JP6535008B2 - ナノ粒子を含む医薬組成物、その調製及び使用 - Google Patents
ナノ粒子を含む医薬組成物、その調製及び使用 Download PDFInfo
- Publication number
- JP6535008B2 JP6535008B2 JP2016541402A JP2016541402A JP6535008B2 JP 6535008 B2 JP6535008 B2 JP 6535008B2 JP 2016541402 A JP2016541402 A JP 2016541402A JP 2016541402 A JP2016541402 A JP 2016541402A JP 6535008 B2 JP6535008 B2 JP 6535008B2
- Authority
- JP
- Japan
- Prior art keywords
- nanoparticles
- nanoparticle
- biocompatible
- pharmaceutical composition
- nanoparticle aggregates
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 239000002105 nanoparticle Substances 0.000 title claims description 380
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 29
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 37
- -1 polyethyleneoxy Polymers 0.000 claims description 21
- 229920001223 polyethylene glycol Polymers 0.000 claims description 20
- 238000009825 accumulation Methods 0.000 claims description 17
- 239000002245 particle Substances 0.000 claims description 17
- CJNBYAVZURUTKZ-UHFFFAOYSA-N hafnium(iv) oxide Chemical compound O=[Hf]=O CJNBYAVZURUTKZ-UHFFFAOYSA-N 0.000 claims description 13
- 230000005865 ionizing radiation Effects 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 239000012736 aqueous medium Substances 0.000 claims description 6
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 3
- YUYCVXFAYWRXLS-UHFFFAOYSA-N trimethoxysilane Chemical compound CO[SiH](OC)OC YUYCVXFAYWRXLS-UHFFFAOYSA-N 0.000 claims description 3
- 239000000725 suspension Substances 0.000 description 54
- 206010028980 Neoplasm Diseases 0.000 description 49
- 229910052751 metal Inorganic materials 0.000 description 32
- 239000000203 mixture Substances 0.000 description 29
- 239000002184 metal Substances 0.000 description 27
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 25
- 229910000077 silane Inorganic materials 0.000 description 25
- 229920001427 mPEG Polymers 0.000 description 24
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 24
- 239000000243 solution Substances 0.000 description 19
- 230000035508 accumulation Effects 0.000 description 16
- 229910010272 inorganic material Inorganic materials 0.000 description 16
- 239000011147 inorganic material Substances 0.000 description 16
- 229910000449 hafnium oxide Inorganic materials 0.000 description 15
- WIHZLLGSGQNAGK-UHFFFAOYSA-N hafnium(4+);oxygen(2-) Chemical compound [O-2].[O-2].[Hf+4] WIHZLLGSGQNAGK-UHFFFAOYSA-N 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- 239000007924 injection Substances 0.000 description 15
- 229920000642 polymer Polymers 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 14
- 239000011248 coating agent Substances 0.000 description 13
- 241000699660 Mus musculus Species 0.000 description 11
- 238000011580 nude mouse model Methods 0.000 description 11
- 238000001959 radiotherapy Methods 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 230000005855 radiation Effects 0.000 description 10
- 238000000576 coating method Methods 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000001361 intraarterial administration Methods 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 210000003462 vein Anatomy 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 6
- 238000002591 computed tomography Methods 0.000 description 6
- CMIHHWBVHJVIGI-UHFFFAOYSA-N gadolinium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Gd+3].[Gd+3] CMIHHWBVHJVIGI-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229920001577 copolymer Polymers 0.000 description 5
- 230000001747 exhibiting effect Effects 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- 150000002739 metals Chemical class 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 150000004763 sulfides Chemical class 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 229920000249 biocompatible polymer Polymers 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 238000002296 dynamic light scattering Methods 0.000 description 4
- 238000010894 electron beam technology Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000010931 gold Substances 0.000 description 4
- VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 description 4
- 238000001935 peptisation Methods 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 108010020346 Polyglutamic Acid Proteins 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 238000007306 functionalization reaction Methods 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 229910052735 hafnium Inorganic materials 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 238000010884 ion-beam technique Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 201000005249 lung adenocarcinoma Diseases 0.000 description 3
- 239000002082 metal nanoparticle Substances 0.000 description 3
- 231100000957 no side effect Toxicity 0.000 description 3
- 229920002643 polyglutamic acid Polymers 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- GUTLYIVDDKVIGB-OUBTZVSYSA-N Cobalt-60 Chemical compound [60Co] GUTLYIVDDKVIGB-OUBTZVSYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 238000002725 brachytherapy Methods 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 201000007455 central nervous system cancer Diseases 0.000 description 2
- 208000025997 central nervous system neoplasm Diseases 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- NLQFUUYNQFMIJW-UHFFFAOYSA-N dysprosium(iii) oxide Chemical compound O=[Dy]O[Dy]=O NLQFUUYNQFMIJW-UHFFFAOYSA-N 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- PLDDOISOJJCEMH-UHFFFAOYSA-N neodymium(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Nd+3].[Nd+3] PLDDOISOJJCEMH-UHFFFAOYSA-N 0.000 description 2
- 230000014207 opsonization Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 150000004804 polysaccharides Chemical class 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- FKTOIHSPIPYAPE-UHFFFAOYSA-N samarium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Sm+3].[Sm+3] FKTOIHSPIPYAPE-UHFFFAOYSA-N 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- ZIKATJAYWZUJPY-UHFFFAOYSA-N thulium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Tm+3].[Tm+3] ZIKATJAYWZUJPY-UHFFFAOYSA-N 0.000 description 2
- 230000036326 tumor accumulation Effects 0.000 description 2
- 229920001221 xylan Polymers 0.000 description 2
- 150000004823 xylans Chemical class 0.000 description 2
- FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 229920002498 Beta-glucan Polymers 0.000 description 1
- 229910015902 Bi 2 O 3 Inorganic materials 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- MBMLMWLHJBBADN-UHFFFAOYSA-N Ferrous sulfide Chemical compound [Fe]=S MBMLMWLHJBBADN-UHFFFAOYSA-N 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000941423 Grom virus Species 0.000 description 1
- 208000012766 Growth delay Diseases 0.000 description 1
- 229910052689 Holmium Inorganic materials 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 229910052765 Lutetium Inorganic materials 0.000 description 1
- 208000032271 Malignant tumor of penis Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
- 229910017493 Nd 2 O 3 Inorganic materials 0.000 description 1
- 229910052779 Neodymium Inorganic materials 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 239000004696 Poly ether ether ketone Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229910052777 Praseodymium Inorganic materials 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 229910052775 Thulium Inorganic materials 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 229910052769 Ytterbium Inorganic materials 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229910000416 bismuth oxide Inorganic materials 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- NNLOHLDVJGPUFR-UHFFFAOYSA-L calcium;3,4,5,6-tetrahydroxy-2-oxohexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(=O)C([O-])=O.OCC(O)C(O)C(O)C(=O)C([O-])=O NNLOHLDVJGPUFR-UHFFFAOYSA-L 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- TVFDJXOCXUVLDH-RNFDNDRNSA-N cesium-137 Chemical compound [137Cs] TVFDJXOCXUVLDH-RNFDNDRNSA-N 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000012191 childhood neoplasm Diseases 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- TYIXMATWDRGMPF-UHFFFAOYSA-N dibismuth;oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Bi+3].[Bi+3] TYIXMATWDRGMPF-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- KBQHZAAAGSGFKK-UHFFFAOYSA-N dysprosium atom Chemical compound [Dy] KBQHZAAAGSGFKK-UHFFFAOYSA-N 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000004993 emission spectroscopy Methods 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- ZXGIFJXRQHZCGJ-UHFFFAOYSA-N erbium(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Er+3].[Er+3] ZXGIFJXRQHZCGJ-UHFFFAOYSA-N 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 229910001940 europium oxide Inorganic materials 0.000 description 1
- AEBZCFFCDTZXHP-UHFFFAOYSA-N europium(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Eu+3].[Eu+3] AEBZCFFCDTZXHP-UHFFFAOYSA-N 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 208000028149 female reproductive system neoplasm Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229910001938 gadolinium oxide Inorganic materials 0.000 description 1
- 229940075613 gadolinium oxide Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 150000002313 glycerolipids Chemical class 0.000 description 1
- PDPJQWYGJJBYLF-UHFFFAOYSA-J hafnium tetrachloride Chemical compound Cl[Hf](Cl)(Cl)Cl PDPJQWYGJJBYLF-UHFFFAOYSA-J 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 description 1
- OWCYYNSBGXMRQN-UHFFFAOYSA-N holmium(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Ho+3].[Ho+3] OWCYYNSBGXMRQN-UHFFFAOYSA-N 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 238000009616 inductively coupled plasma Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- XMBWDFGMSWQBCA-YPZZEJLDSA-N iodane Chemical compound [125IH] XMBWDFGMSWQBCA-YPZZEJLDSA-N 0.000 description 1
- GKOZUEZYRPOHIO-IGMARMGPSA-N iridium-192 Chemical compound [192Ir] GKOZUEZYRPOHIO-IGMARMGPSA-N 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 229910052746 lanthanum Inorganic materials 0.000 description 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- OHSVLFRHMCKCQY-UHFFFAOYSA-N lutetium atom Chemical compound [Lu] OHSVLFRHMCKCQY-UHFFFAOYSA-N 0.000 description 1
- 229910003443 lutetium oxide Inorganic materials 0.000 description 1
- 208000029565 malignant colon neoplasm Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 101150111571 mreg gene Proteins 0.000 description 1
- OKPYIWASQZGASP-UHFFFAOYSA-N n-(2-hydroxypropyl)-2-methylprop-2-enamide Chemical compound CC(O)CNC(=O)C(C)=C OKPYIWASQZGASP-UHFFFAOYSA-N 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 229920005690 natural copolymer Polymers 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- QEFYFXOXNSNQGX-UHFFFAOYSA-N neodymium atom Chemical compound [Nd] QEFYFXOXNSNQGX-UHFFFAOYSA-N 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 210000004279 orbit Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- MPARYNQUYZOBJM-UHFFFAOYSA-N oxo(oxolutetiooxy)lutetium Chemical compound O=[Lu]O[Lu]=O MPARYNQUYZOBJM-UHFFFAOYSA-N 0.000 description 1
- DYIZHKNUQPHNJY-UHFFFAOYSA-N oxorhenium Chemical compound [Re]=O DYIZHKNUQPHNJY-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- UZLYXNNZYFBAQO-UHFFFAOYSA-N oxygen(2-);ytterbium(3+) Chemical compound [O-2].[O-2].[O-2].[Yb+3].[Yb+3] UZLYXNNZYFBAQO-UHFFFAOYSA-N 0.000 description 1
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-OIOBTWANSA-N palladium-103 Chemical compound [103Pd] KDLHZDBZIXYQEI-OIOBTWANSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000771 poly (alkylcyanoacrylate) Polymers 0.000 description 1
- 229920001562 poly(N-(2-hydroxypropyl)methacrylamide) Polymers 0.000 description 1
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 description 1
- 229920000962 poly(amidoamine) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002530 polyetherether ketone Polymers 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- PUDIUYLPXJFUGB-UHFFFAOYSA-N praseodymium atom Chemical compound [Pr] PUDIUYLPXJFUGB-UHFFFAOYSA-N 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000000574 retroperitoneal space Anatomy 0.000 description 1
- 229910003449 rhenium oxide Inorganic materials 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- KZUNJOHGWZRPMI-AKLPVKDBSA-N samarium-153 Chemical compound [153Sm] KZUNJOHGWZRPMI-AKLPVKDBSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- FSJWWSXPIWGYKC-UHFFFAOYSA-M silver;silver;sulfanide Chemical compound [SH-].[Ag].[Ag+] FSJWWSXPIWGYKC-UHFFFAOYSA-M 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- CIOAGBVUUVVLOB-OUBTZVSYSA-N strontium-89 Chemical compound [89Sr] CIOAGBVUUVVLOB-OUBTZVSYSA-N 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- SCRZPWWVSXWCMC-UHFFFAOYSA-N terbium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Tb+3].[Tb+3] SCRZPWWVSXWCMC-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- FRNOGLGSGLTDKL-UHFFFAOYSA-N thulium atom Chemical compound [Tm] FRNOGLGSGLTDKL-UHFFFAOYSA-N 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 208000024722 urethra neoplasm Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 1
- 238000000733 zeta-potential measurement Methods 0.000 description 1
- 229910001928 zirconium oxide Inorganic materials 0.000 description 1
Classifications
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/242—Gold; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/244—Lanthanides; Compounds thereof
-
- 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
- A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1092—Details
- A61N2005/1098—Enhancing the effect of the particle by an injected agent or implanted device
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Ceramic Engineering (AREA)
- Dispersion Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
ナノ医療の欧州技術プラットフォームによれば、ナノ医療は、「ナノテクノロジーの健康への適用。ナノ医療は、ナノメートル単位の材料の改善された、そして、多くの場合新規の、物理的特性、化学的特性、そして、生物学的特性を活用する。ナノ医療は、疾患の予防、早期かつ信頼性のある診断、及び治療に対して潜在的な影響を有する。」と定義されている。
次に、本発明者らは、本明細書において、適切な用量域、すなわち、医師によって許容される、被験体に対する医薬組成物によって誘導される処置の許容し得るベネフィット/リスク比を保証する用量域で、標的部位、好ましくは、腫瘍部位にナノ粒子又はナノ粒子凝集体を系統的に送達することができる、該ナノ粒子又はナノ粒子凝集体を含む医薬組成物について開示する。
(式中、
− dは、表面1nm2当たりの分子数として表される、該ナノ粒子又はナノ粒子凝集体の各表面を被覆している少なくとも1種の生体適合性親水性ポリマーの緻密度であるか、又は少なくとも2種の異なるポリマーが該ナノ粒子又はナノ粒子凝集体の各表面を被覆しているとき、dは、最高分子量を示す生体適合性親水性ポリマーの緻密度であり、
− Mwは、キロダルトン(kDa)で表される、少なくとも1種の生体適合性親水性ポリマーの分子量であり、
− Cは、g/Lで表される、該医薬組成物中の該ナノ粒子又はナノ粒子凝集体の濃度である)
によって定義され、そして、該Accu Fが、体重1キログラム(kg)当たり該医薬組成物 少なくとも0.1gを該被験体に静脈内(IV)又は動脈内(IA)注射したとき、標的組織1グラム(g)当たりナノ粒子又はナノ粒子凝集体 少なくとも4ミリグラム(mg)の、該医薬組成物の該生体適合性のナノ粒子又はナノ粒子凝集体を該被験体の標的組織に蓄積させることができる生体適合性のナノ粒子又はナノ粒子凝集体を含む。
(式中、fnは、各元素に結合している電子の合計数の割合であり、そして、
Znは、各原子の原子番号である)。
である。
(式中、
− dは、表面1nm2当たりの分子数として表される、該ナノ粒子又はナノ粒子凝集体の各表面を被覆している少なくとも1種の生体適合性親水性ポリマーの緻密度であるか、又は少なくとも2種の異なるポリマーが該ナノ粒子又はナノ粒子凝集体の各表面を被覆しているとき、dは、最高分子量を示す生体適合性親水性ポリマーの緻密度であり、
− Mwは、キロダルトン(kDa)で表される、少なくとも1種の生体適合性親水性ポリマーの分子量であり、
− Cは、g/Lで表される、該医薬組成物中の該ナノ粒子又はナノ粒子凝集体の濃度である)
によって定義される生体適合性のナノ粒子又はナノ粒子凝集体を含む。
− 2〜50keVの超臨界X線:表面近傍のナノ粒子を励起(数ミリメートルの透過);
− 50〜150keVのX線:診断だけでなく治療にも;
− 6cmの厚さの組織を透過することができる200〜500keVのX線(正中電圧);
− 1000keV〜25,000keVのX線(超高圧)。
(式中、
− dは、表面1nm2当たりの分子数として表される、各ナノ粒子又はナノ粒子凝集体の表面を被覆している少なくとも1種の生体適合性親水性ポリマーの緻密度であるか、又は少なくとも2種の異なるポリマーが各ナノ粒子又はナノ粒子凝集体の表面を被覆しているとき、dは、最高分子量を示す生体適合性親水性ポリマーの緻密度であり、
− Mwは、キロダルトン(kDa)で表される、少なくとも1種の生体適合性親水性ポリマーの分子量(少なくとも2種の異なるポリマーが表面を被覆している場合、Mwは、最高分子量として選択される)であり、そして、
− Cは、g/Lで表される、医薬組成物中の該ナノ粒子又はナノ粒子凝集体の濃度である)。
実施例1:コーティング剤として2−[メトキシ(ポリエチレンオキシ)プロピル]トリエトキシシラン(mPEGシラン)10kDaを用いる、酸化ハフニウム(HfO2)のナノ粒子又はナノ粒子凝集体の生体適合性懸濁液。
テトラメチルアンモニウムヒドロキシド(TMAOH)溶液を塩化ハフニウム(HfCl4)溶液 40gに添加する。最終的な懸濁液のpHがpH7〜13に達するまで、TMAOH溶液の添加を実施する。白色の沈殿が得られる。沈殿を更にオートクレーブに移し、そして、120℃〜300℃の温度で加熱して、結晶化を実施する。冷却後、懸濁液を脱イオン水で洗浄する。
テトラメチルアンモニウムヒドロキシド(TMAOH)溶液をHfCl4溶液 40gに添加する。最終的な懸濁液のpHがpH7〜13に達するまで、TMAOH溶液の添加を実施する。白色の沈殿が得られる。沈殿を更にオートクレーブに移し、そして、120℃〜300℃の温度で加熱して、結晶化を実施する。冷却後、懸濁液を脱イオン水で洗浄する。
テトラメチルアンモニウムヒドロキシド(TMAOH)溶液をHfCl4溶液 40gに添加する。最終的な懸濁液のpHがpH7〜13に達するまで、TMAOH溶液の添加を実施する。白色の沈殿が得られる。沈殿を更にオートクレーブに移し、そして、120℃〜300℃の温度で加熱して、結晶化を実施する。冷却後、懸濁液を脱イオン水で洗浄する。
テトラメチルアンモニウムヒドロキシド(TMAOH)溶液をHfCl4溶液 40gに添加する。最終的な懸濁液のpHがpH7〜13に達するまで、TMAOH溶液の添加を実施する。白色の沈殿が得られる。沈殿を更にオートクレーブに移し、そして、120℃〜300℃の温度で加熱して、結晶化を実施する。冷却後、懸濁液を脱イオン水で洗浄する。
− ナノ粒子又はナノ粒子凝集体の表面1nm2当たりの分子数として表される、生体適合性親水性ポリマーの緻密度、又は少なくとも2種の異なるポリマーが各ナノ粒子又はナノ粒子凝集体の表面を被覆しているとき、最高分子量を示す生体適合性親水性ポリマーの緻密度;
− 生体適合性親水性ポリマーの分子量、又は少なくとも2種の異なるポリマーが表面を被覆している場合、最高分子量、及び
− g/Lで表される、医薬組成物中のナノ粒子又はナノ粒子凝集体の濃度。
生体適合性親水性ポリマー(mPEGシラン:2−[メトキシ(ポリエチレンオキシ)プロピル]トリエトキシシラン)で被覆されている酸化ハフニウム(HfO2)のナノ粒子又はナノ粒子凝集体の蓄積を、ヌードマウスにおける以下のヒト異種移植腫瘍モデルを用いて評価した:NCI-H460-luc2(ヒト非小細胞肺腺癌)、HT1080(ヒト線維肉腫)、MDA-MB-231(ヒト乳腺癌)、U87(ヒト多形性グリア芽細胞腫)、及びLPS80T3(脂肪肉腫患者の断片)。腫瘍異種移植ヌードマウスの尾静脈に10mL/kg ナノ粒子又はナノ粒子凝集体の生体適合性懸濁液を単回静脈内注射した。
様々な値のmREGシランの緻密度(d)、分子量(Mw)、及び濃度(C)を試験した。ICP-MSを用いて腫瘍内のハフニウム元素を定量することによって、ナノ粒子又はナノ粒子凝集体の懸濁液を静脈内注射した少なくとも24時間後のナノ粒子又はナノ粒子凝集体の腫瘍蓄積を評価した。少なくとも2つの異なるmPEGシランが各ナノ粒子又はナノ粒子凝集体の表面を被覆していた場合、dは、最高分子量を示す生体適合性親水性ポリマーの緻密度であり、そして、Mwは、最高分子量である。
実施例1のナノ粒子の懸濁液を尾静脈に単回注射(360g/Lに等しいナノ粒子又はナノ粒子凝集体濃度及び10mL/kgに等しい注射体積)した24時間後、NCI-H460-luc2(ヒト非小細胞肺腺癌)腫瘍(1群当たりn=5)において放射線(200kVp X線源を用いて10Gy)を単回照射した。腫瘍成長遅延曲線は、放射線療法のみ、すなわち、実施例1のHfO2のナノ粒子又はナノ粒子凝集体の生体適合性懸濁液の非存在下(対照群)で得られた効果と比べたとき、放射線療法で活性化されたNBTX-IVナノ粒子の顕著な抗腫瘍効果を示す(図2を参照)。副作用は観察されなかった。ナノ粒子又はナノ粒子凝集体は、腫瘍 1g当たりナノ粒子又はナノ粒子凝集体 4.1mgの濃度に対応する289794に等しい蓄積係数を有する(図1の点1)。
実施例4の酸化ハフニウムナノ粒子の生体適合性懸濁液を尾静脈に単回注射(360g/Lに等しいナノ粒子又はナノ粒子凝集体濃度及び10mL/kgに等しい注射体積)した後、4Gy 放射線を3回(200kVp X線源を用いて3×4Gy)、NCI-H460-luc2腫瘍(1群当たりn=5)に送達し、最初の線量は、酸化ハフニウム懸濁液の投与の24時間後に送達した。副作用は観察されなかった。放射線療法のみ、すなわち、実施例4のHfO2のナノ粒子又はナノ粒子凝集体の生体適合性懸濁液の非存在下(対照群)で得られた効果と比べたとき、放射線療法で活性化されたNBTX-IVナノ粒子の生存率では有意な差がみられた(P<0.005)(図3を参照)。ナノ粒子又はナノ粒子凝集体は、腫瘍 1g当たりナノ粒子又はナノ粒子凝集体 5.6mgの濃度に対応する409831に等しい蓄積係数を有する(図1の点2)。
実施例3の酸化ハフニウムナノ粒子の生体適合性懸濁液を尾静脈に単回注射(360g/Lに等しいナノ粒子又はナノ粒子凝集体濃度及び10mL/kgに等しい注射体積)した後、4Gy 放射線を3回(200kVp X線源を用いて3×4Gy)、NCI-H460-luc2腫瘍(1群当たりn=5)に送達し、最初の線量は、酸化ハフニウム懸濁液の投与の24時間後に送達した。副作用は観察されなかった。放射線療法のみ、すなわち、実施例3のHfO2のナノ粒子又はナノ粒子凝集体の生体適合性懸濁液の非存在下(対照群)で得られた効果と比べたとき、放射線療法で活性化されたNBTX-IVナノ粒子の生存率に差はみられなかった(図4を参照)。ナノ粒子又はナノ粒子凝集体は、腫瘍 1g当たりナノ粒子又はナノ粒子凝集体 2.4mgの濃度に対応する231836に等しい蓄積係数を有する(図1の点3)。
Claims (6)
- 生体適合性のナノ粒子又はナノ粒子凝集体を含む医薬組成物であって、i)該生体適合性のナノ粒子又はナノ粒子凝集体が、それぞれ、少なくとも1種の生体適合性親水性ポリマーで被覆されており、ii)該生体適合性のナノ粒子又はナノ粒子凝集体の各最長寸法が、50nm〜150nmであり、iii)pH6〜8の水性媒体中で測定したとき、該生体適合性のナノ粒子又はナノ粒子凝集体の各表面電荷値が、−15mV〜+15mVであり、そして、iv)該生体適合性のナノ粒子又はナノ粒子凝集体が、それを必要としている被験体に投与されたとき、該被験体の標的組織において少なくとも260500の蓄積係数(Accu F)を有し、該Accu Fが、以下の等式:
(式中、
− dは、表面1nm2当たりの分子数として表される、該ナノ粒子又はナノ粒子凝集体の各表面を被覆している少なくとも1種の生体適合性親水性ポリマーの緻密度であり、
− Mwは、キロダルトン(kDa)で表される、少なくとも1種の生体適合性親水性ポリマーの分子量であり、
− Cは、g/Lで表される、該医薬組成物中の該ナノ粒子又はナノ粒子凝集体の濃度である)
によって定義され、そして、該Accu Fが、体重1キログラム(kg)当たり該医薬組成物 少なくとも0.1gを該被験体に静脈内(IV)又は動脈内(IA)注射したとき、標的組織1グラム(g)当たり少なくとも4ミリグラム(mg)の、該医薬組成物の該生体適合性のナノ粒子又はナノ粒子凝集体を該被験体の標的組織に蓄積させることができ、
前記生体適合性のナノ粒子又はナノ粒子凝集体は、酸化ハフニウム(HfO 2 )のナノ粒子又は酸化ハフニウム(HfO 2 )のナノ粒子凝集体であり、
前記少なくとも1種の生体適合性親水性ポリマーが、アルコキシシラン官能化されたポリエチレングリコールである、医薬組成物。 - 生体適合性親水性ポリマーが、2−[メトキシ(ポリエチレンオキシ)プロピル]トリエトキシシラン又は2−[メトキシ(ポリエチレンオキシ)プロピル]トリメトキシシランである、請求項1記載の医薬組成物。
- dが、0.5〜8である、請求項2記載の医薬組成物。
- Mwが5kDa〜20kDaであり、そして、Cが350〜450g/Lである、請求項1〜3のいずれか一項記載の医薬組成物。
- 前記被験体の前記標的組織の細胞を電離放射線に曝露したとき、該細胞を変化させるか又は破壊するために使用する、請求項1〜4のいずれか一項記載の医薬組成物。
- 前記生体適合性のナノ粒子又はナノ粒子凝集体が、それぞれ、少なくとも2種の生体適合性親水性ポリマーで被覆され、そして、d及びMwが、それぞれ、少なくとも2種の生体適合性親水性ポリマーのうちの最高分子量を示す生体適合性親水性ポリマーの緻密度及び分子量である、請求項1〜5のいずれか一項記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP13306799.1 | 2013-12-20 | ||
EP13306799.1A EP2886128A1 (en) | 2013-12-20 | 2013-12-20 | Pharmaceutical composition comprising nanoparticles, preparation and uses thereof |
PCT/EP2014/078619 WO2015091888A1 (en) | 2013-12-20 | 2014-12-19 | Pharmaceutical composition comprising nanoparticles, preparation and uses thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017504603A JP2017504603A (ja) | 2017-02-09 |
JP6535008B2 true JP6535008B2 (ja) | 2019-06-26 |
Family
ID=49955847
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016541402A Active JP6535008B2 (ja) | 2013-12-20 | 2014-12-19 | ナノ粒子を含む医薬組成物、その調製及び使用 |
Country Status (4)
Country | Link |
---|---|
US (1) | US10265406B2 (ja) |
EP (2) | EP2886128A1 (ja) |
JP (1) | JP6535008B2 (ja) |
WO (1) | WO2015091888A1 (ja) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013087920A1 (en) | 2011-12-16 | 2013-06-20 | Nanobiotix | Nanoparticles comprising metallic and hafnium oxide materials, preparation and uses thereof |
WO2014191569A1 (en) | 2013-05-30 | 2014-12-04 | Nanobiotix | Pharmaceutical composition, preparation and uses thereof |
TW201628644A (zh) | 2014-11-25 | 2016-08-16 | 奈諾生技公司 | 醫藥組合物、其製備及其用途 |
BR112017010953B1 (pt) | 2014-11-25 | 2024-01-16 | Curadigm Sas | Composição farmacêutica contendo a combinação de um lipossoma e um carreador que compreende um composto farmacêutico |
HUE056175T2 (hu) | 2014-11-25 | 2022-01-28 | Curadigm Sas | Gyógyászati készítmények, elõállításuk és alkalmazásaik |
ES2951598T3 (es) | 2014-11-25 | 2023-10-23 | Curadigm Sas | Composición farmacéutica que combina al menos dos nanopartículas distintas y un compuesto farmacéutico, preparación y usos de los mismos |
CN107708668A (zh) | 2015-05-28 | 2018-02-16 | 纳米生物技术公司 | 用作治疗性疫苗的纳米粒子 |
ES2664584B2 (es) * | 2016-09-19 | 2018-12-13 | Universidade De Santiago De Compostela | Nanoparticulas con interiores protegidos, y métodos de uso de las mismas |
JP7469107B2 (ja) | 2020-03-31 | 2024-04-16 | 株式会社アルバック | 金ナノ粒子の凝集体、金ナノ粒子分散液、放射線治療用増感剤及び金ナノ粒子分散液の製造方法 |
US20230211175A1 (en) * | 2020-05-26 | 2023-07-06 | Nanobiotix S.A. | Nanoparticles, ionizing radiation and innovative therapeutic combinations thereof |
CN112957469A (zh) * | 2021-02-26 | 2021-06-15 | 广东药科大学 | pH响应性磁性纳米核壳载药体系及其构建方法和应用 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000006244A2 (en) * | 1998-07-30 | 2000-02-10 | Hainfeld James F | Loading metal particles into cell membrane vesicles and metal particle use for imaging and therapy |
WO2007122956A1 (ja) * | 2006-03-24 | 2007-11-01 | Toto Ltd. | 酸化チタン複合体粒子、その分散液、およびそれらの製造方法 |
IL181126A0 (en) | 2006-11-01 | 2007-07-04 | S B Biotechnologies Ltd | Preparation of gold-containing nano-liposome particles and their use in medical therapy |
FR2922106B1 (fr) | 2007-10-16 | 2011-07-01 | Univ Claude Bernard Lyon | Utilisation de nanoparticules a base de lanthanides comme agents radiosensibilisants. |
DE102008003615A1 (de) | 2008-01-09 | 2009-07-16 | Magforce Nanotechnologies Ag | Magnetische Transducer |
EP2130553A1 (en) * | 2008-06-05 | 2009-12-09 | Nanobiotix | Inorganic nanoparticles of high density to destroy cells in-vivo |
GB0921596D0 (en) * | 2009-12-09 | 2010-01-27 | Isis Innovation | Particles for the treatment of cancer in combination with radiotherapy |
EP2537530A4 (en) * | 2010-02-17 | 2015-12-16 | Nat Univ Corp Univ Kobe | RADIOTHERAPY AGENT |
US8592511B2 (en) | 2010-04-23 | 2013-11-26 | Pixelligent Technologies, Llc | Synthesis, capping and dispersion of nanocrystals |
US20130177523A1 (en) * | 2010-07-13 | 2013-07-11 | University Of Utah Research Foundation | Gold particles and methods of making and using the same in cancer treatment |
PL2948179T3 (pl) * | 2013-01-25 | 2019-10-31 | Nanobiotix | Kompozycje zawierające nanocząstki tlenku hafnu(iv) lub tlenku renu(iv) w połączeniu z promieniowaniem jonizującym do leczenia nowotworu |
-
2013
- 2013-12-20 EP EP13306799.1A patent/EP2886128A1/en not_active Withdrawn
-
2014
- 2014-12-19 JP JP2016541402A patent/JP6535008B2/ja active Active
- 2014-12-19 WO PCT/EP2014/078619 patent/WO2015091888A1/en active Application Filing
- 2014-12-19 US US15/105,046 patent/US10265406B2/en active Active
- 2014-12-19 EP EP14814896.8A patent/EP3082864A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
WO2015091888A1 (en) | 2015-06-25 |
EP2886128A1 (en) | 2015-06-24 |
EP3082864A1 (en) | 2016-10-26 |
JP2017504603A (ja) | 2017-02-09 |
US20160310614A1 (en) | 2016-10-27 |
US10265406B2 (en) | 2019-04-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6535008B2 (ja) | ナノ粒子を含む医薬組成物、その調製及び使用 | |
US8845507B2 (en) | Inorganic nanoparticles of high density to destroy cells in-vivo | |
JP6042450B2 (ja) | 金属材料および酸化ハフニウム材料を含むナノ粒子、その製造および使用 | |
US20170296661A1 (en) | Metallic nanoparticles, preparation and uses thereof | |
JP6619231B2 (ja) | 癌を治療するための電離放射線との併用での無機ナノ粒子組成物 | |
NZ625848B2 (en) | Nanoparticles comprising metallic and hafnium oxide materials, preparation and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171031 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180620 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180626 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180926 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190108 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190218 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190507 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190530 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6535008 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |