CN1698600A - Vitamin C composition containing amino acids - Google Patents
Vitamin C composition containing amino acids Download PDFInfo
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- CN1698600A CN1698600A CN 200410042549 CN200410042549A CN1698600A CN 1698600 A CN1698600 A CN 1698600A CN 200410042549 CN200410042549 CN 200410042549 CN 200410042549 A CN200410042549 A CN 200410042549A CN 1698600 A CN1698600 A CN 1698600A
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Abstract
The invention provides a vitamin C composition which comprises amino acids and vitamin C. The composition has no use limitation for patients with diseases avoiding sodium salts, and no gas is generated during the germ-free dissolution of the vitamin C powder injection, thus it can be applied safely into clinical uses.
Description
Technical field
The present invention relates to a kind ofly safe contain amino acid whose vitamin C aseptic powder injection with solid composite and preparation method thereof.In particular, the present invention relates to a kind of amino acid whose vitamin C aseptic powder injection solid composite that contains, said composition is avoided sodium salt disease patient to edema or hypertension etc. does not have the restriction of use, and does not produce safety in gas, the clinical use when the aseptic dissolving of vitamin C injection powder pin.
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 Cevalin in critical patient's parenterai administration especially.
But there is well-known shortcoming in Cevalin at present, the one, and vitamin C injection quality instability, variable color and content descend easily; The 2nd, vitamin C injection powder pin dosing dissolving the time produces a large amount of gases, dosing difficulty and serious potential safety hazard is arranged; The 3rd, it is too high that Cevalin contains the sodium salt ratio, causes edema or hypertension etc. to avoid the use of sodium salt disease and be restricted.
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 7.5.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, per diem to refer to the pH value of injection be 5.6-7.4 to the local exchange prescription, 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, add a certain amount of alkaline sodium salt regulator.
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, airtight in the 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 powder injection formulation 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.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.
The applicant provides a kind of and has overcome vitamin c powder the pin compositions of a large amount of aerogenesis problems and the preparation method of said composition in use by adding sodium ascorbate in Chinese patent application 200410033951.5.It is too high that but said composition still exists Cevalin to contain the sodium salt ratio, causes edema or hypertension etc. to avoid the use of sodium salt disease and be restricted.
The pharmaceutically acceptable pH regulator agent commonly used of general this area contains sodium salt basically, so how to seek a kind of suitable pH regulator agent and both can satisfy the safe and convenient to use of vitamin C stable in properties, preparation in the storage put procedure, make again and avoid sodium salt disease patient and also can use the problem that those skilled in the art need solve that is still.
Summary of the invention
By multiple pH regulator agent is compared the stability of Vitamin C preparation and the experimental study of other performance, be surprisingly found out that in the vitamin C pharmaceutical preparation add aminoacid after, vitamin C dosing when can keeping stability does not well produce gas, and avoids sodium salt disease patient and can use yet.Thereby the invention provides a kind of safer and more effective injection Vitamin C preparation, contain aminoacid and vitamin C in the said preparation simultaneously.
Using selected aminoacid is surprising as an important component of the preparation among the present invention.There are some researches show [Yang Yan, Yin Gongkuan.Diffuse feflectance spec-troscopy research vitamin C and the interactional report of adjuvant.Acta Pharmaceutica Sinica 1988; 23 (2) 152-158], glycine reduces vitamin C stability.Therefore it has been generally acknowledged that at present not salifiable aminoacid be not can with the simultaneous material of vitamin C, in the preparation of Cevalin, also do not make the precedent of Vitamin C preparation pH regulator agent with above-mentioned selected aminoacid.And the application finds can realize the effect as the additive of Vitamin C preparation for specific not salifiable aminoacid-arginine, lysine, histidine by various amino acid whose screenings are investigated.This three seed amino acid does not have negative effect to ascorbic stability.
The application provides a kind of Injectable sterile powder injection composition on the one hand, wherein contain vitamin C and aminoacid, vitamin C and amino acid whose weight ratio are 70-30: 30-70, described aminoacid is one or more mixture of arginine, lysine, histidine, contain the described Injectable sterile powder injection composition of 0.5g vitamin C powder with the cold water 10ml that newly boiled dissolving after in accordance with the law (2000 editions two appendix IXB of Chinese Pharmacopoeia) to measure its pH scope be 4.0-7.5.Vitamin C and amino acid whose weight ratio are 65-50: 35-50 preferably in the compositions, are more preferably 60-50: 40-50.Described aminoacid can be D configuration, L configuration or DL configuration, preferred L configuration.The preferred pH scope of Injectable sterile powder injection composition is 4.5-7.0.
The theory that one of ordinary skill in the art propose according to the present invention, can realize the present invention by vitamin C, aminoacid ratio in any means adjusting preparation of this area, comprise the acceptable acidic excipient auxiliary adjustment of human body pH value such as suitable interpolation citric acid, tartaric acid, and can in preparation, add other adjuvant component according to the general knowledge of this area, as the acceptable adjuvant commonly used of mannitol, pyrophosphate, EDTA or its salt or the like human body.
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 dissolving in each component water, depyrogenation and the aseptic filtration, carries out bottle lyophilizing (or after the deep bid lyophilizing aseptic subpackaged making).
The invention provides the Injectable sterile powder injection composition is used for preventing or treating the medicine of disease in production application on the other hand, described medicine is used for patient's use that needs injection vitamin C is treated, and particularly edema or hypertension etc. are avoided sodium salt disease patient.
Vitamin C, aminoacid 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.Should avoid illumination, oxidation destruction and metal ion pollution in the vitamin C processing procedure.60 ℃ of drying under reduced pressure weightlessness of vitamin C and aminoacid (or moisture) 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 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 L-arginine: get apyrogeneity L-arginine 1.5kg, be dissolved among the water for injection 12L, through 0.22 μ m filter aseptic filtration, under agitation in about 1 hour, add the 60L dehydrated alcohol, separate out crystallization, be cooled to about 0 ℃ again and stirred 2 hours, filter and collect crystallization, a small amount of sterile alcohol washing, 80 ℃ of vacuum dryings get the 0.82kg white solid to constant weight.
Description of drawings
Fig. 1 working sample produces 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: pH value is measured and is undertaken by China national drug standard WS-10001-(HD-0070) 2002 methods.To contain the tested goods powder of vitamin C 0.5g with the cold water 10ml dissolving of newly boiling after, (2000 editions two appendix IXB 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 IVA of Chinese Pharmacopoeia).
Goods dissolving and extraction medicinal liquid: be equivalent to inject 5ml water for injection in the 1g vitamin C goods rapidly and extract syringe needle, rock dissolving.Medicinal liquid extracts with the 10ml syringe.
The sample preparation
Embodiment 1
Get 50g vitamin C, the abundant mix homogeneously of 50g L-arginine of crossing 40 mesh sieves respectively.Every bottle of packing 2g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The arginic weight ratio of vitamin C in the preparation: L-is 50: 50.
Embodiment 2
Get 52.2g vitamin C, the abundant mix homogeneously of 47.8g L-arginine of crossing 40 mesh sieves respectively.Every bottle of packing 1.92g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The arginic weight ratio of vitamin C in the preparation: L-is 52.2: 47.8.
Embodiment 3
Get 58.8g vitamin C, the abundant mix homogeneously of 41.2g L-arginine of crossing 40 mesh sieves respectively.Every bottle of packing 1.7g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The arginic weight ratio of vitamin C in the preparation: L-is 58.8: 41.2.
Embodiment 4
Get 65.3g vitamin C, the abundant mix homogeneously of 34.7g L-arginine of crossing 40 mesh sieves respectively.Every bottle of packing 1.53g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.The arginic weight ratio of vitamin C in the preparation: L-is 65.3: 34.7.
Embodiment 5
Get 50g vitamin C, the abundant mix homogeneously of 50g L-lysine of crossing 40 mesh sieves respectively.Every bottle of packing 2g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-lysine is 50: 50.
Embodiment 6
Get 50.8g vitamin C, the abundant mix homogeneously of 49.2g L-lysine of crossing 40 mesh sieves respectively.Every bottle of packing 1.97g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-lysine is 50.8: 49.2.
Embodiment 7
Get 51.8g vitamin C, the abundant mix homogeneously of 48.2g L-lysine of crossing 40 mesh sieves respectively.Every bottle of packing 1.93g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-lysine is 51.8: 48.2.
Embodiment 8
Get 54.2g vitamin C, the abundant mix homogeneously of 45.8g L-lysine of crossing 40 mesh sieves respectively.Every bottle of packing 1.85g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-lysine is 54.2: 45.8.
Embodiment 9
Get 61.1g vitamin C, the abundant mix homogeneously of 38.9g L-lysine of crossing 40 mesh sieves respectively.Every bottle of packing 1.64g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-lysine is 61.1: 38.9.
Embodiment 10
Get 66.7g vitamin C, the abundant mix homogeneously of 33.3g L-lysine of crossing 40 mesh sieves respectively.Every bottle of packing 1.50g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-lysine is 66.7: 33.3.
Embodiment 11
Get 40.3g vitamin C, the abundant mix homogeneously of 59.7g L-histidine of crossing 40 mesh sieves respectively.Every bottle of packing 2.48g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-histidine is 40.3: 59.7.
Embodiment 12
Get 50g vitamin C, the abundant mix homogeneously of 50g L-histidine of crossing 40 mesh sieves respectively.Every bottle of packing 2.0g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-histidine is 50: 50.
Embodiment 13
Get 60g vitamin C, the abundant mix homogeneously of 40g L-histidine of crossing 40 mesh sieves respectively.Every bottle of packing 1.67g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-histidine is 60: 40.
Embodiment 14
Get 66.7g vitamin C, the abundant mix homogeneously of 33.3g L-histidine of crossing 40 mesh sieves respectively.Every bottle of packing 1.67g (containing the 1g vitamin C), the molded cillin bottle plastic-aluminum of 10ml composite cover packing.Vitamin C in the preparation: the weight ratio of L-histidine is 66.7: 33.3.
Embodiment 15
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) | |||
| Vitamin C | The L-arginine | L-lysine | The L-histidine | |||
| Commercially available sample | 1g vitamin C, 0.25g natrium carbonicum calcinatum | ??4.82 | ??51.9 | |||
| Embodiment 1 | ??50 | ??50 | ??0 | ??0 | ??6.86 | ??0 |
| Embodiment 2 | ??52.2 | ??47.8 | ??0 | ??0 | ??5.23 | ??0 |
| Embodiment 3 | ??58.8 | ??41.2 | ??0 | ??0 | ??4.51 | ??0 |
| Embodiment 4 | ??65.3 | ??34.7 | ??0 | ??0 | ??4.16 | ??0 |
| Embodiment 5 | ??50 | ??0 | ??50 | ??0 | ??5.58 | ??0 |
| Embodiment 6 | ??50.8 | ??0 | ??49.2 | ??0 | ??5.29 | ??0 |
| Embodiment 7 | ??51.8 | ??0 | ??48.2 | ??0 | ??5.09 | ??0 |
| Embodiment 8 | ??54.2 | ??0 | ??45.8 | ??0 | ??4.77 | ??0 |
| Embodiment 9 | ??61.1 | ??0 | ??38.9 | ??0 | ??4.35 | ??0 |
| Embodiment 10 | ??66.7 | ??0 | ??33.1 | ??0 | ??4.09 | ??0 |
| Embodiment 11 | ??40.3 | ??0 | ??0 | ??59.7 | ??5.97 | ??0 |
| Embodiment 12 | ??50 | ??0 | ??0 | ??50 | ??5.41 | ??0 |
| Embodiment 13 | ??60 | ??0 | ??0 | ??40 | ??4.48 | ??0 |
| Embodiment 14 | ??66.7 | ??0 | ??0 | ??33.3 | ??4.12 | ??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.
Too high by the commercially available as can be seen powder sample needle of The above results gas production.
Embodiment 16
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. |
| 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 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 11 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 12 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 13 | Common mode extracts medicinal liquid, and is convenient |
| Embodiment 14 | Common mode extracts medicinal liquid, and is convenient |
Compared with goods among the embodiment as can be seen by The above results, commercially available powder sample needle is difficult to extract medicinal liquid, is inconvenient to use.
Embodiment 17
Carry out the influence factor's test in 10 days of 40 ℃ of high temperature by 2000 editions two ones of Chinese Pharmacopoeias, goods stability the results are shown in Table 3 among more commercially available Vitamin C preparation and the embodiment.
Table 3,10 days influence factor's solution colours of 40 ℃ of high temperature are relatively
| Sample | Trap (420nm) | ||
| 0 day sample | 5 days samples | 10 days samples | |
| Commercially available sample | ??0.015 | ??0.017 | ??0.020 |
| Embodiment 1 | ??0.020 | ??0.024 | ??0.027 |
| Embodiment 12 | ??0.022 | ??0.022 | ??0.024 |
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, the big poor quality of trap.By table 4 as seen, commercially available sample and embodiment sample are all more stable, and specific aminoacid can realize guaranteeing the purpose of vitamin C stable in properties.
Claims (11)
1, a kind of Injectable sterile powder injection composition wherein contains vitamin C and aminoacid; Vitamin C and amino acid whose weight ratio are 70-30: 30-70, described aminoacid is one or more mixture of arginine, lysine, histidine, contain the ascorbic described Injectable sterile powder injection composition powder of 0.5g with the 10ml water dissolution after the pH scope be 4.0-7.5.
2, Injectable sterile powder injection composition as claimed in claim 1, its dissolving back pH scope is 4.5-7.0.
3, Injectable sterile powder injection composition as claimed in claim 1, the described amino acid whose L configuration that is configured as.
4, as claim 1,2 or 3 described Injectable sterile powder injection compositions, wherein said vitamin C and amino acid whose weight ratio are 65-50: 35-50.
5, Injectable sterile powder injection composition as claimed in claim 4, wherein said vitamin C and amino acid whose weight ratio are 60-50: 40-50.
6, Injectable sterile powder injection composition as claimed in claim 4, wherein said aminoacid are L-arginine or L-lysine.
7, Injectable sterile powder injection composition as claimed in claim 3, wherein said aminoacid is the L-histidine, vitamin C and L-histidine weight ratio are 60-40: 40-60.
8, ask the preparation method of the described Injectable sterile powder injection composition of 1-7 as right, it is characterized in that each component raw material in the compositions is mixed the back direct packaging in container.
9,, it is characterized in that being filled to and carrying out lyophilization in the container with after each component raw material dissolving in the compositions as the preparation method of the described Injectable sterile powder injection composition of claim 1-7.
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.
11, application as claimed in claim 10, described patient is that edema or hypertension etc. are avoided sodium salt disease patient.
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| CNB2004100425493A CN100346782C (en) | 2004-05-21 | 2004-05-21 | Vitamin C composition containing amino acids |
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| CNB2004100425493A CN100346782C (en) | 2004-05-21 | 2004-05-21 | Vitamin C composition containing amino acids |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1299676C (en) * | 2005-03-15 | 2007-02-14 | 中国人民解放军第三军医大学 | Anti-anoxia medicinal composition |
| CN104610202A (en) * | 2015-01-30 | 2015-05-13 | 精晶药业股份有限公司 | Preparation method of vitamin C-arginine |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3178451A (en) * | 1962-03-14 | 1965-04-13 | R P Howard & Company | Vitamin c compositions and method of producing same |
| GB1125675A (en) * | 1966-02-10 | 1968-08-28 | Kyowa Hakko Kogyo Kk | Stable ascorbic acid composition and process for preparing the same |
| CN1074371A (en) * | 1993-01-19 | 1993-07-21 | 王景文 | Ascorbic-acid styptic powder |
| EP1423375A2 (en) * | 2001-08-24 | 2004-06-02 | Matthias Rath | Ascorbic acid derivatives, methods of synthesis and pharmaceutical use thereof |
-
2004
- 2004-05-21 CN CNB2004100425493A patent/CN100346782C/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1299676C (en) * | 2005-03-15 | 2007-02-14 | 中国人民解放军第三军医大学 | Anti-anoxia medicinal composition |
| CN104610202A (en) * | 2015-01-30 | 2015-05-13 | 精晶药业股份有限公司 | Preparation method of vitamin C-arginine |
| CN104610202B (en) * | 2015-01-30 | 2017-03-08 | 精晶药业股份有限公司 | A kind of arginic preparation method of vitamin C |
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| CN100346782C (en) | 2007-11-07 |
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Effective date of registration: 20140807 Address after: 850000, Tibet autonomous region Lhasa economic and Technological Development Zone A District Tibet West Cold Chain Logistics Co., Ltd. layer 103 room Patentee after: Tibet Zhong Li Xin Kang medical science and Technology Development Co Ltd Address before: 100085 No. 1, building 2, east gate, No. four, 301 street, Beijing, Haidian District Patentee before: Zhang Yong |
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Address after: 851400 Tibet autonomous region Lhasa economic and Technological Development Zone Incubator Park 1, workshop two, contraction joints to the south room 201-1 Patentee after: Tibet Xingkang pharmaceutical Limited by Share Ltd Address before: 850000, Tibet autonomous region Lhasa economic and Technological Development Zone A District Tibet West Cold Chain Logistics Co., Ltd. layer 103 room Patentee before: Tibet Zhong Li Xin Kang medical science and Technology Development Co Ltd |