Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation,in vitro and in vivo evaluation

 Meloxicam (MLX) is efficient in relieving pain and inflammatory symptoms, which, however, is limited by the poor solubility and gastrointestinal side effects. The objective of this study is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLX nanocrystals were successfully prepared by the nanoprecipitation technique based on acidbase neutralization. With poloxamer 407 and Tween 80 (80/20, w/w) as mixed stabilizers, MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure of MLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powder diffractometry. However,the nanoprecipitation process reduced the crystallinity of MLX. Nanocrystals increased both in vitro and in vivo transdermal permeation of MLX compared with the solution and suspension counterparts. Due to the enhanced apparent solubility and dissolution as well as the facilitated hair follicular penetration, nanocrystals present a high and prolonged plasma MLX concentration. And 2.58- and 4.4-fold increase in AUC0→24h was achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion, nanocrystal is advantageous for transdermal delivery of MLX.     

依托考昔和美洛昔康治疗急性痛风的临床效果以及安全性分析

目的比较依托考昔与美洛昔康治疗急性痛风的临床效果及其用药安全性。方法选择2010年1月-2013年1月本院收治的急性痛风患者120例为研究对象,随机分为依托考昔组及美洛昔康组,每组60例。依托考昔组服用依托考昔120 mg/d,美洛昔康组服用美洛昔康15 mg/d,测定患者疼痛的自我评分并记录药物不良反应。结果治疗后,两组患者的疼痛评分均下降,且依托考昔组的疼痛改善情况明显优于美洛昔康组（P〈0.05）。依托考昔组不良反应发生率为30.0%,美洛昔康组不良反应发生率为33.3%,两组差异无统计学意义（P〉0.05）。结论依托考昔治疗急性痛风的临床效果优于美洛昔康。     

Potential role of the compound Eucommia bone tonic granules in patients with osteoarthritis and osteonecrosis: A retrospective study

BACKGROUND Osteoarthritis is a major source of pain,disability,and socioeconomic cost worldwide.Osteonecrosis is a disabling disorder that frequently occurs in the younger population aged from 20-50 years.The compound Eucommia bone tonic granules,a traditional Chinese medicine,can alleviate the damage of osteoarthritis and osteonecrosis.AIM To investigate the potential role of the compound Eucommia bone tonic granules(Eucommia)in the treatment of patients with osteoarthritis and osteonecrosis.METHODS One-hundred forty osteoarthritis and osteonecrosis cases admitted to our hospital from January 2013 to December 2017 were selected.Patients were divided into two groups:Eucommia-meloxicam group and meloxicam group.Clinical efficacy and the Western Ontario and McMaster Universities Arthritis Index(WOMAC)score were evaluated according to the evaluation criteria of orthopedic diseases.The levels of bone-GLA protein,interleukin-17,recombinant human S100 calcium binding protein A12,sphingosine 1-phosphate,cystatin C,creatinine,and hemoglobin in peripheral blood were determined.RESULTS The total effective rate in the two osteoarthritis groups was not different,but the total effective rate in the two osteonecrosis groups was significantly different.The overall efficacy of Eucommia-meloxicam group was superior to that of the meloxicam group.WOMAC showed that pain,stiffness,and dysfunction in the two groups of osteoarthritis and osteonecrosis before and after treatment were significantly different.The concentration of recombinant human S100 calcium binding protein A12,sphingosine 1-phosphate,cystatin C,creatinine,and hemoglobin before and after treatment in the Eucommia-meloxicam group and meloxicam group of osteoarthritis and osteonecrosis were significantly different,and the two treatment groups were significantly different from each other for osteoarthritis.CONCLUSION Our findings indicate that Eucommia can effectively enhance the curative effect of meloxicam,and the combination of Eucommia and meloxicam is superior to meloxicam alone.     

美洛昔康对Aβ诱导阿尔茨海默病大鼠脑内一氧化氮的作用

目的：研究美洛昔康对β-淀粉样蛋白（Aβ）诱导的阿尔茨海默病（AD）模型大鼠脑内一氧化氮（NO）的作用,并探讨其抑制炎症作用的机制。方法：采用Aβ1-40海马注射建立AD大鼠模型。术后第2天各组大鼠灌胃给药,连续30d。美洛昔康小、中、大剂量分别为：1、2、4mg/（kg·d）。生理盐水（NS）对照组及模型对照组分别给予等容量NS及0.5%羧甲基纤维素钠溶液。电迷宫刺激器检测大鼠学习记忆能力;生化法检测脑组织中NO的含量变化。结果：美洛昔康能提高AD大鼠的学习记忆能力;抑制AD大鼠脑内的表达。结论：美洛昔康可能通过抑制NO的分泌,改善大鼠的学习记忆能力。     

美洛昔康醇质体凝胶的研制

目的：制备美洛昔康醇质体凝胶。方法：通过正交设计优选出美洛昔康醇质体的制备工艺,利用HPLC法测定包封率,并对其进行外观粒径评价,从而制备出凝胶剂。结果：制备的醇质体粒径分布均匀,平均粒径为16.95μm,包封率为74.70%。制得凝胶剂为半透明黏稠状胶体,平均含量为2.17 mg/10 g。结论：本实验制备工艺简单,制得的美洛昔康醇质体凝胶有很好的稳定性,具有较好的应用前景。     

COX-2抑制剂对慢性铝过负荷大鼠海马5-脂氧酶表达的影响

目的探讨COX-2抑制剂美洛昔康对慢性铝过负荷大鼠海马5-LO表达的影响。方法葡萄糖酸铝灌胃给予Wistar大鼠,1次/d,每周5 d,连续20 w,建立慢性铝过负荷致神经元退变大鼠模型。美洛昔康(1和3 mg/kg),在每次给予铝盐后30 min灌胃给予。RT-PCR检测大鼠海马5-LO mRNA的表达变化,Western印迹方法检测5-LO蛋白表达情况。结果慢性铝过负荷致大鼠海马5-LO mRNA和蛋白表达明显增加。美洛昔康能明显阻遏慢性铝过负荷诱导的大鼠海马5-LO mRNA和蛋白表达的增加。结论 COX-2抑制剂明显下调慢性铝过负荷大鼠海马5-LO表达。     

Labeling and evaluation of 99mTc‐tricarbonyl‐meloxicam as a preferential COX‐2 inhibitor for inflammation imaging

Imaging of inflammation has an important role in dissolving problems in diagnosis and therapy of patients with inflammatory disorders. In this study meloxican as a nonsteroidal anti‐inflammatory drug (NSAID) has been labeled with thechnetium‐99m‐tricarbonyl core ([^99mTc (CO)₃ (H₂O)₃]⁺) in order to evaluate its feasibility as an inflammation imaging agent for in vivo use. ^99mTc‐tricabonyl labeling of meloxicam was performed by its incubation with prepared precursor ^99mTc‐tricabonyl and heating in a boiling water bath for 30 min while various range of pH (1–9) was adjusted. The stability of ^99mTc‐tricarbonyl‐Meloxicam was checked in human serum at 37 °C, and biodistribution was studied in mice. Labeling yield of 98.1 ± 0.4% was obtained corresponding to a specific activity of 0.14 GBq/µmol. The radioconjugate showed good stability in human serum. Our main achievement was high accumulation of ^99mTc‐tricarbonyl‐Meloxicam in the inflammated muscle in mice (T/NT = 3.90 at 4 h post injection) which may diagnostically be beneficial for distinguish sites of inflammation.     

Development and validation of ultra-performance liquid chromatography method for the determination of meloxicam and its impurities in active pharmaceutical ingredients

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美洛昔康片剂溶出度测定方法的研究

目的：建立完善美洛昔康片的溶出度测定方法。方法：按要求根据中华人民共和国药典1995年版二部附录XC第二法测定溶出度。结果：美洛昔康片在30min时，累积溶出接近平衡，累计溶出量在90％以上，回收率101．8％，RSD为0．6％。结论：该方法简便，可靠，可用于美洛昔康片的溶出度测定。     

两种方案治疗类风湿性关节炎的成本-效果分析

目的研究两种方案治疗类风湿性关节炎（RA）的经济效果和安全性。方法选择病情处于活动期的RA患者120例,随机分为来氟米特组和美洛昔康组,每组60例。基础用药与检查各组均相同。运用药物经济学的成本-效果分析方法对各组进行评价。结果两组方案治疗RA的成本平均每例分别为：来氟米特组（3007.49±590.12）元,美洛昔康组（2656.34±542.56）元;有效率依次为88.3%、80.0%;每获得一个单位效果,依次需花费成本34.06元、33.20元;不良反应的发生率依次为：5.0%、13.3%。结论美洛昔康组成本较低,但有效率较低,不良反应较多;来氟米特组虽成本较高,但有效率较高,不良反应较少。RA患者选用来氟米特组为宜。