CN102755338A - Compound preparation containing fosaprepitant and palonosetron hydrochloride, and preparation method thereof - Google Patents
Compound preparation containing fosaprepitant and palonosetron hydrochloride, and preparation method thereof Download PDFInfo
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Abstract
The invention provides a sterile lyophilized compound preparation containing fosaprepitant and palonosetron hydrochloride, and a preparation method thereof. According to the invention, effective dosages of fosaprepitant dimeglumine and palonosetron hydrochloride are adopted as effective components, and auxiliary materials such as a solubilizer, a complexing agent, an excipient, and an acidity adjusting agent are contained in the preparation. The preparation is filtered, sterilized, sub-packaged, and lyophilized. When in use, the sterile lyophilized compound preparation provided by the invention is added into a solvent, such that injection solution with an appropriate concentration is prepared and can be used. With one time of medication, clinical demands of two treatment medicines can be satisfied, such that patient compliance is improved. The preparation method of the compound preparation is simple, and the method is suitable for industrialized productions.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of compound preparation that contains smooth two meglumines of blissful husky pyrrole and palonosetron Hcl and preparation method thereof.
Background technology
Chemotherapy is one of main means of treatment malignant tumor; Yet chemotherapeutics causes feel sick, vomit is day by day general and serious; Become a clinical severe problem of having to face: if control undesirable, with the quality of life that influences the patient, reduce the compliance of treatment.Vomiting due to the chemotherapy of tumors, its neurotransmitter that forms vomiting reflex is mainly dopamine, acetylcholine, histamine, 5-hydroxy tryptamine and neurokinin.According to treating the above-mentioned mechanism and the clinical efficacy of feeling sick, vomitting that chemotherapeutics causes; Medicine comprises early stage medicine, like dexamethasone (higher therapeutic index), (4) phenothiazines, (5) butyrophenones, (6) metoclopramide and the cannabinoid of (1) dopamine-receptor antagonist, (2) acetylcholine receptor antagonists, (3) corticosteroids; Extensive use in the recent period, higher therapeutic index medicine comprises (1) 5-hydroxy tryptamine 3 receptor antagonists, (2) P material/neurokinin 1 receptor antagonist.
Smooth two meglumines of the husky pyrrole of injection good fortune are P material/neurokinin 1 (NK-1) selectivity high-affinity receptor blocker of Merck (Merck) company exploitation, mainly play a role through blocking-up brain nausea and vomiting signal.Clinically with other Bendectin associating intravenous injections, prevent and treat the acute and tardy property nausea and vomiting that medium emetic and serious emetic anticarcinogen initially or repeatedly causes during medication in chemotherapy (comprising heavy dose of cisplatin).
Palonosetron Hcl is second filial generation 5-hydroxy tryptamine 3 (5-HT3 antagonist) receptor antagonist of hot (Helsinn) company in Hull exploitation; This medicine approximately is 100 times of similar medicine to the affinity of 5-HT3 receptor; Demonstrate the effect of efficient and long lasting 5-HT3 receptor blocking; Multinomial research confirms that its toleration is good, and high to the acute vomiting control rate due to the chemotherapy, untoward reaction is little than other similar medicines.
In the dosage regimen of feeling sick, vomitting that prevention is associated with highly emetic chemotherapy clinically; Recommended to give nk 1 receptor antagonist (husky smooth two meglumines of pyrrole of injection good fortune or oral aprepitant) in first day; Also must give 5-HT3 receptor antagonist (department's fine jade class medicine); Double injection patient compliance is relatively poor respectively, and the doctor uses also inconvenient.Therefore two kinds of medication preparation are become compound preparation, can improve the compliance of clinical application, and can confirm the dosage ratio of two kinds of medicines, for patient and doctor provide convenience by clinical consumption.Given this plant and consider that the pharmaceutical composition of a kind of 5-HT3 receptor antagonist and nk 1 receptor antagonist has been described by Pfizer in patent CN95120539.0, but wherein do not comprise palonosetron Hcl, these two kinds of medicines of smooth two meglumines of the husky pyrrole of good fortune.Do not see at present report as yet about husky smooth two meglumines of pyrrole of good fortune and palonosetron Hcl compound preparation research and development situation.
Summary of the invention
Deficiency to prior art; Of the present invention provide a kind of stable in properties, evident in efficacy, toxic and side effects is few, technology is simple, be fit to the compound preparation that contains smooth two meglumines of blissful husky pyrrole and palonosetron Hcl of suitability for industrialized production, makes the product can be better in clinical practice.
The present invention also provides the method for preparing of this compound preparation, and this method adopts conventional process equipment, is suitable for large-scale production.
The term explanation: the false add plug, lyophilizing term in the pharmaceutics refers to add half the plug, stays the space of lyophilizing gas distillation bottle outlet.
Technical scheme of the present invention is following:
A kind of aseptic freeze-dried compound preparation, wherein, active component also contains solubilizing agent, chelating agent, excipient, acidity regulator, pH value 5.0-8.0 before the lyophilizing for husky smooth two meglumines of pyrrole of the good fortune of treatment effective dose and palonosetron Hcl.
According to aseptic freeze-dried compound preparation of the present invention, it is characterized in that the preceding pH value 6.0-6.5 of lyophilizing.
Described solubilizing agent is selected from polyoxyethylene sorbitan monoleate, polysorbate 20, Polyethylene Glycol, polyoxyethylene castor oil, polyethylene than one of pyrrolidone, poloxamer or combination;
Described chelating agent is selected from one of disodium edetate, triethanolamine, diethylenetriamine pentacarboxylic acid salt, nitrilotriacetic acid sodium or combination;
Described excipient is selected from one of glucose, lactose, mannitol, dextran, sorbitol, arginine, glycine, gelatin hydrolysate or combination;
Described acidity regulator is selected from one of sodium hydroxide, hydrochloric acid, sodium bicarbonate, citric acid, sodium citrate, glacial acetic acid, benzoic acid, boric acid, lactic acid or combination; Described bronsted lowry acids and bases bronsted lowry all uses with the solution form.Preferred especially sodium hydroxide of described acidity regulator and hydrochloric acid, below brief note is sodium hydroxide/hydrochloric acid.
According to the present invention, preferred, a kind of aseptic freeze-dried compound preparation, the consumption of each component before lyophilizing, by per 1000 bottles, every bottle of packing volume is 2-10mL:
Smooth two meglumines of the husky pyrrole of good fortune 150～280g,
Palonosetron Hcl 0.1～0.5g,
Solubilizing agent 40～90g,
Chelating agent 10～25g,
Excipient 200～450g,
Acidity regulator with pH value of solution to being adjusted to 5.0～8.0,
Water for injection 2000-10000mL.
According to the present invention, preferred, a kind of aseptic freeze-dried compound preparation, the consumption of each component before lyophilizing, by per 1000 bottles, every bottle of packing volume is 3-5mL:
Smooth two meglumines of the husky pyrrole of good fortune 180～250g,
Palonosetron Hcl 0.2～0.3g,
Solubilizing agent 55～85g,
Chelating agent 14～19g,
Excipient 280～380g,
Acidity regulator with pH value of solution to being adjusted to 6.0～7.0,
Water for injection 3000～5000mL.
According to the present invention, preferred, a kind of aseptic freeze-dried compound preparation, the consumption of each component before lyophilizing, by per 1000 bottles, every bottle of packing volume is 3-5mL:
Smooth two meglumines of the husky pyrrole of good fortune 188～245.3g,
Palonosetron Hcl 0.25g,
Polyoxyethylene sorbitan monoleate 57.5～75g,
Disodium edetate 14.4～18.8g,
Lactis Anhydrous 287.5～375g,
Sodium hydroxide/hydrochloric acid with pH value of solution to the consumption that is adjusted to 6.0～6.5,
Water for injection 3000～5000mL.
The method for preparing of aseptic freeze-dried compound preparation of the present invention comprises the steps:
By proportioning; Smooth two meglumines of the husky pyrrole of good fortune, palonosetron Hcl, solubilizing agent, chelating agent, excipient stirring and dissolving in an amount of sterile water for injection, are added sterile water for injection to total amount again, and total amount is the 2000-10000mL/1000 bottle; Use acidity regulator to regulate pH value and be 5.0-8.0; Packing after the aseptic filtration, every bottle of packing volume is 2-10mL, lyophilizing.
According to the method for preparing of aseptic freeze-dried compound preparation of the present invention, preferred, with smooth two meglumines of the husky pyrrole of good fortune, palonosetron Hcl, solubilizing agent, chelating agent, excipient stirring and dissolving in an amount of sterile water for injection; Add sterile water for injection again to total amount; Using acidity regulator to regulate pH value and be 6.0-7.0, is 0.22 micron aseptic microporous filter membrane with medicinal liquid through the aperture again, 1000 bottles of packing; Put into freeze dryer behind the false add plug, whole process strict control antibacterial and endotoxin.
According to the method for preparing of aseptic freeze-dried compound preparation of the present invention, further preferred, using acidity regulator to regulate pH value is 6.5.
Method for preparing according to aseptic freeze-dried compound preparation of the present invention; Further preferred; Described lyophilizing is: 1, pre-freeze: under aseptic condition; The medicinal liquid that will pass through degerming is in normal pressure ,-30～-80 ℃ of pre-freezes 30～240 minutes, and 2, sublimation drying: vacuum lyophilization is 6～24 hours under vacuum 5～50 Pascals, temperature-10～-30 ℃ condition, and 3, parsing-desiccation: vacuum drying is 2～18 hours under vacuum 1～5 Pascal, 5～40 ℃ of conditions of temperature.
The present invention adopts three sections step of freeze drying, and 1, pre-freeze stage of product: before sublimation drying, freeze reality to all products; 2, sublimation drying: guarantee product freeze real after gradually elevated temperature make water sublimed; 3, parsing-desiccation: after continuing to be warming up to product temperature and flaggy temperature basically identical, heat preservation and dryness a period of time, dry run finishes.
According to the method for preparing of aseptic freeze-dried compound preparation of the present invention, further preferred,, vacuum drying compresses bottle stopper after finishing, outlet after the release vacuum, gland, inspection, packing are placed 2～8 ℃ of refrigerators and are preserved.
Husky smooth two meglumines of pyrrole of good fortune of the present invention and the aseptic freeze-dried compound preparation of palonosetron Hcl; The injection that is made into suitable concn behind the adding solvent during use uses; Single administration can satisfy the clinical demand of two kinds of medicines in the chemotherapeutic treatment scheme; Improved patient's compliance, and can confirm the dosage and the proportioning of two kinds of medicines, made things convenient for the doctor to use according to clinical consumption.
The method for preparing technology of husky smooth two meglumines of pyrrole of good fortune of the present invention and the aseptic freeze-dried compound preparation of palonosetron Hcl is simple, and safety is controlled, is fit to very much large-scale industrial production.
The specific embodiment
Below in conjunction with embodiment the present invention is explained further details, but be not limited thereto.
The relation of amounting to of the amount that husky smooth two meglumines of pyrrole of the good fortune among the embodiment and the husky pyrrole of good fortune are smooth is: smooth two meglumines of the husky pyrrole of good fortune/smooth quality of the husky pyrrole of good fortune is 188/115.Acidity regulator among the embodiment all adds with the solution form, and for example: sodium hydroxide/hydrochloric acid is meant 2mol/L sodium hydroxide solution and 0.1mol/L hydrochloric acid.
1000 bottles of embodiment 1. preparations, every bottle contains that the husky pyrrole of 115mg good fortune is smooth, the aseptic freeze-dried compound preparation of 0.25mg palonosetron Hcl.
Prescription: the smooth two meglumine 188g of the husky pyrrole of good fortune, palonosetron Hcl 0.25g, polyoxyethylene sorbitan monoleate 57.5g, disodium edetate 14.4g, Lactis Anhydrous 287.5g, sodium hydroxide/hydrochloric acid adds the injection water to cumulative volume 4000mL.
Technology: 1) medicinal liquid configuration: by said prescription weighing; With the husky smooth two meglumine 188g of pyrrole of good fortune and palonosetron Hcl 0.25g, polyoxyethylene sorbitan monoleate 57.5g, disodium edetate 14.4g, Lactis Anhydrous 287.5g stirring and dissolving in an amount of sterile water for injection; Add sterile water for injection again to 4000mL; Using sodium hydroxide/hydrochloric acid to regulate pH value is 6.0, is 0.22 micron aseptic microporous filter membrane with medicinal liquid through the aperture again, 1000 bottles of packing; Put into freeze dryer behind the false add plug halogenated butyl rubber plug, whole process strict control antibacterial and endotoxin; 2) lyophilization: the medicinal liquid that aseptic condition will pass through down degerming was in normal pressure ,-40 ℃ of pre-freezes 120 minutes; Being that 10 Pascals, temperature are-30 ℃ of following vacuum lyophilizations 8 hours in vacuum again, is that 2 Pascals, temperature are 20 ℃ of following vacuum dryings 8 hours in vacuum then.3) compress bottle stopper after drying finishes, slowly discharge outlet after the vacuum, gland, inspection, packing are placed 2～8 ℃ of refrigerators and are preserved.
Use: add injection normal saline or glucose injection (solvent for injection) dissolving, be diluted to the smooth 1mg/mL posterior vein injection of the husky pyrrole of good fortune.
1000 bottles of embodiment 2. preparations, every bottle contains that the husky pyrrole of 120mg good fortune is smooth, the aseptic freeze-dried compound preparation of 0.24mg palonosetron Hcl.
Prescription: the smooth two meglumine 196.2g of the husky pyrrole of good fortune, palonosetron Hcl 0.24g, Tween-80 65g, disodium edetate 16.5g, glucose 325g, sodium hydroxide/hydrochloric acid adds the injection water to cumulative volume 5000mL.
Technology: 1) medicinal liquid configuration: by said prescription weighing, with the smooth two meglumine 196.2g of the husky pyrrole of good fortune, palonosetron Hcl 0.24g; Tween-80 65g, disodium edetate 16.5g, glucose 325g stirring and dissolving is in an amount of sterile water for injection; Add sterile water for injection to 5000mL; Using sodium hydroxide/hydrochloric acid to regulate pH value is 6.5, is 0.22 micron aseptic microporous filter membrane with medicinal liquid through the aperture again, 1000 bottles of packing; Put into freeze dryer behind the false add plug halogenated butyl rubber plug, whole process strict control antibacterial and endotoxin; 2) lyophilization: the medicinal liquid that aseptic condition will pass through down degerming was in normal pressure ,-50 ℃ of pre-freezes 180 minutes; Being that 8 Pascals, temperature are-25 ℃ of following vacuum lyophilizations 10 hours in vacuum again, is that 1 Pascal, temperature are 30 ℃ of following vacuum dryings 6 hours in vacuum again.3) compress bottle stopper after drying finishes, slowly discharge outlet after the vacuum, gland, inspection, packing are placed 2～8 ℃ of refrigerators and are preserved.
Use: add solvent for injection (like injection normal saline or glucose injection) dissolving, be diluted to the smooth concentration of the husky pyrrole of good fortune and be the injection of 1mg/mL posterior vein.
1000 bottles of embodiment 3. preparations, every bottle contains that the husky pyrrole of 130mg good fortune is smooth, the aseptic freeze-dried compound preparation of 0.22mg palonosetron Hcl.
Prescription: the smooth two meglumine 212.6g of the husky pyrrole of good fortune, palonosetron Hcl 0.22g, Tween-80 70g, disodium edetate 17.2g, mannitol 332g, sodium hydroxide/hydrochloric acid adds the injection water to cumulative volume 5000mL.
Technology: 1) medicinal liquid configuration: by said prescription weighing, with the smooth two meglumine 212.6g of the husky pyrrole of good fortune, palonosetron Hcl 0.22g; Tween-80 70g, disodium edetate 17.2g, mannitol 332g stirring and dissolving is in an amount of sterile water for injection; Add sterile water for injection to 5000mL; Using sodium hydroxide/hydrochloric acid to regulate pH value is 7.0, is 0.22 micron aseptic microporous filter membrane with medicinal liquid through the aperture again, 1000 bottles of packing; Put into freeze dryer behind the false add plug halogenated butyl rubber plug, whole process strict control antibacterial and endotoxin; 2) lyophilization: the medicinal liquid that aseptic condition will pass through down degerming was in normal pressure ,-45 ℃ of pre-freezes 160 minutes; In vacuum is that 12 Pascals, temperature are-20 ℃ of following vacuum lyophilizations 12 hours, is that 3 Pascals, temperature are 35 ℃ of following vacuum dryings 5 hours in vacuum again.3) compress bottle stopper after drying finishes, slowly discharge outlet after the vacuum, gland, inspection, packing are placed 2～8 ℃ of refrigerators and are preserved.
Use: add solvent for injection (like injection normal saline or glucose injection) dissolving, be diluted to the smooth concentration of the husky pyrrole of good fortune and be the injection of 1mg/mL posterior vein.
1000 bottles of embodiment 4. preparations, every bottle contains that the husky pyrrole of 150mg good fortune is smooth, the aseptic freeze-dried compound preparation of palonosetron Hcl 0.20g.
Prescription: the smooth two meglumine 245.3g of the husky pyrrole of good fortune, palonosetron Hcl 0.20g, Tween-80 75g, disodium edetate 18.8g, dextrose-40 375g, sodium hydroxide/hydrochloric acid adds the injection water to cumulative volume 4000mL.
Technology: 1) medicinal liquid configuration: by said prescription weighing; With the smooth two meglumine 245.3g of the husky pyrrole of good fortune, palonosetron Hcl 0.20g, Tween-80 75g, disodium edetate 18.8g, dextran-40 375g stirring and dissolving in an amount of sterile water for injection; Add sterile water for injection to 4000mL; Using sodium hydroxide/hydrochloric acid to regulate pH value is 8.0, is 0.22 micron aseptic microporous filter membrane with medicinal liquid through the aperture again, 1000 bottles of packing; Put into freeze dryer behind the false add plug halogenated butyl rubber plug, whole process strict control antibacterial and endotoxin; 2) lyophilization: the medicinal liquid that aseptic condition will pass through down degerming was in normal pressure ,-48 ℃ of pre-freezes 200 minutes; Being that 7 Pascals, temperature are-28 ℃ of following vacuum lyophilizations 11 hours in vacuum again, is that 4 Pascals, temperature are 28 ℃ of following vacuum dryings 7 hours in vacuum then.3) compress bottle stopper after drying finishes, slowly discharge outlet after the vacuum, gland, inspection, packing are placed 2～8 ℃ of refrigerators and are preserved.
Lyophilized formulations among 5. couples of embodiment 1 of embodiment carries out the stability test under the hot conditions
With the sample of preparation among the embodiment 1 40 ℃ of condition held 10 days; Respectively to handling the 0th day, the 5th day and the emphasis quality index of the 10th day sample detects; The result shows that quality is basicly stable under 40 ℃ of hot conditionss of these article; Character, moisture and related substance do not have significant change, and the result sees table 1.
Table 1 hot test result
Lyophilized formulations among 6. couples of embodiment 2 of embodiment carries out the stability test under the illumination condition
With the sample of preparation among the embodiment 2 in illumination 4500Lx ± 500Lx condition held 10 days; Respectively to handling the 0th day, the 5th day and the emphasis quality index of the 10th day sample detects; The result shows that these article quality under illumination condition is basicly stable; Character, moisture and related substance do not have significant change, and the result sees table 2.
Table 2 exposure experiments to light result
| Time | Outward appearance | PH value | Clarity | Moisture (%) | Related substance (%) |
| 0 day | The white loose block | 6.48 | Less than No. 1 titer | 0.57 | 1.05 |
| 5 days | The white loose block | 6.52 | Less than No. 1 titer | 0.83 | 1.21 |
| 10 days | The white loose block | 6.60 | Less than No. 1 titer | 1.19 | 1.37 |
Lyophilized formulations among 7. couples of embodiment 3 of embodiment and the prescription that does not add solubilizing agent, chelating agent carry out the stability contrast under the accelerated test condition.
The prescription that does not add solubilizing agent, chelating agent is: the smooth two meglumine 212.6g of the husky pyrrole of good fortune, and palonosetron Hcl 0.22g, mannitol 332g, sodium hydroxide/hydrochloric acid adds the injection water to cumulative volume 5000mL.Technology is with embodiment 3.
Accelerated test is carried out test in 6 months under 25 ℃ ± 2 ℃, RH60% ± 5% condition.Detect the investigation index in the 0th, 1,2,3,6 sampling at the end of month of duration of test.The result shows that these article quality under the accelerated test condition is basicly stable, and character, moisture and related substance do not have significant change, and it is unstable not contain solubilizing agent and chelating agent prescription, and character, moisture and related substance significantly increase, and the result sees table 3.
Table 3 accelerated test comparing result
Sterile freeze-drying preparation among 8. couples of embodiment 3 of embodiment adopts acidity regulator to be adjusted to different pH value before lyophilizing to carry out the stability contrast under the hot test condition.
Prepare 1000 bottles; Prescription: the smooth two meglumine 245.3g of the husky pyrrole of good fortune, palonosetron Hcl 0.20g, Tween-80 75g; Disodium edetate 18.8g; Dextran-40 375g, it is 5.5,6.0,6.5,7.0,7.5,8.0 that hydro-oxidation sodium/hydrochloric acid is regulated pH value respectively, adds the injection water to cumulative volume 4000mL.
With above-mentioned sample 40 ℃ of condition held 10 days; Respectively to handling the 0th day, the 5th day and the emphasis quality index of the 10th day sample detects; The result shows when these article pH value is 6.0-6.5 that quality is the most stable under 40 ℃ of hot conditionss; Character, moisture and related substance change minimum, so pH value is that 6.0-6.5 is optimum pH.The result sees table 4.
The different pH value hot test of table 4 result
Annotate: the preparation pH value is that product is added the measured value after the injection water redissolves.By this area conventional sense method.
Claims (10)
1. an aseptic freeze-dried compound preparation is characterized in that active component is husky smooth two meglumines of pyrrole of good fortune and the palonosetron Hcl of treatment effective dose, also contains solubilizing agent, chelating agent, excipient, acidity regulator, pH value 5.0-8.0 before the lyophilizing.
2. aseptic freeze-dried compound preparation as claimed in claim 1 is characterized in that the pH value 6.0-6.5 that lyophilizing is preceding.
3. aseptic freeze-dried compound preparation as claimed in claim 1 is characterized in that the consumption of each component before lyophilizing, and by per 1000 bottles, every bottle of packing volume is 2-10mL:
Smooth two meglumines of the husky pyrrole of good fortune 150～280g,
Palonosetron Hcl 0.1～0.5g,
Solubilizing agent 40～90g,
Chelating agent 10～25g,
Excipient 200～450g,
Acidity regulator with pH value of solution to the consumption that is adjusted to 5.0～8.0,
Add the injection water to cumulative volume 2000-10000mL.
4. aseptic freeze-dried compound preparation as claimed in claim 3 is characterized in that the consumption of each component before lyophilizing, and by per 1000 bottles, every bottle of packing volume is 3-5mL:
Smooth two meglumines of the husky pyrrole of good fortune 180～250g,
Palonosetron Hcl 0.2～0.3g,
Solubilizing agent 55～85g,
Chelating agent 14～19g,
Excipient 280～380g,
Acidity regulator with pH value of solution to the consumption that is adjusted to 6.0～7.0,
Add the injection water to cumulative volume 3000-5000mL.
5. like each described aseptic freeze-dried compound preparation of claim 1-4, it is characterized in that described solubilizing agent is selected from polyoxyethylene sorbitan monoleate, polysorbate 20, Polyethylene Glycol, polyoxyethylene castor oil, polyethylene than one of pyrrolidone, poloxamer or combination;
Described chelating agent is selected from one of disodium edetate, triethanolamine, diethylenetriamine pentacarboxylic acid salt, nitrilotriacetic acid sodium or combination;
Described excipient is selected from one of glucose, lactose, mannitol, dextran, sorbitol, arginine, glycine, gelatin hydrolysate or combination;
Described acidity regulator is selected from one of sodium hydroxide, hydrochloric acid, sodium bicarbonate, citric acid, sodium citrate, glacial acetic acid, benzoic acid, boric acid, lactic acid or combination.
6. like each described aseptic freeze-dried compound preparation of claim 1-5, it is characterized in that per 1000 bottles of lyophilized formulations, every bottle of packing volume is 3-5mL before lyophilizing, the consumption of each component:
Smooth two meglumines of the husky pyrrole of good fortune 188～245.3g,
Palonosetron Hcl 0.25g,
Polyoxyethylene sorbitan monoleate 57.5～75g,
Disodium edetate 14.4～18.8g,
Lactis Anhydrous 287.5～375g,
Sodium hydroxide/hydrochloric acid with pH value of solution to the consumption that is adjusted to 6.0～6.5,
Add the injection water to cumulative volume 3000～5000mL.
7. the method for preparing of each described aseptic freeze-dried compound preparation of claim 1-3, by proportioning, with smooth two meglumines of the husky pyrrole of good fortune, palonosetron Hcl, solubilizing agent, chelating agent, excipient stirring and dissolving in an amount of sterile water for injection; Add sterile water for injection again to total amount; Total amount is the 2000-10000mL/1000 bottle, uses acidity regulator to regulate pH value and is 5.0-8.0, packing after the aseptic filtration; Every bottle of packing volume is 2-10mL, lyophilizing.
8. the method for preparing of aseptic freeze-dried compound preparation according to claim 7; It is characterized in that using acidity regulator to regulate pH value and be 6.0-7.0; Be 0.22 micron aseptic microporous filter membrane again with medicinal liquid through the aperture; 1000 bottles of packing are put into freeze dryer behind the false add plug, whole process strict control antibacterial and endotoxin.
9. according to the method for preparing of claim 7 or 8 described aseptic freeze-dried compound preparations, it is characterized in that using acidity regulator to regulate pH value is 6.5.
10. according to the method for preparing of claim 7 or 8 described aseptic freeze-dried compound preparations; It is characterized in that described lyophilizing is: under aseptic condition; The medicinal liquid that will pass through degerming was in normal pressure ,-30～-80 ℃ of pre-freezes 30～240 minutes; Vacuum lyophilization 6～24 hours under vacuum 5～50 Pascals, temperature-10～-30 ℃ condition again, vacuum drying 2～18 hours under vacuum 1～5 Pascal, 5～40 ℃ of conditions of temperature at last.
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| WO2023174330A1 (en) * | 2022-03-17 | 2023-09-21 | 珠海贝海生物技术有限公司 | Lyophilized preparation, and preparation method therefor and use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104971049A (en) * | 2014-04-08 | 2015-10-14 | 石药集团中奇制药技术（石家庄）有限公司 | Freeze-dried preparation containing fosaprepitant and preparation method of freeze-dried preparation |
| CN104971049B (en) * | 2014-04-08 | 2019-05-21 | 石药集团中奇制药技术（石家庄）有限公司 | A kind of lyophilized preparation and preparation method thereof containing Fosaprepitant |
| WO2016175586A3 (en) * | 2015-04-29 | 2016-12-22 | 주식회사 삼양바이오팜 | Pharmaceutical package |
| WO2019226784A1 (en) * | 2018-05-22 | 2019-11-28 | Navinta Iii Inc | Injectable combination products of fosaprepitant and 5-ht3 blocker |
| WO2023174330A1 (en) * | 2022-03-17 | 2023-09-21 | 珠海贝海生物技术有限公司 | Lyophilized preparation, and preparation method therefor and use thereof |
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