降钙素联合盐酸氨基葡萄糖治疗膝骨关节炎的临床效果研究

目的:分析降钙素联合盐酸氨基葡萄糖在治疗膝骨关节炎中的临床效果.方法:选取所在医院2015年10月～2017年3月92例膝骨关节炎患者,双盲法纳入实验组与对照组,实验组(n=46)给予降钙素+盐酸氨基葡萄糖,对照组(n=46)单纯采用盐酸氨基葡萄糖治疗,对比两组临床疗效.结果:实验组与对照组临床总有效率(93.48％VS76.09％)存在明显差异(P<0.05);实验组治疗后VAS疼痛评分、HSS膝关节功能评分均优于对照组,组间对比存在显著差异(P<0.05).结论:降钙素联合盐酸氨基葡萄糖临床效果确切,能够提高膝骨关节炎治疗效果,改善疼痛及关节功能.     

毛细管电泳间接紫外检测法测定氨基葡萄糖制剂的含量

目的:建立毛细管电泳间接紫外检测法测定氨基葡萄糖含量.方法:背景电解质溶液为60mmol/L吡啶二羧酸-0.3mmol/L十六烷基三甲基溴化铵,pH12.30.结果:氨基葡萄糖在0.5～5mg/mL浓度范围内线性关系良好.方法精密度RSD为2.3％,平均加样回收率为99.65％,RSD为1.8％(n=3).结论:该法专属性强、重现性好.可以作为一种简单、快速的方法控制氨基葡萄糖制剂的质量.     

如意金黄膏联合盐酸氨基葡萄糖治疗膝骨性关节炎疗效观察

目的 探讨如意金黄膏外敷联合盐酸氨基葡萄糖口服治疗膝骨性关节炎的疗效.方法 选择膝骨性关节炎患者200例,按照就诊顺序分为两组,各100例.对照组予以口服盐酸氨基葡萄糖,每次1粒,3次/d,6周为1个疗程,每年2个疗程.治疗组在对照组口服盐酸氨基葡萄糖基础上外敷如意金黄膏,隔日更换1次,14 d为1个疗程,每年2个疗程.结果 两组患者均随访1年,治疗组治疗有效率(85.0％)明显高于对照组(73.0％)(x2=4.34,P＜0.05).结论 如意金黄膏外敷联合盐酸氨基葡萄糖口服治疗膝骨性关节炎能明显改善患者的临床症状,疗效优于单纯的盐酸氨基葡萄糖口服治疗.     

星点设计-效应面法优化盐酸氨基葡萄糖凝胶剂处方及透皮吸收研究

目的:对盐酸氨基葡萄糖凝胶剂处方进行优化.方法:以卡波姆980NF(X1,g)、氮酮(X2,g)及丙二醇(X3,ml)的加入量为考察因素,盐酸氨基葡萄糖体外透皮累积释放为优化指标指标,应用星点设计-效应面法筛选最佳处方,并对优化处方进行验证.结果:最优处方组成:卡波姆980NF l.72 g,氮酮3.67 g,丙二醇16.89 ml.该处方的8h累积透药百分比达80.1％,实测值与预测值无明显差异.结论:采用星点设计-效应面法得到了盐酸氨基葡萄糖凝胶剂的处方优化模型,实现了处方优化.     

反相高效液相色谱法测定硫酸氨基葡萄糖泡腾片中硫酸氨基葡萄糖的含量

目的:建立硫酸氨基葡萄糖含量测定的反相高效液相色谱分析方法.方法:样品柱前衍生化后采用反相高效液相色谱进行测定,使用Hypersil ODS色谱柱(4.6 mm×50 mm,3μm),流动相为三水合乙酸钠溶液-甲醇(90∶10),用紫外检测器检测.结果:方法的进样量线性范围为0.399～1.597 mg/mL(r=0.9993),回收率为98％～ 102％.结论:此法简便、快速、准确,是测定硫酸氨基葡萄糖泡腾片含量的有效方法,并可用于硫酸氨基葡萄糖含量的测定.     

盐酸氨基葡萄糖治疗对膝关节半月板损伤患者康复效果的影响

目的:探究盐酸氨基葡萄糖治疗对膝关节半月板损伤患者康复效果的影响.方法:以2015年1月～2016年12月为时间区间,选择60例膝关节半月板损伤患者,按照入院先后顺序分为参照组、研究组,各30例,分别予以双醋瑞因、盐酸氨基葡萄糖治疗,对比康复效果.结果:研究组VAS评分、Lysholm功能评分、不良反应发生率分别为(1.67±0.87)分、(86.53±8.74)分、3.33％(1/30),参照组分别为(4.89±1.01)分、(55.92±10.61)分、20.00％(6/30),研究组VAS评分、 不良反应发生率明显低于参照组,而Lysholm功能评分明显高于参照组,差异明显,(P<0.05).结论:予以膝关节半月板损伤盐酸氨基葡萄糖治疗,可缓解疼痛,改善膝关节功能,降低不良反应发生率,促进康复,临床应用价值高.     

盐酸氨基葡萄糖联合双醋瑞因治疗膝骨性关节炎临床疗效观察

目的 观察盐酸氨基葡萄糖联合双醋瑞因治疗膝骨性关节炎(KOA)的临床疗效.方法 选取2014年1月至2015年8月期间江苏省中医院收治的60例膝骨性关节炎患者,随机分为对照组与观察组各30例.对照组给予盐酸氨基葡萄糖单药治疗,每天两次,每次750mg;观察组在对照组基础上加用双醋瑞因治疗,每天一次,每次50mg.对比治疗前后两组患者的Lequesne评分.结果 两组患者治疗后Lequesne评分均低于治疗前,差异具有统计学意义(P＜0.05);治疗14 d、28 d后观察组Lequesne评分均低于对照组,差异具有统计学意义(P＜0.05).对照组不良反应率为13.33％,观察组不良反应率为16.67％,两组患者的不良反应发生率无显著差异(P＞0.05).结论 盐酸氨基葡萄糖联合双醋瑞因治疗膝骨性关节炎有效,临床疗效较单用盐酸氨基葡萄糖更好,且安全性未降低,值得进一步临床推广.     

盐酸氨基葡萄糖片的相对生物利用度及其生物等效性评价

目的研究盐酸氨基葡萄糖片在健康人体内的药物动力学及相对生物利用度。方法采用液相色谱质谱质谱联用法测定了18名健康男性受试者口服盐酸氨基葡萄糖片和盐酸氨基葡萄糖胶囊后不同时间血浆中氨基葡萄糖的质量浓度,并求出主要药物动力学参数。结果血浆中氨基葡萄糖的tmax分别为(3.1±0.7)和(2.9±0.8)h,ρmax分别为(636.5±310.1)和(666.0±371.3)μg.L-1,t1/2分别为(0.9±0.2)和(1.1±0.4)h,AUC0-12分别为(1 896±809.7)和(1 967±858.2)μg.h.L-1。氨基葡萄糖的相对生物利用度为(96.8±9.7)%。结论根据双单侧检验表明两种制剂具有生物等效性。     

关节镜下清理术、关节腔内注射玻璃酸钠联合口服氨基葡萄糖和塞来昔布治疗膝关节炎的临床效果

目的 探讨关节镜下清理术、关节内注射玻璃酸钠联合口服氨基葡萄糖和塞来昔布治疗膝关节炎的临床效果.方法 选取2012年12月～2014年5月两院(赣南医学院第一、二附属医院)收治的400例膝关节炎患者为研究对象,以抽签法将患者随机分为观察组与对照组,每组各200例.对照组单用关节镜下清理术,观察组在对照组基础上增加玻璃酸钠、塞来昔布和氨基葡萄糖进行治疗,比较两组患者的疼痛评分、总满意度.结果 治疗后,观察组的VAS评分为(2.45±0.61)分,WOMAC评分为(17.5±7.67)分,均显著低于对照组的(5.62±1.21)、(26.74±10.64)分,差异有统计学意义(P＜0.01),观察组的总满意度为99.5％,显著高于对照组的93.5％,差异有统计学意义(P＜0.01).结论 关节镜下清理术联合玻璃酸钠、塞来昔布和氨基葡萄糖治疗膝关节炎的效果可靠,可有效缓解疼痛,具有较高的临床应用价值.     

D-氨基葡萄糖硫酸钾盐含量测定方法探讨

目的 对D-氨基葡萄糖硫酸钾盐的含量测定方法的适用性进行验证.方法 采用Zorbax C8(4.6 mm×250 mm,5 μm)色谱柱,流动相为乙腈-0.05%磷酸(pH=3.0)(40:60),流速0.6 mL·min-1,检测波长195 nm.结果 D-氨基葡萄糖盐酸盐对照品和D-氨基葡萄糖硫酸钾盐样品图谱中的主峰可能不是D-氨基葡萄糖峰,而是Cl-峰; 在药典规定的色谱条件下,D-氨基葡萄糖硫酸钾盐中的SO42-峰与主峰Cl-峰重叠,干扰主峰的测定.结论 需进一步改进和完善D-氨基葡萄糖硫酸钾盐的含量测定方法.     

HPLC法测定氨糖美辛肠溶片中盐酸氨基葡萄糖的含量

目的建立HPLC法测定氨糖美辛肠溶片中盐酸氨基葡萄糖的含量。方法采用高效液相色谱法,色谱柱为C18柱（250×4.6mm,5μm）;流动相为乙腈-0.05%磷酸溶液（40：60）并用三乙胺调至pH3.0;流速为0.6ml·min^-1;检测波长为192nm;柱温为30℃。结果在1.31～20.6μg范围内盐酸氨基葡萄糖的浓度与峰面积呈良好的线性关系（r=0.9994,n=6）;平均回收率为99.57%（n=9,RSD=0.91%）。结论本法简便、准确、重复性好,适用于氨糖美辛肠溶片中盐酸氨基葡萄糖的含量测定。     

LC-MS/MS法测定人血浆中硫酸氨基葡萄糖浓度及其药动学研究

目的:建立测定人血浆中硫酸氨基葡萄糖浓度的方法,并考察其药动学特征。方法:采用高效液相色谱串联质谱电喷雾检测(LC-MS/MS)法,色谱柱为Phenomenex ODS,流动相为甲醇-0.2%醋酸铵-0.1%甲酸缓冲液(梯度洗脱),流速为1.0mL.min-1;电喷雾电离源,正离子模式下以选择反应监测(SRM)方式进行监测。以DAS2.0软件进行房室模型拟合,计算主要药动学参数。结果:在选定的色谱及质谱条件下,硫酸氨基葡萄糖与内标及血浆杂质分离良好,氨基葡萄糖增量浓度在8.27～165、165～8268ng.mL-1范围内线性关系良好。方法回收率为103.8%～113.7%,日内和日间RSD均<20%。健康受试者单剂量口服低、中、高剂量(500、1000、1500mg)复方硫酸氨基葡萄糖分散片后的药-时曲线符合非房室模型,主要药动学参数分别为:t1/2为(1.2±0.4)、(1.3±0.4)、(1.4±0.9)h,tma(x2.6±1.4)、(2.7±0.9)、(1.9±0.8)h,cma(x417±193)、(795±281)、(925±282)ng.mL-1,AUC0～1(01416±201)、(3366±1020)、(4033±1282)ng.h.mL-1,MRT0～1(03.2±0.7)、(3.6±0.2)、(3.3±0.6)h;多剂量口服低剂量(每次500mg,tid)复方硫酸氨基葡萄糖分散片达到稳态后,主要药动学参数为:cssma(x294±75.6)ng.mL-1,cssmi(n59.4±55.7)ng.mL-1,tma(x1.9±1.1)h,t1/(21.4±0.8)h,AUC0～1(01015±243)ng.h.mL-1,AUCs(s1000±244)ng.h.mL-1,cssa(v125±30.6)ng.mL-1,MRT0～1(02.7±0.3)。结论:本方法适用于复方硫酸氨基葡萄糖分散片人体内药动学研究。健康受试者单剂量口服本品后,氨基葡萄糖的吸收程度(AUC0～t和cmax)与剂量在试验设计的剂量范围内存在一定的线性关系;连续口服本品后,在体内基本无积蓄现象。     

积分脉冲安培检测-高效阴离子交换色谱法测定盐酸氨基葡萄糖口腔崩解片含量

目的建立测定盐酸氨基葡萄糖口腔崩解片含量的方法。方法采用积分脉冲安培检测-高效阴离子交换色谱法测定盐酸氨基葡萄糖,优化了淋洗条件和积分脉冲安培检测条件。结果盐酸氨基葡萄糖的检测限为0.05 ng,线性范围为0.1~40μg/mL,盐酸氨基葡萄糖口腔崩解片的加样回收率为100.1%,RSD为1.17%(n=9)。结论此法可简单、快速、灵敏、准确地测定盐酸氨基葡萄糖口腔崩解片的含量。     

Application of a liquid chromatographic/tandem mass spectrometric method to a kinetic study of derivative glucosamine in healthy human urine

A sensitive, selective and efficient liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of glucosamine in healthy human urine. Urine samples were extracted by acetonitrile and derivatized with o-phthalaldehyde/3-mercaptopropionic acid. Analysis was then carried out using ESI source and methanol/0.2% ammonium acetate-0.1% formic acid mobile phase gradient elution, with tolterodine tartrate as the internal standard. The linear calibration curve ranged from 0.41μg/ml to 82.7μg/ml. The intra-day and inter-day precisions were less than 3.93% and 10.0%, respectively. The extraction recoveries determined at three concentration levels were higher than 88.6%. The method was successfully applied for determining the urine concentration of glucosamine up to 24h after oral administration of 1g glucosamine sulfate dispersible table (containing 785.08mg glucosamine) from a clinical pharmacokinetic study in healthy volunteers.     

氨基葡萄糖与硫酸软骨素复方片的抗炎、镇痛作用

目的将氨基葡萄糖与硫酸软骨素制成复方片剂,考察其抗炎与镇痛作用。方法氨基葡萄糖与硫酸软骨素按5∶4的比例压片制成复方片剂。以SD大鼠为实验动物,建立足趾肿胀模型进行抗急性炎症实验;采用棉球植入法进行抗慢性炎症实验;以ICR小鼠为实验动物,建立小鼠疼痛模型进行镇痛实验。结果给药28 d,足趾肿胀1 h,低、中、高剂量组足趾肿胀度明显小于正常对照组(P<0.05)。大鼠肉芽肿实验结果显示各给药组与正常组相比能明显抑制大鼠肉芽肿(P<0.05)。醋酸致小鼠扭体实验显示各给药组与对照组比较,对醋酸致小鼠扭体次数有明显的抑制(P<0.05)。结论氨基葡萄糖与硫酸软骨素复方片具有抗炎作用;对醋酸致小鼠疼痛模型具有镇痛作用。     

柱前衍生化法测定盐酸氨基葡萄糖软膏的含量

目的建立柱前衍生化RP-HPLC法测定盐酸氨基葡萄糖软膏的含量。方法采用NH2色谱柱(250 mm×4.6 mm,5μm),流动相为乙腈-水(体积比90∶10),流速为1.0 mL.min-1,衍生化试剂为异硫氰酸苯酯,检测波长254 nm。结果在本色谱条件下,盐酸氨基葡萄糖质量浓度在12.75~38.25 mg.L-1内呈良好的线性关系,回收率为100.4%。结论该方法准确、可靠,适用于盐酸氨基葡萄糖软膏的含量测定。     

The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to beagle dogs

OBJECTIVE: The purpose of this study was to determine the oral bioavailability and pharmacokinetics of a glucosamine (GL) and the disaccharides of chondroitin sulfate (CS) after single and multiple-dosing of a GL/CS combination (Cosamin, Cosequin). METHODS: Male beagle dogs (n = 8, 12 kg) received the following treatments: (1) IV GL (500 mg)/CS (400 mg), (2) p.o. GL (1500 mg)/CS (1200 mg), (3) p.o. GL (2000 mg)/CS (1600 mg), (4) p.o. GL (1500 mg)/CS (1200 mg) QD for days 1-7 and p.o. GL (3000 mg)/CS (2400 mg) from days 8 to 14. Blood samples were collected over 24 h and glucosamine and the disaccharides of chondroitin sulfate were determined. Pharmacokinetic analysis was performed on glucosamine and total chondroitin sulfate disaccharides and parameters were compared across treatments using ANOVA with post hoc analysis. RESULT: After the IV administration, glucosamine declined rapidly in a bi-exponential fashion with a mean (+/- S.D.) elimination t(1/2) of 0.52 (0.25) h. GL absorption was relatively fast (C(max) = 8.95 microg/ml, and T(max) 1.5 h after 1500 mg dose) and the mean bioavailability of glucosamine after single dosing was approximately 12%. The extent of absorption of chondroitin sulfate as indicated by the mean C(max) (21.5 microg/ml) and mean AUC (187 microg/ml h) of total disaccharides after dosing (1600 mg) provides evidence that chondroitin sulfate is absorbed orally. The bioavailability of CS ranged from 4.8 to 5.0% after single dosing and 200-278% upon multiple dosing. CONCLUSION: The results of this study show that both glucosamine and chondroitin sulfate (measured as total disaccharides) are bioavailable after oral dosing. In addition, the low molecular weight chondroitin sulfate used in this study displays significant accumulation upon multiple dosing.     

Development of a simple analytical methodology for determination of glucosamine release from modified release matrix tablets

A simple spectrophotometric method for determination of glucosamine release from sustained release (SR) hydrophilic matrix tablet based on reaction with ninhydrin is developed, optimized and validated. The purple color (Ruhemann purple) resulted from the reaction was stabilized and measured at 570 nm. The method optimization was essential as many procedural parameters influenced the accuracy of determination including the ninhydrin concentration, reaction time, pH, reaction temperature, purple color stability period, and glucosamine/ninhydrin ratio. Glucosamine tablets (600 mg) with different hydrophilic polymers were formulated and manufactured on a rotary press. Dissolution studies were conducted (USP 26) using deionized water at 37+/-0.2 degrees C with paddle rotation of 50 rpm, and samples were removed manually at appropriate time intervals. Under given optimized reaction conditions that appeared to be critical, glucosamine was quantitatively analyzed and the calibration curve in the range of 0.202-2.020 mg (r=0.9999) was constructed. The recovery rate of the developed method was 97.8-101.7% (n=6). Reproducible dissolution profiles were achieved from the dissolution studies performed on different glucosamine tablets. The developed method is easy to use, accurate and highly cost-effective for routine studies relative to HPLC and other techniques.     

Development and validation of a HPLC–ES-MS/MS method for the determination of glucosamine in human synovial fluid

A new HPLC method for the determination of glucosamine (2-amino-2-deoxy-d-glucose) in human synovial fluid was developed and validated. Synovial fluid samples were analyzed after a simple protein precipitation step with trichloroacetic acid using a polymer-based amino column with a mobile phase composed of 10 mM ammonium acetate (pH 7.5)–acetonitrile (20:80, v/v) at 0.3 mL/min flow rate. d-[1-¹³C]glucosamine was used as internal standard. Selective detection was performed by tandem mass spectrometry with electrospray source, operating in positive ionization mode and in multiple reaction monitoring acquisition (m/z 180 → 72 and 181 → 73 for glucosamine and internal standard, respectively). The limit of quantification (injected volume = 3 μL) was 0.02 ng, corresponding to 10 ng/mL in synovial fluid. Calibration curves obtained using matrix-matched calibration standards and internal standard at 600 ng/mL were linear up to 2000 ng/mL. Precision values (%R.S.D.) were ≤14% in the entire analytical range. Accuracy (%bias) ranged from −11% to 10%. The recoveries measured at three concentration levels (50, 800, and 1500 ng/mL) were higher than 89%. The method was successfully applied to measure endogenous glucosamine levels in synovial fluid samples collected from patients with knee osteoarthritis and glucosamine levels after oral administration of glucosamine sulfate (DONA^®) at the dose of 1500 mg/day for 14 consecutive days (steady-state).