CN109953976A - A kind of collaboration transports, pinpoints the microcapsules of release drug therapy breast cancer - Google Patents

A kind of collaboration transports, pinpoints the microcapsules of release drug therapy breast cancer Download PDF

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Publication number
CN109953976A
CN109953976A CN201910289436.XA CN201910289436A CN109953976A CN 109953976 A CN109953976 A CN 109953976A CN 201910289436 A CN201910289436 A CN 201910289436A CN 109953976 A CN109953976 A CN 109953976A
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China
Prior art keywords
microcapsules
drug
hydrogel
pinpoints
breast cancer
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Pending
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CN201910289436.XA
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Chinese (zh)
Inventor
李丽仙
何自强
辇伟奇
穆小松
彭贵琴
杨薇
廖斌
伍青
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Chongqing University
Chongqing Tumour Institute
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Chongqing University
Chongqing Tumour Institute
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Priority to CN201910289436.XA priority Critical patent/CN109953976A/en
Publication of CN109953976A publication Critical patent/CN109953976A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

The invention discloses a kind of collaborations to transport, pinpoints the microcapsules of release drug therapy breast cancer, including hydrogel shell, drug, magnetic material and high-affinity modifier.It is applied around externally-applied magnetic field in tumor tissues, when drug is passed through with body fluid flow to tumor tissues, the microcapsules containing magnetic material are fixed and are trapped near tumor tissue cell under the action of externally-applied magnetic field.The characteristics of nearby subacidity is presented in microenvironment, temperature is often higher than normal tissue based on tumor tissues simultaneously again, when reaching its critical inversion pH and temperature by microcapsules prepared by pH- temperature Dual Sensitive type hydrogel coating medicine, the physicochemical property of hydrogel is caused to change, to discharge drug.It realizes that intelligent response master-passive target transports, pinpoints the purpose of release drug, improves curative effect of medication, and effectively reduce drug to the toxic side effect of whole body, avoid normal tissue cell damage.

Description

A kind of collaboration transports, pinpoints the microcapsules of release drug therapy breast cancer
Technical field
The present invention relates to a kind of drug delivery capsules more particularly to a kind of intelligent response passive target to transport, pinpoints release Drug nearby treats the microcapsules of breast cancer to tumor tissue cell.
Background technique
One of the main reason for cancer is serious harm human health, leads to death.Although the research about treatment of cancer Considerable progress is achieved, but at this stage, cancer is still the public health problem of most serious in the world.Treating cancer at present Means mainly include operation excision, radiation and chemotherapy etc..Operation excision is primarily adapted for use in except the malignant tumour of hematological system is (such as white Blood disease, malignant lymphoma) outside, there is no part and DISTANT METASTASES IN and the typically small early metaphase cancers of knurl, but perform the operation There are greater risks for journey；Radiotherapy is treated mainly for the radical cure of the entity tumor relatively limited to, such as nasopharyngeal carcinoma, incidence Tumour etc. is insensitive to chemotherapy, is applied alone radiotherapy that can eradicate, but there are biggish side effects for radiotherapy, while local reaction is tighter Weight, it is larger to tumor vicinity normal tissue injury；Chemotherapy is as most effective therapeutic modality, and there is also obvious drawbacks: 1. Drug delivery, release lack targeting, be easy to cause systemic distribution, injure normal tissue cell；2. drug service life compared with It is long, so that human body is generated drug resistance.Therefore, novel multifunctional tumor cell-targeting medicine-carried system is constructed, chemotherapeutics is improved To the targeting transport efficiency of cancer site, realizes that chemotherapeutics is enriched in the targeting of cancer site, effectively improve cancerous issue Drug concentration shortens chemotherapy cycles, reduces systemic toxic side effect.Meanwhile medicine-carried system is to the cladding of drug, it can be effective Improve the biocompatibility of drug, extends the circulation time of drug in vivo, improve drug effect.
In recent years, with the rapid development of material science and nanotechnology, the hair at full speed in biologic medical field is also pushed Exhibition.Nanometer medicine-carried system can realize the enrichment near tumor tissue cell by enhancing infiltration and retention effect (EPR), reach To the purpose of efficient release drug.In addition, pH- temperature Dual Sensitive profile material achieves length in nano-medicament carrier design aspect The progress of foot.Therefore, the toxic side effect of drug normal tissue cell is reduced simultaneously to improve the functioning efficiency of drug, therefore had Necessity develops a kind of intelligent response passive target and transports, pinpoints release drug to tumor tissue cell and nearby treat the micro- of breast cancer Capsule.
Summary of the invention
It is not high for the transport efficiency of drug, while there are toxic side effects for normal tissue cell, the present invention provides one Kind collaboration transports, pinpoints the microcapsules of release drug therapy breast cancer.
In order to solve the above-mentioned technical problem, present invention employs following technical solutions:
A kind of collaboration transports, pinpoints the microcapsules of release drug therapy breast cancer, including hydrogel shell, drug, magnetism Material and high-affinity modifier；The hydrogel shell is in sphere or spheroid, coating medicine inside the hydrogel shell, Magnetic material and high-affinity modifier.
Intelligent response master-passive target collaboration transports, pinpoints and treat mammary gland near release drug to tumor tissue cell The principle of the microcapsules of cancer is: when drug flows near tumor tissues in vivo with body fluid, in the effect of externally-applied magnetic field Under, the microcapsules containing magnetic material are fixed near tumor tissues.Based on pH- temperature Dual Sensitive profile material to surrounding The response that pH, temperature change are made, volume phase transition occurs for hydrogel, to discharge drug；And when surrounding pH or temperature drop to When the minimum critical transition temperature of hydrogel or even lower minimum critical transitions pH value, the hydrogel shunk restores to original Volume state.To realize that the collaboration of master-passive target transports, pinpoints and treat mammary gland near release drug to tumor tissue cell Cancer.Medicine-carried system of the invention since drug is covered by the preferable hydrogel shell body of biocompatibility, and passes through hydrogel Characteristic, realize that master-passive target of drug transports, improve targeting transport efficiency of the chemotherapeutics to cancer site, realizationization The targeting that drug is treated in cancer site is enriched with, and is effectively improved the drug concentration of cancerous issue, is shortened chemotherapy cycles, reduces systemic Toxic side effect.Meanwhile medicine-carried system contains drug, can be effectively improved the biocompatibility of drug, extends drug in body Interior circulation time improves drug effect.
As a preferred solution of the present invention, the hydrogel shell is by pH sensitive hydrogel and responsive to temperature type water Gel is combined, wherein pH sensitive hydrogel is by poly-aspartate (PASP) hydrogel, porous hemicellulose graft copolymerization Acrylamide gel and acrylate polymer are polymerized；And temperature sensitive type water gel then uses two kinds of polyethylene glycol Derivative and chitosan-mPEG and polyvinyl alcohol (PVA) are copolymerized.
As another preferred embodiment of the invention, two kinds of derivatives of the polyethylene glycol are methacrylic acid 2- (2- Methoxy ethoxy) ethyl ester (MEO2) and methacrylate (OEGMA) MA.
As an improvement of the present invention, the constituent of the drug be taxol, adriamycin, rheum emodin and what It fills in pavilion (Herceptin).
As another improvement project of the invention, the ingredient of the magnetic material is nanoscale ferroso-ferric oxide (Fe3O4), there is magnetism.
As a further improvement of the present invention, the ingredient of the high-affinity modifier is folic acid.
Compared with prior art, the present invention has the following technical effect that
1. collaboration of the invention transports, pinpoints the microcapsules of release drug therapy breast cancer, with direct intravenous injection, oral The other methods such as drug are compared, and the therapeutic efficiency of drug is significantly improved, while the secondary work of the poison for reducing drug normal tissue cell With.
2. magnetic material ferroso-ferric oxide is wrapped in hydrogel microcapsule by the present invention, using the effect of externally-applied magnetic field, The microcapsules of coating medicine and magnetic material are fixed near tumor tissues, the targeting for greatly improving drug is defeated Transport efficiency.
3. the present invention using pH- temperature Dual Sensitive type hydrogel as the shell coating medicine of microcapsules, magnetic material, High-affinity modifier, when avoiding drug and circulating in vivo, the toxic side effect of normal tissue cell.Meanwhile it is also sharp With the deformation behavior of hydrogel achieve the purpose that passive target transport, pinpoint release drug.When because micro- under externally-applied magnetic field effect When capsule is fixed near tumor tissue cell, subacidity is presented based on tumor tissues and temperature is higher than normal tissue cell Feature, pH- temperature Dual Sensitive profile material reaches its response condition, thus deformation occurs for hydrogel, discharges inside microcapsules Drug, folic acid and magnetic response material, to realize that the passive target of drug transports, pinpoints release.
4. the present invention using pH- temperature Dual Sensitive type hydrogel as the shell coating medicine of microcapsules, magnetic material, High-affinity modifier.When pH- temperature Dual Sensitive type hydrogel reaches its response condition and deformation occurs, drug, folic acid And magnetic material is released out of microcapsules.At this point, due to losing magnetic response material, thus externally-applied magnetic field pair in microcapsules Microcapsules no longer have fixed function, and microcapsules can continue to flow with body fluid.When it is reached near normal tissue cell, due to Its pH is higher than tumor tissue cell nearby and temperature is lower than near tumor tissue cell, thus pH- temperature Dual Sensitive type water-setting Glue can absorb moisture, restore again to undeformed state, realize cladding to drug, high-affinity modifier.Drug is avoided to exist Excessive concentration at normal tissue cell reduces the toxic side effect of its normal tissue cell.
5. use scope of the present invention is wide, it is applicable to transporting for different pharmaceutical, is conducive to the transport efficiency for improving drug, together When reduce drug to the toxic side effect of normal cell, there is good medical value and social benefit.
Detailed description of the invention
Fig. 1 is a kind of structural schematic diagram for cooperateing with and transporting, pinpoint the microcapsules of release drug therapy breast cancer；
Fig. 2 is that a kind of cooperate with transports, pinpoints the microcapsules for discharging drug adaptive " on-off " release near tumor tissues The mechanism of action figure of drug.
In figure, 1-hydrogel shell；2-high-affinity modifiers；3-magnetic materials；4-drugs；5-tumor tissues Cell；6-normal tissue cells；7- externally-applied magnetic field.
Specific embodiment
The present invention is described in further detail with reference to the accompanying drawings and detailed description.
As shown in Figure 1, a kind of collaboration transports, pinpoints the microcapsules of release drug therapy breast cancer, including hydrogel shell 1, drug 4, magnetic material 3 and high-affinity modifier 2.Hydrogel shell 1 is in sphere or spheroid, 1 the inside of hydrogel shell Coating medicine 4, magnetic material 3 and high-affinity modifier 2.
Hydrogel shell 1 is combined by pH sensitive hydrogel with temperature sensitive type water gel, can be simultaneously to pH and temperature Degree is responded, and has good biocompatibility, is suitable as drug delivery carrier.Wherein, pH sensitive hydrogel It is poly- by poly-aspartate (PASP) hydrogel, porous hemicellulose graft copolymerization acrylamide gel and acrylate polymer It closes；And temperature sensitive type water gel then uses the two kinds of derivatives and chitosan-mPEG and polyvinyl alcohol of polyethylene glycol (PVA) it is copolymerized.Can while pH and temperature be had by being prepared again by using semi-intercrossing network (Semi-IPN) technology The hydrogel medicine-carried system of double-response, the aquogel system have good biocompatibility and degradability, toxic side effect Very little.
PH sensitive hydrogel has good biocompatibility and degradability, and can pass through the ratio of adjusting three Example can be undergone phase transition under breast cancer tissue's microenvironment (when pH is 4.5-6.0), to discharge drug.Wherein, it adds Porous hemicellulose graft copolymerization acrylamide gel can effectively shorten drug release time.Two kinds of derivatives of polyethylene glycol For methacrylic acid 2- (2- methoxy ethoxy) ethyl ester (MEO2) and methacrylate (OEGMA) MA.By to four kinds of materials The regulation of material ratio can control the phase transition temperature of polyalcohol hydrogel to (39-41 at a temperature of breast cancer tissue's microenvironment DEG C), drug is discharged near breast cancer tissue.
The constituent of drug 4 is taxol, adriamycin, rheum emodin and He Saiting (Herceptin).Wherein, taxol It is a kind of natural secondary metabolite of bark separating-purifying from gymnosperm Chinese yew, the diterpene biology with anticancer activity Alkaloid compound can be effectively suppressed cell and carry out mitosis, is a kind of good antineoplastic vascular anti-proliferative agent.Adriamycin is A kind of common mammary cancer chemotherapy first-line drug, embeddable DNA and the synthesis for inhibiting nucleic acid, all to the tumour cell in various periods There is killing effect, while the toxic side effect of adriamycin is also fairly obvious, especially to the toxic side effect of heart, easily leads to rhythm of the heart mistake Often.Rheum emodin is a kind of orange-yellow long acicular crystal, has the effects that antibacterial, cough-relieving, antitumor, blood pressure lowering, in chemical structure It goes up and belongs to anthraquinone analog compound as the anticancer drugs such as adriamycin, daunorubicin, there is lipophilicity, meanwhile, rheum emodin can portion Divide the drug resistance for reversing adriamycins such as human breast cancer cell etc..He Saiting is a kind of monoclonal antibodies drug of peopleization, is One using oncogene as the therapeutic agent of the HER-2 positive breast metastasis of cancer patient of target, for human epidermal growth factor receptor 2 (HER-2) positive metastatic breast cancer has a better effect, while also having certain toxic side effect.Target proposed by the present invention The toxic side effect of drug normal tissue can be greatly reduced in the microcapsules that release drug is transported, pinpointed to collaboration.
The ingredient of magnetic material 3 is nanoscale ferroso-ferric oxide (Fe3O4), there is magnetism.It is micro- when coated ferriferrous oxide When capsule is passed through with body fluid flow to tumor tissues, under the action of externally-applied magnetic field, it is attached that microcapsules can be fixed on tumor tissues Closely.The ingredient of high-affinity modifier 2 is folic acid, is that a kind of complex of vitamin B and human body are utilizing sugar and amino Necessary material when sour.Folacin receptor in most of tumour cells all express by height, and folic acid and tumor cell surface folic acid Receptor has higher compatibility, and the targeting of drug, the efficiency that enhancing drug is absorbed by cell can be enhanced using folic acid.
As shown in Fig. 2, the hydrogel shell satellite liquid circulation when coating medicine, magnetic material and high-affinity modifier is defeated When being transported near tumor tissues, under the action of externally-applied magnetic field, the hydrogel shell microcapsules containing magnetisable material are fixed on Near tumor tissues.The temperature that slightly sour interior environment and tumor tissue cell are presented in view of tumor tissues is generally higher than normal Critical inversion, hydrogel occur with this condition for the pH- temperature Dual Sensitive type hydrogel of histiocytic temperature, microcapsules Volume undergo phase transition, the support surface area and wall structure of material are changed, to realize drug in tumor tissue cell Enrichment release, is conducive to tumor tissues absorption of drugs.Meanwhile after the magnetic material in microcapsules all discharges, Magnetic field just no longer has fixed function to microcapsules, thus microcapsules can be flowed with body fluid.When to flow to normal tissue thin for it When near born of the same parents, since the temperature near normal tissue cell is lower than near tumor tissue cell, and pH is higher than tumor tissue cell Near, by absorbing moisture volume expansion occurs for the hydrogel shunk, thus hydrogel volume restores original pattern again, thus Stop drug release, realizes the quick response of pharmaceutical carrier and the controllability of adaptive " on-off ", further realize master-passive target Collaboration transports, pinpoints and treat breast cancer near release drug to tumor tissue cell, effectively reduces drug to the poison of normal cell Side effect, while improving the transport efficiency and curative effect of drug.
Finally, it is stated that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to compared with Good embodiment describes the invention in detail, those skilled in the art should understand that, it can be to skill of the invention Art scheme is modified or replaced equivalently, and without departing from the objective and range of technical solution of the present invention, should all be covered at this In the scope of the claims of invention.

Claims (6)

1. the microcapsules that a kind of collaboration transported, pinpointed release drug therapy breast cancer, it is characterised in that: including hydrogel shell (1), drug (4), magnetic material (3) and high-affinity modifier (2)；The hydrogel shell (1) is in sphere or spheroid, institute State coating medicine (4), magnetic material (3) and high-affinity modifier (2) inside hydrogel shell (1).
2. a kind of collaboration according to claim 1 transports, pinpoints the microcapsules of release drug therapy breast cancer, feature exists In: the hydrogel shell (1) is combined by pH sensitive hydrogel with temperature sensitive type water gel, wherein pH responsive type Hydrogel is poly- by poly-aspartate (PASP) hydrogel, porous hemicellulose graft copolymerization acrylamide gel and acrylate Object is closed to be polymerized；And temperature sensitive type water gel then uses the two kinds of derivatives and chitosan-mPEG and poly- second of polyethylene glycol Enol (PVA) is copolymerized.
3. a kind of collaboration according to claim 2 transports, pinpoints the microcapsules of release drug therapy breast cancer, feature exists In: two kinds of derivatives of the polyethylene glycol are methacrylic acid 2- (2- methoxy ethoxy) ethyl ester (MEO2) and methyl-prop MA Olefin(e) acid ester (OEGMA).
4. a kind of collaboration according to claim 1 transports, pinpoints the microcapsules of release drug therapy breast cancer, feature exists In: the constituent of the drug (4) is taxol, adriamycin, rheum emodin and He Saiting (Herceptin).
5. a kind of collaboration according to claim 1 transports, pinpoints the microcapsules of release drug therapy breast cancer, feature exists In: the ingredient of the magnetic material (3) is nanoscale ferroso-ferric oxide (Fe3O4), there is magnetism.
6. a kind of collaboration according to claim 1 transports, pinpoints the microcapsules of release drug therapy breast cancer, feature exists In: the ingredient of the high-affinity modifier (2) is folic acid.
CN201910289436.XA 2019-04-11 2019-04-11 A kind of collaboration transports, pinpoints the microcapsules of release drug therapy breast cancer Pending CN109953976A (en)

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CN104945558A (en) * 2015-07-06 2015-09-30 安徽大学 Preparing method for multi-responsiveness polymer hollow microgel

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Application publication date: 20190702