WO2015080623A1 - Agent for the prevention of nausea and vomiting during pregnancy - Google Patents

Abstract

The invention relates to the field of medicine and the food industry and concerns a method for producing vitamin complexes in tablet form for preventing nausea and vomiting. Proposed is a vitamin complex in tablet form which exhibits a therapeutic and prophylactic effect against nausea and vomiting during pregnancy, characterized in that it contains ginger (Zingiber officinalis), in the form of dried root extract, folic acid, vitamin B6, a pharmacologically acceptable source of calcium, and the excipients sorbitol, magnesium stearate and silicon dioxide. Also proposed is a method for producing the above vitamin complex by granulation and drying under specific conditions, followed by compression. The agent is an effective, easy-to-use vitamin supplement with a therapeutic and prophylactic effect and a safe duration of administration.

Description

 Means for the prevention of nausea and vomiting during pregnancy

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 as 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 (US8435575 (B2) - 2013-05-07). The possibility of use in pregnant women is not described.

Known source CN101283786 (A) - 2008-10-15, describing a food supplement to prevent motion sickness in the car and vomiting and the 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 acids, and / or reflux reflux, is beneficial for pregnant women , including as a food additive (WO2013110812 (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.

 KR20030008446 (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

 Cellulose, Microcrystalline

 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 of obtaining these tablets, due to the significant content of auxiliary components, it is clear to a specialist that such a method is time-consuming.

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 of 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 natural extract, evaporation and drying. The ginger extract preparation thus obtained is compressed into a tablet coated with shell, with the addition of auxiliary substances, such as silicon dioxide, 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 B6, 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 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, the ginger family - Zingiberaceae, by water-alcohol extraction, followed by concentration and drying of the extract in vacuo -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 have a burning ginger taste, as well as sesquiterpenes, carbohydrates, proteins, and trace elements.

 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. It participates as a co-factor 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, transaminating, deaminating and decarboxylating 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 by the fact 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 from 70 ⁰ to 80 ⁰ C for 7-10 minutes, then with hot air at a temperature in the range from 50 ⁰ to 60 ° C, for 4 to 6 hours to a moisture content of 3-4%,

b the obtained dry granules are sieved, vibrated through sieves with sizes 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 - 80 mesh sieves

 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 1 1.4g of silicon dioxide and part of the magnesium stearate and powder are 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-efficiency 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 to 6 hours, during which every hour the stacker avoids particle agglomeration. Dried granules appear white-brown, uniform in 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 rocks, 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 0.7mg

 Vitamin B6 20mg

 Dry Ginger Root Extract 40mg

 Source of calcium

 (in terms of elemental calcium) 200 mg

 sorbitol 2 mg

 magnesium stearate 100 mg

 silicon dioxide 100 mg

 Example 5 Capsule Production Method

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

 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

Claim  1. Vitamin complex in the form of a solid dosage form, showing a therapeutic and preventive effect against nausea and vomiting during pregnancy, 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 complex according to claim 1, characterized in that as a pharmacologically acceptable source of calcium contains dicalcium phosphate or tricalcium phosphate.  3. The complex according to claim 1, characterized in that the solid form is a tablet.  4. The complex 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 paragraphs 1-4, 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, dioxide silicon, magnesium stearate, the mixture is subjected to wet granulation, dried in a high-performance fluidized bed dryer at a temperature of from 70 ⁰ to 80 ⁰ C for 7-10 minutes, then with hot air at a temperature in the range from 50 ⁰ to 60 ° C for 4-6 hours to a moisture content of 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.