IE48192B1 - Pharmaceutical compositions containing an ergot alkaloid and heparin - Google Patents
Pharmaceutical compositions containing an ergot alkaloid and heparinInfo
- Publication number
- IE48192B1 IE48192B1 IE701/79A IE70179A IE48192B1 IE 48192 B1 IE48192 B1 IE 48192B1 IE 701/79 A IE701/79 A IE 701/79A IE 70179 A IE70179 A IE 70179A IE 48192 B1 IE48192 B1 IE 48192B1
- Authority
- IE
- Ireland
- Prior art keywords
- heparin
- formula
- compound
- pharmaceutical composition
- isopropyl
- Prior art date
Links
- 229920000669 heparin Polymers 0.000 title claims abstract description 24
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 229960002897 heparin Drugs 0.000 title claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- 229960003133 ergot alkaloid Drugs 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000002552 dosage form Substances 0.000 claims abstract 2
- 239000003085 diluting agent Substances 0.000 claims description 4
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 claims description 3
- 229960004704 dihydroergotamine Drugs 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 abstract description 3
- 239000007924 injection Substances 0.000 abstract description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 229930013930 alkaloid Natural products 0.000 abstract 1
- 150000003797 alkaloid derivatives Chemical class 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 239000008024 pharmaceutical diluent Substances 0.000 abstract 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 abstract 1
- ADYPXRFPBQGGAH-UMYZUSPBSA-N dihydroergotamine mesylate Chemical compound CS(O)(=O)=O.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C)C1=CC=CC=C1 ADYPXRFPBQGGAH-UMYZUSPBSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229940102223 injectable solution Drugs 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010050902 Postoperative thrombosis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- NQRDVLDEYJYWQR-SZGCSELGSA-N dihydroergovaline Chemical compound C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)C(C)C)C)=C3C2=CNC3=C1 NQRDVLDEYJYWQR-SZGCSELGSA-N 0.000 description 1
- -1 disodium hydrogen Chemical class 0.000 description 1
- KDQPSPMLNJTZAL-UHFFFAOYSA-L disodium hydrogenphosphate dihydrate Chemical compound O.O.[Na+].[Na+].OP([O-])([O-])=O KDQPSPMLNJTZAL-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000011363 dried mixture Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Saccharide Compounds (AREA)
Abstract
A pharmaceutical composition comprises a mixture of a hydrogenated ergot alkaloid of formula (I):- wherein R is hydrogen or a C1-4 alkyl group other than t-butyl; R1 is methyl, ethyl or isopropyl; R2 is isopropyl, secbutyl, isobutyl or benzyl; and X is hydrogen or methoxy; together with heparin, the proportion of compound (I) in mgs. to heparin in international Units being 1:5000. The composition may be in unit dosage form containing 0.5 mgs. of the alkaloid and 2,500 I.U. of heparin, together with a pharmaceutical carrier or diluent for injection (eg. poly-N- vinyl-2-pyrrolidone).
Description
This invention relates to new pharmaceutical compositions containing compounds of formula I, in which R is methyl or isopropyl is methyl R2 is isopropyl or benzyl and X- i s hydrogen with the proviso that R and Rg are not both isopropyl.
Belgian Patent 849010, the contents of which are incoporated herein by reference, discloses pharmaceutical compositions comprising a mixture of a compound of formula I and heparin, the proportions of compound of formula I (in mg) to heparin (in international units, I.U.) being from 1:500 to 1:70,000. The only mixtures which are specifically exempli fied, however, have a ratio of compound of formula I to heparin of 1:10,000; and are given as a unit dosage of 0.5 mg compound of formula I and 5000 I.U. heparin. The compositions are useful in the prophylaxis of thrombosis/particularly post-operative thrombosis, in mammals.
It has now been surprisingly found that a particularly useful combination is that having a ratio of compound of formula I to heparin of 1:5000, and a unit dosage of 0.5 mg compound of formula I and 2500 I.U. heparin.
By the use of this novel dosage, the advantageous antithrombotic effect is retained whereas side-effects associated with the use of heparin are reduced.
Accordingly, the invention provides a pharmaceutical composition comprising a mixture of a compound of formula I and heparin, in association with a pharmacologically acceptable diluent or carrier, the proportion of compound of formula I (in mg) to heparin (in I.U.) being 1:5000.
Preferably the compound of formula I is dihydroergotamine .
By the terms compounds of formula I and heparin" are included pharmacologically acceptable salts of these compounds. A pharmacologically acceptable salt is one which does not have substantially higher toxicity than the corresponding free acid or base. Examples of such salts are the methanesulfonate, maleate and tartrate salts of compounds of formula I, and the sodium, potassium and calcium salts of heparin.
A preferred diluent or carrier is uncrosslinked polyN-vinyl-2-pyrrolidone of average molecular weight from 2000 to 100,000, preferably from 2000 to 40,000.
The compositions may be prepared, tested and administered as disclosed in the above Belgian Patent.
A suitable indicated daily dosage is from 1 to 2 mg of compound of formula I and from 5000 to 10,000 I.U. heparin, preferably in the form of divided dosages of 0.5 mg compound of formula I and 2500 I.U. heparin 2 to 4 times daily.
All ratios given above are calculated on the basis that the compound of formula I is in free base form.
The following Examples illustrate the invention. 4-819 2 - 4 EXAMPLE 1: Dry mixture to make up injectable solution Dihydroergotamine methanesulfonate (4.6 g, corresponding to 4.0 g free base) and 476 g polyvinyl pyrrolidone (average MW 2000) is added to 1600 ml methanol in a 4 1 flask. The flask is connected to a rotary evaporator, and rotated in a bath at 60°C until the flask contents reach approximately 60°C. A clear solution is obtained.
The solvent is then evaporated under reduced pressure (ca. 250 Torr) at a bath temperature of 60°C, until the residue in the flask has a syrupy consistency. The residue is transferred to an evaporating dish and left to stand for two hours at room temperature. The solid residue is dried in a vacuum oven at 30°C, ca. 1 Torr for 12 hours, then milled and redried.
The dried residue (480 g) is then mixed under aseptic conditions with a quantity of sodium heparin corresponding to 20,000,000 I.V., 8 g disodium hydrogen phosphate dihydrate and 72 g sodium chloride, specially purified. The mixture is then made up in bottles of unit dosage sealed with a pierceable septum, each bottle containing 90 mg of the dry mixture, comprising 0.5 mg dihydroergotamine (as methanesulfonate) and 2500 I.V. sodium heparin.
In use, the septum is pierced by the needle of a syringe containing 1 ml of sterile distilled water which is injected into the bottle. When the solid mixture has dissolved, the solution is withdrawn into the syringe and administered parenterally.
EXAMPLE 2: Suspension Dihydroergotamine methanesulfonate (0.57 mg,corresponding to 0.5 mg free base) and a quantity of sodium heparin corresponding to 2,500,000 I.U. are dispersed in 1 1 of sterile filtered isopropyl myristate by stirring under aseptic conditions. Ampoules of 1 ml capacity are then filled with the suspension.
EXAMPLE 3: Freeze dried mixture to make up injectable solution a) A quantity of sodium heparin corresponding to 2,500,000 I.U., together with disodium hydrogen phospate (1 g) and sodium chloride (9 g) is dissolved in 500 ml of water suitable for injection. b) Dihydroergotamine methanesulfonate (0.57 g,corres15 ponding to 0.5 g free base) and polyvinylpyrrolidone (59.5 g) are dissolved in 500 ml of water suitable for injection. c) The solutions prepared according to a) and b) are mixed together and sterile filtered. The filtrate is used to fill ampoules under sterile conditions, each ampoule contain20 ing 1 ml of the combined solution. The unsealed ampoules are then subjected to freeze drying until all the water is removed. Finally the ampoules are sealed with a pierceable septum as in Example 1.
EXAMPLES 4, 5, 6: Examples 1, 2 and 3 are repeated using in place of dihydroergotamine methanesulfonate an equivalent quantity of 6-nor-6-isopropyl-9,10-dihydro-2'0-methyl-5-a-benzylergopeptin methanesulfonate. 8 19 2 EXAMPLES 7, 8, 9: Examples 1, 2 and 3 are repeated using instead of dihydroergotamine methanesulfonate an equivalent quantity of dihydroergovaline methanesulfonate.
Claims (7)
1. A pharmaceutical composition comprising a mixture of a compound of formula I !-R II C-NH—· O H «j HN- 1 in which R is methyl or isopropyl R^ is methyl R 2 is isopropyl or benzyl and X is hydrogen with the proviso that R and R 2 are not both isopropyl, and heparin, in association with a pharmaceutically acceptable diluent or carrier, the proportion of compound of formula I (in mg) to heparin (in International Units) being 1:5000.
2. A pharmaceutical composition as claimed in Claim 1, in which the compound of formula I is dihydroergotamine.
3. A pharmaceutical composition as claimed in Claim 1 or Claim 2, in which the pharmacologically acceptable diluent or carrier is uncrosslinked poly-N-vinyl-2-pyrrolidone of average molecular weight from 2000 to 100,000. 40192 - 8 j
4. A pharmaceutical composition as claimed in Claim 3 in which the polyvinylpyrrolidone has an average molecular weight of from 2000 to 40,000.
5. A pharmaceutical composition as claimed in any one 5 of the preceding claims, in unit dosage form, containing 0.5 mg of compound of formula I and 2500 I.U. heparin per unit.
6. A pharmaceutical composition as claimed in Claim 1, substantially as herein described with reference to any one
7. 10 of the Examples.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782809618 DE2809618A1 (en) | 1978-03-06 | 1978-03-06 | NEW THERAPEUTIC PREPARATION AND METHOD FOR THE PRODUCTION THEREOF |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE790701L IE790701L (en) | 1979-09-06 |
| IE48192B1 true IE48192B1 (en) | 1984-10-31 |
Family
ID=6033695
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE701/79A IE48192B1 (en) | 1978-03-06 | 1979-08-08 | Pharmaceutical compositions containing an ergot alkaloid and heparin |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS54126736A (en) |
| BE (1) | BE874626R (en) |
| CH (1) | CH639271A5 (en) |
| CY (1) | CY1298A (en) |
| DE (1) | DE2809618A1 (en) |
| FR (1) | FR2419070A2 (en) |
| GB (1) | GB2015338B (en) |
| HK (1) | HK81085A (en) |
| IE (1) | IE48192B1 (en) |
| KE (1) | KE3548A (en) |
| NL (1) | NL7901702A (en) |
| NZ (1) | NZ189817A (en) |
| PH (1) | PH16800A (en) |
| SG (1) | SG49185G (en) |
| ZA (1) | ZA791032B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2945636A1 (en) * | 1979-11-12 | 1981-05-21 | Sandoz-Patent-GmbH, 7850 Lörrach | STABLE SOLUTIONS OF HYDRATED ERGOTAL CALOIDS OR YOUR SALTS AND HEPARIN OR ITS SALTS AND METHOD FOR THE PRODUCTION THEREOF |
| CH656533A5 (en) * | 1982-12-10 | 1986-07-15 | Sandoz Ag | THERAPEUTIC PREPARATION CONTAINING HYDRATED ERGOTAL CALOIDS AND LOW MOLECULAR HEPARINE. |
| DE3343818A1 (en) * | 1982-12-10 | 1984-06-14 | Sandoz-Patent-GmbH, 7850 Lörrach | Therapeutic product containing hydrogenated ergot alkaloids and heparin |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE441142B (en) * | 1975-12-04 | 1985-09-16 | Sandoz Ag | PROCEDURE FOR PREPARING A THERAPEUTIC PREPARATION WITH ANTITHROMOBOTIC PROPERTIES |
-
1978
- 1978-03-06 DE DE19782809618 patent/DE2809618A1/en not_active Withdrawn
-
1979
- 1979-02-23 CH CH184079A patent/CH639271A5/en not_active IP Right Cessation
- 1979-03-02 GB GB7907393A patent/GB2015338B/en not_active Expired
- 1979-03-02 PH PH22245A patent/PH16800A/en unknown
- 1979-03-02 NL NL7901702A patent/NL7901702A/en not_active Application Discontinuation
- 1979-03-02 CY CY1298A patent/CY1298A/en unknown
- 1979-03-05 NZ NZ789817A patent/NZ189817A/en unknown
- 1979-03-05 JP JP2460879A patent/JPS54126736A/en active Pending
- 1979-03-05 BE BE0/193847A patent/BE874626R/en not_active IP Right Cessation
- 1979-03-06 FR FR7905752A patent/FR2419070A2/en active Granted
- 1979-03-06 ZA ZA791032A patent/ZA791032B/en unknown
- 1979-08-08 IE IE701/79A patent/IE48192B1/en unknown
-
1985
- 1985-06-24 SG SG49185A patent/SG49185G/en unknown
- 1985-07-11 KE KE3548A patent/KE3548A/en unknown
- 1985-10-17 HK HK810/85A patent/HK81085A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK81085A (en) | 1985-10-25 |
| KE3548A (en) | 1985-08-02 |
| GB2015338A (en) | 1979-09-12 |
| JPS54126736A (en) | 1979-10-02 |
| BE874626R (en) | 1979-09-05 |
| FR2419070A2 (en) | 1979-10-05 |
| SG49185G (en) | 1986-01-17 |
| CY1298A (en) | 1985-10-18 |
| GB2015338B (en) | 1982-08-18 |
| PH16800A (en) | 1984-03-01 |
| DE2809618A1 (en) | 1979-09-20 |
| NZ189817A (en) | 1981-04-24 |
| FR2419070B1 (en) | 1982-08-06 |
| CH639271A5 (en) | 1983-11-15 |
| ZA791032B (en) | 1980-10-29 |
| IE790701L (en) | 1979-09-06 |
| NL7901702A (en) | 1979-09-10 |
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