TW201231048A - Novel pharmaceutical formulation - Google Patents
Novel pharmaceutical formulation Download PDFInfo
- Publication number
- TW201231048A TW201231048A TW100145934A TW100145934A TW201231048A TW 201231048 A TW201231048 A TW 201231048A TW 100145934 A TW100145934 A TW 100145934A TW 100145934 A TW100145934 A TW 100145934A TW 201231048 A TW201231048 A TW 201231048A
- Authority
- TW
- Taiwan
- Prior art keywords
- liquid composition
- cyclodextrin
- flurbiprofen
- composition
- composition according
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims abstract description 67
- 239000007788 liquid Substances 0.000 claims abstract description 40
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 38
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims abstract description 19
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims abstract description 10
- 239000007864 aqueous solution Substances 0.000 claims abstract description 7
- 229940097362 cyclodextrins Drugs 0.000 claims abstract description 6
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 37
- 229960002390 flurbiprofen Drugs 0.000 claims description 37
- -1 hydroxypropyl Chemical group 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 16
- 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 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 239000000872 buffer Substances 0.000 claims description 9
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 9
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-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)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 GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 8
- 206010006784 Burning sensation Diseases 0.000 claims description 7
- 239000001116 FEMA 4028 Substances 0.000 claims description 7
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- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
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- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
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- 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 claims description 2
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- LDMUAIMVCZGGKX-UHFFFAOYSA-N 1-(3-hydroxypentoxy)pentan-3-ol Chemical class CCC(O)CCOCCC(O)CC LDMUAIMVCZGGKX-UHFFFAOYSA-N 0.000 claims 1
- BEJQXBXPRXFJDP-UHFFFAOYSA-N 3-(3,3-dihydroxypropoxy)propane-1,1-diol Chemical class OC(O)CCOCCC(O)O BEJQXBXPRXFJDP-UHFFFAOYSA-N 0.000 claims 1
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- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims 1
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Description
201231048 六、發明說明: 【發明所屬之技術領域】 本發明係針對一種可用來遞送不可D的化合物諸如 非類固醇抗發炎藥(NS AID)之呈喷霧劑/氣溶膠劑型之醫 藥組成物。更明確言之,本發明係針對一種以說比洛芬 (flurbiprofen)為主之喷霧劑。 【先前技術】 氟比洛芬(flurbiprofen)屬於用來治療發炎及疼痛的 非類固醇抗發炎藥(NSAID)苯基垸酸衍生物家族的成 員。由於具有抗發炎效果而主要用在於類風濕性關節炎 的治療。 氟比洛芬極其不可溶解於低pH之水溶液,其溶解度 隨著pH的增尚而略增。氟比洛芬於不同有機溶劑具有不 等溶解度。已經發展出不同的氟比洛芬劑型及應用,諸 如用於喉喻痛之治療的氟比洛芬喉片。也已開發含氟比 洛芬的漱口劑;以及遞送低(<〇 5% w/v)層級活性成分的 口腔喷霧劑。 已知氟比洛芬在頰腔(口腔)產生燒灼感。此種氟比 洛芬相關的燒灼感極為令人不適,在喉嚨背側引起刺激 性刺痛感’以及咳嗽、作嘔、搔癢或刺激感取決於其濃 度而定°期望減少含氟比洛芬的產品之此種「燒灼感」’ 在此領域已付出相當大量努力。舉例言之,大量努力致 力於發展口味’試圖以各種口味來遮掩燒灼感。喉嚨背 側沒有味覺受器及口味無法遮掩燒灼感,顯然證實欲解 決的問題為氟比洛芬對在喉嚨背側的痛覺受器產生刺激 201231048 效應。 %糊精類乃屬於醣類聚合物的化合物家族。此等糖 類何生物係從不等數目的糖類結合在一起而形成環狀寡 醣。從後文可知,α環糊精係由6員糖環組成,而(3環 糊精及γ環糊精分別地係由7及8員糖環組成。環糊精 類係從澱粉利用酵素轉化產生。環狀結構對環糊精分子 提供以大型表面積,同時也允許其它較小型分子進入其 中而形成包涵體錯合物;如此對環糊精類提供以無限的 潛在用途。環糊精具有藉「囊封」其它分子來形成錯合 物的能力,因而有大量應用用途,諸如用於藥物遞送系 統。 【發明内容】 本發明提供比較目前可得的組成物以每流體體積計 顯著更高濃度之NSAID » 依據本發明之第一態樣,提供一種包括非類固醇抗 發炎藥(NSAID)及一或多種環糊精類之水溶液的液體組 成物。 典型地,該NSAID係選自於由伊布洛芬 (ibuprofen)、酮洛芬(ket〇profen)、氟比洛芬 (flurbiprofen)、雙氯芬酸(diclofenac)、萘普生(napr〇xen) 所組成之組群。較佳地,該NS AID可選自酮洛芬或氟比 洛芬。最佳地,該NS AID為氟比洛芬。 環糊精可選自α、β、γ環糊精及其衍生物。用於本 發明之環糊精類包含天然環糊精類及其衍生物,包含炫 基化及烴基烧基化衍生物及分支環糊精類。特別關注於 -4- 201231048 載有糖殘基之衍生物。於此處 'Μ Μ. ^ ί l-t ^ β用者為沒基乙基、 基丙基(包括2-及3_羥基丙基 柏唞庙々人W 4 )及一羥基丙基醚類、其 相對應之混合醚類及與甲美 如R ώ興甲基或乙基之其它混合醚類,諸 α、β、γ壞糊精之甲基_羥基乙基、乙 乙基-羥基丙基醚類。供此處 "& 土 含甲基α環糊精1基乙A二之特疋環糊精衍生物包 # Λ ^ A 辰糊精、羥基丙基α環糊 常 一 &基丙基ct環糊接、田w η μ- A ^ ^ 精甲基P環糊精、羥基乙基β 衣糊精、羥基丙基β環糊精、_ ^ y ^ —盔基丙基β環糊精、甲 丞γ %糊精、麵基乙基環 -^ Λ ^ γ衣糊精、叙基丙基γ環糊精及 一羥基丙基γί哀糊精。 該NSAID對環糊精 可以是1:〇.7至1:]】 〇·5至1:上.5。該比 ,,. ‘。較佳比為1 : 0.87。為了避免 疑惑,該NS AID對環铷接 2丁 %糊精之比為莫耳比。 組成物包括至少〗〇/ w / _ ± , c〇/ 1/〇w/v層級之NSAID。組成物可含 頁l-5%w/v。組成物較祛 Λ、此 佳3有不多於3.2%之NSAID。組 可含有NSAID的最佳數量為16%*於另一實施 歹· ’較佳含量為3.13〇/〇之NSAID。 典型地’組成物含右松 有緩衝劑。「緩衝劑」一詞係指輔 助將溶液之pH維持在兮經& / 在6亥緩衝糸統的特定範圍内之醫藥 上可接受之賦形劑。 Λ Λ, 緩衝劑之存在濃度例如係於約 ”3%至約5.〇% w/v或約〇 1%至約2 〇% w/v之範圍。醫 :°接又之緩衝劑的非限制性說明例包含磷酸鹽類、 抗壞丘酸鹽類、乙酿瞄 -ι類、檸檬酸鹽類、酒石酸鹽類、 :酸鹽類、丁二酸鹽類、胺基酸類及順丁烯二酸鹽類。 特佳緩衝劑為正磷酸氳二納、轉檬酸或其組合。 -5- 係為約6至約9。 另外,該液體調 ;7.0 至 8.0 ;及’ 201231048 較佳實施例中組成物之pH通常 型地’該液體調配物之pH為約7.4。 物之pH可選自下列範圍:6.5至8.5 至 7.6。 組成物更可含有增稠劑,諸如羥基乙基纖維素、 基丙基甲基纖維素、羧基甲基纖維素鈉或羥基丙基纖 素0 也可存在有小量的其它成分諸如pH調節劑(例 驗’諸如氫氧化納)、乳化劑或分散劑、保藏劑、甜味劑 及調味_]。 依據本發明之較佳組成物包括: (a) 1-5%之氟比洛芬; (b) 5-10%之一或多種α、β、γ環糊精及其衍生物 (c) 至多5 %之一或多種水性緩衝劑; (d) 80-90%之水。 組成物更可包括至多1%之一或多種調味劑,至 0.2°/。之甜味劑及至多0.5%之保藏劑。 組成物更可包括至多0.5 %之增稠劑。 該組成物可呈噴霧劑劑型或作為嗽喉劑或漱口劑 部分使用。較佳劑型係呈可喷霧液劑。 依據本發明之第一態樣’提供一種如本發明之第 態樣所述之醫藥組成物用於喉嚨痛之治療之用途。 依據本發明之第二態樣,提供一種使用如本發明 第一態樣所述之調配物治療喉嘯痛之方法。 依據本發明之第四態樣,提供一種減少因I比洛 典 配 \2 羥 維 如 多 之 之 芬 -6 - 201231048 所引起的刺激或燒灼感之方法,該方法包括對 予依據本發明之第〜態樣之組成物。 依據本發明之第五態樣,提供—種改良 溶液中之安定性之方法,立中兮,々 洛芬於 液之載有經基的化合物,及其中該方法包括 乍為溶 載有羥基的化合物之前,.飞人兮备 — h σ該等 驟。 之刖,混合該…芬與環糊精之步 典型地含有氟比洛芬之溶液為水溶液。 態樣之 典型地該方法係用以形成依據本發明之第 組成物。 【實施方式】 將藉下列具體實施例例示說明本發明。 實施例1 1.683克之氟比洛芬及6 265克之ρ環糊精(β 重加至100毫升量瓶内。將50毫升之ρΗ 7 4緩衝液添 加至該量瓶及震搖而懸浮及濕潤該β環糊精及氟比洛 芬。以激烈攪拌逐滴添加1Μ氫氧化鈉(水溶液)直至氟比 洛芬及Ρ環糊精完全溶解。需6毫升之氫氧化鈉溶液來 溶解該β環糊精及氟比洛芬。溶液以純水調整至1 〇 〇毫 升及徹底混合。溶液為透明無色。pH經測量發現恰為ρΗ 7.40。 以類似方式製備額外實施例。此等組成物之細節列 舉如下。 201231048
微升8.75毫克。 第3圖例示說明於較高濃度氟比洛芬時觀察得的最 201231048 低要求pH之變化。該快速下降的中心係在β環糊精: 氟比洛芬之比=0.95: 1至1.05: 1。 第4及5圖例示說明本發明之實施例2及4之組成 物的改良安定性。即便於40°C /7 5 %相對濕度(RH)長達52 週氟比洛芬也未見顯著降解。結果列舉於下表。含有乙 醇之試驗組成物顯示兩週内有10%至14%的降解。 實施例4 實施例2 時間點 氟比洛芬含量(%毫克/毫升) 氟比洛芬含量(%毫克/毫升) 儲存條件 0 1.6788 1.6997 25〇C/60%RH 2 1.7014 1.6863 4 1.7029 1.6989 8 1.6456 1.7027 12 1.7011 1.7024 26 1.7142 1.6886 39 1.7365 1.7115 52 1.6832 1.6908 30〇C/65%RH 2 1.6912 1.6939 4 1.6889 1.6941 8 1.6698 1.6622 12 1.6945 1.6979 26 1.7204 1.7117 39 1.6982 1.7115 52 1.6870 1.6922 40〇C/75%RH 2 1.6798 1.7004 4 1.7028 1.6904 8 1.7022 1.7019 12 1.6992 1.7286 26 1.7030 1.7060 52 1.6845 1.6930 201231048 本發明之優點為提供一種用在喉嘴喷霧產品之澄 的物理上及化學上安定的具有足夠濃度之氟比洛芬 液,此處臨床上最佳劑量的活性醫藥物質可藉泵浦或 它喷霧機構以小量體積之(濃縮)溶液遞送/計量及a製 方法。此種溶液並不具有組成物於較高pH時,亦^高 約pH 8時,所致的非期望口味。 本發明之又再一優點為免除使用醇類作為助溶劑 如此導致具有改良安定性的組成物。於含有具羧酸部 的NS AID之組成物中存在有醇類,結果導致產生其相 應的酯》本發明之組成物於非為溶劑之其它含羥基化 物存在下’確實具有出人意表的安定性。例如,用於 體實施例的調味系統不會造成較高濃度的氟比洛芬 解。 並未悖離此處所述本發明之範圍可做出額外修改 改良。 【圖式簡單說明】 第1圖顯示α、β、γ環糊精; 第2圖顯示於14.58毫克/毫升氟比洛芬濃度,針 不同β環糊精:氟比洛芬比達成溶液澄清所要求的最 ΡΗ ; 第3圖顯示於31.25毫克/毫升氟比洛芬濃度,針 不同β環糊精:氟比洛芬比達成溶液澄清所要求的最 ΡΗ ; 第4圖顯示對本發明之實例4之降解研究;及 第5圖顯示對本發明之實例5之降解研究。 清 溶 其 備 於 分 對 合 具 降 及 對 低 對 低 -10- 201231048 【主要元件符號說明】 無。 -11
Claims (1)
- 201231048 七、申請專利範圍· 1. 一種液體組成物,其係包括非類固醇抗發炎藥 (NSAID)及一或多種環糊精類之水溶液。 2·如申請專利範圍第1項之液體組成物,其中該NS AID 係選自於由伊布洛芬(ibuprofen)、酮洛芬 (ketoprofen)、氣比洛芬(flurbiprofen)、雙氣芬酸 (diclofenac)、萘普生(naproxen)所組成之組群。 3.如申請專利範圍第2項之液體組成物,其中該NS AID 係選自酮洛芬或氟比洛芬。 4 ·如前述申請專利範圍中任一項之液體組成物,其中該 環糊精係選自a、β、γ環糊精及其衍生物,其包含天 然環糊精類及其衍生物,包含烷基化及烴基烷基化衍 生物及分支環糊精類、栽有糖殘基之衍生物。 5.如前述申請專利範圍中任一項之液體組成物,其中該 裒糊精係選自於由下列所組成之組群:羥基乙基、羥 基丙基(包括2-及3·羥基丙基)及二羥基丙基醚類、其 相對應之混合峻類及與甲基或乙基之其它混合醚 ^諸如α、β、γ環糊精之曱基羥基乙基、乙基-羥 乙基及乙基-羥基丙基醚類。 6·如申請專利範圍第5担 .., ^項之液體組成物,其中該環糊精 何生物係選自於由 卜列所組成之組群:甲基α環糊 積、羥基乙基α環糊接 玉甘 州精、羥基丙基α環糊精、二羥基 内基ex環糊精、甲其 额甘 環糊精、羥基乙基β環糊精、 赵基丙基β環糊精、_ -^ ''羥基丙基β環糊精、甲基γ環 糊精、羥基乙基 衣糊精、羥基丙基γ環糊精及二羥 201231048 基丙基γ環糊精。 7 ·如前述申請專利範圍中任一項之液體組成物,其中該 NSAID對環糊精之比為1 : 0.5至1 : 1.5。 8.如申請專利範圍第7項之液體組成物’其中該比為 1: 0.7至 1: 11β 9·如申請專利範圍第8項之液體組成物,其中該較佳比 為 1 ·· 0.87。 10. 如前述申請專利範圍中任一項之液體組成物,其中該 組成物包括至少1Q/()W/V層級之該NSAID。 11. 如申請專利範圍第10項之液體組成物,其中該組成 物包括至少l_5%w/v層級之該NSAID。 12·如前述申請專利範圍中任一項之液體組成物,其中該 組成物含有不多於3.2%之NS AID。 13. 如申請專利範圍第η項之液體組成物,其中該NS AID 之含1為1.6%w/v。 14. 如申請專利範圍第丨2項之液體組成物,其中該NSAID 之含量為3.13% w/v。 1 5 ·如前述申請專利範圍中任一項之液體組成物,其中該 組成物更含有一醫藥上可接受之緩衝劑。 16. 如申請專利範圍第13項之液體組成物,其中該緩衝 劑係以約0.03%至約5.0% w/v之範圍之濃度存在。 17. 如申凊專利範圍第14項之液體組成物,其中該緩衝 劑係以約0.1 %至約2.0% w/v之濃度存在。 18. 如申請專利範圍第15至17項中任一項之液體組成 物,其中該醫藥上可接受之緩衝劑包含磷酸鹽類、抗 -13- 201231048 壞血酸鹽類、乙酸鹽類、檸檬酸鹽類、酒石酸鹽類、 乳酸鹽類、丁二酸鹽類、胺基酸類及順丁稀二酸鹽類。 1 9.如申請專利範圍第1 8項之液體組成物,其中該緩衝 劑為正麟酸氫二鈉、棒檬酸或其組合。 2〇·如前述申請專利範圍中任一項之液體組成物,其中該 組成物之pH為約6至約9。 2 1.如申請專利範圍第20項之液體組成物,其中該液體 組成物之pH係選自下列範圍:6.5至8.5; 7.0至8.0 ; 及 7.2 至 7.6 。 22·如申請專利範圍第21項之液體組成物,其中該液體 組成物之pH為約7.4。 23. 如前述申請專利範圍中任一項之液體組成物,其中該 組成物更含有增稠劑,諸如羥基乙基纖維素、羥基丙 基甲基纖維素、羧基甲基纖維素鈉或羥基丙基纖維 素。 24. 如前述申請專利範圍中任一項之液體組成物,其中也 可存在有其它組成分,諸如pH調節劑(例如鹼,諸如 氫氧化鈉)、乳化劑或分散劑、保藏劑、甜味劑、及 調味劑。 25. 如則述申請專利範圍中任一項之液體組成物,其中該 組成物包括: (a) l-5%之氟比洛芬; (b) 5-10%之一或多種α、β、γ環糊精及其衍生物; (c) 至多5 %之一或多種水性緩衝劑; (d) 80-90%之水。 -14- 201231048 26.如則述申請專利範圍中任一項之液體組成物其中 、’且成物更包括至多1 %之一或多種調味劑,至多〇. 之甜味劑及至多〇·5%之保藏劑。 .如則述申請專利範圍中任一項之液體組成物,其中 組成物更包括至多0.5 %之增稠劑。 8’如則述申請專利範圍中任一項之液體組成物,其中 、’且成物係呈喷霧劑劑型或作為嗷喉劑或嗷口劑之 分使用。 •如申凊專利範圍第28項之液體組成物,其中該劑 係呈可噴霧液體。 3〇‘~種如前述申請專利範圍中任一項之液體組成物 用途’其係用於喉嚨痛之治療。 種^療喉嚨痛之方法,其係使用如申請專利範圍 1至29項中任一項之液體組成物。 32. —種減少因氟比洛芬所引起的刺激或燒灼感之 法,其包括對一個體投予如申請專利範圍第i至 項中任一項之液體組成物。 33. ~種改良氟比洛芬於溶液中之安定性之方法,其中 溶液包括並非用作為溶液之載有羥基的化合物及 I該方法包括於添加該等載有羥基的化合物之前, &該氟比洛芬與環糊精之步驟。 :申:月專利範圍第33項之方法,其中含有該氟比 >之溶液為水溶液。 35.如申請專利範圍第33或34項之方法’其中該方法 用來形成依據本發明之第一態樣之組成物。 該 2% 該 該 部 型 之 第 方 29 該 其 混 洛 係 -15-
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US20170290765A1 (en) * | 2014-09-17 | 2017-10-12 | Epizyme, Inc. | Injectable formulations for treating cancer |
KR102545748B1 (ko) * | 2017-12-26 | 2023-06-21 | 한미약품 주식회사 | 플루르비프로펜 함유 스프레이 조성물 및 그 제조방법 |
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US20220125751A1 (en) * | 2019-02-11 | 2022-04-28 | Reckitt Benckiser Health Limited | Novel composition |
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CN110283259B (zh) * | 2019-07-03 | 2021-12-10 | 宁夏医科大学 | 一种解热镇痛布洛芬-β-环糊精第一面衍生物及其制备方法 |
WO2021222888A1 (en) * | 2020-05-01 | 2021-11-04 | University Of Southern California | Cyclodextrin based anti-microbial therapy |
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IT1243342B (it) * | 1990-07-13 | 1994-06-10 | Farcon Ag | Composizioni farmaceutiche orali liquide ad attivita' antiinfiammatoria |
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