WO1992004909A1 - Pharmaceutical composition comprising cd4 and a polyanionic anti-hiv agent and use thereof - Google Patents
Pharmaceutical composition comprising cd4 and a polyanionic anti-hiv agent and use thereof Download PDFInfo
- Publication number
- WO1992004909A1 WO1992004909A1 PCT/GB1991/001627 GB9101627W WO9204909A1 WO 1992004909 A1 WO1992004909 A1 WO 1992004909A1 GB 9101627 W GB9101627 W GB 9101627W WO 9204909 A1 WO9204909 A1 WO 9204909A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- agent
- hiv
- polyanionic
- virus
- effective dose
- Prior art date
Links
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 title claims abstract description 20
- 229940124411 anti-hiv antiviral agent Drugs 0.000 title claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 34
- 239000000463 material Substances 0.000 claims abstract description 24
- 241000700605 Viruses Species 0.000 claims abstract description 19
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 16
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 13
- 229920001282 polysaccharide Polymers 0.000 claims description 12
- 239000005017 polysaccharide Substances 0.000 claims description 12
- 229920001353 Dextrin Polymers 0.000 claims description 11
- 239000004375 Dextrin Substances 0.000 claims description 11
- 235000019425 dextrin Nutrition 0.000 claims description 11
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 10
- 150000004676 glycans Chemical class 0.000 claims description 9
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 4
- 230000036436 anti-hiv Effects 0.000 claims description 3
- -1 sulphat polysaccharide Chemical class 0.000 claims description 3
- 150000001720 carbohydrates Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 229920000447 polyanionic polymer Polymers 0.000 claims 1
- 208000031886 HIV Infections Diseases 0.000 abstract description 8
- 208000037357 HIV infectious disease Diseases 0.000 abstract description 6
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 abstract description 6
- 239000000654 additive Substances 0.000 abstract description 3
- 230000000996 additive effect Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 7
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 108010041884 CD4 Immunoadhesins Proteins 0.000 description 1
- 241000518994 Conta Species 0.000 description 1
- 241000501458 Cultus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229920000855 Fucoidan Polymers 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- GIXWDMTZECRIJT-UHFFFAOYSA-N aurintricarboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=CC1=C(C=1C=C(C(O)=CC=1)C(O)=O)C1=CC=C(O)C(C(O)=O)=C1 GIXWDMTZECRIJT-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 229960005314 suramin Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- 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
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
Definitions
- This invention relates to pharmaceutically active compositi and to their use as agents against human immunodeficiency vi and related viruses.
- the HIV infection cycle includes a number of steps, each of th steps being a possible target for the use of chemotherapy hinder the infection.
- the first step in the infection cycle the attachment of the HIV virus to the host cell.
- the m receptor for the virus is believed to be the cell surf glycoprotein, designated CD4, which is present in some lymphocytes and in some macrophages. Much attention therefore been given to identifying agents which are capable blocking attachment of the virus to CD4.
- statin CD4 made by genetic engineering, can block attachment of H virus to cellular CD4, thereby inhibiting HIV infection in vitr
- CD4-li materials capable of binding to gpl20, such as CD4-Ig immunoadhesins, CD4 V1-V2 domains, and CD4-derived peptides, ha also been proposed as anti-HIV agents.
- CD4-Ig immunoadhesins CD4 V1-V2 domains
- CD4-derived peptides ha also been proposed as anti-HIV agents.
- the performan of CD4 and CD4-like materials in preventing the HIV virus fr binding to cells has until now been disappointing, a much high concentration of the agent being necessary than had been hoped.
- anti-HIV agents which block attachment of the virus cells are a number of polyanionic compounds which include Eva Blue, aurintricarboxylic acid (ATA), suramin, and certai sulphated polysaccharides. It might have been thought that i CD4 and such polyanionic anti-HIV agents were use simultaneously, the total anti-HIV activity would at best be th sum of their separate activities.
- CD4 which is used here an below, except where otherwise indicated, to include both CD4 an CD4-like materials
- a polyanionic anti-HIV agent such as a sulphated polysaccharide
- the invention provides an agent against HIV an related viruses, in dosage unit form, comprising CD4 or a CD4 like material and a polyanionic anti-HIV agent the content of CD and CD4-like material in the agent being less than the anti virally effective dose of the CD4 or CD4-like material alone.
- the agent according to the invention may contain substantiall less CD4 than the anti-virally effective dosage of CD4 alo i.e. in the absence of a polyanionic anti-HIV agent.
- reduction in the amount of CD4 required to achieve the same an viral effect as for CD4 alone may be such that less than o tenth (or, in favourable cases, less than one-hundredth) of amount of CD4 is needed.
- the invention offers possibility of using CD4 as a component of an anti-HIV agent i reduced and therefore safer and more economical amount than previously been feasible.
- the agent according to the invention may also contain less t the normally effective dose of the polyanionic compound. This advantageous because many of the known polyanionic anti- agents are significantly toxic. For example, sulphat polysaccharides have anti-coagulant activity. When t polyanionic anti-HIV agent is a sulphated polysaccharide, it m be present in the compositions of the invention in an amou which is less than that which would be required in an anti-H agent containing only the sulphated polysaccharide.
- compositions of the invention which conta sulphated polysaccharides may have a lower level of ant coagulant activity attributable to the sulphated polysacchari content than those previously known.
- the polyanionic anti-HIV agents used in the present invention a preferably sulphated polysaccharides. They include, for exampl dextran sulphate, pentosan polysulphate, fucoidan, and dextr sulphate. Other sulphated polysaccharides having anti-H activity (see, for example, EP specifications No's 240,098 a 293,826) may also be used.
- the sulphat polysaccharide contains at least one sulphate group p saccharide unit.
- the anti-HIV agent of the invention may administered enterally (including orally) or parenteral (including intravenously).
- administration via t peritoneum may be more effective in that it results in entry at least some of the anti-HIV agent directly into the lymphat system, within which system viral replication may be extensive.
- the invention also provides the use of the agent described abo against HIV-1 and relates viruses, the agent preferably bei administered peritoneally.
- the invention provides a pharmaceutical compositi containing the anti-HIV agent of the invention together with inert carrier or diluent and the agent of the invention for u in the manufacture of a pharmaceutical composition against HIV and related viruses.
- the invention additionally provides a method of treatment of human or animal subject carrying the HIV-1 virus or a rela virus, comprising administering to the subject a pharmaceutica effective amount of the agent of the invention.
- the CD4 or CD4-like material and the polyanionic anti-HIV ag may be administered to a subject one after the other, in order although preferably with the CD4 or CD4-like mater being administered before the polyanionic agent, when u against HIV-1 or a related virus.
- the invention thus provides CD4 or a CD4-like material, of amount less than its usual anti-virally effective dose, and polyanionic anti-HIV agent, for use in a method of treatment of human or animal subject carrying the HIV-1 virus or a relat virus in whic the CD4 or CD4-like material are administered the subject one after the other.
- T dextrin sulphate was produced by sulphation of a dextrin weight average molecular weight of about 20,000 daltons, using sulphur trioxide/trimethylamine complex, the degree substitution being approximately one sulphate group per gluco unit.
- the srCD4 was produced in a baculo virus system and w purchased from American Biotechnology Inc.
- Example 1
- T srCD4/HIV-l was then added to the dextrin sulphate pre-treat M8166 cells, and the plates read at 48 - 72 hours for t presence of syncytia, shown in the table below by +.
- srCD4 inhibited HIV infection of M8166 cells at 6 ug/ml (final concentration).
- dextrin sulphate inhibited HIV-1 infecti of M8166 cells at 5-10 ug/ml.
- 2 - 5.0 ug/ml of dextrin sulphate inhibited HIV-1 infection in t presence of srCD4 at a concentration of 0.05 - 0.09 ug/ml.
- Th represents a 10 ⁇ reduction in the quantity of srCD4 required prevent HIV-1 infection, and shows that the effect of the t drugs together is synergistic rather than simply additive.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Cell Biology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention provides an agent against HIV and related viruses, in dosage unit form, comprising CD4 or a CD4-like material and a polyanionic anti-HIV agent, the content of CD4 or CD4-like material in the agent being less than the anti-virally effective dose of the CD4 or CD4-like material alone. It has been found that when the CD4 or CD4-like material is used together with a polyanionic anti-HIV agent, the combination is more effective against HIV infection than would be the case if the anti-viral effect was simply additive.
Description
PHARMACEUTICALCOMPOSITIONCOMPRISINGCD4ANDAPOLYANIONICANTI- HIVAGENTAND USETHEREOF
This invention relates to pharmaceutically active compositi and to their use as agents against human immunodeficiency vi and related viruses.
The HIV infection cycle includes a number of steps, each of th steps being a possible target for the use of chemotherapy hinder the infection. The first step in the infection cycle the attachment of the HIV virus to the host cell. The m receptor for the virus is believed to be the cell surf glycoprotein, designated CD4, which is present in some lymphocytes and in some macrophages. Much attention therefore been given to identifying agents which are capable blocking attachment of the virus to CD4.
It is believed that the HIV virus attaches itself to CD4 by mea of interaction between CD4 and the surface glycoprotein, gpl2 of the virus. It has been found that soluble recombinant C
(srCD4), made by genetic engineering, can block attachment of H virus to cellular CD4, thereby inhibiting HIV infection in vitr
Therefore, it has appeared that HIV infection might preventable by administration of srCD4. Other CD4-li materials, capable of binding to gpl20, such as CD4-Ig immunoadhesins, CD4 V1-V2 domains, and CD4-derived peptides, ha also been proposed as anti-HIV agents. However, the performan
of CD4 and CD4-like materials in preventing the HIV virus fr binding to cells has until now been disappointing, a much high concentration of the agent being necessary than had been hoped.
Other anti-HIV agents which block attachment of the virus cells are a number of polyanionic compounds which include Eva Blue, aurintricarboxylic acid (ATA), suramin, and certai sulphated polysaccharides. It might have been thought that i CD4 and such polyanionic anti-HIV agents were use simultaneously, the total anti-HIV activity would at best be th sum of their separate activities.
However, we have now found that when CD4 (which is used here an below, except where otherwise indicated, to include both CD4 an CD4-like materials) and a polyanionic anti-HIV agent, such a sulphated polysaccharide, are used together, they are much mor effective against HIV infection than would be the case if th anti-viral effect was simply additive.
Accordingly, the invention provides an agent against HIV an related viruses, in dosage unit form, comprising CD4 or a CD4 like material and a polyanionic anti-HIV agent the content of CD and CD4-like material in the agent being less than the anti virally effective dose of the CD4 or CD4-like material alone.
The agent according to the invention may contain substantiall
less CD4 than the anti-virally effective dosage of CD4 alo i.e. in the absence of a polyanionic anti-HIV agent. reduction in the amount of CD4 required to achieve the same an viral effect as for CD4 alone may be such that less than o tenth (or, in favourable cases, less than one-hundredth) of amount of CD4 is needed. Accordingly, the invention offers possibility of using CD4 as a component of an anti-HIV agent i reduced and therefore safer and more economical amount than previously been feasible.
The agent according to the invention may also contain less t the normally effective dose of the polyanionic compound. This advantageous because many of the known polyanionic anti- agents are significantly toxic. For example, sulphat polysaccharides have anti-coagulant activity. When t polyanionic anti-HIV agent is a sulphated polysaccharide, it m be present in the compositions of the invention in an amou which is less than that which would be required in an anti-H agent containing only the sulphated polysaccharide.
Consequently, the compositions of the invention which conta sulphated polysaccharides may have a lower level of ant coagulant activity attributable to the sulphated polysacchari content than those previously known.
The polyanionic anti-HIV agents used in the present invention a
preferably sulphated polysaccharides. They include, for exampl dextran sulphate, pentosan polysulphate, fucoidan, and dextr sulphate. Other sulphated polysaccharides having anti-H activity (see, for example, EP specifications No's 240,098 a 293,826) may also be used. Preferably, the sulphat polysaccharide contains at least one sulphate group p saccharide unit.
In therapeutic use, the anti-HIV agent of the invention may administered enterally (including orally) or parenteral (including intravenously). However, administration via t peritoneum may be more effective in that it results in entry at least some of the anti-HIV agent directly into the lymphat system, within which system viral replication may be extensive.
The invention also provides the use of the agent described abo against HIV-1 and relates viruses, the agent preferably bei administered peritoneally.
Further, the invention provides a pharmaceutical compositi containing the anti-HIV agent of the invention together with inert carrier or diluent and the agent of the invention for u in the manufacture of a pharmaceutical composition against HIV and related viruses.
The invention additionally provides a method of treatment of
human or animal subject carrying the HIV-1 virus or a rela virus, comprising administering to the subject a pharmaceutica effective amount of the agent of the invention.
The CD4 or CD4-like material and the polyanionic anti-HIV ag may be administered to a subject one after the other, in order although preferably with the CD4 or CD4-like mater being administered before the polyanionic agent, when u against HIV-1 or a related virus.
The invention thus provides CD4 or a CD4-like material, of amount less than its usual anti-virally effective dose, and polyanionic anti-HIV agent, for use in a method of treatment of human or animal subject carrying the HIV-1 virus or a relat virus in whic the CD4 or CD4-like material are administered the subject one after the other.
The following example illustrates the synergistic action dextrin sulphate with soluble recombinant CD4 (srCD4). T dextrin sulphate was produced by sulphation of a dextrin weight average molecular weight of about 20,000 daltons, using sulphur trioxide/trimethylamine complex, the degree substitution being approximately one sulphate group per gluco unit. The srCD4 was produced in a baculo virus system and w purchased from American Biotechnology Inc.
Example 1
In a duplicated experiment, 2-fold dilutions of solub recombinant CD4, to yield final concentrations of 6 ug/ml down 0.02 ug/ml, were incubated with 2.5 x 103 TCID (tissue cultu infection dose) of HIV-1 virus supernatant (HTLV-IIIb strai Gallo, 1984) at 37°C for 1 hour. 2-fold dilutions of dextr sulphate to yield final concentrations from 10 ug/ml down 0.625 ug/ml were then added to the T-cell line, M8166, at density of 2.5 x 105/ml and incubated at 37°C for 1 hour. T srCD4/HIV-l was then added to the dextrin sulphate pre-treat M8166 cells, and the plates read at 48 - 72 hours for t presence of syncytia, shown in the table below by +.
In the absence of dextrin sulphate, srCD4 inhibited HIV infection of M8166 cells at 6 ug/ml (final concentration). the absence of srCD4, dextrin sulphate inhibited HIV-1 infecti of M8166 cells at 5-10 ug/ml. When both drugs were present, 2 - 5.0 ug/ml of dextrin sulphate inhibited HIV-1 infection in t presence of srCD4 at a concentration of 0.05 - 0.09 ug/ml. Th represents a 10^ reduction in the quantity of srCD4 required prevent HIV-1 infection, and shows that the effect of the t drugs together is synergistic rather than simply additive.
FIRST EXPERIMENT
Dextrin srCD4 (ug/ml)
Sulphate
(ug/ml)
1.5 0.75 0.375 0.18 0.09 0.05 0.
5
2.5
1.25 + +
0.625 + +
0
SECOND EXPERIMENT
Dextrin srCD4 (ug/ml)
Sulphate
(ug/ml)
1.5 0.75 0.375 0.18 0.09 0.05 0.
10
+
+ + +
+ + + + + + + + + + + + + + + + + + + + + + + + + +
METHOD srCD4 diluted into 96 well tray. Add 2.5 x 103 TCID Illb. Incubate at 37oC for 1 hour.
B Dextrin sulphate diluted into another well tray. Add M8166 (2.5 x 105/ml). Incubate at 37°C for 1 hour.
Then add A to B.
Read at 2 - 3 days when positive controls show >95% syncytia.
Claims
1. An agent against HIV and related viruses, in dosage u form, comprising CD4 or a CD4-like material and polyanionic anti-HIV agent, the content of CD4 or CD4-l material in the agent being less than the anti-vira effective dose of the CD4 or CD4-like material alone.
2. The agent of Claim 1 wherein the content of CD4 or CD4-l material is less than one-tenth of the anti-vira effective dose of the Cd4 or CD4-like material alone.
3. The agent of Claim 1 wherein the content of CD4 or CD4-li material is less than one-hundredth of the anti-viral effective dose of the Cd4 or CD4-like material alone.
4. The agent of any of Claims 1 to 3 wherein the content said polyanionic anti-HIV agent is less than the ant virally effective dose of the polyanionic anti-HIV age alone.
5. The agent of any of Claims 1 to 4 wherein said polyanion anti-HIV agent is a sulphated polysaccharide.
6. The agent of Claim 5 wherein the sulphated polysaccharide dextrin sulphate.
7. The agent of Claim 5 or 6 wherein said sulphat polysaccharide contains at least one sulphate group p saccharide unit.
8. The use of an agent according to any preceding claim again HIV-1 and related viruses.
9. The use of an agent, as claimed in Claim 8, wherein t agent is administered peritoneally.
10. The agent of any of Claims 1 to 7, adapted f intraperitoneal administration.
11. The agent of any of Claims 1 to 7, for use in t manufacture of a pharmaceutical composition against HIV and related viruses.
12. A pharmaceutical composition containing the agent of any Claims 1 to 7 and an inert carrier or diluent.
13. A method of treatment of a human or animal subject carryi the HIV-1 virus or a related virus, comprising administeri to the subject a pharmaceutically effective amount of t agent of any of Claims 1 to 7.
14. CD4 or CD4-like material, of an amount less than its us anti-virally effective dose, and a polyanionic anti- agent, for use in a method of treatment of a human or ani subject carrying the HIV-1 virus or a related virus in wh the CD4 or CD4-like material and the polyanionic agent administered to the subject one after the other, in order.
15. A method of treatment of a human or animal subject carryi the HIV-1 virus or a related virus, comprising administeri to the subject, one after the other but in any order, CD4 a CD4-like material, of an amount less than its usual ant virally effective dose, and a polyanionic anti-HIV agent.
16. A method according to Claim 15, wherein the CD4 or CD4-li material is administered before the polyanionic anti-H agent.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3515281A JPH06502846A (en) | 1990-09-25 | 1991-09-23 | Pharmaceutical composition comprising CD4 and anti-HIV polyanion agent and method for using the same |
| AU86127/91A AU653962B2 (en) | 1990-09-25 | 1991-09-23 | Pharmaceutical composition comprising CD4 and a polyanionic anti-HIV agent and use thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9020872.9 | 1990-09-25 | ||
| GB909020872A GB9020872D0 (en) | 1990-09-25 | 1990-09-25 | Pharmaceutical compositions and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992004909A1 true WO1992004909A1 (en) | 1992-04-02 |
Family
ID=10682731
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1991/001627 WO1992004909A1 (en) | 1990-09-25 | 1991-09-23 | Pharmaceutical composition comprising cd4 and a polyanionic anti-hiv agent and use thereof |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0550529A1 (en) |
| JP (1) | JPH06502846A (en) |
| AU (1) | AU653962B2 (en) |
| CA (1) | CA2092093A1 (en) |
| GB (1) | GB9020872D0 (en) |
| IE (1) | IE913341A1 (en) |
| NZ (1) | NZ239909A (en) |
| PT (1) | PT99058B (en) |
| WO (1) | WO1992004909A1 (en) |
| ZA (1) | ZA917596B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993021943A1 (en) * | 1992-05-07 | 1993-11-11 | M.L. Laboratories Plc | Antiviral agent comprising cd4 and an h2 histone |
| US5272261A (en) * | 1989-01-11 | 1993-12-21 | Merrell Dow Pharmaceuticals Inc. | Preparation of sulfated polysaccharide fractions |
| FR2838649A1 (en) * | 2002-04-19 | 2003-10-24 | Commissariat Energie Atomique | ANTI-HIV COMPOSITION, METHOD OF MANUFACTURE AND MEDICINAL PRODUCT |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0293826A2 (en) * | 1987-06-02 | 1988-12-07 | Stichting REGA V.Z.W. | Therapeutic and prophylactic application of sulfated polysaccharides against AIDS |
| EP0332952A2 (en) * | 1988-03-12 | 1989-09-20 | BASF Aktiengesellschaft | Polysulfated heparin combinations against retrovirus infections |
| WO1989011860A1 (en) * | 1988-06-10 | 1989-12-14 | Biogen, Inc. | Combinations of soluble t4 proteins and anti-retroviral agents and methods for treating or preventing aids, arc and hiv infection |
| WO1990000596A1 (en) * | 1988-07-07 | 1990-01-25 | The Trustees Of The University Of Pennsylvania | Method of modulating virus-host cell interactions using carbohydrates and carbohydrate derivatives |
-
1990
- 1990-09-25 GB GB909020872A patent/GB9020872D0/en active Pending
-
1991
- 1991-09-23 NZ NZ239909A patent/NZ239909A/en unknown
- 1991-09-23 JP JP3515281A patent/JPH06502846A/en active Pending
- 1991-09-23 EP EP91916829A patent/EP0550529A1/en not_active Withdrawn
- 1991-09-23 WO PCT/GB1991/001627 patent/WO1992004909A1/en not_active Application Discontinuation
- 1991-09-23 AU AU86127/91A patent/AU653962B2/en not_active Ceased
- 1991-09-23 CA CA002092093A patent/CA2092093A1/en not_active Abandoned
- 1991-09-24 IE IE334191A patent/IE913341A1/en not_active Application Discontinuation
- 1991-09-24 ZA ZA917596A patent/ZA917596B/en unknown
- 1991-09-25 PT PT99058A patent/PT99058B/en not_active IP Right Cessation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0293826A2 (en) * | 1987-06-02 | 1988-12-07 | Stichting REGA V.Z.W. | Therapeutic and prophylactic application of sulfated polysaccharides against AIDS |
| EP0332952A2 (en) * | 1988-03-12 | 1989-09-20 | BASF Aktiengesellschaft | Polysulfated heparin combinations against retrovirus infections |
| WO1989011860A1 (en) * | 1988-06-10 | 1989-12-14 | Biogen, Inc. | Combinations of soluble t4 proteins and anti-retroviral agents and methods for treating or preventing aids, arc and hiv infection |
| WO1990000596A1 (en) * | 1988-07-07 | 1990-01-25 | The Trustees Of The University Of Pennsylvania | Method of modulating virus-host cell interactions using carbohydrates and carbohydrate derivatives |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5272261A (en) * | 1989-01-11 | 1993-12-21 | Merrell Dow Pharmaceuticals Inc. | Preparation of sulfated polysaccharide fractions |
| US5861383A (en) * | 1989-01-11 | 1999-01-19 | Merrell Pharmaceuticals Inc. | Sulfated polysaccharide fractions having anti-HIV activity |
| WO1993021943A1 (en) * | 1992-05-07 | 1993-11-11 | M.L. Laboratories Plc | Antiviral agent comprising cd4 and an h2 histone |
| FR2838649A1 (en) * | 2002-04-19 | 2003-10-24 | Commissariat Energie Atomique | ANTI-HIV COMPOSITION, METHOD OF MANUFACTURE AND MEDICINAL PRODUCT |
| WO2003089000A3 (en) * | 2002-04-19 | 2004-04-08 | Commissariat Energie Atomique | Anti-hiv composition, production method thereof and medicament |
| US7494975B2 (en) | 2002-04-19 | 2009-02-24 | Commissariat A L'energie Atomique | Anti-HIV composition, production method thereof and medicament |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2092093A1 (en) | 1992-03-26 |
| AU653962B2 (en) | 1994-10-20 |
| JPH06502846A (en) | 1994-03-31 |
| EP0550529A1 (en) | 1993-07-14 |
| IE913341A1 (en) | 1992-02-25 |
| PT99058A (en) | 1992-08-31 |
| PT99058B (en) | 1999-02-26 |
| NZ239909A (en) | 1993-02-25 |
| ZA917596B (en) | 1992-05-27 |
| AU8612791A (en) | 1992-04-15 |
| GB9020872D0 (en) | 1990-11-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Baba et al. | Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro. | |
| CA2072573C (en) | Treatment of human retroviral infections with 2',3'-dideoxyinosine | |
| Andrieu et al. | Effects of cyclosporin on T-cell subsets in human immunodeficiency virus disease | |
| KR960013435B1 (en) | Therapeutic composition for the treatment of virus infection and hiv infection comprising viral inhibitor and dsrna | |
| JPS6084224A (en) | Medicinal composition | |
| CN113573732A (en) | TACI-Fc fusion protein and application thereof | |
| IE881894L (en) | Double-stranded rna correction of abnormalities in¹circulating immune complexes and monocyte function | |
| AU653962B2 (en) | Pharmaceutical composition comprising CD4 and a polyanionic anti-HIV agent and use thereof | |
| US5714462A (en) | Antiviral agent comprising CD4 and H2 histone | |
| PT99057B (en) | A PROCESS FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS CONTAINING A SYNERGIC MIXTURE OF GLYCOPROTEIN CD4 FROM THE SURFACE OF THE ECELULAS OR AN ANALYTICAL COMPONENT WITH AN ANTI-HIV POLYURIC AGENT, PARTICULARLY A SULPHATE POLYSSACRATE | |
| Olson et al. | Ribosomal inhibitory proteins from plants inhibit HIV-1 replication in acutely infected peripheral blood mononuclear cells | |
| EP0666755B1 (en) | Inhibition of hiv-infection | |
| US6869925B1 (en) | Inhibition of retrovirus infection | |
| Zeidner et al. | Treatment of FeLV-induced immunodeficiency syndrome (FeLV-FAIDS) with controlled release capsular implantation of 2′, 3′-dideoxycytidine | |
| Acosta et al. | Agents for treating human immunodeficiency virus infection | |
| KR100227095B1 (en) | Anti-hiv agent | |
| Polsky | Antiviral chemotherapy for infection with human immunodeficiency virus | |
| EP1194158B1 (en) | The use of the protein uk 114 for inhibiting organ transplant rejection | |
| Ohara | Immunosuppression in solid organ transplantation: A nutrition perspective | |
| EP0765662B1 (en) | Use of 5,6-o-benzylidene-l-ascorbic acid or salts thereof for the manufacture of a medicament for the treatment of hiv | |
| US7368423B1 (en) | Composition and method for treating chronic allograft rejection | |
| Flechner et al. | Cyclosporine and prednisone immunosuppression in pediatric recipients of renal allografts | |
| WO1993011763A1 (en) | Use of cytochalasins for inhibiting viral replication | |
| KR20050094461A (en) | A therapeutic composition for the treatment of hiv-1 and hiv-2 | |
| AU743942B2 (en) | Mixtures of at least two reverse transcriptase inhibitors and hydroxycarbamide, in particular for inhibiting retroviral spread |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AT AU BB BG BR CA CH CS DE DK ES FI GB HU JP KP KR LK LU MC MG MN MW NL NO PL RO SD SE SU US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE BF BJ CF CG CH CI CM DE DK ES FR GA GB GN GR IT LU ML MR NL SE SN TD TG |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2092093 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1991916829 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 1991916829 Country of ref document: EP |
|
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 1991916829 Country of ref document: EP |