CN101982202B - Medical hydrogel dressings and preparation method thereof - Google Patents

Abstract

The invention relates to a medical hydrogel dressing and a preparation method thereof. The hydrogel uses 10-30% starch and 2-15% water-soluble polymer as raw materials, and uses guanidinium salt condensation polymer as an antibacterial agent , adding a cross-linking agent and reacting at 40-80°C. The operation steps are to add starch and water-soluble polymers to the solvent to make a solution, adjust the pH value with NaOH solution, then heat up to gelatinize and cool down, and add antibacterial agents and a cross-linking agent, stirred to form a mixed solution, poured into a mold, and reacted at 40-80°C to obtain an antibacterial hydrogel. Compared with the prior art, the hydrogel dressing obtained by the present invention has good swelling performance, high transparency, and moderate mechanical strength, and has an excellent function of resisting bacterial invasion, can effectively prevent wound infection, and has a wide range of raw materials and low prices. Good compatibility and good medical application prospect.

Description

A kind of medical hydrogel dressings and preparation method thereof

Technical field

The present invention relates to dressing of a kind of burn, scald and traumatic wounds use and preparation method thereof, especially relate to a kind of medical hydrogel dressings and preparation method thereof.

Background technology

Skin is the barrier of keeping homoiostasis and stoping the microorganism invasion.Owing to reasons such as wound, scratch, burn and skin ulcerations, may cause the injury on a large scale of skin.It is people's general knowledge that wound easily infects, and this is owing to the pathogen such as staphylococcus aureus, candidiasis and escherichia coli easily cause in the wound breeding.The wound that infects is difficult for healing, easily causes the body fluid loss and causes various complication.Though traditional dressing has protective effect to wound surface; but do not think that generally it has facilitation to wound healing; the damage granulation tissue then postpones wound healing on the contrary during such as change dressings more, and the bacterial resistance that the topical application antibiotic causes in the gauze dressing more makes infective wound surface be difficult to healing.

Doctor Winter of London University in 1962 has invented " wet method therapy ", he finds in zoopery, to be exposed to the air drying wound surface fast again for the speed of wound healing ratio under airtight moist environment, thereby established the theoretical basis that adopts the processing wound surface of new pattern compress.Now prove, use moisture-preserving dressing wound re-epithelialization ability to be significantly improved to the local wet condition of creating an imitation wound surface blister physiological healing of wound, wound surface is healed at faster speed.Therefore, aerogel dressing arises at the historic moment.

Hydrogel is can swelling in water and keep again undissolvable cross linked polymer of large quantity of moisture.Hydrogel has good biocompatibility, is widely used in the multiple fields such as food, medicine.One of important use of medical aquogel is that such dressing water content reaches 96%, can keep the moist environment of wound surface as wound dressing; Repeatedly hydration, the exudate of continuous absorption wound can occur when contacting with tissue; Hydrogel thermal capacity is large, therefore gentle cooling effect is arranged, can significantly reduce pain and the inflammation of postoperative; The translucent healing state of observing wound that is beneficial to.But such dressing is not strong to the buffer action of antibacterial, and the alternative gram-negative bacteria that allows is grown; Easily polluting needs duty to change dressings.

The main preparation methods of hydrogel has chemical method, radiation method and freeze-thaw method etc.Chemical method prepares to be needed in the hydrogel process to add a small amount of cross-linking agent, is to prepare hydrogel method the most commonly used, and the hydrogel character of generation is subjected to the impact of cross-linking monomer, cross-linking agent and reaction condition.Radiation method causes the crosslinked hydrogel that makes by high-energy radiation, and its process need not added chemical cross-linking agent and initiator etc., and product is pure; Radiation can at room temperature be carried out, and reaction condition is gentle, and can be by control properties of product such as control radiation dose; Gel formation can carry out simultaneously with sterilization simultaneously.But mechanical strength is less generally speaking for the hydrogel of radiation method preparation, and is very high to equipment requirements, need electron linear accelerator or ⁶⁰The Co therapy apparatus is restricted its extensive use.Freeze-thaw method is a kind of very effective method for preparing polyvinyl alcohol (PVA) hydrogel of being reported the earliest by Peppas.The hydrogel that the method makes has the advantages such as good springiness and mechanical strength be large, but this hydrogel is a kind of physical gel, can be dissolved into solution when higher temperature; And the swellbility of hydrogel is less and opaque, affects in the therapeutic process observation to wound.The freezing thawing time of reporting in the document is 8～24h usually, and manufacturing cycle is long, is unfavorable for the production of product.

Synthetic high polymer and natural polymer are the materials of present modal preparation hydrogel.Natural polymer because have better biocompatibility and Biodegradable, can not cause rejection or cause wound infection, to the sensitivity of environment and abundant source, cheap price, be subject to widely attention.

In existing patent documentation about aerogel dressing, Chinese patent CN 1225370 has introduced a kind of method for radio-grafting of medical high molecular aquagel membrane.This kind aquagel membrane is take polyethylene glycol oxide, polyvinyl alcohol, water as raw material, and through mold, cold cycling treatment, the processing steps such as RADIATION PROCESSING are made aquagel membrane.Though this kind aquagel membrane has possessed the ability that absorbs and keep the wound exudate, but the water holding capacity of hydrogel is limited, also do not have in the hydrogel can the local antibacterials of using, and increased wound the danger that infects occurs, and have also increased the workload that medical personnel frequently change dressings.

Patent CN 2383500 provides a kind of hydrogel compounded dressing for wound, wet, permeability that this aquagel membrane has, but do not have in the gel to suppress or the composition of kill bacteria, do not possess antibacterial ability initiatively, be easy to cause traumatic infection.

Patent CN 1579559A discloses polyvinyl alcohol hydrogel wound dressing of a kind of pastille, chitosan and preparation method thereof.Contain chitosan in its prescription, but chitosan is water insoluble, and is dissolved in dilute acid soln, thus in preparation process, need the acid neutralization, otherwise dressing has stimulation to wound; This aerogel dressing also contains the additives such as wetting agent, plasticizer, and these additives are easy to separate out in the use procedure of dressing, and wound is had certain side effect; Circulating freezing resistance step in its preparation method, the time is longer, and the freezing and thawing time all needs 8～30 hours, affects its production efficiency.

Patent CN 101664563A discloses a kind of preparation method of anti-bacterial hydrogel dressing, with acrylamide, polyethyleneglycol diacrylate cross-linking agent with contain the water-soluble liquid-phase mixing of natural polymer of nanometer Ag, then places under the room temperature ⁶⁰Co source cross-linking radiation gets anti-bacterial hydrogel dressing.Adopting the anti-bacterial hydrogel dressing of the method preparation is a kind of holey dressing with anti-microbial property and hydrating capacity, but that have antibacterial activity in this dressing is Ag ⁺, easy oxidation discoloration and enter human body by wound may cause harmful effect to health, and safety leaves a question open.

It is gel dressing that the Patent Application No.83305770.6 of EUROPEAN PATENT OFFICE discloses by " the Therapeutic Gel Dressing " of Johnson research and development-treatment.This is a kind of polyvinylpyrrolidone gel of the electron beam crosslinking by 1-5 millirad radiation dose; in manufacturing process, in dressing, add different medicaments; SSD (a kind of antibiotic preparation commonly used) for example; this gel is except absorbing the wound transudate; can also killing bacteria, the protection wound.Its shortcoming is that the gel dressing color of the interpolation medicament that makes under electron radiation is mottled, presents Huang, purple, the different colours such as green, brown, and along with gradually variable color of time, can affect like this observation to the wound situation.

United States Patent (USP) United States Patent No.4294241, Miyata and Teruo have invented a kind of collagen dressing for skin.It adopts the decomposition of protein enzyme to process collagen, forms molecular solution, through purification post-treatment flakiness shape Wound dressing.It has good skin-friendliness, can accelerate epithelial renewal, to organizing nonirritant.This series products water absorption rate is not high, therefore comparatively is fit to this class drying property wound of incised wound property.If the wound surface has more transudate or pus and blood then not too applicable.

Patent US 2009/0326496 A1 has invented a kind of transparent aquagel wound dressing, and this dressing comprises the gel formation fabric and strengthens the sheet-like hydrous gel polymer, and this fabric can absorbing wound exudate and can be seen through dressing and observe wound.The gel formation fiber is sodium alginate fiber, viscose rayon, modified cellulose, cellulose, polyester fiber, polypropylene and copolymer thereof, pectin, chitin fiber, hyaluronic acid fiber or other polysaccharide fiber.Hydrogel layer is then chosen from polyurethane adhesive, biopolymer gel, carboxymethyl cellulose gel, hydroxyethyl-cellulose gel, hydroxypropyl emthylcellulose, modified propylene amide and composition thereof.Gel occurs crosslinked by covalent bond or ionic bond.By extruder aquogel polymer is filled on the reinforced fabric, then dressing is pressed into lamellar.In addition, strengthening hydrogel can be by applying or steep water gel monomer in reinforced fabric, monomer is reacted and makes.

In addition, although commercially available aquogel type wound dressing has solved the problems such as absorption transudate, breathability, obstruct antibacterial, waterproof, wound comfort level, but for the intensity that increases hydrogel, the cohesive that strengthens hydrogel and waterproof and breathable notacoria, majority has adopted fabric or non-woven fabrics as enhancement Layer, and taked the complicated technology of MULTILAYER COMPOSITE, resulting product is opaque structure like this, is not easy to observe the wound healing situation.

Summary of the invention

Purpose of the present invention is exactly to provide a kind of healing of wound, medical hydrogel dressings that antibacterial effect is lasting, production cost is lower and preparation method thereof of promoting for the defective that overcomes above-mentioned prior art existence.

Purpose of the present invention can be achieved through the following technical solutions:

A kind of medical hydrogel dressings is characterized in that, this dressing comprises following component and content (wt%):

Starch 10～30;

Water soluble polymer 2～15;

Cross-linking agent 0.5～10;

Antibacterial 0.1～5;

The solvent surplus.

Described starch is corn starch, wheaten starch, potato starch, soluble starch, sweet potato starch or green starch.

Described water soluble polymer is selected from one or more in polyvinyl alcohol, polyvinylpyrrolidone, carrageenan, gelatin or the agar.

The degree of polymerization of described polyvinyl alcohol is 1200～10000, and alcoholysis degree is 90～100%.

The molecular weight of described polyvinylpyrrolidone is 300000～1000000.

Described cross-linking agent is selected from one or more in epoxychloropropane, Ethylene glycol diglycidyl ether, glutaraldehyde, allyl glycidyl ether, Glycerin triglycidyl ether or the glycerin triglycidyl ether.

Described antibacterial is the water solublity organic antibacterial agent, is selected from the melt polycondensation thing of butanediamine, hexamethylene diamine, octamethylenediamine, decamethylene diamine or m-xylene diamine and guanidine hydrochloride.

Described solvent is deionized water.

A kind of preparation method of medical hydrogel dressings may further comprise the steps:

(1) get the raw materials ready according to following component and kind degree:

Starch 10～30,

Water soluble polymer 2～15,

Cross-linking agent 0.5～10,

Antibacterial 0.1～5,

The solvent surplus;

(2) the water intaking soluble macromolecular is dissolved in the solvent deionized water, stirs, and makes water-soluble polymer solution, and starch is scattered in the water, makes starch dispersion liquid;

(3) with the water-soluble polymer solution in the step (2) and starch dispersion liquid mix homogeneously, with NaOH solution regulation system pH value to 7～13, then be warming up to 50～100 ℃ and keep 5～30min, be cooled to 30～50 ℃;

(4) by formulation content antibacterial is joined in the reaction system that step (3) obtains, stir;

(5) add cross-linking agent in the solution that obtains to step (4) by formulation content, stir and form mixed solution, pour mixed solution into mould, 40～80 ℃ of lower reaction 2～6h namely get anti-bacterial hydrogel dressing.

Compared with prior art, the present invention has the following advantages:

(1) utilize the hydrogel wound dressing of the inventive method preparation to have higher swellbility, a large amount of absorbing wound exudate and keep the moist environment of wound, can the adhesion wound, the secondary damage that has brought when having reduced more change dressings, reduced medical personnel's workload, and make wound be in a stable moist environment, promote the healing of wound;

(2) utilize the hydrogel wound dressing of the inventive method preparation to have the function of excellent opposing bacterial invasion, can effectively prevent wound infection, be conducive to the healing of wound, and save this step of dressing sterilization, simplify technique, reduced production cost;

(3) antibacterial of the present invention is organic guanidine class antibacterial, and it is based on physical action and the Antibacterial Mechanism of killing microorganisms makes aerogel dressing in use can not bring drug-fast problem;

(4) the organic guanidine class antibacterial molecule that adopts is to be incorporated on the strand of starch gel with the chemical bond formal bond, even decocting in water, solvent pop also difficulty break away from antibacterial functions group, thereby can avoid human body to take in the antibacterial of stripping and cause murder by poisoning, and antibacterial effect is lasting;

(5) utilize the hydrogel wound dressing of the inventive method preparation take natural polymer starch as matrix, raw material sources are extensively cheap, and no cytotoxicity and acute toxicity are to skin nonirritant and sensitization, histocompatibility is good, therefore has good medical application prospect.

The specific embodiment

The present invention is described in detail below in conjunction with specific embodiment.

Below the performance test methods of hydrogel among each embodiment, be summarized as follows:

(1) gel fraction: after the hydrogel drying, take deionized water as solvent, apparatus,Soxhlet's extracting 24h:

Gel dry weight * 100% before gel fraction=(gel dry weight after the front gel dry weight-extracting of extracting)/extracting;

(2) secondary swelling ratio: the dry rear 25 ℃ of lower abilities that absorb deionized water of hydrogel:

Gel dry weight * 100% before secondary swelling ratio %=(gel weighs-the front gel dry weight of suction after the suction balance)/suction;

(3) gel strength: use the Lloyd Material Testing Machine to measure and penetrate the required power of starch gel certain depth, the active force of the probe gel that puts on is defined as gel strength when gel breaks;

(4) anti-microbial property: carry out according to the bacteriostatic experiment method FZ/T01021-92 in the health ministry disinfection technology standard in 1992;

(5) wound healing experiment: laboratory animal adopts male Wistar rat, and point of observation is respectively hinders rear 3,5,10,18 days.Rat back is anaesthetized behind the 24h with 8% sodium sulfide loss of thick fluid hair, then scalds with 80 ℃ of water-baths and causes rat back 10% dark II degree skin scald in 15 seconds, hinders to give the 5mL normal saline by the abdominal cavity.Respectively with the anti-bacterial hydrogel dressing flap coverage of embodiment gained; With the hospital gauze flap coverage, organize as a comparison; Put the calculating Wound healing rate observing time:

Wound healing rate=(original wound surface area-the wound surface area does not heal)/original wound surface area.

Embodiment 1

10g pva powder and 5g agar are scattered in the 70g deionized water, are warming up to 85 ℃ of dissolvings, be cooled to 40 ℃, wherein the degree of polymerization of polyvinyl alcohol is 2400, and alcoholysis degree is 99%; The 10g wheaten starch is scattered in the 10g deionized water, joins in above-mentioned polyvinyl alcohol and the agar solution, stir, with 3wt%NaOH solution regulation system pH value to 9, then be warming up to 95 ℃ and keep 20min, be cooled to 30 ℃; It is that 2% aqueous solution joins in the reaction system that 0.8g polytetramethylene guanidine hydrochloride is mixed with mass concentration, stirs; Add again the 5g epoxychloropropane, stir and form mixed solution, pour mixed solution into mould, place 60 ℃ of lower reaction 3h, get anti-bacterial hydrogel dressing.

Embodiment 2

The 10g polyvinylpyrrolidonepowder powder is scattered in the 50g deionized water, stirring and dissolving, wherein the molecular weight of polyvinylpyrrolidone is 1000000; The 15g potato starch is scattered in the 30g deionized water, joins in the above-mentioned polyvinylpyrrolidonesolution solution, stir, with 2wt%NaOH solution regulation system pH value to 10, then be warming up to 80 ℃ and keep 30min, be cooled to 40 ℃; It is that 5% aqueous solution joins in the reaction system that 1.6g polyhexamethylene guanidine hydrochloride is mixed with mass concentration, stirs; Add again the 4g Ethylene glycol diglycidyl ether, stir and form mixed solution, pour mixed solution into mould, place 75 ℃ of lower reaction 3h, get anti-bacterial hydrogel dressing.

Embodiment 3

5g pva powder and 2g gelatin are scattered in the 20g deionized water, are warming up to 85 ℃ of dissolvings, be cooled to 40 ℃, wherein the degree of polymerization of polyvinyl alcohol is 8000, and alcoholysis degree is 91.5%; The 18g soluble starch is scattered in the 60g deionized water, joins in above-mentioned polyvinyl alcohol and the gelatin solution, stir, with 4wt%NaOH solution regulation system pH value to 11, then be warming up to 85 ℃ and keep 15min, be cooled to 30 ℃; It is that 10% aqueous solution joins in the reaction system that the poly-eight methylene guanidine hydrochlorides of 3.0g are mixed with mass concentration, stirs; Add again the 6g glycerin triglycidyl ether, stir and form mixed solution, pour mixed solution into mould, place 70 ℃ of lower reaction 4h, get anti-bacterial hydrogel dressing.

Embodiment 4

10g polyvinylpyrrolidonepowder powder and 5g carrageenan are scattered in the 65g deionized water, stirring and dissolving, wherein the molecular weight of polyvinylpyrrolidone is 800000; The 10g green starch is scattered in the 15g deionized water, joins in above-mentioned polyvinylpyrrolidone and the carrageenan solutions, stir, with 4wt%NaOH solution regulation system pH value to 11, then be warming up to 85 ℃ and keep 30min, be cooled to 30 ℃; To be mixed with mass concentration be that 5% aqueous solution joins in the reaction system to the xyxylene guanidine hydrochloride between 1.6g is poly-, stirs; Add again 4g Glycerin triglycidyl ether, stir and form mixed solution, pour mixed solution into mould, place 60 ℃ of lower reaction 4h, get anti-bacterial hydrogel dressing.

Embodiment 5

The 2g pva powder is scattered in the 20g deionized water, is warming up to 70 ℃ of dissolvings, be cooled to 40 ℃, wherein the degree of polymerization of polyvinyl alcohol is 1200, and alcoholysis degree is 90%; The 20g corn starch is scattered in the 60g deionized water, joins in the above-mentioned poly-vinyl alcohol solution, stir, with 4wt%NaOH solution regulation system pH value to 7, then be warming up to 50 ℃ and keep 30min, be cooled to again 30 ℃; It is that 2% aqueous solution joins in the reaction system that the mixture of 0.1g butanediamine and hexamethylene diamine is mixed with mass concentration, stirs; Add again the 0.5g epoxychloropropane, stir and form mixed solution, pour mixed solution into mould, place 40 ℃ of lower reaction 6h namely to get anti-bacterial hydrogel dressing.

Embodiment 6

The 10g polyvinylpyrrolidonepowder powder is scattered in the 40g deionized water, stirring and dissolving, wherein the molecular weight of polyvinylpyrrolidone is 300000; The 20g wheaten starch is scattered in the 30g deionized water, joins in the above-mentioned polyvinylpyrrolidonesolution solution, stir, with 4wt%NaOH solution regulation system pH value to 13, then be warming up to 100 ℃ and keep 5min, be cooled to again 50 ℃; To be mixed with mass concentration be that 15% aqueous solution joins in the reaction system to the xyxylene guanidine hydrochloride between 5g is poly-, stirs; The mixture that adds again 10g Ethylene glycol diglycidyl ether and glutaraldehyde stirs and forms mixed solution, pours mixed solution into mould, places 80 ℃ of lower reaction 2h namely to get anti-bacterial hydrogel dressing.The performance of the anti-bacterial hydrogel dressing that embodiment 1～6 obtains is as shown in table 1.

The properties of the aerogel dressing for preparing among each embodiment of table 1

The performance of the wound healing of embodiment 1～6 is as shown in table 2.

Table 2 wound healing experimental result

Claims (6)

1. a medical hydrogel dressings is characterized in that, this dressing comprises following component and content (wt%):

Described antibacterial is the water solublity organic antibacterial agent, is selected from the melt polycondensation thing of butanediamine, hexamethylene diamine, octamethylenediamine, decamethylene diamine or m-xylene diamine and guanidine hydrochloride;

Described starch is corn starch, wheaten starch, potato starch, sweet potato starch or green starch;

Described water soluble polymer is selected from one or more in polyvinyl alcohol, polyvinylpyrrolidone, carrageenan, gelatin or the agar.

2. a kind of medical hydrogel dressings according to claim 1 is characterized in that, the degree of polymerization of described polyvinyl alcohol is 1200～10000, and alcoholysis degree is 90～100%.

3. a kind of medical hydrogel dressings according to claim 1 is characterized in that, the molecular weight of described polyvinylpyrrolidone is 300000～1000000.

4. a kind of medical hydrogel dressings according to claim 1, it is characterized in that, described cross-linking agent is selected from one or more in epoxychloropropane, Ethylene glycol diglycidyl ether, glutaraldehyde, allyl glycidyl ether, Glycerin triglycidyl ether or the glycerin triglycidyl ether.

5. a kind of medical hydrogel dressings according to claim 1 is characterized in that, described solvent is deionized water.

6. the preparation method of a medical hydrogel dressings as claimed in claim 1 may further comprise the steps:

(1) get the raw materials ready according to following component and weight percent content:

(2) the water intaking soluble macromolecular is dissolved in the solvent deionized water, stirs, and makes water-soluble polymer solution, and starch is scattered in the water, makes starch dispersion liquid;

(3) with the water-soluble polymer solution in the step (2) and starch dispersion liquid mix homogeneously, with NaOH solution regulation system pH value to 7～13, then be warming up to 50～100 ° of C and keep 5～30min, be cooled to 30～50 ° of C;

(4) by formulation content antibacterial is joined in the reaction system that step (3) obtains, stir;

(5) add cross-linking agent in the solution that obtains to step (4) by formulation content, stir and form mixed solution, pour mixed solution into mould, react 2～6h under 40～80 ° of C and namely get anti-bacterial hydrogel dressing.