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To evaluate the traits and rheological properties of thermosensitive in situ gel of Yihuang Decoction and its common gel for vaginal use, and predict the release behavior of Yihuang Decoction in situ gel in vitro. Poloxamer was used as thermosensitive material to prepare Yihuang Decoction vaginal in situ gel, and Yihuang Decoction common gel was prepared with carbopol. Then the differences of the two gels before and after diluting with vaginal fluid were compared. The rheological parameters of Yihuang Decoction in situ gel and its common gel were determined with Anton Paar MCR102 rheometer. In addition, berberine hydrochloride was selected as an index component to evaluate the in vitro release properties of Yihuang Decoction vaginal thermosensitive in situ gel. Yihuang Decoction vaginal thermosensitive in situ gel was Newtonian fluid under low-temperature conditions, which was yellow and transparent. After reaching the gelling temperature of 24.5 ℃, it became semi-solid, pseudoplastic fluid. The gelling temperature was predicted to be 37 ℃, and the phase transition time was 30 s after diluting with simulated vaginal fluid. However, the rheological properties of Yihuang Decoction common gel had no significant changes with temperature. Compared with in situ gel, the color of common gel was darker and more translucent. Besides, its mobility was stronger after diluting with simulated vaginal fluid. The in vitro release study showed that the kinetic behavior of berberine hydrochloride in Yihuang Decoction vaginal thermosensitive in situ gel was matched with the Higuchi equation. Through simulation of vaginal administration, physical properties and dynamic rheological parameters were used to intuitively and scientifically evaluate the two gels. Compared with the common gel, the thermosensitive in situ gel could quickly attached to the vaginal mucosa and release drug, and thus was more suitable for developing vaginal administration of Yihuang Decoction, which also provides references for studying new vaginal preparation of Yihuang Decoction.
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Female , Humans , Administration, Intravaginal , Drugs, Chinese Herbal/chemistry , Gels/chemistry , Poloxamer , Rheology , Temperature , ViscosityABSTRACT
Objective: To prepare nerve growth factor(NGF) temperature sensitive in situ gel and investigate its therapeutic effect on sciatic nerve injury of rats.Method: NGF thermosensitive gel was prepared and its prescription was optimized by central composite design-response surface methodology.Fifty rats were randomly divided into the normal group,model group,NGF injection group(10 mg·L-1),NGF low-dose(10 mg·L-1) and high-dose(20 mg·L-1) thermosensitive gel groups,and sciatic nerve injury model of rats was established.The effect of NGF thermosensitive gel on the injury of sciatic nerve were comprehensively examined by taking rat behavior,sciatic nerve function index(SFI),time of withdrawal reflex,wet weight ratio of gastrocnemius muscle,and histomorphological changes as indicators.Result: The gelation temperature of NGF thermosensitive gel was 35.2℃ after the formulation being optimized,which was in line with the standard for injection.Four-eight weeks after operation,the SFI and wet weight ratio of gastrocnemius muscle in rats of NGF high-dose thermosensitive gel group were significantly higher than those in the model group and NGF injection group,but its time of withdrawal reflex was significantly lower than those in the model group and NGF injection group,and the effect was in a dose-dependent manner.Arrangement of regenerated nerve fibers in sciatic nerve injury area of rats from NGF high-dose thermosensitive gel group was more tidy,dense and continuous than that of the model group.Conclusion: NGF thermosensitive gel can promote repair of sciatic nerve injury in rats.
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OBJECTIVE: To prepare curcumin (CUR) -Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (CUR-PLGA) thermosensitive in-situ gel (CUR-PLGA-GEL), and to study pharmacokinetic characteristics of it in aqueous humor of rabbits.METHODS: CUR-PLGA was prepared with modified emulsion-solvent evaporation method. CUR-PLGA-GEL was prepared by cold-dissolving method using poloxamer407 (P407) and poloxamer 188 (P188) as gel matrix. The level of CUR in gel was determined by HPLC, and the irritation of it to rabbit eyes was investigated (self-control of left and right eyes of 5 rabbits were taken, while the Draize test was used to evalvate the irritation). 10 New Zealand white rabbits were randomly divided into 2 groups, with 5 rabbits in each group. Left eyes were given CUR-PLGA-GEL and CUR suspension (containing CUR 8 mg), respectively. The concentrations of CUR in aqueous humor of rabbits were determined before medication and 1, 2, 4, 6, 8, 10, 12, 24 h after medication. The pharmacokinetic parameters were calculated by using DAS 2. 0 software. RESULTS: CUR-PLGA-GEL was successfully prepared and the total score of irritation was 0, which indicated irritative to rabbits. In aqueous humor of rabbits, cmax and AUC0-24 h of CUR-PLGA-GEL were 2. 48 and 2. 71 fold of CUR suspension. CONCLUSIONS: Prepared CUR-PLGA-GEL can be used for ophthalmic delivery and can improve the utilization of CUR in the eye.
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Objective: Optimize to obtain the in situ gel of matrine with thermosensitivity and rectal retention of bioadhesion rectum. Methods: Thermosensitive gel was prepared by cold method, and then using gelation temperature as an indicator, central combination design-response surface method (CCD-RSM) was used to optimize the dosage of P407, P188, and CMC-Na. Texture Analyzer was used to measure the gel strength and adhesion of prescription, the rectal retention was investigated by rectal administration, and the release rate was explored by modified paddle method. Results: The optimal prescription was matrine 2%, CMC-Na 1.0%, P188 1.3%, P407 16.5%, and benzalkonium bromide 0.02%. The prescription gel did not leak after rectal administration in rats, which can remain in the body for more than 6 h, in vitro release in line with Weibull model. Conclusion: The optimized matrine-loaded thermosensitive in situ gel could meet the requirement of rectal administration.
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Objective: To optimize the formula and preparation process of metronidazole thermosensitive in situ gel.Methods: The temperature of gelation and 24-h cumulative release were used as the evaluation indices, and the orthogonal tests were carried out to investigate the amounts of poloxamer 407 (P407), poloxamer 188 (P188), sodium alginate and polyethylene glycol 4000 (PEG 4000) to screen the best formula of thermosensitive in situ gel.The in vitro release of metronidazole thermosensitive in situ gel was determined by HPLC and compared with that of commercially available gel.Results: The optimum formula of thermosensitive in situ gel was P407 of 20%, P188 of 18%, sodium alginate of 0.1% and PEG 4000 of 1.5%.The release rate of metronidazole thermosensitive in situ gel was high, and the temperature of gelation was suitable.Compared with that of the commercially available gel, the vaginal retention of the in situ gel was significantly improved.Conclusion: The formula of the in situ gel is reasonable and the preparation process is feasible.
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Objective:To prepare norfloxacin thermosensitive in situ gel and investigate its in vitro drug release behavior. Meth-ods:Poloxamer 407 and poloxamer 188 were used as the matrix of norfloxacin thermosensitive in situ gel,and the gel was prepared by a cold dissolving method. The formula was optimized by a central composite design-response surface method. In vitro drug release be-havior of norfloxacin thermosensitive in situ gel was studied as well. Results:Within a certain concentration range, the gelation tem-perature decreased gradually with the amount increase of poloxamer 407, and that increased gradually with the amount increase of poloxamer 188. The optimal formula was as follows:the concentration of poloxamer 407 was 20.6%(w/v),and that of poloxamer 188 was 5.7%(w/v),which obtained suitable gelling temperature. The release of norfloxacin from the thermosensitive in situ gel reached up to (87.5% ± 5.4% 7 in 6 h. Conclusion: Norfloxacin thermosensitive in situ gel has excellent temperature sensitivity, and can slow down the drug release,which shows potential use for vaginal drug delivery system.
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Objective: To observe the rheological properties of octoxynol-9 vaginal thermosensitive in situ gel [(O-9)-VTG] for predicting the gelation behavior in vivo, and evaluate the retention ability in vagina.Methods: The rheological parameters of (O-9)-VTG and (O-9)-VTG diluted by stimulant vaginal fluid (SVF) were measured by a Haake Rheomix to characterize the rheological properties.The vaginal samples after the administration of self-made (O-9)-VTG and O-9 gel were withdrawn, and then the concentration of octoxynol-9 in the samples was determined to evaluate the retention ability.Results: (O-9)-VTG was Newtonian fluid with low viscoelasticity under room temperature and converted to gel at 32.6℃.The formula could still transform into gel at body temperature after diluted by SVF, and resided in the vagina of mice above 8 h.Conclusion: (O-9)-VTG has suitable gelation temperature and rheological properties.Compared with the self-made octoxynol-9 gel, (O-9)-VTG has satisfactory retention in vagina, which meets the requirements for vaginal topical use.
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OBJECTIVE:To optimize Azelastine hydrochloride (AH) thermosensitive in-situ gel nasal drops formulation. METHODS:Using poloxamer 407(P407)and poloxamer 188(P188)as excipients,AH thermosensitive in-situ gel was prepared by cold solution method. The formulation was optimized by central composite design-response surface methodology using the amount of P407 and P188(g/100 ml)as factors and phase-transition temperature as index. Binomial expression was fitted,and pre-dicted and measured values were compared. RESULTS:The correlation coefficient R2 fitted by binomial expression was equal to 0.986 5. The optimal formulation was as follows as P407 for 20.414 4%,P188 for 5.035 4%,measured value of(30.81±0.02)℃, predicted values of 31 ℃,deviation of 0.61%. CONCLUSIONS:AH thermosensitive in-situ gel nasal drops formulation is opti-mized by central composite design-response surface methodology.
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The study was designed to generate an ophthalmic thermosensitive in situ gel with improved mechanical and mucoadhesive properties that may prolong the retention time to enhance the bioavalability of pearl hydrolyzate. The gene was comprised of poloxamer 407, poloxamer188 and Carbopol 934, which were optimized by central composite design and response surface methodology. The rheological properties, transcorneal permeability, retention time and in vitro release behaviors of the optimal gel formulation were investigated. The gel was Newtonian liquid at 25℃ and performed as a semisolid gel with non-Newtonian liquid property with a gelation time of 13 s at 35℃. Compared with a conventional eye drops, the ophthalmic in situ gel exhibited a sevenfold increase in retention with a sustained release behavior, which was observed with suitable permeability coefficient at 5.58 cm·s-1. In conclusion, the new gel of pearl hydrolyzate prolonged the release duration of drug, which may decrease the frequency of administration of pearl hydrolyzate. kilometers with ecological similarity between 20% and 40%, mainly in Yunnan, Guangxi, Guangdong, Guizhou, Hainan, Sichuan, Fujian and Chongqing. The climate factors mainly affecting the distribution of Panax notoginseng (Burk.) F. H. Chen were precipitation of warmest quarter, SD of temperature seasonality, altitude, isothermality, coefficient of variation of precipitation seasonality, mean temperature of monthly, precipitation of driest month, reference bulk density of soil and soil texture.
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Gabexate mesilate (GM) is a trypsin inhibitor, and mainly used for treatment of various acute pancreatitis, including traumatic pancreatitis (TP), edematous pancreatitis, and acute necrotizing pancreatitis. However, due to the characteristics of pharmacokinetics, the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration, which is difficult to manage. Specially, when the blood supply of pancreas is directly damaged, intravenous administration is difficult to exert the optimum therapy effect. To address it, a novel thermosensitive in-situ gel of gabexate mesilate (GMTI) was developed, and the optimum formulation of GMTI containing 20.6% (w/w) P-407 and 5.79% (w/w) P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro, and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin (HE) staining, and its curative effect on grade II pancreas injury was also evaluated by testing amylase (AMS), C-reactive protein (CRP) and trypsinogen activation peptide (TAP), and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/mL in GM group and GMTI group, respectively (P<0.05 vs. P-407), and completely inhibited at 10.0 and 20.0 mg/mL (P<0.01 vs. P-407). After local injection of 10 mg/mL GMTI to rat leg muscular tissue, muscle fiber texture was normal, and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore, the expression of AMS, CRP and TAP was significantly increased in TP group as compared with control group (P<0.01), and significantly decreased in GM group as compared with TP group (P<0.01), and also slightly inhibited after 1.0 and 5.0 mg/mL GMTI treatment as compared with TP group (P<0.05), and significantly inhibited after 10.0 and 20.0 mg/mL GMTI treatment as compared with TP group (P<0.01). HE staining results demonstrated that pancreas cells were uniformly distributed in control group, and they were loosely arranged, partially dissolved, with deeply stained nuclei in TP group. Expectedly, after gradient GMTI treatment, pancreas cells were gradually restored to tight distribution, with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes, and alleviate the severity of trauma-induced pancreatitis, and had a potential drug developing and clinic application value.
Subject(s)
Animals , Male , Rats , Amylases , Metabolism , C-Reactive Protein , Metabolism , Delayed-Action Preparations , Pharmacokinetics , Pharmacology , Gabexate , Chemistry , Pharmacokinetics , Pharmacology , Gels , Muscle, Skeletal , Oligopeptides , Metabolism , Pancreas , Pathology , Pancreatitis , Drug Therapy , Pathology , Poloxamer , Chemistry , Rats, Sprague-Dawley , Serine Proteinase Inhibitors , Chemistry , Pharmacokinetics , Pharmacology , Temperature , Wounds, Penetrating , Drug Therapy , PathologyABSTRACT
Objective To investigate the release feature of dexamethasone sodium phosphate from thermosensitive in situ gels in vitro. Methods Rotation rheometer was used to measure the changes of viscosity with temperature. The membraneless model was applied in assessing corrosion behavior of gel using a thermostatic shaker (50 r/min) at an amplitude of 2.5 cm, taking phosphate buffered solution (pH 7.2) as releasing media. The release behavior was investigated by HPLC on a C18 reverse column DiamonsilTM (250 mm?4.6 mm, 5 ?m). The mobile phase consisted of triethylamine solution-methanol-acetonitrile (38∶28∶34), pumped at 1.0 ml/min, and the detection wavelength was set at 242 nm. Results When the temperature was near to the sol-gel transition temperature, the viscosity rose suddenly. Taking dexamethasone sodium phosphate (2 ml, pH 7.2) as media, the gel dissolution and drug release rate followed the zero order kinetics, and the cumulative gel dissolution (Q1) and cumulative drug release (Q2) equations were Q1=0.8238t (r=0.999, P