TW202304501A - Glp-1組成物及其用途 - Google Patents
Glp-1組成物及其用途 Download PDFInfo
- Publication number
- TW202304501A TW202304501A TW111139129A TW111139129A TW202304501A TW 202304501 A TW202304501 A TW 202304501A TW 111139129 A TW111139129 A TW 111139129A TW 111139129 A TW111139129 A TW 111139129A TW 202304501 A TW202304501 A TW 202304501A
- Authority
- TW
- Taiwan
- Prior art keywords
- composition
- semaglutide
- phenol
- compositions
- phosphate
- Prior art date
Links
Classifications
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K38/26—Glucagons
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61P3/04—Anorexiants; Antiobesity 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
- 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
Abstract
本發明係關於包含不超過0.01% (w/w)苯酚之GLP-1肽索馬魯肽的醫藥組成物、其製備物、包含此類組成物之套組、以及其用途。
Description
本發明係關於包含GLP-1肽索馬魯肽(semaglutide)之醫藥組成物的領域。
已知GLP-1肽在液體溶液中易於出現穩定性缺乏,例如物理穩定性缺乏。因此,需要穩定性甚至更佳的包含GLP-1肽之液體醫藥組成物。此類改進之穩定性可為物理穩定性及/或化學穩定性。
在一些具體實例中,本發明係關於包含索馬魯肽及不超過0.01% (w/w)苯酚之液體醫藥組成物。在一些具體實例中,本發明係關於包含如本文中所定義之醫藥組成物的套組。在一些具體實例中,本發明係關於如本文中所定義之用於醫藥的醫藥組成物。
在一些具體實例中,本發明係關於包含GLP-1肽索馬魯肽及不超過0.01% (w/w)苯酚之液體醫藥組成物。意外地,本發明者發現此類組成物具有改進之化學及/或物理穩定性。在一些具體實例中,組成物不包含苯酚。在一些具體實例中,組成物包含0.01至10 mg/ml索馬魯肽。在一些具體實例中,組成物之pH值介於6.0至10.0範圍內,例如pH 7.0至7.8。
在一些具體實例中,本發明之組成物為包含索馬魯肽及不超過0.01% (w/w)苯酚之液體醫藥組成物,其中該組成物
a.用於非經腸投予;
b.為包含至少60% w/w水之水溶液;或
c.進一步包含選自由緩衝劑或等張劑組成之群的一或多種醫藥學上可接受之賦形劑。
在一些具體實例中,本發明之組成物為液體醫藥組成物,其包含索馬魯肽、不超過0.01% (w/w)苯酚及視情況之一或多種醫藥學上可接受之賦形劑,其中調配物用於非經腸投予,例如皮下投予。
在一些具體實例中,本發明之組成物為液體醫藥組成物,其包含索馬魯肽、不超過0.01% (w/w)苯酚、至少60% w/w水以及視情況之一或多種醫藥學上可接受之賦形劑。
在一些具體實例中,如本文中所使用之術語「
穩定性」係指索馬魯肽在液體醫藥組成物中之穩定性。在一些具體實例中,穩定性為GLP-1肽之化學穩定性(例如,藉由HPLC所確定,例如本文中之分析(I)),及視情況之GLP-1肽之物理穩定性(例如,藉由硫代黃素T (Thioflavine T)分析所確定,例如本文中之分析(II))。
在一些具體實例中,如本文中所使用之與索馬魯肽有關的術語「
化學穩定性」係指索馬魯肽化合物之共價鍵實質上完整。在一些具體實例中,GLP-1肽之化學穩定性藉由HPLC確定,例如本文中之分析(I)。在一些具體實例中,若在在25℃下儲存3個月後,在至少80% (w/v)之該GLP-1肽中其共價鍵為完整的,則組成物具有化學穩定性。在一些具體實例中,索馬魯肽之化學穩定性藉由本文中之分析(IV)確定。
在一些具體實例中,如本文中所使用之與索馬魯肽有關的術語「
物理穩定性」係指實質上不形成聚集體之索馬魯肽,例如呈原纖維形式。在一些具體實例中,物理穩定性藉由硫代黃素T分析確定,例如本文中之分析(II)。
在一些具體實例中,本發明之組成物為穩定醫藥組成物。當在本文中使用時,術語「穩定醫藥組成物」係指包含GLP-1肽之醫藥組成物,例如溶液或懸浮液,且其組成物在儲存後包含至少80% (w/v)之該GLP-1肽(例如,在25℃下靜態儲存3個月後)。穩定性測試之儲存條件可為2至8℃,例如5℃,或至少在5℃下2.5年。或者,穩定性測試之儲存條件可為至少4週,例如6週或3個月,視情況在30℃下。此穩定醫藥組成物之儲存條件可為在5℃下1或2年。此穩定醫藥組成物之儲存條件可為在5℃下3年。或者,此儲存之條件可為在25℃下24小時或1週。在又一替代例中,此儲存之條件可為室溫下兩個月,例如多達兩個月。
在一些具體實例中,GLP-1肽之化學穩定性需要至少80% (w/v) (例如至少90% (w/v)或至少95% (w/v))之該GLP-1肽在儲存時段結束時保持其共價鍵完整。在一些具體實例中,GLP-1肽之化學穩定性需要至少95% (w/v) (例如至少97% (w/v)或至少99% (w/v))之該GLP-1肽在儲存時段結束時保持其共價鍵完整。
本發明之組成物包含不超過0.01% (w/w)苯酚。在一些具體實例中,組成物實質上不包含苯酚。
醫藥組成物
術語「醫藥組成物」及「組成物」在本文中可互換使用,且係指適用於向有需要之個體投予的醫藥組成物。
在一些具體實例中,組成物包含0.01至100 mg/ml索馬魯肽。在一些具體實例中,組成物包含0.1至50 mg/ml索馬魯肽,例如0.5至25 mg/ml或1至15 mg/ml。在一些具體實例中,組成物包含0.1至10 mg/ml索馬魯肽,例如0.5至5 mg/ml或1至2 mg/ml。在一些具體實例中,組成物包含0.01至10 mg/ml索馬魯肽,例如0.01至5 mg/ml。在一些具體實例中,組成物包含不超過9 mg/ml索馬魯肽,例如不超過8 mg/ml或不超過7 mg/ml。在一些具體實例中,組成物包含不超過6 mg/ml索馬魯肽,例如不超過5 mg/ml或不超過4 mg/ml。在一些具體實例中,組成物包含不超過3 mg/ml索馬魯肽,例如不超過2 mg/ml或不超過1 mg/ml。在一些具體實例中,組成物包含至少0.01 mg/ml索馬魯肽,例如至少0.02 mg/ml或至少0.05 mg/ml。在一些具體實例中,組成物包含1.34 mg/ml索馬魯肽。
在一些具體實例中,本發明之組成物之pH值介於3至10範圍內,例如pH 6至10或6至9。在一些具體實例中,本發明之組成物之pH值介於pH 6.5至8.5範圍內,例如pH 7.0至7.8。
在一些具體實例中,本發明之組成物包含一或多種醫藥學上可接受之賦形劑。
在一些具體實例中,本發明之組成物包含等張劑,例如丙二醇。在一些具體實例中,等張劑為丙二醇或氯化鈉。
在一些具體實例中,本發明之組成物包含緩衝劑,例如磷酸鹽緩衝劑、TRIS、檸檬酸鹽或緩衝劑緩衝劑。在一些具體實例中,磷酸鹽緩衝劑為磷酸鈉緩衝劑,例如磷酸氫二鈉。
在一些具體實例中,本發明之組成物不包含防腐劑。
本發明之組成物呈液體醫藥組成物形式。在一些具體實例中,液體醫藥組成物為溶液或懸浮液。在一些具體實例中,本發明之組成物呈溶液形式,例如水溶液。在一些具體實例中,如本文中所使用之術語「水溶液」係指包含至少60% w/w水的溶液。在一些具體實例中,水溶液包含60-99% w/w水。在一些具體實例中,水溶液包含至少75% w/w水,例如至少80% w/w水或至少85% w/w水。在一些具體實例中,水溶液包含至少90% w/w水,例如至少92% w/w水或至少94% w/w水。
索馬魯肽
GLP-1肽索馬魯肽可如WO2006/097537,實施例4中所描述來製備。索馬魯肽亦稱為N
6.26-{18-[N-(17-羧基十七醯基)-L-γ-麩胺醯基]-10-側氧基-3,6,12,15-四氧雜-9,18-二氮雜十八醯基}-[8-(2-胺基-2-丙酸),34-L-精胺酸]人類升糖素類肽1(7-37),見WHO藥物信息第24卷第1,2010期。在一些具體實例中,索馬魯肽可以其完全或部分電離化形式存在於組成物中;例如一或多種羧酸基(-COOH)可去質子化為羧酸酯基團(-COO-),及/或一或多種胺基(-NH
2)可質子化為-NH
3+基團。在一些具體實例中,將索馬魯肽添加至呈鹽形式之組成物。
投予及套組
本發明之組成物用於非經腸投予。在一些具體實例中,組成物用於皮下投予。
在一些具體實例中,本發明之組成物每週投予一次。在一些具體實例中,本發明之組成物每日投予一次、每兩天投予一次或每三天投予一次。
在一些具體實例中,本發明係關於一種包含如本文中所定義之醫藥組成物及使用說明書的套組。在一些具體實例中,使用說明書包含藥物包裝插頁。
在一些具體實例中,本發明係關於一種包含如本文中所定義之醫藥組成物及注射裝置的套組。在一些具體實例中,注射裝置選自由耐用筆及預填充筆組成之群。耐用筆之實例為NovoPen® 4或NovoPen® 5 (兩者均來自丹麥的諾佛.儂迪克股份有限公司)。預填充筆之實例為FlexPen® (諾佛.儂迪克股份有限公司,丹麥)。
適應症
在一些具體實例中,本發明之組成物用於醫藥。在一些具體實例中,本發明之組成物可用於以下醫藥治療:
(i)預防及/或治療所有形式之糖尿病,諸如高血糖症、2型糖尿病、葡萄糖耐受性異常、1型糖尿病、非胰島素依賴性糖尿病、年輕起病成人型糖尿病(maturity onset diabetes of the young;MODY)、妊娠期糖尿病及/或HbA1C減少;
(ii)延緩或預防糖尿病進程,例如2型糖尿病之進程,延緩葡萄糖耐受性異常(impaired glucose tolerance;IGT)發展至需要胰島素之2型糖尿病,及/或延緩非胰島素需要2型糖尿病發展至需要胰島素之2型糖尿病;
(iii)例如藉由減少食物攝入、減輕體重、抑制食慾、誘發飽腹感來預防及/或治療飲食障礙,例如肥胖症;治療或預防暴食症、神經性貪食症及/或由投予抗精神病藥或類固醇引發之肥胖症;減少胃運動;及/或延緩胃排空。
在一些具體實例中,適應症為(i)。在一些具體實例中,適應症為(ii)。在又一特定態樣中,適應症為(iii)。在一些具體實例中,適應症為2型糖尿病及/或肥胖症。
在一些具體實例中,方法或用途包含預防、治療、減輕及/或誘發本文中所定義之一或多種疾病或病況。在一些具體實例中,適應症為(i)及(iii)。在一些具體實例中,適應症為(ii)及(iii)。在一些具體實例中,本發明包含投予有效量之GLP-1肽。在一些具體實例中,本發明係關於投予有效量之GLP-1肽。
一般而言,患有肥胖症之所有個體亦視為患有超重。在一些具體實例中,本發明係關於一種治療或預防肥胖症之方法。在一些具體實例中,本發明係關於一種用於治療或預防肥胖症之組成物的用途。在一些具體實例中,患有肥胖症之個體為人類,諸如成人或孩童(包括嬰兒、兒童及青少年)。身體質量指數(Body mass index;BMI)為基於高度及體重之體脂肪之量度。計算式為BMI = 以公斤為單位之重量/以米為單位之高度
2。患有肥胖症之人類個體之BMI可為>30;此個體亦可稱為肥胖性的。在一些具體實例中,患有肥胖症之人類個體之BMI可為>35或介於>30至<40範圍內。在一些具體實例中,肥胖症為重度肥胖症或病態肥胖症,其中人類個體之BMI可為>40。
在一些具體實例中,本發明係關於一種(視情況在至少一種重量相關之共生病症存在下)治療或預防超重之方法。在一些具體實例中,本發明係關於一種用於(視情況在至少一種重量相關之共生病症存在下)治療或預防超重之組成物的用途。在一些具體實例中,患有超重之個體為人類,諸如成人或孩童(包括嬰兒、兒童及青少年)。在一些具體實例中,患有超重之人類個體之BMI可為>25,例如>27。在一些具體實例中,患有超重之人類個體之BMI介於25至<30範圍內或介於27至<30範圍內。在一些具體實例中,重量相關之共生病症選自由以下組成之群:高血壓、糖尿病(諸如2型糖尿病)、血脂異常、高膽固醇及阻塞性睡眠呼吸暫停。
在一些具體實例中,本發明係關於一種減輕體重之方法。在一些具體實例中,本發明係關於一種用於減少體重之組成物的用途。根據本發明之經受體重減少之人類的BMI可為>25,例如>27或>30。在一些具體實例中,根據本發明之經受體重減少之人類的BMI可為>35或>40。術語「體重減少」可包括治療或預防肥胖症及/或超重。
在一些具體實例中,如本文中所使用,相對於數目或時間間隔給定之具體值可理解為具體值或理解為約具體值(例如,加或減具體值之百分之10)。
本發明之具體實例
以下為本發明之非限制性具體實例:
1.一種包含索馬魯肽及不超過0.01% (w/w)苯酚之液體醫藥組成物。
2.一種包含索馬魯肽及實質上無苯酚之液體醫藥組成物。
3.如技術方案1或2之組成物,其中該組成物不包含苯酚。
4.如前述技術方案中任一項之組成物,其中該組成物為包含至少60% w/w水之水溶液,例如至少70% w/w水或至少80% w/w水。
5.如前述技術方案中任一項之組成物,其中索馬魯肽之濃度為0.5至10 mg/ml之該組成物。
6.如前述技術方案中任一項之組成物,其中該索馬魯肽呈醫藥學上可接受之鹽的形式。
7.如前述技術方案中任一項之組成物,其中該組成物包含一或多種醫藥學上可接受之賦形劑。
8.如前述技術方案中任一項之組成物,其中該組成物包含用於調整pH值的一或多種試劑,例如HCl、NaOH或乙酸。
9.如前述技術方案中任一項之組成物,其中該組成物包含緩衝劑及/或等張劑。
10.如前述技術方案中任一項之組成物,其中該緩衝劑存在於濃度為0.01至50 mM之該組成物中。
11.如前述技術方案中任一項之組成物,其中該緩衝劑為磷酸鹽緩衝劑。
12.如前述技術方案中任一項之組成物,其中該磷酸鹽緩衝劑選自由以下組成之群:磷酸二氫鈉、磷酸氫二鈉及磷酸鈉。
13.如前述技術方案中任一項之組成物,其中該等張劑以8 mg/ml至50 mg/ml (例如14 mg/ml至30 mg/ml)之該組成物的濃度存在。
14.如前述技術方案中任一項之組成物,其中該等張劑為丙二醇。
15.如前述技術方案中任一項之組成物,其中該組成物不包含防腐劑。
16.如前述技術方案中任一項之組成物,其中該組成物之pH值介於6.0至10.0範圍內。
17.如前述技術方案中任一項之組成物,其中該組成物用於非經腸投予。
18.如前述技術方案中任一項之組成物,其中該組成物用於皮下投予。
19.一種套組,其包含如前述技術方案中任一項之醫藥組成物及使用說明書。
20.一種包含如前述技術方案中任一項之醫藥組成物及注射裝置之套組,該注射裝置用於向個體投予該組成物,其中該注射裝置選自由耐用筆及預填充筆組成之群。
21.如前述技術方案中任一項之醫藥組成物,其用於醫藥。
22.如前述技術方案中任一項之醫藥組成物,其用於治療糖尿病或肥胖症。
23.一種用於預防或治療糖尿病或肥胖症的方法,其中向有需要之個體投予如前述技術方案中任一項之醫藥組成物。
實施例一般方法及特徵界定
製備索馬魯肽組成物:
除非另外指出,否則索馬魯肽組成物藉由將緩衝劑(例如,磷酸氫二鈉二水合物)、等張劑(例如,丙二醇)及視情況之防腐劑(苯酚)溶解於水中來製備。將索馬魯肽溶解於其中,使用氫氧化鈉及/或鹽酸將pH值調整至7.4,且最後藉由由0.22 μm無菌過濾器過濾對組成物進行滅菌。
製備利拉魯肽 ( liraglutide ) 組成物:
除非另外指出,否則利拉魯肽組成物由溶液1及溶液2製備:溶液1藉由將緩衝劑(磷酸氫二鈉二水合物)、等張劑(甘露醇)及視情況之防腐劑(苯酚)溶解於水中來製備。溶液2藉由在緩慢攪拌時溶解利拉魯肽來製備。將溶液1及溶液2混合,使用氫氧化鈉及/或鹽酸將pH值調整至8.15,且最後藉由由0.22 μm無菌過濾器過濾來對組成物進行滅菌。
分析 (I) : 確定索馬魯肽組成物之高分子量蛋白質 (High Molecular Weight Proteins ; HMWP) 含量
使用尺寸排外層析法(size exclusion chromatography;SE-HPLC)來進行對HMWP含量之確定,該尺寸排外層析法使用沃特斯(Waters)胰島素HMWP柱,利用移動相之氯化鈉、磷酸鈉、磷酸及異丙醇等度溶離,且在280 nm下檢測。HMWP之含量以%形式給出為相對於HMWP及索馬魯肽單體峰之總面積的早於索馬魯肽單體峰溶離之層析峰(亦即HMWP峰)的組合面積。
分析 (II) :經由 ThT 評估索馬魯肽組成物之物理穩定性
此分析之目的為評估GLP-1肽在水溶液中之物理穩定性。
肽或蛋白質之低物理穩定性可引起澱粉狀蛋白原纖維形式。原纖維為藉由可溶性蛋白質之聚集形成且由β片層結構主導之結構上非常有序的絲狀巨分子結構。成熟原纖維為不溶性且抗降解。出於藥品質量及患者安全起見,期望最小化及控制在治療性肽及蛋白質之醫藥組成物中的原纖維化事件。可藉由目視檢查樣本來評估蛋白質聚集,包括原纖維化。可藉由使用硫代黃素T (ThT) (對原纖維具有高特異性之小分子指示劑探針)來評估纖維化。當與原纖維結合時,相比於呈溶液狀態之ThT,ThT具有不同螢光標記[Naiki等人(1989) Anal. Biochem. 177, 244-249;LeVine (1999) Methods. Enzymol. 309, 274-284]。
提出部分摺疊之肽中間物之形成作為原纖維化之一般引發機制。少量此等中間物成核以形成其上可組合有其他中間物且進行原纖維化之模板。滯後時間對應於時間間隔,其中產生細胞核之臨界量且表觀速率常數(apparent rate constant)為形成原纖維自身之速率。因此,描述於盤讀取器上進行之ThT分析中的滯後時間視為呈溶液狀態之肽組成物之原纖維化傾向之指示。
在進行分析前,將ThT添加至來自H
2O中之儲備溶液之樣本直至樣本呈20 μM之最終濃度。將包含GLP-1肽之組成物的200 μl等分樣本放入各孔中放入有玻璃細珠(2.8至3.2 mm,Whitehouse Scientific)之96孔微量滴定盤(光學0.4 mL黑色Thermo Scientific Nunc)中。通常,將各樣本之八個複本放在該盤上。該盤用密封帶(Thermo Scientific Nunc)密封。
對ThT螢光發光之在給定溫度下之培養、震盪及量測在BMG FLUOStar Omega或BMG FLUOStar Optima中進行。在40℃下利用2 mm振幅以300 rpm之的雙軌道搖動來培養該盤。使用穿過450 nm濾光器之激發及穿過480 nm濾光器之發射量測來進行螢光量測。每20分鐘對盤進行量測,持續所需時間段。各量測之間,如所描述震盪且加熱該盤。
確定臨限值為在1 h 13 min時間加100 RFU下於該盤上量測之最高ThT螢光(在相對螢光單元(relative fluorescence units;RFU)中)。臨限值隨後用於使用BMG FLUOstar軟體中之「臨限時間(time to threshold)」方法來計算滯後時間。
分析 (III) :確定利拉魯肽純度
使用高效液相層析法(high performance liquid chromatography;HPLC)來進行純度確定,該高效液相層析法使用沃特斯XTerra™ MS C18柱,利用兩個移動相之梯度溶離,其中一個移動相為水性磷酸銨緩衝劑(pH 8)/乙腈混合物且另一移動相為乙腈/水。檢測在215 nm下進行。
分析 (IV) :確定索馬魯肽中之雜質總和
使用反相高效液相層析法(reversed phase high performance liquid chromatography;RP-HPLC)來進行索馬魯肽純度之確定,該反相高效液相層析法使用Kinetex C18柱,利用後接兩個移動相之梯度溶離之等度溶離,其中一個移動相為水性磷酸鹽緩衝劑/乙腈混合物且另一移動相為水性乙腈/異丙醇混合物。檢測在210 nm下進行。索馬魯肽之純度作為雜質總和以%形式給出為相對於索馬魯肽單體峰之所有層析峰之組合面積。
實施例 1 :索馬魯肽
在此實驗中測試包含索馬魯肽之組成物。所測試組成物在pH 7.4下於水溶液中含有索馬魯肽(如表1中所說明)、丙二醇(14 mg/ml)、磷酸氫二鈉二水合物(1.42 mg/ml)及視情況之苯酚(5.5 mg/ml) (如表1中所說明)。如本文中在製備之一般方法部分中所描述來製備此等組成物。藉由本文中在實驗開始時所描述之分析(I)且在25℃、30℃或37℃下儲存後來確定由HMWP表示之化學穩定性。藉由本文中所描述之分析(II)來確定由硫代黃素T (ThT)分析表示之物理穩定性。
結果給出於表2及3中。意外地,此等結果顯示相對於含有苯酚之組成物,在不含苯酚之組成物中,索馬魯肽之物理及化學穩定性得到改進。表3中顯示之結果為8個測試樣本之平均值。
表 1 .實施例1中測試之組成物
表 2.在不同溫度下儲存後,索馬魯肽組成物之化學穩定性,由高分子量蛋白質(HMWP)之含量表示。較低HMWP濃度對應於較佳化學穩定性。
表 3.索馬魯肽組成物之物理穩定性,由硫代黃素T (ThT)分析表示。較長滯後時間對應於較佳物理穩定性。
實施例2 (參考):利拉魯肽
組成物編號 | 描述 |
1 | 索馬魯肽1 mg/ml,含有苯酚 |
2 | 索馬魯肽1 mg/ml,不含苯酚 |
3 | 索馬魯肽1.34 mg/ml,含有苯酚 |
4 | 索馬魯肽1.34 mg/ml,不含苯酚 |
5 | 索馬魯肽0.5 mg/ml,不含苯酚 |
6 | 索馬魯肽0.5 mg/ml,含有苯酚 |
7 | 索馬魯肽1.0 mg/ml,不含苯酚 |
8 | 索馬魯肽1.0 mg/ml,含有苯酚 |
9 | 索馬魯肽2.0 mg/ml,不含苯酚 |
10 | 索馬魯肽2.0 mg/ml,含有苯酚 |
組成物編號 | HMWP (%) | |||
0個月 | 25 ℃6個月 | 30 ℃3個月 | 37 ℃3個月 | |
1 | 0.1 | 2.0 | 1.9 | 4.1 |
2 (無苯酚) | 0.1 | 0.3 | 0.3 | 0.5 |
3 | 0.1 | 1.9 | 1.8 | 3.9 |
4 (無苯酚) | 0.1 | 0.3 | 0.4 | 0.6 |
組成物 編號 | 滯後時間(小時) | |
5 (無苯酚) | > 117 | |
6 | 19 | |
7 (無苯酚) | > 117 | |
8 | 35 | |
9 (無苯酚) | > 117 | |
10 | 35 |
鑒於GLP-1化合物利拉魯肽(與索馬魯肽相反)在不含苯酚之組成物中較不化學穩定,實例1之結果亦出人意料。此等結果顯示於表5中。
如下獲得表5中之結果:測試包含利拉魯肽之組成物。所測試組成物在pH 7.4下於水溶液中含有利拉魯肽(如表4中所說明)、甘露醇(36.9 mg/ml)、磷酸氫二鈉(1.42 mg/ml)及視情況之苯酚(如表4中所說明)。如本文中在製備之一般方法部分中所描述來製備此等組成物。藉由本文中在實驗開始時所描述之分析(III)且在25℃下或在37℃下儲存後來確定由純度表示之化學穩定性。
表 4 .實施例中2測試之組成物
表 5 .在不同溫度下儲存後,包含利拉魯肽之組成物之化學穩定性,由純度表示。較高純度對應於較佳化學穩定性。
實施例3:索馬魯肽-額外實驗
組成物編號 | 描述 |
11 | 利拉魯肽(3 mg/ml),不含苯酚(pH 7.4) |
12 | 利拉魯肽(3 mg/ml),苯酚(0.04 mg/ml) (pH 7.4) |
13 | 利拉魯肽(3 mg/ml),苯酚(0.16 mg/ml) (pH 7.4) |
14 | 利拉魯肽(3 mg/ml),苯酚(0.8 mg/ml) (pH 7.4) |
15 | 利拉魯肽(3 mg/ml),苯酚(2.5 mg/ml) (pH 7.4) |
組成物編號 | 純度(%) | ||||||
0個月 | 25 ℃下3個月 | 37 ℃ 下3個月 | |||||
11 (無苯酚) | 98 | 88 | 72 | ||||
12 | 98 | 93 | 80 | ||||
13 | 98 | 94 | 81 | ||||
14 | 97 | 95 | 83 | ||||
15 | 98 | 95 | 84 | ||||
在此實驗中測試包含索馬魯肽之組成物。所測試組成物在pH 7.0、7.4或7.8下於水溶液中含有索馬魯肽、等張劑(丙二醇(14 mg/ml)或氯化鈉(6.3 mg/ml))、視情況之緩衝劑(磷酸氫二鈉二水合物(1.42 mg/ml)或檸檬酸三鈉二水合物(2.35 mg/ml))及視情況之苯酚(5.5 mg/ml或0.1 mg/ml);所測試各組成物之細節顯示於表6中。如本文中在製備之一般方法部分中所描述來製備該等組成物。由HMWP表示之化學穩定性藉由分析(I)確定,且由雜質總和表示之化學穩定性藉由本文中在實驗開始時所描述之分析(IV)且在30℃下儲存後來確定。由硫代黃素T (ThT)分析表示之物理穩定性藉由本文中所描述之分析(II)確定。
結果給出於表7及8中。與實例1之結果一致,此等結果顯示相對於含有5.5 mg/ml下之苯酚的組成物,在不具有或具有低苯酚濃度之組成物中,索馬魯肽之物理穩定性及化學穩定性得到改進。結果顯示相對於含有苯酚之組成物,在不含苯酚之包含緩衝劑檸檬酸三鈉二水合物或無緩衝劑或等張劑氯化鈉之組成物中,索馬魯肽之物理穩定性及化學穩定性亦得到改進。相對於含有5.5 mg/ml苯酚之組成物,對於類似於不含苯酚之組成物的含有0.1 mg/ml苯酚之組成物,化學及物理穩定性得到改進。此針對pH 7.0至7.8且索馬魯肽濃度0.110 mg/ml之組成物而展示。
表 6.實施例中3測試之組成物
*)磷酸鹽:磷酸氫二鈉二水合物,1.42 mg/ml。**) PG:丙二醇,14 mg/ml。***)檸檬酸鹽:檸檬酸三鈉二水合物,2.35 mg/ml。
#)無:未添加呈緩衝劑形式之醫藥學上之賦形劑
##) NaCl:氯化鈉,6.3 mg/ml。
表 7 .在30℃溫度下儲存後,索馬魯肽組成物之化學穩定性,由高分子量蛋白質(HMWP)之含量及雜質之總和表示。較低HMWP濃度及雜質總和濃度對應於較佳化學穩定性。
DS:索馬魯肽。
1物理上不穩定> 30℃下1個月。
表 8.索馬魯肽組成物之物理穩定性,由硫代黃素T (ThT)分析表示。較長滯後時間對應於較佳物理穩定性。
結果為8個測試樣本之平均值。DS:索馬魯肽。
組成物編號 | 組成物成分 | ||||||
索馬魯肽 (mg/ml) | 苯酚 (mg/ml) | 緩衝劑 | 等張劑 | pH | |||
1 | 0.5 | 0 | 磷酸鹽* | PG** | 7.0 | ||
2 | 0.5 | 0.1 | 磷酸鹽 | PG | 7.0 | ||
3 | 0.5 | 5.5 | 磷酸鹽 | PG | 7.0 | ||
4 | 0.5 | 0 | 磷酸鹽 | PG | 7.4 | ||
5 | 0.5 | 0.1 | 磷酸鹽 | PG | 7.4 | ||
6 | 0.5 | 5.5 | 磷酸鹽 | PG | 7.4 | ||
7 | 0.5 | 0 | 磷酸鹽 | PG | 7.8 | ||
8 | 0.5 | 0.1 | 磷酸鹽 | PG | 7.8 | ||
9 | 0.5 | 5.5 | 磷酸鹽 | PG | 7.8 | ||
10 | 10 | 0 | 磷酸鹽 | PG | 7.0 | ||
11 | 10 | 0.1 | 磷酸鹽 | PG | 7.0 | ||
12 | 10 | 5.5 | 磷酸鹽 | PG | 7.0 | ||
13 | 10 | 0 | 磷酸鹽 | PG | 7.4 | ||
14 | 10 | 0.1 | 磷酸鹽 | PG | 7.4 | ||
15 | 10 | 5.5 | 磷酸鹽 | PG | 7.4 | ||
16 | 10 | 0 | 磷酸鹽 | PG | 7.8 | ||
17 | 10 | 0.1 | 磷酸鹽 | PG | 7.8 | ||
18 | 10 | 5.5 | 磷酸鹽 | PG | 7.8 | ||
19 | 0.1 | 0 | 磷酸鹽 | PG | 7.4 | ||
20 | 0.1 | 5.5 | 磷酸鹽 | PG | 7.4 | ||
21 | 0.5 | 0 | 磷酸鹽 | 檸檬酸鹽*** | 7.4 | ||
22 | 0.5 | 5.5 | 磷酸鹽 | 檸檬酸鹽 | 7.4 | ||
23 | 0.5 | 0 | 磷酸鹽 | 無# | 7.4 | ||
24 | 0.5 | 5.5 | 磷酸鹽 | 無 | 7.4 | ||
25 | 0.5 | 0 | NaCl## | PG | 7.4 | ||
26 | 0.5 | 5.5 | NaCl | PG | 7.4 | ||
組成物 編號 | DS (mg/ml) | 苯酚 (mg/ml) | 化學穩定性 | ||||
HMWP (%) | 雜誌總和(%) | ||||||
0個月 | 30 ℃ | 0個月 | 30 ℃ | ||||
3個月 | 3個月 | ||||||
1 (pH 7.0) | 0.5 | 0 | 0.1 | 0.3 | 3.1 | 7.0 | |
2 (pH 7.0) | 0.5 | 0.1 | 0.1 | 0.3 | 3.2 | 7.2 | |
3 (pH 7.0) | 0.5 | 5.5 | 0.1 | 1.4 | 3.2 | 7.8 | |
4 (pH 7.4) | 0.5 | 0 | 0.1 | 0.3 | 3.1 | 6.7 | |
5 (pH 7.4) | 0.5 | 0.1 | 0.1 | 0.3 | 3.2 | 6.6 | |
6 (pH 7.4) | 0.5 | 5.5 | 0.1 | 2.4 | 3.2 | 8.4 | |
7 (pH 7.8) | 0.5 | 0 | 0.1 | 0.2 | 3.1 | 6.5 | |
8 (pH 7.8) | 0.5 | 0.1 | 0.1 | 0.3 | 3.2 | 6.6 | |
9 (pH 7.8) | 0.5 | 5.5 | 0.1 | 4.8 | 3.1 | 10.6 | |
10 (pH 7.0) | 10 | 0 | 0.1 | 1.4 | 3.1 | 8.4 | |
11 (pH 7.0) | 10 | 0.1 | 0.1 | 0.7 | 3.1 | 7.7 | |
12 (pH 7.0) | 10 | 5.5 | 0.1 | N/A 1 | 3.0 | N/A 1 | |
13 (pH 7.4) | 10 | 0 | 0.1 | 0.9 | 3.1 | 7.8 | |
14 (pH 7.4) | 10 | 0.1 | 0.1 | 0.7 | 3.1 | 6.9 | |
15 (pH 7.4) | 10 | 5.5 | 0.1 | 0.8 | 3.0 | 6.9 | |
16 (pH 7.8) | 10 | 0 | 0.1 | 0.9 | 3.0 | 6.6 | |
17 (pH 7.8) | 10 | 0.1 | 0.1 | 0.6 | 3.1 | 6.8 | |
18 (pH 7.8) | 10 | 5.5 | 0.1 | 1.0 | 3.1 | 6.9 | |
19 (低DS) | 0.1 | 0 | 0.1 | 0.2 | 3.5 | 7.7 | |
20 (低DS) | 0.1 | 5.5 | 0.1 | 4.7 | 3.7 | 11.4 | |
21 (檸檬酸鹽) | 0.5 | 0 | 0.1 | 0.2 | 3.1 | 6.2 | |
22 (檸檬酸鹽) | 0.5 | 5.5 | 0.1 | 2.2 | 3.2 | 7.7 | |
23 (無緩衝劑) | 0.5 | 0 | 0.1 | 0.2 | 3.2 | 6.9 | |
24 (無緩衝劑) | 0.5 | 5.5 | 0.1 | 2.3 | 3.2 | 9.3 | |
25 (NaCl) | 0.5 | 0 | 0.1 | 0.3 | 3.1 | 6.4 | |
26 (NaCl) | 0.5 | 5.5 | 0.1 | 3.4 | 3.2 | 8.9 | |
組成物編號 | 索馬魯肽(mg/ml) | 苯酚(mg/ml) | 滯後時間(小時) | |
1 (pH 7.0) | 0.5 | 0 | 42 | |
2 (pH 7.0) | 0.5 | 0.1 | 63 | |
3 (pH 7.0) | 0.5 | 5.5 | 5 | |
4 (pH 7.4) | 0.5 | 0 | >117 | |
5 (pH 7.4) | 0.5 | 0.1 | >117 | |
6 (pH 7.4) | 0.5 | 5.5 | 87 | |
7 (pH 7.8) | 0.5 | 0 | >117 | |
8 (pH 7.8) | 0.5 | 0.1 | >117 | |
9 (pH 7.8) | 0.5 | 5.5 | >117 | |
10 (pH 7.0) | 10 | 0 | 117 | |
11 (pH 7.0) | 10 | 0.1 | >117 | |
12 (pH 7.0) | 10 | 5.5 | 25 | |
13 (pH 7.4) | 10 | 0 | >117 | |
14 (pH 7.4) | 10 | 0.1 | >117 | |
15 (pH 7.4) | 10 | 5.5 | >117 | |
16 (pH 7.8) | 10 | 0 | >117 | |
17 (pH 7.8) | 10 | 0.1 | >117 | |
18 (pH 7.8) | 10 | 5.5 | >117 | |
19 (低DS) | 0.1 | 0 | >117 | |
20 (低DS) | 0.1 | 5.5 | >117 | |
21 (檸檬酸鹽) | 0.5 | 0 | >117 | |
22 (檸檬酸鹽) | 0.5 | 5.5 | >117 | |
23 (無緩衝劑) | 0.5 | 0 | >117 | |
24 (無緩衝劑) | 0.5 | 5.5 | 4 | |
25 (NaCl) | 0.5 | 0 | >117 | |
26 (NaCl) | 0.5 | 5.5 | 8 | |
儘管已在本文中說明及描述本發明之某些特徵,但一般熟習此項技術者現將想到多種修改、替代、變化及等效物。因此,應瞭解,所附申請專利範圍意欲涵蓋如屬於本發明之真實精神內的所有此類修改及變化。
無
無
Claims (15)
- 一種液體醫藥組成物,其包含索馬魯肽(semaglutide)及不超過0.01% (w/w)苯酚,其中該組成物 a.用於非經腸投予; b.為包含至少60% w/w水之水溶液;或 c.進一步包含選自由緩衝劑或等張劑組成之群的一或多種醫藥學上可接受之賦形劑。
- 如請求項1所述之組成物,其中該組成物不包含苯酚。
- 如前述請求項中任一項所述之組成物,其中該組成物為包含至少60% w/w水之水溶液。
- 如前述請求項中任一項所述之組成物,其中索馬魯肽之濃度為0.5至10 mg/ml或0.01至5 mg/ml之該組成物。
- 如前述請求項中任一項所述之組成物,其中該組成物包含一或多種醫藥學上可接受之賦形劑。
- 如請求項5所述之組成物,其中該一或多種醫藥學上可接受之賦形劑選自由緩衝劑或等張劑組成之群。
- 如前述請求項中任一項所述之組成物,其中該組成物不包含防腐劑。
- 如前述請求項中任一項所述之組成物,其中該組成物之pH值介於6.0至10.0範圍內,例如pH 7.0至7.8。
- 如前述請求項中任一項所述之組成物,其中該組成物用於非經腸投予。
- 如請求項9所述之組成物,其中該非經腸投予為皮下投予。
- 一種套組,其包含液體醫藥組成物及使用說明書,該液體醫藥組成物包含索馬魯肽及不超過0.01% (w/w)。
- 一種套組,其包含液體醫藥組成物及注射裝置,該液體醫藥組成物包含索馬魯肽及不超過0.01% (w/w)苯酚,該注射裝置用於向個體投予該組成物,其中該注射裝置選自由耐用筆及預填充筆組成之群。
- 如請求項11或12所述之套組,其中該醫藥組成物如請求項1至10中任一項所定義。
- 如前述請求項中任一項所定義之醫藥組成物,其用於醫藥。
- 如前述請求項中任一項所定義之醫藥組成物,其用於治療糖尿病或肥胖症。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP17187676.6 | 2017-08-24 | ||
EP17187676 | 2017-08-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
TW202304501A true TW202304501A (zh) | 2023-02-01 |
Family
ID=59713860
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW107129632A TWI762706B (zh) | 2017-08-24 | 2018-08-24 | Glp-1組成物及其用途 |
TW111139129A TW202304501A (zh) | 2017-08-24 | 2018-08-24 | Glp-1組成物及其用途 |
TW111110149A TWI783890B (zh) | 2017-08-24 | 2018-08-24 | Glp-1組成物及其用途 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW107129632A TWI762706B (zh) | 2017-08-24 | 2018-08-24 | Glp-1組成物及其用途 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW111110149A TWI783890B (zh) | 2017-08-24 | 2018-08-24 | Glp-1組成物及其用途 |
Country Status (19)
Country | Link |
---|---|
US (3) | US10888605B2 (zh) |
EP (2) | EP3474820B1 (zh) |
JP (1) | JP6633777B2 (zh) |
KR (1) | KR20200044016A (zh) |
CN (1) | CN111050750A (zh) |
AR (1) | AR112480A1 (zh) |
AU (1) | AU2018321157B2 (zh) |
BR (1) | BR112020002804A2 (zh) |
CA (1) | CA3082033A1 (zh) |
CL (2) | CL2020000422A1 (zh) |
CO (1) | CO2020002647A2 (zh) |
IL (1) | IL272232B1 (zh) |
MA (1) | MA46990A (zh) |
MX (1) | MX2020001525A (zh) |
PE (1) | PE20211202A1 (zh) |
PH (1) | PH12020550051A1 (zh) |
SG (1) | SG11202000940XA (zh) |
TW (3) | TWI762706B (zh) |
WO (1) | WO2019038412A1 (zh) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PE20211202A1 (es) | 2017-08-24 | 2021-07-05 | Novo Nordisk As | Composiciones de glp-1 y sus usos |
PL3746111T3 (pl) | 2018-02-02 | 2024-01-15 | Novo Nordisk A/S | Stałe kompozycje zawierające agonistę glp-1 i sól kwasu n-(8-(2- hydroksybenzoilo)amino kaprylowego i substancję poślizgową |
EP3897570A1 (en) * | 2018-12-19 | 2021-10-27 | KRKA, d.d., Novo mesto | Pharmaceutical composition comprising glp-1 analogue |
WO2020190757A1 (en) * | 2019-03-15 | 2020-09-24 | Novetide Ltd. | Improved processes for the preparation of semaglutide |
SG11202108530VA (en) * | 2019-03-15 | 2021-09-29 | Novo Nordisk As | Process for spray drying a glp-1 peptide |
CN113677702A (zh) | 2019-04-01 | 2021-11-19 | 诺和诺德股份有限公司 | 针对利拉鲁肽的抗体及其用途 |
WO2020208541A1 (en) * | 2019-04-08 | 2020-10-15 | Enzene Biosciences Limited | Composition comprising glp-1 analogue |
WO2021105393A1 (en) * | 2019-11-29 | 2021-06-03 | Novo Nordisk A/S | Processes for obtaining stable glp-1 compositions |
WO2021123228A1 (en) * | 2019-12-18 | 2021-06-24 | Krka, D.D., Novo Mesto | Pharmaceutical composition comprising glp-1 analogue |
PE20221575A1 (es) * | 2020-02-18 | 2022-10-06 | Novo Nordisk As | Formulaciones farmaceuticas |
US11478533B2 (en) | 2020-04-27 | 2022-10-25 | Novo Nordisk A/S | Semaglutide for use in medicine |
CN114146163B (zh) * | 2021-12-07 | 2023-09-26 | 苏州天马医药集团天吉生物制药有限公司 | 司美格鲁肽制剂的制备方法 |
CN114660214B (zh) * | 2022-02-18 | 2024-04-05 | 兰州积石药业有限公司 | 一种司美格鲁肽的液相色谱检测方法及其应用 |
CN116159027A (zh) * | 2022-12-29 | 2023-05-26 | 江苏诺泰澳赛诺生物制药股份有限公司 | 一种司美格鲁肽冻干药物组合物及其制备方法 |
Family Cites Families (451)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2444570A (en) | 1948-07-06 | Drive for counter numeral wheels | ||
GB735443A (en) | 1952-09-02 | 1955-08-24 | English Numbering Machines | Improvements in or relating to counting devices |
US2828742A (en) | 1957-05-02 | 1958-04-01 | American Home Prod | Cartridge-needle unit |
NL300399A (zh) | 1963-05-02 | |||
US3318289A (en) | 1965-05-11 | 1967-05-09 | Northern Ind Products | Bi-stable mechanism |
CH499734A (de) | 1968-07-19 | 1970-11-30 | Kienzle Apparate Gmbh | Klinkengesperre als Einrichtungs- und Überholkupplung |
US3758683A (en) | 1971-04-30 | 1973-09-11 | R Jackson | Insulin product |
US4282316A (en) | 1979-09-11 | 1981-08-04 | Modrovich Ivan Endre | Stabilized enzymic solutions for determining urea |
PT72703B (en) | 1980-03-21 | 1982-11-15 | Wellcome Found | Stabilised ophtalmic formulation |
US4425346A (en) | 1980-08-01 | 1984-01-10 | Smith And Nephew Associated Companies Limited | Pharmaceutical compositions |
GB2109690B (en) | 1981-02-12 | 1985-02-20 | Robert Charles Turner | Dose metering plunger devices for use with syringes |
US4568335A (en) | 1981-08-28 | 1986-02-04 | Markwell Medical Institute, Inc. | Device for the controlled infusion of medications |
DE3204178C2 (de) | 1982-02-06 | 1986-03-20 | Eppendorf Gerätebau Netheler + Hinz GmbH, 2000 Hamburg | Pipettiervorrichtung |
US4483849A (en) | 1983-01-07 | 1984-11-20 | Carter William A | Stabilization and purification of interferon with propylene glycol, resulting in a non-toxic product |
US4498788A (en) | 1983-06-03 | 1985-02-12 | Diehl Gmbh & Co. | Escapement for a timer |
EP0143895B1 (de) | 1983-09-07 | 1987-12-23 | Disetronic Ag | Tragbares Infusionsgerät |
US4468346A (en) | 1983-10-27 | 1984-08-28 | The United States Of America As Represented By The Secretary Of Agriculture | Monoclonal antibodies to porcine immunoglobulins |
JPS60129941U (ja) | 1984-02-09 | 1985-08-31 | テルモ株式会社 | 医療用器具 |
US4592745A (en) | 1984-02-29 | 1986-06-03 | Novo Industri A/S | Dispenser |
FR2583291A1 (fr) | 1985-06-14 | 1986-12-19 | Hazon Bernard | Dispositif d'avancement pas a pas du piston de seringues par double vis coaxiale avec controle du debit d'injection. application aux injections medicamenteuses intra-dermiques repetitives |
DE3546150A1 (de) | 1985-06-24 | 1987-01-22 | Hoechst Ag | Membrananker-wirkstoffkonjugat, seine herstellung sowie seine verwendung |
AU6541986A (en) | 1985-11-08 | 1987-06-02 | Disetronic A.G. | Injection instrument |
DE3609555A1 (de) | 1986-03-21 | 1987-09-24 | Josef Porner | Blutentnahmespritze |
US5120712A (en) | 1986-05-05 | 1992-06-09 | The General Hospital Corporation | Insulinotropic hormone |
US5614492A (en) | 1986-05-05 | 1997-03-25 | The General Hospital Corporation | Insulinotropic hormone GLP-1 (7-36) and uses thereof |
US5118666A (en) | 1986-05-05 | 1992-06-02 | The General Hospital Corporation | Insulinotropic hormone |
ATE110083T1 (de) | 1986-05-05 | 1994-09-15 | Gen Hospital Corp | Insulinotropes hormon. |
US4917685A (en) | 1986-05-16 | 1990-04-17 | International Minerals & Chem. Corp. | Delivery device for the administration of stabilized growth promoting hormones |
DE3638984C3 (de) | 1986-11-14 | 1993-11-18 | Haselmeier Wilhelm Fa | Injektionsgerät |
US5716990A (en) | 1987-03-09 | 1998-02-10 | Cancer Research Campaign Technology Limited | Drug delivery systems |
DK177187A (da) | 1987-04-07 | 1988-10-08 | Dcp Af 1988 As | Doseringsenhed til dosering af et antal afmaalte maengder af en vaeske, saasom insulin, fra en glasampul |
DE3715258C2 (de) | 1987-05-08 | 1996-10-31 | Haselmeier Wilhelm Fa | Injektionsgerät |
NZ224615A (en) | 1987-05-14 | 1990-04-26 | Commw Scient Ind Res Org | Process for the production of whey protein fractions |
GB8713810D0 (en) | 1987-06-12 | 1987-07-15 | Hypoguard Uk Ltd | Measured dose dispensing device |
FI883338A (fi) | 1987-07-16 | 1989-01-17 | Bristol Myers Co | Vattenloesningar av doxorubicinhydroklorid. |
IT1222331B (it) | 1987-08-25 | 1990-09-05 | Bruno Micovilovich | Siringa di sicurezza per usi parentali,a disimpegno autonomo e rapido dell'ago dopo l'uso |
US4919596A (en) | 1987-12-04 | 1990-04-24 | Pacesetter Infusion, Ltd. | Fluid delivery control and monitoring apparatus for a medication infusion system |
US4833379A (en) | 1988-01-13 | 1989-05-23 | Sherwood Medical Company | Motor control fail-safe circuit |
CH675078A5 (zh) | 1988-01-22 | 1990-08-31 | Nosta Ag | |
DE3900926C2 (de) | 1988-02-08 | 1999-05-12 | Disetronic Licensing Ag | Spritzenförmiges Injektionsgerät und Injektionsgerätebaukasten |
DK166948B1 (da) | 1988-02-10 | 1993-08-09 | Dcp Af 1988 As | Doseringsenhed til dosering af et antal afmaalte maengder af en vaeske, saasom insulin, fra en glastubule |
US4973318A (en) | 1988-02-10 | 1990-11-27 | D.C.P. Af 1988 A/S | Disposable syringe |
JPH03505401A (ja) | 1988-06-27 | 1991-11-28 | ジェネックス・コーポレーション | 組換えタンパク質の培養培地への熱放出 |
ES2069558T3 (es) | 1988-09-12 | 1995-05-16 | Graesslin Kg | Dispositivo para regular el tiempo de un reloj conmutador. |
GB8900763D0 (en) | 1989-01-13 | 1989-03-08 | Kabi Vitrum Peptide Hormones A | Multi-dose syringe |
US5216437A (en) | 1989-02-02 | 1993-06-01 | Canon Kabushiki Kaisha | Ink, and recording method making use of same |
DK68789A (da) | 1989-02-14 | 1990-08-15 | Novo Nordisk As | Injektionspen |
HU203372B (en) | 1989-02-24 | 1991-07-29 | Richter Gedeon Vegyeszet | Process for producing hyaluronic associates and pharmaceutical compositions and cosmetics comprising such active ingredient |
WO1990011296A1 (en) | 1989-03-20 | 1990-10-04 | The General Hospital Corporation | Insulinotropic hormone |
JP2822447B2 (ja) | 1989-05-19 | 1998-11-11 | 住友電気工業株式会社 | 酸化物超電導線材の製造方法および装置 |
US4994033A (en) | 1989-05-25 | 1991-02-19 | Schneider (Usa) Inc. | Intravascular drug delivery dilatation catheter |
US5226895A (en) | 1989-06-05 | 1993-07-13 | Eli Lilly And Company | Multiple dose injection pen |
DE3927286C2 (de) | 1989-08-18 | 1997-07-24 | Roehm Gmbh | Wäßrige Enzym-Flüssigformulierungen |
US5216011A (en) | 1989-09-01 | 1993-06-01 | Bristol-Myers Squibb Co. | Stable solutions of mitomycin c |
EP0431679B1 (en) | 1989-12-05 | 1994-10-19 | Merck & Co. Inc. | Method of stabilizing recombinant hepatitis B virus surface proteins from yeast |
DK17890A (da) | 1990-01-22 | 1991-07-23 | Novo Nordisk As | Fremgangsmaade og apparat til opblanding og injicering af et laegemiddel |
JP3262329B2 (ja) | 1990-01-24 | 2002-03-04 | アイ. バックレイ,ダグラス | 糖尿病治療に有用なglp―1アナログ |
US5545618A (en) | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
DE4002066A1 (de) | 1990-01-25 | 1991-08-01 | Basf Ag | Verfahren zur abtrennung von riboflavin aus fermentationssuspensionen |
GB9007113D0 (en) | 1990-03-29 | 1990-05-30 | Sams Bernard | Dispensing device |
US5207752A (en) | 1990-03-30 | 1993-05-04 | Alza Corporation | Iontophoretic drug delivery system with two-stage delivery profile |
US5318540A (en) | 1990-04-02 | 1994-06-07 | Pharmetrix Corporation | Controlled release infusion device |
US5492534A (en) | 1990-04-02 | 1996-02-20 | Pharmetrix Corporation | Controlled release portable pump |
US5226896A (en) | 1990-04-04 | 1993-07-13 | Eli Lilly And Company | Dose indicating injection pen |
IT220491Z2 (it) | 1990-04-13 | 1993-09-24 | Stilolinea Srl | Penna a sfera del tipo a punta scrivente rientrante |
EP0532546B1 (en) | 1990-05-10 | 1998-03-18 | Bechgaard International Research And Development A/S | A pharmaceutical preparation containing n-glycofurols and n-ethylene glycols |
US5257987A (en) | 1990-05-21 | 1993-11-02 | Pharmetrix Corporation | Controlled release osmotic infusion system |
DE69110290T2 (de) | 1990-09-21 | 1995-10-19 | Novo Nordisk As | Adaptor. |
US5284480A (en) | 1990-11-09 | 1994-02-08 | Medtronic, Inc. | Inflation/deflation syringe with threaded plunger |
GB9026191D0 (en) | 1990-12-01 | 1991-01-16 | Harris Pharma Ltd | Breath actuated dispensing device |
US5331954A (en) | 1990-12-21 | 1994-07-26 | Novo Nordisk A/S | Device for nasal delivery of liquid medications |
US5232706A (en) | 1990-12-31 | 1993-08-03 | Esteve Quimica, S.A. | Oral pharmaceutical preparation containing omeprazol |
AU641206B2 (en) | 1991-01-22 | 1993-09-16 | Eli Lilly And Company | Multiple dose injection pen |
DE69203472T2 (de) | 1991-02-07 | 1996-01-04 | Terumo Corp | Dosiereinrichtung für Injektor. |
US5272135A (en) | 1991-03-01 | 1993-12-21 | Chiron Ophthalmics, Inc. | Method for the stabilization of methionine-containing polypeptides |
HU222249B1 (hu) | 1991-03-08 | 2003-05-28 | Amylin Pharmaceuticals Inc. | Eljárás amilin agonista peptidszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására |
JP3070768B2 (ja) | 1991-03-27 | 2000-07-31 | ノボ ノルディスク アクティーゼルスカブ | カタラーゼ、その製法および使用 |
US5258377A (en) | 1991-04-08 | 1993-11-02 | Taiho Pharmaceutical Co., Ltd. | 2-spirocyclopropyl 4-acylcephems |
DE4112259A1 (de) | 1991-04-15 | 1992-10-22 | Medico Dev Investment Co | Injektionsgeraet |
DK68991D0 (da) | 1991-04-17 | 1991-04-17 | Novo Nordisk As | Manifold |
US5645052A (en) | 1991-04-26 | 1997-07-08 | The Boc Group Plc | Anaesthetic vaporizer with expandable/contractable reservoir for pumping liquid anaesthetic |
SE9101381D0 (sv) | 1991-05-07 | 1991-05-07 | Tomas Moks | Peptide hormone solution |
ES2074771T3 (es) | 1991-07-24 | 1995-09-16 | Medico Dev Investment Co | Inyector. |
DK175491D0 (da) | 1991-10-18 | 1991-10-18 | Novo Nordisk As | Apparat |
US5206219A (en) | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
JP3258323B2 (ja) | 1991-11-29 | 2002-02-18 | ノボ ノルディスク アクティーゼルスカブ | ペン形状をなす注射器 |
DK194291D0 (da) | 1991-11-29 | 1991-11-29 | Novo Nordisk As | Sproejte til automatisk injektion. |
US5246417A (en) | 1991-12-11 | 1993-09-21 | Alza Corporation | Indicator for iontophoresis system |
US5849700A (en) | 1991-12-20 | 1998-12-15 | Novo Nordisk A/S | Pharmaceutical formulation |
FR2686460B1 (fr) | 1992-01-20 | 1994-03-11 | Labinal Precision Mecanique | Organe de contact electrique femelle. |
US5279586A (en) | 1992-02-04 | 1994-01-18 | Becton, Dickinson And Company | Reusable medication delivery pen |
CH682968B5 (fr) | 1992-02-12 | 1994-06-30 | Rolex Montres | Procédé de fabrication d'un joint et joint pour dispositif de commande étanche pour montre obtenu selon ce procédé. |
CH682806A5 (de) | 1992-02-21 | 1993-11-30 | Medimpex Ets | Injektionsgerät. |
DE4208677A1 (de) | 1992-03-18 | 1993-09-23 | Injecta Gmbh Steinach | Injektionsvorrichtung, insbesondere fuer sehgeschaedigte diabetiker |
DK36492D0 (da) | 1992-03-19 | 1992-03-19 | Novo Nordisk As | Praeparat |
DK39892D0 (da) | 1992-03-25 | 1992-03-25 | Bernard Thorens | Peptid |
EP0632734B1 (en) | 1992-03-25 | 1998-06-10 | Tebro S.A. | Powder jet dispenser for medicament inhalation therapies |
US5271527A (en) | 1992-04-02 | 1993-12-21 | Habley Medical Technology Corporation | Reusable pharmaceutical dispenser with full stroke indicator |
US5281198A (en) | 1992-05-04 | 1994-01-25 | Habley Medical Technology Corporation | Pharmaceutical component-mixing delivery assembly |
ATE147619T1 (de) | 1992-05-13 | 1997-02-15 | Sandoz Ag | Opthalmische zusammensetzungen enthaltend ein cyclosporin |
PL176007B1 (pl) | 1992-06-15 | 1999-03-31 | Scios Inc | Nowe pochodne polipeptydu GLP-1 |
UA26190C2 (uk) | 1992-07-28 | 1999-07-19 | Сейфтек Ай Лімітед | Шприц |
GB9219849D0 (en) | 1992-09-19 | 1992-10-28 | Hypoguard Uk Ltd | Device |
SG49695A1 (en) | 1992-10-15 | 1998-06-15 | Gen Hospital Corp | An infusion pump with an electronically loadable drug library |
US5545147A (en) | 1992-10-20 | 1996-08-13 | Eli Lilly And Company | Anti-backup improvement for hypodermic syringes |
US5378233A (en) | 1992-11-18 | 1995-01-03 | Habley Medical Technology Corporation | Selected dose pharmaceutical dispenser |
US5320609A (en) | 1992-12-07 | 1994-06-14 | Habley Medical Technology Corporation | Automatic pharmaceutical dispensing syringe |
GB9226423D0 (en) | 1992-12-18 | 1993-02-10 | Sams Bernard | Incrementing mechanisms |
JPH08506749A (ja) | 1993-02-19 | 1996-07-23 | メディコル ホールディング ソシエテ アノニム | 液体および無菌医薬物質を保管し、かつ移すための、予め充填された注射器 |
US5383865A (en) | 1993-03-15 | 1995-01-24 | Eli Lilly And Company | Medication dispensing device |
ZA941881B (en) | 1993-04-02 | 1995-09-18 | Lilly Co Eli | Manifold medication injection apparatus and method |
US5584815A (en) | 1993-04-02 | 1996-12-17 | Eli Lilly And Company | Multi-cartridge medication injection device |
US6284727B1 (en) | 1993-04-07 | 2001-09-04 | Scios, Inc. | Prolonged delivery of peptides |
SE9301494D0 (sv) | 1993-04-30 | 1993-04-30 | Kabi Pharmacia Ab | A device for dosing liquid preparation |
DK52393D0 (zh) | 1993-05-05 | 1993-05-05 | Novo Nordisk As | |
WO1995005848A1 (en) | 1993-08-24 | 1995-03-02 | Novo Nordisk A/S | Protracted glp-1 |
EP0792290B1 (en) | 1993-09-17 | 2001-08-29 | Novo Nordisk A/S | Acylated insulin |
GB9320782D0 (en) | 1993-10-08 | 1993-12-01 | Univ Leeds Innovations Ltd | Stabilising of proteins on solution |
PT729362E (pt) | 1993-11-19 | 2000-06-30 | Searle & Co | Composicao transdermica de n-¬n-¬5-¬4-(aminoiminometil)fenil|-1oxopentil|-l-alfa-aspartil|-l-fenillalanina ou esteres e seus sais farmaceuticamente aceitaveis |
US5705483A (en) | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
US5478316A (en) | 1994-02-02 | 1995-12-26 | Becton, Dickinson And Company | Automatic self-injection device |
US5514097A (en) | 1994-02-14 | 1996-05-07 | Genentech, Inc. | Self administered injection pen apparatus and method |
US5562623A (en) | 1994-02-14 | 1996-10-08 | Univec | Single-use syringe assembly including spring clip lock and plunger |
AU1847695A (en) | 1994-02-22 | 1995-09-04 | Syntex-Synergen Neuroscience Joint Venture, The | Pharmaceutical formulations of cntf |
CA2189542A1 (en) | 1994-05-03 | 1995-11-09 | Karen M. Oxenbýll | Alkaline glucose oxidase |
GB9409496D0 (en) | 1994-05-12 | 1994-06-29 | London Health Ass | Method for improving glycaemic control in diabetes |
US5750140A (en) | 1994-05-20 | 1998-05-12 | Novo Nordisk A/S | Transdermal delivery of tiagabine |
US5652216A (en) | 1994-05-26 | 1997-07-29 | Novo Nordisk A/S | Pharmaceutical preparation |
CA2197671A1 (en) | 1994-06-15 | 1995-12-21 | Hubert Menendez | Locking device for syringe or like instrument |
US5461031A (en) | 1994-06-16 | 1995-10-24 | Eli Lilly And Company | Monomeric insulin analog formulations |
US5827232A (en) | 1994-06-22 | 1998-10-27 | Becton Dickinson And Company | Quick connect medication delivery pen |
US5725508A (en) | 1994-06-22 | 1998-03-10 | Becton Dickinson And Company | Quick connect medication delivery pen |
US5440976A (en) | 1994-08-23 | 1995-08-15 | Fred Giuliano | Adjustable dispensing stirrer for soluble sweeteners |
US5823998A (en) | 1994-08-24 | 1998-10-20 | Eli Lilly Japan Kabushiki Kaisha | Injection apparatus |
US5549574A (en) | 1994-08-30 | 1996-08-27 | Eli Lilly And Company | Cartridge assembly for use in a pen-type medicament injector |
US5574008A (en) | 1994-08-30 | 1996-11-12 | Eli Lilly And Company | Biologically active fragments of glucagon-like insulinotropic peptide |
ES2211889T3 (es) | 1994-08-31 | 2004-07-16 | Mitsubishi Pharma Corporation | Procedimiento para la purificacion de albumina de suero recombinante. |
CN1157553A (zh) | 1994-09-09 | 1997-08-20 | 诺沃挪第克公司 | 清洁、消毒和防护隐形眼镜的方法 |
US5549575A (en) | 1994-09-13 | 1996-08-27 | Becton Dickinson And Company | Cartridge retainer assembly for medication delivery pen |
US5582598A (en) | 1994-09-19 | 1996-12-10 | Becton Dickinson And Company | Medication delivery pen with variable increment dose scale |
BR9508847A (pt) | 1994-09-20 | 1999-11-30 | Novo Nordisk A S E Slagterisel | Processo para tratar uma solução aquosa de proteìna e para produzir um gênero alimentìcio à base de carne, mistura de solução de proteìna/hidrolisado tratada com calor, ou hidrolisado lìquido tratado com calor, gênero alimentìcio à base de carne e uso da mistura de solução de proteìna/hidrolisado tratada com calor, ou de hidrolisado lìquido tratado com calor |
ZA958073B (en) | 1994-09-28 | 1996-04-23 | Anthony William Manicom | Method of and apparatus for administering a drug to a patient |
US5512549A (en) | 1994-10-18 | 1996-04-30 | Eli Lilly And Company | Glucagon-like insulinotropic peptide analogs, compositions, and methods of use |
WO1996020005A1 (en) | 1994-12-23 | 1996-07-04 | Novo Nordisk A/S | Protracted glp-1 compositions |
ES2329528T3 (es) | 1995-02-03 | 2009-11-26 | Novozymes A/S | Metodo para diseñar mutantes alfa-amilasa con propiedades determinadas. |
JP2000510813A (ja) | 1995-02-06 | 2000-08-22 | ジェネテイックス・インスティテュート・インコーポレイテッド | Il−12用処方 |
GB9503969D0 (en) | 1995-02-28 | 1995-04-19 | Sams Bernard | Incrementing mechanism |
CA2213682C (en) | 1995-03-07 | 2009-10-06 | Eli Lilly And Company | Recyclable medication dispensing device |
US5869602A (en) | 1995-03-17 | 1999-02-09 | Novo Nordisk A/S | Peptide derivatives |
CA2215694A1 (en) | 1995-03-17 | 1996-09-26 | Novo Nordisk A/S | Insulin derivatives |
US6184201B1 (en) | 1995-04-14 | 2001-02-06 | Nps Allelix Corp. | Intestinotrophic glucagon-like peptide-2 analogs |
US5834428A (en) | 1995-04-14 | 1998-11-10 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
CN1114613C (zh) | 1995-06-02 | 2003-07-16 | 诺沃奇梅兹有限公司 | 蛋白质溶液的铝/铁处理和膜浓缩方法 |
EP0840628B1 (en) | 1995-06-02 | 2002-05-08 | Novo Nordisk A/S | Automatic withdrawal of piston rod |
US5631347A (en) | 1995-06-07 | 1997-05-20 | Eli Lilly And Company | Reducing gelation of a fatty acid-acylated protein |
BR9608857A (pt) | 1995-06-13 | 1999-06-15 | Novo Nordisk As | Composição líquida e detergente líquida |
US5674204A (en) | 1995-09-19 | 1997-10-07 | Becton Dickinson And Company | Medication delivery pen cap actuated dose delivery clutch |
US5688251A (en) | 1995-09-19 | 1997-11-18 | Becton Dickinson And Company | Cartridge loading and priming mechanism for a pen injector |
JP3060287B2 (ja) | 1995-10-09 | 2000-07-10 | 参天製薬株式会社 | アパファントを主薬とする水性点眼剤 |
US5899879A (en) | 1995-12-19 | 1999-05-04 | Genesis Medical Technologies, Inc. | Spring-actuated needleless injector |
RU2181299C2 (ru) | 1996-02-23 | 2002-04-20 | Ново Нордиск А/С | Шприц с электронным представлением параметров |
KR100441821B1 (ko) | 1996-03-05 | 2004-10-15 | 구르뉘 로베르 | 완충화된오르토에스테르중합체를함유하는약학조성물 |
UA35653C2 (uk) | 1996-03-12 | 2001-04-16 | Ново Нордіск А/С | Пристрій для ін'єкцій |
US6086567A (en) | 1996-04-02 | 2000-07-11 | Disetronic Licensing Ag | Injection device |
JP2001527435A (ja) | 1996-04-24 | 2001-12-25 | ノボ ノルディスク アクティーゼルスカブ | 注射針 |
DE122010000020I1 (de) | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
ATE241997T1 (de) | 1996-07-03 | 2003-06-15 | Alza Corp | Nicht-waessrige protische peptidzubereitungen |
US5932547A (en) | 1996-07-03 | 1999-08-03 | Alza Corporation | Non-aqueous polar aprotic peptide formulations |
CA2258491A1 (en) | 1996-07-05 | 1998-01-15 | Novo Nordisk A/S | Automatic needle insertion mechanism |
JP4187794B2 (ja) | 1996-07-05 | 2008-11-26 | ノボ ノルディスク アクティーゼルスカブ | 用量設定装置 |
PL330757A1 (en) | 1996-07-05 | 1999-05-24 | Novo Nordisk As | Elastic piston rod |
US5981489A (en) | 1996-07-18 | 1999-11-09 | Alza Corporation | Non-aqueous protic peptide formulations |
US5962407A (en) | 1996-07-26 | 1999-10-05 | Kelly; Michael T. | Loloatin derivatives and analogs |
JP2001501593A (ja) | 1996-08-08 | 2001-02-06 | アミリン・ファーマシューティカルズ,インコーポレイテッド | 胃腸運動を調節するための方法 |
JPH10101696A (ja) | 1996-08-08 | 1998-04-21 | Shinotesuto:Kk | 形質転換体にて発現される蛋白質に含まれる夾雑物質の除去方法及び精製蛋白質 |
US6956026B2 (en) | 1997-01-07 | 2005-10-18 | Amylin Pharmaceuticals, Inc. | Use of exendins for the reduction of food intake |
US5709662A (en) | 1996-08-23 | 1998-01-20 | Becton Dickinson France, S.A. | Cartridge for an injection device |
US5843036A (en) | 1996-08-23 | 1998-12-01 | Becton Dickinson And Company | Non-dosing cartridge for an injection device |
US6458924B2 (en) | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
US6268343B1 (en) | 1996-08-30 | 2001-07-31 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
US6277819B1 (en) | 1996-08-30 | 2001-08-21 | Eli Lilly And Company | Use of GLP-1 or analogs in treatment of myocardial infarction |
UA72181C2 (uk) | 1996-08-30 | 2005-02-15 | Ново Нордіск А/С | Похідна глюкагоноподібного пептиду-1 (варіанти), фармацевтична композиція та спосіб одержання лікувального засобу (варіанти), спосіб лікування діабету (варіанти) і ожиріння |
US6006753A (en) | 1996-08-30 | 1999-12-28 | Eli Lilly And Company | Use of GLP-1 or analogs to abolish catabolic changes after surgery |
US7235627B2 (en) | 1996-08-30 | 2007-06-26 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
UA49912C2 (uk) | 1996-09-13 | 2002-10-15 | Ново Нордіск А/С | Шприц для ін'єкцій |
US6110149A (en) | 1996-09-13 | 2000-08-29 | Novo Nordisk A/S | Syringe |
US5947934A (en) | 1996-09-13 | 1999-09-07 | Novo Nordisk A/S | Dose display for an injection syringe |
US6379339B1 (en) | 1996-09-13 | 2002-04-30 | Nova Nordisk A/S | Syringe |
PT927055E (pt) | 1996-09-20 | 2002-05-31 | Novo Nordisk As | Cilindro de manobra |
US6146361A (en) | 1996-09-26 | 2000-11-14 | Becton Dickinson And Company | Medication delivery pen having a 31 gauge needle |
US5908830A (en) | 1996-10-31 | 1999-06-01 | Merck & Co., Inc. | Combination therapy for the treatment of diabetes and obesity |
UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
TW524667B (en) | 1996-12-05 | 2003-03-21 | Pfizer | Parasiticidal pyrazoles |
US5954689A (en) | 1996-12-20 | 1999-09-21 | Novo Nordisk A/S | Jet injector |
US7312196B2 (en) | 1997-01-08 | 2007-12-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
US6136784A (en) | 1997-01-08 | 2000-10-24 | Amylin Pharmaceuticals, Inc. | Amylin agonist pharmaceutical compositions containing insulin |
TW503113B (en) | 1997-01-16 | 2002-09-21 | Senju Pharma Co | Aqueous suspension for nasal administration |
US6274553B1 (en) | 1997-01-20 | 2001-08-14 | Japan Energy Corporation | Method for stabilizing peptides and freeze-dried medicinal compositions containing peptides obtained by using the method |
GB2321419B (en) | 1997-01-27 | 2001-02-07 | Medic Aid Ltd | Atomizer |
AU5652098A (en) | 1997-02-04 | 1998-08-25 | Novo Nordisk A/S | A device for the administration of a liquid medicament suspension |
DE29703820U1 (de) | 1997-03-03 | 1998-07-02 | Medico Dev Investment Co | Injektionsgerät |
US5898028A (en) | 1997-03-20 | 1999-04-27 | Novo Nordisk A/S | Method for producing powder formulation comprising an insulin |
US20010020155A1 (en) | 1997-03-25 | 2001-09-06 | Soren Mikkelsen | Injection system |
WO1998043658A1 (en) | 1997-03-31 | 1998-10-08 | Eli Lilly And Company | Glucagon-like peptide-1 analogs |
CA2236519C (en) | 1997-05-02 | 2011-09-13 | 1149336 Ontario Inc. | Methods of enhancing functioning of the large intestine |
US7101853B2 (en) | 1997-05-06 | 2006-09-05 | Amylin Pharmaceuticals, Inc. | Method for treating or preventing gastritis using amylin or amylin agonists |
RU2111019C1 (ru) | 1997-05-22 | 1998-05-20 | Сергей Александрович Хворостов | Универсальный инъектор |
HU227800B1 (en) | 1997-05-23 | 2012-03-28 | Predrag Sikiric | New bpc peptide salts with organo-protective activity, the process for their preparation and their use in therapy |
US7910548B2 (en) | 1997-06-06 | 2011-03-22 | Amylin Pharmaceuticals, Inc. | Methods for treating obesity |
US6003736A (en) | 1997-06-09 | 1999-12-21 | Novo Nordisk A/S | Device for controlled dispensing of a dose of a liquid contained in a cartridge |
WO1998056381A1 (en) | 1997-06-09 | 1998-12-17 | Bridge Pharma, Inc. | Compounds with combined antihistaminic and mast cell stabilizing activities, intended for ophthalmic use |
US6074372A (en) | 1997-06-09 | 2000-06-13 | Novo Nordisk A/S | Dose setting mechanism and an injection syringe having such a dose setting mechanism |
ZA984697B (en) | 1997-06-13 | 1999-12-01 | Lilly Co Eli | Stable insulin formulations. |
US6796970B1 (en) | 1997-06-17 | 2004-09-28 | Novo Nordisk A/S | Dose setting device |
US5961496A (en) | 1997-06-17 | 1999-10-05 | Novo Nordisk A/S | Syringe with tiltable nut for quick piston disengagement |
JP3503129B2 (ja) | 1997-06-30 | 2004-03-02 | 荒川化学工業株式会社 | カラーフィルタ層用剥離剤およびカラーフィルタ用ガラス基板の再生方法 |
AU7331598A (en) | 1997-07-11 | 1999-02-08 | Novo Nordisk A/S | An apparatus for the registration of the setting of a medical device |
EP0996476B1 (en) | 1997-07-14 | 2003-05-21 | Novo Nordisk A/S | Cylinder ampoule |
AU8333398A (en) | 1997-07-14 | 1999-02-10 | Novo Nordisk A/S | Injection member |
DE19730999C1 (de) | 1997-07-18 | 1998-12-10 | Disetronic Licensing Ag | Dosierknopfsicherung an einer Vorrichtung zur dosierten Verabreichung eines injizierbaren Produkts |
US5957896A (en) | 1997-08-11 | 1999-09-28 | Becton, Dickinson And Company | Medication delivery pen |
FR2767479B1 (fr) | 1997-08-22 | 1999-10-22 | Aguettant Lab | Dispositif d'injection de medicament |
WO1999016485A1 (en) | 1997-09-29 | 1999-04-08 | Becton Dickinson And Company | Injection device and drug cartridge for preventing cross-use of the device and drug cartridge |
EP1029536B1 (en) | 1997-10-01 | 2007-11-28 | Novadel Pharma Inc. | Buccal non-polar spray |
CN1240718C (zh) | 1997-10-24 | 2006-02-08 | 诺沃挪第克公司 | 人胰岛素衍生物的聚集体 |
ATE237636T1 (de) | 1997-10-24 | 2003-05-15 | Genentech Inc | Reinigung von molekülen |
US6312413B1 (en) | 1997-10-30 | 2001-11-06 | Novo Nordisk A/S | Cylinder ampoule |
EP1049486A4 (en) | 1997-12-05 | 2006-01-04 | Lilly Co Eli | GLP-1 FORMULATIONS |
ZA9811127B (en) | 1997-12-09 | 2000-07-11 | Lilly Co Eli | Stabilized teriparatide solutions. |
DE29721752U1 (de) | 1997-12-09 | 1998-02-12 | Siemens Ag | Crimpkontakt für Stecksysteme |
US6380357B2 (en) | 1997-12-16 | 2002-04-30 | Eli Lilly And Company | Glucagon-like peptide-1 crystals |
JPH11249087A (ja) | 1997-12-18 | 1999-09-17 | Tome:Kk | コンタクトレンズ用液剤 |
WO1999034764A2 (en) | 1998-01-09 | 1999-07-15 | Amylin Pharmaceuticals, Inc. | Amylin agonist pharmaceutical compositions containing insulin |
JP4353544B2 (ja) | 1998-01-09 | 2009-10-28 | アミリン・ファーマシューティカルズ,インコーポレイテッド | アミリン作動薬ペプチド用製剤 |
CN1198937C (zh) | 1998-01-30 | 2005-04-27 | 第一三得利制药株式会社 | 利用辅助肽制造肽的方法 |
EP1003581B1 (en) | 1998-01-30 | 2000-11-08 | Novo Nordisk A/S | An injection syringe |
CA2320993C (en) | 1998-02-13 | 2008-05-06 | Graham Francois Duirs | Drug delivery system |
ATE366115T1 (de) | 1998-02-13 | 2007-07-15 | Amylin Pharmaceuticals Inc | Inotropische und diuretische effekte von exendin und glp-1 |
CA2320962C (en) | 1998-02-13 | 2011-04-19 | Amylin Pharmaceuticals, Inc. | Novel mixed amylin activity compounds |
US5961495A (en) | 1998-02-20 | 1999-10-05 | Becton, Dickinson And Company | Medication delivery pen having a priming mechanism |
US6221053B1 (en) | 1998-02-20 | 2001-04-24 | Becton, Dickinson And Company | Multi-featured medication delivery pen |
US6248095B1 (en) | 1998-02-23 | 2001-06-19 | Becton, Dickinson And Company | Low-cost medication delivery pen |
ATE466027T1 (de) | 1998-02-27 | 2010-05-15 | Novo Nordisk As | Abkömmlinge von glp-1 analogen |
EP1062240B1 (en) | 1998-02-27 | 2010-04-28 | Novo Nordisk A/S | N-terminally modified glp-1 derivatives |
DE69916811T2 (de) | 1998-02-27 | 2005-04-14 | Novo Nordisk A/S | Glp-1 derivate mit einem helix-gehalt über 25 %, die partiell strukturierte mizellenartige aggregate bilden |
EP1056774A1 (en) | 1998-02-27 | 2000-12-06 | Novo Nordisk A/S | N-terminally truncated glp-1 derivatives |
WO1999043708A1 (en) | 1998-02-27 | 1999-09-02 | Novo Nordisk A/S | Glp-1 derivatives of glp-1 and exendin with protracted profile of action |
DE69918070T2 (de) | 1998-03-13 | 2005-08-25 | Novo Nordisk A/S | Stabilisierte, wässrige Glukagonlösungen, enthaltend Detergenzien |
JP4072319B2 (ja) | 1998-03-13 | 2008-04-09 | ノヴォ ノルディスク アクティーゼルスカブ | 安定化水溶性ペプチド溶液 |
WO1999057566A1 (en) | 1998-05-01 | 1999-11-11 | The University Of Tennessee Research Corporation | Flow cytometric characterization of amyloid fibrils |
CA2332314A1 (en) | 1998-06-11 | 1999-12-16 | Cerus Corporation | Use of alkylating compounds for inhibiting proliferation of arterial smooth muscle cells |
WO2000002605A1 (en) | 1998-07-08 | 2000-01-20 | Novo Nordisk A/S | A medical delivery device and a cartridge assembly for use in the same |
BR9913857A (pt) | 1998-09-17 | 2001-06-12 | Lilly Co Eli | Formulações de proteìna |
US6033376A (en) | 1998-09-30 | 2000-03-07 | Allergan Sales, Inc. | Wound shaper sleeve |
US6489292B1 (en) | 1998-11-18 | 2002-12-03 | Novo Nordisk A/S | Stable aqueous insulin preparations without phenol and cresol |
US6605067B1 (en) | 1998-11-20 | 2003-08-12 | Novo Nordisk A/S | Injection needle |
US6375975B1 (en) | 1998-12-21 | 2002-04-23 | Generex Pharmaceuticals Incorporated | Pharmaceutical compositions for buccal and pulmonary application |
AU2373400A (en) | 1998-12-22 | 2000-07-12 | Eli Lilly And Company | Shelf-stable formulation of glucagon-like peptide-1 |
DE29900482U1 (de) | 1999-01-14 | 2000-08-31 | Medico Dev Investment Co | Injektionsgerät |
JP4426727B2 (ja) | 1999-01-14 | 2010-03-03 | アミリン・ファーマシューティカルズ,インコーポレイテッド | 新規なエキセンジンアゴニスト製剤とその投与方法 |
ATE390960T1 (de) | 1999-02-14 | 2008-04-15 | Pfeiffer Erich Gmbh & Co Kg | Spender für fliessfähige medien |
US6258062B1 (en) | 1999-02-25 | 2001-07-10 | Joseph M. Thielen | Enclosed container power supply for a needleless injector |
US6444788B1 (en) | 1999-03-15 | 2002-09-03 | Novo Nordisk A/S | Ion exchange chromatography of GLP-1, analogs and derivatives thereof |
EP1163211B1 (en) | 1999-03-17 | 2008-09-24 | Novo Nordisk A/S | Method for acylating peptides and proteins |
SE9901366D0 (sv) | 1999-04-16 | 1999-04-16 | Pharmacia & Upjohn Ab | Injector device and method for its operation |
FR2793684B1 (fr) | 1999-05-17 | 2001-08-10 | Ethypharm Lab Prod Ethiques | Utilisation de microspheres biodegradables liberant un agent anticancereux pour le traitement du glioblastome, procede de preparation de ces microspheres et suspension les contenant |
US6506724B1 (en) | 1999-06-01 | 2003-01-14 | Amylin Pharmaceuticals, Inc. | Use of exendins and agonists thereof for the treatment of gestational diabetes mellitus |
EP1207753A4 (en) | 1999-06-17 | 2005-11-30 | Univ California | PRESERVATION OF ORGANS BY CONTINUOUS CARDIAC PERFUSION WITH PEG-HB FOR IMPROVED PRESERVATION IN HYPOTHERMIA |
WO2000078333A2 (en) | 1999-06-21 | 2000-12-28 | Eli Lilly And Company | Synergetic use of thiazolidinediones with glucagon-like peptide-1 and agonists thereof to treat non-insulin dependant diabetes |
WO2001000223A2 (en) | 1999-06-25 | 2001-01-04 | Minimed Inc. | Multiple agent diabetes therapy |
PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
EP1076066A1 (en) | 1999-07-12 | 2001-02-14 | Zealand Pharmaceuticals A/S | Peptides for lowering blood glucose levels |
AU6892100A (en) | 1999-08-05 | 2001-03-05 | Becton Dickinson & Company | Medication delivery pen |
TW453884B (en) | 1999-09-16 | 2001-09-11 | Novo Nordisk As | Dose setting limiter |
WO2001021198A1 (en) | 1999-09-20 | 2001-03-29 | Eli Lilly And Company | Method for reducing the risk of cancer |
US6514230B1 (en) | 1999-10-12 | 2003-02-04 | Novo Nordisk A/S | Air shot mechanism for electronic injection devices |
US6569832B1 (en) | 1999-11-12 | 2003-05-27 | Novo Nordisk A/S | Inhibition of beta cell degeneration |
US7022674B2 (en) | 1999-12-16 | 2006-04-04 | Eli Lilly And Company | Polypeptide compositions with improved stability |
PT1242121E (pt) | 1999-12-16 | 2005-05-31 | Lilly Co Eli | Composicoes polipeptidicas com estabilidade melhorada |
GB9930882D0 (en) | 1999-12-30 | 2000-02-23 | Nps Allelix Corp | GLP-2 formulations |
AU2353701A (en) | 2000-01-11 | 2001-07-24 | Novo Nordisk A/S | Transepithelial delivery of glp-1 derivatives |
AU2001220765A1 (en) | 2000-01-24 | 2001-07-31 | Medtronic Minimed, Inc. | Mixed buffer system for stabilizing polypeptide formulations |
US7598222B2 (en) | 2000-01-27 | 2009-10-06 | Eli Lilly And Company | Process for solubilizing glucagon-like peptide 1 compounds |
EP1396499A3 (en) | 2000-01-27 | 2004-12-29 | Eli Lilly And Company | Process for solubilizing glucagon-like peptide 1 (GLP-1) compounds |
US6569901B2 (en) | 2000-01-28 | 2003-05-27 | Novo Nordisk A/S | Alkynyl-substituted propionic acid derivatives, their preparation and use |
US6844321B2 (en) | 2000-01-31 | 2005-01-18 | Novo Nordisk A/S | Crystallization of a GLP-1 analogue |
GB0007071D0 (en) | 2000-03-24 | 2000-05-17 | Sams Bernard | One-way clutch mechanisms and injector devices |
WO2001077141A1 (en) | 2000-04-06 | 2001-10-18 | Novo Nordisk A/S | Shock heat treatment of polypeptides |
US6692472B2 (en) | 2000-05-04 | 2004-02-17 | Novo Nordisk A/S | Injection device, a preassembled dose setting and injection mechanism for an injection device, and a method of assembling an injection device |
CA2380423A1 (en) | 2000-05-17 | 2001-11-22 | Bionebraska, Inc. | Peptide pharmaceutical formulations |
US6716198B2 (en) | 2000-05-18 | 2004-04-06 | Novo Nordisk A/S | Injection device |
US6547763B2 (en) | 2000-05-18 | 2003-04-15 | Novo Nordisk A/S | Dose display for injection device |
US6547764B2 (en) | 2000-05-31 | 2003-04-15 | Novo Nordisk A/S | Double pointed injection needle |
DE60124710T2 (de) | 2000-06-16 | 2007-09-13 | Eli Lilly And Co., Indianapolis | Analoge des glucagon ähnlichen peptid-1 |
US6663602B2 (en) | 2000-06-16 | 2003-12-16 | Novo Nordisk A/S | Injection device |
US6369419B1 (en) | 2000-06-23 | 2002-04-09 | International Business Machines Corporation | Self-aligned near surface strap for high density trench DRAMS |
US6613019B2 (en) | 2000-07-14 | 2003-09-02 | Novo Nordisk A/S | Liquid medication delivery device and a method of delivering an intended dose |
WO2002024257A1 (en) | 2000-09-22 | 2002-03-28 | Novo Nordisk A/S | A medication delivery device |
JP4798833B2 (ja) | 2000-10-24 | 2011-10-19 | 一般財団法人化学及血清療法研究所 | 加熱処理工程を含むヒト血清アルブミンの製造方法 |
SI1724284T1 (sl) | 2000-12-07 | 2009-12-31 | Lilly Co Eli | Glp-1 fuzijski proteini |
US7199217B2 (en) | 2000-12-13 | 2007-04-03 | Eli Lilly And Company | Amidated glucagon-like peptide-1 |
MXPA03005135A (es) | 2000-12-13 | 2003-12-04 | Lilly Co Eli | Regimen de tratamiento cronico usando peptidos insulinotropicos similares al glucagon. |
US20020151467A1 (en) | 2000-12-21 | 2002-10-17 | Leung Frank K. | Methods and compositions for oral insulin delivery |
US6899699B2 (en) | 2001-01-05 | 2005-05-31 | Novo Nordisk A/S | Automatic injection device with reset feature |
GB2371227A (en) | 2001-01-10 | 2002-07-24 | Grandis Biotech Gmbh | Crystallisation - resistant aqueous growth hormone formulations |
EP2319565A3 (en) | 2001-02-14 | 2013-07-17 | Novo Nordisk A/S | Electronically controlled device |
JP4280070B2 (ja) | 2001-02-16 | 2009-06-17 | コンジュケム バイオテクノロジーズ インコーポレイテッド | 胃腸疾患および胃腸障害の処置のための長期持続性グルカゴン様ペプチド2(glp−2) |
WO2002069994A2 (en) | 2001-03-07 | 2002-09-12 | Novo Nordisk A/S | Combined use of derivatives of glp-1 analogs and ppar ligands |
US6573237B2 (en) | 2001-03-16 | 2003-06-03 | Eli Lilly And Company | Protein formulations |
EP2258425B1 (en) | 2001-05-16 | 2013-01-30 | Eli Lilly and Company | Medication injector apparatus |
US20040156835A1 (en) | 2001-05-30 | 2004-08-12 | Taiji Imoto | Protein preparation |
GB0113881D0 (en) | 2001-06-07 | 2001-08-01 | Innovate Biomed Ltd | Foil cutting system |
EP1412384B1 (en) | 2001-06-28 | 2007-12-26 | Novo Nordisk A/S | Stable formulation of modified glp-1 |
US6872705B2 (en) | 2001-07-13 | 2005-03-29 | Allergan, Inc. | Use of antimicrobial peptides as preservatives in ophthalmic preparations, including solutions, emulsions, and suspensions |
DE10163326A1 (de) | 2001-07-30 | 2003-02-27 | Disetronic Licensing Ag | Verabreichungsgerät mit Dosiervorrichtung |
CN1335182A (zh) | 2001-08-08 | 2002-02-13 | 华中科技大学 | 胰岛素口腔喷剂及其制备工艺 |
WO2003020201A2 (en) | 2001-08-28 | 2003-03-13 | Eli Lilly And Company | Pre-mixes of glp-1 and basal insulin |
US6676641B2 (en) | 2001-09-05 | 2004-01-13 | Futura Medical Technologies, Inc. | Retractable hypodermic syringe |
KR20040054729A (ko) | 2001-10-18 | 2004-06-25 | 브리스톨-마이어스 스큅 컴퍼니 | 인간 글루카곤-유사-펩티드-1 모방체, 및 당뇨병 및 이와관련된 증상의 치료에 있어서 이의 용도 |
US7179788B2 (en) | 2001-10-19 | 2007-02-20 | Eli Lilly And Company | Biphasic mixtures of GLP-1 and insulin |
ES2614603T3 (es) | 2002-02-20 | 2017-06-01 | Emisphere Technologies, Inc. | Procedimiento de administración de moléculas GLP-1 |
AU2003209475A1 (en) | 2002-03-07 | 2003-09-16 | Vectura Limited | Fast melt multiparticulate formulations for oral delivery |
US7462596B2 (en) | 2002-03-15 | 2008-12-09 | Natimmune A/S | Pharmaceutical compositions comprising mannose binding lectin |
EP1494704A1 (en) | 2002-04-04 | 2005-01-12 | Novo Nordisk A/S | Glp-1 agonist and cardiovascular complications |
CN1665540A (zh) | 2002-07-09 | 2005-09-07 | 桑多斯股份公司 | 含1,2-丙二醇的高浓度人生长激素液体制剂 |
US6945961B2 (en) | 2002-07-10 | 2005-09-20 | Novo Nordisk A/S | Injection device |
JP2005532129A (ja) | 2002-07-10 | 2005-10-27 | ノボ・ノルデイスク・エー/エス | 投与量設定リミッタを備える注入器 |
EP1391794A1 (en) | 2002-07-23 | 2004-02-25 | Novo Nordisk A/S | Device with time indicating means |
WO2004020026A1 (en) | 2002-08-29 | 2004-03-11 | Novo Nordisk A/S | Frontloaded injection device |
EP1542744B1 (en) | 2002-09-24 | 2009-06-24 | SHL Group AB | Injecting device |
ATE397620T1 (de) | 2002-09-25 | 2008-06-15 | Novo Nordisk As | Aufreinigungsverfahren, das eine mikrofiltration bei erhöhten temperaturen beinhaltet |
US7273921B2 (en) | 2002-09-25 | 2007-09-25 | Novo Nordisk A/S | Method for producing acylated peptides |
AU2003278929A1 (en) | 2002-10-18 | 2004-05-13 | Amylin Pharmaceuticals, Inc. | Treatment of pancreatitis with amylin |
US6969702B2 (en) | 2002-11-20 | 2005-11-29 | Neuronova Ab | Compounds and methods for increasing neurogenesis |
WO2004056313A2 (en) | 2002-12-17 | 2004-07-08 | Amylin Pharmaceuticals, Inc. | Prevention and treatment of cardiac arrhythmias |
WO2004066939A2 (en) | 2003-01-27 | 2004-08-12 | Sarnoff Corporation | Controlled-release drug delivery system |
GB0304822D0 (en) | 2003-03-03 | 2003-04-09 | Dca Internat Ltd | Improvements in and relating to a pen-type injector |
GB0304823D0 (en) | 2003-03-03 | 2003-04-09 | Dca Internat Ltd | Improvements in and relating to a pen-type injector |
GB0304824D0 (en) | 2003-03-03 | 2003-04-09 | Dca Internat Ltd | Improvements in and relating to a pen-type injector |
GB0306642D0 (en) | 2003-03-22 | 2003-04-30 | Dca Design Int Ltd | Improvements in and relating to an injector for a medical product |
GB0308267D0 (en) | 2003-04-10 | 2003-05-14 | Dca Design Int Ltd | Improvements in and relating to a pen-type injector |
WO2004089985A1 (en) | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | Stable pharmaceutical compositions |
US8008255B2 (en) | 2003-05-30 | 2011-08-30 | Amylin Pharmaceuticals, Inc. | Methods and compositions for enhanced transmucosal delivery of peptides and proteins |
CN1812807A (zh) * | 2003-06-03 | 2006-08-02 | 诺沃挪第克公司 | 稳定化的药物肽组合物 |
CN102940879B (zh) * | 2003-06-03 | 2017-06-06 | 诺沃挪第克公司 | 稳定化的药物肽组合物 |
CA2527743A1 (en) | 2003-06-03 | 2004-12-09 | Novo Nordisk A/S | Stabilized pharmaceutical peptide compositions |
WO2005018721A1 (en) | 2003-08-12 | 2005-03-03 | Eli Lilly And Company | Medication dispensing apparatus with triple screw threads for mechanical advantage |
US20070275877A1 (en) | 2003-08-29 | 2007-11-29 | Amylin Pharmaceuticals, Inc. | Methods for Treating or Ameliorating Ghrelin-Associated Diseases and Disorders |
EP2932981B1 (en) | 2003-09-19 | 2021-06-16 | Novo Nordisk A/S | Albumin-binding derivatives of GLP-1 |
PE20050444A1 (es) | 2003-10-31 | 2005-08-09 | Takeda Pharmaceutical | Compuestos de piridina como inhibidores de la peptidasa |
ATE447412T1 (de) | 2003-11-04 | 2009-11-15 | Novartis Vaccines & Diagnostic | Antagonist-anti-cd40-monoklonale antikörper und anwendungsverfahren |
KR101520209B1 (ko) | 2003-11-06 | 2015-05-13 | 시애틀 지네틱스, 인크. | 리간드에 접합될 수 있는 모노메틸발린 화합물 |
WO2005046716A1 (en) | 2003-11-13 | 2005-05-26 | Novo Nordisk A/S | Soluble pharmaceutical compositions for parenteral administration comprising a glp-1 peptide and a insulin peptide of short time action for treatment of diabetes and bulimia |
US20060287221A1 (en) | 2003-11-13 | 2006-12-21 | Novo Nordisk A/S | Soluble pharmaceutical compositions for parenteral administration comprising a GLP-1 peptide and an insulin peptide of short time action for treatment of diabetes and bulimia |
CN104826116A (zh) | 2003-11-20 | 2015-08-12 | 诺沃挪第克公司 | 对于生产和用于注射装置中是最佳的含有丙二醇的肽制剂 |
AR047776A1 (es) | 2003-12-16 | 2006-02-22 | Sod Conseils Rech Applic | Composiciones farmaceuticas glp - 1 |
US20060286129A1 (en) | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
US20050143303A1 (en) | 2003-12-26 | 2005-06-30 | Nastech Pharmaceutical Company Inc. | Intranasal administration of glucose-regulating peptides |
ATE471340T1 (de) | 2004-02-11 | 2010-07-15 | Amylin Pharmaceuticals Inc | Peptide der amylin familie, verfahren zu deren herstellung und verwendung |
EP1765406A4 (en) | 2004-05-21 | 2012-11-28 | Mediplex Corp | ADDITIVES FOR IMPROVED MUCOSAL ABSORPTION OF THERAPEUTIC AGENTS |
US7448385B2 (en) | 2004-06-07 | 2008-11-11 | Purepharm Inc. | Nasal adaptation of an oral inhaler device |
US8410047B2 (en) | 2004-06-11 | 2013-04-02 | Novo Nordisk A/S | Counteracting drug-induced obesity using GLP-1 agonists |
WO2006000567A2 (en) | 2004-06-28 | 2006-01-05 | Novo Nordisk A/S | Use of glp-1 receptor agonists and / or dpp-iv inhibitors in combination with proton pump inhibitors and ppar agonists for the preparation of a medicament for the treatment of diabetes type i i and impaired pancreatic beta-cell function |
EP1789075A4 (en) | 2004-08-25 | 2009-07-01 | Uab Research Foundation | ABSORPTION ENHANCER FOR DRUG ADMINISTRATION |
EP2286838A3 (en) | 2004-11-01 | 2013-09-04 | Amylin Pharmaceuticals, LLC | Treatment of obesity and related disorders |
CN101056650A (zh) | 2004-11-12 | 2007-10-17 | 诺和诺德公司 | 促胰岛素肽的稳定制剂 |
US20090011976A1 (en) | 2004-11-12 | 2009-01-08 | Novo Nordisk A/S | Stable Formulations Of Peptides |
EA200701065A1 (ru) | 2004-11-16 | 2007-12-28 | Элан Фарма Интернэшнл Лтд. | Инъецируемые составы, содержащие нанодисперсный оланзапин |
US7833707B2 (en) | 2004-12-30 | 2010-11-16 | Boehringer Ingelheim Vetmedica, Inc. | Methods of overexpression and recovery of porcine circovirus type 2 ORF2 |
ES2633917T3 (es) | 2005-01-21 | 2017-09-26 | Novo Nordisk A/S | Dispositivo de inyección automático con un mecanismo de liberación superior |
CA2600836A1 (en) | 2005-03-08 | 2006-09-14 | Pharmacia & Upjohn Company Llc | Composition comprising an antibody against macrophage colony-stimulating factor (m-csf) and a chelating agent |
US8834891B2 (en) | 2005-03-14 | 2014-09-16 | Boehringer Ingelheim Vetmedica, Inc. | Immunogenic compositions comprising Lawsonia intracellularis |
TWI362392B (en) | 2005-03-18 | 2012-04-21 | Novo Nordisk As | Acylated glp-1 compounds |
WO2007014051A2 (en) | 2005-07-22 | 2007-02-01 | Amylin Pharmaceuticals, Inc. | Use of amylin and amylin agonists as cardioprotective or myoprotective agents |
WO2007022518A2 (en) | 2005-08-19 | 2007-02-22 | Amylin Pharmaceuticals, Inc. | New uses of glucoregulatory proteins |
EP1978926A2 (en) | 2005-12-19 | 2008-10-15 | Comentis, Inc. | Topical mecamylamine formulations for ocular administration and uses thereof |
DK2371385T3 (en) | 2005-12-29 | 2015-11-30 | Boehringer Ingelheim Vetmed | Use of a PV2 immunogen composition for reduction of clinical symptoms in pigs |
EP2015769A4 (en) | 2006-04-13 | 2013-12-25 | Ipsen Pharma | PHARMACEUTICAL COMPOSITIONS OF HGLP-1, EXENDINE 4 AND THEIR ANALOGUES |
TW200821386A (en) | 2006-07-18 | 2008-05-16 | Centocor Inc | Human GLP-1 mimetibodies, compositions, methods and uses |
TWI489984B (zh) | 2006-08-04 | 2015-07-01 | Wyeth Corp | 用於非經腸道傳輸化合物之配方及其用途 |
TW200843794A (en) | 2006-12-21 | 2008-11-16 | Centocor Inc | Use of long-acting GLP-1 receptor agonists to improve insulin sensitivity and lipid profiles |
GB0704846D0 (en) | 2007-03-13 | 2007-04-18 | Futura Medical Dev Ltd | Topical pharmaceutical formulation |
AU2008244523B2 (en) | 2007-04-23 | 2012-02-16 | Intarcia Therapeutics, Inc. | Suspension formulations of insulinotropic peptides and uses thereof |
EP2190460B1 (en) | 2007-09-05 | 2014-12-17 | Novo Nordisk A/S | Peptides derivatized with a-b-c-d- and their therapeutical use |
US20100210559A1 (en) | 2007-09-11 | 2010-08-19 | Mondobiotech Laboratories Ag | Trap-14 as a therapeutic agent |
WO2009051992A1 (en) | 2007-10-19 | 2009-04-23 | Bausch & Lomb Incorporated | Compositions and methods for treating diseases involving ocular angiogenesis by inhibiting one or more selected receptor tyrosine kinases |
MX2010005345A (es) | 2007-11-14 | 2010-08-31 | Amylin Pharmaceuticals Inc | Metodos para el tratamiento de la obesidad y enfermedades y trastornos relacionados con la obesidad. |
US20090186819A1 (en) | 2007-12-11 | 2009-07-23 | Marieve Carrier | Formulation of insulinotropic peptide conjugates |
EP2340261B1 (en) | 2008-10-21 | 2017-12-20 | Novo Nordisk A/S | Amylin derivatives |
WO2010107874A2 (en) | 2009-03-17 | 2010-09-23 | Amylin Pharmaceuticals, Inc. | Methods for affecting body composition using amylin agonists |
EP2437816B1 (en) | 2009-06-04 | 2013-04-24 | Novo Nordisk Health Care AG | Mixing device with piston coupling arrangement |
SG178195A1 (en) | 2009-07-31 | 2012-03-29 | Sanofi Aventis Deutschland | Long acting insulin composition |
MX2012001399A (es) | 2009-07-31 | 2012-03-21 | Sanofi Aventis Deutschland | Profarmacos que comprenden un conjugado de insulina-conector. |
WO2011050008A2 (en) | 2009-10-19 | 2011-04-28 | Amylin Pharmaceuticals, Inc. | Combination therapy comprising administration of an amylinomimetic and a pyy peptidomimetic for effecting weight loss and for treating obesity and related metabolic conditions and disorders |
NZ601109A (en) | 2009-12-10 | 2014-06-27 | Merck Patent Gmbh | Pharmaceutical composition comprising oligopeptides, preferably cilengitide |
CA2784757A1 (en) | 2009-12-16 | 2011-07-07 | Novo Nordisk A/S | Double-acylated glp-1 derivatives |
WO2011104378A1 (en) | 2010-02-26 | 2011-09-01 | Novo Nordisk A/S | Peptides for treatment of obesity |
WO2011109784A1 (en) | 2010-03-05 | 2011-09-09 | Conjuchem, Llc | Formulation of insulinotropic peptide conjugates |
WO2011109787A1 (en) | 2010-03-05 | 2011-09-09 | Conjuchem, Llc | Methods of administering insulinotropic peptides |
RU2559320C2 (ru) | 2010-03-26 | 2015-08-10 | Ново Нордиск А/С | Новые аналоги глюкагона |
KR20130101005A (ko) | 2010-07-28 | 2013-09-12 | 아밀린 파마슈티칼스, 엘엘씨. | 안정화된 영역을 갖는 glp-1 수용체 효능제 화합물 |
EP2438930A1 (en) | 2010-09-17 | 2012-04-11 | Sanofi-Aventis Deutschland GmbH | Prodrugs comprising an exendin linker conjugate |
WO2012062803A1 (en) | 2010-11-09 | 2012-05-18 | Novo Nordisk A/S | Double-acylated glp-1 derivatives |
EP2665469A1 (en) | 2011-01-19 | 2013-11-27 | Novo Nordisk A/S | Glp-1 compositions |
BR112013019734A2 (pt) | 2011-02-04 | 2016-10-25 | Biocopea Ltd | composições e métodos para tratar inflamação crônica e doenças inflamatórias |
US20130035281A1 (en) | 2011-02-09 | 2013-02-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
ES2612278T3 (es) | 2011-04-12 | 2017-05-16 | Novo Nordisk A/S | Derivados de GLP-1 doble-acilados |
UA116189C2 (uk) | 2011-05-02 | 2018-02-26 | Мілленніум Фармасьютікалз, Інк. | КОМПОЗИЦІЯ АНТИ-α4β7 АНТИТІЛА |
JP2014519509A (ja) | 2011-06-10 | 2014-08-14 | ノヴォ ノルディスク アー/エス | ポリペプチド |
CN103957926B (zh) | 2011-07-08 | 2018-07-03 | 安米林药品有限责任公司 | 具有增强的作用持续时间和降低的免疫原性的工程改造的多肽 |
US9132170B2 (en) | 2011-07-29 | 2015-09-15 | Case Western Reserve University | Compositions and methods for treating cognitive deficits |
ES2626013T3 (es) | 2011-09-06 | 2017-07-21 | Novo Nordisk A/S | Derivados de GLP-1 |
TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對bcma之e3以及cd3的結合分子 |
JP2015500823A (ja) | 2011-12-09 | 2015-01-08 | ノヴォ ノルディスク アー/エス | Glp−1アゴニスト |
ES2810153T3 (es) | 2012-03-01 | 2021-03-08 | Novo Nordisk As | Profármacos de GLP-1 |
CN102579350B (zh) | 2012-03-02 | 2013-04-24 | 海南灵康制药有限公司 | 右旋布洛芬脂质体固体制剂 |
CA2868398A1 (en) | 2012-04-02 | 2013-10-10 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
EP2841089A4 (en) | 2012-04-03 | 2016-03-16 | Univ Boston | COMPOSITIONS, PROCESSES AND ASSAYS WITH AMYLIN OR AMLYANANALOGA FOR ABETA PEPTIDE-MEDIATED ILLNESSES |
JP6227629B2 (ja) | 2012-04-19 | 2017-11-08 | ノヴォ ノルディスク アー/エス | ヒトアミリン類似体 |
US11274135B2 (en) | 2012-05-08 | 2022-03-15 | Novo Nordisk A/S | Double-acylated GLP-1 derivatives |
US10000542B2 (en) | 2012-05-08 | 2018-06-19 | Novo Nordisk A/S | Double-acylated GLP-1 derivatives |
US20150174209A1 (en) | 2012-05-25 | 2015-06-25 | Amylin Pharmaceuticals. Llc | Insulin-pramlintide compositions and methods for making and using them |
SI2861608T1 (sl) | 2012-06-19 | 2019-08-30 | Debiopharm International Sa | Derivati predzdravila (E)-N-metil-N-((3-metilbenzofuran-2-IL)metil)- 3-(7-okso-5,6,7,8-tetrahidro-1 ,8-nafthiridin-3-il)akrilamid |
AU2013286177B2 (en) | 2012-07-01 | 2018-04-26 | Novo Nordisk A/S | Use of long-acting GLP-1 peptides |
CN104717972A (zh) * | 2012-10-17 | 2015-06-17 | 诺和诺德A/S(股份有限公司) | 用于口服肽递送的脂肪酸酰化氨基酸 |
PL2970389T3 (pl) | 2013-03-15 | 2021-03-08 | Rhythm Pharmaceuticals, Inc. | Kompozycje farmaceutyczne |
PT2991671T (pt) | 2013-05-02 | 2018-11-05 | Novo Nordisk As | Dosagem oral de compostos de glp-1 |
EP2994128B1 (en) | 2013-05-10 | 2019-01-30 | Gilead Apollo, LLC | Acc inhibitors and uses thereof |
EP3010531A1 (en) | 2013-06-21 | 2016-04-27 | Novo Nordisk A/S | Novel uses of glp-1 receptor agonists in patients treated with insulin and/or suffering from type 1 diabetes |
EP3016975B1 (en) | 2013-07-04 | 2019-01-16 | Novo Nordisk A/S | Derivatives of glp-1 like peptides, and uses thereof |
JO3425B1 (ar) | 2013-07-15 | 2019-10-20 | Novartis Ag | مشتقات البابيريدينيل-اندول واستخدامها كعامل متمم لمثبطات b |
CN103405753B (zh) * | 2013-08-13 | 2016-05-11 | 上海仁会生物制药股份有限公司 | 稳定的促胰岛素分泌肽水针药物组合物 |
WO2015155151A1 (en) | 2014-04-07 | 2015-10-15 | Novo Nordisk A/S | Double-acylated glp-1 compounds |
AU2015280110A1 (en) | 2014-06-25 | 2017-01-12 | Glaxosmithkline Llc | Pharmaceutical compositions |
WO2016001862A1 (en) | 2014-07-04 | 2016-01-07 | Wockhardt Limited | Extended release formulations of insulins |
WO2016038521A1 (en) | 2014-09-08 | 2016-03-17 | Sun Pharmaceutical Industries Limited | Pharmaceutical compositions of liraglutide |
JP6730278B2 (ja) * | 2014-11-27 | 2020-07-29 | ノヴォ ノルディスク アー/エス | Glp−1誘導体及びその使用 |
CN105777872B (zh) * | 2014-12-16 | 2019-06-07 | 深圳翰宇药业股份有限公司 | 一种萨摩鲁肽的纯化方法 |
CN107249620B (zh) | 2015-05-13 | 2018-06-26 | 杭州九源基因工程有限公司 | 一种包含glp-1类似物的药物制剂及其制备方法 |
TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重glp-1/升糖素受體促效劑之新毒蜥外泌肽(exendin-4)衍生物 |
ES2835033T3 (es) | 2016-03-03 | 2021-06-21 | Novo Nordisk As | Derivados de GLP-1 y sus usos |
RU2768283C2 (ru) | 2016-04-28 | 2022-03-23 | Ново Нордиск А/С | Семаглутид при сердечно-сосудистых состояниях |
US20190374613A1 (en) | 2016-11-22 | 2019-12-12 | Biocon Research Limited | Pharmaceutical compositions of glp-1 analogues |
GB201621987D0 (en) | 2016-12-22 | 2017-02-08 | Archer Virgil L See Archer Sheri A Arecor Ltd | Novel composition |
JP2020514407A (ja) | 2017-01-24 | 2020-05-21 | マクリーゲン, インク.Macregen, Inc. | アポリポプロテイン模倣物を用いる加齢黄斑変性と他の眼疾患の治療 |
PE20211202A1 (es) | 2017-08-24 | 2021-07-05 | Novo Nordisk As | Composiciones de glp-1 y sus usos |
EP3727332A1 (en) | 2017-12-21 | 2020-10-28 | Sanofi | Liquid pharmaceutical composition |
TWI705820B (zh) | 2018-06-22 | 2020-10-01 | 美商美國禮來大藥廠 | Gip/glp1促效劑組合物 |
KR20210024082A (ko) | 2018-06-25 | 2021-03-04 | 제이씨알 파마 가부시키가이샤 | 단백질 함유 수성 액제 |
PE20221575A1 (es) | 2020-02-18 | 2022-10-06 | Novo Nordisk As | Formulaciones farmaceuticas |
-
2018
- 2018-08-24 PE PE2020000202A patent/PE20211202A1/es unknown
- 2018-08-24 WO PCT/EP2018/072835 patent/WO2019038412A1/en unknown
- 2018-08-24 TW TW107129632A patent/TWI762706B/zh active
- 2018-08-24 TW TW111139129A patent/TW202304501A/zh unknown
- 2018-08-24 MA MA046990A patent/MA46990A/fr unknown
- 2018-08-24 CN CN201880054209.2A patent/CN111050750A/zh active Pending
- 2018-08-24 KR KR1020207006965A patent/KR20200044016A/ko active IP Right Grant
- 2018-08-24 AR ARP180102424 patent/AR112480A1/es unknown
- 2018-08-24 JP JP2018561585A patent/JP6633777B2/ja active Active
- 2018-08-24 EP EP18756449.7A patent/EP3474820B1/en active Active
- 2018-08-24 BR BR112020002804-5A patent/BR112020002804A2/pt unknown
- 2018-08-24 AU AU2018321157A patent/AU2018321157B2/en active Active
- 2018-08-24 TW TW111110149A patent/TWI783890B/zh active
- 2018-08-24 MX MX2020001525A patent/MX2020001525A/es unknown
- 2018-08-24 SG SG11202000940XA patent/SG11202000940XA/en unknown
- 2018-08-24 CA CA3082033A patent/CA3082033A1/en active Pending
- 2018-08-24 EP EP24155461.7A patent/EP4360651A2/en active Pending
-
2020
- 2020-01-24 IL IL272232A patent/IL272232B1/en unknown
- 2020-01-28 US US16/774,666 patent/US10888605B2/en active Active
- 2020-02-07 PH PH12020550051A patent/PH12020550051A1/en unknown
- 2020-02-20 CL CL2020000422A patent/CL2020000422A1/es unknown
- 2020-03-09 CO CONC2020/0002647A patent/CO2020002647A2/es unknown
- 2020-12-08 US US17/115,773 patent/US11752198B2/en active Active
-
2021
- 2021-05-31 CL CL2021001430A patent/CL2021001430A1/es unknown
-
2023
- 2023-07-26 US US18/226,405 patent/US20240016896A1/en active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI783890B (zh) | Glp-1組成物及其用途 | |
JP7422754B2 (ja) | 安定性セマグルチド組成物およびその使用 | |
JP2023116778A (ja) | 補体活性のモジュレータ | |
WO2021144477A1 (en) | Glp-1 compositions and uses thereof | |
CN113226368A (zh) | 采用齐鲁考普的神经疾病治疗 | |
RU2777600C2 (ru) | Композиции на основе glp-1 и пути их применения | |
RU2803237C2 (ru) | Стабильные композиции на основе семаглутида и их варианты применения | |
JP2022547906A (ja) | 細胞死を阻害する化合物 | |
TW202410917A (zh) | 澱粉素類似物之液體調配物 | |
EP4319798A1 (en) | Liquid formulations of amylin analogues |