Impact of inflammatory bowel disease on Japanese patients' quality of life: results of a patient questionnaire survey.

BACKGROUND: Inflammatory bowel disease (IBD) has a significant negative impact on quality of life (QOL); however, the direct impact of IBD on several aspects of patients' lives is unknown. The IMPACT survey was conducted in Europe in 2010-2011 to determine this impact. We conducted the IMPACT survey in Japan and compared the results between subgroups of patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The 52-item IMPACT survey questionnaire assessing treatment and the impact of IBD on patients' lives was translated into Japanese and administered to IBD patients recruited through patient advocacy groups. RESULTS: Between June 2013 and January 2014, 172 Japanese IBD patients completed the questionnaire (including 84 UC and 83 CD patients). Half of all patients (84/172, 48.8 %) were satisfied with their treatment plan, and half of those who had undergone surgery were satisfied with the outcome (46/87, 52.9 %). Although 34.9 % (60/172) of patients had not been hospitalized in 5 years, 50.0 % (86/172) had been hospitalized for more than 10 days. During the most recent flare, 49.4 % (85/172) of patients had to reschedule appointments because of IBD. Moreover, 32.0 % (55/172) of patients had to make adjustments such as working part-time or at home to avoid taking sick days; 35.5 % (61/172) of patients felt that they had lost a job because of IBD. CONCLUSIONS: Our survey results indicate that IBD patients' lives and social activities are affected by the deterioration of QOL due to IBD and its symptoms.

Sustained-release self-dissolving micropiles for percutaneous absorption of insulin in mice.

Microparticles-adsorbed insulin and zinc insulin (PenfilN) were molded to self-dissolving micropiles (SDMPs) with chondroitin sulfate as the base for the percutaneous administration of insulin. Porous silicon dioxide (Sylysia 320, 440 and 730) and porous calcium silicate (FloriteRE) were used as microparticles. As a reference, insulin loaded SDMPs were prepared. SDMPs were percutaneously administered to mice at the insulin dose level of 2.5 IU/kg. After the insertion of SDMPs to mouse skin, blood samples were collected for 8 h and plasma glucose levels were measured. There were not significant differences on minimum plasma glucose levels between the test preparations. However, T(mins), the time when the minimum glucose level appeared were 1.5 +/- 0.2 h (Sylysia 320), 1.3 +/- 0.2 h (Sylysia 440), 1.6 +/- 0.4 h (Sylysia 730), 2.1 +/- 0.3 h (Florite) and 1.7 +/- 0.3 h (zinc insulin) which were greater than insulin SDMP, 0.8 +/- 0.1 h. In addition, greater hypoglycemic effects were observed with SDMPs containing adsorbent-insulin and/or zinc insulin than insulin SDMP. The mean AACs (area above the plasma glucose level vs. time curve) of SDMPs containing adsorbent-insulin and zinc insulin were 357.8% h for FloriteRE, 333.1% h for Sylysia 320, 308.1% h for Sylysia 440, 328.1% h for Sylysia 730, and 374.7% h for zinc insulin, respectively, which were about two folds higher than that of insulin SDMN, 161.2% h. Those results suggest the usefulness of SDMPs composed of adsorbent-insulin as a long-acting percutaneous insulin preparation.

Feasibility of microneedles for percutaneous absorption of insulin.

Insulin loaded microneedles were prepared using dextrin as the base for the percutaneous administration of insulin. Under room temperature, insulin solution was added to high concentration of dextrin solution, glue, and microneedles were prepared by forming thread with polypropylene tips. The mean weight of the microneedles was 0.59+/-0.01 (S.E.) mg. The mean length and basal diameter were 3.24+/-0.16 and 0.55+/-0.03 mm, respectively. Five microneedles were percutaneously administered to mice at the insulin dose levels of 0.5, 1.0 and 2.5IU/kg. After administration, blood samples were collected for 5 h and plasma glucose levels were measured. Lowest plasma glucose level appeared at 1 h after the administration of microneedles and dose-dependent hypoglycemic effect of insulin was clearly observed in those dose range. By comparing the mean area above the plasma glucose level versus time curve (AAC) between microneedle preparation and i.v. solution, the pharmacological availabilities were calculated to be 97.7% (0.5IU/kg), 93.3% (1.0IU/kg) and 91.3% (2.5IU/kg), respectively. When highly loaded insulin loaded microneedle was administered to mice with one microneedle, there was not a significant difference on the plasma glucose level versus time curves between 5 and 1 microneedle experiments. In vitro release study showed that almost all of the formulated insulin was released within 1 h. The T50% was estimated to be 15.4+/-1.1 min. Stability of insulin in the microneedle preparations showed that the remaining insulin after 1 month of the storage were 98.2% (-80 degrees C), 98.9% (20 degrees C) and 99.0% (40 degrees C). Evans blue (EB) loaded microneedles were also prepared and histological study was performed with HWY-Slc hairless rats. The diffusion of EB from the microneedle to the environmental skin reached to the maximum at 3 h after administration. The scab was formed at 24 h after administration. The wound formed by the administration of microneedle was cured at 72 h after administration. Those results suggest the usefulness of a self-dissolving microneedle for the percutaneous delivery of peptide/protein drugs like insulin.