DE202013005637U1 - Agent with tocotrienol for burns from the sun, radioactive rays or heat - Google Patents

Abstract

Skin-applying agent consisting of a lipophilic substance containing from 0.1% to 70% by weight of tocotrienols, derivatives of tocotrienols, tocotrienol-rich fractions of natural products or mixtures thereof, for the purpose of treating or ameliorating the effects of radioactive radiation, UV -Stahlung, sunlight, X-rays, medical radiation or thermal burns and their consequences, or to prevent these effects.

Description

short version

Technical problem of the invention = technical task and objective

• The treatment of burns due to radioactivity, ultraviolet light, heat or medical radiation and the prevention of known exposures.
• Reduction of damage at the cellular level, alleviation of pain, acceleration of healing, protection against knock-on effects due to mutations.
• Relief or treatment of inflammatory processes.
• Avoidance of side effects and toxic effects in the mentioned tasks.

Solution of the problem or the technical task

By tocotrienols a substance is available for which the corresponding effect has been proven by scientific studies.

Tocotrienols have the added benefit of the anti-cancer effect (protection and treatment), which is of particular importance in radiation exposure.

By topical application, a much higher concentration in the desired range can be achieved than by systemic administration (for example orally or by injection).

By selecting a low-viscosity oil (for example MCT) atomization of the agent can be facilitated, whereby the application is much easier. Low-viscosity oils also remain much shorter on the skin, which is beneficial both medically and for practical use.

field of use

• 1. „After Sun” zur besseren Verträglichkeit von Sonnenbädern
• 2. „After Sun” zur Linderung und Behandlung von Sonnenbrand
• 3. „Pre Sun” zur Vorbehandlung der Haut vor Sonnenbädern, vor Auftragen des Sonnenschutzes.
• 4. Mittel zur Schmerzlinderung und Heilungsverbesserung bei Verbrennungen
• 5. Hautschutzmittel für die Anwendung vor medizinischen Bestrahlungen
• 6. Hautberuhigungsmittel bei entzündlichen Hautkrankheiten wie Neurodermitis

The present invention has the following main fields of application:

• 1. "After Sun" for better compatibility of sunbathing
• 2. "After Sun" for the relief and treatment of sunburn
• 3. "Pre Sun" for the pre-treatment of the skin before sunbathing, before applying the sunscreen.
• 4. means for pain relief and healing improvement in burns
• 5. Skin protection product for use before medical irradiation
• 6. Skin sedative for inflammatory skin diseases such as atopic dermatitis

Patent

• – Behandlung von Sonnenbränden und anderen Strahlungsverletzungen
• – Anreicherung der Haut mit schützendem Vitamin E vor der Strahlungsexposition
• – Behandlung bzw. Linderung von Verletzungen durch Hitze (Verbrennung)
• – berührungsfreies/armes topisches Auftragen von T3 in den genannten Fällen
• – berührungsfreies Aufbringen von T3 als Aerosol bei Entzündungsvorgängen wie Neurodermitis

The present invention relates to an agent with tocotrienols which is suitable for

• - Treatment of sunburns and other radiation injuries
• - Enrichment of the skin with protective vitamin E before radiation exposure
• - Treatment or relief of injuries due to heat (burning)
• - Non-contact / poor topical application of T3 in the cases mentioned
• - Non-contact application of T3 as an aerosol during inflammatory processes such as atopic dermatitis

Designation of Inventor:

• Inventor is Ingo Schmidt-Philipp, diploma computer scientist (FH), lenses 3a, 87448 Waltenhofen

Idea of the invention

Tocotrienols are isomers of the vitamin E family that differ from tocopherols by a triunsaturated side chain. As a result, they penetrate skin, tissue and cells much faster and better than tocopherols. Scientific studies have shown that tocotrienols can effectively prevent and / or repair cell damage from radioactive and UV radiation. The excellent effect of tocotrienols in heat and sun burns has been confirmed in empirical tests. In addition to tocotrienols a strong anti-cancer effect and an anti-inflammatory effect has been demonstrated.

Medium chain fatty acids, such as caprylic acid (C8: 0), are found in some natural triglycerides (for example, coconut oil) and in neutral oil (MCT oil). They have a marked inhibiting effect on bacteria and fungi. MCT oil is characterized by high levels of fluidity and is absorbed quickly into the skin without leaving a greasy feeling.

Both elements are oil soluble (lipophilic). Oils are necessary for the solution and dilution of tocotrienol extracts and at the same time improve penetration of the active ingredients into the skin as a penetration enhancer (or permeation enhancer).

Combining these two elements in an oil (or emulsion) yields a product which has the following advantages:

Advantages of the invention

• 1. The excellent effect of Tocotrienole in radiation injuries can be experienced in a short time by a significant pain relief.
• 2. By topical administration, significantly higher concentrations can be achieved than with systemic administration (eg, oral or injected).
• 3. Radiation injuries are associated with increased cancer risk. On the one hand, the tocotrienols counteract this by neutralizing mutagenic ROS and NOS, and on the other hand by the marked anti-cancer effect even with existing mutations due to apoptosis.
• 4. Tocotrienols are very good anti-inflammatory, the mixture with a thin oil, a fast-absorbing and aufzutragendes anti-inflammatory agent is achieved.
• 5. Medium-chain fatty acids have a markedly antibacterial (and fungicidal) effect. This helps to prevent infections.
• 6. Tocotrienols are non-toxic and side-effect free.
• 7. Using a low-viscosity oil results in a mixture that can also be sprayed. This allows a contactless application of the lipophilic components, which is of great advantage in pain-sensitive or pressure-sensitive skin.

State of the art

A number of studies have identified the effects of tocotrienols on both radioactivity and UV radiation.

For example, mice were exposed to a high dose of radiation that survived only 15% within 30 days. By administration of tocotrienols prior to radiation exposure, all (100%) of the experimental animals survived. The systemically given amounts were, however, very high.
(This study: Mechanism of radioprotection by δ-tocotrienol: pharmacokinetics, pharmacodynamics and modulation of signaling pathways, PMID: 22674714 )
(Example study for UV light: Dietary tocotrienol reduces UVB-induced skin damage and sesamin enhances tocotrienol effects in hairless mice., PMID: 18490840 )

To date, tocotrienols are only seen on the market in oral form or in relatively low concentrations in topical products.

The utility model 20 2013 003 675.3 describes the use of medium-chain fatty acids with tocotrienols, but only for the care of the oral cavity.

tocotrienols

Tocotrienols are naturally occurring isomers of vitamin E. They are characterized by many properties that are not found in tocopherols.

Tocotrienol-rich vitamin extracts have been produced from certain vegetable oils for several decades. Such extracts are also called TRF (tocotrienol rich fraction). They are manufactured and marketed on a large scale for nutritional supplements and food, and are thus available at relatively low prices.

Tocotrienols are characterized by the fact that they penetrate and spread much better into the skin and other tissues than conventional vitamin E. In vivo, tocotrienols are characterized by a 40- to 60-fold higher antioxidant activity on the cell membranes.

Tocotrienols have a half-life of 3-5 hours, a shorter residence time than tocopherols. Studies and practical experience confirm the anti-inflammatory effects of tocotrienol-rich oils.

Tocotrienols occur in nature predominantly as alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol and delta-tocotrienol. The strongest anti-inflammatory effect is currently evidenced for gamma-tocotrienol and delta-tocotrienol. These are also referred to as DMT3 (desmethyl tocotrienols).

• – Varianten (Isomere) der verbreiteten Tocopherole (Vitamin E), die sich dadurch auszeichnen, dass sie anstelle des gesättigten Radikals der Tocopherole andere Radikale mit ungesättigten Doppelbindungen aufweisen
• – die natürlichen in der Ölpalme Elaeis Guineensis vorkommenden Tocotrienole, insbesondere mit dreifach ungesättigter Seitenkette
• – die in der Annatto-Pflanze natürlich vorkommenden Tocotrienole
• – die in Getreiden natürlich vorkommenden Vitamin E ähnlichen Substanzen
• – Fraktionen natürlich vorkommender Tocotrienol-Gemische, insbesondere solche, die reich an delta- und gamma-Tocotrienol sind
• – Tocomonoenole, MDT
• – chemisch, synthetisch oder biotechnologisch erzeugte ähnliche Varianten

With tocotrienols for the purposes of this invention are referred to

• - variants (isomers) of the widespread tocopherols (vitamin E), which are characterized in that they have other radicals with unsaturated double bonds instead of the saturated radical of tocopherols
• - The natural occurring in the oil palm Elaeis Guineensis tocotrienols, especially with triunsaturated side chain
• - the tocotrienols naturally occurring in the annatto plant
• - The naturally occurring in cereal vitamin E similar substances
• - Fractions of naturally occurring tocotrienol mixtures, in particular those which are rich in delta and gamma tocotrienol
• - tocomonoenols, MDT
• - chemically, synthetically or biotechnologically produced similar variants

The oil base

By mixing with an oil of vegetable, mineral or synthetic origin, the penetration of tocotrienols into the skin is favored. The use of an oil as a vehicle for the tocotrienols thus serves both the dilution, as well as the effect optimization.

Low-viscosity oils are produced by medium-chain or short-chain fatty acids, such as those found in coconut oil or butter in nature. By transesterification into new triglycerides, for example, various types of MCT oil are produced in the industry from it. Depending on the composition of the fatty acids, particularly low-viscosity oils are formed, as is the case with MCT / 98 with 98% of carpylic acid (c8: 0).

The low viscosity (low viscosity) has the advantage that such oils penetrate very quickly into the skin and leave no greasy feeling on the skin. There is no air / oxygen barrier and lingering layer, which in many cases would be unfavorable in healing and in practical use.

By lipolysis, which takes place spontaneously, on contact with certain substances, by bacteria and by enzymes, free fatty acids are split off. Medium-chain fatty acids inhibit many microorganisms. In this way, the low-viscosity oil base helps to ward off infections that can occur secondarily, for example, in different types of burns.

Other ingredients

As further ingredients in the agent described here are, for example, the following substances.

Sesamin / Sesamolin

These sesame seeds improve the effect of tocotrienols against UV damage.

Gamma-linolenic acid (GLA)

This fatty acid, which is found, for example, in evening primrose oil, has a soothing and anti-inflammatory effect.

Other skin vitamins

Of course, the addition of other skin-friendly agents is useful, such as dexpanthenol.

Dosage of tocotrienols

In the case of a strong radioactive radiation exposure, the maximum achievable concentration must be sought in accordance with the studies. Tocotrienols, as a natural form of vitamin E in the body, are highly regulated.

As a result, an overdose on the skin must not be feared. The penetration of tocotrienols into the skin is promoted by an accompanying oil (penetration enhancer).

Therefore, the agent described should be made from a mixture of tocotrienols with an accompanying oil. If one strives, as described, to apply the (oil mixture by spraying (as an aerosol) on the skin, also a relatively low-viscosity oil must be selected.

The tocotrienols themselves (vitamin E) are relatively viscous.

The concentration of tocotrienols in the finished composition can thus be varied depending on the application and the application strategy. Effective concentrations for the finished agent range from 95% (nearly pure tocotrienol) to 0.1% (for a very low viscosity, low irradiation oil). For application by spraying, mixtures with 1% to 10% tocotrienol are suitable.

The increase of the locally applied dose is easily possible by repeating the application at intervals of about 15 minutes.

In the case of radiation injuries from the sun (sunburn), when touch sensitivity exists, it is advisable to use an oil with low viscosity, which can also be sprayed.

Concentrations of up to 1% (weight percent T3 on average) are referred to as low, up to 5% normal. Upwards, the concentration is limited only by the viscosity and the decrease in skin penetration when the T3 content in the carrier oil falls too low.

Basically, a plentiful dosage should be sought, as an overdose of vitamin E is hardly possible.

For radiation protection, such as anti-inflammatory applications, the use of delta-tocotrienol and gamma-tocotrienol is particularly recommended, as this has been the most effective in studies.

Oral ingestion of tocotrienols against radiation injuries

Oral administration of tocotrienols also provides protection against radiation injuries. Thus, people who took tocotrienols as dietary supplements have reported a much better tolerability of solar radiation.

The oral intake can produce a maximum concentration of only about 3 to 5 micro-moles in the tissue according to the current state of knowledge. This is due to mechanisms in the uptake and excretion of tocochromanols in the body, as well as by the dilution, as the oral agent must be distributed throughout the body.

For the preparation of an oral radiation protection agent from tocotrienols, I propose the use of highly concentrated tocotrienols. EFSA describes 520 mg aTE (alpha tocotrienol equivalents) per day as NOAEL (dose in which no unfavorable effects were observed) and 300 mg aTE as the maximum recommended dose in lifelong daily intake. However, Tocotrienols are hardly included in the calculation of the aTE. For example, the DGE reports 3.3 mg alpha tocotrienol as 1 mg equivalent. Other isomers, in particular the most effective components gamma-tocotrienol and delta-tocotrienol still obtain significantly lower conversion factors of 13.2 or 20, or 100, but which are only specified by the UN or WHO).

If the maximum EFSA recommendation of 300 mg equivalents based on this information is converted to TRF mixtures, they will only be achieved with 1800 to 4000 mg TRF (50%) from palm oil.

As a result, the administration of 2 to 4 grams of TRF per day seems to be appropriate in the case of a strong radiation exposure. Since tocotrienols have a relatively short residence time in the body (half-life about 5 hours after reaching the maximum concentration), the distribution to 2-4 single doses is useful.

Sunscreen and the described invention

The described invention can not replace the avoidance of radiation exposure but merely reduce the effects of the radiation. In the case of solar radiation, therefore, the blocking of the radiation exposure (for example by UV filters) must be aimed first and foremost.

The best radiation protection effect arises when the tocotrienols are already present in the cells before the radiation exposure.

It is therefore close to apply the radiation protection described before sun baths as a "pre-Sun" agent. Then the sunscreen filter can be applied.

It is also advisable to equip the sunscreen with tocotrienol vitamin E.

Application with low radiation exposure

Even with radiation exposure that can be called normal, for example, the sunlight that is necessary for the production of vitamin D in the skin or by the natural radioactivity or cosmic radiation creates a burden on the cell components. Even with "normal" radiation exposure, the described invention serves to avoid radiation damage and the associated faster aging or the occurrence of mutations.

Application of the topical agent as an aerosol

In many cases it is advantageous if the topical agent can be applied without touching the affected skin. This can be achieved by spraying as an aerosol.

In this case, it is advisable to choose as a carrier oil as thin as possible oil base, such as MCT oil.

Application under thermal stress (combustion by heat)

The invention described is excellently suitable for thermal burns. Practical experience has shown that Tocotrienols on the skin, on the one hand, can provide rapid relief of pain and, on the other hand, a rapid healing of the burn is achieved.

Used biological materials of plant origin and their countries of origin

For the purposes of this patent application Tocotrienole of natural origin can be used. So-called TRF extracts from red palm oil from Malaysia and tocotrienol oils from the USA are widespread. Tocotrienols are also produced in Europe from cereals (barley, Hordeum vulgare) and in other countries from rice.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited non-patent literature

• Mechanism of radioprotection by δ-tocotrienol: pharmacokinetics, pharmacodynamics and modulation of signaling pathways, PMID: 22674714 [0012]
• Dietary tocotrienol reduces UVB-induced skin damage and sesamin enhances tocotrienol effects in hairless mice., PMID: 18490840 [0012]

Claims (8)

Skin-applying agent consisting of a lipophilic substance containing from 0.1% to 70% by weight of tocotrienols, derivatives of tocotrienols, tocotrienol-rich fractions of natural products or mixtures thereof, for the purpose of treating or ameliorating the effects of radioactive radiation, UV -Stahlung, sunlight, X-rays, medical radiation or thermal burns and their consequences, or to prevent these effects. The composition of claim 1, wherein tocotrienols are a composition selected from the group consisting of alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, delta-tocotrienol, desmethyltocotrienol, didesmethyltocotrienol, or mixtures thereof; or tocotrienol-rich fractions of natural products, in particular of the palm species Elaeis guineensis, Annato seeds or cereals; or from other synthetically or biotechnologically produced variants of vitamin E. A composition according to any one of the preceding claims using an aerosol-generating mechanism, a propellant or hand-operated spray can, or a pump for the purpose of application to the skin of humans or animals. A composition according to any one of the preceding claims using MCT oil containing 30 to 100% caprylic acid (C8: 0) with 0.5% to 10% of a tocotrienol-rich natural product extract. Agent according to one of the preceding claims for the treatment of cancer, eczema, neurodermatitis or inflammatory phenomena. Agent according to one of the preceding claims with additional incorporation of further skin-active substances according to the prior art, in particular sesamin, sesamolin or dexpanthenol. Oral agent with tocotrienols at a concentration of 0.1% to 70% (by weight) for the purpose of avoiding cell damage by radioactive radiation, UV radiation, sunlight, X-rays and medical radiation. Sunscreen, based on chemical or mechanical filters for protection against UV light, designed as an agent according to claim 1 to 6, for the purpose of improving the sunscreen by transferring Tocotrienols into the skin before the start of radiation exposure.