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101.
HR Costantino JD Andya PA Nguyen N Dasovich TD Sweeney SJ Shire CC Hsu YF Maa 《Canadian Metallurgical Quarterly》1998,87(11):1406-1411
We have examined the stability and aerosol performance of the pharmaceutical protein recombinant humanized anti-IgE monoclonal antibody (rhuMAbE25) spray dried with mannitol. The aerosol performance was measured by the fine particle fraction (FPF), and stability was assessed by the formation of soluble aggregates. When mannitol was added to the spray-dried rhuMAbE25 formulation, its ability to stabilize the protein leveled off above about 20% (w/w, dry basis). The FPF of the spray-dried formulations was stable during storage for rhuMAbE25 containing 10% and 20% mannitol, but the 30% formulation exhibited a dramatic decrease upon storage at both 5 degreesC and 30 degreesC, due to mannitol crystallization. We tested the addition of sodium phosphate to a 60:40 rhuMAbE25:mannitol (w:w) mixture, which otherwise crystallized upon spray drying and yielded a nonrespirable powder. The presence of sodium phosphate was successful in inhibiting mannitol crystallization upon spray drying and dramatically lowering the rate of solid-state aggregation. However, over long-term storage some crystallization was observed even for the phosphate-containing samples, concomitantly with increased particle size and decreased suitability for aerosol delivery. Therefore, the physical state of mannitol (i.e., amorphous or crystalline) plays a role both in maintaining protein stability and providing suitable aerosol performance when used as an excipient for spray-dried powders. Agents which retard mannitol crystallization, e.g., sodium phosphate, may be useful in extending the utility of mannitol as an excipient in spray-dried protein formulations. 相似文献
102.
103.
Three new dammarane-type triterpenoid saponins, bacopasaponins A, B and C, of biological interest have been isolated from the reputed Indian medicinal plant Bacopa monniera and identified as 3-O-alpha-L-arabinopyranosyl-20-O-alpha-L-arabinopyranosyl-+ ++jujubogenin, 3-O-[alpha-L-arabinofuranosyl (1--> 2)alpha-L-arabinopyranosyl]pseudojujubogenin and 3-O-[beta-D-glucopyranosyl (1 -->3)[alpha-L-arabinofuranosyl (1--> 2)]alpha-L-arabinopyranosyl]pseudojujubogenin by spectroscopic methods and some chemical transformations. The hitherto undetermined configurations at C-20 and C-22 of pseudojujubogenin were elucidated by phase-sensitive ROESY, and 1H and 13C signals of the saponins were assigned by DEPT, 1H-1H COSY, HSQC and HMBC techniques. 相似文献
104.
HE Greenberg MJ England ET Hellriegel TD Bjornsson 《Canadian Metallurgical Quarterly》1997,37(6):480-485
The time of peak concentration after administration of oral drug is an often quoted and used pharmacokinetic parameter. It is not well appreciated, however, that the peak times after a single dose and a dose at steady state during a multiple administration regimen can differ significantly. This article derives the mathematical relationships that determine how a peak time at steady state differs from that after a single or first dose. These relationships are then evaluated using three different approaches: 1) graphic simulations of time courses of drug concentration for three hypothetical drugs; 2) comparisons of predicted and observed peak times using examples from the literature; and 3) comparisons of predicted and simulated peak times based on different sampling schedules for three hypothetical drugs. The key finding is that peak times after a dose at steady state can occur considerably earlier after administration than after a single dose. However, the manner by which peak times are usually determined, that is, the sampling time corresponding to the highest measured drug concentration, imposes significant limitations on the usefulness of this parameter. 相似文献
105.
Chordomas are uncommon tumors arising from embryonic remnats of the fetal notochord. The spheno-occipital and sacrococcygeal regions account for over 90 per cent of cases, the remaining 10 per cent occurring anywhere along the vertebral axis. A case of chordoma arising from the clivus is presented with a view to discussing management. The ability to obtain reasonable survival times associated with a useful and meaningful quality of life is emphasized. This may be accomplished by repeated, judicious surgical intervention with surprising ease and little morbidity to the patient in spite of its intracranial location. 相似文献
106.
To determine whether excretion of high concentrations of long chain fatty acids might be associated with high colon cancer risk, we compared concentrations of major long chain fatty acids in the feces of four populations at different risk for colon cancer. Concentrations of C18:1 were found to be significantly higher (P less than 0.05) in the feces of the two high risk populations than in the feces of the two low risk populations. 相似文献
107.
TD Swinscow 《Canadian Metallurgical Quarterly》1976,2(6036):632-634
108.
Nine cases of sacro-iliac pyarthrosis are presented. The difficulty in localizing the infection is attributable mostly to failure to appreciate the posteriorly situated physical findings. This, and the difficulty with early roentgenographic demonstration of the lesion, may lead to unnecessary abdominal exploration (as in two of our patients) or to prolonged delay in diagnosis and hence spread of the infection. Awareness of the usual physical findings and prompt use of radioisotope scanning to localize the infection led to earlier diagnosis and avoidance of surgery in three patients seen recently. Antibiotic therapy, with or without surgery, led to cure in all patients, with minimum sequelae. 相似文献
109.
M Aratow SM Fortney DE Watenpaugh AG Crenshaw AR Hargens 《Canadian Metallurgical Quarterly》1993,74(6):2763-2770
The effect of lower body negative pressure (LBNP) on transcapillary fluid balance is unknown. Therefore, our objective was to assess leg interstitial fluid pressures (IFP), leg circumference, plasma volume (PV), and net whole body transcapillary fluid transport (TFT) during and after supine LBNP and to evaluate the addition of oral saline ingestion on transcapillary exchange. Six healthy men 23-41 yr old underwent 4 h of 30 mmHg LBNP, followed by 50 min of supine recovery on two separate occasions, once with and once without ingestion of 1 liter of isotonic saline. IFP was measured continuously in subcutis as well as superficial and deep regions of the tibialis anterior muscle by slit catheters. TFT was calculated by subtracting urine production and calculated insensible fluid loss from changes in PV. During exposure to LBNP, IFP decreased in parallel with chamber pressure, foot venous pressure did not change, leg circumference increased by 3 +/- 0.35% (SE) (P < 0.05), and PV decreased by 14 +/- 2.3%. IFP returned to near control levels after LBNP. At the end of minute 50 of recovery, PV remained decreased (by 7.5 +/- 5.2%) and leg circumference remained elevated (by 1 +/- 0.37%). LBNP alone produced significant movement of fluid into the lower body but no net TFT (-7 +/- 12 ml/h). During LBNP with saline ingestion, 72 +/- 4% of the ingested fluid volume filtered out of the vascular space (TFT = 145 +/- 10 ml/h), and PV decreased by 6 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
110.
TD Swinscow 《Canadian Metallurgical Quarterly》1976,2(6037):680-681