CN101234217B - Functional targeting therapeutic degradable biological bracket and use thereof - Google Patents
Functional targeting therapeutic degradable biological bracket and use thereof Download PDFInfo
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- CN101234217B CN101234217B CN 200810101484 CN200810101484A CN101234217B CN 101234217 B CN101234217 B CN 101234217B CN 200810101484 CN200810101484 CN 200810101484 CN 200810101484 A CN200810101484 A CN 200810101484A CN 101234217 B CN101234217 B CN 101234217B
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Abstract
The invention provides a degradable multi-functional bio-scaffold with good mechanical elasticity and supporting property, which can make target therapy for wounds; a novel material which can be biologically degraded is adopted as a scaffold matrix and is synthesized through a polymer structural design, and the novel material has good mechanical property and adjustable degradable performance, and specific drugs or radioactive materials are loaded on the matrix to cause the scaffold to provide mechanical support as well as slowly releasing drugs and making radioactive therapy for lesion locations such as stenosis, obstruction and tumors, etc., after the scaffold is implanted into human lumen.
Description
Technical field
The present invention relates to a kind of functional targeting therapeutic degradable biological bracket, particularly a kind of novel biodegradable material synthetic by high molecular structural design is as the matrix of support, appendix certain drug or radioactive substance on matrix, make after support implant into body tube chamber when providing mechanics to support to narrow, block, the lesions position slow releasing pharmaceutical such as tumor and carry out radiation treatment.This multi-functional degraded support with comprehensive therapy can be applicable to Wicresoft's interventional therapy clinical medicine domain, for the human organ tube chamber narrow, block or tumor plays remarkable and positive therapeutic effect.
Background technology
Along with the raising of people's living standard and the change of living habit and diet structure, digestive system disease, cardiovascular and cerebrovascular disease etc. is just presenting the trend of rising, and toward becoming younger development.Each organ tube chamber of digestive tract, cardiovascular and cerebrovascular vessel narrow or to block be the common complication of digestive system, blood circulation diseases, be divided into optimum and malignant stricture or block two classes.Traditional Drug therapy and surgical operation therapy effect are limited, and implant frame becomes a kind of effective minimally-invasive treatment technology in development in recent years, it is a kind of quick, the effective and comparatively safe medical procedure for the treatment of digestive tract, cardiovascular and cerebrovascular vessel benign and malignant stenosis or obstruction, do not control or the disease of refractory has been opened up new treatment approach for traditional operation, improved existence time limit and the quality of life of tumor patient.
Current widely used support is mainly metal and alloy bracket thereof from the angle of material, is secondly plastic rubber bracket.Although these widely used supports have played effective effect clinically, also exist problems, such as implanting rear constant pain, there is long term complication, treating again ratio height etc.In addition, metal rack is not because degrading, be difficult to again take out, finally as a kind of foreign body, retain for a long time in body, can cause gastral chronic injury, in the course of time easily cause the atrophy of internal layer muscle, aneurysmal formation and reactive neointimal hyperplasia, even cause digestive tract and arterial vascular restenosis.So stricter to the restriction ratio of metal rack indication clinically, only limit in general malignant tumor, there is the expert advice metal rack should classify taboo as for benign stricture.So, in fact just affected this treatment means of inner support scope of application clinically.In addition, metal rack is very expensive, is applicable to estimating that survival period is the tumor patient more than 3 months or economic condition permission person so main.
The biological degradability support can decompose in vivo after certain treatment cycle finishes, and has exempted the misery of again taking out, and for the digestive tract benign stricture and for the acute obstruction relief of symptoms, in order to choosing date for operation, provides a good clinical solution.
Studying at present and using many degraded macromolecular materials is mainly polylactide (polylactic acid), PGA and copolymer thereof, by the polylactic acid-based material of different structure, different performance of having selected different comonomer people to obtain.But polylactic acid is synthetic more difficult, and the molecular weight of product that the direct polymerization method obtains is not high enough, and the two step synthesis complex process adds that cost of material is higher, causes the cost of polylactic acid very high, has limited it and has applied widely.
The research of China's inner support is started late, and innovating to some extent aspect processing technology, configuration improvement except some support, quite a few only belongs to the imitation imported product, from material, is mainly nondegradable metal, plastic rubber bracket.
The inventor thinks from the biodegradation support of the own intellectual property of height development of design of material, to make China occupy leader status at worldwide interventional therapy Material Field, not only there is very large medical value, and there is positive social meaning, huge market prospect.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, a kind of degradable is provided and there is good mechanics retractility and supportive, and the biological support that can be treated wound surface.This support can be widely used in tube chamber in human organ narrow, block and the treatment of tumor.
The technical conceive of the innovation invention is, utilize the means such as high molecular polymerization, copolymerization, blend that Polyalkylcyanoacrylanano is prepared into to the porous substrate with excellent mechanical performances for basic degradable polymer material, on porous substrate, the medicines such as recombination line rhzomorph D (dactinomycin), paclitaxel, paclitaxel derivant (as taxotere), 5-Fluorouracil, rapamycin, 5-Fu are suppressed tumor, simultaneously appendix radioelement on porous substrate
99tc
m,
192ir,
125i carries out radiotherapy to tumor, has opened up new treatment approach, has improved existence time limit and the quality of life of tumor patient.
Technical scheme of the present invention is as follows:
Functional targeting therapeutic degradable biological bracket, comprise the base material with degradability and good mechanical property, and on base material compound antitumor drug layer and radioelement layer, it is characterized in that: the surface of support is also carried and has been covered control slow release putting material to control the rate of release of antitumor drug.
Described degradability biological support base material be homopolymer with Polyalkylcyanoacrylanano of good biocompatibility and degradability, copolymer and with the blend of other conventional degradable high polymer materials.The chemical constitution expression way of Polyalkylcyanoacrylanano is as follows:
Wherein, R
1, R
2, R
3, R
4can be different respectively various organic substituents, can be also part or all of identical organic substituent.For each substituent group, known their the various isomers of those skilled in the art also ought to have been comprised.
The sequential structure of Polyalkylcyanoacrylanano macromolecular chain, can be homopolymer (the n=0 while p=0 of alkyl cyanoacrylate class monomer, or m=0 while p=0), can be also the copolymer (p=0) of two or more alkyl cyanoacrylate class monomer, can also be the copolymer (p ≠ 0) of one or more alkyl cyanoacrylate class monomers and alkyl acrylate ester monomer.
Described biodegradable timbering material, have good solubility property and melting behaviour, thereby be easy to be processed into different configurations according to the construction features of each organ tube chamber of digestive system, blood circulation and urinary system.
Described antitumor drug layer is line rhzomorph D (dactinomycin), paclitaxel, paclitaxel derivant (as taxotere), 5-Fluorouracil, rapamycin, 5-Fu or other antitumorigenic substance.Described radiotherapy material is
99tc
m,
192ir,
125i or other radioactive element.Antitumor drug and radiotherapy material pass through the mode appendix of chemical bonding or physically trapping in the inside of porous support materials.
Described support base material has good physical and mechanical property, radial support power >=5N, and maximum radial support force≤28N, the support of diameter >=20mm can be compressed to diameter between 6-9mm; Diameter can be compressed between diameter 2.5-6mm at the support of 10-20mm.
The degradation rate of described timbering material can carry out accuracy controlling by the micro structure of macromolecular chain and the mesoscopic structure of material, and degradation cycle can be selected arbitrarily between three months to 2 years.
The catabolite of described timbering material Polyalkylcyanoacrylanano is water miscible paracyanogen base acrylic acid, and it is not stored in tissue, can from urine, excrete.Polyalkylcyanoacrylanano copolymer and blend thereof, along with the degraded of Polyalkylcyanoacrylanano composition, disintegrate finally reaches the degraded to integral material to its material.
Technique effect of the present invention is as follows:
When a kind of functional targeting therapeutic degradable biological bracket provides mechanics to support to the tube chamber of human lesion organ, can also carry out the medicine chemotherapy and radiation to primary affection, the hypertrophy and even the tube chamber restenosis that effectively suppress inner membrance and fibrous tissue, improved existence time limit and the quality of life of tumor patient.
The accompanying drawing explanation
The structural representation that Fig. 1 is functional targeting therapeutic degradable biological bracket of the present invention, wherein A section means the enlarged drawing of support section structure.
Fig. 2 is the outline drawing for esophagostenosis or the degradable biological support that blocks.
Fig. 3 is the outline drawing for duodenal stenosis or the degradable biological support that blocks.
Fig. 4 is the outline drawing of or the degradable biological support that block narrow for arteries.
The electron scanning micrograph of the medicine-carried nano particles that Fig. 5 is particle diameter 220nm.
The electron scanning micrograph of the medicine-carried nano particles that Fig. 6 is particle diameter 105nm.
The electron micrograph in the timbering material cross section that Fig. 7 is the appendix medicine-carried nano particles
Reference numeral is as follows:
1. multiporous biological support base material, 2. suppress the tumour medicine layer, and 3. radioactive substance, 4. control slow release and put clad.
Specific implementation method
The present invention relates to a kind of functional targeting therapeutic degradable biological bracket and uses thereof, be specifically related to:
1. functional targeting therapeutic degradable biological support, the degradability porous substrate that comprises support, suppress medicine layer, the slow releasing layer of radiochemotherapy layer and control, it is characterized in that: loaded tumor suppression medicine and radioactive element in the space of described degradability porous substrate, go back appendix on its surface the control slow release put the mesoporous nano material, having formed one has mechanic properties and has both narrow simultaneously, block and tumor suppresses to repair and the function of chemotherapy radiotherapy treatment, wherein, the homopolymer that described degradability porous substrate is polybutylcyanoacrylate, copolymer and blend thereof, the polymer chain structure of described polybutylcyanoacrylate is the homopolymer of cyanoacrylate monomer, or the copolymer of two or more cyanoacrylate monomer, or the copolymer of one or more cyanoacrylate monomers and acrylate monomer.
2. according to the described functional targeting therapeutic degradable biological of paragraph 1 support, it is characterized in that: the molecular weight of described polybutylcyanoacrylate homopolymer and copolymer thereof is controlled at 1,000～10 according to the requirement of the mechanical property to timbering material and degradation property is different, between 000,000.
3. according to the described functional targeting therapeutic degradable biological of paragraph 1 support, it is characterized in that: described polybutylcyanoacrylate copolymer, comprise different alkyl chain lengths, copolymerization between the cyanoacrylate monomer of different performance, also comprise the copolymerization between cyanoacrylate monomer and various unsaturated monomer, described unsaturated monomer is selected from: acrylic acid, methacrylic acid, acrylic acid methyl ester., methyl methacrylate, ethyl acrylate, butyl acrylate, styrene, maleic anhydride, vinylacetate, hydroxyethyl methylacrylate, vinyl pyrrolidone, the degradation material of described polybutylcyanoacrylate, the blend that has simultaneously also comprised polybutylcyanoacrylate homopolymer and copolymer and other macromolecular materials, described other macromolecular materials are selected from: polyacrylic acid, polymethylacrylic acid, polymethyl acrylate, polymethyl methacrylate, polyethyl acrylate, butyl polyacrylate, polystyrene, polyvinyl acetate, poly hydroxy ethyl acrylate, polyvinyl pyrrolidone, the degradation material of described polybutylcyanoacrylate also comprises the blend that alpha-cyanoacrylate ester homopolymer and copolymer and other degradable materials form, and these materials are selected from: the synthesized degradable macromolecular material, the natural degradable macromolecular material, and natural degradable inorganic material.
4. according to the described functional targeting therapeutic degradable biological of paragraph 3 support, it is characterized in that: described synthesized degradable macromolecular material is selected from polylactic acid, polyglycolic acid, polylactic acid/hydroxy acetate multipolymer, poe, polyamino acid.
5. according to the described functional targeting therapeutic degradable biological of paragraph 3 support, it is characterized in that: described natural degradable macromolecular material is selected from collagen protein, gelatin, agar, glucosan, chitosan, hyaluronic acid.
6. according to the described functional targeting therapeutic degradable biological of paragraph 3 support, it is characterized in that: described natural degradable inorganic material is selected from hydroxyapatite, calcium phosphate and Corallium Japonicum Kishinouye.
7. according to the described functional targeting therapeutic degradable biological of paragraph 1 support, it is characterized in that: described biodegradable timbering material, there is good solubility property and melting behaviour, be processed into different configurations according to the construction features of each organ tube chamber of digestive system, blood circulation and urinary system, there is good mechanical mechanics property, for Esophageal Stent, its radial support power >=5N, support can tightly be attached at lumen wall and give the mechanics support that narrow positions is enough, prevents displacement and slippage; Its maximum radial support force≤28N, to cause the damage of local lumen wall after avoiding support to discharge and to be embedded in tube wall the reparation reaction that causes that surrounding tissue is excessive, cause neointimal hyperplasia, or cause the aneurysm of local vascular simultaneously; The support compression diameter of diameter >=20mm is to 6-9mm; Diameter at the support compression diameter of 10-20mm to 2.5-6mm.
8. according to the described functional targeting therapeutic degradable biological of paragraph 1 support, it is characterized in that: described Biodegradable stents, its degradation rate can carry out accuracy controlling by the micro structure of macromolecular chain and the mesoscopic structure of material, and degradation cycle was selected arbitrarily between three months to 2 years.
9. according to the described functional targeting therapeutic degradable biological of paragraph 1 support, it is characterized in that: described inhibition medicine layer is for being used for the treatment of tube chamber restenosis and anti-tumor drug, and medicine is selected from: line rhzomorph D (dactinomycin), paclitaxel, paclitaxel derivant, 5-Fluorouracil, rapamycin, 5-Fu.
10. according to the described functional targeting therapeutic degradable biological of paragraph 9 support, it is characterized in that, described paclitaxel derivant is taxotere.
11. according to the described functional targeting therapeutic degradable biological of paragraph 1 support, it is characterized in that: described radiochemotherapy layer is radioelement
99tc
m,
192ir,
125i, by causing surface grafting polymerization, will be incorporated into the macromolecular chain of functional groups the surface of timbering material, form one deck " polymer brush ", and the above-mentioned radioelement of chelating is realized the located irradiation treatment to tumor locus.
12. according to the described functional targeting therapeutic degradable biological of paragraph 1 support, it is characterized in that: the mesoporous material that the slow releasing layer of described control is silica system, under solutions of weak acidity, the pore former of some is dissolved in water-ethanol mixed solvent, with positive esters of silicon acis, mix homogeneously, backflow heating hydrolysis certain hour under stirring, be cooled to room temperature standing, then by the gel fragmentation, soak and stir with deionized water, so washing is 6～8 times, by carrying the support that has covered inhibition medicine and radioelement, by dip-coating method, make colloidal sol be compound in the surface of support, carry out again after lyophilization by firm attachment in rack surface, form the slow releasing layer of control, the slow releasing layer pore-size distribution D of control
50≤ 15nm, drug loading is controlled and is no less than 1%, and entrapment efficiency is no less than 30%.
13., according to the described functional targeting therapeutic degradable biological of paragraph 12 support, it is characterized in that: releasing layer pore-size distribution D is delayed in described control
50≤ 5nm.
14., according to the described functional targeting therapeutic degradable biological of paragraph 12 support, it is characterized in that: releasing layer pore-size distribution D is delayed in described control
50in scope in 5～15nm.
15. preparing the various due to illness organ luminal stenosis that change causes in human body and the purposes in blocking the medicine of being treated according to the described functional targeting therapeutic degradable biological of paragraph 1-11 any one support.
16. according to the described purposes of paragraph 15, it is characterized in that the organ luminal stenosis that described organ luminal stenosis and blocking causes for tumor and blocking.
17. according to the described purposes of paragraph 15 or 16, it is characterized in that, described organ is selected from: food 6 roads of digestive system, Stomach duodenum, small intestinal, colon, rectum, bile duct, ductus pancreaticus, the tremulous pulse of blood circulation, vein, heart, each organ of urinary system and reproductive system, eyes cornea, lachrymal gland, skin.
Below in conjunction with accompanying drawing, the present invention is described in further detail.
The base material Polyalkylcyanoacrylanano homopolymer of functional targeting therapeutic degradable biological bracket and the synthesis technique of copolymer thereof, undertaken by radical polymerization as well known to those skilled in the art or anionic polymerisation.Concrete polymerization comprises polymerisation in bulk, polymerisation in solution, suspension polymerisation, emulsion polymerisation, micro-emulsion polymerization, inverse emulsion polymerization, dispersin polymerization etc.Preferred emulsion polymerization of the present invention, its major advantage is to obtain very high polymer molecular weight (factor that makes speed improve in other polymerizations often makes molecular weight reduce) when improving rate of polymerization.The viscosity of emulsion and polymer molecular weight and polymer content relation are little in addition, and system viscosity is little, is conducive to mass-and heat-transfer.
The base material of functional targeting therapeutic degradable biological bracket, except homopolymer and the copolymer thereof of the above Polyalkylcyanoacrylanano, also comprised the blend of Polyalkylcyanoacrylanano homopolymer and copolymer and common high molecular materials.They comprise: polyacrylic acid, polymethylacrylic acid, polymethyl acrylate, polymethyl methacrylate, polyethyl acrylate, butyl polyacrylate, polystyrene, polyvinyl acetate, poly hydroxy ethyl acrylate, polyvinyl pyrrolidone, and other have the macromolecular compound of monomer polymerizations formation of similar unsaturation.Polyalkylcyanoacrylanano homopolymer and copolymer thereof can also form mechanical property and the degradation property of blend to improve material with some known degradable materials, these known degradation materials are polylactic acid, polyglycolic acid, the synthesized degradable macromolecular materials such as polylactic acid/hydroxy acetate multipolymer, poe, polyamino acid, the natural degradable macromolecular materials such as collagen protein, gelatin, agar, glucosan, chitosan, hyaluronic acid, and the natural degradable inorganic material such as hydroxyapatite, calcium phosphate and Corallium Japonicum Kishinouye.
Functional targeting therapeutic degradable biological bracket, its structure forms as shown in Figure 1, wherein A section means the enlarged drawing of support section structure, comprise the porous substrate 1 with degradability and good mechanical property, and on porous substrate compound antitumor drug layer 2 and radioelement layer 3, in addition, the surface of support is also carried and has been covered control slow release putting material 4 to control the rate of release of antitumor drug.
The functional targeting therapeutic degradable biological bracket material, there is good solubility property and melting behaviour, can be processed into different configurations according to the construction features of each organ tube chambers such as digestive system, blood circulation and urinary system, be illustrated in figure 2 the outline drawing for esophagostenosis or the degradable biological support that blocks, Fig. 3 is the outline drawing for duodenal stenosis or the degradable biological support that blocks, and Fig. 4 is the outline drawing of or the degradable biological support that block narrow for arteries.
The appendix of the antitumor drug layer of functional targeting therapeutic degradable biological bracket is to be loaded in the space of base material by immersion, lyophilization, antitumor drug is line rhzomorph D (dactinomycin), paclitaxel, paclitaxel derivant (as taxotere), 5-Fluorouracil, rapamycin, 5-Fu, etc.The homopolymer of Polyalkylcyanoacrylanano and copolymer, contain numerous cyano functional group (C ≡ N) on its macromolecular chain, its reactivity is very high, thereby can make according to actual needs cyano group that a series of subsequent reactions occur, derives easily many other functional groups.Such as, can obtain carboxyl (COOH) by hydrolysis, carboxyl under weak basic condition (as ammonia, NH
3h
2o) can be converted into amide group (CONH
2), then pass through Huffman (hoffman) degraded and can change amido (NH into again
2), utilize this series of subsequent reactions can obtain some needed functional groups, obtain a kind of functional surface, then with this, carry out the various medicines of bonding.
Functional targeting therapeutic degradable biological bracket antineoplastic radioelement comprises
99tc
m,
192ir,
125i etc., the surface grafting polymerization caused by ultraviolet light, plasma etc., will be incorporated into the macromolecular chain of functional groups the surface of timbering material, form one deck " polymer brush ".By the above-mentioned radioelement of these functional group chelatings, can realize the located irradiation treatment to tumor.
In order to increase the appendix amount of material to chemotherapeutics and radioelement, improve the surface chemical composition of material, can also improve the space topological structure of material surface on meso-scale by various process meanses, as size, quantity and the distribution etc. of surperficial degree of roughness, hole.Preferred template method of the present invention, because the formed bore hole size of template and shape determine by template, select and make suitable template and just can accurately control the size and dimension of hole.
The present invention prepares mesoporous nano medicine carrying particle by simple and effective dispersion polymerization process and sol-gel process, in the extensive yardstick of the large I of these particles between 10nm-5 μ m, regulate continuously, and particle diameter is very even, approach monodispersity, as shown in Figure 5, the diameter of the mesoporous nano medicine carrying particle of preparation is 220nm, and as shown in Figure 6, the diameter of the mesoporous nano medicine carrying particle of preparation is 105nm.The mesoporous nano material of high-ratio surface is as the chemotherapeutics of all kinds of target tumor sensitivities of pharmaceutical carrier appendix, utilize the chemotherapeutics of the mesoporous nano material of above-mentioned high-ratio surface as all kinds of target tumor sensitivities of pharmaceutical carrier appendix, utilize above-mentioned reaction kinetic that medicament-carried nano mesoporous material appendix is formed to coating on the support matrix, as shown in Figure 7, obtain functional targeting therapeutic degradable biological bracket.
Present technique is compared with the prior art:
The Biodegradable high molecular support of Polyalkylcyanoacrylanano homopolymer, copolymer and blend compared to the prior art, has following outstanding advantages:
(1) good biocompatibility of timbering material, degradable, safe, nontoxic;
(2) synthesis technique of Polyalkylcyanoacrylanano homopolymer and copolymer thereof is simple, meets the development trend of environmental protection and " Green Chemistry ";
(3) the microcosmic materials chemistry structure designability of Polyalkylcyanoacrylanano homopolymer and copolymer thereof is strong, by the micro structure to its macromolecular chain, effectively regulates, and can conveniently obtain the support of different mechanical properties, different degradation rates;
(4) integrate the treatment function of mechanics support and radiotherapy chemotherapy.
It should be pointed out that the above specific embodiment can make the invention of those skilled in the art's comprehend the innovation, but limit never in any form the innovation invention.Therefore, although this description is with reference to drawings and Examples, to the innovation, invention has been described in detail,, it will be appreciated by those skilled in the art that still and can modify or be equal to replacement this utility model; And all do not break away from technical scheme and the improvement thereof of the spirit and scope of the innovation invention, it all should be encompassed in the middle of the protection domain of the innovation patent of invention.
Claims (17)
1. functional targeting therapeutic degradable biological support, the degradability porous substrate that comprises support, suppress medicine layer, the slow releasing layer of radiochemotherapy layer and control, it is characterized in that: loaded tumor suppression medicine and radioactive element in the space of described degradability porous substrate, go back appendix on its surface the control slow release put the mesoporous nano material, having formed one has mechanic properties and has both narrow simultaneously, block and tumor suppresses to repair and the function of chemotherapy radiotherapy treatment, wherein, the homopolymer that described degradability porous substrate is polybutylcyanoacrylate, copolymer and blend thereof, the polymer chain structure of described polybutylcyanoacrylate is the homopolymer of cyanoacrylate monomer, or the copolymer of two or more cyanoacrylate monomer, or the copolymer of one or more cyanoacrylate monomers and acrylate monomer.
2. functional targeting therapeutic degradable biological support according to claim 1, it is characterized in that: the molecular weight of described polybutylcyanoacrylate homopolymer and copolymer thereof, be controlled at 1 according to the requirement of the mechanical property to timbering material and degradation property is different, 000～10, between 000,000.
3. functional targeting therapeutic degradable biological support according to claim 1, it is characterized in that: described polybutylcyanoacrylate copolymer, comprise different alkyl chain lengths, copolymerization between the cyanoacrylate monomer of different performance, also comprise the copolymerization between cyanoacrylate monomer and various unsaturated monomer, described unsaturated monomer is selected from: acrylic acid, methacrylic acid, acrylic acid methyl ester., methyl methacrylate, ethyl acrylate, butyl acrylate, styrene, maleic anhydride, vinylacetate, hydroxyethyl methylacrylate, vinyl pyrrolidone, the degradation material of described polybutylcyanoacrylate, the blend that has simultaneously also comprised polybutylcyanoacrylate homopolymer and copolymer and other macromolecular materials, described other macromolecular materials are selected from: polyacrylic acid, polymethylacrylic acid, polymethyl acrylate, polymethyl methacrylate, polyethyl acrylate, butyl polyacrylate, polystyrene, polyvinyl acetate, poly hydroxy ethyl acrylate, polyvinyl pyrrolidone, the degradation material of described polybutylcyanoacrylate also comprises the blend that alpha-cyanoacrylate ester homopolymer and copolymer and other degradable materials form, and these materials are selected from: the synthesized degradable macromolecular material, the natural degradable macromolecular material, and natural degradable inorganic material.
4. functional targeting therapeutic degradable biological support according to claim 3, it is characterized in that: described synthesized degradable macromolecular material is selected from polylactic acid, polyglycolic acid, polylactic acid/hydroxy acetate multipolymer, poe, polyamino acid.
5. functional targeting therapeutic degradable biological support according to claim 3, it is characterized in that: described natural degradable macromolecular material is selected from collagen protein, gelatin, agar, glucosan, chitosan, hyaluronic acid.
6. functional targeting therapeutic degradable biological support according to claim 3, it is characterized in that: described natural degradable inorganic material is selected from hydroxyapatite, calcium phosphate and Corallium Japonicum Kishinouye.
7. functional targeting therapeutic degradable biological support according to claim 1, it is characterized in that: described biodegradable timbering material, there is good solubility property and melting behaviour, be processed into different configurations according to the construction features of each organ tube chamber of digestive system, blood circulation and urinary system, there is good mechanical mechanics property, for Esophageal Stent, its radial support power >=5N, support can tightly be attached at lumen wall and give the mechanics support that narrow positions is enough, prevents displacement and slippage; Its maximum radial support force≤28N, to cause the damage of local lumen wall after avoiding support to discharge and to be embedded in tube wall the reparation reaction that causes that surrounding tissue is excessive, cause neointimal hyperplasia, or cause the aneurysm of local vascular simultaneously; The support compression diameter of diameter >=20mm is to 6-9mm; Diameter at the support compression diameter of 10-20mm to 2.5-6mm.
8. functional targeting therapeutic degradable biological support according to claim 1, it is characterized in that: described Biodegradable stents, its degradation rate can carry out accuracy controlling by the micro structure of macromolecular chain and the mesoscopic structure of material, and degradation cycle was selected arbitrarily between three months to 2 years.
9. functional targeting therapeutic degradable biological support according to claim 1, it is characterized in that: described inhibition medicine layer is for being used for the treatment of tube chamber restenosis and anti-tumor drug, and medicine is selected from: line rhzomorph D (dactinomycin), paclitaxel, paclitaxel derivant, 5-Fluorouracil, rapamycin, 5-Fu.
10. functional targeting therapeutic degradable biological support according to claim 9, is characterized in that, described paclitaxel derivant is taxotere.
11. functional targeting therapeutic degradable biological support according to claim 1 is characterized in that: described radiochemotherapy layer is radioelement
99tc
m,
192ir,
125i, by causing surface grafting polymerization, will be incorporated into the macromolecular chain of functional groups the surface of timbering material, form one deck " polymer brush ", and the above-mentioned radioelement of chelating is realized the located irradiation treatment to tumor locus.
12. functional targeting therapeutic degradable biological support according to claim 1, it is characterized in that: the mesoporous material that the slow releasing layer of described control is silica system, under solutions of weak acidity, the pore former of some is dissolved in water-ethanol mixed solvent, with positive esters of silicon acis, mix homogeneously, backflow heating hydrolysis certain hour under stirring, be cooled to room temperature standing, then by the gel fragmentation, soak and stir with deionized water, so washing is 6～8 times, by carrying the support that has covered inhibition medicine and radioelement, by dip-coating method, make colloidal sol be compound in the surface of support, carry out again after lyophilization by firm attachment in rack surface, form the slow releasing layer of control, the slow releasing layer pore-size distribution D of control
50≤ 15nm, drug loading is controlled and is no less than 1%, and entrapment efficiency is no less than 30%.
13. functional targeting therapeutic degradable biological support according to claim 12 is characterized in that: releasing layer pore-size distribution D is delayed in described control
50≤ 5nm.
14. functional targeting therapeutic degradable biological support according to claim 12 is characterized in that: releasing layer pore-size distribution D is delayed in described control
50in scope in 5～15nm.
15. preparing the various due to illness organ luminal stenosis that change causes in human body and the purposes in blocking the medicine of being treated according to the described functional targeting therapeutic degradable biological of claim 1-11 any one support.
16. purposes according to claim 15, is characterized in that, the organ luminal stenosis that described organ luminal stenosis and blocking causes for tumor and blocking.
17. according to the described purposes of claim 15 or 16, it is characterized in that, described organ is selected from: the esophagus of digestive system, Stomach duodenum, small intestinal, colon, rectum, bile duct, ductus pancreaticus, the tremulous pulse of blood circulation, vein, heart, each organ of urinary system and reproductive system, eyes cornea, lachrymal gland, skin.
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| CN111544170B (en) * | 2020-05-13 | 2021-12-10 | 东华大学 | Anti-slip narrow-resistance esophageal stent with mesoporous structure |
| CN114082000B (en) * | 2021-12-08 | 2022-07-29 | 深圳市儿童医院 | Biodegradable drug-loaded high polymer material stent and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1391886A (en) * | 2002-08-01 | 2003-01-22 | 复旦大学 | Medicine releasing control method for implanting type medical equipment |
| WO2003094990A1 (en) * | 2002-05-09 | 2003-11-20 | Hemoteq Gmbh | Compounds and method for coating surfaces in a haemocompatible manner |
| WO2005082434A2 (en) * | 2004-02-28 | 2005-09-09 | Hemoteq Gmbh | Biocompatible coating, method, and use of medical surfaces |
| CN1806857A (en) * | 2005-01-17 | 2006-07-26 | 李庆范 | Multilayer-coated stent for controlled drug release and manufacturing method thereof |
| CN1857742A (en) * | 2005-04-30 | 2006-11-08 | 中国科学院金属研究所 | Biomedicine implant material with controllable degrading rate and its application |
-
2008
- 2008-03-07 CN CN 200810101484 patent/CN101234217B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003094990A1 (en) * | 2002-05-09 | 2003-11-20 | Hemoteq Gmbh | Compounds and method for coating surfaces in a haemocompatible manner |
| CN1391886A (en) * | 2002-08-01 | 2003-01-22 | 复旦大学 | Medicine releasing control method for implanting type medical equipment |
| WO2005082434A2 (en) * | 2004-02-28 | 2005-09-09 | Hemoteq Gmbh | Biocompatible coating, method, and use of medical surfaces |
| CN1806857A (en) * | 2005-01-17 | 2006-07-26 | 李庆范 | Multilayer-coated stent for controlled drug release and manufacturing method thereof |
| CN1857742A (en) * | 2005-04-30 | 2006-11-08 | 中国科学院金属研究所 | Biomedicine implant material with controllable degrading rate and its application |
Non-Patent Citations (2)
| Title |
|---|
| Keiichi Yoshida et al.Thin Sol-Gel-Derived Silica Coatings on Dental Pure Titanium Casting.《Journal of Biomedical Materials Research》.1999,第48卷(第6期),第778-785页. |
| Thin Sol-Gel-Derived Silica Coatings on Dental Pure Titanium Casting;Keiichi Yoshida et al;《Journal of Biomedical Materials Research》;19991205;第48卷(第6期);第779页左栏第3段 * |
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