Translational Research and Commercialization of a Novel Herbal Transdermal Patch for the Adjuvant Treatment of Rheumatoid Arthritis

用於輔助性治療類風濕關節炎的新穎透皮給藥貼之轉化研究及產物化

Student thesis: Doctoral Thesis

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Author(s)

  • Pok Yu Augustine CHOW

Detail(s)

Awarding Institution
Supervisors/Advisors
Award date30 Aug 2012

Abstract

The translation of biomedical discoveries into treatments for inflammatory diseases, cancer, neurodegenerative diseases or heart diseases for the benefits of improving our lives is now considered a potential solution to the disparity between basic research and its benefits to the society. In 2005, when a herbal antagonist of TNF-α, called H-179, was first identified by means of proprietary drug discovery and screening technology – HerboChip® in an enriched fraction of Andrographis paniculata (Acanthaceae), the author of this dissertation intended to adopt the then-frontier translation approach to conduct a research and development of this herbal extract with the ultimate goal of commercializing it into a pragmatic medical treatment for rheumatoid arthritis (RA), which is one of the most commonly seen inflammatory diseases affliciting the global aging populations. In order to achieve this goal, a novel conceptual framework of rapid commercialization for technological innovations is introduced and applied to the development of this active pharmaceutical ingredient (API) H-179 into a transdermal patch in form of cataplasm in the most cost-effective manner possible and has eventually accomplished a marketable cataplasm for the relief of RA symptom. It is estimated that this cataplasm H-179 will have a potential market value reaching RMB 1 billion dollar in 5 years after the market launch.

Based on previous preclinical studies using in vitro as well as well-accepted in vivo animal model, it has been demonstrated that the API developed – H-179 – for the treatment of RA is not only safe but also effective in relieving pain and inflammation. A preliminary clinical study investigating the potential benefits of H-179 for the treatment of RA patients was then undertaken at the medical school of Zhongshan University and the results confirmed the safety and efficacy of this API.

In present study, further development was carried out in transdermal drug delivery system and succeeded in developing an effective and easy-to-use dosage form – a cataplasm for H-179. Firstly, manufacturing process of H-179 cataplasm was studied. Extraction of H-179 from dried Andrographis paniculata (Acanthaceae) was optimized. Eight formulation of H-179 cataplasm were tested and compared. One was selected for manufacturing. A preliminary clinical study was then carried out to investigate the clinical effectiveness of H-179 cataplasm for the relief of signs and symptoms associated with arthritis. A group of 80 patients with RA or other arthritis conditions were recruited and were divided into 2 groups, treatment group receiving H-179 cataplasm and control group receiving known transdermal patch from market. The results showed that there was statistically significant improvement in the signs and symptoms and the degree of pain reduction after treatment.

The ultimate goal of this study is to effectively translate the development of a novel herbal transdermal patch into a pragmatic therapeutic product for the treatment of RA. In order to attain this goal, besides the technology itself, there are 2 moderating factors to be considered: one is to comply with the Chinese government on regulatory, safety and environmental issues and the other is to collaborate with local universities with grants to further develop the applied research into a commercial therapy. After consideration of a number of other issues: partner match/relationship, prototype development, product champion, cultural aspects, pioneers users, financial collaboration, strategic alliance, market alliance, time frame, pricing strategy, product compatibility and product strategy, Yunnan Baiyao (YNBY) was selected as collaborator and strategic partner in the commercialization of this H-179 cataplasm in order to ensure the future marketing of this therapeutic though its nationwide network of distribution channels. Along with YNBY, the H-179 cataplasm was patented in China. This study successfully demonstrated the feasibility of a translational research project between the academia and the pharmaceutical industry.
由對免疫系統疾病、癌病、神經退化性疾病、心臟病等疾病的研究轉化為治療該等疾病的方法,生物醫學上的轉化研究拉近了基礎科研與人類切身利益之間的差距,使人類的生活得以改善。於二零零五年,透過嶄新的藥物篩選技術 -- HerboChip®,從中草藥穿心蓮中發現並提取出一種腫瘤壞死因子(TNF-α)的對抗劑 – H-179。筆者期望採用生物醫學的研究轉化取向,實行一系列的研發步驟,使H-179可以商品化,變成種可以治療一種最常見的免疫系統疾病 -- 類風濕關節炎的新方法。為達到此目的,筆者發明新穎的快速商品化概念性框架,並應用在發展出價廉物美的H-179膏藥。根據估計,H-179膏藥推出市場五年後,市場價值大概是人民幣10億元。

基於先前在體外實驗及動物活體實驗的數據顯示,H-179有效地抑制類風濕關節炎的水腫現象,並且在初步的人體臨床試驗中,H-179可有效地舒緩類風濕關節炎的症狀。

本研究論述如何研發一種有效、安全的類風濕關節炎透皮給藥系統 – H-179膏藥。首先,筆者對H-179的生產過程進行優化,包括H-179從穿心蓮的提取、膏藥成份配方等。其次,在初步的人體臨床試驗中觀察H-179膏藥的有效性。此次臨床試驗包括八十位類風濕關節炎的患者,患者被分為兩組,研究組患者接受H-179膏藥,而控制組患者則接受已上市的膏藥。比對兩組的結果後發現,在改善類風濕關節炎的症狀及舒緩痛楚上,H-179膏藥明顯地比較有效。

本研究的最終目的是有效率地轉化科研成果至市場產品,因此有兩大因素必須考慮: 1) 依從中國相關法規、安全及環境等的問題; 2) 與本地大學合作,申請資助進行應用研究及商品開發。結合其他需要列入考慮的因素後,例如伙伴關係、原型開發、文化方面、先導用戶、財務合作、戰略聯盟、市場聯盟、時間表、訂價戰略、產品相容性和產品戰略等,經過篩選後,云南白药被選為策略性合作伙伴,透過其藥物發展的經驗及全國的銷售網絡,可確保H-179膏藥的過程成功。另外,H-179膏藥已在中國申請專利保護。本研究展示一個結合了產、學、研的轉化研究計劃的可行性。