JP2015536956A - ヒドロモルホンおよびナロキソンを含む医薬組成物 - Google Patents
ヒドロモルホンおよびナロキソンを含む医薬組成物 Download PDFInfo
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- JP2015536956A JP2015536956A JP2015540971A JP2015540971A JP2015536956A JP 2015536956 A JP2015536956 A JP 2015536956A JP 2015540971 A JP2015540971 A JP 2015540971A JP 2015540971 A JP2015540971 A JP 2015540971A JP 2015536956 A JP2015536956 A JP 2015536956A
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- JP
- Japan
- Prior art keywords
- sustained release
- dosage form
- coated
- hydromorphone
- pharmaceutical dosage
- 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.)
- Granted
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- 229960001375 lactose Drugs 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229940029985 mineral supplement Drugs 0.000 description 1
- 235000020786 mineral supplement Nutrition 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 239000003402 opiate agonist Substances 0.000 description 1
- 201000000988 opioid abuse Diseases 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000009597 pregnancy test Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
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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
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
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Abstract
Description
本願は、2012年11月9日出願の仮特許出願第61/796,390号の米国特許法第119条(e)による利益を主張し、その内容は、参照によって本明細書に組み込まれる。
(a)顆粒と、
(b)(i)ヒドロモルホンまたは薬学的に許容されるその塩、(ii)ナロキソンまたは薬学的に許容されるその塩、(iii)抗酸化化合物、および(iii)キレート化合物を含む、顆粒上にコーティングされた第1の層と、
(c)持続放出性剤を含む、第1の層上にコーティングされた第2の層と
を含む、持続放出性医薬剤形を提供する。
(a)顆粒と、
(b)(i)ヒドロモルホンまたは薬学的に許容されるその塩、(ii)ナロキソンまたは薬学的に許容されるその塩、(iii)抗酸化化合物、および(iii)キレート化合物を含む、顆粒上にコーティングされた第1の層と、
(c)持続放出性剤を含む、第1の層上にコーティングされた第2の層と
を含む、コーティングされたビーズを提供する。
(a)顆粒と、
(b)(i)ヒドロモルホン塩酸塩、(ii)ナロキソン塩酸塩、(iii)抗酸化化合物、および(iii)キレート化合物を含み、(i)および(ii)が約2:1の重量比で存在する、顆粒上にコーティングされた第1の層と、
(c)エチルセルロースを含む、第1の層上にコーティングされた第2の層と、
(d)ポリビニルアルコール−ポリエチレングリコールグラフトコポリマーを含む、第2の層上にコーティングされた第3の層と
を含む、持続放出性医薬剤形を提供する。
1時間で25〜55重量%の薬学的に活性な薬剤、
2時間で45〜75重量%の薬学的に活性な薬剤、
3時間で55〜85重量%の薬学的に活性な薬剤、
4時間で60〜90重量%の薬学的に活性な薬剤、
6時間で70〜100重量%の薬学的に活性な薬剤、
8時間で85重量%超の薬学的に活性な薬剤、
10時間で90重量%超の薬学的に活性な薬剤
である。
1時間で30〜50重量%の薬学的に活性な薬剤、
2時間で50〜70重量%の薬学的に活性な薬剤、
3時間で60〜80重量%の薬学的に活性な薬剤、
4時間で65〜85重量%の薬学的に活性な薬剤、
6時間で75〜95重量%の薬学的に活性な薬剤、
8時間で90重量%超の薬学的に活性な薬剤、
10時間で95重量%超の薬学的に活性な薬剤
である。
1時間で10〜30重量%の薬学的に活性な薬剤、
2時間で34〜54重量%の薬学的に活性な薬剤、
3時間で53〜73重量%の薬学的に活性な薬剤、
4時間で65〜85重量%の薬学的に活性な薬剤、
6時間で75〜95重量%の薬学的に活性な薬剤、
8時間で80〜100重量%の薬学的に活性な薬剤、
10時間で90重量%超の薬学的に活性な薬剤
である。
1時間で5〜45重量%の薬学的に活性な薬剤、
2時間で15〜55重量%の薬学的に活性な薬剤、
3時間で30〜70重量%の薬学的に活性な薬剤、
4時間で35〜75重量%の薬学的に活性な薬剤、
6時間で40〜80重量%の薬学的に活性な薬剤、
8時間で50〜90重量%の薬学的に活性な薬剤、
10時間で60〜100重量%の薬学的に活性な薬剤、
12時間で65〜100重量%の薬学的に活性な薬剤
である。
1時間で8〜42重量%の薬学的に活性な薬剤、
2時間で18〜52重量%の薬学的に活性な薬剤、
3時間で33〜67重量%の薬学的に活性な薬剤、
4時間で38〜72重量%の薬学的に活性な薬剤、
6時間で43〜77重量%の薬学的に活性な薬剤、
8時間で53〜87重量%の薬学的に活性な薬剤、
10時間で63〜97重量%の薬学的に活性な薬剤、
12時間で73〜100重量%の薬学的に活性な薬剤
である。
1時間で15〜37重量%の薬学的に活性な薬剤、
2時間で25〜47重量%の薬学的に活性な薬剤、
3時間で38〜62重量%の薬学的に活性な薬剤、
4時間で42〜66重量%の薬学的に活性な薬剤、
6時間で50〜74重量%の薬学的に活性な薬剤、
8時間で60〜84重量%の薬学的に活性な薬剤、
10時間で68〜92重量%の薬学的に活性な薬剤、
12時間で78〜100重量%の薬学的に活性な薬剤
である。
1時間で19〜33重量%の薬学的に活性な薬剤、
2時間で29〜43重量%の薬学的に活性な薬剤、
3時間で43〜47重量%の薬学的に活性な薬剤、
4時間で47〜61重量%の薬学的に活性な薬剤、
6時間で55〜69重量%の薬学的に活性な薬剤、
8時間で65〜79重量%の薬学的に活性な薬剤、
10時間で73〜87重量%の薬学的に活性な薬剤、
12時間で83〜100重量%の薬学的に活性な薬剤
である。
1時間で1〜15重量%の薬学的に活性な薬剤、
2時間で6〜26重量%の薬学的に活性な薬剤、
3時間で15〜35重量%の薬学的に活性な薬剤、
4時間で25〜45重量%の薬学的に活性な薬剤、
6時間で40〜60重量%の薬学的に活性な薬剤、
8時間で55〜75重量%の薬学的に活性な薬剤、
10時間で60〜80重量%の薬学的に活性な薬剤、
12時間で70〜100重量%の薬学的に活性な薬剤
である。
(実施例)
(1)微結晶性セルロース球(MCC球、Cellets(登録商標)700)、
(2)KPM球と記載される、約20%ポリビニルアルコール−ポリビニルアルコール−ポリエチレングリコールコポリマー(Kollicoat Protect−防湿バリア賦形剤)で予めコーティングされた微結晶性セルロース球(MCC球、Cellets(登録商標)700)、
(3)シリカ球、および
(4)マンニトール−ポリビニルピロリドン球(18/20メッシュ)。
装置:GPCG1 Wursterコーター
ノズル直径:1.0mm
噴霧圧力:2バール
空気速度:6〜7m/s
先の実施例では、いくつかの試験結果を記録した。以下の方法は、試験結果を進展させるのに使用した。
Claims (51)
- 複数のコーティングされたビーズを含む持続放出性医薬剤形であって、コーティングされたビーズのそれぞれが、
(a)顆粒と、
(b)(i)ヒドロモルホンまたは薬学的に許容されるその塩、(ii)ナロキソンまたは薬学的に許容されるその塩、(iii)抗酸化化合物、および(iii)キレート化合物を含む、前記顆粒上にコーティングされた第1の層と、
(c)持続放出性剤を含む、前記第1の層上にコーティングされた第2の層と
を含む、持続放出性医薬剤形。 - (i)および(ii)が、約2:1〜約1:2の重量比で存在する、請求項1に記載の持続放出性医薬剤形。
- (i)が、ヒドロモルホンの薬学的に許容される塩である、請求項1または2に記載の持続放出性医薬剤形。
- (i)が、ヒドロモルホン塩酸塩である、請求項1または2に記載の持続放出性医薬剤形。
- (ii)が、ナロキソンの薬学的に許容される塩である、請求項1から4のいずれかに記載の持続放出性医薬剤形。
- (i)が、ナロキソン塩酸塩である、請求項1から4のいずれかに記載の持続放出性医薬剤形。
- 前記抗酸化化合物が、メタ重亜硫酸ナトリウムを含む、請求項1から6のいずれかに記載の持続放出性医薬剤形。
- 前記キレート剤が、エチレンジニトロ四酢酸を含む、請求項1から7のいずれかに記載の持続放出性医薬剤形。
- 前記キレート剤が、エチレンジニトロ四酢酸二ナトリウム塩を含む、請求項1から7のいずれかに記載の持続放出性医薬剤形。
- 前記持続放出性化合物が、疎水性ポリマー、親水性ポリマー、タンパク質由来の材料、ガム、置換または非置換炭化水素、可消化炭水化物、脂肪酸、脂肪アルコール、脂肪酸のグリセリルエステル、天然油、合成油、天然ワックス、合成ワックス、およびこれらのいずれかの2つ以上の任意の混合物からなる群から選択される、請求項1から9のいずれかに記載の持続放出性医薬剤形。
- 前記持続放出性化合物が、セルロースエーテル、アクリル系ポリマー、アクリル系コポリマー、メタクリル系ポリマー、メタクリル系コポリマー、脂肪アルコール、およびこれらのいずれかの2つ以上の任意の混合物からなる群から選択される、請求項1から9のいずれかに記載の持続放出性医薬剤形。
- 前記持続放出性化合物が、中性アクリル系ポリマー、中性アクリル系コポリマー、中性メタクリル系ポリマー、中性メタクリル系コポリマー、疎水性セルロースエーテル、脂肪アルコール、およびこれらのいずれかの2つ以上の任意の混合物からなる群から選択される、請求項1から9のいずれかに記載の持続放出性医薬剤形。
- 前記持続放出性化合物が、エチルセルロースである、請求項1から9のいずれかに記載の持続放出性医薬剤形。
- 前記顆粒が、コーティングされていない微結晶性セルロース顆粒およびマンニトール−ポリビニルピロリドン顆粒から選択される、請求項1から13のいずれかに記載の持続放出性医薬剤形。
- (d)防湿バリア剤を含む、前記第2の層上にコーティングされた第3の層
をさらに含む、請求項1から14のいずれかに記載の持続放出性医薬剤形。 - 前記防湿バリア剤が、ポリビニルアルコール−ポリエチレングリコールグラフトコポリマーを含む、請求項15に記載の持続放出性医薬剤形。
- カプセルの形態の、請求項1から16のいずれかに記載の持続放出性医薬剤形。
- カプセルが、複数のコーティングされたビーズを含有する、請求項17に記載の持続放出性医薬剤形。
- 前記カプセルが、ヒドロキシプロピルメチルセルロースカプセルである、請求項17または18に記載の持続放出性医薬剤形。
- (a)顆粒と、
(b)(i)ヒドロモルホンまたは薬学的に許容されるその塩、(ii)ナロキソンまたは薬学的に許容されるその塩、(iii)抗酸化化合物、および(iii)キレート化合物を含む、前記顆粒上にコーティングされた第1の層と、
(c)持続放出性剤を含む、前記第1の層上にコーティングされた第2の層と
を含む、コーティングされたビーズ。 - (i)および(ii)が、約2:1〜約1:2の重量比で存在する、請求項20に記載のコーティングされたビーズ。
- (i)が、ヒドロモルホンの薬学的に許容される塩である、請求項20または21に記載のコーティングされたビーズ。
- (i)が、ヒドロモルホン塩酸塩である、請求項20または21に記載のコーティングされたビーズ。
- (ii)が、ナロキソンの薬学的に許容される塩である、請求項20から23のいずれかに記載のコーティングされたビーズ。
- (i)が、ナロキソン塩酸塩である、請求項20から23のいずれかに記載のコーティングされたビーズ。
- 前記抗酸化化合物が、メタ重亜硫酸ナトリウムを含む、請求項20から25のいずれかに記載のコーティングされたビーズ。
- 前記キレート剤が、エチレンジニトロ四酢酸を含む、請求項20から26のいずれかに記載のコーティングされたビーズ。
- 前記キレート剤が、エチレンジニトロ四酢酸二ナトリウム塩を含む、請求項20から26のいずれかに記載のコーティングされたビーズ。
- 前記持続放出性化合物が、疎水性ポリマー、親水性ポリマー、タンパク質由来の材料、ガム、置換または非置換炭化水素、可消化炭水化物、脂肪酸、脂肪アルコール、脂肪酸のグリセリルエステル、天然油、合成油、天然ワックス、合成ワックス、およびこれらのいずれかの2つ以上の任意の混合物からなる群から選択される、請求項20から28のいずれかに記載のコーティングされたビーズ。
- 前記持続放出性化合物が、セルロースエーテル、アクリル系ポリマー、アクリル系コポリマー、メタクリル系ポリマー、メタクリル系コポリマー、脂肪アルコール、およびこれらのいずれかの2つ以上の任意の混合物からなる群から選択される、請求項20から28のいずれかに記載のコーティングされたビーズ。
- 前記持続放出性化合物が、中性アクリル系ポリマー、中性アクリル系コポリマー、中性メタクリル系ポリマー、中性メタクリル系コポリマー、疎水性セルロースエーテル、脂肪アルコール、およびこれらのいずれかの2つ以上またはこれらのいずれかの任意の混合物からなる群から選択される、請求項20から28のいずれかに記載のコーティングされたビーズ。
- 前記持続放出性化合物が、エチルセルロースである、請求項20から28のいずれかに記載のコーティングされたビーズ。
- 前記顆粒が、コーティングされていない微結晶性セルロース顆粒およびマンニトール−ポリビニルピロリドン顆粒から選択される、請求項20から32のいずれかに記載のコーティングされたビーズ。
- (d)防湿バリア剤を含む、前記第2の層上にコーティングされた第3の層
をさらに含む、請求項30から33のいずれかに記載のコーティングされたビーズ。 - 前記防湿バリア剤が、ポリビニルアルコール−ポリエチレングリコールグラフトコポリマーを含む、請求項34に記載のコーティングされたビーズ。
- ヒドロキシプロピルメチルセルロースカプセル内に配置される複数のコーティングされたビーズを含む持続放出性医薬剤形であって、コーティングされたビーズのそれぞれが、
(a)顆粒と、
(b)(i)ヒドロモルホン塩酸塩、(ii)ナロキソン塩酸塩、(iii)抗酸化化合物、および(iii)キレート化合物を含み、(i)および(ii)が約2:1の重量比で存在する、前記顆粒上にコーティングされた第1の層と、
(c)エチルセルロースを含む、第1の層上にコーティングされた第2の層と、
(d)ポリビニルアルコール−ポリエチレングリコールグラフトコポリマーを含む、前記第2の層上にコーティングされた第3の層と
を含む、持続放出性医薬剤形。 - 前記顆粒が、コーティングされていない微結晶性セルロース顆粒である、請求項36に記載のコーティングされたビーズ。
- 前記顆粒が、マンニトール−ポリビニルピロリドン顆粒である、請求項36に記載のコーティングされたビーズ。
- (i)ヒドロモルホンまたは薬学的に許容されるその塩、および(ii)ナロキソンまたは薬学的に許容されるその塩を含む持続放出性剤形の安定性および/または溶解特性を改善するための、抗酸化剤(メタ重亜硫酸ナトリウムなど)およびキレート剤(エチレンジニトロ四酢酸二ナトリウム塩二水和物など)の組合せの使用。
- 前記剤形が、マトリックス剤形である、請求項39に記載の使用。
- 前記剤形が、コーティングされたビーズ剤形である、請求項39に記載の使用。
- 前記剤形が、コーティングされた顆粒剤形である、請求項39に記載の使用。
- 前記剤形が、国際公開第WO2011/141488号に記載の剤形である、請求項39に記載の使用。
- (i)および(ii)が、約2:1〜約1:2の重量比で存在する、請求項39から43のいずれかに記載の使用。
- (i)が、ヒドロモルホンの薬学的に許容される塩である、請求項39から44のいずれかに記載の使用。
- (i)が、ヒドロモルホン塩酸塩である、請求項39から44のいずれかに記載の使用。
- (ii)が、ナロキソンの薬学的に許容される塩である、請求項39から46のいずれかに記載の使用。
- (i)が、ナロキソン塩酸塩である、請求項39から46のいずれかに記載の使用。
- 前記抗酸化化合物が、メタ重亜硫酸ナトリウムを含む、請求項39から48のいずれかに記載の使用。
- 前記キレート剤が、エチレンジニトロ四酢酸を含む、請求項39から49のいずれかに記載の使用。
- 前記キレート剤が、エチレンジニトロ四酢酸二ナトリウム塩を含む、請求項39から49のいずれかに記載の使用。
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PCT/CA2013/000932 WO2014071499A1 (en) | 2012-11-09 | 2013-11-06 | Pharmaceutical compositions comprising hydromorphone and naloxone |
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US20240043447A1 (en) * | 2020-11-13 | 2024-02-08 | Ferrer Internacional, S.A. | Synthesis of hydromorphone base |
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Also Published As
Publication number | Publication date |
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WO2014071499A1 (en) | 2014-05-15 |
PH12015501015A1 (en) | 2015-07-27 |
CN104902880B (zh) | 2017-08-11 |
SA515360408B1 (ar) | 2017-04-03 |
JP2017149725A (ja) | 2017-08-31 |
HK1210042A1 (en) | 2016-04-15 |
US20150283091A1 (en) | 2015-10-08 |
AU2013344281A1 (en) | 2015-05-07 |
US20190224130A1 (en) | 2019-07-25 |
BR112015009871A2 (pt) | 2017-07-11 |
CN104902880A (zh) | 2015-09-09 |
CA2881144A1 (en) | 2014-05-09 |
CA2795324C (en) | 2015-07-14 |
PH12015501015B1 (en) | 2015-07-27 |
KR20150085825A (ko) | 2015-07-24 |
SG11201502752VA (en) | 2015-05-28 |
MX2015005534A (es) | 2016-06-02 |
AU2013344281B2 (en) | 2016-07-28 |
JP6359022B2 (ja) | 2018-07-18 |
KR101774676B1 (ko) | 2017-09-04 |
CA2795324A1 (en) | 2014-05-09 |
MX363142B (es) | 2019-03-12 |
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