RU2483721C1 - Tisolum-based pharmaceutical composition for treatment of anal fissures - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine and pharmacology and represents pharmaceutical composition for treatment of anal fissures, including base, medication which reduces spasms of smooth muscles, lidocaine, it contains tisolium-gel as base and nifedipine or nitroglycerin as medication, reducing spasm of smooth muscles, components of composition being in specified ratio in grams.

EFFECT: invention provides efficient treatment with reduction of concentration of active substances, reduction of side effects, and reduction of treatment terms.

7 ex

Description

The invention relates to medicine, and is intended for the treatment of acute and chronic anal fissures.

Anal fissure is a common disease of the anal canal, characterized by the formation of a linear defect of the anoderm mainly on the anterior or posterior wall of the anal canal, very rarely on the side wall. Women get sick more often than men. The characteristic location of anal fissures is explained by the structural features and blood supply of the anal canal [1, 2].

The main cause of anal fissure is constipation. Although in some cases, patients do not complain of difficulty defecating. Diarrhea, inflammatory changes in the anal canal of a different nature, the introduction of foreign bodies into the rectum, and also anal sex can also provoke the occurrence of an anal fissure. Anal fissure may be combined with hemorrhoids.

After the occurrence of an acute anal fissure, as a rule, its chronization occurs. At the same time, sclerosis of the edges of the crack is noted, the so-called upper and lower guard tubercles, histologically represented by parakeratosis, can form.

A key role in the pathogenesis of chronic anal fissure is played by spasm of the internal anal sphincter. Spasm - lack of relaxation of the anal canal during bowel movements. This leads to additional trauma to the anal fissure. A spasm disrupts blood circulation in the area of the anal fissure and, as a result, healing is worsened.

A spasmodic sphincter complicates bowel movements and worsens the healing conditions of the anal fissure. The main complaint made by patients is pain in the anal canal, arising or intensifying during bowel movements. The nature of the pain is usually intense. With chronic anal fissure, the intensity of pain decreases, but with exacerbations, the pain can become unbearable. Bleeding with anal fissure is not intense.

The choice of drugs for local therapy is great (proctosedil, religion advance, ultraproct, proctoglivenol, etc.), but none of them affects the increased tone of the internal anal sphincter - the main link in the pathogenesis of this disease. A number of compounds have the ability to reduce the tone of smooth muscle tissue and, in particular, the internal anal sphincter.

The use of botulinum toxin A injections for the treatment of anal fissures is known (6, 7, 8).

Botox is a specially treated botulinum toxin. The principle of its action is that it interrupts the flow of nerve impulses to the muscle, in the place where it was introduced. In the same way, when it is introduced into the anal sphincter, it relaxes and the spasm is eliminated. The effect of using Botox injections lasts up to three months. When using Botox, side effects can also be noted in the form of mild incontinence of stools or gases.

But when using botulinum toxin A injections to treat an anal fissure, allergic reactions of various severity are possible, up to anaphylactic shock, as well as complications of any invasive procedure:

- the possibility of infection by parenteral infections;

- local complications in the form of a hematoma, suppuration, etc.

The works of foreign scientists on the medical treatment of anal fissures are known, in which the possibility of eliminating the spasm of the anal sphincter using drugs containing nitroglycerin (4), nifedipine (3, 5) is presented. The duration of therapy reached 6-8 weeks.

The closest analogue adopted for the prototype is a medicinal composition containing vaseline as a base, nifedipine 0.3% as a drug that reduces smooth muscle spasms, and 1.5% as anesthetic, lidocaine (4). The duration of therapy is 6 weeks.

The well-known fatty system of the base - petroleum jelly prevents the penetration of medicinal substances introduced into it into biological tissues - the smooth muscles of the anal canal. At the same time, the effect of local treatment is significantly reduced. Vaseline negatively affects the epithelium of the anal canal, clogging the pores of the tissues, the concentration of the active substance when passing through the mucous and submucosal layers decreases sharply and its penetration rate decreases.

In addition, on the surface of the tissues of the anal canal, the fixation of vaseline-based drug compositions is difficult and its rapid outflow from the treatment surface is observed, and the effectiveness of the treatment depends on creating the necessary concentration of active substances in the muscle of the anal sphincter. As a result, the known analogue (prototype) uses a significant concentration of active substances in the medicinal composition - in the prototype nifedipine 0.3%, lidocaine 1.5%.

But it should be noted that nifedipine has some contraindications. When using nifedipine, redness of the face and skin, headache associated with a decrease in the tone of the vessels of the brain are often observed. Nausea, dizziness, swelling of the lower extremities, hypotension, and drowsiness are also possible. Drowsiness often develops. These contraindications require caution when prescribing the drug, in particular, with heart failure, severe arterial hypotension, pregnancy, breastfeeding. It is advisable to prescribe the drug in reduced doses under the mandatory control of blood pressure.

The task to which this technical solution is directed is to achieve treatment effectiveness while reducing the concentration of active substances that have significant contraindications, reducing treatment time by increasing the rate of penetration of the active substance into the anal fissure zone.

To solve the problem, a medicinal composition for the treatment of anal fissures, including a base, a drug that reduces spasms of smooth muscle, lidocaine according to the invention contains tizol gel as a base, and nifedipine or nitroglycerin as a drug that reduces spasms of smooth muscle the following ratio of components, g:

- a drug that reduces spasms of smooth muscle muscles, - 0.003-0.02

- lidocaine - 0.05-0.1

- tizol gel - up to 10

Tizol gel - Р№001667 / 01-010807, developed and manufactured by OLIMP LLC, Yekaterinburg - gel for external and local application, is a titanium glycerol solvate complex. Tizol gel, being a substance with a high penetrating ability, creates the necessary concentration of the active substance in the tissues. As a metal complex compound, tizol gel has an anti-inflammatory and antiseptic effect, ensuring its microbiological purity and sterility. The presence in the tizol of glycerol molecules bound to titanium atoms provides the drug with a good dehydrating, decongestant, local analgesic effect. The presence of water in the thisol molecule provides a moisturizing effect and antipruritic effect. Tizol gel accelerates reparative processes in the skin and reduces inflammation. Within 20-30 minutes, tizol gel is absorbed through the skin or mucous membrane, distributed in the subcutaneous tissue and underlying tissues to a depth of 4-5 cm. The duration of maintaining the therapeutic concentration in the focus is 8-12 hours. Tizol gel is not metabolized in the tissues of the body, excreted unchanged in urine, bile, in small quantities through the skin and mucous membranes for 20-24 hours. Not cumulated in the body.

The ability to penetrate deeply into tissues and the ability to serve as a conductor for other medicinal substances make compositions based on gel topisol unique drugs. The combination of gel topolysis and drugs that reduce the tone of the internal anal sphincter is a completely new approach to the treatment of anal fissures.

The drugs nifedipine or nitroglycerin relax the muscles of the anal sphincter and thereby relieve its spasm, which is one of the pathogenetic factors for the development of the fracture, since it leads to ischemia, i.e. impaired blood flow.

Tizol has good adhesion to biological tissues and after the penetration of the drug composition on the surface of the fissure of the anal canal, a thin microscopic, long-lasting, non-washable sterile film remains that protects the anal canal, including the anal fissure from mechanical damage, secretions.

Thus, tizol allows you to create microbiological purity and sterility of the anal area for a long time, has the ability to form immobilized systems that are more effective in local treatment with the medicinal substances introduced into it. The creation of an immobilized drug system that quickly penetrates into the treatment zone and is prolonged acting in the contact zone allows achieving the expected result at the minimum concentrations of drugs. Nitroglycerin, as well as nifedipine, causes side effects - headache, lowering blood pressure, therefore, a decrease in the concentration of these drugs in the drug composition when achieving the necessary treatment effectiveness with no side effects is important.

Pain relief, lack of discomfort is already present after 1-2 lubrications. In this case, the treatment of anal fissure is reduced to 2-3 weeks. A complete cure is achieved in the absence of relapse. A group of 64 patients with a diagnosis of chronic anal fissure was examined. Patients were recruited on the basis of the Health 365 clinic as they were approached in 2010. The group consisted of 28 men (age from 23 to 64 years, 39.2 ± 12.9) and 36 women (age from 22 to 70 years, 36.3 ± 13.4). In 39 (60.4%) cases, the crack was located on the back wall, in 25 (35.9%) cases - on the front. Two patients (3.1%) simultaneously had anterior and posterior cracks. In all cases, patients indicated the presence of pain associated with bowel movements. The intensity of pain ranged from subtle, arising from bowel movements, to intense, accompanied by stool fear. Blood in feces or on toilet paper was noted by 45 (70.3%) patients. An anal fissure was considered chronic with a disease duration of more than 2 months. and / or the presence of characteristic changes in the form of compaction of the edges of the anal fissure, the presence of guard tubercles. The presence or absence of previous treatment was not taken into account. All patients were prescribed conservative treatment. Food with a high content of plant fibers was recommended. If necessary, soft laxatives were prescribed - Forlax, Mukofalk. To lubricate the anal canal, the recommended drug composition, g

- a drug that reduces spasms of smooth muscle muscles - 0.003-0.02

- lidocaine - 0.05-0.1

- tizol gel - up to 10

It was recommended to apply the ointment three times a day. Local treatment was prescribed for a period of 2-4 weeks.

The treatment results were evaluated after 2-3 weeks from the start of therapy. Endoscopic examination (mainly rectoscopy) was carried out after epithelialization of the anal fissure. Patient complaints and examination data were taken into account. No complaints were noted in 62 (97%) patients. In these patients, complete epithelization of anal fissures was noted.

findings

According to the study, the use of a drug composition based on tisol for the treatment of anal fissure is highly effective. In 97% of cases, complete healing of anal fissures was noted.

The use of the claimed medicinal composition is illustrated by the following examples.

Example 1. Patient 34 years.

Complaints of intense pain in the anal canal during bowel movements, constipation. The duration of the disease is 4 months. Self-applied candles Relig within 10 days before the visit, without a pronounced effect.

On examination: the condition is satisfactory, the skin is of normal color, there are no enlarged lymph nodes, breathing is not difficult, the pulse of 72 beats per min is satisfactory, the tongue is moist, the stomach is soft, painless, and the liver is not palpated. Pasternatsky’s symptom is negative on the right and on the left.

Rectally: digital examination is not possible due to soreness. The sphincter is spasmodic. At 6 h, the dense lower edge of the anal fissure is determined.

Diagnosis: chronic posterior anal fissure, exacerbation.

Treatment was prescribed in the form of regulation of stool and local prescription of the drug composition, g: nifedepine - 0.02, lidocaine - 0.05, tizol gel - up to 10 with the recommendation to lubricate the anal canal 3 times a day for 1 month.

On rectal examination after 2 weeks: there is no sphincter spasm, a finger examination revealed that the anal fissure is epithelized for 6 hours, and there is no pain during the study.

Example 2. Patient 24 years.

Complaints of intense pain in the anal canal during bowel movements, stool fear. Ill acutely. Three days ago after defecation with dense feces, intense pains in the anal canal sharply arose, the pain subsided on its own after 1 hour, the next day the situation repeated. Previously, the colon was not examined, it was not treated on its own. I turned to a coloproctologist.

On examination: the condition is satisfactory, the skin is of normal color, there are no enlarged lymph nodes, breathing is not difficult, the pulse of 78 beats per min is satisfactory, the tongue is moist, the stomach is soft, painless, the liver is not palpated. Pasternatsky’s symptom is negative on the right and on the left.

Rectally: digital examination is not possible due to soreness. The sphincter is spasmodic. At 12 h, the lower edge of the linear tear is determined, the edges are loose.

Diagnosis: acute anterior anal fissure.

Treatment was prescribed in the form of regulation of stool and local prescription of the drug composition, g: nifedepine - 0.003, lidocaine - 0.1, actovegin - 0.05, tizol gel - up to 10 with the recommendation to lubricate the anal canal 3 times a day for 1 month. For an additional therapeutic effect, a wound healing substance, Actovegin, was added to the composition. Pain regressed for 4 days. Inspection after 2 weeks.

Upon rectal examination: there is no sphincter spasm, with a digital examination, an anal fissure is not determined, there is no pain during the examination.

Example 3. Patient 31 years.

Complaints of periodic intense pain in the anal canal during bowel movements, constipation, blood on toilet paper. Sick for six months. Self-applied candles with sea buckthorn oil for 2 weeks, noted a short-term effect. The colon has not previously been examined.

On examination: the condition is satisfactory, the skin is of normal color, there are no enlarged lymph nodes, breathing is not difficult, the pulse 72 min - satisfactory properties, the tongue is moist, the stomach is soft, painless, the liver is not palpated. Pasternatsky’s symptom is negative on the right and on the left.

Rectally: digital examination is not possible due to soreness. The sphincter is spasmodic. At 6 h, the lower edge of the anal fissure with a sentry tubercle is determined.

Diagnosis: chronic posterior anal fissure, exacerbation.

Treatment was prescribed in the form of regulation of stool and local prescription of the drug composition, g: nifedepine - 0.01, lidocaine - 0.05, tizol gel - up to 10 with the recommendation to lubricate the anal canal 3 times a day for 1 month.

When viewed after 2 weeks. All complaints were absent, the crack was completely epithelized, and there was no pain during rectal examination.

Example 4. Patient 54 years.

Complaints of scratching pain in the anal canal that occur during bowel movements, periodically constipation, periodically blood on toilet paper. Sick for 2 years. A year ago, she turned to a coloproctologist at the place of residence, a local ointment was proctosed. She noted a short-term effect. Passed rectoscopy.

On examination: satisfactory condition, increased nutrition, normal skin color, no enlarged lymph nodes, breathing is not difficult, pulse 72 min - satisfactory properties, tongue is moist, stomach is soft, painless, liver is not palpated. Pasternatsky’s symptom is negative on the right and on the left.

Rectally: the anal funnel is smoothed, the digital examination is painful, the sphincter tone is increased. At 6 h, an anal fissure with dense edges is determined, there is an upper guard tubercle, no other pathology is revealed at the height of the finger.

Diagnosis: chronic posterior anal fissure, exacerbation.

Treatment was prescribed in the form of regulation of stool and local prescription of the drug composition, g: nifedepine - 0.01, lidocaine - 0.1 actovegin - 0.03, tizol gel - up to 10 g with the recommendation to lubricate the anal canal 3 times a day for 1 month. For an additional therapeutic effect, a wound healing substance, Actovegin, was added to the composition.

Upon rectal examination after 3 weeks: there is no sphincter spasm, with a digital examination, an epithelized anal fissure is determined for 6 hours, there is no pain, all complaints have disappeared.

Example 5. Patient 38 years.

She complained of pain in the anal canal, aggravated by bowel movements, the appearance of blood on underwear. She got sick a week ago. A similar state for the first time. I was not treated on my own, I have not examined the colon before. Associates with an episode of intestinal toxicosis a week ago.

On examination: the condition is satisfactory, the skin is of normal color, there are no enlarged lymph nodes, breathing is not difficult, the pulse of 72 beats per min is satisfactory, the tongue is moist, the stomach is soft, painless, and the liver is not palpated. Pasternatsky’s symptom is negative on the right and on the left.

Rectally: digital examination is not possible due to soreness. The sphincter is spasmodic. At 12 h, the lower edge of the anal fissure is determined, the edges are loose.

Diagnosis: acute anterior anal fissure.

Treatment was prescribed in the form of regulation of stool and local prescription of the drug composition, g: nitroglycerin - 0.003, lidocaine - 0.1, tizol gel - up to 10 with the recommendation to lubricate the anal canal 3 times a day for 1 month.

At a rectal examination after 2 weeks: there is no sphincter spasm, with a digital examination, an anal fissure is not determined, there is no pain during the study, side effects are absent.

Example 6. Patient 23 years.

Complaints of pain in the anal canal during bowel movements, constipation, small amounts of blood in the stool. The duration of the disease is 5 months. Associates with the occurrence of constipation after childbirth six months ago. I independently applied candles with methyluracil, without a pronounced effect. The colon has not previously been examined.

On examination: satisfactory condition, normal nutrition, normal skin color, no enlarged lymph nodes, breathing is not difficult, pulse 78 per min - satisfactory properties, tongue is moist, stomach is soft, painless, liver is not palpated. Pasternatsky’s symptom is negative on the right and on the left.

Rectally: digital examination is sharply painful, the sphincter is spasmodic. A full study is not possible due to soreness. At 6 h, an anal fissure is determined, the edges are sealed.

Diagnosis: chronic posterior anal fissure, exacerbation.

Treatment was prescribed in the form of regulation of stool and local prescription of the drug composition, g: nitroglycerin - 0.02, lidocaine - 0.05, actovegin - 0.03, tizol gel - up to 10 with the recommendation to lubricate the anal canal 3 times a day for 1 month. For an additional therapeutic effect, a wound healing substance, Actovegin, was added to the composition.

During rectal examination after 2 weeks: there is no sphincter spasm, a finger examination revealed that the anal fissure is epithelized for 6 hours, there is no pain during the study, no side effects.

Example 7. Patient 45 years.

Complaints of periodically occurring pain in the anal canal during bowel movements, periodically blood in the feces. The duration of the disease is 3 years. I independently applied relif candles, candles with sea buckthorn oil, ointment proctosed, noted a short-term effect after courses of treatment. I turned to a coloproctologist a year ago, was prescribed medication using stool regulation, topical application of Actovegin gel, underwent rectoscopy. The effect of treatment is not noted.

On examination: satisfactory condition, increased nutrition, normal skin color, no enlarged lymph nodes, breathing is not difficult, pulse 72 min - satisfactory properties, tongue is moist, stomach is soft, painless, liver is not palpated. Pasternatsky’s symptom is negative on the right and on the left.

Rectally: digital examination is sharply painful, the sphincter is spasmodic. At 6 h, a dense anal fissure is determined, width 0.5 cm.

Diagnosis: chronic posterior anal fissure, exacerbation.

Treatment was prescribed in the form of regulation of stool and local administration of the drug composition, g: nifedepine - 0.01, lidocaine - 0.1, actovegin - 0.02, tizol gel - up to 10 with the recommendation to lubricate the anal canal 3 times a day for 1 month. For an additional therapeutic effect, a wound healing substance, Actovegin, was added to the composition.

When viewed after 2 weeks, complete epithelialization of the anal fissure was noted, side effects were absent.

The advantages of the claimed medicinal composition in comparison with the prototype (3) are as follows.

1. Achieving the effectiveness of treatment with a decrease in the concentration of active substances - nifedipine and nitroglycerin, which have significant contraindications and cause side effects.

2. Reducing the duration of treatment to 2-3 weeks by increasing the rate of penetration of the active substance into the area of the anal fissure.

3. The formation of a protective sterile film that protects the anal fissure from possible injuries.

4. The quickly achieved effect that improves the quality of human life - pain relief, lack of discomfort after 1-2 lubrications.

5. Complete cure in the absence of relapse.

6. No side effects.

7. Expanding the field of use of the medicinal composition for all types of anal fissures.

Claims (1)

A medicinal composition for the treatment of anal fissures, including a base, a drug that reduces spasms of smooth muscle, lidocaine, characterized in that the composition contains tizol gel as a base, and nifedipine or nitroglycerin as a drug that reduces spasms of smooth muscle in the following ratio of components , g:
cramping medication smooth muscle 0.003-0.02 lidocaine 0.05-0.1 tizol gel to 10