Amino acid cross-linked polysaccharide polymer, hydrogel and preparation method thereof

Abstract

The invention relates to an amino acid cross-linked polysaccharide polymer, hydrogel and a preparation method thereof. The cross-linked polysaccharide polymer is formed by cross-linking a component A and a component B, wherein the component A is polysaccharide or a polysaccharide derivative; the component B is a substance with strong polar groups, and the strong polar groups comprise at least one amino group and one carboxyl group. The polymer has a stable three-dimensional rigid network structure, has relatively strong swelling property, can play a role in greatly enhancing mechanical strength / elastic modulus, has no irritation to digestive tract mucosa, and is easy to degrade.

Description

Amino acid cross-linked polysaccharide polymer, hydrogel and preparation method thereof

[0001] This application claims priority to the prior application with patent application number 2023112929130 filed with the State Intellectual Property Office of China on October 8, 2023, and invention name “A kind of amino acid cross-linked polysaccharide polymer, hydrogel and preparation method thereof”. Technical Field

[0002] The invention belongs to the field of polymers, and in particular relates to an amino acid cross-linked polysaccharide polymer, a hydrogel and a preparation method thereof. Background Art

[0003] Polymers formed by crosslinking polysaccharides are crosslinked hydrophilic polymers capable of absorbing and retaining large amounts of water. The crosslinks between the polymer chains form a network that ensures the structural integrity of the hydrogel, allowing the aqueous phase to be retained within the molecular grid, causing the hydrogel to swell a certain amount in volume and mass during this process. Prior patents, including CN201280036565.4 and CN201680011075.7, have successfully prepared water-absorbent polymer hydrogels by crosslinking water-soluble cellulose derivatives with polycarboxylic acids. This preparation process involves selecting an appropriate heat treatment temperature and time to form the crosslinked polymer. However, these polymer hydrogels are often prepared through esterification crosslinking, resulting in insufficient crosslinking strength, unsatisfactory swelling properties and mechanical strength, and poor user experience. Swelling properties determine the volume expansion multiple, while mechanical properties determine stability and durability. Therefore, there is a need to develop new polymer hydrogels containing non-toxic crosslinking agents that can improve swelling properties and / or mechanical properties.

[0004] Summary of the Invention

[0005] In order to improve the above technical problems, the present invention relates to an amino acid cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof, a hydrogel comprising the polymer or a pharmaceutically acceptable salt thereof, and a method for forming the polymer.

[0006] The technical solutions of the present invention are as follows:

[0007] A cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof, wherein the cross-linked polysaccharide polymer is formed by cross-linking component A and component B, wherein:

[0008] The component A is a polysaccharide or a polysaccharide derivative, which can be selected from at least one of the following substances: cellulose or its derivatives, alginic acid or its derivatives, starch or its derivatives, pectin or its derivatives, heparin or its derivatives, hyaluronic acid or its derivatives, chondroitin or its derivatives, chitosan or its derivatives, etc.;

[0009] The component B is a substance having a strong polar group, and the strong polar group includes at least one amino group and at least one carboxyl group.

[0010] According to an embodiment of the present invention, the cellulose may be at least one selected from carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and the like.

[0011] According to an embodiment of the present invention, the cellulose derivative may be selected from cellulose salts, preferably alkali metal salts of cellulose, such as at least one of sodium carboxymethyl cellulose, potassium carboxymethyl cellulose, sodium carboxyethyl cellulose and potassium carboxyethyl cellulose.

[0012] According to an embodiment of the present invention, the alginic acid derivative can be selected from alginates, preferably alkali metal salts of alginic acid, specifically at least one of sodium alginate and potassium alginate.

[0013] According to an embodiment of the present invention, the component A is preferably carboxymethyl cellulose or a salt thereof, more preferably sodium carboxymethyl cellulose.

[0014] According to an embodiment of the present invention, the strongly polar group may include 1, 2, 3 or more amino groups.

[0015] According to an embodiment of the present invention, the strongly polar group may include 1, 2, 3 or more carboxyl groups.

[0016] According to an embodiment of the present invention, the component B is an amino acid, preferably at least one of alanine, glutamic acid, isoleucine, leucine, valine, asparagine, glutamine and lysine, and the above amino acids include L configuration and D configuration.

[0017] According to an embodiment of the present invention, the amino acid is preferably an L-configuration amino acid, such as at least one of L-alanine, L-glutamic acid, L-glutamine and L-asparagine.

[0018] According to an embodiment of the present invention, the component B is preferably L-alanine.

[0019] According to an embodiment of the present invention, the cross-linked polysaccharide polymer has a three-dimensional rigid network structure, which is formed by an amidation reaction between the amino group of component B and the carboxyl group of component A, and an esterification reaction between the carboxyl group of component B and the hydroxyl group of component A. The three-dimensional rigid network structure is the skeleton of the cross-linked polysaccharide polymer.

[0020] According to an embodiment of the present invention, the swelling ratio of the cross-linked polysaccharide polymer in water is not less than 80 times, for example not less than 90 times, and further for example not less than 100 times.

[0021] According to an embodiment of the present invention, the weight average molecular weight of component A is 20,000-2,000,000 Da, preferably 50,000-1,000,000 Da, for example, 50,000 Da, 100,000 Da, 150,000 Da, 200,000 Da, 250,000 Da, 300,000 Da, 350,000 Da, 400,000 Da, 450,000 Da, 500,000 Da, 550,000 Da, 600,000 Da, 650,000 Da, 700,000 Da, 750,000 Da, 800,000 Da, 850,000 Da, 900,000 Da, 950,000 Da or 1,000,000 Da.

[0022] According to an embodiment of the present invention, the viscosity of component A in a 1 wt% aqueous solution at 25° C. (unit: mPa.s) is 20-8000, preferably 100-4000, for example, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900 or 4000.

[0023] According to an embodiment of the present invention, the degree of substitution of the polysaccharide derivative is 0.1-2.5, for example, it can be 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4 or 2.5. Taking cellulose as an example, the degree of substitution of a cellulose derivative refers to the amount of substance that replaces the active hydroxyl groups on each D-glucose unit of cellulose; for example, CMC-Na-0.9 means that 0.9 active hydroxyl groups on each D-glucose unit of carboxymethyl cellulose are replaced by sodium ions, that is, the degree of substitution of sodium carboxymethyl cellulose is 0.9.

[0024] According to an embodiment of the present invention, the component B (amino acid) acts as a cross-linking agent.

[0025] According to an embodiment of the present invention, the mass ratio of component A to component B is 50-99:50-1, for example, it can be 99:1, 98:2, 97:3, 96:4, 95:5, 94:6, 93:7, 92:8, 91:9, 90:10, 88:12, 85:15, 80:20, 75:25, 70:30, 65:35, 60:40, 55:45 or 50:50.

[0026] The present invention also provides a method for preparing the cross-linked polysaccharide polymer, comprising the following steps: mixing the component A, the component B and water, and obtaining the cross-linked polysaccharide polymer through a cross-linking reaction;

[0027] Preferably, the mass ratio of component A to water is greater than 30; in some embodiments, the mass ratio of component A to water is greater than 30 and not more than 50, for example, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45 or 50.

[0028] According to an embodiment of the present invention, the preparation method further comprises a drying step.

[0029] According to one embodiment of the present invention, component B and water may be prepared into solution B, component A and water may be prepared into solution A, and the solution A and the solution B may be mixed under stirring;

[0030] Preferably, in the mixing step, the solution B is added to the solution A under stirring conditions and the mixing is continued;

[0031] Preferably, in the solution A, the mass ratio of the component A to water is 1-20, preferably 2-10.

[0032] According to an embodiment of the present invention, the mixing is stirring mixing, for example, stirring at 20-50° C. for at least 30 minutes.

[0033] According to an embodiment of the present invention, the temperature of the cross-linking reaction is 60-150°C, such as 80-140°C, preferably 90-130°C, and exemplified by 100°C, 110°C, 120°C, 125°C, and 135°C.

[0034] According to an embodiment of the present invention, the cross-linking reaction time is 1-8 hours, such as 1-5 hours, preferably 2-5 hours, and more preferably 3-4 hours.

[0035] According to an embodiment of the present invention, the drying temperature is 10-100°C, preferably 30-90°C, more preferably 40-80°C, and exemplified by 50°C, 60°C, 70°C, 75°C, 85°C, and 95°C.

[0036] According to an embodiment of the present invention, the drying time is 0.2-6 hours, such as 0.5-4 hours, preferably 0.5-3 hours, more preferably 1-2 hours. Preferably, the cross-linked polysaccharide polymer is dried until the moisture content is less than 10%, such as less than 8%.

[0037] According to an embodiment of the present invention, the preparation method comprises the following steps:

[0038] Mixing the component A, component B and water, performing a cross-linking reaction, and drying to obtain the cross-linked polysaccharide polymer;

[0039] The mass ratio of component A to component B is 90-99:1-10, and the mass ratio of component A to water is greater than 30;

[0040] The cross-linking reaction temperature is 120-140°C and the time is 2-5h;

[0041] The drying temperature is 70-90°C and the drying time is 0.5-3h;

[0042] In some embodiments, the component A is sodium carboxymethylcellulose, and the component B is L-alanine.

[0043] According to an embodiment of the present invention, the water is deionized water.

[0044] The present invention also provides a hydrogel formed by swelling the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof in water.

[0045] According to an embodiment of the present invention, the swelling ratio of the cross-linked polysaccharide polymer in water is ≥30 times, preferably greater than 60 times, and further preferably greater than 80 times.

[0046] The present invention also provides a composition comprising the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof, or the hydrogel.

[0047] According to an embodiment of the present invention, the composition may further include an adjuvant, preferably a pharmaceutically acceptable adjuvant. For example, the adjuvant includes an additive, and the additive includes but is not limited to at least one of a preservative, a solubilizer / surfactant, a buffer, an isotonicity adjusting agent, a suspending agent, a dispersant, a wetting agent, and the like.

[0048] The present invention also provides a pharmaceutical preparation comprising the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof, or a hydrogel; or prepared from the above composition.

[0049] The present invention also provides use of the cross-linked polysaccharide polymer or its pharmaceutically acceptable salt, hydrogel or the above composition in preparing a pharmaceutical preparation.

[0050] According to an embodiment of the present invention, the form of the pharmaceutical preparation includes but is not limited to tablets, capsules, powders, granules, syrups, gels, suspensions, dispersible tablets, chewable tablets, effervescent tablets, capsules, granules, sustained-release preparations, etc.

[0051] According to an embodiment of the present invention, the pharmaceutical preparation is used to prevent and / or treat overweight and related diseases, such as overweight, obesity, prediabetes, diabetes, high blood cholesterol, hypertension, cardiovascular and cerebrovascular diseases, constipation, osteoarthritis, gout, sleep apnea syndrome, infertility, menstrual disorders, abnormal ovulation and / or abnormal hormone levels.

[0052] The present invention also provides a method for preventing and / or treating overweight and related diseases, comprising administering the above-mentioned pharmaceutical preparation to a subject in need thereof;

[0053] For example, the overweight and related diseases include overweight, obesity, prediabetes, diabetes, high blood cholesterol, hypertension, cardiovascular and cerebrovascular diseases, constipation, osteoarthritis, gout, sleep apnea syndrome, infertility, menstrual disorders, abnormal ovulation and / or abnormal hormone levels.

[0054] The present invention also provides a product comprising the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt, hydrogel or composition thereof.

[0055] The present invention also provides use of the cross-linked polysaccharide polymer or its pharmaceutically acceptable salt, hydrogel or the above composition in preparing products.

[0056] According to an embodiment of the present invention, the product can be a medicine, a pharmaceutical excipient, a medical device, a food, a food additive, a dietary supplement, a health product, a meal replacement, a dietary supplement, etc.

[0057] According to an embodiment of the present invention, the product can be used for health management and / or diet control, including weight loss, weight management, reducing calorie intake, reducing appetite and / or promoting satiety, etc.

[0058] The present invention also provides a method for health management and / or diet control, comprising administering the above-mentioned preparation to a subject in need thereof;

[0059] For example, the health management and / or diet control includes losing weight, managing weight, reducing calorie intake, reducing appetite and / or promoting satiety, etc.

[0060] According to an embodiment of the present invention, the pharmaceutical preparation or product is taken 10-60 minutes before a meal (e.g., 10, 20, 30, 40, 50, 60 minutes before a meal), preferably a certain amount is taken between 30-60 minutes before a meal (e.g., 30, 40, 50, 60 minutes before a meal).

[0061] According to an embodiment of the present invention, the pharmaceutical preparation or product can be taken once a day, twice a day, three times a day or more times a day, preferably three times a day, and preferably 30 to 60 minutes before three meals a day.

[0062] According to an embodiment of the present invention, the dosage of the pharmaceutical preparation or product is a predetermined amount of a cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof, or a hydrogel, calculated to produce the desired therapeutic effect in combination with the desired carrier. Medical technicians in this field can determine the therapeutically effective amount based on subject (e.g., patient) characteristics well known in the art, such as age, weight, sex, symptoms, complications, other diseases, etc.

[0063] In the present invention, "at least one" means one, two, three or more; "at least one" means one, two, three or more. Beneficial effects

[0064] (1) The cross-linked polysaccharide polymer provided by the present invention uses a substance with a strong polar group (i.e., component B) as a cross-linking agent. Compared with polymers or hydrogels cross-linked by esterification reaction alone, it can form a more stable three-dimensional rigid network structure, which serves as a skeleton to support the cross-linked polysaccharide. The structure has a large spatial network and steric hindrance, which can not only store water molecules in the network structure and have strong swelling properties, but also greatly enhance the mechanical strength / elastic modulus. As a result, it has obvious performance advantages in mechanical strength and medium uptake rate compared with hydrogels known in the prior art, thereby increasing the actual duration and effect of the polymer at the target location.

[0065] (2) The present invention uses a non-toxic cross-linking agent to synthesize the polymer without using a catalyst, eliminating the problem of low yield due to the presence of residual catalyst or the need to remove the residual catalyst.

[0066] (3) The polymer or hydrogel described in the present invention has good biocompatibility, is non-irritating to the digestive tract mucosa, can be well degraded in the body, is highly safe, and can significantly reduce weight in both animals and humans after administration.

[0067] (4) The product obtained by the present invention has strong swelling properties by optimizing the preparation process, such as cross-linking time. DETAILED DESCRIPTION

[0068] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0069] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0070] Unless otherwise specified, the degree of substitution of CMC-Na used in the following examples is 0.9, and unless otherwise specified, the molecular weight of CMC-Na used is 1,000,000 Da.

[0071] Example 1 Preparation of Alanine Cross-linked Sodium Carboxymethyl Cellulose Polymer

[0072] formula:

[0073] Preparation steps:

[0074] 1. Dissolve 0.2 g of L-alanine in 20 ml of deionized water and stir with a magnetic stirrer until completely dissolved to obtain Solution B.

[0075] 2. Add 4.8 g of CMC-Na-0.9 to 130 ml of deionized water and stir at 60 rpm for 2 h to obtain solution A. Add solution B to solution A and continue stirring in a constant temperature oil bath at 40°C for 1 h.

[0076] 3. After complete dissolution, connect the reflux device to the flask and place it in an oil bath at 130°C for 3 hours. Then take it out, filter the reactant, wash it with deionized water 3 times, and dry it at 80°C for 1 hour to obtain the final polymer.

[0077] Comparative Example 1 Preparation of Citric Acid Cross-linked Sodium Carboxymethyl Cellulose Polymer

[0078] formula:

[0079] Preparation steps:

[0080] 1. Dissolve 0.2 g of citric acid in 20 ml of deionized water and stir with a magnetic stirrer until completely dissolved to obtain solution B.

[0081] 2. Add 4.8 g of CMC-Na-0.9 to 130 ml of deionized water and stir at 60 rpm for 2 h to obtain solution A. Add solution B to solution A and continue stirring in a constant temperature oil bath at 40°C for 1 h.

[0082] 3. After complete dissolution, connect the reflux device to the flask and place it in an oil bath at 130°C for 3 hours. Then take it out, filter the reactants, wash them with deionized water 3 times, and dry them at 80°C for 1 hour to obtain the final polymer.

[0083] Test Example 1

[0084] (1) Performance test method

[0085] 1. Swelling rate

[0086] a) Prepare standard simulated gastric fluid (SGF) by mixing 7 mL of 37% HCl, 2 g of NaCl, and 3.2 g of pepsin in deionized water. Prepare diluted SGF (Di-SGF) by mixing 1 part SGF with 8 parts deionized water.

[0087] b) Place a dry glass funnel on a stand and pour 40 g of purified water into the funnel. Once no further drops of liquid are detected at the neck of the funnel (approximately 5 minutes), place the funnel in a dry, empty glass beaker (Beaker #1) and place the beaker on a tared scale to record the weight of the empty apparatus (W1). Prepare 40 g of Di-SGF solution as described above and place it in Beaker #2. Using weighing paper, accurately weigh 0.25 g of the polymer powder sample. Add the polymer powder sample to Beaker #2 and gently stir with a magnetic stirrer for 30 minutes without creating a vortex. Remove the stirring bar from the resulting suspension, place the funnel on a stand, and pour the suspension into the funnel, allowing the material to drain for 10 ± 1 minutes. Place the funnel containing the drained material in Beaker #1 and weigh it (W2). The swelling ratio is calculated according to the following formula: Swelling ratio = (W2 - W1) / 0.25. The assay was performed in triplicate.

[0088] 2. Residual rate in simulated gastric volume in vitro

[0089] (1) Injection: single dose (2.25 g polymer powder sample) + 450 mL water + 250 g food;

[0090] (2) Dissolution medium: simulated gastric fluid (2010 Chinese Pharmacopoeia formula)

[0091] (3) Test method: continuous experiment (n=1)

[0092] (4) Test duration: 4 hours

[0093] (5) Sampling: Collect gastric residue after 4 hours;

[0094] (6) Parameter determination:

[0095] a) Weigh the mass m2 of the gastric residue collected 4 hours later;

[0096] b) Picture record of the appearance of gastric residue after completion;

[0097] c) Gastric occupancy rate = m2 / (total gastric intake mass) × 100%.

[0098] This test focuses on gastric digestion and does not involve intestinal digestion.

[0099] The above polymer powder samples are the polymer powders in Examples and Comparative Examples.

[0100] (2) Performance test results

[0101] The performance test results are shown in Table 1.

[0102] Table 1

[0103] After testing, the polymer of Example 1 has a good swelling rate and in vitro simulated gastric volume retention rate, both of which far exceed those of Comparative Example 1. That is, the sodium carboxymethyl cellulose cross-linked by amidation reaction has better water absorption performance and longer gastric space occupation time than the polymer formed by cross-linking sodium carboxymethyl cellulose using only esterification reaction.

[0104] The polymer of Example 1 has been proven to have good biocompatibility through experiments, is non-irritating to the digestive tract mucosa, can be well degraded in the body, is highly safe and non-toxic, and can significantly reduce weight in both animals and humans after administration.

[0105] Examples 2-6

[0106] The raw material formulas of Examples 2-6 are as follows, and the corresponding polymers are prepared according to the reaction conditions of Example 1. The swelling ratio of each polymer was measured according to the swelling ratio test method as described above, and the results are shown in Table 2.

[0107] Table 2

[0108] Examples 7-11

[0109] Based on the preparation process of Example 1, the effects of various process parameters, such as different molecular weights of CMC-Na, different drying times, and different crosslinking times, on the product swelling performance were investigated by adjusting certain parameters. The swelling performance was tested according to the swelling test method described above, as shown in Table 3.

[0110] Table 3

[0111] Examples 12-18

[0112] Based on the preparation process of Example 1, the effects of different raw material ratios on the product's swelling performance were investigated by adjusting certain parameters. Other parameters remained the same as in Example 1, and the swelling performance was tested according to the swelling test method described above. As shown in Table 4, when the mass ratio of CMC-Na to L-alanine was (96-98):(2-4), and the mass ratio of water to CMC-Na was above 30, the swelling ratio could reach over 100 times.

[0113] Table 4

[0114] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof, characterized in that: The cross-linked polysaccharide polymer is formed by cross-linking component A and component B, wherein: The component A is a polysaccharide or a polysaccharide derivative; The component B is a substance having a strong polar group, and the strong polar group includes at least one amino group and at least one carboxyl group.

2. The cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The component A is selected from at least one of the following substances: cellulose or its derivatives, alginate or its derivatives, starch or its derivatives, pectin or its derivatives, heparin or its derivatives, hyaluronic acid or its derivatives, chondroitin or its derivatives, chitosan or its derivatives; And / or, the component B is an amino acid, preferably at least one of alanine, glutamic acid, isoleucine, leucine, valine, asparagine, glutamine and lysine, and the amino acid includes L configuration and D configuration; Preferably, the component B is an L-configuration amino acid; Preferably, the weight average molecular weight of component A is 20,000-2 million Da, preferably 50,000-1 million Da; Preferably, the degree of substitution of the polysaccharide derivative is 0.1-2.5; Preferably, the mass ratio of component A to component B is 50-99:50-1.

3. The cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The cellulose is selected from at least one of carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose; The cellulose derivative is selected from cellulose salts, preferably alkali metal salts of cellulose, such as at least one of sodium carboxymethyl cellulose, potassium carboxymethyl cellulose, sodium carboxyethyl cellulose and potassium carboxyethyl cellulose; The alginic acid derivative is selected from alginates, preferably alkali metal salts of alginic acid, such as at least one of sodium alginate and potassium alginate.

4. The cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, characterized in that: The cross-linked polysaccharide polymer has a three-dimensional rigid network structure, which is formed by an amidation reaction between the amino group of component B and the carboxyl group of component A, and an esterification reaction between the carboxyl group of component B and the hydroxyl group of component A. The three-dimensional rigid network structure is the skeleton of the cross-linked polysaccharide polymer.

5. The method for preparing the cross-linked polysaccharide polymer according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: mixing the component A, the component B and water, and obtaining the cross-linked polysaccharide polymer through a cross-linking reaction; Preferably, the mass ratio of component A to water is greater than 30; Preferably, the preparation method further comprises a drying step.

6. The preparation method according to claim 5, characterized in that: The temperature of the cross-linking reaction is 60-150° C., and the time of the cross-linking reaction is 1-8 hours; And / or, the drying temperature is 10-100° C., and the drying time is 0.2-6 h.

7. A hydrogel, characterized in that: The hydrogel is formed by swelling the cross-linked polysaccharide polymer or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 4 in water.

8. A composition, characterized in that The composition comprises the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, or comprises the hydrogel according to claim 7.

9. A pharmaceutical preparation, characterized in that The pharmaceutical preparation comprises the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, or the hydrogel according to claim 7; or is prepared from the composition according to claim 8; Preferably, the pharmaceutical preparation is used to prevent and / or treat overweight and related diseases, such as overweight, obesity, prediabetes, diabetes, hypercholesterolemia, hypertension, cardiovascular and cerebrovascular diseases, constipation, osteoarthritis, gout, sleep apnea syndrome, infertility, menstrual disorders, abnormal ovulation and / or abnormal hormone levels.

10. A product comprising the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, the hydrogel according to claim 7, or the composition according to claim 8; Preferably, the product is a medicine, a pharmaceutical excipient, a medical device, a food, a food additive, a dietary supplement, a health product, a meal replacement or a dietary supplement; Preferably, the product is used for health management and / or diet control, including weight loss, weight management, reducing calorie intake, reducing appetite and / or promoting satiety.

11. Use of the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, the hydrogel according to claim 7 or the composition according to claim 8 in the preparation of a pharmaceutical preparation; Preferably, the pharmaceutical preparation is the pharmaceutical preparation according to claim 9.

12. Use of the cross-linked polysaccharide polymer or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, the hydrogel according to claim 7 or the composition according to claim 8 in the preparation of a product; Preferably, the article is the article according to claim 10.

13. A method for preventing and / or treating overweight and related diseases, comprising administering the pharmaceutical preparation of claim 9 to a subject in need thereof; Preferably, the overweight and related diseases include overweight, obesity, prediabetes, diabetes, Cholesterol, hypertension, cardiovascular and cerebrovascular diseases, constipation, osteoarthritis, gout, sleep apnea syndrome, infertility, menstrual disorders, abnormal ovulation and / or abnormal hormone levels, etc.

14. A method of health management and / or diet control, comprising administering the preparation of claim 10 to a subject in need thereof; Preferably, the health management and / or diet control includes slimming, weight management, reducing calorie intake, reducing appetite and / or promoting satiety, etc.