CN103341202B - Chitosan sponge surgical dressing and preparation method thereof - Google Patents
Chitosan sponge surgical dressing and preparation method thereof Download PDFInfo
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- CN103341202B CN103341202B CN201310237008.5A CN201310237008A CN103341202B CN 103341202 B CN103341202 B CN 103341202B CN 201310237008 A CN201310237008 A CN 201310237008A CN 103341202 B CN103341202 B CN 103341202B
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Abstract
The invention discloses a chitosan sponge surgical dressing and a preparation method thereof. The chitosan sponge surgical dressing includes, by mass, 0.1% to 10% of water-soluble chitosan or a salt thereof, 0.001% to 5% of a foaming agent and 0.05% to 8% of a humectant. The chitosan sponge surgical dressing provided by the invention has a good foaming effect, high adsorption capacity, powerful moisture retention, softness and good plasticity and fills a gap in excellent surgical dressings.
Description
Technical field
The present invention relates to the crosslinking technological in tissue engineering bracket material, particularly a kind of chitosan sponge body medical dressing and preparation method thereof.
Background technology
Dressing is a kind of medical material that temporary covering wound uses that is used for, and its topmost function is to control transudate and the protection wound of wound, to avoid the pollution of antibacterial and grit, to provide being beneficial to the environment of wound healing.Select suitable dressing to cover on wound, can assist Bleeding control, protect from infection and absorb secretions, thereby promote wound healing.Now dressing plays protection wound surface, prevents that body fluid and protein run off, prevent the effect that antibacterial intrusion causes inflammation, and proliferative cell is provided support.The wound of skin is clinical common disease, when large defect or short time appear in skin, is difficult in the situation of healing, of crucial importance in the dressing of wound surface coverage.For a comparatively long period of time, using the most general surgical wound dressings is medical absorbent cotton and gauze.It can play certain facilitation to the treatment of wound, but has very large deficiency.For example, when it uses, wound surface granulation tissue causes adhesion to growth in dressing; During releasing, easily cause secondary insult; Due to wound surface hydrops, easily cause that antibacterial infects.Along with the progress in epoch and scientific and technological development, by traditional gauze, progressively developed into the wound dressing of the high-tech constituent content of today, in the nearly more than ten years, there is breakthrough variation in the component of dressing and kind.The clinical research and development of dressing of need to giving have proposed requirements at the higher level, also become the power that carries out new pattern compress exploitation.Therefore, develop a kind of new pattern compress, make it can not only flap coverage, can also help wound healing, prevent bacteria attack, reduce superelevation metabolism and the malnutrition of wound area, alleviate wound pain, accelerating wound, have become scientific research personnel's main direction.Therefore, extremely important to improve its quality and water absorbing properties to the crosslinking Treatment of dressing.The matrix material that is generally used for dressing has two classes: natural macromolecular material and synthesized polymer material.Natural macromolecular material mainly contains collagen, gelatin, chitosan, starch, chondroitin sulfate, alginic acid, cellulose etc.Conventional artificial macromolecular material comprises Polyethylene Glycol (PEG), polyurethane (PU), polyvinylpyrrolidone (PVP) etc.In general, natural polymer has excellent biocompatibility and degradability, and synthetic macromolecule has good physical and mechanical properties, processing characteristics and chemical stability.These material controllabilitys are good, and practicality is high, have advantage and disadvantage separately, therefore as biomaterial, in organizational project and regenerative medicine field, obtained application widely.
Natural polysaccharide molecule (as chitosan, starch, alginic acid etc.) is the ideal material of medical dressing, they have good biocompatibility on the one hand, on its strand, there is on the other hand the multiple active function groups reacting, can by modified methods such as grafting, carry out chemical modification easily, can effectively improve the Performance and quality of material.At present a lot of spongy body dressing, all based on this class material, if avoid using poisonous chemical reagent to be cross-linked, such as adopting bimolecular conjugation reaction cross-linking method, is expected to obtain the polysaccharide spongy body medical dressing of high swelling ratio and good biocompatibility.Chitosan, starch, Sargassum acid are natural biologic material, can in human body, be degraded to the glucosamine of safety non-toxic, also can not cause immunogenic response, thereby have good biocompatibility; Chitosan is the unique positively charged glucosamine of occurring in nature simultaneously, because of its unique physics and chemistry structure, make chitosan substance by and erythrocyte membrane between charge effect coagulation erythrocyte stop blooding, and hemostatic mechanism need not depend on clotting mechanism, so can also mediate solidifying of heparinization patient blood, this has unique effect for hemostasis in surgical operation.Chitosan has good biocompatibility, and bioadhesive and multiple biological activity are nontoxic without immune prototype, can body in plurality of enzymes biodegradation, catabolite is nontoxic and can be absorbed completely by human body, is the ideal carrier of medicament slow release.In addition, chitosan also has performance antibacterial, wound healing.
Chitosan has good biocompatibility with it, and biodegradability is stopped blooding and promotes the features such as wound healing, is just becoming the focus of domestic and international research hemostatic material.There is poor toughness and the inapparent problem of haemostatic effect at present simple chitosan hemostatic material.This can be by with other materials or thereby medicine is compound improves toughness and shorten bleeding stopping period, as closed, wait preparation research > > (the health care equipment of < < new field emergency trauma dressing quietly, 2007,28 (9): 1-3.), reported that chitosan and alginic acid calcium salt composite fibre hemostatic material bleeding stopping period are 127.8+33.6s(family's rabbit back both sides 2cm * 2cm wounds); Application number 200610048015.0, denomination of invention be the average bleeding stopping period of < < disclosed chitosan of new and effective Chinese medicine/chitosan compound hemostatic material > > and Chinese medicine (Radix Notoginseng or the Pseudobulbus Bletillae (Rhizoma Bletillae)) compound hemostatic material be inside 165～177s(Mus thigh portion tremulous pulse apply press hemostasis).In prior art, also have and utilize the biocompatibility of chitosan, hemostatic technical scheme of making medical dressing.In actual applications, chitosan is generally made sponge for hemostasis after crosslinked foaming, as patent CN1071587A discloses, a kind ofly with acetic acid, dissolves chitosan, mixes the production technology that becomes sponge after collagen with formaldehyde crosslinking; Patent CN131021A discloses a kind of with acid dissolving chitosan, and glutaraldehyde cross-linking becomes the dry production technology forming of sponge postlyophilization final vacuum; The production technology that Chinese patent CN 200510024503.3 discloses a kind of " adopt after carboxymethyl chitosan glycerol adding, be cross-linked into sponge postlyophilization with environment-protective ion exchanger ".The product that these techniques are produced has all been used cross-linking agent, and it is residual has certain toxicity to human body, and be not foamed into sponge, can not be applied to hemostasis, suck blood and the purposes such as imbibition.
Yet chitosan can not dissolve in neutral aqueous solution, foam performance is not good enough, and with it, preparing sponge often needs to be dissolved in acid solution, regulates the operations such as pH value, washing in sponge production process again.The solubility limits of chitosan in water its range of application.Carboxymethyl chitosan is as the derivant of chitosan, both the advantage that had retained chitosan, has improved again water solublity greatly, simultaneously owing to having introduced carboxymethyl group, make it possess more biological activitys and more good biocompatibility, in medicine and other fields, have multiple use.Therefore also there is document to disclose the application for chitosan derivatives, as: Chinese patent CN 200510024503 discloses a kind of carboxymerhyl chitosan sponge with water-swelling property, in the technical scheme of this disclosure of the invention, utilize the carboxymethyl chitosan sugar aqueous solution that contains carboxymethyl chitosan, chitosan powder or chitin powder, glycerol plasticizer and environment-protective ion cross-linking agent to prepare sponge, but in this technical scheme, sponge is because foaming is insufficient, hole is few and unstable, easily harden, absorbability is poor, and the embrittlement that easily hardens in using; Application number is that China of 20110136324.4 applies for a patent and discloses a kind of sthptic sponge, and this sponge is by molecular sieve and chitosan is compound obtains, and has utilized the good anthemorrhagic performance of chitosan in technical scheme.But only biocompatibility, the biodegradability from chitosan set about in technique scheme, conscientiously do not consider absorption property and soft plasticity when medical bio bressing is used.
Summary of the invention
The object of the invention is to provide the chitosan sponge body that a kind of foaming effect is good, absorbability is high, moisture retention is strong, soft plasticity is strong medical dressing, to solve the deficiency of medical bio bressing in prior art.
For achieving the above object, technical scheme disclosed by the invention is as follows: a kind of chitosan sponge body medical dressing, comprising: water-soluble chitosan or its salt, foaming agent and three kinds of components of wetting agent, and the content of described three kinds of components is respectively by mass percentage:
Water-soluble chitosan or its salt 0.1%-10%;
Foaming agent 0.001%-5%;
Wetting agent 0.05%-8%.
Preferably, the content of described three kinds of components is respectively by mass percentage:
Water-soluble chitosan or its salt 2%-7%;
Foaming agent 0.1%-2%;
Wetting agent 1%-5%.
Preferably, water-soluble chitosan described in the present invention or its salt are selected from least one in using carboxyl chitosan, carboxymethyl chitosan, chitosan hydrochlorate, chitosan acetate, chitosan glutamate salt.Wherein, in preparation process, take carboxymethyl chitosan as best.It is that raw material is made that traditional medical sponge adopts chitin more, and chitin is owing to existing acetylamino and carboxyl, and intermolecular hydrogen bond is stronger, and poorly water-soluble need add chemical cosolvent while making medical sponge, is unfavorable for that human body is used; In the present invention, adopting the good water-soluble chitosan of dissolubility is that primary raw material is made medical sponge, in manufacturing process, without adding cosolvent, reduces the injury that in medical sponge, residual chemical substance causes human body.
Preferably, described in the present invention, medical foaming agent is selected from least one in tween, poloxamer, span, fatty acid glyceride, Span.Poloxamer described in the present invention is as emulsifying agent and stabilizing agent, with the chitosan emulsifying that mixes, the breast grain producing is few, absorbance is high, emulsifying effectiveness is outstanding, physicochemical property is stable, can tolerate-65 ℃ of freezings and+50 ° of ℃ of high temperature dryings, and be shaped to loose porous, constitutionally stable sponge shape.Span described in the present invention can be used as emulsifying agent, stabilizing agent, dispersant, wetting agent, cosolvent, softening agent, and in the chitosan dissolving, span, as senior emulsifying agent, plays the effect of the chitosan that is uniformly dispersed simultaneously.The stability of span, wettability, soft effect, after standing freezing and high temperature drying, not modification of physicochemical property, is shaped chitosan sponge, and soft porous is stable again simultaneously.Tween described in the present invention, Chinese is polyoxyethylene sorbitan fatty acid ester, soluble in water.Tween has the effect of emulsifying diffusion, solubilising, moistening and stabilizing agent, to human body without injury, there is no zest, in the dissolving of chitosan and sponge molding, play the effects such as softening agent, stabilizing agent, foaming agent, wetting agent, after high low temperature, do not change physicochemical property.Fatty acid glyceride described in the present invention, has emulsifying, lubricating function, and non-stimulated to skin and mucosa, safe and reliable, biodegradation is nontoxic.Span described in the present invention is non-ionic surface active agent, soft additive, emulsifying agent, dispersant, cosolvent.Above-mentioned foaming agent can make sponge foaming porous, through not modification of high-low temperature difference, Stability Analysis of Structures.
Through experimentation of the present invention, showing in above-mentioned foaming agent, is more preferably poloxamer.
Preferably, the wetting agent described in the present invention is selected from least one in glycerol, propylene glycol, Polyethylene Glycol.Glycerol described in the present invention, colourless, transparent odorless, is a kind of Organic substance, can be used as softening agent, lytic agent, wetting agent, desiccant.The moisture absorption of glycerol and performance of keeping humidity, not dry not embrittlement after assurance chitosan sponge is shaped, soft flexible.Polyethylene Glycol described in the present invention, nontoxic non-stimulated, good water solublity, there is the good compatibility with many organic matter components, good lubricant, wetting agent, dispersant, glutinous stick, antistatic additive, solubilizing agent and softening agent, to cold and hot stable, safety and stability very while being heated to 150 ℃.Slightly possesses water absorption simultaneously.Be good adjuvant, make the intercommunication network structure of sponge stable, through cold and hot not modification, the sponge after shaping is loose porous, soft full of elasticity.Propylene glycol described in the present invention, nontoxic, zest is less than glycerol, and solubility property is good, viscosity, good hygroscopicity, intersolubility is good, emulsify well.Can make chitosan sponge loose porous, have more elasticity.
Above-mentioned each component can be made into chitosan sponge body medical dressing through certain proportioning, but finds through long term test, and water-soluble chitosan, foaming agent and three kinds of components of wetting agent can reach preferably product effect by a certain percentage.According to the introduction of each detailed composition of above-mentioned each component, chitosan sponge body medical dressing of the present invention, preferably, comprises the component of following mass percent:
Carboxymethyl chitosan 2%-7%
Poloxamer 1%-2%
Polyethylene Glycol 2%-5%.
Preferably, the chitosan sponge body medical dressing described in the present invention, can comprise the component of following mass percent:
Carboxymethyl chitosan 2%-7%
Tween 1%-2%
Polyethylene Glycol 2%-5%.
The above-mentioned proportioning that a kind of chitosan sponge body medical dressing is provided, the invention also discloses a kind of preparation method of chitosan sponge body medical dressing, it is characterized in that, operating procedure is as follows:
Step 1: prepare solution: after getting appropriate foaming agent and fully soaking, be placed in agitator even with the stirring at low speed of rotating speed 100-180 r/min, then in foaming agent solution, add wetting agent, middling speed with 180-400r/min in agitator stirs, add wherein while stirring water-soluble chitosan or its salt to be uniformly dissolved to it, make again agitator with the high-speed stirred of rotating speed 400-700 r/min, solution foaming is expanded, the solution that must foam;
Step 2: pre-freeze: by the good solution Implanted Silicon sealing rubber die dish of above-mentioned foaming, and be placed in the interior pre-freeze 1h～24h of fast freezing case of-70 ℃～-20 ℃, obtain sponge semi-finished product
;
Step 3: by the sponge semi-finished product in step 2, put in vacuum freeze drier, make described sponge semi-finished product between temperature-20 ℃～+ 50 ℃, vacuum is less than under the condition of 30 handkerchiefs, segmentation distils and is incubated, and distillation and insulation are not less than 10 hours total time.
Described in above-mentioned preparation process 3, segmentation distils and is incubated, and comprises once distillation and insulation, secondary distillation and insulation, three distillations and the insulation carried out successively;
By the sponge semi-finished product in step 2, in temperature, be once distil and be incubated under the condition of-18 ℃～-10 ℃, the 20min-90min that wherein distils, insulation 5h-10h; After once distilling and being incubated, carry out continuously secondary distillation and insulation, temperature when secondary distillation and insulation is between-8 ℃～+ 3 ℃ again, and the 15min-70min that wherein distils, is incubated 1h-3h; In secondary distillation and after being incubated, carry out continuously three distillations and insulation, temperature when three distillations and insulation is between+30 ℃～+ 50 ℃, and the 10min-70min that wherein distils, is incubated 1h-3h; Described segmentation distils and the temperature, the time that are incubated have all preset by the computerized control system of described vacuum freeze drier.In the present invention, by the bubble loss of thick fluid mould to after pre-freeze, carry out distillation and the insulation under different temperatures, make sponge progressively be elevated and be incubated, product is loose porous, and aperture is even, and hole count is intensive, and the fragility of product and toughness are all better.
Chitosan sponge body medical dressing of the present invention mainly refers to bio-sponge.
In above-mentioned preparation method, during preparation, foaming agent, purified water are added in container in proportion, according to dissimilar foaming agent, determine different invading the bubble time, as poloxamer, add in proportion after purified water, soak 1 hour.During preparation, adopt rustless steel agitator should be standby high, in, end 3-5 shelves speed regulator (rotating speed 180-400r/min when rotating speed 100-180r/min, middling speed running during low-speed running, rotating speed 400-700r/min while running up), add foaming agent to stir; After foaming agent dissolves completely, wetting agent will be added in solution, middling speed stir treat 2-3 time even to solution, in solution, add water-soluble chitosan to become expanding foam solution to being uniformly dissolved while stirring, high-speed stirred again, when the volume of expanding foam solution expands to original 2-8 times, by expanding foam solution Implanted Silicon sealing rubber die dish, put into as early as possible fast freezing case, make its quick pre-freeze more than 1 hour; Pre-freeze is steeped after loss of thick fluid mould completely, put it into immediately and in vacuum freeze drier, distil and be incubated, sublimation drying is more than 10 hours.In production process of the present invention, increase the link of the demoulding after pre-freeze, saved significantly the time of sublimation drying, saved the energy, improved productivity ratio; Complete after product depanning, cracky is not cracked; Product is sticking mould dish not, makes depanning speed, raises labour efficiency.
The present invention compared with prior art has following advantage:
First, the preparation of traditional bio-sponge product, the general stainless steel mould dish that uses is prepared sponge, after quick-freezing, be difficult to the demoulding, and the freezing crisp easy fracture of goods ice after the demoulding, dry after because of the poor flexibility of bio-sponge, after pressing, being difficult for resilience resets, be difficult to cut, the time-consuming material that takes, is difficult to accomplish large production.And along with the raising of medical level, some bio-sponge products need to make various moulding according to operation, as hollow cylindrical etc., if utilize the words of stainless steel mould dish cannot process.The controlling technology that uses squeezing to be shaped when preparing bio-sponge in the present invention, utilize sticky glutinous, nontoxic silica gel to be processed into the mould of required product moulding, with compressed air, expanding foam solution is pushed to injection molding if desired, and then freeze forming, take out silica gel mould, due to the not sticky glutinous characteristic of silica gel mould, the easily demoulding of finished product.For the flat bulk product without specific (special) requirements, dissolving can be stirred to the water-soluble chitosan having foamed and directly pour required block structure silica gel mould dish, the freezing rear demoulding into.
Secondly, utilize water-soluble chitosan to be combined with foaming agent and form the more powerful mesh structural porous structure of intercommunication in the present invention, under certain proportioning, product possesses better adsorptivity, and the imbibition ability of product is significantly improved; Utilize properly mixed wetting agent, make product possess better elasticity and flexibility, product sticks wound mouth, and absorbability is lasting, has more comfortableness simultaneously.Adopt the controlled casting process of silica gel mould dish, in product vacuum lyophilization process, more can tolerate the not modification of high temperature drying of ultralow low temperature and Geng Gao, product shaping is good simultaneously, form the stable mesh structural porous structure of intercommunication, when medical care or surface injury are used, docile more, absorbability is stronger; Operation can better parcel and support blood vessels or histoorgan in using, and plasticity is stronger.
Finally, the bio-sponge of the bio-sponge that utilizes the technology of the present invention to prepare being prepared with prior art by test is compared, and finds, bio-sponge tool prepared by the present invention has the following advantages: good stability, put for a long time not easy to change, distortion; Foam performance is good, and product is loose porous, and intercommunication network structure is stable; Have more elasticity, more soft, supportive and the toughness of product are improved; Better physical stability, can tolerate cryotherapy and high temperature drying and not modification forms more stable mesh structural porous structure; Possesses antistatic behaviour.
In a word, the invention has the beneficial effects as follows: chitosan sponge body medical dressing foaming effect of the present invention is good, absorbability is high, moisture retention is strong, soft plasticity is strong.
Accompanying drawing explanation
Fig. 1 (a) compares the electron microscope photo scanning of middle matched group one for the liquid absorbency rate of test example one bio-sponge;
Fig. 1 (b) compares the electron microscope photo scanning of middle matched group two for the liquid absorbency rate of test example one bio-sponge;
Fig. 1 (c) compares the electron microscope photo scanning of middle test group for the liquid absorbency rate of test example one bio-sponge;
Fig. 2 is the cell adhesion of the chitin-sodium alginate spongy body medical dressing of different proportion.
The specific embodiment
Below in conjunction with accompanying drawing, preferred embodiment of the present invention is described in detail, thereby so that advantages and features of the invention can be easier to be it will be appreciated by those skilled in the art that, protection scope of the present invention is made to more explicit defining.
Reagent source used in the following embodiment preparation of the present invention: carboxymethyl chitosan, chitosan acetate, using carboxyl chitosan, poloxamer, tween, Span, Polyethylene Glycol, glycerol, propylene glycol: analytical pure, is purchased from Chinese Medicine group;
Instrument used: rustless steel high speed agitator, scanning electron microscope (INCAX-AC T250).
Embodiment mono-: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 2% carboxymethyl chitosan, 1% poloxamer, 2% Polyethylene Glycol.Its preparation method is: poloxamer is added after purified water, soak 1 hour; Then soaked poloxamer is utilized rustless steel agitator with the stirring at low speed of rotating speed 100 r/min 2 times, then reduce to the stirring at low speed of rotating speed 180 r/min 2 times; After poloxamer dissolves completely, Polyethylene Glycol will be added in solution, with the middling speed of 300r/min stir 3 times even to solution, then in solution, add carboxymethyl chitosan to make expanding foam solution to being uniformly dissolved while stirring, make again rustless steel agitator with the high-speed stirred of 700r/min, when the volume of expanding foam solution expands to original 4-5 times, by expanding foam solution Implanted Silicon sealing rubber die dish, put into as early as possible fast freezing case, make its quick pre-freeze 2 hours; Pre-freeze is steeped after loss of thick fluid mould completely, put it into immediately in vacuum freeze drier, once distil successively and insulation, secondary distillation and insulation, three distillations and insulation; By computerized control system, a sublimation temperature of vacuum freeze drier is preset as to-10 ℃, distillation time 90min, insulation 10h; Secondary sublimation temperature is preset as-8 ℃, distillation time 70min, insulation 1h; Three sublimation temperatures are preset as+and 50 ℃, distillation time 70min, insulation 1h.
Embodiment bis-: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 7% carboxymethyl chitosan, 2% poloxamer, 5% Polyethylene Glycol.Its preparation method is: poloxamer is added after purified water, soak 3 hours; Then utilize rustless steel agitator to stir under the speed of 150 r/min soaked poloxamer; After poloxamer dissolves completely, Polyethylene Glycol will be added in solution
,under the speed of 400 r/min, be stirred to solution even, then in solution, add carboxymethyl chitosan to make expanding foam solution to being uniformly dissolved while stirring, under the speed of 700 r/min, stir again, when the volume of expanding foam solution expands to original 4-5 times, by in expanding foam solution Implanted Silicon sealing rubber die dish, put into as early as possible fast freezing case, make its quick pre-freeze 5 hours; Pre-freeze is steeped after loss of thick fluid mould completely, put it into immediately in vacuum freeze drier, once distil successively and insulation, secondary distillation and insulation, three distillations and insulation; By computerized control system, a sublimation temperature of vacuum freeze drier is preset as to-15 ℃, distillation time 20min, insulation 5h; Secondary sublimation temperature is preset as-5 ℃, distillation time 15min, insulation 2h; Three sublimation temperatures are preset as+and 30 ℃, distillation time 10min, insulation 3h.
Embodiment tri-: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 3.5% carboxymethyl chitosan, 1% poloxamer, 2.5% Polyethylene Glycol.Its preparation method is: poloxamer is added after purified water, soak 3 hours; Then utilize rustless steel agitator to stir under the speed of 180 r/min soaked poloxamer; After poloxamer dissolves completely, Polyethylene Glycol will be added in solution
,under the speed of 300 r/min, be stirred to solution even, then in solution, add carboxymethyl chitosan to make expanding foam solution to being uniformly dissolved while stirring, under the speed of 600 r/min, stir again, when the volume of expanding foam solution expands to original 4-5 times, by in expanding foam solution Implanted Silicon sealing rubber die dish, put into as early as possible fast freezing case, make its quick pre-freeze 15 hours; Pre-freeze is steeped after loss of thick fluid mould completely, put it into immediately in vacuum freeze drier, once distil successively and insulation, secondary distillation and insulation, three distillations and insulation; By computerized control system, a sublimation temperature of vacuum freeze drier is preset as to-18 ℃, distillation time 80min, insulation 8h; Secondary sublimation temperature is preset as-8 ℃, distillation time 50min, insulation 1h; Three sublimation temperatures are preset as+and 40 ℃, distillation time 70min, insulation 2h.
Embodiment tetra-: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 2% carboxymethyl chitosan, 1% tween, 5% Polyethylene Glycol.Its preparation method is: poloxamer is added after purified water, soak 3 hours; Then utilize rustless steel agitator to stir under the speed of 160 r/min soaked tween; After tween dissolves completely, Polyethylene Glycol will be added in solution
,under the speed of 200 r/min, be stirred to solution even, then in solution, add carboxymethyl chitosan to make expanding foam solution to being uniformly dissolved while stirring, under the speed of 700 r/min, stir again, when the volume of expanding foam solution expands to original 4-5 times, by in expanding foam solution Implanted Silicon sealing rubber die dish, put into as early as possible fast freezing case, make its quick pre-freeze 10 hours; Pre-freeze is steeped after loss of thick fluid mould completely, put it into immediately in vacuum freeze drier, once distil successively and insulation, secondary distillation and insulation, three distillations and insulation; By computerized control system, a sublimation temperature of vacuum freeze drier is preset as to-12 ℃, distillation time 50min, insulation 6h; Secondary sublimation temperature is preset as+and 1 ℃, distillation time 60min, insulation 3h; Three sublimation temperatures are preset as+and 45 ℃, distillation time 30min, insulation 2h.
Embodiment five: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 4% chitosan acetate, 2% tween, 8% Polyethylene Glycol.Its preparation method is: poloxamer is added after purified water, soak 3 hours; Then utilize rustless steel agitator to stir under the speed of 170 r/min soaked tween; After tween dissolves completely, Polyethylene Glycol will be added in solution
,under the speed of 300 r/min, be stirred to solution even, then in solution, add chitosan acetate to make expanding foam solution to being uniformly dissolved while stirring, under the speed of 400 r/min, stir again, when the volume of expanding foam solution expands to original 4-5 times, by in expanding foam solution Implanted Silicon sealing rubber die dish, put into as early as possible fast freezing case, make its quick pre-freeze 10 hours; Pre-freeze is steeped after loss of thick fluid mould completely, put it into immediately in vacuum freeze drier, once distil successively and insulation, secondary distillation and insulation, three distillations and insulation; By computerized control system, a sublimation temperature of vacuum freeze drier is preset as to-16 ℃, distillation time 40min, insulation 7h; Secondary sublimation temperature is preset as+and 2 ℃, distillation time 50min, insulation 2h; Three sublimation temperatures are preset as+and 35 ℃, distillation time 50min, insulation 2h.
Embodiment six: a kind of chitosan sponge body medical dressing, it comprises the component of following mass percent: 0.1% water soluble shells is poly-, 0.001% foaming agent, 0.05% wetting agent.Its preparation method reference example one.
Embodiment seven: a kind of chitosan sponge body medical dressing, it comprises the component of following mass percent: 10% water-soluble chitosan, 5% foaming agent, 8% wetting agent.Its preparation method reference example one.
Embodiment eight: a kind of chitosan sponge body medical dressing, it comprises the component of following mass percent: 5% water-soluble chitosan, 3% foaming agent, 4% wetting agent.Its preparation method reference example one.
Embodiment nine: a kind of chitosan sponge body medical dressing, it comprises the component of following mass percent: 8% water-soluble chitosan, 1.5% foaming agent, 6% wetting agent.Its preparation method reference example one.
Embodiment ten: a kind of chitosan sponge body medical dressing, it comprises the component of following mass percent: 7% water-soluble chitosan, 0.1% foaming agent, 1% wetting agent.Its preparation method reference example one.
Embodiment 11: a kind of chitosan sponge body medical dressing, it comprises the component of following mass percent: 2% water-soluble chitosan, 2% foaming agent, 5% wetting agent.Its preparation method reference example one.
Embodiment 12: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 6% chitosan acetate, this dish of 4%, 7% glycerol.Its preparation method reference example one.
Embodiment 13: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 3% using carboxyl chitosan, 1.5% Span, 1% propylene glycol.Its preparation method reference example one.
Embodiment 14: a kind of chitosan sponge body medical dressing, be specially medical sponge, and it comprises the component of following mass percent: 9% chitosan glutamate salt, 4.5% fatty acid glyceride, 3% propylene glycol.Its preparation method reference example one.
Below for adopting the comparative experimental example of product prepared by product prepared by technical scheme disclosed in this invention and prior art:
1 test example one: the liquid absorbency rate of bio-sponge is compared
1.1 test procedures:
Test group: press the medical sponge of above-described embodiment one preparation,
Matched group one: do not add poloxamer, all the other components are constant, still presses the medical sponge of embodiment mono-preparation;
Matched group two: do not add Polyethylene Glycol, all the other components are constant, still presses the medical sponge of embodiment mono-preparation;
Matched group three: according to the medical sponge of embodiment bis-preparations in CN 200510024503.
test method:by the above-mentioned liquid absorption of respectively organizing medical sponge of centrifugal determination.Utilize scanning electron microscope scanning respectively to organize medical sponge structure, accompanying drawing 1 represents that scanning electron microscope amplifies the medical sponge photo of 200 times, and in figure, scale represents 100 μ m.
By the blockage of test group and the about 1cm of each matched group medical bio-sponge clip length of side, nearly weigh 0.028g, put into respectively approximately 25 ℃, the beaker of 2ml purified water are housed, place 5 minutes, then put into centrifuge, under the rotating speed of 500rpm, after centrifugal 10min, take out sample, residual liquid is measured respectively, each sampling test 5 times, calculates the residual liquid meansigma methods that weighs every 0.1g sample.
1.2 result of the tests: the pick up test data of table 1 medical sponge of the present invention
Compare with matched group one:
*p<0.05, has significant difference; Compare with matched group two,
▲p<0.05, has significant difference; Compare with matched group three:
△p<0.05, has significant difference.
From above-mentioned test data, can find out, test group is compared with matched group one, matched group two and matched group three each groups, and the liquid absorbency rate of test group has significant difference.Utilize the pick up of medical sponge of the matched group three that the liquid absorbency rate of medical sponge prepared by the present invention prepared than prior art good, differ maximum multiplying power and reach 2.05 times.Fig. 1 (a) is the electron microscope photo scanning of matched group one, Fig. 1 (b) is the electron microscope photo scanning of matched group two, the electron microscope photo scanning that Fig. 1 (c) is test group, in observation by Fig. 1 (a), Fig. 1 (b) and three groups of electron microscope photo scannings of Fig. 1 (c) and table 1, data analysis can obtain: the network structure of the medical sponge of test group is stable, loose porous, therefore evenly, adsorbance is large in water suction; The network structure of the medical sponge of matched group one, matched group two and matched group three is even not, and pore size is uneven, unstable, therefore absorption is even not, absorbability is slightly poor.
test example two: the stability test of bio-sponge
2.1 test methods:
Test group: press the medical sponge of above-described embodiment two preparations,
Matched group one: do not add Polyethylene Glycol, all the other components are constant, still presses the medical sponge of embodiment bis-preparations;
Matched group two: commercial medical chitosan bio-sponge.
Get respectively and respectively organize medical sponge equivalent, carry out accelerated stability test, study on the stability data are as shown in table 2.
2.1.1 accelerated stability test condition and detecting step:
accelerated test:chitosan bio-sponge dressing (calling sponge in the following text) acceleration environment: 40 ± 1 ℃, humidity: 60% ± 10%RH, investigation time=RT/Q10(40-25)/10=2 * 12/21.5=8.48 month=8 first quarter moons.
detect:device therefor is pHS-25C type acidometer, and during detection, first the phosphate standard buffer solution with pH=6.86 positions, and then with the Potassium Hydrogen Phthalate standard buffer solution of pH=4.00, carries out oblique adjusting rate, finally surveys the pH value of solution to be measured.
loss on drying detects:device therefor is baking oven, and during detection, sample thief is appropriate, at 60 °, is dried to after constant weight, by less loss weight and sampling amount, calculates loss on drying.
steriling test:key instrument: ZW-808A type germ collector, MJ-1608 mold incubator, HH.BII-500-BS electro-heating standing-temperature cultivator, YX280A rustless steel steam autoclave, constant temperature roaster, centrifuge, biological microscope, vacuum shelf, standard P H color comparator, totally-enclosed filtration system etc.
steriling test method:clean environment under 10000 grades, in the way flow air section or shielding system of 100 grades, first prepares culture medium, checks the suitability, sterilizing, the sensitivity of culture medium: prepare diluent, flushing liquor: verification experimental verification method, then judged result.Then steriling test test sample, processes and inoculation medium, then cultivates and observes, last judged result.This test all samples and reference substance, the equal well-grown of positive control pipe, negative control pipe asepsis growth, all test sample pipes are all clarified, asepsis growth.
It is as follows that 2.2 test datas record result:
The stability test data of table 2 bio-sponge
conclusion:
test group:sponge is stored in relative humidity and is no more than 80%, and temperature is-5 ℃～30 ℃, non-corrosiveness gas and draughty indoor, and there is not outward appearance, pH value, loss on drying variation and can keep aseptic condition in product.
matched group 1:sponge is stored in relative humidity and is no more than 80%, and temperature is-5 ℃～30 ℃, non-corrosiveness gas and draughty indoor, and product produces outward appearance in allowed band value, and yellowing phenomenon, loss on drying have phenomenon of losing water in allowed band value a little.PH value does not occur product changes and can keep aseptic condition.
matched group 2:sponge is stored in relative humidity and is no more than 80%, and temperature is-5 ℃～30 ℃, non-corrosiveness gas and draughty indoor, and product produces outward appearance in allowed band value, and yellowing phenomenon, loss on drying have phenomenon of losing water in allowed band value a little.PH value does not occur product changes and can keep aseptic condition.
Contrast learns, the stability of test group medical sponge is better than the stability of the medical sponge of matched group 1 and matched group 2.
test example three: the sticky stickiness test of skin of bio-sponge
3.1 test methods:
Test group: the biological sponge of getting the embodiment of the present invention three preparations;
Matched group: get the bio-sponge that commercially available traditional handicraft is manufactured;
Test procedure: respectively get the appropriate also noting marker of test group and matched group bio-sponge, put into respectively same beaker, use purified water moistening, room temperature was invaded bubble after 24 hours, took out respectively two kinds of samples.Perusal hands touch pinches two kinds of products: test group product becomes evenly cotton-shaped, with hands, touches and pinches without sticky stickiness, and comfortable feel, proves and can contact with wound face evenly, simultaneously not sticky glutinous skin; Matched group product occurs that sponge is cotton-shaped inhomogeneous, is slightly with little microlith, with hands, touches and pinches, and product subsurface has sticky glutinous sticky feeling, illustrate while using, contact evenly not with wound, and easy gluing sticks skin.
test example four: the cell adhesion of bio-sponge detects
4.1 test methods:
Test group: the bio-sponge of getting the embodiment of the present invention three preparations;
Matched group one: get the bio-sponge that commercially available traditional handicraft is manufactured;
Matched group two: do not add Polyethylene Glycol, all the other components are constant, still presses the bio-sponge of embodiment tri-preparations;
Matched group three: do not add poloxamer, all the other components are constant, still presses the bio-sponge of embodiment tri-preparations;
Get above-mentioned each group through the bio-sponge equivalent of 60Coradiation sterilizing, be cut into respectively circle and size and 24 well culture plate (Nunc
tM, Denmark) aperture is consistent, and each group bio-sponge is paved with respectively to each culture plate bottom.On bio-sponge surface, all inoculating quantity is 5 * 10
4human body fibroblast, and all add 3 milliliters of culture fluid (DMEM culture medium+10% calf serum+100 units per ml penicillin/streptomycin), be put at 37 ℃ and hatch after 4 hours and take out, by phosphate buffered solution, repeatedly rinse to remove the cell not adhering to, then the phosphate buffered solution that adds 20 microlitre 0.5wt%MTT, be placed in to hatch at 37 ℃ and after 4 hours, add 200 microlitre dimethyl sulfoxide, after vibration evenly, adopt microplate reader (Biorad, Model 550) in 570 nm places, to measure respectively the absorbance of purple material.Concrete data are participated in accompanying drawing 2, and the superficial cell adhesion value of test group is very low, compares with matched group one, matched group two and matched group three, and the superficial cell adhesiveness of test group, lower than other three groups of matched groups, has significant difference.
Chitosan sponge body medical dressing prepared by the present invention is sponge loose structure, and average pore size is 100 microns of left and right, and mutually runs through, and is conducive to the absorption (Fig. 1 (C)) of ventilative and moisture.Other chitosan sponges in the prior art of comparing, chitosan sponge of the present invention loose porous, hole is not only intensive and hole size is even, pore size is moderate, the water absorbing capacity of chitosan sponge dressing of the present invention is extremely strong, can absorb the liquid (table 1) that is equivalent to 17 ~ 25 times of own wts.The stability of chitosan sponge body medical dressing of the present invention is better, can store that in 8.5 months, outward appearance does not occur product, loss on drying changes and keep aseptic condition (table 2).The sticky stickiness test of skin of chitosan bio-sponge of the present invention shows that product can contact evenly with wound face, and not sticky glutinous skin, and the wounded is without sense of discomfort.Because the cell adhesion of dressing is that sponge design needs a very important problem of considering.The dressing causing because material is incorrect adheres to granulation tissue, thereby causes the secondary damage bringing when dressing removes, and comprises the adhesion to granulation, to the epithelial cell of migration, fibroblastic infringement of hypertrophy, even more serious than not using dressing.The superficial cell adhesion value of the test group in test example four of the present invention is very low, significantly lower than other three groups of matched groups (Fig. 2), hydrophilic that dressing of the present invention is described is high, water absorbing capacity is strong, thereby is unfavorable for the adhesion of cell, and such dressing is unlikely causes tissue adhesion.
The foregoing is only embodiments of the invention; not thereby limit the scope of the claims of the present invention; every equivalent structure or conversion of equivalent flow process that utilizes description of the present invention and accompanying drawing content to do; or be directly or indirectly used in other relevant technical fields, be all in like manner included in scope of patent protection of the present invention.
Claims (1)
1. a preparation method for chitosan sponge body medical dressing, is characterized in that, described chitosan sponge body medical dressing comprises the component of following mass percent:
Carboxymethyl chitosan 2%-7%
Poloxamer 1%-2%
Polyethylene Glycol 2%-5%,
Its preparation method operating procedure is as follows:
Step 1: prepare solution: get appropriate foaming agent poloxamer and fully soak after 1 hour, be placed in agitator even with the stirring at low speed of rotating speed 100-180 r/min, then in foaming agent solution, add wetting agent Polyethylene Glycol, middling speed with 180-400r/min in agitator stirs, add wherein while stirring water-soluble chitosan carboxymethyl chitosan to be uniformly dissolved to it, make again agitator with the high-speed stirred of rotating speed 400-700r/min, solution foaming is expanded, the solution that must foam;
Step 2: pre-freeze: by the good solution Implanted Silicon sealing rubber die dish of above-mentioned foaming, be placed in the interior pre-freeze 1h～24h of fast freezing case of-70 ℃～-20 ℃, obtain sponge semi-finished product;
Step 3: by the sponge semi-finished product in step 2, put in vacuum freeze drier, make described sponge semi-finished product between temperature-20 ℃～+ 50 ℃, vacuum is less than under the condition of 30 handkerchiefs, segmentation distils and is incubated, and distillation and insulation are not less than 10 hours total time;
Described segmentation distils and is incubated, and comprises once distillation and insulation, secondary distillation and insulation, three distillations and the insulation carried out successively;
Particularly, be in temperature, to be once distil and be incubated under the condition of-18 ℃～-10 ℃ by the sponge semi-finished product in step 2, the 20min-90min that wherein distils, insulation 5h-10h; After once distilling and being incubated, carry out continuously secondary distillation and insulation, temperature when secondary distillation and insulation is between-8 ℃～+ 3 ℃ again, and the 15min-70min that wherein distils, is incubated 1h-3h; In secondary distillation and after being incubated, carry out continuously three distillations and insulation, temperature when three distillations and insulation is between+30 ℃～+ 50 ℃, and the 10min-70min that wherein distils, is incubated 1h-3h;
Described segmentation distils and the temperature, the time that are incubated have all preset by the computerized control system of described vacuum freeze drier.
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| CN104189940A (en) * | 2014-08-28 | 2014-12-10 | 青岛美科医疗器械有限公司 | Antibacterial liquid dressing containing chitosan hydrochloride and preparation method thereof |
| CN105194716A (en) * | 2015-10-16 | 2015-12-30 | 柏为（武汉）医疗科技有限公司 | Absorbable hemostatic medical polymer material and preparation method thereof |
| WO2018204565A1 (en) * | 2017-05-03 | 2018-11-08 | Warner Babcock Institute For Green Chemistry, Llc | Cushion |
| CN107722336A (en) * | 2017-10-18 | 2018-02-23 | 德清舒华泡沫座椅有限公司 | The antibacterial sponge and its preparation technology of a kind of environment-friendly degradable |
| CN107652477A (en) * | 2017-10-18 | 2018-02-02 | 德清舒华泡沫座椅有限公司 | A kind of environment-friendly antibacterial sponge and its preparation technology |
| CN112023110B (en) * | 2020-08-06 | 2021-11-19 | 西安交通大学 | Active antibacterial dressing based on bamboo fungus egg extract |
| CN114533937B (en) * | 2022-02-14 | 2023-01-03 | 北京冠合医疗科技有限公司 | Biodegradable temperature-sensitive embolic gel and preparation method and application thereof |
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