WO1996001634B1 - Long-acting oxytetracycline composition - Google Patents
Long-acting oxytetracycline compositionInfo
- Publication number
- WO1996001634B1 WO1996001634B1 PCT/GB1995/001583 GB9501583W WO9601634B1 WO 1996001634 B1 WO1996001634 B1 WO 1996001634B1 GB 9501583 W GB9501583 W GB 9501583W WO 9601634 B1 WO9601634 B1 WO 9601634B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- amount
- composition
- magnesium
- composition according
- oxytetracycline
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract 15
- 229960000625 Oxytetracycline Drugs 0.000 title claims 4
- 239000004100 Oxytetracycline Substances 0.000 title claims 4
- 235000019366 oxytetracycline Nutrition 0.000 title claims 4
- IWVCMVBTMGNXQD-PXOLEDIWSA-N Oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract 6
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract 5
- 229940074076 glycerol formal Drugs 0.000 claims abstract 5
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract 5
- 150000002681 magnesium compounds Chemical class 0.000 claims abstract 4
- 229960002180 Tetracycline Drugs 0.000 claims abstract 3
- 239000004098 Tetracycline Substances 0.000 claims abstract 3
- 239000007972 injectable composition Substances 0.000 claims abstract 3
- SECXISVLQFMRJM-UHFFFAOYSA-N n-methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims abstract 3
- 239000002904 solvent Substances 0.000 claims abstract 3
- 235000019364 tetracycline Nutrition 0.000 claims abstract 3
- -1 tetracycline compound Chemical class 0.000 claims abstract 3
- 239000002253 acid Substances 0.000 claims abstract 2
- 239000012458 free base Substances 0.000 claims abstract 2
- 239000007924 injection Substances 0.000 claims abstract 2
- 239000003002 pH adjusting agent Substances 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims abstract 2
- 239000011780 sodium chloride Substances 0.000 claims abstract 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims 6
- OWFJMIVZYSDULZ-PXOLEDIWSA-N (4S,4aR,5S,5aR,6S,12aR)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O OWFJMIVZYSDULZ-PXOLEDIWSA-N 0.000 claims 4
- 239000000395 magnesium oxide Substances 0.000 claims 3
- 241001465754 Metazoa Species 0.000 claims 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L MgCl2 Chemical group [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims 2
- 230000003078 antioxidant Effects 0.000 claims 2
- 239000003963 antioxidant agent Substances 0.000 claims 2
- 159000000003 magnesium salts Chemical class 0.000 claims 2
- VYGBQXDNOUHIBZ-UHFFFAOYSA-L sodium formaldehyde sulphoxylate Chemical compound [Na+].[Na+].O=C.[O-]S[O-] VYGBQXDNOUHIBZ-UHFFFAOYSA-L 0.000 claims 2
- IMLJLCJZQLGHJS-JEKSYDDFSA-N (4S,4aR,5S,5aR,6S,12aR)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;dihydrate Chemical compound O.O.C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O IMLJLCJZQLGHJS-JEKSYDDFSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 229960003924 Oxytetracycline Dihydrate Drugs 0.000 claims 1
- 230000037396 body weight Effects 0.000 claims 1
- 239000008139 complexing agent Substances 0.000 claims 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N ethanolamine Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 229910001629 magnesium chloride Inorganic materials 0.000 claims 1
- 239000012046 mixed solvent Substances 0.000 claims 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 239000002562 thickening agent Substances 0.000 claims 1
- 230000022534 cell killing Effects 0.000 abstract 1
- 230000009089 cytolysis Effects 0.000 abstract 1
- 230000001627 detrimental Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000002347 injection Methods 0.000 abstract 1
- 230000017074 necrotic cell death Effects 0.000 abstract 1
- 230000002522 swelling Effects 0.000 abstract 1
- 210000001519 tissues Anatomy 0.000 abstract 1
Abstract
An injectable composition of higher residual effect with reduced detrimental effects such as pain at injection site, swelling, tissue irritancy or necrosis and containing as active principle a tetracycline compound, either as the free base or a salt thereof with a physiologically acceptable acid, complexed with a substantially equimolar amount of a magnesium compound, is solubilised in a water miscible solvent system comprising, either (i) a) glycerol formal in an amount of from about 10 to about 50 % v/v; with b) polyethylene glycol in an amount of from about 1 to 15 % v/v; or (ii) from about 25 to about 75 % v/v of N-methylpyrrolidone, said composition optionally containing a pH modifier in an amount sufficient to maintain a physiochemically acceptable pH, the balance being made up with water q.s.
Claims
1. A composition containing as active principle a tetracycline compound, either as the free base or a salt thereof with a physiologically acceptable acid, complexed with a substantially equimolar amount of a magnesium compound, solubilised in a water miscible solvent system comprising, a) glycerol formal in an amount of from about 10 to about 50% v/v; with b) polyethylene glycol in an amount of from about 1 to 15% v/v; said composition optionally containing a pH modifier in an amount sufficient to maintain a physiochemically acceptable pH, the balance being made up with water q.s.
2. A composition according to claim 1 comprising as a thickener polyvinyl pyrrolidone in an amount of up to about 10% w/v.
3. A composition according to claim 1 or claim 2 wherein the magnesium compound is magnesium oxide.
4. A composition according to claim 1 or claim 2 wherein the magnesium compound is a magnesium salt.
5. A composition according to claim 4 wherein the magnesium salt is magnesium chloride.
6. A composition according to claim 1 wherein the tetracycline compound is oxytetracycline base or its hydrochloride in an amount of from about 15 to about 35% w/v.
7. A composition according to claim 1 wherein the composition contains about 30% w/v oxytetracycline, about
40% glycerol formal, about 10% v/v poly-ethylene glycol with a magnesium-containing complexing agent or stabiliser, antioxidant and water making up the balance.
8. A composition according to claim 7 wherein magnesium oxide is present in an amount of about 2.7% w/v and, as antioxidant, sodium formaldehyde sulphoxylate in an amount of about 0.4% w/v may be used.
9. An injectable composition for treatment of animals which consists of :
Oxytetracycline 300 mg Magnesium oxide 27 mg
Sodium formaldehyde sulphoxylate 4 mg Glycerol formal 0.4 ml
Polyethylene glycol 0.1 ml
Monoethanolamine q.s. pH 8.6 to 8.8 Water for injections to 1 ml, the said composition providing for administration of from about 10 to about 40 mg of oxytetracycline per kilogram of bodyweight .
10. An injectable composition for treatment of animals according to any one of the Examples 1 to 10 hereinbefore.
STATEMENT UNDER ARTICLE 19
The references EP-A-0 096 942, and US-A-4 772 460, both of which describe use of N-methylpyrrolidone as solvent in injectable solutions of oxytetracycline dihydrate at 20% w/v and suggest other strengths are possible, have been considered in revising claim 1 to remove references to use of N-methylpyrrolidone. Claim 10 has been amended for the same reasons. These references and those others cited in the search report have no impact on the resulting amended claims to formulations uniquely based on a glycerol formal - polyethylene glycol mixed solvent system which provides unexpectedly long-acting formulations (up to 9 days) .
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP50417996A JP4025925B2 (en) | 1994-07-09 | 1995-07-05 | Long acting oxytetracycline composition |
| CA002194576A CA2194576C (en) | 1994-07-09 | 1995-07-05 | Long-acting oxytetracycline composition |
| NZ288717A NZ288717A (en) | 1994-07-09 | 1995-07-05 | Long-acting tetracycline medicaments formed from tetracycline complexed with a magnesium compound and solubilised in a mixture of glycerol formal and polyethylene glycol |
| DE69531736T DE69531736T2 (en) | 1994-07-09 | 1995-07-05 | OXYTETRACYCLIN CONTAINING MEDICINE WITH DELAYED DELIVERY OF ACTIVE SUBSTANCE |
| EP95923502A EP0769951B1 (en) | 1994-07-09 | 1995-07-05 | Long-acting oxytetracycline composition |
| DK95923502T DK0769951T3 (en) | 1994-07-09 | 1995-07-05 | Long-acting oxytetracycline preparation |
| AT95923502T ATE249224T1 (en) | 1994-07-09 | 1995-07-05 | DELAYED RELEASE MEDICINAL PRODUCT CONTAINING OXYTETRACYCLINE |
| AU28043/95A AU707366B2 (en) | 1994-07-09 | 1995-07-05 | Long-acting oxytetracycline composition |
| US09/617,795 US6310053B1 (en) | 1995-07-05 | 2000-07-17 | Long-acting oxytetracycline composition |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9413873A GB9413873D0 (en) | 1994-07-09 | 1994-07-09 | Long-acting oxytetracycline composition |
| GB9413873.2 | 1994-07-09 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US76547597A Continuation | 1994-07-09 | 1997-04-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1996001634A1 WO1996001634A1 (en) | 1996-01-25 |
| WO1996001634B1 true WO1996001634B1 (en) | 1996-02-15 |
Family
ID=10758078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1995/001583 WO1996001634A1 (en) | 1994-07-09 | 1995-07-05 | Long-acting oxytetracycline composition |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0769951B1 (en) |
| JP (2) | JP4025925B2 (en) |
| CN (1) | CN1081461C (en) |
| AT (1) | ATE249224T1 (en) |
| AU (1) | AU707366B2 (en) |
| DE (1) | DE69531736T2 (en) |
| DK (1) | DK0769951T3 (en) |
| ES (1) | ES2204958T3 (en) |
| GB (1) | GB9413873D0 (en) |
| MX (1) | MX9700287A (en) |
| NZ (1) | NZ288717A (en) |
| PT (1) | PT769951E (en) |
| WO (1) | WO1996001634A1 (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2130069B1 (en) * | 1997-04-10 | 2000-03-01 | Basf Labiana S A | PHARMACEUTICAL PREPARATION WITH DELAYED RELEASE OF THE ACTIVE PRODUCT. |
| US6479473B1 (en) * | 1997-05-06 | 2002-11-12 | Norbrook Laboratories Ltd. | Long-acting antimicrobials |
| US6239112B1 (en) * | 1998-07-09 | 2001-05-29 | Merial, Inc. | Water miscible macrolide solutions |
| GB9928343D0 (en) * | 1999-11-30 | 2000-01-26 | Vericore Ltd | Addition of tetracyclines to animal foodstuffs |
| US6428975B1 (en) | 2000-01-14 | 2002-08-06 | Blue Ridge Pharmaceuticals, Inc. | Methods for determining the presence or absence of microorganisms in lipid-containing compositions |
| NO20014746D0 (en) | 2001-09-28 | 2001-09-28 | Clas M Kjoelberg | Pain reliever |
| ES2315123B1 (en) * | 2006-09-25 | 2009-12-30 | Divasa-Farmavic, S.A. | STABLE PHARMACEUTICAL COMPOSITIONS OF TETRACICLINES IN SOLUTION, PROCEDURE FOR OBTAINING AND USES. |
| ES2613738T3 (en) | 2010-05-12 | 2017-05-25 | Rempex Pharmaceuticals, Inc. | Tetracycline compositions |
| CN103271238B (en) * | 2013-05-10 | 2014-04-02 | 中国科学院亚热带农业生态研究所 | Preparation method of feed additive mono ethanol amine and application |
| CN106309357A (en) * | 2016-11-08 | 2017-01-11 | 河南益华动物药业有限公司 | Oxytetracycline hydrochloride gel implant for livestock and preparation method thereof |
| CN110693826A (en) * | 2019-11-18 | 2020-01-17 | 成都新亨药业有限公司 | Long-acting oxytetracycline injection for livestock and preparation method thereof |
| CN111035614B (en) * | 2019-12-20 | 2024-02-02 | 北京喜禽药业有限公司 | High-content terramycin injection and preparation method thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2034890B1 (en) * | 1969-03-13 | 1974-05-24 | Diamond Shamrock Corp | |
| DE2001604C2 (en) * | 1970-01-15 | 1983-04-14 | Pfizer Gmbh, 7500 Karlsruhe | Use of polyethylene glycol for the production of oxytetracycline solutions for parenteral, peroral and local application |
| US4259331A (en) * | 1979-04-16 | 1981-03-31 | Pfizer Inc. | Oxytetracycline compositions |
| CA1163197A (en) * | 1980-04-10 | 1984-03-06 | Herman Horn | Injectable oxytetracycline compositions |
| NL178941C (en) * | 1982-06-15 | 1986-06-16 | Aesculaap Bv | PROCESS FOR PREPARING AN AQUEOUS OXYTETRACYCLINE PREPARATION. |
| IE74244B1 (en) * | 1985-10-01 | 1997-07-16 | Bimeda Res Dev Ltd | A process for preparing an antibiotic composition |
| US5075295A (en) * | 1989-12-12 | 1991-12-24 | Boehringer Ingelheim Animal Health, Inc. | Novel oxytetracycline compositions |
-
1994
- 1994-07-09 GB GB9413873A patent/GB9413873D0/en active Pending
-
1995
- 1995-07-05 EP EP95923502A patent/EP0769951B1/en not_active Expired - Lifetime
- 1995-07-05 JP JP50417996A patent/JP4025925B2/en not_active Expired - Lifetime
- 1995-07-05 ES ES95923502T patent/ES2204958T3/en not_active Expired - Lifetime
- 1995-07-05 AU AU28043/95A patent/AU707366B2/en not_active Expired
- 1995-07-05 DE DE69531736T patent/DE69531736T2/en not_active Expired - Lifetime
- 1995-07-05 NZ NZ288717A patent/NZ288717A/en not_active IP Right Cessation
- 1995-07-05 CN CN95194645A patent/CN1081461C/en not_active Expired - Fee Related
- 1995-07-05 DK DK95923502T patent/DK0769951T3/en active
- 1995-07-05 PT PT95923502T patent/PT769951E/en unknown
- 1995-07-05 AT AT95923502T patent/ATE249224T1/en active
- 1995-07-05 WO PCT/GB1995/001583 patent/WO1996001634A1/en active IP Right Grant
-
1997
- 1997-01-09 MX MX9700287A patent/MX9700287A/en active IP Right Grant
-
2007
- 2007-08-08 JP JP2007206510A patent/JP4804431B2/en not_active Expired - Fee Related
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