Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
데스플루란
데스플루란 · Suprane · i653 · Desfluran · esflurane · DESFLURANE · DESFLURANE USP · Desflurane (0.5 mL)
식별자 및 물리적 특성
| CAS No. | 57041-67-5 |
|---|---|
| 분자식 | C3H2F6O |
| 평균 분자량 | 168.04 g/mol |
| 단동위원소 질량 | 168.000984 g/mol |
| SMILES | FC(F)OC(F)C(F)(F)F |
| InChIKey | DPYMFVXJLLWWEU-UHFFFAOYSA-N |
| PubChem CID | 42113 |
| ChEMBL | CHEMBL1200733 |
| ChEBI | CHEBI:4445 |
| EC No. | 688-023-8 |
| DTXSID | DTXSID80866606 |
| 현지명 | 데스플루란 |
화학 및 물리적 성질
| XLogP | 2.6 |
|---|---|
| 극성 표면적 | 9.2 |
| 수소 결합 공여자 수 | 0 |
| 수소 결합 수용자 수 | 7 |
| 회전 가능 결합 수 | 2 |
| 무거운 원자 수 | 10 |
| 형식 전하 | 0 |
| 복잡도 | 97.7 |
| 의약품 | Pharmaceuticals -> Nervous system -> AnestheticsPharmaceuticals -> Anesthetics |
| LogP(분배 계수) | 1.9 |
| 냄새 | Slight non-pungent odor |
| 밀도 | 1.44Relative density (water = 1): 1.51,47 g/cm3 |
| Color/Form | Liquid |
| 용해도 | Negligible3.54e+00 g/LSolubility in water: poor물에 거의 녹지 않으며 무수 에탄올과 섞입니다. |
| Human Drugs | Breast FeedingLactationAnesthetics, InhalationFDA approved drugs -> Active ingredient |
| 끓는 점 | 23.5 °C74.3 °F23-24°C |
| 증기 밀도 | 1.44 |
| 증기압 | 88.53 kPa at 20 °Capproximately 700 mm Hg at 22-23 °CVapor pressure, kPa at 20 °C: 89700 [email protected] °F |
| Physical Description | LiquidCOLOURLESS LIQUID.Colorless liquid. |
| Other Experimental Properties | VolatilePartition coefficient at 37 °C: (blood/gas): 0.424(saline/gas): 0.225(oil/gas): 18.7Hydroxyl radical reaction rate constant = 4.40X10-15 cu cm/molec-sec at 25 °C |
| 굴절률 | 1.3577 (estimate) |
| 물리적 상태 | 액체 |
| 색상 | 투명한 |
| 헨리 상수 | 1.4×10-4 mol/(m3Pa) at 25℃, HSDB (2015) |
| 주요 응용 | 의약품(소분자) |
| InChI | 1S/C3H2F6O/c4-1(3(7,8)9)10-2(5)6/h1-2H |
| InChIKey | DPYMFVXJLLWWEU-UHFFFAOYSA-N |
| SMILES | FC(F)(F)C(F)OC(F)F |
| EPA | Ethane, 2-(difluoromethoxy)-1,1,1,2-tetrafluoro-, (+-)- (57041-67-5) |
화학적 성질
Desflurane is a clear, colourless, mobile, heavy liquid. It is similar to isoflurane (CHF2-O-CHCl-CF3) in that both are halogenated compounds of methyl ethane, except that chlorine is replaced with fluorine in the α-ethyl portion. The halogenation of fluorine reduces the solubility of blood and tissues and alters the boiling point, vapor pressure and stability of desflurane, enhancing its molecular stability as well as its resistance to biodegradation and alkaline degradation.
안전 및 규제
| GHS 분류 | This chemical does not meet GHS hazard criteria for 20% (1 of 5) of reports.DangerH315 (40%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P260, P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 5 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 화재 위험 | Not combustible. Gives off irritating or toxic fumes (or gases) in a fire. |
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including desflurane, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Chemical Dangers | Decomposes on contact with hot surfaces or flames. This produces corrosive gases such as hydrogen fluoride. |
| Physical Dangers | The vapour is heavier than air and may accumulate in lowered spaces causing a deficiency of oxygen. |
| Hazard Classes and Categories | Skin Irrit. 2 (40%) |
| Critical Temperature and Pressure | Critical temperature: 376.46 Kcritical pressure: 2610.3 kPa |
| Hazardous Reactivities and Incompatibilities | No discernible degradation occurs in the presence of strong acids. Desflurane does not corrode stainless steel, brass, aluminum, anodized aluminum, nickel plated brass, copper, or beryllium.Desflurane is chemically stable. The only known degradation reaction is through prolonged direct contact with soda lime producing low levels of fluoroform (CHF3). The amount of CHF3 obtained is similar to that produced with MAC-equivalent doses of isoflurane. |
| 소화 | In case of fire in the surroundings, use appropriate extinguishing media. |
| 응급 조치 | Fresh air, rest. Artificial respiration may be needed. Refer for medical attention.Remove contaminated clothes. Rinse and then wash skin with water and soap.First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.Rinse mouth. Refer for medical attention . |
| 안전 보관 | Ventilation along the floor. |
| 소화 절차 | As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing. Move containers from fire area if you can do so without risk.Water fog, dry chemical, or carbon dioxide as appropriate for surrounding fire and materials. Do not use water jet as an extinguisher, as this will spread the fire. |
| 보관 조건 | Store at room temperature, 15 -30 °C (59-86 °F). SUPRANE (desflurane, USP) has been demonstrated to be stable for the period defined by the expiration dating on the label. The bottle cap should be replaced after each use of SUPRANE.Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. |
| 정리 방법 | Collect and reclaim or dispose in sealed containers at licensed waste disposal site. This product, in its present state, when discarded or disposed of, is not a hazardous waste according to Federal regulations (40 CFR 261.4 (b)(4)). Under RCRA, it is the responsibility of the user of the product to determine, at the time of disposal, whether the product meets RCRA criteria for hazardous waste. Dispose in accordance with all applicable regulations. |
| 처리 방법 | 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: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal. |
| 누출 처리 | Personal protection: self-contained breathing apparatus. Ventilation. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations. |
| Preventive Measures | As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Clean equipment and work surfaces with suitable detergent or solvent after use. After removing gloves, wash hands and other exposed skin thoroughly. |
| Eye Prevention | Wear safety spectacles or eye protection in combination with breathing protection. |
| Inhalation Risk | A harmful contamination of the air can be reached very quickly on evaporation of this substance at 20 °C. |
| Skin Prevention | Protective gloves. |
| Treatment | In the event of overdosage, or suspected overdosage, take the following actions: discontinue administration of Desflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function. (L1712) |
| 상호 작용 | Anesthetic concentrations of desflurane at equilibrium (administered for 15 or more minutes before testing) reduced the ED95 of succinylcholine by approximately 30% and that of atracurium and pancuronium by approximately 50% compared to N2O/opioid anesthesia. The effect of desflurane on duration of nondepolarizing neuromuscular blockade has not been studied.Benzodiazepines (midazolam 25-50 ug/kg) decrease the MAC of desflurane by 16% as do the opioids (fentanyl 3-6 ug/kg) by 50%.We investigated effects of vitamin C and E (VCE) administration on desflurane-induced oxidative toxicity and element changes in the blood of operative patients under desflurane general anesthesia. Forty American Society of Anesthesiologists I or II Physical Status adult patients were scheduled for elective surgery. The patients were randomly divided into two groups. Control and VCE group was introduced to anesthesia with desflurane. VCE was administreted to patients in the control and VCE group before 1 hour of anesthesia with desflurane. Baseline (preoperative) and postoperative (at the 1(st), the 24(th), and 72(th) hr), blood samples were taken from the first and second groups. Erythrocyte and plasma lipid peroxidation levels at the 1(st), 24(th), and 72(th) hours were higher in the control than in baseline group, although their levels at the same periods were lower in the VCE group than in the control. Vitamin E levels at the postoperative 1(st) and 24(th) hours and erythrocyte glutathione peroxidase (GSH-Px) activity at the postoperative 1(st), 24(th), and 72(th) hours was lower than in baseline values. Erythrocyte GSH-Px activity and plasma vitamins A, C, and E levels at the postoperative 1(st), 24(th), and 72(th) hours were higher in the VCE group than in the control group. Erythrocyte and plasma reduced glutathione, plasma ?-carotene, and serum copper, while zinc, selenium, aluminum, iron, magnesium, and calcium levels did not differ between preoperative and postoperative periods in both groups. In conclusion, VCE combination prevented the desflurane-induced vitamin E and GSH-Px consumptions to strengthen the antioxidant levels in the blood of operative patients. |
| 건강 영향 | It may cause tachycardia and airway irritability when administered at concentrations greater than 10 vol%. [Wikipedia] |
| Hepatotoxicity | Prospective, serial blood testing often demonstrates minor transient elevations in serum aminotransferase levels in the 1 to 2 weeks after major surgery and use of halogenated anesthetics. Appearance of ALT levels above 10 times the upper limit of normal, however, is distinctly unusual and points to significant hepatotoxicity. Clinically apparent, severe hepatic injury from desflurane is very rare, with only isolated case reports having been published and not all of which were very convincing. The injury is marked by acute elevations in serum aminotransferase levels (5- to 50-fold) and appearance of jaundice within 2 to 21 days of surgery. There are usually minimal increases in alkaline phosphatase and gammaglutamyl transpeptidase levels. Jaundice is usually preceded by a day or two of fever and may be accompanied by rash and eosinophilia. The acute liver injury may be self-limited and resolve within 4 to 8 weeks, but can be severe and associated with acute liver failure. A strong risk factor is previous exposure to any of the halogenated anesthetics and particularly a history of halothane hepatitis or unexplained fever and rash after anesthesia with one of these agents. The differential diagnosis of acute liver injury after surgery and anesthesia is often challenging, and a clinical picture similar to desflurane induced hepatitis can be caused by shock or ischemia, sepsis, acetaminophen overdose, acute viral or herpes hepatitis, as well as other idiosyncratic forms of drug induced liver injury. |
| 환경 거동 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 98(SRC), determined from a structure estimation method(2), indicates that desflurane is expected to have very high mobility in soil(SRC). Volatilization of desflurane from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.1X10-2 atm-cu m/mole(SRC), derived using a fragment constant estimation method(3). Desflurane is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 664 mm Hg at 20 °C(4). Biodegradation data in soil were not available(SRC, 2012).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 98(SRC), determined from a structure estimation method(2), indicates that desflurane is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 7.1X10-2 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 1.3 hours and 5 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 2.8(SRC), from an estimated log Kow of 2.8(6) 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, 2012).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), desflurane, which has a vapor pressure of 664 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase desflurane is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 5 years(SRC), calculated from its rate constant of 4.40X10-15 cu cm/molecule-sec at 25 °C(3). Desflurane does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| 유해 작용 | Desflurane, along with the other inhalational agents, sevoflurane and isoflurane, is a potent vasodilator and can cause a decrease in blood pressure by decreasing systemic vascular resistance. A concomitant increase in heart rate sometimes occurs. Cardiac output is typically preserved with the use of this agent. Desflurane dilates cerebral arteries and decreases the cerebral metabolic rate. |
| 노출 경로 | The substance can be absorbed into the body by inhalation of its vapour and by ingestion.Rapidly absorbed into the circulation via the lungs following inhalation. |
| 독성 요약 | Desflurane is the most likely inhaled anesthetic to result in CO production, compared with isoflurane and sevoflurane. The production of CO is by the degradation of desflurane by desiccated CO2 absorbent, barium hydroxide lime. The drug can produce clinically significant levels of CO, stressing the importance of replacing dried CO2 absorbents.Desflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Desflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Desflurane also binds to and agonizes the GABA receptor, the large conductance Ca<sup>2+</sup> activated potassium channel, the glycine receptors, and antagonizes the glutamate receptors. |
| Signs and Symptoms | Cough. Sore throat. Dizziness. Drowsiness. Headache. Unconsciousness.Dry skin. Redness.Redness. Pain.See Inhalation. |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of desflurane can be estimated to be 98(SRC). According to a classification scheme(2), this estimated Koc value suggests that desflurane is expected to have high mobility in soil. |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ We examined the potential toxicity of desflurane in 13 young 25.0 +/- 2.3 (mean +/- SD) yr-old men, given 7.35 +/- 0.81 MAC-hours of desflurane anesthesia. Hepatic and renal function tests, serum electrolytes, and standard urine and hematologic tests were performed before, during, and after anesthesia. No toxicity was found. There were no changes in tests of hepatocellular integrity (plasma alanine transferase activity), synthetic function (serum albumin, prothrombin time, partial thromboplastin time), or renal function (serum creatinine concentration, blood urea nitrogen concentration). Decreases in red blood cell count, hematocrit, and blood hemoglobin concentration during and immediately after anesthesia were attributed to blood sampling and infusion of intravenous electrolyte solution. These values returned by 4 days after anesthesia to values not different from those before anesthesia. Increased white blood cell counts and blood glucose concentrations noted during anesthesia with other inhaled anesthetics were also seen in these volunteers. Desflurane appears to have no greater toxicity than currently used inhaled anesthetics and, because of its lesser metabolism, may have lesser or not toxicity./HUMAN EXPOSURE STUDIES/ Eight patients receiving SUPRANE (desflurane, USP) were compared to six patients receiving isoflurane, all with chronic hepatic disease (viral hepatitis, alcoholic hepatitis, or cirrhosis). No differences in hematological or biochemical tests, including hepatic enzymes and hepatic function evaluation, were seen./HUMAN EXPOSURE STUDIES/ Nine patients receiving SUPRANE (desflurane, USP) (N=9) were compared to 9 patients receiving isoflurane, all with chronic renal insufficiency (serum creatinine 1.5-6.9 mg/dL). No differences in hematological or biochemical tests, including renal function evaluation, were seen between the two groups. Similarly, no differences were found in a comparison of patients receiving either SUPRANE (desflurane, USP) (N=28) or isoflurane (N=30) undergoing renal transplant./HUMAN EXPOSURE STUDIES/In an open-labelled clinical trial, the effect of desflurane anesthesia on liver function markers in pediatric patients was monitored. Fifty infants and children, 37 male, scheduled for elective cleft plate surgery were included in the study. Median age was 0.57 (0.25-5.45) years (range), mean desflurane exposure was 2.29 +/- 0.75 MAC-hr. Function markers were determined within 24 hr prior to and within 24-48 hr after anaesthesia. Complete data sets were available for total bilirubin 29, aspartate aminotransferase (ASAT) 36, alanine aminotransferase (ALAT) 35, and for alkaline phosphatase (AP) 28. Pre- and postanesthetic function tests were compared by means of Wilcoxon's matched-pairs test. Only for AP could a statistically significant reduction of the postanesthetic values be observed, while the other parameters showed no significant changes. Postanesthetic ASAT and ALAT were clearly reduced in three children who had unspecific highly elevated preanesthetic values. After the study, this observation could be repeated in at least one child, who received a further anesthesia with desflurane within 3 months. The data suggest that desflurane does not affect excretory or structural liver integrity in infants and children.For more Human Toxicity Excerpts (Complete) data for Desflurane (7 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Desflurane's production and use as an anaesthetic(1) may result in its release to the environment through various waste streams(SRC). |
| 수질 위해 등급(WGK) | WGK 3 |
| 관세 코드 | 2909191800 |
| 위험 표시 | Xi |
| 안전 문구(S) | 23 |
| 위험 등급 | GASEye Irrit. 2Repr. 2STOT SE 3 |
| 위험 참고 사항 | Irritant |
| 저장 분류 | 10 - Combustible liquids |
| 유해 물질 데이터 | 57041-67-5(Hazardous Substances Data) |
용도
개요
Desflurane is a new inhalation anesthetic introduced for induction and maintenance of general anesthesia in adults. Due to reports of respiratory irritation, desflurane may be used only for maintenance in children. Although almost structurally identical to isoflurane, a halogen replacement gives desflurane an improved pharmacokinetic profile. It is less soluble in blood and tissue and produces a fast onset of action and a more rapid recovery from anesthesia.
역사
Desflurane was first synthesized by Russel et al U.S. at the 29. of July 1975. The synthesis was started by using floural methyl hemiacetal (CF3CH(OH)OCH3) and converting it to 1,2,2,2- tetraflouroethyl methyl ether (CF3CHFOCH3). Next step was chlorinating two hydrogen atoms of the methyl-group to CF3CHFOCHCl2. This next to last molecule was charged with HF in the presence of antimony pentachloride (SBCL5) to Desflurane. But this way of synthesizing Desfluran was not usable for industrial synthesis, because of the less yield of Desflurane and the expensive educts.
용도
Anesthetic.
일반 설명
Desflurane is a nonflammable, colorless, very volatile liquidpackaged in amber-colored vials. The boiling point is22.8°C, and it requires a vaporizer specifically designed fordesflurane. The manufacturer states that the vials can bestored at room temperature. Desflurane has a blood:gas partitioncoefficient of 0.42, an MAC of 7.3% and an oil:gaspartition coefficient of 18.7. The low blood:gas partition coefficientleads to fast induction times and short recoverytimes. Desflurane is not recommended for induction anesthesiain children because of the high incidence of laryngospasms(50%), coughing (72%), breath holding (68%),and increase in secretions (21%). Desflurane can producea dose-dependent decrease in blood pressure and concentrationsexceeding 1 MAC may cause transient increases inheart rate. Desflurane can react with desiccated carbon dioxideabsorbents to produce carbon monoxide that may resultin elevated levels of carboxyhemoglobin.24.
제조 및 합성 방법
제조 방법
Isoflurane and bromine trifluoride were reacted overnight at room temperature to synthesize desflurane in 62% yield.