RU2730483C1 - Method of preparing a pharmaceutical gel composition for treating proctologic diseases (versions) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to a method for preparing a pharmaceutical gel composition for treating hemorrhoids and anal fissures. Method of preparing a pharmaceutical gel composition for treating hemorrhoids and anal fissures containing: methyluracil, nifedipine, lidocaine in a certain ratio, in which in order to manufacture a ready pharmaceutical gel composition, it is necessary to prepare: gel containing methyluracil and lidocaine, by mixing methyluracil, lidocaine, carbopol, ethylenediaminetetraacetic acid, nipagin and triethanolamine with addition of water; nifedipine solution by mixing nifedipine with 96 % ethanol and polyethylene glycol-400 while thoroughly stirring; then, with thorough stirring, the nifedipine solution is added to the gel containing methyluracil and lidocaine to form a pharmaceutical gel composition (versions).

EFFECT: method described above simplifies preparation of a composition for treating hemorrhoids and anal fissures, having a stronger analgesic effect, with minimal reduction of therapeutic effect.

2 cl, 4 ex

Description

The present invention relates to medicine, namely to pharmacological compositions for the treatment of proctological diseases and methods for their preparation.

The pharmacological composition prepared by the proposed method can be used for the treatment of chronic hemorrhoids, acute manifestations of hemorrhoids (all stages), anal fissures (fissures), traumatic injuries of the anus and rectum, sphincter, postoperative rehabilitation of persons who have undergone treatment for hemorrhoids, polyps, papillomas, condylomas surgical methods, pathological changes in hemorrhoids, as an anesthetic and relaxing agent of the anorectal region, irritation of the mucous membrane of the anal canal, relieving sphincter spasms, in mono- and complex therapy of proctological diseases such as: proctitis, paraproctitis, rectal cancer, anal cancer, proctosigmoiditis, rectal fistulas, inflammatory processes of the anal canal, cryptitis, megacolon, rectal fibroma.

All clinical manifestations of pathological changes in hemorrhoids (rectal diseases) are referred to as hemorrhoids. There are about 118 people with hemorrhoids per 1000 adults. In Russia, about 5000 thousand operations are performed per year on patients diagnosed with chronic hemorrhoids. It is quite common due to the prevalence of chronic constipation, and in most patients, these two diagnoses are made simultaneously. In diseases of the rectum, there are 2 stages: acute and chronic. In the chronic stage, the manifestations of the disease are minimal, patients remain able to work, the use of simple measures allows you to periodically completely forget about the disease. In the acute stage, hospitalization is often required, with adequate treatment, the inflammation subsides and the disease again goes into the chronic stage. Rectal diseases often begin with a precursor period. There are unpleasant sensations in the anus, slight itching, some difficulty during bowel movements, this period lasts from several months to several years. Then bleeding occurs during bowel movements of varying intensity - from traces of blood on the stool to massive bleeding. In addition to bleeding, a common complaint is prolapse of internal hemorrhoids.

The anal fissure (fissure), a spontaneously arising linear or ellipsoidal defect of the mucous membrane of the anal canal and anoderm (the zone of transition of the mucous membrane into the skin), occupies the third place (up to 11-13%) in terms of patient turnover in the general structure of coloproctological diseases. The incidence of anal fissure is 20-30 cases per 1000 people of the adult population, the proportion of such patients in the structure of inpatients is 3-5%. There are two forms of the disease, which are stages of the same process and have features of the clinical course: acute anal fissure and chronic anal fissure. An acute anal fissure has a slit-like shape with smooth, even edges, its bottom is the muscle tissue of the internal sphincter of the anus. As a rule, the crack is located in the midline, more often on the posterior wall of the anal canal, less often on the anterior wall. In these places, there is a great danger of trauma to the mucous membrane during the act of defecation, and there are worse conditions for blood supply. An acute fissure is characterized by a triad of main complaints: pain during bowel movements, sphincter spasm, spotting from the anus. The pain is usually very intense and can last for a long time. Severe pain makes the patient delay defecation, which often leads to constipation. Pain is also associated with the second constant symptom of the disease - spasm of the anal sphincter. Arising during a bowel movement, it can last for days, until the next act of defecation. It is this symptom that plays a major role in the pathogenesis of the disease, closing a vicious circle - pain causes a spasm of the sphincter, the spasm increases pain and prevents the crack from healing. Permanent trauma to the mucous membrane defect by feces is accompanied by bleeding from the anus. Over time, an acute anal fissure becomes chronic. Its bottom and edges are covered with granulations with fibrinous bloom. With a long course of the disease, scar tissue grows along the edges of the crack with their compaction. In the area of the outer edge of the crack, a section of excess tissue develops - the anal "sentinel" tubercle. This development of scar tissue in the inner edge of the fissure can lead to the formation of a fibrous anal polyp. Subsequently, the tissues in the place of the crack are exposed to nutritional disturbances.

A large number of patent documents (RU2457806, RU2436537, RU2427331, RU2011119393, RU2332176, RU2296528, RU92006917) are known, which describe pharmaceutical compositions for the treatment of various manifestations of hemorrhoids, as well as relieving pain in rectum, with most of the patents related to surgical methods of treating the above diseases ... However, the priority of choice in non-invasive treatments is undeniable.

Compositions based on extracts of natural origin (RU2470651, RU2455978, RU2011133881, RU2225213, RU2207137, RU98101150) are quite common, however, as a rule, the action of such agents is slow, gradual, unable to relieve pain quickly, without resorting to analgesics and antispasmodics, in addition , there are not rare cases of severe allergic reactions. Plant extracts tend to be of variable composition and may differ from harvest season, changes in extraction techniques and processing of plant materials. Often, companies register them not as medicines, but as dietary supplements.

Known combined homeopathic preparations of anti-varicose action (RU2256462, RU2253471, RU2143271), which are used to treat complicated and uncomplicated varicose symptom complex, however, this direction in medicine is still controversial in terms of effectiveness, and homeopathic remedies are not medicinal.

In the last two decades, special attention has been paid to sphincter relaxants: drugs based on calcium antagonists (calcium channel blockers) and nitric oxide (NO) donors in the treatment of varicose veins of rectum. The best known calcium channel blockers are nifedipine and diltiazem. The effect of nifedirine was first studied and described by Chrysos in 1996 (Chrysos E. et al, Effect of nifedipine on recoanal motility, Dis. Colon. Rectam, 1996, 39, 212-216), later Carapetti investigated the possibility of local clinical use of diltiazem (Carapeti EA et al, Toppical diltiazem and bethanecol decrease anal sphincter pressure and heal anal fissures without side effect. Dis. Colon Rectum, 2000, 43, 1359-1362). Numerous works have been devoted to the study of the use of nitrates as NO donors to reduce pressure in the affected area. The most commonly used drugs include nitroglycerin, isosorbide di- and mononitrates, L-arginine (Loder AF et al, Reversible chemical sphinterotomy by local application glyceryl trinitrate, Br. J. Surg., 1994, 81, 1386-1389; Guillemot F. et al, Action in situ nitrogligerin on upper anal canal pressure of patients with terminal constipation. A pilot study., Dis. Colon Rectum, 1993, 36, 372-376; Schouten WR et al, Pathophysialogical aspects and clinical outcome of intra -anal application of isosorbide dinitrate in patients with chronic anal fissure, Gut, 1996, 39, 465-469; Griffin N. et al, Topical L-arginin gel lowers resting anal pressure: possible treatment for anal fissure, Dis. Colon Rectum, 2002, 45, 1332-1336).

In the patent environment, there are documents describing pharmacological compositions containing sphincter relaxants and a method for preparing such compositions. Japanese Patent JP2002356425 discloses a composition consisting of 0.5-10 wt% nifedipine, which may also contain betanicol. US patent US8048875 also describes a composition based on 2 wt.% Calcium channel blocker diltiazem or its salts for the treatment of diseases associated with high blood pressure or spasms in the anal region. US patent document US7189761 claims a composition based on nitric oxide donors with an active substance content of 0.01 wt% to 10 wt% for the treatment of anorectal diseases. In the work of the authors of international application WO2002 / 03973, formulations based on isosorbitol dinitrate with the possible addition of a calcium channel blocker (nifedipine) as an additional active ingredient. A drug based on calcium antagonists with the possibility of the presence of nitric oxide donors is claimed in US patent US20110263568. Several studies describe mixed compositions based on cholinergic agonists and calcium channel blockers (US20040028752, US20130079332).

The disadvantage of the above patents is the absence of anesthetic sphincter relaxants in the composition of these relaxants for the rapid local prevention of acute and chronic pain sensations associated with inflammation of hemorrhoids, damage to the mucous membrane of the anal canal and other diseases and pathological conditions of the anorectal region, as well as the absence of a regenerant in their main components. , which helps to accelerate the healing process.

The closest analogue of the proposed method is a method of preparing a composition for the treatment of proctological diseases (RU 2592366) containing 3.3-7.5 wt.% Methyluracil, 0.13-0.3 wt.% Nifedipine, 1.3-3 wt.% lidocaine, and 0.13-0.3 wt.% isosorbide dinitrate. However, the known method is difficult to implement and quite expensive. In addition, the analgesic effect of the composition prepared by the known method is insufficiently expressed.

Thus, there is a need for a simpler method for preparing a composition for the treatment of proctological diseases with a stronger analgesic effect, while minimizing the therapeutic effect.

The problem is solved by the proposed method for preparing a pharmaceutical gel composition intended for the treatment of proctological diseases, and containing 3.3-7.5 wt.% Methyluracil, 0.13-0.3 wt. % nifedipine, 1.3-5 wt.% lidocaine. When implementing the method, for the manufacture of 1000 g of a finished pharmaceutical gel composition, a gel containing methyluracil and lidocaine is prepared by mixing 33 - 75 g of methyluracil, 13 - 50 g of lidocaine, carbopol, ethylenediaminetetraacetic acid, nipagin and triethanolamine, with the addition of water to a total weight of 850 A solution of nifedipine is prepared by mixing 1.3 - 3 g of nifedipine with 96% ethanol, with the addition of polyethylene glycol-400 to the resulting solution, while the solution is thoroughly mixed and propylene glycol is added to it to a total weight of 150 g. Then, with thorough stirring, the solution nifedipine is added to a gel containing methyluracil and lidocaine to form a pharmaceutical gel composition.

Preferably, a method of preparing a pharmaceutical gel composition intended for the treatment of proctological diseases, and containing 5 wt.% Methyluracil, 0.2 wt. % nifedipine, 2 wt% lidocaine. When implementing the method, for the manufacture of 1000 g of a finished pharmaceutical gel composition, a gel containing methyluracil and lidocaine is prepared by mixing 50 g of methyluracil, 20-50 g of lidocaine, carbopol, ethylenediaminetetraacetic acid, nipagin and triethanolamine, with the addition of water to a total weight of 850 g. A solution of nifedipine is prepared by mixing 2 g of nifedipine with 96% ethanol, with the addition of polyethylene glycol-400 to the resulting solution, while the solution is thoroughly mixed and propylene glycol is added to it to a total weight of 150 g. Then, with thorough stirring, a solution of nifedipine is added to the gel containing methyluracil and lidocaine to form a pharmaceutical gel composition.

The technical result of the claimed invention is to simplify the method for preparing a composition for the treatment of proctological diseases with a stronger analgesic effect, with a minimum decrease in the therapeutic effect.

The pharmacological action of Methitluracil (dioxomethyltetrahydropyrimidine) is anti-inflammatory, leukopoietic, stimulating regeneration, reparative, wound-healing, immunostimulating. The drug has anabolic and anti-catabolic activity, accelerates the processes of cell regeneration; accelerates wound healing, stimulates cellular and humoral defense factors. It also has anti-inflammatory effects. A characteristic feature of the compounds of this series is the stimulation of erythro and especially leukopoiesis, in connection with which they are usually referred to the group of leukopoiesis stimulants. As a stimulant of leukopoiesis, methyluracil is prescribed for agranulocytic angina, alimentary-toxic aleukia, chronic benzene poisoning, leukopenia as a result of chemotherapy of malignant neoplasms, with X-ray and radiotherapy, and other conditions accompanied by leukopenia. It should be borne in mind that methyluracil, like other stimulants of leukopoiesis, is advisable to use in milder forms of leukopenia. With lesions of moderate severity, the use of hematopoietic stimulants is indicated only in case of resumption of impaired regeneration of blood cells. Also prescribed for sluggish healing wounds, burns, bone fractures. There is evidence of the effectiveness of methyluracil in gastric ulcer and duodenal ulcer and chronic gastritis. It is believed that the therapeutic effect is associated with the normalization of nucleic acid metabolism in the mucous membrane.

The following compounds can be used as a calcium channel blocker (calcium antagonist): amlodipine, anipamil, aranidipine, azelnidipine, barnidipine, benidipine, bepridil, darodipine, dildiazem, silnidipine, clevidipine, isradipine, efonidipine, lidipine, la felidipine, , mepirodipine, nicardipine, nifedipine, niludipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, perhexiline, tipamil, verapamil, pranidipine, their salts, solvates, hydrates, and a mixture of any of them.

The following substances can be used as a local anesthetic: proxymethacaine, bupivacaine, benzocaine, bromoanilide diethylaminopropanoic acid, articaine, oxybuprocaine, lidocaine, tetracaine, diclonin, dimethylaminoethyl n-butylaminobenzoic acid, or a mixture of procivacaine triplet, rocivacaine, roca

The pharmacological composition may additionally contain from 0 to 5 wt. % of an antibiotic derived from an imidazole, for example metronidazole, tinidazole, clotrimazole, secnidazole, ornidazole and others.

One of the advantages of the pharmaceutical composition for the treatment of hemorrhoids and anal fissure, prepared by the proposed method, is a synergistic effect between its active components and the achievement of a rapid therapeutic effect in comparison with known analogs, since the action of a calcium channel blocker provides a local vasodilatory effect and, as a consequence, a faster penetration of anesthetic and wound healing agent into the affected areas.

Any excipients can be used as auxiliary substances in the pharmaceutical composition to create a pharmaceutical composition in the form of a gel, ointment, suppositories, cream, suspended gel, lotion, for example water, polyethylene 400, propylene glycol, dimethyl sulfoxide, xanthanes, cellulose and its derivatives, vegetable oils , petrolatum, wax, polyvinylpyrrolidone, carbomers and their salts, thiethanolamine, benzalkonium chloride and others.

The pharmacological composition may contain gelling agents, stabilizers and preservatives.

Hydroxyethyl cellulose or sodium carboxymethyl cellulose or hydroxypropyl cellulose is used as a gelling base (gelling agent).

As a preservative, they are selected compatible with active substances and well-proven sodium salts of parabens that meet the requirements of the Pharmacopoeia, methylparaben, propylparaben, etc.). Other preservatives such as propylene glycol and the like can also be used.

As a stabilizer, the sodium salt of ethylenediaminetetraacetic acid used in the pharmaceutical industry can be used, an analogue is TRILON-B or another, similar in properties and action.

The possibility of carrying out the invention is illustrated by the following examples:

Example 1.

A method of preparing a gel containing 3.3 wt. % methyluracil, 0.13 wt. % nifedipine, 1.3 wt. % lidocaine.

Below is a step-by-step procedure for preparing 1000 g of gel.

1. The gel is prepared by mixing 33 grams of methyluracil, 13 grams of lidocaine, two grams of Carbopol (a mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with the addition of water to total weight 850 grams.

2. 1.3 grams of nifedipine was mixed with 10 ml of 96% ethanol. To the resulting solution was added 40 grams of polyethylene glycol-400. After thorough mixing, propylene glycol was added to the resulting solution to a total weight of 150 grams.

3. The nifedipine solution was added with vigorous stirring to the suspended gel containing methyluracil and lidocaine to form a pharmaceutical gel composition.

Test results of using a gel containing 3.3 wt. % methyluracil, 0.13 wt. % nifedipine, 1.3 wt. % lidocaine in patients with hemorrhoids and anal fissures.

100 tubes containing 50 grams of the gel prepared according to Example 1 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the use of the gel, recovery was observed in all cases (cessation of pain, bleeding, elimination or significant reduction in the edema of hemorrhoids, healing of anal fissures). No side effects were observed when using the gel. The majority of patients (approximately 58%) recover within 21 to 28 days, while the remaining 42% of patients recover within 29 to 45 days. At the same time, most of the patients (about 60%) noted a decrease in pain sensations already within the first three days of using the gel.

Example 2.

A method of preparing a gel containing 5 wt.% Methyluracil, 0.2 wt. % nifedipine, 2 wt% lidocaine.

Below is a step-by-step procedure for preparing 1000 g of gel.

1. The gel is prepared by mixing 50 grams of methyluracil, 20 grams of lidocaine, two grams of Carbopol (a mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with the addition of water to total weight 850 grams.

2. Two grams of nifedipine was mixed with 10 ml of 96% ethanol. To the resulting solution was added 40 grams of polyethylene glycol-400. The solution was thoroughly mixed. Propylene glycol is added to the resulting solution to a total weight of 150 grams.

3. The nifedipine solution was added with vigorous stirring to the suspended gel containing methyluracil and lidocaine to form a pharmaceutical gel composition.

Test results of using a gel containing 5 wt. % methyluracil, 0.2 wt. % nifedipine, and 2 wt. % lidocaine in patients with hemorrhoids and anal fissures.

100 tubes containing 50 grams of the gel prepared according to Example 2 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the use of the gel, recovery was observed in all cases (cessation of pain, bleeding, elimination or significant reduction in the edema of hemorrhoids, healing of anal fissures). No side effects were observed when using the gel. When using the gel prepared in accordance with example 2, the majority of patients (about 66%) recover within 21 to 28 days, while the remaining 34% of patients recover within 29 to 45 days. At the same time, the majority of patients (approximately 76%) noted a decrease in pain during the first three days of using the gel.

Example 3.

A method of preparing a gel containing 7.5 wt. % methyluracil, 0.3 wt. % nifedipine, 5 wt. % lidocaine.

Below is a step-by-step procedure for preparing 1000 g of gel.

1. The gel is prepared by mixing 75 grams of methyluracil, 30 grams of lidocaine, two grams of Carbopol (mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with the addition of water to total weight 850 grams.

2. Three grams of nifedipine was mixed with 10 ml of 96% ethanol. To the resulting solution was added 40 grams of polyethylene glycol-400. After thorough mixing, propylene glycol was added to the resulting solution to a total weight of 150 grams.

3. The nifedipine solution was added with vigorous stirring to the suspended gel containing methyluracil and lidocaine to form a pharmaceutical gel composition.

Test results of using a gel containing 7.5 wt. % methyluracil, 0.3 wt. % nifedipine and 5 wt. % lidocaine in patients with hemorrhoids and anal fissures.

100 tubes containing 50 grams of the gel prepared according to Example 3 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the use of the gel, recovery was observed in all cases (cessation of pain, bleeding, elimination or significant reduction in the edema of hemorrhoids, healing of anal fissures). No side effects were observed when using the gel. When using the gel prepared in accordance with example 3, the majority of patients (approximately 64%) recover within 21 to 28 days, while the remaining 36% of patients recover within 29 to 45 days. Moreover, approximately 81% of patients noted a decrease in pain during the first three days of using the gel.

Comparative example 4.

Was implemented a method for preparing a gel according to the closest analogue (RU 2592366), which contains 3.3 wt. % methyluracil, 0.13 wt. % isosorbide dinitrate, 0.13 wt. % nifedipine, 1.3 wt. % lidocaine.

Below is a step-by-step procedure for preparing 1000 g of gel.

1. The gel is prepared by mixing 33 grams of methyluracil, 13 grams of lidocaine, two grams of Carbopol (a mixture of carbomers), one gram of ethylenediaminetetraacetic acid (EDTA), two grams of Nipagin (propylparaben, antimicrobial additive, preservative) and 18.5 grams of triethanolamine with the addition of water to total weight 850 grams.

2. 1.3 grams of nifedipine was mixed with 10 ml of 96% ethanol. To the resulting solution was added 40 grams of polyethylene glycol-400. After thorough mixing, propylene glycol was added to the resulting solution to a total weight of 135 grams.

3. To five grams of a mixture containing 26 wt. % (1.3 grams) isosorbide dinitrate and 74 wt. % (3.7 grams) of lactose was added 10 grams of dimethisulfoxide (DMSO). The mixture was stirred until a clear solution was obtained.

4. The isosorbide dinitrate solution was added to the nifedipine solution.

5. The combined solution of isosorbide dinitrate and nifedipine was added with vigorous stirring to the suspended gel containing methyluracil and lidocaine to form a pharmaceutical gel composition.

Test results of using a gel containing 3.3 wt. % methyluracil, 0.13 wt. % isosorbide dinitrate, 0.13 wt. % nifedipine, 1.3 wt. % lidocaine in patients with hemorrhoids and anal fissures.

100 tubes containing 50 grams of the gel prepared according to Example 1 were distributed to patients suffering from hemorrhoids and anal fissures. 100 patients applied the gel 2-3 times daily for 21 to 45 days. As a result of the use of the gel, recovery was observed in all cases (cessation of pain, bleeding, elimination or significant reduction in the edema of hemorrhoids, healing of anal fissures). No side effects were observed when using the gel. The majority of patients (approximately 61%) recover within 21 to 28 days, while the remaining 39% of patients recover within 29 to 45 days. Moreover, only 59% of patients noted a decrease in pain during the first three days of using the gel.

Thus, the proposed method for the preparation of the gel, in comparison with the closest analogue, makes it possible to simplify the preparation procedure by reducing it by two operations and, accordingly, to reduce the preparation time of the composition, as well as to reduce its cost.

Moreover, the use of the proposed composition, in comparison with the closest analogue, has only a slightly reduced objectively observed therapeutic effect, which, nevertheless, significantly exceeds the effect of other known drugs.

In addition, when using this drug, patients noted a faster and more significant reduction in pain, which also has a positive effect on overall well-being and contributes to a faster recovery.

When using a comparative composition that did not contain methyluracil, the distribution of recovered patients by treatment time was different. Thus, the majority of patients (approximately 59%), out of the number of patients who recovered up to 45 days, 60% of patients who used the comparative composition, which did not contain methyluracil, recovered over a longer period of 29 to 45 days. With an increase in the duration of treatment with a comparative composition over 45 days, the overall percentage of patients with complete recovery increases slightly. Moreover, only 47% of patients noted a decrease in pain in the first 3 days of using the drug.

According to the test results, the optimal ratio of the components that make up the composition was determined. As studies have shown, with a decrease or increase in the concentration of active components from the stated limits, an increase in the therapeutic properties of the composition does not occur. That is, any deviations from the optimal ratio of components do not allow obtaining the desired therapeutic effect. In addition, the qualitative composition of the claimed composition is selected empirically and the absence of any ingredient in its composition does not allow achieving the result obtained when using the claimed composition.

Thus, the use of a complex pharmacological composition made by the proposed method and based on 3.3-7.5 wt. % methyluracil, 0.13-0.3 wt. % nifedipine and 1.3-5 wt. % lidocaine, by patients suffering from hemorrhoids and anal fissures, made it possible to enhance and accelerate the achievement of the therapeutic effect, in comparison with the composition without methyluracil.

Other interpretations and variations of the present invention are possible, which do not contradict the claims of the patent in terms of a method for preparing a pharmaceutical composition, a type of pharmaceutical composition, a method and scope of application. In particular, on the basis of the proposed composition comprising 3.3-7.5 wt. % methyluracil, 0.13-0.3 wt. % nifedipine and 1.3-5 wt. % local anesthetic ointments, suppositories, creams, lotions, suspensions can be prepared, which can be applied locally for the treatment of chronic hemorrhoids, acute manifestations of hemorrhoids (all stages), anal fissures (fissures), traumatic injuries of the anus and rectum, sphincter, postoperative rehabilitation of persons who have undergone treatment of hemorrhoids, polyps, papillomas, condylomas by surgical methods, pathological changes in hemorrhoids, as an anesthetic and relaxing agent of the anorectal region, irritation of the anal mucosa, relieving sphincter spasms, in mono- and complex therapy of proctological diseases, such as : proctitis, paraproctitis, rectal cancer, anal canal cancer, proctosigmoiditis, rectal fistulas, inflammatory processes of the anal canal, cryptitis, megacolon, rectal fibroma.

Claims (8)

1. A method of preparing a pharmaceutical gel composition intended for the treatment of hemorrhoids and anal fissures and containing 3.3-7.5 wt.% Methyluracil, 0.13-0.3 wt.% Nifedipine, 1.3-5 wt.% Lidocaine , in which for the manufacture of 1000 g of the finished pharmaceutical gel composition is prepared: - a gel containing methyluracil and lidocaine by mixing 33-75 g of methyluracil, 13-50 g of lidocaine, carbopol, ethylenediaminetetraacetic acid, nipagin and triethanolamine with the addition of water to a total weight of 850 g; - a solution of nifedipine by mixing 1.3-3 g of nifedipine with 96% ethanol with the addition of polyethylene glycol-400 to the resulting solution, while the solution is thoroughly mixed and propylene glycol is added to it to a total weight of 150 g; - then, with thorough mixing, the nifedipine solution is added to the gel containing methyluracil and lidocaine to form a pharmaceutical gel composition. 2. A method of preparing a pharmaceutical gel composition intended for the treatment of hemorrhoids and anal fissures and containing 5 wt.% Methyluracil, 0.2 wt.% Nifedipine, 2 wt.% Lidocaine, in which for the manufacture of 1000 g of the finished pharmaceutical gel composition is prepared: - a gel containing methyluracil and lidocaine by mixing 50 g of methyluracil, 20 g of lidocaine, carbopol, ethylenediaminetetraacetic acid, nipagin and triethanolamine with the addition of water to a total weight of 850 g; - nifedipine solution by mixing 2 g of nifedipine with 96% ethanol with the addition of polyethylene glycol-400 to the resulting solution, while the solution is thoroughly mixed and propylene glycol is added to it to a total weight of 150 g; - then, with thorough mixing, the nifedipine solution is added to the gel containing methyluracil and lidocaine to form a pharmaceutical gel composition.