Gastrointestinal Spasm Research Articles

Evaluation of the mechanism of action of paracetamol, drotaverine, and peppermint oil and their effects in combination with hyoscine butylbromide on colonic motility: human ex-vivo study.

Drotaverine, paracetamol, and peppermint oil are often prescribed for the treatment of gastrointestinal spasm and pain. This study aimed to evaluate the effect of these drugs alone and combined with the well-known antispasmodic hyoscine butylbromide on the human colon. Colon samples were obtained from macroscopically normal regions of 68 patients undergoing surgery and studied in muscle bath. Drotaverine, paracetamol, and peppermint oil were tested alone and in combination with hyoscine butylbromide on (1) spontaneous contractility induced by isometric stretch (in the presence of 1µM tetrodotoxin) and (2) contractility induced by 10-5M carbachol and after (3) electrical field stimulation-induced selective stimulation of excitatory (in the presence of 1mMNω-nitro-L-arginine and 10µM MRS2179) and (4) inhibitory (under non-adrenergic, non-cholinergic conditions) pathways. (5) Drotaverine alone was also tested on cAMP-dependent pathway activated by forskolin. Compared with the vehicle, drotaverine and paracetamol (10-9-10-5M) did not modify spontaneous contractions, carbachol-induced contractions, and responses attributed to selective activation of excitatory pathways. The addition of hyoscine butylbromide (10-7-10-5M), concentration-dependently reduced myogenic contractions and carbachol- and electrical field stimulation-induced contractile responses. The association of paracetamol (10-4M) and hyoscine butylbromide (10-7-10-5M) was not different from hyoscine butylbromide alone (10-7-10-5M). At higher concentrations (10-3M-3*10-3M), paracetamol decreased myogenic and carbachol-induced contractions. The adenylate cyclase activator, forskolin, concentration-dependently reduced contractility, leading to smooth muscle relaxation. The effect of forskolin 10-7M was concentration-dependently enhanced by drotaverine (10-6M-10-5M). Peppermint oil reduced myogenic activity and carbachol- and electrical field stimulation-induced contractions. The association of hyoscine butylbromide and peppermint oil was synergistic since the interaction index measured with the isobologram was lower than 1. No effect was seen on the neural-mediated inhibitory responses with any of the drugs studied although peppermint oil reduced the subsequent off-contraction. Drotaverine and hyoscine butylbromide have a complementary effect on human colon motility as one stimulates the cAMP inhibitory pathway and the other inhibits the excitatory pathway. Peppermint oil is synergic with hyoscine butylbromide suggesting that a combination therapy may be more effective in treating patients. In contrast, at therapeutic concentrations, paracetamol does not modify colonic contractility, suggesting that the association of paracetamol and hyoscine butylbromide has independent analgesic and antispasmodic properties.

Pharmacological disadvantages in the spasmolytic effects by using the mixture known as “three toronjiles” in folk medicine

Ethnopharmacology relevanceIn Mexico, Agastache mexicana subsp. mexicana (PT) and subsp. xolocotziana (WT), and Dracocephalum moldavica (BT), are used together as the “three toronjiles” to treat gastrointestinal spasms. Aim of studyTo evaluate if the spasmolytic activity of these three medicinal species is better in combination or in an individual manner. Materials and methodsSpasmolytic effect of PT, WT and BT alone or combinate were evaluated in rings of the guinea-pig ileum contracted with potassium chloride (KCl), electrical field stimulation (EFS), or acetylcholine (ACh). Chemical analysis by thin layer and ultra-high pressure liquid chromatography of the aqueous extracts of each species were done for their comparison, and their acute toxicity were determined in mice. ResultsPT and WT diminished in a dose-dependent manner the contractions induced by KCl, EFS, and ACh. Whereas BT did not altered contractions in any experimental protocol. A combination of the PT (EC50) and WT (EC50) diminished the contractions induced by KCl or EFS. Interestingly, the addition of BT extract (10 μg/ml) to the combination (PT EC30 + WT EC30) blocked the inhibitory effect produced on the contracted tissue in the presence of KCl, EFS, or ACh. Moreover, addition of BT extract (100 μg/ml) to the same combination blocked the inhibitory effect on the pre-contracted tissue only in the presence of EFS. None of the aqueous extracts produced toxicity in its individual administration in mice. Chemical analysis demonstrated similarities between PT and WT, but differences with BT. ConclusionsThe results of this study confirmed that either combined or by themselves aqueous extracts of PT and WT produced a spasmolytic action on guinea pig ileum, suggesting that this combination of medicinal plants could relieve gastrointestinal diseases in human, but when BT aqueous extract is added to those obtained with PT and WT, the spasmolytic activity diminished or even was blocked. Our results give evidence that mixture of several plants might produce disadvantages in the medicinal properties of their individual activity.

Antibacterial, Antibiofilm and Anti-Inflammatory Activities of Eugenol Clove Essential Oil against Resistant Helicobacter pylori.

Eugenol essential oil (EEO) is the major component in aromatic extracts of Syzygium aromaticum (clove) and has several biological properties, such as antibacterial, antioxidant, and anti-inflammatory activities, as well as controlling vomiting, coughing, nausea, flatulence, diarrhea, dyspepsia, stomach distension, and gastrointestinal spasm pain. It also stimulates the nerves. Therefore, the aim of this study was to extract and purify EEO from clove buds and assess its ability to combat resistant Helicobacter pylori. Additionally, EEO's anti-inflammatory activity and its ability to suppress H. pylori biofilm formation, which is responsible for antibiotic resistance, was also investigated. Syzygium aromaticum buds were purchased from a local market, ground, and the EEO was extracted by using hydro-distillation and then purified and chemically characterized using gas chromatography-mass spectrometry (GC-MS). A disk-diffusion assay showed that Helicobacter pylori is sensitive to EEO, with an inhibition zone ranging from 10 ± 06 to 22 ± 04 mm. The minimum inhibition concentration (MIC) of EEO ranged from 23.0 to 51.0 μg/mL against both Helicobacter pylori clinical isolates and standard strains. In addition, EEO showed antibiofilm activity at 25 µg/mL and 50 µg/mL against various Helicobacter pylori strains, with suppression percentages of 49.32% and 73.21%, respectively. The results obtained from the anti-inflammatory assay revealed that EEO possesses strong anti-inflammatory activity, with human erythrocyte hemolysis inhibition percentages of 53.04, 58.74, 61.07, and 63.64% at concentrations of 4, 8, 16, and 32 μg/L, respectively. GC-MS analysis revealed that EEO is a major component of Syzygium aromaticum when extracted with a hydro-distillation technique, which was confirmed by its purification using a chemical separation process. EEO exhibited antibacterial action against resistant Helicobacter pylori strains, as well as antibiofilm and anti-inflammatory activities, and is a promising natural alternative in clinical therapy.

Potential biomedical applications of Araucaria araucana as an antispasmodic, bronchodilator, vasodilator, and antiemetic: Involvement of calcium channels

Ethnopharmacological relevanceSince pre-Columbian era, the resin of Araucaria araucana tree has been used traditionally for the treatment of ulcers and wounds. Araucaria species have also been used to treat inflammation, respiratory problems, viral infections, ulcers, and rheumatoid, cardiovascular, and neurological disorders. Aims and objectiveDue to its popular use, the authors aimed to scrutinize the potential of this plant as an antispasmodic and an antiemetic agent. Furthermore broncho- and vasodilatory effects of this plant was explored to rationalize its folkloric uses. Materials and methodsAraucaria araucana crude extract (Aa.Cr) was evaluated in isolated preparations of rabbit jejunum, trachea, aorta, and atria to investigate the antispasmodic, bronchodilator, and vasodilator effects. The potential mechanistic approaches were compared with the standard drug ‘verapamil’. The antiemetic activity was determined and compared with the standard drug ‘domperidone’ via chick emesis model. ResultsAa.Cr dose-dependently relaxed both spontaneous and K+-induced contractions in the isolated jejunum preparations of rabbits. In concentration–response curves of calcium (Ca++), Aa.Cr also triggered the rightward shift like verapamil. Applying carbachol and phenylephrine (1 μM) and K+ (80 mM) to the isolated tracheal and aortic tissue preparation, respectively, resulted in broncho- and vasodilatory activities, respectively which may be due to the inhibition of Ca++ channels. Aa.Cr inhibited atrial force and spontaneous contractions in the rabbit's right atria. Aa.Cr exhibited significant antiemetic activity (P < 0.001 vs. saline) in dose-dependent (50–150 mg/kg) manner like domperidone. In silico molecular docking was performed to investigate the biological targets of purified components of Aa.Cr which revealed that cadinol dominantly targets β2 receptors to cause bronchodilation, however, eudesmin binds non-specifically to all the selected targets, while secoisolariciresinol mediated high hydrogen bonding with muscarinic receptors (M1 and M3) and Ca++ channels, thus shows the suggested mechanistic pathways of targeted activities. ConclusionsThe results of this study indicates that Aa.Cr may exhibit antispasmodic activity, bronchodilation, and vasodilation by inhibiting voltage-dependent Ca++ channels and release of subcellular calcium. This explains its folkloric use in hypertension, bronchospasms, gastrointestinal spasms, and emesis.

Drug Interaction of Hypericum Perforatum with Routine Chemical Drugs

In traditional medicine, Hypericum perforatum L. is used as an antidepressant, diuretic, analgesic, antisepticand wound healing, anticonvulsant, rheumatism and chronic gastrointestinal spasms, abortion, sciatica, andfor the treatment of infectious diseases such as syphilis, tuberculosis, dysentery, pertussis, worm excretion,and malaria. H. perforatum interferes with cardiac drugs, anesthetics, narcotics and analgesics, antibiotics,hormonal compounds, antiviral compounds, anticonvulsants and antidepressants, organ transplantationcompounds, and iron compounds. Despite the medicinal effects of the valuable plant H. perforatum, thesingle use of this plant is very effective and valuable in the treatment of diseases and disorders, but its usewith other chemical drugs due to the occurrence of drug interactions requires caution in consumption.

A Review Focused on Molecular Mechanisms of Anxiolytic Effect of Valerina officinalis L. in Connection with Its Phytochemistry through in vitro/in vivo Studies.

Valeriana officinalis L. (Valerianaceae) is one of the most reputed ancient medicinal plants used in modern phytotherapy and traditional medicine. Its root extract is one of the most effective herbal sedatives and tranquilizers, where the plant is also used for the treatment of gastrointestinal spasms. V. officinalis has complex phytochemistry consisting of the esterified iridoid derivatives known as valepotriates (e.g., valtrate, didrovaltrate, isovalerenic acid), sesquiterpenes (e.g., valerenic acid), flavonoids (e.g., linarin, apigenin), lignans (e.g., pinoresinol, hydroxypinoresinol), alkaloids (e.g., actinidine, valerine), triterpenes (e.g., ursolic acid), monoterpenes (e.g., borneol, bornyl acetate). Among them, valerenic acid is a marker compound for standardization of the root extracts of the plant and has been reported in many in vitro/in vivo studies to be responsible for anxiolytic action of the plant. Although modulation of gamma-aminobutyric acid (GABA) receptors has been revealed to be the leading mechanism of the plant-based on the existence of valerenic acid, several studies described the interaction of valerenic acid with glutamergic receptors. In addition to valerenic acid, isovaleric acid, didrovaltrate, borneol, and some lignans have also been proposed to contribute to the anxiolytic effect of the plant. In the current review, the data selectively scrutinized from the in vitro/in vivo studies about identifying anxiolytic molecular mechanisms of V. officinalis is focused.

Advanced Strategies for Production of Natural Products in Yeast.

Natural products account for more than 50% of all small-molecule pharmaceutical agents currently in clinical use. However, low availability often becomes problematic when a bioactive natural product is promising to become a pharmaceutical or leading compound. Advances in synthetic biology and metabolic engineering provide a feasible solution for sustainable supply of these compounds. In this review, we have summarized current progress in engineering yeast cell factories for production of natural products, including terpenoids, alkaloids, and phenylpropanoids. We then discuss advanced strategies in metabolic engineering at three different dimensions, including point, line, and plane (corresponding to the individual enzymes and cofactors, metabolic pathways, and the global cellular network). In particular, we comprehensively discuss how to engineer cofactor biosynthesis for enhancing the biosynthesis efficiency, other than the enzyme activity. Finally, current challenges and perspective are also discussed for future engineering direction.

Effectiveness of mebeverine in patients with post-cholecystectomy gastrointestinal spasm: results of prospective observational program "odyssey".

To assess the effectiveness of mebeverine 200 mg BID in patients with post-cholecystectomy gastrointestinal spasm not requiring surgical treatment. 218 patients were included in 16 clinical centers in 14 cities in Russia. All patients had post-cholecystectomy gastrointestinal spasms, not requiring surgical treatment and received mebeverine (Duspatalin®) 200 mg BID. The observational assessment period lasted from the moment of their inclusion into the study up to 6 weeks post inlusion. The therapy results were evaluated using visual analog scales (GPA and 11-point numeric rating scale) by patient self-assessment of the dynamics of spasm/discomfort and other post-cholecystectomic gastrointestinal symptoms after 2 and 6 weeks of treatment. Gastrointestinal Quality of Life Index (GIQLI) was used to assess patient quality of life. All 218 patients completed the 2-week mebeverine treatment course, 101 of them finished the 6-week course ("prolonged population"). Significant positive changes in the relief of abdominal pain and dyspepsia were noted as well as normalization of stool frequency and consistency. A more marked change in values was observed during prolonged (up to 6 weeks) therapy. Both 2-week and 6-week mebeverine courses led to a normalization of patient quality of life. After 6 week therapy, an effect of mebeverine on the quality of life 91% of patients was observed comparable to cholecystectomy itself, speficially related to the quality of life subscore 'symptoms'. The results of our study demonstrate that mebeverine (Duspatalin®) therapy leads to an effective elimination of clinical symptoms associated with post-cholecystectomy GI-spasm disorders, like abdominal pain, symptoms of dyspepsia and stooldisorders. A more marked change in values was observed during prolonged (up to 6 weeks) therapy.

Relaxant effects of Azadirachta indica A. Juss var. siamensis Valeton flower extract on isolated rat ileum contractions and the mechanisms of action

Azadirachta indica A. Juss var. siamensis Valeton or commonly known as Siamese neem is one of the most well-known plant in traditional Ayurvedic medicine. The aim of the present study was to investigate the relaxant effects of A. indica on isolated rat ileum contractions and its potential underlying mechanisms involved. The isometric contractions of ileum segments were investigated in organ baths for spontaneous activity and response to aqueous extract of Siamese neem flower (SNF). The spasmolytic action of the extract was also assessed on contraction induced by acetylcholine and high potassium. Our findings indicate that cumulative concentrations of SNF aqueous extract induced relaxant effect on spontaneous rat ileum contractions. The extract has also suppressed the cumulative concentration response curve for acetylcholine and pottasium ions-induced contraction. The presence and absence of propranol (antagonist of β-adrenergic receptor) and l-Name (antagonist of nitric oxide synthase) in SNF aqeous extract co-treatment demonstrated no significant different in term of contraction activity when compared to SNF extract treatment alone. The treatment of SNF extract caused a significant inhibition in tissue contraction stimulated by accumulation of calcium ions. Our results showed the relaxant effect of SNF aqueous extract on the isolated rat ileum. In short, the SNF aqueous extract exhibited an inhibitory effect on the spontaneous ileum contactions particularly on the contraction stimulated by acetylcholine and high potassium. The observed effect might acted through the modulation of calcium channels. This findings provide a pharmacological basis for the traditional use of SNF for the treatment of gastrointestinal spasms.

Spasmolytic and Antimicrobial Activities of Crude Extract of Bongardia chrysogonum L. Tubers

Background and Objective: Although Bongardia chrysogonum L. (family Berberidaceae) has been used in many countries in traditional medicine to treat gastrointestinal tract disorders, scientific evidence for this treatment is lacking. The present study was carried out to assess the antimicrobial activity and to evaluate the antispasmodic potential of B. chrysogonum tuber extract. Materials and Methods: Extracts were also evaluated for antimicrobial potential against Bacillus subtilis, Staphylococcus aureus, S. epidermidis, Escherichia coli and Pseudomonas aeruginosa using the agar well diffusion method. Minimum inhibitory concentration and minimum bactericidal concentration were determined by using the micro dilution method. To evaluate the antispasmodic activity of B. chrysogonum extract on contractions induced by the spasmogens acetylcholine, BaCl2 and KCl, contractions of rat duodenum were recorded using an isolated tissue bath chamber with an isotonic transducer and oscillographic device. Results were compared by one-way analysis of variance (ANOVA) followed by Dunnett’s post test. Results: Preliminary phytochemical screening of the tuber extract revealed the presence of alkaloids, saponins, tannins and carbohydrates, including monosaccharides. No antimicrobial activity was observed against gram-positive or gram-negative bacteria; however, ethanolic B. chrysogonum tuber extract attenuated the basal contractile activity of rat duodenum smooth muscle and decreased contractions induced by acetylcholine, KCl and BaCl2, suggesting an antimuscarinic effect and/or interference of calcium influx. Alkaloids and saponins present in the extract may account for this antispasmodic effect, suggesting multiple mechanisms that can be explored in future studies. Conclusion: Taken together, results demonstrate that B. chrysogonum tuber extract possesses antispasmodic activity but not antimicrobial activity and supports its traditional use to alleviate gastrointestinal spasms.

Ethnopharmacological basis for antispasmodic, antidiarrheal and antiemetic activities of Ceratonia siliqua pods

&lt;p class="Abstract"&gt;The study was conducted to provide the ethnopharmacological bases of the crude extract of seed pods of &lt;em&gt;Ceratonia siliqua&lt;/em&gt; in the gastrointestinal spasm, diarrhea and emesis. In segregated rabbit jejunum, it showed dose-dependent (0.01-10 mg/mL) relaxation of spontaneous as well as carbachol (1 µM)-induced contraction. Pre-treatment of segregated rat ileum with &lt;em&gt;C. siliqua&lt;/em&gt;, significantly (p&amp;lt;0.0001) suppressed the carbachol (1 µM)-induced contraction similar to atropine (1 µM). These results indicated that &lt;em&gt;C. siliqua&lt;/em&gt; possesses spasmolytic activity through possible blockage of muscarinic receptor in jejunum preparations. Furthermore, the crude extract inhibited the castor oil-induced diarrhea, charcoal meal propulsion in mice and copper sulfate-induced retches in chicks in a dose-dependent manner (100, 200, 300 mg/kg). These in vitro and in vivo results indicate that &lt;em&gt;C. siliqua&lt;/em&gt; possesses the spasmolytic and antidiarrheal activities mediated possibly through blockage of muscarinic receptors. Thus, this study provides a rationale for its folkloric use.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Video Clip of Methodology&lt;/strong&gt;:&lt;/p&gt;&lt;p&gt;12 min 42 sec &lt;a href="https://www.youtube.com/v/BQGWdIZqpsY"&gt;Full Screen&lt;/a&gt; &lt;a href="https://www.youtube.com/watch?v=BQGWdIZqpsY"&gt;Alternate&lt;/a&gt;&lt;/p&gt;

Effects of Trang Phuc Linh Plus-Food Supplement on Irritable Bowel Syndrome Induced by Mustard Oil.

Trang phuc linh plus (TPLP) is a food supplement product derived from dried extracts of herbal agents Atractylodes macrocephala, Poria cocos, Paeonia lactiflora, Phellodendron amurense, and added lactobacillus fermentum lysate (ImmuneGamma®) and 5-hydroxytryptophan. TPLP is a functional food used as adjunctive treatment for treating irritable bowel syndrome (IBS). However the biological effect and its mechanism of action in IBS have not been elucidated. In this study, we aimed to determine the pharmacological activities and mode of action of TPLP on IBS animal models. Mice were given a single administration of 5% mustard oil (MO) intracollonically. Acute colitis induction by MO resulted in later development of an IBS-like accelerated upper gastrointestinal transit in mice. Mice were treated with different does of TPLP and controls. Results showed that TPLP at the dose of 654 mg/kg/day given orally significantly decreased intestinal motility (IM) compared with the control animals. The effect was similar to Duspatalin (80 mg/kg/day) (Mebeverine Hydrochloride, an antispasmodic that helps to relieve the pain and discomfort associated with gastrointestinal spasms). Increased TPLP dose (1962 mg/kg/day) had a better effect on relief of IM than Duspatalin (80 mg/kg/day). TPLP also reduced peristalsis frequency and decreased fluid volume and electrolytes excretion in intestine tested in ex vivo models. Overall, TPLP may be an effective nutraceutical supplement for IBS.

The Effect of Warm Water Intake on Bowel Movements in the Early Postoperative Stage of Patients Having Undergone Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

This study was aimed at determining the effect of oral administration of warm water during the postoperative initial stage on the time of first flatus in patients who had undergone laparoscopic cholecystectomy. In the literature, it is emphasized that warm water has favorable effects on intestinal movements such as "reliving gastrointestinal spasms and helping peristalsis return." This randomized controlled trial and experimental study was conducted in a university hospital between May and December 2011. In the study sample, we included a total of 60 patients; 30 were in the experimental group (drank warm water), while the other 30 composed the control group. Patients were randomized through a simple random sampling method. The experimental group was provided with 200 ml of warm water at 98.6°F (37°C) in the fourth postoperative hour and were made to drink it within 15 minutes. Patients received no oral intake other than warm water until the eighth postoperative hour. The oral feeding of both groups started in the eighth postoperative hour with fluids and soft food. They shifted to the normal diet as tolerated. In the analysis of the data and percentage numbers, chi-square test and Fisher's exact test, Student's t test, Mann-Whitney U test, Kruskal-Wallis variance, and correlation analysis were used. The results of the data were considered reliable and statistically significant when they were in the reliability interval of 95% and p < .05. No significant differences were found between the patients in the experimental and control groups in terms of demographic features, bowel habits, surgery durations, postoperative applications, nausea/vomiting conditions, and initial mobilization times (p > .05). Groups were homogeneously distributed. Flatus expulsion in the experimental group was 11 ± 4.2 hours and was determined to be 18.6 ± 6 hours for patients in the control group (p < .05); in contrast, no significant difference was detected in terms of the times of stool defecation (p > .05). It was determined that warm water intake in the fourth postoperative hour significantly decreased the first flatus expulsion period and had a favorable impact on intestinal movements.

Effects of dehydroeffusol on spasmogen-induced contractile responses of rat intestinal smooth muscles.

Dehydroeffusol is a naturally occurring phenanthrene isolated from Juncus effusus. In the context of screening new drugs against gastrointestinal spasms, we investigated its effects on isolated rat jejunum in vitro. Dehydroeffusol (30-90 µM) slightly and transiently enhanced contractions in a concentration-dependent manner but significantly inhibited the contractions induced by KCl (100 mM), (±)-Bay-K8644 (5 µM), pilocarpine (90 µM), and histamine (100 µM). These results show that dehydroeffusol may antagonize the spasmogenic activity of various agents, and therefore, could be a promising agent in the treatment of spasms. Its potential spasmolytic mechanism is also discussed.

SPASMOLYTIC POTENTIAL OF SOME MEDICINAL PLANTS BELONGING TO FAMILY UMBELLIFERAE: A REVIEW

Gastrointestinal s pasm is one of the most common gastrointestinal problems in infants . An herbal product i s safe and effective gastrointestinal remedy to fight against various gastrointestinal problems. Polyherbal products are in use for the treatme nt of gastrointestinal problems since ancient time. Current era has witnessed an interest in homemade remedies. A large number of modern drugs have been developed from plants. The objective of this review is to provide a consolidated report on traditional uses an d spasmolytic activities of some medicinal plants of umbelliferae family viz . Anethum graveolens , Apium graveolen se, Foeniculum vulgare , Cuminum cyminum , Pimpine l la anisum , Coriandrum sativum and Trachyspermum ammi have been extensively used for various gastrointestinal problems . Gastrointestinal spasm treatment is most common application of these plants oils. Keywo rds : Gastrointestinal p roblems , S pasm, M edicinal p lants, Umbelliferae.

Design of innovated lipid-based floating beads loaded with an antispasmodic drug: in-vitro and in-vivo evaluation

Context: Drotaverine hydrochloride (DRT) is used to treat gastrointestinal spasms accompanied with diarrhoea. Hence, the drug suffers from brief residence in the highly moving intestine during diarrhoea which leads to poor bioavailability and frequent dosing.Objective: This study aimed to extend DRT residence in the stomach.Methods: Calcium alginate floating beads were prepared using sodium alginate, isopropylmyristate (oil), and Gelucire® 43/01 (lipid) adopting emulsion gelation technique. The beads were evaluated for their floating ability, DRT entrapment efficiency and in-vitro release. Gelucire® 43/01 /oil-based beads of the selected formula were coated using ethylcellulose and different plasticizers as polyethylene glycol 400 and triethyl citrate to retard the drug release. The coated beads were re-characterized. Finally, the best formulae were investigated for their in-vivo floating ability in dogs besides their delivery to the systemic circulation compared to drug powder in human volunteers.Results: Incorporation of Gelucire® 43/01 to oil-based beads enhanced the in-vitro performance of the beads. Coated beads prepared using drug:sodium alginate ratio of 1:3 (w/w), 20% (w/v) isopropylmyristate, 20% (w/v) Gelucire® 43/01 showed promising in-vitro performance. The beads floated for 12 h in the dogs’ stomach and produced three-fold increase of the total amount of DRT absorbed within 24 h compared to that of DRT powder.Conclusions: Gelucire® 43/01 /isopropylmyristate-based calcium alginate floating beads coated with ethylcellulose using either PEG 400 or TEC as plasticizers proved to be a successful dosage form in extending DRT release.

A validated spectrofluorimetric method for the determination of nifuroxazide through coumarin formation using experimental design

BackgroundNifuroxazide (NF) is an oral nitrofuran antibiotic, having a wide range of bactericidal activity against gram positive and gram negative enteropathogenic organisms. It is formulated either in single form, as intestinal antiseptic or in combination with drotaverine (DV) for the treatment of gastroenteritis accompanied with gastrointestinal spasm. Spectrofluorimetry is a convenient and sensitive technique for pharmaceutical quality control. The new proposed spectrofluorimetric method allows its determination either in single form or in binary mixture with DV. Furthermore, experimental conditions were optimized using the new approach: Experimental design, which has many advantages over the old one, one variable at a time (OVAT approach).ResultsA novel and sensitive spectrofluorimetric method was designed and validated for the determination of NF in pharmaceutical formulation. The method was based upon the formation of a highly fluorescent coumarin compound by the reaction between NF and ethylacetoacetate (EAA) using sulfuric acid as catalyst. The fluorescence was measured at 390 nm upon excitation at 340 nm. Experimental design was used to optimize experimental conditions. Volumes of EAA and sulfuric acid, temperature and heating time were considered the critical factors to be studied in order to establish an optimum fluorescence. Each two factors were co-tried at three levels. Regression analysis revealed good correlation between fluorescence intensity and concentration over the range 20–400 ng ml-1. The suggested method was successfully applied for the determination of NF in pure and capsule forms. The procedure was validated in terms of linearity, accuracy, precision, limit of detection and limit of quantification. The selectivity of the method was investigated by analysis of NF in presence of the co-mixed drug DV where no interference was observed. The reaction pathway was suggested and the structure of the fluorescent product was proposed. Statistical comparison between the presented method and a reported spectrophotometric one was carried out on pure and pharmaceutical formulation and revealed no significant difference.ConclusionThe proposed method was considered economic, accurate, precise and highly sensitive. It could be easily applied in laboratory quality control for the analysis of NF in pure form and in pharmaceutical dosage form.

Relaxing effects of Valeriana officinalis extracts on isolated human non-pregnant uterine muscle

Abstract Objectives This study investigated the relaxing effects of Valeriana officinalis L. (Valerianaceae) on human uterine muscle. The major uses of this species in Europe are as a sedative and an anxiolytic; it is also used as a spasmolytic to treat gastrointestinal spasm. Methods We evaluated two valerian extracts (ethanolic and aqueous) in comparison with a natural mixture of valepotriates and nifedipine on spontaneous and agonist-induced contractions in non-pregnant human myometrium in vitro. Qualitative and quantitative chemical analysis was used to correlate the chemical composition of extracts with their spasmolytic effects. Myometrial strips were obtained from hysterectomy specimens of premenopausal women. Longitudinal muscle strips were mounted vertically in tissue baths under physiological conditions to record their isometric contraction. The responses of cumulative concentrations of valerian extracts on spontaneous contractions in the presence and absence of the β-adrenoceptor blocker atenolol or the cyclooxygenase inhibitor indometacin, and on agonist-induced contractions, were investigated. Key findings Valerian extracts and valepotriates inhibited uterine contra***ctility in a concentration-dependent manner. Pretreatment with either atenolol or indometacin did not affect the uterine responses to valerian extracts. Valerian extract reduced the maximal contractile response induced by acetylcholine, phenylephrine and histamine independent of the stimulus. Conclusions Valerian extracts may have direct inhibitory effects on the contractility of the human uterus and this justifies the traditional use of this plant in the treatment of uterine cramping associated with dysmenorrhoea.

Effects of Spascupreel versus hyoscine butylbromide for gastrointestinal cramps in children

Gastrointestinal spasms and cramps are common in children as well as in adults. Alternative medical practices such as chiropractice and homeopathy are becoming increasingly popular in Europe and the USA. The effectiveness and tolerability of the homeopathic preparation Spascupreel was compared with that of hyoscine butylbromide treatment in children <12 years of age. An observational cohort study in 204 children <12 years was conducted over a 1 week treatment period. The efficacy of the respective therapies were evaluated on the effect on severity of spasms and clinical symptoms (pain/cramps, sleep disturbances, distress, eating or drinking difficulties and frequent crying). Compliance was evaluated on a four-point scale from 'very good' to 'low'. Evaluation was done by the practitioner based on information given by the patient or minder. The analysis showed comparative improvements with the homeopathic preparation and hyoscine butylbromide therapy on severity of spasms, pain/cramps, sleep disturbances, eating or drinking difficulties, and frequent crying, all as evaluated by the practitioner. Both treatments were very well tolerated. For patients opting for a homeopathic therapy, Spascupreel seems to be an effective and well tolerated alternative to conventional therapies in children suffering from gastrointestinal spasms.

Hyoscine Butylbromide

Abdominal cramping and pain is a frequent problem in the adult population of Western countries, with an estimated prevalence of < or =30%. Hyoscine butylbromide (scopolamine butylbromide) [Buscopan/Buscapina] is an antispasmodic drug indicated for the treatment of abdominal pain associated with cramps induced by gastrointestinal (GI) spasms. It was first registered in Germany in 1951 and marketed in 1952, and has since become available worldwide both as a prescription drug and as an over-the-counter medicine in many countries. This article reviews the pharmacology and pharmacokinetic profile of hyoscine butylbromide, and summarises efficacy and safety data from clinical trials of this drug for abdominal cramping and pain. Pharmacological studies have revealed that hyoscine butylbromide is an anticholinergic drug with high affinity for muscarinic receptors located on the smooth-muscle cells of the GI tract. Its anticholinergic action exerts a smooth-muscle relaxing/spasmolytic effect. Blockade of the muscarinic receptors in the GI tract is the basis for its use in the treatment of abdominal pain secondary to cramping. Hyoscine butylbromide also binds to nicotinic receptors, which induces a ganglion-blocking effect. Several pharmacokinetic studies in humans have consistently demonstrated the low systemic availability of hyoscine butylbromide after oral administration, with plasma concentrations of the drug generally being below the limit of quantitation. The bioavailability of hyoscine butylbromide, estimated from renal excretion, was generally <1%. However, because of its high tissue affinity for muscarinic receptors, hyoscine butylbromide remains available at the site of action in the intestine and exerts a local spasmolytic effect.Ten placebo-controlled studies have evaluated the efficacy and safety of oral or rectal hyoscine butylbromide. Hyoscine butylbromide was considered beneficial in all of these trials, which supports its use in the treatment of abdominal pain caused by cramping. Hyoscine butylbromide is barely absorbed and detectable in the blood and does not penetrate the blood-brain barrier, and is, therefore, generally well tolerated. Few adverse events have been reported; in particular, no significant increases in the incidence of anticholinergic-related adverse effects have been observed. In summary, hyoscine butylbromide appears to be a valuable treatment option for patients with symptoms of abdominal pain or discomfort associated with cramping.