WO1996041641A1 - Pharmaceutical compositions with analgesic activity - Google Patents
Pharmaceutical compositions with analgesic activity Download PDFInfo
- Publication number
- WO1996041641A1 WO1996041641A1 PCT/EP1996/002472 EP9602472W WO9641641A1 WO 1996041641 A1 WO1996041641 A1 WO 1996041641A1 EP 9602472 W EP9602472 W EP 9602472W WO 9641641 A1 WO9641641 A1 WO 9641641A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- analgesic activity
- pharmaceutical compositions
- perchloric acid
- extracting
- liver
- Prior art date
Links
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229920001184 polypeptide Polymers 0.000 claims abstract description 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 8
- 210000004185 liver Anatomy 0.000 claims abstract description 6
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 241000124008 Mammalia Species 0.000 claims abstract description 3
- 241000283707 Capra Species 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims 1
- 241000700159 Rattus Species 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 2
- 235000004252 protein component Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940040511 liver extract Drugs 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000007619 statistical method Methods 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
Definitions
- the present invention relates to pharmaceutical formulations with analgesic activity containing as active ingredient polypeptides obtainable by extraction of mammal liver, particularly goat liver, with perchloric acid.
- polypeptides which can be used according to the invention are disclosed in EP 574 394 as potent antineoplastic agents.
- EP 574 394 the effectiveness of said polypeptides in controlling tumor-related pain is described.
- compositions of the invention will preferably contain the goat liver extract defined in EP 574 394 with the abbreviation L6E, essentially consisting of three main protein components with molecular weights of 50,000, 14,000 and 10,000 daltons in SDS-PA6E, or the single protein components with molecular weights of 50,000 and/or 14,000 and/or 10,000.
- compositions will be preferably administered by the parenteral route, for example intramuscularly or subcutaneously, in the form of sterile solutions or suspensions.
- parenteral route for example intramuscularly or subcutaneously
- examples of said formulations comprise vials or ampoules containing the freeze-dried ingredient to be dissolved before use with physiological sterile solutions, solutions or suspensions in sterile aqueous or oily solvents suitable to the in vivo administration.
- the daily dosage, related to the LGE extract will typically range from 0.1 to 20 mg of extract (or the equivalent of the components thereof) .
- the central analgesic activity is particularly fast and it is not accompanied by tolerance and/or addiction phenomena.
- Analgesic thresholds were evaluated using the hot plate test (56*C). LGE was administered subcutaneously to normal Sprague Dawley rats (Charles River, Calco, CO) at the doses reported in the table.
- the hot plate test evidences a "central" analgesic effect.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Marine Sciences & Fisheries (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Pharmaceutical compositions with analgesic activity, containing as the active ingredient polypeptides obtainable by extracting mammal liver with perchloric acid.
Description
PHARMACEUTICAL COMPOSITIONS WITH ANALGESIC ACTIVITY
The present invention relates to pharmaceutical formulations with analgesic activity containing as active ingredient polypeptides obtainable by extraction of mammal liver, particularly goat liver, with perchloric acid.
The polypeptides which can be used according to the invention are disclosed in EP 574 394 as potent antineoplastic agents. In the same Patent EP 574 394, the effectiveness of said polypeptides in controlling tumor-related pain is described.
Now it has been found that said polypeptides have a potent central analgesic activity and are therefore capable of controlling pain of various etiology and not only that tumour-related. The compositions of the invention will preferably contain the goat liver extract defined in EP 574 394 with the abbreviation L6E, essentially consisting of three main protein components with molecular weights of 50,000, 14,000 and 10,000 daltons in SDS-PA6E, or the single protein components with molecular weights of 50,000 and/or 14,000 and/or 10,000.
The compositions will be preferably administered by the parenteral route, for example intramuscularly or subcutaneously, in the form of sterile solutions or suspensions. Examples of said formulations comprise vials or ampoules containing the freeze-dried ingredient to be dissolved before use with physiological sterile solutions, solutions or suspensions in sterile aqueous or oily solvents suitable to the in vivo administration.
The daily dosage, related to the LGE extract, will typically range from 0.1 to 20 mg of extract (or the equivalent of the components thereof) .
The central analgesic activity, evidenced on the basis of the pharmacological tests reported hereinbelow, is particularly fast and it is not accompanied by tolerance and/or addiction phenomena.
EXAMPLE
Analgesic thresholds were evaluated using the hot plate test (56*C). LGE was administered subcutaneously to normal Sprague Dawley rats (Charles River, Calco, CO) at the doses reported in the table.
Statistical analysis was carried out by means of the variance analysis, followed by the Dunnet's test for multiple comparisons.
Treatment Basal 30 min. 60 min. 120 min. 240 min. 24 hours
Controls 9.3 ± 0.4* 9.6 ± 0.5 9.6 ± 0.4 9.0 ± 0.4 9.3 ± 0.4 10 ± 0.6 (physiologi¬ cal solution)
LGE20 9.2 ± 0.4 11.1 ± 0.6 10.9 1 0.8 10.2 1 0.4 9.0 ± 0.6 10.7 1 0.5 μg/rat >
LGE40 9.8 ± 0.3 11.3 ± 0.4 12 ± 0.6 9.7 ± 0.4 9.5 ± 0.5 10.9 ± 0.7 μg/rat
LGE80 9.3 ± 0.4 11.1 ± 0.8 11 ± 0.5 9.9 ± 0.4 10.3 ± 0.5 10.6 ± 0.6 μg/rat
LGE160 9.8 ± 0.4 12.7 ± 0.5 12.9 ± 0.5 10.7 ± 0.4 10.7 ± 0.3 10.2 ± 0.6 μg/rat
* = mean ± standard error of 8 animals
A significant increase in the analgesia threshold is observed compared with the basal values at times 30 and 60 minutes for higher dosages, with a dose/response effect not elucidated.
The hot plate test evidences a "central" analgesic effect.
Claims
1. Pharmaceutical compositions with analgesic activity containing as the active ingredient one or more of the polypeptides obtainable by extracting mammal liver with perchloric acid.
2. Compositions according to claim 1, containing as the active ingredient one or more of the polypeptides obtainable by extracting goat liver with perchloric acid.
3. The use of the polypeptides obtainable by extracting goat liver with perchloric acid, for the preparation of a medicament with analgesic activity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU62234/96A AU6223496A (en) | 1995-06-13 | 1996-06-07 | Pharmaceutical compositions with analgesic activity |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT95MI001253A IT1276707B1 (en) | 1995-06-13 | 1995-06-13 | PHARMACEUTICAL COMPOSITIONS WITH ANALGESIC ACTIVITY |
| ITMI95A001253 | 1995-06-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996041641A1 true WO1996041641A1 (en) | 1996-12-27 |
Family
ID=11371805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1996/002472 WO1996041641A1 (en) | 1995-06-13 | 1996-06-07 | Pharmaceutical compositions with analgesic activity |
Country Status (4)
| Country | Link |
|---|---|
| AU (1) | AU6223496A (en) |
| IT (1) | IT1276707B1 (en) |
| WO (1) | WO1996041641A1 (en) |
| ZA (1) | ZA964954B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992010197A1 (en) * | 1990-12-11 | 1992-06-25 | Zetesis S.P.A. | Substances of polypeptide nature useful in human therapy |
| WO1996002567A1 (en) * | 1994-07-14 | 1996-02-01 | Zetesis S.P.A. | Proteins from mammalian liver and their use in oncology |
-
1995
- 1995-06-13 IT IT95MI001253A patent/IT1276707B1/en active IP Right Grant
-
1996
- 1996-06-07 AU AU62234/96A patent/AU6223496A/en not_active Abandoned
- 1996-06-07 WO PCT/EP1996/002472 patent/WO1996041641A1/en active Application Filing
- 1996-06-11 ZA ZA964954A patent/ZA964954B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992010197A1 (en) * | 1990-12-11 | 1992-06-25 | Zetesis S.P.A. | Substances of polypeptide nature useful in human therapy |
| WO1996002567A1 (en) * | 1994-07-14 | 1996-02-01 | Zetesis S.P.A. | Proteins from mammalian liver and their use in oncology |
Also Published As
| Publication number | Publication date |
|---|---|
| IT1276707B1 (en) | 1997-11-03 |
| ITMI951253A0 (en) | 1995-06-13 |
| ZA964954B (en) | 1997-01-23 |
| AU6223496A (en) | 1997-01-09 |
| ITMI951253A1 (en) | 1996-12-13 |
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