WO2014048060A1 - Médicament anti-inflammatoire contre le cancer et le sida avec une radiothérapie et son procédé de préparation - Google Patents

Médicament anti-inflammatoire contre le cancer et le sida avec une radiothérapie et son procédé de préparation Download PDF

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Publication number
WO2014048060A1
WO2014048060A1 PCT/CN2013/001069 CN2013001069W WO2014048060A1 WO 2014048060 A1 WO2014048060 A1 WO 2014048060A1 CN 2013001069 W CN2013001069 W CN 2013001069W WO 2014048060 A1 WO2014048060 A1 WO 2014048060A1
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radioactive
mesoporous
nano
cancer
aids
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PCT/CN2013/001069
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English (en)
Chinese (zh)
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唐伟钊
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Tang Weizhao
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Priority claimed from CN201210388401.XA external-priority patent/CN103656692A/zh
Priority claimed from CN201210437128.5A external-priority patent/CN103768621A/zh
Application filed by Tang Weizhao filed Critical Tang Weizhao
Publication of WO2014048060A1 publication Critical patent/WO2014048060A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1241—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins
    • A61K51/1244—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins microparticles or nanoparticles, e.g. polymeric nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the invention relates to a nanometer manufacturing, a molecular biological anticancer drug and a radiotherapy anticancer technology, in particular to an anticancer anti-AIDS anti-inflammatory drug with radiotherapy and a preparation method thereof.
  • Anticancer drugs At present, cancer treatment at home and abroad is often treated by radiotherapy and chemotherapy, surgery or Chinese medicine. The radioactive substances used in hospital radiotherapy are only used by cancer patients. In order to deal with tumors, although there will be Dangerously, but the two evils are light and have to be used. The second treatment of cancer's traditional treatment method is greater than the cancer itself. This has been a global problem that has plagued modern medical treatment of cancer. One of the biggest obstacles to the application of traditional anti-cancer treatment is to kill tumor cells and often affect normal tissues. Cells that cause a variety of complications. Cancer Pathogenesis Cancer, also known as malignant tumor, is a disease caused by the abnormality of the cell growth and proliferation mechanism.
  • cancer cells can locally invade surrounding normal tissues and even transfer to other parts of the body via the circulatory system or lymphatic system. Because cancer cells can spread, metastasize or recur, many cancer patients often spend a lot of money after treatment. In general, the survival period is 3-5 years, and the extended life expectancy is very limited.
  • Traditional anti-cancer technology has obvious defects of secondary injury to cancer patients, shortcomings of short survival and high cost. Radiotherapy and chemotherapy can lead to greatly reduced immunity of cancer patients who have been destroyed by visceral function, and pose a greater hidden danger for cancer spread, metastasis and recurrence. This technology uses targeted or conventional anticancer drugs with radiotherapy, using targets.
  • Synergistic treatment and sustained-release treatment of other drugs increasing the intensity of treatment, on the one hand, greatly reducing the damage of skin and subcutaneous tissues and organs caused by traditional radiotherapy, greatly controlling the growth rate of cancer cells, on the other hand, relative Improve the patient's immunity and win valuable for treatment Time, the chance of eradicating the spread or transfer of mild cancer cells is greatly improved.
  • Anti-AIDS and anti-inflammatory drugs such as nucleoside reverse transcriptase inhibitors such as zidovudine, stavudine, didanosine, etc.
  • nucleoside reverse transcriptase inhibitors such as zidovudine, stavudine, didanosine, etc.
  • Non-nucleoside reverse transcriptase inhibitors such as nevirapine, protease inhibitors such as indinavir. They are used to treat AIDS by forming four internationally recognized "cocktail therapies": zidovudine + didanosine + nevirapine, didanosine + stavudine + nevirapine, zidovudine + dehydroxyl Inosine + indinavir, stavudine + didanosine + indinavir.
  • HIV genes can mutate and hide where drugs can't be killed, even when antiretroviral drugs (ARVs) are used to clear HIV in the body.
  • ARVs antiretroviral drugs
  • the level of blood is difficult to detect, some viruses remain active in tissues.
  • all anti-AIDS drugs at home and abroad can not cure AIDS patients fundamentally, but can effectively prolong the life of patients, which has been A global problem that plagues modern medicine for the treatment of AIDS.
  • This technology uses targeted or conventional anti-AIDS or anti-inflammatory infections with radiotherapy, and uses synergistic and sustained-release treatments for targeted drugs to increase the intensity of treatment.
  • the target with radiotherapy function Transmitting HIV or other anti-inflammatory or anti-inflammatory drugs to HIV-infected tissues and organs to kill HIV.
  • killing HIV through the humoral circulation and relatively improving the patient's immunity To gain valuable time for treatment, the chances of eliminating variability, spread, and metastasis of HIV have been greatly improved.
  • mesoporous radioactive nanospheres From the inside to the outside, mesoporous radioactive nanospheres, anti-radiation inert metal layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and anti-cancer anti-AIDS anti-inflammatory drug layer can also be eliminated; mesopores Put The surface of the radioactive nanospheres has a plurality of mesoporous radioactive nanospheres radiating mesopores and nano anti-radiation valves, and the nano anti-radiation valve is connected with the mesoporous radioactive nanospheres radiation mesopores; mesoporous radioactive nanospheres It can be made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials.
  • mesoporous radioactive nanospheres From the inside to the outside, mesoporous radioactive nanospheres, absorbing membrane layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and anti-cancer anti-AIDS anti-inflammatory drug layer can also be eliminated; mesoporous radioactivity
  • the surface of the nanosphere has a plurality of mesoporous radioactive nanospheres radiating mesopores and a nanometer radiation protection valve, and the nanometer radiation shielding gate is connected with the mesoporous radioactive nanospheres radiation mesopores; the mesoporous radioactive nanospheres can be They were made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials.
  • mesoporous radioactive nanospheres From the inside to the outside, there are mesoporous radioactive nanospheres, anti-radiation active metal film layer, metal and organic pollution protection film layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and can also eliminate the anti-antibody Cancer anti-AIDS anti-inflammatory drug layer; mesoporous radioactive nanospheres have numerous mesoporous radioactive nanospheres radiation mesopores and nano anti-radiation valves, nano anti-radiation valves and mesoporous radioactive nanospheres radiation mesoporous phase Connected and connected; mesoporous radioactive nanospheres can be made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials.
  • mesoporous radioactive nanospheres From the inside to the outside, there are mesoporous radioactive nanospheres, absorbing membrane layer, metal and organic pollution protection membrane layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and anti-cancer anti-cancer AIDS anti-inflammatory drug layer; when the absorbing membrane layer adopts non-toxic and non-bioreactive materials, the protective film layer against metal and organic pollution is removed; the mesoporous radioactive nanospheres have numerous mesoporous radioactive nanospheres radiating mesopores The mouth and nano radiation protection valve, the nano radiation protection wide door is connected with the mesoporous radioactive nano microsphere radiation mesoporous mouth; the mesoporous radioactive nano microsphere can be added with anti-cancer anti-AIDS anti-inflammatory by using radioactive material and internal mesoporous channel respectively The way the drug is made and the way the pure radioactive material is made.
  • mesoporous radioactive nanospheres From the inside to the outside, mesoporous radioactive nanospheres, radioactive metal film layer, anti-radiation layer, anti-cancer
  • the anti-AIDS anti-inflammatory drug layer and the nano-targeting carrier layer can also eliminate the anti-cancer anti-AIDS anti-inflammatory drug layer;
  • the mesoporous radioactive nanospheres have numerous mesoporous radioactive nano-microsphere radiation mesopores and nano anti-radiation valves.
  • the nano-radiation-proof valve is connected with the mesoporous radioactive nano-microsphere radiation mesopores; the mesoporous radioactive nano-spheres can be supplemented with radioactive materials and internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials. Way of making.
  • this technology uses targeted or conventional anti-cancer anti-inflammatory drugs with radiotherapy function, using targeted drugs Synergistic treatment and sustained-release treatment, increase the intensity of treatment, to achieve "significant reduction of skin and subcutaneous tissues and organs caused by traditional radiotherapy, greatly control the growth rate of cancer cells, HIV and inflammation, and relatively improve patients
  • the immunity for the treatment to win valuable time, the existing refractory cancer cells, HIV and inflammation or the spread or metastasis of mild cancer cells HIV and inflammation also eliminate the chance of a clean increase "good effect.
  • Radioactive nanospheres can be made of natural or artificial radioactive materials that can release particles or rays (such as alpha rays, 3 rays, xenon rays, etc.) from inside the nucleus.
  • the radiant energy is uranium (U). ⁇ (Th) and radium (Ra), or potassium - 40 (40K), ⁇ (Rb) and ⁇ (Cs), etc., or a mixture of radioactive materials and ceramic powder, and determine the required radioactive material according to actual conditions. kind of.
  • the specific gravity concentration of the drug after preparation is preferably consistent with the blood, for example, the specific gravity does not exceed the specific gravity of the blood 1. 05, so as to avoid precipitation.
  • the thickness is preferably thicker than 23 ⁇ m.
  • the radiation-proof inert metal or absorbing layer may be made of various radiation-proof inert metals such as gold or silver or silica gel.
  • the solution of the drug can be filtered by a set aperture.
  • individual drugs may not be completely excreted by metabolism within the specified time, and may be filtered by hemodialysis. If necessary, magnetic substances may be added to both the filter membrane and the mesoporous radioactive nanospheres. Magnetic absorption and other methods are better filtered.
  • the anti-cancer anti-AIDS anti-inflammatory drug layer may be a targeted or conventional drug layer.
  • mesoporous radioactive nanospheres From the inside to the outside, mesoporous radioactive nanospheres, anti-radiation inert metal layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and anti-cancer anti-AIDS anti-inflammatory drug layer can also be eliminated; mesopores
  • the surface of the radioactive nanospheres has a plurality of mesoporous radioactive nanospheres radiating mesopores and nano anti-radiation valves, and the nano anti-radiation valve is connected with the mesoporous radioactive nanospheres radiation mesopores; the mesoporous radioactive nanospheres can be They were made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials.
  • mesoporous radioactive nanospheres From the inside to the outside, mesoporous radioactive nanospheres, absorbing membrane layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and anti-cancer anti-AIDS anti-inflammatory drug layer can also be eliminated; mesoporous radioactivity
  • the surface of the nanosphere has a plurality of mesoporous radioactive nanospheres radiating mesopores and a nanometer radiation protection valve, and the nanometer radiation protection valve is connected with the mesoporous radioactive nanospheres radiation mesopores; the mesoporous radioactive nanospheres can be separately It is made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials. 3.
  • mesoporous radioactive nanospheres From the inside to the outside, there are mesoporous radioactive nanospheres, anti-radiation active metal film layer, metal and organic pollution protection film layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and can also eliminate the anti-antibody Cancer anti-AIDS anti-inflammatory drug layer; mesoporous radioactive nanospheres have numerous mesoporous radioactive nanospheres radiation mesopores and nano anti-radiation valves, nano anti-radiation valves and mesoporous radioactive nanospheres radiation mesoporous phase Connected and connected; mesoporous radioactive nanospheres can be made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials.
  • mesoporous radioactive nanospheres From the inside to the outside, there are mesoporous radioactive nanospheres, absorbing membrane layer, metal and organic pollution protection membrane layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and anti-cancer anti-cancer AIDS anti-inflammatory drug layer; when the absorbing membrane layer adopts non-toxic and non-bioreactive materials, the protective film layer against metal and organic pollution is removed; the mesoporous radioactive nanospheres have numerous mesoporous radioactive nanospheres radiating mesopores The mouth and nano anti-radiation valve, the nano anti-radiation valve is connected with the mesoporous radioactive nano-microsphere radiation mesopores; the mesoporous radioactive nano-spheres can be added with anti-cancer anti-inflammatory drugs by radioactive materials and internal mesoporous channels, respectively. The way and the way of purely radioactive materials are produced.
  • mesoporous radioactive nanospheres From the inside to the outside, mesoporous radioactive nanospheres, radioactive metal film layer, radiation protection layer, anti-cancer anti-inflammatory anti-inflammatory drug layer, nano-targeting carrier layer, and anti-cancer anti-AIDS anti-inflammatory drug layer can also be eliminated.
  • the mesoporous radioactive nanospheres have a plurality of mesoporous radioactive nanospheres radiating mesopores and nanometer radiation protection valves, and the nanometer radiation protection valve is connected with the mesoporous radioactive nanospheres radiation mesopores; mesoporous radioactive nanometers; Microspheres can be made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs and pure radioactive materials.
  • the mesoporous size of mesoporous radioactive nanospheres is preferably controlled in the range of 2 to 50 nm.
  • mesoporous radioactive nanospheres and nano-radiation-proof wide doors can be assembled by assembly or other chemical methods, but self-assembly is preferred to achieve mass production.
  • Mesoporous radioactive nanospheres can be prepared by adding radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs or pure radioactive materials.
  • this technology uses targeted or conventional anti-cancer anti-inflammatory drugs with radiotherapy, targeting drugs Synergistic treatment and sustained-release treatment, increase the intensity of treatment, to achieve "significant reduction of skin and subcutaneous tissues and organs caused by traditional radiotherapy, greatly control the growth rate of cancer cells, HIV and inflammation, and relatively improve patients
  • the immunity for the treatment to win valuable time, the existing refractory cancer cells, HIV and inflammation or the spread or metastasis of mild cancer cells HIV and inflammation also eliminate the chance of a clean increase "good effect.
  • Figure 1 is a cross-sectional view and a schematic view of the present invention.
  • mesoporous radioactive nanospheres 21A, radiation-proof inert metal layer, 3A, anti-cancer anti-AIDS anti-inflammatory drug layer, 4, mesoporous radioactive nanospheres radiation mesopores, 5, nano-anti Radiation valve, 5A, quasi-rotaxane or rim "spool", 6, nano-targeting carrier layer.
  • Figure 2 is a cross-sectional view of the present invention.
  • Figure 3 is a cross-sectional view of the present invention.
  • Figure 4 is a cross-sectional view of the present invention.
  • Figure 5 is a cross-sectional view of the present invention.
  • Fig. 6 is a super-molecular structure diagram of a pseudo-rotaxane in which a radiation-proof metal cluster of one of the structures of the nano-radiation-proof valve (5) is a core.
  • FIG. 1 and FIG. 2 are respectively a structural enlarged cross-sectional view of an anti-cancer anti-inflammatory anti-inflammatory drug with radiotherapy and a preparation method thereof.
  • Step 1 Preparation of a nano-radiation-proof valve with a radiation-proof metal ion on the surface (5) Functional mesoporous radioactivity Nanospheres (1):
  • Radioactive materials such as natural or artificial uranium (U), thorium (Th) and radium (Ra), or potassium-40 (40K) that emit particles or rays (such as d-rays, beta rays, xenon rays, etc.) from inside the nucleus.
  • Radioactive materials such as lanthanum (Rb) and lanthanum (Cs) and silica hybrid materials or individual radioactive materials are used as substrates, by chemical or biosynthetic or mechanical methods such as coprecipitation, sol-gel, dispersion polymerization or Controlled free radical polymerization to synthesize uniform size, large pore volume (for example, 0. 6-5cm3/g), high specific surface area (for example, 700--1500 m2/g), high-density modified radioactive mesoporous radioactive nanometer Microspheres (1), for example: can be prepared by the following methods, etc.
  • Method 1 After mixing the calcium carbonate and radium radioactive materials, the mechanically ground powder is added to the nanometer size, and the gel is desolvated and washed with dilute acid.
  • the preparation method comprises: preparing radioactive particles by coprecipitation; then dispersing the washed radioactive particles directly into an aqueous solution of a SiO2-containing water-soluble inorganic salt for coating or mixing with an inorganic silicon source; Trimethylammonium bromide is used as a templating agent, and tetraethyl orthosilicate is a silicon source for mesoporous silica coating or mixing.
  • Method 3 using a sodium hypophosphite liquid phase reduction method to prepare a nano-ray sol, and then using tetraethyl orthosilicate as a silicon source, cetyltrimethylammonium bromide as a template, using a sol-gel method,
  • the silica spherical shell was grown in situ on the surface of the radium particles in the prepared nano-laser sol, and then the organic template was removed by solvent extraction, and the mesoporous silica-coated radium nanoparticles were prepared by supercritical drying.
  • Method 4 if the patent number is 03153265, the name is "a preparation method of a micrometer spherical mesoporous silica", and the patentee is authorized by the "Institute of Physical and Chemical Technology of the Chinese Academy of Sciences", and can be prepared by the following method steps,
  • the method comprises the following steps: (1) preparing an acid solution, the concentration of the acid is Q. 0 1 ⁇ 10 mol/L; 2) adding a surfactant to the solution of the step (1), so that the cetyltrimethyl group in the mixed solution
  • the concentration of ammonium halide is 0. 0 0 1 ⁇ 5 mol / liter, the concentration of polyvinyl alcohol is 0.
  • the mesoporous surface inside the mesoporous radioactive nanospheres (1) is successfully grafted or physically adsorbed against the anti-cancer anti-inflammatory drugs, and the anti-cancer, anti-AIDS and anti-inflammatory drugs are prepared.
  • the drug's pore radioactive nanospheres (1); mesoporous radioactive nanospheres (1) can be made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs or pure radioactive materials.
  • a method such as a volatilization method for example, a metal rim having a function of a nano-radiation-proof valve (5) having a radiation-proof metal ion on the surface or a metal rim having a function of a nano-radioactive material (5) having a radiotherapy function, for example, (1):
  • a volatilization method for example, a metal rim having a function of a nano-radiation-proof valve (5) having a radiation-proof metal ion on the surface or a metal rim having a function of a nano-radioactive material (5) having a radiotherapy function, for example, (1):
  • the artificial radioisotope cobalt 60 which can replace X-rays for the treatment of cancer and AIDS, as an example, the rotaxane produced by cucurbituril and spermine hydrochloride is self-assembled with hydrated alkyl cobalt ruthenium.
  • New methods of self-assembly (if they or the unit has applied for a patent, they need to obtain the license of the patentee), specifically: use Radiation metal cluster core conduct self-assembly as a ligand, namely: synthetic anionic organic ligand radiation regulatory guidance metal clusters, then macrocycle Coordination with a radiation-proof metal cluster to produce a radiation-proof metal cluster assembly having a specific coordination direction, and then using other ligands as a linker, thereby obtaining a quasi-rim, a hydrocarbon-locking, etc.
  • Radiation metal cluster core conduct self-assembly as a ligand, namely: synthetic anionic organic ligand radiation regulatory guidance metal clusters, then macrocycle Coordination with a radiation-proof metal cluster to produce a radiation-proof metal cluster assembly having a specific coordination direction, and then using other ligands as a linker, thereby obtaining a quasi-rim, a hydrocarbon-locking, etc.
  • a radiation-proof metal cluster as a core Molecular structure; for example, (3):
  • metal ions as a template or the introduction of metal ions and their complexes in supermolecular systems such as rotaxanes and hydrocarbons has synthesized a variety of novel supermolecules such as metal rotaxanes and hydrocarbons.
  • the supermolecular quasi-rim or rim of silver metal is constructed on the surface of mesoporous radioactive nanospheres (1) by means of self-assembly, etc., and functionalized nano-silica or nano-silver is used as a bobbin molecule, and super-molecules such as silver metal can be online.
  • a supramolecular nano-radiation-proof valve (5) that slides on the shaft, controls the release and the new function of the switch, thereby obtaining a mesoporous radioactive nanosphere (1) with a functional anti-radiation metal ion on the surface of the nano-radiation-proof valve (5) Controlled release of supramolecular nanovalves such as silver metal by pH and competition combined with dual channels, etc., to meet various release and switching requirements of the set conditions.
  • the mesoporous radioactive nanospheres (1) are nano-containers, and the nano-targeting carrier layer (6) is controlled release of a supramolecular nano-valve such as silver metal induced by an amino acid decarboxylase, which has biological targeting and switching functions.
  • the switch of the nano-radiation-proof valve (5) is automatically opened, and the anti-cancer anti-inflammatory and anti-inflammatory drugs inside the mesoporous radioactive nanospheres (1) pass through the mesoporous radioactivity.
  • the nano-microspheres radiate mesopores (4) to release outward, and "chemotherapy” kills cancer cells, HIV and inflammation; the switch of nano-radiation-proof valve (5) is automatically opened while mesoporous radioactivity
  • the radiation inside the nanosphere (1) is radiated externally through the mesoporous radioactive nanosphere irradiation mesopores (4), and the cancer cells, HIV and inflammation of the target cancer tissue are "radiated”;
  • the anti-cancer anti-inflammatory anti-inflammatory drug layer (3A) routinely kills cancer cells, HIV and inflammatory chemotherapy or Chinese medicine treatment of target cancer cells; the above process is performed separately or simultaneously with radiotherapy and chemotherapy.
  • Step 2 Coating or plating the radiation-proof inert metal layer (21A) or the absorber film layer (21B) onto the mesoporous radioactive nanospheres (1):
  • Step 3 Coating, covering or adsorbing the anti-cancer anti-inflammatory drug layer (3A) in the radiation-proof inert metal layer (21A) or sucking by physical adsorption, chemical infiltration, copolymerization, magnetization, surface modification, etc. On the wave film layer (21B).
  • Step 4 Prepare a nano-targeted carrier layer by compounding a targeting agent such as lipase by chemical modification and polymerization (6).
  • Step 5 The nano-targeting carrier layer (6) is coated and covered on the anti-cancer anti-inflammatory anti-inflammatory drug layer (3A) by modification, magnetization, copolymerization and the like.
  • Radioactive nanospheres (1), anti-radiation inert metal layer (21A) or absorbing membrane layer (21B), anti-cancer anti-AIDS anti-inflammatory drug layer (3A), mesoporous radioactive nanospheres radiation mesoporous ( 4), a nano-radiation-proof broad-door (5), a nano-targeted carrier layer (6), a radiotherapy-resistant anti-cancer anti-inflammatory drug and a preparation method thereof, as an injection for blood injection or intramuscular injection or incision injection or After oral administration as an oral drug, the drug is absorbed into the blood circulation system and the lymphatic system of the body with blood or gastrointestinal absorption.
  • the anti-cancer anti-AIDS anti-inflammatory drug is caused by the organism.
  • the guiding effect is concentrated on the target site cancer tissues and cancer cells, HIV and inflammatory cells; anti-cancer anti-AIDS anti-inflammatory drugs are killed with the blood circulation to the whole body of cancer tissue cells, in the external electricity, light, magnetic,
  • the valve is "open" when the molecular ring of the quasi-rotaxane or rim “spool” (5A) in the nano-radiation-proof valve (5) is driven upward by electrical or magnetic force.
  • the radiation in the mesoporous radioactive nanospheres (1) is killed by mesoporous radioactive nanospheres through the mesopores (4) to kill cancer cells, HIV and inflammation of the target cancer tissue;
  • Nano micro The anti-cancer anti-inflammatory and anti-inflammatory drugs adsorbed by the mesoporous channel of the ball (1) are released through the mesoporous radioactive nanospheres through the mesopores (4), and the cancer cells, HIV and inflammation of the target cancer tissues are carried out.
  • Radioactive nanospheres (1), anti-radiation inert metal layer (21A) or absorbing membrane layer (21B), anti-cancer anti-AIDS anti-inflammatory drug layer (3A), mesoporous radioactive nanospheres radiation mesoporous ( 4), a nano-anti-radiation valve (5), a nano-targeting carrier layer (6), a radiotherapy-resistant anti-cancer anti-inflammatory drug and a preparation method thereof, as an injection for blood injection or intramuscular injection or incision injection or as an injection After oral administration, the drug is absorbed into the blood circulation system and lymphatic system of the body with blood or gastrointestinal absorption.
  • the anti-cancer and anti-AIDS resistance due to biological guidance Inflammatory drugs are concentrated in cancerous tissues and cancer cells, HIV and inflammatory cells at target sites, killing cancer cells, HIV and inflammation; and anti-cancer anti-inflammatory drugs are circulating to the whole body of cancer tissue cells with blood circulation. Killing, this is the process of releasing anti-cancer anti-inflammatory drugs.
  • Fig. 3 or Fig. 4 are respectively a macroscopic enlarged view of a structural section of an anticancer, anti-AIDS and anti-inflammatory drug with radiotherapy and a preparation method thereof:
  • Step 1 Preparation of a nano-radiation-proof valve with a radiation-proof metal ion on the surface (5) Mesoporous radioactivity of a functional group Nanospheres (1):
  • a radioactive material and a silica hybrid material or a separate radioactive material as a substrate, using chemical or biosynthetic or mechanical methods such as coprecipitation, sol-gel method, dispersion polymerization or controllable freedom
  • Base polymerization method for synthesizing uniform size, large pore volume (for example, 0.6--5 cm3/g), high specific surface area (for example, 700-1500 m2/g), high density modified radioactive mesoporous radioactive nanospheres ( 1) for example: It can be prepared by the following methods, etc. The following methods are the same as those in Fig. 1, and are omitted.
  • the mesoporous surface inside the mesoporous radioactive nanospheres (1) is successfully grafted or physically adsorbed against the anti-cancer anti-inflammatory drugs, and the anti-cancer, anti-AIDS and anti-inflammatory drugs are prepared.
  • the drug's pore radioactive nanospheres (1); mesoporous radioactive nanospheres (1) can be prepared by adding radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs or by using pure radioactive materials alone.
  • the following method is used to obtain a metal rim of a nano-radiation-proof wide gate (5) functional group having a radiation-proof metal ion on the surface, specifically a rim-like rim produced by cucurbituril and spermine hydrochloride, and a hydrated ruthenium-based cobalt
  • a new type of metal rotaxane is formed in the aqueous solution, which is one of the methods to be realized.
  • the supermolecular quasi-rim or rim of silver metal is constructed on the surface of mesoporous radioactive nanospheres (1) by means of self-assembly, etc., and functionalized nano-silica or nano-silver is used as a bobbin molecule, and super-molecules such as silver metal can be online.
  • a supramolecular nano-radiation-proof valve (5) that slides on the shaft, controls the release and the new function of the switch, thereby obtaining a mesoporous radioactive nanosphere (1) with a functional base of a nano-radiation-proof valve (5) with a radiation-proof metal ion on the surface (1)
  • the mesoporous radioactive nanospheres (1) are nano-containers
  • the nano-targeting carrier layer (6) such as an amino acid decarboxylase, is a supramolecular nanovalve such as silver metal.
  • the transport system has biological targeting and switching capabilities and is capable of controlled release in multiple steps as needed.
  • the switch of the nano-radiation-proof valve (5) is automatically opened, and the anti-cancer anti-inflammatory and anti-inflammatory drugs inside the mesoporous radioactive nanospheres (1) pass through the mesoporous radioactivity.
  • the nano-microspheres radiate mesopores (4) to release outward, and "chemotherapy” kills cancer cells, HIV and inflammation; the switch of nano-radiation-proof valve (5) is automatically opened while mesoporous radioactivity
  • the radiation inside the nanosphere (1) is radiated externally through the mesoporous radioactive nanosphere irradiation mesopores (4), and the cancer cells, HIV and inflammation of the target cancer tissue are "radiated”;
  • the anti-cancer anti-inflammatory anti-inflammatory drug layer (3A) routinely kills cancer cells, HIV and inflammatory chemotherapy or Chinese medicine treatment of target cancer cells; the above process is performed separately or simultaneously with radiotherapy and chemotherapy.
  • Step 2 Coating or plating the radiation-proof active metal film layer (22A) or the absorber film layer (21B) onto the mesoporous radioactive nanospheres (1): radiation-proof active metal film layer (22A) or absorbing wave
  • the film layer (21B) is subjected to physical adsorption method, arc discharge method, plasma polymerization method, laser chemical vapor deposition method, chemical replacement method, emulsion polymerization method, surface deposition method (electroless plating method, heterogeneous precipitation method), and the like.
  • the metal or organic contamination protective film layer (31) is coated or plated onto the mesoporous radioactive nanospheres (1).
  • Step 3 The metal or organic contamination protective film layer (31) is coated or plated onto the radiation-proof active metal film layer (22A) or the moisture absorbing film layer (21B).
  • Step 4 Coating, covering or adsorbing the anti-cancer anti-inflammatory anti-inflammatory drug layer (3A) in a metal or organic-protective protective film layer by physical adsorption, chemical infiltration, copolymerization, magnetization, surface modification, etc. (31 ).
  • Step 5 Prepare a nano-targeted carrier layer by compounding a targeting agent such as lipase by chemical modification and polymerization (6).
  • Step 6 The nano-targeting carrier layer (6) is coated and covered on the anti-cancer anti-AIDS anti-inflammatory drug layer (3A) by means of modification, magnetization, copolymerization and the like.
  • 3A anti-cancer anti-AIDS anti-inflammatory drug layer
  • Radioactive nanospheres (1), radiation-proof active metal film layer (22A) or absorbing film layer (21B), metal or organic-protective protective film layer (31), anti-cancer anti-AIDS anti-inflammatory drug layer (3A a mesoporous radioactive nano-microsphere radiation mesoporous (4), nano-radiation-proof valve (5), quasi-rim or rotaxane "broad core” (5A), nano-targeting carrier layer (6)
  • anti-cancer anti-AIDS and anti-inflammatory drugs are concentrated to target sites of cancer tissues and cancer cells, HIV and inflammatory cells due to biological targeting; anti-cancer and anti-AIDS resistance Inflammatory drugs are killed by the blood cells circulating to the whole body of cancer tissue cells.
  • the molecular ring of the "spool” (5A) When the molecular ring of the "spool” (5A) is driven upward by electric or magnetic force, the valve is in the "on” state, and the radiation in the mesoporous radioactive nanosphere (1) passes through the mesoporous radioactive nanometer
  • the spherical radiation mesopores (4) kill cancer cells, HIV and inflammation of the target cancer tissue; and the anticancer anti-AIDS anti-inflammatory drugs adsorbed by mesoporous radioactive nanospheres (1) mesoporous channels Through the mesoporous radioactive nanospheres, the radiation mesopores (4) are released to the outside, and the cancer cells, HIV and inflammation of the target cancer tissue are killed; when the nano-radiation valve (5) is quasi-rotaxane or The rim "spool" (5A) The downward movement of the molecular ring blocks the mesopor
  • the mesoporous radioactive nanospheres are irradiated.
  • the mesopores (4) are closed, and the radiation in the mesoporous radioactive nanospheres (1) and the anticancer anti-inflammatory anti-inflammatory drugs in the mesopores stop the radiation or anti-cancer anti-inflammatory drugs. This is radiotherapy. And sustained release anti-cancer anti-AIDS Process control anti-inflammatory drugs.
  • the anti-cancer, anti-inflammatory and anti-inflammatory effects due to biological guidance Drugs are concentrated in target sites, cancerous tissues and cancer cells, HIV and inflammatory cells, killing cancer cells, HIV and inflammation; while anti-cancer, anti-AIDS and anti-inflammatory drugs are carried out with blood circulation to cancer cells of the body. Killing, this is the process of releasing anti-cancer, anti-AIDS and anti-inflammatory drugs.
  • Figure 5 is a macroscopic enlarged view of a structural cross-sectional view of an anti-cancer anti-inflammatory drug with radiotherapy and a preparation method thereof:
  • Step 1 Prepare a nano-radiation-proof valve with a radiation-proof metal ion on the surface (5) Mesoporous radioactivity of the functional group Nanospheres (1):
  • a large pore volume for example, 0.6- 5 cm3/g
  • a high specific surface area for example, 700-1500 m2/g
  • a high-density modified radioactive mesoporous radioactive nanosphere (1) for example -
  • the following methods are used to prepare, etc., and the following methods are the same as those in Fig. 1, and are omitted.
  • the mesoporous radioactive nanospheres (1) After the mesoporous radioactive nanospheres (1) are prepared, the mesoporous surface inside the mesoporous radioactive nanospheres (1) is successfully grafted or physically adsorbed against the anti-cancer anti-inflammatory drugs, and the anti-cancer, anti-AIDS and anti-inflammatory drugs are prepared.
  • the drug's pore radioactive nanospheres (1); mesoporous radioactive nanospheres (1) can be made by means of radioactive materials plus internal mesoporous channels to add anti-cancer anti-inflammatory drugs or pure radioactive materials. Due to the strong or very strong coordination bond between metal ions and metal and ligand, it becomes the driving force for self-assembly of supramolecules.
  • the structural and functional components or building blocks of molecules such as molecules are assembled into new supramolecular compounds in a designed manner, and the surface-radioactive nano-radiation-proof valves are obtained by interaction or bonding between metal and metal molecules (5)
  • the functional group of mesoporous radioactive nanospheres (1) can be directly bound or obtained by chemical modification.
  • the following method is used to obtain a metal rotaxane having a functional surface of a radioactive nano-radiation-proof valve (5), specifically a rim-like rim produced by cucurbituril and spermine hydrochloride, and self-assembled with hydrated ruthenium-based cobalt ruthenium. After the reaction, a new type of metal rim is formed in the aqueous solution, which is one of the methods implemented.
  • a supermolecular quasi-rim or rim of silver metal is constructed on the surface of mesoporous radioactive nanospheres (1) by self-assembly, etc., and functionalized nano-silica or nano-silver is used as a bobbin molecule, and supramolecules such as silver metal can be online.
  • a supramolecular nano-radiation-proof valve (5) that slides on the shaft, controls the release and the new function of the switch, thereby obtaining a mesoporous radioactive nanosphere (1) with a functional surface-based radioactive nano-radiation-proof valve (5), through pH Combined with competition, the dual-channel and other super-molecular nano-controlled release such as silver metal can meet the various release and switching requirements of the set conditions.
  • the mesoporous radioactive nanospheres (1) are nano-containers, and the nano-targeting carrier layer (6) is controlled release of a supramolecular nano-valve such as silver metal induced by an amino acid decarboxylase, which has biological targeting and switching functions. And can control the release in multiple steps as needed. Under the action and control of the external electricity, light, magnetism, sound, etc., the switch of the nano-radiation-proof valve (5) is automatically opened, and the anti-cancer, anti-inflammatory and anti-inflammatory drugs inside the mesoporous radioactive nanospheres (1) are introduced.
  • a supramolecular nano-valve such as silver metal induced by an amino acid decarboxylase
  • the radioactive nano-microspheres radiate mesopores (4) to release outward, and "chemotherapy” kills cancer cells, HIV and inflammation; the switch of the nano-radiation valve (5) is automatically opened,
  • the radiation inside the porous radioactive nanosphere (1) radiates externally through the mesoporous radioactive nano-microsphere radiation mesopores (4) and the radiation of the nano-radiation-proof valve (5) itself, and the cancer of the target cancer tissue Cells, HIV and inflammation undergo “radiotherapy”killing; on the other hand, anti-cancer anti-inflammatory anti-inflammatory drug layer (3A) targets cancer cells, HIV and inflammatory chemotherapy or Traditional Chinese medicine treatment is routinely and rapidly killed; the above process is performed by radiotherapy and chemotherapy alone or simultaneously.
  • Step 2 Coating or plating the radioactive metal film layer (21C) onto the mesoporous radioactive nanospheres (1):
  • the radiation prevention layer (32) is applied by physical adsorption method, arc discharge method, plasma polymerization method, laser chemical vapor deposition method, chemical replacement method, emulsion polymerization method, surface deposition method (electroless plating method, heterogeneous precipitation method) or the like. ) coated or plated onto mesoporous radioactive nanospheres (1).
  • Step 3 Cover or plate the radiation protection layer (32) onto the radioactive metal film layer (21C).
  • Step 4 The anti-cancer anti-AIDS anti-inflammatory drug layer (3A) is coated, covered or adsorbed on the radiation protection layer (32) by physical adsorption, chemical infiltration, copolymerization, magnetization, surface modification, and the like.
  • Step 5 A nano-target carrier layer is prepared by compounding a targeting carrier such as lipase by chemical modification and polymerization (6).
  • Step 6 The nano-targeting carrier layer (6) is coated and covered on the anti-cancer anti-AIDS anti-inflammatory drug layer (3A) by modification, magnetization, copolymerization and the like.
  • the molecular ring of the quasi-rotaxane or rim "spool" (5A) in the nano-radiation-proof valve (5) is electrically Or when the magnetic force drives the upward movement, the valve is in an "on” state, and the radiation in the mesoporous radioactive nanosphere (1) passes through the mesoporous radioactive nanospheres to irradiate the mesopores (4) to the target cancer tissue.
  • HIV anti-cancer inflammatory drugs or anti-cancer radiation stopping the flow outwardly inflammatory drugs against AIDS, which is a sustained release anti-cancer radiotherapy and process control HIV anti-inflammatory drugs.
  • bio-directed anti-cancer anti-inflammatory drugs are concentrated in target sites of cancer tissues and cancer cells, HIV and inflammatory cells, killing cancer cells, HIV and inflammation; and anti-cancer, anti-AIDS and anti-inflammatory
  • the drug is killed by the blood cells circulating to the cancer cells of the whole body. This is the process of
  • anticancer drug experimental example 1 ( Figure 1 for the experimental example).
  • an anticancer drug such as a cisplatin drug molecule is successfully grafted on the surface of the mesoporous radioactive nanosphere (1), and the anticancer drug layer (3A) such as cisplatin is coated by copolymerization and self-assembly.
  • the drug molecule is coated with a nano-targeting carrier layer (6) on the surface of the anticancer drug layer (3A), such as a cisplatin drug molecule, and the results show that the drug loading efficiency is 50 due to coordination and superior adsorption performance of the material. %, slow release of the drug lasts for 20 days.
  • the release system has pH-sensitive release characteristics, and at the same drug concentration, the drug delivery system is more effective in inhibiting human cervical cancer cells than conventional drugs, and at the same time, the anticancer drug layer (3A) is treated with chemotherapy.
  • Mesoporous radioactive nanospheres (1) capable of emitting alpha-rays as a radioactive substance through a mesoporous radioactive nanosphere-radiating mesoporous port (4) for radiotherapy of target cancer cells, after 1 hour of treatment, The killing rate of cancer cells at the cervical targeting site reaches 100%.
  • mesoporous radioactive nanospheres (1) mesoporous radioactive nanospheres (1), radiation-proof active metal film layer (21B), metal-proof organic a pollution prevention protective layer (31), an anticancer drug layer (3A), a mesoporous radioactive nanosphere radiation mesopores (4), a nanometer radiation protection valve (5), and a nanotarget carrier layer (6)
  • a nano-anticancer drug with radiotherapy function is
  • Radioactive nanospheres (1) synthesized by chemical methods, such as radium, which is capable of emitting alpha ray as a radioactive substance, successfully grafted an anticancer targeting or conventional drug layer such as doxorubicin internally using a mesoporous surface.
  • the drug molecule is coated with an anticancer drug layer (3 ⁇ ), such as a cisplatin drug molecule, by copolymerization, self-assembly or magnetization, and then coated with an enzyme on the surface of the anticancer drug layer (3 ⁇ ) such as cisplatin drug molecule.
  • the drug delivery system nano-targeted carrier layer (6) which exhibits extremely high doxorubicin loading (800 mg/g) and loading efficiency (60%).
  • the drug-loading system can achieve targeted therapy of liver cancer.
  • the results showed that the synthesized ligand-functionalized drug delivery system was more effectively recognized by liver cancer cells than the unfunctionalized vector, and showed more effective than conventional drugs and unfunctionalized mesoporous nano drug delivery systems.
  • the anticancer drug layer (3A) performs chemotherapy, and the mesoporous radioactive nanospheres (1) that set the radiation ⁇ -rays pass through the mesoporous radioactive nanospheres to irradiate the mesopores (4) to the target cancer cells.
  • the kill rate of cancer cells at the liver-targeted site reached 100%.
  • Nano-targeting carrier layer A nano anti-AIDS or anti-inflammatory drug with radiotherapy function.
  • One DC power supply with 24V voltage with electrodes.
  • the results show that due to coordination
  • the release system has a pH-sensitive release property, and at the same drug concentration, the drug delivery system is more effective in inhibiting cervical HIV than the conventional drug, and at the same time, the anti-AIDS anti-inflammatory drug layer (3A) is treated with chemotherapy.
  • a radioactive nano-sphere (1) capable of emitting alpha-rays as a radioactive substance through a mesoporous radioactive nanosphere-radiating mesoporous (4) combination of target radiotherapy for HIV, from the results of the test
  • 93% of AIDS patients who were simultaneously injected and taken with anti-AIDS targeted drugs containing the novel integrase inhibitors did not detect the virus.
  • anti-AIDS anti-inflammatory drugs experimental example 2 ( Figure 3 for the experimental example).
  • mesoporous radioactive nanospheres (1) mesoporous radioactive nanospheres (1), radiation-proof active metal film layer (22 ⁇ ), metal and organic pollution protection film layer (31), anti-AIDS and anti-inflammatory drug layer (3 ⁇ ), mesoporous radioactive nano-micro A nano-anti-AIDS or anti-inflammatory drug with radiotherapy function consisting of a spherical radiation mesoporous (4), a nano-radiation-proof valve (5), and a nano-targeted carrier layer (6).
  • the surface of the inhibitor molecule is coated with an enzyme-trigger delivery system nano-targeted carrier layer (6) which exhibits a very high new integrase inhibitor loading (800 mg/g) and loading efficiency (60%).
  • the results showed that the synthesized ligand-functionalized drug delivery system was more effectively recognized by hepatic HIV than the unfunctionalized vector, and showed more than conventional drugs and unfunctionalized mesoporous nano drug delivery systems. Effective killing effect on HIV.
  • the anti-AIDS anti-inflammatory drug layer (3A) is treated with the mesoporous radioactive nanospheres (1) that set the radiation beta-rays through the mesoporous radioactive nanospheres to irradiate the mesopores (4) to the target.
  • 90% of AIDS patients who were injected and taken with anti-AIDS targeted drugs containing novel integrase inhibitors were not detected at 48 weeks after treatment.

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Abstract

L'invention concerne un médicament anti-inflammatoire contre le cancer et le SIDA avec une radiothérapie, et son procédé de préparation. Le médicament, de l'intérieur vers l'extérieur, dans cet ordre, est composé de nanosphères mésoporeuses radioactives (1), d'une couche de métal inerte résistant au rayonnement (21A), d'une couche facultative de médicament anti-inflammatoire contre le cancer et le SIDA (3A) et d'une couche de support de nano-ciblage (6). De nombreuses ouvertures mésoporeuses de rayonnement de nanosphère mésoporeuse radioactive (4) et de nombreuses valves résistantes au nanorayonnement (5) se trouvent sur la surface d'une nanosphère mésoporeuse radioactive (1), lesquelles sont en relation et en communication les unes avec les autres.
PCT/CN2013/001069 2012-09-25 2013-09-13 Médicament anti-inflammatoire contre le cancer et le sida avec une radiothérapie et son procédé de préparation WO2014048060A1 (fr)

Applications Claiming Priority (4)

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CN201210388401.X 2012-09-25
CN201210388401.XA CN103656692A (zh) 2012-09-25 2012-09-25 一种带放疗功能的纳米靶向或常规抗癌药物及其制备方法
CN201210437128.5A CN103768621A (zh) 2012-10-22 2012-10-22 一种带放疗功能的纳米靶向或常规抗艾滋病或抗炎性感染药物及其制备方法
CN201210437128.5 2012-10-22

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1579935A (zh) * 2003-08-12 2005-02-16 中国科学院理化技术研究所 微米球形介孔二氧化硅的制备方法
CN101234217A (zh) * 2008-03-07 2008-08-06 北京蓝景创新科技有限公司 一种功能性靶向治疗可降解的生物支架
US20110268791A1 (en) * 2009-01-05 2011-11-03 Juewen Liu Porous nanoparticle supported lipid bilayer nanostructures
CN102249248A (zh) * 2011-06-11 2011-11-23 中国海洋大学 单分散球形介孔二氧化硅纳米材料及制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1579935A (zh) * 2003-08-12 2005-02-16 中国科学院理化技术研究所 微米球形介孔二氧化硅的制备方法
CN101234217A (zh) * 2008-03-07 2008-08-06 北京蓝景创新科技有限公司 一种功能性靶向治疗可降解的生物支架
US20110268791A1 (en) * 2009-01-05 2011-11-03 Juewen Liu Porous nanoparticle supported lipid bilayer nanostructures
CN102249248A (zh) * 2011-06-11 2011-11-23 中国海洋大学 单分散球形介孔二氧化硅纳米材料及制备方法

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