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1.
Chrzanowski F 《AAPS PharmSciTech》2008,9(2):646-650
Two numerical methods, Decision Analysis (DA) and Potential Problem Analysis (PPA) are presented as alternative selection
methods to the logical method presented in Part I. In DA properties are weighted and outcomes are scored. The weighted scores
for each candidate are totaled and final selection is based on the totals. Higher scores indicate better candidates. In PPA
potential problems are assigned a seriousness factor and test outcomes are used to define the probability of occurrence. The
seriousness-probability products are totaled and forms with minimal scores are preferred. DA and PPA have never been compared
to the logical-elimination method. Additional data were available for two forms of McN-5707 to provide complete preformulation
data for five candidate forms. Weight and seriousness factors (independent variables) were obtained from a survey of experienced
formulators. Scores and probabilities (dependent variables) were provided independently by Preformulation. The rankings of
the five candidate forms, best to worst, were similar for all three methods. These results validate the applicability of DA
and PPA for candidate form selection. DA and PPA are particularly applicable in cases where there are many candidate forms
and where each form has some degree of unfavorable properties.
Presented at the 41st Annual Pharmaceutical Technologies Arden Conference—Oral Controlled Release Development and Technology,
January 2006, West Point NY. 相似文献
2.
Chrzanowski F 《AAPS PharmSciTech》2008,9(2):639-645
Practical examples of preformulation support of the form selected for formulation development are provided using several drug
substances (DSs). The examples include determination of the solubilities vs. pH particularly for the range pH 1 to 8 because of its relationship to gastrointestinal (GI) conditions and dissolution
method development. The advantages of equilibrium solubility and trial solubility methods are described. The equilibrium method
is related to detecting polymorphism and the trial solubility method, to simplifying difficult solubility problems. An example
of two polymorphs existing in mixtures of DS is presented in which one of the forms is very unstable. Accelerating stability
studies are used in conjunction with HPLC and quantitative X-ray powder diffraction (QXRD) to demonstrate the differences
in chemical and polymorphic stabilities. The results from two model excipient compatibility methods are compared to determine
which has better predictive accuracy for room temperature stability. A DSC (calorimetric) method and an isothermal stress
with quantitative analysis (ISQA) method that simulates wet granulation conditions were compared using a 2 year room temperature
sample set as reference. An example of a pH stability profile for understanding stability and extrapolating stability to other
environments is provided. The pH-stability of omeprazole and lansoprazole, which are extremely unstable in acidic and even
mildly acidic conditions, are related to the formulation of delayed release dosage forms and the resolution of the problem
associated with free carboxyl groups from the enteric coating polymers reacting with the DSs. Dissolution method requirements
for CR dosage forms are discussed. The applicability of a modified disintegration time (DT) apparatus for supporting CR dosage
form development of a pH sensitive DS at a specific pH such as duodenal pH 5.6 is related. This method is applicable for DSs
such as peptides, proteins, enzymes and natural products where physical observation can be used in place of a difficult to
perform analytical method, saving resources and providing rapid preformulation support.
Presented at the 41st Annual Pharmaceutical Technologies Arden Conference—Oral Controlled Release Development and Technology,
January 2006, West Point NY. 相似文献
3.
Solids dispersions (SDs) have been proposed as an alternative to improve the dissolution rate of low solubility drugs. SDs
containing albendazole (ABZ; 5, 10, 25, and 50% w/w) and Pluronic 188 (P 188) as hydrophilic carrier were formulated. The obtained SDs were assessed in comparison to physical
mixtures (PMs). Drug–polymer interactions in solid state were investigated using Fourier-transform infrared spectroscopy,
scanning electron microscopy, and X-ray diffraction analysis. No chemical interaction was found between ABZ and poloxamer.
The dissolution profiles indicated that ABZ incorporated in SDs and PMs was rapidly released, reaching rapidly the steady
state. Increased dissolution rates are usually observed at the highest polymer proportions. However, an opposite effect for
SDs as well as for PMs was observed in the assays described here. The systems with the lowest P 188 percentages (SD4, SD3;
PM4, PM3) tended to be more effective in increasing the ABZ dissolution rate. Such a result can be attributed to the fact
that concentrated aqueous solutions of Poloxamer may form thermo-reversible gels. The physical–mechanical properties indicated
that SDs possess improved flow and compacting properties compared to PMs. Thus, ABZ SDs would be more convenient for solid
dosage form design and manufacture. 相似文献
4.
Airaksinen S Karjalainen M Kivikero N Westermarck S Shevchenko A Rantanen J Yliruusi J 《AAPS PharmSciTech》2005,6(2):E311-E322
Phase transformations in formulations can lead to instability in physicochemical, biopharmaceutical, and processing properties
of products. The influences of formulation design on the optimal dosage forms should be specified. The aim here was to investigate
whether excipients with different water sorption behavior affect hydrate formation of nitrofurantoin in wet masses. Nitrofurantoin
anhydrate was used as a hydrate-forming model drug, and 4 excipients with different water-absorbing potential (amorphous low-substituted
hydroxypropylcellulose, modified maize starch, partially amorphous silicified microcrystalline cellulose, and crystalline
α-lactose monohydrate) were granulated with varying amounts of purified water. Off-line evaluation of wet masses containing
nitrofurantoin anhydrate and excipient (1∶1) was performed using an X-ray powder diffractometer (XRPD) and near-infrared spectroscopy,
and drying phase was evaluated by variable temperature XRPD. Only amorphous excipient in the formulation retarded hydrate
formation of an active pharmaceutical ingredient (API) at high water contents. Hygroscopic partially crystalline excipient
hindered hydrate formation of API at low water contents. Crystalline excipient was unable to control hydrate formation of
API. The character of excipient affects the stability of formulation. Thus, correct selection of excipients for the formulation
can control processing-induced phase transitions and improve the storage stability of the final dosage form.
Published: October 6, 2005 相似文献
5.
Aafke M. Schipper Kim Lotterman Marten Geertsma Rob S. E. W. Leuven A. Jan Hendriks 《Biodiversity and Conservation》2010,19(7):2087-2110
Four arthropod datasets of different taxonomic detail were compared on their discriminatory power for various environmental
characteristics in a lowland floodplain area along the river Rhine. The arthropod datasets comprised ground-dwelling arthropods
at class-order level (n = 10), beetle families (n = 32), ground beetle genera (n = 30) and ground beetle species (n = 68). Environmental characteristics included vegetation characteristics, hydro-topographic setting, physical–chemical soil
properties and soil contamination levels. Relations between arthropod assemblages and environmental factors were assessed
with variance partitioning: a multivariate statistical approach that attributes variation in community composition to specific
explaining variables. The variance partitioning showed comparable results for the four datasets. A substantial part of the
variation (31–38%) could be ascribed to vegetation characteristics. Variance could further be attributed to physical–chemical
soil properties (7–10%), hydro-topographic setting (3–7%) and soil metal contamination (2–4%). Thus, in strongly heterogeneous
landscapes like lowland river floodplains, relatively coarse taxonomic data can already provide a valuable indication of the
relative importance of different environmental factors for structuring arthropod communities. However, the ground beetles
showed a higher specificity for different vegetation types and a more distinct relation to soil contamination levels than
the other arthropod datasets. Hence, a higher degree of taxonomic detail will be beneficial for investigating the consequences
of for example environmental pollution or vegetation characteristics in terms of taxonomic diversity or community composition. 相似文献
6.
Ravichandran Mahalingam Bhaskara Jasti Raj Birudaraj Dimitrios Stefanidis Robert Killion Tom Alfredson Pratap Anne Xiaoling Li 《AAPS PharmSciTech》2009,10(1):98-103
Compacts containing selected bioadhesive polymers, fillers, and binders were investigated for their potential as a bioadhesive
gastroretentive delivery system to deliver water soluble and water insoluble compounds in the stomach. Compacts with 90:10,
75:25, and 60:40 of polyvinylpyrrolidone (PVP) and polyethylene oxide (PEO) were evaluated for swelling, dissolution, bioadhesion,
and in vitro gastric retention. Compacts containing higher PEO showed higher swelling (111.13%) and bioadhesion (0.62 ± 0.03 N/cm2), and retained their integrity and adherence onto gastric mucosa for about 9 h under in vitro conditions. In vivo gastroretentive property of compacts were evaluated in Yorkshire cross swines. Compacts containing 58% PVP, 40% PEO and 2%
of water soluble or water insoluble marker compounds showed gastroadhesive and retentive properties in vivo. It is concluded that PEO in combination with PVP yields a non disintegrating type bioadhesive dosage form which is suitable
for gastroretentive applications.
A part of this study has been presented at the Controlled Release Society’s symposium held at Vienna, 2006. 相似文献
7.
Using computer simulation, we evaluated the impact of using first-generation information to increase selection efficiency
in a second-generation breeding program. Selection efficiency was compared in terms of increase in rank correlation between
estimated and true breeding values (i.e., ranking accuracy), reduction in coefficient of variation of correlation coefficients
(i.e., ranking reliability), and increase in realized gain, with best linear unbiased prediction (BLUP). The test populations
were generated with varying parameters: selection strategy (forward vs backward selection of parents); number of parents (24∼96);
number of crosses per parent (1∼8); heritability (0.05∼0.35); ratio of dominance to additive variance (0∼3); ratio of additive-by-site
to additive variance (0∼3); and ratio of dominance-by-site to additive variance (0∼3). The two selection strategies gave distinct
results. When parents of the second-generation crosses had been selected via backward selection, adding first-generation information
markedly increased selection efficiency. Conversely, when parents had been selected via forward selection, first-generation
information provided little increase in efficiency. The amount of increase depended more on heritabilities in both generations
and less on dominance and genotype–by–environment effects. Including first-generation information helped more when there were
many parents and few crosses per parent in the second generation. Only in the case of extremely low first-generation heritabilities
was there no benefit to adding first-generation information in terms of improved ranking reliability and accuracy. 相似文献
8.
The purpose of this research was to design oral controlled release (CR) matrix tablets of zidovudine (AZT) using hydroxypropyl
methylcellulose (HPMC), ethyl cellulose (EC) and carbopol-971P (CP) and to study the effect of various formulation factors
on in vitro drug release. Release studies were carried out using USP type 1 apparatus in 900 ml of dissolution media. Release kinetics
were analyzed using zero-order, Higuchi’s square root and Ritger–Peppas’ empirical equations. Release rate decreased with
increase in polymer proportion and compression force. The release rate was lesser in formulations prepared using CP (20%)
as compared to HPMC (20%) as compared to EC (20%). No significant difference was observed in the effect of pH of dissolution
media on drug release from formulations prepared using HPMC or EC, but significant difference was observed in CP based formulations.
Decrease in agitation speed from 100 to 50 rpm decreased release rate from HPMC and CP formulations but no significant difference
was observed in EC formulations. Mechanism of release was found to be dependent predominantly on diffusion of drug through
the matrix than polymer relaxation incase of HPMC and EC formulations, while polymer relaxation had a dominating influence
on drug release than diffusion incase of CP formulations. Designed CR tablets with pH independent drug release characteristics
and an initial release of 17–25% in first hour and extending the release up to 16–20 h, can overcome the disadvantages associated
with conventional tablets of AZT. 相似文献
9.
R Prasanna M Joshi A Rana YS Shivay L Nain 《World journal of microbiology & biotechnology》2012,28(3):1223-1235
The performance of three selected bacterial strains—PR3, PR7 and PR10 (Providencia sp., Brevundimonas sp., Ochrobacterium sp.) and three cyanobacterial strains CR1, CR2 and CR3 (Anabaena sp., Calothrix sp., Anabaena sp.), and their combinations was evaluated in a pot experiment with rice variety Pusa-1460, comprising 51 treatments along
with recommended fertilizer controls. Highest yield enhancement of 19.02% was recorded in T12 (CR2), over control, while significant
enhancement in nitrogen fixing potential was recorded in treatments involving combination of bacterial-cyanobacterial strains—T37
(PR3 + CR1 + CR3) and T21 (PR7 + CR1). Organic carbon was significantly increased in all microbe-inoculated treatments, which
could be correlated with microbial biomass carbon values and activities of all the enzymes tested in our study. Also, panicle
weight and plant biomass were highly correlated with soil microbial carbon. Comparative evaluation revealed the superior performance
of strains CR2, CR1 (both Anabaena sp.) and PR10 (Ochrobacterium sp.) in increasing the growth and grain yield of rice and improving soil health, besides N (nitrogen) savings of 40–80 kg ha−1. The study for the first time illustrated the positive effects of co-inoculation of bacterial and cyanobacterial strains
for integrated nutrient management of rice crop. 相似文献
10.
Hypromellose (hydroxypropyl methylcellulose, HPMC) matrices are widely used in the formulation of sustained release dosage
forms. The integrity and performance of an HPMC matrix formulation depends on rapid hydration and gel formation upon ingestion.
Due to the recent alert issued by the Food and Drug Administration regarding the potential negative influence of alcoholic
beverages on extended release (ER) formulations, several researchers have evaluated the potential influence of hydroalcoholic
media on drug release from ER dosage forms. It has been reported that HPMC matrix formulations do not show “dose dumping”
in hydroalcoholic media. The purpose of this study was a fundamental investigation on the effect of hydroalcoholic solutions
(0–40% v/v ethanol) on textural and rheological properties of different viscosity grades of neat HPMC, as the functional ingredient
within a hydrophilic matrix. In general, hydroalcoholic solutions had little effect on gel formation and mechanical properties
of hydrated compacts, while the rheological behavior of HPMC showed dependency on the ethanol content of such solutions. 相似文献
11.
Sergey Dobretsov Raeid M. M. Abed Sultan M. S. Al Maskari Jamal N. Al Sabahi Reginald Victor 《Journal of applied phycology》2011,23(6):983-993
Polar (water) and non-polar (ethyl acetate) extracts from the cyanobacterial layer (top 1–3 mm) of four hot spring microbial
mats in the Sultanate of Oman were tested for their antibacterial, antidiatom and quorum-sensing inhibitory activities under
natural conditions. The chemical composition of the active extracts was analysed using gas chromatography–mass spectrometry
(GC-MS). Cyanobacteria within these mats were identified by direct microscopy while the total bacterial community composition
was compared using automated ribosomal intergenic spacer analysis (ARISA). Only the extracts from Bowshar and Nakhl mats showed
antibacterial properties against Bacillus sp., Micrococcus luteus, Shigella sonnei, Salmonella enterica and Klebsiella pneumoniae. All tested extracts inhibited the growth of the benthic diatom Amphora coffeaeformis. Extracts from Bowshar, Rustaq and Nakhl inhibited quorum-sensing of the reporter strains Chromobacterium violaceum CV017 and Agrobacterium tumefaciens NTL4. The highest bioactivity was recorded for ethyl acetate extracts from Nakhl mats, which had the lowest number of operational
taxonomic units (OTUs). Using GC-MS, 74 chemical compounds were obtained, however with different distribution among the four
mat extracts (similarity < 43%). Various cyanobacteria, belonging mainly to Chroococcus, Phormidium, Leptolyngbya, Spirulina and Lyngbya were detected in the different mats, and each mat had its unique bacterial community, as confirmed by ARISA profiles. We
conclude that antimicrobial and quorum-sensing inhibitory compounds can be produced by hot spring mat microorganisms under
natural conditions and the differences in these compounds could be attributed to the differences in the mats’ bacterial composition
as well as the physical–chemical conditions of the springs. 相似文献
12.
Enrico G. Funhoff Thyra E. de Jongh Bruce A. Averill 《Journal of biological inorganic chemistry》2005,10(5):550-563
To date, most spectroscopic studies on mammalian purple acid phosphatases (PAPs) have been performed at a single pH, typically pH 5. The catalytic activity of these enzymes is, however, pH dependent, with optimal pH values of 5.5–6.2 (depending on the form). For example, the pH optimum of PAPs isolated as single polypeptides is around pH 5.5, which is substantially lower that of proteolytically cleaved PAPs (ca. pH 6.2). In addition, the catalytic activity of single polypeptide PAPs at their optimal pH values is four to fivefold lower than that of the proteolytically cleaved enzymes. In order to elucidate the chemical basis for the pH dependence of these enzymes, the spectroscopic properties of both the single polypeptide and proteolytically cleaved forms of recombinant human PAP (recHPAP) and their complexes with inhibitory anions have been examined over the pH range 4 to 8. The EPR spectra of both forms of recHPAP are pH dependent and show the presence of three species: an inactive low pH form (pH<pK
a,1), an active form (pK
a,1<pH<pK
a,2), and an inactive high pH form (pH>pK
a,2). The pK
a,1 values observed by EPR for the single polypeptide and proteolytically cleaved forms are similar to those previously observed in kinetics studies. The spectroscopic properties of the enzyme–phosphate complex (which should mimic the enzyme–substrate complex), the enzyme–fluoride complex, and the enzyme–fluoride–phosphate complex (which should mimic the ternary enzyme–substrate–hydroxide complex) were also examined. EPR spectra show that phosphate binds to the diiron center of the proteolytically cleaved form of the enzyme, but not to that of the single polypeptide form. EPR spectra also show that fluoride binds only to the low pH form of the enzymes, in which it presumably replaces a coordinated water molecule. The binding of fluoride and phosphate to form a ternary complex appears to be cooperative.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
13.
Microbial selection strategies that enhance the likelihood of developing commercial biological control products 总被引:1,自引:0,他引:1
Research interest in utilizing microorganisms to create a microbial environment suppressive to plant pathogens has increased
exponentially in recent years. Despite intense interest in developing biological control agents, relatively few antagonists
have achieved ‘commercial product’ status. The fact that such a small proportion of active laboratory antagonists are developed
into biological control products is partly due to several features common to microbial selection strategies that are widely
utilized to obtain putative biological control agents: (a) relatively few candidate microorganisms are tested; (b) microbes
are selected based on the results of an assay that does not replicate field conditions; and (c) the amenability of microbes
to commercial development is excluded as a selection criterion. Selection strategies that enhance the likelihood of developing
commercial biological control products are described. These include making appropriate choices regarding the pathosystem
for biological control, the method of microbe isolation, and the method of isolate characterization and performance evaluation.
A model system of developing a biological control product active against Gibberella pulicaris (Fries) Sacc. (anamorph: Fusarium sambucinum Fuckel), the primary causal agent of Fusarium dry rot of stored potatoes, is used to illustrate the proposed selection
strategy concepts. The crucial importance and methodology is described, of selecting strains with enhanced potential for
commercial development based on a strain exhibiting both favorable growth kinetics and bioefficacy when grown in commercially
feasible liquid media.
Received 06 February 1997/ Accepted in revised form 29 May 1997 相似文献
14.
D. S. Robertson 《Neurochemical research》2010,35(5):681-687
The formation of cell membranes through the physical–chemical interaction of two hydrophilic colloidal fluids is applied to
the formation of the membranes of brain and neural cells. Also described is the membrane mechanism of transfer of ions and
compounds necessary for brain and neural cell functions into the cerebrospinal fluid through the blood–brain barrier. Changes
in the cerebrospinal fluid giving rise to degradation of brain and neural cells and the formation of precipitates within the
brain are considered. Monitoring of electrolyte changes in metabolic fluids is shown to be a possible method of predicting
the onset of degenerate brain conditions. 相似文献
15.
We compared the efficacy of artificial and natural selection processes in purging the genetic load of perpetually small populations.
We subjected replicate lines of the housefly (Musca domestica L.), recently derived from the wild, to artificial selection for increased mating propensity (i.e., the proportion of male–female
pairs initiating copulation within 30 min) in efforts to cull out the inbreeding depression effects of long-term small population
size (as determined by a selection protocol for increased assortative mating). We also maintained parallel non-selection lines
for assessing the spontaneous purge of genetic load due to inbreeding alone. We thus evaluated the fitness of artificially
and ‘naturally’ purging populations held at census sizes of 40 individuals over the course of 18 generations. We found that
the artificially selected lines had significant increases in mating propensity (up to 46% higher from the beginning of the
protocol) followed by reversed selection responses back to the initial levels, resulting in non-significant heritabilities.
Nevertheless, the ‘naturally’ selected lines had significantly lower fitness overall (a 28% reduction from the beginning of
the protocol), although lower effective population sizes could have contributed to this effect. We conclude that artificial
selection bolstered fitness, but only in the short-term, because the inadvertent fixation of extant genetic load later resulted
in pleiotropic fitness declines. Still, the short-term advantage of the selection protocol likely contributed to the success
of the speciation experiment since our recently-derived housefly populations are particularly vulnerable to inbreeding depression
effects on mating behavior. 相似文献
16.
We compare the results of four experiments, conducted at different times and with different protocols, that explored the relationship
between frequency-dependent selection and prey density in wild birds feeding on artificial populations of coloured baits.
One (experiment 4) used pastry baits that differed only in the presence or absence of a red stripe, and this experiment provided
no evidence for any kind of selective behaviour. The other three experiments used green and brown baits, and they all provided
evidence for a trend towards increasing anti-apostatic selection with high densities (>100 baits m–2). However, one of these (experiment 3) provided no evidence for frequency-dependent selection at low densities (0.5–20 baits
m–2), while the other two experiments concurred in suggesting a trend towards increasing apostatic selection with low densities
(down to 2 baits m–2). Together, these experiments both support and qualify the published findings of experiment 1 that frequency- dependent selection
by wild birds on bait populations is modified by density. Experiment 4 indicates that frequency-dependent selection may break
down entirely if bait types are too similar, while experiment 3 indicates that some details of this trend with density will
depend either on the protocol used or on exogenous changes in the birds’ feeding behaviour.
Received: 1 September 1999 / Accepted: 22 March 2000 相似文献
17.
L. N. Porokhovnik V. V. Viktorov N. A. Egolina T. G. Tsvetkova N. A. Lyapunova 《Russian Journal of Genetics》2011,47(12):1479-1486
Based on selective silver nitrate staining of active ribosomal gene (AcRG) clusters in nucleolus organizer regions (NORs)
of human metaphase chromosomes, a technique was developed earlier to estimate the AcRG dosage in individual genomes as a sum
of arbitrary units (0–3) ascribed to the silver precipitate (AgNOR) on ten NORs. The AcRG dosage was considered to be an additive
quantitative trait determined by five polymorphic autosomal loci (with four allelic forms for each locus). A database was
created to contain the data on AcRG cluster variants for more than 1000 individual human genomes. In this study, the population
frequencies of AcRG cluster variants were determined. The results agreed with the hypothesis that stabilizing selection acts
at the zygotic and/or early embryogenetic stage to restrain the AcRG genomic dosage (copy number) within a range from 14.9
to 23.7 arbitrary units (the cell is unviable when the trait is beyond this range). The average zygotic losses due to selection
were estimated at 9.1–9.9% for a real population. A computer model where the AcRG dosage of a progeny results from a random
combination of the AgNORs of the five acrocentric chromosome pairs of the parents was developed and used to simulate the formation
of a certain AcRG genomic dosage through generations in a human panmictic population with nonoverlapping generations. A combination
of stabilizing selection by total AcRG copy number and a certain spontaneous mutation rate (the probability of changes in
the cluster size of a NOR as a result of unequal crossingover in meiotic prophase) was shown to be a sufficient condition
for the restrain of equilibrium population frequencies of AgNOR size variants in a human panmictic population. Using the model,
the most probable spontaneous mutation frequency was predicted to be (2.1–2.3) × 10−2 per NOR per generation for human AgNORs. The predicted frequency was within the 95% confidence interval of the experimental
rate, which was determined by studying the inheritance of AgNOR variants in real families. 相似文献
18.
Restoration of mangrove plantations and colonisation by native species in Leizhou bay,South China 总被引:1,自引:0,他引:1
Hai Ren Shuguang Jian Hongfang Lu Qianmei Zhang Weijun Shen Weidong Han Zuoyun Yin Qinfeng Guo 《Ecological Research》2008,23(2):401-407
To examine the natural colonisation of native mangrove species into remediated exotic mangrove stands in Leizhou Bay, South
China, we compared soil physical–chemical properties, community structure and recruitments of barren mangrove areas, native
mangrove species plantations, and exotic mangrove species—Sonneratia apetala Buch.Ham—between plantations and natural forest. We found that severely degraded mangrove stands could not regenerate naturally
without human intervention due to severely altered local environments, whereas some native species had been recruited into
the 4–10 year S. apetala plantations. In the first 10 years, the exotic species S. apetala grew better than native species such as Rhizophora stylosa Griff and Kandelia candel (Linn.) Druce. The mangrove plantation gradually affected soil physical and chemical properties during its recovery. The
exotic S. apetala was more competitive than native species and its plantation was able to restore soil organic matter in about 14 years. Thus,
S. apetala can be considered as a pioneer species to improve degraded habitats to facilitate recolonisation by native mangrove species.
However, removal to control proliferation may be needed at late stages to facilitate growth of native species. To ensure sustainability
of mangroves in South China, the existing mangrove wetlands must be managed as an ecosystem, with long-term scientific monitoring
program in place. 相似文献
19.
R. S. Esipov K. A. Beirakhova L. A. Chupova V. G. Likhvantseva E. V. Stepanova A. I. Miroshnikov 《Russian Journal of Bioorganic Chemistry》2012,38(1):64-70
The pigment epithelium-derived factor (PEDF), a secreted 50 kDa glycoprotein, is one of the most potent endogenous inhibitors
of angiogenesis. The fragment 44–77 of PEDF possesses the antiangiogenic properties of the full-sized protein and is a potential
drug candidate for the treatment of diseases of visual organs accompanied by pathological neovascularization. An effective
biotechnological method for the large-scale production of the PEDF (44–77) fragment as part of the fusion protein with the
SspDnaB intein has been developed. The hybrid protein was produced in Escherichia coli bacterial cells in the form of inclusion bodies, solubilized, and subjected to autocatalytic cleavage with the release of
the PEDF (44–77) fragment (reaction yield 77%). The target peptide was separated from the intein by tangential ultrafiltration.
The final purification of PEDF (44–77) was performed by reversed-phase HPLC. The yield of the target peptide (purity 99%)
was 65 mg per 1 l of culture. The antiangiogenic activity of the peptide was confirmed in vitro using mouse endothelial cells
SVEC-4-10. It was found that the preparation at a concentration of 1 nM suppresses the proliferation of endothelial cells
by 53% and inhibits the formation of tube-like structures by endothelial cells. The ability of the recombinant PEDF (44–77)
to block the initial stages of angiogenesis was shown using an experimental model of rabbit corneal neovascularization. 相似文献
20.
Nahla S. Barakat 《AAPS PharmSciTech》2009,10(3):724-731
Rectal etodolac–Poloxamer gel systems composed of Poloxamer and bioadhesive polymers were developed and evaluated. Hydroxypropylmethyl
cellulose, poly)vinyl) pyrrolidone, methyl cellulose, hydroxyethylcellulose, and carbopol were examined as mucoadhesive polymers.
The characteristics of the rectal gels differed according to the properties of mucoadhesive polymers. The physicochemical
properties such as gelation temperature, gel strength, and bioadhesive force of various formulations were investigated. The
analysis of release mechanism showed that the release of etodolac was proportional to the square root of time, indicating
that etodolac might be released from the suppositories by Fickian diffusion. The anti-inflammatory effect of etodolac–Poloxamer
gel system was also studied in rats. Moreover, liquid suppository of etodolac did not cause any morphological damage to the
rectal tissues. These results suggested that in situ gelling liquid suppository with etodolac and mucoadhesive polymer was a physically safe, convenient, and effective rectal
dosage form for etodolac. 相似文献