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
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- 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)
- Gastroenterology & Hepatology (AREA)
- Zoology (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)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Obesity (AREA)
- Emergency Medicine (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) | KR20110104081A (es) |
| CN (2) | CN102365025A (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) | SG173112A1 (es) |
| TN (1) | TN2011000354A1 (es) |
| WO (1) | WO2010088294A1 (es) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8940690B2 (en) | 2009-01-28 | 2015-01-27 | National Institutes Of Health (Nih) | Synthetic conjugates and uses thereof |
| WO2010088268A1 (en) | 2009-01-28 | 2010-08-05 | Smartcells, Inc. | Exogenously triggered controlled release materials and uses thereof |
| US9050370B2 (en) * | 2009-01-28 | 2015-06-09 | Smartcells, Inc. | Conjugate based systems for controlled drug delivery |
| WO2010107519A1 (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 |
| AU2011282977A1 (en) | 2010-07-28 | 2013-02-21 | Smartcells, Inc. | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
| AU2011282983A1 (en) * | 2010-07-28 | 2013-02-21 | Smartcells, Inc. | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
| CA2805902A1 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinant lectins, binding-site modified lectins and uses thereof |
| WO2012015692A2 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinantly expressed insulin polypeptides and uses thereof |
| WO2012050822A1 (en) * | 2010-10-14 | 2012-04-19 | Smartcells, Inc. | 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 |
| CA2937532A1 (en) * | 2013-01-22 | 2014-07-31 | Case Western Reserve University | N-terminal truncated insulin analogues |
| US9884125B2 (en) * | 2013-10-04 | 2018-02-06 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
| EP3280450A4 (en) * | 2015-04-08 | 2018-12-12 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
| BR112018074716A2 (pt) | 2016-06-02 | 2019-03-12 | Sanofi | conjugados de um agente farmacêutico e porção capaz de ligar-se a uma proteína sensível à glicose |
| WO2018136505A1 (en) | 2017-01-17 | 2018-07-26 | Wayne State University | Zwitterionic polymer-insulin compositions and related methods |
| EP3600381A4 (en) * | 2017-03-23 | 2021-06-16 | Merck Sharp & Dohme Corp. | GLUCOSE-ACTIVE INSULIN WITH A THREE-VALUE SUGAR CLUSTER FOR THE TREATMENT OF DIABETES |
| AU2017405304B2 (en) * | 2017-03-23 | 2022-03-03 | Victoria Link Limited | Heparan sulfate glycomimetic compounds and their pharmaceutical and cosmeceutical uses |
| KR20200095507A (ko) | 2017-12-01 | 2020-08-10 | 사노피 | 글루코오스 감지 단백질에 결합할 수 있는 모이어티 및 약제의 신규 접합체 |
| 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 |
| WO2020247297A1 (en) | 2019-06-06 | 2020-12-10 | Merck Sharp & Dohme Corp. | 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 |
| WO2022234030A1 (en) | 2021-05-05 | 2022-11-10 | Novo Nordisk A/S | Insulin on board for glucose sensitive insulin |
| EP4613738A1 (en) * | 2022-11-01 | 2025-09-10 | Samyang Holdings Corporation | Lipid having amide and ester functional groups, and method for producing same |
| CA3271735A1 (en) * | 2022-11-16 | 2025-05-20 | Samyang Holdings Corporation | Nanoparticle composition for drug delivery |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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