CN1843359A - Composite vitamin pharmaceutical formulation and its preparation method - Google Patents
Composite vitamin pharmaceutical formulation and its preparation method Download PDFInfo
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- CN1843359A CN1843359A CN 200610051041 CN200610051041A CN1843359A CN 1843359 A CN1843359 A CN 1843359A CN 200610051041 CN200610051041 CN 200610051041 CN 200610051041 A CN200610051041 A CN 200610051041A CN 1843359 A CN1843359 A CN 1843359A
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Abstract
The invention provides a composite vitamin medicinal preparation and its preparing process, which comprises vitamin B1, vitamin B2, vitamin B6, vitamin B3, vitamin B12, vitamin B5, vitamin C and right amount of auxiliary materials.
Description
Technical field: the present invention relates to prevention and treat avitaminotic injection preparation and preparation method thereof, belong to technical field of medicaments.
Technical background: water soluble vitamins comprises vitamin B group and vitamin C, they keep human body normal physiological function and matter energy metabolism, be one of human body six big nutritional factorss, most of vitamin must obtain from food, only can synthesize in vivo or be produced by intestinal bacteria on a small quantity.When intake deficiency, malabsorption or disease, provitamin changes when being obstructed, and all can cause the vitamin deficiency of human body.
At present, water soluble vitamins has ejection preparation, and as Nonavitamine Injection, Xin Wei (Vitamin H), but the former contains biotin and glycine, and the latter is also contained folic acid.Now, along with growth in the living standard, people more and more pay attention to vitimin supplement, but also there are the mistaken ideas on some understanding, although vitamin is good for health in fact, but be not endlessly to take, the kind that is not vitamin is The more the better, amount is the bigger the better, and vitimin supplement should " be taken what one needs ", as long-term a large amount of oral vitamins, accumulate in a large number in the body, even cause poisoning, and some vitamin can individual produce untoward reaction to some, allergy occurs after being reported in oral folic acid as the minority case.
The inventor has carried out experimentation to the prescription of compound water soluble vitamins, found that vitamin B
1, vitamin B
2, vitamin B
6, vitamin B
3, vitamin B
12, vitamin B
5, vitamin C is the easily vitamin kind of disappearance of human body, and discovers vitamin B
1, vitamin B
2, vitamin B
6, vitamin B
3, vitamin B
12, vitamin B
5, ascorbic composing prescription preparation function well that immunologic function is improved, compare with Nonavitamine Injection, Xin Wei (Vitamin H), not only can reduce production costs, prior under the prerequisite of same function, reduce dose, improve safety.
Summary of the invention: the objective of the invention is to: vitamin B is provided
1, vitamin B
2, vitamin B
6, vitamin B
3, vitamin B
12, vitamin B
5, ascorbic injection liquid drugs injection, powder pin, infusion solution and preparation method thereof; The present invention is directed to prior art, vitamin B is provided
1, vitamin B
2, vitamin B
6, vitamin B
3, vitamin B
12, vitamin B
5, vitamin C injection liquid drugs injection, powder pin, the infusion solution formed, be suitable for and can not outside the patient's of the normal feed of digestive tract vitamin intestinal, replenish.
The present invention constitutes like this: it is by vitamin B
120-60mg, vitamin B
23-10mg, vitamin B
65-20mg, vitamin B
380-300mg, vitamin B
122-8mcg, vitamin B
55-20mg, vitamin C 100-400mg and suitable auxiliary material excipient are made.
Be preferably: it is by vitamin B
130-50mg, vitamin B
25-8mg, vitamin B
68-15mg, vitamin B
3100-200mg, vitamin B
123-6mcg, vitamin B
58-15mg, vitamin C 150-250mg and suitable auxiliary material excipient are made.
Say accurately: it is by vitamin B
140mg, vitamin B
27.6mg, vitamin B
610mg, vitamin B
3150mg, vitamin B
124mcg, vitamin B
510mg, Catergen 00mg and suitable auxiliary material excipient are made.
Preparation of the present invention be directly used in the injection of drug administration by injection, directly for the venous transfusion of intravenous drip, need be used for the concentrated solution for injection of intravenous drip and injectable sterile powder and the aseptic block that makes with freeze-drying or spray drying method after the dilution.
The excipient of injectable sterile powder of the present invention and aseptic block preparation is one or more in mannitol, lactose, sucrose, glucose, glycine, the sodium chloride.
Say accurately: the excipient of described injectable sterile powder and aseptic block preparation is a mannitol.
Injectable sterile block in the preparation of the present invention prepares like this: get vitamin, press medicine: supplementary product consumption=1: 1.5 adding mannitol, add an amount of water for injection stirring and make dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, the filtrate packing, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, gland, promptly.
Injectable sterile powder in the preparation of the present invention prepares like this: get vitamin, press medicine: supplementary product consumption=1: 1.5 adding mannitol, add an amount of water for injection stirring and make dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, install in the enamel tray filtrate branch, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, and under aseptic condition, divided to install in the cillin bottle, promptly.
Injection and concentrated solution for injection in the preparation of the present invention prepare like this: get vitamin, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, boils, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining add the injection water, divide to install to pacify and cut open bottle, seal sterilization, promptly.
Glucose or sodium chloride intravenous infusion in the preparation of the present invention prepare like this: get vitamin, add an amount of water for injection dissolving, add the glucose or the sodium chloride of ormal weight, by volume add 0.5% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, the saturated sodium hydroxide solution of reuse adjust pH to 7.0～7.5, boil, 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add the injection water, packing, sterilization promptly.
Compared with prior art, the present invention is directed to prior art, vitamin B is provided
1, vitamin B
2, vitamin B
6, vitamin B
3, vitamin B
12, vitamin B
5, ascorbic injection liquid drugs injection, powder pin, infusion solution and preparation method thereof; The inventor the development vitamin the powder ampoule agent for injection process in find, in the preparation process, the kind of excipient, consumption, the selection of cooling time is very big to the influence of this preparations shaping property.
The applicant passes through lot of experiments, final determine that mannitol cooked excipient, consumption is a medicine: mannitol=1: 1.5,0 ℃ of pre-freeze 2 hours,-18 ℃ freezing 2 hours, the back is reduced to-45 ℃ in 1.5h, and freezing 2.5 hours, 3 ℃ of vacuum dryings 10 hours, dry 12h heats up, 35 ℃ of normal temperature drying 2.5 hours, the products obtained therefrom quality is loose, and adding behind the water rapidly, dissolving returns to the original characteristic of medicinal liquid; Water content is low, is difficult for oxidation, helps the product long term store; Dosage is accurate, good appearance; Good stability, safe, evident in efficacy.Injection vitamin of the present invention all is injected directly in tissue, blood vessel or the organ of human body with liquid condition when clinical practice.So absorb soon, effect rapidly.Be suitable for and outside the normal patient's who takes food of digestive tract vitamin intestinal, replenish.
For proving that medicine provided by the invention has effective effect, the applicant has carried out a series of experiments:
The screening of experimental example 1,1.1 injection powder pin excipient and amount of excipient thereof:
Injection powder pin categories of excipients
| Sample number into spectrum | The excipient type | Vitamin: excipient (g/g) | Outward appearance | The dissolving situation |
| 1 | Glycine | 1∶3 | Off-white color, loose | The jolting dissolving |
| 2 | Glycine | 1∶1.5 | Off-white color, loose | Jolting 5min dissolving |
| 3 | Glycine | 1∶1 | Off-white color, not full | Jolting 5min dissolving |
| 4 | Mannitol | 1∶3 | Off-white color, loose | Dissolving rapidly |
| 5 | Mannitol | 1∶1.5 | Off-white color, loose | Dissolving rapidly |
| 6 | Mannitol | 1∶1 | Off-white color, loose | The jolting dissolving |
| 7 | Sodium chloride | 1∶3 | Off-white color, loose | Jolting 5min dissolving |
| 8 | Sodium chloride | 1∶1.5 | Off-white color, not full | Jolting 5min dissolving |
| 9 | Sodium chloride | 1∶1 | Off-white color, not full | Jolting 5min dissolving |
| 10 | Lactose | 1∶3 | Off-white color, loose | The jolting dissolving |
| 11 | Lactose | 1∶1.5 | Off-white color, loose | The jolting dissolving |
| 12 | Lactose | 1∶1 | Off-white color, not full | The jolting dissolving |
The screening of mannitol consumption
| Sample number into spectrum | The excipient type | Vitamin: excipient (g/g) | Outward appearance | The dissolving situation |
| 1 | Mannitol | 1∶0.5 | Off-white color, not full | Jolting 5min dissolving |
| 2 | Mannitol | 1∶1 | Off-white color, loose | The jolting dissolving |
| 3 | Mannitol | 1∶1.5 | Off-white color, loose | Dissolving rapidly |
| 4 | Mannitol | 1∶2 | Off-white color, loose | Dissolving rapidly |
| 5 | Mannitol | 1∶2.5 | Off-white color, loose | Dissolving rapidly |
| 6 | Mannitol | 1∶3 | Off-white color, loose | Dissolving rapidly |
For selecting for use mannitol to do excipient, be that the applicant is selected after carrying out a series of experiments, definite among the present invention; Select different excipient for use, the dissolution velocity of manufactured goods differs bigger, and in actual applications, the fast product of dissolution velocity has reasonable result of use and clinical value; So we have selected the excipient of the fastest mannitol of dissolution velocity as this product, and consumption is a medicine: mannitol=1: 1.5.
1.2 the selection of freeze-dry process:
Freezing dry process comprises pre-freeze, distillation and dry again three phases.The freeze-dry process that adopts has designed three kinds of lyophilisation conditions altogether and has tested when screening with reference to excipient, and relatively every index of dried frozen aquatic products under three kinds of lyophilisation conditions is selected best freeze-dry process.
The selection of freeze-dry process
| Technology one | -10 ℃ of pre-freezes 2 hours,-25 ℃ freezing 3 hours,-25 ℃ of vacuum dehydrating at lower temperature 15 hours ,-2 ℃ of vacuum dryings 5 hours, 30 ℃ of normal temperature drying 2 hours |
| Technology two | -30 ℃ of pre-freezes 4 hours ,-20 ℃ of vacuum dehydrating at lower temperature 18 hours ,-2 ℃ of vacuum dryings 4 hours, 35 ℃ of normal temperature drying 4 hours |
| Technology three | 0 ℃ of pre-freeze 2 hours,-18 ℃ freezing 2 hours, the back is reduced to-45 ℃ in 1.5h, freezing 2.5 hours,-45 ℃ of beginning evacuation, programming rate be 2～4 degree/hour, vacuum drying 22 hours, 35 ℃ of normal temperature drying 2.5 hours |
The freeze-dry process evaluation of result
| Technology one | It is poor slightly to freeze type, and a little sample surfaces has the crack, and the phenomenon of caving in is arranged, the water content height |
| Technology two | It is poor slightly to freeze type, and some sample surfaces has bubbling, and water content is higher |
| Technology three | It is better to freeze type, and water content is low |
As seen from the experiment: the pre-freeze temperature is low excessively, the easy crack of sample surfaces; Cooling time is too short, easily causes sample freezing not exclusively, and occurs bubbling when causing vacuum drying.Technology one and technology two water content are higher.Technology three has been improved preferably and has been frozen type, determines that therefore technology three is as the freeze dried process conditions of this product.
Experimental example 2, preparation of the present invention are to the influence of mice immune function of mice (spleen lymphocyte proliferation activity):
Body weight is 18～20gBALB/c mice, male and female at random, be divided into normal saline group (blank group at random by body weight, the I group), the Nonavitamine Injection group (is called for short: the II group), Xin Wei (Vitamin H group be called for short:, be called for short: the III group), injection group of the present invention (be called for short: the IV group), injection powder pin group of the present invention (be called for short: the V group), every group 50 respectively.The common cubed feed of feeding, ad lib drinking-water, more than all adopt lumbar injection.The ether inhalation anesthesia respectively in 0.5,1.5,2.5,3.5 and 4.5 hour of injection back is plucked eyeball and is got blood (each time 10 mutually) under the aseptic condition, separation of serum (2700r/min, 10 minutes), and 56 ℃ of deactivations in 30 minutes, 4 ℃ of preservations are standby.Matched group prepares serum with identical method and preserves.Get of the same age female/2 of mices, taking off neck puts to death, in 75% ethanol cylinder submergence 1 minute, aseptic taking-up spleen is put on the 100 order nylon wires, adds a small amount of 0.01mol/LPBS and smearing dispersion equipment gently, make individual cells fully enter in the buffer, centrifugal 10 minutes of 800r/min abandons supernatant, adds erythrocyte cracked liquid (0.1mol/LTris-NH
4Cl) 5ml left standstill 5 minutes, the centrifugal supernatant of abandoning, and PBS washing 3 times, standardize solution, mirror is counting down, and it is 5 * 10 that RPMI1640 cultivates keynote cell suspension
6Ml
-1Get 96 well culture plates, every hole adds the not test serum of phase simultaneously of 100ul splenocyte suspension, 100ul2.5ul/mlConA20ul respectively, 4 multiple holes; Control wells adds normal control serum 20ul, 4 multiple holes.37 ℃, 5%CO
2Cultivated 72 hours, and cultivated and finish preceding 4 hours every hole adding MTT10ul, cultivate and finish the centrifugal supernatant of abandoning, every hole adds DMSO100ul, and vibration is 20 minutes on shaking table, microplate reader survey A
570nmValue.
Preparation of the present invention is to the active influence (A of mice spleen lymphocytes proliferation
570nm, X ± S)
| Time (h) | The I group | The II group | The III group | The IV group | The V group |
| 0.5 | 0.229± 0.024 | 0.240± 0.036 | 0.244± 0.014 | 0.242± 0.022 | 0.245± 0.033 |
| 1.5 | 0.236± 0.015 | 0.257± 0.029 | 0.265± 0.021 | 0.263± 0.015 | 0.267± 0.012 |
| 2.5 | 0.235± 0.027 | 0.312± 0.043 | 0.296± 0.201 | 0.305± 0.018 | 0.313± 0.014 |
| 3.5 | 0.234± 0.006 | 0.320± 0.013 | 0.322± 0.031 | 0.322± 0.017 | 0.325± 0.016 |
| 4.5 | 0.236± 0.008 | 0.322± 0.007 | 0.332± 0.010 | 0.330± 0.015 | 0.341± 0.022 |
With matched group relatively, respectively organizing serum in the time of 1～3.5 hour mutually has obvious facilitation to mouse lymphocyte propagation, injection group of the present invention and Nonavitamine Injection group, that Xin Wei (Vitamin H) organizes effect is suitable.
Concrete embodiment:
Embodiment 1: vitamin B
140mg, vitamin B
27.6mg, vitamin B
610mg, vitamin B
3150mg, vitamin B
124mcg, vitamin B
510mg, Catergen 00mg
Get vitamin, press medicine: supplementary product consumption=add mannitol at 1: 1.5 adds an amount of water for injection stirring and makes dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, the filtrate packing, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, gland promptly gets the Injectable sterile block.
Embodiment 2: vitamin B
140mg, vitamin B
27.6mg, vitamin B
610mg, vitamin B
3150mg, vitamin B
124mcg, vitamin B
510mg, Catergen 00mg
Get vitamin, press medicine: supplementary product consumption=add mannitol at 1: 1.5 adds an amount of water for injection stirring and makes dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, install in the enamel tray filtrate branch, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, need 1.5 hours approximately, kept this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature, slowly heat up, 2～4 ℃/h, to the lowest total of the melting point temperature, time is about 10 hours, after sublimation drying is finished, continue under the low pressure condition, it is dry to remove residual moisture to heat up, time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, and under aseptic condition, divided to install in the cillin bottle, promptly get injectable sterile powder.
Embodiment 3: vitamin B
140mg, vitamin B
27.6mg, vitamin B
610mg, vitamin B
3150mg, vitamin B
124mcg, vitamin B
510mg, Catergen 00mg
Get vitamin, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, boils, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining add the injection water, divide to install to pacify and cut open bottle, seal sterilization, promptly get injection and concentrated solution for injection.
Embodiment 4: vitamin B
140mg, vitamin B
27.6mg, vitamin B
610mg, vitamin B
3150mg, vitamin B
124mcg, vitamin B
510mg, Catergen 00mg
Get vitamin, add an amount of water for injection dissolving, add the glucose of ormal weight, by volume add 0.5% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, the saturated sodium hydroxide solution of reuse adjust pH to 7.0～7.5, boil, 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add the injection water, packing, sterilization promptly gets glucose intravenous infusion.
Embodiment 5: vitamin B
140mg, vitamin B
27.6mg, vitamin B
610mg, vitamin B
3150mg, vitamin B
124mcg, vitamin B
510mg, Catergen 00mg
Get vitamin, add an amount of water for injection dissolving, add the sodium chloride of ormal weight, by volume add 0.5% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, the saturated sodium hydroxide solution of reuse adjust pH to 7.0～7.5, boil, 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add the injection water, packing, sterilization promptly gets sodium chloride intravenous infusion.
Embodiment 6: vitamin B
130mg, vitamin B
25mg, vitamin B
68mg, vitamin B
3100mg, vitamin B
123mcg, vitamin B
58mg, vitamin C 150mg
Get vitamin, press medicine: supplementary product consumption=1: 1.2 adding lactose, add an amount of water for injection stirring and make dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, install in the enamel tray filtrate branch, lyophilization ,-10 ℃ of pre-freezes 4 hours ,-20 ℃ of vacuum dehydrating at lower temperature 18 hours,-2 ℃ of vacuum dryings 4 hours, 35 ℃ of normal temperature drying 4 hours divide to install in the cillin bottle under aseptic condition, promptly get injectable sterile powder.
Embodiment 7: vitamin B
150mg, vitamin B
28mg, vitamin B
615mg, vitamin B
3200mg, vitamin B
126mcg, vitamin B
515mg, Catergen 50mg
Get vitamin, press medicine: supplementary product consumption=1: 1 adding sucrose, add an amount of water for injection stirring and make dissolving,, add the injection water to ormal weight with saturated sodium hydroxide solution adjust pH to 6.5～7.0, mixing, the needle-use activated carbon of adding 0.5% boiled coarse filtration 30 minutes, fine straining, filtrate is divided and to be installed in the enamel tray, lyophilization ,-10 ℃ of pre-freezes 2 hours,-15 ℃ freezing 3 hours,-35 ℃ of vacuum dehydrating at lower temperature 15 hours ,-2 ℃ of vacuum dryings 5 hours, 30 ℃ of normal temperature drying 2 hours, under aseptic condition, divide to install in the cillin bottle, promptly get injectable sterile powder.
Embodiment 8: vitamin B
120mg, vitamin B
23mg, vitamin B
65mg, vitamin B
380mg, vitamin B
122mcg, vitamin B
55mg, vitamin C 100mg
Get vitamin, press medicine: supplementary product consumption=add glucose at 1: 2 adds an amount of water for injection stirring and makes dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, the filtrate packing, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, gland promptly gets the Injectable sterile block.
Embodiment 9: vitamin B
160mg, vitamin B
210mg, vitamin B
620mg, vitamin B
3300mg, vitamin B
128mcg, vitamin B
520mg, vitamin C 400mg get vitamin, press medicine: supplementary product consumption=add sodium chloride at 1: 2.5 adds an amount of water for injection stirring and makes dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, the filtrate packing, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, gland promptly gets the Injectable sterile block.
Embodiment 10: vitamin B
160mg, vitamin B
210mg, vitamin B
620mg, vitamin B
3300mg, vitamin B
128mcg, vitamin B
520mg, vitamin C 400mg
Get vitamin, press medicine: supplementary product consumption=add glycine at 1: 1.5 adds an amount of water for injection stirring and makes dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5%, boiled coarse filtration, fine straining 30 minutes, the filtrate packing, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, gland promptly gets the Injectable sterile block.
Embodiment 11: vitamin B
160mg, vitamin B
210mg, vitamin B
620mg, vitamin B
3300mg, vitamin B
128mcg, vitamin B
520mg, vitamin C 400mg
Get vitamin, press medicine: supplementary product consumption=add mannitol at 1: 1 adds an amount of water for injection stirring and makes dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water and be made into 3% solution, stirring and evenly mixing adds 0.5% needle-use activated carbon, boiled 30 minutes, coarse filtration, fine straining is 160 ℃ in inlet temperature, leaving air temp is 50 ℃, and air velocity is 25ms
-1Condition under spray drying get powder, packing, sterilized powder.
Claims (10)
1, a kind of composite vitamin pharmaceutical formulation is characterized in that: it is by vitamin B
120-60mg, vitamin B
23-10mg, vitamin B
65-20mg, vitamin B
380-300mg, vitamin B
122-8mcg, vitamin B
55-20mg and vitamin C 100-400mg and suitable auxiliary material excipient are made.
2, according to the described composite vitamin pharmaceutical formulation of claim 1, it is characterized in that: it is by vitamin B
130-50mg, vitamin B
25-8mg, vitamin B
68-15mg, vitamin B
3100-200mg, vitamin B
123-6mcg, vitamin B
58-15mg and vitamin C 150-250mg and suitable auxiliary material excipient are made.
3, according to claim 1 or 2 described composite vitamin pharmaceutical formulations, it is characterized in that: it is by vitamin B
140mg, vitamin B
27.6mg, vitamin B
610mg, vitamin B
3150mg, vitamin B
124mcg, vitamin B
510mg and vitamin C 200mg and suitable auxiliary material excipient are made.
4, according to any described composite vitamin pharmaceutical formulation in the claim 1～3, it is characterized in that: described preparation be directly used in the injection of drug administration by injection, directly for the venous transfusion of intravenous drip, need be used for the concentrated solution for injection of intravenous drip and injectable sterile powder and the aseptic block that makes with freeze-drying or spray drying method after the dilution.
5, according to any described composite vitamin pharmaceutical formulation in the claim 1～4, it is characterized in that: the excipient of described injectable sterile powder and aseptic block preparation is one or more in mannitol, lactose, sucrose, glucose, glycine or the sodium chloride.
6, according to the described composite vitamin pharmaceutical formulation of claim 5, it is characterized in that: the excipient of described injectable sterile powder and aseptic block preparation is a mannitol.
7, preparation method as any described composite vitamin pharmaceutical formulation in the claim 1～6, it is characterized in that: the Injectable sterile block in the described preparation prepares like this: get vitamin, press medicine: supplementary product consumption=1: 1.5 adding mannitol, add an amount of water for injection stirring and make dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5% boiled 30 minutes, coarse filtration, fine straining, filtrate packing, lyophilization, equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, gland, promptly.
8, preparation method as any described composite vitamin pharmaceutical formulation in the claim 1～6, it is characterized in that: the injectable sterile powder in the described preparation prepares like this: get vitamin, press medicine: supplementary product consumption=1: 1.5 adding mannitol, add an amount of water for injection stirring and make dissolving, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, add the injection water to ormal weight, mixing, the needle-use activated carbon of adding 0.5% boiled 30 minutes, coarse filtration, fine straining, install in the enamel tray lyophilization filtrate branch, equilibration time when the balance solidification point of phase I is 0 ℃ is 2 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-18 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-45 ℃, needs 1.5 hours approximately, keeps this temperature 2.5 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-45 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 10 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 12～13 hours, kept more than 35 ℃ dry 2.5 hours, and under aseptic condition, divided to install in the cillin bottle, promptly.
9, as the preparation method of any described composite vitamin pharmaceutical formulation in the claim 1～6, it is characterized in that: injection and concentrated solution for injection in the described preparation prepare like this: get vitamin, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, with saturated sodium hydroxide solution adjust pH to 6.5～7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, divide to install to pacify and cut open bottle, seal sterilization, promptly.
10, preparation method as any described composite vitamin pharmaceutical formulation in the claim 1～6, it is characterized in that: glucose or sodium chloride intravenous infusion in the described preparation prepare like this: get vitamin, add an amount of water for injection dissolving, the glucose or the sodium chloride that add ormal weight, by volume add 0.5% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, boil the saturated sodium hydroxide solution of reuse adjust pH to 7.0～7.5, and 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization is promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610051041 CN1843359A (en) | 2006-04-30 | 2006-04-30 | Composite vitamin pharmaceutical formulation and its preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610051041 CN1843359A (en) | 2006-04-30 | 2006-04-30 | Composite vitamin pharmaceutical formulation and its preparation method |
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| CN1843359A true CN1843359A (en) | 2006-10-11 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1957890B (en) * | 2006-10-17 | 2010-06-23 | 颜怀伟 | Composite vitamine product for local increasing fat safely, and fabricating method |
| CN103340891A (en) * | 2013-06-08 | 2013-10-09 | 哈尔滨珍宝制药有限公司 | B vitamins containing composition and preparation method thereof |
-
2006
- 2006-04-30 CN CN 200610051041 patent/CN1843359A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1957890B (en) * | 2006-10-17 | 2010-06-23 | 颜怀伟 | Composite vitamine product for local increasing fat safely, and fabricating method |
| CN103340891A (en) * | 2013-06-08 | 2013-10-09 | 哈尔滨珍宝制药有限公司 | B vitamins containing composition and preparation method thereof |
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