JP6133772B2 - 痛み治療用の医薬配合物 - Google Patents
痛み治療用の医薬配合物 Download PDFInfo
- Publication number
- JP6133772B2 JP6133772B2 JP2013514579A JP2013514579A JP6133772B2 JP 6133772 B2 JP6133772 B2 JP 6133772B2 JP 2013514579 A JP2013514579 A JP 2013514579A JP 2013514579 A JP2013514579 A JP 2013514579A JP 6133772 B2 JP6133772 B2 JP 6133772B2
- Authority
- JP
- Japan
- Prior art keywords
- administration
- pain
- formulation
- pharmaceutical composition
- addition salt
- 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.)
- Expired - Fee Related
Links
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 34
- 230000036407 pain Effects 0.000 title claims description 27
- 238000011282 treatment Methods 0.000 title claims description 13
- 239000000203 mixture Substances 0.000 claims description 64
- 238000009472 formulation Methods 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 46
- 239000002253 acid Substances 0.000 claims description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 12
- 229960003299 ketamine Drugs 0.000 claims description 10
- KWTWDQCKEHXFFR-SMDDNHRTSA-N tapentadol Chemical compound CN(C)C[C@H](C)[C@@H](CC)C1=CC=CC(O)=C1 KWTWDQCKEHXFFR-SMDDNHRTSA-N 0.000 claims description 9
- 206010065390 Inflammatory pain Diseases 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 208000021722 neuropathic pain Diseases 0.000 claims description 8
- 208000000094 Chronic Pain Diseases 0.000 claims description 6
- 208000005298 acute pain Diseases 0.000 claims description 6
- 230000002195 synergetic effect Effects 0.000 claims description 6
- 206010058019 Cancer Pain Diseases 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 5
- 208000009935 visceral pain Diseases 0.000 claims description 5
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- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 238000013270 controlled release Methods 0.000 claims description 4
- 238000007912 intraperitoneal administration Methods 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 238000001361 intraarterial administration Methods 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 238000007913 intrathecal administration Methods 0.000 claims description 2
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- 238000000034 method Methods 0.000 description 11
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- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 7
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
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- 238000004458 analytical method Methods 0.000 description 3
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- 239000001506 calcium phosphate Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
- VCKPUUFAIGNJHC-UHFFFAOYSA-N 3-hydroxykynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC(O)=C1N VCKPUUFAIGNJHC-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- HDHQZCHIXUUSMK-UHFFFAOYSA-N 4-hydroxy-2-quinolone Chemical compound C1=CC=C2C(O)=CC(=O)NC2=C1 HDHQZCHIXUUSMK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
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- 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
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- SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical compound C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 description 1
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- 229920006395 saturated elastomer Polymers 0.000 description 1
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- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 229950009825 selfotel Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 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
- 239000004208 shellac Substances 0.000 description 1
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- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
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- GRSDSTMFQHAESM-UHDJGPCESA-M sodium;3-[(e)-3-anilino-3-oxoprop-1-enyl]-4,6-dichloro-1h-indole-2-carboxylate Chemical compound [Na+].[O-]C(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=CC=C1 GRSDSTMFQHAESM-UHDJGPCESA-M 0.000 description 1
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- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
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- 230000009044 synergistic interaction Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
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- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 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
- 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
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/13—Amines
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
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- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(a)次式(I):
(b)少なくとも1種のNMDAアンタゴニストと
を含む医薬配合物に関する。
(1R,2R)−3−(3−ジメチルアミノ−1−エチル−2−メチルプロピル)−フェノール、
(1S,2S)−3−(3−ジメチルアミノ−1−エチル−2−メチルプロピル)−フェノール、
(1R,2S)−3−(3−ジメチルアミノ−1−エチル−2−メチルプロピル)−フェノール、
(1S,2R)−3−(3−ジメチルアミノ−1−エチル−2−メチルプロピル)−フェノール、
及びそれらの任意の混合物
から選択される。
(1R,2R)−3−(3−ジメチルアミノ−1−エチル−2−メチルプロピル)−フェノール、及び
(1S,2S)−3−(3−ジメチルアミノ−1−エチル−2−メチルプロピル)−フェノール、並びに
それらの任意の混合物
から選択される。
(a)次式(I’)の化合物(1R,2R)−3−(3−ジメチルアミノ−1−エチル−2−メチルプロピル)−フェノール
ラットでのランダルセリット試験
本発明の医薬組成物の相加効果(相乗効果)に至る成分(a)及び(b)の重量比は、炎症性の痛み又は神経障害性の痛みのモデルにおいて機械的痛覚過敏を評価するのに適合できる機械的痛覚試験である、Arch.Int.Pharmacodyn.,1957,111:409〜419に記載されたランダル及びセリットの試験により決定できる。この文献の各部は引用によりここに含まれ、本明細書の一部をなす。
Claims (12)
- 前記式(I’)の化合物の酸付加塩がその塩酸塩付加塩である、請求項1に記載の医薬組成物。
- 前記成分(b)の酸付加塩がその塩酸塩付加塩である、請求項1または2に記載の医薬組成物。
- 前記成分(a)及び(b)は、前記配合物が患者への投与に対して相乗効果を発揮する重量比で存在する、請求項1〜3のいずれか1つに記載の医薬組成物。
- 請求項1〜4のいずれか1つに記載の医薬配合物と、1種以上の助剤とを含む医薬組成物。
- 請求項1〜4のいずれか1つに記載の医薬組成物と、任意に1種以上の助剤とを含む製剤。
- 経口投与、静脈内投与、動脈内投与、腹腔内投与、皮内投与、経皮投与、くも膜下投与、筋肉内投与、鼻腔内投与、経粘膜投与、皮下投与又は直腸投与に好適であることを特徴とする、請求項6に記載の製剤。
- 前記成分(a)及び(b)の一方又は両方が放出制御形態で存在する、請求項6又は7に記載の製剤。
- 前記医薬配合物の成分(a)及び成分(b)が同時に又は連続的に投与され、ここで、該成分(a)を該成分(b)の前又は後に投与されてよく、該成分(a)又は(b)が同一の又は異なる投与経路により投与される、請求項6〜8のいずれか1つに記載の製剤。
- 痛みの治療用の、請求項1〜5のいずれか1つに記載の医薬組成物。
- 前記痛みが炎症性痛、神経障害性痛、急性痛、慢性痛、内臓痛、偏頭痛の痛み及び癌の痛みから選択される、請求項10に記載の医薬組成物。
- 前記痛みが炎症性痛である、請求項11に記載の医薬組成物。
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CA (1) | CA2796774C (ja) |
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Cited By (1)
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JP2017141277A (ja) * | 2010-06-15 | 2017-08-17 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 痛み治療用の医薬配合物 |
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