Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders:a review of the literature

ABSTRACT

Background: There is a need for an effective treatment for the millions of people in the United States with osteoarthritis (OA), a degenerative joint disease. The demand for treatments, both traditional and non-traditional, will continue to grow as the population ages.

Scope: This article reviews the medical literature on the preclinical and clinical research on a unique compound, collagen hydrolysate. Articles were obtained through searches of the PubMed database (www.pubmed.gov) through May 2006 using several pairs of key words (collagen hydrolysate and osteoarthritis; collagen hydrolysate and cartilage; collagen hydrolysate and chondrocytes; collagen hydrolysate and clinical trial) without date limits. In addition, other sources of information, such as abstracts presented at scientific congresses and articles in the German medical literature not available on PubMed, were reviewed and included based on the authors’ judgment of their relevance to the topic of the review.

Findings: According to published research, orally administered collagen hydrolysate has been shown to be absorbed intestinally and to accumulate in cartilage. Collagen hydrolysate ingestion stimulates a statistically significant increase in synthesis of extracellular matrix macromolecules by chondrocytes (?p < 0.05 compared with untreated controls). These findings suggest mechanisms that might help patients affected by joint disorders such as OA. Four open-label and three double-blind studies were identified and reviewed; although many of these studies did not provide key information – such as the statistical significance of the findings – they showed collagen hydrolysate to be safe and to provide improvement in some measures of pain and function in some men and women with OA or other arthritic conditions.

Conclusion: A growing body of evidence provides a rationale for the use of collagen hydrolysate for patients with OA. It is hoped that ongoing and future research will clarify how collagen hydrolysate provides its clinical effects and determine which populations are most appropriate for treatment with this supplement.     

The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate

ABSTRACT

Background: Chondroitin sulfate has been shown to relieve pain and improve functional limitation in patients with osteoarthritis (OA) of the knee in numerous clinical trials and meta-analyses. Its role as a potential structure-modifying drug for knee OA, however, remains controversial.

Objective: To perform a meta-analysis of randomized double-blind placebo-controlled clinical trials to assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee OA.

Research design and methods: A Medline search was conducted from 1996 through 2007 and five articles that reported results from three trials were identified; one additional trial was identified through review of presentations at annual rheumatology meetings. There was no evidence of heterogeneity across the trials and results were pooled using a fixed effects meta-analysis.

Results: Pooled results demonstrated a small significant effect of chondroitin sulfate on the reduction in rate of decline in minimum joint space width of 0.07?mm/year (95% CI 0.03, 0.10) that corresponded to an effect size of 0.26 (95% CI 0.14, 0.38) (p?<?0.0001). This result was robust in sensitivity analyses.

Limitations: The individual studies included in the meta-analysis varied in the number of patients enrolled and the techniques used to acquire knee radiographs and to measure joint space width.

Conclusion: These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with OA of the knee. Chondroitin sulfate may have a role as a structure-modifying agent in the management of patients with knee OA.     

骨康保健贴治疗骨关节肌肉疼痛临床观察

目的探讨骨康保健贴治疗骨关节肌肉疼痛的疗效。方法将119例症见骨关节肌肉肿胀、疼痛、挛急、酸困不适、关节屈伸不利、功能障碍、或腰腿沉重,或腿臂间作痛等常见骨科疾病患者进行骨康保健贴外敷治疗。结果变态反应2例,其他原因停止治疗和随访失踪病例5例。治疗前后积分对比,显效36例占32.14%,有效65例占58.04%,无效11例占9.82%,总有效率为90.18%。结论骨康保健贴治疗骨关节肌肉疼痛有着显著的疗效。     

帕罗西汀治疗骨科慢性疼痛性疾病伴发抑郁的对照研究

目的探讨帕罗西汀治疗骨科慢性疼痛性疾病伴发抑郁的疗效和安全性。方法将80例骨科慢性疼痛性疾病伴发抑郁的患者随机分为治疗组和对照组，每组40例。治疗组给予帕罗西汀20mg／d，对照组给予安慰剂1片／d。分别于治疗第4周末评价临床总体疗效，并用汉密尔顿抑郁量表（HAMD）及不良反应症状量表（TESS）定量测评两组患者治疗前后的抑郁变化情况及用药后的不良反应。结果治疗组总有效率（痊愈率＋显著有效率＋有效率）和显效率（痊愈率＋显著有效率）分别达92．31％和64．10％，明显优于对照组。帕罗西汀主要的不良反应为短暂的轻至中度的恶心、食欲下降、头晕、困倦等。结论帕罗西汀用于治疗骨科慢性疼痛性疾病伴发抑郁疗效肯定，不良反应少，值得进一步研究和推广。     

临床药师参与一例晚期肿瘤患者疼痛治疗的案例分析

目的 临床药师参与癌痛患者止痛治疗,为患者提供药学服务,保障临床安全、合理用药。方法 根据癌症晚期患者疼痛治疗原则及疼痛特点,对患者进行疼痛评估、用药教育、药学监护,并分析可能存在的药物相互作用。结果 根据三阶梯治疗原则,通过全面评估患者疼痛,加用辅助药物协同镇痛,使患者疼痛得到有效控制。同时,临床药师在患者服药期间和减量过程中均进行用药指导,对药物不良反应进行监护,发现可能存在的药物相互作用,向临床医生提出合理建议并被采纳,使患者在有效镇痛的同时得到用药安全保障。结论 临床药师参与临床疼痛治疗,为患者提供药学服务,有效地协助临床医生用药,使用药更加安全,极大地提高了患者的满意度和生活质量。     

骨通贴膏治疗类风湿关节炎寒湿痹阻型临床疗效研究

目的 通过随机对照试验,观察骨通贴膏治疗类风湿关节炎（RA）寒湿痹阻型关节症状的疗效。方法 将140例RA患者随机分为空白组（n=40）、试验组（n=50）、对照组（n=50）,空白组维持原内服药治疗方案不变,不予其他治疗;试验组给予骨通贴膏外用每日1贴;对照组给予电热式蜡疗每日1次。记录并统计分析患者治疗前、治疗3 d、14 d后视觉模拟评分（VAS评分）、握力、晨僵时间、中医证候积分,治疗前及治疗14 d后类风湿因子（RF）、C反应蛋白（CRP）、血沉（ESR）情况。评价临床疗效,观察不良反应。结果 1治疗3 d后,试验组在VAS评分、晨僵时间、握力及中医证候积分上较治疗前有好转,差异有统计学意义（P < 0.05）。2周后,空白组各观察指标无明显变化（P > 0.05）,试验组、对照组在VAS评分、握力、晨僵时间（h）、中医证候积分、CRP、ESR上较治疗前均有改善（P < 0.05）;组间比较,试验组改善情况优于空白组及对照组（P < 0.05）,差异有统计学意义;治疗14 d后试验组RF轻度下降,但差异无统计学意义（P>0.05）。2试验组总有效率（94%）、临床控制率及显效率（控显率）83%均优于对照组总有效率（81%）、控显率（69%）,差异有统计学意义（P < 0.05）。3试验组及对照组各有2例轻微不良反应,均未退出试验。结论 骨通贴膏能有效缓解RA寒湿痹阻型小关节晨僵、疼痛、肿胀的临床症状,具有起效快、作用持久、携带及使用方便的优势,对类风湿关节炎患者临床疗效肯定。     

Prospective,non-interventional study on the tolerability and analgesic effectiveness over 12 weeks after a single application of capsaicin 8% cutaneous patch in 1044 patients with peripheral neuropathic pain: first results of the QUEPP study

Abstract

Background:

Reversible defunctionalisation of nociceptors by the TRPV1 agonist capsaicin in high concentration is an emerging new concept for the treatment of peripheral neuropathic pain.     

Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized,double-blind study*

ABSTRACT

Objective: Tapentadol is a novel, centrally acting analgesic with two mechanisms of action, μ-opioid receptor agonism and norepinephrine reuptake inhibition, in a single molecule. This phase III, randomized, double-blind, active-controlled study evaluated the tolerability of tapentadol immediate release (IR) and oxycodone IR for low back pain or osteoarthritis pain (hip or knee), using flexible dosing over 90 days.

Methods: Patients (N?=?878) were randomly assigned (4:1 ratio) to receive tapentadol IR (50 or 100?mg, q4-6h, p.o.) or oxycodone IR (10 or 15?mg, q4-6h, p.o.). Tapentadol IR was evaluated for tolerability over 90 days, tolerability relative to oxycodone IR, withdrawal symptoms, and pain intensity. This study was not placebo-controlled, which limited efficacy evaluations.

Results: In total, 849 intent-to-treat patients received tapentadol IR (n?=?679) or oxycodone IR (n?=?170), and among these, 391 patients (57.6%) in the tapentadol IR group and 86 patients (50.6%) in the oxycodone IR group completed the study. Gastrointestinal events, including nausea (18.4% vs 29.4%), vomiting (16.9% vs 30.0%), and constipation (12.8% vs 27.1%), were reported by 44.2% of patients receiving tapentadol IR and 63.5% of patients receiving oxycodone IR, respectively. Nervous system events, including dizziness (18.1% vs 17.1%), headache (11.5% vs 10.0%), and somnolence (10.2% vs 9.4%), were reported by 36.7% of patients receiving tapentadol and 37.1% of patients receiving oxycodone, respectively. Odds ratios (tapentadol:oxycodone) showed that the incidences of somnolence and dizziness were similar; however, nausea, vomiting, and constipation were significantly less likely with tapentadol IR compared with oxycodone IR. The pattern of withdrawal symptoms suggests that drug tapering may not be necessary after tapentadol IR treatment of this duration. Pain intensity measurements showed similar efficacy for tapentadol and oxycodone.

Conclusion: During this 90-day study, tapentadol IR was associated with improved gastrointestinal tolerability compared with oxycodone IR while providing similar pain relief.

Trial registration information: NCT00364546.     

Synthesis of a novel polyamidoamine dendrimer conjugating with alkali blue as a lymphatic tracer and study on the lymphatic targeting in vivo

In this study, a novel lymphatic tracer polyamidoamin-alkali blue (PAMAM-AB) was synthesized in order to evaluate the intra-lymphatic targeting ability and lymphatic tropism of PAMAM-AB after subcutaneous administration. UV-Vis, FT-IR, NMR and HPLC characterization were performed to prove the successful synthesis of PAMAM-AB. The calculated AB payload of PAMAM-AB conjugate was seven per dendrimer molecule (27.16% by weight). Hydrolysis stability of PAMAM-AB in vitro was evaluated, which was stable in PBS and human plasma. Lymphatic tracing were studied to determine the blue-stained intensity of PAMAM-AB in right popliteral lymph nodes (PLNs), iliac lymph nodes (ILNs) and para-aortic lymph nodes (PALNs) after subcutaneous administration. The pharmacokinetics and biodistribution of PAMAM-AB in mice were investigated. PLNs, ILNs and PALNs could be obviously blue-stained within 10?min after PAMAM-AB administration, and displayed a more rapid lymphatic absorption, a higher AUC value in lymph nodes and a longer lymph nodes residence time compared with methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), MB multiple microemulsion (MB-MME). Enhanced lymphatic drainage from the injection site and uptake into lymph of PAMAM-AB indicated that PAMAM-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors or as a lymphatic tracer in its own right.