RU2400231C2 - METHOD OF TREATING STOMACH AND DUODENUM DISEASES CAUSED BY Helicobacter pylori IN COMBINATION WITH CARRYING OUT THERAPEUTIC PROCEDURES IN ORAL CAVITY - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gastroenterology, and can be used for treatment of stomach and duodenum diseases caused by Helicobacter pylori. For this purpose slurried mixture of clarithromicin and amoxicillin is introduced. Simultaneously in oral cavity applied are medicinal hardening parodontal bandages or polymer films with said antibacterial medications.

EFFECT: method allows to eliminate Helicobacter pylori both in stomach and in oral cavity, prevent further infecting of stomach and eliminate side effects caused by traditional therapeutic methods.

2 ex

Description

The present invention relates to medicine, namely to gastroenterology, and can be used to treat diseases of the stomach and duodenum caused by Helicobacter pylori.

Traditionally, eradication therapy is used to treat this infection, consisting of an antisecretory drug, two antibacterial drugs, to which a bismuth preparation can be added. Dosages and dosage regimen of eradication therapy are shown below:

a) omeprazole in a dose of 20 mg (or lansoprazole 30 mg or pantoprazole 20 mg) 2 times a day for 7-14 days;

b) clarithromycin 250-500 mg 2 times a day for 7-14 days;

c) amoxicillin 1000 mg (or metronidazole 500 mg or furazolidone 100 mg) 2 times a day for 7-14 days;

d) preparations of bismuth salts, for example, De-nol 1 tablet (120 mg) 4 times a day or 2 tablets 2 times a day for 7 or 10 or 14 or 28 days [Helicobacter pylori: revolution in gastroenterology. Ed. Acad. RAMS V.T. Ivashkina, prof. F.Megro, T.L. Lapina. - M., Triad-X, 1999, 255 p .; Lapina T.L. Modern regimens of eradication therapy of Helicobacter pylori infection. / Materials of the satellite symposium in the framework of the VIII Russian National Congress "Man and Medicine". - 2001. - P.84.]. Such a scheme, unfortunately, has several disadvantages.

The main ones include the following:

1) almost all drugs used for eradication (with the exception of bismuth salts) show their therapeutic effect not directly in the pathogen habitat, but, bypassing it, begin to act only after absorption in the small intestine into the systemic circulation and diffusing from the capillary network of the mucous membrane through the basement membrane of the epithelium;

2) the introduction of large doses of antibiotics into the body to treat a limited process localized in a small area of the gastric mucosa, since the minimum amount of drugs is delivered through the systemic bloodstream to the direct location of the pathogen, while the main dose of the drug is distributed in the biological environment of the body, where therapeutic effect;

3) the adverse effect of antibacterial drugs on the normal microflora of the body, which often leads to the development in the intestine of a syndrome of excessive bacterial growth of varying severity;

4) significant individual differences in the speed and completeness of absorption of drugs, which depend on a large number of factors, such as: the condition of the mucous membrane and submucosal layer of the small intestine, the intensity of blood flow in it, taking the drug at different periods of digestion (before meals, after meals, in the inter-digestive period), individual differences in detoxification and biotransformational ability of the liver;

5) the high cost of a course of eradication therapy.

In the practice of a gastroenterologist, there are cases when, after eradication of Helicobacter pylori, the success of which is confirmed after 4 weeks or more, after the end of treatment with morphological or non-invasive methods, when this patient is re-treated after 6-12 months, Helicobacter pylori is again revealed. Such repeated infections can be due to two factors:

1) re-infection with constant contact with carriers of infection;

2) penetration of Helicobacter pylori into the stomach from other places of persistence, where the pathogen was not available for exposure to antibacterial drugs used in previously conducted eradication.

Analysis of patient follow-ups showed that in more than half of cases, detection of HP in the stomach could not be explained by the first factor. Thus, an increase in the number of cases of final eradication must be sought in eliminating the second factor.

It is known that the causative agent of chronic gastritis and peptic ulcer - Helicobacter pylori - lives not only in the stomach, but also in other parts of the body: in the intestine [P.Ya. Grigoryev, E.P. Yakovenko Helicobacter pylori: gastritis, duodenitis (gastroduodenitis), peptic ulcer and other helicobacter-associated diseases // Russian Gastroenterological Journal. - 1999. - No. 4; V.A.Shkitin, A.I. Shpirna, G.N. Starovoitov Role of helicobacter pylori in human pathology // Clinical Microbiology and Antimicrobial Therapy. - 2002. - Volume 4, No. 2. - S.128-145], in the oral cavity [Kaspina A.I., Drozhzhina V.A., Kerzikov A.F., Kerzikov O.A. The effect of Helicobacter pylori infection on the condition of the oral mucosa // Institute of Dentistry No. 4 (21), December 2003 (Electronic document) http://dentalsite.solvay-pharma.ru/articles/article.aspx?id=2100 Verified on 30.08. 2008.] and the vagina [Eslick Guy D. Helicobacter pylori infection transmitted sexually via oral-genital contact: A hypothetical model // Sex. Transmitt. Infec - 2000. - Vol. 76. - N 6. - P.489-492]. Obviously, the probability of reinfection of the stomach from the oral cavity is many times higher than from other places of localization. Thus, in order to successfully treat Helicobacter pylori infection and prevent re-infection, the pathogen needs to be eradicated not only in the stomach, but also in the oral cavity.

In the literature there are indications of the possibility of migration of the pathogen from the oral cavity to the stomach [Tsimbalistov A.V., Robakidze N.S. Periodontal status of "Helicobacter pylori-infected peptic ulcer patients." Proceedings of the 6th Congress of the Dental Association of Russia. - Moscow, 2000. - S.255-257].

It was found that Helicobacter pylori can actively persist in periodontal pockets, in soft plaque, in patients' saliva. For successful treatment of periodontal diseases, it is necessary to get rid of a whole "bunch" of concomitant bacteria, including Helicobacter pylori. For this purpose, a comprehensive treatment was carried out, including eradication therapy according to the traditional method. [Kaspina A.I., Drozhzhina V.A., Kerzikov A.F., Kerzikov O.A. The effect of Helicobacter pylori infection on the condition of the oral mucosa // Institute of Dentistry No. 4 (21), December 2003 (Electronic document) http://dentalsite.solvay-pharma.ru/articles/article.aspx?id=2100 Verified on 30.08. 2008].

Descriptions of local treatment of Helicobacter pylori in the oral cavity in the available literature have not been found anywhere else.

The prior art methods for treating diseases of the mucous membranes of the oral cavity by applying the drug in the form of: gauze, cotton and film applications, dressings, injections [Periodontal disease: Atlas / NF Danilevsky, E. A. Magid, N. A. Mukhin, V.Yu. Milikevich; under the editorship of N.F.Danilevsky. - M .: Medicine, 1993. - 320 p.].

The disadvantages of injections include the following:

- soreness;

- invasiveness;

- the need for preliminary anesthesia;

- the likelihood of a hematoma at the injection site.

The disadvantages of gauze and cotton applications include the following:

- insufficient exposure time of the drug in the oral cavity;

- increase in the number of visits to the doctor;

- the use of applications is accompanied by the appearance of an unpleasant taste in the mouth, which creates additional inconvenience to the patient;

- most of the drug is washed off with saliva, which requires an additional increase in the dose of the drug.

One of the optimal methods of treatment in dentistry is the use of therapeutic hardening periodontal dressings [Periodontal disease: Atlas / NF Danilevsky, E. A. Magid, N. A. Mukhin, V. Yu. Milikevich; under the editorship of N.F.Danilevsky. - M.: Medicine, 1993. - 320 p.] Or applications using polymer films [Meet: Diplen-Denta films Electronic version of the professional Russian monthly newspaper Dentistry Today, 2002. - No. 5 (18) (Electronic document ) http://www.dentoday.ru/ru/content/archive/2002/5/l 9 / (Verified on 10/22/2008)].

The advantages of these techniques are as follows:

- a long exposure time of the drug;

- the possibility of a single use within 1-2 days;

- convenience for the patient (reducing the number of visits to the doctor, reducing the time of medical admission);

- minimal discomfort in the mouth while maintaining patient diction;

- lack of bad taste in the mouth.

However, when familiarizing ourselves with the methods of manufacturing and using the above-mentioned medical hardening periodontal dressings or polymer films, we never met the combined use of clarithromycin and amoxicillin, the main antibiotics used to eradicate Helicobacter pylori.

The task of the invention is to develop a comprehensive treatment that eliminates Helicobacter pylori in the stomach and in the oral cavity.

The technical result, which consists in eliminating these shortcomings in the treatment of diseases of the stomach and duodenum caused by Helicobacter pylori, is achieved through the local use of antibacterial agents in the stomach according to the patent of the Russian Federation No. 2265437 with the simultaneous use of therapeutic hardening periodontal dressings or polymer films containing the same antibacterial chemotherapy drugs.

The use of the method of treating Helicobacter pylori in the stomach according to RF patent No. 2265437 is not accompanied by side effects characteristic of traditional eradication therapy, and the use of therapeutic hardening periodontal dressings or polymer films in the oral cavity prevents the subsequent infection of the stomach.

The essence of the invention lies in the joint application of the methodology according to RF patent No. 2265437 and the use of therapeutic hardening periodontal dressings or polymer films containing amoxicillin and clarithromycin, which have a local bactericidal and bacteriostatic effect on Helicobacter pylori in the oral cavity.

The suspended mixture for oral administration is prepared according to the method described in the patent of the Russian Federation No. 2265437, by mixing for 10-15 minutes the required quantities of drugs with a suspension that has the ability to linger on the mucous membrane, previously crushed in a sterile porcelain or agate mortar.

A curing periodontal dressing is prepared ex tempore by mixing 5 g of zinc oxide, 5 g of dentin powder, 100 mg of clarithromycin, 200 mg of amoxicillin on a glass plate with the addition of the necessary amount of clove oil to a thick but plastic consistency. The prepared paste is put with a spatula or a trowel with the lingual and palatine, and then from the vestibular side on the dried gingival margin, in the interdental spaces, in the gingival pockets. The surface of the dressing is pressed tightly with a glove rubber glove or fingers on all sides and is modeled so that the cutting edges and chewing surfaces of the teeth are free, and the edges of the dressing do not reach the moving part of the gum. The dressing hardens within 6-8 minutes, is able to remain in compliance with the gentle regime up to 1.5-2 days.

A polymer film containing amoxicillin and clarithromycin at 0.1 mg / cm ² , films made according to the method of the USSR AS for No. 722214 from 05.15.78. "Adhesive film for medical purposes" and allows for a sustained flow of drugs to the localization of the pathogen in the oral cavity.

A comparative analysis of the prototype and the present invention shows that the common features are: the use of chemotherapeutic drugs (amoxicillin and clarithromycin) active against Helicobacter pylori.

Distinctive features are the simultaneous local use of these drugs in the lumen of the stomach and in the oral cavity.

The implementation of the proposed method is illustrated by the following examples.

Clinical example 1.

Patient D., 23 years old, diagnosis: chronic widespread superficial gastritis in the acute phase, in biopsy samples of the mucous membrane of the antrum of the stomach, a picture of active superficial gastritis with an abundance of Helicobacter pylori. Peptic ulcer of the duodenum in the phase of persistent remission, cicatricial deformity of the duodenal bulb. In the study of smears from gingival pockets and scrapings from the cheek mucosa, mixed flora was found, including Helicobacter pylori.

The treatment was carried out: omeprazole 20 mg 2 times a day for 10 days, clarithromycin and amoxicillin in a dose reduced 5 times from the prescribed treatment regimen in a suspension of aluminum and magnesium hydroxides (almagel), 5 ml 4 times a day in the inter-digestive period and at night for 10 days, with the simultaneous application of treatment hardening periodontal bandages every two days.

28 days after the end of treatment with repeated gastroscopy, chronic superficial gastritis was detected in the remission phase, and Helicobacter pylori was not found in the stomach and oral cavity.

Clinical example 2.

Patient B., 27 years old, diagnosis: chronic widespread superficial gastritis in the phase of decaying exacerbation, in biopsy samples of the mucous membrane of the antrum, a picture of moderately active superficial gastritis, Helicobacter pylori in moderation. On examination by a dentist, exfoliative glossitis and recurring cracks in the corners of the mouth, more often on the left, were found in this patient. From the anamnesis it was found that plaque in the tongue has been disturbing for more than 10 years, and recurring cracks in the corners of the mouth appear in the spring-autumn period over the past 6-8 years. The local treatment previously prescribed by dentists and dermatologists (rinses with herbal remedies, ointments) gave a short-term effect. Numerous mixed flora, including Helicobacter pylori, was found in smears from gingival pockets and in soft plaque.

The treatment was carried out: omeprazole 20 mg 2 times a day for 10 days, clarithromycin and amoxicillin in a dose reduced 5 times from the prescribed treatment regimen in a suspension of aluminum and magnesium hydroxides (almagel), 5 ml 4 times a day in the inter-digestive period and overnight for 10 days, with simultaneous daily application of therapeutic polymer films, which included amoxicillin and clarithromycin.

67 days after the end of treatment with repeated gastroscopy, chronic superficial gastritis was detected in the remission phase. In the stomach and in smears from the oral cavity Helicobacter pylori was not detected. The patient noted an almost complete disappearance of discomfort in the mouth, and when re-examined by a dentist, a significant improvement was found in the form of a cleansing of the mucous membrane of the tongue and epithelization of the cracks.

Claims (1)

A method of treating diseases of the stomach and duodenum caused by Helicobacter pylori using a suspended mixture of amoxicillin and clarithromycin, characterized in that in the treatment of Helicobacter pylori in the stomach, treatment hardening periodontal dressings or polymer films with the indicated antibacterial drugs are used.