Composition for preventing and treating children obesity and preparation method thereof
The composition prepared by combining sipuncula polypeptide and catalpol solves the safety and efficacy problems of existing childhood obesity drugs, and achieves safe and effective prevention and treatment of childhood obesity.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-02-27
- Publication Date
- 2026-04-10
AI Technical Summary
There is a lack of safe and effective drugs for preventing and treating childhood obesity in the current technology. Existing drugs have poor gastrointestinal tolerance, lack of fat-soluble vitamins, and potential risks of liver damage. Drugs developed on the market have been withdrawn due to serious side effects.
An oral formulation was prepared by combining Sipunculus tetrapods polypeptides with catalpol. The polypeptides were obtained by enzymatic hydrolysis of Sipunculus tetrapods and then mixed with catalpol to prepare a composition for preventing and treating childhood obesity, regulating intestinal flora balance, and improving metabolic disorders.
It effectively inhibits weight gain caused by a high-fat diet, lowers serum cholesterol and triglyceride levels, improves liver fat accumulation, alleviates fatty liver disease, and does not affect kidney function.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of medicine, and particularly relates to a composition for preventing and treating obesity in children and a preparation method thereof. BACKGROUND
[0002] Childhood obesity is becoming increasingly serious worldwide, especially in low- and middle-income countries such as the Pacific Islands. The China Residents Nutrition and Chronic Disease Report (2020) pointed out that the proportion of overweight and obesity among children under the age of 6 in China reached 10%, and the proportion of children and adolescents aged 6-17 years approached 20%. The prevalence of overweight and obesity among adult residents was 34.3% and 16.4%, respectively. Obesity-induced energy metabolism disorders not only affect the normal growth and development of children, but also increase the incidence and mortality of type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and certain cancers (such as breast cancer and liver cancer) in adulthood. Data shows that obese people live 7 years less than normal people, so childhood obesity has become a global public health concern.
[0003] Sipunculus nudus, commonly known as "sandworm", is an important marine biological resource. Recent studies have shown that bioactive peptides obtained by enzymatic hydrolysis of Sipunculus nudus have unique potential in metabolic regulation, providing a new source of natural substances for obesity prevention and treatment.
[0004] Catalpol is a natural iridoid glycoside widely found in Catalpa plants, and its anti-obesity pharmacological activity has been relatively clearly supported by modern pharmacological research.
[0005] Currently, only a few drugs such as orlistat are approved for the treatment of childhood obesity in clinical practice, and there are poor gastrointestinal tolerance, lack of fat-soluble vitamins, and potential risk of liver damage. More than 20 drugs developed in the past to prevent and treat childhood obesity by reducing energy intake or increasing energy consumption have mostly been withdrawn from the market due to serious side effects. Given the increasingly serious global epidemic of childhood obesity and the current lack of effective prevention and treatment measures, it is necessary to explore safe and more effective drugs for preventing and treating childhood obesity. Based on the above background, the present application first proposes a scientific combination of Sipunculus nudus polypeptide and catalpol, aiming to explore a more comprehensive and safer solution. SUMMARY
[0006] In order to overcome the shortcomings of the prior art, the first purpose of the present application is to provide a composition for preventing and treating obesity in children, which effectively improves obesity caused by high-fat feed.
[0007] The second purpose of the present application is to provide a preparation method of the composition for preventing and treating obesity in children, which is simple in process.
[0008] In order to achieve the above object, the technical scheme adopted by the present application is: The composition for preventing and treating obesity of children comprises the following raw materials in parts by weight: 35-45 parts of a pharmaceutical active ingredient, and 8-15 parts of an auxiliary material; the pharmaceutical active ingredient is composed of a polypeptide of Arenicola branchiatus and a catalpol in a mass ratio of 1: (1.5-3).
[0009] Further, the preparation method of the polypeptide of Arenicola branchiatus is as follows: The Arenicola branchiatus is cleaned, broken, and then added with water, chymotrypsin and trypsin for enzymolysis, centrifuged, and fractionated by an ultrafiltration membrane to prepare the polypeptide of Arenicola branchiatus.
[0010] Further, the added amount of water is 8-10 times of the mass of the Arenicola branchiatus; the added amount of chymotrypsin is 2000-2500 U / g, and the added amount of trypsin is 3500-4000 U / g.
[0011] Further, the cut-off molecular weight of the ultrafiltration membrane is 5 kDa and 10 kDa, respectively.
[0012] Further, the enzymolysis condition is that the pH is 7.5, the temperature is 45-50 DEG C, and the time is 3-4 h; the centrifugation condition is that the rotation speed is 10000-12000 rpm, the temperature is 4 DEG C, and the time is 15-20 min.
[0013] Further, the auxiliary material is composed of a lubricant and a disintegrant in a mass ratio of 1: (1.5-2.5).
[0014] Further, the lubricant is magnesium stearate, and the disintegrant is sodium carboxymethyl starch.
[0015] Further, the dosage form of the composition is an oral preparation.
[0016] Further, the oral preparation is a tablet.
[0017] The preparation method of the above composition for preventing and treating obesity of children comprises the following steps: The raw materials are weighed, the polypeptide of Arenicola branchiatus, the catalpol and the auxiliary material are mixed uniformly, and then the tablet is pressed.
[0018] Compared with the prior art, the present application has the following beneficial effects: This invention provides a composition for preventing and treating childhood obesity. Its active pharmaceutical ingredients are *Sipunculus nudus* polypeptide and catalpol, wherein catalpol effectively improves the internal environment of obesity-related metabolic disorders, while *Sipunculus nudus* polypeptide regulates the balance of beneficial intestinal flora, thereby improving intestinal function. When used together, these two ingredients can inhibit weight gain in mice on a high-fat diet, reduce serum total cholesterol, triglycerides, and low-density lipoprotein levels, and increase serum high-density lipoprotein levels. Furthermore, this composition can improve hepatic fat accumulation, alleviate fatty liver disease caused by it, and does not affect kidney function. Detailed Implementation
[0019] The technical solution of the present invention will be further described below with reference to specific embodiments. However, those skilled in the art should understand that the following embodiments are only for illustrating the present invention and should not be regarded as limiting the present invention. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the reagents or instruments used are all conventional products obtained through commercial channels.
[0020] Example 1 A polypeptide from the checkered sipuncula is prepared as follows: The Sipuntia spp. were cleaned and crushed. Water was added at a material-to-liquid ratio of 1:9. Then, chymotrypsin and trypsin were added at a concentration of 2200 U / g and 3700 U / g, respectively. Enzymatic hydrolysis was carried out at 47°C and pH 7.5 for 3.5 hours. The enzymes were then inactivated in a 90°C water bath for 10 minutes. After cooling, the centrifuge temperature was set to 4°C and the speed to 11000 rpm for 16 minutes to obtain the supernatant. The supernatant was then passed through ultrafiltration membranes with molecular weight cutoffs of 10 kDa and 5 kDa in a 4°C ice bath to obtain Sipuntia spp. polypeptides with a molecular weight of 5-10 kDa.
[0021] Example 2 A polypeptide from the checkered sipuncula is prepared as follows: Clean and crush the Sipunculus spp., add water at a material-to-liquid ratio of 1:8, then add chymotrypsin (2000 U / g) and trypsin (3500 U / g), and hydrolyze at 45℃ and pH 7.5 for 4 hours. Inactivate the enzymes in a 90℃ water bath for 10 minutes. After cooling, centrifuge at 4℃ and 10000 rpm for 20 minutes to obtain the supernatant. Under 4℃ ice bath conditions, pass the supernatant through ultrafiltration membranes with molecular weight cutoffs of 10 kDa and 5 kDa to obtain Sipunculus spp. polypeptides with molecular weights of 5-10 kDa.
[0022] Example 3 A polypeptide from the checkered sipuncula is prepared as follows: Clean and crush the Sipunculus spp., add water at a material-to-liquid ratio of 1:10, then add chymotrypsin (2500 U / g) and trypsin (4000 U / g). Enzymatically hydrolyze at 50°C and pH 7.5 for 3 hours, then inactivate the enzymes in a 90°C water bath for 10 minutes. After cooling, centrifuge at 4°C and 12000 rpm for 15 minutes to obtain the supernatant. Under 4°C ice bath conditions, pass the supernatant through ultrafiltration membranes with molecular weight cutoffs of 10 kDa and 5 kDa to obtain Sipunculus spp. polypeptides with molecular weights of 5-10 kDa.
[0023] Example 4 A polypeptide from the checkered sipuncula is prepared as follows: Clean and crush the Sipunculus spp., add water at a material-to-liquid ratio of 1:9, then add chymotrypsin (2200 U / g) and trypsin (3700 U / g). Enzymatically hydrolyze the mixture at 47°C and pH 7.5 for 3.5 hours, then inactivate the enzymes in a 90°C water bath for 10 minutes. After cooling, centrifuge at 4°C and 11000 rpm for 16 minutes to obtain the supernatant. Pass the supernatant through an ultrafiltration membrane with a molecular weight cutoff of 2 kDa at 4°C to obtain Sipunculus spp. polypeptides with a molecular weight of 0-2 kDa.
[0024] Example 5 A polypeptide from the checkered sipuncula is prepared as follows: The Sipuntia spp. were cleaned and crushed. Water was added at a material-to-liquid ratio of 1:9. Then, chymotrypsin and trypsin were added at a concentration of 2200 U / g and 3700 U / g, respectively. Enzymatic hydrolysis was carried out at 47°C and pH 7.5 for 3.5 hours. The enzymes were then inactivated in a 90°C water bath for 10 minutes. After cooling, the centrifuge temperature was set to 4°C and the speed to 11000 rpm for 16 minutes to obtain the supernatant. The supernatant was then passed through ultrafiltration membranes with molecular weight cutoffs of 20 kDa and 15 kDa in a 4°C ice bath to obtain Sipuntia spp. polypeptides with a molecular weight of 15-20 kDa.
[0025] Example 6 A composition for preventing and treating childhood obesity comprises the following raw materials in parts by weight: 39 parts of active pharmaceutical ingredient and 11 parts of excipients. The active pharmaceutical ingredient consists of *Sipunculus nudus* polypeptide and catalpol from Example 1 in a mass ratio of 1:2.5; the excipients consist of magnesium stearate and sodium carboxymethyl starch in a mass ratio of 1:2.
[0026] The preparation method of the above-mentioned composition for preventing and treating childhood obesity includes the following steps: Weigh out the raw materials, mix the sipuncula polypeptide, catalpol and sodium carboxymethyl starch at 10 rpm for 15 minutes, then add magnesium stearate and continue mixing for 5 minutes, controlling the hardness range to 65-75 N, and then compress into tablets.
[0027] Example 7 A composition for preventing and treating childhood obesity comprises the following raw materials in parts by weight: 35 parts of active pharmaceutical ingredient and 8 parts of excipients. The active pharmaceutical ingredient consists of *Sipunculus nudus* polypeptide and catalpol from Example 2 in a mass ratio of 1:1.5; the excipients consist of magnesium stearate and sodium carboxymethyl starch in a mass ratio of 1:1.5.
[0028] The preparation method of the above-mentioned composition for preventing and treating childhood obesity includes the following steps: Weigh out the raw materials, mix the sipuncula polypeptide, catalpol and sodium carboxymethyl starch at 15 rpm for 10 min, then add magnesium stearate and continue mixing for 5 min, controlling the hardness range to 65-75 N, and then compress into tablets.
[0029] Example 8 A composition for preventing and treating childhood obesity comprises the following raw materials in parts by weight: 45 parts of active pharmaceutical ingredient and 15 parts of excipients. The active pharmaceutical ingredient consists of *Sipunculus nudus* polypeptide and catalpol from Example 3 in a mass ratio of 1:3; the excipients consist of magnesium stearate and sodium carboxymethyl starch in a mass ratio of 1:2.5.
[0030] The preparation method of the above-mentioned composition for preventing and treating childhood obesity includes the following steps: Weigh out the raw materials, mix the sipuncula polypeptide, catalpol and sodium carboxymethyl starch at 12 rpm for 12 minutes, then add magnesium stearate and continue mixing for 5 minutes, controlling the hardness range to 65-75 N, and then compress into tablets.
[0031] Comparative Example 1 Based on Example 6, the Sipunculus peptide from Example 4 was used instead of the Sipunculus peptide from Example 2 to form Comparative Example 1.
[0032] Comparative Example 2 Based on Example 6, the Sipunculus peptide from Example 5 was used instead of the Sipunculus peptide from Example 2 to form Comparative Example 2.
[0033] Comparative Example 3 Based on Example 6, catalpol was omitted to form Comparative Example 3.
[0034] Experimental Example 1.1 Experimental Animals and Construction of Obesity Models Ninety C57BL / 6J mice, weighing 18-22g, were acclimatized for one week. Ten mice were randomly selected and fed a normal diet as a control group, while the remaining mice were fed a high-fat diet for 12 weeks. The high-fat diet consisted of 66.5% basal diet, 10% lard, 20% sucrose, and 1% cholesterol.
[0035] 1.2 Experimental grouping and drug administration Twelve weeks later, mice fed a high-fat diet were randomly assigned to groups and administered the drugs: Model group: administered an equal volume of physiological saline by gavage for 12 consecutive weeks; Positive control group: Orlistat was administered by gavage at a dose of 75 mg / kg / day for 12 consecutive weeks; Example 6 group: The composition of Example 6 was administered by gavage at a dose of 100 mg / kg / d of Sipunculus tetrapod polypeptide for 12 consecutive weeks; Example 7 group: The composition of Example 7 was administered by gavage at a dose of 100 mg / kg / d of Sipunculus tetrapod polypeptide for 12 consecutive weeks; Example 8 group: The composition of Example 8 was administered by gavage at a dose of 100 mg / kg / d of Sipunculus tetrapod polypeptide for 12 consecutive weeks; Comparative Example 1: The composition of Comparative Example 1 was administered by gavage at a dose of 100 mg / kg / d of Sipunculus nudus peptide for 12 consecutive weeks. Comparative Example 2: The composition of Comparative Example 2 was administered by gavage at a dose of 100 mg / kg / d of Sipunculus nudus peptide for 12 consecutive weeks. Comparative Example 3: The drug of Comparative Example 3 was administered by gavage at a dose of 100 mg / kg / d of Sipunculus nudus pv. 3 for 12 consecutive weeks. Normal control group: administered an equal volume of physiological saline by gavage for 12 consecutive weeks.
[0036] 1.3 Detection Indicators 1.3.1 Weight The average body weight of mice in each group after the last administration was recorded, and the results are shown in Table 1.
[0037] 1.3.2 Blood lipid profile (four tests) and liver and kidney function tests After fasting for 12 hours following the last administration, blood was collected from the orbital cavity, centrifuged, and serum was separated. The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), liver function indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and kidney function indicators creatinine (Cr) and blood urea nitrogen (BUN) were measured in the serum. The results are shown in Table 2-3.
[0038] 1.3.3 Fat content After blood collection, the mice were anesthetized and euthanized. The weights of inguinal white fat (iWAT), epididymal white fat (eWAT), and liver fat were weighed. The results are shown in Table 4.
[0039] Table 1 Table 2 Table 3 Table 4 Table 1 shows that the body weight of mice in the model group was significantly increased compared to the normal control group, indicating that the obesity model was successfully established. Compared to the model group, the body weight of mice in Examples 6-8 and Comparative Examples 1-3 was reduced, with the reduction being particularly significant in Examples 6-8. These results demonstrate that the composition obtained in this invention can effectively improve obesity induced by a high-fat diet.
[0040] Table 2 shows that, compared with the normal control group, the serum levels of TC, TG, and LDL-C in the model group mice increased, while the HDL-C level decreased. Compared with the model group, the serum levels of TC, TG, and LDL-C in Examples 6-8 and Comparative Examples 1-3 mice decreased, while the HDL-C level increased, with the increase being particularly significant in Examples 6-8. These results indicate that the composition obtained in this invention can effectively improve lipid metabolism.
[0041] Table 3 shows that, compared with the normal control group, the serum AST and ALT levels of mice in the model group were increased. Compared with the model group, the serum AST and ALT levels of mice in Examples 6-8 and Comparative Examples 1-3 were decreased, with the decrease being particularly significant in Examples 6-8. These results indicate that the composition obtained in this invention can effectively improve fatty liver lesions caused by lipid metabolism disorders. Compared with the normal control group, there were no significant differences in serum Cr and BUN levels in the model group, Examples 6-8, and Comparative Examples 1-3. These results indicate that the composition obtained in this invention does not affect renal function.
[0042] As shown in Table 4, compared with the normal control group, the iWAT, eWAT, and liver fat content of mice in the model group were all increased. Compared with the model group, the iWAT, eWAT, and liver fat content of mice in Examples 6-8 and Comparative Examples 1-3 were all decreased, with the decrease being particularly significant in Examples 6-8. These results demonstrate that the composition obtained in this invention can effectively reduce fat content.
[0043] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.
Claims
1. A composition for preventing and treating childhood obesity, characterized in that, The raw materials include the following parts by weight: 35-45 parts of active pharmaceutical ingredient and 8-15 parts of excipients; the active pharmaceutical ingredient is composed of tetrahydropalmatus polypeptide and catalpol in a mass ratio of 1:(1.5-3).
2. The composition for preventing and treating childhood obesity as described in claim 1, characterized in that, The preparation method of the square-patterned sipuncula polypeptide is as follows: The Sipuntia lataniae were cleaned, crushed, and then enzymatically hydrolyzed with water, chymotrypsin, and trypsin. After centrifugation and ultrafiltration, the Sipuntia lataniae polypeptide was obtained.
3. The composition for preventing and treating childhood obesity as described in claim 2, characterized in that, The amount of water added is 8-10 times the mass of the Sipunculus nudus; the amount of chymotrypsin added is 2000-2500 U / g, and the amount of trypsin added is 3500-4000 U / g.
4. The composition for preventing and treating childhood obesity as described in claim 2, characterized in that, The ultrafiltration membranes have molecular weight cutoffs of 5 kDa and 10 kDa, respectively.
5. The composition for preventing and treating childhood obesity as described in claim 2, characterized in that, The enzymatic hydrolysis conditions are: pH 7.5, temperature 45-50℃, and time 3-4h; the centrifugation conditions are: speed 10000-12000rpm, temperature 4℃, and time 15-20min.
6. The composition for preventing and treating childhood obesity as described in claim 1, characterized in that, The excipients consist of a lubricant and a disintegrant in a mass ratio of 1:(1.5-2.5).
7. The composition for preventing and treating childhood obesity as described in claim 6, characterized in that, The lubricant is magnesium stearate, and the disintegrant is sodium carboxymethyl starch.
8. The composition for preventing and treating childhood obesity as described in claim 1, characterized in that, The composition is in the form of an oral preparation.
9. The composition for preventing and treating childhood obesity as described in claim 8, characterized in that, The oral preparation is a tablet.
10. A method for preparing the composition for preventing and treating childhood obesity according to any one of claims 1-9, characterized in that, Includes the following steps: Weigh out all the raw materials, mix the Stardust cricket polypeptide, catalpol and excipients evenly, compress into tablets, and it is ready.