KR100848712B1 - A photo-crosslinkable thermo-sensitive hydrogel composition and a preparing method thereof - Google Patents

Abstract

A photo-crosslinkable thermo-sensitive hydrogel composition is provided to control sealing and release of drugs by controlling the content of chitosan and ultraviolet irradiation time, so that the composition is useful for delivery of drug. A photo-crosslinkable thermo-sensitive hydrogel composition contains diacrylated pluronic, glycidyl methacrylated chitooligosaccharide, a photo-crosslinking agent, and an active compound selected from peptide, protein, vaccine, antibody, antibody fragment, nucleotide, iRNA(interference RNA), siRNA(small interfering RNA), hormone, cell growth inhibitor, cytotoxic material, anti-inflammatory material, glaucoma-treating agent and urinary incontinence-treating agent, and is prepared by mixing diacrylated pluronic and glycidyl methacrylated chitooligosaccharide with aqueous liquid, adding photo-crosslinking agent and active compound into the mixture and irradiating ultraviolet rays to the mixture. Further, the active compound is one or a plurality of cells alive.

Description

A photo-crosslinkable thermo-sensitive hydrogel composition and a preparing method

1 is a schematic diagram (A) and ¹ H-NMR profile (B) of a production reaction of diacrylated pluronic. Three arrows indicate the acrylated peaks.

Figure 2 is a schematic diagram (A) and ¹ H-NMR profile (B) of the production of glycidyl methacrylated chitosan. Three arrows indicate the acrylated peaks.

Figure 3 is a photograph confirming that the pluronic / chitosan hydrogel of the present invention is a physical gel.

Figure 4 is a photograph of the step of irradiating ultraviolet to the Pluronic / chitosan hydrogel of the present invention.

Figure 5 shows the expansion rate of the photocrosslinked Pluronic / chitosan hydrogel according to various polymer concentrations (18% (A), 20% (B), 22% (C)) of the hydrogel.

6 is a photocrosslinked pluronic according to various photocrosslinking times (10 minutes (A), 15 minutes (B), 20 minutes (C)) when the concentration of the polymer of the hydrogel is 22% (w / v) Decomposition of chitosan hydrogel.

7 is hGH release profile from Pluronic / chitosan hydrogels containing growth hormone (hGH).

The present invention relates to a photocrosslinkable temperature sensitive hydrogel composition and a method for preparing the same, and provides a hydrogel composition including diacrylated pluronic and / or glycidyl methacrylated chitosan.

Hydrogel is a three-dimensional support composed of a polymer that contains a lot of water but is insoluble in water, and is formed by chemical or physical crosslinking. Chemical crosslinks are mainly formed by covalent bonds, and physical crosslinks are formed by hydrophobic bonds, which are physical functions. Hydrogels are suitable for living organisms or can be composed of polymers that exhibit sol-gel transition reactions due to environmental changes, such as temperature or pH, resulting in stimuli-responsive drug delivery, It has been applied to fields such as medicine, beauty and pharmaceuticals. One recent trend of research and development in hydrogels is the formation of in situ hydrogels by photo-polymerization or phase transition. In situ hydrogels increase the potential for hydrogels to be applied in macromolecular drug delivery, tissue barriers and tissue engineering.

The macromolecules used to make hydrogels include agarose, hyaluronic acid, chitosan, and gelatin, which are natural polymers. However, some aqueous solutions of cellulose derivatives exhibit the opposite thermogelation. Methyl cellulose and hydroxypropyl cellulose are typical examples. The combination of chitosan and glycerol phosphate disodium salt also shows the opposite thermogelation. In addition to natural polymers, research has been focused on multi-block copolymers showing sol-gel transitions, including N- isopropylacrylamide (NiPAAM) copolymer, Pluronic ( poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) (Poloxamer, Pluronic®)) and polyethylene glycol / polylactic acid-glycolic acid block copolymers (poly (ethylene glycol) / poly (D, L- lactic acid-co-glycolic acid) block copolymer).

Using a temperature-sensitive polymer as described above to make a gel, it can be used as a drug carrier by adding a drug to it or by mixing later. In order to maximize the effect of the drug locally or at the desired location, a method of enclosing the drug in a carrier such as nano or micro size carriers and hydrogels has been reported to induce the release of the drug at the required site. There remains a problem for effective control.

In order to solve the above problems, in the present invention, the acrylic group is dissolved in the hydroxyl group of chitooligosaccharide and the terminal hydroxyl group of the pluronic F127 so as to enable photocrosslinking. The added polymer is synthesized and a temperature sensitive gel made of these polymers is provided. In addition, gels containing these and photocrosslinkers were prepared to find a sol-gel transition temperature in the physical gel state, and a photopolymerization reaction was performed by irradiating ultraviolet (UV) light to prepare a photocrosslinkable hydrogel, and its swelling, decomposition, and drug release properties. By analyzing the Suggest ways to control effectively.

In the present invention, an acrylic group was added to chitosan and pluronic, which are biocompatible polymers, so that a polymerization reaction may occur by photocrosslinking. That is, glycidyl methacrylate is added to the hydroxyl group of chitosan to synthesize glycidyl methacrylated chito-oligosaccharide, and acrylic acid is added to the hydroxyl groups at both ends of Pluronic F127. Diacrylated pluronics were synthesized. By adjusting the ratio of these polymers, a gel containing a photocrosslinking agent was prepared to find a sol-gel transition temperature in the physical gel state, and irradiated with UV light to cause a polymerization reaction to prepare a photocrosslinkable hydrogel in a chemical gel state. The drug release characteristics were analyzed.

Pluronic (PEO-PPO-PEO) is a biocompatible polymer that is degraded under physiological conditions and is safe in humans. In addition, there is a hydrophobic block (PPO) that has a low critical solution temperature (LCST) characteristic, which allows self-assembly at high temperatures and is temperature sensitive. Biocompatible chitooligosaccharides having a double bond were added to the pluronic and irradiated with ultraviolet light to prepare a photocrosslinkable hydrogel.

The inventors of the present invention have found a low critical solution temperature (LCST) using a physical gel that can change from a low temperature to a sol state. As a result, a pluronic hydrogel containing chitosan is higher than a hydrogel prepared solely with pluronics. It was confirmed that it gelled at. Therefore, Pluronic hydrogel containing chitosan When injectable gels are injected into the body via injection, the possibility of gelling and clogging the needle is reduced compared to hydrogels made only of pluronic gels that gel at low temperatures. However, since the gelation temperature is still lower than the temperature in vivo, the hydrogel of the present invention injected into the body can form a physical gel by the temperature in vivo.

The inventors made a photocrosslinkable gel with the hydrogel composition of the present invention and measured the degree of swelling and degradation. In the photocrosslinkable hydrogel, the degradation decreased as the chitosan content increased from 0 to 15%. Multiple acrylated chitosans enter between the crosslinked pluronic polymers and crosslink to increase the interconnection of the pluronic / chitosan hydrogels. Therefore, the higher the content of chitosan, the higher the degree of interconnection, the lower the degree of degradation compared to the lower content of chitosan.

After adding a human growth hormone (hGH) to prepare a hydrogel, the release pattern of the growth hormone was measured. Chitosan content and UV irradiation time influenced the protein release pattern in hydrogel. The reason is that the hydrogel contains a positively charged chitosan and a negatively charged protein, thus suppressing the release of the drug and exhibiting sustained release behavior.

Based on this, the present invention provides a hydrogel composition comprising diacrylated pluronic and glycidyl methacrylated chitooligosaccharide. The hydrogel of the present invention is prepared by a method comprising mixing diacrylated pluronic and glycidyl methacrylated chitooligosaccharides with an aqueous liquid. The hydrogel manufacturing method may further include adding a photocrosslinker, irradiating ultraviolet rays and / or adding an active compound. The hydrogel manufacturing method of the present invention also comprises the steps of preparing diacrylated fluoronics by reacting with pluronic and acryloyl chloride and glycidyl meta by reacting chitooligosaccharide and glycidyl methacrylate (methacrylate). It may further comprise the step of preparing a crystallized chitooligosaccharide.

The hydrogel composition may further include a crosslinking agent. As a crosslinking agent, for example, an optical crosslinking agent such as Irgacure 2959 may be used, but is not limited thereto. The ratio of glycidyl methacrylated chitooligosaccharide and diacrylated pluronic can be adjusted according to the characteristics of the hydrogel to be prepared. For example, when it is desirable to gel at higher temperatures or to reduce degradation, the content of glycidyl methacrylated chitooligosaccharides is increased. In addition, the total composition ratio of the polymer forming the hydrogel can also be adjusted according to the characteristics of the hydrogel desired.

Hydrogel of the present invention is a temperature-reactive, sol-gel phase transition phenomenon according to the temperature, it can be used to deliver the drug to the desired place when desired. In addition, the hydrogel of the present invention is chemically cross-linked through ultraviolet irradiation, and the swelling, decomposition and drug release patterns of the hydrogel are affected by the crosslinking density, and the crosslinking density depends on the amount of acrylic groups, light irradiation time, etc. It is possible to adjust this according to the characteristics.

As an aqueous liquid used to prepare the photocrosslinked hydrogel of the present invention, water or an aqueous buffer solution is preferable. However, any solvent can be used which has a good effect on the photopolymerization process or on the properties of the hydrogel. Suitable solvents include, for example, acetone, methyl ethyl ketone, methanol, ethanol, propanol, butanol, ethyl acetate, butyl acetate, methylene chloride, water and mixtures thereof.

Preferably, the hydrogel composition of the present invention further comprises an active compound. The active compound may be any chemical, biological material or mixture of these materials useful for diagnosing, preventing or treating a disease, signs and other symptoms of the body or acting on the body function. In addition, the active compound may be a compound related to cosmetics, skin care, skin care. The hydrogel composition comprises at least one, optionally two or more active compounds.

Preferred active compounds include drugs used in chronic or long-term therapy, for example hormones, growth factors, hormonal antagonists, antipsychotics, antidepressants, cardiovascular agents and the like. In addition, the active compound of the present invention may be a peptide or protein, for example, erythropoietin, interferon, insulin, antibody, antibody fragment, blood factor, colony stimulating factor, growth hormone, interleukin, growth factor, LHRH analog , Vaccines and the like. In addition, polysaccharides and polynucleotides, DNA, RNA, iRNA, siRNA, antibiotics and living cells. Other small molecules, cytostatic agents, cytotoxic substances and central nervous system agonists may be included. In addition, the hydrogel of the present invention may comprise one or a plurality of living cells.

The active compound may be present in the form of a hydrogel, or be incorporated in the form of a colloidal carrier loaded with a drug, for example, nanoparticles, nanocapsules, liposomes, lipoplexes, lipid complexes, solid lipid nanoparticles or drug conjugates. Can be.

The hydrogel composition of the present invention may be designed for topical, oral, rectal, vaginal, ocular or pulmonary administration, preferably parenteral or pulmonary administration. Parenteral administration in the present invention encompasses all permeable routes of administration such as subdermal, transdermal, subcutaneous, intramuscular, topical, intratumoral, intraperitoneal, intracellular, wound and within the scope of the present invention and also intravenously , Intravenous and the like. Pulmonary administration includes oral or nasal inhalation by nebulizer, powder inhaler.

The hydrogel composition of the present invention is formulated in a form suitable for parenteral administration. Formulation methods follow the methods described in the Pharmacopoeia. The hydrogel composition incorporates additional excipients such as stabilizers, bulking agents, matrix formers, lyophilization aids, antioxidants, chelating agents, preservatives, solvents, cosolvents, surfactants, osmotic substances, pH adjusting acids or alkali excipients, and the like. Can be.

The active compound included in the hydrogel composition of the present invention is often unstable under aqueous conditions. Therefore, in order to increase storage stability, a kit for preparing a hydrogel composition which can be reconstituted with an appropriate aqueous carrier immediately before administration can be prepared. Preferably, the kit is provided to an end user, such as a doctor, nurse, pharmacist, or patient, and contains all the ingredients necessary to prepare the hydrogel composition. In one example the kit comprises an active compound, a diacrylated pluronic, glycidyl methacrylated chitooligosaccharide and an aqueous liquid for reconstitution of the gel composition. And may include excipients such as stabilizers, bulking agents, matrix formers, lyophilization aids, antioxidants, chelating agents, preservatives, solvents, cosolvents, surfactants, osmotic materials, pH adjusting acids or alkaline excipients, and the like. have. Aqueous liquids mainly contain water. Or further excipients such as one or more osmotic substances (eg, NaCl, sugars or alcohols) or surfactants or excipients for adjusting pH.

The hydrogel composition of the present invention can be used in pharmaceuticals and cosmetics, and can be used as a support for tissue engineering. The hydrogel composition of the present invention may slowly release the active compound for a predetermined time period, for example for several days, weeks or months. Slow release in the present invention includes all types of modified release modalities such as controlled release, sustained release, prolonged release, pulsed release and the like.

Hereinafter, embodiments of the present invention will be described in more detail a part of the present invention, but the scope of the present invention is not limited thereto.

Example

Reagents and Samples

Pluronic F-127 ((PEG) ₉₉ (PEO) ₆₉ (PEG) ₉₉ ) was obtained from BASF (Germany) and chito-oligosaccharide (COS) was purchased from KITTO LIFE (Korea). Triethylamine was purchased from Sigma, and glycidyl methacrylate was purchased from Junsei Chemical (Japan). Acryloyl chloride was purchased from Aldrich. Irgacure 2959, a photocrosslink, was received by Ciba Specialty Chemicals (Tarrytown, NY). Growth hormone (hGH) was purchased from Sigma.

Example 1 Synthesis of Diacrylated Pluronic F127

40 g of Pluronic F127 and 1 g of triethylamine, which were dried overnight in vacuo, were dissolved in 50 ml of dichloromethane. When all dissolved, 0.56 g of acryloyl chloride was added and purged with N ₂ gas, followed by stirring at 4 ° C. for 12 hours, followed by stirring at 24 ° C. for 12 hours. After the reaction was completed, the precipitate was precipitated with a sufficient amount of diethyl ether, which had been cooled in a freezer, and filtered. The precipitate was dried in the hood for a period of time and then completely dried in vacuo. The synthesized polymer was dissolved in CDCl ₃ and measured by 400MHz ¹ H NMR spectrum to determine the degree of acrylation. The value is 33.6%.

Example 2 Synthesis of Glycidyl Methacrylated Chitooligosaccharide

3 g of chitooligosaccharides were dissolved in 30 ml of distilled water, and then 0.826 ml of glycidyl methacrylic acid was slowly added. Purged with nitrogen gas and stirred at 40 ° C. for 12 hours. The composite was precipitated with acetone cooled in the freezer, filtered and dried. Glycidyl methacrylic acid was bound to the hydroxyl group of the repeating unit of chitosan to form glycidyl methacrylated chitosan. As a result of 400MHz ¹ H NMR measurement, the degree of substitution was 16.0%.

Example 3 Preparation of Pluronic / Chitosan Hydrogel

A hydrogel containing 20% (w / v) of polymer was prepared as follows. 100 mg, 95 mg, 90 mg, and 85 mg of di-acrylated Pluronic F127 were mixed with 0 mg, 5 mg, 10 mg, 15 mg, and tertiary distilled water to 500 μl of methacrylated chitooligosaccharide, respectively. Alternatively, Irgacure2959, which is 0.3% (w / v) of the total volume, was added to the composition to obtain a total of 500 μl.Methacrylate chitooligosaccharide and Irgacure may be first dissolved in distilled water. The mixture was mixed well on a twist shaker, and the sol state sample was taken out of the refrigerator and placed in a water bath at 37 ° C. for about 10 minutes to make a physical gel, and turned upside down to confirm that the gel was formed (FIG. 3).

Pluronic / chitosan hydrogel containing 18% (w / v) and 22% (w / v) of the polymer by varying the amount of diacrylated pluronic and methacrylated chitooligosaccharides. Was prepared.

Example 4 Preparation of Photocrosslinked Pluronic / Chitosan Hydrogels

A total 500 μl solution was prepared with the amount of diacrylated pluronic, methacrylated chitooligosaccharides used in Example 3, and Irgacure2959 and tertiary distilled water at 0.3% (w / v) of total volume. The prepared solution was put in a refrigerator and mixed well on a twist shaker. The sol sample was taken out of the refrigerator and placed in a water bath at 37 ° C. for 10 minutes to form a physical gel, and turned upside down to confirm that the gel had formed. Next, UV was irradiated for 10 minutes, 15 minutes, and 20 minutes at 1.5 cm from the gel to make a chemical gel (Fig. 4). It was confirmed that the chemical gel did not become sol when left in the refrigerator for more than 3 hours.

Example 5 Sol-Gel Phase Transition Temperature Measurement of Pluronic / Chitosan Hydrogel

Incubate a 2 ml tube containing 0.5 ml of a sol mixture containing 18, 20, and 22% (w / v) of the polymer in a hydrogel for 15 minutes at a temperature of 5 ° C to 80 ° C in 2 ° C increments. After the tube was turned upside down, the temperature at which the tube became a gel state and the temperature at which the tube became a sol state was again found. The ratio of glycidyl methacrylated chitooligosaccharide and di-acrylated pluronic (di-acrylated Pluronic F127) was set to 0/100, 5/95, 10/90, and 15/85 (w / w). In hydrogels that do not contain chitosan, the sol-gel change temperature drops slightly from 25 ° C to 22 ° C as the polymer concentration increases. The low critical solution temperature (LCST) increased little by little as the content of chitosan increased in the pluronic / chitosan hydrogel. In the hydrogel composition of the present invention, the composition having a high LCST can be utilized as a preparation to slowly release the drug by gelling locally when the photocrosslinkable hydrogel is injected with the drug in a sol state and irradiated with ultraviolet rays.

Phase transition temperature of pluronic / chitosan hydrogel when the total concentration of polymer is 18% (w / v) (A), 20% (w / v) ( B ), 22% (w / v) (C) Chitosan weight% ¹  0  5  10  15  A  Sol-> gel 25 ^o C 27 ^o C 29 ^o C N / D ²  Gel-> sol 56 ^o C 54 ^o C 49 ^o C N / D ²  B  Sol-> gel 22 ^o C 22 ^o C 24 ^o C 26 ^o C  Gel-> sol 68 ^o C 62 ^o C 58 ^o C 54 ^o C  C  Sol-> gel 20 ^o C 20 ^o C 21 ^o C 22 ^o C  Gel-> sol 78 ^o C 74 ^o C 72 ^o C 71 ^o C

1 Weight of Chitosan in Pluronic and Chitosan Mixtures

2 not determined

Example 6 Photo-crosslinking of Pluronic / Chitosan Hydrogels

The total polymer dry weight ratio of the hydrogel is 18, 20, 22% (w / v) (i.e., 1 g of water is used to mix 180g, 200g, 220g of the polymer), among which glycidyl metak The ratio of the related chitooligosaccharides and di-acrylated pluronic F127 is 0/100, 5/95, 10/90, 15/85 (w / w), and each is mixed into 2 ml tubes. The total volume was made to 500 μl. Irgacure 2959 was added as a photo-initiator to 0.3% of the total volume. The mixture was mixed at 4 ° C. It was left at 37 ° C. for 10 minutes to make a physical gel. Ultraviolet (UV) rays were irradiated for 10 minutes, 15 minutes, and 20 minutes at a distance of 1.5 cm to produce a chemical gel.

Example 7 Swelling Properties of Pluronic / Chitosan Hydrogels

Pluronic / chitosan hydrogels prepared in Example 6 were chemically gelled with ultraviolet rays and then lyophilized to determine the weight of the gel itself (W _d ). In each tube containing lyophilized gel 1.5ml each of 10mM phosphate buffer solution at pH 7.4 was added and incubated for 12 hours in a shaking incubator at 37 ° C. After 12 hours, the weight of the swollen hydrogel (swollen hydrogel) was measured (W _s ), and the degree of swelling was calculated using the formula (%) = [(W _s -W _d ) / W _d ] X 100.

5 is a result of measuring the swelling ratio while varying the UV irradiation time and the amount of glycidyl methacrylated chitooligosaccharide of the hydrogel. Irrespective of the chitosan oligosaccharide content of the pluronic / chitosan hydrogel, the swelling ratio decreased little by little as the UV irradiation time was increased from 10 minutes to 20 minutes. This is thought to be the result of the increased molecular network between glycidyl methacrylated chitooligosaccharide (Glycidyl methacrylated COS) and diacrylated pluronic by UV irradiation. Increasing the UV irradiation time increases the crosslinking density of the hydrogel, so you can reduce the UV irradiation time to absorb more water. The hydrogel containing 22% chitosan showed the most significant effect of UV irradiation time than the hydrogel containing 18% and 20%. The chitooligosaccharide content of the hydrogel had an effect on the swelling ratio of the pluronic / chitosan hydrogel. The swelling ratio gradually decreases when the UV irradiation time is the same and the ratio of chitosan is increased, because the amount of chitosan added is increased so that the rigidity of the Pluronic hydrogel, which is tightly linked and networked between molecules, is reduced. That is, LCST is affected by the chitosan content ratio of the pluronic / chitosan hydrogel.

Example 8 Degradation of Photocrosslinked Pluronic / Chitosan Hydrogel

Pluronic / chitosan hydrogel of the present invention was irradiated with ultraviolet rays to form a chemical gel and then lyophilized to determine the weight of the gel itself. Each tube was dried with 1.5 ml of dried gel and phosphate buffer solution, incubated in a 37 ° C shaking incubator for 2, 4, 7, 14, and 21 days, and then lyophilized to determine the weight of the dried gel and degraded. The degree was calculated.

Increasing UV irradiation time suppressed the degree of degradation, and the higher the degree of crosslinking, the lower the degree of degradation. When the irradiation time of ultraviolet rays was the same and the chitosan content of the hydrogel was changed, the effect on the degree of decomposition was faster in the hydrogel containing no chitosan than in other hydrogels containing chitosan. Irrespective of the UV irradiation time, the decomposition rate decreased as the chitosan content in the hydrogel increased from 5% to 15% (Fig. 6).

Multiple acrylated chitosans enter between the crosslinked pluronic polymers and crosslink to increase the interconnection of the pluronic / chitosan hydrogels. Therefore, the higher the content of chitosan, the higher the degree of interconnection, the lower the degree of degradation compared to the lower content of chitosan. Hydrogels containing 15% chitosan are gelled at higher temperatures than those with other% chitosan, so Pluronic / Chitosan hydrogels do not undergo a phase transition from sol to gel during in vivo injection through a syringe. Needle is not clogged. In addition, the Pluronic / chitosan hydrogel, which is maintained in the physical gel state after being injected into the body in a sol state, is photocrosslinked with ultraviolet rays to form a chemical gel, thereby further improving the mechanical strength of the gel, thereby injecting the injected drug. Maintain high concentrations locally only at the desired area.

Example 9 Protein Release Profiles from Pluronic / Chitosan Hydrogels

22% (w / v) Pluronic / chitosan solution was incubated for 10 minutes incubated at 37 ℃ the amount of growth hormone (hGH) released was measured by the BSA assay kit (Fig. 7).

According to the chitosan content of the hydrogel and UV irradiation time, different hGH emission characteristics were shown. The initial degree of diffusion was dependent on the chitosan content of the Pluronic / Chitosan hydrogel, and the hydrogel containing 15% chitosan showed the most sustained release pattern compared to other hydrogels. In the next step, the degree of protein release can be controlled by chitosan content as well as UV irradiation time. Increasing the irradiation time was found to delay the release of protein. Positive charge Inhibition of protein release in hydrogels consisting of prominent chitosan and negatively charged hGH can be attributed to ionic bonds occurring between substances with opposite charges. There is applicability to hydrogels that can control the release of negatively charged proteins of various growth hormones containing physiological pH.

Pluronic hydrogel containing chitosan of the present invention has a higher gelation temperature compared to hydrogel consisting solely of Pluronic, so that the needle clogging during in vivo injection using a syringe is reduced. And the photocrosslinked hydrogel decomposes slowly when it contains chitosan. The inclusion of chitosan also affects the release of negatively charged proteins with UV irradiation time. Therefore, by controlling the content of the chitosan and the ultraviolet irradiation time of the pluronic / chitosan hydrogel of the present invention it is possible to implement a desired drug release pattern.

In addition, when the photo-crosslinked hydrogel of the present invention is injected with a drug in a sol state and exposed to ultraviolet rays, the photocrosslinked hydrogel may be gelled locally to gradually release the drug. Therefore, since it is a sol state in the body and gelled in the body, it can be used as an agent for the local chemotherapy of solid cancer. In addition, it can be applied to anti-inflammatory and glaucoma treatment, etc., to compensate for the shortcomings such as the rapid diffusion of drugs commonly occurring during eyedrops and to facilitate the patient's convenience.

The pluronic / chitosan hydrogel of the present invention also exists in a sol state in vitro when a periurethral filler injection method, which is one of the treatments of stress incontinence in women, causes a sol in vitro to change to a gel state when injected into the urethra. It is in a state of being non-sticky and can be easily stored and injected. In addition, the amine group of chitosan inside the gel can be used for gene therapy because it can self-assemble with DNA.

Claims (17)

Hydrogel composition comprising diacrylated pluronic and glycidyl methacrylated chitooligosaccharide. The hydrogel composition of claim 1, further comprising a photocrosslinking agent. The hydrogel composition of claim 1, wherein the hydrogel is chemically or physically crosslinked. The hydrogel composition of claim 1, wherein the hydrogel is temperature reactive. The hydrogel composition of claim 1, further comprising an active compound. 6. The hydrogel composition of claim 5, wherein the active compound is incorporated into a hydrogel. The method of claim 5, wherein the active compound is a peptide, protein, vaccine, antibody, antibody fragment, nucleotide, iRNA, siRNA, hormones, cell proliferation inhibitors, cytotoxic substances and substances that act on the central nervous system, anti-inflammatory agents, glaucoma agents and urinary incontinence Hydrogel composition, characterized in that selected from the group consisting of therapeutic agents. The hydrogel composition of claim 5, wherein the active compound is one or a plurality of living cells. The hydrogel composition of claim 1, wherein the hydrogel composition is for parenteral administration. The kit for preparing a hydrogel composition according to any one of claims 1 to 9, comprising an active compound, a diacrylated pluronic, glycidyl methacrylated chitooligosaccharide, and an aqueous liquid for reconstitution of a gel composition. A pharmaceutical comprising the hydrogel composition according to any one of claims 1 to 9. A support for tissue engineering, comprising the hydrogel composition according to any one of claims 1 to 9. A cosmetic comprising the hydrogel composition according to any one of claims 1 to 9. A method for preparing a hydrogel comprising mixing a diacrylated pluronic and glycidyl methacrylated chitooligosaccharide with an aqueous liquid. The method of claim 14, further comprising adding a photocrosslinker and irradiating light. The method for producing a hydrogel according to claim 15, wherein the light to be irradiated is ultraviolet light. 15. The method of claim 14, further comprising the step of adding an active compound.

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