Application of green lemon pulp alcohol-water extract in preparation of hypoglycemic drugs

Abstract

The invention relates to the technical field of medicines, and particularly provides application of a green lemon pulp alcohol-water extract in preparation of a hypoglycemic medicine. The invention provides a new natural product application scheme for the preparation of hypoglycemic drugs, and has good medicinal value.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and more particularly to the use of a lemon pulp alcohol water extract in the preparation of a hypoglycemic drug. Background Art

[0002] Diabetes is a metabolic disease characterized by chronically elevated blood sugar levels, primarily due to insufficient insulin secretion or insulin resistance (a reduced response to insulin). Disorders of glucose metabolism include pathological conditions such as insulin resistance, impaired glucose tolerance (a decreased ability to regulate blood sugar after oral glucose intake), and hyperinsulinemia, which are often early manifestations or accompanying symptoms of diabetes. Current clinical hypoglycemic medications are primarily chemically synthesized drugs (such as metformin and insulin sensitizers). While they can effectively control blood sugar, long-term use may be associated with side effects such as liver and kidney damage and the risk of hypoglycemia, and some obese patients may experience drug intolerance. At the same time, natural products are gaining attention in the field of glucose metabolism regulation due to their high safety, but existing research has mostly focused on the extraction of single ingredients, with insufficient comprehensive utilization of active ingredients from plant waste.

[0003] Lemons are a common fruit, but the pulp (including the peel, pomace, and seeds) after juicing is often treated as waste, resulting in a waste of resources. Prior research on lemon pulp is limited, and there have been no reports on the systematic application of its extracts in hypoglycemic drugs.

[0004] Furthermore, traditional plant extract preparation processes suffer from low extraction efficiency and significant loss of active ingredients, making them difficult to meet the quality requirements for drug production. Therefore, efficiently utilizing the active ingredients in lemon pulp to develop safe and effective hypoglycemic drugs has become a pressing technical challenge in this field. Summary of the Invention

[0005] The present invention provides an application of a lemon fruit cake alcohol water extract in preparing a blood sugar-lowering drug, which provides a new natural product solution for the preparation of the blood sugar-lowering drug and has good medicinal value.

[0006] In order to achieve these purposes and other advantages according to the present invention, a use of a lemon fruit cake alcohol water extract in the preparation of a hypoglycemic drug is provided.

[0007] Preferably, the blood glucose lowering is manifested as improved oral glucose tolerance.

[0008] Preferably, the blood sugar lowering is manifested as improving oral glucose tolerance caused by obesity.

[0009] Preferably, the kaffir lime dregs alcohol-water extract is prepared by the following steps: adding the dregs after squeezing the juice from fresh kaffir lime fruits to a 95% ethanol aqueous solution at a mass volume ratio of 1 kg / 4-5 L, heating to boiling, reflux extraction for 3-4 hours, filtering to remove the pomace, and volatilizing the extract until there is no alcohol taste, to obtain an extract concentrate, which is the kaffir lime dregs alcohol-water extract.

[0010] Preferably, the medicine is a pharmaceutical composition, which comprises the alcoholic water extract of kaffir lime fruit meal and a pharmaceutically acceptable carrier, and the alcoholic water extract of kaffir lime fruit meal serves as the sole active ingredient of the pharmaceutical composition.

[0011] Preferably, the pharmaceutically acceptable carrier comprises one or more of a filler, a binder, a disintegrant, a lubricant and a flavoring agent.

[0012] Preferably, the drug is prepared into a pharmaceutically acceptable dosage form.

[0013] Preferably, the dosage forms include pills, tablets, powders, capsules, granules, powders, pellets, drops, sprays, injections, suspensions, ointments, gels, and suppositories.

[0014] The present invention has at least the following beneficial effects: The present invention utilizes the active ingredients in the lemon pulp to develop a safe and effective blood sugar regulating drug, which can improve diabetes and sugar metabolism disorders, solve the problems of many side effects of existing blood sugar regulating drugs and insufficient utilization of natural products, and provide a safe and effective drug option for clinical practice.

[0015] Other advantages, objectives and features of the present invention will be reflected in part from the following description and will be understood by those skilled in the art through study and practice of the present invention. DETAILED DESCRIPTION

[0016] The present invention is further described in detail below with reference to examples so that those skilled in the art can implement the invention with reference to the description.

[0017] It should be understood that terms such as “having”, “including” and “comprising” used herein do not preclude the existence or addition of one or more other elements or combinations thereof.

[0018] It should be noted that the experimental methods described in the following embodiments are conventional methods unless otherwise specified, and the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0019] The use of an alcoholic aqueous extract of lime pulp in the preparation of hypoglycemic drugs. Glucose metabolism disorders manifest as a decreased ability of the body to regulate glucose (e.g., elevated blood glucose peaks and slow recovery after oral glucose intake). Diabetes manifests as chronically elevated blood glucose levels, essentially the terminal stage of long-term glucose metabolism disorders. The use of an alcoholic aqueous extract of lime pulp in the preparation of hypoglycemic drugs can improve oral glucose tolerance, particularly in the setting of elevated plasma total cholesterol caused by obesity.

[0020] Kaffir lime, scientifically known as Citrus aurantifolia (Christm.) Swingle, refers to the residual pulp (i.e., waste product, including peel, pomace, and seeds) left after the fresh fruit is washed and directly squeezed for juice. The aqueous extract refers to the mixture of active ingredients obtained by extraction using ethanol and water as the solvent. The preparation of the aqueous extract involves raw material pretreatment (collection and cleaning, drying, and pulverization).

[0021] The blood sugar-lowering drug is a pharmaceutical composition, which includes a kaffir lime fruit meal alcohol water extract and a pharmaceutically acceptable carrier. The kaffir lime fruit meal alcohol water extract is the only active ingredient of the pharmaceutical composition. The pharmaceutically acceptable carrier is a pharmaceutical excipient that does not affect the efficacy of the active ingredient and meets pharmaceutical requirements. The active ingredient and the pharmaceutical excipient are mixed to form a pharmaceutical preparation.

[0022] The pharmaceutically acceptable carrier includes one or more of a filler (lactose, microcrystalline cellulose, corn starch, mannitol, pregelatinized starch, etc.), a binder (hydroxypropyl methylcellulose, polyvinylpyrrolidone, starch slurry, gelatin, polyvinyl alcohol, etc.), a disintegrant (cross-linked polyvinylpolypyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, dry starch, cross-linked sodium carboxymethyl cellulose, etc.), a lubricant (magnesium stearate, micropowdered silica gel, talc, hydrogenated vegetable oil, polyethylene glycol, etc.), and a flavoring agent (sweetener, aromatic, acidulant, masking agent, etc.).

[0023] The drug is prepared into pharmaceutically acceptable dosage forms, including pills, tablets, powders, capsules, granules, powders, dripping pills, drops, sprays, injections, suspensions, ointments, gels, and suppositories. For example, when preparing pills, a lime fruit dregs alcohol water extract extract is taken, dried and crushed into a fine powder, honey is heated and refined into medium honey, mixed with the extract powder in a pan pill pot, and molded with water or dilute ethanol to form a pill core, and the powder and refined honey are gradually added. The pill core is rolled to a suitable size, dried after molding, and can be coated with cinnabar or film as needed to obtain a smooth-looking pill. When preparing tablets, the lime extract dry paste powder is evenly mixed with a filler and a disintegrant, a binder is added to make a soft material, sieved and granulated, and dried. A lubricant is added after the dried granules are granulated, and the tablets are pressed into tablets using a tablet press after mixing. Sugar coating can be performed as needed, and an isolation layer, a powder coating layer, a sugar coating layer, etc. are wrapped in sequence to form a complete tablet. When preparing the injection, the lemon extract is dissolved in water for injection, the pH is adjusted and then filtered and purified, an isotonicity regulator and an antioxidant are added to the filtrate, the mixture is stirred evenly and then filtered through a fused glass funnel, the liquid medicine is filled into an ampoule and sealed, sterilized, and then leak tested with a methylene blue solution, unqualified products are removed, and a sterile injection is obtained.

[0024] 1.1 Preparation of lemon fruit pulp alcohol water extract: Fresh lemon fruits were washed and squeezed directly, and the residual fruit residue (peel, pomace, and seeds) after juicing was heated to boiling with a 95% ethanol-water solution at a mass volume ratio of 1 kg / 4 L. The mixture was refluxed for 3 hours, filtered through 6 layers of gauze to remove the pomace, and the extract was evaporated to dryness until there was no alcohol taste to obtain the extract concentrate.

[0025] 1.2 Materials and Methods 1.2.1 Experimental animals: Female C57BL / 6J mice 1.2.2 Experimental grouping, modeling and drug administration: The mice were divided into the following groups and fed continuously for 16 weeks.

[0026] Normal control group: mice were fed with ordinary feed (D12492B feed), and grew normally without obesity; High-fat modeling group: mice fed with high-fat diet (D12492) became obese; Positive drug group: fed with high-fat diet (D12492) and gavaged with metformin at 250 mg / kg body weight per day; Lemon extract group 1: fed a high-fat diet (D12492) and given lemon extract by gavage at 2.5 mg / kg body weight daily; Lemon extract group 2: The mice were fed a high-fat diet (D12492) and given lemon extract by gavage at 5 mg / kg body weight daily; Lemon extract group 3: fed a high-fat diet (D12492) and given lemon extract by gavage at 10 mg / kg body weight daily; Lemon extract group 4: The mice were fed a high-fat diet (D12492) and given lemon extract by gavage at 20 mg / kg body weight every day.

[0027] 1.3 Blood glucose testing: At the end of the experiment, mice were fasted for 12 hours and weighed. Glucose was dissolved in 0.9% saline (m / v) to obtain a 25% glucose solution (m / v) and administered orally at a dose of 2 g / kg body weight. Blood was drawn from the tail and blood glucose levels were measured. Blood was drawn and tested at the following time points: before gavage (0 min); and 15, 30, 60, 90, and 120 min after gavage. The area under the blood glucose curve (AUC) was calculated. The AUC quantifies the overall magnitude of blood glucose fluctuations after oral glucose administration; larger values indicate poorer blood glucose regulation.

[0028] in, C i For the i Blood glucose value at a certain time point, t i is the time (min), n = 6, a total of 6 time points. The results are shown in Table 1.

[0029] Table 1 As shown in Table 1, the AUC in the obesity model group (1857.66) was significantly higher than that in the normal control group (1408.13), confirming that high-fat diet-induced glucose metabolism disorders are directly related to obesity. Lime extract significantly improved oral glucose tolerance in obese animals, outperforming 10 mg / kg metformin within the tested dose range. A 20 mg / kg dose of lime extract increased the AUC in the oral glucose tolerance test in obese mice to 1364.06 mmol / L, closer to normal levels than the 10 mg / kg atorvastatin group (1521.84 mmol / L). The alcohol-water extract of lemon pulp has a significant hypoglycemic effect on obese mice induced by a high-fat diet. Its mechanism of action may involve activating the AMPK signaling pathway, enhancing the uptake of glucose by muscle and adipose tissue; inhibiting the activity of key enzymes of hepatic gluconeogenesis (such as phosphoenolpyruvate carboxykinase), reducing endogenous glucose production; upregulating the cell membrane translocation efficiency of the glucose transporter GLUT4; improving the adiponectin-insulin signal coupling secreted by adipocytes, optimizing glucose metabolism homeostasis through multiple pathways, and regulating obesity-related blood sugar disorders.

[0030] 1.4 Serum index detection: ELISA kits were used to measure serum glycosylated hemoglobin (HbAlc), insulin, and glucagon-like peptide (GLP-1) in each group of mice. The results are shown in Table 2.

[0031] Table 2 In the glucose metabolism regulatory network, insulin, glycosylated hemoglobin, and glucagon-like peptide (GLP) are key indicators of glucose homeostasis. As shown in Table 2, the obesity model group had significantly higher glycosylated hemoglobin (HbA1c, 1.05 ng / mL) than the control group (0.85 ng / mL), with a compensatory increase in serum insulin (0.80 ng / mL) and a significant decrease in GLP-1 (0.15 ng / mL). This confirms that high-fat diet-induced glucose metabolism disorders, accompanied by insulin resistance and suppressed incretin secretion, are directly related to obesity. An alcoholic aqueous extract of kaffir lime pulp has shown promising results in regulating glucose metabolism. Within the tested dose range, the 20 mg / kg dose reduced HbA1c to 0.92 ng / mL, serum insulin to 0.65 ng / mL, and GLP-1 to 0.28 ng / mL in obese mice, bringing them closer to normal levels compared to the 10 mg / kg dose (HbA1c 0.95 ng / mL, GLP-1 0.25 ng / mL). This alcoholic aqueous extract significantly modulated glucose metabolism in obese mice induced by a high-fat diet, particularly in obesity-induced impaired oral glucose tolerance and insulin resistance. Its mechanism of action may be through activating the AMPK pathway, promoting GLUT4 membrane translocation and enhancing peripheral glucose uptake; inhibiting the activity of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase in the liver, reducing hepatic glucose output; and, through repairing intestinal L cells, promoting GLP-1 secretion and improving adiponectin-insulin signaling in adipocytes, thereby synergistically optimizing glucose homeostasis.

[0032] The number of devices and processing scales described herein are intended to simplify the description of the present invention. Applications, modifications, and variations of the present invention will be readily apparent to those skilled in the art.

[0033] Although the embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the description and implementation methods. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and examples shown and described herein.

Claims

1. Application of lemon fruit cake alcohol water extract in the preparation of hypoglycemic drugs.

2. The use according to claim 1, characterized in that Hypoglycemic effects are manifested as improved oral glucose tolerance.

3. The use according to claim 2, characterized in that Lowering blood sugar is manifested as improving oral glucose tolerance caused by obesity.

4. The use according to claim 1, wherein The kaffir lime dregs alcohol-water extract is prepared by the following steps: adding the dregs after squeezing the juice from fresh kaffir lime fruits to an ethanol aqueous solution with a volume fraction of 95% at a mass volume ratio of 1 kg / 4-5 L, heating to boiling, reflux extraction for 3-4 hours, filtering to remove the pomace, and volatilizing the extract until there is no alcohol taste to obtain an extract concentrate, which is the kaffir lime dregs alcohol-water extract.

5. The use according to claim 1, characterized in that The medicine is a pharmaceutical composition, which comprises the kaffir lime fruit meal alcohol water extract and a pharmaceutically acceptable carrier, and the kaffir lime fruit meal alcohol water extract serves as the only active ingredient of the pharmaceutical composition.

6. The use according to claim 5, characterized in that The pharmaceutically acceptable carrier includes one or more of a filler, a binder, a disintegrant, a lubricant and a flavoring agent.

7. The use according to claim 1, wherein The drug is prepared into a pharmaceutically acceptable dosage form.

8. The use according to claim 7, characterized in that The dosage forms include pills, tablets, powders, capsules, granules, powders, pellets, drops, sprays, injections, suspensions, ointments, gels, and suppositories.

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