BACKGROUND Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease,but its pathogenesis is not fully understood,and its clinical treatment has limitations.Glucosamine sulfate capsules are co...BACKGROUND Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease,but its pathogenesis is not fully understood,and its clinical treatment has limitations.Glucosamine sulfate capsules are commonly used for treating arthritis,and San Bi Tang is a classic formula of traditional Chinese medicine(TCM)that has the effects of warming yang,dispelling dampness,relaxing muscles,and activating collaterals.This research hypothesized that the combination of modified San Bi Tang and glucosamine sulfate capsules could enhance the clinical efficacy of treating cold-dampness-type knee osteoarthritis through complementary effects.AIM To analyze the clinical efficacy of San Bi Tang combined with glucosamine sulfate capsules when treating cold-dampness-type knee osteoarthritis.METHODS A total of 110 patients with cold-dampness-type knee osteoarthritis were selected as research subjects and randomly divided into a control group and an experimental group of 55 cases each.The control group received only treatment with glucosamine sulfate capsules,while the experimental group received additional treatment with modified San Bi Tang for a duration of 5 wk.The patients’knee joint functions,liver and kidney function indicators,adverse reactions,and vital signs were evaluated and analyzed using SPSS 26.0 software.RESULTS Before treatment,the two groups’genders,ages,and scores were not significantly different,indicating comparability.Both groups’scores improved after treatment,which could indicate pain and knee joint function improvement,but the test group had better scores.The TCM-specific symptoms and the clinical efficacy of the treatment in the test group were higher.Before and after treatment,there were no abnormalities in the patients’liver and kidney function indicators.CONCLUSION The combination of modified San Bi Tang and glucosamine sulfate capsules is superior to treatment with sulfated glucosamine alone and has high safety.展开更多
BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clin...BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.展开更多
Glucosamine sulfate is a natural constituent of cartilage and is used in the treatment of knee osteoarthritis. The aim of this study is to provide a short but comprehensive pharmacotherapeutic update on treating knee ...Glucosamine sulfate is a natural constituent of cartilage and is used in the treatment of knee osteoarthritis. The aim of this study is to provide a short but comprehensive pharmacotherapeutic update on treating knee osteoarthritis with glucosamine sulfate. A literature search was conducted of PubMed, Centre for Reviews and Dissemination databases, Cochrane Reviews and EconLit up to January 2010. The literature review indicated that the mechanism of action of glucosamine sulfate is based on hypothesis, but its treatment effects in knee osteoarthritis are symptomatic. With steady-state peak concentrations at the 1,500 mg dosage in the range of 10 µM, it is estimated that only 2% of glucosamine is incorporated in the cartilage. A once-daily dosage of 1,500 mg of glucosamine sulfate is licensed for the treatment of symptomatic osteoarthritis and has been shown to reduce pain, improve function and exhibit similar safety to placebo. Glucosamine sulfate is likely to be a cost-effective treatment of knee osteoarthritis. In conclusion, a once-daily dosage of 1,500 mg of glucosamine sulfate is likely to be a safe, effective and cost-effective treatment of knee osteoarthritis as compared to placebo.展开更多
Objective: This study aims to show that a proprietary topical cream can deliver glucosamine through the skin into the synovial fluid of osteoarthritic patients. This cream contains 10% w/w glucosamine sulfate. It also...Objective: This study aims to show that a proprietary topical cream can deliver glucosamine through the skin into the synovial fluid of osteoarthritic patients. This cream contains 10% w/w glucosamine sulfate. It also aims to determine the endogenous level of glucosamine in the synovial fluid of these patients. Therapeutic effectiveness of glucosamine is not addressed in this study. Design: This phase IV, open-label, nonrandomized study enrolled 240 patients. Participants from the Test group received a single dose treatment (2 g of cream), and synovial fluid samples were collected 1 - 3 hours post-treatment. Patients from the Control group were not subjected to any treatment but their synovial fluid was also sampled to establish a glucosamine concentration baseline for Time-0 (T0). Glucosamine concentrations were determined by HPLC analysis. Results: The mean glucosamine concentration in the synovial fluid of patients from the Test group (100.56 ng/ml, 95% CI 66.36 - 134.76, n = 117) was higher than in the Control group (17.83 ng/ml, 95% CI 7.42 - 28.24, n = 117) resulting in a significant between-group difference (p Conclusion: The results suggest that glucosamine can be topically delivered across the human skin into the synovial fluid using a proper vehicle. This suggests that other water-soluble molecules could similarly be delivered transdermally, alleviating the need for oral delivery in cases where oral administration is difficult, or when harmful side effects could ensue.展开更多
The double salt of glucosamine sulfate sodium chloride(glucosamine-SP) is an important pharmaceuticals ingredient for healing osteoarthritis. However, the study about its industrial production is rarely documented, le...The double salt of glucosamine sulfate sodium chloride(glucosamine-SP) is an important pharmaceuticals ingredient for healing osteoarthritis. However, the study about its industrial production is rarely documented, let alone the optimization over the whole process to produce glucosamine-SP using glucosamine hydrochloride and anhydrous sodium sulfate as synthetic raw materials. In order to improve the production efficiency, this study screened the process parameters based on the concept of quality by design(QbD), optimized 13 operational parameters related to reaction and separation in the process, and finally proposed the mixed dropping process. The reaction conditions for the preparation of glucosamineSP were found as follows: the molar ratio of anhydrous sodium sulfate to glucosamine hydrochloride is 0.42, the mass ratio of water to glucosamine hydrochloride is is 2.0, the reaction temperature is 50 ℃ and the reaction time is 1 h. Through step-by-step scaling up following QbD, the mixed dropping process was successfully applied to achieve a trial production of 200 kg products satisfying national quality standards.In all, the results of this study have high technical value and guiding significance for the industrial mass production of glucosamine-SP.展开更多
[Objectives]This study was conducted to optimize the Formulation Process of glucosamine chondroitin sulfate tablets. [Methods] The orthogonal design with three levels was carried out with microcrystalline cellulose, c...[Objectives]This study was conducted to optimize the Formulation Process of glucosamine chondroitin sulfate tablets. [Methods] The orthogonal design with three levels was carried out with microcrystalline cellulose, calcium hydrophosphate and cross-linked polyvinylpyrrolidone as three factors to optimize the preparation process. [Results] When microcrystalline cellulose 200 mg/tablet, calcium hydrophosphate 150 mg/tablet, and cross-linked polyvinylpyrrolidone 80 mg/tablet were added, the angle of repose could meet the requirements of tablet pressing, and the dissolution could reach more than 95% in 30 min. The results of the orthogonal test showed that the dissolution effect of self-made tablets was faster than that of commercial products. [Conclusions] The glucosamine hydrochloride chondroitin sulfate tablets prepared by this prescription have better quality.展开更多
The prevalence of primary or idiopathic osteoarthritis(OA) of knee and hip joints has substantially increased in general population during the last decades. Analgesics and non-steroidal anti-inflammatory drugs are cur...The prevalence of primary or idiopathic osteoarthritis(OA) of knee and hip joints has substantially increased in general population during the last decades. Analgesics and non-steroidal anti-inflammatory drugs are currently extensively used as non-surgical treatmentoptions. However, they act as symptomatic treatments, not offering a cure of OA and they are accused for an increased risk of adverse events. Glucosamine(GL) and chondroitin(CH) are nutritional supplements that have recently gained widespread use as treatment options for OA. They potentially or theoretically act as chondroprotectors or/and as "disease-modifying OA drugs" offering not only symptomatic relief but also alteration of the natural history of OA. However, although many studies have showed a significant treatment effect, accompanied with remarkable safety, there is still controversy regarding their relative effectiveness compared with placebo or other treatments. The scope of this review is to present and critically evaluate the current evidence-based information regarding the administration of GL and CH for the treatment of knee or hip OA. Our focus is to investigate the clinical efficacy and safety after the use of these supplements. An effect of GL and CH on both clinical and radiological findings has been shown. However, only a few high-quality level I trials exist in the literature, especially on the assessment of radiological progression of OA. The effect sizes are generally small and probably not clinically relevant. Even the validity of these results is limited by the high risk of bias introduced in the studies. Both GL and CH seem to be safe with no serious adverse events reported. There is currently no convincing information for the efficacy of GL and CH on OA.展开更多
Glucosamine and chondroitin sulfate are molecules involved in the formation of articular cartilage and are frequently used for symptom relief in patients with arthrosis.These molecules are well tolerated with scarce s...Glucosamine and chondroitin sulfate are molecules involved in the formation of articular cartilage and are frequently used for symptom relief in patients with arthrosis.These molecules are well tolerated with scarce secondary effects.Very few cases of possible hepatotoxicity due to these substances have been described.The aim of this paper is to report the frequency of presumed glucosamine hepatotoxicity in patients with liver disease.A questionnaire was given to 151 consecutive patients with chronic liver disease of different etiology(mean age 59 years,56.9%women)attended in an outpatient clinic with the aim of evaluating the frequency of consumption of these drugs and determine whether their use coincided with a worsening in liver function test results.Twenty-three patients(15.2%)recognized having taken products containing glucosamine or chondroitin sulfate previously or at the time of the questionnaire.Review of the clinical records and liver function tests identified 2 patients presenting an elevation in aminotransferase values temporarily associated with glucosamine treatment;one of the cases simultaneously presented a skin rash attributed to the drug.Review of these two patients and the cases described in the literature suggest toxicity of glucosamine and chondroitin sulfate.The clinical spectrum is variable,and the mechanism of toxicity is not clear but may involve reactions of hypersensitivity.The consumption of products containing glucosamine and/or chondroitin sulfate is frequent among patients with chronic liver diseases and should be taken into account on the appearance of alterations in liver function tests not explained by the underlying disease.展开更多
Glucosamine sulfate was prepared from glucosamine hydrochloride that was produced by acidic hydrolysis of chitin by ion-exchange method. Optical rotation and elemental analysis characterized the degree of its purity. ...Glucosamine sulfate was prepared from glucosamine hydrochloride that was produced by acidic hydrolysis of chitin by ion-exchange method. Optical rotation and elemental analysis characterized the degree of its purity. In addition, the antioxidant potency of cbitosan derivative-glucosamine sulfate was investigated in various established in vitro systems, such as superoxide (O2^-)/hydroxyl (·OH) radicals scavenging, reducing power, iron ion chelating. The following results are obtained: first, glucosamine sulfate had pronounced scavenging effect on superoxide radical. For example the O2 scavenging activity of glucosamine sulfate was 92.11% at 0.8 mg/mL. Second, the ·OH scavenging activity of glucosamine sulfate was also strong, and was about 50% at 3.2 mg/mL. Third, the reducing power of glucosamine sulfate was more pronounced. The reducing power of glucosamine sulfate was 0.643 at 0.75 mg/mL. However, its potency for ferrous ion chelating was weak. Furthermore, except for ferrous ion chelating potency, the scavenging rate of radical and reducing power of glucosamine sulfate were concentration-dependent and increased with their increasing concentrations, but its ferrous ion chelating potency decreased with the increasing concentration. The multiple antioxidant activities of glucosamine sulfate were evidents of reducing power and superoxide/hydroxyl radicals scavenging ability. These in vitro results suggest the possibility that glucosamine sulfate could be used effectively as an ingredient in health or functional food, to alleviate oxidative stress.展开更多
Based upon a series of research studies, scientific organizations considered Glucosamine and Chondroitin “not appropriate” as osteoarthritis (OA) of the knee modifying drugs and uncertain as pain relievers. Research...Based upon a series of research studies, scientific organizations considered Glucosamine and Chondroitin “not appropriate” as osteoarthritis (OA) of the knee modifying drugs and uncertain as pain relievers. Research studies which served as foundation for the aforementioned conclusions focused on the oral use of the substances. On the other hand, studies recommend that topical administration in treating OA be considered first line therapy, since it is said to be advantageous for its efficacy in treating localized situations, as it allows greater local concentration and it results in smaller systemic effects. Studies found did not provide sufficient evidence for good development and application strategies and were not enough to prove the technique to be effective or non-effective. Several other aspects must be clarified. In order to enhance permeation and delivery of Glucosamine and Chondroitin to knee joint, combining the advantages of intravenous infusion therapy with the convenience of oral administration, the suggested course of action is to transform skin delivery technology, while clarifying other points discussed throughout this research study.展开更多
[Objectives] To observe the clinical effects of activating blood circulation to resolve blood stasis and glucosamine hydrochloride capsules therapy on post-traumatic knee osteoarthritis treatment,to measure the expres...[Objectives] To observe the clinical effects of activating blood circulation to resolve blood stasis and glucosamine hydrochloride capsules therapy on post-traumatic knee osteoarthritis treatment,to measure the expression of matrix metalloproteinase in post-traumatic knee osteoarthritis patients before and after treatment,and to explore its relevant molecular mechanisms. [Methods]A total of 60 patients with posttraumatic knee osteoarthritis in early stage in Affiliated Hospital of Shannxi University of Chinese Medicine from January 2015 to December2017 were selected and randomly divided into the control group( n = 30) and the observation group( n = 30). The control group was given oral administration of glucosamine hydrochloride capsules for 6 courses of the treatment. The observation group was using the activating blood circulation to resolve blood stasis therapy for 6 courses of treatment. The recovery of traumatic knee osteoarthritis and the symptom of traditional Chinese medicine( TCM) in 2 groups was compared before and after treatment. The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and the TCM symptom scores were recorded in both groups. And the synovial fluid and serum of patients were collected to detect the expression of matrix metalloproteinase. [Results]The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and TCM symptom scores of the 2 groups in the 1 st week,the 12 th week and the 24 th week after the treatment were significantly lower than those before the treatment,and the difference was statistically significant( P < 0. 05). Two therapeutic methods had certain therapeutic effects on the recovery from traumatic knee osteoarthritis,and could significantly improve the TCM syndrome. There were better therapeutic effects on oral decoction of traditional Chinese medicine than oral glycosaminoglycans hydrochloride capsules on treating traumatic knee osteogenesis( P < 0. 05). The expression level of MMP3 was decreased significantly in both groups( P <0. 001),while the expression level of MMP13 had no significant change in both groups( P >0. 05). The expression level of MMP1 was decreased significantly in the observation group( P < 0. 001),but there was no significant change in the control group after treatment( P >0. 05). [Conclusions]Two treatment methods have been effective in this clinical study. We found that the expression level of MMP3 was decreased significantly after treatment in 2 therapies,which can be clinically applied.展开更多
Osteoarthritis (OA) is a chronic, painful disease affecting articulating joints in man and animals. It is characterized by cartilage breakdown, bone remodeling, osteophyte formation and joint inflammation. Currently u...Osteoarthritis (OA) is a chronic, painful disease affecting articulating joints in man and animals. It is characterized by cartilage breakdown, bone remodeling, osteophyte formation and joint inflammation. Currently used non-steroidal anti-inflammatory drugs for the management of OA are known to have deleterious side effects. To address the need for alternatives, we evaluated the anti-inflammatory effects of a combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU) and chondroitin sulfate (CS) by measuring chemokine MCP-1 (monocyte chemoattractant protein 1, CCL2) and prostaglandin E-2 (PGE2) in stimulated chondrocytes. As the only cellular constituents of cartilage, chondrocytes are the source of pro-inflammatory mediators that play critical roles in the pathogenesis of OA. Chondrocytes were incubated: with: 1) control media, 2) [ASU + GLU + CS] combination, or 3) Phenylbutazone (PBZ) for 24 hours. Cells were next stimulated with IL-1β or LPS for another 24 hrs. MCP-1 and PGE2 from supernatants were quantitated by immunoassay. Another set of chondrocytes seeded in chamber slides were stimulated with IL-1β for 1 hour and then immunostained for NF-κB. Chondrocytes stimulated with IL-1β or LPS significantly increased MCP-1 and PGE2 production which were significantly reduced after treatment with [ASU + GLU + CS]. In contrast, PBZ significantly reduced PGE2 but not MCP-1 production. IL-1β stimulation induced nuclear translocation of NF-κB, which was inhibited by pre-treatment with either [ASU + GLU + CS] or PBZ. The present study provides evidence that the production of MCP-1 by chondrocytes can be inhibited by the combination of [ASU + GLU + CS] but not by PBZ. In contrast, PGE2 production was inhibited by either treatment suggesting that the production of MCP-1 and PGE2 could be independently regulated. The finding of distinct effects of [ASU + GLU + CS] on MCP-1 and PGE2 synthesis supports a scientific rationale for a multimodal treatment approach in the management of OA.展开更多
Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage.Traditional treatments for OA are limited to alleviating various OA symptoms.There is a lack of ...Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage.Traditional treatments for OA are limited to alleviating various OA symptoms.There is a lack of drugs available in clinical practice that can truly repair cartilage damage.Here,we developed the chondroitin sulfate analog CS-semi5,semi-synthesized from chondroitin sulfate A.In vivo,CS-semi5 alleviated inflammation,provided analgesic effects,and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model.A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats,revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment.Binding prediction revealed that miR-122-5p acted on the 30-untranslated region of p38 mitogen-activated protein kinase,which was related to MMP13 regulation.Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis,which was further validated in the articular cartilage of OA rats.This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5,revealing its cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.展开更多
The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoartbritis was induced in rats after sin...The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoartbritis was induced in rats after single intra-articular injection of sodium iodoacetate. Rats were sacrificed 1, 2, 4, and 8 weeks post intra-articular injection to evaluate the progression of histopathogenesis of osteoarthritis. Diacerein was orally administered (15 mg/kg) once daily post 1 and 2 weeks of iodoacetate injection in two groups, respectively, for up to 12 weeks. Articular cartilage and sub- chondral bone of the rats of both groups were examined after 8 and 12 weeks, respectively. Quantitative histological analyses were performed by scoring these sections as per the OARSI system. Chondroitin sulfate was also estimated in articular cartilage by decrease in absorbance of methylene blue on complexation with chondroitin sulfate using a spectrophotometer. Intra-articular injection of iodoacetate induced loss of articular cartilage with progressive sub- chondral bone sclerosis and degeneration. Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect. Furthermore, the chondroprotective effect of diacerein was found to be more pro- nounced after 12 weeks as compared to 8 weeks in both cases (i.e., post 1 and 2 weeks of iodoacetate injection). Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chon- droprotective effect. In conclusion, diacerein exhibits chondroprotective effect in rats with late onset of action.展开更多
Glucosamine,referred to as Glc N,is a product in which one hydroxyl group of glucose is replaced by one amino group. Glc N is widely present in plants,animals and microorganisms. After research,ammonia sugar has a goo...Glucosamine,referred to as Glc N,is a product in which one hydroxyl group of glucose is replaced by one amino group. Glc N is widely present in plants,animals and microorganisms. After research,ammonia sugar has a good effect on the treatment of osteoarthritis,the suppression of cancer,and the recovery of cognitive impairment caused by hypoxia in some animals. This article summarized the application of Glc N in the medical field,and lays a foundation for the further development of Glc N in the field of biomedicine.展开更多
Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters ove...Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters over-expressed reactive oxygen species(ROS),extracellular matrix disintegration,and apoptosis of chondrocytes.In this study,a kind of ROS-scavenging,biodegradable and drug-free nanoparticles(PP NPs)were constructed by the crosslinking of poly(propylene fumarate)(PPF)and ROS-scavenging poly(thioketal)(PTK).The high content of PTK and high crosslinking density of PPF and PTK innovatively endowed the NPs with slow degradation and prolonged ROS-elimination ability.The NPs were further surface-modified with chondroitin sulfate(CS),one of the dietary supplements for osteoarthritis.The intrinsic properties of resultant PP-CS NPs were excavated in vitro and in vivo.The PP-CS NPs could desirably consume 1,10-diphenyl-2-picrylhydrazyl(DPPH)radicals without toxicity to RAW264.7 cells in vitro.With an average diameter of~300 nm,the PP-CS NPs could be intra-articular administrated in OA rats and showed prolonged joint retention time,allowing only one injection per month.Moreover,the PP-CS NPs possessed a prolonged ROS depletion and M2 macrophage induction effect,down-regulated inflammatory cytokines,and reduced glycosaminoglycans loss.Consequently,the PP-CS NPs protected articular surface erosion,inhibited uneven cartilage matrix,and attenuated OA progression.展开更多
文摘BACKGROUND Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease,but its pathogenesis is not fully understood,and its clinical treatment has limitations.Glucosamine sulfate capsules are commonly used for treating arthritis,and San Bi Tang is a classic formula of traditional Chinese medicine(TCM)that has the effects of warming yang,dispelling dampness,relaxing muscles,and activating collaterals.This research hypothesized that the combination of modified San Bi Tang and glucosamine sulfate capsules could enhance the clinical efficacy of treating cold-dampness-type knee osteoarthritis through complementary effects.AIM To analyze the clinical efficacy of San Bi Tang combined with glucosamine sulfate capsules when treating cold-dampness-type knee osteoarthritis.METHODS A total of 110 patients with cold-dampness-type knee osteoarthritis were selected as research subjects and randomly divided into a control group and an experimental group of 55 cases each.The control group received only treatment with glucosamine sulfate capsules,while the experimental group received additional treatment with modified San Bi Tang for a duration of 5 wk.The patients’knee joint functions,liver and kidney function indicators,adverse reactions,and vital signs were evaluated and analyzed using SPSS 26.0 software.RESULTS Before treatment,the two groups’genders,ages,and scores were not significantly different,indicating comparability.Both groups’scores improved after treatment,which could indicate pain and knee joint function improvement,but the test group had better scores.The TCM-specific symptoms and the clinical efficacy of the treatment in the test group were higher.Before and after treatment,there were no abnormalities in the patients’liver and kidney function indicators.CONCLUSION The combination of modified San Bi Tang and glucosamine sulfate capsules is superior to treatment with sulfated glucosamine alone and has high safety.
文摘BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.
文摘Glucosamine sulfate is a natural constituent of cartilage and is used in the treatment of knee osteoarthritis. The aim of this study is to provide a short but comprehensive pharmacotherapeutic update on treating knee osteoarthritis with glucosamine sulfate. A literature search was conducted of PubMed, Centre for Reviews and Dissemination databases, Cochrane Reviews and EconLit up to January 2010. The literature review indicated that the mechanism of action of glucosamine sulfate is based on hypothesis, but its treatment effects in knee osteoarthritis are symptomatic. With steady-state peak concentrations at the 1,500 mg dosage in the range of 10 µM, it is estimated that only 2% of glucosamine is incorporated in the cartilage. A once-daily dosage of 1,500 mg of glucosamine sulfate is licensed for the treatment of symptomatic osteoarthritis and has been shown to reduce pain, improve function and exhibit similar safety to placebo. Glucosamine sulfate is likely to be a cost-effective treatment of knee osteoarthritis. In conclusion, a once-daily dosage of 1,500 mg of glucosamine sulfate is likely to be a safe, effective and cost-effective treatment of knee osteoarthritis as compared to placebo.
文摘Objective: This study aims to show that a proprietary topical cream can deliver glucosamine through the skin into the synovial fluid of osteoarthritic patients. This cream contains 10% w/w glucosamine sulfate. It also aims to determine the endogenous level of glucosamine in the synovial fluid of these patients. Therapeutic effectiveness of glucosamine is not addressed in this study. Design: This phase IV, open-label, nonrandomized study enrolled 240 patients. Participants from the Test group received a single dose treatment (2 g of cream), and synovial fluid samples were collected 1 - 3 hours post-treatment. Patients from the Control group were not subjected to any treatment but their synovial fluid was also sampled to establish a glucosamine concentration baseline for Time-0 (T0). Glucosamine concentrations were determined by HPLC analysis. Results: The mean glucosamine concentration in the synovial fluid of patients from the Test group (100.56 ng/ml, 95% CI 66.36 - 134.76, n = 117) was higher than in the Control group (17.83 ng/ml, 95% CI 7.42 - 28.24, n = 117) resulting in a significant between-group difference (p Conclusion: The results suggest that glucosamine can be topically delivered across the human skin into the synovial fluid using a proper vehicle. This suggests that other water-soluble molecules could similarly be delivered transdermally, alleviating the need for oral delivery in cases where oral administration is difficult, or when harmful side effects could ensue.
基金supported by the Science and Technology Program of Xiamen, China (No. 3502Z20173018)。
文摘The double salt of glucosamine sulfate sodium chloride(glucosamine-SP) is an important pharmaceuticals ingredient for healing osteoarthritis. However, the study about its industrial production is rarely documented, let alone the optimization over the whole process to produce glucosamine-SP using glucosamine hydrochloride and anhydrous sodium sulfate as synthetic raw materials. In order to improve the production efficiency, this study screened the process parameters based on the concept of quality by design(QbD), optimized 13 operational parameters related to reaction and separation in the process, and finally proposed the mixed dropping process. The reaction conditions for the preparation of glucosamineSP were found as follows: the molar ratio of anhydrous sodium sulfate to glucosamine hydrochloride is 0.42, the mass ratio of water to glucosamine hydrochloride is is 2.0, the reaction temperature is 50 ℃ and the reaction time is 1 h. Through step-by-step scaling up following QbD, the mixed dropping process was successfully applied to achieve a trial production of 200 kg products satisfying national quality standards.In all, the results of this study have high technical value and guiding significance for the industrial mass production of glucosamine-SP.
基金Supported by School-level High-level Talent Project (XGY2021A022)Doctoral Research Startup Fund of Department of Science&Technology of Liaoning Province (2021-BS-252)。
文摘[Objectives]This study was conducted to optimize the Formulation Process of glucosamine chondroitin sulfate tablets. [Methods] The orthogonal design with three levels was carried out with microcrystalline cellulose, calcium hydrophosphate and cross-linked polyvinylpyrrolidone as three factors to optimize the preparation process. [Results] When microcrystalline cellulose 200 mg/tablet, calcium hydrophosphate 150 mg/tablet, and cross-linked polyvinylpyrrolidone 80 mg/tablet were added, the angle of repose could meet the requirements of tablet pressing, and the dissolution could reach more than 95% in 30 min. The results of the orthogonal test showed that the dissolution effect of self-made tablets was faster than that of commercial products. [Conclusions] The glucosamine hydrochloride chondroitin sulfate tablets prepared by this prescription have better quality.
文摘The prevalence of primary or idiopathic osteoarthritis(OA) of knee and hip joints has substantially increased in general population during the last decades. Analgesics and non-steroidal anti-inflammatory drugs are currently extensively used as non-surgical treatmentoptions. However, they act as symptomatic treatments, not offering a cure of OA and they are accused for an increased risk of adverse events. Glucosamine(GL) and chondroitin(CH) are nutritional supplements that have recently gained widespread use as treatment options for OA. They potentially or theoretically act as chondroprotectors or/and as "disease-modifying OA drugs" offering not only symptomatic relief but also alteration of the natural history of OA. However, although many studies have showed a significant treatment effect, accompanied with remarkable safety, there is still controversy regarding their relative effectiveness compared with placebo or other treatments. The scope of this review is to present and critically evaluate the current evidence-based information regarding the administration of GL and CH for the treatment of knee or hip OA. Our focus is to investigate the clinical efficacy and safety after the use of these supplements. An effect of GL and CH on both clinical and radiological findings has been shown. However, only a few high-quality level I trials exist in the literature, especially on the assessment of radiological progression of OA. The effect sizes are generally small and probably not clinically relevant. Even the validity of these results is limited by the high risk of bias introduced in the studies. Both GL and CH seem to be safe with no serious adverse events reported. There is currently no convincing information for the efficacy of GL and CH on OA.
文摘Glucosamine and chondroitin sulfate are molecules involved in the formation of articular cartilage and are frequently used for symptom relief in patients with arthrosis.These molecules are well tolerated with scarce secondary effects.Very few cases of possible hepatotoxicity due to these substances have been described.The aim of this paper is to report the frequency of presumed glucosamine hepatotoxicity in patients with liver disease.A questionnaire was given to 151 consecutive patients with chronic liver disease of different etiology(mean age 59 years,56.9%women)attended in an outpatient clinic with the aim of evaluating the frequency of consumption of these drugs and determine whether their use coincided with a worsening in liver function test results.Twenty-three patients(15.2%)recognized having taken products containing glucosamine or chondroitin sulfate previously or at the time of the questionnaire.Review of the clinical records and liver function tests identified 2 patients presenting an elevation in aminotransferase values temporarily associated with glucosamine treatment;one of the cases simultaneously presented a skin rash attributed to the drug.Review of these two patients and the cases described in the literature suggest toxicity of glucosamine and chondroitin sulfate.The clinical spectrum is variable,and the mechanism of toxicity is not clear but may involve reactions of hypersensitivity.The consumption of products containing glucosamine and/or chondroitin sulfate is frequent among patients with chronic liver diseases and should be taken into account on the appearance of alterations in liver function tests not explained by the underlying disease.
基金Supported by the Talent Program of Chinese Academy of Sciences (Dongbei Zhi Chun)Award Foundation of Scientific Research for Excellent Young and Middle-Age Scientist of Shandong Province (No. 2007BS07002)
文摘Glucosamine sulfate was prepared from glucosamine hydrochloride that was produced by acidic hydrolysis of chitin by ion-exchange method. Optical rotation and elemental analysis characterized the degree of its purity. In addition, the antioxidant potency of cbitosan derivative-glucosamine sulfate was investigated in various established in vitro systems, such as superoxide (O2^-)/hydroxyl (·OH) radicals scavenging, reducing power, iron ion chelating. The following results are obtained: first, glucosamine sulfate had pronounced scavenging effect on superoxide radical. For example the O2 scavenging activity of glucosamine sulfate was 92.11% at 0.8 mg/mL. Second, the ·OH scavenging activity of glucosamine sulfate was also strong, and was about 50% at 3.2 mg/mL. Third, the reducing power of glucosamine sulfate was more pronounced. The reducing power of glucosamine sulfate was 0.643 at 0.75 mg/mL. However, its potency for ferrous ion chelating was weak. Furthermore, except for ferrous ion chelating potency, the scavenging rate of radical and reducing power of glucosamine sulfate were concentration-dependent and increased with their increasing concentrations, but its ferrous ion chelating potency decreased with the increasing concentration. The multiple antioxidant activities of glucosamine sulfate were evidents of reducing power and superoxide/hydroxyl radicals scavenging ability. These in vitro results suggest the possibility that glucosamine sulfate could be used effectively as an ingredient in health or functional food, to alleviate oxidative stress.
文摘Based upon a series of research studies, scientific organizations considered Glucosamine and Chondroitin “not appropriate” as osteoarthritis (OA) of the knee modifying drugs and uncertain as pain relievers. Research studies which served as foundation for the aforementioned conclusions focused on the oral use of the substances. On the other hand, studies recommend that topical administration in treating OA be considered first line therapy, since it is said to be advantageous for its efficacy in treating localized situations, as it allows greater local concentration and it results in smaller systemic effects. Studies found did not provide sufficient evidence for good development and application strategies and were not enough to prove the technique to be effective or non-effective. Several other aspects must be clarified. In order to enhance permeation and delivery of Glucosamine and Chondroitin to knee joint, combining the advantages of intravenous infusion therapy with the convenience of oral administration, the suggested course of action is to transform skin delivery technology, while clarifying other points discussed throughout this research study.
基金Supported by Shaanxi Administration of Traditional Chinese Medicine(LCPT034)
文摘[Objectives] To observe the clinical effects of activating blood circulation to resolve blood stasis and glucosamine hydrochloride capsules therapy on post-traumatic knee osteoarthritis treatment,to measure the expression of matrix metalloproteinase in post-traumatic knee osteoarthritis patients before and after treatment,and to explore its relevant molecular mechanisms. [Methods]A total of 60 patients with posttraumatic knee osteoarthritis in early stage in Affiliated Hospital of Shannxi University of Chinese Medicine from January 2015 to December2017 were selected and randomly divided into the control group( n = 30) and the observation group( n = 30). The control group was given oral administration of glucosamine hydrochloride capsules for 6 courses of the treatment. The observation group was using the activating blood circulation to resolve blood stasis therapy for 6 courses of treatment. The recovery of traumatic knee osteoarthritis and the symptom of traditional Chinese medicine( TCM) in 2 groups was compared before and after treatment. The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and the TCM symptom scores were recorded in both groups. And the synovial fluid and serum of patients were collected to detect the expression of matrix metalloproteinase. [Results]The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and TCM symptom scores of the 2 groups in the 1 st week,the 12 th week and the 24 th week after the treatment were significantly lower than those before the treatment,and the difference was statistically significant( P < 0. 05). Two therapeutic methods had certain therapeutic effects on the recovery from traumatic knee osteoarthritis,and could significantly improve the TCM syndrome. There were better therapeutic effects on oral decoction of traditional Chinese medicine than oral glycosaminoglycans hydrochloride capsules on treating traumatic knee osteogenesis( P < 0. 05). The expression level of MMP3 was decreased significantly in both groups( P <0. 001),while the expression level of MMP13 had no significant change in both groups( P >0. 05). The expression level of MMP1 was decreased significantly in the observation group( P < 0. 001),but there was no significant change in the control group after treatment( P >0. 05). [Conclusions]Two treatment methods have been effective in this clinical study. We found that the expression level of MMP3 was decreased significantly after treatment in 2 therapies,which can be clinically applied.
文摘Osteoarthritis (OA) is a chronic, painful disease affecting articulating joints in man and animals. It is characterized by cartilage breakdown, bone remodeling, osteophyte formation and joint inflammation. Currently used non-steroidal anti-inflammatory drugs for the management of OA are known to have deleterious side effects. To address the need for alternatives, we evaluated the anti-inflammatory effects of a combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU) and chondroitin sulfate (CS) by measuring chemokine MCP-1 (monocyte chemoattractant protein 1, CCL2) and prostaglandin E-2 (PGE2) in stimulated chondrocytes. As the only cellular constituents of cartilage, chondrocytes are the source of pro-inflammatory mediators that play critical roles in the pathogenesis of OA. Chondrocytes were incubated: with: 1) control media, 2) [ASU + GLU + CS] combination, or 3) Phenylbutazone (PBZ) for 24 hours. Cells were next stimulated with IL-1β or LPS for another 24 hrs. MCP-1 and PGE2 from supernatants were quantitated by immunoassay. Another set of chondrocytes seeded in chamber slides were stimulated with IL-1β for 1 hour and then immunostained for NF-κB. Chondrocytes stimulated with IL-1β or LPS significantly increased MCP-1 and PGE2 production which were significantly reduced after treatment with [ASU + GLU + CS]. In contrast, PBZ significantly reduced PGE2 but not MCP-1 production. IL-1β stimulation induced nuclear translocation of NF-κB, which was inhibited by pre-treatment with either [ASU + GLU + CS] or PBZ. The present study provides evidence that the production of MCP-1 by chondrocytes can be inhibited by the combination of [ASU + GLU + CS] but not by PBZ. In contrast, PGE2 production was inhibited by either treatment suggesting that the production of MCP-1 and PGE2 could be independently regulated. The finding of distinct effects of [ASU + GLU + CS] on MCP-1 and PGE2 synthesis supports a scientific rationale for a multimodal treatment approach in the management of OA.
基金supported by CAMS Innovation Fund for Medical Sciences(2022-I2M-2-002 and 2022-I2M-1e014,China)the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-JKCS-019,China).
文摘Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage.Traditional treatments for OA are limited to alleviating various OA symptoms.There is a lack of drugs available in clinical practice that can truly repair cartilage damage.Here,we developed the chondroitin sulfate analog CS-semi5,semi-synthesized from chondroitin sulfate A.In vivo,CS-semi5 alleviated inflammation,provided analgesic effects,and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model.A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats,revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment.Binding prediction revealed that miR-122-5p acted on the 30-untranslated region of p38 mitogen-activated protein kinase,which was related to MMP13 regulation.Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis,which was further validated in the articular cartilage of OA rats.This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5,revealing its cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.
基金University Grant Commission,New Delhi for the financial support in the form of Senior Research FellowshipDr.Reddy's Laboratories Ltd.(Hyderabad, India) for providing diacerein as gift sample
文摘The present study was undertaken to investigate the effect of diacerein on the histopathology of articular cartilage and subchondral bone of the femorotibial joint in rats. Osteoartbritis was induced in rats after single intra-articular injection of sodium iodoacetate. Rats were sacrificed 1, 2, 4, and 8 weeks post intra-articular injection to evaluate the progression of histopathogenesis of osteoarthritis. Diacerein was orally administered (15 mg/kg) once daily post 1 and 2 weeks of iodoacetate injection in two groups, respectively, for up to 12 weeks. Articular cartilage and sub- chondral bone of the rats of both groups were examined after 8 and 12 weeks, respectively. Quantitative histological analyses were performed by scoring these sections as per the OARSI system. Chondroitin sulfate was also estimated in articular cartilage by decrease in absorbance of methylene blue on complexation with chondroitin sulfate using a spectrophotometer. Intra-articular injection of iodoacetate induced loss of articular cartilage with progressive sub- chondral bone sclerosis and degeneration. Based on histopathological and biochemical findings, diacerein treatment showed chondroprotective effect. Furthermore, the chondroprotective effect of diacerein was found to be more pro- nounced after 12 weeks as compared to 8 weeks in both cases (i.e., post 1 and 2 weeks of iodoacetate injection). Similar results were observed by investigation of chondroitin sulfate during biochemical study, showing the chon- droprotective effect. In conclusion, diacerein exhibits chondroprotective effect in rats with late onset of action.
基金Supported by the National Science Foundation of China (31801527)Focus on Research and Development Plan in Shandong Province (2019JZZY011003+5 种基金2018YFJH04012016CYJS07A01)Taishan Industry Leading Talent(tscy20180103)Shandong Provincial Natural Science Foundation(ZR2016CB04)Major Program of National Natural Science Foundation of Shandong Province (ZR2017ZB0208)Cultivation Project of Shandong Synthetic Biotechnology Innovation Center (sdsynbio-2018-PY-02)。
文摘Glucosamine,referred to as Glc N,is a product in which one hydroxyl group of glucose is replaced by one amino group. Glc N is widely present in plants,animals and microorganisms. After research,ammonia sugar has a good effect on the treatment of osteoarthritis,the suppression of cancer,and the recovery of cognitive impairment caused by hypoxia in some animals. This article summarized the application of Glc N in the medical field,and lays a foundation for the further development of Glc N in the field of biomedicine.
基金supported by the Key research and development program of Zhejiang Province(No.2021C03113)the Natural Science Foundation of Zhejiang Province(No.LD21E030001).
文摘Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters over-expressed reactive oxygen species(ROS),extracellular matrix disintegration,and apoptosis of chondrocytes.In this study,a kind of ROS-scavenging,biodegradable and drug-free nanoparticles(PP NPs)were constructed by the crosslinking of poly(propylene fumarate)(PPF)and ROS-scavenging poly(thioketal)(PTK).The high content of PTK and high crosslinking density of PPF and PTK innovatively endowed the NPs with slow degradation and prolonged ROS-elimination ability.The NPs were further surface-modified with chondroitin sulfate(CS),one of the dietary supplements for osteoarthritis.The intrinsic properties of resultant PP-CS NPs were excavated in vitro and in vivo.The PP-CS NPs could desirably consume 1,10-diphenyl-2-picrylhydrazyl(DPPH)radicals without toxicity to RAW264.7 cells in vitro.With an average diameter of~300 nm,the PP-CS NPs could be intra-articular administrated in OA rats and showed prolonged joint retention time,allowing only one injection per month.Moreover,the PP-CS NPs possessed a prolonged ROS depletion and M2 macrophage induction effect,down-regulated inflammatory cytokines,and reduced glycosaminoglycans loss.Consequently,the PP-CS NPs protected articular surface erosion,inhibited uneven cartilage matrix,and attenuated OA progression.