Patent Application
20210130549
The application claims the benefit of TW Patent Application No. 108139285, filed Oct. 30, 2019, which is incorporated herein by reference in its entirety.
The present invention is an interpenetrating biopolymer network hydrogel and its preparation method. It belongs the field of biological medical material.
Biopolymers hydrogel is three-dimensional interpenetrating crosslink network which is composed of nature substance such are protein and polysaccharide that can keep a large amount of water when it is swelling in water. Because biopolymers hydrogel has rich water environment, good biocompatibility and viscoelasticity similar to the structure of biological tissue and that can provide good transmission channels for diffusion of nutrition and biological active ingredient. Its excellent water absorption, water retention and biomimetic properties make biopolymers hydrogel widely be used in the field of biomedical material and tissue engineering. It even can be tissue filling material, drug-controlled release carriers, artificial skin, artificial cartilage, tissue engineering scaffold materials. However, the mechanical strength of hydrogels, especially biopolymers hydrogel, is generally low, which severely restricts its practical application in artificial skin, artificial cartilage and tissue engineering scaffold materials.
The traditional covering structure is composed of natural plant fiber or animal hair materials, such as gauze, cotton pad, wool, various oil gauze, etc., these kind of covering structure are only temporary covering materials, all of them need to be replaced within a period of time. However, these wound patch structures are prone to stick to the wound when they are replaced. Therefore, when the patch structure is torn off, it is possible to tear open new epithelial cells or wounds that have gradually healed. That causes pain and it is difficult for users to bear, and is not conducive to the natural healing of the wound.
Interpenetrating biopolymers network hydrogel is a unique type of network interpenetrating polymer formed by physical or chemical cross-link and entanglement of two or more polymers. Through the form of network interpenetration, two polymers with different functions can form a stable combination, thereby achieving complementary performance between components; its structural characteristics such as interpenetration and bidirectional continuity of the interface make them better in performance or function. Produce special synergies. Compared with block copolymers, the phase morphology of these systems is relatively stable to environmental changes because it is fixed by crosslinking. Therefore, preparing an interpenetrating network is one of the most effective ways to improve the strength of hydrogel.
In order to overcome the low mechanical strength of biopolymers hydrogel, using the structure of interpenetrating network to solve mechanical problems and it also extends the time-releasing of medications. The material of hydrogel in the present invention is 2-Hydroxyethyl methacrylate (HEMA) which is used for contact lenses as main monomer. By adjusting the composition of monomer, the structure of hydrogel can be improved and assess the drug system.
The purpose of the present invention which provides a high mechanism strength biopolymers hydrogel and preparation method. The hydrogel has excellent mechanical properties and biocompatibility. In addition, the present invention applies to development of hydrogel patches and preparation method, which was composed of bidirectional elastic non-woven fabric, hydrogel containing extracts and cover film layer, to solve common allergic phenomenon problem which patches caused.
IPN (interpenetrating polymer network) is a state or structure of cross-linked polymer, which was synthesized from at least one monomer or crosslinked another monomer with cross-linking agent. There is not covalent bond between each other, only when the chemical bond was broken, the monomers of the polymers could be separated.
The present invention was ethylenically unsaturated monomers as materials of the IPN hydrogel. According to different type of monomer, the structure of the IPN hydrogel, time-releasing of medications and water absorption property were improved.
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.
The ethylenically unsaturated monomer used in the IPN hydrogel of the present invention 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.
In the preferred embodiment, the IPN hydrogel used hydroxyethyl methacrylate (HEMA) and 2-propenamido-2-methyl-1-propanesulfonic acid (AMPS) as the main monomers, and added photoinitiator.
The photoinitiator used in the present invention is α-ketoglutarate (α-KGA) or 2,2-diethoxy acetophenone (DEAP), or 2-hydroxy-2-methyl-1-Phenyl-1-acetone (HMPP).
The cross-linking agent which the present invention used is N,N′-methylene-bisacrylamide (NMBA), ethylene glycol di(meth)acrylate, 1,4-diacrylic acid piper (PDA), glutaraldehyde, epichlorohydrin, or a combination thereof.
The present invention is IPN hydrogel, wherein the cross-linking agent is photo cross-linking agent.
The pH value in the present invention is 6.5 to 8.
In the preferred embodiment, the pH value in the present invention is 7.4 to 7.8.
AMPS should be neutralized with NaOH before using it. The prepared pre-polymerization solution should be measured pH value. The pH value should be adjusted with weak acid or weak base before polymerization.
The present invention can be applied to biomedical applications. First the hydrogel itself does not stick to the wound, and has high absorption to lock water and moisturize, maintain a moist and balanced environment, and accelerate wound healing. The hydrogel is translucent that is available to observe the change if the permeate oozes. The hydrogel itself is more comfortable to wear and breathable than the commercially available pressure sensitive adhesive.
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 α-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 α-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.
The Drug Release Test Process of the Present Invention
Hydrophilic Drug Release
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.
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.
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.
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.
Lipophilic Drug Release
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.
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.
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.
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.
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.
| Number | Date | Country | Kind |
|---|---|---|---|
| 108139285 | Oct 2019 | TW | national |
