COLCHICINE AND THIOCOLCHICINE [3641]
Colchicine is a medication most commonly used to treat gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum (autumn crocus, Colchicum autumnale, also known as "meadow saffron"). Adverse effects are primarily gastrointestinal upset at high doses. In addition to gout, colchicine is used to treat familial Mediterranean fever, pericarditis, and Behçet's disease. The plant source of colchicine, the autumn crocus (Colchicum autumnale), was described for treatment of rheumatism and swelling in the Ebers Papyrus (ca. 1500 B.C.), an Egyptian medical papyrus. Colchicum extract was first described as a treatment for gout in De Materia Medica by Pedanius Dioscorides, in the first century AD. Use of the bulb-like corms of Colchicum to treat gout probably dates to ca. 550 AD, as the "hermodactyl" recommended by Alexander of Tralles. Colchicum corms were used by the Persian physician Avicenna,were recommended by Ambroise Pare in the sixteenth century, and appeared in the London Pharmacopoeia of 1618. Colchicum plants were brought to America by Benjamin Franklin, who suffered from gout himself and had written humorous doggerel about the disease during his stint as envoy to France. Colchicine was first isolated in 1820 by the French chemists P.S. Pelletier and J.B.Caventou. In 1833, P.L. Geiger purified an active ingredient, which he named colchicine. The determination of colchicine's structure required decades, although in 1945 Michael Dewar made an important contribution when he suggested that, among the molecule's three rings, two were 7-member rings. Its pain-relieving and anti-inflammatory effects for gout were linked to its ability to bind with tubulin. Oral colchicine had been used for many years as an unapproved drug with no prescribing information, dosage recommendations, or drug interaction warnings approved by the U.S. Food and Drug Administration (FDA). On July 30, 2009 the FDA approved colchicine as a monotherapy for the treatment of three different indications (familial Mediterranean fever, acute gout flares, and for the prophylaxis of gout flares, and gave URL Pharma a three-year marketing exclusivity agreement in exchange for URL Pharma doing 17 new studies and investing $100 million into the product, of which $45 million went to the FDA for the application fee. URL Pharma raised the price from $0.09 per tablet to $4.85, and the FDA removed the older unapproved colchicine from the market in October 2010 both in oral and IV form, but gave pharmacies the opportunity to buy up the older unapproved colchicine. Colchicine in combination with probenecid has been FDA approved prior to 1982. In August 2009, colchicine won Food and Drug Administration (FDA) approval in the United States as a stand-alone drug for the treatment of acute flares of gout and familial Mediterranean fever. It had previously been approved as an ingredient in an FDA-approved combination product for gout. The approval was based on a study in which two doses an hour apart were effective at combating the condition.
COST ESTIMATION
Plant Capacity 6 Kg/Day
Land & Building (1.5 Acre) Rs. 3.39 Cr
Plant & Machinery Rs. 1.75 Cr
Working Capital for 1 Month Rs. 3.76 Cr
Total Capital Investment Rs. 9.42 Cr
Rate of Return 36%
Break Even Point 42%
INTRODUCTION
FDA APPROVAL
SOURCES OF COLCHICINE
SOURCES OF COLCHICINE
COLCHICUM AUTUMNALE
COLCHICUM LUTEUM
IPHEGENIA INDICA
GLORIOSA SUPERBA
PROPERTIES OF THIOCOLCHICINE
THIOCOLCHICINE
PROPERTIES & FUNCTION OF COLCHICINE
FORMULA C22H25NO6
CAS NAME COLCHICINE
FUNCTION OF COLCHICINE
EXPLANATION
COMPOSITION, CLASSIFICATION AND LABELLING OF THIOCOLCHICINE
PHYSICAL HAZARDS
HEALTH HAZARDS
REPRODUCTIVE TOXICITY
GERM CELL MUTAGENCICITY
CARCINOGENCITY
SPECIFIC TARGET ORGAN TOXICITY-SINGLE
SPECIFIC TARGET ORGAN TOXICITY-REPEATED
SPECIFIC CONCENTRATION LIMITS
ENVIRONMENTAL HAZARDS
LABELLING
HAZARD PICTOGRAM
HAZARD STATEMENT
PRECAUTIONARY STATEMENTS
ADDITIONAL TEXT
ADDITIONAL TEXT
LABELLING
RISK PHRASES
SAFETY PHRASES
USES AND APPLICATION OF THIOCOLCHICINE
PHARMACEUTICAL INTERMEDIATE
USES AND APPLICATION OF COLCHICINE
MEDICAL USES
GOUT
OTHER
CONTRAINDICATIONS
ADVERSE EFFECTS
TOXICITY
MECHANISM OF ACTION
CHEMICAL STRUCTURE OF COLCHINOIDS
MARKET SURVEY
EXPORT DATA OF COLCHICINE
IMPORT DATA OF COLCHICINE
OVERVIEW OF PHYTOCHEMICALS
ON THE BASIS OF FORM, MARKET IS SEGMENTED INTO
ON THE BASIS OF FUNCTIONALITY, MARKET IS SEGMENTED INTO
ON THE BASIS OF APPLICATION, MARKET IS SEGMENTED INTO
SOME OF THE KEY PLAYERS IDENTIFIED IN THE GLOBAL PHYTOCHEMICALS
MARKET INCLUDE
BASED ON THE APPLICATION, THE PHYTOCHEMICAL API MARKET IS SEGMENTED
INTO THE FOLLOWING
PRESENT MANUFACTURERS/SUPPLIERS OF COLCHICINE & THIOCOLCHICINE
PHARMACOLOGICAL USE OF COLCHINOIDS
DRUGS WITH COLCHICINE
DRUGS WITH COLCHICINE DERIVATIVES
OCCURANCE AND PROPAGATION OF G SUPERBA
BOTANICAL DESCRIPTION
PROPAGATION
MEDICINAL APPLICATION
AND ETHANOPHARMACOLOGY OF G. SUPERBA
ETHANOPHARMACOLOGY
MANUFACTURING PROCESS
OF COLCHICINE AND THIOCALCHICINE
PROCESS FLOW DIAGRAM OF COLCHICINE EXTRACTION
MANUFACTURE OF THIOCOLCHICINE
PROCESS FLOW DIAGRAM FOR THE MANUFACTURE OF THIOCOLCHICINE
METHOD OF EXTRACTION AND ISOLATION OF ALKALOIDS
ALL THESE FIVE STEPS SHALL BE DISCUSSED INDIVIDUALLY AS UNDER
SAMPLE PREPARATION
LIBERATION OF FREE ALKALOIDAL BASE
EXTRACTION OF ALKALOIDAL BASE
PURIFICATION OF ALKALOIDAL EXTRACT
FRACTIONATION OF CRUDE ALKALOIDS
QUANTIFICATION OF COLCHICINE IN VARIOUS PARTS OF GLORIOSA SUPERBA
BY HPLC
MATERIALS AND METHODS
EXTRACTION PROTOCOLS
TABLE PEAK AREA OBTAINED FOR COLCHICINE EXTRACTED FROM DIFFERENT
PLANT PARTS OF GLORIOSASUPERBAUSING DIFFERENT METHODS
CONCENTRATION COMPARISON
CONCLUSION
ESTIMATION OF COLCHICINE IN TUBERS OF GLORIOSA SUPERBA L
MATERIALS AND METHODS
TABLE COLCHICINE CONTENT IN WILD AND CULTIVATED TUBERS OF GLORIOSA
SUPERBA FROM DIFFERENT AGRO CLIMATIC ZONES OF ODISHA.
FIGURE- COLCHICINE CONTENT IN WILD AND CULTIVATED TUBERS OF
GLORIOSA SUPERBA FROM DIFFERENT AGRO CLIMATIC ZONES OF ODISHA.
FIGURE - TLC PLATES SHOWING COLCHICINE BANDS OF STANDARD
AND TEST SAMPLES
FIGURE- TUBERS OF GLORIOSA SUPERBA FROM DIFFERENT
AGROCLIMATIC ZONES
FIGURE- HPLC CHROMATOGRAM OF STANDARD COLCHICINE. COLCHICINE PEAK
AT THE RETENTION TIME 1.2 MIN DETECTED AT A WAVELENGTH OF 350 NM.
FIGURE.. HPLC CHROMATOGRAM OF COLCHICINE IN CULTIVATED TUBERS
OF ‘NORTH CENTRAL PLATEAU’ MAYURBHANJ (NCP-M).
FIGURE-HPLC CHROMATOGRAM OF COLCHICINE IN CULTIVATED TUBERS
OF ‘NORTH CENTRAL PLATEAU’ KEONJHAR (NCP-K).
FIGURE-HPLC CHROMATOGRAM OF COLCHICINE IN CULTIVATED TUBERS
OF ‘EAST SOUTH EASTERN COASTAL PLAIN(GANJAM)( ESECP-G)
FIGURE- HPLC CHROMATOGRAM OF COLCHICINE IN CULTIVATED TUBERS
OF ‘WESTERN CENTRAL TABLE LAND, BARGARH ( WCTL-B).
COLCHICINE DERIVATIVES AND THEIR PROCESSES
BIOACTIVITY OF COLCHICINE AND ITS DERIVATIVES
MATERIAL SAFETY DATA SHEET OF COLCHICINE
COMPOSITION, INFORMATION ON INGREDIENTS
HAZARDS IDENTIFICATION
FIRST AID MEASURES
FIRE FIGHTING MEASURES
ACCIDENTAL RELEASE MEASURES
HANDLING AND STORAGE
EXPOSURE CONTROLS, PERSONAL PROTECTION
PHYSICAL AND CHEMICAL PROPERTIES
STABILITY AND REACTIVITY
SUPPLIERS OF RAW MATERIALS
GLORIOSA SUPERBA HERB
P TOLUENE SULFONIC ACID
OTHER RAW MATERIALS
SUPPLIERS OF PLANT AND MACHINERY
PULVERIZERS
FILTER PRESS
EVAPORATORS
VACUUM DRYER
CRYSTALLIZER
CENTRIFUGE
BOILERS (BABY)
LABORATORY TESTING EQUIPMENT
PLANT LAYOUT
APPENDIX – A:
01. PLANT ECONOMICS
02. LAND & BUILDING
03. PLANT AND MACHINERY
04. OTHER FIXED ASSESTS
05. FIXED CAPITAL
06. RAW MATERIAL
07. SALARY AND WAGES
08. UTILITIES AND OVERHEADS
09. TOTAL WORKING CAPITAL
10. TOTAL CAPITAL INVESTMENT
11. COST OF PRODUCTION
12. TURN OVER/ANNUM
13. BREAK EVEN POINT
14. RESOURCES FOR FINANCE
15. INSTALMENT PAYABLE IN 5 YEARS
16. DEPRECIATION CHART FOR 5 YEARS
17. PROFIT ANALYSIS FOR 5 YEARS
18. PROJECTED BALANCE SHEET FOR (5 YEARS)
