CN1287776C - Process for preparing houttuyninum sodium injection - Google Patents
Process for preparing houttuyninum sodium injection Download PDFInfo
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- CN1287776C CN1287776C CN 01138903 CN01138903A CN1287776C CN 1287776 C CN1287776 C CN 1287776C CN 01138903 CN01138903 CN 01138903 CN 01138903 A CN01138903 A CN 01138903A CN 1287776 C CN1287776 C CN 1287776C
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- sodium
- injection
- hydroxypropyl
- houttuyfonate
- sodium houttuyfonate
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Abstract
The present invention relates to a preparation method of a sodium houttuyfonate injection. In the method, the dissolvability of the sodium houttuyfonate injection in water is greatly improved. Firstly, hydroxypropyl beta-cyclodextrin is placed in water for injection, and after the hydroxypropyl beta-cyclodextrin is stirred and dissolved, sodium houttuyfonate is added, stirred or ground at the room temperature to obtain a solution of the sodium houttuyfonate; secondly, a hydroxypropyl beta-cyclodextrin inclusion compound of the sodium houttuyfonate is obtained after the vacuum drying or the spray drying or the freeze drying of the obtained solution. The sodium houttuyfonate injection without tween-80 is prepared for the first time so that the injection is safe and stable, and the large dose administration of the sodium houttuyfonate injection becomes possible.
Description
Technical field:
The present invention relates to medical technical field, exactly it is a kind of preparation method of houttuyninum sodium injection.
Background technology:
Sodium Houttuyfonate also is called houttuynine sodium bisulfite, is the sodium sulfite addition product of decanoylacetaldehyde, for China's initiative is used for clinical effective antibiosis anti-inflammatory drug (Zheng Junmin etc.Research Shenyang Pharmacy College journal of Sodium Houttuyfonate polymorphic and bioavailability total 13 phase P51 in 1981), pharmacological evaluation shows, it is 1.25mg/ml to the Mlc of hemophilus influenza, drug-resistant staphylococcus aureus 0.08mg/ml, Bacillus typhi 1.25mg/ml, tubercule bacillus 16ug/ml is to Candida albicans, Cryptococcus histolyticus, red mentagrophytes, dermatomycosis diffusa bacterium ... Deng Mlc be 2ug/ml; Also can the leukocyte increasing phagocytic activity and increase properdin concentration, resist pathogen invasion and attack (" Shanghai medicine application manual P210 ") thereby improve the body non-specific immunity.Recently on the mice of setting up, rat splenectomy model, Sodium Houttuyfonate has regulating action to splenectomy animal cell immunity function, its effect mainly is to cut the function of back lymph node and regulate (the Chinese Pharmacological circular 2001,17 (1): 51～53) that the T cell subsets is realized by strengthening spleen.For caused by cyclophosphamide immunologic hypofunction model mice, can obviously increase the index and spleen index of caused by cyclophosphamide immunologic hypofunction model mice; Strengthen mononuclear-macrophage phagocytic function, delayed hypersensitivity intensity and the inductive splenic T lymphopoiesis of ConA ability; Can also obviously strengthen generation and spleen plaque forming cells haematolysis ability (Shenyang Pharmaceutical University's journal 2000,17 (2): 133～135) of cyclophosphamide model mice serum hemolysin.Oleum Tiglii is caused mice ear, carrageenin to be caused rat paw edema, acetic acid and causes the mouse peritoneal capillary permeability and increase remarkable inhibitory action is all arranged, while can also be suppressed the mouse writhing reaction due to the acetic acid, prolong hot plate reaction incubation period, antagonism formaldehyde causes pain effect (Shenyang Pharmaceutical University's journal 1998,15 (4): 272～275).On Carrageenan causes that granulation tissue hyperplasia all has remarkable inhibitory action due to normal rat and adrenalectomy rat paw edema, rat leukocyte migration and the Oleum Tiglii; Obviously reduce (the Chinese Pharmacological circular 1998,14 (5): 442～444) of PGE content in the inflammation exudate.Clinical infantile pneumonia, senile chronic bronchitis, the adnexitis etc. of being used for, effective percentage reaches more than 84%～90%.There is the author to go up sense (Central Plains doctor's periodical 1991,18 (3): 40 recently with houttuynine sodium bisulfite treatment children's; Jiangxi Chinese medicine 1996,27 (5): 27～28), cure rate is respectively 63.6%, 73.2% as a result, and total effective rate is respectively 95.4%, 87.8%, is better than conventional penicillin treatment.Dosage form from treatment, the effect of injection type is better, but Sodium Houttuyfonate is white or off-white color needle-like or flake-like crystal, is slightly soluble in water, in order to make injection, the essential tween 80 that adds in prescription, its concentration is up to 1.5%, and so high concentration not only easily produces haemolysis, and certain toxicity is arranged, do not meet the requirement of modern medicines preparation.There is the author to study houttuynine sodium bisulfite Benexate Hydrochloride (I) (Chinese Pharmaceutical Journal 1999,34 (3): 167～169), though the dissolubility of I increases to some extent, beta-schardinger dextrin-can not intravenous injection, made dosage form only can supply oral or external, and can not vein or administered intramuscular.
Summary of the invention:
The preparation method that the purpose of this invention is to provide a kind of houttuyninum sodium injection, it has solved the water solublity problem of houttuynine sodium bisulfite, can be made into injection type, and curative effect is provided.It is realized by following scheme: hydroxypropyl is placed water for injection, after the stirring and dissolving, add Sodium Houttuyfonate again, stirring at room or grinding, get the houttuynine sodium bisulfite sodium solution, again with gained solution after vacuum drying or spray drying or lyophilization, Sodium Houttuyfonate hydroxypropyl clathrate, wherein the weight ratio of Sodium Houttuyfonate and hydroxypropyl is 1: 1～1: 100.The optimum range of above-mentioned weight ratio is 1: 5～1: 30.Above-mentioned clathrate can be as the raw material of making injection, powder pin or transfusion.Said injection comprises " injection ", " freeze-dried powder ", " aseptic powder injection ", " Sodium Houttuyfonate glucose injection or transfusion ".Said " freeze-dried powder " is to add suitable proppant (excipient) in the houttuynine sodium bisulfite sodium solution, as " mannitol ", " lactose ", " dextran " etc., gets by lyophilization.Add suitable proppant (excipient) in the houttuynine sodium bisulfite sodium solution, as " mannitol ", " lactose ", " dextran " etc., the powder that obtains by " lyophilization " or " spray drying " carries out aseptic subpackaged getting.Advantage of the present invention is: hydroxypropyl is the derivant of beta-schardinger dextrin-, and its water solublity is high, under the room temperature, can reach (beta-schardinger dextrin-only about 2%) more than 50%, and nontoxic, nonirritant, be a good used for intravenous injection adjuvant.The present invention utilizes hydroxypropyl that houttuynine sodium bisulfite is carried out enclose, hydrotropy, make injection, not only solved the water solublity problem of houttuynine sodium bisulfite fully, and (concentration of Sodium Houttuyfonate in water is about 0.1mg/ml to have improved unit volume Chinese medicine content, the concentration of existing injection is that every 1ml contains the 2mg Sodium Houttuyfonate, contain the 60mg Sodium Houttuyfonate and this preparation can reach every 1ml) and medicine stability, both can be made into injection, also can be made into aseptic powder injection or freeze-dried powder, also can be made into the Sodium Houttuyfonate glucose injection promptly infuses, make injection safer, more stable, a large amount of medications also become possibility, and have improved curative effect.
The specific embodiment:
Embodiment 1: take by weighing hydroxypropyl 6g, place the 6ml distilled water, stirring and dissolving.Other gets the 0.3g Sodium Houttuyfonate, add in the above-mentioned hydroxypropyl solution, stirring at room or ground 30 minutes, the houttuynine sodium bisulfite sodium solution.(weight ratio of medicine and hydroxypropyl is 1: 20).This solution is concentrated into 5ml, gets the houttuynine sodium bisulfite sodium solution of 60mg/ml.
Embodiment 2: take by weighing hydroxypropyl 10g, place 100ml water for injection, stirring and dissolving.Other gets the 1g Sodium Houttuyfonate, adds in the above-mentioned hydroxypropyl solution, and stirring at room 30 minutes is filtered, gained solution, and through vacuum drying, or spray drying, or after the lyophilization, get white powder, i.e. Sodium Houttuyfonate hydroxypropyl clathrate.The infrared spectrum of this clathrate both had been different from Sodium Houttuyfonate, hydroxypropyl, also was different from Sodium Houttuyfonate and hydroxypropyl mixture.(weight ratio of medicine and hydroxypropyl is 1: 10).During this clathrate is soluble in water, make raw material, can be made into injection, powder pin or transfusion with this.
Embodiment 3: take by weighing hydroxypropyl 3g, place 20ml water for injection, stirring and dissolving.Other gets the 0.1g Sodium Houttuyfonate, adds in the above-mentioned hydroxypropyl solution, and stirring at room 20 minutes gets a clear solution (weight ratio of medicine and hydroxypropyl is 1: 30).
Embodiment 4: take by weighing hydroxypropyl 15g, place 100ml water for injection, stirring and dissolving.Other gets the 1g Sodium Houttuyfonate, add in the above-mentioned hydroxypropyl solution, stirring at room added 5g mannitol after 30 minutes, after the stirring and dissolving, add the injection water to 250ml, mixing is used the 0.22um filtering with microporous membrane, gained solution is sub-packed in the cillin bottle, every 1ml carries out lyophilization, gets houttuynine sodium bisulfite sodium freeze-drying powder (every 4mg).(weight ratio of medicine and hydroxypropyl is 1: 15).
Embodiment 5: take by weighing hydroxypropyl 30g, place 100ml water for injection, stirring and dissolving.Other gets the 1g Sodium Houttuyfonate, add in the above-mentioned hydroxypropyl solution, stirring at room added the 10g lactose after 30 minutes, after the stirring and dissolving, add the injection water to 250ml, mixing is used the 0.22um filtering with microporous membrane, gained solution is sub-packed in the cillin bottle, every 5ml carries out lyophilization, gets houttuynine sodium bisulfite sodium freeze-drying powder (every 20mg).
Embodiment 6: take by weighing hydroxypropyl 50g, place 200ml water for injection, after the stirring and dissolving, after adding 15g low molecular dextran heating for dissolving, add the 0.5g active carbon and stirred 15 minutes, filter carbon removal, add the 3g Sodium Houttuyfonate in the gained solution, after the stirring and dissolving, add the injection water to 300ml, mixing, use the 0.22um filtering with microporous membrane, gained solution is sub-packed in the cillin bottle, every 1ml, carry out lyophilization, get houttuynine sodium bisulfite sodium freeze-drying powder (every 10mg).After this powder pin adds sterilized water for injection dissolving, carry out aseptic, pyrogen, haemolysis etc. check all qualified.
Embodiment 7: take by weighing hydroxypropyl 20g, place 200ml water for injection, stirring and dissolving.Other gets the 0.4g Sodium Houttuyfonate, add in the above-mentioned hydroxypropyl solution, 50 ℃ of stirred in water bath are after 15 minutes, add 4.6g mannitol (or lactose, dextran), after the stirring and dissolving, add the injection water to 300ml, mixing is used the 0.22um filtering with microporous membrane, and gained solution carries out spray drying, get the Sodium Houttuyfonate powder, contain Sodium Houttuyfonate 16mg (weight ratio of medicine and hydroxypropyl is 1: 50) in every gram spray drying powder.After this powder added water, can dissolve immediately became clear solution.
Embodiment 8: take by weighing hydroxypropyl 100g and Sodium Houttuyfonate 4g, with placing 80 ℃ of waters for injection of 800ml, stirring and dissolving, add the injection water to 1000ml, mixing is used the 0.22um filtering with microporous membrane, gained solution is sub-packed in the ampoule, every 1ml sterilized 30 minutes for 110 ℃, got houttuynine sodium bisulfite injection.It is all qualified that this injection carries out is aseptic, pyrogen, haemolysis etc. are checked.(weight ratio of medicine and hydroxypropyl is 1: 25).
Embodiment 9: take by weighing hydroxypropyl 8g and glucose for injection 500g, place 1000ml80 ℃ of water for injection, the dissolving back adds the 2g active carbon, stir after-filtration carbon removal in 20 minutes, add Sodium Houttuyfonate 0.4g in the gained solution, stirring and dissolving adds the injection water to 10000ml, mixing, use the 0.22um filtering with microporous membrane, gained solution is sub-packed in the 250ml infusion bottle, sterilizes 30 minutes for 115 ℃, get Sodium Houttuyfonate glucose injection (i.e. transfusion, every contains Sodium Houttuyfonate 10mg).It is all qualified that this injection carries out is aseptic, pyrogen, haemolysis etc. are checked.(weight ratio of medicine and hydroxypropyl is 1: 20).
Embodiment 10: the sample and the Sodium Houttuyfonate glucose injection (drug content is 10mg) that does not add hydroxypropyl of " embodiment nine " are placed 80 ℃ of calorstats jointly, carry out examine stability, after 10 days as a result, Sodium Houttuyfonate in the former sample is 8.1mg, and the latter only remains 1.6mg, has significantly improved the stability of Sodium Houttuyfonate after the adding " hydroxypropyl ".
Claims (7)
1. houttuyninum sodium injection, it is characterized in that: with the injection that Sodium Houttuyfonate and hydroxypropyl are mixed with, wherein the weight ratio of Sodium Houttuyfonate and hydroxypropyl is 1: 1～1: 100.
2. the preparation method of houttuyninum sodium injection as claimed in claim 1, it is characterized in that: hydroxypropyl is placed water for injection, after the stirring and dissolving, add Sodium Houttuyfonate again, stirring at room or grinding, the houttuynine sodium bisulfite sodium solution, again with gained solution after vacuum drying or spray drying or lyophilization, get Sodium Houttuyfonate hydroxypropyl clathrate, wherein the weight ratio of Sodium Houttuyfonate and hydroxypropyl is 1: 1～1: 100.
3. the preparation method of houttuyninum sodium injection according to claim 2, it is characterized in that: the scope of the weight ratio of Sodium Houttuyfonate and hydroxypropyl is 1: 5～1: 30.
4. the preparation method of houttuyninum sodium injection according to claim 2, it is characterized in that: said injection comprises " injection ", " freeze-dried powder ", " aseptic powder injection ", " Sodium Houttuyfonate glucose injection or transfusion ".
5. the preparation method of houttuyninum sodium injection according to claim 4, it is characterized in that: said " freeze-dried powder " is to add proppant in the houttuynine sodium bisulfite sodium solution, gets by lyophilization.
6. the preparation method of houttuyninum sodium injection according to claim 2, it is characterized in that: add proppant in the houttuynine sodium bisulfite sodium solution, the powder that obtains by " lyophilization " or " spray drying " carries out aseptic subpackaged getting.
7. according to the preparation method of claim 5 or 6 described houttuyninum sodium injections, it is characterized in that: proppant is mannitol, lactose, dextran.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01138903 CN1287776C (en) | 2001-12-25 | 2001-12-25 | Process for preparing houttuyninum sodium injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01138903 CN1287776C (en) | 2001-12-25 | 2001-12-25 | Process for preparing houttuyninum sodium injection |
Publications (2)
| Publication Number | Publication Date |
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| CN1359678A CN1359678A (en) | 2002-07-24 |
| CN1287776C true CN1287776C (en) | 2006-12-06 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 01138903 Expired - Fee Related CN1287776C (en) | 2001-12-25 | 2001-12-25 | Process for preparing houttuyninum sodium injection |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1297261C (en) * | 2004-01-20 | 2007-01-31 | 昆明紫健生物技术有限公司 | Fatty acyl acetaldehyde transfusion preparation and its preparing method |
| CN102335271A (en) * | 2004-04-28 | 2012-02-01 | 湖南正清制药集团股份有限公司 | Preparation method and quality control method of heartleaf houttuynia herb injection |
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2001
- 2001-12-25 CN CN 01138903 patent/CN1287776C/en not_active Expired - Fee Related
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| Publication number | Publication date |
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| CN1359678A (en) | 2002-07-24 |
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