HEALTH HERITAGE

1. HEALTH HERITAGE SANGAM* OF ANCIENT WISDOM AND MODERN SCIENCE R.R. Hirwani Head CSIR Unit for Research and Development of Information Products, Pune, India GRA MEETING 1 February 2006 *SANGAM ~ CONFLUENCE

2. ORGANISATION OF PRESENTATION • BACKGROUND • OBJECTIVES • FEATURES • CONTENTS • DEMONSTRATION • BRIDGE BETWEEN TK AND MODERN SCIENCE • IPR ISSUES • CURRENT TRENDS • INTO THE FUTURE

3. BACKGROUND • AYURVEDA – INDIAN SYSTEM OF MEDICINE • KNOWLEDGE CODIFIED IN SANSKRIT SINCE 12TH CENTURY B.C.- SCRIPTURES AVAILABLE IN PUBLIC DOMAIN • INSTITUTIONALISED EDUCATION, RESEARCH AND PRACTICE • MEDICINAL PLANTS - PRIMARY SOURCE OF MEDICINE • EXTENSIVE RESEARCH ON NATURAL PRODUCTS AND PLANT CHEMISTRY • ISOLATION AND CHARACTERISATION OF CHEMICAL CONSTITUENTS • STUDY OF STRUCTURE - ACTIVITY RELATIONSHIPS • KNOWLEDGE USEFUL FOR LIFE SCIENCE INDUSTRY

4. OBJECTIVES • PUT TRADITIONAL KNOWLEDGE IN PUBLIC DOMAIN IN ENGLISH LANGUAGE IN MODERN ELECTRONIC FORMAT • LINK TRADITIONAL KNOWLEDGE TO MODERN SCIENTIFIC AND PATENT LITERATURE • USE DATABASE FOR DEFENSIVE AND POSITIVE LEGAL PROTECTION • ADDRESS ‘PATENTABILITY’ ISSUES • INCREASE INTERNATIONAL RECOGNITION OF TRADITIONAL KNOWLEDGE SYSTEMS • CATALYSE SCIENTIFIC COLLABORATION

5. FEATURES OF HEALTH HERITAGE DATABASE • NON-PATENT AND PATENT LITERATURE ON MEDICINAL PLANTS WIDELY USED IN AYURVEDA • REPRODUCTION OF TRADITIONAL KNOWLEDGE (ORIGINAL SANSKRIT, TRANSLITERATION AND TRANSLATION) • SUMMARY OF CHEMICAL, BIOLOGICAL AND MEDICINAL/CLINICAL STUDIES DONE ON MEDICINAL PLANTS AND THEIR EXTRACTS • STRUCTURES OF NEW CHEMICALS ISOLATED • FULL TEXT OF PATENTS • BIBLIOGRAPHIC REFERENCES • FREE TEXT SEARCH FACILITY • DEMO OF HEALTH HERITAGE /WIPO PORTAL

6. AYUTA INDEX • KNOWLEDGE OF AURVEDA CAN BE CLASSIFIED IN THREE BASIC PARTS • HETU (CAUSE) • LAKSHAN (SIGNS AND SYMPTOMS) • AUSHADH (TREATMENT) • INFORMATION SCATTERED IN DIFFERENT TEXTS • COMPILED REFERENCES FROM FOUR PRINCIPLE TEXTS IN AN INDEXED FORM • BROUGHT TOGETHER ALL THE EFFECTS RESULTING FROM EVERY SIGNLE CAUSE, ALL ETIOLOGICAL FACTORS WHICH CAN CAUSE EVERY SINGLE DISEASE OR CONDITION AND TREATMENT METHODS • PREPARATION OF COMPUTER READABLE DATABASE MADE DATA MINING EASY-DIAGNOSTIC SOFTWARE

7. Vol. 215 8.1.1982 IS THE ACETYLCHOLINE RECEPTOR A RABIES VIRUS RECEPTOR ? BRIDGE BETWEEN TK AND MODERN SCIENCE ABSTRACT Rabies virus was found on mouse diaphragms and on cultured chick myotubes in a distribution coinciding with that of the acetylcholine receptor. Treatment of the myotubes with -bungarotoxin and d-tubocurarine before the addition of the virus reduced the number of myotubes that became infected with rabies virus. These findings together suggest that acetylcholine receptors may serve as receptors for rabies virus. The binding of virus to acetylcholine receptors, which are present in high density at the neuromuscular junction, would provide a mechanism whereby the virus could be locally concentrated at sites in proximity to peripheral nerves facilitating subsequent uptake and transfer to the central nervous system. Lentz et. al.

8. BRIDGE BETWEEN TK AND MODERN SCIENCE Datura as a prophylaxis for rabies The affected person be made to drink the essence of Arka tree. This will clear his stomach of poison, if any, by vomiting. Sveta, Punarnava or Datura be administered. Palala, Oilseeds of Tila and essence of Rupika with Joggery drain the poison of Alarka (mad dog) as the wind drives away the clouds.

9. Karsa measure of root of Sarapunkha along with a half of Datura measure be mixed with the rice-water be ground with wet rice - this paste be wrapped by Unmattaka leaves and cooked as a cake. • This cake be eaten by a person, who is bitten by Alarka and poisoned. Whatever the ills caused by the bite of mad dog are cured by this medicine.

10. DATURA AS A PROPHYLAXIS FOR RABIES • CHEMICAL CONSTITUENTS OF DATURA ARE SCOPOLAMINE, ATROPINE AND MANY OTHER ALKALOIDS • THESE ALKALOIDS PREDOMINANTLY BLOCK THE MUSCARNIE ACTION OF ACETYLCHLORINE • DATURA FOR RABIES TREATMENT REPRESENTS THE FIRST DOCUMENTED EXAMPLE OF PROPHYLAXIS BY RECEPTOR BLOCKADE

11. THERAPEUTICS FOR CEREBRAL MALARIA Active Principle of Chinese Plant Artemisia annua Known Since 340 AD

12. PATENTS FOR ANTIMALARIAL COMPOSITIONS United States Patent 5,219,865 Chatterjee ,   et al. (Hoechst) June 15, 1993 Pharmaceutical combination for the prophylaxis and therapy of malaria Abstract The present invention relates to combinations of the malaria therapeutics artemisinine,dihydroartemisinine, arteether, artemether,artesunate or other artemisinine derivatives with one or more of the antimalarials chloroquine, 10-0-methylfloxacrine, quinine, mefloquine, amodiaquine, pyrimethamine, sulfadoxine and primaquine. Synergistic actions are achieved with them on treatment of mammals, including humans, with subcurative doses of the individual substances. United States Patent 5,677,331 Zhou ,   et al. (Ciba Geigy) October 14, 1997 Antimalarial compositions Abstract The invention relates to a synergistic antimalarial composition which comprises the antimalarial agent benflumetol and also an antimalarial agent from the artemisinine group such as artemether. The composition can be formulated into solid dosage forms such as tablets and is useful for the treatment of drug resistant malaria.

13. IPR ISSUES • IP PROTECTION BEYOND TK ON MEDICINAL PLANTS • ACTIVE INGREDIENTS / CHEMICAL CONSTITUENTS • COMBINATION OF CONSTITUENTS OF NATURAL PRODUCTS AND SYNTHETIC COMPOUNDS • MINOR VARIANTS OF NATURALLY OCCURRING COMPOUNDS • EMPHASIS ON ‘PATENTABILITY’ AND ‘VALIDITY’

14. PATENT ON AROMATIC,MEDICINAL AND ECONOMIC PLANTS(PAMEP) • PROJECT SUPPORTED BY DBT • STUDY PATENTS ON 2000+ PLANTS • EMPHASIS ON TECHNOLOGIES AND APPLICATIONS • INPUT FOR CONSERVATION AND DEVELOPMENT OF BIODIVERSITY

15. PAMEP . • Plant Breeding, Propagation and Cultivation • Formulations and their methods of preparation • Food Applications • Industrial Uses • Active Components • Agrochemical uses • Dietary Supplements • Processing • Traditional Usage • New Medicinal Usage • Harvesting and post-harvest processing • Other Misc. Uses

16. PATENT MAPPING FOR RESEARCH PLANNING

17. CURRENT TRENDS • VALIDATION OF AYURVEDA CONCEPTS ON MODERN SCIENTIFIC PRINCIPLES • CREATE VALUE BY SYNTHESIS BETWEEN ANCIENT INSIGHTS AND MODERN DISCOVERIES • INNOVATION BY SCIENTIFICATION OF TRADITIONAL MEDICINAL KNOWLEDGE

18. VALIDATION OF AYURVEDA CONCEPTS • CLASSIFICATION OF MEDICINAL PLANTS BASED ON MECHANISM OF ACTION • CASE STUDIES -THERAPEUTICS : DIABETES - COSMECEUTICALS : SKIN CARE

19. MECHANISMS FOR DIABETES • BETA CELL ACTIVATION • BETA CELL REGENERATION • PANCREATIC TONING/ PROTECTION • INSULIN MIMICKING • IMPROVEMENT OF GLUCOSE TOLERANCE/ INSULIN EFFICIENCY • REDUCTION OF GLUCOSE ABSORPTION • IMPROVEMENT IN CARBOHYDRATE METABOLISM • IMPROVEMENT OF FAT METABOLISM • OTHER MECHANISM

20. COSMECEUTICALS – SKIN CARE • HYPER-PIGMENTATION/SKIN LIGHTENING • ANTI-AGING • WOUND HEALING • ACNE • SUN PROTECTION • SKIN INFECTIONS

21. MECHANISM FOR HYPER-PIGMENTATION/SKIN LIGHTENING • TYROSINASE INHIBITION • MELANOGENESIS INHIBITION • SUPPRESSING ENDOTHELIN- 1 FORMATION • REDUCTION OF KERATINOCYTE DERIVED IMMUNOSUPPRESSIVE CYTOKINES • PREVENT UVB-INDUCED IMMUNE SUPPRESSION IN THE SKIN • PIGMENTATION INHIBITORY EFFECT

22. MINERALIA MEDICA • MEDICINES OF MINERAL ORIGIN WERE WIDELY USED • BHASMAS ARE STILL IN USE • HAS REMAINED AS NEGLETED AREA OF RESEARCH DUE TO PERCEPTION OF TOXICITY • NO MENTION OF BHASMAS IN THE CHEMICAL ABSTRACTS FROM VOL.1 (1906) TO TILL DATE • ON INTERNET ONLY COMMERCIAL INFORMATION AVAILABLE • NO CLASSICAL WORK TRANSLATED IN ENGLISH LANGUAGE • COMPILED ALL THE LITERATURE ON BHASMAS, TRANSLATED IN ENGLISH,COLLECTED SCIENTIFIC LITERATURE • PCT APPLICATION ON ONE PARTICULAR BHASMA ALREADY BEEN FILED

23. METALLOPHARMACEUTICALS • METAL BASED DRUGS - CANCER (Pt) • ANTI-INFLAMMATORY DRUGS - Cu OR Zn • ANTIDIABETIC DRUG -Cr AND V • ANTIMICROBIALS - Zn, Bi, METAL CLUSTERS • DEGENERATIVE DISEASES - Cu, Zn AND Fe • EMERGING TECHNOLOGIES - NANOTECHNOLOGY

24. LEECH

25. LEECH • LEECHES HAVE BEEN USED AS AN ALTERNATIVE TREATMENT TO BLOOD LETTING AND AMPUTATION FOR SEVERAL THOUSAND YEARS • IT WAS USED FIRST FOR MEDICINE IN ANCIENT INDIA ABOUT 1000 BC • IN AYURVEDA LEECH THERAPY IS CALLED AS JALOUKA PRAYOGA • LEECH SALIVA HAS ANALGESTIC AND ANASTHETIC EFFECT •  MAJOR SPECIES USED IN MEDICINE Ø      HIRUDO MEDICINALIS - EUROPEAN Ø      HIRUDINARIA MANILLENSIS - ASIAN Ø      HAEMENTERIA GHILIANII - AMAZON

26. US FDA APPROVAL • IN JUNE 2004, US FOOD AND DRUG ADMINISTRATION CLEARED THE FIRST APPLICATION FOR LEECHES TO BE USED FOR COMMERCIAL MARKETING IN MODERN MEDICINE AS MEDICAL DEVICES •  RICARIMPEX SAS , A FRENCH FIRM, WAS THE FIRST COMPANY TO REQUEST AND RECEIVE FDA CLEARANCE TO MARKET LEECHES AS MEDICAL DEVICE •  FDA DETERMINED THAT LEECHES ARE MEDICAL DEVICES BECAUSE THEY MEET THE DEFINATION OF A MEDICAL DEVICE UNDER THE FOOD, DRUG AND COSMETICS ACT

27. LEECH THERAPY • SKIN GRAFTING AND REATTACHMENT SURGERY • APPLICATION ON ARTHRITIC KEEN REDUCES JOINT PAIN AND SWELLING • PLASTIC AND RECONSTRUCTIVE SURGERY – PROVIDES CRITICAL VENOUS OUTFLOW FOR TISSUE REPLANTATION • BREAST RECONSTRUCTION • REDUCES POST SURGERICAL VENOUS ENGORGEMENT • CONTINUOUS VENOVENOUS HEMODIALYSIS IN LIVER TRANSPLANTATION • LEECHES APPLIED ON THE TIP OF THE TONGUE TO REMOVE THE SYMPTOMS CHARACTERISTIC FOR GLOSSALGIA

28. HIRUDIN • HIRUDIN-NATURALLY OCCURRING PEPTIDE IN THE SALIVARY GLANDS OF LEECHES • ANTICOAGULANT • INHIBIT THE THROMBIN CATALYTIC SITE • DOES NOT INTERFERE WITH OTHER SERUM PROTEINS AND CAN ACT ALSO ON BOUND THROMBIN • RELIEVES ACUTE VENOUS CONGESTION • REDUCES THE RISK OF NONFATAL MYOCARDIAL INFARCTION IN ACUTE CORONARY SYNDROME

29. MODERN RESEARCH • INHIBITOR HUMAN TRYPTASE ISOLATED FROM LEECHES • BIVALIRUDIN (HIRULOG) INHIBITS THROMBOSIS • HIRULLIN POLYPEPTIDE A STRONG ANTITHROMBIC ACTIVITY • ANTIMETASTATIC FACTOR COMPRISING A PROTEIN SUBSTANCE HAVING FACTOR XA INHIBITORY ACTIVITY ISOLATED FROM SALIVARY GLAND OF HAEMENTERIA GHILIANII • HEMENTIN, A POLYPEPTIDE DERIVED FROM LEECH SALIVARY GLANDS FOR PREVENTS FORMATION AND DEAGGREGATION OF PLATELET-RICH CLOTS OR THROMBUS • HIRUDIN (OR RELATED CHEMICALS) HAVE BEEN SYNTHESISED USING RECOMBINANT-DNA TECHNOLOGY.

30. CONTD.. MODERN RESEARCH • A RECOMBINANT ANTISTASIN TYPE SERINE PROTEINASE INHIBITORS •  POLYPEPTIDE INHIBITING C1 ESTERASE AND /OR FACTOR XII USED IN GENE THERAPY FOR CARDIOVASCULAR, INFLAMMATORY OR AUTO IMMUME DISORDES • PROTEIN BLOCKS STIMULATION OF PLATELET AGGREGATION BY COLLAGEN USEFUL IN TREATMENT OF THROMBOTIC DISEASES • NEW THROMBOLYTIC ENZYME DESTABILASE, ENDO-EPSI(GAMMA-GLU)-LYS-ISOPEPTIDASE, SHOWING EXO-EPSI(GAMMA-GLU)-LYS-ISOPEPTIDASE AND AMIDOLYTIC ACTIVITY OBTAINED FROM HIRUDINIDAE • RECOMBINANT PROTEIN HAVING FIBRINOLYTIC AND COAGULATION-FACTOR XA-INHIBITING AMINO ACID SEQUENCE-INHIBITING PROPERTIES

31. INTO THE FUTURE • LINK BETWEEN PHARMACOGENOMICS AND TMK • PERSONALISED MEDICINE • CONVERT CONCEPTS INTO PRODUCTS,DEVICES,MACHINE • KNOWLEDGE and IPR MANAGEMENT IS THE KEY

32. IN CONCLUSION IT MIGHT WELL BE SAID OF ME THAT HERE I HAVE MERELY MADE UP A BUNCH OF OTHER MEN’S FLOWERS, AND PROVIDED NOTHING OF MY OWN BUT THE STRING TO BIND THEM. - MONTAIGNE, ESSAIS

33. CSIR Unit for Research and Development of Information Products85/1 Paud Road, Pune - 411038

34. MECHANISMS FOR ANTI-STRESS • ACETYLCHOLINE RELEASE • ANTI-FATIGUE EFFECT • ADAPTOGENIC ACTIVITY • ANTIDEPRESSANT ACTIVITY • CATECHOLAMINE SECRETION • ANTIOXIDANT ACTIVITY • ANXIOLYTIC EFFECT • AS IMMUNO-ENHANCER

35. MECHANISMS FOR OBESITY • ALPHA AMYLASE INHIBITORS/STARCH BLOCKERS • LIPASE INHIBITORS • INHIBITS LIPID DROPLET ACCUMULATION IN FAT CELLS • WEIGHT CONTROL / ENHANCING WEIGHT LOSS • REDUCING BODY MASS INDEX • AFFECTING BILE ACID ABSORPTION • HYPOLIPIDEMIC- LOWERING CHOLESTEROL CONTENT OF LOW-DENSITY LIPOPROTEIN (LDL) • ELEVATING HIGH-DENSITY LIPOPROTEIN (HDL) CHOLESTEROL CONCENTRATIONS • SERUM CHOLESTEROL AND TRIGLYCERIDE LEVELS REDUCTION • APPETITE SUPPRESSANT

36. MINERALIA MEDICA • MEDICINES OF MINERAL ORIGIN WERE WIDELY USED • BHASMAS ARE STILL IN USE • HAS REMAINED AS NEGLETED AREA OF RESEARCH DUE TO PERCEPTION OF TOXICITY • NO MENTION OF BHASMAS IN THE CHEMICAL ABSTRACTS FROM VOL.1 (1906) TO TILL DATE • ON INTERNET ONLY COMMERCIAL INFORMATION AVAILABLE • NO CLASSICAL WORK TRANSLATED IN ENGLISH LANGUAGE • COMPILED ALL THE LITERATURE ON BHASMAS, TRANSLATED IN ENGLISH,COLLECTED SCIENTIFIC LITERATURE • PCT APPLICATION ON ONE PARTICULAR BHASMA ALREADY BEEN FILED

37. AYUTA INDEX • KNOWLEDGE OF AURVEDA CAN BE CLASSIFIED IN THREE BASIC PARTS • HETU (CAUSE) • LAKSHAN (SIGNS AND SYMPTOMS) • AUSHADH (TREATMENT) • INFORMATION SCATTERED IN DIFFERENT TEXTS • COMPILED REFERENCES FROM FOUR PRINCIPLE TEXTS IN AN INDEXED FORM • BROUGHT TOGETHER ALL THE EFFECTS RESULTING FROM EVERY SIGNLE CAUSE, ALL ETIOLOGICAL FACTORS WHICH CAN CAUSE EVERY SINGLE DISEASE OR CONDITION AND TREATMENT METHODS • PREPARATION OF COMPUTER READABLE DATABASE MADE DATA MINING EASY-DIAGNOSTIC SOFTWARE