HRP950249A2 - Novel sin-1 cyclodextrin inclusion complexes - Google Patents

Novel sin-1 cyclodextrin inclusion complexes Download PDF

Info

Publication number: HRP950249A2
Authority: HR; Croatia
Prior art keywords: sin; cyclodextrin; inclusion complexes; complexes; indicated
Prior art date: 1994-04-26

Application number

HRP9401183A

Other languages

English (en)

Croatian (hr)

Inventor

Joseph Geczy

Andrasne Vikmon

Joszef Szejtli

Lajos Szente

Julianna Szeman

Original Assignee

Therabel Research Sa

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.)

1994-04-26

Filing date

1995-04-25

Publication date

1997-10-31

1995-04-25 Application filed by Therabel Research Sa filed Critical Therabel Research Sa

1997-10-31 Publication of HRP950249A2 publication Critical patent/HRP950249A2/hr

Links

NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 title claims abstract description 65
229920000858 Cyclodextrin Polymers 0.000 title claims abstract description 40
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 40
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims abstract description 51
238000000034 method Methods 0.000 claims abstract description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 27
-1 carboxylic acid anions Chemical class 0.000 claims abstract description 23
238000002360 preparation method Methods 0.000 claims abstract description 23
150000002500 ions Chemical class 0.000 claims abstract description 20
230000008569 process Effects 0.000 claims abstract description 18
239000003054 catalyst Substances 0.000 claims abstract description 16
230000015572 biosynthetic process Effects 0.000 claims abstract description 15
238000001035 drying Methods 0.000 claims abstract description 14
239000007787 solid Substances 0.000 claims abstract description 14
239000003381 stabilizer Substances 0.000 claims abstract description 12
229940097362 cyclodextrins Drugs 0.000 claims abstract description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims abstract description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 9
150000003839 salts Chemical class 0.000 claims abstract description 9
229910019142 PO4 Inorganic materials 0.000 claims abstract description 8
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 7
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims abstract description 7
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims abstract description 7
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims abstract description 7
238000004108 freeze drying Methods 0.000 claims abstract description 7
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims abstract description 6
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 6
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 6
239000010452 phosphate Substances 0.000 claims abstract description 6
150000001768 cations Chemical class 0.000 claims abstract description 5
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims abstract description 5
239000012736 aqueous medium Substances 0.000 claims abstract description 4
230000003197 catalytic effect Effects 0.000 claims abstract description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract 2
239000000243 solution Substances 0.000 claims description 21
239000000203 mixture Substances 0.000 claims description 14
150000001450 anions Chemical class 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 9
239000000843 powder Substances 0.000 claims description 8
238000004090 dissolution Methods 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
241001465754 Metazoa Species 0.000 claims description 5
230000001419 dependent effect Effects 0.000 claims description 5
150000007522 mineralic acids Chemical class 0.000 claims description 5
208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 5
208000024891 symptom Diseases 0.000 claims description 5
229940095064 tartrate Drugs 0.000 claims description 5
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
150000001447 alkali salts Chemical class 0.000 claims description 4
239000007864 aqueous solution Substances 0.000 claims description 4
229940079593 drug Drugs 0.000 claims description 4
238000009472 formulation Methods 0.000 claims description 4
239000004615 ingredient Substances 0.000 claims description 4
DSDAICPXUXPBCC-MWDJDSKUSA-N trimethyl-β-cyclodextrin Chemical compound COC[C@H]([C@H]([C@@H]([C@H]1OC)OC)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O3)[C@H](OC)[C@H]2OC)COC)O[C@@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@@H]3O[C@@H]1COC DSDAICPXUXPBCC-MWDJDSKUSA-N 0.000 claims description 4
238000002156 mixing Methods 0.000 claims description 3
238000000227 grinding Methods 0.000 claims description 2
230000000302 ischemic effect Effects 0.000 claims description 2
239000000463 material Substances 0.000 claims description 2
230000018052 penile erection Effects 0.000 claims description 2
230000008855 peristalsis Effects 0.000 claims description 2
230000029865 regulation of blood pressure Effects 0.000 claims description 2
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims 1
238000007911 parenteral administration Methods 0.000 claims 1
239000012429 reaction media Substances 0.000 claims 1
239000003513 alkali Substances 0.000 abstract description 2
238000003801 milling Methods 0.000 abstract 1
239000007790 solid phase Substances 0.000 description 13
238000004128 high performance liquid chromatography Methods 0.000 description 12
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 10
239000005695 Ammonium acetate Substances 0.000 description 10
229940043376 ammonium acetate Drugs 0.000 description 10
235000019257 ammonium acetate Nutrition 0.000 description 10
239000000126 substance Substances 0.000 description 10
239000012153 distilled water Substances 0.000 description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
239000001301 oxygen Substances 0.000 description 7
229910052760 oxygen Inorganic materials 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
XLFWDASMENKTKL-UHFFFAOYSA-N molsidomine Chemical compound O1C(N=C([O-])OCC)=C[N+](N2CCOCC2)=N1 XLFWDASMENKTKL-UHFFFAOYSA-N 0.000 description 6
ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 6
238000007664 blowing Methods 0.000 description 5
239000001307 helium Substances 0.000 description 5
229910052734 helium Inorganic materials 0.000 description 5
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 5
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
241000283973 Oryctolagus cuniculus Species 0.000 description 4
230000002776 aggregation Effects 0.000 description 4
238000004220 aggregation Methods 0.000 description 4
210000004185 liver Anatomy 0.000 description 4
229960004027 molsidomine Drugs 0.000 description 4
235000021317 phosphate Nutrition 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
238000002211 ultraviolet spectrum Methods 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
238000002835 absorbance Methods 0.000 description 3
235000010323 ascorbic acid Nutrition 0.000 description 3
238000010668 complexation reaction Methods 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
230000006870 function Effects 0.000 description 3
239000002840 nitric oxide donor Substances 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
SUVNDDIHQBSEAX-UHFFFAOYSA-N C(#N)C=C1N(CCOC1)N Chemical compound C(#N)C=C1N(CCOC1)N SUVNDDIHQBSEAX-UHFFFAOYSA-N 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
229940072107 ascorbate Drugs 0.000 description 2
239000011668 ascorbic acid Substances 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
150000001642 boronic acid derivatives Chemical class 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
210000001715 carotid artery Anatomy 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
230000000536 complexating effect Effects 0.000 description 2
230000008602 contraction Effects 0.000 description 2
238000001514 detection method Methods 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000008101 lactose Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
239000008055 phosphate buffer solution Substances 0.000 description 2
AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 2
150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
210000002381 plasma Anatomy 0.000 description 2
210000004623 platelet-rich plasma Anatomy 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
230000006641 stabilisation Effects 0.000 description 2
238000011105 stabilization Methods 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 2
150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
QGKBSGBYSPTPKJ-UZMKXNTCSA-N 2,6-di-o-methyl-β-cyclodextrin Chemical compound COC[C@H]([C@H]([C@@H]([C@H]1OC)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O3)[C@H](O)[C@H]2OC)COC)O[C@@H]1O[C@H]1[C@H](O)[C@@H](OC)[C@@H]3O[C@@H]1COC QGKBSGBYSPTPKJ-UZMKXNTCSA-N 0.000 description 1
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
102100032381 Alpha-hemoglobin-stabilizing protein Human genes 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
229920001353 Dextrin Chemical class 0.000 description 1
239000004375 Dextrin Chemical class 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
239000001116 FEMA 4028 Substances 0.000 description 1
108010078321 Guanylate Cyclase Proteins 0.000 description 1
102000014469 Guanylate cyclase Human genes 0.000 description 1
101000797984 Homo sapiens Alpha-hemoglobin-stabilizing protein Proteins 0.000 description 1
150000000994 L-ascorbates Chemical class 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
239000002253 acid Substances 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000008901 benefit Effects 0.000 description 1
WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
235000011175 beta-cyclodextrine Nutrition 0.000 description 1
229960004853 betadex Drugs 0.000 description 1
238000010170 biological method Methods 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
238000011088 calibration curve Methods 0.000 description 1
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000035602 clotting Effects 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000008139 complexing agent Substances 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
210000003038 endothelium Anatomy 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
150000004675 formic acid derivatives Chemical class 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
159000000011 group IA salts Chemical class 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
150000002484 inorganic compounds Chemical class 0.000 description 1
229910010272 inorganic material Inorganic materials 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
FKDHHVKWGRFRTG-UHFFFAOYSA-N linsidomine Chemical compound [N-]1OC(=N)C=[N+]1N1CCOCC1 FKDHHVKWGRFRTG-UHFFFAOYSA-N 0.000 description 1
230000003908 liver function Effects 0.000 description 1
230000007774 longterm Effects 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
KEAFBPBSUPYFGT-UHFFFAOYSA-N n-(cyanomethyl)-n-morpholin-4-ylnitrous amide Chemical compound N#CCN(N=O)N1CCOCC1 KEAFBPBSUPYFGT-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
239000002245 particle Substances 0.000 description 1
SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
229960001802 phenylephrine Drugs 0.000 description 1
238000006303 photolysis reaction Methods 0.000 description 1
230000015843 photosynthesis, light reaction Effects 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
150000004032 porphyrins Chemical class 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
229940063675 spermine Drugs 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000007704 transition Effects 0.000 description 1
238000002525 ultrasonication Methods 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1

Classifications

- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- 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
- A61K47/6949—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 inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
- C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nanotechnology (AREA)
Molecular Biology (AREA)
Epidemiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Medical Informatics (AREA)
Crystallography & Structural Chemistry (AREA)
Biochemistry (AREA)
Materials Engineering (AREA)
Polymers & Plastics (AREA)
Biophysics (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Medicinal Preparation (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Saccharide Compounds (AREA)
Detergent Compositions (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

HRP9401183A 1994-04-26 1995-04-25 Novel sin-1 cyclodextrin inclusion complexes HRP950249A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
HU9401183A HU218280B (en)	1994-04-26	1994-04-26	Cyclodextrin inclusion complexes containing sin-1a which are stable intheir solid state, process for their preparation and pharmaceutical compositions containing the comlexes

Publications (1)

Publication Number	Publication Date
HRP950249A2 true HRP950249A2 (en)	1997-10-31

Family

ID=10985114

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HRP9401183A HRP950249A2 (en)	1994-04-26	1995-04-25	Novel sin-1 cyclodextrin inclusion complexes

Country Status (32)

Country	Link
US (1)	US5698535A (lt)
EP (1)	EP0705255B1 (lt)
JP (1)	JP3434828B2 (lt)
KR (1)	KR960703404A (lt)
CN (1)	CN1060164C (lt)
AT (1)	ATE197708T1 (lt)
AU (1)	AU694219B2 (lt)
BG (1)	BG61974B1 (lt)
BR (1)	BR9506155A (lt)
CA (1)	CA2163539C (lt)
CZ (1)	CZ316395A3 (lt)
DE (1)	DE69519463T2 (lt)
DK (1)	DK0705255T3 (lt)
ES (1)	ES2153897T3 (lt)
FI (1)	FI956156A0 (lt)
GR (1)	GR3035356T3 (lt)
HR (1)	HRP950249A2 (lt)
HU (1)	HU218280B (lt)
IL (1)	IL113491A (lt)
LT (1)	LT4167B (lt)
LV (1)	LV11543B (lt)
MD (1)	MD1419G2 (lt)
NO (1)	NO311030B1 (lt)
NZ (1)	NZ285149A (lt)
PL (1)	PL312183A1 (lt)
PT (1)	PT705255E (lt)
RO (1)	RO114449B1 (lt)
RU (1)	RU2136698C1 (lt)
SI (1)	SI0705255T1 (lt)
SK (1)	SK155195A3 (lt)
WO (1)	WO1995029172A1 (lt)
YU (1)	YU25995A (lt)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6143746A (en) *	1994-01-21	2000-11-07	Icos Corporation	Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use
CA2391008C (en) *	1999-11-12	2009-12-22	Pitha & Pitha Llc	Crystalline mixtures of partial methyl ethers of beta-cyclodextrin and related compounds
FR2805462B1 (fr) *	2000-02-24	2003-08-15	Therabel Res	Nouvelle forme galenique orale a liberation prolongee de la molsidomine
TWI321054B (en) *	2000-12-19	2010-03-01	California Inst Of Techn	Compositions containing inclusion complexes
EP1219306A1 (en) *	2000-12-29	2002-07-03	Nicox S.A.	Compositions comprising cyclodextrins and NO- releasing drugs
ES2377318T3 (es)	2002-09-06	2012-03-26	Cerulean Pharma Inc.	Polímeros a base de ciclodextrina para el suministro de los agentes terapéuticos enlazados covalentemente a ellos
RU2332425C2 (ru) *	2002-09-06	2008-08-27	Инсёрт Терапьютикс, Инк.	Полимеры на основе циклодекстрина для доставки терапевтических средств
KR20050051686A (ko) *	2002-10-09	2005-06-01	인설트 테라페틱스, 인코퍼레이티드	사이클로덱스트린-기초한 재료, 조성물 및 이의 용도
US20080176958A1 (en)	2007-01-24	2008-07-24	Insert Therapeutics, Inc.	Cyclodextrin-based polymers for therapeutics delivery
CN102781237A (zh) *	2009-11-23	2012-11-14	天蓝制药公司	用于传递治疗剂的基于环糊精的聚合物
US20140094432A1 (en)	2012-10-02	2014-04-03	Cerulean Pharma Inc.	Methods and systems for polymer precipitation and generation of particles
JP7110360B2 (ja)	2017-10-09	2022-08-01	テルモビーシーティーバイオテクノロジーズ，エルエルシー	凍結乾燥方法
CN113597532B (zh)	2019-03-14	2023-02-17	泰尔茂比司特生物技术有限公司	冻干容器填充固定装置、系统及使用方法
CN116249522A (zh) *	2020-07-20	2023-06-09	深圳迈瑞生物医疗电子股份有限公司	一种组合物的血小板解聚用途、解聚试剂及解聚方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3780180A (en)	1971-02-04	1973-12-18	Sandoz Ag	N-substituted amino-n-nitroso-aminoace-tonitriles in the treatment of hypertension
US5039705A (en) *	1989-09-15	1991-08-13	The United States Of America As Represented By The Department Of Health And Human Services	Anti-hypertensive compositions of secondary amine-nitric oxide adducts and use thereof
US5208233A (en) *	1989-09-15	1993-05-04	The United States Of America As Represented By The Department Of Health And Human Services	Anti-hypertensive compositions of secondary amine-nitric oxide adducts and use thereof
US5212204A (en) *	1989-10-18	1993-05-18	The United States Of America As Represented By The Department Of Health And Human Services	Antihypertensive compositions and use thereof
HU212730B (en) *	1990-03-28	1996-10-28	Chinoin Gyogyszer Es Vegyeszet	Process for producing inclusion complexes of cyclodextrine or its derivative and 3-morpholino-sydnonimine or its salt or its tautomer and pharmaceutical compositions containing them
WO1993007114A1 (en) *	1991-09-24	1993-04-15	The United States Of America, Represented By The Secretary, Department Of Health And Human Services	Oxygen substituted derivatives of nucleophile-nitric oxide adducts as nitric oxide donor prodrugs
US5389675A (en) *	1992-03-27	1995-02-14	The United States Of America As Represented By The Department Of Health And Human Services	Mixed ligand metal complexes of nitric oxide-nucleophile adducts useful as cardiovascular agents

1994
- 1994-04-26 HU HU9401183A patent/HU218280B/hu not_active IP Right Cessation
1995
- 1995-04-25 BR BR9506155A patent/BR9506155A/pt not_active Application Discontinuation
- 1995-04-25 DK DK95918104T patent/DK0705255T3/da active
- 1995-04-25 AT AT95918104T patent/ATE197708T1/de active
- 1995-04-25 HR HRP9401183A patent/HRP950249A2/hr not_active Application Discontinuation
- 1995-04-25 CZ CZ953163A patent/CZ316395A3/cs unknown
- 1995-04-25 JP JP52720795A patent/JP3434828B2/ja not_active Expired - Lifetime
- 1995-04-25 CA CA002163539A patent/CA2163539C/en not_active Expired - Lifetime
- 1995-04-25 ES ES95918104T patent/ES2153897T3/es not_active Expired - Lifetime
- 1995-04-25 CN CN95190353A patent/CN1060164C/zh not_active Expired - Fee Related
- 1995-04-25 NZ NZ285149A patent/NZ285149A/en unknown
- 1995-04-25 MD MD95-0440A patent/MD1419G2/ro unknown
- 1995-04-25 RU RU96100760A patent/RU2136698C1/ru active
- 1995-04-25 PT PT95918104T patent/PT705255E/pt unknown
- 1995-04-25 PL PL95312183A patent/PL312183A1/xx unknown
- 1995-04-25 SI SI9530435T patent/SI0705255T1/xx unknown
- 1995-04-25 AU AU24159/95A patent/AU694219B2/en not_active Expired
- 1995-04-25 IL IL11349195A patent/IL113491A/en not_active IP Right Cessation
- 1995-04-25 RO RO95-02248A patent/RO114449B1/ro unknown
- 1995-04-25 YU YU25995A patent/YU25995A/sh unknown
- 1995-04-25 SK SK1551-95A patent/SK155195A3/sk unknown
- 1995-04-25 DE DE69519463T patent/DE69519463T2/de not_active Expired - Lifetime
- 1995-04-25 WO PCT/HU1995/000011 patent/WO1995029172A1/en not_active Ceased
- 1995-04-25 KR KR1019950705912A patent/KR960703404A/ko not_active Ceased
- 1995-04-25 EP EP95918104A patent/EP0705255B1/en not_active Expired - Lifetime
- 1995-04-25 US US08/571,853 patent/US5698535A/en not_active Expired - Fee Related
- 1995-12-20 FI FI956156A patent/FI956156A0/fi not_active Application Discontinuation
- 1995-12-22 LT LT95-133A patent/LT4167B/lt not_active IP Right Cessation
- 1995-12-22 LV LVP-95-383A patent/LV11543B/en unknown
- 1995-12-22 NO NO19955283A patent/NO311030B1/no not_active IP Right Cessation
1996
- 1996-01-26 BG BG100313A patent/BG61974B1/bg unknown
2001
- 2001-02-02 GR GR20010400181T patent/GR3035356T3/el unknown

Also Published As

Publication number	Publication date
NO311030B1 (no)	2001-10-01
MD1419G2 (ro)	2000-11-30
JP3434828B2 (ja)	2003-08-11
HU218280B (en)	2000-07-28
HUT70750A (en)	1995-10-30
BG100313A (bg)	1996-07-31
WO1995029172A1 (en)	1995-11-02
MD1419F2 (en)	2000-02-29
DK0705255T3 (da)	2000-12-11
SI0705255T1 (en)	2001-04-30
CA2163539A1 (en)	1995-11-02
CZ316395A3 (en)	1996-05-15
IL113491A (en)	2002-03-10
CN1060164C (zh)	2001-01-03
KR960703404A (ko)	1996-08-17
NO955283D0 (no)	1995-12-22
MD950440A (ro)	1997-10-31
DE69519463T2 (de)	2001-06-28
ATE197708T1 (de)	2000-12-15
RU2136698C1 (ru)	1999-09-10
GR3035356T3 (en)	2001-05-31
US5698535A (en)	1997-12-16
LV11543B (en)	1996-12-20
LT4167B (en)	1997-06-25
IL113491A0 (en)	1995-07-31
BR9506155A (pt)	1996-04-16
EP0705255A1 (en)	1996-04-10
PL312183A1 (en)	1996-04-01
JPH09503546A (ja)	1997-04-08
HU9401183D0 (en)	1994-07-28
FI956156A7 (fi)	1995-12-20
DE69519463D1 (de)	2000-12-28
CA2163539C (en)	2003-04-01
NO955283L (no)	1995-12-22
CN1128028A (zh)	1996-07-31
LV11543A (lv)	1996-10-20
RO114449B1 (ro)	1999-04-30
BG61974B1 (bg)	1998-11-30
NZ285149A (en)	1998-06-26
FI956156A0 (fi)	1995-12-20
YU25995A (sh)	1998-08-14
PT705255E (pt)	2001-05-31
EP0705255B1 (en)	2000-11-22
ES2153897T3 (es)	2001-03-16
AU694219B2 (en)	1998-07-16
LT95133A (en)	1996-10-25
AU2415995A (en)	1995-11-16
SK155195A3 (en)	1997-05-07

Legal Events

Date	Code	Title
1997-10-09	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
1997-10-31	A1OB	Publication of a patent application
2001-09-02	ODBC	Application rejected

Publication	Publication Date	Title
HRP950249A2 (en)	1997-10-31	Novel sin-1 cyclodextrin inclusion complexes
JPH08506119A (ja)	1996-07-02	認識活性化剤ＣＩ−９７９ＨＣ▲ｌ▼の中性安定化複合体
EP0477315B1 (en)	1996-05-29	Inclusion complexes of n-ethoxycarbonyl-3-morpholino-sydnonimine or salts formed with cyclodextrin derivatives, preparation thereof and pharmaceutical compositions containing the same
EP0478732B1 (en)	1998-09-09	Inclusion complexes of 3-morpholino-sydnonimine or its salts or its tautomer isomer, process for the preparation thereof, and pharmaceutical compositions containing the same
SI20974A (sl)	2003-02-28	Alkoksi substituirane benzimidazolne spojine, farmacevtski pripravki, ki jih vsebujejo ter metode za njihovo uporabo
KIKUCHI et al.	1987	Improvement of chemical instability of carmoful in β-cyclodextrin solid complex by utilizing some organic acids
RU2389491C2 (ru)	2010-05-20	Комплекс, содержащий меквитазин (mequitazine), циклодекстрин и агент взаимодействия
Ma	1998	Evaluation of sulfobutyl ether beta-cyclodextrin as a solubilizing/stabilizing and freeze-drying excipient
Mel’nikova et al.	2008	Structure of surface films of malonate mono-and dinitroxyl methanofullerenes
KR20050105005A (ko)	2005-11-03	란소프라졸을 유효성분으로 함유하는 주사제 조성물
JPH0516837B2 (lt)	1993-03-05
SK278809B6 (sk)	1998-03-04	Inklúzny komplex 3-morfolinosydnonimínu alebo jeho