CN109966540A - A kind of preparation method and application of nano-chitosan compound calcium alginate medical dressing - Google Patents
A kind of preparation method and application of nano-chitosan compound calcium alginate medical dressing Download PDFInfo
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
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Abstract
The invention discloses a kind of preparation method and applications of nano-chitosan compound calcium alginate medical dressing, are related to biomedical materials field.The method of the present invention are as follows: mix the nano-chitosan aoxidized by TEMPO by different proportion with sodium alginate, calcium carbonate, softener, it stirs evenly, a certain amount of glucolactone is added, several minutes of stirring, pour into mold, static a few hours obtain spongy medical dressing with abundant gel, freeze-drying.Compared with normal gauze, which has the effect of significantly promoting wound healing.This method simple production process, processing is controllable, at low cost, non-toxic, is suitble to large-scale production.It can make bio-medical material, especially there is wide application prospect in fields such as wound repairs.
Description
Technical field
The invention belongs to biomedical materials fields, and in particular to a kind of nano-chitosan compound calcium alginate medical dressing
Preparation method and application.
Background technique
Global annual several hundred million people need to carry out surgical operation, are bound up a wound, are played to wound temporary using medical dressing
Barrier action avoids or controls wound infection to protect human body.Currently, surgical wound is still generally single using the tradition such as gauze
Dressing, but traditional dressing has the disadvantages of antibiotic property is poor and poor to diffusate absorbability, and healing time is slow.With people
The raising of quality of life, surgical patients also correspondingly increase the requirements such as wound healing, comfort level, prefer to shorten rehabilitation duration.
Therefore exploitation is conducive to wound healing and the Medical dressing of rehabilitation also has been to be concerned by more and more people.Generally, newly
Type medical dressing has good gas permeability；Imbibition ability is strong；Certain moisture retention can keep wound moist environment to advantageous
In wound healing；It can hemostasis；With performances such as antibiotic properties.Compared with traditional dressing, Medical dressing can shorten wound and be cured
The time is closed, medical dressing dosage is reduced, significantly shortening nursing time, caters to patient requests.Therefore, there is more high degree of comfort, add
The Medical dressing of fast wound healing and biocompatibility has also welcome the period of expansion of higher speed.
Sodium alginate is a kind of natural polysaccharide extracted from seaweed, has good biocompatibility, biodegradable
Property and excellent hygroscopicity, have no toxic and side effect to human body, are the desirable feedstocks for preparing Medical dressing.It is original with sodium alginate
There are many medical dressing type of material design synthesis, and principal mode includes the forms such as sponge, fiber and gel.But it is single
Sodium alginate medical dressing haves the shortcomings that cell adherence is lower, and the calcium alginate spongioplasm of dry state is crisp and should not bend, and is not easy
Wrapping.
Chitin is a kind of natural polysaccharide with important biomolecule function, is widely present in crustacean, insect and squid
In parietal bone.With excellent cell compatibility, good biocompatibility and biodegradability, immune function can be enhanced, accelerate wound
Mouth healing, analgesic hemostatic.
Therefore, how chitin and sodium alginate are carried out it is compound, make made of dressing have both the advantage of multiple material with
Meet the needs of wound healing, is the problem that the development of Medical dressing is faced.
Summary of the invention
In order to overcome the shortcomings of the prior art, the primary purpose of the present invention is that providing a kind of for burning, scalding
And the preparation method of the nano-chitosan compound calcium alginate medical dressing of the Wound treatings such as wound.TEMPO oxygen will be passed through
Change obtained nano-chitosan to mix with sodium alginate, calcium carbonate, softener by different proportion, stir evenly, is added a certain amount of
Glucolactone stirs several minutes, pours into mold, and static a few hours are obtained spongy medical with abundant gel, freeze-drying
Dressing.This method preparation process is simple, is suitble to large-scale production.
The present invention second is designed to provide the medical dressing that above-mentioned preparation method obtains, which has excellent breathe freely
Property, water imbibition, flexibility, biocompatibility and degradability.Compared with normal gauze, which has significant promotion wound
The effect of healing.
Third of the present invention is designed to provide application of the above-mentioned medical dressing in biomedical materials field.
To achieve the above object, the present invention adopts the following technical scheme:
In a first aspect, providing a kind of preparation method of nano-chitosan compound calcium alginate medical dressing, including walk as follows
It is rapid:
(1) α-chitin or β-chitin are respectively obtained into α-chitin nano whisker, β-chitin by TEMPO oxidation
Nanofiber is configured to aqueous dispersions, and constituent content is 0.05~2.5wt% nano-chitosan, and surplus is water；
(2) calcium carbonate is added in the aqueous dispersions of step (1), is dispersed with stirring, sodium alginate powder is added, makes its concentration
0.5~3wt% is added softener, makes 0~10wt% of its concentration, stirring and dissolving, wherein calcium carbonate quality is sodium alginate
The 5-20% of quality；
(3) fresh glucolactone solution is configured, mixed liquor in step (2) is added to, stirring or vortex 1-2 divide
Clock pours into mold, wherein the amount of the substance of the glucolactone of addition is 2 times of the amount of step (2) carbonic acid calcium substance, quiet
It sets a few hours, porous three-dimensional manometer chitin/calcium alginate sponge can be obtained in primary freeze drying；
(4) sponge cut, encapsulated, Co60Irradiation sterilization is to get nano-chitosan/calcium alginate medical dressing.
Further, α-chitin or β-chitin described in above-mentioned preparation method step (1) are aoxidized by TEMPO and are distinguished
α-chitin nano whisker, β-chitin nano fiber process are obtained, includes:
1g α-chitin or β-chitin are dispersed in 100g distilled water, 2,2,6,6- tetramethyl of 0.016g is sequentially added
Base -1- piperidines aluminium oxide (TEMPO) and 0.1g NaBr, stirring and dissolving are added dropwise 5mmol NaClO solution, and are tieed up with NaOH solution
The pH for holding reaction system is equal to 10, until with a small amount of ethyl alcohol, reaction was completed when NaOH is no longer consumed, is adjusted to neutrality with HCl solution,
Centrifugation 3 times collects precipitating, precipitating is dispersed in water, and ultrasound is up to α-chitin nano whisker or β-chitin nano fiber
Suspension, 4 DEG C save for use.
Preferably, 0.5~1wt% of constituent content of nano-chitosan described in above-mentioned preparation method step (1).
Preferably, softener described in above-mentioned preparation method step (2) is polyethylene glycol or glycerine.
Preferably, the concentration after sodium alginate described in above-mentioned preparation method step (2) is added is 1~2wt%.
Preferably, the mass ratio of nano-chitosan and sodium alginate is 1:10~1:1 in above-mentioned preparation method step (2).
Further, the mass ratio of nano-chitosan and sodium alginate is 1:2~1:4 in above-mentioned preparation method step (2)
Second aspect provides medical dressing made from above-mentioned preparation method.
The third aspect provides application of the above-mentioned medical dressing in biomedical materials field.
The principle of the present invention: chitin whisker or the nanofiber major diameter with higher that chitin TEMPO is aoxidized
Than, large specific surface area, modulus is high, also maintains the intrinsic bioactivity of chitin.A large amount of carboxyls are contained on surface, with sodium alginate
It is easy to carry out compound, obtains three-dimensional porous structure sponge.The addition of chitin can increase cell adhesion, be more advantageous to wound
Healing.
Compared with the prior art, the beneficial effects of the present invention are:
1, basis material (sodium alginate), compound species, compound quantity, the product form of dressing of the present invention are controllable,
Substantially increase its application range.
2, medical dressing prepared by the present invention has excellent gas permeability, flexibility, water imbibition, moisture retention, bio-compatible
Property and biodegradability.Can accelerated cell growth, resist bacterial invasion, prevent wound infection, will not adhesion wound, easily go
It removes, lays a good foundation for further clinical application.
3, preparation method of the present invention is simple, reaction is mild, easy to operate, low energy consumption, environmental-friendly, is suitable for industrial metaplasia
It produces.
4, medical dressing one-pass molding prepared by the present invention, has three-dimensional porous structure, and alternative pure calcium alginate is medical
Dressing, it is contemplated that the invention product future will be used widely in fields such as bio-medical materials, be especially suitable for burn, scald etc.
The treatment of the surface of a wound.
Detailed description of the invention
Fig. 1 is scanning electron microscope (SEM) figure in the section of sponge dressing made from the embodiment of the present invention 1.
Fig. 2 is the cell toxicity test data that sponge is made in the embodiment of the present invention 1,2 and comparison,
MC3T3-E1 cell is selected to carry out experiment detection, blank control is PBS solution.
Fig. 3 is that sponge dressing made from the embodiment of the present invention 1 handles burn injury in rats wound, and the outer of different number of days wound is taken into consideration
Piece and inflammatory factor concentration situation of change,
A is the appearance photo of different number of days wound；B is the statistical chart of different number of days wound area；C inflammatory factor TNFalpha is dense
Degree variation.
Specific embodiment
By following detailed description combination attached drawing it will be further appreciated that the features and advantages of the invention.Provided implementation
Example is only the explanation to the method for the present invention, remaining content without limiting the invention in any way announcement.
Chitin used in following embodiment is derived from cities such as the shell of the crustaceans such as shrimp crab, squid, cuttlefish parietal bones
Common chitin on face.
α-chitin or β-chitin are aoxidized by TEMPO respectively obtains α-chitin nano whisker, β-chitin nanometer
The process of fiber includes:
1g α-chitin or β-chitin are dispersed in 100g distilled water, 2,2,6,6- tetramethyl of 0.016g is sequentially added
Base -1- piperidines aluminium oxide (TEMPO) and 0.1g NaBr, stirring and dissolving are added dropwise 5mmol NaClO solution, and are tieed up with NaOH solution
The pH for holding reaction system is equal to 10, until with a small amount of ethyl alcohol, reaction was completed when NaOH is no longer consumed, is adjusted to neutrality with HCl solution,
Centrifugation 3 times collects precipitating, precipitating is dispersed in water, and ultrasound is up to α-chitin nano whisker or β-chitin nano fiber
Suspension, 4 DEG C save for use.
[embodiment 1]
10g 0.5wt% β-chitin nano fiber is taken, 0.0182g calcium carbonate is added, is dispersed with stirring；0.2g seaweed is added
Sour sodium powder end and 0.05g glycerine, stirring and dissolving；0.0647g glucolactone is added, stirs 2 minutes, pours into mold.It is quiet
Only 24 hours, freeze-drying；Cutting, encapsulation, Co60Irradiation sterilization obtains the nano-chitosan/calcium alginate Medical coating
Material.
[embodiment 2]
10g 0.5wt% α-chitin nano whisker is taken, 0.0182g calcium carbonate is added, is dispersed with stirring；0.2g seaweed is added
Sour sodium powder end and 0.05g glycerine, stirring and dissolving；0.0647g glucolactone is added, stirs 2 minutes, pours into mold.It is quiet
Only 24 hours, freeze-drying；Cutting, encapsulation, Co60Irradiation sterilization obtains the nano-chitosan/calcium alginate Medical coating
Material.
[embodiment 3]
10g 0.25wt% β-chitin nano fiber is taken, 0.0182g calcium carbonate is added, is dispersed with stirring；The sea 0.2g is added
Alginate powder and 0.025g glycerine, stirring and dissolving；0.0647g glucolactone is added, stirs 2 minutes, pours into mold.
Static 24 hours, freeze-drying；Cutting, encapsulation, Co60Irradiation sterilization obtains the nano-chitosan/calcium alginate Medical coating
Material.
[embodiment 4]
10g 0.05wt% β-chitin nano fiber is taken, 0.0045g calcium carbonate is added, is dispersed with stirring；The sea 0.05g is added
Alginate powder, stirring and dissolving；0.0162g glucolactone is added, stirs 1 minute, pours into mold.Static 6 hours, freezing
It is dry；Cutting, encapsulation, Co60Irradiation sterilization obtains the nano-chitosan/calcium alginate medical dressing.
[embodiment 5]
10g 0.5wt% β-chitin nano fiber is taken, 0.0045g calcium carbonate is added, is dispersed with stirring；The sea 0.05g is added
Alginate powder and 0.0125g glycerine, stirring and dissolving；0.0162g glucolactone is added, stirs 1 minute, pours into mould
Tool.Static 6 hours, freeze-drying；Cutting, encapsulation, Co60It is medical to obtain the nano-chitosan/calcium alginate for irradiation sterilization
Dressing.
[embodiment 6]
10g 0.125wt% β-chitin nano fiber is taken, 0.0091g calcium carbonate is added, is dispersed with stirring；The sea 0.1g is added
Alginate powder and 0.2g polyethylene glycol, stirring and dissolving；0.0324g glucolactone is added, stirs 1 minute, pours into mold.
Static 12 hours, freeze-drying；Cutting, encapsulation, Co60Irradiation sterilization obtains the nano-chitosan/calcium alginate Medical coating
Material.
[embodiment 7]
10g 1wt% α-chitin nano whisker is taken, 0.0091g calcium carbonate is added, is dispersed with stirring；0.1g alginic acid is added
Sodium powder end and 0.5g polyethylene glycol, stirring and dissolving；0.0324g glucolactone is added, stirs 1 minute, pours into mold.It is static
12 hours, freeze-drying；Cutting, encapsulation, Co60Irradiation sterilization obtains the nano-chitosan/calcium alginate medical dressing.
[embodiment 8]
10g 2wt% α-chitin nano whisker is taken, 0.0273g calcium carbonate is added, is dispersed with stirring；0.3g alginic acid is added
Sodium powder end and 1g glycerine, stirring and dissolving；0.0971g glucolactone is added, stirs 2 minutes, pours into mold.Static 24 is small
When, freeze-drying；Cutting, encapsulation, Co60Irradiation sterilization obtains the nano-chitosan/calcium alginate medical dressing.
Comparative example
0.2g sodium alginate powder, 0.0182g calcium carbonate are added in 10g distilled water respectively, stirring and dissolving；It is added
0.0647g glucolactone stirs 2 minutes, pours into mold.Static 24 hours, freeze-drying；Cutting, encapsulation, Co60 irradiation
Disinfection, obtains pure calcium alginate sponge.
Cell toxicity test
Sponge obtained by embodiment 1,2 and comparative example is placed in the PBS solution equipped with MC3T3-E1 cell, is carried out at room temperature
Culture.Fig. 2 is the MTT cell toxicity data of sponge, can be seen that the cell quantity of composite sponge is all higher than pure seaweed by data
Sour calcium sponge shows that nano-chitosan introduces and effectively improves the cell compatibility of sponge, and promote osteoblast growth and
Proliferation.
Wound healing assay
Evaluate the promotion wound healing effect of dressing described in embodiment 1.Using rat full skin wound as model, burn wound
Mouth diameter is 15mm, has studied the time-effect relationship of dressing described in embodiment 1 and control group hospital gauze as wound dressing.Its
In, rat week old: 7~8 weeks；Weight: 250~300g；Male, is randomly divided into 2 groups: gauze group, example 1 group, and every group 5.
As shown in figs.3 a and 3b, the healing that example 1 group can be observed obviously is speeded the representative pictures of agglutination.As a result
Show compared with gauze group, the contraction healing of example 1 group rat wound is obvious to be accelerated.Postoperative 6 days, example 1 group performance
Apparent contraction of wounds phenomenon out.9th day, example 1 group had good wound healing effect, and re-epithelialize covers substantially
The surface of a wound.Example 1 group except epithelium regeneration process faster, more preferably, granulation tissue thickness it is more uniform compared with gauze group, and wound
Agglutination will benefit from a better granulation tissue and be formed.In addition, promote wound healing simultaneously, embodiment 1 have compared with
Good biocompatibility, stimulate inflammatory factor TNFalpha caused by body not compared with gauze have significant change (the 3rd day, P=
0.3054；9th day, P=0.3502) (Fig. 3 C).Result of study shows that novel nano chitin/calcium alginate dressing can pass through
Epithelium regeneration is promoted to promote wound healing.Dressing and gauze described in example 1 group are as dressing, number of days that wound heals completely
Respectively 14 days and 16 days.
Claims (9)
1. a kind of preparation method of nano-chitosan compound calcium alginate medical dressing, which comprises the steps of:
(1) α-chitin or β-chitin are respectively obtained into α-chitin nano whisker, β-chitin nanometer by TEMPO oxidation
Fiber is configured to aqueous dispersions, and constituent content is 0.05~2.5wt% nano-chitosan, and surplus is water；
(2) calcium carbonate is added in the aqueous dispersions of step (1), is dispersed with stirring, sodium alginate powder is added, makes its concentration 0.5
~3wt% is added softener, makes 0~10wt% of its concentration, stirring and dissolving, wherein calcium carbonate quality is sodium alginate quality
5-20%；
(3) fresh glucolactone solution is configured, is added to mixed liquor in step (2), stirring or vortex 1-2 minutes,
Enter mold, wherein the amount of the substance of the glucolactone of addition is 2 times of the amount of step (2) carbonic acid calcium substance, and it is small to stand number
When, porous three-dimensional manometer chitin/calcium alginate sponge can be obtained in primary freeze drying；
(4) sponge cut, encapsulated, Co60Irradiation sterilization is to get nano-chitosan/calcium alginate medical dressing.
2. the preparation method of nano-chitosan compound calcium alginate medical dressing according to claim 1, which is characterized in that
α-chitin described in step (1) or β-chitin are aoxidized by TEMPO respectively obtains α-chitin nano whisker, β-chitin
The process of nanofiber includes:
1g α-chitin or β-chitin are dispersed in 100g distilled water, 0.016g2,2,6,6- tetramethyl -1- are sequentially added
Piperidines aluminium oxide (TEMPO) and 0.1g NaBr, stirring and dissolving are added dropwise 5mmol NaClO solution, and remain anti-with NaOH solution
It answers the pH of system to be equal to 10, until reaction was completed with a small amount of ethyl alcohol when NaOH is no longer consumed, is adjusted to neutrality with HCl solution, centrifugation 3
It is secondary, precipitating is collected, precipitating is dispersed in water, ultrasound suspends up to α-chitin nano whisker or β-chitin nano fiber
Liquid, 4 DEG C save for use.
3. the preparation method of nano-chitosan compound calcium alginate medical dressing according to claim 1, which is characterized in that
0.5~1wt% of constituent content of nano-chitosan described in step (1).
4. the preparation method of nano-chitosan compound calcium alginate medical dressing according to claim 1, which is characterized in that
Softener described in step (2) is polyethylene glycol or glycerine.
5. the preparation method of nano-chitosan compound calcium alginate medical dressing according to claim 1, which is characterized in that
Concentration after sodium alginate described in step (2) is added is 1~2wt%.
6. the preparation method of nano-chitosan compound calcium alginate medical dressing according to claim 1, which is characterized in that
The mass ratio of nano-chitosan and sodium alginate is 1:10~1:1 in step (2).
7. the preparation method of nano-chitosan compound calcium alginate medical dressing according to claim 6, which is characterized in that
The mass ratio of nano-chitosan and sodium alginate is 1:2~1:4 in step (2).
8. medical dressing made from the described in any item preparation methods of claim 1-7.
9. application of the medical dressing according to any one of claims 8 in biomedical materials field.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112076344A (en) * | 2020-09-25 | 2020-12-15 | 山东朱氏药业集团有限公司 | Degradable hydrogel medical dressing and preparation process thereof |
| CN112442196A (en) * | 2020-11-23 | 2021-03-05 | 武汉大学 | Preparation and application of degradable, biocompatible and high-strength chitin hydrogel |
| EP4159251A4 (en) * | 2020-06-01 | 2024-06-19 | Otsuka Pharmaceutical Factory, Inc. | Adhesion-preventing agent and method for preventing adhesion using same |
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| EP4159251A4 (en) * | 2020-06-01 | 2024-06-19 | Otsuka Pharmaceutical Factory, Inc. | Adhesion-preventing agent and method for preventing adhesion using same |
| CN112076344A (en) * | 2020-09-25 | 2020-12-15 | 山东朱氏药业集团有限公司 | Degradable hydrogel medical dressing and preparation process thereof |
| CN112442196A (en) * | 2020-11-23 | 2021-03-05 | 武汉大学 | Preparation and application of degradable, biocompatible and high-strength chitin hydrogel |
| CN112442196B (en) * | 2020-11-23 | 2022-03-04 | 武汉大学 | Preparation and application of degradable, biocompatible and high-strength chitin hydrogel |
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| CN109966540B (en) | 2020-06-23 |
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