RU2657838C1 - Method of prophylaxis of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and is intended for the prevention of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy. Treatment is carried out, including Ursofalk, Mucofalk, and Chophytol. Take Ursofalk 10 mg/kg of body weight at night, Mucofalk – 1 sachet of 5 g 3 times a day for 15 minutes before meals, duration of admission both Ursofalk, and Mucofalk is 2 months after the surgery, then take Chophytol 2 tablets 3 times a day for a month. Course of prevention is repeated after 3 months.

EFFECT: method allows to reduce the incidence of fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy.

1 cl, 1 ex

Description

The invention relates to medicine, namely to internal medicine, in particular hepatology and gastroenterology, and can be used to prevent non-alcoholic fatty liver disease in patients with cholelithiasis (cholelithiasis) after laparoscopic cholecystectomy.

ZhKB is one of the most common pathologies of the digestive system. According to literature data [1, 2, 3], this disease is detected in 36-39% of patients with digestive pathology. The incidence of calculous cholecystitis is constantly growing - on average, twice for every 10 years. In recent years, a laparoscopic cholecystectomy has been universally recognized as the “gold” standard for surgical treatment of cholelithiasis. Only in the Russian Federation, up to 500,000 such operations are performed per year. But still, removal of the gallbladder does not eliminate the cholelithiasis itself, but often triggers a cascade of pathological processes leading to other functional and organic pathologies, combined by the term “postcholecystectomy syndrome”. According to various authors, up to 40% of patients undergoing cholecystectomy due to cholelithiasis suffer from it [1, 2, 3].

Non-alcoholic fatty liver disease is also an extremely common pathology. According to many authors, the incidence in Western Europe is 20-30%, and in Asia reaches 15% [4].

According to our own data, in 37% of patients by the end of 1 year after cholecystectomy according to liver ultrasound, signs of non-alcoholic fatty liver disease were first detected. However, these changes were not detected by ultrasound examination before the operation. It is especially important to note that these changes were detected even in those patients who did not complain before surgery - an asymptomatic course of cholelithiasis.

In the available literature, we have not found information on methods of preventing non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy, which, based on the above data, confirms the relevance of the development.

The technical result of the invention is the possibility of preventing non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy.

The technical result of the invention is achieved by the fact that they carry out a drug effect, including Ursofalk, Mukofalk and Hofitol. Ursofalk is taken at 10 mg / kg body weight at night, Mukofalk - 1 sachet of 5 g 3 times a day 15 minutes before meals, the duration of administration and Ursofalk and Mukofalk - 2 months after surgery, then take Hofitol 2 tablets 3 times a day for a month. The prophylaxis is repeated after 3 months.

The method is as follows:

Patients undergoing laparoscopic cholecystectomy for cholelithiasis are prescribed a treatment regimen: Ursofalk, Mukofalk and Hofitol. Ursofalk is taken at 10 mg / kg body weight at night, Mukofalk - 1 sachet of 5 g 3 times a day 15 minutes before meals. The duration of administration of both Ursofalk and Mukofalk is 2 months after the operation, then Hofitol is prescribed 2 tablets 3 times a day for a month. The prophylaxis is repeated after 3 months. For control purposes, all patients undergo examination: a biochemical analysis of blood and ultrasound of the abdominal organs, before surgery and 6 and 12 months after laparoscopic cholecystectomy.

The essential features of the proposed method and the causal relationship between them and the achieved technical result:

- Carry out a drug effect, including Ursofalk and Mukofalk, while Ursofalk take 10 mg / kg of body weight at night, Mukofalk - 1 sachet of 5 g 3 times a day 15 minutes before meals, the duration of administration and Ursofalk and Mukofalk - 2 months after surgery.

- Then take Hofitol 2 tablets 3 times a day for a month.

- The course of prevention is repeated after 3 months.

Numerous studies in recent years indicate that most patients with cholelithiasis have morphofunctional disorders in hepatocytes that underlie hepatic cell dyscholy, the formation of lithogenic bile, which determine the severity of biliary insufficiency and do not disappear after cholecystectomy (often the cause of changes in hepatocytes is cholestasis accompanying functional and organic disorders in cholelithiasis). From the point of view of pathophysiology, biliary insufficiency is characterized by a change in the qualitative composition and amount of bile produced. A qualitative change is based on the ratio between cholesterol and bile acids. The reason for the secretion of lithogenic bile, the development of biliary insufficiency and, as a result, digestive disorders is the decrease in the activity of the enzyme cholesterol7α-hydroxylase, which converts cholesterol into bile acids. Due to the loss of the concentration function of the gallbladder after cholecystectomy, choleresis increases in most patients, the severity of biliary insufficiency increases, which reflexively accelerates the enterohepatic circulation of bile acids. In turn, this phenomenon inhibits the synthesis of bile acids in the body, thereby exacerbating biliary insufficiency [5, 6, 7].

It is important to note that lipid metabolism also affects the lithogenic properties of bile. With a violation of the synthesis of cholesterol and bile acids, as well as with cholestasis, an accumulation of cholesterol occurs, which leads to damage to hepatocytes. These phenomena cause morphological and functional changes in the liver parenchyma, often in the form of non-alcoholic fatty liver disease or steatohepatitis [5, 6, 7].

Given the above pathogenetic mechanisms of the occurrence and progression of both cholelithiasis and non-alcoholic fatty liver disease, the basis for choosing the components that we developed the prevention scheme was:

Ursofalk is one of the key agents in the treatment of not only pathological conditions that occur after cholecystectomy, but also the cholelithiasis itself, affecting the basic pathogenetic mechanisms of stone formation.

Cholelitholytic and hypocholesterol action: reduces the synthesis of cholesterol by the liver, its absorption in the intestine, its content in bile, forms liquid crystals with it, mobilizes cholesterol from stones, thereby partially or completely dissolving cholesterol stones.

Choleretic effect: by increasing the concentration of hydrophilic ursodeoxycholic acid (UDCA), it reduces the amount of toxic hydrophobic FAs in bile, increases their excretion into the small intestine and reduces their absorption in the ileum.

Hepatoprotective effect: UDCA has the ability to integrate into the lipid layer of the hepatocyte cell membrane, thereby stabilizing and increasing its protective properties, which can inhibit the development and progression of non-alcoholic fatty liver disease.

Immunomodulating effect: reduces the expression of certain antigens on the hepatocyte membrane, affects the number of T-lymphocytes, eosinophils and some pro-inflammatory cytokines, preventing damage to hepatocytes [8, 9].

Information on the use of Ursofalk as monotherapy, as well as in combination with other drugs for the prevention of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy, was not found.

URSOFALK (Ursofalk) - instructions for use Registration number:

P N014714 / 02-050309

Brand Name: URSOFALK

International Nonproprietary Name:

Ursodeoxycholic acid.

Dosage forms: capsules, suspension

Structure

Capsules: One capsule contains 250 mg of ursodeoxycholic acid. Excipients: corn starch, colloidal silicon dioxide, magnesium stearate, titanium dioxide, gelatin, purified water, sodium lauryl sulfate. Suspension: 5 ml of suspension (1 scoop) contain 250 mg of ursodeoxycholic acid.

Excipients: benzoic acid, purified water, xylitol, glycerol, microcrystalline cellulose, propylene glycol, sodium citrate, sodium cyclamate, anhydrous citric acid, sodium chloride, lemon flavor (GivaudanPHL-134488).

Description

Capsules: Hard, opaque gelatin capsules No. 0; white cap, white body. The contents of the capsule are white powder or granules.

Suspension: A homogeneous white suspension containing small air bubbles with a lemon flavor.

Pharmacotherapeutic group

Hepatoprotective agent.

ATX Code: A05AA02

Pharmacological properties

Hepatoprotective agent, has a choleretic effect. Reduces the synthesis of cholesterol in the liver, its absorption in the intestine and concentration in bile, increases the solubility of cholesterol in the biliary system, stimulates the formation and secretion of bile. Reduces the lithogenicity of bile, increases the content of bile acids in it; causes increased gastric and pancreatic secretion, enhances lipase activity, has a hypoglycemic effect. Causes partial or complete dissolution of cholesterol stones during enteral use, reduces the saturation of bile with cholesterol, which helps mobilize cholesterol from gallstones. It has an immunomodulatory effect, affects the immunological reactions in the liver: it reduces the expression of certain antigens on the hepatocyte membrane, affects the number of T-lymphocytes, the formation of interleukin-2, and reduces the number of eosinophils [8].

Indications for use

The drug is used for diseases of the liver and gall bladder, which are accompanied by cholestasis, an increase in blood cholesterol and a decrease in certain liver functions, including:

- primary biliary cirrhosis, biliary reflux esophagitis and reflux gastritis;

- primary sclerosing cholangitis;

- hepatitis of various etiologies, including acute hepatitis, chronic active hepatitis and chronic hepatitis, which are accompanied by cholestasis;

- cholesterol stones in the gall bladder, and the drug is recommended to be used only if the size of the stones does not exceed 15 mm in diameter, the stones are X-ray negative and the gall bladder function is not impaired in patients.

- Cystic fibrosis;

- toxic liver damage, including in acute and chronic alcohol poisoning;

- diseases of the liver with cholestasis in children, atresia of the intrahepatic bile ducts;

- biliary dyskinesia;

- the drug is taken to eliminate stagnation of bile in patients who are on parenteral nutrition, as well as in patients who underwent surgery for liver transplantation;

- the drug is also prescribed for the prevention of liver damage when taking medications, including drugs with a cholestatic effect and hormonal contraceptives;

- for the prevention of colon cancer in patients at risk [9].

Contraindications

X-ray positive (high calcium) gallstones; non-functioning gall bladder; acute inflammatory diseases of the gallbladder, bile ducts and intestines; decompensated liver cirrhosis; severe impaired renal, liver, pancreas; hypersensitivity to the components of the drug. Ursodeoxycholic acid has no age restrictions in use, but for children under 3 years of age, it is recommended to use Ursofalk in suspension, as it may be difficult to swallow capsules.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Children and adults with body weight less than 34 kg are recommended to use Ursofalk in suspension.

Dissolution of cholesterol gallstones

The recommended dose is 10 mg of ursodeoxycholic acid per 1 kg of body weight per day, which corresponds to

250 mg capsules

Suspension for oral administration

The drug must be taken daily in the evening, before bedtime (capsules do not chew), washed down with a small amount of liquid. The duration of treatment is 6-12 months. For the prevention of re-cholelithiasis, the drug is recommended for several months after the dissolution of the stones.

Treatment of biliary reflux gastritis

1 capsule (1 scoop) Ursofalk daily in the evening before bedtime with a little water. The course of treatment is from 10-14 days to 6 months, if necessary - up to 2 years.

Symptomatic treatment of primary biliary cirrhosis

The daily dose depends on body weight and ranges from 2 to 6 capsules (scoops) (from about 10 to 15 mg of ursodeoxycholic acid per 1 kg of body weight).

The following application regimen is recommended:

250 mg capsules

Suspension for oral administration

Side effects

Diarrhea, nausea, pain in the epigastric region and right hypochondrium, calcification of gallstones, increased activity of “liver” transaminases, allergic reactions.

In the treatment of primary biliary cirrhosis, transient decompensation of cirrhosis of the liver may occur, which disappears after discontinuation of the drug.

Overdose

No cases of overdose have been identified. In case of an overdose, symptomatic treatment is performed.

Interaction with other drugs

Colestyramine, colestipol and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce the absorption of ursodeoxycholic acid in the intestine and thus reduce its absorption and effectiveness. If the use of drugs containing at least one of these substances is nevertheless necessary, they must be taken at least 2 hours before taking Ursofalk.

Ursodeoxycholic acid can enhance the absorption of cyclosporin from the intestine. Therefore, in patients taking cyclosporine, the doctor should check the concentration of cyclosporin in the blood and adjust the dose of cyclosporine if necessary.

In some cases, Ursofalk may decrease the absorption of ciprofloxacin. Hypolipidemic drugs (especially clofibrate), estrogens, neomycin, or progestins increase bile saturation with cholesterol and may decrease the ability to dissolve cholesterol bile calculi.

special instructions

In cholelithiasis, the effectiveness of treatment is monitored every 6 months by X-ray and ultrasound examination of the biliary tract in order to prevent relapse of cholelithiasis. In cholestatic liver diseases, serum transaminases, alkaline phosphatases and gamma-glutamyl transpeptidases should be periodically determined.

Release form

Capsules 250 mg, 10 capsules in aluminum / PVC blister; 1 blister together with instructions for use in a cardboard pack. Capsules 250 mg, 25 capsules per aluminum / PVC blister; 2 and 4 blisters along with instructions for use in a cardboard pack.

Suspension for oral administration 250 mg / 5 ml, 250 ml each in a dark glass vial with a screw cap with a first opening control; 1 bottle together with a measuring spoon and instructions for use in a cardboard pack.

Storage conditions

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life

Capsules - 5 years. Suspension - 4 years. After opening, 4 months.

Do not use after the expiration date indicated on the package.

Pharmacy Vacation Terms

Prescription [8]

Mucofalk is the only registered drug based on plant fiber. It creates the conditions for physiological functioning of the normal microflora of the colon and promotes the regeneration of damaged cells of the intestinal epithelium. After cholecystectomy, it is extremely important to ensure regular adequate bowel movement. Pathological conditions that occur after surgery are often associated with defective digestion, antibiotic therapy, or the permanent entry of bile into the small intestine. In this regard, the relevance of the use of Mukofalk is very high. It is a universal drug related to stool regulators (both with diarrhea and constipation) [10]. In addition, Radchenko V.G., Seliverstov P.V. and Sitkin S.I. proved the litholytic effect of this drug in the first stage of cholelithiasis (RU 2519198, 2014), which actualizes the use of Mukofalk as a drug that prevents the formation of biliary sludge in the biliary tract after cholecystectomy. In addition, when using Mukofalk in case of mild to moderate hypercholesterolemia, there is a decrease in LDL cholesterol by about 7%.

Information on the use of Mukofalk as monotherapy, as well as in combination with other drugs for the prevention of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy, was not found.

It is known that the simultaneous use of Ursofalk and Mukofalk enhances the expected therapeutic effect in the treatment of non-alcoholic steatohepatitis (one of the forms of non-alcoholic fatty liver disease) [11].

Information on the simultaneous use of Ursofalk and Mukofalk for the prevention of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy was not found.

Due to the fact that overweight, hypercholesterolemia and insulin resistance are risk factors for the development of non-alcoholic fatty liver disease, in the scheme we developed, Mukofalk is taken 15 minutes before a meal [12].

MUKOFALK (Mucofalk®) - instructions for use

Registration number: P N014176 / 01 of 07.14.2008

Trade Name: Mucofalk

International non-proprietary or group name:

Plantain Oval Seed Shell

Dosage form: Orange granules for oral suspension

Structure

5 g of granules (1 sachet or 1 scoop) contains:

Active ingredient: Oval plantain seed shell powder (Plantago ovata Forssk.) - 3.25 g

Excipients: sucrose 0.4795 g, citric acid 0.4350 g, dextrin 0.2940 g, sodium alginate 0.2515 g, sodium citrate 0.2250 g, sodium chloride 0.0150 g, sodium saccharinate 0.0100 g, orange flavor 0,0400 g. 5 g of granules contains the amount of digestible carbohydrates corresponding to 0,064 bread units.

Description

Light brown granules with inclusions from brown particles of the peel and adjacent cells of the shell of dried oval plantain seeds (Plantago ovata Forssk).

Pharmacotherapeutic group

Herbal Laxative

ATX Code: A06AC01

Pharmacological properties

Pharmacodynamics

The active ingredient in plantain seed coatings consists of an episperm and adjacent layers of dried mature plantain seeds of the oval Plantago ovata Forssk. (Plantago ispaghula Roxb.). Plantain seed coatings are especially rich in dietary fiber and plant mucus; their content is much higher than other types of plantain. Plantain seed shells are capable of absorbing a volume of water up to 40 times their own mass. They are 85% composed of water-soluble fiber, which is partially amenable to fermentation (in vitro the non-fermentable residue is 72%) and promotes stool hydration. Intestinal motility and the rate of passage of its contents may vary under the influence of plantain seed coat by mechanical expansion of the intestinal wall. This occurs as a result of an increase in the mass of the contents of the colon and a decrease in its viscosity due to absorption of water. When taking shells of plantain seeds with a large amount of liquid, the volume of intestinal contents increases due to its high volume-forming ability, as a result, the stretching of the anal sphincter is stimulated, which causes defecation. At the same time, the swollen mass of the mucous substance forms a lubricating layer, which facilitates the passage of intestinal contents. The drug restores normal bowel function. Onset: Plantain seed coat usually acts as a laxative within 12-24 hours after a single dose. Sometimes the maximum effect is achieved only after 2-3 days.

With mild to moderate hypercholesterolemia, there was a decrease in LDL cholesterol by about 7%. Studies of the effect of plantain seed coat on the frequency of cardiovascular complications and overall mortality have not been conducted.

Indications for use

Constipation, anal fissures, hemorrhoids, the postoperative period during interventions in the anorectal region (in order to create a softer consistency in the stool), functional diarrhea, irritable bowel syndrome, as an adjunct to the diet for hypercholesterolemia.

Contraindications

Hypersensitivity to psyllium (psyllium psyllium) or any component of the drug, any sudden changes in bowel movements that persist for more than 2 weeks, undiagnosed rectal bleeding, inability to defecate after using a laxative, difficulty swallowing, and other problems throat and pharynx, stenosis of the esophagus, cardia or gastrointestinal tract, potential or existing intestinal obstruction (ileus), intestinal paralysis or megacolo syndrome hereditary fructose intolerance, glucose-galactose malabsorption or congenital insufficiency of sucrose-isomaltase, children under 12 years old.

Carefully

Coprostasis or symptoms such as abdominal pain, nausea and vomiting, which may be a sign of potential or existing intestinal obstruction.

Use during pregnancy and during breastfeeding

There are no contraindications to taking the drug during pregnancy and lactation. There is limited evidence (less than 300 pregnancies) regarding the use of the drug during pregnancy. Data from animal studies to determine reproductive toxicity are limited. The use of this drug during pregnancy and during breastfeeding can be considered if necessary and if measures to change the diet have not brought positive results.

Bulk-forming laxatives should be used before using other laxatives.

Dosage and administration

For oral administration.

For the treatment of chronic constipation and conditions in which a soft stool is required (for example, in the presence of anal fissures, hemorrhoids): Adults and adolescents over 12 years old - 1 sachet or 1 scoop of Mukofalk 2-3 times a day after stirring in large quantities liquids (not less than 150 ml).

As maintenance therapy in patients with functional diarrhea, irritable bowel syndrome or hypercholesterolemia:

Adults and adolescents over 12 years of age with 1 sachet or 1 scoop of Mukofalk 2-6 times a day after stirring in a large amount of liquid (at least 150 ml).

With elevated cholesterol (mild to moderate), it is recommended to take Mukofalk with food. Mucofalk should be mixed with a sufficient amount of water, fruit juice or similar liquids (at least 150 ml). After mixing, the resulting suspension must be taken as soon as possible. Following this, you should drink an additional amount of liquid (one glass) (see the section "Special Instructions").

Mucofalk should not be taken lying down or immediately before bedtime. Mucofalk should be taken during the day, at least 30-60 minutes before taking other drugs or 30-60 minutes after taking them (see section "Interaction with other drugs").

If the patient has prolonged constipation and irregular stool for more than 3 days, or diarrhea that lasts more than 2 days or is accompanied by blood or fever, you should consult a doctor.

Children

The experience of treating Mukofalk with children under 12 years of age is limited, therefore, children under 12 years of age are not recommended to use the drug.

The drug should be stored in its original packaging to protect the contents from moisture. After opening the jar with the drug, it must be tightly closed.

Side effect

May increase flatulence and the appearance of a feeling of fullness in the abdomen, however, in the process of further treatment, these phenomena, as a rule, pass. Bloating and coprostasis may develop. There is also a risk of developing ileus or obstruction of the esophagus, especially when taking the drug without enough fluid. Plantain seed coat contains allergens that can lead to hypersensitivity reactions when taken orally or in contact with skin. Possible symptoms of a hypersensitivity reaction include rhinitis, conjunctivitis, bronchospasm, and in some cases, anaphylactic shock. Skin reactions such as exanthema and pruritus have also been noted. The frequency of these adverse effects is unknown. If any of the side effects indicated in the instructions are aggravated, or you notice other side effects not listed in the instructions, please inform your doctor.

Overdose

An overdose of Mukofalk can cause discomfort in the abdomen, flatulence and lead to the development of intestinal obstruction. It is necessary to use a sufficient amount of liquid, the treatment of overdose symptoms is symptomatic.

Interaction with other drugs

When the drug is used together with such drugs as minerals, vitamins (vitamin B12), cardiac glycosides, coumarin derivatives, carbamazepine and lithium preparations, their absorption in the small intestine can slow down. For this reason, Mukofalk should be taken 30-60 minutes before taking other medicines or 30-60 minutes after taking them.

In order to reduce the risk of obstruction, treatment with Mukofalk when taken together with drugs that inhibit intestinal motility (such as opiates, loperamide) should be carried out under medical supervision.

Separate studies have shown that plantain seed coat cause a decrease in blood glucose. Patients with diabetes receiving treatment with Mukofalk may need a dose adjustment of antidiabetic drugs. It is impossible to exclude the possibility of weakening the action of thyroid hormones, even if their intake is not carried out simultaneously with the intake of Mukofalk.

special instructions

When taking the drug should drink at least 1.5 liters of fluid per day. The use of plantain seed coatings as an aid to the diet for hypercholesterolemia requires medical supervision.

In the absence of a doctor's prescription:

Mucofalk should not be taken in patients with coprostasis and symptoms such as abdominal pain, nausea, and vomiting. These symptoms may be signs of potential or existing intestinal obstruction. Patients taking Mukofalk for the treatment of chronic constipation should stop treatment with Mukofalk and consult a doctor if they experience abdominal pain or have irregular stools. During the intake of Mukofalk, it is necessary to ensure an abundant intake of liquid, for example, 150 ml of water (1 cup of water) for each sachet / measuring spoon (equivalent to 5 g) of Mukofalk. Ingestion of dry granules can cause difficulty in swallowing and suffocation. In the absence of an adequate amount of fluid, the use of volume-forming drugs can lead to obstruction of the respiratory tract and esophagus, accompanied by suffocation and intestinal obstruction. Symptoms of these phenomena may include chest pain, vomiting, or difficulty swallowing or breathing. Treatment of debilitated patients and / or elderly patients requires medical supervision. In the presence of gastrointestinal diseases, the most important aspect of treatment is the replacement of fluids and salts (electrolytes).

Mucofalk contains sucrose.

Patients with hereditary fructose intolerance, glucose-galactose malabsorption, or congenital sucrose-isomaltase deficiency should avoid the use of sucrose.

A single dose of Mukofalk (5 g) contains 0.5 g of sucrose and 3.07 kcal (12.86 kJ), which is equivalent to 0.064 bread units. A single dose of Mukofalk (5 g) contains 3.9 mmol (90 mg) of sodium. This should be considered for individuals on a controlled sodium diet (low in sodium / sodium chloride).

Influence on the ability to drive vehicles, mechanisms

The use of the drug does not affect the ability to carry out potentially dangerous types of activities that require increased concentration of attention and speed of psychomotor reactions (including driving vehicles, working with moving mechanisms).

Release form

Orange granules for suspension for oral administration.

1. 5 g per bag of laminated material paper / polyethylene / aluminum / polyethylene. 20 sachets together with instructions for use in a cardboard box.

2. 150 g or 300 g each in a jar of multilayer paper, coated on the inside with aluminum foil, on the outside - a laminated layer with a label, the bottom is metal with a galvanized coating. The can is sealed with aluminum foil and closed with a polyethylene lid. A measuring spoon is embedded inside the can. Instructions for use nested between aluminum foil and cover. Each jar is placed in a pack of cardboard.

Storage conditions

Store in a dry place at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life

For sachets - 5 years. For cans - 3 years. After opening the package, use within 6 months. The drug should not be used after the expiration date indicated on the package.

Holiday Terms

They are released without a prescription [13].

Hofitol is a drug that stimulates the secretion of bile due to the production of bile acids and organic anions. It has a slight stimulating effect and is relevant for biliary insufficiency. The drug increases the ability of hepatocytes to produce coenzymes, which improves the metabolism of cholesterol and lipids. In addition, the drug has a hepatoprotective and lipid-lowering effect [14].

Information on the use of Hofitol as monotherapy, as well as in combination with other drugs for the prevention of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy, was not found.

The consistent appointment of Ursofalk and Hofitol is dictated by the fact that both drugs have a choleretic effect and their simultaneous administration is not advisable.

HOFITOL (tablets) - instructions for use.

(Chophytol)

Registration number: P N013320 / 01

Brand Name: HOPHITOL (CHOPHYTOL)

Dosage form: coated tablets

Composition (per 1 tablet)

The core of the tablet:

Active component:

Artichoke Field (Cynara scolymus L.) leaf extract dry (aqueous) 200 mg (0.20 g)

Excipients:

Magnesium trisilicate 12.00 mg, Corn starch 22.00 mg, Talc 3.00 mg, Magnesium stearate 3.00 mg.

Shell tablets:

Gummilak 1.1520 mg, Rosin 1.1520 mg, Talcum 16.300 mg, Gelatin 0.384 mg, Sucrose 86.146 mg, Calcium carbonate 2.2 mg, Dispersed colorant * 2.580 mg, Carnauba wax 0.082 mg, Polysorbate 80 0.004 mg.

The composition of the dispersed dye is sucrose, yellow, black, and brown iron oxides (E 172), methyl parahydroxybenzoate (E 218), and ethyl parahydroxybenzoate (E 214).

Description

Round biconvex tablets, coated with a brown coating.

Pharmacotherapeutic group

Cholagogue means of plant origin.

ATX Code: A05AX

Pharmacological properties

The pharmacological effect of the drug is due to a complex of field biologically active substances that make up the leaves of the artichoke. Cinarin in combination with phenolic acids has a choleretic, as well as hepatoprotective effect. Ascorbic acid, carotene, vitamins B1 and B2, inulin contribute to the normalization of metabolic processes. It also has a diuretic effect and enhances urea excretion.

Indications for use

The drug is used in the complex treatment of biliary dyskinesia according to the hypokinetic type, chronic non-calculous cholecystitis, chronic hepatitis, cirrhosis; chronic nephritis, chronic renal failure.

Contraindications

Hypersensitivity to the components of the drug, gallstone disease, obstruction of the biliary tract, acute diseases of the liver, kidneys, bile and urinary tract.

Children under 6 years old.

Use during pregnancy and lactation

The use of Hofitol during pregnancy and lactation is possible only as directed and under the supervision of a physician.

Dosage and administration

Inside. Adults take 2-3 tablets 3 times daily before meals.

Children over 6 years old are recommended to take 1-2 tablets (depending on age) 3 times a day before meals.

The course of treatment is 2-3 weeks.

Repeated courses of treatment are possible in consultation with the doctor.

Side effects

Allergic reactions are possible, with prolonged use of the drug in high doses, diarrhea may develop.

Release form

Coated tablets.

12 tablets in a blister pack ((PVC - aluminum), (PVC / PVDC / PE-aluminum)), five blisters are placed in a cardboard box along with instructions for use.

30 tablets in a blister pack ((PVC - aluminum), (PVC / PVDC / PE-aluminum)), two blisters are placed in a cardboard box along with instructions for use.

30 tablets in a blister pack ((PVC - aluminum), (PVC / PVDC / PE-aluminum)), six blisters are placed in a cardboard box along with instructions for use.

For 60 and 180 tablets in a polypropylene tube, closed with a polyethylene lid, with instructions for use in a cardboard box.

Storage conditions

At a temperature of no higher than 25 ° C out of the reach of children.

Shelf life

3 years.

Do not use after the expiration date indicated on the package.

Pharmacy Vacation Terms

Over the counter [15].

The duration of taking Ursofalk, Mukofalk and Hofitol, as well as the time of repeated passage of the course of prevention developed by us, is justified by our own clinical data obtained by testing the proposed method.

We give clinical examples:

Example 1 (testing of the proposed method).

Patient N., 38 years old, male sex., Height - 170 cm, weight - 90 kg, BMI - 31.

Diagnosis: cholelithiasis. Chronic calculous cholecystitis.

A patient on March 25, 2015, in a surgical clinic, had a planned laparoscopic cholecystectomy for cholelithiasis.

Before the operation, the patient was worried about complaints: periodic discomfort in the right hypochondrium after eating, bitterness in the mouth after a plentiful and fatty meal, constipation.

Objectively: The condition is satisfactory, the consciousness is clear. AD-130/70 mm RT. st .; Pulse - 78 per minute, rhythm .; the abdomen is soft, sensitive to palpation in the right hypochondrium. The chair is decorated with a tendency to constipation, the usual color.

According to the ultrasound of the hepatobiliary system before surgery:

The liver is not enlarged / CWR - 145 mm, the left lobe is 52 × 72 mm /. Physiological mobility is preserved in full. The echogenicity of the liver is normal, the contour is even, the echostructure is fine-grained, homogeneous, the intrahepatic ducts are not dilated, the foci are not determined, the vascular pattern is not changed.

The portal vein is not expanded by 9 mm.

Gall bladder: regular shape, not enlarged 60 × 24 mm, the wall is flat, not thickened, acoustically sealed. The contents are anechoic, with one movable calculus of 20 mm with a clear acoustic shadow.

The common bile duct is not expanded, 4 mm in d, is free on the visible fragment.

Conclusion: cholelithiasis, calculous cholecystitis.

According to biochemical analysis of blood before surgery:

Bilirubin - 21 μmol / l; ALT-30 U / L; AST-22 U / L; Total cholesterol - 6.1 mmol / l.

Treatment:

After surgical treatment and the end of the period of surgical inpatient observation, the patient was assigned to the outpatient stage: Ursofalk at 10 mg / kg body weight (4 capsules) at night, Mukofalk - 1 sachet of 5 g 3 times a day 15 minutes before meals, duration of admission and Ursofalk and Mukofalka - 2 months. Then Hofitol was prescribed 2 tablets 3 times a day for a month.

The prophylaxis was repeated after 3 months.

Control turnout No. 1 for examination (6 months after surgery) was scheduled for September 28, 2015:

Complaints: Actively does not show. He took the prescribed drugs in accordance with the prescriptions.

Objectively: Weight - 87 kg. BMI - 30. Satisfactory condition, clear consciousness. HELL - 125/80 mm RT. st .; Pulse - 70 per minute, rhythm .; the abdomen is soft, painless. The chair is decorated, regular, regular color.

According to the ultrasound of the hepatobiliary system from 09/28/2015 g (6 months after surgery):

The liver is not enlarged / CWR - 145 mm, the left lobe - 53 × 71 mm /. Physiological mobility is preserved in full. The echogenicity of the liver is normal, the contour is even, the echostructure is fine-grained, homogeneous, the intrahepatic ducts are not dilated, the foci are not determined, the vascular pattern is not changed. No negative dynamics from a previous study.

The portal vein is not expanded 10 mm.

Gall bladder: removed. The gallbladder bed in the form of a site of increased echogenicity without additional formations.

The common bile duct is not expanded, 6 mm in d, is free on the visible fragment.

Conclusion: condition after cholecystectomy;

According to a biochemical blood test:

Bilirubin - 17 μmol / l; ALT-36 U / L; AST-32 U / L; Total cholesterol - 5.7 mmol / l.

Control turnout No. 2 for examination (12 months after surgery - completion of observation) was scheduled for 03/29/2016:

Complaints: Actively does not show. He took the prescribed drugs in accordance with the prescriptions.

Objectively: Weight - 85 kg. BMI - 29. Satisfactory condition, clear consciousness. HELL - 135/90 mm RT. st .; Pulse - 74 per minute, rhythm .; the abdomen is soft, painless. The chair is decorated, regular, regular color.

According to the ultrasound of the hepatobiliary system 03/29/2016, (12 months after surgery):

The liver is not enlarged / CWR - 145 mm, the left lobe is 52 × 73 mm /. Physiological mobility is preserved in full. The echogenicity of the liver is normal, the contour is even, the echostructure is fine-grained, homogeneous, the intrahepatic ducts are not dilated, the foci are not determined, the vascular pattern is not changed. No negative dynamics from a previous study.

The portal vein is not expanded 10 mm.

Gall bladder: removed. The gallbladder bed in the form of a site of increased echogenicity without additional formations.

The common bile duct is not expanded, 7 mm in d, is free on the visible fragment.

Conclusion: condition after cholecystectomy;

According to a biochemical blood test:

Bilirubin - 14 μmol / l; ALT - 28 units / l; ACT - 24 U / L; Total cholesterol - 5.0 mmol / L.

Conclusion: In the patient, on the background of taking the prophylaxis regimen we claimed for the first year after the operation, according to ultrasound, there were no signs of the development of non-alcoholic liver disease.

Example 2 (control group).

Patient J., 40 years old, male sex., Height - 173 cm, weight - 88 kg, BMI - 29.

Diagnosis: cholelithiasis. Chronic calculous cholecystitis.

A patient had a laparoscopic cholecystectomy for cholelithiasis in a surgical clinic on 12.11.2014.

Before the operation, the patient was worried about complaints: pain in the right hypochondrium after eating fatty foods, periodically nausea, a tendency to constipation.

Objectively: The condition is satisfactory, the consciousness is clear. AD-115/75 mmHg st .; Pulse - 72 per minute, rhythm .; the abdomen is soft, sensitive to palpation in the right hypochondrium and the point of the gallbladder. The chair is decorated with a tendency to constipation, the usual color.

According to the ultrasound of the hepatobiliary system before surgery:

The liver is not enlarged / CWR - 146 mm, the left lobe - 57 × 75 mm /. Physiological mobility is preserved in full. The echogenicity of the liver is normal, the contour is even, the echostructure is fine-grained, homogeneous, the intrahepatic ducts are not dilated, the foci are not determined, the vascular pattern is not changed. The portal vein is not expanded 12 mm.

Gall bladder: regular shape, not enlarged 70 × 23 mm, the wall is flat, not thickened, acoustically sealed. The content is anechoic, with two visible moving stones 8 mm and 15 mm with a clear acoustic shadow.

The common bile duct is not expanded, 5 mm in d, is free on the visible fragment.

Conclusion: cholelithiasis, calculous cholecystitis - 2 calculi 8 mm and 15 mm;

According to biochemical analysis of blood before surgery:

Bilirubin - 18 μmol / l; ALT-37 U / L; AST-35 U / L; Total cholesterol - 5.8 mmol / L.

Treatment:

After surgical treatment and the end of the period of surgical inpatient observation, the patient was not prescribed mandatory drugs for outpatient treatment. The condition was introduced that when complaints or discomfort associated with something appeared, the patient would appear at an unplanned appointment to prescribe symptomatic therapy.

Control turnout No. 1 for examination (6 months after surgery) was scheduled for 05/15/2015:

Complaints: For the period between visits, I did not seek medical help, I did not take any medications myself. Over the past 1.5 months, periodically, with errors in the diet, he noted severity in the right hypochondrium.

Objectively: Weight - 90 kg. BMI - 30. Satisfactory condition, clear consciousness. HELL - 130/80 mm RT. st .; Pulse - 77 per minute, rhythm .; the abdomen is soft, painless. The chair is decorated, regular, regular color.

According to the ultrasound of the hepatobiliary system 05/15/2015 g (6 months after surgery):

The liver is enlarged / CWR - 155 mm, the left lobe is 70 × 87 mm /. Physiological mobility is preserved in full. The contours are even, fuzzy, preserved. The pattern of intrahepatic structures is poorly differentiated. The echogenicity of the liver is slightly increased, the echostructure is fine-grained, not homogeneous, the intrahepatic ducts are not dilated, the foci are not determined, the vascular pattern is somewhat depleted on the periphery.

The portal vein is not expanded 12 mm.

Gall bladder: removed. The gallbladder bed in the form of a site of increased echogenicity without additional formations.

The common bile duct is not expanded, 8 mm in d, is free on the visible fragment.

Conclusion: condition after cholecystectomy; signs of liver steatosis.

According to a biochemical blood test:

Bilirubin - 20 μmol / L; ALT- 41 U / L; AST-37 U / L; Total cholesterol - 5.7 mmol / l.

Symptomatic therapy is recommended for the patient: Tab. Duspatalin 200 mg 2 times a day for a week.

The patient did not come to an unscheduled follow-up appointment, citing by phone that he was no longer bothered by anything. According to the words, the recommended drug was not taken.

Control turnout No. 2 for examination (12 months after surgery - completion of observation) was scheduled for 11/16/2015:

Complaints: Periodically, bitterness in the mouth and heaviness in the right hypochondrium during the intake of fatty foods.

Objectively: Weight - 89 kg. BMI - 30. Satisfactory condition, clear consciousness. HELL - 120/80 mm RT. st .; Pulse - 70 per minute, rhythm .; the abdomen is soft, painless. The chair is decorated, regular, regular color.

According to the ultrasound of the hepatobiliary system November 16, 2015 g (12 months after surgery):

The liver shows an increase in the size of the organ lobes / CWR - 160 mm, the left lobe - 83 × 96 mm /. Physiological mobility is preserved in full. The contours are even, fuzzy, preserved. The pattern of intrahepatic structures is poorly differentiated. The parenchyma is veiled, with a diffuse increase in echogenicity, most pronounced in the right lobe. The pattern of intrahepatic ducts is practically not traced. The visualized fragments of the intrahepatic vessels are not dilated, their walls are slightly thickened in some areas, with a moderate increase in echogenicity. Reliable echoes of organized structures in the liver and perihepatic spaces are not detected.

The portal vein is not expanded 11 mm.

Gall bladder: removed. The gallbladder bed in the form of a site of increased echogenicity without additional formations.

The common bile duct is not expanded, 8 mm in d, is free on the visible fragment

Conclusion: condition after cholecystectomy; signs of liver steatosis.

According to a biochemical blood test:

Bilirubin - 17 μmol / L; ALT- 36 U / L; ACT- 29 U / L; Total cholesterol - 6.0 mmol / L.

Conclusion: according to ultrasound, the patient showed signs of non-alcoholic fatty liver disease in the first year after the operation, with their initial absence according to ultrasound before the operation.

Using the proposed method, we examined 60 patients aged 38 ± 10.3 years (women 60%, men 40%) who underwent planned laparoscopic cholecystectomy for cholelithiasis in 2014-2015. According to ultrasound, all patients did not detect signs of non-alcoholic fatty liver disease before surgery. The follow-up period was 1 year. Patients were divided into 2 groups of 30 people. Group 1 included patients who tested the inventive method. Group 2 included patients who received symptomatic therapy “on demand”: antispasmodics (including No-shpa and Duspatalin), enzyme preparations (including Creon). Both groups before the start of the observation period received the same recommendations about the need for diet, weight loss and physical activity. All patients underwent examination: a biochemical analysis of blood and ultrasound of the abdominal cavity organs, before surgery and 6 and 12 months after laparoscopic cholecystectomy.

Of the 60 patients included in the study, 13 (21.6%) people by the end of 1 year after cholecystectomy according to liver ultrasound revealed the first signs of non-alcoholic fatty liver disease. In the 1st group of patients, by the end of the 1st year after laparoscopic cholecystectomy, signs of non-alcoholic fatty liver disease were detected in 2 (6.6%) people. A decrease in body weight in patients of the 1st group was observed in 21 (70%) patients by an average of 3.3 ± 1.3 kg per year of observation. Cholesterol level decreased to 5.348 ± 0.077 mmol / L (p <0.05). In group 2, ultrasound signs of non-alcoholic fatty liver disease appeared in 11 (36.6%) patients. A decrease in body weight was observed in 6 (20%) people by an average of 2.1 ± 0.78 kg per year. No significant reduction in cholesterol was observed.

From which it can be concluded that in the group of patients in which the claimed method of prevention was not applied, the incidence of non-alcoholic fatty liver disease was 6 times higher.

Thus, a method for the prevention of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy was first developed.

Literature

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Claims (1)

A method for the prevention of non-alcoholic fatty liver disease in patients with cholelithiasis after laparoscopic cholecystectomy, which consists in a drug effect, including Ursofalk, Mukofalk and Hofitol, with Ursofalk taking 10 mg / kg body weight at night, Mukofalk - 1 sachet of 5 g 3 times per day 15 minutes before meals, the duration of administration of both Ursofalk and Mukofalk is 2 months after the operation, then Hofitol is taken 2 tablets 3 times a day for a month, the prophylaxis is repeated after 3 months.