WO2013041696A1

WO2013041696A1 - Stimulating and invigorating nasal spray and nasal drop

Info

Publication number: WO2013041696A1
Application number: PCT/EP2012/068688
Authority: WO
Inventors: Hyeck-Hee Lee; Ute Steinfeld; Frank Holzer
Original assignee: F. Holzer Gmbh
Priority date: 2011-09-21
Filing date: 2012-09-21
Publication date: 2013-03-28
Also published as: DE102011114094A8; DE102011114094A1

Abstract

The invention relates to the use of a composition containing at least one ethereal oil and at least one simulating substance for nasal administration. The composition is introduced into the nose, in particular formulated as a nasal spray or nasal drop, but is also suitable for inhalation.

Description

Stimulating and invigorating nasal spray and

nose drops

The present invention relates to the use of a composition containing at least one essential oil and at least one stimulating substance for nasal administration. The composition is introduced into the nose, in particular it is formulated as a nasal spray or nose drops, but also suitable for inhalation.

Compositions comprising essential oils are known in the art.

JP 06040906 A relates to a sleep suppression composition comprising essential oils; this composition may be nasal, for example in the form of a spray.

EP 1 346 726 A1 relates to a sympathetic nervous system stimulating fragrance composition containing certain essential oils. This composition is used topically.

The object of the present invention is to provide a composition which has a particularly high stimulating effect.

This object is achieved by the use of a specific composition according to claim 1, a method for stimulation and / or activation of the sympathetic nervous system with the features of claim 15 and a nasal spray or the nose drops with the features of claims 16 and 17. The respective dependent claims are advantageous developments. According to the invention, the use of a composition is specified, wherein the composition contains at least one essential oil and at least one stimulating substance. In addition, the composition contains at least one wound-healing-promoting substance selected from the group consisting of hyaluronic acid, dexpanthenol and chondroitinic acid. According to the invention, the composition is administered nasally and / or inhaled.

The present composition combines the following properties:

-> stimulating, alerting, concentrating and enhancing nasal spray that reduces the signs of physical and mental fatigue,

with at the same time very good mucous membrane compatibility,

-> As well as a very good durability or a very good protection of the essential oils from evaporation during storage z. Eg in a multi-dose system (nasal spray).

According to the invention, a stimulating substance is understood as meaning a substance or a mixture of substances which excites the sympathetic nervous system of a human or an animal, wherein, for example, there is an increase in cardiac activity, blood pressure, perfusion, and skeletal muscle tone, glycolysis, and metabolism. By stimulating the sympathetic, overall an increase in performance of the organism (ergotrophy) is achieved. In addition, the lung function can also be increased.

The administration of a stimulating substance, such as caffeine on the nasal route shows, in contrast to oral intake, a much faster effect. This can be explained by the physiological mechanism of action in the brain: the stimulating effect of caffeine results primarily from the binding to adenosine receptors of the Ai and A _2A type. This results in a disinhibition of certain regions in the CNS.

When administered via the nasal mucosa, the caffeine probably passes directly into the brain via small blood vessels along the olfactory nerve, so that a very fast effect is achieved after just a few minutes, about 5-15 minutes. For example, the caffeine content in cola is about 6-25 mg per 100 ml, which is about 0.006-0.025% by weight, while the caffeine content in coffee is about 20-70 mg per 100 ml, which is about 0.02. 0.07 weight equivalent.

With a nasal spray, a quantity of about 30μΙ per spray is applied. Since caffeine administration via the nasal mucosa has a much faster effect than oral administration, as it has been able to reach the brain directly, even smaller amounts are required. Therefore, a preferred caffeine concentration may be between 0.1 to 3 wt%. 2% caffeine in the formulation would correspond to an applied amount of 0.6 mg per 30μΙ spray.

Guarana powder may also be included as an activating substance; 3g guarana powder dissolved in water, correspond to a caffeine content of

150mg. A spray of 30 μΙ would accordingly contain 0.045 mg guarana or caffeine.

The addition of at least one wound healing promoting agent prevents irritation and damage to the nasal mucous membrane, e.g. through certain essential oils, before. If damage to the nasal mucous membrane should already be present in the application, reliable wound healing can be ensured despite the use of irritating oils if necessary. In a preferred embodiment, the at least one essential oil is selected from the group consisting of menthol-containing essential oils, camphor-containing essential oils, cajuput oil, grapefruit oil, eucalyptus oil, lime oil, rosemary oil, orange oil, lime-containing essential oils, citron oil, pine oil, Bergamot oil, clove oil, ginger oil, peppermint oil, aniseed oil, mint oil, lemongrass oil, cedarwood oil, niaouli oil, jasmine oil, lineol, eugenoil, a-

Pinene, spearmint oil, blood orange oil, lavender oil, clary sage oil, mountain pine oil, as well as mixtures and / or combinations thereof.

A further preferred embodiment provides that the stimulating substance is selected from the group consisting of xanthines, in particular caffeine (teein), theophylline, theobromine, extracts of cola seeds, exacerbations. from leaves of Erythroxyium species and / or extracts of

Guarana species; taurine; Mono- and / or oligosaccharides, in particular glucose and / or dextrose; Nicotine; Ginko extracts, extracts of green tea, L-carnitine, creatine, lecithin, ginseng extracts, orotic acid and / or salts thereof, in particular magnesium orotate, choline, nicotinamide,

Dimethylaminoethanol (Deanol), omega-3 fatty acids, Icelandic moss extract, capsiacin and / or mixtures and / or combinations thereof.

It is further preferred that, independently of one another, the concentration of the at least one essential oil, based on the total composition, is from 0.01 to 2.5% by weight, preferably from 0.05 to 2% by weight, particularly preferably from 0 , 2 to 1% by weight and / or of the at least one stimulating substance, based on the total composition, of 0.005 to 5% by weight. Furthermore, the concentration of the at least one wound-healing-promoting substance can be from 0.001 to 6% by weight, preferably from 0.1 to 5% by weight, particularly preferably from 0.5 to 3% by weight.

In a particularly preferred embodiment, the composition contains as at least one stimulating substance at least one of the following substances and / or combinations thereof:

a) caffeine in a concentration of 0.01 to 0.05% by weight,

b) taurine in a concentration of 0.05 to 0.5% by weight,

c) ginko extract in a concentration of 0.01 to 15% by weight, and / or d) extracts of green tea in a concentration of 0.01 to 15% by weight,

in each case based on the entire composition.

In addition, it is possible for the composition to comprise at least one adjuvant selected from the group consisting of viscosity boosters, in particular hyaluronic acid, carboxymethylcellulose, hydroxypropylmethylcellulose and / or glycerol; at least one solubilizer, in particular polyvinylpyrrolidone (polyvidone), emulsifiers, in particular macrogol-25-cetostearyl ether (Cremophor A25), macrogolglycerol ricinoleate (Cremophor EL) and / or lecithin; Polysorbates, in particular TWEEN; Osmoregulators, in particular glycerol, sorbitol, sodium or potassium or citrate salts and / or mixtures thereof; Antioxidants, especially coenzyme Q10, Vitamin A, rosemary oil, tocophenol, ascorbyl palmitate, Vitamin E, Vitamin C and / or combinations thereof; and mixtures and / or combinations of the aforementioned substances. Substances that have a calming effect on the mucous membrane, eg

Tocotrienols, algae oil, perilla oil, poppy seed oil, singer oil, evening primrose oil, etc. may also be included in the composition.

In a further preferred embodiment, the composition

Preservative included. In addition, however, it is also preferred that the composition be free of preservatives.

Moreover, it is advantageous if the composition is free of quaternary ammonium compounds, in particular benzalkonium chloride. It has been shown that such compounds can damage the nasal mucosa, so that in their absence an extremely gentle nasal spray is obtained.

Further, it is advantageous if the composition comprises ad 100% by weight of a liquid carrier phase, in particular water, oils, triglycerides and / or fatty acid esters.

The composition is particularly preferably in the form of an emulsion, in particular an irkoemulsion.

Formulation of the essential oils as an emulsion and especially as a microemulsion avoids the problem of o durability

Essential oils are easily degradable by

-> oxidation

-> UV radiation

-> volatile substance (high evaporation rate) o Good tolerability for the nasal mucosa In the case of medical devices and pharmaceutical formulations, a consistent quality of the product must be given over the storage and consumption period after the first opening,

For volatile and oxidation-sensitive substances, the challenge posed by multidose dosing systems is particularly challenging.

Volatile substances, such as essential oils, are sensitive to external factors such as atmospheric oxygen, light and heat, as well as oxidative degradation processes mediated by metal ions, which are found in trace amounts in excipients.

In the prior art, the stability of the essential oils is solved by adding very high initial concentrations of essential oils and / or by

Use of alcoholic co-solvents or by quaternary ammonium compounds such as benzalkonium chloride. Alcohols and quaternary ammonium compounds irritate and damage the nasal mucosa. The present invention enhances the stability and compatibility of the essential oils by formulation in microemulsions.

The microemulsion contains a dispersion of nanoscale oil droplets in the aqueous continuous phase. The ethereal oil droplets are enveloped by adsorbed emulsifier / solvent mediator, which protects the droplets in a protective way and stabilizes them. This forms a protection against degradation by oxidation. In addition, the rate of evaporation of the dispersed oil droplets is reduced relative to the rate of un emulsified oil. Also a lovely effect of the essential oils themselves, when applied to the

Skin and mucous membranes are described. Above all, essential oils containing a high content of phenols and aldehydes can irritate skin, eyes and mucous membranes. The inclusion of the essential oils in emulsifier droplets can also reduce a irritating effect of the essential oils on the mucous membranes.

The nasal application can be achieved by atomizing the composition and / or by dribbling the nasal mucous membranes with the composition. For inhalation, for example, a sputtering or the formation of an aerosol can be made from the composition. It is preferred if the nasal application is carried out 1 to 10, preferably 2 to 4 times per day. However, the number of Applikattonen is preferably situation-dependent and vote on the case of need; ie it can be used mainly in special stress and stress situations and thus not regularly.

For each nasal application procedure, preferably between 5 and 200 μΙ, preferably between 100 and 200 μΙ, particularly preferably between 130 and 150 μΙ of the nasal spray are applied. In particular, the composition is for stimulating and / or stimulating the sympathetic nervous system; before, during and / or after exercise; before, during, and / or after situations requiring increased attention; to increase concentration; to increase mental performance; before, during and / or after driving; for the prophylaxis and / or treatment of jet lag; used for the prophylaxis and / or treatment of fatigue, fatigue and / or fatigue and / or to improve well-being and / or smoking cessation. According to the invention, a method for non-therapeutic stimulation and / or activation of the sympathetic nervous system is also specified, in which the composition described above is administered nasally and / or inhaled. With regard to the composition and the possible applications, reference is made to the preceding embodiments.

According to the invention, a nasal spray and nasal drops are also disclosed which each contain at least one essential oil, at least one stimulating substance and at least one wound healing substance. The nasal spray and the nasal drops are based on the composition described above. With regard to preferred embodiments of this composition, reference is also made to the above-mentioned referenced.

The composition is used according to the invention for invigorating, refreshing, stimulating and increasing the concentration and / or performance of a human or an animal.

By adding the stimulant nicotine, the composition can also be used for smoking cessation.

The present invention will be explained in more detail with reference to the following embodiments, but without limiting the invention to the specific details.

Preferred applications:

• Sports,

• exam learning / exam preparation,

• Situations requiring increased attention,

• increase in concentration,

• Increasing mental and / or physical performance,

• Drive,

Jet lag,

• In case of exhaustion / fatigue / tiredness,

• improvement of well-being.

Possible formulation ingredients: 1) Essential oils

The concentration of the oils is in the range of 0.01 to 5 wt .-%, preferably in the range of 0.05 to 2.5 parts by weight, particularly preferably in the range of 0.1 to 1 wt .-%.

Listed below are some examples of essential oils with effects described in the literature, in particular with stimulating, refreshing, invigorating, activating and / or concentration-promoting effects. > Menthol

Stimulation of the cold-sensitive TRPM8 receptor, which is responsible for the sensation of cold;

- analgesic properties mediated by selective activation of the κ opioid receptor; Fighter

- invigorating, cooling and warming, anti-inflammatory;

- by irritation of cold sensations of conductive nerve endings cooling effect;

> Cajuput oil

- The oil consists mainly (50-60%) of cineole; additionally L-pinene, terpineol and several aldehydes are included;

- antibacterial, anti-inflammatory, expectorant, analgesic, cooling, refreshing, invigorating, increases concentration;

> Eucalyptus oil

- stimulating and refreshing, antifungal, antiviral, antibacterial, cooling, anti-inflammatory; Grapefruit oil

- astringent, cooling, invigorating, improves the circulation and stimulates the lymphatic system, abstergent, antiseptic. Grapefruit oil increases the joie de vivre;

> Omelette oil

- antiseptic, antiviral, refreshing, improves mood and well-being;

> Rosemary oil

- stimulating, improves circulation, antiseptic, tonus balancing and helps with muscle aches;

> Orange Oil, Lemone Oil, Lemon Oil, Pine Oil, Bergamot Oil, Clove Oil, Ginger oil, peppermint oil, aniseed oil, mint oil, etc. 2) Stimulants

Stimulants in a concentration of 0.005 to 5 wt .-%, while caffeine preferably in the range of 0.01 to 0.05 wt .-%, and taurine preferably in the range of 0.05 to 0.5 wt .-%,

Below are some examples of effects described in the literature.

> Caffeine, tein

- stimulation of the central nervous system;

- increase the contraction force of the heart;

- increase in heart rate (increase in heart rate);

- bronchodilation (bronchodilation);

- Effect on blood vessels: Caffeine has a narrowing effect on vessels in the brain, widening to those in the periphery; Due to the cerebral vasoconstrictive effect, there is a reduced blood flow velocity in the brain.

> Taurine

Taurine is a simple sulfur-containing free amino acid; often in electrically excitable tissues such as the brain, retina, heart, skeletal muscles; it is involved in many physiological processes, e.g. Osmoregulation, lipid metabolism; intracellular calcium regulation, neuronal development, neuromodulation and cell protection.

Theophylline, theobromine;

> Glucose / dextrose;

> Nicotine;

> Extracts of colasamen;

Extract of leaves of erythroxylum species or high caffeine guarana species;

> NADH / NADPH. 3) Herbal extracts that promote mental performance / concentration

> Ginko extracts {0.01-15% by weight)

> Green tea extract (0.01-15% by weight)

> decaffeinated coca leaf extracts

> Kombucha extract

4) auxiliaries

> Viscosity enhancers (e.g., hyaluronic acid, hydroxypropylmethylcellulose, glycerin);

Solvents (e.g., Polyvidone, Tween, SPAN, PEG castor oil, PEG-hydrogenated castor oil, polyoxyethylene stearate, etc.);

> Osmoregulator;

Antioxidants (e.g., Q10, Vitamin E, Vitamin C, Vitamin A, taurine, etc.);

> with or without preservatives.

example 1

Example 2

Ingredients Quantity (% by weight)

Menthol 0.02

Eucalyptus 0.02

Camphor 0.01

Polysorbate 80 0.05

Glycerol 1.43

Hyaluronic acid 0.2

Caffeine 0.1-3

Taurine 0,1-3

Sodium citrate 0.85

Citric acid 0.005

Water ad 100 Example 3

Example 4

Invigorating triglyceride-based spray

Ingredients Quantity (% by weight)

Niaouli 0.05

Lemongrass 0.1

Caffeine 0.1-3

Castor oil 5

Dexpanthenol 0.05-2.5

Water 10

Lecithin 1-5

Miglyol ad 100

Example 5

Invigorating Ayuveda-based spray

Example 6

Energizing spray based on fatty acid ester or organogel

Ingredients Quantity (Wt.)

Niaouli 0.3

Orange oil 0.5

Lecithin (Epikuron 200) 3-7.5

Ascorbyl palmitate 0.05

Q10 0.02

Caffeine 0.1-3

Water 0.6-10

Chondroic acid 0.01-0.6

Isopropyl myristic ad 100 Example 7

Energizing spray based on fatty acid esters

Example 8

Invigorating spray on a watery basis

Ingredients Quantity (% by weight)

Menthol 0.5

Caffeine 0.1-3

Taurine 0,1-3

Chondroic acid 0.05-0.2

Sodium carboxymethylcellulose 0.5

Q10 0.03

Glycerol 0.09

Polysorbate 60 0.5

Sodium citrate 0.75

Citric acid 0.02

Water ad 100 Example 9

Invigorating spray on a watery basis

Example 10

Invigorating spray on a watery basis

Ingredients Quantity (% by weight)

Menthol 0.3

Cajuput oil 0.05

Caffeine 0.1-3

Decosahexaenoic acid / eicosapentaene-0.2 acid mixture

Macrogolglycerol ricinoleate 0.3-0.6 (Cremophor EL)

Hyaluronic acid 0.1

Xylitol 3.2

Citric acid 0.05

Sodium citrate 0.85

Water ad 100 Example 11

Invigorating system based on water

Example 12

Invigorating seawater based spray (hypertonic)

Ingredients Quantity (% by weight)

Whistle rmmzöi 0,5

Lemon oil 0.3

Caffeine 0.1-3

Dexpanthenol 0.2

Macrogolgiycerol ricinoleate {Cremophor 0.3-0.6 EL)

Carboxymethylcellulose 1.5

Sodium chloride 1.5 to 3

Citric acid 0.005

Sodium citrate 0.85

Water ad 100 Example 13

Invigorating seawater-based spray (isotonic)

Example 14

Invigorating nasal spray (smoking cessation)

Ingredients Quantity (% by weight)

Lime oil 0.08

Macrogolglycerol ricinoleate (Cremophor 0.3-0.6 EL)

Hyaluronic acid 0.05-0.2

Nicotine 0.05-0.2

Sodium citrate 0.85

Citric acid 0.005

Sodium chloride 0.48

Water ad 100 Example 15

Invigorating system based on water

Example 16

Invigorating system based on water

Ingredients Quantity (% by weight)

Niaouli 0.05

Oleum Aurantii 0.1

Cremophor EL 0.5

Guarana powder 3-6

Xylitol 3.2

Sodium citrate 0.85

Citric acid 0.005

Hyaluronic acid 0.05

Water ad 100

Claims

claims

1. Use of a composition containing

a} at least one essential oil,

b) at least one stimulating substance, as well

c) at least one wound-healing-promoting substance selected from the group consisting of hyaluronic acid, dexpanthenol and chondroitin acid,

for nasal and / or inhalation application.

2. Use according to the preceding claim, characterized in that the at least one essential oil is selected from the group consisting of menthol-containing essential oils, kampferhal- term essential oils, cajuput oil, grapefruit oil, eucalyptus oil, lime oil, rosemary oil, orange oil, lime-containing essential oils, lemon oil, pine oil, bergamot oil, clove oil, ginger oil, peppermint oil, aniseed oil, mint oil, lemongrass oil, cedarwood oil, niaouli oil, jasmine oil, lineol, eugenoil, a-pinene, spearmint oil, blood orange oil, lavender oil, muscatel oil, mountain pine oil and mixtures and / or combinations thereof.

3. Use according to one of the preceding claims, characterized in that the at least one stimulating substance is selected from the group consisting of xanthines, especially caffeine (teein), theophylline, theobromine, extracts of colas, extracts of leaves of erythroxy species and / or extracts of guarana species; taurine; Mono- and / or oligosaccharides, in particular glucose and / or dextrose; Nicotine; Ginko extracts, extracts of green tea, L-carnitine, creatine, lecithin, ginseng extracts, orotic acid and / or salts thereof, in particular

Magnesium orotate, choline, nicotinamide, dimethylaminoethanol (Deanol), omega-3 fatty acids, Icelandic moss extract capsiacin and / or mixtures and / or combinations thereof.

4. Use according to one of the preceding claims, characterized in that independently of one another the concentration a) of the at least one essential oil, based on the total composition, of 0.05 to 2.5 wt .-%, preferably from 0.05 to 2 wt .-%, particularly preferably from 0.1 to 1 wt .-% b) of the at least one stimulating substance, based on the total composition, from 0.005 to 6 wt .-%, preferably from 0.1 to 5 wt. -%, more preferably from 0.5 to 2.5 parts by weight and / or

c) the at least one wound healing substance from 0.001 to 6 wt .-%, preferably from 0.1 to 5 wt .-%, particularly preferably from 0.5 to 3 wt .-% is.

5. Use according to one of the preceding claims, characterized in that it contains as at least one stimulatory substance at least one of the following substances and / or combinations thereof:

a) caffeine in a concentration of 0.01 to 0.05% by weight b) taurine in a concentration of 0.05 to 0.5% by weight,

c) Ginko extract in a concentration of 0.01 to 15% by weight

and or

d) extracts of green tea in a concentration of 0.01 to 15% by weight,

in each case based on the entire composition.

6. Use according to one of the preceding claims, characterized in that the composition comprises at least one adjuvant selected from the group consisting of viscosity enhancers, in particular hyaluronic acid, hydroxypropylmethylcellulose and / or glycerol; at least one solubilizer, in particular polyvinylpyrrolidone (polyvidone), emulsifiers, in particular macrogol-25-ceto stearyl ether (Cremophor A25), macrogolglycerol ricinoleate (Cremophor EL) and / or lecithin; Polysorbates, in particular TWEEN; Osmo- regulators, in particular sodium or potassium salts; Glycerol, antioxidants, especially coenzyme Q10, vitamin E, vitamin C and / or combinations thereof; and mixtures and / or combinations of the aforementioned substances.

Use according to any one of the preceding claims, characterized in that the composition contains preservatives or is free of preservatives.

Use according to one of the preceding claims, characterized in that the composition is free of quaternary ammonium compounds, in particular benzalkonium chloride.

Use according to one of the preceding claims, characterized in that the composition ad 100 wt .-% comprises a liquid carrier phase, in particular water, oils and / or triglycerides.

Use according to one of the preceding claims, characterized in that the composition is in the form of an emulsion, in particular a microemulsion.

Use according to one of the preceding claims, characterized in that the nasal application is carried out by atomizing the composition and / or by dribbling the nasal mucous membranes.

Use according to one of the preceding claims, characterized in that the nasal administration is carried out, if necessary, 1 to 10, preferably 2 to 4 times per day.

Use according to one of the preceding claims, characterized in that between 5 and 100 μΙ, preferably between 10 and 60 μΙ, particularly preferably between 20 and 30 μΙ of the nasal spray are administered per nasal application process.

14. Use according to one of the preceding claims for stimulation and / or activation of the sympathetic nervous system; before, during and / or after exercise; before, during, and / or after situations requiring increased attention; to increase concentration; to increase mental performance; before, during and / or after driving; for the prophylaxis and / or treatment of jet lag; for the prophylaxis and / or treatment of tension, fatigue and / or tiredness and / or for the improvement of well-being and / or smoking cessation.

15. A method for non-therapeutic stimulation and / or stimulation of the sympathetic nervous system, wherein a composition containing

a) at least one essential oil,

b) at least one stimulating substance, as well

nasally applied and / or inhaled.

16. Nasal spray containing

a) at least one essential oil, as well

b) at least one stimulating substance, as well

17. Nasal drops containing

a) at least one essential oil,

b} at least one stimulating substance, as well

c) at least one wound-healing-promoting substance selected from the group consisting of hyaluronic acid, dexpanthenol and chondroitinic acid.