A high-absorbability hydrogel and a preparation method and application thereof

Abstract

The application provides a high-absorbing hydrogel and a preparation method and application thereof, and belongs to the technical field of hydrogel preparation.The high-absorbing hydrogel is prepared by cross-linking reaction of recombinant collagen or a peptide compound as a cross-linking agent and sodium carboxymethyl cellulose, the cross-linking agent contains rich carboxyl and amino groups at both ends and side chains of the main chain, can react with polysaccharide chains in the sodium carboxymethyl cellulose, and generates a loose polymer network, so that the water absorption ratio is improved; on the other hand, the addition of the recombinant collagen or the peptide compound can also serve as an energy material to provide energy for the body and prevent malnutrition caused by long-term reduction of food intake.

Description

Technical Field

[0001] The present invention belongs to the technical field of hydrogel preparation, and in particular relates to a highly absorbent hydrogel and a preparation method and application thereof. Background Art

[0002] A hydrogel is a hydrophilic, three-dimensional network-like gel that absorbs water, causing it to swell to multiples of its initial volume. Hydrogels are typically composed of natural or synthetic polymers cross-linked physically (non-covalently) or chemically (covalently) (Reference 1: JIANG Q, ZHOU W, WANG J, et al. Hypromellose succinate-crosslinked chitosan hydrogel films for potential wound dressing [J]. International Journal of Biological Macromolecules, 2016, 91: 85-91.). Highly absorbent hydrogels can absorb 10 times their own weight, and some can even absorb more than 1,000 times their own weight, demonstrating exceptional absorption properties.

[0003] Specifically, hydrogels, as a type of macromolecular polymer, can be produced by physical or chemical crosslinking. Physical crosslinking is usually formed by intermolecular association through hydrogen bonds, interionic forces, crystallization, hydrophobic interactions, etc. This intermolecular interaction force is generally reversible, so it will make the hydrogel less stable and have poor mechanical strength. Chemical crosslinking, on the other hand, is formed by covalent bonds between polymer chains. Compared with intermolecular forces, chemical bonds are stronger, thus giving the hydrogel more stable and stronger properties. The chain length of the crosslinking agent used in the chemical crosslinking method will affect the water absorption rate and mechanical strength. When using a short crosslinking agent such as a dicarboxylic acid, due to its short length, after crosslinking with a polysaccharide chain at one end, the other end can only react with the same polysaccharide chain or another adjacent polysaccharide chain, which will lead to the formation of intramolecular crosslinking or a tightly connected intermolecular crosslinked network structure. This dense structure is not conducive to the retention of water molecules and reduces the swelling degree of the product. Therefore, in the preparation technology of hydrogels, chemical crosslinking can produce a stable and rigid polymer network structure compared to physical crosslinking. The chain length of the crosslinker affects the water absorption capacity and strength of the hydrogel. Existing technologies generally use crosslinkers with short chain lengths to produce a denser molecular structure, but this also leads to problems such as low mechanical strength and low water absorption of the hydrogel.

[0004] Highly absorbable hydrogels are commonly used in the medical field as gastrointestinal fillers. Upon ingestion, they absorb body fluids and expand, taking up space in the gastrointestinal tract and promoting a feeling of fullness. However, most hydrogels currently used as gastric fillers on the market are cellulose-based polysaccharides, which are not absorbed by the human body. Furthermore, their expansion in the gastrointestinal tract can reduce food intake, and long-term use can lead to malnutrition.

[0005] Therefore, it is necessary to develop a new hydrogel product that can not only give a sense of fullness but also provide energy to the body. Summary of the Invention

[0006] To solve the above technical problems, the present invention proposes a highly absorbent hydrogel, its preparation method and application. Recombinant collagen / peptide compounds and sodium carboxymethyl cellulose are used as raw materials, and a chemical cross-linking reaction occurs at a certain temperature to form a loose polymer network structure. The resulting hydrogel has a high swelling rate, which can provide a sense of fullness while also providing energy to the human body.

[0007] To achieve the above objectives, the present invention provides the following technical solutions:

[0008] One of the technical solutions of the present invention:

[0009] A method for preparing a highly absorbent hydrogel is provided, wherein recombinant collagen or a peptide compound is used as a crosslinking agent and crosslinked with sodium carboxymethyl cellulose to prepare the hydrogel, comprising the following steps:

[0010] dissolving the cross-linking agent in water to obtain solution I;

[0011] adding sodium carboxymethyl cellulose to the solution I to obtain a solution II;

[0012] The solution II is dried and crushed into particles, which are then heated to undergo esterification and cross-linking reaction to obtain the highly absorbent hydrogel.

[0013] Recombinant collagen is the earliest discovered and most abundant type of extracellular matrix protein, and is widely present in the skin, muscles, bones and internal organs of humans and animals. Collagen is widely used in food, cosmetics, nutritional supplements and other fields because of its excellent physical and chemical properties, biological efficacy, biocompatibility, and biodegradability. According to the source, collagen is roughly divided into animal collagen and recombinant collagen. Due to the potential pathogenic risks and immunogenicity of animal collagen, with the development of synthetic biology, the market share of recombinant collagen continues to increase. At the same time, the hydrolysis products of proteins, oligopeptides (the number of amino acids on the peptide chain is less than 10) or polypeptides (the number of amino acids on the peptide chain is between 10 and 50) can also be used as long-chain cross-linking agents to prepare highly absorbent hydrogels.

[0014] The present invention uses recombinant collagen or peptide compounds with long chains as cross-linking agents. Because the chain length of such cross-linking agents is longer, when the cross-linking agent is cross-linked with the polysaccharide chains in sodium carboxymethyl cellulose, the other end has a larger range of movement and is more likely to cross-link with more polysaccharide chains, increasing the cross-linking between molecules. At the same time, the cross-linking network structure is looser, and the pores are enlarged to accommodate more water molecules, thereby improving the water absorption rate.

[0015] Furthermore, the mass concentration of the cross-linking agent in the solution I is 1-6%.

[0016] Furthermore, the mass concentration of sodium carboxymethyl cellulose in the solution II is 6-10%.

[0017] Furthermore, the recombinant collagen is selected from one or more of type I, type II, type III, type V, type IV and type XVII.

[0018] Furthermore, the peptide compound is selected from one or more oligopeptides or polypeptides.

[0019] Furthermore, the drying temperature is 40-60° C., and the drying time is 24-120 h, preferably 48-72 h.

[0020] Furthermore, the temperature of the esterification cross-linking reaction is 100-150° C., and the time is 1-24 hours, preferably 3-8 hours.

[0021] Furthermore, the particle size of the particles is 0.05-5 mm, preferably 0.1-1 mm.

[0022] The second technical solution of the present invention:

[0023] A highly absorbent hydrogel is prepared according to the above preparation method.

[0024] The third technical solution of the present invention:

[0025] The highly absorbent hydrogel is used in the preparation of medicines for treating overweight or obesity.

[0026] The fourth technical solution of the present invention:

[0027] Application of the highly absorbent hydrogel in preparing medicine for treating sleep apnea.

[0028] The fifth technical solution of the present invention:

[0029] The highly absorbent hydrogel is used in the preparation of medicines for treating diabetes.

[0030] Compared with the prior art, the present invention has the following advantages and technical effects:

[0031] (1) The present invention uses recombinant collagen or peptide compounds as cross-linking agents. The main chain ends and side chains of the cross-linking agents contain rich carboxyl and amino groups, which can react with the polysaccharide chains in sodium carboxymethyl cellulose to form a loose polymer network, thereby improving the water absorption rate. On the other hand, the addition of recombinant collagen or peptide compounds can also serve as an energy substance to provide energy for the body and prevent malnutrition caused by long-term reduction in food intake.

[0032] (2) The present invention proposes for the first time to prepare a hydrogel by cross-linking recombinant collagen / peptide compounds into sodium carboxymethyl cellulose. The preparation method is simple, safe and non-toxic. After consuming the hydrogel of the present invention, the user can feel full and provide energy to the body, thereby broadening the selection of gastrointestinal fillers. DETAILED DESCRIPTION

[0033] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting 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 described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any intermediate value within a stated value or stated range and any other stated value or intermediate value within the stated range is also encompassed by the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0035] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice 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 associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0036] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be illustrative only.

[0037] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0038] The embodiment of the present application provides a preparation method of a high-absorbability hydrogel, which is prepared by cross-linking reaction of recombinant collagen or a peptide compound as a cross-linking agent and sodium carboxymethyl cellulose, and specifically comprises the following steps:

[0039] The cross-linking agent is dissolved in water to obtain solution I;

[0040] The sodium carboxymethyl cellulose is added to the solution I to obtain solution II;

[0041] The solution II is dried and crushed into particles, and then esterification cross-linking reaction is carried out by heating to obtain the high-absorbability hydrogel.

[0042] In the preferred embodiment of the present application, the mass concentration of the cross-linking agent in the solution I is 1-6%, and preferably the mass concentration is 5%.

[0043] In the preferred embodiment of the present application, the mass concentration of the sodium carboxymethyl cellulose in the solution II is 6-10%, and preferably the mass concentration is 6%.

[0044] In the preferred embodiment of the present application, the recombinant collagen is selected from one or more of type I, type II, type III, type V, type IV and type XI type.

[0045] Recombinant collagen is divided into different types according to its molecular structure, tissue distribution, physiological function and gene coding, including type I, type II, type III, type V, type IV and type XI type. The following are the main differences between these types:

[0046] Type I collagen: This is the most common type of collagen, mainly present in skin, bone, tendon and other connective tissues, providing structural support and strength to tissues.

[0047] Type II collagen: mainly present in cartilage tissue, is a key component to maintain joint health and elasticity.

[0048] Type III collagen: present in skin, blood vessels, muscles and internal organs, helps maintain the elasticity and stability of these tissues.

[0049] Type IV collagen: mainly present in basement membranes, plays an important role in supporting and separating tissue cells.

[0050] Type V collagen: usually exists together with type I and type II collagens, affects the assembly of extracellular matrix and cell adhesion.

[0051] Type XI type collagen: mainly coexists with type I and type II collagens, participates in the regulation of collagen fiber diameter and the integrity of tissue structure.

[0052] In the preferred embodiment of the present application, the peptide compound is selected from one or more of oligopeptides or polypeptides.

[0053] During the hydrolysis process, the triple helix structure of the protein is destroyed, and it is decomposed into polypeptides or oligopeptides with relatively small molecular weight. Oligopeptides generally refer to peptides composed of 2 to 10 amino acid residues, with small molecular weight, usually less than 1000 Dalton. Polypeptides refer to peptides composed of more than 10 but less than 50 amino acid residues, with molecular weight between 1000 and 10000 Dalton.

[0054] In the preferred embodiment of the present application, the drying temperature is 40-60℃, and the time is 24-120h, preferably 48-72h.

[0055] In the preferred embodiment of the present application, the esterification cross-linking reaction temperature is 100-150℃, and the time is 1-24h, preferably 3-8h.

[0056] In the preferred embodiment of the present application, the particle size of the particles is 0.05-5mm, preferably 0.1-1mm.

[0057] The embodiment of the present application also provides a high-absorbency hydrogel prepared according to the preparation method.

[0058] In the embodiment of the present application, room temperature refers to "20-25℃".

[0059] In the embodiment of the present application, the recombinant collagen used is type III recombinant collagen, purchased from Jiangsu Chuangjian Medical Technology Co., Ltd. The carboxymethyl cellulose sodium used is purchased from Anhui Shanhe Pharmaceutical Auxiliary Co., Ltd. The oligopeptides and polypeptides used are purchased from Shanghai Hongpeptide Biotechnology Co., Ltd., wherein the polypeptide sequence is DDDDKAPFFDDDD, and the oligopeptide sequence is DDDDKAPFF.

[0060] The technical solutions of the present application are further described below through examples.

[0061] Example 1

[0062] (1) Dissolve the type III recombinant collagen in water at room temperature to obtain a solution I with a mass concentration of 5%;

[0063] (2) Add carboxymethyl cellulose sodium to the solution I obtained in step (1) and stir for 5h to obtain solution II, wherein the mass concentration of carboxymethyl cellulose sodium in solution II is 6%;

[0064] (3) Pour the solution II of step (2) into a stainless steel tray, dry in a 50℃ air oven for 72h, and evaporate the water to obtain a dry material;

[0065] (4) crushing the dried material into particles with a particle size of 0.1-1 mm;

[0066] (5) The particles obtained in step (4) were heated at 120° C. for esterification and cross-linking reaction for 5 h to obtain a highly absorbent hydrogel.

[0067] Example 2

[0068] (1) Dissolving type I recombinant collagen in water at room temperature to obtain solution I with a mass concentration of 6%;

[0069] (2) adding sodium carboxymethyl cellulose to solution I obtained in step (1) and stirring for 5 hours to obtain solution II, wherein the mass concentration of sodium carboxymethyl cellulose in solution II is 10%;

[0070] (3) Pour solution II from step (2) into a stainless steel dish and dry it in a forced air oven at 60°C for 24 hours to evaporate the water to obtain a dry material;

[0071] (4) crushing the dried material into particles with a particle size of 0.05-1 mm;

[0072] (5) The particles obtained in step (4) were heated at 150° C. for esterification and cross-linking reaction for 1 h to obtain a highly absorbent hydrogel.

[0073] Example 3

[0074] (1) Dissolve type III recombinant collagen in water at room temperature to obtain solution I with a mass concentration of 1%;

[0075] (2) adding sodium carboxymethyl cellulose to solution I obtained in step (1) and stirring for 5 hours to obtain solution II, wherein the mass concentration of sodium carboxymethyl cellulose in solution II is 6%;

[0076] (3) Pour solution II from step (2) into a stainless steel dish and dry it in a blast oven at 40°C for 120 h to evaporate the water to obtain a dry material;

[0077] (4) crushing the dried material into particles with a particle size of 0.2-1.2 mm;

[0078] (5) The particles obtained in step (4) were heated at 100° C. for esterification and cross-linking reaction for 24 h to obtain a highly absorbent hydrogel.

[0079] Example 4

[0080] (1) Dissolve type III recombinant collagen in water at room temperature to obtain solution I with a mass concentration of 3%;

[0081] (2) adding sodium carboxymethyl cellulose to solution I obtained in step (1) and stirring for 5 hours to obtain solution II, wherein the mass concentration of sodium carboxymethyl cellulose in solution II is 8%;

[0082] (3) Pour solution II from step (2) into a stainless steel plate and dry it in a blast oven at 50°C for 48 hours to evaporate the water to obtain a dry material;

[0083] (4) crushing the dried material into particles with a particle size of 0.1-1 mm;

[0084] (5) The particles obtained in step (4) were heated at 130° C. for esterification and cross-linking reaction for 8 h to obtain a highly absorbent hydrogel.

[0085] Example 5

[0086] (1) Dissolve the polypeptide in water at room temperature to obtain a solution I with a mass concentration of 5%;

[0087] (2) adding sodium carboxymethyl cellulose to solution I obtained in step (1) and stirring for 5 hours to obtain solution II, wherein the mass concentration of sodium carboxymethyl cellulose in solution II is 6%;

[0088] (3) Pour solution II from step (2) into a stainless steel dish and dry it in a blast oven at 50°C for 72 hours to evaporate the water to obtain a dry material;

[0089] (4) crushing the dried material into particles with a particle size of 0.1-1 mm;

[0090] (5) The particles obtained in step (4) were heated at 120° C. for esterification and cross-linking reaction for 5 h to obtain a highly absorbent hydrogel.

[0091] Example 6

[0092] (1) Dissolve the oligopeptide in water at room temperature to obtain solution I with a mass concentration of 5%;

[0093] (2) adding sodium carboxymethyl cellulose to solution I obtained in step (1) and stirring for 5 hours to obtain solution II, wherein the mass concentration of sodium carboxymethyl cellulose in solution II is 6%;

[0094] (3) Pour solution II from step (2) into a stainless steel dish and dry it in a blast oven at 50°C for 72 hours to evaporate the water to obtain a dry material;

[0095] (4) crushing the dried material into particles with a particle size of 0.1-1 mm;

[0096] (5) The particles obtained in step (4) were heated at 120° C. for esterification and cross-linking reaction for 5 h to obtain a highly absorbent hydrogel.

[0097] Comparative Example 1

[0098] (1) At room temperature, tartaric acid was dissolved in water to obtain a solution I with a mass concentration of 0.02%;

[0099] (2) adding sodium carboxymethyl cellulose to solution I obtained in step (1) and stirring for 5 hours to obtain solution II, wherein the mass concentration of sodium carboxymethyl cellulose in solution II is 6%;

[0100] (3) Pour solution II from step (2) into a stainless steel dish and dry it in a blast oven at 50°C for 72 hours to evaporate the water to obtain a dry material;

[0101] (4) crushing the dried material into particles with a particle size of 0.1-1 mm;

[0102] (5) The particles obtained in step (4) were heated at 120° C. for esterification and cross-linking reaction for 5 h to obtain a hydrogel.

[0103] Comparative Example 2

[0104] Steps (2) to (5) are the same as those in Example 1, except that in step (1), type III recombinant collagen is dissolved in water at room temperature to obtain solution I with a mass concentration of 10%.

[0105] Comparative Example 3

[0106] Steps (1) to (4) are the same as those in Example 1, except that in step (5), the particles obtained in step (4) are heated at 160° C. to perform an esterification cross-linking reaction, and the reaction time is 36 h.

[0107] Comparative Example 4

[0108] Steps (1) and (3)-(5) are the same as those in Example 1, except that step (2) is to add sodium carboxymethyl cellulose to solution I obtained in step (1) and stir and mix for 5 hours to obtain solution II, wherein the mass concentration of sodium carboxymethyl cellulose in solution II is 3%.

[0109] Swelling test

[0110] (1) Place a dry sintered glass funnel on a stand and pour 40.0 ± 1.0 g of pure water into the funnel;

[0111] (2) Wait until no droplets are detected in the funnel neck (about 5 minutes) and dry the funnel tip with absorbent paper;

[0112] (3) Place the funnel into a dry empty glass beaker (Beaker 1), place it on a balanced balance and record the weight of the empty device (W 配平 );

[0113] (4) Place a magnetic stirring bar in a 100 mL beaker (Beaker 2), place Beaker 2 on a balance, and balance it.

[0114] (5) Add 40.0 ± 1.0 g of SGF / water (mass ratio 1:8) solution to beaker 2;

[0115] (6) Place beaker 2 on a magnetic stirrer and stir slowly at room temperature;

[0116] (7) Use weighing paper to accurately weigh 0.250±0.005g of the hydrogel powder of Examples 1-6 and Comparative Examples 1-4 (W in );

[0117] (8) Add the above powder to beaker 2 and stir slowly with a magnetic stirrer without creating a vortex for 30 ± 2 minutes;

[0118] (9) Remove the stirring rod from the resulting suspension, place the funnel on a stand and pour the suspension into the funnel, using a spatula to collect any remaining material;

[0119] (10) Excretion of substances, lasting 20 ± 2 minutes;

[0120] (11) Place the funnel containing the discharged material in beaker 1 and weigh it (W ’ fin ).

[0121] The swelling degree was calculated according to the following formula:

[0122] Swelling degree = (W fin -W in ) / W in .

[0123] W fin is the weight of the swollen hydrogel calculated as follows: fin =W ’ fin –W 配平 ;

[0124] W in is the weight of the initial dry sample.

[0125] The swelling test results of Examples 1-6 and Comparative Examples 1-4 are shown in Table 1.

[0126] Table 1 Swelling test results of Examples 1-6 and Comparative Examples 1-4

[0127] sample Swelling degree Example 1 95.35 Example 2 97.48 Example 3 90.26 Example 4 94.54 Example 5 88.51 Example 6 87.25 Comparative Example 1 64.43 Comparative Example 2 52.14 Comparative Example 3 47.23 Comparative Example 4 55.16

[0128] As can be seen from Table 1, when recombinant collagen is added as a cross-linking agent (Example 1), the swelling degree is greatly improved compared with tartaric acid (Comparative Example 1). This is because recombinant collagen provides a longer chain length as a cross-linking agent. In the cross-linked structure, a loose polymer network structure can be formed, which helps to increase the water absorption rate of the hydrogel.

[0129] Compared with Example 1, Comparative Example 2 changes the concentration of type III recombinant collagen in water to 10%. Excessively high crosslinking agent content will increase the crosslinking density, resulting in smaller gaps between polymer networks and difficulty for water molecules to penetrate into the polymer, thereby reducing the swelling degree.

[0130] Compared with Example 1, Comparative Example 3 changed the temperature and time of the esterification cross-linking reaction. Although the cross-linking agent content was appropriate, excessive cross-linking temperature would lead to excessive cross-linking, affecting the penetration of water molecules and thus reducing the swelling degree.

[0131] Compared with Example 1, Comparative Example 4 changes the mass concentration of sodium carboxymethyl cellulose in Solution II, which leads to a decrease in solid content concentration. In contrast, the content of the crosslinking agent is too high, which similarly leads to an increase in the crosslinking density, thereby reducing the swelling degree.

[0132] The present invention uses recombinant collagen and its hydrolyzed oligopeptides or polypeptides as crosslinking agents. The crosslinking agents contain abundant carboxyl and amino groups at both ends of the main chain and in the side chains. These crosslinking agents can react with the polysaccharide chains in sodium carboxymethylcellulose to form a loose polymer network, thereby increasing water absorption. Furthermore, the addition of recombinant collagen or polypeptides can also serve as an energy source, providing energy to the body and preventing malnutrition caused by long-term reduced food intake. The present invention proposes for the first time that recombinant collagen / polypeptide crosslinking with sodium carboxymethylcellulose be used to produce a hydrogel. The preparation method is simple, safe, and non-toxic. Consuming the hydrogel of the present invention provides a sense of fullness and provides energy to the body, broadening the options for gastrointestinal fillers. For example, the highly absorbent hydrogel of the present invention can be used to prepare drugs for treating overweight or obesity, sleep apnea, or diabetes.

[0133] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A method for preparing a highly absorbent hydrogel, characterized in that: The preparation method is prepared by cross-linking recombinant collagen or peptide compounds with sodium carboxymethyl cellulose, comprising the following steps: dissolving the cross-linking agent in water to obtain solution I; adding sodium carboxymethyl cellulose to the solution I to obtain a solution II; The solution II is dried and crushed into particles, and then heated to perform an esterification and cross-linking reaction to obtain the highly absorbent hydrogel; The mass concentration of the cross-linking agent in the solution I is 1-6%; The mass concentration of sodium carboxymethyl cellulose in the solution II is 6%-10%; The peptide compound is a polypeptide, and the number of amino acids on the peptide chain of the polypeptide is 10-50; The temperature of the esterification cross-linking reaction is 100-150° C., and the time is 1-24 hours.

2. The method for preparing a highly absorbent hydrogel according to claim 1, wherein: The recombinant collagen is selected from one or more of type I, type II, type III, type V, type IV and type XVII.

3. The method for preparing a highly absorbent hydrogel according to claim 1, wherein: The drying temperature is 40-60° C. and the drying time is 24-120 hours.

4. The method for preparing a highly absorbent hydrogel according to claim 1, wherein: The particle size of the particles is 0.05-5 mm.

5. A highly absorbent hydrogel, characterized in that: Prepared according to the preparation method according to any one of claims 1 to 4.