Applications of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or in the preparation of drugs with lipase activity inhibition.

Abstract

This invention relates to the field of pharmaceutical preparation technology, and more particularly to the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or drugs with lipase activity inhibition. This invention provides the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or drugs with lipase activity inhibition. This invention combines purcanapeptide with orlistat, achieving a synergistic effect between the two components. Furthermore, this invention fully considers the composition of the raw materials and the ratio between them, enabling the raw materials to work together in a specific ratio to exert a weight-loss effect.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or in the preparation of drugs with lipase activity inhibition. Background Technology

[0002] Obesity refers to a significant degree of overweight and excessive fat accumulation, a physiological state caused by excessive accumulation of body fat, especially triglycerides. Obesity is primarily due to a disruption of the body's energy metabolism balance, leading to energy intake exceeding energy expenditure and resulting in excessive fat accumulation and metabolic diseases. Obesity is influenced by multiple factors, including genetics, environment, metabolism, and physiology, and is closely related to diseases such as hyperlipidemia, hypertension, diabetes, insulin resistance, hyperuricemia, non-alcoholic fatty liver disease, and coronary atherosclerotic heart disease. Currently, obesity and its complications have become a major public health problem worldwide, affecting not only individual physical appearance but also posing serious threats to human health.

[0003] Plecanatide is a novel drug that affects guanylate cyclase, stimulating intestinal fluid secretion and accelerating defecation. This orally administered polypeptide, composed of 16 amino acids, is designed to mimic the human gastrointestinal peptide uroguanylin for the treatment of chronic idiopathic constipation (CIC) in adults. Plecanatide is an analog of uroguanylin, a cyclic polypeptide containing 16 amino acids, and acts as a guanylate cyclase receptor agonist that promotes sodium excretion. It regulates acid-base balance in the gastrointestinal tract, induces fluid transport into the gastrointestinal tract, and increases peristalsis. However, its application in the preparation of weight-loss drugs has not yet been reported. Summary of the Invention

[0004] The purpose of this invention is to provide the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or in the preparation of drugs with lipase activity inhibition. This invention applies purcanapeptide to the field of weight-loss drug preparation, especially the combination of purcanapeptide and orlistat, which have a synergistic effect.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] This invention provides the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or in the preparation of drugs with lipase activity inhibition.

[0007] Preferably, the lipase is pancreatic lipase.

[0008] Preferably, the drug includes orlistat.

[0009] Preferably, the weight loss refers to non-drug-induced obesity.

[0010] Preferably, the dosage form of the drug is tablet, capsule, pill, solution, powder or granules, suspension or patch.

[0011] Preferably, the mass ratio of purcanapeptide to orlistat is 2-8:20-40.

[0012] Preferably, the mass ratio of purcanapeptide to orlistat is 3-7:25-35.

[0013] Preferably, the mass ratio of purcanapeptide to orlistat is 1:6.

[0014] Compared with the prior art, the present invention has the following beneficial effects:

[0015] 1. This invention provides the application of pulcanapeptide in the preparation of weight-loss drugs, and combines pulcanapeptide with orlistat, achieving a synergistic effect between the two components. Furthermore, this invention fully considers the composition of the raw materials and the ratio between them, enabling the raw materials to work together in specific proportions to exert a weight-loss effect.

[0016] 2. The weight loss composition provided by this invention is a weight loss drug with significant weight loss effect, few toxic side effects, and no weight rebound after discontinuation of the drug, making it an ideal weight loss drug.

[0017] 3. Orlistat is a gastrointestinal lipase inhibitor that can inhibit the absorption of triglycerides, thereby reducing calorie intake and controlling weight. When purcanatide is used in combination with orlistat, purcanatide may further promote the inhibitory effect of orlistat on lipase, thereby achieving the purpose of weight loss. Detailed Implementation

[0018] This invention provides the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or in the preparation of drugs with lipase activity inhibition.

[0019] In this invention, the lipase is pancreatic lipase.

[0020] In this invention, the drug includes orlistat.

[0021] In this invention, the weight loss refers to non-drug-induced obesity.

[0022] In this invention, the dosage form of the drug is tablet, capsule, pill, solution, powder or granules, suspension or patch.

[0023] In this invention, the mass ratio of purcanapeptide to orlistat is 2-8:20-40; preferably 3-7:24-36; more preferably 4-6:28-32; and even more preferably 1:6.

[0024] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0025] Orlistat capsules were purchased from Zhongshan Wanhan Pharmaceutical Technology Co., Ltd. Rats were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Pulcanatide was purchased from Zhejiang Paitai Biotechnology Co., Ltd.

[0026] Example 1

[0027] Comparative experiment:

[0028] 1. Rat selection: 90 SPF-grade rats with an initial weight of 160±5g were randomly divided into 9 groups;

[0029] 2. Feed selection: Commercially available high-fat feeds include 75% basal feed, 2% cholesterol, 0.5% sodium cholate, 15% lard and 7.5% egg yolk.

[0030] 3. Grouping:

[0031] Experimental group: purcanatide dosage was 3.3 mg / kg / d; orlistat dosage was 20 mg / kg / d.

[0032] Control group 1: Pulcanatide dosage was 0.5 mg / kg / day; Orlistat dosage was 20 mg / kg / day.

[0033] Control group 2: Pulcanatide dosage was 16 mg / kg / day; Orlistat dosage was 20 mg / kg / day.

[0034] Control group 3: only purcanatide was used; 3.3 mg / kg / d.

[0035] Existing technology group 1: Orlistat alone; 20 mg / kg / day;

[0036] Existing technology group 2: Orlistat alone; 40 mg / kg / day;

[0037] Existing technology group 3: Orlistat alone; 60 mg / kg / day;

[0038] Blank control group: No drugs were used;

[0039] Model control group: No drugs were used.

[0040] The blank control group was fed a basic diet, while all other groups were fed a high-fat diet.

[0041] 4. Administration of medication:

[0042] All groups were given the medication once a day for 7 weeks.

[0043] 5. Testing Indicators

[0044] (1) Seven weeks after administration, the body weight of each group was observed and recorded;

[0045] (2) At the end of the 7th week after drug administration, the rats were accurately measured in anesthesia before sacrifice, including body length (length from nose to anus) and waist circumference, according to the formula Lee's = (body weight). 1 / 3 ×10 3 Lee's index is calculated based on body length (cm).

[0046] The statistical data for each group are all averaged, and the statistical results are shown in Table 1.

[0047] Table 1

[0048] Weight gain g Waist circumference (cm) Lee's Index experimental group 142.5 16.20 298 Control group 1 168.3 16.38 3.2 Control group 2 161.8 16.29 301 Control group 3 187.3 16.44 308 Existing technology group 1 164.8 16.31 300 Existing technology group 2 151.0 16.16 298 Existing technology group 3 136.5 15.97 297 Blank control group 123.6 15.74 295 Model control group 189.7 16.57 309

[0049] As shown in Table 1, the experimental group's composition exhibits a certain weight-loss effect. With a pulcanapeptide to orlistat ratio of 1:6, the composition's efficacy is superior to that of an equal mass of orlistat. For example, all data from the experimental group are superior to those from the existing technology group 2. This indicates that pulcanapeptide and orlistat can be used in combination. Data from the control group shows that the ratio of pulcanapeptide to orlistat must be appropriate; too high or too low a ratio is not ideal. Furthermore, using pulcanapeptide alone does not produce a weight-loss effect.

[0050] Experiment Example 2

[0051] The effects of each group on the ratio of fat pad to body fat in rats were investigated in Experiment 1. The statistical data for each group were taken as average values. The experimental results are shown in Table 2.

[0052] Table 2

[0053]

[0054]

[0055] The data in Table 2 show that the wet weight of the fat pad in rats fed a high-fat diet was greater than that in rats fed a basal diet, indicating that the high-fat diet contained more fat. Furthermore, comparing the experimental and control groups, purcanatide and orlistat showed better weight loss effects.

[0056] Experimental Example 3

[0057] The diarrhea and fecal condition of rats in each group of Experiment 1 are shown in Table 3.

[0058] Table 3

[0059] Diarrhea rate % fecal condition experimental group 0 No oil stains Control group 1 0 No oil stains Control group 2 20 Oil stains Control group 3 0 No oil stains Existing technology group 1 0 No oil stains Existing technology group 2 10 Slight oil stains Existing technology group 3 20 Oil stains Blank control group 0 No oil stains Model control group 0 No oil stains

[0060] As shown in Table 3, the composition obtained in the experimental group of this invention did not cause diarrhea, indicating that it is a healthy weight-loss drug with low side effects. However, the control group 2 experienced diarrhea, which may be due to excessive addition of purcanatide.

[0061] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The application of purcanatide and orlistat in the preparation of weight-loss and lipid-lowering drugs, characterized in that, The mass ratio of purcanapeptide to orlistat is 1:

6.

2. The application according to claim 1, characterized in that, The weight loss mentioned refers to non-drug-induced obesity.

3. The application according to claim 1, characterized in that, The dosage form of the drug is tablet, capsule, pill, solution, powder or granules, suspension or patch.

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