A cyclocarya paliurus compound hypoglycemic composition and a preparation method thereof

Abstract

The application discloses a cyclocarya paliurus compound hypoglycemic composition and a preparation method thereof, and relates to the technical field of traditional Chinese medicines, which is prepared from the following components in a weight ratio: 15 parts of cyclocarya paliurus leaf polyphenol, 20 parts of mulberry leaves, 20 parts of rhizoma polygonati, 10 parts of pericarpium citri reticulatae, 10 parts of American ginseng and 5 parts of selenium-rich viola leaf pteroxygonum stoloniferum peptide; the six components of cyclocarya paliurus leaf polyphenol, mulberry leaves, rhizoma polygonati, pericarpium citri reticulatae, American ginseng and selenium-rich viola leaf pteroxygonum stoloniferum peptide are compounded according to a specific ratio, the synergistic effect of the components is fully exerted, the blood sugar content of high blood sugar model zebra fish is reduced through zebra fish in-vivo experiment verification, and it is indicated that the composition has excellent auxiliary blood sugar lowering effect and is superior to simple superposition of each single component; the preparation method of the application combines ethanol reflux extraction and water extraction to respectively enrich active components in the medicinal materials, the process design is reasonable, stable and controllable, and is suitable for industrialized scale production; and the composition can be added with pharmaceutically or food scientifically acceptable excipients to prepare various dosage forms.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a compound hypoglycemic composition of Eucommia ulmoides and its preparation method. Background Technology

[0002] Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia can lead to chronic damage and dysfunction of multiple organs, including the eyes, kidneys, heart, and blood vessels, and has become a serious global public health problem threatening human health. Currently, commonly used hypoglycemic drugs in clinical practice mainly include biguanides, sulfonylureas, alpha-glucosidase inhibitors, insulin sensitizers, and GLP-1 receptor agonists. While these drugs have a clear hypoglycemic effect, long-term use is often accompanied by varying degrees of adverse reactions, such as weight gain, risk of hypoglycemia, gastrointestinal discomfort, and liver and kidney damage. Therefore, seeking safe and effective adjuvant hypoglycemic active substances from natural products and developing compositions with adjuvant hypoglycemic functions has become a research hotspot in the pharmaceutical and functional food fields.

[0003] *Cyclocarya paliurus* (Batal.) Iljinskaja, also known as the money tree or hemp willow, is a rare tree species endemic to my country, belonging to the genus *Cyclocarya* in the family Juglandaceae. It is mainly distributed in mountainous areas south of the Yangtze River. *Cyclocarya paliurus* leaves are rich in various bioactive components, including flavonoids, triterpenoids, and polysaccharides. In recent years, numerous studies have focused on the extraction and application of these active components. For example, existing patents cover methods for extracting selenium polysaccharides from *Cyclocarya paliurus* (such as CN112568437B) and microwave-assisted aqueous two-phase extraction of triterpenoids from *Cyclocarya paliurus* (such as CN110327385B). However, current research primarily focuses on the extraction and application of single active components (such as polysaccharides and triterpenoids) from *Cyclocarya paliurus*, with limited research on the scientific compounding of polyphenols (flavonoids) from *Cyclocarya paliurus* leaves with various traditional Chinese medicinal herbs. In addition, Qingqianliu has been granted geographical indication protection for agricultural products of the People's Republic of China (first batch in 2021). Among them, Enshi Qingqianliu has attracted much attention due to its unique selenium-rich geographical environment and excellent quality. However, how to make full use of the production advantages of Enshi Qingqianliu and synergistically combine its active ingredients with other medicinal and edible materials to develop a safe, efficient and stable auxiliary hypoglycemic composition is still lacking in systematic research and mature solutions.

[0004] Furthermore, existing Cyclocarya paliurus-related products are mostly crudely processed products made from a single raw material, with simple formulations and a lack of scientific and rational component matching and ratio optimization, resulting in limited hypoglycemic efficacy. While some compound products have increased the variety of excipients, the synergistic effects between the components are unclear, the extraction processes are crude, and the enrichment and bioavailability of active ingredients are low, making it difficult to fully realize the active potential of each herb. Therefore, developing a Cyclocarya paliurus compound hypoglycemic composition with scientifically formulated components, reasonable ratios, controllable extraction processes, and significant hypoglycemic effects has significant practical significance and market value. Summary of the Invention

[0005] In view of the aforementioned existing problems, the present invention is proposed.

[0006] To solve the above-mentioned technical problems, the present invention provides the following technical solution: In a first aspect, the present invention provides a Qingqianliu compound hypoglycemic composition, comprising: It is made from the following components in parts by weight: 15 parts of Eucommia ulmoides leaf polyphenols, 20 parts of mulberry leaves, 20 parts of Polygonatum sibiricum, 10 parts of dried tangerine peel, 10 parts of American ginseng, and 5 parts of selenium-enriched corydalis leaf broken rice peptide.

[0007] As a preferred embodiment of the Qingqianliu compound hypoglycemic composition of the present invention, the dosage form of the composition is tablets, capsules, granules, oral liquid or tea.

[0008] Secondly, the present invention provides a method for preparing a compound hypoglycemic composition based on Eucommia ulmoides, comprising the following steps: (1) Take the leaves of Cyclocarya paliurus, dry and crush them, add solvent to extract them, collect the extract, concentrate and dry them to obtain Cyclocarya paliurus leaf polyphenols; (2) Take mulberry leaves, polygonatum, tangerine peel and American ginseng respectively, dry and crush them, mix them, add water to decoct and extract, filter, collect the filtrate, concentrate and dry to obtain mixed extract; (3) Mix the polyphenols of Cyclocarya paliurus leaf obtained in step (1), the mixed extract obtained in step (2), and selenium-enriched violet leaf crushed rice peptide in a uniform ratio to obtain the Cyclocarya paliurus compound hypoglycemic composition.

[0009] As a preferred embodiment of the preparation method of the present invention, in step (1), the solvent is an aqueous ethanol solution with a concentration of 60% to 90%, the extraction temperature is 60℃ to 90℃, the extraction time is 1 to 3 hours, and the number of extractions is 1 to 3 times.

[0010] As a preferred embodiment of the preparation method described in this invention, in step (2), the amount of water added for the decoction extraction is 6 to 12 times the total weight of the medicinal materials, the decoction temperature is 90℃ to 100℃, the decoction time is 1 to 3 hours, and the number of decoctions is 1 to 3 times.

[0011] As a preferred embodiment of the preparation method described in this invention, in step (3), pharmaceutically or food-grade excipients are added to prepare tablets, capsules, granules, oral liquids or teas.

[0012] Thirdly, the present invention provides the application of the Qingqianliu compound hypoglycemic composition in the preparation of drugs or health foods that assist in lowering blood sugar.

[0013] Beneficial effects of this invention: 1. By combining six components—Qingqianliu leaf polyphenols, mulberry leaves, Polygonatum sibiricum, tangerine peel, American ginseng, and selenium-enriched violet leaf and rice bran peptides—in a specific ratio, the synergistic effect between the components is fully utilized. In vivo experiments with zebrafish have verified that this method can reduce the blood glucose level of zebrafish in a hyperglycemic model, indicating that it has excellent auxiliary hypoglycemic effect, which is superior to the simple superposition of individual components.

[0014] 2. The preparation method of the present invention combines ethanol reflux extraction and water extraction to enrich the active ingredients in each medicinal material. The process design is reasonable, stable and controllable, and suitable for industrial-scale production.

[0015] 3. The composition of the present invention can be formulated into various dosage forms by adding pharmaceutically or food-acceptable excipients. It is convenient to take and has good patient compliance. It can be used as a pharmaceutical preparation for clinical adjuvant hypoglycemia or as a health food for daily dietary supplementation. Attached Figure Description

[0016] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 This is a flowchart of the preparation method of the Qingqianliu compound hypoglycemic composition in Example 1. Detailed Implementation

[0018] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0019] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0020] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0021] Example 1, the first embodiment of the present invention, provides a Qingqianliu compound hypoglycemic composition, comprising: 15 parts of Polyphenols from Eucommia ulmoides leaves, 20 parts of Mulberry leaves, 20 parts of Polygonatum sibiricum, 10 parts of Citrus reticulata peel, 10 parts of American ginseng, and 5 parts of selenium-enriched Corydalis yanhusuo leaf and rice bran peptide.

[0022] Its preparation method is as follows: (1) The leaves of *Cyclocarya paliurus* produced in Enshi City, Hubei Province were dried, pulverized, and then 75% ethanol aqueous solution was added. The mixture was refluxed at 75℃ for 2 hours and extracted twice. The extracts were combined, filtered, and concentrated under reduced pressure to a relative density of 1.10-1.15 (60℃). The extract was then vacuum dried, pulverized and passed through an 80-mesh sieve to obtain *Cyclocarya paliurus* leaf polyphenols. The total flavonoid content was determined by ultraviolet spectrophotometry, with rutin as the reference standard. The total flavonoid content was not less than 55%. (2) Take mulberry leaves, polygonatum, tangerine peel and American ginseng respectively, dry and pulverize them, mix them in the proportion of 20 parts mulberry leaves, 20 parts polygonatum, 10 parts tangerine peel and 10 parts American ginseng, add water 8 times the total weight of the medicinal materials, decoct and extract at 95℃ for 2 hours, extract twice, combine the decoction, filter, concentrate under reduced pressure to an extract with a relative density of 1.10 to 1.15 (60℃), vacuum dry, pulverize and pass through an 80-mesh sieve to obtain a mixed extract; (3) Mix 15 parts of the polyphenols of Cyclocarya paliurus leaf obtained in step (1), the mixed extract obtained in step (2), and 5 parts of selenium-enriched violet leaf crushed rice peptide evenly to obtain the Cyclocarya paliurus compound hypoglycemic composition.

[0023] Example 2, the second embodiment of the present invention, provides a method for preparing a Qingqianliu compound hypoglycemic composition, comprising: (1) Take Cyclocarya paliurus leaves, dry and crush them, add 60% ethanol aqueous solution, reflux extract at 90℃ for 1 hour, extract 3 times, combine the extracts, filter, concentrate under reduced pressure to extract with a relative density of 1.10-1.15 (60℃), vacuum dry, crush and pass through an 80 mesh sieve to obtain Cyclocarya paliurus leaf polyphenols; (2) Take mulberry leaves, polygonatum, tangerine peel and American ginseng respectively, dry and pulverize them, mix them in the proportion of 20 parts mulberry leaves, 20 parts polygonatum, 10 parts tangerine peel and 10 parts American ginseng, add 12 times the total weight of the medicinal materials of water, decoct and extract at 90℃ for 3 hours, extract once, filter, collect the filtrate, concentrate under reduced pressure to an extract with a relative density of 1.10 to 1.15 (60℃), vacuum dry, pulverize and pass through an 80-mesh sieve to obtain the mixed extract; (3) Mix 15 parts of the polyphenols of Cyclocarya paliurus leaf obtained in step (1), the mixed extract obtained in step (2), and 5 parts of selenium-enriched violet leaf crushed rice peptide evenly to obtain the Cyclocarya paliurus compound hypoglycemic composition.

[0024] Example 3 is the third embodiment of the present invention. This embodiment provides a Qingqianliu compound hypoglycemic composition tablet, comprising: The Qingqianliu compound hypoglycemic composition was prepared according to the formulation and preparation method of Example 1. 20 parts of starch (filler), 10 parts of microcrystalline cellulose (filler), 5 parts of sodium carboxymethyl starch (disintegrant), and 0.5 parts of magnesium stearate (lubricant) were added and mixed evenly. The mixture was then wet-granulated, dried, sized, and compressed into tablets to obtain Qingqianliu compound hypoglycemic composition tablets. Each tablet weighs 0.5g and contains 300mg of Qingqianliu compound hypoglycemic composition.

[0025] Comparative Example 1 (single Polyphenols from Eucommia ulmoides leaves, lacking Mulberry Leaf, Polygonatum sibiricum, Citrus reticulata peel, American Ginseng, and Selenium-enriched Corydalis leaf fragments and glutinous rice peptides) The leaves of *Cyclocarya paliurus* were dried, pulverized, and then refluxed with a 75% ethanol aqueous solution at 75°C for 2 hours. The extraction was repeated twice. The extracts were combined, filtered, and concentrated under reduced pressure to a relative density of 1.10–1.15 (60°C). The extract was then vacuum dried, pulverized, and passed through an 80-mesh sieve to obtain *Cyclocarya paliurus* leaf polyphenols.

[0026] Using the same evaluation method for the blood glucose-lowering effect of zebrafish as in Example 1 (see test report TBJ2604006 in the instruction manual), the blood glucose content of zebrafish was measured to be 4.92±0.21mM (n=3) at the same concentration (0.025mg / mL).

[0027] Comparative Example 2 (lacking selenium-enriched corydalis leaf fragments and peptides, the remaining components and proportions are the same as in Example 1) The formula and preparation method of Example 1 are the same, except that selenium-enriched corydalis leaf fragments and ginseng peptides are not added. The product is made from the following components: 15 parts of Eucommia ulmoides leaf polyphenols, 20 parts of mulberry leaves, 20 parts of Polygonatum sibiricum, 10 parts of dried tangerine peel, and 10 parts of American ginseng.

[0028] Using the same evaluation method as in Example 1 for the auxiliary hypoglycemic effect of zebrafish, the blood glucose content of zebrafish was measured to be 4.78±0.25mM (n=3) at the same concentration (0.025mg / mL).

[0029] Comparative Example 3 (The ratio of Cyclocarya paliurus leaf polyphenols was changed beyond the ratio range defined in this invention, while the other components and ratios remained unchanged) The preparation method of Example 1 is the same, except that the ratio of Cyclocarya paliurus leaf polyphenols is changed to 1 part, while the other components remain unchanged. That is, it is made from the following components: 1 part Cyclocarya paliurus leaf polyphenols, 20 parts mulberry leaves, 20 parts Polygonatum sibiricum, 10 parts dried tangerine peel, 10 parts American ginseng, and 5 parts selenium-enriched violet leaf broken rice peptides.

[0030] Using the same method as in Example 1 for evaluating the blood glucose-lowering effect of zebrafish, the blood glucose content of zebrafish was measured to be 4.85 ± 0.22 mM (n = 3) at the same concentration (0.025 mg / mL).

[0031] In summary, this invention combines six components—Cyclocarya paliurus leaf polyphenols, mulberry leaves, Polygonatum sibiricum, tangerine peel, American ginseng, and selenium-enriched corydalis leaf fragments and peptides—in specific weight proportions and employs an optimized extraction process to achieve a synergistic effect among the components. In vivo experiments with zebrafish have verified that this invention can reduce blood glucose levels in a hyperglycemic model zebrafish, demonstrating its excellent adjunctive hypoglycemic effect. Furthermore, the preparation method of this invention is stable, controllable, and easy to operate, suitable for industrial-scale production. It can be formulated into various dosage forms such as tablets, capsules, granules, oral liquids, or teas, making it convenient to take and improving patient compliance. It can be widely applied in the preparation of adjunctive hypoglycemic drugs or health foods.

[0032] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions will not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A compound hypoglycemic composition based on Eucommia ulmoides, characterized in that, It is made from the following components in parts by weight: 15 parts of Polyphenols from Eucommia ulmoides leaves, 20 parts of Mulberry leaves, 20 parts of Polygonatum sibiricum, 10 parts of Citrus reticulata peel, 10 parts of American ginseng, and 5 parts of selenium-enriched Corydalis yanhusuo leaf and rice bran peptide.

2. The Qingqianliu compound hypoglycemic composition as described in claim 1, characterized in that: The composition is available in the form of tablets, capsules, granules, oral liquids, or teas.

3. A method for preparing a Cyclocarya paliurus compound hypoglycemic composition, as described in claim 1 or 2, characterized in that: Includes the following steps: (1) Take the leaves of Cyclocarya paliurus, dry and crush them, add solvent to extract them, collect the extract, concentrate and dry them to obtain Cyclocarya paliurus leaf polyphenols; (2) Take mulberry leaves, polygonatum, tangerine peel and American ginseng respectively, dry and crush them, mix them, add water to decoct and extract, filter, collect the filtrate, concentrate and dry to obtain mixed extract; (3) Mix the polyphenols of Cyclocarya paliurus leaf obtained in step (1), the mixed extract obtained in step (2), and selenium-enriched violet leaf crushed rice peptide in a uniform ratio to obtain the Cyclocarya paliurus compound hypoglycemic composition.

4. The preparation method of the Qingqianliu compound hypoglycemic composition as described in claim 3, characterized in that: In step (1), the solvent is an aqueous ethanol solution with a concentration of 60% to 90%, the extraction temperature is 60℃ to 90℃, the extraction time is 1 to 3 hours, and the extraction is performed 1 to 3 times.

5. The preparation method of the Qingqianliu compound hypoglycemic composition as described in claim 3, characterized in that: In step (2), the amount of water added for the decoction extraction is 6 to 12 times the total weight of the medicinal materials, the decoction temperature is 90℃ to 100℃, the decoction time is 1 to 3 hours, and the decoction is performed 1 to 3 times.

6. The preparation method of the Qingqianliu compound hypoglycemic composition as described in claim 3, characterized in that: In step (3), pharmaceutically or food-grade excipients are added to prepare tablets, capsules, granules, oral liquids or teas.

7. The application of the Cyclocarya paliurus compound hypoglycemic composition according to claim 1 or 2 in the preparation of drugs or health foods that assist in lowering blood sugar.

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