CN109666151B - Injectable hydrogel capable of releasing hydrogen sulfide and preparation method thereof - Google Patents
Injectable hydrogel capable of releasing hydrogen sulfide and preparation method thereof Download PDFInfo
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- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
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- C—CHEMISTRY; METALLURGY
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- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
- C08J2405/04—Alginic acid; Derivatives thereof
Abstract
The invention provides an injectable hydrogel capable of releasing hydrogen sulfide and a preparation method thereof, wherein hydroxyl on sodium Alginate (ALG) is oxidized into aldehyde group to obtain partially oxidized sodium alginate (ADA), and the aldehyde group is utilized to react with amino on 2-aminopyridine-5-thiocarbamide (APTA) to graft 2-aminopyridine-5-thiocarbamide on the partially oxidized sodium alginate to obtain a macromolecular cross-linking agent with aldehyde group capable of releasing hydrogen sulfide, namely the partially oxidized sodium alginate-2-aminopyridine-5-thiocarbamide (ADA-APTA). Partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide (ADA-APTA) and gelatin are blended to obtain the alginate-based injectable hydrogel capable of releasing hydrogen sulfide. The preparation method of the gel is simple, the reaction condition is mild, the biocompatibility is good, and the amount of hydrogen sulfide released by the gel can be adjusted by controlling the grafting rate of the 2-aminopyridine-5-thiocarboxamide.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to preparation of alginate-based injectable hydrogel capable of releasing hydrogen sulfide.
Background
Sodium alginate is a byproduct after extracting iodine and mannitol from brown algae such as kelp or gulfweed, and its molecules are connected by a (1 → 4) bond between beta-D-mannuronic acid (M) and alpha-L-guluronic acid (alpha-L-guluronic acid, G). The sodium alginate contains a large amount of-COO-, can show polyanion behavior in aqueous solution, has certain adhesiveness, and can be used as a drug carrier for treating mucosal tissues.
Under the acidic condition, the-COO-is converted into-COOH, the ionization degree is reduced, the hydrophilicity of the sodium alginate is reduced, molecular chains are shrunk, when the pH value is increased, the-COOH groups are continuously dissociated, the hydrophilicity of the sodium alginate is increased, and the molecular chains are stretched. Therefore, sodium alginate has significant pH sensitivity.
Sodium alginate can rapidly form gel under extremely mild conditions, when cations such as Ca2+, Sr2+ and the like exist, Na + on G units and divalent cations generate ion exchange reaction, and the G units are stacked to form a cross-linked network structure, so that hydrogel is formed. The gel forming condition of the sodium alginate is mild, which can avoid the inactivation of active substances such as sensitive medicines, proteins, cells, enzymes and the like.
Hydrogen sulfide is a colorless and toxic gas with a strong odor of rotten eggs. However, recent studies have shown that it is also a novel class of gas signaling molecules and cytoprotectants. Is a third gaseous medium following Nitric Oxide (NO), carbon monoxide (CO). H2S is involved in regulating homeostasis of various physiological systems including cardiovascular, neuronal, gastrointestinal, renal, hepatic and reproductive systems. The regulated level of intracellular H2S has a profound effect on disease biology. Therefore, the method of controlling generation and dissipation is important.
Researchers have attempted to release hydrogen sulfide in organisms using hydrogen sulfide donors, such as sodium hydrosulfide, but these small molecule hydrogen sulfide donors can only release hydrogen sulfide rapidly in a short time and the process is not controllable. There is therefore an urgent need for donors that can generate hydrogen sulfide slowly and over a longer period of time. The 2-aminopyridine-5-thiocarboxamide involved in the invention can slowly and controllably generate hydrogen sulfide gas under the stimulation of sulfydryl.
Disclosure of Invention
The invention overcomes the defects in the prior art and provides an injectable hydrogel capable of releasing hydrogen sulfide and a preparation method thereof, wherein 2-aminopyridine-5-thiocarboxamide capable of generating hydrogen sulfide under the stimulation of sulfydryl is grafted to partially oxidized sodium alginate by utilizing the reaction of amino and aldehyde group to generate schiff base, so that the alginate-based injectable hydrogel capable of releasing hydrogen sulfide is prepared.
The purpose of the invention is realized by the following technical scheme.
An injectable hydrogel capable of releasing hydrogen sulfide is prepared by oxidizing hydroxyl on sodium Alginate (ALG) into aldehyde group to obtain partially oxidized sodium alginate (ADA), grafting 2-aminopyridine-5-thiocarboxamide onto the partially oxidized sodium alginate by utilizing the reaction of the aldehyde group and amino on 2-aminopyridine-5-thiocarboxamide (APTA) to obtain a macromolecular cross-linking agent capable of releasing hydrogen sulfide and provided with the aldehyde group to partially oxidize the sodium alginate-2-aminopyridine-5-thiocarboxamide (ADA-APTA), and blending the ADA-APTA and gelatin to obtain the injectable hydrogel capable of releasing hydrogen sulfide; wherein the mass ratio of the partially oxidized sodium alginate (ADA) to the 2-aminopyridine-5-thiocarbamide (APTA) is (8-12): (1-2), the mass ratio of ADA-TA to gelatin is (1-2): 5.
the mass ratio of the partially oxidized sodium alginate (ADA) to the 2-aminopyridine-5-thiocarbamide (APTA) is 10: 1.
the mass ratio of ADA-APTA to gelatin is 1: 5.
a method for preparing an injectable hydrogel that releases hydrogen sulfide, comprising the steps of:
step 1, adding sodium alginate into absolute ethyl alcohol, stirring until the sodium alginate is uniformly dispersed, adding sodium periodate into deionized water, stirring in the dark until the sodium periodate is completely dissolved, pouring a sodium periodate solution into a sodium alginate suspension, reacting at the room temperature of 20-25 ℃ for 2-4 hours, adding 4-6ml of ethylene glycol into the reaction system to terminate the reaction for 10-20min, pouring the reaction solution into a dialysis bag, dialyzing with deionized water for 2-4 days, and freeze-drying the dialyzed product to obtain white foam partially oxidized sodium alginate (ADA);
the synthesis principle of oxidized sodium alginate is as follows:
step 2, dissolving the partially oxidized sodium alginate (ADA) prepared in the step 1 in deionized water, adding a dispersing agent into the deionized water, stirring the mixture until the mixture is uniformly dispersed, placing 2-aminopyridine-5-thiocarboxamide (APTA) in the dispersing agent, stirring the mixture until the mixture is uniformly dispersed, dropwise adding the 2-aminopyridine-5-thiocarboxamide (APTA) dispersion into the ADA dispersion at a dropping rate of 3 to 5 drops/min, reacting at 40 to 60 ℃ for 3 to 6 hours under an anaerobic condition, performing suction filtration, pouring the filtrate into absolute ethyl alcohol, placing the mixture in a refrigerator for 8 to 12 hours, centrifuging and drying the mixture to obtain light yellow partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide (ADA-APTA), wherein the chemical formula of the ADA-APTA is as follows:
and 3, preparing a 2-5 wt% aqueous solution from partially oxidized sodium alginate-2-aminopyridine-5-thiocarbamide (ADA-APTA), preparing a 4-8 wt% aqueous solution from gelatin, blending according to the mass ratio of (1-2) to 5, and swirling to uniformly mix the reaction solution to obtain the injectable hydrogel capable of releasing the hydrogen sulfide.
In the step 1, the mass ratio of sodium alginate to sodium periodate is (2-4): (1-2), preferably 2: 1.
In the step 1, sodium periodate solution is poured into sodium alginate suspension, and after reaction for 4 hours at room temperature of 20-25 ℃, 5ml of ethylene glycol is added into the reaction system to terminate the reaction for 15 min.
In the step 1, the replacement frequency of the ionized water is 6-8 h/time in the ionized water dialysis.
In step 2, the mass ratio of partially oxidized sodium alginate (ADA) to 2-aminopyridine-5-thiocarbamide (APTA) is (8-12): (1-2), preferably 10: 1.
In the step 2, dimethyl sulfoxide (DMSO) or N, N-Dimethylformamide (DMF) is adopted as a dispersing agent; inert shielding gas is used to provide oxygen-free conditions for the reaction system, such as nitrogen, helium or argon.
In the step 3, the mass ratio of ADA-APTA to gelatin is 1:5, and the gelling time is 10-15min when the pH value is 7 at the room temperature of 20-25 ℃; gelling time is 2-5min at 37-40 deg.C and pH 8.
The responsiveness of 2-aminopyridine-5-thiocarboxamide to thiol was examined: 10mg of APTA was dissolved in 1ml of absolute ethanol, and diluted to 3ml with 2ml of deionized water to prepare a reaction solution. And (3) continuously heating the reaction solution in a water bath at 37 ℃, detecting the release condition of the hydrogen sulfide by using lead acetate test paper, adding cysteine, and continuously observing the color change of the lead acetate test paper.
FIG. 1 shows APTA13C-NMR spectrum, as can be seen from the spectrum, 188ppm is absorption peak of carbon atom on thioamide group, 109ppm, 139ppm, 126ppm, 151ppm, 162ppm are absorption peak of carbon atom on pyridine ring respectively, wherein 188ppm amide peak is very obvious, and the structural characteristics of APTA can be basically judged by nuclear magnetic carbon spectrum.
FIG. 2 is a comparison graph of ultraviolet spectra of partially oxidized sodium alginate (ADA), 2-aminopyridine-5-thiocarboxamide (APTA), and partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide (ADA-APTA), from which it can be seen that ADA has no absorption peak, while ADA-APTA grafted with 2-aminopyridine-5-thiocarboxamide has the same absorption peak as APTA, and thus it can be judged that APTA grafting is successful.
Preparing a 2-5 wt% aqueous solution from partially oxidized sodium alginate-2-aminopyridine-5-thiocarbamide (ADA-APTA), preparing a 4-8 wt% aqueous solution from gelatin, and blending according to a mass ratio of 1:5 to obtain the hydrogen sulfide releasing injectable hydrogel. The hydrogen sulfide-releasing injectable gel appeared pale yellow and opaque due to grafting of 2-aminopyridine-5-carbothioamide (APTA). The product is soft and elastic, and has viscosity and weak fluidity. It is worth noting that, because the gel has weak mechanical properties and weak fluidity after gelling, the gel can be injected not only in the form of solution, but also after gelling, therefore, the gel has no strict requirement on gelling time in clinical application, and can be injected before or after gelling according to the requirement, which is also a favorable improvement to the strict requirement on gelling time of the existing injectable gel.
The invention has the beneficial effects that: the preparation method of the gel is simple, the reaction condition is mild, the biocompatibility is good, and the amount of hydrogen sulfide released by the gel can be adjusted by controlling the grafting rate of the 2-aminopyridine-5-thiocarboxamide.
Drawings
FIG. 1 shows APTA13A C-NMR spectrum;
FIG. 2 is a graph comparing UV spectra of partially oxidized sodium alginate (ADA), 2-aminopyridine-5-carbothioamide (APTA), and partially oxidized sodium alginate-2-aminopyridine-5-carbothioamide (ADA-APTA);
FIG. 3 is a graph comparing a 3 wt% aqueous solution of ADA-APTA with a gel.
Detailed Description
The technical solution of the present invention is further illustrated by the following specific examples.
The drugs used in the examples are shown in the following table:
| medicine and food additive | Manufacturer of the product |
| Sodium alginate | Yueli chemical Co Ltd of Tianjin City |
| Sodium periodate | Kalimet chemical technology Co Ltd |
| 2-Aminopyridine-5-thiocarboxamides | TIANJIN KWANGFU FINE CHEMICAL INDUSTRY Research Institute |
| Gelatin | TIANJIN SUSITAILAI BIOTECHNOLOGY Co.,Ltd. |
| Dimethyl sulfoxide | TIANJIN KWANGFU FINE CHEMICAL INDUSTRY Research Institute |
| N, N-dimethylformamide | SAEN CHEMICAL TECHNOLOGY (SHANGHAI) Co.,Ltd. |
| Liquid nitrogen | TIANJIN ZHENHAO TECHNOLOGY Co.,Ltd. |
| Acetone (II) | Yueli chemical Co Ltd of Tianjin City |
The instruments used in the examples are shown in the following table:
example 1
The preparation of alginate-based injectable hydrogels capable of releasing hydrogen sulfide is illustrated by the example of an oxidation degree of 50% and a feed ratio of 2-aminopyridine-5-thiocarboxamide of 10%.
5.0g of sodium alginate is weighed and added into 25ml of absolute ethyl alcohol, and stirred until the mixture is uniformly dispersed. 2.67g of sodium periodate is weighed and added into 25ml of deionized water, and the mixture is stirred in the dark until the sodium periodate is completely dissolved (the sodium periodate is easy to be decomposed by light, so the sodium periodate needs to be stirred in the dark, and the reaction needs to be carried out in the dark). Sodium periodate was poured into the suspension of sodium alginate and reacted at room temperature for 4 h. After 4h, 5ml of ethylene glycol was added to terminate the reaction for 15 min. Pouring the reaction solution into a dialysis bag, dialyzing with deionized water for three days, and changing dialysis water every day for about 3-4 times every day. The dialyzed product was lyophilized to give a white foam.
0.5g ADA was dissolved in 5ml deionized water and stirred until well dispersed. 5mg of 2-aminopyridine-5-thiocarboxamide is dissolved in 5ml of absolute ethyl alcohol, after the complete dissolution, 5ml of deionized water is added to dilute the solution to 10ml, the solution is added into ADA solution, nitrogen is introduced to remove oxygen in the system, and the reaction is carried out for 4h at 50 ℃. And after the reaction is finished, filtering to obtain filtrate, pouring the filtrate into 60ml of absolute ethyl alcohol, putting the filtrate into a refrigerator for overnight, centrifuging the filtrate the next day, taking the lower-layer solid, and drying the solid to obtain a light yellow product ADA-APTA.
Preparing ADA-APTA into 3 wt% aqueous solution, preparing gelatin into 5 wt% aqueous solution, blending according to the volume ratio of 1:1, and stirring to obtain gel.
Example 2
The preparation of alginate-based injectable hydrogel capable of releasing hydrogen sulfide is illustrated by taking the example that the oxidation degree of sodium alginate is 50% and the feeding ratio of 2-aminopyridine-5-thiocarboxamide is 20%.
5.0g of sodium alginate is weighed and added into 25ml of absolute ethyl alcohol, and stirred until the mixture is uniformly dispersed. 2.67g of sodium periodate is weighed and added into 25ml of deionized water, and the mixture is stirred in the dark until the sodium periodate is completely dissolved (the sodium periodate is easy to be decomposed by light, so the sodium periodate needs to be stirred in the dark, and the reaction needs to be carried out in the dark). Sodium periodate was poured into the suspension of sodium alginate and reacted at room temperature for 4 h. After 4h, 5ml of ethylene glycol was added to terminate the reaction for 15 min. Pouring the reaction solution into a dialysis bag, dialyzing with deionized water for three days, and changing dialysis water every day for about 3-4 times every day. The dialyzed product was lyophilized to give a white foam.
0.5g ADA was dissolved in 5ml deionized water and stirred until well dispersed. Dissolving 10mg of 2-aminopyridine-5-thiocarboxamide in 5ml of absolute ethyl alcohol, adding 5ml of deionized water to dilute the solution to 10ml after the solution is fully dissolved, adding the solution into ADA solution, introducing nitrogen to remove oxygen in the system, and reacting for 4 hours at 50 ℃. And after the reaction is finished, filtering to obtain filtrate, pouring the filtrate into 60ml of absolute ethyl alcohol, putting the filtrate into a refrigerator for overnight, centrifuging the filtrate the next day, taking the lower-layer solid, and drying the solid to obtain a light yellow product ADA-APTA.
Preparing ADA-APTA into 3 wt% aqueous solution, preparing gelatin into 5 wt% aqueous solution, blending according to the volume ratio of 1:1, and stirring to obtain gel.
The grafting rate can be changed by changing the charge ratio of the 2-aminopyridine-5-thiocarboxamide under the condition that the oxidation degree of sodium alginate is not changed, generally, the higher the grafting rate is, the more the amount of hydrogen sulfide released by gel is, the faster the release rate is, but because the 2-aminopyridine-5-thiocarboxamide has certain rigidity, when the grafting rate reaches a certain value, the grafting rate cannot be continuously improved due to steric hindrance, the charge ratio of the 2-aminopyridine-5-thiocarboxamide selected in the text is 20%, the obtained grafting rate is about 10%, the grafting efficiency is 50%, and in practical application, the grafting rate of the 2-aminopyridine-5-thiocarboxamide can be adjusted according to the required concentration of hydrogen sulfide, so that the required release amount of hydrogen sulfide is achieved. The concentration of exogenous hydrogen sulfide used for treatment in organisms is generally in the order of mum, but because the release efficiency of hydrogen sulfide in organisms is low and the half-life of hydrogen sulfide is only tens of seconds to a few minutes, the concentration of 2-aminopyridine-5-thiocarboxamide in hydrogel generally reaches the order of nm.
The gelling temperature and pH value can be adjusted, and the gelling time can be adjusted. Herein, the gel forming time is 10-15min at room temperature (20-25 ℃) and pH 7. At 37-40 deg.c and pH 8, the gelling time is 2-5 min. The practical application can be adjusted according to the requirements.
Preparing a 2-5 wt% aqueous solution from partially oxidized sodium alginate-2-aminopyridine-5-thiocarbamide (ADA-APTA), preparing a 4-8 wt% aqueous solution from gelatin, and blending according to a mass ratio of 1:5 to obtain the hydrogen sulfide releasing injectable hydrogel. The hydrogen sulfide-releasing injectable gel appeared pale yellow and opaque due to grafting of 2-aminopyridine-5-carbothioamide (APTA). The product is soft and elastic, and has viscosity and weak fluidity. It is worth noting that, because the gel has weak mechanical properties and weak fluidity after gelling, the gel can be injected not only in the form of solution, but also after gelling, therefore, the gel has no strict requirement on gelling time in clinical application, and can be injected before or after gelling according to the requirement, which is also a favorable improvement to the strict requirement on gelling time of the existing injectable gel.
The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.
Claims (13)
1. An injectable hydrogel that releases hydrogen sulfide, characterized by: oxidizing hydroxyl on sodium alginate into aldehyde group to obtain partially oxidized sodium alginate, grafting 2-aminopyridine-5-thiocarboxamide onto the partially oxidized sodium alginate by utilizing the reaction of the aldehyde group and amino on 2-aminopyridine-5-thiocarboxamide to obtain a macromolecular cross-linking agent which has the aldehyde group and can release hydrogen sulfide, partially oxidizing the sodium alginate-2-aminopyridine-5-thiocarboxamide, and blending the partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide and gelatin to obtain injectable hydrogel which can release the hydrogen sulfide; wherein the mass ratio of the partially oxidized sodium alginate to the 2-aminopyridine-5-thiocarboxamide is (8-12): (1-2), the mass ratio of the partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide to the gelatin is (1-2): 5.
2. the injectable hydrogel of claim 1, wherein said injectable hydrogel releases hydrogen sulfide, and wherein said injectable hydrogel comprises: the mass ratio of the partially oxidized sodium alginate to the 2-aminopyridine-5-thiocarboxamide is 10: 1.
3. the injectable hydrogel of claim 1, wherein said injectable hydrogel releases hydrogen sulfide, and wherein said injectable hydrogel comprises: the mass ratio of the partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide to the gelatin is 1: 5.
4. a method for preparing an injectable hydrogel that releases hydrogen sulfide, characterized in that: the method comprises the following steps:
step 1, adding sodium alginate into absolute ethyl alcohol, stirring until the sodium alginate is uniformly dispersed, adding sodium periodate into deionized water, stirring in a dark place until the sodium periodate is completely dissolved, pouring a sodium periodate solution into a sodium alginate suspension, reacting at the room temperature of 20-25 ℃ for 2-4 hours, adding 4-6ml of ethylene glycol into the reaction system to terminate the reaction for 10-20min, pouring the reaction solution into a dialysis bag, dialyzing with deionized water for 2-4 days, and freeze-drying the dialyzed product to obtain white foam partially oxidized sodium alginate;
step 2, dissolving the partially oxidized sodium alginate prepared in the step 1 in deionized water, adding a dispersing agent into the deionized water, stirring the mixture until the mixture is uniformly dispersed, placing 2-aminopyridine-5-thiocarboxamide in the dispersing agent, stirring the mixture until the mixture is uniformly dispersed, dropwise adding the 2-aminopyridine-5-thiocarboxamide dispersion liquid into the partially oxidized sodium alginate dispersion liquid at the dropping speed of 3-5 drops/min, reacting the mixture for 3-6 hours at 40-60 ℃ under an anaerobic condition, performing suction filtration, pouring the filtrate into absolute ethyl alcohol, placing the mixture in a refrigerator for 8-12 hours, centrifuging and drying the mixture to obtain light yellow partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide;
and 3, preparing the partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide into a 2-5 wt% aqueous solution, preparing gelatin into a 4-8 wt% aqueous solution, blending according to the mass ratio of (1-2) to 5, and swirling to uniformly mix reaction liquid to obtain the injectable hydrogel capable of releasing the hydrogen sulfide.
5. The method for preparing an injectable hydrogel capable of releasing hydrogen sulfide according to claim 4, wherein: in the step 1, the mass ratio of sodium alginate to sodium periodate is (2-4): (1-2).
6. The method of claim 5 for the preparation of an injectable hydrogel that releases hydrogen sulfide, wherein: in step 1, the mass ratio of sodium alginate to sodium periodate is 2: 1.
7. The method for preparing an injectable hydrogel capable of releasing hydrogen sulfide according to claim 4, wherein: in the step 1, sodium periodate solution is poured into sodium alginate suspension, and after reaction for 4 hours at room temperature of 20-25 ℃, 5ml of ethylene glycol is added into the reaction system to terminate the reaction for 15 min; in the ionized water dialysis, the replacement frequency of the ionized water is 6-8 h/time.
8. The method for preparing an injectable hydrogel capable of releasing hydrogen sulfide according to claim 4, wherein: in the step 2, the mass ratio of the partially oxidized sodium alginate to the 2-aminopyridine-5-thiocarboxamide is (8-12): (1-2).
9. The method of claim 8, wherein the injectable hydrogel is selected from the group consisting of: in step 2, the mass ratio of the partially oxidized sodium alginate to the 2-aminopyridine-5-thiocarboxamide is 10: 1.
10. The method for preparing an injectable hydrogel capable of releasing hydrogen sulfide according to claim 4, wherein: in the step 2, dimethyl sulfoxide or N, N-dimethylformamide is adopted as a dispersing agent; inert shielding gas is used to provide oxygen-free conditions for the reaction system.
11. The method of claim 10 for preparing an injectable hydrogel that releases hydrogen sulfide, wherein: in step 2, nitrogen, helium or argon is used as the inert protective gas.
12. The method for preparing an injectable hydrogel capable of releasing hydrogen sulfide according to claim 4, wherein: in the step 3, the mass ratio of the partially oxidized sodium alginate-2-aminopyridine-5-thiocarboxamide to the gelatin is 1:5, and the gelling time is 10-15min at room temperature of 20-25 ℃ and when the pH value is 7; gelling time is 2-5min at 37-40 deg.C and pH 8.
13. Use of an injectable hydrogel releasing hydrogen sulfide as claimed in any of claims 1 to 3 for the preparation of an injectable hydrogen sulfide releasing material, characterized in that: the gel has weak mechanical property and weak fluidity after being gelatinized, and can be injected in a solution form and also can be injected after being gelatinized.
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| CN110755366A (en) * | 2019-09-27 | 2020-02-07 | 上海市第六人民医院 | Conductive oxidized sodium alginate hydrogel and preparation method thereof |
| CN111000979B (en) * | 2019-12-04 | 2022-11-25 | 南京师范大学 | Hydrogen sulfide donor based on keratin and synthesis method and application thereof |
| CN115120777B (en) * | 2021-03-26 | 2022-12-30 | 武汉理工大学 | Preparation method of nerve conduit capable of releasing hydrogen sulfide in response to active oxygen |
| CN113230269B (en) * | 2021-05-11 | 2022-02-01 | 中国科学院高能物理研究所 | Radiotherapy protective agent and preparation method and application thereof |
| CN114099419B (en) * | 2021-11-19 | 2023-03-24 | 苏州大学 | Sodium hydrosulfide-loaded injectable nano-fibrosis hydrogel and preparation method and application thereof |
| CN115737913B (en) * | 2022-10-18 | 2023-11-24 | 东莞市人民医院 | Controllable release H 2 S heart patch and preparation method and application thereof |
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| Arylthioamides as H2S Donors: L‑Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo;Alma Martelli,et al;《ACS MEDICINAL CHEMISTRY LETTERS》;20130808;第4卷(第10期);全文 * |
| Design of a Novel Composite H2S-Releasing Hydrogel for Cardiac Tissue Repair;Mauretti Arianna,et al;《MACROMOLECULAR BIOSCIENCE》;20160209;第16卷(第6期);全文 * |
| 新型海藻酸盐-明胶水凝胶的研究;孙言蓓;《中国优秀硕士学位论文全文数据库医药卫生科技辑》;20090415(第4期);全文 * |
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