CN102526089A - Pharmaceutical composition containing 13 kinds of vitamins - Google Patents
Pharmaceutical composition containing 13 kinds of vitamins Download PDFInfo
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- CN102526089A CN102526089A CN2011104485703A CN201110448570A CN102526089A CN 102526089 A CN102526089 A CN 102526089A CN 2011104485703 A CN2011104485703 A CN 2011104485703A CN 201110448570 A CN201110448570 A CN 201110448570A CN 102526089 A CN102526089 A CN 102526089A
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Abstract
The invention discloses a pharmaceutical composition containing 13 kinds of vitamins, which is characterized in that the pharmaceutical composition is an injection preparation formed by vitamin A palmitate, tetrahydrate cocarboxylase, lactoflavin sodium phosphate, vitamin B12, vitamin D3, vitamin K1, vitamin B6, vitamin C, niacinamide, folacin, racemic alpha-tocopheryl, biotin, dexpanthenol, soybean phospholipid, glycocholic acid, citric acid, cysteine hydrochloride and excipients. According to the pharmaceutical composition, the deficiencies in the prior art are overcome; and indicated by experimental results, the formed injection preparation has the advantages of long-term stability in quality and more safety in clinical use.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, be specifically related to a kind of pharmaceutical composition that contains 13 kinds of vitamin and preparation method thereof.
Background technology
13 kinds of composite vitamin injections are the parenteral alimentation intravenous formulations; These article are for containing the Cernevit-12 of water soluble vitamins and fatsoluble vitamin; Can supply the adult and child's vitimin supplement more than 11 years old; Be applicable to through enteral nutritional support picked-up not enough (like malnutrition or gastrointestinal absorption obstacle etc.), or through gastrointestinal nutrition taboo person.The serious nutritional status that can be used for recurring changes the situation of metabolic emergency reaction of lower body and histotrophic nutrition shortage.These article can provide the intake of essential vitamin to keep body normal reaction and reparation.
Prior art mainly concentrates on the research of 13 kinds of composite vitamin injections its each component is realized dissolving each other the aspect; Promptly mainly increase the dissolving of liposoluble constituent through studying different solubilizing agents and cosolvent; Realize dissolving mutually, produce the injection that contains whole 13 kinds of components with water soluble vitamins; Also have water soluble vitamins and fatsoluble vitamin are separated the way of adorning, when clinical use, prepare temporarily, not only operation inconvenience but also microbiological contamination easily.Because various vitamin ingredients are particularly responsive to the metal ion catalysis effect to light, heat, pH sensitivity, therefore in the preparation process, will overcome the effect of metal ion; Because of vitamin is the necessary material of bacterial growth, bacterial reproduction very easily, unsuitable again high temperature sterilize is so have strict requirement, the use otherwise product will can't dispatch from the factory because of sterility test is defective to production.Most of component is easy to oxidizedly in 13 kinds of Cernevit-12s in addition, and like racemization alpha-tocopherol (vitamin E), vitamin C etc., after long-time the placement, racemization alpha-tocopherol, ascorbic content significantly descend.For overcoming above-mentioned defective; Available technology adopting chelating agen, antioxidant, antiseptic solve and are prone to oxidation and easy microbiological contamination problem; Like disodium edetate, sodium sulfite, sodium pyrosulfite, Butylated hydroxyanisole, two uncle butylparaben cresol, sodium benzoate, sodium methyl phydroxybenzoate class etc. what yet these compositions had can only be used on the water soluble ingredient, and what have can only singly be used in the fat-soluble composition; And these composition toxicity are bigger; Human body there is bigger toxic and side effects; Particularly these compositions directly get into blood through intravenous injection; Harm to human body is just bigger; Therefore strict restriction has all been made to its consumption by each traditional Chinese medicines prison department, have in addition forbid on medicine, using as additives. therefore the needs searching harmless and can be simultaneously water solublity and liposoluble constituent be played the antioxidant and the antiseptic of antioxygen and antisepsis, contain the quality and the safety of 13 kinds of compound vitamin ejection preparations with raising; This is the difficult problem that must solve of 13 kinds of stable compound vitamin ejection preparations of the present quality of production, but is not resolved up to now.
Summary of the invention
Above-mentioned defective to prior art; The invention provides a kind of pharmaceutical composition that contains 13 kinds of vitamin; Do not contain harmful antioxidant and antiseptic composition in the said composition; Simultaneously water solublity and liposoluble constituent are had antioxygen and antisepsis, thereby make product quality also more stable, clinical practice is safer.
The purpose of this invention is to provide a kind of pharmaceutical composition that contains 13 kinds of vitamin; Said composition adopts a kind of antioxidant that does not contain harmful ingredients and antiseptic; Simultaneously can all have antioxygen and antisepsis to water solublity and liposoluble constituent; Can make the active component content in the preparation more stable, described ejection preparation comprises injection and lyophilized injectable powder.
Another object of the present invention provides a kind of preparation of drug combination method that contains 13 kinds of vitamin.
The objective of the invention is to realize through following technical scheme.
A kind of pharmaceutical composition that contains 13 kinds of vitamin is characterized in that it being the ejection preparation of being processed by the active component and the adjuvant of following component:
PH5.0-7.0 processes 1000 bottles;
Said ejection preparation is a kind of in lyophilized injectable powder, the injection, does not add excipient during the preparation injection;
Said excipient is a kind of in glycine and the mannitol.
A kind of pharmaceutical composition that contains 13 kinds of vitamin is the ejection preparation of being processed by the active component and the adjuvant of following component:
PH6.0 processes 1000 bottles of lyophilized injectable powders, does not add glycine during the preparation injection.
A kind of preparation of drug combination method that contains 13 kinds of vitamin is characterized by and may further comprise the steps:
(1) injection preparation
A. heat in the water for injection water-bath, subsequent use after citric acid, the cysteine hydrochloride adding dissolving;
B. get soybean phospholipid, glycocholic acid contains citric acid, the dissolving of CYSTEAMINE HCL acid solution in right amount filling under the nitrogen environment adding, adds vitamin A palmitate, vitamin D again
3, racemization alpha-tocopherol, vitamin K1, mix making dissolving, fatsoluble vitamin solution, subsequent use:
C. prepare sodium hydroxide solution, get folic acid, biotin, add an amount of sodium hydroxide solution dissolving, subsequent use;
D. filling under the nitrogen environment all the other vitamin with the solution dissolving that contains citric acid, cysteine hydrochloride, merge with above-mentioned reserve liquid, adjustings pH is 5.0-7.0, the adding active carbon; Stir, filter, add to the full amount of water for injection fine straining; Aseptic filtration, fill, every 5ml seals promptly and gets;
(2) lyophilized injectable powder preparation
A. heat in the water for injection water-bath, subsequent use after citric acid, the cysteine hydrochloride adding dissolving;
B. get soybean phospholipid, glycocholic acid contains citric acid, the dissolving of CYSTEAMINE HCL acid solution in right amount filling under the nitrogen environment adding, adds vitamin A palmitate, vitamin D again
3, racemization alpha-tocopherol, vitamin K1, mix making dissolving, fatsoluble vitamin solution, subsequent use:
C. prepare sodium hydroxide solution, get folic acid, biotin, add an amount of sodium hydroxide solution dissolving, subsequent use;
D. filling under the nitrogen environment with solution all the other vitamin of dissolving and the excipient that contain citric acid, cysteine hydrochloride, merge with above-mentioned reserve liquid, adjusting pH is 5.0-7.0; Add active carbon, stir coarse filtration; Add to the full amount of water for injection fine straining, aseptic filtration; Be sub-packed in the cillin bottle, every bottle of 2.5ml promptly gets with conventional freeze drying process lyophilizing.
Though the applicant finds prior art under study for action and adopts conventional antioxidant for the preparation stability in the large raising to be arranged; But after the long-time placement of preparation, particularly stable poor racemization alpha-tocopherol (vitamin E) and Vitamin C content are placed in time and are descended obviously; Because the most component of these article is to thermo-responsive; So can not adopt high temperature sterilize in producing: fatsoluble vitamin is worked and prior art adopts that the antioxidant of routine has; What have only works to water soluble vitamins, is difficult to be applicable to the preparation that contains fatsoluble vitamin and water soluble vitamins composition simultaneously; Used antioxidant all has certain toxicity to body in the prior art simultaneously; And used antiseptic has toxicity to body equally in the prior art; These two kinds of adjuvant be must to use again but prepare 13 kinds of vitamin preparations, otherwise the steady quality and the security of products of preparation just can't be guaranteed.
The applicant finds when using the combination of citric acid and cysteine hydrochloride through big quantity research, each component long-term storage of preparation, and not oxidized, active component content stability has unforeseeable raising, has the antiseptic effect again simultaneously, and product microbiological contamination rate is 0; Can play antioxygen and antisepsis simultaneously to water solublity and fatsoluble vitamin composition, this is our unexpected discovery; Most preferably citric acid is 5.0g, and cysteine hydrochloride is 1.5g.
Further discovering, is 5.0g at optimization citric acid, and cysteine hydrochloride is under the 1.5g condition, and the particulate matter of preparation is more stable, and this is again our unexpected discovery; Because above-mentioned preparation uses in the intravenous injection of being everlasting, thisly make the more stable effect of particulate matter in the preparation for guaranteeing the clinical safe in utilization significant of preparation.
The antioxidant experimental result
Be the influence of more different antioxidant to the preparation antioxidant effect, we contain the medicine composition injection of 13 kinds of vitamin by the preparation of following prescription, and are that the basis compares antioxidant with the injection.
Water for injection adds to 5000ml, and pH6.0 processes 1000 of injection;
Use therein different contrast antioxidant experiment group is respectively:
Comparative formulation 1: in above-mentioned preparation prescription, remove citric acid, cysteine hydrochloride adds sodium sulfite 10g;
Comparative formulation 2: in above-mentioned preparation prescription, remove citric acid, cysteine hydrochloride adds sodium pyrosulfite 10g;
Comparative formulation 3: in above-mentioned preparation prescription, remove citric acid, cysteine hydrochloride adds disodium edetate 10g;
Comparative formulation 4: in above-mentioned preparation prescription, remove cysteine hydrochloride, an adding citric acid 5g;
Comparative formulation 5: in above-mentioned preparation prescription, remove citric acid, only add cysteine hydrochloride to 10g;
The application's experimental group antioxidant combination is respectively:
Experimental group 1: in above-mentioned preparation prescription, the adjustment citric acid is 1g, and cysteine hydrochloride is 1g;
Experimental group 2: in above-mentioned preparation prescription, the adjustment citric acid is 10g, and cysteine hydrochloride is 5g;
Experimental group 3: in above-mentioned preparation prescription, the adjustment citric acid is 10g, and cysteine hydrochloride is 1g;
Experimental group 4: in above-mentioned preparation prescription, the adjustment citric acid is that 1g and cysteine hydrochloride are 5g;
Experimental group 5: in above-mentioned preparation prescription, promptly citric acid is 5g and cysteine hydrochloride 1.5g.
Because vitamin E (racemization alpha-tocopherol) and vitamin C (ascorbic acid) are least stable compositions wherein, investigate the effect of each antioxidant in therefore testing with vitamin E and ascorbic changes of contents.
Because preparation is placed (2 years) for a long time; Time is longer big more to content influence; Be better comparison, the applicant is 25 ± 2 ℃ with each 100 in the preparation of said components in temperature, and relative humidity is 60% ± 10% condition held 24 months; And be 100% to calculate the racemization alpha-tocopherol and the ascorbic content of test after 24 months with 0 month content, the result sees table 1.
Table 1 is racemization alpha-tocopherol content results after 24 months
| Group | Racemization alpha-tocopherol content (%) | Vitamin C content (%) |
| Comparative formulation 1 | ?93.5 | ?90.3 |
| Comparative formulation 2 | ?94.5 | ?90.5 |
| Comparative formulation 3 | ?92.7 | ?91.2 |
| Comparative formulation 4 | ?84.1 | ?92.1 |
| Comparative formulation 5 | ?62.0 | ?59.6 |
| Experimental group 1 | ?97.4＊ | ?95.2＊ |
| Experimental group 2 | ?98.9＊ | ?97.2＊ |
| Experimental group 3 | ?97.8＊ | ?97.6＊ |
| Experimental group 4 | ?97.5＊ | ?95.8＊ |
| Experimental group 5 | ?99.1＊＊ | ?98.7＊＊ |
Annotate: compare * P＜0.05 with the Comparative formulation group; * P＜0.01.
This shows; From racemization alpha-tocopherol and Vitamin C content decline situation; The application's antioxidant combination has the effect that more significantly improves preparation stability, and the combined effect that other antioxidants are asked in all not having originally is remarkable, and citric acid and cysteine hydrochloride are when using separately; Very low antioxidation is only arranged, explain that antioxidant citric acid of this experimental group and cysteine hydrochloride combination have collaborative antioxidation; Simultaneously because citric acid and cysteine hydrochloride are water-soluble substanceses; And the racemization alpha-tocopherol is a liposoluble substance; Experiment proof antioxidant citric acid and cysteine hydrochloride combination not only have antioxidation to water soluble ingredient; And liposoluble substance also possessed antioxidation, produced the technique effect that those skilled in the art can't reckon with. wherein consider the consumption factor best be the combination of the application's experimental group 5.And further experiment shows, when using the conventional cosolvent of prior art, above-mentioned comparative result is not had appreciable impact.
According to above-mentioned result of the test, we adopt identical prescription, add excipient; Be prepared into freeze-dried powder, place 24 months by above-mentioned similarity condition after, be dissolved into injection with 5ml water for injection for every bottle; Measure racemization alpha-tocopherol and Vitamin C content, the result sees table 2.
Table 2 freeze-dried powder is placed racemization alpha-tocopherol and Vitamin C content result after 24 months
Annotate: compare * P＜0.05 with the Comparative formulation group;
Table 2 is the result show, antioxidant combination of the present invention has the effect that more significantly improves preparation stability, is superior to the antioxidant of prior art.
Comparison sheet 1 and table 2 result can also find that the stability of lyophilized injectable powder is superior to injection; Although the comparative example measured value is lower than the experimental group measured value in the table 2, require from pharmaceutical formulations, except that Comparative Examples 5, all the other Comparative Examples all meet the requirements.
The comparative experiments of bacteriostasis
For carry out this experiment, prepare the injection that contains 13 kinds of vitamin combinations by conventional method, the basic prescription as follows:
Water for injection adds to 5000ml, and pH6.0 processes 1000.
Or add excipient glycine 250g, water for injection adds to 2500ml, processes 1000 bottles of lyophilized injectable powders.
Sample 1 is the injection of basic prescription preparation;
Sample 2 adds disodium edetate 1000mg, nipabutyl sodium 1000mg, the injection of preparation for basic prescription removes citric acid and cysteine hydrochloride.
Sample 3 adds the injection of disodium edetate 1000mg preparation for basic prescription removes citric acid and cysteine hydrochloride.
Sample 4 prepares lyophilized injectable powder for sample 1 adds excipient by method for preparing freeze-dried powder;
Sample 5 prepares lyophilized injectable powder for sample 2 adds excipient by method for preparing freeze-dried powder;
Sample 6 prepares lyophilized injectable powder for sample 3 adds excipient by method for preparing freeze-dried powder.
Because the ejection preparation of compound vitamin can not adopt the terminal autoclave sterilization; Because of vitamin is the necessary material of bacterial growth; Very easily bacterial growth breeding; So must add some necessary antiseptic such as sodium benzoate or sodium methyl phydroxybenzoate during conventional preparation said preparation waits and suppresses microbiological contamination; Otherwise just can't guarantee the drug quality safety of preparation in the shelf-life. so we get three kinds of sample injection liquid and three kinds of sample lyophilized injectable powders each 100 bottles long-time (15 months) are placed, and get 5 bottles of per sample (p.s.)s, and do aseptic detection by 2005 editions two appendix XIH sterility tests of Chinese Pharmacopoeia method in every month; Find that sample has detected bacterium in cultivating, and promptly is judged to be microbiological contamination. result of the test is seen table 3.
The aseptic testing result of the long-time placement of six kinds of samples of table 3
Explain: microbiological contamination is not found in-expression; Microbiological contamination is found in+expression.
Sample 3 preparations are just found microbiological contamination in February, and the 3rd, in detecting April microbiological contamination are arranged all, inspection after therefore just no longer listing in from 5th month.
Sample 6 preparations are found microbiological contamination in November, and in detecting in the 12nd, 13 month, microbiological contamination are arranged all, inspection after therefore just no longer listing in from 14th month.
Result of the test shows, the very easily microbiological contamination of compound vitamin ejection preparation needs to add antibacterial; Sample 1 though 4 do not add conventional antibacterial, has good antibacterial effect; And sample 3 and 6 is found microbiological contamination respectively, shows to use conventional antioxidant, and adding preservative agent is not dangerous; It can also be seen that from the result that in addition lyophilized formulations is more stable than injection; Further research shows that this effect possibly be citric acid and the synergistic result of cysteine hydrochloride.
Further experiment to cosolvent
In order further to compare and to seek the most stable combination of preparation particulate matter, the applicant has carried out further research.
For carry out this experiment, prepare the injection that contains 13 kinds of vitamin-medicine compositions by conventional method, the basic prescription as follows:
Water for injection adds to 5000ml, and pH6.0 processes 1000 bottles of injection;
Comparative Examples 1 is removed citric acid and cysteine hydrochloride in the above-mentioned prescription, adds disodium edetate 1000mg, nipabutyl sodium 1000mg.
Comparative Examples 2 prescriptions are identical with Comparative Examples 1, but with lecithin 112.5g+ sodium cholate 112.5g, replace the cosolvent combination of soybean phospholipid and glycocholic acid;
Comparative Examples 3 prescriptions are identical with Comparative Examples 1, but cosolvent is lecithin 112.5g+ glycocholic acid 90g, replace the cosolvent combination of soybean phospholipid and glycocholic acid;
Comparative Examples 4 prescriptions are identical with Comparative Examples 1, but cosolvent is glycerol 120g+ sodium cholate 112.5g, replace the cosolvent combination of soybean phospholipid and glycocholic acid;
Experimental example 1 is the embodiment of the invention 1 combination;
Experimental example 2 is the embodiment of the invention 5 combinations;
Experimental example 3 is the embodiment of the invention 6 combinations.
The particulate matter experimental result
Get the experimental example sample in the present invention research and comparative example has been carried out Journal of Sex Research steady in a long-term.
The investigation condition: with reference to Chinese Pharmacopoeia version appendix in 2005 medicine stability test guideline, be 25 ± 2 ℃ in temperature, relative humidity 60% scholar 10% condition held 24 months.
Investigation project: character, pH, clarity, particulate matter, assay.
Experimental result shows that character, clarity, the pH of experimental example preparation and Comparative Examples preparation in the put procedure change all not obvious; Meet the correlated quality requirement of ejection preparation; And 24 months content results also shows experimental example and comparative example product content all meet the requirements (was 100% as reference with 0 month testing result); But the particulate matter of measuring by 2005 editions two appendix IXC particulate matters of pharmacopeia inspection technique changes obviously in time; Particulate matter that its mensuration obtains and assay result see table 4, table 5, table 6.
24 months assay results (%) of table 4
Table 5 long-time stability experiment particulate matter is measured result's (number/milliliter more than 10 microns)
Table 6 long-time stability experiment particulate matter is measured result's (number/milliliter more than 25 microns)
Above-mentioned experimental result shows that the formulation components that adopts antioxidant of the present invention is relatively stable at 24 months content; Particulate matter all can change in time in the Comparative Examples injection but experimental result is illustrated in; Particularly change greatly through long-time its particulate matter of back of placing, this variation has reflected the existence of insecurity factor in the preparation system, and the antioxidant that the application adopts helps the hydrotropy composition keeping the stable of preparation active constituent content; Keep the stable of particulate matter in the injection simultaneously; This is that we find unexpectedly, and does not find relevant this respect report in the prior art, and this more helps clinical safety and use undoubtedly.
Below through embodiment technical scheme of the present invention is described further:
Embodiment 1:
Water for injection adds to 5000ml, processes 1000 of injection;
Method for preparing:
A. heat in the water for injection water-bath, antioxidant adding dissolving back is subsequent use;
B. get soybean phospholipid, glycocholic acid contains citric acid, the dissolving of CYSTEAMINE HCL acid solution in right amount filling under the nitrogen environment adding, adds vitamin A palmitate, vitamin D again
3, racemization alpha-tocopherol, vitamin K1, mix making dissolving, fatsoluble vitamin solution, subsequent use:
C. prepare sodium hydroxide solution, get folic acid, biotin, add an amount of sodium hydroxide solution dissolving, subsequent use;
D. filling under the nitrogen environment all the other vitamin with containing citric acid, the dissolving of CYSTEAMINE HCL acid solution, merge with above-mentioned reserve liquid, regulating pH is 5.9, adds active carbon; Stir, filter, add to the full amount of water for injection fine straining; Fill, aseptic filtration, every 5ml seals promptly and gets.
Embodiment 2
Water for injection adds to 2500ml, processes 1000 bottles of lyophilized injectable powders;
The lyophilized injectable powder method for preparing
A. heat in the water for injection water-bath, subsequent use after citric acid, the cysteine hydrochloride adding dissolving;
B. get soybean phospholipid, glycocholic acid contains citric acid, the dissolving of CYSTEAMINE HCL acid solution in right amount filling under the nitrogen environment adding, adds vitamin A palmitate, vitamin D again
3, racemization alpha-tocopherol, vitamin K1, mix making dissolving, fatsoluble vitamin solution, subsequent use:
C. prepare sodium hydroxide solution, get folic acid, biotin, add an amount of sodium hydroxide solution dissolving, subsequent use;
D. filling under the nitrogen environment with solution all the other vitamin of dissolving and the freeze drying protectant that contain citric acid, cysteine hydrochloride, merge with above-mentioned reserve liquid, regulating pH is 6.0, adds active carbon; Stir coarse filtration, fine straining, aseptic filtration; Be sub-packed in the cillin bottle, every bottled amount 2.5ml, conventional lyophilizing promptly gets.
Embodiment 3
Water for injection adds to 2500ml, and pH6.2 processes 1000 bottles of lyophilized injectable powders;
Method for preparing is with embodiment 2, and adjusting pH is 6.2.
Embodiment 4
Water for injection adds to 2500ml, and pH5.5 processes 1000 bottles of lyophilized injectable powders;
Method for preparing is with embodiment 2, and adjusting pH is 5.5.
Embodiment 5
Process 1000 of injection;
Method for preparing is with embodiment 1, and adjusting pH is 5.8.
Embodiment 6
Process 1000 of injection;
Method for preparing is with embodiment 1, and adjusting pH is 6.5.
Claims (3)
1. pharmaceutical composition that contains 13 kinds of vitamin is characterized in that it being the ejection preparation of being processed by the active component and the adjuvant of following component:
PH5.0-7.0 processes 1000 bottles;
Said ejection preparation is a kind of in lyophilized injectable powder, the injection, does not add excipient during the preparation injection;
Said excipient is a kind of in glycine and the mannitol.
2. according to a kind of pharmaceutical composition that contains 13 kinds of vitamin of claim 1, be the ejection preparation of processing by the active component and the adjuvant of following component:
PH6.0 processes 1000 bottles of lyophilized injectable powders, does not add glycine during the preparation injection.
3. according to each a kind of preparation of drug combination method that contains 13 kinds of vitamin of claim 1-2, it is characterized by and may further comprise the steps:
(1) injection preparation
A. heat in the water for injection water-bath, subsequent use after citric acid, the cysteine hydrochloride adding dissolving;
B. get soybean phospholipid, glycocholic acid contains citric acid, the dissolving of CYSTEAMINE HCL acid solution in right amount filling under the nitrogen environment adding, adds vitamin A palmitate, vitamin D again
3, racemization alpha-tocopherol, vitamin K1, mix making dissolving, fatsoluble vitamin solution, subsequent use:
C. prepare sodium hydroxide solution, get folic acid, biotin, add an amount of sodium hydroxide solution dissolving, subsequent use;
D. filling under the nitrogen environment all the other vitamin with the solution dissolving that contains citric acid, cysteine hydrochloride, merge with above-mentioned reserve liquid, adjustings pH is 5.0-7.0, the adding active carbon; Stir, filter, add to the full amount of water for injection fine straining; Aseptic filtration, fill, every 5ml seals promptly and gets;
(2) lyophilized injectable powder preparation
A. heat in the water for injection water-bath, subsequent use after citric acid, the cysteine hydrochloride adding dissolving;
B. get soybean phospholipid, glycocholic acid contains citric acid, the dissolving of CYSTEAMINE HCL acid solution in right amount filling under the nitrogen environment adding, adds vitamin A palmitate, vitamin D again
3, racemization alpha-tocopherol, vitamin K1, mix making dissolving, fatsoluble vitamin solution, subsequent use:
C. prepare sodium hydroxide solution, get folic acid, biotin, add an amount of sodium hydroxide solution dissolving, subsequent use;
D. filling under the nitrogen environment with solution all the other vitamin of dissolving and the excipient that contain citric acid, cysteine hydrochloride, merge with above-mentioned reserve liquid, adjusting pH is 5.0-7.0; Add active carbon, stir coarse filtration; Add to the full amount of water for injection fine straining, aseptic filtration; Be sub-packed in the cillin bottle, every bottle of 2.5ml promptly gets with conventional freeze drying process lyophilizing.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109620832A (en) * | 2019-01-14 | 2019-04-16 | 大连大学 | Glycocholic acid is preparing the application in resisting hyperplasia of mammary glands drug |
| CN111329839A (en) * | 2020-04-02 | 2020-06-26 | 北京鑫兰医药科技有限公司 | Composite vitamin freeze-dried preparation and preparation method thereof |
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| CN101433547A (en) * | 2008-12-19 | 2009-05-20 | 江苏万邦生化医药股份有限公司 | Method for preparing twelve kinds of composite vitamins for injection |
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Patent Citations (5)
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|---|---|---|---|---|
| JP2005179200A (en) * | 2003-12-16 | 2005-07-07 | Terumo Corp | Vitamin b1 containing infusion |
| US20060286172A1 (en) * | 2005-06-03 | 2006-12-21 | Anu Mahashabde | Pharmaceutical compositions comprising prostanoid-receptor agonists and methods of making and using the same |
| CN1843327A (en) * | 2006-04-17 | 2006-10-11 | 重庆医药工业研究院有限责任公司 | Stable freeze-dried formulation containing multiple kinds of vitamin and its preparation method |
| CN101357118A (en) * | 2008-09-26 | 2009-02-04 | 郑飞雄 | Medicine composition containing 15 kinds of amino acid and preparation method thereof |
| CN101433547A (en) * | 2008-12-19 | 2009-05-20 | 江苏万邦生化医药股份有限公司 | Method for preparing twelve kinds of composite vitamins for injection |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109620832A (en) * | 2019-01-14 | 2019-04-16 | 大连大学 | Glycocholic acid is preparing the application in resisting hyperplasia of mammary glands drug |
| CN109620832B (en) * | 2019-01-14 | 2021-01-01 | 大连大学 | Application of glycocholic acid in preparation of anti-hyperplasia of mammary glands medicine |
| CN111329839A (en) * | 2020-04-02 | 2020-06-26 | 北京鑫兰医药科技有限公司 | Composite vitamin freeze-dried preparation and preparation method thereof |
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| CN102526089B (en) | 2014-02-05 |
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