CN103417568A - Glycerin fructose sodium chloride injection and preparation method thereof - Google Patents
Glycerin fructose sodium chloride injection and preparation method thereof Download PDFInfo
- Publication number
- CN103417568A CN103417568A CN2013103446908A CN201310344690A CN103417568A CN 103417568 A CN103417568 A CN 103417568A CN 2013103446908 A CN2013103446908 A CN 2013103446908A CN 201310344690 A CN201310344690 A CN 201310344690A CN 103417568 A CN103417568 A CN 103417568A
- Authority
- CN
- China
- Prior art keywords
- injection
- sodium chloride
- water
- prescription
- sterilizing
- 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.)
- Granted
Links
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 239000008354 sodium chloride injection Substances 0.000 title claims abstract description 12
- 229930091371 Fructose Natural products 0.000 title claims abstract description 11
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 title claims abstract description 11
- 239000005715 Fructose Substances 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 235000011187 glycerol Nutrition 0.000 title abstract 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000008215 water for injection Substances 0.000 claims abstract description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 16
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 239000011780 sodium chloride Substances 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 239000004695 Polyether sulfone Substances 0.000 claims abstract description 4
- 239000013505 freshwater Substances 0.000 claims abstract description 4
- 229920006393 polyether sulfone Polymers 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 230000001954 sterilising effect Effects 0.000 claims description 24
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 9
- 229930195725 Mannitol Natural products 0.000 claims description 9
- 230000001186 cumulative effect Effects 0.000 claims description 9
- 238000005304 joining Methods 0.000 claims description 9
- 239000000594 mannitol Substances 0.000 claims description 9
- 235000010355 mannitol Nutrition 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000009826 distribution Methods 0.000 claims description 3
- 238000005070 sampling Methods 0.000 claims description 3
- 238000004659 sterilization and disinfection Methods 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- NOEGNKMFWQHSLB-UHFFFAOYSA-N 5-hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 abstract description 7
- RJGBSYZFOCAGQY-UHFFFAOYSA-N hydroxymethylfurfural Natural products COC1=CC=C(C=O)O1 RJGBSYZFOCAGQY-UHFFFAOYSA-N 0.000 abstract description 7
- 239000003381 stabilizer Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 2
- 238000005259 measurement Methods 0.000 abstract description 2
- 238000002156 mixing Methods 0.000 abstract 4
- 238000002835 absorbance Methods 0.000 abstract 2
- 238000007865 diluting Methods 0.000 abstract 2
- 238000001914 filtration Methods 0.000 abstract 1
- 239000007924 injection Substances 0.000 abstract 1
- 238000002347 injection Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000001502 supplementing effect Effects 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 4
- -1 aldehyde compound Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides glycerin fructose sodium chloride injection and a preparation method thereof and belongs to the technical field of medicine. The invention mainly solves the problem that, in the prior art, absorbance exceeds standard during measurement of 5-hydroxymethyl furfural. The glycerin fructose sodium chloride injection is characterized in that 1,000 ml of the prescription comprises the following raw and auxiliary materials: 99 to 101 g of glycerin, 49 to 51 g of fructose and 8 to 10 g of sodium chloride, and fresh water for injection is added until the volume is 1,000 ml. The preparation method comprises the following steps: sequentially adding the sodium chloride, the glycerin and the fructose according to the prescription quantity into a thick mixing tank with the water for injection which is 30 percent of the total volume of the prescription; opening the liquid outlet of the thick mixing tank and the liquid inlet of a diluting mixing tank after the raw materials are completely dissolved; putting the mixture into the diluting mixing tank; supplementing the mixture with water for injection until the volume is 99 percent and adjusting the pH value to be 3.8 to 4.2; filtering by a terminal filter with a 0.22-micron polyether sulfone filter element and filling to obtain the injection, wherein a stabilizing agent is not added into the product and the absorbance of the 5-hydroxymethyl furfural is less than 0.6.
Description
Technical field
The invention belongs to field of pharmaceutical technology, be specifically related to Mannitol sodium chloride injection and preparation method thereof.
Background technology
According to " standard code under two 84 pages of Mannitol sodium chloride injection items of Chinese pharmacopoeia version in 2010, when 5 hydroxymethyl furfural is measured, trap answers<0.8, at present there is the 5 hydroxymethyl furfural trap measurement result regulation that all is above standard in the listing product, and an aldehyde compound of 5 hydroxymethyl furfural to be the monosaccharide compound such as glucose dewater under the conditions such as high temperature or weak acid generation.This compound has infringement to human body striped muscle and internal organs.After the having of now listing added stabilizing agent, reach standard code, due to this product, for directly entering blood of human body, add whether stabilizing agent is harmful does not study accordingly.
Summary of the invention
The objective of the invention is to solve the problem that prior art exists, Mannitol sodium chloride injection and preparation method thereof is provided.
The present invention solves the problems of the technologies described above the technical scheme of taking to be:
Mannitol sodium chloride injection and preparation method thereof, every 1000ml consumption that is characterized in writing out a prescription, supplementary material is: glycerol 99～101g, fructose 49～51g, sodium chloride 8～10g, fresh water for injection adds to 1000ml; Concrete making step is as follows:
(1) dense join filling in access account for the water for injection of the cumulative volume 30% that makes up a prescription;
(2) ON cycle water, be cooled to 20～25 ℃;
(3) successively to the sodium chloride, glycerol, the fructose that add recipe quantity in dense preparing tank, after raw material all dissolves, open dense preparing tank liquid outlet, dilute preparing tank inlet, squeeze into dilute preparing tank;
(4) serviceability temperature is that 20～25 ℃ and the water for injection that accounts for the cumulative volume 10% that makes up a prescription rinse dense preparing tank, squeezes into dilute preparing tank, triplicate;
(5) access the water for injection that accounts for the cumulative volume 35% that makes up a prescription in dilute preparing tank, ON cycle water, stir and be cooled to 20～25 ℃;
(6) open agitating device, with rare, join ready water for injection in filling and mix homogeneously;
(7) by temperature, be that 20～25 ℃ of water for injection complements amass to 99%, pH value is surveyed in sampling, and regulates pH value between 3.8～4.2 with appropriate 0.1mol/L hydrochloric acid;
(8) complement amasss to total amount, ON cycle 15～18 minutes;
(9) from dense joining starting to finish the time used and be no more than 4 hours to rare joining;
(10) by rare distribution pipes, the inline final filter through 0.22 μ m polyether sulfone filter element is housed enters fill, described inline final filter bubble point pressure >=0.34MPa to medicinal liquid;
(11) from rare joining finishing to finish the time used to fill and be no more than 4 hours;
(12), before the product introduction sterilizing cabinet, sterilizing cabinet is warming up to 70～80 ℃;
(13) after the product introduction sterilizing cabinet, in 20～25 minutes, the sterilizing in-cabinet temperature is risen to 115 ℃, and keep 115～117 ℃ 30 minutes;
(14) after sterilizing finishes, start rapidly cooling process, in 10 minutes, the sterilizing in-cabinet temperature is down to 25～30 ℃, and the steam sterilization cabinet internal pressure is down to below 10pa simultaneously;
(15) fill is complete finishes the time used to sterilizing and is no more than 6 hours.
The present invention compared with prior art, has following beneficial effect:
By the present invention, take the product that preparing process makes to have following characteristics: this patent of invention is studied for the impurity 5 hydroxymethyl furfural problem of exceeding standard in the Mannitol sodium chloride injection of current listing.Do not add any stabilizing agent in formula, patient's medication is safer reliable.
Test report:
By above production technology, 16 batches of products of quantity-produced are followed the tracks of to investigation, all<0.6, result is as follows for the trap assay of the 5 hydroxymethyl furfural in 6 months:
| Production batch | 0 month result | March result | June result |
| 12090811 | 0.49 | 0.50 | 0.50 |
| 12090821 | 0.50 | 0.50 | 0.59 |
| 12090812 | 0.52 | 0.55 | 0.57 |
| 12090911 | 0.49 | 0.51 | 0.50 |
| 12090921 | 0.51 | 0.52 | 0.53 |
| 12090912 | 0.52 | 0.53 | 0.58 |
| 12091011 | 0.52 | 0.55 | 0.59 |
| 12091021 | 0.48 | 0.52 | 0.52 |
| 12091012 | 0.51 | 0.50 | 0.53 |
| 12091111 | 0.55 | 0.56 | 0.59 |
| 12091121 | 0.50 | 0.53 | 0.56 |
| 12091112 | 0.56 | 0.56 | 0.59 |
| 12091211 | 0.48 | 0.56 | 0.58 |
| 12091221 | 0.50 | 0.53 | 0.54 |
| 12091212 | 0.46 | 0.48 | 0.49 |
| 12091311 | 0.48 | 0.51 | 0.50 |
Annotate: the lot number preparation method is: date-serial number, and as " 12090811 " mean to be numbered on 09 08th, 2,012 11 product.
The specific embodiment
Mannitol sodium chloride injection and preparation method thereof, every 1000ml consumption that is characterized in writing out a prescription, supplementary material is: glycerol 100g, fructose 50g, sodium chloride 9g, fresh water for injection adds to 1000ml; Concrete making step is as follows:
(1) dense join filling in access account for the water for injection of the cumulative volume 30% that makes up a prescription;
(2) ON cycle water, be cooled to 20～25 ℃;
(3) successively to the sodium chloride, glycerol, the fructose that add recipe quantity in dense preparing tank, after raw material all dissolves, open dense preparing tank liquid outlet, dilute preparing tank inlet, squeeze into dilute preparing tank;
(4) serviceability temperature is that 20～25 ℃ and the water for injection that accounts for the cumulative volume 10% that makes up a prescription rinse dense preparing tank, squeezes into dilute preparing tank, triplicate;
(5) access the water for injection that accounts for the cumulative volume 35% that makes up a prescription in dilute preparing tank, ON cycle water, stir and be cooled to 22 ℃;
(6) open stirring, with rare, join ready water for injection in filling and mix homogeneously;
(7) by temperature, be that 22 ℃ of water for injection complements amass to 99%, pH value is surveyed in sampling, and regulates pH value between 3.8～4.2 with appropriate 0.1mol/L hydrochloric acid;
(8) complement amasss to total amount, ON cycle 15～18 minutes;
(9) from dense joining starting to finish the time used and be no more than 4 hours to rare joining;
(10) by rare distribution pipes, the inline final filter through 0.22 μ m polyether sulfone filter element is housed enters fill, described inline final filter bubble point pressure >=0.34MPa to medicinal liquid;
(11) from rare joining finishing to finish the time used to fill and be no more than 4 hours;
(12), before the product introduction sterilizing cabinet, sterilizing cabinet is warming up to 70～80 ℃;
(13) after the product introduction sterilizing cabinet, in 20～25 minutes, the sterilizing in-cabinet temperature is risen to 115 ℃, and keep 115～117 ℃ 30 minutes;
(14) after sterilizing finishes, start rapidly cooling process, in 10 minutes, the sterilizing in-cabinet temperature is down to 25～30 ℃, and the steam sterilization cabinet internal pressure is down to below 10pa simultaneously;
(15) fill is complete finishes the time used to sterilizing and is no more than 6 hours.
Claims (2)
1. Mannitol sodium chloride injection, it is characterized in that: every 1000ml consumption of writing out a prescription, supplementary material is: glycerol 99～101g, fructose 49～51g, sodium chloride 8～10g, fresh water for injection adds to 1000ml.
2. according to the preparation method of Mannitol sodium chloride injection claimed in claim 1, it is characterized in that: concrete making step is as follows:
(1) dense join filling in access account for the water for injection of the cumulative volume 30% that makes up a prescription;
(2) ON cycle water, be cooled to 20～25 ℃;
(3) successively to the sodium chloride, glycerol, the fructose that add recipe quantity in dense preparing tank, after raw material all dissolves, open dense preparing tank liquid outlet, dilute preparing tank inlet, squeeze into dilute preparing tank;
(4) serviceability temperature is that 20～25 ℃ and the water for injection that accounts for the cumulative volume 10% that makes up a prescription rinse dense preparing tank, squeezes into dilute preparing tank, triplicate;
(5) access the water for injection that accounts for the cumulative volume 35% that makes up a prescription in dilute preparing tank, ON cycle water, stir and be cooled to 20～25 ℃;
(6) open agitating device, with rare, join ready water for injection in filling and mix homogeneously;
(7) by temperature, be that 20～25 ℃ of water for injection complements amass to 99%, pH value is surveyed in sampling, and regulates pH value between 3.8～4.2 with appropriate 0.1mol/L hydrochloric acid;
(8) complement amasss to total amount, ON cycle 15～18 minutes;
(9) from dense joining starting to finish the time used and be no more than 4 hours to rare joining;
(10) by rare distribution pipes, the inline final filter through 0.22 μ m polyether sulfone filter element is housed enters fill, described inline final filter bubble point pressure >=0.34MPa to medicinal liquid;
(11) from rare joining finishing to finish the time used to fill and be no more than 4 hours;
(12), before the product introduction sterilizing cabinet, sterilizing cabinet is warming up to 70～80 ℃;
(13) after the product introduction sterilizing cabinet, in 20～25 minutes, the sterilizing in-cabinet temperature is risen to 115 ℃, and keep 115～117 ℃ 30 minutes;
(14) after sterilizing finishes, start rapidly cooling process, in 10 minutes, the sterilizing in-cabinet temperature is down to 25～30 ℃, and the steam sterilization cabinet internal pressure is down to below 10pa simultaneously;
(15) fill is complete finishes the time used to sterilizing and is no more than 6 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310344690.8A CN103417568B (en) | 2013-08-08 | 2013-08-08 | The preparation method of Mannitol sodium chloride injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310344690.8A CN103417568B (en) | 2013-08-08 | 2013-08-08 | The preparation method of Mannitol sodium chloride injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103417568A true CN103417568A (en) | 2013-12-04 |
| CN103417568B CN103417568B (en) | 2015-09-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310344690.8A Active CN103417568B (en) | 2013-08-08 | 2013-08-08 | The preparation method of Mannitol sodium chloride injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103417568B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104622895A (en) * | 2015-01-20 | 2015-05-20 | 石家庄四药有限公司 | Preparation method of glycerin fructose sodium chloride injection packaged in double-chamber bag |
| CN108158982A (en) * | 2017-11-16 | 2018-06-15 | 佛山双鹤药业有限责任公司 | Mannitol sodium chloride injection and production technology |
| CN114159390A (en) * | 2021-12-30 | 2022-03-11 | 辰欣药业股份有限公司 | Glycerol fructose sodium chloride injection and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102247338A (en) * | 2010-05-20 | 2011-11-23 | 西安万隆制药有限责任公司 | Composite of glycerol and fructose |
| CN102908360A (en) * | 2011-08-03 | 2013-02-06 | 四川科伦药物研究有限公司 | Glycerin fructose sodium chloride injection and preparation process thereof |
-
2013
- 2013-08-08 CN CN201310344690.8A patent/CN103417568B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102247338A (en) * | 2010-05-20 | 2011-11-23 | 西安万隆制药有限责任公司 | Composite of glycerol and fructose |
| CN102908360A (en) * | 2011-08-03 | 2013-02-06 | 四川科伦药物研究有限公司 | Glycerin fructose sodium chloride injection and preparation process thereof |
Non-Patent Citations (1)
| Title |
|---|
| 国家药典委员会: "《中华人民共和国药典2010年版二部》", 31 January 2010, 中国医药科技出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104622895A (en) * | 2015-01-20 | 2015-05-20 | 石家庄四药有限公司 | Preparation method of glycerin fructose sodium chloride injection packaged in double-chamber bag |
| CN108158982A (en) * | 2017-11-16 | 2018-06-15 | 佛山双鹤药业有限责任公司 | Mannitol sodium chloride injection and production technology |
| CN114159390A (en) * | 2021-12-30 | 2022-03-11 | 辰欣药业股份有限公司 | Glycerol fructose sodium chloride injection and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN103417568B (en) | 2015-09-09 |
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Effective date of registration: 20180118 Address after: 038300 hi tech Industrial Zone, Huairen County, Shanxi, Shuozhou Patentee after: Shanxi Nuocheng Pharmaceutical Co., Ltd. Address before: 038300 hi tech Industrial Zone, Huairen County, Shanxi, Shuozhou Patentee before: Zhang Zhiying |
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