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
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
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
A selective precolumn derivatization liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of glucosamine in human plasma and urine has been developed and validated. Glucosamine was d...A selective precolumn derivatization liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of glucosamine in human plasma and urine has been developed and validated. Glucosamine was derivatized by o-phthalaldehyde/3-mercaptopropionic acid. Chromatographic separation was performed on a Phenomenex ODS column (150 mm 4.6 mm, 5 mm) using linear gradient elution by a mobile phase consisting of methanol (A), and an aqueous solution containing 0.2% ammonium acetate and 0.1% formic acid (B) at a flow rate of 1 mL/min. Tolterodine tartrate was used as the internal standard (IS). With protein precipitation by acetonitrile and then the simple one-step derivatization, a sensitive bio-assay was achieved with the lower limit of quantitation (LLOQ) as low as 12 ng/mL for plasma. The standard addition calibration curves suitable for clinical sample analysis showed good linearity over the range of 0.012-8.27 mg/mL in plasma and 1.80-84.1 mg/mL in urine. The fully validated method has been successfully applied to a pharmacokinetic study of compound glucosamine sulfate dispersible tablets in health Chinese volunteers receiving single oral doses at 500, 1000 and 1500 mg of glucosamine sulfate, as well as multiple oral doses of 500 mg t.i.d. for 7 consecutive days.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(GS) and chondroitin sulfate(CS) are common over-the-counter(OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicit...Glucosamine(GS) and chondroitin sulfate(CS) are common over-the-counter(OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicity with these supplements. We reported a unique case of drug-induced cholestasis caused by GS and CS in a combination tablet. The etiology of the jaundice was overlooked despite extensive investigations over a three-month period. Unlike drug-induced hepatocellular injury, drug-induced cholestatic jaundice with GS and CS has only been reported twice before. This case emphasizes the importance of a complete medication history, especially OTC supplements, in the assessment of cholestasis.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
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
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
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
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 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
The present study is performed to investigate the effect of two different glucosamine containing drugs: Drug 1 and Drug 2 (D1 and D2) against CCl4 induced brain damage in male albino rats. Liverin (AM) was employed in...The present study is performed to investigate the effect of two different glucosamine containing drugs: Drug 1 and Drug 2 (D1 and D2) against CCl4 induced brain damage in male albino rats. Liverin (AM) was employed in the current study as an antioxidant reference drug. CCl4 administration caused a significant elevation in the levels of MDA and NO of brain tissue, in association with a significant decrease in the antioxidant defense system (GSH, SOD and GPX) that indicated the induction of oxidative stress in brain tissue. CCl4 administration induced brain injury as manifested by the obtained changes in neurotransmitter parameter (norepinephrine (NE), Dopamine (DA), Serotonin (5-HT), and Acetylcholinesterase AChE). The tested nutraceuticals and the antioxidant drug displayed a significant improvement against the undue effect of CCl4 via decreasing the brain tissue content of MDA, NO with the elevation of GSH content. Also, the significant increase in SOD and GPX enzymatic activity was obtained when compared to CCL4 group. In addition AM, D1, and D2 have an ameliorative effect on neurotransmitter parameter NE, DA, 5HT, and AChE. Results of this study suggest that both antioxidant drugs and tested nutraceuticals palliate the brain injuries through anti-oxidative effect, with the elimination of the deleterious effect of toxic metabolites of CCl4 on brain tissue.展开更多
A new functional glycomonomer was obtained from modified glucosamine. Hemoglobin-imprinted polymer gel was prepared with allyl-bromide modified glucosamine as functional monomer, poly(ethylene-glycol)diacrylate (PEGDA...A new functional glycomonomer was obtained from modified glucosamine. Hemoglobin-imprinted polymer gel was prepared with allyl-bromide modified glucosamine as functional monomer, poly(ethylene-glycol)diacrylate (PEGDA) as cross-linker and ammonium persulfate [(NH4)2S2O8]/sodium hydrogen sulfite (NaHSO3) as initiators in a phosphate buffer. The adsorption capacity and selective adsorption of the molecular imprinting polymer (MIP) were also discussed.展开更多
Background: During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized...Background: During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized that supplementing gestating dams with glucosamine during this time would support placental folded-epithelial-bilayer development and increase litter size. In Exp. 1, gilts were unilaterally hysterectomizedovariectomized(UHO). UHO gilts were mated and then supplemented daily with 10 g glucosamine(n = 16) or glucose(control, n = 17) from d 85 of gestation until slaughter(d 105). At slaughter, the number of live fetuses was recorded and each live fetus and its placenta was weighed. Uterine wall samples adjacent to the largest and smallest fetuses within each litter were processed for histology. In Exp. 2, pregnant sows in a commercial sow farm were supplemented with either 10 g glucosamine or glucose daily from d 85 of gestation to farrowing. Total piglets born and born alive were recorded for each litter. In Exp. 3, the same commercial farm and same protocol were used except that the dose of glucosamine and glucose was doubled to 20 g/d.Results: In Exp. 1, the number of live fetuses tended to be greater in glucosamine-treated UHO gilts(P = 0.098).Placental morphometry indicated that the width of the folded bilayer was greater(P = 0.05) in glucosamine-treated gilts. In Exp. 2, litter size did not differ between glucosamine-and glucose-treated sows. However in Exp. 3, the increased dose of glucosamine resulted in a significant treatment by parity interaction(P ≤ 0.01), in which total piglets born and born alive were greater in glucosamine treated sows of later parity(5 and 6).Conclusions: These results indicated that glucosamine supplementation increased the width of the folds of the placental bilayer and increased litter size in later parity, intact pregnant commercial sows.展开更多
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A selective precolumn derivatization liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of glucosamine in human plasma and urine has been developed and validated. Glucosamine was derivatized by o-phthalaldehyde/3-mercaptopropionic acid. Chromatographic separation was performed on a Phenomenex ODS column (150 mm 4.6 mm, 5 mm) using linear gradient elution by a mobile phase consisting of methanol (A), and an aqueous solution containing 0.2% ammonium acetate and 0.1% formic acid (B) at a flow rate of 1 mL/min. Tolterodine tartrate was used as the internal standard (IS). With protein precipitation by acetonitrile and then the simple one-step derivatization, a sensitive bio-assay was achieved with the lower limit of quantitation (LLOQ) as low as 12 ng/mL for plasma. The standard addition calibration curves suitable for clinical sample analysis showed good linearity over the range of 0.012-8.27 mg/mL in plasma and 1.80-84.1 mg/mL in urine. The fully validated method has been successfully applied to a pharmacokinetic study of compound glucosamine sulfate dispersible tablets in health Chinese volunteers receiving single oral doses at 500, 1000 and 1500 mg of glucosamine sulfate, as well as multiple oral doses of 500 mg t.i.d. for 7 consecutive days.
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.
文摘Glucosamine(GS) and chondroitin sulfate(CS) are common over-the-counter(OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicity with these supplements. We reported a unique case of drug-induced cholestasis caused by GS and CS in a combination tablet. The etiology of the jaundice was overlooked despite extensive investigations over a three-month period. Unlike drug-induced hepatocellular injury, drug-induced cholestatic jaundice with GS and CS has only been reported twice before. This case emphasizes the importance of a complete medication history, especially OTC supplements, in the assessment of cholestasis.
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.
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.
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.
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.
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.
文摘The present study is performed to investigate the effect of two different glucosamine containing drugs: Drug 1 and Drug 2 (D1 and D2) against CCl4 induced brain damage in male albino rats. Liverin (AM) was employed in the current study as an antioxidant reference drug. CCl4 administration caused a significant elevation in the levels of MDA and NO of brain tissue, in association with a significant decrease in the antioxidant defense system (GSH, SOD and GPX) that indicated the induction of oxidative stress in brain tissue. CCl4 administration induced brain injury as manifested by the obtained changes in neurotransmitter parameter (norepinephrine (NE), Dopamine (DA), Serotonin (5-HT), and Acetylcholinesterase AChE). The tested nutraceuticals and the antioxidant drug displayed a significant improvement against the undue effect of CCl4 via decreasing the brain tissue content of MDA, NO with the elevation of GSH content. Also, the significant increase in SOD and GPX enzymatic activity was obtained when compared to CCL4 group. In addition AM, D1, and D2 have an ameliorative effect on neurotransmitter parameter NE, DA, 5HT, and AChE. Results of this study suggest that both antioxidant drugs and tested nutraceuticals palliate the brain injuries through anti-oxidative effect, with the elimination of the deleterious effect of toxic metabolites of CCl4 on brain tissue.
基金the National Natural Science Foundation of China(No.50673044)for financial support.
文摘A new functional glycomonomer was obtained from modified glucosamine. Hemoglobin-imprinted polymer gel was prepared with allyl-bromide modified glucosamine as functional monomer, poly(ethylene-glycol)diacrylate (PEGDA) as cross-linker and ammonium persulfate [(NH4)2S2O8]/sodium hydrogen sulfite (NaHSO3) as initiators in a phosphate buffer. The adsorption capacity and selective adsorption of the molecular imprinting polymer (MIP) were also discussed.
基金partially supported by the Nebraska Pork Producers Council[grant number 14–238]
文摘Background: During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized that supplementing gestating dams with glucosamine during this time would support placental folded-epithelial-bilayer development and increase litter size. In Exp. 1, gilts were unilaterally hysterectomizedovariectomized(UHO). UHO gilts were mated and then supplemented daily with 10 g glucosamine(n = 16) or glucose(control, n = 17) from d 85 of gestation until slaughter(d 105). At slaughter, the number of live fetuses was recorded and each live fetus and its placenta was weighed. Uterine wall samples adjacent to the largest and smallest fetuses within each litter were processed for histology. In Exp. 2, pregnant sows in a commercial sow farm were supplemented with either 10 g glucosamine or glucose daily from d 85 of gestation to farrowing. Total piglets born and born alive were recorded for each litter. In Exp. 3, the same commercial farm and same protocol were used except that the dose of glucosamine and glucose was doubled to 20 g/d.Results: In Exp. 1, the number of live fetuses tended to be greater in glucosamine-treated UHO gilts(P = 0.098).Placental morphometry indicated that the width of the folded bilayer was greater(P = 0.05) in glucosamine-treated gilts. In Exp. 2, litter size did not differ between glucosamine-and glucose-treated sows. However in Exp. 3, the increased dose of glucosamine resulted in a significant treatment by parity interaction(P ≤ 0.01), in which total piglets born and born alive were greater in glucosamine treated sows of later parity(5 and 6).Conclusions: These results indicated that glucosamine supplementation increased the width of the folds of the placental bilayer and increased litter size in later parity, intact pregnant commercial sows.
