JP4943550B2 - 医薬組成物 - Google Patents
医薬組成物 Download PDFInfo
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- JP4943550B2 JP4943550B2 JP2011137329A JP2011137329A JP4943550B2 JP 4943550 B2 JP4943550 B2 JP 4943550B2 JP 2011137329 A JP2011137329 A JP 2011137329A JP 2011137329 A JP2011137329 A JP 2011137329A JP 4943550 B2 JP4943550 B2 JP 4943550B2
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- Prior art keywords
- midazolam
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- unit dose
- Prior art date
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- GWUSZQUVEVMBPI-UHFFFAOYSA-N nimetazepam Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1 GWUSZQUVEVMBPI-UHFFFAOYSA-N 0.000 description 1
- 229950001981 nimetazepam Drugs 0.000 description 1
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 1
- 229960001454 nitrazepam Drugs 0.000 description 1
- ZAQDQFFQEKUULQ-UHFFFAOYSA-N nitrooxy(phenyl)mercury;phenylmercury;hydrate Chemical compound O.[Hg]C1=CC=CC=C1.[O-][N+](=O)O[Hg]C1=CC=CC=C1 ZAQDQFFQEKUULQ-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- AKPLHCDWDRPJGD-UHFFFAOYSA-N nordazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)CN=C1C1=CC=CC=C1 AKPLHCDWDRPJGD-UHFFFAOYSA-N 0.000 description 1
- 229960002640 nordazepam Drugs 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
- 229960004535 oxazepam Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- 229960005118 oxymorphone Drugs 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229940049721 phenazepam Drugs 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- XEBWQGVWTUSTLN-UHFFFAOYSA-M phenylmercury acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1 XEBWQGVWTUSTLN-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- MFZOSKPPVCIFMT-UHFFFAOYSA-N pinazepam Chemical compound C12=CC(Cl)=CC=C2N(CC#C)C(=O)CN=C1C1=CC=CC=C1 MFZOSKPPVCIFMT-UHFFFAOYSA-N 0.000 description 1
- 229960002034 pinazepam Drugs 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 229960004856 prazepam Drugs 0.000 description 1
- CNWSHOJSFGGNLC-UHFFFAOYSA-N premazepam Chemical compound C=1N(C)C(C)=C2C=1NC(=O)CN=C2C1=CC=CC=C1 CNWSHOJSFGGNLC-UHFFFAOYSA-N 0.000 description 1
- 229950003432 premazepam Drugs 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229940095050 propylene Drugs 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 229960001964 quazepam Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229960003394 remifentanil Drugs 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 239000011734 sodium Substances 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
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- PESXGULMKCKJCC-UHFFFAOYSA-M sodium;4-methoxycarbonylphenolate Chemical compound [Na+].COC(=O)C1=CC=C([O-])C=C1 PESXGULMKCKJCC-UHFFFAOYSA-M 0.000 description 1
- IXMINYBUNCWGER-UHFFFAOYSA-M sodium;4-propoxycarbonylphenolate Chemical compound [Na+].CCCOC(=O)C1=CC=C([O-])C=C1 IXMINYBUNCWGER-UHFFFAOYSA-M 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
- 229960004739 sufentanil Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000002426 superphosphate Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 229960003188 temazepam Drugs 0.000 description 1
- IQWYAQCHYZHJOS-UHFFFAOYSA-N tetrazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CCCCC1 IQWYAQCHYZHJOS-UHFFFAOYSA-N 0.000 description 1
- 229960005214 tetrazepam Drugs 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
- 229960004906 thiomersal Drugs 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
- 229960004380 tramadol Drugs 0.000 description 1
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 description 1
- 229960003386 triazolam Drugs 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
- A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
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- 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
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- Neurology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Anesthesiology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
ある範囲の製剤を調製した。これらは以下の組成を有する:
安定性に対するpHの効果をさらに検討するために、実施例1で論じたものに対する代替の一連の製剤を調製した。pH8.5で溶解しているミダゾラムを含む一連の組成物を以下の2つの方法に従って作製した。
実施例2で論じた製剤のいくつかの安定性を、市販されている4.5〜5.5のpHを有するEpistatus製品(比較例)の2つの試料と比較した。これらの試料を、40℃の温度、75%の相対湿度下で3カ月間貯蔵した。貯蔵後、試料を分析した。不純物スクシニルミダゾラム(SMA、SMB)および全不純物の濃度%を図5aおよび図5bにそれぞれ示す。これから分かるように、本発明の高いpHの製剤は、45℃の温度、75%の相対湿度下で3カ月間貯蔵した後、著しく少ない量の不純物しか含有していなかった。
本発明の組成物のフラックス速度対低pH(約5)比較例製剤のフラックス速度を、フランツセルを用いて測定した。フラックス速度を、250μm膜を備えたRotulex No.18フランツセルと紫外-可視分光光度計(Spectronic Biomate, Thermo Electron Limited, Cambridge, UK)を用い、活性剤を無限投与して21℃で測定した。
実施例4で論じた比較例製剤および実施例2で調製した組成物のいくつかを用いて追加のフランツセル試験(Franz cell testing)を実施した。
Claims (35)
- pHが8以上であり、粘度が200〜400CPである、ミダゾラムおよび薬学的に許容される担体を含む、患者に投与するための液体組成物であって、前記組成物が200mg/ml未満のシクロデキストリンを含み、前記ミダゾラムの少なくとも50%が溶解して存在する、液体組成物。
- 口腔、経鼻、経直腸および/または舌下経路で投与するためである、請求項1に記載の液体組成物。
- pHが8〜11である、請求項1または2に記載の液体組成物。
- pHが8〜10.5である、請求項1から3のいずれか一項に記載の液体組成物。
- pHが8〜10である、請求項1から4のいずれか一項に記載の液体組成物。
- 前記ミダゾラムの少なくとも90%が溶解して存在する、請求項1から5のいずれか一項に記載の液体組成物。
- 前記ミダゾラムの少なくとも98%が溶解して存在する、請求項1から6のいずれか一項に記載の液体組成物。
- ミダゾラムの濃度が5mg/ml〜20mg/mlである、請求項1から7のいずれか一項に記載の組成物。
- ミダゾラムの濃度が6mg/ml〜15mg/mlである、請求項1から8のいずれか一項に記載の組成物。
- ミダゾラムの濃度が7.5mg/ml〜12.5mg/mlである、請求項1から9のいずれか一項に記載の組成物。
- 粘度が250CP〜350CPである、請求項1から10のいずれか一項に記載の組成物。
- 粘度が270CP〜330CPである、請求項1から11のいずれか一項に記載の組成物。
- 増粘成分をさらに含む、請求項1から12のいずれか一項に記載の組成物。
- 50mg/ml以下のシクロデキストリンを含む、請求項1から13のいずれか一項に記載の組成物。
- シクロデキストリンを含まない、請求項1から14のいずれか一項に記載の組成物。
- 緩衝剤をさらに含む、請求項1から12のいずれか一項に記載の組成物。
- 前記緩衝剤が、リン酸緩衝剤、グリシン/NaOH緩衝剤または炭酸もしくは重炭酸緩衝剤あるいはそれらの混合物である、請求項16に記載の組成物。
- 甘味剤、香味増進剤、保存剤および/または抗真菌薬をさらに含む、請求項1から17のいずれか一項に記載の組成物。
- 前記担体が、水、エタノール、グリセリン、グリセロール、ポリエチレングリコール、プロピレングリコールまたはそれらの混合物を含む、請求項1から18のいずれか一項に記載の組成物。
- 追加の治療剤をさらに含む、請求項1から19のいずれか一項に記載の組成物。
- てんかん発作を治療するかつ/またはある程度の麻酔を誘発させるのに使用するための請求項1から20のいずれか一項に記載の組成物。
- 請求項1から21のいずれか一項に記載の組成物の単位用量製剤。
- 0.1〜10mlの製剤を含む、請求項22に記載の単位用量製剤。
- 0.2〜5mlの製剤を含む、請求項22または23に記載の単位用量製剤。
- 0.5〜2mlの製剤を含む、請求項22から24のいずれか一項に記載の単位用量製剤。
- 使い捨て投与手段内に含有される、請求項22から25のいずれか一項に記載の単位用量製剤。
- 前記使い捨て投与手段が点滴器である、請求項22から26のいずれか一項に記載の単位用量製剤。
- 請求項1から21のいずれか一項に記載の組成物または請求項22から27のいずれか一項に記載の単位用量製剤を含むキット。
- 追加の治療剤をさらに含む、請求項28に記載のキット。
- 前記追加の治療剤が単位用量製剤で提供される、請求項29に記載のキット。
- てんかん発作を治療するかつ/または患者においてある程度の麻酔を誘発させるのに使用するための、請求項1から21のいずれか一項に記載の組成物。
- 前記患者が14才以下の年齢である、請求項31に記載の組成物。
- 前記患者に追加の治療剤を同時または逐次的に投与する、請求項31または32に記載の組成物。
- 追加の治療剤を含む、請求項33に記載の組成物。
- 前記追加の治療剤が、コルチコステロイド、細胞傷害性薬物、抗生物質、免疫抑制剤、非ステロイド系抗炎症薬、麻酔性鎮痛剤、局部麻酔剤、NMDAアンタゴニスト、神経弛緩剤、抗けいれん剤、鎮痙剤、制吐剤、抗うつ剤および筋肉弛緩剤からなる群から選択される、請求項34に記載の組成物。
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GB1010453.7 | 2010-06-22 | ||
GB1010453.7A GB2481407B (en) | 2010-06-22 | 2010-06-22 | A rapid onset liquid midazolam composition for buccal administration |
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EP (1) | EP2585038A1 (ja) |
JP (1) | JP4943550B2 (ja) |
AU (1) | AU2011268706B2 (ja) |
CA (1) | CA2803258C (ja) |
GB (1) | GB2481407B (ja) |
NZ (1) | NZ605656A (ja) |
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KR101964571B1 (ko) * | 2015-06-19 | 2019-04-02 | 해로우 헬스 인코포레이티드 | 마취용 약학 조성물 |
US10555952B2 (en) | 2015-06-19 | 2020-02-11 | Melt Pharmaceuticals, Inc. | Pharmaceutical compositions and methods for anesthesiological applications |
US10391102B2 (en) | 2015-06-19 | 2019-08-27 | Melt Pharmaceuticals, Inc. | Pharmaceutical compositions and methods for anesthesiological applications |
US10085971B2 (en) | 2016-08-22 | 2018-10-02 | Navinta Iii Inc | Pharmaceutical solution of asenapine for sublingual or buccal use |
CA3085223A1 (en) * | 2017-12-21 | 2019-06-27 | Pepsico, Inc. | Multi-ingredient ephemeral beverage pod for making a beverage |
CN109438583B (zh) * | 2018-11-26 | 2021-07-13 | 黑龙江八一农垦大学 | 一种顺序式模拟移动色谱纯化抗性糊精的方法 |
CA3130729A1 (en) * | 2019-02-22 | 2020-08-27 | Sun Pharmaceutical Industries Limited | Infusion bag of midazolam for intravenous use |
CN111410658B (zh) * | 2020-03-30 | 2021-03-26 | 江苏恩华药业股份有限公司 | 咪达唑仑或其药物组合物的杂质a和杂质b及其用途 |
CN113209013B (zh) * | 2021-06-24 | 2023-04-07 | 新疆特丰药业股份有限公司 | 一种咪达唑仑液体制剂及其制备方法和用途 |
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WO2001030391A2 (en) * | 1999-10-27 | 2001-05-03 | Farmarc Nederland Bv | Pharmaceutical composition containing midazolam |
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GB0130964D0 (en) | 2001-12-24 | 2002-02-13 | Special Products Ltd | Pharmaceutical composition |
GB0400804D0 (en) * | 2004-01-14 | 2004-02-18 | Innoscience Technology Bv | Pharmaceutical compositions |
TW200824693A (en) * | 2006-08-28 | 2008-06-16 | Jazz Pharmaceuticals Inc | Pharmaceutical compositions of clonazepam and methods of use thereof |
CN101678112B (zh) * | 2007-01-19 | 2016-08-31 | 哈南亚有限公司 | 用于递送治疗剂的方法和组合物 |
US20080275030A1 (en) * | 2007-01-19 | 2008-11-06 | Sveinbjorn Gizurarson | Methods and Compositions for the Delivery of a Therapeutic Agent |
US20090258865A1 (en) * | 2008-03-28 | 2009-10-15 | Hale Biopharma Ventures, Llc | Administration of benzodiazepine compositions |
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EP2585038A1 (en) | 2013-05-01 |
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US20120022051A1 (en) | 2012-01-26 |
WO2011161439A1 (en) | 2011-12-29 |
GB2481407B (en) | 2012-05-23 |
NZ605656A (en) | 2015-05-29 |
GB2481407A (en) | 2011-12-28 |
AU2011268706A1 (en) | 2013-01-31 |
TW201206934A (en) | 2012-02-16 |
AU2011268706B2 (en) | 2014-11-27 |
US8455478B2 (en) | 2013-06-04 |
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GB201010453D0 (en) | 2010-08-04 |
US20140094452A1 (en) | 2014-04-03 |
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