Polymer hydrogel for weight management and preparation method thereof

Abstract

The invention discloses a polymer hydrogel for weight management and a preparation method thereof, and belongs to the technical field of hydrogel preparation. The preparation method of the polymer hydrogel comprises the following steps: dissolving a polymer derivative and dicarboxylic acid in a solvent to obtain a mixed solution; adding a cellulose polymer into the mixed solution, mixing, and drying to obtain a particle material; and carrying out esterification cross-linking reaction on the particle material to obtain the polymer hydrogel, the polymer derivative comprises recombinant collagen and / or an amino acid polymer. According to the invention, a polymer derivative and dicarboxylic acid are used as cross-linking agents, a cellulose polymer is used as a substrate, chemical cross-linking reaction is carried out at a certain temperature to form a double-cross-linked network structure, and the edible polymer hydrogel with high swelling degree and high strength is obtained.

Description

Technical Field

[0001] The present invention belongs to the technical field of hydrogel preparation, and more specifically relates to a polymer hydrogel for weight management and a preparation method thereof. Background Art

[0002] Obesity is a major health challenge faced today. Overweight and obesity can have a serious impact on health. Overweight and obesity are important causes of prediabetes and type 2 diabetes mellitus (T2DM); obese patients are at increased risk of often suffering from hyperlipidemia and hypertension; overweight and obesity are prone to cause obstructive sleep apnea syndrome, metabolic reproductive endocrine diseases, etc.; in addition, obesity is an independent risk factor for cardiovascular diseases.

[0003] The main weight loss methods for overweight and obese patients are as follows: (1) A diet weight loss method of continuously ingesting no more than 1400 kcal of calories per day for a long time, which is usually difficult to adhere to for a long time; (2) Exercise weight loss, which requires excessive or even maximal exercise. Moreover, excessive exercise has a huge impact on the body's bones, joints and muscles and can cause irreversible joint damage to the joints; (3) Drug weight loss. Although several drugs have been approved for marketing in China, their side effects need to be carefully considered; (4) Gastrointestinal surgery for weight loss. Although such surgical weight loss has good effects, it also has relatively high risks, and 98-99% of people refuse surgical operations.

[0004] In recent years, a method of weight loss by edible polymer hydrogels has emerged in the weight loss market. After being taken in the stomach, the hydrogel will absorb water and swell, increasing the volume of the stomach contents and reducing the food intake of the human body to achieve the purpose of weight loss. However, since the raw materials mostly use cellulose substances, they do not provide energy, and long-term use is likely to cause malnutrition. Therefore, an edible hydrogel that can provide energy for the body has emerged as the times require. However, the existing edible hydrogels that can provide energy for the body have poor swelling degree and strength and cannot meet the application requirements of higher requirements for edible hydrogels. Therefore, it is of great significance to develop an edible hydrogel that can provide energy for the body and has excellent swelling degree and strength. Summary of the Invention

[0005] The purpose of the present invention is to provide a polymer hydrogel for weight management and a preparation method thereof to solve the problems existing in the above-mentioned prior art and realize the preparation of an edible hydrogel that can provide energy for the body and has excellent swelling degree and strength.

[0006] To achieve the above purpose, the present invention provides the following solutions:

[0007] One of the technical solutions of the present invention: Provide a preparation method of a polymer hydrogel for weight management, including the following steps:

[0008] Dissolve the polymer derivative and the dicarboxylic acid in a solvent to obtain a mixed solution;

[0009] Add a cellulose-based polymer to the mixed solution, mix, and then dry to obtain granular materials;

[0010] Perform an esterification cross-linking reaction on the granular materials to obtain the polymer hydrogel;

[0011] The polymer derivative includes recombinant collagen and / or amino acid polymer.

[0012] Optionally, the recombinant collagen includes one or more of type I, type II, type III, type V, type IV, and type XVII; the amino acid polymer includes oligopeptide and / or polypeptide.

[0013] Optionally, the dicarboxylic acid includes one or more of malic acid, tartaric acid, succinic acid, and maleic acid.

[0014] Optionally, the solvent includes water.

[0015] Preferably, the mass ratio of the polymer derivative to the dicarboxylic acid is 50-200:1.

[0016] Preferably, the total mass fraction of the polymer derivative and the dicarboxylic acid in the mixed solution is 1-5%.

[0017] Optionally, the cellulose-based polymer includes one or more of methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and sodium carboxymethyl cellulose.

[0018] Preferably, the ratio of the total mass of the polymer derivative and the dicarboxylic acid to the mass of the cellulose-based polymer is 1-5:5-50.

[0019] Preferably, the mass fraction of the cellulose-based polymer in the mixed solution after adding the cellulose-based polymer is 4-10%.

[0020] In the present invention, the mixing time is preferably 4-24 h, and more preferably 4-8 h.

[0021] In the present invention, the drying temperature is preferably 50-80 °C, the time is preferably 24-120 h, and more preferably 30-80 h. The present invention does not specifically limit the drying method, and common drying methods such as air drying, vacuum drying, freeze drying, spray drying, and fluidized bed drying can be used.

[0022] In the present invention, the particle size of the granular materials is preferably 0.05-5 mm, and more preferably 0.1-1 mm.

[0023] In the present invention, the temperature of the esterification cross-linking reaction is preferably 100-150°C, and the time is preferably 1-24 h, more preferably 3-10 h.

[0024] The present invention effectively solves the problems of poor swelling degree and strength of the edible hydrogel provided by the prior art that can provide energy for the body and achieves excellent technical effects:

[0025] In the recombinant collagen and amino acid polymers (oligopeptides and polypeptides) used in the present invention, the main chain ends and side chains contain rich carboxyl, amino and other active groups, which can react with polysaccharide chains as cross-linking agents. Among them, the recombinant collagen and amino acid polymers (oligopeptides and polypeptides) on the one hand belong to cross-linking agents, forming a relatively loose polymer network, which can improve the swelling effect. On the other hand, the addition of recombinant collagen and amino acid polymers (oligopeptides and polypeptides) can also be used as an energy substance to provide energy for the body and prevent the problem of malnutrition caused by long-term reduction of food intake.

[0026] In addition, the present invention uses a dicarboxylic acid (such as malic acid) as another cross-linking agent, which can form a smaller cross-linked pore structure. Combined with the larger cross-linked pore structure formed by the recombinant collagen and amino acid polymers (oligopeptides and polypeptides), a double-crosslinking method is formed to obtain a polymer hydrogel with a double-network structure, which helps to improve the swelling degree and strength of the obtained polymer hydrogel, and effectively solves the problems of poor swelling degree and strength of the edible hydrogel provided by the prior art that can provide energy for the body.

[0027] The second technical solution of the present invention: Provide the polymer hydrogel prepared by the above preparation method.

[0028] The third technical solution of the present invention: Provide the application of the polymer hydrogel in the preparation of weight loss products.

[0029] The present invention discloses the following technical effects:

[0030] 1. The present invention uses a high molecular derivative including recombinant collagen and amino acid polymers (oligopeptides and polypeptides) and a dicarboxylic acid as cross-linking agents, and a cellulose-based polymer as a substrate, and undergoes a chemical cross-linking reaction at a certain temperature to form a double-crosslinked network structure, obtaining an edible polymer hydrogel with high swelling degree and high strength.

[0031] 2. The polymer hydrogel obtained by the present invention can also provide energy for the body and prevent the problem of malnutrition caused by long-term reduction of food intake.

[0032] 3. The raw materials used in the present invention are simple and easy to obtain, and the preparation method is simple, which is more suitable for industrial application. Specific embodiments

[0033] A detailed description of various exemplary embodiments of the present invention is provided below. This detailed description should not be construed as a limitation on the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0034] It should be understood that the terms used in the present invention are merely for describing specific embodiments and are not intended to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0035] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0036] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the specification of the present invention are also obvious to those skilled in the art. The specification and examples of the present invention are merely exemplary.

[0037] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0038] The recombinant collagen used in the following examples and comparative examples of the present invention was purchased from Jiangsu Chuangjian Medical Technology Co., Ltd.

[0039] The polypeptides used in the following examples and comparative examples of the present invention were purchased from Shanghai Hongtai Biotech Co., Ltd.

[0040] Other raw materials used in the following examples, comparative examples, and performance tests of the present invention are all commercially available products unless otherwise specified.

[0041] Unless otherwise specified, the room temperature involved in the following examples, comparative examples, and performance tests of the present invention is calculated as 25 ± 5°C.

[0042] Example 1

[0043] Step 1: At room temperature, dissolve type III recombinant collagen and malic acid in purified water, where the mass ratio of type III recombinant collagen to malic acid is 80:1, to obtain mixed solution I. The total mass fraction of type III recombinant collagen and malic acid in mixed solution I is 2%;

[0044] Step 2: Add sodium carboxymethylcellulose to the mixed solution I obtained in Step 1, where the mass ratio of the total mass of type III recombinant collagen and malic acid to the mass of sodium carboxymethylcellulose is 2:5. After adding sodium carboxymethylcellulose, the mass fraction of sodium carboxymethylcellulose in mixed solution I is 5%. Stir and mix for 5 h to obtain mixed solution II;

[0045] Step 3: Pour the mixed solution II from Step 2 into a stainless-steel tray and dry it in a forced-air oven at 80 °C for 48 h to evaporate the water and obtain a dry material;

[0046] Step 4: Crush the dry material into particles with a particle size of 0.1 - 1 mm;

[0047] Step 5: Carry out an esterification cross-linking reaction on the crushed particles obtained in Step 4 at 120 °C for 3 h to obtain a polymer hydrogel.

[0048] Example 2

[0049] Step 1: At room temperature, dissolve type I recombinant collagen and malic acid in purified water, where the mass ratio of type I recombinant collagen to malic acid is 170:1, to obtain mixed solution I. The total mass fraction of type I recombinant collagen and malic acid in mixed solution I is 3%;

[0050] Step 2: Add hydroxypropyl cellulose to the mixed solution I obtained in Step 1, where the mass ratio of the total mass of type IV recombinant collagen and malic acid to the mass of hydroxypropyl cellulose is 3:10. After adding hydroxypropyl cellulose, the mass fraction of hydroxypropyl cellulose in mixed solution I is 7%. Stir and mix for 24 h to obtain mixed solution II;

[0051] Step 3: Pour the mixed solution II from Step 2 into a stainless-steel tray and dry it in a forced-air oven at 60 °C for 120 h to evaporate the water and obtain a dry material;

[0052] Step 4: Crush the dry material into particles with a particle size of 0.1 - 1 mm;

[0053] Step 5: Carry out an esterification cross-linking reaction on the crushed particles obtained in Step 4 at 100 °C for 24 h to obtain a polymer hydrogel.

[0054] Example 3

[0055] Step 1: At room temperature, dissolve the polypeptide and malic acid in purified water, where the mass ratio of the polypeptide to malic acid is 100:1, to obtain a mixed solution I. The total mass fraction of the polypeptide and malic acid in the mixed solution I is 5%;

[0056] Step 2: Add hydroxypropyl methylcellulose to the mixed solution I described in Step 1, where the mass ratio of the total mass of type III recombinant collagen and malic acid to the mass of hydroxypropyl methylcellulose is 3:17. After adding hydroxypropyl methylcellulose, the mass fraction of hydroxypropyl cellulose in the mixed solution I is 5%. Stir and mix for 12 h to obtain a mixed solution II;

[0057] Step 3: Pour the mixed solution II from Step 2 into a stainless-steel tray and dry it in a forced-air oven at 70 °C for 80 h to evaporate the water and obtain a dried material;

[0058] Step 4: Crush the dried material into particles with a particle size of 0.1 - 1 mm;

[0059] Step 5: Carry out an esterification cross-linking reaction on the crushed particles obtained in Step 4 at 120 °C for 10 h to obtain a polymer hydrogel.

[0060] Comparative Example 1

[0061] The difference from Example 1 is that the addition of type III recombinant collagen is omitted, and the others are the same as in Example 1. Specifically:

[0062] Step 1: At room temperature, dissolve malic acid in purified water to obtain a mixed solution I. The mass fraction of malic acid in the mixed solution I is 2%;

[0063] Step 2: Add sodium carboxymethylcellulose to the mixed solution I described in Step 1, where the mass ratio of malic acid to sodium carboxymethylcellulose is 2:5. After adding sodium carboxymethylcellulose, the mass fraction of sodium carboxymethylcellulose in the mixed solution I is 5%. Stir and mix for 5 h to obtain a mixed solution II;

[0064] Step 3: Pour the mixed solution II from Step 2 into a stainless-steel tray and dry it in a forced-air oven at 80 °C for 48 h to evaporate the water and obtain a dried material;

[0065] Step 4: Crush the dried material into particles with a particle size of 0.1 - 1 mm;

[0066] Step 5: Carry out an esterification cross-linking reaction on the crushed particles obtained in Step 4 at 120 °C for 3 h to obtain a polymer hydrogel.

[0067] Comparative Example 2

[0068] The difference from Example 1 is that the addition of malic acid is omitted, and the others are the same as in Example 1. Specifically:

[0069] Step 1: At room temperature, dissolve type III recombinant collagen in purified water to obtain mixed solution I, where the mass fraction of type III recombinant collagen in mixed solution I is 2%.

[0070] Step 2: Add sodium carboxymethylcellulose to the mixed solution I described in Step 1, where the mass ratio of type III recombinant collagen to sodium carboxymethylcellulose is 2:5. After adding sodium carboxymethylcellulose, the mass fraction of sodium carboxymethylcellulose in mixed solution I is 5%. Stir and mix for 5 h to obtain mixed solution II.

[0071] Step 3: Pour the mixed solution II from Step 2 into a stainless-steel tray and dry it in a forced-air oven at 80 °C for 48 h to evaporate the water and obtain a dried material.

[0072] Step 4: Crush the dried material into particles with a particle size of 0.1 - 1 mm.

[0073] Step 5: Carry out an esterification cross-linking reaction on the crushed particles obtained in Step 4 at 120 °C for 3 h to obtain a polymer hydrogel.

[0074] Performance testing:

[0075] Carry out performance testing on the polymer hydrogels obtained in Examples 1 - 3 and Comparative Examples 1 - 2.

[0076] 1. Swelling degree:

[0077] Testing method:

[0078] (1) Place a dry sintered glass funnel on a stand and pour 40.0 ± 1.0 g of purified water into the funnel.

[0079] (2) Wait until no droplets are detected in the funnel neck (about 5 min) and dry the tip of the funnel with absorbent paper.

[0080] (3) Place the funnel in a dry empty glass beaker (beaker 1), place it on a balanced scale, and record the weight of the empty beaker and the funnel (denoted as W 配平 ).

[0081] (4) Place a magnetic stir bar in a 100 mL beaker (beaker 2); place beaker 2 on the balance and balance it.

[0082] (5) Add a mixed solution of 40.0 ± 1.0 g of simulated gastric fluid (SGF) and water (volume ratio 1:8) to beaker 2.

[0083] (6) Place beaker 2 on a magnetic stirrer and stir at room temperature.

[0084] (7) Accurately weigh 0.250 ± 0.005 g of the polymer hydrogel powder using weighing paper, and record the mass of the weighed polymer hydrogel powder (denoted as W in ).

[0085] (8) Add the powder to beaker 2 and stir with a magnetic stirrer for 30 ± 2 min without generating vortices.

[0086] (9) Remove the stir bar from the resulting suspension, place the funnel on a stand, pour the suspension into the funnel, and collect the remaining material with a spatula.

[0087] (10) Allow the material to drain for 20 ± 2 min.

[0088] (11) Place the funnel containing the drained material in beaker 1 and weigh it (denoted as W’ fin ).

[0089] Calculate the swelling degree according to the following formula:

[0090] Swelling degree = (W fin - W in ) / W in ;

[0091] In the formula, W fin is the weight of the swollen polymer hydrogel calculated according to the formula W fin = W’ fin - W 配平 ; W in is the weight of the initial dry sample.

[0092] The results are shown in Table 1.

[0093] Table 1 Swelling degrees of the polymer hydrogels obtained in Examples 1 - 3 and Comparative Examples 1 - 2

[0094] Sample Swelling degree Example 1 78.56 Example 2 77.04 Example 3 65.38 Comparative Example 1 41.25 Comparative Example 2 47.19

[0095] 2. Storage modulus:

[0096] Detection method: Test the rheological mechanical properties of the hydrogel according to the swelling degree test method. Place the obtained hydrogels between the parallel plates (40 mm) of a rotational rheometer respectively. Test parameters: 0.1 - 100 rad / s, temperature 37°C, working height 1 mm. Obtain the modulus diagram of 0.1 - 100 rad / s, and select the storage modulus at 15.8 rad / s as the storage modulus of the product. The results are shown in Table 2.

[0097] Table 2 Storage moduli of the polymer hydrogels obtained in Examples 1 - 3 and Comparative Examples 1 - 2

[0098] Sample Storage modulus (Pa) Example 1 315 Example 2 284 Example 3 231 Comparative Example 1 135 Comparative Example 2 152

[0099] As can be seen from Tables 1 to 2, the present invention uses a high molecular derivative including recombinant collagen and amino acid polymers (oligopeptides and polypeptides) and a dicarboxylic acid as a crosslinking agent, and a cellulose-based polymer as a substrate, and undergoes a chemical crosslinking reaction at a certain temperature to form a double crosslinked network structure, obtaining an edible polymer hydrogel with a high swelling degree and high strength. At the same time, the obtained polymer hydrogel can also provide energy for the body and prevent the problem of malnutrition caused by long-term reduction of food intake.

[0100] The various embodiments in this specification are described in a progressive manner. Each embodiment focuses on the differences from other embodiments. For the same or similar parts among the various embodiments, reference can be made to each other.

[0101] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a polymer hydrogel for weight management, characterized in that: The steps include: dissolving the polymer derivative and the dicarboxylic acid in a solvent to obtain a mixed solution; Adding cellulose polymer to the mixed solution, mixing and drying to obtain a granular material; Performing an esterification and cross-linking reaction on the granular material to obtain the polymer hydrogel; The polymer derivatives include recombinant collagen and / or amino acid polymers.

2. The preparation method according to claim 1, characterized in that: The recombinant collagen includes one or more of type I, type II, type III, type V, type IV and type XVII; the amino acid polymer includes oligopeptides and / or polypeptides.

3. The preparation method according to claim 1, characterized in that: The dicarboxylic acid comprises one or more of malic acid, tartaric acid, succinic acid and maleic acid; and / or the solvent comprises water; and / or the mass ratio of the polymer derivative to the dicarboxylic acid is 50 to 200:1; and / or the total mass fraction of the polymer derivative and the dicarboxylic acid in the mixed solution is 1 to 5%.

4. The preparation method according to claim 1, characterized in that: The cellulose polymer includes one or more of methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and sodium carboxymethyl cellulose; and / or, the ratio of the total mass of the polymer derivative and the dicarboxylic acid to the mass of the cellulose polymer is 1-5:5-50; and / or, after the cellulose polymer is added, the mass fraction of the cellulose polymer in the mixed solution is 4-10%.

5. The preparation method according to claim 1, characterized in that: The mixing time is 4 to 24 hours.

6. The preparation method according to claim 1, characterized in that: The drying temperature is 50-80° C. and the drying time is 24-120 hours.

7. The preparation method according to claim 1, characterized in that: The particle size of the granular material is 0.05-5 mm.

8. The preparation method according to claim 1, characterized in that: The temperature of the esterification cross-linking reaction is 100-150° C., and the time is 1-24 hours.

9. The polymer hydrogel prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the polymer hydrogel according to claim 9 in preparing weight loss products.