CN1209104C - Neohouttuynin sodium freeze-dried powder-injection, and its prepn. method - Google Patents
Neohouttuynin sodium freeze-dried powder-injection, and its prepn. method Download PDFInfo
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- CN1209104C CN1209104C CN 03112411 CN03112411A CN1209104C CN 1209104 C CN1209104 C CN 1209104C CN 03112411 CN03112411 CN 03112411 CN 03112411 A CN03112411 A CN 03112411A CN 1209104 C CN1209104 C CN 1209104C
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- injection
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- dried powder
- houttuyninum
- cyclodextrin
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Abstract
The present invention relates to a freeze-dried powder injection solution of sodium neohouttuyfonate and a preparation method thereof, which belongs to the technical field of medicines. The freeze-dried powder injection solution of sodium neohouttuyfonate is prepared from 0.01% to 40% of sodium neohouttuyfonate, 0.01% to 95% of one or several kinds of cyclodextrin or cyclodextrin derivates and 0 to 97% of excipient vehicle. The preparation method comprises the following steps: the sodium neohouttuyfonate and the cyclodextrin or the cyclodextrin derivates are dissolved in water for injection; the excipient vehicle is added for dissolution; a pH value is regulated; the solution is filtered, the filter liquor is subpackaged, frozen and dried through sublimation to obtain a loosening block product or a powder product. The freeze-dried powder injection solution of the present invention has the advantages of good solubility, no penetrating odor, high biological availability and high stability; clinic use can be safer and more convenient; the present invention can be used for intramuscular injection or intravenous drip and used for treating gynecological inflammation, such as pelvic inflammatory diseases, adnexitis, chronic cervicitis, etc.
Description
(1) technical field
The present invention relates to injection neo-houttuyninum sodium freeze-dried powder injection and preparation method thereof, belong to medical technical field.
(2) background technology
Neo-houttuyninum is artificial composite, chemical name lauroyl acetaldehyde sodium sulfite, this product is easily molten in hot water, slightly soluble in water, ethanol, almost insoluble in chloroform, benzene, easily molten in sodium hydroxide test solution, but decompose (the 5th P273 of national drug standards chemical drugs provincial standard rising national standard) simultaneously.And neo-houttuyninum has the fishy smell flavor, and little smelly, These characteristics makes its preparation and application be subjected to certain limitation.
The usage and dosage of the national drug standards (the 4th P323 of chemical drugs provincial standard rising national standard) new houttuynine sodium bisulfite injection description has been narrated new houttuynine sodium bisulfite injection and can be used for intramuscular injection or intravenous drip, in the points for attention of description, indicate: when low temperature, may separate out milky point or crystallization, in hot water, soak molten after, still can use.This has brought inconvenience for the clinical use of this medicine, the shortcoming of this medicine also has been described:, easily separate out simultaneously in instability storage period.
(3) summary of the invention
The present invention is directed to and remedy the deficiencies in the prior art, a kind of injection neo-houttuyninum sodium freeze-dried powder injection and preparation method thereof is provided.
Injection neo-houttuyninum sodium freeze-dried powder injection of the present invention comprises following component, all is weight percentage:
Neo-houttuyninum 0.01%～40%, in cyclodextrin or the cyclodextrin derivative one or more 0.01%～95%, excipient 0～97%.
Above-mentioned described neo-houttuyninum, content is greater than 98%, with high effective liquid chromatography for measuring.
Above-mentioned cyclodextrin or cyclodextrin derivative are: alpha-cyclodextrin, alpha-cyclodextrin derivant, beta-schardinger dextrin-, beta-cyclodextrin derivative, gamma-cyclodextrin or gamma-cyclodextrin derivant.Molecular weight gets final product by this area normal ranges.
Above-mentioned excipient is selected from one or more in mannitol, lactose, glycine, sorbitol, low molecular dextran, glucose, the hydrolysis gel.Molecular weight gets final product by this area normal ranges.
The preparation method of injection neo-houttuyninum sodium freeze-dried powder injection of the present invention comprises that step is as follows:
(1) gets neo-houttuyninum 0.01%～40%, in cyclodextrin or the cyclodextrin derivative one or more 0.01%～95%, close and place container, the water for injection that adds 200～4000 times of weight of neo-houttuyninum stirs into pasty state, add 70 ℃～85 ℃ waters for injection of 200～4000 times of weight of neo-houttuyninum again, be incubated 70 ℃～85 ℃ dissolvings;
(2) add excipient, dissolving, adjust pH to 4.0～7.0;
(3) solution filters, the filtrate packing;
(4) freezing, carry out sublimation drying, get white loose block or powder-product.
Can add adsorbent pin charcoal after above-mentioned steps (2), stirring at room adopts microporous filter membrane, titanium filter stick or sand filtration rod filtering decarbonization.
Filter employing 0.22～0.45 μ m microporous filter membrane fine straining at above-mentioned steps (3) solution, filtrate is carried out packing by every 0.5ml～10ml.
Freezing method in above-mentioned steps (4) is as follows: per minute reduces by 10 ℃～15 ℃, cools to-30 ℃ to-50 ℃ until solution, keeps 2 hours～8 hours, heats to-20 ℃ to-35 ℃ again.
Preparation finishes, and goods are taken out, and seals, and promptly obtaining character is the injection neo-houttuyninum sodium freeze-dried powder injection of white loose block or powder.
Compared with prior art, excellent results of the present invention is as follows:
1. adopted the cyclodextrin or derivatives thereof, because cyclodextrin, cyclodextrin derivative have special ring-type hollow cylinder type structure, so can with the neo-houttuyninum molecule forming bag mixture, thereby improved the dissolubility of medicine, covered the bad smell of medicine, strengthened stability of drug, reduced the zest of medicine, improved bioavailability of medicament the people.
2. the cyclodextrin or derivatives thereof also can for production procurement provides convenience, improve the productivity as excipient when playing clathration, and this is that general solubilizing agent is irreplaceable.
3. selected lyophilized injectable powder, there is not moisture, thereby improved stability of drug, guaranteed the quality of medicine, the phenomenon of low temperature crystallize can not occur, made clinical use safe ready more, clinical adverse and side effect have been reduced, prolonged the storage period of medicine simultaneously, and injection neo-houttuyninum sodium freeze-dried powder injection has and meets the quick-dissolving characteristics of water, for clinical use provides convenience.
Injection neo-houttuyninum sodium freeze-dried powder injection of the present invention all complies with relevant regulations in the check of items such as content, pyrogen, aseptic, pH, and no antigen has no side effect.And there is not bad abnormal smells from the patient.This product can be used for intramuscular injection or intravenous drip, is used for the treatment of gynecological inflammations such as pelvic inflammatory disease, adnexitis, chronic cervicitis.
(4) specific embodiment
Embodiment 1: injection neo-houttuyninum sodium freeze-dried powder injection, and component is as follows, all is weight percentage:
Neo-houttuyninum 2.0%
HP-22.6%
Mannitol 75.4%
Preparation method is as follows:
Get neo-houttuyninum sodium raw materials 12g, HP-135g, add injection water 3L, stir into pasty state, add 70 ℃～85 ℃ water for injection 3L again, temperature is controlled at 70 ℃～85 ℃ during dissolving, with mannitol 450g dissolving, reuse 1moL/L hydrochloric acid solution adjust pH to 5.6, add pin with charcoal after stirring at room, filtering decarbonization, fine straining.Filtrate is carried out packing by every 2ml, adopts quick freezing, and per minute reduces by 10 ℃, cools to-45 ℃ until solution, keeps 4 hours, heats to-20 ℃ again, carries out sublimation drying, and goods are taken out, and seals, and promptly obtaining character is white loose block or powder.
Embodiment 2: injection neo-houttuyninum sodium freeze-dried powder injection, and component is as follows, all is weight percentage:
Neo-houttuyninum 4.3%
Alpha-cyclodextrin 53.2%
Lactose 42.5%.
Preparation method is as follows:
Get neo-houttuyninum sodium raw materials 30g, alpha-cyclodextrin 375g, add injection water 3L, stir into pasty state, add 70 ℃～85 ℃ water for injection 3L again, temperature is controlled at 70 ℃～85 ℃ during dissolving, add lactose 300g dissolving, reuse 1moL/L hydrochloric acid solution adjust pH to 4.8, add pin with charcoal after stirring at room, filtering decarbonization, fine straining.Filtrate is carried out packing by every 2ml, adopts quick freezing, and per minute reduces by 10 ℃, cools to-40 ℃ until solution, keeps 4 hours, heats to-20 ℃ again, carries out sublimation drying, and goods are taken out, and seals, and promptly obtaining character is white loose block or powder.
Embodiment 3: injection neo-houttuyninum sodium freeze-dried powder injection, and component is as follows, all is weight percentage:
Neo-houttuyninum 5.7%
Gamma-cyclodextrin 65.7%
Glucose 28.5%
Preparation method is as follows:
Get neo-houttuyninum sodium raw materials 60g, gamma-cyclodextrin 690g, add injection water 3L, stir into pasty state, add 70 ℃～85 ℃ water for injection 3L again, temperature is controlled at 70 ℃～85 ℃ during dissolving, add glucose 300g dissolving, reuse 1moL/L hydrochloric acid solution adjust pH to 6.2, add pin with charcoal after stirring at room, filtering decarbonization, fine straining.Filtrate is carried out packing by every 2ml, adopts quick freezing, and per minute reduces by 15 ℃, cools to-45 ℃ until solution, keeps 4 hours, heats to-30 ℃ again, carries out sublimation drying, and goods are taken out, and seals, and promptly obtaining character is white loose block or powder.
The foregoing description product effect is summarized as follows shown in the table.
| Sequence number | Specification | The dissolving situation |
| Embodiment 1 | 4mg | Every bottle adds 2ml water for injection, and jog 5 seconds is instant, the solution clarification. |
| Embodiment 2 | 10mg | Every bottle adds 5ml water for injection, and jog 5 seconds is instant, the solution clarification. |
| Embodiment 3 | 20mg | Every bottle adds 5ml water for injection, and jog 5 seconds is instant, the solution clarification. |
Embodiment 4: injection neo-houttuyninum sodium freeze-dried powder injection, and component is as follows, all is weight percentage:
Neo-houttuyninum 7.4%
HP-92.6%.
Preparation method is as follows:
Get neo-houttuyninum sodium raw materials 60g, HP-750g, add injection water 3L, stir into pasty state, add 70 ℃～85 ℃ water for injection 3L again, temperature is controlled at 70 ℃～85 ℃ during dissolving, reuse 1moL/L hydrochloric acid solution adjust pH to 5.4, add pin with charcoal after stirring at room, filtering decarbonization, fine straining.Filtrate is carried out packing by every 2ml, adopts quick freezing, and per minute reduces by 10 ℃, cools to-40 ℃ until solution, keeps 4 hours, heats to-20 ℃ again, carries out sublimation drying, and goods are taken out, and seals, and promptly obtaining character is white loose block or powder.
Claims (6)
1. the preparation method of injection neo-houttuyninum sodium freeze-dried powder injection, step is as follows:
(1) gets neo-houttuyninum 0.01%～40%, cyclodextrin or HP-0.01%～95%, close and place container, the water for injection that adds 200～4000 times of weight of neo-houttuyninum stirs into pasty state, add 70 ℃～85 ℃ waters for injection of 200～4000 times of weight of neo-houttuyninum again, be incubated 70 ℃～85 ℃ dissolvings;
(2) add excipient, dissolving, adjust pH to 4.0～7.0;
(3) solution filters, the filtrate packing;
(4) freezing, carry out sublimation drying, get white loose block or powder-product.
2. the preparation method of injection neo-houttuyninum sodium freeze-dried powder injection as claimed in claim 1 is characterized in that, adds absorption pin charcoal in step (2) back, and stirring at room adopts microporous filter membrane, titanium filter stick or carbon filter stick filtering decarbonization.
3. the preparation method of injection neo-houttuyninum sodium freeze-dried powder injection as claimed in claim 1 is characterized in that, filters at step (3) solution and adopts 0.22 μ m～0.45 μ m microporous filter membrane fine straining, and filtrate is carried out packing by every 0.5ml-10ml.
4. the preparation method of injection neo-houttuyninum sodium freeze-dried powder injection as claimed in claim 1, it is characterized in that, freezing method in step (4) is as follows: per minute reduces by 10 ℃-15 ℃, cool to-30 ℃ to-50 ℃ until solution, kept 2 hours～8 hours, and heated again to-20 ℃ to-35 ℃.
5. the preparation method of injection neo-houttuyninum sodium freeze-dried powder injection as claimed in claim 1 is characterized in that, described cyclodextrin is: alpha-cyclodextrin, beta-schardinger dextrin-or gamma-cyclodextrin.
6. the preparation method of injection neo-houttuyninum sodium freeze-dried powder injection as claimed in claim 1, it is characterized in that described excipient is selected from one or more in mannitol, lactose, glycine, sorbitol, low molecular dextran, glucose, the hydrolysis gel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03112411 CN1209104C (en) | 2003-06-10 | 2003-06-10 | Neohouttuynin sodium freeze-dried powder-injection, and its prepn. method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03112411 CN1209104C (en) | 2003-06-10 | 2003-06-10 | Neohouttuynin sodium freeze-dried powder-injection, and its prepn. method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1459284A CN1459284A (en) | 2003-12-03 |
| CN1209104C true CN1209104C (en) | 2005-07-06 |
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| CN 03112411 Expired - Fee Related CN1209104C (en) | 2003-06-10 | 2003-06-10 | Neohouttuynin sodium freeze-dried powder-injection, and its prepn. method |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1297260C (en) * | 2004-01-20 | 2007-01-31 | 昆明紫健生物技术有限公司 | Fatty acyl acetaldehyde powder projection and its preparing method |
| CN100336523C (en) * | 2005-10-07 | 2007-09-12 | 邹巧根 | Rhubarb lyophilized injection and preparation method thereof |
| CN100336519C (en) * | 2005-10-07 | 2007-09-12 | 邹巧根 | Snakegourd peel lyophilized powder injection and its preparation process |
| CN100417416C (en) * | 2006-03-07 | 2008-09-10 | 中国药科大学 | Medicine composition containing neohouttuynin sodium and solutol HS15 |
| CN102846563B (en) * | 2012-10-10 | 2014-10-08 | 德州德药制药有限公司 | Injection composition of pemetrexed disodium and preparation method of injection composition |
| CN103265459B (en) * | 2013-06-03 | 2015-09-09 | 四川省惠达药业有限公司 | A kind of novel sodium houttuyfonate compound, its preparation method and pharmaceutical composition thereof |
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2003
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