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1.
Aim was to develop and optimize multiunit gastro-retentive floating beads (FBs) intended for localized and prolonged release of ginger for treating gastric ulcers. Protective effect of ginger extract (GE) against ulcer is well documented, but therapeutic use is compromised due to poor bioavailability and physicochemical properties. GE was only slightly soluble (3.19?±?0.38?mg/ml) in simulated gastric fluid (SGF; pH 1.2). The solubility decreased in water to 0.69?±?0.03?mg/ml and further by 26% in the presence of calcium carbonate (0.5% w/v). We prepared FBs of GE using calcium carbonate and sodium alginate in different proportions. Beads were evaluated for diameter, buoyancy, entrapment, and porosity. In vitro dissolution showed a Fickian release with a cumulative release of >80% at 24?h. Preclinical evaluation was done in cold-restraint stress induced gastric ulcers, in albino rats, in terms of (i) ulcer index, hemorrhagic streaks (l), mucus content, (ii) oxido-nitrosative stress, and (iii) histopathology. GE loaded FBs (200?mg/kg) were significantly better than free GE and better/equivalent to cimetidine (10?mg/kg). The system was evaluated for therapeutic effect (curative), i.e. after the induction of ulcers. Most of the natural phytochemical or antioxidants show pretreatment effectiveness. We, however, developed and established GE FBs for sustained curative effect.  相似文献   

2.
Colon targeting, as a site-specific delivery for oral formulation, remains a major challenge, especially for sensitive bioactive components such as therapeutic forms of phages, live attenuated virus and prebiotics–probiotics association. Synbiotics could be used to protect encapsulated probiotics during the gastrointestinal tract and control their release in the colon. To achieve these goals, effective prebiotics, such as inulin, could be combined with alginate – the most exploited polymer used for probiotic encapsulation – in the form of beads. This work aimed to study the biopharmaceutical behaviour of alginate beads (A) and inulin–alginate beads of different inulin concentrations (5 or 20%) in 2% alginate (AI5, AI20). Beads were loaded with three probiotic strains (Pediococcus acidilactici Ul5, Lactobacillus reuteri and Lactobacillus salivarius). Dissolution of beads was studied by USP4 under conditions simulating the gastrointestinal condition. The survival rates of the bacterial strains were measured by a specific qPCR bacterial count. Mucoadhesiveness of beads was studied by an ex vivo method using intestinal mucosa. To understand the behaviour of each formulation, the ultrastructure of the polymeric network was studied using scanning electron microscopy (SEM). Molecular interactions between alginate and inulin were studied by Fourier transform infra-red spectroscopy (FTIR). Dissolution results suggested that the presence of inulin in beads provided more protection for the tested bacterial strains against the acidic pH. AI5 was the most effective formulation to deliver probiotics to the colon simulation conditions. FTIR and SEM investigations explained the differences in behaviour of each formula. The developed symbiotic form provided a promising matrix for the development of colonic controlled release systems.  相似文献   

3.
The target site of action of probiotics is the intestine. They must be surviving the stomach acidic condition before reaching the target site. Three probiotic bacteria were microencapsulated in sodium alginate beads using a sophisticated microencapsulation technology provided by BÜCHI B-390. This study reports the tolerance of the different microencapsulated Lactobacillus at low pH using simulated gastric juice, comparing it with the tolerance of free bacteria. The three microencapsulated strains displayed time-dependent acid sensitivity at pH values under 3.0. At pH 2.0, a dramatic reduction in bacterial survival occurred after 5?min, with only L. casei surviving after 30?min, with 75% survival. At pH 2.5 microencapsulated L. casei survived for 90?, L. reuteri survived for 60?and L. bulgaricus survived for only 30?min, respectively. The microencapsulation technology used in this study may effectively protect Lactobacillus from gastric conditions and permit comparisons between strains.  相似文献   

4.
Abstract

Ginger extract (GE), a potential natural anticancer agent, has compromised therapeutic utilization due to poor bioavailability and physicochemical properties. Present study aimed at assigning GE with a pharmaceutical couture so as to improve its biopharmaceutical performance by monitoring its localized (though prolonged) delivery in the distal parts of gastrointestinal tract for the treatment of colon cancer. Alginate beads entrapping 85.9?±?1.78% GE were subjected to Eudragit S100 coating. Latter is insoluble at acidic and near neutral (6.8) pH of stomach and upper part of small intestine and it led to 50% retardation (upto 12?h) in release of GE. However, it was solubilised at pH?>?7.0 resulting in colon targeted system. Developed beads were free flowing, showed a particle size of 0.9?±?0.006?mm and super class-II release controlled by swelling and polymer relaxation. Preclinical evaluation using 1,2-dimethylhydrazine-induced colon cancer, in male Wistar rats, in terms of histopathology, oxidative stress, mitochondrial complex activity, β-glucuronidase and ammonia concentration determinations indicated GE loaded beads (50?mg/kg) to be significantly better (p?<?0.05) than free GE. Highlight of the study was that GE loaded coated alginate beads were administered after the induction of colon cancer and significant recession of the cancers was observed after 4 weeks of treatment.  相似文献   

5.
Oxidative stress is an important factor in drug induced hepatotoxicity and antioxidants from natural sources have potential to ameliorate it. The present study was aimed to investigate cyto-protective potential of probiotic Enterococcus lactis IITRHR1 (ElSN) and Lactobacillus acidophilus MTCC447 (LaSN) lysate against acetaminophen (APAP) induced hepatotoxicity. Cultured rat hepatocytes pretreated with ElSN/LaSN showed higher cell viability under APAP stress. Pre-treatment with ElSN, restored glutathione level and reduced ROS generation significantly which are major biomarkers of oxidative stress. It also reduced NO level, MDA formation and enhanced SOD activity. Pre-treatment with probiotic lysates significantly inhibited the translocation of pro-apoptotic protein (Bax), enhanced anti-apoptotic (Bcl-2) protein levels and prevented release of cyt c to cytosol; suggesting involvement of mitochondrial proteins in protection against APAP induced oxidative cellular damage. Loss in mitochondrial membrane potential due to APAP treatment was prevented in the presence of probiotic lysates. Protective action of ElSN/LaSN pretreatment was further supported by prevention of procaspase-3 activation, DNA fragmentation and chromatin condensation, in turn inhibiting APAP induced apoptotic cell death. The results indicate that probiotic preparations modulate crucial end points of oxidative stress induced apoptosis and may be used for management of drug induced liver injury.  相似文献   

6.
Background The intestinal permeability is increased in patients with diarrhoea‐predominant irritable bowel syndrome (D‐IBS). Aim To determine the possible efficacy of lactic acid bacteria on the increased intestinal permeability in D‐IBS. Methods Treatment was employed for 4 weeks in a randomized single blind placebo controlled study with 30 D‐IBS patients. Patients were given either probiotic fermented milk (Streptococcus thermophilus, Lactobacillus bulgaricus, Lactobacillus acidophilus and Bifidobacterium Longum) or milk beverage containing no bacteria. The clinical symptoms were scored and intestinal permeability was measured by a triple sugar test before and after treatment. Results Small bowel permeability was measured as the ratio of lactulose and mannitol recovery and colonic permeability was measured as the total mass of sucralose excretion (mg). After probiotics treatment, small bowel permeability decreased significantly from 0.038 (0.024) at baseline to 0.023 (0.020) (P = 0.004), the proportion of patients with increased small bowel permeability was lower than baseline (28.6% vs. 64.3%, P = 0.023). However, colonic permeability improved neither in the probiotics group nor in the placebo group at week 4. Treatment with probiotics significantly decreased the mean global IBS scores compared with the baseline scores (9.62 ± 1.05 vs. 7.64 ± 1.24, P < 0.001). Conclusion Short‐term active lactic acid bacteria treatment for D‐IBS improved mucosal barrier function.  相似文献   

7.
Celecoxib is a frequently used nonsteroidal anti-inflammatory drug (NSAID) in the treatment of rheumatoid arthritis and osteoarthritis. It selectively inhibits cyclooxygenase II (COX-2) enzyme which is responsible for the production of proinflammatory prostanoids. It has been proposed that since it does not significantly inhibit COX-1, an isoenzyme responsible for the production of cytoprotective prostanoids, celecoxib has fewer side effects in the stomach. Dipyrone which is a drug with potent analgesic activity has no significant inhibitory effect on COX. In this sudy, the effects of celecoxib and dipyrone on experimentally induced gastric ulcers in rats were compared with respect to different parameters. In the first experiment, in an attempt to identify the best dose for both drugs, a histamin-induced gastric ulcer model was used and each drug was administered at 5, 25 and 100 mg/kg doses, and ulcer index, acidity and mucus secretion were measured in the stomach. The best dose was determined to be 5 mg/kg for both drugs. Celecoxib was found to delay ulcer healing when compared to dipyrone especially when ulcer index was used as measure. In the second experiment, ulcer index, acidity, mucus secretion, and the levels of myeloperoxidase (MPO), lipid peroxide (MDA), non-protein sulfhydryl groups (NP-SH), and prostaglandin E2 (PGE2) were investigated in the stomach of rats with gastric ulcers induced by histamine, stresss and diethyldithiocarbamate (DDC). While celecoxib increased the ulcer index in stress-induced ulcer, dipyrone decreased the index in DDC-induced ulcer. Celecoxib also caused a significant increase of gastric mucus secretion in histamine-induced ulcer model. Gastric lipid peroxidation was significantly increased by dipyrone in the control group without gastric ulcer induction, whereas it was significantly increased by celecoxib in the histamine-induced and stress-induced ulcer groups. Dipyrone promoted a decrease in gastric NP-SH levels in the control group with stress-induced ulcer. With respect to gastric MPO activity, dipyrone caused a decrease in the histamine-induced ulcer group but it caused an increase in the stress-induced and DDC-induced ulcer groups. Gastric PGE2 levels in the control group without gastric ulcer induction were not affected by celecoxib while they were increased by dipyone. In conclusion, celecoxib prompted the formation of experimentally induced gastric ulcers more than did dipyrone. The study was supported by Osmangazi University Research Funds. Received 8 February 2007; revised 6 March 2007; accepted 13 April 2007  相似文献   

8.
The duodenal epithelium secretes bicarbonate at higher rates than does the stomach (or more distal small intestine) and the duodenal secretion is currently accepted as the most important defence mechanism against acid discharged from the stomach. HCO3 - entering the continuous layer of visco-elastic mucus gel on top of the epithelial surface maintains pH in its cell-facing portion at neutrality at acidities encountered in the healthy duodenum. The secretion is decreased in patients with acute and chronic duodenal ulcer disease and is inhibited by non-steroidal anti-inflammatory agents. Studies of the neurohumoral control of the duodenal alkaline secretion and of acid/base transport processes and intracellular signaling in duodenal enterocytes are currently of great research interest.  相似文献   

9.
In the present study, a simple and rapid method was developed to prepare a novel kind of inner-porous floating beads. The beads were prepared by dripping the foam solution into CaCl(2) solution using disposable syringe needle, where the foam solution consisting numerous of microbubbles with poloxamer 188 as foaming agents, alginate as foaming stablizer. Foamability and foam stability of different polymer ratios were evaluated. The SEM cross-section pictures of the beads showed that the beads were inner-porous and composed of bubbles with very thin wall bubbles stacked together. The visual observation result and the resultant-weight method confirmed that the floating beads showed good buoyancy, most beads could float in the stomach for more than 6 h. The floating beads release behavior in vitro showed that drug release from the beads in a sustained-release fashion for 10 h. Gamma scintigraphic images and pharmacokinetic studies in vivo showed that the beads can retained in the stomach for over 6 h and can improve the bioavailability of drug with narrow absorption window.  相似文献   

10.
Prebiotics are used to influence the growth, colonization, survival, and activity of probiotics, and enhance the innate immunity, thus improving the health status of the host. The survival, growth, and activity of probiotics are often interfered with by intrinsic factors and indigenous microbes in the gastrointestinal tract. In this study, Bulnesia sarmienti aqueous extract (BSAE) was evaluated for the growth-promoting activity of different strains of Lactobacillus acidophilus, and a simple, precise, cost-effective high-performance liquid chromatography (HPLC) method was developed and validated for the determination of active prebiotic ingredients in the extract. Different strains of L. acidophilus (probiotic) were incubated in de Man, Rogosa, and Sharpe (MRS) medium with the supplementation of BSAE in a final concentration of 0.0%, 1.0%, and 3.0% (w/v) as the sole carbon source. Growth of the probiotics was determined by measuring the pH changes and colony-forming units (CFU/mL) using the microdilution method for a period of 24 hours. The HPLC method was designed by optimizing mobile-phase composition, flow rate, column temperature, and detection wavelength. The method was validated according to the requirements of a new method, including accuracy, precision, linearity, limit of detection, limit of quantitation, and specificity. The major prebiotic active ingredients in BSAE were determined using the validated HPLC method. The rapid growth rate of different strains of L. acidophilus was observed in growth media with BSAE, whereas the decline of pH values of cultures varied in different strains of probiotics depending on the time of culture. (+)-Catechin and (−)-epicatechin were identified on the basis of their retention time, absorbance spectrum, and mass spectrometry fragmentation pattern. The developed method met the limit of all validation parameters. The prebiotic active components, (+)-catechin and (−)-epicatechin, were quantified as 1.27% and 0.71% (w/w), respectively, in crude extract, and 6.36 ± 0.06 μg/ mL and 4.47 ± 0.41 μg/mL (mean ± standard deviation), respectively, in a prebiotic capsule of BSAE by HPLC analysis. BSAE contains the active components of prebiotics and enhances the growth of L. acidophilus.  相似文献   

11.
《Drug delivery》2013,20(1):94-99
Abstract

Background: Acetic acid ulcerative colitis (UC) is an experimental condition created due to intra-rectal administration of acetic acid which causes inflammation and ulceration in the lining of colon and rectum. In such condition, the colon cannot absorb liquid from the stools, resulting in larger volume of watery stools. Mesalazine is mainly used for the treatment of UC but suffers from the drawback of having poor bioavailability. UC is also characterized by alteration in colonic microflora. The present work was focused on delivering mesalazine along with probiotic, which would facilitate to refurbish customary growth of microflora. Mesalazine and probiotic were encapsulated in pectin beads with an aim to protect the drug from gastric environment and target to colonic region.

Methods: Pectin beads were prepared, formulation process was optimized for polymer concentration, drug concentration, cross-linking agent concentration. Formulation was characterized for surface morphology, in vitro drug release studies, determination of viable cell count, in vivo ulcer protective studies and stability studies.

Results: Average particle diameter of beads was ~1.44–1.72?mm. Drug entrapment efficiency was found to be optimal (78–79%). A sustained release of drug was observed for 5?h; nearly 60% of drug was released at the end of 10?h. Microbiological studies of probiotic showed best cell viability. In acetic acid induced UC model, Mesalazine–probiotic beads-treated group showed significant (p?<?0.01) ulcer protection index with respect to free drug-treated group.

Conclusion: In conclusion, mesalazine–probiotic loaded beads may serve as a useful colon specific drug delivery system for treatment of colitis.  相似文献   

12.
Abstract

The present study aimed to optimise the microencapsulation of Lactobacillus acidophilus La-05 by spray drying, using soy extract and maltodextrin as encapsulants. Air inlet temperature, maltodextrin/soy extract ratio and feed flow rate were investigated through Central Composite Rotational Design (CCRD). Probiotic viability increased with increasing the proportion of soy extract. Temperature and feed flow rate had a negative effect. Particle diameter ranged from 4.97 to 8.82?μm, water activity from 0.25 to 0.52 and moisture from 2.30 to 7.01?g.100g?1 Particles produced following the optimised conditions (air temperature of 87?°C, maltodextrin/soy extract ratio of 2:3 w.w?1, feed flow rate of 0.54?L.h?1) reached Encapsulation yield (EY) of 83%. Thermogravimetry and FTIR analysis suggested that microcapsules could protect L. acidophilus cells against dehydration and heating. During storage, microencapsulated probiotic had high cell viability (reductions ranged between 0.12 and 1.72 log cycles). Soy extract/maltodextrin presented well-encapsulating properties of Lactobacillus acidophilus La-05.  相似文献   

13.
Citrus pectin enzyme hydrolysate (PEH) of different hydrolysis time intervals (6 hours, PEH-6; 12 hours, PEH-12; 24 hours, PEH-24; or 48 hours, PEH-48) or concentrations (1%, 2%, and 4%) was tested for its growth stimulation effect on two probiotics, Bifidobacterium bifidum and Lactobacillus acidophilus. Higher monosaccharide concentrations and smaller molecular weights of PEHs were obtained by prolonging the hydrolysis time. In addition, higher PEH concentrations resulted in significantly higher (p < 0.05) probiotic populations, pH reduction, and increase in total titratable acidity than the glucose-free MRS negative control. Furthermore, significantly higher populations in the low pH environment and longer survival time in nonfat milk (p < 0.05) were observed when the two probiotics were incubated in media supplemented with 2% PEH-24, than in glucose and the negative control. In comparison with other prebiotics, addition of 2% PEH-24 resulted in a more significant increase in the probiotic population (p < 0.05) than in the commercial prebiotics. This study demonstrated that PEH derived from citrus pectin could be an effective prebiotic to enhance the growth, fermentation, acid tolerance, and survival in nonfat milk for the tested probiotics.  相似文献   

14.
  1. Probiotics are live microorganisms claimed to exert beneficial effects on the host. This study investigated their effect on the metabolism and pharmacokinetics of sulfasalazine (SSZ), a drug whose efficacy depends on metabolism by azoreductase (AR) in the gut microbiota to sulfapyridine (SP) and 5-acetylsalicylic acid (5-ASA).

  2. The probiotic strains Lactobacillus acidophilus L10, Bifidobacterium lactis B94 and Streptococcus salivarius K12 possessed AR activity and a corresponding ability to metabolize SSZ.

  3. Treatment of male Wistar rats (n = 5) with oral 2 g doses of a mixture of the three probiotics (total dose 1.8 × 109 cfu) every 12 h for 3 days resulted in a significant increase (p < 0.05) in AR activity in ex vivo colon contents with a corresponding increase in SSZ metabolism.

  4. Similar probiotic treatment of male Wistar rats (n = 8) followed by an oral 100 mg/kg dose of SSZ produced high plasma levels of SP, but pharmacokinetic parameters of SSZ and SP were not significantly different from control rats given SSZ.

  5. These results indicate that probiotic strains possess AR activity and can metabolize SSZ. Treatment with probiotics increases AR activity in the gut microbiota but has no effect on plasma levels of SSZ and SP following a subsequent oral dose of SSZ.

  相似文献   

15.
This work aims to develop an encapsulated oral-synbiotic supplement by studying the effect of adding inulin in alginate beads and observing its ability to protect three probiotic strains: Pediocucus acidilactici, Lactobacillus reuteri and Lactobacillus salivarius. Beads of different inulin concentrations 0%, 5%, 10%, 15% and 20% (w/v) in 2% (w/v) alginate solution were prepared by the extrusion/ionotropic gelation method. Polymer distribution within beads was characterised using confocal laser scanning microscopy. Interactions between alginate and inulin were monitored by Fourier transform infra-red spectroscopy (FTIR). Effect of encapsulation on viability, antimicrobial ability, acid tolerance and bile tolerance of probiotic strains were investigated. Antimicrobial and probiotic properties of bacterial strains were not affected by encapsulation. Bacterial protection against acidity was increased by adding inulin. Beads with 5% w/v inulin were the most effective in bacterial protection against bile-salts. To our knowledge, this work is the first to use such high concentrations of inulin.  相似文献   

16.
Probiotics are bacteria that are commercially available as dietary supplements. One of the important properties of probiotics is their ability to survive in the intestine. Recent evidence has identified kynurenic acid (KYNA) as a bactericidal constituent of intestinal fluid. These data led us to study the influence of KYNA on the viability of selected probiotics. We found that KYNA supported the growth of bacteria in the probiotics Acidolac (Lactobacillus acidophilus, Bifidobacterium) and Lakcid Forte (Lactobacillus rhamnosus) or retarded the growth of bacteria from the Acidolac, BioGaia (Lactobacillus reuteri Protectis), Dicoflor (Lactobacillus rhamnosus GG), Lacium (Lactobacillus plantarum) and Trilac (Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium animalis subsp. lactis) probiotics depending on its concentration. KYNA did not affect the viability of bacteria from the probiotic Linex (Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12). Our results suggest a potential role of KYNA in the regulation of bacterial growth in the digestive system.  相似文献   

17.
Abstract

Lactobacillus acidophilus LA-5 has poor survivability in yoghurts. This study aims to microencapsulate L. acidophilus LA-5 using polymerised whey protein as wall material and evaluate its survivability and effects on physiochemical properties of yoghurts. The microencapsulation yield was 92.90% and average beads size was 744?μm. Microencapsulated L. acidophilus LA-5 showed higher survival at simulated gastrointestinal conditions. Microencapsulated L. acidophilus LA-5 had improved survivability (~106 cfu/mL) than free cells (~104 cfu/mL) after digesting by simulated intestinal juice (6?h) in yoghurts during 10-week storage. Microencapsulated L. acidophilus LA-5 improved the firmness and protein content and decreased the spontaneous whey separation and synaeresis of yoghurts significantly (p?<?0.01). Changes in pH and free microorganism population of yoghurts during storage were not affected by adding microencapsulated L. acidophilus LA-5. Microencapsulation of L. acidophilus LA-5 using polymerised whey protein as wall material improved its survivability and the physiochemical properties of the yoghurt.  相似文献   

18.
目的:研究胃甘胶囊对实验性胃溃疡的作用.方法:采用水浸应激性、利血平型、幽门结扎型及乙酸型胃溃疡模型研究胃甘胶囊抗胃溃疡作用;以幽门结扎收集胃液观察对胃液分泌的影响.结果:胃甘胶囊对小鼠水浸应激性、利血平型及大鼠幽门结扎型胃溃疡均有明显的保护作用;对大鼠乙酸型胃溃疡有明显的促进愈合作用;能抑制大鼠胃酸的分泌并促进胃粘液分泌.结论:胃甘胶囊有抑制实验性胃溃疡的作用,该作用可能与其抑制胃酸分泌、促进胃粘液分泌有关.  相似文献   

19.
彭钧  操电群  李小月 《安徽医药》2008,12(10):895-897
目的探讨高良姜超临界萃取物(GLJ)对应激性胃溃疡模型溃疡形成及胃液分泌、血清胃泌素(GAS)和胃黏膜生长抑素(SS)的影响。方法以束缚-水浸应激性胃溃疡大鼠为对象,探讨GLJ对大鼠溃疡指数及胃液分泌、胃蛋白酶活性、血清胃泌素(GAS)和胃黏膜生长抑素(SS)水平的影响。结果GLJ能降低束缚-水浸应激性溃疡大鼠的溃疡指数,并可使该模型大鼠胃液分泌量、血清GAS水平和胃蛋白酶活性降低,胃黏膜SS水平明显回升,接近正常水平。结论GLJ能降低束缚-水浸应激性胃溃疡的形成,对此模型胃液分泌、血清GAS、胃黏膜SS水平有一定的调节功能,可能是其抗溃疡作用的机制之一。  相似文献   

20.
本文观察了莨菪类药物(东茛菪碱、樟柳碱、山茛菪碱)对大鼠三种实验性胃溃疡的影响,并对其作用机制进行了初步的探讨。结果表明:莨菪类药物有对抗大鼠应激性胃溃疡、药物性胃溃疡及慢性胃溃疡的作用,且有量效依赖关系;对胃液和血液等各项生化指标分析表明,这类药物有抑制胃酸分泌、降低胃蛋白酶活性、增强胃粘液屏障,提高血清胃泌素浓度的作用。提示这些结果可能与其抗溃疡效应有关。  相似文献   

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