CN108078920B - Preparation process of stable breviscapine injection - Google Patents
Preparation process of stable breviscapine injection Download PDFInfo
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- CN108078920B CN108078920B CN201810163939.8A CN201810163939A CN108078920B CN 108078920 B CN108078920 B CN 108078920B CN 201810163939 A CN201810163939 A CN 201810163939A CN 108078920 B CN108078920 B CN 108078920B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Abstract
The invention discloses a preparation process of a stable breviscapine injection, which comprises the following steps: adding disodium ethylene diamine tetraacetate into a small part of injection water with a preparation amount, adding breviscapine, adding a proper amount of sodium bicarbonate solution to completely dissolve the raw materials to be clear, primarily adjusting the pH of the liquid medicine to 6.0-7.2 by using hydrochloric acid solution or phosphate buffer salt solution, refrigerating at low temperature, filtering the refrigerated liquid medicine by using a cylindrical filter, performing ultrafiltration by using an ultrafilter, and supplementing the injection water to the full amount according to the content of the ultrafiltered liquid medicine; adjusting pH of the medicinal liquid to 6.0-7.0 with hydrochloric acid solution or phosphate buffer solution, fine filtering with filter, bottling, and sterilizing; the prepared breviscapine injection meets the standard requirements through 6-month accelerated stability test and 36-month long-term stability test on the premise of not additionally adding auxiliary materials except breviscapine and disodium ethylenediamine tetraacetic acid of a standard prescription (with the standard number of WS 3-B-3822-98).
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a stable preparation process of breviscapine injection.
Background
The breviscapine injection is prepared by dissolving 0.26g disodium ethylene diamine tetraacetate in 280ml water for injection, adding breviscapine 1g, stirring to suspend, adding appropriate amount of sodium bicarbonate, stirring to pH7-7.5, stirring to dissolve breviscapine, adding water for injection to 400ml, adding activated carbon 0.1% of the solution volume, stirring for 20 min, removing carbon, fine filtering, packaging after semi-finished product inspection, sterilizing with steam at 100 deg.C for 15 min, testing with lamp, and packaging; or dissolving 1g disodium edetate in 700ml water for injection, adding 4g breviscapine, and making into 1000ml injection by the same method. The product contains breviscapine and scutellarin (C)21H18O12) Calculated, should be 95.0-105.0% of the identified amount.
At present, breviscapine injection on the market generally has the defects of unstable quality, continuously reduced content in an effective period, darkened color, and unqualified visible foreign matters such as precipitation, white spots, white blocks and the like.
In the prior art, Chinese patent CN 106214629A discloses that malic acid and sodium malate are used as pH regulators to regulate the pH to 4-6, and the breviscapine is separated out under the condition of pH below 6 through experiments, so that the normal production cannot be ensured. The Chinese patent CN 102198092A uses anhydrous sodium sulfite in the prescription, during the production process, after breviscapine is dissolved, water for injection is added to 1000ml, the pH value is adjusted to 6-7 by hydrochloric acid, the preparation solution is ultrafiltered by a 1000-class 10000 molecular weight ultrafilter, the filtrate is filtered by a 0.22um filter, nitrogen is filled for encapsulation, and sterilization is carried out for 15 minutes at 121 ℃. The patent firstly uses anhydrous sodium sulfite except the standard, secondly, the liquid medicine is ultrafiltered by a 1000-10000 molecular weight ultrafilter after being prepared to the end point of 1000ml, and the ultrafilter can also greatly adsorb breviscapine when intercepting macromolecular substances such as protein, amino acid, resin, heat source and the like, so that the ultrafilter is not suitable for being used for filtering. Chinese patent CN 1476840A discloses that pH is adjusted to 4.5-6.5 by using dilute acetic acid, hydrochloric acid, citric acid, boric acid, etc., breviscapine is precipitated under the condition of pH below 6 through experiments, normal production can not be ensured, and substances except for standards, such as L-arginine, glycerol, ethanol, etc., are also used. Chinese patent CN 1861087a discloses that the whole process is protected by nitrogen filling, under the protection of nitrogen filling, scutellarin is added into injection water with partial dosage (such as 50%), bicarbonate solution is added until completely dissolved, appropriate amount of stabilizer or combination thereof (including EDTA-2Na, carbonate or bicarbonate, vitamin C, and polysorbate 80, the above stabilizers can be used alone or in combination), stirring rod is used for dissolving, water is added to full dosage, ph is adjusted to 6.5-7.5 with sodium bicarbonate solution, fine filtration, encapsulation, and sterilization. In the above patents, some have unrealistic performance in the technical implementation link, some have added other auxiliary materials beyond the standard, and product quality can't be guaranteed, and medicine security is unknown.
Therefore, how to create a stable preparation process of breviscapine injection without adding other auxiliary materials except for the standard, and with guaranteed product quality and drug safety becomes an object of great improvement in the industry at present.
Disclosure of Invention
The invention aims to solve the technical problem of providing a stable preparation process of breviscapine injection, which does not need to add other auxiliary materials except for standards, and ensures the product quality and the medicine safety.
In order to solve the technical problems, the invention adopts the following technical scheme:
a preparation process of a stable breviscapine injection comprises the following steps:
adding disodium ethylene diamine tetraacetate into a small part of injection water with a preparation amount, adding breviscapine, adding a proper amount of sodium bicarbonate solution to completely dissolve the raw materials to be clear, primarily adjusting the pH of the liquid medicine to 6.0-7.2 by using hydrochloric acid solution or phosphate buffer salt solution, refrigerating at low temperature, filtering the refrigerated liquid medicine by using a cylindrical filter, performing ultrafiltration by using an ultrafilter, and supplementing the injection water to the full amount according to the content of the ultrafiltered liquid medicine; adjusting pH of the medicinal liquid to 6.0-7.0 with hydrochloric acid solution or phosphate buffer solution, fine filtering with filter, bottling, and sterilizing; wherein, the injection adopts the standard prescription dosage (the standard number is WS 3-B-3822-98): every 1000ml of injection comprises 1g of disodium edetate and 4g of breviscapine; or every 400ml injection comprises 0.26g of disodium edetate and 1g of breviscapine.
Further preferably, disodium edetate is added to 15-30% of the formulated amount of water for injection.
Further preferably, the liquid medicine is refrigerated at a low temperature of 0-10 ℃ for 20-30 hours.
More preferably, the refrigerated medical liquid is filtered by a 0.3-0.5um cylinder filter and then is ultrafiltered by an ultrafilter with 8000-10000 molecular weight.
Further preferably, the pH is adjusted twice and then fine-filtered with a 0.22um filter.
Further preferably, the filter is filled with nitrogen for encapsulation after fine filtration.
Further preferably, the potting is a polypropylene plastic ampoule, a polyethylene plastic ampoule, a low borosilicate glass ampoule or a medium borosilicate glass ampoule.
Further preferably, sterilization is carried out at 105-115 ℃ for 10-20 minutes.
By adopting the technical scheme, the invention at least has the following advantages:
1. in the invention, in the aspect of material use, no additional auxiliary materials except breviscapine and disodium edetate are added into a standard prescription (with the standard number of WS3-B-3822-98), because for an injection product, in order to ensure the safety of the injection product, the fewer the auxiliary materials are used, the safer the auxiliary materials are; in the preparation process, the invention defines that the dissolved liquid medicine needs to be refrigerated to separate impurities, large impurities are removed by barrel filtration, and the ultrafiltration plays roles in intercepting macromolecular substances, heat sources and the like. The preparation process does not need to use active carbon with the function of adsorbing impurities, can well control the heat source and endotoxin of the product only by using ultrafiltration of an ultrafilter, and avoids the defect that the active carbon is difficult to control and cause pollution due to large dust and poor production process control.
2. The invention firstly adds the disodium ethylene diamine tetraacetate into a small part of injection water with the preparation amount, preferably 15-30%, prepares concentrated liquor, adopts ultrafiltration on the concentrated liquor, and is mainly based on the adsorbability of materials of an ultrafilter, and the content of the liquor is reduced to different degrees after the liquor is ultrafiltered by the ultrafilters with different molecular weights, so that the ultrafiltration on the concentrated liquor is safer and controllable compared with the final liquor ultrafiltration, and the process is ensured to be reproducible. The amount of water for dilution can be calculated according to the content of the liquid medicine after ultrafiltration and the content of the finished liquid medicine expected to be achieved, so that the content of the finished product is better controlled within a standard range.
3. According to the invention, the pH of the liquid medicine is adjusted for the second time before encapsulation after ultrafiltration, and the applicant finds that the pH of the liquid medicine can rise by 0.2-0.5 in the ultrafiltration process according to long-term production tests, and the analysis reason is that sodium bicarbonate is contained in the prescription, and the pH of a sodium bicarbonate solution can rise under the oscillation condition, so that the pH of the final product can reach 7.5 or more, and the stability of the product can be influenced. Therefore, the process of the invention ensures that the maximum pH of the liquid medicine is about 7 after the ultrafiltration is finished and before the encapsulation, thereby improving the stability of the product.
4. The invention defines the liquid medicine encapsulating material and has good encapsulating effect.
5. Through the accelerated stability test of 6 months and the test investigation of the stability test of 36 months in term, the key index characters, pH, content, related substances, insoluble particles and visible foreign matters all meet the standard requirements.
Detailed Description
The invention adjusts the pH value by using hydrochloric acid or phosphate buffer salt to adjust the solution without adding any auxiliary materials except breviscapine and disodium ethylene diamine tetraacetate of a standard prescription, and the concentrated prepared liquid medicine is refrigerated, ultrafiltered, adjusted in pH value again, fine filtered, encapsulated and sterilized.
The preparation process of the injection comprises the following steps: adding disodium ethylene diamine tetraacetate into a small part of injection water with a preparation amount, adding breviscapine, adding a proper amount of sodium bicarbonate solution to completely dissolve the raw materials to be clear, primarily adjusting the pH of the liquid medicine to 6.0-7.2 by using hydrochloric acid solution or phosphate buffer salt solution, refrigerating at low temperature, filtering the refrigerated liquid medicine by using a cylindrical filter, performing ultrafiltration by using an ultrafilter, and supplementing the injection water to the full amount according to the content of the ultrafiltered liquid medicine; adjusting pH of the medicinal liquid to 6.0-7.0 with hydrochloric acid solution or phosphate buffer solution, fine filtering with filter, bottling, and sterilizing; wherein, the injection adopts the following standard prescription dosage: every 1000ml of injection comprises 1g of disodium edetate and 4g of breviscapine; or every 400ml injection comprises 0.26g of disodium edetate and 1g of breviscapine.
Preferably, the preparation process of the injection of the invention is as follows: adding disodium ethylene diamine tetraacetate into 15-30% injection water, adding breviscapine, adding sodium bicarbonate solution to dissolve the raw materials completely to clarify, adjusting pH of the liquid medicine to 6.0-7.2 with hydrochloric acid or phosphate buffer salt solution, refrigerating the liquid medicine at 0-10 deg.C for 20-30 hr, filtering the refrigerated liquid medicine with 0.3-0.5 μm cylindrical filter, ultrafiltering with 8000-10000 molecular ultrafilter, supplementing water for injection to full amount according to the content of the ultrafiltered liquid medicine, adjusting pH of the liquid medicine to 6.0-7.0 with hydrochloric acid or phosphate buffer salt solution, fine filtering with 0.22 μm filter, filling nitrogen gas, bottling, optionally using polypropylene ampoule, polyethylene plastic ampoule, low borosilicate glass ampoule or medium borosilicate glass ampoule, sterilizing at 105-115 deg.C for 10-20 min, and (5) detecting leakage and performing lamp inspection to obtain the product.
The following is a detailed description of specific examples.
The first prescription is as follows: 100L injection
Breviscapine 400g
Ethylene diamine tetraacetic acid 100g
Example 1:
dissolving disodium ethylene diamine tetraacetate in 15L of water for injection, adding breviscapine, stirring to suspend, adding a proper amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 6 by using a hydrochloric acid solution with a certain concentration, refrigerating the liquid medicine for 20 hours at 0 ℃, filtering the refrigerated liquid medicine by using a 0.3um cylindrical filter, performing ultrafiltration by using an ultrafilter with a molecular weight of 8000, supplementing the water for injection to the full amount according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 6 by using the hydrochloric acid solution with a certain concentration, performing fine filtration by using a 0.22um filter, filling nitrogen, filling, encapsulating, using a polyethylene plastic ampoule, sterilizing at 105 ℃ for 20 minutes, detecting leakage, and performing light inspection to obtain the injection.
Example 2:
dissolving disodium ethylene diamine tetraacetate in 30L of water for injection, adding breviscapine, stirring to suspend, adding an appropriate amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 6.5 by using phosphate buffer salt solution with a certain concentration, refrigerating the liquid medicine for 25 hours at 6 ℃, filtering the refrigerated liquid medicine by using a 0.3um cylindrical filter, performing ultrafiltration by using an ultrafilter with a molecular weight of 8000, supplementing injection water to the full amount according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 6.5 by using phosphate buffer salt solution with a certain concentration, performing fine filtration by using a 0.22um filter, filling nitrogen into the liquid medicine, filling and sealing the liquid medicine by using a low borosilicate glass ampoule, sterilizing at 110 ℃ for 15 minutes, detecting leakage, and performing light inspection to obtain the breviscapine.
Example 3:
dissolving disodium ethylene diamine tetraacetate in 20L of water for injection, adding breviscapine, stirring to suspend, adding a proper amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 7.2 by using phosphate buffer salt solution with a certain concentration, refrigerating the liquid medicine for 25 hours at 10 ℃, filtering the refrigerated liquid medicine by using a 0.5-micron cylindrical filter, performing ultrafiltration by using an ultrafiltration filter with 10000 molecular weight, supplementing injection water to full dose according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 7 by using phosphate buffer salt solution with a certain concentration, performing fine filtration by using a 0.22-micron filter, filling and sealing by filling nitrogen, filling and sealing a borosilicate glass ampoule in use, sterilizing at 115 ℃ for 10 minutes, detecting leakage, and performing light inspection to obtain the injection.
Example 4:
dissolving disodium ethylene diamine tetraacetate in 25L of water for injection, adding breviscapine, stirring to suspend, adding an appropriate amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 6.2 by using a hydrochloric acid solution with a certain concentration, refrigerating the liquid medicine for 30 hours at 8 ℃, filtering the refrigerated liquid medicine by using a 0.5-micron cylindrical filter, performing ultrafiltration by using an ultrafilter with a 10000-molecular weight, supplementing the water for injection to the full amount according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 7 by using a hydrochloric acid solution with a certain concentration, performing fine filtration by using a 0.22-micron filter, filling nitrogen, filling, sealing, using a polypropylene plastic ampoule, sterilizing at 105 ℃ for 20 minutes, detecting leakage, and performing light inspection to obtain the injection.
And a second prescription: 80L injection
Breviscapine 200g
Ethylene diamine tetraacetic acid 52g
Example 1:
dissolving disodium ethylene diamine tetraacetate in 12L of water for injection, adding breviscapine, stirring to suspend, adding an appropriate amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 6 by using phosphate buffer salt solution with a certain concentration, refrigerating the liquid medicine for 20 hours at 0 ℃, filtering the refrigerated liquid medicine by using a 0.3um cylindrical filter, performing ultrafiltration by using an ultrafilter with a molecular weight of 8000, supplementing water for injection to full amount according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 6 by using hydrochloric acid solution with a certain concentration, performing fine filtration by using a 0.22um filter, filling nitrogen, filling, sealing, using a polyethylene plastic ampoule, sterilizing at 105 ℃ for 20 minutes, detecting leakage, and performing light inspection to obtain the injection.
Example 2:
dissolving disodium ethylene diamine tetraacetate in 18L of water for injection, adding breviscapine, stirring to suspend, adding an appropriate amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 6.5 by using a hydrochloric acid solution with a certain concentration, refrigerating the liquid medicine for 25 hours at 6 ℃, filtering the refrigerated liquid medicine by using a 0.3um cylindrical filter, performing ultrafiltration by using an ultrafilter with a molecular weight of 8000, supplementing water for injection to the full amount according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 7 by using a hydrochloric acid solution with a certain concentration, performing fine filtration by using a 0.22um filter, filling nitrogen, filling and sealing a borosilicate glass ampoule in use, sterilizing at 110 ℃ for 15 minutes, detecting leakage, and performing light inspection to obtain the injection.
Example 3:
dissolving disodium ethylene diamine tetraacetate in 24L of water for injection, adding breviscapine, stirring to suspend, adding an appropriate amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 7 by using a hydrochloric acid solution with a certain concentration, refrigerating the liquid medicine for 25 hours at 10 ℃, filtering the refrigerated liquid medicine by using a 0.5um cylindrical filter, performing ultrafiltration by using an ultrafilter with 10000 molecular weight, supplementing the water for injection to full amount according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 6.5 by using a phosphate buffer salt solution with a certain concentration, performing fine filtration by using a 0.22um filter, filling nitrogen, filling, sealing, using a low borosilicate glass ampoule, sterilizing at 115 ℃ for 10 minutes, detecting leakage, and performing light inspection to obtain the injection.
Example 4:
dissolving disodium ethylene diamine tetraacetate in 18L of water for injection, adding breviscapine, stirring to suspend, adding a proper amount of sodium bicarbonate solution to completely dissolve the breviscapine, adjusting the pH of the liquid medicine to 7.2 by using phosphate buffer salt solution with a certain concentration, refrigerating the liquid medicine for 30 hours at 4 ℃, filtering the refrigerated liquid medicine by using a 0.5-micron cylindrical filter, performing ultrafiltration by using an ultrafiltration filter with a 10000-molecular weight, supplementing injection water to full amount according to the content of the ultrafiltered liquid medicine, adjusting the pH of the liquid medicine to 6 by using hydrochloric acid solution with a certain concentration, performing fine filtration by using a 0.22-micron filter, filling and sealing by using nitrogen, filling and sealing a polypropylene plastic ampoule, sterilizing at 115 ℃ for 10 minutes, detecting leakage, and performing light inspection to obtain the injection.
The samples are respectively placed for 6 months under the condition that the temperature is 40 +/-2 ℃ and the relative humidity is 75 +/-5% and 36 months under the condition that the temperature is 25 +/-2 ℃ and the relative humidity is 60 +/-10% for stability investigation, the stability is detected according to a standard method, and the key data of the stability are as follows:
table 1 recipe one example 1 stability examination results
Table 2 recipe-example 2 stability examination results
Table 3 recipe one example 3 stability study results
Table 4 recipe-example 4 stability study results
Table 5 recipe two example 1 stability examination results
Table 6 stability test results of two examples 2
Table 7 stability test results of two examples 3
Table 8 prescription two example 4 stability examination results
Through the accelerated stability test of 6 months and the test investigation of 36 months of the stability of the production period, the breviscapine injection of the invention, the property is yellow clear liquid, the content of active substances can reach more than 100%, and the content degradation speed is slower, only 0.16 percentage point (6 months) and 0.17 percentage point (36 months) are reduced at most, the pH value, visible foreign matters, insoluble particles and related substances (mainly starting materials, intermediates, polymers, side reaction products brought in the production process, degradation products in the storage process and the like) which are very critical to the stability also meet the standard regulation, and the product quality is stable.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the present invention in any way, and it will be apparent to those skilled in the art that the above description of the present invention can be applied to various modifications, equivalent variations or modifications without departing from the spirit and scope of the present invention.
Claims (8)
1. A stable preparation process of breviscapine injection is characterized by comprising the following steps:
adding disodium ethylene diamine tetraacetate into a small part of injection water with a preparation amount, adding breviscapine, adding a proper amount of sodium bicarbonate solution to completely dissolve the raw materials to be clear, primarily adjusting the pH of the liquid medicine to 6.0-7.2 by using hydrochloric acid solution or phosphate buffer salt solution, refrigerating at low temperature, filtering the refrigerated liquid medicine by using a cylindrical filter, performing ultrafiltration by using an ultrafilter, and supplementing the injection water to the full amount according to the content of the ultrafiltered liquid medicine; adjusting pH of the medicinal liquid to 6.0-7.0 with hydrochloric acid solution or phosphate buffer solution, fine filtering with filter, bottling, and sterilizing;
wherein, the injection adopts the following standard prescription dosage: every 1000ml of injection comprises 1g of disodium edetate and 4g of breviscapine; or every 400ml injection comprises 0.26g of disodium edetate and 1g of breviscapine.
2. The process for preparing a stable breviscapine injection as claimed in claim 1, wherein disodium edetate is added to 15-30% of the amount of water for injection.
3. The process for preparing a stable breviscapine injection as claimed in claim 1, wherein the liquid medicine is refrigerated at 0-10 deg.C for 20-30 hr.
4. The process for preparing a stable breviscapine injection as claimed in claim 1, wherein the refrigerated solution is filtered through a 0.3-0.5 μm cartridge filter and then ultrafiltered through an ultrafilter with molecular weight of 8000-.
5. The process for preparing a stable breviscapine injection as claimed in claim 1, wherein the pH is adjusted twice and then fine filtered with 0.22 μm filter.
6. The process for preparing a stable breviscapine injection as claimed in claim 1, wherein the filtration is carried out by filling nitrogen gas and sealing.
7. The process for preparing a stable breviscapine injection as claimed in claim 1, wherein the encapsulation is polypropylene plastic ampoule, polyethylene plastic ampoule, low borosilicate glass ampoule or medium borosilicate glass ampoule.
8. The process for preparing a stable breviscapine injection as claimed in claim 1, wherein the sterilization is carried out at 105-115 ℃ for 10-20 min.
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| CN113712910A (en) * | 2021-08-05 | 2021-11-30 | 广州市桐晖药业有限公司 | Eye drops and preparation method thereof |
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| CN101757068A (en) * | 2008-11-25 | 2010-06-30 | 天津太平洋制药有限公司 | Breviscapine frozen dry powder for injection and preparation method thereof |
| KR20130005616A (en) * | 2011-07-07 | 2013-01-16 | 주식회사 알엔에스 | Skin whitening agent |
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| CN1565465A (en) * | 2003-06-26 | 2005-01-19 | 天津药物研究院 | Injection preparation containing breviscapine active component and its preparation method |
| CN1476840A (en) * | 2003-07-15 | 2004-02-25 | 上海博泰医药科技有限公司 | Preparation method of stable fleabane extract injection |
| CN1830451B (en) * | 2005-03-08 | 2010-09-08 | 万生联合制药有限公司 | Preparation method of erigeron breviscapus glucese injection |
| CN1732970A (en) * | 2005-08-13 | 2006-02-15 | 杭州民生药业集团有限公司 | Breviscapine injection liquid and its preparing process |
| CN102198092A (en) * | 2011-05-27 | 2011-09-28 | 吉林龙泰制药股份有限公司 | Breviscapine injection and preparation method thereof |
| CN106214629A (en) * | 2016-08-09 | 2016-12-14 | 成都佳迪璐莎生物科技有限公司 | A kind of preparation method of breviscapine drug injection preparation stability compositions |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101757068A (en) * | 2008-11-25 | 2010-06-30 | 天津太平洋制药有限公司 | Breviscapine frozen dry powder for injection and preparation method thereof |
| KR20130005616A (en) * | 2011-07-07 | 2013-01-16 | 주식회사 알엔에스 | Skin whitening agent |
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