Drinkable drug-loaded hydrogel for intestinal tract treatment and application of drinkable drug-loaded hydrogel

Abstract

The invention discloses a drinkable drug-loaded hydrogel for intestinal tract treatment and application, the drinkable drug-loaded hydrogel comprises a cross-linking agent and a polymer solution, the cross-linking agent is an edible calcium ion solution, the polymer solution comprises alginate, polyethylene glycol, sericin and a treatment drug, and the drinking sequence is that the cross-linking agent is firstly drunk, and the polymer solution is later drunk. According to the present invention, the water absorption performance is excellent, the drug loading capacity is high, and the chemical property is stable. When the hydrogel is applied to the treatment of intestinal ulcer, the characteristics of the hydrogel are fully exerted, specifically, the hydrogel takes effect quickly, the medicinal duration is long, the hydrogel can effectively promote spatial proximity of a drug and a cross-linking agent, regulate drug release or protect drug activity from being influenced by a severe intestinal environment, and the intestinal residence time of a drug library is prolonged. The adopted materials are wide in source and relatively low in cost, the manufacturing method is simple, convenient and easy to implement, and large-scale industrial production is extremely easy to achieve.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, in particular to a drinkable drug-loaded hydrogel for intestinal treatment and application thereof. Background Art

[0002] The oral route offers a safe, rapid, and easy administration process for drug delivery, with greater patient comfort and compliance compared to the enteral route. Oral solid drugs have become the dominant formulation due to advantages in stability, dose consistency, and the ability to be co-formulated with cross-linkers. However, certain patient populations have difficulty swallowing solids. While liquid formulations are easier to ingest, they are prone to rapid dilution in the intestine and the inability to spatially localize the drug with cross-linkers poses challenges for oral biologic drugs. Summary of the invention

[0003] Systems that can perform programmed liquid-to-solid transformations in the intestine can overcome the above-mentioned problems of the prior art. The solid matrix promotes spatial proximity between drugs and crosslinkers, regulates drug release or protects drug activity from the harsh intestinal environment, and increases the intestinal residence time of the drug library. Therefore, the development of drinkable drug-loaded hydrogels for the treatment of intestinal diseases is of great significance.

[0004] The present invention provides such a drinkable drug-loaded hydrogel for intestinal treatment, comprising a cross-linking agent and a polymer solution, wherein the cross-linking agent is an edible calcium ion solution, and the polymer solution comprises alginate, polyethylene glycol (CAS: 25322-68-3), sericin (CAS: 60650-89-7) and a therapeutic drug, and the order of drinking is the cross-linking agent first and the polymer solution later. The alginate is preferably sodium alginate (CAS: 9005-38-3).

[0005] Preferably, the concentration of the edible calcium ion solution is 3% to 6% by weight.

[0006] Preferably, the edible calcium ion solution is a calcium chloride solution, or may be other divalent calcium ion solutions.

[0007] Preferably, the drinkable drug-loaded hydrogel comprises 10-20 parts of edible calcium ion solution and 25-50 parts of polymer solution by weight.

[0008] In some embodiments, the polymer solution includes 10-20 parts of alginate, 2-5 parts of polyethylene glycol, 1-3 parts of sericin and 10-25 parts of therapeutic drugs by weight. The synthesis process of the polymer solution includes: mixing the alginate, polyethylene glycol, sericin and therapeutic drugs according to the above proportions, heating and stirring until the mixed solution is uniform.

[0009] Furthermore, the interval between taking the edible calcium ion solution and the polymer solution is no more than 30 minutes.

[0010] The present invention also provides application of the drinkable drug-loaded hydrogel for intestinal treatment in improving intestinal ulcers.

[0011] The present invention has the following beneficial effects: the drinkable drug-loaded hydrogel for intestinal treatment of the present invention exhibits excellent water absorption performance, high drug loading and stable chemical properties. When the hydrogel is used for the treatment of intestinal ulcers, its characteristics are fully utilized, specifically manifested in rapid onset, long duration of medicinal use, and can effectively promote the spatial proximity of drugs and cross-linking agents, regulate drug release or protect drug activity from the influence of harsh intestinal environment, and increase the intestinal residence time of the drug library. The materials used in the present invention have a wide range of sources and are relatively low in cost. The preparation method thereof is simple and easy, and it is very easy to realize large-scale industrial production. Compared with the prior art, the drinkable drug-loaded hydrogel of the present invention provides cost control and high biosafety, and is more targeted for intestinal treatment. DETAILED DESCRIPTION

[0012] In order to enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work should fall within the scope of protection of the present application.

[0013] It should be noted that the terms "include" and "have" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or apparatus comprising a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to these processes, methods, products or apparatus.

[0014] As mentioned in the background, some patient populations have difficulty swallowing solids. While liquid formulations are easier to ingest, they are prone to rapid dilution in the intestine and the inability to spatially localize the drug with a cross-linker has challenged efforts to deliver oral biopharmaceuticals. Systems that enable programmed liquid-to-solid transformations in the intestine could bridge the advantages of both formats. Solid matrices could facilitate spatial proximity of the drug and cross-linker, modulate drug release or protect drug activity from the harsh intestinal environment, and increase intestinal residence time of the drug depot.

[0015] Hydrogel is a hydrophilic polymer network system with a unique three-dimensional structure. Its characteristic is that it can absorb water and swell in aqueous solution while remaining insoluble, making it suitable as a drug carrier in the medical field. Therefore, the development of drinkable drug-loaded hydrogels for the treatment of intestinal diseases is of great significance, more appropriate, and easy to promote.

[0016] The present invention provides an embodiment of a drinkable drug-loaded hydrogel for intestinal treatment. The drinkable drug-loaded hydrogel comprises a cross-linking agent and a polymer solution, wherein the cross-linking agent is an edible calcium ion solution, and the polymer solution comprises alginate, polyethylene glycol (CAS: 25322-68-3), sericin (CAS: 60650-89-7) and a therapeutic drug, wherein the alginate is preferably sodium alginate (CAS: 9005-38-3). The order of drinking is cross-linking agent first, and polymer solution later.

[0017] The administration method of this embodiment is: first take the cross-linking agent orally, and then take the polymer solution composed of alginate, polyethylene glycol, sericin and therapeutic drugs orally after a period of time. The polymer solution contacts the cross-linking agent in the intestine to form a drug-loaded hydrogel.

[0018] As a preferred embodiment, the interval between oral administration of the crosslinking agent and the polymer solution is no more than 30 minutes.

[0019] The cross-linking agent is an edible calcium ion solution, usually a calcium chloride solution, or other divalent calcium ion solutions.

[0020] Furthermore, the concentration of the edible calcium ion solution is 3% to 6% by weight, that is, w% = (solute mass / solution mass) × 100%.

[0021] The drinkable drug-carrying hydrogel comprises 10 to 20 parts of edible calcium ion solution and 25 to 50 parts of polymer solution by weight.

[0022] The polymer solution further comprises 10-20 parts of alginate, 2-5 parts of polyethylene glycol, and 1-3 parts of sericin by weight. The synthesis process of the polymer solution comprises: mixing the alginate, polyethylene glycol, and sericin according to the above proportions, and heating and stirring until the mixed solution is uniform.

[0023] Generally, in terms of administration, the therapeutic drug can be mixed with the polymer solution in the drug-loaded hydrogel. For example, the therapeutic drug can be trypsin, which is used to decompose and thin pus and blood clots, make drainage smooth, and promote wound healing. The weight portion can be 10 to 25 parts.

[0024] It should be noted that the interval between taking the edible calcium ion solution and the polymer solution should not exceed 30 minutes.

[0025] The present invention also provides application of the drinkable drug-loaded hydrogel for intestinal treatment in improving intestinal ulcers.

[0026] Example 1

[0027] A drinkable drug-loaded hydrogel for intestinal treatment comprises a cross-linking agent and a polymer solution, wherein the cross-linking agent is an edible calcium ion solution, and the polymer solution comprises sodium alginate (CAS: 9005-38-3), polyethylene glycol (CAS: 25322-68-3), sericin (CAS: 60650-89-7) and a therapeutic drug. The cross-linking agent is preferably a calcium chloride solution.

[0028] Specifically, the composition comprises, by weight, 10 to 20 parts of sodium alginate, 2 to 5 parts of polyethylene glycol, 1 to 3 parts of sericin, 10 to 20 parts of CaCl2 solution, and 10 to 25 parts of trypsin.

[0029] The synthesis process of the polymer solution includes: mixing the sodium alginate, polyethylene glycol, sericin and trypsin in the above weight parts, and heating and stirring until the mixed solution is uniform.

[0030] The administration method of the prepared drinkable drug-loaded hydrogel is: first take the CaCl2 solution orally, and then take the polymer solution orally within 30 minutes.

[0031] Intestinal drug sustained release animal model experiment 1 1. Experimental animals: 60 male Sprague Dawley rats weighing 150-180 g were selected.

[0032] 2. Experimental materials: Drinkable drug-loaded hydrogel prepared according to the weight ratio described in this example.

[0033] 3. Experimental grouping: 60 rats were randomly divided into 3 experimental groups, blank group (n=15), no crosslinking agent group (n=15), hydrogel low loading group (n=15), hydrogel high loading group (n=15). The drug loading of the low loading group was 5% - 20% (w / w), and the drug loading of the high loading group was 30% - 50% (w / w). Blood was collected from rats every hour, plasma was separated, and the drug concentration in plasma, that is, the amount of drug released, was detected.

[0034] 4. Experimental Results

[0035] The results showed that the composition used in this experimental example had a sustained-release effect of the drug and the high-dose group had the best effect.

[0036] Example 2

[0037] A drinkable drug-loaded hydrogel for intestinal treatment comprises a cross-linking agent and a polymer solution, wherein the polymer solution comprises sodium alginate (CAS: 9005-38-3), polyethylene glycol (CAS: 25322-68-3), sericin (CAS: 60650-89-7) and a therapeutic drug. The cross-linking agent is preferably a calcium chloride solution.

[0038] Specifically, the composition comprises, by weight, 10 to 20 parts of sodium alginate, 2 to 5 parts of polyethylene glycol, 1 to 3 parts of sericin, 10 to 20 parts of CaCl2 solution, and 10 to 25 parts of lactobacillus.

[0039] The synthesis process of the polymer solution includes: mixing the sodium alginate, polyethylene glycol, sericin and lactobacillus in the above weight parts, and heating and stirring until the mixed solution is uniform.

[0040] The administration method of the prepared drinkable drug-loaded hydrogel is: first take the CaCl2 solution orally, and then take the polymer solution orally within 30 minutes.

[0041] Intestinal drug sustained release animal model experiment 2 1. Experimental animals: 60 male Sprague Dawley rats weighing 150-180 g were selected.

[0042] 2. Experimental materials: Drinkable drug-loaded hydrogel prepared according to the weight ratio described in this example.

[0043] 3. Experimental grouping: 60 rats were randomly divided into 3 experimental groups, blank group (n=15), no crosslinking agent group (n=15), hydrogel low loading group (n=15), hydrogel high loading group (n=15). The drug loading of the low loading group was 5% - 20% (w / w), and the drug loading of the high loading group was 30% - 50% (w / w). Blood was collected from rats every hour, plasma was separated, and the drug concentration in plasma, that is, the amount of drug released, was detected.

[0044] 4. Experimental Results

[0045] The results showed that the compositions used in this experimental example all had the effect of sustained drug release and the high-dose group had the best effect.

[0046] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A drinkable drug-loaded hydrogel for intestinal treatment, characterized in that: It includes a cross-linking agent and a polymer solution, wherein the cross-linking agent is an edible calcium ion solution, and the polymer solution includes alginate, polyethylene glycol, sericin and therapeutic drugs. The order of drinking is the cross-linking agent first and the polymer solution later.

2. The drinkable drug-loaded hydrogel for intestinal treatment according to claim 1, characterized in that: The concentration of the edible calcium ion solution is 3% to 6% by weight.

3. The drinkable drug-loaded hydrogel for intestinal treatment according to claim 2, characterized in that: The edible calcium ion solution is a calcium chloride solution.

4. The drinkable drug-loaded hydrogel for intestinal treatment according to claim 3, characterized in that: The drinkable drug-carrying hydrogel comprises 10 to 20 parts of edible calcium ion solution and 25 to 50 parts of polymer solution by weight.

5. The drinkable drug-loaded hydrogel for intestinal treatment according to claim 1, characterized in that: The polymer solution is prepared by the following production process, including mixing 10-20 parts of the alginate, 2-5 parts of the polyethylene glycol, 1-3 parts of the sericin and 10-25 parts of the therapeutic drug in parts by weight, and heating and stirring until the mixed solution is uniform.

6. The drinkable drug-loaded hydrogel for intestinal treatment according to claim 1, characterized in that: The interval between taking the edible calcium ion solution and the polymer solution is no more than 30 minutes.

7. Use of the drinkable drug-loaded hydrogel for intestinal treatment according to any one of claims 1 to 6 in improving intestinal ulcers.

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