WO1986000529A1 - An antiviral preparation and the method of its production - Google Patents
An antiviral preparation and the method of its production Download PDFInfo
- Publication number
- WO1986000529A1 WO1986000529A1 PCT/HU1985/000040 HU8500040W WO8600529A1 WO 1986000529 A1 WO1986000529 A1 WO 1986000529A1 HU 8500040 W HU8500040 W HU 8500040W WO 8600529 A1 WO8600529 A1 WO 8600529A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- virus
- gumboro
- preparation
- attenuated
- vaccine
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5254—Virus avirulent or attenuated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
- C12N2720/00011—Details
- C12N2720/10011—Birnaviridae
- C12N2720/10032—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
- C12N2720/00011—Details
- C12N2720/10011—Birnaviridae
- C12N2720/10034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Abstract
A biological preparation for the treatment of virus infections, and the procedure of its production. The principle of the method is to combine attenuated Gumboro virus with at least one registered carrier. The preparation which is the object of the invention is characterized by comprising attenuated Gumboro virus.
Description
AN ANTIVIRAL PREPARATION AND THE METHOD OF ITS PRODUC¬TION
Object The object of the invention is a biological preparaion for the treatment of virus infections, object of the invention is also the procedure of its production, and further objects are the use of atte
ed Gumboro virus or Gumboro virus vaccine for treatment of virus infections in humans, and the application of these preparations to humans.
The preparation is suitable for the treatment of practically any virus infection, and is particularly efficient against Herpesvirus infections,
plastic diseases, aphthostomatosis and collagen diseases.
Professional information
Hepatitis virus infection damages the
parenchyma. It has three different forms, known as epidemic hepatitis (hepatitis A virus infection),
hepatitis (hepatitis B virus infection) and non-A-non-B (or C) hepatitis, a condition presumably caused by a hepatitis virus other than A or B. The clinical course of the hepatitis A infection is relatively mild. Latency is usually 10-28 days. The patient is confined to bed for 30-45 days, and disability lasts still longer. The infection evokes specific immunity to further hepatitis A infection but no vaccine is available for prevention.
Hepatitis B infection takes a more serious clinical course, and its latency is also longer, 50 - - 160 days. Virus B is much more resistant to thermic and chemical influences than virus A and most other viruses. Hepatocellular carcinoma is a frequent sequel to hepatitis B infection. This infection does not, as a rule, evoke an immune response. A vaccine prepared from the blood of convalescents is available against hepatitis B, but it has been little used on account of its possible side effects (AIDS) and high price.
As yet no preparation has been available for hepatitis therapy. The purpose of the present invention has therefore been to develop a biological preparation suitable for the therapy and control of viral hepatitis.
Disclosure of the invention
The object of the invention is the development, and method of production of an antiviral preparation containing attenuated Gumboro virus, with or without an adjuvant potentiating the latter's act.ion.
Object of the invention is also the application of the above preparations, and the use of attenuated Gumboro virus, in human therapy.
The Gumboro virus vaccine is known and widely used in the veterinary field.
The Gumboro disease is an acute viral disease of chickens, affecting them mainly at the age of 3-6 weeks. Its main symptoms are watery diarrhea, hyper
trophy of the bursa of Pabricius, and inflammation of the lymphoid organs. In the USA the Gumboro disease, also known as infectious bursitis of chickens, was first described by Congreve in 1957. The disease also occurs in European countries, among others in Hungary. The causal agent of the disease, an enterovirus, is noted for its high resistance. The symptoms set in abruptly after a latency of 2-4 days, and usually subside after a week; most losses occur between days 3 and 5 of the clinical course. In the outbreaks studied, morbidity was 1-30 %, and mortality was 4-5 % .
The Gumboro vaccine, i.e. the attenuated Gumboro virus used by us is prepared by methods known from the literature. Por example, a freeze-dried vaccine is prepared from attenuated virus propagated in primary or secondary fibroblast cultures from 10-11-day chick embryos. Sterile virus material of at least 10 TCID50/0.1 ml titre may be used for production of the vaccine, as prescribed in the Pharm. Hung. VI. To the sterile virus material is added 50 % skim milk, and 2 ml amounts of the vaccine are distributed to 10 ml vials for freeze-drying.
The expiration time of the vaccine is one year when stored in sealed vials at +4 ºC. Safety testing is performed in 15 SPP chickens aged 3 weeks; the birds must not show symptoms within 14 days of vaccination.
The freeze-dried vaccine is delivered in
packing units of 100, 200, 500 and 1000 doses, and is used for prevention of the Gumboro disease. It Is administered orally, in the drinking water.
The vaccine described above is used as active substance of the preparation which is the object of the invention. Naturally the attenuated virus itself, or any solution (e.g. a physiological solution) thereof can also be used for that purpose.
The Gumboro virus is non-pathogenic for man even in its virulent state. Its attenuated form is doubly safe for humans.
Most human vaccines contain inactivated virus, However, the Gumboro vaccine - the object of the invention - is prepared exclusively from attenuated virus. The underlying mechanism of its antiviral action is presumably an interference phenomenon, more precisely a competition between the infecting virus and the vaccine virus.
We observed that the action of the attenuated Gumboro virus was potentiated mainly by certain tranquillizers. Of the latter the drugs of choice are the phenothiazine derivatives substituted usually in positions 2 and 10. Chlorpromazine (10-( 3'-dimethyl-amino-propyl)-2-chloro-phenthiazine) proved to be the most effective compound in this respect. The range of the possible potentiating agents is, naturally, not limited.to phenothiazine-like tranquillizers.
Apart from chlorpromazine, promethazine,
methophenazine, aminopromazine and similar compounds can be used as potentiating agents.
The attenuated virus, component of the preparation which is the object of the invention should preferably be adsorbed onto a common carrier substance.
A freeze-dried vaccine with carrier proved to be the most advantageous, but the preparation can also be delivered in other forms, such as solution, suppository, capsule, emulsion, suspension, etc. The applied dose depends on the patient treated, actual composition of the preparation, stage of disease and virus strain used. Of the attenuated virus 1000 to 5000 U, preferably 3000 - 4000 U, should be used daily either in a single dose or in 2-5 divided doses. Administration on 6 consecutive days is usually sufficient for full effect. Application may be oral or rectal, but where local therapy is required, as in Herpesvirus infections, the preparation car. be applied in the form of solution or ointment. With a potentiating agent added, the dosage also depends on patient, stage of infection and type of causative agent. Por example, chlorpormazine may be administered, at the daily dose level of 10-15 mg. A synergistic preparation should contain 10-100 mg chlorpromazine for each 1000 U of attenuated virus.
The preparations which are the object of the invention have been tested in many animal experiments and human trials, and developed in these a practically
100 % therapeutic effect against both hepatitis A and B, without any toxic side effect. They are suitable not only for symptomatic treatment, but also for prophylactic use: the contact persons of hepatitis A patients, given Gumboro virus preventively within 5 weeks of latency, did not contract the infection.
Further animal experiments and clinical trials in virus infections other than hepatitis have revealed the therapeutic efficiency of the preparations against many virus diseases.
The most promising results were obtained in the following conditions:
- Herpesvirus infections such as herpes simplex I, II, herpes zooster., cytomegalovirus disease, infectious mononucleosis (Epstein-Barr virus);
- various viral neoplastic diseases, above all liver cancer;
- aphthostomatosis;
- collagen diseases, e.g. polyarteritis nodosa.
Claims
1. Procedure for the production of a biological preparation against virus diseases, c h a r a c t e r i z e d by combination of attenuated Gumboro virus with at least one registered carrier.
2. Procedure according to claim 1, c h a r a c t e r i z e d by addition of a potentiating agent to the preparation.
3. Procedure according to claim 2, c h a r a c t e r i z e d by addition of chlorpromazine for potentiation.
4. Antiviral preparation c h a r a c t e r i z e d by comprising attenuated Gumboro virus.
5. Antiviral preparation according to Claim 4, c h a r a c t e r i z e d by comprising a registered carrier.
6. Preparation according to claim 4 and/or claim 5, c h a r a c t e r i z e d by comprising a potentiating agent.
7. Preparation according to claim 6, c h a r a c t e r i z e d by comprising chlorpromazine as potentiating agent.
8. Application of attenuated Gumboro virus or Gumboro virus vaccine for therapy of virus infections in humans.
9. Treatment of human virus infections with Gumboro vaccine or attenuated Gumboro virus.
10. Treatment of hepatitis with Gumboro vaccine or attenuated Gumboro virus.
11. The treatment according to claims 9 and 10, c h a r a c t e r i z e d by using a potentiating agent.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HU3616/83 | 1984-07-02 | ||
HU833616A HU197846B (en) | 1984-07-02 | 1984-07-02 | Process for producing therapeutic composition suitable for treating virus infections |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1986000529A1 true WO1986000529A1 (en) | 1986-01-30 |
Family
ID=10964798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/HU1985/000040 WO1986000529A1 (en) | 1984-07-02 | 1985-07-01 | An antiviral preparation and the method of its production |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0188499A1 (en) |
AU (1) | AU4549385A (en) |
HU (1) | HU197846B (en) |
WO (1) | WO1986000529A1 (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5602023A (en) * | 1992-03-24 | 1997-02-11 | Csatary; Laszlo K. | Pharmaceutical product containing live, stabilized virus for the therapy of viral and malignant diseases and process for preparing the same |
US7056689B1 (en) | 1993-04-30 | 2006-06-06 | Wellstat Biologics Corporation | Methods of treating and detecting cancer using viruses |
WO2008068661A1 (en) * | 2006-12-01 | 2008-06-12 | Hepc Biotechnológiai Kutató És Fejleszto Kft. | Compositions and methods for the treatment of viral hepatitis |
US7470426B1 (en) | 1997-10-09 | 2008-12-30 | Wellstat Biologics Corporation | Treatment of neoplasms with viruses |
US7780962B2 (en) | 1997-10-09 | 2010-08-24 | Wellstat Biologics Corporation | Treatment of neoplasms with RNA viruses |
US8043612B2 (en) | 1997-10-09 | 2011-10-25 | Wellstat Biologics Corporation | Infection and treatment of neoplasms with vesicular stomatitis virus |
US8105578B2 (en) | 1997-10-09 | 2012-01-31 | Wellstat Biologics Corporation | Treatment of neoplasms with viruses |
US8147822B1 (en) | 1999-09-17 | 2012-04-03 | Wellstat Biologics Corporation | Oncolytic virus |
US8377450B2 (en) | 2009-11-30 | 2013-02-19 | United Cancer Research Institute | Clone of Newcastle disease virus, its manufacture and its application in the medical treatment of cancer |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0713397B1 (en) * | 1992-03-24 | 2002-12-11 | United Cancer Research Institute | Vaccine containing live virus |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3548055A (en) * | 1969-05-14 | 1970-12-15 | Research Corp | Infectious bursal disease vaccine |
AT308967B (en) * | 1970-09-12 | 1973-07-25 | Behringwerke Ag | Method of making a live vaccine |
US3885011A (en) * | 1971-12-29 | 1975-05-20 | Janssen Pharmaceutica Nv | Vaccine adjuvants |
DD143793A1 (en) * | 1979-03-12 | 1980-09-10 | Ursula Schmidt | METHOD FOR THE PRODUCTION OF A VACCINE AGAINST THE INFEKTIOESE BURSITIS OF POULTRY |
-
1984
- 1984-07-02 HU HU833616A patent/HU197846B/en unknown
-
1985
- 1985-07-01 AU AU45493/85A patent/AU4549385A/en not_active Abandoned
- 1985-07-01 WO PCT/HU1985/000040 patent/WO1986000529A1/en unknown
- 1985-07-01 EP EP85903351A patent/EP0188499A1/en not_active Withdrawn
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3548055A (en) * | 1969-05-14 | 1970-12-15 | Research Corp | Infectious bursal disease vaccine |
AT308967B (en) * | 1970-09-12 | 1973-07-25 | Behringwerke Ag | Method of making a live vaccine |
US3885011A (en) * | 1971-12-29 | 1975-05-20 | Janssen Pharmaceutica Nv | Vaccine adjuvants |
DD143793A1 (en) * | 1979-03-12 | 1980-09-10 | Ursula Schmidt | METHOD FOR THE PRODUCTION OF A VACCINE AGAINST THE INFEKTIOESE BURSITIS OF POULTRY |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5602023A (en) * | 1992-03-24 | 1997-02-11 | Csatary; Laszlo K. | Pharmaceutical product containing live, stabilized virus for the therapy of viral and malignant diseases and process for preparing the same |
US7056689B1 (en) | 1993-04-30 | 2006-06-06 | Wellstat Biologics Corporation | Methods of treating and detecting cancer using viruses |
US7736640B2 (en) | 1993-04-30 | 2010-06-15 | Wellstat Biologics Corporation | Methods of treating and detecting cancer using viruses |
US7470426B1 (en) | 1997-10-09 | 2008-12-30 | Wellstat Biologics Corporation | Treatment of neoplasms with viruses |
US7780962B2 (en) | 1997-10-09 | 2010-08-24 | Wellstat Biologics Corporation | Treatment of neoplasms with RNA viruses |
US8043612B2 (en) | 1997-10-09 | 2011-10-25 | Wellstat Biologics Corporation | Infection and treatment of neoplasms with vesicular stomatitis virus |
US8105578B2 (en) | 1997-10-09 | 2012-01-31 | Wellstat Biologics Corporation | Treatment of neoplasms with viruses |
US8147822B1 (en) | 1999-09-17 | 2012-04-03 | Wellstat Biologics Corporation | Oncolytic virus |
WO2008068661A1 (en) * | 2006-12-01 | 2008-06-12 | Hepc Biotechnológiai Kutató És Fejleszto Kft. | Compositions and methods for the treatment of viral hepatitis |
US8398969B2 (en) | 2006-12-01 | 2013-03-19 | HepC Biotechnológiai Kutató és Fejlesztö Kft. | Compositions and methods for the treatment of viral hepatitis |
US8377450B2 (en) | 2009-11-30 | 2013-02-19 | United Cancer Research Institute | Clone of Newcastle disease virus, its manufacture and its application in the medical treatment of cancer |
Also Published As
Publication number | Publication date |
---|---|
HU197846B (en) | 1989-06-28 |
HUT47223A (en) | 1989-02-28 |
AU4549385A (en) | 1986-02-10 |
EP0188499A1 (en) | 1986-07-30 |
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