3D Mol Similar

Colchicine

: Iupac Name：N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide; CAS No.: 64-86-8; Molecular Weight：399.437; Modify Date.: 2022-11-29 07:52; Introduction: Colchicine is a pale-yellow powder that is obtained from various species of Colchicum, primarily Colchicumautumnale L. Its total chemical synthesis has been achieved, but the primary source of colchicine currently remains alcoholextraction of the alkaloid from the corm and seed of C. autumnale L. It darkens on exposure to light and possesses View more+

Request For Quotation

1. Names and Identifiers

: 1.1 Name; Colchicine; 1.2 Synonyms; (-)-N-[(7S,12a5)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]-acetamide (1E)-N-[(7S)-1,2,3,10-Tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]ethanimidic acid (S)-colchicine (S)-N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl) acetamide (S)-N-(5,6,7,9-TETRAHYDRO-1,2,3,10-TETRAMETHOXY-9-OXOBENZO[A]HEPTALEN-7-YL)ACETAMIDE [3H]-Colchicine Acetamide, N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-yl)-, (S)- Acetamide, N-[(7S)-5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]- Colchicin Colchicina Colchicine 64-86-8 Colchicine Acetamide 64-86-8 colchicinum Colchineos Colchisol Colcin Colsaloid Condylon EINECS 200-598-5 Ethanimidic acid, N-[(7S)-5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]-, (1E)- len-7-yl)- MFCD00078484 N-((S)-1,2,3,10-TETRAMETHOXY-9-OXO-5,6,7,9-TETRAHYDRO-BENZO[A]HEPTALEN-7-YL)-ACETAMIDE N-(1,2,3,10-Tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl)acetamide n-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-acetamid n-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl)-acetamide N-[(7S)-1,2,3,10-Tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide; View all

1.3 CAS No.: 64-86-8

1.4 CID: 6167

1.5 EINECS(EC#): 200-598-5

1.6 Molecular Formula: C22H25NO6 (isomer)

1.7 Inchi: InChI=1S/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1

1.8 InChIkey: IAKHMKGGTNLKSZ-INIZCTEOSA-N

1.9 Canonical Smiles: CC(=O)NC1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)OC)OC)OC)OC

1.10 Isomers Smiles: CC(=O)N[C@H]1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)OC)OC)OC)OC

2. Properties

2.1 Density: 1.32

2.1 Melting point: 150-160℃

2.1 Boiling point: RELATIVE DENSITY

2.1 Refractive index: 1.584

2.1 Flash Point: 392.9°C

2.1 Precise Quality: 399.16800

2.1 PSA: 83.09000

2.1 logP: 3.26250

2.1 Solubility: H2O: 10?mg/mL

2.2 Appearance: Colchicine appears as odorless or nearly odorless pale yellow needles or powder that darkens on exposure to light. Used to treat gouty arthritis, pseudogout, sarcoidal arthritis and calcific tendinitis. (EPA, 1998)

2.3 Storage: Light Sensitive.

2.4 Color/Form: white to yellow with a green cast

2.5 Decomposition: When heated to decomposition, colchicine emits toxic fumes of carbon monoxide, carbon dioxide, and nitrogen oxides.

2.6 Odor: Odorless or nearly so

2.7 PH: pH of 0.5% solution: 5.9

2.8 pKa: 12.36(at 20℃)

2.9 Water Solubility: H2O: 45 g/L (20 oC)

2.10 Spectral Properties: Specific optical rotation: -429 at 17 deg C/D (water, 1.72%); -121 deg at 17 deg c/d (concentration by volume = 0.9 g in 100 ml chloroform); max absorption (95% ethanol): 350.5 nm (log epsilon = 4.22), 243 nm (log epsilon = 4.47)
IR: 17152 (Sadtler Research Laboratories Prism Collection)
UV: 5410 (Sadtler Research Laboratories Spectral Collection)
MASS: 35758 (NIST/EPA/MSDC Mass Spectral Database, 1990 Version)

2.11 Stability: Stable. Light sensitive. Incompatible with strong oxidizing agents.

2.12 StorageTemp: 2-8°C

3. Use and Manufacturing

3.1 Definition: An alkaloid plant hormone.

3.2 General Description: Odorless or nearly odorless pale yellow needles or powder that darkens on exposure to light. Used to treat gouty arthritis, pseudogout, sarcoidal arthritis and calcific tendinitis.

3.3 Potential Exposure: Colchicine is a drug used to treat gouty arthritis, pseudogout, sarcoidal arthritis; and calcific tendonitis.

3.4 Shipping: UN1544 Alkaloids, solid, n.o.s. or Alkaloid salts, solid, n.o.s. poisonous, Hazard Class: 6.1; Labels: 6.1- Poisonous materials, Technical Name Required. UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials

3.5 Usage: It can be used for the study of plant genetics; used as selenium reagent; clinically as anticancer drugs. The product is a typical mitosis toxin. It can be used for treating acute gout and breast cancer. It can also be used as selenium reagent, for being applied to plant genetics and cancer research. It is a kind of antineoplastic agents and anti-gout for being used for the treatment acute gout and for the treatment of tumors

4. Safety and Handling

4.1 Symbol: GHS05, GHS06, GHS08

4.1 Hazard Codes: T+

4.1 Signal Word: Danger

4.1 Risk Statements: R26/28

4.1 Safety Statements: S13;S45

4.1 Exposure Standards and Regulations: The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl colchicine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

4.2 Packing Group: I

4.2 Octanol/Water Partition Coefficient: log Kow = 1.03

4.3 Fire Hazard: Stable.

4.4 Other Preventative Measures: SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

4.5 Hazard Class: 6.1

4.5 Hazard Declaration: H300 + H330-H318-H340

4.5 Cleanup Methods: Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labelled container for disposal. Wash spill site.
Do not touch or walk through the spilled agent if at all possible. However, if you must, personnel should wear the appropriate personal protective equipment (PPE) during environmental decontamination. ... Keep combustibles (e.g., wood, paper, and oil) away from the spilled agent. Use water spray to reduce vapors or divert vapor cloud drift. Avoid allowing water runoff to contact the spilled agent. Do not direct water at the spill or the source of the leak. Stop the leak if it is possible to do so without risk to personnel, and turn leaking containers so that gas rather than liquid escapes. Prevent entry into waterways, sewers, basements, or confined areas. Isolate the area until gas has dispersed. Ventilate the area.

4.6 DisposalMethods: SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

4.7 RIDADR: UN 1544

4.7 Fire Fighting Procedures: If a tank, rail car, or tank truck is involved in a fire, isolate it for 0.5 miles (800 m) in all directions; also consider initial evacuation for 0.5 miles (800 m) in all directions.
For large fires, use water spray, fog, or regular foam. Move containers from the fire area if it is possible to do so without risk to personnel. Dike fire control water for later disposal; do not scatter the material. Use water spray or fog; do not use straight streams. For fire involving tanks or car/trailer loads, fight the fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after the fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tanks. Always stay away from tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from the area and let the fire burn. Run-off from fire control or dilution water may be corrosive and/or toxic, and it may cause pollution. If the situation allows, control and properly dispose of run-off (effluent).
For fire involving tanks or car/trailer loads, fight the fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after the fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tanks. Always stay away from tanks engulfed in fire.
Run-off from fire control or dilution water may be corrosive and/or toxic, and it may cause pollution. If the situation allows, control and properly dispose of run-off (effluent).
For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from the area and let the fire burn.
/Colchicine/ is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.; View all

4.8 FirePotential: Slight.

4.9 Safety Profile: experimentally by most routes. Human systemic effects: aplastic anemia, blood pressure depression, body temperature decrease, changes in kidney tubules, dyspnea, flaccid paralysis without anesthesia, gastrointestinal effects, kidney damage and hemorrhaging, muscle contraction or spasticity, muscle weakness, nausea or vomiting, respiratory stimulation, and somnolence. An experimental teratogen. Experimental reproductive effects. A severe eye irritant. Human mutation data reported. Inhibits the formation of microtubules and thus impairs cell division. When heated to decomposition it emits toxic fumes of NOx.

4.10 Caution Statement: Missing Phrase - N15.00950417-P201-P280-P304 + P340 + P310-P305 + P351 + P338 + P310-P308 + P313

4.10 Formulations/Preparations: Grades: technical; United States Pharmacopeia.
Colchineos
Colchisol
Colcin
Colsaloid
Condylon
Oral: Tablets: 0.6 mg (Colchicine Tablets). NOTE: Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name.

4.11 Incompatibilities: Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, mineral acids. Keep away from light. Colchicine Preparation Products And Raw materials Raw materials ColchicineSupplier

4.12 WGK Germany: 3

4.12 RTECS: GH0700000

4.12 Protective Equipment and Clothing: Eye, skin, gastrointestinal and/or respiratory tract irritation.

4.13 Report: EPA Extremely Hazardous Substances List. EPA Genetic Toxicology Program. Reported in EPA TSCA Inventory.

4.14 Skin, Eye, and Respiratory Irritations: Eye, skin, gastrointestinal and/or respiratory tract irritation.

4.15 Safety: A human poison by ingestion and intravenous routes. Poison experimentally by most routes. Human systemic effects: aplastic anemia, blood pressure depression, body temperature decrease, changes in kidney tubules, dyspnea, flaccid paralysis without anesthesia, gastrointestinal effects, kidney damage and hemorrhaging, muscle contraction or spasticity, muscle weakness, nausea or vomiting, respiratory stimulation, and somnolence. An experimental teratogen. Experimental reproductive effects. A severe eye irritant. Human mutation data reported. Inhibits the formation of microtubules and thus impairs cell division. When heated to decomposition it emits toxic fumes of NO_x.
Hazard Codes:?T+,T
Risk Statements: 26/28?
R26/28:Very toxic by inhalation and if swallowed.
Safety Statements: 13-45?
S13:Keep away from food, drink and animal foodstuffs.?
S45:In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)
RIDADR: UN 1544 6.1/PG 1
WGK Germany: 3
RTECS: GH0700000
HazardClass: 6.1
PackingGroup: I; View all

4.16 Sensitive: Light Sensitive

4.17 Specification: ? Colchicine (CAS NO.64-86-8), its Synonyms are 7-alpha-H-Colchicine ; 7alphaH-Colchicine ; AI3-31149 ; Acetamide, N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-yl)-, (S)- ; Benzo(a)heptalen-9(5H)-one, 7-acetamido-6,7-dihydro-1,2,3,10-tetramethoxy- ; Acetamide, N-((7S)-5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-yl)- ; Acetamide, N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-yl)-, (S)- . It is odorless or nearly odorless pale yellow needles or powder that darkens on exposure to light.

4.18 Toxicity: LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson); in mice (mg/kg): 4.13 i.v. (Beliles)

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 2

Germ cell mutagenicity, Category 1B

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Danger
Hazard statement(s)	H300 Fatal if swallowed H340 May cause genetic defects
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood. P280 Wear protective gloves/protective clothing/eye protection/face protection.
Response	P301+P310 IF SWALLOWED: Immediately call a POISON CENTER/doctor/\u2026 P321 Specific treatment (see ... on this label). P330 Rinse mouth. P308+P313 IF exposed or concerned: Get medical advice/ attention.
Storage	P405 Store locked up.
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

View all

6. NMR Spectrum

13C NMR : in CDCl3

1H NMR : 400 MHz in CDCl3

IR : KBr disc

IR : nujol mull

Mass

Mass spectrum (electron ionization)

7. Synthesis Route

64-86-8Total: 1 Synthesis Route

186581-53-3

33530-04-0 1 Suppliers

64-86-8 358 Suppliers

7336-36-9 7 Suppliers

Literatures:
Chommadov, B. Ch.; Yusupov, M. K.; Aslanov, Kh. A. Chemistry of Natural Compounds, 1991 , vol. 27, # 1 p. 58 - 61 Khimiya Prirodnykh Soedinenii, 1991 , # 1 p. 67 - 71
Yield: null

8. Other Information

8.0 Merck: 14,2471

8.1 BRN: 2228813

8.2 Alkaloids: Colchicine is a kind of alkaloid extracted from the crom or seed of the lily family plants, Colchicum autumnale, and is naturally presented in the Liliaceae Garland and Iphigenia with the contents being 0.11% and 0.1%. It is pale yellow needle crystals. It has slight odor and bitter taste with the melting point being 157 ℃. It is soluble in cold water, alcohol, chloroform and formaldehyde with poor solubility in hot water and is not easily soluble in benzene and ether. It is almost insoluble in petroleum ether with the pH of its 0.5% solution being 5.9. Hydrolysis with ammonia can reduce the toxicity. Colchicine is known to inhibit cell mitosis and has anti-tumor effect. In 1889, Italian scholar Pernice had first discovered the effect of colchicine on mitosis. He had described the metaphase of the lining cells in the stomach and intestines of dogs can be blocked colchicine with spindle being damaged and chromosome action paralyzed as well as a large number of abnormal mitotic cells existing in their metaphase. This abnormal division caused by the colchicine is known as colchicine mitosis (referred as the C mitosis). In the mutagenesis analysis of karyotyping and polyploid, colchicine is a most widely used chemicals. Its water concentration has a positive correlation with its action role. The higher the concentration is, the stronger the effect will be. Various kinds of plants and different organizations are known to have different response to colchicine. Generally, for young and rapidly divided organizations (e.g. germ of germinating seeds), the processing time can be shorter and the concentration should be lower; on the contrary, the processing time can be longer and the concentration should be higher. The effective concentration of colchicine treatment is 0.01 to 0.4% with the concentration of 0.2% having the mostly wide range. For example, if we drop 0.2 to 0.4% of colchicine solution on the diploid watermelon seedlings growing point once a day for four consecutive days, and keep the shade and humidity, you can induce tetraploid watermelon. For cereal crops such as rice, you can have robust seedling with four or more leaves cut an incision in the root neck with the degree within not cutting the growing point and immerse it into the 0.025 to 0.05% colchicine solution, submerge the incision, you can also obtain the tetraploid plants after 8 to 14 days (20 ℃). Currently, the colchicine is widely used for the chromosome doubling for haploid plants obtained from the culture of anther (powder), ovary culture.; View all

8.3 Anti-gout drug: Colchicine has a good efficacy in treating acute gout and can quickly relieve pain and can prevent the onset of arthritis with its mechanism of action related to the inhibition of white blood cells and proliferation activities and the effect on lysosomal release.
The pharmacological effects of this product are through reducing activity and phagocytosis of leukocytes in the inflammatory tissue and reducing the inflammation caused by uric acid crystals, and thus playing effects of inflammation, swelling and pain effect, therefore it has selective anti-inflammatory effect on the acute gouty arthritis. In addition the product is also a kind of mitosis toxins with strong inhibitory effect of cell division, making the cells stopped in their division time and leading to tumor cell death, and therefore being used for cancer treatment. This product is easily absorbed after oral administration with 30% binding to plasma proteins and the plasma concentration reaching peak at 0.5 to 2 hours after oral administration. The plasma concentration peak after oral administration of 2mg is about 2.2ng/ml. It can play its efficacy at 12 hours after the administration in the case of acute gout and the efficacy can sustain 50 to 70 hours. The drug concentration in the isolated neutrophils is higher than the plasma concentrations and can maintain for as long as 10 days. This product is mostly metabolized by the liver with the metabolite and the prototype drug being excreted by the bile, further being reabsorbed through the intestinal tract with the unabsorbed part being discharged by the gut. The rest, about 10% to 20%, can be excreted through renal via urine.
This product does not affect the formation, dissolution and excretion of uric acid salt thereby has no effect on lowering the blood uric acid content. It is clinically used for the treatment of acute gouty arthritis attack, prevention of recurrent episodes of acute gouty arthritis, familial Mediterranean fever, leukemia, skin cancer, Hodgkin's disease, and aplastic anemia. It can also applied to the specific treatment of M cycle of various kinds of malignant diseases such as the breast cancer, lung cancer, esophageal cancer, cervical cancer, nasopharyngeal carcinoma, Hodgkin's disease, chronic myelogenous leukemia, and skin cancer.; View all

8.4 Side effects: The adverse reaction has significant correlation with the dosage.
1. Gastrointestinal reactions: nausea, abdominal pain, diarrhea, vomiting and loss of appetite are common early side effects with the incidence being up to 80%. In severe cases, there may be dehydration and electrolyte imbalance. Upon such kind of performance, the drug should be immediately discontinued. Patients of long-term usage can get severe hemorrhagic gastroenteritis or malabsorption syndrome.
2. The blood system reactions: long-term medication can cause agranulocytosis, thrombocytopenia, aplastic anemia, and sometimes threaten the life.
3. Other toxic reactions; it is mainly manifested as urinary tract irritation symptoms such as urinary frequency, urgency, dysuria, hematuria, oliguria, or even renal failure. There may also be symptoms such as stomach, throat or skin burning sensation, and fever, bloody diarrhea, mental changes, myasthenia gravis, and respiratory depression.
4. During the period of taking colchicine, we should pay attention to check blood and liver and kidney function. Patients of hematopoietic dysfunction, liver and kidney damage, heart disease and severe gastrointestinal disease should administer with caution. Pregnant women should be disabled.
5. Muscles, peripheral neuropathy: proximal muscle weakness, and elevated serum creatine kinase; there may also be peripheral nerve axonal polyneuropathy at the same time of damaged muscle cells, manifested as numbness, tingling and weakness; muscle neuropathy is rare, often occurs for people of long-term use in the prevention of gout and those with mild renal insufficiency.; View all

8.5 Dosage and administration: Tablets: 0.5 mg per tablet; injection: 1mg, 2mg.
1. for the treatment of acute gout: for adult who orally administers tablets, apply the first dose of 0.5~1 mg, then take 0.5~0.6 mg every 1 to 2 hours until the joint symptoms or gastrointestinal symptoms get alleviated when you can discontinue the treatment. Usually a total dose of 4~10 mg can play obvious efficacy. Note that the patients should administer the drug as early as possible to get excellent efficacy during the acute phase of medication. If the patients take intravenous injection with the first dose being 1~2mg, slowly inject with 20 mL of saline with the time of being no less than five minutes. If necessary, apply intravenous injection every 6 to 12 hours for 0.5~1 mg until it works with the total dose of 4~5 mg/d. Intravenous injection can give a better efficacy than oral administration, and can also significantly reduce the gastrointestinal reactions.
2. for the prevention of acute gout: Adults should take 0.5~0.6 mg of tablet per time with 2 times daily or intravenous injection of 1~2mg/d. 3. For the diagnosis test of gout: If the acute joints symptom gets alleviated after treatment, this will help confirm the diagnosis.; View all

8.6 Hazardous characteristics: Colchicine itself has a small toxicity, but after absorption, it can be metabolized (oxidized) in vivo to become the oxydicolchicine of a strong toxicity. It has a strong irritation effect on the digestive tract and can inhibit the blood cells, causing neutropenia deficiency and aplastic anemia. It can also cause paralysis on the nerve center and smooth muscle, resulting in vasodilation, and respiratory center paralysis and death. The human lethal dose of colchicine is 6mg~7mg. Mouse oral-LD ??was 66.6mg/kg; LD50-intraperitoneal injection of mice is 3.5mg/kg. LD50-subcutaneous injection of rat is 4mg/kg.
This product has been applied for treating acute gout for a long time. Later, it was found that it has a strong inhibitory effect on the cell division. Medically, it has been applied to the treatment of various cancers, such as breast cancer, cervical cancer, esophageal cancer, skin cancer, and chronic myelogenous leukemia. However, due to the high colchicine toxicity, in order to reduce the toxicity and improve the efficacy, people has modified the structure of colchicine with the toxicity of the resulting compounds being reduced, such as colchicine amine (TMCA, I), colchicine methylamine (Demecolcine II), it has now been used clinically.
Colchicine poisoning has a certain incubation period with symptoms often happening at 3d~6d after oral administration or injection. Symptoms include throat burning, nausea, vomiting, abdominal pain, diarrhea, watery stools, hematuria, urine retention, numbness, aching limbs, muscle cramps, hair loss, dilated pupils, and convulsion, paralysis of the central nervous system, and respiratory depression and death. In addition, it can also produce local reactions such as when the drug liquid is leaked out from the blood vessel upon injection, local tissue necrosis can occur. Poisoning is usually caused by ingestion or drug overdose. There are also individual cases in which people take it for suicide. The method of treatment is mainly symptomatic treatment. Patients of swallowing colchicine or patients of colchicine poisoning should be prohibited for the use of oxidants such as potassium permanganate to avoid generating a large number of colchicine oxide in the body which further increases the toxicity.; View all

8.7 Chemical Properties: It is pale yellow crystal or crystalline powder with bitter taste and the color being changed upon exposure to light.. M.p. is 157 ℃ (recrystallized from ethyl acetate), specific rotation [α] 17D-429 ° (1.72%, water),-121° (0.9%, chloroform). It has the maximum absorption wavelengths being 243nm and 350.5 nm in ethanol. This product is easily soluble in water, ethanol and chloroform, soluble in benzene and ether, but insoluble in petroleum ether. The 0.5% solution of this product is acidic. LD50 (mouse, intraperitoneal) is 6.1mg/kg.

8.8 Uses: It can be used for the study of plant genetics; used as selenium reagent; clinically as anticancer drugs.
The product is a typical mitosis toxin. It can be used for treating acute gout and breast cancer. It can also be used as selenium reagent, for being applied to plant genetics and cancer research.
It is a kind of antineoplastic agents and anti-gout for being used for the treatment acute gout and for the treatment of tumors

8.9 Application in Acute Gouty Arthritis

Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset.
Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis.
Colchicine should be reserved for patients with insufficient relief, intolerance, or contraindications to NSAIDs.
The usual oral colchicine dose is 1 mg initially, followed by 0.5 mg every 1 hour until the joint symptoms subside, the patient develops abdominal discomfort or diarrhea, or a total dose of 8 mg has been given.
IV colchicine should be avoided because it is associated with serious adverse effects (e.g., bone marrow suppression, tissue necrosis from local extravasation, disseminated intravascular coagulation, hepatocellular toxicity, and renal failure). If considered necessary, the recommended initial IV dose is 2 mg (if renal function is normal) diluted in 10 to 20 mL of normal saline administered slowly over 10 to 20 minutes in a secure, freeflowing IV line to avoid extravasation. This may be followed by two additional doses of 1 mg each at 6-hour intervals, with the total dose not exceeding 4 mg. After a full IV course, patients should not receive colchicine by any route for at least 7 days.

View all

8.10 Production method: This product is a kind of alkaloid extracted from the crom or seed of the lily family plants, Colchicum autumnale. The Colchicum autumnale powder was heated under reflux with 85% ethanol extraction for 4h, the resulted ethanol solution was concentrated under reduced pressure to a semi-gum, dilute with distilled water, with 10% sulfuric acid acidified filtrate with extraction by chloroform, and then concentrate the chloroform extract, the resulted crude colchicine obtained by crystallization was subject to re-crystallization to obtain the finished product. Calculated from the Colchicum autumnale powder, the total yield is 0.15%. In foreign countries, it is mostly extracted from the crom of the Liliaceae Colchicum genus Colchicum bulbs.
Take the bulbs and seeds of Iphigenia indica or Colchicum autumnale as raw material; obtain the final product with ethanol extraction and refining.

8.11 Category: toxic substances

8.12 Toxicity grading: toxic

8.13 Acute toxicity: intravenous-rat LD50: 1.6 mg/kg; Oral-Mouse LD50: 5.886 mg/kg

8.14 Irritation data: eyes-rabbit 1%/3 days Severe

8.15 Flammability and hazard characteristics: combustible with fire causing decomposition into toxic nitrogen oxide fumes

8.16 Storage properties: warehouse: cold, ventilated and dry; and food raw materials stored separately

8.17 Extinguishing media: Water, carbon dioxide, dry, sandy soil

8.18 Description: Colchicine is a pale-yellow powder that is obtained from various species of Colchicum, primarily Colchicum autumnale L. Its total chemical synthesis has been achieved, but the primary source of colchicine currently remains alcohol extraction of the alkaloid from the corm and seed of C. autumnale L. It darkens on exposure to light and possesses

8.19 Chemical Properties: Yellow Solid

8.20 Chemical Properties: Colchicine is a pale yellow powder. It has little or no odor. It darkens on contact with light.

8.21 Physical properties: Appearance: colchicine exists in white or light-yellow crystal powder with no smell, and it is seldom prone to absorb moisture. Melting point: it becomes dark when it is exposed to light, and it melts at 87–89?°C. Solubility: this product is soluble in chloroform or ethanol and it dissolves in water. However, the semihydrate crystal can form in certain concentrations. The product is hardly soluble in ether. Specific optical rotation: ?121° (0.9?g/100?mL, chloroform, 589.3?nm, 17?°C).

8.22 History: Meadow saffron (Colchicum) is recorded to treat rheumatic swelling on ancient Egyptian medical papyrus in 1500 B.C.. According to De Materia Medica written by Pedanius Dioscorides in the first century, extract of Meadow saffron is used in treating gout. London Pharmacopoeia in 1618 recorded that colchicine is also applied to treat gout.
In 1820, the ingredient was first isolated by the French chemist P.S. Pelletier and J.B. Caventou. In 1833, it was purified and named by Geiger. Michael Dewar guessed that there are two seven-membered rings in colchicine in 1945. Murray Vernon King et al. determined the structure of colchicine by X-ray diffraction in 1952. In 1959, Albert Eschenmoser integrated the product successfully
Colchicine tablet and raw material are approved mostly in domestic in 2010. The tablet produced by Taiwan manufacturers is approved for being listed in mainland of China in 2012. The raw material made by Indian obtained the approval in 2013. There are three kinds of colchicine approved by FDA: with the combination of probenecid, it is prior to be approved. The others are tablet (2009) and capsule (2014).; View all

8.23 Uses: Colchicine is present in the poisonous autumncrocus (meadow saffron). It is the major alkaloid of Colchicum autumnale L. and Liliaceae. It was used in poison potions in theancient kingdom of Colchis (Greece). It isused therapeutically as an antineoplast, for thesuppression of gout, and in the treatment ofMediterranean fever. It is used in plant studiesfor doubling chromosome groups.

8.24 Uses: Binds specifically with tubulin thus interfering with microtubule organization.

8.25 Uses: antimitotic, antigout agent

8.26 Uses: An antimitotic agent that disrupts microtubles by binding to tubulin and preventing its polymerization. Stimulates the intrinsic GTPase activity of tubulin. Induces apoptosis in several normal and t umor cell lines and activates the JNK/SAPK signaling pathway.

8.27 Uses: anti-inflammatory agent, mitosis inhibitor

8.28 Uses: For treatment and relief of pain in attacks of acute gouty arthritis.

8.29 Uses: In research in plant genetics (for doubling chromosomes).

8.30 Definition: An alkaloid plant hormone.

8.31 Definition: colchicine: An alkaloid derivedfrom the autumn crocus, Colchicumautumnale. It inhibits cell division.Colchicine is used in genetics, cytology,and plant breeding research andalso in cancer therapy to inhibit celldivision.

8.32 Indications: Colchicine, an alkaloid obtained from the autumn crocus, has long been used and is relatively selective for the treatment of acute gouty arthritis. Unlike many of the newer agents for use in gout, colchicine has minimal effects on uric acid synthesis and excretion; it decreases inflammation associated with this disorder. It is thought that colchicine somehow prevents the release of the chemotactic factors and/or inflammatory cytokines from the neutrophils, and this in turn decreases the attraction of more neutrophils into the affected area .The ability of colchicine to bind to leukocyte microtubules in a reversible covalent complex and cause their depolymerization also may be a factor in decreasing the attraction of the motile leukocytes into the inflamed area.

8.33 Biological Functions: Acting on polymorphonuclear leukocytes and diminishing phagocytosis, it inhibits the production of lactic acid, causing an increase in the pH of synovial tissue and, thus, a decrease in urate deposition, because uric acid is more soluble at the higher pH. Additionally, colchicine inhibits the release of lysosomal enzymes during phagocytosis that also contributes to the reduction of inflammation. Because colchicine does not lower serum urate levels, it has been found to be beneficial to combine colchicine with a uricosuric agent, particularly probenecid. It is a potent drug, being effective at doses of approximately 1 mg, but doses as small as 7 mg have caused fatalities.

8.34 General Description: Colchicine is an alkaloid isolated from the dried corns andseeds of Colchicum autumnale L., commonly known as autumncrocus or meadow saffron.It is specifically indicated for acute treatment of goutyarthritis because of its ability to block the production and releaseof the CCF that mediates the inflammatory responsebecause of urate crystals, a mechanism different fromcolchicine’s antimitotic action, which is being investigatedfor its anticancer properties. It is often quite effective inaborting an acute gouty attack if given within the first 10 to12 hours after the onset of arthritis.

8.35 General Description: Odorless or nearly odorless pale yellow needles or powder that darkens on exposure to light. Used to treat gouty arthritis, pseudogout, sarcoidal arthritis and calcific tendinitis.

8.36 Air & Water Reactions: Slowly hydrolyzed in acidic solution, but unbuffered solutions are stable at 68°F for at least six months. Isomerizes on exposure to ultraviolet radiation.

8.37 Reactivity Profile: Colchicine darkens on exposure to light. Incompatible with strong oxidizing agents. Also incompatible with mineral acids .

8.38 Hazard: As little as 20 mg may be fatal if ingested.

8.39 Health Hazard: Colchicine is a highly toxic alkaloid. Thetarget organs are the lungs, kidney, gastrointestinal tract, and blood. The toxiceffects include drowsiness, nausea, hypermotility, diarrhea, lowering of body temperature, lowering of blood pressure, tremors,convulsions, and respiratory distress. Chronicingestion may cause aplastic anemia andhemorrhage.
LD50 value, oral (mice): 5.9 mg/kg
Colchicine solution at 10,000 ppm concentration caused severe irritation whenapplied repeatedly to rabbits’ eyes. Colchicine produced teratogenic effects in testanimals. It caused fetal death, cytologicalchanges, and developmental abnormalitiesin hamsters, rabbits, domestic animals,and mice. It tested positive to in vitromammalian nonhuman micronucleus andD. melanogaster — nondisjunction tests formutagenicity (U.S. EPA 1986; NIOSH1986).

8.40 Health Hazard: Colchicine is classified as super toxic. Probable oral lethal dose in humans is less than 5 mg/kg, i.e. less than 7 drops for a 70 kg (150 lb.) person. Death results from respiratory arrest. The fatal dose varies considerably; as little as 7 mg of Colchicine has proved fatal.

8.41 Fire Hazard: Stable.

8.42 Biological Activity: Plant-derived alkaloid that binds to tubulin and depolymerizes microtubules.

8.43 Biochem/physiol Actions: Colchicine interacts with albumin and binds to tubulin. Its association with tubulin impacts autophagic vacuole fusion with lysosomes. It inhibits tyrosine kinases and phospholipases. Colchicine may be useful for treating acute coronary syndromes. It is prescribed for treating rheumatologic conditions including familial mediterranean fever (FMF) and acute gouty arthritis.

8.44 Mechanism of action: Colchicine is rapidly absorbed after oral administration and tends to concentrate in the spleen, kidney, liver, and gastrointestinal tract. Leukocytes also avidly accumulate and store colchicine even after a single intravenous injection. Since colchicine can accumulate in cells against a concentration gradient, it is postulated that an active transport process may be involved in its cellular uptake. The drug is metabolized, primarily in the liver, by deacetylation. Fecal excretion plays a major role in colchicine elimination, since it and its metabolites are readily secreted into the bile. Only about 15 to 30% of the drug is eliminated in the urine except in patients with liver disease; urinary excretion is more important in these individuals.

8.45 Pharmacology: The drug can be given intravenously as well as orally, but care must be exercised, since extravasated drug may result in local sloughing of skin and subcutaneous tissues. Relief of pain and inflammation usually occurs within 48 hours. Small doses of colchicine can be used during asymptomatic periods to minimize the reappearance or severity of acute attacks. It should be used with caution in patients with preexisting compromised heart, kidney, gastrointestinal tract, and liver disease. Diarrhea, nausea, vomiting, and abdominal pain are the major limiting side effects that ultimately determine the tolerated dosage. These symptoms occur in approximately 80% of patients who take colchicine, especially in those taking high dosages. The hepatobiliary recycling of colchicine and its antimitotic effect on cells that are rapidly turning over, such as those of the intestinal epithelium, account for its gastrointestinal toxicity. Gastrointestinal symptoms generally intervene before the appearance of more serious toxicity and thereby provide a margin of safety in drug administration. Ingestion of large doses of colchicine may be followed by a burning sensation in the throat, bloody diarrhea, shock, hematuria, oliguria, and central nervous system (CNS) depression.; View all

8.46 Pharmacokinetics: Colchicine is absorbed on oral administration, with peak plasma levels being attained within 0.5 to 2 hours after dosing. Plasma protein binding is only 31%. It concentrates primarily in the intestinal tract, liver, kidney, and spleen and is excreted primarily in the feces, with only 20% of an oral dose being excreted in the urine. It is retained in the body for considerable periods of time, being detected in the urine and leukocytes for 9 to 10 days following a single dose.

8.47 Anticancer Research: It is a natural toxic secondary metabolite, extracted from Colchicum genus plants. Itprevents gastric cancer by upregulating the dual specificity phosphatase 1 (DUSP1)gene. It is also reported to upregulate transforming growth factor beta 2 (TGF-β2)and A-kinase anchoring protein 12 (AKAP12) in hepatocellular carcinoma (Singhet al. 2016b).

8.48 Clinical Use: The major use of colchicine is as an antiinflammatory agent in the treatment of acute gouty arthritis; it is not effective in reducing inflammation in other disorders. It also can be used to prevent attacks. Since colchicine is so rapidly effective in relieving the acute symptoms of gout (substantial improvement is achieved within hours), it has been used as a diagnostic aid in this disorder. Therapy with colchicine is usually begun at the first sign of an attack and is continued until symptoms subside, adverse gastrointestinal reactions appear, or a maximum dose of 6 to 7 mg has been reached.

8.49 Side effects: Colchicine may produce bone marrow depression, with long-term therapy resulting in thrombocytopenia or aplastic anemia. At maximum dose levels, GI disturbances (e.g., nausea, diarrhea, and abdominal pain) may occur. Acute toxicity is characterized by GI distress, including severe diarrhea resulting in excessive fluid loss, respiratory depression, and kidney damage. Treatment normally involves measures that prevent shock as well as morphine and atropine to diminish abdominal pain. A number of drug interactions have been reported. In general, the actions of colchicine are potentiated by alkalinizing substances and are inhibited by acidifying drugs, consistent with its mechanism of action of increasing the pH of synovial fluid. Responses to CNS depressants and to sympathomimetic drugs appear to be enhanced. Clinical tests may be affected; most notably, elevated alkaline phosphatase and SGOT (serum glutamate oxaloacetate transaminase) values and decreased thrombocyte values may be obtained.; View all

8.50 Safety Profile: experimentally by most routes. Human systemic effects: aplastic anemia, blood pressure depression, body temperature decrease, changes in kidney tubules, dyspnea, flaccid paralysis without anesthesia, gastrointestinal effects, kidney damage and hemorrhaging, muscle contraction or spasticity, muscle weakness, nausea or vomiting, respiratory stimulation, and somnolence. An experimental teratogen. Experimental reproductive effects. A severe eye irritant. Human mutation data reported. Inhibits the formation of microtubules and thus impairs cell division. When heated to decomposition it emits toxic fumes of NOx.

8.51 Potential Exposure: Colchicine is a drug used to treat gouty arthritis, pseudogout, sarcoidal arthritis; and calcific tendonitis.

8.52 Veterinary Drugs and Treatments: In veterinary medicine, colchicine has been proposed as a treatment in small animals for amyloidosis. For colchicine to be effective, however, it must be given early in the course of the disease and it will be ineffective once renal failure has occurred. At the time of writing, no conclusive evidence exists for its efficacy for this indication in dogs.
Colchicine has also been proposed for treating chronic hepatic fibrosis presumably by decreasing the formation and increasing the breakdown of collagen.

8.53 Environmental Fate: Colchicine binds to tubulin and prevents its polymerization into microtubules, subsequently disrupting microtubule function. Consequently, it alters nuclear structure, intracellular transport, and cytoplasmic motility, ultimately causing cell death. Colchicine is a potent inhibitor of cellular mitosis.

8.54 Metabolism: Metabolism occurs primarily in the liver, with the major metabolite being the amine resulting from amide hydrolysis.

8.55 Shipping: UN1544 Alkaloids, solid, n.o.s. or Alkaloid salts, solid, n.o.s. poisonous, Hazard Class: 6.1; Labels: 6.1- Poisonous materials, Technical Name Required. UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials

8.56 Purification Methods: Commercial material contains up to 4% desmethylcolchicine. Purify colchicine by chromatography on alumina and eluting with CHCl3 [Ashley & Harris J Chem Soc 677 1944]. Alternatively, an acetone solution on alkali-free alumina has been used, and eluting with acetone [Nicholls & Tarbell J Am Chem Soc 75 1104 1953]. It crystallises as yellow needles from EtOAc or CHCl3 with solvent of crystallisation which can be removed at ~70o. It is soluble in Et2O (0.5%), *C6H6 (1%) and H2O (4%). It is sold as “Colgout” for the treatment of gout and binds to tubulin. [Schreiber et al. Helv Chim Acta 44 540 1961, Scott et al. Tetrahedron 21 3605 1965, van Tamelen et al. Tetrahedron 14 8 1961, Beilstein 14 IV 946.]

8.57 Toxicity evaluation: No information is currently available on breakdown in soil, groundwater, or surface water. Colchicine alkaloids withstand storage, drying, and boiling.
Ingestion is the most common route of both accidental and intentional exposure to colchicine. It is available as an oral tablet and solution for injection.

8.58 Incompatibilities: Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, mineral acids. Keep away from light.

8.59 Usage: Colchicine is used as an anti-inflammatory agent for long-term treatment of beh?et's disease. It is used for constipation-predominant irritable bowel syndrome in women, and for treatment of severe or persistent aphthous stomatitis (canker sores).

8.60 Usage: Colchicine is most commonly used to treat gout. It is an inhibitor of microtubule polymerization which blocks chromosome segregation during meiosis. Consequently, it is used to induce polyploidy (tetraploid) in plant cells. It is an antimitotic agent that disrupts microtubules by binding to tubulin and preventing its polymerization. Stimulates the intrinsic GTPase activity of tubulin. Induces apoptosis in several normal and tumor cell lines and activates the JNK/SAPK signaling pathway.

9. Computational chemical data

Molecular Weight: 399.437g/mol
Molecular Formula: C₂₂H₂₅NO₆
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 399.16818752
Monoisotopic Mass: 399.16818752
Complexity: 740
Rotatable Bond Count: 5
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 6
Topological Polar Surface Area: 83.1
Heavy Atom Count: 29
Defined Atom Stereocenter Count: 1
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADceB6OAAAAAAAAAAAAAAAAAAAAAAAAAAwAAAABggAAAABAAAAHgAQAAAADCzBmAYyBoLABACIAqFSEAKCCAAgIAAAiIBOiMgNJyKEsR6EMCIl1hWKqYeQ8P8OoAABCAAYQABAAAIQADCAAAAAAAAAAA==

10. Question & Answer

What Are the Mechanisms, Activities, and Side Effects of Colchicine? Jul 24 2023
General Description Colchicine is a versatile medication known for its ability to bind to tubulins, disrupting the assembly and polymerization of microtubules. This unique mechanism of action results ..
What is Colchicine and How is it Used? Jan 11 2022
Derived from the autumn crocus, Colchicum autumnale, or the glory lily, Gloriosa superba, Colchicine has a long history of use for swelling and various types of inflammatory arthritis dating back to t..
Can Colchicine Be Used Safely for Acute Gout Attacks? Nov 04 2019
If you have ever experienced an acute gout attack, you are probably familiar with the medication Colchicine. As one of the main drugs used for pain relief and anti-inflammatory purposes during acute g..

11. Recommended Suppliers

Global347SuppliersView all >>

Anhui Ruihan Technology Co.,Ltd Diamond member

1YR

Products:Chemical;Pharmaceutical Raw Materials
Tel:00-86-15956513393
Email:viola@anhuiruihan.com

99% Purity Colchicine Raw Powder CAS 64-86-8 Colchicum Autumnale Extract

Purity:99%Packing: 200kg/bag FOB
Price: 30 USD/kg
Time: 2023/10/03

Inquire

Hebei Ruiyao Biotechnology Co., Ltd Diamond member

2YRS

Products:Cosmetic Grade Chemical Raw Materical,Chemicals Raw Materials,API,Pharmaceutical Intermediates,Organic Chemicals
Tel:0311-88180881-19932787653
Email:sale06@ruiyaobio.com

China factory Colchicine Hot sales 99% White powder

Purity:99%Packing: 200kg/bag FOB
Price: 25 USD/kg
Time: 2023/09/28

Inquire

Hebei Crovell Biotech Co. Ltd Diamond member

3YRS

Products:Cosmetic Raw Materials,solvents,etc.
Tel:86-311-66562153
Email:breeduan@crovellbio.com

Factory supply Colchicine Cas 64-86-8 from China

Purity:99%Packing: 200kg/bag FOB
Price: 10 USD/kilogram
Time: 2023/09/28

Inquire

Hebei Miaoou Technology Co., Ltd. Diamond member

1YR

Products:14188-81-9 28578-16-7PMK BMK 20320-59-6 5449-12-7 125541-22-2 1451-83-8 236117-38-7 5337-93-9 5F 5CL 6CL SGT263 JWH018 2F 4F ETI EU FLU ALP
Tel:+86-0311-15383932942
Email:grace@hbmiaoou.com

China factory Colchicine Hot sales 99% White powder CAS 64-86-8

Purity:99%Packing: 200kg/bag FOB
Price: 100 USD/kg
Time: 2023/09/28

Inquire

Hebei Bester Biotechnology Co., Ltd. Diamond member

1YR

Products:pmk powder ;pmk oil ;bmk powder ;bmk oil ;Protonitazene hcl ; Bromazolam ; Metonitazene; 2-Bromo-4'-methylpropiophenone ;
Tel:+86-180-32431584
Email:amy@chbbest.com

CAS 64-86-8 Colchicine