JP5688799B2 - におい抑制方法 - Google Patents
におい抑制方法 Download PDFInfo
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- JP5688799B2 JP5688799B2 JP2010524712A JP2010524712A JP5688799B2 JP 5688799 B2 JP5688799 B2 JP 5688799B2 JP 2010524712 A JP2010524712 A JP 2010524712A JP 2010524712 A JP2010524712 A JP 2010524712A JP 5688799 B2 JP5688799 B2 JP 5688799B2
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- JP
- Japan
- Prior art keywords
- cyclodextrin
- direct compression
- odor
- olmesartan medoxomil
- compression tablet
- Prior art date
- Legal status (The legal status 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 status listed.)
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- 238000000034 method Methods 0.000 title claims description 17
- 229920000858 Cyclodextrin Polymers 0.000 claims description 66
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- UQGKUQLKSCSZGY-UHFFFAOYSA-N Olmesartan medoxomil Chemical compound C=1C=C(C=2C(=CC=CC=2)C2=NNN=N2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C UQGKUQLKSCSZGY-UHFFFAOYSA-N 0.000 claims description 53
- 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 51
- 239000002051 C09CA08 - Olmesartan medoxomil Substances 0.000 claims description 50
- 229960001199 olmesartan medoxomil Drugs 0.000 claims description 50
- 235000019645 odor Nutrition 0.000 claims description 34
- -1 besylate salt) Chemical compound 0.000 claims description 19
- 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 claims description 19
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- ZKFQEACEUNWPMT-UHFFFAOYSA-N Azelnidipine Chemical compound CC(C)OC(=O)C1=C(C)NC(N)=C(C(=O)OC2CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZKFQEACEUNWPMT-UHFFFAOYSA-N 0.000 claims description 3
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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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- 229950010764 rivoglitazone Drugs 0.000 description 1
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- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- NGHMEZWZOZEZOH-UHFFFAOYSA-N silicic acid;hydrate Chemical compound O.O[Si](O)(O)O NGHMEZWZOZEZOH-UHFFFAOYSA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960004813 trichlormethiazide Drugs 0.000 description 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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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
- A61K31/33—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—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 sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
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- 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
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
(1)メドキソミル基を有する薬物を有効成分として含有し、シクロデキストリンを添加剤として含有することを特徴とする医薬組成物、
(2)メドキソミル基を有する薬物が、オルメサルタンメドキソミルである(1)に記載の医薬組成物、
(3)シクロデキストリンが、α-シクロデキストリン、β-シクロデキストリン、γ-シクロデキストリン及び化学修飾されたシクロデキストリンから選択される化合物の1種又は2種以上である(1)又は(2)に記載の医薬組成物、
(4)シクロデキストリンが、β-シクロデキストリン及び化学修飾されたβ-シクロデキストリンから選択される化合物の1種又は2種以上である(1)又は(2)に記載の医薬組成物、
(5)シクロデキストリンが、β-シクロデキストリンである(1)又は(2)に記載の医薬組成物、
(6)医薬組成物が、固形製剤である(1)乃至(5)のいずれかに記載の医薬組成物、
(7)固形製剤が、散剤、細粒剤、顆粒剤、カプセル剤又は錠剤である(6)に記載の医薬組成物、
(8)固形製剤が、錠剤である(6)に記載の医薬組成物、
(9)錠剤が、1種又は2種以上のフィルムコートの設けられたフィルムコート錠である(8)に記載の医薬組成物、
(10)シクロデキストリンの処方重量比が、オルメサルタンメドキソミルとシクロデキストリンの処方重量比99:1以上である(1)乃至(9)いずれかに記載の医薬組成物、
(11)添加されるシクロデキストリンが、フィルムコート中成分として含有されるフィルムコート錠である(9)に記載の医薬組成物、
(12)シクロデキストリンの処方重量比が、オルメサルタンメドキソミルとシクロデキストリンの処方重量比99:1以上である(11)に記載の医薬組成物、
(13)有効成分として他薬剤の1種又は2種以上をさらに含有する(1)乃至(12)のいずれかに記載の医薬組成物、
(14)他薬剤がアムロジピン(ベシレート塩を含む)、アゼルニジピン及びヒドロクロロチアジドから選択される化合物の1種又は2種以上である(13)に記載の医薬組成物、
(15)高血圧症治療又は予防のための(1)乃至(14)のいずれかに記載の医薬組成物、
(16)臭いの発生が低減された(1)乃至(15)のいずれかに記載の医薬組成物、
(17)発生が低減された臭いが不快な臭いである(16)に記載の医薬組成物、
(18)(1)乃至(15)に記載の医薬組成物による臭い発生の低減方法、
(19)(1)乃至(15)に記載の医薬組成物による不快臭発生の低減方法、
(20)臭い発生を低減化した(1)乃至(15)に記載の医薬組成物の製造方法、
(21)不快臭発生を低減化した(1)乃至(15)に記載の医薬組成物の製造方法、
(22)オルメサルタンメドキソミル含有製剤製造のためのシクロデキストリンの使用、
(23)臭い低減化オルメサルタンメドキソミル含有製剤製造のためのシクロデキストリンの使用等を提供するものである。
なお、分子内にメドキソミル基を有する化合物、例えば高血圧症治療薬であるオルメサルタンメドキソミルは、メドキソミルエステルが徐々に切断され活性本体に変化することにより、低分子の2、3−ブタンジオン(以下、「ジアセチル」という)を発生する化合物である。このジアセチル自体は特異な臭気の原因物質として知られており、メドキソミル基を含有する医薬組成物の臭い原因物質であると考えられている。しかしながら、分子内にメドキソミル基を有する化合物を有効成分とする医薬組成物処方中にシクロデキストリンを加えることにより、臭い低減を図る技術は知られていない。
(実施例1)
オルメサルタンメドキソミルとシクロデキストリン(α-シクロデキストリン((株)林原生物化学研究所)、β-シクロデキストリン(和光純薬工業(株))、γ-シクロデキストリン(和光純薬工業(株))、及びヒドロキシプロピル(HP-)β-シクロデキストリン(ロケットジャパン(株)))をある比率(オルメサルタンメドキソミル/シクロデキストリン=19/1〜1/19)において乳鉢混合し、10gの混合末を得た。
(比較例1)
無処理オルメサルタンメドキソミル原薬
(試験例1)
ガラス瓶に、無処理オルメサルタンメドキソミル原薬(比較例1)または実施例1で製造した、混合末、処理末をオルメサルタンメドキソミルとして100 mg入れ、密栓後、40℃で30分保存した。この後、ガラス瓶を開栓して、被験者6人(A〜F)により下記評価基準で臭いの官能試験を実施した。結果を表1に示す。
<評点> <内容>
0 : 臭わない
1 : やや臭う
2 : 臭う
3 : かなり臭う
ガラス瓶に、無処理オルメサルタンメドキソミル原薬(比較例1)または実施例1で製造した、混合末、処理末、錠剤をオルメサルタンメドキソミルとして100 mg入れ、密栓後、40℃で30分保存した。この後、ガラス瓶を開栓して、被験者6人(A〜F)により前記評価基準で臭いの官能試験を実施した。結果を表2に示す。
ガスクロマトグラフィー用のバイアル(20 mL)に、無処理オルメサルタンメドキソミル原薬(比較例1)または実施例1で調製した混合末をオルメサルタンメドキソミルとして500 mg入れ、密栓後40℃/75%RHで4日間保存した。その後、ヘッドスペースガスをガスクロマトグラフィーにインジェクションし、検出されるガス成分(ジアセチル)の濃度を測定した。結果を表3に示す。なお、ガスクロマトグラフィーの測定条件を下に示す。
〔ガスクロマトグラフィーの測定条件〕
装置:ガスクロマトグラフ 島津GC-2014((株)島津製作所)
検出器:水素炎イオン化検出器
分析カラム:DB-WAX(アジレントテクノロジー(株)、0.53 mm i.d. ×30 m、膜厚:1.00 μm)
カラム温度:50℃
キャリヤーガス:ヘリウム
流量:5.0 mL/min
注入口温度:200℃
検出器温度:230℃
注入量:1.0 mL
(実施例3)
表4に示す処方において、以下の方法にて錠剤を作成した。オルメサルタンメドキソミル、β-シクロデキストリン(日本食品化工(株))、乳糖(ラクトケム(株))、低置換度ヒドロキシプロピルセルロース(信越化学工業(株))、ヒドロキシプロピルセルロース(日本曹達(株))を高速撹拌造粒機(VG-10、パウレック(株))で5分混合後、精製水を適量添加し3分造粒した。得られた造粒物を流動層乾燥機(FLO-5M、フロイント産業(株))で乾燥させた。この乾燥品を目開き約1 mmのスクリーンを付けたコーミル(パウレック(株))で整粒し、結晶セルロース(旭化成ケミカルズ(株))、ステアリン酸マグネシウムを添加し、V型混合機(徳寿製作所(株))で5分間混合した。混合顆粒をロータリー式打錠機(菊水製作所(株))で打錠して錠径8 mmの錠剤を得た(打錠圧:1ton)。得られた錠剤をPress Through Package(以下PTP)包装機にて10錠1シートのPTP包装(材質は無延伸ポリプロピレン、以下CPP)とした。
表5に示す処方において、以下の方法にて錠剤を作成した。オルメサルタンメドキソミル、乳糖(ラクトケム(株))、低置換度ヒドロキシプロピルセルロース(信越化学工業(株))、ヒドロキシプロピルセルロース(日本曹達(株))を高速撹拌造粒機(VG-10、パウレック(株))で5分混合後、精製水を適量添加し3分造粒した。得られた造粒物を流動層乾燥機(FLO-5M、フロイント産業(株))で乾燥させた。この乾燥品を目開き約1 mmのスクリーンを付けたコーミル(パウレック(株))で整粒し、結晶セルロース(旭化成ケミカルズ(株))、ステアリン酸マグネシウムを添加し、V型混合機(徳寿製作所(株))で5分間混合した。混合顆粒をロータリー式打錠機(菊水製作所(株))で打錠して錠径8 mmの錠剤を得た(打錠圧:1ton)。得られた錠剤をPTP包装機にて10錠1シートのPTP包装(材質はCPP)とした。
実施例2、実施例3および比較例2で調製した錠剤(PTP包装品)を25℃/75%RHで1, 2, 3箇月保存した。保存したPTP包装品1錠分をPTPシートから切り取り、ガスクロマトグラフィーのバイアル(約20 mL)に入れ、密栓した。ニードルを用いて錠剤をPTPシートから取り出し、PTPポケット内に溜まったガスをバイアル内で均一に拡散させた。その後、ヘッドスペースガスをガスクロマトグラフィーにインジェクションし、検出されるガス成分(ジアセチル)の濃度を測定した。ガスクロマトグラフィーの測定条件は試験例3と同一とした。結果を表6に示す。
実施例2、実施例3および比較例2で調製した錠剤(PTP包装品)を40℃/75%RHで1箇月保存した。保存したPTP包装品1錠分をPTPシートごと切り取り、ガスクロマトグラフィーのバイアル(約20 mL)に入れ、密栓した。ニードルを用いて錠剤をPTPシートから取り出し、PTPポケット内に溜まったガスをバイアル内で均一に拡散させた。その後、ヘッドスペースガスをガスクロマトグラフィーにインジェクションし、検出されるガス成分の濃度(ジアセチル)を測定した。ガスクロマトグラフィーの測定条件は試験例3と同一とした。結果を表7に示す。
(実施例5)
(実施例6)
比較例2の処方、製法にて未包被錠を製し(杵は錠径7.5 mmのR杵使用)、β-シクロデキストリン(日本食品化工(株))を含有するコーティング液をコーティング装置(ハイコーターミニ、フロイント産業(株))にて、固形分として10 mgもしくは20 mgコーティングした。処方を表8に示す。なお、コーティング液はβ-シクロデキストリン水溶液に、ヒプロメロース、酸化チタン、タルクから成るOpadry OY-S-9607(日本カラコン(株))またはポリビニルアルコール、酸化チタン、タルク、マクロゴールから成るOpadryII 85F48011(日本カラコン(株))を懸濁させ調製した。
(比較例3)
(比較例4)
比較例2の処方、製法にて未包被錠を製し(杵は錠径7.5 mmのR杵使用)、β-シクロデキストリンを含まないコーティング液をコーティング装置(ハイコーターミニ、フロイント産業(株))にて、固形分として10 mgまたは20 mgコーティングした。処方を表9に示す。なお、コーティング液は、ヒプロメロース、酸化チタン、タルクから成るOpadry OY-S-9607(日本カラコン(株))またはポリビニルアルコール、酸化チタン、タルク、マクロゴールから成るOpadryII 85F48011(日本カラコン(株))を精製水に懸濁させ調製した。
Claims (13)
- メドキソミル基を有する薬物を有効成分として含有し、β-シクロデキストリンを添加剤として含有することを特徴とする、該シクロデキストリンの処方重量比が、該メドキソミル基を有する薬物とシクロデキストリンの処方重量比1:1以上である直接打錠剤(但し、フィルムコート錠及び糖衣錠を除く)。
- メドキソミル基を有する薬物が、オルメサルタンメドキソミルである請求項1に記載の直接打錠剤。
- 有効成分として他薬剤の1種又は2種以上をさらに含有する請求項1又は2に記載の直接打錠剤。
- 他薬剤がアムロジピン(ベシレート塩を含む)、アゼルニジピン及びヒドロクロロチアジドから選択される化合物の1種又は2種以上である請求項3に記載の直接打錠剤。
- 高血圧症治療又は予防のための請求項1乃至4のいずれかに記載の直接打錠剤。
- 臭いの発生が低減された請求項1乃至5いずれかに記載の直接打錠剤。
- 発生が低減された臭いが不快な臭いである請求項6に記載の直接打錠剤。
- 請求項1乃至5記載の直接打錠剤による臭い発生の低減方法。
- 請求項1乃至5記載の直接打錠剤による不快臭発生の低減方法。
- 臭い発生を低減化した請求項1乃至5記載の直接打錠剤の製造方法。
- 不快臭発生を低減化した請求項1乃至5記載の直接打錠剤の製造方法。
- β-シクロデキストリンの処方重量比が、オルメサルタンメドキソミルとシクロデキストリンの処方重量比1:1以上であるオルメサルタンメドキソミル含有直接打錠剤(但し、フィルムコート錠及び糖衣錠を除く)製造のためのβ-シクロデキストリンの使用。
- β-シクロデキストリンの処方重量比が、オルメサルタンメドキソミルとシクロデキストリンの処方重量比1:1以上である臭い低減化オルメサルタンメドキソミル含有直接打錠剤(但し、フィルムコート錠及び糖衣錠を除く) 製造のためのβ-シクロデキストリンの使用。
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WO2006123766A1 (ja) * | 2005-05-20 | 2006-11-23 | Daichi Sankyo Company, Limited | デキストロース含有フィルムコーティング製剤 |
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WO2007097452A1 (ja) * | 2006-02-27 | 2007-08-30 | Takeda Pharmaceutical Company Limited | 医薬用ブリスターパッケージ |
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JP2602712B2 (ja) * | 1989-02-14 | 1997-04-23 | メルシャン株式会社 | ヘム鉄含有組成物 |
GB9318880D0 (en) * | 1993-09-11 | 1993-10-27 | Smithkline Beecham Plc | Pharmaceutical composition |
JP2002187842A (ja) * | 2000-12-19 | 2002-07-05 | Toyo Shinyaku:Kk | ケール加工品およびその加工方法 |
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JPH01197432A (ja) * | 1988-01-29 | 1989-08-09 | Takeda Chem Ind Ltd | 糖衣液、糖衣層及びその形成法 |
WO2006123765A1 (ja) * | 2005-05-20 | 2006-11-23 | Daiichi Sankyo Company, Limited | フィルムコーティング製剤 |
WO2006123766A1 (ja) * | 2005-05-20 | 2006-11-23 | Daichi Sankyo Company, Limited | デキストロース含有フィルムコーティング製剤 |
JP2007063142A (ja) * | 2005-08-29 | 2007-03-15 | Izumi Yakuhin Kogyo Kk | 素錠とコーティング層からなる丸剤または錠剤 |
WO2007097452A1 (ja) * | 2006-02-27 | 2007-08-30 | Takeda Pharmaceutical Company Limited | 医薬用ブリスターパッケージ |
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TW201010699A (en) | 2010-03-16 |
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