HU205000B - Process for producing complex roborating composition - Google Patents

Abstract

A complex roborant (tonic) prepn. contains vitamins, provitamins, aminoacids, micro and micro elements (all wt. %); alone or in combination: 0.1-0.9 vitamin Al detimol); 0.01-0.1 vitamin B, (thiamine) 0.01-0.1 vitamin B2 (riboflavin); 0.2-1.0 vitamin B3 (nicotinamide), vitamin B5 (pantothenic acid); 0.1-0.5 panthenol; 0.05-0.5 vitamin B6 (pyridoxine) 0.0001-0.0005 vitamin B12 (cyanocobalamin); 0.01-0.2 vitamin C (ascorbic acid); 0.002-0.009 vitamin D (calcipherol); 0.002-0.01 vitamin D3, (chlolecolcipherol); 0.2-0.8 vitamin E (tocopherol); 1.0-2.0 (cholinechloride). - Amino acids: 0.01-0.1 glycine, 0.01-0.2 lysine and vital elements as salts. 0.001-0.005 of V; 0.0001-0.001 of Mo; 0.001-0.005 of Co; 0.001-0.01 of Mg; 0.001-0.005 of Mn; 0.001-0.02 of Ni; 0.001-0.02 of Cu; 0.01-0.05 of Zn. 0.001-0.01 B and 0.001-0.1 Fe, and in addn: 0.01-0.1 yeast, which contains at least 0.5 wt. % selerium. - The prepn. also contains emulsifiers, carriers antioxidants and tabletting excipients

Description

BACKGROUND OF THE INVENTION The present invention relates to a novel process for the preparation of a complex roboroidal composition using vitamins, provitamins, micronutrients and macronutrients required by physiological processes.

It is well known that living organisms of the highest degree of differentiation also need the continuous uptake of essential substances, which in the case of man is taken up by food and water. However, in most cases, the diet contains only a very small amount, in a bad proportion, sometimes not at all, or only occasionally, some of the essential substances, the lack of which for a long time manifests in the disturbance of physiological processes, decrease in enzymatic activities.

According to medical literature, similar to the production of animal nutrition, mass nutrition is based on the use of only a few highly cultivated food ingredients (potatoes, bread, rice, flour, dairy products, low meat, fat), so very often there is a need for supplementation by separate intake of vitamins, micronutrients and macronutrients. Particularly important is the intake of some rare micronutrients, e.g. selenium, molybdenum, etc. which are found in only a few special foods in the desired amounts.

In addition, several literature data (see, for example, Hungarian Patent No. 176,202) indicate that solutions containing certain micro- and macro-elements, as well as glycine and glycerol, may have therapeutic effects in certain disorders.

The preparation of the composition described in the above-mentioned patent has the disadvantage that the chemical and physical properties of the components have to be taken into utmost consideration. On the one hand, water solubility is essential, but the compatibility of the components must also be considered. Therefore, the claimed composition relates only to compounds containing macronutrients and micronutrients which cannot form precipitates with one another. In addition, the stability of the reconstituted formulation is less and less satisfying of modern requirements.

The literature for preparing solutions containing vitamin A is very rich. The main problem here is the solubilization of lipophilic and hydrophilic vitamins and vitamin-like substances. No. 138,791. According to the Hungarian patent, the hydrophilic and lipophilic vitamins were dispersed in an aqueous solution and an attempt was made to stabilize the dispersion with glycerol, propylene glycol. Similar solutions are disclosed in Nos. 149,547 and 152521. however, the result is unsatisfactory due to low vitamin concentrations.

Worthy solution is found in Resolution 185 533. Hungarian Patent No. 5,121,129, which discloses that hydrophilic and lipophilicamines are prepared in a system comprising a limited range of polyol and nonionic surfactant. However, no information is provided on how this system behaves when supplemented with a mixture of micro- and macro-elements required for physiological processes. Our own experiments indicate that system stability is greatly reduced, precipitations occur, and desired doses cannot be adjusted.

It is therefore an object of the present invention to provide a solution which is capable of producing the desired complex roborizing agent composition without fail.

The present invention is based on the discovery that the desired object can be perfectly achieved by adsorbing an aqueous colloidal solution of the vitamin mixture onto a large surface, inert carrier, and then adding the resulting powder mixture to compounds containing solid micronutrients and macronutrients. Compounds containing micronutrients and macronutrients may also be used in solubilized form by adsorbing the solution on the same large surface support.

With the above unexpected recognition, a highly homogenizable, dry, micro-emulsion can be formed which can be formulated without any further preparation steps (granulation, etc.).

The invention thus provides a process for the preparation of a complex roborification composition using vitamins, provitamins, amino acids, and macro- and microelements, such that

0.1-0.9% by weight of vitamin A (retinol) and / or

0.01-0.1% by weight of vitamin Bj (thiamine) and / or

0.01-0.1% by weight of vitamin B _r (riboflavin) and / or

0.2-1.0% by weight of vitamin B ₃ (nicotinic acid amide) and / or

0.1-0.5 wt% of vitamin B ₅ (pantothenic acid) and / or

0.1 to 0.5% by weight of panthenol and / or

0.05 to 0.5 wt% of vitamin B ₆ (pyridoxine) and / or

0.0001 to 0.0005% by weight _{B] 2} vitamin (cyanocobalamin) and / or

0.01-0.2% by weight of vitamin C (ascorbic acid) and / or

0.002-0.009% by weight of vitamin D (calciferol) and / or

0.002-0.01% by weight of vitamin D ₃ (cholecalciferol) and / or

0.2-0.8% by weight of vitamin E (tocopherol) and / or

1.0 to 2.0% by weight of choline chloride such as vitamin and provitamin and

0.01-0.1% by weight of glycine and / or

0.01-0.2% by weight of lysine as amino acid and

0.001 to 0.005% by weight of vanadium salt,

0.0001-0.001% by weight of molybdenum salt,

0.001-0.005% by weight of cobalt salt,

0.001-0.01% by weight of magnesium salt,

0.001 to 0.005% by weight of manganese salt,

0.001 to 0.005% by weight of nickel salt,

0.001 to 0.02% by weight of copper salt,

0.01-0.05% by weight of zinc salt and

0.001 to 0.01% by weight of a boron-containing compound, if desired

0.001-0.1% by weight of iron salt as vital elements compounds and

0.01-0.1% by weight of yeast containing at least 0.5% by weight of selenium is known per se as emulgen2

HU 205,000 Β, carriers, antioxidant, and other tabletting agent (s) and homogenized.

In a preferred embodiment, the aqueous solution of the hydrophilic vitamins and provitamins is mixed with an aqueous solution of the lipophilic vitamins in the presence of detergent and glycerol, the resulting vitamin mixture is admixed with an inert high-activity carrier, the resulting powder mixture with solid compounds and essential amino acids. and mixing, homogenizing and tabletting with excipients known per se in tableting.

The hydrophilic vitamins and provitamins used in the present invention are thiamine hydrochloride, riboflavin phosphate, pyridoxine hydrochloride, cyanocobalamin, panthenol, nicotinic acid amide, folic acid, biotin, ascorbic acid, choline chloride.

Preferably, the lipophilic vitamins A, D, E, and K or derivatives thereof are used in the process of the invention. As micronutrient and macronutrient compounds, we use ammonium molybdenate, ammonium vanadate, cobalt sulfate, magnesium sulfate, manganese sulfate, nickel sulfate, copper sulfate, zinc sulfate, boric acid, selenium-containing yeast, iron.

According to our experiments, aluminum oxide or silica gel or silicates are used as high surface inert carriers. It has been found advantageous to use Aerosil-200 as silica gel.

Glucose should be used as a tabletting aid.

In the process of the invention, the hydrophobic vitamin components (vitamin A oil, vitamin E oil, etc.) are treated with an emulsifier and then dissolved in a small amount of water and polyhydric alcohol. The solutions are mixed in the presence of colloidal silica gel, preferably Aerosil, to form a dry microemulsion. To ensure stability, the micronutrients, their salts or salts should be removed. The complexes are preferably prepared separately by powder mixing or by applying the solutions to a large surface support, preferably silica gel.

The powder product is homogenized and then, if necessary, encapsulated or tableted using additional excipients.

The main advantage of the process according to the invention is that it enables the processing of substances of various physical and chemical properties (vitamins, trace elements and macronutrients) of about 20-25 in a very simple and reproducible way into a useful product. A further advantage is that our solution avoids the granulation required for formulation (tableting, encapsulation) and the associated loss and depreciation. However, perfect homogenization of very small amounts in one step can be achieved by microemulsion formation.

The process according to the invention achieves precisely adjustable concentration limits. The components in the formulation are guaranteed to remain stable.

The beneficial effects of the composition of the present invention have been demonstrated in detailed studies. It has been found that the composition according to the invention has a very beneficial effect on physical fitness, improves well-being and strengthens the general condition of the body. Based on the clear indications of some subjects involved, it has been discovered that the composition of the present invention is particularly effective in protecting against adverse effects, irritation and even pain caused by weather changes (front effects).

The process of the present invention is illustrated by the following examples:

Example I

Solution 1: 5.2 g Vitamin A propionate (retinol propionate), 8.6 g Vitamin E (tocopherol), 0.1 g menadione, 0.1 g Vitamin Dj (cholecalciferol), 85.0 g dissolved in nonionic detergent (Tween-80) or Cremophor EL. Solution 2: 0.5 g Thiamin HCl, 1.4 g Riboflavin Phosphate Na, 0.9 g Pyridoxine HCl, 6.0 mg Cyanocobalamint, 4.5 g d-panthenol, 8.0 g nicotinic acid, 0.1 g folic acid, 20.0 mg biotin, 1.0 g ascorbic acid, 0.5 g Butyl hydroxy toluene

Dissolve in 180 ml of distilled water, 100 ml of 70% choline chloride and 100 ml of glycerol with gentle heating and stirring.

Solutions 1 and 2 are then mixed with 250 g of Aerosil-200 and mixed vigorously to form a dry microemulsion. To this mixture is added a powder mixture of the following micro and macro elements: 2 g of ammonium molybdenate, 15 g of ammonium vanadate sulphate, hanging cobalt sulphate, 25 g of magnesium chloride, 21 g of manganese sulphate, 5 g of nickel sulphate, 20.5 g of copper sulphate, 42 g of zinc sulphate and 30 g of boric acid.

Product: 881.2 g complex roborizer.

Example 2

The vitamins were prepared by dry microemulsion formation as in Example 1. However, the trace element concentrate is prepared as follows:

1.6 g Ammonium molybdate, 20.0 g Ammonium vanadate, sulphate, 15.0 g Cobalt sulfate 26.0 g Magnesium sulfate 20.4 g Manganese sulfate 6.0 g Nickel sulfate, 20.0 g Copper sulfate, 40.0 g Zinc sulfate 28.0 g boric acid, 50.0 g lysine,

HU 205,000 Β

50.0 g of Selekton B ₂ ,

Dissolve 523.0 g in distilled water and add 200.0 g Glycerol and 500 g Aerosil200 to give a dry powder product. The powder product was homogenized with 43 g of selenium-containing yeast and 167 g of iron fumarate and finally 290 g of D-glucose.

Product: 2475 g of complex roborizer.

Example 3 Tablet Preparation:

The following amounts of the mixture prepared in Example 2 are used for each tablet:

0.25 g Vitamin Concentrate,

0.08 g of trace element concentrate and

The mixture of glucose (0.67 g) was homogenized by blending and then directly tabletted.

Example 4

A) Trace element concentrate Weighing to I kg I tablet contains the active ingredient ammonium vana- DAT sulfate. 23,000g 0.0120 mg ammonium molib- Dena 1.625g 0.0026 mg cobalt carbonate 13.275 g 0.0245 mg basic Mg carbonate 33,000g 0.0400 mg manganese carbonate 18,250 g 0.0320 mg nickel carbonates 5.460 g 0.0100 mg cupric carbonate 11,250 g 0.0250 mg zinc carbonate 47,500 g 0.1120 mg Boric acid 28.750 g 0.0200 mg glycine 56.250 g 0.2250 mg L-ascorbic acid 50,000g 0.2500 mg Selection B-2 50,000g - Selenium yeast (0.8% Se) 42,800 g 0.0013 mg D-glucose ad 1,000,000 g ad 4.0000 mg B) Vitamin Concentrate Vitamin E 8,400 g 2.0000 mg Vitamin B ₂ 1,500 g 0.3500 mg Vitamin B ₆ 1,000 g 2.5000 mg Vitamin B ₁₂ 0.004 g 0.0010 mg Nicotinic Acids (Vitamin B ₃ ) 10,000g 2.5000 mg Ca-d pantothenate (Vitamin B ₅ ) 5,000g 1.2500 mg biotin 0.020 g 0.0050 mg Choline chloride 70% 72,000g 12.5000 mg Glycerol 72,000g -

A) Trace element concentrate · Weighing to 1 kg 1 tablet contains the active ingredient Antioxidant (Nipagin v. BHA) 0.100 g - Tween-80 10,000g - Aerosil-200 250,000g D-glucose ad 1,000,000 g 250.0000 mg

g tablet required:

0.250 g vitaminkoncentrátum, 0.004 g microelement concentrate 0.746 g shell. excipient (glucose) altogether: 1,000 g

Brief description of tablet manufacturing:

Product manufacturing takes place in three separate phases.

THE/

A) Production of trace element concentrate:

The production mixing equipment is supplied with the required powder pre-weighed and screened to 200 micron particle size. After 8 to 10 minutes of intensive homogenization, the powder mixture is placed in a polyethylene lined paper bag and pre-labeled, sealed.

B) Production of Vitamin Concentrate:

The prescribed amount of vitamin E acetate oil was emulsified in Tween-80. The other vitamins and antioxidants are rubbed with glycerol and 70% choline chloride separately, and the previously emulsified vitamin E is added. Intensive mixing forms an emulsion and then mixes the emulsion with the required Aerosil in small portions. The homogeneous powder mass is broken through a silk screen (max. 500 microns) and intensively homogenized with the required amount of screened glucose. Acetate phthalate may also be used as an excipient.

Product homogenization:

0.250 g of vitamin concentrate per tablet are homogenized in a mixer with 0.004 g of micronutrient concentrate and 0.746 g of granulation aid (glucose), with water up to max. It is pulverized with 1-2% PVP and directly tableted. The finished tablets are packaged as soon as possible in an oxygen barrier triplex film or other container.

Claims (2)

PATIENT INDIVIDUAL POINTS 1. A method of producing a complex robotic composition using vitamins, provitamins, amino acids, macro- and microelements, comprising: 0.1 to 0.9% by weight of vitamin A (retinol) and / or 0.01-0.1 wt% _r B vitamins (thiamine) and / or 0.01 to 0.1% by weight of vitamin B ₂ (riboflavin) and / or 0.2 to 1.0 wt% of vitamin B ₃ (nicotinic acid amide) and / or 0.1-0.5 wt% of vitamin B ₅ (pantothenic acid) and / or 0.1-0.5% by weight of panthenol and / or EN 205 000 Β 0.05 to 0.5 wt% of vitamin B ₆ (pyridoxine) and / or from 0.0001 to 0.0005 wt% of vitamin B ₁₂ (cyanocobalamin), and / or 0.01-0.2 wt% of vitamin C (ascorbic acid) and / or 0.002-0.009% by weight of vitamin D (calciferol) and / or 0.002 to 0.01 wt% vitamin D ₃ (cholecalciferol) and / or 0.2-0.8 wt.% Of vitamin E (tocopherol) and / or 1.0-2.0 wt.% Of choline chloride as vitamin and provitamin and 0.01 to 0.1 wt. -0.2% lysine as amino acid and 0.001-0.005% vanadium salt, 0.0001-0.001% by weight molybdenum salt, 0.001-0.005% by weight of cobalt salt, 0.001 to 0.01% by weight of magnesium salt 0.001-0.005% manganese salt, 0.001-0.005% by weight nickel salt From 0.001 to 0.02% by weight of copper salt 0.01 to 0.05% by weight of zinc salt and 0.001 to 0.01% by weight of boron-containing compound, if desired 0.001-0.1% by weight of iron salt as compounds of vital elements and 0.01% to 0.1% by weight of yeast containing at least 0.5% selenium are mixed with emulsifiers, carriers, antioxidants and other tableting excipients known per se and formulated by homogenization. 2. The method of claim 1, wherein the aqueous solution of hydrophilic vitamins and provitamins is mixed with an aqueous solution of lipophilic vitamins in the presence of a detergent and glycerin, and the resulting vitamin mixture are mixed with an inert, high surface carrier, and the resulting powder mixture is essential. mixed with solid compounds, amino acid and yeast of the elements and with excipients known per se in tableting, homogenized and tableted.