Detailed Project Report (DPR) on colchicine and thiocolchicine

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)