CN104382933A - Long-acting compound terramycin injection for animals - Google Patents
Long-acting compound terramycin injection for animals Download PDFInfo
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- CN104382933A CN104382933A CN201410748912.7A CN201410748912A CN104382933A CN 104382933 A CN104382933 A CN 104382933A CN 201410748912 A CN201410748912 A CN 201410748912A CN 104382933 A CN104382933 A CN 104382933A
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- 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
- A61K31/65—Tetracyclines
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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- 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
- A61K31/60—Salicylic acid; Derivatives thereof
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- 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
- A61K47/02—Inorganic compounds
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- 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
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- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- 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
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- 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
- A61K9/08—Solutions
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- Animal Behavior & Ethology (AREA)
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- General Chemical & Material Sciences (AREA)
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Abstract
The invention discloses a long-acting compound terramycin injection for animals. Each 1000 ml of long-acting compound terramycin injection contains 190-250g of occrycetin, 400-450g of alpha-pyrrolidone, 300-350ml of N,N-dimethyl formamide, 35-50g of nicotinamide, 35-50g of sodium salicylate, 100-130g of magnesium chloride, 100-130g of hydroxymethanesulfinic acid sodium hydrosulfite and 4-7g of disodium edetate dehydrate. A pH conditioning agent adjusts the pH value to 8.0-9.0; injecting water is used to perform calibration until the constant volume is 1000 ml; the pH conditioning agent is ethanol amine. According to the long-acting compound terramycin injection for animals, the chelating temperature is low and within 30-60 DEG C, products is high in chelating degree and steady in quality, and can still keep the standard amber within 2-year period of validity; an extended agent is added, so that drug function is good and the acting time is long; the drug function keeps for 72 hours after the drug in a normal dosage is administrated, so that the inconvenience of repeated drug administration is solved, and thus the long-acting function is played.
Description
Technical field
The invention belongs to field of veterinary, relate to a kind of long-acting veterinary compound terramycin injection.
Background technology
Oxytetracycline is as antibiotic most popular in the animals such as poultry, it is the essential drug of poultry health care, be mainly used in respiratory tract, urinary tract and the gastrointestinal infection treatment that the various antibacterial of animal, mycoplasma, chlamydia etc. cause, also can be used for the three pin health cares of newborn animal.Import Ursocycline injection quality is better, drug effect is long, but market price is very high.Domestic Terramycin injection for veterinary use then unstable properties, easy to change, precipitation, lost efficacy, non-refractory, just easy blackening when meeting high temperature 50 ~ 60 DEG C, inefficacy.
Summary of the invention
The object of the invention is for the deficiencies in the prior art, provide a kind of and be not subject to temperatures involved, steady quality, good drug efficacy, long-acting veterinary compound terramycin injection.
The object of the present invention is achieved like this: a kind of long-acting veterinary compound terramycin injection, it is characterized in that: hydrochloric oxytetracycline 190-250 gram, ɑ-ketopyrrolidine 400-450 gram, N in the every 1000ml of long-acting veterinary compound terramycin injection, dinethylformamide 300-350ml, nicotiamide 35-50 gram, sodium salicylate 35-50 gram, magnesium chloride 100-130 gram, sodium formaldehyde sulfoxylate 100-130 gram, disodiumedetate 4-7 gram, pH adjusting agent adjust pH, to 8.0-9.0, is settled to 1000ml with water for injection.
As preferably, hydrochloric oxytetracycline 210-240 gram, ɑ-ketopyrrolidine 410-440 gram, N in the every 1000ml of long-acting veterinary compound terramycin injection, dinethylformamide 310-340ml, nicotiamide 40-50 gram, sodium salicylate 40-50 gram, magnesium chloride 110-130 gram, sodium formaldehyde sulfoxylate 110-130 gram, disodiumedetate 5-7 gram, pH adjusting agent adjust pH, to 8.0-9.0, is settled to 1000ml with water for injection.
Described pH adjusting agent is ethanolamine.
The preparation method of above-mentioned long-acting veterinary compound terramycin injection is carried out according to the following steps:
1) get appropriate water for injection, add magnesium chloride and disodiumedetate (EDTA-2Na) stirring and dissolving, then add nicotiamide and sodium salicylate stirring, stand-by, be No. 1 liquid.
2) get appropriate water for injection and dissolve sodium formaldehyde sulfoxylate, stand-by, be No. 2 liquid.
3) add ɑ-ketopyrrolidine and DMF with No. 1 liquid that step 1 obtains, stir, slowly add tetramycin hydrochloride, stirring and dissolving.
4) add No. 2 liquid that step 2 obtains in liquid in step 3, stir evenly.
5) pH value is regulated with the liquid that step 4 obtains by ethanolamine.
6) standardize solution, aseptic filtration, embedding.
Add nicotiamide and sodium salicylate stirring in described step 1, temperature controls at 40-60 DEG C.
Dissolve sodium formaldehyde sulfoxylate in described step 2, temperature controls at 50-70 DEG C.
Cool with cold water when adding tetramycin hydrochloride stirring and dissolving in described step 3.
In described step 3, the response time controls within 30 minutes; Inflated with nitrogen is protected, and prevents from being oxidized in process for preparation.
Adjust between pH value to 8.0-9.0 with ethanolamine in described step 5.
Above-mentioned veterinary compound terramycin injection, its applicable object is: various domestic animal, poultry or other economic animal or house pet etc.Its route of administration can be: intramuscular injection, subcutaneous injection, oral or other route of administration.Its color is the amber of standard, and pH value is between 8.0-9.0.
The invention has the beneficial effects as follows: the present invention is directed to current Ursocycline injection non-refractory, oxidizable, perishable shortcoming, provide and be not subject to temperatures involved, steady quality, good drug efficacy, long-acting veterinary compound terramycin injection, this injection uses ɑ-ketopyrrolidine and tetramycin hydrochloride complexation, extend drug effect, long action time, after normal dose single administration, duration of efficacy reaches 72 hours, solve the inconvenience of repetitively administered, thus play long-acting effect; Use nicotiamide, not only play the effect of stabilizing agent, also there is certain curative effect simultaneously; With the addition of sodium formaldehyde sulfoxylate, serve antioxidative effect, make this injection holding time long; The sodium salicylate added plays the effect of antipyretic, analgesia, cooling, antiinflammatory, can also hydrotropy; Use DMF to play the effect of hydrotropy, use magnesium chloride, EDTA-2Na as stabilizing agent.Injection formula of the present invention makes product chelating degree high, steady quality, and within 2 years effect duration of shelf-life, it is amber that its color still can maintain the standard, and duration of efficacy reaches 72 hours, plays long-acting.
Detailed description of the invention
Embodiment 1
Prepare the long-acting veterinary compound terramycin injection of the present invention in accordance with the following steps:
1) get appropriate water for injection, add 10g magnesium chloride and 0.4g EDTA-2Na, stirring and dissolving, then add nicotiamide 3.5g and sodium salicylate 3.5g, stir (if desired can heating for dissolving), temperature controls at 40-60 DEG C, stand-by, is No. 1 liquid.
2) get appropriate water for injection and dissolve 10g sodium formaldehyde sulfoxylate, (if desired can heating for dissolving) temperature controls at 50-70 DEG C, stand-by, is No. 2 liquid.
3) in No. 1 liquid, 40g ɑ-ketopyrrolidine and 30g N is added; dinethylformamide fully stirs; slowly add tetramycin hydrochloride 19g; stirring and dissolving; cool with cold water during stirring; response time should not long (control within 30 minutes), for preventing being oxidized in process for preparation, and can inflated with nitrogen protection.
4) add No. 2 liquid (sodium formaldehyde sulfoxylate solution) after the liquid in step 3 all dissolves to stir.
5) regulate between pH value to 8.0-9.0 with ethanolamine.
6) 100ml is settled to water for injection, aseptic filtration, embedding.Inflated with nitrogen is answered during medicinal liquid embedding, and should embedding is complete as early as possible, forbid to stall for time, because medicinal liquid also can make its oxidation stain in atmosphere.Should keep in Dark Place after medicinal liquid embedding.
Embodiment 2
Prepare the long-acting veterinary compound terramycin injection of the present invention in accordance with the following steps:
1) get appropriate water for injection, add 12g magnesium chloride and 0.6g EDTA-2Na, stirring and dissolving, then add nicotiamide 4.0g and sodium salicylate 4.5g, stir (if desired can heating for dissolving), temperature controls at 40-60 DEG C, stand-by, is No. 1 liquid.
2) get appropriate water for injection and dissolve 12g sodium formaldehyde sulfoxylate, (if desired can heating for dissolving) temperature controls at 50-70 DEG C, stand-by, is No. 2 liquid.
3) in No. 1 liquid, 43g ɑ-ketopyrrolidine and 33g N is added; dinethylformamide fully stirs; slowly add tetramycin hydrochloride 22g; stirring and dissolving; cool with cold water during stirring; response time should not long (control within 30 minutes), for preventing being oxidized in process for preparation, and can inflated with nitrogen protection.
4) add No. 2 liquid (sodium formaldehyde sulfoxylate solution) after the liquid in step 3 all dissolves to stir.
5) regulate between pH value to 8.0-9.0 with ethanolamine.
6) 100ml is settled to water for injection, aseptic filtration, embedding.Inflated with nitrogen is answered during medicinal liquid embedding, and should embedding is complete as early as possible, forbid to stall for time, because medicinal liquid also can make its oxidation stain in atmosphere.Should keep in Dark Place after medicinal liquid embedding.
Embodiment 3
Prepare the long-acting veterinary compound terramycin injection of the present invention in accordance with the following steps:
1) get appropriate water for injection, add 13g magnesium chloride and 0.7g EDTA-2Na, stirring and dissolving, then add nicotiamide 5.0g and sodium salicylate 5.0g, stir (if desired can heating for dissolving), temperature controls at 40-60 DEG C, stand-by, is No. 1 liquid.
2) get appropriate water for injection and dissolve 13g sodium formaldehyde sulfoxylate, (if desired can heating for dissolving) temperature controls at 50-70 DEG C, stand-by, is No. 2 liquid.
3) in No. 1 liquid, 45g ɑ-ketopyrrolidine and 35g N is added; dinethylformamide fully stirs; slowly add tetramycin hydrochloride 25g; stirring and dissolving; cool with cold water during stirring; response time should not long (control within 30 minutes), for preventing being oxidized in process for preparation, and can inflated with nitrogen protection.
4) add No. 2 liquid (sodium formaldehyde sulfoxylate solution) after the liquid in step 3 all dissolves to stir.
5) regulate between pH value to 8.0-9.0 with ethanolamine.
6) 100ml is settled to water for injection, aseptic filtration, embedding.Inflated with nitrogen is answered during medicinal liquid embedding, and should embedding is complete as early as possible, forbid to stall for time, because medicinal liquid also can make its oxidation stain in atmosphere.Should keep in Dark Place after medicinal liquid embedding.
The clinical test of pesticide effectiveness of embodiment 4
Get natural occurrence piglet 80, two groups are divided at random by body weight size, often organize 40, average weight 7.0 kilograms, respectively by per kilogram of body weight 0.25ml intramuscular injection injection of the present invention and certain company 20% YANSUAN TUMEISU ZHUSHEYE (in contrast), the one time cure rate of result the present invention and matched group is respectively 94% and 80%, and secondary cure rate is respectively 98% and 90%, illustrates that clinical drug effect of the present invention is better than matched group.
The stability test of embodiment 5 product
This product is stored in 45 DEG C of calorstat accelerated tests, excessively within one month, detect when producing and often, by observation and the detection of 6 months, find that product colour is without significant change, the relative amount of oxytetracycline declines and is only 1.5%, pH value, between 8.0-9.0, illustrates that compound oxytetracycline injection of the present invention is high temperature resistant, for shelf-stable.Embodiment 6 drug effect metabolic test
Get healthy test rabbit 15, average weight 2.5 kilograms, by per kilogram of body weight intramuscular injection this product 0.25ml, test Cor Leporis blood is adopted respectively at 2h, 4h, 8h, 16h, 32h, 48h, 60h, 72h, 84h after injection, oxytetracycline in determination test rabbit blood respectively, still can measure when 72h in every ml blood and contain 1.5ug oxytetracycline, still can oxytetracycline be detected when 84h, illustrate that drug effect of the present invention is more than 72h.
Claims (3)
1. a long-acting veterinary compound terramycin injection, it is characterized in that: hydrochloric oxytetracycline 190-250 gram, ɑ-ketopyrrolidine 400-450 gram, N in the every 1000ml of long-acting veterinary compound terramycin injection, dinethylformamide 300-350ml, nicotiamide 35-50 gram, sodium salicylate 35-50 gram, magnesium chloride 100-130 gram, sodium formaldehyde sulfoxylate 100-130 gram, disodiumedetate 4-7 gram, pH adjusting agent adjust pH, to 8.0-9.0, is settled to 1000ml with water for injection.
2. a kind of long-acting veterinary compound terramycin injection as claimed in claim 1, it is characterized in that: hydrochloric oxytetracycline 210-240 gram, ɑ-ketopyrrolidine 410-440 gram, N in the every 1000ml of long-acting veterinary compound terramycin injection, dinethylformamide 310-340ml, nicotiamide 40-50 gram, sodium salicylate 40-50 gram, magnesium chloride 110-130 gram, sodium formaldehyde sulfoxylate 110-130 gram, disodiumedetate 5-7 gram, pH adjusting agent adjust pH, to 8.0-9.0, is settled to 1000ml with water for injection.
3. a kind of long-acting veterinary compound terramycin injection as claimed in claim 1 or 2, is characterized in that: described pH adjusting agent is ethanolamine.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410748912.7A CN104382933B (en) | 2014-12-08 | 2014-12-08 | Long-acting veterinary compound terramycin injection |
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| CN201410748912.7A CN104382933B (en) | 2014-12-08 | 2014-12-08 | Long-acting veterinary compound terramycin injection |
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| CN104382933A true CN104382933A (en) | 2015-03-04 |
| CN104382933B CN104382933B (en) | 2018-01-02 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106727373A (en) * | 2016-12-21 | 2017-05-31 | 驻马店华中正大有限公司 | A kind of occrycetin chewable tablets for animals and preparation method thereof |
| CN107308107A (en) * | 2017-07-06 | 2017-11-03 | 山东中牧兽药有限公司 | A kind of vibramycin injection and preparation method thereof |
| CN108158984A (en) * | 2018-01-24 | 2018-06-15 | 江西博莱大药厂有限公司 | A kind of Terramycin injection for veterinary use and preparation method thereof |
| CN108653200A (en) * | 2017-03-27 | 2018-10-16 | 辽宁天鹏生物科技有限公司 | A kind of long-acting occrycetin injection and preparation method thereof |
| CN111888356A (en) * | 2020-09-01 | 2020-11-06 | 重庆布尔动物药业有限公司 | Application of isoquinoline alkaloid in preparation of drug-resistant hemolytic staphylococcus drug |
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| CN103284944A (en) * | 2013-05-22 | 2013-09-11 | 安徽天安动物药业有限公司 | Method for preparing long-acting terramycin injection by utilizing carbamide and sodium bisulfite in combined way |
| CN104161761A (en) * | 2013-09-02 | 2014-11-26 | 郑州后羿制药有限公司 | Compound terramycin injection and preparation method thereof |
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2014
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| CN1123664A (en) * | 1994-12-03 | 1996-06-05 | 北海市兽药厂 | Veterinary injection and its production |
| CN101062042A (en) * | 2007-05-22 | 2007-10-31 | 江西核工业天地和药业有限公司 | Compound vibramycin injection for animals and the preparing method thereof |
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| CN101653448A (en) * | 2009-09-24 | 2010-02-24 | 陈建波 | Veterinary compound terramycin injection and preparation method thereof |
| CN102228462A (en) * | 2011-05-13 | 2011-11-02 | 山东德州神牛药业有限公司 | Method for preparing veterinary oxytetracycline-artemisinin injection and clinical application of veterinary oxytetracycline-artemisinin injection |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106727373A (en) * | 2016-12-21 | 2017-05-31 | 驻马店华中正大有限公司 | A kind of occrycetin chewable tablets for animals and preparation method thereof |
| CN108653200A (en) * | 2017-03-27 | 2018-10-16 | 辽宁天鹏生物科技有限公司 | A kind of long-acting occrycetin injection and preparation method thereof |
| CN107308107A (en) * | 2017-07-06 | 2017-11-03 | 山东中牧兽药有限公司 | A kind of vibramycin injection and preparation method thereof |
| CN108158984A (en) * | 2018-01-24 | 2018-06-15 | 江西博莱大药厂有限公司 | A kind of Terramycin injection for veterinary use and preparation method thereof |
| CN111888356A (en) * | 2020-09-01 | 2020-11-06 | 重庆布尔动物药业有限公司 | Application of isoquinoline alkaloid in preparation of drug-resistant hemolytic staphylococcus drug |
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|---|---|
| CN104382933B (en) | 2018-01-02 |
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