CN101272762B - 胺聚合物的小袋制剂 - Google Patents
胺聚合物的小袋制剂 Download PDFInfo
- Publication number
- CN101272762B CN101272762B CN2006800340717A CN200680034071A CN101272762B CN 101272762 B CN101272762 B CN 101272762B CN 2006800340717 A CN2006800340717 A CN 2006800340717A CN 200680034071 A CN200680034071 A CN 200680034071A CN 101272762 B CN101272762 B CN 101272762B
- Authority
- CN
- China
- Prior art keywords
- powder
- powder formulation
- aliphatic amine
- amine polymer
- polymer
- 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.)
- Active
Links
Classifications
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
- A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
-
- 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
- A61K31/74—Synthetic polymeric materials
-
- 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
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- 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
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- 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
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8105—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/817—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions or derivatives of such polymers, e.g. vinylimidazol, vinylcaprolactame, allylamines (Polyquaternium 6)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/89—Polysiloxanes
- A61K8/896—Polysiloxanes containing atoms other than silicon, carbon, oxygen and hydrogen, e.g. dimethicone copolyol phosphate
- A61K8/898—Polysiloxanes containing atoms other than silicon, carbon, oxygen and hydrogen, e.g. dimethicone copolyol phosphate containing nitrogen, e.g. amodimethicone, trimethyl silyl amodimethicone or dimethicone propyl PG-betaine
Abstract
一种包括药学上可接受的阴离子稳定剂和一种与阴离子稳定剂混合的脂肪胺聚合物或其药学上可接受的盐的粉末制剂。粉末制剂方便地包装于一种容器中,如一种小袋。也描述了使用粉末制剂治疗患有高磷酸盐血症的主体的方法。
Description
背景技术
脂肪胺聚合物作为磷酸盐结合物是有效的,并已经在许多情况中被描述(见美国专利号5496545和5667775)。例如,盐酸司维拉姆,一种交联多聚(丙烯胺)聚合物,目前以商标RENAGEL出售以去除病人体内的磷酸盐。脂肪胺聚合物已经在高胆固醇血症的治疗中被描述(见美国专利号5624963和5679717及PCT公开号WO98/29107和WO99/22721)。例如,考来维仑,一种烷基化,交联聚合(丙烯胺),目前以商标WELCHOL出售以减少血清胆固醇。
但是,上述产品目前仅以片剂的形式被使用,某些病人可能更适合于使用该产品的其他剂量形式进行治疗。
发明内容
本发明主要提供了,脂肪胺聚合物的新组分和制剂。其中一种制剂是一种可以与水混合(熔解或悬浮)并口服给药的粉末制剂,并对于病人的口感和味道具有可接受的特点。这些制剂的应用已经被发现,一种药学上可接受的的阴离子稳定剂,当与脂肪胺聚合物混合时,可以提供脂肪胺聚合物的可接受的口感。这里描述了基于本发明的一种脂肪胺聚合物或其药学上可接受的盐的新型粉末制剂,和含有制剂粉末的容器和用制剂粉末治疗患有高磷酸盐血症病人的方法。
一个实施方案,本发明提供了含有粉末的容器,其包括药学上可接受的阴离子稳定剂和与阴离子稳定剂混合的脂肪胺聚合物或其药学上可接受的盐。粉末是未充气的和自由流动的。
另一实施方案,本发明是包括一种一个药学上可接受的阴离子稳定剂和一种一个与药学上可接受的阴离子稳定剂混合的脂肪胺聚合物或其药学上可接受的盐的粉末制剂。优选地,粉末中仅有的药物活性成分是脂肪胺聚合物。
本发明也提供了治疗患有高磷酸盐血症病人的方法。方法包括对病人用描述的粉末制剂口服给药步骤。
具体实施方式
所描述的粉末形式包括一种脂肪胺聚合物和一种药学上可接受的阴离子稳定剂以提供可接受的口感。粉末制剂在可吸收的液体,如水中是可溶和/或可悬浮的,从而可以方便地对病人通过喝水给药。液体可以用一种或多种甜味剂和/或使用香料增加口感。这些粉末制剂乐意方便地包装于容器中,如袋或小桶中。这里使用的,术语“粉末”和“粉末制剂”可交替使用。
本发明的粉末制剂可以进一步包括使用香料,甜味剂,赋形剂,填充剂,惰性成分和类似物。
这里使用的“一种药学上可接受的阴离子稳定剂”是一种包括一个酸性功能团(例如,羧酸,磺酸,磷酸和类似物,或其药学上可接受的盐)的化合物,并可以充分的改善脂肪胺聚合物的口感。酸性功能团可选地可被一种或多种药学上可接受的有机或无机碱中和以形成药学上可接受的盐。当药学上可接受的阴离子稳定剂包括一种以上酸性功能基团时,酸性功能基团可以部分或 完全被中和。可选地,一些酸性功能基团可以容易地制备成酸性功能基团的酯。以下描述了有机或无机碱的实施例。
药学上可接受的阴离子稳定剂典型地具有大于1mg/ml和pKa值小于9的水溶性。药学上可接受的阴离子稳定剂应当不干扰脂肪胺聚合物的治疗活性,并且在给药的剂量上不产生无法接受的副作用。
只要具有上述的特点,药学上可接受的阴离子稳定剂的分子量在本发明中是非关键的。典型地,药学上可接受的阴离子稳定剂的分子量大于1000道尔顿。当药学上可接受的阴离子稳定剂的分子量大于1000道尔顿时,每1000道尔顿药学上可接受的阴离子稳定剂的离子密度典型地等于或大于1。
药学上可接受的阴离子稳定剂可以不是一种“药物活性成分”。
一个实施方案,药学上可接受的的阴离子稳定剂是一种阴离子聚合体,如一种阴离子多肽(例如,一种蛋白),一种阴离子多糖或一种或多种阴离子单体的聚合物。阴离子聚合物的实施例包括聚甘露糖醛酸,古罗糖醛酸,谷氨酸或其组合物,和其药学上可接受的盐。其他阴离子聚合物的实施例包括纤维素,如羧烷基纤维素或其药学上可接受的盐。一种阴离子聚合物可以是均聚物或两种上述单体的共聚物。可选地,阴离子共聚物包括一种或多种上述的阴离子单体单元和一种或多种适宜的惰性和无毒性的中性共聚单体。可以使用的合适的中性共聚单体实施例,例如,烯阴离子单体,包括乙烯醇,丙烯酰胺和乙烯甲酰胺。阴离子聚合物的特殊实施例包括海藻酸盐(例如,海藻酸钠,海藻酸钾,海藻酸钙,海藻酸镁,海藻酸胺,海藻酸的酯,等),羧甲基纤 维素,聚乳酸,聚谷氨酸,胶质,黄原胶,角菜胶,帚叉藻胶,阿拉伯胶,卡拉牙胶,加特胶,豆角树胶和黄蓍胶。
在一钟优选实施方案中,阴离子聚合物是一种海藻酸,更适合的为酯化海藻酸,如海藻酸的C2-C5-二醇酯或海藻酸C3-C5-三醇酯。这里使用的,“酯化海藻酸”指海藻酸上的一些羧基被酯化的海藻酸。剩余的羧基基团被中和(部分或完全)为药学上可接受的盐。例如,藻酸丙二醇酯是一种部分羧基基团被丙二醇酯化的海藻酸酯,而剩余的羧酸基团被任意地中和(部分或完全)为药学上可接受的盐。更合适地,阴离子聚合物是海藻酸乙二醇酯,藻酸丙二醇酯或海藻酸甘油酯。藻酸丙二醇酯是更合适的。
如以上说明的,阴离子聚合物可以用于制备药学上可接受的盐(完全或部分中和)。这里使用的,一种“药学上可接受的盐”指由药学上可接受的酸或碱制备的盐。例如,具有充分的酸性功能基团的阴离子聚合物可以与任何数量的药学上可接受的有机或无机碱反应生成盐。盐的实施例包括碱金属和稀土金属,如钠,钙,镁和钾;锌;和胺盐。混合盐也包括在其中。“胺”可以表示为NR’4 +,其中R’是-H或替代的或未替代的,线性或环形,或饱和或不饱和烷基,芳基或araryl。胺的实施例包括NH4 +和N(R’)H3 +,N(R’)2H2 +,N(R’)3H+和N(R’)4 +,其中R’是C1-C10烷基或苯基。
另一实施方案,药学上可接受的阴离子稳定剂是一种阴离子多肽,包括一种蛋白。阴离子多肽的实施例包括明胶,酪蛋白消化物,乳清蛋白,大豆蛋白和聚谷氨酸。
一种或多种药学上可接受的阴离子稳定剂可以用于本发明。
本发明的粉末制剂典型地包括重量比为0.005-99.9∶1的药学上可接受的阴离子稳定剂和脂肪胺聚合物,如0.005-50∶1,0.005-10∶1;0.005-3∶1,0.005-1∶1,0.005-0.5∶1,和0.008-0.05∶1。
脂肪胺聚合物以包括至少一个胺基的重复单元为特点。胺基可以是聚合物骨架的一部分(例如,聚烯亚胺如聚乙烯亚胺)或聚合物骨架侧链(例如,聚烯丙胺)。可选地,两种类型的胺基可以带有相同的重复单元和/或聚合物。这里使用的术语“胺基”,包括伯胺,仲胺和叔胺,以及铵根如三烷基季胺。
脂肪胺聚合物可以通过将脂肪胺单体聚合而获得。脂肪胺可以是具有一个胺基取代和可选地一个或更多额外取代的,饱和或非饱和的,直-链的,分支或环形非-芳香烃。一种脂肪胺单体聚合物是一种包括聚合基团如石蜡的脂肪胺。合适的脂肪胺聚合物描述于美国专利第5487888号,第5496545号,第5607669号,第5618530号,第5624963号,第5667775号,第5679717号,第5703188号,第5702696号,第5693675号,第5900475号,第5925379号,第6083497号,第6177478号,第6083495号,第6203785号,第6423754号,第6509013号,第6605270号,第6726905号,第6733780号和第6858203号和美国公开专利申请第2002/0159969A1号和第2003/0086898A1号,其内容通过在此引述全部合并入本文。
脂肪胺聚合物可以是单体聚合物或由一种或多种更多含有胺基的单体的共聚物,或一种或多种含有胺基的单体的共聚物,其与含有一种或多种非-胺基的单体结合,其是合适地的惰性的和非-毒性的。合适的非-胺基单体的实施例包括乙烯醇,丙烯酸,丙烯酰胺,和乙烯甲酰胺。
脂肪胺聚合物的实施例包括具有一种或多种从由结构式(1)-(6)中选择的重复单元的聚合物:
或其盐或共聚物,其中y是零或一个或多个整数(例如,1至10之间,优选地在1和4之间,更优选地为1),而每个R,R1,R2,和R3,独立的,为H,一种取代或非取代烷基(例如,具有1至25或1至5个碳原子,包括)或芳香基(例如,苯基),而每个X-是交换性负电荷反离子。
优选地,R,R1,R2,和R3至少一种是氢原子。更适宜地,每个基团都是氢。
以R,R1,R2,和R3表示的烷基或芳香基,可以带有一个或多个取代。合适的替包括阴离子基团,例如,季铵,或胺基,例如,伯烷,仲烷或叔烷或芳香胺。其他合适的取代的实施例包括羟基,烷氧基,甲酰胺,磺胺,卤素,烷基,芳香基,肼,胍,尿素,聚(烯烃亚胺)如聚(乙烯亚胺),和羧酸酯。
优选地,脂肪胺聚合物是一种均聚物,如均聚丙烯酰胺,均聚乙烯胺,均聚二烯丙基胺或聚亚乙基胺。
在一个实施方案中,脂肪胺聚合物是一种以结构式(7)的一种或多种重复单元为特征的均聚物或共聚物:
或其药学上可接受的盐,其中x是0或1和4之间的整数。由结构式(7)表示的聚合物可以方便的通过交联试剂进行交联。
本发明中使用的一个优选的脂肪胺聚合物是聚丙烯胺,其是一种具有来源于聚合的烯丙基胺基单体重复单元的聚合物。烯丙基单体的胺基基团可以非取代或被取代,例如,被一个或两个C1-C10直链或分支烷基基团取代。这些烷基基团可选地被一个或多个羟基,胺基,haio,苯基,胺基或腈基。优选地,本发明的脂肪胺聚合物是包括由结构式(8)表示的重复单元的聚烯丙胺聚合物:
可以用于本发明的脂肪胺聚合物的聚烯丙胺可以包括共聚物,其包括来源于两种或多种不同聚合烯丙基单体的重复单元,或来源于一种或多种聚合烯丙基单体的重复单元,或来源于一种或多种聚合非-烯丙基单体的重复单元。合适的非-烯丙基单体的实施例包括丙烯酰胺单体,丙烯酸盐单体,马来酸,malimide 单体,乙烯酰单体和烷基取代的烯烃。优选地,然而,本发明中使用的聚烯丙胺包括来源于聚合烯丙基胺单体的独立重复单元。更优选地,本发明中使用的聚烯丙胺聚合物是均聚物。更优选地,本发明中使用的聚烯丙胺聚合物是由结构式(8)表示的重复单元的均聚物。描述的发明中使用的聚烯丙胺聚合物优选地是交联聚合物,更优选地是交联均聚物。
在另一实施方案中,脂肪胺聚合物可以是聚丁烯胺,聚赖氨酸,或聚精氨酸。
优选地,脂肪胺聚合物通过与交联试剂进行交联成为水-不溶性。合适的交联试剂包括那些带有与脂肪胺聚合物胺基反应的功能基团的试剂。可选地,交联试剂可以含有两种或多种乙烯基团,其可以与胺单体进行自由基本聚合。一些情况下脂肪胺聚合物在聚合后交联。
脂肪胺聚合物典型地与非功能交联试剂交联。合适的交联试剂的实施例包括丙烯酸酯和二甲基丙烯酸酯(例如,乙二醇二丙烯酸酯,丙二醇二丙烯酸酯,丁二醇二丙烯酸酯,乙二醇二甲基丙烯酸酯,丙乙二醇二甲基丙烯酸酯,丁二醇二甲基丙烯酸酯,聚乙二醇二甲基丙烯酸酯,聚乙二醇丙烯酸酯),亚甲基双丙烯酰胺,亚甲基二甲基双丙烯酰胺,乙烯双丙烯酰胺,乙烯二甲基双丙烯酰胺,亚乙基双丙烯酰胺,二乙烯基苯,双酚A,双酚A的二缩水甘油醚,均苯四酸二酐,甲苯二异氰酸酯,乙二胺和丁二酸二甲酯,二甲基丙烯酸酯和双酚A二丙烯酸酯。优选的非功能交联试剂包括环氧氯丙烷,1,4丁二醇二缩水甘油醚,1,2乙二醇二缩水甘油醚,1,3-二氯丙烷,1,2-二氯乙烷,1,3-二溴丙烷,1,2-二溴乙烷,琥珀酰氯,丁二酸二甲酯,甲苯二异氰酸酯,丙烯酰氯,和均苯四酸二酐。环氧氯丙烷由于其高效性和低成本是一种最优选的交联试剂。环氧氯丙烷由于其低分子 量和亲水性而具有优势性,增加了水-膨胀性和聚胺的凝胶特性。环氧氯丙烷形成2-羟丙基交联基团。
其他在已经聚合的材料中引导交联的方法包括,但不局限于,暴露于电离辐射,紫外辐射,电子束,自由基和热裂解。
交联的水平使得脂肪胺聚合物不可溶并充分具有吸收和降解抗性,因此限制了脂肪胺聚合物对胃肠道的活性,并减少了病人中潜在的副作用。典型地,交联试剂在数量中的百分比为重量的0.5-35%或约0.5-25%(如从2.5-20%或约1-10%),基于脂肪胺聚合物加上交联试剂的全部重量。典型地,交联试剂的数量以占作为脂肪胺聚合物和交联试剂的联合重量的百分数测定。
典型地,大约9%至30%的丙烯基氮原子与交联基团结合,优选地在15%至21%之间。
脂肪胺聚合物也可以进一步派生;实施例包括烷胺聚合物,如描述的,例如,United States Patent Nos.56797175607669和5618530,其技术通过在此引述全部合并入本文。优选的烷基化试剂包括疏水基团(如脂肪族疏水基团)和/或季铵-或胺-取代烷基。
非-交联和交联聚烯丙胺和聚乙烯胺在本领域中通常已知并且可商业获得。生产聚烯丙胺和聚乙烯胺,和其交联派生物的方法,描述于上述的美国专利。Harada等的专利,(美国专利第4605701号和第458347号),其通过在此引述全部合并入本文,同时也描述了生产聚烯丙胺和交联聚烯丙胺的方法。Stutts等的专利(美国专利第6180754号)描述了生产交联聚烯丙胺的额外方法。
通常不认为脂肪胺聚合物的分子重量是十分重要的,只要分子量足够大使得脂肪胺聚合物通过胃肠道时是非-吸收的。典型地,脂肪胺聚合物的分子重量至少为1000。例如分子量可以从:约1000至约5000000,约1000至约3000000,约1000至约2000000或约1000至约1000000。
本发明使用的脂肪胺聚合物可以随意地质子化,一个实施方案中,少于40%的聚合物,例如,少于30%,如少于20%或少于10%的胺基被质子化。另一实施方案中35%至45%的胺被质子化(例如,大约40%)。合适的质子化脂肪胺聚合物的实施例是司维拉姆。
如上所述,脂肪胺聚合物可以以药学上可接受的盐的形式给药。术语“药学上可接受的盐”指所施用的由药学上可接受的非-毒性酸,包括无机酸,有机酸,溶剂化物,氢氧化物,或其包含物制备的脂肪胺聚合物的盐。这样,脂肪胺聚合物中的氮基团被质子化以生成与阴性电荷反离子相关的阳性电荷氮原子。
合适的反离子包括有机离子,无机离子,或其组合物。例如,合适的反离子包括卤化物(例如,F-,Cl-,Br-和I-),CH3OSO3 -,HSO4 -,SO4 2-,HCO3 -,CO3 2-,醋酸盐,乳酸盐,琥珀酸盐,丙酸盐,草酸盐,丁酸盐,抗坏血酸盐,柠檬酸盐,磷酸二氢柠檬酸盐,酒石酸盐,牛磺胆酸盐,甘氨胆酸盐,胆酸盐,一水柠檬酸盐,马来酸盐,苯甲酸盐,叶酸盐,一种氨基酸派生物,一种核苷,一种脂,或一种磷脂。优选的阴离子是Cl-,HCO3 -,CO3 2-,和其组合物(例如,混合碳酸盐和重碳酸盐,混合碳酸盐和氯化盐,或混合重碳酸盐和氯化盐)。反离子相互间也可以相同,或不同。例如,聚合物可以含有两种或多种不同类型的反离子。
一个优选实施方案中,本发明中使用的脂肪胺聚合物是一种表氯醇交联聚丙烯胺,如司维拉姆和考来维仑(见,例如,美国专利第6423754号;第5607669号;和第5679717号,其通过在此引述全部合并入本文)。一个优选实施方案,聚丙烯胺聚合物与表氯醇交联并且9%至30%(优选地为15%至21%)的烯丙基氮原子与交联基团结合并且阴离子是氯化物,碳酸盐或重碳酸盐或其盐的混合物。
一个特别优选的脂肪胺聚合物是与以9.0-9.8%,优选地为9.3-9.5%重量/重量的表氯醇交联的盐酸聚丙烯胺聚合物,并且是司维拉姆HCl药物的活性化学成分,以商品名RENAGEL出售。结构式表示如下:
其中:
a和b的总数(原初胺基团组)是9;
c(交联基团的数量)是1;
n(质子化胺片断)是0.4;并且
m是一个大数量(表明扩展的聚合体网络)。
另一特别优选实施方案中,脂肪胺聚合物是司维拉姆的碳酸盐;司维拉姆的重碳酸盐;司维拉姆碳酸盐和重碳酸盐的混合物;或司维拉姆的碳酸盐和氯盐混合物。
另一实施方案,单价阴离子源与脂肪胺聚合物的碳酸盐混合。脂肪胺聚合物碳酸盐和单价阴离子源的多种实施例描述于美国临时申请号60/624001“制药片的脂肪胺聚合物”,2004,11月1日归档,及美国临时申请号60/628752“制药片的脂肪胺聚合盐”,2004,11月17日归档,其通过在此引物全部合并与本文。
单体阴离子至少为脂肪胺聚合物碳酸盐和单体阴离子源联合重量的0.01%,优选地为0.05%,更优选地为0.01%至2%,0.05%至1%,0.08%至0.5%,或0.1%至0.3%。
合适的单体阴离子包括有机离子,无机离子,或其组合物,如卤化物(Cl-,I-,FI-和Br-),CH3OSO3 -,HSO4 -,醋酸盐,乳酸盐,丁酸盐,丙酸盐,硫酸盐,柠檬酸盐,酒石酸盐,硝酸盐,磺酸盐,草酸盐,琥珀酸盐。优选的单体阴离子是卤化物,更优选的为氯化物。
单价阴离子源可以是药学上可接受的酸,单价阴离子的胺或金属盐。优选地单价阴离子源是氯化钠或盐酸。一个优选实施方案,发明的制剂包括司维拉姆的碳酸盐和氯化钠。另一实施方案,发明的制剂包括司维拉姆的碳酸盐和盐酸。
另一优选实施方案,单价阴离子源可以是单价阴离子盐或包括上述(1)-(8)结构式表示的重复单元的脂肪胺聚合物。发明的制剂可以包括“物理混合聚合物”或“化学混合聚合物”。脂肪胺聚合物的碳酸盐和脂肪胺聚合物的单价阴离子盐的组合在此被定义为“物理混合聚合物”。脂肪胺聚合物的单价阴离子盐可以是相同或不同的脂肪胺聚合物,如脂肪胺聚合物碳酸盐。这里,“化学混合聚合物”指单个脂肪胺聚合物上碳酸盐和单价阴离子的组合。
一些实施方案中,脂肪胺聚合物或其药学上可接受的盐是粉末制剂中仅有的药物活性成分。
用于病人的发明的粉末制剂包括脂肪胺聚合物和药学上可接受的阴离子稳定剂,可选地与一种或多种可接受的赋形剂联合。赋形剂包括载体或稀释剂,如乳糖,淀粉,纤维素和葡萄糖;增味剂;甜味剂;和防腐剂,如对羟基苯甲酸甲酯,对羟基苯甲酸乙,甲酯对羟基苯甲酸丙酯和对羟基苯甲酸丁酯。可选地,为了改善外观,赋形剂,如微晶纤维素,二氧化钛,和/或着色剂,如FD&C Red#40,D&C Yellow#10,D&C Red#33,或氧化铁黄,也可以包括在发明的粉末制剂中,合适的甜味剂的实施例包括蔗糖;葡萄糖(玉米糖浆);右旋糖;转化糖;果糖;糖精和其各种盐,如糖精钠;钠,天冬氨酰苯丙氨酸甲酯,木糖;麦芽糖醇,麦芽醇,乙酰磺胺钾;新橙皮甙二氢查尔酮,甘草酸单铵,麦芽糊精和聚葡萄糖糖精和其各种盐如钠和钾盐;环己氨磺酸和其各种盐;二肽甜味剂;三氯蔗糖;二氢查耳酮甙,甘草酸;甜菊(甜菊甙);山梨醇;甘露醇;木糖醇;六-间苯二酚;氢化淀粉水解产物(lycasin),和3,6-二氢-6-甲基-1-1,2,3-氧恶嗪-4-on3H-2,2-二氧化物,和其混合物。上述中,无论单独或组合,三氯蔗糖,蔗糖,木糖,甘露醇,麦芽糖醇,麦芽醇,山梨醇, 木糖醇是特别优选的。合适的调味剂包括葡萄,樱桃,薄荷,薄荷脑,香草香味,如橙子香草香味,柠檬香味荷兰薄荷,冬季青绿,肉桂,薄荷酮香精,或其混合物。赋形剂必须与其他制剂成分相容“可接受”并对接受者无害。
典型地,发明的粉末的平均颗粒大小小于500微米,优选地小于200微米。一些实施方案中,粉末含有少于5wt%,优选地少于2wt%,更优选地大小大于300微米的颗粒少于1wt%,更合适的大小少于10微米的颗粒小于1wt%。
描述的粉末制剂典型地熔解和/或悬浮于可吸收液体如水中。最后的混合物具有良好的口感并因此可以方便地通过喝入对病人给药。液体可以是悬液或溶液。液体可以用一种或多种甜味剂和/或增味剂增加美味。可选地,描述的粉末制剂可以与食物混合,如捣碎的土豆或麦片。
发明的粉末制剂可以方便地包装入容器中。这里,“容器”是一种非-有害的包装装置,其可以在充分长的时间内装载在和保护发明的粉末制剂的稳定性,例如,从生产的时间至病人给药的时间。如上所述,粉末制剂是非胶囊包裹的并且是自由-流动的。本发明合适的容器包括小袋,如纸袋,塑料膜或金属箔粉末袋;瓶子,如玻璃,塑料或金属瓶;管子;安瓿瓶。优选地,发明的容器是一个小袋。合适地,容器材料对水和水蒸气是不渗透的,以确保容器中活性药物的稳定性。可选地,容器材料可以含有具有特定保护类型的物质,例如避光。合适的容器材料的实施例包括塑料,如MATTLACQUER/PET 23μ/PX 12GR/AL 12μ/SURLYN23GR(AMCOR Flexibles in Victoria,澳大利亚),包裹纸,如包裹纸40GR/PX 12GR/AL 12μ/SURLYN23GR(AMCORFlexibles in Victoria,澳大利亚),铝箔袋,如 TPC-2475(PA,Feasterville的TOLAS健康保护包装),和这些其材料的组合(例如,碾压)。
优选地,容器是一种具有上述多层不同材料的多层容器。
含有发明的粉末制剂的容器可以是单-剂量或多-剂量容器。例如,发明的容器可以包括单剂量的与药学上可接受的阴离子稳定剂混合的脂肪胺聚合物,如单-剂量小袋。可选地,发明的容器可以含有至少双剂量的与药学上可接受的阴离子稳定剂混合的脂肪胺聚合物,如瓶或管,其中通过例如勺或杯子,或可以分配预-定义剂量的装置测定单位剂量。这里,“管子”指含有大数量粉末制剂的容器。“大数量”指可以分成许多单位剂量的数量,例如,2,10,50,100或更多单位剂量。
发明的粉末制剂可以通过药品领域中任何已知的方法制备。例如,可以使用标准的药物制备技术,如描述于Remington’s药物科学,18th ed(1990),Mack出版公司,Easton,PA,其描述通过在此引述全部合并与本文。典型地,方法包括将至少一种脂肪胺聚合物与一种或多种药学上可接受的阴离子稳定剂混合的步骤,并与任何额外赋形剂混合制备最后的混合物。通常,通过将脂肪胺聚合物均一地紧密地与药学上可接受的阴离子稳定剂结合二制备,如果需要,将产物分成单位剂量。粉末制剂用合适的容器包装,如小袋。
典型地,如果每天给药一次,容器装有一单元剂量的通常为5mg至15g(例如,600mg-7.5g,600mg-5g,800mg-3.5g和800mg-2.5g)干燥形式的脂肪胺聚合物。典型地,约0.025mg至约14.9g(例如,3mg-7.5g;3ml-5g;8mg-3.5g;8mg-2.5g;6mg-2.5g,6mg-1.5g,6mg-0.75g)药学上可接受的阴离子稳定剂包括于脂肪胺聚合物的单元剂量中。可选地,容器中的单位剂量通 常是按每日给药次数划分的日剂量,如果每天多次给药(例如,2,3,4,5次/天)。一个实施例中,小袋含有800mg,1.6g,2.4g,3.2g,4.0g,4.8g,5.6g,7.2g或9.6g无水司维拉姆,并进一步包括海藻酸丙二醇酯和合适的赋形剂,如蔗糖,木糖,甘露醇,麦芽糖醇,麦芽醇,氯化钠,氧化铁黄,与司维拉姆混合的橙子香草香料和柠檬香料。
粉末制剂可以在合适数量的液体,如水中给病人施用,形成原位治疗制剂,并将治疗制剂对病人施用。治疗制剂可以是水-相治疗制剂或非-水制剂,优选地为水-相制剂,其中脂肪胺聚合物和阴离子稳定剂独立地熔解或悬浮。在给药之前,水-相治疗制剂可以通过在含有粉末制剂的容器中加入合适的水媒介,如水。在给药之前,非-水治疗制剂可以通过分散入合适的非-水媒介而获得,如杏仁油,花生油,大豆油,椰子油,橄榄油,罂粟-籽油,玉米油。可选地,发明的粉末制剂可以通过直接摄取注射给药。一单位剂量的粉末直接通过病人口并吞咽,合适地随同水或其他任何可吸收液体。可选地,发明的粉末制剂可以与食物混合对病人给药。
发明的粉末制剂可以用于治疗病人的高磷酸盐血症。病人中的高磷酸盐血症典型地定义为血清磷酸水平大于约4.5mg/dL。该状态,特别是存在较长时期时,导致演奏的钙和磷代谢异常并可以导致关节,肺和眼的异常石灰化。升高的血清磷水平通常在带有肾功能不全,甲状旁腺机能减退,假甲状旁腺机能减退,急性未治疗肢端肥大症,磷酸盐治疗过度,和当发生横纹肌溶解和治疗恶性肿瘤时的急性组织破坏。
这里使用的主体是哺乳动物,优选的为人类,但也可以是需要兽医治疗的动物,如宠物动物(如,狗,猫,和类似),农场动物(例如,奶牛,绵羊,猪,马,和类似)或实验动物(如, 大鼠,小鼠,豚鼠,和类似)。“需要治疗”的主体包括患有慢性肾功能不全的主体。其他需要治疗的主体的实施例包括患有磷酸代谢四条相关疾病的病人。该类型的疾病和/或失调的实施例包括甲状旁腺功能亢进,肾功能不全,高磷酸盐血症。
脂肪胺聚合物的“有效剂量”是与未治疗比较,用脂肪胺聚合物治疗的情况可获得良好的临床恢复的数量。对主体给药的脂肪胺聚合物的数量依赖于疾病或情况的程度,严重性,和类型,治疗设计的数量,和药物制剂的释放特点。其也依赖于主体的健康,大小,体重,年龄,性别和对药物的耐受性。典型地,发明的组合物对主体给药以在充分长的时期内获得期望的治疗效果。典型地为在每天5mg至15g脂肪胺聚合物(可选地为50mg每天至10g每天,可选地为1g每天至10g每天,可选地为1g每天至8g每天,可选地为2g每天至10g每天,可选地为41g每天至10g每天)对需要治疗的主体给药。这些剂量可以每天数次给药(例如,2,3,4,5次/天)或每天一次。脂肪胺聚合物可以与食物一起每天至少四次给药,与食物一起每天至少三次给药,与食物一起每天至少两次给药,与食物一起每天至少一次给药(见美国临时申请号60/623985,“磷酸结合物的每天一次制剂”2004,11月1日归档,其通过在此引述全部合并于本文。一个特别实施例,每天施用大约0.8-7.2g脂肪胺聚合物(例如,2-3次每天,2.4g或3.2g每剂量,或2-3次每天,4.0g或4.8g每剂量,或每天一次,7.2g每剂量)。
典型地,可以在进餐之前或之后,或在进餐中施用发明的制剂。这里使用的,进餐“之前”或“之后”典型地在2小时内,优选地在1小时内,跟优选地在30分钟内,最优选地在开始或结束进餐10分钟内。
发明的方法包括单独使用发明的粉末制剂时的单一-治疗。本发明的方法也包括与其他治疗活性药物的共-治疗。例如,本发明的方法可以与其他磷酸结合物联用,包括药学上可接受的镧,钙,铝,铁盐,如醋酸盐,碳酸盐,氧化物,氢氧化物,柠檬酸盐,藻酸盐,酮酸盐。钙盐,包括碳酸钙,醋酸钙(如PhosLo 醋酸钙片),柠檬酸钙,藻酸钙,酮酸钙,已经被用作磷酸结合物。摄取的钙与磷酸结合形成不溶性磷酸钙盐,如Ca3(PO4)2,CaHPO4,Ca(H2PO4)2。铝-基础的磷酸结合物,如Amphojel 氢氧化铝凝胶,已经用于治疗高磷酸盐血症。这些化合物与肠内的磷酸结合形成高度不溶的磷酸铝;结合的磷酸无法被病人吸收。最近铁和镧盐也已经使用。最近使用的镧盐,碳酸镧(Fosrenol)的特征类似于碳酸钙。
本领域中的普通技术人员知道根据本发明的方法对主体施用发明的多种成分的制剂数量将依赖于上述的因素。
发明通过以下实施例阐明,并不在任何方式上进行限定。
实施例
实施例1.发明的粉末制剂的组合物
通过标准药物制备技术生产粉末制剂,如描述于Remington’s药物科学,18th ed(1990),Mack出版公司,Easton,PA.发明的两种示范性粉末制剂(制剂A和B)的特定成分在下表1中显示。
成分 | 制剂A(wt%) | 制剂B(wt%) |
无水sevelemer HCl | 92.90 | |
无水sevelemer碳酸 | 94.97 | |
PGA | 1.00 | 3.00 |
橙子香草PR90 | 2.00 | 2.00 |
WG55香草 | 0.50 | 0.50 |
柠檬酸橙 | 0.11 | 0.12 |
NaCl | 1.00 | 1.00 |
三氯蔗糖 | 0.40 | 0.45 |
氧化铁黄 | 0.016 | 0.016 |
尽管本发明已经通过引述优选的实施方案而进行了特定的表示和描述,但是本领域的普通技术人员应当理解,在不脱离所附权利要求表示的范围的情况下,本发明在形式和细节上可以存在多种变化。
Claims (19)
1.一种粉末制剂,包括:
a)一种司维拉姆碳酸盐;和
b)一种藻酸丙二醇酯;
其中,在粉末中的唯一药物活性成分是司维拉姆碳酸盐。
2.根据权利要求1的粉末制剂,其中所述粉末进一步包括氯化钠。
3.根据权利要求2的粉末制剂,其中所述粉末进一步包括蔗糖。
4.根据权利要求3的粉末制剂,其中所述粉末进一步包括黄色的氧化铁。
5.根据权利要求4的粉末制剂,其中所述粉末进一步包括橙子香草PR90。
6.根据权利要求5的粉末制剂,其中粉末进一步包括WG55香草。
7.根据权利要求6的粉末制剂,其中所述粉末进一步包括一种柠檬酸橙。
8.根据权利要求7的粉末制剂,其中所述粉末被包装在一种容器中。
9.根据权利要求8的粉末制剂,其中所述容器是一种小袋。
10.根据权利要求9的粉末制剂,其中司维拉姆碳酸盐的量是以无水形式为基础的。
11.根据权利要求10的粉末制剂,其中所述粉末是未胶囊化的和自由流动的,并且包括粒度大于300微米的颗粒少于5wt%,粒度少于10微米的颗粒小于5wt%。
12.根据权利要求4的粉末制剂,其中所述粉末进一步包括柠檬香料。
13.根据权利要求12的粉末制剂,其中所述粉末被包装在一种容器中。
14.根据权利要求13的粉末制剂,其中所述容器是一种小袋。
15.根据权利要求14的粉末制剂,其中司维拉姆碳酸盐的量是以无水形式为基础的。
16.根据权利要求15的粉末制剂,其中粉末是未胶囊化的和自由流动的,并且包括粒度大于300微米的颗粒少于5wt%,粒度少于10微米的颗粒小于5wt%。
17.治疗有效量的权利要求1-7、10-12、15-16中任意一项所述的粉末制剂在制备用于治疗高磷酸盐血症的药物中的应用。
18.根据权利要求11所述的粉末制剂,其中,以无水形式为基础的司维拉姆碳酸盐的量是800mg。
19.根据权利要求11所述的粉末制剂,其中,以无水形式为基础的司维拉姆碳酸盐的量是2.4g。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210583520.0A CN103027896B (zh) | 2005-09-15 | 2006-09-12 | 胺聚合物的小袋制剂 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US71720005P | 2005-09-15 | 2005-09-15 | |
US60/717,200 | 2005-09-15 | ||
PCT/US2006/035370 WO2007035313A2 (en) | 2005-09-15 | 2006-09-12 | Sachet formulation for amine polymers |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210583520.0A Division CN103027896B (zh) | 2005-09-15 | 2006-09-12 | 胺聚合物的小袋制剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101272762A CN101272762A (zh) | 2008-09-24 |
CN101272762B true CN101272762B (zh) | 2013-02-06 |
Family
ID=37873217
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210583520.0A Active CN103027896B (zh) | 2005-09-15 | 2006-09-12 | 胺聚合物的小袋制剂 |
CN2006800340717A Active CN101272762B (zh) | 2005-09-15 | 2006-09-12 | 胺聚合物的小袋制剂 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210583520.0A Active CN103027896B (zh) | 2005-09-15 | 2006-09-12 | 胺聚合物的小袋制剂 |
Country Status (18)
Country | Link |
---|---|
US (4) | US9095509B2 (zh) |
EP (2) | EP1924246B1 (zh) |
JP (3) | JP5595660B2 (zh) |
KR (2) | KR101547925B1 (zh) |
CN (2) | CN103027896B (zh) |
AU (1) | AU2006292672B2 (zh) |
BR (1) | BRPI0616078B8 (zh) |
CA (1) | CA2622693C (zh) |
DK (1) | DK1924246T3 (zh) |
ES (1) | ES2556217T3 (zh) |
HK (2) | HK1111893A1 (zh) |
HU (1) | HUE026628T2 (zh) |
IL (3) | IL189967A (zh) |
NZ (1) | NZ566542A (zh) |
PL (1) | PL1924246T3 (zh) |
PT (1) | PT1924246E (zh) |
SI (1) | SI1924246T1 (zh) |
WO (1) | WO2007035313A2 (zh) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6733780B1 (en) | 1999-10-19 | 2004-05-11 | Genzyme Corporation | Direct compression polymer tablet core |
US7985418B2 (en) | 2004-11-01 | 2011-07-26 | Genzyme Corporation | Aliphatic amine polymer salts for tableting |
EP1951266A2 (en) * | 2005-09-02 | 2008-08-06 | Genzyme Corporation | Method for removing phosphate and polymer used therefore |
KR101547925B1 (ko) | 2005-09-15 | 2015-08-27 | 젠자임 코포레이션 | 아민 중합체에 대한 샤셋 제형 |
WO2007130463A2 (en) * | 2006-05-05 | 2007-11-15 | Genzyme Corporation | Amine condensation polymers as phosphate sequestrants |
WO2008011047A2 (en) * | 2006-07-18 | 2008-01-24 | Genzyme Corporation | Amine dendrimers |
EP2066293A2 (en) | 2006-09-29 | 2009-06-10 | Genzyme Corporation | Amide dendrimer compositions |
EP2120972A1 (en) | 2006-12-14 | 2009-11-25 | Genzyme Corporation | Amido-amine polymer compositions |
EP2114376A1 (en) * | 2007-02-23 | 2009-11-11 | Genzyme Corporation | Amine polymer compositions |
US20100196305A1 (en) * | 2007-03-08 | 2010-08-05 | Dhal Pradeep K | Sulfone polymer compositions |
JP2010525061A (ja) * | 2007-04-27 | 2010-07-22 | ゲンズイメ コーポレーション | アミドアミンデンドリマー組成物 |
EP2016947A1 (en) | 2007-07-17 | 2009-01-21 | Chemo Ibérica, S.A. | Novel one step process for preparing cross-linked poly(allylamine) polymers |
PA8807201A1 (es) * | 2007-12-14 | 2009-07-23 | Genzyme Corp | Composiciones farmaceuticas |
WO2009078958A1 (en) * | 2007-12-14 | 2009-06-25 | Genzyme Corporation | Coated pharmaceutical compositions |
WO2009154747A1 (en) * | 2008-06-20 | 2009-12-23 | Genzyme Corporation | Pharmaceutical compositions |
US8337824B2 (en) * | 2008-08-22 | 2012-12-25 | Relypsa, Inc. | Linear polyol stabilized polyfluoroacrylate compositions |
EP2441436A1 (de) | 2010-10-13 | 2012-04-18 | Fresenius Medical Care Deutschland GmbH | Phosphatbinderformulierung zur einfachen Einnahme |
WO2013064193A1 (en) | 2011-11-04 | 2013-05-10 | Synthon Bv | Pharmaceutical compositions comprising sevelamer |
CN102895204B (zh) * | 2012-11-08 | 2014-12-31 | 南京生命能科技开发有限公司 | 一种用于制备片剂的碳酸司维拉姆原料药及其制备方法和应用 |
CA2931547A1 (en) | 2013-12-09 | 2015-06-18 | Durect Corporation | Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same |
CN107412166B (zh) * | 2017-08-08 | 2020-03-24 | 同济大学 | 一种纳米复合吸附磷材料及其制备与应用 |
WO2020138921A1 (ko) * | 2018-12-24 | 2020-07-02 | 동인당제약 주식회사 | 세벨라머 함유 경구투여용 현탁제 조성물 및 그 제조방법 |
KR102281492B1 (ko) * | 2018-12-24 | 2021-07-26 | 동인당제약 주식회사 | 세벨라머 함유 경구투여용 현탁제 조성물 및 그 제조방법 |
JP7120695B1 (ja) | 2022-02-06 | 2022-08-17 | 豊光社テクノロジーズ株式会社 | 樹脂フィルム積層体とその製造方法、及び金属被覆樹脂の製造方法 |
WO2023149581A1 (ja) * | 2022-02-06 | 2023-08-10 | 豊光社テクノロジーズ株式会社 | 表面処理液、表面処理樹脂及び樹脂フィルム積層体の製造方法 |
EP4295836A1 (en) | 2022-06-22 | 2023-12-27 | Labomed Pharmaceutical Company S.A. | Sachet comprising a liquid suspension of a sevelamer salt |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4172120A (en) * | 1977-03-10 | 1979-10-23 | Reckitt & Colman Products Limited | Cholestyramine compositions and method for treating biliary gastritis |
US4439419A (en) * | 1980-02-20 | 1984-03-27 | The Upjohn Company | Method of treating gastric hyperacidity in humans employing a copolymer of polyethylenepolyamine and a bifunctional substance as epichlorhydrin |
US5496545A (en) * | 1993-08-11 | 1996-03-05 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
US5607669A (en) * | 1994-06-10 | 1997-03-04 | Geltex Pharmaceuticals, Inc. | Amine polymer sequestrant and method of cholesterol depletion |
WO2005065291A2 (en) * | 2003-12-31 | 2005-07-21 | Genzyme Corporation | Enteric coated aliphatic amine polymer bile acid sequestrants |
Family Cites Families (208)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2426125A (en) * | 1944-04-03 | 1947-08-19 | Kelco Co | Manufacture of glycol alginates |
US2456428A (en) * | 1944-10-11 | 1948-12-14 | Shell Dev | Polyallyl amine and related polymeric amines |
US2463824A (en) * | 1947-08-02 | 1949-03-08 | Kelco Co | Substituted alkylene glycol esters of alginic acid |
BE580490A (fr) | 1958-07-15 | 1960-01-08 | Merck & Co Inc | Compositions et procédés pour abaisser la teneur en cholestérol du sang |
US3104205A (en) * | 1959-12-17 | 1963-09-17 | Warner Lambert Pharmaceutical | Deodorant composition comprising the copper complex of the copolymer of allylamine and methacrylic acid |
US3308020A (en) * | 1961-09-22 | 1967-03-07 | Merck & Co Inc | Compositions and method for binding bile acids in vivo including hypocholesteremics |
US3332841A (en) * | 1961-10-04 | 1967-07-25 | Lilly Co Eli | Method of treating hyperacidity |
US3142621A (en) | 1961-11-02 | 1964-07-28 | Ciba Geigy Corp | Alginate suspensions of oral pharmaceutical compositions with improved taste qualities |
US3383236A (en) | 1964-04-17 | 1968-05-14 | Merck & Co Inc | Continuous pharmaceutical film coating process |
US3624209A (en) * | 1966-12-28 | 1971-11-30 | Bristol Myers Co | Composition for treatment of gastro-intestinal disorders |
GB1181003A (en) | 1967-03-20 | 1970-02-11 | Mead Johnson & Co | Therapeutic Compositions |
US3431138A (en) | 1967-07-14 | 1969-03-04 | American Cyanamid Co | Method for coating pharmaceutical forms with methyl cellulose |
US3539380A (en) | 1968-01-08 | 1970-11-10 | Upjohn Co | Methylcellulose and polyalkylene glycol coating of solid medicinal dosage forms |
DE1927336A1 (de) | 1968-06-17 | 1969-12-18 | Upjohn Co | Orale Dosierungsform zur Bekaempfung von Hypercholesterinaemie |
US3980770A (en) * | 1971-06-04 | 1976-09-14 | Pharmacia Aktiebolag | Polymerization products containing amino groups useful in serum cholesterol level control |
CH604722A5 (zh) | 1973-02-09 | 1978-09-15 | Sandoz Ag | |
AR206115A1 (es) | 1973-06-11 | 1976-06-30 | Merck & Co Inc | Procedimiento para preparar un polimero lineal no ramificado y no reticulado |
US4205064A (en) * | 1973-06-11 | 1980-05-27 | Merck & Co., Inc. | Bile acid sequestering composition containing poly[{alkyl-(3-ammoniopropyl)imino}-trimethylenedihalides] |
US4016209A (en) | 1975-04-23 | 1977-04-05 | Merck & Co., Inc. | 3-[N'-(3-Halopropyl)-N-'-methylamino]-N,N,N-trimethyl-1-propanaminium halide and acid addition salts thereof |
US4181718A (en) * | 1975-12-29 | 1980-01-01 | Mason Norbert S | Polyanion-stabilized aluminum hydrogels |
US4071478A (en) * | 1976-06-07 | 1978-01-31 | Merck & Co., Inc. | Controlled partially cross-linked 3,3-ionenes |
US4115537A (en) | 1976-09-07 | 1978-09-19 | American Hospital Supply Corporation | Resin tablet and use thereof in diagnostic tests |
US4183918A (en) * | 1977-03-08 | 1980-01-15 | Exxon Research & Engineering Co. | Detoxifying-medicinal emulsions |
GB1573487A (en) | 1977-05-23 | 1980-08-28 | Bristol Myers Co | Bile acid binding composition |
US4211763A (en) | 1977-08-08 | 1980-07-08 | The Dow Chemical Company | Anion exchange resin in the determination of thyroid function |
US4143130A (en) * | 1977-08-29 | 1979-03-06 | Warren-Teed Laboratories, Inc. | Method for treating kidney stones |
JPS5566513A (en) | 1978-11-14 | 1980-05-20 | Ono Pharmaceut Co Ltd | Drug for arteriosclerosis comprising high polymer compound as active constituent |
US4341563A (en) | 1978-11-17 | 1982-07-27 | Sankyo Company Limited | Protective coating compositions |
US4247393A (en) * | 1979-01-11 | 1981-01-27 | Wallace Richard A | Hemodialysis assist device |
US4264573A (en) | 1979-05-21 | 1981-04-28 | Rowell Laboratories, Inc. | Pharmaceutical formulation for slow release via controlled surface erosion |
US4543370A (en) | 1979-11-29 | 1985-09-24 | Colorcon, Inc. | Dry edible film coating composition, method and coating form |
US4302440B1 (en) | 1980-07-31 | 1986-08-05 | Easily-swallowed, powder-free and gastric-disintegrable aspirin tablet thinly-coated with hydroxypropyl methylcellulose and aqueous spray-coating preparation thereof | |
US4344993A (en) * | 1980-09-02 | 1982-08-17 | The Dow Chemical Company | Perfluorocarbon-polymeric coatings having low critical surface tensions |
GB2090605B (en) | 1980-12-12 | 1984-09-05 | Smith & Nephew Ass | Polymer of diallyl ammonium monomers pharmaceutical compositions thereof |
JPS5879022A (ja) | 1981-11-04 | 1983-05-12 | Bitamin Kenkyusho:Kk | 第四級窒素原子を含有する新規な金属架橋高分子化合物、その製法及び該高分子化合物を有効成分とする高脂血症治療剤 |
US4504640A (en) * | 1982-05-19 | 1985-03-12 | Nitto Boseki Co., Ltd. | Process for producing monoallylamine polymer |
DE3573884D1 (en) | 1982-07-08 | 1989-11-30 | Leo Ab | Substained release tablets and method for preparation thereof |
US4518433A (en) * | 1982-11-08 | 1985-05-21 | Fmc Corporation | Enteric coating for pharmaceutical dosage forms |
US4507466A (en) | 1983-01-07 | 1985-03-26 | The Dow Chemical Corporation | Dense star polymers having core, core branches, terminal groups |
US4539198A (en) | 1983-07-07 | 1985-09-03 | Rowell Laboratories, Inc. | Solid pharmaceutical formulations for slow, zero order release via controlled surface erosion: expanded range |
JPS6090243A (ja) * | 1983-10-25 | 1985-05-21 | Nitto Boseki Co Ltd | 小球状モノアリルアミン橋かけ重合体の製造方法 |
US4528347A (en) | 1983-11-10 | 1985-07-09 | 501 Nitto Boseki, Co. Ltd | Process for producing polymers of monoallylamine |
JPS60152424A (ja) | 1984-01-18 | 1985-08-10 | Daicel Chem Ind Ltd | 固形製剤 |
OA08092A (fr) | 1984-05-11 | 1987-03-31 | Bristol Myers Co | Novel bile sequestrant resin and uses. |
US4688988A (en) | 1984-12-17 | 1987-08-25 | United Technologies Corporation | Coolable stator assembly for a gas turbine engine |
US4631305A (en) * | 1985-03-22 | 1986-12-23 | The Upjohn Company | Polymeric material as a disintegrant in a compressed tablet |
DE3541511A1 (de) * | 1985-11-19 | 1987-05-21 | Grace W R Ab | Promoter fuer die papierleimung, verfahren zu dessen herstellung und dessen verwendung |
US4871779A (en) | 1985-12-23 | 1989-10-03 | The Dow Chemical Company | Ion exchange/chelation resins containing dense star polymers having ion exchange or chelate capabilities |
CH656535A5 (en) | 1986-01-24 | 1986-07-15 | Spirig Ag | Process for the production of stable pharmaceutical tablets which disintegrate rapidly in water |
JPS62132830U (zh) | 1986-02-18 | 1987-08-21 | ||
US4849227A (en) | 1986-03-21 | 1989-07-18 | Eurasiam Laboratories, Inc. | Pharmaceutical compositions |
IT1190349B (it) | 1986-06-16 | 1988-02-16 | Prodotti Formenti Srl | Composizioni farmaceutiche ad attivita' sequestrante degli acidi biliari contenenti colestiramina quale principio attivo,e procedimento per prepararle |
US5310572A (en) | 1987-02-03 | 1994-05-10 | Dow Corning Corporation | Process for forming a coated active agent-containing article |
US4762524A (en) | 1987-02-05 | 1988-08-09 | Hoechst Celanese Corporation | Composition comprising the addition product of a vinyl-sulfone dye and a secondary amine and process for dyeing a polyamide therewith |
US5073380A (en) | 1987-07-27 | 1991-12-17 | Mcneil-Ppc, Inc. | Oral sustained release pharmaceutical formulation and process |
US4983398A (en) | 1987-12-21 | 1991-01-08 | Forest Laboratories, Inc. | Sustained release drug dosage forms containing hydroxypropylmethylcellulose and alkali metal carboxylates |
US4853437A (en) * | 1988-03-04 | 1989-08-01 | Hercules Incorporated | Water- and caustic-insoluble, inswellable, fibrous, particulate crosslinked polymer |
US5520932A (en) | 1988-06-24 | 1996-05-28 | The Upjohn Company | Fine-milled colestipol hydrochloride |
AU628389B2 (en) | 1988-08-26 | 1992-09-17 | Pharmacia & Upjohn Company | Fine-beaded colestipol hydrochloride |
US5807582A (en) | 1988-08-26 | 1998-09-15 | Pharmacia & Upjohn Company | Fine-beaded colestipol hydrochloride and pharmaceutically elegant dosage forms made therefrom |
US5194464A (en) | 1988-09-27 | 1993-03-16 | Takeda Chemical Industries, Ltd. | Enteric film and preparatoin thereof |
GB8829835D0 (en) | 1988-12-21 | 1989-02-15 | Smith Kline French Lab | Compounds |
DE3901527A1 (de) | 1989-01-20 | 1990-07-26 | Hoechst Ag | Alkylierte polyethyleniminderivate, verfahren zu ihrer herstellung, ihre verwendung als arzneimittel sowie pharmazeutische praeparate |
US4956182A (en) | 1989-03-16 | 1990-09-11 | Bristol-Myers Company | Direct compression cholestyramine tablet and solvent-free coating therefor |
US5372823A (en) | 1989-03-16 | 1994-12-13 | Bristol-Myers Squibb Company | Direct compression cholestyramine tablet and solvent-free coating thereof |
US6274713B1 (en) * | 1989-04-07 | 2001-08-14 | Salutar, Inc. | Polychelants |
US5236701A (en) * | 1989-07-19 | 1993-08-17 | Lowchol Scientific Inc. | Ingestible hydrophilic polymeric amines useful for lowering blood cholesterol |
US4983399A (en) | 1989-10-18 | 1991-01-08 | Eastman Kodak Company | Direct compression carrier composition |
US5053423A (en) * | 1990-03-22 | 1991-10-01 | Quadra Logic Technologies Inc. | Compositions for photodynamic therapy |
JPH0687974B2 (ja) | 1990-03-27 | 1994-11-09 | 忠一 平山 | 発熱物質の吸着材料 |
DE4010271A1 (de) | 1990-03-30 | 1991-10-02 | Basf Ag | Verfahren zur herstellung von ethylenpolymerisaten bei druecken oberhalb von 500 bar in einem rohrreaktor mit einspritzfinger |
IE914179A1 (en) * | 1990-12-07 | 1992-06-17 | Ici Plc | Nitrogen derivatives |
US5262167A (en) | 1990-12-20 | 1993-11-16 | Basf Corporation | Edible, non-baked low moisture cholestyramine composition |
US5055197A (en) * | 1991-04-05 | 1991-10-08 | Rohm And Haas Company | Process for removing residual monomers and oligemers from amine-containing polymers |
US5108767A (en) * | 1991-06-10 | 1992-04-28 | Abbott Laboratories | Liquid nutritional product for persons receiving renal dialysis |
DE69227773T2 (de) | 1991-07-03 | 1999-05-20 | Upjohn Co | Tabletten mit hohem gehalt an colestipolhydrochlorid |
US5840339A (en) | 1991-07-30 | 1998-11-24 | Kunin; Robert | Blood cholesterol reducing pharmaceutical composition |
JP2785529B2 (ja) | 1991-08-21 | 1998-08-13 | 日東紡績株式会社 | エタノール徐放剤およびそれを用いた食品保存用組成物 |
EP0534304A1 (de) | 1991-09-21 | 1993-03-31 | Hoechst Aktiengesellschaft | Cycloalkylierte Polyethyleniminderivate und ihre Verwendung als Hypolipidämika |
SE470006B (sv) | 1991-09-26 | 1993-10-25 | Corline Systems Ab | Nytt konjugat, dess framställning och användning samt substrat preparerat med konjugatet |
JPH05170845A (ja) | 1991-12-20 | 1993-07-09 | Nippon Paint Co Ltd | 有機ポリマー微粒子およびその製法 |
US5610268A (en) | 1992-01-13 | 1997-03-11 | Dsm N.V. | Dendritic macromolecule and the preparation thereof |
US5530092A (en) | 1992-01-13 | 1996-06-25 | Dsm N.V. | Dendritic macromolecule and the preparation thereof |
US5654003A (en) | 1992-03-05 | 1997-08-05 | Fuisz Technologies Ltd. | Process and apparatus for making tablets and tablets made therefrom |
ES2110543T3 (es) * | 1992-07-22 | 1998-02-16 | Hoechst Ag | Derivados de poli(vinil-aminas) que tienen centros hidrofilos, procedimiento para su preparacion asi como la utilizacion de los compuestos como medicamentos, vehiculos de sustancias activas e ingredientes auxiliares para alimentos. |
ATE146193T1 (de) * | 1992-07-22 | 1996-12-15 | Hoechst Ag | Vernetzte, stickstoffhaltige vinylcopolymere, verfahren zu ihrer herstellung sowie die verwendung dieser verbindungen |
PL307527A1 (en) | 1992-08-20 | 1995-05-29 | Du Pont | Crosslinked polymeric ammonium salts |
US5302531A (en) * | 1992-10-22 | 1994-04-12 | Miles Inc. | Composition for the semiquantitative determination of specific gravity of a test sample |
DE69330595T2 (de) | 1992-11-25 | 2002-05-23 | Ajinomoto Kk | Zubereitungen und Nahrungsmittel enthaltend Mineralien und Poly-gamma-Glutaminsäure |
CA2153151A1 (en) | 1993-02-17 | 1994-09-01 | Robert Charles Hider | Polymeric compounds |
US5376396A (en) * | 1993-04-27 | 1994-12-27 | Merck & Co., Inc. | Beverage stabilizing system and process thereof |
JPH06321786A (ja) | 1993-05-12 | 1994-11-22 | Sekisui Chem Co Ltd | 胆汁酸腸管吸収抑制剤 |
US5487888A (en) | 1993-05-20 | 1996-01-30 | Geltex, Inc. | Iron-binding polymers for oral administration |
US5900475A (en) | 1994-06-10 | 1999-05-04 | Geltex Pharmaceuticals, Inc. | Hydrophobic sequestrant for cholesterol depletion |
US5703188A (en) | 1993-06-02 | 1997-12-30 | Geltex Pharmaceuticals, Inc. | Process for removing bile salts from a patient and compositions therefor |
AU7047994A (en) | 1993-06-02 | 1994-12-20 | Geltex Pharmaceuticals, Inc. | Compositions and process for removing bile salts |
US5618530A (en) | 1994-06-10 | 1997-04-08 | Geltex Pharmaceuticals, Inc. | Hydrophobic amine polymer sequestrant and method of cholesterol depletion |
US5624963A (en) | 1993-06-02 | 1997-04-29 | Geltex Pharmaceuticals, Inc. | Process for removing bile salts from a patient and compositions therefor |
CA2129079C (en) | 1993-08-03 | 2006-01-17 | Tatsuo Nomura | Orally administrable cholesterol lowering agent |
US5667775A (en) * | 1993-08-11 | 1997-09-16 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
ATE162958T1 (de) | 1993-11-25 | 1998-02-15 | Salternate B V | Teilchen zum binden monovalenten kationen und ihre verwendung |
US5414068A (en) * | 1994-01-24 | 1995-05-09 | Rohm And Haas Company | Crosslinked anion exchange particles and method for producing the particles |
TW474813B (en) | 1994-06-10 | 2002-02-01 | Geltex Pharma Inc | Alkylated composition for removing bile salts from a patient |
AUPM623994A0 (en) | 1994-06-15 | 1994-07-07 | Biomolecular Research Institute Limited | Antiviral dendrimers |
JP3355593B2 (ja) | 1994-08-19 | 2002-12-09 | 信越化学工業株式会社 | 固形腸溶製剤の製造方法 |
WO1996021454A1 (en) | 1995-01-12 | 1996-07-18 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
GB9503061D0 (en) | 1995-02-16 | 1995-04-05 | British Tech Group | Polymeric compounds |
JP2936129B2 (ja) | 1995-04-12 | 1999-08-23 | セイコー精機株式会社 | 防食構造 |
US5686106A (en) | 1995-05-17 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form for colonic delivery |
US5561214A (en) | 1995-05-18 | 1996-10-01 | Bayer Corporation | Hyperbranched polyaspartate esters and a process for their preparation |
US5709880A (en) | 1995-07-10 | 1998-01-20 | Buckman Laboratories International, Inc. | Method of making tabletized ionene polymers |
TW438608B (en) | 1995-08-02 | 2001-06-07 | Hisamitsu Pharmaceutical Co | A tablet containing anion exchange resin |
GB2308363A (en) | 1995-12-22 | 1997-06-25 | Courtaulds Coatings | Dendritic Polymers |
FI104823B (fi) | 1996-06-24 | 2000-04-14 | Borealis Polymers Oy | Likaantumista estävä päällyste |
US6034129A (en) | 1996-06-24 | 2000-03-07 | Geltex Pharmaceuticals, Inc. | Ionic polymers as anti-infective agents |
US5747067A (en) | 1996-12-06 | 1998-05-05 | Fmc Corporation | Co-processed products |
DE19654179A1 (de) | 1996-12-23 | 1998-06-25 | Basf Ag | H-förmige Polyamide |
US6203785B1 (en) | 1996-12-30 | 2001-03-20 | Geltex Pharmaceuticals, Inc. | Poly(diallylamine)-based bile acid sequestrants |
WO1998042355A1 (en) | 1997-03-25 | 1998-10-01 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers combined with a calcium supplement for oral administration |
US5925379A (en) | 1997-03-27 | 1999-07-20 | Geltex Pharmaceuticals, Inc. | Interpenetrating polymer networks for sequestration of bile acids |
TW592727B (en) | 1997-04-04 | 2004-06-21 | Chugai Pharmaceutical Co Ltd | Phosphate-binding polymer preparations |
JP3389493B2 (ja) | 1997-04-04 | 2003-03-24 | 中外製薬株式会社 | リン酸結合性ポリマー製剤 |
JPH10316576A (ja) | 1997-05-13 | 1998-12-02 | Nissui Pharm Co Ltd | キトサン含有錠剤 |
US6423754B1 (en) | 1997-06-18 | 2002-07-23 | Geltex Pharmaceuticals, Inc. | Method for treating hypercholesterolemia with polyallylamine polymers |
US6730735B2 (en) * | 1997-07-03 | 2004-05-04 | West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited | Conjugate of polyethylene glycol and chitosan |
WO1999004758A1 (en) | 1997-07-25 | 1999-02-04 | Elan Corporation Plc | A process for the preparation of a granulate suitable to the preparation of rapidly disintegrable mouth-soluble tablets |
US6187897B1 (en) | 1997-09-01 | 2001-02-13 | Toyo Ink Manufacturing Co., Ltd. | Vinyl-group-containing dendrimer and curable composition |
US6290947B1 (en) | 1997-09-19 | 2001-09-18 | Geltex Pharmaceuticals, Inc. | Ionic polymers as toxin-binding agents |
US6083497A (en) | 1997-11-05 | 2000-07-04 | Geltex Pharmaceuticals, Inc. | Method for treating hypercholesterolemia with unsubstituted polydiallylamine polymers |
US6566407B2 (en) * | 1997-11-05 | 2003-05-20 | Geltex Pharmaceuticals, Inc. | Method for reducing oxalate |
US5985938A (en) * | 1997-11-05 | 1999-11-16 | Geltex Pharmaceuticals, Inc. | Method for reducing oxalate |
US6726905B1 (en) | 1997-11-05 | 2004-04-27 | Genzyme Corporation | Poly (diallylamines)-based phosphate binders |
US6264937B1 (en) | 1998-01-09 | 2001-07-24 | Geltex Pharmaceuticals, Inc. | Fat-binding polymers |
US6090411A (en) | 1998-03-09 | 2000-07-18 | Temple University | Monolithic tablet for controlled drug release |
DE19835467A1 (de) * | 1998-08-06 | 2000-02-17 | Elenac Gmbh | Feststoffreaktor mit antistatischer Beschichtung zur Durchführung von Reaktionen in der Gasphase |
US6099862A (en) | 1998-08-31 | 2000-08-08 | Andrx Corporation | Oral dosage form for the controlled release of a biguanide and sulfonylurea |
TW568788B (en) | 1998-10-12 | 2004-01-01 | Chugai Pharmaceutical Co Ltd | Polymer combining with phosphoric acid and preparation containing the same |
JP2000178182A (ja) | 1998-12-17 | 2000-06-27 | Lion Corp | 崩壊性組成物 |
JP2001072576A (ja) | 1999-09-03 | 2001-03-21 | Kissei Pharmaceut Co Ltd | 経口用医薬品組成物 |
US6362266B1 (en) | 1999-09-03 | 2002-03-26 | The Dow Chemical Company | Process for reducing cohesiveness of polyallylamine polymer gels during drying |
US6180754B1 (en) | 1999-09-03 | 2001-01-30 | The Dow Chemical Company | Process for producing cross-linked polyallylamine polymer |
WO2001022941A1 (en) | 1999-09-28 | 2001-04-05 | H. Lundbeck A/S | Melt granulated composition and modified release dosage form prepared from said composition |
AU778262B2 (en) * | 1999-10-19 | 2004-11-25 | Genzyme Corporation | Direct compression polymer tablet core |
US20020054903A1 (en) | 1999-10-19 | 2002-05-09 | Joseph Tyler | Direct compression polymer tablet core |
US6733780B1 (en) | 1999-10-19 | 2004-05-11 | Genzyme Corporation | Direct compression polymer tablet core |
WO2001066607A1 (fr) | 2000-03-09 | 2001-09-13 | Hisamitsu Pharmaceutical Co., Inc. | Resine echangeuse d'anions reticulee ou sel de celle-ci et adsorbant phosphoreux la contenant |
US20030091530A1 (en) | 2000-03-13 | 2003-05-15 | Takeshi Goto | Preventives and/or remedies for hyperphosphatemia |
DE60110232T2 (de) * | 2000-07-28 | 2006-01-19 | F. Hoffmann-La Roche Ag | Neue verwendung von lipase-inhibitoren |
US6908609B2 (en) | 2000-11-20 | 2005-06-21 | Dow Global Technologies Inc. | In vivo use of water absorbent polymers |
US20030175349A1 (en) | 2001-01-30 | 2003-09-18 | Council Of Scientific And Industrial Research | Pharmaceutical compostion for extended/sustained release of a therapeutically active ingredient |
US6534600B2 (en) | 2001-03-26 | 2003-03-18 | Michigan Molecular Institute | Hyperbranched polyureas, polyurethanes, polyamidoamines, polyamides and polyesters |
MXPA03009568A (es) | 2001-04-18 | 2004-02-12 | Genzyme Corp | Metodo para reducir el nivel de glucosa en el suero. |
WO2002085379A1 (en) | 2001-04-18 | 2002-10-31 | Geltex Pharmaceuticals, Inc. | Method for improving vascular access in patients with vascular shunts |
CA2444347A1 (en) | 2001-04-18 | 2002-10-31 | Genzyme Corporation | Method for treating gout and binding uric acid |
WO2002085380A1 (en) | 2001-04-18 | 2002-10-31 | Geltex Pharmaceuticals, Inc. | Method for treating gout and reducing serum uric acid |
KR20040018359A (ko) | 2001-04-18 | 2004-03-03 | 젠자임 코포레이션 | 지방족 폴리아민으로 x 증후군을 치료하는 방법 |
KR20040018357A (ko) | 2001-04-18 | 2004-03-03 | 젠자임 코포레이션 | 저염 형태의 폴리알릴아민 |
WO2002085383A1 (en) | 2001-04-18 | 2002-10-31 | Genzyme Corporation | Method for reducing copper levels and treating copper toxicosis |
AU2002303148A1 (en) * | 2001-06-29 | 2003-03-03 | Leon J. Lewandowski | Individualized addiction cessation therapy |
US7879869B2 (en) | 2001-07-30 | 2011-02-01 | Mitsubishi Tanabe Pharma Corporation | Drugs for ameliorating postcibal hyperglycemia |
US6600011B2 (en) | 2001-10-09 | 2003-07-29 | Genzyme Corporation | Process for purification and drying of polymer hydrogels |
US7815936B2 (en) | 2001-10-30 | 2010-10-19 | Evonik Degussa Gmbh | Use of granular materials based on pyrogenically produced silicon dioxide in pharmaceutical compositions |
DE10163163A1 (de) | 2001-12-20 | 2003-07-03 | Basf Ag | Verfahren zur Herstellung hochfunktioneller, Hyperverzweigter Polyester durch enzymatische Veresterung |
US7208314B2 (en) | 2002-02-26 | 2007-04-24 | Mirus Bio Corporation | Compositions and methods for drug delivery using pH sensitive molecules |
US20030161875A1 (en) * | 2002-02-27 | 2003-08-28 | Deepak Murpani | Fast dissolving tablets of cyclooxygenase-2 enzyme inhibitors |
US7109184B2 (en) * | 2002-03-19 | 2006-09-19 | Genzyme Corporation | Phosphate transport inhibitors |
US20030180250A1 (en) | 2002-03-22 | 2003-09-25 | Council Of Scientific And Industrial Research | Compositions and complexes containing a macromolecular compound as potential anti-inflammatory agents |
US7169450B2 (en) * | 2002-05-15 | 2007-01-30 | Mcneil-Ppc, Inc. | Enrobed core |
US20040161474A1 (en) | 2002-05-24 | 2004-08-19 | Moerck Rudi E. | Rare earth metal compounds methods of making, and methods of using the same |
ITMI20021718A1 (it) | 2002-07-31 | 2004-02-01 | Sematic Italia Spa | Interruttore di sicurezza con sistema elettronico programmabile. |
GB0218781D0 (en) | 2002-08-13 | 2002-09-18 | Astrazeneca Ab | Chemical process |
US7220406B2 (en) * | 2002-10-22 | 2007-05-22 | Genzyme Corporation | Method for promoting bone formation |
DE10250711A1 (de) | 2002-10-31 | 2004-05-19 | Degussa Ag | Pharmazeutische und kosmetische Zubereitungen |
US9107804B2 (en) | 2002-12-10 | 2015-08-18 | Nortec Development Associates, Inc. | Method of preparing biologically active formulations |
WO2004099288A1 (en) | 2003-05-09 | 2004-11-18 | Carlsberg A/S | Polyethyleneimine polymers |
TW200507882A (en) | 2003-07-17 | 2005-03-01 | Kyowa Hakko Kogyo Kk | Solid formulations |
WO2005021000A1 (en) | 2003-08-28 | 2005-03-10 | Ranbaxy Laboratories Limited | Solid oral dosage forms of gatifloxacin |
US7385012B2 (en) | 2003-11-03 | 2008-06-10 | Ilypsa, Inc. | Polyamine polymers |
US7459502B2 (en) * | 2003-11-03 | 2008-12-02 | Ilypsa, Inc. | Pharmaceutical compositions comprising crosslinked polyamine polymers |
US7608674B2 (en) | 2003-11-03 | 2009-10-27 | Ilypsa, Inc. | Pharmaceutical compositions comprising cross-linked small molecule amine polymers |
US7335795B2 (en) | 2004-03-22 | 2008-02-26 | Ilypsa, Inc. | Crosslinked amine polymers |
US7449605B2 (en) | 2003-11-03 | 2008-11-11 | Ilypsa, Inc. | Crosslinked amine polymers |
US7767768B2 (en) | 2003-11-03 | 2010-08-03 | Ilypsa, Inc. | Crosslinked amine polymers |
US20050208095A1 (en) | 2003-11-20 | 2005-09-22 | Angiotech International Ag | Polymer compositions and methods for their use |
US7309500B2 (en) | 2003-12-04 | 2007-12-18 | The Board Of Trustees Of The University Of Illinois | Microparticles |
WO2005072752A1 (ja) * | 2004-01-30 | 2005-08-11 | Taisho Pharmaceutical Co., Ltd. | 高リン血症の予防又は治療剤 |
US8192758B2 (en) | 2004-03-30 | 2012-06-05 | Relypsa, Inc. | Ion binding compositions |
US7556799B2 (en) | 2004-03-30 | 2009-07-07 | Relypsa, Inc. | Ion binding polymers and uses thereof |
US7429394B2 (en) | 2004-03-30 | 2008-09-30 | Relypsa, Inc. | Ion binding compositions |
US8282960B2 (en) | 2004-03-30 | 2012-10-09 | Relypsa, Inc. | Ion binding compositions |
KR20050104152A (ko) | 2004-04-28 | 2005-11-02 | 최승호 | 경구용 약물의 흡수를 증진하는 약제학적 조성물 |
DK1758557T3 (da) * | 2004-05-11 | 2011-10-24 | Egalet Ltd | Kvældbar doseringsform omfattende gellangummi |
US7973122B2 (en) | 2004-06-17 | 2011-07-05 | General Cable Technologies Corporation | Polyamideimide compositions having multifunctional core structures |
JP4845353B2 (ja) * | 2004-06-29 | 2011-12-28 | 田辺三菱製薬株式会社 | 陰イオン交換樹脂を含む医薬組成物 |
US20060024368A1 (en) | 2004-07-30 | 2006-02-02 | Reza Fassihi | Compressed composite delivery system for release-rate modulation of bioactives |
US7218130B2 (en) | 2004-08-25 | 2007-05-15 | Micron Technology, Inc. | Bottom side stiffener probe card |
US7019085B2 (en) | 2004-08-30 | 2006-03-28 | Albright Robert L | Phosphate selective resin and related methods |
TWM271254U (en) | 2004-09-10 | 2005-07-21 | Sen Tech Co Ltd | Heat dissipation base and package structure for light-emitting diode |
CA2583548A1 (en) | 2004-10-15 | 2006-04-27 | Altairnano, Inc. | Phosphate binder with reduced pill burden |
US20060177415A1 (en) | 2004-11-01 | 2006-08-10 | Burke Steven K | Once a day formulation for phosphate binders |
US7985418B2 (en) | 2004-11-01 | 2011-07-26 | Genzyme Corporation | Aliphatic amine polymer salts for tableting |
WO2006072054A1 (en) | 2004-12-30 | 2006-07-06 | Genzyme Corporation | Zinc-containing treatments for hyperphosphatemia |
CA2601236A1 (en) | 2005-03-16 | 2006-09-21 | Usv Limited | An improved process for the preparation of crosslinked polyallylamine polymer |
DE102005037632A1 (de) | 2005-08-09 | 2007-02-15 | Hilti Ag | Wanddetektor |
EP1924256A1 (en) | 2005-09-14 | 2008-05-28 | Wisconsin Alumni Research Foundation | Composition comprising a dendrimer and the use thereof for binding phosphate |
KR101547925B1 (ko) | 2005-09-15 | 2015-08-27 | 젠자임 코포레이션 | 아민 중합체에 대한 샤셋 제형 |
US20070094779A1 (en) | 2005-10-31 | 2007-05-03 | Dauphin Joseph A | Three piece toilet maintenance kit |
US20070110707A1 (en) | 2005-11-04 | 2007-05-17 | Washington University | Method of treating diseases involving non-enzymatic glycation |
-
2006
- 2006-09-12 KR KR1020087008861A patent/KR101547925B1/ko active IP Right Grant
- 2006-09-12 KR KR1020147030653A patent/KR101574072B1/ko active IP Right Grant
- 2006-09-12 CN CN201210583520.0A patent/CN103027896B/zh active Active
- 2006-09-12 DK DK06824928.3T patent/DK1924246T3/en active
- 2006-09-12 CN CN2006800340717A patent/CN101272762B/zh active Active
- 2006-09-12 SI SI200631995T patent/SI1924246T1/sl unknown
- 2006-09-12 BR BRPI0616078A patent/BRPI0616078B8/pt active IP Right Grant
- 2006-09-12 WO PCT/US2006/035370 patent/WO2007035313A2/en active Application Filing
- 2006-09-12 EP EP06824928.3A patent/EP1924246B1/en active Active
- 2006-09-12 US US11/519,982 patent/US9095509B2/en active Active
- 2006-09-12 JP JP2008531228A patent/JP5595660B2/ja active Active
- 2006-09-12 PL PL06824928T patent/PL1924246T3/pl unknown
- 2006-09-12 HU HUE06824928A patent/HUE026628T2/en unknown
- 2006-09-12 EP EP15184007.1A patent/EP3000460A1/en not_active Withdrawn
- 2006-09-12 PT PT68249283T patent/PT1924246E/pt unknown
- 2006-09-12 NZ NZ566542A patent/NZ566542A/en unknown
- 2006-09-12 CA CA2622693A patent/CA2622693C/en not_active Expired - Fee Related
- 2006-09-12 ES ES06824928.3T patent/ES2556217T3/es active Active
- 2006-09-12 AU AU2006292672A patent/AU2006292672B2/en active Active
-
2008
- 2008-03-06 IL IL189967A patent/IL189967A/en active IP Right Grant
- 2008-06-14 HK HK08106583.2A patent/HK1111893A1/zh unknown
-
2014
- 2014-07-02 JP JP2014136594A patent/JP5922184B2/ja active Active
-
2015
- 2015-06-24 IL IL239617A patent/IL239617A/en active IP Right Grant
- 2015-06-25 US US14/750,459 patent/US9585911B2/en active Active
- 2015-12-25 JP JP2015254217A patent/JP6029736B2/ja active Active
-
2016
- 2016-09-26 HK HK16111262.0A patent/HK1223024A1/zh unknown
-
2017
- 2017-01-26 US US15/416,958 patent/US20170326172A1/en not_active Abandoned
- 2017-07-28 IL IL253711A patent/IL253711A0/en unknown
-
2018
- 2018-01-05 US US15/863,554 patent/US20180353536A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4172120A (en) * | 1977-03-10 | 1979-10-23 | Reckitt & Colman Products Limited | Cholestyramine compositions and method for treating biliary gastritis |
US4439419A (en) * | 1980-02-20 | 1984-03-27 | The Upjohn Company | Method of treating gastric hyperacidity in humans employing a copolymer of polyethylenepolyamine and a bifunctional substance as epichlorhydrin |
US5496545A (en) * | 1993-08-11 | 1996-03-05 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
US5607669A (en) * | 1994-06-10 | 1997-03-04 | Geltex Pharmaceuticals, Inc. | Amine polymer sequestrant and method of cholesterol depletion |
WO2005065291A2 (en) * | 2003-12-31 | 2005-07-21 | Genzyme Corporation | Enteric coated aliphatic amine polymer bile acid sequestrants |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101272762B (zh) | 胺聚合物的小袋制剂 | |
AU735260B2 (en) | Polyallylamine polymers for treating hypercholesterolemia | |
US20070286841A1 (en) | Method for lowering serum glucose | |
WO2006050314A2 (en) | Once a day formulation for phosphate binders | |
CN102824322A (zh) | 用作片剂的脂肪胺聚合物盐 | |
WO2002085380A1 (en) | Method for treating gout and reducing serum uric acid | |
US20020182168A1 (en) | Method for reducing copper levels and treating copper toxicosis | |
AU2012205214B2 (en) | Formulation for Amine Polymers | |
EP1923064A2 (en) | Use of amine polymer for lowering serum glucose |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant |