LV12859B - Farmaceitiskas kompozīcijas ar morfīnu intranazālai ievadīšanai un to iegūšanas paņēmieni - Google Patents
Farmaceitiskas kompozīcijas ar morfīnu intranazālai ievadīšanai un to iegūšanas paņēmieni Download PDFInfo
- Publication number
- LV12859B LV12859B LVP-01-169A LV010169A LV12859B LV 12859 B LV12859 B LV 12859B LV 010169 A LV010169 A LV 010169A LV 12859 B LV12859 B LV 12859B
- Authority
- LV
- Latvia
- Prior art keywords
- morphine
- acceptable salt
- pharmaceutically acceptable
- absorption
- pharmaceutical composition
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 35
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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Claims (29)
- LV 12859 IZGUDROJUMA FORMULA 1. Farmaceitiska kompozīcija intranazāla ievadīšanai, kurā ietilpst morfīns vai tā farmaceitiski pieņemams sāls ar pH no 3,0 līdz 7,0.
- 2. Farmaceitiska kompozīcija saskaņā ar l.punktu, kurā ietilpst morfina vai tā farmaceitiski pieņemama sāls terapeitiski efektīvs daudzums, lai izsauktu zīdītāju sāpju remdināšanas vai anestēzijas reakciju.
- 3. Farmaceitiska kompozīcija saskaņā ar l.punktu, kurā papildus ietilpst morfins vai tā farmaceitiski pieņemams sāls kopā ar nazāla ievadīšanas (padeves) sistēmu.
- 4. Farmaceitiska kompozīcija saskaņā ar 3.punktu, kas atšķiras ar to, ka morfins vai tā farmaceitiski pieņemams sāls disperģēts ūdens vai neūdens kompozīcijā.
- 5. Farmaceitiska kompozīcija saskaņā ar 4.punktu, kas a t š ķ i r a s ar to, ka morfina vai tā farmaceitiski pieņemama sāls koncentrācija ir zemāka par 50 % mas./mas.
- 6. Farmaceitiska kompozīcija saskaņā ar 4.punktu, kas a t š ķ i r a s ar to, ka morfina vai tā farmaceitiski pieņemama sāls koncentrācija ir zemāka par 10 % mas./mas.
- 7. Farmaceitiska kompozīcija saskaņā ar 4.punktu, kas a t š ķ i r a s ar to, ka morfins vai tā farmaceitiski pieņemams sāls disperģēts suspensijā, šķīdumos, pulveros, gelos, ziedēs un krēmos.
- 8. Farmaceitiska kompozīcija saskaņā ar 3.punktu, kas a t š ķ i r a s ar to, ka nazāla ievadīšanas (padeves) sistēmā ietilpst buferšķīdums morfina vai tā farmaceitiski pieņemama sāls pH uzturēšanai, biezinātājs, mitrinātājs, absorbcijas palielinātājs un šo komponentu kombinācijas.
- 9. Farmaceitiska kompozīcija saskaņā ar 8.punktu, kurā papildus ietilpst viena vai vairākas farmaceitiskas palīgvielas. 2
- 10. Farmaceitiska kompozīcija saskaņā ar 8.punktu, kurā papildus ietilpst dispersijas (suspensijas) stabilizators.
- 11. Farmaceitiska kompozīcija saskaņā ar 8.punktu, kas a t š ķ i r a s ar to, ka buferšķīdumu izvēlas no grupas, kas sastāv no acetāta, citrāta, prolamīna, karbonāta, fosfāta un šo buferšķīdumu kombinācijām.
- 12. Farmaceitiska kompozīcija saskaņā ar 8.punktu, kas a t š ķ i r a s ar to, ka biezinātāju izvēlas no grupas, kas sastāv no metilcelulozes, ksantāna sveķiem, karboksimetilcelulozes, hidroksipropilcelulozes, karbomēra, polivinilspirta, alginātiem, gumiarābika, hitozāna un šo biezinātāju kombinācijām.
- 13. Farmaceitiska kompozīcija saskaņā ar 8.punktu, kas a t š ķ i r a s ar to, ka mitrinātāju izvēlas no grupas, kas sastāv no sorbīta, glicerīna, minerāleļļas, augu eļļas un šo mitrinātāju kombinācijām.
- 14. Farmaceitiska kompozīcija saskaņā ar 8.punktu, kas a t š ķ i r a s ar to, ka absorbcijas palielinātāju izvēlas no grupas, kas sastāv no nātrija laurilsulfata, nātrija salicilāta, oleīnskābes, lecitīna, dehidratēta spirta, Tween, Span, polioksila 40 stearāta, polioksietilēna 50 stearāta, dinātrija edetāta, propilēnglikola, glicerolmonooleāta, fuziātiem, žulta sāļiem, oktoksinola un šo absorbcijas palielinātāju kombinācijām.
- 15. Farmaceitiska kompozīcija saskaņā ar 8.punktu, kas a t š ķ i r a s ar to, ka absorbcijas palielinātāju izvēlas no grupas, kas sastāv no anjonu, katjonu un nekatjonu absorbcijas palielinātājiem un to kombinācijām.
- 16. Paņēmiens zīdītāju sāpju remdināšanas vai anestēzijas reakcijas izsaukšanai, kurā ietilpst morfīna un tā farmaceitiski pieņemama sāls ar pH no 3,0 līdz 7,0 terapeitiski efektīva daudzuma ievadīšana nazāli.
- 17. Paņēmiens zīdītāju sāpju remdināšanas vai anestēzijas reakcijas izsaukšanai, kurā ietilpst morfīna un tā farmaceitiski pieņemama sāls ar pH no 3,0 līdz 7,0 terapeitiski efektīva daudzuma ievadīšana zīdītājiem kopā ar nazāla ievadīšanas (padeves) sistēmu. 3 LV 12859
- 18. Paņēmiens saskaņā ar 17.punktu, kas atšķiras ar to, ka morfīns vai ta farmaceitiski pieņemams sāls disperģēts ūdens vai neūdens kompozīcijā.
- 19. Paņēmiens saskaņā ar 18.punktu, kas a t š ķ i r a s ar to, ka morftna vai tā farmaceitiski pieņemama sāls koncentrācija ir zemāka par 50 % mas./mas.
- 20. Paņēmiens saskaņā ar 18.punktu, kas a t š ķ i r a s ar to, ka morftna vai tā farmaceitiski pieņemama sāls koncentrācija ir zemāka par 10 % mas./mas.
- 21. Paņēmiens saskaņā ar 18.punktu, kas a t š ķ i r a s ar to, ka morfīns vai tā farmaceitiski pieņemams sāls disperģēts suspensijā, šķīdumos, pulveros, gelos, ziedēs un krēmos.
- 22. Paņēmiens saskaņā ar 17.punktu, kas a t š ķ i r a s ar to, ka nazāla ievadīšanas (padeves) sistēmā ietilpst buferšķīdums morfīna vai tā farmaceitiski pieņemama sāls pH uzturēšanai, biezinātājs, mitrinātājs, absorbcijas palielinātājs un šo komponentu kombinācijas.
- 23. Paņēmiens saskaņā ar 22.punktu, kurā papildus ietilpst viena vai vairākas farmaceitiskas palīgvielas.
- 24. Paņēmiens saskaņā ar 22.punktu, kurā papildus ietilpst dispersijas (suspensijas) stabilizators.
- 25. Paņēmiens saskaņā ar 22.punktu, kas a t š ķ i r a s ar to, ka buferšķīdumu izvēlas no grupas, kas sastāv no acetāta, citrāta, prolamīna, karbonāta, fosfāta un šo buferšķīdumu kombinācijām.
- 26. Paņēmiens saskaņā ar 22.punktu, kas a t š ķ i r a s ar to, ka biezinātāju izvēlas no grupas, kas sastāv no metilcelulozes, ksantāna sveķiem, karboksimetilcelulozes, hidroksipropilcelulozes, karbomēra, polivinilspirta, alginātiem, gumiarābika, hitozāna un šo biezinātāju kombinācijām.
- 27. Paņēmiens saskaņā ar 22.punktu, kas a t š ķ i r a s ar to, ka mitrinātāju izvēlas no grupas, kas sastāv no sorbīta, glicerīna, minerāleļļas, augu eļļas un šo mitrinātāju kombinācijām. 4
- 28. Paņēmiens saskaņā ar 22.punktu, kas a t š ķ i r a s ar to, ka absorbcijas palielinātāju izvēlas no grupas, kas sastāv no nātrija laurilsulfata, nātrija salicilāta, oleīnskābes, lecitīna, dehidratēta spirta, Tween, Span, polioksila 40 stearāta, polioksietilēna 50 stearāta, dinātrija edetāta, propilēnglikola, glicerolmonooleāta, fuziātiem, žulta sāļiem, oktoksinola un šo absorbcijas palielinātāju kombinācijām.
- 29. Paņēmiens saskaņā ar 22.punktu, kas a t š ķ i r a s ar to, ka absorbcijas palielinātāju izvēlas no grupas, kas sastāv no anjonu, katjonu un nekatjonu absorbcijas palielinātājiem un to kombinācijām.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US33453799A | 1999-06-16 | 1999-06-16 |
Publications (1)
Publication Number | Publication Date |
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LV12859B true LV12859B (lv) | 2002-12-20 |
Family
ID=23307687
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LVP-01-169A LV12859B (lv) | 1999-06-16 | 2002-01-18 | Farmaceitiskas kompozīcijas ar morfīnu intranazālai ievadīšanai un to iegūšanas paņēmieni |
Country Status (30)
Country | Link |
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US (1) | US6677346B1 (lv) |
EP (2) | EP1183027A4 (lv) |
JP (1) | JP2003501467A (lv) |
KR (1) | KR20020016831A (lv) |
AU (1) | AU774175B2 (lv) |
BG (1) | BG106221A (lv) |
BR (1) | BR0012082A (lv) |
CA (1) | CA2374877C (lv) |
CZ (1) | CZ20014399A3 (lv) |
DE (1) | DE10084709T1 (lv) |
DK (1) | DK200101859A (lv) |
EE (1) | EE200100677A (lv) |
ES (1) | ES2197792B1 (lv) |
FI (1) | FI20012462A (lv) |
GB (1) | GB2367005A (lv) |
HR (1) | HRP20010926A2 (lv) |
HU (1) | HUP0201856A3 (lv) |
IS (1) | IS6202A (lv) |
LT (1) | LT4976B (lv) |
LU (1) | LU90859B1 (lv) |
LV (1) | LV12859B (lv) |
MX (1) | MXPA01012879A (lv) |
NO (1) | NO20015931L (lv) |
NZ (1) | NZ515783A (lv) |
PL (1) | PL352556A1 (lv) |
SE (1) | SE0104203L (lv) |
SI (1) | SI20850A (lv) |
SK (1) | SK18172001A3 (lv) |
TR (1) | TR200103613T2 (lv) |
WO (1) | WO2000076506A1 (lv) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9924797D0 (en) | 1999-10-20 | 1999-12-22 | West Pharm Serv Drug Res Ltd | Compound |
US20060083691A1 (en) * | 2000-05-10 | 2006-04-20 | Wermeling Daniel P | Intranasal opioid compositions, delivery devices and methods of using same |
US20040115133A1 (en) * | 2000-05-10 | 2004-06-17 | Wermeling Daniel P. | Intranasal opioid compositions |
WO2002024116A1 (en) * | 2000-09-20 | 2002-03-28 | Shahinian, Lee, Jr. | Self-preserved nasal, inhalable, and topical ophthalmic preparations and medications |
US20030003113A1 (en) * | 2001-06-29 | 2003-01-02 | Lewandowski Leon J. | Individualized addiction cessation therapy |
GB0210264D0 (en) * | 2002-05-03 | 2002-06-12 | Arakis Ltd | The treatment of pain and migraine headache |
US20040102476A1 (en) * | 2002-11-25 | 2004-05-27 | Chan Tai Wah | High concentration formulations of opioids and opioid derivatives |
US20050175679A1 (en) * | 2004-02-10 | 2005-08-11 | Michael Moshman | Controlled release formulations |
US9895444B2 (en) | 2004-08-25 | 2018-02-20 | Aegis Therapeutics, Llc | Compositions for drug administration |
US20140162965A1 (en) | 2004-08-25 | 2014-06-12 | Aegis Therapeutics, Inc. | Compositions for oral drug administration |
NZ555501A (en) | 2004-11-24 | 2010-01-29 | Medpointe Healthcare Inc | Compositions comprising azelastine and methods of use thereof |
US9415034B2 (en) * | 2005-01-05 | 2016-08-16 | National Defense Medical Center | Inhibitors and enhancers of uridine diphosphate-glucuronosyltransferase 2B (UGT2B) |
ES2277743B2 (es) * | 2005-06-02 | 2008-12-16 | Universidade De Santiago De Compostela | Nanoparticulas que comprenden quitosano y ciclodextrina. |
JP5276982B2 (ja) | 2005-08-26 | 2013-08-28 | ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティ | オキシトシンの投与による頭痛の処置のための方法 |
US20070212307A1 (en) * | 2006-02-10 | 2007-09-13 | Daniel Wermeling | Pharmaceutical Compositions Comprising an Opioid Receptor Antagonist and Methods of Using Same |
US8226949B2 (en) | 2006-06-23 | 2012-07-24 | Aegis Therapeutics Llc | Stabilizing alkylglycoside compositions and methods thereof |
BRPI0720434A2 (pt) * | 2006-12-22 | 2014-01-07 | Sigma Tau Ind Farmaceuti | Gel útil para liberação de fármacos oftálmicos |
GB2477545B (en) * | 2010-02-05 | 2011-12-21 | Special Products Ltd | A liquid morphine composition for buccal administration |
MX354249B (es) | 2011-05-13 | 2018-02-20 | Euro Celtique Sa | Formas de dosificación farmacéuticas intranasales que comprenden naloxona. |
EP2877178A1 (en) | 2012-07-26 | 2015-06-03 | Wockhardt Limited | Pharmaceutical composition comprising diamorphine for intranasal administration |
EP3082817A4 (en) * | 2013-12-18 | 2017-06-21 | Aegis Therapeutics, LLC | Compositions for drug administration |
US11135155B2 (en) | 2014-07-08 | 2021-10-05 | Hikma Pharmaceuticals Usa Inc. | Liquid naloxone spray |
EP3242676B1 (en) | 2015-01-07 | 2023-10-04 | Tonix Pharmaceuticals Holding Corp. | Magnesium-containing oxytocin formulations and methods of use |
CA3041308A1 (en) * | 2016-10-21 | 2018-04-26 | Somniferum Labs LLC | Method, system and apparatus for controlled delivery of opioid and other medications |
WO2019076997A1 (en) * | 2017-10-20 | 2019-04-25 | Chiesi Farmaceutici S.P.A. | PHARMACEUTICAL FORMULATIONS COMPRISING AN OPIOID RECEPTOR AGONIST AS ACTIVE SUBSTANCES, METHODS OF MAKING THEM AND THERAPEUTIC USES THEREOF |
EA202091615A1 (ru) | 2018-12-21 | 2021-03-05 | Аегис Терапьютикс, Ллс | Интраназальные составы на основе эпинефрина и способы лечения заболевания |
CN115804754A (zh) * | 2022-12-16 | 2023-03-17 | 广州新济药业科技有限公司 | 吗啡鼻喷剂及其制备方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4464378A (en) * | 1981-04-28 | 1984-08-07 | University Of Kentucky Research Foundation | Method of administering narcotic antagonists and analgesics and novel dosage forms containing same |
US4464376A (en) | 1982-07-22 | 1984-08-07 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising caffeine and methods of using same |
GB8514665D0 (en) * | 1985-06-11 | 1985-07-10 | Eroceltique Sa | Oral pharmaceutical composition |
US5202128A (en) | 1989-01-06 | 1993-04-13 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
GB9202464D0 (en) * | 1992-02-05 | 1992-03-18 | Danbiosyst Uk | Composition for nasal administration |
EP0689438B1 (en) * | 1993-03-26 | 2003-06-04 | Franciscus Wilhelmus Henricus Maria Merkus | Pharmaceutical compositions for intranasal administration of apomorphine |
GB9426102D0 (en) | 1994-12-23 | 1995-02-22 | Merck Sharp & Dohme | Pharmacuetical compositions |
JP2001501212A (ja) * | 1996-09-27 | 2001-01-30 | ナステック ファーマシューティカル カンパニー インク | 睡眠促進用鼻腔内調製物及び同物を用いる方法 |
-
2000
- 2000-05-23 EP EP00936212A patent/EP1183027A4/en not_active Withdrawn
- 2000-05-23 EP EP04001252A patent/EP1419774A1/en not_active Withdrawn
- 2000-05-23 WO PCT/US2000/014157 patent/WO2000076506A1/en not_active Application Discontinuation
- 2000-05-23 JP JP2001502839A patent/JP2003501467A/ja active Pending
- 2000-05-23 ES ES200150086A patent/ES2197792B1/es not_active Expired - Lifetime
- 2000-05-23 SK SK1817-2001A patent/SK18172001A3/sk unknown
- 2000-05-23 AU AU51561/00A patent/AU774175B2/en not_active Ceased
- 2000-05-23 GB GB0128383A patent/GB2367005A/en not_active Withdrawn
- 2000-05-23 HU HU0201856A patent/HUP0201856A3/hu unknown
- 2000-05-23 NZ NZ515783A patent/NZ515783A/en unknown
- 2000-05-23 EE EEP200100677A patent/EE200100677A/xx unknown
- 2000-05-23 SI SI200020030A patent/SI20850A/sl not_active IP Right Cessation
- 2000-05-23 DE DE10084709T patent/DE10084709T1/de not_active Ceased
- 2000-05-23 KR KR1020017016009A patent/KR20020016831A/ko not_active Application Discontinuation
- 2000-05-23 CA CA002374877A patent/CA2374877C/en not_active Expired - Fee Related
- 2000-05-23 CZ CZ20014399A patent/CZ20014399A3/cs unknown
- 2000-05-23 BR BR0012082-0A patent/BR0012082A/pt not_active IP Right Cessation
- 2000-05-23 MX MXPA01012879A patent/MXPA01012879A/es unknown
- 2000-05-23 TR TR2001/03613T patent/TR200103613T2/xx unknown
- 2000-05-23 PL PL00352556A patent/PL352556A1/xx not_active Application Discontinuation
- 2000-06-15 US US09/594,916 patent/US6677346B1/en not_active Expired - Fee Related
-
2001
- 2001-12-04 NO NO20015931A patent/NO20015931L/no not_active Application Discontinuation
- 2001-12-12 DK DK200101859A patent/DK200101859A/da not_active Application Discontinuation
- 2001-12-13 LT LT2001119A patent/LT4976B/lt not_active IP Right Cessation
- 2001-12-13 HR HR20010926A patent/HRP20010926A2/hr not_active Application Discontinuation
- 2001-12-13 FI FI20012462A patent/FI20012462A/fi not_active IP Right Cessation
- 2001-12-13 LU LU90859A patent/LU90859B1/en active
- 2001-12-14 BG BG106221A patent/BG106221A/xx unknown
- 2001-12-14 IS IS6202A patent/IS6202A/is unknown
- 2001-12-14 SE SE0104203A patent/SE0104203L/ not_active Application Discontinuation
-
2002
- 2002-01-18 LV LVP-01-169A patent/LV12859B/lv unknown
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