CN104784740A - Moisturizing antibacterial double-layered composite medical dressing and preparation method thereof - Google Patents

Moisturizing antibacterial double-layered composite medical dressing and preparation method thereof Download PDF

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CN104784740A
CN104784740A CN201510179094.8A CN201510179094A CN104784740A CN 104784740 A CN104784740 A CN 104784740A CN 201510179094 A CN201510179094 A CN 201510179094A CN 104784740 A CN104784740 A CN 104784740A
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preparation
sodium alginate
spongy body
dressing
medical dressing
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CN104784740B (en
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韩志超
王趁红
许杉杉
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Institute of Chemistry CAS
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Institute of Chemistry CAS
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Abstract

The invention relates to a moisturizing antibacterial double-layered composite medical dressing and a preparation method thereof. The preparation method comprises the following steps: 1), pre-freezing a sodium alginate aqueous solution to enable the sodium alginate aqueous solution to be formed, and performing freeze drying to obtain a sodium alginate cavernous body I; 2) immersing the sodium alginate cavernous body obtained in the step 1) in a calcium chloride aqueous solution, taking the immersed sodium alginate cavernous body out to be subjected to freeze drying to obtain a calcium alginate cavernous body II; 3) spinning polymer obtaining antibacterial drug onto the calcium alginate cavernous body II through electrospinning to obtain the composite medical dressing. The moisturizing antibacterial double-layered composite medical dressing has excellent properties of two materials. During use, the layer, in direct contact with the skin, of the dressing is a three-dimensional porous transparent cavernous body, is high in water absorption property, water retention property and air permeability, can clean up excess exudate on a wound surface in time, and can make the wound surface to maintain a certain wettability, so that the wound healing is facilitated; the other layer of the dressing is a drug-loaded electrospinning polymer layer, has excellent mechanical and antibacterial properties, and can play a good protective effect on the wound surface during use.

Description

Antibacterial two-layer compound medical dressing of a kind of moisturizing and preparation method thereof
Technical field
The present invention relates to medical dressing field, be specifically related to antibacterial two-layer compound medical dressing of a kind of moisturizing and preparation method thereof.
Background technology
Skin is one of vitals of human body, plays the important function maintaining human internal environment and stablize and stop microorganism to invade.During the skin damage of people, not only can cause the imbalance of the immunologic function of body own, the defence capability resisting extraneous infringement also significantly be reduced simultaneously.For the skin injury caused by exopathogenic factors such as wound, scald and burns, if processed not in time, body will suffer a series of infringement, even threat to life.Medical dressing is the covering for wound surface, can substitute damaged skin and play temporary transient barrier function, avoid or control wound infection, provide the environment being beneficial to wound healing.
Since Gorge doctor D.Winter in 1962 proposes " moist environment healing is theoretical ", novel wet type dressing develops rapidly.Relative to traditional dryness medical dressing, moist dressing can maintain enough wound moisture, maintains the hydras of wound surface, is conducive to improving enzyme preparation to the debridement efficiency of slough, to strengthen in cell natural factor to the repair ability of wound simultaneously, thus accelerating wound healing.Desirable Medical dressing not only needs to possess physical barriers function to protect wound surface; need there is certain clearing function to wound site simultaneously; can suppress and eliminate the antibacterial near wound and microorganism; ensure the air circulation with the external world in wound healing process; reduce or prevent the formation of scar tissue; strengthen skin self-reparing capability, thus accelerating wound healing.
At present, along with socioeconomic development, the mankind significantly improve for the expected value especially comprising medical level with living standard, and social senilization's trend will increase the chance that chronic wounds is formed simultaneously, and these all will improve the demand to high-performance multifunction bio-medical material.
Summary of the invention
The object of the present invention is to provide antibacterial two-layer compound medical dressing of a kind of moisturizing and preparation method thereof.This medical dressing is double-decker, can play moisturizing and bacteriostasis in use procedure simultaneously.
The preparation method of based composite dressing for medical use provided by the present invention, comprises the steps:
1) sodium alginate spongy body is prepared: by the molding of sodium alginate aqueous solution pre-freeze, and lyophilization, obtain sodium alginate spongy body;
2) prepare calcium alginate spongy body: by step 1) in gained sodium alginate spongy body be immersed in calcium chloride water, take out and lyophilization, obtain calcium alginate spongy body;
3) based composite dressing for medical use is prepared: will containing the polymer solution spinning of antibacterial medicines to step 2 by electrostatic spinning) on middle gained calcium alginate spongy body, obtain based composite dressing for medical use.
In above-mentioned preparation method, step 1) in, the mass fraction of described sodium alginate aqueous solution is 0.5 ~ 5%.
The temperature of described pre-freeze molding is-40 ~-10 DEG C, specifically can be-30 DEG C, and the time is 12 ~ 72h, specifically can be 24h.
Described cryodesiccated temperature is-60 ~-25 DEG C, specifically can be-30 DEG C, and the time is 48 ~ 72h, specifically can be 48h.
Herein, described sodium alginate aqueous solution only need be frozen into fixing bulk by pre-freeze molding, and then through lyophilization, obtains sodium alginate spongy body, and this sodium alginate spongy body, after crosslinked, can carry out size cutting according to the actual needs.
In above-mentioned preparation method, step 2) in, the molar concentration of calcium chloride water is 0.05 ~ 1.0mol/L, specifically can be 0.5 ~ 0.8mol/L.
The time of described submergence is 12 ~ 72h, specifically can be 48h.
Described cryodesiccated temperature is-60 ~-25 DEG C, specifically can be-30 DEG C, and the time is 48 ~ 72h.
Before described lyophilization, also comprise the step that the extract intermediate water of described taking-up is rinsed well.
In above-mentioned preparation method, step 3) in, the compound method of the described polymer solution containing antibacterial medicines is as follows: be first dissolved in organic solvent by polymer and be mixed with the polymer solution of mass volume ratio for (10g ~ 70g): 1000ml, again antibacterial medicines is distributed in described polymer solution, the described polymer solution containing antibacterial medicines can be obtained, wherein, the mass ratio of antibacterial medicines and polymer is (0.1 ~ 15): 100, specifically can be (0.5 ~ 10): 100, the mass volume ratio of polymer and organic solvent specifically can be (15g ~ 45g): 1000ml.
Wherein, described polymer is selected from least one in poly lactic coglycolic acid (PLGA), polycaprolactone (PCL), poly lactic coglycolic acid-glycol copolymer (PLGA-b-PEG), lactic acid-glycol copolymer (PLA-b-PEG) and gelatin.
The weight average molecular weight of described poly lactic coglycolic acid (PLGA) is 50000 ~ 200000, inlay character is LA:GA=(95 ~ 45): (5 ~ 55), is preferably any one in 95:5,90:10,85:15,80:20,75:25,70:30,65:35,60:40 and 45:55.
The weight average molecular weight of described polycaprolactone (PCL) is 50000 ~ 200000.
Described poly lactic coglycolic acid-glycol copolymer (PLGA-b-PEG) is block copolymer, and wherein, the weight average molecular weight of PLGA segment is 50000 ~ 200000, and the weight average molecular weight of PEG chain segment is 1000 ~ 6000.
Described lactic acid-glycol copolymer (PLA-b-PEG) is diblock copolymer, and wherein, the weight average molecular weight of PLA segment is 50000 ~ 200000, and the weight average molecular weight of PEG chain segment is 1000 ~ 6000.
Described organic solvent is selected from least one in DMF, acetone, trifluoroethanol, chloroform, dichloromethane, oxolane and hexafluoroisopropanol.
Described antibacterial medicines is selected from least one in metronidazole, tinidazole, cefoxitin sodium, silver sulfadiazine and nano-Ag particles.
The step of described electrostatic spinning is as follows: the syringe described polymer solution containing antibacterial medicines being injected electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.3 ~ 0.7mm, again described calcium alginate spongy body is fixed on rotating receiver, control voltage is 12 ~ 25kv, solution flow rate is 1 ~ 8mL/h, rotating receiver distance rustless steel syringe needle is under the condition of 10 ~ 25cm, described calcium alginate spongy body carries out electrostatic spinning and obtains based composite dressing for medical use, and at room temperature vacuum drying 24 ~ 48 hours, remove residual solvent, by the regulation and control spinning time, the electrostatic spinning rete of different-thickness can be obtained.
Described electrospinning device is many spinning heads electrostatic spinning machine, and many spinning heads electrostatic spinning machine is herein that this experiment customized.
The antibacterial two-layer compound medical dressing of the preparation-obtained moisturizing of the present invention also belongs to protection scope of the present invention.
For the demand of existing market, the present invention has prepared two-layer compound medical dressing by physical method, and it has had the excellent properties of bi-material concurrently.In use procedure, one deck that itself and skin are directly fitted is three-dimensional porous penetrating spongy body, and this layer has high water suction, high water conservation and air permeability, can clear up the too much transudate of wound surface in time, and the wettability that wound surface can be made to keep certain, be beneficial to wound healing; Another layer is medicine carrying electrostatic spinning polymeric layer, and this layer has good mechanical property and bacteriostasis property, in use can play a very good protection to wound surface.
Beneficial effect of the present invention is as follows:
(1) the antibacterial two-layer compound medical dressing of moisturizing prepared of the present invention, while protection wound surface, also can promote that damaged tissues heals.
(2) it also has high comfort level.Its calcium alginate spongy body has three-dimensional through pore space structure, and its light weight is soft, and use light comfortable, meanwhile, the water absorption high due to it and water-retaining property make excess tissue transudate to remove in time, and keep the wettability of wound surface; Its medicine carrying electrostatic spinning polymeric layer, excellent mechanical property plays a very good protection, and possesses antibacterial sterilization effect simultaneously, and the material that this layer absorbs for biodegradable, still a kind of green material ensureing safely and efficiently while.
(3) preparation method is simple, cost is low, be easy to industrialization produces.While preparing electrostatic spinning functional layer, directly carry out compound by two-layer, avoid more polymictic introducing; The thickness of its double-layer structure can carry out flexible according to actual needs; Having prepared does not have the residual of organic solvent substantially afterwards, does not need special handling just can come into operation.
Detailed description of the invention
Be described method of the present invention below by specific embodiment, but the present invention is not limited thereto, all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.
Experimental technique described in following embodiment, if no special instructions, is conventional method; Described reagent and material, if no special instructions, all can obtain from commercial channels.
Embodiment 1, the antibacterial two-layer compound medical dressing of preparation moisturizing:
1) sodium alginate spongy body is prepared: sodium alginate is soluble in water, be mixed with the sodium alginate soln that concentration is 3% (w/w), pour in diameter 9cm culture dish after stirring at room temperature is even, pre-freeze molding 24h at-30 DEG C, lyophilization 48h at-30 DEG C, obtains sodium alginate spongy body again.
2) prepare calcium alginate spongy body: by step 1) in obtained sodium alginate spongy body to immerse concentration be 48h in the calcium chloride solution of 0.5mol/L, after taking-up, to rinse well with intermediate water, and lyophilization 48h at being placed in-30 DEG C, to obtain final product.
3) prepare electrostatic spinning polymer solution: by weight average molecular weight be 80,000 PLGA (LA:GA=75:25) be dissolved in N, (N in the mixed solvent of dinethylformamide and acetone, dinethylformamide: acetone=5:5, v/v), be mixed with the polymer solution that mass volume ratio is 35g:1000ml, after stirring at room temperature is even, metronidazole is distributed in this polymer solution, stirs.Wherein, metronidazole: PLGA=8:100 (w/w).
4) by step 3) in the mixed liquor that obtains inject the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.5mm, by step 2) in the calcium alginate spongy body that obtains be fixed on dash receiver; Be 15kv at voltage, solution flow rate is 1.5mL/h, and rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 15cm to obtain composite, dry 48 hours of room temperature in vacuo, removes residual solvent.
In preparation moisturizing antibacterial two-layer compound medical dressing process, by step 2) in after the calcium alginate spongy body that obtains is soaked in normal saline 24h, can record its water absorption rate up to 11 times, water retention is 92%; Step 4) in the electrostatic spinning rete that obtains for the 24h bacteriostasis rate of escherichia coli (ATCC 25922) up to 88%.
The infection described medical dressing being carried out miniature pig surgical incision is observed, selected three kinds of materials to do paired observation: a, conventional medical gauze simultaneously, b, by above-mentioned steps 3) and 4) the monolayer static spinning membrane not adding antibacterials prepared, c, the dressing of a kind of commercially available calcium alginate spongy body.Relative to conventional medical gauze and monolayer electrostatic spinning rete, described in commercially available spongy body dressing and this patent, medical dressing can absorb wound extravasating in time and make wound keep moistening degree; Compare other three kinds of contrast materials, the inflammatory reaction of three days is after surgery obviously less to adopt the otch of this medical dressing.Within postoperative two weeks, epidermal structure observed by tissue slice, uses being organized in four groups of process of this medical dressing to have better healing grade, and obviously reduces the formation of scar tissue.
Embodiment 2, the antibacterial two-layer compound medical dressing of preparation moisturizing:
1) sodium alginate spongy body is prepared: sodium alginate is soluble in water, being mixed with concentration is 2% (w/w) sodium alginate soln, pour in diameter 9cm culture dish after stirring at room temperature is even, pre-freeze molding 24h at-30 DEG C, lyophilization 48h at-60 DEG C, obtains sodium alginate spongy body again.
2) prepare calcium alginate spongy body: by step 1) in obtained sodium alginate spongy body to immerse concentration be 48h in the calcium chloride solution of 0.6mol/L, after taking-up, to rinse well with intermediate water, and lyophilization 72h at being placed in-30 DEG C, to obtain final product.
3) prepare electrostatic spinning polymer solution: by weight average molecular weight be 100,000 PCL be dissolved in oxolane, be mixed with the polymer solution that mass volume ratio is 15g:1000ml, after stirring at room temperature is even, tinidazole is distributed in this polymer solution, stirs.Wherein, tinidazole: PCL=10:100 (w/w).
4) by step 3) in the mixed liquor that obtains inject the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.3mm, by step 2) in the calcium alginate spongy body that obtains be fixed on dash receiver; Be 18kv at voltage, solution flow rate is 2mL/h, and rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 15cm to obtain composite, dry 48 hours of room temperature in vacuo, removes residual solvent.
In preparation moisturizing antibacterial two-layer compound medical dressing process, by step 2) in after the calcium alginate spongy body that obtains is soaked in normal saline 24h, can record its water absorption rate up to 10 times, water retention is 90%; Step 4) in the electrostatic spinning rete that obtains for the 24h bacteriostasis rate of escherichia coli (ATCC 25922) up to 90%.
The infection described medical dressing being carried out miniature pig surgical incision is observed, selected three kinds of materials to do paired observation: a, conventional medical gauze simultaneously, b, by above-mentioned steps 3) and 4) the monolayer static spinning membrane not adding antibacterials prepared, c, the dressing of a kind of commercially available calcium alginate spongy body.Relative to conventional medical gauze and monolayer electrostatic spinning rete, described in commercially available spongy body dressing and this patent, medical dressing can absorb wound extravasating in time and make wound keep moistening degree; Compare other three kinds of contrast materials, the inflammatory reaction of three days is after surgery obviously less to adopt the otch of this medical dressing.Within postoperative two weeks, epidermal structure observed by tissue slice, uses being organized in four groups of process of this medical dressing to have better healing grade, and obviously reduces the formation of scar tissue.
Embodiment 3, the antibacterial two-layer compound medical dressing of preparation moisturizing:
1) sodium alginate spongy body is prepared: sodium alginate is soluble in water, being mixed with concentration is 2.5% (w/w) sodium alginate soln, pour in corresponding container after stirring at room temperature is even, pre-freeze molding 24h at-30 DEG C, lyophilization 72h at-25 DEG C, obtains sodium alginate spongy body again.
2) prepare calcium alginate spongy body: by step 1) in obtained sodium alginate spongy body immerse 48h in the calcium chloride solution of concentration 0.8mol/L, after taking-up, to rinse well with intermediate water, and lyophilization 48h at being placed in-30 DEG C, to obtain final product.
3) prepare electrostatic spinning polymer solution: by weight average molecular weight be 200,000 PLGA (LA:GA=75:25) be dissolved in N, (N in the mixed solvent of dinethylformamide and acetone, dinethylformamide: acetone=5:5, v/v), be mixed with the polymer solution that mass volume ratio is 25g:1000ml, after stirring at room temperature is even, nano silver particles diameter being about 40nm is distributed in this polymer solution, stirs.Wherein, nano silver particles: PLGA=0.5:100 (w/w).
4) by step 3) in the mixed liquor that obtains inject the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.6mm, with step 2) in the calcium alginate spongy body that obtains be fixed on dash receiver; Be 12kv at voltage, solution flow rate is 1mL/h, and rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 12cm to obtain composite, dry 48 hours of room temperature in vacuo, removes residual solvent.
In preparation moisturizing antibacterial two-layer compound medical dressing process, by step 2) in after the calcium alginate spongy body that obtains is soaked in normal saline 24h, can record its water absorption rate up to 10 times, water retention is 93%; Step 4) in the electrostatic spinning rete that obtains for the 24h bacteriostasis rate of escherichia coli (ATCC 25922) and staphylococcus aureus (ATCC 25923) all up to 99%.
The infection described medical dressing being carried out miniature pig surgical incision is observed, selected three kinds of materials to do paired observation: a, conventional medical gauze simultaneously, b, by above-mentioned steps 3) and 4) the monolayer static spinning membrane not adding antibacterials prepared, c, the dressing of a kind of commercially available calcium alginate spongy body.Relative to conventional medical gauze and monolayer electrostatic spinning rete, described in commercially available spongy body dressing and this patent, medical dressing can absorb wound extravasating in time and make wound keep moistening degree; Compare other three kinds of contrast materials, the inflammatory reaction of three days is after surgery obviously less to adopt the otch of this medical dressing.Within postoperative two weeks, epidermal structure observed by tissue slice, uses being organized in four groups of process of this medical dressing to have better healing grade, and obviously reduces the formation of scar tissue.
Embodiment 4, the antibacterial two-layer compound medical dressing of preparation moisturizing:
1) sodium alginate spongy body is prepared: sodium alginate is soluble in water, being mixed with concentration is 2.5% (w/w) sodium alginate soln, pour in diameter 9cm culture dish after stirring at room temperature is even, pre-freeze molding 24h at-30 DEG C, lyophilization 48h at-60 DEG C, obtains sodium alginate spongy body again.
2) prepare calcium alginate spongy body: by step 1) in obtained sodium alginate spongy body to immerse concentration be 48h in the calcium chloride solution of 0.5mol/L, after taking-up, to rinse well with intermediate water, and lyophilization 72h at being placed in-30 DEG C, to obtain final product.
3) electrostatic spinning polymer solution is prepared: by PLGA-b-PEG (PLGA weight average molecular weight: 100,000, PEG weight average molecular weight: 5000) be dissolved in hexafluoroisopropanol, be mixed with the polymer solution that mass volume ratio is 15g:1000ml, after stirring at room temperature is even, tinidazole is distributed in this polymer solution, stirs.Wherein, tinidazole: PLGA-b-PEG=10:100 (w/w).
4) by step 3) in the mixed liquor that obtains inject the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.3mm, with step 2) in the calcium alginate spongy body that obtains be fixed on dash receiver; Be 20kv at voltage, solution flow rate is 2mL/h, and rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 12cm to obtain composite, dry 48 hours of room temperature in vacuo, removes residual solvent.
In preparation moisturizing antibacterial two-layer compound medical dressing process, by step 2) in after the calcium alginate spongy body that obtains is soaked in normal saline 24h, can record its water absorption rate up to 12 times, water retention is 92%; Step 4) in the electrostatic spinning rete that obtains for the 24h bacteriostasis rate of escherichia coli (ATCC 25922) up to 88%.
The infection described medical dressing being carried out miniature pig surgical incision is observed, selected three kinds of materials to do paired observation: a, conventional medical gauze simultaneously, b, by above-mentioned steps 3) and 4) the monolayer static spinning membrane not adding antibacterials prepared, c, the dressing of a kind of commercially available calcium alginate spongy body.Relative to conventional medical gauze and monolayer electrostatic spinning rete, described in commercially available spongy body dressing and this patent, medical dressing can absorb wound extravasating in time and make wound keep moistening degree; Compare other three kinds of contrast materials, the inflammatory reaction of three days is after surgery obviously less to adopt the otch of this medical dressing.Within postoperative two weeks, epidermal structure observed by tissue slice, uses being organized in four groups of process of this medical dressing to have better healing grade, and obviously reduces the formation of scar tissue.
Embodiment 5, the antibacterial two-layer compound medical dressing of preparation moisturizing:
1) sodium alginate spongy body is prepared: sodium alginate is soluble in water, being mixed with concentration is 2.5% (w/w) sodium alginate soln, pour in diameter 9cm culture dish after stirring at room temperature is even, pre-freeze molding 24h at-30 DEG C, lyophilization 48h at-30 DEG C, obtains sodium alginate spongy body again.
2) prepare calcium alginate spongy body: by step 1) in obtained sodium alginate spongy body to immerse concentration be 48h in the calcium chloride solution of 0.8mol/L, after taking-up, to rinse well with intermediate water, and lyophilization 48h at being placed in-30 DEG C, to obtain final product.
3) prepare electrostatic spinning polymer solution: by weight average molecular weight be 60,000 PLGA (LA:GA=75:25) and weight average molecular weight be 10,000 PLA-b-PEG (LA:EG=1:1, mol ratio) be dissolved in N, (N in the mixed solvent of dinethylformamide and acetone, dinethylformamide: acetone=5:5, v/v), being mixed with the total mass volume ratio of polymer is the polymer solution of 45g:1000ml, after stirring at room temperature is even, nano silver particles diameter being about 40nm is distributed in this polymer solution, stirs.Wherein, PLGA:PLA-b-PEG=90:10 (w/w); Nano silver particles: total polymer mass=1:100 (w/w).
4) by step 3) in the mixed liquor that obtains inject the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.5mm, with step 2) in the calcium alginate spongy body that obtains be fixed on dash receiver; Be 15kv at voltage, solution flow rate is 3mL/h, and rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 12cm to obtain composite, dry 48 hours of room temperature in vacuo, removes residual solvent.
In preparation moisturizing antibacterial two-layer compound medical dressing process, by step 2) in after the calcium alginate spongy body that obtains is soaked in normal saline 24h, can record its water absorption rate up to 10.5 times, water retention is 90%; Step 4) in the electrostatic spinning rete that obtains for the 24h bacteriostasis rate of escherichia coli (ATCC 25922) and staphylococcus aureus (ATCC 25923) all up to 97%.
The infection described medical dressing being carried out miniature pig surgical incision is observed, selected three kinds of materials to do paired observation: a, conventional medical gauze simultaneously, b, by above-mentioned steps 3) and 4) the monolayer static spinning membrane not adding antibacterials prepared, c, the dressing of a kind of commercially available calcium alginate spongy body.Relative to conventional medical gauze and monolayer electrostatic spinning rete, described in commercially available spongy body dressing and this patent, medical dressing can absorb wound extravasating in time and make wound keep moistening degree; Compare other three kinds of contrast materials, the inflammatory reaction of three days is after surgery obviously less to adopt the otch of this medical dressing.Within postoperative two weeks, epidermal structure observed by tissue slice, uses being organized in four groups of process of this medical dressing to have better healing grade, and obviously reduces the formation of scar tissue.
Embodiment 6, the antibacterial two-layer compound medical dressing of preparation moisturizing:
1) sodium alginate spongy body is prepared: sodium alginate is soluble in water, being mixed with concentration is 2.5% (w/w) sodium alginate soln, pour in diameter 9cm culture dish after stirring at room temperature is even, pre-freeze molding 24h at-30 DEG C, lyophilization 48h at-30 DEG C, obtains sodium alginate spongy body again.
2) prepare calcium alginate spongy body: by step 1) in obtained sodium alginate spongy body to immerse concentration be 48h in the calcium chloride solution of 0.5mol/L, after taking-up, to rinse well with intermediate water, and lyophilization 48h at being placed in-30 DEG C, to obtain final product.
3) prepare electrostatic spinning polymer solution: by weight average molecular weight be 100,000 PLGA (LA:GA=75:25) and weight average molecular weight be 1.5 ten thousand PLA-b-PEG (LA:EG=2:1, mol ratio) be dissolved in hexafluoroisopropanol, being mixed with the total mass volume ratio of polymer is the polymer solution of 18g:1000ml, after stirring at room temperature is even, metronidazole is distributed in this polymer solution, stirs.Wherein, PLGA:PLA-b-PEG=95:5 (w/w); Metronidazole: total polymer mass=1:100 (w/w).
4) by step 3) in the mixed liquor that obtains inject the syringe of electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.4mm, with step 2) in the calcium alginate spongy body that obtains be fixed on dash receiver; Be 20kv at voltage, solution flow rate is 2mL/h, and rotating receiver distance rustless steel syringe needle is carry out electrostatic spinning under the condition of 15cm to obtain composite, dry 48 hours of room temperature in vacuo, removes residual solvent.
In preparation moisturizing antibacterial two-layer compound medical dressing process, by step 2) in after the calcium alginate spongy body that obtains is soaked in normal saline 24h, can record its water absorption rate up to 10 times, water retention is 94%; Step 4) in the electrostatic spinning rete that obtains for the 24h bacteriostasis rate of escherichia coli (ATCC 25922) up to 87%.
The infection described medical dressing being carried out miniature pig surgical incision is observed, selected three kinds of materials to do paired observation: a, conventional medical gauze simultaneously, b, by above-mentioned steps 3) and 4) the monolayer static spinning membrane not adding antibacterials prepared, c, the dressing of a kind of commercially available calcium alginate spongy body.Relative to conventional medical gauze and monolayer electrostatic spinning rete, described in commercially available spongy body dressing and this patent, medical dressing can absorb wound extravasating in time and make wound keep moistening degree; Compare other three kinds of contrast materials, the inflammatory reaction of three days is after surgery obviously less to adopt the otch of this medical dressing.Within postoperative two weeks, epidermal structure observed by tissue slice, uses being organized in four groups of process of this medical dressing to have better healing grade, and obviously reduces the formation of scar tissue.

Claims (8)

1. a preparation method for based composite dressing for medical use, comprises the steps:
1) sodium alginate spongy body is prepared: by the molding of sodium alginate aqueous solution pre-freeze, and lyophilization, obtain sodium alginate spongy body;
2) prepare calcium alginate spongy body: by step 1) in gained sodium alginate spongy body be immersed in calcium chloride water, take out and lyophilization, obtain calcium alginate spongy body;
3) based composite dressing for medical use is prepared: will containing the polymer solution spinning of antibacterial medicines to step 2 by electrostatic spinning) on middle gained calcium alginate spongy body, obtain based composite dressing for medical use.
2. preparation method according to claim 1, is characterized in that: step 1) in, the mass fraction of described sodium alginate aqueous solution is 0.5 ~ 5%;
The temperature of described pre-freeze molding is-40 ~-10 DEG C, and the time is 12 ~ 72h;
Described cryodesiccated temperature is-60 ~-25 DEG C, and the time is 48 ~ 72h.
3. preparation method according to claim 1 and 2, is characterized in that: step 2) in, the molar concentration of calcium chloride water is 0.05 ~ 1.0mol/L;
The time of described submergence is 12 ~ 72h;
Described cryodesiccated temperature is-60 ~-25 DEG C, and the time is 48 ~ 72h;
Before described lyophilization, also comprise the step that the extract intermediate water of described taking-up is rinsed well.
4. the preparation method according to any one of claim 1-3, it is characterized in that: step 3) in, the compound method of the described polymer solution containing antibacterial medicines is as follows: be first dissolved in organic solvent by polymer and be mixed with the polymer solution of mass volume ratio for (10g ~ 70g): 1000ml, antibacterial medicines is distributed in described polymer solution again, namely obtains the described polymer solution containing antibacterial medicines;
Described polymer is selected from least one in poly lactic coglycolic acid, polycaprolactone, poly lactic coglycolic acid-glycol copolymer, lactic acid-glycol copolymer and gelatin;
Described organic solvent is selected from least one in DMF, acetone, trifluoroethanol, chloroform, dichloromethane, oxolane and hexafluoroisopropanol;
Described antibacterial medicines is selected from least one in metronidazole, tinidazole, cefoxitin sodium, silver sulfadiazine and nano-Ag particles;
The mass ratio of described antibacterial medicines and described polymer is (0.1 ~ 15): 100.
5. preparation method according to claim 4, is characterized in that: the weight average molecular weight of described poly lactic coglycolic acid is 50000 ~ 200000, and inlay character is LA:GA=(95 ~ 45): (5 ~ 55);
The weight average molecular weight of described polycaprolactone is 50000 ~ 200000;
In described poly lactic coglycolic acid-glycol copolymer, the weight average molecular weight of poly lactic coglycolic acid segment is 50000 ~ 200000, and the weight average molecular weight of ethylene glycol segment is 1000 ~ 6000;
In described lactic acid-glycol copolymer, the weight average molecular weight of lactic acid segment is 50000 ~ 200000, and the weight average molecular weight of ethylene glycol segment is 1000 ~ 6000.
6. the preparation method according to any one of claim 1-5, it is characterized in that: step 3) in, the step of described electrostatic spinning is as follows: the syringe described polymer solution containing antibacterial medicines being injected electrospinning device, add that in the front end of syringe diameter is the rustless steel syringe needle of 0.3 ~ 0.7mm, again described calcium alginate spongy body is fixed on dash receiver, control voltage is 12 ~ 25kv, solution flow rate is 1 ~ 8mL/h, rotating receiver distance rustless steel syringe needle is under the condition of 10 ~ 25cm, described calcium alginate spongy body carries out electrostatic spinning and obtains described based composite dressing for medical use.
7. the preparation method according to any one of claim 1-6, is characterized in that: step 3) in, also comprise the described based composite dressing for medical use at room temperature vacuum drying step of 24 ~ 48 hours.
8. the preparation method according to any one of claim 1-7 and the based composite dressing for medical use obtained.
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CN115869453A (en) * 2021-09-26 2023-03-31 中国科学院理化技术研究所 Double-layer antibacterial dressing loaded with antibacterial molecules, preparation and application
CN115154642A (en) * 2022-07-05 2022-10-11 福州大学 Bionic asymmetric sponge dressing and preparation method thereof
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CN115487337A (en) * 2022-09-23 2022-12-20 奥精医疗科技股份有限公司 Dressing patch for skin repair and preparation method thereof
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