The initial reports of liver injury attributed to Move Free were published in 2010, with subsequent reports in 2012 and 2013, all from the United States. These publications described an acute hepatocellular injury arising within 1 to 3 weeks of starting a Move Free product that contained glucosamine, chondroitin and a proprietary herbal mixture of Chinese skullcap (Scutellaria baicalensis) and black catechu (Acacia catechu). The injury was moderate in severity and resolved within 1 to 2 months of stopping the supplement. Immunoallergic and autoimmune features were not present, and the injury resolved without residual in all cases. One patient restarted the product after at least partial recovery and redeveloped a similar pattern of liver injury. While further cases have not been described, prospective studies of drug induced liver injury from the United States mentioned 3 cases of acute liver injury linked to Move Free products, all from 2012-2013. At present, Move Free products do not list a proprietary herbal component but do mention a proprietary mineral complex with a similar name: “Uniflex”.
Chitosan may form complexes with chondroitin sulfate decreasing its absorption. Therefore, chondroitin sulfate should not be used concomitantly with chitosan. /Chondroitin sulfate/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于昏迷、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿...。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常...。开始静脉输注5%葡萄糖水（D5W）/SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%盐水（NS）或乳酸林格液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象...。使用地西泮或劳拉西泮治疗癫痫...。使用丙美卡因氢氯化物协助眼部冲洗...。/Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
/ALTERNATIVE and IN VITRO TESTS/ To test the effectiveness of glucosamine (GluNH(2))-HCl, chondroitin sulfate (CS) and mixtures in protecting cartilage exposed to fibronectin fragments (Fn-fs), an exposure known to enhance catabolic cytokines and matrix metalloproteinases (MMPs). Pharmacologic formulations of GluNH(2) (FCHG49) and CS (TRH122) (Nutramax Laboratories, Inc.) were added at 1, 10 or 100 microg/ml singly or in mixtures to bovine cartilage cultures in serum or serum-free conditions with or without Fn-f. Proteoglycan (PG) release into media and remaining cartilage PG content were measured by dye binding analysis and effects on PG synthesis by assays of 35-sulfate incorporation. Effects on MMP-3 and -13 expression were measured by Western blotting of conditioned media. In serum-free conditions, the agents singly or as mixtures did not block Fn-f mediated matrix degradation. In serum, single agents were weakly effective at 100 ug/ml, while the mixture of each agent at 0.1 ug/ml decreased PG loss by about 50% by day 7 and at 1 ug/ml restored nearly 50% of the PG after 7 days in Fn-f pretreated cartilage. However, both agents singly and as mixtures at 0.1-100 microg/ml decreased MMP release. In serum, the single agents at 1-10 ug/ml weakly reversed Fn-f mediated PG synthesis suppression, while the mixtures were 100% effective at 1 ug/ml. GluNH(2) and CS act synergistically in reversing damage and promoting repair at concentrations found in plasma after oral ingestion of these agents. Reversal of PG synthesis suppression correlates more with these activities than suppression of MMP-3 or -13 expression.
Plasma chondroitin sulfate (CS) amount and charge density were determined in 45 healthy volunteers (control group), 45 pseudoxanthoma elasticum (PXE)-affected patients and 19 healthy carriers by using fluorophore-assisted carbohydrate electrophoresis (FACE) and HPLC equipped with postcolumn derivatization and fluorescence detection. The mean values of chondroitin sulfate amount were 4.9 + or -1.21 for volunteers, 4.7 + or -1.40 for pseudoxanthoma elasticum subjects and 4.4 + or - 1.44 for the carriers. No significant differences were found for the three human subjects groups. On the contrary, by considering the age of normal volunteers, a significant increase of plasma chondroitin sulfate amount was measured. In fact, the volunteers aging from 17 to 40 years (mean 32.1) showed a chondroitin sulfate concentration of 4.3 + or - 1.30 while the group ranging from 50 to 74 years (mean 56.9) had a value of 5.6 + or - 1.16 with a significant increase of +30.2%. The same significant increase in chondroitin sulfate plasma content with increasing age was measured for pseudoxanthoma elasticum-affected and healthy carriers group. Extracted plasma chondroitin sulfate was evaluated for the main two unsaturated disaccharides, non-sulfated and 4-monosulfated, and the charge density determined. The mean values were 0.54 + or - 0.13 for volunteers, 0.60 + or -0.15 for PXE subjects and 0.50 + or - 0.15 for the carriers. A significant increase of +11.1% was found between the pseudoxanthoma elasticum patients and healthy human group but no differences were calculated between the control group and the carriers. Furthermore, besides a chondroitin sulfate amount, the volunteers aging from 17 to 40 years (mean 32.1) showed a charge density of 0.53 + or - 0.14 while the group ranging from 50 to 74 years (mean 56.9) had a value of 0.58 + or - 0.17 with a significant increase of +9.4%. The same trend was measured for the healthy carriers group. The chondroitin sulfate charge density of pseudoxanthoma elasticum-affected subjects was found to increase significantly more than healthy controls depending on the age. In fact, the pseudoxanthoma elasticum patients aging from 10 to 40 years (mean 29.3) showed a charge density of 0.56 + or - 0.14 while the group ranging from 50 to 74 years (mean 58.6) had a value of 0.67+/-0.11 with a significant increase of +19.6%. Furthermore, the group of pseudoxanthoma elasticum-affected subjects ranging from 50 to 74 years (mean 58.6) showed a significant increase of 15.5% in comparison with the group matched for age (mean 56.9) of healthy volunteers.
Chondroitin sulfate was labelled by reduction with sodium 3(H)-borohydride and administered by oral route in the rat and dog. More than 70% of radioactivity was absorbed and found in urine and tissues. The plasma radioactivity was fractionated by size-exclusion chromatography in three fractions: radioactivity associated with high, intermediate and low molecular mass compounds. The peak value of the concentration of high molecular mass radioactivity compounds in plasma was reached after 1.6 and 2.1 hr for the rat and dog, respectively. After 36 hr the high molecular mass radioactivity compounds were still present in plasma of dog and rat. After 24 hr radioactivity was higher in the intestine, liver, kidneys, synovial fluid and cartilage than in other tissues. ...
Earlier studies using high-molecular-weight chondroitin sulfate, concluded that there was no significant absorption of this high-molecular-weight version of chondroitin sulfate. More recent studies demonstrate that there is probably significant absorption of low-molecular-weight chondroitin sulfate. Absorption appears to occur from the stomach and small intestine. There is also an indication that some chondroitin sulfate, after absorption, does enter the joint space. ... /Chondroitin sulfate/
The purpose of this study was to determine if glucosamine (GL) hydrochloride (FCHG49) and low molecular weight (LMW) chondroitin sulfate (CS) (TRH122) are absorbed after oral administration to horses. The bioavailability of LMWCS was evaluated by quantifying the total disaccharides found in the plasma following chondroitinase ABC digestion. Two separate studies were conducted. In study 1, ten adult horses received the following four treatments in a randomized crossover fashion: (1) i.v. LMWCS (3 g of 8 kDa), (2) p.o. LMWCS (3 g of 8 kDa), (3) i.v. LMWCS (3 g of 16.9 kDa) and (4) p.o. LMWCS (3 g of 16.9 kDa). Each group received 9 g GL with LMWCS. In a second study, each horse (n=2) was randomly assigned to receive either i.v. administration of GL HCl (9 g) or p.o. administration of GL HCl (125 mg/kg). Blood samples were collected, assayed and pharmacokinetic parameters were determined. GL was absorbed after oral dosing with a mean C(max) of 10.6 (6.9) ug/ml and a mean T(max) of 2.0 (0.7) hr. The extent of absorption of LMWCS after dosing with both the 8.0 and 16.9 kDa provides evidence that LMWCS is absorbed orally. C(max) and AUC were higher (p<0.05) for the 16.9 kDa material compared with 8.0 kDa. However, the 16.9 kDa bioavailability was less than 8.0 kDa, but this difference was not significant. This study provides the first report of the bioavailability of orally administered GL and LMWCS in the horse.
