CA1171421A - Lysine salts having analgesic activity - Google Patents
Lysine salts having analgesic activityInfo
- Publication number
- CA1171421A CA1171421A CA000403645A CA403645A CA1171421A CA 1171421 A CA1171421 A CA 1171421A CA 000403645 A CA000403645 A CA 000403645A CA 403645 A CA403645 A CA 403645A CA 1171421 A CA1171421 A CA 1171421A
- Authority
- CA
- Canada
- Prior art keywords
- lysine
- pyrrole
- chlorobenzoyl
- acetic acid
- salt
- 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.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
- G01S3/00—Direction-finders for determining the direction from which infrasonic, sonic, ultrasonic, or electromagnetic waves, or particle emission, not having a directional significance, are being received
- G01S3/78—Direction-finders for determining the direction from which infrasonic, sonic, ultrasonic, or electromagnetic waves, or particle emission, not having a directional significance, are being received using electromagnetic waves other than radio waves
- G01S3/782—Systems for determining direction or deviation from predetermined direction
- G01S3/783—Systems for determining direction or deviation from predetermined direction using amplitude comparison of signals derived from static detectors or detector systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Physics & Mathematics (AREA)
- Electromagnetism (AREA)
- Remote Sensing (AREA)
- Radar, Positioning & Navigation (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Photometry And Measurement Of Optical Pulse Characteristics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
ABSTRACT
Novel lysine salts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid, having the following structural formula:
are prepared by reacting equimolecular amounts of 5-(p-chlorobenzoyl)-1,4-dimethy~-pyrrole-2-acetic acid and lysine in an aqueous or hydroalcoholic medium, at a temperature between 0 and 100°C, and isolating the salt thus obtained~
The lysine used may be either L-lysine or DL-lysine. The compounds of the invention have analgesic activity and may be used in human therapy for the treatment of acute or chronic pain arising from malignant neoplasms, oral or orthopedic surgery, osteoarthritis and headaches of various origins.
Novel lysine salts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid, having the following structural formula:
are prepared by reacting equimolecular amounts of 5-(p-chlorobenzoyl)-1,4-dimethy~-pyrrole-2-acetic acid and lysine in an aqueous or hydroalcoholic medium, at a temperature between 0 and 100°C, and isolating the salt thus obtained~
The lysine used may be either L-lysine or DL-lysine. The compounds of the invention have analgesic activity and may be used in human therapy for the treatment of acute or chronic pain arising from malignant neoplasms, oral or orthopedic surgery, osteoarthritis and headaches of various origins.
Description
The present invention relates to new lysine salts having analgesic activity and to a process for the prepaxation thereof.
More particularly, the new compounds with which the invention is concerned are salts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid (I) with the basic amino acid lysine (II), having the structural formula (A):
Cl ~ 3~ ~ -CH2COOH . H2N_(cH2)4_1H_cOOH (A) (I) (II) The lysine may be used as L-lysine or as DL-lysine. Thus, the basic component of the formula (II) above can represent either L-lysine or DL-lysine.
The salt obtained with L-lysine wil`l be referred to hereinafter as L-(A), whereas that obtained with DL-lysine will be referred to as DL-(A). The compounds according to the invention have more than satisfactory analgesic activity, as indicated by the phenyl-quinone "writhing test". In the test carried out, no substantial difference was observed between the results obtained with L-(A) and DL-(A)o Acute toxicity of L-(A) and DL-(A) in mice and rats was also comparable.
The salts of the formula (A) are prepared in accordance with the invention by reacting equimolecular amounts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid and lysine in an aqueous or hydroalcoholic medium, at a ~-~7 ~
temperature of between 0 and 100C, and isolating the salt thus obtained.
The salt may be isolated in conventional manner, for example, by concentrating or cooling the reaction medium or by treating it with a non-solvent.
The solubility of the compounds according to the invention in water which is much higher than that of the salts of the acid component (I) with inorganic cations and the pH of the aqueous solutions thereof which is quite near neutrality permit the formulation of preparations for parenteral use.
Thus, the compounds of the present invention may be used in human therapy for the treatment of acute or chronic pain arising from malignant neoplasms, oral surgery, osteoarthritis, headaches of various origins, and general or orthopedic surgery. The method of administration pro-posed is oral, parenteral or rectal. Tablets, pills or capsules containing between 50 and 800 mg of the salt of formula (A) are proposed for oral use, the recommended dosage being 1-6 per 24 hours.
Prepared solutions or vials containing the salt of formula (A) in liophylized form, with a vial of solvent-carrier, are proposed for parenteral use, the amount of salt (A) in each vial being between 50 and 500 mg. The recommended dosage is 1-3 vials per 24 hours.
Suppositories containing between 100 and 1000 mg of the salt of formula (A) are proposed for rectal use, the recommended dosage being 1-5 suppositories per 24 hours.
The analgesic effect of the salt of formula (A) was studied with the phenyl-quinone writhing test, as described by Hendershot & Forsaith in J. Phartnacol. Exp.
Therap. 123, 237 (1959). Male Coss CD-l mice, fasting for 3 hours, were treated orally with the salt (A) 30 minutes prior to endoperitoneal injection of 0.25 mg of a 0.02%
solution of phenyl-quinone in 5 : 95 ethanol and water.
From the fifth minute after injection of the phenyl-quinone, the abdominal spasms (writhing3 were counted in each animal over a period of 15 minutes. Groups of 10 animals were used for each dose tested. The analgesic effect of the salt, expressed as DE50 (the dosage which reduced the numher of abdominal contractions by 50% as compared with untreated animals) was 0.72 mg/kg in the case of L-(A) and 0~77 mg/kg in the case of DL-(A). In the case of bo-th compounds, the oral DL50 was in excess of 1 g/kg for both mice and rats.
The remarkable analgesic activity noted above of the two compounds is accompanied by complete lack of ulcerative activity. Male COBS CD (SD) rats, weighing between 160 and 200 g, fasting since the previous evening, were subjected to slight anaesthesia with ether to permit ligature of the pilorus.
Drinking water was given after the operation.
Two hours later, the rats were given L-(A), DL-(A3, the sodium salt of the acid of formula (I), and ASPIRIN (trademark) orally, in equimolecular doses suspended in 5% gurn arabic.
One hour later, the rats were sacrificed and their stomachs were examined for the presence of ulcers. A
determination was made of the number of rats exhibiting ulcers and the average numbers of ulcers per rat. The following results were obtained.
% Rats with No~ of Ulcers Ulcers per Rat . . _ ~ . _ . _ 121 mg/kg of orally administered L-(A) 0 0 121 mg/kg of orally administered DL-(A) 0 0 97 mg/kg of orally administered sodium s~lt of 5-(p-chlorobenzoyl)--1,4-dimethyl-pyrrole-2-acetic acid 60 14 50 mg/kg of orally administered The following non-limiting examples further illustrate the invention.
Example 1.
29.2 kg of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid are added at intervals, over a l-hour period, to a 50/0 aqueous solution of L-lysine containing 14.6 kg of L-lysine, heated to a temperature of between 40 and 55C and kept under adequate agitation.
The heating and agitation is continued until a clear yellow solution is obtained. The solution is filtered, cooled to ambient temperature, and is slowly stirred while 90 litres of acetone are added. The mass is cooled to between 2 and 5C and is allowed to stand at that temperature for 2 hours, The solution is diluted first with 10 litres of acetone and then with lQ litres of ethyl-ether, and is then filtered. It is dried in a vaccum chamber at a temperature not higher than 40C. It is crystallized from ethanol at 93, followed by filtering and drying in a vaccum chamber at a .
~ ~7~
. ~ .
temperature not higher than 40C. The product obtained is in the form of an ivory-white crystalline powder having a melting point of 218-220C.
In the case of DL-lysine, the DL-(A) has a melting point of 205-207C.
Example 2.
35 kg of distilled water and 10 kg of ethanol are added to a 50% aqueous solution of L-lysine containing 7.3 kg of L-lysine. This solution is heated to a tem-perature between 45 and 50C and 14.6 kg of 5-(p-chloroben-zoyl)-1,4-dimethyl-pyrrole-2-acetic acid are added at intervals, with vigorous stirring. Stirring and heating are continued to dissolution, followed by filtering. The solution obtained is concentrated to dryness in vacuum in a rotary evaporator. The yellowish residue obtained is taken up in 120 kg of absolute ethanol, the mass being sus-pended with violent stirring. Stirring is continued while the product is cooled to 0C. 15 kg of ethyl-ether are added and the product is allowed to stand at 0C for 8 hours. This is followed by filtering and washing with 6 kg of ethyl-ether. Drying is carried out in a vacuum chamber at a temperature not higher than 45C.
More particularly, the new compounds with which the invention is concerned are salts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid (I) with the basic amino acid lysine (II), having the structural formula (A):
Cl ~ 3~ ~ -CH2COOH . H2N_(cH2)4_1H_cOOH (A) (I) (II) The lysine may be used as L-lysine or as DL-lysine. Thus, the basic component of the formula (II) above can represent either L-lysine or DL-lysine.
The salt obtained with L-lysine wil`l be referred to hereinafter as L-(A), whereas that obtained with DL-lysine will be referred to as DL-(A). The compounds according to the invention have more than satisfactory analgesic activity, as indicated by the phenyl-quinone "writhing test". In the test carried out, no substantial difference was observed between the results obtained with L-(A) and DL-(A)o Acute toxicity of L-(A) and DL-(A) in mice and rats was also comparable.
The salts of the formula (A) are prepared in accordance with the invention by reacting equimolecular amounts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid and lysine in an aqueous or hydroalcoholic medium, at a ~-~7 ~
temperature of between 0 and 100C, and isolating the salt thus obtained.
The salt may be isolated in conventional manner, for example, by concentrating or cooling the reaction medium or by treating it with a non-solvent.
The solubility of the compounds according to the invention in water which is much higher than that of the salts of the acid component (I) with inorganic cations and the pH of the aqueous solutions thereof which is quite near neutrality permit the formulation of preparations for parenteral use.
Thus, the compounds of the present invention may be used in human therapy for the treatment of acute or chronic pain arising from malignant neoplasms, oral surgery, osteoarthritis, headaches of various origins, and general or orthopedic surgery. The method of administration pro-posed is oral, parenteral or rectal. Tablets, pills or capsules containing between 50 and 800 mg of the salt of formula (A) are proposed for oral use, the recommended dosage being 1-6 per 24 hours.
Prepared solutions or vials containing the salt of formula (A) in liophylized form, with a vial of solvent-carrier, are proposed for parenteral use, the amount of salt (A) in each vial being between 50 and 500 mg. The recommended dosage is 1-3 vials per 24 hours.
Suppositories containing between 100 and 1000 mg of the salt of formula (A) are proposed for rectal use, the recommended dosage being 1-5 suppositories per 24 hours.
The analgesic effect of the salt of formula (A) was studied with the phenyl-quinone writhing test, as described by Hendershot & Forsaith in J. Phartnacol. Exp.
Therap. 123, 237 (1959). Male Coss CD-l mice, fasting for 3 hours, were treated orally with the salt (A) 30 minutes prior to endoperitoneal injection of 0.25 mg of a 0.02%
solution of phenyl-quinone in 5 : 95 ethanol and water.
From the fifth minute after injection of the phenyl-quinone, the abdominal spasms (writhing3 were counted in each animal over a period of 15 minutes. Groups of 10 animals were used for each dose tested. The analgesic effect of the salt, expressed as DE50 (the dosage which reduced the numher of abdominal contractions by 50% as compared with untreated animals) was 0.72 mg/kg in the case of L-(A) and 0~77 mg/kg in the case of DL-(A). In the case of bo-th compounds, the oral DL50 was in excess of 1 g/kg for both mice and rats.
The remarkable analgesic activity noted above of the two compounds is accompanied by complete lack of ulcerative activity. Male COBS CD (SD) rats, weighing between 160 and 200 g, fasting since the previous evening, were subjected to slight anaesthesia with ether to permit ligature of the pilorus.
Drinking water was given after the operation.
Two hours later, the rats were given L-(A), DL-(A3, the sodium salt of the acid of formula (I), and ASPIRIN (trademark) orally, in equimolecular doses suspended in 5% gurn arabic.
One hour later, the rats were sacrificed and their stomachs were examined for the presence of ulcers. A
determination was made of the number of rats exhibiting ulcers and the average numbers of ulcers per rat. The following results were obtained.
% Rats with No~ of Ulcers Ulcers per Rat . . _ ~ . _ . _ 121 mg/kg of orally administered L-(A) 0 0 121 mg/kg of orally administered DL-(A) 0 0 97 mg/kg of orally administered sodium s~lt of 5-(p-chlorobenzoyl)--1,4-dimethyl-pyrrole-2-acetic acid 60 14 50 mg/kg of orally administered The following non-limiting examples further illustrate the invention.
Example 1.
29.2 kg of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid are added at intervals, over a l-hour period, to a 50/0 aqueous solution of L-lysine containing 14.6 kg of L-lysine, heated to a temperature of between 40 and 55C and kept under adequate agitation.
The heating and agitation is continued until a clear yellow solution is obtained. The solution is filtered, cooled to ambient temperature, and is slowly stirred while 90 litres of acetone are added. The mass is cooled to between 2 and 5C and is allowed to stand at that temperature for 2 hours, The solution is diluted first with 10 litres of acetone and then with lQ litres of ethyl-ether, and is then filtered. It is dried in a vaccum chamber at a temperature not higher than 40C. It is crystallized from ethanol at 93, followed by filtering and drying in a vaccum chamber at a .
~ ~7~
. ~ .
temperature not higher than 40C. The product obtained is in the form of an ivory-white crystalline powder having a melting point of 218-220C.
In the case of DL-lysine, the DL-(A) has a melting point of 205-207C.
Example 2.
35 kg of distilled water and 10 kg of ethanol are added to a 50% aqueous solution of L-lysine containing 7.3 kg of L-lysine. This solution is heated to a tem-perature between 45 and 50C and 14.6 kg of 5-(p-chloroben-zoyl)-1,4-dimethyl-pyrrole-2-acetic acid are added at intervals, with vigorous stirring. Stirring and heating are continued to dissolution, followed by filtering. The solution obtained is concentrated to dryness in vacuum in a rotary evaporator. The yellowish residue obtained is taken up in 120 kg of absolute ethanol, the mass being sus-pended with violent stirring. Stirring is continued while the product is cooled to 0C. 15 kg of ethyl-ether are added and the product is allowed to stand at 0C for 8 hours. This is followed by filtering and washing with 6 kg of ethyl-ether. Drying is carried out in a vacuum chamber at a temperature not higher than 45C.
Claims (8)
1. A process for the preparation of the lysine salts of 5-(p-chlorobenzoyl)-1,4 dimethyl-pyrrole-2-acetic acid, having the following structural formula:
which comprises reacting equimolecular amounts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid and lysine in an aqueous or hydroalcoholic medium, at a temperature between 0 and 100°C, and isolating the salt thus obtained.
which comprises reacting equimolecular amounts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid and lysine in an aqueous or hydroalcoholic medium, at a temperature between 0 and 100°C, and isolating the salt thus obtained.
2. A process according to claim 1, wherein the lysine used is L-lysine.
3. A process according to claim 1, wherein the lysine used is DL-lysine.
4. A process according to claims 1, 2 or 3, wherein the salt obtained is isolated by concentrating or cooling the reaction medium.
S. A process according to claims 1, 2 or 3, wherein the salt obtained is isolated by treating the reaction medium with a non-solvent.
6. The lysine salts of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid, having the following structural formula:
whenever prepared by a process according to claim l or its obvious chemical equivalents.
whenever prepared by a process according to claim l or its obvious chemical equivalents.
7. The L-lysine salt of 5-(p-chlorobenzoyl) 1,4-dimethyl-pyrrole-2-acetic acid, whenever prepared by a process according to claim 2 or its obvious chemical equivalents.
8. The DL-lysine salt of 5-(p-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid, whenever prepared by a process according to claim 3 or its obvious chemical equivalents.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT21949/81A IT1137229B (en) | 1981-05-26 | 1981-05-26 | ANALGESIC ACTIVITY SOLUBLE COMPOUND |
| IT21949A/81 | 1981-05-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1171421A true CA1171421A (en) | 1984-07-24 |
Family
ID=11189271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000403645A Expired CA1171421A (en) | 1981-05-26 | 1982-05-25 | Lysine salts having analgesic activity |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS57200359A (en) |
| KR (1) | KR860000292B1 (en) |
| BE (1) | BE893039A (en) |
| CA (1) | CA1171421A (en) |
| DE (1) | DE3219605A1 (en) |
| ES (1) | ES8302653A1 (en) |
| FR (1) | FR2506766A1 (en) |
| GB (1) | GB2098989B (en) |
| IT (1) | IT1137229B (en) |
| PT (1) | PT74949B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1210673B (en) * | 1982-02-26 | 1989-09-20 | Medosan Ind Biochimi | PYROLACETIC STARCHES ANTI-INFLAMMATORY ACTIVITY |
| IT1197688B (en) * | 1983-07-29 | 1988-12-06 | Medosan Ind Biochimi | ANTI-FLOGISTIC, ANALGESIC, ANTIPIRETIC AND ANTI-AGGREGATING PLASTER ACTIVITY OF 1-METHYL-5-METHYLBENZOYLPYRROL-2-ACETAMIDE ACETANILIDI |
| DE3328401A1 (en) * | 1983-08-05 | 1985-02-21 | Merckle GmbH, 7902 Blaubeuren | INJECTABLE SOLUTION FOR TREATING INFLAMMATION |
| US4873340A (en) * | 1986-05-29 | 1989-10-10 | Syntex (U.S.A.) Inc. | Process for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-A]pyrrole-1,1-dicarboxylates |
| US4988822A (en) * | 1986-05-29 | 1991-01-29 | Syntex (U.S.A.) Inc. | Intermediates for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo(1,2-A)pyrrole-1,1-dicarboxylates |
| GB8819569D0 (en) * | 1988-08-17 | 1988-09-21 | Dow Corning Ltd | Emulsions for treating fibrous materials |
| KR100898501B1 (en) * | 2007-09-03 | 2009-05-21 | 윤주평 | Solar tracking device using CDS device |
| KR101091936B1 (en) * | 2009-08-31 | 2011-12-08 | 에스디엔 주식회사 | Apparatus for detecting sunlight incident angle using pyranometer sensor |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4213905A (en) * | 1979-06-25 | 1980-07-22 | Mcneilab, Inc. | Preparation of 5-aroyl-1-loweralkylpyrrole-2-acetic acid salts |
-
1981
- 1981-05-26 IT IT21949/81A patent/IT1137229B/en active
-
1982
- 1982-04-30 BE BE0/207975A patent/BE893039A/en not_active IP Right Cessation
- 1982-05-19 GB GB8214547A patent/GB2098989B/en not_active Expired
- 1982-05-24 PT PT74949A patent/PT74949B/en unknown
- 1982-05-25 FR FR8209026A patent/FR2506766A1/en active Pending
- 1982-05-25 ES ES512510A patent/ES8302653A1/en not_active Expired
- 1982-05-25 CA CA000403645A patent/CA1171421A/en not_active Expired
- 1982-05-25 DE DE19823219605 patent/DE3219605A1/en not_active Withdrawn
- 1982-05-26 JP JP57089594A patent/JPS57200359A/en active Pending
- 1982-05-26 KR KR828202319A patent/KR860000292B1/en active
Also Published As
| Publication number | Publication date |
|---|---|
| GB2098989B (en) | 1984-10-10 |
| ES512510A0 (en) | 1983-02-01 |
| KR860000292B1 (en) | 1986-03-26 |
| FR2506766A1 (en) | 1982-12-03 |
| ES8302653A1 (en) | 1983-02-01 |
| KR830010067A (en) | 1983-12-26 |
| JPS57200359A (en) | 1982-12-08 |
| GB2098989A (en) | 1982-12-01 |
| DE3219605A1 (en) | 1982-12-23 |
| PT74949B (en) | 1983-12-23 |
| IT8121949A0 (en) | 1981-05-26 |
| PT74949A (en) | 1982-06-01 |
| BE893039A (en) | 1982-08-16 |
| IT1137229B (en) | 1986-09-03 |
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Legal Events
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| MKEC | Expiry (correction) | ||
| MKEX | Expiry |