CN115671371B - Hemostatic hydrogel and preparation method and application thereof - Google Patents
Hemostatic hydrogel and preparation method and application thereof Download PDFInfo
- Publication number
- CN115671371B CN115671371B CN202110843773.6A CN202110843773A CN115671371B CN 115671371 B CN115671371 B CN 115671371B CN 202110843773 A CN202110843773 A CN 202110843773A CN 115671371 B CN115671371 B CN 115671371B
- Authority
- CN
- China
- Prior art keywords
- hydrogel
- hemostatic
- methacrylamide
- compound
- photoinitiator
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000017 hydrogel Substances 0.000 title claims abstract description 87
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 81
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- -1 aldehyde compound Chemical class 0.000 claims abstract description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000000499 gel Substances 0.000 claims abstract description 20
- 230000009471 action Effects 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 238000004132 cross linking Methods 0.000 claims description 14
- 229920000858 Cyclodextrin Polymers 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 claims description 7
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 6
- 229920001661 Chitosan Polymers 0.000 claims description 6
- 108010010803 Gelatin Proteins 0.000 claims description 6
- 239000008273 gelatin Substances 0.000 claims description 6
- 229920000159 gelatin Polymers 0.000 claims description 6
- 235000019322 gelatine Nutrition 0.000 claims description 6
- 235000011852 gelatine desserts Nutrition 0.000 claims description 6
- 229920002674 hyaluronan Polymers 0.000 claims description 6
- 229960003160 hyaluronic acid Drugs 0.000 claims description 6
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims description 6
- 239000001913 cellulose Substances 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- 229940117916 cinnamic aldehyde Drugs 0.000 claims description 3
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims description 3
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims description 3
- 235000012141 vanillin Nutrition 0.000 claims description 3
- GJKGAPPUXSSCFI-UHFFFAOYSA-N 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone Chemical group CC(C)(O)C(=O)C1=CC=C(OCCO)C=C1 GJKGAPPUXSSCFI-UHFFFAOYSA-N 0.000 claims 1
- RFDVZWOFSNTAJH-UHFFFAOYSA-N CC(C(=O)N)=C.[Na] Chemical compound CC(C(=O)N)=C.[Na] RFDVZWOFSNTAJH-UHFFFAOYSA-N 0.000 claims 1
- 229920001744 Polyaldehyde Polymers 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 210000000056 organ Anatomy 0.000 abstract description 14
- 239000007787 solid Substances 0.000 abstract description 13
- 230000000740 bleeding effect Effects 0.000 abstract description 10
- 206010052428 Wound Diseases 0.000 abstract description 9
- 208000027418 Wounds and injury Diseases 0.000 abstract description 9
- 239000000463 material Substances 0.000 abstract description 8
- 208000031737 Tissue Adhesions Diseases 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 3
- 239000002861 polymer material Substances 0.000 abstract description 2
- 239000008280 blood Substances 0.000 abstract 2
- 210000004369 blood Anatomy 0.000 abstract 2
- 239000000243 solution Substances 0.000 description 39
- 241000700159 Rattus Species 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 8
- 230000023597 hemostasis Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- 210000002216 heart Anatomy 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 5
- 230000001070 adhesive effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- 229920002101 Chitin Polymers 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 229910021389 graphene Inorganic materials 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000004298 light response Effects 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000003106 tissue adhesive Substances 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- ATMNSERBBXSKKP-UHFFFAOYSA-N 1H-pyrimidin-2-one urea Chemical compound N1C(N=CC=C1)=O.NC(=O)N ATMNSERBBXSKKP-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920003020 cross-linked polyethylene Polymers 0.000 description 1
- 239000004703 cross-linked polyethylene Substances 0.000 description 1
- LKFHUFAEFBRVQX-UHFFFAOYSA-N decanedioic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.OC(=O)CCCCCCCCC(O)=O LKFHUFAEFBRVQX-UHFFFAOYSA-N 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Chemical compound CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a hemostatic hydrogel and a preparation method and application thereof, and belongs to the technical field of high polymer materials. The hydrogel is prepared from the following raw materials in percentage by mass: 1 to 20 percent of aldehyde compound, 10 to 30 percent of methacrylamide compound, 0.1 to 2 percent of photoinitiator and the balance of water. The double-network hemostatic hydrogel provided by the invention has viscoelasticity and fluidity, can be injected into tissues at a bleeding part in vitro, forms solid gel under the action of a photoinitiator when reaching the tissues, can rapidly stop blood, has firm tissue adhesion, can rapidly stop blood and heal multiple organ wounds after operation, and can be widely applied to preparation of rapid hemostatic materials.
Description
Technical Field
The invention belongs to the technical field of high polymer materials, and particularly relates to a hemostatic hydrogel and a preparation method and application thereof.
Background
The Gong's teaching at North sea university for the first time suggests a dual network hydrogel consisting of two distinct polymer networks: the hydrogel is composed of two interpenetrating crosslinked networks, wherein the first network is formed by ultraviolet irradiation under light response, and the second network is formed by self Schiff base reaction. The injectable double-network hydrogel means that the hydrogel forming system is respectively in two syringes before gel forming and can flow, and after the hydrogel forming system is directly injected to a target site, gels with different shapes are automatically formed to adapt to wounds. Therefore, the injectable double-network hydrogel is widely focused and has wide application in tissue engineering of heart, liver and skin. Because of its excellent mechanical properties and biocompatibility, the double-network injectable hydrogel is one of the most promising candidates for hemostatic adhesive materials, and development of a polymeric material with hemostatic function is highly demanded.
In recent years, many methods for preparing double-network hydrogels have been reported at home and abroad to improve the adhesion of biological surfaces. The Dominique team uses covalently crosslinked polyethylene glycol dimethacrylate and ionically crosslinked alginate as a matrix, which is reinforced with nanofibrillated cellulose (DOI: 10.1021/acsami.8b 10735). The rigid fiber network acts as a dissipative material to maximize the protection of the contact points. The hydrogel can obtain higher adhesive property without modifying the surface of the tissue. Team Guo Baolin developed a physical DN self-healing hydrogel that was injectable under physiological conditions for the treatment of multi-drug resistant bacterial infections and full-thickness skin incision/defect repair (DOI: 10.1002/adfm.201910748). The hydrogel adhesive consists of catechol-Fe < 3+ > coordination crosslinked poly (glycerol sebacate) -co (ethylene glycol) -g-catechol and quadruple hydrogen bond crosslinked urea pyrimidone modified gelatin. However, the rapid hemostatic performance and biocompatibility of the hydrogels are still further improved.
Disclosure of Invention
In order to solve the technical problems, the invention provides a hemostatic gel which can form hydrogel in situ under the action of a photoinitiator and has rapid hemostatic performance and good biocompatibility.
The invention provides a hemostatic hydrogel which is prepared from the following raw materials in percentage by mass:
1 to 20 percent of aldehyde compound, 10 to 30 percent of methacrylamide compound, 0.1 to 2 percent of photoinitiator and the balance of water.
Further, the aldehyde-based compound includes at least one of anisaldehyde, polyallylglycol (CHO-PEG-CHO), cinnamaldehyde, vanillin, and cyclodextrin aldehyde.
Further, the aldehyde-based compound is cyclodextrin aldehyde.
Further, the methacrylamide compound comprises at least one of methacrylated gelatin, amino graphene, methacrylated hyaluronic acid, methacrylated sodium alginate, methacrylated glucose, methacrylated chitosan, methacrylated cellulose, methacrylated carboxymethyl chitosan, amino gelatin, amino polysaccharide or amino chitin.
Further, the methacrylamide compound is methacryloylated hyaluronic acid.
Further, the photoinitiator is 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionacetone.
The invention also provides a preparation method of the hemostatic hydrogel, which comprises the following steps:
Dissolving an aldehyde compound in water to obtain a solution S1;
Dissolving a methacrylamide compound and a photoinitiator in water to obtain a solution S2;
And mixing the solution S1 and the solution S2, and performing crosslinking reaction under the action of ultraviolet irradiation to obtain the hemostatic hydrogel.
Further, the temperature of the crosslinking reaction is 10-40 DEG C
The invention also provides the application of the hemostatic hydrogel in a solid organ.
Further, the solid organs include heart, liver, spleen, lung, kidney.
The invention has the following advantages:
The hemostatic hydrogel is a dual-network hemostatic hydrogel, and is prepared by adopting a dual-component system with light response, and comprises an aldehyde compound and a methacrylamide compound, the obtained hemostatic hydrogel has viscoelasticity and fluidity, can be injected into tissue at a bleeding part in vitro to irregular wound tissue to form solid gel, has a rapid hemostatic effect, has firm tissue adhesion, can be locally reserved in a body for one month, can be well healed at the bleeding part after operation, has good biocompatibility and no inflammatory reaction, and overcomes the defects of large dosage and need of replacement at different parts of the conventional common hydrogel product.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
In the drawings:
fig. 1 shows the practical use of the hemostatic hydrogel of the present invention in a rat heart.
Figure 2 shows the practical use of the hemostatic hydrogel of the invention in rat liver.
Figure 3 shows the practical use of the hemostatic hydrogel of the invention in the spleen of rats.
Fig. 4 shows the practical use of the hemostatic hydrogel of the invention in rat lung.
Fig. 5 shows the practical use of the hemostatic hydrogel of the present invention in rat kidneys.
Figure 6 shows the use of the hemostatic hydrogel of the invention after one month recovery of the rat liver.
Fig. 7 shows the practical use of a commercial hemostatic hydrogel in rat liver.
FIG. 8 shows the cellular activity of the hemostatic hydrogels of the invention in HUVEC and L929.
Detailed Description
The technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. Embodiments of the invention and features of the embodiments may be combined with each other without conflict.
An embodiment of the invention provides a hemostatic hydrogel, which is prepared from the following raw materials in percentage by mass:
1 to 20 percent of aldehyde compound, 10 to 30 percent of methacrylamide compound, 0.1 to 2 percent of photoinitiator and the balance of water.
The double-network hemostatic hydrogel provided by the embodiment of the invention comprises an aldehyde group compound, an amino-containing methacrylamide compound and an amide-containing methacrylamide compound, and has a multi-response component system, wherein the aldehyde group compound and the amino-containing compound in the methacrylamide compound react to form a first crosslinked network, and the methacrylamide compound itself generates a photo-crosslinking reaction to form a second crosslinked network. The double reactions occur simultaneously, which can rapidly realize hemostasis and enhance adhesion.
The hemostatic hydrogel obtained by the embodiment of the invention has viscoelasticity and fluidity, can be injected into tissues at a bleeding part in vitro, forms solid gel under the action of a photoinitiator when reaching the tissues, has firm tissue adhesion, and can realize rapid hemostasis. In addition, the hemostatic hydrogel disclosed by the invention has good biocompatibility and no inflammatory reaction, and overcomes the defects that the conventional common hydrogel product has large dosage and different parts need to be replaced.
Further, the aldehyde-based compound includes at least one of anisaldehyde, polyallylglycol (CHO-PEG-CHO), cinnamaldehyde, vanillin, and cyclodextrin aldehyde.
Further, the aldehyde-based compound is cyclodextrin aldehyde.
Further, the methacrylamide compound comprises at least one of methacrylated gelatin, amino graphene, methacrylated hyaluronic acid, methacrylated sodium alginate, methacrylated glucose, methacrylated chitosan, methacrylated cellulose, methacrylated carboxymethyl chitosan, amino gelatin, amino polysaccharide or amino chitin.
Further, the methacrylamide compound is methacrylamide hyaluronic acid.
Further, the photoinitiator is 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionacetone.
The invention also provides a preparation method of the hemostatic hydrogel, which comprises the following steps:
Dissolving an aldehyde compound in water to obtain a solution S1;
Dissolving a methacrylamide compound and a photoinitiator in water to obtain a solution S2;
And mixing the solution S1 and the solution S2, and performing crosslinking reaction under the action of ultraviolet irradiation to obtain the hemostatic hydrogel.
Further, the temperature of the crosslinking reaction is 10 to 40 ℃. In the preparation method of the bleeding stopping hydrogel, the solution S1 containing the aldehyde group compound and the solution S2 containing the methacrylamide compound and the photoinitiator are mixed at normal temperature, and the bleeding stopping hydrogel can be obtained through crosslinking reaction under the action of ultraviolet irradiation, the reaction condition is mild, and the preparation method is simple.
The invention also provides application of any hemostatic hydrogel in a solid organ.
Further, the solid organs include heart, liver, spleen, lung, kidney, etc.
Further, in order to inhibit the growth and reproduction of microorganisms and bacteria and promote the healing of wounds, the hemostatic hydrogel preferably further comprises a preservative and a bacteriostatic agent. Wherein, the antibacterial agent and the preservative can be commercial preservatives.
Further, the water may be deionized water or physiological saline.
The hemostatic hydrogel disclosed by the invention has excellent hemostatic performance and firm tissue adhesion, can be widely used for rapidly stopping bleeding in a wet environment, and is suitable for various solid organs.
The invention also provides a material which can quickly stop bleeding and is suitable for various solid organs, and the material comprises the hemostatic hydrogel.
In order to better apply to the hemostasis of surgery, the embodiment of the invention also provides a system for preparing the rapid hemostasis, which comprises a syringe A and a syringe B, wherein the syringe A comprises a mixed solution of a component A (aldehyde-based compound) and a photoinitiator, and the syringe B comprises a component B (methacrylamide compound).
When the rapid hemostatic material is specifically used, the S1 solution containing the component A and the S2 solution containing the component B and the photoinitiator can be injected simultaneously, the two components reach hemostatic positions simultaneously, and solid gel can be formed at normal body temperature (usually 10-40 ℃) of a human body or an animal, so that the rapid hemostatic material can be adhered to tissues to achieve a hemostatic effect.
The invention will be described in detail with reference to examples.
Example 1a hemostatic hydrogel suitable for use in multiple organs, comprising the following components in weight percent: 0.1mL of component A (accounting for 10 percent of the system), 0.1mL of component B (accounting for 20 percent of the system), 1 percent of photoinitiator and the balance of water. Wherein, the component A is cyclodextrin aldehyde; the component B is methacrylic acylated hyaluronic acid; the photoinitiator was 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionacetone, and the total dosage was 0.2mL.
The preparation method of the double-network hemostatic hydrogel comprises the following steps: dissolving the component A in water to obtain a solution S1; dissolving the component B and the photoinitiator in water to obtain a solution S2; and mixing and crosslinking the solution S1 and the solution S2 at normal temperature to form the double-component hemostatic hydrogel.
Example 2a hemostatic hydrogel suitable for use in multiple organs, comprising the following components in weight percent: 0.1mL of component A (accounting for 5 percent of the system), 0.1mL of component B (accounting for 10 percent of the system), 1 percent of photoinitiator and the balance of water. Wherein, the component A is cyclodextrin aldehyde; the component B is methacrylic acylated hyaluronic acid; the photoinitiator is as follows: 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionne in a total amount of 0.2mL.
The preparation method of the double-network hemostatic hydrogel comprises the following steps: dissolving the component A in water to obtain a solution S1; dissolving the component B and the photoinitiator in water to obtain a solution S2; and mixing and crosslinking the solution S1 and the solution S2 at normal temperature to form the double-component hemostatic hydrogel.
Example 3 a hemostatic hydrogel suitable for use in multiple organs, comprising the following components in weight percent: 0.1mL of component A (accounting for 10 percent of the system), 0.1mL of component B (accounting for 5 percent of the system), 1 percent of photoinitiator and the balance of water. Wherein, the component A is cyclodextrin aldehyde; the component B is methacrylic acylated hyaluronic acid; the photoinitiator is as follows: 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionne in a total amount of 0.2mL.
The preparation method of the double-network hemostatic hydrogel comprises the following steps: dissolving the component A in water to obtain a solution S1; dissolving the component B and the photoinitiator in water to obtain a solution S2; and mixing and crosslinking the solution S1 and the solution S2 at normal temperature to form the double-component hemostatic hydrogel.
Example 4A hemostatic hydrogel suitable for multiple organs comprises, in weight percent, 0.1mL of the A component (20% of the system), 0.1mL of the B component (5% of the system), 1% of the photoinitiator, and the balance water. Wherein, the component A is cyclodextrin aldehyde; the component B is methacrylic acylated hyaluronic acid; the photoinitiator is as follows: 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionne in a total amount of 0.2mL.
The preparation method of the double-network hemostatic hydrogel comprises the following steps: dissolving the component A in water to obtain a solution S1; dissolving the component B and the photoinitiator in water to obtain a solution S2; and mixing and crosslinking the solution S1 and the solution S2 at normal temperature to form the double-component hemostatic hydrogel.
Example 5A hemostatic hydrogel suitable for multiple organs comprises, in weight percent, 0.1mL of the A component (20% of the system), 0.1mL of the B component (10% of the system), 1% of the photoinitiator, and the balance water. Wherein, the component A is cyclodextrin aldehyde; the component is methacrylic acylated hyaluronic acid; wherein the photoinitiator is: 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionne in a total amount of 0.2mL.
The preparation method of the double-network hemostatic hydrogel comprises the following steps: dissolving the component A in water to obtain a solution S1; dissolving the component B and the photoinitiator in water to obtain a solution S2; and mixing and crosslinking the solution S1 and the solution S2 at normal temperature to form the double-component hemostatic hydrogel.
Example 6A hemostatic hydrogel suitable for multiple organs comprises, in weight percent, 0.1mL of the A component (10% of the system), 0.1mL of the B component (20% of the system), 3% of the photoinitiator, and the balance of water. Wherein, the component A is cyclodextrin aldehyde; the component B is methacrylic acylated hyaluronic acid; wherein the photoinitiator is: 2-hydroxy-4- (2-hydroxyethoxy) -2-methylpropionne in a total amount of 0.2mL.
The preparation method of the double-network hemostatic hydrogel comprises the following steps: dissolving the component A in water to obtain a solution S1; dissolving the component B and the photoinitiator in water to obtain a solution S2; and mixing and crosslinking the solution S1 and the solution S2 at normal temperature to form the double-component hemostatic hydrogel.
Comparative example 1 commercial domestic medical hydrogel was used in an amount of 0.5mL.
Test example 1 Performance test of hemostatic hydrogel
(1) Rapid hemostatic function
The practical application of the double-network rapid hemostatic hydrogel obtained in the embodiment 1 of the invention is shown in fig. 1, the position of a rat heart is selected as an experimental part, the heart is needled by a needle, a syringe A filled with an S1 solution containing an A component and a syringe B filled with an S2 solution containing a B component and a photoinitiator are rapidly injected into a wound at the same time, the two components reach a hemostatic part at the same time, a solid gel is formed, and the hemostatic effect is achieved by adhesion with tissues.
The hemostatic hydrogel of example 1 of the present invention was applied to five major solid organs of rats, and it was seen that solid gel was formed upon reaching the wound, and hemostasis was effected.
The gel time of the hemostatic water gel of the invention is measured, and as shown in table 1, the hemostatic hydrogel of the invention has a fast gel time and can achieve the effect of fast stopping bleeding.
TABLE 1 gel time test results
As can be seen from the data in the table 1, the double-network hemostatic water has shorter gelling time within 70s, and has excellent rapid hemostatic performance compared with the hemostatic hydrogel in the prior art which needs more than 120 s.
FIGS. 1-5 are tissue adhesive drawings showing hemostasis after use of example 1 of the present application. The wound is fast in stopping bleeding and healing, and has no inflammatory reaction. Fig. 7 is a photograph of the hemostatic sites of comparative example 1 after application of the commercial hemostatic hydrogel. As can be seen from the comparison of FIGS. 1 to 5 and FIG. 7, the hydrogel obtained in example 1 of the present application has smooth surface of the parenchymal organ, and the hydrogel film formed by the conventional hydrogel with large dosage is uneven, and the phenomenon of aggregation of the hydrogel occurs. And comparative example 1 was used in an amount significantly higher than that of the present application.
(2) Biological safety
FIG. 6 shows the cell activity of HUVEC and L929 used in example 1 of the present invention, which is seen to have good biosafety.
(3) Gel Strength Properties
Gel strength measurements were performed on the hemostatic hydrogels of the examples of the present invention, and the test results are shown in table 2.
TABLE 2 gel strength test results
As can be seen from the data in Table 2, the hemostatic water of the present invention has good gel strength, can withstand blood pressure from blood vessels inside a wound and pressure for assisting hemostasis outside the wound, can reach more than 200kPa, has certain adhesive strength, and has firm tissue adhesive force.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (4)
1. The hemostatic hydrogel is characterized by being prepared from the following raw materials in percentage by mass:
1-20% of aldehyde compound, 10-30% of methacrylamide compound, 0.1-2% of photoinitiator and the balance of water;
The aldehyde compound comprises at least one of anisaldehyde, polyaldehyde polyethylene glycol, cinnamaldehyde, vanillin and cyclodextrin aldehyde;
The methacrylamide compound comprises at least one of methacrylamide gelatin, methacrylamide hyaluronic acid, methacrylamide sodium alginate, methacrylamide glucose, methacrylamide chitosan, methacrylamide cellulose and methacrylamide carboxymethyl chitosan;
the photoinitiator is 2-hydroxy-4- (2-hydroxyethoxy) -2-methyl propiophenone;
the preparation method of the hemostatic hydrogel comprises the following steps:
Dissolving an aldehyde compound in water to obtain a solution S1;
Dissolving a methacrylamide compound and a photoinitiator in water to obtain a solution S2;
And mixing the solution S1 and the solution S2, and performing crosslinking reaction under the action of ultraviolet irradiation to obtain the hemostatic hydrogel.
2. The hemostatic hydrogel of claim 1, wherein the hydrogel is a gel,
The aldehyde group compound is cyclodextrin aldehyde.
3. The hemostatic hydrogel of claim 1, wherein the hydrogel is a gel,
The methacrylamide compound is methacrylamide hyaluronic acid.
4. The hemostatic hydrogel of claim 1, wherein the hydrogel is a gel,
The temperature of the crosslinking reaction is 10-40 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110843773.6A CN115671371B (en) | 2021-07-26 | 2021-07-26 | Hemostatic hydrogel and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110843773.6A CN115671371B (en) | 2021-07-26 | 2021-07-26 | Hemostatic hydrogel and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115671371A CN115671371A (en) | 2023-02-03 |
| CN115671371B true CN115671371B (en) | 2024-04-19 |
Family
ID=85044540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110843773.6A Active CN115671371B (en) | 2021-07-26 | 2021-07-26 | Hemostatic hydrogel and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115671371B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060188940A1 (en) * | 2005-02-22 | 2006-08-24 | Michael Cima | Combinatorial hydrogel formulation |
| CN111388748A (en) * | 2020-03-03 | 2020-07-10 | 东华大学 | Antibacterial and hemostatic multifunctional composite hydrogel dressing and preparation method thereof |
| CN111632189A (en) * | 2020-05-27 | 2020-09-08 | 深圳先进技术研究院 | Injectable hydrogel hemostatic based on marine-derived gelatin, and application method thereof |
-
2021
- 2021-07-26 CN CN202110843773.6A patent/CN115671371B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060188940A1 (en) * | 2005-02-22 | 2006-08-24 | Michael Cima | Combinatorial hydrogel formulation |
| CN111388748A (en) * | 2020-03-03 | 2020-07-10 | 东华大学 | Antibacterial and hemostatic multifunctional composite hydrogel dressing and preparation method thereof |
| CN111632189A (en) * | 2020-05-27 | 2020-09-08 | 深圳先进技术研究院 | Injectable hydrogel hemostatic based on marine-derived gelatin, and application method thereof |
Non-Patent Citations (2)
| Title |
|---|
| Blood-aggregating hydrogel particles for use as a hemostatic agent;Behrens, AM, 等;ACTA BIOMATERIALS;第10卷(第2期);第701-708页 * |
| Hemostatic properties of in situ gels composed of hydrophobically modified biopolymers;Mizuta, R, 等;JOURNAL OF BIOMATERIALS APPLICATIONS;第33卷(第2期);第315-323页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115671371A (en) | 2023-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liang et al. | Bioinspired injectable self-healing hydrogel sealant with fault-tolerant and repeated thermo-responsive adhesion for sutureless post-wound-closure and wound healing | |
| Zou et al. | Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing | |
| Qiao et al. | A mussel-inspired supramolecular hydrogel with robust tissue anchor for rapid hemostasis of arterial and visceral bleedings | |
| Liu et al. | Recent advances in materials for hemostatic management | |
| Lv et al. | Multi-crosslinked hydrogels with strong wet adhesion, self-healing, antibacterial property, reactive oxygen species scavenging activity, and on-demand removability for seawater-immersed wound healing | |
| Li et al. | Biodegradable microporous starch with assembled thrombin for rapid induction of hemostasis | |
| CN108912352A (en) | A kind of antibacterial adherency injection aquagel dressing and its preparation method and application | |
| WO2010059280A4 (en) | Fibrous tissue sealant and method of using same | |
| CN114767919B (en) | Hydrogel powder for rapid hemostasis as well as preparation method and application thereof | |
| CN103848926B (en) | A kind of preparation method of using carboxyl chitosan and purposes | |
| Yang et al. | Multifunctional wound dressing for rapid hemostasis, bacterial infection monitoring and photodynamic antibacterial therapy | |
| Zheng et al. | A novel pullulan oxidation approach to preparing a shape memory sponge with rapid reaction capability for massive hemorrhage | |
| WO2020134757A1 (en) | Medical sealing glue capable of promoting wound healing and preparation method therefor | |
| CN113372585A (en) | Preparation method and application of hydrogel with high-adhesion composite function | |
| CN113633817A (en) | In-situ polymerization strongly-adhered antibacterial hemostatic hydrogel and preparation method and application thereof | |
| CN110665051A (en) | Preparation method of hemostatic and antibacterial frozen gel stent | |
| CN112843325A (en) | Medical hydrogel adhesive and preparation method and application thereof | |
| Tian et al. | Strong biopolymer-based nanocomposite hydrogel adhesives with removability and reusability for damaged tissue closure and healing | |
| CN115400260A (en) | Repair gel containing recombinant humanized collagen and preparation method thereof | |
| Wu et al. | Strong tissue adhesive polyelectrolyte complex powders based on low molecular weight chitosan for acute hemorrhage control | |
| CN115671371B (en) | Hemostatic hydrogel and preparation method and application thereof | |
| US10137219B2 (en) | Coherent blood coagulation structure of water-insoluble chitosan and water-dispersible starch coating | |
| CN114887110B (en) | Hemostatic material capable of quickly stopping bleeding and preparation method thereof | |
| WO2024000861A1 (en) | Peg two-component self-adhesive absorbable biological mesh, method for preparing same, and use thereof | |
| Huang et al. | Natural polymer-based bioadhesives as hemostatic platforms for wound healing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |