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Exploring Nature’s Medicine Chest

Fri, 10/05/2012 - 4:29pm
Roger Schenck, Content Manager; Chemical Abstracts Service, Columbus, Ohio

Natural products have been used for millennia to treat a variety of diseases. Hippocrates, the father of modern medicine, noted that a powder derived from the bark of the willow tree helped reduce pain from headaches. In the 1800s, chemists isolated this beneficial substance, salicylic acid, and refined it by buffering sodium salicylate with acetyl chloride to create acetylsalicylic acid or aspirin.

More recently, traditional medicine patents have been increasingly recognized as a rich source of natural products for potential drug discovery. Databases from Chemical Abstracts Service (CAS), a division of the American Chemical Society (ACS), have mined this wealth of research by providing access to information disclosed in more than 50,000 traditional medicine patent records from Pacific Rim countries, especially China.

Everything old is new again
Traditional medicine is the knowledge, skills, and practice of maintaining health and treating physical and mental illness based on observations, beliefs, and experiences indigenous to different cultures. In some countries, traditional medicine is the primary means of health care for the majority of the population.

Today, traditional medicines and treatments are often used in alternative or complementary therapies, alone or as adjuncts to modern medical treatments, where they may have fewer side effects. Ginger, for example, is often recommended to safely relieve pregnancy-related nausea.
Traditional medicines may also provide effective alternatives for drug-resistant diseases or may be developed less expensively than new drugs.
Because of their promise, many traditional medicines are being investigated for multiple therapeutic uses. Astragalus, Angelica sinensis, peony, sage, and Ligusticum chuanxiong (Szechuan lovage) are being studied as analgesics, anti-inflammatories, antibacterials, and hypertension medicines.

Botanicals used in traditional medicines are indeed yielding successful drugs. Milk thistle (Silybum marianum), used to treat liver ailments, can be traced back to ancient Greece and Rome. More recently, its active compound, silybin, has been studied as an antitumor agent and is currently in clinical trials. In one randomized clinical trial in children with acute lymphoblastic leukemia, silybin decreased the harmful effects of chemotherapy on the liver without diminishing the effects of cancer treatment.

Traditional medicine successes such as these, as well as the increasing pace of plant species’ extinctions, have also spurred the determined search for novel natural substances possessing therapeutic activities. For example, Taxol (paclitaxel), a well-known chemotherapy drug, was discovered as part of a U.S. Department of Agriculture program to find natural products that might be used as drugs. Discovered in the bark of the rare Pacific yew (Taxus brevifolia) tree, the production of taxol originally threatened that species’ existence. Fortunately, scientists were able to derive the active compound from the abundant European yew using semisynthetic production, which sustained paclitaxel’s availability for chemotherapy, as well as the Pacific yew’s existence.

To progress from “ancient Chinese secret” to modern commercial viability, natural products have been part of the patenting tradition since the 1990s, steadily amassing a significant body of work. For example, Yung-Chi Cheng, a cancer researcher at Yale, has been studying a four-herb combination discovered 1,800 years ago by Chinese herbalists. The herbal combination, dubbed PHY906 by the researchers, is effective at minimizing the side effects of chemotherapy. Patented in 2009 (U.S. Patent 7534455), it is now in Phase 2 clinical trials.

Traditional medicine content in literature
Traditional medicine patents and other relevant published literature constitute a unique form of prior art for intellectual property professionals. Until recently, however, much of the traditional medicine information has been largely inaccessible for a number of reasons, such as unavailability in scientific databases, and the lack of English language translations.  To fill this gap, CAS’ databases include articles from 2,100 Asian journals and all major Asian patent authorities, providing English language abstracts of traditional medicine information from these patents.

Asia is the regional leader in traditional medicine patents, with more than 90% reported. Among these, China represents 60%, Japan 20%, and South Korea 10%. The remaining 10% are reported from a variety of countries, including the United States, France, and Canada.

To aid search and retrieval, CAS experts intellectually assign consistent, controlled terminology from the CAS Lexicon. This lexicon records the vast vocabulary of chemistry and related sciences drawn from more than a century of research. For traditional medicine, terminology includes taxonomic terms, disease terms, and substance class terms, as well as specific substance names.

While the majority of traditional medicine patents are indexed as “Natural products, pharmaceutical,” a review of the CAS Lexicon entry for this term reveals additional related terminology including Ayurvedic drugs, Chinese herbal medicine, and Oriental drugs. Similarly “medicinal plants” provides a list of specific medicinal plants that also can be used to refine or expand a search.

CAS experts correct numbers, stereochemical designations, names, and chemical structures that may be incorrect in original documents. This ensures that searches yield precise results while limiting irrelevant results.

Finding natural product pharmaceuticals
Several approaches can be used to find natural product pharmaceuticals, including searching for a plant or organism name, by common or genus-species name; for medical condition by specific name or affected organ; and for therapeutic indications such as antitumor agents or immunostimulants.

In the case of the Pacific yew, searching the common name (or the genus-species name Taxus brevifolia) within the SciFinder tool yields more than 585 references. SciFinder analysis and refinement tools can focus search results to the specific area of interest. In-depth breakdown of the indexing by organism name, medical terms, or substances can be obtained, as can molecular structures isolated from natural products. Saved answer sets can then be combined. Researchers also can view Substance Detail records for complete names, formula, structure, properties, and related information.

Prognosis
There is little doubt ancient medicinal ingredients will continue to be reported in patent literature for remedies to treat modern ailments. To discover this prior art, intellectual property professionals in the life sciences can turn to the CAS databases for natural product information. This information can lead to subsequent developments in isolating active ingredients from natural products or creating synthetic pathways to important pharmaceuticals.

About the author
Roger Schenck is the manager of CAS’ content planning department, working with its customers to ensure CAS is building the right databases for the future.

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