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1. 发明授权

US5955502A Use of fatty acid esters as bioadhesive substances 失效
标题翻译：使用脂肪酸酯作为生物粘附物质
公开(公告)号：US5955502A
公开(公告)日：1999-09-21
申请号：US829496
申请日：1997-03-27
申请人： Jens Hansen , Lise Sylvest Nielsen , Tomas Norling
发明人： Jens Hansen , Lise Sylvest Nielsen , Tomas Norling
IPC分类号： A61K9/00 , A61K9/127 , A61K9/50 , A61K47/14 , B82B1/00 , A61K38/00 , A61K39/395
CPC分类号： A61K9/0014 , A61K47/14 , A61K9/1274 , A61K9/5015 , A61K9/5078
摘要： Use of fatty acid esters as bioadhesive substances. The fatty acid esters have molecular weights below about 1000 dalton and the fatty acid component of the fatty acid ester is a saturated or unsaturated fatty acid having a total number of carbon atoms of from C.sub.8 to C.sub.22. Particularly suitable fatty acid esters for use according to the invention are fatty acid esters which are selected from the group consisting of fatty acid esters of polyhydric alcohols, fatty acid esters of hydroxycarboxylic acids, fatty acid esters of monosaccharides, fatty acid esters of glycerylphosphate derivatives, fatty acid esters of glycerylsulfate derivative, and mixtures thereof. Excellent bioadhesive properties have been observed for fatty acid esters are glyceryl monooleate, glyceryl monolinoleate or glyceryl monolinolenate.Methods are described for administering an active or protective substance to undamaged or damaged skin or mucosa of an animal such as a human by combining the active or protective substance with a bioadhesive fatty acid ester. The mucosa may be the oral, aural, nasal, lung, gastrointestinal, vaginal, or rectal mucosa. The administration may also be to body cavities such as the oral cavity, e.g. via buccal administration.
摘要翻译：使用脂肪酸酯作为生物粘附物质。脂肪酸酯的分子量低于约1000道尔顿，脂肪酸酯的脂肪酸组分是碳原子数为C8〜C22的饱和或不饱和脂肪酸。根据本发明使用的特别合适的脂肪酸酯是选自多元醇的脂肪酸酯，羟基羧酸的脂肪酸酯，单糖的脂肪酸酯，磷酸甘油酯衍生物的脂肪酸酯，甘油硫酸酯衍生物的脂肪酸酯及其混合物。已经观察到对于脂肪酸酯具有优异的生物粘合性质，是单油酸甘油酯，单烯醇甘油酯或甘油单苯三酸盐。描述了通过将活性或保护性物质与生物粘附性脂肪酸酯组合来将活性或保护性物质施用于动物如人的未损伤或损伤的皮肤或粘膜的方法。粘膜可以是口服，听觉，鼻，肺，胃肠道，阴道或直肠粘膜。给药也可以是体腔，例如口腔，例如。通过口腔管理。

2. 发明授权

US06228383B1 Use of fatty acid esters as bioadhesive substances 失效
标题翻译：使用脂肪酸酯作为生物粘附物质
公开(公告)号：US06228383B1
公开(公告)日：2001-05-08
申请号：US08462222
申请日：1995-06-05
申请人： Jens Hansen , Lise Sylvest Nielsen , Tomas Norling
发明人： Jens Hansen , Lise Sylvest Nielsen , Tomas Norling
IPC分类号： A61K3120
CPC分类号： A61K9/5078 , A61K9/1274 , A61K9/5015 , A61K47/14
摘要： Use of fatty acid esters as bioadhesive substances. The fatty acid esters have molecular weights below about 1000 dalton and the fatty acid component of the fatty acid ester is a saturated or unsaturated fatty acid having a total number of carbon atoms of from C8 to C22. Particularly suitable fatty acid esters for use according to the invention are fatty acid esters which are selected from the group consisting of fatty acid esters of polyhydric alcohols, fatty acid esters of hydroxycarboxylic acids, fatty acid esters of monosaccharides, fatty acid esters of glycerylphosphate derivatives, fatty acid esters of glycerylsulfate derivative, and mixtures thereof. Excellent bioadhesive properties have been observed for fatty acid esters are glyceryl monooleate, glyceryl monolinoleate or glyceryl monolinolenate. Methods are described for administering an active or protective substance to undamaged or damaged skin or mucosa of an animal such as a human by combining the active or protective substance with a bioadhesive fatty acid ester. The mucosa may be the oral, aural, nasal, lung, gastrointestinal, vaginal, or rectal mucosa. The administration may also be to body cavities such as the oral cavity, e.g. via buccal administration.
摘要翻译：使用脂肪酸酯作为生物粘附物质。脂肪酸酯的分子量低于约1000道尔顿，脂肪酸酯的脂肪酸组分是碳原子数为C8〜C22的饱和或不饱和脂肪酸。根据本发明使用的特别合适的脂肪酸酯是选自多元醇的脂肪酸酯，羟基羧酸的脂肪酸酯，单糖的脂肪酸酯，磷酸甘油酯衍生物的脂肪酸酯，甘油硫酸酯衍生物的脂肪酸酯及其混合物。已经观察到对于脂肪酸酯具有优异的生物粘合性质，是单油酸甘油酯，单烯醇甘油酯或甘油单苯三酸盐。描述了通过将活性或保护性物质与生物粘附性脂肪酸酯组合来将活性或保护性物质施用于动物如人的未损伤或损伤的皮肤或粘膜的方法。粘膜可以是口服，听觉，鼻，肺，胃肠道，阴道或直肠粘膜。给药也可以是体腔，例如口腔，例如。通过口腔管理。

3. 发明授权

US5958458A Pharmaceutical multiple unit particulate formulation in the form of coated cores 失效
标题翻译：以涂层芯的形式制备多单位颗粒制剂
公开(公告)号：US5958458A
公开(公告)日：1999-09-28
申请号：US509107
申请日：1995-08-01
申请人： Tomas Norling , Lone Norgaard Jensen , Jens Hansen
发明人： Tomas Norling , Lone Norgaard Jensen , Jens Hansen
IPC分类号： A61K9/00 , A61K9/16 , A61K9/20 , A61K9/46 , A61K9/50 , A61K47/02
CPC分类号： A61K9/2081 , A61K9/0007 , A61K9/1611 , A61K9/1676 , A61K9/5015 , A61K9/5026 , A61K9/5047 , A61K9/5078 , A61K9/0095 , Y10S514/951
摘要： A pharmaceutical multiple unit particulate formulation in the form of coated cores which includes a pharmaceutically acceptable carrier selected from calcium carbonate, calcium silicate, calcium magnesium silicate, calcium phosphate, kaolin, sodium hydrogen carbonate, sodium sulfate, barium carbonate, barium sulfate, magnesium sulfate, magnesium carbonate, and activated carbon, and an active substance in a layer on the outer surface of the cores.
摘要翻译：包衣核心形式的药物多单元颗粒制剂，其包括选自碳酸钙，硅酸钙，硅酸钙镁，磷酸钙，高岭土，碳酸氢钠，硫酸钠，碳酸钡，硫酸钡，硫酸镁的药学上可接受的载体，碳酸镁和活性炭，以及在芯的外表面上的层中的活性物质。

4. 发明授权

US09173847B2 Tablet comprising a fibrate 有权
标题翻译：片剂包含贝特类
公开(公告)号：US09173847B2
公开(公告)日：2015-11-03
申请号：US11449918
申请日：2006-06-09
申请人： Per Holm , Tomas Norling
发明人： Per Holm , Tomas Norling
IPC分类号： A61K9/20 , A61K9/16 , A61K31/192
CPC分类号： A61K9/2077 , A61K9/1623 , A61K31/192
摘要： Stable tablets and pharmaceutical compositions in particulate form comprising a fibrate, for example fenofibrate, dissolved or dispersed in an non-aqueous vehicle with improved bioavailability, thereby eliminating the food effect so that the tablet or composition can be administered to a patient irrespective of being in fed or fasted state.
摘要翻译：稳定的片剂和药物组合物，其包含溶解或分散在具有改善的生物利用度的非水性载体中的贝特类贝特类，例如非诺贝特，从而消除食物效应，使得片剂或组合物可以施用于患者，而不管喂食或禁食状态。

5. 发明申请

US20070014846A1 PHARMACEUTICAL COMPOSITIONS COMPRISING FENOFIBRATE AND ATORVASTATIN 审中-公开
标题翻译：包含芬太尼和ATORVASTATIN的药物组合物
公开(公告)号：US20070014846A1
公开(公告)日：2007-01-18
申请号：US11456566
申请日：2006-07-11
申请人： Per Holm , Tomas Norling
发明人： Per Holm , Tomas Norling
IPC分类号： A61K31/192 , A61K9/48
CPC分类号： A61K9/1676 , A61K9/1611 , A61K9/1617 , A61K9/1635 , A61K9/1641 , A61K9/1652 , A61K9/1682 , A61K9/2077 , A61K9/48 , A61K31/192
摘要： Pharmaceutical compositions in particulate form or in solid dosage forms comprising a combination of fenofibrate and the HMG CoA reductase inhibitor atorvastatin or a pharmaceutically active salt thereof, which upon oral administration provides a relative AUC0-24 value (AUCfibric acid/AUCatorvastatin) of between about 250 and about 10,000. The solid compositions are manufactured without any need of addition of water or aqueous medium. Atorvastatin is optionally provided as a controlled release or a delayed release formulation resulting in a maintained LDL-lowering effect at a reduced dosage, and fenofibrate is provided in a formulation having increasing bioavailability and reduced food effect.
摘要翻译：包含非诺贝特和HMG CoA还原酶抑制剂阿托伐他汀或其药物活性盐的组合的药物组合物，其在口服给药时提供相对AUC 0-24值（AUC 大约250至大约10,000之间的纤维酸/阿托伐他汀的AUC）。制造固体组合物，而不需要加入水或水性介质。任选地提供阿托伐他汀作为控制释放或延迟释放制剂，导致在减少的剂量下维持的LDL降低作用，并且在具有增加的生物利用度和降低的食物效应的制剂中提供非诺贝特。

6. 发明申请

US20060068015A1 Solid dosage form comprising a fibrate and a statin 审中-公开
标题翻译：包含贝特类和他汀类的固体剂型
公开(公告)号：US20060068015A1
公开(公告)日：2006-03-30
申请号：US10513778
申请日：2004-10-01
申请人： Per Holm , Tomas Norling
发明人： Per Holm , Tomas Norling
IPC分类号： A61K31/401 , A61K31/366 , A61K31/225 , A61K31/192
CPC分类号： A61K31/366 , A61K9/1611 , A61K9/1617 , A61K9/1623 , A61K9/1652 , A61K9/2013 , A61K9/2018 , A61K9/2077 , A61K31/192 , A61K31/195 , A61K31/216 , A61K31/22 , A61K31/40 , A61K31/505 , A61K45/06 , A61K2300/00
摘要： The present invention relates to pharmaceutical compositions in particulate form or in solid dosage forms comprising a combination of a fibrate, notably fenofibrate, and a statin (also known as a HMG CoA reductase inhibitors), which compositions are manufactured without any need of addition of water or an aqueous medium and wherein at least 80% of the active substances (i.e. the fibrate and the statin) are present in the composition in dissolved form in order to ensure suitable bioavailability of both active ingredients upon oral administration
摘要翻译：本发明涉及颗粒形式或固体剂型的药物组合物，其包含贝特类，特别是非诺贝特和他汀类（也称为HMG CoA还原酶抑制剂）的组合，该组合物在不需要添加水的情况下制造或水性介质，并且其中至少80％的活性物质（即贝特类和他汀类）以溶解形式存在于组合物中，以确保口服给药时两种活性成分的合适的生物利用度

7. 发明申请

US20050096390A1 Compositions comprising fenofibrate and pravastatin 审中-公开
标题翻译：包含非诺贝特和普伐他汀的组合物
公开(公告)号：US20050096390A1
公开(公告)日：2005-05-05
申请号：US10988818
申请日：2004-11-15
申请人： Per Holm , Tomas Norling
发明人： Per Holm , Tomas Norling
IPC分类号： A61K9/16 , A61K9/20 , A61K31/216 , A61K31/22 , A61K31/40 , A61K45/06 , A61K31/225 , A61K31/19
CPC分类号： A61K45/06 , A61K9/1611 , A61K9/1617 , A61K9/1623 , A61K9/1652 , A61K9/2013 , A61K9/2018 , A61K9/2027 , A61K9/2077 , A61K31/216 , A61K31/22 , A61K31/40 , A61K2300/00
摘要： The present invention relates to pharmaceutical compositions in particulate form or in solid dosage forms comprising a combination of fenofibrate and the HMG CoA reductase inhibitor pravastatin or a pharmaceutically active salt thereof, which upon oral administration provides a relative AUC0-24 value (AUCfibric acid/AUCpravastatin) of between about 90 and about 6300. The solid compositions are manufactured without any need of addition of water or aqueous medium and comprise at least 80% of the active substances fenofibrate and pravastatin in dissolved form, or, optionally, atorvastatin in micronized form, in order to ensure suitable bioavailability.
摘要翻译：本发明涉及颗粒形式的药物组合物或固体剂型，其包含非诺贝特和HMG CoA还原酶抑制剂普伐他汀或其药物活性盐的组合，其在口服给药时提供相对AUC 0-24 约90和约6300之间的值（AUC 纤维酸/ AUC 普伐他汀）。固体组合物在不需要添加水或水性介质的情况下制造，并且包括至少80％的非诺贝特活性物质和溶解形式的普伐他汀，或任选地以微粉化形式的阿伐他汀，以确保合适的生物利用度。

8. 发明授权

US5143934A Method and composition for controlled delivery of biologically active agents 失效
标题翻译：用于控制递送生物活性剂的方法和组合物
公开(公告)号：US5143934A
公开(公告)日：1992-09-01
申请号：US424416
申请日：1989-10-20
申请人： Pia Lading , Yvonne Lundsholm , Tomas Norling
发明人： Pia Lading , Yvonne Lundsholm , Tomas Norling
IPC分类号： A61K47/44 , A61K9/22 , A61K31/415 , A61K47/14 , A61K47/26 , A61P1/02
CPC分类号： A61K9/1274 , A61K9/0063 , Y10S514/943 , Y10S514/944 , Y10S514/964
摘要： Controlled delivery of biologically active agents such as pharmaceuticals to body sites is accomplished by combination with a monoglyceride and a vegetable oil. Upon contact with an aqueous liquid, the composition forms a reverse hexagonal liquid crystalline phase matrix which releases the active agent in controlled fashion. The method of delivery is particularly useful for the treatment of periodontal disease by insertion of the liquid crystalline phase precursor composition directly into the periodontal pocket, where water from the gingival fluid induces the spontaneous in situ formation of the reverse hexagonal liquid crystalline phase matrix.
摘要翻译：通过与单酸甘油酯和植物油的组合来实现对生物活性剂如药物到体内部位的控制递送。当与水性液体接触时，组合物形成反向六方晶系液晶相，其以受控的方式释放活性剂。递送方法对于通过将液晶相前体组合物直接插入到牙周袋中来治疗牙周病特别有用，其中来自牙龈流体的水诱导反向六边形液晶相基质的自发原位形成。

9. 发明授权

US08664239B2 Tacrolimus for improved treatment of transplant patients 有权
公开(公告)号：US08664239B2
公开(公告)日：2014-03-04
申请号：US13167420
申请日：2011-06-23
申请人： Robert D. Gordon , Per Holm , Anne-Marie Lademann , Tomas Norling
发明人： Robert D. Gordon , Per Holm , Anne-Marie Lademann , Tomas Norling
IPC分类号： A61K31/44 , A61K31/436
CPC分类号： A61K31/436 , A61K9/0053 , A61K9/1617 , A61K9/1641 , A61K9/1652 , A61K9/2013 , A61K9/2027 , A61K9/2031 , A61K9/2054 , A61K9/2077 , A61K9/284 , A61K9/2846 , A61K9/4891 , A61K47/10 , Y10S514/885
摘要： An extended release oral dosage form comprising as active substance tacrolimus or a pharmaceutically active analogue thereof for a once daily immunosuppressive treatment of a patient in need thereof, preferable a kidney or liver transplant patient. The dosage form releases the active substance over an extended period of time. It also provides improved pharmacokinetic parameters due to an extended and constant in vivo release including substantial decreased peak concentrations, despite increased bioavailability, substantial extended times for maximal concentration, and higher minimal concentrations when compared with conventional immediate release dosage forms and a recent modified release tacrolimus dosage form.

10. 发明申请

US20110256190A1 Modified release compositions comprising tacrolimus 有权
公开(公告)号：US20110256190A1
公开(公告)日：2011-10-20
申请号：US13167334
申请日：2011-06-23
申请人： Per HOLM , Tomas Norling
发明人： Per HOLM , Tomas Norling
IPC分类号： A61K31/436 , A61P37/06 , A61K9/14
CPC分类号： A61K31/436 , A61K9/0053 , A61K9/10 , A61K9/1611 , A61K9/1617 , A61K9/1623 , A61K9/1641 , A61K9/1652 , A61K9/2009 , A61K9/2013 , A61K9/2018 , A61K9/2027 , A61K9/2031 , A61K9/2054 , A61K9/2077 , A61K9/2095 , A61K9/2846 , A61K9/2893 , A61K31/00 , A61K31/439 , A61K31/4745 , Y10S514/885
摘要： A modified release composition comprising tacrolimus releases less than 20% w/w of the active ingredient within 0.5 hours when subjected to an in vitro dissolution test using USP Paddle method and using 0.1 N HCl as dissolution medium and has increased bioavailability by effectively reducing or even avoiding the effects of CYP3A4 metabolism. The modified composition may be coated with an enteric coating; and/or may comprise a solid dispersion or a solid solution of tacrolimus in a hydrophilic or water-miscible vehicle and one or more modifying release agents; and/or may comprise a solid dispersion or a solid solution of tacrolimus in an amphiphilic or hydrophobic vehicle and optionally one or more modifying release agents.

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