IE46602B1 - Water-soluble corticoids - Google Patents
Water-soluble corticoidsInfo
- Publication number
- IE46602B1 IE46602B1 IE672/78A IE67278A IE46602B1 IE 46602 B1 IE46602 B1 IE 46602B1 IE 672/78 A IE672/78 A IE 672/78A IE 67278 A IE67278 A IE 67278A IE 46602 B1 IE46602 B1 IE 46602B1
- Authority
- IE
- Ireland
- Prior art keywords
- methyl
- pregnadien
- dioxo
- hydroxy
- fluoro
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0023—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16
- C07J5/003—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes
- C07J5/0038—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes by an alkyl group
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
Novel, water-soluble corticoids have the following formula in which n denotes the figures 2 or 3, X denotes hydrogen, fluorine or chlorine and Y denotes hydrogen, an alkali metal atom or the N-methylglucamine radical. The compounds of the formula I are obtained by partially esterifying a corresponding 21-hydroxycorticoid with succinic anhydride or glutaric anhydride. Medicaments which contain a compound of the formula I as the active compound component can be used for the treatment of shock after an accident, burns, operation wounds, circulatory failure after intoxications, cardiac infarcts, pulmonary embolism and asthma.
Description
PATENT APPLICATION BY (71) SCHERING AKTIENGESELLSCHAFT, A GERMAN BODY CORPORATE OF BERLIN AND BERGKAMEN, FEDERAL REPUBLIC OF GERMANY.
Price 90p
46002
The present invention is concerned with new water-soluble corticoids and with their manufacture and use.
The present invention provides compounds of the general formula I.
CHgOCO (CH2)nC00Y
F
. in which n represents 2 or 3
X represents a hydrogen atom, a fluorine atom or a chlorine atom and (
Y represents a hydrogen atom, an alkali metal atom,
. or an N-methylglucamine group, with the proviso that
Y does not represent a hydrogen atom when n represents 2 and X represents a hydrogen atom.
The new water-soluble corticoids are characterized by a favourable relation between therapeutic effect and tolerance. As compared
. with known water-soluble derivatives of corticoids of the general formula II given below (British Patent Specification
No. 1,286,093) the new corticoids are distinguished by a substantially more rapid inception of their action.
The therapeutic activity of the new water-soluble corticoids can be determined, for example, by the known endotoxin-shock test, the eosinophilic test or the adjuvant-oedema
. test. For determining the undesired systemic side effects, and therefore the tolerance of the new corticoids, there may be used, for example, the known thymolysis test, the liver glycogen test or the sodium-potassium retention test or the tolerance tesfr
. The present invention accordingly also provides a pharmaceutical preparation which comprises a compound of the general formula 1, in admixture or conjunction with a pharmaceutically suitable carrier. The preparation may, if desired, be in a form suitable for intravenous administration.
. The new water-soluble corticoids of the present invention may be worked up into pharmaceutical preparations in the usual manner by converting them, if desired with suitable additives carrier substances, solubilizers, stablizers and taste correctives, into the desired forms of application, for example
. tablets, dragees, capsules and solutions.
-4Thus, for example, definite quantities of the water-soluble corticoids, if desired after the addition of the usual adjuvants, may be introduced as dry substances into ampoules under the conditions conventionally used in galenical pharmacy, the ampoules preferably each containing a quantity of active substance within the range of from 10 mg to 500 mg. Before application the contents of the ampoule are dissolved in sterile distilled water.
The pharmaceutical preparations may be used preferably for the treatment of acute threatening states of disease (for example shock after accident, burns, operations, circulatory break-downs after poisonings, cardiac infarction, pulmonary embolism and severe attacks of asthma).
for treatment there may be administered intravenously to the patients preferably 10 to 1000 mg of active substance depending on the severity of the state of disease.
The new corticoids may be produced by a type of process well known to the expert, for example by the process of the present invention, as defined below.
The present invention accordingly further provides a process for the manufacture of a compound of the general formula I, as defined above, wherein a compound of the general formula
II
466 02
in which X has the meaning given above, is esterified in the 21-position with succinic anhydride or glutaric anhydride and, if desired or necessary, the resulting compound of the general formula I in which Y represents a hydrogen atom is
. converted into an alkali metal salt or N-methylglucamine salt thereof.
The reaction with the succinic anhydride or glutaric anhydride may be carried out in the presence of a base, for example pyridine, lutidine, potassium bicarbonate, sodium carbonate,
. potassium carbonate, sodium hydroxide or potassium hydroxide. The optional or necessary subsequent conversion into an alkali metal salt may be effected by raction with an alkali metal hydroxide, alkali metal carbonate, alkali metal bicarbonate or alkali metal alcoholate.
By. the process of the present invention there can be produced, for example:
(6a,9a - difluoro - 11β - hydroxy - 16a - methyl - 3,20 dioxo - Δ1,4 _ pregnadien - 21 - yl) - hemiglutarate, 5 also its sodium and potassium salts, and also (9a - chloro
- 6a - fluoro - 113 - hydroxy - 16a - methyl - 3,20 - dioxo -Δ^·4- pregnadien - 21 - yl) - hemiglutarate and its sodium and potassium salts.
The following examples illustrate the invention:EXAMPLE 1
Ιθ. (a) 2 Gms of 6α,9a - difluoro - 113,21 - dihydroxy - 16a methyl - Δ^'4- pregnadiene - 3,20 - dione were dissolved in 10 ml of pyridine, 1 gm of succinic anhydride was added and the whole was heated at the boil for 30 minutes while gassing with argon. After cooling, the mixture was stirred
. into ice-water, and acidified with dilute sulphuric acid, and the precipitated product was filtered off with suction, washed until neutral and dried. After recrystallization from acetonehexane 2.1 gms of (6α,9a - difluoro - 113 1 4 hydroxy - 16a - methyl - 3,20 - dioxo - Δ - pregnadien 20. 21 - yl) - hemisuccinate melting at 199—201°C were obtained.
466U2 (b) 700 Mg of the hemisuccinate in 10 ml of absolute methanol were adjusted with 9.4 ml of a 0.1 normal solution of potassium methylate to pH 8 using a pHmeter. The solution was concentrated in vaeuo and percipitated
, in 600 ml of ether. The precipitated potassium salt was filtered off with suction, washed with ether and dried over phosphorus pentoxide in vaeuo. 670 Mg of potassium (6α,9a -difluoro-Πβ - hydroxy - 16a - methyl - 3,20 1 4 dioxo - Δ ' - pregnadien - 21 - yl) - succinate melting
. at 170—180°C were obtained.
UV: ε23θ=16,600.
(c) 650 Mg of the hemisuccinate were adjusted in 10 ml of absolute methanol with 11.4 ml of a 0.1 normal sodium methylate solution to pH 8. The solution was concentrated
. in vaeuo, and stirred into a mixture, cooled to +3°C, of 500 ml of ether and 100 ml of pentane. The precipitated product was filtered off with suction and dried in vaeuo.
630 Mg of sodium (6α,9a - difluoro - Πβ - hydroxy - 16a - methyl - 3,20 - dioxo - Δ^'^ - pregnadien - 21 - yl) 2 0. succinate melting at 175—180°C were obtained.
UV: ε23θ=16,500.
EXAMPLE 2 (a) 5 Gms of 6a- fluoro - Πβ,21 - dihydroxy - 16a 1 4 methyl - Δ ' - pregnadiene - 3,20 - dione in 25 ml of pyridine were reacted with 5 gms of succinic anhydride in a manner analogous to that described in Examplel(a) and worked up. After recrystallization from ethyl acetate 5.2 gms of (6a - fluoro - 118 - hydroxy - 16a methyl - 3,20 - dioxo - Δ^'4 - pregnadien - 21 - yl) hemisuccinate o
. melting at 210—212 C were obtained.
(b) 10 gms of the hemisuccinate in 400 ml of absolute methanol were adjusted with 17.9 ml of a 0.1 normal solution of sodium methylate to pH 8 and precipitated as described in
Example 1(c). 9.6 gms of sodium (6a - fluoro - 116 - hydroxy 10. 16a - methyl - 3,20 - dioxo - - pregnadien - 21 - yl) succinate were obtained.
UV: ε242=16,100 melting point: 163—170°C (with decomposition).
EXAMPLE 3 (a) 5 Gms of 6a - fluoro - 118,21 - dihydroxy - 16a - methyl Δ^'4 - pregnadiene - 3,20 - dione in 20 ml of pyridine were
. heated at the boil with 2 gms of glutaric anhydride for minutes while gassing with argon. After cooling, the mixture was stirred into ice-water, and acidified with dilute sulphuric acid, and the precipitated product was filtered off with suction, washed until neutral and dried. The crude product
I
. Was dissolved in ethyl acetate and extracted by agitation with a sodium carbonate solution of 5% strength. The separated aqueous phase was acidified with hydrochloric acid, and extracted with ethyl acetate, and the ethyl acetate extract was washed
466 02 until neutral and evaporated in vaeuo. 5.2 gms of (6a - fluoro - 116 - hydroxy - 16a - methyl - 3,20 dioxo - Δ1’4 - pregnadien - 21 - yl) - hemiglutarate were obtained.
Melting point: 171—173°C.
. (b) 2.5 gms of the hemiglutarate were converted into the sodium salt in a manner analogous to that described in Example 1(c). 2.4 gms of sodium (6a - fluoro - 116 - hydroxy 16a - methyl - 3,20 - dioxo - Δ^'^ - pregnadien - 21 - yl)
- glutarate were obtained.
, UV: ε24ΐ=16,000. Melting point: 167°C (with decomposition).
EXAMPLE 4 (a) 1 Gm of 9a - chloro - 6a - fluoro - 116,21 - dihydroxy 16a - methyl - Δ1'4 - pregnadiene - 3,20 - dione in 5 ml of pyridine was heated at the boil with 0.5 gm of succinic anhydride for 30 minutes while gassing with argon. After working up
. as described in Example 1(a) and recrystallization from acetoneethyl acetate 1.23 gms of (9a - chloro - 6a - fluoro 116 - hydroxy - 16a - methyl - 3,20 - dioxo - Δ1,4- pregnadien
- 21 - yl) - hemisuccinate melting at 249°C (with decomposition) were obtained.
. (b) 700 mg of the hemisuccinate in 15 ml of methanol were converted with a 0.1 normal solution of sodium methylate into the sodium salt. 570 Mg of sodium (9a - chloro 6a - fluoro - 116 - hydroxy - 16a - methyl - 3,20 - dioxo 1 4
A ‘ - pregnadien - 21 - yl) - succinate were obtained.
. Melting point:165°C (with decomposition).
EXAMPLE 5
In a manner analogous to that described in Example 3 9a - chloro - 6a - fluoro - 11β,21 - dihydroxy - 16a methyl - Δ^'^ - pregnadiene - 3,20 - dione was converted into (9a - chloro - 6a - fluoro - 11β - hydroxy - 16a 5. methyl - 3,20 - dioxo - Δ1'4 - pregnadien - 21 - yl) hemiglutarate (melting at 182—183.5°C with decomposition) and the latter was further reacted to form sodium (9a chloro - 6a - fluoro - Πβ - hydroxy - 16a - methyl - 3,20 dioxo - - pregnadien - 21 - yl) - glutarate.
. Melting point: 124°C (with decomposition).
EXAMPLE 6.
1.5 gms of (6a - fluoro - Πβ - hydroxy - 16a - methyl - 3,20 - dioxo - Δ1'^ - pregnadien - 21 - yl) - hemisuccinate and 0.646 gm of N - methyl - glucamine were dissolved in 30 ml of bidistilled water and the clear solution was freeze-dried
. for 24 hours. 2.07 gms of amorphous N-methylglucamine (6a - fluoro - 11β - hydroxy - 16a - methyl - 3,20 - dioxo - pregnadien - 21 - yl) - succinate were obtained.
Claims (27)
1. WHAT WE CLAIM IS:1. A compound of the general formula I. j! in which n represents
2. Or 3. X represents a hydrogen atom a fluorine atom or a chlorine 5. atom and Y represents a hydrogen atom, an alkali metal atom or an N-methylglucamine group, with the proviso that Y does not represent a hydrogen atom when n represents 2 and X represents a hydrogen atom. 10· 2. Sodium (6α9α - difluoro - 113 - hydroxy - 16a - methyl 3,20 - dioxo - - pregnadien - 21 - yl) - succinate.
3. Sodium (6a - fluoro - 116 - hydroxy - 16a - methyl 3,20 - dioxo - Δ 1 ’ 3 4 - pregnadien - 21 - yl) - succinate. 46603 12
4. Sodium (6α - fluoro - 11β - hydroxy - 16α - methyl 1 4 3,20 - dioxo - Δ - pregnadien - 21 - yl) - glutarate.
5. Sodium (9a - chloro - 6a - fluoro - 11β - hydroxy 1 4 16a - methyl - 3,20 - dioxo - Δ ' - pregnadien - 21 -yl) 5. succinate.
6. Potassium (6α,9a - difluoro - 11β - hydroxy - 16a methyl - 3,20 - dioxo - Δ 1 ' 4 - pregnadien - 21 - yl) succinate.
7. (6α,9a - Difluoro - 11β - hydroxy - 16a - methyl - 3,20 1 4 10. dioxo - Δ - pregnadien - 21 - yl) - hemisuccinate.
8. (6a - Fluoro - 11β - hydroxy - 16a - methyl - 3,20 1 4 dioxo - Δ ' - pregnadien - 21 - yl) - hemiglutarate.
9. (9a - Chloro - 6a - fluoro - Πβ - hydroxy - 16a methyl - 3,20 - dioxo - Δ^’^ - pregnadien - 21 - yl) 15. hemisuccinate.
10. Sodium (9a - chloro - 6a - fluoro -
11. Β - hydroxy 1 4 16a - methyl - 3,20 - dioxo - Δ ' - pregnadien - 21 - yl) glutarate. 20. Π. N-Methylglucamine (6a - fluoro - Πβ - hydroxy - 16a 1 4 methyl - 3,20 - dioxo - Δ * - pregnadien - 21 - yl) succinate.
12. (9α - chloro - 6α - fluoro - llg - hydroxy - 16α methyl - 3,20 - dioxo - Δ^’ 4 - pregnadien - 21 - yl) 'hemigl utarate.
13. Potassium (9a - chloro - 6a - fluoro - llg - hydroxy 5· 16a - methyl - 3,20 - dioxo - Δ^' 4 - pregnadien - 21 - yl) glutarate.
14. (6α,9a - Difluoro - llg - hydroxy - 16a - methyl 1 4 3,20 - dioxo - Δ ’ - pregnadien -21 - yl) - hemiglutarate.
15. Sodium (6α,9a - difluoro - llg - hydroxy - 16a 10. methyl - 3,20 - dioxo - Δ^' 4 - pregnadien -21 - yl) glutarate.
16. Potassium (6α,9a - difluoro - llg - hydroxy - 16a methyl - 3,20 - dioxo - Δ^' 4 - pregnadien - 21 - yl) glutarate. 15.
17. A pharmaceutical preparation which comprises a compound as claimed in claim 1, in admixture or conjunction with a pharmaceutically suitable carrier.
18. A pharmaceutical preparation which comprises the compound claimed in any one of claims 2 to 16, in admixture or conjunction 20. with a pharmaceutically suitable carrier.
19. A preparation as claimed in claim 17 or 18, which is in a form suitable for intravenous administration.
20. A preparation as claimed in claim 17 or 18, which is in the form of a tablet, dragee, capsule or solution. 5.
21. A preparation as claimed in claim 17 or 18, which is in the form of an ampoule.
22. A preparation as claimed in claim 21, wherein the quantity of active substance present in the ampoule is within the range of from 10 mg to 500 mg. 10.
23. A process for the manufacture of a compound of the general formula I given in claim 1, in which η, X and Y have the meanings given in claim 1, wherein a compound of the general formula II. ι ι F - 15 46602 in which X has the meaning given above, is esterified in the 21position with succinic anhydride or glutaric anhydride and, if desired or necessary, the resulting compound of the general formula I in which Y represents a hydrogen atom is converted 5 · into an alkali metal salt or N-methylglucamine salt thereof.
24. A process as claimed in claim 23, wherein the esterification is carried out in the presence of a base.
25. A process as claimed in claim 23 or 24, wherein the conversion into the alkali metal salt is carried out by reaction 10. with an alkali metal hydroxide, an alkali metal carbonate, an alkali metal bicarbonate or an alkali metal alcoholate.
26. A process as claimed in claim 23, conducted substantially as described in any one of Examples 1 to 3 herein.
27. A process as claimed in claim 23 conducted substantially 15. as described in any one of Examples 4 to 6 herein.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772715853 DE2715853A1 (en) | 1977-04-06 | 1977-04-06 | WATER-SOLUBLE CORTICOIDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE780672L IE780672L (en) | 1978-10-06 |
| IE46602B1 true IE46602B1 (en) | 1983-07-27 |
Family
ID=6005979
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE672/78A IE46602B1 (en) | 1977-04-06 | 1978-04-05 | Water-soluble corticoids |
Country Status (29)
| Country | Link |
|---|---|
| JP (1) | JPS53149963A (en) |
| AT (1) | ATA239978A (en) |
| AU (1) | AU3481178A (en) |
| BE (1) | BE865760A (en) |
| BG (1) | BG28578A3 (en) |
| CA (1) | CA1113452A (en) |
| CH (1) | CH638537A5 (en) |
| CS (1) | CS198295B2 (en) |
| DD (1) | DD135082A5 (en) |
| DE (1) | DE2715853A1 (en) |
| DK (1) | DK153378A (en) |
| EG (1) | EG13249A (en) |
| ES (1) | ES468572A1 (en) |
| FI (1) | FI781053A (en) |
| FR (1) | FR2386557A1 (en) |
| GB (1) | GB1602266A (en) |
| IE (1) | IE46602B1 (en) |
| IL (1) | IL54443A0 (en) |
| IT (1) | IT1094296B (en) |
| LU (1) | LU79375A1 (en) |
| NL (1) | NL7803188A (en) |
| NO (1) | NO781200L (en) |
| NZ (1) | NZ186745A (en) |
| PL (1) | PL114096B1 (en) |
| PT (1) | PT67872B (en) |
| RO (1) | RO81076A2 (en) |
| SE (1) | SE7803837L (en) |
| SU (1) | SU668611A3 (en) |
| ZA (1) | ZA781977B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4948533A (en) * | 1984-03-28 | 1990-08-14 | The Upjohn Company | 11a-hydroxy steroid diester |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1169444B (en) * | 1961-02-22 | 1964-05-06 | Schering Ag | Process for the preparation of ?-16ª‡-methyl steroids |
| YU34304B (en) * | 1968-08-17 | 1979-04-30 | Schering Ag | Process for preparing corticoid-21-mono-phosphates |
| DK290774A (en) * | 1973-06-08 | 1975-02-03 | Schering Ag |
-
1977
- 1977-04-06 DE DE19772715853 patent/DE2715853A1/en not_active Withdrawn
-
1978
- 1978-03-21 NZ NZ186745A patent/NZ186745A/en unknown
- 1978-03-23 NL NL7803188A patent/NL7803188A/en not_active Application Discontinuation
- 1978-03-29 DD DD78204456A patent/DD135082A5/en unknown
- 1978-03-30 SU SU782595445A patent/SU668611A3/en active
- 1978-03-31 BG BG7839252A patent/BG28578A3/en unknown
- 1978-04-03 CH CH357378A patent/CH638537A5/en not_active IP Right Cessation
- 1978-04-04 LU LU79375A patent/LU79375A1/en unknown
- 1978-04-04 IL IL54443A patent/IL54443A0/en unknown
- 1978-04-04 RO RO7893718A patent/RO81076A2/en unknown
- 1978-04-04 PL PL1978205800A patent/PL114096B1/en unknown
- 1978-04-05 AU AU34811/78A patent/AU3481178A/en active Pending
- 1978-04-05 AT AT0239978A patent/ATA239978A/en not_active Application Discontinuation
- 1978-04-05 IE IE672/78A patent/IE46602B1/en unknown
- 1978-04-05 IT IT21995/78A patent/IT1094296B/en active
- 1978-04-05 ES ES468572A patent/ES468572A1/en not_active Expired
- 1978-04-05 CA CA300,512A patent/CA1113452A/en not_active Expired
- 1978-04-05 PT PT67872A patent/PT67872B/en unknown
- 1978-04-05 SE SE7803837A patent/SE7803837L/en unknown
- 1978-04-05 NO NO781200A patent/NO781200L/en unknown
- 1978-04-05 EG EG239/78A patent/EG13249A/en active
- 1978-04-06 GB GB13527/78A patent/GB1602266A/en not_active Expired
- 1978-04-06 FI FI781053A patent/FI781053A/en not_active Application Discontinuation
- 1978-04-06 ZA ZA00781977A patent/ZA781977B/en unknown
- 1978-04-06 CS CS782252A patent/CS198295B2/en unknown
- 1978-04-06 FR FR7810202A patent/FR2386557A1/en active Granted
- 1978-04-06 JP JP4077278A patent/JPS53149963A/en active Pending
- 1978-04-06 DK DK153378A patent/DK153378A/en not_active IP Right Cessation
- 1978-04-06 BE BE186622A patent/BE865760A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IT1094296B (en) | 1985-07-26 |
| BG28578A3 (en) | 1980-05-15 |
| PT67872A (en) | 1978-05-01 |
| NZ186745A (en) | 1980-10-24 |
| BE865760A (en) | 1978-10-06 |
| CH638537A5 (en) | 1983-09-30 |
| NL7803188A (en) | 1978-10-10 |
| NO781200L (en) | 1978-10-09 |
| FI781053A (en) | 1978-10-07 |
| JPS53149963A (en) | 1978-12-27 |
| DE2715853A1 (en) | 1978-10-19 |
| RO81076A2 (en) | 1983-02-01 |
| IL54443A0 (en) | 1978-07-31 |
| SU668611A3 (en) | 1979-06-15 |
| FR2386557A1 (en) | 1978-11-03 |
| RO81076B1 (en) | 1983-01-30 |
| DK153378A (en) | 1978-10-07 |
| ES468572A1 (en) | 1978-12-01 |
| CS198295B2 (en) | 1980-05-30 |
| GB1602266A (en) | 1981-11-11 |
| PL205800A1 (en) | 1979-01-29 |
| FR2386557B1 (en) | 1980-02-01 |
| AU3481178A (en) | 1979-10-11 |
| LU79375A1 (en) | 1978-07-13 |
| DD135082A5 (en) | 1979-04-11 |
| IE780672L (en) | 1978-10-06 |
| ZA781977B (en) | 1979-03-28 |
| ATA239978A (en) | 1981-06-15 |
| SE7803837L (en) | 1978-10-07 |
| PT67872B (en) | 1979-11-14 |
| PL114096B1 (en) | 1981-01-31 |
| EG13249A (en) | 1980-12-31 |
| IT7821995A0 (en) | 1978-04-05 |
| CA1113452A (en) | 1981-12-01 |
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