Study on the Clinical Effect of Ranitidine Combined with Omeprazole in the Treatment of Peptic Ulcers

Materials Express

Study on the clinical effect of ranitidine combined with omeprazole in the treatment of peptic ulcers

Ying Liu and Yanping Tang∗ Department 2 of Gastroenterology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital (Tianjin Nankai Hospital), Tianjin 300100, PR China

ABSTRACT The clinical safety and efficacy of a novel pharmaceutical material (ranitidine combined with omeprazole) for treating peptic ulcers was analyzed using gastroscopy. The subjects were from the Department of Gastroen- terology, Nankai hospital, Tianjin, China. Gastroscopy was performed from March 2017 to March 2018. A 100 Article eligible patients with gastric ulcers were selected. The patients with peptic ulcers were randomly divided into two groups with 50 patientsIP: each. 192.168.39.151 For the control On: groupSun, ,03 150 Oct mg 2021 ranitidine 06:11:32 was administered orally, twice a Copyright: American Scientific Publishers day before meals, for four weeks. For the combinedDelivered group,by Ingenta 150 mg ranitidine was administered orally, twice a day before meals, along with 20 mg omeprazole once a day, for four weeks. The clinical efficacy of the therapy, disease recurrence, and adverse reactions were compared between the two groups. The antacid effect of combined therapy was stronger and longer lasting when compared with the control group (P<0.05). After six months of follow-up, the Helicobacter pylori (HP) clearance in the combined treatment group was more efficient than in the control group (P<0.05). Serious adverse reactions were not found in both the groups. Ranitidine combined with omeprazole is effective and safe in the treatment of peptic ulcers and worthy of clinical application. Keywords: Peptic Ulcer, Ranitidine, Omeprazole, Clinical Efficacy, Adverse Reactions.

1. INTRODUCTION Ranitidine can be used in the treatment of benign gas- Peptic ulcers are a common disease of the digestive sys- tric ulcers [12–14], duodenal ulcers, postoperative ulcers, tem, which result from the increased invasion of gastric reflux esophagitis, gastrointestinal bleeding, pancreatic acid [1–5], the hypofunction of mucosal defense, and the ulcer syndrome (zhuoyei’s syndrome), and the preven- synergistic damage by Helicobacter pylori (HP) [6, 7]. tion of non-steroidal anti-inflammatory drug-induced ulcer. It has been proven that HP is the key factor for the occur- It can also improve the level of factor VIII in patients with rence and recurrence of peptic ulcers [8]. Therefore, the mild and moderate hemophilia [12–14]. Ranitidine may be successfully eradication of HP to prevent the spread of more suitable for elderly patients who cannot tolerate the peptic ulcers is the key to curing the disease and reduc- adverse reactions of cimetidine and the patients who need ing their incidence rate. The author used omeprazole com- to take many kinds of drugs (especially the drugs affected bined with famotidine and ranitidine alone in the treatment by cimetidine) [15–17]. of peptic ulcer, compared the clinical efficacy of the two Omeprazole is a new, effective, and safe anti-peptic treatment schemes, in order to provide a reference for the ulcer drug. Chemically, it is a benzomitrazole deriva- treatment of peptic ulcer [9–11]. tive [18–20]. Omeprazole is lipid soluble and has similar physical and chemical properties to its parent molecule. In the acid environment, the easy Xuji is distributed in the ∗Author to whom correspondence should be addressed. membrane of gastric mucosal wall cells. Omeprazole was

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converted into the active form of Sulfinamide in the acidic drug reactions were looked out for. All patients were asked condition, and then the activity of the protein was inhib- to eat regularly. Before and after treatment, three routine ited by the irreversible binding of the disulfide bond with examinations including liver and kidney function and elec- the proton pump in the secretory membrane of the parietal trocardiogram were performed. cell. Thus, omeprazole is also known as a proton pump blocker [21]. 2.3. Detection Method HP detection: before and after treatment, each patient was 2. MATERIALS AND METHODS examined by gastroscope and two pieces of antrum tissue were taken. One piece was fixed with 10% formaldehyde 2.1. Research Object solution followed by preparation of paraffin sections and The subjects were from the Department of Gastroen- silver staining. The other piece was examined by rapid ure- terology, Nankai hospital, Tianjin. From January 2017 to ase test and some suspicious cases were tested by breath March 2018, the subjects were examined by gastroscopy. test. If one of the two tests are positive then HP infec- A 100 eligible patients with gastric ulcer were selected, tion will be confirmed in those cases. But if both tests 100 patients with peptic ulcers were randomly divided are negative the cases will be considered negative for HP into two groups, each group was randomly divided into infection. Detection of pH value in the stomach: insert 50 people. All patients did not take antacids, antibiotics, the corrected pH electrode into the stomach through the and bismuth for four weeks before the beginning of the nose, and observe the change of pH value in the stomach. treatment. Their liver and kidney functions were normal The recording times were 09:00–22:00 in the daytime and and without serious complications, such as pyloric infarc- 22:00–08:00 in the night. tion and gastrointestinal perforation. Pregnant and lactat- ing women along with drug allergy patients were excluded 2.4. Efficacy Criteria from the study. The patients were randomly divided into two groups: the combination group and ranitidine group. Gastroscopy was used for the evaluation criteria. The eval- The 48 patients in the combined treatment group were uation criteria were further classified as follows: (I) sig- 46.8 ± 20.5 years old, comprising 25 cases of duodenal nificant effect: ulcer healing, surrounding inflammatory IP: 192.168.39.151 On: Sun, 03 Oct 2021 06:11:32 ulcers, 19 cases of gastric ulcers, and 4 cases of com- reaction disappears, local scar tissue is replaced, and show- Copyright: American Scientificing new Publishers epithelial coverage; (II) effective: the ulcer length pound ulcers. The 47 cases in the ranitidine groupDelivered were by Ingenta 46.0 ± 21.8 years old, comprising 26 cases of duodenal is shortened by more than 50%; and (III) ineffective: the ulcers, 17 cases of gastric ulcers, and 4 cases of com- ulcer length is shortened by less than 50% or observed to have increased in length instead. Article pound ulcers. There was no significant difference between the two groups (P>0.05). The basic data of patients are shown in Table I. 2.5. Statistical Method Data were analyzed by SPSS11.0 statistical software and P< 2.2. Treatment Methods counting data were tested. 0.05 was statistically For the control group, 150 mg ranitidine was adminis- significant. tered orally, twice a day before meals, for four weeks. For the combined group, 150 mg ranitidine was adminis- 3. RESULTS AND DISCUSSION tered orally, twice a day before meals, along with 20 mg 3.1. Characterization of Ranitidine omeprazole once a day, for four weeks. The clinical effi- Dissolve 200 g (0.48 mL) of ranitidine hydrochloride in cacy, disease recurrence, and adverse reactions, of the two 300 mL of water, stir and add 1100 mL of saturated groups were compared. The above drugs were taken early sodium carbonate solution for reaction. The reaction solu- and before supper. The course of treatment in both groups tion was extracted with 300 mL chloroform. Wash the was four weeks and all were followed up for six months. chloroform extract with water several times. Add 100 mL The symptoms and signs were first recorded 72 hours after of ethyl acetate and 200 mL of petroleum ether, crystal- taking the medicine for the first time and then once a week. lize and filter by suction, wash the filter cake with a small The blood routine was measured once and signs of adverse amount of ethyl acetate-Petroleum Mimi, dry and obtain 157 g of white like powder solid, with a yield of about 88%, TMP: 67–70 C (Fig. 1). Table I. The basic conditions of the two groups of patients. 3.2. Characterization of Omeprazole Duodenal Gastric Compound ulcer ulcer ulcer Slowly add concentrated sulfuric acid (48 mL), stir and heat to 90 C, drop and add the mixed acid composed of Joint group 25 19 4 Ranitidine group 26 17 4 concentrated sulfuric acid (70 mL) and 65% nitric acid (82.6 mL, 1.19 mol), drop for 1.5 h, and conduct heat

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Fig. 1. Molecular formula of ranitidine. preservation reaction for 5 h. Cool to 0 C and extract with ethyl acetate. Ethyl acetate phase is poured into ice water (1 L), 5% sodium carbonate solution is added to adjust to neutral, standing and layering, the organic phase is dried with anhydrous magnesium sulfate, filtered, and the filtrate is concentrated to dry to obtain light yellow Fig. 4. Changes of pH value before and after treatment in control solid 3 (68.5 g, 94.19%), TMP: 69.71 C (Literature 6: group (1) and treatment group (2). yield 95%, 68–70 C). Figure 2 shows the chemical structure of omeprazole. Figure 3 shows the SEM characterization of omeprazole. As can be seen from the figure, 3.4. Group Curative Effect and Eradication Situation omeprazole molecules stack on top of each other, showing Comparing the two groups after treatment on eradication an irregular peak-like structure. rate, ulcer healing rate, and recurrence rate after half a year showed that the combined treatment group was signifi- P< 3.3. Difference of pH Value cantly better than ranitidine group ( 0.05). The efficacy and HP eradication of the two groups were also compared Before administration of the drugs the difference in pH Article (Figs. 6–7). between the two groups was not statistically significant (P>0.05; Fig. 4). The arrivalIP: time 192.168.39.151 of gastric pH > On:3in Sun, 03 Oct 2021 06:11:32 the combined treatment group was shorterCopyright: than thatAmerican in the Scientific3.5. Discussion Publishers Delivered by Ingenta ranitidine group (P<0.05). See Figure 5. The duration of Peptic ulcers are a common and frequently occurring dis- pH > 4 was compared between the two groups, and the ease. About 10–12% of people have peptic ulcers. Roberts group leader of the combined treatment group was raniti- et al. found that antacids and drugs for eradicating HP are dine group (P<0.05). important drugs for the treatment of gastric or duodenal ulcers [22–24]. The occurrence of ulcers is mainly related to the secretion of nocturnal acid. The inhibition of nocturnal acid is more important than that of nocturnal acid. Omeprazole can specifically act on the secretory micro- tubules of the parietal cells and the tubular vesicles in the cytoplasm, i.e., the location of the proton pump i-k-atpase

Fig. 2. Molecular formula of omeprazole.

5 µm

Fig. 5. Comparison of drug arrival time between control group (1) Fig. 3. SEM characterization of omeprazole. and treatment group (2).

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with famotidine is also signiﬁcantly better than ranitidine in ulcer hemostasis [29, 30]. Compared with ranitidine group, omeprazole combined with famotidine can effec- tively eradicate HP (91.7%) and improve ulcer healing rate (93.8%). The results were similar to those of Yumei et al. who used omeprazole and famotidine to treat 48 patients for four weeks with HP positive peptic ulcers (96%) and HP (92%). In addition, in terms of ulcer recurrence, the recurrence rate of HP infection in in 6 months for omeprazole plus famotidine was 2.1% and that for ranitidine alone was 20.8%.

4. CONCLUSION The classical treatment of peptic ulcers includes inter- Fig. 6. Number of relapses within one month between treatment group mittent therapy, maintenance therapy, and symptom self- (1) and control group (2). monitoring therapy. However, these are very complicated and difficult to master and adhere to. It can be seen from alcohol of the parietal cells of the stomach, which is con- the results of this study that omeprazole combined with verted into the form of sulfonamide, irreversibly combines ranitidine is effective and safe in the treatment of peptic with the sulfhydryl group of the proton pump through the ulcers, especially the peptic ulcers with HP infection. disulfide bond, inhibits the activity of h-k-atpase, blocks the last step of the secretion of gastric acid, and divides Acknowledgment: I would like to thanks the guidance the gastric acid [25–27]. and support from my Doctoral supervisor—Professor Li Ranitidine is a selective H2 receptor antagonist of the Ping, and also thanks the support to my research from third generation. It has an obvious inhibitory effect on the department 2 of gastroenterology, Tianjin Integrated Tra- secretion of gastric acid and pepsinIP: 192.168.39.151 and its effects last On: for Sun, ditional03 Oct 2021 Chinese 06:11:32 and Western Medicine Hospital (Tianjin Copyright: American ScientificNankai Publishers Hospital). We thank the participants and volun- a long time. It can also increase the blood flowDelivered of gastric by Ingenta mucosa and strengthen its defense mechanism [28]. Com- teers who took part in this work or offered help especially pared with ranitidine, famotidine was five times stronger the Jiangsu Provincial Center for Disease Control and Pre- vention. This research was financially supported by NSFC

Article than ranitidine. In this study, omeprazole combined with famotidine showed a strong and lasting antacid effect: the (Grant No. 81573737). duration of pH > 3 in the stomach or pH > 4 at night was longer than that of ranitidine alone (P<0.05). In addi- References and Notes tion, Reveiz et al. reported that the hemostasis effect is 1. Hou, Y.L. and Liu, Q., 2014. Clinical effects of rabeprazole, omepra- good when the gastric acid is inhibited to keep the pH zole or ranitidine combined with amoxicillin and clarithromycin value above 4–5, and the best hemostasis is when the in treatment of peptic ulcer. World Chinese Journal of Digestol- pH value is above 6. Therefore, omeprazole combined ogy, 22(22), pp.3208–3213. 2. Lanas, A., Artal, A., Blás, J.M., Arroyo, M.T., Lopez-Zaborras, J. and Sáinz, R., 1995. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. Journal of Clinical Gastroenterology, 21(2), pp.103–106. 3. Díaz Rubio, M., Sainz Samitier, R., Díaz de Rojas, F., Malagelada, J.R., Pajares, J.M., Rodrigo, J.M., Vilardell, F., Ruiz Ferrán, J., Bamberg, P., Segura, J., Guarner, L., Taxonera, C., Gravalos, R.G., Gomollon, F., Bixquert, M., Castello, M., Aparicio, P.G. and Vickers, C., 1991. Comparative multicentric study of omeprazole versus ranitidine in the treatment of duodenal ulcer. Revista Espanola De Enfermedades Digestivas, 80(1), pp.12–16. 4. Kager, L., Lindberg, G., Nilsson, L.H., Seensalu, R., Backman, L., Granström, L., Kollberg, B., Sidenvall, L., Moberg, S., Sörstad, J., Reichard, H., Westergaard, P., Olsson, J.E., Lindholmer, C., Fellander, G., Thor, K., Hellstrom, M., Bergenstrand, K., Fenyo, G., Bergstrand, O., Nystrom, B., Hernqvist, H. and Hallberg, D., 1991. The effect of omeprazole and ranitidine on ulcer healing, relief of symptoms, and incidence of adverse events in the treatment of duodenal ulcer patients. Hepato-Gastroenterology, 38(4), pp.287–290. 5. Sung, J.J.Y., Kuipers, E.J. and El-Serag, H.B., 2009. Systematic Fig. 7. Number of ulcers healed in one month in the control group (1) review: The global incidence and prevalence of peptic ulcer disease. and treatment group (2). Alimentary Pharmacology and Therapeutics, 29(9), pp.938–946.

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Received: 13 February 2020. Accepted: 16 March 2020.

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