CN109096522A - It is a kind of with the medical plural gel of more biological functions, preparation method and applications - Google Patents
It is a kind of with the medical plural gel of more biological functions, preparation method and applications Download PDFInfo
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- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
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- C08J2329/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal, or ketal radical; Hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Derivatives of such polymer
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- C08J2329/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
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Abstract
The invention discloses a kind of with the medical plural gel of more biological functions, preparation method and applications.It is using the degradable hydrogel of crosslinking as substrate, composite medical degradable metal and/or alloying pellet, is designed by the ingredient of gel base and degradable metal particle, makes it have good processability and mechanical property.After being implanted into site of action, plural gel can absorb body fluid after contacting body fluid, and surface and internal degradable metal/alloying pellet react with body fluid and degraded, and discharge Biofunctional ion, gradually forms porous structure, and guidance cambium is grown into；Meanwhile the Biofunctional ion discharged can play anti-infective, anticancer, vascularization, promote the regenerated function of surrounding tissue.Material provided by the invention can greatly improve regeneration effect, while have excellent mechanical performances and rapid shaping, can be used for the fields such as Various Tissues defect repair, infection and treatment of sepsis and treatment of cancer.
Description
Technical field
The present invention relates to a kind of medical plural gel, in particular to a kind of medical plural gel with more biological functions,
Preparation method and applications are related to biomaterial, medical instrument, 3D printing, organizational project, pharmaceutical sanitary field.
Background technique
Gelatin, collagen, alginic acid, polyvinyl alcohol, polyethylene glycol, starch, cellulose, chitosan, hyaluronic acid, sulfuric acid are soft
The macromoleculars gel rubber material such as ossein have excellent hydrophily, biocompatibility, degradability and adjustable mechanical property, by
It is widely used in the pharmaceutical sanitary fields such as organizational project, drug release, medical instrument.But currently, the gel rubber material of more biological functions,
The gel rubber material for being such as provided simultaneously with rush regeneration, vascularization and anti-infection property energy still lacks.
Existing research proves the bioactivity that suitable porous structure can greatly improve hydrogel material and guidance tissue again
Raw ability.The prior art mostly prepares porous aquagel using preforming method, asks there are initial mechanical intensity is lower
Topic, more important is implantation process may destroy its porous structure, influences its biology effect.
In recent years, Biofunctional element obtains going deep into announcement for adjusting the effect of biologically.As magnesium, strontium, silicon,
Calcium can promote bone tissue regeneration；Magnesium, silicon, copper can promote vascular tissue's regeneration；Magnesium, copper, zinc, silver have antibacterial or bactericidal effect；
Selenium has antitumaous effect.
Therefore, constructing one kind based on macromolecular gel rubber material being capable of in-situ preparation porous structure and a variety of biology of controlled release
The Wholly-degradable material of functional elements is, it can be achieved that a variety of biological functions, are expected to be widely applied in medicine and hygiene fields, especially
Situ treatment suitable for Regeneration and Repair and certain diseases after Various Tissues damage.
Summary of the invention
The present invention in view of the deficienciess of the prior art, provide it is a kind of have good moulding ability, mechanical property, can be complete
Degradable and in-situ preparation porous structure, while the energy a variety of Biofunctional elements of controlled release, to realize a variety of biological function
The medical plural gel of energy, preparation method and applications.
Realize that the technical solution of the object of the invention is to provide a kind of medical plural gel with more biological functions, it is to hand over
Biodegradable macromolecular gel after connection is continuous substrate phase, accounts for biodegradable metal/conjunction of mass percent 5~50%
Gold particle is uniformly distributed in continuous substrate phase；The biodegradable macromolecular gel include gelatin, collagen, alginic acid,
Polyvinyl alcohol, polyethylene glycol, starch, cellulose, chitosan, hyaluronic acid, chondroitin sulfate；The biodegradable gold
Category/alloying pellet partial size is 10~1000 μm, including pure zinc, kirsite, pure magnesium, magnesium alloy；The medical plural gel
Water absorption >=1 times own wt, water suction balance after compressive strength be 0.1~1000kPa, fracture elongation be 30~
1000%。
Technical solution of the present invention further includes two kinds that preparation has the medical plural gel of more biological functions as described above
Method, one such preparation method include the following steps:
(1) by mass percentage 1~50%, biodegradable macromolecular gel is add to deionized water, heating, stirring bar
Gel solution is obtained under part, obtains thick liquid after cooling；The biodegradable macromolecular gel includes gelatin, glue
Original, alginic acid, polyvinyl alcohol, polyethylene glycol, starch, cellulose, chitosan, hyaluronic acid, chondroitin sulfate；
(2) by mass percentage 0.05~50%, degradable metal/alloying pellet is added to the thick liquid that step (1) obtains
In, the partial size of the biodegradable metal/alloy particle is 10~1000 μm, including pure zinc, kirsite, pure magnesium, magnesium close
Gold；Through being thoroughly mixed, stands under conditions of temperature is 0~20 DEG C, had after the abundant self-crosslinking of gel and after drying
There is the medical plural gel of more biological functions, or self-crosslinking obtained plural gel is placed in cross-linking agent solution to carry out secondary friendship
Connection, the crosslinking agent includes glutaraldehyde, formaldehyde, Geniposide, square diethyl phthalate, glyoxal, oxalic acid, β-phosphoglycerol, water-soluble
Property carbodiimide, or contain calcium ion, zinc ion, magnesium ion, ferrous ion, strontium ion, tripolyphosphate radical ion, sulfate radical
The aqueous solution of ion, citrate ion one of which；Again after deionized water is sufficiently cleaned and dried, obtain that there are more biological function
The medical plural gel of energy.
There is the method for the medical plural gel of more biological functions to include for another preparation that technical solution of the present invention provides
Following steps:
(1) by mass percentage 1~50%, biodegradable macromolecular gel is add to deionized water, heating, stirring bar
Gel solution is obtained under part, obtains thick liquid after cooling；The biodegradable macromolecular gel includes gelatin, glue
Original, alginic acid, polyvinyl alcohol, polyethylene glycol, starch, cellulose, chitosan, hyaluronic acid, chondroitin sulfate；
(2) in the case where temperature is 0~50 DEG C of stirring condition, by mass percentage 0.1~50%, by degradable metal/alloying pellet
It is added in the thick liquid that step (1) obtains, crosslinking agent is added after being sufficiently mixed, then under conditions of temperature is 0~10 DEG C
6~24 hours are stood, the plural gel after being crosslinked；The partial size of the biodegradable metal/alloy particle be 10~
1000 μm, including pure zinc, kirsite, pure magnesium, magnesium alloy；The crosslinking agent includes glutaraldehyde, formaldehyde, Geniposide, side's acid two
Ethyl ester, glyoxal, oxalic acid, β-phosphoglycerol, water-soluble carbodiimide, or contain calcium ion, zinc ion, magnesium ion, ferrous iron
Ion, strontium ion, tripolyphosphate radical ion, sulfate ion, citrate ion one of which aqueous solution；
(3) plural gel that step (2) obtains sufficiently is cleaned and dried with deionized water, or that plural gel is placed in crosslinking agent is molten
It is sufficiently cleaned and dried with deionized water again after carrying out secondary cross-linking in liquid, obtains the medical plural gel with more biological functions.
The application of medical plural gel provided by the invention with more biological functions, can be used for tissue engineering bracket
Material, 3D printing material, dressing, as Implantable Medical Device for Repair of tissue defect, infection and sepsis, the office of tumour
Portion's treatment.
In technical solution of the present invention, the starch includes corn, potato, wheat, sweet potato, sweet potato, cassava, glutinous rice original
Starch and its modified starch.
The pure zinc, Zn-ef ficiency mass fraction > 99%；The kirsite, wherein being 1 containing mass fraction summation
~50% alloying element, including copper, magnesium, silver, manganese, selenium, strontium, calcium, iron, zirconium, silicon；The pure magnesium, magnesium elements mass fraction
> 99%；The magnesium alloy, wherein containing mass fraction summation be 1~50% alloying element, including zinc, copper, silver, manganese, selenium,
Strontium, calcium, iron, zirconium, silicon.
The mechanism of action of plural gel provided by the invention is: using macromolecular hydrophilic gel as substrate phase, having excellent
Biocompatibility and good moulding ability；Degradable metal has a variety of biologies by degradation controlled release functional ion
Function and bacteria resistance function further utilize the Biofunctionals alloying elements such as alloyage process addition strontium, copper, silver, silicon, calcium, selenium
Into metallic particles, can controllable sustained-release several functions ion in vivo, assign anti-infective material, antibacterial, vascularization, promote week
Enclose a variety of biological functions such as regeneration.Importantly, implantation after gel by absorb body fluid be formed by uniqueness inside water ring
Border makes the degradable metal of material internal that can degrade prior to hydrogel matrix, on the one hand passes through particle in-situ degradation and production in situ
Effectively in-situ preparation three-dimensional level porous structure guidance tissue and blood vessel are grown into angry body two ways, on the other hand can be given birth to
At above-mentioned functional ion and by hydrogel network slow release in surrounding tissue, a variety of Biofunctionals are played.
Plural gel provided by the invention have a characteristic that 1. have good moulding ability, after implantation with surrounding group
It knits to be formed and fit closely；2. after implantation, material can continue controllably slow-release function ion, promote surrounding tissue and blood vessel again
It is raw, and the functions such as anti-infective, anticancer are played, carry out injury in treating in situ；3. function, material effectively shape in situ
At three-dimensional level porous structure and new tissue and blood vessel is guided to grow into, while lasting promoting to grow into material inside organization and blood vessel
Growth, final degradable absorption, is substituted, catabolite is nontoxic by cambium.Therefore, this plural gel can play damage and control
Treat the double action with guide tissue regeneration.More importantly the ingredient and performance of gel and degradable metal can be in wider models
Interior adjusting is enclosed, realizes material morphology and performance change and different tissues regeneration requirements and Treatment need by adjusting material parameter
Dynamic Matching.It can be saved for a long time by drying and dehydrating processing when the composite gel material is as product, ensure that its future
The feasibility of clinic conversion.
Compared with current material and preparation method, the invention has the following beneficial effects:
1. the raw material sources that the present invention prepares plural gel are abundant, low in cost and environmentally friendly, harmless；
2. plural gel preparation cost of the present invention is cheap, simple process is environmental-friendly, lower to equipment requirement, easily realizes big rule
Mould production；
3. being selected by raw material and preparation method, plural gel prepared by the present invention can have both biological safety, degradability,
Promote Various Tissues regeneration, promote vascularization, is antibacterial, inhibiting the multiple performances such as cancer cell, there is disease treatment and guidance tissue
Regenerated double action, and various performances are easy to regulate and control to can be used for organizational project, 3D printing, dressing, medicine to meet different demands
The fields such as object sustained release, Various Tissues defect repair, infection and sepsis treatment, oncotherapy.
Detailed description of the invention
Fig. 1 is a kind of scanning electron microscope (SEM) photograph for plural gel (the pure magnesium of polyvinyl alcohol -) that the embodiment of the present invention 1 provides.
Specific embodiment
Technical scheme of the present invention is further explained with reference to the accompanying drawings and examples.
Embodiment 1:
Polyvinyl alcohol 10% is added in deionized water by mass percentage, heating stirring is completely dissolved to it, and it is water-soluble to obtain gel
Liquid；20 DEG C place 1 hour after obtain thick liquid；150 μm of average grain diameter of pure magnesium granules 5% are added to by mass percentage
In thick liquid, after being thoroughly mixed, 24 hours is stood at 4 DEG C, obtains the medical plural gel of more biological functions.It is soaked in
In deionized water, the water of absorbable 2 times of own wt when balance, testing its compression strength after water suction balance is 10 ± 4kPa, is broken
Splitting elongation percentage is 200 ± 25%.Other conditions are identical, do not add the polyvinyl alcohol gel conduct pair prepared in the case of pure magnesium granules
According to group.
The microscopic appearance of the scanning electron microscopic observation plural gel is utilized after freeze-drying.Referring to attached drawing 1, it is the present embodiment
A kind of scanning electron microscope (SEM) photograph of the plural gel (the pure magnesium of polyvinyl alcohol -) provided；As seen from Figure 1, magnesium granules are uniform in plural gel
It is distributed in the hole wall of gel-forming, is partially wrapped up by gel and be fixed on original position；Plural gel is in level porous structure, into one
Step demonstrates prepared plural gel in-situ preparation level porous structure.
Utilize the degradation property of immersion in vitro experiment test material.Using serum-free MEM culture medium as soak (pH=
7.2~7.4), impregnating ratio is 1.25cm2/ ml, the preceding gel of immersion fully absorb MEM and reach balance.It is updated daily during immersion
Soak.It changes within 1 day, 7 days and 28 days before liquid and measures the pH value and magnesium ion concentration of soak, the results are shown in Table 1, plural gel
The pH value and magnesium ion concentration of the soak of group are apparently higher than control group, show that the magnesium metal inside plural gel can degrade,
And long-term controlled release hydroxide ion and magnesium ion, adjust the ionic microenvironments of surrounding.
It is (small to NIH3T3 cell to material extract according to national standard GBT16886.5-2003 BiologicalEvaluationofMedicalDevice
Mouse fibroblast cell) cytotoxicity evaluated, the opposite proliferation rate of plural gel group is 105% as the result is shown, is shown multiple
It closes gel and has good biological safety.
Table 1 impregnate 1 day, 7 days with different groups of soak pH value and magnesium ion concentration at 28 days
。
Embodiment 2:
Sodium alginate 2.5% is added in deionized water by mass percentage, heating stirring is completely dissolved to it, then by gel
Aqueous solution is cooled to 25 DEG C, obtains thick liquid；By mass percentage by 150 μm of magnesium zinc (Mg-5Zn) alloying pellets of average grain diameter
8% is added in thick liquid, and after being thoroughly mixed, 0.1M calcium chloride solution is added, and gel is full cross-linked, obtains after dry
More medical plural gels of biological function.It is soaked in deionized water, the water of absorbable 10 times of own wt when balance, water suction balance
After test its compression strength be 1 ± 0.3kPa, fracture elongation be 110 ± 15%.Other conditions are identical, do not add magnesium-zinc alloy
The seaweed acid gel prepared in the case of particle is as a control group.
Immersion in vitro is carried out using the condition of embodiment 1, changes within 28 days before liquid that measure magnesium ion and zinc ion in soak dense
Degree.As the result is shown plural gel group magnesium ion concentration be 95 ± 14 mg/L, zinc ion concentration be 8 ± 4mg/L, control group magnesium from
Sub- concentration is 18 ± 5mg/L, and no zinc ion shows that magnesium-zinc alloy particle can degrade in plural gel, and release biology for a long time
Functional ion is to ambient enviroment.
According to national standard GBT16886.5-2003 BiologicalEvaluationofMedicalDevice, using NIH3T3 cell to material extract
Cytotoxicity evaluated, as the result is shown the opposite proliferation rate of plural gel group be 100 ± 8%, plural gel has well
Biological safety.And using leaching liquor to test cell activity (opposite proliferation rate) after MC3T3 osteoblasts cultivation 3 days, knot
Fruit shows that plural gel group cell activity is 125 ± 11%, and control group is 103 ± 4%, shows that plural gel leaching liquor can promote into
Bone cell proliferation.
Utilize Hanks ' simulated body fluid to extract two groups of materials, by leaching liquor and staphylococcus aureus suspension into
Row is mixed and is cultivated at 37 DEG C 24 hours, and mixed bacterium solution is then coated on agar plate and is cultivated, is carried out after 24 hours
Clump count.The quantity of plural gel group Colony Forming Unit (CFU) is substantially less than control group as the result is shown, shows compound solidifying
Glue leaching liquor has bacteriostasis to staphylococcus aureus.
Embodiment 3:
Gelatin 20% is added in deionized water by mass percentage, heating stirring is completely dissolved to it, obtains gel solution；
Obtained gel solution is cooled to 37 DEG C；100 mesh zinc-copper (Zn-2Cu) alloy powders 10% are added to by mass percentage
In liquid, under the conditions of being sufficiently stirred, 20% glutaraldehyde solution for being added 1 wt%, is obtained after Quick cross-linking compound by mass percentage
Gel, plural gel is placed at 4 DEG C 24 hours it is full cross-linked, is then sufficiently rinsed with deionized water it is dry after, obtain and give birth to more
The medical plural gel of object function.It is soaked in deionized water, plural gel can absorb the water of 4.5 times of own wt when balance, inhales
It is 100 ± 40kPa that its compression strength is tested after water balance, and fracture elongation is 50 ± 7%.Other conditions are identical, do not add zinc
The gelatin gel prepared in the case of copper alloy particle is as a control group.
Immersion in vitro experiment is carried out using the condition of embodiment 1.Change within 28 days before liquid measure in soak zinc ion and copper from
Sub- concentration.Plural gel group zinc ion concentration is 30 ± 5mg/L as the result is shown, and copper ion concentration is 0.11 ± 0.04mg/L, right
According to group without zinc ion, without copper ion.Meanwhile according to national standard GBT16886.5-2003 BiologicalEvaluationofMedicalDevice, utilize
NIH3T3 cell evaluates the cytotoxicity of material extract, and the opposite proliferation rate of plural gel group is as the result is shown
105 ± 6%, have good biological safety.And utilize leaching liquor to HUVEC cell in Matrigel®Surface at pipe activity into
Row test, plural gel composition pipe area, quantity, pipe thickness and intersection dot density are significantly higher than control group, table as the result is shown
Bright plural gel leaching liquor can promote HUVEC cellular vascular relative to simple gel.Material is pressed down using the method for embodiment 2
Bacterium performance is measured.The quantity of plural gel group Colony Forming Unit (CFU) is substantially less than control group as the result is shown, shows multiple
Closing gel leaching liquor has bacteriostasis to staphylococcus aureus.
Rat skin defect is repaired using two groups of materials.2 centimetres of diameter of full thick skin is prepared in rat back
Defect, will be 4 millimeters thick, and the plural gel and simple gel that 2 centimetres of diameter are implanted into defect point respectively, then use Tegaterm
Film and bandage carry out protection fixation.Defect size is measured after 14 days, shows the remaining defect size of plural gel group
It is significantly less than control group.Histology and immunohistochemical analysis show that the blood vessel number of plural gel group neoplastic skin is apparently higher than pair
According to group (there is significant difference).
Embodiment 4
By the gelatinization solution of the sodium alginate soln of mass fraction 2.5% and 10% cornstarch of mass fraction, 1:1 exists by volume
It is sufficiently mixed at 50 DEG C, is subsequently cooled to 37 DEG C；By 100 μm of magnesium copper (Mg-1Cu) of average grain diameter and magnesium strontium (Mg-2Sr) alloyed powder
End 5% is added in liquid by mass percentage after evenly mixing (mass ratio 1:1), after being thoroughly mixed, by mass percentage
10% is added the glutaraldehyde solution of 1 wt%, obtains plural gel after gel Quick cross-linking, and plural gel is placed 24 hours at 4 DEG C
It is full cross-linked, it is then immersed in the CaCl of 0.1M212 hours secondary cross-linkings, finally sufficiently rinse drying with deionized water in solution
Afterwards, the medical plural gel of more biological functions is obtained.It is soaked in deionized water, the water of absorbable 10 times of own wt when balance,
It is 800 ± 130kPa that its compression strength is tested after water suction balance, and fracture elongation is 40 ± 5%.Other conditions are identical, do not add
The gel prepared in the case of alloying pellet is as a control group.
Immersion in vitro is carried out using the condition of embodiment 1, measures magnesium ion, copper ion and strontium in soak before changing within 28 days liquid
Ion concentration.Plural gel group magnesium ion concentration is 125 ± 14 mg/L as the result is shown, and copper ion concentration is 0.13 ± 0.03mg/
L；Strontium ion concentration is 0.5 ± 0.17mg/L, and control group magnesium ion concentration is 18 ± 5mg/L, no copper ion and strontium ion, is shown
Alloying pellet can degrade in plural gel, and discharge a variety of Biofunctional ions for a long time to ambient enviroment.
According to national standard GBT16886.5-2003 BiologicalEvaluationofMedicalDevice, using NIH3T3 cell to material extract
Cytotoxicity evaluated, as the result is shown the opposite proliferation rate of plural gel group be 115 ± 9%, have it is good biology peace
Quan Xing.It is multiple as the result is shown and using leaching liquor to test cell activity (opposite proliferation rate) after MC3T3 osteoblasts cultivation 3 days
Closing gel group cell activity is 130 ± 12%, and control group is 105 ± 8%, shows that plural gel leaching liquor can promote osteoblast increasing
It grows.Using leaching liquor to HUVEC cell in Matrigel®Surface carry out culture test cell at pipe activity, it is compound as the result is shown
Gel group cell is significantly higher than control group at pipe area, quantity, pipe thickness and intersection dot density.Utilize the method for embodiment 2
Material bacteriostasis property is measured.The quantity of plural gel group Colony Forming Unit (CFU), which is substantially less than, as the result is shown compares
Group shows that plural gel leaching liquor has bacteriostasis to staphylococcus aureus.
Bone defect model is prepared in rabbit femoral metaphysis.Wherein plural gel and simple gel are implanted to bone by one group of experiment
In defect, micro-CT analysis and histologic analysis are carried out after two months.As the result is shown at bone amount and new around plural gel group
Angiogenic quantity is significantly higher than simple gel group, a large amount of new Bone Ingrowth plural gel groups.Another set experiment by plural gel and
Simple gel is implanted in bone defect after impregnating in a certain concentration staphylococcus aureus suspension, carries out micro- after two months
CT analysis and histologic analysis.Plural gel group around has a large amount of area of new bone without obvious inflammation and infection reaction as the result is shown.And
Simple gel group then shows apparent infection, around almost without New born formation, and bone dissolution has occurred.
Claims (10)
1. a kind of medical plural gel with more biological functions, it is characterised in that: it is with biodegradable big point after crosslinking
Sub- gel is continuous substrate phase, and the biodegradable metal/alloy particle for accounting for mass percent 5~50% is uniformly distributed in continuously
In substrate phase；The biodegradable macromolecular gel includes gelatin, collagen, alginic acid, polyvinyl alcohol, polyethylene glycol, shallow lake
Powder, cellulose, chitosan, hyaluronic acid, chondroitin sulfate；The partial size of the biodegradable metal/alloy particle is 10
~1000 μm, including pure zinc, kirsite, pure magnesium, magnesium alloy；Itself weight of water absorption >=1 times of the medical plural gel
Amount, the compressive strength after water suction balances is 0.1~1000kPa, and fracture elongation is 30~1000%.
2. a kind of medical plural gel with more biological functions according to claim 1, it is characterised in that: the shallow lake
Powder includes corn, potato, wheat, sweet potato, sweet potato, cassava, glutinous rice ative starch and its modified starch.
3. a kind of medical plural gel with more biological functions according to claim 1, it is characterised in that: described is pure
Zinc, Zn-ef ficiency mass fraction > 99%；The kirsite, wherein the alloying element for being 1~50% containing mass fraction summation,
Including copper, magnesium, silver, manganese, selenium, strontium, calcium, iron, zirconium, silicon；The pure magnesium, magnesium elements mass fraction > 99%；The magnesium closes
Gold, wherein the alloying element for being 1~50% containing mass fraction summation, including zinc, copper, silver, manganese, selenium, strontium, calcium, iron, zirconium, silicon.
4. a kind of preparation method of the medical plural gel with more biological functions, it is characterised in that include the following steps:
(1) by mass percentage 1~50%, biodegradable macromolecular gel is add to deionized water, heating, stirring bar
Gel solution is obtained under part, obtains thick liquid after cooling；The biodegradable macromolecular gel includes gelatin, glue
Original, alginic acid, polyvinyl alcohol, polyethylene glycol, starch, cellulose, chitosan, hyaluronic acid, chondroitin sulfate；
(2) by mass percentage 0.05~50%, degradable metal/alloying pellet is added to the thick liquid that step (1) obtains
In, the partial size of the biodegradable metal/alloy particle is 10~1000 μm, including pure zinc, kirsite, pure magnesium, magnesium close
Gold；Through being thoroughly mixed, stands under conditions of temperature is 0~20 DEG C, had after the abundant self-crosslinking of gel and after drying
There is the medical plural gel of more biological functions；Or it self-crosslinking is obtained plural gel is placed in cross-linking agent solution to carry out secondary friendship
Connection, the crosslinking agent includes glutaraldehyde, formaldehyde, Geniposide, square diethyl phthalate, glyoxal, oxalic acid, β-phosphoglycerol, water-soluble
Property carbodiimide, or contain calcium ion, zinc ion, magnesium ion, ferrous ion, strontium ion, tripolyphosphate radical ion, sulfate radical
The aqueous solution of ion, citrate ion one of which；Again after deionized water is sufficiently cleaned and dried, obtain that there are more biological function
The medical plural gel of energy.
5. a kind of preparation method of medical plural gel with more biological functions according to claim 4, feature exist
In: the starch includes corn, potato, wheat, sweet potato, sweet potato, cassava, glutinous rice ative starch and its modified starch.
6. a kind of preparation method of medical plural gel with more biological functions according to claim 4, feature exist
In: the pure zinc, Zn-ef ficiency mass fraction > 99%；The kirsite, wherein being 1~50% containing mass fraction summation
Alloying element, including copper, magnesium, silver, manganese, selenium, strontium, calcium, iron, zirconium, silicon；The pure magnesium, magnesium elements mass fraction >
99%；The magnesium alloy, wherein containing mass fraction summation be 1~50% alloying element, including zinc, copper, silver, manganese, selenium,
Strontium, calcium, iron, zirconium, silicon.
7. a kind of preparation method of the medical plural gel with more biological functions, it is characterised in that include the following steps:
(1) by mass percentage 1~50%, biodegradable macromolecular gel is add to deionized water, heating, stirring bar
Gel solution is obtained under part, obtains thick liquid after cooling；The biodegradable macromolecular gel includes gelatin, glue
Original, alginic acid, polyvinyl alcohol, polyethylene glycol, starch, cellulose, chitosan, hyaluronic acid, chondroitin sulfate；
(2) in the case where temperature is 0~50 DEG C of stirring condition, by mass percentage 0.1~50%, by degradable metal/alloying pellet
It is added in the thick liquid that step (1) obtains, crosslinking agent is added after being sufficiently mixed, then under conditions of temperature is 0~10 DEG C
6~24 hours are stood, the plural gel after being crosslinked；The partial size of the biodegradable metal/alloy particle be 10~
1000 μm, including pure zinc, kirsite, pure magnesium, magnesium alloy；The crosslinking agent includes glutaraldehyde, formaldehyde, Geniposide, side's acid two
Ethyl ester, glyoxal, oxalic acid, β-phosphoglycerol, water-soluble carbodiimide, or contain calcium ion, zinc ion, magnesium ion, ferrous iron
Ion, strontium ion, tripolyphosphate radical ion, sulfate ion, citrate ion one of which aqueous solution；
(3) plural gel that step (2) obtains sufficiently is cleaned and dried with deionized water, or that plural gel is placed in crosslinking agent is molten
It is sufficiently cleaned and dried with deionized water again after carrying out secondary cross-linking in liquid, obtains the medical plural gel with more biological functions；
The crosslinking agent includes glutaraldehyde, formaldehyde, Geniposide, square diethyl phthalate, glyoxal, oxalic acid, β-phosphoglycerol, water-soluble carbon
Diimine, or containing calcium ion, zinc ion, magnesium ion, ferrous ion, strontium ion, tripolyphosphate radical ion, sulfate radical from
The aqueous solution of son, citrate ion one of which.
8. a kind of preparation method of medical plural gel with more biological functions according to claim 7, feature exist
In: the starch includes corn, potato, wheat, sweet potato, sweet potato, cassava, glutinous rice ative starch and its modified starch.
9. a kind of preparation method of medical plural gel with more biological functions according to claim 7, feature exist
In: the pure zinc, Zn-ef ficiency mass fraction > 99%；The kirsite, wherein being 1~50% containing mass fraction summation
Alloying element, including copper, magnesium, silver, manganese, selenium, strontium, calcium, iron, zirconium, silicon, rare earth element；The pure magnesium, magnesium elements quality
Score > 99%；The magnesium alloy, wherein containing mass fraction summation be 1~50% alloying element, including zinc, copper, silver,
Manganese, selenium, strontium, calcium, iron, zirconium, silicon.
10. a kind of application of the medical plural gel with more biological functions as described in claim 1, it is characterised in that: use
In tissue engineering bracket material, 3D printing material, dressing is used for Repair of tissue defect, infection, purulence as Implantable Medical Device
Viral disease, the local treatment of tumour.
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| CN113354839A (en) * | 2020-08-26 | 2021-09-07 | 兰州大学 | Collagen-silver nanoparticle composite gel, preparation method and application |
| CN112451742A (en) * | 2020-11-24 | 2021-03-09 | 北京大学深圳医院 | Preparation method of degradable metal-organic matter composite bone repair material |
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