CN102836132A - Methylsulfonic acid nafamostat lyophilized powder injection - Google Patents
Methylsulfonic acid nafamostat lyophilized powder injection Download PDFInfo
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- CN102836132A CN102836132A CN2012101017937A CN201210101793A CN102836132A CN 102836132 A CN102836132 A CN 102836132A CN 2012101017937 A CN2012101017937 A CN 2012101017937A CN 201210101793 A CN201210101793 A CN 201210101793A CN 102836132 A CN102836132 A CN 102836132A
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- nafamostat
- powder injection
- acid
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- dried powder
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to the field of pharmaceutical preparation, and in particular relates to a methylsulfonic acid nafamostat lyophilized powder injection and a method for preparing the powder injection. The lyophilized powder injection consists of active ingredient methylsulfonic acid nafamostat, an excipient and a pH conditioning agent, wherein the pH conditioning agent is an organic acid or organic buffer system, the pH values of the solution before or after being lyophilized are kept in the range of 3.0-4.5 through using the pH conditioning agent, and the pharmaceutical stability is effectively maintained.
Description
Technical field
The present invention relates to the pancreatitic protease inhibitor Nafamostat Mesilate of a kind of treatment, be specifically related to freeze-dried powder injection of nafamostat mesylate and preparation method thereof.Belong to medical technical field.
Background technology
Nafamostat Mesilate is synthetic protease inhibitor.Be mainly used in the various pancreatitiss of treatment, also can be used for suffering a shock, anticoagulant, the early treatment of DIC and the treatment of autoimmune disease etc. when cardiac operation under direct vision and blood extracorporeal circulation.
The molecular formula of Nafamostat Mesilate, molecular weight, structural formula and physicochemical property are distinguished as follows:
Molecular formula: C
19H
17N
5O
22CH
4O
3S
Molecular weight: 539.58
Structural formula:
Physicochemical property: these article are white crystalline powder, be soluble in formic acid (＞1g/ml), be slightly soluble in water (4.91g/ml); Be insoluble to ethanol; Melting point is about 260 ℃ (decomposition), because it is the esters structure, in water, is prone to degrade in (especially being hot water), alkalescence and the strong acid solution; Process aqueous injection and can't satisfy storage and the stability requirement during clinical use, therefore limited its use clinically.
Summary of the invention
The invention discloses a kind of freeze-dried powder of stable Nafamostat Mesilate.
Its constituent of freeze-dried powder injection of nafamostat mesylate of the present invention is Nafamostat Mesilate, excipient and pH regulator agent, and wherein excipient is a mannitol.
The method for preparing of the freeze-dried powder of Nafamostat Mesilate is mainly taked following steps:
(1) preparating liquid: the active component Nafamostat Mesilate is added injection water (25-30 ℃) dissolving, add the mannitol stirring and make dissolving, mixing adds the injection water to ormal weight;
(2) adjust pH: the pH value that adds pH regulator agent adjusting medicinal liquid is in the 3.5-4.0 scope;
(3) depyrogenation: in the medicinal liquid of step (2), add and filter after proper amount of active carbon (temperature＜40 ℃) stirs 20min;
(4) degerming: the filtrating of step (3) is carried out degerming with germ tight filter;
(5) fill: carry out aseptic subpackaged with the control cillin bottle;
(6) lyophilizing: the medicinal liquid in the step (5) is carried out lyophilization according to preset temperature, and guarantee moisture＜2%.
The specific embodiment
Specify the present invention through specific embodiment below, embodiments of the invention are to be used to explain the present invention rather than limitation of the present invention, so the present invention is not limited to these embodiment.
Embodiment 1
The preparation process:
Preparating liquid: take by weighing recipe quantity Nafamostat Mesilate crude drug and add injection water dissolving, add recipe quantity mannitol stir make its dissolving after, add the injection water to ormal weight;
Adjust pH: it is an amount of to add the citric acid acid buffer, regulates medicinal liquid pH value 3.0-4.5.;
Depyrogenation: the injection active carbon that in above-mentioned medicinal liquid, adds cumulative volume 0.02% stirs 20min down at 40 ℃, and filtering with microporous membrane takes off charcoal; Collect filtrating;
Degerming: above-mentioned solution is carried out the malleation aseptic filtration with germ tight filter, and plug etc. adopt moist heat sterilization, and equipment such as material-compound tank, fluid reservoir, injection water pot, freeze dryer and pipeline adopt online sterilization;
Fill: above-mentioned filtrating is carried out carrying out sterile filling behind the assay;
Lyophilizing: pre-freeze stage :-45 ℃ keep 2-10h
Sublimation drying: 20 ℃/h is warming up to-15 ℃ and keeps 10-20h
Dry again: 20 ℃/h is warming up to 0 ℃ and keeps 3-10h
Being warming up to the plate temperature with 20 ℃/h at last takes out when consistent with products temperature and rolls lid, packs.
Embodiment 2
Method for preparing is with embodiment 1, and the mannitol consumption is 30g.
Embodiment 3
Method for preparing is with embodiment 1, and the mannitol consumption is 60g.
Embodiment 4
Method for preparing is with embodiment 1, and the mannitol consumption is 80g.
Embodiment 5
Method for preparing is with embodiment 1, and adding lactic acid adjusting pH value is 3.0-4.5.
Embodiment 6
Method for preparing is with embodiment 1, and adding fumaric acid adjusting medicinal liquid pH value is 3.0-4.5.
Embodiment 7
Method for preparing is with embodiment 1, and it is 3.0-4.5 that tartarize is regulated the medicinal liquid pH value.
Embodiment 8
Method for preparing is with embodiment 1, and adding succinic acid adjusting medicinal liquid pH value is 3.0-4.5.
Embodiment 9
Method for preparing is with embodiment 1, and adding glutamic acid adjusting medicinal liquid pH value is 3.0-4.5.
Embodiment 10
Method for preparing is with embodiment 1, and adding hydrochloric acid adjusting medicinal liquid pH value is 3.0-4.5.
The Nafamostat Mesilate freeze-dried powder of the foregoing description 1-10 is carried out the accelerated test investigation, and constant product quality meets the Chinese Pharmacopoeia related request as a result.
Description of drawings
Accompanying drawing is the freeze-drying curve figure of embodiment 1 described freeze-dried powder injection of nafamostat mesylate.
Claims (7)
1. a freeze-dried powder injection of nafamostat mesylate is made up of Nafamostat Mesilate, excipient, pH regulator agent, and wherein excipient is a mannitol.
2. the freeze-dried powder injection of nafamostat mesylate of claim 1 is characterized in that, wherein the weight ratio of mannitol and Nafamostat Mesilate is 1-20: 1.
3. the freeze-dried powder injection of nafamostat mesylate of claim 2 is characterized in that, wherein the weight ratio of mannitol and Nafamostat Mesilate is 4: 1.
4. the freeze-dried powder injection of nafamostat mesylate of claim 1; It is characterized in that; Wherein the pH regulator agent is one or more in citric acid, tartaric acid, hydrochloric acid, fumaric acid, succinic acid, lactic acid, acetic acid, methanesulfonic acid, Aspartic Acid, the glutamic acid, and the pH value scope of lyophilized powder redissolution back solution is 3.0-4.5.
5. the method for preparing of each freeze-dried powder injection of nafamostat mesylate in the claim 1 to 4 comprises: Nafamostat Mesilate is added the dissolving of injection water, add the mannitol dissolving; Add the injection water to ormal weight, add the pH regulator agent and regulate the medicinal liquid pH value in the 3.0-4.5 scope, add active carbon; Filter; Degerming, fill, lyophilization.
6. the method for preparing of the freeze-dried powder injection of nafamostat mesylate of claim 5 is characterized in that, the pH value scope after its lyophilization lyophilizing is redissolved is at 3.0-4.5.
7. the method for preparing of the freeze-dried powder injection of nafamostat mesylate of claim 5 is characterized in that, the temperature of its whole operation process is lower than 40 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101017937A CN102836132A (en) | 2012-04-09 | 2012-04-09 | Methylsulfonic acid nafamostat lyophilized powder injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101017937A CN102836132A (en) | 2012-04-09 | 2012-04-09 | Methylsulfonic acid nafamostat lyophilized powder injection |
Publications (1)
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|---|---|
| CN102836132A true CN102836132A (en) | 2012-12-26 |
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| CN2012101017937A Pending CN102836132A (en) | 2012-04-09 | 2012-04-09 | Methylsulfonic acid nafamostat lyophilized powder injection |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412060A (en) * | 2015-11-15 | 2016-03-23 | 北京泰德制药股份有限公司 | Nafamostat mesilate composition and preparation method thereof |
| WO2021147272A1 (en) * | 2020-01-21 | 2021-07-29 | 中国人民解放军军事科学院军事医学研究院 | Use of benzoate compound in treatment of sars-cov-2 infections |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100998580A (en) * | 2006-12-20 | 2007-07-18 | 南京科源医药技术有限公司 | Freeze-dried powder injection of nafamostat mesylate and its preparing method |
-
2012
- 2012-04-09 CN CN2012101017937A patent/CN102836132A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100998580A (en) * | 2006-12-20 | 2007-07-18 | 南京科源医药技术有限公司 | Freeze-dried powder injection of nafamostat mesylate and its preparing method |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412060A (en) * | 2015-11-15 | 2016-03-23 | 北京泰德制药股份有限公司 | Nafamostat mesilate composition and preparation method thereof |
| CN105412060B (en) * | 2015-11-15 | 2018-06-08 | 北京泰德制药股份有限公司 | A kind of Nafamostat Mesilate composition and preparation method thereof |
| WO2021147272A1 (en) * | 2020-01-21 | 2021-07-29 | 中国人民解放军军事科学院军事医学研究院 | Use of benzoate compound in treatment of sars-cov-2 infections |
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| PB01 | Publication | ||
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Application publication date: 20121226 |