IE42999B1 - Stable solutions of ergot alkaloids - Google Patents
Stable solutions of ergot alkaloidsInfo
- Publication number
- IE42999B1 IE42999B1 IE1138/76A IE113876A IE42999B1 IE 42999 B1 IE42999 B1 IE 42999B1 IE 1138/76 A IE1138/76 A IE 1138/76A IE 113876 A IE113876 A IE 113876A IE 42999 B1 IE42999 B1 IE 42999B1
- Authority
- IE
- Ireland
- Prior art keywords
- component
- solution
- carbon atoms
- weight
- mixture
- Prior art date
Links
- 229960003133 ergot alkaloid Drugs 0.000 title description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 27
- 229930013930 alkaloid Natural products 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- PBUNVLRHZGSROC-VTIMJTGVSA-N dihydro-alpha-ergocryptine 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)CC(C)C)C(C)C)=C3C2=CNC3=C1 PBUNVLRHZGSROC-VTIMJTGVSA-N 0.000 claims description 5
- SEALOBQTUQIVGU-QNIJNHAOSA-N dihydroergocornine 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(C)C)=C3C2=CNC3=C1 SEALOBQTUQIVGU-QNIJNHAOSA-N 0.000 claims description 5
- 229960004290 dihydroergocornine Drugs 0.000 claims description 5
- LIMAOLZSWRJOMG-HJPBWRTMSA-N dihydroergocristine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@H]1CN(C)[C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C(C)C)C1=CC=CC=C1 LIMAOLZSWRJOMG-HJPBWRTMSA-N 0.000 claims description 5
- 229960004318 dihydroergocristine Drugs 0.000 claims description 5
- 229960002032 dihydroergocryptine Drugs 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 3
- 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
- 239000011261 inert gas Substances 0.000 claims description 3
- 239000012298 atmosphere Substances 0.000 claims description 2
- 230000007717 exclusion Effects 0.000 claims description 2
- 239000003708 ampul Substances 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 abstract 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 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
- 239000011976 maleic acid Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229940095064 tartrate Drugs 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
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
Abstract
STABLE SOLUTIONS AND PROCESSES FOR THEIR PREPARATION Solutions of hydrogenated ergopeptide alkaloids in pharmacologically acceptable organic solvents have improved stability. Preferred solvents are alcohols, particularly mixtures of ethanol and propylene glyool.
Description
This invention relates to solutions of ergot alkaloids and their synthetic derivatives including their hydrogenated derivatives and salt forms thereof.
Solutions of such compounds in predominantly aqueous media have the iisadvantage that the concentration of the active species decreases on storage, for example because of oxidation reactions. For this reason it is normal iractice to pass inert gas through the solution during filling of the vessels in which the solution is to be sold, and to protect the contents from air, light and high temperatures.
It has now been found that solutions of certain ergot alkaloids have improved stability when pharmacologically acceptable organic solvents are used in place of aqueous media.
The present invention provides a stable hydrogenated ergopeptide alkaloid ;olution consisting essentially of (a) a hydrogenated ergopeptide alkaloid or a pharmaceutically acceptable icid addition salt thereof or mixture thereof, (b) a pharmacologically acceptable monofunctional alcohol having up to 18 :arbon atoms or mixture thereof, - 2 42999 [-:} a po’yfunctional alcohol having up to 6 hydroxy groups or a polymeric poly^unctional alcohol having a molecular weight of from 200 to 20,000 or mixture thereof, and id) up to 40% by weight of the solution of water, the weight ratio of component (b) to component (c) being 1:01 to 1:100.
Sy the term hydrogenated ergopeptide alkaloids is included hydrogenated natural or synthetic ergopeptide alkaloids, and also their salt forms. The expression consisting essentially of is to be interpreted as meaning that the compositions do not contain any pharmaceutically active species other than comconent (a).
The pharmacologically acceptable monofunctional alcohols having up tc iS carbon atoms preferably have up to 10 carbon atoms and most preferably up to 3 carbon atoms. An especially preferred solvent of this type is ethanol. The polyfunctiona! alcohols having up to 6 carbon atoms and up to 6 hydroxy groups preferably have 2 or 3 carbon atoms and 2 or 3 hydroxy groups.
Especially preferred are glycerol and propylene glycol. The polyfunctional alcohols may also be used in polymeric form, for example polyalkylene glycols, especially polyethylene glycol, polypropylene glycol or their copolymers, having a molecular weight from 200 to 20,000, preferably from 200 to 600. A particularly suitable polyalcohol is polyethylene glycol with a molecular weight of approximately 400.
The above mono- and polyfunctional alcohols are used according to the invention in the form of mixtures in which the monofunctional and the polyfunctional alcohol are present in a ratio of from 1:0.1 to 1:100 by weight, preferably in a ratio of from 1:1 to 1:4, more preferably of 1:2 by weight.
A mixture of ethanol and propylene glycol is particularly preferred.
The solutions may of course contain a mixture of several mono- and/or polyfunctional alcohols.
Furthermore, the compositions according to the invention may further '9 contain, as additional solvents, pharmacologically acceptable organic esters and ethers, particularly those formed from the above-mentioned mono- and polyfunctional alcohols and fatty acids having from 12-18 carbon atoms, for example stearic acid, palmitic acid and oleic acid; or fatty alcohols having from 12 to 18 carbon atoms, for example lauryl alcohol, cetyl alcohol and stearyl a1cohol.
The compositions may contain minor amounts of water, but the water content must not exceed 402 by weight of the composition.
Hydrogenated natural and synthetic ergopeptide alkaloids which may be stabilised in solution by the process of the invention include dihydroergotamine, dihydroergocristine, dihydroergocryptine, dihydroergocornine and nixtures thereof, particularly a mixture of dihydroergocristine, dihydroirgocryptine and dihydroergocornine in 1:1:1 ratio. Suitable salt forms are salts of pharmacologically acceptable acids, for example the methanesulphonate, naleate and tartrate.
Although the concentration of the hydrogenated ergopeptide alkaloids in the solutions is not critical, it is preferred to use solutions with a soncentration of active species of from 0.1 to 1% by weight, preferably from 3.1 to 0.52 by weight. It is to be understood that the concentration to be ised will depend upon the application for which the solution is intended.
The solutions may in addition contain further solubilising additives For example acids, particularly methanesulphonic acid, maleic acid and tartaric icid.
The preparation of the compositions according to the invention is :arried out by dissolving the hydrogenated ergopeptide alkaloids in one of the lescribed organic solvent mixtures by stirring, suitably under an atmosphere )f inert gas, e.g. nitrogen, and suitably with exclusion of daylight and at •oom temperature (15-25°C). - 4 42999 The preparation of solvent mixtures is carried out in conventional manner, ar.d where one cf the solvent components is solid at room temperature, mixing is suitably carried out at higher temperatures, e.g. at up to 80°C.
Ethanol may advantageously be used as co-solvent.
Compositions according to the invention are useful as pharmaceuticals in the same way as corresponding aqueous solutions of the same active species. They may be administered orally, and may for this purpose be made up in vessels aesicned to dispense unit dosages, for example dropper bottles; or parenteraily, in which case the solutions will normally be sterilized and may be sealed in ampoules of unit dosage, EXAMPLE 1.
A mixture of 50.0 g propylene glycol and 41.9 g 94% ethanol was prepared and in this mixture was dissolved, by stirring at room temperature under a nitrogen atmosphere, 0.1 g of a mixture of dihydroergocristine, dihydroergocryptine and dihydrcergocornine (1:1:1). After filtration under pressure, the solution was used to fill dropper bottles.
EXAMPLE 2.
A mixture of 40.0 g propylene glycol, 34.0 g 94% ethanol and 25.0 g anhydrous glycerol was prepared and in this mixture was dissolved, by stirring at room temperature under a nitrogen atmosphere, 0.1 g of a mixture of di hydroergocri stine, dihydroergocryptine and dihydroergocornine (1:1:1).
After filtration under pressure, the solution was used to fill dropper bottles.
EXAMPLE 3.
A mixture of 50.0 propylene glycol and 41.9 g 94% ethanol was prepared and in this mixture was dissolved, by stirring at room temperature under a nitrogen atmosphere, 0.1 g of dihydroergotamine methanesulphonate. After filtration under pressure, the solution was used to fill dropper bottles.
Claims (11)
1. A stable hydrogenated ergopeptide alkaloid solution consisting essentially of a) a hydrogenated ergopeptide alkaloid as herein defined, b) a pharmacologically acceptable monofunctional alcohol having up to 18 carbon atoms, c) a polyfunctional alcohol having up to 6 carbon atoms and 6 hydroxy groups or a polymeric polyfunctional alcohol having a molecular weight of from 200 to 20,000, and d) up to 40% by weight of the solution of water, the weight ratio of component b) to component c) being 1:0.1 to 1:100.
2. A solution as claimed in Claim 1 in which the concentration of component a) is from 0.1 to 1 per cent by weight.
3. A solution as claimed in Claim 2 in which the concentration of component a) is from 0.1 to 0.5 per cent by weight.
4. A solution as claimed in any one of Claims 1-3 in which component b) has up to 10 carbon atoms and the ratio of component b) to component c) is 1:1 to 1:10.
5. A solution as claimed in Claim 4 in which component b) has up to 3 carbon atoms and component c) is a polyhydroxy alcohol of 2 to 3 carbon atoms and 2 or 3 hydroxy groups or a polymeric polyhydroxy alcohol having a molecular weight of 200 to 600 and the ratio of component b) to component c) is 1:1 to 1:4.
6. A solution as claimed in Claim 5 in which the ratio of component b) to somponent c) is 1:1 to 1:2. 1. A solution as claimed in Claim 5 in which the ratio of component b) to :omponent c) is 1:2. 3. A solution as claimed in any one of the preceding claims in which :omponent a) is ethanol and component b) is propylene glycol or glycerol or a fixture thereof. - 6 42999
7. 9. A solution as claimed in any one of the preceding claims in which the hydrogenated ergopeptide alkaloid is dihydroergotamine, dihydroergocristine dihydroergocryptine, dihydroergocornine or pharmaceutically acceptable salts thereof or mixtures thereof. 5 10. A solution as claimed in Claim 9 in which the hydrogenated ergopeptide alkaloid is a 1:1:1 mixture of dihydroergocristine, dihydroergocryptine and dihydroergocornine or pharmaceutically acceptable salts thereof. 11. A sterilized, sealed ampoule containing essentially a solution as claimed in any one of the preceding claims.
8. 10 12. A dropper bottle containing essentially a solution as claimed in any one of the preceding claims.
9. 13. « method of preparing a stable hydrogenated ergopeptide alkaloid solution according to Claim 1 which comprises dissolving a hydrogenated ergopeptide alkaloid or a pharmaceutically acceptable acid addition salt
10. 15 thereof or mixture thereof in a solvent consisting essentially of: a) a pharmacologically acceptable monofunctional alcohol having up to 18 carbon atoms or mixture thereof; b) a polyfunctional alcohol having up to 6 carbon atoms arid 6 hydroxy groups or a polymeric polyfunctional alcohol having a molecular weight of from 200 to 20,000 or mixture thereof; and c) up to 40%
11. 20 by weight of the solution of water, the weight ratio of component b) to component c) being 1:0.1 to 1:100, under an atmosphere of inert gas with the exclusion of daylight and at a temperature of 15 to 25°C.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2524184 | 1975-05-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE42999L IE42999L (en) | 1976-11-30 |
| IE42999B1 true IE42999B1 (en) | 1980-12-03 |
Family
ID=5947910
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1138/76A IE42999B1 (en) | 1975-05-31 | 1976-05-28 | Stable solutions of ergot alkaloids |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS585167B2 (en) |
| AT (1) | AT355725B (en) |
| AU (1) | AU508625B2 (en) |
| BE (1) | BE842348A (en) |
| CA (1) | CA1069438A (en) |
| CS (1) | CS205023B2 (en) |
| DD (1) | DD125597A5 (en) |
| DK (1) | DK154606C (en) |
| ES (1) | ES448372A1 (en) |
| FI (1) | FI761461A (en) |
| FR (1) | FR2313059A1 (en) |
| GB (1) | GB1539083A (en) |
| GR (1) | GR60264B (en) |
| HK (1) | HK15383A (en) |
| HU (1) | HU171514B (en) |
| IE (1) | IE42999B1 (en) |
| IL (1) | IL49668A (en) |
| MY (1) | MY8300013A (en) |
| NL (1) | NL172616C (en) |
| NO (1) | NO145262C (en) |
| NZ (1) | NZ180984A (en) |
| PT (1) | PT65151B (en) |
| SE (1) | SE426782B (en) |
| SU (2) | SU677664A3 (en) |
| YU (1) | YU133076A (en) |
| ZA (1) | ZA763138B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2935515A1 (en) * | 1979-09-03 | 1981-03-19 | Fa. Dr. Willmar Schwabe, 7500 Karlsruhe | MEDICINAL PRODUCT |
| FR2483235A1 (en) * | 1980-05-28 | 1981-12-04 | Fabre Sa Pierre | TOPICAL COMPOSITIONS CONTAINING RYE AND VINCA ROSEA ERGOT ALKALOIDS FOR THE TREATMENT OF HYPERSEBORRHOES |
| DE3227122A1 (en) * | 1982-07-20 | 1984-01-26 | Dr. Rentschler Arzneimittel Gmbh & Co, 7958 Laupheim | STABLE SOLUTIONS OF MOTHER CORNAL CALOIDS |
| HU192050B (en) * | 1983-04-22 | 1987-05-28 | Sandoz Ag | Process for production of medical preparative containing co-dergocrin and one piridin-dicarbonic acid diesthertype calcium-antagonist |
| IT1200609B (en) * | 1985-04-04 | 1989-01-27 | Poli Ind Chimica Spa | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF CEREBROVASCULAR TURBES AND THE ELDERLY BRAIN |
| DE102007014947B4 (en) | 2007-03-23 | 2010-05-27 | Axxonis Pharma Ag | Stabilized aqueous solutions of ergoline compounds |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD43402A (en) * | ||||
| US2033921A (en) * | 1931-08-28 | 1936-03-17 | Squibb & Sons Inc | Solution of ergot alkaloids |
| US1969382A (en) * | 1932-05-21 | 1934-08-07 | Squibb & Sons Inc | Preparation of a stable hydro-alcoholic extract of ergot |
-
1976
- 1976-05-24 DK DK228676A patent/DK154606C/en not_active IP Right Cessation
- 1976-05-24 NO NO761760A patent/NO145262C/en unknown
- 1976-05-24 SE SE7605841A patent/SE426782B/en not_active IP Right Cessation
- 1976-05-24 FI FI761461A patent/FI761461A/fi not_active Application Discontinuation
- 1976-05-25 FR FR7615744A patent/FR2313059A1/en active Granted
- 1976-05-26 GB GB21809/76A patent/GB1539083A/en not_active Expired
- 1976-05-26 ZA ZA00763138A patent/ZA763138B/en unknown
- 1976-05-27 IL IL49668A patent/IL49668A/en unknown
- 1976-05-28 PT PT65151A patent/PT65151B/en unknown
- 1976-05-28 DD DD193077A patent/DD125597A5/xx unknown
- 1976-05-28 JP JP51062848A patent/JPS585167B2/en not_active Expired
- 1976-05-28 NL NLAANVRAGE7605745,A patent/NL172616C/en not_active IP Right Cessation
- 1976-05-28 IE IE1138/76A patent/IE42999B1/en unknown
- 1976-05-28 NZ NZ180984A patent/NZ180984A/en unknown
- 1976-05-28 AT AT390476A patent/AT355725B/en not_active IP Right Cessation
- 1976-05-28 AU AU14422/76A patent/AU508625B2/en not_active Expired
- 1976-05-28 CA CA253,612A patent/CA1069438A/en not_active Expired
- 1976-05-28 BE BE167442A patent/BE842348A/en not_active IP Right Cessation
- 1976-05-29 ES ES448372A patent/ES448372A1/en not_active Expired
- 1976-05-29 GR GR50841A patent/GR60264B/en unknown
- 1976-05-31 CS CS763620A patent/CS205023B2/en unknown
- 1976-05-31 SU SU762362650A patent/SU677664A3/en active
- 1976-05-31 HU HU76SA00002923A patent/HU171514B/en not_active IP Right Cessation
- 1976-05-31 SU SU762362650D patent/SU952106A3/en active
- 1976-05-31 YU YU01330/76A patent/YU133076A/en unknown
-
1983
- 1983-05-12 HK HK153/83A patent/HK15383A/en unknown
- 1983-12-30 MY MY13/83A patent/MY8300013A/en unknown
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