共查询到20条相似文献,搜索用时 15 毫秒
1.
Alginate-based oral drug delivery system for tuberculosis: pharmacokinetics and therapeutic effects 总被引:5,自引:0,他引:5
Qurrat-ul-Ain Sharma S Khuller GK Garg SK 《The Journal of antimicrobial chemotherapy》2003,51(4):931-938
Alginate microparticles were developed as oral sustained delivery carriers for antitubercular drugs in order to improve patient compliance. In the present study, pharmacokinetics and therapeutic effects of alginate microparticle encapsulated antitubercular drugs, i.e. isoniazid, rifampicin and pyrazinamide were examined in guinea pigs. Alginate microparticles containing antitubercular drugs were evaluated for in vitro and in vivo release profiles. These microparticles exhibited sustained release of isoniazid, rifampicin and pyrazinamide for 3-5 days in plasma and up to 9 days in organs. Peak plasma concentration (Cmax), Tmax, elimination half-life (t1/2e) and AUC0- infinity of alginate drugs were significantly higher than those of free drugs. The encapsulation of drug in alginate microparticles resulted in up to a nine-fold increase in relative bioavailability compared with free drugs. Chemotherapeutic efficacy of alginate drug microspheres against experimental tuberculosis showed no detectable cfu values at 1:100 and 1:1000 dilutions of spleen and lung homogenates. Histopathological studies further substantiated these observations, thus suggesting that application of alginate-encapsulated drugs could be useful in the effective treatment of tuberculosis. 相似文献
2.
New biodegradable polymers for injectable drug delivery systems. 总被引:11,自引:0,他引:11
Many biodegradable polymers were used for drug delivery and some are successful for human application. There remains fabrication problems, such as difficult processability and limited organic solvent and irreproducible drug release kinetics. New star-shaped block copolymers, of which the typical molecular architecture is presented, results from their distinct solution properties, thermal properties and morphology. Their unique physical properties are due to the three-dimensional, hyperbranched molecular architecture and influence microsphere fabrication, drug release and degradation profiles. We recently synthesized thermosensitive biodegradable hydrogel consisting of polyethylene oxide and poly(L-lactic acid). Aqueous solution of these copolymers with proper combination of molecular weights exhibit temperature-dependent reversible sol-gel transition. Desired molecular arrangements provide unique behavior that sol (at low temperature) form gel (at body temperature). The use of these two biodegradable polymers have great advantages for sustained injectable drug delivery systems. The formulation is simple, which is totally free of organic solvent. In sol or aqueous solution state of this polymer solubilized hydrophobic drugs prior to form gel matrix. 相似文献
3.
The effect of Pluronic on the protein release kinetics of an injectable drug delivery system. 总被引:6,自引:0,他引:6
A new class of injectable controlled release depots has been prepared by incorporating materials that preferentially segregate during phase inversion. These consist of blends of poly(ethylene oxide) (PEO)/poly(propylene oxide) (PPO)/poly(ethylene oxide) (PEO) triblock copolymers (Pluronics) with poly(D,L-lactide) (PDLA)/1-methyl-2-pyrrolidinone (NMP) solutions. The effects of preferential segregation on the phase inversion dynamics and in vitro protein release kinetics were examined using dark ground imaging, high performance liquid chromatography (HPLC), scanning electron microscopy (SEM), and confocal microscopy. Variations in Pluronic concentration and molecular weight had an insignificant effect on the internal depot morphologies, however, increasing the concentration and molecular weight did result in increased phase separation rates and, surprisingly, a decrease in the magnitude of the protein burst, though the release profiles still retained a typical burst-type shape. Additionally, increasing the Pluronic concentration beyond a critical point resulted in a transition from a burst-type profile to an extended-release profile. An interpretation of these results in terms of a qualitative model for the protein release mechanism is also given. 相似文献
4.
J W Schaffner S Alleman P Ludwig-Beymer J Muzynski D J King L J Pacura 《The Journal of nursing administration》1999,29(9):43-50
An integrated healthcare delivery system requires a consistent patient care delivery model. The authors describe the process used to define common elements of the patient care model. These elements include the roles of chief nurse executives, first-line managers, staff registered nurses, and unlicensed assistive personnel. In addition, the philosophy of nursing and support functions (staff education and nursing dashboard for quality measurement) in place across the system are discussed. 相似文献
5.
Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. 总被引:22,自引:0,他引:22
In recent years scientific and technological advancements have been made in the research and development of rate-controlled oral drug delivery systems by overcoming physiological adversities, such as short gastric residence times (GRT) and unpredictable gastric emptying times (GET). Several approaches are currently utilized in the prolongation of the GRT, including floating drug delivery systems (FDDS), also known as hydrodynamically balanced systems (HBS), swelling and expanding systems, polymeric bioadhesive systems, modified-shape systems, high-density systems, and other delayed gastric emptying devices. In this review, the current technological developments of FDDS including patented delivery systems and marketed products, and their advantages and future potential for oral controlled drug delivery are discussed. 相似文献
6.
In vitro and in vivo evaluation of an oral system for time and/or site-specific drug delivery. 总被引:11,自引:0,他引:11
M E Sangalli A Maroni L Zema C Busetti F Giordano A Gazzaniga 《Journal of controlled release》2001,73(1):103-110
Aim of this work was the evaluation of an oral system (Chronotopic) designed to achieve time and/or site-specific release. The system consists in a drug-containing core, coated by a hydrophilic swellable polymer which is responsible for a lag phase in the onset of release. In addition, through the application of an outer gastroresistant film, the variability in gastric emptying time can be overcome and a colon-specific release can be sought relying on the relative reproducibility of small intestinal transit time. For this study, cores containing antipyrine as the model drug were prepared by tableting and both the retarding and enteric coatings were applied in fluid bed. The release tests were carried out in a USP 24 paddle apparatus. The in vivo testing, performed on healthy volunteers, envisaged the HPLC determination of antipyrine salivary concentration and a gamma-scintigraphic investigation. The in vitro release curves presented a lag phase preceding drug release and the in vivo pharmacokinetic data showed a lag time prior to the detection of model drug in saliva. Both in vitro and in vivo lag times correlate well with the applied amount of the hydrophilic retarding polymer. The gamma-scintigraphic study pointed out that the break-up of the units occurred in the colon. The obtained results showed the capability of the system in delaying drug release for a programmable period of time and the possibility of exploiting such delay to attain colon-targeted delivery according to a time-dependent approach. 相似文献
7.
A new oral sustained-release (SR) drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer (CP) has been proposed. This swelling polymer incorporation layer system, referred to as SPILA system, consists of core granules coated with a mixture of CP, water insoluble polymer, and water-soluble polymer (WP). Release profiles of metoprolol tartrate (ME) from SPILA system were pH dependent: drug release was slower in the medium of pH 1.2 than in the medium of pH 6.8 due to a coating layer with pH-dependent swelling polymer, CP. Lower C(max), longer T(max), longer MRT and higher AUC values were obtained following administration of SR granules based on SPILA system to beagle dogs compared with pH-independent SR granules having a coating layer without CP, while both SR granules provided similar in vitro release profiles. Moreover, using morphine hydrochloride (MO), in vitro and in vivo performances of the SPILA system were investigated. pH-dependency on the release profiles of MO from SPILA system was more evident when the amount of CP incorporated in SPILA system was increased. AUC and MRT values following administration of SR granules of MO with a coating layer containing 8% of CP to beagle dogs were 191 ng h/mL and 10.6 h respectively, while those following SR granules of MO with a coating layer containing 1% of CP to beagle dogs were 86.4 ng h/mL and 5.86 h, respectively. An important role of CP in the release-regulating layer of SPILA system for keeping the higher and more extended plasma levels of morphine free base was confirmed from the in vivo performance of SPILA system. 相似文献
8.
M Lodzki B Godin L Rakou R Mechoulam R Gallily E Touitou 《Journal of controlled release》2003,93(3):377-387
Cannabidiol (CBD) is a new drug candidate for treatment of rheumatic diseases. However, its oral administration is associated with a number of drawbacks. The objective of this study was to design a transdermal delivery system for CBD by using ethosomal carriers. CBD ethosomes were characterized by transmission electron microscopy, confocal laser scanning microscopy and differential scanning calorimetry. Results indicated that CBD and phosphatidylcholine form an eutectic mixture. In vivo application of ethosomal CBD to CDI nude mice produced a significant accumulation of the drug in the skin and in the underlying muscle. Upon transdermal application of the ethosomal system to the abdomen of ICR mice for 72 h, steady-state levels were reached at about 24 h and lasted at least until the end of the experiment, at 72 h. Furthermore, transdermal application of ethosomal CBD prevented the inflammation and edema induced by sub-plantar injection of carrageenan in the same animal model. In conclusion, ethosomes enable CBD's skin permeation and its accumulation in a depot at levels that demonstrate the potential of transdermal CBD to be used as an anti-inflammatory treatment. 相似文献
9.
S P Klemens C A Sharpe M C Rogge M H Cynamon 《Antimicrobial agents and chemotherapy》1994,38(7):1476-1479
The activity of levofloxacin (LEV) was evaluated in a murine model of tuberculosis. Approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 were given intravenously to 4-week-old female outbred mice. In a dose-response study, treatment with LEV at 100, 200, and 400 mg/kg of body weight was started 1 day after infection and was given daily for 28 days. Viable cell counts were determined from homogenates of spleens and lungs. A dose-related reduction in organism cell counts in organs was noted for LEV. The activities of LEV at 100, 200, and 300 mg/kg were compared with those of first-line antituberculosis agents. Both isoniazid and rifampin were more active than LEV. There was no difference in activity between LEV and either ethambutol or pyrazinamide against splenic organisms. The activities of ethambutol and LEV at the two higher doses were comparable against lung organisms. LEV at 300 mg/kg was more active than pyrazinamide against lung organisms. The activity of LEV was compared with those of two other quinolones, ofloxacin and sparfloxacin. LEV at 200 mg/kg had more than twofold greater activity than ofloxacin at the same dose. Sparfloxacin at 100 mg/kg was more active than LEV at 200 mg/kg; however, the activities of sparfloxacin at 50 mg/kg and LEV at 200 mg/kg were comparable. The promising activity of LEV in M. tuberculosis-infected mice suggests that it is a good candidate for clinical development as a new antituberculosis agent. 相似文献
10.
Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis for more than a decade. The high incidence and severity of side effects, which are dose-related and associated with long-term administration, have limited its use. This has led to the search for new delivery systems which can overcome the side effects by controlling the drug release. In this study, Indomethacin Extended Release Formulation was developed by pelletization using the method of extrusion/spheronization. The drug containing pellets were further coated to achieve the required release profile as per USP. Coating systems developed on the principle of microporous membrane drug delivery using soluble salt gave the best results. 相似文献
11.
A model is developed to describe protein release kinetics from injectable, polymer solution depots which undergo rapid phase inversion on injection. The model consists of a polymer-rich phase and a solvent-rich phase, consistent with experimentally observed phase inversion morphology. Equations in the polymer-rich phase are based on diffusion-reaction mass balances for solvent, water and dissolved drug, and the rate of dissolution of dispersed drug particles. Equations in the water-rich phase are also of the diffusion-reaction type. Transport parameters in the polymer-rich phase are coupled to the ternary thermodynamics through friction formalism, and remaining parameters are estimated from literature data, leaving two free parameters: volume fraction of water-rich phase (epsilon) and k, the mass-transfer coefficient for bath-side transfer of the protein. Variations of these parameters lead to predictions of release profiles that vary from a rapid, burst-like behavior followed by a locking-in of the polymer-rich phase, to a uniform, zero-order profile. Comparisons are made to lysozyme release data for three systems: PLGA solutions in N-methlypyrollidinone (NMP), PLA solutions in NMP, and the latter with added Pluronic. Good agreement between model predictions and data is shown; in particular, the transition from rapid release to zero-order kinetics that occurs on addition of Pluronic is illustrated. 相似文献
12.
Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors. 总被引:7,自引:0,他引:7
Joshua Williams Rachael Lansdown Robert Sweitzer Marek Romanowski Rachel LaBell Rajan Ramaswami Evan Unger 《Journal of controlled release》2003,91(1-2):167-172
Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar in a mouse xenograft tumor model. 相似文献
13.
J Salonen L Laitinen A M Kaukonen J Tuura M Bj?rkqvist T Heikkil? K V?h?-Heikkil? J Hirvonen V-P Lehto 《Journal of controlled release》2005,108(2-3):362-374
Mesoporous silicon (PSi) microparticles were produced using thermal carbonization (TCPSi) or thermal oxidation (TOPSi) to obtain surfaces suitable for oral drug administration applications. The loading of five model drugs (antipyrine, ibuprofen, griseofulvin, ranitidine and furosemide) into the microparticles and their subsequent release behaviour were studied. Loading of drugs into TCPSi and TOPSi microparticles showed, that in addition to effects regarding the stability of the particles in the presence of aqueous or organic solvents, surface properties will affect compound affinity towards the particle. In addition to the surface properties, the chemical nature of the drug and the loading solution seems to be critical to the loading process. This was reflected in the obtained loading efficiencies, which varied between 9% and 45% with TCPSi particles. The release rate of a loaded drug from TCPSi microparticles was found to depend on the characteristic dissolution behaviour of the drug substance. When the dissolution rate of the free/unloaded drug was high, the microparticles caused a delayed release. However, with poorly dissolving drugs, the loading into the mesoporous microparticles clearly improved dissolution. In addition, pH dependency of the dissolution was reduced when the drug substance was loaded into the microparticles. 相似文献
14.
Pandey R Sharma A Zahoor A Sharma S Khuller GK Prasad B 《The Journal of antimicrobial chemotherapy》2003,52(6):981-986
OBJECTIVES: To improve the bioavailability of antitubercular drugs (ATDs) as well as to assess the feasibility of administering ATDs via the respiratory route, this study reports the formulation of three frontline ATDs, i.e. rifampicin, isoniazid and pyrazinamide encapsulated in poly (DL-lactide-co-glycolide) nanoparticles suitable for nebulization. METHODS: Drug-loaded nanoparticles were prepared by the multiple emulsion technique, vacuum-dried and nebulized to guinea pigs. The formulation was evaluated with respect to the pharmacokinetics of each drug and its chemotherapeutic potential in Mycobacterium tuberculosis infected guinea pigs. RESULTS: The aerosolized particles exhibited a mass median aerodynamic diameter of 1.88 +/- 0.11 microm, favourable for bronchoalveolar lung delivery. A single nebulization to guinea pigs resulted in sustained therapeutic drug levels in the plasma for 6-8 days and in the lungs for up to 11 days. The elimination half-life and mean residence time of the drugs were significantly prolonged compared to when the parent drugs were administered orally, resulting in an enhanced relative bioavailability (compared to oral administration) for encapsulated drugs (12.7-, 32.8- and 14.7-fold for rifampicin, isoniazid and pyrazinamide, respectively). The absolute bioavailability [compared to intravenous (i.v.) administration] was also increased by 6.5-, 19.1- and 13.4-fold for rifampicin, isoniazid and pyrazinamide, respectively. On nebulization of nanoparticles containing drugs to M. tuberculosis infected guinea pigs at every 10th day, no tubercle bacilli could be detected in the lung after five doses of treatment whereas 46 daily doses of orally administered drug were required to obtain an equivalent therapeutic benefit. CONCLUSIONS: Nebulization of nanoparticles-based ATDs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary tuberculosis. 相似文献
15.
Bioadhesive microdevices with multiple reservoirs: a new platform for oral drug delivery. 总被引:6,自引:0,他引:6
A variety of delivery systems have been devised, in recent years, to improve the oral bioavailability of drugs including enterically coated tablets, capsules, particles, and liposomes. Microfabrication technology may offer some potential advantages over conventional drug delivery technologies. This technology, combined with appropriate surface chemistry, may permit the highly localized and unidirectional release of drugs, permeation enhancers, and/or promoters. In this study, we demonstrate the fabrication of prototype reservoir-containing microdevices and a surface chemistry protocol that can be used to bind lectin via avidin-biotin interactions to these micromachined drug delivery vehicles. The use of microfabrication allows one to tailor the size, shape, reservoir volume, and surface characteristics of the drug delivery vehicle. In vitro studies show enhanced bioadhesion of these lectin conjugated silicon microdevices. This approach may be used to improve the absorption of pharmacologically active biopolymers such as peptides, proteins and oligonucleotides into circulation at targeted sites in the GI system via the creation of a robust hybrid organic/inorganic delivery system. This paper describes one of the first applications of microfabrication to oral drug delivery. 相似文献
16.
Development of a multifunctional matrix drug delivery system surrounded by an impermeable cylinder. 总被引:5,自引:0,他引:5
A multifunctional drug delivery system based on hydroxypropyl methylcellulose (HPMC)-matrices (tablets) placed within an impermeable polymeric cylinder (open at both ends) was developed. Depending on the configuration of the device, extended release, floating or pulsatile drug delivery systems could be obtained. The release behaviour of the different devices was investigated as a function of HPMC viscosity grade, HPMC content, type of drug (chlorpheniramine maleate or ibuprofen), matrix weight, position of the matrix within the polymeric cylinder, addition of various fillers (lactose, dibasic calcium phosphate or microcrystalline cellulose) and agitation rate of the release medium. The drug release increased with a reduced HPMC viscosity grade, higher aqueous drug solubility, decreased HPMC content and increased surface area of the matrix. The release was fairly independent of the agitation rate, the position of the tablet within the polymeric cylinder and the length of the cylinder. With the pulsatile device, the lag time prior to the drug release could be controlled through the erosion rate of the matrix (matrix weight and composition). 相似文献
17.
A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached. 相似文献
18.
Nakase H Okazaki K Tabata Y Uose S Ohana M Uchida K Matsushima Y Kawanami C Oshima C Ikada Y Chiba T 《The Journal of pharmacology and experimental therapeutics》2000,292(1):15-21
Several studies have indicated the involvement of macrophages and dendritic cells in active inflammatory bowel disease (IBD). Manipulation of these cells is considered a very important therapeutic strategy for patients with IBD. We evaluated the effect of a new drug delivery system targeting microfold cells and macrophages with poly(DL-lactic acid) microspheres containing dexamethasone (Dx). Colitis was induced in BALB/c mice by 5% dextran sodium sulfate. Dx microspheres (n = 10) and only Dx (n = 10) were orally administered to dextran sodium sulfate-treated mice. Thereafter, serum levels and tissue distributions of Dx were investigated. To estimate the efficacy of this drug delivery system, we measured the histological score, myeloperoxidase activity and nitric oxide production, and gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma in the colonic tissue. Serum Dx levels were not increased after oral administration of Dx microspheres. The tissue distribution of microspheres containing (125)I-labeled Dx in inflamed colon was significantly higher than in other organs. The histological score, myeloperoxidase activity, and nitric oxide production of the group treated with Dx microspheres were significantly lower than of those treated with Dx alone. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in mice treated with Dx microspheres. Microspheres containing glucocorticoids such as Dx, which target microfold cells and macrophages, can facilitate mucosal repair in experimental colitis and could be an ideal agent for treatment of human IBD. 相似文献
19.
Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. 总被引:21,自引:0,他引:21
The oral delivery of hydrophobic drugs presents a major challenge because of the low aqueous solubility of such compounds. Self-emulsifying drug delivery systems (SEDDS), which are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. SEDDS can be orally administered in soft or hard gelatin capsules and form fine relatively stable oil-in-water (o/w) emulsions upon aqueous dilution owing to the gentle agitation of the gastrointestinal fluids. The efficiency of oral absorption of the drug compound from the SEDDS depends on many formulation-related parameters, such as surfactant concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and charge, all of which in essence determine the self-emulsification ability. Thus, only very specific pharmaceutical excipient combinations will lead to efficient self-emulsifying systems. Although many studies have been carried out, there are few drug products on the pharmaceutical market formulated as SEDDS confirming the difficulty of formulating hydrophobic drug compounds into such formulations. At present, there are four drug products, Sandimmune and Sandimmun Neoral (cyclosporin A), Norvir (ritonavir), and Fortovase (saquinavir) on the pharmaceutical market, the active compounds of which have been formulated into specific SEDDS. Significant improvement in the oral bioavailability of these drug compounds has been demonstrated for each case. The fact that almost 40% of the new drug compounds are hydrophobic in nature implies that studies with SEDDS will continue, and more drug compounds formulated as SEDDS will reach the pharmaceutical market in the future. 相似文献
20.
Thiolated chitosans: development and in vitro evaluation of a mucoadhesive, permeation enhancing oral drug delivery system. 总被引:7,自引:0,他引:7
Andreas Bernkop-Schnürch Davide Guggi Yvonne Pinter 《Journal of controlled release》2004,94(1):177-186
It was the aim of this study to develop a mucoadhesive, permeation enhancing delivery system for orally administered poorly absorbed drugs. Chitosan was modified by the immobilisation of thiol groups utilising 2-iminothiolane (Traut's reagent). The permeation enhancing effect of the resulting chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) in combination with the permeation mediator glutathione (GSH) was evaluated in Ussing chambers on freshly excised small intestinal mucosa from guinea pigs using rhodamine 123 as marker for passive drug uptake. The mucoadhesive properties of the chitosan-TBA conjugate adjusted to pH 3, 5 and 7 were evaluated via the rotating cylinder method and via tensile studies. Release studies were performed with tablets comprising 10% cefadroxil used as model drug, 10% GSH and 80% chitosan-TBA conjugate pH 3 in 100 mM phosphate buffer pH 6.8 at 37 degrees C. Results showed a 3-fold higher permeation enhancing effect of the chitosan-TBA conjugate/GSH system in comparison to unmodified chitosan. Mucoadhesion studies revealed that the lower the pH of the thiolated chitosan is, the higher are its mucoadhesive properties. Release studies showed a sustained release of both cefadroxil and GSH over several hours. This delivery system might represent a promising novel tool in order to improve the therapeutic efficacy of various drugs which are poorly absorbed from the gastrointestinal tract. 相似文献