EP0790828A1 - Verwendung von phosphonoessig oder-ameisesäuren gegen human herpes virus-7 (hhv-7) - Google Patents
Verwendung von phosphonoessig oder-ameisesäuren gegen human herpes virus-7 (hhv-7)Info
- Publication number
- EP0790828A1 EP0790828A1 EP95937066A EP95937066A EP0790828A1 EP 0790828 A1 EP0790828 A1 EP 0790828A1 EP 95937066 A EP95937066 A EP 95937066A EP 95937066 A EP95937066 A EP 95937066A EP 0790828 A1 EP0790828 A1 EP 0790828A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- hhv
- treatment
- infection
- phosphonoacetic
- activity against
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 241000701041 Human betaherpesvirus 7 Species 0.000 title description 12
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 241001529453 unidentified herpesvirus Species 0.000 claims abstract description 10
- 208000037773 HHV-7 infectious disease Diseases 0.000 claims abstract description 8
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims abstract description 8
- 230000000694 effects Effects 0.000 claims abstract description 7
- 238000011321 prophylaxis Methods 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 15
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 10
- XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- 229960005102 foscarnet Drugs 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 241000282412 Homo Species 0.000 claims description 3
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000003981 vehicle Substances 0.000 description 6
- 210000004700 fetal blood Anatomy 0.000 description 5
- 241000700605 Viruses Species 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 208000015181 infectious disease Diseases 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
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-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
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 241000701027 Human herpesvirus 6 Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002391 anti-complement effect Effects 0.000 description 1
- 108010008730 anticomplement Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000012530 fluid 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
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
-
- 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
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Definitions
- This invention relates to treatment of infection caused by human herpesvirus 7 (HHV-7), and to the use of compounds in the preparation of a medicament for use in the treatment of such conditions.
- HHV-7 human herpesvirus 7
- Phosphonoacetic Acid PAA
- PFA phosphonoformic acid
- PFA foscarnet
- PHA Phosphonoacetic Acid
- PFA phosphonoformic acid
- HHV-7 Human herpesvirus 7 (HHV-7) is a recently discovered member of the family Herpesviridae. The virus was first isolated in 1989 from the peripheral blood lymphocytes (PBL) of a healthy individual that were being cultured under conditions that lead to T-cell activation.
- PBL peripheral blood lymphocytes
- HHV-7 has been isolated from the saliva of as many as 75% of healthy adults. Antibodies to HHV-7 can be detected in serum specimens from approximately 90% of the normal population and seroconversion usually occurs during childhood after the age of 2. It is possible that HHV-7 may play a role in the activation of human immunodeficiency virus (HIV-1).
- the present invention provides a method of treatment of HHV-7 infection in humans, which method comprises the administration to the human in need of such treatment, an effective amount of a pyrophosphate analogue having activity against herpesviruses.
- the compound may be administered in the form of a bioprecursor or pharmaceutically acceptable salt.
- fluid unit dose forms are prepared containing the compound and a sterile vehicle.
- the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
- Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
- adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
- the composition can be frozen after filling into the vial and the water removed under vacuum.
- Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
- a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
- the compound may be administered by the oral route to humans and may be compounded in the form of syrup, tablets or capsule.
- any pharmaceutical carrier suitable for formulating such solid compositions may be used, for example magnesium stearate, starch, lactose, glucose, rice, flour and chalk.
- the compound may also be in the form of an ingestible capsule, for example of gelatin, to contain the compound, or in the form of a syrup, a solution or a suspension.
- Suitable liquid pharmaceutical carriers include ethyl alcohol, glycerine, saline and water to which flavouring or colouring agents may be added to form syrups.
- compositions will usually be accompanied by written or printed directions for use in the medical treatment concerned.
- An amount effective to treat the virus infection depends on the nature and severity of the infection and the weight of the mammal.
- a suitable dosage unit might contain from 50mg to lg of active ingredient, for example 100 to 500mg. Such doses may be administered 1 to 4 times a day or more usually 2 or 3 times a day.
- the effective dose of compound will, in general, be in the range of from 0.2 to 40mg per kilogram of body weight per day.
- the usual dosage for foscarnet in treatment of cytomegalovirus infections are as indicated on the British product data sheet, beginning with a 30 minute infusion of 20 mg/kg body weight.
- the present invention also provides the use of a pyrophosphate analogue having activity against herpesviruses in the preparation of a medicament for use in the treatment of HHV-7 infection. Such treatment may be carried out in the manner as hereinbefore described.
- the present invention further provides a pharmaceutical composition for use in the treatment of HHV-7 infection, which comprises an effective amount of a pyrophosphate analogue having activity against herpesviruses, and a pharmaceutically acceptable carrier.
- a pharmaceutical composition for use in the treatment of HHV-7 infection which comprises an effective amount of a pyrophosphate analogue having activity against herpesviruses, and a pharmaceutically acceptable carrier.
- Such compositions may be prepared in the manner as hereinafter described.
- Human mononuclear cells were isolated from umbilical cord blood and inoculated in triplicate with the test virus. One hour later, duplicate dilutions of the compound were added, resulting in 0, 5, 10, 50, or 100 ⁇ M final concentrations. After 3 - 6 days, cellls were removed and tested for the presence of virus by indirect immunofluorescence (IFA) using type specific monoclonal antibodies. Three fields of 100 cells each were read from each sample.
- IFA indirect immunofluorescence
- a Dilutions of the compounds were added 1 hr after viral inoculation of human cord blood.
- the % infected cells was measured by anti-complement immunofluorescence (ACIF).
- ACIF anti-complement immunofluorescence
- AU numbers are averages of results of cord blood from 3 donors and triplicate readings were performed on each sample. Each reading represents actual counting of 3 fields.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9422781 | 1994-11-11 | ||
| GB9422781A GB9422781D0 (en) | 1994-11-11 | 1994-11-11 | Pharmaceuticals |
| PCT/EP1995/004445 WO1996014847A1 (en) | 1994-11-11 | 1995-11-10 | Use of phosphonoacetic or-formic acids against human herpes virus -7 (hhv-7) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0790828A1 true EP0790828A1 (de) | 1997-08-27 |
Family
ID=10764242
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP95937066A Withdrawn EP0790828A1 (de) | 1994-11-11 | 1995-11-10 | Verwendung von phosphonoessig oder-ameisesäuren gegen human herpes virus-7 (hhv-7) |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0790828A1 (de) |
| JP (1) | JPH10509704A (de) |
| GB (1) | GB9422781D0 (de) |
| WO (1) | WO1996014847A1 (de) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2177788C2 (ru) * | 1998-06-10 | 2002-01-10 | Данилов Леонид Леонидович | Средство для профилактики и лечения инфекционных заболеваний и коррекции патологических состояний живого организма |
| RU2542420C1 (ru) * | 2014-03-13 | 2015-02-20 | Общество С Ограниченной Ответственностью "Гамаветфарм" | Лекарственное средство на основе полипренилфосфатов и бета-ситостерина и способ его получения |
-
1994
- 1994-11-11 GB GB9422781A patent/GB9422781D0/en active Pending
-
1995
- 1995-11-10 EP EP95937066A patent/EP0790828A1/de not_active Withdrawn
- 1995-11-10 JP JP8515727A patent/JPH10509704A/ja active Pending
- 1995-11-10 WO PCT/EP1995/004445 patent/WO1996014847A1/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9614847A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1996014847A1 (en) | 1996-05-23 |
| JPH10509704A (ja) | 1998-09-22 |
| GB9422781D0 (en) | 1995-01-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19970506 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): BE CH DE FR GB IT LI NL |
|
| RBV | Designated contracting states (corrected) |
Designated state(s): BE CH DE FR GB IT LI NL |
|
| 17Q | First examination report despatched |
Effective date: 20010307 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 20010918 |