RO133704A2 - Composition of veterinary use, based on natural active principles, for treating external otitis and process for preparing the same - Google Patents

Abstract

The invention relates to a process for preparing a composition to be used as adjuvant in the treatment of external otitis of bacterial and parasitic etiology in dogs, cats and rabbits. According to the invention, the process consists in preparing a tincture from a mixture of 10...30 kg of plants comprising 5...25% ivy (Hedera helix), St. John's wort (Hypericum perforatum), milfoil (Achillea millefolium), comfrey (Symphytum officinale), black poplar (Populus nigra) buds, sage (Salvia officinalis), marigold (Calendula officinalis), plantain (Plantago major) and burdock (Arctium lappa), respectively, in 80...100 l of propylene glycol and 20...40 l of water, 5...11% of the tincture being further incorporated in a mixture based on glycerin, salicylic acid, propylene glycol, dimethyl carbinol, extract of Dalmatian pellitory flowers, with homogenization for 10 min, to result in a composition of veterinary use exhibiting reduced toxicity.

Description

iiiiiiiîiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii

Veterinary composition based on natural active principles for the treatment of external otitis and process for its preparation

The invention relates to a composition used as an adjuvant and to a process for its preparation, usable in dogs, cats and rabbits, for the treatment of external otitis with bacterial and parasitic etiology, and is an improvement of the invention in the Patent Application A / 00063 / 01/02/2018.

There are known different compositions used as adjuvants, with a wide range of action. Thus, the IVERMITE OTIC product of Farmavet S.A. from Romania contains 0.03 mg ivermectin and excipients up to 1 g: 2 mg methyl parahydroxybenzoate, 1 mg propyl parahydroxybenzoate and glycerin + propylene glycol. IVER-MITE OTIC solution contains as active substance ivermectin, an antiparasitic substance with a scabicidal effect that acts by increasing the permeability of the cell membrane to chlorine ions by hyperpolarizing the nerve or muscle cells, causing paralysis and death of the parasite; it also determines the secretion of gamma aminobutyric acid (GABA) at the nerve synapses of the parasite, thus disrupting the nerve impulse. Ivermectin is an antiparasitic substance in the macrocyclic lactone class, isolated from the product obtained by fermentation of an actinomycete called Streptomyces avermitilis. Instill 2-5 drops of product and gently massage the base of the ear, thus favoring direct drug contact - ectoparasites. After a few minutes the excess product is removed by light buffering with hydrophilic wool. [Http://www.pasteur.ro/produse/iver-mite-otic/]

Another well-known product, MITEX of the company RichterPharma AG in Austria contains 23 mg miconazole nitrate 5 mg prednisolone acetate, 5500 IU polymyxin B sulfate and as an excipient up to 1 g benzyl benzoate. It is a white suspension, effective in the treatment of external otitis due to sensitive fungi, yeasts and bacteria in dogs and cats. [Www.biotur.ro/vet/caine/otice/mitex-picaturi]

Known compositions have the following disadvantages:

1. Although it is generally well tolerated, ivermectin can cause unpleasant side effects if the dose is very high. Symptoms of drug overdose or toxicity include: tremor, uncertain gait, hindering, temporary blindness, dilated pupils, disorientation, weakness, lack of appetite, vomiting, heavy salivation, heavy or accelerated breathing, and generally appear at 12 hours after administration .

2. Not used in the treatment of parasites in hypersensitive animals. Ivermectin is not given to chicks under 2 months of age, to convalescent or weakened animals. It is not used in the Collie breed and its artichokes (due to the potential toxic side effects), the breed being very sensitive.

3. It should not be used in case of hypersensitivity to the active substance or to any of the excipients.

4. Not used in the case of perforated tympanic membrane due to possible ototoxic effects of the polymyxin B sulfate antibiotic content.

5. In case of prolonged application, especially in cats, a possible increase in sensitivity to the product should be considered.

6. The active substances in its composition are synthetic substances.

7. Need to work with toxic solvents when inhaled.

The technical problem solved by the invention consists in widening the range of adjuvants by using active components obtained from plants and not only active synthetic components, which have a low toxicity both to the animal and to the operator.

The composition, according to the invention, removes the disadvantages of the more cube by that. .. * J THE OFFICE OE THE PEHERUINVENTIONS IN MAHCI in propylene glycol and contains an extract of:

- Ivy (Hedera helix);

- Stingrays (Hypericum perforatum);

- The tail of the rat (Achillea millefolium);

- Tătăneasă (Symphytum officinale);

- Poplar buds (Populus nigra);

- Garden shed (Salvia officinalis);

Patent application

Filing date &

Go to 2018 00307

04/05/2018

- Yellowfin (Calendula officinalis);

- Platagina (Plantago major);

- Brusture (Arctium lappa).

and the solvent used is propylene glycol C3H8O2. Tincture obtained from the previously described plant mixture is transformed into suspension by mixing with a solution consisting of:

- Glycerin CH ₂ OHCHOHCH ₂ OH;

- C ₆ H ₄ (OH) COOH salicylic acid;

- Propylene glycol (Propane 1.2 - Diol) CaHsCh, also known as El520;

- Flowers of wild chrysanthemum (Tanacetum cynerariifolium) extract 50%;

- Polyquaternium - 7 (CsHjâClNjn ^ HsNOjm;

- Isopropyl alcohol (isopropanol) C3H7OH.

Glycerin CH ₂ OHCHOHCH ₂ OH, the simplest trihydroxyl alcohol, is used as an emollient and achieves softening of the skin, giving better adjuvant adhesion. Vegetable glycerin is well tolerated by the skin and has an exceptional property, moisturizing the skin with its own reserves, which it brings from the tissues. Basically, it "squeezes" the excess water and uses it where it is needed.

Salicylic acid C6H ₄ (OH) COOH, an aromatic hydroxyacid, precursor of acetylsalicylic acid, is a colorless, crystalline compound, which has bactericidal, antipyretic and antiseptic properties, being used to relieve pain and reduce fever. Its role in mixing is that of antifungal and soothing of the skin, the active substances being able to act more effectively.

Propylene glycol C3HsO ₂ is used as a support agent, antifoam, emulsifier with bactericidal action, having a special ability to retain, absorb moisture, soften the skin, reduce swelling.

What makes the wild chrysanthemum special is its flowers which contain a substance called pyrethrine, a powerful insecticide. Completely harmless to humans and animals, pyrethrum obtained from wild chrysanthemum flowers - Tanacetum cinerariifolium causes insect death by paralysis.

Polyquaternium - 7 (CgHiClNjn ^ HsNOjm is the co-polymer of acrylamide with a quaternary nitrogen salt (dialyldimethylazole chloride), being a clear, colorless to yellow liquid that is used as an antistatic, forming a barrier in the hair. or inhibits the accumulation of static electricity and dries to form a thin coating absorbed on the hair shaft, inhibiting the hair's ability to absorb moisture.

C3H7OH isopropyl alcohol is used as a solvent, being both antiseptic and astringent. It is a bitter, transparent and colorless bitter aromatic liquid that can be mixed with water, alcohol and other solvents. Because it is both antiseptic and astringent at the same time, and because it dries very quickly, isopropyl alcohol can be used to clean and stop bleeding in the case of minor wounds. Cleaning the area around a wound with this alcohol helps to degrease and better grip. Antiseptics, such as isopropyl alcohol, rapidly kill microorganisms that live on the surface of the skin.

The composition according to the invention has the following advantages:

1. The active substances in its composition are strictly of natural origin (from plants).

2. Prepare cold.

3. Does not require, in preparation, toxic substances.

4. Has no contraindications.

5. Low toxicity in both animal and operator.

The composition according to the invention contains a tincture (recipe a) obtained from an amount of 10 30 kg of plant mixture, 20 + 40 1 water and 80 + 100 1 propylene glycol, the plant mixture being compound (recipe b) - for example - from the ivy (Hedera helix) with Stingrays (Hypericum perforatum), with the tail of the rat (Achillea millefolium), with the root of Tătăneasă (Symphytum officinale), with poplar buds (Populus nigra), with garden jelly (Salvia officinalis), with Yellow (Calendula officinalis), with Pătlagina (Plantago major), with Brusture (Arctium lappa). The mixture of plants presents a percentage of the plants constifu ^^^ varies in wide limits, from 5% to 25% for each plant. Tincture obtained / remade a) suspends by incorporating it into a suspension recipe (recipe c), composition 8 1 - 10 1 Glycerin CH ₂ OHCHOHCH ₂ OH, 50 g - SOOgnAgidț ^ Ati a 2018 00307

04/05/2018

C ₆ H ₄ (OH) COOH, 0.5 - 2 1 Propylene glycol (Propane 1.2 - Diol) C ₃ H ₈ O ₂ , 0.5 - 3 1 C3H7OH isopropyl alcohol, 20 + 150 ml wild chrysanthemum flower extract (Tanacetum cynerariifolium), 0.5 + 2 1 tincture (recipe a), Polyquatemiu - 7 (C ₈ Hi6ClN) _n (C ₃ H5NO) m. The effect of the adjuvant, according to the invention, is greatly enhanced over other adjuvants due to the presence of plant extracts, each plant having a specific pharmacodynamic action:

- Ivy has topical action in ulcerations and analgesic in neurites, cellulites and cellulalgias. It has antibiotic action (especially on gram-positive germs) and fungicide (compared to Candida albicans and several strains of dermatophytes), it has anti-inflammatory, anti-edema and insecticidal action, indicating its use as an extract, as the fresh plant is a strong irritant. dermal (used only on abscesses or boils for maturation in the form of compresses).

- St John's wort has, among other things, due to volatile oil, hypericin and tannin, antiseptic, astringent, anti-hemorrhagic (hemostatic), anti-inflammatory and healing action, as well as the action of the vitamin P, which is caused by the glycoside in the rattlesnake carbohydrate chain consisting of galactose, giving it a better solubility, diffusion and permeability, which also explains its vasodilatory action. It protects the injured tissues, without stopping the suppuration, the secretion, and as an antiseptic it has antibacterial, antiviral and antifungal action, being indicated in external use, as a scar and disinfectant in purulent wounds and burns, on wounds and burns that are hard to cure, on eczema.

- The tail of the mouse, due to the components of the volatile oil, especially the camazulena, has anti-inflammatory, slightly antiseptic and radiation-protective, epithelizing, ethereal and alcoholic extracts of leaves and flowers having antibiotic action and due to the bitter substance, achilles time-shortening of the blood, while reducing congestion, dries the secretion and has disinfectant and soothing properties.

- Tătăneasa, due to its components, especially allantoin, has hemostatic, anti-inflammatory, astringent and healing properties.

- Poplar buds have anti-inflammatory, antiseptic, healing, astringent and weak analgesic properties, due to the phenolic glycosides also having antibacterial and antifungal properties.

- The garden jelly has anti-inflammatory, healing and slightly astringent properties, being local hemostatic and having antibacterial and antifungal properties.

- The yellows, due to their components, have anti-inflammatory, anticatalatal, antiseptic and healing properties, the extracts inhibit the development of golden staphylococcus, Echerichia coli and Candida albicans and also have antiviral and anti-trichomoniasis activity, support the skin, regenerate the epidermis.

- Padlagina, due to mucilages, plantoses and some hydrolysis products, has emollient properties, due to tannins and aucuboside, it has antiseptic, anti-inflammatory, astringent, hemostatic, scarring, anti-cataract and anti-pruritic properties, while the mucilage from the protruding enzyme, to macerate the skin, the open wound being sterilized by the polyphenolic substances, and the carotenoids, phytosterols and fatty acids with healing action contribute to the recovery of the diseased tissue, the damaged and the fatty oils in the plant protect the wound from the ultraviolet radiation.

- The burns have antibacterial properties, especially compared to the gram-positive, antiviral and have a regenerating effect on the epidermis.

The invention also relates to a process for preparing the composition. The raw material for obtaining the extract (tincture) is obtained by harvesting certain parts of the component plants, as follows:

- Ivy: The raw material used to obtain the ivy extract is formed from the young leaves on the sterile 3-5 lobed branches, long petioles, glabrous, glossy, dark green on the face, with a palpable nerve, collected all year round, without characteristic odor, slightly astringent taste, bitter; it contains saponozides: hederins, hederacozide A, which by hydrolysis gives glucose, arabinose and hederagenin, a pentacyclic triterpene ^ t, sheep ^ <also contains polyphenolic compounds: rutoside, rutinoside; chlorogenic acid ^> bafeiq ^ / <scopoline, sugars, mineral salts, beta-carotene, alpha-tocopherols and high-stress substances ^ tj ^^ v ^

- Stinging: The raw material used to obtain the extract of the stinging esjâfoi ^ n ^ t ^ A'7 from the embossed or flowered terminal parts of the plant, provided that the part / edge ^ Rjâi ^ Λ · of 2018 00307

04/05/2018 Thickness of the stem should not exceed 2 mm in diameter, the length of the parts that are harvested until July is 20-30 cm and is provided with cylindrical branches, with two longitudinal edges, green or reddish-green. , with elliptical leaves, opposite, glabrous, green, with small black dots on the entire edge and with numerous punctuations (glands) on the entire surface of the tongue, which looked through transparency, it looks perforated, and the flowers, arranged in tufts, have the calyx and corolla pentameres , sepals lanceolate, golden yellow petals with black spots, having characteristic balsamic odor, aromatic-bitter taste, resinous and astringent; the dry plant contains 0.05-0.10% volatile oil in the aerial parts and 0.40-0.50% in the flowers, the volatile oil containing alpha-pinen and hexagonal carbides, mineral salts, also contains polyphenolic derivatives: a flavonoid - hyperoside (galactoside of quercetol), rutoside, cvercetol, caffeic and chlorogenic acid and also contains catechin tannin up to 12%, a coloring substance - Hypericum red or hypericin - which has a strong red fluorescence in ultraviolet light, being a red fluorescence, of naphthodiantrone, choline, carotenoids, saponins, ascorbic, nicotinic and valerianic acid.

- The tail of the mouse: The raw material used to obtain the extract of the tail of the mouse is composed of flowering inflorescences completely collected at noon, in dry weather, in August and September, that is, the upper part of the plant, approx. 30 - 40 cm or flowers collected with a 3-4 cm stem from the species Achillea Millefolium L., Achillea collina Beker, Achillea pannonica Scheele, Achillea crithmifolia W. et K. and Achillea stricta Sch., Which are often harvested together they can be easily recognized by the feathery leaves, sectioned, glabrous or hairy, with smooth, evenly distributed lacunae, the narrow or linear lanceolate ones, and the numerous, elongate-ovoid anthers, with green-yellow involute leaflets sometimes narrow and brown in margin. while the marginal flowers are white, sometimes rosy, with obovate leagues, having a slight aromatic odor, bitter taste, slightly salty, astringent; the aerial parts of the plant (harvested during flowering and dried) contain 0.10-0.40% volatile oil, and the inflorescences up to 0.50%, volatile oil containing 8-10% monocyclic triterpenic compounds, as well as bicyclic triterpenes, such as: d-alpha-pinene, 1-bomeol, triion, caryophyllene, other sesquiterpenes and sesquiterpenic alcohols, salicylic acid, formic, acetic, isovalerian and camazulene, the content of camazulen varying between 0.01 and 0.10% in inflorescences and in oil volatile between 20 and 30%, depending on the species, the time of flowering, the individual character, the way of drying, storage, etc., besides the volatile oil, the aerial parts still containing a bitter substance of glyco-alkaloid nature - achilein, tannin (approx. 3 %), aconitic acid, asparagine, choline, ascorbic acid (about 0.30%) in the dried leaves, fatty oil (about 2%) consisting of linoleic, oleic, myristic, palmitic and glyceride acids of these acids, free ceryl alcohol and in the form of acetate, res ring (about 0.6%), a benzaldehyde hydrochloride glycoside, etc.

- Tăneasă: The raw material used to obtain the tăneasa extract consists of rhizomes with whole roots or root fragments 10-15 cm long, with a blackish outer surface, with longitudinal striations, on a white or yellowish-white interior, with a net fracture, not smooth , without characteristic odor, weak mucilaginous taste, harvested in March and May, rhizomes and roots containing 0.6-0.8% allantoin, mucilages, glycosidic substance: consolidin and consolicin, tannin, choline, asparagine, gumirezine, sugars , starch, small amounts of alkaloids: symphito-cinoglosin, coniferin, mineral substances, etc.

- Poplar buds: The raw material used to obtain the black poplar extract is composed of ovoid buds, uneven, covered with bracts, sharp at the tip, glossy, 1-2 (3) cm long and 4-6 mm thick, harvested by at the end of February until the beginning of April, being resinous inside, light brown to brown in color, with a pleasant, resinous, balsamic odor, taste of bitter aroma and containing phenolic glycosides: salicin and poplin; 0.5% volatile oil consisting of betulin, alpha-, beta- and gamma-betulenol, d-humulene, alpha-carophylene, flavonic compounds: chrysine and tectocrizin, ca. 1.5% tannins, resins, fatty oil, malic and gallic acid, saponins, mannitol, etc.

- Garden jelly: The raw material used to obtain the garden jelly extract is made of elongated ovate or lanceolate leaves, less elliptical, 2-8 cm long and 0.5-3 cm wide, with a rounded or tapered base, less easily cordiform, harvested-upstream or immediately after flowering, at the base of the leaves sometimes having two small lobes arc a jfotuâw ^. and the edge of the tongue is finely toothed, sometimes almost entire, while the middle and middle fruits are petiolate, and the upper ones are sessile, cross-linked and feathered.

O * W

to 2018 00307

04/05/2018 lower and on the prominent parts of the upper part the leaves are often whitish hairy with fine, multicellular hairs, which give them a general green-silver appearance, the odor being characteristic, the aromatic taste bitter; the aerial parts of the plant contain 0.20-0.60% volatile oil, and the leaves harvested at the beginning of flowering 1-2%, the volatile oil being composed of thyme, salvinol, absintol, alpha- or beta-pinene, linalyl acetate, camphor, borneol, bornyl acetate, cineole, sescviterpene, etc. and in addition to volatile oil, the leaves also contain tannin, ursolic acid, oleanolic acid, a bitter principle - picrosalvine, phytosterols, fumaric acids, chlorogenic, nicotinic, caffeine; saponozides, resins and oleo-resins, estrogen, vitamin Bl and C, potassium nitrate, etc.

- The yolks: The raw material used to obtain the yolk extract is made from flowers with the receptacle, consisting of dried yellow-orange colorings surrounded by green bracts, without the stalk, harvested only on sunny days from June to October, with odor. weak aroma, bitter salt taste, yellowish flowers with triterpenic saponozides containing oleanolic glucuronyl derivatives: carotenoids including lycopine, alpha- and beta-carotene, neolicopin A, rubixantin, lutein, xanthophyll, violaxanthin, flavoxanthin, flavoxanthin etc., as well as some polyines; flavonoids and flavonic glycosides: isoramnetin-3-ramnoglycosides, rutinozides and cvercetol derivatives, volatile oil (ca. 0.02%), bitter substances with indefinite structure, gumirezine, mucilages, cholesteryl esters, palmaric acids, lauric acids, lauric acids, lauric acids, Vitamin C, malic acid, protein, etc.

- Patina: The raw material used to obtain the patina extract is made up of leaves of elongated-lanceolate form, sharp at the tip, with thin petiole and long, with ribs more visible on the underside, approx. 20 cm wide and 4 cm wide, with entire or slightly denticulate margins, hairy to glabrescent with usually hairy woolly petiole, harvested before or during flowering, having a specific green color, with brown spots resulting from drying to a maximum of 10% , without specific odor, with a bitter sour taste, the aerial parts of the plant containing mucilages consisting mainly of xylose, polyuronic acid, pentoses etc., aucubin, or aucubozide which by hydrolysis gives aucubigenin and a glucose molecule, a triose, plantose, tannin , glycosides, saponins, sugars, volatile oil, resins, protein substances, caritenoids, phylloquinone, vitamins A, C and K, antibiotics etc.

- Burrows: The raw material used to obtain the bump extract is made up of roots from plants of 1-2 years old, whole or sectioned, in approx. 10-15 cm, spongy, whitish, harvested in March, April, May, October, November, with a slight characteristic odor, taste of mucilaginous sweetness, then bitter, the roots of the plant containing large quantities of inulin (about 40%), palmitic acid, stearic acid, sitosterol and stigmasterol, small amounts of volatile oil (about 0.10%), B vitamins, caffeic acid, antibiotics with an as yet unpolished structure, etc.

The plants are chopped into a mill with a screen granulation of 0.5 - 2 cm, after which the plant mixture is weighed and elaborated (recipe b), the homogenization of the plant mixture was done in the homogenizer for 20 minutes, then propylene glycol and water are added. (recipe a) at room temperature in a dark-colored plastic container in which a homogenization is performed again with a hand-mixer, then the container is hermetically sealed and the mixture is left to macerate for 2-3 weeks in the protected container. of sunlight, mixing daily and obtaining the tincture after the expiration of the mentioned period by mechanical pressing of the mixture, the impurities being removed by sedimentation 2-3 days and filtering, then measuring the quantities needed for the c suspension recipe and dissolving the acid salicylic in propylene glycol for 5 minutes, after which the two mixtures are introduced into a mixer under slow stirring, add the remaining ingredients and mix for 10 minutes.

Claims (10)

CLAIM 1. Composition for veterinary use based on natural active principles for the treatment of otitis externa, obtained from a tincture on plants: ivy, rattlesnake, tail of the mouse, heather, poplar buds, sage, yellows, patina, brust, characterized by the fact that Glycerin also contains CH2OHCHOHCH2OH, CâHXOHjCOOH salicylic acid, Propylene glycol (Propane 1.2 - Diol) C3H8O2, also known as El520, wild chrysanthemum flower extract (Tanacetum cynerariifoliern), Phnomacropyrum Veterinary composition based on natural active principles for the treatment of external otitis, according to claim 1, characterized in that the percentage of glycerin in suspension is from 56% to 84%. Veterinary composition based on natural active principles for the treatment of external otitis, according to claim 1, characterized in that the percentage of Tincture in suspension is from 5% to 11%. 4. A composition for veterinary use based on natural active principles for the treatment of external otitis, according to claim 1, characterized in that the percentage of salicylic acid in suspension is from 0.5% to 3%. 5. Composition for veterinary use based on natural active principles for the treatment of external otitis, according to claim 1, characterized in that the percentage of Propylene glycol in suspension is from 5% to 11%. 6. Composition for veterinary use based on natural active principles for the treatment of external otitis, according to claim 1, characterized in that the percentage of suspension of wild chrysanthemum flowers in suspension is from 0.3% to 1%. 7. Composition for veterinary use based on natural active principles for the treatment of external otitis, according to claim 1, characterized in that the percentage of suspended Poliquaternium - 7 is from 0.2% to 0.5%. Veterinary composition based on natural active principles for the treatment of external otitis, according to claim 1, characterized in that the percentage of suspended isopropyl alcohol is from 5% to 17.5%. 9. Composition for veterinary use based on natural active principles for the treatment of external otitis, according to claims 1, 2, 3, 4, 5, 6, 7 and 8, characterized in that it comes in the form of a suspension applicable directly to the skin. 10. Process for the preparation of a composition for veterinary use based on natural active principles for the treatment of external otitis, characterized in that the elaboration of the suspension takes place by dissolving salicylic acid in propylene glycol, followed by the addition of the tincture obtained from the plants, the addition of glycerin, wild chrysanthemum extract, polycatemate-7 and isopropyl alcohol, all of the composition supporting a homogenization.