阅读说明：本技术 一种用于创伤修复的有机-无机杂化敷料及其制备方法和应用 (A kind of hybrid inorganic-organic dressing and its preparation method and application for wound repair ) 是由 王晶 张全斌 耿丽华 岳洋 张虹 吴宁 于 2019-09-04 设计创作，主要内容包括：本发明提供了一种用于创伤修复,特别是慢性创伤修复的有机-无机杂化敷料及其制备方法和应用。更具体的涉及到一种天然硫酸多糖在硅烷偶联剂的作用下修饰二氧化硅制备得到的一种有机-无机杂化纳米敷料,其通过溶胶-凝胶技术制备而成。本发明敷料制备方法简单易行,所制得的生物敷料具有良好的生物相容性,无细胞毒性,可以吸附炎症因子,促进细胞迁移和血管生成,促进慢性伤口愈合的作用。本发明特别适用于临床广泛存在的慢性难愈合伤口,特别是糖尿病溃疡的治疗与护理。(The present invention provides a kind of hybrid inorganic-organic dressing and its preparation method and application for being used for wound repair, especially chronic trauma reparation.It more particularly relates to a kind of puritan filler polysaccharide modify a kind of inorganic-organic hybridization nano dressing that silica is prepared under the action of silane coupling agent, be prepared by sol-gel technique.Dressing preparation method of the present invention is simple and easy, and obtained biological dressing has good biocompatibility, and no cytotoxicity can adsorb inflammatory factor, promotes cell migration and angiogenesis, promotes the effect of chronic wound care.The present invention is especially suitable for the chronic Hard agglut wound that clinic is widely present, the especially treatments and nursing of diabetic ulcer.)

1. a kind of hybrid inorganic-organic dressing for wound repair, which is characterized in that the hybrid inorganic-organic dressing by Algal polysaccharide sulfate modifies a kind of inorganic-organic hybridization nano dressing that silica is prepared under silane coupling agent, The silane coupling agent is 3- glycidyl ether oxypropyltrimethoxysilane.

2. a kind of hybrid inorganic-organic dressing for wound repair according to claim 1, which is characterized in that described Algal polysaccharide sulfate is from one of following or a variety of, marine brown kelp, sargassum thunbergii, thallus laminariae, sargassum fusifome, Mo Jiao The algal polysaccharide sulfate of one of algae etc. or a variety of brown algas, or from one of sea cucumber, sea urchin etc. or a variety of Algal polysaccharide sulfate in the echinoderm of ocean, algal polysaccharide sulfate include that sulfate content is 15-35%, fucose Content is 15-35%, molecular weight ranges 5-350kD.

3. a kind of preparation method of the hybrid inorganic-organic dressing as claimed in claim 1 or 2 for wound repair, feature exist In the hybrid inorganic-organic dressing is prepared in accordance with the following methods:

(1) it weighs algal polysaccharide sulfate to be completely dissolved in deionized water, stirring evenly and mass concentration is made is that 1-8% brown alga is more Sugar sulfate solution, preferred mass concentration is 4%, with 4M NaOH tune pH 6-9, preferably pH 7-8；

(2) 3- glycidyl ether oxypropyltrimethoxysilane is added dropwise, makes final concentration of 1-3%, preferably 2%, reaction temperature It is 15-40 DEG C, preferably 25 DEG C, reaction time 10-24h, reacts 17h；

(3) after reacting (2), tetramethoxy-silicane (TMOS) is added in the solution, makes final concentration of 1-3%, preferably 2%, Reaction temperature is 15-40 DEG C, and preferably 25 DEG C, reaction time 10-48h, reaction is for 24 hours；

(4) after completion of the reaction, it is precipitated with 95% ethyl alcohol, makes final ethyl alcohol mass concentration 60-80%, preferably 72%, it will Hybrid inorganic-organic dressing is made in 50-60 DEG C of drying 10-24h in deposit.

4. the application described in a kind of claim 1 for the hybrid inorganic-organic polysaccharide dressing of wound repair, it is characterised in that: The hybrid inorganic-organic dressing is applied in the application controlled in agent in the external application of wound repair, especially chronic trauma reparation.

5. application according to claim 4, it is characterised in that: the chronic trauma refers to diabetes caused by diabetes Sufficient or chronic refractory conjunction ulcer.

Technical field

The present invention relates to medical material tech fields, and in particular to one kind for wound repair, (especially repair by chronic trauma Hybrid inorganic-organic dressing and its preparation method and application again).

Background technique

Diabetes are the common diseases as caused by h and E factor interaction, clinical to be marked with hyperglycemia to be main Will, common sympton have more drinks, diuresis, more foods and syntexis etc..International Diabetes Federation in 2018 is disclosing the whole world the 8th edition Diabetes map.The results show that global diabetes adult patient (20-79 years old) has reached from 1.51 hundred million in 2000 by 2017 To 4.25 hundred million, increase nearly 2 times.It expects 2045, diabetic is likely to be breached 6.29 hundred million.Existing 4.25 hundred million diabetes in the whole world Patient, in All Countries, diabetes mellitus in China burden is most heavy, and patient numbers (1.14 hundred million) account for the whole world nearly 27%.Data show, entirely Just there is 1 to suffer from diabetes in every 11 adults of ball, but there is the diabetic of nearly half not obtain and make a definite diagnosis.According to the World Health Organization Statistics, diabetic complication are up to more than 100 kinds, are to be currently known a kind of most disease of complication, diabetes, diabetogenous nephrosis The complication such as disease, diabetic cerebrovascular disease usually annoying patient, these complication once occur, drug therapy be difficult it is inverse Turn.

Wound healing caused by diabetes is damaged and chronic non-healing ulcer of foot is the severe complication of diabetic. Root is it is estimated that the patient of all limbs amputation there are about 50%-70% is as caused by diabetic foot ulcer.About 15% glycosuria Patient suffer from diabetic keratopathy extremity ulcer, this be patient be hospitalized and amputation maximum reason.It is reported that in worldwide It is interior, in every 30 seconds, just there is a patient since diabetic foot ulcer causes one leg by amputation.Research shows that diabetes are burst The reason of ulcer does not recover for a long time mainly has at following 4 points: 1. not controlled inflammation, the bacteria planting at wound damage repeatedly；2. sugar Chronic ischemia, anoxic caused by the big blood vessel of urine disease and microangiopathies；3. diabetic foot ulcer easily causes the sense of deep tissue Dye, necrosis cause healing difficult；4. immune system also plays whole work during diabetic foot ulcer wound healing With cell factor, lymphokine and growth factor secretion increase in wound tissue, and that there are immune functions is disorderly by diabetic Disorderly, the healing of wound is influenced.

In treatment diabetes refractory skin wound, blood glucose, anti-infective, reinforced battalion are such as controlled in addition to carrying out systemic therapy It supports outside the measures of grade, positive wound care promotes its healing to occupy an important position in the treatment.Currently, domestic be clinically mostly used Chemistry for Chinese Traditional Medicine paste, antibiotic etc. treat the surface of a wound, scarce but that there are dressing change frequencies is more, wound healing is slow, is also easy to produce drug resistance etc. Point.Researcher develops a variety of for treating the dressing of diabetes chronic wound at present, mainly there is German conspicuous Mann's exploitation Interactive dressing containing polyacrylate and polyurethane polymer, the dressing of silicon rubber containing hydrophilic, alginic acid are fine It ties up and containing polysaccharide dressing such as chitosan, modification of polysaccharides, Heparan sulfates.Clinical test shows algin and chitosan medical Dressing has good curative effect for skin wounds wounds such as burns.It, will also be for sugar but for diabetes chronic wound healing Sick chronic wounds pathogenesis is urinated, more targeted remedy measures are provided.

Organic and inorganic in hybrid inorganic-organic materials there are organic-inorganic molecule interpenetrating networks or to be covalently keyed Molecule interference networks, organic component and inorganic component can interact in molecular scale, and apparent phase interface is not present.It is this Structure can be effectively combined the advantages of organic polymer (low, excellent in cushion effect and workability of flexibility, density etc.) and The characteristic of inorganic material (mechanical strength is high, resistant to chemical etching, thermal stability is good etc.).Compared with conventional composite materials, hydridization material Organic active force between inorganic component in material substantially enhances, and can integrate organic material and inorganic material to the maximum extent The advantages of, show novel excellent performance.Hybrid inorganic-organic materials have huge in the application of field of biomedicine Potentiality.Sol-gel method craft is mature simple, and poly-condensation and hydrolysis condition can be adjusted, and entire reaction process Mildly, the destruction caused by organic component of extreme reaction condition is avoided, is that synthesizing organic-inorganic hybrid material is most common Method.

Algal polysaccharide sulfate (FPS) is a kind of sulfated polysaccharides being mainly made of fucose, and height has been established in seminar The technology of preparing of purity algal polysaccharide sulfate, discovery is oral or injection FPS is to diabetes has obvious therapeutic action, can be with Blood glucose in diabetic mice concentration is significantly improved, Claudication states are mitigated, inhibits the ulcer and gangrene of mouse foot, improves lower extremity blood flow, Promote skeletal muscle angiogenesis, reduce endothelial cell inflammation, is the drug of very promising treatment diabetes.It is more in view of brown alga Sugar sulfate can effectively inhibit diabetic foot ulcer and gangrene in oral or injection administration, and FPS is made into diabetes chronic Wound biological dressing will have good potentiality.

Summary of the invention

In view of the deficiencies of the prior art, the present invention provides a kind of having for wound repair (especially chronic trauma reparation) Machine-inorganic hybridization dressing and its preparation method and application.

To achieve the above object, the technical solution adopted by the present invention is that: a kind of hybrid inorganic-organic for wound repair Dressing and its preparation method and application, the hybrid inorganic-organic dressing is by algal polysaccharide sulfate, 3- glycidol ether oxygroup Propyl trimethoxy silicane, silica crosslinking obtain, and the hybrid inorganic-organic dressing has wound repairing activity, described The application of hybrid inorganic-organic dressing refers to hybrid inorganic-organic dressing in wound repair (especially chronic trauma reparation) Application.

Wherein, the algal polysaccharide sulfate is from one of following or a variety of, marine brown kelp, rat-tail The algal polysaccharide sulfate of one of algae, thallus laminariae, sargassum fusifome, bladder-wrack etc. or a variety of brown algas, or from sea cucumber, Algal polysaccharide sulfate in one of sea urchin etc. or a variety of ocean echinoderms, algal polysaccharide sulfate includes sulfate Content is 15-35%, fucose content 15-35%, molecular weight ranges 5-350kD.

Wherein, the hybrid inorganic-organic dressing is prepared in accordance with the following methods:

(1) it weighs algal polysaccharide sulfate to be completely dissolved in deionized water, stirring evenly and mass concentration is made is that 1-8% is brown Polysaccharides sulphate solution, preferred mass concentration is 4%, with 4M NaOH tune pH 6-9, preferably pH 7-8；

(2) 3- glycidyl ether oxypropyltrimethoxysilane is added dropwise, makes final concentration of 1-3%, preferably 2%, reacts Temperature is 15-40 DEG C, preferably 25 DEG C, reaction time 10-24h, reacts 17h；

(3) after reacting (2), tetramethoxy-silicane (TMOS) is added in the solution, makes final concentration of 1-3%, preferably 2%, reaction temperature is 15-40 DEG C, and preferably 25 DEG C, reaction time 10-48h, reaction is for 24 hours；

(4) after completion of the reaction, it is precipitated with 95% ethyl alcohol, makes final ethyl alcohol mass concentration 60-80%, preferably 72%, by deposit in 50-60 DEG C of drying 10-24h, hybrid inorganic-organic dressing is made.Wherein, the wound repair Using referring to that external application of the hybrid inorganic-organic dressing in wound repair control in agent the application of (especially chronic trauma reparation).

Hybrid inorganic-organic dressing of the present invention is by algal polysaccharide sulfate, 3- glycydoxy front three Oxysilane, silica crosslinking obtain, and the hybrid inorganic-organic dressing has wound repairing activity, the organic and inorganic The application of hydridization dressing refer to hybrid inorganic-organic dressing in the clinical treatment of wound repair (especially chronic trauma reparation), The chronic trauma includes burn trauma, foot disease caused by diabetes or chronic refractory conjunction ulcer.

The present invention provides a kind of preparation methods of algal polysaccharide sulfate hybrid inorganic-organic dressing, and it is used Dressing is repaired in wound repair especially chronic wounds, there is biggish specific surface area and pore structure, can be provided natural imitative Raw class extracellular matrix, can promote fibroblastic proliferation, migration, have good suction-operated to inflammatory factor, promote Into the healing of skin wound.Dressing provided by the invention is safe and non-toxic, non-immunogenicity, and good biocompatibility can be very good The refractory conjunction surface of a wound caused by such as diabetes is treated, before having huge application in the treatment of diabetic ulcer wound etc. Scape.Dressing preparation method of the present invention is simple and easy, especially sugared especially suitable for the chronic Hard agglut wound that clinic is widely present Urinate the treatment and nursing of sick ulcer.

Detailed description of the invention

The IR spectrogram of Fig. 1 algal polysaccharide sulfate hybrid inorganic-organic dressing.

Fig. 2 algal polysaccharide sulfate hybrid inorganic-organic dressing scanning electron microscope spectrogram.

Adsorption experiment of Fig. 3 algal polysaccharide sulfate hybrid inorganic-organic dressing to inflammatory factor.

Load and release experiment of Fig. 4 algal polysaccharide sulfate hybrid inorganic-organic dressing to endothelial growth factors.

Specific embodiment

Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the contents of the present invention, those skilled in the art can To make various changes or modifications to the present invention, such equivalent forms equally fall within limited range of the present invention.