JP2016500088A5 - - Google Patents
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- JP2016500088A5 JP2016500088A5 JP2015543424A JP2015543424A JP2016500088A5 JP 2016500088 A5 JP2016500088 A5 JP 2016500088A5 JP 2015543424 A JP2015543424 A JP 2015543424A JP 2015543424 A JP2015543424 A JP 2015543424A JP 2016500088 A5 JP2016500088 A5 JP 2016500088A5
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- tolterodine
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 65
- 239000004480 active ingredient Substances 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 22
- 239000011324 bead Substances 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- 229960004045 tolterodine Drugs 0.000 claims description 12
- 229940079593 drugs Drugs 0.000 claims description 11
- 239000011159 matrix material Substances 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- 230000001022 anti-muscarinic Effects 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000012528 membrane Substances 0.000 claims description 8
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 7
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 7
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 206010029446 Nocturia Diseases 0.000 claims description 5
- TWHNMSJGYKMTRB-CDHDNNKHSA-N (2R,3R)-2,3-dihydroxybutanedioic acid;2-[(1S)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-methylphenol Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1([C@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 TWHNMSJGYKMTRB-CDHDNNKHSA-N 0.000 claims description 4
- VUKAUDKDFVSVFT-UHFFFAOYSA-N 2-[6-[4,5-bis(2-hydroxypropoxy)-2-(2-hydroxypropoxymethyl)-6-methoxyoxan-3-yl]oxy-4,5-dimethoxy-2-(methoxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)-5-methoxyoxane-3,4-diol Chemical compound COC1C(OC)C(OC2C(C(O)C(OC)C(CO)O2)O)C(COC)OC1OC1C(COCC(C)O)OC(OC)C(OCC(C)O)C1OCC(C)O VUKAUDKDFVSVFT-UHFFFAOYSA-N 0.000 claims description 4
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 4
- 239000002160 alpha blocker Substances 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 238000000859 sublimation Methods 0.000 claims description 4
- 229960003553 tolterodine tartrate Drugs 0.000 claims description 4
- 239000000651 prodrug Chemical group 0.000 claims description 3
- 229940002612 prodrugs Drugs 0.000 claims description 3
- PUSNGFYSTWMJSK-GSZQVNRLSA-N (2R,3R,4S,5R,6R)-2,3,4-trimethoxy-6-(methoxymethyl)-5-[(2S,3R,4S,5R,6R)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxyoxane;1-[[(2R,3R,4S,5R,6S)-3,4,5-tris(2-hydroxypropoxy)-6-[(2R,3R,4S,5R,6R)-4,5,6-tris(2-hydroxypropoxy)-2-(2-hydroxypropoxymethyl)oxan- Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](OC)O[C@@H]1COC.CC(O)CO[C@@H]1[C@@H](OCC(C)O)[C@H](OCC(C)O)[C@@H](COCC(O)C)O[C@H]1O[C@H]1[C@H](OCC(C)O)[C@@H](OCC(C)O)[C@H](OCC(C)O)O[C@@H]1COCC(C)O PUSNGFYSTWMJSK-GSZQVNRLSA-N 0.000 claims description 2
- 241000220479 Acacia Species 0.000 claims description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 2
- FBPFZTCFMRRESA-KAZBKCHUSA-N D-Mannitol Natural products OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KAZBKCHUSA-N 0.000 claims description 2
- 229960002845 Desmopressin Acetate Drugs 0.000 claims description 2
- 229920001202 Inulin Polymers 0.000 claims description 2
- JYJIGFIDKWBXDU-MNNPPOADSA-N Inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 claims description 2
- 229940029339 Inulin Drugs 0.000 claims description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims description 2
- AIHDCSAXVMAMJH-GFBKWZILSA-N Levan Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(CO[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 AIHDCSAXVMAMJH-GFBKWZILSA-N 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- 239000004373 Pullulan Substances 0.000 claims description 2
- 229920001218 Pullulan Polymers 0.000 claims description 2
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N Raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims description 2
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims description 2
- 229940005550 Sodium alginate Drugs 0.000 claims description 2
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 claims description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N Trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 230000001419 dependent Effects 0.000 claims description 2
- YNKFCNRZZPFMEX-XHPDKPNGSA-N desmopressin acetate trihydrate Chemical group O.O.O.CC(O)=O.C([C@H]1C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSCCC(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](CCCNC(N)=N)C(=O)NCC(N)=O)=O)CCC(=O)N)C1=CC=CC=C1 YNKFCNRZZPFMEX-XHPDKPNGSA-N 0.000 claims description 2
- 238000007710 freezing Methods 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 229940035034 maltodextrin Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000006186 oral dosage form Substances 0.000 claims description 2
- 239000008188 pellet Substances 0.000 claims description 2
- 230000035699 permeability Effects 0.000 claims description 2
- 235000019423 pullulan Nutrition 0.000 claims description 2
- MSXHSNHNTORCAW-UHFFFAOYSA-M sodium 3,4,5,6-tetrahydroxyoxane-2-carboxylate Chemical compound [Na+].OC1OC(C([O-])=O)C(O)C(O)C1O MSXHSNHNTORCAW-UHFFFAOYSA-M 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 229960002613 tamsulosin Drugs 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
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- 229920003169 water-soluble polymer Polymers 0.000 claims description 2
- 210000002700 Urine Anatomy 0.000 claims 1
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Description
実施例１４の凍結乾燥剤形からのｐＨ６．８リン酸緩衝液中における有効成分の放出を図１５に示す。
以下に、本願の当初の特許請求の範囲に記載された発明を付記する。
［１］ 第１医薬有効成分と、１つ以上のマトリックス形成剤と、第２医薬有効成分を含む制御放出ビーズとを含む開放マトリックスネットワークを含む医薬組成物。
［２］ 前記１つ以上のマトリックス形成剤が、レバン、イヌリン、プルラン、ＨＰＭＣ、マルトデキストリン、アカシア、アルギン酸ナトリウムおよびそれらの組み合わせからなる群より選択される、［１］に記載の医薬組成物。
［３］ 前記開放マトリックスネットワークが、マンニトール、トレハロースおよび／またはラフィノースをさらに含む、［１］または［２］に記載の医薬組成物。
［４］ 標準水性媒質中で３０秒以内に溶解する、［１］から［３］のいずれかに記載の医薬組成物。
［５］ 標準水性媒質中で１０秒以内に溶解する、［４］に記載の医薬組成物。
［６］ 前記第１医薬有効成分が、酢酸デスモプレシンである、［１］から［５］のいずれかに記載の医薬組成物。
［７］ 前記制御放出ビーズが、水溶性、水不溶性または水膨潤性の不活性材料のコア（１）を含み、
（ｉ）前記コア（１）上に、実質的に水不溶性または実質的に水溶性のポリマーの任意の内部シールコート層（２）、
（ｉｉ）前記コア（１）または前記内部シールコート層（２）を被覆し、前記第２有効成分を含有する内部薬物含有層（３）、および
（ｉｉｉ）前記内部薬物含有層（３）上に、前記内部薬物含有層（３）からの前記第２有効成分の放出を制御するのに有効なポリマーの外膜層（５）
を有する、［１］から［６］のいずれかに記載の医薬組成物。
［８］ 前記コア（１）が、水溶性球状糖である、［７］に記載の医薬組成物。
［９］ 前記コア（１）が、水膨潤性微結晶セルロースのコアである、［７］に記載の医薬組成物。
［１０］ 前記内部シールコート層（２）の量が、前記制御放出ビーズの約４〜約１５％（ｗ／ｗ）を構成する、［７］から［９］のいずれかに記載の医薬組成物。
［１１］ 前記内部薬物含有層（３）の量が、前記制御放出ビーズの約５〜約２５％（ｗ／ｗ）を構成する、［７］から［１０］のいずれかに記載の医薬組成物。
［１２］ 前記外膜層（５）の量が、前記制御放出ビーズの約２５〜約５５％（ｗ／ｗ）を構成する、［７］から［１１］のいずれかに記載の医薬組成物。
［１３］ 前記外膜層（５）が、ｐＨ依存性の透過性を有するコーティングの付加的なポリマー層（６）で被覆されている、［７］から［１２］のいずれかに記載の医薬組成物。
［１４］ 前記内部シールコート層（２）の実質的に水不溶性のポリマーが、エチルセルロースを含む、［７］から［１３］のいずれかに記載の医薬組成物。
［１５］ 前記内部薬物含有層（３）が、結合剤としてヒドロキシプロピルメチルセルロースを含む、［７］から［１４］のいずれかに記載の医薬組成物。
［１６］ 前記第２有効成分の放出を制御するのに有効な前記外膜層（５）が、ヒドロキシプロピルメチルセルロースとエチルセルロースとの組み合わせを含む、［７］から［１５］のいずれかに記載の医薬組成物。
［１７］ 前記第２有効成分が、抗ムスカリン化合物である、［１］から［１６］のいずれかに記載の医薬組成物。
［１８］ 前記抗ムスカリン化合物が、トルテロジン、トルテロジンの５−ヒドロキシメチル代謝物、トルテロジンの（Ｓ）−エナンチオマー、トルテロジンの（Ｓ）−エナンチオマーの５−ヒドロキシメチル代謝物、トルテロジンのラセミ体、そのプロドラッグ形態、およびそれらの薬理学的に許容される塩から選択される、［１７］に記載の医薬組成物。
［１９］ 前記抗ムスカリン化合物が、トルテロジンまたはその薬理学的に許容される塩である、［１８］に記載の医薬組成物。
［２０］ 前記抗ムスカリン化合物が、酒石酸トルテロジンである、［１９］に記載の医薬組成物。
［２１］ インビトロで放出される酒石酸トルテロジンの割合が、１時間後に約４０％以下、３時間後に約３５〜約８５％、および７時間後に約６５％以上である、［２０］に記載の医薬組成物。
［２２］ 過活動膀胱を治療するための、［１７］から［２１］のいずれかに記載の医薬組成物。
［２３］ 夜間頻尿を伴う過活動膀胱を治療するための、［１７］から［２１］のいずれかに記載の医薬組成物。
［２４］ 女性における夜間頻尿を伴う過活動膀胱を治療するための、［１７］から［２１］のいずれかに記載の医薬組成物。
［２５］ 前記第２有効成分が、選択的α遮断薬である、［１］から［１６］のいずれかに記載の医薬組成物。
［２６］ 前記選択的α遮断薬が、タムスロシン、そのプロドラッグ形態またはその医薬的に許容される塩である、［２５］に記載の医薬組成物。
［２７］ 経口剤形である、［１］から［２６］のいずれかに記載の医薬組成物。
［２８］ 舌下投与に適している、［２７］に記載の医薬組成物。
［２９］ （ｉ）前記制御放出ビーズを、前記第１有効成分および１つ以上のマトリックス形成剤を溶媒中に含む液体調製物と混合して、混合物を形成することと；
（ｉｉ）前記混合物から前記溶媒を昇華させることと
によって得られる、［１］から［２８］のいずれかに記載の医薬組成物。
［３０］ 前記昇華が、前記調製物を凍結乾燥することによって行われる、［２９］に記載の医薬組成物。
［３１］ 第１医薬有効成分と、１つ以上のマトリックス形成剤と、第２医薬有効成分を含有する制御放出ペレットと、溶媒とを含む液体調製物から、溶媒を昇華させることを含む、医薬組成物の調製方法。
［３２］ 前記昇華が、前記液体調製物を凍結乾燥することによって行われる、［３１］に記載の方法。
［３３］ 前記溶媒が、水である、［３１］または［３２］に記載の方法。
［３４］ （ａ）第１有効成分と、第２有効成分を含む制御放出ビーズと、１つ以上のマトリックス形成剤と、溶媒とを含む混合物を調製する工程と、
（ｂ）前記溶液を凍結する工程と、
（ｃ）前記凍結溶液から前記溶媒を昇華させる工程と
を含み、得られた医薬組成物は、標準水性媒質と接触して３０秒以内に崩壊する、医薬組成物の調製方法。
［３５］ 前記組成物が、標準水性媒質と接触して１０秒以内に崩壊する、［３３］に記載の方法。
［３６］ 前記組成物が、［１］から［２８］のいずれかに記載の組成物である、［３１］から［３５］のいずれかに記載の方法。
［３７］ 必要とする対象において過活動膀胱、夜間頻尿またはそれらの組み合わせを治療する方法であって、前記対象に治療有効量の［１７］から［２１］のいずれかに記載の組成物を投与することを含む、方法。
［３８］ 前記対象が女性対象である、［３７］に記載の方法。
［３９］ 必要とする対象において良性前立腺過形成を治療する方法であって、前記対象に治療有効量の［２５］または［２６］に記載の組成物を投与することを含む、方法。
［４０］ 前記対象が男性対象である、［３９］に記載の方法。
The release of the active ingredient in the pH 6.8 phosphate buffer from the lyophilized dosage form of Example 14 is shown in FIG.
The invention described in the scope of the original claims of the present application will be added below.
[1] A pharmaceutical composition comprising an open matrix network comprising a first active pharmaceutical ingredient, one or more matrix forming agents, and controlled release beads comprising a second active pharmaceutical ingredient.
[2] The pharmaceutical composition according to [1], wherein the one or more matrix forming agents are selected from the group consisting of levan, inulin, pullulan, HPMC, maltodextrin, acacia, sodium alginate, and combinations thereof.
[3] The pharmaceutical composition according to [1] or [2], wherein the open matrix network further comprises mannitol, trehalose and / or raffinose.
[4] The pharmaceutical composition according to any one of [1] to [3], which dissolves in a standard aqueous medium within 30 seconds.
[5] The pharmaceutical composition according to [4], which dissolves in a standard aqueous medium within 10 seconds.
[6] The pharmaceutical composition according to any one of [1] to [5], wherein the first pharmaceutical active ingredient is desmopressin acetate.
[7] The controlled release bead comprises a core (1) of a water-soluble, water-insoluble or water-swellable inert material;
(I) an optional inner seal coat layer (2) of a substantially water-insoluble or substantially water-soluble polymer on the core (1);
(Ii) an inner drug-containing layer (3) covering the core (1) or the inner seal coat layer (2) and containing the second active ingredient; and
(Iii) On the inner drug-containing layer (3), an outer membrane layer (5) of a polymer effective for controlling the release of the second active ingredient from the inner drug-containing layer (3)
The pharmaceutical composition according to any one of [1] to [6].
[8] The pharmaceutical composition according to [7], wherein the core (1) is a water-soluble spherical sugar.
[9] The pharmaceutical composition according to [7], wherein the core (1) is a core of water-swellable microcrystalline cellulose.
[10] The pharmaceutical composition according to any one of [7] to [9], wherein the amount of the inner seal coat layer (2) constitutes about 4 to about 15% (w / w) of the controlled release beads. object.
[11] The pharmaceutical composition according to any one of [7] to [10], wherein the amount of the inner drug-containing layer (3) comprises about 5 to about 25% (w / w) of the controlled release beads. object.
[12] The pharmaceutical composition according to any of [7] to [11], wherein the amount of the outer membrane layer (5) comprises about 25 to about 55% (w / w) of the controlled release beads .
[13] The medicament according to any one of [7] to [12], wherein the outer membrane layer (5) is covered with an additional polymer layer (6) having a pH-dependent permeability coating. Composition.
[14] The pharmaceutical composition according to any one of [7] to [13], wherein the substantially water-insoluble polymer of the inner seal coat layer (2) comprises ethyl cellulose.
[15] The pharmaceutical composition according to any one of [7] to [14], wherein the inner drug-containing layer (3) comprises hydroxypropylmethylcellulose as a binder.
[16] The outer membrane layer (5) effective for controlling the release of the second active ingredient contains a combination of hydroxypropylmethylcellulose and ethylcellulose, according to any one of [7] to [15] Pharmaceutical composition.
[17] The pharmaceutical composition according to any one of [1] to [16], wherein the second active ingredient is an antimuscarinic compound.
[18] The antimuscarinic compound includes tolterodine, a 5-hydroxymethyl metabolite of tolterodine, a (S) -enantiomer of tolterodine, a 5-hydroxymethyl metabolite of a (S) -enantiomer of tolterodine, a racemate of tolterodine, its pro The pharmaceutical composition according to [17], which is selected from drug forms and pharmacologically acceptable salts thereof.
[19] The pharmaceutical composition according to [18], wherein the antimuscarinic compound is tolterodine or a pharmacologically acceptable salt thereof.
[20] The pharmaceutical composition according to [19], wherein the antimuscarinic compound is tolterodine tartrate.
[21] The medicament according to [20], wherein the ratio of tolterodine tartrate released in vitro is about 40% or less after 1 hour, about 35 to about 85% after 3 hours, and about 65% or more after 7 hours. Composition.
[22] The pharmaceutical composition according to any one of [17] to [21], for treating overactive bladder.
[23] The pharmaceutical composition according to any one of [17] to [21], for treating overactive bladder accompanied by nocturia.
[24] The pharmaceutical composition according to any one of [17] to [21], for treating overactive bladder accompanied by nocturia in women.
[25] The pharmaceutical composition according to any one of [1] to [16], wherein the second active ingredient is a selective α blocker.
[26] The pharmaceutical composition according to [25], wherein the selective α blocker is tamsulosin, a prodrug form thereof or a pharmaceutically acceptable salt thereof.
[27] The pharmaceutical composition according to any one of [1] to [26], which is an oral dosage form.
[28] The pharmaceutical composition according to [27], which is suitable for sublingual administration.
[29] (i) mixing the controlled release beads with a liquid preparation comprising the first active ingredient and one or more matrix forming agents in a solvent to form a mixture;
(Ii) sublimating the solvent from the mixture;
The pharmaceutical composition according to any one of [1] to [28], obtained by:
[30] The pharmaceutical composition according to [29], wherein the sublimation is performed by lyophilizing the preparation.
[31] A medicament comprising sublimating a solvent from a liquid preparation comprising a first pharmaceutically active ingredient, one or more matrix-forming agents, a controlled release pellet containing a second pharmaceutically active ingredient, and a solvent. Method for preparing the composition.
[32] The method according to [31], wherein the sublimation is performed by freeze-drying the liquid preparation.
[33] The method according to [31] or [32], wherein the solvent is water.
[34] (a) preparing a mixture comprising controlled release beads comprising a first active ingredient, a second active ingredient, one or more matrix forming agents, and a solvent;
(B) freezing the solution;
(C) sublimating the solvent from the frozen solution;
And the resulting pharmaceutical composition disintegrates within 30 seconds upon contact with a standard aqueous medium.
[35] The method of [33], wherein the composition disintegrates within 10 seconds upon contact with a standard aqueous medium.
[36] The method according to any one of [31] to [35], wherein the composition is the composition according to any one of [1] to [28].
[37] A method for treating overactive bladder, nocturia or a combination thereof in a subject in need, wherein the subject comprises a therapeutically effective amount of the composition according to any one of [17] to [21]. Administering.
[38] The method of [37], wherein the subject is a female subject.
[39] A method for treating benign prostatic hyperplasia in a subject in need, comprising administering to the subject a therapeutically effective amount of the composition according to [25] or [26].
[40] The method of [39], wherein the subject is a male subject.
Claims (40)
（ｉ）前記コア（１）上に、実質的に水不溶性または実質的に水溶性のポリマーの任意の内部シールコート層（２）、
（ｉｉ）前記コア（１）または前記内部シールコート層（２）を被覆し、前記第２有効成分を含有する内部薬物含有層（３）、および
（ｉｉｉ）前記内部薬物含有層（３）上に、前記内部薬物含有層（３）からの前記第２有効成分の放出を制御するのに有効なポリマーの外膜層（５）
を有する、請求項１から６のいずれか一項に記載の医薬組成物。 The controlled release beads comprise a core (1) of a water-soluble, water-insoluble or water-swellable inert material;
(I) an optional inner seal coat layer (2) of a substantially water-insoluble or substantially water-soluble polymer on the core (1);
(Ii) an inner drug-containing layer (3) that covers the core (1) or the inner seal coat layer (2) and contains the second active ingredient, and (iii) on the inner drug-containing layer (3) And an outer membrane layer (5) of a polymer effective to control the release of the second active ingredient from the inner drug-containing layer (3).
The pharmaceutical composition according to any one of claims 1 to 6, which has
（ｉｉ）前記混合物から前記溶媒を昇華させることと
によって得られる、請求項１から２８のいずれか一項に記載の医薬組成物。 (I) mixing the controlled release beads with a liquid preparation comprising the first active ingredient and one or more matrix forming agents in a solvent to form a mixture;
29. A pharmaceutical composition according to any one of claims 1 to 28, obtained by (ii) sublimating the solvent from the mixture.
（ｂ）前記溶液を凍結する工程と、
（ｃ）前記凍結溶液から前記溶媒を昇華させる工程と
を含み、得られた医薬組成物は、標準水性媒質と接触して３０秒以内に崩壊する、医薬組成物の調製方法。 (A) preparing a mixture comprising a controlled release bead comprising a first active ingredient, a second active ingredient, one or more matrix-forming agents, and a solvent;
(B) freezing the solution;
(C) sublimating the solvent from the frozen solution, and the resulting pharmaceutical composition is contacted with a standard aqueous medium and disintegrates within 30 seconds.
40. The pharmaceutical composition of claim 39, wherein the subject is a male subject.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN3575/DEL/2012 | 2012-11-21 | ||
| IN3575DE2012 | 2012-11-21 | ||
| IN3947/DEL/2012 | 2012-12-20 | ||
| IN3947DE2012 | 2012-12-20 | ||
| PCT/EP2013/074373 WO2014079922A1 (en) | 2012-11-21 | 2013-11-21 | Composition for immediate and extended release |
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| Publication Number | Publication Date |
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| JP2016500088A JP2016500088A (en) | 2016-01-07 |
| JP2016500088A5 true JP2016500088A5 (en) | 2016-11-17 |
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| JP2015543424A Pending JP2016500088A (en) | 2012-11-21 | 2013-11-21 | Composition for immediate and sustained release |
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| Country | Link |
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| EP (1) | EP2922525A1 (en) |
| JP (1) | JP2016500088A (en) |
| KR (1) | KR20150085826A (en) |
| CN (1) | CN104797240A (en) |
| AR (1) | AR093585A1 (en) |
| AU (1) | AU2013349682A1 (en) |
| BR (1) | BR112015011430A2 (en) |
| CA (1) | CA2891365A1 (en) |
| EA (1) | EA201590805A1 (en) |
| HK (1) | HK1213779A1 (en) |
| IL (1) | IL238648A0 (en) |
| IN (1) | IN2015DN03984A (en) |
| MX (1) | MX2015006399A (en) |
| PH (1) | PH12015501096A1 (en) |
| SG (2) | SG11201503913TA (en) |
| TW (1) | TW201422254A (en) |
| WO (1) | WO2014079922A1 (en) |
| ZA (1) | ZA201503603B (en) |
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| MX2016001030A (en) | 2013-07-23 | 2016-10-07 | Allergan Inc | Methods and compositions comprising desmopressin in combination with a beta-3 adrenergic receptor agonist. |
| KR20150144209A (en) * | 2014-06-16 | 2015-12-24 | 훼링 비.브이. | Pharmaceutical composition comprising stabilized desmopressin or pharmaceutically acceptable salt thereof |
| US10286033B2 (en) * | 2014-11-20 | 2019-05-14 | Serenity Pharmaceuticals, Llc | Methods and compositions comprising desmopressin in combination with an alpha-adrenergic receptor antagonist |
| US9931344B2 (en) | 2015-01-12 | 2018-04-03 | Nano Pharmaceutical Laboratories, Llc | Layered sustained-release microbeads and methods of making the same |
| US20170042806A1 (en) | 2015-04-29 | 2017-02-16 | Dexcel Pharma Technologies Ltd. | Orally disintegrating compositions |
| WO2017039832A1 (en) * | 2015-09-01 | 2017-03-09 | Wellesley Pharmaceuticals, Llc | Extended, delayed and immediate release formulation method of manufacturing and use thereof |
| AU2016331879A1 (en) * | 2015-09-30 | 2018-05-17 | Wellesley Pharmaceuticals, Llc | Composition for reducing the frequency of urination, method of making and use thereof |
| CN108391420A (en) * | 2015-09-30 | 2018-08-10 | 韦尔斯利医药有限公司 | Composition and its preparation method and application for reducing micturition frequency |
| TW201726114A (en) * | 2015-11-23 | 2017-08-01 | 魏斯理製藥公司 | Composition for reducing frequency of urination, method of making and use thereof |
| SG11201806001TA (en) * | 2015-12-18 | 2018-08-30 | Wellesley Pharmaceuticals Llc | Composition for reducing frequency of urination, method of making and use thereof |
| US10076494B2 (en) | 2016-06-16 | 2018-09-18 | Dexcel Pharma Technologies Ltd. | Stable orally disintegrating pharmaceutical compositions |
| JP7042275B2 (en) | 2017-01-11 | 2022-03-25 | フェリング・ベー・フェー | Fast-disintegrating pharmaceutical composition |
| KR20190021180A (en) * | 2017-08-22 | 2019-03-05 | 아주대학교산학협력단 | Pharmaceutical complex formulations for treating neurodegenerative diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4052997A (en) | 1996-07-19 | 1998-02-10 | Clarke-Garegg, Margaret A. | Levan derivatives, their preparation, composition and applications including medical and food applications |
| SE9803871D0 (en) * | 1998-11-11 | 1998-11-11 | Pharmacia & Upjohn Ab | Therapeutic method and formulation |
| GB9908014D0 (en) | 1999-04-08 | 1999-06-02 | Scherer Corp R P | Pharmaceutical compositions |
| EP1064938A1 (en) * | 1999-06-28 | 2001-01-03 | Sanofi-Synthelabo | Pharmaceutical dosage forms for controlled release producing at least a timed pulse |
| US6509040B1 (en) | 2001-06-22 | 2003-01-21 | R.P. Scherer Corporation | Fast dispersing dosage forms essentially free of mammalian gelatin |
| WO2003094886A2 (en) * | 2002-05-07 | 2003-11-20 | Ferring Bv | Desmopressin in an orodispersible dosage form |
| GB0210397D0 (en) | 2002-05-07 | 2002-06-12 | Ferring Bv | Pharmaceutical formulations |
| US8012505B2 (en) | 2003-02-28 | 2011-09-06 | Alk-Abello A/S | Dosage form having a saccharide matrix |
| CN100366294C (en) | 2004-04-30 | 2008-02-06 | 量子高科（北京）研究院有限公司 | Oral cavity quick dissolving preparation and production method thereof |
| EP1629834A1 (en) | 2004-08-27 | 2006-03-01 | KRKA, D.D., Novo Mesto | Sustained release pharmaceutical composition of tolterodine |
| WO2007029087A2 (en) | 2005-09-05 | 2007-03-15 | Ranbaxy Laboratories Limited | Controlled release multiple unit formulations |
| US20090192228A1 (en) | 2008-01-28 | 2009-07-30 | Actavis Group Ptc Ehf | Controlled-Release Tolterodine Compositions and Methods |
| KR20110075011A (en) * | 2008-11-10 | 2011-07-05 | (주)아모레퍼시픽 | Slow-release particle and a production method therefor |
| WO2011013082A1 (en) * | 2009-07-31 | 2011-02-03 | Ranbaxy Laboratories Limited | Multi-layered, multiple unit pharmaceutical compositions |
| BR112012024432A2 (en) | 2010-03-29 | 2016-05-31 | Ferring Bv | fast dissolving pharmaceutical composition |
| JO3112B1 (en) | 2010-03-29 | 2017-09-20 | Ferring Bv | A fast dissolving pharmaceutical composition |
| MX356601B (en) * | 2010-03-30 | 2018-05-29 | Productos Maver S A De C V | Pharmaceutical combination with anti-migraine effect, in solid presentation of extended release. |
| US20120135050A1 (en) * | 2010-07-08 | 2012-05-31 | Wellesley Pharmaceuticals, Llc | Extended-release formulation for reducing the frequency of urination and method of use thereof |
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2013
- 2013-11-11 TW TW102140886A patent/TW201422254A/en unknown
- 2013-11-21 EA EA201590805A patent/EA201590805A1/en unknown
- 2013-11-21 KR KR1020157015219A patent/KR20150085826A/en not_active Application Discontinuation
- 2013-11-21 SG SG11201503913TA patent/SG11201503913TA/en unknown
- 2013-11-21 CA CA2891365A patent/CA2891365A1/en not_active Abandoned
- 2013-11-21 EP EP13792703.4A patent/EP2922525A1/en not_active Withdrawn
- 2013-11-21 IN IN3984DEN2015 patent/IN2015DN03984A/en unknown
- 2013-11-21 CN CN201380060349.8A patent/CN104797240A/en active Pending
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- 2013-11-21 JP JP2015543424A patent/JP2016500088A/en active Pending
- 2013-11-21 MX MX2015006399A patent/MX2015006399A/en unknown
- 2013-11-21 BR BR112015011430A patent/BR112015011430A2/en not_active Application Discontinuation
- 2013-11-21 WO PCT/EP2013/074373 patent/WO2014079922A1/en active Application Filing
- 2013-11-21 AU AU2013349682A patent/AU2013349682A1/en not_active Abandoned
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