ECSP11011240A - Conjugados de insulina cristalina - Google Patents
Conjugados de insulina cristalinaInfo
- Publication number
- ECSP11011240A ECSP11011240A EC2011011240A ECSP11011240A ECSP11011240A EC SP11011240 A ECSP11011240 A EC SP11011240A EC 2011011240 A EC2011011240 A EC 2011011240A EC SP11011240 A ECSP11011240 A EC SP11011240A EC SP11011240 A ECSP11011240 A EC SP11011240A
- Authority
- EC
- Ecuador
- Prior art keywords
- insulin
- crystalline
- formulations
- conjugates
- protamine
- Prior art date
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title abstract 30
- 102000004877 Insulin Human genes 0.000 title abstract 17
- 108090001061 Insulin Proteins 0.000 title abstract 17
- 229940125396 insulin Drugs 0.000 title abstract 15
- 239000013078 crystal Substances 0.000 title 1
- 238000009472 formulation Methods 0.000 abstract 8
- 239000000203 mixture Substances 0.000 abstract 8
- 150000001720 carbohydrates Chemical class 0.000 abstract 5
- 102000007327 Protamines Human genes 0.000 abstract 4
- 108010007568 Protamines Proteins 0.000 abstract 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract 4
- 229940048914 protamine Drugs 0.000 abstract 4
- 238000013268 sustained release Methods 0.000 abstract 4
- 239000012730 sustained-release form Substances 0.000 abstract 4
- 239000011701 zinc Substances 0.000 abstract 4
- 229910052725 zinc Inorganic materials 0.000 abstract 4
- 238000000034 method Methods 0.000 abstract 3
- 230000003285 pharmacodynamic effect Effects 0.000 abstract 3
- 239000004026 insulin derivative Substances 0.000 abstract 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 abstract 1
- 238000005054 agglomeration Methods 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 238000002425 crystallisation Methods 0.000 abstract 1
- 230000008025 crystallization Effects 0.000 abstract 1
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 239000008103 glucose Substances 0.000 abstract 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 239000002245 particle Substances 0.000 abstract 1
- 238000003860 storage Methods 0.000 abstract 1
- 230000001839 systemic circulation Effects 0.000 abstract 1
- 230000009885 systemic effect Effects 0.000 abstract 1
Classifications
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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
- A61K38/28—Insulins
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
- C07K17/02—Peptides being immobilised on, or in, an organic carrier
- C07K17/10—Peptides being immobilised on, or in, an organic carrier the carrier being a carbohydrate
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Obesity (AREA)
- Toxicology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
En un aspecto, la divulgación proporciona métodos para controlar los perfiles farmacocinéticos (PK) y/o farmacodinámicos (PD) de insulina de una forma que es sensible a las concentraciones sistémicas de un sacárido tal como la glucosa. Como se discute en los Ejemplos, se descubrió que cuando la insulina fuera conjugada con ligandos sacáridos de alta afinidad, pudo hacerse para exhibir perfiles PK/PD que respondieran a cambios de concentración sacárida aún en ausencia de una molécula multivalente y exógena fijadora de sacáridos tal como Con A. Este hallazgo fue inesperado y proporciona una oportunidad sin precedentes para generar sistemas simples de insulina sensibles a sacáridos libres de lectina.Las formulaciones de liberación sostenida de insulinas convencionales comúnmente se utilizan para retardar la liberación de insulina en circulación sistémica. Por ejemplo, las formulaciones PZI (insulina de protamina de zinc) pueden utilizarse para este propósito. Cuando se formulan insulinas convencionales con protamina y zinc, generalmente se producen formulaciones de liberación sostenida cristalinas. Por el contrario, cuando se formulan los conjugados de insulina descritos en la presente con protamina y zinc utilizando métodos similares, se producen formulaciones amorfas, y se requiere mucha más protamina y zinc para proporcionar liberación sostenida que la requerida para insulinas convencionales, ej. RHI (insulina humana recombinante). Sorprendentemente se ha descubierto que ciertos conjugados de insulina descritos en la presente pueden cristalizarse. Los conjugados de insulina son difíciles de cristalizar utilizando condiciones estándares de cristalización de insulina, más probablemente debido a sus estructuras estéricamente voluminosas que contienen sacáridos. Como se describió en la presente, los conjugados de insulina cristalina de la presente divulgación pueden entonces formularse para proporcionar formulaciones de liberación sostenida cristalinas. La presente divulgación proporciona conjugados de insulina cristalina y formulaciones de los mismos. También se proporcionan métodos para fabricar y utilizar conjugados de insulina cristalina. Las formulaciones cristalinas de los conjugados de insulina pueden ser ventajosas para mejorar reproducibilidad de lote en lote, aumentando estabilidad de la formulación, y disminuyendo la aglomeración de partículas durante largos periodos de almacenamiento.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14787809P | 2009-01-28 | 2009-01-28 | |
| US15964309P | 2009-03-12 | 2009-03-12 | |
| US16210709P | 2009-03-20 | 2009-03-20 | |
| US16308409P | 2009-03-25 | 2009-03-25 | |
| US21989709P | 2009-06-24 | 2009-06-24 | |
| US22357209P | 2009-07-07 | 2009-07-07 | |
| US25285709P | 2009-10-19 | 2009-10-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ECSP11011240A true ECSP11011240A (es) | 2011-11-30 |
Family
ID=42395986
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EC2011011240A ECSP11011240A (es) | 2009-01-28 | 2011-07-28 | Conjugados de insulina cristalina |
Country Status (24)
| Country | Link |
|---|---|
| US (5) | US9050370B2 (es) |
| EP (1) | EP2391218B1 (es) |
| JP (3) | JP5508438B2 (es) |
| KR (2) | KR101635689B1 (es) |
| CN (2) | CN105753965A (es) |
| AU (2) | AU2015202871B2 (es) |
| BR (1) | BRPI1007457A2 (es) |
| CA (2) | CA2932926C (es) |
| CO (1) | CO6400173A2 (es) |
| CR (1) | CR20110408A (es) |
| DO (1) | DOP2011000244A (es) |
| EA (1) | EA027757B1 (es) |
| EC (1) | ECSP11011240A (es) |
| ES (1) | ES2791683T3 (es) |
| GT (1) | GT201100208A (es) |
| IL (1) | IL214099A0 (es) |
| MA (1) | MA33064B1 (es) |
| MX (1) | MX2011007929A (es) |
| NI (1) | NI201100150A (es) |
| NZ (1) | NZ594248A (es) |
| PE (1) | PE20120583A1 (es) |
| SG (3) | SG193837A1 (es) |
| TN (1) | TN2011000354A1 (es) |
| WO (1) | WO2010088294A1 (es) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2011007929A (es) * | 2009-01-28 | 2011-08-17 | Smartcells Inc | Sistemas basados en conjugados para entrega farmacologica controlada. |
| CA2750223A1 (en) | 2009-01-28 | 2010-08-05 | Smartcells, Inc. | Exogenously triggered controlled release materials and uses thereof |
| EP2391217A4 (en) | 2009-01-28 | 2015-05-20 | Smartcells Inc | SYNTHETIC CONJUGATES AND ITS USE |
| US9095623B2 (en) | 2009-03-20 | 2015-08-04 | Smartcells, Inc. | Terminally-functionalized conjugates and uses thereof |
| CA2754950A1 (en) | 2009-03-20 | 2010-09-23 | Smartcells, Inc. | Terminally-functionalized conjugates and uses thereof |
| EP2598171A2 (en) * | 2010-07-28 | 2013-06-05 | Smartcells, Inc. | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
| WO2012015681A2 (en) * | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
| CA2806399A1 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinantly expressed insulin polypeptides and uses thereof |
| JP2013541500A (ja) | 2010-07-28 | 2013-11-14 | スマートセルズ・インコーポレイテツド | 組換えレクチン、結合部位修飾レクチンおよびそれらの用途 |
| US20130302825A1 (en) * | 2010-10-14 | 2013-11-14 | Merck | Uses of macrophage mannose receptor to screen compounds and uses of these compounds |
| AR087433A1 (es) * | 2011-08-08 | 2014-03-26 | Merck Sharp & Dohme | Analogos de insulina n-glicosilados |
| TWI439288B (zh) * | 2012-10-05 | 2014-06-01 | Univ China Medical | 藥用載體及其製備方法與用途 |
| JP6445453B2 (ja) * | 2012-11-28 | 2018-12-26 | ビクトリア リンク リミテッド | 樹状コア化合物 |
| JP6735561B2 (ja) | 2012-12-03 | 2020-08-05 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｏ−グリコシル化カルボキシ末端部分（ｃｔｐ）ペプチド系のインスリンおよびインスリン類似体 |
| EP2948166B1 (en) * | 2013-01-22 | 2020-12-09 | Case Western Reserve University | N-terminal truncated insulin analogues |
| WO2015051052A2 (en) * | 2013-10-04 | 2015-04-09 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
| EP3280450A4 (en) * | 2015-04-08 | 2018-12-12 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
| CN109562185A (zh) * | 2016-06-02 | 2019-04-02 | 赛诺菲 | 药剂与能够结合葡萄糖感应蛋白的部分的新颖缀合物 |
| WO2018136505A1 (en) | 2017-01-17 | 2018-07-26 | Wayne State University | Zwitterionic polymer-insulin compositions and related methods |
| WO2018174725A1 (en) | 2017-03-23 | 2018-09-27 | Victoria Link Limited | Heparan sulfate glycomimetic compounds and their pharmaceutical and cosmeceutical uses |
| US11041009B2 (en) | 2017-03-23 | 2021-06-22 | Merck Sharp & Dohme Corp. | Glucose responsive insulin comprising a tri-valent sugar cluster for treatment of diabetes |
| JP2021504402A (ja) | 2017-12-01 | 2021-02-15 | サノフイＳａｎｏｆｉ | 薬剤とグルコース感知タンパク質に結合し得る部分との新規のコンジュゲート |
| WO2019125878A1 (en) * | 2017-12-18 | 2019-06-27 | Merck Sharp & Dohme Corp. | Conjugate based systems for controlled insulin delivery |
| CN108610494B (zh) * | 2018-03-20 | 2020-11-06 | 南京理工大学 | 聚醚砜/功能性含糖聚合物杂化膜的制备方法 |
| CN110146605A (zh) * | 2019-04-19 | 2019-08-20 | 南通联亚药业有限公司 | 一种测定格列吡嗪原料药及其缓释片中特定基因毒性杂质的分析方法 |
| US12427187B2 (en) | 2019-06-06 | 2025-09-30 | Merck Sharp & Dohme Llc | Glucose-responsive insulin conjugates |
| CN113773400B (zh) * | 2020-06-09 | 2023-08-18 | 宁波鲲鹏生物科技有限公司 | 一种门冬胰岛素衍生物及其应用 |
| CN113773398B (zh) * | 2020-06-10 | 2023-05-23 | 宁波鲲鹏生物科技有限公司 | 一种德谷胰岛素衍生物及其应用 |
| CN112480184A (zh) * | 2020-12-09 | 2021-03-12 | 上海应用技术大学 | 一种利用梯度点击化学合成含多种糖的树枝化糖胺的方法 |
| US20240242810A1 (en) | 2021-05-05 | 2024-07-18 | Novo Nordisk A/S | Insulin on board for glucose sensitive insulin |
| CN120019041A (zh) * | 2022-11-01 | 2025-05-16 | 三养控股公司 | 具有酰胺官能团和酯官能团的脂质及其制备方法 |
| AU2023382803A1 (en) * | 2022-11-16 | 2025-05-22 | Samyang Holdings Corporation | Nanoparticle composition for drug delivery |
Family Cites Families (131)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US39055A (en) | 1863-06-30 | Improvement in churns | ||
| US3591574A (en) | 1968-05-29 | 1971-07-06 | American Home Prod | Tri-n-phenylglycyl derivatives of insulin |
| DE1793517C3 (de) | 1968-09-28 | 1974-12-05 | Farbwerke Hoechst Ag, Vormals Meister Lucius & Bruening, 6000 Frankfurt | N(Al),N(B29>Bis-(tert.-butyloxycarbonyl)-insulin und Verfahren zu seiner Herstellung |
| US3697502A (en) * | 1969-11-03 | 1972-10-10 | Christensen Henry M | Method of making iron dextran-preparations |
| US3847890A (en) | 1971-11-01 | 1974-11-12 | A Green | Acidic monosaccharide-substituted proteins |
| US4086257A (en) | 1976-10-12 | 1978-04-25 | Sears Barry D | Phosphatidyl quaternary ammonium compounds |
| US4377567A (en) | 1978-10-02 | 1983-03-22 | The Procter & Gamble Company | Lipid membrane drug delivery |
| EP0009842B1 (en) | 1978-10-02 | 1982-11-10 | THE PROCTER & GAMBLE COMPANY | Liposomes for drug delivery and composition containing a liposome drug system |
| US4348387A (en) | 1979-07-31 | 1982-09-07 | The Rockefeller University | Method and system for the controlled release of biologically active substances to a body fluid |
| US4421685A (en) | 1980-03-27 | 1983-12-20 | Eli Lilly And Company | Process for producing an insulin |
| JPS608000B2 (ja) | 1980-04-11 | 1985-02-28 | 呉羽化学工業株式会社 | アミノフエニル誘導体及び該誘導体を含有する生理活性剤 |
| US4435173A (en) | 1982-03-05 | 1984-03-06 | Delta Medical Industries | Variable rate syringe pump for insulin delivery |
| US4498843A (en) | 1982-08-02 | 1985-02-12 | Schneider Philip H | Insulin infusion pump |
| US4444683A (en) | 1982-11-17 | 1984-04-24 | University Of Utah | Glycosylated insulin derivatives |
| US4603044A (en) | 1983-01-06 | 1986-07-29 | Technology Unlimited, Inc. | Hepatocyte Directed Vesicle delivery system |
| EP0119650A3 (en) | 1983-03-21 | 1987-09-30 | THE PROCTER & GAMBLE COMPANY | Galactosyl-insulin conjugates useful in treating diabetics |
| US4863896A (en) | 1984-05-03 | 1989-09-05 | Technology Unlimited, Inc. | Diabetic control by combined insulin forms |
| DK160633C (da) | 1985-05-15 | 1991-09-02 | Henning Munk Ejlersen | Slangepumpe, isaer til avendelse som insulinpumpe |
| US5239062A (en) * | 1986-03-20 | 1993-08-24 | Dana-Farber Cancer Institute, Inc. | Blocked lectins, methods and affinity support for making same using affinity ligands, and method of killing selected cell populations having reduced nonselective cytotoxicity |
| US5395924A (en) | 1986-03-20 | 1995-03-07 | Dana-Farber Cancer Institute, Inc. | Blocked lectins; methods and affinity support for making the same using affinity ligands; and method of killing selected cell populations having reduced non-selective cytotoxicity |
| US5527524A (en) * | 1986-08-18 | 1996-06-18 | The Dow Chemical Company | Dense star polymer conjugates |
| US4853218A (en) * | 1987-02-24 | 1989-08-01 | Schering Corporation | Zinc-protamine-alpha interferon complex |
| US5062841A (en) | 1988-08-12 | 1991-11-05 | The Regents Of The University Of California | Implantable, self-regulating mechanochemical insulin pump |
| DK111489D0 (da) | 1989-03-08 | 1989-03-08 | Novo Nordisk As | Peptider |
| CA2027930C (en) | 1989-10-19 | 1998-06-30 | Tsuyoshi Miyazaki | Polymer complexes of a sugar response type |
| IL99699A (en) * | 1990-10-10 | 2002-04-21 | Autoimmune Inc | Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes |
| RU2003351C1 (ru) * | 1991-06-26 | 1993-11-30 | Липов Борис Петрович; Сафронов Игорь Николаевич | Инъектор |
| GB9200638D0 (en) | 1992-01-10 | 1992-03-11 | Leicester Polytechnic | Drug system |
| ATE192487T1 (de) | 1992-02-13 | 2000-05-15 | Surmodics Inc | Immobilisierung eines chemischen spezies in einer vernetzten matrix |
| GB9316895D0 (en) | 1993-08-13 | 1993-09-29 | Guy S And St Thomas Hospitals | Hepatoselective insulin analogues |
| GB9313484D0 (en) | 1993-06-30 | 1993-08-11 | Univ Montfort | Drug system ii |
| US6342225B1 (en) | 1993-08-13 | 2002-01-29 | Deutshces Wollforschungsinstitut | Pharmaceutical active conjugates |
| US6869930B1 (en) | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| KR100310122B1 (ko) * | 1993-09-17 | 2002-04-24 | 한센 핀 베네드, 안네 제헤르, 웨이콥 마리안느 | 아실화된인슐린 |
| US6011007A (en) | 1993-09-17 | 2000-01-04 | Novo Nordisk A/S | Acylated insulin |
| US5474978A (en) | 1994-06-16 | 1995-12-12 | Eli Lilly And Company | Insulin analog formulations |
| US5504188A (en) | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals |
| US5461031A (en) | 1994-06-16 | 1995-10-24 | Eli Lilly And Company | Monomeric insulin analog formulations |
| US6500645B1 (en) | 1994-06-17 | 2002-12-31 | Novo Nordisk A/S | N-terminally extended proteins expressed in yeast |
| US5547929A (en) | 1994-09-12 | 1996-08-20 | Eli Lilly And Company | Insulin analog formulations |
| US5693609A (en) | 1994-11-17 | 1997-12-02 | Eli Lilly And Company | Acylated insulin analogs |
| AR002976A1 (es) | 1995-03-31 | 1998-05-27 | Lilly Co Eli | Formulaciones farmaceuticas parenterales de efecto prolongado de insulina; cristales de dichos analogos aplicables en dichas formulaciones yprocedimiento de las formulaciones mencionadas |
| US5902603A (en) | 1995-09-14 | 1999-05-11 | Cygnus, Inc. | Polyurethane hydrogel drug reservoirs for use in transdermal drug delivery systems, and associated methods of manufacture and use |
| TW520293B (en) | 1995-11-22 | 2003-02-11 | Univ Johns Hopkins Med | Delivery system to enhance cellular uptake of biomolecules |
| US5723589A (en) | 1995-12-21 | 1998-03-03 | Icn Pharmaceuticals | Carbohydrate conjugated bio-active compounds |
| US5866538A (en) | 1996-06-20 | 1999-02-02 | Novo Nordisk A/S | Insulin preparations containing NaCl |
| US5948751A (en) | 1996-06-20 | 1999-09-07 | Novo Nordisk A/S | X14-mannitol |
| US5905140A (en) | 1996-07-11 | 1999-05-18 | Novo Nordisk A/S, Novo Alle | Selective acylation method |
| EP0954589A1 (en) | 1997-01-24 | 1999-11-10 | Novo Nordisk A/S | Synthetic leader peptide sequences |
| CO4750643A1 (es) | 1997-06-13 | 1999-03-31 | Lilly Co Eli | Formulacion estable de la insulina que contiene l-arginina y protamina |
| US6444641B1 (en) | 1997-10-24 | 2002-09-03 | Eli Lilly Company | Fatty acid-acylated insulin analogs |
| PE123799A1 (es) | 1997-10-24 | 1999-12-13 | Lilly Co Eli | Composiciones insolubles de insulina |
| ZA989744B (en) | 1997-10-31 | 2000-04-26 | Lilly Co Eli | Method for administering acylated insulin. |
| EP1044016B1 (en) | 1998-01-09 | 2005-03-16 | Novo Nordisk A/S | Stabilised insulin compositions |
| DE69926226T2 (de) | 1998-04-15 | 2006-05-24 | Novo Nordisk A/S | Neues verfahren zur trennung von proteinen unter verwendung eines ca++ enthaltenden elutionsmittels |
| US6300319B1 (en) * | 1998-06-16 | 2001-10-09 | Isis Pharmaceuticals, Inc. | Targeted oligonucleotide conjugates |
| US6844166B1 (en) | 1998-09-11 | 2005-01-18 | Sensor Technologies Inc. | Recombinant reduced valency carbohydrate binding ligands |
| US6323311B1 (en) | 1999-09-22 | 2001-11-27 | University Of Utah Research Foundation | Synthesis of insulin derivatives |
| US6521738B2 (en) | 1999-12-29 | 2003-02-18 | Novo Nordisk A/S | Method for making insulin precursors and insulin precursor analogs |
| US6777207B2 (en) | 1999-12-29 | 2004-08-17 | Novo Nordisk A/S | Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast |
| EP1290024A1 (en) | 2000-06-02 | 2003-03-12 | Novo Nordisk A/S | Glucose dependent release of insulin from glucose sensing insulin derivatives |
| US7316999B2 (en) | 2000-06-02 | 2008-01-08 | Novo Nordisk A/S | Glucose dependent release of insulin from glucose sensing insulin derivatives |
| US6650951B1 (en) | 2000-06-19 | 2003-11-18 | International Business Machines Corporation | Method and insulin pump for providing a forgotten bolus warning |
| EP1301585A2 (en) | 2000-07-13 | 2003-04-16 | The Ohio State University Research Foundation | Multimeric biopolymers as structural elements, sensors and actuators in microsystems |
| US7060675B2 (en) | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| AU2002258490A1 (en) | 2001-03-12 | 2003-06-17 | Clemson University | Polysaccharide-based polmerizable hydrogels |
| US7105314B2 (en) | 2001-04-02 | 2006-09-12 | Novo Nordisk A/S | Method for making human insulin precursors |
| DK2279755T3 (da) * | 2001-10-10 | 2014-05-26 | Ratiopharm Gmbh | Remodellering og glycokonjugering af fibroblastvækstfaktor (FGF) |
| CA2478543A1 (en) | 2001-10-26 | 2003-04-26 | The Uab Research Foundation | Multidrug multiligand conjugates for targeted drug delivery |
| US6736796B2 (en) | 2001-11-26 | 2004-05-18 | Nili-Med Ltd. | Fluid drug delivery device |
| US7473680B2 (en) * | 2001-11-28 | 2009-01-06 | Neose Technologies, Inc. | Remodeling and glycoconjugation of peptides |
| US7317000B2 (en) | 2001-12-02 | 2008-01-08 | Novo Nordisk A/S | Glucose-dependent insulins |
| EP1453860A2 (en) * | 2001-12-02 | 2004-09-08 | Novo Nordisk A/S | Novel glucose-dependant insulins |
| US7349688B2 (en) | 2001-12-07 | 2008-03-25 | Ntt Docomo, Inc. | Mobile communications terminal, application program execution state control method, and execution state control computer program product |
| US6852104B2 (en) | 2002-02-28 | 2005-02-08 | Smiths Medical Md, Inc. | Programmable insulin pump |
| US6744350B2 (en) | 2002-02-28 | 2004-06-01 | Smiths Medical Md, Inc. | Insulin pump having missed meal bolus alarm |
| DE10209821A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung von Proteinen an ein modifiziertes Polysaccharid |
| DE60335797D1 (de) | 2002-05-07 | 2011-03-03 | Novo Nordisk As | Lösliche formulierungen, die monomeres insulin und acyliertes insulin enthalten |
| AU2003254066B2 (en) | 2002-07-19 | 2009-08-27 | The Regents Of The University Of California | Dendrimers as molecular translocators |
| US7993108B2 (en) | 2002-10-09 | 2011-08-09 | Abbott Diabetes Care Inc. | Variable volume, shape memory actuated insulin dispensing pump |
| AU2002368314A1 (en) * | 2002-10-29 | 2004-05-25 | Ranbaxy Laboratories Limited | Iminosugar derivatives as glucosidase inhibitors |
| CA2509382A1 (en) * | 2002-12-17 | 2004-07-08 | Todd C. Zion | Stimuli-responsive systems for controlled drug delivery |
| AU2003294912B2 (en) | 2002-12-20 | 2009-06-04 | Greenovation Biotech Gmbh | Production of heterologous glycosylated proteins in bryophyte cells |
| JPWO2004101619A1 (ja) * | 2003-05-15 | 2006-10-26 | 塩野義製薬株式会社 | 機能的糖ペプチドの合理的設計および合成 |
| JP2007532096A (ja) | 2003-11-14 | 2007-11-15 | ノボ ノルディスク アクティーゼルスカブ | アシル化されたインスリンの製造方法 |
| US20080102114A1 (en) | 2004-04-23 | 2008-05-01 | Panduranga Rao Koritala | Microparticles and Nanoparticles for the Transmucosal Delivery of Therapeutic and Diagnostic Agents |
| WO2006008238A1 (en) | 2004-07-16 | 2006-01-26 | Novo Nordisk A/S | Method for selective acylation |
| CN101027318B (zh) | 2004-07-19 | 2016-05-25 | 比奥孔有限公司 | 胰岛素-低聚物共轭物，制剂及其用途 |
| WO2006062685A2 (en) * | 2004-11-11 | 2006-06-15 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
| TWI376234B (en) | 2005-02-01 | 2012-11-11 | Msd Oss Bv | Conjugates of a polypeptide and an oligosaccharide |
| US20060247154A1 (en) | 2005-02-24 | 2006-11-02 | Lifescan, Inc. | Concanavalin a, methods of expressing, purifying and characterizing concanavalina, and sensors including the same |
| US20070207498A1 (en) | 2005-02-24 | 2007-09-06 | Lifescan, Inc. | Design and construction of dimeric concanavalin a mutants |
| WO2006102762A1 (en) | 2005-04-01 | 2006-10-05 | Mcmaster University | Glucose responsive microgels |
| ES2535854T3 (es) | 2005-09-30 | 2015-05-18 | Miikana Therapeutics, Inc. | Compuestos de pirazol sustituidos |
| WO2007042470A2 (en) | 2005-10-10 | 2007-04-19 | N.V. Organon | Antithrombotic compound |
| US7517856B2 (en) | 2005-10-11 | 2009-04-14 | Ben-Gurion University Of The Negev Research And Development Authority | Bioconjugates comprising sulfated polysaccharides and their uses |
| US7687608B2 (en) | 2005-10-19 | 2010-03-30 | Smartcells, Inc. | Methods for reducing the mitogenicity of lectin compositions |
| US8722620B2 (en) | 2006-02-27 | 2014-05-13 | Novo Nordisk A/S | Insulin derivatives |
| EP2043689A4 (en) | 2006-07-24 | 2013-08-07 | Univ Duke | ACTIVE ADMINISTRATION WITH STIMULUS-REPONSIVE BIOPOLYMERS |
| US8299026B2 (en) | 2006-07-25 | 2012-10-30 | Lipoxen Technologies Limited | Derivatisation of erythropoietin (EPO) |
| FR2904315B1 (fr) | 2006-07-26 | 2012-12-14 | Centre Nat Rech Scient | Composes pyridaziniques et pyrroliques, procedes d'obtention et applications |
| US20080172028A1 (en) | 2006-10-17 | 2008-07-17 | Blomquist Michael L | Insulin pump having selectable insulin absorption models |
| US7515060B2 (en) | 2006-10-17 | 2009-04-07 | Smiths Medical Md, Inc. | Insulin pump for the visually impaired |
| CN101273961A (zh) | 2007-03-30 | 2008-10-01 | 中国人民解放军总医院 | 葡萄糖敏感水凝胶 |
| US20090053167A1 (en) | 2007-05-14 | 2009-02-26 | Neose Technologies, Inc. | C-, S- and N-glycosylation of peptides |
| US20090005726A1 (en) | 2007-06-27 | 2009-01-01 | Steven Paul Jones | Insulin Pump Having Expected Bolus Interval and an Early Bolus Interval |
| WO2009033588A2 (en) | 2007-09-11 | 2009-03-19 | F. Hoffmann-La-Roche Ag | Self-controlled insulin delivery system |
| WO2009059450A1 (en) | 2007-11-05 | 2009-05-14 | Shanghai Jiaotong University | Peptide ligand directed drug delivery |
| GB2446247B (en) | 2007-11-27 | 2008-12-17 | Robert Joseph Wagener | Homeostatic insulin pump |
| US20090177154A1 (en) | 2008-01-08 | 2009-07-09 | Michael Blomquist | Insulin pump with convenience features |
| WO2009089396A2 (en) | 2008-01-08 | 2009-07-16 | Neose Technologies, Inc. | Glycoconjugation of polypeptides using oligosaccharyltransferases |
| US20090177142A1 (en) | 2008-01-09 | 2009-07-09 | Smiths Medical Md, Inc | Insulin pump with add-on modules |
| RU2381238C2 (ru) | 2008-01-31 | 2010-02-10 | Ордена Трудового Красного Знамени Институт нефтехимического синтеза им. А.В. Топчиева Российской академии наук (статус государственного учреждения) | Способ получения глюкозочувствительных полимерных гидрогелей |
| RU2495131C2 (ru) | 2008-02-19 | 2013-10-10 | Байокон Лимитид | Способ получения рекомбинантного инсулина гларгина |
| DK2141620T3 (en) | 2008-07-01 | 2019-02-18 | Hoffmann La Roche | Insulin pump and method for controlling one of the insulin pump's user interface |
| CA2750223A1 (en) * | 2009-01-28 | 2010-08-05 | Smartcells, Inc. | Exogenously triggered controlled release materials and uses thereof |
| BRPI1007466A2 (pt) * | 2009-01-28 | 2018-06-12 | Smartcells Inc | conjugado de insulina cristalina, formulação de liberação prolongada, e, sistema de distribuição de bomba |
| EP2391217A4 (en) * | 2009-01-28 | 2015-05-20 | Smartcells Inc | SYNTHETIC CONJUGATES AND ITS USE |
| WO2010088261A1 (en) * | 2009-01-28 | 2010-08-05 | Smartcells, Inc. | Binding-site modified lectins and uses thereof |
| EP2391380A4 (en) * | 2009-01-28 | 2015-05-13 | Smartcells Inc | NETWORKED MATERIALS ON POLYNUCLEOTIDE ADAPTASE BASE AND APPLICATIONS THEREOF |
| MX2011007929A (es) * | 2009-01-28 | 2011-08-17 | Smartcells Inc | Sistemas basados en conjugados para entrega farmacologica controlada. |
| CA2754950A1 (en) * | 2009-03-20 | 2010-09-23 | Smartcells, Inc. | Terminally-functionalized conjugates and uses thereof |
| US9095623B2 (en) * | 2009-03-20 | 2015-08-04 | Smartcells, Inc. | Terminally-functionalized conjugates and uses thereof |
| WO2010107520A1 (en) * | 2009-03-20 | 2010-09-23 | Smartcells, Inc. | Soluble non-depot insulin conjugates and uses thereof |
| WO2011000823A1 (en) | 2009-06-30 | 2011-01-06 | Novo Nordisk A/S | Insulin derivatives |
| EP2598171A2 (en) * | 2010-07-28 | 2013-06-05 | Smartcells, Inc. | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
| CA2806399A1 (en) * | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinantly expressed insulin polypeptides and uses thereof |
| JP2013541500A (ja) * | 2010-07-28 | 2013-11-14 | スマートセルズ・インコーポレイテツド | 組換えレクチン、結合部位修飾レクチンおよびそれらの用途 |
| WO2015051052A2 (en) * | 2013-10-04 | 2015-04-09 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
| EP3280450A4 (en) * | 2015-04-08 | 2018-12-12 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
| US9899205B2 (en) * | 2016-05-25 | 2018-02-20 | Kla-Tencor Corporation | System and method for inhibiting VUV radiative emission of a laser-sustained plasma source |
-
2010
- 2010-01-27 MX MX2011007929A patent/MX2011007929A/es active IP Right Grant
- 2010-01-27 CN CN201610103747.9A patent/CN105753965A/zh active Pending
- 2010-01-27 KR KR1020147001684A patent/KR101635689B1/ko not_active Expired - Fee Related
- 2010-01-27 PE PE2011001411A patent/PE20120583A1/es not_active Application Discontinuation
- 2010-01-27 CN CN201080015055XA patent/CN102365025A/zh active Pending
- 2010-01-27 SG SG2013065412A patent/SG193837A1/en unknown
- 2010-01-27 EP EP10736354.1A patent/EP2391218B1/en active Active
- 2010-01-27 MA MA34121A patent/MA33064B1/fr unknown
- 2010-01-27 US US13/145,532 patent/US9050370B2/en active Active
- 2010-01-27 WO PCT/US2010/022268 patent/WO2010088294A1/en not_active Ceased
- 2010-01-27 BR BRPI1007457-0A patent/BRPI1007457A2/pt not_active IP Right Cessation
- 2010-01-27 CA CA2932926A patent/CA2932926C/en not_active Expired - Fee Related
- 2010-01-27 EA EA201170986A patent/EA027757B1/ru not_active IP Right Cessation
- 2010-01-27 SG SG2014006597A patent/SG2014006597A/en unknown
- 2010-01-27 NZ NZ594248A patent/NZ594248A/en not_active IP Right Cessation
- 2010-01-27 KR KR1020117017641A patent/KR20110104081A/ko not_active Ceased
- 2010-01-27 CA CA2750262A patent/CA2750262C/en not_active Expired - Fee Related
- 2010-01-27 ES ES10736354T patent/ES2791683T3/es active Active
- 2010-01-27 SG SG2011053311A patent/SG173112A1/en unknown
- 2010-01-27 JP JP2011548259A patent/JP5508438B2/ja not_active Expired - Fee Related
-
2011
- 2011-07-14 IL IL214099A patent/IL214099A0/en unknown
- 2011-07-15 TN TN2011000354A patent/TN2011000354A1/fr unknown
- 2011-07-27 GT GT201100208A patent/GT201100208A/es unknown
- 2011-07-27 NI NI201100150A patent/NI201100150A/es unknown
- 2011-07-28 EC EC2011011240A patent/ECSP11011240A/es unknown
- 2011-07-28 CO CO11095147A patent/CO6400173A2/es not_active Application Discontinuation
- 2011-07-28 CR CR20110408A patent/CR20110408A/es unknown
- 2011-07-28 DO DO2011000244A patent/DOP2011000244A/es unknown
-
2014
- 2014-03-20 JP JP2014057357A patent/JP5834103B2/ja not_active Expired - Fee Related
- 2014-05-30 US US14/291,021 patent/US9265838B2/en active Active
-
2015
- 2015-05-27 AU AU2015202871A patent/AU2015202871B2/en not_active Ceased
- 2015-05-27 AU AU2015202872A patent/AU2015202872B2/en not_active Ceased
- 2015-06-04 US US14/731,016 patent/US9579391B2/en active Active
- 2015-11-02 JP JP2015215913A patent/JP6040301B2/ja not_active Expired - Fee Related
-
2016
- 2016-02-10 US US15/040,004 patent/US20160193351A1/en not_active Abandoned
-
2017
- 2017-08-18 US US15/680,262 patent/US10398781B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ECSP11011240A (es) | Conjugados de insulina cristalina | |
| Chen et al. | Revisiting carbazole: origin, impurity, and properties | |
| Pandozzi et al. | A spectroscopic analysis of blue and ultraviolet upconverted emissions from Gd3Ga5O12: Tm3+, Yb3+ nanocrystals | |
| Sun et al. | Plasmon-enhanced energy transfer for improved upconversion of infrared radiation in doped-lanthanide nanocrystals | |
| Jeitschko | The crystal structure of Fe2AlB2 | |
| MX346145B (es) | Composición de sistema de suministro de arnsi in vivo basado en péptidos. | |
| ECSP077250A (es) | Solución para infusión de dihidropteridinonas estabilizada para el almacenamiento | |
| Aroua et al. | C60 pyrrolidine bis-carboxylic acid derivative as a versatile precursor for biocompatible fullerenes | |
| BR112012018116A2 (pt) | "hormônios do crescimento com eficácia in vivo prolongada" | |
| ATE482700T1 (de) | Stabilisierte pharmazeutische zusammensetzung | |
| Li et al. | Effects of polymorphic DNA on the fluorescent properties of silver nanoclusters | |
| Jia et al. | Upconversion luminescence from Ln3+ (Ho3+, Pr3+) ion-doped BaCl2 particles via NIR light of sun excitation | |
| He et al. | Perovskite spin light-emitting diodes with simultaneously high electroluminescence dissymmetry and high external quantum efficiency | |
| Zhang et al. | Unraveling the Excited-State Dynamics of Er3+ in LiErF4-Based Upconversion Nanoparticles | |
| Wu et al. | Controlling Morphological Dimensions of Organic Charge‐Transfer Cocrystal by Manipulating the Growth Kinetics for Optical Waveguide Applications | |
| Wang et al. | Transient absorption probe of intermolecular triplet excimer of naphthalene in fluid solutions: Identification of the species based on comparison to the intramolecular triplet excimers of covalently-linked dimers | |
| BR112014013906A2 (pt) | ésteres de fosfato aromáticos como componentes de formulação agroquímica | |
| MD4484B1 (ro) | Forma cristalină VIII a agomelatinei, procedeu de preparare, utilizarea acesteia şi compoziţie farmaceutică care o conţine | |
| PE20131327A1 (es) | Forma cristalina delta de la sal de arginina de perindoprilo, su procedimiento de preparacion, y las composiciones farmaceuticas que la contienen | |
| JP5858274B2 (ja) | 結晶化促進方法、結晶化解析方法、結晶の製造方法、結晶化装置の制御プログラム、記録媒体、及び結晶化装置 | |
| Li et al. | Sucralose, an activator of the glucose-sensing receptor, increases ATP by calcium-dependent and-independent mechanisms | |
| PE20100153A1 (es) | Nuevo procedimiento de obtencion de la forma cristalina v de la agomelatina | |
| CN104194770A (zh) | 一种具有紫色发光性能的荧光材料及其制备方法 | |
| Li et al. | Sb2O3-induced tapered ZnO nanowire arrays: the kinetics of radial growth and morphology control | |
| Choi et al. | In Situ Synthesis of Core–Shell Structured Perovskite Nanofibers for Stretchable Color-Conversion Film |