IPN hydrogel for preparation and application

Abstract

The invention discloses an interpenetrating biopolymers network (IPN) hydrogel loaded with herbal extracts, preparation and application thereof. The IPN hydrogel can increase the preservation time of herbal extracts and achieve a long-term release mechanism of herbal extracts. The interpenetrating biopolymers network (IPN) hydrogel makes itself have microporous and macroporous network structure and reinforced gel structure. The gel itself has good hydrophilicity and high biocompatibility.

In addition, the present invention will be subsequently applied to the development of hydrogel patches and preparation methods, which are composed of bidirectional elastic non-woven fabrics, hydrogels containing extracts and a cover film layer, and solve the common the problem of allergies caused by patches.

Claims

1. An interpenetrating biopolymers network hydrogel comprising: a first polymer layer; a second polymer layer; wherein the first polymer layer and the second polymer layer are respectively formed by polymerizing at least one alkaline treated ethylenically unsaturated monomer, crosslink through a cross-linking agent and a photoinitiator; and the pH value of the hydrogel is 6.5 to 8.

2. The interpenetrating biopolymers network hydrogel according to claim 1, wherein the ethylenically unsaturated monomer is selected from the group consisting of hydroxyethyl acrylate (HEA), hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl acrylate (2-HPA), 2-hydroxypropyl methacrylate (2-HPMA), 3-hydroxypropyl acrylate (3-HPA), 3-hydroxypropyl methacrylate (3-HPMA), acrylic-2,3-dihydroxypropyl ester, 2,3-dihydroxypropyl methacrylate, 1,3-dipropenylglycerol, 1,3-dimethylpropenylglycerol, trimethylolpropane monoacrylate, trimethylolpropane monomethacrylate, trimethylolpropane diacrylate, trimethylolpropane dimethacrylate, 2-propenamido-2-methyl-1-propanesulfonic acid (AMPS), or the combination thereof.

3. The interpenetrating biopolymers network hydrogel according to claim 2, wherein the ethylenically unsaturated monomer are hydroxyethyl methacrylate (HEMA), and 2-propenamido-2-methyl-1-propanesulfonic acid (AMPS).

4. The interpenetrating biopolymers network hydrogel according to claim 1, wherein the photoinitiator is -ketoglutarate (-KGA), 2,2-diethoxy acetophenone (DEAP), or 2-hydroxy-2-methyl-1-Phenyl-1-acetone (HMPP).

5. The interpenetrating biopolymers network hydrogel according to claim 1, wherein the cross-linking agent is N,N-methylene-bisacrylamide (NMBA), ethylene glycol di(meth)acrylate, 1,4-diacrylic acid piper (PDA)), glutaraldehyde, epichlorohydrin, or a combination thereof.

6. The interpenetrating biopolymers network hydrogel according to claim 1, wherein the cross-linking agent is photo cross-linking agent.

7. The interpenetrating biopolymers network hydrogel according to claim 5, wherein the cross-linking agent is N,N-methylene-bisacrylamide (NMBA).

8. The interpenetrating biopolymers network hydrogel according to claim 1, wherein the pH value is 7.4 to 7.8.

9. The interpenetrating biopolymers network hydrogel according to claim 1, wherein the hydrophilic substance release rate is 40% and above.

10. The interpenetrating biopolymers network hydrogel according to claim 1, wherein the lipophilic substance release rate is 3% and above.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] FIG. 1 shows a schematic diagram of the cross-linked method of present invention.

[0021] FIG. 2 shows a preparation principle of the present invention.

[0022] FIG. 3 shows a schematic diagram of structure of the present invention.

[0023] FIG. 4 shows a release curve of the hydrophilic substance of the present invention.

[0024] FIG. 5 shows a release curve of lipophilic substances of the present invention.

EXAMPLES

Example 1

[0025] FIG. 1 shows the photoinitiator would generate free radicals through UV irradiation and the free radicals would attack monomer or the vinyl group on the cross-linking agent, which made them to generate new free radicals. When new free radicals continuously contacted with monomer, it would initiate a continuous chain extension reaction to form a polymer. Among them, a cross-linked monomer had more than two vinyl groups. When more than two vinyl groups formed free radicals separately and connected with two different polymer chains to form cross-link reaction.

[0026] FIGS. 2 and 3 illustrate that present invention is a preparation method of interpenetrating biopolymers network, comprising dissolving hydroxyethyl methacrylate (HEMA) (1) and 2-propenamido-2-methyl-1-propanesulfonic acid (AMPS) (2) in water according to a specific ratio, adding the photo initiator -ketoglutaric acid (-KGA) (3) and the cross-linking agent (4) N,N-methylenebisacrylamide (NMBA). After mixing them uniformly, injecting with a syringe to prepare in advance in a good glass mold; placing the mold under an ultraviolet light source for photopolymerization. After exposure to UV light for a period of time, the mold is taken out and removed it to obtain the first layer hydrogel. Prepare another mixed solution which comprises HEMA, AMPS, -KGA and NMBA with a specific concentration ratio, soaking the first layer gel (5) made it swell, and after the first layer gel was completely swelled, place it under the ultraviolet light source to make second layer gel (6) photopolymerize. After the reaction was completed, the target interpenetrating network gel could be obtained.

[0027] Table 1 is the implementation process of the present invention that shows the IPN gel at different concentrations, the weight of different monomers and the ratio of cross-linking agent. Production process: dissolving the neutralized AMPS and HEMA in a solvent according to the composition ratio in Table 1, adding the cross-linking agent NMBA and the photo initiator -KGA in sequence. After mixing them uniformly, adjusting the concentration to the target value. Using syringe injected into the glass mold and placed under an ultraviolet light source for photopolymerization. After the reaction was completed, the mold was removed and obtain the first layer gel. Then, the neutralized AMPS, HEMA, NMBA, and -KGA were configured into the second layer gel solution according to the ratio in Table 1. The first layer gel was immersed in the second layer gel solution for swelling, and after it was completely swelled, it was taken out and placed under an ultraviolet light source for the second photopolymerization reaction. After the reaction was completed, the cross-linked hydrogel of the interpenetrating network was obtained.

TABLE-US-00001 TABLE 1 concen- Photo- tration HEMA AMPS NMBA initiator number (M) (mol %) (mol %) (mol %) (mol %) First layer of gel H10A0 3 100 0 3 0.5 H95A5 95 5 3 0.5 H50A50 50 50 3 0.5 H5A95 5 95 3 0.5 H0A100 0 100 3 0.5 Second layer of gel HEMA 0.8 90 10 0.5 0.5

[0028] The Drug Release Test Process of the Present Invention

[0029] Hydrophilic Drug Release

[0030] After the first layer gel was completed, the first layer gel was subsequently immersed in the second layer gel solution for swelling. At this time, the second layer gel solution was mixed with drugs. After it completely swelled, it is taken out and placed under the ultraviolet light source to carry out the second photopolymerization reaction.

[0031] The drug-containing hydrogel was placed in a sustained-release solution for drug release testing and taking the samples from sustained-release solution within a fixed time.

[0032] Taking the samples with fixed time and test releasing concentration. The sampling time is 30 minutes, 60 minutes, 90 minutes, 180 minutes, 8 hours, 24 hours, 48 hours, and 72 hours.

[0033] The subsequent drug concentration was analyzed by high performance liquid chromatography (HPLC). The water-based drug used caffeine for drug release, and the absorption wavelength of caffeine was 272 nm for measurement.

[0034] FIG. 4 shows the caffeine is water-soluble compound. It can be known from the release curve that the release amount of caffeine in water was 40% and above.

[0035] Lipophilic Drug Release

[0036] After the first layer gel was completed, the first layer gel was subsequently immersed in the second layer gel solution for swelling. At this time, the second layer gel solution is mixed with drugs. After it completely swelled, it was taken out and placed under the ultraviolet light source to carry out the second photopolymerization reaction.

[0037] The drug-containing hydrogel was placed in a sustained-release solution for drug release testing and taking the samples from sustained-release solution within a fixed time.

[0038] Taking the samples with fixed time and testing its releasing concentration. The sampling time is 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes, and 180 minutes.

[0039] The subsequent drug concentration was analyzed by high performance liquid chromatography and the lipophilic drug was measured with the absorption wavelength of the lipophilic dye at 210 nm.

[0040] FIG. 5 is release curve shows that the release rate of the lipophilic substance which stored the hydrogel carrier in water was 3% and above.

[0041] The above-mentioned embodiments merely illustrate the effects of the present invention and the technical features of the present invention does not use to limit the protection scope of the present invention. Any change or arrangement can be easily made by a person skilled in the art without departing from the technical principle and spirit of the present invention and these are the scope of the present invention. Therefore, the protection scope of the present invention is as listed in the attached patent scope.