CH702717A2 - Spot-on preparation. - Google Patents

Abstract

There are described repellant composition for topical application to animals, consisting of 4 to 12 wt .-% of an active ingredient, at least 80 wt .-% of a spreading agent component and 0 to 10 wt .-% excipients and / or adjuvants, wherein the active ingredient consists of one or more natural repellents of which at least 50% by weight are margosa extract and / or decanoic acid, and wherein the spreading agent component consists of at least 10% by weight of isopropyl myristate. Such compositions are characterized by good activity and long-term effect and are very well suited as spot-on formulations, in particular for use in domestic and domestic animals such as dogs or cats.

Description

Field of the invention

The invention relates to a repellant composition for topical application to animals with at least one vegetable repellent as the active ingredient.

background

Ectoparasites such as ticks, fleas, lice, hair pieces and mites are commonly found on animals such as dogs, cats, horses, rodents but also pigeons and snakes. Ectoparasites feed on their host animal and provide a constant source of irritation to the animal. In addition, they have become important as carriers of pathogens, ticks e.g. as a carrier of Lyme disease and meningitis. It is therefore desirable to minimize contact with such parasites.

[0003] There are known compositions and methods for controlling and controlling ectoparasites. Of these products, some are systemic products, i. those whose active ingredients penetrate into the bloodstream of the animals and develop the insecticidal activity as soon as the parasite sucks blood. Systemic insecticides, despite their excellent efficacy, are less desirable when other nearly equivalent, externally applicable alternatives exist. While systemic insecticides have proven to be effective against fleas, they show little or no effectiveness in controlling tick infestation. Systemic agents must be administered by injections or orally, both forms of administration that are not very popular in the animals to be treated and therefore also among the pet owners.

Also already known are topically applicable agents, e.g. those used in the spraying process, as a collar or as a spot-on. Such products are described, for example, in DE 10 117 676 A1, DE 3 531 920 A1, DE 3 529 693 A1, GB-A-2 088 212, EP 0 518 989 B1 and DE 69 126 776 T2.

In these publications are called as excipients or diluents and other auxiliaries, such as emulsifiers, adhesion promoters, spreading agents and surfactants, such as N-methylpyrrolidone xylene, toluene, cyclohexanone and alkyl glycol.

Some of these compositions, due to the active ingredients contained and / or excipients and / or adjuvants, may be used in their application, e.g. on dogs, at the point of use, cause temporary hypersensitivity of the skin, increased itching, hair loss, redness and / or blistering. These unwanted effects are known, for example, for the active ingredient permethrin and depending on the concentration and residence time of the active ingredient on the skin.

Alkyl glycol ethers have a high boiling point and a very good water solubility, as well as good miscibility with organic solvents. Their suitability as a penetration-promoting aid is controversial, as occasionally a reduction in penetration was observed. For spot-on products, the good water-solubility of the alkyl glycol ether may be a disadvantage, as if the composition is not sufficiently rapidly and completely penetrated into the skin of the animal to be treated, it will be washed off on the next contact with water. As a result, the desired duration of action is possibly greatly undercut.

WO 2005/002 339 seeks to remedy the above-mentioned disadvantages by a parasiticidal and repellant composition intended for topical application to domesticated animals and having a very high concentration of 50-90% by weight of permethrin or a stereoisomer of Permethrin contains, as well as isopropyl myristate in an amount required to reach 100 wt .-%.

Disadvantage of this composition is the extremely high permethrin concentration, especially permethrin is not completely harmless. Although permethrin has low acute toxicity to warm-blooded animals and is rapidly degraded in the body by hydrolysis, the US Environmental Protection Agency has classified permethrin as potentially carcinogenic. In addition, contact with the substance in humans can lead to itching, hair loss and allergies. For cats and fish, permethrin is toxic.

Isopropyl myristate, also known as isopropyl myristate, myristic acid 2-propyl ester, nutmeg butter derivative or - abbreviated - as IPM, is an ester of myristic (C14 monocarboxylic acid). For example, myristic acid is found in butter, palm kernel oil and coconut fat. Isopropyl myristate is an oil component used in cosmetics as a spreading and restreasing agent and as a solubilizer. Because it is a spreading agent, it ensures a good distribution of an oil or fat on the skin. It is skin-friendly and penetrates easily into the skin. Use it finds u.a. in skin creams, insect repellent oil, sunscreen oil, lipsticks u.Ä.

Commercially available naturally occurring spot-on products include, for example, as active ingredients 3.0% peppermint oil, 4.5% cinnamon oil, 4.5% lemongrass oil, 5.0% clove oil, 5.0% thyme oil, 5.0% 2-phenethylpropionate, vanilla, and 73.0% isopropyl myristate.

Margosa extract or Margosa oil is obtained from the seed of the mature flowers of the neem tree and is known as biocide. It is already offered in a high concentration of 16% by weight in spot-on products (bogacare <®>) together with citronella and clove flower oil, but nothing else is known about other ingredients. Also known is a composition containing 3% by weight of Margosa extract, 9.8% by weight of ethylbutylacetoaminopropionate and 86.95% by weight of the readily water-soluble ethyldiglycol (Bob Martin® Neem Spot-on).

The aim of the present invention was to provide an ectoparasite repellant composition with the least possible impairment of the treated mammal and low environmental toxicity combined with long-lasting activity, in particular a repellant composition with natural active ingredients.

Presentation of the invention

Surprisingly, it has been found that with certain natural active ingredients, or natural repellents, in the presence of isopropyl myristate excellent repellent effect can be achieved even at very low drug concentrations and this over a period of about 2 to 6 weeks.

Inventive repellent composition for topical application to mammals are characterized by 4 to 12 wt .-% of an active component, at least 80 wt .-% of a spreading agent component and 0 to 10 wt .-% carriers and / or excipients, wherein the Active ingredient component of one or more natural repellents consists of which at least 50 wt .-% Margosa extract and / or decanoic acid, and wherein the Spreitmittelkomponente consists of at least 10 wt .-% of isopropyl myristate.

Under a low concentration of active ingredient is a concentration of at most about 12 wt .-% understood, in particular a concentration of 4 to 12 wt .-%, preferably a concentration of 4 to 8 wt .-%, in particular a concentration of 5 bis 6% by weight.

Especially suitable active ingredients / repellents are margosa extract and / or decanoic acid. According to the invention, these make up at least 50% by weight of the total amount of active ingredient, preferably at least 70% by weight, in particular at least 90% by weight and especially preferably about 100% by weight. According to the invention, the spreading agent isopropyl myristate is used as a carrier in quantities of at least 10% by weight. The total amount of spreading agent (including isopropyl myristate is at least 80% by weight.) Preferred spreading agents are sparingly water-insoluble spreading agents, in particular isopropyl myristate.

Surprisingly, it was found that isopropyl myristate, although it also leads to the improvement of the skin penetration in addition to its function as a spreading agent, the repellent effect does not deteriorate but on the contrary reinforced and prolonged. It is believed (without the inventor wishing to be bound by theory in any way) that the surprisingly good properties of the composition on a balance between the spread, or distribution on the largest possible skin area, low water solubility and possibly the Penetration are based, it is assumed that any transport of active ingredient into the skin only in the outermost layers of skin, eg only in the epidermis, done so that due to the concentration between the skin surface and the epidermis with time again small amounts of repellent from the skin to the skin surface and unfold their effect there.

By the hydrophobic properties of the repellents and spreading agents, in particular the isopropyl myristate and optionally the penetration of a part of the composition into the skin, a washing off of the active ingredient in contact with water, e.g. in the rain, prevented, so that the long-term effect is given.

Spreaders are generally understood as meaning oily liquids which distribute themselves particularly well on the skin (see, for example, R. Keymer, Pharm. Ind., 32, 577, (1970)). Examples of spreading agents are: - Silicone oils of different viscosity Fatty acid esters such as ethyl stearate, di-n-butyl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, medium chain branched fatty acid esters with saturated fatty alcohols C16-C18, isopropyl myristate, isopropyl palmitate, caprylic / capric acid esters of saturated fatty alcohols of chain length C12-C18, isopropyl stearate, oleic acid oleate , Oleic acid ethyl ester, ethyl oleate, ethyl lactate, cetearyl isononanoates, decylolea, ethylhexyl palmitate, waxy fatty acid esters such as artificial duck short-gland fat, dibutyl phthalate, diisopropyl adipate, ester related mixtures thereof Triglycerides such as caprylic / capric triglyceride, triglyceride mixtures with natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids possibly also containing hydroxyl groups, monoglycerides of C8 / C10 fatty acids Fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oleyl alcohol and Fatty acids, e.g. Oleic acid. - Ethers, such as dicaprylyl ether, natural oils, such as sunflower oil, avocado oil.

Preferred spreading agents are sparingly water-insoluble spreading agents in water.

Particularly suitable spreading oils are next Isopropylmyristat the following: isopropyl palmitate, and triglycerides, such as caprylic / Caprinsäuretriglycerid, and Triglyceridgemische with natural fatty acids.

In addition to the active ingredient, isopropyl myristate and optionally further spreading agents, the compositions may contain other excipients and / or adjuvants, such as the homogeneous active ingredient distribution (in solution or emulsion form) promoting agents, adhesion promoters, stabilizers, film formers, conditioners, perfumes, fur shine and color agents. Such substances are known for use in cosmetics. Further carriers and / or auxiliaries are usually present in amounts of at most 10% by weight, preferably at most 5% by weight, in particular at most 2% by weight and especially preferably at most approximately 1% by weight. Preferred compositions are the active ingredient, e.g. Margosa extract or decanoic acid or a mixture of Margosa extract and decanoic acid, and the isopropyl myristate, or they additionally contain a maximum of 2 wt .-% excipients, such as perfumes, for perfumes normally an amount of 1 wt .-% is sufficient to an unpleasant To cover odor of the drug component.

Way (s) for carrying out the invention

While known spot-on products with insecticides should enter the bloodstream, or deeper skin layers of the organism to be protected, as they kill the parasites when they come into contact with the drug during stinging, the parasites become repellent products by means of the active substance evaporating from the skin via the sense of smell, or by contact of the parasite with the skin of the host animal.

In contrast to parasitic killing products, which usually contain active substances such as fipronil, permethrin, etc., which must be approved as drugs, many repellent products contain natural agents and are classified as biocides.

Known repellent agents are, for example, essential oils, e.g. Margosa extract (obtained from the neem plant) and decanoic acid (from palm oil), usually with various oils (triglycerides) as a carrier (excipiens).

In the present invention, it has now been found that when using isopropyl myristate as a carrier and spreading agent, the effectiveness and / or the duration of action of natural repellent agents, in particular the repellent agents Margosa and / or decanoic acid, can be greatly improved.

The repellant compositions for topical application to mammals according to the present invention, consist of 4 to 12 wt .-% of an active component, at least 80 wt .-% of a spreading agent component and 0 to 10 wt .-% carriers and / or excipients wherein the active ingredient component consists of one or more natural repellents, of which at least 50% by weight are margosa extract and / or decanoic acid, and wherein the spreading agent component consists of at least 10% by weight of isopropyl myristate. In preferred compositions, margosa and / or decanoic acid make up at least 70% by weight, in particular at least 90% by weight and especially preferably about 100% by weight of the repelling active ingredient.

In a preferred embodiment, the composition consists of 4 to 12 wt .-% of a natural repellents, in particular 5 to 6 wt .-%, and 0 to 5 wt .-% auxiliaries, in particular 0 to 1 wt .-% excipients , in particular about 1% by weight of perfume, and the remainder isopropyl myristate.

In particular, it has been found that isopropyl myristate (IPM) in compositions consisting of 95 wt .-% isopropyl myristate and (i) 5% Margosa or (ii) 2.5% Margosa / 2.5% decanoic acid or (iii) 5% decanoic acid or from 94% by weight of isopropyl myristate and (i) 5% margosa or (ii) 2.5% margosa / 2.5% decanoic acid or (iii) 5% decanoic acid and 1% by weight of perfume gives excellent activity.

The active ingredient component, in addition Margosa extract and / or decanoic also garlic extract, Eucalyptus citriodora, tomato extract, essential oils such as peppermint, cedar wood extract, citronella oil, extracts of Citrus hystrix, extracts of Cymbopogon winterianus, extracts of Ocimum americanum and mixtures thereof.

Preferred mixtures of Margosa extract and decanoic acid are mixtures in the ratio 30:70 to 70:30, in particular in the ratio 40:60 to 60:40, especially preferably about 50:50.

Such compositions are basically suitable for topical application to all mammals, including humans. The application is preferred as a spot-on formulation.

Preferred domestic and domestic animals for spot-on application are dog and cat, but also rodents, guinea pigs, pigeons and snakes.

The novel compositions can be prepared by simply mixing together the ingredients.

Preferably, the compositions for dogs and cats are dispensed in unit quantities of 1 ml to 2 ml in ampoules. Such ampoules are known for spot-on products.

Alternatively, the compositions may be filled into aerosol cans, e.g. for the treatment of large animals, for example of horses.

In general, isopropyl myristate can also be used to improve the efficacy of topically applied compositions containing repellent agents that do not fall within the preferred limits of the above-mentioned compositions. While an improvement in the effect can be achieved, a lower effect is expected than with a composition according to the invention.

Examples:

Examinated formulations:

[0039] <Tb> Ingredient <sep> Formulation <sep> Formulation <sep> Formulation <sep> Formulation <Tb> <sep> 1 <sep> 2 <sep> 3 <sep> 4 <Tb> isopropyl <sep> 94 <sep> 94 <sep> 94 <sep> 94 <Tb> capric / caprylic <sep> 0 <sep> 0 <sep> 0 <sep> 5 <Tb> triglyceride * <sep> <sep> <sep> <sep> <tb> Margosa Extract <sep> 2,5 <sep> 5 <sep> 0 <sep> 0 <Tb> decanoic <sep> 2.5 <sep> 0 <sep> 5 <sep> 0 <tb> fragrance <sep> 1 <sep> 1 <sep> 1 <sep> 1 * Myritol 318 from Cognis

Effect on cats

As animals for the study, cats were chosen because of these side effects appear better than for example in dogs.

Selection of the experimental animals

The cats chosen for the study are animals that were acquired from a shelter and the circle of acquaintances of the laboratory staff. In order to keep the stress of the animals as low as possible, they remained under the care of their owners for the entire duration of the test and were brought to the laboratory only for the experiments.

Application of the product

Each 2 ml of the test product were applied with a calibrated plastic pipette directly to the skin of the cats in a line from the back of the head to the tail root. To ensure that the product is applied directly to the skin, not to the coat, the coat of the cats was combed apart directly before or during application along that line.

experimental arrangement

The experimental animals were examined at the beginning of the experiment on the type and number of infestations and treated according to its documentation, as described above with the test product. Thereafter, all animals were released back to their original areas and examined about every five days for existing parasites to re-infestation - by nature of fleas - was present. The 30 subjects were tested in each of the months of July to November 2009. The time to complete freedom of infestation is called Austreibungszeit; the time from the first established infestation freedom to the first infestation is called the protection period. At the same time animals were tested with agents without active ingredients as a control to measure the infestation pressure under the test conditions.

Recipe 1

[0044] <Tb> T [Days] <sep> infestation Cat 1 <sep> infestation Cat 2 <sep> infestation Cat 3 <sep> infestation Cat 4 infestation Cat 5 <tb> 0 <sep> 12 F <sep> 6 F / 2 Z <sep> 8 F / 3 Z <sep> 2 F / 6 Z <sep> 7 F / 2 Z <tb> 5 <sep> - <sep> - <sep> 1 F <sep> - <sep> - <Tb> 10 <sep> - <sep> - <sep> - <sep> - <sep> - <Tb> 15 <sep> - <sep> - <sep> - <sep> - <sep> - <Tb> 21 <sep> - <sep> - <sep> - <sep> - <sep> - <tb> 25 <sep> 1 F <sep> - <sep> 1 Z <sep> - <sep> - <Tb> 30 <sep> - <sep> - <sep> - <sep> - <sep> - <tb> 35 <sep> 4 F / 1 Z <sep> 2 F <sep> 3 F / 1 Z <sep> 5 F <sep> 4 Z

Recipe 2

[0045] <Tb> T [Days] <sep> infestation Cat 6 <sep> infestation Cat 7 <sep> infestation Cat 8 <sep> infestation Cat 9 <sep> infestation Cat 10 <tb> 0 <sep> 4 F / 6 Z <sep> 12F / 2 Z <sep> 8 F / 2 Z <sep> 2 F / 3 Z <sep> 15 F <tb> 5 <sep> - <sep> - <sep> 2 F <sep> - <sep> - <tb> 10 <sep> - <sep> 2 F <sep> - <sep> - <sep> 2 F <tb> 15 <sep> 2 Z <sep> - <sep> - <sep> - <sep> - <tb> 21 <sep> - <sep> - <sep> - <sep> 1 F <sep> - <tb> 25 <sep> - <sep> - <sep> 1 Z <sep> - <sep> - <tb> 30 <sep> - <sep> - <sep> 1 F <sep> - <sep> - <tb> 35 <sep> 2 F / 3 Z <sep> 3 Z <sep> 3 F / 1 Z <sep> 5 F <sep> 8 F / 4Z

Recipe 3

[0046] <Tb> T [Days] <sep> infestation Cat 11 <sep> Infestation Cat 12 <sep> infestation Cat 13 <sep> infestation Cat 14 infestation Cat 15 <tb> 0 <sep> 12 F <sep> 6 F / 2 Z <sep> 8 F / 3 Z <sep> 2 F / 6 Z <sep> 7 F / 2Z <tb> 5 <sep> - <sep> - <sep> 2 F <sep> - <sep> - <Tb> 10 <sep> - <sep> - <sep> - <sep> - <sep> - <Tb> 15 <sep> - <sep> - <sep> - <sep> - <sep> 1Z <Tb> 21 <sep> - <sep> - <sep> - <sep> - <sep> - <tb> 25 <sep> 1 F <sep> - <sep> 1 Z <sep> - <sep> - <Tb> 30 <sep> - <sep> - <sep> - <sep> - <sep> - <tb> 35 <sep> 4 F / 1 Z <sep> 2 F <sep> 3 F / 1 Z <sep> 5 F <sep> 2F / 4Z

Recipe 4

[0047] <Tb> T [Days] <sep> infestation Cat 16 <sep> infestation Cat 17 <sep> infestation Cat 18 <tb> 0 <sep> 12 F <sep> 8 F <sep> 6 F <tb> 5 <sep> 8 F / 3 Z <sep> 8 F / 3 Z <sep> 10 F / 2 Z <tb> 10 <sep> 14 F / 2 Z <sep> 14 F / 2 Z <sep> 5 F / 2 Z <tb> 15 <sep> 23 F / 3 Z <sep> 23 F / 3 Z <sep> 13 F / 1 Z <tb> 21 <sep> 20 F / 1 Z <sep> 20 F / 1 Z <sep> 14F / 1 Z <tb> 25 <sep> 1 F <sep> 1 F <sep> 9 F <tb> 30 <sep> 13 F <sep> 13 F <sep> 6 F <tb> 35 <sep> 8 F / 1 Z <sep> 8 F / 1 Z <sep> 8 F / 1 Explanations: t: Time after order of the product in days t = 0 days: Determination of the infestation immediately before application of the respective recipe F: fleas; Z: ticks

None of the cats experienced any side effects.

While preferred embodiments of the invention have been described in the present application, it is to be understood that the invention is not limited to these and may be practiced otherwise within the scope of the following claims.

Claims (10)

1. A repellant composition for topical application to animals, consisting of 4 to 12 wt .-% of an active ingredient, at least 80 wt .-% of a Spreitmittelkomponente and 0 to 10 wt .-% carriers and / or excipients, wherein the active ingredient of one or a plurality of natural repellents, of which at least 50% by weight are margosa extract and / or decanoic acid, and wherein the spreading agent component consists of at least 10% by weight of isopropyl myristate. 2. A composition according to claim 1, characterized in that the spreitmittelkomponente isopro-pylpalmitat and / or triglycerides, such as caprylic / Caprinsäuretriglycerid, and / or triglyceride containing natural fatty acids. 3. A composition according to claim 1 or 2, characterized in that the Spreitmittelkomponente consists of at least 90 wt .-%, in particular about 100 wt .-% of isopropyl myristate. 4. A composition according to any one of the preceding claims, characterized in that it comprises from 4 to 12 wt .-% active ingredient, 0 to 5 wt .-% excipients, in particular 0 to 1 wt .-% excipients, in particular about 1 wt. % Perfume, and the rest is isopropyl myristate. 5. A composition according to any one of the preceding claims, characterized in that in the active ingredient in addition to margosa extract and decanoic acid contained natural repellents are selected from the group consisting of essential oils and mixtures of essential oils. 6. A composition according to any one of the preceding claims, characterized in that the active ingredient component is selected from the group consisting of Margosa extract, decanoic acid, and a mixture of Margosa extract and decanoic acid in the ratio of 30: 70 to 70: 30, in particular in proportion 40: 60 to 60: 40, especially preferably in the ratio of about 50: 50. 7. A composition according to any one of the preceding claims, characterized in that the active ingredient component in amounts of 4 to 8 wt .-%, in particular from 5 to 6 wt% is present. Composition according to any one of the preceding claims, characterized in that the animals are domestic animals and / or pets, in particular dogs and / or cats and / or horses, especially dogs and / or cats. Composition according to any one of the preceding claims, characterized in that it is a spot-on formulation. 10. Use of isopropyl myristate for improving the efficacy of topically applied compositions containing repellent agents.