CN101366712B - Method for preparing fat-soluble vitamin for injection - Google Patents
Method for preparing fat-soluble vitamin for injection Download PDFInfo
- Publication number
- CN101366712B CN101366712B CN2008102230464A CN200810223046A CN101366712B CN 101366712 B CN101366712 B CN 101366712B CN 2008102230464 A CN2008102230464 A CN 2008102230464A CN 200810223046 A CN200810223046 A CN 200810223046A CN 101366712 B CN101366712 B CN 101366712B
- Authority
- CN
- China
- Prior art keywords
- vitamin
- injection
- fat
- solution
- weight portion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a method for preparing fat soluble vitamins for injection. The fat soluble vitamins for injection contain vitamin A palmitate, vitamin D2, vitamin E, vitamin K1 and pharmaceutically acceptable supplementary materials. Sterile freeze-dried powder prepared by the fat soluble vitamins for injection through the low-pressure freeze-drying technology can simultaneously compensate all the four fat soluble vitamins through veins, and simultaneously can be dissolved in water-soluble diluent after special technological treatment, thus fat emulsion is not necessarily adopted as the diluent and the problem of inconvenience that the use of the fat soluble vitamins by patients is limited by the diluent is solved.
Description
Technical field
The present invention relates to medical technical field, more specifically to a kind of preparation method of fat-soluble vitamin for injection.
Background technology
Vitamin is keeping the benefit aspect health and the prevent disease to be confirmed gradually, and multivitamin not only can be used as main or adjuvant therapy medicaments is applied to clinically, also can be used as dietary supplement and promotes health, prevent disease.Along with the continuous increase of nourishing reinforced food and dietary supplement kind and quantity, issuable ill effect also comes into one's own certain vitamin of excess ingestion (fatsoluble vitamin that cumulative action is arranged especially in vivo) day by day to body.
Vitamin is divided into water soluble vitamins and fatsoluble vitamin by the difference of dissolution properties, and wherein fatsoluble vitamin comprises altogether: A, D; E; four kinds of K to keeping body metabolism and function is indispensable, supply the normal function that vitamin helps the rehabilitation of disease and keeps human body.When the patient because of temporarily not taking food after performing the operation, than large-area burns, severe infections, hyperpyrexia, chemotherapy of tumors, long-term diarrhea, necrotic colitis and other reasons cause in the time of temporarily can not taking food, all can when vein replenishes liquid, add the necessary fat-soluble vitamin for injection of human body, carry out additional comprehensively to the scarce fatsoluble vitamin of body institute.
It is different that fatsoluble vitamin and water soluble vitamins are gone up in some respects, and fatsoluble vitamin often is present in the oils and fats part of fat and food, so because not soluble in water can only digesting and assimilating in bile.The aseptic freeze-dried powder that fat-soluble vitamin for injection is made through the lyophilized technology, can replenish whole four kinds of fatsoluble vitamiies simultaneously through vein, handle through special process simultaneously, be dissolvable in water the water solublity diluent, as: glucose, in the transfusion such as sodium chloride, needn't in the selection of diluent, must adopt fat milk, solve the patient and used fatsoluble vitamin to be subjected to the inconvenience of diluent restriction.
Summary of the invention
The present invention relates to a kind of preparation method of fat-soluble vitamin for injection.Fat-soluble vitamin for injection of the present invention contains vitamin A palmitate, vitamin D
2, vitamin E, vitamin K
1And acceptable accessories.The aseptic freeze-dried powder that fat-soluble vitamin for injection of the present invention is made through the lyophilized technology, can replenish whole four kinds of fatsoluble vitamiies simultaneously through vein, handle through special process simultaneously, be dissolvable in water the water solublity diluent, needn't in the selection of diluent, must adopt fat milk, solve the patient and used fatsoluble vitamin to be subjected to the inconvenience of diluent restriction.
The fat-soluble vitamin for injection prescription:
Vitamin A palmitate 1.5-2.5 weight portion
Vitamin D
2The 3-8 weight portion
Vitamin E 7-10 weight portion
Vitamin K
1The 130-180 weight portion
Tween 80 40-60 weight portion
Polysorbas20 0.5-1.5 weight portion
Ethanol 250-400 weight portion
Glycine 2-3 weight portion
Cysteine hydrochloride 0.3-0.8 weight portion
Sodium sulfite 2-4 weight portion
EDTA-2Na 0.3-0.8 weight portion
Mannitol 40-60 weight portion
Fat-soluble vitamin for injection technology:
(1) EDTA-2Na that takes by weighing recipe quantity adds in the 75-90% water for injection (25 ℃ of water temperatures), is stirred to whole dissolvings, and inflated with nitrogen carries out saturatedly, obtains solution A, and is standby;
(2) mannitol, glycine, cysteine hydrochloride, the sodium sulfite that takes by weighing recipe quantity joins in the solution A, is stirred to whole dissolvings, and adjusting pH is 5.0-7.0, adds recipe quantity ethanol, stirs, and obtains solution B, and be standby;
(3) take by weighing the recipe quantity vitamin D
2, put in the beaker, add 1-4ml ethanol, make dissolving, obtain solution C, standby;
(4) take by weighing recipe quantity vitamin E, Tween 80, polysorbas20, vitamin K successively
1, vitamin A palmitate, put in the beaker, stir and made dissolving in 8-12 minute, add in the solution C,, to same beaker, continue to stir and made dissolving in 30-50 minute with 1-5ml ethanol gradation cleaning solution C beaker, obtain solution D, standby;
(5) slowly pour into solution B, solution D in the agitator tank, constantly stir simultaneously, and water is rinsed beaker well, fully after the dissolving, regulate pH value between 6-7 with the NaOH solution of 0.1mol/L or the HCL solution of 0.1mol/L, benefit adds to the full amount of water for injection, and adds 0.05% (g/ml) active carbon, stirring at room 20-40 minute, coarse filtration was taken off charcoal; Survey pH value and intermediate content, carry out aseptic filter pressing after qualified;
(6) liquid medicine filling: indoor hundred grades of clean packing, micropore filter by 0.22 μ m to the aseptic filtration of medicinal liquid twin-stage after, be delivered to the numerical control liquid-filling machine, carry out liquid medicine filling according to the medicinal liquid loading amount, and carry out automatic false add plug, then semi-finished product are put on the clean freeze drying box internal partition, from top to bottom put successively, the products temperature gauge head is placed in required thermometric position on request, shuts chamber door then, medicinal liquid is carried out lyophilization;
(7) lyophilizing: medicine is put into case before the freeze dryer, closes chamber door, drive cold before case, when products temperature being reduced to-40 ℃, be incubated 2 hours, begin cold rear cabinet, when the rear cabinet temperature is chilled to below-45 ℃, the beginning evacuation when vacuum arrives 8～10Pa, begins to heat up.Begin to heat up from-40 ℃, the plate temperature heats up with the per 30 minutes speed with 5 ℃ below-25 ℃ the time; Insulation is 1 hour when arriving-20 ℃; Insulation is 2 hours when arriving-15 ℃; Insulation is 2 hours when arriving-10 ℃; Insulation is 2 hours when arriving-5 ℃; Insulation is 1 hour when arriving 0 ℃, observes goods watermark disappearance situation later on, progressively heats up, and products temperature arrives 20 ℃, is incubated 6 hours;
(8) fill nitrogen: lyophilization finishes, and connects the nitrogen pipeline through 0.22 μ m filter aseptic filtration, fills nitrogen.For the first time being filled to vacuum (probably needs 5-6MPa) when 650mbar, when being evacuated to the 10Pa left and right sides again, be filled to vacuum when 950mbar for the second time; Filling finish in cold dried case, carry out automatic tamponade under the condition of partial vacuum after, open charging valve and inflate, inflation is opened chamber door after finishing, and takes out the temperature of articles gauge head, from bottom to top presses the opposite order outlet of inlet.
Weight portion in the fat-soluble vitamin for injection prescription of the present invention is meant dosage unit commonly used in the pharmacy, as g, and mg, 1ml.
The preparation technology of fat-soluble vitamin for injection of the present invention all carries out under the lucifuge operation.
Data are investigated in fat-soluble vitamin for injection (II) test
One, influence factor's test:
Get this product, by " Chinese pharmacopoeia version appendix in 2005 XIXC requirement carrying out high temperature (40 ℃, 60 ℃) and strong illumination (4500 ± 500LX) tests, result of the test sees Table 1,2,3:
Table 1 influence factor high temperature (40 ℃) result of the test
Table 2 influence factor high temperature (60 ℃) result of the test
Table 3 influence factor illumination (4500 ± 500LX) result of the tests
Two, accelerated test:
Get this product by commercially available back, place under 40 ℃ ± 2 ℃, the condition of relative humidity RH75% ± 5% and placed 6 months, test in duration of test sampling in the 1st, 2,3,6 months, measurement result also compares with 0 month sample result of the test, and result of the test sees Table 4:
Table 4 accelerated test result
Three, long term test:
Get this product by commercially available back, place 20 ℃ ± 2 ℃, relative humidity RH60% ± 10% time to place 12 months, test respectively at sampling in 0,3,6,9,12 month, measurement result also compares with 0 month sample result of the test, and result of the test sees Table 5:
Table 5 long-term test results
The specific embodiment
Embodiment 1
Fat-soluble vitamin for injection prescription (1000):
Vitamin A palmitate 1.5g
Vitamin D
23g
Vitamin E 7g
Vitamin K
1130g
Tween 80 40g
Polysorbas20 0.5g
Ethanol 250ml
Glycine 2g
Cysteine hydrochloride 0.3g
Sodium sulfite 2g
EDTA-2Na 0.3g
Mannitol 40g
Fat-soluble vitamin for injection technology:
(1) take by weighing 0.3g EDTA-2Na and add in 75% water for injection (25 ℃ of water temperatures), be stirred to whole dissolvings, and inflated with nitrogen carries out saturatedly, obtain solution A, standby;
(2) take by weighing 40g mannitol, 2g glycine, 0.3g cysteine hydrochloride, 2g sodium sulfite and join in the solution A, be stirred to whole dissolvings, regulating pH is 5.0, adds 250ml ethanol, stirs, and obtains solution B, standby;
(3) take by weighing the 3g vitamin D
2, put in the beaker, add 1ml ethanol, make dissolving, obtain solution C, standby;
(4) take by weighing 7g successively and give birth to plain E, 40g Tween 80,0.5g polysorbas20,130g vitamin K
1, the 1.5g vitamin A palmitate, put in the beaker, stir and made dissolving in 8 minutes, add in the solution C,, to same beaker, continue to stir and made dissolving in 30 minutes with 1ml alcohol gradation cleaning solution C beaker, obtain solution D, standby;
(5) solution B, solution D are slowly poured in the agitator tank, constantly stir simultaneously, and water is rinsed well beaker, after the dissolving, regulate pH value to 6 with the NaOH solution of 0.1mol/L fully, benefit adds to the full amount of water for injection, add 0.05% (g/ml) active carbon, stirring at room 20 minutes, coarse filtration is taken off charcoal; Survey pH value and intermediate content, carry out aseptic filter pressing after qualified;
(6) liquid medicine filling: indoor hundred grades of clean packing, micropore filter by 0.22 μ m to the aseptic filtration of medicinal liquid twin-stage after, be delivered to the numerical control liquid-filling machine, carry out liquid medicine filling according to the medicinal liquid loading amount, and carry out automatic false add plug, then semi-finished product are put on the clean freeze drying box internal partition, from top to bottom put successively, the products temperature gauge head is placed in required thermometric position on request, shuts chamber door then, medicinal liquid is carried out lyophilization;
(7) lyophilizing: medicine is put into case before the freeze dryer, closes chamber door, drive cold before case, when products temperature being reduced to-40 ℃, be incubated 2 hours, begin cold rear cabinet, when the rear cabinet temperature was chilled to below-45 ℃, the beginning evacuation when vacuum arrives 8Pa, began intensification.Begin to heat up from-40 ℃, the plate temperature heats up with the per 30 minutes speed with 5 ℃ below-25 ℃ the time; Insulation is 1 hour when arriving-20 ℃; Insulation is 2 hours when arriving-15 ℃; Insulation is 2 hours when arriving-10 ℃; Insulation is 2 hours when arriving-5 ℃; Insulation is 1 hour when arriving 0 ℃, observes goods watermark disappearance situation later on, progressively heats up, and products temperature arrives 20 ℃, is incubated 6 hours;
(8) fill nitrogen: lyophilization finishes, and connects the nitrogen pipeline through 0.22 μ m filter aseptic filtration, fills nitrogen.For the first time being filled to vacuum (probably needs 5-6MPa) when 650mbar, when being evacuated to the 10Pa left and right sides again, be filled to vacuum when 950mbar for the second time; Filling finish in cold dried case, carry out automatic tamponade under the condition of partial vacuum after, open charging valve and inflate, inflation is opened chamber door after finishing, and takes out the temperature of articles gauge head, from bottom to top presses the opposite order outlet of inlet.
Embodiment 2
Fat-soluble vitamin for injection prescription (1000):
Vitamin A palmitate 2.5g
Vitamin D
28g
Vitamin E 10g
Vitamin K
1180g
Tween 80 60g
Polysorbas20 1.5g
Ethanol 400ml
Glycine 3g
Cysteine hydrochloride 0.8g
Sodium sulfite 4g
EDTA-2Na 0.8g
Mannitol 60g
Fat-soluble vitamin for injection technology:
(1) take by weighing 0.8g EDTA-2Na and add in 90% water for injection (25 ℃ of water temperatures), be stirred to whole dissolvings, and inflated with nitrogen carries out saturatedly, obtain solution A, standby;
(2) take by weighing 60g mannitol, 3g glycine, 0.8g cysteine hydrochloride, 4g sodium bisulfate and join in the solution A, be stirred to whole dissolvings, regulating pH is 7.0, adds 400ml ethanol, stirs, and obtains solution B, standby;
(3) take by weighing the 8g vitamin D
2, put in the beaker, add 4ml ethanol, make dissolving, obtain solution C, standby;
(4) take by weighing 10g vitamin E, 60g Tween 80,1.5g polysorbas20,180g vitamin K successively
1, the 2.5g vitamin A palmitate, put in the beaker, stir and made dissolving in 12 minutes, add in the solution C,, to same beaker, continue to stir and made dissolving in 50 minutes with 5ml ethanol gradation cleaning solution C beaker, obtain solution D, standby;
(5) solution B, solution D are slowly poured in the agitator tank, constantly stir simultaneously, and water is rinsed well beaker, after the dissolving, regulate pH value to 7 with the HCL solution of 0.1mol/L fully, benefit adds to the full amount of water for injection, add 0.05% (g/ml) active carbon, stirring at room 40 minutes, coarse filtration is taken off charcoal; Survey pH value and intermediate content, carry out aseptic filter pressing after qualified;
(6) liquid medicine filling: indoor hundred grades of clean packing, micropore filter by 0.22 μ m to the aseptic filtration of medicinal liquid twin-stage after, be delivered to the numerical control liquid-filling machine, carry out liquid medicine filling according to the medicinal liquid loading amount, and carry out automatic false add plug, then semi-finished product are put on the clean freeze drying box internal partition, from top to bottom put successively, the products temperature gauge head is placed in required thermometric position on request, shuts chamber door then, medicinal liquid is carried out lyophilization;
(7) lyophilizing: medicine is put into case before the freeze dryer, closes chamber door, drive cold before case, when products temperature being reduced to-40 ℃, be incubated 2 hours, begin cold rear cabinet, when the rear cabinet temperature was chilled to below-45 ℃, the beginning evacuation when vacuum arrives 10Pa, began intensification.Begin to heat up from-40 ℃, the plate temperature heats up with the per 30 minutes speed with 5 ℃ below-25 ℃ the time; Insulation is 1 hour when arriving-20 ℃; Insulation is 2 hours when arriving-15 ℃; Insulation is 2 hours when arriving-10 ℃; Insulation is 2 hours when arriving-5 ℃; Insulation is 1 hour when arriving 0 ℃, observes goods watermark disappearance situation later on, progressively heats up, and products temperature arrives 20 ℃, is incubated 6 hours;
(8) fill nitrogen: lyophilization finishes, and connects the nitrogen pipeline through 0.22 μ m filter aseptic filtration, fills nitrogen.For the first time being filled to vacuum (probably needs 5-6MPa) when 650mbar, when being evacuated to the 10Pa left and right sides again, be filled to vacuum when 950mbar for the second time; Filling finish in cold dried case, carry out automatic tamponade under the condition of partial vacuum after, open charging valve and inflate, inflation is opened chamber door after finishing, and takes out the temperature of articles gauge head, from bottom to top presses the opposite order outlet of inlet.
Embodiment 3
Fat-soluble vitamin for injection prescription (1000):
Vitamin A palmitate 2g
Vitamin D
25g
Vitamin E 9g
Vitamin K
1150g
Tween 80 50g
Polysorbas20 1g
Ethanol 300ml
Glycine 2.5g
Cysteine hydrochloride 0.5g
Sodium sulfite 3g
EDTA-2Na 0.5g
Mannitol 50g
Fat-soluble vitamin for injection technology:
(1) take by weighing 0.5g EDTA-2Na and add in 85% water for injection (25 ℃ of water temperatures), be stirred to whole dissolvings, and inflated with nitrogen carries out saturatedly, obtain solution A, standby;
(2) take by weighing 50g mannitol, 2.5g glycine, 0.5g cysteine hydrochloride, 3g sodium sulfite and join in the solution A, be stirred to whole dissolvings, regulating pH is 6.0, adds 300ml ethanol, stirs, and obtains solution B, standby;
(3) take by weighing the 5g vitamin D
2, put in the beaker, add 4ml ethanol, make dissolving, obtain solution C, standby;
(4) take by weighing 9g vitamin E, 50g Tween 80,1g polysorbas20,150g vitamin K successively
1, the 2g vitamin A palmitate, put in the beaker, stir and made dissolving in 10 minutes, add in the solution C,, to same beaker, continue to stir and made dissolving in 45 minutes with 3ml ethanol gradation cleaning solution C beaker, obtain solution D, standby;
(5) slowly pour into solution B, solution D in the agitator tank, constantly stir simultaneously, and water is rinsed beaker well, fully after the dissolving, NaOH solution with 0.1mol/L is regulated pH value to 6.5, and benefit adds to the full amount of water for injection, and adds 0.05% (g/ml) active carbon, stirring at room 35 minutes, coarse filtration is taken off charcoal; Survey pH value and intermediate content, carry out aseptic filter pressing after qualified;
(6) liquid medicine filling: indoor hundred grades of clean packing, micropore filter by 0.22 μ m to the aseptic filtration of medicinal liquid twin-stage after, be delivered to the numerical control liquid-filling machine, carry out liquid medicine filling according to the medicinal liquid loading amount, and carry out automatic false add plug, then semi-finished product are put on the clean freeze drying box internal partition, from top to bottom put successively, the products temperature gauge head is placed in required thermometric position on request, shuts chamber door then, medicinal liquid is carried out lyophilization;
(7) lyophilizing: medicine is put into case before the freeze dryer, closes chamber door, drive cold before case, when products temperature being reduced to-40 ℃, be incubated 2 hours, begin cold rear cabinet, when the rear cabinet temperature was chilled to below-45 ℃, the beginning evacuation when vacuum arrives 9Pa, began intensification.Begin to heat up from-40 ℃, the plate temperature heats up with the per 30 minutes speed with 5 ℃ below-25 ℃ the time; Insulation is 1 hour when arriving-20 ℃; Insulation is 2 hours when arriving-15 ℃; Insulation is 2 hours when arriving-10 ℃; Insulation is 2 hours when arriving-5 ℃; Insulation is 1 hour when arriving 0 ℃, observes goods watermark disappearance situation later on, progressively heats up, and products temperature arrives 20 ℃, is incubated 6 hours;
(8) fill nitrogen: lyophilization finishes, and connects the nitrogen pipeline through 0.22 μ m filter aseptic filtration, fills nitrogen.For the first time being filled to vacuum (probably needs 5-6MPa) when 650mbar, when being evacuated to the 10Pa left and right sides again, be filled to vacuum when 950mbar for the second time; Filling finish in cold dried case, carry out automatic tamponade under the condition of partial vacuum after, open charging valve and inflate, inflation is opened chamber door after finishing, and takes out the temperature of articles gauge head, from bottom to top presses the opposite order outlet of inlet.
Embodiment 4
Fat-soluble vitamin for injection prescription (1000):
Vitamin A palmitate 1.94g
Vitamin D
25mg
Vitamin E 9.1g
Vitamin K
1150mg
Tween 80 50g
Polysorbas20 0.875g
Ethanol 300ml
Glycine 2.5g
Cysteine hydrochloride 0.5g
Sodium sulfite 2.5g
EDTA-2Na 0.5g
Mannitol 50g
Fat-soluble vitamin for injection technology:
(1) EDTA-2Na that takes by weighing 0.5g adds in 80% water for injection (25 ℃ of water temperatures), is stirred to whole dissolvings, and inflated with nitrogen carries out saturatedly, obtains solution A, and is standby;
(2) take by weighing 50g mannitol, 2.5g glycine, 0.5g cysteine hydrochloride, 2.5g sodium sulfite and join in the solution A, be stirred to whole dissolvings, regulating pH is 6.0, adds 300ml ethanol, stirs, and obtains solution B, standby;
(3) take by weighing the 5mg vitamin D
2, put in the beaker, add 2ml ethanol, make dissolving, obtain solution C, standby;
(4) take by weighing 9.1g vitamin E, 50g Tween 80,0.875g polysorbas20,150mg vitamin K successively
1, the 1.94g vitamin A palmitate, put in the beaker, stir and made dissolving in 10 minutes, join in the solution C,, to same beaker, continue to stir and made dissolving in 40 minutes with 2ml ethanol gradation cleaning solution C beaker, obtain solution D, standby;
(5) with solution B, the solution of solution D is slowly poured in the agitator tank, constantly stir simultaneously, and water rinses beaker well, after the dissolving, regulates pH value 6.4 with the NaOH solution of 0.1mol/L fully, benefit adds to the full amount of water for injection, add 0.05% (g/ml) active carbon, stirring at room 30 minutes, coarse filtration is taken off charcoal; Survey pH value and intermediate content, carry out aseptic filter pressing after qualified;
(6) liquid medicine filling: indoor hundred grades of clean packing, micropore filter by 0.22 μ m to the aseptic filtration of medicinal liquid twin-stage after, be delivered to the numerical control liquid-filling machine, carry out liquid medicine filling according to the medicinal liquid loading amount, and carry out automatic false add plug, then semi-finished product are put on the clean freeze drying box internal partition, from top to bottom put successively, the products temperature gauge head is placed in required thermometric position on request, shuts chamber door then, medicinal liquid is carried out lyophilization;
(7) lyophilizing: medicine is put into case before the freeze dryer, closes chamber door, drive cold before case, when products temperature being reduced to-40 ℃, be incubated 2 hours, begin cold rear cabinet, when the rear cabinet temperature was chilled to below-45 ℃, the beginning evacuation when vacuum arrives 8Pa, began intensification.Begin to heat up from-40 ℃, the plate temperature heats up with the per 30 minutes speed with 5 ℃ below-25 ℃ the time; Insulation is 1 hour when arriving-20 ℃; Insulation is 2 hours when arriving-15 ℃; Insulation is 2 hours when arriving-10 ℃; Insulation is 2 hours when arriving-5 ℃; Insulation is 1 hour when arriving 0 ℃, observes goods watermark disappearance situation later on, progressively heats up, and products temperature arrives 20 ℃, is incubated 6 hours;
(8) fill nitrogen: lyophilization finishes, and connects the nitrogen pipeline through 0.22 μ m filter aseptic filtration, fills nitrogen.For the first time being filled to vacuum (probably needs 5-6MPa) when 650mbar, when being evacuated to the 10Pa left and right sides again, be filled to vacuum when 950mbar for the second time; Filling finish in cold dried case, carry out automatic tamponade under the condition of partial vacuum after, open charging valve and inflate, inflation is opened chamber door after finishing, and takes out the temperature of articles gauge head, from bottom to top presses the opposite order outlet of inlet, promptly gets fat-soluble vitamin for injection.
Embodiment 5
Fat-soluble vitamin for injection prescription (1500):
Vitamin A palmitate 2.91g
Vitamin D
27.5mg
Vitamin E 13.65g
Vitamin K
1225mg
Tween 80 75g
Polysorbas20 1.3125g
Ethanol 450ml
Glycine 3.75g
Cysteine hydrochloride 0.75g
Sodium sulfite 3.75g
EDTA-2Na 0.75g
Mannitol 75g
Fat-soluble vitamin for injection technology:
(1) EDTA-2Na that takes by weighing 0.75g adds in 80% water for injection (25 ℃ of water temperatures), is stirred to whole dissolvings, and inflated with nitrogen carries out saturatedly, obtains solution A, and is standby;
(2) mannitol, 3.75g glycine, 0.75g cysteine hydrochloride, the 3.75g sodium sulfite that takes by weighing 75g joins in the solution A, is stirred to whole dissolvings, and regulating pH is 6.0, adds 450ml ethanol, stirs, and obtains solution B, and be standby;
(3) take by weighing the 7.5mg vitamin D
2, put in the beaker, add 2ml ethanol, make dissolving, obtain solution C, standby;
(4) take by weighing 13.65g vitamin E, 75g Tween 80,1.3125g polysorbas20,225mg vitamin K successively
1, the 2.91g vitamin A palmitate, put in the beaker, stir and made dissolving in 10 minutes, join in the solution C,, to same beaker, continue to stir and made dissolving in 40 minutes with 2ml ethanol gradation cleaning solution C beaker, obtain solution D, standby;
(5) slowly pour into solution B, solution D in the agitator tank, constantly stir simultaneously, and water is rinsed beaker well, fully after the dissolving, regulate pH value 6.4 with the NaOH solution of 0.1mol/L, benefit adds to the full amount of water for injection, and adds 0.05% (g/ml) active carbon, stirring at room 30 minutes, coarse filtration is taken off charcoal; Survey pH value and intermediate content, carry out aseptic filter pressing after qualified;
(6) liquid medicine filling: indoor hundred grades of clean packing, micropore filter by 0.22 μ m to the aseptic filtration of medicinal liquid twin-stage after, be delivered to the numerical control liquid-filling machine, carry out liquid medicine filling according to the medicinal liquid loading amount, and carry out automatic false add plug, then semi-finished product are put on the clean freeze drying box internal partition, from top to bottom put successively, the products temperature gauge head is placed in required thermometric position on request, shuts chamber door then, medicinal liquid is carried out lyophilization;
(7) lyophilizing: medicine is put into case before the freeze dryer, closes chamber door, drive cold before case, when products temperature being reduced to-40 ℃, be incubated 2 hours, begin cold rear cabinet, when the rear cabinet temperature was chilled to below-45 ℃, the beginning evacuation when vacuum arrives 10Pa, began intensification.Begin to heat up from-40 ℃, the plate temperature heats up with the per 30 minutes speed with 5 ℃ below-25 ℃ the time; Insulation is 1 hour when arriving-20 ℃; Insulation is 2 hours when arriving-15 ℃; Insulation is 2 hours when arriving-10 ℃; Insulation is 2 hours when arriving-5 ℃; Insulation is 1 hour when arriving 0 ℃, observes goods watermark disappearance situation later on, progressively heats up, and products temperature arrives 20 ℃, is incubated 6 hours;
(8) fill nitrogen: lyophilization finishes, and connects the nitrogen pipeline through 0.22 μ m filter aseptic filtration, fills nitrogen.For the first time being filled to vacuum (probably needs 5-6MPa) when 650mbar, when being evacuated to the 10Pa left and right sides again, be filled to vacuum when 950mbar for the second time; Filling finish in cold dried case, carry out automatic tamponade under the condition of partial vacuum after, open charging valve and inflate, inflation is opened chamber door after finishing, and takes out the temperature of articles gauge head, from bottom to top presses the opposite order outlet of inlet, promptly gets fat-soluble vitamin for injection.
Claims (6)
1. fat-soluble vitamin for injection, the prescription that it is characterized in that this fat-soluble vitamin for injection are formed:
Vitamin A palmitate 1.5-2.5 weight portion
Vitamin D
2The 3-8 weight portion
Vitamin E 7-10 weight portion
Vitamin K
1The 130-180 weight portion
Tween 80 40-60 weight portion
Polysorbas20 0.5-1.5 weight portion
Ethanol 250-400 weight portion
Glycine 2-3 weight portion
Cysteine hydrochloride 0.3-0.8 weight portion
Sodium sulfite 2-4 weight portion
EDTA-2Na 0.3-0.8 weight portion
Mannitol 40-60 weight portion.
2. a kind of fat-soluble vitamin for injection according to claim 1 is characterized in that the prescription composition of this fat-soluble vitamin for injection is by weight ratio:
Vitamin A palmitate 1.5g
Vitamin D
23g
Vitamin E 7g
Vitamin K
1130g
Tween 80 40g
Polysorbas20 0.5g
Ethanol 250ml
Glycine 2g
Cysteine hydrochloride 0.3g
Sodium sulfite 2g
EDTA-2Na 0.3g
Mannitol 40g.
3. a kind of fat-soluble vitamin for injection according to claim 1 is characterized in that the prescription composition of this fat-soluble vitamin for injection is by weight ratio:
Vitamin A palmitate 2.5g
Vitamin D
28g
Vitamin E 10g
Vitamin K
1180g
Tween 80 60g
Polysorbas20 1.5g
Ethanol 400ml
Glycine 3g
Cysteine hydrochloride 0.8g
Sodium sulfite 4g
EDTA-2Na 0.8g
Mannitol 60g.
4. a kind of fat-soluble vitamin for injection according to claim 1 is characterized in that the prescription composition of this fat-soluble vitamin for injection is by weight ratio:
Vitamin A palmitate 2g
Vitamin D
25g
Vitamin E 9g
Vitamin K
1150g
Tween 80 50g
Polysorbas20 1g
Ethanol 300ml
Glycine 2.5g
Cysteine hydrochloride 0.5g
Sodium sulfite 3g
EDTA-2Na 0.5g
Mannitol 50g.
5. the preparation method of each described fat-soluble vitamin for injection among the claim 1-4 is characterized in that this preparation method comprises the steps:
(1) to add the 75-90% water temperature be in 25 ℃ the water for injection, to be stirred to whole dissolvings to the EDTA-2Na that takes by weighing recipe quantity, and inflated with nitrogen carries out saturatedly, obtains solution A, standby;
(2) mannitol, glycine, cysteine hydrochloride, the sodium sulfite that takes by weighing recipe quantity joins in the solution A, is stirred to whole dissolvings, and adjusting pH is 5.0-7.0, adds recipe quantity ethanol, stirs, and obtains solution B, and be standby;
(3) take by weighing the recipe quantity vitamin D
2, put in the beaker, add 1-4ml ethanol, make dissolving, obtain solution C, standby;
(4) take by weighing recipe quantity vitamin E, Tween 80, polysorbas20, vitamin K successively
1, vitamin A palmitate, put in the beaker, stir and made dissolving in 8-12 minute, add in the solution C,, to same beaker, continue to stir and made dissolving in 30-50 minute with 1-5ml ethanol gradation cleaning solution C beaker, obtain solution D, standby;
(5) slowly pour into solution B, solution D in the agitator tank, constantly stir simultaneously, and water is rinsed beaker well, fully after the dissolving, regulate pH value between 6-7 with the NaOH solution of 0.1mol/L or the HCL solution of 0.1mol/L, benefit adds to the full amount of water for injection, and adds the 0.05%g/ml active carbon, stirring at room 20-40 minute, coarse filtration was taken off charcoal; Survey pH value and intermediate content, carry out aseptic filter pressing after qualified;
(6) liquid medicine filling: indoor hundred grades of clean packing, micropore filter by 0.22 μ m to the aseptic filtration of medicinal liquid twin-stage after, be delivered to the numerical control liquid-filling machine, carry out liquid medicine filling according to the medicinal liquid loading amount, and carry out automatic false add plug, then semi-finished product are put on the clean freeze drying box internal partition, from top to bottom put successively, the products temperature gauge head is placed in required thermometric position on request, shuts chamber door then, medicinal liquid is carried out lyophilization;
(7) lyophilizing: medicine is put into case before the freeze dryer, close chamber door, the cold preceding case of driving is when reducing to products temperature-40 ℃, be incubated 2 hours, begin cold rear cabinet, when the rear cabinet temperature is chilled to below-45 ℃, the beginning evacuation, when vacuum arrives 8～10Pa, begin to heat up, begin to heat up from-40 ℃, the plate temperature heats up with the per 30 minutes speed with 5 ℃ below-25 ℃ the time; Insulation is 1 hour when arriving-20 ℃; Insulation is 2 hours when arriving-15 ℃; Insulation is 2 hours when arriving-10 ℃; Insulation is 2 hours when arriving-5 ℃; Insulation is 1 hour when arriving 0 ℃, observes goods watermark disappearance situation later on, progressively heats up, and products temperature arrives 20 ℃, is incubated 6 hours;
(8) fill nitrogen: lyophilization finishes, and connects the nitrogen pipeline through 0.22 μ m filter aseptic filtration, fills nitrogen, is filled to vacuum at 650mbar for the first time; Be evacuated to about 10Pa again; For the second time be filled to vacuum at 950mbar; Filling finish in cold dried case, carry out automatic tamponade under the condition of partial vacuum after, open charging valve and inflate, inflation is opened chamber door after finishing, and takes out the temperature of articles gauge head, from bottom to top presses the opposite order outlet of inlet.
6. the preparation method of the described fat-soluble vitamin for injection of claim 5 is characterized in that what this preparation method was all carried out under the lucifuge operation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008102230464A CN101366712B (en) | 2008-09-26 | 2008-09-26 | Method for preparing fat-soluble vitamin for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008102230464A CN101366712B (en) | 2008-09-26 | 2008-09-26 | Method for preparing fat-soluble vitamin for injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101366712A CN101366712A (en) | 2009-02-18 |
| CN101366712B true CN101366712B (en) | 2011-07-27 |
Family
ID=40410804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008102230464A Active CN101366712B (en) | 2008-09-26 | 2008-09-26 | Method for preparing fat-soluble vitamin for injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101366712B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940557B (en) * | 2009-07-10 | 2011-12-07 | 华北制药集团制剂有限公司 | Method for preparing fat-soluble vitamin freeze-dried powder injection |
| CN102429864B (en) * | 2011-11-29 | 2013-03-06 | 海南灵康制药有限公司 | Medicinal compound of fat-soluble vitamin injection (II) and water-soluble vitamin for injection and preparation method thereof |
| CN102525959B (en) * | 2012-01-13 | 2013-12-18 | 海南良方医药有限公司 | Fat-soluble vitamin composition for injection and preparation method thereof |
| CN105663144A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin water-based preparation for animals and preparing method and use method thereof |
| CN105663145A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin injection liquid for animals and preparing method and use method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1561970A (en) * | 2004-04-12 | 2005-01-12 | 沈阳药科大学 | Fat soluble vitamin freeze-drying emulsion and its preparing method |
| CN1843327A (en) * | 2006-04-17 | 2006-10-11 | 重庆医药工业研究院有限责任公司 | Stable freeze-dried formulation containing multiple kinds of vitamin and its preparation method |
| CN1923207A (en) * | 2005-09-02 | 2007-03-07 | 信谊药厂 | Compound recipe vitamin freeze-dried powder for injection and its preparing process |
| CN101129388A (en) * | 2007-08-15 | 2008-02-27 | 四川科伦药业股份有限公司 | Pharmaceutical composition of compound fat-soluble vitamin and method of preparing the same |
-
2008
- 2008-09-26 CN CN2008102230464A patent/CN101366712B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1561970A (en) * | 2004-04-12 | 2005-01-12 | 沈阳药科大学 | Fat soluble vitamin freeze-drying emulsion and its preparing method |
| CN1923207A (en) * | 2005-09-02 | 2007-03-07 | 信谊药厂 | Compound recipe vitamin freeze-dried powder for injection and its preparing process |
| CN1843327A (en) * | 2006-04-17 | 2006-10-11 | 重庆医药工业研究院有限责任公司 | Stable freeze-dried formulation containing multiple kinds of vitamin and its preparation method |
| CN101129388A (en) * | 2007-08-15 | 2008-02-27 | 四川科伦药业股份有限公司 | Pharmaceutical composition of compound fat-soluble vitamin and method of preparing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101366712A (en) | 2009-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101366712B (en) | Method for preparing fat-soluble vitamin for injection | |
| RU2420210C2 (en) | High-caloric nutritive supplement | |
| Serna-Thomé et al. | Use of functional foods and oral supplements as adjuvants in cancer treatment | |
| US11957652B2 (en) | Compositions comprising citrulline and leucine and their use in the treatment of diabetes and metabolic syndrome | |
| EP3377071B1 (en) | Human milk oligosaccharides for treating antibiotic associated complications | |
| RU2744580C2 (en) | Compositions containing sialylated oligosaccharides for use in infants or young children to prevent obesity in later life or related comorbidities and to promote normal growth | |
| US11541067B2 (en) | HMO compositions and methods for reducing detrimental proteolytic metabolites | |
| CN111683665A (en) | Human milk oligosaccharides for microbiota regulation and synthetic compositions thereof | |
| TWI337066B (en) | Dietary supplement | |
| CN106605744A (en) | Composition capable of reducing fat, slimming, expelling toxin and beautifying, as well as preparation method thereof | |
| CN100503634C (en) | T4 synthetic product and application thereof | |
| EP3212198B1 (en) | Synthetic composition and method for promoting mucosal healing | |
| CN106798755B (en) | Probiotic composition with function of conditioning hyperplasia of mammary glands and application thereof | |
| WO2018103729A1 (en) | Use of chlorogenic acid in preparation of drugs or health-care products for stimulating appetite | |
| KR20210107035A (en) | Compositions and methods for promoting intestinal wall healing | |
| CN110446532A (en) | Treatment method relevant to stomach and intestine implantation material | |
| CN115997920A (en) | Total nutrient medical use formula food for wounded patients | |
| CN102512437A (en) | Medicinal composition of liposoluble vitamin injection (I) and water-soluble vitamin for injection and preparation method thereof | |
| CN101693014B (en) | Process for preparing coenzyme A medicament freeze drying preparation | |
| CN101683356A (en) | Water-soluble vitamin preparation for injection and preparation method thereof | |
| CN102018720B (en) | Preparation method of vitamin complex freeze-dried powder injection | |
| ITRM20130655A1 (en) | PRODUCT BASED ON AN ASSOCIATION OF GLUCOMANNAN AND INOSITLE | |
| CN107050039A (en) | Oral protective effect and its application of the crocin to Ischemia Reperfusion Brain Injury | |
| JPS59199634A (en) | Novel composition containing protein fractions based on three kinds of minipeptides available for dietetics, convalescence and therapy and use thereof | |
| CN102871971A (en) | Freeze-dried powder injection of vitamin B6 and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: XI'AN DETIAN PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: DOCTOR ANTE TECHNOLOGY DEVELOPMENT CO., LTD. Effective date: 20130201 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 100070 FENGTAI, BEIJING TO: 710119 XI'AN, SHAANXI PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20130201 Address after: 710119 No. 9, innovation road, new industrial park, Xi'an hi tech Industrial Development Zone, Shaanxi, Xi'an Patentee after: Xi'an Detian Pharmaceutical Co., Ltd. Address before: 100070, No. 10, No., Spark Road, Fengtai District Science Park, Beijing, China. 3 Patentee before: Beijing Boshi Antai Technology Co., Ltd. |
|
| C56 | Change in the name or address of the patentee | ||
| CP03 | Change of name, title or address |
Address after: 710119 No. 9, innovation road, new industrial park, Xi'an hi tech Industrial Development Zone, Shaanxi Patentee after: Xi'an Yuanda Detian pharmaceutical Limited by Share Ltd Address before: 710119 No. 9, innovation road, new industrial park, Xi'an hi tech Industrial Development Zone, Shaanxi, Xi'an Patentee before: Xi'an Detian Pharmaceutical Co., Ltd. |