Cyclosporine formulations for use in treatment of bronchiolitis obliterans syndrome (BOS)
一种细支气管炎、环孢素的技术，应用在包含环孢素A的药物组合物领域，能够解决未提及治疗效果、未提及研究结果等问题
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Embodiment 1
[0227] Example 1: In Vitro Nebulization Characterization of Liquid CsA Formulations
[0228] Preparation of active substance CsA (Ph.Eur.) and excipients lipoid S100, polysorbate 80, disodium edetate, disodium hydrogen phosphate dodecahydrate and sodium dihydrogen phosphate monohydrate Cyclosporin liposomal liquid formulation for inhalation. The formulations were adjusted to physiologically tolerated values for pH (6.5±0.2) and osmolality (350-450 mOsmol / kg).
[0229] using a mixing chamber The nebulizer produces an aerosol and the volume of the mixing chamber is about 95ml. The aerosols produced by this nebulizer were characterized using breath simulation, laser diffraction and impactor measurements. The results of these measurements are summarized in Table 1.
[0230] Table 1: with Aerosol characteristics of liposomal cyclosporine (L-CsA) formulations nebulized by nebulizer
[0231] Nominal drug amount [mg] 15.0±0.4 MMD [μm] 2.8±0.1 DD[%] 75....
Embodiment 2
[0235] Example 2: In vitro aerosol characterization of reconstituted CsA formulations
[0236] Sucrose was added to the formulation described in Example 1 as a lyoprotectant. Afterwards, the formulation was lyophilized. Immediately before nebulization, the formulation was reconstituted with 2.3 ml of 0.25% saline. After reconstitution, the size of the liposomes is in the range of 40-100 nm (0.040-0.10 μm), and the polydispersity index is less than 0.40.
[0237] With the same inhalation chamber as the nebulizer in Example 1 (i.e. a mixing chamber with a volume of about 95 ml) The nebulizer nebulizes the reconstituted formulation. The results of the aerosol profile data generated by the reconstituted formulation are shown in Table 2.
[0238] Compared with Example 1, the results are not substantially different.
[0239] Table 2: with Aerosol properties of reconstituted cyclosporine liposomal formulations nebulized by a nebulizer
[0240] Fill volume [ml] 2.5...
Embodiment 3
[0242] Example 3: Clinical trials of inhaled cyclosporine for BOS
[0243] Research Inclusion:
[0244] Forty-three patients were assessed for eligibility, of whom 23 met the eligibility criteria. Before randomization, one patient died and one patient withdrew. Twenty-one patients were randomized; 11 in the L-CsA treatment group and 10 in the SOC treatment group. ( figure 1 ) One patient in the L-CsA treatment group withdrew from the study due to progressive skin cancer during the 24-week follow-up period. In this case, standard systemic immunosuppressive therapy was discontinued.
[0245] Patients with BOS 1 or BOS 2 were eligible if they had no untreated infection and no airway narrowing on bronchoalveolar lavage (BAL) bronchoscopy before randomization and at week 24 and when clinically indicated. qualifications.
[0246] The bronchiolitis obliterans syndrome (BOS) grading was applied as follows: based on bimonthly FEV 1 Measurement, continuous BOS assessment. The de...
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