CN1843362A - Composite vitamin injection and its preparation method - Google Patents
Composite vitamin injection and its preparation method Download PDFInfo
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- CN1843362A CN1843362A CN 200610051040 CN200610051040A CN1843362A CN 1843362 A CN1843362 A CN 1843362A CN 200610051040 CN200610051040 CN 200610051040 CN 200610051040 A CN200610051040 A CN 200610051040A CN 1843362 A CN1843362 A CN 1843362A
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Abstract
The invention provides a composite vitamin injection and its preparing process, wherein the injection is prepared from vitamin A, vitamin C, vitamins D, vitamin E, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6 and right amount of auxiliary materials.
Description
Technical field: the present invention relates to prevention and treat avitaminotic pharmaceutical preparation and preparation method thereof, belong to technical field of medicaments.
Technical background: vitamin is divided into fat-soluble and water solublity 2 big classes by dissolubility usually.Fatsoluble vitamin comprises vitamin A, D, E, 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, the type of preparation of vitamin medicaments is a lot, except that folk prescription and multivitamin compound formulation, also has the compound preparation of a lot of vitamin and mineral and multivitamin and trace element.Wherein the injection compound vitamin has only compound recipe fatsoluble vitamin preparation, as lipomul Vitalipid N Adult and compound recipe soluble vitamin preparation.Fat-soluble and Aquavite preparation all has only oral formulations.Disintegrate is slow, dissolution rate is low, absorption is slow but the oral formulations of vitamin exists, and bioavailability is low, child and coma patient shortcoming such as be difficult for swallowing.And simple fat-soluble or water solublity injection, when the treatment multivitamin lacks and can not be through the patient of the normal feed of digestive tract, mix and to occur the injection muddiness in the process of using, generate suspended matter and increase the liquid medicine contamination probability, the injection that has fat-soluble or water soluble vitamins does not simultaneously appear in the newspapers, and the existing preparation of compound vitamin can not satisfy actual demand.In light of this situation, very be necessary the preparation of compound vitamin is furtherd investigate.
Summary of the invention: the objective of the invention is to: fat-soluble and Aquavite injection liquid drugs injection, powder pin, infusion solution and preparation method thereof are provided; At prior art, the invention provides vitamin C, vitamin A, vitamin D, vitamin B
1, vitamin B
2, vitamin B
3, vitamin B
6, Dexpanthenol (provitamin B
5), vitamin E fat-soluble and Aquavite injection liquid drugs injection, powder pin, the infusion solution formed, solved fat-soluble and the codissolved problem of water soluble vitamins, be particularly suitable for the multivitamin shortage and can not outside the normal patient's who takes food of digestive tract vitamin intestinal, replenish.
The present invention constitutes like this: it is by retinol1 000-3000I.U, vitamin C 50-200mg, vitamin D1 00-400I.U, vitamin E 0.5-2I.U, vitamin B
15-20mg, vitamin B
21-5mg, vitamin B
310-40mg, vitamin B
52-10mg, vitamin B
61-5mg and suitable adjuvant cosolvent are made.
Be preferably: it is by retinol1 500-2500I.U, vitamin C 80-150mg, vitamin D1 50-300I.U, vitamin E 0.5-1.5I.U, vitamin B
18-15mg, vitamin B
22-3mg, vitamin B
315-30mg, vitamin B
53-8mg, vitamin B
62-4mg and suitable adjuvant cosolvent are made.
Say accurately: it is by dehydroretinol 000I.U, vitamin C 100mg, vitamin D2 00I.U, vitamin e1 I.U, vitamin B
110mg, vitamin B
22.54mg, vitamin B
320mg, vitamin B
55mg, vitamin B
63mg and suitable adjuvant cosolvent 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 cosolvent of preparation of the present invention is one or more in Polyethylene Glycol-15-hydroxy stearic acid ester, propylene glycol, hydroxypropyl, soil temperature 80 or the poloxamer.
Say accurately: the cosolvent of described preparation is a propylene glycol, and consumption is 1%.
Injectable sterile block in the preparation of the present invention prepares like this: get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring dissolves sample fully, and 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 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 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 12 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: the Injectable sterile block in the described preparation prepares like this: get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring dissolves sample fully, and press medicine: supplementary product consumption=1: 1 adds 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 ℃, need 1.5 hours approximately, kept this temperature 2 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 12 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 divided to install in the cillin bottle under aseptic condition, gland 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, add 1% propylene glycol again, fully stirring is dissolved sample fully, by volume adds 0.5% active carbon, boils, 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, to 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.
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 1% propylene glycol again, fully stirring dissolves sample fully, 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 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 C, vitamin A, vitamin D, vitamin B are provided
1, vitamin B
2, vitamin B
3, vitamin B
6, Dexpanthenol (provitamin B
5), vitamin E fat-soluble and Aquavite injection liquid drugs injection, powder pin, the infusion solution formed.The inventor has carried out detailed experiments research to the kind and the consumption of cosolvent, has solved fat-soluble and the codissolved problem of water soluble vitamins, and has avoided using cosolvent to cause untoward reaction in a large number; And in the powder ampoule agent for injection process of development vitamin, find, the kind of excipient, consumption, the selection of cooling time is very big to the influence of this preparations shaping property.
The applicant determines that finally cosolvent is a propylene glycol by lot of experiments, and consumption is 1%, excipient is a mannitol, consumption is a medicine: mannitol=1: 1, dry 12 hours, the products obtained therefrom quality was 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.
Hybrid injection of the present invention all is injected directly into liquid condition in tissue, blood vessel or the organ of human body when the clinical practice with vitamin.So absorb soon, effect rapidly.And avoid multi-pass operation to finish the liquid medicine contamination that dosing causes, increase clinical application safety.Be particularly suitable for the multivitamin shortage and can not 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:
Experimental example 1, technical study
1.1 the screening of cosolvent kind:
The test liquid compound method: get vitamin, following cosolvent all adds 1%, and character is observed in an amount of water for injection dissolving.
| Sample number into spectrum | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Cosolvent agent type | Polyethylene Glycol | Polyethylene Glycol-15-hydroxy stearic acid ester | Propylene glycol | Hydroxypropyl | Soil temperature 80 | Poloxamer | Water |
| Dissolution time | 20min | 25min | 10min | 16min | 10min | 20min | 30min |
| Outward appearance behind the placement 2h | Little muddy | Little muddy | Clear and bright | Clear and bright | Clear and bright | Little muddy | Muddy |
As seen, propylene glycol, hydroxypropyl and soil temperature 80 all can make vitamin prescription dissolving of the present invention, consideration hydroxypropyl cost is considered the safety of preparation simultaneously far above soil temperature 80 and propylene glycol, is the best cosolvent of this preparation so select propylene glycol for use.
1.2 the screening of cosolvent consumption:
Test liquid compound method: get vitamin, add 0.1%, 0.5%, 1%, 1.5% propylene glycol, an amount of water for injection dissolving respectively, observe character.
| 0.1% soil temperature 80 | 0.5% soil temperature 80 | 1% soil temperature 80 | 1.5% soil temperature 80 | |
| Test liquid dissolving character | Dissolving does not fully have precipitation | Dissolving does not fully have precipitation | Dissolving is clear and bright fully | Dissolving is clear and bright fully |
As seen, when the consumption of propylene glycol reaches 1%, can be so that vitamin prescription of the present invention dissolving be 1% so select the propylene glycol consumption.
1.3 the screening of injection powder pin excipient and amount of excipient thereof:
Injection powder pin excipient and amount of excipient thereof
| Sample number into spectrum | The excipient type | Vitamin: excipient (g/g) | Outward appearance | The dissolving situation |
| 1 | Glycine | 2∶1 | Off-white color, not full | Jolting 5min dissolving |
| 2 | Glycine | 1∶1 | Off-white color, loose | Jolting 5min dissolving |
| 3 | Glycine | 1∶2 | Off-white color, loose | The jolting dissolving |
| 4 | Mannitol | 2∶1 | Off-white color, loose | The jolting dissolving |
| 5 | Mannitol | 1∶1 | Off-white color, loose | Dissolving rapidly |
| 6 | Mannitol | 1∶2 | Off-white color, loose | Dissolving rapidly |
| 7 | Sodium chloride | 2∶1 | Faint yellow, not full | Jolting 10min dissolving |
| 8 | Sodium chloride | 1∶1 | Faint yellow, loose | Jolting dissolving 5min dissolving |
| 9 | Sodium chloride | 1∶2 | Faint yellow, loose | The jolting dissolving |
| 10 | Lactose | 2∶1 | Off-white color, not full | The jolting dissolving |
| 11 | Lactose | 1∶1 | Off-white color, loose | The jolting dissolving |
| 12 | Lactose | 1∶2 | Off-white color, loose | The jolting dissolving |
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; Conventional excipient has sodium chloride, sodium hydrogen phosphate, mannitol, glycine, lactose etc., find when selecting: glycine, mannitol, sodium chloride and lactose all can make the sample molding according to certain ratio, it is bigger that but the dissolution velocity of manufactured goods differs, in actual applications, the fast product of dissolution velocity has reasonable result of use and clinical value; So we have selected the optimum excipient of the fastest mannitol of dissolution velocity as this product, and consumption is a medicine: mannitol=1: 1.
1.4 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 (40mg/20mg)
| 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 10 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,-45 ℃ freezing 2 hours, evacuation under-45 ℃ of constant temperature slowly heats up, 2～4 ℃/h, time is about 12 hours, continues under the low pressure condition, and it is dry to remove residual moisture to heat up, time is about 12～13 hours, keeps more than 35 ℃ dry 2.5 hours |
Freeze-dry process evaluation of result (40mg/20mg)
| 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 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), Nonavitamine Injection group (water solublity injection be called for short:, the II group), Vtalipid N Adult group (fat-soluble injection 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
8Ml
-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 | IV | The V group |
| 0.5 | 0.235± 0.051 | 0.249± 0.013 | 0.252± 0.022 | 0.303± 0.042 | 0.294± 0.021 |
| 1.5 | 0.241± 0.027 | 0.263± 0.031 | 0.278± 0.014 | 0.318± 0.023 | 0.327± 0.018 |
| 2.5 | 0.239± 0.016 | 0.306± 0.015 | 0.309± 0.201 | 0.345± 0.008 | 0.352± 0.026 |
| 3.5 | 0.238± 0.019 | 0.314± 0.027 | 0.320± 0.053 | 0.414± 0.012 | 0.418± 0.007 |
| 4.5 | 0.237± 0.012 | 0.326± 0.017 | 0.334± 0.018 | 0.336± 0.006 | 0.340± 0.012 |
Compare with matched group, respectively organizing serum in the time of 1～3.5 hour mutually has obvious facilitation to mouse lymphocyte propagation, and injection group of the present invention is effective than Nonavitamine Injection group, Vtalipid N Adult group.
Concrete embodiment:
Embodiment 1: dehydroretinol 000I.U, vitamin C 100mg, vitamin D2 00I.U, vitamin e1 I.U, vitamin B
110mg, vitamin B
22.54mg, vitamin B
320mg, vitamin B
55mg, vitamin B
63mg
Get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring dissolves sample fully, and 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 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 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 12 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 A 2000I.U, vitamin C 100mg, vitamin D 200I.U, vitamin E 1I.U, vitamin B
110mg, vitamin B
22.54mg, vitamin B
320mg, vitamin B
55mg, vitamin B
63mg
Get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring dissolves sample fully, and 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 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 ℃, need 1.5 hours approximately, kept this temperature 2 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 12 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 the Injectable sterile block.
Embodiment 3: dehydroretinol 000I.U, vitamin C 100mg, vitamin D2 00I.U, vitamin e1 I.U, vitamin B
110mg, vitamin B
22.54mg, vitamin B
320mg, vitamin B
55mg, vitamin B
63mg
Get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring is dissolved sample fully, and an amount of water for injection dissolves, and by volume adds 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, and 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: dehydroretinol 000I.U, vitamin C 100mg, vitamin D2 00I.U, vitamin e1 I.U, vitamin B
110mg, vitamin B
22.54mg, vitamin B
320mg, vitamin B
55mg, vitamin B
63mg
Get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring is dissolved sample fully, adds an amount of water for injection dissolving, adds 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, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets glucose intravenous infusion.
Embodiment 5: dehydroretinol 000I.U, vitamin C 100mg, vitamin D2 00I.U, vitamin e1 I.U, vitamin B
110mg, vitamin B
22.54mg, vitamin B
320mg, vitamin B
55mg, vitamin B
63mg
Get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring is dissolved sample fully, adds an amount of water for injection dissolving, adds 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, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets sodium chloride intravenous infusion.
Embodiment 6: retinol1 500I.U, vitamin C 80mg, vitamin D1 50I.U, vitamin E 0.5I.U, vitamin B
18mg, vitamin B
22mg, vitamin B
315mg, vitamin B
53mg, vitamin B
62mg
Get vitamin, add an amount of water for injection dissolving, add Polyethylene Glycol-15-hydroxy stearic acid ester of 1% again, fully stirring is dissolved sample fully, and presses medicine: supplementary product consumption=add lactose 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 30 minutes, coarse filtration, fine straining, install in the enamel tray filtrate branch, 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 divide to install in the cillin bottle under aseptic condition, promptly get the Injectable sterile block.
Embodiment 7: dehydroretinol 500I.U, vitamin C 150mg, vitamin D3 00I.U, vitamin e1 .5I.U, vitamin B
115mg, vitamin B
23mg, vitamin B
330mg, vitamin B
58mg, vitamin B
64mg
Get vitamin, add an amount of water for injection dissolving, add 1% Tween 80 again, fully stirring dissolves sample fully, and press medicine: supplementary product consumption=add mannitol at 2: 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 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,-10 ℃ of pre-freezes 4 hours,-20 ℃ of vacuum dehydrating at lower temperature 10 hours ,-2 ℃ of vacuum dryings 4 hours, 35 ℃ of normal temperature drying 4 hours, under aseptic condition, divide to install in the cillin bottle, promptly get the Injectable sterile block.
Embodiment 8: retinol1 000I.U, vitamin C 50mg, vitamin D1 00I.U, vitamin E 0.5I.U, vitamin B
15mg, vitamin B
21mg, vitamin B
310mg, vitamin B
52mg, vitamin B
61mg
Get vitamin, add an amount of water for injection dissolving, add 1% hydroxypropyl again, fully stirring dissolves sample fully, and press medicine: supplementary product consumption=add sodium chloride 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 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 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 12 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: 3-Hydroxyretinol 000I.U, Catergen 00mg, vitamin D4 00I.U, vitamin E2 I.U, vitamin B
120mg, vitamin B
25mg, vitamin B
340mg, vitamin B
510mg, vitamin B
65mg
Get vitamin, add an amount of water for injection dissolving, add 1% poloxamer again, fully stirring dissolves sample fully, and press medicine: supplementary product consumption=add glycine 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 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 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 12 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.
Claims (10)
1, a kind of composite vitamin injection is characterized in that: it is by vitamin A 1000-3000I.U, vitamin C 50-200mg, vitamin D 100-400I.U, vitamin E 0.5-2I.U, vitamin B
15-20mg, vitamin B
21-5mg, vitamin B
310-40mg, vitamin B
52-10mg and vitamin B
61-5mg and suitable adjuvant cosolvent are made.
2, according to the described composite vitamin injection of claim 1, it is characterized in that: it is by vitamin A 1500-2500I.U, vitamin C 80-150mg, vitamin D 150-300I.U, vitamin E 0.5-1.5I.U, vitamin B
18-15mg, vitamin B
22-3mg, vitamin B
315-30mg, vitamin B
53-8mg and vitamin B
62-4mg and suitable adjuvant cosolvent are made.
3, according to claim 1 or 2 described composite vitamin injections, it is characterized in that: it is by vitamin A 2000I.U, vitamin C 100mg, vitamin D 200I.U, vitamin E 1I.U, vitamin B
110mg, vitamin B
22.54mg, vitamin B
320mg, vitamin B
55mg and vitamin B
63mg and suitable adjuvant cosolvent are made.
4, according to any described composite vitamin injection 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 injection in the claim 1～3, it is characterized in that: the cosolvent of described preparation is one or more in Polyethylene Glycol-15-hydroxy stearic acid ester, propylene glycol, hydroxypropyl, soil temperature 80 or the poloxamer.
6, according to any described composite vitamin injection of claim 5, it is characterized in that: the cosolvent of described preparation is a propylene glycol, and consumption is 1%.
7, preparation method as any described composite vitamin injection in the claim 1～6, it is characterized in that: the Injectable sterile block in the described preparation prepares like this: get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring dissolves sample fully, and press medicine: supplementary product consumption=1: 1 adds 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 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 12 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 injection in the claim 1～6, it is characterized in that: the injectable sterile powder in the described preparation prepares like this: the Injectable sterile block in the described preparation prepares like this: get vitamin, add an amount of water for injection dissolving, add 1% propylene glycol again, fully stirring dissolves sample fully, and press medicine: supplementary product consumption=1: 1 adds 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 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 12 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 injection 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 1% propylene glycol, an amount of water for injection dissolving, by volume add 0.5% needle-use activated 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 injection 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, add 1% propylene glycol again, fully stir and make dissolving fully, add the glucose or the sodium chloride of ormal weight, by volume add 0.5% needle-use activated 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 200610051040 CN1843362A (en) | 2006-04-30 | 2006-04-30 | Composite vitamin injection and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610051040 CN1843362A (en) | 2006-04-30 | 2006-04-30 | Composite vitamin injection and its preparation method |
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| Publication Number | Publication Date |
|---|---|
| CN1843362A true CN1843362A (en) | 2006-10-11 |
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|---|---|---|---|
| CN 200610051040 Pending CN1843362A (en) | 2006-04-30 | 2006-04-30 | Composite vitamin injection and its preparation method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102652744A (en) * | 2011-03-03 | 2012-09-05 | 西藏海思科药业集团股份有限公司 | Modified injection containing 13 compound vitamins and preparation method thereof |
| CN102920670A (en) * | 2012-11-09 | 2013-02-13 | 湖北凤凰白云山药业有限公司 | Preparation method of vitamin C freeze-dried powder |
| CN104337829A (en) * | 2014-05-29 | 2015-02-11 | 西安力邦肇新生物科技有限公司 | Bottled grease micro emulsion freeze-dried preparation with 13 composite vitamins |
-
2006
- 2006-04-30 CN CN 200610051040 patent/CN1843362A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102652744A (en) * | 2011-03-03 | 2012-09-05 | 西藏海思科药业集团股份有限公司 | Modified injection containing 13 compound vitamins and preparation method thereof |
| CN102652744B (en) * | 2011-03-03 | 2014-06-18 | 西藏海思科药业集团股份有限公司 | Modified injection containing 13 compound vitamins and preparation method thereof |
| CN102920670A (en) * | 2012-11-09 | 2013-02-13 | 湖北凤凰白云山药业有限公司 | Preparation method of vitamin C freeze-dried powder |
| CN104337829A (en) * | 2014-05-29 | 2015-02-11 | 西安力邦肇新生物科技有限公司 | Bottled grease micro emulsion freeze-dried preparation with 13 composite vitamins |
| CN104337829B (en) * | 2014-05-29 | 2018-07-27 | 西安力邦肇新生物科技有限公司 | The one bottled compound 13 kinds of vitamin freeze-dried preparations of fat micro emulsion |
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