CN102525959A - Fat-soluble vitamin composition for injection and preparation method thereof - Google Patents
Fat-soluble vitamin composition for injection and preparation method thereof Download PDFInfo
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- CN102525959A CN102525959A CN2012100108784A CN201210010878A CN102525959A CN 102525959 A CN102525959 A CN 102525959A CN 2012100108784 A CN2012100108784 A CN 2012100108784A CN 201210010878 A CN201210010878 A CN 201210010878A CN 102525959 A CN102525959 A CN 102525959A
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- 229940088594 vitamin Drugs 0.000 title claims abstract description 49
- 229930003231 vitamin Natural products 0.000 title claims abstract description 49
- 235000013343 vitamin Nutrition 0.000 title claims abstract description 49
- 239000011782 vitamin Substances 0.000 title claims abstract description 49
- 150000003722 vitamin derivatives Chemical class 0.000 title claims abstract description 48
- 238000002347 injection Methods 0.000 title claims abstract description 41
- 239000007924 injection Substances 0.000 title claims abstract description 41
- 239000000203 mixture Substances 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 36
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims abstract description 34
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 claims abstract description 34
- 239000008215 water for injection Substances 0.000 claims abstract description 29
- VYGQUTWHTHXGQB-UHFFFAOYSA-N Retinol hexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229930003427 Vitamin E Natural products 0.000 claims abstract description 17
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims abstract description 17
- 235000019172 retinyl palmitate Nutrition 0.000 claims abstract description 17
- 229940108325 retinyl palmitate Drugs 0.000 claims abstract description 17
- 239000011769 retinyl palmitate Substances 0.000 claims abstract description 17
- 239000011709 vitamin E Substances 0.000 claims abstract description 17
- 235000019165 vitamin E Nutrition 0.000 claims abstract description 17
- 229940046009 vitamin E Drugs 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims description 78
- 238000003756 stirring Methods 0.000 claims description 38
- 238000005303 weighing Methods 0.000 claims description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000004108 freeze drying Methods 0.000 claims description 14
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 11
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 229930003316 Vitamin D Natural products 0.000 claims description 8
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 8
- 229930003448 Vitamin K Natural products 0.000 claims description 8
- 235000019166 vitamin D Nutrition 0.000 claims description 8
- 239000011710 vitamin D Substances 0.000 claims description 8
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 8
- 235000019168 vitamin K Nutrition 0.000 claims description 8
- 239000011712 vitamin K Substances 0.000 claims description 8
- 150000003721 vitamin K derivatives Chemical class 0.000 claims description 8
- 229940046008 vitamin d Drugs 0.000 claims description 8
- 229940046010 vitamin k Drugs 0.000 claims description 8
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 claims description 7
- 241000143437 Aciculosporium take Species 0.000 claims description 7
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 7
- 229930195725 Mannitol Natural products 0.000 claims description 7
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 7
- 229910052782 aluminium Inorganic materials 0.000 claims description 7
- 239000004411 aluminium Substances 0.000 claims description 7
- 239000000594 mannitol Substances 0.000 claims description 7
- 235000010355 mannitol Nutrition 0.000 claims description 7
- 238000012856 packing Methods 0.000 claims description 7
- 238000012859 sterile filling Methods 0.000 claims description 7
- 239000003643 water by type Substances 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 5
- 238000007689 inspection Methods 0.000 claims description 4
- -1 stir to clarify Substances 0.000 claims 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 abstract description 9
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 abstract description 3
- 229960002061 ergocalciferol Drugs 0.000 abstract description 3
- 235000001892 vitamin D2 Nutrition 0.000 abstract description 3
- 239000011653 vitamin D2 Substances 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 description 16
- 238000004090 dissolution Methods 0.000 description 7
- 239000011772 phylloquinone Substances 0.000 description 7
- 230000007774 longterm Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
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- 230000006378 damage Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229950008882 polysorbate Drugs 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- ABSPRNADVQNDOU-UHFFFAOYSA-N Menaquinone 1 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(C)C(=O)C2=C1 ABSPRNADVQNDOU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
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- 210000004369 blood Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002390 cell membrane structure Anatomy 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940090044 injection Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000008558 metabolic pathway by substance Effects 0.000 description 1
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- 150000002894 organic compounds Chemical class 0.000 description 1
- 235000019175 phylloquinone Nutrition 0.000 description 1
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 description 1
- MBWXNTAXLNYFJB-LKUDQCMESA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-LKUDQCMESA-N 0.000 description 1
- 229960001898 phytomenadione Drugs 0.000 description 1
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- 230000001105 regulatory effect Effects 0.000 description 1
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- 210000002966 serum Anatomy 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940068088 vitamin k 1 Drugs 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a fat-soluble vitamin composition for injection and a preparation method thereof. The major components of the fat-soluble vitamin composition for injection include vitamin A palmitate, vitamin D2, vitamin E and vitamin k1. The major components are dissolved by a special method and then mixed with water for injection at an appropriate temperature, and the mixture is stirred to disperse and dissolve. The clarity and content stability of the sample are further guaranteed to make the quality of the sample more stable and controllable.
Description
Technical field
The present invention relates to a kind of injection freeze-dried powder composition and method of making the same, particularly a kind of fat-soluble vitamin for injection composition and method of making the same.
Background technology
Vitamin is to keep the necessary one type of nutrient of humans and animals body health, and these article are low-molecular-weight organic compound.The daily requirement amount of vitamin is few (often in milligram or microgram) very; They are neither constitute the raw material of body tissue; The material of energy supply in neither body; Yet regulating substance metabolism, promoting growth promoter and keep aspect such as physiological function and but bringing into play important effect, if certain vitamin of long-term lacking will cause disease.
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.After human body received big wound, serum vitamin A, E content significantly descended in the blood, are lower than normal value, and simple diet is taken in the requirement that can not satisfy vitamin under the stress state.Vitimin supplement A can the epithelial function of enhances human body, infects significant to control; Vitamin E has many physiological functions; It all has powerful antioxidation in vivo and in vitro; Can make unsaturated fatty acid on the biological cell membrane structure avoid the attack of free radical; The structure of complete, the stabilate film of protection cell membrane simultaneously, also protects life macromolecule material (DNA) to exempt from the destruction that free radical is attacked.
Fatsoluble vitamin is subject to the destruction of temperature, moisture, illumination, so fat-soluble vitamin for injection the problem that content descends occurs through regular meeting in put procedure.In order to guarantee clinical drug safety, the stability that improves fat-soluble vitamin for injection is the problem that needs solution.
Summary of the invention
The objective of the invention is to disclose a kind of fat-soluble vitamin for injection compositions; Another purpose of the present invention is to disclose the method for preparing of this fat-soluble vitamin for injection freeze-dried powder.
Fat-soluble vitamin for injection composition material of the present invention consists of:
Fatsoluble vitamin composition material composition of the present invention is preferably:
Fat-soluble vitamin for injection composition material composition of the present invention is preferably:
During the raw material of above-mentioned fat-soluble vitamin for injection is formed, add injection water to 3000 parts by volume, said weight portion and parts by volume relation are g/ml.
Fat-soluble vitamin for injection preparation of compositions method of the present invention comprises the steps:
A. take by weighing the vitamin K of formula ratio
1Add in the polyoxyethylene sorbitan monoleate, stirring and dissolving gets solution A;
B. take by weighing the vitamin D of formula ratio
2Join in the solution A, stirring and dissolving gets solution B;
C. the vitamin E that takes by weighing formula ratio joins in the solution B, and stirring and dissolving gets solution C;
D. the vitamin A palmitate that takes by weighing formula ratio joins in the solution C, and stirring and dissolving adds the water for injection that 500-2000 parts by volume temperature is, stirs to clarify; Get solution D
E. formula ratio mannitol is dissolved in 30 ℃ of-40 ℃ of waters for injection of 500-1000 parts by volume, is stirred to dissolving, add 0.05% (g/ml) needle-use activated carbon, stirred 15 minutes under the room temperature, coarse filtration gets solution E;
F. with solution D and solution E mix homogeneously, regulate pH value to 7.5～9.0, add water for injection to 3000 parts by volume with the 0.1mol/L sodium hydroxide solution; Aseptic filtration, sterile filling is in cillin bottle after the intermediate passed examination, and every bottled amount is 3 parts by volume; Press half plug, place the freeze drying box lyophilization, tamponade, lock aluminium lid; The qualified back of full inspection packing gets the fat-soluble vitamin for injection compositions.
The preferred following steps of fat-soluble vitamin for injection preparation of compositions method of the present invention:
A. take by weighing the vitamin K of formula ratio
1Add in the polyoxyethylene sorbitan monoleate, stirring and dissolving gets solution A;
B. take by weighing the vitamin D of formula ratio
2Join in the solution A, stirring and dissolving gets solution B;
C. the vitamin E that takes by weighing formula ratio joins in the solution B, and stirring and dissolving gets solution C;
D. the vitamin A palmitate that takes by weighing formula ratio joins in the solution C, and stirring and dissolving adds the water for injection that 1000 parts by volume temperature are, stirs to clarify, and gets solution D;
E. formula ratio mannitol is dissolved in 30 ℃ of-40 ℃ of waters for injection of 1000 parts by volume, is stirred to dissolving, add 0.05% (g/ml) needle-use activated carbon, stirred 15 minutes under the room temperature, coarse filtration gets solution E;
F. with solution D and solution E mix homogeneously, regulate pH value to 7.8～8.3, add water for injection to 3000 parts by volume with the 0.1mol/L sodium hydroxide solution; Aseptic filtration, sterile filling is in cillin bottle after the intermediate passed examination, and every bottled amount is 3 parts by volume; Press half plug, place the freeze drying box lyophilization, tamponade, lock aluminium lid; The qualified back of full inspection packing gets the fat-soluble vitamin for injection compositions.
The invention provides a kind of composition and method of making the same.After the principal agent vitamin A palmitate of fat-soluble vitamin for injection, vitamin D2, vitamin E, vitamin k 1 are pressed the ad hoc approach dissolving among the present invention; The water for injection dispersed with stirring dissolving that adds preference temperature again; Further guarantee the clarity of sample and the stability of content, make the more stable quality of sample controlled.
Experimental example 1 fatsoluble vitamin dissolution studies
Comprise in the fat-soluble vitamin for injection compositions: vitamin A palmitate, vitamin D2, vitamin E, vitamin K1; These four kinds of materials are all water insoluble; Need be dissolved in earlier in the polyoxyethylene sorbitan monoleate, redispersion is in water, because the good solubilization of polyoxyethylene sorbitan monoleate; Dispersing and dissolving forms settled solution in water.Experimental example is investigated the situation in the whole course of dissolution.See table.
Table one
| Form 1 | Form 2 | Form 3 | |
| Vitamin A palmitate | 1.885g | 1.885g | 1.885g |
| Vitamin D 2 | 0.005g | 0.005g | 0.005g |
| Vitamin E | 9.1g | 9.1g | 9.1g |
| Vitamin K 1 | 0.15g | 0.15g | 0.15g |
| Polyoxyethylene sorbitan monoleate | 50g | 50g | 50g |
| Water for injection | 100ml | 300ml | 500ml |
| The water for injection dilution | To 3000ml | To 3000ml | To 3000ml |
Vitamin A palmitate, vitamin D
2, vitamin E, vitamin K
1Add in the polyoxyethylene sorbitan monoleate, mix homogeneously according to the water for injection stirring of about 30 ℃ of design addings, is observed the state in the course of dissolution, and record dissolves the time completely, and observes the clarity of each solution at this moment, and the result sees table two.
Table two
Experimental example shows vitamin A palmitate, vitamin D
2, vitamin E, vitamin K
1It is after 80s that these four kinds of fatsoluble vitamiies are dissolved in Polysorbate, adds the water for injection dissolving, and the amount of water for injection should be beneficial to dispersing and dissolving like this more than or equal to 1/6 of total amount.
Experimental example 2 fatsoluble vitamin solution temperature researchs
Experimental example is investigated vitamin A palmitate, vitamin D
2, vitamin E, vitamin K
1These four kinds of material dissolutions are in polyoxyethylene sorbitan monoleate, and redispersion is in water, and water temperature is to the influence of dissolution velocity and clarity.
Compositions is formed as follows:
The water for injection temperature is set at: 5 ℃, 10 ℃, 20 ℃, 40 ℃, 50 ℃, 60 ℃.
Vitamin A palmitate, vitamin E, vitamin D
2, vitamin K
1In the adding polyoxyethylene sorbitan monoleate, mix homogeneously, the water for injection 500ml of adding design temperature stirs, and observes the state in the course of dissolution, and record dissolves the time completely, the clarity after the adding of observation water for injection full dose.
The result sees table three:
Because the content of fatsoluble vitamin is responsive to temperature, in conjunction with the result of experimental example 2, we think vitamin A palmitate, vitamin D
2, vitamin E, vitamin K
1It is after 80s that these four kinds of fatsoluble vitamiies are dissolved in Polysorbate, adds the water for injection dissolving, and the temperature of water for injection should be at 20 ℃～40 ℃.
Experimental example 3 fat-soluble vitamin for injection principal agent addition sequences are to the influence of stability
Compositions is formed as follows:
Technology is seen table four
The finished product that above-mentioned three technologies are made carries out the long term test study on the stability: the sample lot number of technology one is 090601; The sample lot number of technology two is 090602; The sample lot number of technology three is 090603;
Experimental condition: put under the condition of 2 ℃-10 ℃ of temperature and preserve, timing sampling is measured each item index,
The result sees table five
Table five
The fat-soluble vitamin for injection long-term test results
Fat-soluble vitamin for injection long term test assay (%) result (090601 technology one)
Fat-soluble vitamin for injection long term test assay (%) result (090602 batch of technology two)
Fat-soluble vitamin for injection long term test assay (%) result (090603 batch of technology three)
Can know that by The above results the sample that technology one and technology two make is 2 ℃-10 ℃ condition held after 24 months, vitamin A palmitate, vitamin D
2Can descend about 6-8% with the content of vitamin K, and each main constituent content of the sample that technology three makes does not have significant change, and clarity obviously is superior to the sample of two other technology.It is thus clear that the sample of technology three is than the more stable quality of the sample of technology one and technology two, controlled.
Following embodiment all can prove the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1: fat-soluble vitamin freeze-dried powder needle of the present invention
A. take by weighing the vitamin K of formula ratio
1Add in the polyoxyethylene sorbitan monoleate, stirring and dissolving gets solution A;
B. take by weighing the vitamin D of formula ratio
2Join in the solution A, stirring and dissolving gets solution B;
C. the vitamin E that takes by weighing formula ratio joins in the solution B, and stirring and dissolving gets solution C;
D. the vitamin A palmitate that takes by weighing formula ratio joins in the solution C, and stirring and dissolving adds the water for injection that 1000 parts by volume temperature are, stirs to clarify, and gets solution D;
E. mannitol is dissolved in 30 ℃ of-40 ℃ of waters for injection of 1000 parts by volume, is stirred to dissolving; Add the solution D mix homogeneously, add the nearly full dose of water for injection, measure the solution pH value, use the 0.1mol/L sodium hydroxide solution to regulate pH value to 7.8-8.2; Add water for injection to 3000 parts by volume, aseptic filtration, sterile filling is in cillin bottle after the intermediate passed examination; Every bottled amount is 3 parts by volume, presses half plug, places the freeze drying box lyophilization; Tamponade, lock aluminium lid are examined qualified back packing entirely, get the fat-soluble vitamin for injection compositions.
Embodiment 2: fat-soluble vitamin freeze-dried powder needle of the present invention
A. take by weighing the vitamin K of formula ratio
1Add in the polyoxyethylene sorbitan monoleate, stirring and dissolving gets solution A;
B. take by weighing the vitamin D of formula ratio
2Join in the solution A, stirring and dissolving gets solution B;
C. the vitamin E that takes by weighing formula ratio joins in the solution B, and stirring and dissolving gets solution C;
D. the vitamin A palmitate that takes by weighing formula ratio joins in the solution C, and stirring and dissolving adds the water for injection that 1000 parts by volume temperature are, stirs to clarify, and gets solution D;
E. mannitol is dissolved in 30 ℃ of-40 ℃ of waters for injection of 1000 parts by volume, is stirred to dissolving; Add the solution D mix homogeneously, add the nearly full dose of water for injection, measure the solution pH value, use the 0.1mol/L sodium hydroxide solution to regulate pH value to 7.8-8.2; Add water for injection to 3000 parts by volume, aseptic filtration, sterile filling is in cillin bottle after the intermediate passed examination; Every bottled amount is 3 parts by volume, presses half plug, places the freeze drying box lyophilization; Tamponade, lock aluminium lid are examined qualified back packing entirely, get the fat-soluble vitamin for injection compositions.
Embodiment 3: fat-soluble vitamin freeze-dried powder needle of the present invention
A. take by weighing the vitamin K of formula ratio
1Add in the polyoxyethylene sorbitan monoleate, stirring and dissolving gets solution A;
B. take by weighing the vitamin D of formula ratio
2Join in the solution A, stirring and dissolving gets solution B;
C. the vitamin E that takes by weighing formula ratio joins in the solution B, and stirring and dissolving gets solution C;
D. the vitamin A palmitate that takes by weighing formula ratio joins in the solution C, and stirring and dissolving adds the water for injection that 1000 parts by volume temperature are, stirs to clarify, and gets solution D;
E. mannitol is dissolved in 30 ℃ of-40 ℃ of waters for injection of 1000 parts by volume, is stirred to dissolving; Add the solution D mix homogeneously, add the nearly full dose of water for injection, measure the solution pH value, use the 0.1mol/L sodium hydroxide solution to regulate pH value to 7.8-8.2; Add water for injection to 3000 parts by volume, aseptic filtration, sterile filling is in cillin bottle after the intermediate passed examination; Every bottled amount is 3 parts by volume, presses half plug, places the freeze drying box lyophilization; Tamponade, lock aluminium lid are examined qualified back packing entirely, get the fat-soluble vitamin for injection compositions.
Claims (4)
1. one kind prepares the fat-soluble vitamin for injection method for compositions, it is characterized in that this method comprises the steps:
A. take by weighing the vitamin K of formula ratio
1Add in the polyoxyethylene sorbitan monoleate, stirring and dissolving gets solution A;
B. take by weighing the vitamin D of formula ratio
2Join in the solution A, stirring and dissolving gets solution B;
C. the vitamin E that takes by weighing formula ratio joins in the solution B, and stirring and dissolving gets solution C;
D. the vitamin A palmitate that takes by weighing formula ratio joins in the solution C, stirring and dissolving, and adding 500-2000 parts by volume temperature is 20 ℃-40 ℃ a water for injection, stirs to clarify, and gets solution D;
E. mannitol is dissolved in 20 ℃ of-40 ℃ of waters for injection of 500-1000 parts by volume, is stirred to dissolving, add 0.05% (g/ml) needle-use activated carbon, stirred 15 minutes under the room temperature, coarse filtration gets solution E,
F. with solution D and solution E mix homogeneously, regulate pH value to 7.5～9.0, add water for injection to the 2000-3000 parts by volume with the 0.1mol/L sodium hydroxide solution; Aseptic filtration, sterile filling is in cillin bottle after the intermediate passed examination, and every bottled amount is 3 parts by volume; Press half plug, place the freeze drying box lyophilization, tamponade, lock aluminium lid; The qualified back of full inspection packing gets the fat-soluble vitamin for injection compositions, and the raw material of said composition consists of:
2. fat-soluble vitamin for injection compositions as claimed in claim 1 is characterized in that the said composition raw material consists of:
3. fat-soluble vitamin for injection compositions as claimed in claim 1 is characterized in that the said composition raw material consists of:
4. like the arbitrary described fat-soluble vitamin for injection preparation of compositions method of claim 1-3, it is characterized in that the method for preparing of said composition comprises the steps:
A. take by weighing the vitamin K of formula ratio
1Add in the polyoxyethylene sorbitan monoleate, stirring and dissolving gets solution A;
B. take by weighing the vitamin D of formula ratio
2Join in the solution A, stirring and dissolving gets solution B;
C. the vitamin E that takes by weighing formula ratio joins in the solution B, and stirring and dissolving gets solution C;
D. the vitamin A palmitate that takes by weighing formula ratio joins in the solution C, and stirring and dissolving adds 1000 parts by volume temperature and be 30 ℃-40 ℃ water for injection, stir to clarify, solution D;
E. formula ratio mannitol is dissolved in 30 ℃ of-40 ℃ of waters for injection of 1000 parts by volume, is stirred to dissolving, add 0.05% (g/ml) needle-use activated carbon, stirred 15 minutes under the room temperature, coarse filtration gets solution E;
F. with solution D and solution E mix homogeneously, regulate pH value to 7.8～8.3, add water for injection to 3000 parts by volume with the 0.1mol/L sodium hydroxide solution; Aseptic filtration, sterile filling is in cillin bottle after the intermediate passed examination, and every bottled amount is 3 parts by volume; Press half plug, place the freeze drying box lyophilization, tamponade, lock aluminium lid; The qualified back of full inspection packing gets the fat-soluble vitamin for injection compositions.
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| CN1903207A (en) * | 2005-07-29 | 2007-01-31 | 青岛众智医药科技有限公司 | Fat-soluble vitamin freeze-dried prepn. and its prepn. 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 |
| CN101366712A (en) * | 2008-09-26 | 2009-02-18 | 北京博时安泰科技发展有限公司 | Method for preparing fat-soluble vitamin for injection |
| CN101606939A (en) * | 2009-07-27 | 2009-12-23 | 徐新盛 | A kind of fat-soluble vitamin freeze-dried powder needle and preparation method thereof |
| CN101632679A (en) * | 2009-04-20 | 2010-01-27 | 邓盛齐 | Composite vitamin for injection and preparation method thereof |
| CN101940557A (en) * | 2009-07-10 | 2011-01-12 | 华北制药集团制剂有限公司 | Method for preparing fat-soluble vitamin freeze-dried powder injection |
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| CN1923207A (en) * | 2005-09-02 | 2007-03-07 | 信谊药厂 | Compound recipe vitamin freeze-dried powder for injection and its preparing process |
| CN101366712A (en) * | 2008-09-26 | 2009-02-18 | 北京博时安泰科技发展有限公司 | Method for preparing fat-soluble vitamin for injection |
| CN101632679A (en) * | 2009-04-20 | 2010-01-27 | 邓盛齐 | Composite vitamin for injection and preparation method thereof |
| CN101940557A (en) * | 2009-07-10 | 2011-01-12 | 华北制药集团制剂有限公司 | Method for preparing fat-soluble vitamin freeze-dried powder injection |
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