Preparation of Targeted Nanoparticles and Activity of Anti-Helicobacter Pylori

2021 ◽  
Vol 13 (8) ◽  
pp. 1458-1466
Author(s):  
Fan Zhang ◽  
Jinxia Jiang ◽  
Xiaogu He
Keyword(s):  
Helicobacter Pylori ◽  
Material Selection ◽  
Activity Index ◽  
Drug Loading ◽  
Group Testing ◽  
Disease Activity Index ◽  
Dilution Method ◽  
Aminosalicylic Acid ◽  
Targeted Nanoparticles ◽  
Il Interleukin

Helicobacter pylori (Hp) is a gram-negative spiral bacterium that grows in a microaerobic environment and can be found in people with gastritis and ulcer diseases. First, the drug 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis (UC) was investigated in this study. In order to increase the drug concentration in the diseased colon, silica nanoparticles (SNP) were prepared by the microemulsion method. Then, the drug 5-ASA was grafted onto the surface of the modified SNP, so as to obtain the targeted nanoparticles 5-ASA-SNP. The synthesis and drug loading of the materials were analyzed, and then, they were used for the treatment of colitis in the experimental mice. The inhibition of Hp ATCC700392 strain was explored according to the material selection. In the experiment, the synthesized targeted nanoparticles (5-ASA-SNP) had uniform particle size, smooth surface, and good dispersibility. Besides, the drug loading of 5-ASA reached 13.75±2.6%. In the biological toxicity analysis, the survival rate of Caco-2 cells in the 5-ASA-SNP material configuration solution reached 83.65±1.86%. In the group testing of the disease activity index (DAI) and colonic histopathology score, the H-5-ASA group and 5-ASA-SNP group were lower sharply than N-5-ASA group (P < 0.05). The expression of IL (interleukin)-6 and tumor necrosis factor (TNF)-a protein in the serum of the grouped mice from the H-5-ASA group and 5-ASA-SNP group were lower steeply than the expression of the N-5-ASA group (P < 0.05). The agar double dilution method was adopted to prepare the Hp solution according to different materials. The results confirmed that 5-ASA-SNP solution had the best antibacterial effect, and increasing the concentration of the solution can greatly inhibit the activity of Hp (P < 0.05).

scholarly journals Efficacy of 5-Aminosalicylic Acid Enemas in the Treatment of Distal Ulcerative Colitis

1990 ◽  
Vol 4 (7) ◽  
pp. 468-471 ◽  
Author(s):  
MG Robinson ◽  
DL Decktor
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
First Episode ◽  
High Dose ◽  
Aminosalicylic Acid ◽  
Open Label ◽  
Distal Ulcerative Colitis ◽  
The Mean

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.

scholarly journals P049 A new preclinical rationale for first-line therapy of ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S157-S157
Author(s):  
H Thorlacius ◽  
A Bjoerk ◽  
Ö Nordle ◽  
G Hedlund
Keyword(s):  
Ulcerative Colitis ◽  
Activity Index ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Therapeutic Effects ◽  
Aminosalicylic Acid ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Chronic Inflammatory Condition

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory condition with no known medical cure. 5-Aminosalicylic acid (5-ASA [mesalazine]) represents the cornerstone of first-line therapy for mild-to-moderate UC. Sulfasalazine (SASP) is the original agent in this class of drugs. Meta-analyses of patients with mild-to-moderately active UC comparing 5-ASA to placebo showed 5-ASA to be significantly superior to placebo. However, about two-thirds of patients treated with 5-ASA fail to enter clinical remission. It is therefore most important to identify strategies to accelerate and maximise the therapeutic effects of 5-ASA. Therapeutic intervention against NFκB activation is a useful strategy for treatment of UC. The 4-alkanoylaminobenzamide PM0503 inhibits the breakdown of the NFκB inhibitor IκBβ, and SASP/5-ASA inhibits the breakdown of IκBα. This elicited a hypothesis of a possible synergistic action and converging effect on NFκB signalling. In the present study, we investigated the effect of combining SASP/5-ASA with PM0503 in experimental colitis. Methods SASP and PM0503 alone or in combination were administered for 5 days to Balb/c mice with colitis triggered by 5% dextran sulphate sodium (DSS). Blood in the stool, stool consistency and body weight loss were evaluated daily on a 0–4 point scale. The disease activity index (DAI) was calculated by summarising the total score of these three parameters. Results Addition of 5% DSS in the drinking water for 5 days produced reproducible symptoms of colitis. PM0503 was shown to inhibit DSS induced colitis by reducing mean DAI at day 5 from 6.9 in controls to 1.7 (a 75% decrease). Mean DAI recorded with SASP treatment at optimal doses in the same series of experiments was 4.4 (a 36% decrease). Furthermore, and most important, lower doses of PM0503 acted synergistically with SASP in ameliorating DSS-induced disease severity. The combination of PM0503 and SASP using suboptimal doses having minimal beneficial effects as monotherapies, showed more than 50% disease inhibition at day 5. In addition, no toxicity was observed with PM0503 alone or in combination with SASP. Conclusion Our findings offer a preclinical rationale for simultaneous coadministration of PM0503 and a 5-ASA agent such as SASP or 5-ASA as first-line treatment for patients with UC.

Treatment of inflammatory bowel disease (IBD) in dogs and cats

2011 ◽  
Vol 14 (1) ◽  
pp. 165-171 ◽  
Author(s):  
K. Malewska ◽  
A. Rychlik ◽  
R. Nieradka ◽  
M. Kander
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Disease Activity Index ◽  
Immunosuppressive Drugs ◽  
Clinical Activity ◽  
Aminosalicylic Acid ◽  
Probiotic Treatment ◽  
Inflammatory Bowel

Treatment of inflammatory bowel disease (IBD) in dogs and catsThe treatment of inflammatory bowel disease (IBD) possesses numerous difficulties owing to the unclear etiology of the disease. This article overviews the drugs used in the treatment of IBD depending on the intensity of clinical symptoms (Canine Inflammatory Bowel Disease Activity Index and Canine Chronic Enterophaty Clinical Activity Index). Patients demonstrating mild symptoms of the disease are usually placed on an appropriate diet which may be combined with immunomodulative or probiotic treatment. In moderate progression of IBD, 5-aminosalicylic acid (mesalazine or olsalazine) derivatives may be administered. Patients showing severe symptoms of the disease are usually treated with immunosuppressive drugs, antibiotics and elimination diet. Since the immune system plays an important role in the pathogenesis of the disease, the advancements in biological therapy research will contribute to the progress in the treatment of canine and feline IBD in the coming years.

scholarly journals 5-Aminosalicylic Acid Enemas in the Maintenance of Remission in Distal Ulcerative Colitis and Proctitis

1987 ◽  
Vol 1 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Lloyd R Sutherland ◽  
Francois Martin
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Repeated Measures ◽  
Activity Index ◽  
Disease Activity Index ◽  
Distal Colon ◽  
Aminosalicylic Acid ◽  
Distal Ulcerative Colitis ◽  
Patient Groups ◽  
Maintenance Of Remission

A randomized clinical trial of the efficacy and safety of two different dosages of 5-aminosalicylic acid (5-ASA) enemas was carried out in 29 patients who had documented ulcerative colitis involving up to 50cm of distal colon. All patients were in remission or had minimal disease activity (Disease Activity Index [DAI] less than 4) at the time of study entry. The two patient groups were similar in terms of age, sex ratio and disease activity. Further significant reduction in DAI occurred during the first three months of the study. Five patients (two in the 2 g group and three in the 4g group) relapsed over the next six months. There were no significant differences in DAI of the two groups over the six month study period (ANOVA for repeated measures). Six patients dropped out of the study all of whom were in remission when last seen (mean follow-up 3. 3 months). In this preliminary study, 2 g enemas were shown to be as effective as 4 g enemas in maintaining remission in patients with ulcerative colitis confined to the distal colon.

scholarly journals Oral 5-Aminosalicyclic Acid Versus 6-Methylprednisolone in Active Crohn's Disease

1990 ◽  
Vol 4 (7) ◽  
pp. 446-451 ◽  
Author(s):  
Jürgen Schölmerich ◽  
Harro Jenss ◽  
Franz Hartmann ◽  
Hanne Döpfer ◽  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Area Under The Curve ◽  
Disease Activity Index ◽  
Entrance Examination ◽  
Aminosalicylic Acid ◽  
Double Blind ◽  
Treatment Groups ◽  
Starting Dose

The response to 5-aminosalicylic acid (5-ASA) in active Crohn's disease was studied in comparison to methylprednisolone in a 24 week randomized double-blind multicentre study. Sixty-two patients were included in the analysis. Thirty were treated with 500 mg 5-ASA qid and 32 with methylprednisolone (starting dose 48 mg for one week, then reduced weekly to 32, 24, 20, 16 and 12 mg with maintenance at 8 mg/day for the remaining 18 weeks). Mean age, earlier surgical intervention, localization of Crohn's disease and extraintestinal manifestations were not different in both groups. The Crohn's disease activity index (CDAI) and the van Hees index were not significantly different in both treatment groups at the entrance examination (median CDAI 232 in the 5-ASA group and 220 in the methylprednisolone group). According to the protocol, treatment was stopped due to insufficient efficacy in 73% of the patients receiving 5-ASA and in 34% of the patients receiving methylprednisolone (x2test P=0.0019). The area under the curve for the CDAl was significantly greater in 5-ASA (median 170) than in methylprednisolone (P≤0.007) (68). Eleven per cent of patients taking 5-ASA and 26% of patients taking methylprednisolone presented relevant side effects to treatment (not significant). It is concluded from these data that 5-ASA at the dose used in this study is not efficient in the treatment of active Crohn's disease. Considering recent studies in ulcerative colitis, a trial using a higher dose is indicated.

scholarly journals Immunotropic effect of rectal suppositories with vitamin D3 in dynamics of experimental ulcer colitis

2020 ◽  
pp. 141-145
Author(s):  
M. V. Osikov ◽  
E. V. Simonyan ◽  
M. S. Boyko ◽  
A. M. Bogomolova
Keyword(s):  
Serum Concentration ◽  
Vitamin D3 ◽  
Activity Index ◽  
Clinical Status ◽  
Disease Activity Index ◽  
Serum Concentrations ◽  
Aminosalicylic Acid ◽  
Experimental Ulcer ◽  
Specific Test ◽  
Rectal Suppositories

Purpose of the study—to develop a new dosage form—rectal suppositories with vitamin D3 and at the preclinical stage to analyze its clinical and immunological efficacy compared to 5-aminosalicylic acid (5-ASA) in the dynamics of experimental ulcerative colitis (UC) in rats.Materials and methods. UC was simulated by cutaneous and then rectal application of a 3% solution of oxazolone. Original rectal suppositories with 1500ME of vitamin D3 were administered per rectum every 12 hours, in the comparison group with the same interval, rectal suppositories with 50 mg of 5-ASA. To assess the clinical status, the Disease activity index (DAI) scale was used, the serum concentration of IgG, IgM, IL-6, IL-8 was determined by the enzyme immunoassay using rat-specific test systems on days 2 and 6 of the experiment.The results of the study. In experimental UC, DAI rises, and the concentration of IgG, IgM, IL-8 and IL-6 in serum increases on the 2nd and 6th day of the experiment. DAI increases as serum concentrations of IgG, IgM, IL-8 and IL-6 increase. The use of vitamin D3 in UC leads to a decrease in DAI and serum concentrations of IgG, IgM, IL-8, IL-6 mainly on the 6th day of observation. The use of rectal suppositories with 5-ASA in UC leads to a decrease in DAI and the concentration of IgM, IgG, IL-6, IL-8 on the 2nd and 6th day of observation.Conclusion. The efficacy of rectal suppositories containing 1500 IU of vitamin D3 in experimental UC was found to be comparable with the use of rectal suppositories with 5-ASA based on the assessment of the clinical status and serum concentration of IgM, IgG, IL-6, IL-8.

scholarly journals Efficacy and Tolerance of 5-Aminosalicylic Acid Suppositories in the Treatment of Ulcerative Proctitis: A Review of Two Double-Blind, Placebo Controlled Trials

1990 ◽  
Vol 4 (7) ◽  
pp. 472-475 ◽  
Author(s):  
CN Williams
Keyword(s):  
Placebo Group ◽  
Disease Activity ◽  
Global Assessment ◽  
Activity Index ◽  
Disease Activity Index ◽  
Aminosalicylic Acid ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Ulcerative Proctitis ◽  
Significant Difference

The efficacy and tolerance of 500 mg 5-aminosalicylic acid (mesalamine) suppositories in the treatment of ulcerative proctitis were assessed in two double-blind, placebo controlled studies of six weeks' duration, involving a total of 173 patients. In trial 1, patients used one 500 mg suppository tid. In trial 2, patients used one 500 mg suppository bid. Physician's global assessment and a disease activity index based upon patient symptoms and sigmoidoscopic appearance were used to assess efficacy. At the endpoint of trial l (tid), there was an 80.4% mean reduction in the disease activity index seen in patients treated with mesalamine compared to a 36.8% mean reduction in the placebo group (P<0.05). Analysis of the physician's global assessment indicated that 84.2% of patients receiving mesalamine were considered to be 'much improved' compared to 41 % of patients on placebo (P<0.01). At the endpoint of trial 2 (tid), there was a 74.7% mean reduction in disease activity index compared to 34.2% in the placebo group (P<0.001). Analysis of the physician's global assessment indicated that 79.2% of the mesalamine group was considered to be 'much improved' compared to 26.2% on placebo (P<0.001). There was no significant difference in efficacy seen in patients treated with 500 mg mesalamine suppositories bid or tid. Mesalamine suppositories are effective and well tolerated in the treatment of ulcerative proctitis.

scholarly journals A Double-Blind, Placebo Controlled, Multicentre Study of the Efficacy And Safety of 5-Aminosalicylic Acid Tablets in the Treatment of Ulcerative Colitis

1990 ◽  
Vol 4 (7) ◽  
pp. 463-467 ◽  
Author(s):  
LR Sutherland ◽  
M Robinson ◽  
G Onstad ◽  
M Peppercorn ◽  
N Greenberger ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Global Assessment ◽  
Activity Index ◽  
Disease Activity Index ◽  
Controlled Study ◽  
Active Ulcerative Colitis ◽  
Aminosalicylic Acid ◽  
Double Blind ◽  
Double Blind Placebo

This double-blind, placebo controlled, multicentre, parallel trial assessed the efficacy of two oral doses of a new formulation of 5-aminosalicylic acid (5-ASA) targeted to release in the cecum which was given for six weeks to 136 patients with active ulcerative colitis. Seven centres participated (two Canadian, five American). Patients were randomly assigned to one of three treatment groups (4 g 5-ASA, 2 g 5-ASA or placebo). Medication was dispensed as 250 mg identically appearing tablets containing either 5-ASA or placebo to be taken four times a day. Subjects were assessed at baseline and after three and six weeks of treatment. Assessments included a disease activity index, physician's global assessment and flexible sigmoidoscopy. Compliance was assessed through pill count. A total of 136 patients participated ( 4 7 on 4 g 5-ASA, 45 on 2 g 5-ASA, and 44 on placebo). The three groups were similar in terms of age, weight, distribution of disease, extent of disease, and previous use of steroids or sulphasalazine. Ninety patients completed the six week study. Of the 46 dropouts, 38 (82.6%) left because of insufficient efficacy ( most on either place ho or 2 g 5-ASA), four (8.7%) had adverse reactions (all on 5-ASA), the remaining four (8.7%) left for reasons not related to their ulcerative colitis. The disease activity index represents a composite score ( maximum of 12) with categories for number of daily stools, presence of bleeding, abdominal pain and physician's assessment of disease activity. Patients who received 4 g 5-ASA daily demonstrated significant declines in disease activity index within three weeks of therapy and maintained improvement until the end of the stuuy. Although disease activity index declined for patients receiving 2 g 5-ASA daily, these changes did not reach statistical significance when compared to placebo-treated patients. On a five point scale (much improved, somewhat improved, unchanged, somewhat worse, much worse) the physician's global assessment mirrored the changes in disease activity index. Patients randomized to receive 4 g 5-ASA tablets were consistently noted as being either much or somewhat improved compared to placebo-treated patients. Side effects were few and minor and 52% (4 g 5-ASA), 42% (2 g 5-ASA) and 37% (placebo) of patients had no complaints. Headache was the most commonly cited adverse reaction for 6.9% (4 g 5-ASA) and 9.4% (2 g 5-ASA) of treated patients but 3.5% of placebo-treated patients also complained of headache. In conclusion in this randomized double-blind, placebo controlled study, patients with active ulcerative colitis randomized to 4 g 5-ASA per day noted improvement in disease activity as measured by disease activity index and physician's global assessment when compared to placebo-treated patients. ln contrast, patients who received 2 g 5-ASA daily did not demonstrate significant differences compared to the placebo group.

scholarly journals Effect of local use of extractum of curcumin in Сrohn’s disease experiment

2020 ◽  
pp. 133-140
Author(s):  
M. V. Osikov ◽  
E. V. Simonyan ◽  
A. E. Bakeeva
Keyword(s):  
Clinical Symptoms ◽  
Activity Index ◽  
Clinical Status ◽  
Clinical Signs ◽  
Disease Activity Index ◽  
Aminosalicylic Acid ◽  
Trinitrobenzenesulfonic Acid ◽  
Turmeric Extract ◽  
Local Use ◽  
Rectal Suppositories

The aim was to study the effectiveness of the use of turmeric extract in the composition of the original rectal suppositories in experimental Crohn’s disease (CD) based on the assessment of the clinical picture and indicators of the immune status.Materials and methods. The work was performed on 70 rats of the Wistar line. CD was unduced by the rectal administration of a trinitrobenzenesulfonic acid solution, rectal suppositories with 0.000075 mg of curcumin based on an alcohol solution of rhizome extract with turmeric roots were used after 12 hours for 7 days, in the comparison group rectal suppositories with 50 mg of 5-aminosalicylic acid were used (5-ASA). To assess the clinical status, the Disease activity index scale was used, the population spectrum of leukocytes, CD3 + and CD45RA + lymphocytes, the concentration of IgG, IgM, IL-23 on the 3, 5 and 7 days of the experiment were determined.Results: In CD, the clinical signs of the disease progress from 3 to 7 days, the total number of leukocytes in the blood increases due to monocytes, lymphocytes, including CD3 +, CD45RA +, the concentration of IL-23, IgM, Ig G. Local use of turmeric extract in CD reduces the severity of clinical symptoms on days 5 and 7, restores the total number of leukocytes, lymphocytes, including CD3 +, the concentration of IgM on days 3, 5, 7, and IL-23 on days 5 and 7, partially restores serum concentration of IgG on the 3-rd, 5th, 7th day, IL-23—on the 3-rd day of observation. The eff ect of CD in the composition of rectal suppositories of turmeric extract is comparable to the eff ect of 5-ASA on the 3-rd, 5th, 7th day of observation in relation to the severity of clinical symptoms, the number of leukocytes, lymphocytes, CD3 + in the blood, the concentration of IgM and IgG; less pronounced in relation to the concentration of IL-23 on day 3.Conclusion. The clinical and immunological efficacy of local application of turmeric extract every 12 hours as part of the original rectal suppositories in experimental CD has been demonstrated, comparable with the use of rectal suppositories with 5-ASA. 

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