SK16552002A3 - Stála, biologicky zlúčiteľná, dobre znášateľná mikroemulzia voda v oleji a jej použitie - Google Patents
Stála, biologicky zlúčiteľná, dobre znášateľná mikroemulzia voda v oleji a jej použitie Download PDFInfo
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- SK16552002A3 SK16552002A3 SK1655-2002A SK16552002A SK16552002A3 SK 16552002 A3 SK16552002 A3 SK 16552002A3 SK 16552002 A SK16552002 A SK 16552002A SK 16552002 A3 SK16552002 A3 SK 16552002A3
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- Slovakia
- Prior art keywords
- microemulsion
- biologically active
- surfactant
- active compound
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
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IT2000MI001173A IT1318539B1 (it) | 2000-05-26 | 2000-05-26 | Composizioni farmaceutiche a rilascio prolungato per lasomministrazione parenterale di sostanze idrofile biologicamente |
PCT/EP2001/005949 WO2001089479A2 (en) | 2000-05-26 | 2001-05-23 | Sustained release pharmaceutical compositions for parenteral administration of hydrophilic compounds |
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US (1) | US7157099B2 (pt) |
EP (1) | EP1283700B1 (pt) |
JP (1) | JP4954423B2 (pt) |
KR (1) | KR100802625B1 (pt) |
CN (1) | CN100479856C (pt) |
AT (1) | ATE321533T1 (pt) |
AU (2) | AU8178601A (pt) |
BR (1) | BRPI0111016B8 (pt) |
CA (1) | CA2409854C (pt) |
CY (1) | CY1105262T1 (pt) |
CZ (1) | CZ302059B6 (pt) |
DE (1) | DE60118395T2 (pt) |
DK (1) | DK1283700T3 (pt) |
ES (1) | ES2257428T3 (pt) |
HR (1) | HRP20020929A2 (pt) |
HU (1) | HU228926B1 (pt) |
IL (1) | IL153011A0 (pt) |
IT (1) | IT1318539B1 (pt) |
MX (1) | MXPA02011539A (pt) |
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SI (1) | SI1283700T1 (pt) |
SK (1) | SK16552002A3 (pt) |
WO (1) | WO2001089479A2 (pt) |
YU (1) | YU88202A (pt) |
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Families Citing this family (115)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7658938B2 (en) | 1999-02-22 | 2010-02-09 | Merrion Reasearch III Limited | Solid oral dosage form containing an enhancer |
US8119159B2 (en) | 1999-02-22 | 2012-02-21 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
SI1787658T1 (sl) | 2005-11-10 | 2012-07-31 | Chemi Spa | Formulacije z trajnim sproščanjem somatostatin analognih inhibitorjev rastnega hormona |
MX2008012678A (es) | 2006-04-07 | 2008-12-17 | Merrion Res Iii Ltd | Forma de dosis oral solida que contiene un mejorador. |
KR100816065B1 (ko) * | 2006-11-27 | 2008-03-24 | 동국제약 주식회사 | 초기 방출억제 특성이 우수한 서방출성 마이크로캡슐의제조방법 및 이에 의해 제조되는 마이크로캡슐 |
RU2362544C2 (ru) * | 2007-04-09 | 2009-07-27 | Закрытое акционерное общество "Санкт-Петербургский институт фармации" | Наноэмульсия с биологически активными веществами |
CA2702135C (en) * | 2007-10-04 | 2013-08-20 | Daniel Py | Apparatus and method for formulating and aseptically filling liquid products |
WO2009137080A1 (en) * | 2008-05-07 | 2009-11-12 | Merrion Research Iii Limited | Compositions of gnrh related compounds and processes of preparation |
CN102711728B (zh) | 2010-01-13 | 2016-01-20 | 益普生制药股份有限公司 | 用于延缓释放生长抑素类似物的药物组合物的制备方法 |
WO2011120033A1 (en) | 2010-03-26 | 2011-09-29 | Merrion Research Iii Limited | Pharmaceutical compositions of selective factor xa inhibitors for oral administration |
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US9193973B2 (en) | 2010-12-10 | 2015-11-24 | Alynylam Pharmaceuticals, Inc. | Compositions and methods for increasing erythropoietin (EPO) production |
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CA2831284C (en) | 2011-03-29 | 2023-12-12 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of tmprss6 gene |
WO2012166903A1 (en) | 2011-06-02 | 2012-12-06 | President And Fellows Of Harvard College | Methods and uses for ex vivo tissue culture systems |
EP3564393A1 (en) | 2011-06-21 | 2019-11-06 | Alnylam Pharmaceuticals, Inc. | Assays and methods for determining activity of a therapeutic agent in a subject |
EP4092120A1 (en) | 2011-06-21 | 2022-11-23 | Alnylam Pharmaceuticals, Inc. | Angiopoietin-like 3 (anglptl3) irna compositions and methods of use thereof |
US20140235693A1 (en) | 2011-06-23 | 2014-08-21 | Alnylam Pharmaceuticals, Inc. | Serpina1 sirnas: compositions of matter and methods of treatment |
JP2014527036A (ja) | 2011-06-27 | 2014-10-09 | ザ ジャクソン ラボラトリー | 癌および自己免疫疾患の処置のための方法および組成物 |
US20140328811A1 (en) | 2011-08-01 | 2014-11-06 | Alnylam Pharmaceuticals, Inc. | Method for improving the success rate of hematopoietic stem cell transplants |
CN102552187B (zh) * | 2012-02-28 | 2015-10-28 | 大连医科大学 | 口服羟丝肽纳米粒及其制备方法 |
CN102552138A (zh) * | 2012-02-28 | 2012-07-11 | 大连医科大学 | 口服羟丝肽w/o微乳制剂及其制备方法 |
CA2866262C (en) * | 2012-03-05 | 2020-06-16 | Archer Daniels Midland Company | Microemulsions and uses thereof as delivery systems |
US9133461B2 (en) | 2012-04-10 | 2015-09-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the ALAS1 gene |
US9127274B2 (en) | 2012-04-26 | 2015-09-08 | Alnylam Pharmaceuticals, Inc. | Serpinc1 iRNA compositions and methods of use thereof |
PT2929031T (pt) | 2012-12-05 | 2018-01-19 | Alnylam Pharmaceuticals Inc | Composições de irna de pcsk9 e métodos de seu uso |
ES2649490T3 (es) | 2013-03-14 | 2018-01-12 | Alnylam Pharmaceuticals, Inc. | Composiciones de ARNi contra el componente C5 del complemento y métodos para su uso |
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EP2994167B1 (en) | 2013-05-06 | 2020-05-06 | Alnylam Pharmaceuticals, Inc. | Dosages and methods for delivering lipid formulated nucleic acid molecules |
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EP2832361A1 (en) * | 2013-07-29 | 2015-02-04 | Ipsen Pharma S.A.S. | Aqueous sustained release compositions of LHRH analogs |
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WO2015175510A1 (en) | 2014-05-12 | 2015-11-19 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating a serpinc1-associated disorder |
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WO2016040589A1 (en) | 2014-09-12 | 2016-03-17 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting complement component c5 and methods of use thereof |
JOP20200115A1 (ar) | 2014-10-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات)) |
EP3207138B1 (en) | 2014-10-17 | 2020-07-15 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof |
WO2016069694A2 (en) | 2014-10-30 | 2016-05-06 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof |
JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
WO2016081444A1 (en) | 2014-11-17 | 2016-05-26 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof |
TW201702218A (zh) | 2014-12-12 | 2017-01-16 | 美國杰克森實驗室 | 關於治療癌症、自體免疫疾病及神經退化性疾病之組合物及方法 |
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EP3250191B1 (en) | 2015-01-29 | 2024-01-17 | Novo Nordisk A/S | Tablets comprising glp-1 agonist and enteric coating |
AU2016219263B2 (en) | 2015-02-13 | 2022-12-01 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (PNPLA3) iRNA compositions and methods of use thereof |
WO2016164746A1 (en) | 2015-04-08 | 2016-10-13 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the lect2 gene |
EP3283631A1 (en) | 2015-04-13 | 2018-02-21 | Alnylam Pharmaceuticals, Inc. | Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof |
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EP3307316A1 (en) | 2015-06-12 | 2018-04-18 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions and methods of use thereof |
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WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
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JP7028764B2 (ja) | 2015-09-02 | 2022-03-02 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | プログラム細胞死1リガンド1(PD-L1)iRNA組成物およびその使用方法 |
TW201718857A (zh) | 2015-09-14 | 2017-06-01 | 艾爾妮蘭製藥公司 | 用於抑制alas1基因表現之組合物及方法 |
EP3350328A1 (en) | 2015-09-14 | 2018-07-25 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting patatin-like phospholipase domain containing 3 (pnpla3) and methods of use thereof |
EP3362458A1 (en) | 2015-10-16 | 2018-08-22 | Invictus Oncology Pvt. Ltd. | Fluorescent anticancer platinum drugs |
IL308717A (en) | 2015-12-07 | 2024-01-01 | Genzyme Corp | Methods and preparations for the treatment of diseases related to SERPINC1 |
WO2017100542A1 (en) | 2015-12-10 | 2017-06-15 | Alnylam Pharmaceuticals, Inc. | Sterol regulatory element binding protein (srebp) chaperone (scap) irna compositions and methods of use thereof |
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JPH08505367A (ja) * | 1992-10-16 | 1996-06-11 | スミスクライン・ビーチャム・コーポレイション | 医薬用エマルジョン組成物 |
SE512663C2 (sv) * | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
WO1999021533A2 (en) | 1997-10-24 | 1999-05-06 | Neorx Corporation | Delivery vehicles for bioactive agents and uses thereof |
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