TWI267383B - Composition and method of preparing microparticles of water-insoluble substances - Google Patents
Composition and method of preparing microparticles of water-insoluble substances Download PDFInfo
- Publication number
- TWI267383B TWI267383B TW088105042A TW88105042A TWI267383B TW I267383 B TWI267383 B TW I267383B TW 088105042 A TW088105042 A TW 088105042A TW 88105042 A TW88105042 A TW 88105042A TW I267383 B TWI267383 B TW I267383B
- Authority
- TW
- Taiwan
- Prior art keywords
- particles
- phospholipid
- particle size
- charged
- water
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 14
- 239000011859 microparticle Substances 0.000 title claims description 10
- 239000000126 substance Substances 0.000 title description 2
- 239000002245 particle Substances 0.000 claims abstract description 89
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 40
- 239000003607 modifier Substances 0.000 claims abstract description 36
- 239000003814 drug Substances 0.000 claims abstract description 31
- 229940079593 drug Drugs 0.000 claims abstract description 30
- 229920001400 block copolymer Polymers 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000011105 stabilization Methods 0.000 claims abstract description 12
- 230000012010 growth Effects 0.000 claims abstract description 11
- 230000006641 stabilisation Effects 0.000 claims abstract description 11
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 230000002776 aggregation Effects 0.000 claims abstract description 6
- 238000009472 formulation Methods 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 8
- 229920001577 copolymer Polymers 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 239000003381 stabilizer Substances 0.000 claims description 8
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 150000002632 lipids Chemical class 0.000 claims description 6
- 230000005070 ripening Effects 0.000 claims description 6
- 238000005054 agglomeration Methods 0.000 claims description 4
- 230000004520 agglutination Effects 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 230000003068 static effect Effects 0.000 claims description 4
- 239000004519 grease Substances 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- 238000011049 filling Methods 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 239000000052 vinegar Substances 0.000 claims description 2
- 235000021419 vinegar Nutrition 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- 239000004593 Epoxy Substances 0.000 claims 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 2
- 239000005977 Ethylene Substances 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 230000002301 combined effect Effects 0.000 claims 2
- 150000002924 oxiranes Chemical class 0.000 claims 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims 2
- WSULSMOGMLRGKU-UHFFFAOYSA-N 1-bromooctadecane Chemical compound CCCCCCCCCCCCCCCCCCBr WSULSMOGMLRGKU-UHFFFAOYSA-N 0.000 claims 1
- XHQKASGOOUPDQN-UHFFFAOYSA-N 2,4-dioxabicyclo[1.1.0]butane Chemical compound O1C2OC21 XHQKASGOOUPDQN-UHFFFAOYSA-N 0.000 claims 1
- 206010013647 Drowning Diseases 0.000 claims 1
- 241000196324 Embryophyta Species 0.000 claims 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims 1
- 240000008866 Ziziphus nummularia Species 0.000 claims 1
- 210000000683 abdominal cavity Anatomy 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 150000001720 carbohydrates Chemical class 0.000 claims 1
- 239000007903 gelatin capsule Substances 0.000 claims 1
- 238000007689 inspection Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 239000007937 lozenge Substances 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- AMCPECLBZPXAPB-UHFFFAOYSA-N propane-1,2,3-triol;sodium Chemical compound [Na].OCC(O)CO AMCPECLBZPXAPB-UHFFFAOYSA-N 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 229910021653 sulphate ion Inorganic materials 0.000 claims 1
- 239000003643 water by type Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 238000004220 aggregation Methods 0.000 abstract description 3
- 238000005189 flocculation Methods 0.000 abstract description 2
- 230000016615 flocculation Effects 0.000 abstract description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 14
- 229930195725 Mannitol Natural products 0.000 description 13
- 239000000594 mannitol Substances 0.000 description 13
- 235000010355 mannitol Nutrition 0.000 description 13
- BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 description 11
- 238000003860 storage Methods 0.000 description 9
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 8
- 229930105110 Cyclosporin A Natural products 0.000 description 8
- 108010036949 Cyclosporine Proteins 0.000 description 8
- 229960001265 ciclosporin Drugs 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 229930182912 cyclosporin Natural products 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- 150000002009 diols Chemical class 0.000 description 6
- 230000008901 benefit Effects 0.000 description 4
- 238000010951 particle size reduction Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 3
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- -1 P 123 (Pfaastichl) Chemical class 0.000 description 2
- 229920002359 Tetronic® Polymers 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000005611 electricity Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- SLKDGVPOSSLUAI-PGUFJCEWSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCCCC SLKDGVPOSSLUAI-PGUFJCEWSA-N 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000010441 alabaster Substances 0.000 description 1
- 229940124325 anabolic agent Drugs 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000001022 anti-muscarinic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000012661 block copolymerization Methods 0.000 description 1
- RICLFGYGYQXUFH-UHFFFAOYSA-N buspirone hydrochloride Chemical compound [H+].[Cl-].C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 RICLFGYGYQXUFH-UHFFFAOYSA-N 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000005660 hydrophilic surface Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000005661 hydrophobic surface Effects 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/902—Specified use of nanostructure
- Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
- Y10S977/926—Topical chemical, e.g. cosmetic or sunscreen
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7980998P | 1998-03-30 | 1998-03-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TWI267383B true TWI267383B (en) | 2006-12-01 |
Family
ID=22152962
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW088105042A TWI267383B (en) | 1998-03-30 | 1999-05-14 | Composition and method of preparing microparticles of water-insoluble substances |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6387409B1 (enExample) |
| EP (1) | EP1067914B1 (enExample) |
| JP (2) | JP4709378B2 (enExample) |
| KR (1) | KR100628341B1 (enExample) |
| CN (1) | CN1303278B (enExample) |
| AT (1) | ATE318132T1 (enExample) |
| AU (1) | AU761205B2 (enExample) |
| CA (1) | CA2326456C (enExample) |
| DE (1) | DE69929959T2 (enExample) |
| ES (1) | ES2257041T3 (enExample) |
| IL (3) | IL138765A0 (enExample) |
| SE (1) | SE0003429L (enExample) |
| TW (1) | TWI267383B (enExample) |
| WO (1) | WO1999049846A2 (enExample) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7255877B2 (en) | 1996-08-22 | 2007-08-14 | Jagotec Ag | Fenofibrate microparticles |
| US6465016B2 (en) | 1996-08-22 | 2002-10-15 | Research Triangle Pharmaceuticals | Cyclosporiine particles |
| DE69929959T2 (de) * | 1998-03-30 | 2006-11-02 | Jagotec Ag | Zubereitungen enthaltend mikropartikel von wasserunlöslichen substanzen, sowie verfahren zu deren herstellung |
| US6979456B1 (en) | 1998-04-01 | 2005-12-27 | Jagotec Ag | Anticancer compositions |
| KR100635456B1 (ko) | 1998-05-29 | 2006-10-18 | 스키에파마 캐나다 인코포레이티드 | 열보호화 마이크로입자 조성물 및 그의 말단의 스팀멸균방법 |
| HK1042856B (zh) | 1998-11-20 | 2007-07-27 | Skyepharma Canada Inc. | 可分散的磷脂稳定的微粒 |
| CN1213733C (zh) * | 1998-11-20 | 2005-08-10 | 斯凯伊药品加拿大公司 | 制备稳定的不溶性微粒的悬浮液的方法 |
| DE60020382T2 (de) * | 1999-09-21 | 2006-01-26 | Skyepharma Canada Inc., Verdun | Oberflächenmodifizierte teilchenförmige zusammensetzungen biologisch aktiver stoffe |
| US7276249B2 (en) * | 2002-05-24 | 2007-10-02 | Elan Pharma International, Ltd. | Nanoparticulate fibrate formulations |
| US20080241070A1 (en) * | 2000-09-21 | 2008-10-02 | Elan Pharma International Ltd. | Fenofibrate dosage forms |
| US20030224058A1 (en) * | 2002-05-24 | 2003-12-04 | Elan Pharma International, Ltd. | Nanoparticulate fibrate formulations |
| US9700866B2 (en) | 2000-12-22 | 2017-07-11 | Baxter International Inc. | Surfactant systems for delivery of organic compounds |
| US6977085B2 (en) | 2000-12-22 | 2005-12-20 | Baxter International Inc. | Method for preparing submicron suspensions with polymorph control |
| US8067032B2 (en) | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
| US6607784B2 (en) | 2000-12-22 | 2003-08-19 | Baxter International Inc. | Microprecipitation method for preparing submicron suspensions |
| US6884436B2 (en) | 2000-12-22 | 2005-04-26 | Baxter International Inc. | Method for preparing submicron particle suspensions |
| US6951656B2 (en) | 2000-12-22 | 2005-10-04 | Baxter International Inc. | Microprecipitation method for preparing submicron suspensions |
| US7193084B2 (en) | 2000-12-22 | 2007-03-20 | Baxter International Inc. | Polymorphic form of itraconazole |
| US20030054042A1 (en) * | 2001-09-14 | 2003-03-20 | Elaine Liversidge | Stabilization of chemical compounds using nanoparticulate formulations |
| US20060003012A9 (en) | 2001-09-26 | 2006-01-05 | Sean Brynjelsen | Preparation of submicron solid particle suspensions by sonication of multiphase systems |
| CN1558755A (zh) | 2001-09-26 | 2004-12-29 | ���ع��ʹ�˾ | 通过分散和除去溶剂或液相制备亚微米大小的纳米颗粒 |
| US7112340B2 (en) | 2001-10-19 | 2006-09-26 | Baxter International Inc. | Compositions of and method for preparing stable particles in a frozen aqueous matrix |
| WO2003084518A2 (fr) | 2002-04-09 | 2003-10-16 | Flamel Technologies | Suspension orale de microcapsules de principes actifs |
| US20070264348A1 (en) * | 2002-05-24 | 2007-11-15 | Elan Pharma International, Ltd. | Nanoparticulate fibrate formulations |
| FR2842736B1 (fr) | 2002-07-26 | 2005-07-22 | Flamel Tech Sa | Formulation pharmaceutique orale sous forme d'une pluralite de microcapsules permettant la liberation prolongee de principe(s) actif(s) peu soluble(s) |
| FR2842735B1 (fr) | 2002-07-26 | 2006-01-06 | Flamel Tech Sa | Microcapsules a liberation modifiee de principes actifs peu solubles pour l'administration per os |
| CN1243538C (zh) * | 2002-11-21 | 2006-03-01 | 武汉利元亨药物技术有限公司 | 熊果酸豆磷脂纳米粒冻干粉针及制备方法 |
| GB0302672D0 (en) * | 2003-02-06 | 2003-03-12 | Astrazeneca Ab | Pharmaceutical formulations |
| US6931888B2 (en) * | 2003-02-07 | 2005-08-23 | Ferro Corporation | Lyophilization method and apparatus for producing particles |
| US20040178135A1 (en) * | 2003-03-13 | 2004-09-16 | Beplate Douglas K. | Filtering device incorporating nanoparticles |
| MXPA05012467A (es) * | 2003-05-19 | 2006-02-22 | Baxter Int | Particulas solidas que comprenden un anticonvulsivo o un inmunosupresor revestido con uno o mas modificadores de superficie. |
| EA200600877A1 (ru) * | 2003-10-31 | 2006-12-29 | Тева Фармасьютикал Индастриз, Лтд. | Наночастицы для доставки лекарств |
| US20070224278A1 (en) * | 2003-11-12 | 2007-09-27 | Lyons Robert T | Low immunogenicity corticosteroid compositions |
| US20060141049A1 (en) * | 2003-11-12 | 2006-06-29 | Allergan, Inc. | Triamcinolone compositions for intravitreal administration to treat ocular conditions |
| US20050250737A1 (en) * | 2003-11-12 | 2005-11-10 | Allergan, Inc. | Therapeutic ophthalmic compositions containing retinal friendly excipients and related methods |
| US20050101582A1 (en) | 2003-11-12 | 2005-05-12 | Allergan, Inc. | Compositions and methods for treating a posterior segment of an eye |
| WO2005072701A1 (en) | 2004-01-20 | 2005-08-11 | Allergan, Inc. | Compositions for localized therapy of the eye, comprising preferably triamcinolone acetonide and hyaluronic acid |
| US20050170063A1 (en) * | 2004-01-29 | 2005-08-04 | Lalit Chordia | Production of powder and viscous material |
| US8119154B2 (en) | 2004-04-30 | 2012-02-21 | Allergan, Inc. | Sustained release intraocular implants and related methods |
| US8147865B2 (en) | 2004-04-30 | 2012-04-03 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
| AU2005271700B2 (en) * | 2004-07-12 | 2010-11-11 | Allergan, Inc. | Opthalmic compositions and methods for treating ophthalmic conditions |
| WO2006057429A1 (ja) * | 2004-11-24 | 2006-06-01 | Nanocarrier Co., Ltd. | ブロックコポリマーのモーフォロジ－の変化方法 |
| BRPI0612071A2 (pt) * | 2005-06-14 | 2010-10-19 | Baxter Int | formulações farmacêuticas para minimizar interações entre fármacos |
| WO2007008697A2 (en) * | 2005-07-08 | 2007-01-18 | University Of Chicago | Compositions and methods for refolding of denatured proteins |
| WO2007059515A2 (en) * | 2005-11-15 | 2007-05-24 | Baxter International, Inc. | Compositions of lipoxygenase inhibitors |
| WO2008080047A2 (en) * | 2006-12-23 | 2008-07-03 | Baxter International Inc. | Magnetic separation of fine particles from compositions |
| US8722736B2 (en) * | 2007-05-22 | 2014-05-13 | Baxter International Inc. | Multi-dose concentrate esmolol with benzyl alcohol |
| US8426467B2 (en) * | 2007-05-22 | 2013-04-23 | Baxter International Inc. | Colored esmolol concentrate |
| US20080293814A1 (en) * | 2007-05-22 | 2008-11-27 | Deepak Tiwari | Concentrate esmolol |
| MX2010001311A (es) * | 2007-07-31 | 2010-04-21 | Otsuka Pharma Co Ltd | Metodo para producir una suspensi?n de aripiprazol y formulacion liofilizada. |
| EP2200613B1 (en) | 2007-09-21 | 2018-09-05 | The Johns Hopkins University | Phenazine derivatives and uses thereof |
| CN103228266B (zh) | 2010-10-29 | 2017-11-14 | 健康科学西部大学 | 三元混合物制剂 |
| WO2014004507A1 (en) * | 2012-06-27 | 2014-01-03 | Shell Oil Company | Fuel and engine oil composition and its use |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5091187A (en) | 1990-04-26 | 1992-02-25 | Haynes Duncan H | Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs |
| US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| MX9201782A (es) | 1991-04-19 | 1992-10-01 | Sandoz Ag | Particulas de sustancias biologicamente activas, sustancialmente insolubles en agua, proceso para su produccion y composicion farmaceutica que las contiene. |
| US5298262A (en) | 1992-12-04 | 1994-03-29 | Sterling Winthrop Inc. | Use of ionic cloud point modifiers to prevent particle aggregation during sterilization |
| US5340564A (en) | 1992-12-10 | 1994-08-23 | Sterling Winthrop Inc. | Formulations comprising olin 10-G to prevent particle aggregation and increase stability |
| US5336507A (en) | 1992-12-11 | 1994-08-09 | Sterling Winthrop Inc. | Use of charged phospholipids to reduce nanoparticle aggregation |
| US5326552A (en) | 1992-12-17 | 1994-07-05 | Sterling Winthrop Inc. | Formulations for nanoparticulate x-ray blood pool contrast agents using high molecular weight nonionic surfactants |
| DE4440337A1 (de) | 1994-11-11 | 1996-05-15 | Dds Drug Delivery Services Ges | Pharmazeutische Nanosuspensionen zur Arzneistoffapplikation als Systeme mit erhöhter Sättigungslöslichkeit und Lösungsgeschwindigkeit |
| US5569448A (en) | 1995-01-24 | 1996-10-29 | Nano Systems L.L.C. | Sulfated nonionic block copolymer surfactants as stabilizer coatings for nanoparticle compositions |
| ATE198148T1 (de) * | 1995-02-06 | 2001-01-15 | Elan Pharma Int Ltd | Formulierungen von verbindungen als nanopartikel dispergiert in verdaubaren ölen oder fettsäuren |
| US5510118A (en) | 1995-02-14 | 1996-04-23 | Nanosystems Llc | Process for preparing therapeutic compositions containing nanoparticles |
| WO1997014407A1 (en) * | 1995-10-17 | 1997-04-24 | Research Triangle Pharmaceuticals | Insoluble drug delivery |
| US5686133A (en) | 1996-01-31 | 1997-11-11 | Port Systems, L.L.C. | Water soluble pharmaceutical coating and method for producing coated pharmaceuticals |
| JP2000516244A (ja) * | 1996-08-22 | 2000-12-05 | リサーチ・トライアングル・ファーマシューティカルズ | 水不溶性物質の微粒子を含む組成物およびその製造方法 |
| WO1999029300A1 (en) * | 1997-12-10 | 1999-06-17 | Rtp Pharma Inc. | Self-emulsifying fenofibrate formulations |
| DE69929959T2 (de) * | 1998-03-30 | 2006-11-02 | Jagotec Ag | Zubereitungen enthaltend mikropartikel von wasserunlöslichen substanzen, sowie verfahren zu deren herstellung |
| KR20140029532A (ko) * | 2011-09-30 | 2014-03-10 | 제이엑스 닛코 닛세키 킨조쿠 가부시키가이샤 | 스퍼터링 타깃 및 그 제조 방법 |
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1999
- 1999-03-29 DE DE69929959T patent/DE69929959T2/de not_active Expired - Lifetime
- 1999-03-29 AT AT99912926T patent/ATE318132T1/de not_active IP Right Cessation
- 1999-03-29 KR KR1020007010469A patent/KR100628341B1/ko not_active Expired - Fee Related
- 1999-03-29 IL IL13876599A patent/IL138765A0/xx active IP Right Grant
- 1999-03-29 AU AU31185/99A patent/AU761205B2/en not_active Ceased
- 1999-03-29 ES ES99912926T patent/ES2257041T3/es not_active Expired - Lifetime
- 1999-03-29 JP JP2000540812A patent/JP4709378B2/ja not_active Expired - Fee Related
- 1999-03-29 WO PCT/US1999/006746 patent/WO1999049846A2/en not_active Ceased
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- 1999-03-29 EP EP99912926A patent/EP1067914B1/en not_active Expired - Lifetime
- 1999-03-29 IL IL16202399A patent/IL162023A0/xx unknown
- 1999-03-29 CN CN998067113A patent/CN1303278B/zh not_active Expired - Fee Related
- 1999-05-14 TW TW088105042A patent/TWI267383B/zh not_active IP Right Cessation
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- 2000-09-26 SE SE0003429A patent/SE0003429L/xx not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| CN1303278A (zh) | 2001-07-11 |
| IL138765A0 (en) | 2001-10-31 |
| ATE318132T1 (de) | 2006-03-15 |
| WO1999049846A3 (en) | 1999-11-18 |
| ES2257041T3 (es) | 2006-07-16 |
| CN1303278B (zh) | 2010-06-23 |
| KR100628341B1 (ko) | 2006-09-27 |
| JP2011037889A (ja) | 2011-02-24 |
| AU761205B2 (en) | 2003-05-29 |
| US6387409B1 (en) | 2002-05-14 |
| SE0003429L (sv) | 2000-11-23 |
| IL162023A0 (en) | 2005-11-20 |
| JP5539839B2 (ja) | 2014-07-02 |
| EP1067914A2 (en) | 2001-01-17 |
| JP2002509876A (ja) | 2002-04-02 |
| WO1999049846A2 (en) | 1999-10-07 |
| DE69929959D1 (de) | 2006-04-27 |
| DE69929959T2 (de) | 2006-11-02 |
| CA2326456C (en) | 2008-12-23 |
| IL138765A (en) | 2007-09-20 |
| JP4709378B2 (ja) | 2011-06-22 |
| SE0003429D0 (sv) | 2000-09-26 |
| AU3118599A (en) | 1999-10-18 |
| KR20010042103A (ko) | 2001-05-25 |
| CA2326456A1 (en) | 1999-10-07 |
| EP1067914B1 (en) | 2006-02-22 |
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