阅读说明：本技术 一种1/2水维生素c化合物 (1/2 vitamin C hydrate compound ) 是由 王明 于 2019-12-03 设计创作，主要内容包括：本发明提供一种1/2水维生素C化合物及制法,该化合物用粉末X射线衍射测定法测定,以2θ±0.2°衍射角表示在10.7°,14.3°,15.9°,17.7°,20.0°,25.5°,27.0°,27.4°,32.0°,34.9°,40.5°,43.0°,54.4°处显示出特征衍射峰。本发明制备的1/2水维生素C化合物具有热稳定性好、纯度高、吸湿性弱的优点,而且工艺简单,收率高,重复性强,适合于工业化生产。(The invention provides an 1/2 water vitamin C compound and a preparation method thereof, wherein the compound shows characteristic diffraction peaks at 10.7 degrees, 14.3 degrees, 15.9 degrees, 17.7 degrees, 20.0 degrees, 25.5 degrees, 27.0 degrees, 27.4 degrees, 32.0 degrees, 34.9 degrees, 40.5 degrees, 43.0 degrees and 54.4 degrees by 2 theta +/-0.2 degrees of diffraction angles measured by a powder X-ray diffractometry method. The 1/2 water vitamin C compound prepared by the invention has the advantages of good thermal stability, high purity, weak hygroscopicity, simple process, high yield and strong repeatability, and is suitable for industrial production.)

1. A vitamin C compound, wherein the molecular formula of the vitamin C compound is C₆H₈O₆·¹/₂H₂O, molecular weight of 185.13, structural formula shown in formula (I),

2. the vitamin C compound according to claim 1, wherein the crystalline compound exhibits an X-ray powder diffraction pattern as measured by powder X-ray diffractometry at 2 θ ± 0.2 ° diffraction angles as shown in FIG. 1, and characteristic diffraction peaks at 10.7 °, 14.3 °, 15.9 °, 17.7 °, 20.0 °, 25.5 °, 27.0 °, 27.4 °, 32.0 °, 34.9 °, 40.5 °, 43.0 °, and 54.4 °.

3. The vitamin C compound of claim 1, wherein the preparation method comprises the steps of:

(1) adding 2-keto-L-gulonic acid into a methanol solution, stirring and dissolving, and then carrying out catalytic reaction by using sulfuric acid to obtain 2-keto-L-gulonic acid methyl ester;

(2) cooling to room temperature, adding sodium bicarbonate into the reaction solution, and stirring for reaction to obtain vitamin C sodium salt;

(3) acidifying the reaction solution by ion exchange resin, concentrating the obtained solution under reduced pressure, and drying to obtain a vitamin C crude product;

(4) heating, refluxing and dissolving vitamin C crude product and purified water, adding active carbon for decolorization, performing suction filtration, cooling and crystallizing filtrate in a crystallizing tank, and performing suction filtration;

(5) drying the filtered crystals to obtain the vitamin C compound.

4. The process according to claim 3, wherein the reaction temperature in step (1) is 60 to 70 ℃ and the reaction time is 6.5 to 8.5 hours.

5. The preparation method according to claim 3, wherein the reaction temperature in the step (2) is controlled to be 55-65 ℃ and the reaction time is controlled to be 11-13 h.

6. The method according to claim 3, wherein the concentration temperature in the step (3) is 50 to 55 ℃.

7. The preparation method according to claim 3, wherein in the step (4), the weight ratio of the activated carbon to the purified water is 3.0-4.0:100, the decoloring time of the activated carbon is 5-15min, the crystallization temperature is 0-10 ℃, and the crystallization time is 2-4 h.

8. The preparation method according to claim 3, wherein the drying temperature in the step (5) is 30-40 ℃ and the drying time is 3-5 h.

9. A pharmaceutical composition comprising the vitamin C compound according to any one of claims 1 to 8 and a pharmaceutically acceptable excipient.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to an 1/2 water vitamin C compound and a preparation method thereof.

Background

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin. The molecular formula is as follows: c₆H₈O₆Molecular weight is 176.13, the structural formula is shown as follows,

vitamin C can participate in amino acid metabolism, synthesis of neurotransmitter, synthesis of collagen and interstitial tissue, reduce permeability of capillary, accelerate blood coagulation, stimulate blood coagulation function, promote absorption of iron in intestine, promote blood lipid reduction, increase body resistance to infection, participate in detoxification function, and has antihistaminic effect and effect of preventing generation of carcinogen (nitrosamine). Can be used for the adjuvant treatment of scurvy, various acute and chronic infectious diseases and purpura, etc., and can be used for the timely rescue of keshan disease and cardiogenic shock by large-dose intravenous injection, and can also be used for the treatment of chronic iron poisoning and idiopathic methemoglobinemia.

Vitamin C has strong reducibility, plays a role in regulating redox metabolic reaction, is listed as one of 26 basic medicines by the world health organization, and is a necessary nutrient component for human bodies. Vitamin C is prepared mainly from glucose through microbial fermentation or chemical synthesis, and is widely applied to a plurality of important industrial fields such as medicine, food and beverage, chemical industry, feed and the like. With the increase of the demand of industries such as food, medicine, chemical industry and the like on vitamin C and derivatives thereof, the market competitiveness is increased more and more, and higher requirements are also put forward on the vitamin C conversion and extraction process.

In 1934, German chemist Reichstein and others succeeded in preparing VC by chemical synthesis. In 1937, based on Reichstein et al, people began to use Lee's method for the industrial production of VC. VC is produced by a Leishi chemical method, which takes D-glucose as a raw material, prepares D-sorbitol by catalytic hydrogenation, then generates L-sorbose by acetic acid bacteria fermentation, obtains 2-keto-L-gulonic acid (2-KLC) by ketonization, chemical oxidation and hydrolysis, and obtains VC by hydrochloric acid acidification. The method also has many disadvantages such as complicated production procedure, high labor intensity, and adverse effect on environment.

In the early 70 s of the last century, the microbial research institute of Chinese academy of sciences and Beijing pharmaceutical factory cooperated, and a new technology for preparing VC by a two-step fermentation method was successfully developed. The key steps of the ' two-step fermentation method ' are that L-sorbose which is a product of one-step fermentation by a Lee's method is used as a raw material, the L-sorbose is directly fermented and converted into 2-KLC, then the precursor 2-KLG is directly extracted from fermentation liquor by using weak base ion exchange resin, then methanol-sulfuric acid solution is used for elution, and finally the lactonization and enolization eluent is used for finally becoming vitamin C. However, this method has disadvantages in that 2-KLG as an important intermediate must be chemically converted into vitamin C during the fermentation process, so that chemical reagents are required, and after the fermentation broth is separated and purified, 2-KLG is present in a large amount, which causes environmental pollution, and the discharge of 2-KLG causes waste of resources.

In the traditional process, the preparation method of the vitamin C mainly comprises an acid method and an alkaline method. The acid method takes gulonic acid or sodium gulonate as a raw material and takes acid as a catalyst to generate vitamin C under certain reaction conditions. For example, chinese patent CN104693160A discloses a method for converting sodium gulonate into vitamin C by acid catalysis, which uses high concentration hydrochloric acid and hydrochloric acid gas, and thus has very strict requirements for equipment. In addition, the German BASF group utilizes sodium gulonate to perform esterification reaction under the catalysis of sulfuric acid, and then generates vitamin C through the catalysis of hydrochloric acid.

At present, the raw material of vitamin C in the market is mainly anhydrous, and the raw material medicine has poor stability, low purity, easy oxidation, easy moisture absorption and complex process, and is not convenient for industrial production and storage. The inventor takes the existing 2-keto-L-gulonic acid as a raw material to prepare 1/2-containing vitamin C hydrate compound different from the prior art through a large number of experiments, and the experiment shows that the 1/2-vitamin C hydrate compound has the advantages of good thermal stability, high purity, weak hygroscopicity, simple process, high yield and strong repeatability, and is suitable for industrial production.

Disclosure of Invention

The invention aims to develop and prepare a novel vitamin C compound product, and solves the problems of poor stability, low purity, easy oxidation, easy moisture absorption and the like of vitamin C raw material medicines in the current market. In order to solve the problems, the invention prepares an 1/2 water vitamin C compound.

The invention also provides an 1/2 water vitamin C compound and a preparation method thereof.

The invention also provides a pharmaceutical composition containing 1/2 hydrovitamin C compound.

The technical scheme of the invention is as follows:

1/2A water vitamin C compound with molecular formula of C₆H₈O₆·1/2H₂O, molecular weight of 185.13, structural formula shown below,

an 1/2 hydrovitamin C compound having an X-ray powder diffraction pattern as shown in FIG. 1 at 2 θ ± 0.2 ° diffraction angles showing characteristic diffraction peaks at 10.7 °, 14.3 °, 15.9 °, 17.7 °, 20.0 °, 25.5 °, 27.0 °, 27.4 °, 32.0 °, 34.9 °, 40.5 °, 43.0 °, and 54.4 ° as measured by powder X-ray diffractometry.

A preparation method of 1/2 vitamin C hydrate compound specifically comprises the following steps:

(1) adding 2-keto-L-gulonic acid into a methanol solution, stirring and dissolving, and then carrying out catalytic reaction by using sulfuric acid to obtain 2-keto-L-gulonic acid methyl ester;

(2) cooling to room temperature, adding sodium bicarbonate into the reaction solution, and stirring for reaction to obtain vitamin C sodium salt;

(3) acidifying the reaction solution by ion exchange resin, concentrating the obtained solution under reduced pressure, and drying to obtain a vitamin C crude product;

(4) heating, refluxing and dissolving vitamin C crude product and purified water, adding active carbon for decolorization, performing suction filtration, cooling and crystallizing filtrate in a crystallizing tank, and performing suction filtration;

(5) drying the filtered crystals to obtain the vitamin C compound.

As a preferred embodiment of the invention, the reaction temperature of the step (1) is 60-70 ℃, and the reaction time is 6.5-8.5 h.

As a preferred embodiment of the invention, the reaction temperature of the step (2) is controlled to be 55-65 ℃, and the reaction time is controlled to be 11-13 h.

As a preferred embodiment of the present invention, the concentration temperature in step (3) is 50 to 55 ℃.

As a preferred embodiment of the invention, the weight ratio of the activated carbon to the purified water in the step (4) is 3.0-4.0:100, the decoloring time of the activated carbon is 5-15min, the crystallization temperature is 0-10 ℃, and the crystallization time is 2-4 h.

As a preferred embodiment of the invention, the drying temperature in the step (5) is 30-40 ℃, and the drying time is 3-5 h.

A pharmaceutical composition comprising 1/2 aqueous vitamin C compound of the invention and a pharmaceutically acceptable excipient.

The pharmaceutical composition also contains sodium bicarbonate, sodium metabisulfite, edetate disodium, water for injection and the like.

The pharmaceutical composition is sterile injection prepared from vitamin C, sodium bicarbonate, sodium metabisulfite, edetate disodium and water for injection. The specification contained 2ml:0.25g and 2ml:0.5 g.

Compared with the prior art, the invention has the following advantages:

1. the vitamin C compound provided by the invention has high purity, better thermal stability and basically no moisture absorption.

2. The preparation method of the vitamin C compound provided by the invention has the advantages of simple process, high yield and strong repeatability, and is suitable for industrial production.

3. The pharmaceutical composition containing the vitamin C compound provided by the invention has good stability, so that the medication safety and effectiveness are improved, and the incidence rate of adverse reactions is reduced.

Drawings

Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:

FIG. 1 is an X-ray powder diffraction pattern of a vitamin C compound of the present invention.

Detailed Description

The following examples are further illustrative of the present invention and are in no way intended to limit the scope of the invention. The present invention is further illustrated in detail below with reference to examples, but it should be understood by those skilled in the art that the present invention is not limited to these examples and the preparation method used. Also, equivalent substitutions, combinations, improvements or modifications of the invention may be made by those skilled in the art based on the description of the invention, but these are included in the scope of the invention.