CN101254176A - Freeze-dried powder needle preparations taking dantrolene sodium as activity component and preparation technique thereof - Google Patents
Freeze-dried powder needle preparations taking dantrolene sodium as activity component and preparation technique thereof Download PDFInfo
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- CN101254176A CN101254176A CNA2008101008698A CN200810100869A CN101254176A CN 101254176 A CN101254176 A CN 101254176A CN A2008101008698 A CNA2008101008698 A CN A2008101008698A CN 200810100869 A CN200810100869 A CN 200810100869A CN 101254176 A CN101254176 A CN 101254176A
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Abstract
The invention relates to lyophilized powder for injection with dantrolene sodium as an active ingredient and a preparation method and uses thereof. The lyophilized powder is a pharmaceutical composition formed by mixing dantrolene sodium as the active ingredient and pharmaceutically-acceptable adjuvant, and is mainly suitable for spastic hypermyotonia state caused by upper motor neuron damage due to various reasons, such as apoplexy, cerebral trauma, spinal injury and multiple sclerosis. A lyophilized powder for intravenous injection can be prepared by using dantrolene sodium as a raw material and adding certain types and proportion of adjuvants according to the technical proposal given in the invention.
Description
Technical field
The present invention relates to a kind of is the freeze-dried powder and the preparation technology thereof of active component with the dantamacrin, belongs to medical technical field.
Background technology
Dantamacrin, its chemistry 1-{[5-(4-nitrobenzophenone) by name-2-furyl] methylene } amino-2,4-imidazolidimedione sodium salt 3.5 water of crystallization.
Its structural formula is as follows:
Dantamacrin is a kind of muscle relaxant that is directly used in skeletal muscle.The bubble slurry net that its main site of action is a skeletal muscle weakens muscle contraction by suppressing sarcoplasmic reticulum release calcium ion.Dantamacrin is different from general muscle relaxant, its unique mechanism is to directly act on skeletal muscle, suppress muscle contraction by suppressing sarcoplasmic reticulum release calcium ion, thereby can improve patient's motor skill, increase the joint initiatively with the scope of passive activity, alleviate the related symptoms of patient's dyskinesia, promote the recovery of function. mainly be applicable to upper motor neuron damage that a variety of causes causes in the spastic muscular hypertonia state left over, as apoplexy, cerebral trauma, spinal cord injury, cerebral palsy, multiple sclerosis etc., there are some researches show dantamacrin to apoplexy, cerebral palsy causes that the treatment obvious effective rate of muscle spasm is 96.77%, total effective rate 100%.Wherein reducing the muscular tension total effective rate is 87.10%, and reducing the tendon reflex total effective rate is 61.29%, and alleviating the myoclonus total effective rate is 83.87%.
The skeleton myotonic that also can be used for due to some other non-impairment factor of dantamacrin shrinks in addition, for example malignant hyperthermia, pernicious syndrome, and this class disease mostly is acute onset, and oral result is relatively poor.(Malignant Hyperthermia is known todayly uniquely can anaesthetize the hereditary that medication causes peri-operation period death by routine MH) to malignant hyperthermia.It is a kind of subclinical myonosus, it is the no abnormal at ordinary times performance of patient, occurring the skeleton myotonic in the general anesthesia process behind contact volatility inhalation anesthetic (as halothane, enflurane, isoflurane etc.) and the depolarizing relaxant (succinylcholine) shrinks, produce big energy, cause body temperature to increase continuously and healthily, general clinical cooling measure is difficult to control increasing of body temperature, finally can cause death.The present domestic specific medicine that also do not have.(neuroleptic malignant syndrom NMS) is the serious adverse of antipsychotic drug to pernicious syndrome.Mortality rate is up to 15%～20%, and the various ages all can be suffered from NMS, and male's number of the infected is higher than the women, and ratio is about 8: 3, when pilosity is born in and is begun to use height and tire antipsychotic drug.Part patient can have preceding body symptoms such as excitement is restless, refusing to eat, insomnia, dehydration, malnutrition.Acute onset, progress rapidly.The first symptom of case more than 80% is extrapyramidal symptoms and/or disturbance of consciousness, occurs other symptoms such as autonomic nerve symptom, hyperpyrexia, myotonia subsequently.
The dantamacrin of present domestic application is mainly capsule, and also there are certain limitation in its oral absorption speed and availability.
Summary of the invention
Having the purpose of this invention is to provide a kind of is the freeze-dried powder and uses thereof of active component with the dantamacrin.The present invention for a kind of be the Pharmaceutical composition of active component with the dantamacrin, it is characterized in that it is the active component that dantamacrin forms, the Pharmaceutical composition that forms with mixing acceptable accessories.
Described a kind of be the Pharmaceutical composition of active component with the dantamacrin, it is characterized in that, it is characterized in that described dantamacrin.Its unit dose scope is at 5 one 80mg.
Described a kind of be the Pharmaceutical composition of active component with the dantamacrin, it is characterized in that, it is characterized in that described suitable pharmaceutic adjuvant comprises pharmaceutical carrier, pH regulator agent, antioxidant (if necessary), intercalating agent (if necessary).
Above-mentioned a kind of be the Pharmaceutical composition of active component with the dantamacrin, 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.
Described a kind of be the Pharmaceutical composition of active component with the dantamacrin, 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, citric acid monohydrate, potassium 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 one 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 a kind of be the Pharmaceutical composition of active component with the dantamacrin, 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 one leucine, L one isoleucine, L one tryptophan, L one lysine, L one methionine, ascorbic acid and the salt thereof one or more.
Described a kind of be the Pharmaceutical composition of active component with the dantamacrin, it 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.
Described a kind of be the preparation technology of the lyophilized powder of active component with the dantamacrin, it is characterized in that, comprise the steps: that the dantamacrin that takes by weighing recipe quantity adds the dissolving of injection water, make hydrochloric acid Liolol solution, add an amount of pharmaceutical carrier, regulate pH value 8.0 1 12.0, add 0.005% one 5% needle-use activated carbons by amount of preparation, stir 10 1 120min, adopting 0.22 μ m microporous filter membrane fine straining behind the filtering decarbonization, after the intermediate detection is qualified, sterile filling, lyophilization is taken out behind the vacuum gland, and jewelling lid labeling gets product.
Described a kind of be the freeze-dry process of the lyophilized powder of active component with the dantamacrin, it is characterized in that described freeze-dry process is: medicinal liquid places freeze drying box, freezing 3 one 6 hours, makes temperature drop to-35 1-75 ℃; Distilled 6 one 18 hours for the first time, temperature rises to about-5 ℃; Distilled 2 one 8 hours for the second time, temperature rises to 25 1 50 ℃, takes out behind the vacuum gland.
Described a kind of be the freeze-dried powder of active component with the dantamacrin, mainly be applicable to upper motor neuron damage that a variety of causes causes in the spastic muscular hypertonia state left over, as apoplexy, cerebral trauma, spinal cord injury, cerebral palsy, multiple sclerosis etc.Can be used for the treatment of malignant hyperthermia, pernicious syndrome in addition.
The specific embodiment
Come dantamacrin freeze-dried powder of the present invention done further specifying by following example, but be not limited in following example.
Embodiment 1 dantamacrin freeze-dried powder
Prescription:
Preparation method:
The dantamacrin that takes by weighing recipe quantity adds the dissolving of 80% water for injection, makes dantamacrin solution, adds the mannitol of recipe quantity, regulate pH value 9.0 1 10.5, medicinal liquid is heated to about 60 ℃, adds 0.1% needle-use activated carbon, stir 30min by amount of preparation, 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 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 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: the dantamacrin freeze-dried powder
Prescription:
Preparation method:
The dantamacrin that takes by weighing recipe quantity joins and is heated to about 60 ℃ of 80% water for injection dissolving, adds the dextran of recipe quantity again, regulates pH value 9.0 1 10.5, add 0.1% needle-use activated carbon by amount of preparation, insulated and stirred 30min filters, and takes 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 1ml) in the cillin bottle of 2.7ml, 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: the dantamacrin freeze-dried powder
Prescription:
Preparation method:
The dantamacrin that takes by weighing recipe quantity joins and is heated to about 60 ℃ of 80% water for injection dissolving, the glycine, sodium pyrosulfite, the sodium ethylene diamine tetracetate calcium that add recipe quantity again, regulate pH value 9.0 1 10.5 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 hour for the first time, temperature rises to about-5 ℃; Distilled 4-6 hour for the second time, temperature rises to 30 ℃, take out behind the vacuum gland, and Zha Gai, promptly.
Embodiment 4: the dantamacrin freeze-dried powder
Prescription:
Preparation method:
The dantamacrin that takes by weighing recipe quantity joins and is heated to about 60 ℃ of 80% water for injection dissolving, the glucose, mannitol, vitamin C, the sodium ethylene diamine tetracetate calcium that add recipe quantity again, regulate pH value 9.0-10.5 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 hour for the first time, temperature rises to about-5 ℃; Distilled 4-6 hour for the second time, temperature rises to 40 ℃, take out behind the vacuum gland, and Zha Gai, promptly.
Embodiment 5: the dantamacrin freeze-dried powder
Prescription:
Preparation method:
The dantamacrin 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 9.0 1 10.5, 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 4ml) 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 hour 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. a dantamacrin freeze-dried powder is characterized in that containing dantamacrin and other suitable pharmaceutic adjuvant.
2. freeze-dried powder according to claim 1 is characterized in that described dantamacrin.Its unit dose scope is at 5-80mg.
3. freeze-dried powder according to claim 1 is characterized in that described suitable pharmaceutic adjuvant comprises pharmaceutical carrier, pH regulator agent, antioxidant (if necessary), intercalating agent (if necessary).
4. freeze-dried powder according to claim 3, 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.
5. freeze-dried powder according to claim 3, 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, citric acid monohydrate, 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 one 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.
6. freeze-dried powder according to claim 3, 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 one leucine, L one isoleucine, L one tryptophan, L one lysine, L one methionine, ascorbic acid and the salt thereof one or more.
7. freeze-dried powder according to claim 3 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.
8. the preparation technology of dantamacrin freeze-dried powder according to claim 1, comprise the steps: that the dantamacrin that takes by weighing recipe quantity adds the dissolving of injection water, make dantamacrin solution, add an amount of pharmaceutical carrier, regulate pH value 8.0 1 12.0, add 0.005% one 5% needle-use activated carbons by amount of preparation, stir 10 1 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.
9. the preparation technology of a kind of dantamacrin freeze-dried powder according to claim 1 is characterized in that, described freeze-dry process is: medicinal liquid places freeze drying box, freezing 3 one 6 hours, makes temperature drop to-35 1-75 ℃; Distilled 6 one 18 hours for the first time, temperature rises to about-5 ℃; Distilled 2 one 8 hours for the second time, temperature rises to 25 1 50 ℃, takes out behind the vacuum gland.
Claim 1 described a kind of be the freeze-dried powder of active component with the dantamacrin, mainly be applicable to upper motor neuron damage that a variety of causes causes in the spastic muscular hypertonia state left over, as apoplexy, cerebral trauma, spinal cord injury, cerebral palsy, multiple sclerosis etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101008698A CN101254176A (en) | 2008-02-25 | 2008-02-25 | Freeze-dried powder needle preparations taking dantrolene sodium as activity component and preparation technique thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101008698A CN101254176A (en) | 2008-02-25 | 2008-02-25 | Freeze-dried powder needle preparations taking dantrolene sodium as activity component and preparation technique thereof |
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| CN101254176A true CN101254176A (en) | 2008-09-03 |
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| CNA2008101008698A Pending CN101254176A (en) | 2008-02-25 | 2008-02-25 | Freeze-dried powder needle preparations taking dantrolene sodium as activity component and preparation technique thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302461A (en) * | 2011-09-02 | 2012-01-04 | 海南锦瑞制药股份有限公司 | Dantrolene sodium freeze-dried powder injection for injection and preparation method thereof |
| CN106413709A (en) * | 2013-12-05 | 2017-02-15 | 阿勒根公司 | Treatment of spasticity with intrathecal dantrolene |
| CN111419795A (en) * | 2020-05-09 | 2020-07-17 | 上药东英（江苏）药业有限公司 | Danqulin sodium suspension for injection and preparation method thereof |
| CN111825662A (en) * | 2019-04-18 | 2020-10-27 | 丽珠医药集团股份有限公司 | Dantrolene sodium crystal form and preparation method thereof |
-
2008
- 2008-02-25 CN CNA2008101008698A patent/CN101254176A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302461A (en) * | 2011-09-02 | 2012-01-04 | 海南锦瑞制药股份有限公司 | Dantrolene sodium freeze-dried powder injection for injection and preparation method thereof |
| CN106413709A (en) * | 2013-12-05 | 2017-02-15 | 阿勒根公司 | Treatment of spasticity with intrathecal dantrolene |
| CN111825662A (en) * | 2019-04-18 | 2020-10-27 | 丽珠医药集团股份有限公司 | Dantrolene sodium crystal form and preparation method thereof |
| CN111419795A (en) * | 2020-05-09 | 2020-07-17 | 上药东英（江苏）药业有限公司 | Danqulin sodium suspension for injection and preparation method thereof |
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Application publication date: 20080903 |