44results about How to "Has a nanoscale structure" patented technology

The invention discloses a hollow type magnetic nanoparticle contrast agent. The microsphere has a hollow inorganic / organic / inorganic three layer structure, a cavity is located in the center of the microsphere and is filled with air; the inner layer is Fe3O4 magnetic particles; the intermediate layer is core-shell polymer nanoparticles obtained by free radical copolymerization of polyacrylic acid-divinyl benzene, and the copolymer and the Fe3O4 magnetic particle in the inner layer form stable coordination bonds or ionic bonds through inner surface carboxyl group and ferric salt; and the outer layer is silicon dioxide, and the carboxyl group on the surface of microspheres and silicon hydroxyl on silica surface are connected through hydrogen-bond interaction. The material has the advantages that the polymer microsphere belongs to the nanometer particle, the inner Fe3O4 magnetic particles enable the contrast agent to target, the silica hollow microspheres have good biological compatibility and the mechanical stability, and internal cavity can produce strong echo signal in contrast mode.

The present invention discloses self-assembled targeted nanometer drug carrier micelles. The self-assembled targeted nanometer drug carrier micelle preparation method comprises: adopting an atom transfer radical polymerization method to polymerize phosphatidyl choline to obtain poly phosphatidyl choline; modifying the poly phosphatidyl choline with folic acid molecules; adopting a ring-opening polymerization method to polymerize S-benzyl-L-cysteine carboxylic anhydride to obtain poly S-benzyl-L-cysteine; grafting adriamycin on the poly S-benzyl-L-cysteine through a hydrazone bond; bonding the poly phosphatidyl choline and the poly S-benzyl-L-cysteine through a click chemistry method to obtain a block copolymer; respectively dissolving the block polymer in tetrahydrofuran, transferring into a dialysis bag, carrying out dialysis with purified water, and filtering the dialyzed solution with a filtration membrane; and carrying out freeze-drying on the filtered solution to obtain the drug-loaded micelles, wherein the drug carrier micelles have a core-shell double-layer structure, the outer layer is the hydrophilic poly phosphatidyl choline, and the inner layer is the drug molecule wrapping layer. According to the present invention, the material has the following advantages that: the material belongs to the nanoparticles; the targeted drug delivery on the cancer cells and the pH-sensitive drug release in the cancer cells can be achieved; the drug loading is high; the stability is good; and with the targeting function, the toxic-side effect of the drug on the normal tissues and organs can be effectively reduced.

The invention discloses a polymer magnetic particle composite ultrasonic imaging microsphere. The microsphere has a hollow inorganic / organic / inorganic three-layer structure, wherein a cavity is formed in the center of the microsphere and is filled with air inside; Fe3O4 magnetic particles are formed on the outer layer of the cavity; an intermediate layer is formed by a core / shell polymer nano microsphere obtained through free radical copolymerization of a poly(isopropyl acrylamide)-polymethylacrylic acid random copolymer, polymethylacrylic acid and divinyl benzene; coordinate bonds or ionic bonds can be formed between the copolymer and the Fe3O4 magnetic particles on the inner layer of the copolymer via carboxyl on the inner surface of the microsphere and iron salt, so that the microsphere is stable; an outer layer is formed by silicon dioxide and is connected with the intermediate layer through hydrogen-bond intersection between carboxyl on the surface of the microsphere and silicon hydroxyl on the surface of silicon dioxide. The material has the advantages that the polymer microsphere belongs to nanoparticles; a contrast agent can achieve targeted localization via the Fe3O4 magnetic particles on the inner layer; the silicon dioxide hollow microsphere has good biocompatibility and mechanical stability, and the inside cavity can generate strong echo signals in a contrast mode.

The invention discloses a preparation method of a medical polymer drug. The preparation method comprises the following steps: polymerizing acrylic acid by utilizing an atom transfer radical polymerization method, thus obtaining polyacrylic acid; modifying polyacrylic acid by utilizing folic acid molecules; polymerizing aspartic acid benzyl ester carboxylic acid anhydride by utilizing a ring opening polymerization method, thus obtaining polyaspartic acid benzyl ester; grafting adriamycin onto polyaspartic acid benzyl ester via hydrazone bonds; connecting polyacrylic acid with polyaspartic acid benzyl ester with bonds through click chemistry, thus obtaining block copolymers; after dissolving the block copolymers in tetrahydrofuran respectively, transferring the solutions into a dialysis bag, dialyzing the solutions with pure water, and filtering the dialysate with a filter membrane; freeze-drying the solutions after filtration, thus obtaining a drug loading micelle. The drug carrier micelle has a core / shell double-layer structure, wherein the outer layer is formed by hydrophilic polyacrylic acid, and the inner layer is a drug molecule coated layer. The material has the advantages that the material belongs to nanoparticles; the drug can achieve targeting delivery of cancer cells and pH-sensitive release in the cancer cells; the material has high drug loading capacity and good stability; the toxic and side effects of the drug on normal tissues and organs can be effectively reduced via the targeting function of the drug.

The invention discloses a preparation method of an adriamycin polymer drug. The method comprises the following steps: polymerizing acrylamide by utilizing an atom transfer radical polymerization method to obtain polyacrylamide; modifying the polyacrylamide by utilizing folic acid molecules; polymerizing glutamic acid-benzyl ester-carboxylic acid anhydride by utilizing a ring opening polymerization method to obtain poly (benzyl glutamate); grafting the poly (benzyl glutamate) with adriamycin by hydrazone bond; carrying out bond connection between the polyacrylamide and the poly (benzyl glutamate) by a click chemical method to obtain a block copolymer; dissolving the block copolymer respectively in tetrahydrofuran, and then moving into a dialysis bag to dialyze by using pure water, and filtering dialysate by using a filter membrane; performing freeze drying to a filtered solution to obtain micelle loading medicine. The micelle loading the medicine has a core-shell bilayer structure, wherein the outer layer is hydrophilic polyacrylamide, and the inner layer is a wrapper of pharmaceutical molecules. The adriamycin polymer drug has the following advantages of belonging to nanoparticles; being capable of realizing targeted delivery of the medicine for cancerous cells and pH sensitivity releasing in the cancerous cells; large drug loading capacity; good stability; effectively reducing toxic and side effects of the medicine on normal tissues and organs by virtue of the targeted delivery function.

The invention discloses a polymer nano drug microcapsule containing polypyrrolidone. A preparation method of the polymer nano drug microcapsule comprises the following steps: polymerizing pyrrolidone by utilizing an atom transfer radical polymerization method, thus obtaining polypyrrolidone; modifying polypyrrolidone by utilizing folic acid molecules; polymerizing glutamic acid octadecylester carboxylic acid anhydride by utilizing a ring opening polymerization method, thus obtaining polyglutamic acid octadecylester; grafting adriamycin onto polyglutamic acid octadecylester via hydrazone bonds; connecting polypyrrolidone with polyglutamic acid with bonds through click chemistry, thus obtaining block copolymers; after dissolving the block copolymers in tetrahydrofuran respectively, transferring the solutions into a dialysis bag, dialyzing the solutions with pure water, and filtering the dialysate with a filter membrane; freeze-drying the solutions after filtration, thus obtaining a drug loading micelle. The drug carrier micelle has a core / shell double-layer structure, wherein the outer layer is formed by hydrophilic polypyrrolidone, and the inner layer is a drug molecule coated layer. The material has the advantages that the material belongs to nanoparticles; the polymer nano drug microcapsule can achieve targeting delivery of drug to cancer cells and pH-sensitive release of the drug in the cancer cells; the material has high drug loading capacity and good stability; the toxic and side effects of the drug on normal tissues and organs can be effectively reduced via the targeting function of the drug.

The invention discloses a self-assembled drug carrier microcapsule system containing polyacrylic acid. A preparation method of the system comprises the following steps: polymerizing acrylic acid by utilizing an atom transfer radical polymerization method, thus obtaining polyacrylic acid; modifying polyacrylic acid by utilizing folic acid molecules; polymerizing O-benzyl-L-tyrosine carboxylic acid anhydride by utilizing a ring opening polymerization method, thus obtaining poly(O-benzyl-L-tyrosine); grafting adriamycin onto poly(O-benzyl-L-tyrosine) via hydrazone bonds; connecting polyacrylic acid with poly(O-benzyl-L-tyrosine) with bonds through click chemistry, thus obtaining block copolymers; after dissolving the block copolymers in tetrahydrofuran respectively, transferring the solutions into a dialysis bag, dialyzing the solutions with pure water, and filtering the dialysate with a filter membrane; freeze-drying the solutions after filtration, thus obtaining a drug loading micelle. The drug carrier micelle has a core / shell double-layer structure, wherein the outer layer is formed by hydrophilic polyacrylic acid, and the inner layer is a drug molecule coated layer. The material has the advantages that the material belongs to nanoparticles; the drug can achieve targeting delivery of cancer cells and pH-sensitive release in the cancer cells; the material has high drug loading capacity and good stability; the toxic and side effects of the drug on normal tissues and organs can be effectively reduced via the targeting function of the drug.

The present invention discloses a novel magnetic ferric oxide hollow microsphere contrast agent. According to the present invention, the microsphere has a hollow inorganic / organic / inorganic three-layer structure, the cavity is positioned in the center of the microsphere, air is filled in the internal, the outer layer of the cavity is alpha-Fe2O3 magnetic particles, the middle layer is core / shell polymer nanometer microspheres obtained by carrying out free radical copolymerization on a polyacrylonitrile-polyacrylic acid random copolymer, polyacrylic acid and divinylbenzene, the carboxyl on the inner surface and the iron salt can form the coordination bond or ion bond so as to provide the stability between the copolymer and the alpha-Fe2O3 magnetic particles in the inner layer, the outer layer is silicon dioxide, and the carboxyl on the microsphere surface and the silanol on the silicon dioxide surface produce the hydrogen bond effect so as to connect; and the magnetic ferric oxide composite medical contrast agent has the following advantages that: the polymer microspheres belong to the nanoscale particles, the contrast agent can provide the targeting positioning function with the alpha-Fe2O3 magnetic particles in the inner layer, the silicon dioxide hollow microsphere has good biocompatibility and good mechanical stability, and the internal cavity can produce the strong echo signal under the contrasting mode.

The invention discloses a preparation method of a high-molecular-based pH-sensitive medicament micelle. Phosphatidylcholine is subjected to an atom transfer radical polymerization reaction to obtain poly phosphatidylcholine. Benzyl glutamate carboxylic acid anhydride is subjected to a ring-opening polymerization reaction to obtain poly(benzyl glutamate) ester. The poly(benzyl glutamate) ester is grafted to doxorubicin through a hydrazone bond. The poly phosphatidylcholine is bonded to the poly(benzyl glutamate) ester in a manner of click chemistry to obtain a block copolymer. The block copolymer is respectively dissolved in tetrahydrofuran to obtain a solution. The solution is transferred to a dialysis bag for carrying out a dialysis process through pure water to obtain a dialysate which is filtered through a filter membrane. A freeze drying process is carried out to the filtered solution to obtain a medicant carrier micelle. The drug carrier micelle has a core-shell double-layer structure with an external layer being hydrophilic poly phosphatidylcholine and an internal layer being medicament molecule wrapping layer. The drug carrier micelle has advantages of belonging to nano particles and enabling a targeting transmission of a drug to cancer cells and a pH-sensitive releasing process in the cancer cells to be achieved. The drug carrier micelle is large in drug carrying capacity and good in stability. A targeting function of the drug carrier micelle can effectively reduce toxic and side effects of drugs on normal tissues and organs.

The invention discloses a medical ultrasonic diagnosis contrast agent hollow composite microsphere system. The microsphere has a hollow inorganic / organic / inorganic three-layer structure, wherein a cavity is formed in the center of the microsphere and is filled with air inside; Fe3O4 magnetic particles are formed on the outer layer of the cavity; an intermediate layer is formed by a core / shell polymer nano microsphere obtained through free radical copolymerization of a polybutylene-polymethylacrylic acid random copolymer, polymethylacrylic acid and divinyl benzene; coordinate bonds or ionic bonds can be formed between the copolymer and the Fe3O4 magnetic particles on the inner layer of the copolymer via carboxyl on the inner surface of the microsphere and iron salt, so that the microsphere is stable; an outer layer is formed by silicon dioxide and is connected with the intermediate layer through hydrogen-bond intersection between carboxyl on the surface of the microsphere and silicon hydroxyl on the surface of silicon dioxide. The material has the advantages that the polymer microsphere belongs to nanoparticles; the contrast agent can achieve targeted localization via the Fe3O4 magnetic particles on the inner layer; the silicon dioxide hollow microsphere has good biocompatibility and mechanical stability, and the inside cavity can generate strong echo signals in a contrast mode.

The invention discloses a polymer ultrasonic imaging contrast agent containing unsaturated bonds. A microsphere has a hollow inorganic / organic / inorganic three-layer structure, wherein a cavity is formed in the center of the microsphere and is filled with air inside; Fe3O4 magnetic particles are formed on the outer layer of the cavity; an intermediate layer is formed by a core / shell polymer nano microsphere obtained through free radical copolymerization of a polybutadiene-polyacrylic acid random copolymer, polyacrylic acid and divinyl benzene; coordinate bonds or ionic bonds can be formed between the copolymer and the Fe3O4 magnetic particles on the inner layer of the copolymer via carboxyl on the inner surface of the microsphere and iron salt, so that the microsphere is stable; an outer layer is formed by silicon dioxide and is connected with the intermediate layer through hydrogen-bond intersection between carboxyl on the surface of the microsphere and silicon hydroxyl on the surface of silicon dioxide. The material has the advantages that the polymer microsphere belongs to nanoparticles; the contrast agent can achieve targeted localization via the Fe3O4 magnetic particles on the inner layer; the silicon dioxide hollow microsphere has good biocompatibility and mechanical stability, and the inside cavity can generate strong echo signals in a contrast mode.

The present invention discloses a magnetic ferric oxide composite medical contrast agent. According to the present invention, the microsphere has a hollow inorganic / organic / inorganic three-layer structure, the cavity is positioned in the center of the microsphere, the internal is filled with air, the outer layer of the cavity is alpha-Fe2O3 magnetic particles, the middle layer is core / shell polymer nanometer microspheres obtained by carrying out free radical copolymerization on a poly(methyl acrylate)-polyacrylic acid random copolymer, polyacrylic acid and divinylbenzene, the carboxyl on the inner surface and the iron salt can form the coordination bond or ion bond so as to provide the stability between the copolymer and the alpha-Fe2O3 magnetic particles in the inner layer, the outer layer is silicon dioxide, and the carboxyl on the microsphere surface and the silanol on the silicon dioxide surface produce the hydrogen bond effect so as to realize connection; and the magnetic ferric oxide composite medical contrast agent has the following advantages that: the polymer microspheres belong to the nanoscale particles, the contrast agent can provide the targeting positioning function with the alpha-Fe2O3 magnetic particles in the inner layer, the silicon dioxide hollow microsphere has good biocompatibility and good mechanical stability, and the internal cavity can produce the strong echo signal under the contrasting mode.

The invention discloses a method for preparing a pH sensitive drug carrier micelle. The method comprises the steps of: polymerizing phosphatidylcholine by using an atomic transfer radical polymerization method to obtain poly phosphatidylcholine; modifying the poly phosphatidylcholine by folate molecules; polymerizing benzyl glutamate carboxyanhydride by using a ring opening polymerization method to obtain poly(gamma-benzyl-L-glutamate); grafting adriamycin to poly(gamma-benzyl-L-glutamate) through a hydrazone bond; bonding the poly phosphatidylcholine and poly(gamma-benzyl-L-glutamate) via a click chemical method to obtain a block copolymer; respectively dissolving the block copolymer in tetrahydrofuran, transferring into a dialysis bag, and dialyzing by pure water, and filtering the dialysate by a dialysis membrane; and conducting freeze drying on the filtered solution, so as to obtain get the drug carrier micelle. The drug carrier micelle has a core-shell double-layer structure; and the outer layer is hydrophilic poly phosphatidylcholine, and the inner layer is a molecular drug coating. The material has the following advantages: the micelle belongs to nano particles, can realize targeting delivery of drug to cancer cells and pH sensitive release in cancer cell, and has large drug loading capacity and good stability; and the targeting function can effectively reduce the toxic and side effect of drugs on normal tissue and organs..

The invention discloses a nano magnetic microspheric ultrasound imaging contrast medium. A microsphere is in a hollow inorganic / organic / inorganic three-layer structure. A hollow cavity is formed in the center of the microsphere with air therein. A Fe3O4 magnetic particle is formed on an external layer of the hollow cavity. A middle layer is a core / shell polymer nano-microsphere which is formed from a polyethylene-polyacrylic acid random copolymer and polyacrylic acid and divinyl benzene through free radical polymerization. A coordinate bond or an ionic bond can be formed between the copolymer and the Fe3O4 magnetic particle, in the internal layer, through carboxyl groups and ferric salts on an internal surface so that the structure is stable. An external layer is silicon dioxide which is connected to the nano-microsphere through a hydrogen bond effect due to the carboxyl groups on the nano-microsphere and silicon hydroxyl groups on the surface of the silicon dioxide. The system is advantaged in that the polymer microsphere belongs to nano-scale particles, wherein the Fe3O4 magnetic particle in the internal layer allows targeted positioning of the contrast medium, the silicon dioxide hollow microsphere is good in biocompatibility and mechanical-stability, and the hollow cavity can generate a strong echo signal under a radiography mode.

The invention discloses a preparation method of a tumor cell micro-environmentally responsive nano-micelle. The preparation method comprises the following steps: polymerizing pyrrolidone by utilizing an atom transfer radical polymerization method, thus obtaining polypyrrolidone; modifying polypyrrolidone by utilizing folic acid molecules; polymerizing O-tert-butyl-L-threonine carboxylic acid anhydride by utilizing a ring opening polymerization method, thus obtaining poly(O-tert-butyl-L-threonine); grafting adriamycin onto poly(O-tert-butyl-L-threonine) via hydrazone bonds; connecting polypyrrolidone with poly(O-tert-butyl-L-threonine) with bonds through click chemistry, thus obtaining block copolymers; after dissolving the block copolymers in tetrahydrofuran respectively, transferring the solutions into a dialysis bag, dialyzing the solutions with pure water, and filtering the dialysate with a filter membrane; freeze-drying the solutions after filtration, thus obtaining a drug loading micelle. The drug carrier micelle has a core / shell double-layer structure, wherein the outer layer is formed by hydrophilic polypyrrolidone, and the inner layer is a drug molecule coated layer. The material has the advantages that the material belongs to nanoparticles; the drug can achieve targeting delivery of cancer cells and pH-sensitive release in the cancer cells; the material has high drug loading capacity and good stability; the toxic and side effects of the drug on normal tissues and organs can be effectively reduced via the targeting function of the drug.

The invention discloses a nano self-assembly drug carrier microcapsule system which is prepared through following steps: (1) polymerizing phosphatidylcholine through an atom transfer radical polymerization method to obtain poly-phosphatidylcholine; (2) modifying the poly-phosphatidylcholine with a folic acid molecule; (3) polymerizing O-benzyl-L-tyrosine carboxylic acid anhydride through a ring-opening polymerization method to obtain poly-O-benzyl-L-tyrosine; (4) performing stem-grafting to the poly-O-benzyl-L-tyrosine with adriamycin through a hydrazone bond; (5) performing a bond-connecting process to the poly-phosphatidylcholine and the poly-O-benzyl-L-tyrosine in a click chemical manner to obtain a segmented copolymer; (6) dissolving the segmented copolymer in tetrahydrofuran and moving the solution to a dialysis bag, performing dialysis with pure water, and filtering a dialyzate through a filter membrane; and (7) freeze-drying a solution after filtration to obtain a medicine carrying micelle. The medicine carrying micelle has a double-layer core-shell structure of which an outer layer is hydrophilic poly-phosphatidylcholine and an inner layer is a drug molecule wrapping layer. The microcapsule belongs to nano-particles, can achieve targeted transmission of the drug and pH-sensitive releasing in cancer cells, is large in drug carrying amount and is good in stability. The targeted function can reduce toxic and side effects of the drug on normal tissue and organ.

The invention discloses a preparation method of a biocompatible polymer antitumor drug. The preparation method comprises the following steps: polymerizing pyrrolidone by utilizing an atom transfer radical polymerization method, thus obtaining polypyrrolidone; modifying polypyrrolidone by utilizing folic acid molecules; polymerizing aspartic acid benzyl ester carboxylic acid anhydride by utilizing a ring opening polymerization method, thus obtaining polyaspartic acid benzyl ester; grafting adriamycin onto polyaspartic acid benzyl ester via hydrazone bonds; connecting polypyrrolidone with polyaspartic acid benzyl ester with bonds through click chemistry, thus obtaining block copolymers; after dissolving the block copolymers in tetrahydrofuran respectively, transferring the solutions into a dialysis bag, dialyzing the solutions with pure water, and filtering the dialysate with a filter membrane; freeze-drying the solutions after filtration, thus obtaining a drug loading micelle. The drug carrier micelle has a core / shell double-layer structure, wherein the outer layer is formed by hydrophilic polypyrrolidone, and the inner layer is a drug molecule coated layer. The material has the advantages that the material belongs to nanoparticles; the drug can achieve targeting delivery to cancer cells and pH-sensitive release in the cancer cells; the material has high drug loading capacity and good stability; the toxic and side effects of the drug on normal tissues and organs can be effectively reduced via the targeting function of the drug.

The invention discloses a composite hollow-type medical contrast medium system. A microsphere is in a hollow inorganic / organic / inorganic three-layer structure. A hollow cavity is formed in the center of the microsphere with air therein. A Fe3O4 magnetic particle is formed on an external layer of the hollow cavity. A middle layer is a core / shell polymer nano-microsphere which is formed from a polypropylene-polymethylacrylic acid random copolymer and polymethylacrylic acid and divinyl benzene through free radical polymerization. A coordinate bond or an ionic bond can be formed between the copolymer and the Fe3O4 magnetic particle, in the internal layer, through carboxyl groups and ferric salts on an internal surface so that the structure is stable. An external layer is silicon dioxide which is connected to the nano-microsphere through a hydrogen bond effect due to the carboxyl groups on the nano-microsphere and silicon hydroxyl groups on the surface of the silicon dioxide. The system is advantaged in that the polymer microsphere belongs to nano-scale particles, wherein the Fe3O4 magnetic particle in the internal layer allows targeted positioning of the contrast medium, the silicon dioxide hollow microsphere is good in biocompatibility and mechanical-stability, and the hollow cavity can generate a strong echo signal under a radiography mode.

The invention discloses a targeted amphipathic nano-drug microcapsule which is prepared through following steps: (1) polymerizing phosphatidylcholine through an atom transfer radical polymerization method to obtain poly-phosphatidylcholine; (2) modifying the poly-phosphatidylcholine with a folic acid molecule; (3) polymerizing octadecyl glutamate carboxylic acid anhydride through a ring-opening polymerization method to obtain poly-octadecyl glutamate; (4) performing stem-grafting to the poly-octadecyl glutamate with adriamycin through a hydrazone bond; (5) performing a bond-connecting process to the poly-phosphatidylcholine and the poly-octadecyl glutamate in a click chemical manner to obtain a segmented copolymer; (6) dissolving the segmented copolymer in tetrahydrofuran and moving the solution to a dialysis bag, performing dialysis with pure water, and filtering a dialyzate through a filter membrane; and (7) freeze-drying a solution after filtration to obtain a medicine carrying micelle. The medicine carrying micelle has a double-layer core-shell structure of which an outer layer is hydrophilic poly-phosphatidylcholine and an inner layer is a drug molecule wrapping layer. The microcapsule belongs to nano-particles, can achieve targeted transmission of the drug and pH-sensitive releasing in cancer cells, is large in drug carrying amount and is good in stability. The targeted function can reduce toxic and side effects of the drug on normal tissue and organ.

The present invention discloses a polymethacrylic acid-containing macromolecule drug microcapsule. The preparation method comprises: adopting an atom transfer radical polymerization method to polymerize methacrylic acid to obtain polymethacrylic acid; modifying the polymethacrylic acid with folic acid molecules; adopting a ring-opening polymerization method to polymerize glutamic acid stearyl ester carboxylic anhydride to obtain poly glutamic acid stearyl ester; grafting adriamycin on the poly glutamic acid stearyl ester; bonding the polymethacrylic acid and the poly glutamic acid through a click chemistry method to obtain a block copolymer; respectively dissolving the block polymer in tetrahydrofuran, transferring into a dialysis bag, carrying out dialysis with purified water, and filtering the dialyzed solution with a filtration membrane; and carrying out freeze-drying on the filtered solution to obtain the drug-loaded micelles, wherein the drug carrier micelles have a core-shell double-layer structure, the outer layer is the hydrophilic polymethacrylic acid, and the inner layer is the drug molecule wrapping layer. According to the present invention, the material has the following advantages that: the material belongs to the nanoparticles; the targeted drug delivery on the cancer cells and the pH-sensitive drug release in the cancer cells can be achieved; the drug loading is high; the stability is good; and with the targeting function, the toxic-side effect of the drug on the normal tissues and organs can be effectively reduced.

The present invention discloses a polymethacrylic acid-containing self-assembled drug carrier microcapsule system. The preparation method comprises: adopting an atom transfer radical polymerization method to polymerize methacrylic acid to obtain polymethacrylic acid; modifying the polymethacrylic acid with folic acid molecules; adopting a ring-opening polymerization method to polymerize O-benzyl-L-tyrosine carboxylic anhydride to obtain poly O-benzyl-L-tyrosine; grafting adriamycin on the poly O-benzyl-L-tyrosine; bonding the polymethacrylic acid and the poly O-benzyl-L-tyrosine through a click chemistry method to obtain a block copolymer; respectively dissolving the block polymer in tetrahydrofuran, transferring into a dialysis bag, carrying out dialysis with purified water, and filtering the dialyzed solution with a filtration membrane; and carrying out freeze-drying on the filtered solution to obtain the drug-loaded micelles, wherein the drug carrier micelles have a core-shell double-layer structure, the outer layer is the hydrophilic polymethacrylic acid, and the inner layer is the drug molecule wrapping layer. According to the present invention, the material has the following advantages that: the material belongs to the nanoparticles; the targeted drug delivery on the cancer cells and the pH-sensitive drug release in the cancer cells can be achieved; the drug loading is high; the stability is good; and with the targeting function, the toxic-side effect of the drug on the normal tissues and organs can be effectively reduced.

The invention discloses a polypyrrolidone polymer drug carrier micelle. A preparation method of the polypyrrolidone polymer drug carrier micelle comprises the following steps: polymerizing pyrrolidone by utilizing an atom transfer radical polymerization method, thus obtaining polypyrrolidone; modifying polypyrrolidone by utilizing folic acid molecules; polymerizing S-benzyl-L-cysteine carboxylic acid anhydride by utilizing a ring opening polymerization method, thus obtaining poly(S-benzyl-L-cysteine); grafting adriamycin onto poly(S-benzyl-L-cysteine) via hydrazone bonds; connecting polypyrrolidone with poly(S-benzyl-L-cysteine) with bonds through click chemistry, thus obtaining block copolymers; after dissolving the block copolymers in tetrahydrofuran respectively, transferring the solutions into a dialysis bag, dialyzing the solutions with pure water, and filtering the dialysate with a filter membrane; freeze-drying the solutions after filtration, thus obtaining a drug-loading micelle. The drug carrier micelle has a core / shell double-layer structure, wherein the outer layer is formed by hydrophilic polypyrrolidone, and the inner layer is a drug molecule coated layer. The material has the advantages that the material belongs to nanoparticles; the drug can achieve targeting delivery to cancer cells and pH-sensitive release in the cancer cells; the material has high drug loading capacity and good stability; the toxic and side effects of the drug on normal tissues and organs can be effectively reduced via the targeting function of the drug.

The present invention discloses an organic-inorganic composite ultrasonic imaging microsphere preparation method. According to the present invention, the microsphere has a hollow inorganic / organic / inorganic three-layer structure, the cavity is positioned in the center of the microsphere, air is filled in the internal, the outer layer of the cavity is alpha-Fe2O3 magnetic particles, the middle layer is core / shell polymer nanometer microspheres obtained by carrying out free radical copolymerization on a polymethyl methacrylate-polyacrylic acid random copolymer, polyacrylic acid and divinylbenzene, the carboxyl on the inner surface and the iron salt can form the coordination bond or ion bond so as to provide the stability between the copolymer and the alpha-Fe2O3 magnetic particles in the inner layer, the outer layer is silicon dioxide, and the carboxyl on the microsphere surface and the silanol on the silicon dioxide surface produce the hydrogen bond effect so as to connect; and the magnetic ferric oxide composite medical contrast agent has the following advantages that: the polymer microspheres belong to the nanoscale particles, the contrast agent can provide the targeting positioning function with the alpha-Fe2O3 magnetic particles in the inner layer, the silicon dioxide hollow microsphere has good biocompatibility and good mechanical stability, and the internal cavity can produce the strong echo signal under the contrasting mode.

The invention discloses a preparation method of a magnetic ultrasonic imaging microsphere containing polybutadiene. The microsphere has a hollow inorganic / organic / inorganic three-layer structure, wherein a cavity is formed in the center of the microsphere and is filled with air inside; Fe3O4 magnetic particles are formed on the outer layer of the cavity; an intermediate layer is formed by a core / shell polymer nano microsphere obtained through free radical copolymerization of a polybutadiene-polymethylacrylic acid random copolymer, polymethylacrylic acid and divinyl benzene; coordinate bonds or ionic bonds can be formed between the copolymer and the Fe3O4 magnetic particles on the inner layer of the copolymer via carboxyl on the inner surface of the microsphere and iron salt, so that the microsphere is stable; an outer layer is formed by silicon dioxide and is connected with the intermediate layer through hydrogen-bond intersection between carboxyl on the surface of the microsphere and silicon hydroxyl on the surface of silicon dioxide. The material has the advantages that the polymer microsphere belongs to nanoparticles; a contrast agent can achieve targeted localization via the Fe3O4 magnetic particles on the inner layer; the silicon dioxide hollow microsphere has good biocompatibility and mechanical stability, and the inside cavity can generate strong echo signals in a contrast mode.

The invention discloses a preparation method of a biocompatible polymer drug. Pyrrolidone is subjected to an atom transfer radical polymerization reaction to obtain poly pyrrolidone. Benzyl aspartate carboxylic acid anhydride is subjected to a ring-opening polymerization reaction to obtain poly(benzyl aspartate) ester. The poly(benzyl aspartate) ester is grafted to doxorubicin through a hydrazone bond. The poly pyrrolidone is bonded to the poly(benzyl aspartate) ester in a manner of click chemistry to obtain a block copolymer. The block copolymer is respectively dissolved in tetrahydrofuran to obtain a solution. The solution is transferred to a dialysis bag for carrying out a dialysis process through pure water to obtain a dialysate which is filtered through a filter membrane. A freeze drying process is carried out to the filtered solution to obtain a drug carrier micelle. The drug carrier micelle has a core-shell double-layer structure with an external layer being hydrophilic polypyrrolidone and an internal layer being drug molecule wrapping layer. The drug carrier micelle has advantages of belonging to nano particles and enabling a targeting transmission of a drug to cancer cells and a pH-sensitive releasing process in the cancer cells to be achieved. The drug carrier micelle is large in drug carrying capacity and good in stability. A targeting function of the drug carrier micelle can effectively reduce toxic and side effects of drugs on normal tissues and organs.

The invention discloses a biocompatible polymer ultrasonic imaging contrast agent. A microsphere has a hollow inorganic / organic / inorganic three-layer structure, wherein a cavity is formed in the center of the microsphere and is filled with air inside; Fe3O4 magnetic particles are formed on the outer layer of the cavity; an intermediate layer is formed by a core / shell polymer nano microsphere obtained through free radical copolymerization of a polypyrrolidone-polyacrylic acid random copolymer, polyacrylic acid and divinyl benzene; coordinate bonds or ionic bonds can be formed between the copolymer and the Fe3O4 magnetic particles on the inner layer of the copolymer via carboxyl on the inner surface of the microsphere and iron salt, so that the microsphere is stable; an outer layer is formed by silicon dioxide and is connected with the intermediate layer through hydrogen-bond intersection between carboxyl on the surface of the microsphere and silicon hydroxyl on the surface of silicon dioxide. The material has the advantages that the polymer microsphere belongs to nanoparticles; the contrast agent can achieve targeted localization via the Fe3O4 magnetic particles on the inner layer; the silicon dioxide hollow microsphere has good biocompatibility and mechanical stability, and the inside cavity can generate strong echo signals in a contrast mode.

The present invention discloses an anticancer macromolecule drug preparation method, which comprises: adopting an atom transfer radical polymerization method to polymerize methacrylic acid to obtain polymethacrylic acid; modifying the polymethacrylic acid with folic acid molecules; adopting a ring-opening polymerization method to polymerize aspartic acid benzyl ester carboxylic anhydride to obtain poly aspartic acid benzyl ester; grafting adriamycin on the poly aspartic acid benzyl ester; bonding the polymethacrylic acid and the poly aspartic acid benzyl ester through a click chemistry method to obtain a block copolymer; respectively dissolving the block polymer in tetrahydrofuran, transferring into a dialysis bag, carrying out dialysis with purified water, and filtering the dialyzed solution with a filtration membrane; and carrying out freeze-drying on the filtered solution to obtain the drug-loaded micelles, wherein the drug carrier micelles have a core-shell double-layer structure, the outer layer is the hydrophilic polymethacrylic acid, and the inner layer is the drug molecule wrapping layer. According to the present invention, the material has the following advantages that: the material belongs to the nanoparticles; the targeted drug delivery on the cancer cells and the pH-sensitive drug release in the cancer cells can be achieved; the drug loading is high; the stability is good; and with the targeting function, the toxic-side effect of the drug on the normal tissues and organs can be effectively reduced.

The invention relates to a doxorubicin precursor compound which can be released under photo-response, and a preparation method and an application of same. The doxorubicin precursor compound is represented as the formula (I) and has following advantages: the compound contains a photo-sensitive group, which is connected to a strong-hydrophobic group; and then with an amphiphilic polymer, polylactic acid-glycolic acid copolymer (PLGA), which has excellent biocompatibility, as a supporter, a hydrophobic photo-responding doxorubicin prodrug molecule (DOC) is embedded in a hydrophobic core of a nano-micelle, which is formed by the PLGA; under light irradiation, the hydrophobic prodrug molecule is degraded into hydrophilic doxorubicin, which is easy to escape from the nano-supporter PLGA, thus achieving the effects of the doxorubicin. The method achieves photo-controlled release of the medicine, and solves the problems of intensive toxic and side effects since the medicine cannot be released at certain time and certain points due to incomplete release and sudden release of a doxorubicin preparation in the prior art.

The present invention discloses an adriamycin-containing macromolecule drug. The preparation method comprises: adopting an atom transfer radical polymerization method to polymerize methacrylic acid to obtain polymethacrylic acid; modifying the polymethacrylic acid with folic acid molecules; adopting a ring-opening polymerization method to polymerize lysine benzyl ester carboxylic anhydride to obtain poly lysine benzyl ester; grafting adriamycin on the poly lysine benzyl ester; bonding the polymethacrylic acid and the poly lysine benzyl ester through a click chemistry method to obtain a block copolymer; respectively dissolving the block polymer in tetrahydrofuran, transferring into a dialysis bag, carrying out dialysis with purified water, and filtering the dialyzed solution with a filtration membrane; and carrying out freeze-drying on the filtered solution to obtain the drug-loaded micelles, wherein the drug carrier micelles have a core-shell double-layer structure, the outer layer is the hydrophilic polymethacrylic acid, and the inner layer is the drug molecule wrapping layer. According to the present invention, the material has the following advantages that: the material belongs to the nanoparticles; the targeted drug delivery on the cancer cells and the pH-sensitive drug release in the cancer cells can be achieved; the drug loading is high; the stability is good; and with the targeting function, the toxic-side effect of the drug on the normal tissues and organs can be effectively reduced.

The invention discloses a chlorambucil precursor compound with photo-responsive degradation effects and its preparation and application. The precursor compound has a structural formula (I). The chlorambucil precursor molecule contains a light-sensitive group and is connected to a strong hydrophobic group through the light-sensitive group. Mesoporous silica (MSNs) with good biocompatibility is usedas a carrier so that the hydrophobic light-responsive chlorambucil prodrug molecule is adsorbed in MSNs channels. Under illumination, the hydrophobic prodrug molecule can be degraded into hydrophilicchlorambucil molecules so that the hydrophilic chlorambucil molecules can escape from mesoporous silica and produce drug effects. The preparation method realizes light-controlled release of drugs andthe problem that the existing chlorambucil preparation cannot be fully released and largely released and cannot be regularly released at fixed points so that violent toxic and side effects are produced.