阅读说明：本技术 一种稳定的脂溶性维生素c制剂及其制备方法 (Stable fat-soluble vitamin C preparation and preparation method thereof ) 是由 不公告发明人 于 2020-05-26 设计创作，主要内容包括：本发明提出了一种稳定的脂溶性维生素C制剂,其含有新型的维生素C琥珀酸酯衍生物,所述新型的维生素C琥珀酸酯衍生物具有如下式Ⅰ结构；本发明合成的新型的维生素C琥珀酸酯衍生物制备方法简单,改善维生素C的稳定性、脂溶性和生物相容性的同时,可将两者的作用有机结合,使其功效更优越,另一方面,也降低了制备成本,提高了吸收效果,具有广阔的应用前景。<Image he="483" wi="496" file="DDA0002509568930000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention provides a stable fat-soluble vitamin C preparation, which contains a novel vitamin C succinate derivative, wherein the novel vitamin C succinate derivative has a structure shown in the formula I; the novel vitamin C succinate derivative synthesized by the invention has a simple preparation method, improves the stability, fat solubility and biocompatibility of the vitamin C, and can organically combine the functions of the vitamin C and the vitamin C to ensure that the vitamin C has more excellent efficacy.)

1. A stable, fat-soluble vitamin C formulation comprising a novel vitamin C succinate derivative having the formula I:

2. the stable fat-soluble vitamin C formulation of claim 1, further comprising microcrystalline cellulose, cyclodextrin, modified starch, talc.

3. The stable fat-soluble vitamin C formulation of claim 1, wherein the cyclodextrin is selected from the group consisting of methyl- β -cyclodextrin, dimethyl- β -cyclodextrin, hydroxyethyl- β -cyclodextrin, hydroxypropyl- β -cyclodextrin, sulfomethyl ether- β -cyclodextrin, sulfobutyl ether- β -cyclodextrin, and maltosyl- β -cyclodextrin, in a mixture.

4. The stable fat-soluble vitamin C preparation according to claim 2, comprising the following raw materials in parts by weight: 65-75 parts of novel vitamin C succinate derivative, 1-5 parts of microcrystalline cellulose, 1.2-3 parts of cyclodextrin, 0.3-1 part of modified starch and 2.2-5.5 parts of talcum powder.

5. The stable fat-soluble vitamin C formulation as claimed in claim 1, wherein said novel vitamin C succinate derivative is prepared by the following method: dissolving vitamin C and succinic acid in water, heating to 40-45 ℃, adding lipase for mixing, performing microwave treatment, stirring for reaction for 5-10h, removing the solvent under reduced pressure, pouring the mixture into a mixture of ethyl acetate and ice water, stirring and washing for 10min, filtering, washing with distilled water, and performing vacuum drying at 50-70 ℃ to obtain solid powder which is the novel vitamin C succinate derivative.

6. The stable fat-soluble vitamin C formulation as claimed in claim 5, wherein the microwave treatment power is 800-1200W.

7. The stable fat-soluble vitamin C formulation according to claim 1, wherein the volume ratio of ethyl acetate to ice water in the mixture of ethyl acetate and ice water is 1: 1; the ratio of the vitamin C to the succinic acid is 1: (1.1-1.3), wherein the addition mass ratio of the vitamin C to the lipase is 1: (0.05-0.2).

8. A process for the preparation of a stable fat-soluble vitamin C formulation as claimed in any one of claims 1 to 7, comprising the steps of:

s1, sieving a novel vitamin C succinate derivative and cyclodextrin respectively, and mixing uniformly to obtain a mixed material;

s2, adding modified starch and microcrystalline cellulose into the mixed material, spraying an ethanol solution to prepare a soft material, granulating, drying, finishing granules, adding talcum powder, and uniformly mixing;

s3, encapsulating or tabletting.

9. The production method according to claim 8, wherein the concentration of the ethanol solution is 60 to 70 wt%, and the amount sprayed is 0.1 to 0.2 wt% of the total mass.

10. The stable fat-soluble vitamin C formulation according to claim 1, wherein the novel vitamin C succinate derivative is replaced by a novel vitamin C maleate derivative, wherein the novel vitamin C maleate derivative has the following structure (II):

Technical Field

The invention relates to the technical field of biological preparations, in particular to a stable fat-soluble vitamin C preparation and a preparation method thereof.

Background

Vitamin C has high medicinal value, but the vitamin C also has the defect of poor stability, and a way for converting the vitamin C into a substance with good stability is always searched for by human beings, but the way for converting the vitamin C into a derivative is the only way at present. In recent years, new physiological functions and medicinal values of vitamin C are continuously developed, and thus, receiving wide attention in the world, researchers apply the vitamin C to research on treatment of various diseases and expect more important findings, but the application of vitamin C is still limited by its natural properties. Since vitamin C is very unstable to physicochemical factors and relatively hydrophilic and not easy to pass through cell membranes, it is necessary to use vitamin C in many cases for treating diseases, and if the amount of vitamin C is relatively small, it is likely to become an oxidation enhancer, so that the use of a large amount of vitamin C is required. On the other hand, however, gastrointestinal functions may be disturbed by the administration of a large amount of vitamin C, and more seriously, urinary calculi may be caused thereby. Under the contradiction between the two aspects, a novel vitamin C derivative has to be developed, on one hand, the storage time of the vitamin C in the body can be prolonged by improving the stability of the vitamin C, and the sensitivity of the vitamin C to metal ions can be weakened, so that the vitamin C derivative can not become an oxidation enhancer; on the other hand, the permeability of the cell membrane can be improved, and the active oxygen free radicals can be cleared away by the cell. By adopting the method, the vitamin C can be taken as little as possible under the condition of ensuring the same treatment effect, and the vitamin C is prevented from generating some adverse side effects.

Disclosure of Invention

The invention aims to provide a stable fat-soluble vitamin C preparation and a preparation method thereof, the preparation method is simple, the stability, fat solubility and biocompatibility of the vitamin C are improved, and simultaneously the effects of the vitamin C and the fat-soluble vitamin C can be organically combined, so that the effect of the vitamin C is more excellent, on the other hand, the preparation cost is also reduced, and the absorption effect is improved.

The technical scheme of the invention is realized as follows:

the present invention provides a stable fat-soluble vitamin C formulation comprising a novel vitamin C succinate derivative having the following formula i:

as a further improvement of the invention, the starch adhesive also comprises microcrystalline cellulose, cyclodextrin, modified starch and talcum powder.

As a further improvement of the invention, the cyclodextrin is selected from one or a mixture of several of methyl-beta-cyclodextrin, dimethyl-beta-cyclodextrin, hydroxyethyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, sulfomethyl ether-beta-cyclodextrin, sulfobutyl ether-beta-cyclodextrin and maltosyl-beta-cyclodextrin.

As a further improvement of the invention, the feed comprises the following raw materials in parts by weight: 65-75 parts of novel vitamin C succinate derivative, 1-5 parts of microcrystalline cellulose, 1.2-3 parts of cyclodextrin, 0.3-1 part of modified starch and 2.2-5.5 parts of talcum powder.

As a further improvement of the invention, the novel vitamin C succinate derivative is prepared by the following method: dissolving vitamin C and succinic acid in water, heating to 40-45 ℃, adding lipase for mixing, performing microwave treatment, stirring for reaction for 5-10h, removing the solvent under reduced pressure, pouring the mixture into a mixture of ethyl acetate and ice water, stirring and washing for 10min, filtering, washing with distilled water, and performing vacuum drying at 50-70 ℃ to obtain solid powder which is the novel vitamin C succinate derivative.

As a further improvement of the invention, the microwave treatment power is 800-.

As a further improvement of the invention, the volume ratio of the ethyl acetate to the ice water in the ethyl acetate and ice water mixture is 1: 1; the ratio of the vitamin C to the succinic acid is 1: (1.1-1.3), wherein the addition mass ratio of the vitamin C to the lipase is 1: (0.05-0.2).

The invention further provides a preparation method of the stable fat-soluble vitamin C preparation, which comprises the following steps:

s1, sieving a novel vitamin C succinate derivative and cyclodextrin respectively, and mixing uniformly to obtain a mixed material;

s2, adding modified starch and microcrystalline cellulose into the mixed material, spraying an ethanol solution to prepare a soft material, granulating, drying, finishing granules, adding talcum powder, and uniformly mixing;

s3, encapsulating or tabletting.

As a further improvement of the invention, the concentration of the ethanol solution is 60-70 wt%, and the spraying amount is 0.1-0.2 wt% of the total mass.

As a further improvement of the present invention, the novel vitamin C succinate derivative can be replaced with a novel vitamin C maleate derivative having the following formula ii:

the invention has the following beneficial effects: succinic acid, also called succinic acid, is amber formed by burying resin from Pinus plants underground for a long time, also widely exists in various plants and animal tissues, can be used for treating rheumatic inflammatory pain and treating chronic urethritis by oral administration, is a safe nutritional additive, prepares a novel vitamin C succinate derivative by esterification reaction of vitamin C and succinic acid, improves the stability and fat solubility of the vitamin C, and can organically combine the functions of the vitamin C succinate derivative and the succinic acid so as to have more excellent efficacy; meanwhile, succinic acid can be replaced by maleic acid, and the prepared vitamin C maleate derivative has similar stability, fat solubility and biocompatibility;

the microcrystalline cellulose has good adhesion and proper hygroscopicity, and can also be used as a heat stabilizer and a quick-drying carrier, and after the microcrystalline cellulose is compounded with modified starch, the dosage of the microcrystalline cellulose is reduced, but the adhesion is enhanced, so that the cost is reduced, and a better granulation effect is achieved; the cyclodextrin has better absorption promotion performance, and improves the biocompatibility and the absorbability of the vitamin C preparation, so that the effect is better than that of the traditional preparation process of the vitamin C by adding less vitamin C.

The novel vitamin C succinate derivative synthesized by the invention has a simple preparation method, improves the stability, fat solubility and biocompatibility of the vitamin C, and can organically combine the functions of the vitamin C and the vitamin C to ensure that the vitamin C has more excellent efficacy.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.

FIG. 1 is a graph showing the comparison of the hydroxyl radical (. OH) scavenging ability of each group in test example 2 of the present invention;

FIG. 2 is a graph showing a comparison of the DPPH radical scavenging ability of each group in test example 2 of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.