CN1456162A - Injection of leucovorin calcium and its preparing method - Google Patents
Injection of leucovorin calcium and its preparing method Download PDFInfo
- Publication number
- CN1456162A CN1456162A CN 03121530 CN03121530A CN1456162A CN 1456162 A CN1456162 A CN 1456162A CN 03121530 CN03121530 CN 03121530 CN 03121530 A CN03121530 A CN 03121530A CN 1456162 A CN1456162 A CN 1456162A
- Authority
- CN
- China
- Prior art keywords
- injection
- adjuvant
- principal agent
- calcium levofolinate
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
A calcium levo-pteroyglutamite injection in the form liquid or freeze dried powder for treating anemia and tumor is prepared from calcium levo-pteroyglutamite, mannitol, dextro-glycoside, glucose, sodium chloride, hydrolytic protein, at least one additive, and water for injection. Its advantages are high curative effect and low cost.
Description
Technical field
What the present invention relates to is a kind of with injection medicament and the preparation method of calcium levofolinate as main active, is mainly used in anti-anemia and the detoxifcation antagonist in tumor pharmacother etc.
Background technology
Calcium levofolinate is referred to as (6S)-calcium folinate again, and its medical value is more and more paid attention to by people, in particular for the aspects such as detoxifcation antagonist in treatment anemia and the tumor pharmacother.Therefore be that active component is made the medicine of various medicaments and the pharmaceutical technology of being correlated with is existing much open on relevant medical journal with the calcium levofolinate.But at present because medicaments preparation technology is perfect inadequately, the manufacture method complexity, in addition adjuvant select for use unreasonable, cause this this cost of medicaments preparation higher, the therapeutic effect of prepared medicament is undesirable, and the kind of medicament is comparatively single, is difficult to apply in enormous quantities.
Summary of the invention
The objective of the invention is to utilize producing of existing calcium levofolinate, is active component with it, and the injection medicament and the preparation method of a kind of calcium levofolinate that forms with adjuvant of joining.It is to be the active component principal agent with the calcium levofolinate, being equipped with adjuvant mixes, contain at least a adjuvant in mannitol, dextran, glucose, sodium chloride, the hydrolyzed protein in the described injection medicament, water for injection is solvent, and the weight proportion of principal agent and adjuvant is 1: 0.5-1: 500.
Described injection medicament is meant injection and injectable powder. injectable powder of the present invention is meant that calcium levofolinate adds an amount of water for injection and adjuvant makes after super-dry.Wherein by at least a adjuvant of forming in mannitol, dextran, glucose, sodium chloride, the hydrolyzed protein, and the every bottled amount of the principal agent of injectable powder is at 2--600mg by 20mg for 50-150mg principal agent proportioning.
A kind of preparation method of producing aforesaid injection medicament, it is that principal agent and adjuvant are dissolved with water for injection, adding sodium chloride is an amount of, solution was through medicinal carbon 50-60 ℃, 10 minutes insulation adsorption filtration, through filtering with microporous membrane, make sterile solution again, drying is made injectable powder again.
Described drying is carried out at low temperatures, it be with sterile solution in accordance with regulations weight fraction be loaded in the cillin bottle of dry sterilization, at-30--40 ℃ precooling 2-3 hour ,-36--20 ℃ sublimation drying 15 minutes, 30 ℃ after dry again 20-25 hour, the Zha Gaifengkou packing forms.
Described drying is to be sub-packed in cillin bottle again or to be loaded on cillin bottle earlier by sterilization lyophilizing, pulverizing, and after lyophilization, the Zha Gaifengkou packing forms.
Described drying also can adopt spray drying method, and it is that weight fraction is loaded in the cillin bottle in accordance with regulations with sterile solution low-temperature reduced-pressure spray drying, pulverizing, and the Zha Gaifengkou packing forms.
Injection of the present invention, wherein proportioning has 650-900mg sodium chloride, 30-100ml water for injection solvent in the 50-150mg principal agent, and the amount of principal agent is the preparation of the different loading amount specifications of 0.01-0.5% of liquor weight.
Described injection is 100ml and makes high capacity or 30ml and make low capacity injection liquor, wherein also contains proper amount of sodium hydroxide and sodium pyrosulfite in the liquor.
A kind of liquor preparation method of producing injection medicament, it is that principal agent and adjuvant are dissolved with water for injection, with 50-60 ℃, 10 minutes insulation adsorption filtration of solution process medicinal carbon, again through filtering with microporous membrane, make sterile solution, fill is in cillin bottle, and the Zha Gaifengkou packing forms.
Above-described sterile solution is regulated PH to 7.0-8.0 with sodium hydroxide.
It is simple that the present invention has processing technology, easy to use, reliable, safe and practical, can realize suitability for industrialized production, and work efficiency improves greatly, and the therapeutic effect of medicament is obvious, can reduce production costs, and is suitable for characteristics such as wide popularization and application.
The specific embodiment
The invention relates to and contain the detoxifcation antagonist that is used for tumor pharmacother of calcium levofolinate, anti-anemia injection medicament and preparation technology thereof.
Injectable powder of the present invention comprises: injection freeze-dried products and injectable sterile powder, and its production technology has lyophilization, hypobaric drying method, spray drying method;
The injectable powder medicine that makes with drying under reduced pressure becomes block or Powdered crystallization, and outward appearance is relatively poor; Injectable powder is made in the direct lyophilizing of solution that will contain calcium levofolinate.Preparation becomes the block crystallization of loose shape, and outward appearance is full attractive in appearance, and its finished product is measured its content and related substance with high-efficient liquid phase technique, shows that product quality will stablize with the injectable powder that hypobaric drying method makes.
The preparation of injection freeze-dried products is that the solution that will contain principal agent and adjuvant quantitatively is sub-packed in the cillin bottle under aseptic condition, makes injectable powder through freeze drying process.The preparation of injectable sterile powder is that the sterile solution of content and adjuvant is placed aseptic freeze-dried in the deep bid, pulverizing, by quantitatively being sub-packed in the cillin bottle, rolls lid, seals promptly.Said adjuvant comprises in mannitol, dextran, glucose, sodium chloride, the hydrolyzed protein at least a.The ratio of principal agent and adjuvant is 1: 0.5 to 1: 500, and adjuvant can single use or compound use.The regular size of calcium levofolinate is the 50mg principal agent, the 20mg glucose; The 100mg principal agent, the 20mg glucose; The 150mg principal agent, the 20mg glucose.
The method for preparing injectable powder is: principal agent and adjuvant are dissolved with water for injection, it is an amount of to add sodium chloride, sodium hydroxide solution is regulated pH to 7.0～8.0, with solution through 50～60 ℃ of 0.5% medicinal carbons insulation in 10 minutes adsorption filtrations, again through 0.22 μ m filtering with microporous membrane, make sterile solution, can prepare injectable powder by the following method:
One, the preparation of injection freeze-dried products: with above-mentioned sterile solution in accordance with regulations weight be sub-packed in (dry sterilization) in the cillin bottle respectively,-30～-40 ℃ of pre-freezes 2～3 hours ,-36～-20 ℃ of sublimation dryings 15 hours, 30 ℃ again after dry 20～25 hours, roll the cap seal mouth, packing.
Two, the preparation of injectable sterile powder: 1, freezing packing method: with aseptic freeze-dried in the above-mentioned aseptic parenteral solution placement deep bid, pulverize, weight fraction is loaded in the cillin bottle in accordance with regulations, rolls the cap seal mouth, packing.2, freeze-drying: with above-mentioned sterile solution in accordance with regulations dosage be loaded on (dry sterilization) in the cillin bottle respectively, after the lyophilization, roll the cap seal mouth, the packing.Three, spray drying method: with sterile solution low-temperature reduced-pressure spray drying, pulverize, weight fraction is loaded in the cillin bottle in accordance with regulations, rolls the cap seal mouth, packing.
About the proportioning embodiment (prescription) of injectable powder principal agent and adjuvant has:
1, calcium levofolinate 50mg, Dextran-20 mg, water for injection 10ml; 2, calcium levofolinate 100mg, Dextran-20 mg, water for injection 20ml; 3, calcium levofolinate 150mg, Dextran-20 mg, water for injection 30ml; 4, calcium levofolinate 50mg, mannitol 20mg, water for injection 10ml; 5, calcium levofolinate 100mg, mannitol 20mg, water for injection 20ml; 6, calcium levofolinate 150mg, mannitol 20mg, water for injection 30ml;
Above-mentioned principal agent and adjuvant are white or the loose shape solid of off-white color through the prepared injectable powder of preparation method of the present invention, and outward appearance is full.Prescription 1,4 lyophilized solid in vibration experiment is frangible.
The preparation technology of injection of the present invention is: principal agent and adjuvant are dissolved with water for injection, regulate pH to 7.0～8.0 with sodium hydroxide, with solution through 50～60 ℃ of 0.5% medicinal carbons, 10 minutes the insulation adsorption filtration, again through 0.22 μ m filtering with microporous membrane, make sterile solution, fill is rolled the cap seal mouth in cillin bottle, packing promptly.
The formulation Example of this injection liquor that makes by said method includes the prescription of bulk capacity injection: 1, calcium levofolinate 50mg, and sodium chloride 810mg, sodium hydroxide is an amount of, and sodium pyrosulfite is an amount of, water for injection 100ml; 2, calcium levofolinate 100mg, sodium chloride 749mg, sodium hydroxide is an amount of, and sodium pyrosulfite is an amount of, water for injection 100ml; 3, calcium levofolinate 150mg, sodium chloride 687mg, sodium hydroxide is an amount of, and sodium pyrosulfite is an amount of, water for injection 100ml.
The prescription of injection with small volume agent: 1, calcium levofolinate 50mg, sodium chloride 810mg, sodium hydroxide is an amount of, and sodium pyrosulfite is an amount of, water for injection 30ml; 2, calcium levofolinate 50mg, sodium chloride 810mg, sodium hydroxide is an amount of, and sodium pyrosulfite is an amount of, water for injection 30ml; 3, calcium levofolinate 50mg, sodium chloride 810mg, sodium hydroxide is an amount of, and sodium pyrosulfite is an amount of, water for injection 30ml.
Claims (10)
1, a kind of injection medicament of calcium levofolinate, it is to be the active component principal agent with the calcium levofolinate, being equipped with adjuvant mixes, it is characterized in that containing in the described injection medicament at least a adjuvant in mannitol, dextran, glucose, sodium chloride, the hydrolyzed protein, water for injection is solvent, and the weight proportion of principal agent and adjuvant is 1: 0.5-1: 500.
2, the injection medicament of calcium levofolinate according to claim 1 is meant injection and injectable powder.Injection comprises small-volume injection and bulk capacity injection.Injectable powder comprises injection freeze-dried products and sterile injection powder packaged preparation.
3, injectable powder according to claim 1 is characterized in that being meant that principal agent adding adjuvant adds the dissolving of injection water and makes solution and the injectable powder after super-dry, wherein by at least a adjuvant of forming in the adjuvants such as mannitol, dextran, and the every bottled amount of the principal agent of injectable powder is at 2～600mg by 20mg for 50～150mg principal agent proportioning.
4, the injection of calcium levofolinate according to claim 1, it is characterized in that described injection medicament is a liquor, wherein proportioning has 650～900mg sodium chloride, 10～1000ml water for injection adjuvant in 50～150mg principal agent, and the amount of principal agent is the preparation of 0.01～0.5% different loading amount specifications of liquor weight.
5, the injection of calcium levofolinate according to claim 3, it is characterized in that described water for injection is that solvent is made 30～1000ml high capacity medicament or made the agent of 10～30ml low capacity injection solution, wherein also contains proper amount of sodium hydroxide and sodium pyrosulfite in the solution.
6, a kind of preparation method as claim 1 or 3 described calcium levofolinate injectable powder, it is that principal agent and adjuvant are dissolved with water for injection, it is an amount of to add sodium chloride, solution was through medicinal carbon 50-60 ℃, 10 minutes insulation adsorption filtration, again through filtering with microporous membrane, make sterile solution, drying is made injectable powder again.
7, the preparation method of calcium levofolinate injection medicament according to claim 6, it is characterized in that described drying carries out at low temperatures, it be with sterile solution in accordance with regulations weight fraction be loaded in the cillin bottle of dry sterilization, at-30--40 ℃ precooling 2-3 hour,-36--20 ℃ sublimation drying 15 minutes, 30 ℃ after dry again 20-25 hour, the Zha Gaifengkou packing forms.
8, the preparation method of calcium levofolinate injection medicament according to claim 6 is characterized in that described drying is to be sub-packed in cillin bottle again or to be loaded on cillin bottle earlier by sterilization lyophilizing, pulverizing, and after lyophilization, the Zha Gaifengkou packing forms.
9, the preparation method of calcium levofolinate injection medicament according to claim 6, it is characterized in that described drying also can adopt spray drying method, it is that weight fraction is loaded in the cillin bottle in accordance with regulations with sterile solution low-temperature reduced-pressure spray drying, pulverizing, and the Zha Gaifengkou packing forms.
10, a kind of preparation method as claim 1 or 4 or 5 described l-leucovorin calcium injections, it is that principal agent and adjuvant are dissolved with water for injection, with 50-60 ℃ of insulation adsorption filtration of 10 minutes of solution process medicinal carbon, again through filtering with microporous membrane, make sterile solution, fill is in cillin bottle, and the Zha Gaifengkou packing forms.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03121530 CN1456162A (en) | 2003-04-01 | 2003-04-01 | Injection of leucovorin calcium and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03121530 CN1456162A (en) | 2003-04-01 | 2003-04-01 | Injection of leucovorin calcium and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1456162A true CN1456162A (en) | 2003-11-19 |
Family
ID=29411626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03121530 Pending CN1456162A (en) | 2003-04-01 | 2003-04-01 | Injection of leucovorin calcium and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1456162A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229167B (en) * | 2008-02-21 | 2011-08-24 | 齐建新 | Method of preparing sodium levofolinate and applications thereof on preparing tumour-curing medicines |
| CN102178681A (en) * | 2011-03-25 | 2011-09-14 | 江苏奥赛康药业有限公司 | Injection calcium folinate composite and preparation method thereof |
| CN108392470A (en) * | 2018-04-13 | 2018-08-14 | 健进制药有限公司 | A kind of production technology of injection Calcium Levofolinate freeze-dried powder |
| CN110314146A (en) * | 2019-08-11 | 2019-10-11 | 天津乾丰瑞科技有限公司 | A kind of pharmaceutical composition containing active constituent Calcium Levofolinate |
-
2003
- 2003-04-01 CN CN 03121530 patent/CN1456162A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229167B (en) * | 2008-02-21 | 2011-08-24 | 齐建新 | Method of preparing sodium levofolinate and applications thereof on preparing tumour-curing medicines |
| CN102178681A (en) * | 2011-03-25 | 2011-09-14 | 江苏奥赛康药业有限公司 | Injection calcium folinate composite and preparation method thereof |
| CN102178681B (en) * | 2011-03-25 | 2013-05-08 | 江苏奥赛康药业股份有限公司 | Injection calcium folinate composite and preparation method thereof |
| CN108392470A (en) * | 2018-04-13 | 2018-08-14 | 健进制药有限公司 | A kind of production technology of injection Calcium Levofolinate freeze-dried powder |
| CN108392470B (en) * | 2018-04-13 | 2019-09-10 | 健进制药有限公司 | A kind of production technology of injection Calcium Levofolinate freeze-dried powder |
| CN110314146A (en) * | 2019-08-11 | 2019-10-11 | 天津乾丰瑞科技有限公司 | A kind of pharmaceutical composition containing active constituent Calcium Levofolinate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102258472A (en) | Combined medicament formulation of cefuroxime sodium liposome, preparation method and applications thereof | |
| CA3157550C (en) | Injectable psychoactive alkaloid composition and preparation thereof | |
| CN105078905B (en) | A kind of preparation method of doxycycline hydrochloride for injection freeze drying powder injection | |
| CN102512378A (en) | Stable and safe oxiracetam pharmaceutical composition for injection | |
| US20190133953A1 (en) | Preparation Method of Azacitidine for Injection | |
| CN101513387A (en) | Esomeprazole magnesium injection liquid | |
| CN102038651B (en) | Ropivacaine mesylate freeze-dried powder injection | |
| CN102276533B (en) | New ozagrel sodium compound and medicinal composition thereof | |
| CN102283808A (en) | Azithromycin liposome combined medicament and preparation method thereof | |
| CN1456162A (en) | Injection of leucovorin calcium and its preparing method | |
| CN101940557B (en) | Method for preparing fat-soluble vitamin freeze-dried powder injection | |
| CN102367229B (en) | Ethylenediamine diaceturate compound and pharmaceutical composition thereof | |
| CN103494779B (en) | Andrographolide powder preparation for injection and preparation method thereof | |
| CN1732972A (en) | Dextran for injection and method for preparing the same | |
| CN101444479A (en) | Lapatinib injection and preparation method thereof | |
| CN1161121C (en) | Alkaloid of matrine category utilized for mainline and its preparation method | |
| CN1230175C (en) | Ligustrazine hydrochloride freeze-dried preparation for injection and its preparing method | |
| CN106924195B (en) | Freeze-drying process of paclitaxel liposome composition for injection | |
| CN101143144A (en) | Milrinone lactate freezing-dried powder injection and preparation method thereof | |
| CN105213326A (en) | A kind of preparation method of clindamycin phosphate for injection lyophilized powder | |
| CN101023938A (en) | Atenolol frozen dry injecta and preparing method | |
| CN1074278C (en) | Preparation of bacteria-free freezing-dried prostaglandin E1 powder injection | |
| CN1568996A (en) | Freeze dried formulation of ciprofloxacin hydrochloride and its preparation method | |
| CN102133201B (en) | Faropenem sodium freeze-dried powder injection | |
| CN116421569B (en) | Parafaxib sodium pharmaceutical composition for injection and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |