S4.E3. 造浪者與其重要的藥物成就 Our pioneers

 

百靈佳殷格翰在1885年成立後不久，就憑藉著遠見、耐心和創新點子，致力於改善人類和動物的健康！而一路走來有需多的造浪者與我們一同前進。

Farsightedness, patience, and ideas: Soon after the company was founded in 1885, men and women pursuing research at Boehringer Ingelheim were already working on improving human and animal health. These are just a few of our outstanding pioneers.

 

ALBERT BOEHRINGER

百靈佳殷格翰的創辦人Albert Boehringer (1861–1939) 在德國慕尼黑主修化學，因為擁有成為企業家的夢想，他購入了一間酒石酸製造廠（tartar factory），但很快的他就發現，要發展酒石酸（tartaric acid）事業有一定的困難度；西元1893年，Albert 嘗試用黴菌生產檸檬酸，不過因為他們使用了木質桶（應使用無菌桶）導致細菌滋生，而非原本期待的黴菌，最終只生產出乳酸（lactic acid），這項實驗也就以失敗收場。

但Albert 將這項失敗的實驗轉化為商業成功的基礎：自1895年起量產乳酸；直到1905年，百靈佳殷格翰開始發展藥劑化學產品：生物鹼；而這一切的資金來源就是來自乳酸事業。

 

Boehringer (1861–1939) studied chemistry in Munich. But soon he finds himself seized with the desire to become an entrepreneur. He becomes the owner of a tartar factory. The tartaric acid business proves to be difficult, however. Boehringer looks for new products and in 1893 attempts to use mold to produce citric acid. His experiment fails: His wooden vats are not sterile, and bacteria displace the mold, leaving behind lactic acid. Albert Boehringer turns this failed experiment into a commercial success and begins to produce large quantities of lactic acid in 1895. By 1905, the revenue from this business has provided the financial foundations needed to embark on the industrial production of pharmaceutical chemicals: alkaloids.

 

 

PROF. DR. HEINRICH WIELAND

Wieland（1877–1957）博士，生物化學家；他在1903年與百靈佳殷格翰的創辦人 Albert Boehringer 一起工作。在 Wieland 的協助之下，Albert 於1917 年成立了公司的第一個科學部門。

Wieland 也促進了心血管疾病藥物 cadechol^®科德孝，以及lobelin^®的發展（該藥物用於處理呼吸驟停或休克等緊急狀況）。Heinrich Wieland 對膽汁酸（bile acid）以及相關物質研究的貢獻，也讓他在1927 年獲頒諾貝爾化學獎。

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Wieland (1877–1957), a biochemist, begins to work with his cousin Albert Boehringer in 1903. Thanks to Wieland, Albert Boehringer establishes the company’s first science department in 1917. His work results in the development of the cardiovascular medicine cadechol^® as well as lobelin^®, an emergency treatment for respiratory arrest and other shock conditions. In 1927, Heinrich Wieland is awarded the Nobel Prize for his research into the composition of bile acid.

 

 

DR . JOANNE VAN RYN

Joanne van Ryn 博士，於1992 年加入百靈佳殷格翰團隊。

她從2008 年開始鑽研抗凝血劑 Pradaxa^®普栓達的反轉方法；Pradaxa^®普栓達可藉由減少血液凝固，進而預防高危險性血栓阻塞事件（如：中風）；但同時，抗凝血劑也可能會造成於意外（像是交通事故）緊急搶救時不必要的出血。在短短七年內，Joanne van Ryn 博士與她來自各領域的團隊夥伴們，成功讓反轉劑 Praxbind^®達栓普問世。如今 Praxbind^®達栓普已在多個國家／區域銷售，為病患提供更多性命保障。

 

The Canadian scientist joined Boehringer Ingelheim in 1992.

Starting in 2008, she began thinking of ways to reverse the anticoagulant pradaxa^®, which helps to prevent dangerous thromboembolic events like stroke by reducing blood clotting. However, this may also lead to unnecessary bleeding during emergencies, such as a traffic accident. In just seven years, van Ryn and her team from mutiple disciplines were able to introduce the reversal agent praxbind^® to the market. Today, praxbind^® is available in many countries, bringing further value to patients.

 

 

DR. GEORG SCHEUING

身為百靈佳殷格翰科學部的負責人，Scheuing 博士（1895-1949），在1924年時，便成功提高了乳酸的產量，甚至完成了山梗菜生物鹼（alkaloids lobeline）、茶鹼（theophylline）和咖啡因的混和生產。在他完成該項創舉前，山梗菜生物鹼等物質，皆只能從植物中提煉。

我們也以Scheuing 博士之名成立美因茲大學Georg Scheuing 基金會（Mainz University Georg Scheuing Foundation），並每年贊助化學系和醫學系學生持續於科學上成長。

 

As head of Boehringer Ingelheim’s Science Department, from 1924 Scheuing (1895–1949) not only improves the production of lactic acid but also achieves synthetic production of the alkaloids lobeline, theophylline and caffeine. Until then, it was necessary to extract them from plants.

Mainz University’s Georg Scheuing Foundation continues to support chemistry and pharmacy students every year, until today.

 

 

DR. NORBERT HAUEL

Norbert Hauel 博士於1979 年至2015 年，都在百靈佳殷格翰藥物化學部門任職。

Hauel 博士與他的團隊發現了一種強效，並能持續降低血壓的活性物質： Telmisartan。該物質於西元1998  年取得首批銷售許可，命名為Micardis^®必康平錠。Hauel 亦參與抗凝血劑研究的分子設計（molecule design）。該項研究促成Pradaxa^®普栓達問世，於西元2008年成為市面上首個活性物質類（active substance class）藥物。

 

The head of Boehringer Ingelheim’s Medicinal Chemistry group worked at the company from 1979 to 2015.

Together with his team, Hauel discovers an active substance that has a strong and very long-lasting reduction in blood pressure: telmisartan. The active substance is awarded its first marketing authorization in 1998 as micardis^®. Hauel also participates in molecule design in the field of anticoagulant research. This finally gives rise to pradaxa^®, which comes onto the market in 2008 as the first medicine in its active substance class.

 

 

DR. KNUT ELBERS

Knut Elbers 博士本身為生物學家，擔任百靈佳殷格翰的歐洲動物疫苗研究部主管長達9年的時間，他現在是百靈佳殷格翰位於奧地利茵斯布魯克（Innsbruck）子公司 ViraTherapeutics 的常務董事。

Elbers博士專攻人類溶瘤病毒療法（oncolytic virus therapies for humans）（免疫療法之一），參與多項開發專案，包含牛隻活性疫苗：Bovela^®。自2015年，Bovela^®疫苗已經成為牛隻的防護罩，令牠們免受傳染性極強的牛病毒性下痢（bovine virus diarrhea，BVD）危害。

 

The biologist led Boehringer Ingelheim’s European Animal Health Vaccine Research organization for a period of nine years. He is now Managing Director of ViraTherapeutics, a Boehringer Ingelheim subsidiary in Innsbruck, Austria, and works on oncolytic virus therapies for humans.

During his work for the corporation, Elbers was involved in several important development projects. These include the development of a live vaccine for cattle: bovela^®. Since 2015, bovela^® has helped to protect these animals against bovine virus diarrhea (BVD), a widespread condition.

 

 

DR. ROLF BANHOLZER

Rolf Banholzer 是一名化學博士，他在1960年代就加入公司位於殷格翰的藥物化學／科學部（Science Department for Medicinal Chemistry），現在擔任實驗室負責人。

Banholzer 博士主攻如Atropine、Seopotamine、Atrovent^®定喘樂、Oxivent^®、Flubron 等藥物分子的合成與性質研究。他的主要發現之一是Tiotropium bromide，該藥物於2002年首次獲准上市，名稱為Spiriva^®適喘樂。活性物質Tiotropium bromide 成為慢性阻塞性肺病（chronic obstructive pulmonary disease，簡稱COPD）治療的黃金標準（gold standard），用以幫助世界各地的COPD 患者。

 

The doctor of chemistry joined the company’s Science Department for Medicinal Chemistry at its Ingelheim site in 1960, as head of the laboratory. He works on the synthesis and properties of molecules such as atropine, seopotamine, atrovent^®, oxivent^® and flubron. One of his major discoveries is tiotropium bromide, which is approved as spiriva^® for the first time in 2002. This active substance becomes the gold standard for respiratory therapy for chronic obstructive pulmonary disease (COPD) and helps patients worldwide.

 

 

DR. OTTO THOMÄ

身為一名化學家，Otto Thoma 博士（1901-1993）以活性物質異丙腎上腺素（Isoprenaline）為基礎開發了氣喘藥物Aludrin^®，這是一種對性命安危至關重要的腎上腺素衍生物（adrenalin derivative）藥物，並於1941年問市。

Thoma博士本身對魚類過敏，在偶然的機會下，他將異丙腎上腺素製滑石粉撲在自己的皮膚上，發現了這款活性物質除了對氣喘有效，也能舒緩皮膚的搔癢感；並以此為基礎，後續產出藥劑Ingelan^®，於1947年上市，為百靈佳殷格翰在第二次世界大戰後上市的第一項產品。

 

The chemist (1901–1993) develops the first highly effective asthma medicine aludrin^®, which was introduced in 1941. This is based on the active substance isoprenaline, an adrenalin derivative which is essential for life. By chance,

Thomä also discovered a second indication for this active ingredient; he suffered from a fish allergy and used an isoprenaline talcum powder to powder his skin. He noticed that the active substance relieved his itchiness. In 1947, the resulting medicine ingelan^® was Boehringer Ingelheim’s first product launch after the World War II.

 

 

DR. JOHN PARK

這位癌症生物學家於2001年投入呼吸研究（respiratory research）時，便已設定了非常明確的目標：特發性纖維化（idiopathic pulmonary fibrosis，簡稱IPF）。Park 博士運用相關經驗，與癌症研究的同仁們密切合作，成功開發以有效成份nintedanib為基底的藥劑：Ofev^®抑肺纖。

Ofev^®抑肺纖能有效減緩病情惡化，被美國食品藥品監督管理局（Food and Drug Administration，FDA）認證為突破性治療藥物，並於2014年成為第一個取得上市資格的IPF 藥品。

 

When the cancer biologist embarks on respiratory research in 2001, his goal is clear: to combat idiopathic pulmonary fibrosis. This chronic, progressive pulmonary disease had received scant attention in medical research at that time. Park, who had joined Boehringer Ingelheim in 1994, drew upon his experience and close relationships with his colleagues in cancer research and applied this to pulmonary fibrosis. His team succeeded in developing the medicine ofev^®, based on the active ingredient nintedanib.

ofev^® effectively slows progression of the disease; it was awarded FDA breakthrough status and soon thereafter its first market authorization in 2014.

 

 

DR. TIMOTHY LEARD

Leard 博士已經在百靈佳殷格翰工作了22年；這位美國籍博士率領他的團隊研發、並且推動第一個用在治療狗狗癌症的疫苗：Oncept^®，於2009年取得上市許可。

Oncept^® 的抗原原本被設定為用於治療人類，對Leard 博士來說（目前擔任百靈佳殷格翰免疫療法研發部，以及動物健康事業全球生物計畫負責人），這代表動物健康可以從人類藥物研究中獲益，反之亦然。

 

Leard has worked for the Boehringer Ingelheim Group for 22 years; together with his team, the American developed, tested and licensed the first vaccine for the treatment of cancer in dogs, oncept^®, that has been approved since 2009.

This antigen was originally designed for treating in humans. For Leard, who is now Head of Research and Development for immune therapies as well as Global Biologicals Project Leader in Boehringer Ingelheim’s animal health business, this demonstrates how animal health can benefit from human pharmaceuticals research, and vice versa.

 

 

HANNS STROBEL

Hanns Strobel（1888-1954）是一名受過嚴謹訓練的藥劑師，他主張：藥劑師、化學家、商人應該儘早開始交流，如此勢必能對藥物研發有所助益（it would be helpful for the development of medicines if pharmacists, chemists, physicians and businessmen talked to one another early on.）。

Strobel 於1922年加入百靈佳殷格翰，很快地成為藥物專業部門的負責人。他優化了公司的產品線，引入嚴格的科學標準，為現在依然穩健運作中的製藥業務，奠定了扎實的基礎。

 

The trained pharmacist (1888–1954) realizes that it would be helpful for the development of medicines if pharmacists, chemists, physicians and businessmen talked to one another early on.

Strobel joins Boehringer Ingelheim in 1922 and subsequently becomes head of its Pharmaceutical Specialties Department. He optimizes the company’s product pipeline and introduces stringent scientific standards, thus laying the foundations for the modern pharmaceuticals business.

 

 

DR. GERALD NABOZNY

Nabozny 博士與他的團隊自2007年開始尋找因應介白素23（interleukin-23）的抗體；Il23會導致發炎性皮膚病（乾癬）。

Nabozny 團隊研發出Risankizumab，也是百靈佳殷格翰所推出的首例治療性抗體。2016年，百靈佳殷格翰與製藥公司Abbvie 艾伯維合作，Risankizumab 於2019年獲准上市成為乾癬治療用藥。

 

In 2007, Nabozny and his teammates begin to search for an antibody against interleukin-23. Interleukin-23 triggers the inflammation in psoriasis.

Their research pays off: risankizumab is the first therapeutic antibody developed by Boehringer Ingelheim. In 2016, Boehringer Ingelheim enters into a partnership with the pharmaceutical company AbbVie. In 2019, AbbVie obtains market authorization for this medicine, for the treatment of psoriasis.

 

 

DR. VINCENT J. MERLUZZI

Merluzzi 於1986年加入美國百靈佳殷格翰；這位專攻免疫學和病毒學的研究員，於1980年代末期開始從事愛滋病（AIDS）研究。在發現Nevirapine奈委拉平（一種來自新型物質的HIV抑制劑，能阻止HIV-1病毒的複製）之後，Merluzzi 團隊成功地推動藥品Viramune^®衛滋的開發。1996年，美國食品藥品監督管理局（FDA）加速核准了Viramune^®衛滋的上市許可，與其他抗病毒藥物（Antiretroviral drugs）同列為HIV-1治療藥物。這項創舉明顯的改善HIV-1患者的治療。

百靈佳殷格翰藉由2000年展開的Viramune^®衛滋捐贈計劃，幫助了許多發展中國家：提供孕期感染HIV-1的孕婦Viramune^®衛滋，挽救成千上晚的嬰兒免於愛滋感染。

 

Merluzzi joined Boehringer Ingelheim in the US in 1986. The researcher, who focuses on immunology and virology, began doing his research on AIDS at the end of the 1980s. This was followed by the discovery of nevirapine, an HIV inhibitor from a new class of substances that blocks the replication of HIV-1 viruses. Within only a short period of time, Merluzzi and his team succeeded in advancing the development of viramune^® (nevirapine). In 1996, the FDA granted viramune^® marketing approval in an accelerated approval procedure as a combination therapy with other antiretroviral drugs for the treatment of HIV-1 infections. This significantly improved the treatment of HIV-1 patients.

With the viramune^® donation program, which started in 2000, Boehringer Ingelheim provided assistance in developing countries for many years: By giving viramune^® to HIV-1-infected pregnant women during childbirth, thousands of children were saved from being born infected with AIDS.

 

 

DR. MARTIN WOLF

可尼丁（clonidine）曾被視為製作感冒藥的有效成分（active ingredient），但在實驗初期，就發現它會降低實驗者的血壓以及減慢心率。Wolf 博士（1915-1997）於1962年時，為了密切研究可尼丁的降血壓效果，將自己當作實驗對象。他的研究成功奠定Catapres^®降保適藥物研發的基礎； Catapres^®降保適如今依然是高血壓治療用藥。

 

The active ingredient clonidine was originally intended for use as a cold remedy. But in its very first trials it also lowered the trial participants’ blood pressure and slowed their heart rate. Wolf (1915–1997), a clinical research scientist, subsequently decided in 1962 to take a closer look at clonidine’s blood pressure-reducing effect by testing it on himself. His successful research laid the foundations for the medicine catapresan^®, which is still used today for the treatment of high blood pressure.