| Allergic rhinitis (allergic rhinitis, AR) is the Department of Otolaryngology common disease, one of the most dangerous, great harm, some patients are often associated with asthma or bronchial hyperresponsiveness symptoms, if not properly treated even develop pulmonary heart disease, severe Affecting the patient's physical and mental health and quality of life. Domestic and international data show that, AR population prevalence rate of about 25%, and with the country to improve the degree of industrialization has increased. Andrographolide (AND) is the active ingredient of Andrographis paniculata, which has anti-inflammatory, antibacterial and antiviral effects. It is widely used in diseases such as rhinitis, pharyngitis and upper respiratory tract infection. It is known as natural broad-spectrum antibiotic medicine. Natural anti-penetrating agent, with anti-inflammatory, anti-allergic effects and improve microcirculation, clinical mainly for the treatment of AR, acute and chronic rhinitis and other rhinitis, To Xinyi oil as penetration enhancer, played a dual role in promoting osmotic treatment. However, due to the poor solubility of AND, and conventional nasal preparations easy to loss, poor compliance, short stay and other shortcomings, it is difficult to achieve the purpose of effective prevention and treatment. Therefore, in this experiment, liposomal (LIP) and temperature-sensitive coagulation (TSG) gel were combined to prepare andrographolide liposomal temperature-sensitive gel (AND-LIP-TSG) composite preparation, which combined their advantages and complement each other is not enough to extend Drug retention time, delay drug release, thereby increasing the bioavailability of AND in nasal administration, with a view to AND-LIP-TSG treatment of AR diseases provide a theoretical basis. The contents of this paper are as follows:1. In this study, the HPLC method was established for the determination of the content of AND. The solubility of AND and the determination of the partition coefficient of AND and oil were studied before prescription. The result showed that 1gP was 0.42, which indicated that AND and water were poorly soluble. Therefore, the preparation of AND into liposomes, the hope that the use of its lipophilic hydrophilic properties to promote AND mucosal transmission.2. The optimal formulation of AND-LIP was screened with the OD value as the drug loading and encapsulation efficiency. The star-point design was used to prepare the AND-LIP for ethanol injection, reverse evaporation and thin film dispersion. The optimal preparation process was optimized by thin-film dispersion method, and the optimum preparation process was optimized.3. The entrapment efficiency of AND-LIP was (69.87 ± 1.78)%, with a regular zeta potential of (-42.5 ± 2.7) mV and a uniform size distribution of (97.8 ± 7.2) nm. The encapsulation efflciency, particle size, potential, pH and POV of the AND liposomes prepared under these conditions were all stable. The results showed that the stability of the preparation was good. The optimal formulation of temperature-sensitive gel matrix was optimized by the same method, and AND-LIP-TSG was prepared. The effect of different concentrations of penetration enhancers on the permeability of nasal mucosa was investigated. The results showed that 5% magnolia oil had the best effect on the penetration of the nasal mucosa. In addition, It was found that AND-LIP-TSG containing 5% transdermal enhancers had higher permeation and retention of nasal mucosa than other preparations. The in vitro release characteristics of different preparations of AND were examined by dialysis bag method. The results showed that AND-LIP-TSG could effectively delay drug release.4. The quality, stability, irritation and nasal absorption of AND-LIP-TSG were investigated. The results showed that AND-LIP-TSG had good stability and no obvious irritation to the nasal mucosa. The mean nasal retention time (MRT) of the nasal cavity was 7.75 min and the mean nasal cavity retention time 1.11 times the normal temperature sensitive gel.As of September 2016, the database was searched and no reports of the combination of AND-LIP and TSG for nasal administration to treat AR have been found. In this study, AND liposome and temperature-sensitive gel combined to form a binary preparation, the preparation of AND-LIP-TSG at room temperature for the fluid, nasal physiological conditions immediately under the phase transition into semi-solid gel state, not only improve the AND The nasal retention time, delay drug release, and easy to administer, the patient compliance is good, at the same time, its stability is good, and no irritation of the nasal mucosa, safe and reliable for nasal administration of AR and other diseases provide theoretical basis, Is expected to become an effective treatment of AR new formulations. |
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