WO2022134408A1 - Injection de microsphères de verre radioactves, méthode de préparation et utilisation - Google Patents

Injection de microsphères de verre radioactves, méthode de préparation et utilisation Download PDF

Info

Publication number
WO2022134408A1
WO2022134408A1 PCT/CN2021/089180 CN2021089180W WO2022134408A1 WO 2022134408 A1 WO2022134408 A1 WO 2022134408A1 CN 2021089180 W CN2021089180 W CN 2021089180W WO 2022134408 A1 WO2022134408 A1 WO 2022134408A1
Authority
WO
WIPO (PCT)
Prior art keywords
radioactive glass
radioactive
injection
glass microspheres
tumor
Prior art date
Application number
PCT/CN2021/089180
Other languages
English (en)
Chinese (zh)
Inventor
赵小生
马文亮
张驰翔
张钧
白冰
路静
刘强强
吴文轩
赵世强
柳芳
葛强
蔡继鸣
Original Assignee
成都纽瑞特医疗科技股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 成都纽瑞特医疗科技股份有限公司 filed Critical 成都纽瑞特医疗科技股份有限公司
Publication of WO2022134408A1 publication Critical patent/WO2022134408A1/fr

Links

Classifications

    • 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
    • A61K51/1213—Semi-solid forms, gels, hydrogels, ointments, fats and waxes that are solid at room temperature
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • 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
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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

Definitions

  • the invention relates to the technical field of medicine, in particular to a radioactive glass microsphere injection and a preparation method and application thereof.
  • the current clinically used radioactive microsphere products mainly include yttrium [ 90 Y] resin microspheres SIR-Spheres® (Sirtex Medical Limited, Australia) and yttrium [ 90 Y] glass microspheres TheraSphere® (BTG, UK) and are undergoing clinical trials.
  • the holmium [ 166 Ho] resin microspheres (QuriemSphere®) studied in the experiment, these three microsphere products are all radioactive microsphere products dispersed in sterile water for injection or 0.9% sodium chloride injection solution. The rapid sedimentation in the middle is prone to needle blockage, which makes it impossible for this type of product to be administered directly by a syringe.
  • the administration needs to use the perfusion administration device shown in Figure 1.
  • This administration method requires 20-60ml of injection solution for flushing and the radioactive microspheres along the The catheter is carried into the body.
  • This method can achieve better administration, it has obvious limitations. 1. It cannot be used for intratumoral administration due to the large administration volume and can only be used for intravascular administration; 2. It cannot be used according to the drug delivered to the body. The volume of the liquid is used to achieve the purpose of quantitative administration of the radioactive microspheres.
  • the density of glass microspheres is generally 2.0-3.0g/cm 3 .
  • some researchers use glycerol, 40% lipiodol, etc. as dispersion medium for radioactive glass microspheres. It is prepared as a suspension injection, and then administered to animals or humans by direct injection.
  • this method of using a high-viscosity dispersion medium can achieve the purpose of relatively uniformly dispersing the glass microspheres, this preparation also has several shortcomings: 1.
  • the viscosity of this type of injection generally exceeds 100mPa ⁇ S, and the high viscosity not only It makes the mixing process before injection difficult, and bubbles are easily wrapped in the injection during the mixing process and are not easy to remove; 2.
  • the injection process is also difficult to inject due to the large mass transfer resistance and the drug injected into the tissue is not easy to distribute evenly; 3.
  • the used The large amount of excipients increases the burden on metabolism and may bring safety risks; 4.
  • the mixed glass microspheres will settle to different degrees with the placement time; 5. It is difficult to dose the radioactive microspheres by the dosed volume. Make accurate calculations.
  • the present invention provides a radioactive glass microsphere injection and a preparation method and application, wherein the radioactive glass microsphere injection has low viscosity and good fluidity, and the radioactive glass microspheres are dispersed in a medium. It is uniform and does not settle for a long time, and can be used for direct injection.
  • the present invention also provides a radioactive glass microsphere injection.
  • the combination of sodium alginate and divalent metal ions to form a gel can not only disperse the glass microspheres uniformly, but also disperse the glass microspheres uniformly for a long time without sedimentation in the gel with the optimized formulation.
  • each 1 ml of the radioactive glass microsphere injection contains: 0.1-100 mg of radioactive glass microspheres, and 1-0.95 ml of hydrogel.
  • the glass microsphere injection can maintain good fluidity while ensuring that the glass microspheres do not settle, which can be achieved by direct injection. Dosing.
  • the viscosity of sodium alginate solution decreases significantly.
  • the viscosity of 0.2% sodium alginate solution is about 30 mPa ⁇ S.
  • the viscosity of the hydrogel is also different.
  • the mass ratio of sodium alginate to divalent metal ion is 1:0.05-0.15, the viscosity of the hydrogel formed is 5-20mPa ⁇ S.
  • the decrease in viscosity makes the resistance of the injection process smaller, the needle adaptability is better, the injection becomes easier, the air bubbles in the injection are easier to discharge, and more importantly, the viscosity decreases while the radioactive glass microspheres are in the hydrogel.
  • the dispersion becomes more uniform and the radioactive glass microspheres do not settle for a long time.
  • the mass ratio of the sodium alginate to the divalent metal ion is 1:(0.02-0.3), preferably 1:(0.05-0.15).
  • the viscosity of the hydrogel is between 1-100 mPa ⁇ S, preferably 5-20 mPa ⁇ S.
  • the divalent metal ion refers to a divalent metal ion with good biocompatibility, which can be combined with the sodium alginate solution to react instantaneously to form a hydrogel, such as calcium ion, strontium ion, preferably calcium ion.
  • the radionuclides loaded on the radioactive glass microspheres include but are not limited to: yttrium [ 90 Y], holmium [ 166 Ho], phosphorus [ 32 P], rhenium [ 186 Re], rhenium [ 188 Re], Any one or more of zirconium [ 89 Zr] and copper [ 64 Cu], these nuclides are supported on glass microspheres by any method to obtain radioactive glass microspheres.
  • the radioactive glass microsphere injection is macroscopically homogeneous, that is, an equal volume of the injection contains substantially the same amount of radioactive glass microspheres and radioactive dose. Therefore, accurate quantitative administration of the radioactive glass microspheres can be achieved by controlling the volume of the injection.
  • the dose of radioactivity contained in a unit volume can be adjusted within the range of 0-5GBq/ml, but when the radioactivity dose of the radioactive glass microspheres exceeds 5GBq/ml, the hydrogel undergoes radiation degradation in a short time, which makes the The viscosity of the composition dropped significantly and the homogeneity was destroyed.
  • the radioactivity of the radioactive glass microspheres is 0-5 GBq per milliliter of the injection, so that the radioactive concentration of the radioactive glass microspheres can be adjusted within a certain range.
  • the particles of the radioactive glass microspheres with a particle size of less than 1 ⁇ m can be uniformly and stably dispersed in the aqueous solution of the macromolecular suspending agent such as sodium carboxymethyl cellulose, while the particles with a particle size of 1-1000 ⁇ m in the ordinary high Molecular suspending agent solution cannot be uniformly and stably dispersed for a long time, but can be uniformly and stably dispersed for a long time in calcium alginate hydrogel.
  • the particle size of glass microspheres is larger than 300 ⁇ m, it is difficult to be administered by direct injection, and the particles with particle size less than 20 ⁇ m are easy to migrate to other tissues and organs in vivo.
  • the particle size of the radioactive glass microspheres is 1-1000 ⁇ m, preferably 20-300 ⁇ m, so that the radioactive glass microspheres are uniformly dispersed in the hydrogel system.
  • radioactive glass microspheres prepared by different materials can be stable in calcium alginate hydrogel. , evenly dispersed.
  • the radioactive glass microspheres comprise radioactive glass microspheres prepared by any method, including but not limited to: yttrium [ 90 Y] glass microspheres, holmium [ 166 Ho] glass microspheres, phosphorous [ 32 P] glass microspheres Any one or more of microspheres, rhenium [ 186 Re/ 188 Re] glass microspheres, zirconium [ 89 Zr] glass microspheres, and copper [ 64 Cu] glass microspheres.
  • the present invention also provides a method for preparing a radioactive glass microsphere injection, including the following two preparation methods:
  • the radioactive glass microspheres and the hydrogel are directly mixed uniformly, and the specific steps include:
  • the radioactive glass microsphere solution containing divalent metal ions and the sodium alginate solution are uniformly mixed, and the specific steps include:
  • the filter membrane is preferably a sterile filter membrane with a pore size of 0.22 ⁇ m.
  • the present invention When the present invention is in use, it is preferable to package the A1 agent and the B1 agent together, or to send the A2 agent and the B2 agent combined package as a complete set of products to the hospital to be mixed and formulated by the hospital before use.
  • the method of the second aspect of the present invention is a method of preparing the radioactive glass microsphere injection of the first aspect of the present invention.
  • the present invention also provides the radioactive glass microsphere injection according to the first aspect of the present invention and the radioactive glass microsphere injection prepared by the method according to the second aspect of the present invention, which are used in the preparation of the tumor treatment. application in medicine.
  • the tumors include, but are not limited to, solid tumors such as pancreatic cancer, liver cancer, breast cancer, and prostate cancer.
  • the drug contains radioactive glass microspheres and hydrogels.
  • the medicine comprises sodium alginate and radioactive glass microspheres containing divalent metal ions.
  • the calcium alginate hydrogel of the present invention and the calcium ions in the tumor tissue can further react to generate calcium alginate gel.
  • the calcium alginate gel is different from the hydrogel, and its viscosity is much larger than that of the hydrogel. It has no fluidity in the tissue, and it is not easy to move in the tissue after being fixed. This method is beneficial for the radioactive glass microsphere product to be fixed in the solid tumor and not easily transferred to other tissues and organs, which can further reduce the potential safety risk of the radioactive glass microsphere product during the treatment process.
  • the radioactive glass microsphere injection of the present invention can be administered by direct injection, or can be administered by injection after intervention by a puncture needle.
  • the drug when the tumor is a superficial or superficial tumor, the drug is administered intralesional by direct injection; while deep solid tumors such as pancreatic cancer, liver cancer, and glioma can be guided by ultrasound Under the puncture needle intervention or under the guidance of endoscopic ultrasonography for intratumoral injection.
  • the killing and killing of solid tumors are achieved by local high-dose radioactive radiation to achieve tumor treatment.
  • the drug can be used for local direct injection of the tumor, and after the drug reaches the lesion site, it can react with calcium ions in the tissue fluid to form a gel, so that the hydrogel gradually loses its fluidity, which is beneficial to fix the radioactive glass microspheres on the site. and reduce the toxic and side effects to other tissues or organs during local radiotherapy.
  • the present invention has the following beneficial effects:
  • the present invention significantly reduces the viscosity of the sodium alginate solution by preparing the sodium alginate solution into a hydrogel, so that the injection is not easy to generate bubbles or the bubbles are easily discharged, and the needle adaptability is improved while improving the radioactive glass microspheres in the liquid medium.
  • the dispersion is uniform and does not settle in the liquid phase for a long time.
  • the purpose of fixing the radioactive glass microspheres in the tumor is achieved through the further in situ gelation of the hydrogel in the tumor.
  • the safety risk of its clinical use is reduced.
  • the radioactive glass microspheres of the present invention are used to prepare a drug for treating tumors, the drug is directly injected into the tumor, and the drug can react with calcium ions in the tissue fluid after reaching the lesion site to form a gel, so that the hydrogel gradually loses
  • the fluidity is beneficial to fix the radioactive glass microspheres at the lesion site and reduce the toxic and side effects to other tissues or organs during local radiotherapy.
  • the radioactive glass microsphere injection of the present invention can significantly reduce the amount of excipients used and ensure the uniform dispersion of the glass microspheres.
  • the problem that the radioactive glass microspheres are not easy to be injected directly and the radioactive dose quantification cannot be directly performed by the administration volume during the administration of the radioactive glass microspheres is well solved.
  • Fig. 1 is the perfusion administration device of radioactive microspheres in the background technology
  • Figure 2 is a comparison diagram of the dispersion state when each sample is shaken up and left for 1min, 10min, 30min, and 60min in Example 11 of the present invention
  • Fig. 3 is a diagram of interventional administration under ultrasound guidance of an in situ model of rabbit liver cancer in Example 12 of the present invention.
  • a method for preparing yttrium [ 90 Y] glass microsphere injection comprising the following steps:
  • a method for preparing yttrium [ 90 Y] glass microsphere injection comprising the following steps:
  • a method for preparing a holmium [ 166 Ho] glass microsphere injection comprising the following steps:
  • a method for preparing phosphorus [ 32 P] glass microsphere injection comprising the following steps:
  • a method for preparing copper [ 64 Cu] glass microsphere injection comprises the following steps:
  • a method for preparing a zirconium [ 89 Zr] glass microsphere injection comprising the following steps:
  • a method for preparing an integrated rhenium [ 186 Re/ 188 Re] glass microsphere injection for diagnosis and treatment comprising the following steps:
  • a method for preparing an integrated radioactive glass microsphere injection for diagnosis and treatment comprising the following steps:
  • radioactive glass microsphere injections can also be obtained by the same or similar methods and processes described above, and will not be described one by one here.
  • Example 1 and Example 2 The injections in Example 1 and Example 2, as well as the radioactive glass microspheres dispersed in 25% glycerol solution, 50% glycerol solution, 75% glycerol solution, and various injections in glycerol, were sequentially administered by chicken tissue injection. During the administration process, the needle suitability was judged according to whether the injection was smooth and the glass microspheres remained on the needle. The results are shown in Table 1. During the test, it was found that the viscosity of 50% glycerol solution is about 55 mPa ⁇ S, which can be injected, but the radioactive glass microspheres will settle soon and cannot be administered smoothly.
  • Example 1 showed good needle adaptability.
  • the glass microspheres of the radioactive glass microsphere injection prepared in Example 1 and Example 2 are uniformly dispersed in the liquid medium and do not settle for a long time. The time for uniform dispersion without sedimentation all exceeded 2 hours. Glass microspheres dispersed in pure glycerol can also achieve long-term suspension of glass microspheres, but their viscosity exceeds 1200 mPa ⁇ S and cannot be injected through a syringe.
  • Ultrasound-guided interventional drug administration test was performed on 4 New Zealand rabbits with liver cancer orthotopic model; tumor size: 3.5-8.6 cm 3 ; dosing volume: 8% of the tumor volume, about 0.28-0.69 ml, radioactive
  • the amount of glass microspheres is about 2.8-6.9 mg/piece, and the activity of yttrium [ 89 Y] is about 0.03-0.07 mCi.
  • the tumor was localized and the puncture needle was inserted. When the puncture needle reached the target site, a certain volume of the injection in Example 2 was injected.
  • FIG. 3 is a diagram of the interventional drug delivery guided by ultrasound in an in situ model of rabbit liver cancer. In the figure, it can be seen that the obvious bright parts in the black circle are the radioactive glass microspheres after injection. The bright spots produced by the reflection prove that the drug was successfully injected into the tumor.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • Organic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une injection de microsphères de verre radioactives, une méthode de préparation et une utilisation. L'injection de microsphères de verre radioactives par 1 mL contient : 0,1 à 100 mg de microsphères de verre radioactives et 1 à 0,95 mL d'un hydrogel. L'injection est utilisée pour préparer un médicament pour traiter une tumeur, et peut être injectée directement dans la tumeur d'une manière interventionnelle, la dose radioactive des microsphères de verre radioactives est déterminée directement en fonction du volume d'administration, et l'hydrogel atteignant la tumeur peut former un gel dans la tumeur avec des ions calcium, ce qui permet de disperser et de définir plus uniformément les microsphères de verre radioactives dans la tumeur, de telle sorte que les microsphères de verre radioactives fournissent une radiothérapie locale à dose élevée pour obtenir le traitement de tumeurs solides, et l'injection présente de vastes perspectives d'application dans le traitement de tumeurs solides.
PCT/CN2021/089180 2020-12-23 2021-04-23 Injection de microsphères de verre radioactves, méthode de préparation et utilisation WO2022134408A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202011540590.9 2020-12-23
CN202011540590.9A CN114652865A (zh) 2020-12-23 2020-12-23 一种放射性玻璃微球注射剂及制备方法和用途

Publications (1)

Publication Number Publication Date
WO2022134408A1 true WO2022134408A1 (fr) 2022-06-30

Family

ID=82024447

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/089180 WO2022134408A1 (fr) 2020-12-23 2021-04-23 Injection de microsphères de verre radioactves, méthode de préparation et utilisation

Country Status (2)

Country Link
CN (1) CN114652865A (fr)
WO (1) WO2022134408A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116642876A (zh) * 2023-05-05 2023-08-25 北京先通国际医药科技股份有限公司 测定含钇玻璃微球中有关金属元素的含量的方法及其用途

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117263501A (zh) * 2023-10-07 2023-12-22 中国原子能科学研究院 含钇中空玻璃球的制备方法及应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4789501A (en) * 1984-11-19 1988-12-06 The Curators Of The University Of Missouri Glass microspheres
CN1080266A (zh) * 1993-04-23 1994-01-05 中国核动力研究设计院 医用磷32系列玻璃微球及其制备工艺
WO2002067998A2 (fr) * 2001-02-22 2002-09-06 Psimedica Limited Dispositifs et methodes de traitement du cancer

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005087274A1 (fr) * 2004-03-05 2005-09-22 Xl Sci-Tech, Inc. Materiaux pulverulents et compositions de radiotherapie
KR20170110574A (ko) * 2014-12-05 2017-10-11 오거스타 유니버시티 리서치 인스티튜트, 인크. 조직 보강, 생의학 및 화장품 적용을 위한 유리 복합체

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4789501A (en) * 1984-11-19 1988-12-06 The Curators Of The University Of Missouri Glass microspheres
CN1080266A (zh) * 1993-04-23 1994-01-05 中国核动力研究设计院 医用磷32系列玻璃微球及其制备工艺
WO2002067998A2 (fr) * 2001-02-22 2002-09-06 Psimedica Limited Dispositifs et methodes de traitement du cancer
US20200206372A1 (en) * 2001-02-22 2020-07-02 Oncosil Medical Ltd. Devices and methods for the treatment of cancer

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
HOLTE Ø, SKRETTING A, TØNNESEN H H, KARLSEN J: "the Norwegian Radium Hospital 2 Preparation of a radionuclide/gel formulation for localised radiotherapy to a wide range of organs and tissues", PHARMAZIE, vol. 61, no. 5, 1 May 2005 (2005-05-01), pages 420 - 425, XP055946755 *
HOLTE, ØYVINDA; SKRETTING, ARNEB; BACH-GANSMO, TOREC; HOL, PER KRISTIAND; JOHNSRUD, KJERSTIC; TØNNESEN, HANNE HJORTHA; KARLSEN, JA: "Localized internal radiotherapy with 90Y particles embedded in a new thermosetting alginate gel: A feasibility study in pigs,", NUCLEAR MEDICINE COMMUNICATIONS, vol. 27, no. 2, 31 December 2006 (2006-12-31), pages 185 - 190, XP009537747, ISSN: 0143-3636, DOI: 10.1097/01.mnm.0000194398.97195.d9 *
MASAKAZU KAWASHITA ; NAOKO MATSUI ; ZHIXIA LI ; TOSHIKI MIYAZAKI: "Preparation of porous yttrium oxide microparticles by gelation of ammonium alginate in aqueous solution containing yttrium ions", JOURNAL OF MATERIALS SCIENCE: MATERIALS IN MEDICINE, vol. 21, no. 6, 16 March 2010 (2010-03-16), Bo , pages 1837 - 1843, XP019822085, ISSN: 1573-4838 *
PENG CHENG-LIANG, SHIH YING-HSIA, LIN XI-ZHANG, YEH CHUNG-HSIN, SHIEH MING-JIUM, LIN WUU-JYH, LUO TSAI-YUEH: "Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma", INTERNATIONAL JOURNAL OF NANOMEDICINE, vol. 9, 1 January 2014 (2014-01-01), pages 4191 - 4201, XP055946759, DOI: 10.2147/IJN.S66346 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116642876A (zh) * 2023-05-05 2023-08-25 北京先通国际医药科技股份有限公司 测定含钇玻璃微球中有关金属元素的含量的方法及其用途

Also Published As

Publication number Publication date
CN114652865A (zh) 2022-06-24

Similar Documents

Publication Publication Date Title
US20200030077A1 (en) Embolization particulates for occluding a blood vessel
US10548996B2 (en) Hydrogels for localized radiotherapy
WO2022134408A1 (fr) Injection de microsphères de verre radioactves, méthode de préparation et utilisation
CN106334213B (zh) 一种血管栓塞材料、其制备方法及在药物制备中的用途
CN102309458B (zh) 海藻酸钠交联莫西沙星缓释微球、其制备方法和用途以及含有所述微球的血管靶向栓塞剂
CN101583366B (zh) 放射增敏剂或抗癌化学疗法增敏剂
CN104382918B (zh) 一种用于肿瘤局部注射的阿霉素脂质体温敏凝胶
CN113018463B (zh) 一种含放射性核素的医用天然高分子微球及其制备方法和用途
Wu et al. Near-infrared light-responsive hybrid hydrogels for the synergistic chemo-photothermal therapy of oral cancer
WO2022041803A1 (fr) Microsphère de carbone radioactif visualisée, et procédé de préparation et application associés
Zhang et al. Dual-phase injectable thermosensitive hydrogel incorporating Fe3O4@ PDA with pH and NIR triggered drug release for synergistic tumor therapy
CN104721131B (zh) 一种用于肿瘤原位治疗的凝胶制剂及制备方法
Abbaszadeh et al. A photoactive injectable antibacterial hydrogel to support chemo-immunotherapeutic effect of antigenic cell membrane and sorafenib by near-infrared light mediated tumor ablation
WO2022134409A1 (fr) Injection de microsphères de résine radioactive, procédé de préparation et utilisation
WO2022134407A1 (fr) Injection de microsphères de carbone radioactif, procédé de préparation et utilisation
WO2022134410A1 (fr) Injection de microsphères de silicium radioactif, procédé de préparation et utilisation
Ren et al. GM-CSF-loaded nanoparticles for photothermal-assisted immunotherapy against orthotopic bladder cancer
CN114504661A (zh) 一种荷载177Lu的可降解高分子材料微球及其制备方法和应用
Huang et al. Investigation of the local delivery of an intelligent chitosan-based 188 Re thermosensitive in situ-forming hydrogel in an orthotopic hepatoma-bearing rat model
CN104324032A (zh) 抗结核药物三联复方微球血管靶向栓塞缓释剂及其制备方法和用途
CN102670611B (zh) 抗结核药物三联复方微球血管靶向栓塞缓释剂及其制备方法和用途
Harris et al. Preparation, characterization, and stability of new prostaglandin E2 gel for local administration
CN112451475B (zh) 一种用于治疗空洞型肺结核的长效缓释凝胶
KR100700418B1 (ko) 방사성물질-키토산 복합체를 함유하는 전립선암 치료용조성물 및 조성물 제조용 키트
CN105641704B (zh) 一种产泡聚乳酸羟基乙酸泡腾药物及制备方法和应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21908419

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21908419

Country of ref document: EP

Kind code of ref document: A1