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Study on Intranasal Brain-Targeting System of Trybizine Hydrochloride

Author: ZhouXiaoTong
Tutor: TaoTao
School: Shanghai Institute of Pharmaceutical Industry
Course: Pharmacy
Keywords: Hydrochloric cone dual net Blood-brain barrier HP-β-CD Poloxamer 407 PEG6000 Intranasal administration Orthogonal test
CLC: S859
Type: Master's thesis
Year: 2006
Downloads: 143
Quote: 0
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Abstract


Hydrochloric cone double net (trybizine hydrochloride, SIPI-1029, T-46) is a new anti- trypanosome drug discovered and developed by the Shanghai Institute of Pharmaceutical Industry efficiency and low toxicity , as veterinary medicine has completed clinical trials , reporting production . Pharmacodynamics indicate that it does not cure the central nervous system (central nervous system, CNS) infections in mice , and this may be because the hydrophilicity of the drug , it is difficult through the blood-brain barrier ( the blood- brain barrier, BBB ) . People trypanosome infection , trypanosomes invade the CNS. The purpose of this project is to promote drug through the BBB , through the preparation of studies and make it effective insecticidal concentration in the CNS . Determination of the apparent solubility under different pH conditions of T-46 and the apparent oil / water partition coefficient, worth the increased with pH of the solution , T - 46 the equilibrium solubility increases gradually and reaches the maximum at about 6 , and then increases with pH gradually decreases; worth the increased with the pH of the solution , T - 46 oil-water distribution coefficient is gradually increased , and reaches the maximum at about 6 . The cisterna magna intubation collecting cerebrospinal fluid , blood samples were collected with a tail blood . HPLC method for the determination of the T -46 in the cerebrospinal fluid and blood , its sensitivity can achieve the requirements of the pharmacokinetic studies . In order to investigate the phase transition temperature , through bovine olfactory mucosa the cumulative diffusion amount and in vitro cumulative release amount test indicators , by orthogonal experiment situ gelling agent, poloxamer 407 concentration , the phase transition temperature moderator PEG6000 concentration and promote transparent agent HP-β-CD concentration of three factors , derived T-46 in situ gel is preferably prescription consisting of : 1.5 % T -46 , 20 % poloxamer 407,2.5% PEG6000, 2.5% HP-β -CD, 0.9% benzyl alcohol. Formulation stability , and good reproducibility . Intranasal administration in rats in situ gel and intravenous injection of T-46 T-46 solution the nasal administration plasma AUC of PLASMA < / sub> for 26.8% of the intravenous injection of cerebrospinal fluid T-46 AUC CSF is 2.68 times the intravenous and display significant brain targeting T - 46 in situ gel nasal administration . Studies have shown that , with good prospects for the development of the T - 46 in situ gel as a nasal brain targeted drug delivery system .

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CLC: > Agricultural Sciences > Livestock, animal medicine,hunting,silkworm,bee > Animal Medicine ( Veterinary Medicine) > Veterinary Pharmacology
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