Oral superabsorbent hydrogel capable of occupying volume in stomach and preparation method and application of oral superabsorbent hydrogel
By forming a hydrogel with a crosslinking network structure, the problem of insufficient mechanical strength and stability of sodium alginate hydrogel in drug carrier application is solved, the stability and controlled release of drugs in the digestive tract are achieved, and satiety is increased. and bioavailability of drugs.
Patent Information
- Application Number
- CN202411527818.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-30
- Publication Date
- 2025-02-18
AI Technical Summary
When used as a drug carrier, the existing sodium alginate hydrogel has low mechanical strength and poor stability. It is prone to breaking the mesh structure due to strong water absorption, which leads to sudden release of the drug, limiting its effect in drug carrier applications.
By ion-exchanging polymer materials that can undergo ion exchange with multivalent metal cations, a hydrogel with a cross-linking network structure is formed, and drug molecules are installed to improve the stability of the drug in the digestive tract and absorb water and expand during the digestion process. , occupy the space in the stomach and increase the feeling of fullness.
The drug protection and controlled release in the digestive tract are achieved, which increases satiety, improves the bioavailability of the drug and the targeted release effect of the intestinal tract.
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Figure CN119454575A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of biomedical materials and food science and technology, and in particular to an oral gastric volume-occupying superabsorbent hydrogel and a preparation method and application thereof. Background Art
[0002] According to the 2023 World Obesity Atlas report, 38% of the world’s population is currently overweight or obese, with a body mass index above 25kg / m 2 , it is estimated that by 2035, the global prevalence of overweight and obesity will reach 51%. Overweight and obesity not only affect body image, but also have the risk of causing chronic diseases such as cardiovascular and cerebrovascular diseases, hyperlipidemia, hypertension, diabetes, etc. It is well known that the root cause of obesity is excessive energy intake or insufficient energy consumption, which leads to energy imbalance in the body. Therefore, controlling energy intake and increasing energy consumption have become the main methods of weight management. The current various weight loss methods such as dieting, drugs and surgery have side effects such as malnutrition, damage to the liver and kidneys, and weight loss rebound. Increasing energy consumption through exercise requires a certain amount of time and energy. Therefore, people hope to have a health-friendly and convenient measure to replace the above-mentioned weight loss methods.
[0003] With the rise of related research, a dietary regulation strategy that uses increased satiety to limit energy intake has gradually been accepted by the public. Under isocaloric conditions, the more satiating the food is, the less people will want to eat. Studies have found that oral superabsorbent hydrogels (OSH) can absorb water and swell to physically occupy the effective space in the stomach under the human digestive environment, mimicking fiber-rich vegetables, making people feel full without increasing calories, thereby suppressing appetite and reducing energy intake; in addition, its composition and structure can also have significant benefits for intestinal and metabolic health.
[0004] Sodium alginate has good biocompatibility, biodegradability and low toxicity as a hydrogel material due to its wide availability, low price and high safety. At the same time, because it contains a large number of carboxyl and hydroxyl groups in the molecule and has high chemical activity, it can quickly form a hydrogel with a three-dimensional network structure under a relatively mild environment, and has been widely used in drug delivery systems. However, the mechanical strength of a single sodium alginate hydrogel is low and its stability is poor. When used as a drug carrier, its network structure is easily broken due to its strong water absorption, resulting in sudden release of drugs, which limits the application of sodium alginate hydrogel as a drug carrier.
[0005] Therefore, it is necessary to develop a new solution to optimize the performance of sodium alginate hydrogel and prepare oral gastric volume-occupying superabsorbent hydrogel. Summary of the invention
[0006] The present invention aims to provide an oral gastric volume-occupying super absorbent hydrogel, wherein the hydrogel is formed by exchanging ions between a polymer material capable of ion exchange and a multivalent metal cation to form a hydrogel with a cross-linked network structure, and the hydrogel carries drug molecules; the hydrogel can provide protection, improve the stability of drug molecules in the digestive fluid and digestive enzyme environment of the human digestive tract, and can absorb water to swell and occupy the space in the stomach, thereby achieving functions such as increasing satiety, improving drug bioavailability and intestinal targeted release.
[0007] In a first aspect, the present invention provides an oral gastric volume-occupying superabsorbent hydrogel, wherein the hydrogel comprises a polymer material capable of ion exchange, a natural polymer material, a material containing multivalent metal cations, and a loaded drug.
[0008] The hydrogel provided by the present invention will not be digested and degraded when in a mixed environment of digestive juice and digestive enzymes in the digestive tract, and has the function of protecting and controlling the release of loaded drugs. At the same time, it can absorb water and swell during digestion, fill the space in the stomach, and achieve the effect of increasing satiety.
[0009] Optionally, the polymer material capable of ion exchange includes sodium alginate.
[0010] Optionally, the natural polymer material includes at least one of inulin, collagen, chitosan, xanthan gum and gelatin.
[0011] Optionally, the metal cations in the material containing multivalent metal cations include Zn 2+ , Fe 3+ , Ba 2+ Cr 3+ and Ca 2+ At least one of them.
[0012] Optionally, the loaded drug includes white bean polysaccharide.
[0013] In a second aspect, the present invention provides a method for preparing an oral gastric volume-occupying superabsorbent hydrogel, comprising the following steps:
[0014] S1, dissolving the loaded drug in water to obtain solution A, dissolving the polymer material capable of ion exchange and the natural polymer material in solution A to obtain solution B and solution C, respectively, stirring and mixing solution B and solution C, and ultrasonically treating solution B and solution C to obtain a mixed solution;
[0015] S2, dissolving a material containing multivalent metal cations in water to obtain a solution D;
[0016] S3. Inject the mixed solution dropwise into solution D, let stand, filter, and wash with water to obtain an oral gastric volume-occupying super absorbent hydrogel.
[0017] The hydrogel preparation method provided by the invention is simple and convenient to operate.
[0018] Optionally, the concentration of the drug loaded in solution A in step S1 is (2-10) mg / mL.
[0019] Optionally, the concentration of the polymer material capable of ion exchange in the solution B in step S1 is (20-40) mg / mL.
[0020] Optionally, the concentration of the natural polymer material in the solution C in step S1 is (50-400) mg / mL.
[0021] Optionally, in step S1, the volume ratio of the solution B and the solution C is 1:(0.5-1.5).
[0022] Optionally, after the solution B and the solution C are mixed in step S1, ultrasound is required to remove excess bubbles.
[0023] Optionally, the concentration of the material containing multivalent metal cations in the solution D in step S2 is (0.1-0.2) mol / L.
[0024] Optionally, the inner diameter of the nozzle of the syringe used for the injection in step S3 is (1-2) mm.
[0025] Optionally, the standing time in step S3 is (30-40) min.
[0026] In a third aspect, the present invention provides an application of the above-mentioned oral gastric volume-occupying super absorbent hydrogel in drug loading and targeted delivery and functional health food processing.
[0027] When the hydrogel provided by the present invention is used in the processing of satiety food, it can produce a sense of satiety without increasing calories, thereby suppressing appetite, reducing energy intake, and being harmless to human health. BRIEF DESCRIPTION OF THE DRAWINGS
[0028] In order to more clearly introduce the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments.
[0029] Figure 1 This is a finished picture of the hydrogel prepared in the performance test;
[0030] Figure 2 FT-IR spectra of hydrogels with different ratios in performance testing;
[0031] Figure 3 It is the SEM image of hydrogels with different proportions in performance testing;
[0032] Figure 4It is a statistical diagram of the water content of hydrogels with different proportions in performance testing;
[0033] Figure 5 It is a statistical diagram of the swelling performance of hydrogels with different proportions in the performance test;
[0034] Figure 6 It is a statistical diagram of the encapsulation efficiency of hydrogels with different proportions in the performance test;
[0035] Figure 7 This is a test diagram of the digestion behavior of hydrogels with different ratios in performance testing;
[0036] Figure 8 It is a statistical diagram of the digestion swelling rate of hydrogels with different proportions in the performance test;
[0037] Fig. 9 This is a real-time recording diagram during hydrogel digestion in performance testing;
[0038] Fig.10 This is a test diagram of the drug release behavior of hydrogels with different ratios in performance testing. DETAILED DESCRIPTION
[0039] In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention will be further described through the following embodiments in conjunction with the accompanying drawings. However, the following embodiments are illustrative and are only used to specifically describe the present invention rather than to limit the present invention.
[0040] The invention provides an oral gastric volume-occupying super-absorbent hydrogel, which comprises a polymer material capable of ion exchange, a natural polymer material, a material containing multivalent metal cations and loaded drugs.
[0041] In some embodiments, the polymer material capable of ion exchange comprises sodium alginate.
[0042] In some embodiments, the natural polymer material includes at least one of inulin, collagen, chitosan, xanthan gum and gelatin.
[0043] In some embodiments, the metal cations in the material containing multivalent metal cations include Zn 2+ , Fe 3 + , Ba 2+ Cr 3+ and Ca 2+ At least one of them.
[0044] In some embodiments, the loaded drug comprises white bean polysaccharide.
[0045] The present invention also provides a method for preparing an oral gastric volume-occupying super absorbent hydrogel, comprising the following steps:
[0046] S1, dissolving the loaded drug in water to obtain solution A, dissolving the polymer material capable of ion exchange and the natural polymer material in solution A to obtain solution B and solution C, respectively, stirring and mixing solution B and solution C, and ultrasonically treating solution B and solution C to obtain a mixed solution;
[0047] S2, dissolving a material containing multivalent metal cations in water to obtain a solution D;
[0048] S3. Inject the mixed solution dropwise into solution D, let stand, filter, and wash with water to obtain an oral gastric volume-occupying super absorbent hydrogel.
[0049] In fact, when executing step S1, the following sub-steps are included:
[0050] S1.1. Dissolve white lentil polysaccharide in distilled water at a concentration of (2-10) mg / mL to prepare solution A;
[0051] S1.2, dissolving sodium alginate at (20-40) mg / mL in solution A to obtain solution B, and dissolving inulin at (50-400) mg / mL in solution A to obtain solution C;
[0052] S1.3. Mix solution B and solution C in a volume ratio of 1:(0.5-1.5) and then perform ultrasonic treatment to obtain a mixed solution.
[0053] In some embodiments, when performing step S2, the concentration of the material containing multivalent metal cations in the solution D is (0.1-0.2) mol / L.
[0054] In some embodiments, when executing step S3, the inner diameter of the nozzle of the syringe used for the injection is (1-2) mm.
[0055] In some embodiments, when executing step S3, the standing time is (30-40) min.
[0056] The present invention also provides an application of the oral gastric volume-occupying super absorbent hydrogel in drug loading and targeted delivery and functional health food processing.
[0057] The raw materials used in the embodiments of the present invention are all commercially available, and the reagents used in the performance verification are also commercially available; among them, sodium alginate is sourced from Shanghai MacLean Biochemical Technology Co., Ltd.; inulin is sourced from Shanghai Aladdin Biotechnology Co., Ltd.; and anhydrous calcium chloride is sourced from Shanghai Yuanye Biotechnology Co., Ltd.
[0058] Example 1
[0059] Embodiment 1 of the present invention provides a method for preparing an oral gastric volume-occupying super absorbent hydrogel, comprising the following steps:
[0060] S1.1, dissolve 20 mg of white bean polysaccharide in 10 mL of distilled water to prepare solution A;
[0061] S1.2, dissolve 100 mg of sodium alginate in 5 mL of solution A to obtain solution B, and dissolve 1000 mg of inulin in 5 mL of solution A to obtain solution C;
[0062] S1.3, after 5 mL of solution B and 5 mL of solution C are mixed evenly, excess bubbles are removed by ultrasonication to obtain a mixed solution;
[0063] S2, dissolve 5.549 g (0.05 mol) of calcium chloride in 500 mL of distilled water to prepare solution D;
[0064] S3. The mixed solution is dripped into solution D through a 2 mm syringe, and after standing for 30 minutes, filtered and washed with water to obtain an oral gastric volume super absorbent hydrogel.
[0065] Example 2
[0066] Example 2 of the present invention provides a method for preparing an oral gastric volume-occupying super absorbent hydrogel, which is different from Example 1 in that 750 mg of inulin is added in step S1.2.
[0067] Example 3
[0068] Example 3 of the present invention provides a method for preparing an oral gastric volume-occupying super absorbent hydrogel, which is different from Example 1 in that 500 mg of inulin is added in step S1.2.
[0069] Example 4
[0070] Example 4 of the present invention provides a method for preparing an oral gastric volume-occupying super absorbent hydrogel, which is different from Example 1 in that 250 mg of inulin is added in step S1.2.
[0071] Example 5
[0072] Example 5 of the present invention provides a method for preparing an oral gastric volume-occupying super absorbent hydrogel, which is different from Example 1 in that inulin is not added in step S1.2.
[0073] Performance Testing
[0074] 1. Verification of hydrogel formation by direct observation
[0075] A total of 10 groups of hydrogels containing white lentil polysaccharides, sodium alginate and inulin at different concentrations were prepared. The specific parameters are shown in Table 1. The hydrogels with different proportions were named K0, K5, K10, K15, K20, Z0, Z5, Z10, Z15 and Z20, respectively. Group K was a blank hydrogel without white lentil polysaccharide loading, and group Z was a hydrogel loaded with white lentil polysaccharide. The finished hydrogels were as shown in Figure 1 As shown, the formation of hydrogel microbeads was directly observed by naked eyes;
[0076] See also Figure 1 , Na in the G unit of sodium alginate + With Ga in anhydrous calcium chloride solution 2+ During ion exchange, the G units of sodium alginate are continuously stacked to form a cross-linked network structure, which gives the hydrogel good mechanical properties.
[0077] Table 1 Preparation parameters of hydrogels with different ratios
[0078]
[0079] 2. Fourier transform infrared spectroscopy (FT-IR)
[0080] Infrared spectroscopy was performed on the sodium alginate, inulin, white bean polysaccharide and the prepared oral gastric volume super absorbent hydrogel used in Examples 1 to 5. The results are as follows: Figure 2 As shown, a, b, c, d, e, f, g, and h in Figure A represent inulin (IA), sodium alginate (SA), white hyacinth bean polysaccharide (WHBP), K0, K5, K10, K15, and K20, respectively; a, b, c, d, e, f, g, and h in Figure B represent IA, SA, WHBP, Z0, Z5, Z10, Z15, and Z20, respectively.
[0081] 3. Determination of the physicochemical properties of hydrogels
[0082] (1) Determination of hydrogel surface morphology
[0083] The overall appearance and surface of the above-mentioned hydrogels with different formulations (K0, K5, K10, K15, K20, Z0, Z5, Z10, Z15, and Z20) were characterized by scanning electron microscopy (SEM) to explore the effect of inulin addition on the shape and structure of sodium alginate hydrogel microspheres, thereby improving their mechanical properties as a delivery system. The results are as follows Figure 3 As shown;
[0084] See also Figure 3From the 30× SEM image, it can be found that during the freeze-drying process, the hydrogel microbeads collapsed to a certain extent due to the volatilization of water vapor, and the regular spherical shape of the hydrogel microbeads before freeze-drying could not be maintained, and wrinkles appeared on the surface. Compared with the pure sodium alginate hydrogel microbeads, the hydrogel microbeads with inulin added had a rounder shape, smaller surface wrinkles, and a lower degree of collapse of the spherical structure, indicating that inulin can enhance the anti-collapse ability of the hydrogel microbeads; at the same time, by comparing the blank hydrogel after freeze-drying with the hydrogel without inulin added, it can be found that the addition of white hyacinth bean polysaccharide enables the hydrogel microbeads to better maintain their original spherical shape, and the surface wrinkles become smaller and more uniform, which has a similar effect to inulin. This may be because inulin and white hyacinth bean polysaccharide are both polysaccharides; the 400× and 1000× SEM images show that the surface structure of the freeze-dried hydrogel microbeads is complete and smooth, and the freeze-drying process does not cause damage to the surface structure of the hydrogel microbeads, indicating that freeze-drying is an effective method for preserving hydrogel microbeads.
[0085] (2) Determination of water content of hydrogel
[0086] The above hydrogels (K0, K5, K10, K15, K20, Z0, Z5, Z10, Z15, Z20) were dried in an oven at 37°C until the weight no longer changed. The water content of each group of hydrogels was measured. The results are as follows: Figure 4 As shown;
[0087] The results showed that the water content of each group of hydrogels was above 90%, among which the pure alginate hydrogel microbeads had the highest water content, up to 96.51%, while the water content of the microbeads containing inulin decreased with the increase of inulin content; this phenomenon can be explained by the different densities in the formed microsphere network, which affects the affinity between water and polymer.
[0088] (3) Determination of hydrogel water absorption and swelling properties
[0089] Take 20 mg of freeze-dried hydrogel (K0, K5, K10, K15, K20, Z0, Z5, Z10, Z15, Z20) and put it into 5 mL of distilled water. Place it in a shaker at 37°C and 100 r / min until its weight no longer changes. Record its weight and convert it into swelling rate (%). The results are as follows: Figure 5 As shown;
[0090] The swelling performance of each group of hydrogels was tested, and it can be clearly observed that the swelling performance of the hydrogel showed a significant change with the addition of inulin. As shown in Figure A, with the addition of inulin, the swelling performance of the freeze-dried drug-loaded hydrogel microbeads improved. When the inulin content was 10%, the swelling rate reached the highest, and after the inulin content exceeded 10%, the swelling rate began to decrease, indicating that the improvement of the swelling performance of the sodium alginate hydrogel microbeads by inulin was non-quantity-dependent. The reason for this phenomenon may be that excessive inulin will destroy the dense network structure of the hydrogel, making it unable to retain too much water, or excess inulin will block the gaps in the hydrogel network structure, making it impossible for the water to be fully absorbed.
[0091] Empty hydrogels with different proportions were set as the control group to further verify the effect of inulin content on the swelling properties of hydrogels, and the effect of WHBP on the swelling properties of hydrogels was explored. The results are shown in Figure B. It was found that the trend of the swelling properties of hydrogels changing with inulin content was basically consistent with Figure A, but the one with the highest swelling rate was K5. In addition, by comparing Figure A and Figure B, it can be found that among the hydrogels with the same inulin ratio, the swelling properties of the hydrogels loaded with WHBP are better than those of the empty hydrogels. The addition of WHBP improves the overall swelling properties of the hydrogel microbeads, indicating that the addition of WHBP not only acts as a bioactive substance, but also improves the swelling properties of the hydrogels.
[0092] (4) Determination of hydrogel encapsulation efficiency
[0093] 0.5 g of the hydrogels prepared in Examples 1 to 5 were dissolved in 3.5 mL of 2% (w / v) sodium citrate solution, and mixed evenly on a shaker at 37°C and 100 r / min to completely dissolve. An appropriate amount of the solution was taken to measure the absorbance at 274 nm (maximum absorption wavelength), and the content of WHBP in the microbeads was determined in combination with the standard curve, and the encapsulation efficiency was calculated by the formula. The results are as follows: Figure 6 As shown, the encapsulation efficiencies of the drug-loaded hydrogels were measured to be 20.3%, 26.8%, 49.9%, 44.0%, and 37.8%, respectively;
[0094] The results showed that the overall encapsulation efficiency of the hydrogel microbeads was not particularly high, which may be due to the hydrophilicity of white bean polysaccharides, which quickly diffused into the calcium chloride solution during the gelation process; the encapsulation efficiency of pure sodium alginate hydrogel was low. After adding inulin, the encapsulation efficiency of the microbeads was improved. This may be due to the high viscosity of the solution, which led to a strong interaction between alginate and inulin, resulting in an increase in the encapsulation rate, but excessive inulin will lead to a decrease in the encapsulation efficiency, even lower than that of pure sodium alginate hydrogel; sodium alginate hydrogels are usually porous, so compounding sodium alginate with other materials can fill the gaps and improve the encapsulation efficiency. However, when this combined carrier is excessive, it will hinder the formation of the hydrogel and reduce the encapsulation efficiency.
[0095] (5) In vitro digestion experiment of hydrogel
[0096] The in vitro digestion model was constructed according to the INFOGEST 2.0 protocol, an international protocol for in vitro digestibility testing, and included the following steps:
[0097] First, 1.25× simulated oral digestive fluid (SSF), simulated gastric fluid (SGF), and simulated intestinal fluid (SIF) stock solutions were prepared for use; in order to more effectively adjust the pH during the digestion stage, a duplicate tube was prepared with the corresponding amount of food, enzymes, and bile during the entire digestion process (pH-test adjustment experiment), and the volume of HCl and NaOH used to reach the target pH was measured and recorded. These volumes are the necessary volumes of acid and alkali required to adjust the pH value of the gastric and intestinal stages during the formal experiment;
[0098] Preheat the SSF stock solution to 37°C, add 0.5 g of hydrogel and 0.8 mL of SSF into a centrifuge tube and mix; add an appropriate amount of anhydrous calcium chloride solution to make the total concentration of anhydrous calcium chloride in SSF reach 1.5 mmol / L; add the remaining water to reach 1× concentration of SSF; incubate the digestion mixture in a shaker at 37°C and 150 r / min for 2 min; separate the solid and liquid in the centrifuge tube to terminate the digestion; weigh the solid and observe the change in the mass of the hydrogel after digestion;
[0099] Preheat the SGF stock solution to 37°C, take 1.6mL of SGF stock solution and add it to the oral stage food, add an appropriate amount of anhydrous calcium chloride solution to make the final SGF concentration 0.15mmol / L; add SGF to 0.4mL of pepsin solution prepared in distilled water to make it reach 2000U / mL activity in the final digestion mixture; add distilled water to reach 1× concentration of SGF; add HCl determined in advance in the pH test adjustment experiment to make up the volume and adjust the pH to 3.0; starting from the point of adding pepsin, incubate the digestion mixture at 37°C and 150r / min in a shaker for 2h; verify the pH during the experiment and adjust it to 3.0 if necessary, take samples every 30min, and process them as above;
[0100] Preheat the SIF stock solution to 37°C, add 3.2 mL of SIF stock solution to the gastric chyme, add the bile solution to the SIF+gastric chyme mixed solution to make the final concentration 10 mmol / L; place the solution in a rotating wheel mixer at 37°C for 30 min to achieve complete dissolution of bile; add an appropriate amount of anhydrous calcium chloride solution to SIF to make its concentration reach 0.6 mmol / L; add 0.4 mL of pancreatic enzyme suspension to the SIF+gastric chyme mixed solution to make the pancreatic enzyme activity (based on trypsin) in the final mixed solution reach 100 U / mL; add distilled water to reach 1× concentration of SI, add NaOH determined in advance in the pH test adjustment experiment to make up the volume, and adjust the pH to 7.0; starting from the time of adding pancreatic enzyme, incubate the digestion mixture at 37°C and 150 r / min in a shaker for 2 h; verify the pH during the experiment and adjust it to 7.0 if necessary, take samples every 30 min, and treat them in the same way as above;
[0101] The results are as follows Figures 7 to 9 As shown, Figure 7 and Figure 8 These are the digestion behavior test graphs and digestion expansion rate statistics of hydrogels with different proportions. Figure 7 and Figure 8 It shows that pure sodium alginate hydrogel microbeads were not degraded by digestive juice and digestive enzymes during the whole digestion experiment, and a large amount of free water filled the void area of the hydrogel network, which was manifested as the microbeads absorbing water and swelling; Fig. 9 The real-time record of the hydrogel microbeads during the digestion process shows an obvious increase in volume. At the same time, it can be observed that with the addition of inulin, the water absorption and expansion capacity of the hydrogel microbeads increases. However, when the amount of inulin exceeds a certain value, the water absorption and expansion capacity of the hydrogel microbeads begins to weaken, and is even weaker than that of pure sodium alginate hydrogel microbeads. This may be because excessive inulin will block the pores of the hydrogel and hinder the water absorption and expansion of the hydrogel. The 5% inulin hydrogel microbeads have the strongest water absorption and expansion capacity during the digestion process. In addition, the digestion behavior of group Z during the digestion process was analyzed and compared with group K. It was found that the change trend of its expansion rate was roughly consistent with that of group K.
[0102] at the same time Figure 7 and Figure 8 It shows that the swelling rate of hydrogel microbeads in SGF (acidic environment) is low, and the swelling rate of microbeads increases sharply after being transferred to SIF. Figure 5 This phenomenon can also be observed in real-time photos of microbeads; the surface structure of alginate hydrogel shrinks in a low pH environment, making it difficult for water to penetrate into the beads; in addition, sodium alginate is a hydrophilic polysaccharide. Due to the presence of -OH and -COOH groups in its chain, this property enables sodium alginate to react with the positively charged ions Ca in calcium chloride during the hardening process. 2+Cross-linking; in neutral and weakly alkaline environments, free water can form hydrogen bonds through -OH and -COOH groups and fill the hydrogel gaps along the chains.
[0103] (6) Drug controlled release experiment of hydrogel
[0104] 0.3 g of microbeads were suspended in 4 mL of distilled water and stirred continuously on a shaker at 100 rpm; 200 μL aliquots were taken every 30 min for analysis, and the results were expressed in mg / mL; in addition, release studies were also conducted under SGF (pH 3.0) and SIF (pH 7.0) conditions, where the microbeads were immersed in SGF, decanted after 2 h and transferred to SIF solution; then, the aliquots were submitted to a UV-Vis spectrophotometer, the absorbance was read at 274 nm (highest absorption peak), and converted to concentration based on the standard curve, and the results are shown in Fig.10 As shown;
[0105] See also Fig.10 The results showed that only a very small amount of WHBP in the hydrogel was released, and its maximum release amount did not exceed 10% in either distilled water or simulated digestive fluid, that is, the retention rate of bioactive substances in the hydrogel microbeads was as high as over 90%, which had a very good protective effect on the encapsulated bioactive substances; in addition, the in vitro simulated digestion experiment confirmed that the hydrogel microbeads prepared in this study were resistant to digestion and degradation. Combined with the characteristics of sodium alginate and inulin being decomposed by specific bacterial secretions in the intestine, this hydrogel microbead can achieve the function of enriching bioactive ingredients and targeted intestinal release.
[0106] Although the embodiments of the present invention are described in detail above, it is obvious to those skilled in the art that various modifications and variations can be made to these embodiments. However, it should be understood that such modifications and variations are within the scope and spirit of the present invention as described in the claims. Moreover, the present invention described herein may have other embodiments and may be implemented or realized in a variety of ways.
Claims
1. An oral gastric volume super absorbent hydrogel, characterized in that: The hydrogel comprises a polymer material capable of ion exchange, a natural polymer material, a material containing multivalent metal cations and loaded drugs.
2. The hydrogel according to claim 1, characterized in that The polymer material capable of ion exchange includes sodium alginate; the natural polymer material includes at least one of inulin, collagen, chitosan, xanthan gum and gelatin; the metal cations in the material containing multivalent metal cations include Zn 2+ , Fe 3+ , Ba 2+ Cr 3+ and Ca 2+ At least one of the following; the loaded drug includes white bean polysaccharide.
3. A method for preparing an oral gastric volume-occupying superabsorbent hydrogel, characterized in that: The following steps are involved: S1, dissolving the loaded drug in water to obtain solution A, dissolving the polymer material capable of ion exchange and the natural polymer material in solution A to obtain solution B and solution C, respectively, stirring and mixing solution B and solution C, and ultrasonically treating solution B and solution C to obtain a mixed solution; S2, dissolving a material containing a multivalent metal cation in water to obtain a solution D; S3. Inject the mixed solution dropwise into solution D, let stand, filter, and wash with water to obtain an oral gastric volume-occupying super absorbent hydrogel.
4. The preparation method according to claim 3, characterized in that: In step S1: the concentration of the loaded drug in the solution A is (2-10) mg / mL; the concentration of the polymer material capable of ion exchange in the solution B is (20-40) mg / mL; the concentration of the natural polymer material in the solution C is (50-400) mg / mL; and the volume ratio of the solution B to the solution C is 1:(0.5-1.5).
5. The preparation method according to claim 3, characterized in that: The concentration of the material containing multivalent metal cations in the solution D in step S2 is (0.1-0.2) mol / L.
6. The preparation method according to claim 3, characterized in that: In step S3: the inner diameter of the nozzle of the syringe used for the injection is (1-2) mm; the standing time is (30-40) min.
7. Use of the hydrogel according to any one of claims 1 to 2, or the hydrogel prepared by the preparation method according to any one of claims 3 to 6 in drug loading and targeted delivery and functional health food processing.