Application of disulfide cyclopeptide compound in preparation of weight-losing, muscle-protecting and muscle-building medicine

Abstract

The invention relates to the technical field of weight losing and muscle building, in particular to application of a disulfide cyclopeptide compound in preparation of weight losing, muscle protecting and muscle building drugs. The disulfide cyclopeptide compound has the following structure: R2-R1-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, the compound with the structure can significantly reduce body weight and food intake, has a muscle protection effect while losing weight, and widens the application field of the disulfide cyclopeptide compound at the same time.

Description

[0001] This application claims priority to: Chinese patent application number 202411230649.2, filed by Wanbangde Pharmaceutical Group Co., Ltd. on September 3, 2024, entitled "A disulfide cyclic peptide compound, its preparation method and application", the entire contents of which are incorporated herein by reference. Technical Field

[0002] The present invention relates to the technical field of weight loss and muscle building, in particular to the application of a disulfide cyclic peptide compound in the preparation of weight loss, muscle preservation and muscle building drugs. Background Art

[0003] Obesity is a chronic and complex disease characterized by excessive accumulation of body fat and adverse health effects. 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, neurological diseases, and infectious diseases, which significantly increase healthcare expenditures.

[0004] A wide range of weight loss medications are commonly used clinically. For example, a recent study of semaglutide showed that the average weight loss in the semaglutide group at week 52 was 13.9%, superior to that in the placebo group, and 81% of patients had normal blood sugar levels. Twenty-eight weeks after discontinuation of the drug, the semaglutide group maintained a 7.9% weight loss, and the blood sugar recovery rate was also higher than in the placebo group. This suggests that semaglutide has weight loss and blood sugar recovery effects in patients with prediabetes and obesity, and that the effects are persistent after discontinuation. Another example is the recent clinical trial of telpotide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) / GLP-1 receptor, which showed that telpotide treatment resulted in approximately 20% weight loss compared to placebo over 72 weeks. GLP-1 / GIP / glucagon triple agonists, as well as GLP-1 receptor agonists, peptide tyrosine yrosine (PYY), and amylin analogs, which are currently in the clinical drug development and clinical trial stages, all regulate central appetite, gastric emptying, and insulin secretion by activating gastrointestinal hormones to achieve weight loss and improve insulin resistance. In addition to new weight-loss drugs that regulate gastrointestinal hormones, recent years have also seen rapid progress in the development of new weight-loss drugs targeting the central nervous system and peripheral organs, with the hope of entering clinical trials in the near future. In the central nervous system, Tesofensine, a triple monoamine reuptake inhibitor, promotes weight loss by increasing satiety and reducing food intake. Clinical trials have demonstrated significant weight-loss efficacy.

[0005] Patent JP2008519008A discloses novel peptide compounds, as shown in the following formulas Ia-Ic:

[0006] The compounds are effective for modulating one or more melanocortin receptor types, and their use in therapy, methods of treatment comprising administering the compounds to a patient in need thereof, and use of the compounds in the preparation of medicaments. The compounds of the invention are particularly interesting for treating obesity and various diseases or conditions associated with obesity.

[0007] While traditional anti-obesity drugs have some efficacy, they have significant limitations. They require weekly injections and are prone to side effects such as nausea, vomiting, and diarrhea. More seriously, they can lead to muscle loss, which plays a key role in maintaining a healthy weight and overall health.

[0008] Therefore, the focus of anti-obesity drug research and development is on protecting muscle while achieving healthy weight loss. Summary of the Invention

[0009] The purpose of the present invention is to provide the use of a disulfide cyclic peptide compound in the preparation of a weight-loss, muscle-preserving, and muscle-building drug. The compound of this structure can significantly reduce body weight and food intake, and has a muscle-preserving effect while losing weight, while also broadening the application field of the disulfide cyclic peptide compound.

[0010] In order to achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows: In a first aspect, the present invention provides a disulfide cyclic peptide compound for use in preparing a drug for weight loss, muscle preservation, and muscle growth, wherein the disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

[0011] Preferably, R1 is Arg; R2 is an acetyl group or a palmitoyl group; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is an amino group; Furthermore, when R3 is absent, R2 is a palmitoyl group.

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

[0013] Wherein, R1, R2, R3 and R4 are as defined above.

[0014] Further preferably, R3 is selected from Ile, D-Phe, Pro or deletion, and R1 is Arg.

[0015] Further preferably, R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

[0016] Further preferably, when R3 is absent, R4 is a palmitoyl group.

[0017] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds:

[0018] .

[0019] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: .

[0020] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: 、 .

[0021] Preferably, the preparation method of the disulfide cyclic peptide compound comprises the following steps: Step 1: Select a resin and remove the Fmoc protecting group to obtain a resin from which the Fmoc protecting group has been removed; Step 2: Weigh Fmoc-R3-OH or Fmoc-Cys(Trt)-OH and PyBop, and perform a coupling reaction on the resin with the Fmoc protecting group removed to obtain a coupled resin; Step 3: According to the peptide sequence, the coupling resin is coupled from the C-terminus to the N-terminus to obtain a linear 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.

[0022] 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.

[0023] In a second aspect, the present invention provides a drug for weight loss, muscle preservation and muscle growth, the active ingredient of which is a disulfide cyclic peptide compound.

[0024] Preferably, the drug for losing weight, preserving muscle and increasing muscle further comprises a pharmaceutically acceptable carrier or excipient.

[0025] Wherein, the disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

[0026] Preferably, R1 is Arg; R2 is an acetyl group or a palmitoyl group; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is an amino group; Furthermore, when R3 is absent, R2 is a palmitoyl group.

[0027] Further preferably, the disulfide cyclic peptide compound has the following structural formula:

[0028] Wherein, R1, R2, R3 and R4 are as defined above.

[0029] Further preferably, R3 is selected from Ile, D-Phe, Pro or deletion, and R1 is Arg.

[0030] Further preferably, R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

[0031] Further preferably, when R3 is absent, R4 is a palmitoyl group.

[0032] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds:

[0033] .

[0034] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: .

[0035] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: 、 .

[0036] 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 deleterious to the subject. Some examples of materials that can serve as pharmaceutically acceptable carriers include: sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium methylcellulose, ethylcellulose, and cellulose acetate; tragacanth, malt, gelatin, and 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, sorbitol, mannitol, and polyethylene glycol, esters such as ethyl oleate and ethyl laurate, agar, buffers such as magnesium hydroxide and aluminum hydroxide, alginic acid, pyrogen water, isotonic saline, ethanol, phosphate buffer, and other non-toxic, compatible substances used in pharmaceutical formulations. Wetting agents, emulsifiers, and lubricants such as sodium lauryl sulfate and stearic acid, as well as colorants, release agents, coating agents, sweeteners, flavoring and perfuming agents, preservatives, and antioxidants may also be present in the composition.

[0037] Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants, such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, etc.; oil-soluble antioxidants, such as ascorbyl palmitate, butylated benzoic acid (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc.; and metal complexes, such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc.

[0038] Suitable pharmaceutically acceptable carriers include, but are not limited to, water, saline solutions (e.g., NaCl), alcohol, gum arabic, vegetable oils, benzyl alcohol, polyethylene glycol, gelatin, sugars (e.g., lactose, amylose, or starch), polyethylene glycol, magnesium stearate, talc, silicic acid, viscous paraffin, essential oils, fatty acid esters, methylcellulose, polyvinylpyrrolidone, etc. The pharmaceutical composition can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salt buffers for influencing osmotic pressure, colorants, flavorings, and / or aromatic substances, which do not deleteriously react with the active compounds.

[0039] The weight-loss, muscle-preserving, and muscle-building drugs may also contain minor amounts of wetting agents, emulsifiers, or pH buffers. The weight-loss, muscle-preserving, and muscle-building drugs may be in the form of liquid solutions, suspensions, emulsions, tablets, pills, capsules, sustained-release formulations, or powders. The compositions may be formulated into suppositories with conventional binders and carriers (e.g., triglycerides). Oral formulations may include standard carriers such as pharmaceutical-grade mannitol, lactose, magnesium stearate, polyvinylpyrrolidone, saccharin sodium, cellulose, and magnesium carbonate.

[0040] According to conventional methods, the muscle-building and weight-loss drugs can be formulated into pharmaceutical compositions suitable for intravenous administration to humans. If necessary, the compositions can also include stabilizers and local anesthetics to alleviate pain at the injection site.

[0041] Typically, the ingredients are supplied separately or mixed together in unit dosage form, for example as a dry lyophilized powder or anhydrous concentrate in a sealed container such as an ampoule or a sachet indicating the amount of active agent. When the weight-loss, muscle-preserving, or muscle-building drug is to be administered by infusion, it can be dispersed using an infusion bottle containing pharmaceutical grade sterile water, saline, or dextrose water. When the weight-loss, muscle-preserving, or muscle-building drug is to be administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients can be mixed before administration.

[0042] The muscle-loss, muscle-preserving and muscle-building drugs of the present invention may also include agents for controlling the release of the compounds of the present invention, thereby providing time-controlled or sustained-release compositions.

[0043] The weight loss, muscle preservation, and muscle building drugs of the present invention include formulations suitable for oral, rectal, topical, vaginal, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most appropriate route in any particular case depends on the specific subject, the nature, and severity of the condition to which the active ingredient is administered. The pharmaceutical compositions can be prepared by any method known in the art of pharmacy.

[0044] The muscle-building and weight-loss drugs described herein can be administered orally in solid or liquid dosage forms, such as capsules, tablets, lozenges, troches, 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 include ointments, creams, drops, transdermal patches, or powders for topical administration; ophthalmic solutions or suspensions, i.e., eye drops, for administration to the eye; sprays or powder compositions for inhalation or intranasal administration; or creams, ointments, sprays, or suppositories for rectal or vaginal administration. Gelatin capsules contain the active ingredient and a powdered carrier, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc. Similar diluents can be used to prepare compressed tablets. Both tablets and capsules can be formulated as sustained-release products to provide sustained release of the drug over several hours. Compressed tablets can be coated with sugar or film to cover any unpleasant taste and protect the tablet from air, or can be enteric-coated for selective disintegration in the gastrointestinal tract. Liquid dosage forms for oral administration can include coloring agents and flavoring agents to increase patient acceptance. Generally speaking, water, suitable oil, saline, dextrose (glucose) aqueous solution and related sugar solution and glycols such as propylene glycol or polyethylene glycol are the carriers of suitable parenteral solutions. The solution for parenteral administration preferably includes a water-soluble salt of active ingredient, a suitable stabilizer and the buffer substance used as required. Antioxidant such as sodium bisulfite, sodium sulfite or ascorbic acid alone or in combination is a suitable stabilizer. Citric acid and its salt and sodium EDTA can also be used. In addition, parenteral solutions can also include preservatives, such as benzalkonium chloride, methylparaben or propylparaben and chlorobutanol.

[0045] For inhalation administration, compound of the present invention can be easily delivered in aerosol form from pressurized packaging or aerosol sprayer.The compound can also be delivered in the powder form prepared, and the powder composition can be sucked with the help of blowing into a powder inhaler device.The preferred delivery system for sucking is metered dose inhalation (MDI) aerosol, which can be formulated into a suspension or a solution of the compound of formula I in a suitable propellant, such as fluorocarbon or hydrocarbon.For eye administration, ophthalmic preparations can be prepared with a solution or a suspension of the appropriate weight percent of the compound of formula I in a suitable eye carrier, thereby keeping the compound in contact with the surface of the eye enough time so that the compound is infiltrated into the cornea and the inner area of ​​the eyes.

[0046] Useful pharmaceutical dosage forms for administering the compounds of the present invention include, but are not limited to, hard and soft gelatin capsules, tablets, parenteral injection solutions, and oral suspensions.

[0047] When the compounds of the present invention are administered stepwise or in combination with other therapeutic agents, the same dosage forms as described above may be used. When the drugs are administered in a physical combination, the dosage form and route of administration should be selected based on the compatibility of the combined drugs. The compounds of the present invention may be administered as the sole active ingredient or in combination with a second active ingredient, including those known to be useful in treating related diseases.

[0048] In a third aspect, the present invention provides a method for weight loss, muscle preservation, and muscle growth, comprising administering to an individual an effective amount of the aforementioned weight loss, muscle preservation, and muscle growth drug. The method can be used in vivo or in vitro. The individual can be a mammal, such as a human.

[0049] The weight-loss, muscle-preserving, and muscle-building drugs are unit dosage forms suitable for single administration of precise doses. 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 in the range of about 0.001 g / day to about 7 g / day. In other embodiments, the amount of the compound is in the range of about 0.002 g / day to about 6 g / day. In other embodiments, the amount of the compound is in the range of about 0.005 g / day to about 5 g / day. In other embodiments, the amount of the compound is in the range of about 0.01 g / day to about 5 g / day. In other embodiments, the amount of the compound is in the range of about 0.02 g / day to about 5 g / day. In other embodiments, the amount of the compound is in the range of about 0.05 g / day to about 2.5 g / day. In other embodiments, the amount of the compound is from about 0.1 g / day to about 1 g / day. In other embodiments, dosage levels below the lower limit of the above range may be sufficient. In other embodiments, dosage levels above the upper limit of the above range may 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.

[0050] The beneficial effects of the present invention are: The present invention provides a disulfide cyclic peptide compound for use in the preparation of drugs for weight loss, muscle preservation, and muscle growth. Animal experiments have shown that the compound with this structure can significantly reduce the weight of obese individuals, reduce food intake, reduce fat content, and increase lean meat content, thereby compensating for the muscle loss caused by current weight loss drugs and broadening the application field of the disulfide cyclic peptide compound. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 This is the weight result of mice on the 30th day of drug administration in Experiment 1.

[0052] Figure 2 This is the food intake result of mice on the 9th day of drug administration in Experiment 1.

[0053] Figure 3 This is the weight result of mice on the 30th day of drug administration in Experiment 2.

[0054] Figure 4 This is the food intake result of mice on the third day of drug administration in Experiment 2.

[0055] Figure 5 This is the result of the changes in muscle mass of mice on the 30th day of drug administration in Experiment 2.

[0056] Figure 6 This is a graph showing the changes in fat mass in mice on the 30th day of drug administration in Experiment 2. DETAILED DESCRIPTION

[0057] The following non-limiting examples are provided to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way. The following is merely an illustrative description of the scope of the present invention, and those skilled in the art may make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of protection claimed in this application.

[0058] The present invention will be further described below by way of specific examples. The various chemical reagents used in the examples of the present invention were obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all by weight. Unless otherwise specified, it is understood that the experiments were conducted at room temperature.

[0059] Terms and abbreviations:

[0060] QD: Once a day.

[0061] SC: subcutaneous injection.

[0062] PBS: phosphate-buffered saline.

[0063] Vehicle: control group.

[0064] Compound preparation: The following compounds were synthesized according to the methods described in the priority patent 202411230649.2 or Examples 1 to 7 in CN119462838A, respectively. Their structural characterizations were the same as those described in the priority patent 202411230649.2 or CN119462838A.

[0065] WP302-1: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2

[0066] WP302-2: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Pro-NH2

[0067] WP302-3: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Ile-NH2

[0068] WP302-4: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2

[0069] WP302-5: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2

[0070] WP302-6: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Pro-NH2

[0071] WP302-7: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2

[0072] The above compounds are used as experimental drugs, and their information is as follows:

[0073] Effect detection experiment 1: 1.1 Experimental Animals Experimental animals: DIO model male mice / SPF grade (Changzhou Cavens Laboratory Animal Co., Ltd., license number SYXK(Su)2022-0002), 20-22 weeks old, over 38 g.

[0074] The DIO mouse (Diet-Induced Obesity) is an animal model used to study obesity and diabetes. By selectively breeding mice with a susceptibility to obesity and diabetes, they develop obesity and diabetes on a high-fat diet. DIO mice are valuable for studying obesity, diabetes, and related metabolic diseases, helping to understand the pathogenesis of these diseases and develop new treatments. The DIO-B6 mouse is an obese mouse model (DIO) induced on a C57BL / 6 background strain using a 60% high-fat diet. These mice exhibit a phenotype characterized by weight gain, elevated random blood glucose levels, increased NK cells and macrophages, and elevated lipid profiles and liver function. They are useful for studying metabolic diseases such as obesity, diabetes, inflammation, and fatty liver disease, as well as for drug screening and preclinical efficacy evaluation.

[0075] Mouse strain: C57BL / 6J; Gender: male; High-fat feeding starting age: 5 weeks; High-fat feed: 60% high-fat feed (D12492).

[0076] The rearing conditions are as follows: Experimental animals were housed in an SPF-grade animal room at Suzhou Fangda Pharmaceutical Development Co., Ltd. The room was equipped with an air-conditioning system and good ventilation. The temperature was maintained between 20 and 26°C, and the humidity was maintained between 40% and 0%. Artificial lighting was used in the animal room, with a 12-hour light cycle and a 12-hour dark cycle (except when work lighting was required for experimental procedures or cleaning). Animals had free access to food and water. Animals were acclimated to the laboratory for at least 3 days before dosing. Animals were grouped based on their average body weight 2 days prior to dosing.

[0077] 1.2 Preparation of dosing solution: Accurately weigh an appropriate amount of compound, add a calculated volume of 1×PBS to completely dissolve the compound, stir thoroughly, and mix evenly to obtain a dosing solution.

[0078] 1.3 Administration

[0079] The weight was recorded before each day of administration and used to calculate the administration volume.

[0080] 1.4 Experimental Results The results are as follows Figure 1-Figure 2 The results showed that at a dose of 4 mg / kg, each compound exhibited different degrees of efficacy in reducing body weight and food intake.

[0081] Effect detection experiment 2: 2.1 Experimental Animals Experimental animals: Beijing Weitonglihua Laboratory Animal Technology Co., Ltd. (VRL): C57BL / 6J male mice, 15 weeks old.

[0082] The rearing conditions are as follows: Temperature: 20-26℃; Humidity: 40-70%; Photoperiod: 12 h (7:00 am - 7:00 pm); High-fat diet (HFD): Research Diets, D12492 (Protein: 20% Kcal. Fat: 60%. Kcal. Carbohydrate: 20% Kcal); Drinking water is pure water (used after high-pressure steam sterilization); During the feeding process, the rats were given free access to food and water.

[0083] The high-fat diet (HFD) induction period for this study lasted 16 weeks, and the efficacy experiment lasted 6 weeks. The efficacy experiment included a 1-week screening and baseline collection period (11 weeks after HFD induction) and a 5-week treatment period. All obese mice were randomly divided into groups based on baseline body weight and body fat content before dosing.

[0084] 2.2 Preparation of dosing solution: Solvent: PBS (Shanghai Shangbao Biotechnology Co., Ltd., T16551, 5012329), 0.01 M, pH 5.5.

[0085] Weigh an appropriate amount of compound powder, dissolve it in a solvent, and prepare a dosing solution of the desired concentration. Use ultrasound to assist dissolution. Prepare once every three days and store the prepared dosing solution at 2-8°C.

[0086] 2.3 Administration The experimental period was 36 days, with drug administration for 30 days. The grouping and drug administration were as follows:

[0087] 2.4 Experimental Results 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.

[0088] Rate of change calculation method: The data on the last day of drug administration is taken as the current value. After the model is successfully established, the data on day 0 (before drug administration) is taken as the baseline value.

[0089] The formula for calculating the relative baseline change rate is: Relative baseline change = (current value - baseline value) / baseline value × 100%.

[0090] The results are as follows Figure 3-Figure 6 The results showed that at a dose of 12 mg / kg, each compound exhibited varying degrees of weight loss and reduced food intake. More importantly, while losing weight, it also protected and increased muscle mass and reduced fat mass, compensating for the muscle loss caused by current weight loss drugs.

[0091] 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. The use of a disulfide cyclic peptide compound in the preparation of a drug for weight loss, muscle preservation, and muscle growth, characterized in that: The disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

2. The use according to claim 1, characterized in that R1 is Arg; R2 is acetyl or palmitoyl; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is amino; Furthermore, when R3 is absent, R2 is a palmitoyl group.

3. The use according to claim 1 or 2, characterized in that The disulfide cyclic peptide compound has the following structural formula: wherein R1, R2, R3 and R4 are as defined in claim 1 or 2.

4. The use according to claim 1, characterized in that R3 is selected from Ile, D-Phe, Pro or is missing, and R1 is Arg.

5. The use according to claim 1, characterized in that R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

6. The use according to claim 1, characterized in that When R3 is absent, R4 is a palmitoyl group.

7. The use according to any one of claims 1 to 6, characterized in that The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 8. The use according to claim 7, characterized in that The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 9. The use according to claim 8, characterized in that The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 10. A drug for losing weight, preserving muscle and increasing muscle mass, characterized in that: It comprises a disulfide cyclic peptide compound and a pharmaceutically acceptable carrier or excipient, wherein the disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

11. The drug for losing weight, preserving muscle and increasing muscle according to claim 10 or 11, characterized in that: R1 is Arg; R2 is acetyl or palmitoyl; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is amino; Furthermore, when R3 is absent, R2 is a palmitoyl group.

12. The drug for losing weight, preserving muscle and increasing muscle according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound has the following structural formula: wherein R1, R2, R3 and R4 are as defined in claim 10 or 11.

13. The drug for losing weight, preserving muscle and increasing muscle according to claim 10 or 11, characterized in that: R3 is selected from Ile, D-Phe, Pro or is missing, and R1 is Arg.

14. The drug for losing weight, preserving muscle and increasing muscle according to claim 10 or 11, characterized in that: R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

15. The drug for losing weight, preserving muscle and increasing muscle according to claim 10 or 11, characterized in that: When R3 is absent, R4 is a palmitoyl group.

16. The drug for losing weight, preserving muscle and increasing muscle according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 17. The drug for losing weight, preserving muscle and increasing muscle according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 18. The drug for losing weight, preserving muscle and increasing muscle mass according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。

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