WO2006089317A1

WO2006089317A1 - Pharmaceutical dosage form effective at microcirculatory level containing at least one flavonoid

Info

Publication number: WO2006089317A1
Application number: PCT/AT2006/000015
Authority: WO
Inventors: Hermine Engl
Original assignee: Hermine Engl
Priority date: 2005-01-14
Filing date: 2006-01-13
Publication date: 2006-08-31
Also published as: EP1888028A1; AT501682A1

Abstract

The invention relates to a mixture of active ingredients, in particular active ingredient mixtures for the field of preventative medicine, containing at least one active ingredient in powder and/or granular form and/or as a mother tincture and/or as a pure substance and/or as an extract. The agent is selected from the group of phytopharmacological agents effective at the capillary and microcirculatory level, preferably a flavonoid and/or a modified flavonoid. Aescin, rutosid, troxerutin, diosmin, hesperidin, gingko, Vitis viniferae (red vine leaves) and/or Ruscus aculeatus (butchers broom) are contained as active ingredient and said mixture optionally contains a vitamin, flavouring, trace element, mineral and/or a further adjunct.

Description

PHARMACEUTICAL MICROCIRCULARLY ACTIVE PHARMACEUTICAL FORM AT LEAST ONE FLAVONOID CONTAINING

The invention relates to an active ingredient mixture, in particular active ingredient mixture for the preventive health sector, comprising at least one active ingredient, which is present in powdery and / or granulated form and / or as mother tincture and / or as pure substance and / or as extract, from the group of capillary-active, microcirculatory effective phytopharmacological agents, preferably a flavonoid and / or a modified flavonoid. Likewise, the invention relates to a method for producing a drug mixture.

If there is a slowdown in the blood flow, inflammatory mediators will be released. Longer existence of these inflammatory mediators with only short recovery phases initiate processes requiring treatment.

Phytopharmaceuticals are well-researched herbal ingredients, which are used successfully in conventional medicine. Therapeutic efficacy has been demonstrated in scientific clinical trials and medical experience.

A special group of phytopharmaceuticals are flavonoids. Therapeutic compositions are known, for example, from EP 0 417 209 B1.

The object of the invention is to provide a drug mixture which avoids the one hand, the above health disadvantages and on the other hand as a preventive means, for example as a drink or as a functional drink or as a dragee, before long or long trips, such as long-haul flights, but also train -, bus or car travel or sedentary activity can be taken to prevent impairment of physical well-being or possible health venous damage. The object is achieved by the invention.

The active ingredient according to the invention is characterized in that in one

Maximum daily dose of a finished product of at least one of the following active substances

Aescin at a dose of 0.1 to 150 mg, preferably 1, 5 to 25 mg, especially 5 to 20mg.

Rutoside at a dose of 0.1 to 800 mg, preferably 1, 5 to 75 mg, especially 5 to 25 mg, troxerutin at a dose of 0.1 to 300 mg, preferably 5 to 75 mg. in particular 5 to 30 mg,

Diosmin with a dose of 0.1 to 600 mg, preferably 1, 5 to 300 mg, in particular 5 to 30 mg,

Hesperidin at a dose of 0.1 to 100 mg, preferably 1.5 to 50 mg, in particular 5 to 30 mg,

Gingko at a dose of from 0.1 to 120 mg, preferably from 1.5 to 100 mg, in particular from 5 to 30 mg,

Vitis viniferae (red vine leaves) at a dose of 0.1 to 720 mg, preferably

35 to 500mg, especially 5 to 150 mg, and / or Ruscus aculeatus (butcher's broom) at a dose of 0, 1 to 450 mg, preferably

1, 5 to 100, in particular 5 to 50 mg is contained.

With the invention, it is for the first time possible to counteract the formation of free radicals and inflammatory mediators by administration of the active substance, preferably in liquid administration. The prevention or prophylaxis serves to ensure that there are no above-mentioned problems, especially with long-term travel.

Little exercise, intense mental work and recurring stress situations have a negative effect on the oxygen supply and total body blood flow. In particular, the nutritive nutrition-Kapiliarkreislauf suffers. Especially with long flight, train and bus travel and sitting office work, the return flow of blood from the legs to the heart is impaired. The airlines, for example, fear complaints about the occurrence of so-called travel thrombosis.

In order to prevent possible complaints of long-term travelers in terms of health protection, the active compound mixture according to the invention as a functional beverage provides optimum protection against possibly occurring congestive consequences of the blood flow. First, noticeable effects of an incipient functional impairment on the general well-being are fatigue, fatigue, dizziness in the head; Loss of intellectual capacity and also an uncomfortable feeling of heaviness in the legs.

Travel thrombosis can be prevented in addition to conscious fluid intake by appropriate regular physical exercise.

Sufficient fluid intake serves to favor the physiological blood flow. If the active ingredient according to the invention is administered, this provides relief for the congestion problem during long journeys.

For a qualitative increase in the effectiveness of trace elements or minerals - as later described - added.

A preventive measure against complaints outlined above takes place by the, preferably continuous, oral intake, for example drinking the drink solution according to the invention, shortly before the trip and especially during the journey or during the sitting activity.

According to the invention is as an active ingredient from the group of phytopharmaceuticals, preferably aescin and / or water-soluble or micronized flavonoids, such as rutin and / or rutoside and / or diosmin and / or hamamelis and / or ginkgo and / or hesperidin and / or red vine leaves and / or Ruscus aculeatus (butcher's broom).

These vascular active agents from the plant area protect vascular structures from harmful influences, as they

* Prevent reactions that first develop in the microcirculation area during slowed blood flow and damage cell structures in the vessel and in the immediate vicinity

• The flow properties of the blood improve »the flow velocity, especially in the area of the smallest

Increase vessels

In addition, individual active ingredients have even more advantages:

Aescin, for example, simultaneously tones the vessels. Furthermore, Aescin lowers or regulates pathologically increased vascular permeability and counteracts the formation of edema.

Rutin or rutoside is readily soluble in water. It reduces capillary permeability, thereby reducing the permeation of macromolecules and thus reducing the accumulation of water in the connective tissue.

On the one hand, diosmin and hesperidin lead to a strengthening of venous capacity and toning and, on the other hand, reduce pathologically increased capillary permeability and an increase in capillary resistance.

Gingocofiavonglycosides, obtained from gingko biloba leaves, have a multifactorial effect on the impaired functional unit of blood-vessel tissue. It improves microcirculation and fluidity of the blood as a result of lowering the blood flow

Blood viscosity. Also beneficial is an increase in RBC flexibility, a reduction in the tendency for RBC aggregation, inhibition of platelet aggregation, and an increase in blood flow velocity. In addition, the burden-induced leucocyte accumulation and vascular adherence is reduced. The increased capillary permeability is reduced.

The active ingredient quercetin or isoquercitrin, contained in the extract of the red vine leaves, provides protection of the vascular epithelium by stabilizing the membranes and increasing elasticity. There is a normalization of vascular permeability. As a result, there is a reduced extravasation of plasma, proteins or water into the vessel surrounding interstitial tissue, as with all these vasoactive phytopharmaceuticals.

The Ruscus aculeatus (mouse dome) has the above-mentioned positive properties.

According to a particular feature of the invention, at least one vitamin, such as, for example, ascorbic acid, is present at a dose of 30 to 1,000 mg, preferably 60 to 200 mg. Alternatively, the active ingredient is admixed with a preferably water-soluble vitamin, for example ascorbic acid. The addition of vitamin C allows the antioxidant mechanism to catalyze metabolism.

According to a further particular embodiment of the invention, at least citric acid and / or salts thereof are contained at a dose of 1 to 10 g, preferably 4 to 6 g. As taste plays a dominant role in market positioning, this addition is certainly beneficial.

According to a further feature of the invention, at least one flavoring agent is contained at a dose of 0.1 to 20 g / l. It can not be denied that a consumer's liking better positions the drink solution on the market.

According to a particular embodiment of the invention, at least one flavoring, in particular a natural flavoring, such as lemon, lime, blackcurrant, blueberry, cherry, orange, Mandarin, Grapefruit, Almond, Pineapple, Blue Grape, White Grape Juice. Elderberry, strawberry, sea-buckthorn flavor or citrus flavoring with a dose of 50 to 1,000mg, preferably 200 to 700mg. The addition of aromatics has shown to be very tasty in terms of taste. According to a further advantageous embodiment of the invention, at least one additive, preferably a silicate or a silicon dioxide and / or a binder, such as cellulose fibers included. An improvement in the consistency is to be expected from these additives.

According to a further embodiment, at least one trace element or mineral substance, such as magnesium, calcium, potassium or sodium, with a dose of 10 to 2,000 mg, preferably 200 to 500 mg, contained. By adding these minerals, the substance mixture is enhanced in its qualitative effectiveness.

According to a further feature of the invention, at least one amino acid is contained at a dose of 0.01 to 200 mg, preferably 1 to 20 mg. Amino acids play an important role in nutritional science, so that their addition is certainly beneficial.

According to a further embodiment of the invention, at least one food colorant, in particular a natural food colorant, such as, for example, quinoline yellow, beta carotene or yellow-orange "S", is of course an appealing visual impression of the drink solution for a certain market conquest of invaluable advantage.

According to a particular embodiment of the invention, at least one sweetener, such as saccharin sodium, sodium cyclamate, glucose, glucose, aspartame, dextrose, maltodextrin, sorbitol, xylitol, acesulfame, cane sugar, inulin or fructose, is included. As already mentioned, is next to the optical

Impression, the taste of extraordinary importance for a market success. According to a very important and particular feature of the invention, at least one active ingredient according to claim 1 is included at a dose that meets the requirements of a dietary supplement. Due to the indicated dosage of the individual active ingredients, this beverage can be positioned on the consumer goods market as a dietary supplement.

Especially in today's standard containers with a capacity of 0.25 to 0.33 liters, it is an ideal companion when traveling. Above all, it is also in today's trend, as it can be produced alcohol-free and will maintain its focus in the health sector.

The requirements of a food supplement are in the sense of veno-donating, blood flow supporting, the prevention of venous congestion serving, edema-protective, edema-reducing and / or vascular sealing and / or endothelium stabilizing and / or anti-inflammatory and / or antioxidant (antiaging) properties to see so that due especially at Long-haul flights and similar loads, such as long trips of all kinds, with appropriate sedentary activity, special physical stress (military, surgery), in competitive sports and / or mental stress support in terms of venous blood flow improvement is offered.

According to one embodiment of the invention, the finished product is as extract mixture and / or as a functional beverage and / or dragee (s) and / or as a tablet (s) and / or as granules and / or as effervescent powder and / or syrup and / or as a drinking concentrate and / or as Aufschwemmlösung and / or as chewing gum and / or as a two-phase pack before. The active ingredient mixture according to the invention, in whatever composition, does not limit any of the possible administration forms. Each dosage form has its positive sides. For example, dragees are more space-saving than bottled drinking solutions. On the other hand, however, drinking solutions contribute again to the balance of the fluid balance. So it can be chosen the most appropriate form. According to an advantageous embodiment of the invention, an alcoholic or alcohol-free solvent, for example water, fruit juice, tea, mineral water o. The like. Used for the finished product as a solvent. In particular, it could be offered as a non-alcoholic wellness drink and / or functional nutritional supplement. This drink is therefore ideal as a preventative travel drink for long-term travelers, as for long-haul flights or long train rides. It prevents vascular changes in the microcirculation area and thus those venous congestions that are as well as a factor in the development of travel thrombosis.

According to a further feature of the invention is at least one homeopathic agent, for example Lachesis and / or arnica and / or escin and / or rutin and / or rutoside and / or diosmin and / or hamamelis and / or gingko and / or hesperidin and or red vine leaves , contain. The use of these homeopathic remedies helps to increase the body's defense.

According to a particular embodiment of the invention, at least one of the active substances aescin and / or rutoside and / or diosmin and / or gingko and / or hesperidin and / or red vine leaves is admixed in homeopathic form in aqueous solution in the dose C20 to C40, preferably C30, especially D6 to D30. As already mentioned, the use of these homeopathic remedies increases the body's defense.

According to a further particular embodiment of the invention, witch hazel is included as an admixture in homeopathic form in aqueous solution in the dose D6 to D12. Hamamelis has anti-inflammatory, antioxidant and antiallergic properties. All of these properties increase the well-being of humans, especially in stressful situations.

According to one embodiment of the invention, at least one liquid stabilizer such as nitrogen or carbon dioxide is introduced into the drinking solution. Nitrogen is used in a laminate-coated container, wherein a nitrogen blanketing and pressure neutrality is provided. When nitrogen is injected, an overpressure of 0.5 to 1 bar is provided. The advantage of nitrogen is that it reduces the oxygen content, which improves the shelf life of the vitamins. Of course, carbon dioxide could also be used. It will bring about 0, 1 to 5.5 g / l, preferably 2-3 g / l bring.

According to a further development, a preservative is included. The durability can be selected or extended accordingly.

The object of the invention is also to provide a process for preparing a drug mixture that can be taken preventively as a drink or as a functional beverage before long or long trips, such as long-haul flights, but also train, bus or car trips or sedentary activity. to prevent impairment of physical well-being or possible venous injuries.

This object is also achieved by the invention.

The process according to the invention is characterized in that at least one active substance according to claim 1 is admixed with at least one further additional substance according to the above claims, for example a mineral and / or a vitamin, and that this mixture, in particular this powder mixture, preferably immediately before ingestion, in a solvent, in particular in an alcoholic and / or alcohol-free solvent, for example water, fruit juice or tea, in solution or to a suspension suspension and / or to a true solution.

With this functional drinking solution produced from the active substance mixture it is for the first time possible to prevent impairments on the basis of an expected poorer blood circulation as a preventative measure. The abovementioned active substances, in particular in the indicated dose, have an effect in particular In view of the perfusion function throughout the human body positively. This not only improves blood circulation in the extremities, especially in the legs, but also improves the circulation of the ginkgo flavonoids. In order to bring this mixture immediately before taking in a solvent, in particular in an alcohol-free solvent, for example water, fruit juice or tea in solution, known per se containers are used. Such a container that is well suited, for example, from WO 03/059774 A2 known.

The invention will be explained in more detail with reference to examples:

1 . Example:

Solvent: 1 l of water Active Ingredient: 75 mg of water-soluble aescin

Other substances: 100 mg magnesium

300 mg ascorbic acid 20 g glucose or 100 g maltodextrin

This drink solution prevents swelling and inflammation and helps to improve the blood flow microcirculatory.

2nd example

Solvent: 1 liter of water

Active ingredient: 500 mg Diosmin

Other substances: 300 mg ascorbic acid

300 mg Magnesium Flavoring: 2.5 g pineapple flavor

Homeopathic remedy: D9 Hamamelis

Food coloring: 3 g beta carotene

Fluid stabilization: overlay with nitrogen This hydration solution prevents swelling and inflammation and also improves microcirculation.

The flavor of the pineapple aroma comes into its own and has a fruity appearance.

3rd example

_Solvent:. 1 l of water Active ingredient: 75 mg aescin

Other substances: 300 mg ascorbic acid

100 mg of magnesium

Flavor: 1 g lemon flavor

Sweetener: acesulfame corresponding to 5 g of sugar

This drink solution prevents swelling and inflammation and contributes to

Improvement of microcirculation.

Light lemon flavor.

4th example

Solvent: 1 liter of water

Active substance: 600 mg of rutoside in the form of troxerutin

(water-soluble powder form) Other substances: 100 mg ascorbic acid

This drink solution prevents swelling and inflammation, helps to improve microcirculation.

It also has a moderate antiallergic effect. Sugar-free, tasteless drink solution.

5th example Solvent: 1 I cassis fruit juice or blue grape or

Raspberry active ingredient: 120 mg hesperidin

Other substances: 200 mg magnesium

Homeopathic remedy: C30 arnica

This drinking solution increases the protection against swelling and also protects against inflammation.

6th example

Solvent: 1 liter of aromatic black tea

Active ingredient: 500 mg red vine leaves. Other substances: 200 mg magnesium

Flavor: 2.5 g cherry or tangerine flavor

Sweetener: Cane sugar equivalent to 5 g of sugar

Of the above-indicated Examples 1 to 6 could of course be prepared with the indicated mixing ratio and without solvent in tablets or dragee form.

7. Example:

Solvent: 0.93 I Water Active ingredient: 40 mg Vitis viniferae

10 mg troxerutin

Other substances: 60 g fructose

1.5 g of potassium 5 g of citric acid 750 mg of ascorbic acid

0.6 g of flavorings

8. Example: Solvent 0.95 l of water

Substance 80 mg Vitis viniferae

20 mg troxerutin

Other substances 60 g fructose 1, 5 g potassium

5 g Citric Acid 150 mg Ascorbic acid 0.6 g Flavoring 2 g carbon dioxide

Examples 7 and 8 are drug mixtures which may optionally be marketed as nutritional supplements. As already mentioned, the requirements of a dietary enterality are in the sense of veno-antagonizing, oestusting, edema-protective, edema-reducing and / or vascular-occlusive, venous congestion-inhibiting and / or or to see endothelial stabilizing and / or anti-inflammatory and / or antioxidative (antiaging) properties

Of course, the examples 7 or 8 could be prepared with the indicated mixing ratio and without solvent in tablets or dragee foam

These potions generally provide protection against adverse effects on the vascular system in the microcirculatory area. They may require the normalization of vascular permeability. This results in reduced extravasation of plasma, proteins, or water into the vessel surrounding interstitial tissues

Finally, the benefits of the inventive means for the travel thrombosis prophylaxis are again summarized Traveling thrombosis prophylaxis is medically recommended not only for people with moderate and severe risk of thrombosis, but also for people with a low or apparently largely healthy vascular system. In the aircraft, the circulatory system, in particular the leg vein system is loaded by

• the air pressure, which corresponds approximately to a pressure in 11 000 ft (feet)

• Damp-proof cabins - Air due to the high compression of the air to 1 1 000 ft

• the extensive immobility of the leg joints (ankles, knees, hips) • the angled legs (knees, hip joints)

On long bus and train journeys, the burden may be lower, yet the circulatory system also suffers from such travel.

Therefore, the first basic measure recommended is:

• Physical activity in everyday life in the fresh air

• If possible, some leg-gymnastics while traveling or sitting

• Drinking of non-alcoholic drinking solutions according to the invention

• 6 at the latest 2 days before resumption begins with preventive measures

In phases of special stress, including occupational medical stress, such as long sitting with angled legs or long standing, it is recommended:

Regular drinking of small quantities of alcohol-free invention

Drinking solutions distributed throughout the day, about 1 1/2 liters in total.

• if possible, some leg-gymnastics.

Claims

claims

1. Wirkst off mixture, in particular active ingredient mixture for preventive health, containing at least one active ingredient, which is present in powdered and / or granulated form and / or as a mother tincture and / or as a pure substance and / or as an extract, from the group of capillary active, microcirculatory effective phytopharmacological active ingredients, preferably a flavonoid and / or a modified flavonoid, characterized in that in a maximum daily dose of a finished product at least one of the following active ingredients

Aescin at a dose of 0.1 to 150 mg, preferably 1.5 to 25 mg, in particular 5 to 20 mg,

Rutoside at a dose of 0.1 to 800 mg, preferably 1, 5 to 75 mg, in particular 5 to 25 mg,

Troxerutin at a dose of 0.1 to 300 mg, preferably 5 to 75 mg, in particular 5 to 30 mg,

Diosmin with a dose of 0.1 to 600 mg, preferably 1, 5 to 300 mg, in particular 5 to 30 mg, hesperidin with a dose of 0.1 to 100 mg, preferably 1, 5 to 50 mg, especially 5 to 30 mg,

Vitis viniferae (red wine) at a dose of 0.1 to 720 mg, preferably 35 to 500 mg, especially 5 to 150 mg, and / or

Ruscus aculeatus (butcher's broom) at a dose of 0, 1 to 45'0 mg, preferably

1, 5 to 100, in particular 5 to 50 mg is contained.

2. Active ingredient mixture according to claim 1, characterized in that at least one vitamin, such as ascorbic acid with a dose of 30 to 1 000 mg, preferably 60 to 200 mg is included.

3. Active substance mixture according to claim 1 or 2, characterized in that at least citric acid and / or salts thereof at a dose of 1 to 10 g, preferably 4 to 6 g is contained.

4. Active ingredient mixture according to one of the preceding claims 1 to 3, characterized in that at least one flavoring agent is contained at a dose of 0.1 to 20 g / l.

5. Active substance mixture according to one of the preceding claims 1 to 4, characterized in that at least one flavoring agent, in particular a natural flavoring agent such as lemon, lime, blackcurrant, blueberry, cherry, orange, mandarin, grapefruit -, almond, pineapple, blue grape, white grape juice, elderberry, strawberry, sea buckthorn flavor or citrus flavoring with a dose of 50 to 1 000mg, preferably 200 to 700 mg.

6. Active ingredient mixture according to one of the preceding claims 1 to 5, characterized in that at least one additive, preferably a silicate or a silicon dioxide and / or a binder, such as cellulose fibers, is included.

7. Active ingredient mixture according to one of the preceding claims 1 to 6, characterized in that at least one trace element or mineral, such as magnesium, calcium, potassium or sodium, with a dose of 10 to 2,000 mg, preferably 200 to 500 mg is.

8. Active ingredient mixture according to one of the preceding claims 1 to 7, characterized in that at least one amino acid with a dose of 0.01 to 200 mg, preferably 1 to 20 mg, is included.

9. Active substance mixture according to one of the preceding claims 1 to 8, characterized in that at least one food colorant, in particular a natural food dye such as quinoline yellow, beta carotene or yellow orange "S".

10. Active ingredient mixture according to one of the preceding claims 1 to 9, characterized in that at least one sweetener, such as saccharin sodium, sodium cyclamate, glucose, glucose, aspartame, dextrose, maltodextrin, sorbitol, xylitol, acesulfame, cane sugar, inulin or fructose, is included.

11. Active ingredient mixture according to one of the preceding claims 1 to 10, characterized in that at least one active ingredient according to claim 1 is contained with a dose corresponding to the requirements of a dietary supplement.

12. Active ingredient mixture according to one of the preceding claims 1 to 1 1, characterized in that the finished product as extract mixture and / or as a functional beverage and / or dragee (s) and / or as a tablet (s) and / or as granules and / or as effervescent powder and / or as syrup and / or as a drinking concentrate and / or as Aufschwemmlösung and / or as chewing gum and / or as a two-phase packing.

13. active substance mixture according to one of the preceding claims 1 to 12, characterized in that for the finished product as solvent, an alcoholic or alcohol-free solvent, for example water, fruit juice, tea, mineral water o. The like. Is used.

14. Active ingredient mixture according to one of the preceding claims 1 to 10 and 12 or 13, characterized in that at least one homeopathic agent, such as Lachesis and / or arnica and / or escin and / or rutin and / or rutoside and / or diosmin and / or Hamamelis and / or gingko and / or hesperidin and or red vine leaves.

15. Active ingredient mixture according to one of the preceding claims 1 to 10 and 12 to 14, characterized in that at least one of the active ingredients aescin and / or rutoside and / or diosmin and / or gingko and / or hesperidin and or red vine leaves as an admixture in homeopathic form in aqueous solution in the dose C20 to C40, preferably C30, in particular D6 to D30.

16. Active ingredient mixture according to one of the preceding claims 1 to 10 and 12 to 15, characterized in that Hamamelis is included as an admixture in homeopathic form in aqueous solution in the dose D6 to D12.

17. Active ingredient mixture according to one of the preceding claims 1 to 16, characterized in that in the drinking solution at least one liquid stabilizer such as nitrogen or carbon dioxide, is introduced.

18. Active ingredient mixture according to one of the preceding claims 1 to 17, characterized in that a preservative is included.

19. A process for preparing a drug mixture according to any one of the preceding claims 1 to 18, characterized in that at least one active ingredient according to claim 1, at least one further additional substance according to the above claims, for example a mineral and / or a vitamin, is admixed and that this Mixture, in particular this powder mixture, preferably immediately before ingestion, in one

Solvent, in particular in an alcoholic and / or alcohol-free solvent, for example water, fruit juice or tea, in solution or to a suspension suspension and / or brought to a true solution.