CA1230549A - Contrast medium - Google Patents
Contrast mediumInfo
- Publication number
- CA1230549A CA1230549A CA000461708A CA461708A CA1230549A CA 1230549 A CA1230549 A CA 1230549A CA 000461708 A CA000461708 A CA 000461708A CA 461708 A CA461708 A CA 461708A CA 1230549 A CA1230549 A CA 1230549A
- Authority
- CA
- Canada
- Prior art keywords
- barium sulfate
- contrast medium
- weight
- ray contrast
- crystals
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0404—X-ray contrast preparations containing barium sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Apparatus For Radiation Diagnosis (AREA)
- Analysing Materials By The Use Of Radiation (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
X-ray contrast media comprising barium sulfate and a synergistic liquefier combination of a ligninsulfonic acid or sulfonate and an alkali metal citrate.
X-ray contrast media comprising barium sulfate and a synergistic liquefier combination of a ligninsulfonic acid or sulfonate and an alkali metal citrate.
Description
~;~30~9 The present invention relates to an x-ray contrast medium comprlsing barium sulfate as a contrast agent and a synergistic mixture of a ligninsulfonic acid or sulfonate and an alkali metal citrate for reducing the viscosity of an aqueous suspension of the contrast agent and enhancing its stability to stomach acid.
Contrast media containing ligninsulfonic acid or water soluble salts thereof in an amount ranging from 0.1 to 3 weight percent, based on the barium sulfate, are known from German patent 2,028,025. An aqueous suspension of such an agent is stable even in the acidic medium of the stomach and thus assures good radiographs of the gastrointestinal tract.
It is known from U.S. patent 3,216,900 to prepare barium sulfate suspensions containing sodium citrate as a viscosity reducing additive. The addition of 1 percent of sodium citrate results in a suspension of suitable viscosity (efflux time in conformity with the German Pharmacopoeia, 8th ed. = 33 sec) containing 1.9 grams/liter of barium sulfate. However, the suspension is unstable in the acidic medium of the stomach. [See H. Wang and X. Hu, Yaoxue Xuebao 16, 610 (1981), abstracted in Chem. Abstr. 96, 57732.]
The definition, or sharpness, of radiographs could be increased further if a suspension of a contrast agent having higher concentrations of barium sulfate were available. Heretofore the high viscosity of highly concentrated barium sulfate suspensions has militated against their use. Thus, there has been a need for a 1230~49 contrast medium whieh gives acid resistant aqueous suspensions -that have a higher barium sulfate concentration, yet a viscosity suitable for diagnostic purposes.
It has now been found that ligninsulfonic acid, or the water soluble salts thereof, and alkali metal citrates cooperate synergistieally. When used together in an X-ray contrast medium, aqueous barium sulfate suspensions are obtained which would not be possible with ligninsulfonic acid or ligninsulfonates alone. Such suspensions are stable in the acidic medium of the stomach. While with ligninsulfonic acid or ligninsulfonates a barium sulfate content of 2 g/ml cannot be exceeded if a viscosi-ty of 60 sec (efflux time in conformity with the German Pharmacopoeia, ~th ed.) is to be attained, a eoneentration of 2.5 g/ml with the same efflux time is obtained when the same barium sulfate preparation is used in aeeordanee with the present invention.
Statement of Invention In aeeordanee with the invention there is provided an X-ray eontrast agent in the form of an aqueous suspension, or in the form of a dry powder which can be mixed with water to form an aqueous suspension, comprising barium sulfate, 0.02 to 3 pereent of ligninsulfonie acid or a water soluble salt thereof and 0.05 to 3 percent of alkali citrate, by weight of the barium sulfate, wherein the ratio by weight of ligninsulfonic acid or salt to alkali citrate is between 3 : 1 and 1 : 10.
i_=, .,~. ,~i 1~:30549 According to one embodiment of -the invention the X-ray contrast medium comprises crystals of barium sulfate in a bimodal particle size distribution which includes coarser and finer crystals, the coarser crystals ranging in size from 5 to 20 microns and the finer crystals ranging in size from 0.2 to 5 microns, the ratio by weight of the coarser crystals to the finer crystals being between 20 : 1 and 1 : 20.
- 2a -~
TAsl.E I
COMPONENT (GRAMS~ A B C
. _ _ . _ _ _ _ _ sarium sulfate for X-ray purposes (average particle slze: 10 microns) 758.0 758.0 758.0 Barium sul:Eate for X-ray purposes (average particle size: 1 micron) 189.5 189.5 189.5 Sorbitol. 20.0 20.0 20.0 Sodium citrate - 10.0 5.0 Sodium ligninsulfonate10.0 - 5.0 Sodium cyclamate (sweetener) 0.5 0.5 0.5 Silicon, defoaming agent2.0 2.0 2.0 Water 196.0 196.0 196.0 Efflux time (in conformity with the German Pharmacopoeia, 8th Edition) (in seconds) 152 50 45 The following viscositles were determined for an aqueous suspension of barlum sulfate containing barium sulfate crystals of mono-d.isperse particle size distribution and an average particle size of one micron and (by weight of the barium sulfate) 2.1% of sorbitol, 0.05% of sodium cyclamate, 0.2% of a defoaming agent, and 3~ of a mixture of sodium ligninsulfonate and sodium citrate. More in particular, the viscosity was determined in dependence on the mixing ratios of the two last-mentioned components.
12305~9 TABLE II
Ratio By Weight of Viscosity (Efflux time Sodium ligninsulfonate: in Seconds, German Sodium citrate Pharmacopoeia, 8th Edition) 1 : 0 86 5 : l 87
Contrast media containing ligninsulfonic acid or water soluble salts thereof in an amount ranging from 0.1 to 3 weight percent, based on the barium sulfate, are known from German patent 2,028,025. An aqueous suspension of such an agent is stable even in the acidic medium of the stomach and thus assures good radiographs of the gastrointestinal tract.
It is known from U.S. patent 3,216,900 to prepare barium sulfate suspensions containing sodium citrate as a viscosity reducing additive. The addition of 1 percent of sodium citrate results in a suspension of suitable viscosity (efflux time in conformity with the German Pharmacopoeia, 8th ed. = 33 sec) containing 1.9 grams/liter of barium sulfate. However, the suspension is unstable in the acidic medium of the stomach. [See H. Wang and X. Hu, Yaoxue Xuebao 16, 610 (1981), abstracted in Chem. Abstr. 96, 57732.]
The definition, or sharpness, of radiographs could be increased further if a suspension of a contrast agent having higher concentrations of barium sulfate were available. Heretofore the high viscosity of highly concentrated barium sulfate suspensions has militated against their use. Thus, there has been a need for a 1230~49 contrast medium whieh gives acid resistant aqueous suspensions -that have a higher barium sulfate concentration, yet a viscosity suitable for diagnostic purposes.
It has now been found that ligninsulfonic acid, or the water soluble salts thereof, and alkali metal citrates cooperate synergistieally. When used together in an X-ray contrast medium, aqueous barium sulfate suspensions are obtained which would not be possible with ligninsulfonic acid or ligninsulfonates alone. Such suspensions are stable in the acidic medium of the stomach. While with ligninsulfonic acid or ligninsulfonates a barium sulfate content of 2 g/ml cannot be exceeded if a viscosi-ty of 60 sec (efflux time in conformity with the German Pharmacopoeia, ~th ed.) is to be attained, a eoneentration of 2.5 g/ml with the same efflux time is obtained when the same barium sulfate preparation is used in aeeordanee with the present invention.
Statement of Invention In aeeordanee with the invention there is provided an X-ray eontrast agent in the form of an aqueous suspension, or in the form of a dry powder which can be mixed with water to form an aqueous suspension, comprising barium sulfate, 0.02 to 3 pereent of ligninsulfonie acid or a water soluble salt thereof and 0.05 to 3 percent of alkali citrate, by weight of the barium sulfate, wherein the ratio by weight of ligninsulfonic acid or salt to alkali citrate is between 3 : 1 and 1 : 10.
i_=, .,~. ,~i 1~:30549 According to one embodiment of -the invention the X-ray contrast medium comprises crystals of barium sulfate in a bimodal particle size distribution which includes coarser and finer crystals, the coarser crystals ranging in size from 5 to 20 microns and the finer crystals ranging in size from 0.2 to 5 microns, the ratio by weight of the coarser crystals to the finer crystals being between 20 : 1 and 1 : 20.
- 2a -~
TAsl.E I
COMPONENT (GRAMS~ A B C
. _ _ . _ _ _ _ _ sarium sulfate for X-ray purposes (average particle slze: 10 microns) 758.0 758.0 758.0 Barium sul:Eate for X-ray purposes (average particle size: 1 micron) 189.5 189.5 189.5 Sorbitol. 20.0 20.0 20.0 Sodium citrate - 10.0 5.0 Sodium ligninsulfonate10.0 - 5.0 Sodium cyclamate (sweetener) 0.5 0.5 0.5 Silicon, defoaming agent2.0 2.0 2.0 Water 196.0 196.0 196.0 Efflux time (in conformity with the German Pharmacopoeia, 8th Edition) (in seconds) 152 50 45 The following viscositles were determined for an aqueous suspension of barlum sulfate containing barium sulfate crystals of mono-d.isperse particle size distribution and an average particle size of one micron and (by weight of the barium sulfate) 2.1% of sorbitol, 0.05% of sodium cyclamate, 0.2% of a defoaming agent, and 3~ of a mixture of sodium ligninsulfonate and sodium citrate. More in particular, the viscosity was determined in dependence on the mixing ratios of the two last-mentioned components.
12305~9 TABLE II
Ratio By Weight of Viscosity (Efflux time Sodium ligninsulfonate: in Seconds, German Sodium citrate Pharmacopoeia, 8th Edition) 1 : 0 86 5 : l 87
2 : 1 50 1 : 1 27 1 : 2 20 1 : 5 21 0 : 1 23 The synergistic effect of ligninsulfonic acid or ligninsulfonate and alkali citrate is observed in the region of weight ratios from 3 : 1 to 1 : 10 and is particularly outstanding in the region from 2 : 1 to 1 : 5. The effect, which simultaneously liquefies and stabilizes the combination against stomach acid, is particularly advantageous in suspensions having a barium sulfate content from 0.5 to 2.5 g/ml.
The barium sulfate contained in the new contrast medium may be of the grade long used for this purpose. A
commonly used particle size is about 1 micron. However, it will be advantageous to use a barium sulfate with a bimodal particle size distribution containing coarser and finer crystals. The particle size distribution of the mixture then will have two maxima, one in the range from 0.2 to 5 microns, the other in the range from 5 to 20 microns. The weight ratio of the coarser crystals to the finer crystals should range from 20:1 to 1:20 and preferably is 4:1~
05~9 The advantages of bimodal particle size distributions have been described by K. Hirai in Osaka ïka Daigaku Zasshi 35, 9S (1976) (abstracted in Chem. Abstr. 87, 106697), and W. Anderson et al. in J. Pharm. Pharmac. 31, 54 P (1979).
By the use of barium sulfate with a bimodal particle size distribution according to the present invention, low viscosity acid-resistant suspensions having a barium sulfate concentration of up to 2.5 g/ml can be obtained.
In accordance with the invention, ligninsulfonic acid is usually employed in a smaller amount than when it is used without the addition of an alkali metal citrate.
Namely, it is used in an amount ranging from 0.02 to
The barium sulfate contained in the new contrast medium may be of the grade long used for this purpose. A
commonly used particle size is about 1 micron. However, it will be advantageous to use a barium sulfate with a bimodal particle size distribution containing coarser and finer crystals. The particle size distribution of the mixture then will have two maxima, one in the range from 0.2 to 5 microns, the other in the range from 5 to 20 microns. The weight ratio of the coarser crystals to the finer crystals should range from 20:1 to 1:20 and preferably is 4:1~
05~9 The advantages of bimodal particle size distributions have been described by K. Hirai in Osaka ïka Daigaku Zasshi 35, 9S (1976) (abstracted in Chem. Abstr. 87, 106697), and W. Anderson et al. in J. Pharm. Pharmac. 31, 54 P (1979).
By the use of barium sulfate with a bimodal particle size distribution according to the present invention, low viscosity acid-resistant suspensions having a barium sulfate concentration of up to 2.5 g/ml can be obtained.
In accordance with the invention, ligninsulfonic acid is usually employed in a smaller amount than when it is used without the addition of an alkali metal citrate.
Namely, it is used in an amount ranging from 0.02 to
3 weight percent, and preferably from 0.05 to 1 weight percent, based on the barium sulfate. In the grade suitable for use in a contrast medium, ligninsulfonic acid is not always present in chemically pure form. The amount to be used depends on the actual ligninsulfonic acid content of the preparation employed. When water soluble salts of ligninsulfonic acid are used, the calculation of the amount should be based on the free acid alone. Among the water soluble salts, sodium ligninsulfonate is particularly preferred.
The preferred alkali metal citrate is sodium citrate. It is used in an amount ranging from 0.05 to 3 weight percent, based on the barium sulfate.
~:3QS~
Ligninsulfonic acid or sulfonates and an alkali metal citrate are suitably used in a combined total amount from 0.2 to 3 percent by weight of the barium sulfate.
The new contrast media may be marketed as a powdered mixture to be made into a paste with water just prior to use. However, they may also be marketed as an aqueous paste or as a more or less fluid aqueous preparation. The powdered dry products may be prepared by mixing the dry ingredients or by adding an aqueous solution of ligninsulfonic acid or ligninsulfonate and of alkali metal citrate to an aqueous barium sulfate suspension and then drying, and preferably spray drying, the suspension.
Moreover, additives which have also been used in the past in contrast media containing barium sulfate, for example, sucrose, sorbitol, bentonite, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, and alginates, as well as flavoring materials and defoaming agents may be admixed with the new contrast media.
A few appropriate formulations are presented below by way of example. The percentages refer to the total weight of the mixture. The ligninsulfonate used in these examples i5 a purified product which is about 60 percent pure.
947.5 g of barium sulfate for radiological use (average particle size, 1 micron), 20.0 g of sorbitol, 20.0 g of sodium citrate (about 2%), 10.0 g of sodium ligninsulfonate (about 1%), and 0.5 g of sodium cyclamate ~2~ 9 are homogeneously mixed. 250 g of the mixture are mixed with 70 ml of water. The contrast medium suspension contains 1.8 g of barium sulfate per milliliter.
The following components are mixed:
758.0 g of barium sulfate for radiological use (average particle size, 10 microns), 189.5 g of barium sulfate for radiological use (average particle size, 1 micron), 20.0 g of sorbitol, 5.0 g of sodium ligninsulfonate (about 0.5%), and 5.0 g of sodium citrate (about 0.5%).
250 g of the powdered mixture is mixed with 50 ml water and shaken in a closed vessel for 15 seconds. The barium sulfate concentration of the suspension so obtained is 2.2 g/ml. The efflux time is 45 sec.
1492.4 g of barium sulfate for radiological use (average particle size, 10 microns), 402.6 g of barium sulfate for radiological use (average particle size, 1 micron),
The preferred alkali metal citrate is sodium citrate. It is used in an amount ranging from 0.05 to 3 weight percent, based on the barium sulfate.
~:3QS~
Ligninsulfonic acid or sulfonates and an alkali metal citrate are suitably used in a combined total amount from 0.2 to 3 percent by weight of the barium sulfate.
The new contrast media may be marketed as a powdered mixture to be made into a paste with water just prior to use. However, they may also be marketed as an aqueous paste or as a more or less fluid aqueous preparation. The powdered dry products may be prepared by mixing the dry ingredients or by adding an aqueous solution of ligninsulfonic acid or ligninsulfonate and of alkali metal citrate to an aqueous barium sulfate suspension and then drying, and preferably spray drying, the suspension.
Moreover, additives which have also been used in the past in contrast media containing barium sulfate, for example, sucrose, sorbitol, bentonite, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, and alginates, as well as flavoring materials and defoaming agents may be admixed with the new contrast media.
A few appropriate formulations are presented below by way of example. The percentages refer to the total weight of the mixture. The ligninsulfonate used in these examples i5 a purified product which is about 60 percent pure.
947.5 g of barium sulfate for radiological use (average particle size, 1 micron), 20.0 g of sorbitol, 20.0 g of sodium citrate (about 2%), 10.0 g of sodium ligninsulfonate (about 1%), and 0.5 g of sodium cyclamate ~2~ 9 are homogeneously mixed. 250 g of the mixture are mixed with 70 ml of water. The contrast medium suspension contains 1.8 g of barium sulfate per milliliter.
The following components are mixed:
758.0 g of barium sulfate for radiological use (average particle size, 10 microns), 189.5 g of barium sulfate for radiological use (average particle size, 1 micron), 20.0 g of sorbitol, 5.0 g of sodium ligninsulfonate (about 0.5%), and 5.0 g of sodium citrate (about 0.5%).
250 g of the powdered mixture is mixed with 50 ml water and shaken in a closed vessel for 15 seconds. The barium sulfate concentration of the suspension so obtained is 2.2 g/ml. The efflux time is 45 sec.
1492.4 g of barium sulfate for radiological use (average particle size, 10 microns), 402.6 g of barium sulfate for radiological use (average particle size, 1 micron),
4.0 g of sodium citrate (about 0.2%), 2.0 g of sodium ligninsulfonate (about 0.1%), and 1.0 g of sodium cyclamate are mixed homogeneously. The mixture is screened. By mixing with ~e4 ml water, a contrast medium suspension ready for use is obtained.
123C)~49 59.70 kg of barium sulfate for radiological usD
(average particle size, lO microns), 16.10 kg of barium sulfate for radiological use (average particle size, 1 micron), 1.60 kg of sorbitol, 0.32 kg of sodium citrate (about 0.4%), 0.16 kg of sodium ligninsulfonate (about 0.2%~, and 0,16 kg of silicone defoamer are mixed for 25 minutes and then screened using a 2-mm mesh screen. 1 kg of this powdered mixture is then mixed with 180 ml water and mechanically agitated for 1 minute. The contrast medium suspension so obtained has a barium sulfate concentration of 2.3 g/ml and an efflux time of 50 sec.
758.0 g of barium sulfate for radiological use (average particle size, 10 microns), 189.5 g of barium sulfate for radiological use (average particle size, 0.7 microns), 20.0 g of sorbitol,
123C)~49 59.70 kg of barium sulfate for radiological usD
(average particle size, lO microns), 16.10 kg of barium sulfate for radiological use (average particle size, 1 micron), 1.60 kg of sorbitol, 0.32 kg of sodium citrate (about 0.4%), 0.16 kg of sodium ligninsulfonate (about 0.2%~, and 0,16 kg of silicone defoamer are mixed for 25 minutes and then screened using a 2-mm mesh screen. 1 kg of this powdered mixture is then mixed with 180 ml water and mechanically agitated for 1 minute. The contrast medium suspension so obtained has a barium sulfate concentration of 2.3 g/ml and an efflux time of 50 sec.
758.0 g of barium sulfate for radiological use (average particle size, 10 microns), 189.5 g of barium sulfate for radiological use (average particle size, 0.7 microns), 20.0 g of sorbitol,
5.0 g of sodium citrate (about 0.5~), 5.0 g of sodium ligninsulfonate (about 0.5%), 2.0 g of silicone defoamer are mixed and 250 g of the mixture are shaken in a closed vessel with 45 ml of wa-ter~ The contrast medium suspension so obtained contains 2.5 g of barium sulfate per milliliter and its efflux time is 60 sec.
Claims (7)
1. An X-ray contrast agent in the form of an aqueous suspension, or in the form of a dry powder which can be mixed with water to form an aqueous suspension, comprising barium sulfate, 0.02 to 3 percent of ligninsulfonic acid or a water soluble salt thereof and 0.05 to 3 percent of alkali citrate, by weight of said barium sulfate, wherein the ratio by weight of ligninsulfonic acid or salt to alkali citrate is between 3 : 1 and 1 : 10.
2. An X-ray contrast medium as in Claim 1 comprising crystals of barium sulfate in a bimodal particle size distribution which includes coarser and finer crystals, said coarser crystals ranging in size from 5 to 20 microns and said finer crystals ranging in size from 0.2 to 5 microns, the ratio by weight of the coarser crystals to the finer crystals being between 20 : 1 and 1 : 20.
3. An X-ray contrast medium as in Claim 1 wherein said ligninsulfonic acid or salt and said alkali citrate are present in a total amount from 0.2 to 3 percent, by weight of said barium sulfate.
4. An X-ray contrast medium as in Claim 1 wherein said ligninsulfonic acid or salt and said alkali citrate are present in a weight ratio from 2 : 1 to 1 : 5.
5. An X-ray contrast medium as in Claim 1 in the form of a powder.
6. An X-ray contrast medium as in Claim 1 in the form of an aqueous suspension.
7. An X-ray contrast medium as in Claim 6 comprising from 0.5 to 2.5 g/ml of barium sulfate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3330769A DE3330769A1 (en) | 1983-08-26 | 1983-08-26 | X-RAY CONTRASTING AGENTS |
| DEP3330769.5 | 1983-08-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1230549A true CA1230549A (en) | 1987-12-22 |
Family
ID=6207472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000461708A Expired CA1230549A (en) | 1983-08-26 | 1984-08-24 | Contrast medium |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0135765B1 (en) |
| JP (1) | JPS6061537A (en) |
| AT (1) | ATE58296T1 (en) |
| CA (1) | CA1230549A (en) |
| DD (1) | DD227048A5 (en) |
| DE (2) | DE3330769A1 (en) |
| ES (1) | ES533964A0 (en) |
| ZA (1) | ZA846625B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62153229A (en) * | 1985-12-27 | 1987-07-08 | Nippon Oil Co Ltd | Skin marker |
| JP3717007B2 (en) * | 1995-12-08 | 2005-11-16 | 和三 平井 | Novel barium powder formulation, ultra-high concentration barium suspension for upper gastrointestinal tract imaging using the same, and production method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3689630A (en) * | 1968-09-09 | 1972-09-05 | Sakai Chemical Industry Co | Barium sulfate contrast media |
| NL7500169A (en) * | 1975-01-07 | 1976-07-09 | Josephus Henricus Joannes Ruij | Combined radiography of gall bladder and gastro-intestinal tract - using an oil-contg. X-ray contrast agent |
-
1983
- 1983-08-26 DE DE3330769A patent/DE3330769A1/en not_active Withdrawn
-
1984
- 1984-07-03 ES ES533964A patent/ES533964A0/en active Granted
- 1984-08-10 EP EP84109534A patent/EP0135765B1/en not_active Expired - Lifetime
- 1984-08-10 DE DE8484109534T patent/DE3483597D1/en not_active Expired - Lifetime
- 1984-08-10 AT AT84109534T patent/ATE58296T1/en active
- 1984-08-16 DD DD84266333A patent/DD227048A5/en not_active IP Right Cessation
- 1984-08-21 JP JP59172548A patent/JPS6061537A/en active Pending
- 1984-08-24 CA CA000461708A patent/CA1230549A/en not_active Expired
- 1984-08-24 ZA ZA846625A patent/ZA846625B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6061537A (en) | 1985-04-09 |
| ATE58296T1 (en) | 1990-11-15 |
| ZA846625B (en) | 1985-04-24 |
| EP0135765A3 (en) | 1988-08-17 |
| ES8506453A1 (en) | 1985-08-16 |
| DE3330769A1 (en) | 1985-03-21 |
| EP0135765B1 (en) | 1990-11-14 |
| ES533964A0 (en) | 1985-08-16 |
| DD227048A5 (en) | 1985-09-11 |
| DE3483597D1 (en) | 1990-12-20 |
| EP0135765A2 (en) | 1985-04-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |