CN1689564A - Vitamin C composition containing sodium vitamin C - Google Patents
Vitamin C composition containing sodium vitamin C Download PDFInfo
- Publication number
- CN1689564A CN1689564A CN 200410033951 CN200410033951A CN1689564A CN 1689564 A CN1689564 A CN 1689564A CN 200410033951 CN200410033951 CN 200410033951 CN 200410033951 A CN200410033951 A CN 200410033951A CN 1689564 A CN1689564 A CN 1689564A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- sodium ascorbate
- powder injection
- preparation
- injectable sterile
- 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.)
- Granted
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims abstract description 240
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 title claims abstract description 116
- 229930003268 Vitamin C Natural products 0.000 title claims abstract description 116
- 235000019154 vitamin C Nutrition 0.000 title claims abstract description 116
- 239000011718 vitamin C Substances 0.000 title claims abstract description 116
- 239000000203 mixture Substances 0.000 title claims abstract description 55
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 title 1
- 229910052708 sodium Inorganic materials 0.000 title 1
- 239000011734 sodium Substances 0.000 title 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims abstract description 75
- 238000002347 injection Methods 0.000 claims abstract description 45
- 239000007924 injection Substances 0.000 claims abstract description 45
- 239000000843 powder Substances 0.000 claims abstract description 36
- 239000003814 drug Substances 0.000 claims abstract description 12
- 229960005055 sodium ascorbate Drugs 0.000 claims description 73
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 73
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 73
- 238000002360 preparation method Methods 0.000 claims description 40
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 31
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 238000004806 packaging method and process Methods 0.000 claims description 2
- 238000012856 packing Methods 0.000 description 39
- 239000007788 liquid Substances 0.000 description 37
- 239000007789 gas Substances 0.000 description 32
- 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 description 24
- 239000002131 composite material Substances 0.000 description 23
- 229910052782 aluminium Inorganic materials 0.000 description 20
- 239000000284 extract Substances 0.000 description 17
- 239000000523 sample Substances 0.000 description 16
- 238000000034 method Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 238000003756 stirring Methods 0.000 description 9
- 239000008215 water for injection Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960005070 ascorbic acid Drugs 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- 238000009413 insulation Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 229960000935 dehydrated alcohol Drugs 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000004531 microgranule Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 230000037354 amino acid metabolism Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000009529 body temperature measurement Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011082 depyrogenation Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003701 histiocyte Anatomy 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- XKLJHFLUAHKGGU-UHFFFAOYSA-N nitrous amide Chemical compound ON=N XKLJHFLUAHKGGU-UHFFFAOYSA-N 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000013441 quality evaluation Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003700 vitamin C derivatives Chemical class 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The bacteria-free powder composition for injection contains vitamin C sodium, vitamin C and optional alkaline regulator in the total amount of 0-15 wt%. The composition has obviously improved medicine safety.
Description
Technical field
The present invention relates to a kind of safe vitamin C aseptic powder injection that contains sodium ascorbate solid composite and preparation method thereof.In particular, the present invention relates to a kind of vitamin C aseptic powder injection solid composite that contains sodium ascorbate, the amount of the gas that said composition may command vitamin c powder pin aseptic when dissolving produces and air pressure in the clinical use in acceptable safety range.
Background technology
Vitamin C participates in the synthetic of matter between synthetic, the collagen protein of amino acid metabolism, neurotransmitter and histiocyte, can reduce the permeability of blood capillary, solidifying of accelerate blood, stimulate coagulation function, promote that ferrum absorbs at enteral, impel rate and blood-lipid decreased, increase resistance infecting, participate in function of detoxification, and the effect that antfhistamine effect is arranged and stop carcinogen (nitrosamine) to generate.
Vitamin C is used widely at present clinically, and wherein a large amount of patients' life has been saved in the use of vitamin C injection in critical patient's parenterai administration especially.But there is a well-known shortcoming in vitamin C injection, i.e. vitamin C quality instability under aqueous solution state, easy variable color and content decline.
The good stability of injection Vitamin C preparation (as injection powder pin) in put procedure that exists with solid form is in injection solution.Vitamin C is acid strong, and its solution pH value is about 2.16, because the injection pH value generally is controlled at (" pharmaceutics " the 4th edition in 4～9 scopes, the People's Health Publisher, 2000:233), when being prepared into injection form medicine, pH value must be heightened could medication in the suitable scope.Vitamin C is more stable in acid solution in addition, in alkaline solution, be easy to oxidation deactivation (" new pharmacology " the 15th edition, the People's Health Publisher, 2003:630), so pH value should not be higher than 7.0.For Cevalin, more suitably scope comprises that the pH value that refers to injection by 2000 editions two ones of Chinese Pharmacopoeias or American Pharmacopeia 25 editions is 5.0-7.0, is 4.5-7.0 by the pH value of CNS injection vitamin c powder pin.Therefore for the vitamin C that solid form is existed can reach rational pH value when clinical dilution is used, adopt usually and in solid vitamin C powder, adding a certain amount of alkaline conditioner.
Because sodium hydroxide alkalescence is too strong, in the processes such as fill of pharmaceutical production, sodium hydroxide powder injures producers and infringement equipment easily, and its alkalescence is too strong, cause the medicine instability easily, alkaline conditioner therefore commonly used at present is carbonate pharmaceutically commonly used basically.
The injection vitamin c powder pin that occurs on the market all is at present to adopt the direct aseptic subpackaged mode at cillin bottle of different raw materials is produced basically.Production method as conventional in the market injection vitamin c powder pin is: in the ratio of every 1g vitamin C adding 0.25g natrium carbonicum calcinatum, in the airtight cillin bottle of according to dosage packing into after respectively several different raw materials being mixed.
Though but make moderate progress than injection by ascorbic stability in the preparation that adds powdered sodium carbonate, but bring serious dosing difficulty and potential safety hazard simultaneously: before the medication of commercially available injection vitamin c powder pin, medical personnel need be dissolved this solid preparation in airtight cillin bottle.In course of dissolution, produce a large amount of CO in the bottle
2Gas is because the effect of immense pressure (contains the 1g vitamin C and the 0.25g natrium carbonicum calcinatum is an example, the CO of generation with the every 10ml bottle of regular size in the bottle
2Gas is about 52ml, also promptly increases by 5.2 atmospheric pressure in bottle at least), medical personnel directly extract medicinal liquid and wash open because of syringe piston often and fail, or medicinal liquid sprays syringe and causes damage and cause dosage inaccurate under reaction force acts when extracting syringe needle.Use sodium bicarbonate can produce more gas and pressure as alkaline conditioner.
Producing problem that excess air causes medical personnel's medication difficulty during dilution can't solve since the nineteen ninety-five launch always.Attempting with the way that extracts medicinal liquid after the empty needle head venting again is to violate aseptic injection safe medication principle and harmful to patient health: since the suction function medicinal liquid when extracting can by with atmosphere that the empty needle head communicates in pollutions such as antibacterial, microgranule, moreover increase cillin bottle plug puncture time and can make that microgranule increases in the medicinal liquid.
Therefore still need to seek the ascorbic preparation of a kind of better injection at present, it should satisfy the characteristics safe and convenient to use of vitamin C stable in properties, preparation in the storage put procedure simultaneously.
Summary of the invention
By experimental study relatively, we provide a kind of vitamin C pharmaceutical preparation of brand-new composition.After in this vitamin C pharmaceutical preparation, adding sodium ascorbate, we are surprisingly found out that, contain sodium ascorbate and vitamin C at the same time and low content/or the solid composite of alkali-free regulator in, vitamin C thereby provides a kind of safer and more effective injection Vitamin C preparation when can keeping good stability and can not produce huge air pressure.
The application provides a kind of Injectable sterile powder injection composition on the one hand, wherein contain sodium ascorbate and vitamin C, sodium ascorbate and ascorbic weight ratio are 99.8-0.2: 0.2-99.8, the optional alkaline conditioner that contains in the compositions, wherein the content of alkaline conditioner is calculated as 0-15% with sodium ascorbate, vitamin C and the alkaline conditioner weight sum that exists in the compositions, and described Injectable sterile powder injection composition uses the pH value of solvent for injection dissolving back solution to be 4-7.Sodium ascorbate and ascorbic weight ratio are 50-99.8: 0.2-50 preferably in the compositions, are more preferably 80-90: 10-20.
When not containing material such as sodium carbonate or sodium bicarbonate in the compositions, Cevalin does not produce gas when dissolving, and pH value is also in safety range simultaneously.Therefore can avoid using in the preparation any alkaline conditioner fully by adding sodium ascorbate.
One of ordinary skill in the art can add the part alkaline conditioner by method of the present invention in preparation on the other hand, and alkaline conditioner is preferably sodium carbonate or sodium bicarbonate.Wherein the content of alkaline conditioner calculates with the sodium ascorbate, vitamin C and the alkaline conditioner weight sum that exist in the compositions and is not higher than 15%, and preferred content is not higher than 10%.Be higher than 15% alkaline conditioner and cause producing in the solution excessive gas, inconvenient clinical use, this is that the present invention will avoid.In the certain content scope by alkaline conditioner, control preparation neutral and alkali regulator, sodium ascorbate and ascorbic ratio, the pH value that can reach the solution after the dilution simultaneously is still in safety range, and the Cevalin dissolving time produces a small amount of gas, and producing micro-pressure, to make medical personnel extract medicinal liquid on the contrary more convenient.The preparation that sodium ascorbate and small amount of carbonate be provided in the time of of the present invention providing has been avoided in the existing preparation when containing the excess carbon hydrochlorate and cause being clinical use because of producing the problem that excessive gas is inconvenient to use.
Using sodium ascorbate is surprising as an important component of the preparation among the present invention, because in the preparation of injection, does not also make the precedent of Vitamin C preparation pH regulator agent with sodium ascorbate.
The theory that one of ordinary skill in the art propose according to the present invention, can realize the present invention by the ratio of vitamin C, sodium ascorbate, natrium carbonicum calcinatum, sodium bicarbonate in any means adjusting preparation of this area, and can in preparation, add other adjuvant component according to the general knowledge of this area, as the acceptable adjuvant commonly used of human bodies such as sodium chloride.
Concrete the application provides a kind of Injectable sterile powder injection composition, wherein sodium ascorbate: vitamin C: the weight ratio 10-99.5 of natrium carbonicum calcinatum: 0.5-80.5: 0-10.5, preferred 30-90: 0.5-60.5: 0-10.5.
One of ordinary skill in the art can prepare compositions of the present invention according to the known common technology means of this area.The invention provides two kinds of methods that prepare the Injectable sterile powder injection composition: (1) said composition can obtain in container by each component raw material in the pharmaceutical preparation is mixed the back direct packaging, concrete one of ordinary skill in the art can be with each component sterile solid crushing screening, abundant mix homogeneously, according to dosage aseptic subpackaged in aseptic clean powder pin usefulness bottle, tamponade, gland are promptly; The sterilizing room relative humidity preferably is adjusted in 50% or lower on demand.(2) said composition also can be passed through after each component raw material dissolving in the pharmaceutical preparation, be filled to and carry out lyophilization in the container, concrete one of ordinary skill in the art can be with after mixed dissolution, depyrogenation and the aseptic filtration in each component water, carries out bottle lyophilizing (or after the deep bid lyophilizing aseptic subpackaged making).
The invention provides the Injectable sterile powder injection composition on the other hand and be used for preventing or treating the application of the medicine of disease in production, described medicine is used for the patient that needs injection vitamin C treats to be used.
Vitamin C, sodium ascorbate, natrium carbonicum calcinatum and sodium bicarbonate related among the present invention can conveniently be buied the pharmaceutical grade product from the market, can use after common method aseptic process such as aseptic recrystallization.Can be as sodium ascorbate with reference to the aseptic recrystallization of CN1116202A.Aseptic sodium ascorbate also can be made by vitamin C and inorganic or organic sodium salt salify post crystallization or lyophilizing in aqueous solution, water-mixed alkoxide solution.Should avoid illumination, oxidation destruction and metal ion pollution in sodium ascorbate and the vitamin C processing procedure.Vitamin C, 60 ℃ of drying under reduced pressure weightlessness of sodium ascorbate preferably are controlled at and are not more than 1%, are not more than 0.25% better.
Aseptic reagent used in the present invention can obtain by the whole bag of tricks well known to those skilled in the art, below describes for example:
Aseptic sodium ascorbate: under the nitrogen protection; room temperature adds 89g vitamin C, 26.8g natrium carbonicum calcinatum stirring and dissolving in the 200ml water for injection; be warmed up to 50 ℃ and add 0.3g active carbon stirring 15min, carbon removal is filtered in insulation, filters through the insulation of 0.22 μ m sterile filters again.A small amount of water for injection filter wash layer filters with method.Under the aseptic condition, add aseptic dehydrated alcohol 400ml under filtrate is stirred, be refrigerated to-5～-10 ℃ of crystallizations, filter, a small amount of aseptic cold absolute ethanol washing is collected 40 ℃ of vacuum dryings of crystallization to constant weight, gets the aseptic sodium ascorbate of 76g white.
Aseptic vitamin C: 110ml water for injection is heated to 80 ℃, under the nitrogen protection, adds 100g vitamin C stirring and dissolving, adds the 0.3g active carbon again and stirs 15min, and carbon removal is filtered in insulation, filters through the insulation of 0.22 μ m sterile filters again.Under the aseptic condition, filtrate stirring is refrigerated to 0～-5 ℃ of crystallization, filters, and a small amount of aseptic cold absolute ethanol washing is collected 40 ℃ of vacuum dryings of crystallization to constant weight, gets the aseptic vitamin C of 62.1g white.
Aseptic natrium carbonicum calcinatum: under the nitrogen protection, the 250g natrium carbonicum calcinatum is dissolved in the 700mL90 ℃ of water for injection, and stirring and dissolving adds the 0.75g active carbon again and stirs 15min, filters carbon removal, filters through 0.22 μ m sterile filters again.Under the aseptic condition, filtrate stirring drips the 3.5L dehydrated alcohol after being chilled to room temperature, drips back stirring at room crystallization, filters, and uses absolute ethanol washing, is dried to constant weight in about 300 ℃, gets the aseptic natrium carbonicum calcinatum of 195g white.
Description of drawings
Fig. 1, working sample produce the device of gas flow
The following examples are incited somebody to action more detailed explanation the present invention, but are not that the present invention is construed as limiting.
Embodiment
PH value is measured, formulation content is measured and undertaken by China national drug standard WS-10001-(HD-0070) 2002 methods.
PH value is measured: with tested goods powder 0.5g, after the cold water 10ml dissolving of newly boiling, (2000 editions two appendix IX B of Chinese Pharmacopoeia) measure its pH value in accordance with the law.
Gas production is measured: produce the volume of gas when adopting discharge opeing eudiometry indoor temperature measurement sample with solvent dilution, determine the volume of gas according to the volume of the liquid of discharging.Tested goods remove moulds lid, slowly adds the dissolving of 5ml water for injection with syringe under the room temperature, by syringe needle gas in the bottle is drawn the conduit that is connected to Fig. 1 device and measures gas production.The volume of the liquid that the volume of gas equals to discharge deducts the water for injection volume.The liquid of surveying the auxiliary usefulness of volume can be with inert fluids such as dehydrated alcohol or lightweight silicone oil.
The colour measurement of solution: get an amount of thin up of goods powder and become every 1ml to be equivalent to contain the solution of vitamin C 50mg,, measure trap at the wavelength place of 420nm according to spectrophotography (2000 editions two appendix IV A of Chinese Pharmacopoeia).
Goods dissolving and extraction medicinal liquid: in being equivalent to the ascorbic goods of 1g, inject 5ml water for injection rapidly and extract syringe needle, rock dissolving.Medicinal liquid extracts with the 10ml syringe.
The sample preparation
The comparative example 1
Get 100g vitamin C, the abundant mix homogeneously of 39.6g sodium bicarbonate of crossing 60 mesh sieves respectively.Every bottle of packing 1.40g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of sodium bicarbonate is 71.6: 28.4.
The comparative example 2
Get the sodium ascorbate of crossing 60 mesh sieves respectively, every bottle of packing 1.12g (quite 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.
Embodiment 1
Get 99.5g sodium ascorbate, the abundant mix homogeneously of 0.5g vitamin C of crossing 120 mesh sieves respectively.Every bottle of packing 1.12g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 99.5: 0.5.
Embodiment 2
Get 99g sodium ascorbate, the abundant mix homogeneously of 1g vitamin C of crossing 120 mesh sieves respectively.Every bottle of packing 1.12g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 99: 1.
Embodiment 3
Get 98.2g sodium ascorbate, the abundant mix homogeneously of 1.8g vitamin C of crossing 120 mesh sieves respectively.Every bottle of packing 1.12g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 98.2: 1.8.
Embodiment 4
Get 95.7g sodium ascorbate, the abundant mix homogeneously of 4.3g vitamin C of crossing 120 mesh sieves respectively.Every bottle of packing 1.12g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 95.7: 4.3.
Embodiment 5
Get 88g sodium ascorbate, the abundant mix homogeneously of 12g vitamin C of crossing 60 mesh sieves respectively.Every bottle of packing 1.11g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 88: 12.
Embodiment 6
Get 84.7g sodium ascorbate, the abundant mix homogeneously of 15.3g vitamin C of crossing 60 mesh sieves respectively.Every bottle of packing 1.10g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 84.7: 15.3.
Embodiment 7
Get 78.6g sodium ascorbate, the abundant mix homogeneously of 21.4g vitamin C of crossing 60 mesh sieves respectively.Every bottle of packing 1.10g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 78.6: 21.4.
Embodiment 8
Get 71.4g sodium ascorbate, the abundant mix homogeneously of 28.6g vitamin C of crossing 60 mesh sieves respectively.Every bottle of packing 1.09g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 71.4: 28.6.
Embodiment 9
Get 50g sodium ascorbate, the abundant mix homogeneously of 50g vitamin C of crossing 60 mesh sieves respectively.Every bottle of packing 1.06g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Containing sodium ascorbate and ascorbic weight ratio in the Vitamin C preparation is 50: 50.
Embodiment 10
Get 70.1g sodium ascorbate, 41.9g vitamin C, the abundant mix homogeneously of natrium carbonicum calcinatum 6.3g of crossing 60 mesh sieves respectively.Every bottle of packing 1.14g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The weight ratio that contains sodium ascorbate, vitamin C and natrium carbonicum calcinatum in the Vitamin C preparation is 59.3: 35.4: 5.3.
Embodiment 11
Get 74.3g sodium ascorbate, 34g vitamin C, the abundant mix homogeneously of natrium carbonicum calcinatum 10.2g of crossing 60 mesh sieves respectively.Every bottle of packing 1.19g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The weight ratio that contains sodium ascorbate, vitamin C and natrium carbonicum calcinatum in the Vitamin C preparation is 62.7: 28.7: 8.6.
Embodiment 12
Get 31.4g sodium ascorbate, 64.1g vitamin C, the abundant mix homogeneously of natrium carbonicum calcinatum 10.7g of crossing 60 mesh sieves respectively.Every bottle of packing 1.15g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The weight ratio that contains sodium ascorbate, vitamin C and natrium carbonicum calcinatum in the Vitamin C preparation is 29.6: 60.3: 10.1.
Embodiment 13
Get 10g sodium ascorbate, 85.5g vitamin C, the abundant mix homogeneously of natrium carbonicum calcinatum 10.7g of crossing 60 mesh sieves respectively.Every bottle of packing 1.12g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The weight ratio that contains sodium ascorbate, vitamin C and natrium carbonicum calcinatum in the Vitamin C preparation is 9.4: 80.5: 10.1.
Embodiment 14
Get 90g sodium ascorbate, 8g vitamin C, the abundant mix homogeneously of natrium carbonicum calcinatum 2g of crossing 120 mesh sieves respectively.Every bottle of packing 1.14g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The weight ratio that contains sodium ascorbate, vitamin C and natrium carbonicum calcinatum in the Vitamin C preparation is 90: 8: 2.
Embodiment 15
Get sodium ascorbate 70.1g, vitamin C 41.9g, the abundant mix homogeneously of sodium bicarbonate 9.9g of crossing 60 mesh sieves respectively.Every bottle of packing 1.17g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The weight ratio that contains vitamin C, sodium ascorbate and sodium bicarbonate in the Vitamin C preparation is 57.5: 34.4: 8.1.
Embodiment 16
Get 70.1g sodium ascorbate, 41.9g vitamin C, natrium carbonicum calcinatum 5.0g, the abundant mix homogeneously of sodium bicarbonate 2.0g of crossing 60 mesh sieves respectively.Every bottle of packing 1.14g (being equivalent to the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The weight ratio that contains vitamin C, sodium ascorbate, natrium carbonicum calcinatum and sodium bicarbonate in the Vitamin C preparation is 58.9: 35.2: 4.2: 1.7.
Embodiment 17
71.4g sodium ascorbate, 28.6g vitamin C (weight ratio is 71.4: 28.6 :) in the dissolving of 700ml water for injection, are added water for injection to 920ml.Every bottle of packing 10ml of 20ml control cillin bottle (being equivalent to contain the 1g vitamin C).Inlet, carry out lyophilization as follows: the plate temperature is provided with-50 ℃, the goods cartonning, temperature to be tasted with discrimination is pulled to below-45 ℃, is incubated 2 hours.The condenser refrigeration is opened vacuum pump to below-60 ℃, and the drying baker evacuation reaches below the 10pa.Heating flaggy control sample temperature is lower than-35 ℃ of frozen portions extremely and disappears, and is warming up to 0 ℃ with 5 ℃/hour, is incubated 2 hours, is warming up to 30 ℃ with 5 ℃/hour again, is incubated 20 hours.Confirm that drying is complete, fill nitrogen, tamponade in the case, air inlet outlet.The plastic-aluminum composite cover rolls mouth.
Embodiment 18
Solution pH value and gas production among more commercially available vitamin C powder injection formulation and the embodiment after the goods dilution the results are shown in Table 1.
Table 1, gas production and pH value are relatively
| Sample | Each components by weight | The solution pH value | Gas production (ml) | |||
| Sodium ascorbate | Vitamin C | Sodium bicarbonate | Sodium carbonate | |||
| Commercially available sample | ????0 | ????80 | ????0 | ????20 | ????4.82 | ????51.9 |
| The comparative example 1 | ????0 | ????71.6 | ????28.4 | ????0 | ????4.84 | ????104 |
| The comparative example 2 | ????100 | ????0 | ????0 | ????0 | ????7.69 | ????0 |
| Embodiment 1 | ????99.5 | ????0.5 | ????0 | ????0 | ????6.47 | ????0 |
| Embodiment 2 | ????99 | ????1 | ????0 | ????0 | ????6.21 | ????0 |
| Embodiment 3 | ????98.2 | ????1.8 | ????0 | ????0 | ????5.97 | ????0 |
| Embodiment 4 | ????95.7 | ????4.3 | ????0 | ????0 | ????5.54 | ????0 |
| Embodiment 5 | ????88 | ????12 | ????0 | ????0 | ????5.01 | ????0 |
| Embodiment 6 | ????84.7 | ????15.3 | ????0 | ????0 | ????4.85 | ????0 |
| Embodiment 7 | ????78.6 | ????21.4 | ????0 | ????0 | ????4.66 | ????0 |
| Embodiment 8 | ????71.4 | ????28.6 | ????0 | ????0 | ????4.52 | ????0 |
| Embodiment 9 | ????50 | ????50 | ????0 | ????0 | ????4.03 | ????0 |
| Embodiment 10 | ????59.3 | ????35.4 | ????0 | ????5.3 | ????4.69 | ????11.2 |
| Embodiment 11 | ????62.7 | ????28.7 | ????0 | ????8.6 | ????5.98 | ????20.1 |
| Embodiment 12 | ????29.6 | ????60.3 | ????0 | ????10.1 | ????4.54 | ????22.7 |
| Embodiment 13 | ????9.4 | ????80.5 | ????0 | ????10.1 | ????4.11 | ????21.9 |
| Embodiment 14 | ????90 | ????8 | ????0 | ????2 | ????5.67 | ????2.6 |
| Embodiment 15 | ????57.5 | ????34.4 | ????8.1 | ????0 | ????4.95 | ????23.9 |
| Embodiment 16 | ????58.9 | ????35.2 | ????1.7 | ????4.2 | ????4.88 | ????14.3 |
| Embodiment 17 (lyophilizing) | ????71.4 | ????28.6 | ????0 | ????0 | ????4.57 | ????0 |
Annotate: contain vitamin C 1g in every bottle of the vitamin C powder injection formulation of commercially available sample, natrium carbonicum calcinatum 0.25g, the molded cillin bottle plastic-aluminum of 10ml composite cover packing.
The powder sample needle gas production that is not contained sodium ascorbate by The above results as can be seen is too high, is inconvenient to use.
Embodiment 19
Goods dissolving and extraction medicinal liquid the results are shown in Table 2 among more commercially available vitamin C powder injection formulation and the embodiment.
Medicinal liquid is extracted relatively in table 2, dissolving back
| Sample | Extract the medicinal liquid operation convenience relatively |
| Commercially available sample | Pressure is excessive during dissolving, has gas to discharge from the pin mouth.Treat to extract medicinal liquid after gas is not discharged, syringe piston is under pressure suddenly and is difficult to control during inserting needle, medicinal liquid ejection easily under reaction force acts when extracting syringe needle. |
| The comparative example 1 | Pressure is excessive during dissolving, has gas to discharge from the pin mouth.Treat to extract medicinal liquid after gas is not discharged, suddenly being under pressure during inserting needle is difficult to control, medicinal liquid ejection easily under reaction force acts when extracting syringe needle. |
| Embodiment 1 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 2 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 3 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 4 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 5 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 6 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 7 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 8 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 9 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 10 | Dissolving hour hands mouth place does not have gas and discharges.Syringe piston is controlled easily.Because intrinsic pressure effect, to extract medicinal liquid more convenient than common mode. |
| Embodiment 11 | Dissolving hour hands mouth place does not have gas and discharges.Syringe piston is controlled easily.Because intrinsic pressure effect, to extract medicinal liquid more convenient than common mode. |
| Embodiment 12 | Dissolving hour hands mouth place does not have gas and discharges.Syringe piston is controlled easily.Because intrinsic pressure effect, to extract medicinal liquid more convenient than common mode. |
| Embodiment 13 | Dissolving hour hands mouth place does not have gas and discharges.Syringe piston is controlled easily.Because intrinsic pressure effect, to extract medicinal liquid more convenient than common mode. |
| Embodiment 14 | Dissolving hour hands mouth place does not have gas and discharges.Syringe piston is controlled easily.Because intrinsic pressure effect, to extract medicinal liquid more convenient than common mode. |
| Embodiment 15 | Dissolving hour hands mouth place does not have gas and discharges.Syringe piston is controlled easily.Because intrinsic pressure effect, to extract medicinal liquid more convenient than common mode. |
| Embodiment 16 | Dissolving hour hands mouth place does not have gas and discharges.Syringe piston is controlled easily.Because intrinsic pressure effect, to extract medicinal liquid more convenient than common mode. |
| Embodiment 17 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 18 | Common mode extracts medicinal liquid, and is convenient |
The powder sample needle that is not contained sodium ascorbate by The above results as can be seen is difficult to extract medicinal liquid, is inconvenient to use.
Embodiment 20
Carry out 60 ℃ of 10 days influence factors by 2000 editions two method requirements of Chinese Pharmacopoeia and test investigation, goods stability the results are shown in Table 3 among more commercially available Vitamin C preparation and the embodiment.
The color of table 3,60 ℃ of 10 days influence factor testing liquiies relatively
| Sample | Trap (420nm) | |
| 0 day sample | 10 days samples | |
| Commercially available sample | ????0.016 | ????0.036 |
| Embodiment 1 | ????0.012 | ????0.013 |
| Embodiment 2 | ????0.012 | ????0.013 |
| Embodiment 3 | ????0.012 | ????0.013 |
| Embodiment 4 | ????0.012 | ????0.013 |
| Embodiment 5 | ????0.012 | ????0.013 |
| Embodiment 6 | ????0.012 | ????0.013 |
| Embodiment 7 | ????0.012 | ????0.013 |
| Embodiment 8 | ????0.012 | ????0.013 |
| Embodiment 9 | ????0.012 | ????0.014 |
The wavelength place trap of 420nm is the important indicator of 2000 editions two vitamin Cs of Chinese Pharmacopoeia and vitamin C injection quality evaluation, and trap greatly then sample quality is bad.
By table 3 result as can be seen, contain sodium ascorbate but the embodiment goods of alkali-free regulator than commercially available vitamin c powder pin better stability of preparation.
Therefore (see The Merck Index, 10ed p1230), adds sodium ascorbate and can reduce ascorbic consumption, and do not influence the ascorbic content of preparation active component after dilution to have identical pharmacological action at equimolar sodium ascorbate and vitamin C.If but use sodium ascorbate to replace vitamin C (comparative example 2) to cause the pH value of the solution after the sample dissolution fully is 7.69, do not meet standard.
Use sodium ascorbate and vitamin C can obviously reduce the gas quantum of output of sample when diluting by uniting, both can satisfy the needs of dilution back pH value of solution, the gas production of may command dilution back solution conveniently uses syringe needle to extract solution in certain scope again.
Among the present invention, " being equivalent to " refers to active component to calculate content with the vitamin C form the same.
Claims (10)
1, a kind of Injectable sterile powder injection composition, wherein contain sodium ascorbate and vitamin C, sodium ascorbate and ascorbic weight ratio are 99.8-0.2: 0.2-99.8, the optional alkaline conditioner that contains in the compositions, wherein the content of alkaline conditioner is calculated as 0-15% with sodium ascorbate, vitamin C and the alkaline conditioner weight sum that exists in the compositions, and described Injectable sterile powder injection composition uses the pH value of solvent for injection dissolving back solution to be 4-7.
2, Injectable sterile powder injection composition as claimed in claim 1, wherein sodium ascorbate and ascorbic weight ratio are 50-99.8: 0.2-50.
3, Injectable sterile powder injection composition as claimed in claim 2, wherein sodium ascorbate and ascorbic weight ratio are 80-90: 10-20.
4, as the described aseptic injection powder injection composition of any claim of claim 1-3, wherein said alkaline conditioner is selected from sodium carbonate, sodium bicarbonate or its mixture.
5, as the described Injectable sterile powder injection composition of any claim of claim 1-3, wherein the content of alkaline conditioner is 0-10.0%.
6, Injectable sterile powder injection composition as claimed in claim 1, wherein sodium ascorbate: vitamin C: the weight ratio 10-99.5 of alkaline conditioner: 0.5-80.5: 0-10.5.
7, Injectable sterile powder injection composition as claimed in claim 6, wherein sodium ascorbate: vitamin C: the weight ratio 30-90.0 of alkaline conditioner: 5-60.5: 0-10.5.
8, the preparation method of the described Injectable sterile powder injection composition of claim 1-7 is characterized in that each component raw material in the pharmaceutical preparation is mixed the back direct packaging in container.
9, the preparation method of the described Injectable sterile powder injection composition of claim 1-7 is characterized in that being filled to and carrying out lyophilization in the container after each component raw material dissolving in the pharmaceutical preparation.
10, the described Injectable sterile powder injection composition of claim 1-7 is used for preventing or treating the application of the medicine of disease in production, and described medicine is used for the patient that needs injection vitamin C treats to be used.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410033951 CN1279904C (en) | 2004-04-21 | 2004-04-21 | Vitamin C composition containing sodium vitamin C |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410033951 CN1279904C (en) | 2004-04-21 | 2004-04-21 | Vitamin C composition containing sodium vitamin C |
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| CN1689564A true CN1689564A (en) | 2005-11-02 |
| CN1279904C CN1279904C (en) | 2006-10-18 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558114A (en) * | 2011-12-28 | 2012-07-11 | 上海新先锋药业有限公司 | Preparation method for vitamin C bulk pharmaceutical |
| CN104490903A (en) * | 2014-12-30 | 2015-04-08 | 王大光 | Compound vitamin injection pharmaceutical composition and preparation method thereof |
| CN104606209A (en) * | 2014-12-30 | 2015-05-13 | 王大光 | Compound vitamin medicine composition for injection and preparation method of compound vitamin medicine composition |
| CN106491531A (en) * | 2017-01-11 | 2017-03-15 | 河北天成药业股份有限公司 | A kind of ascorbic production technology of injection |
| CN109641055A (en) * | 2017-07-20 | 2019-04-16 | 德尔塔菲制药股份有限公司 | Novel anti-malignant tumor agent based on cancer cell metabolism specificity |
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2004
- 2004-04-21 CN CN 200410033951 patent/CN1279904C/en not_active Expired - Lifetime
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558114A (en) * | 2011-12-28 | 2012-07-11 | 上海新先锋药业有限公司 | Preparation method for vitamin C bulk pharmaceutical |
| CN102558114B (en) * | 2011-12-28 | 2015-12-09 | 上海新亚药业有限公司 | A kind of preparation method of vitamin C bulk pharmaceutical |
| CN104490903A (en) * | 2014-12-30 | 2015-04-08 | 王大光 | Compound vitamin injection pharmaceutical composition and preparation method thereof |
| CN104606209A (en) * | 2014-12-30 | 2015-05-13 | 王大光 | Compound vitamin medicine composition for injection and preparation method of compound vitamin medicine composition |
| CN106491531A (en) * | 2017-01-11 | 2017-03-15 | 河北天成药业股份有限公司 | A kind of ascorbic production technology of injection |
| CN106491531B (en) * | 2017-01-11 | 2019-11-26 | 河北天成药业股份有限公司 | A kind of ascorbic production technology of injection |
| CN109641055A (en) * | 2017-07-20 | 2019-04-16 | 德尔塔菲制药股份有限公司 | Novel anti-malignant tumor agent based on cancer cell metabolism specificity |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1279904C (en) | 2006-10-18 |
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