CN102652744B - Modified injection containing 13 compound vitamins and preparation method thereof - Google Patents
Modified injection containing 13 compound vitamins and preparation method thereof Download PDFInfo
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- CN102652744B CN102652744B CN201110048015.1A CN201110048015A CN102652744B CN 102652744 B CN102652744 B CN 102652744B CN 201110048015 A CN201110048015 A CN 201110048015A CN 102652744 B CN102652744 B CN 102652744B
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Abstract
The invention discloses a modified injection pharmaceutical composition containing 13 compound vitamins and a preparation method thereof, and relates to the field of medicinal preparations. In order to solve the problems of poor stability and rigorous preservation conditions of similar injections in the prior art, the invention discloses a compound vitamin injection pharmaceutical composition which is separatedly loaded in two ampoules, and comprises 4 fat-soluble vitamins and 9 water-soluble vitamins in total; meanwhile solubilizers, antioxidants and preparation technology of the compound vitamin injection pharmaceutical composition are also modified. The compound vitamin injection pharmaceutical composition prepared by the invention has significantly improved stability, and can be preserved for 18 months at room temperature.
Description
Technical field
The invention belongs to technical field of medicine, particularly a kind of improved Compsoite vitamin injection pharmaceutical composition and preparation method thereof.
Background technology
Vitamin (vitamin) is that humans and animals is to maintain normal physiological function and the class trace organic substance that must obtain from food, in people's bulk-growth, metabolism, growth course, play an important role, being to maintain the necessary type organic matter of human life activity, is also the important active substances that keeps health.Vitamin content is in vivo little, but indispensable.Although the chemical constitution of various vitamin and character are different, they have following common ground: the first, vitamin is prevalent in food; The second, the effect of vitamin is mainly the adjusting that participates in organism metabolism; Three, most vitamin, body can not synthesize or synthetic quantity deficiency, can not meet the needs of body, must often obtain by the external world; Four, human body is very little to the requirement of vitamin, once but shortage will cause corresponding avitaminosis, health caused damage.
Vitamin can be divided into fatsoluble vitamin and water soluble vitamins according to the dissolubility of vitamin.Fatsoluble vitamin comprises vitamin A, vitamin D, vitamin E, vitamin K
1four kinds, in food, jointly exist with lipid, in the time of intestinal absorption, also absorb relevantly with lipid, excretion efficiency is low, therefore take in when too much, can accumulate in vivo, produces illeffects, even occurs poisoning.Water soluble vitamins comprises vitamin B complex, vitamin C (ascorbic acid) and choline.Wherein, vitamin B complex comprises vitamin B
1(thiamine hydrochloride), vitamin B
2(riboflavin), vitamin B
6(Pyridoxine Hydrochloride), vitamin B
12, nicotinic acid, pantothenic acid, folic acid, biotin.Nicotiamide is water soluble vitamins, nadide and coenzyme II ingredient, become the coenzyme of many dehydrogenases, when shortage, can affect the eupnea of cell and metabolism and cause pellagra, easily absorb, after absorption, be distributed to body tissue, through liver metabolism, only discharge from urine with original shape on a small quantity, for supplementing the nutrients and treating glossitis, dermatitis etc.Dexpanthenol is vitamin(e) B group medicine, participates in metabolism; There is the metabolism that promotes human body protein, fat, saccharide, promote skin and mucomembranous cell growth, improve hair luster, improve immunity, the effects such as antiinflammatory.
Due to the particularity of vitamin character, the vitamins preparation of current domestic listing exists mainly with folk prescription form, and not yet has at present listing product with the small-volume injection of water solublity and fatsoluble vitamin composition.13 kinds of Compsoite vitamin injection pharmaceutical compositions of external listing are the INFUVITADULT (Multiple Vitaminsfor Infusion) of hundred spies (Baxter) company.This product is two ampoule packagings.In No. 1 ampoule of INFUVITADULT, contain vitamin C, vitamin A palmitate, vitamin D
3, vitamin B
1, vitamin B
2, Pyridoxine Hydrochloride, nicotiamide, Dexpanthenol, vitamin E, vitamin K, in No. 2 ampoules, contain folic acid, biotin, vitamin B
12; In No. 1 ampoule, contain 1.4% Tween 80 (having another name called polyoxyethylene sorbitan monoleate), as solubilizing agent.This product adopts flowing steam sterilization (100 DEG C, 30min), and finished product is in 2-8 DEG C of preservation.Chinese patent application CN101073580A discloses a kind of 13 kinds of Compsoite vitamin injection pharmaceutical compositions, the effective ingredient of its Compsoite vitamin injection pharmaceutical composition the first bottle is identical with INFUVIT ADULT1 ampoule, but its adjuvant contains solubilizing agent Tween 80 and propylene glycol simultaneously, antioxidant sodium sulfite and complexing of metal ion agent calcio-disodium edetate.Equally, the Compsoite vitamin injection pharmaceutical composition that the technical scheme that CN101073580A records makes also adopts flowing steam sterilization (100 DEG C, 30min).Sterilising conditions depends on the stability of injection, and injection is more stable, and its sterilising conditions that can tolerate is higher, otherwise, lower.
Summary of the invention
Not high for 13 kinds of Compsoite vitamin injection pharmaceutical composition stability that exist in above-mentioned prior art, the problems such as preservation condition harshness, the invention provides a kind of improved 13 kinds of Compsoite vitamin injection pharmaceutical compositions and preparation method thereof.
In order to realize foregoing invention object, the technical solution used in the present invention is as follows:
A kind of improved 13 kinds of Compsoite vitamin injection pharmaceutical compositions, are divided in two ampoules, and the first ampoule injection contains: vitamin A palmitate, vitamin K
1, vitamin D
3, vitamin E, vitamin C, vitamin B
1, riboflavin sodium phosphate, Dexpanthenol, vitamin B
6, nicotiamide and pH adjusting agent; The second ampoule injection contains: vitamin B
12, folic acid, biotin, stabilizing agent and pH adjusting agent; It is characterized in that, in the first ampoule injection, contain Tween 80, and any of propylene glycol or ethanol.
By the adjuvant to the first ampoule, the especially selection of solubilizing agent, even if do not add antioxidant, the stability of the first ampoule is also significantly increased compared with prior art.
Certainly,, in order further to improve the stability of the first ampoule injection, the present invention's the first ampoule injection can further contain any or theys' of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) or Radix Gentianae acyl ethanolamine any mixture.Wherein BHA, BHT are fat-soluble antioxidant, and Radix Gentianae acyl ethanolamine is water solublity antioxidant.
Described butylated hydroxyanisole consumption can be 0～0.005mg/ml, and described butylated hydroxytoluene consumption can be 0～0.02mg/ml, and described Radix Gentianae acyl ethanolamine consumption can be 0～0.04g/ml.
As preferably, in the first ampoule injection of 13 kinds of Compsoite vitamin injection pharmaceutical compositions of the present invention, the consumption of Tween 80 is 12～20mg/ml, and the consumption of propylene glycol is that the consumption of 0.001～0.3g/ml or ethanol is 0.001～0.3ml/ml.
As the stabilizing agent of the second ampoule injection, as long as pharmaceutically suitable stabilizing agent all can, the preferred propylene glycol of the present invention, wherein the consumption of propylene glycol is 0.001～0.3g/ml.
As further preferably, the invention provides a kind of improved 13 kinds of Compsoite vitamin injection pharmaceutical compositions, it is characterized in that, described the first ampoule injection consists of the following composition: vitamin A palmitate 3300IU, vitamin K
10.15mg, vitamin D
3200IU, vitamin e1 0IU, Catergen 00mg, vitamin B
16mg, riboflavin sodium phosphate 5mg(are in riboflavin 3.6mg), Dexpanthenol 15mg, vitamin B
66mg, nicotiamide 40mg, Tween 80 (consumption is 12～20mg/ml) and propylene glycol (consumption is 0.001～0.3g/ml) or ethanol (consumption is 0.001～0.3ml/ml), pH adjusting agent regulates pH value to 4～7; Described the second ampoule injection consists of the following composition: vitamin B
125 μ g, folic acid 6mg, biotin 60 μ g, propylene glycol (consumption is 0.001～0.3g/ml), pH adjusting agent regulates pH value to 4.5～7.
As the pH adjusting agent of the first ampoule injection, as long as pharmaceutically suitable pH adjusting agent all can, the preferred sodium hydroxide of the present invention.As the pH adjusting agent of the second ampoule injection, as long as pharmaceutically suitable pH adjusting agent all can, any of preferably citric acid of the present invention or sodium citrate or their any mixture.
In the present invention, the consumption described in each adjuvant, refers to the content of corresponding adjuvant in corresponding injection.
The preparation method of aforementioned 13 kinds of Compsoite vitamin injection pharmaceutical compositions, comprises the steps:
(1) first ampoule: measure vitamin A palmitate, vitamin K by prescription
1, vitamin D
3, vitamin E is placed in container, mix homogeneously, adds recipe quantity Tween 80 to continue to be mixed to evenly, obtains oil-phase solution, takes vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6be placed in container, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 3～5 by pH adjusting agent, add recipe quantity propylene glycol or ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filter, oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, pH adjusting agent regulates pH to 4～7, benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, sterilizing;
(2) second ampoules: take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature, stirring and dissolving under nitrogen protection; Add recipe quantity stabilizing agent to stir miscible, pH adjusting agent is adjusted pH to 4.5～7, adds dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that is cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, sterilizing.
In the time containing above-mentioned antioxidant in the first ampoule, the preparation method of aforementioned 13 kinds of Compsoite vitamin injection pharmaceutical compositions of the present invention, comprises the steps:
(1) first ampoule: measure vitamin A palmitate, vitamin K by prescription
1, vitamin D
3, vitamin E and butylated hydroxyanisole and/or butylated hydroxytoluene be placed in container, heating-up temperature, to stirring, then adds Tween 80 to continue to be stirred to evenly, obtains oil-phase solution, takes vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine is placed in container, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 3～5 by pH adjusting agent, add recipe quantity propylene glycol or ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filter, oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, with pH adjusting agent adjusting pH to 4～7, benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, sterilizing;
(2) second ampoules: take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature, stirring and dissolving under nitrogen protection; Add recipe quantity stabilizing agent to stir miscible, pH adjusting agent is adjusted pH to 4.5～7, adds dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that is cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, sterilizing.
In aforementioned preparation method, the preferred sodium hydroxide of the first ampoule pH adjusting agent, any of the second ampoule pH adjusting agent preferably citric acid or sodium citrate or their any mixture.Step (one), the step (two) of aforementioned preparation method are all two independent processes, there is no operational order between them.
Now be further described with regard to technical scheme of the present invention.
The screening of solubilizing agent in (one) first ampoule
In order to reach identical or better solubilizing effect, inventor finds after deliberation, Tween 80 and propylene glycol, or Tween 80 and ethanol are jointly as solubilizing agent, can improve solubilizing effect.Inventor investigates the content of Tween 80, in the time that the consumption of Tween 80 is less than 12mg/ml, muddiness easily occurs after injection sterilizing, and Tween 80 is comparatively suitable at 12～20mg/ml.Further find through screening, when Tween 80 is during in 12～20mg/ml scope, when propylene glycol consumption exceedes 0.3g/ml or ethanol consumption and exceedes 0.3ml/ml, after injection sterilizing, easily occur crystallization.Through further screening and obtain, when Tween 80 consumption is 12～20mg/ml, propylene glycol consumption is 0.001～0.3g/ml; Or Tween 80 consumption is while being 12～20mg/ml, ethanol consumption 0.001～0.3ml/ml, can improve the solubilizing effect of fatsoluble vitamin greatly.Most preferably, Tween 80 consumption is 16mg/ml, and propylene glycol consumption is 0.1g/ml; Or Tween 80 consumption is 16mg/ml, when ethanol consumption is 0.05ml/ml, solubilizing effect the best.
Surprisingly, in the time that solubilizing agent is made to above-mentioned selection, in the first ampoule, in dosage form prescription, can not contain antioxidant, and 13 kinds of Compsoite vitamin injection pharmaceutical composition stability that obtain accordingly are obviously better than 13 kinds of Compsoite vitamin injection pharmaceutical compositions of the prior art.
(2) selection of antioxidant
In order further to improve the stability of the first ampoule injection, in the dosage form prescription of the first ampoule, also can add suitable antioxidant.Research finds, while adding any or theys' any mixture of butylated hydroxyanisole, butylated hydroxytoluene or Radix Gentianae acyl ethanolamine in the first ampoule, the indices of the first ampoule injection obtaining all further improves.Preferably, butylated hydroxyanisole consumption is that 0～0.005mg/ml, butylated hydroxytoluene consumption are that 0～0.02mg/ml, Radix Gentianae acyl ethanolamine consumption are 0～0.04g/ml.
By inventor's above-mentioned research, 13 kinds of Compsoite vitamin injection pharmaceutical compositions that the present invention obtains have following beneficial effect:
(1) do not use antioxidant, the safety of 13 kinds of Compsoite vitamin injection pharmaceutical compositions and the stability that obtain significantly improve compared with prior art.
(2) improved 13 kinds of Compsoite vitamin injection pharmaceutical compositions (no matter whether adding antioxidant) that the present invention obtains, all can adopt the sterilizing of probability of surviving method, and its condition is 115～121 DEG C, and sterilization time is 30～12min; Optimum sterilising conditions is 115 DEG C, 30min or 121 DEG C, and 8min, F0 value reaches 8-12.Improved 13 kinds of Compsoite vitamin injection pharmaceutical compositions of the present invention (no matter whether adding antioxidant), all can be the lower preservation of room temperature (10～30 DEG C) 18 months.Therefore,, compared to prior art, 13 kinds of Compsoite vitamin injection pharmaceutical composition stability that the present invention obtains are significantly improved.
Detailed description of the invention
Below in conjunction with detailed description of the invention, foregoing invention content of the present invention is described in further detail.
But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following embodiment.Without departing from the idea case in the present invention described above, according to ordinary skill knowledge and customary means, make various replacements and change, all should comprise within the scope of the invention.
Embodiment 1
The first ampoule:
Measure fatsoluble vitamin and BHA, BHT are placed in container by prescription, be uniformly mixed, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～4.5 with NaOH, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 4.0～4.5, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 4.5～4.6 with citric acid, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 121 DEG C, 8min sterilizing.
Embodiment 2
The first ampoule:
Measure fatsoluble vitamin and BHA, BHT are placed in container by prescription, be uniformly mixed, then add Tween 80 to continue to be stirred to evenly, obtain oil phase, take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.9～5.0 with NaOH, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filter, oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, NaOH solution with 50% regulates pH to 6～7, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, 115 DEG C, 30min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 5.5～6.0 with citric acid, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 115 DEG C, 30min sterilizing.
Embodiment 3
The first ampoule:
Measure fatsoluble vitamin and BHA, BHT are placed in container by prescription, stir, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.9～5.0 with NaOH, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 5.5～6, and benefit adds to the full amount of water for injection, filter, fill nitrogen, fill, 121 DEG C, 8min sterilizing, this batch of product carried out to stability and keeps sample (at 25 DEG C of temperature), the results are shown in Table 1:
Table 1
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 5.5～6.0 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 121 DEG C, 8min sterilizing.
Embodiment 4
The first ampoule:
Measure fatsoluble vitamin and butylated hydroxytoluene (BHT) is placed in container by prescription, be uniformly mixed, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～4.1 with NaOH, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) and activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 4.0～4.1, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 115 DEG C, 30min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 4.5～4.6 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 115 DEG C, 30min sterilizing.
Embodiment 5
The first ampoule:
Measure fatsoluble vitamin and butylated hydroxyanisole (BHA) is placed in container by prescription, be uniformly mixed, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Taking vitamin C, vitamin B1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B6 by recipe quantity adds the water for injection that is cooled to room temperature and is stirred to dissolving, with NaOH adjusting pH to 4.0～4.5, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filter.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 5.0～5.5, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 115 DEG C, 30min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 4.5～5.0 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 115 DEG C, 30min sterilizing.
Embodiment 6
The first ampoule:
Measure fatsoluble vitamin by prescription and be placed in container, stir, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.5～5.0 with NaOH, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) and activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 6.5～7.0, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 5.5～6.0 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 121 DEG C, 8min sterilizing.
Embodiment 7
The first ampoule:
Measure fatsoluble vitamin by prescription and be placed in container, be uniformly mixed, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6be placed in container, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～4.5 with NaOH, add recipe quantity ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 4.5～5.0, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 5.5～6.0 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; The vitamin B12 of getting recipe quantity adds the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 121 DEG C, 8min sterilizing, this batch of product carried out to stability and keeps sample (at 25 DEG C), the results are shown in Table 2:
Table 2
Embodiment 8
The first ampoule:
Measure fatsoluble vitamin and butylated hydroxyanisole (BHA) is placed in container by prescription, stir, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～4.5 with NaOH, add recipe quantity ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 4.0～4.5 to mend and adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 4.5～4.6 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 121 DEG C, 8min sterilizing.
Embodiment 9
The first ampoule:
Measure fatsoluble vitamin, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) by prescription and be placed in container, stir, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin, Dexpanthenol, nicotiamide, vitamin B
6, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～5.0 with NaOH, add recipe quantity ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) and activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 6.5～7, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 115 DEG C, 30min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 6.5～7 with sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, add in above-mentioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 115 DEG C, 30min sterilizing.
Embodiment 10
The first ampoule:
Measure fatsoluble vitamin and butylated hydroxytoluene (BHT) is placed in container by prescription, be uniformly mixed, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～4.5 with NaOH, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 5.0～5.5, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 4.5～5.0 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 115 DEG C, 30min sterilizing.
Embodiment 11
The first ampoule:
Measure fatsoluble vitamin by prescription and be placed in container, stir, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～5.0 with NaOH, add recipe quantity ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 6.0～7.0, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 6.5～7 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 121 DEG C, 8min sterilizing.
Embodiment 12
The first ampoule:
Measure fatsoluble vitamin by prescription and be placed in container, stir, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin, Dexpanthenol, nicotiamide, vitamin B
6, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～5.0 with NaOH, add recipe quantity ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) and activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 6.0～7.0, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 6.5～7 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 121 DEG C, 8min sterilizing.
Embodiment 13
The first ampoule:
Measure fatsoluble vitamin by prescription and be placed in container, be uniformly mixed, then add Tween 80 to continue to be stirred to evenly, obtain oil phase.Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 4.0～4.5 with NaOH, add recipe quantity propylene glycol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) and activated carbon adsorption, filtration.Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, the NaOH solution with 50% regulates pH to 5.0～5.5, and benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, and 121 DEG C, 8min sterilizing.
The second ampoule:
Take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature of dosing amount cumulative volume 50%, stirring and dissolving under nitrogen protection; Add recipe quantity propylene glycol to stir miscible, adjust pH to 4.5～5.0 with citric acid and sodium citrate, add dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that has been cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, 115 DEG C, 30min sterilizing.
13 kinds of Compsoite vitamin injection pharmaceutical compositions that obtain through technical solution of the present invention, all can carry out 115-121 DEG C of sterilizing, and can meet room temperature (10～30 DEG C) is lower preserve 18 months after indices still meet the requirements.
Claims (9)
1. improved 13 kinds of Compsoite vitamin injections, are divided in two ampoules, and the first ampoule injection contains: vitamin A palmitate, vitamin K
1, vitamin D
3, vitamin E, vitamin C, vitamin B
1, riboflavin sodium phosphate, Dexpanthenol, vitamin B
6, nicotiamide and pH adjusting agent; The second ampoule injection contains: vitamin B
12, folic acid, biotin, stabilizing agent and pH adjusting agent; In the first ampoule injection, contain Tween 80, and any in propylene glycol or ethanol;
It is characterized in that adopting following methods preparation:
(1) first ampoule: measure vitamin A palmitate, vitamin K by prescription
1, vitamin D
3, vitamin E is placed in container, mix homogeneously, adds recipe quantity Tween 80 to continue to be mixed to evenly, obtains oil-phase solution; Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6be placed in container, add the water for injection that is cooled to room temperature and be stirred to dissolving, regulate pH to 3～5 by pH adjusting agent, add recipe quantity propylene glycol or ethanol, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filtration; Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, pH adjusting agent regulates pH to 4～7, and benefit adds to the full amount of water for injection, filtration, fill, sterilizing;
(2) second ampoules: take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature, stirring and dissolving under nitrogen protection; Add recipe quantity stabilizing agent to stir miscible, pH adjusting agent is adjusted pH to 4.5～7, adds dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that is cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, sterilizing.
2. the improved 13 kinds of Compsoite vitamin injections of one according to claim 1, is characterized in that, further contain any or theys' of butylated hydroxyanisole, butylated hydroxytoluene or Radix Gentianae acyl ethanolamine any mixture in described the first ampoule injection.
3. the improved 13 kinds of Compsoite vitamin injections of one according to claim 2, it is characterized in that, described butylated hydroxyanisole consumption is for being less than or equal to 0.005mg/ml, described butylated hydroxytoluene consumption is for being less than or equal to 0.02mg/ml, and described Radix Gentianae acyl ethanolamine consumption is for being less than or equal to 0.04g/ml.
4. according to the improved 13 kinds of Compsoite vitamin injections of the one described in claim 1-3 any one, it is characterized in that, described in the first ampoule injection, the consumption of Tween 80 is 12～20mg/ml, the consumption of described propylene glycol is 0.001～0.3g/ml, and the consumption of described ethanol is 0.001～0.3ml/ml.
5. according to the improved 13 kinds of Compsoite vitamin injections of the one described in claim 1-3 any one, it is characterized in that, the stabilizing agent of described the second ampoule injection is propylene glycol, and wherein the consumption of propylene glycol is 0.001～0.3g/ml.
6. the improved 13 kinds of Compsoite vitamin injections of one according to claim 1, is characterized in that, described the first ampoule injection consists of the following composition: vitamin A palmitate 3300IU, vitamin K
10.15mg, vitamin D
3200IU, vitamin e1 0IU, Catergen 00mg, vitamin B
16mg, riboflavin sodium phosphate 5mg, Dexpanthenol 15mg, vitamin B
66mg, nicotiamide 40mg, Tween 80 12～20mg/ml, and propylene glycol 0.001～0.3g/ml or ethanol 0.001～0.3ml/ml, pH adjusting agent regulates pH value to 4～7;
Described the second ampoule injection consists of the following composition: vitamin B
125 μ g, folic acid 0.6mg, biotin 60 μ g, propylene glycol 0.001～0.3g/ml, pH adjusting agent regulates pH value to 4.5～7.
7. according to the improved 13 kinds of Compsoite vitamin injections of one described in claim 1,2 or 6 any one, it is characterized in that, described in the first ampoule injection, the consumption of Tween 80 is 16mg/ml, and the consumption of described propylene glycol is 0.1g/ml, and the consumption of described ethanol is 0.05ml/ml.
8. according to the improved 13 kinds of Compsoite vitamin injections of one described in claim 1,2 or 6 any one, it is characterized in that, the pH adjusting agent of described the first ampoule injection is sodium hydroxide; The pH adjusting agent of the second described ampoule injection is any or theys' of citric acid or sodium citrate any mixture.
9. the preparation method of the arbitrary described a kind of improved 13 kinds of Compsoite vitamin injections of claim 2-8, is characterized in that, comprises the steps:
(1) first ampoule: measure vitamin A palmitate, vitamin K by prescription
1, vitamin D
3, vitamin E and butylated hydroxyanisole and/or butylated hydroxytoluene be placed in container, mix homogeneously, then adds recipe quantity Tween 80 to continue to be mixed to evenly, obtains oil-phase solution; Take vitamin C, vitamin B by recipe quantity
1, riboflavin sodium phosphate, Dexpanthenol, nicotiamide, vitamin B
6, Radix Gentianae acyl ethanolamine is placed in container, adds the water for injection that is cooled to room temperature and is stirred to dissolving, regulates pH to 3～5 by pH adjusting agent, add propylene glycol or the ethanol of recipe quantity, obtain aqueous phase solution with the filtering with microporous membrane of 0.22 μ m, add 0.03%(w/v) activated carbon adsorption, filter; Oil-phase solution is slowly joined in the aqueous phase solution of rapid stirring, with pH adjusting agent adjusting pH to 4～7, benefit adds to the full amount of water for injection, and filters, fills nitrogen, fill, sterilizing;
(2) second ampoules: take recipe quantity folic acid, biotin, add the water for injection that is cooled to room temperature, stirring and dissolving under nitrogen protection; Add recipe quantity stabilizing agent to stir miscible, pH adjusting agent is adjusted pH to 4.5～7, adds dense part amass 0.05%(W/V) needle-use activated carbon, stirring at normal temperature 15 minutes, decarburization filtration; Get the vitamin B of recipe quantity
12add the water for injection dissolving that is cooled on a small quantity room temperature, join in aforementioned solution, add water for injection to full dose, stir, 0.22 μ m microporous filter membrane fine straining, fill, sealing by fusing, sterilizing.
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| CN201110048015.1A CN102652744B (en) | 2011-03-03 | 2011-03-03 | Modified injection containing 13 compound vitamins and preparation method thereof |
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| CN201110048015.1A CN102652744B (en) | 2011-03-03 | 2011-03-03 | Modified injection containing 13 compound vitamins and preparation method thereof |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104415041B (en) * | 2013-08-23 | 2019-03-12 | 辽宁海思科制药有限公司 | 13 kinds of Compsoite vitamin injection pharmaceutical compositions of one kind and preparation method thereof |
| CN104224820A (en) * | 2014-09-19 | 2014-12-24 | 辽宁海思科制药有限公司 | Pharmaceutical composition containing 13 kinds of multivitamins and preparation method thereof |
| CN108815178A (en) * | 2018-07-30 | 2018-11-16 | 济南康和医药科技有限公司 | One kind containing 13 kinds of Compsoite vitamin injections and its preparation process |
| CN114601846A (en) * | 2020-12-03 | 2022-06-10 | 河北科星药业有限公司 | Complex vitamin amino acid injection for livestock and preparation method and application thereof |
| CN117860668B (en) * | 2023-12-06 | 2024-10-01 | 中润药业有限公司 | Vitamin K1 injection and preparation method and application thereof |
| CN118948759B (en) * | 2024-08-02 | 2025-03-18 | 宝利化（南京）制药有限公司 | A high-stability vitamin B6 injection and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1843362A (en) * | 2006-04-30 | 2006-10-11 | 贵阳云岩西创药物科技开发有限公司 | Composite vitamin injection and its preparation method |
| CN1989975A (en) * | 2005-12-30 | 2007-07-04 | 成都博瑞医药科技开发有限公司 | Method for preparing composite injection of 12 vitamins |
| CN101073580A (en) * | 2007-06-22 | 2007-11-21 | 北京润德康医药技术有限公司 | Compsoite vitamin injection and its production |
| CN101181289A (en) * | 2007-11-28 | 2008-05-21 | 南京海陵中药制药工艺技术研究有限公司 | Injection of 13 kinds complex vitamin and preparing technique thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1989975A (en) * | 2005-12-30 | 2007-07-04 | 成都博瑞医药科技开发有限公司 | Method for preparing composite injection of 12 vitamins |
| CN1843362A (en) * | 2006-04-30 | 2006-10-11 | 贵阳云岩西创药物科技开发有限公司 | Composite vitamin injection and its preparation method |
| CN101073580A (en) * | 2007-06-22 | 2007-11-21 | 北京润德康医药技术有限公司 | Compsoite vitamin injection and its production |
| CN101181289A (en) * | 2007-11-28 | 2008-05-21 | 南京海陵中药制药工艺技术研究有限公司 | Injection of 13 kinds complex vitamin and preparing technique thereof |
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Address after: The 856000 Tibet autonomous region in southern area of Zedang town Xiang Qu Road No. 8 Patentee after: HAISCO PHARMACEUTICAL Group Inc. Patentee after: SICHUAN HAISCO PHARMACEUTICAL Co.,Ltd. Patentee after: LIAONING HAISCO PHARMACEUTICAL Co.,Ltd. Address before: The 856000 Tibet autonomous region in southern area of Zedang town Xiang Qu Road No. 8 Patentee before: TIBET HAISCO PHARMACEUTICAL GROUP Co.,Ltd. Patentee before: SICHUAN HAISCO PHARMACEUTICAL Co.,Ltd. Patentee before: LIAONING HAISCO PHARMACEUTICAL Co.,Ltd. |
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