ACID-MINERAL COMPOSITION FOR AN ENTERAL SOLUTION

Abstract

The invention is used in conducting intestinal lavage and enteral correction of body homeostasis disorders, shortening a regeneration period of the mucosa of the gastrointestinal tract (GIT), reducing a rate of extraintestinal complications related to hyperpermeability of the intestinal barrier, and preventing edemas after intestinal lavage at various diseases. The invention includes an acid-mineral composition (AMC) and a solution of sodium phosphate mono-, or twice-, or triple-substituted, or potassium phosphate mono- or twice-substituted, sodium chloride, sodium acetate, potassium chloride, calcium chloride, magnesium sulphate, citric acid, and water. The osmolarity of the solution is preferably in the range from 280 to 310 mOsm/L. The invention may further comprise aminopolycarboxylic acids and short-chain carboxylic (fatty) acids to provide a solution pH from 4.61 to 5.8.

Claims

1. An acid-mineral composition for producing an enteral solution for a lavage of a gastrointestinal tract and/or a correction of homeostasis disorders, comprising: a mixture of salts of sodium, potassium, calcium, and magnesium, each of which are taken in quantities providing mineralization of the enteral solution in a range from 10.7 g to 14.0 g per 1 L of the enteral solution; aminopolycarboxylic acids or their sodium salts in a quantity preventing insoluble salts of calcium and magnesium from forming in the enteral solution; and short-chain carboxylic fatty acids (SCFAs), including lactic, butyric and propionic, and citric acid, which are taken in a total quantity sufficient for maintaining the enteral solution's pH in a range from 4.61 to 5.8.

2. The acid-mineral composition of claim 1, characterized in that sodium phosphate mono-, or twice- or triple-substituted, and/or potassium phosphate mono- or twice-substituted, sodium chloride, sodium acetate, potassium chloride, calcium chloride, magnesium sulphate are used as said mixture of salts.

3. The acid-mineral composition of claim 2, characterized in that calcium chloride and magnesium sulphate are isolated from each other and from other components.

4. The acid-mineral composition of claim 2, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, triple-substituted, 12-aqueous—35.7-40.48; Sodium chloride—17.68-20.03; Potassium chloride—9.52-10.79; Calcium chloride—9.27-10.5; Magnesium sulphate—7.73-8.75; Na2EDTA or Na3DTPA—1.5-5.8; Citric acid, anhydrous—3.1-7.0; Lactic acid—1.48-4.9; Propionic acid—1.48-3.36; Butyric acid—0.74-1.68.

5. The acid-mineral composition of claim 2, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate twice-substituted 12-aqueous—33.0-36.48; Sodium chloride—20.24-22.34; Sodium acetate, 3-aqueous—4.0-4.43; Potassium chloride—9.08-10.03; Calcium chloride—8.85-9.77; Magnesium sulphate—7.37-8.14; Na2EDTA or Na3DTPA—1.47-5.4; Citric acid, anhydrous—2.95-4.56; Lactic acid—1.4-4.56; Propionic acid—1.4-3.13; Butyric acid—0.71-1.56;

6. The acid-mineral composition of claim 2, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, mono-substituted, anhydrous—16.29-17.92; Sodium chloride—22.34-24.59; Sodium acetate, 3-aqueous—18.76-20.64; Potassium chloride—10.03-11.04; Calcium chloride—9.77-10.75; Magnesium sulphate—8.14-8.96; Na2EDTA or Na3DTPA—1.63-5.95; Lactic acid—1.56-5.0; Propionic acid—1.56-3.44; Butyric acid—0.78-1.72.

7. The acid-mineral composition of claim 2, characterized in that it comprises the following ratio of components, wt %: Sodium chloride—29.63-32.73; Sodium acetate 3-aqueous—19.32-21.35; Potassium chloride—2.24-2.47; Potassium phosphate mono-substituted—14.91-16.48; Calcium chloride—10.17-11.24; Magnesium sulphate—8.47-9.36; Na2EDTA or Na3DTPA—1.69-6.22; Lactic acid—1.63-5.24; Propionic acid—1.63-3.59; Butyric acid—0.81-1.8.

8. The acid-mineral composition of claim 2, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, mono-substituted, anhydrous—5.99-6.71; Sodium chloride—30.82-34.5; Sodium acetate, 3-aqueous—9.72-10.88; Potassium phosphate, twice-substituted, 3-aqueous—15.51-17.36; Calcium chloride—9.99-11.18; Magnesium sulphate—8.32-9.31; Na2EDTA or Na3DTPA—1.66-6.18; Citric acid, anhydrous—3.33-5.22; Lactic acid—1.6-5.22; Propionic acid—1.6-3.58; Butyric acid—0.8-1.79.

9. The acid-mineral composition of claim 1, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, twice-substituted, anhydrous—16.85-19.09; Sodium chloride—25.13-28.46; Sodium acetate, 3-aqueous—4.98-5.64; Potassium chloride—11.28-12.78; Calcium chloride—10.99-12.45; Magnesium sulphate—9.16-10.37; Na2EDTA or Na3DTPA—1.83-6.89; Citric acid, anhydrous—3.66-5.81; Lactic acid—1.76-5.81; Propionic acid—1.76-3.98; Butyric acid—0.88-1.99.

10. An enteral solution for a lavage of a gastrointestinal tract and/or a correction of homeostasis disorders, comprising the acid-mineral composition of claim 1 and purified drinking water, said purified drinking water being comprised in an amount providing osmolarity of the enteral solution in a range from 280 to 310 mOsm/L and having a pH from 4.61 to 5.8.

11. The enteral solution of claim 10, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, triple-substituted, 12-aqueous—0.63-0.754; Sodium chloride—0.31-0.37; Potassium chloride—0.168-0.2; Calcium chloride—0.164-0.196; Magnesium sulphate—0.137-0.163; Na2EDTA or Na3DTPA—0.029-0.117; Citric acid, anhydrous—0.055-0.13; Lactic acid—0.026-0.091; Propionic acid—0.026-0.063; Butyric acid—0.013-0.031; Purified drinking water—97.9-98.4.

12. The enteral solution of claim 10, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, twice-substituted, 12-aqueous—0.61-0.73; Sodium chloride—0.375-0.45; Sodium acetate, 3-aqueous—0.074-0.089; Potassium chloride—0.168-0.2; Calcium chloride—0.164-0.196; Magnesium sulphate—0.137-0.163; Na2EDTA or Na3DTPA—0.029-0.117; Citric acid anhydrous—0.055-0.091; Lactic acid—0.026-0.091; Propionic acid—0.026-0.063; Butyric acid—0.013-0.031; Purified drinking water—97.78-98.35.

13. The enteral solution of claim 10, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, mono-substituted, anhydrous—0.273-0.327; Sodium chloride—0.375-0.448; Sodium acetate, 3-aqueous—0.315-0.376; Potassium chloride—0.168-0.2; Calcium chloride—0.164-0.196; Magnesium sulphate—0.137-0.163; Na2EDTA or Na3DTPA—0.029-0.118; Lactic acid—0.026-0.091; Propionic acid—0.026-0.063; Butyric acid—0.013-0.031; Purified drinking water—97.98-98.47.

14. The enteral solution of claim 10, characterized in that it comprises the following ratio of components, wt %: Sodium chloride—0.478-0.571; Sodium acetate, 3-aqueous—0.312-0.373; Potassium chloride—0.036-0.043; Potassium phosphate, mono-substituted—0.241-0.288; Calcium chloride—0.164-0.196; Magnesium sulphate—0.137-0.163; Na2EDTA or Na3DTPA—0.03-0.118; Lactic acid—0.026-0.091; Propionic acid—0.026-0.063; Butyric acid—0.013-0.031; Purified drinking water—98.06-98.54.

15. The enteral solution of claim 10, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, mono-substituted, anhydrous—0.098-0.118; Sodium chloride—0.507-0.605; Sodium acetate, 3-aqueous—0.16-0.191; Potassium phosphate, twice-substituted, 3-aqueous—0.255-0.304; Calcium chloride—0.164-0.196; Magnesium sulphate—0.137-0.163; Na2EDTA or Na3DTPA—0.03-0.118; Citric acid anhydrous—0.055-0.091; Lactic acid—0.026-0.091; Propionic acid—0.026-0.063; Butyric acid—0.013-0.031; Purified drinking water—98.03-98.53.

16. The enteral solution of claim 10, characterized in that it comprises the following ratio of components, wt %: Sodium phosphate, twice-substituted, anhydrous—0.252-0.301; Sodium chloride—0.376-0.449; Sodium acetate, 3-aqueous—0.075-0.089; Potassium chloride—0.169-0.202; Calcium chloride—0.164-0.196; Magnesium sulphate—0.137-0.164; Na2EDTA or Na3DTPA—0.03-0.118; Citric acid, anhydrous—0.055-0.092; Lactic acid—0.026-0.092; Propionic acid—0.026-0.063; Butyric acid—0.013-0.031; Purified drinking water—98.2-98.68.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The invention is explained by the illustrative materials which present a pattern of accelerated regeneration of a particular patient's GIT mucosa (according to the results of clinical observation), owing to the use of the proposed solution. FIG. 1/5 shows the pattern of damage caused to the mucosa at esophagus parts (chemical burn) of the patient before starting the treatment. FIGS. 2/5 and 3/5 show a pattern of the mucosa condition at various parts of the esophagus in 5 days. FIGS. 4/5 and 5/5 show the condition of the mucosa of the stomach and the duodenum, respectively, after the same period.

BEST MODE OF CARRYING OUT THE INVENTION

[0052] Preparation of the AMC and the Enteral Solution (ES)

[0053] The proposed solution may be prepared either in the ready-to-use form, or as a semi-finished product, i.e. an AMC set (comprising concentrates of all the ingredients, magnesium sulphate (in the form of powder or solution) and a calcium chloride solution being isolated from the other components). In the latter case, the user may prepare the solution himself, following the accompanying instructions. The AMC may be prepared as a series for a certain volume of the solution, e.g., 4.5 or 30 L, etc.; in this case, the total weight of the ingredients and the calculated volume of water are indicated.

[0054] The enteral solution may be prepared from the AMC in the following way. The AMC, except for the magnesium and calcium salts, is dissolved in two thirds of the stipulated volume of purified drinking water, then magnesium sulphate (in the form of powder or solution) and calcium chloride (in the form of solution) are added. After this, purified drinking water is added until the preset volume is reached.

[0055] The proposed solution is used as follows.

[0056] I. Intestinal Lavage

[0057] A minimal volume of the solution, which is required for effective irrigation of the GIT of an adult patient, is 3.0-4.5 L per one procedure. The intestinal lavage should be carried out on an empty stomach (a fasting period should be at least 5-6 hours). The procedure, especially the first one, should be conducted, preferably, in the morning. The solution is heated (up to 37-40° C.) before use.

[0058] The patient should drink the solution by portions of 150-200 mL every 5 minutes. Usually, the bowels start emptying by itself also by portions, after patients drink 1.5-2.5 L of the solution. The procedure should be continued until a time when excrements become clear (may have a yellowish color), then the patient stops drinking the solution, but defecation may continue for the following 30-40 minutes; then intestinal discharge stops. After 1-1.5 hours, the patient should receive food rich in edible fibers (porridges made of whole unpolished cereals with water without sugar, dried apricots). Later, the patient resumes taking food as usual, except for spicy and fatty foods, smoked products and alcohol within 2-3 days.

[0059] An average duration of the procedure is 3 hours. After an IL procedure, a patient may be engaged in usual business, without being concerned about diarrhea recurrence.

[0060] In cases where patients, due to their severe condition, may not take the solution on their own, specialists introduce it through a tube.

[0061] Indications for intestinal lavage:

[0062] 1. Exo- and endotoxicosis;

[0063] 2. Intestinal disbiosis;

[0064] 3. Acute and chronic hepatitis;

[0065] 4. Acute and chronic pancreatitis;

[0066] 5. Gastritis, enterocolitis;

[0067] 6. Dyskinesia of the biliary tracts;

[0068] 7. Constipation of I*III degree, having the functional nature;

[0069] 8. Infectious intestinal diseases;

[0070] 9. Chronic pyelonephritis;

[0071] 10. Diseases accompanied by skin damage (atopic dermatitis, neurodermatitis, psoriasis, eczema, acne, etc.);

[0072] 11. Acute and chronic allergic diseases;

[0073] 12. Bronchial asthma, inflammatory non-specific bronchopulmonary diseases;

[0074] 13. Diseases associated with hormonal disorders and metabolic disorders, including calcinosis (dermatomyositis, scleroderma, myositis ossificans), pathological skeleton ossification, arthritis with salt deposition, calcium deposition in the kidneys;

[0075] 14. Alcohol withdrawal syndrome, drinking bout, abstinence syndrome (including alcoholic hallucinosis, delirium);

[0076] 15. Chronic inflammatory diseases of small pelvis organs;

[0077] 16. Post-operational and traumatic enteroparesis;

[0078] 17. Burn disease;

[0079] 18. Radiation sickness;

[0080] 19. Oncological diseases;

[0081] 20. Preparations for planned operations and endoscopic examinations;

[0082] 21. Gas gangrene.

[0083] For prophylaxis of diseases, the IL procedure is recommended to patients:

[0084] after stresses, with errors in rations, whose ration comprises insufficient amount of fibers, practicing disorderly meals, having sedentary mode of life, disposed to obesity, subject to frequent catarrhal diseases, engaged in production with factors harmful for health, having bad habits.

[0085] Absolute contraindications are: intestinal obstruction of mechanical etiology (intestinal tumors, intestine scarry stricture, mechanical intestine squeezing from outside, etc.), gastrointestinal and other internal hemorrhages, threat and perforation of the GIT hollow organ, acute appendicitis, pregnancy second half, hypertensic crisis, acute cardiovascular pathology and pulmonary decompensation.

[0086] Relative contraindications are: cholelithiasis and urolithiasis, diabetes of I type, acute condition of hemorrhoid, pregnancy first half, hemophilia.

[0087] II. Nutritional Correction

[0088] A patient takes the solution by portions (e.g., 200 mL) for 1 day, the total volume is up to 1.5 L. If the solution is taken in a volume greater than 1.5 L, diarrhea may appear in an adult patient, i.e. the effect of intestinal lavage may come out.

[0089] Indications:

[0090] 1. Deficit of electrolytes in the organism (e.g. their loss with excessive sweat, during diarrhea associated with an intestinal infection, etc.);

[0091] 2. Functional disorders of the gastrointestinal tract;

[0092] 3. Acidosis, including that in sportsmen during a period of intensive physical loads; at alcohol withdrawal syndrome;

[0093] 4. Shock, including post-hemorrhagic shock;

[0094] 5. Radiation sickness;

[0095] 6. Post-operational period.

[0096] The claimed properties of the proposed solution are confirmed by the results of the studies conducted.

[0097] Nineteen male patients aged from 37 to 85, having severe intoxications by cauterizing liquids were observed. In 11 cases, intoxication was provoked by oral intake of a base, in 8 cases—a concentrated acetic acid. Chemical burns of the mucosa of mouth, pharynx, esophagus and stomach were identified in the result of the endoscopic examination—esophagogastroduodenoscopy (EGDS). Out of the total number of the patients, 13 have a stomach burn of 2-3 degree, 6 have a stomach burn of 3-4 degree. For 11 patients, including three with a stomach burn of 3-4 degree, intestinal lavage with the use of the proposed solution was included into a complex of medicinal measures (the observed group). The comparison group consisted of 8 patients receiving the standard therapy, who were subjected to the IL procedure with the use of an ESS (prototype).

[0098] The patients of the observed group were given 200 mL of the proposed solution every 5 minutes in the initial hours of the chemical trauma after administration of anesthetics and spasmolytics and tube lavage of the stomach. With due regard to the specifics of the intoxication (risk of hemorrhage), in these cases the solution was not heated, its temperature was 18-22° C. Diarrhea in patients appeared in 1.5-2 hours. The GIT was irrigated until light, semitransparent waters appeared from the rectum. The total volume of the solution was in the range from 3 to 4.5 L. The patients tolerated the IL procedure satisfactorily, no reactions and complications were identified. On the following days, the patients were given the same solution orally by 200-mL portions with the total volume of 1.5-3 L daily as nutritional correction.

[0099] The comparative assessment of the treatment results showed that clearly positive dynamics of the process of cleansing the damaged parts of the esophagus and stomach mucosa was recorded on Day 5, namely, necrotic masses disappeared, the thickness of fibrin layups decreased, areas of granulations appeared. By that time, no signs of regeneration of local defects on the esophagus and stomach mucosa were recorded. The pneumonia rate in the observed group and the comparison group was 18.2 and 37.5%, respectively. Two patients died in the comparison group, and the patients of the observed group remained alive, and an average hospitalization period of the latter was reduced by 25% in comparison with the former.

[0100] Thus, the use of the proposed solution in the complex therapy of cauterizing liquid intoxications facilitates acceleration of healing damaged areas of the mucosa, reduction of a pneumonia rate as a complication of intoxication by 48.5% and decrease of an average hospitalization period.

[0101] The following clinical observation may serve as an example of accelerated regeneration of the GIT mucosa owing to the use of the proposed solution.

[0102] Patient D. aged 44. Diagnosis: intoxication by acetic essence dated 17 Jan. 2017.

[0103] The first EGDS examination was conducted on 18 Jan. 2017 when the patient was taken to the hospital.

[0104] The description of the EGDS pattern: the esophagus mucosa was apparently edematous, with confluent circular layups of light fibrin of various densities. Multiple erosions were visible. The stomach mucosa was hyperemic, edematous with multiple acute erosions up to 0.2 cm in diameter with a clean bottom. The duodenum mucosa had confluent layups of light fibrin. The postbulbar mucosa was also hyperemic, edematous; multiple linear ulcerous defects with a clean bottom, which had a depth up to 0.2 cm, and linear erosions with a clean bottom were detected.

[0105] Conclusion: disseminated erosive-ulcerous burn esophagitis, disseminated erosive burn gastritis, disseminated ulcerous burn duodenitis.

[0106] FIG. 1 shows a pattern of damaged mucosa of esophagus parts (chemical burn) of a patient before start of the treatment.

[0107] In addition to a complex of standard therapy, on the first day the patient was subjected to an IL procedure following the above methodology with the use of the proposed solution in the volume of 4.5 L which was prepared according to the second variant of the formulation (specific weight of the ingredients in wt %): sodium phosphate, twice-substituted, 12-aqueous—0.61; sodium chloride—0.375; sodium acetate, 3-aqueous—0.074; potassium chloride—0.168; acids: citric—0.055, lactic—0.026, propionic—0.026 and butyric—0.013; Na2EDTA—0.029, calcium chloride—0.164; magnesium sulphate—0.137 and purified drinking water—98.35.

[0108] During the following 5 days, the same solution was administered to the patient orally, by 200-mL portions with the total volume of 2-3 L per day as the nutritional correction. No complications and side effect were recorded, the patient tolerated the solution intake well. The patient's status was improved, normalization of the water-electrolytic balance was recorded. On Day 5 of the medical measures, the patient was subjected to the second EGDS.

[0109] Description of the EGDS pattern dated 23 Jan. 2017:

[0110] Clearly positive dynamics of the burn surface condition: the esophagus—the mucosa is moderately edematous; fibrin is fragmented in the upper third; confluent circular layups of light fibrin of various densities remain in the middle third of the esophagus; the mucosa was cleaned from fibrin on the part from 35 to 40 cm. The esophagus mucosa is hyperemic, moderately edematous; the erosions were epithelized. The duodenum mucosa is hyperemic, edematous, ulcerous defects were cicatrized.

[0111] FIGS. 2 and 3 show the pattern of the mucosa condition at various parts of the esophagus in 5 days. FIGS. 4 and 5 show the condition of the mucosa of the stomach and the duodenum, respectively, after the same period.

[0112] The disease course was smooth, without complications, and resulted in the recovery.

[0113] The proposed technical solution is new, since it is not obvious from the state of the art. It has a significant distinction from the prototype, namely, it ensures a long storage period of the solution (for more than 1 year) and maintenance of its properties at heating due to preventing insoluble salts from forming therein; it ensures edema prophylaxis after an intestinal lavage procedure without the necessity of conducting an obligatory laboratory study of a blood plasma osmolality due to the range of solution osmotic pressure covering the physiological values of the blood plasma osmolality, which precludes excess enter of water into the blood from the GIT cavity during an IL procedure, facilitates shortening of a regeneration period of the gastrointestinal tract mucosa when it is damaged and inflamed, reduction of a rate of extraintestinal complications associated with hyperpermeability of the intestinal barrier due to prebiotic properties of the solution.

[0114] The improved consumer qualities of the proposed solution enable to produce it serially, store for a long time and transport, use not only in specialized medical facilities, but also in other facilities as well as in the ambulatory and field conditions, which expands the field of its applicability being more practically feasible and more ergonomic, as compared to the prototype.