RS51374B - USE OF NATURAL AND SYNTHETIC EUGENOL AS A FEED ADDITIVE - Google Patents

Abstract

The use of natural and synthetic eugenol as a feed additive based on natural eugenol obtained from essential oils: camphor wood (Cinnamomum camphora Sieb), idjirota (Acorus calamus L.), cironella from Java (Cymbopogon winterianus Jowitt), ylang Canga yum Baill.), Cananga (Cananga odorata Hook.), Nutmeg (Myristica fragransHoutt), sassafras (Sassafras albidum Nutt.), Myrrh (Commiphora myrrha Nees), bay leaf (Laurusnobilis L.), California laurel (Umbellulatria californica) galangalange (Alpinia officinarum Hanee), apricot (Acacia farnesiana Willd.), basil (Ocimum minimum or Ocimum gratissimum L.) and violet (Viola odorata L.), characterized in that ¬increased acidity of the phenolic hydroxyl group, which with dilute aqueous solutions of alkali builds stable in water soluble salts, and which are not volatile under the influence of water vapor. The application contains 6 more dependent patent claims.

Description

Technical field

The application of natural and synthetic eugenol as an additive to animal feed in the prevention and treatment of animal diseases generally refers to the field of application of substances incorporated into veterinary preparations, and specifically refers to the procedure of obtaining veterinary preparations based on natural and synthetic eugenol, and essential oils from plants containing eugenol (cloves, allspice and cinnamon leaves) and their application in the prevention and treatment of animal diseases caused by bacteria, fungi and parasites.

According to the International Classification of Patents (IPC, Int.Cl. ), the subject of the invention is classified and marked with the classification symbol A61K 31/775 (2010.01) which refers to medical preparations containing active organic ingredients, as well as secondary classification symbols A61K 31/74 (2010.01) which define medical preparations containing synthetic polymer substances and C08K 5/105 (2010.01) which refers to the use of organic substances as ingredients for mixtures with phenols.

Technical problem

The technical problem that is solved by the present invention consists in the following: how to apply natural and synthetic eugenol that is added to animal feed and whose active principles of action of the ingredients that make it up, completely or to a significant extent, affect the prevention of the cycle of reproduction of bacteria, fungi and parasites, resulting in their destruction, which achieves more effective preventive protection of animals from to their destruction, which achieves more effective preventive protection of animals, i.e. treatment, and enables the substitution of antibiotics, sulfonamides and of coccidiostat preparations, whereby the application of eugenol enables the animal feed containing it to be used without interruption during the entire upbringing, to be tolerated by the animals more easily and to be given without side effects and contraindications.

State of the art

Modern intensive production of meat, milk and eggs, due to economic justification, requires keeping a large number of animals in as little space as possible. Large concentrations of animals represent a good basis for the outbreak of diseases, especially gastrointestinal infections, both in young animals and in older categories. For this reason, antibiotics, sulfonamide preparations, and coccidiostats have been used for tens of years to prevent the occurrence of animal diseases. Adding some of the mentioned types of drugs into food or water for animals gave effective results in disease prevention. Until 15-20 years ago, unfortunately, not much was thought about the negative consequences that can arise from such a preventive measure, and they appeared in the form of: bioresidues in milk, meat and eggs, as a result of the deposition of antibiotics and other preparations. Microorganisms against which these preparations were used became resistant (resistant) to the mentioned preparations over time. By using animal products with accumulated bioresidues for his diet, Covck made many bacterial species in his body resistant to various types of antibiotics and sulfonamides.

In order to prevent these and other unwanted consequences, the more economically developed countries of Europe, the USA and Canada have adopted a series of measures that prevent or reduce the use of antibiotics and sulfonamides for nutritional and preventive purposes, while simultaneously introducing regulations that prevent the circulation of products (milk, meat, eggs) that contain bioresidues.

In the expert article "Antibacterial Activity of Standard F.ugenol against Salmonella/ hi spp. (Antibactericidal activity of standard Eugenol on salmonella) N'ucha Simasaticul et al. (Consulting Tropentag, October 7-9, 2008, Hohenchim, Germany) discussed the issue of the action of eugenol in the prevention of animal diseases caused by salmonella.

In the journal Kasetart Journal odcljak Nat.Sci 41(2007) pp. 319 - 323, the authors P. Tippavatum and V. Chonhenchob in the article "Antibacterial Activities of Thymol, Eugenol and Nisin Against Some Food Spoilage Bactria" (Antibacterial activity of thymol, eugenol and nisin on some bacteria that cause food spoilage) gave an account of the positive effect of the mentioned ingredients on the prevention of food spoilage, which should be typed and taken to the market, where it should remain packed until use.

Authors S.K. Oxenham, K..P. Svoboda and D.R. VVallcrs in the journal Phytoparasitica 33(2005)3 p. 247 to 252 in the article "Eugenol Reduces Growth and increases Activity of S-adenosylmethionine Dccarboxylase in the Phytopathogenic Fungus Botrvtis Jahač"(Eugenol reduces growth and increases the activity of S-adenosylmethionine decarboxylase in the phytopathogenic fungus Butrrlis faha) show the effects of the action of eugenol in reducing growth in the polyamine metabolism of this fungus, which is later more widely applied in the prevention of various diseases in animals.

On the basis of the above and his own long-term research, the author of the subject invention decided to develop a preparation, which contains ingredients whose reception can significantly or completely overcome the problems and limitations associated with the long-term use of antibiotic and sulfonamide preparations.

Presentation of the essence of the invention

The essence of the application of natural and synthetic eugenol and essential oils from cloves, allspice and cinnamon leaves, as an additive to animal feed, in the prevention and treatment of animal diseases, according to this invention, is reflected in the finding and application of a substance that, integrated into the subject animal feed additive, shows positive results in the prevention and treatment of animal diseases caused by bacteria, fungi and parasites. The mode of action of natural and synthetic eugenol as an additive to animal feed, according to the invention, is different from the action of classical preparations, which is primarily reflected in the increase of their efficiency and the acquisition of a number of other positive characteristics. This was achieved by using natural eugenol. eugenol in the form of sodium and potassium salts and essential oils from plants containing eugenol, using its properties as an antiseptic and bactericide, i.e. its ability to act as an antioxidant.

The essence of the invention is also reflected in the fact that feed additives containing natural eugenol, eugenol in the form of sodium and potassium salts and essential oils from plants containing eugenol (clove, allspice and cinnamon leaf) act on bacteria, fungi and parasites by:

1. They damage the cytoplasmic membrane by breaking down membrane lipids:

2. They prevent the synthesis of albumin in the cytoplasm, which is responsible for transporting oxygen to the mitochondria; 3. They lead to the rapid death of bacteria, fungi and parasites due to lack of oxygen.

The essence of the invention is reflected in the fact that animal feed additives, in which natural eugenol, eugenol in the form of sodium and potassium salts and essential oils from plants containing eugenol are used, are potent entero-septics and are a successful substitute for antibiotics, sulfonamides and coccidiostat preparations.

The main advantages of using natural and synthetic eugenol as an additive to animal feed, in the form of sodium and potassium salts of eugenol and essential oils from plants containing eugenol according to this invention compared to other means used in the prevention and treatment of diseases caused by bacteria, fungi and parasites are reflected in the following: - active substances in the preparations based on this invention are of natural, plant origin and are not antibiotics, which is why they are not deposited in meat. milk and eggs, and they have no withdrawal period. what is the main problem with antibiotic and sulfonamide preparations; - more efficient and reliable action with the avoided risk of sudden and unexpected resistance formation; - animals tolerate them easily without any harmful consequences; - animals accept them more easily in stronger doses than standard preparations that are widely used today; - eugenol as an additive to animal feed can be used continuously, without interruption, because it does not settle in meat, milk and eggs, so that the protection of animals is achieved during the entire upbringing.

Detailed description of the invention

Natural eugenol

Eugenol is widely distributed in aromatic and spicy plants belonging to the family Mvrtaceae and Lauraceae. Eugenol is the main constituent of clove oil {Eugenia carvophvllataThumb.). oimente (Pimenta ofjicinalis Lindlev) and cinnamon leaf (Cinnaniomum zevlanicum Nees).

Eugenol is also a component of essential oils: camphor tree (Cinnamoinum camphoraSieb), idjirota (Acorus calaimis L.). cironelc from Java (Cvmhopogon winterianitsJowitt.), ylang ylang tree (Canangium odoratumBaill.). kananga (Cananga odo-ra taHook.), walnut (Mvristica JragransHoutt.k sassafras (Sa. s. safras (dhiduinNutt.), myrrh {Cominiphora mvrr/ taNees), bay leaf (Lauriis nohi/ isL), California laurel (Umhe/ lu/ aria californicaNutt.), galangal bark (Alpinia ofjici-naruntHanec). cassia (Acacia Jarnesiana Willd.) basil (Ociinum minimumiOcimum gratissimii/ iiL.) and violets (Viola odorala 1..)

Natural eugenol is obtained from essential oils with a high eugenol content. To separate eugenol from other accompanying components of essential oil, the chemical property of eugenol is used, which is based on the increased acidity of the phenolic hydroxyl group, which forms stable water-soluble salts with diluted aqueous alkali solutions that are not volatile under the influence of water vapor.

Synthetic eugenol

In addition to natural eugenol, synthetic eugenol is also known as 2-methoxy-4-(2-propenyl) phenol, CAS number 97-53-0. This eugenol is also known under the names; 4-allyl-2-methoxyphenol, allylguaiacol, eugenic acid and caryophyllic acid, molecular formula CioH^O?molecular weight 164.20.

The structural formula of eugenol is shown in Figure 1.

Eugenol is a colorless liquid (it darkens on evaporation and in contact with air), boiling point 252.60° C. It can be distilled at atmospheric pressure without significant decomposition. It smells like cloves, spicy. taste that "burns". The melting point is from -9.2<0>C to -9.1°C. Gustinad20/4 1.0664. Refractive index n 20/D 1.5410.

The solubility of eugenol in water-alcohol and alkaline water environments is significant. One volume of eugenol dissolves in 5-6 volumes of 50% alcohol, 2-3 volumes of 60% alcohol or 1-2 volumes of 70% alcohol. One mL of eugenol is dissolved in 4.27 mL of 50% alcohol at 25°C, while dissolving the same amount at 15°C requires 5.22 mL of alcohol of the same concentration. 12.7 mL of a 2% solution of sodium hydroxide in water dissolves 1 mL of eugenol.

The phenolic hydroxyl group gives characteristic reactions. With ferric chloride in aqueous solution it gives a dark turbidity, while in 2% alcohol solution a blue color appears. Hydroxyl group can be translated into ester or ether.

In the immediate vicinity of the phenolic hydroxyl group, the 2-methoxy group, with its strong negative inductive effect, attracts the electron pair of the O-H bond and enables the easy departure of H' ions, that is, it contributes to the increased acidity of the molecule. In comparison with phenol and similar structures such as carvacrol and thymol. eugenol is significantly more acidic. It easily reacts with carbonates and bicarbonates, and blue litmus colors red. Homolytic dissociation of the O-H bond is also known, which leads to the formation of free oxygen radicals. This can be an advantage when it is used as a catalyst in some radical polymerization reactions (for example in dentistry). Ionization of the O-H bond, i.e. the formation of an O" Me ion pair prevents the formation of oxygen free radicals. Possible metals that can create an ion pair are sodium and potassium in cases where the intention is to use eugenol per orally, i.e. zinc if the use of eugenol is in dermatology.

Eugenol obtained in this way has bactericidal and fungicidal properties and is used as an antiseptic, preservative, antibiotic and antimycotic in pharmaceutical and veterinary preparations, perfumes and cosmetic preparations, toothpastes and soaps. It is used externally, in the form of pastes, and by inhalation, i.e. in the form of oral preparations. Unlike some structurally very similar synthetic phenols (eg guaiacol), it is characterized by increased efficiency, easy tolerability and non-toxicity. Although in some cases pure eugenol can cause irritation in contact with the skin and mucous membranes, it can be considered practically non-toxic in oral applications (LD.so orally in rats 2680 mg/kg, in mice 3000 mg/kg).

In order to demonstrate the feasibility of the invention, a method of removing the accompanying components of eugenol by extraction is given.

This method is based on the property of eugenol that with a 3% aqueous solution of sodium hydroxide (NaOl I) it forms a water-soluble salt, sodium eugenolate, which is poorly soluble in organic nonprotic solvents such as diethyl ether and petroleum ether. The semi-liquid components of the essential oil are extracted with petroleum ether in a continuous liquid-liquid extraction process. The aqueous solution is acidified (with ortho phosphoric acid) to pH 4 and distilled using steam. After separating the (lower) oily phase, it is dried and distilled under reduced pressure. Table 1 shows the dependence of the boiling point of eugenol on the pressure under which it is distilled.

The purity of the obtained product is > 99% (area GC).

In order to prove the feasibility of the invention, the method of obtaining eugenol by removing the accompanying components by distillation is also given: This method is based on the property of eugenol to form a water-soluble salt with a 3% aqueous solution of sodium hydroxide (NaOH). sodium eugenolate, which is stable enough at 100° C. so that only the accompanying components of the tar oil are distilled by steam distillation. At the end of the distillation, the aqueous solution is acidified (with ortho phosphoric acid) to a pll value of 4 and distilled using steam, when pure eugenol is distilled. After separating the (lower) oily phase, it is dried and distilled under reduced pressure. During the distillation of the accompanying components, which are made up of terpenes; a-pinene, camphene, P-pinene, limonene, cineol. p-cymene, linalool and p-caryophyllene product is lighter than water and it is necessary to use suitable separators for their separation. During the distillation of eugenol, that is, after acidification, the product is heavier than water, so it is necessary to use separators for such products.

Eugenol in the form of sodium and potassium salts

In addition to the use of natural eugenol and synthetic eugenol, in the description of the invention, artificial eugenol in the form of sodium and potassium salts is indicated.

In order to prove the feasibility of the invention, the preparation of eugenol sodium salt is shown. The preparation is obtained by wet granulation technology. 40 g of acrosil is homogenized with 6.5 g of powdered anhydrous sodium carbonate (previously sieved through a 125 micron sieve). A solution of carnation oil in 96% ethyl alcohol (15 g of oil with about 70% > eugenol dissolved in 300 mL of alcohol) is added to the homogeneous mixture. The resulting mass. similar to dough, mix well in a homogenizer and then push it through a 2 mm sieve. Dry the wet granules at a temperature of up to 30°C. Drying (evaporation of alcohol) results in a granulated material with good mechanical properties. After drying, the preparation is passed through a 2 mm sieve.

In the continuation of proving the feasibility of the invention, the obtaining of the potassium salt of eugenol is shown. The preparation is obtained by wet granulation technology. 40 g of Aerosil is homogenized with 8.5 g of powdered anhydrous potassium carbonate (previously sieved through a 125 micron sieve). A solution of clove oil in 96% ethyl alcohol (15 g of oil with about 70% eugenol dissolved in 300 mL of alcohol) is added to the homogeneous mixture. Mix the resulting dough-like mass well in a homogenizer and then press it through a 2 mm sieve. Wet granules should be dried at a temperature of up to 30° C. Drying (evaporation of alcohol) results in granulated material with good mechanical properties. After drying, the preparation is passed through a 2 mm sieve.

In accordance with the intention of the invention, the preparation of sodium and potassium salts of eugenol is shown. The preparation is obtained by wet granulation technology. 40 g of Aerosil is homogenized with 3.5 g of powdered anhydrous sodium carbonate (previously sieved through a 125 micron sieve) and 4.25 g of anhydrous potassium carbonate (previously sieved through a 125 micron sieve). A solution of clove oil in 96% ethyl alcohol (15 g of oil with about 70% eugenol dissolved in 300 mL of alcohol) is added to the homogeneous mixture. Mix the resulting dough-like mass well in a homogenizer and then press it through a 2 mm sieve. Dry the wet granules at a temperature of up to 30°C. Drying (evaporation of alcohol) results in a granulated material with good mechanical properties. After drying, the preparation is passed through a 2 mm sieve.

Examples of essential oils from plants containing eugenol:

blackberries. allspice and cinnamon,

In order to improve preparations for preventive action and treatment of animal diseases caused by bacteria, fungi and parasites, very good results were obtained by using ester oils from plants containing eugenol:

1. Clove oil

The clove tree (Eugeiiia carvop/ ivllataThumb. or Carvop/ ivl/ us aromati-cusL.) grows in humid warm tropical climates. Geographical areas are Zanzibar and the Pemba Archipelago, Madagascar, Ceylon. Malaysia and Indonesia. The fruit (dried flower), shoots and leaves are used for oil production. The fruit yields 17%-18% of oil, the shoots 6%, while the leaves can be expected to yield 2-3%. The quality of clove oil is determined by its eugenol content. The highest content of eugenol is in the oil from the fruit and ranges from 85-95%). The quality of the oil obtained from young shoots is similar. The oil obtained from the leaves is of a lower quality shade, that is, with a lower eugenol content of 82-87%. Clove oil is heavier than water. The specific gravity of the oil (25° C) ranges from 1.040 to 1.069 (oils with a higher phenol content have a higher specific gravity). The optical activity (rotation) ranges from -0° 36' to -1" 40' (oils with a higher phenol content have a lower optical rotation value. The refractive index (20°C) ranges from 1.521 to 1.5391.

2. Allspice oil

The pimento tree (Pimenta ojjicinalis Lindlev, Mvrtus pimenta L. or Eitgenia pimenta D.C.) grows on the islands of the West Indies and on the islands off the coast of Central and South America. It is widely distributed in Jamaica. The largest amount of oil on the market is declared as Jamaican porcella, whether it is the oil obtained from the fruit or the leaf. The oil produced on other islands of Central and South America comes from different pimento species and differs in appearance and aroma from the product from Jamaica. Pimento fruit gives a yield of 3.3%) to 4.3%. Less oil is obtained from the leaf, and in order to obtain oil with a high phenol content, a long distillation is necessary (more than 10 hours). This type of oil is usually refined by redistillation to improve color and aroma. It is very difficult to distinguish the oil obtained from the fruit from the oil from the leaf. Allspice oil is heavier than water. The specific gravity of the oil (25° C) ranges from 1.024 to 1.055, the optical activity (rotation) ranges from -0° 32' to -5° 0'. the refractive index (20° C) ranges from 1.525 to 1.536. The phenol content (soluble part in 3% aqueous solution of sodium hydroxide) ranges from 65%) to 89%>

3. Cinnamon leaf oil

There are several types of cinnamon. From the aspect of spices and essential oil production, the most significant is Ceylon cinnamon (Ciniuimomum zevlanicum Nees). Cinnamon oil differs greatly depending on whether it is obtained from cinnamon bark or leaves. Better quality cinnamon bark (fineness 0000, in gradation 00000 for the best quality bark and 0 for the worst) yields an oil containing 62.2% to 75% cinnamic aldehyde and only 6%> to 13.2%) phenol (eugenol). The best quality cinnamon leaf oil that comes from the south of Ceylon (south of Colombo) can contain 65% to 95%) eugenol and only up to 4% cinnamaldehyde. This oil has a specific gravity (25<U>C) ranging from 1.044 to 1.065. optical activity (rotation) within the limits of -0° 15' to +2° 20' and refractive index (20° C) from 1.53 1 to 1.540.

Qualitative and quantitative rejection of eugenol

For the qualitative and quantitative determination of eugenol in commercial products (marketed as eugenol), essential oils of cloves, allspice and cinnamon, solid powder premixes with about 20% eugenol, as well as in animal feed with 0.2-0.04% eugenol (premix ratio: animal feed 1:100 to 1:500), gas chromatography with flame was used. ionizing detector GC-F1D.

Calichration straight~direct method was used to show the results

The following were taken as standard samples in this study:

Eugenol, company Merck, Catalog number 818455 CAS number 97-53-0 purity 99%. The sample was stored under nitrogen in a refrigerator at 4°C

/.vo-oklan, firm Kemika Zagreb purity for CHROMATOGRAPHY Naphthalene, firm Merck, Catalog number 820846 CAS number 91-20-3 purity 99%. As a standard solution, a standard solution of naphthalene in /.vo-octane 14 mg in 25 mL was taken. Calibration solutions of eugenol in /.vo-octane were prepared ranging from 20 to 160 mg of eugenol per liter.

Data for calibration curve ia eugenol

Determination of eugenol in essential oils. deterpenized essential oils and

commercial products can also be done in the following way:

Two samples of essential oil solutions are prepared by dissolving approximately 100 mg of oil in 25 mL of /.w-octane. 0.5 mL of each solution is diluted in a 25 mL volumetric flask with the addition of 1 mL of the internal standard. The solution thus prepared will contain about 80 mg of ether oil per liter. By comparing the surfaces of the recorded sample with the calibration surface, it is possible to calculate the content of eugenol in essential oils.

Obtaining the calihration line by the hydrodistillation method is done as follows: Make a series of dilutions of eugenol in /'vc;-octane from 200 to 1600 mg/L. 2 mL of the prepared solutions are introduced into a flask for hydrodistillation (for determining the content of essential oil according to Clavengcr) and distilled for 2 hours. The resulting solution of eugenol in /.vo-octane is dried over anhydrous sodium sulfate. 1 mL of the solution is introduced into a volumetric vessel of 10 mL, 0.4 inL of naphthalene solution is added and filled to the mark and analyzed by GC-FID.

Data for calibration line(s) eugenol

Determination of eugenol in premixes with about 20% eugenol in the form of salt is carried out

is as follows:

Approximately 0.100 g of the sample is introduced into a flask for hydrodistillation (to determine the content of essential oil according to Clavenger), 200 mL of demi-water, 1 mL of 25% H:SO4 (pH <3) and 2 mL of /.vr;-octane are added and distilled for 2 hours. The resulting solution of eugenol in w>-octane is dried over anhydrous sodium sulfate. 0.5 mL of the solution is introduced into a volumetric vessel of 100 mL, 4 mL of naphthalene solution is added and analyzed by GC-FID.

Determination of eugenol in animal feed with 0.2 to 0.04 %, eugenol in the form

of salt is done as follows:

Approximately 25 g of the fodder sample is introduced into a flask for hydrodistillation (to determine the content of essential oil according to Clavenger), and 200 mL of demi water is added. 1 mL 25% FI2SO4 (pH<3) and 2 mL /.vo-octanome and distilled for 2 hours. The resulting solution of eugenol in /.w;-octane is dried over anhydrous sodium sulfate. 0.5 mL of the solution is introduced into a volumetric vessel of 100 mL, 4 mL of naphthalene solution is added and analyzed by GC-FID.

On the basis of the methods and procedures shown above, eugenol is obtained as a colorless or pale yellow, viscous, oily substance with a characteristic smell and a spicy taste. Such eugenol has the molecular formula Cmll^O: and a molecular weight of 164.1 and a boiling point of 251° C. to 253° C. It is well soluble in ethanol, ether, chloroform and glacial acetic acid, and slightly soluble in void. In the air, it darkens and its viscosity increases. From such eugenol, a well-known method of dehydration is used to obtain a powdered veterinary preparation made of natural and synthetic eugenol and essential oils from cloves, allspice and cinnamon leaves, which is a one-component preparation that is used in the form of a powder for oral administration in the prevention and treatment of animal diseases, 1 lg of this powder contains 100 mg of eugenol. The powder is beige to cream-colored, with a strong, pleasant aromatic odor and slightly spicy taste. Aqueous suspension of this powder preparation with a concentration of 1% has a pH value of 6.2. Preserved stability lasts 2 years in a well-closed container at a temperature below 25°C in a cool and dark place.

The veterinary preparation in question is applied mixed in food in a concentration of 0.05 kg of the preparation per ton of food (0.5 g/kg of food), i.e. 0.05 g of eugenol per 1 kg of food. It should be noted that the dosing of the amount of the veterinary preparation in question is done exclusively by order of the veterinarian, who will determine the specific doses according to the type of animals, their age, weight, breeding conditions, etc.

Method of industrial or other application of the invention

Industrial or other application of eugenol, eugenol in the form of sodium and potassium salts in a matrix of hydrated aerosol and essential oils of plants containing eugenol in preparations for veterinary use is absolutely possible. Experts in the subject area can without any problems produce preparations according to the procedure given in the detailed description of the invention. Preparations can be produced in pharmaceutical facilities for the production of medicines, and even in well-equipped pharmaceutical laboratories.

Application of the invention is recommended especially in cases where it is necessary to achieve exceptional quality of meat, milk and eggs, as well as in sensitive animals that have a harder time tolerating antibiotic and sulfonamide preparations. It is especially emphasized that its application is necessary for the prevention of animals that are raised in less favorable climatic and terrain conditions.

It is emphasized that the subject invention was laboratory tested at the Faculty of Veterinary Medicine at the Department of Pharmacology and Toxicology in accordance with Article 20 of the Law on the Production and Trade of Medicines (SI. List of the SRJ No. 18/93) and the Instruction on Methods for Laboratory Testing of Medicinal Products Used in Veterinary Medicine (SI. List of the SRJ No. 34/95), which on June 16, 2004 issued an Opinion that a veterinary preparation based on eugenol, which is the subject of this invention, has pronounced antibacterial, antifungal and anticoccidial activity and is an effective coccidiocidal drug that does not exhibit any unwanted effects. According to this report, the clinical efficacy of eugenol was confirmed by testing 4,000 broilers that were one day old at the start of the trial.

Claims (7)

/. Application of natural and synthetic eugenol as an additive to animal feed, the basis of which is natural eugenol obtained from essential oils: camphor tree (Cinnamomum camphoraSieb), idjirota (Acorus calamusL), cironella from Java {Cymbopogon winterianus Jowitt), ylang ylang tree (Canangium odoratum Baill.), cananga (Cananga odorataHook.), walnut {Myristica fragransHoutt.), sassafras( Sassafras albi-dumNutt.), myrrh (Commiphora myrrhaNees), bay leaf (Laurus nobilisL.), California laurel {Umbellularia californicaNutt.), galangal root (Alpinia officinarum Hanee), apricot (Acacia farnesianaWilld.), basil {Ocimum minimumiOcimum gratissimum L.) and violets (Viola odorata L.), indicated by this, which is for separation eugenol from other accompanying components of the essential oil uses the increased acidity of the phenolic hydroxyl group, which with diluted aqueous alkali solutions builds stable water-soluble salts, which are not volatile under the influence of water vapor. 2. Application according to the request\, indicated by the fact that the basis of the feed additive in question is synthetic eugenol, i.e. 2-methoxy-4-(2-propenyl) phenol, known as 4-allyl-2-methoxyphenol, allylguaiacol (allvlguaiacol), eugenic acid (eugenic acid) and caryophyllic acid (caryophyllic acid), molecular formula C10H12O2 molecular weight 164.20. 3. Application according to requirement 2, indicated by the fact that the removal of accompanying components of natural and/or synthetic eugenol is carried out by distillation, whereby eugenol with a 3% aqueous solution of sodium hydroxide (NaOH) forms a water-soluble salt, sodium eugenolate, sufficiently stable at 100°C, so that only the accompanying components of the essential oil are distilled by steam distillation, and upon completion of the distillation, the aqueous solution is acidified. (ortho phosphoric acid) to a pH value of 4 and distilled using steam, which distills pure eugenol, and then, after separating the (lower) oily phase, it is dried and distilled under reduced pressure. 4. Application according to requirements \ and 2, indicated by the addition of eugenol in the form of sodium salt obtained by wet granulation technology, by homogenizing 65 mass/% of aerosil with 10.5 mass/% powdered anhydrous sodium carbonate, and then adding a solution of clove oil in 96% ethyl alcohol to the homogenous mixture, whereby the resulting mass is mixed in a homogenizer and then pressed sieve of 2 mm, and the resulting moist granules were dried at a temperature of up to 30°C. 5. Application according to requirements \ \2, indicated by the fact that the feed supplement contains eugenol in the form of potassium salt obtained by wet granulation technology, by homogenizing 63 mass/% of aerosil with 13.3 mass/% powdered anhydrous potassium carbonate (previously sieved through a 125 micron sieve), and then a solution of clove oil in 96%> ethyl alcohol is added to the homogenous mixture (23.7 wt/% of oil with about 70% > eugenol dissolved in 300 mL of alcohol), to mix the resulting dough-like mass well in a homogenizer and then press it through a 2 mm sieve, and then dry the obtained wet granules at a temperature of up to 30°C. 6. Application according to requirements \ \2, indicated by the well-known method of dehydration of eugenol oil to obtain a powdered one-component preparation that is used in the form of a powder in a ratio where 100 wt/% of the powder contains 10 wt/% eugenol, used for oral administration in the prevention and treatment of animal diseases. 7. Application according to claim 1, indicate at the time that the obtained eugenol is added to animal feed in a concentration of 0.05 kg/t of feed, 0.5 g/kg or 0.05 gr/kg.