Doxorubicin

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

  H315：Verursacht Hautreizungen.

  H319：Verursacht schwere Augenreizung.

  H335：Kann die Atemwege reizen.

  H350：Kann Krebs verursachen.

  H362：Kann Säuglinge über die Muttermilch schädigen.

• Sicherheit

  P260：Dampf/Aerosol/Nebel nicht einatmen.

  P263：Kontakt während der Schwangerschaft /und der Stillzeit vermeiden.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

Adriamycin Chemische Eigenschaften,Einsatz,Produktion Methoden

• Chemische Eigenschaften

  Adriamycin is an orange to red cake-like or needle-like crystalline solid.

• Originator

  Adriblastina,Farmitalia,Italy,1971

• Verwenden

  Doxorubicin is one of the most effective neoplastic drugs, and is mainly used in combination with other drugs for treating solid tumors. This drug is used for leukemia, various sarcomas, practically every type of cancer, neuroblastomas, leukoses, and lymphomas.

• Verwenden

  Doxorubicin USP (Adriamycin) is used to traet soft-tissue and osteogenic sarcomas; Hodgkin’s disease; non-Hodgkin’s lymphomas; acute leukemia; cancer of thyroid, breast, lung, genitourinary (GU) tract; Wilm’s tumor; neuroblastoma.

• Verwenden

  Doxorubicin (adriamycin) is the most extensively studied of a family of highly fluorescent anthracycline antibiotics produced by several Streptomyces species, first reported in 1967 and later approved for human therapeutic use as an antitumour agent for the treatment of a wide range of cancers. Doxorubicin also exhibits anti-HIV and antibacterial activity. The mode of action of doxorubicin is thought to be due to intercalation of DNA and inhibition of nucleic acid synthesis.

• Indications

  Doxorubicin binds tightly to DNA by its ability to intercalate between base pairs and therefore is preferentially concentrated in nuclear structures. Intercalation results in steric hindrance, hence production of single-strand breaks in DNA and inhibition of DNA synthesis and DNA-dependent RNA synthesis. The enzyme topoisomerase II is thought to be involved in the generation of DNA strand breaks by the anthracyclines. Cells in S-phase are most sensitive to doxorubicin, although cytotoxicity also occurs in other phases of the cell cycle.

• Definition

  ChEBI: Doxorubicin is a deoxy hexoside, an anthracycline, an anthracycline antibiotic, an aminoglycoside, a member of tetracenequinones, a member of p-quinones, a primary alpha-hydroxy ketone and a tertiary alpha-hydroxy ketone. It has a role as an Escherichia coli metabolite. It is a conjugate base of a doxorubicin(1+). It derives from a hydride of a tetracene.

• Manufacturing Process

  Two 300 ml Erlenmeyer flasks, each containing 60 ml of the following culture medium for the vegetative phase, were prepared: peptone 0.6%; dry yeast 0.3%; hydrated calcium carbonate 0.2%; magnesium sulfate 0.01%; the pH after sterilization was 7.2. Sterilization has been effected by heating in autoclave to 120°C for 20 minutes. Each flask was inoculated with a quantity of mycelium of the mutant F.I.106 (the new strain thus obtained has been given the code F.I.106 of the Farmitalia microbiological collection and has been called Streptomycespeucetius var. caesius) corresponding to 1/9 of a suspension in sterile water of the mycelium of a 10 day old culture grown in a big test tube on the following medium: saccharose 2%; dry yeast 0.1%; bipotassium phosphate 0.2%; sodium nitrate 0.2%; magnesium sulfate 0.2%; agar 2%; tap water up to 100%. The flasks were then incubated at 28°C for 48 hours on a rotary shaker with a stroke of 30 mm at 220 rpm.，
  2 ml of a vegetative medium thus grown were used to inoculate 300 ml Erlenmeyer flasks with 60 ml of the following medium for the productive phase: glucose 6%; dry yeast 2.5%; sodium chloride 0.2%; bipotassium phosphate 0.1%; calcium carbonate 0.2%; magnesium sulfate 0.01%; ferrous sulfate 0.001%; zinc sulfate 0.001%; copper sulfate 0.001%; tap water to 100%. The glucose was previously sterilized separately at 110°C for 20 minutes. The resulting pH was 7. This was sterilized at 120°C for 20 minutes and incubated at 28°C under the same conditions by stirring, as for the vegetative media.
  The maximum concentration of the antibiotic was reached on the 6th day of fermentation. The quantity of adriamycin produced at this time corresponds to a concentration of 15 μg/ml.

• Trademarks

  Adriblastina (Farmitalia, Societa Farmaceutici Italia, Italy).

• Therapeutic Function

  Cancer chemotherapy

• Biologische Aktivität

  doxorubicin is a semi-synthesized anticancer agent derived from bacterial culture. [1] it is an anthracycline antibiotic. it is been widely used in blood cancers, solid tumors and sarcomas.doxorubicin intercalates into dna double strand and inhibits the progression of dna topoisomerase ii, stopping replication process. [2] doxorubicin also induces histone eviction from open chromatin, causing dna damage and epigenetic deregulation. [3]doxorubicin is administrated intravenously. approximately 75% of doxorubicin and its metabolites bind to plasma protein. doxorubicin does not cross blood brain barrier. 50% of the drug is eliminated unchanged from the body mainly though bile excretion. the remaining undergoes one-electron reduction, two-electron reduction, and deglycosidation. the major metabolite is a potent membrane ion pump inhibitor, which is associated with cardiomyopathy. [4]

• Mechanism of action

  Doxorubicin is not absorbed orally, and because of its ability to cause tissue necrosis must not be injected intramuscularly or subcutaneously. Distribution studies indicate rapid uptake in all tissues except the CNS. Extensive tissue binding, primarily intranuclear, accounts for the prolonged elimination half-life.The drug is extensively metabolized in the liver to hydroxylated and conjugated metabolites and to aglycones that are primarily excreted in the bile.

• Clinical Use

  Doxorubicin is one of the most effective agents used in the treatment of carcinomas of the breast, ovary, endometrium, bladder, and thyroid and in oat cell cancer of the lung. It is included in several combination regimens for diffuse lymphomas and Hodgkin’s disease. Doxorubicin can be used as an alternative to daunorubicin in acute leukemias and is useful in Ewing’s sarcoma, osteogenic sarcoma, soft-tissue sarcomas, and neuroblastoma. Some activity has been reported in non–oat cell lung cancer, multiple myeloma, and adenocarcinomas of the stomach, prostate, and testis.

• Nebenwirkungen

  The most important toxicities caused by doxorubicin involve the heart and bone marrow.Acutely, doxorubicin may cause transient cardiac arrhythmias and depression of myocardial function. Doxorubicin may cause radiation recall reactions, with flare-ups of dermatitis, stomatitis, or esophagitis that had been produced previously by radiation therapy. Less severe toxicities include phlebitis and sclerosis of veins used for injection, hyperpigmentation of nail beds and skin creases, and conjunctivitis. Because of its intense red color, doxorubicin will impart a reddish color to the urine for 1 or 2 days after administration.

• Sicherheitsprofil

  Confirmed carcinogen with experimental carcinogenic, neoplastigenic, and tumorigenic data. Poison by intraperitoneal, subcutaneous, parenteral, and intravenous routes. Human systemic effects by intravenous route: cardiac myopathy including infarction, nausea or vomiting, and effects on the hair. An experimental teratogen. Other experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits very toxic fumes of NO, and HCl

• mögliche Exposition

  An antibiotic product from streptomyces, used as anticancer drug

• Carcinogenicity

  Adriamycin is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.

• Versand/Shipping

  UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

• Inkompatibilitäten

  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

• Waste disposal

  It is inappropriate and possibly dangerous to the environment to dispose of expired or waste pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. 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.

• Einzelnachweise

  [1]brayfield, a, ed. (2013). doxorubicin. martindale: the complete drug reference. pharmaceutical press. retrieved 15 april 2014.
  [2]pommier y., et al. (2010). dna topoisomerases and their poisoning by anticancer and antibacterial drugs. chemistry & biology 17 (5): 421–433.
  [3]pang, b., et al. (2013). drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. nature communications 4 (5): 1908
  [4]boucek rj., et al. (1987). the major metabolite of doxorubicin is a potent inhibitor of membrane-associated ion pumps. a correlative study of cardiac muscle with isolated membrane fractions. j of biol chem 262: 15851-15856.

Adriamycin Upstream-Materialien And Downstream Produkte

Doxorubicin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(257)Suppliers

23214-92-8, Adriamycin Verwandte Suche: