Sodium alginate-chitosan compound for improving glucose and lipid metabolism disorder and preparation method of sodium alginate-chitosan compound

Abstract

The invention discloses a sodium alginate-chitosan compound for improving glucose and lipid metabolism disorder and a preparation method thereof, relates to the technical field of sodium alginate and chitosan, and aims to solve the problem of providing the sodium alginate-chitosan compound, the sodium alginate-chitosan compound comprises 50%-70% of sodium alginate and 30%-50% of chitosan.

Description

Technical Field

[0001] This invention relates to the technical field of sodium alginate and chitosan, and specifically to a sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders. Background Technology

[0002] With changes in dietary structure, disorders of glucose and lipid metabolism, such as obesity, hyperglycemia, hyperlipidemia, and insulin resistance caused by high-fat diets, have become a global public health problem. While existing medications such as metformin and statins are effective, long-term use may be accompanied by side effects such as gastrointestinal reactions and liver and kidney damage, and patient adherence is poor.

[0003] Therefore, developing safe, effective, and naturally derived functional foods or adjuvant therapies is of great significance. Sodium alginate and chitosan are both natural polysaccharides with good biocompatibility and biodegradability. Sodium alginate, due to its gelling and adsorption properties, has been studied for its ability to delay sugar absorption and increase satiety; chitosan, due to its cationic properties, has been shown to bind dietary lipids and bile acids, promoting their excretion. However, current technologies mostly focus on the application of single components, with limited effects and simple mechanisms of action. Theoretically, combining anionic sodium alginate with cationic chitosan could form a more stable system through electrostatic interactions, potentially producing a synergistic effect of "1+1>2." However, current technologies do not provide clear guidance or solutions regarding the systemic regulatory effect of their specific ratio on occipital bone glucose and lipid metabolism.

[0004] Therefore, it is very necessary to provide a sodium alginate-chitosan complex that can effectively improve glucose and lipid metabolism disorders induced by high-fat diets, reduce blood sugar and blood lipids, and improve insulin sensitivity through synergistic effects, and is natural, safe, and has few side effects. Summary of the Invention

[0005] The present invention aims to solve the problem of providing a sodium alginate-chitosan complex, and proposes a sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders, which comprises 50%-70% sodium alginate and 30%-50% chitosan by mass percentage.

[0006] A further provision of the present invention is that the composite contains less than 10% by weight of excipients; wherein the excipients include fillers and lubricants.

[0007] A further feature of the present invention is that the ratio of sodium alginate to chitosan is selected as 5:5.

[0008] A further provision of the present invention is that the filler is selected as microcrystalline cellulose and the lubricant is selected as magnesium stearate.

[0009] This invention also proposes a method for preparing the sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders as described above, comprising the following steps: S1: Raw material dissolution: Dissolve the sodium alginate in deionized water and stir until completely dissolved to obtain a sodium alginate solution; dissolve the chitosan in a 1% acetic acid solution and stir until clear to obtain a chitosan solution; S2: Composite reaction, under continuous stirring, the chitosan solution is slowly added dropwise to the sodium alginate solution, and the pH of the reaction system is adjusted to 4.0-5.0 using NaOH or HCl solution; S3: Curing and aging. After the reaction is complete, continue to stir gently for 0.6 hours to ensure the composite reaction is complete. S4: Solid-liquid separation, centrifugation to collect the complex precipitate, and washing twice with deionized water to remove residual acetic acid and salt; S5: Drying, using freeze drying;

[0010] S6: Post-processing and formulation: The freeze-dried product is pulverized to obtain sodium alginate-chitosan complex powder, and the excipients are added to it and mixed. After mixing, it is directly filled into capsules or compressed into tablets.

[0011] The beneficial effects of this invention are as follows: by using a specific ratio of sodium alginate and chitosan and an optimized preparation process, a sodium alginate-chitosan complex with synergistic effects can be successfully prepared; thereby achieving the effects of synergistically lowering blood lipids, synergistically lowering blood sugar, improving insulin resistance, liver redox state, and comprehensive improvement in vivo. Attached Figure Description

[0012] Figure 1 The graph shows the fasting blood glucose test results in mice.

[0013] Figure 2 The diagram shows the changes in the OGTT experiment during week 7.

[0014] Figure 3 The changes were shown in the OGTT experiment during week 15.

[0015] Figure 4 The AUC comparison between week 7 and week 15 of the OGTT experiment is shown.

[0016] Figure 5 The changes in the ITT experiment during week 8 are shown.

[0017] Figure 6 The changes in the ITT experiment during week 16 are shown.

[0018] Figure 7 The AUC comparison between week 8 and week 16 of the ITT experiment is shown.

[0019] Figure 8 The TG index is shown.

[0020] Figure 9 The TC indicator is shown.

[0021] Figure 10 The HDL-C index is shown.

[0022] Figure 11 The LDL-C index is shown.

[0023] Figure 12 HE staining of liver tissue in the NF group is shown.

[0024] Figure 13 HE staining of the liver in the HF group is shown.

[0025] Figure 14 HE staining of the liver in the HF+CTS group is shown.

[0026] Figure 15 HE staining of the liver in the HF+SA group is shown.

[0027] Figure 16 HE staining of the liver in the HF+CTS+SA group is shown. Detailed Implementation

[0028] Those skilled in the art can refer to the content of this document and appropriately improve the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can make modifications or appropriate alterations and combinations to the methods and applications described herein without departing from the content, spirit, and scope of this invention to implement and apply the technology of this invention.

[0029] Example 1

[0030] This invention proposes a sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders, comprising, by mass percentage, 50%-70% sodium alginate (SA) and 30%-50% chitosan (CTS).

[0031] The complex also contains less than 10% by weight of excipients, including fillers and lubricants.

[0032] The ratio of sodium alginate to chitosan was selected as 5:5.

[0033] The filler was selected as microcrystalline cellulose, and the lubricant was selected as magnesium stearate, both of which are pharmaceutical excipients.

[0034] The effects and principles of each component are as follows:

[0035] Sodium alginate: forms a gel in the acidic environment of the stomach, slowing gastric emptying and increasing satiety; its viscous binding properties can physically encapsulate glucose and fat in food, delaying their absorption in the small intestine. Its molecular chain contains carboxyl groups (…). - COO - It can interact with water molecules and food components to form a three-dimensional network structure.

[0036] Chitosan: Due to its cationic properties, it strongly adsorbs and integrates negatively charged bile acids, cholesterol, and fats to form insoluble complexes that are excreted with feces, thereby blocking enterohepatic circulation and lowering blood lipids. The amino group (-NH3) on the molecular chain is protonated in acidic to neutral environments and combines with negatively charged substances through electrostatic interactions.

[0037] Sodium alginate-chitosan ionic complex: Sodium alginate - COO - A polyelectrolyte complex is formed through electrostatic interaction with the -NH3 group of chitosan. This complex combines the properties of both: it can form a gel in the stomach to delay gastric emptying, and it can more effectively capture fat droplets, bile acids, and glucose molecules in the intestinal environment. This composite structure may have a larger specific surface area and more stable adsorption properties than physical mixtures, thus producing a synergistic effect in lowering blood sugar and lipids.

[0038] Example 2

[0039] A method for preparing a sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders as described in Example 1 includes the following steps:

[0040] S1: Raw material dissolution: Sodium alginate is dissolved in deionized water and stirred until completely dissolved to obtain a sodium alginate solution; chitosan is dissolved in 1% acetic acid solution and stirred until clear to obtain a chitosan solution.

[0041] S2: Composite reaction. Under continuous stirring, the chitosan solution is slowly added dropwise to the sodium alginate solution, and the pH of the reaction system is adjusted to 4.0-5.0 using NaOH or HCl solution.

[0042] S3: Curing and aging. After the reaction is complete, continue to stir gently for 0.6 hours to ensure the composite reaction is complete.

[0043] S4: Solid-liquid separation, centrifugation to collect the complex precipitate, and washing twice with deionized water to remove residual acetic acid and salt.

[0044] S5: Drying, using freeze drying.

[0045] S6: Post-processing and formulation: The freeze-dried product is pulverized to obtain sodium alginate-chitosan complex powder, and excipients are added and mixed. After mixing, it is directly filled into capsules or compressed into tablets.

[0046] In step S2, the pH range is selected as 4.5 to ensure that the carboxyl groups of sodium alginate are fully ionized. - COO - The amino groups of chitosan are fully protonated (-NH3), driving strong electrostatic interactions to form uniform and stable complex particles or gel particles. If the pH is too low, the chitosan solubility is good, but the sodium alginate is not sufficiently ionized; if the pH is too high, chitosan begins to precipitate, affecting the composite effect.

[0047] In step S5, freeze-drying avoids the degradation of bioactivity caused by high temperatures and maintains the inherent porous network structure of the complex. This porous structure significantly increases the specific surface area, enabling more effective adsorption and containment of lipid and carbohydrate molecules in vivo, thereby improving its bioavailability and efficacy. Spray drying or oven drying may cause structural collapse, affecting the results.

[0048] The compound disclosed in this application is intended for use in individuals or dogs at risk of glucose and lipid metabolism disorders or in the pre-disease stage.

[0049] Recommended dosage: Based on animal data, the recommended daily intake of sodium alginate-chitosan complex for a 60kg adult is 50mg, divided into 1-2 doses before or during meals, to take advantage of its ability to adsorb lipids and sugars in food.

[0050] A sodium alginate-chitosan complex with synergistic effects was successfully prepared using a specific formulation ratio (SA:CTS=5:5) and an optimized preparation process (pH 4.5, freeze-drying). Mouse experiments were conducted, and the achieved technical results are as follows:

[0051] Synergistic lipid-lowering effect: The complex group reduced serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in mice on a high-fat diet by a greater extent than sodium alginate and chitosan alone.

[0052] Synergistic effects in lowering blood sugar and improving insulin resistance: The complex can more effectively reduce fasting blood glucose (FBG) and improve changes in glucose tolerance and abnormal insulin regulation caused by a high-fat diet.

[0053] Liver redox status: The complex group inhibits the degree of biomimetic lipid peroxidation damage to liver tissue caused by a high-fat diet, enhances the activity of antioxidant enzyme (SOD), and has a greater free radical scavenging effect than sodium alginate or chitosan alone.

[0054] Overall in vivo improvement effect: The complex can more significantly reduce hepatic steatosis and reduce lipid deposition in the liver of mice on a high-fat diet.

[0055] Comparative experimental cases

[0056] The experiment was conducted using mice, which were subjected to a high-fat diet for 16 weeks.

[0057] The effects of CTS, SA, and SA-CTS on the body weight of mice on a high-fat diet (n=12 mice per group) are compared in Table 1 below:

[0058] Note: * indicates comparison with group NF; # indicates comparison with group HF; △ indicates comparison with group HF+CTS.

[0059] refer to Figure 1 This is a graph showing the fasting blood glucose levels in mice; for reference. Figure 2 This is a schematic diagram showing the changes in the OGTT experiment during week 7; for reference. Figure 3 Changes to the OGTT week 15 experiment; Reference Figure 4 Comparison of AUC at week 7 and week 15 of the OGTT experiment; Reference Figure 5 This refers to the changes in the ITT experiment during week 8; see reference. Figure 6 This refers to the changes in the ITT experiment during week 16; see reference. Figure 7 The comparison of AUC between week 8 and week 16 of the ITT experiment is shown; where * indicates comparison with the NF group; # indicates comparison with the HF group; ☆ indicates comparison with HF+CTS; and ▲ indicates comparison with the HF+CTS+AOS group.

[0060] contrast Figure 1-7 The effects of CTS and SA on glucose metabolism indicators in high-diet mice can be observed (n=12).

[0061] refer to Figure 8 For reference only (TG indicator). Figure 9 TC indicator; for reference Figure 10 This refers to high-density lipoprotein (HDL-C) levels; reference. Figure 11 The LDL-C index is represented by *, which indicates a comparison with the NF group; # indicates a comparison with the HF group; and ▲ indicates a comparison with the HF+CTS+AOS group.

[0062] contrast Figure 8-11 The effects of CTS and SA on blood lipids in high-diet mice can be observed (n=12).

[0063] The effects of CTS, SA, and SA-CTS on the liver redox status of mice on a high-fat diet (n=12) are compared in Table 2 below:

[0064] Note: * indicates comparison with group NF; # indicates comparison with group HF; △ indicates comparison with group HF+CTS.

[0065] refer to Figure 12 HE staining of liver tissue in the NF group; Reference Figure 13 HE staining of liver tissue from the HF group; Reference Figure 14 HE staining of liver tissue in the HF+CTS group; Reference Figure 15 HE staining of liver tissue in the HF+SA group; Reference Figure 16 HE staining of liver tissue in the HF+CTS+SA group; where * indicates comparison with the NF group; # indicates comparison with the HF group.

[0066] contrast Figure 12-16 This shows the effects of CTS and SA on the liver of mice fed a high-diet diet.

[0067] In summary, this invention, through a specific ratio of sodium alginate and chitosan and an optimized preparation process, can successfully prepare a sodium alginate-chitosan complex with synergistic effects; thereby achieving synergistic effects in lowering blood lipids, lowering blood sugar, improving insulin resistance, liver redox status, and overall in vivo improvement.

[0068] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be within the scope of protection of the present invention.

Claims

1. A sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders, characterized in that, By mass percentage, it includes 50%-70% sodium alginate and 30%-50% chitosan.

2. The sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders according to claim 1, characterized in that, The complex also contains excipients at a concentration of less than 10% of the complex mass; wherein the excipients include fillers and lubricants.

3. The sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders according to claim 1, characterized in that, The ratio of sodium alginate to chitosan is selected as 5:

5.

4. The sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders according to claim 1, characterized in that, The filler is selected as microcrystalline cellulose, and the lubricant is selected as magnesium stearate.

5. A method for preparing a sodium alginate-chitosan complex for improving glucose and lipid metabolism disorders as described in any one of claims 1-4, characterized in that, It includes the following steps: S1: Raw material dissolution: Dissolve the sodium alginate in deionized water and stir until completely dissolved to obtain a sodium alginate solution; dissolve the chitosan in a 1% acetic acid solution and stir until clear to obtain a chitosan solution; S2: In the composite reaction, the chitosan solution is slowly added dropwise to the sodium alginate solution under continuous stirring, and the pH of the reaction system is adjusted to 4.0-5.0 using NaOH or HCl solution. S3: Curing and aging. After the reaction is complete, continue to stir gently for 0.6 hours to ensure the composite reaction is complete. S4: Solid-liquid separation, centrifugation to collect the complex precipitate, and washing twice with deionized water to remove residual acetic acid and salt; S5: Drying, using freeze drying; S6: Post-processing and formulation: The freeze-dried product is pulverized to obtain sodium alginate-chitosan complex powder, and the excipients are added to it and mixed. After mixing, it is directly filled into capsules or compressed into tablets.

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