Insights into the Structure of Sucralfate by Advanced Solid- and Liquid-State NMR.

Sucralfate, which is a sucrose octasulfate aluminum complex, is an active pharmaceutical ingredient (API) falling in the category of cytoprotective agents which are very effective for gastric and duodenal ulcers. On interaction with stomach acid, it ionizes into aluminum and sucrose octasulfate ions to form a protective layer over the ulcerated region inhibiting further attack from acid. The mechanism of action of sucralfate in the context of its structure is not well understood. Considering that at least two forms of this API are available in the market, there are no reports on the various forms of sucralfate and differences in their pharmacological action. We characterized the two forms of sucralfate using multinuclear, multidimensional solid-state NMR, and the results show significant structural differences between them arising from variation in the aluminum environment and the level of hydration. The impact of structural differences on pharmacological action was examined by studying acid-induced Al release by 27Al liquid-state NMR. The sucralfate, European pharmaceutical standard, Form I, undergoes faster disruption in acid compared to Form II. The difference is explained on the basis of structural differences in the two forms which gives significant insights into the action of sucralfate in relation to its structure.

Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination.

PURPOSE: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. METHODS: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. RESULTS: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. CONCLUSIONS: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

Comparison of topical sucralfate with dexpanthenol in rat wound model.

Wound healing is a dynamic process initiated in response to injury. There are many factors that have detrimental effects on the wound healing process. Numerous studies have been conducted for improving wound healing processes. Dexpanthenol is widely used to accelerate wound healing. Sucralfate is used for the treatment of peptic ulcers. We aimed to compare the efficacy of topical Dexpanthenol and Sucralfate in an experimental wound model in rats via histopathological examinations and immune histochemical determinations, as well, to evaluate their effects on EGF levels. Three different groups were formed: the Control Group, the Dexpanthenol Group and the Sucralfate Group. Full-thickness skin wounds were created on the back of each rat and isotonic saline was applied to the wounds of the rats in the control group, Bepanthol® cream was applied in Dexpanthenol Group and 10% Sucralfate cream was applied in Sucralfate Group, once a day. On the 7th, 14th and 21st days the wounds were measured and seven rats from each group were sacrificed and the wounds were excised for histopathological examination. Sucralfate increased wound healing rates by increasing neovascularization, fibroblast activation, reepithelialization and collagen density, as well as dexpanthenol. Our study revealed that the dexpanthenol and sucralfate groups were better than the control group in terms of their effects on wound healing, however there was no statistically significant difference among these two groups. Sucralfate improves EGF expression in skin wounds and has positive results on skin wound healing comparable to dexpanthenol.

Design Strategy for a Hydroxide-Triggered pH-Responsive Hydrogel as a Mucoadhesive Barrier to Prevent Metabolism Disorders.

Excess nutrient uptake is one of the main factors of complications related to metabolism disorders. Therefore, efforts have emerged to modulate nutrient transport in the intestine. However, current approaches are mainly invasive interventions with various side effects. Here, a pH-responsive hydrogel is formulated by acidifying the hydroxide compounds within sucralfate to allow electrostatic interactions between pectin and aluminum ions. The pH responsiveness relies on the alternation of cations and hydroxide species, providing reversible shifting from a hydrogel to a complex coacervate system. It acts as a transient physical barrier coating to inhibit intestinal absorption and changes the viscosity and barrier function in different parts of the gastrointestinal tract, showing enhanced mucoadhesive properties. The therapeutic hydrogel remarkably lowers the immediate blood glucose response by modulating nutrient contact with bowel mucosa, suggesting potential in treating diabetes. In addition, it significantly reduces weight gain, fat accumulation, and hepatic lipid deposition in rodent models. This study provides a novel strategy for fabricating pH-responsive hydrogels, which may serve as a competent candidate for metabolism disorder management.

Effectiveness of the polyphenols-rich Sedum dendroideum infusion on gastric ulcer healing in rats: Roles of protective endogenous factors and antioxidant and anti-inflammatory mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

Acute Anisakiasis: Pharmacological Evaluation of Various Drugs in an Animal Model.

BACKGROUND: The accidental ingestion of the third larval stage of Anisakis can cause acute clinical symptoms, which are relieved via extraction of the larvae. Although this is a highly effective technique, it can only be practiced when the larvae are found in accessible areas of the gastrointestinal tract, and therefore instead the condition has often been treated using various different drugs. AIMS: This study evaluates the effectiveness of gastric acid secretion inhibitors (omeprazole and ranitidine), gastric mucosal protectants (sucralfate) and anthelmintics (mebendazole and flubendazole) in treating anisakiasis in Wistar rats. METHODS: Rats were infected with Anisakis-type I larvae and administered the drugs via a gastric probe. Data were recorded regarding the number of live and dead larvae, their location both within the animal and in its feces, and the presence of gastrointestinal lesions. Additionally, gastric pH was measured and histology performed. RESULTS: While rats in all experimental groups exhibited lesions; those treated with ranitidine and mebendazole showed significantly fewer lesions (50% and 35% of rats exhibited lesions, respectively). Histological examination of the gastric lesions revealed infection-induced changes, but no significant differences were observed between the treated and untreated rats. CONCLUSIONS: Mebendazole was found to be most efficacious in preventing gastrointestinal lesions, followed by ranitidine, which was the most effective antacid of those studied. Both these drugs could thus be considered as part of the conservative management of anisakiasis.

Efficacy of Sucralfate-Combined Quadruple Therapy on Gastric Mucosal Injury Induced by Helicobacter pylori and Its Effect on Gastrointestinal Flora.

BACKGROUND: This study explored the therapeutic efficacy of standard triple therapy combined with sucralfate suspension gel as well as the mechanisms of action in mouse models of H. pylori infection. MATERIALS AND METHODS: C57BL/6J mice were randomly divided into 5 groups: NC (natural control), HP (H. pylori infection), RAC (rabeprazole, amoxicillin, and clarithromycin), RACS (RAC and sucralfate suspension gel), and RACB (RAC and bismuth potassium citrate). HE staining and electron microscopy were performed to estimate histological and ultrastructural damages. The IL-8, IL-10, and TNF-α of gastric antrum tissues were measured by immunohistochemistry and qRT-PCR. ZO-1 and Occludin were also detected with immunohistochemistry. The genomes of gastric and fecal microbiota were sequenced. RESULTS: The eradication rate of H. pylori in the RACS group was higher than the RAC group. RACS therapy had protective effects on H. pylori-induced histological and ultrastructural damages, which were superior to the RAC group. RACS therapy reduced the protein and mRNA levels of IL-8 compared with the RAC group. The expression of Occludin in the RACS group was significantly higher than that of the RAC group. The composition of gastric and fecal microbiota for RACS was similar to the RACB group according to PCA. CONCLUSIONS: The RACS regimen eradicated H. pylori infection effectively and showed RACS had protective effects against H. pylori-induced histological and ultrastructural damage. The mechanisms of RACS effects included decreasing IL-8, enhancing Occludin, and transforming gastric microbiota. Moreover, RACS and RACB have a similar effect on gastrointestinal flora.

A Controlled Study to Examine the Effect of Topical Sucralfate on Radiofrequency-induced Burn Wounds in Rats

Several preclinical studies have shown topical sucralfate facilitates wound repair. PURPOSE: This study aimed to evaluate the effect of 10% topical sucralfate on healing radiofrequency-induced burn wounds in rats. METHODS: Twenty (20) male rats were divided into 2 equal groups. Using radiofrequency, 4 full-thickness, 1 cm in diameter round burns were created on the backs of the rats that then were randomized to receive twice-daily treatment for 30 days with 10% sucralfate or neutral cream. Biopsies were taken on days 4, 7, 14, and 21 to analyze fibrin-leukocyte crut, edema density, epidermal-dermal cell infiltration, amount of fibroblast and collagen fibers, amount of elastic fibers, neovascularization-angiogenesis, and reepithelialization-granulation tissue. Data were collected to a spreadsheet and entered into statistical software for analysis. Histopathological features were classified as categorical variables and compared using the χ2 test and Fisher's exact test. When χ2 was used, Yates' correction for continuity was performed. All reported P values were 2-tailed; P less than .05 was considered statistically significant. RESULTS: On day 4, improvement in edema density (P = .034), epidermal detachment (P = .020), epidermal-dermal cell infiltration (P = .007), and polymorphonuclear leukocyte infiltration (P = .021) were statistically more significant in the sucralfate than control group. On day 7, epidermal-dermal cell infiltration (P = .007) and elastic fibers P = .050) were statistically more significant in the sucralfate group. On day 14, angiogenesis (P = .029), reepithelialization (P = .035), and granulation tissue (P = .003) were statistically more significant in the sucralfate group. By the end of the study (day 30), angiogenesis (P = .010), reepithelialization (P <.001), fibroblast density (P = .016), granulation tissue (P = .035), and collagen density (P = .002) were significantly improved in the sucralfate group versus the control group. CONCLUSION: In a rat wound model, 10% topical sucralfate was found to histopathologically facilitate the healing process compared to the control group. Controlled clinical studies are needed to elucidate the effect of this treatment in human wounds.

Oral Viscous Sucralfate Gel for Post-procedural Treatment of Barrett's Esophagus.

Barrett's esophagus refers to an abnormal change in the cells of the lower portion of the esophagus. It is characterized by the replacement of the normal stratified squamous epithelium lining of the esophagus by columnar epithelium cells which are usually found lower in the gastrointestinal tract. The medical significance of this pathology is approximately 0.5% risk to develop esophageal adenocarcinoma (per patient diagnosed with Barrett's esophagus per year). Diagnosis requires endoscopy and biopsy. In general, high-grade dysplasia and early stages of adenocarcinoma can be treated by endoscopic resection and/or endoscopic ablative therapy, whereas advanced stages (submucosal) are generally advised to undergo surgical treatment. Patients who undergo endoscopic resection and/or endoscopic ablative therapy might suffer from retrosternal discomfort and transient dysphagia, adverse effects that sometimes accompanies these procedures. One of the common post-procedural treatments is sucralfate 1 g 3 to 4 times daily for two weeks after the procedure. The rational for this treatment is to enhance the wound-healing process in the esophagus tissues and to coat the wounded tissues with a cytoprotective agent. As no clinical trials have been performed in order to prove the efficacy of sucralfate in the postprocedural treatment of Barrett's esophagus, this article summarizes the clinical experience accumulated from the treatment with sucralfate as a wound-healing enhancer. In addition, the article deals with the hypothesized mechanism of action of sucralfate and gives one option for compounding sucralfate oral viscous gel.

Effectiveness of Topical Sucralfate in the Management of Pressure Ulcer in Hospitalized Patients: A Prospective, Randomized, Placebo-Controlled Trial.

BACKGROUND: The aim of this study was to evaluate the effectiveness of topical sucralfate in the management of pressure ulcer (PU) in hospitalized patients. METHODS: Forty hospitalized patients with stage II PU were included in this prospective, double-blind, randomized, placebo-controlled trial and were randomly divided into 2 groups receiving either sucralfate gel or placebo, on a daily basis. The patients were visited every day for 14 days, the ulcer was evaluated using the Pressure Ulcer Scale for Healing (PUSH) and changes to the measured scores over time were used as an indicator of wound healing. RESULTS: There were no statistically significant differences in any of the demographic characteristics between both groups. Both of the interventions reduced the average PUSH score, and at the end of the trial, all but 2 patients were healed. One in each group discontinued the trial because of exacerbation of the ulcer. No significant between-group difference in the average PUSH score reduction was observed (6.36 ± 2.11 vs. 5.89 ± 1.41, P = 0.42). Although the average healing time was less in the sucralfate group (6.05 ± 2.17 vs. 7.78 ± 3.42), the difference was not statistically significant (P = 0.07). CONCLUSIONS: Sucralfate gel does not improve healing of PU compared with placebo.

Effect of sucralfate against hydrochloric acid-induced dental erosion.

OBJECTIVE: Devising effective measures for the prevention of hydrochloric acid (HCl)-induced erosion is of great significance. This is even more important in dentine, in which products have limited diffusion. Therefore, agents that can bind to proteins forming an acid-resistant gel-like coat, such as sucralfate, may stand out as a promising alternative. This study investigated the protective effect of sucralfate suspensions against HCl-induced dental erosion. MATERIALS AND METHODS: In the first experiment, hydroxyapatite (HAp) crystals were pre-treated with a commercial sucralfate suspension (CoSS, pH 5.9), a stannous-containing sodium fluoride solution (NaF/SnCl2 pH 4.5), two prepared sucralfate suspensions (PrSS, pH 5.9 and 4.5), or deionized water (DI, control). HAp dissolution was measured using a pH-stat system. In a subsequent experiment, embedded/polished enamel and root dentine slabs were allocated into five groups to be treated with one of the tested substances prior to and during erosion-remineralization cycles (HCl-2 min + artificial saliva 60 min, two times per day, 5 days). Surface loss was assessed profilometrically. Data were analyzed by ANOVA and Tukey's tests. RESULTS: HAp dissolution was as follows: NaF/SnCl2 < CoSS < PrSS/pH 4.5, while PrSS/pH 5.9 = DI and both did not differ from CoSS and PrSS/pH 4.5. In enamel, surface loss did not differ between CoSS and PrSS/pH 4.5, with both having lower surface loss than PrSS/pH 5.9 and DI and NaF/SnCl2 differing only from DI. In root dentine, surface loss was as follows: CoSS < PrSS/pH 5.9 < (NaF/SnCl2 = DI), while PrSS/pH 4.5 = CoSS = PrSS/pH 5.9. CONCLUSION: Sucralfate suspension provided anti-erosive protection to HCl-induced erosion. CLINICAL RELEVANCE: Sucralfate may protect teeth against erosion caused by gastric acid.

A pilot study investigating the in vitro efficacy of sucralfate against common veterinary cutaneous pathogens.

OBJECTIVE: To determine whether Cicalfate® (Avene), a commercially available skin cream, or its active ingredient - sucralfate - demonstrate in vitro antimicrobial effect against common veterinary cutaneous pathogens. MATERIALS AND METHODS: Prospective study assessing in vitro susceptibility of standardised and clinical strains of common veterinary cutaneous pathogens to titrated concentrations of sucralfate in either saline solution (range 0∙2 to 200 mg/mL) or in Cicalfate® restorative cream solubilised in DMSO (range 0∙002 to 1 mg/mL). Minimum inhibitory concentrations were determined by broth dilution in accordance with Clinical and Laboratory Standards Institute guidelines. RESULTS: Both solutions demonstrated in vitro inhibitory effects against strains of Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus pseudintermedius, Escherichia coli and Enterococcus faecalis. Minimum inhibitory concentration ranges for susceptible bacteria tested in Cicalfate® solution and sucralfate solution were 0∙06 to 0∙25 mg/mL and 25 to 50 mg/mL, respectively. Sucralfate solution did not demonstrate antimicrobial effects against laboratory strains of S. aureus and E. faecalis and neither solution demonstrated antimicrobial effects against the clinical strain of P. aeruginosa. For organisms inhibited by sucralfate, Cicalfate® solution inhibited growth at lower sucralfate concentrations than sucralfate solution. CLINICAL SIGNIFICANCE: The results of this pilot study suggest that Cicalfate® and sucralfate demonstrate in vitro antibacterial activity. Further in vitro and clinical studies are warranted to confirm these observations and determine their clinical utility in the treatment of superficial pyoderma.

Effect of sucralfate on gastric permeability in an ex vivo model of stress-related mucosal disease in dogs.

BACKGROUND: Sucralfate is a gastroprotectant with no known systemic effects. The efficacy of sucralfate for prevention and treatment of stress-related mucosal diseases (SRMD) in dogs is unknown. HYPOTHESIS/OBJECTIVES: To develop a canine ex vivo model of SRMD and to determine the effect of sucralfate on mucosal barrier function in this model. ANIMALS: Gastric antral mucosa was collected immediately postmortem from 29 random-source apparently healthy dogs euthanized at a local animal control facility. METHODS: Randomized experimental trial. Sucralfate (100 mg/mL) was applied to ex vivo canine gastric mucosa concurrent with and after acid injury. Barrier function was assessed by measurement of transepithelial electrical resistance (TER) and radiolabeled mannitol flux. RESULTS: Application of acidified Ringers solution to the mucosal side of gastric antrum caused a reduction in gastric barrier function, and washout of acidified Ringers solution allowed recovery of barrier function (TER: 34.0 ± 2.8% of control at maximum injury, 71.3 ± 5.5% at recovery, P < .001). Sucralfate application at the time of injury or after injury significantly hastened recovery of barrier function (TER: 118.0 ± 15.2% of control at maximum injury, P < .001 and 111.0 ± 15.5% at recovery, P = .35). CONCLUSIONS AND CLINICAL IMPORTANCE: Sucralfate appeared effective at restoring defects in gastric barrier function induced by acid and accelerating repair of tissues subjected to acid in this model, suggesting that sucralfate could have utility for the treatment and prevention of SRMD in dogs.

Complementarity of in vitro and in vivo models for the evaluation of gastro-protective effects of pharmacological substances.

Gastric mucosa is frequently exposed to various gastric irritants, and there is a continuing requirement to develop new gastro-protective agents. This study compares the effects of three such agents, sucralfate, rebamipide, and cimetidine in both in vivo and in vitro indomethacin-induced gastric damage models. For the in vivo approach, rats were orally administered sucralfate, rebamipide, and cimetidine at 300 mg/kg before an acute dose of indomethacin (30 mg/kg). Gastric lesions were then macroscopically examined. For the in vitro approach, gastric mucosal cells were incubated with sucralfate (3 and 5 mg/mL), rebamipide (0.3 and 1 mm), and cimetidine (10 and 50 µg/mL) before exposure to indomethacin (3.8 mm). The release of lactate dehydrogenase (LDH) and mitochondrial function were then measured. Sucralfate, rebamipide, and cimetidine displayed gastro-protective effects in vivo (decreased number of gastric ulcers: -50% P < 0.05, -22% NS, and -69% P < 0.05, respectively, and reduced length of gastric lesions: -62% P < 0.05, -29% NS, and -70% P < 0.001, respectively). Cell damage induced by indomethacin in vitro was inhibited by sucralfate (LDH release) and by rebamipide and cimetidine (mitochondrial function and LDH release). In contrast, sucralfate accentuated the indomethacin-induced decrease in mitochondrial function. Although cultured gastric cells offer a promising tool for evaluating the cytotoxic or protective effects of test compounds, data from in vivo models are still needed to confirm in vitro data. Using both approaches provides more comprehensive insight into the effects of test compounds on the gastric mucosa.

A distinct microbiota composition is associated with protection from food allergy in an oral mouse immunization model.

In our mouse model, gastric acid-suppression is associated with antigen-specific IgE and anaphylaxis development. We repeatedly observed non-responder animals protected from food allergy. Here, we aimed to analyse reasons for this protection. Ten out of 64 mice, subjected to oral ovalbumin (OVA) immunizations under gastric acid-suppression, were non-responders without OVA-specific IgE or IgG1 elevation, indicating protection from allergy. In these non-responders, allergen challenges confirmed reduced antigen uptake and lack of anaphylactic symptoms, while in allergic mice high levels of mouse mast-cell protease-1 and a body temperature reduction, indicative for anaphylaxis, were determined. Upon OVA stimulation, significantly lower IL-4, IL-5, IL-10 and IL-13 levels were detected in non-responders, while IL-22 was significantly higher. Comparison of fecal microbiota revealed differences of bacterial communities on single bacterial Operational-Taxonomic-Unit level between the groups, indicating protection from food allergy being associated with a distinct microbiota composition in a non-responding phenotype in this mouse model.

Bariatric Embolization: Pilot Study on the Impact of Gastroprotective Agents and Arterial Distribution on Ulceration Risk and Efficacy in a Porcine Model.

PURPOSE: To assess whether the number of fundal arteries embolized and use of gastroprotective agents have an impact on ghrelin suppression and gastric ulceration rates. MATERIALS AND METHODS: Twenty-two healthy, growing swine (mean, 38.4 kg; range, 30.3-47.0 kg) were evaluated. Six control swine underwent a sham procedure. Gastric embolization was performed by the infusion of 40-µm microspheres selectively into some or all gastric arteries supplying the gastric fundus. In group 1, 6 swine underwent embolization of all 4 arteries to the gastric fundus. In group 2, 5 swine underwent embolization of 2 gastric fundal arteries. In group 3, 5 swine underwent embolization of 1 gastric fundal artery. Animals in groups 2 and 3 were treated with gastroprotective agents (sucralfate and omeprazole). Weight and fasting plasma ghrelin levels were analyzed at baseline and at week 4. Upon animal euthanasia, gross analysis was performed for identification of ulcers. RESULTS: Only group 1 animals exhibited changes in serum ghrelin levels that rendered them significantly lower than those in control animals (P = .049). Group 3 animals exhibited marked elevations in serum ghrelin levels compared with control animals (P = .001). Gross pathologic evaluation revealed 0 ulcers in the control animals, 3 ulcers (50%) in group 1, 2 ulcers (40%) in group 2, and 2 ulcers (40%) in group 3. CONCLUSIONS: Administration of gastroprotective agents and embolization of fewer arteries to the gastric fundus did not prevent gastric ulceration in treated animals. Only animals that underwent embolization of all gastric arteries exhibited significant decreases in serum ghrelin levels.

Novel self-assembled mesalamine-sucralfate complexes: preparation, characterization, and formulation aspects.

Two well-known active agents, mesalamine (MES) and sucralfate (SUC), were investigated for possible utilization as fixed-dose combination product. The anti-inflammatory action of MES in association with bioadhesiveness and mucosal healing properties of SUC were considered promising for the development of a new compound containing both molecules, aimed as an improved treatment of ulcerative colitis. The present study investigates the capacity of the two active agents to interact and generate a new and stable entity via self-assembling. Spray-drying was used to co-process the two active principles from an aqueous mixture where the ratio MES:SUC was in the range 25:75, 50:50, and 75:25. The structural data (X-Ray, FTIR, SEM, DSC, and (1)H NMR) have shown that MES and SUC are interacting leading to complexes with properties differing from those of each separate active agent and from their physical blends. (1)H NMR results indicated that complexation occurred when the aqueous suspensions of drugs were mixed, prior to spray-drying. Drug-drug self-assembling was the driving mechanism in the formation of the new entity. Based on the structural data, a hypothetical structure of the complex was proposed. Co-processing of MES and SUC represents a simple and useful procedure to prepare new self-assembled compounds by valorizing the ionic interactions between the two entities. Preliminary studies with oral solid dosage forms based on MES-SUC complexes tested in vitro have shown a controlled MES release, opening the perspective of a new colon-targeted delivery system and a novel class of compounds with therapeutic application in inflammatory bowel diseases.

Medicina antienvelhecimento: notas sobre uma controvérsia sociotécnica / Anti-aging medicine: notes on a socio-technical controversy

Após algumas décadas de batalha, a geriatria e a gerontologia se tornaram as legítimas ciências do envelhecimento. Hoje surge uma contestação a tal condição. Em sua breve história, a medicina antienvelhecimento se afirmou como prática médica que questiona o modo de se endereçar o envelhecimento biológico. Com isso, toda a medicina é questionada. Aqui, exploramos especialmente como essa controvérsia se estrutura em torno dos fundamentos das ciências do envelhecimento. Há bases para esses questionamentos? Como eles foram tratados por aqueles que os receberam? Tendo em vista uma perspectiva sociotécnica, é interessante pensar que, para geriatras e gerontólogos, a necessária crítica à medicina antienvelhecimento também traz uma importante reflexão sobre o modo como as ciências do envelhecimento vêm tratando seu objeto.

After some decades of struggle, geriatrics and gerontology have become the legitimate sciences of aging. Today, their status is being questioned. In its short history, anti-aging medicine has taken root as a medical practice that questions how to address biological aging. In so doing, all medicine is questioned. Here, we explore in particular how this controversy is structured around the founding principles of the sciences of aging. Is there any basis for these questionings? How have they been treated by those who have received them? Taking a socio-technical viewpoint, it is worth considering that for geriatricians and gerontologists, the need to criticize anti-aging medicine also raises some important reflections about how the sciences of aging address their subject.

Evaluation of the application of enemas containing sucralfate in tissue content of neutral and acid mucins in experimental model of diversion colitis.

PURPOSE: To evaluate the effects of sucralfate on tissue content of neutral and acids mucins in rats with diversion colitis. METHODS: Thirty-six rats were submitted to a proximal right colostomy and a distal mucous fistula. They were divided into two groups according to sacrifice to be performed two or four weeks after intervention. Each group was divided into three subgroups according daily application of enemas containing saline, sucralfate at 1.0 g/kg/day or 2.0 g/kg/day. Colitis was diagnosed by histological analysis and neutral and acid mucins by Periodic Acid Schiff and Alcian Blue techniques, respectively. The contents of mucins were quantified by computer-assisted image analysis. Student's t paired and ANOVA test were used to compare the contents of both types of mucins among groups, and to verify the variance with time, establishing level of signification of 5% for both (p<0.05). RESULTS: Enemas containing sucralfate improves the inflammation and increases the tissue contents of neutral and acid mucins. The content of neutral mucins does not change with the time or concentration of sucralfate used, while acid mucins increases with concentration and time of intervention. CONCLUSIONS: Sucralfate enemas improve the inflammatory process and increase the tissue content of neutral and acid mucins in colon without fecal stream.

Evaluation of the application of enemas containing sucralfate in tissue content of neutral and acid mucins in experimental model of diversion colitis

PURPOSE: To evaluate the effects of sucralfate on tissue content of neutral and acids mucins in rats with diversion colitis. METHODS: Thirty-six rats were submitted to a proximal right colostomy and a distal mucous fistula. They were divided into two groups according to sacrifice to be performed two or four weeks after intervention. Each group was divided into three subgroups according daily application of enemas containing saline, sucralfate at 1.0 g/kg/day or 2.0 g/kg/day. Colitis was diagnosed by histological analysis and neutral and acid mucins by Periodic Acid Schiff and Alcian Blue techniques, respectively. The contents of mucins were quantified by computer-assisted image analysis. Student's t paired and ANOVA test were used to compare the contents of both types of mucins among groups, and to verify the variance with time, establishing level of signification of 5% for both (p<0.05). RESULTS: Enemas containing sucralfate improves the inflammation and increases the tissue contents of neutral and acid mucins. The content of neutral mucins does not change with the time or concentration of sucralfate used, while acid mucins increases with concentration and time of intervention. CONCLUSIONS: Sucralfate enemas improve the inflammatory process and increase the tissue content of neutral and acid mucins in colon without fecal stream. .