CN103127007A - Sodium glycididazole composition and preparation method thereof - Google Patents
Sodium glycididazole composition and preparation method thereof Download PDFInfo
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- CN103127007A CN103127007A CN2013100811581A CN201310081158A CN103127007A CN 103127007 A CN103127007 A CN 103127007A CN 2013100811581 A CN2013100811581 A CN 2013100811581A CN 201310081158 A CN201310081158 A CN 201310081158A CN 103127007 A CN103127007 A CN 103127007A
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- mannitol
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Abstract
The invention relates to the field of a pharmaceutical preparation, and particularly relates to a sodium glycididazole composition and a preparation method thereof. The sodium glycididazole composition includes sodium glycididazole, mannitol, and sodium bicarbonate. The preparation method comprises the steps of dissolving mannitol by injection water under room temperature to obtain mannitol solution; slowly adding the sodium glycididazole material to the mannitol solution, slowly agitating and dissolving to obtain soup, dissolving the sodium bicarbonate by the injection water to obtain the sodium bicarbonate solution; adjusting the pH of the soup to 6.8-7.8 by the sodium bicarbonate solution, supplying the injection water, filtering, bulking, freeze-drying and capping. The sodium glycididazole composition not only is simple in prescription and process, but also is stable in preparation, reduces the cost, is suitable for industrial production, greatly avoids and reduces the loss of the sodium glycididazole, and ensures development of the pesticide effect.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of CMNa composition and method of making the same.
Background technology
The sickness rate of malignant tumor increases year by year, the serious threat human health.Radiotherapy is one of Main Means of modern oncotherapy, but approximately contains the anoxic cell of 10-50% in malignant tumor, and they have radiation resistance, has seriously affected the effect of tumor radiotherapy.Therefore, the raising ray is very important to the selectivity of tumor tissues anoxic cell.Tumor radiotherapy enhanced sensitivity medicine is to improve the tumor tissues anoxic cell radiation sensitive is effectively protected a Normocellular class medicine, can significantly improve the short term effect of tumor radiotherapy, improves cure rate.
CMNa is the novel nitro glyoxaline compound that obvious radiosensitizing effect is arranged, also that the enhanced sensitivity compound is treated in unique formal put (change) in clinical independent application both at home and abroad at present, present domestic clinical practice is more general, it can improve the sensitivity of anoxic cell to ray in the entity tumor tissue, and normal tissue has no significant effect.CMNa chemistry N by name, two [(2-methyl-5-nitro-1H-imidazoles-1-yl)-ethoxy carbonyl methyl]-Glycine sodium trihydrates of N-, structure has two metronidazole groups and three carbonyls in its structure as shown in formula I.
Formula I
CMNa is less stable in aqueous solution, facile hydrolysis and also unstable to heat.In order to solve stability problem, preparation should adopt cryodesiccated preparation technology to improve the stability of medicine.Present disclosed lyophilized formulations and preparation method thereof is heated to 40 ℃ of left and right for getting distilled water, adds freeze-dried excipient mannitol and principal agent CMNa, is stirred to dissolving, adds active carbon, and is standing after mixing, filters NaHCO
3Regulate pH to 7.0 ~ 7.5, microporous filter membrane filters, packing, move into freeze drier and carry out lyophilizing, get off-white color to flaxen loose block or Powdered finished product [Qian Fang etc., the preparation of CMNa freeze dried injection and assay thereof, Chinese Pharmaceutical Journal, 1996,31(11): 685-686].There are following defective in this Glycididazole composition of sodium and preparation method:
(1) freeze-dried excipient mannitol and principal agent adopt 40 ℃ of distilled water dissolvings, cause the loss of principal agent CMNa, affect drug effect;
(2) mannitol and CMNa are joined in distilled water simultaneously, not only cause CMNa not dissolve at ambient temperature, and cause the loss of CMNa, affect therapeutic effect;
(3) need distilled water is heated and temperature control, be unfavorable for suitability for industrialized production.
The present invention is directed to defects, composition, component proportion and preparation method by the research CMNa, a kind of Glycididazole composition of sodium of special ratios is provided, this pharmaceutical composition is not only write out a prescription simple with technique, reduce costs and suitable suitability for industrialized production, and preparation stabilization, avoid greatly and reduced the loss of CMNa, guaranteed the performance of drug effect.
Summary of the invention
The invention provides a kind of Glycididazole sodium pharmaceutical composition.
Glycididazole sodium pharmaceutical composition provided by the invention comprises CMNa, mannitol and sodium bicarbonate, wherein the mass ratio of CMNa and mannitol is 1:0.2 ~ 2, the mass ratio of preferred CMNa and mannitol is 1:0.5 ~ 1, and more preferably the mass ratio of CMNa and mannitol is 1:0.8.
The present invention also provides a kind of preparation method of Glycididazole sodium pharmaceutical composition.
The preparation method of Glycididazole sodium pharmaceutical composition provided by the invention is: mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, slowly add the Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 6.8 ~ 7.8 with sodium bicarbonate solution, add water for injection, filter, fill, lyophilizing is rolled lid and get final product.
The preparation method of Glycididazole sodium pharmaceutical composition provided by the invention is: mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, slowly add the Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, wherein the mass ratio of CMNa and mannitol is 1:0.2 ~ 2, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.0 ~ 7.5 with 10% sodium bicarbonate solution, add water for injection, filter, fill, lyophilizing is rolled lid and get final product.
The preparation method of Glycididazole sodium pharmaceutical composition provided by the invention is: mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, slowly add the Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, wherein the mass ratio of CMNa and mannitol is 1:0.5 ~ 1, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.4 with 10% sodium bicarbonate solution, add water for injection, filter, fill, lyophilizing is rolled lid and get final product.
The preparation method of Glycididazole sodium pharmaceutical composition provided by the invention is: mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, slowly add the Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, wherein the mass ratio of CMNa and mannitol is 1:0.8, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.4 with 10% sodium bicarbonate solution, add water for injection, filter, fill, lyophilizing is rolled lid and get final product.
The present invention is by the mass ratio of restriction CMNa and mannitol and first use room temperature water for injection to dissolve in mannitol, again the Glycididazole sodium raw materials is joined the method for dissolving in mannitol solution, guaranteed CMNa dissolving at ambient temperature, not only reduced the loss of active component content in the medicinal liquid process for preparation, guaranteed the performance of drug effect, and the lyophilizing liquid for the treatment of that has guaranteed to prepare keeps pH value stable in long-time at ambient temperature, guaranteed the feasibility of suitability for industrialized production.
The specific embodiment
Embodiment 1
50g mannitol is dissolved to get mannitol solution with the 2000ml water for injection under room temperature condition, slowly add 250g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.2 with 10% sodium bicarbonate solution, add water for injection to 2500ml, filter, fill is made 1000 bottles, and lyophilizing is rolled lid and get final product.
Embodiment 2
250g mannitol is dissolved to get mannitol solution with the 4200ml water for injection under room temperature condition, slowly add 500g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.0 with 10% sodium bicarbonate solution, add water for injection to 5000ml, filter, fill is made 2000 bottles, and lyophilizing is rolled lid and get final product.
Embodiment 3
500g mannitol is dissolved to get mannitol solution with the 2100ml water for injection under room temperature condition, slowly add 250g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.5 with 10% sodium bicarbonate solution, add water for injection to 2500ml, filter, fill is made 1000 bottles, and lyophilizing is rolled lid and get final product.
Embodiment 4
500g mannitol is dissolved to get mannitol solution with the 4200ml water for injection under room temperature condition, slowly add 500g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.8 with 10% sodium bicarbonate solution, add water for injection to 5000ml, filter, fill is made 2000 bottles, and lyophilizing is rolled lid and get final product.
Embodiment 5
1500g mannitol is dissolved to get mannitol solution with the 8400ml water for injection under room temperature condition, slowly add 1000g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 6.8 with 10% sodium bicarbonate solution, add water for injection to 10000ml, filter, fill is made 4000 bottles, and lyophilizing is rolled lid and get final product.
Embodiment 6
200g mannitol is dissolved to get mannitol solution with the 2100ml water for injection under room temperature condition, slowly add 250g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.5 with 10% sodium bicarbonate solution, add water for injection to 2500ml, filter, fill is made 1000 bottles, and lyophilizing is rolled lid and get final product.
Embodiment 7
100g mannitol is dissolved to get mannitol solution with the 2100ml water for injection under room temperature condition, slowly add 250g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.4 with 10% sodium bicarbonate solution, add water for injection to 2500ml, filter, fill is made 1000 bottles, and lyophilizing is rolled lid and get final product.
Embodiment 8
200g mannitol is dissolved to get mannitol solution with the 2100ml water for injection under room temperature condition, slowly add 250g Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.4 with 10% sodium bicarbonate solution, add water for injection to 2500ml, filter, fill is made 1000 bottles, and lyophilizing is rolled lid and get final product.
Test example 1 CMNa is treated lyophilizing liquid stability test
According to the method in the embodiment of the present invention 8 make 3 batches through filtering but not yet the finished product of lyophilizing be placed under the condition of room temperature and room light, preserved 10 hours, investigate CMNa and treat appearance character, pH value and the Glycididazole sodium content of lyophilizing liquid, result is as shown in table 1.
CMNa content assaying method: measure according to high performance liquid chromatography (2010 editions appendix VD of Chinese Pharmacopoeia).
Chromatographic condition and system suitability test: be filler with octadecylsilane chemically bonded silica; Take second eyeball-0.05mol/L ammonium acetate (transferring pH to 7.1 with 10% sodium hydroxide solution) (15:85) solution as mobile phase, detect wavelength 316nm.Number of theoretical plate should be not less than 1200 by Glicididazole peak calculating.Measure: precision takes CMNa reference substance 25mg, puts in the 50ml brown bottle, is diluted to scale with flowing to mix, and shakes up, in contrast product solution; Precision measures test sample 5ml and puts in the 500ml brown bottle, adds mobile phase and is diluted to scale, shakes up, as need testing solution; Get respectively reference substance solution and need testing solution 20 μ l injection high performance liquid chromatographs, record chromatogram.Press external standard method with calculated by peak area, and get final product.
Table 1 CMNa is treated appearance character, pH value and the Glycididazole sodium content of lyophilizing liquid
As can be seen from Table 1, CMNa is treated lyophilizing liquid, and not only pH value is stable in 10 hours, SOLUTION PROPERTIES is stable, there is not material to separate out, and the stable content of principal agent CMNa in medicinal liquid, thereby treats the fill of lyophilizing liquid and enter the lyophilizing program to provide the sufficient time for CMNa, guaranteed the feasibility of suitability for industrialized production, be conducive to suitability for industrialized production, and avoided the loss of principal agent CMNa, guaranteed the performance of drug effect.
Claims (7)
1. a Glycididazole sodium pharmaceutical composition, is characterized in that comprising CMNa, mannitol and sodium bicarbonate, and wherein the mass ratio of CMNa and mannitol is 1:0.2 ~ 2.
2. Glycididazole sodium pharmaceutical composition according to claim 1, the mass ratio that it is characterized in that CMNa and mannitol is 1:0.5 ~ 1.
3. Glycididazole sodium pharmaceutical composition according to claim 2, the mass ratio that it is characterized in that CMNa and mannitol is 1:0.8.
4. the preparation method of a Glycididazole sodium pharmaceutical composition, it is characterized in that mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, the Glycididazole sodium raw materials is slowly added in mannitol solution, and low rate mixing dissolves to get medicinal liquid, sodium bicarbonate is dissolved to get sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 6.8 ~ 7.8 with sodium bicarbonate solution, add water for injection, filter fill, lyophilizing is rolled lid and get final product.
5. preparation method according to claim 4, it is characterized in that mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, slowly add the Glycididazole sodium raw materials in mannitol solution, and low rate mixing dissolves to get medicinal liquid, wherein the mass ratio of CMNa and mannitol is 1:0.2 ~ 2, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.0 ~ 7.5 with 10% sodium bicarbonate solution, add water for injection, filter, fill, lyophilizing is rolled lid and get final product.
6. preparation method according to claim 5, it is characterized in that mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, the Glycididazole sodium raw materials is slowly added in mannitol solution, and low rate mixing dissolves to get medicinal liquid, wherein the mass ratio of CMNa and mannitol is 1:0.5 ~ 1, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.4 with 10% sodium bicarbonate solution, add water for injection, filter, fill, lyophilizing is rolled lid and get final product.
7. preparation method according to claim 6, it is characterized in that mannitol is dissolved to get mannitol solution with the water for injection under room temperature condition, the Glycididazole sodium raw materials is slowly added in mannitol solution, and low rate mixing dissolves to get medicinal liquid, wherein the mass ratio of CMNa and mannitol is 1:0.8, sodium bicarbonate is dissolved to get 10% sodium bicarbonate solution with water for injection, regulate medicinal liquid pH to 7.4 with 10% sodium bicarbonate solution, add water for injection, filter, fill, lyophilizing is rolled lid and get final product.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103494811A (en) * | 2013-10-09 | 2014-01-08 | 南京绿叶思科药业有限公司 | Sodium glycididazole composition and preparation method thereof |
| CN108685859A (en) * | 2017-04-12 | 2018-10-23 | 苏州特瑞药业有限公司 | One kind preparation of sodium containing Glycididazole and preparation method thereof |
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| CN1769273A (en) * | 2005-05-12 | 2006-05-10 | 济南时代医药科技有限公司 | Meglumine glycididazole and its preparation method and uses as synergist of radiochemical therapy |
| CN101265233A (en) * | 2007-03-16 | 2008-09-17 | 南京莱因医药科技有限公司 | Radiation and chemotherapy sensitizing agent-glucosamine glycididazole and preparation method thereof |
| CN101514189A (en) * | 2008-02-18 | 2009-08-26 | 杨喜鸿 | Glycin diazole tromethamine compound as well as preparation method and medicament application thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1769273A (en) * | 2005-05-12 | 2006-05-10 | 济南时代医药科技有限公司 | Meglumine glycididazole and its preparation method and uses as synergist of radiochemical therapy |
| CN101265233A (en) * | 2007-03-16 | 2008-09-17 | 南京莱因医药科技有限公司 | Radiation and chemotherapy sensitizing agent-glucosamine glycididazole and preparation method thereof |
| CN101514189A (en) * | 2008-02-18 | 2009-08-26 | 杨喜鸿 | Glycin diazole tromethamine compound as well as preparation method and medicament application thereof |
Non-Patent Citations (1)
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| 钱方等: "甘氨双唑钠冻干注射剂的制备及其含量测定", 《中国药学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103494811A (en) * | 2013-10-09 | 2014-01-08 | 南京绿叶思科药业有限公司 | Sodium glycididazole composition and preparation method thereof |
| CN103494811B (en) * | 2013-10-09 | 2014-09-03 | 南京绿叶思科药业有限公司 | Sodium glycididazole composition and preparation method thereof |
| CN108685859A (en) * | 2017-04-12 | 2018-10-23 | 苏州特瑞药业有限公司 | One kind preparation of sodium containing Glycididazole and preparation method thereof |
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| CN103127007B (en) | 2013-11-06 |
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