TW200423969A - Controlled dosage aerosols with lecithin as surface-active agent - Google Patents
Controlled dosage aerosols with lecithin as surface-active agent Download PDFInfo
- Publication number
- TW200423969A TW200423969A TW092135946A TW92135946A TW200423969A TW 200423969 A TW200423969 A TW 200423969A TW 092135946 A TW092135946 A TW 092135946A TW 92135946 A TW92135946 A TW 92135946A TW 200423969 A TW200423969 A TW 200423969A
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- Prior art keywords
- controlled
- aerosol
- lecithin
- patent application
- glucocorticoid
- Prior art date
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- 239000000443 aerosol Substances 0.000 title claims abstract description 23
- 239000000787 lecithin Substances 0.000 title claims abstract description 11
- 235000010445 lecithin Nutrition 0.000 title claims abstract description 11
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 title claims abstract description 10
- 229940067606 lecithin Drugs 0.000 title claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 title claims abstract description 7
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000001282 iso-butane Substances 0.000 claims abstract description 13
- 239000003380 propellant Substances 0.000 claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims description 10
- 239000003862 glucocorticoid Substances 0.000 claims description 9
- 235000010469 Glycine max Nutrition 0.000 claims description 6
- 239000000924 antiasthmatic agent Substances 0.000 claims description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 4
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 3
- 230000001088 anti-asthma Effects 0.000 claims description 3
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 claims description 3
- 229940092705 beclomethasone Drugs 0.000 claims description 3
- 150000003904 phospholipids Chemical class 0.000 claims description 3
- 229940083466 soybean lecithin Drugs 0.000 claims description 3
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims description 2
- 244000068988 Glycine max Species 0.000 claims description 2
- 229960004436 budesonide Drugs 0.000 claims description 2
- 229960000890 hydrocortisone Drugs 0.000 claims description 2
- 150000002632 lipids Chemical class 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims 3
- 229960002714 fluticasone Drugs 0.000 claims 2
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 claims 2
- 241000196324 Embryophyta Species 0.000 claims 1
- MKPDWECBUAZOHP-AFYJWTTESA-N Paramethasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O MKPDWECBUAZOHP-AFYJWTTESA-N 0.000 claims 1
- 229960002537 betamethasone Drugs 0.000 claims 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims 1
- 229960003957 dexamethasone Drugs 0.000 claims 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims 1
- 229960000676 flunisolide Drugs 0.000 claims 1
- 229960002858 paramethasone Drugs 0.000 claims 1
- 229960005205 prednisolone Drugs 0.000 claims 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims 1
- 229960004618 prednisone Drugs 0.000 claims 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 description 7
- 235000013601 eggs Nutrition 0.000 description 7
- 238000009472 formulation Methods 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 3
- 238000004062 sedimentation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000008347 soybean phospholipid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- XYZZKVRWGOWVGO-UHFFFAOYSA-N Glycerol-phosphate Chemical compound OP(O)(O)=O.OCC(O)CO XYZZKVRWGOWVGO-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 230000001813 broncholytic effect Effects 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- -1 fatty acid esters Chemical class 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000008246 gaseous mixture Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000007971 pharmaceutical suspension Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 229940064707 sympathomimetics Drugs 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P37/08—Antiallergic agents
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
200423969 五、發明說明（1) 【發明所屬之技術領域】 本發明之標的為劑量經控制之氣溶膠，包含至少一種 藥劑’以及經壓力液化作為推進劑之異丁烷與作為表面活 性劑之卵磷脂所製得之混合物。 本發明更特定是關於劑量經控制之氣溶膠，包含至少 種來自酶皮質素（glucocorticoid)群組具有抗氣喘行為 之藥劑’以及經壓力液化作為推進劑之異丁烷與卵磷脂所 製传之混合物。 L先前 氣 稱為量 體來作 由壓力 之閥結 形式之 藥劑， 合物理 技術】 溶膠加壓氣 化氣溶膠， 為推進劑， 谷器、較佳 構，與通常 經加壓液化 所組成。經 想地應該與 一單一液相。要不 該形成一懸浮態， 成氣相。依其含有 是醫藥界，或作為 劑量經控制之 罐組， 其所製 早為已 為金屬 由活性 的推進 加壓液 活性物 然，經 其活性 之藥劑 室内噴 氣溶膠 或稱為劑量經控制之氣溶膠， 得並使用加壓液化氣體或壓縮 知。一般說來，此等量化氣溶 或玻璃者，具有用以抽回其内 物質溶液以及氣狀或氣體混合 劑所組成之，實際有效要噴出 化的氣體或經加壓液化的氣體 質以任何的比例互溶，使得形 加壓液化的氣體或氣體混合物 物質要能夠容易搖散而在其上 ’此等量化氣溶膠用於化妝品 霧劑’驅蟲噴劑，或類似者。 的推進劑必須要滿足一些特定
第5頁
200423969 五、發明說明（2) 要求。其無論如何都不能與活性藥劑溶液的組份反應。還 有，推進劑既不能有刺激性也不能有毒性。已證明氟氯碳 化物特別適用。然而，由於其臭氧耗竭效應，需要發展其 他的推進劑。然而，這些取代品的品質必須要能與氟氣碳 化物相抗衡；最重要的是，其既不能對健康造成危害亦要 具有環境相容性。開始，部分鹵化之氟氯碳化物常用作替 代品，但是仍有高度不可接受之臭氧耗竭性。 DE 4 1 32 1 76揭示劑量經控制之氣溶膠，用於 isoprenal in衍生物，所謂之冷擬交感神經作用劑 (sympathomimetics)，或是非固醇類抗發炎藥劑DNCGi 投藥，其中異丁烷作為推進劑。 DE 1 99 1 1 064揭示劑量經控制之氣溶膠，含有 broncholytic及/或來自醣皮質素類群組之抗發炎藥劑， 以異丁烷作為推進劑，而以油酸或Span 85作為表面活性 物質。此等劑量氣溶膠，然而，有著不良再懸浮性的缺 點，與活性物質在推進劑中太快的沉降性。
L發明内容J 本發明之目的在於楹徂 ^ A 、、徒供一種用於樂劑之劑量經控 氣溶膠，特別是來自酶戌暂丰 反貝素群組用於抗氣喘之藥劑 沒有DE 1 99 1 1 0 64之你批也丨〆 、、二控制氣溶膠已知之缺點。
第6頁 200423969 五、發明說明（3) 很驚訝的發現’佐劑卵磷脂會造成藥劑在再懸浮性上 明顯的進步’特別疋在異丁烧中之_皮質素。 【實施方式】 卵石粦脂為磷酸甘/由月旨（glyCer〇phosphol ipid )類， 其由脂肪酸類、甘油、磷酸與膽鹼所組成。天然存在的卵 磷脂類為1，2-二醯-sn〜甘油—3__磷酸之衍生物。當從生物 中萃取出卵碟脂時，總是會得到卵磷脂之混合物，其 τ之脂肪酸酯各有不同。 筚界f據本發明’較佳之卵磷脂為大豆卵磷脂，其已在醫 樂界中廣用作為乳化劑。 與力口了大豆卵填腊点 多種表‘ ；次吊用於製造抗氣喘量化氣溶膠之 / 4里衣面活性劑，在里 較時，1、，办由，"丁燒中藥劑之懸浮物沉降行為作比 以親察到，亦W ^ t 脂之藥澈丨縣、-仏hj從下列之實例看出’有大豆卵磷 了 1 0 ^ Θ 、'儿降時間要比有油酸之藥劑懸浮物者長 。’比有Span 85之藥劑懸浮物者長了 5倍。 在更進一步的測讀、由 1:21 n ’藥劑對大豆卵填脂之比例為 ^ ^ # t #1 „ Λ ^ ^ ^ "I m ^ ? ^ 且_磷脂之比例為1 : 0 · 5。 實例
第7頁 200423969 五、發明說明（4) 藥劑懸浮物在異丁烷中，使用不同的表面活性藥劑，懸浮 行為的比較 相對沉降時間 醣 皮 質 素 油 酸 ( 100 ： 1 ) 1 醣 皮 質 素 Sp an 85(1 :1 : ) 2 St 皮 質 素 大 豆 卵 填脂 (1 ： 2 ) 10 醣 皮 質 素 大 豆 卵 磷脂 (1： 1 ) 10 醣 皮 質 素 大 豆 卵 磷脂 (1 ： 0.5) 10 在 更進一 步 的 測試 中， 下列之調配物 f特別有利 調配物1 醣皮質素 0. 1 % -0· 2 % 卵磷脂 0. 05 % -0. 4 % 異丁烷 99. 85 % -99. 4 % 調配物2 醣皮質素 卵磷脂 異丁烧 0.5% -1.0% 0· 25 % -4. 0 % 99. 75 % -95. 0 % 調配物3 0.1% -2.5% 0.05% -5.0% 99. 85 % -92. 5 % 倍氯美松（Beclomethasone) 大豆卵填脂 異丁烷
200423969 五、發明說明（5) 調配物4 可滅喘（Budesonide) 0· 1 % 0. 05% 〜5 99· 85%， 大豆卵磷脂 異丁烷 所有量均為重量百分比 本發明氣溶膠可藉由在推進劑與 而活性劑為固體之條件下混合多種二伤;而;$劑為液體， ^藥劑懸浮物經由閥在壓力下填入密閉的 罐^充填開始時為室溫。懸浮物的溫度大約為罐，洋鐵 1 〇 C。然後，將洋鐵罐充滿推進劑，並同二1 〇至+ 閥。 併清潔了 根據本發明之經控制之氣溶膠可用於治 物二特別是治療呼吸道之過敏性疾病，如氣二人颉或是動 鼻炎（乾草熱），較佳由口腔或是鼻腔吸入7或過敏性
第9頁 200423969 圖式簡單說明 無
llli· 第10頁
Claims (1)
- 200423969 六、申請專利範圍 ---— 1 · 一種劑量經控制之氣溶膠，含有至少一種藥劑、經壓 力液化之異丁烷作為·推進劑，與作為表面活性劑之一 脂。 2·如申j青專利範圍第丨項之劑量經控制之氣溶膠，其特徵 在於a亥藥劑為一醣皮質素，該醣皮質素較佳選自由皮質醇 (cortisol)、腎上腺皮脂酮（prednisone)、副腎皮質 素（prednisolone )、曱基副腎皮質素、曲安奈德 (triamcinolone) - predny1idene、f1uocortο 1 one、 paramethasone、右米塔松(dexame thasone )、美他貝松 (betamethasone)、flunisolide、氟替卡松 (fluticasone)、倍氣美松（beclomethasone)、可滅喘 (b u d e s ο n i d e )、及/或其抗氣喘活性衍生物及/或其混合 物所組成之群組。 3 ·如申請專利範園第1或2項之劑量經控制之氣溶膠’其特 徵為，對應之調配成份為·· 醣皮質素 0·1%-〇·2% 卵碟脂 0.05% -0.4% 显丁 ρ 99· 85 % H 4 % 。 4 ·如申請專利範圍第1或2項之劑量經控制之氣溶膠’其特 徵為，對應之調配成份為： 醣皮質素 0.5% -1·〇%200423969六、申請專利範圍 卵磷脂 異丁烷 5·如前述申請專利範圍任一項中劑量經控制之氣溶膠， 其特徵為該卵磷脂為大豆卵磷脂。 6 ·如申請專利範圍第1或2項之劑量經控制之氣溶膠’其 特徵為，對應之調配成份為： 倍氯美松（Beclomethasone) 0· 1 / 2· 5 乂 大豆卵碟脂 0.05% -5.0% 異丁烷 99· 85 % -92· 5 % 。 7·如申請專利範圍第1或2項之劑量經控制之氣溶膠，其 特徵為，對應之調配成份為： 可滅喘（Budesonide ) 0. 1 % -2. 5 °/〇 大豆卵磷脂 〇· 05 % -5· 0 〇/〇 異丁烷 9 9 · 8 5 % - 9 2. 5 % 。 8·如前述申請專利範圍任一項中劑量經控制之氣溶膠， 厂特欲在於醣皮質素對大豆印磷脂之比例為1:2，較佳為 1:1 ’ 特佳為 1:0. 5。 200423969第13頁 200423969 六、指定代表圖 本案代表圖為：無 ΙΙΙΗϋΙΙ
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10260882A DE10260882B4 (de) | 2002-12-24 | 2002-12-24 | Dosieraerosole mit Sojalecithin als oberflächenaktiver Substanz und dessen Verwendung |
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| Publication Number | Publication Date |
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| TW200423969A true TW200423969A (en) | 2004-11-16 |
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| TW092135946A TW200423969A (en) | 2002-12-24 | 2003-12-18 | Controlled dosage aerosols with lecithin as surface-active agent |
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|---|---|
| US (1) | US20060073103A1 (zh) |
| EP (1) | EP1575559B1 (zh) |
| JP (1) | JP2006517190A (zh) |
| CN (1) | CN1728984A (zh) |
| AT (1) | ATE335467T1 (zh) |
| AU (1) | AU2003300230A1 (zh) |
| DE (2) | DE10260882B4 (zh) |
| DK (1) | DK1575559T3 (zh) |
| ES (1) | ES2270166T3 (zh) |
| IL (1) | IL169356A0 (zh) |
| TW (1) | TW200423969A (zh) |
| WO (1) | WO2004058221A1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5292499A (en) * | 1990-09-11 | 1994-03-08 | University Of Wales College Of Cardiff | Method of preparing medical aerosol formulations including drug dissolved in reverse micelles |
| GB9118830D0 (en) * | 1991-09-03 | 1991-10-16 | Minnesota Mining & Mfg | Medical aerosol formulations |
| US6461591B1 (en) * | 1997-02-05 | 2002-10-08 | Jago Research Ag | Medical aerosol formulations |
| US6017545A (en) * | 1998-02-10 | 2000-01-25 | Modi; Pankaj | Mixed micellar delivery system and method of preparation |
| AU748867B2 (en) * | 1998-07-24 | 2002-06-13 | Jagotec Ag | Medicinal aerosol formulations |
| US6312665B1 (en) * | 1998-12-21 | 2001-11-06 | Generex Pharmaceuticals Incorporated | Aerosol formulations for buccal and pulmonary application |
| DE19911064A1 (de) * | 1999-03-12 | 2000-09-14 | Ig Spruehtechnik Gmbh | Dosieraerosole mit Isobutan als Treibmittel |
-
2002
- 2002-12-24 DE DE10260882A patent/DE10260882B4/de not_active Expired - Fee Related
-
2003
- 2003-12-18 TW TW092135946A patent/TW200423969A/zh unknown
- 2003-12-24 CN CNA2003801071841A patent/CN1728984A/zh active Pending
- 2003-12-24 WO PCT/EP2003/014901 patent/WO2004058221A1/de not_active Ceased
- 2003-12-24 AT AT03799507T patent/ATE335467T1/de not_active IP Right Cessation
- 2003-12-24 ES ES03799507T patent/ES2270166T3/es not_active Expired - Lifetime
- 2003-12-24 US US10/540,648 patent/US20060073103A1/en not_active Abandoned
- 2003-12-24 EP EP03799507A patent/EP1575559B1/de not_active Expired - Lifetime
- 2003-12-24 AU AU2003300230A patent/AU2003300230A1/en not_active Abandoned
- 2003-12-24 DE DE50304615T patent/DE50304615D1/de not_active Expired - Fee Related
- 2003-12-24 JP JP2004563206A patent/JP2006517190A/ja active Pending
- 2003-12-24 DK DK03799507T patent/DK1575559T3/da active
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Also Published As
| Publication number | Publication date |
|---|---|
| IL169356A0 (en) | 2007-07-04 |
| EP1575559B1 (de) | 2006-08-09 |
| ES2270166T3 (es) | 2007-04-01 |
| WO2004058221A1 (de) | 2004-07-15 |
| EP1575559A1 (de) | 2005-09-21 |
| DE10260882A1 (de) | 2004-09-30 |
| US20060073103A1 (en) | 2006-04-06 |
| DE10260882B4 (de) | 2007-02-08 |
| ATE335467T1 (de) | 2006-09-15 |
| JP2006517190A (ja) | 2006-07-20 |
| DK1575559T3 (da) | 2006-11-27 |
| CN1728984A (zh) | 2006-02-01 |
| DE50304615D1 (de) | 2006-09-21 |
| AU2003300230A1 (en) | 2004-07-22 |
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