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Herbal drugs/ Pharmaceuticals – Problems and Prognosis Dr. P. Pushpangadan Director, National Botanical Research Institute Lucknow, India 5 trillion $ 2020 62 billion $ 2005 Growing popularity Business standard, 2005 ccessible ffordable ssured safety About 70% Indian population (60-70 crore) depends on alternative system of medicine. WHO Herbal drugs are cheaper than generic drugs !!?? Herbal drugs have been used in India for more than 4000 years. Allopathy or Modern Medicine Glamorized discipline Pursued by most (influenced and so called ‘Literate’) in India and, in western countries Backed by technological advances investigations Based on sound scientific reasoning – experimental evidence; not anecdotal Thus, Modern Medicine is an evidencebased, techno-savvy science that seems to provide ultimate care to sick patients Allopathy or Modern Medicine But???? The treatment is often symptomatic, costly, out of reach of most in developing countries Except for infective pathologies, we do not have much to offer except palliation Treatment of Chronic Lifestyle Disorders like neurodegenerative disorders is often very disappointing and limited by adverse events It treats the Disease (symptomatic) and not the patient ‘as a whole’ (Holistic approach) Therapeutic Objective The ultimate goal of every physician is to “CURE” the disease. Has Allopathy achieved this goal for all ailments? No; Except for infective pathologies, we do not achieve CURE Most often the treatment is Symptomatic and Palliative. Effective & Safe Medicine Drug Discovery – problems It is notoriously inefficient One in a hundred thousand or more compounds will enter the market as a drug Pharma majors have NO interest in higher plants extracts for screening for biological activity In NAPRALERT ethnomedical reports for 14,300 species (5.2% of all plant species) are there; But 58% of these species have never been examined biologically or chemically Of these 74% are used in a manner which parallels their ethnomedical use Golden triangle Traditional medicine Modern medicine Modern science Thus making cheaper affordable and safe medicine Mashelkar 2005 Examples of some important plant derived drugs Compound Plant Species Acetyl digoxin Digitalis lanata Ajmalicine Catharanthus roseus, Rauwolfia sp. Ajmmaline Rauvolfia serpentina Andrographolide Andrographis paniculata Artemissine Artemisia annua Asiaticoside Centella asiatica Berberine Berberis spp. Caffeine Camellia sinensis Caffeine Camellia sinensis Cocaine Erythroxylum cocoa Codeine Papaver spp. Codiene Papaver somniferum Colchicine Colchicum autumnale, Gloriosa superba Curcumin Curcuma longa Digitoxin, Digoxin, Digitoxigenin Digitalis spp. Emetine Cephaelis ipecacuanha Ephedrine Ephedra gerardiana Ergometrine, Ergotamine, Ergotoxin Claviceps purpurea on Rye plants Glycyrrhizin, Glycyrrhizinic acid Glycyrrhiza glabra Hesperidin Citrus spp. Mentha spp. Contd.. Examples of some important plant derived drugs (Contd..) Hyoscine Duboisia spp. Hyoscyamine Datura spp, Hyscyamus spp. L-Dopa Mucuna pruriens Menthol Mentha spp. Morphine Papaver spp. Papain Carica papaya Podophyliotoxin Podophyllum emodi Quinine, Quinidine Cinchona spp. Reserpine & Deserpidine Rauvolfia serpentina, Rutin Eucalyptus spp, Fagopyrum spp, Sophora japonica Scopolamin Datura sp. Sennosides A&B Cassia angustifolia, C. acutifolia Silymarin Silybum marianum Strychnine Strychnos nux-vomica Taxol Taxus baccata Thymol Vinblastine, Vincristine Xanthotoxin Chemical Intermediates Citral Diosgenin Phytosterols (Stigmasterol & Sitosterol) Thymus vulgaris Catharanthus roseus Ammi majus, Heracleum candicans Solasodine Hypercin, Hyperforin Solanum Hypericum perforatum Lemon grass Dioscorea spp. Costus spp. Soya & Calabar Beans Traditional medicine Historical background Earliest recorded use of a medicinal plant has been mentioned in ‘Rigveda’ one mentioned in the modern texts is that of the herb called “Ma huang” a species of Ephedra used medicinally in China for over 5000 years Cinchona was used by local south American tribes long before before the isolation of quinine for treating malaria Source of aspirin (Salix officinalis) was used as pain killer for long time before being identified Traditional medicines Middle of 19th century, 80% of all medicines were herbal Even today 25% of drugs are derived from plant source Most of these drugs came from traditional lead, folk knowledge etc. Some of these still could not substituted despite the enormous advancement in synthetic chemistry eg. Reserpine, taxol, vincristine etc. Revival of herbal medicine widespread belief that ‘green’ medicine is healthier than synthetic products leading to rapid spurt of demand for health products like herbal tea, ginseng and such products of traditional medicine So rapid – sale of herbal products are staggering 100 billion dollars a year. After India and China, even the western world has started working on herbals NIH has set up CAM center and working on St. John’s wort and Gingko biloba Drug development based on traditional leads Survey of traditional remedies Choice of plant Traditional formulation Related species Identification, authentication Collection Extraction Clinical trial Biological screening Effective Active 1. Analytical standard 2. Safety 3. Modernise Technology 4. New Dosage Forms Pharmacokinetics/Pharmacodynamics Pilot Plant Production Bioassay Linked Fractionation Active Compound(s) Characterisation Pure Compound, Standardised Extracts 1. Pharmacology 2. Toxicity 3. Clinical Pharmacology Clinical Trials Bio-availability Registration Commercial Production Marketing Reverse pharmacology What is required is “Scientific evidence” Answer lies in providing scientific validation for efficacy and safety Screening based on ethnomedical and ethnobotanical lead as chances of hitting the target is more System biology The health triangle. The survival potential of all living systems, H, is expressed in the health triangle, structured with life’s common denominator: Intelligence, Energy and Organization. Synergy Most of the effective phytomedicine in market are as whole extracts of plants Practitioners believe that synergistic interactions between the components of individual or mixture of herbs are a vital part of therapeutic efficacy Mechanism of action of many phytomedicine is still unknown and there are several instance where total extract shows better activity than an equalent dose of isolated compound chemical and pharmacological evidence to demonstrate conclusively the concept of synergism Multi-target approach Combinations of herbs are normal and are based on empirical observation and reasoning based on a particular patient these herbal combinations may not be targeted to a particular organ (multi-targeted), cell, tissue or any biochemical system, making this synergy even more difficult to identify possibility of drug interactions and the adverse reactions arising out of these have to be checked before coming out with the drug Multiple Targets Need A Combo Plant A Plant B Plant C Plant D Plant E Plant F Plant G Plant H Pain, Cartilage Inflammation Oxidative stress Osteoporosis Anabolic CNS Immunomodulator Antistress Bioavailability Lubricant Activity Matrix: Systems-Biology Approach Pharmacovigilance Any thing herbal is safe!!????? Adverse drug reactions (ADR) Drug-drug interactions Herb-Drug interactions Toxicity of the isolated ingredients Traditional process (Shodhana) Traditional Medicine: Threats Poor positioning on a global level Ignored by the global scientific community Very little scientific research validations Very little publications in peer-reviewed science Journals Deliberate negative propagandas Traditional medicine: Future Innovative, Effective and Aggressive use of Emerging Technologies without Compromising the Basic Principles will be the main key towards the bright future Final Product Global Market Traditional Approach Selection of potential plants Extraction and fractionation IPR Drug Discovery Activity guided isolation of active copounds Clinical studies Standardization of the formulation(s) Toxicity stuides Formulation and Doasge studies Pharmacological studies