阅读说明：本技术 一种用于降血糖的药物组合物、制备方法及应用 (Pharmaceutical composition for reducing blood sugar, preparation method and application ) 是由 俞年军 徐君 周安 程鹤 邢丽花 吴振东 韩荣春 于 2021-01-27 设计创作，主要内容包括：本发明公开一种用于降血糖的药物组合物、制备方法及应用,属于医药和保健品领域；本发明公开了一种用于降血糖的药物组合物,其中,所述多花黄精多糖、枸杞多糖、党参多糖和大枣多糖的摩尔质量比为1-2:1-2:1-2:1；本发明发现多花黄精、枸杞、党参和大枣四种药食同源药材的混合多糖的降血糖作用,比单一多糖降血糖作用效果更好,以此可以开发新的产品,不仅能够更加充分地利用四种药材资源,同时能够使更多的消费者受益。(The invention discloses a pharmaceutical composition for reducing blood sugar, a preparation method and application thereof, belonging to the field of medicines and health care products; the invention discloses a pharmaceutical composition for reducing blood sugar, wherein the molar mass ratio of polygonatum polystachyum polysaccharides, lycium barbarum polysaccharides, codonopsis pilosula polysaccharides and Chinese date polysaccharides is 1-2:1-2:1-2: 1; the invention finds that the hypoglycemic effect of the mixed polysaccharide of four medicinal and edible medicinal materials including polygonatum cyrtonema, medlar, codonopsis pilosula and Chinese date is better than that of the single polysaccharide, so that a new product can be developed, the four medicinal material resources can be more fully utilized, and more consumers can benefit.)

1. A pharmaceutical composition for lowering blood glucose, comprising: the active ingredients of the pharmaceutical composition consist of polygonatum polystachyum polysaccharide, lycium barbarum polysaccharide, codonopsis pilosula polysaccharide and Chinese date polysaccharide according to the molar mass ratio of 1-2:1-2:1-2: 1.

2. The pharmaceutical composition of claim 1, wherein: the molar mass ratio of polygonatum polystachyum polysaccharide to wolfberry polysaccharide to codonopsis pilosula polysaccharide to jujube polysaccharide is 2:2:2: 1.

3. A process for the preparation of a pharmaceutical composition according to claim 1 or 2, wherein the process comprises:

(1) and (3) drying: drying the medicinal materials in an oven at 55 deg.C until the water content is less than or equal to 10% to obtain dried medicinal materials;

(2) crushing: taking the dried medicinal material raw materials, crushing and sieving to obtain medicinal material powder;

(3) degreasing and removing impurities: adding petroleum ether in an amount which is 10 times that of the medicinal material powder, shaking uniformly, refluxing in a water bath at 75 ℃ for 2 hours, performing suction filtration to recover the petroleum ether, and volatilizing residual petroleum ether in a filter cake; adding 10 times of 95% ethanol solution into the filter cake, reflux-extracting for 1.5h, suction-filtering, collecting the filter residue, and drying in a 55 deg.C oven to obtain medicinal material powder filter residue;

(4) extraction: mixing the medicinal material powder filter residue with 15 times of distilled water uniformly, extracting under reflux for 2 times (2 h each time), filtering and collecting filtrate;

(5) concentrating and precipitating: concentrating the obtained filtrate at 60 deg.C under reduced pressure to 1/6 volume of the initial filtrate, slowly adding 95% ethanol and stirring until the final concentration of ethanol is 80%, standing at low temperature, centrifuging, removing supernatant, and collecting precipitate;

(6) and (3) decoloring: sequentially adding 20mL of ethanol, 10mL of acetone and 10mL of diethyl ether into the precipitate, washing for three times, and volatilizing to obtain polysaccharide precipitate;

(7) deproteinization and drying: dissolving the polysaccharide precipitate in distilled water, repeatedly deproteinizing by using a Sevage reagent, adding the Sevage reagent with the volume of 1/3 of the polysaccharide solution, repeating for 3-5 times until no white emulsion exists on the liquid surfaces of the water phase and the Sevage reagent, and freeze-drying the water phase solution to obtain powder, namely the refined medicinal polysaccharide;

(8) mixing the four medicinal material polysaccharides in proportion to obtain the medicinal composition.

4. The production method according to claim 3, characterized in that: in the step (2), the sieving is a No. four sieving.

5. The production method according to claim 3, characterized in that: in the step (7), the Sevage reagent is prepared by mixing the following components in a volume ratio of 4: 1, chloroform and n-butanol.

6. Use of a pharmaceutical composition according to claim 1 or 2 for the preparation of a hypoglycemic product.

7. Use according to claim 6, characterized in that: the product is an oral dosage form medicament or a functional health-care product.

Technical Field

The invention relates to the field of medicines and health-care products, in particular to a pharmaceutical composition for reducing blood sugar, a preparation method and application thereof.

Background

Polygonatum cyrtonema Hua is a perennial herb of Polygonatum of Liliaceae, and its medicinal part is rhizome, sweet and mild in taste. Tonify qi and yin, invigorate spleen, moisten lung and tonify kidney. Can be used for treating spleen deficiency, stomach weakness, asthenia, xerostomia, dry cough due to lung deficiency, essence and blood deficiency, internal heat, and diabetes. Fructus Lycii (Lycium) is a plant of Solanaceae and Lycium, and its medicinal part is fruit, sweet and mild in taste. It is used for nourishing liver, replenishing kidney essence, and moistening lung. Codonopsis pilosula (Franch.) Nannf.) of Campanulaceae, perennial herb with milk, medicinal part with root, sweet and mild taste. Radix Codonopsis has effects of enhancing immunity, dilating blood vessel, lowering blood pressure, improving microcirculation, and improving hemopoiesis function. Fructus Jujubae (Ziziphus jujuba Mill.) is a plant of Ziziphus of Rhamnaceae, turns red after ripening, and its medicinal part is fruit, sweet in taste and warm in nature. The red dates have the main functions of tonifying spleen and stomach, tonifying qi and promoting the production of body fluid, regulating ying and wei and relieving drug toxicity. It is indicated for deficiency of stomach and food, spleen weakness, loose stool, qi, blood and body fluids deficiency, disharmony between ying and wei, palpitation.

Plant polysaccharides, also known as plant polysaccharides, are polysaccharides with a degree of polymerization of more than 10 produced by plant cell metabolism. The plant polysaccharide has relative molecular mass of tens of thousands to more than one million, and comprises glucose, fructose, galactose, arabinose, xylose, rhamnose, fucose, mannose, uronic acid, etc. The main components of plant polysaccharide have differences and are polymerized by several different kinds of monosaccharide according to a certain proportion. Scientific experimental research shows that many plant polysaccharides have biological activity and have health-care effects of immunoregulation, tumor resistance, blood sugar reduction, blood fat reduction, radiation resistance, bacteria resistance, virus resistance, liver protection and the like. Therefore, the plant polysaccharide has been widely applied to the fields of medical science, catering and other public lives.

In the current research, the polysaccharide used for medicines is generally a single polysaccharide, and the biological activity and the hypoglycemic effect are not ideal. The development of a pharmaceutical composition containing complex polysaccharide with high biological activity and good blood sugar reduction effect becomes a research hotspot. At present, the research of four medicinal and edible mixed polysaccharides such as polygonatum polystachyum polysaccharides, lycium barbarum polysaccharides, codonopsis pilosula polysaccharides and Chinese date polysaccharides in blood sugar reduction is not available.

Disclosure of Invention

The invention aims to provide an application of mixed polysaccharide as an active ingredient in preparing a hypoglycemic product so as to solve the problems in the prior art.

In order to achieve the purpose, the invention provides a pharmaceutical composition for reducing blood sugar, wherein the active ingredients of the pharmaceutical composition comprise Polygonatum sibiricum polysaccharide, Lycium barbarum polysaccharide, Codonopsis pilosula polysaccharide and jujube polysaccharide according to the molar mass ratio of 1-2: 1.

Further, the molar mass ratio of the polygonatum polysaccharose, the lycium barbarum polysaccharide, the codonopsis pilosula polysaccharide and the jujube polysaccharide is 2: 1.

The invention also provides a preparation method of the pharmaceutical composition, which comprises the following steps:

(1) and (3) drying: drying the medicinal materials in an oven at 55 deg.C until the water content is less than or equal to 10% to obtain dried medicinal materials;

(2) crushing: taking the dried medicinal material raw materials, crushing and sieving to obtain medicinal material powder;

(3) degreasing and removing impurities: adding petroleum ether in an amount which is 10 times that of the medicinal material powder, shaking uniformly, refluxing in a water bath at 75 ℃ for 2 hours, performing suction filtration to recover the petroleum ether, and volatilizing residual petroleum ether in a filter cake; adding 10 times of 95% ethanol solution into the filter cake, reflux-extracting for 1.5h, suction-filtering, collecting the filter residue, and drying in a 55 deg.C oven to obtain medicinal material powder filter residue;

(4) extraction: mixing the medicinal material powder filter residue with 15 times of distilled water uniformly, extracting under reflux for 2 times (2 h each time), filtering and collecting filtrate;

(5) concentrating and precipitating: concentrating the obtained filtrate at 60 deg.C under reduced pressure to 1/6 volume of the initial filtrate, slowly adding 95% ethanol and stirring until the final concentration of ethanol is 80%, standing at low temperature, centrifuging, removing supernatant, and collecting precipitate;

(6) and (3) decoloring: sequentially adding 20mL of ethanol, 10mL of acetone and 10mL of diethyl ether into the precipitate, washing for three times, and volatilizing to obtain polysaccharide precipitate;

(7) deproteinization and drying: dissolving the polysaccharide precipitate in distilled water, repeatedly deproteinizing by using a Sevage reagent, adding the Sevage reagent with the volume of 1/3 of the polysaccharide solution, repeating for 3-5 times until no white emulsion exists on the liquid surfaces of the water phase and the Sevage reagent, and freeze-drying the water phase solution to obtain powder, namely the refined medicinal polysaccharide;

(8) mixing the four medicinal material polysaccharides in proportion to obtain the medicinal composition.

Further, in the step (2), the sieving is a No. four sieving.

Further, in the step (7), the Sevage reagent is prepared by mixing the Sevage reagent in a volume ratio of 4: 1, chloroform and n-butanol.

The invention also provides application of the pharmaceutical composition in preparing a product for reducing blood sugar.

Furthermore, the product is an oral dosage form medicament or a functional health care product.

The invention discloses the following technical effects: the invention finds that the hypoglycemic effect of the mixed polysaccharide of four medicinal and edible medicinal materials including polygonatum cyrtonema, medlar, codonopsis pilosula and Chinese date is better than the hypoglycemic effect of single polysaccharide, and the polysaccharides of the four medicinal materials have different pharmacological effects respectively, for example, the polygonatum polysaccharide has the effects of bacteriostasis, anti-atherosclerosis, anti-tumor, anti-aging, blood sugar and blood fat regulation, immune regulation, anti-oxidative damage and the like; the functions of the lycium barbarum polysaccharide include antioxidation, anti-aging, immunoregulation, blood fat regulation, blood sugar reduction, radiation resistance, liver cell protection and the like; the Codonopsis pilosula polysaccharide has effects of regulating blood sugar, promoting hematopoiesis, lowering blood pressure, resisting anoxia, relieving fatigue, enhancing immunity, delaying aging, regulating stomach contraction and resisting ulcer; fructus Jujubae polysaccharide has effects of protecting liver, resisting oxidation, resisting aging, relieving fatigue, reducing blood lipid, regulating blood sugar, resisting inflammation, resisting tumor and improving immunity. Therefore, the four medicinal material mixed polysaccharide has other efficacies besides the blood sugar reduction. Therefore, a new product can be developed, not only can the four medicinal material resources be more fully utilized, but also more consumers can benefit.

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.

The present invention will be described in further detail with reference to specific embodiments in order to make the above objects, features and advantages more apparent and understandable.

Example 1 polysaccharide extraction

The polysaccharide is extracted from four medicinal materials including polygonatum cyrtonema, medlar, codonopsis pilosula and Chinese date by the same method, and the specific extraction method comprises the following steps:

(1) and (3) drying: drying the medicinal materials in an oven at 55 deg.C until the water content is not more than 10%.

(2) Crushing: pulverizing the dried raw materials, and sieving with a fourth sieve.

(3) Degreasing and removing impurities: adding 10 times of petroleum ether (boiling range of 60-90 deg.C) into the medicinal powder, shaking, refluxing in 75 deg.C water bath for 2 hr, vacuum filtering to recover petroleum ether, and volatilizing residual petroleum ether in the filter cake. And adding 10 times of 95% ethanol solution into the filter cake, performing reflux extraction for 1.5h, performing suction filtration, collecting filter residue, and drying in an oven at 55 ℃.

(4) Extraction: mixing the medicinal powder residue with 15 times of distilled water, reflux-extracting for 2 times (2 hr each time), vacuum-filtering, and collecting filtrate.

(5) Concentrating and precipitating: the filtrate was concentrated under reduced pressure at 60 ℃ to 1/6 volumes of the initial filtrate, 95% ethanol was slowly added to the filtrate and stirred until the final concentration of ethanol was 80%, and the mixture was left at 4 ℃ overnight and centrifuged.

(6) And (3) decoloring: discarding the supernatant, collecting precipitate, repeatedly adding ethanol, acetone, and diethyl ether (20, 10mL) sequentially, washing for three times, and volatilizing.

(7) Deproteinization and drying: dissolving the polysaccharide precipitate in appropriate amount of distilled water (30mL), repeatedly deproteinizing with Sevage reagent (chloroform: n-butanol 4: 1), adding 1/3 volume of Sevage reagent of polysaccharide solution, repeating for 3-5 times until there is no white emulsion between the water phase and Sevage reagent, and freeze drying the water phase solution to obtain powder which is refined polysaccharide.

Example 2 hypoglycemic action of polysaccharides of four herbs

(1) Grouping: the 200 experimental mice were divided into normal group, control group, model group 1-18, 10 mice each.

(2) An induction model: inducing the mice of the control group and the model groups 1-18 into a diabetic mouse model by using medicaments, taking blood from the tail tip, and measuring the blood sugar of the mice by using blood sugar test paper to judge whether the model building of the diabetic mouse model is successful or not, wherein the specific method comprises the following steps: after the mice were fasted overnight, the next day, STZ solution (50mg/kg, STZ dissolved in citrate buffer, pH 4.2) was intraperitoneally injected. Mice were monitored for blood glucose changes following 5 consecutive days of injection. 7 days later, the mice with the blood sugar concentration more than or equal to 16.7mmol/L are the successful model building.

(3) Gavage was performed on all mice: normal group and control group are given physiological saline, and model group is divided into three groups, and four medicinal materials of mixed polysaccharide (high, medium and low dose), rhizoma Polygonati polysaccharide high dose group and positive drug (metformin) are respectively given.

(4) And (3) analysis: after 4 weeks, blood is taken from the tail tip, and blood sugar of mice in a normal group, a control group and a model group of 1-18 is measured by adopting blood sugar test paper, so that the blood sugar reducing effects of a single medicinal material, a mixture of two medicinal materials, a mixture of three medicinal materials and a mixture of four medicinal materials and polysaccharide are evaluated.

The specific dosing treatments and results are shown in table 1.

TABLE 1

Note:^*is that P is less than 0.05,^**is that P is less than 0.01,^***p is less than 0.05.

As can be seen from Table 1, the blood sugar lowering effect of the mixed polysaccharide of Polygonatum sibiricum Red, Lycium barbarum, Codonopsis pilosula and Zizyphi fructus is superior to that of the polysaccharide of single polysaccharide, the polysaccharide of two kinds of medicinal materials and the polysaccharide of three kinds of medicinal materials. Wherein, the ratio of the polygonatum cyrtonema, the medlar, the codonopsis pilosula and the Chinese date is 2:1, the best effect is achieved, and the blood sugar level of a normal mouse can be basically reached after 4 weeks of administration.

The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.