CN101683341A - Levobupivacaine and levisoprenaline contained frozen dry powder preparation for injection - Google Patents
Levobupivacaine and levisoprenaline contained frozen dry powder preparation for injection Download PDFInfo
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- CN101683341A CN101683341A CN200810222564A CN200810222564A CN101683341A CN 101683341 A CN101683341 A CN 101683341A CN 200810222564 A CN200810222564 A CN 200810222564A CN 200810222564 A CN200810222564 A CN 200810222564A CN 101683341 A CN101683341 A CN 101683341A
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- levisoprenaline
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Abstract
The invention relates to a levobupivacaine and levisoprenaline contained frozen dry powder preparation for injection, which takes the levobupivacaine and levisoprenaline as medical active constituentsand forms drug composite by mixing with acceptable accessories pharmaceutically. The preparation method is that: the levobupivacaine and levisoprenaline are taken as raw material, the accessories with specific kinds and proportion are added, the frozen dry powder preparation for intravenous injection is prepared and developed by adopting the illustrative technological measures; the levobupivacaine and levisoprenaline contained frozen dry powder preparation is used for treating serious difficulty in breathing, caused by bronchospasm, rapidly releasing anaphylactic shock caused by drugs and prolonging the action time of infiltration anesthesia medicines.
Description
Technical field
The present invention relates to a kind of freeze-dried powder that contains chirocaine and levisoprenaline, belong to the pharmaceutical technology field.
Background technology
Chirocaine is the amide-type local anesthetic.Propagation and the rate of rise that reduce action potential generation and the conduction of blocking nerve stimulation of local anesthetic by the threshold value that increases nerve electric stimulation, the nerve stimulation of slowing down.Usually, the carrying out of anesthesia forms relevant with conduction velocity with diameter, the myelin of nerve fiber.Clinically, the forfeiture of function of nervous system is 1 in proper order) pain sensation, 2) sense of heat, 3) sense of touch, 4) proprioception and topognosis, 5) skeletal muscle intensity.
Levisoprenaline is the beta receptor agonist, and β 1 and beta 2 receptor are all had powerful agonism, to several no effects of α receptor.Main effect: 1. act on the heart β1Shou Ti, heart contractility is strengthened, heart rate is accelerated, and conduction is quickened, and cardiac output and myocardial oxygen consumption increase.2. vasoactive smooth muscle beta 2 receptor makes the obvious diastole of skeletal muscle blood vessel, the also diastole in various degree of kidney, mesentery blood vessel and arteria coronaria, and the blood vessel total peripheral resistance reduces.Its cardiovascular effect causes systolic pressure to raise, and diastolic pressure reduces, and it is big that pulse pressure difference becomes.3. act in the bronchial smooth muscle beta 2 receptor, make bronchial smooth muscle loose.4. promote glycogen and steatolysis, increase and organize oxygen consumption.
Summary of the invention
The present invention relates to a kind of freeze-dried powder that contains chirocaine and levisoprenaline, it is to be active component with chirocaine and levisoprenaline or their salt, mixes the Pharmaceutical composition of formation with suitable pharmaceutic adjuvant.
The unit formulation consumption of wherein said chirocaine or its salt is every 10ml: 15-150mg, and the unit formulation consumption of levisoprenaline or its salt is every 10ml: 0.05-2mg.
Described suitable pharmaceutic adjuvant comprises pharmaceutical carrier, pH regulator agent, antioxidant, intercalating agent.
Described pharmaceutical carrier can be one or more in mannitol, glucose, sorbitol, sodium chloride, dextran, sucrose, lactose, gelatin hydrolysate, trehalose, nicotiamide, citric acid, citrate, pantothenic acid and salt thereof, agedoite, aminoacid and amino acid salts, cholate, glycyrrhizic acid and salt thereof, cyclodextrin and the derivant thereof.
Described pH regulator agent is the water solublity regulator, can be hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, hydrobromic acid, formic acid, propanoic acid, acetic acid, potassium acetate, sodium acetate, Ammonium Acetate, boric acid, lactic acid, sodium lactate, citric acid, disodium citrate, the citric acid trisodium, sodium citrate, water citric acid, Monopotassium citrate, natrium carbonicum calcinatum, sal soda, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, phosphate, dalcium biphosphate, calcium hydrogen phosphate, calcium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, maleic acid, succinic acid and salt, D-tartaric acid, sodium bitartrate, potassium hydrogen tartrate, sodium potassium tartrate tetrahydrate, Borax, boric acid, triethanolamine, potassium metaphosphate, Kurrol's salt, in the Polymeric sodium metaphosphate. one or more.
Described antioxidant can be sulfurous acid, sulphite, bisulfites, pyrosulfite, thiosulfate, thioglycerin, gallic acid and salt, caffeic acid and caffeiate, ferulic acid and ferulate, the tert-butyl group in the fragrant ether of light basic mattress, di-t-butyl Pyrogentisinic Acid, sodium glutamate, glycine, cysteine, methionine, L-leucine, L-isoleucine, L-tryptophan, L-lysine, L-methionine, ascorbic acid and the salt thereof one or more.
Described intercalating agent can be one or more in sodium ethylene diamine tetracetate, Ca-EDTA, the sodium ethylene diamine tetracetate calcium.
The preparation technology of freeze-dried powder of the present invention, comprise the steps: to take by weighing the chirocaine of recipe quantity and levisoprenaline or their salt and add the dissolving of injection water, make solution, add an amount of pharmaceutical carrier then, regulate pH value 3.0～9.5, add 0.005%～5% needle-use activated carbon by amount of preparation, stir 10～120min, adopting 0.22 μ m microporous filter membrane fine straining behind the filtering decarbonization, after the intermediate detection is qualified, sterile filling, lyophilization, take out behind the vacuum gland, jewelling lid labeling gets product.Wherein freeze-dry process is: medicinal liquid places freeze drying box, freezing 3～6 hours, makes temperature drop to-35～-75 ℃; Distilled 6～18 hours for the first time, temperature rises to about-5 ℃; Distilled 2～8 hours for the second time, temperature rises to 25～50 ℃, takes out behind the vacuum gland.
Freeze-dried powder of the present invention mainly is applicable to because of severe dyspnea due to the bronchospasm, and the anaphylactic shock that causes such as cushion also can be used for prolonging the action time of infiltration anesthesia medication rapidly.The sudden cardiac arrest that a variety of causes causes is carried out the main rescue medication of cardio-pulmonary resuscitation.
The specific embodiment
Embodiment 1
Prescription:
Preparation method:
The sodium sulfite, levobupivacaine hydrochloride, the sulphuric acid levisoprenaline that take by weighing recipe quantity add the dissolving of 80% water for injection, make solution, the mannitol that adds recipe quantity, regulate pH value 3.0～9.5, medicinal liquid is heated to about 60 ℃, add 0.1% needle-use activated carbon by amount of preparation, stir 30min, adopt 0.22 μ m microporous filter membrane fine straining behind the filtering decarbonization again, after the intermediate detection was qualified, sterile filling is (every bottle of theoretical amount 5ml) in the cillin bottle of 10ml, and medicinal liquid is placed freeze drying box, freezing 4 hours, temperature is dropped to about-45 ℃; Distilled 12 hours for the first time, temperature rises to about-5 ℃; Distilled 4 hours for the second time, temperature rises to 30 ℃, take out behind the vacuum gland, and Zha Gai, promptly.
Embodiment 2:
Prescription:
Preparation method:
Sodium thiosulfate, levobupivacaine hydrochloride, the sulphuric acid levisoprenaline that takes by weighing recipe quantity joins and is heated to about 60 ℃ of 80% water for injection dissolving, the dextran that adds recipe quantity again, regulate pH value 3.0～9.5, add 0.1% needle-use activated carbon by amount of preparation, insulated and stirred 30min, filter, take off charcoal, adopt 0.22 μ m microporous filter membrane fine straining again, after the intermediate detection was qualified, sterile filling is (every bottle of theoretical amount 2ml) in the cillin bottle of 5ml, and medicinal liquid is placed freeze drying box, freezing 3 hours, temperature is dropped to about-45 ℃; Distilled 8 hours for the first time, temperature rises to about-5 ℃; Distilled 4 hours for the second time, temperature rises to 30 ℃, take out behind the vacuum gland, and Zha Gai, promptly.
Embodiment 3:
Prescription:
Preparation method:
Take by weighing the levobupivacaine hydrochloride of recipe quantity, sulphuric acid levisoprenaline joins and is heated to about 60 ℃ of 80% water for injection dissolving, the glycine that adds recipe quantity again, sodium pyrosulfite, sodium ethylene diamine tetracetate calcium, regulate pH value 3.0～9.5 after the stirring and dissolving, add 0.1% needle-use activated carbon by amount of preparation, insulated and stirred 30min, filter, take off charcoal, adopt 0.22 μ m microporous filter membrane fine straining again, after the intermediate detection was qualified, sterile filling is (every bottle of theoretical amount 2ml) in the cillin bottle of 5ml, and medicinal liquid is placed freeze drying box, freezing 3 hours, temperature is dropped to about-45 ℃; Distilled 14～16 hours for the first time, temperature rises to about-5 ℃; Distilled 4～6 hours for the second time, temperature rises to 30 ℃, take out behind the vacuum gland, and Zha Gai, promptly.
Embodiment 4:
Prescription:
Preparation method:
Take by weighing the levobupivacaine hydrochloride of recipe quantity, sulphuric acid levisoprenaline joins and is heated to about 60 ℃ of 80% water for injection dissolving, the glucose that adds recipe quantity again, mannitol, vitamin C, sodium ethylene diamine tetracetate calcium, regulate pH value 3.0～9.5 with disodium citrate after the stirring and dissolving, add 0.2% needle-use activated carbon by amount of preparation, insulated and stirred 15min, filter, take off charcoal, adopt 0.22 μ m microporous filter membrane fine straining again, after the intermediate detection was qualified, sterile filling is (every bottle of theoretical amount 2ml) in the cillin bottle of 5ml, and medicinal liquid is placed freeze drying box, freezing 4 hours, temperature is dropped to about-45 ℃; Distilled 14～16 hours for the first time, temperature rises to about-5 ℃; Distilled 4～6 hours for the second time, temperature rises to 40 ℃, take out behind the vacuum gland, and Zha Gai, promptly.
Embodiment 5:
Prescription:
Preparation method:
Levobupivacaine hydrochloride, the sulphuric acid levisoprenaline that takes by weighing recipe quantity joins and is heated to about 60 ℃ of 80% water for injection dissolving, the citric acid, the sodium citrate that add recipe quantity again, measuring pH value after the stirring and dissolving is 3.0～9.5, add 0.1% needle-use activated carbon by amount of preparation, insulated and stirred 20～30min, filter, take off charcoal, adopt 0.22 μ m microporous filter membrane fine straining again, after the intermediate detection was qualified, sterile filling is (every bottle of theoretical amount 3ml) in the cillin bottle of 7ml, and medicinal liquid is placed freeze drying box, freezing 6 hours, temperature is dropped to about-50 ℃; Distilled 16～18 hours for the first time, temperature rises to about-6 ℃; Distilled 6 hours for the second time, temperature rises to 35 ℃, take out behind the vacuum gland, and Zha Gai, promptly.
Claims (10)
1. containing the freeze-dried powder of chirocaine and levisoprenaline, it is characterized in that, is to be active component with chirocaine and levisoprenaline or their salt, mixes the Pharmaceutical composition of formation with suitable pharmaceutic adjuvant.
2. the described freeze-dried powder of claim 1 is characterized in that, the unit formulation consumption of described chirocaine or its salt is every 10ml:15-150mg.
3. the described freeze-dried powder of claim 1 is characterized in that, the unit formulation consumption of described levisoprenaline or its salt is every 10ml:0.05-2mg.
4. the described freeze-dried powder of claim 1 is characterized in that, described suitable pharmaceutic adjuvant comprises pharmaceutical carrier, pH regulator agent, antioxidant, intercalating agent.
5. the described freeze-dried powder of claim 4, it is characterized in that described pharmaceutical carrier can be one or more in mannitol, glucose, sorbitol, sodium chloride, dextran, sucrose, lactose, gelatin hydrolysate, trehalose, nicotiamide, citric acid, citrate, pantothenic acid and salt thereof, agedoite, aminoacid and amino acid salts, cholate, glycyrrhizic acid and salt thereof, cyclodextrin and the derivant thereof.
6. the described freeze-dried powder of claim 4, it is characterized in that, described pH regulator agent is the water solublity regulator, can be hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, hydrobromic acid, formic acid, propanoic acid, acetic acid, potassium acetate, sodium acetate, Ammonium Acetate, boric acid, lactic acid, sodium lactate, citric acid, disodium citrate, the citric acid trisodium, sodium citrate, water citric acid, Monopotassium citrate, natrium carbonicum calcinatum, sal soda, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, phosphate, dalcium biphosphate, calcium hydrogen phosphate, calcium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, maleic acid, succinic acid and salt, D-tartaric acid, sodium bitartrate, potassium hydrogen tartrate, sodium potassium tartrate tetrahydrate, Borax, boric acid, triethanolamine, potassium metaphosphate, Kurrol's salt, in the Polymeric sodium metaphosphate. one or more.
7. the described freeze-dried powder of claim 4, it is characterized in that described antioxidant can be sulfurous acid, sulphite, bisulfites, pyrosulfite, thiosulfate, thioglycerin, gallic acid and salt, caffeic acid and caffeiate, ferulic acid and ferulate, the tert-butyl group in the fragrant ether of light basic mattress, di-t-butyl Pyrogentisinic Acid, sodium glutamate, glycine, cysteine, methionine, L-leucine, L-isoleucine, L-tryptophan, L-lysine, L-methionine, ascorbic acid and the salt thereof one or more.
8. the described freeze-dried powder of claim 4 is characterized in that, described intercalating agent can be one or more in sodium ethylene diamine tetracetate, Ca-EDTA, the sodium ethylene diamine tetracetate calcium.
9. the preparation technology of the described freeze-dried powder of claim 1, comprise the steps: to take by weighing the chirocaine of recipe quantity and levisoprenaline or their salt and add the dissolving of injection water, make solution, add an amount of pharmaceutical carrier then, regulate pH value 3.0～9.5, add 0.005%～5% needle-use activated carbon by amount of preparation, stir 10～120min, adopting 0.22 μ m microporous filter membrane fine straining behind the filtering decarbonization, after the intermediate detection is qualified, sterile filling, lyophilization, take out behind the vacuum gland, jewelling lid labeling gets product.
10. the preparation technology of the described freeze-dried powder of claim 9 is characterized in that, described freeze-dry process is: medicinal liquid places freeze drying box, freezing 3～6 hours, makes temperature drop to-35～-75 ℃; Distilled 6～18 hours for the first time, temperature rises to about-5 ℃; Distilled 2～8 hours for the second time, temperature rises to 25～50 ℃, takes out behind the vacuum gland.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810222564A CN101683341A (en) | 2008-09-22 | 2008-09-22 | Levobupivacaine and levisoprenaline contained frozen dry powder preparation for injection |
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| Application Number | Priority Date | Filing Date | Title |
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| CN200810222564A CN101683341A (en) | 2008-09-22 | 2008-09-22 | Levobupivacaine and levisoprenaline contained frozen dry powder preparation for injection |
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| CN101683341A true CN101683341A (en) | 2010-03-31 |
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| CN200810222564A Pending CN101683341A (en) | 2008-09-22 | 2008-09-22 | Levobupivacaine and levisoprenaline contained frozen dry powder preparation for injection |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525894A (en) * | 2012-01-04 | 2012-07-04 | 上海禾丰制药有限公司 | Isoproterenol hydrochloride injection and preparation process thereof |
| CN102525893A (en) * | 2012-01-04 | 2012-07-04 | 上海禾丰制药有限公司 | Phenylephrine hydrochloride injection and preparation process thereof |
| US20130123741A1 (en) * | 2011-11-14 | 2013-05-16 | Galenova Inc | Flexible sterile bag containing pharmaceutical products and diluant separately and method of making the same |
| CN112552191A (en) * | 2020-12-11 | 2021-03-26 | 郑州安图生物工程股份有限公司 | Catechol amine substance freeze-dried powder and preparation method thereof |
-
2008
- 2008-09-22 CN CN200810222564A patent/CN101683341A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130123741A1 (en) * | 2011-11-14 | 2013-05-16 | Galenova Inc | Flexible sterile bag containing pharmaceutical products and diluant separately and method of making the same |
| CN102525894A (en) * | 2012-01-04 | 2012-07-04 | 上海禾丰制药有限公司 | Isoproterenol hydrochloride injection and preparation process thereof |
| CN102525893A (en) * | 2012-01-04 | 2012-07-04 | 上海禾丰制药有限公司 | Phenylephrine hydrochloride injection and preparation process thereof |
| CN102525893B (en) * | 2012-01-04 | 2013-11-20 | 上海禾丰制药有限公司 | Phenylephrine hydrochloride injection and preparation process thereof |
| CN112552191A (en) * | 2020-12-11 | 2021-03-26 | 郑州安图生物工程股份有限公司 | Catechol amine substance freeze-dried powder and preparation method thereof |
| CN112552191B (en) * | 2020-12-11 | 2023-06-13 | 郑州安图生物工程股份有限公司 | Catecholamine substance freeze-dried powder and preparation method thereof |
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Open date: 20100331 |