Composition of disulfide cyclopeptide compound and semeglutide and application of composition in preparation of weight-losing, muscle-protecting and muscle-building drugs

Abstract

The invention relates to the technical field of weight losing and muscle building, in particular to a composition of a disulfide cyclopeptide compound and semeglutide and application of the composition in preparation of weight losing, muscle protecting and muscle building drugs. After the disulfide cyclopeptide compound and the semeglutide are used in a combined manner, the synergistic fat reducing effect is realized, the fat content can be remarkably reduced, and the skin protecting effect is achieved while the fat is reduced.

Description

[0001] This application claims priority to Chinese Patent Application No. 202411230649.2, filed on September 3, 2024, entitled “A Disulfide Ring Peptide Compound and Its Preparation Method and Application”, the entire contents of which are incorporated herein by reference. TECHNICAL FIELD

[0002] The present application relates to the technical field of weight loss and muscle gain, and in particular to a combination of a disulfide ring peptide compound and semaglutide and its application in the preparation of weight loss and muscle preservation and muscle gain drugs. BACKGROUND

[0003] Obesity is a chronic and complex disease characterized by excessive accumulation of fat in the body and adverse effects on health. According to the WHO definition of obesity, the standard for adult obesity is BMI≥30 kg / m 2 Obesity-related diseases include cardiometabolic diseases, digestive system diseases, respiratory system diseases, nervous system diseases, and infectious diseases, significantly increasing healthcare costs.

[0004] There are many types of clinically commonly used weight loss drugs. For example, the latest research on semaglutide shows that the average weight loss of the semaglutide group was 13.9% at week 52, which is better than the placebo group, and 81% of the patients' blood sugar returned to normal. After 28 weeks of drug withdrawal, the semaglutide group still maintained a 7.9% weight loss, and the proportion of blood sugar recovery was also higher than that of the placebo group. This indicates that semaglutide has weight loss and blood sugar recovery effects in patients with prediabetes combined with obesity, and the effects are long-lasting after drug withdrawal. For example, the latest clinical trial of the glucose-dependent insulinotropic polypeptide (GIP) / GLP-1 receptor dual agonist tirzepatide shows that compared with placebo, tirzepatide treatment for 72 weeks can reduce the body weight of subjects by about 20%. Currently, GLP-1 / GIP / glucagon triple agonists, GLP-1 receptor agonists, tyrosine peptide (PYY), and amylin analogs that are still in the clinical drug research and development and clinical trial stages all play a role in weight loss and improving insulin resistance by activating gastrointestinal hormones to regulate central appetite, gastric emptying, and insulin secretion. In addition to new weight loss drugs that regulate gastrointestinal hormones, in recent years, new weight loss drugs targeting the central nervous system and peripheral target organs have also made rapid progress and are expected to be introduced into the clinic in the near future. In the field of central nervous system, tesofensine, as a triple monoamine reuptake inhibitor, promotes weight loss by increasing satiety and reducing food intake, and clinical trials show that it has a significant weight loss effect.

[0005] Patent JP2008519008A discloses new peptide compounds, such as the following formula Ia-Ic:

[0006] They are effective in modulating one or more melanocortin receptor types, the use of the compounds in therapy, methods of treatment, including administering the compounds to a patient in need thereof, and involving the use of the compounds in the manufacture of a medicament. The compounds of the present invention are of particular interest in the treatment of obesity and as a variety of diseases or conditions associated with obesity.

[0007] Traditional anti-obesity drugs have certain therapeutic effects, but have obvious limitations. The administration mode is weekly injection and can easily cause adverse reactions such as nausea, vomiting and diarrhea. More seriously, it can lead to muscle loss, and muscle plays a key role in maintaining healthy weight and overall health.

[0008] Therefore, the focus of anti-obesity drug research and development is to protect muscle and achieve healthy weight loss. SUMMARY

[0009] The purpose of the present application is to provide a combination of a disulfide ring peptide compound and semaglutide and its application in the preparation of a weight loss and muscle protection and muscle increasing drug. It is found in the experimental process that the combination of the disulfide ring peptide compound and semaglutide achieves a synergistic fat loss effect, can significantly reduce fat content, and has a muscle protection effect while losing fat.

[0010] To achieve the above-mentioned purposes of the application, the technical solutions of the present application are as follows: In a first aspect, the present application provides a combination of a disulfide ring peptide compound and semaglutide.

[0011] The disulfide ring peptide compound has the following structure: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2.

[0012] Further preferably, the disulfide ring peptide compound has the following structural formula: .

[0013] Preferably, the preparation method of the disulfide ring peptide compound comprises the following steps: Step 1: selecting a resin and removing a Fmoc protecting group to obtain a resin with a removed Fmoc protecting group; Step 2: weighing Fmoc-R3-OH or Fmoc-Cys(Trt)-OH and PyBop, and coupling the resin with a removed Fmoc protecting group to obtain a coupled resin; Step 3: according to the polypeptide sequence, coupling the coupled resin from the C-terminal to the N-terminal in sequence to obtain a straight-chain peptide resin; Step 4: reacting the cleavage solution with the linear peptide resin to remove the protecting group and obtain a polypeptide; Step 5: dissolving the polypeptide in water, adjusting the pH and adding H2O2 to react to obtain the disulfide cyclic peptide compound.

[0014] Preferably, the weight ratio of the disulfide cyclic peptide compound to semaglutide is 4-24:0.01-0.5.

[0015] More preferably, it is 10-15:0.01-0.2; more preferably, it is 12:0.082-0.164; and most preferably, it is 12:0.123.

[0016] In a second aspect, the present invention provides the use of the above combination in the preparation of drugs for weight loss, muscle preservation and muscle growth.

[0017] Preferably, the weight loss, muscle preservation and muscle gain include at least one of reducing the weight of obese individuals, reducing food intake, reducing fat content and increasing lean meat content.

[0018] In a third aspect, the present invention provides a drug for weight loss, muscle preservation and muscle growth, the active ingredient of which is the above combination.

[0019] Preferably, the weight-loss, muscle-preserving and muscle-building drug further comprises a pharmaceutically acceptable carrier or excipient.

[0020] The phrase "pharmaceutically acceptable carrier" is art-recognized and includes pharmaceutically acceptable materials, components, or vehicles that are suitable for administering the compounds of the present invention to mammals. Carriers include liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials that participate in carrying or transporting the subject substance from one organ or part of the body to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation or not injurious to the subject. Some examples of materials that can serve as pharmaceutically acceptable carriers include: sugars such as lactose, glucose, sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium methyl cellulose, ethyl cellulose, and cellulose acetate; tragacanth, malt, gelatin, talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol, polyols such as glycerol, benzyl alcohol, glycerin, maltose, maltose, talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol, polyols such as glycerol, benzyl alcohol, glycerin, maltose, maltose, talc; Sorbitol, mannitol, and polyethylene glycol, esters such as ethyl oleate and ethyl laurate, agar, buffers such as magnesium hydroxide and aluminum hydroxide, alginic acid, pyrogenic water, isotonic saline, ethanol, phosphate buffered saline, and other nontoxic compatible substances used in pharmaceutical formulations. Wetting agents, emulsifiers, and lubricants such as sodium lauryl sulfate and stearic acid esters, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives, and antioxidants may also be present in the composition.

[0021] Examples of pharmaceutically acceptable antioxidants include: water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, and the like; oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and metal chelates, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.

[0022] Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions (e.g., NaCl), alcohols, gum acacia, vegetable oils, benzyl alcohol, polyethylene glycol, gelatin, sugar (e.g., lactose, amylose or starch), polyvinylpyrrolidone, magnesium stearate, talc, silicic acid, viscous paraffin, perfume oil, fatty acid, cellulose, hydroxy methylcellulose, polyvinyl alcohol, etc. The pharmaceutical compositions can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, coloring, flavoring and / or aromatizing agents, etc. which do not deleteriously react with the active compounds.

[0023] The weight loss and muscle maintenance, muscle building medicaments can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The weight loss and muscle maintenance, muscle building medicaments can be liquid solutions, suspensions, emulsions, tablets, pills, capsules, sustained release formulations, or powders. Compositions can be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration.

[0024] The weight loss and muscle maintenance, muscle building medicaments can be formulated according to conventional pharmaceutical practice in a suitable pharmaceutical composition for administration to humans intravenously. The composition can also contain stabilizing agents and local anesthetics, if desired, to minimize pain at the site of the injection.

[0025] Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampule or articulated tube, or in multiple dose vials containing amounts of the active agents necessary to achieve the desired dosage. Where the weight loss and muscle maintenance, muscle building medicaments are to be administered by infusion, it can be dispensed using an infusion bottle containing sterile pharmaceutical grade water, saline, or aqueous dextrose. Where the weight loss and muscle maintenance, muscle building medicaments are to be administered by injection, an ampule of sterile water for injection or saline can be provided, so that the ingredients can be mixed prior to administration.

[0026] The weight loss and muscle maintenance, muscle building medicaments of the present application can also include agents that control release of the compounds of the present application, to provide a time-release or sustained release composition.

[0027] The weight loss, muscle maintenance, muscle building medicaments of the present application include formulations suitable for oral, rectal, topical, vaginal and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, the nature of the conditions for which the active ingredient is being administered. The pharmaceutical compositions can be prepared by any of the methods well known in the pharmaceutical art.

[0028] The weight loss, muscle maintenance, muscle building medicaments of the present application can be administered orally in solid dosage forms, such as capsules, tablets, troches, dragees, granules, and powders, or in liquid dosage forms, such as elixirs, syrups, emulsions, dispersions, and suspensions. The active ingredient can also be administered parenterally in sterile liquid dosage forms, such as dispersions, suspensions, or solutions. Other dosage forms that can be used to administer the active ingredient are ointments, creams, drops, transdermal patches, or powders for topical administration; eye solutions or suspensions, i.e., eye drops, for administration to the eye; spray or powder compositions for inhalation or intranasal administration; or creams, ointments, sprays, or suppositories for rectal or vaginal administration. Gelatin capsules include the active ingredient in admixture with a powdered carrier such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to prepare compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide sustained release of the medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and to protect the tablet from the atmosphere, or they can be enteric coated for selective disintegration in the gastrointestinal tract. Liquid dosage forms for oral administration can include colorants and flavoring agents to increase patient acceptance. In general, water, suitable oils, saline, dextrose (glucose) in water, and related sugar solutions and glycols such as propylene glycol or polyethylene glycol are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably include water soluble salts of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or in combination, are suitable stabilizing agents. Citric acid and its salts and EDTA sodium can also be used. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

[0029] For administration by inhalation, the compounds of the present application are conveniently delivered from a pressurized pack or a nebulizer. The compounds can also be delivered by means of a powder inhaler which is formulated so as to release the compound in a suitable manner. The preferred delivery system for inhaled administration is a metered dose inhaler (MDI) which can be formulated so as to deliver a compound of Formula I as a suspension or solution in a suitable propellant such as a fluorocarbon or a hydrocarbon. For ophthalmic administration, ophthalmic preparations can be formulated in a suitable weight percent solution or suspension of a compound of Formula I in a suitable ophthalmic vehicle so as to maintain contact of the compound with the surface of the eye for a sufficient time for the compound to penetrate the cornea and interior regions of the eye.

[0030] Useful pharmaceutical dosage forms for administration of the compounds of the present application include, but are not limited to, hard and soft gelatin capsules, tablets, parenteral injections and oral suspensions.

[0031] The same dosage forms as described above can be used when the compounds of the present application are administered stepwise or in combination with other therapeutic agents. When the drugs are administered in a physical combination, the dosage form and the route of administration should be selected according to the compatibility of the combined drugs. The compounds of the present application can be administered as the sole active ingredient or in combination with a second active ingredient, including those known to be useful in the treatment of the relevant disease.

[0032] In a fourth aspect, the present application provides a method for weight loss and muscle maintenance or muscle gain, the method comprising administering to a subject an effective amount of the combination or the weight loss and muscle maintenance or muscle gain agent described above. The method can be used in vivo or in vitro. The subject can be a mammal, such as a human.

[0033] The semaglutide and the disulfide cyclic peptide compound as the active ingredient can be administered simultaneously, for example, mixed together and administered orally, by injection, etc.; or administered separately, for example, one is administered to the subject orally, by injection, etc. first, and the other is administered to the subject orally, by injection, etc. at a suitable time interval.

[0034] Preferably, the administration dose of the semaglutide is 0.01-0.2 mg / kg; and the administration dose of the disulfide cyclic peptide compound is 8-24 mg / kg.

[0035] Preferably, the administration dose of the semaglutide is 0.082-0.164 mg / kg; and the administration dose of the disulfide cyclic peptide compound is 12 mg / kg.

[0036] Further preferably, the administration dose of the semaglutide is 0.123 mg / kg; and the administration dose of the disulfide cyclic peptide compound is 12 mg / kg.

[0037] The weight loss and muscle maintenance, muscle building medicament is a unit dosage form suitable for single administration of an accurate dose. In other embodiments, the amount of the compound is in the range of about 0.001 mg / kg body weight / day to about 1000 mg / kg body weight / day. In other embodiments, the amount of the compound is in the range of about 0.5 mg / kg body weight / day to about 50 mg / kg body weight / day. In some embodiments, the amount of the compound is about 0.001 g / day to about 7 g / day. In other embodiments, the amount of the compound is about 0.002 g / day to about 6 g / day. In other embodiments, the amount of the compound is about 0.005 g / day to about 5 g / day. In other embodiments, the amount of the compound is about 0.01 g / day to about 5 g / day. In other embodiments, the amount of the compound is about 0.02 g / day to about 5 g / day. In other embodiments, the amount of the compound is about 0.05 g / day to about 2.5 g / day. In other embodiments, the amount of the compound is about 0.1 g / day to about 1 g / day. In other embodiments, a dosage level below the lower limit of the above ranges can be sufficient. In other embodiments, a dosage level above the upper limit of the above ranges can be required. In some embodiments, the compound is administered in a single dose, once a day. In other embodiments, the compound is administered in multiple doses, more than once a day. In some embodiments, the compound is administered twice a day. In other embodiments, the compound is administered three times a day. In other embodiments, the compound is administered four times a day. In other embodiments, the compound is administered more than four times a day. In some embodiments, the individual to whom the pharmaceutical composition is administered is a mammal. In other embodiments, the mammal is a human.

[0038] The beneficial effects of the present application are: The present application provides a combination of a disulfide ring peptide compound and semaglutide. The combination of the disulfide ring peptide compound with a specific structure and semaglutide in the present application has a synergistic fat loss effect, further improving the fat loss effect. Compared with high-dose single drug, the fat content is significantly reduced, and the disadvantages of semaglutide in causing muscle loss are improved. The two complement each other, achieving good muscle maintenance effect while losing fat. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 Figure for the weight results of DIO mice in each group on the 48th day of administration.

[0040] Figure 2 Figure for the food intake results of DIO mice in each group on the 10th day of administration Figure 3 Figure for the muscle content change results of DIO mice in each group on the 48th day of administration.

[0041] Figure 4 Figure showing the change in fat content of each group of DIO mice on day 48 of administration. DETAILED DESCRIPTION

[0042] The following non-limiting examples can enable those of ordinary skill in the art to more fully understand the present application, but are not intended to limit the present application in any way. The following merely illustrates the scope of the application claimed, and those skilled in the art can make various changes and modifications to the application disclosed without departing from the scope of the application claimed.

[0043] The present application will be further described in the following specific examples. The various chemical reagents used in the examples of the present application are obtained through conventional commercial channels unless otherwise specified. The amounts described below are mass amounts unless otherwise specified. It is understood that the procedures are carried out at room temperature unless otherwise specified.

[0044] Terms and abbreviations: Ac: acetyl group; Arg: arginine; D-Phe: D-phenylalanine; NH2: amino group; QD: once a day; SC: subcutaneous injection; PBS: phosphate buffered saline; Vehicle: control group.

[0045] Compound preparation: The following compounds were synthesized according to the method described in Example 1 of the priority patent CN119462838A, and the structure characterization was the same as that described in the priority patent CN119462838A.

[0046] WP302-1: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2

[0047] The above compounds are used as experimental drugs, and the information is as follows:

[0048] Fat loss and muscle preservation and muscle gain effect detection: 1. Experimental animals Experimental animals: Beijing VRL Laboratory Animal Technology Co., Ltd. (VRL): C57BL / 6J male mice, 15 weeks old.

[0049] The feeding conditions are as follows: Temperature: 20-26℃; Humidity: 40-70%; Light cycle: 12 hours (7:00 am-19:00 pm); High-fat diet (HFD) feeding: Research Diets, D12492 (Protein: 20% Kcal. Fat: 60 %. Kcal. Carbohydrate: 20% Kcal); Drinking water is pure water (sterilized by high-pressure steam and used after sterilization); Free drinking and drinking water during feeding.

[0050] The high-fat (HFD) induction period of this experiment is 19 weeks, and the efficacy experiment lasts for 9 weeks. The efficacy experiment includes 1 week of screening and baseline collection (high-fat diet induction at week 11) and 8 weeks of treatment period. All obese mice are randomly divided into groups according to the body weight and body fat content during the baseline period before administration.

[0051] 2. Preparation of drug solution: 2.1 Preparation of compound drug solution: Solvent: PBS (Shanghai Shangbao Biotechnology Co., Ltd., T16551, 5012329), 0.01 M, pH 5.5.

[0052] An appropriate amount of compound powder is weighed and dissolved with the solvent to prepare the required concentration of drug solution, and ultrasonic dissolution is used. Prepare once every two to three days, and store the prepared drug solution at 2-8℃ (D0-D30 prepare once every three days, and D35-D53 prepare once every two days).

[0053] 2.2 Preparation of Semaglutide drug solution Solvent: normal saline (0.9% sodium chloride solution) (Shaanxi Shengao Animal Pharmaceutical Co., Ltd., 2408083).

[0054] Drug solution preparation: dissolve Semaglutide powder with solvent to prepare 0.164 mg / mL stock solution, and divide the stock solution into multiple parts according to the weekly usage amount, and store them at -20℃. Semaglutide is prepared once a week, and the frozen compound solution is placed at 2-8℃ before preparation. Dilute with solvent to prepare the drug solution, and store the prepared drug solution at 2-8℃ for 1 week.

[0055] 2.3 Drug administration method The experimental period is 54 days, including D31-D34 and D50, and the drug administration time is 48 days.

[0056] The dosing schedule is as follows (when administered in combination, the two drugs are given consecutively with a short interval):

[0057] 2.4 Experimental Results (1) Body weight was measured at the following times: D-10, D0, D2, D4, D7, D9, D10, D11, D14, D16, D18, D21, D23, D25, D28, D30, D35, D37, D39, D42, D44, D47, D49, and D51 (the first day of administration of the test substance was defined as D0).

[0058] like Figure 1 As shown in the figure, the body weight of animals in the vehicle (PBS) group increased during the administration period, and by the end of the experiment, the body weight increased by 10.7% compared with the baseline value.

[0059] Compared with the Semaglutide alone group and the WP302-1 alone group, the weight loss effect of the WP302-1 and Semaglutide combination group was comparable to that of the Semaglutide alone group, but significantly stronger than that of the WP302-1 alone group. Statistical differences were detected in 13 of the 23 monitoring points.

[0060] (2) Feed intake Animals' daily feed intake fluctuates significantly, so cumulative feed intake is used to represent changes in animal feed intake. Animal feed intake was measured on a cage-by-cage basis, with 1-3 animals per group, so this indicator was not statistically analyzed.

[0061] like Figure 2 As shown, the average daily feed intake of the vehicle (PBS) group did not fluctuate significantly, fluctuating around 2.7 g. After the first dose, the average daily feed intake of each treatment group decreased significantly. Among them, the group containing semaglutide saw the largest decrease, exceeding 70% compared to the baseline value. The other treatment groups saw a decrease of approximately 40% compared to the baseline value. After that, the animals' food intake gradually recovered.

[0062] (3) Body fat scan A QMR06-090H conscious small animal body composition analysis instrument (Suzhou Newmai Analytical Instrument Co., Ltd.) was used with a nuclear magnetic resonance frequency of ≤7 MHz, a coil diameter of 60 mm, and a magnet temperature of 32°C to record muscle and fat content.

[0063] Calculation method for rate of change: The data on the last day of dosing is used as the current value. After successful model establishment, the data on day 0 (before dosing) is used as the baseline value. The formula for calculating the relative baseline rate of change is: Relative baseline change = (Current value - Baseline value) / Baseline value × 100%.

[0064] At the end of the experiment, D49, when the body weights of animals in the Semaglutide alone group and the WP302-1 and Semaglutide combination group were similar, the combination group had lower fat content and higher lean meat content than the Semaglutide alone group.

[0065] like Figure 3 、 Figure 4 As shown in the figure, during the administration period, the lean meat content and fat content of the vehicle group increased with the increase of animal body weight. After correction with body weight, the lean meat percentage decreased and the fat percentage increased, which was consistent with the model trend of DIO animals.

[0066] The body weight of each treatment group decreased compared with the vehicle group, and the lean meat content and fat content were also correspondingly lower than those of the vehicle group. Compared with the vehicle group, the lean meat content of the group containing semaglutide was statistically different from that of the vehicle group, and the fat content of all treatment groups was significantly different from that of the vehicle group.

[0067] After correction for body weight, the lean meat percentage of all drug-treated groups was higher than that of the vehicle group, and the fat content percentage was significantly lower than that of the vehicle group. The lean meat percentage and fat content percentage of all groups were significantly different from those of the vehicle group.

[0068] At the end of the experiment, D49, the fat reduction rate of both the Semaglutide alone group and the WP302-1 and Semaglutide combination group was around 50%. However, the lean meat reduction rate of the WP302-1 and Semaglutide combination group was significantly lower than that of the Semaglutide alone group.

[0069] In summary, the disulfide cyclic peptide compound of the present invention and semaglutide have a synergistic fat-reducing effect when used in combination, further improving the fat-reducing effect. At the same time, it improves the disadvantage of semaglutide in causing muscle loss. The two complement each other and achieve a muscle-preserving effect while reducing fat.

[0070] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A combination of a disulfide cyclic peptide compound and semaglutide, wherein: The disulfide cyclic peptide compound has the following structure: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2.

2. The combination according to claim 1, characterized in that The disulfide cyclic peptide compound has the following structural formula: 。 3. The combination according to any one of claims 1-2, characterized in that The weight ratio of the disulfide cyclic peptide compound to semaglutide is 4-24:0.01-0.

5.

4. The combination according to claim 3, characterized in that The weight ratio of the disulfide cyclic peptide compound to semaglutide is 10-15: 0.01-0.2。 5. The combination according to claim 4, characterized in that The weight ratio of the disulfide cyclic peptide compound to semaglutide is 12:0.082-0.

164.

6. The combination according to claim 5, characterized in that The weight ratio of the disulfide cyclic peptide compound to semaglutide is 12:0.

123.

7. Use of the combination according to any one of claims 1 to 6 in the preparation of drugs for weight loss, muscle preservation and muscle growth.

8. The use according to claim 7, characterized in that The weight loss, muscle preservation and muscle gain include at least one of reducing the weight of obese individuals, reducing food intake, reducing fat content and increasing lean meat content.

9. A drug for losing weight, preserving muscle and increasing muscle mass, characterized in that: The active ingredient is the combination according to any one of claims 1 to 6.

10. The drug for losing weight, preserving muscle and increasing muscle mass according to claim 9, characterized in that: Also included are pharmaceutically acceptable carriers or excipients.

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