CN1326340A - 用于治疗急性疾病的药用组合物 - Google Patents
用于治疗急性疾病的药用组合物 Download PDFInfo
- Publication number
- CN1326340A CN1326340A CN99813545A CN99813545A CN1326340A CN 1326340 A CN1326340 A CN 1326340A CN 99813545 A CN99813545 A CN 99813545A CN 99813545 A CN99813545 A CN 99813545A CN 1326340 A CN1326340 A CN 1326340A
- Authority
- CN
- China
- Prior art keywords
- compositions
- mucus
- viscosifier
- biology
- cellulose
- 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
Links
Images
Classifications
-
- 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
- A61K9/0053—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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- 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
-
- 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
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
-
- 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
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/5415—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 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- 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
- A61K31/55—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
-
- 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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/84—Valerianaceae (Valerian family), e.g. valerian
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2242—Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Abstract
描述用于治疗急性疾病的药用组合物。所述组合物包含与生物增粘剂和/或粘液增粘剂结合的,以吸附于载体粒子表面的微粒形式存在的至少一种药用活性物质的基本上无水的有序混合物,载体基本上大于活性物质的粒子且可溶于水。本发明也涉及制备组合物的方法并涉及用于治疗急性疾病的组合物的用途。
Description
发明领域
本发明涉及迅速起效的用于舌下给予药物的药用组合物,涉及制备这样的组合物的方法,并涉及通过使用这样的组合物治疗急性疾病的方法。
发明背景
急性和/或严重疾病是紧急治疗或住院的常见原因。该类最普遍的疾病之一为急性或突发性疼痛。在癌症患者中,通常用非甾体抗炎药(NSAIDs)和阿片剂单独或联合治疗疼痛。通常给予需要阿片样物质的癌症疼痛患者缓慢释放的阿片剂(缓释的吗啡或凯托米酮或经皮给予芬太尼),癌症疼痛的特征为不充分的痛觉缺失阶段(突发性疼痛)。它们大多数情况下经常是由于患者增加的体力活动。然而,经给予增加时间的应急(contingent)剂量的长效镇痛药来治疗突发性疼痛可引起副作用例如过度镇静、恶心和便秘。
其它需要快速起效治疗的疾病和病症为例如肺水肿、胃食管返流、失眠和肾石病。
目前可口服、直肠或舌下给药的制剂具有相对长的起效时间或其不能良好适宜控制急性疾病的不稳定的吸收特性。
通常用阿片类镇痛药治疗急诊手术/术后或创伤/创伤后疼痛的症状以及由于严重疾病(例如心肌梗塞、肾石病等)引起的疼痛,所述镇痛药经非肠道(经静脉或肌内给药)给药以得到迅速起效的镇痛作用。在这样的情况中,迅速起效的口服选择具有值得考虑的治疗意义。对其它急性疾病的治疗,提供快速起效的治疗组合物(其可口服给药以替代非肠道或直肠给药)也具有重要意义。
然而,许多有利于口服给药的药用活性成分不适宜于吞服。例如,胃肠道体液可使它们失去活性,由于在水介质中的低的溶解度而具有缓慢的作用,或者对胃肠道的酶代谢机制是高度敏感的且具有不良的吸收性质,如对肽类激素举例说明的那样。因此,可优选安排活性成分通过口腔粘膜吸收。这里,给药最优选的途径是借助舌下途径。在这种给药中,把药用组合物的剂型放置于舌下,且活性成分经周围的粘膜吸收。然而,用这种给药方法,患者经吞服唾液来吞服药物的风险是人们所熟知的。
芬太尼,N-(1-苯乙基-4-哌啶基)-丙酰胺或它的药学上可接受的盐之一可用于治疗急性疼痛。该化合物为阿片样物质激动剂且具有阿片剂例如吗啡和哌替啶的许多药代动力学性质。然而,与这些阿片剂相比较,芬太尼呈现很小的催眠活性,极少诱导组胺释放,并且呼吸抑制存在时间更短。用于静脉、颊内(锭剂-跨膜)和经皮给药的芬太尼是市场上可得到的。
非肠道给予芬太尼之后,镇痛作用比吗啡和哌替啶更迅速,延长时间较短。静脉给药后的镇痛起效是迅速的。在几分钟内即达到峰镇痛。如同例如由Farrar等,J.Natl.Cancer Inst.,1998,90(8),第611-616页描述的那样,经锭剂跨颊膜给药后,通常在30分钟内完成锭剂的消耗且大约20分钟后出现峰血浆浓度。在5-15分钟内,镇痛作用明显并在大约20-50分钟时达峰。当对胃肠道摄取而言这是一个优于口服给药的改进时,镇痛作用快速起效对患者基本上是有益的。另外,患者吞服锭剂给予芬太尼的基本量。这是不合乎需要的且导致给予过量的药物,这可产生副作用。
发明目的
本发明的一个目的是提供经口服给予至少一种药用活性成分,以在给药后短时间内产生所述药物的药理有效血浆浓度水平的方式来治疗急性疾病。
本发明另一个目的是提供适合于这样目的的药用组合物。
本发明另一个目的是提供制备这样的组合物的方法。
本发明另外的目的是提供制备用于舌下给药的药物的方法,所述药物含有用于治疗急性疾病的、生理有效剂量的至少一种药用活性化合物。
绘图的描述
本发明的唯一绘图显示在本发明组合物中活性药物的生物利用度的试验结果。它是显示药物对给药后时间的血浆浓度的图。
发明概述
根据本发明,急性疾病的口服治疗包括舌下给予包含药理有效量的至少一种药用活性成分的有序混合物。舌下给予与生物粘附和/或粘液粘附促进化合物组合的所述药物。
本发明另外也提供单次剂量的用于舌下给药的药用组合物,组合物包含药理有效量的至少一种药用活性物质。所述组合物也包含促进生物粘附或粘液粘附的化合物。该组合物通过吞服唾液可减少不稳定的药物吸收且能使小量所述药物给药。因此,它基本上可减少副作用和患者之间以及患者之间治疗应答的变化的风险。因此降低药物蓄积的风险,使药用制剂很好适合于患有急性疾病的患者的重复给药。
包含在本发明药用组合物中的活性物质的量明显依多种因素而定,它们经治疗医师评价。在这样的因素当中,可被提到的有,所使用的具体药物和接受治疗疾病的类型、患者的医疗状态和其它的因素。
当芬太尼用于治疗急性或突发性疼痛时,本发明组合物应包含0.05多至20%(重量)的芬太尼或它的药学上可接受的盐之一。组合物更优选包含0.05至5%(重量)的芬太尼,并特别为0.1至1%(重量)。含量也能表达为芬太尼在组合物剂型例如片剂中的量。在这种情况中,剂量单位应包含0.05至20mg,并优选为0.1至5mg的芬太尼。当芬太尼以盐形式使用时,应该相应重新计算这些百分比和量。
另外根据本发明,舌下组合物包含用以精细颗粒形式存在的药用活性物质包衣的一种或多种生物粘附和/或粘液粘附的载体物质的混合物。
优选通过使用在欧洲专利EP 0 324 725中公开的用于配制迅速溶解有序混合物的组合物的技术配制本发明组合物。在这些组合物中,处于良好分散状态下的药物覆盖于基本上较大的载体粒子表面。这样的组合物在水中快速崩解,由此来分散它们的微观的药物粒子的内容物。
然而。迄今已报道使用迅速溶解药物的有序混合物的先有技术仅适宜用于常规口服药物治疗,即用于其打算吞服的固体剂型。对这样的制剂,药物粒子的溶解发生在胃中,即发生在存在相对大量的、能溶解药物粒子的液体的环境下。在整个先有的技术文献中,用大量的水,一般是1升,进行有序混合物的溶出试验。人们不认为使用舌下给药的有序混合物的可行性是易于操作的方法,其中可以作为溶剂的液体的体积被限定为几毫升。因此,人们不期待固体剂型制剂和给药途径的目前形式给出正面的和有用的结果。在这样的有序混合物中,活性成分或药物具有低于10μm的平均粒径。在重量基础上测定该粒径,如同本领域技术人员已知的那样,通过干法筛选分析直接得到。
另外将生物和/或粘液增粘剂加入到本发明的载体粒子中。生物和/或粘液增粘剂在使活性物质粘附于口腔粘膜中是有效的,且与水接触还可具有溶胀和伸展的性质,并因此当用唾液润湿时使片剂或载体粒子崩解。然后生物/粘液增粘剂必须存在于载体粒子的表面,但是如以下描述的那样,其也可任选存在于这些粒子中间。
短语“粘液粘附”意指粘附于由粘液覆盖的粘膜,例如那些口腔中的那些粘液,而短语“生物粘附”意指粘附于更广泛的生物表面,包括未由粘液覆盖的粘膜。这些短语一般作为定义有些重叠,且通常可互换使用,尽管短语“生物粘附”具有一些更广的范围。在本发明说明书和权利要求中,两种短语用于作为与本发明目标相同的目的,且这些短语通过使用常见的术语“生物/粘液粘附”来表达。
基于总组合物,适宜的载体粒子含有0.1至25%(重量)的生物/粘液粘附促进化合物。在实践中,已发现低于1%(重量)的含量产生不充分的生物/粘液粘附作用。生物/粘液增粘剂的含量的优选范围为1至15%(重量)。
优选所述生物/粘液增粘剂为聚合物物质,优选为具有平均分子量大于5,000(平均重量)的物质。在生物/粘液粘合力的产生中,粘液增粘剂界面的水合水平是重要的。因此,聚合物溶胀越快,生物/粘液粘附作用启动越快。生物粘附化合物的水合作用也使它们用作本发明的吸收增强剂。
所述载体粒径优选为50至750μm,且更优选为100至600μm。尽管能够使用所指明的范围以外的粒径,当从具有这样大小的粒子配制药用制剂时,发现实验特别困难。所使用的载体可包括药学上可接受的,在水中可高度溶解的,且能够配制成适宜于掺入生物/粘液增粘剂的粒子的任何物质。多种这样的物质对本领域技术人员是已知的。作为适宜的实例可提及的是碳水化合物、例如糖、甘露糖醇和乳糖、或药学上可接受的无机盐,例如氯化钠或磷酸钙。
与本发明一个特别优选方面相一致,载体也包括崩解促进剂。当它形成药用组合物的一部分与压制片剂时,崩解促进剂也意指其易于撞裂或粉碎的易碎物质。如果生物/粘液增粘剂也掺合在载体中以及加入到载体表面,然后生物/粘液增粘剂的另外的表面可暴露于水合作用。当生物/粘液增粘剂也用作崩解剂时,该作用是特别重要的。已发现甘露糖醇和乳糖特别适宜用作崩解促进剂。
把药学上可接受的表面活性剂加入到组合物中也是本发明的优选特征。表面活性剂的增加润湿作用增强载体粒子的水合作用,其导致生物/粘液粘附作用更快启动。表面活性剂应为良好分散的形式并与活性物质紧密混合。表面活性剂的量应为组合物的0.5至5%(重量),而且优选为0.5至3%(重量)。
作为适宜的表面活性剂的实例可提及的是十二烷基硫酸钠、多乙氧基醚、胆汁酸盐和它们的混合物。
多种本领域已知的聚合物能够用作生物/粘液增粘剂。除它们的聚合性质以外,它们的溶胀能力是重要的。另一方面,它们基本上不溶于水也是重要的。当与水或唾液发生接触时,它们对体积的溶胀因子应优选为至少10,其中至少是20的因子为更优选。这样的生物/粘液增粘剂的实例包括纤维素衍生物例如羟丙基甲基纤维素(HPMC)、羟乙基纤维素(HEC)、羟丙基纤维素(HPC)、甲基纤维素、乙基羟乙基纤维素、羧甲基纤维素和羧甲基纤维素钠(NaCMC)、淀粉衍生物例如中度交联淀粉、丙烯酸类聚合物例如卡波姆和它的衍生物(Polycarbophyl,Carbopol,等)、聚环氧乙烷(PEO)、脱乙酰壳多糖(多-(D-葡糖胺))、天然聚合物例如明胶、藻酸钠、果胶、黄原胶、瓜尔胶、聚-共-(甲基乙烯醚/马来酸酐)、小核菌葡聚糖(scleroglucan)、微晶纤维素(Avicel)和交联羧甲基纤维素。也能够使用两种或更多的生物/粘液聚合物的组合。更通常的讲,可将显示生物/粘液粘附特性的任何生理学上可接受的试剂成功用于掺入到载体中。例如,按照G.Sala等,Proceed.Int.Symp.Contr.Release.Bioact.Mat.16:420,1989的方法,能够体外测定生物/粘液粘附作用。
一些适宜的商业来源的代表性生物/粘液粘附聚合物包括:
Carbopol丙烯酸共聚物-BF Goodrich化学公司,Cleveland,08,USA;
HPMC-Dow化学公司,Midland,),MI,USA;
NEC(Natrosol)-Hercules公司,Wilmington,DE,USA;
HPC(Klucel)-Dow化学公司,Midland,MI,USA;
NaCMC-Hercules Inc.Wilmington,DE,USA;
PEO-Aldrich化学公司,USA;
藻酸钠-Edward Mandell公司,Carmel,NY,USAi
果胶-BF Goodrich化学公司,Cleveland,OH,USA;
Ac-Di-Sol(具有高溶胀性的改良纤维素胶)-FMC公司,USA;
Actigum,-Mero-Rousselot-Satia,Baupte,法国;
Satiaxane-Sanofi BioIndustries,巴黎,法国;
Gantrez-ISP,米兰,意大利;
脱乙酰壳多糖-Sigma,圣路易斯,MS,USA;
依所使用的生物/粘液增粘剂的类型和比例而定,生物/粘液粘附的比例和强度是可以变化的。按照本发明优选方面之一,具有高的和迅速溶胀能力的物质为优选。
为使本发明药用组合物正确地发挥作用,当向其中加入生物/粘液增粘剂时,该增粘剂必须定位于载体粒子的表面。然后以多种方法将生物/粘液增粘剂混合于载体粒子中。在本发明一个优选实施方案中,将细分的特定量的生物/粘液增粘剂与粗载体混合足够长的时间以产生有序混合物,在那里更细的粒子作为粘附于载体粒子表面的分散的基本粒子存在。因此,用与欧洲专利0,324,725号中描述的活性化合物那样相同的方法将生物/粘液增粘剂混合。
在本发明的另一个优选实施方案中,除了它在载体粒子表面上的外周趋向,生物/粘液增粘剂也可以多种方式掺入到载体中。例如,能够将细分散的载体与在液体中的细分散的生物/粘液增粘剂一起制粒,该液体不溶解生物/粘液增粘剂或引起它溶胀。在这种情况下,首先将干燥的成分混合,然后用非溶解性/非溶胀性液体例如绝对乙醇把生成的混合物润湿。将生成的物质制粒,例如通过滤膜压制它。之后干燥并很好研磨。或者,干燥润湿的物质,然后制粒。产生本发明载体粒子的另一种方法是通过把载体试剂溶解在不溶解生物/粘液增粘剂或引起它溶胀的溶剂中,随后把生物/粘液增粘剂加入到溶液中,蒸发溶剂,并把残余物制粒。其它的方法对本领域技术人员也是可以接受的。不考虑使用的方法,在最后阶段中,制备适宜的粒积部分的含有生物/粘液增粘剂的载体物质,例如,通过使粒子混合物通过筛选或适当筛目的筛子,例如35至170目的U.S.筛目。
生物/粘液增粘剂适宜具有1至100μm的粒径。当打算将该增粘剂的粒子与载体粒子混合以形成有序混合物时,它们的体积处于较低的粒子间隔部分之间,且那么它们的粒径适宜低于10μm。当打算将生物/粘液增粘剂掺入到载体粒子中时,它的粒径可处于粒子大小间隔的上限部分内。
本发明尤其涉及给予用于治疗要求迅速和短暂作用的医学病症例如疼痛、失眠、变应性疾病和肺水肿的药物。这样的药物的非限制性实例可提及的有吗啡(镇痛药)、芬太尼(镇痛药)、阿芬太尼(镇痛药)、舒芬太尼(镇痛药)、丁丙诺啡(镇痛药)、苯噻啶(镇痛药)、舒马曲坦(镇痛药)、吲哚美辛(镇痛药)、舒林酸(镇痛药)、双氯芬酸(镇痛药)、酮咯酸(镇痛药)、吡罗昔康(镇痛药)、替诺昔康(镇痛药)、布洛芬(镇痛药)、萘普生(镇痛药)、酮洛芬(镇痛药)、布他唑立丁(镇痛药)、保泰松(镇痛药)、地西泮(催眠药)、奥沙西泮(催眠药)、佐匹克隆(催眠药)、唑吡坦(催眠药)、丙酰异丙嗪(催眠药)、valeriana(催眠药)、甲氧异丁嗪(催眠药)、赛克利嗪(抗过敏药)、西替利嗪(抗过敏药)、特非那定(抗过敏药)、阿伐斯汀(抗过敏药)、fexofenadine(抗过敏药)和呋塞米(利尿药)。
其它的药物可从增加的吸收中受益且其可用于治疗要求迅速作用的医学症状包括(未含任何限制性意义)多种肽类和酶类,例如心钠尿肽(ANP、ANF、auriculin)(利尿药)、脑钠尿肽(利尿药)、血小板聚集抑制剂(抗凝药)、链激酶(抗凝药)、肝素(抗凝药)、尿激酶(抗凝药)、肾素抑制剂(抗高血压药)、胰岛素(抗糖尿病药)和包括肽类的睡眠药(催眠药)。
必须避免暴露于胃酸的并且借助本发明制剂的生物/粘液粘附性质能够把吞服含有活性药物的唾液减小至最低程度的药物其它的实例包括(不含有任何限制意义),用作H+、K+和ATP酶抑制剂(减少胃酸)苯并咪唑衍生物,例如奥美拉唑、泮妥拉唑、雷贝拉唑和兰索拉唑。其它的H+、K+和ATP酶抑制剂包括烯丙基异硫代氰酸酯、trifluorperazide、诺利溴铵、RP 40749和苯辛替明。
本发明尤其适宜于给予芬太尼和它的药学上可接受的盐类如不易于溶于水的枸橼酸盐或马来酸盐。芬太尼或它们的盐的粒子将适当具有大约24μm的最大粒径,但是将优选不大于大约10μm。在足够长的时间内,通过干法混合成分,使芬太尼粘附到载体粒子上。根据所使用的混合设备,这个时间能够变化。通过使用粒子混合设备,经对给出的活性成分的组合、生物/粘液增粘剂和载体的适宜的混合时间进行试验,本领域技术人员将毫无困难地进行测定。
本发明另一个优选方面包括在本发明组合物中掺入崩解剂。这样的崩解剂将加速载体粒子的分散。本发明崩解剂的实例包括交联聚乙烯吡咯烷酮、羧基甲基淀粉、天然淀粉、微晶纤维素、纤维素胶和这些物质的混合物。崩解剂优选含量为组合物的1%至10%。如所能观察到的那样,崩解剂和生物粘附/粘液增粘剂的定义有些部分一致,优选相同的物质具有两种功能。然而,注意到这两类赋形剂不等价是重要的,且存在不具有生物/粘液粘附性质的充分功能的崩解剂,反之亦然。
本发明中制备的有序混合物能掺入到多种打算舌下给药的药用制剂中。不考虑给予所述制剂的形式,制剂基本上不含有水是重要的,因为当与水或唾液接触时,它的生物/粘液增粘特性是由其实际上瞬间水合产生的。过早水合将大大减少粘液粘附促进性质并导致活性成分过早溶出。
通过使先前述及的有序混合物与在舌下制剂领域中使用的常规药用添加剂和赋形剂混合,能够得到优选用于舌下给药途径的药用组合物。适当的制剂方法对本领域技术人员是熟知的;参见例如,药用剂型:片剂第1卷,第2版,Lieberman等编辑,Marcel Dekker,纽约和巴塞尔,1989,第354-356页和在此引用的文献。适宜的添加剂包括另外的载体物质、防腐剂、润滑剂、助流剂、崩解剂、矫味剂和着色剂。
因此,本发明提供易于和低成本制备的,使活性成分迅速释放的,促进活性物质经口腔粘膜迅速摄取的,并增强其它不良溶解性物质例如肽类的摄取的剂型。低剂量活性物质的使用提供用于对需要治疗复发的急性疾病的患者实施重复给药方案时,维持短的作用持续时间。
通过参照显示优选的但不限制实施方案的实施例将更详细阐明本发明。实施例1.具有生物/粘液增粘性质的迅速崩解片剂的制备
从以下成份生产一批1000片片剂:将81.5g甘露糖醇和2.0g的Ac-Di-Sol(崩解剂和生物/粘液增粘剂)与大约170ml绝对乙醇混合。将干燥的混合物加压通过1mm筛目宽的金属筛,并将具有大约250至450微米粒径的生成部分与500mg微粉化的芬太尼和1.0g良好研磨的十二烷基硫酸钠(表面活性剂)混合50小时。把生成的混合物与5.0g的AvicelPh 101和10.0g藻酸钠(生物/粘液增粘剂和崩解剂)混合60分钟。在200MPa的紧密压力下,将生成的混合物压制成片剂,每片具有100mg重量并含有0.5mg芬太尼。
按照USP XXIII(paddle方法),在25和100rpm两种不同的搅拌速度下,研究由此产生的片剂的溶出速率实施例2.具有生物/粘液增粘性质的迅速崩解片剂的制备
从以下组合物生产一批1000片片剂:在V形混合器中,将91.0g甘露糖醇(250至450μm粒径的颗粒质量)和1.0g十二烷基硫酸钠和500mg微粉化的芬太尼混合24小时。然后,将5.0g的AvicelPh101和2.0g的Ac-Di-Sol(在此两者用作崩解剂和生物/粘液增粘剂)另外混合2小时。最后,把0.5g硬脂酸镁混合2分钟。在130MPa的紧密压力下,将生成的片剂块状物压制成片剂,每片含有0.5mg芬太尼。
使用在欧洲药典(最新版)中描述的装置,试验崩解时间。
发现崩解时间小于15秒。
为比较,也生产常规速溶片剂。将具有250-450微米粒径的干燥甘露糖醇与不含有任何另外的赋形剂的微粉化芬太尼干燥混合。混合时间为50小时。在200MPa的紧密压力下,将生成的混合物压制成片剂,每片含有0.5mg芬太尼。
来自该研究的结果显示具有本发明生物/粘液粘附性质的有序混合物(实施例1)具有与常规速溶片制剂相同的溶出速率。全部片剂在2分钟内溶解。此外,发现实施例2的片剂的迅速崩解与常规片剂相同或比后者更好。实施例3.舌下给药摄取的评价
向患有由于癌症的突发性疼痛的患者给予作为如在实施例1中所述配制的舌下片剂的400μg芬太尼。给药后,监测芬太尼的血浆浓度240分钟,并将结果显示在所附图中。将看到芬太尼的摄取是迅速的,5分钟后即达到最大值。这显示本发明的舌下制剂给出活性物质的迅速摄取,即使很小体积的液体就可以在该给药途径中溶出。实施例4.生物/粘液粘附性质的评价
为体外评价本发明制剂的生物/粘液粘附性质,使用允许直接在已完成的剂型(Sala,G.E.等,Proceed.Int.Symp.Contr.Release.Bioact.Mat.16:420,1989)上评价生物/粘液增粘性质的方法。评价基于测定需要从兔子肠粘膜除去活性物质所需要的水流。在37℃下,将一条兔子粘膜水平放置于适宜的温度控制室装置中。首先借助蠕动泵用预先测定体积的水洗涤该组织。然后将预先压制的实施例1组合物(5-15mg)放置于组织上并使之在那里保留2分钟以确保适宜的溶出。随后在10分钟内通过蠕动泵用水洗脱。收集冲洗出来的芬太尼,并为确立移出的芬太尼的百分比经放射免疫试验(RIA)测定它的量。随后使用增加洗脱流速,进行随后的试验。结果显示在表2中。对以下物质列出高流速下的除去百分比:
A本发明生物/粘液粘附混合物(实施例1);
B本发明生物/粘液粘附混合物(实施例2);
C不含有生物/粘液增粘剂的迅速溶出的常规混合物。
表2:
流速 所除去芬太尼的%
(ml/min)
A B C
>15 <50 <50 >95实施例5.用于给予呋塞米的迅速崩解片剂的制备
按照实施例1,制备用于舌下给药的具有生物/粘液粘附性质的迅速崩解片剂,每片含有20 mg呋塞米。与常规口服制剂相比较,所述片剂显示呋塞米的迅速释放并通过口腔粘膜促进吸收呋塞米。该制剂可用于治疗肺水肿。实施例6.用于给予心钠尿肽(ANP)的迅速崩解片剂的制备
按照实施例1,制备用于舌下给药的具有另外增强大分子的吸收的生物/粘液粘附性质的迅速崩解片剂,每片含有0.7mg的ANP。与常规口服制剂相比较,所述片剂显示ANP的迅速释放并通过口腔粘膜促进吸收ANP。该制剂可用于治疗肺水肿。实施例7.用于给予奥美拉唑的迅速崩解片剂的制备
按照实施例1,制备用于舌下给药的具有生物/粘液粘附性质的迅速崩解片剂,每片含有10mg奥美拉唑。与常规口服制剂相比较,所述片剂显示迅速释放的奥美拉唑并通过口腔粘膜促进吸收奥美拉唑,以及减少吞服唾液中的奥美拉唑。该制剂可用于治疗胃食管返流。实施例8.用于给予双氯芬酸的迅速崩解片剂的制备
按照实施例1,制备用于舌下给药的具有生物/粘液粘附性质的迅速崩解片剂,每片含有50mg双氯芬酸。与常规口服制剂相比较,所述片剂显示迅速释放的双氯芬酸并通过口腔粘膜促进吸收双氯芬酸。该制剂可用于治疗疼痛性疾病如肾石病(neprolithiasis)。
在先前的说明书中,参照多个实施例和优选实施方案,已描述本发明。然而,对本领域技术人员而言,很清楚本发明的范围不局限于这些实施例和实施方案,并且进一步的改进和变化是可能的而不背离本发明的思路。因此,仅由所附的权利要求限制本发明的范围。
权利要求书
按照条约第19条的修改
1. 经舌下给药用于治疗急性疾病的药用组合物,它包含基本无水、粘附于载体粒子表面的至少一种药用活性物质微粒和主要粘附于载体粒子表面的生物增粘剂和/或粘液增粘剂的有序混合物,所述粒子基本上大于所述微粒且可溶于水。
2. 权利要求1的组合物,其中所述一种或多种活性物质的微粒具有基于小于10μm的平均直径的重量。
3. 权利要求1或2的组合物,其中所述载体粒子的平均筛分直径小于750μm,优选为100至600μm。
4. 权利要求1-4的任何一项的组合物,其中所述载体粒子含有当压制时易于破碎的脆性物质。
5. 权利要求1-4的任何一项的组合物,其中所述载体粒子含有基于总组合物的0.1至25%(重量),优选为1至13%(重量)的生物/粘液增粘剂。
6. 权利要求5的组合物,其中所述生物/粘液增粘剂选自丙烯酸类聚合物、纤维素衍生物、具有生物/粘液粘附性质的天然聚合物,和它们的混合物。
7. 权利要求6的组合物,其中所述生物/粘液增粘剂选自纤维素衍生物并包括羟丙基甲基纤维素、羟乙基纤维素、羟丙基纤维素、羧甲基纤维素钠、甲基纤维素、乙基羟基乙基纤维素、羧甲基纤维素、微晶纤维素和改性纤维素胶、交联羧甲基纤维素、改性淀粉、丙烯酸聚合物包括卡波姆(carbomer)和它的衍生物、聚环氧乙烷、脱乙酰壳多糖、明胶、藻酸钠、果胶、小核菌葡聚糖(scleroglucan)、黄原胶、瓜尔胶、聚-共-(甲基乙烯醚/马来酸酐)和它们的混合物。
8. 权利要求1-7的任何一项的组合物,它还包含以细分散形式存在并与一种或多种活性物质紧密混合的药学上可接受的表面活性剂。
9. 权利要求8的组合物,其中所述表面活性剂以组合物的0.5至5%(重量),优选0.5至3%(重量)的量存在。
10. 权利要求8或9的组合物,其中所述表面活性剂选自十二烷基硫酸钠、多乙氧基醚、胆汁酸盐和它们的混合物。
11. 权利要求1-10的任何一项的组合物,其中所述载体粒子包含水溶性的、药学上可接受的碳水化合物和/或无机盐。
12. 权利要求11的组合物,其中所述载体粒子包含至少一种材料如甘露糖醇、乳糖、磷酸钙和糖。
13. 权利要求1-12的任何一项的组合物,其中所述载体粒子包含至少一种促进活性物质的微粒在舌下粘膜上分散的药用崩解剂。
14. 权利要求13的组合物,其中所述崩解剂选自交联聚乙烯吡咯烷酮、羧甲基淀粉、天然淀粉、微晶纤维素、纤维素胶和它们的混合物。
15. 权利要求13或14的组合物,其中所述崩解剂以组合物的1至10%(重量)的量存在。
16. 权利要求1-15的任何一项的组合物,其中所述药用活性物质为芬太尼或它的药学上可接受的盐。
17. 权利要求1-16的任何一项的组合物,用于经舌下给药治疗急性疾病。
18. 权利要求16的组合物,用于通过舌下给予芬太尼或它的药学上可接受的盐治疗急性或突发性疼痛。
19. 治疗急性疾病的方法,其中向受所述疾病困扰的个体舌下给予至少一个剂量单位的必须无水的药用组合物,该组合物包含有效量的至少一种以吸附于载体粒子表面的微粒形式存在的药用活性物质和生物增粘剂和/或粘液增粘剂,药用活性物质基本上大于所述微粒且基本是可溶于水的。
20. 权利要求19的方法,其中药用活性物质为芬太尼或它的药学上可接受的盐。
21. 权利要求20的方法,其中以每剂量单位0.05至20mg,优选0.1至5mg的量给予芬太尼。
Claims (21)
1. 经舌下给药用于治疗急性疾病的药用组合物,它包含基本无水、粘附于载体粒子表面的至少一种药用活性物质微粒和生物增粘剂和/或粘液增粘剂的有序混合物,所述粒子基本上大于所述微粒且可溶于水。
2. 权利要求1的组合物,其中所述一种或多种活性物质的微粒具有基于小于10μm的平均直径的重量。
3. 权利要求1或2的组合物,其中所述载体粒子的平均筛分直径小于750μm,优选为100至600μm。
4. 权利要求1-4的任何一项的组合物,其中所述载体粒子含有当压制时易于破碎的脆性物质。
5. 权利要求1-4的任何一项的组合物,其中所述载体粒子含有基于总组合物的0.1至25%(重量),优选为1至13%(重量)的生物/粘液增粘剂。
6. 权利要求5的组合物,其中所述生物/粘液增粘剂选自丙烯酸类聚合物、纤维素衍生物、具有生物/粘液粘附性质的天然聚合物,和它们的混合物。
7. 权利要求6的组合物,其中所述生物/粘液增粘剂选自纤维素衍生物并包括羟丙基甲基纤维素、羟乙基纤维素、羟丙基纤维素、羧甲基纤维素钠、甲基纤维素、乙基羟基乙基纤维素、羧甲基纤维素、微晶纤维素和改性纤维素胶、交联羧甲基纤维素、改性淀粉、丙烯酸聚合物包括卡波姆(carbomer)和它的衍生物、聚环氧乙烷、脱乙酰壳多糖、明胶、藻酸钠、果胶、小核菌葡聚糖(scleroglucan)、黄原胶、瓜尔胶、聚-共-(甲基乙烯醚/马来酸酐)和它们的混合物。
8. 权利要求1-7的任何一项的组合物,它还包含以细分散形式存在并与一种或多种活性物质紧密混合的药学上可接受的表面活性剂。
9. 权利要求8的组合物,其中所述表面活性剂以组合物的0.5至5%(重量),优选0.5至3%(重量)的量存在。
10. 权利要求8或9的组合物,其中所述表面活性剂选自十二烷基硫酸钠、多乙氧基醚、胆汁酸盐和它们的混合物。
11. 权利要求1-10的任何一项的组合物,其中所述载体粒子包含水溶性的、药学上可接受的碳水化合物和/或无机盐。
12. 权利要求11的组合物,其中所述载体粒子包含至少一种材料如甘露糖醇、乳糖、磷酸钙和糖。
13. 权利要求1-12的任何一项的组合物,其中所述载体粒子包含至少一种促进活性物质的微粒在舌下粘膜上分散的药用崩解剂。
14. 权利要求13的组合物,其中所述崩解剂选自交联聚乙烯吡咯烷酮、羧甲基淀粉、天然淀粉、微晶纤维素、纤维素胶和它们的混合物。
15. 权利要求13或14的组合物,其中所述崩解剂以组合物的1至10%(重量)的量存在。
16. 权利要求1-15的任何一项的组合物,其中所述药用活性物质为芬太尼或它的药学上可接受的盐。
17. 权利要求1-16的任何一项的组合物,用于经舌下给药治疗急性疾病。
18. 权利要求16的组合物,用于通过舌下给予芬太尼或它的药学上可接受的盐治疗急性或突发性疼痛。
19. 治疗急性疾病的方法,其中向受所述疾病困扰的个体舌下给予至少一个剂量单位的必须无水的药用组合物,该组合物包含有效量的至少一种以吸附于载体粒子表面的微粒形式存在的药用活性物质和生物增粘剂和/或粘液增粘剂,药用活性物质基本上大于所述微粒且基本是可溶于水的。
20. 权利要求19的方法,其中药用活性物质为芬太尼或它的药学上可接受的盐。
21. 权利要求20的方法,其中以每剂量单位0.05至20mg,优选0.1至5mg的量给予芬太尼。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE98032402 | 1998-09-24 | ||
SE9803240A SE9803240D0 (sv) | 1998-09-24 | 1998-09-24 | A pharmaceutical composition having a rapid action |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1326340A true CN1326340A (zh) | 2001-12-12 |
CN1173694C CN1173694C (zh) | 2004-11-03 |
Family
ID=20412702
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998135453A Expired - Lifetime CN1173694C (zh) | 1998-09-24 | 1999-09-24 | 用于治疗急性疾病的药用组合物 |
Country Status (30)
Country | Link |
---|---|
US (8) | US6761910B1 (zh) |
EP (5) | EP2805716B1 (zh) |
JP (1) | JP3381220B2 (zh) |
KR (1) | KR100760536B1 (zh) |
CN (1) | CN1173694C (zh) |
AT (1) | ATE365540T1 (zh) |
AU (1) | AU764346B2 (zh) |
BG (1) | BG65502B1 (zh) |
BR (1) | BRPI9913945B8 (zh) |
CA (3) | CA2345121C (zh) |
CY (5) | CY1107711T1 (zh) |
CZ (2) | CZ302975B6 (zh) |
DE (1) | DE69936393T2 (zh) |
DK (5) | DK2236132T3 (zh) |
EE (3) | EE05555B1 (zh) |
ES (5) | ES2507579T3 (zh) |
HK (4) | HK1091722A1 (zh) |
HU (2) | HU230342B1 (zh) |
IL (1) | IL142135A0 (zh) |
LU (1) | LU92636I2 (zh) |
MX (1) | MXPA01003068A (zh) |
NO (1) | NO332226B1 (zh) |
NZ (1) | NZ510284A (zh) |
PL (2) | PL204264B1 (zh) |
PT (5) | PT2805716T (zh) |
RU (1) | RU2193879C1 (zh) |
SE (1) | SE9803240D0 (zh) |
SK (1) | SK283302B6 (zh) |
TR (1) | TR200100855T2 (zh) |
WO (1) | WO2000016750A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102582106A (zh) * | 2006-05-23 | 2012-07-18 | 奥拉黑尔斯公司 | 具有阿拉伯树胶粘合剂的双层口用粘附性片剂 |
CN107157994A (zh) * | 2017-06-09 | 2017-09-15 | 董鹏 | 一种托拉塞米的舌下口服制剂 |
Families Citing this family (98)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6974590B2 (en) | 1998-03-27 | 2005-12-13 | Cima Labs Inc. | Sublingual buccal effervescent |
US20030091629A1 (en) * | 1998-03-27 | 2003-05-15 | Cima Labs Inc. | Sublingual buccal effervescent |
US20030118645A1 (en) * | 1998-04-29 | 2003-06-26 | Pather S. Indiran | Pharmaceutical compositions for rectal and vaginal administration |
SE9803239D0 (sv) * | 1998-09-24 | 1998-09-24 | Diabact Ab | Composition for the treatment of acute pain |
SE9803240D0 (sv) | 1998-09-24 | 1998-09-24 | Diabact Ab | A pharmaceutical composition having a rapid action |
ES2302742T5 (es) | 2000-07-31 | 2011-10-10 | Nycomed Danmark Aps | Pulverizador nasal para suministrar una composición farmacéutica. |
KR20030072555A (ko) * | 2000-12-07 | 2003-09-15 | 알타나 파마 아게 | 산 불안정성 활성 성분을 포함하는 신속 붕해 정제 |
US20020106407A1 (en) * | 2000-12-11 | 2002-08-08 | Dennis Coleman | Method and apparatus for treating breakthrough pain |
JP4850346B2 (ja) * | 2001-03-15 | 2012-01-11 | 救急薬品工業株式会社 | 粘膜貼付剤 |
DE10141650C1 (de) | 2001-08-24 | 2002-11-28 | Lohmann Therapie Syst Lts | Transdermales Therapeutisches System mit Fentanyl bzw. verwandten Substanzen |
US20030165566A1 (en) * | 2002-01-10 | 2003-09-04 | O'toole Edel | Sedative non-benzodiazepine formulations |
JP2005521662A (ja) * | 2002-01-25 | 2005-07-21 | サンタラス インコーポレイティッド | プロトンポンプ阻害剤の経粘膜送達 |
DK1487416T3 (da) | 2002-03-26 | 2010-03-29 | Teva Pharma | Lægemiddelmikropartikler |
ES2199061B1 (es) * | 2002-06-10 | 2005-02-16 | Laboratorios Vita, S.A. | Comprimidos bucodispersables y procedimiento para su obtencion. |
GB0217056D0 (en) * | 2002-07-23 | 2002-08-28 | Ass Octel | Use |
EP2218448B1 (en) | 2002-12-13 | 2015-09-23 | Durect Corporation | Oral drug delivery system comprising high viscosity liquid carrier materials |
GB0300531D0 (en) | 2003-01-10 | 2003-02-12 | West Pharm Serv Drug Res Ltd | Pharmaceutical compositions |
KR20050096950A (ko) * | 2003-01-31 | 2005-10-06 | 오렉쏘 에이비 | 신속-작용 약학 조성물 |
ITRM20030288A1 (it) * | 2003-06-10 | 2004-12-11 | Valerio Cioli | Somministrazione sublinguale di antinfiammatori non steroidei (fans) |
WO2005039640A1 (en) * | 2003-10-03 | 2005-05-06 | Allergan Inc. | Compositions comprising trefoil factor family peptides and/or mucoadhesives and proton pump inhibitor prodrugs |
US7201920B2 (en) | 2003-11-26 | 2007-04-10 | Acura Pharmaceuticals, Inc. | Methods and compositions for deterring abuse of opioid containing dosage forms |
ME01300B (me) * | 2003-12-31 | 2013-12-20 | Cima Labs Inc | Uglavnom linearne efervescentne oralne dozne forme fentanila i metode davanja |
US7858121B2 (en) * | 2003-12-31 | 2010-12-28 | Cima Labs, Inc. | Effervescent oral fentanyl dosage form and methods of administering fentanyl |
JP5244318B2 (ja) | 2003-12-31 | 2013-07-24 | シーマ・ラブス、インコーポレイテッド | 発泡性経口アヘン薬投薬形態およびアヘン薬の投与方法 |
KR20130116378A (ko) * | 2004-02-17 | 2013-10-23 | 트랜스셉트 파마슈티칼스, 인코포레이티드 | 구강 점막을 가로지르는 수면제 전달용 조성물 및 이의 사용 방법 |
US8163114B2 (en) * | 2004-04-07 | 2012-04-24 | New Jersey Institute Of Technology | Netshape manufacturing processes and compositions |
US7754230B2 (en) * | 2004-05-19 | 2010-07-13 | The Regents Of The University Of California | Methods and related compositions for reduction of fat |
MXPA06013437A (es) * | 2004-05-19 | 2007-03-23 | Los Angeles Biomed Res Inst | Uso de un detergente para la eliminacion no quirurgica de grasa. |
US20060127468A1 (en) * | 2004-05-19 | 2006-06-15 | Kolodney Michael S | Methods and related compositions for reduction of fat and skin tightening |
GB0423800D0 (en) | 2004-10-27 | 2004-12-01 | Orexo Ab | New pharmaceutical formulations |
JP5112882B2 (ja) * | 2005-01-14 | 2013-01-09 | シーマ・ラブス、インコーポレイテッド | 曲げてから剥がす錠剤パッケージ |
MX2007008575A (es) * | 2005-01-14 | 2007-09-07 | Cima Labs Inc | Empaque vesicular resistente a ninos, no rasgable. |
CN101132769A (zh) * | 2005-02-10 | 2008-02-27 | 奥瑞克索股份公司 | 用于药物的跨黏膜给药的药物组合物 |
FR2883179B1 (fr) | 2005-03-18 | 2009-04-17 | Ethypharm Sa | Comprime enrobe |
US20090232898A1 (en) * | 2005-03-28 | 2009-09-17 | Anders Pettersson | Pharmaceutical Compositions Useful in the Treatment of Migraine |
CA2599384A1 (en) * | 2005-03-28 | 2006-10-05 | Orexo Ab | New pharmaceutical compositions useful in the treatment of parkinson's disease |
MX2007011977A (es) * | 2005-03-28 | 2007-12-07 | Orexo Ab | Composiciones farmaceuticas novedosas utiles en el tratamiento del dolor. |
ZA200710205B (en) * | 2005-05-25 | 2009-03-25 | Transcept Pharmaceuticals Inc | Solid compositions and methods for treating middle-of-the night insomnia |
JP2008542299A (ja) * | 2005-05-25 | 2008-11-27 | トランセプト・ファーマシューティカルズ・インコーポレイテッド | 真夜中不眠症の治療のための固体組成物およびその治療方法 |
US20070225322A1 (en) * | 2005-05-25 | 2007-09-27 | Transoral Pharmaceuticals, Inc. | Compositions and methods for treating middle-of-the night insomnia |
US20070287740A1 (en) * | 2005-05-25 | 2007-12-13 | Transcept Pharmaceuticals, Inc. | Compositions and methods of treating middle-of-the night insomnia |
US20070104763A1 (en) * | 2005-11-10 | 2007-05-10 | Navinta Llc | Composition of fentanyl citrate oral solid transmucosal dosage form, excipient and binding material therefore, and methods of making |
US8357114B2 (en) | 2006-01-06 | 2013-01-22 | Acelrx Pharmaceuticals, Inc. | Drug dispensing device with flexible push rod |
US8252328B2 (en) * | 2006-01-06 | 2012-08-28 | Acelrx Pharmaceuticals, Inc. | Bioadhesive drug formulations for oral transmucosal delivery |
US9289583B2 (en) | 2006-01-06 | 2016-03-22 | Acelrx Pharmaceuticals, Inc. | Methods for administering small volume oral transmucosal dosage forms using a dispensing device |
US8753308B2 (en) | 2006-01-06 | 2014-06-17 | Acelrx Pharmaceuticals, Inc. | Methods for administering small volume oral transmucosal dosage forms using a dispensing device |
US8865743B2 (en) | 2006-01-06 | 2014-10-21 | Acelrx Pharmaceuticals, Inc. | Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain |
US8535714B2 (en) | 2006-01-06 | 2013-09-17 | Acelrx Pharmaceuticals, Inc. | Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain |
US8252329B2 (en) | 2007-01-05 | 2012-08-28 | Acelrx Pharmaceuticals, Inc. | Bioadhesive drug formulations for oral transmucosal delivery |
US9066847B2 (en) | 2007-01-05 | 2015-06-30 | Aceirx Pharmaceuticals, Inc. | Storage and dispensing devices for administration of oral transmucosal dosage forms |
US8202535B2 (en) | 2006-01-06 | 2012-06-19 | Acelrx Pharmaceuticals, Inc. | Small-volume oral transmucosal dosage forms |
MX2008009522A (es) * | 2006-01-25 | 2009-01-07 | Insys Therapeutics Inc | Rocio de fentanilo sublingual. |
MX2008012794A (es) * | 2006-04-03 | 2008-10-15 | Teva Pharma | Microparticulas de farmacos. |
US20070260491A1 (en) * | 2006-05-08 | 2007-11-08 | Pamela Palmer | System for delivery and monitoring of administration of controlled substances |
US20070286900A1 (en) * | 2006-06-09 | 2007-12-13 | Catherine Herry | Low dose tablets of opioid analgesics and preparation process |
ITMI20061117A1 (it) * | 2006-06-09 | 2007-12-10 | Michele Bonanomi | Una composizione farmaceutica per la somministrazione sublinguale di vaccini metodo per la sua preparazione e sui usi |
US20070299687A1 (en) * | 2006-06-23 | 2007-12-27 | Pamela Palmer | Inpatient system for patient-controlled delivery of oral transmucosal medications dosed as needed |
TW200824693A (en) | 2006-08-28 | 2008-06-16 | Jazz Pharmaceuticals Inc | Pharmaceutical compositions of clonazepam and methods of use thereof |
EP1897543A1 (en) | 2006-08-30 | 2008-03-12 | Euro-Celtique S.A. | Buprenorphine- wafer for drug substitution therapy |
JP5484062B2 (ja) | 2006-12-04 | 2014-05-07 | オレクソ・アクチエボラゲット | オピオイドを含む新規の非−乱用性医薬組成物 |
WO2008070795A2 (en) * | 2006-12-06 | 2008-06-12 | Somaxon Pharmaceuticals, Inc. | Combination therapy using low-dose doxepin for the improvement of sleep |
CA2673481A1 (en) | 2006-12-19 | 2008-06-26 | University Of Virginia Patent Foundation | Combined effects of topiramate and ondansetron on alcohol consumption |
DE102007010109A1 (de) * | 2007-02-28 | 2008-09-04 | Henkel Ag & Co. Kgaa | Wirkstoffträgersysteme |
CA2959274C (en) * | 2007-12-06 | 2019-07-09 | Pain Therapeutics, Inc. | Micronized opioid compositions, formulations and dosage forms and methods of making same |
JP2011506319A (ja) | 2007-12-06 | 2011-03-03 | デュレクト コーポレーション | 疼痛、関節炎症状、または慢性疾患に伴う炎症の治療に有用な方法 |
EP2254558B1 (en) * | 2008-02-05 | 2019-03-13 | Alpex Pharma SA | Orally disintegrating tablets with speckled appearance |
US20090263476A1 (en) * | 2008-04-16 | 2009-10-22 | Jobdevairakkam Christopher N | Composition of Rapid Disintegrating Direct Compression Buccal Tablet |
EP2111857A1 (de) * | 2008-04-25 | 2009-10-28 | Acino AG | Transdermales therapeutisches System zur Verabreichung von Fentanyl oder einem Analogstoff hiervon |
US20100260844A1 (en) | 2008-11-03 | 2010-10-14 | Scicinski Jan J | Oral pharmaceutical dosage forms |
US8945592B2 (en) | 2008-11-21 | 2015-02-03 | Acelrx Pharmaceuticals, Inc. | Sufentanil solid dosage forms comprising oxygen scavengers and methods of using the same |
SE533540C2 (sv) | 2008-12-19 | 2010-10-19 | Neoinvent Medical Engineering Ab | Administrerinssystem för administrering av en substans i munhålan |
US8101593B2 (en) | 2009-03-03 | 2012-01-24 | Kythera Biopharmaceuticals, Inc. | Formulations of deoxycholic acid and salts thereof |
JP5702526B2 (ja) | 2009-04-30 | 2015-04-15 | Esファイバービジョンズ株式会社 | 抗ウイルス性を有する硫酸化セルロースを担持させた繊維集合体 |
CA2775890C (en) | 2009-09-30 | 2016-06-21 | Acura Pharmaceuticals, Inc. | Methods and compositions for deterring abuse |
NO2493457T3 (zh) | 2009-10-30 | 2018-01-06 | ||
EP2519229A2 (en) | 2009-12-29 | 2012-11-07 | Novartis AG | New pharmaceutical dosage form for the treatment of gastric acid-related disorders |
WO2011080502A2 (en) | 2009-12-29 | 2011-07-07 | Orexo Ab | New pharmaceutical dosage form for the treatment of gastric acid-related disorders |
IL278149B2 (en) | 2010-07-02 | 2024-03-01 | Univ Virginia Patent Foundation | A molecular genetic approach to the treatment and diagnosis of alcohol and drug dependence |
ITMI20101426A1 (it) * | 2010-07-29 | 2012-01-30 | Altergon Sa | Composizione contenente condroitin solfato |
FR2967066B1 (fr) * | 2010-11-04 | 2013-06-14 | Ethypharm Sa | Utilisation par voie sublinguale de microgranules non comprimes |
US8722636B2 (en) * | 2011-01-31 | 2014-05-13 | New Market Pharmaceuticals, LLC | Animal treatments |
CA2827643C (en) | 2011-02-18 | 2019-05-07 | Kythera Biopharmaceuticals, Inc. | Treatment of submental fat |
US8653058B2 (en) | 2011-04-05 | 2014-02-18 | Kythera Biopharmaceuticals, Inc. | Compositions comprising deoxycholic acid and salts thereof suitable for use in treating fat deposits |
EP2707020A4 (en) | 2011-05-09 | 2015-01-14 | Univ Virginia Patent Found | COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER |
CA2848211A1 (en) | 2011-09-09 | 2013-03-14 | University Of Virginia Patent Foundation | Molecular genetic approach to treatment and diagnosis of alcohol and drug dependence |
PE20141198A1 (es) | 2011-09-19 | 2014-10-05 | Orexo Ab | Nueva composicion farmaceutica resistente al abuso para el tratamiento de la dependencia de opioides |
EA028110B1 (ru) | 2012-05-02 | 2017-10-31 | Орексо Аб | Новая композиция альфентанила для лечения острой боли |
CN107595793B (zh) | 2012-11-30 | 2020-11-13 | 阿库拉制药公司 | 活性药物成分的自调节释放 |
US9572885B2 (en) | 2013-03-15 | 2017-02-21 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
KR20160108828A (ko) | 2013-11-11 | 2016-09-20 | 임팩스 라보라토리즈, 인코포레이티드 | 신속하게 붕괴되는 제형 및 사용 방법 |
US10722510B2 (en) | 2014-07-08 | 2020-07-28 | Hikma Pharmaceuticals Usa Inc. | Liquid naloxone spray |
CA2954370A1 (en) | 2014-07-08 | 2016-01-14 | Insys Pharma, Inc. | Sublingual naloxone spray |
US10617686B2 (en) | 2014-07-08 | 2020-04-14 | Hikma Pharmaceuticals Usa Inc. | Liquid naloxone spray |
MY187877A (en) | 2014-12-23 | 2021-10-26 | Acelrx Pharmaceuticals Inc | Systems, devices and methods for dispensing oral transmucosal dosage forms |
US9925138B2 (en) | 2015-01-20 | 2018-03-27 | Handa Pharmaceuticals, Llc | Stable solid fingolimod dosage forms |
WO2017040607A1 (en) | 2015-08-31 | 2017-03-09 | Acura Pharmaceuticals, Inc. | Methods and compositions for self-regulated release of active pharmaceutical ingredient |
EP3368084A4 (en) * | 2015-10-29 | 2019-07-03 | Solubest Ltd | PHARMACEUTICAL COMPOSITIONS FOR TRANSMUCOSAL RELEASE |
US10946020B2 (en) | 2016-04-06 | 2021-03-16 | University Of Virginia Patent Foundation | Compositions and methods for treating cancer |
Family Cites Families (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1548022A (en) * | 1976-10-06 | 1979-07-04 | Wyeth John & Brother Ltd | Pharmaceutial dosage forms |
US4206209A (en) * | 1978-11-02 | 1980-06-03 | Kracauer Paul | Sublingual aspirin tablet |
US4229447A (en) * | 1979-06-04 | 1980-10-21 | American Home Products Corporation | Intraoral methods of using benzodiazepines |
US4432975A (en) * | 1981-04-13 | 1984-02-21 | Icn Pharmaceuticals, Inc. | Process for introducing vitamin B-12 into the bloodstream |
DK152744C (da) * | 1982-08-13 | 1988-10-31 | Benzon As Alfred | Fremgangsmaade til fremstilling af et farmaceutisk peroralt polydepotpraeparat |
GB8332556D0 (en) * | 1983-12-06 | 1984-01-11 | Reckitt & Colmann Prod Ltd | Analgesic compositions |
US5288498A (en) * | 1985-05-01 | 1994-02-22 | University Of Utah Research Foundation | Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments |
US5288497A (en) * | 1985-05-01 | 1994-02-22 | The University Of Utah | Compositions of oral dissolvable medicaments |
GB8522453D0 (en) * | 1985-09-11 | 1985-10-16 | Lilly Industries Ltd | Chewable capsules |
DE3715682A1 (de) * | 1987-05-11 | 1988-11-24 | Stefan Dr Lueth | Vorrichtung zum herstellen eines zweikomponentengemisches |
SE8800080L (sv) * | 1988-01-13 | 1989-07-14 | Kabivitrum Ab | Laekemedelskomposition |
US5719197A (en) * | 1988-03-04 | 1998-02-17 | Noven Pharmaceuticals, Inc. | Compositions and methods for topical administration of pharmaceutically active agents |
US4866046A (en) * | 1988-05-31 | 1989-09-12 | Top Laboratories, Inc. | Low-dosage sublingual aspirin |
US5047244A (en) * | 1988-06-03 | 1991-09-10 | Watson Laboratories, Inc. | Mucoadhesive carrier for delivery of therapeutical agent |
SE8803935L (sv) * | 1988-10-31 | 1990-05-01 | Kabivitrum Ab | Laekemedelskomposition |
US5112616A (en) * | 1988-11-30 | 1992-05-12 | Schering Corporation | Fast dissolving buccal tablet |
CA2031376A1 (en) * | 1989-12-04 | 1991-06-05 | Bahram Farhadieh | Single layer transdermal drug administration system |
US5370862A (en) * | 1990-06-13 | 1994-12-06 | Schwarz Pharma Ag | Pharmaceutical hydrophilic spray containing nitroglycerin for treating angina |
FR2694194B1 (fr) | 1992-07-31 | 1994-11-04 | Health Business Dev | Gel hydratant, médicament et composition cosmétique le contenant, procédé de préparation dudit gel. |
JPH0665103A (ja) | 1992-08-13 | 1994-03-08 | ▲寛▼治 ▲高▼田 | 向精神薬のための速吸収性舌下投与製剤 |
EP0668764A1 (en) | 1992-09-21 | 1995-08-30 | QIN, Bo-yi | Methods for identifying and using low/non-addictive opioid analgesics |
US5631023A (en) | 1993-07-09 | 1997-05-20 | R.P. Scherer Corporation | Method for making freeze dried drug dosage forms |
GB9401894D0 (en) * | 1994-02-01 | 1994-03-30 | Rhone Poulenc Rorer Ltd | New compositions of matter |
US5948389A (en) * | 1995-06-07 | 1999-09-07 | El Khoury & Stein, Ltd. | Method of enhancing the analgesic efficacy of locally and topically administered opioids and other local anesthetics |
US5849322A (en) | 1995-10-23 | 1998-12-15 | Theratech, Inc. | Compositions and methods for buccal delivery of pharmaceutical agents |
US5733571A (en) * | 1995-12-08 | 1998-03-31 | Euro-Celtique, S.A. | Transdermal patch for comparative evaluations |
US5762961A (en) * | 1996-02-09 | 1998-06-09 | Quadrant Holdings Cambridge Ltd. | Rapidly soluble oral solid dosage forms, methods of making same, and compositions thereof |
US5747494A (en) * | 1996-06-28 | 1998-05-05 | U C B S.A. | Pharmaceutical compositions for the treatment of depressive disorders |
DE19652188C2 (de) | 1996-12-16 | 2002-02-14 | Lohmann Therapie Syst Lts | Flache Arzneizubereitung zur Applikation und Freisetzung von Buprenorphin oder einer pharmakologisch vergleichbaren Substanz in der Mundhöhle und Verfahren zu ihrer Herstellung |
DE19652268C2 (de) | 1996-12-16 | 2000-06-29 | Lohmann Therapie Syst Lts | Arzneizubereitung für die Freisetzung von Apomorphin in der Mundhöhle |
FR2758459B1 (fr) * | 1997-01-17 | 1999-05-07 | Pharma Pass | Composition pharmaceutique de fenofibrate presentant une biodisponibilite elevee et son procede de preparation |
US5968547A (en) * | 1997-02-24 | 1999-10-19 | Euro-Celtique, S.A. | Method of providing sustained analgesia with buprenorphine |
DE19758564A1 (de) * | 1997-11-11 | 1999-08-26 | Gruenenthal Gmbh | Formulierung einer Kombination aus Morphin und einem alpha¶2¶-adrenergem Agonisten und deren Verwendung |
KR100289471B1 (ko) * | 1998-01-19 | 2001-09-17 | 김충섭 | 휀타닐계마취제의이식형서방성제제 |
US6974590B2 (en) * | 1998-03-27 | 2005-12-13 | Cima Labs Inc. | Sublingual buccal effervescent |
US6264974B1 (en) * | 1998-07-07 | 2001-07-24 | Salvagnini Italia Spa | Buccal and sublingual administration of physostigmine |
SE9803239D0 (sv) * | 1998-09-24 | 1998-09-24 | Diabact Ab | Composition for the treatment of acute pain |
SE9803240D0 (sv) | 1998-09-24 | 1998-09-24 | Diabact Ab | A pharmaceutical composition having a rapid action |
EP1005863A1 (en) | 1998-12-04 | 2000-06-07 | Synthelabo | Controlled-release dosage forms comprising a short acting hypnotic or a salt thereof |
WO2001030391A2 (en) | 1999-10-27 | 2001-05-03 | Farmarc Nederland Bv | Pharmaceutical composition containing midazolam |
AU5066101A (en) * | 2000-04-13 | 2001-10-30 | Synthon B.V. | Modified release formulations containing a hypnotic agent |
CN1290525A (zh) | 2000-10-10 | 2001-04-11 | 北京万全阳光医药科技有限公司 | 冷冻干燥的扎来普隆速溶口服组合物 |
US20030035839A1 (en) | 2001-05-15 | 2003-02-20 | Peirce Management, Llc | Pharmaceutical composition for both intraoral and oral administration |
MXPA04006779A (es) | 2002-01-10 | 2005-04-25 | Biovail Lab Inc | Formulaciones de sedantes no benzodiazepinicos. |
CN1418631A (zh) | 2002-12-19 | 2003-05-21 | 王登之 | 治疗失眠的佐匹克隆口腔崩解片及其制备方法 |
US20040265375A1 (en) | 2003-04-16 | 2004-12-30 | Platteeuw Johannes J. | Orally disintegrating tablets |
-
1998
- 1998-09-24 SE SE9803240A patent/SE9803240D0/xx unknown
-
1999
- 1999-09-24 RU RU2001111025/14A patent/RU2193879C1/ru active
- 1999-09-24 MX MXPA01003068A patent/MXPA01003068A/es active IP Right Grant
- 1999-09-24 KR KR1020017003715A patent/KR100760536B1/ko active IP Right Grant
- 1999-09-24 EE EEP200800028A patent/EE05555B1/xx unknown
- 1999-09-24 EE EEP200100182A patent/EE04927B1/xx unknown
- 1999-09-24 DE DE69936393T patent/DE69936393T2/de not_active Expired - Lifetime
- 1999-09-24 JP JP2000573711A patent/JP3381220B2/ja not_active Expired - Lifetime
- 1999-09-24 IL IL14213599A patent/IL142135A0/xx not_active IP Right Cessation
- 1999-09-24 PT PT141750851T patent/PT2805716T/pt unknown
- 1999-09-24 EP EP14175085.1A patent/EP2805716B1/en not_active Revoked
- 1999-09-24 HU HU0103856A patent/HU230342B1/hu unknown
- 1999-09-24 CZ CZ20011029A patent/CZ302975B6/cs not_active IP Right Cessation
- 1999-09-24 PT PT50778752T patent/PT1652518E/pt unknown
- 1999-09-24 PL PL383971A patent/PL204264B1/pl unknown
- 1999-09-24 EP EP99952867A patent/EP1115383B1/en not_active Expired - Lifetime
- 1999-09-24 WO PCT/SE1999/001687 patent/WO2000016750A1/en active Application Filing
- 1999-09-24 CA CA002345121A patent/CA2345121C/en not_active Expired - Lifetime
- 1999-09-24 SK SK402-2001A patent/SK283302B6/sk not_active IP Right Cessation
- 1999-09-24 EE EEP200700030A patent/EE05023B1/xx unknown
- 1999-09-24 DK DK10001406.7T patent/DK2236132T3/da active
- 1999-09-24 DK DK10001408.3T patent/DK2236133T3/da active
- 1999-09-24 CA CA2629988A patent/CA2629988C/en not_active Expired - Lifetime
- 1999-09-24 PT PT100014067T patent/PT2236132E/pt unknown
- 1999-09-24 AT AT99952867T patent/ATE365540T1/de active
- 1999-09-24 HU HU0800435A patent/HU230468B1/hu unknown
- 1999-09-24 ES ES10001406.7T patent/ES2507579T3/es not_active Expired - Lifetime
- 1999-09-24 TR TR2001/00855T patent/TR200100855T2/xx unknown
- 1999-09-24 PT PT99952867T patent/PT1115383E/pt unknown
- 1999-09-24 CZ CZ2008-315A patent/CZ2008315A3/cs not_active IP Right Cessation
- 1999-09-24 EP EP10001408.3A patent/EP2236133B1/en not_active Expired - Lifetime
- 1999-09-24 ES ES99952867T patent/ES2289829T3/es not_active Expired - Lifetime
- 1999-09-24 CN CNB998135453A patent/CN1173694C/zh not_active Expired - Lifetime
- 1999-09-24 US US09/787,888 patent/US6761910B1/en not_active Expired - Lifetime
- 1999-09-24 EP EP05077875.2A patent/EP1652518B1/en not_active Expired - Lifetime
- 1999-09-24 PL PL347126A patent/PL201644B1/pl unknown
- 1999-09-24 ES ES14175085.1T patent/ES2644770T3/es not_active Expired - Lifetime
- 1999-09-24 ES ES05077875T patent/ES2433930T3/es not_active Expired - Lifetime
- 1999-09-24 NZ NZ510284A patent/NZ510284A/en not_active IP Right Cessation
- 1999-09-24 DK DK99952867T patent/DK1115383T3/da active
- 1999-09-24 BR BRPI9913945A patent/BRPI9913945B8/pt not_active IP Right Cessation
- 1999-09-24 CA CA2820588A patent/CA2820588C/en not_active Expired - Lifetime
- 1999-09-24 AU AU64927/99A patent/AU764346B2/en active Active
- 1999-09-24 EP EP10001406.7A patent/EP2236132B1/en not_active Expired - Lifetime
- 1999-09-24 DK DK14175085.1T patent/DK2805716T3/en active
- 1999-09-24 ES ES10001408.3T patent/ES2498095T3/es not_active Expired - Lifetime
- 1999-09-24 DK DK05077875.2T patent/DK1652518T3/da active
- 1999-09-24 PT PT100014083T patent/PT2236133E/pt unknown
-
2001
- 2001-03-22 NO NO20011473A patent/NO332226B1/no not_active IP Right Cessation
- 2001-03-23 BG BG105379A patent/BG65502B1/bg unknown
-
2004
- 2004-05-24 US US10/851,215 patent/US20040213855A1/en not_active Abandoned
-
2006
- 2006-10-10 US US11/544,660 patent/US7910132B2/en not_active Expired - Fee Related
- 2006-10-25 HK HK06111773.4A patent/HK1091722A1/xx not_active IP Right Cessation
- 2006-10-25 HK HK11102568.5A patent/HK1148458A1/zh not_active IP Right Cessation
- 2006-10-25 HK HK11102567.6A patent/HK1148457A1/zh not_active IP Right Cessation
-
2007
- 2007-08-07 CY CY20071101054T patent/CY1107711T1/el unknown
-
2008
- 2008-07-01 US US12/216,197 patent/US20080286368A1/en not_active Abandoned
-
2011
- 2011-11-22 US US13/302,720 patent/US8512747B2/en not_active Expired - Fee Related
- 2011-11-22 US US13/302,694 patent/US8454996B2/en not_active Expired - Fee Related
-
2013
- 2013-03-13 US US13/799,640 patent/US20130195976A1/en not_active Abandoned
- 2013-07-30 US US13/954,141 patent/US20140030336A1/en not_active Abandoned
- 2013-11-04 CY CY20131100974T patent/CY1114620T1/el unknown
-
2014
- 2014-08-04 CY CY20141100588T patent/CY1115685T1/el unknown
- 2014-09-10 CY CY20141100730T patent/CY1115688T1/el unknown
-
2015
- 2015-01-20 LU LU92636C patent/LU92636I2/xx unknown
- 2015-04-14 HK HK15103632.1A patent/HK1203144A1/zh not_active IP Right Cessation
-
2017
- 2017-11-30 CY CY20171101261T patent/CY1119644T1/el unknown
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102582106A (zh) * | 2006-05-23 | 2012-07-18 | 奥拉黑尔斯公司 | 具有阿拉伯树胶粘合剂的双层口用粘附性片剂 |
CN102582106B (zh) * | 2006-05-23 | 2015-12-16 | 奥拉黑尔斯公司 | 具有阿拉伯树胶粘合剂的双层口用粘附性片剂 |
CN107157994A (zh) * | 2017-06-09 | 2017-09-15 | 董鹏 | 一种托拉塞米的舌下口服制剂 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1173694C (zh) | 用于治疗急性疾病的药用组合物 | |
CN1170524C (zh) | 用于治疗急性疼痛的芬太尼化合物 | |
MXPA01003063A (en) | Fentanyl composition for the treatment of acute pain |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
C10 | Entry into substantive examination | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term | ||
CX01 | Expiry of patent term |
Granted publication date: 20041103 |