CH677926A5 - - Google Patents

Download PDF

Info

Publication number: CH677926A5
Authority: CH; Switzerland
Prior art keywords: ciclosporin; iii; particle size; crystal form; practically
Prior art date: 1987-12-21

Application number

CH4687/88A

Other languages

German (de)

English (en)

Inventor

Danielle Dr Giron

Martin Dr List

Friedrich Dr Richter

Yasuyuki Uike

Hans Peter Dr Weber

Original Assignee

Sandoz Ag

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.)

1987-12-21

Filing date

1988-12-19

Publication date

1991-07-15

1988-12-19 Application filed by Sandoz Ag filed Critical Sandoz Ag

1991-07-15 Publication of CH677926A5 publication Critical patent/CH677926A5/de

Links

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 claims description 130
108010036949 Cyclosporine Proteins 0.000 claims description 130
229960001265 ciclosporin Drugs 0.000 claims description 130
239000000203 mixture Substances 0.000 claims description 67
239000002245 particle Substances 0.000 claims description 64
239000013078 crystal Substances 0.000 claims description 63
238000000034 method Methods 0.000 claims description 26
238000002360 preparation method Methods 0.000 claims description 26
229930182912 cyclosporin Natural products 0.000 claims description 23
230000000699 topical effect Effects 0.000 claims description 21
239000007924 injection Substances 0.000 claims description 20
238000002347 injection Methods 0.000 claims description 20
229930105110 Cyclosporin A Natural products 0.000 claims description 19
230000008569 process Effects 0.000 claims description 15
239000008194 pharmaceutical composition Substances 0.000 claims description 13
239000004480 active ingredient Substances 0.000 claims description 10
238000002441 X-ray diffraction Methods 0.000 claims description 9
239000002904 solvent Substances 0.000 claims description 8
239000000463 material Substances 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 4
229940125721 immunosuppressive agent Drugs 0.000 claims description 3
239000003018 immunosuppressive agent Substances 0.000 claims description 3
239000002260 anti-inflammatory agent Substances 0.000 claims description 2
229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
230000009969 flowable effect Effects 0.000 claims description 2
230000001506 immunosuppresive effect Effects 0.000 claims description 2
238000001802 infusion Methods 0.000 claims description 2
239000013080 microcrystalline material Substances 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
239000000499 gel Substances 0.000 description 18
229920001223 polyethylene glycol Polymers 0.000 description 17
201000004681 Psoriasis Diseases 0.000 description 14
238000012986 modification Methods 0.000 description 14
230000004048 modification Effects 0.000 description 14
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
239000000243 solution Substances 0.000 description 13
239000006071 cream Substances 0.000 description 12
239000000047 product Substances 0.000 description 12
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 10
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 10
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
239000002202 Polyethylene glycol Substances 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000013081 microcrystal Substances 0.000 description 9
238000002425 crystallisation Methods 0.000 description 8
230000008025 crystallization Effects 0.000 description 8
229940068886 polyethylene glycol 300 Drugs 0.000 description 8
230000002500 effect on skin Effects 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000007788 liquid Substances 0.000 description 7
238000004519 manufacturing process Methods 0.000 description 7
239000002674 ointment Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
201000010099 disease Diseases 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
239000007903 gelatin capsule Substances 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
239000006186 oral dosage form Substances 0.000 description 6
239000008389 polyethoxylated castor oil Substances 0.000 description 6
239000012453 solvate Substances 0.000 description 6
239000003381 stabilizer Substances 0.000 description 6
108010010803 Gelatin Proteins 0.000 description 5
239000004599 antimicrobial Substances 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
238000009472 formulation Methods 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
235000011187 glycerol Nutrition 0.000 description 5
238000000227 grinding Methods 0.000 description 5
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 5
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 5
229960002216 methylparaben Drugs 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 5
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 5
229960003415 propylparaben Drugs 0.000 description 5
239000007787 solid Substances 0.000 description 5
239000004094 surface-active agent Substances 0.000 description 5
OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000000969 carrier Substances 0.000 description 4
239000000470 constituent Substances 0.000 description 4
238000009826 distribution Methods 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
239000008187 granular material Substances 0.000 description 4
238000000265 homogenisation Methods 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
238000010899 nucleation Methods 0.000 description 4
230000006911 nucleation Effects 0.000 description 4
QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 4
239000003826 tablet Substances 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
235000019445 benzyl alcohol Nutrition 0.000 description 3
238000001816 cooling Methods 0.000 description 3
RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 description 3
230000001419 dependent effect Effects 0.000 description 3
239000003995 emulsifying agent Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
-1 polyoxyethylene Polymers 0.000 description 3
229920000136 polysorbate Polymers 0.000 description 3
239000000843 powder Substances 0.000 description 3
208000017520 skin disease Diseases 0.000 description 3
238000000527 sonication Methods 0.000 description 3
238000005809 transesterification reaction Methods 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 2
206010003645 Atopy Diseases 0.000 description 2
208000009137 Behcet syndrome Diseases 0.000 description 2
206010048768 Dermatosis Diseases 0.000 description 2
208000003556 Dry Eye Syndromes Diseases 0.000 description 2
206010013774 Dry eye Diseases 0.000 description 2
208000009319 Keratoconjunctivitis Sicca Diseases 0.000 description 2
229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
230000008859 change Effects 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
239000000084 colloidal system Substances 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
230000036576 dermal application Effects 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000003889 eye drop Substances 0.000 description 2
229940012356 eye drops Drugs 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
239000012051 hydrophobic carrier Substances 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
230000036512 infertility Effects 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
239000007927 intramuscular injection Substances 0.000 description 2
239000006072 paste Substances 0.000 description 2
235000019271 petrolatum Nutrition 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
229920001281 polyalkylene Polymers 0.000 description 2
229920001515 polyalkylene glycol Polymers 0.000 description 2
229920005862 polyol Polymers 0.000 description 2
150000003077 polyols Chemical class 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
229920001451 polypropylene glycol Polymers 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000007929 subcutaneous injection Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
150000003626 triacylglycerols Chemical class 0.000 description 2
239000003871 white petrolatum Substances 0.000 description 2
JVKUCNQGESRUCL-UHFFFAOYSA-N 2-Hydroxyethyl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OCCO JVKUCNQGESRUCL-UHFFFAOYSA-N 0.000 description 1
OFQCQIGMURIECL-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]-2',6'-dimethylspiro[isoquinoline-4,4'-oxane]-1,3-dione;phosphoric acid Chemical compound OP(O)(O)=O.O=C1N(CCN(CC)CC)C(=O)C2=CC=CC=C2C21CC(C)OC(C)C2 OFQCQIGMURIECL-UHFFFAOYSA-N 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
206010010741 Conjunctivitis Diseases 0.000 description 1
206010012438 Dermatitis atopic Diseases 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
239000004606 Fillers/Extenders Substances 0.000 description 1
208000012659 Joint disease Diseases 0.000 description 1
229920003102 Methocel™ E4M Polymers 0.000 description 1
235000019482 Palm oil Nutrition 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
108010002885 Polygeline Proteins 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
229920001304 Solutol HS 15 Polymers 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
206010046851 Uveitis Diseases 0.000 description 1
230000009471 action Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
208000002205 allergic conjunctivitis Diseases 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000002917 arthritic effect Effects 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
229920003086 cellulose ether Polymers 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
238000011161 development Methods 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000006196 drop Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
239000008394 flocculating agent Substances 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
239000012263 liquid product Substances 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
235000014571 nuts Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000002540 palm oil Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
238000010951 particle size reduction Methods 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
239000000902 placebo Substances 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
229940093430 polyethylene glycol 1500 Drugs 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
229950008882 polysorbate Drugs 0.000 description 1
229940113124 polysorbate 60 Drugs 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000010298 pulverizing process Methods 0.000 description 1
238000003127 radioimmunoassay Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000007670 refining Methods 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
238000009210 therapy by ultrasound Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Immunology (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Dermatology (AREA)
Epidemiology (AREA)
Transplantation (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Peptides Or Proteins (AREA)

CH4687/88A 1987-12-21 1988-12-19 CH677926A5 (da)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date
US13623087A	1987-12-21	1987-12-21
US17261388A	1988-03-24	1988-03-24
US21254888A	1988-06-28	1988-06-28

Publications (1)

Publication Number	Publication Date
CH677926A5 true CH677926A5 (da)	1991-07-15

Family

ID=27384838

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH4687/88A CH677926A5 (da)	1987-12-21	1988-12-19

Country Status (27)

Country	Link
JP (1)	JPH0791316B2 (da)
KR (1)	KR100188305B1 (da)
AT (1)	AT403163B (da)
AU (1)	AU626274B2 (da)
BE (1)	BE1002665A4 (da)
CA (1)	CA1341396C (da)
CH (1)	CH677926A5 (da)
CY (1)	CY1799A (da)
DE (1)	DE3843054C2 (da)
DK (1)	DK175220B1 (da)
ES (1)	ES2012580A6 (da)
FI (1)	FI89065C (da)
FR (1)	FR2624863B1 (da)
GB (1)	GB2211848B (da)
GR (1)	GR1002486B (da)
HK (1)	HK102894A (da)
HU (1)	HU203564B (da)
IE (1)	IE62006B1 (da)
IL (1)	IL88719A0 (da)
IT (1)	IT1235356B (da)
LU (1)	LU87409A1 (da)
MY (1)	MY103943A (da)
NL (1)	NL195096C (da)
NO (1)	NO177228C (da)
NZ (1)	NZ227384A (da)
SE (1)	SE503174C2 (da)
SG (1)	SG99494G (da)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5639724A (en)	1984-07-24	1997-06-17	Sandoz Ltd.	Cyclosporin galenic forms
US6007840A (en) *	1988-09-16	1999-12-28	Novartis Ag	Pharmaceutical compositions comprising cyclosporins
KR0148748B1 (ko) *	1988-09-16	1998-08-17	장 크라메르, 한스 루돌프 하우스	사이클로스포린을 함유하는 약학조성물
US7081445B2 (en)	1989-02-20	2006-07-25	Novartis Ag	Cyclosporin galenic forms
US5294604A (en) *	1989-12-20	1994-03-15	The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services	Method of treating ocular diseases by periocular administration of cyclosporine A or G
GB9105705D0 (en) *	1991-03-18	1991-05-01	Sandoz Ltd	Improvements in or relating to organic compounds
US6262022B1 (en)	1992-06-25	2001-07-17	Novartis Ag	Pharmaceutical compositions containing cyclosporin as the active agent
SG45449A1 (en) *	1992-05-13	1998-01-16	Sandoz Ltd	Ophthalmic compositions
DK0589843T3 (da)	1992-09-25	2002-04-02	Novartis Ag	Cyclosporinholdige farmaceutiske præparater
ES2177652T3 (es)	1994-11-03	2002-12-16	Novartis Ag	Nuevas formas de preparacion de ciclosporina para la aplicacion oral con composicion simple y alta biodisponibilidad, y procedimiento para su obtencion.
US5962019A (en) *	1995-08-25	1999-10-05	Sangstat Medical Corporation	Oral cyclosporin formulations
US5766629A (en)	1995-08-25	1998-06-16	Sangstat Medical Corporation	Oral cyclosporin formulations
DE19544507B4 (de)	1995-11-29	2007-11-15	Novartis Ag	Cyclosporin enthaltende Präparate
US6262054B1 (en)	1996-02-01	2001-07-17	Sloan-Kettering Institute Of Cancer Research	Combination therapy method for treating breast cancer using edatrexate
KR20050084502A (ko)	1997-01-30	2005-08-26	노파르티스 아게	오일을 함유하지 않은 사이클로스포린 ａ 함유 제약 조성물
TW581681B (en)	1998-02-20	2004-04-01	Nektar Therapeutics	Liquid crystal forms of cyclosporin
US7732404B2 (en)	1999-12-30	2010-06-08	Dexcel Ltd	Pro-nanodispersion for the delivery of cyclosporin
CN100548271C (zh)	2004-01-20	2009-10-14	阿勒根公司	用于眼部的局部治疗、并优选包括有曲安奈德及透明质酸的组合物
CN1763084B (zh) *	2005-10-11	2010-04-21	山东新时代药业有限公司	高纯度环孢菌素a的制备方法
BR112013030554B1 (pt) *	2011-05-27	2020-12-15	Allergan, Inc.	Forma cristalina de ciclosporina a, métodos de preparação e métodos para uso da mesma
RU2641963C2 (ru) *	2011-11-15	2018-01-23	Аллерган, Инк.	Взвеси циклоспорина а формы 2
US20130123194A1 (en) *	2011-11-15	2013-05-16	Allergan, Inc.	Autoclavable suspensions of cyclosporin a form 2
CA2856034C (en) *	2011-11-15	2017-12-12	Allergan, Inc.	Cyclosporin a form 2 and method of making same
US8785394B2 (en) *	2011-11-15	2014-07-22	Allergan, Inc.	Sustained action formulation of cyclosporin form 2
TW202430537A (zh) *	2022-10-20	2024-08-01	日商中外製藥股份有限公司	環狀胜肽的結晶的製造方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH614931A5 (da) *	1975-11-04	1979-12-28	Sandoz Ag
CH640519A5 (en) *	1976-04-09	1984-01-13	Sandoz Ag	Process for preparing a modified form of the antibiotic S 7481/F-1
US4117118A (en) *	1976-04-09	1978-09-26	Sandoz Ltd.	Organic compounds
DE2819094A1 (de) *	1977-05-10	1978-11-23	Sandoz Ag	Cyclosporin-derivate, ihre verwendung und herstellung
CH637124A5 (en) *	1978-10-18	1983-07-15	Sandoz Ag	Antibiotic, its preparation and use

1988
- 1988-12-09 HU HU886374A patent/HU203564B/hu unknown
- 1988-12-19 NO NO885625A patent/NO177228C/no unknown
- 1988-12-19 AU AU27055/88A patent/AU626274B2/en not_active Expired
- 1988-12-19 FI FI885869A patent/FI89065C/fi not_active IP Right Cessation
- 1988-12-19 IE IE377988A patent/IE62006B1/en not_active IP Right Cessation
- 1988-12-19 CH CH4687/88A patent/CH677926A5/de not_active IP Right Cessation
- 1988-12-19 SE SE8804570A patent/SE503174C2/sv not_active IP Right Cessation
- 1988-12-19 NZ NZ227384A patent/NZ227384A/xx unknown
- 1988-12-19 DK DK198807054A patent/DK175220B1/da not_active IP Right Cessation
- 1988-12-19 IL IL88719A patent/IL88719A0/xx unknown
- 1988-12-19 FR FR888816886A patent/FR2624863B1/fr not_active Expired - Lifetime
- 1988-12-19 GB GB8829556A patent/GB2211848B/en not_active Expired - Lifetime
- 1988-12-20 LU LU87409A patent/LU87409A1/fr unknown
- 1988-12-20 KR KR1019880017194A patent/KR100188305B1/ko not_active Expired - Lifetime
- 1988-12-20 IT IT8848690A patent/IT1235356B/it active
- 1988-12-20 BE BE8801421A patent/BE1002665A4/fr not_active IP Right Cessation
- 1988-12-20 JP JP63321857A patent/JPH0791316B2/ja not_active Expired - Lifetime
- 1988-12-20 AT AT0309588A patent/AT403163B/de not_active IP Right Cessation
- 1988-12-20 GR GR880100850A patent/GR1002486B/el not_active IP Right Cessation
- 1988-12-21 CA CA000586611A patent/CA1341396C/en not_active Expired - Fee Related
- 1988-12-21 DE DE3843054A patent/DE3843054C2/de not_active Expired - Lifetime
- 1988-12-21 NL NL8803125A patent/NL195096C/nl active Search and Examination
- 1988-12-21 ES ES8803887A patent/ES2012580A6/es not_active Expired - Lifetime
- 1988-12-21 MY MYPI88001495A patent/MY103943A/en unknown
1994
- 1994-07-21 SG SG99494A patent/SG99494G/en unknown
- 1994-09-22 HK HK102894A patent/HK102894A/xx not_active IP Right Cessation
1995
- 1995-02-17 CY CY179995A patent/CY1799A/en unknown

Also Published As

Publication number	Publication date
NZ227384A (en)	1991-09-25
DK705488A (da)	1989-06-22
LU87409A1 (fr)	1989-07-07
NL195096C (nl)	2004-02-09
DK175220B1 (da)	2004-07-12
JPH01211598A (ja)	1989-08-24
FR2624863A1 (fr)	1989-06-23
IT8848690A0 (it)	1988-12-20
SE8804570D0 (sv)	1988-12-19
KR100188305B1 (ko)	1999-06-01
BE1002665A4 (fr)	1991-04-30
GR1002486B (el)	1996-12-09
GR880100850A (el)	1994-03-31
MY103943A (en)	1993-10-30
HK102894A (en)	1994-09-30
IT1235356B (it)	1992-06-30
CY1799A (en)	1995-02-17
CA1341396C (en)	2002-11-05
NL8803125A (nl)	1989-07-17
AT403163B (de)	1997-11-25
ES2012580A6 (es)	1990-04-01
JPH0791316B2 (ja)	1995-10-04
FR2624863B1 (fr)	1991-04-26
NO885625D0 (no)	1988-12-19
GB2211848B (en)	1991-11-06
ATA309588A (de)	1997-04-15
FI885869A0 (fi)	1988-12-19
FI89065C (fi)	1993-09-30
SE8804570L (sv)	1989-06-22
DE3843054A1 (de)	1989-07-27
AU626274B2 (en)	1992-07-30
DK705488D0 (da)	1988-12-19
NO885625L (no)	1989-06-22
SE503174C2 (sv)	1996-04-15
IL88719A0 (en)	1989-07-31
IE62006B1 (en)	1994-12-14
AU2705588A (en)	1989-06-22
FI885869L (fi)	1989-06-22
FI89065B (fi)	1993-04-30
IE883779L (en)	1989-06-21
KR890009975A (ko)	1989-08-05
SG99494G (en)	1994-10-28
HUT49893A (en)	1989-11-28
NO177228B (no)	1995-05-02
DE3843054C2 (de)	2003-08-21
NO177228C (no)	1995-08-09
HU203564B (en)	1991-08-28
GB8829556D0 (en)	1989-02-08
GB2211848A (en)	1989-07-12

Legal Events

Date	Code	Title	Description
1997-05-15	PFA	Name/firm changed	Owner name: SANDOZ AG TRANSFER- NOVARTIS AG
2008-12-31	PL	Patent ceased

Publication	Publication Date	Title
DE3843054C2 (de)	2003-08-21	Ciclosporin in nicht solvatisierter orthorhombischer Kristallform, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zusammensetzung
AT403435B (de)	1998-02-25	Cyclosporin enthaltende pharmazeutische zusammensetzung
DE4003844B4 (de)	2007-09-20	Neue Cyclosporin enthaltende galenische Formulierungen
DE69914742T2 (de)	2004-11-25	Gegen hitzeeinwirkung geschützte mikropartikel und verfahren zur terminalen dampfsterilisation derselben
DE69414840T2 (de)	1999-04-22	Akzeptabele pharmazeutische zusammensetzung enthaltend einen alkohol und einen hydrophalischen wirkstoff
DE60027171T2 (de)	2007-01-04	Nanopartikelzusammensetzungen enthaltend amorphes cyclosporin und deren herstellungsverfahren und verwendungsverfahren
EP1073426B1 (de)	2004-03-03	Pharmazeutische ciclosporin-formulierung mit verbesserten biopharmazeutischen eigenschaften, erhöhter physikalischer qualität & stabilität sowie verfahren zur herstellung
DE69004372T2 (de)	1994-04-21	Verfahren zum Mikronisieren schwerlöslicher Arzneistoffe.
AT390372B (de)	1990-04-25	Verwendung von solarfiltern zur stabilisierung und verbesserung der hautvertraeglichkeit von benzoylperoxyd enthaltenden zubereitungen zur lokalen aknebehandlung
DE60120696T2 (de)	2007-06-14	Wasserverdünnte emulsion mit niedrigem emulgatorgehalt
DE3382587T2 (de)	1992-12-24	Injizierbares langwirkendes mikroteilchen-praeparat zur verabreichung entzuendungshemmender mittel.
EP1289502B1 (de)	2006-07-19	Mikroemulsion-prekonzentrat, mikroemulsion und verwendung einer zusammensetzung
DE60214876T2 (de)	2007-04-05	Arzneizusammensetzung bestehend aus mikronisiertem progesteron, verfahren zu ihrer herstellung und ihre verwendungen
DE69511539T2 (de)	2000-03-30	Eine cyclosporin enthaltende zubereitung und ein verfahren für ihre herstellung
DE60017296T2 (de)	2006-01-12	Stabile Emulsion,Verfahren zur Herstellung und Emulgiermittel
DE2757827A1 (de)	1978-07-06	Arzneipraeparate mit einem gehalt an einem isosorbid-loesungsmittelsystem
DE60018081T2 (de)	2006-01-05	Pharmazeutische zusammensetzungen zur oralen und topischen verabreichung
DE3713492C2 (da)	1993-01-21
DE2557615A1 (de)	1977-06-23	Neue niclosamid-suspensionsformulierungen
CH683672A5 (de)	1994-04-29	Wasserlösliche Monoester als Solubilisatoren für pharmakologische Wirkstoffe und pharmazeutische Hilfsstoffe.
DE60100389T2 (de)	2004-05-19	Fettlösliche Substanzen enthaltende Granulate und Verfahren zu ihrer Herstellung
DE2902863A1 (de)	1979-07-26	Waessriges gel zur anwendung im bindehautsack
DE3238800A1 (de)	1983-05-05	Mit (gamma)-cyclodextrin gebildete einschlusskomplexe von steroidverbindungen, verfahren zu ihrer herstellung und diese einschlusskomplexe enthaltende arzneimittelpraeparate
DE68914683T2 (de)	1994-10-27	Arzneimittelzusammensetzung für die schnelle verabreichung des aktiven bestandteils, der aus einer festen dispersion und einem oberflächenaktiven mittel besteht.
DE4038385C2 (de)	1998-09-17	Sitosterol und seine Glykoside mit verbesserter Bioverfügbarkeit