RU2540508C1 - Agent for prevention of nausea and vomiting of pregnancy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: agent in the form of a vitamin complex applicable for replenishment of the deficiency of various nutrients in the body and in diseases related to the deficiency, as well as to prevent nausea and vomiting in the form of tablets exhibiting the therapeutic effect on nausea and vomiting of pregnancy, characterised by the fact that it contains ginger (Zingiber officinalis) in the form of dry extract of roots, folic acid, Vitamin B6, a pharmacologically acceptable calcium source and additives - sorbitol, magnesium stearate and silicon dioxide. What is also presented is a method for preparing it by granulating and drying in the certain environment and pressed.

EFFECT: agent represents the effective, easy-to-use vitamin additive with the therapeutic effect, which has the safe length of administration.

5 cl, 5 ex

Description

The invention relates to the field of medicine and the food industry and relates to a method for producing tablet vitamin complexes that prevent nausea and vomiting.

Vitamin complexes are used to fill the deficit of various nutrients in the body and in diseases associated with their deficiency.

Especially important is the inclusion of vitamins in the diet of pregnant women. If ordinary vitamin complexes contain certain lists of vitamins, then the composition of prenatal vitamins, that is, vitamins that play an important role in the body of pregnant women, as a rule, include folic acid, calcium and iron. These components are especially important for expectant mothers. At the same time, eating food that is rich in a variety of nutrients is not canceled. But taking vitamins helps compensate for the deficiency of their intake with food and can reduce the intensity of such unpleasant manifestations of an initial pregnancy, like nausea and vomiting.

A known method of obtaining a composition for the treatment of nausea and vomiting in cancer patients in the form of a capsule containing ginger and tocopherol (US 8435575 (B2) - 2013-05-07). The possibility of use in pregnant women is not described.

Known source CN 101283786 (A) - 2008-10-15, describing a food supplement to prevent motion sickness in the car and vomiting, and a method for its preparation. The supplement includes orange peel, ginger and brown sugar. The production method includes the following steps: boiling raw materials, concentration and granulation.

The prior art composition containing ginger powder, in combination with fillers, the process of its preparation, as well as its use for the treatment or prevention of nausea and / or vomiting and / or heartburn, ski acid, and / or reflux reflux, is beneficial for pregnant women , including as a food additive (WO 2013110812 (A1) - 2013-08-01). The tool is made in the form of a gel. Not described is a method of producing tablets.

The above sources and many others reveal the fact that ginger is an excellent remedy for nausea during pregnancy. But, despite the fact that quite a lot of medical studies have shown the effectiveness of ginger against nausea during pregnancy, it cannot be said that this is a universal remedy. In some women, ginger can exacerbate symptoms, provoke new problems, such as heartburn.

KR 2003 0008446 (A) - 2003-01-29 discloses a composition for the alleviation of nausea and vomiting of pregnant women (NVP). The described composition includes 60% or more by weight of ginger powder, 2 to 8% by weight of vitamin B6, 10 to 15% by weight of apricot powder and an additional 10 to 15% Chaenomeles sinensis powder by weight of the total weight of the composition.

The composition does not contain important prenatal vitamins in sufficient quantities.

Commercial name B-Nexa® tablets are available that contain vitamins that are essential in nutrition and are designed to help soothe pregnant nausea and vomiting. Composition of tablets:

Folic Acid 1.2 mg

Calcium 124.1 mg

Ginger 100 mg

Microcrystalline Cellulose

Maltodextrin

Talc

Corn starch

Croscarmellose Sodium

Stearic Acid

Hypromellose

Silica

Titanium dioxide

Hydroxypropyl cellulose

Magnesium Stearate

Iron Oxide Yellow

Iron Oxide Red

http://www.drugs.com/pro/b-nexa-tablets.html

The created tablets eliminate a number of disadvantages of the known complexes. However, allergic reactions have been reported when taking the tablets. Although the prior art does not disclose a method for producing these tablets due to the significant content of auxiliary components, it is clear to the skilled person that such a method is labor intensive.

As the closest analogue, a method for producing a galenic form of ginger extract, including tablets for the treatment of dyspeptic diseases, symptoms of motion sickness, as an antiemetic agent, as an antidiabetic agent, as an analgesic, and treatment of vomiting related to pregnancy or caused by chemotherapy, for the treatment of rheumatic diseases or as food additives (patent RU 2289420). A method for preparing a stable preparation of dry ginger extract includes extraction of crushed ginger roots to obtain a liquid extract solution, concentrating a liquid extract solution to obtain a viscous extract, diluting a viscous extract, adding a solution of polyvinylpyrrolidone as a stabilizing auxiliary agent with a certain ratio of auxiliary agent to the natural extract, evaporation and drying. The ginger extract preparation thus obtained is compressed into a coated tablet by the addition of excipients such as silica, maltodextrins, magnesium stearate, cellulose or carboxymethyl starch.

The objective of the invention is to develop a method for producing funds in the form of a vitamin complex, suitable for filling the deficiency of various nutrients in the body and for diseases associated with their deficiency, as well as to prevent nausea and vomiting.

The resulting product contains a vitamin active complex, including folic acid, Vitamin B 6, a pharmacologically acceptable source of calcium, ginger Zingiber officinalis in the form of a dry root extract and excipients, including Sorbitol, Magnesium stearate, silicon dioxide, in the following components, in mg:

Folic acid 0.7-1.5 mg

Vitamin B6 20-50 mg

Dry extract of ginger roots 40-120 mg

Source of calcium

(in terms of elemental calcium) 80-350 mg

Sorbitol 1.5-2 mg

Magnesium stearate 100-120 mg

Silicon dioxide 100-120 mg.

This product is an effective, easy-to-use biologically active food supplement or vitamin supplement with a therapeutic and prophylactic effect. The tool is made in the form of a vitamin complex, suitable for filling the deficiency of various nutrients in the body and for diseases associated with their deficiency, as well as for preventing nausea and vomiting. The tool is made in the form of a solid dosage form, such as granules, tablets, capsules.

Usage: oral, safe duration of admission at least 24 months.

Ginger, according to the present invention, is used in the form of a well-known official dry extract (http://www.rlsnet.ru/prep_index_id_340354.htm), which is obtained from crushed dried roots (rhizomes) of cultivated ginger Zingiber Officinale, ginger family - Zingiberaceae, by water method -alcohol extraction, followed by concentration and drying of the extract on a vacuum spray dryer. It is a brownish or brownish-yellow fine powder with a characteristic odor and specific taste.

Active substances: “gingerol”, which consists of gingerol, cingerol, paradol, shogaol and other resins, which are associated with a burning ginger taste, as well as sesquiterpenes, carbohydrates, proteins, microelements.

The extract has anti-nausea and antiemetic, tonic, restorative, anti-aging, anti-platelet, analgesic, emollient, sedative, stimulating cell metabolism, anti-inflammatory, bactericidal, antimicrobial effects. Gingerols included in the composition improve digestion and metabolism.

Folic acid refers to the water-soluble vitamins of group B. It is also known as folacin, or vitamin B9. Folic acid is essential for fetal development. She participates as a cofactor in a large number of important cellular reactions. Folic acid is a substrate for various biochemical reactions (such as transmethylation and transulfonation) associated with the metabolism of certain amino acids (series, glycine, methionine, histidine). During gestation, folate-dependent processes are the growth of the fetus, uterus, placenta and mammary glands, as well as an increase in the number of red blood cells. Thus, during pregnancy, the need for this vitamin increases dramatically.

Vitamin B6 (pyridoxine) is required as a cofactor for amino acid metabolism enzymes, including enzymes that transamine, deamine and decarboxylate amino acids. Pyridoxine reduces the severity of nausea and vomiting.

Pharmacologically acceptable sources of calcium may be calcium salts such as carbonate, calcium phosphate, calcium citrate, calcium gluconate, calcium lactate, etc., preferably dicalcium phosphate or tricalcium phosphate. Calcium is necessary for blood formation, metabolism, reduction of vascular permeability, for normal bone growth (skeleton, teeth); beneficial effect on the state of the nervous system, has an anti-inflammatory effect.

However, in order for the indicated active principle of the vitamin supplement to show all its properties, it must be obtained in a form convenient for administration. This is possible with the right choice of excipients. In addition, the choice and certain modes of the process will give the tablet the necessary hardness, improve mechanical stability, achieve the desired solubility, a predetermined release time, optimize bioavailability, solve problems with active substances that are sensitive to moisture or temperature effects. The choice of excipients (or adjuvants) has a significant effect on the pharmacological activity of the finished drug. The object of the present invention in addition to the optimized composition of the tool is a method for its preparation.

The production method is characterized in that folic acid, vitamin B6, a pharmacologically acceptable source of calcium, dry extract of ginger roots are mixed in dry form, mixed with a binder in the form of a solution containing sorbitol, silicon dioxide, magnesium stearate, the mixture is subjected to wet granulation, dried in a highly effective a fluidized bed dryer at a temperature of 70 ° to 80 ° C for 7-10 minutes, then with hot air at a temperature in the range of 50 ° to 60 ° C, for 4-6 hours to a moisture content of 3-4%, the resulting dry screening granules t, vibrate through sieves with dimensions of 14-16 mesh, dusted with magnesium stearate and subjected to molding.

The invention can be illustrated by the following embodiments.

Example 1

The composition of the vitamin complex per 1 tablet:

Folic Acid 1.22 mg

Vitamin B6 42 mg

Dry Ginger Root Extract 100 mg

Source of calcium

(in terms of elemental calcium) 327 mg

Sorbitol 1.78 mg

Magnesium stearate 114 mg

Silicon Dioxide 114 mg

Example 2

The method of preparation of tablets of the vitamin complex (calculation per 100 pieces)

1. Weighing, dosing of raw materials.

Sorbitol, silicon dioxide is sieved through 100 mesh sieves, magnesium stearate is sieved 80 mesh.

During visual inspection of the crushed material there should not be any foreign objects, there should not be a color change.

Particles larger than 100 mesh are screened and transferred to additional crushing.

2. Granulation

- Cooking binder

Take 0.178g of Sorbitol and 11.4g of silicon dioxide and a portion of Magnesium stearate, and the powder is used to prepare a syrup with water. Heating at a vapor pressure of 0.1-0.3 MPa. The resulting binder solution is filtered through a 20 mesh sieve.

- Wet granulation process

Folic acid, vitamin B6, calcium, ginger extract are mixed in dry form for 3-4 minutes. A binder is added and mixing lasts from 3 to 4 minutes.

The resulting material has a soft consistency. It is granulated through a 14-16 mesh nylon sieve. Get the granules of the same size.

3. Drying

- high-performance drying in a fluid bed dryer type "GFG-120". The vapor pressure is 0.2 to 0.3 MPa, with a transition to air pressure from 0.1 to 0.15 MPa. Drying with controlled temperature from 70 degrees to about 80 degrees for 7-10 minutes. Get the dried granules white-brown, uniform color, without foreign inclusions.

- drying with hot air in a thermostat at a temperature in the range from 50 degrees to 60 ° C, for 4-6 hours, during which every hour the stacker must avoid particle agglomeration. Dried granules of white-brown, uniform color, without foreign inclusions. Moisture should be between 3% and 4%.

4. Preparation of the composition for molding

Vibration through sieves 14 mesh.

Dusting: dry granules and part of magnesium stearate are mixed for 20-30 minutes at a speed of 20 to 30 revolutions / min.

5. Molding by tablet compression

Carried out on a rotary tablet machine ZP-19F.

6. Packing

Use plastic bottles. Each bottle has a row of at least 60 tablets.

Example 3

Technological characteristics

Tablets obtained from the pharmaceutical composition of the present invention have acceptable physical characteristics, including optimal hardness, which provides resistance to chips, abrasion during storage and transportation.

The measurement was carried out by a standard test by weighing 20 tablets, placing them in a rotating plexiglass drum, in which they were lifted during repeated cycles using a circular lever (25 rpm) and dropped from a certain height. Spend about 100 cycles, the tablets are re-weighed and calculate the percentage of the composition, subjected to abrasion or chipping. The fragility of the tablets of the present invention is preferably in the range of from about 1-1.5%.

Example 4

Capsules

Folic Acid 0.7 mg

Vitamin B6 20 mg

Dry extract of ginger roots 40 mg

Source of calcium

(in terms of elemental calcium) 200 mg

Sorbitol 2 mg

Magnesium Stearate 100 mg

Silicon dioxide 100 mg.

Example 5

The method of obtaining capsules

The method is carried out as described in example 2, except that at the stage of forming granules with dusting substance, hard gelatin capsules are filled.

Tests on volunteers showed excellent tolerance and a significant improvement in well-being with nausea, the elimination of vomiting reflexes.

The proposed tool can be used not only for pregnant women, but also as a vitamin remedy for debilitated patients, patients suffering from motion sickness in vehicles, etc.

Claims (5)

1. A tool in the form of a vitamin complex suitable for filling the deficiency of various nutrients in the body and for diseases associated with their deficiency, as well as for preventing nausea and vomiting, characterized in that it contains Zingiber officinalis ginger in the form of a dry root extract, folic acid Vitamin B6, a pharmacologically acceptable source of calcium and excipients - sorbitol, magnesium stearate and silicon dioxide, in the following components, in mg:
Folic Acid 1-1.5 mg
Vitamin B6 35-50 mg
Dry extract of ginger roots 80-120 mg
Source of calcium
(in terms of elemental calcium) 80-350 mg
Sorbitol 1.5-2 mg
Magnesium stearate 100-120 mg
Silicon dioxide 100-120 mg. 2. The tool according to claim 1, characterized in that as a pharmacologically acceptable source of calcium contains dicalcium phosphate or tricalcium phosphate. 3. The tool according to claim 1, characterized in that the solid form is a tablet. 4. The tool according to claim 1, characterized in that the solid form is a capsule. 5. The method of obtaining the complex according to any one of claims 1 to 4, characterized in that folic acid, vitamin B6, a pharmacologically acceptable source of calcium, dry extract of ginger roots Zingiber officinalis are mixed in dry form, mixed with a binder in the form of a solution containing sorbitol, silicon dioxide, magnesium stearate, the mixture is wet granulated, dried in a high-performance fluidized bed dryer at a temperature of 70 ° to 80 ° C for 7-10 minutes, then with hot air at a temperature in the range from 50 ° to 60 ° C for 4 -6 hours before being held in lags 3-4%, the obtained dry granules are sieved, vibrated through sieves with sizes of 14-16 mesh, dusted with magnesium stearate and subjected to molding.