Background technology
Cause damage or damaged when human organ or often organize, in congenital malformation or operation, thereby lose its original function because of wound, inflammation, tumor.Therefore, being applicable to that the research and development of the adhesive of medical of various tissue repair becomes global problem, is very active field in the biomaterial research.Existing adhesive of medical can be divided into two big classes, and a class is a soft tissue adhesives, is mainly a-hydroxy acrylic acid esters fast binder and adhesive fibrin; Another kind of is hard tissue adhesive, is mainly the bone cement that traditional methyl methacrylate is a substrate and the bone cement of reactive phosphate class.
These two kinds of soft tissue adhesives of a-hydroxy acrylic acid esters fast binder and adhesive fibrin are widely used clinically, has quick-binding, advantages such as biocompatibility is better, but the weakness of soft tissue adhesives is that its mechanical strength is very poor, degradation rate can not be regulated, and can't adapt to the bonding of various different tissues.And, be unsuitable for being applied to some meticulous ophthalmologic operation owing to become the White-opalescent shape after the polymerization of a-hydroxy acrylic acid esters binding agent.
Bone cement is in the orthopedic repair process of bone, is used to fill up damaged and the fixing material of transplant, once uses Gypsum Fibrosum etc. in early days.Nineteen sixty, British Charnley[1] first polymethyl methacrylate (PMMA) is used for fixing orthopaedic implant.This class bone cement is by two phase compositions, and solid phase is the PMMA high polymer, and liquid phase is the MMA monomer, solidifies by polyreaction after the biphase mixing.The advantage of PMMA bone cement is to be easy to plastotype, and is easy to use, can be securely fixing transplant, thereby obtained in early days using widely; But the PMMA bone cement is difficult to absorb, and implanting exists as foreign body all the time, and this is the maximum deficiency that the PMMA bone cement exists; Biocompatibility is poor, can not directly combine with osseous tissue, and between can produce fibrous layer, and then causes inflammation; Mechanical strength is low, can cause the bone cement fracture, produces fragment, thereby causes loosening [2] of transplant; Strong heat release during curing (up to 110 ℃) can cause the necrosis of surrounding tissue, simultaneously, can constantly discharge poisonous monomer [3] in body fluid.Thereby people are seeking to substitute its biological activity bone renovating material always.
The calcium phosphate bone cement of biologically active (CPC) is by two or more calcium phosphate powder, add blender, the furnishing pasty state injects repairs the position, can under human internal environment and temperature, solidify voluntarily, its composition finally is converted into the hydroxyapatite similar to the human body bone structure (HAP), have excellent biological compatibility, bone conductibility and absorbability [4], therefore, CPC has replaced the PMMA bone cement of biocompatibility difference soon, become the focus of research, now be widely used in clinical.Yet as a kind of pure inorganic material, there is crisp big, shortcoming such as mechanical property is not enough, degraded is slow in CPC, makes its application be subjected to restriction to a certain degree, is mainly used in the reparation of non-bearing bone at present.Therefore, the bioactive bone cement that preparation has excellent mechanical property makes its reparation that can be used in load-bearing bone, is a focus of current bone cement research.
In order to obtain high-intensity bone cement, research at present is to be mixed with organic resin and the bone cement that forms by the biological activity inorganic powder the most widely.This class bone cement not only has higher mechanical property, and has good biological activity, thereby becomes the focus that research worker is paid close attention to.For example, a kind of novel GBC bone cement, this class bone cement is made up of PMMA resin/biological activity inorganic filler (hydroxyapatite (HAP) powder, bioactivity glass pearl or glass-ceramic powder).Compare with traditional PMMA bone cement, the GBC bone cement not only has good operability, and has good mechanical and osteoinductive; The biology performance test result shows, between animal bone and GPC bone cement, can not produce fibrous layer, then observed fibrolaminar generation between PMMA bone cement and bone, this shows that the bond strength of GPC bone cement and bone is significantly higher than corresponding PMMA bone cement.Recently, Kim etc. [9] have made up a kind of bioactive bone cement of being made up of hydroxyapatite (HAP), chitosan powder and PMMA resin (BBC), and the biocompatibility of BBC bone cement and osteoinductive also significantly are better than single PMMA bone cement.
Though effectively improved the biocompatibility of conventional P MMA bone cement and avoided the big deficiency of single calcium phosphate bone cement fragility by said method, and the compound bone cement of preparation has certain biological activity, but still have following problem:
(1) adopting PMMA is the matrix phase, can't avoid the more inherent shortcomings of PMMA, as is difficult to strong heat release, the toxic monomer of release etc. in absorption, the biological curing process.
(2) the biologic inorganic filler mainly is the artificial-synthetic hydroxyapatite who adopts through high temperature sintering, the biocompatibility of HAP and the absorbability of calcium ion can obviously reduce in high-temperature process, thereby will cause the bioactive decline of bone cement inevitably.
(3) above-mentioned compound bone cement forms bulk during molding in vivo, does not have hole.Be unfavorable for cell, tissue growth enters defect.
(4) in addition, the mechanical strength of the compound bone cement of this class awaits further to improve.
Summary of the invention
The objective of the invention is to defective at the prior art existence, a kind of adherent Biodegradable active medical tissue adhesive of different tissues that is applicable to is provided, its use is simple to operate, and the biocompatibility of material is good, has regulatable mechanical strength and degradation rate.
The present invention also aims to provide the preparation method of described binding agent.
Binding agent of the present invention comprises and is used for bonding soft tissue, three kinds of Biodegradable active medical tissue adhesives of dentistry sclerous tissues and orthopaedics sclerous tissues.Its liquid phase is a hydroxyethyl methylacrylate ring-opening polymerisation cyclic ester class (lactide for example, Acetic acid, hydroxy-, bimol. cyclic ester, caprolactone etc.) macromonomer of Xing Chenging (macromonomer), polyester (polylactic acid, poly-Acetic acid, hydroxy-, bimol. cyclic ester, polycaprolactone etc.) be the degraded unit, alcohols (Polyethylene Glycol, glycerol, polyhydroxy substances such as tetramethylolmethane) be functional group's biodegradable cross-linker (biodegradable cross-linking agent) of central block, vinylpyrrolidone (N-Vinylpyrrolidone), N, N-dimethyl-p-toluidine (N, N-Dimethyl-p-toluidine), hydroquinone (Hydroquinone) etc.; Solid phase is encapsulated natural bone powder, porogen (phosphonized chitosan, carboxymethyl chitosan, oligochitosan), benzoyl peroxide (Benzoyl peroxide) etc.
The Biodegradable active medical tissue adhesive that is used for bonding soft tissue of the present invention, form by the component of following weight:
Monomer 15~45%
Biodegradable cross-linker 20~35%
Vinylpyrrolidone 30~63%
Benzoyl peroxide 1.5%
Hydroquinone accounts for 20~75ppm of total amount
N, the N-dimethyl is to aniline 0.5%
Above-mentioned amounts of components summation except that hydroquinone is 100%;
Described monomer is hydroxyethyl methylacrylate ring-opening polymerisation ring lactide, Acetic acid, hydroxy-, bimol. cyclic ester or caprolactone monomer; Described biodegradable cross-linker is that Polyethylene Glycol, glycerol or tetramethylolmethane are functional group's biodegradable cross-linker of central block.The preparation method of this binding agent may further comprise the steps:
(1) monomer, biodegradable cross-linker are dissolved in the vinylpyrrolidone;
(2) add benzoyl peroxide and hydroquinone, obtain clear solution;
(3) with N, the N-dimethyl splashes in the clear solution aniline, mix homogeneously.
Be used for the Biodegradable active medical tissue adhesive of bonding dentistry sclerous tissues, form by the component of following percent by weight:
Monomer 25%~50%
Biodegradable cross-linker 15%~30%
Vinylpyrrolidone 20%~55%
Light trigger IRGACURE 2,959 2.0~4.0%
Said components consumption summation is 100%;
Described monomer is hydroxyethyl methylacrylate ring-opening polymerisation ring lactide, Acetic acid, hydroxy-, bimol. cyclic ester or caprolactone monomer; Described biodegradable cross-linker is that Polyethylene Glycol, glycerol or tetramethylolmethane are functional group's biodegradable cross-linker of central block.The preparation method of this binding agent is characterized in that comprising the steps:
(1) monomer, biodegradable cross-linker are dissolved in the vinylpyrrolidone;
(2) add light trigger IRGACURE 2959.
Be used for the Biodegradable active medical tissue adhesive of bonding orthopaedics sclerous tissues, form by the component of following weight:
Monomer 20%~30%
Biodegradable cross-linker 5%~10%
Vinylpyrrolidone 10%~20%
N, the N-dimethyl is to aniline 0.25%
Hydroquinone accounts for 10~35ppm of total amount
Encapsulated natural bone powder 45%
Porogen 5%
Benzoyl peroxide 1.5%;
Above-mentioned amounts of components summation except that hydroquinone is 100%;
Described monomer is hydroxyethyl methylacrylate ring-opening polymerisation ring lactide, Acetic acid, hydroxy-, bimol. cyclic ester or caprolactone monomer; Described biodegradable cross-linker is that Polyethylene Glycol, glycerol or tetramethylolmethane are functional group's biodegradable cross-linker of central block.
One or more mixture in described porogen preferably phosphoric acid chitosan, carboxymethyl chitosan, the oligochitosan.
Described encapsulated natural bone powder is the commercial goods, also can be prepared by following method: natural bone powder is added in the polyethylene glycol-lactic acid copolymer aqueous solution, and ultra-sonic dispersion filters vacuum drying.
The preparation method of this binding agent is characterized in that comprising the steps:
(1) monomer, biodegradable cross-linker are dissolved in the vinylpyrrolidone;
(2) add N, the N-dimethyl obtains clear solution to aniline and hydroquinone;
(3) with encapsulated natural bone powder, porogen and benzoyl peroxide mix and obtain mixture, and mixture is joined mix homogeneously in the clear solution that step (2) obtains.
Monomer of the present invention is hydroxyethyl methylacrylate ring-opening polymerisation cyclic ester class monomer (macromonomer), and described cyclic ester class is lactide, Acetic acid, hydroxy-, bimol. cyclic ester or caprolactone.Can utilize terminal hydroxyl in hydroxyethyl methylacrylate (HEMA) molecule cause lactide (D, L-LA), Acetic acid, hydroxy-, bimol. cyclic ester or caprolactone carry out ring-opening polymerisation, adopts body tube sealing polymerization to prepare the macromonomer of terminal double bond functionalization.
When selecting lactide for use, form the PLA-HEMA macromonomer of terminal double bond functionalization, comprise MC-3 (hydroxyethyl methylacrylate grafted polylactic acid macromonomer 3) or MC-5 (hydroxyethyl methylacrylate grafted polylactic acid macromonomer 5), its molecular formula is as follows:
Its preparation method can adopt the following step:
(1) under the room temperature with hydroxyethyl methylacrylate (HEMA) and lactide (D, L-LA) with n (HEMA)/n (D, L-LA)=1: n (n=5,10,15,20) ratio joins the ampere bottle, (consumption is D to add the inferior stannum of octoate catalyst again, the L-LA gross weight 0.03%) and polymerization inhibitor hydroquinone (consumption be HEMA monomer gross mass 0.1%), evacuation removed solvent, moisture and oxygen, sealing by fusing reaction bulb then in 6 hours;
(2) the reacting by heating bottle places 130 ℃ baking oven reaction to obtain crude product in 24 hours until the complete fusion of reactant;
(3) dissolve the crude product after-filtration fully with oxolane, filtrate is dropwise joined in a large amount of distilled water, get precipitate behind the purification, precipitate to constant weight, obtains the PLA-HEMA macromonomer through vacuum drying.
Biodegradable cross-linker of the present invention is that alcohols is functional group's biodegradable cross-linker of central block, comprises bi-vinyl biodegradable cross-linker, triethyl group type biodegradable cross-linker or tetrem fundamental mode biodegradable cross-linker.
Described bi-vinyl biodegradable cross-linker is the bi-vinyl biodegradable cross-linker of PLA-PEG-PLA (polyethylene glycol-lactic acid) triblock copolymer terminal hydroxyl with the acryloyl chloride functionalization, and its molecular formula is as follows:
Its preparation method can be taked the following step:
(1) will put into round-bottomed flask with the PLA-PEG-PLA triblock copolymer of tube sealing polymerization preparation, it is 1: 4 that the adding triethylamine makes the PLA-PEG-PLA and the ratio of the amount of substance of triethylamine, adds dichloromethane dilution and magnetic agitation again and evenly obtains prepolymer;
(2) in the amount of prepolymer species: the ratio of third rare acyl chlorides amount of substance=1: 4 adds constant pressure funnel with third rare acyl chlorides, dilute with dichloromethane, speed with 4 droplets/second splashes into pre-polymer solution reaction 6 hours with third rare acyl chlorides in ice bath then, obtains crude product in 24 hours at room temperature reaction;
(3) remove by filter in the crude product triethylamine hydrochloride precipitation, remove excessive triethylamine with 5% dilute hydrochloric acid solution washing, separatory, during the sodium bicarbonate solution of subnatant reuse 5% washed and hydrochloric acid, to pH be 6.4, leave standstill separatory.In product solution, added a certain amount of anhydrous magnesium sulfate drying 12 hours, filter; Precipitate thick product with exsiccant normal hexane, separatory, purification afterproduct vacuum drying obtains the bi-vinyl biodegradable cross-linker to constant weight.
Among the present invention, used hydroxyethyl methylacrylate contains activity hydroxy, is colourless transparent liquid, and is water-soluble, and its homopolymer has good blood compatibility, is widely used in orthopaedics and dental materials.Macromonomer with the formation of hydroxyethyl methylacrylate ring-opening polymerisation lactide, can recently control the molecular weight of macromonomer by feeding intake, promptly kept polylactic acid good mechanical performance, introduced activity double key simultaneously, forged the hydrophilic that improves poly-lactic acid material thereby be easy to introduce other chains.Two kinds of material excellent biological compatibility, biological activity and mechanical properties have been kept.
Used vinyl pyrrolidone not only monomer is water-soluble, and its homopolymer---and polyvinyl pyrrolidone is also water-soluble.Polyvinylpyrrolidone has many good physical and chemical performances, as physiological compatibility, lyotropy, film property, water solublity etc.Eyeball is had good affinity, is the common used material that is used for making contact lens.Though polyvinylpyrrolidone is not degraded, it is water-soluble, can finally excrete by the body fluid circulation in vivo, to the harmless effect of human body cell.
Used Polyethylene Glycol is a water soluble polymer, contains active hydroxyl.Molecular weight changes and can linearly control, introduce the regulatable degradable polyester fragment of molecular weight, obtain the bi-vinyl biodegradable cross-linker after the terminal hydroxyl acryloyl chloride functionalization, have regulatable hydrophilic and hydrophobic, degradation property and active terminal double bond are easy to reaction.
Used phosphonized chitosan, carboxymethyl chitosan, oligochitosan is the water-soluble natural macromolecule and has excellent biological compatibility and biological degradability, can stripping from the bone cement piece after solidifying in the body fluid environment, form hole, and the addition by porogen, granular size can be controlled size and the porosity that forms hole, help cell, organize the defect of growing into.Especially particularly phosphonized chitosan can also instruct biomineralization as the macromole masterplate in body fluid, helps forming hydroxyapatite.
The present invention also can adopt supercritical carbon dioxide extraction (SFE-CO2) technology, because this technology has low-temperature operation, does not with an organic solvent wait advantage, use this technology to remove potential major antigen composition in the nature bone, natural bone powder after the processing not only has the special biological activity of nature bone, but also can reduce the immunological rejection of material after implanting as far as possible.
The adherent Biodegradable active medical tissue adhesive of different tissues that is applicable to provided by the invention compares with existing adhesive of medical, has following advantage:
(1), still finds no degradation rate so far, the porous active bone cement that mechanical property is adjustable though the kind of present bone cement is a lot.Injectable biological degradation activity bone cement provided by the invention can satisfy the reparation of repairing soft tissue or sclerous tissues by different compositions.
(2) vinyl monomer that biodegradable cross-linker and biocompatibility are good (vinylpyridine irons the polylactic acid macromonomer of alkane ketone (NVP), hydroxyethyl methylacrylate (HEMA), terminal double bond functionalization etc.) not only can be crosslinked fast under room temperature or radiating light source (ultraviolet or blue light), and, the heat of polymerization of this network polymers is low, form transparent polymer, and have regulatable mechanical property.
(2) network polymers has regulatable degradation property, therefore can be according to being applicable to the different tissues reparation, the binding agent that allotment and cell growth rate are complementary.Network polymers can change into gradually and can dissolve under the body fluid environment or linear molecule that degradable absorbs, and catabolite finally can excrete by the metabolism of human body.
(3) bone meal of Cai Yonging (HAP) not only has the special biological activity of nature bone, and, also reduced the immunological rejection of material after implanting as far as possible.The easier body with high polymer of encapsulated natural bone powder merges, and makes inorganic phase and organic facies good mixing, reduces the two-phase interface energy.
(4) composition of biodegradable cross-linker can be regulated by the molecular weight that changes PEG degraded unit (PLA, polyglycolic acid (PGA) and both copolymer (PLGA) etc.) and the control different structure unitary length different with selection with performance (molecular weight, degradation speed, crosslinking rate etc.).
(5) adding of porogen can form the hole of size and controlled porosity at the position of repairing, and by being beneficial to the cell adhesion increment, forms newborn osseous tissue.
(5) binding agent that is used for bonding orthopaedics sclerous tissues in human body not only degradable absorb, also have the mechanical property of special biological activity of natural bone powder and network polymers excellence concurrently; And, the mechanical property of bone cement, degradation speed and hardening time can be by changing biodegradable cross-linker composition and consumption, select different vinyl monomers for use and regulate the organic/inorganic composition proportion and control, have important and practical meanings for the reparation of the damage of satisfying different tissues or defective bone (load-bearing and non-bearing bone).
Be applicable to the non-congenital open skeleton that injects bone structure in the skeletal system (as extremity, spinal column, pelvis) damaged/slit in, and make its original position healing.These open bone cavity may be that the bone that is caused by operation is damaged or damaged to the bone that skeleton causes by wound, binding agent can be used as the bone cavity implant, can degrade gradually in the bone repair process, cyclic metabolism is to external, and active component can be absorbed and be replaced by new life's osseous tissue.
The specific embodiment
Embodiment 1
With 0.22g macromonomer (MC-5), the 0.34g degradable crosslinker is dissolved in the vinylpyrrolidone monomer of 0.44g, and the hydroquinone that adds the benzoyl peroxide of 0.0075g and 30ppm obtains homogeneous, stable clear solution component A.
When the binding skin laceration, the patient earlier after thorough cleaning wound, need not anaesthetize, stop blooding, utilize that left hand is eaten, thumb distance edge of wound 0.16~0.18cm place gently by after, play a part hemostasis by compression, and can make edge of wound close up alignment.With 0.0050g N, the N-dimethyl splashes among the component A aniline, and mix homogeneously in 1min makes it wound can be covered fully it in the wound, behind 2min~3min two fingers slowly staggered form unclamp, observe wound hemorrhage again, do not have the back of splitting and cover gauze.After testing: wound 8 all post-absorption degradeds are complete, and tissue slice shows that the material biocompatibility is good.
Embodiment 2
With 0.20g macromonomer (MC-3), the 0.40g degradable crosslinker is dissolved in the vinylpyrrolidone monomer of 0.40g, adds the benzoyl peroxide of 0.0075g and 30ppm hydroquinone and mixes and obtain homogeneous, stable clear solution component A.In ophthalmologic operation, behind the little and irregular wound suture of cornea, in component A, add 0.005gN, the N-dimethyl is to aniline, and mix homogeneously in the 1mim splashes into after the stitching wound of closure fully, 2min-3min forms transparent membranoid substance, can prevent effectively that aqueous humor from spilling.
Embodiment 3
With 0.20g macromonomer (MC-5), the 0.35g degradable crosslinker is dissolved in the vinylpyrrolidone monomer of 0.45g, and the hydroquinone that adds the benzoyl peroxide of 0.0075g and 30ppm obtains homogeneous, stable clear solution.
Fixing with lying on the back after the new zealand white rabbit anesthesia, press the asepsis principle, the epigastrium median incision enters the abdominal cavity, proposes the small intestinal epimere from disconnected.Add 0.0050gN in component one solution, the N-dimethyl is to aniline, mix homogeneously in the 1min.Glued joint intestinal tube and film edge place with it, check the anastomotic stoma ne-leakage behind the 3min, send intestinal tube back to abdominal cavity, close abdomen.12 all post-absorption degradeds are complete substantially.Tissue slice shows that the material biocompatibility is good.
Embodiment 4
With 0.28g macromonomer (MC-5), the 0.18g degradable crosslinker is dissolved in the vinylpyrrolidone monomer of 0.55g, adds 0.03g light trigger IRGACURE 2959, obtains homogeneous, stable clear solution.
To suffer from the bad tissue of endosexine, tooth nest hole dental caries and remove, carefully remove the soft dentin of deep layer then with the low speed round bur,, can keep a little soft dentin at the bottom of the hole for avoiding perforation of pulp chamber.Suffer from tooth 75% ethanol disinfection, at the bottom of the nest hole, splash into a little biodegradation binding agent, use blue light illumination 3-4min, form hard and firm lid marrow layer, the top layer composite resin filling, after 16 weeks, x ray mating plate is observed and is shown, the apex of root of tooth surrounding tissue is normal, and material is degraded substantially, and dental pulp has vigor.
Embodiment 5
With 0.09g macromonomer (MC-3), the 0.22g degradable crosslinker is dissolved in the vinylpyrrolidone monomer of 0.19g, adds 0.005gN, and the N-dimethyl obtains homogeneous, stable clear solution component one to the hydroquinone of aniline and 25ppm.
Get new zealand white rabbit, male and female are not limit.After the anesthesia, damaged with tooth section electric drill (low speed bores, drips normal saline slowly) at the holostrome that bilateral mandibular bone body makes 1.2cm * 0.6mm, excise the cheek-tongue side periosteum of this scope and inferior alveolar nerve vascular bundle and the root of the tooth that involves simultaneously.With the encapsulated natural bone powder of 0.45g, the benzoyl peroxide mixing solid phase components two of 0.05g porogen (phosphonized chitosan) and 0.0075g adds component one, and mix homogeneously in the 1min injects defect with binding agent, and 5-7min fixes, sub-cage rearing.After 14 weeks, respectively scanning electron microscopic observation is carried out on the surface of material and bone in the junction of bone and material, material and tissue bond are tight, and boundary line, former damaged place is not obvious, and difficulty distinguishes material and osseous tissue, and the biocompatibility of material is better.
Embodiment 6
With 0.22g macromonomer (MC-5), the 0.09g degradable crosslinker is dissolved in the vinylpyrrolidone monomer of 0.10g, adds 0.002gN, and the N-dimethyl obtains homogeneous, stable clear solution component A to the hydroquinone of aniline and 20ppm.Get new zealand white rabbit, male and female are not limit.After the anesthesia, cause the long bone of 1.5cm damaged together with together with periosteum amputation in the lump, sew up spatium intermusculare, subcutaneous tissue and skin then with stinging vice one section ulna in 1.5-3.0cm place under the head of ulna of left side.With the encapsulated natural bone powder of 0.36g, the benzoyl peroxide mixing solid phase components B of 0.04g porogen (phosphonized chitosan) and 0.006g adds component A, and mix homogeneously in the 1min is expelled to the bone defect with the adhesive transdermal skin.Resistance is little during injection, ne-leakage.After 5-7min is fixing, sub-cage rearing.After 20 weeks, x mating plate and scanning electron microscopic observation are carried out to the surface of material and bone respectively in junction at bone and material, material conjunctive tissue place, periosteum forms well, the bone line connects, and material and tissue bond are tight, and boundary line, former damaged place is not obvious, difficulty distinguishes material and osseous tissue, and the biocompatibility of material is better.
Embodiment 7
Under the room temperature with hydroxyethyl methylacrylate (HEMA) and Acetic acid, hydroxy-, bimol. cyclic ester (GA) with n (HEMA)/n (GA)=1: n (n=5,10,15,20) ratio joins the ampere bottle, add inferior stannum of octoate catalyst (consumption be GA gross weight 0.03%) and polymerization inhibitor hydroquinone (consumption be HEMA monomer gross mass 0.1%) again, evacuation removed solvent, moisture and oxygen, sealing by fusing reaction bulb then in 6 hours; The reacting by heating bottle places 130 ℃ baking oven reaction to obtain crude product in 24 hours until the complete fusion of reactant; Dissolve the crude product after-filtration fully with oxolane, filtrate is dropwise joined in a large amount of distilled water, get precipitate behind the purification, precipitate to constant weight, obtains the PGA-HEMA macromonomer through vacuum drying.
Embodiment 8
Under the room temperature with hydroxyethyl methylacrylate (HEMA) and caprolactone (CL) with n (HEMA)/n (CL)=1: n (n=5,10,15,20) ratio joins the ampere bottle, add inferior stannum of octoate catalyst (consumption be GA gross weight 0.03%) and polymerization inhibitor hydroquinone (consumption be HEMA monomer gross mass 0.1%) again, evacuation removed solvent, moisture and oxygen, sealing by fusing reaction bulb then in 6 hours; The reacting by heating bottle places 130 ℃ baking oven reaction to obtain crude product in 24 hours until the complete fusion of reactant; Dissolve the crude product after-filtration fully with oxolane, filtrate is dropwise joined in a large amount of distilled water, get precipitate behind the purification, precipitate to constant weight, obtains the PCL-HEMA macromonomer through vacuum drying.