6b-Glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one | 51372-29-3

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 肾上腺皮质激素类药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 6b-Glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one
• 英文别名: 11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-propyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one
• CAS: 51372-29-3；51333-22-3
• 化学式: C₂₅H₃₄O₆
• 分子量: 430.5
• InChiKey: VOVIALXJUBGFJZ-UHFFFAOYSA-N

物化性质

• 熔点：
  221-232°C (dec.)
• 比旋光度：
  D25 +98.9° (c = 0.28 in methylene chloride)
• 沸点：
  464.79°C (rough estimate)
• 密度：
  1.1046 (rough estimate)
• 溶解度：
  几乎不溶于水，易溶于二氯甲烷，微溶于乙醇（96%）。
• 颜色/状态：
  Crystals
• 蒸汽压力：
  8.81X10-15 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Chemical stability: Stable under recommended storage conditions.
• 旋光度：
  Specific optical rotation: +98.9 deg at 25 °C/D (c = 0.28 in methylene chloride)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

ADMET

代谢

布地奈德在肝脏中被细胞色素P-450（CYP）同工酶3A4代谢；两个主要代谢物与糖皮质激素受体的亲和力不到母化合物的1%。布地奈德以代谢物的形式通过尿液和粪便排出。

Budesonide is metabolized in the liver by the cytochrome P-450 (CYP) isoenzyme 3A4; the 2 main metabolites have less than 1% of affinity for glucocorticoid receptors than the parent compound. Budesonide is excreted in urine and feces as metabolites.

来源:Hazardous Substances Data Bank (HSDB)

代谢

哮喘是全球最常见的疾病之一，其主要治疗药物是吸入性糖皮质激素（GCs）。尽管这些药物被广泛使用，但大约30%的哮喘患者表现出一定程度的激素不敏感或对吸入性GCs无效。解释这种现象的一个假设是患者之间这些化合物清除率的差异。本研究的目的是确定CYP3A家族酶对GCs的代谢如何影响哮喘患者的疗效。在这项工作中，研究了四种经常处方的吸入性GCs，即曲安奈德醋酸酯、氟尼缩松、布地奈德和丙酸氟替卡松，通过CYP3A家族酶的代谢，以确定它们清除率的差异并识别它们的代谢物。观察到了代谢率和代谢命运的酶间和药物间的变异性。CYP3A4是所有化合物的最有效代谢催化剂，而CYP3A7的代谢速率最慢。CYP3A5，特别是在肺部GC代谢中特别相关，也被证明有效地代谢曲安奈德醋酸酯、布地奈德和丙酸氟替卡松。相比之下，氟尼缩松仅通过CYP3A4代谢，CYP3A5或CYP3A7没有显著转化。常见的代谢物包括6 Beta-羟基化和Delta (6)-脱氢化，适用于曲安奈德醋酸酯、布地奈德和氟尼缩松。通过NMR分析明确确立了Delta (6)-氟尼缩松的结构。代谢也发生在D环取代基上，包括曲安奈德醋酸酯和氟尼缩松的21-羧基代谢物。通过液相色谱-质谱和NMR分析还鉴定出了新型代谢物21-去甲曲安奈德醋酸酯。

Asthma is one of the most prevalent diseases in the world, for which the mainstay treatment has been inhaled glucocorticoids (GCs). Despite the widespread use of these drugs, approximately 30% of asthma sufferers exhibit some degree of steroid insensitivity or are refractory to inhaled GCs. One hypothesis to explain this phenomenon is interpatient variability in the clearance of these compounds. The objective of this research is to determine how metabolism of GCs by the CYP3A family of enzymes could affect their effectiveness in asthmatic patients. In this work, the metabolism of four frequently prescribed inhaled GCs, triamcinolone acetonide, flunisolide, budesonide, and fluticasone propionate, by the CYP3A family of enzymes was studied to identify differences in their rates of clearance and to identify their metabolites. Both interenzyme and interdrug variability in rates of metabolism and metabolic fate were observed. CYP3A4 was the most efficient metabolic catalyst for all the compounds, and CYP3A7 had the slowest rates. CYP3A5, which is particularly relevant to GC metabolism in the lungs, was also shown to efficiently metabolize triamcinolone acetonide, budesonide, and fluticasone propionate. In contrast, flunisolide was only metabolized via CYP3A4, with no significant turnover by CYP3A5 or CYP3A7. Common metabolites included 6 Beta-hydroxylation and Delta (6)-dehydrogenation for triamcinolone acetonide, budesonide, and flunisolide. The structure of Delta (6)-flunisolide was unambiguously established by NMR analysis. Metabolism also occurred on the D-ring substituents, including the 21-carboxy metabolites for triamcinolone acetonide and flunisolide. The novel metabolite 21-nortriamcinolone acetonide was also identified by liquid chromatography-mass spectrometry and NMR analysis.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：布地奈德（商品名：Rhinocort，MMX）是一种处方药，用于治疗过敏性鼻炎（Rhinocort鼻喷剂）和轻度至中度克罗恩病（MMX，肠溶胶囊）。人类暴露和毒性：贴片测试表明布地奈德可能导致迟发型过敏反应和特应性皮炎。在吸入暴露的情况下，报告了周围性皮炎。在口服给药的情况下，报告了白色念珠菌食管炎、吞咽困难、血压升高、下肢水肿和体重增加，尽管其中一些不良事件可能是与伏立康唑药物相互作用的结果。流行病学研究发现，吸入布地奈德与肺炎、心脏节律失常、白内障和骨折的风险增加有关。额外的流行病学研究发现，怀孕期间吸入布地奈德可能是后代内分泌和代谢紊乱的危险因素。还报告了低出生体重。在接受布地奈德治疗持续性哮喘的儿童中，也观察到了生长速度减慢、体重增长缓慢和骨骼成熟缓慢。在鼻腔布地奈德治疗期间，报告了鼻和喉咙的局部念珠菌感染。患者可能增加某些感染的风险，如水痘。在儿童和青少年中，布地奈德给药可能导致生长抑制。它还可能引起急性或迟发型超敏反应。在母亲怀孕期间接受皮质类固醇治疗的婴儿中，可能会出现低肾上腺皮质功能。动物研究：在致癌性研究中，口服布地奈德的大鼠中观察到了肝细胞肿瘤和神经胶质瘤。在皮下接受布地奈德的雌性大鼠中，观察到了怀孕和哺乳期间胚胎存活率和幼崽存活率的降低。在接受口服布地奈德的小鼠中检测到了幽门玻璃样变。

IDENTIFICATION AND USE: Budesonide (trade names: Rhinocort, MMX) is a prescription medication approved for the treatment of allergic rhinitis (Rhinocort nasal spray) and mild to moderate Crohn's disease (MMX, enteric coated capsules). HUMAN EXPOSURE AND TOXICITY: Patch tests have indicated that budesonide can produce delayed allergic reactions, and atopic dermatitis. In cases of inhalational exposure, periorificial dermatitis has been reported. In cases of oral administration, Candida albicans esophagitis, dysphagia, elevated blood pressure, lower extremity edema, and weight gain have been reported, although some of these adverse events may have been the result of a drug interaction with voriconazole. Epidemiological studies have found an increased risk of pneumonia, cardiac dysrhythmias, cataracts, and fractures associated with inhaled budesonide use. Additional epidemiological studies have found that budesonide inhalation during pregnancy may be a risk factor for offspring endocrine and metabolic disturbances. Low birth weight has also been reported. In children taking budesonide for persistent asthma, slower linear growth, slow weight gain, and slow skeletal maturation have also been observed. Localized Candidal infections of the nose and pharynx has been reported during intranasal budesonide therapy. Patients may be at an increased risk for certain infections, such as Varicella (chickenpox). In children and adolescents, administration of budesonide may cause growth suppression. It may also cause acute or delayed hypersensitivity reactions. Hypoadrenalism may occur in infants of mothers receiving corticosteroid therapy during pregnancy. ANIMAL STUDIES: In carcinogenicity studies, hepatocellular tumors and gliomas have been observed in rats that received oral budesonide. In female rats that received budesonide subcutaneously, a decrease in prenatal viability and viability of pups during pregnancy and lactation was observed. Pyloric hyalinization was detected in mice that received budesonide orally.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

长期使用布地奈德治疗并未与血清酶水平升高有关联，在临床试验中，与安慰剂治疗相比，丙氨酸氨基转移酶（ALT）升高的比率相似。在控制性试验中，没有报告与使用布地奈德有关的临床明显肝损伤的案例。与传统的系统性给药皮质类固醇不同，布地奈德并未与乙型肝炎再激活的发作有关。布地奈德已用于严重的自身免疫性肝病，没有证据表明它会加剧本已存在的肝损伤。由于它能够改善自身免疫性肝炎患者血清转氨酶的升高，因此停药后可能会出现反弹性升高，这也发生在传统皮质类固醇治疗中。此外，曾有个别案例报告布地奈德治疗期间出现急性血清转氨酶升高，但在停药后缓解，但相关记录有限，且患者同时使用了多种其他可能对肝脏有毒性的药物。

Long term therapy with budesonide has not been linked to elevations in serum enzyme levels, and in clinical trials rates of ALT elevations were similar with budesonide as with placebo treatment. In controlled trials, there were no reported cases of clinically apparent liver injury associated with its use. Unlike conventional systemically administered corticosteroids, budesonide has not been linked to episodes of reactivation of hepatitis B. Budesonide has been used in severe autoimmune liver diseases without evidence that it causes worsening of liver injury. Because it can improve serum aminotransferase elevations in patients with autoimmune hepatitis, its withdrawal may be followed by rebound elevations as also occurs with conventional corticosteroid therapy. In addition, there has been a single case report of acute serum aminotransferase elevations during budesonide therapy that resolved when the drug was stopped, but documentation was limited and the patient was on multiple other potentially hepatotoxic drugs.

来源:LiverTox

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：吸入的布地奈德进入母乳的量非常微小，婴儿的暴露量可以忽略不计。口服布地奈德大约只有9%的生物利用度；对于任何进入母乳的布地奈德，婴儿的生物利用度可能同样很低。专家意见认为，在哺乳期间可以使用吸入、鼻腔和口服皮质类固醇。 ◉ 对哺乳婴儿的影响：目前尚未有关于任何皮质类固醇的报告。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:The amounts of inhaled budesonide excreted into breastmilk are minute and infant exposure is negligible. When taken by mouth, budesonide is only about 9% bioavailable; bioavailability in the infant is likely to be similarly low for any budesonide that enters the breastmilk. Expert opinion considers inhaled, nasal and oral corticosteroids acceptable to use during breastfeeding. ◉ Effects in Breastfed Infants:None reported with any corticosteroid. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

口服糖皮质激素的类固醇精神症已经被很好地描述，然而，我们在文献搜索中并没有发现吸入糖皮质激素和长效β2受体激动剂联合使用与精神错乱有关联。我们描述了一位老年男性在使用布地奈德/福莫特罗（一种吸入型糖皮质激素和支气管扩张剂的组合）治疗慢性阻塞性肺病后一周内出现精神错乱的情况。停止使用组合吸入剂后，症状得到解决。几周后，患者再次住院并重新开始使用组合吸入剂。患者入院时神志清醒，定向正常，然而，在住院期间，他的混乱和幻觉症状逐渐加重。停止使用组合吸入剂后，他的混乱和幻觉症状在出院时得到了解决。这些事件的时间关系以及可能的Naranjo关联使得有合理的假设认为使用布地奈德/福莫特罗组合吸入剂导致了或促成了这位老年患者精神错乱的发生。精神错乱的发作可能是由于糖皮质激素从肺部沉积后的系统性吸收，在一个具有多种精神错乱风险因素的个体中复杂化。卫生保健提供者在给有精神错乱风险的老年患者开吸入型药物时，应该意识到这种潜在的药物不良反应。

Steroid psychosis has been well described with oral glucocorticoids, however, our search of the literature did not identify an association between delirium and the combination of inhaled glucocorticoids and long-acting beta-agonists. We describe the occurrence of delirium with the combination of an inhaled glucocorticoid and bronchodilator. An elderly male described confusion and hallucinations within 1 week after initiation of budesonide/formoterol for chronic obstructive pulmonary disease. The combination inhaler was discontinued with resolution of symptoms. Several weeks later, the patient was hospitalized and restarted on the combination inhaler. The patient was alert and oriented on admission, however, confusion and hallucinations progressed throughout his hospital stay. The combination inhaler was discontinued and his confusion and hallucinations resolved by discharge. The temporal relationship of these events and a probable Naranjo association allows for reasonable assumption that the use of the budesonide/formoterol combination inhaler caused or contributed to the occurrences of delirium in this elderly patient. The onset of delirium was likely due to the systemic absorption of the glucocorticoid from lung deposition, complicated in an individual with several predisposing risk factors for delirium. Health care providers should be aware of this potential adverse drug reaction when prescribing inhaled medications to older patients at risk for delirium.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

一位48岁的艾滋病毒感染女性在服用利托那韦增强的达芦那韦期间出现了库欣综合症特征。由于利托那韦和布地奈德的药物相互作用，确诊为库欣综合症。对于正在接受利托那韦增强的蛋白酶抑制剂（PIs）的艾滋病毒阳性患者，诊断医源性库欣综合症在临床上是一个挑战，因为与利托那韦增强的PIs相关的脂肪增生的临床特征相似。尽管这种并发症在使用吸入性氟替卡松时已经被广泛描述，但与治疗剂量吸入性布地奈德的相互作用并没有被广泛认识。

A 48-year-old woman with HIV infection developed Cushingoid features while she was taking ritonavir-boosted darunavir. Cushing's syndrome was confirmed due to the drug interaction between ritonavir and budesonide. Diagnosis of iatrogenic Cushing's syndrome in HIV-positive patients who are on ritonavir-boosted protease inhibitors (PIs) presents a clinical challenge due to similar clinical features of lipohypertrophy related to ritonavir-boosted PIs. Although this complication has been widely described with the use of inhaled fluticasone, the interaction with inhaled budesonide at therapeutic dose is not widely recognized.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

/MILK/ 不清楚布地奈德是否分布在于牛奶中。

/MILK/ Not known whether budesonide is distributed in milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当布地奈德通过鼻腔给药时，大约34%的剂量会进入全身循环。布地奈德的平均血浆峰浓度在大约0.7小时后达到。

When budesonide is administered intranasally, approximately 34% of a dose reaches systemic circulation. Mean peak plasma budesonide concentrations are achieved in about 0.7 hours.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

吸入性皮质类固醇（ICS）是治疗哮喘和慢性阻塞性肺病的主要治疗方法。然而，高度亲脂性的ICS在系统性组织中积累，可能导致不良反应。一种新型的高度亲脂性ICS，环索奈德及其活性代谢物（脱-CIC）的积累尚未见报道。在这里，我们比较了在小鼠中每天一次治疗14天后，脱-CIC和中等亲脂性的ICS，布地奈德（BUD）的组织积累情况。将[(3) H]-脱-CIC或[(3) H]-BUD单次、三次或14次每日剂量皮下给予雄性CD1白化小鼠，并在最后一次给药后4小时、24小时或5天处死。通过定量全身自动放射性显像研究放射性物质在组织中的分布。在单次给药以及重复给药后，两种皮质类固醇在大多数组织中的放射性分布模式相似。然而，脱-CIC和BUD之间的组织放射性浓度不同。单次给药后，两种皮质类固醇在大多数组织中的放射性浓度较低，但在每日给药14天后增加。在第14次给药后24小时和5天的脱-CIC组织放射性是BUD的大多数组织的2-3倍。作为第14次与第3次给药后5天的组织放射性浓度评估，脱-CIC的平均比率为5.2，BUD为2.7（p < 0.0001）。总之，脱-CIC的积累显著高于BUD。系统性积累可能导致长期治疗中不良反应的风险增加。

Inhaled corticosteroids (ICS) are mainstay treatment of asthma and chronic obstructive pulmonary disease. However, highly lipophilic ICS accumulate in systemic tissues, which may lead to adverse systemic effects. The accumulation of a new, highly lipophilic ICS, ciclesonide and its active metabolite (des-CIC) has not yet been reported. Here, we have compared tissue accumulation of des-CIC and an ICS of a moderate lipophilicity, budesonide (BUD), after 14 days of once-daily treatment in mice. Single, three or 14 daily doses of [(3) H]-des-CIC or [(3) H]-BUD were administered subcutaneously to male CD1 albino mice, which were killed at 4 hrs, 24 hrs or 5 days after the last dose. Distribution of tissue concentration of radioactivity was studied by quantitative whole-body autoradiography. Pattern of radioactivity distribution across most tissues was similar for both corticosteroids after a single as well as after repeated dosing. However, tissue concentration of radioactivity differed between des-CIC and BUD. After a single dose, concentrations of radioactivity for both corticosteroids were low for most tissues but increased over 14 days of daily dosing. The tissue radioactivity of des-CIC at 24 hrs and 5 days after the 14th dose was 2-3 times higher than that of BUD in majority of tissues. Tissue accumulation, assessed as concentration of tissue radioactivity 5 days after the 14th versus 3rd dose, showed an average ratio of 5.2 for des-CIC and 2.7 for BUD (p < 0.0001). In conclusion, des-CIC accumulated significantly more than BUD. Systemic accumulation may lead to increased risk of adverse systemic side effects during long-term therapy.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险类别码：
  R40
• 海关编码：
  2914509090
• 储存条件：
  -20°C 冰箱

SDS

---

Section 1. Chemical Product and Company Identification
Budesonide Catalog
YY448, YY1420, B1581,
Common Name/
Number(s).
Trade Name
51333-22-3
CAS#
Manufacturer
Commercial Name(s)
Synonym
Budesonide

---

Section 4. First Aid Measures
Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least
Eye Contact
15 minutes. Get medical attention.
In case of contact, immediately flush skin with plenty of water. Cover the irritated skin with an emollient. Remove
Skin Contact
contaminated clothing and shoes. Wash clothing before reuse. Thoroughly clean shoes before reuse. Get medical
attention.
Serious Skin Contact Wash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek medical attention.
Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious Inhalation Not available.
Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an
Ingestion
unconscious person. Loosen tight clothing such as a collar, tie, belt or waistband. Get medical attention if symptoms
appear.
Serious Ingestion Not available.

---

Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Not available.
Flash Points
Not available.
Flammable Limits
These products are carbon oxides (CO, CO2).
Products of Combustion
Fire Hazards in Presence of Slightly flammable to flammable in presence of heat.
Various Substances
Risks of explosion of the product in presence of mechanical impact: Not available.
Explosion Hazards in
Risks of explosion of the product in presence of static discharge: Not available.
Presence of Various
Substances
SMALL FIRE: Use DRY chemical powder.
Fire Fighting Media
LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
and Instructions
Not available.
Special Remarks on
Fire Hazards
Not available.
Special Remarks on
Explosion Hazards

---

Section 6. Accidental Release Measures
Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading
Small Spill
water on the contaminated surface and dispose of according to local and regional authority requirements.
Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on
Large Spill
the contaminated surface and allow to evacuate through the sanitary system.
Budesonide

---

Section 7. Handling and Storage
Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not
Precautions
ingest. Do not breathe dust. Wear suitable protective clothing. If ingested, seek medical advice immediately and
show the container or the label. Avoid contact with skin and eyes.
Keep container tightly closed. Keep container in a cool, well-ventilated area.
Storage

---

Section 8. Exposure Controls/Personal Protection
Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
Engineering Controls
recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal Protection Splash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used to
avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE
of a Large Spill
handling this product.
Not available.
Exposure Limits

---

Section 9. Physical and Chemical Properties
Solid. Odorless.
Physical state and O dor
appearance
Not available.
Taste
430.59 g/mole
Molecular Weight
White. Off-white.
Color
Not applicable.
pH (1% soln/water)
Not available.
Boiling Point
226.5°C (439.7°F)
Melting Point
Not available.
Critical Temperature
Not available.
Specific Gravity
Not applicable.
Vapor Pressure
Not available.
Vapor Density
Not available.
Volatility
Not available.
Odor Threshold
Not available.
Water/Oil Dist. Coeff.
Not available.
Ionicity (in Water)
Not available.
Dispersion Properties
Insoluble in cold water.
Solubility
Practically insoluble in Heptane.
Sparingly soluble in Ethanol.
Freely soluble in Chloroform.

---

Section 10. Stability and Reactivity Data
The product is stable.
Stability
Not available.
Instability Temperature
Conditions of Instability Excess heat
Incompatibility with various Not available.
substances
Budesonide
Non-corrosive in presence of glass.
Corrosivity
Not available.
Special Remarks on
Reactivity
Not available.
Special Remarks on
Corrosivity
Will not occur.
Polymerization

---

Section 11. Toxicological Information
Inhalation. Ingestion.
Routes of Entry
Toxicity to Animals Acute oral toxicity (LD50): >3200 mg/kg [Rat].
Chronic Effects on Humans Not available.
Hazardous in case of skin contact (irritant).
Other Toxic Effects on
Humans Slightly hazardous in case of ingestion, of inhalation.
Not available.
Special Remarks on
Toxicity to Animals
May cause adverse reproductive effects and birth defects (teratogenic)
Special Remarks on
Chronic Effects on Humans
Potential Health Effects:
Special Remarks on other
Skin: Causes skin irritation.
Toxic Effects on Humans
Eyes: Causes eye irritation.
Inhalation: May cause respiratory tract irritation.
Ingestion: May cause nausea, vomiting, headache, increased thirst/dry mouth, swollen or moon face, swollen ankels,
skin striae or markings, acne, respiratory infection. May also affect behavior/central nervous system (Central nervous
system depression, confusion, excitement, restlessness, a false sense of well-being, severe mood swings, unusual
tiredness or weakness, dizzienss, drowsiness, nervousness or difficulty sleeping), cardiovascular system (irregular
heartbeat, chest pain, high blood pressure). May also cause pain in the hips, knees, back, ribs, arms, shoulders, legs,
muscle cramps, numbness or tingling in fingers, toes, or other areas, eye pain, decreased or blurred vision, fever, sore
throat, sneezing, cough, or other signs of infection, wounds that won't heal, frequent urination, unusual bruising,
increased growth of hair on face or body, weight gain or loss
Medical Conditions Aggravated by Exposure: Tuberculosis; hypertension; heart problems; diabetes; osteoporosis;
glaucoma; cataracts; chronic liver disease; chicken pox or measles; Cushing's Syndrome; stomach or intestinal
disease, inclulding colitis; allergic reaction to Budesonide; pregnancy.

---

Section 12. Ecological Information
Not available.
Ecotoxicity
Not available.
BOD5 and COD
Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
The product itself and its products of degradation are not toxic.
Toxicity of the Products
of Biodegradation
Not available.
Special Remarks on the
Products of Biodegradation
Budesonide

---

Section 13. Disposal Considerations
Waste must be disposed of in accordance with federal, state and local environmental control
Waste Disposal
regulations.

---

Section 14. Transport Information
Not a DOT controlled material (United States).
DO T Cl assi fi cati on
Not applicable.
Identification
Not applicable.
Special Provisions for
Transport
DO T (Pi ctograms)

---

Section 15. Other Regulatory Information and Pictograms
No products were found.
Federal and State
Regulations
California prop. 65: This product contains the following ingredients for which the State of California has found to
California
cause cancer which would require a warning under the statute: No products were found.
Proposition 65
Warnings
California prop. 65: This product contains the following ingredients for which the State of California has found to
cause birth defects which would require a warning under the statute: No products were found.
Other Regulations EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances (EINECS no.
257-139-7)
Canada: Not listed on Canadian Domestic Substance List (DSL) or Canadian Non- Domestic Substance List (NDSL).
China: Not listed on National Inventory.
Japan: Not listed on National Inventory (ENCS).
Korea: Not listed on National Inventory (KECI).
Philippines: Not listed on National Inventory (PICCS).
Australia: Not listed on AICS.
WHMIS (Canada) CLASS D-2A: Material causing other toxic effects (VERY TOXIC).
Other Classifications
Class D-2B: Material causing other toxic effects (TOXIC).
R36/38- Irritating to eyes and skin. S26- In case of contact with eyes, rinse
DSCL (EEC)
immediately with plenty of water and seek
medical advice.
S37- Wear suitable gloves.
Health Hazard
HMIS (U.S.A.) 2 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
2 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
Budesonide
TDG(Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or equivalent.
Wear appropriate respirator when ventilation
is inadequate.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

布地奈德是一种糖皮质激素类药物，用于治疗哮喘和非传染性鼻炎。它通过抑制炎症反应和免疫反应来减轻症状。

作用机制

• 靶点: 主要是糖皮质激素受体。
• 生物活性:
  • 在人支气管上皮细胞系BEAS-2B和原代人支气管上皮细胞中，布地奈德有效地抑制eotaxin和RANTES蛋白质的产生。
  • 减少趋化因子和MCP-4的mRNA的衰变。
  • 抑制VEGF的分泌和VEGF mRNA表达。

体内研究

在大鼠实验中，布地奈德可以完全抑制LPS诱导产生的TNF-α、白细胞介素（IL）1beta、IL-6和单核细胞趋化蛋白（MCP）-1。此外，在A/J小鼠中，它还发挥化学预防作用。

临床应用

• 哮喘: 布地奈德气雾剂可用于轻症支气管哮喘。
• 非传染性鼻炎：适用于治疗这类病症。

注意事项与禁忌

• 慎用于肺结核、气道真菌感染或病毒感染患者。
• 孕妇应避免使用。
• 对依赖口服激素的病人，应在并用本品10天后逐渐减少口服激素剂量。

安全性

虽然布地奈德对大多数患者的副作用较小，但仍需注意其可能引起的咽痛、白色念珠菌感染等问题。此外，在严重应激状态或痰液变稠导致气道堵塞时，建议补充使用其他治疗方法如较大剂量水溶性皮质激素等。

急性毒性

• 腹腔 - 大鼠：LD50 (半数致死剂量) 为138毫克/公斤。
• 口服 - 小鼠：LD50 为4750毫克/公斤。

火灾危险与灭火方法

布地奈德在热分解过程中可能会排出有毒的辛辣刺激性烟雾。因此，在储存和运输时需要库房通风、低温干燥，并配备适当的消防设备如水、干粉、二氧化碳等灭火剂。

综上所述，布地奈德是一种有效的治疗哮喘和非传染性鼻炎的药物，但需注意其使用条件与潜在副作用。

反应信息

• 作为产物：
  描述：

  21-乙酰氧基-11beta-羟基-16alpha,17alpha-丙基甲基烯二氧代孕甾烷-1,4-二烯-3,20-二酮 以83.1的产率得到6b-Glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one
  参考文献：
  名称：

  一种布地奈德的制备方法

  摘要：

  本发明公开一种布地奈德的制备方法。泼尼松Ⅰ和醋酐Ⅱ反应生成17,21‑二乙酰氧基‑1,4‑孕甾二烯‑3,11,20‑三酮Ⅲ，Ⅲ于无水溶剂中脱酯得21‑乙酰氧基‑1,4,16‑孕甾三烯‑3,11,20‑三酮Ⅳ，Ⅳ氧化得16α,17α‑二羟基‑21‑乙酰氧基‑1,4‑孕甾二烯‑3,11,20‑三酮Ⅴ，Ⅴ和正丁醛Ⅵ缩合得16α,17α‑22(R,S)丙基亚甲基二氧‑21‑乙酰氧基‑1,4‑孕甾二烯‑3,11,20‑三酮Ⅶ，Ⅶ还原得16α,17α‑22(R,S)丙基亚甲基二氧‑11β‑羟基‑21‑乙酰氧基‑1,4‑孕甾二烯‑3,20‑二酮Ⅷ，Ⅷ碱催化得布地奈德Ⅸ。本发明方法适合工业化生产。

  公开号：

  CN105061549B

文献信息

• [EN] BUDESONIDE 21-PHOSPHATE SALTS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME<br/>[FR] SELS DE BUDÉSONIDE 21-PHOSPHATE ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：GENETIC S P A

  公开号：WO2021191366A1

  公开（公告）日：2021-09-30

  The present invention relates to salts of budesonide 21-phosphate with β2 adrenergic agonists, preferably with formoterol, pharmaceutical compositions containing the same and the use thereof in the treatment of respiratory inflammatory pathologies, obstructive pathologies and allergen-induced airway dysfunctions. The invention further relates to the process for preparing said salts.

  本发明涉及布地奈德21-磷酸盐与β2肾上腺素激动剂的盐，优选与福莫特罗合用，以及含有它们的制药组合物，并且在治疗呼吸道炎症病理、阻塞性病理和过敏原引起的气道功能障碍方面的应用。本发明还涉及制备上述盐的过程。
• [EN] NOVEL PROCESS FOR PREPARATION OF GLUCOCORTICOID STEROIDS<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE STÉROÏDES DE TYPE GLUCOCORTICOÏDE
  申请人：CORAL DRUGS PVT LTD

  公开号：WO2016120891A1

  公开（公告）日：2016-08-04

  The present invention discloses a process for the preparation of 16, 17-acetals of pregnane derivatives having formula (I) wherein each substituent is independently selected from; R1 is H or CH3; R2 is C1-C6 linear or branched alkyl, alkynyl group or cycloalkyl group; aryl or heteroaryl group; or R1 and R2 combine to form saturated, unsaturated C3-C6 cyclic or heterocyclic ring; R3 and R4 are same or different and each independently represents H or halogen; R5 is -OH or –OCOR wherein R represents H or C1-C6 linear, branched or cyclic alkyl group that may be substituted.

  本发明揭示了一种制备具有式（I）的孕烷衍生物的16，17-缩醛的过程，其中每个取代基都是独立选择的；R1为H或CH3；R2为C1-C6线性或支链烷基，炔基或环烷基；芳基或杂环芳基；或R1和R2结合形成饱和，不饱和C3-C6环或杂环；R3和R4相同或不同，分别表示H或卤素；R5为-OH或-OCOR，其中R表示H或C1-C6线性，支链或环烷基，可以被取代。
• 一种布地奈德工业化制备方法
  申请人：正大天晴药业集团股份有限公司

  公开号：CN109384827A

  公开（公告）日：2019-02-26

  本发明涉及一种布地奈德工业化制备方法。具体而言，本发明涉及在盐酸水溶液、二氯甲烷和乙腈中，16α‑羟基泼尼松龙与正丁醛反应制得布地奈德。本发明的方法具有在工业上可实施、重现性好等优势。
• [EN] STEROIDS AND PROTEIN-CONJUGATES THEREOF<br/>[FR] STÉROÏDES ET LEURS CONJUGUÉS PROTÉIQUES
  申请人：REGENERON PHARMA

  公开号：WO2018089373A9

  公开（公告）日：2018-07-12
• CORTICOSTEROID CONJUGATES AND USES THEREOF
  申请人：Teicher Martin H.

  公开号：US20100056488A1

  公开（公告）日：2010-03-04

  The invention features corticosteroids conjugated to either a charged group or a bulky group in a manner that resists in vivo cleavage, the resulting conjugate is a peripherally acting steroid with reduced activity in the central nervous system. The invention provides a method for treating a patient having an inflammatory disease by administering to the patient a corticosteroid conjugate.