CN101190214B - Paclitaxel injection and preparation method thereof - Google Patents
Paclitaxel injection and preparation method thereof Download PDFInfo
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- CN101190214B CN101190214B CN200710026746XA CN200710026746A CN101190214B CN 101190214 B CN101190214 B CN 101190214B CN 200710026746X A CN200710026746X A CN 200710026746XA CN 200710026746 A CN200710026746 A CN 200710026746A CN 101190214 B CN101190214 B CN 101190214B
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Abstract
The invention relates to a paclitaxel injection and a preparation method of the injection: (1) 200 to 400ml of absolute alcohol and 200 to 400ml of normal saline are taken to be stirred, and 150 to 400ml of polyethylene glycol 400 is added to be evenly mixed; (2) 20 to 40g of tween-80 is added in to the mixture of (1) to be evenly mixed, and then 0.2 to 0.5g of active carbon used for injection isadded to be heated by 35 to 40 DEG C, and raw filtering is carried out and the PH value is controlled to be between 3 to 5; filtering is done and filling and sealing process is carried out; sterilization is carried out for 20 to 35 minutes at the temperature of 100 to 125 DEG C; (3) a transfusion bottle is washed and then is dried for 25 to 35 minutes the temperature of 230 to 260 DEG C, and butyl rubber plug is sterilized; (4) 0.6 to 3g of paclitaxel is taken to be added into the mixture of (2) for dissolving, and then sterilization and filtering are done; and then the solution is filled into the transfusion bottle in the sterilized environment; finally, the bottle is sealed to get the finished product. The invention can prepare safe and reliable paclitaxel injection, by adopting the method of preparing menstruum firstly and paclitaxel solution secondly, the quality of the injection is guaranteed.
Description
Technical field
The present invention relates to field of medicaments, particularly relate to a kind of paclitaxel injection and preparation method thereof.
Background technology
Paclitaxel is a kind of antineoplastic agent that extraction separation obtains from taxaceae Chinese yew genus plants Ramulus et folium taxi cuspidatae.It has unique mechanism of action, by inducing and promoting tubulin polymerization, assembling and stabilize microtubules effect, stop the growth of tumor cell, evident in efficacy to ovarian cancer, breast carcinoma, incidence cancer, lung cancer in non-cellule type and carcinoma of prostate, be broad-spectrum anti-cancer drug.Nineteen ninety-five was in China's approval listing in U.S.'s listing in 1993.Paclitaxel is considered to so far one of human the most effective cancer therapy drug of finding, also is present whole world antitumor drug the most salable.
Paclitaxel dissolves in methanol, ethanol or chloroform, and almost insoluble in water, the dissolubility in water has only 0.006mg/ml, and effectively bioavailability is low in human body.Paclitaxel is dissolved with polyoxyethylene castor oil and dehydrated alcohol with 1: 1 mixed solvent in the paclitaxel injection of present clinical use system, make the medicinal liquid that 5ml contains the 30mg paclitaxel, before the clinical use, need to instil with normal saline or 5% glucose injection dilution posterior vein.Relatively large because of the amount for the treatment of required paclitaxel, need many bottles of paclitaxel injections.In addition, polyoxyethylene castor oil can cause histamine release in the human body, and anaphylaxis takes place, and anaphylaxiss such as medicine such as erythra, rapid breathing, bronchospasm, hypotension will appear in several minutes in part patient after instillation.External report, anaphylactoid incidence rate is 39%, domesticly is reported as 11～12%, and wherein the severe allergic reaction incidence rate is 2%, is mainly I type speed and sends out anaphylaxis, and severe allergic reaction often occurs in the back 2～3min that instils, and can cause death.For the generation of Polyglucan reaction, at present, take before a few hours of instiling, to take hydryllin such as diphenhydramine, dexamethasone more, use very inconvenience.
Summary of the invention
Purpose of the present invention is a solvent with regard to providing a kind of mixed solution that does not contain polyoxyethylene castor oil, safe, stable paclitaxel injection and preparation method thereof.
The present invention can be realized by following mode: 1000ml paclitaxel injection of the present invention is formed by the feedstock production of following consumption proportion: paclitaxel 0.6～3g, dehydrated alcohol 200～400ml, PEG400 150～400ml, tween 80 20～40g, needle-use activated carbon 0.2～0.5g and normal saline 200～400ml.Its preparation method is: (1) adds PEG400 150～400ml after getting dehydrated alcohol 200～400ml, normal saline 200～400ml stirring, mixes thoroughly; (2) in (1), add Tween 80 20～40g, mix thoroughly, add 0.2～0.5g needle-use activated carbon, heat 35～40 ℃ of absorption, the coarse filtration carbon removal, pH value is 3～5, filters, embedding is at 100～125 ℃ of 20～35min that sterilize down; (3) with after the glass infusion bottle cleaning, in 230～260 ℃ of drying 25～35min, the butyl rubber plug sterilization; (4) get paclitaxel 0.6～3g and add dissolving in (2), aseptic filtration under aseptic purification condition, pours into glass infusion bottle, seals, and is mixed with paclitaxel injection.
Described paclitaxel injection adopts the bulk capacity injection dosage form.
Described bulk capacity injection dosage form is that every 50ml paclitaxel injection contains paclitaxel 30mg, 100mg or 150mg.
The present invention has following characteristics:
1. the present invention is a solvent with the mixed solution that does not contain polyoxyethylene castor oil, the paclitaxel injection of preparation safety and stability.
Polyoxyethylene castor oil has good solubilization to paclitaxel, but can cause histamine release in the human body and anaphylaxis takes place, and interacts with igelite transfusion device commonly used, and lixiviate goes out plasticizer phthalic acid dioctyl ester wherein, causes toxicity.Do the solvent of paclitaxel injection without polyoxyethylene castor oil, just can avoid consequent anaphylaxis.The present invention is a solvent with the solvent system that does not contain polyoxyethylene castor oil, dissolving paclitaxel, preparation paclitaxel injection.This solvent system comprises solvent and cosolvent.Solvent has ethanol, PEG400 and normal saline, and cosolvent has Tween 80.The solvent system each component is compatibility according to a certain percentage, both can guarantee to dissolve fully paclitaxel, can guarantee that again the paclitaxel injection preparing out is with normal saline or the dilution of 5% glucose injection after, keep clear and bright certain hour and unlikelyly separate out the paclitaxel crystallization.Safety testing shows that this injection intravenous drip can not cause allergic reaction and the vascular stimulation reaction, does not see coagulation and haemolysis yet, shows this injection clinical vein administration safety.
The present invention carries out stability test, 25 ℃ ± 2 ℃ of test temperatures, establishing criteria: the national drug standards WS of National Drug Administration
1-(X-026)-2001Z, the result shows: the present invention is through accelerated test, and quality is up to specification, and its quality is stable, sees Table 1, table 2.
Table 1 paclitaxel injection stability accelerated test result
Table 2 paclitaxel injection stability long-term test results
2. adopt and join solvent earlier, after join the method for paclitaxel solution, guaranteed the quality of injection.
Paclitaxel is a heat-sensitive materials, can be destroyed under hot conditions, as adopt conventional heating absorption, and the method for high temperature sterilize, paclitaxel will be destroyed.The present invention is solvent, cosolvent mixed dissolution, sterilization, be made into solvent after, dissolve paclitaxel again, degerming is filtered, and so neither influences the content of paclitaxel, does not increase related substance again, aseptic, bacterial endotoxin passed examination can guarantee the quality of injection.
3. adopt the bulk capacity injection dosage form.The existing paclitaxel injection that uses belongs to small-volume injection, and 5ml contains paclitaxel 30mg, during use, gets in paclitaxel injection adding normal saline or 5% glucose injection and dilutes.Press the 150mg Rapid Dose Calculation, get 5 injection, operate cumbersome, the possibility of increase polluting.Paclitaxel injection of the present invention then is a bulk capacity injection, and specification is respectively every 50ml and contains paclitaxel 30mg, 100mg or 150mg paclitaxel injection, and is easy to use, reduces the chance of polluting.During use, with the present invention and normal saline or 5% glucose injection mixed diluting, diluent can keep the clear and bright of certain hour.When the present invention used, speed was dripped in control, can keep 3-5h fully and instil.
The specific embodiment
Below in conjunction with embodiment, the invention will be further described, but it is not represented as unique embodiment of the present invention.
Embodiment one
After getting dehydrated alcohol 400ml, normal saline 300ml stirring, add PEG400 300ml, stir; Then, add Tween 80 40g, stir, add the 0.25g needle-use activated carbon, heat 35 ℃ of absorption, the coarse filtration carbon removal, pH value is 3, with 0.22 μ m filtering with microporous membrane, embedding, at 115 ℃ of 30min that sterilize down, is solvent; After the cleaning of glass infusion bottle usefulness potassium dichromate sulfuric acid solution, in 260 ℃ of dry 25min, butyl rubber plug is sterilized; Get in the paclitaxel 3g adding solvent and dissolve, aseptic filtration under aseptic purification condition, pours into glass infusion bottle and seals, and making specification is that every 50ml contains paclitaxel 150mg paclitaxel injection.
Embodiment two
After getting dehydrated alcohol 400ml, normal saline 300ml stirring, add PEG400 300ml, stir; Then, add Tween 80 30g, stir, add the 0.3g needle-use activated carbon, heat 40 ℃ of absorption, the coarse filtration carbon removal, pH value is 5, with 0.3 μ m filtering with microporous membrane, embedding, at 125 ℃ of 20min that sterilize down, is solvent; After the cleaning of glass infusion bottle usefulness potassium dichromate sulfuric acid solution, in 230 ℃ of dry 35min, butyl rubber plug is sterilized; Get in the paclitaxel 2g adding solvent and dissolve, aseptic filtration under aseptic purification condition, pours into glass infusion bottle and seals, and making specification is that every 50ml contains paclitaxel 100mg paclitaxel injection.
Embodiment three
After getting dehydrated alcohol 300ml, normal saline 400ml stirring, add PEG400 300ml, stir; Then, add Tween 80 20g, stir, add the 0.5g needle-use activated carbon, heat 40 ℃ of absorption, the coarse filtration carbon removal, pH value is 5, with 0.4 μ m filtering with microporous membrane, embedding, at 100 ℃ of 35min that sterilize down, is solvent; After the cleaning of glass infusion bottle usefulness potassium dichromate sulfuric acid solution, in 250 ℃ of dry 30min, butyl rubber plug is sterilized; Get in the paclitaxel 0.6g adding solvent and dissolve, aseptic filtration under aseptic purification condition, pours into glass infusion bottle and seals, and making specification is that every 50ml contains paclitaxel 30mg paclitaxel injection.
Claims (4)
1. paclitaxel injection, it is characterized in that the 1000ml paclitaxel injection is formed by the feedstock production of following consumption proportion: paclitaxel 0.6～3g, dehydrated alcohol 200～400ml, PEG400 150～400ml, tween 80 20～40g, needle-use activated carbon 0.2～0.5g and normal saline 200～400ml.
2. paclitaxel injection according to claim 1 is characterized in that described paclitaxel injection adopts the bulk capacity injection dosage form.
3. paclitaxel injection according to claim 2 is characterized in that described bulk capacity injection dosage form is that every 50ml paclitaxel injection contains paclitaxel 30mg, 100mg or 150mg.
4. preparation method of taxol injection according to claim 1 is characterized in that:
(1) get dehydrated alcohol 200～400ml, normal saline 200～400ml and stir after, add PEG400 150～400ml, mix thoroughly;
(2) in (1), add Tween 80 20～40g, mix thoroughly, add 0.2～0.5g needle-use activated carbon, heat 35～40 ℃ of absorption, the coarse filtration carbon removal, pH value is 3～5, filters, embedding is at 100～125 ℃ of 20～35min that sterilize down;
(3) with after the glass infusion bottle cleaning, in 230～260 ℃ of drying 25～35min, the butyl rubber plug sterilization;
(4) get paclitaxel 0.6～3g and add dissolving in (2), aseptic filtration under aseptic purification condition, pours into glass infusion bottle, seals, and is mixed with paclitaxel injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN200710026746XA CN101190214B (en) | 2007-01-31 | 2007-01-31 | Paclitaxel injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN200710026746XA CN101190214B (en) | 2007-01-31 | 2007-01-31 | Paclitaxel injection and preparation method thereof |
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| CN101190214A CN101190214A (en) | 2008-06-04 |
| CN101190214B true CN101190214B (en) | 2010-09-15 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250047B (en) * | 2011-08-26 | 2013-06-05 | 贺金凤 | Preparation method of taxol compound |
| CN102716095B (en) * | 2012-06-29 | 2013-08-21 | 海南灵康制药有限公司 | Paclitaxel vesicle type phospholipid gel injection |
| CN102772361B (en) * | 2012-08-28 | 2013-08-21 | 吴静 | Medicament composition with docetaxel |
| CN104644548B (en) * | 2013-11-22 | 2018-09-18 | 北京康辰药业股份有限公司 | Lecithin is as taxol and its combination of derivative injection medicine and application |
| CN110075066A (en) * | 2019-06-17 | 2019-08-02 | 安徽恒星制药有限公司 | A kind of tacrolimus injection preparation and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1502332A (en) * | 2002-11-25 | 2004-06-09 | 刘云清 | Process for preparing taxol self-emulsified solid nano granule-injection taxol of anti-cancer medicine |
| CN1723887A (en) * | 2005-07-20 | 2006-01-25 | 重庆福瑞制药有限公司 | Paclitaxel injection, and its prepn. method |
| CN1868459A (en) * | 2006-06-19 | 2006-11-29 | 云南省玉溪望子隆生物制药有限公司 | Docetaxel freeze-dried powder-injection, and its prepn. method |
-
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- 2007-01-31 CN CN200710026746XA patent/CN101190214B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1502332A (en) * | 2002-11-25 | 2004-06-09 | 刘云清 | Process for preparing taxol self-emulsified solid nano granule-injection taxol of anti-cancer medicine |
| CN1723887A (en) * | 2005-07-20 | 2006-01-25 | 重庆福瑞制药有限公司 | Paclitaxel injection, and its prepn. method |
| CN1868459A (en) * | 2006-06-19 | 2006-11-29 | 云南省玉溪望子隆生物制药有限公司 | Docetaxel freeze-dried powder-injection, and its prepn. method |
Non-Patent Citations (2)
| Title |
|---|
| 陆彬.药剂学 1.中国医药科学出版社,2003,207-239. |
| 陆彬.药剂学 1.中国医药科学出版社,2003,207-239. * |
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| CN101190214A (en) | 2008-06-04 |
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Owner name: GUANGDONG KELUN PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: GUANGDONG QINGFA PHARMACEUTICAL INDUSTRY CO., LTD. |
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Address after: 514031, on the west side of Ring Road, Meizhou, Guangdong Patentee after: GUANGDONG KELUN PHARMACEUTICAL CO., LTD. Address before: 514031, on the west side of Ring Road, Meizhou, Guangdong Patentee before: Guangdong Qingfa Pharmaceutical Industry Co., Ltd. |