曲安奈德联合甲氨喋呤关节腔注射治疗类风湿关节炎

目的探讨联合使用甲氨喋呤(MTX)和曲安奈德(TA)关节腔注射治疗类风湿关节炎(RA)的疗效。方法选择2006年1月-2007年4月我院门诊对称性腕或膝关节炎的RA患者37例。选择一对炎症程度相当的膝或腕关节,随机确定一侧,以曲安奈德针(TA)1mL:40mg溶解MTX针(MTX)5mg混匀后关节腔注射(TM组)。对侧作为对照,以相同剂量曲安奈德针关节腔注射(TA组),整体治疗不变,继续按原来方法服用NSAIDs及DMARDs治疗。分别于注射后第1个月、3个月、6个月末观察注射关节的肿胀数、疼痛数、压痛数及相应指数。结果TM组与TA组关节腔注射后,肿胀关节明显减少,而不同时间点两组间差异均有统计学意义(P<0.01)。随访6个月,两组均未发现明显不良反应。结论曲安奈德针联合MTX针关节腔注射治疗类风湿关节炎,其消炎、止痛、消肿和改善患者关节功能的疗效优于单用曲安奈德针关节腔注射,可显著减少复发机会,延迟复发时间,是类风湿关节炎有效的控制方法之一。     

透明质酸钠关节腔内注射致过敏反应

1例71岁男性患者因膝关节骨性关节炎入院给予透明质酸钠20 mg右膝关节腔内注射。第1次治疗后患者无明显不适。6 d后,第2次膝关节腔内注射透明质酸钠20 mg。注射后约5 h,患者突然出现寒战、心慌、呼吸困难,血压96/60 mm Hg(1 mmHg=0.133 kPa)。立即给予吸氧等对症治疗,1 h后症状逐渐缓解,血压105/70 mm Hg。住院期间未再应用该药,未再发生上述不良反应。共住院2周出院。     

Pharmacokinetic study of methotrexate following intra-articular injection of methotrexate loaded poly(L-lactic acid) microspheres in rabbits

The pharmacokinetics and tissue distribution of methotrexate (MTX) were investigated following intra-articular injection of either MTX solution or controlled release MTX loaded microspheres in healthy rabbit joints. MTX solution or MTX loaded microspheres (size 30-100 mum) (10 mg MTX) was injected into the right knee joint cavity of rabbits. Blood samples were taken at predetermined times from the jugular vein. Urine samples were also collected over time periods up to 24 h. The major organs and synovial tissues were removed for analysis 6 and 24 h post-injection (n = 4). MTX and 7-OH-MTX concentrations in the plasma and major organs were determined by HPLC. The MTX plasma area under the concentration-time curve (AUC) for rabbits injected with MTX solution was seven fold higher than that of the rabbits injected with MTX microspheres, while t(1/2) and mean residence time (MRT) were not significantly different between two treatment groups. Four fold more MTX was excreted in the urine from rabbits injected with MTX solution compared to those injected with MTX loaded microspheres 24 h following intra-articular injection. The concentration of MTX in the synovial tissues following intra-articular injection was significantly higher in the rabbits injected with microspheres than in the rabbits injected with MTX solution. MTX solution was rapidly cleared from the joint cavity while MTX encapsulated microspheres retained MTX in the joint cavity.     

Evaluation of reconstituted Sendai virus envelopes as intra-articular drug vectors: effects on normal and experimentally arthritic rabbit knee joints

Fusogenic vesicles reconstituted from the envelopes of Sendai virus particles were injected into rabbit knee joints (both normal and experimentally arthritic) to evaluate the in-vivo biocompatibility of these putative drug carriers. The reconstituted Sendai virus envelopes (RSVE) were greater than 80% retained within the arthritic knee joints after 24 h and studies with 125I- and fluorescein-labelled RSVE both showed association of the vesicles with the synovia of arthritic and healthy joints. However, RSVE were found to cause inflammation after intra-articular injection, as judged by joint swelling and histological assessment, and these effects were exacerbated by successive administrations. RSVE-entrapped methotrexate, whether free or conjugated to human serum albumin, was ineffective in preventing the irritancy of RSVE or in reducing the chronic inflammation in joints affected by an experimentally induced arthritis.     

玻璃酸钠治疗症状性膝骨关节炎55例临床观察

目的：观察玻璃酸钠(HA)治疗症状性膝骨关节炎(OA)的临床疗效。方法：55例症状性膝OA关节腔内注射姒，每周1次，5周为一疗程，完成治疗后每月随诊1次。记录治疗前后的关节痛或不适(包括步行痛、夜间痛等)、晨僵、步行距离、关节活动度等。结果：完成治疗后缓解率为30．9％，有效率为89．1％。重度OA治疗有效率为73．3％，较轻中度OA明显偏低。同时应用糖皮质激素者显效时间缩短。结论：姒对轻、中度OA疗效好，适宜与糖皮质激素联用，且有一定的远期疗效。     

兔膝关节腔内注射黄原胶的安全性评价

目的评价兔膝关节腔注射黄原胶的安全性。方法在兔膝关节腔分别注射2%,1%和0.5%的黄原胶注射液和生理盐水0.1 mL/kg,每周1次,连续5周。检测兔膝关节宽度、血液学和血液生化参数并观察肝、肾、膝关节组织病理学变化。结果与生理盐水组比,不同剂量黄原胶组膝关节宽度、血液学及血液生化参数等均无明显改变;肝、肾及关节组织未见明显病理改变。结论在兔膝关节腔注射黄原胶(0.5%～2%)0.1 mL/kg,每周1次,连续5周,全身及局部未见明显毒性作用。     

Pharmacokinetics of rimexolone after intra-articular administration

The pharmacokinetics of rimexolone were investigated after intra-articular injection into the knee joints of patients with rheumatoid arthritis. After a single dose of 40 mg rimexolone the drug could be detected in plasma over 3 months. The suspension dissolves in the synovia very slowly and provides a sustained release of the steroid in the joint. Pharmacokinetic analysis was performed on the assumption that the disposition of rimexolone after intra-articular administration is absorption limited ("flip-flop-case"). Dose linearity was studied in a range from 40 to 200 mg. Total body clearance averaged 106 L/h and was independent of dose. The mean residence time of rimexolone in the knee joint is very long and averaged 25 days. It could be shown that the mean residence time of different glucocorticoids correlates well with the duration of their clinical effectiveness.     

Anti-inflammatory effect of THS-201, a new intra-articular steroid

The effect of THS-201, a new intra-articular steroid, on inflammations was examined using acute, subacute and chronic experimental models, and the antiinflammatory action of THS-201 was compared with those of reference steroids such as triamcinolone acetonide (TA), methylprednisolone acetate (MPA), hydrocortisone acetate (HA) and halopredone (HP). Reference steroids, which were given s.c. or locally, dose-dependently inhibited carrageenin-induced foot-pad edema, sodium carboxymethyl cellulose-induced leukocyte migration, cotton pellet granuloma and carrageenin granuloma pouch in rats. Although the inhibitory effects of reference steroids on such inflammations were unrelated to their administration routes, the inhibitory potency decreased in the following order: TA greater than MPA greater than HA = HP. THS-201 even at a dose of 100 mg/kg had no inhibitory effects on such inflammations when given s.c. By contrast, THS-201 given locally had anti-inflammatory actions: the inhibitory potency of THS-201 in chronic models was higher than that of TA, but was lower in the acute models than that of HA. In antigen-induced arthritis in rabbits, the inhibition of swelling of inflamed joints by intra-articular injection of THS-201 (2 mg/joint) persisted more than 30 days, suggesting that the elimination of THS-201 from the injected site was very slow. In contrast to the finding of reference steroids, THS-201 showed no systemic adverse reactions in all experiments. The results, which are in agreement with the findings of labeled THS-201 into arthritic joints, indicate that THS-201 can strongly inhibit recurrence of inflammation as compared with reference steroids tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

透明质酸膝骨关节腔内注射治疗膝骨关节炎

目的：研究透明质酸膝骨关节腔内注射治疗膝骨关节炎的疗效。方法：９０例膝骨关节炎病人，男性３８例，女性５２例，年龄６５±ｓ８ａ，随机分为Ａ，Ｂ，Ｃ３组，每组３０例，分别采用透明质酸关节腔内注射，２．５ｍＬ，ｑｗ×３ｗｋ；双氯芬酸５０ｍｇ，ｐｏ，ｂｉｄ×３ｗｋ；关节腔内注射曲安奈德注射液２０ｍｇ＋０．５％布比卡因注射液５ｍＬ＋０．９％氯化钠注射液至２０ｍＬ，ｑｗ×３ｗｋ。结果：Ａ，Ｂ，Ｃ３组有效率分别为９７％，８７％和９０％。Ｂ，Ｃ２组与Ａ组比较，差别有显著意义（Ｐ＜０．０５）。３组副作用均轻微。结论：透明质酸关节腔内注射是治疗膝骨关节炎较为有效的方法。     

Therapeutic synergism between hyaluronic acid and dexamethasone in the intra-articular treatment of osteoarthritis of the knee: a preliminary open study.

In vitro studies on the effects of dexamethasone on human synovial cells have shown that with high concentrations of the steroid in the culture medium cellular activity was completely blocked whereas with low concentrations (10(-6)M), cellular density decreased but there was an increase in the synthesis of RNA, DNA, protein and hyaluronic acid. These data, coupled with clinical experience of using intra-articular hyaluronic acid to treat patients with osteoarthritis of the knee, prompted the investigators to carry out an open, randomized study of the use of very small doses of dexamethasone in association with hyaluronic acid in 40 osteoarthritic patients. Twenty patients received a weekly intra-articular injection of 20 mg sodium hyaluronate in 2 ml phosphate buffer for 5 weeks; the other 20 patients followed a similar treatment regimen, the only difference being the addition of 0.4 mg dexamethasone phosphate to the first injection. Clinical examination of the knee was made before each injection, 7 days after the fifth injection and 60 days after the start of the trial. Rating scale assessments were made at each visit of spontaneous pain, pain during the day, at night, weight bearing and whilst walking. The results showed that whilst a progressive decrease in all pain parameters was evident and persisted after the end of treatment in both patient groups, pain intensity decreased more rapidly and to lower levels in all but weight-bearing pain, as did improvement in joint mobility, in the combined treatment group. Local tolerance was good with both treatment regimens, with no untoward signs or symptoms at any time.(ABSTRACT TRUNCATED AT 250 WORDS)     

臭氧配合玻璃酸钠关节内注射治疗膝关节骨性关节炎220例临床观察

目的探讨臭氧配合玻璃酸钠关节内注射治疗膝关节骨性关节炎的临床疗效及治疗机理。方法将220例膝关节骨性关节炎患者随机分为臭氧组和对照组,每组110例。臭氧组采用医用臭氧配合玻璃酸钠关节内注射;对照组采用单纯玻璃酸钠关节内注射。结果臭氧组总有效率为84.5%高于对照组的70.0%,差异有统计学意义（P〈0.05）。结论臭氧配合玻璃酸钠关节内注射是治疗老年退行性膝关节炎较好的方法。     

Methotrexate loaded poly(L-lactic acid) microspheres for intra-articular delivery of methotrexate to the joint

A controlled release delivery system that localizes methotrexate (MTX) in the synovial joint is needed to treat inflammation in rheumatoid arthritis (RA). The purpose of this work was to develop and characterize MTX loaded poly(l-lactic acid) (PLLA) microspheres and evaluate in vivo tolerability and MTX plasma concentrations following intra-articular injection into healthy rabbits. MTX loaded PLLA (2 kg/mole) microspheres were prepared using the solvent evaporation method and characterized in terms of size, molecular weight, thermal properties, and release rates into phosphate buffered saline (PBS) (pH 7.4) at 37 degrees C. Biocompatibility was evaluated by observing the swelling of the joints of the rabbits and histological analysis following the injection of the microspheres. MTX concentrations in the plasma and urine samples of rabbits were evaluated by high-performance liquid chromatography (HPLC). MTX loaded microspheres showed a rapid burst phase followed by a slow release phase. MTX loaded and control microspheres were biocompatible and plasma concentrations of MTX were tenfold higher in rabbits injected intra-articularly with free MTX than MTX microspheres. MTX microspheres may retain the drug in the joint by reducing clearance from the joint into the blood.     

关节腔注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合复方倍他米松治疗类风湿关节炎膝关节炎的临床观察

目的评价关节腔注射重组人Ⅱ型肿瘤坏死因子受体- 抗体融合蛋白联合复方倍他米松对类风湿关节炎膝关节炎的疗效及安全性.方法：对具有膝关节炎的24 例类风湿关节炎患者行膝关节腔穿刺,注入重组人Ⅱ型肿瘤坏死因子受体- 抗体融合蛋白25 mg与复方倍他米松7 mg,注射前及注射后4 周与8 周评估关节病变情况.结果：注射治疗4 周与8 周后患者关节疼痛评分、肿胀指数、压痛指数均较治疗前明显改善,差异具有统计学意义（P 〈 0.05）;治疗前、治疗后4 周及治疗后8 周患者膝关节平均滑膜厚度分别为（6.7 ± 2.0）、（5.8 ± 2.2）、（4.2 ± 2.3） mm,膝关节滑膜增厚明显减轻,治疗前与治疗后4 周乃至8 周比较,差异具有统计学意义（P 〈 0.05）.结论：关节腔注射重组人Ⅱ型肿瘤坏死因子受体- 抗体融合蛋白联合复方倍他米松可减轻关节炎症,安全性较好.     

玻璃酸钠单独使用与联合使用复方倍他米松关节内注射治疗膝骨关节炎的疗效对比

目的:分别探讨玻璃酸钠及玻璃酸钠联合复方倍他米松关节内注射治疗膝关节骨关节炎的疗效。对比上述两种方法的疗效有无差异。探讨两种方法短期疗效与膝关节骨关节炎病情轻重有无关系。方法:选择膝关节骨关节炎病人80例,随机分为A组和B组,其中A组43个膝(双膝13例),治疗方法为玻璃酸钠(阿尔治)膝关节腔内注射,每次2.5mL,每周一次,5周为一疗程。B组62个膝(双膝12例),治疗方法为第一周膝关节内注射玻璃酸钠(阿尔治)2.5mL后,再注入复方倍他米松1mL。以后四周继续玻璃酸钠(阿尔治)膝关节腔内注射,每周一次,每次2.5mL。A组和B组治疗疗程结束后2周,根据L equesne等的有关膝关节OA病情严重性指数评估方法,制定相应观察表。对第一次治疗前及第5次治疗结束后2周膝关节进行评分,分别对A、B两组治疗前后评分进行配对t检验,之后对A、B两组治疗后评分进行两样本均数比较的t检验。计算改善率。根据治疗前评分分别将A、B组患者分为轻中度和重度两组,根据改善率将疗效分为有效和无效。使用组内分组的卡方检验对上述计数资料进行检验。结果:80例病人全部得到回访。A、B两组治疗前评分无显著性差异(P>0.05),A组治疗后评分与治疗前评分有显著性差异(P<0.01),B组治疗后评分与治疗前评分也有显著性差异(P<0.01)。A、B两组治疗后评分无显著性差异(P>0.05)。A组显效13例(缓解率≥75%),有效31例(缓解率<75%,≥30%),无效3例(缓解率<30%);B组显效16例,有效43例,无效3例。结果显示A、B两组治疗效果无显著性差异(P>0.05)。玻璃酸钠组(A组)对膝关节骨关节炎病情轻中度和重度的病人疗效无显著性差异(P>0.05)。玻璃酸钠组联合复方倍他米松组(B组)同样对膝关节骨关节炎病情轻中度和重度的病人疗效无显著性差异(P>0.05)。结论:关节腔内注射玻璃酸钠及复方倍他米松联合玻璃酸钠关节腔内注射具有较好的、相同的临床效能。两种方法的短期疗效与病情轻重无关。     

骨肽关节内注射治疗膝骨性关节炎的疗效观察

目的探讨骨肽关节内注射治疗膝骨性关节炎的疗效。方法 5mL注射器抽取骨肽注射液20mg,选用髌骨外上缘穿刺点,缓慢注入骨肽,1周注射1次,连续4周。结果随访362例患者,男108例,女254例,年龄36～86岁,平均62.2岁,病史程0.5年～25年,平均12.8年,双膝68个,左膝189,右膝105,其中临床缓解242例(66.9%),有效87例(24%),无效33例(9.1%),总有效率90.9%。起效时间最短1d,最长1周。结论骨肽关节内注射治疗膝骨性关节炎,可以明显改善患者临床症状,提高生活质量。     

骨肽关节内注射治疗膝骨性关节炎的疗效观察

目的探讨骨肽关节内注射治疗膝骨性关节炎的疗效。方法 5mL注射器抽取骨肽注射液20mg,选用髌骨外上缘穿刺点,缓慢注入骨肽,1周注射1次,连续4周。结果随访362例患者,男108例,女254例,年龄36～86岁,平均62.2岁,病史程0.5～25年,平均12.8年,双膝68个,左膝189,右膝105,其中临床缓解242例(66.9%),有效87例(24%),无效33例(9.1%),总有效率90.9%。起效时间最短1d,最长1周。结论骨肽关节内注射治疗膝骨性关节炎,可以明显改善患者临床症状,提高生活质量。     

针刀联合关节腔内注射治疗膝骨性关节炎临床研究

目的：探讨针刀联合关节腔内注射治疗膝骨性关节炎临床疗效。方法256例膝骨性关节炎患者随机分成两组：A组予膝关节腔内注射治疗;B组予针刀联合膝关节腔内注射治疗。观察记录治疗前与治疗后两组VAS、HSS、主动关节活动度（AROM）变化。结果治疗后两组VAS评分均下降（P＜0.05）, B组下降更明显;两组HSS评分和AROM度数均高于治疗前（P＜0.05）, B组明显高于A组。结论针刀联合关节腔内注射治疗膝骨性关节炎疗效显著。     

In vitro evaluation and intra-articular administration of biodegradable microspheres containing naproxen sodium.

The dispersion of non-steroidal antiinflammatory drugs (NSAIDs) into biodegradable polymeric matrices have been accepted as a good approach for obtaining a therapeutic effect in a predetermined period of time meanwhile minimizing the side effects of NSAIDs. In the present study, it was aimed to prepare Naproxen Sodium (NS), (a NSAID) loaded microsphere formulation using natural Bovine Serum Albumin (BSA) and synthetic biodegradable polymers such as poly(lactide-co-glycolic acid) (PLGA) (50:50 MW 34,000 and 88,000 Da) for intra-articular administration, and to study the retention of the drug at the site of injection in the knee joint. NS incorporated microspheres were evaluated in vitro for particle size (the mean particle size; for BSA microspheres, 10.0 +/- 0.3 microm, for PLGA microspheres, 9.0 +/- 0.2 and 5.0 +/- 0.1 microm for MW 34,000 and 88,000 Da, respectively), yield value, drug loading, surface morphology and drug release. For in vivo studies, monoarticular arthritis was induced in the left knee joints of rabbits by using ovalbumin and Freund's Complete Adjuvant as antigen and adjuvant. A certain time (4 days) is allowed for the formation of arthritis in the knee joints, then the NS loaded microspheres were injected directly into the articular cavity. At specific time points, gamma scintigrams were obtained to determine the residence time of the microspheres in knee joints, in order to determine the most suitable formulation. This study indicated that PLGA, a synthetic polymer, is more promising than the natural type BSA microspheres for an effective cure of mono-articular arthritis in rabbits.     

Intra-articular therapy of experimental arthritis with a derivative of triamcinolone acetonide incorporated in liposomes

Abstract— Triamcinolone acetonide-21-palmitate was synthesized and incorporated into liposomes for intra-articular treatment of an experimentally-induced arthritis in the knee joints of rabbits. The liposomal formulation was more efficient than free triamcinolone acetonide in solution in suppressing the arthritis. Using radioactive tracers, it was found that triamcinolone acetonide-21-palmitate incorporated into liposomes was retained in the articular cavity, together with the liposomal lipids, for a much longer period than free triamcinolone acetonide, and this correlated with its anti-inflammatory effect.     

Treatment of Antigen-induced Arthritis in Rabbits with Liposome-entrapped Methotrexate Injected Intra-articularly

Abstract— Rabbits with a bilateral antigen-induced arthritis were injected intra-articularly in one joint with methotrexate as the free drug or entrapped in liposomes. Free methotrexate (1 mg) injected as a single dose at the time of antigen challenge, suppressed the development of joint swelling and the rise in skin surface temperature of treated joints by 20–30% compared with contralateral control arthritic joints. The beneficial effect of methotrexate occurred within 24 h of injection and was maintained for at least 56 days. However, methotrexate was ineffective in suppressing arthritis when injected 7 days after antigen challenge. Liposomal methotrexate suppressed the development of arthritis at a dose one-tenth that of the free drug and it was also effective in suppressing arthritis of 7 days duration, although significant beneficial effects of liposomal methotrexate were delayed for 10 to 14 days after injection. Neither free nor liposomal methotrexate was effective in suppressing an established arthritis, having no significant effect on joint swelling or skin surface temperature when injected 21 and 35 days after antigen challenge. At the end of the study, 8 or 9 weeks after induction of arthritis, the joints were examined morphologically and histologically. Free methotrexate generally had no significant effect on joint pathology. However, liposomal methotrexate suppressed the development of synovial hyperplasia, cellular infiltration and the erosion of cartilage and bone when injected at the time of antigen challenge or 7 days later, but affected none of these parameters in an established arthritis of 3 weeks duration.