MXPA00001205A - Product comprising at least a double stranded rna combined with at least an antiviral agent - Google Patents
Product comprising at least a double stranded rna combined with at least an antiviral agentInfo
- Publication number
- MXPA00001205A MXPA00001205A MXPA/A/2000/001205A MXPA00001205A MXPA00001205A MX PA00001205 A MXPA00001205 A MX PA00001205A MX PA00001205 A MXPA00001205 A MX PA00001205A MX PA00001205 A MXPA00001205 A MX PA00001205A
- Authority
- MX
- Mexico
- Prior art keywords
- product according
- hepatitis
- dsrna
- interferon
- viral hepatitis
- Prior art date
Links
- 229920000160 (ribonucleotides)n+m Polymers 0.000 title claims abstract description 38
- 239000003443 antiviral agent Substances 0.000 title claims abstract description 29
- 108020004461 Double-Stranded RNA Proteins 0.000 title claims abstract description 10
- 230000001225 therapeutic Effects 0.000 claims abstract description 11
- 102000014150 Interferons Human genes 0.000 claims description 35
- 108010050904 Interferons Proteins 0.000 claims description 35
- 229940079322 interferon Drugs 0.000 claims description 25
- 206010019799 Hepatitis viral Diseases 0.000 claims description 19
- 201000001862 viral hepatitis Diseases 0.000 claims description 19
- 229940047124 Interferons Drugs 0.000 claims description 10
- 208000002672 Hepatitis B Diseases 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 208000005176 Hepatitis C Diseases 0.000 claims description 8
- 229920000320 RNA (poly(A)) Polymers 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000001684 chronic Effects 0.000 claims description 5
- 241000700605 Viruses Species 0.000 claims description 4
- 230000002035 prolonged Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 1
- 230000000875 corresponding Effects 0.000 claims 1
- 208000001756 Virus Disease Diseases 0.000 abstract description 13
- 208000006454 Hepatitis Diseases 0.000 abstract description 5
- 231100000283 hepatitis Toxicity 0.000 abstract description 4
- 230000035492 administration Effects 0.000 description 21
- 239000000203 mixture Substances 0.000 description 14
- 108020004412 RNA 3' Polyadenylation Signals Proteins 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- JTEGQNOMFQHVDC-NKWVEPMBSA-N 4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 5
- 229960001627 Lamivudine Drugs 0.000 description 5
- 229960000329 Ribavirin Drugs 0.000 description 5
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 5
- BXZVVICBKDXVGW-NKWVEPMBSA-N ddIno Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 4
- 229960002656 didanosine Drugs 0.000 description 4
- PMATZTZNYRCHOR-CGLBZJNRSA-N (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17 Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 230000002519 immonomodulatory Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229960002170 Azathioprine Drugs 0.000 description 2
- 229940119017 Cyclosporine Drugs 0.000 description 2
- 229960002963 Ganciclovir Drugs 0.000 description 2
- IRSCQMHQWWYFCW-UHFFFAOYSA-N Ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 108010002335 Interleukin-9 Proteins 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N Prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 229960003636 Vidarabine Drugs 0.000 description 2
- 230000001154 acute Effects 0.000 description 2
- 230000000840 anti-viral Effects 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000002354 daily Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- ZTHWFVSEMLMLKT-CAMOTBBTSA-N vidarabine monohydrate Chemical compound O.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O ZTHWFVSEMLMLKT-CAMOTBBTSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2R,3R,4S,5R,6S)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2S,3R,4S,5R,6R)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2R,3R,4S,5R,6R)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 208000006154 Chronic Hepatitis C Diseases 0.000 description 1
- 206010008909 Chronic hepatitis Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000005252 Hepatitis A Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 206010019773 Hepatitis G Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 229940047122 Interleukins Drugs 0.000 description 1
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 description 1
- KNUXHTWUIVMBBY-JRJYXWDASA-N Rintatolimod Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1.O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1.O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 KNUXHTWUIVMBBY-JRJYXWDASA-N 0.000 description 1
- 210000002966 Serum Anatomy 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H Tricalcium phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 206010047461 Viral infection Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000000699 topical Effects 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 230000003612 virological Effects 0.000 description 1
- 230000003442 weekly Effects 0.000 description 1
Abstract
The invention concerns a product comprising at least a double stranded RNA (RNAdb) combined with at least an antiviral agent for therapeutic use in the treatment of a viral disease, in particular different types of hepatitis.
Description
- | Í? * É
- * 7 * L
PRODUCT THAT CONTIER? Líy? LESS ONE DOUBLE HEBREW RNA IN COMBINATION WITH AT LEAST AN ANTIVIRAL AGENT Description of the invention: - The present invention relates to a product that contains at least one double-stranded RNA
(ARNds_L in combination with at least one antiviral agent, preferably an interferon, for therapeutic use, simultaneously, separately or in a period of time, in the treatment of a viral disease.) Such a product can be used in particular for the treatment of hepatitis The Applicant has found that the combination of dsRNA with an antiviral agent, and in particular with an interferon, results in an unexpected smérgico effect in the treatment of viral infections, in particular in the treatment of viral hepatitis. both an object of the invention is a product containing at least one dsRNA in combination with at least one antiviral agent for therapeutic use, simultaneously, separately or in a period of time, in the treatment of a viral disease. it is preferably understood a complex of polyadenyl ico acid with acid REF .: 32733 polyuridyl, also known as poly (A) -poly (U) or Poly-adenur®. Other dsRNAs can be used for the invention, in particular a complex of polyinosinic acid with polycytidylic acid, also known as poly (I) -poly (C), as well as these same complexes modified by the introduction of uridic acid within the chain of polycyclic acid, such as the product Ampligen® manufactured by the company HEMISPHERx (for a description of these products see in particular European Patent Application EP-0, 300, 580). The dsRNA used can be, for example, a mixture of dsRNAs as defined above. The dsRNAs are preferably prepared according to the procedure described in French Patent No. 2, 622, 586. In the present application, the term "antiviral agent" is understood to mean an agent acting directly on the virus, such as ribavirin. or lamivudine, and an immunomodulatory agent, for example an agent that weakens or strengthens immune defenses, such as cyclosporin or an interferon.The antiviral agents combined with the dsRNA can be chosen, for example, from an interferon, such as interferons a , ß or? or consensus interferons, and in particular, an interferon-a (INF-a), other lymphokines, such as interleukins, for example IL6 or IL9, ganciclovir, cumermicin Al, lamivudine, ribavirin, vidarabine, dideoxyinosine (DDI) ), azathioprine, prednisolone or cyclosporine.Preferably, the antiviral agent combined with the dsRNA will be an interferon.An interferon is understood to be one or more interferons to different, such as for example Interferons a-2a, a-2b, a-2c, a-ni, a-n3, or any other analog that has comparable immunological properties. By a consensus interferon is understood, for example, the interferons INF-conl, INF-con2 and INF-con3 (these consensus interferons are described in particular in U.S. Patent No. 5,372,808 and in PCT / O Patent Application 93 / 21229). By simultaneous therapeutic use is meant in the present Application, an administration of more active ingredients by the same route and at the same time. By separate use is meant, in particular, an administration of several active ingredients at about the same time by different routes. By therapeutic administration over a period of time it is understood the administration of several
é? active ingredients at different times and in particular a method of administration to which the entire administration of one of the active ingredients is completed, before the administration of the other or of the others begins. In this way it is possible to administer one of the active ingredients for several months before administering the other or other active ingredients. In this case, simultaneous administration does not occur. Viral disease is understood in particular as viral hepatitis, and in particular hepatitis B or hepatitis C. Viral hepatitis treated with the product according to the invention may be chronic or acute in nature. Preferably, the product according to the invention is intended for chronic hepatitis. The invention in particular relates to a product that is characterized in that it comprises: i) a dsRNA in combination with: n) an antiviral agent, for prolonged therapeutic use over a period of time, in the treatment of a viral disease. Preferably, the use of the dsRNA takes place before the antiviral agent.
According to a preferred variant of the invention, the invention relates to a product that is characterized in that it comprises: i) a dsRNA in combination with ii) an interferon for prolonged therapeutic use over a period of time in the treatment of a disease viral. Preferably, the use of dsRNA takes place before the inferred. Preferably the interferon used will be interferon a. According to a particular aspect of the invention, the product contains at least one dsRNA in combination with at least one antiviral agent, which can be a mmunomodulatory agent and is characterized in that it also contains at least one antiviral agent that acts directly on viruses for the simultaneous or separate use with the immunomodulatory agent or agents in the treatment of a viral disease. Preferably, the immunomodulatory agent (s) are interferons. According to another variant of the invention, the product containing at least one dsRNA in combination with at least one antiviral agent is characterized in that it also contains at least one antiviral agent for therapeutic use that is
extends over a "" period of time, and that takes place before the dsRNA in the treatment of a viral disease. Among the others, antiviral Uagents which can be used for this particular variant of the invention, there can be mentioned lymphokines different from interferons such as the methylleucins, for example, IL-6 or IL-9, ganciclovir, cumermicin Al, lamivudine, ribavirin, vidarabine, dideoxyinosine (DDI), azathioprine, prednisolone or cyclosporine. More particularly, the invention relates to a product characterized in that it comprises: i) an antiviral agent in combination with li) a dsRNA, and in) an inferred, which may be simultaneously or separately combined with an antiviral agent that acts directly on the viruses, for an administration that is separated in time and carried out in the order indicated above in the treatment of a viral disease, in particular hepatitis B. The various sequences of administration of the dsRNA and the antiviral agent can be considered. According to a particular method of + - &
the invention, the dsRNA and the antiviral are not administered simultaneously. Preferably, the dsRNA is administered before the antiviral agent with which it is combined. The treatment with the dsRNA preferably extends over a period of 1 to 12 months or more, for example 6 months, and followed by administration of the antiviral agent in an equivalent or different period of time. An object of the invention is also pharmaceutical compositions containing, as an active ingredient, a product according to the invention, for example a product containing at least one dsRNA in combination with at least one antiviral agent, preferably an interferon, in combination with excipients or supports suitable for therapeutic use simultaneously, separately or in a period of time, in the treatment of viral diseases. Preferably, the viral disease treated by the pharmaceutical products and the compositions according to the invention will be viral hepatitis, such as hepatitis A, B, C or G or hepatitis' not A, not B, not C, not G " for example hepatitis of a different type to types A, B, C or G. The products and pharmaceutical compositions according to
The invention is directed in particular to the treatment of hepatitis B or hepatitis C. In addition, viral hepatitis treated with the products and pharmaceutical compositions according to the invention can take the form of acute or chronic viral hepatitis and will preferably consist of chronic viral hepatitis. The viral hepatitis treated with the products and pharmaceutical compositions according to the invention will be particularly preferably chronic hepatitis B or C. The pharmaceutical compositions containing a product according to the invention can be in the form of a solid., for example powders, granules, tablets, capsules, liposomes or suppositories. Suitable solid supports can be, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidine or wax. Pharmaceutical compositions containing a product according to the invention can be presented in the form of a liquid, for example solutions, emulsions, suspensions or syrups. Appropriate liquid supports can
fefct-? "IfcSM be, for example, water, organic solvents, such as glycerol or glycols, as well as their mixtures, in various proportions, in water. Finally, the invention relates to a product according to the invention, for example a product containing at least one dsRNA and at least one antiviral agent, for manufacturing a medicament for the treatment of viral diseases, and in particular viral hepatitis. Preferably, the viral disease treated by the product according to the invention will be hepatitis B or hepatitis C. Preferably, the antiviral agent combined with the dsRNA is an interferon. An interferon α (INF-cc) will be very particularly preferred. The method of administration of the product according to the invention is chosen from conventional administration methods. For example, administration of the dsRNA can take place, for example, by the topical route, oral or parenteral, by intravenous or intramuscular injection, or by the subcutaneous route. Similarly, antiviral agents can be administered by the same routes. For each of these compounds, a
A person skilled in the art will select the appropriate administration method. The administration dose considered by the medicament according to the invention is between 5 0.1 mg and 10 g per administration, depending on the type of active compound used. In the case of dsRNA, in particular that of poly (A) -poly (U), a dose can preferably be considered between 10 mg and 3 g per
doses The product can be administered daily or several times a week. For example, a dose of between 15 mg and 1.5 g can be administered, preferably of the order of 50 to 300 mg two or three times per week. The dose of interferon will in theory be that usually used by a person skilled in the art, and preferably between 0.5 and 60 million international units per dose. In the case of INF-a, for example, the dose may be
between 1 and 50 million units, preferably between 1 and 10, and in particular between 3 and 6 million units. In addition, the administration can be daily or take place several times a week. In particular, two or more may be administered per week
three administrations. For example, it is possible
Choose to manage between 3 and 6 million units two or three times a week. According to another variant of the invention, it is also possible to precede the treatment with dsRNA by a treatment with an antiviral agent. For example, an interferon, lamivudine or ribavirin could be administered during the first period, the dsRNA during a second period and finally during a third period, an interferon optionally combined with at least one antiviral agent, such as ribavirin or lamivudine. The interferon used for the treatment will preferably be an INF-a. To choose the methods and dosage of administration, a person skilled in the art could also usefully consult the following article (and the references cited therein): Daniel Dhumeaux, La rev? E du pra ct i ci en, 45 pp. 2519-2522 (1995). Unless defined otherwise, all technical and scientific terms used herein have the same meanings as those generally understood by the ordinary specialist in the field to which this invention pertains. Similarly, all publications, patent applications, all patents and all other references mentioned herein are incorporated by reference.
Clinical properties of the products according to the invention
Example 1
A group of ten patients suffering from hepatitis C was treated successively with poly (A) poly (U) and then with interferon. The treatment was carried out as follows: initially, patients received two weekly administrations of a 150 mg dose of poly (A) poly (U) administered by the intravenous route for 24 weeks; After this initial treatment, patients received a dose of 3 million units of interferon, administered by the intravenous route 3 times per week for 24 weeks. After this two-stage treatment, a remission of the disease was observed in 6 of the patients, a remission followed by a relapse in a seventh patient and the treatment had no effect only in three of the patients.
? ? "A» r
By way of comparison, a treatment consisting of interferon alone, produced remission in only 20% to 30% of the treated cases (see Daniel Dhumeaux, La revue du pra cti ci en, 45 PP 2519- 5 2522 (1995).
Example 2
Two groups of patients suffering from
chronic active hepatitis B, the first group consisting of 42 patients (group A), the second group consisting of 44 patients (group B) received the following treatments, starting on the same date: 15 - patients in group A received a dose of 150 mg of poly (A) -poly (U) administered by the intravenous route twice a week for 24 weeks, and then a dose of 6 million units of INF-a administered by the route
Subcutaneously, 3 times a week for the next 24 weeks; patients in group B did not receive treatment for the first 24 weeks and then received 6 million units of INF-a
üs ^ y¡XhMtí L? &. ^ ..
administered by the subcutaneous route 3 times a week for the next 24 weeks. The presence of HBV virus DNA and a serum HBe test were determined 24, 48 and 72 weeks after the date when treatment with poly (A) -poly (U) was started. The results, expressed in terms of the percentage of patients who responded to the treatment, are summarized in the following table:
+ P 0.001 p = 0.02 p = 0.006
Conclusion: in patients suffering from chronic, active hepatitis B, pretreatment with poly (A) -poly (U) before treatment with INF-a had the result of increasing the proportion of response to treatment for 6 months with INF- a and reduced the number of relapses after this treatment.
It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.
Claims (15)
1. A product, characterized in that it comprises at least one double-stranded RNA (dsRNA) in association with at least one interferon for a prolonged therapeutic use over time, in the treatment of a viral hepatitis.
2. The product according to claim 1, characterized in that the use of the dsRNA takes place before that of the interferon.
3. The product according to claim 1, characterized in that the dsRNA is the polyadenylic acid formed in complex with the polyuridylic acid.
4. The product according to claim 1, characterized in that the dsRNA is an I, J7 : &7 »polyinosinic acid complex with polyidiidic acid.
5. The product according to any of claims 1, 3 or 4, characterized in that the interferon is chosen from the interferons a, β and γ. or the corresponding consensus interferons.
6. The product according to claim 5, characterized in that the interferon is an interferon a (INF-a).
7. The product according to any of claims 1 to 6, characterized in that it also comprises at least one other antiviral agent for a therapeutic use prolonged in time, and prior to that of dsRNA in the treatment of a viral hepatitis.
8. The product according to claim 7, characterized in that it comprises: i) an antiviral agent, in association with ii) a dsRNA, and iii) an interferon possibly associated simultaneously or separately "with an antiviral agent that acts directly on the viruses for a administration separated in time and carried out in the order indicated above in the treatment of a viral hepatitis.
9. The product according to any of claims 1 to 8, characterized in that the viral hepatitis is a chronic viral hepatitis.
10. The product according to any of claims 1 to 8, characterized in that the viral hepatitis is hepatitis B.
11. The product according to any of claims 1 to 8, characterized in that the viral hepatitis is hepatitis C.
12. A pharmaceutical composition, characterized in that it comprises, as an active principle, a product according to any of claims 1 to 11, in association with the appropriate excipients or carriers.
13. The use of a product according to any of claims 1 to 11, for manufacturing a medicament for treating viral hepatitis.
14. The use according to claim 13, characterized in that the viral hepatitis is hepatitis B.
15. The use according to claim 13, characterized in that the viral hepatitis is hepatitis C.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR97/09975 | 1997-08-04 | ||
| FR97/10644 | 1997-08-26 | ||
| FR97/11543 | 1997-09-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA00001205A true MXPA00001205A (en) | 2001-11-21 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU750026B2 (en) | Product comprising at least a double stranded RNA combined with at least an antiviral agent | |
| EP0286224B1 (en) | Treatment of human viral infection by dsrna combined with viral inhibitors | |
| MXPA06004077A (en) | Combination therapy for hcv infection. | |
| JP2004507496A5 (en) | ||
| Northfelt | Treatment of Kaposi’s sarcoma: current guidelines and future perspectives | |
| JP3838034B2 (en) | Hepatitis C therapeutic effect improving agent and its application | |
| MXPA00001205A (en) | Product comprising at least a double stranded rna combined with at least an antiviral agent | |
| CA2141951C (en) | Inhibition of retrovirus infection | |
| RU2217161C2 (en) | Method for treatment of viral hepatitis | |
| JP2000007578A (en) | Medication system for turning hepatitis c virus negative | |
| EP0344643B1 (en) | Antiviral pharmaceutical composition | |
| AU2006339220B2 (en) | Pharmaceutical composition for treatment of blood clotting disorder | |
| CZ2000336A3 (en) | Product containing at least one RNA with two filaments together with at least one antiviral agent | |
| JP2003527414A (en) | Drugs for treating hepatitis C | |
| JPH10251159A (en) | Medicine for decreasing serum uric acid value, containing il-6 | |
| FR2768345A1 (en) | Composition containing double-stranded RNA and interferon | |
| EP1587531A2 (en) | Hcv combination therapy | |
| FR2768344A1 (en) | Composition containing double-stranded RNA and interferon | |
| Battelli et al. | ACTH 1–17 effects in oncology | |
| JPH11130693A (en) | Medicine for feline aids viral infectious disease and its treatment | |
| FR2766715A1 (en) | Product containing synergistic mixture of double-stranded RNA and antiviral agent | |
| TW201247217A (en) | New treatments of Hepatitis C virus infection | |
| DE19640054A1 (en) | Di:nucleotide(s) with modified base, sugar and phosphate groups |