaloids or of new salts of alkaloid derivatives of thiophosphoric acid. Such compounds have pharmacological activity and can be used as cytostatics.
  • the object of the present invention is therefore the use of the reaction product of the alkaloids of Chelidonium majus L. with thiophosphoric acid triaziridide for the manufacture of a medicament for combating hepatitis C.
  • Ukrain The above-mentioned implementation product will be briefly referred to below as "Ukrain"; the overwhelming majority of Ukrain has the following formula:
  • IFN was tested in doses of 20, 50, 100, 200, 400, 600, 1000 IU / l blood, Ukrain in doses of 0.05, 0.1, 0.2, 0.5, 1.0 and 2, 0 ⁇ g / ml blood.
  • Ten of the CHC patients examined were selected for the clinical Pilot trial with individual optimal IFN doses (0.5 to 2.0 ME (unit of measure) per injection, 6 patients, including 3 cases of HCV phenotype la) three times a week and Ukrain doses (0.25 to 2.5 mg per injection, 4 patients, including 2 HCV lb cases) every other day.
  • the responses to the two compositions were shown to be different: 52.5% of all patients were sensitive to IFN and 73.1% to Ukrain, with the increase in the SH / SS ratio under the influence of the compositions being positive Effect and the reduction was assessed as a negative effect. Some patients have already shown a positive effect on the first dose of the preparations, others only on two or more doses.
  • the optimal biological response to IFN in doses of 400, 200 and 100 IU / ml blood and to Ukrain in doses of 0.5, 0.1 and 0.2 ⁇ g / l blood was recorded more frequently.
  • Standardized therapeutic IFN doses of 600 to 1000 IU / ml which correspond to in vivo injections of 3.0 to 5.0 ME doses, only showed a positive effect on the SH / SS system in 0 to 18.2% of the cases and a negative effect in 63.6 to 81.8% of cases, which is one of the reasons for the low effectiveness of IFN in CHC and the frequency of side effects in IFN therapy.
  • 9 out of 10 patients were HCV-RNA negative in PCR: 3 after one month, 3 after three months of therapy with an individual IFN dose, 3 after three weeks of individual therapy with Ukrain. No serious side effects have been identified and treatment of all patients is ongoing.
  • the response to Ukrain was shown to be different: 73.1% of all patients were sensitive to this composition, while in the same group of CHC patients, sensitivity to interferon-alpha 2b (IFN) was significantly lower, namely 46 2%. In the group of CHC patients who were IFN-resistant, the sensitivity to Ukrain was almost the same (71.4%). Furthermore, all 4 CHC patients with HCV phenotype lb were sensitive to Ukrain in vitro. The optimal biological response to Ukrain doses of 0.5, 0.1 and 0.2 ⁇ g / ml blood was frequently recorded.
  • IFN interferon-alpha 2b
  • the medicaments produced according to the invention preferably consist of an aqueous solution of the alkaloid phosphor derivatives or their salts used, optionally together with other auxiliaries known per se.
  • the medicament according to the invention is preferably administered by injection, for example intraperitoneally, intramuscularly or intravenously, the dosage depending on the case and being related to the severity of the disease to be treated and the condition of the patient.

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

Abstract

Disclosed is the use of the conversion product of the alkaloides of Chelidonium majus L. with thiophosphoric acid triaziridide for producing a medicament for treating hepatitis C.

Description

Mittel zur Behandlung von Hepatitis C Agent for the treatment of hepatitis C.

Die vorliegende Erfindung betrifft die Verwendung von Phosphorderivaten von Alkaloiden zur Herstellung eines Arzneimittels zur Behandlung von Hepatitis C.The present invention relates to the use of phosphorus derivatives of alkaloids for the manufacture of a medicament for the treatment of hepatitis C.

Unter der Bezeichnung Hepatitis C wird eine Krankheit verstanden, die erst seit relativ kurzer Zeit erforscht ist. Man war sich lange Zeit lediglich bewusst, dass hier zwar eine Krankheit vorliegt, die ähnliche Krankheitsbilder hervorruft wie die bisher bekannten Krankheiten Hepatitis A und Hepatitis B, dass jedoch in der Erscheinungsform gewisse wesentliche Unterschiede bestehen. Lange Zeit wurde die Erkrankung daher unter der Bezeichnung "Hepatitis non-A non-B" charakterisiert.The term hepatitis C means a disease that has only been researched for a relatively short time. For a long time it was only known that there is a disease here that causes symptoms similar to the hepatitis A and hepatitis B diseases known to date, but that there are certain significant differences in the form of the disease. For a long time, the disease was therefore characterized as "hepatitis non-A non-B".

Hepatitis C ist eine Krankheit, die insbesondere in unterentwickelten Ländern weit verbreitet ist; es wird angenommen, dass weltweit etwa 170 Mio. Menschen (d.i. etwa die 4-fache Menge der HIV-Infektionen) mit Hepatitis C infiziert sind.Hepatitis C is a disease that is particularly prevalent in underdeveloped countries; It is believed that around 170 million people worldwide (i.e. approximately 4 times the amount of HIV infections) are infected with hepatitis C.

Inzwischen konnte erforscht werden, dass das Hepatitis C-Virus zur Familie der Flaviviridae gehört, und es werden weltweit große Anstrengungen unternommen, Mittel zur Prophylaxe bzw. zur Bekämpfung dieser Krankheit zu entwickeln.It has now been researched that the hepatitis C virus belongs to the Flaviviridae family, and great efforts are being made worldwide to develop means of preventing or combating this disease.

Die AT 377 988 B und die AT 354 644 B beschreiben Verfahren zur Herstellung von neuen Phosphorderivaten von Alkaloiden bzw. von neuen Salzen von Alkaloidderivaten von Thiophosphorsäure. Derartige Verbindungen besitzen eine pharmakologische Wirksamkeit und können als Cytostatika Verwendung finden.AT 377 988 B and AT 354 644 B describe processes for the preparation of new phosphorus derivatives of alkaloids or of new salts of alkaloid derivatives of thiophosphoric acid. Such compounds have pharmacological activity and can be used as cytostatics.

Es wurde nun überraschend gefunden, dass von den in den genannten Patentschriften beschriebenen Substanzen insbesondere das Umsetzungsprodukt der Alkaloide von Chelidonium majus L. mit Thiophos- phorsäuretriaziridid zur Bekämpfung von Hepatitis C eingesetzt werden kann, und dass mit einem derartigen Mittel ausgezeichnete Ergebnisse erzielt werden können.It has now surprisingly been found that of the substances described in the patents mentioned, in particular the reaction product of the alkaloids of Chelidonium majus L. with thiophosphoric triaziridide can be used to combat hepatitis C, and that excellent results can be achieved with such an agent.

Gegenstand der vorliegenden Erfindung ist daher die Verwendung des Umsetzungsproduktes der Alkaloide von Chelidonium majus L. mit Thiophosphorsäuretriaziridid zur Herstellung eines Arzneimittels zur Bekämpfung von Hepatitis C.The object of the present invention is therefore the use of the reaction product of the alkaloids of Chelidonium majus L. with thiophosphoric acid triaziridide for the manufacture of a medicament for combating hepatitis C.

Das oben genannte Umsetzungsprodukt soll im Folgenden kurz als "Ukrain" bezeichnet werden; der weitaus überwiegende Hauptbestandteil von Ukrain weist die folgende Formel auf:The above-mentioned implementation product will be briefly referred to below as "Ukrain"; the overwhelming majority of Ukrain has the following formula:

Figure imgf000003_0001
Figure imgf000003_0001

Es wurden Untersuchungen durchgeführt, bei denen einerseits Ukrain in Mischung mit Interferon-alpha und andererseits Ukrain allein eingesetzt wurden. Im Folgenden sollen beide Versuchsreihen beschrieben werden:Investigations were carried out using Ukrain mixed with interferon-alpha and Ukrain alone. Both test series are described below:

1. Einsatz von Interferon-alpha und Ukrain Verfahren1. Use of interferon-alpha and Ukrain methods

Die Wirkung von rekombinantem, humanem Interferon-alpha2b (IFN) und Ukrain (halbsynthetische Verbindung von Chelidonium majus L . Alkaloiden und Thiophosphorsäuretriazirididen, NSC-631570, "Nowicky Pharma", Österreich) wurde in vitro auf das Thiol-Disul- fid-Verhältnis (SH/SS) des Blutes (Patent der Russischen Föderation 2150700) durch amperometrisches Titrationsverfahren getestet. 40 CHC-Patienten wurden untersucht. IFN wurde in Dosen von 20, 50, 100, 200, 400, 600, 1000 IE/ l Blut getestet, Ukrain in Dosen von 0,05, 0,1, 0,2, 0,5, 1,0 und 2,0 μg/ml Blut. Zehn der untersuchten CHC-Patienten wurden ausgewählt für den klinischen Pilot-Versuch mit individuellen optimalen IFN-Dosen (0,5 bis 2,0 ME (Maßeinheit) pro Injektion, 6 Patienten, einschließlich 3 Fälle HCV Phenotyp la) drei Mal die Woche und Ukrain-Dosen (0,25 bis 2,5 mg pro Injektion, 4 Patienten, einschließlich 2 HCV lb-Fäl- len) jeden zweiten Tag.The effect of recombinant, human interferon-alpha 2b (IFN) and Ukrain (semi-synthetic compound of Chelidonium majus L. alkaloids and thiophosphoric triaziridides, NSC-631570, "Nowicky Pharma", Austria) was in vitro on the thiol-disulfide ratio (SH / SS) of the blood (patent of the Russian Federation 2150700) tested by amperometric titration. 40 CHC patients were examined. IFN was tested in doses of 20, 50, 100, 200, 400, 600, 1000 IU / l blood, Ukrain in doses of 0.05, 0.1, 0.2, 0.5, 1.0 and 2, 0 μg / ml blood. Ten of the CHC patients examined were selected for the clinical Pilot trial with individual optimal IFN doses (0.5 to 2.0 ME (unit of measure) per injection, 6 patients, including 3 cases of HCV phenotype la) three times a week and Ukrain doses (0.25 to 2.5 mg per injection, 4 patients, including 2 HCV lb cases) every other day.

Es wurde gezeigt, dass die Reaktionen auf beide Zusammensetzungen unterschiedlich waren: 52,5% aller Patienten waren auf IFN empfindlich und 73,1% auf Ukrain, wobei die Erhöhung des SH/SS-Ver- hältnisses unter dem Einfluss der Zusammensetzungen als eine positive Wirkung und die Verringerung als eine negative Wirkung eingeschätzt wurde. Einige Patienten haben bereits auf die erste Dosis der Präparationen eine positive Wirkung gezeigt, andere erst auf zwei oder mehr Dosen. Häufiger wurde die optimale biologische Antwort auf IFN in Dosen von 400, 200 und 100 IE/ml Blut, auf Ukrain in Dosen von 0,5, 0,1 und 0,2 μg/ l Blut registriert. Standardisierte therapeutische IFN-Dosen von 600 bis 1000 IE/ml, die in vivo Injektionen von 3,0 bis 5,0 ME Dosen entsprechen, zeigten eine positive Wirkung auf das SH/SS-System lediglich in 0 bis 18,2% der Fälle und eine negative Wirkung in 63,6 bis 81,8% der Fälle, was einer der Gründe für die geringe Wirksamkeit von IFN in CHC und die Häufigkeit von Nebenwirkungen in der IFN-The- rapie ist. Fast die Hälfte aller CHC-Patienten waren gegenüber IFN resistent (47,5%), einschließlich der vier Fälle mit nachgewiesenem HCV-Phenotyp Ib. Nach der individuellen Therapie mit IFN oder Ukrain waren 9 von 10 Patienten HCV-RNA negativ in PCR: 3 nach einem Monat, 3 nach dreimonatiger Therapie mit individueller IFN-Dosis, 3 nach dreiwöchiger individueller Therapie mit Ukrain. Es wurden keine ernsthaften Nebenwirkungen festgestellt, die Behandlung aller Patienten wird weitergeführt.The responses to the two compositions were shown to be different: 52.5% of all patients were sensitive to IFN and 73.1% to Ukrain, with the increase in the SH / SS ratio under the influence of the compositions being positive Effect and the reduction was assessed as a negative effect. Some patients have already shown a positive effect on the first dose of the preparations, others only on two or more doses. The optimal biological response to IFN in doses of 400, 200 and 100 IU / ml blood and to Ukrain in doses of 0.5, 0.1 and 0.2 μg / l blood was recorded more frequently. Standardized therapeutic IFN doses of 600 to 1000 IU / ml, which correspond to in vivo injections of 3.0 to 5.0 ME doses, only showed a positive effect on the SH / SS system in 0 to 18.2% of the cases and a negative effect in 63.6 to 81.8% of cases, which is one of the reasons for the low effectiveness of IFN in CHC and the frequency of side effects in IFN therapy. Almost half of all CHC patients were resistant to IFN (47.5%), including the four cases with proven HCV phenotype Ib. After individual therapy with IFN or Ukrain, 9 out of 10 patients were HCV-RNA negative in PCR: 3 after one month, 3 after three months of therapy with an individual IFN dose, 3 after three weeks of individual therapy with Ukrain. No serious side effects have been identified and treatment of all patients is ongoing.

Auf der Basis von diesen erhaltenen Daten konnte ein Verfahren zur Selektion von Patienten bereits vor der Therapie, die von der Therapie mit IFN oder Ukrain in bestimmten optimalen Dosen profitieren können, und Patienten, die nicht darauf ansprechen und die mit anderen Medikamenten behandelt werden müssen, zur Verfügung gestellt werden. Die individuelle Therapie wird die Effizienz der CHC-Behandlung erhöhen, die Anzahl von Nebenwirkungen verringern und die Therapiekosten günstiger gestalten (z.B. für die IFN-The- rapie betragen sie das 3- bis 5-Fache) . 2. Einsatz von Ukrain alleine VerfahrenOn the basis of the data obtained, a procedure for the selection of patients before therapy who could benefit from therapy with IFN or Ukrain in certain optimal doses and patients who did not respond and who had to be treated with other medications could be to provide. The individual therapy will increase the efficiency of the CHC treatment, reduce the number of side effects and make the therapy costs cheaper (eg for the IFN therapy they are 3 to 5 times). 2. Use of Ukrain alone procedure

Die Wirkung von Ukrain (halbsynthetische Verbindung von Chelidonium majus L . Alkaloiden und Thiophosphorsäure-triazirididen, NSC-631570, "Nowicky Pharma", Österreich) auf das Thiol-Disulfid- Verhältnis (SH/SS) von Blut (Patent der Russischen" Förderation 2150700) wurde in vitro durch ein amperometrisches Titrationsverfahren getestet. 26 CHC Patienten wurden untersucht. Ukrain wurde in Dosen von 0,05, 0,1, 0,2, 0,5, 1,0 und 2,0 μg/ml Blut getestet. Für den klinischen Pilot-Versuch mit individuellen optimalen Ukrain-Dosen (0,25 bis 2,5 mg pro Injektion) wurden jeden zweiten Tag 4 CHC-Patienten (2 unbehandelte Patienten und 2 Patienten mit nachgewiesenem HCV-Phenotyp lb, die ursprünglich mit Interferonalpha erfolglos behandelt wurden) ausgewählt.The effect of Ukrain (semi-synthetic compound of Chelidonium majus L. alkaloids and thiophosphoric acid triaziridides, NSC-631570, "Nowicky Pharma", Austria) on the thiol-disulfide ratio (SH / SS) of blood (patent of the Russian "Federation 2150700 ) was tested in vitro by an amperometric titration method, 26 CHC patients were examined and Ukrain was tested in doses of 0.05, 0.1, 0.2, 0.5, 1.0 and 2.0 μg / ml blood. For the clinical pilot trial with individual optimal Ukrain doses (0.25 to 2.5 mg per injection), 4 CHC patients (2 untreated patients and 2 patients with proven HCV phenotype lb, originally with interferon alpha) were examined every other day treated unsuccessfully).

Es wurde nachgewiesen, dass die Reaktion auf Ukrain unterschiedlich war: 73,1% aller Patienten waren auf diese Zusammensetzung empfindlich, während in der selben Gruppe von CHC-Patienten die Empfindlichkeit auf Interferon-alpha2b (IFN) wesentlich geringer war, nämlich 46,2%. In der Gruppe der CHC-Patienten, die IFN re- sistent waren, war die Empfindlichkeit auf Ukrain fast gleich (71,4%), weiters waren alle 4 CHC-Patienten mit HCV-Phenotyp lb in vitro auf Ukrain empfindlich. Häufig wurde die optimale biologische Antwort auf Ukrain-Dosen von 0,5, 0,1 und 0,2 μg/ml Blut registriert. Im klinischen Versuch konnten wir bereits nach 10 Ukrain-Injektionen eine positive klinische, biochemische (Verringerung der ALT (Alanintransaminase) in allen 4 Fällen) und viro- logische Antwort (PCR HCV-RNA war in 3 Fällen negativ, einschließlich ein Fall mit HCV lb) feststellen. In zwei Fällen ging eine Erhöhung der ALT nach Beginn der Ukrain-Therapie der Verringerung der ALT voraus (einschließlich einem anderen Fall mit HCV lb, wobei ALT mehr als 3-fach verringert war) . Das serologische SH/SS-Verhältnis nach der Ukrain-Therapie erhöhte sich in drei Fällen mit biochemischer und virologischer Antwort und verringerte sich in dem Fall ohne virologischer Antwort. Keine Nebeneffekte wurden festgestellt. Die Behandlung dieser vier Patienten wird weitergeführt .The response to Ukrain was shown to be different: 73.1% of all patients were sensitive to this composition, while in the same group of CHC patients, sensitivity to interferon-alpha 2b (IFN) was significantly lower, namely 46 2%. In the group of CHC patients who were IFN-resistant, the sensitivity to Ukrain was almost the same (71.4%). Furthermore, all 4 CHC patients with HCV phenotype lb were sensitive to Ukrain in vitro. The optimal biological response to Ukrain doses of 0.5, 0.1 and 0.2 μg / ml blood was frequently recorded. In the clinical trial, we were able to give a positive clinical, biochemical (reduction in ALT (alanine transaminase) in all 4 cases) and virological response (PCR HCV-RNA was negative in 3 cases, including one case with HCV lb) after only 10 Ukrain injections ) determine. In two cases, an increase in ALT after starting Ukrain therapy preceded a decrease in ALT (including another case with HCV lb, where ALT was more than 3-fold decreased). The serological SH / SS ratio after Ukrain therapy increased in three cases with a biochemical and virological response and decreased in the case without a virological response. No side effects were found. The treatment of these four patients will continue.

Eine hohe Ansprechrate von CHC-Patienten auf Ukrain in vitro wur- de festgestellt (1,58-fach höher als IFN) und es besteht keine Kreuzresistenz zwischen Ukrain und IFN. Selbst Patienten mit HCV- Phenotyp lb sind auf Ukrain empfindlich sowohl in vitro als auch in vivo. Eine individuelle Therapie von CHC mittels Ukrain scheint sowohl für noch unbehandelte Patienten als auch für Patienten, die resistent sind oder nach IFN alleine oder in Kombination mit Ribavirin einen Rückfall erleiden, wirksam zu sein. Auf der Basis dieser Ergebnisse können spezielle klinische Versuche mit Ukrain zur Behandlung von CHC-Patienten begonnen werden.A high response rate of CHC patients to Ukrain in vitro has been de determined (1.58 times higher than IFN) and there is no cross resistance between Ukrain and IFN. Even patients with HCV phenotype lb are sensitive to Ukrain both in vitro and in vivo. Individual treatment of CHC with Ukrain appears to be effective both for untreated patients and for patients who are resistant or who relapse after IFN alone or in combination with ribavirin. Based on these results, special clinical trials with Ukrain can be started to treat CHC patients.

Die erfindungsgemäß hergestellten Arzneimittel bestehen vorzugsweise aus einer wässerigen Lösung der verwendeten Alkaloidphos- phorderivate bzw. deren Salze, gegebenenfalls zusammen mit weiteren, an sich bekannten Hilfsstoffen. Die Verabreichung des erfindungsgemäßen Arzneimittels erfolgt dabei bevorzugt durch Injektion, beispielsweise intraperitoneal, intramuskulär oder intravenös, wobei die Dosierung fallabhängig ist und mit der Schwere der zu behandelnden Erkrankung sowie dem Zustand des Patienten zusammenhängt .The medicaments produced according to the invention preferably consist of an aqueous solution of the alkaloid phosphor derivatives or their salts used, optionally together with other auxiliaries known per se. The medicament according to the invention is preferably administered by injection, for example intraperitoneally, intramuscularly or intravenously, the dosage depending on the case and being related to the severity of the disease to be treated and the condition of the patient.

Es liegt jedenfalls im Fachwissen des behandelnden Arztes, eine geeignete Dosierung von Fall zu Fall zu bestimmen. In any case, it is within the specialist knowledge of the attending physician to determine a suitable dosage from case to case.

Claims

P a t e n t a n s p r ü c h e : Patent claims: 1. Verwendung des Umsetzungsproduktes der Alkaloide von Chelidonium majus L. mit Thiophosphorsäuretriaziridid zur Herstellung eines Arzneimittels zur Bekämpfung von Hepatitis C1. Use of the reaction product of the alkaloids of Chelidonium majus L. with thiophosphoric acid triaziridide for the manufacture of a medicament for combating hepatitis C. 2. Verwendung nach Anspruch 1, dadurch gekennzeichnet, dass das Umsetzungsprodukt zusammen mit anderen Wirksubstanzen, insbesondere Interferon-alpha, eingesetzt wird. 2. Use according to claim 1, characterized in that the reaction product is used together with other active substances, in particular interferon-alpha.
PCT/AT2001/000076 2000-03-22 2001-03-20 Agent for treating hepatitis c containing ukrain Ceased WO2001070203A2 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
BR0107211-0A BR0107211A (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c
JP2001568401A JP2003527414A (en) 2000-03-22 2001-03-20 Drugs for treating hepatitis C
MXPA02004993A MXPA02004993A (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c containing ukrain.
HR20020367A HRP20020367A2 (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c
IL14931401A IL149314A0 (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c
CA002389173A CA2389173A1 (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c
EA200200584A EA200200584A1 (en) 2000-03-22 2001-03-20 MEANS FOR THE TREATMENT OF HEPATITIS C
KR1020027005739A KR20020087045A (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c
AU2001239000A AU2001239000A1 (en) 2000-03-22 2001-03-20 Agent for treating hepatitis C containing Ukrain
PL01365000A PL365000A1 (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c containing ukrain
IS6360A IS6360A (en) 2000-03-22 2002-04-24 Medicines for the treatment of hepatitis C
NO20022253A NO20022253D0 (en) 2000-03-22 2002-05-10 Agent for the treatment of hepatitis C
BG107088A BG107088A (en) 2000-03-22 2002-09-12 Agent for treating hepatitis c

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT0048100A AT408719B (en) 2000-03-22 2000-03-22 AGENT FOR TREATING HEPATITIS C
ATA481/2000 2000-03-22

Publications (2)

Publication Number Publication Date
WO2001070203A2 true WO2001070203A2 (en) 2001-09-27
WO2001070203A3 WO2001070203A3 (en) 2002-09-06

Family

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PCT/AT2001/000076 Ceased WO2001070203A2 (en) 2000-03-22 2001-03-20 Agent for treating hepatitis c containing ukrain

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

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003041721A1 (en) * 2001-11-15 2003-05-22 Nowicky Wassili Process for reacting alkaloids and use of the reaction products in the preparation of medicaments
EP2083825A4 (en) * 2006-09-26 2009-11-04 Addiction Res Inst Inc Compositions for the treatment of hepatitis c and methods for using compositions for the treatment of hepatitis c
US7795434B2 (en) 2003-03-18 2010-09-14 Wassyl Nowicky Quaternary chelidonine and alkaloid derivatives, process for their preparation and their use in manufacture of medicaments

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106343303A (en) * 2015-07-13 2017-01-25 张如安 Beverage for killing hepatitis B virus
CN106109538A (en) * 2016-07-29 2016-11-16 桂林淮安天然保健品开发有限公司 The pharmaceutical composition for the treatment of hepatitis C

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3128018A1 (en) * 1981-07-13 1983-04-07 Wassyl 1060 Wien Nowicky "METHOD FOR DIAGNOSTICING AND FOR THE THERAPEUTIC TREATMENT OF TUMORS AND / OR INFECTIOUS DISEASES OF DIFFERENT TYPES WITH PREPARATIVE USE OF ALKALOID COMPOUNDS OR THEIR SALTS"
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 (en) * 1989-04-17 1991-01-08 Searle & Co PROCESS FOR THE PREPARATION OF COMPOSITIONS FOR THE TREATMENT OF NEOPLASMS, CONTAINING AN ANTI-NEOPLASTIC AGENT, FOR EXAMPLE DOXORUBICIN AND A PROTEIN AGENT TO REDUCE THE SIDE EFFECTS, FOR EXAMPLE CARBETIMER

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003041721A1 (en) * 2001-11-15 2003-05-22 Nowicky Wassili Process for reacting alkaloids and use of the reaction products in the preparation of medicaments
JP2005509006A (en) * 2001-11-15 2005-04-07 ノヴィッキイ、 ヴァジル Production method for reacting alkaloids and use of reaction product pharmaceutical preparation
CN100436462C (en) * 2001-11-15 2008-11-26 挪威奇·华兹 Reaction method of alkaloid, reaction product and application thereof
US7795434B2 (en) 2003-03-18 2010-09-14 Wassyl Nowicky Quaternary chelidonine and alkaloid derivatives, process for their preparation and their use in manufacture of medicaments
EP2083825A4 (en) * 2006-09-26 2009-11-04 Addiction Res Inst Inc Compositions for the treatment of hepatitis c and methods for using compositions for the treatment of hepatitis c

Also Published As

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PL365000A1 (en) 2004-12-27
NO20022253L (en) 2002-05-10
KR20020087045A (en) 2002-11-21
JP2003527414A (en) 2003-09-16
MXPA02004993A (en) 2003-10-14
CA2389173A1 (en) 2001-09-27
MA25509A1 (en) 2002-07-01
ATA4812000A (en) 2001-07-15
HRP20020367A2 (en) 2004-02-29
CN1416347A (en) 2003-05-07
NO20022253D0 (en) 2002-05-10
WO2001070203A3 (en) 2002-09-06
EA200200584A1 (en) 2003-06-26
AT408719B (en) 2002-02-25
IL149314A0 (en) 2002-11-10
AU2001239000A1 (en) 2001-10-03
BG107088A (en) 2003-05-30
IS6360A (en) 2002-04-24
BR0107211A (en) 2004-01-06

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