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コルヒチン
コルヒチン (≦5%酢酸エチル含む) · (7S)-1,2,3,10-テトラメトキシ-7α-(アセチルアミノ)-5,6,7,9-テトラヒドロベンゾ[a]ヘプタレン-9-オン · コルチシン · (7S)-(-)-コルヒチン · N-[[(7S)-1,2,3,10-テトラメトキシ-9-オキソ-5,6,7,9-テトラヒドロベンゾ[a]ヘプタレン]-7α-イル]アセトアミド · コルヒネオス · コルキシン · (7S)-コルキシン
識別子と物理属性
| CAS No. | 64-86-8 |
|---|---|
| 分子式 | C22H25NO6 |
| 平均分子量 | 399.4 g/mol |
| 単同位体質量 | 399.16818752 g/mol |
| SMILES | COc1cc2c(c(OC)c1OC)-c1ccc(OC)c(=O)cc1[C@@H](NC(C)=O)CC2 |
| InChIKey | IAKHMKGGTNLKSZ-INIZCTEOSA-N |
| PubChem CID | 6167 |
| ChEMBL | CHEMBL107 |
| ChEBI | CHEBI:27882 |
| EC No. | 200-598-5 |
| DTXSID | DTXSID5024845 |
| 現地名 | コルヒチン |
化学・物理的性質
| XLogP | 1 |
|---|---|
| 極性表面積 | 83.1 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 6 |
| 回転可能結合数 | 5 |
| 重原子数 | 29 |
| 形式電荷 | 0 |
| 複雑度 | 740 |
| 物質分類 | Teratogens-> NIOSH Emergency Response Categories |
| 医薬品 | Pharmaceuticals -> Listed in ZINC15 |
| pH | pH of 0.5% solution: 5.9 |
| SpringerMaterials Properties | Crystal structure |
| LogP（分配係数） | log Kow = 1.03 |
| 臭い | Odorless or nearly so |
| Color/Form | Pale yellow scales or powderpale yellow needles when crystallized from ethyl acetateYellow plates from water + 1/2 mol of water of crystallizationyellow crystals from benzene |
| 溶解度 | greater than or equal to 100 mg/mL at 70 °F (NTP, 1992)1 g dissolves in 22 mL water, 220 mL ether, 100 mL benzenefreely sol in alcohol or chloroformpractically insoluble in petroleum etherSOL IN METHANOLSLIGHTLY SOL IN CARBON TETRACHLORIDEAt 25 °C, 4.5 g/100 g waterH2O: 10 mg/mL45g/L(20℃) |
| Human Drugs | Breast FeedingLactationMilk, HumanAntigout AgentsAntimitotic AgentsGout SuppressantsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicinePharmaceuticals |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| 沸点 | 407 °C @760 [mm Hg]522.37°C (rough estimate) |
| Decomposition | When heated to decomposition, colchicine emits toxic fumes of carbon monoxide, carbon dioxide, and nitrogen oxides. |
| 融点 | 150-160 °C (dec.)(lit.) |
| 比旋光度 | -250 º (c=1, alcohol) |
| 密度 | 1.2770 (rough estimate) |
| 屈折率 | 1.5614 (estimate) |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 12.36(at 20℃) |
| 色 | 緑がかかった白から黄色 |
| Merck | 14,2471 |
| BRN | 2228813 |
| ヘンリー定数 | 5.5×1011 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 3 |
| 安定性 | 安定。光に敏感。強力な酸化剤とは相容れない。 |
| 主な用途 | 農業 |
| 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 |
| InChIKey | IAKHMKGGTNLKSZ-INIZCTEOSA-N |
| SMILES | COC1=CC=C2C(=CC1=O)[C@H](CCc3cc(OC)c(OC)c(OC)c23)NC(C)=O |
| LogP（分配係数） | 1.300 |
| CAS データベース | 64-86-8(CAS DataBase Reference) |
| NISTの化学物質情報 | Colchicine(64-86-8) |
| EPAの化学物質情報 | Colchicine (64-86-8) |
化学的特性
Colchicine is a pale yellow powder. It has little or no odor. It darkens on contact with light.
安全性と法規制
| GHS 分類 | DangerH300: Fatal if swallowed [Danger Acute toxicity, oral]P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)H300+H330 (25.9%): Fatal if swallowed or if inhaled [Danger Acute toxicity, oralacute toxicity, inhalation]P203, P260, P262, P264, P264+P265, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P305+P354+P338, P316, P317, P318, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement) |
|---|---|
| 規制情報 | Hazard Traits - Developmental ToxicityGenotoxicityReproductive ToxicityStatus: Active Update: 29-09-2010 https://echa.europa.eu/registration-dossier/-/registered-dossier/1277Colchicine: Does not have an individual approval but may be used under an appropriate group standardThe New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.) |
| その他の安全情報 | IMAP assessments - Acetamide, N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl)-, (S)-: Human health tier I assessment- Indoor Air: Colchicine can be released into indoor air as fine particles or liquid spray (aerosol). |
| 輸送ラベル（DOT） | Poison |
| 火災危険 | Stable. (EPA, 1998) |
| 火災の可能性 | Slight. |
| 健康有害性 | It 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 considerablyas little as 7 mg of colchicine has proved fatal. (EPA, 1998) |
| FDA 要件 | 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. |
| 反応性グループ | Amides and Imides |
| Explosion Hazards | - Upper and lower explosive (flammable) limits in air are not available for colchicine. |
| Special Reports | IPCSPoisons Information Monograph (PIM) 141: Colchicine. (October 1995). Available from, as of August 25, 2009:[http://www.inchem.org/documents/pims/pharm/colchic.htm] |
| Reactivity Profile | COLCHICINE darkens on exposure to light. Incompatible with strong oxidizing agents. Also incompatible with mineral acids (NTP, 1992). |
| Chemical Dangers | - When heated to decomposition, colchicine emits toxic fumes of carbon monoxide, carbon dioxide, and nitrogen oxides. |
| 消火 | For drugs, solid, n.o.s., avoid breathing dusts and fumes from burning material. Keep upwind. Wear boots, protective gloves, and goggles.- Colchicine is non-combustible. |
| 応急処置 | Warning: Effects may be delayed. Severe exposure may lead to death within 7-36 hours from respiratory failure or other complications. Caution is advised. |
| Firefighting Hazards | The agent /colchicine/ itself does not burn, but it may decompose upon heating to produce corrosive and/or toxic fumes. |
| 消火手順 | If a tank, rail car, or tank truck is involved in a fire, isolate it for 0.5 miles (800 m) in all directionsalso 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 disposaldo not scatter the material. Use water spray or fogdo 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 nozzlesif 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 more Fire Fighting Procedures (Complete) data for COLCHICINE (6 total), please visit the HSDB record page. |
| 清掃方法 | 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. |
| 非火災時の漏出対応 | Precautions for drugs, solid, n.o.s., include the following. Avoid breathing dusts, and fumes from burning materials. Keep upwind. Avoid bodily contact with the material. Wear full protective clothing. Wash away any material which may have contacted the body with copious amounts of water or soap and water. (EPA, 1998) |
| 処分方法 | 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. |
| Preventive 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. |
| Isolation and Evacuation | Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]: |
| Effects of Short Term Exposure | Information is inconclusive about the carcinogenicity, developmental toxicity, or reproductive toxicity from chronic or repeated exposure to colchicine. Effects of chronic exposure to colchicine are mainly known from its use as a drug in human medicine. In these circumstances gastrointestinal symptoms are likely to cause discontinuation of the use of the drug, long before any other symptoms develop. Bone marrow depression with a condition marked by fever and other symptoms (agranulocytosis), persistent decrease in the number of blood platelets (thrombocytopenia), reduced white blood cell count (leukopenia), and anemia characterized by defective function of the blood-forming organs (aplastic anemia) may occur with prolonged colchicine administration. Loss of body and scalp hair (alopecia), rashes, blister-like inflammation of the skin (vesicular dermatitis), degeneration of certain nerves (peripheral neuritis or neuropathy), a break down of muscle tissue at the cellular level (myopathy), the absences of urine excretion (anuria), kidney (renal) damage, blood in the urine (hematuria), and one case of patches of purplish discoloration of the skin and mucous membranes (purpura) have also been reported with prolonged administration of colchicine. |
| Protective Action Criteria (PAC) | 0.082 [mg/m3]0.90 [mg/m3]1.9 [mg/m3] |
| Personal Protective Equipment (PPE) | For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)First Responders should use a NIOSH-certified Chemical, Biological, Radiological, Nuclear (CBRN) Self Contained Breathing Apparatus (SCBA) with a Level A protective suit when entering an area with an unknown contaminant or when entering an area where the concentration of the contaminant is unknown. Level A protection should be used until monitoring results confirm the contaminant and the concentration of the contaminant. NOTE: Safe use of protective clothing and equipment requires specific skills developed through training and experience. [Table#4370]GENERAL INFORMATION |
| 体内負荷 | Colchicine is distributed into human milk. In a limited number of nursing women receiving long-term colchicine therapy at dosages of 1-1.5 mg daily, peak concentrations of the drug in milk were similar to serum concentrations and ranged from 1.9-8.6 ng/mL. Higher concentrations of the drug in milk (31, 24-27, or 10 ng/mL at 2, 4, or 7 hours, respectively, after a dose) have been reported in the absence of concurrent serum concentration data in a nursing woman receiving colchicine 1 mg daily. |
| 相互作用 | Colchicine has been shown to induce reversible malabsorption of vitamin B12, apparently by altering the function of ileal mucosa.Results of animal studies have suggested that colchicine may enhance response to sympathomimetic agents and CNS depressants.(1) Renal failure, either pre-existing or induced by a nephrotoxic drug, increases the risk of adverse effects in patients taking colchicine(2) Combining colchicines with a macrolide (except for spiramycin) carries a risk of life-threatening pancytopenia(3) Ciclosporin co-administration can aggravate the neuromuscular adverse effects of colchicine(4) Combining colchicine with lipid-lowering drugs (statins and fibrates) can cause myopathy(5) Several mechanisms have been implicated: competition for cytochrome P450 or P-glycoprotein, additive adverse effects (especially on muscle), and colchicine accumulation due to a reduction in its renal excretion(6) Patients with gout should use colchicine only after failure of symptomatic treatment: ice application, paracetamol, and possibly ibuprofen, a nonsteroidal antiinflammatory drug with well-documented adverse effects(7) If colchicine is nevertheless used, it should be at the minimum effective dose. Close clinical monitoring is required in order to detect early signs of adverse effects, especially diarrhea, the earliest sign in patients with renal failure and in the elderly.Colchicine and 3-hydroxy-3-methy-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are well known to cause myopathy. Myotoxicity is dose-dependent in both drugstherefore, the onset of symptoms usually takes months or years. We report the case of a patient with chronic renal failure who had been taking simvastatin for 2 years and developed acute weakness 2 weeks after the start of treatment with colchicines for recurrent gout. The electromyography and elevated muscle enzymes indicated that his symptoms were caused by myopathy. When this patient stopped taking both drugs, his weakness resolved rapidly. Acute myopathy induced by combination therapy with colchicines and simvastatin is rare. In patients with chronic renal failure, co-administration of colchicine with simvastatin may accelerate the onset of myopathy because CYP3A4 (part of cytochrome P450) is crucial in the breakdown of both drugs. When adding colchicine to a medication regimen that includes a HMG-CoA reductase inhibitor for patients with renal insufficiency, drugs that are metabolized outside the CYP3A4 system (e.g., fluvastatin and pravastatin) should be selected instead.For more Interactions (Complete) data for COLCHICINE (13 total), please visit the HSDB record page. |
| Hepatotoxicity | Chronic therapy with colchicine is uncommonly associated with serum aminotransferase or alkaline phosphatase elevations and has, indeed, been used off label as therapy of liver diseases, including alcoholic hepatitis and primary biliary cirrhosis. Despite decades of wide spread use, there have been no published cases of idiosyncratic liver disease attributed to colchicine use. Interestingly, liver biopsies done in patients receiving colchicine often show scattered mitotic figures in hepatocytes (ring mitoses) without accompanying liver cell injury. |
| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1,900(SRC), determined from a log Kow of 1.03(2) and a structure estimation method(3), indicates that colchicine is expected to have low mobility in soil(SRC). Volatilization of colchicine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.8X10-17 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Colchicine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2009).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1,900(SRC), determined from a log Kow of 1.03(2) and a structure estimation method(3), indicates that colchicine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 1.8X10-17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 2.2(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2009).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), colchicine, which has an estimated vapor pressure of 3.2X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase colchicine may be removed from the air by wet or dry deposition(SRC). Colchicine contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC). |
| 有害作用 | The most common adverse reactions are related to the gastrointestinal tract. Diarrhea is the most commonly reported symptom (23%), followed by vomiting (17%) and nausea (4% to 17%). Central nervous system symptoms, such as fatigue and headache, and endocrine and metabolic conditions, such as gout and pharyngolaryngeal pain, have been reported. |
| 暴露経路 | Colchicine can be absorbed into the body by ingestion, inhalation, or eye contact. Colchicine can also be injected through the skin or administered intravenously. It is unknown whether colchicine can be absorbed through intact skin.Colchicine is rapidly absorbed after oral administration, probably from the jejunum and ileum. However, the rate and extent of absorption are variable, depending on the tablet dissolution ratevariability in gastric emptying, intestinal motility, and pH at the absorption siteand the extent to which colchicine is bound to microtubules in gastrointestinal mucosal cells. |
| Milk Concentrations | EXPERIMENTAL: Colchicine is distributed into human milk. In a limited number of nursing women receiving long-term colchicine therapy at dosages of 1-1.5 mg daily, peak concentrations of the drug in milk were similar to serum concentrations and ranged from 1.9-8.6 ng/mL. Higher concentrations of the drug in milk (31, 24-27, or 10 ng/mL at 2, 4, or 7 hours, respectively, after a dose) have been reported in the absence of concurrent serum concentration data in a nursing woman receiving colchicine 1 mg daily. |
| 毒性の概要 | IDENTIFICATION: Colchicine is an antigout preparations. Colchicine is available as tablets and, in some countries, as injectable solutions. Colchicine is an alkaloid of Colchicum autumnale (autumn crocus, meadow saffron). Colchicum is also present in Gloriosa superba. Colchicine is a pale yellow odorless powder or scales. It darkens on exposure to light. Colchicine is used for acute gout attacks to reduce pain and inflammation. It may be used on long-term basis to prevent or reduce the frequency of attacks. Colchicine is used on long-term basis to prevent fever and recurrent polyserositis. Colchicine is effective in preventing the amyloidosis in this condition. Colchicine has been showed to be effective in the treatment of articular, cutaneous and mucosal symptoms. Colchicine has been used in the treatment of scleroderma and sarcoidosis. HUMAN EXPOSURE: Main risks and target organs: Colchicine exerts a multiorgan toxicity. The main toxic effects are related to the effects of colchicine on cellular division and account for diarrhea, bone marrow depression, alopecia. Other acute effects are hypovolemia, shock, and coagulation disturbances, which may lead to death. Summary of clinical effects: Toxic manifestations appear after a delay of 2 to 12 hours following ingestion or parenteral administration. Symptomatology progresses in three stages: Stage I (Day 1 to 3) gastrointestinal and circulatory phase: Severe gastrointestinal irritation: Nausea, vomiting, abdominal cramps, severe diarrhea. Dehydration, hypovolemia, shock. Cardiogenic shock may occur and may result in death within the first 72 hours. Hypoventilation, acute respiratory distress syndrome. Stage II (Day 3 to 10) bone marrow aplasia phase: Bone marrow aplasia with agranulocytosis. Coagulation disorders with diffuse hemorrhages. Rhabdomyolysis, polyneuritis, myopathy, acute renal failure and infections. Stage III: (After 10 day) recovery phase: Alopecia. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxications after parenteral administration are rare, however, the toxic dose appears to be lower than the oral toxic dose. A fatal bone marrow aplasia in a 70 year-old man after 10 mg intravenous colchicine over 5 days. Intoxication with multisystemic reactions after instillation of colchicine into the penile urethra for treatment of condyloma acuminata. Absorption by route of exposure: Oral: Rapidly absorbed from the gastro-intestinal tract. Peak plasma concentration is reached 0.5 to 2 hours after ingestion. Half time of absorption is 15 minutes. Absorption may be modified by pH, gastric contents, intestinal motility. Colchicine is not totally absorbed. There is an important hepatic first pass effect. Colchicine distributes in a space larger than that of the body. In severe renal or liver diseases the volume of distribution is smaller. Colchicine accumulates in kidney, liver, spleen, gastro-intestinal wall and leucocytes and is apparently excluded in heart, brain, skeletal muscle. Colchicine crosses the placenta and has also been found in maternal milk. Biological half-life by route of exposure: Parenteral: After a single 2 mg intravenous dose the average plasma half-life is 20 minutes. Plasma half-life is increased in severe renal disease (40 min) and decreased in severe hepatic disease (9 min). Oral: After oral administration plasma concentrations reach a peak within 0.5 to 2 hours and afterwards decrease rapidly within 2 hours. The plasma half-life is 60 minutes. Colchicine may remain in tissues for as long as 10 days. Metabolism: Colchicine undergoes some hepatic metabolism. Colchicine is partially deacetylated in the liver. Large amounts of colchicine and of its metabolites undergo enterohepatic circulation. This may explain the occurrence of a second plasma peak concentration observed 5 to 6 hours after ingestion. Elimination by route of exposure: Colchicine is excreted unchanged (10 to 20 percent) or as metabolites. Oral: Urinary excretion amount to 16 to 47% of an administered dose. 50 to 70% of colchicine is excreted unchanged and 30 to 50% as metabolites. 20% of the dose administered is excreted in urine in the first 24 hours and 27.5% in the first 48 hours. Colchicine is detected in urine up to 7 to 10 days after ingestion. Urinary excretion is increased in patients with impaired hepatic function. Bile: 10 to 25% of colchicine is excreted in the bile. Feces: Large amounts of the drug are excreted in the feces. Breast Milk: Colchicine may be eliminated in breast milk. Intravenous: Feces: After intravenous administration 10 to 56% is excreted in the feces within the first 48 hours. Breast Milk: Colchicine may be eliminated in breast milk. Mode of action: Colchicine binds to tubulin and this prevents its polymerization into microtubules. The binding is reversible and the half-life of the colchicine-tubulin complex is 36 hours. Colchicine impairs the different cellular functions of the microtubule: separation of chromosome pairs during mitosis (because colchicine arrests mitosis in metaphase), ameboid movements, phagocytosis. Mitosis blockade accounts for diarrhoea, bone marrow depression and alopecia. Colchicine may have a direct toxic effect on muscle, peripheral nervous system and liver. Inhibition of cellular function does not, however, account for all the organ failures seen in severe overdose. Pharmacodynamics: Gout inflammation is initiated by urate crystals within tissues. The crystals are ingested by neutrophils but this leads to the release of enzymes and the destruction of the cells. Chemotactic factors are released and attract more neutrophils. Colchicine may act by preventing phagocytosis, the release of chemotactic factors and the response of neutrophils. Colchicine has other properties such as antipyretic effects, respiratory depression, vasoconstriction and hypertension. Adults: Oral: The severity and the mortality rate of the poisoning is directly related to the dose ingested. Intravenous: A fatal bone marrow aplasia in a 70-year-old patient is reported. The enhanced toxicity of intravenous colchicine is probably due to the higher bioavailability of colchicine after parenteral administration. Teratogenicity: Colchicine is contraindicated in pregnancy as Down's syndrome and spontaneous abortion have been reported. Colchicine should be discontinued three months prior to conception. Interactions: A case of acute cyclosporin nephrotoxicity induced by colchicine administration has been reported. Colchicine may interfere with cyclosporin pharmacokinetics by increasing cyclosporin plasma levels either by enhancing cyclosporin absorption or by reducing its hepatic metabolism. Main adverse effects: Gastrointestinal symptoms are a common complication of chronic colchicine therapy. Fatal outcomes have been reported after intravenous colchicine therapy. Gastrointestinal: vomiting, diarrhoea, abdominal discomfort, paralytic ileus, malabsorption syndrome with steatorrhea. Hematological: Bone marrow depression with agranulocytosis, acute myelomonocytic leukaemia, multiple myeloma, thrombocytopenia. Neurological: Peripheral neuritis, myopathy and rhabdomyolysis. Dermatological: Allergic reactions are rare urticariaoedema may be seen. Alopecia has been reported after chronic treatment. Reproductive system: A reversible, complete azoospermia has been reported. Metabolic: Colchicine is capable of producing a reversible impairment of vitamin B12 absorption. Porphyria cutanea tarda has been reported. Others: Hyperglycemia has been reported in a 58-year-old woman who ingested colchicine and developed transient diabetes mellitus has been reported. Hyperlipemia: A transient hyperlipemia has been reported. Hyperuricemia: A transient hyperuricemia has also been noted. Hyperthermia-fever: Occurrence of fever may be relate to an infectious complication, especially during the stage of aplasia. Special risks: Pregnancy: Two cases of Down's syndrome babies have been reported. The obstetric histories of 36 women with familial Mediterranean fever on long-term colchicine treatment between 3 and 12 years have been reported. Seven of 28 pregnancies ended in miscarriage. Thirteen women had periods of infertility. All 16 infants born to mothers who had taken colchicine during pregnancy were healthy. The authors do not advise discontinuation of colchicine before planned pregnancy but recommend amniocentesis for karyotyping and reassurance. Breast-feeding: As colchicine is eliminated in the breast milk breast-feeding should be avoided.The precise dose of colchicine that results in significant toxicity is unknown. Toxicity can occur after ingesting a dose as low as 7 mg over 4 days, while other patients have survived after taking doses exceeding 60 mg. In one review involving 150 patients who experienced a colchicine overdose, ingesting doses exceeding 0.8 mg/kg resulted in death.Colchicine inhibits microtubule assembly in various cells, including leukocytes, probably by binding to and interfering with polymerization of the microtubule subunit tubulin. Although some studies have found that this action probably does not contribute significantly to colchicine's antigout action, a recent in vitro study has shown that it may be at least partially involved. |
| Signs and Symptoms | - Eye contact with liquid colchicine may produce clouding of the cornea that clears in a few weeks.- Gastrointestinal phase: Nausealoss of appetite (anorexia)abdominal painvomiting (emesis)profuse, watery, and bloody diarrheajoint paingeneralized weaknessfeverrashesand hypovolemic shock.- See Signs/Symptoms Ingestion Exposure.- . |
| Ongoing Test Status | The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of September 30, 2009: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=64-86-8] |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of colchicine can be estimated to be 1,900(SRC). According to a classification scheme(2), this estimated Koc value suggests that colchicine is expected to have low mobility in soil. |
| Natural Pollution Sources | Colchicine is an alkaloid of the meadow saffron, Colchicum autumnale. The plant has been used in the treatment of articular disorders since the sixth century(1).Colchicine, an alkaloid, is found in Colchicum autumnale (common names: Meadow Saffron, Autumn Crocus), as well as in Colchicum luteum, Merendera persica, Androcymbium gramineum,Gloriosa superba, Littonia modesta.From Colchicum autumnale by extraction and subsequent crystallization.COLCHICUM AUTUMNALE (MEADOW SAFFRON, AUTUMN CROCUS) IS LOCALLY ABUNDANT IN MEADOWS THROUGHOUT MOST OF EUROPE, & HAS BECOME NATURALIZED IN PARTS OF AMERICA. ALL PARTS OF /COLCHICUM AUTUMNALE/ ... CONTAIN THE ALKALOIDS COLCHICINE & COLCHICEINE, OF WHICH THE FORMER IS MORE TOXIC. BOTH ALKALOIDS WITHSTAND STORAGE, DRYING, AND BOILING. |
| CERCLA 報告数量 | Colchicine is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 10 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 micronsor is handled in solution or in molten formor meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... . |
| 水環境危害等級（WGK） | 3 |
| TSCA 収載状態 | TSCA listed |
| RTECS 番号 | GH0700000 |
| 輸送番号（UN） | UN 1544 6.1/PG 1 |
| 毒性 | LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson)in mice (mg/kg): 4.13 i.v. (Beliles) |
| 税関コード | 29399990 |
| 危険文句（R） | 26/28-41-46 |
| 危険表示 | T+,T,Xi |
| 安全措置（S） | 13-45-36/37/39-28-26-53 |
| 危険等級 | 6.1Acute Tox. 2 OralMuta. 1B |
| 包装等級 | I |
| 貯蔵分類 | 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials |
| 有害物質データ | 64-86-8(Hazardous Substances Data) |
用途
解説
C22H25NO6(399.44)．ユリ科イヌサフランColchicum autumnaleの種子に多く含まれている(約0.8％)，トロポロン核をもった中性アルカロイド．"黄色の結晶．融点155 ℃．[α]D "－121°(クロロホルム)．低濃度で植物の染色体倍加作用を有し，4倍体を得ることができるので貴重な薬品である．痛風発作の緩解や予防に有効であるが，中枢神経の麻ひ作用を有し，大量では呼吸麻ひによって死に至る．LD50 1.7 mg/kg(マウス，静注)．[CAS 64-86-8]森北出版「化学辞典（第2版）
用途
コルヒチン(colchicine)とはイヌサフラン科のイヌサフラン（Colchicum autumnale）の種子や球根に含まれるアルカロイドである。リウマチや痛風の治療に用いられてきたが、毒性も強く下痢や嘔吐などの副作用を伴う。また種なしスイカなどの倍数体植物種の作出にも用いられる。
用途
同調培養用試薬。
用途
チューブリンに特異的に結合 することによって、微小管形成阻害作用を示 します。
用途
チューブリンに特異的に結合 することによって、微小管形成阻害作用を示 します。
用途
コルヒチンは，アルカロイドの一種で、ユリ科のイヌサフラン（コルチカム）の種子や球茎に含まれる。分子式はC22H25NO6で、炭素の7員環をもった構造である。分裂中の植物細胞に作用して紡錘体の形成を阻害し、染色体の倍化をおこすので、細胞遺伝学の研究や育種に利用されている。種なしスイカなどの品種改良はその例である。医薬としては急性の痛風発作の特効的治療薬として知られる。発作の起り始め，とくに数時間以内に治療を開始すれば大部分の患者は激烈な痛みから救われる。しかしこの薬物は痛風以外の関節炎，関節リウマチなどには無効であり，また鎮痛作用も認められない, 長期連用により血液障害や脱毛、発疹(はっしん)、胃腸障害などの副作用がみられる。1錠中に0.5ミリグラム含有、1日3～4ミリグラムを6～8回に分けて服用する。［幸保文治・星川清親］
説明
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
来歴
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 successfullyColchicine 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).
使用
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.
一般的な説明
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.
製法・合成法
純化方法
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.]