An alkylpolyglucoside surfactant as a prospective pharmaceutical excipient for topical formulations: The influence of oil polarity on the colloidal structure and hydrocortisone in vitro/in vivo permeation

There is a growing need for research into new skin- and environment-friendly surfactants. This paper focuses on a natural surfactant of an alkylpolyglucoside type, which can form both thermotropic and lyotropic liquid-crystalline phases. The aim of this study was to relate some physicochemical properties (characterised by polarisation and transmission electron microscopy, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, to the results of in vitro and in vivo bioavailability of hydrocortisone (HC). The three formulations contained oils of different polarity (medium chain triglycerides: MG, isopropyl myristate: IPM and light liquid paraffin: LP), respectively. In vitro permeation was followed through the artificial skin constructs (ASC), while the parameters measured in vivo were erythema index: EI (using instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration (SCH). The vehicles based on cetearyl glucoside and cetearyl alcohol showed a complex colloidal structure of lamellar liquid-crystalline and lamellar gel-crystalline type, depending on oil polarity. Rheological profile of the vehicle was directly related to the in vitro profile of the HC permeation. In vivo results suggested that the vehicle with MG retarded the HC permeation, whereas less polar IPM and non-polar LP enhanced it. It is suggested that the enhancement is achieved either by a direct interaction with lipid lamellae of the SC or indirectly by improving skin hydration.

There were no adverse effects during in vivo study, which indicates a good safety profile of this alkylpolyglucoside surfactant.     

氢化可的松注射液在光作用下的稳定性研究

目的　用灯光为光源研究药物在自然光照射下的稳定性。方法　采用自制的光量累积仪 ,用脉冲计数法对自然光进行累积计量 ,研究氢化可的松注射液在灯光及自然光照射下的含量变化规律 ;探讨不同光源对该药物稳定性的影响 ;并预测该药物在室内自然光照射下的贮存期。结果　氢化可的松注射液在光照试验中的含量变化遵从零级动力学规律 :C=C0 - k Et;在无外包装条件下 ,室内自然光照射下的贮存期约为 36天 ,与留样测得的结果 35天基本一致。结论　采用灯光照射实验可研究药物在自然光照射下的稳定性。     

Anti-inflammatory activity of hamamelis distillate applied topically to the skin

Summary The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle.UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry.The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity.     

The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers

Rationale: Corticosteroids are elevated in certain neuropsychiatric disorders and this may contribute to the neuropsychological impairments reported in these disorders. Objective: To examine the effects of hydrocortisone on learning, memory and executive function. Methods: Hydrocortisone 20 mg was administered twice daily for 10 days to normal male volunteers in a randomized, placebo control, crossover, within-subject design. Learning, memory and executive function were measured using selected subtests from the Cambridge Neuropsychological Test Automated Battery. Results: Hydrocortisone caused impairments of visuo-spatial memory. These included increased within search errors and impaired use of strategies on the spatial working memory subtest. In addition, administration of hydrocortisone was associated with more errors in the paired associate learning subtest, although no effect was found on the Tower of London. Hydrocortisone speeded response latencies in certain tests (pattern and spatial recognition memory). Conclusion: These results indicate that chronic administration of hydrocortisone leads to deficits in certain tests of cognitive function sensitive to frontal lobe dysfunction and may contribute to the cognitive impairment reported in certain neuropsychiatric disorders. Received: 27 July 1998 / Final version: 9 February 1999     

10例带状疱疹性角膜炎、虹膜睫状体炎的治疗体会

目的 评价静滴氢化可的松、0．5％阿托品眼液与0．5％托吡酰胺眼液点眼在治疗带状疱疹性角膜炎、虹膜睫状体炎中的疗效。方法 在带状疱疹性角膜凝、虹膜睫状体炎的早期应用静滴氢化可的松、0．5％阿托品眼液与0．5％托吡酰忮眼液点眼。结果 虹膜睫状体炎症缓解，角膜炎症被控制。结论 在带状疱疹性角膜炎、虹膜睫状体炎早期应用静滴氢化可的松。0．5％阿托品眼液与0．5％托吡酰忮眼液点眼疗效确切，可降低虹膜睫状体炎的并发症。     

旋光法用于氢化可的松生产过程的控制

通过对氢化可的松发酵过程中用比色法控制发酵过程和终点改为旋光法控制,使测定过程的控制更加合理有效。     

In Vitro and In Vivo Evaluations of Dihydroquinoline- and Dihydroisoquinoline-based Targetor Moieties for Brain-specific Chemical Delivery Systems

Brain-targeted delivery of various drugs can be successfully achieved by chemical delivery systems (CDS) that contain a 1,4-dihydropyridine-based redox targetor moiety and undergo a sequential metabolism. However, the susceptibility of this moiety toward hydration in acidic media may limit the shelf-life of such compounds in aqueous formulation. Here, a systematic investigation of the chemical stability toward oxidation and hydration of ester and amide derivatives of 3-substituted 1,4-dihydropyridine, 1,4-dihydroquinoline, and 4-substituted 1,2-dihydroisoquinoline is reported, together with the in vitro stability and in vivo (rat) distribution of isoquinoline-based testosterone and hydrocortisone chemical delivery systems, which were selected as having the most suitable acid-resistant targetor moieties.     

低剂量琥珀酸氢化可的松对感染性休克患者血清细胞因子的影响

目的:探讨低剂量琥珀酸氢化可的松对感染性休克患者血清细胞因子的影响.方法:将80例感染性休克患者随机分为对照组和治疗组两组,各40例,均采取常规对症治疗,另外治疗组加用琥珀酸氢化可的松,比较两组血清肿瘤坏死因子(TNF-α)、白细胞介素-1(IL-1)和白细胞介素-6(IL-6)的水平差异及两组临床治疗效果.结果:两组治疗前TNF-α、IL-1和IL-6水平比较,差异无统计学意义(P＞0.05);而治疗组治疗后1、2、3、7d时TNF-α水平均明显低于对照组,差异具有统计学意义(P＜0.05);治疗组治疗后2、3、7d时IL-1、IL-6水平均明显低于对照组,差异具有统计学意义(P＜0.05);治疗组病死率、MODS发生率均明显低于对照组,差异具有统计学意义(P＜0.05);治疗组机械通气时间、ICU住院时间均较对照组明显减少,差异具有统计学意义(P＜0.05).结论:低剂量琥珀酸氢化可的松对感染性休克患者血清细胞因子TNF-α、IL-1和IL-6均具有明显的抑制作用,且能减轻患者组织器官损伤,降低患者病死率,具有较好的临床应用和推广价值.