CN102634041B - Preparation method of silk fibroin/ polyurethane composite hydrogel, and application thereof - Google Patents
Preparation method of silk fibroin/ polyurethane composite hydrogel, and application thereof Download PDFInfo
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- CN102634041B CN102634041B CN 201110444423 CN201110444423A CN102634041B CN 102634041 B CN102634041 B CN 102634041B CN 201110444423 CN201110444423 CN 201110444423 CN 201110444423 A CN201110444423 A CN 201110444423A CN 102634041 B CN102634041 B CN 102634041B
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Abstract
The invention relates to a preparation method of silk fibroin/ polyurethane composite hydrogel, and the application of the compound, which is applicable to the preparation of artificial nucleus. The preparation method of the silk fibroin/ polyurethane composite hydrogel comprises the steps of: carrying out a reaction on isophorone diisocyanate(IPDI), polypropylene glycol (PPG), polyethylene glycol, dimethylolpropionic acid (DMPA), 1, 4-butylene glycol, acetone and catalyst stannous octoate to obtain polyurethane hydrogel; treating bombyx mori silk to obtain a silk fibroin solution; and mixingthe silk fibroin solution and the polyurethane hydrogel according to the proportion of 1:1 to obtain the silk fibroin/ polyurethane composite hydrogel. The invention is applied to the fields such as the artificial nucleus and the like.
Description
Technical field
The present invention relates to preparation method and the application thereof of a kind of silk fibroin/urethane composite aquogel, be applicable to the preparation of artificial nucleus.
Background technology
The backbone degenerative disease is that a kind of common disease, especially cervical spondylosis and lumbar spondylosis sickness rate are the highest, and the sickness rate of the two accounts for adult's 60% ~ 80%.Some the occupation in addition can be up to more than 90%.Epidemiological study is the result show, neck-shoulder pain, lumbago and leg pain has become the highest occupational disease of sickness rate in worldwide at present.Neck-shoulder pain, lumbago and leg pain can occur at it in nearly 75% ~ 85% people in life.The American National statistical information shows that the Annual occurence rate of lumbago and backache is 15% ~ 20%, is the modal reason that causes limitation of activity among the crowd below 45 years old.European countries' statistical result showed, the Annual occurence rate of neck shoulder lumbago and backache is 25% ~ 45%.The elderly of China more than 60 years old reached 1.3 hundred million, accounts for 1/10 of national population, and old backbone degenerative disease is a major reason that causes the neck-shoulder pain, lumbago and leg pain sickness rate to increase.
Intervertebral disc degeneration is prerequisite and the pathologic basis that causes the backbone degenerative disease; Intervertebral disc degeneration (Intervertebral Disc Degeneration, IVDD) be the part of body regression, its mechanism is the reduction of nutritive substance in the intervertebral disk, the susceptibility forfeiture of the minimizing of active cells quantity or extracellular matrix in the dish, the reduction of long-chain protein-polysaccharide and water-content and active cells quantity reduce, and and then affect the function of dish inner cell, cause the change of intervertebral disk shape and the forfeiture of mechanical function.Backbone is comprised of 24 vertebras and a rumpbone as the system of a complexity, and their connection is by little joint, intervertebral disk, and ligament and muscle on every side thereof are finished.Replace wherein any part, all can cause the reaction of whole system.Therefore, the artificial intervertebral disk physiological property that must have similar original intervertebral disk is with the activity of keeping backbone and stable.The binding of centrum is to be made of the articuli intervertebrales that intervertebral disk and upper inferior articular process thereof consist of.With advancing age, intervertebral disc degeneration is inevitable.It, is difficult to stop or reverse in case regression occurs because the disc tissue regenerative power is limited.Experiment showed, that the mobility of centrum will improve 38% ~ 100% after the excision nucleus pulposus, the collegen filament that form fibrous ring will make along the direction of forcing spindle the outside outside bulging of collegen filament, the inner inside bulging of collegen filament.These factors have been cut down the anti-shearing stress of fibrous ring, finally cause tearing and protrusion of intervertebral disc of fibrous ring.And after a complete implanted model of allogeneic nucleus pulposus, the process that above intervertebral disk retrogression changes has slowed down.
Along with the intensification that spinal biomechanics mechanism is familiar with and the development of materialogy, artificial nucleus replacement is considered to substitute the regression of spinal fusion treatment waist sacral and becomes lumbago caused effective ways.As the artificial nucleus implant, at first will guarantee has identical or similar biomechanical function with the nucleus pulposus of human body, stable with the complete sum that keeps intervertebral disk.In addition, implant also needs not play rejection with human body, is nontoxicity and non-carcinogenesis to human body.Implant must can bear certain pressure, and according to statistics, an average nucleus pulposus bears the physiology load every year 200 ten thousand times, and implant can bear the physiology load 1,000,000,000 times surpassing in the work-ing life in 40 years, and this is only, and we are desired.The material of this prosthese is to be made of small sheet particle chains, so just has the low consumed characteristic of low wearing and tearing.Implant also should have certain hardness, to avoid ambient pressure to the erosion of its compression and osseous tissue.The size of implant must and the intervertebral disk implanted meet, can not be excessive can not be too small, otherwise its adjacent endplate is born the pressure inequality, can be subject to corresponding damage.At last, must reach minimizing of operative approach in the design of implant, to reduce the destruction to surrounding tissue.Finite element analysis shows that nucleus pulpous cavity filled-type prosthese has the behavior that mechanicalness is repaired fibrous ring, but does not have such function without the prosthese of lacuna type.The load that implant bears, the pressure of generation acts on next vertebra.If pressure is greater than the intensity of vertebra, vertebra will sink gradually, if this pressure is less, vertebra can change according to the distribution of pressure for more effectively load-bearing.
Basic Design thinking and evolution according to artificial nucleus are divided into following a few class: preliminary shaping artificial nucleus, situ perfusion shaping artificial nucleus and half form artificial nucleus.(1) the preliminary shaping artificial nucleus is that the prosthese that has formalized is put into intervertenral space, and " the earliest the Stainless Steel Ball of artificial nucleus design on the human history namely belongs to this kind of.He had reported the result of study of inserting neck, Intervertebral space with Stainless Steel Ball behind discectomy in 1966.Altogether finish 125 cases, use 191 prostheses, find that postoperative 4-7 only has 12% intervertenral space thickness to be kept, other great majority since heavily stressed Metal Ball that make of contact surface embed in the centrum.This prosthese is abandoned subsequently.And silica gel afterwards, all be not eliminated because meeting the basic character of normal human's nucleus pulposus.(2) situ perfusion shaping artificial nucleus mentality of designing is that it is moulding to be frozen in position the semi-solid state polymerization with the intervertenral space behind the polymer precursor injection excision regression nucleus pulposus.The major advantage of using this prosthese is to adopt Percutaneous Techniques, having the little and original position of surgical injury to be frozen into semi-solid characteristics closely is affixed prosthese and nucleus pulposus cavity wall, stability, compliance is good, has more uniform stress dispersion effect, can recover normal length and the tension force of fibrous ring, operative results is fast, can obviously reduce the outstanding rate of prosthese.But can not avoid in the injection liquid polymer process overflowing from Anular incision and the fibrous ring crack that may exist.It is the most frequently used that to can be made into situ perfusion shaping artificial nucleus material be silica gel and polyurethane.Silica gel is nontoxic, histocompatibility good, also non-carcinogenesis.But silica gel is easily aging, and the postoperative long-term observation has the intervertenral space marginal density to increase report with narrow gaps.Urethane has better resistance to pressure and surge capability than silicon rubber, and can control polymerization velocity and the thermopositive reaction of monomer, but its antifatigue and wear-resistant ability.(3) in view of the weak point of above-mentioned two kinds of prosthese types and material, marginal kind of design occurring is the half form artificial nucleus.Put into its profile of process or large I changes according to actual needs at prosthese, put into the required profile of rear maintenance or size.A kind of is the half form gel prosthese of putting into through processed, puts into gel aquation behind the intervertenral space, expansion; Another is to put into the air bag of Foldable and deformable to the nucleus pulpous cavity of extracing, but the original position of reinjecting is frozen into semi-solid macromolecular material air bag is fully expanded, and then makes the intervertebral disk that subsides recover due height.
Ray in 1988 etc. have designed twin columns shape artificial nucleus, and the Nuclectomy postoperative is implanted this kind prosthese from the way of escape, with the thin screw of a kind of length prosthese is tied down again, is fixed between the upper and lower soleplate.This thin screw is to be made by polyglycolic acid, can also promote the surrounding tissue growth to repair, and the periprosthetic capsular of implantation has semipermeability, and the inside parcel can absorb the jelly of moisture, is eliminated owing to packing technique is immature afterwards.Normal disc has periodic pressure change when Body Position Change and motion, liquid is flowed between inside and outside the intervertebral disk, makes intervertebral disk finish the nutrition exchange.Those nucleus prosthesis that do not contain effective water constituent could reduce the nutrition supply of intervertebral disk, cause carrying out property of the intensity decline of avascular fibrous ring! The long-term effect of impact displacement.For this problem, nineteen ninety Bao and Higham taken the lead in developing a kind of under physiological loads water content be approximately 70% hydrogel as the nucleus pulposus implant, Bao and Higham confirm that first this prosthese can simulate the liquid statics function of human body nucleus pulposus-correspondingly absorb or discharge with the variation of backbone mechanical load moisture in the 11st North America backbone association annual meeting in 1996, biomechanics Research verified it can recover the anatomical physiology function of lesion segment intervertebral disk, the baboon animal model experiment shows rejection does not occur to have preferably biocompatibility.
20th century the mid-90 Ray etc. cooperates with Raymedia company, use for reference the people's such as Bao achievement, its product is improved, and usefulness has extensibility but does not have elastic polyethylene fibre film wrapped hydrogel to make shape like artificial nucleus PDN (the Prosthetic Disc Nucleus of pincushion; Raymedia; Bloomington, Minnesota), minimize before after hydrogel compression, the processed prosthese being implanted, the platinum iridium alloy line of putting into wherein is convenient to art x-ray location and Follow-up After, prosthese is put into rear polyethylene fibre film and is allowed moisture to enter, absorbed moisture expands, and most of hydration is finished in the 24h after surgery, expands but will just can reach farthest through four or five days.Improved simultaneously operation method, from way of escape Wicresoft Nuclectomy postoperative, put into prosthese after enlarging former otch through the former otch of fibrous ring or with the PDN expander special, the prosthese putting position is changed into and centrum trailing edge parallel direction side by side by fore-and-aft direction, thereby has reduced the outstanding of implant.For avoiding Anular disruption, prosthese is implanted rear with the otch on the sticking patch stitching fibrous ring.Recently, Dooris etc. carry out external biological mechanical test proof and take the way of escape to insert prosthese, do not damage anterior longitudinal ligament, and postoperative can reduce little joint, pedicle of vertebral arch mechanical load.The Wilke of ULM, Germany university etc. carry out the biomechanics test at corpse L4-5 intervertebral disk, L4-5 semi-vertebral plate Nuclectomy postoperative is put into PDN, the result shows that PDN can make the range of movement of backbone remain on normal level, also can increase L4-5 disc height under the stress state, but weak point is fully aquation of PDN, can not recover the due height of intervertebral disk fully.Up to now, only has PDN through testing widely and drop into clinical application.This prosthese has gone through to carry out clinical trial in the U.S. at present, in first artificial intervertebral disk annual meeting in North America of holding in October, 1999, Raymedia company 101 cases of report have been carried out cervical disc, in the case that does not have prosthese to deviate from, prosthese occurs and deviates from pain relief behind the overwhelming majority corrective surgery, 17 examples.Schromayer in calendar year 2001 joint of vertebral column shaping annual meeting reported 350 case Follow-up results, before the art, postoperative 2 years, 4 years Oswestry of postoperative be respectively 52%, 10%, 8.3%; Prolo scoring mean value is respectively 4.5,8.8,9.1; Before the lateral lumber spine X-ray film shows lesion segment disc height art, to be respectively 8.7,10.2,10.5mm. in 4 years be that postoperative can obviously increase the lesion segment disc height for postoperative 1 year, postoperative, prostheses migration obviously reduced after operation method improved.From above report, there is a problem-prostheses migration that attracts people's attention in artificial nucleus replacement, and in a single day fibrous ring breaks, just prostheses migration may occur.These complication of factors influence such as operation approach, size incision, fibrous ring degree of degeneration, prosthese putting position, Bertagnoli proposes side the place ahead through iliacus approach (ALPA), longitudinal ligament before and after this method is not damaged, prostheses migration obviously reduces.
Although many researchs about artificial nucleus are arranged in recent years, and obtain certain progress, we find that also artificial nucleus clinically mostly is prefabricated, and the progress of injecting type artificial nucleus is little.The research of injecting type artificial nucleus becomes the new problem of present artificial nucleus research.
Above three-type-person worker's nucleus pulposus respectively has shortcoming: preliminary shaping artificial nucleus and human body do not have good suitability; Situ perfusion shaping artificial nucleus is can not avoid in the injection liquid polymer process overflowing from Anular incision and the fibrous ring crack that may exist; There are the problems such as a problem-prostheses migration that attracts people's attention and soleplate sinking in the half form artificial nucleus.
Summary of the invention
Technical problem to be solved by this invention provide a kind of technique and formulating of recipe rationally, preparation method and the application thereof of the human body suitability is good, make that wearing and tearing behind the artificial nucleus are little, safety and stability, life-time service are safe and reliable silk fibroin/urethane composite aquogel.
The present invention solves the problems of the technologies described above the preparation method that the technical scheme that adopts is a kind of silk fibroin/urethane composite aquogel, and its preparation process is:
A, under the nitrogen protection condition, be that the molecular weight of 2000 polypropylene glycol, 120 weight parts is that the molecular weight of 2000 polyoxyethylene glycol or 240 weight parts is 1000 polyoxyethylene glycol with the molecular weight of the isophorone diisocyanate of 133 weight parts and 180 weight parts, add in the there-necked flask, 88-95 ℃ of lower reaction 2h obtains primary product;
1 of b, the dimethylol propionic acid that in primary product, adds 16-17 weight part or 20.9-21.1 weight part, 9-18 weight part, 4-butyleneglycol, acetone, the inferior tin of octoate catalyst, react 3h under the 65-72 ℃ of condition, obtain polyurethane hydrogel, wherein, the amount of the inferior tin of octoate catalyst is that the isophorone diisocyanate of every 13.3g adds one;
C, take by weighing 10 g after the silkworm silk shredded, at the Na of 0.5wt%
2CO
3Boil in the aqueous solution and removed silk gum in 40-60 minute, then use the deionized water repetitive scrubbing for several times, until the surface does not have satiny sensation, obtain washing silk;
D, will wash silk and in 40 ℃ of vacuum drying ovens, place and under 40 ℃ of constant temperatures, be dissolved in the lithium bromide water solution of 9 mol/L after 24 hours, obtain silk fibroin solution;
E, be the dialysis tubing of 8000-14000 with silk fibroin solution with the molecular weight cut-off of packing into after the filter-cloth filtering, be placed in the large beaker that fills with deionized water dialysis three days, changed water one time every 12 hours in the process, obtain dialyzate;
F, dialyzate is poured in the centrifuge tube, under 6000 rpm rotating speeds, removed insoluble substance in centrifugal 10 minutes, obtain silk fibroin protein solution, be placed in 4 ℃ the refrigerator and preserve;
G, silk fibroin protein solution and the polyurethane hydrogel volume ratio according to 1:1 is mixed, obtain silk fibroin/urethane composite aquogel.
As preferably, in the polyurethane hydrogel of the present invention, isocyano and hydroxyl ratio are 1.4:1-1.6:1.
As preferably, the amount of acetone of the present invention is: in the solid matters of 50 grams, add 30-40ml.
As preferably, the present invention adds the medicinal barium sulfate powder in step g.
For avoiding toxicity, make material that good biocompatibility be arranged, condition of molding is reduced, can self-vulcanizing.We adopt nontoxic polypropylene glycol and polyoxyethylene glycol raw material.
Polyol compound shared ratio in the synthesizing formula of urethane is maximum, other amounts of components are all take it as benchmark in the prescription, when component design, the factor that takes into full account has: the price of polyol compound, source, meet requirement and the purposes of the final performance of polyurethane material, the functionality of polyvalent alcohol, molecular weight and viscosity are suitable.Good with the mutual capacitive of other raw materials such as isocyanic ester, catalyzer, satisfy some particular requirement of polyurethane material: solvent resistance, water tolerance.Polypropylene glycol is a kind of polyether glycol, and the polyurethane product synthetic take polyether glycol as raw material has preferably flexibility, hydrolytic resistance, rebound resilience and resistance to low temperature.
The scope of polypropylene glycol molecular weight is generally at 400-5000, and along with polyethers di-alcohol molecular weight increases, the polyurethane product pliability, elasticity and the low temperature properties that make are better.Here select polyether glycol (PPG: i.e. N-220), and molecular weight is 2000 ± 100.
For making material that more satisfactory mechanical property be arranged, we adopt the PPG(polyether glycol) as flexible polyurethane section raw material, the polyoxyethylene glycol of PEG(molecular weight 2000) the hydrogel wetting ability is provided.
The inferior tin nontoxicity of octoate catalyst and corrodibility can be used for medical treatment product.The selection of solvent.
Selective solvent must consider following some: do not contain with material or the content of isocyanate reaction very low.On the impact of isocyanic ester chemistry reaction, to the harm of environment.The boiling point of solvent and evaporation rate.Dilution effect and cost.
Intensive polar solvent acetone: boiling point is low as far as possible, and it is removed easily; All be good solvent to chainextender and performed polymer.
For molecular weight and the soft or hard section ratio of regulating urethane, improve material property, also will use micromolecular chainextender during synthetic performed polymer, chainextender essence is that the polyurethane macromolecular of small molecule chain extender and end-NCO group further reacts the larger macromole of generation.Select chainextender to consider: reactive behavior is moderate, can improve the thermotolerance of urethane.Amine chain extender toxicity is large, and what we adopted is alcohols chainextender Isosorbide-5-Nitrae-butyleneglycol, and it can regulate the soft durometer of urethane, can increase the Interpolymer Association chance, is conducive to improve mechanical property.
The application of the silk fibroin of the present invention's preparation/urethane composite aquogel in the preparation of artificial nucleus prosthese.
The application of the silk fibroin of the present invention's preparation/urethane composite aquogel in the artificial skin preparation.
The application of the silk fibroin of the present invention's preparation/urethane composite aquogel in the preparation of human body soft tissue charges.
The application of the silk fibroin of the present invention's preparation/urethane composite aquogel in the artificial breast prosthesis preparation.
The silk fibroin of the present invention's preparation/application of urethane composite aquogel in orthopedic injection-type charges.
The present invention compares with existing technology, has the following advantages and characteristics:
The present invention is with silk fibroin and the urethane material as artificial nucleus, emphasis is to use silk fibroin and urethane monomer as raw material, design at room temperature is injected into nucleus pulposus with liquid state or semi-solid, the wound of bringing when reducing Operation, and it is few formally to be seen in so far the real injecting type artificial nucleus of studying of report.Be applied to clinical just still less.And application silk fibroin and urethane are rarer as the material of artificial nucleus.This is for comprehensive further investigation injecting type artificial nucleus or far from being enough, nor can satisfy clinically the demand to the injecting type artificial nucleus, and these two aspects problem in science of solving of this research emphasis just.The present invention is situ perfusion type artificial nucleus, and its structure is made of polymer, can become solid-state after it is injected when semi-solid state, polymerization forming, and allow the surgeon with the implantation of minimal damage degree, kept the integrity of posterior longitudinal ligament, and reduced implant and transplanted risk.
The present invention adopts a kind of homemade silk fibroin protein solution and homemade base polyurethane prepolymer for use as solution, the mechanical property of the biocompatibility that the zygomite fibroin is good and urethane excellence, solve the problem on many theory and technologies, developed a kind of new silk fibroin that is applied to intervertebral disk/urethane composite aquogel artificial nucleus; If when synthetic, to add the medicinal barium sulfate powder, make synthetic hydrogel have the iconography visuality.Here, residual isocyanate groups react with on amino group and the urethane on the silk fibroin, chemically crosslinked becomes allophanate groups.The other N on the molecular chain, O and hydrogen atom form hydrogen bond, also are a kind of crosslinked, are physical crosslinkings.Its exploitation to injecting type artificial nucleus prosthese is significant.
Characteristic of the present invention is to use silk fibroin and urethane as the material of artificial nucleus, take full advantage of the natural structure properties of silk fibroin and good biocompatibility, in conjunction with the good mechanical property of medical polyurethane, improve silk fibroin and urethane the Nomenclature Composition and Structure of Complexes and ratio thereof, and carry out manufacture craft and improve, develop a kind of new bio-medical material.The silk fibroin that the present invention synthesizes/urethane composite aquogel artificial nucleus replenishes and has developed the result of study of injecting type artificial nucleus, and synthetic silk fibroin/urethane composite aquogel has important practical medical value, and result of study will promote the development of injecting type artificial nucleus.
Comprehensive, the silk fibroin of preparation method's preparation of the present invention/urethane composite aquogel has good suitability with human body; Can realize the Replacement of injecting type artificial nucleus, postoperative effective, lasting stability.
Embodiment
The present invention is described in further detail below in conjunction with embodiment, and following examples are explanation of the invention and the present invention is not limited to following examples.
Embodiment 1:
Present embodiment has been described the preparation method of a kind of silk fibroin/urethane composite aquogel.
Under the nitrogen protection condition, be that the molecular weight of 2000 polypropylene glycol, 12.00g is that 2000 polyoxyethylene glycol adds in the there-necked flask with the molecular weight of the isophorone diisocyanate of 13.30g and 18.00g, 88-95 ℃ of lower reaction 2h obtains primary product;
Isosorbide-5-Nitrae-butyleneglycol of b, the dimethylol propionic acid that adds 1.70g in primary product, 1.40g, 40 milliliters of acetone, the inferior tin of octoate catalyst react 3h under the 65-72 ℃ of condition, obtain polyurethane hydrogel;
C, take by weighing 10.00g after the silkworm silk shredded, at the Na2CO of 0.5wt%
3Boil in the aqueous solution and removed silk gum in 40-60 minute, then use the deionized water repetitive scrubbing for several times, until the surface does not have satiny sensation, obtain washing silk;
D, will wash silk and in 40 ℃ of vacuum drying ovens, place and under 40 ℃ of constant temperatures, be dissolved in the lithium bromide water solution of 9 mol/L after 24 hours, obtain silk fibroin solution;
E, be the dialysis tubing of 8000-14000 with silk fibroin solution with the molecular weight cut-off of packing into after the filter-cloth filtering, be placed in the large beaker that fills with deionized water dialysis three days, changed water one time every 12 hours in the process, obtain dialyzate;
F, dialyzate is poured in the centrifuge tube, under 6000 rpm rotating speeds, removed insoluble substance in centrifugal 10 minutes, obtain silk fibroin protein solution, be placed in 4 ℃ the refrigerator and preserve;
G, silk fibroin protein solution and the polyurethane hydrogel volume ratio according to 1:1 is mixed, obtain silk fibroin/urethane composite aquogel.
Embodiment 2:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of dimethylol propionic acid is 1.60g, and the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.10g, and the amount of acetone is 35ml.
Embodiment 3:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of dimethylol propionic acid is 1.60g, and the consumption of Isosorbide-5-Nitrae-butyleneglycol is 0.90g, and the amount of acetone is 37ml.
Embodiment 4:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.00g, and the amount of acetone is 30ml.
Embodiment 5:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of dimethylol propionic acid is 1.60g, and the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.20g, and the amount of acetone is 41ml.
Embodiment 6:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.30g, and the amount of acetone is 38ml.
Embodiment 7:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of dimethylol propionic acid is 1.60g, and the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.00g, and the amount of acetone is 36ml.
Embodiment 8:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.20g, and the amount of acetone is 31ml.
Embodiment 9:
The processing method of present embodiment is identical with embodiment 1, and difference only is, the molecular weight that with the molecular weight of 24.00g is 1000 polyoxyethylene glycol replacement 12.00g is 2000 polyoxyethylene glycol, the consumption of dimethylol propionic acid is 2.09g, the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.32g, and the amount of acetone is 37ml.
Embodiment 10:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.80g, and the amount of acetone is 30ml.
Embodiment 11:
The processing method of present embodiment is identical with embodiment 1, and difference only is, the molecular weight that with the molecular weight of 24.00g is 1000 polyoxyethylene glycol replacement 12.00g is 2000 polyoxyethylene glycol, the consumption of dimethylol propionic acid is 2.11g, the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.56g, and the amount of acetone is 41ml.
Embodiment 12:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.72g, and the amount of acetone is 38ml.
Embodiment 13:
The processing method of present embodiment is identical with embodiment 1, and difference only is, the molecular weight that with the molecular weight of 24.00g is 1000 polyoxyethylene glycol replacement 12.00g is 2000 polyoxyethylene glycol, the consumption of dimethylol propionic acid is 2.10g, the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.44g, and the amount of acetone is 36ml.
Embodiment 14:
The processing method of present embodiment is identical with embodiment 1, and difference only is that the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.49g, and the amount of acetone is 31ml.
Embodiment 15::
The processing method of present embodiment is identical with embodiment 1, difference only is, the molecular weight that with the molecular weight of 24.00g is 1000 polyoxyethylene glycol replacement 12.00g is 2000 polyoxyethylene glycol, and the consumption of dimethylol propionic acid is 2.11g, the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.80g.In the present embodiment, isocyano and hydroxyl ratio are 1.4:1.
Embodiment 16::
The processing method of present embodiment is identical with embodiment 1, difference only is, the molecular weight that with the molecular weight of 24.00g is 1000 polyoxyethylene glycol replacement 12.00g is 2000 polyoxyethylene glycol, and the consumption of dimethylol propionic acid is 2.10g, the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.53g.In the present embodiment, isocyano and hydroxyl ratio are 1.5:1.
Embodiment 16::
The processing method of present embodiment is identical with embodiment 1, difference only is, the molecular weight that with the molecular weight of 24.00g is 1000 polyoxyethylene glycol replacement 12.00g is 2000 polyoxyethylene glycol, and the consumption of dimethylol propionic acid is 2.09g, the consumption of Isosorbide-5-Nitrae-butyleneglycol is 1.32g.In the present embodiment, isocyano and hydroxyl ratio are 1.6:1.Injecting type artificial nucleus-silk fibroin/Polyurethane composite aquogel syringeability test:
Method: get one section lumbar vertebrae of an adult boar of just having butchered, soft tissue that it is adhered to is removed clean, is kept in 20 ℃ the refrigerator for subsequent use.Use surgical knife outside fiber ring before intervertebral disk to open a little otch, through nucleus pulpous cavity, its small incision diameter 3-4mm.With the nucleus pulposus spatula gelatinous nucleus pulposus is removed totally as far as possible, just synthetic silk fibroin/urethane composite aquogel is injected the nucleus pulposus cavity by syringe, avoid not the hydrogel of completely crued liquid state flows out from otch as far as possible.
Result: silk fibroin/urethane composite aquogel, can be at room temperature directly inject with liquid state or the semi-solid syringe with diameter 2mm, wound is little, fill a nucleus pulposus space with the nucleus pulposus space, be full of irregular nucleus pulposus residual cavity fully, have suitability, surface irregularity, with the close combination of fibrous ring, be difficult for deviating from.
In addition, need to prove, the specific embodiment described in this specification sheets, its prescription, title that technique is named etc. can be different.Allly conceive equivalence or the simple change that described structure, feature and principle are done according to patent of the present invention, be included in the protection domain of patent of the present invention.Those skilled in the art can make various modifications or replenish or adopt similar mode to substitute described specific embodiment; only otherwise depart from structure of the present invention or surmount this scope as defined in the claims, all should belong to protection scope of the present invention.
Although the present invention with embodiment openly as above; but it is not to limit protection scope of the present invention; any technician who is familiar with this technology not breaking away from change and the retouching of doing in the spirit and scope of the present invention, all should belong to protection scope of the present invention.
Claims (9)
1. the preparation method of silk fibroin/urethane composite aquogel, its preparation process is
A, under the nitrogen protection condition, be that 2000 polypropylene glycol adds in the there-necked flask with the molecular weight of the isophorone diisocyanate of polyoxyethylene glycol, 133 weight parts, 180 weight parts, described polyoxyethylene glycol is that the molecular weight of 120 weight parts is that the molecular weight of 2000 polyoxyethylene glycol or 240 weight parts is 1000 polyoxyethylene glycol, 88-95 ℃ of lower reaction 2h obtains primary product;
1 of b, the dimethylol propionic acid that in primary product, adds 16-17 weight part or 20.9-21.1 weight part, 9-18 weight part, 4-butyleneglycol, acetone, the inferior tin of octoate catalyst, react 3h under the 65-72 ℃ of condition, obtain polyurethane hydrogel, wherein, the amount of the inferior tin of octoate catalyst is that the isophorone diisocyanate of every 13.3g adds one;
C, take by weighing 10 g after the silkworm silk shredded, at the Na of 0.5wt%
2CO
3Boil in the aqueous solution and removed silk gum in 40-60 minute, then use the deionized water repetitive scrubbing for several times, until the surface does not have satiny sensation, obtain washing silk;
D, will wash silk and in 40 ℃ of vacuum drying ovens, place and under 40 ℃ of constant temperatures, be dissolved in the lithium bromide water solution of 9 mol/L after 24 hours, obtain silk fibroin solution;
E, be the dialysis tubing of 8000-14000 with silk fibroin solution with the molecular weight cut-off of packing into after the filter-cloth filtering, be placed in the large beaker that fills with deionized water dialysis three days, changed water one time every 12 hours in the process, obtain dialyzate;
F, dialyzate is poured in the centrifuge tube, under 6000 rpm rotating speeds, removed insoluble substance in centrifugal 10 minutes, obtain silk fibroin protein solution, be placed in 4 ℃ the refrigerator and preserve;
G, silk fibroin protein solution and the polyurethane hydrogel volume ratio according to 1:1 is mixed, obtain silk fibroin/urethane composite aquogel.
2. the preparation method of silk fibroin according to claim 1/urethane composite aquogel, it is characterized in that: in the described polyurethane hydrogel, isocyano and hydroxyl ratio are 1.4:1-1.6:1.
3. the preparation method of silk fibroin according to claim 1/urethane composite aquogel, it is characterized in that: the amount of described acetone is: in the solid matters of 50 grams, add 30-40ml.
4. the preparation method of silk fibroin according to claim 1/urethane composite aquogel is characterized in that: add the medicinal barium sulfate powder in the described step g.
5. the application of the prepared silk fibroin of the described preparation method of claim 1/urethane composite aquogel in the preparation of artificial nucleus prosthese.
6. the application of the prepared silk fibroin of the described preparation method of claim 1/urethane composite aquogel in the artificial skin preparation.
7. the application of the prepared silk fibroin of the described preparation method of claim 1/urethane composite aquogel in the preparation of human body soft tissue charges.
8. the application of the prepared silk fibroin of the described preparation method of claim 1/urethane composite aquogel in the artificial breast prosthesis preparation.
9. the prepared silk fibroin of the described preparation method of the claim 1/application of urethane composite aquogel in orthopedic injection-type charges.
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| CN104311848A (en) * | 2014-09-25 | 2015-01-28 | 苏州印丝特纺织数码科技有限公司 | Preparation method of regenerated fibroin-nano titanium oxide composite membrane |
| CN105169476B (en) * | 2015-09-15 | 2018-06-22 | 王岩松 | A kind of preparation method and applications of medical situ-gel |
| CN107913434A (en) * | 2017-11-21 | 2018-04-17 | 深圳大学 | A kind of preparation method of aerogel dressing |
| CN109929124B (en) * | 2017-12-15 | 2021-06-18 | 天津大学 | Body temperature stimulation shape memory hydrogel for hemangioma embolism and preparation method and application thereof |
| CN108794771B (en) * | 2018-06-25 | 2020-06-02 | 华中科技大学 | Double-network cross-linked cellulose/silk fibroin high-strength hydrogel and preparation and application thereof |
| CN112384569B (en) * | 2018-07-06 | 2023-04-11 | 株式会社普利司通 | Soft polyurethane foam, automobile seat cushion, and process for producing soft polyurethane foam |
| CN110483727A (en) * | 2019-08-21 | 2019-11-22 | 大连海事大学 | A kind of polyurethane hydrogel and preparation method thereof and coating application |
| CN113713178B (en) * | 2021-08-31 | 2023-03-24 | 山东百多安医疗器械股份有限公司 | Regeneration promoting and displacement preventing artificial nucleus prosthesis and preparation method thereof |
| CN114989622B (en) * | 2022-07-15 | 2023-03-03 | 西南大学 | Isocyanate/silk fibroin composite film and preparation method thereof |
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