CA2551787C - Composition for the treatment of chronic venous insufficiencies comprising an extract of red vine leaves and an anti-inflammatory agent - Google Patents
Composition for the treatment of chronic venous insufficiencies comprising an extract of red vine leaves and an anti-inflammatory agent Download PDFInfo
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- CA2551787C CA2551787C CA2551787A CA2551787A CA2551787C CA 2551787 C CA2551787 C CA 2551787C CA 2551787 A CA2551787 A CA 2551787A CA 2551787 A CA2551787 A CA 2551787A CA 2551787 C CA2551787 C CA 2551787C
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
This invention relates to a new composition containing the effective concentration of an aqueous extract of red vine leaves (1) and an anti-inflammatory agent (2) for preventing or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs. The compositions according to this invention may also contain pharmaceutically or cosmically acceptable additives.
Description
COMPOSITION FOR THE TREATMENT OF CHRONIC VENOUS
INSUFFICIENCIES COMPRISING AN EXTRACT OF RED VINE LEAVES
AND AN ANTI-INFLAMMATORY AGENT
BACK-GROUND OF THE INVENTION
1. Technical Field The invention relates to compositions comprising an effective dose of an aqueous extract of red vine leaves and an anti-inflammatory agent for preventing or alleviating mild-to-moderate chronic venous insufficiency of the legs. The composition according to this invention also includes acceptable pharmaceutical or cosmetic additives. In addition, the compositions according to this inventions decrease or prevent subjective symptoms such as lassitude (listlessness), heavy legs, tired legs, sensation of tension, and pain associated with swelling of calves and ankles due to disorder of leg venous flow.
INSUFFICIENCIES COMPRISING AN EXTRACT OF RED VINE LEAVES
AND AN ANTI-INFLAMMATORY AGENT
BACK-GROUND OF THE INVENTION
1. Technical Field The invention relates to compositions comprising an effective dose of an aqueous extract of red vine leaves and an anti-inflammatory agent for preventing or alleviating mild-to-moderate chronic venous insufficiency of the legs. The composition according to this invention also includes acceptable pharmaceutical or cosmetic additives. In addition, the compositions according to this inventions decrease or prevent subjective symptoms such as lassitude (listlessness), heavy legs, tired legs, sensation of tension, and pain associated with swelling of calves and ankles due to disorder of leg venous flow.
2. Related Art Presently, there are millions of people around the world who suffer from mild-to-moderate chronic venous insufficiency of the legs. This common condition is characterized by an inadequacy of the venous circulation to return blood from the legs to the heart. The lack of adequate venous return results in venous stasis and an increased pressure within the venous circulation, promoting the development of oedema and tissular water retention.
Chronic venous insufficiency (CVI) is a functional disorder caused by persistent inadequacy of the venous return and is characterized clinically by oedema, skin changes and subjective complaints such as tired, heavy legs, pain or tingling sensations, which are typically amplified by standing upright and by high ambient temperatures. This dysfunction may be a source of major distress with a significant negative impact on the patient's overall well-being and quality of life.
Early stages (grade I) are characterized by coronal phlebectasia paraplantaris, subfascial congestion and oedema; grade II CVI is associated with low-grade skin changes, eczema and lipodeiniatosclerosis. If untreated, grades I and II often progress to an advanced stage characterized by recurrent venous leg ulcers (grade III). The stress caused by the symptoms, even when relatively mild initially, and the risk of later complications call for appropriate supportive and preventive measures to be initiated in the early stages of CVI.
Although some patients, even at early stages, might require surgery (sclerotherapy and variceal surgery), the use of compression stockings with or without additional physiotherapy is the most common treatment approach. The effect of compression is merely mechanical, i.e. this approach does not affect or correct the related biological dysfunction (capillary fragility in particular). Furthermore, the treatment with compression stockings often lacks compliance because of cosmetic concerns and the overall inconvenience of the compressive stockings, in the summer in particular. Therefore there is an urgent need for alternative approaches that are effective, well-tolerated and more convenient.
This extract of red vine leaves contains Rayon (ol) -glycosides, -glucuronides and flavonoids, with quercetin-3-0-beta-D-glucuronide and isoquercitrin (quercetin-3-0-beta-glucoside) as its main active ingredients. The range of their pharmacological actions has not yet been fully elucidated, but in-vitro studies indicate that they have antioxidant and anti-inflammatory properties and that they inhibit platelet aggregation and hyaluronidase and reduce oedema, possibly by reducing capillary permeability. Preclinical in-vivo experiments demonstrated anti-inflammatory and capillary wall thickening effects.
Dietary supplements including an aqueous extract of red vine leaves are disclosed to prevent and reduce the discomfort relating to mild-to-moderate chronic venous insufficiency of the legs in WO 01/28363. However, there are no hints to compositions comprising an aqueous extract of red vine leaves and other active ingredients such as anti-inflammatory agents given by WO 01/28363.
The German utility model DE 202 09 650 discloses a recipe of an aqueous balm for the care of legs of persons having venous discomfort comprising an extract of red vine leaves, Aloe Vera, extracts of Calendulae and horse chestnut, lavender oil, vitamins, and other ingredients.
However, there is no hint to the prevention and reduction the discomfort relating to mild-to-moderate chronic venous insufficiency of the legs.
SHORT DESCRIPTION OF THE INVENTION
Surprisingly, potentiation of anti-inflammatory and anti-oedematous action, index of pharmacological activities of an aqueous extract of red vine leaves, is found by combination of an anti-inflammatory agent with an aqueous extract of red vine leaves comparing the action itself. Moreover, composing mild anti-inflammatory agents resulted in safe compositions whose efficacy is potentiated for preventing and alleviating discomfort relating to mild-to-moderate chronic venous insufficiency of the legs with minimum or no adverse reactions.
The new compositions comprising an anti-inflammatory agent and an aqueous extract of red vine leaves potentiate the efficacy of prevention or relaxation for mild-to-moderate chronic venous insufficiency of the legs.
Therefore, this invention relates to new external compositions that comprise an effective dose of an aqueous extract of red vine leaves and an anti-inflammatory agent as pharmacological active substances and their efficacies are potentiated for preventing and relaxing mild-to-moderate chronic venous insufficiency of the legs.
OBJECTIVE OF THE PRESENT INVENTION
A primary objective of this invention provides more effective external compositions for preventing and alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
A further objective of this invention provides more effective external compositions including herb components and an anti-inflammatory agent. The herb components were manufactured pursuant to a controlled process that preserves the herbal effectiveness of the ingredients for preventing and/or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
Another objective of this invention provides more effective external compositions including herb components and an anti-inflammatory agent with minimum or no adverse event for safety of topical administration that prevent and/or alleviate the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
The other objective of this invention provides more effective external pharmaceutical compositions and more effective external medicated cosmetic compositions for preventing and/or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to external compositions for preventing or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs including an effective dose of an aqueous extract of red vine leaves and an anti-inflammatory agent.
The external composition of this invention consists of herbal ingredients derived from an aqueous extraction (Extractum vitis viniferae e folium spissum et siccum) of red vine leaves Voila vitis viniferae) and an anti-inflammatory agent.
The primary active ingredient of the external composition is the aqueous extract of red vine leaves (foliae vitis viniferae L.).
The teini "aqueous extract of red vine leaves" in this invention means the aqueous or solid aqueous extract of red vine leaves manufactured pursuant to a controlled process that preserves the herbal effectiveness of the ingredients. The term "dried extract of red vine leaves" in this invention means dried pure extract of the above aqueous extract of red vine leaves. The term "soft extract of red vine leaves" in this invention means soft extracts which is concentrated from 5 - 7 part of red vine leaves to one part. The term "liquid extract of red vine leaves" in this invention means liquid extracts which is prepared by resolving of soft extract of red vine leaves with solvent (60(VN)% ethanol / water) by the ratio of 1: 1.
Red vine leaves as starting material for the aqueous extract of red vine leaves in this invention is also known as "dyer" which are leaves of vitis vinifera LINNE with blackish-blue pericarp and a red pulp. Concentration of each polyphenol compound in red vine leaves and its composition are affected by various ecophysiological factors around. It is preferred that dried leaves of red vine containing at least 4 % of total polyphenols and 0.2 % of anthocyans are used as starting material in this invention. Red vine leaves characterized like those are harvested at a point of time where the content of flavonoids has reached an optimum i.e.
around the harvesting time of the grapes. Moreover, less than 15 cm length and less than 12 cm width of red vine leaves are preferable. The leaves are carefully dried and crushed. For extraction the leaves are cut to pieces of preferably 5 to 10 mm. To achieve a high content of flavonoids the extraction is done using purified water at elevated temperature, preferably at a temperature in the range of 60 to 80 C, over a time of at least 6 up to 10 hours. The preferred method is that of an exhaustive percolation.
The so-called fluid extract obtained in the process of the extraction may be directly used in the preparation of liquid dosage forms. In order to get a more concentrated extract, at least a part of the solvent is removed by use of a suitable evaporator preferably.
The thick extract is sterilized under heated-compressed condition, preferably at a temperature from 120 to 150 C for 1 up to 30 seconds, more preferably at a temperature from 140 to 145 C for 2 up to 5 seconds. The thick extract obtained in this step may again be directly used in the manufacturing of liquid dosage forms.
For the preparation of solid dosage foims the thick extract is dried, for instance by use of a vacuum drying oven or a vacuum drying conveyer. Carriers or excipients may be added during drying to facilitate further processing of the extract.
The aqueous extract of red vine leaves used in this invention by pure extract conversion of an aqueous extract of red vine leaves contains total flavonoids (quercetin-3-0-beta-D-glucuronide) preferably in the range of 0.625 to 25 %, more preferably in the range of 1.25 to 12.5 %, specially in the range of 2.5 to 10 %.
In the case of topical application, to prevent and/or alleviate the discomfort of mild-to-moderate chronic venous insufficiency of the legs, the amount of the aqueous extract of red vine leaves in equivalent quantity of soft extract of red vine leaves is between 0.1 and 20 g per 100 g (or 100 mL) of composition, preferably between 0.2 and 10 g per 100 g (or 100 mL) of composition, more preferably between 0.3 and 5 g per 100 g (or 100 mL) of composition, and further more preferably between 0.5 and 3 g per 100 g (or 100 mL) of composition.
The amount of the aqueous extract of red vine leaves in equivalent quantity of liquid extract of red vine leaves is between 0.2 and 40 g per 100 g (or 100 mL) of composition, preferably between 0.4 and 20 g per 100 g (or 100 mL) of composition, more preferably between 0.6 and g per 100 g (or 100 mL) of composition, and further more preferably between 1 and 6 g per 100 g (or 100 mL) of composition.
The compositions according to this invention include anti-inflammatory agents as second 5 active ingredients in addition to above aqueous extract of red vine leaves, provided that Aloe Vera, extracts of horse chestnut and Calendulae spp. and/or lavender oil are excluded.
Anti-inflammatory agents used in this invention are not limited and determined if the agents contain anti-inflammatory action, however, for safety of this agent with minimum or no 10 adverse event, anti-inflammatory agents with mild effects used in non-prescription drug, medicated cosmetics and cosmetics field for many years are preferable. In addition, types and dosage of anti-inflammatory agents change depending on whether this external composition is pharmaceutical products, medicated cosmetic product or cosmetic product.
Examples of such anti-inflammatory agents are non-steroidal anti-inflammatory drugs (NSAlDs), heparinoid, capsaicin, zinc oxide, glycyrrhizic acid and its salts thereof, glycyrrhetic acid and its salts and derivatives thereof, allantoin and its derivatives thereof, hyaluronic acid and its salts thereof, azulene and its salts and derivatives thereof, crude drugs and herbs having the anti-inflammatory action, and etc.. These anti-inflammatory agents can be used in one or mixed with more than two kinds.
Examples of such non-steroidal anti-inflammatory drugs are salicylic acid, methyl salicylate, glycol salicylate, ethylene glycol salicylate, indometacin, diclofenac, piroxicam, ketoprofen, felbinac, bufexamac, ufenamate, ibuprofen piconol, flurbiprofen and etc..
Examples of such glycyrrhizic acid and its salts thereof are glycyrrhizic acid, dipotassium glycyrrhizinate, monopotassium glycyrrhizinate, trisodium glycyrrhizinate, monoammonium glycyrrhizinate, ammonium glycyrrhizinate and etc..
Examples of such glycyrrhetic acid and its salts and derivatives thereof are glycyrrhetic acid, stearyl glycyrrhetinate, beta-glycyrrhetinic acid, carbenoxolone disodium (disodium succinoyl glycyrrhetinate) and etc..
Chronic venous insufficiency (CVI) is a functional disorder caused by persistent inadequacy of the venous return and is characterized clinically by oedema, skin changes and subjective complaints such as tired, heavy legs, pain or tingling sensations, which are typically amplified by standing upright and by high ambient temperatures. This dysfunction may be a source of major distress with a significant negative impact on the patient's overall well-being and quality of life.
Early stages (grade I) are characterized by coronal phlebectasia paraplantaris, subfascial congestion and oedema; grade II CVI is associated with low-grade skin changes, eczema and lipodeiniatosclerosis. If untreated, grades I and II often progress to an advanced stage characterized by recurrent venous leg ulcers (grade III). The stress caused by the symptoms, even when relatively mild initially, and the risk of later complications call for appropriate supportive and preventive measures to be initiated in the early stages of CVI.
Although some patients, even at early stages, might require surgery (sclerotherapy and variceal surgery), the use of compression stockings with or without additional physiotherapy is the most common treatment approach. The effect of compression is merely mechanical, i.e. this approach does not affect or correct the related biological dysfunction (capillary fragility in particular). Furthermore, the treatment with compression stockings often lacks compliance because of cosmetic concerns and the overall inconvenience of the compressive stockings, in the summer in particular. Therefore there is an urgent need for alternative approaches that are effective, well-tolerated and more convenient.
This extract of red vine leaves contains Rayon (ol) -glycosides, -glucuronides and flavonoids, with quercetin-3-0-beta-D-glucuronide and isoquercitrin (quercetin-3-0-beta-glucoside) as its main active ingredients. The range of their pharmacological actions has not yet been fully elucidated, but in-vitro studies indicate that they have antioxidant and anti-inflammatory properties and that they inhibit platelet aggregation and hyaluronidase and reduce oedema, possibly by reducing capillary permeability. Preclinical in-vivo experiments demonstrated anti-inflammatory and capillary wall thickening effects.
Dietary supplements including an aqueous extract of red vine leaves are disclosed to prevent and reduce the discomfort relating to mild-to-moderate chronic venous insufficiency of the legs in WO 01/28363. However, there are no hints to compositions comprising an aqueous extract of red vine leaves and other active ingredients such as anti-inflammatory agents given by WO 01/28363.
The German utility model DE 202 09 650 discloses a recipe of an aqueous balm for the care of legs of persons having venous discomfort comprising an extract of red vine leaves, Aloe Vera, extracts of Calendulae and horse chestnut, lavender oil, vitamins, and other ingredients.
However, there is no hint to the prevention and reduction the discomfort relating to mild-to-moderate chronic venous insufficiency of the legs.
SHORT DESCRIPTION OF THE INVENTION
Surprisingly, potentiation of anti-inflammatory and anti-oedematous action, index of pharmacological activities of an aqueous extract of red vine leaves, is found by combination of an anti-inflammatory agent with an aqueous extract of red vine leaves comparing the action itself. Moreover, composing mild anti-inflammatory agents resulted in safe compositions whose efficacy is potentiated for preventing and alleviating discomfort relating to mild-to-moderate chronic venous insufficiency of the legs with minimum or no adverse reactions.
The new compositions comprising an anti-inflammatory agent and an aqueous extract of red vine leaves potentiate the efficacy of prevention or relaxation for mild-to-moderate chronic venous insufficiency of the legs.
Therefore, this invention relates to new external compositions that comprise an effective dose of an aqueous extract of red vine leaves and an anti-inflammatory agent as pharmacological active substances and their efficacies are potentiated for preventing and relaxing mild-to-moderate chronic venous insufficiency of the legs.
OBJECTIVE OF THE PRESENT INVENTION
A primary objective of this invention provides more effective external compositions for preventing and alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
A further objective of this invention provides more effective external compositions including herb components and an anti-inflammatory agent. The herb components were manufactured pursuant to a controlled process that preserves the herbal effectiveness of the ingredients for preventing and/or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
Another objective of this invention provides more effective external compositions including herb components and an anti-inflammatory agent with minimum or no adverse event for safety of topical administration that prevent and/or alleviate the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
The other objective of this invention provides more effective external pharmaceutical compositions and more effective external medicated cosmetic compositions for preventing and/or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to external compositions for preventing or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs including an effective dose of an aqueous extract of red vine leaves and an anti-inflammatory agent.
The external composition of this invention consists of herbal ingredients derived from an aqueous extraction (Extractum vitis viniferae e folium spissum et siccum) of red vine leaves Voila vitis viniferae) and an anti-inflammatory agent.
The primary active ingredient of the external composition is the aqueous extract of red vine leaves (foliae vitis viniferae L.).
The teini "aqueous extract of red vine leaves" in this invention means the aqueous or solid aqueous extract of red vine leaves manufactured pursuant to a controlled process that preserves the herbal effectiveness of the ingredients. The term "dried extract of red vine leaves" in this invention means dried pure extract of the above aqueous extract of red vine leaves. The term "soft extract of red vine leaves" in this invention means soft extracts which is concentrated from 5 - 7 part of red vine leaves to one part. The term "liquid extract of red vine leaves" in this invention means liquid extracts which is prepared by resolving of soft extract of red vine leaves with solvent (60(VN)% ethanol / water) by the ratio of 1: 1.
Red vine leaves as starting material for the aqueous extract of red vine leaves in this invention is also known as "dyer" which are leaves of vitis vinifera LINNE with blackish-blue pericarp and a red pulp. Concentration of each polyphenol compound in red vine leaves and its composition are affected by various ecophysiological factors around. It is preferred that dried leaves of red vine containing at least 4 % of total polyphenols and 0.2 % of anthocyans are used as starting material in this invention. Red vine leaves characterized like those are harvested at a point of time where the content of flavonoids has reached an optimum i.e.
around the harvesting time of the grapes. Moreover, less than 15 cm length and less than 12 cm width of red vine leaves are preferable. The leaves are carefully dried and crushed. For extraction the leaves are cut to pieces of preferably 5 to 10 mm. To achieve a high content of flavonoids the extraction is done using purified water at elevated temperature, preferably at a temperature in the range of 60 to 80 C, over a time of at least 6 up to 10 hours. The preferred method is that of an exhaustive percolation.
The so-called fluid extract obtained in the process of the extraction may be directly used in the preparation of liquid dosage forms. In order to get a more concentrated extract, at least a part of the solvent is removed by use of a suitable evaporator preferably.
The thick extract is sterilized under heated-compressed condition, preferably at a temperature from 120 to 150 C for 1 up to 30 seconds, more preferably at a temperature from 140 to 145 C for 2 up to 5 seconds. The thick extract obtained in this step may again be directly used in the manufacturing of liquid dosage forms.
For the preparation of solid dosage foims the thick extract is dried, for instance by use of a vacuum drying oven or a vacuum drying conveyer. Carriers or excipients may be added during drying to facilitate further processing of the extract.
The aqueous extract of red vine leaves used in this invention by pure extract conversion of an aqueous extract of red vine leaves contains total flavonoids (quercetin-3-0-beta-D-glucuronide) preferably in the range of 0.625 to 25 %, more preferably in the range of 1.25 to 12.5 %, specially in the range of 2.5 to 10 %.
In the case of topical application, to prevent and/or alleviate the discomfort of mild-to-moderate chronic venous insufficiency of the legs, the amount of the aqueous extract of red vine leaves in equivalent quantity of soft extract of red vine leaves is between 0.1 and 20 g per 100 g (or 100 mL) of composition, preferably between 0.2 and 10 g per 100 g (or 100 mL) of composition, more preferably between 0.3 and 5 g per 100 g (or 100 mL) of composition, and further more preferably between 0.5 and 3 g per 100 g (or 100 mL) of composition.
The amount of the aqueous extract of red vine leaves in equivalent quantity of liquid extract of red vine leaves is between 0.2 and 40 g per 100 g (or 100 mL) of composition, preferably between 0.4 and 20 g per 100 g (or 100 mL) of composition, more preferably between 0.6 and g per 100 g (or 100 mL) of composition, and further more preferably between 1 and 6 g per 100 g (or 100 mL) of composition.
The compositions according to this invention include anti-inflammatory agents as second 5 active ingredients in addition to above aqueous extract of red vine leaves, provided that Aloe Vera, extracts of horse chestnut and Calendulae spp. and/or lavender oil are excluded.
Anti-inflammatory agents used in this invention are not limited and determined if the agents contain anti-inflammatory action, however, for safety of this agent with minimum or no 10 adverse event, anti-inflammatory agents with mild effects used in non-prescription drug, medicated cosmetics and cosmetics field for many years are preferable. In addition, types and dosage of anti-inflammatory agents change depending on whether this external composition is pharmaceutical products, medicated cosmetic product or cosmetic product.
Examples of such anti-inflammatory agents are non-steroidal anti-inflammatory drugs (NSAlDs), heparinoid, capsaicin, zinc oxide, glycyrrhizic acid and its salts thereof, glycyrrhetic acid and its salts and derivatives thereof, allantoin and its derivatives thereof, hyaluronic acid and its salts thereof, azulene and its salts and derivatives thereof, crude drugs and herbs having the anti-inflammatory action, and etc.. These anti-inflammatory agents can be used in one or mixed with more than two kinds.
Examples of such non-steroidal anti-inflammatory drugs are salicylic acid, methyl salicylate, glycol salicylate, ethylene glycol salicylate, indometacin, diclofenac, piroxicam, ketoprofen, felbinac, bufexamac, ufenamate, ibuprofen piconol, flurbiprofen and etc..
Examples of such glycyrrhizic acid and its salts thereof are glycyrrhizic acid, dipotassium glycyrrhizinate, monopotassium glycyrrhizinate, trisodium glycyrrhizinate, monoammonium glycyrrhizinate, ammonium glycyrrhizinate and etc..
Examples of such glycyrrhetic acid and its salts and derivatives thereof are glycyrrhetic acid, stearyl glycyrrhetinate, beta-glycyrrhetinic acid, carbenoxolone disodium (disodium succinoyl glycyrrhetinate) and etc..
Examples of such allantoin and its derivatives thereof are allantoin, aluminum chlorohydroxy allantoinate (alcloxa) and etc..
Examples of such hyaluronic acid and its salts thereof are hyaluronic acid, hyaluronate sodium and etc..
Examples of such azulene and its salts and derivatives thereof are azulene, guaiazulene (1,4-dimethy1-7-isopropylazulene), azulene sulfonate sodium, sodium guaiazulene sulfonate and etc..
Examples of such crude drugs and herbs having the anti-inflammatory action are turmeric (Curcumae rhizome), scutellaria root (Scutellariae radix), phellodendron bark (Phellodendri cortex), ginseng (Ginseng radix), coptis rhizome (Coptidis rhizoma), glycyrrhiza (Glycyrrhizae radix), cinnamon bark (Cinnarnomi cortex), gentian (Gentianae radix), safflower (Carthami Flos), gardenia fruit (Gardeniae fructus), lithospermum root (Lithospermi radix), peony root (Paeoniae radix), ginger (Zingiberis Rhizoma), swertia herb (Swertia japonica), mulberry bark (Mori cortex), rhubarb (Rhei rhizoma), Japanese angelica root (Angelicae radix), capsicum (Capsici fructus), atractylodes rhizome (Atractylodis rhizoma), poria sclerotium (Poria), hydrangea (Hydrangea serrata Seringe var), comfrey (Symphytum officiale), arnica (Arnica montana), ginko (Ginko biloba), St.
John's wort (Hypericum petforcztutn), purple deadnettle (Latnium putpureum L.), olive(0/ea europaea) leaves, German chamomile (Chamomilla recutita), fragrant wormwood (Artemisia capillaris), gardenia (Gardenia jasminoides), tall groundcover (Sasa veitchii), perilla (Perilla frutescens var crispa), linden (Tilia cordata Mill.), white birch (Betula platyphylla var japonica) bark, horsetail (Equisetum arvense), ground ivy (Hedera helix), sage (Salvia officnalis), mallow (Malva sylvestris), clove (Pimenta syzygium), calendula (Calendula officinalis L.), Houttuynia (Houttuynia cordata Thunberg), loquat (Eriobotrya japonica Lindl.) leaf, loofah (Luffa cylindrica), tree peony (Paeonia suffruticosa), pine (Pinus sylyestris L.) cone, house chestnut (Aesculus hippocastanum L.), mukurossi peel (Spindus mukurossi), peach (Prunus persica) leaf, cornflower (centaurea cyanuns L.), saxifrage (Saxifraga stolonifera), wormwood (Artemisia princeps Pampan), rosemary (Rosemarinus officinalis L.), chamomile (Anthemis Nobilis), burnet (Sanguisorbae officinalis L.), zanthoxvlum fruit (Zanthoxyli fructus), chamomile flower (Chamomilla recutitaflos), camphor (Cinnamomuni camphora), devil's claw (Harpagophytum procumbens), fir needle oil (Abies sibirica), hay flower (Graminis flay), pine needle oil (Firms sylvestris), stinging nettle (Urtica dioica), white willow bark (Sal ix alba cortex), witch hazel (Hamamelis virginiana L.) and etc.. In addition, these crude drug and herb having anti-inflammatory action can be dried powder, extract, fluidextract, ctincture, oil and etc..
Combination amount of anti-inflammatory agent used in this invention components changes depending on types of anti-inflammatory agents and categorization as pharmaceutical products or medicated cosmetic products, but the amount of anti-inflammatory agent is usually between 0.0001 and 50 g per 100 g (or 100 mL) of composition.
Specifically, a combination amount of non-steroidal anti-inflammatory drugs is preferably between 0.01 and 50 g per 100 g (or 100 mL) of composition, more preferably between 0.03 and 20 g per 100 g (or 100 mL) of composition, further more preferably between 0.05 and 10 g per 100 g (or 100 mL) of composition.
A combination amount of heparinoid is preferably between 0.01 and 1 g per 100 g (or 100 mL) of composition, more preferably between 0.02 and 0.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.03 and 0.3 g per 100 g (or 100 mL) of composition.
A combination amount of capsaicin is preferably between 0.0001 and 1 g per 100 g (or 100 mL) of composition, more preferably between 0.0005 and 0.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.001 and 0.1 g per 100 g (or 100 mL) of composition.
A combination amount of zinc oxide is preferably between 0.001 and 60 g per 100 g (or 100 mL) of composition, more preferably between 0.01 and 20 g per 100 g (or 100 mL) of composition, further more preferably between 0.1 and 10 g per 100 g (or 100 mL) of composition.
A combination amount of glycyrrhizic acid and its salts thereof is preferably between 0.001 and 2 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 1.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 1 g per 100 g (or 100 mL) of composition.
A combination amount of glycyrrhetic acid and its salts and derivatives thereof is preferably between 0.001 and 3 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 2.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 2 g per 100 g (or 100 mL) of composition.
A combination amount of allantoin and its derivatives thereof is preferably between 0.001 and 10 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 5 g per 100 g (or 100 mL) of composition, further more preferably between 0.05 and 2 g per 100 g (or 100 mL) of composition.
A combination amount of hyaluronic acid and its salts thereof is preferably between 0.001 and 10 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 5 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 2 g per 100 g (or 100 mL) of composition.
A combination amount of lactoferrin is preferably between 0.001 and 5 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 3 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 1 g per 100 g (or 100 mL) of composition.
A combination amount of azulene and its salts and derivatives thereof is preferably between 0.001 and 0.4 g per 100 g (or 100 mL) of composition, more preferably between 0.01 and 0.3 g per 100 g (or 100 mL) of composition, further more preferably between 0.02 and 0.2 g per 100 g (or 100 mL) of composition.
A combination amount of crude drugs and herbs having the anti-inflammatory action is preferably between 0.001 and 50 g per 100 g (or 100 mL) of composition, preferably between 0.01 and 30 g per 100 g (or 100 mL) of composition, more preferably between 0.02 and 20 g per 100 g (or 100 mL) of composition.
Depending on dosage forms, the external composition of the present invention is applied directly onto the leg skin once or several times a day. And the composition may be massaged in thinly, starting from the foot and working up towards the thigh.
In addition to active ingredients mentioned above, the external compositions of the present invention may also include other active ingredients.
The external compositions described in the present invention can be used in any topical forms such as creams, ointments, gel ointments, plasters, tapes, topical solutions, aerosols, lotions, tinctures and the like. Any of these formulations may be prepared using regular methods.
And any additives in common use may be used upon preparation of these formulations, if necessary.
These external dosage forms described in the present invention may be prepared using regular methods by adding generally available pharmaceutical additives and cosmetic additives such as bases, excipients, binders, lubricants, superplasticizers, plasticizers, antifoaming agents, polish, foaming agents, antistatic agents, desiccant, moisturizing agents, surfactant, solubilizer, buffer agents, resolvents, solubilizing agents, solvents, diluents, stabilizers, emulsifying agents, suspension, suspending agents, dispersing agents, isotonizing agents, aerosol propellant, adsorbents, reducing agents, antioxidant, backing, wetting agents, wet modifier, filler, extender, adhesives, viscous agent, softeners, pH modifiers, antiseptics, preservatives, corrigent, refrigerative agents, flavoring agents, perfume, fragrance, coloring matters, and the like.
Examples of such additives are described in Japanese Pharmaceutical Excipients Directory 2000 (edited by japan Pharmaceutical Excipients Council, issued by Yakuji Nippo, Ltd.), The Japan's Specifications and Standards for Food Additives (issued by Japan Food Additives Association), Japanese Standards of Quasi-drug Ingredients (edited by Society of Japanese Pharmacopoeia, issued by Yakuji Nippo, Ltd.), Japan Cosmetic Ingredients Dictionary 4th Edition (edited by Japan Cosmetic Industry Association, issued by Yakuji Nippo, Ltd.), The Comprehensive Licensing Standards Of Cosmetics by Category (edited by Society of Japanese Pharmacopoeia, issued by Yakuji Nippo, Ltd.), The Japanese Cosmetic Ingredients Codex (edited and issued by Yakuji Nippo, Ltd.), International Cosmetic Ingredient Dictionary and Handbook Ninth Edition 2002 (edited by John A. Wenninger, issued by The Cosmetic Toiletry and Fragrance Association) and etc..
The compositions according to this invention can be provided as pharmaceutical products or medicated cosmic products. The compositions described in this invention are explained by the following practical examples. However, the scope of the claims should not be limited to these practical examples.
Examples Example 1 :Cream The following ingredients were processed through a regular method to form cream at the total weight of 1kg, added with sodium citrate to adjust at pH 5.5.
Soft extract of red vine leaves 28.2 g Dipotassium glycyrrhizinate 5.0 g Salicylic acid 4.0 g White petrolatum 50.0 g Stearyl alcohol 40.0 g Glyceryl monostearate 34.0 g Polyoxyethylene (25) cetylether 16.0 g Medium chain fatty acid triglyceride 120.0 g Propylene glycol 50.0 g Citric acid 0.1 g Sodium citrate Adequate amount Antiseptics Adequate amount Purified water Adequate amount - ha-Example 2 : Gel ointment The following ingredients were processed through a regular method to form gel ointments at the total weight of lkg, added with triethanolamine to adjust at pH 5.5.
Liquid extract of red vine leaves 12.5 g Glycyrrhetic acid 5.0 g Salicylic acid 4.0 g Allantoin 2.0 g Isopropanol 350.0 g Propylene glycol 50.0 g Carboxyvinyl polymer 20.0 g Triethanolamine Adequate amount Purified water Adequate amount Example 3 : Ointment The following ingredients were processed through a regular method to form ointments at the total weight of lkg.
Liquid extract of red vine leaves 12.5 g Methyl salicylate 5.0 g Glycyrrhizic acid 1.0 g Heparinoid 1.0 g Zinc oxide 1.0 g Sorbitan sesquioleate 5.0g Light liquid paraffin 50.0 g White petrolatum Adequate amount Example 4 : Plaster The following ingredients were processed through a regular method to form adhesive masse at the total weight of 1kg. The resulted adhesive masse was coated on the non-woven fabric to prepare the plasters.
Soft extract of red vine leaves 10.0 g Glycol salicylate 5.0 g Arnica tincture 5.0 g House chestnut extract 5.0 g Japanese angelica root extract 0.2 g Glycyrrhizic acid 0.2 g Capsicum extract 0.1 g Hyaluronate sodium 0.1 g Polyoxyethylene (9) lauryl ether 10.0 g L-menthol 5.0 g Propylene glycol 50.0 g Concentrated glycerin 150.0 g D-sorbitol solution 300.0 g Sodium polyacrylate 50.0 g Carbox ymethylcellulose sodium 20.0 g Eudragit E 100 0.5 g Kaolin 30.0 g Sodium edetate 0.5 g Dried aluminum potassium sulfate 5.0 g Tartaric acid 1.0 g Antiseptics Adequate amount Purified water Adequate amount
Examples of such hyaluronic acid and its salts thereof are hyaluronic acid, hyaluronate sodium and etc..
Examples of such azulene and its salts and derivatives thereof are azulene, guaiazulene (1,4-dimethy1-7-isopropylazulene), azulene sulfonate sodium, sodium guaiazulene sulfonate and etc..
Examples of such crude drugs and herbs having the anti-inflammatory action are turmeric (Curcumae rhizome), scutellaria root (Scutellariae radix), phellodendron bark (Phellodendri cortex), ginseng (Ginseng radix), coptis rhizome (Coptidis rhizoma), glycyrrhiza (Glycyrrhizae radix), cinnamon bark (Cinnarnomi cortex), gentian (Gentianae radix), safflower (Carthami Flos), gardenia fruit (Gardeniae fructus), lithospermum root (Lithospermi radix), peony root (Paeoniae radix), ginger (Zingiberis Rhizoma), swertia herb (Swertia japonica), mulberry bark (Mori cortex), rhubarb (Rhei rhizoma), Japanese angelica root (Angelicae radix), capsicum (Capsici fructus), atractylodes rhizome (Atractylodis rhizoma), poria sclerotium (Poria), hydrangea (Hydrangea serrata Seringe var), comfrey (Symphytum officiale), arnica (Arnica montana), ginko (Ginko biloba), St.
John's wort (Hypericum petforcztutn), purple deadnettle (Latnium putpureum L.), olive(0/ea europaea) leaves, German chamomile (Chamomilla recutita), fragrant wormwood (Artemisia capillaris), gardenia (Gardenia jasminoides), tall groundcover (Sasa veitchii), perilla (Perilla frutescens var crispa), linden (Tilia cordata Mill.), white birch (Betula platyphylla var japonica) bark, horsetail (Equisetum arvense), ground ivy (Hedera helix), sage (Salvia officnalis), mallow (Malva sylvestris), clove (Pimenta syzygium), calendula (Calendula officinalis L.), Houttuynia (Houttuynia cordata Thunberg), loquat (Eriobotrya japonica Lindl.) leaf, loofah (Luffa cylindrica), tree peony (Paeonia suffruticosa), pine (Pinus sylyestris L.) cone, house chestnut (Aesculus hippocastanum L.), mukurossi peel (Spindus mukurossi), peach (Prunus persica) leaf, cornflower (centaurea cyanuns L.), saxifrage (Saxifraga stolonifera), wormwood (Artemisia princeps Pampan), rosemary (Rosemarinus officinalis L.), chamomile (Anthemis Nobilis), burnet (Sanguisorbae officinalis L.), zanthoxvlum fruit (Zanthoxyli fructus), chamomile flower (Chamomilla recutitaflos), camphor (Cinnamomuni camphora), devil's claw (Harpagophytum procumbens), fir needle oil (Abies sibirica), hay flower (Graminis flay), pine needle oil (Firms sylvestris), stinging nettle (Urtica dioica), white willow bark (Sal ix alba cortex), witch hazel (Hamamelis virginiana L.) and etc.. In addition, these crude drug and herb having anti-inflammatory action can be dried powder, extract, fluidextract, ctincture, oil and etc..
Combination amount of anti-inflammatory agent used in this invention components changes depending on types of anti-inflammatory agents and categorization as pharmaceutical products or medicated cosmetic products, but the amount of anti-inflammatory agent is usually between 0.0001 and 50 g per 100 g (or 100 mL) of composition.
Specifically, a combination amount of non-steroidal anti-inflammatory drugs is preferably between 0.01 and 50 g per 100 g (or 100 mL) of composition, more preferably between 0.03 and 20 g per 100 g (or 100 mL) of composition, further more preferably between 0.05 and 10 g per 100 g (or 100 mL) of composition.
A combination amount of heparinoid is preferably between 0.01 and 1 g per 100 g (or 100 mL) of composition, more preferably between 0.02 and 0.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.03 and 0.3 g per 100 g (or 100 mL) of composition.
A combination amount of capsaicin is preferably between 0.0001 and 1 g per 100 g (or 100 mL) of composition, more preferably between 0.0005 and 0.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.001 and 0.1 g per 100 g (or 100 mL) of composition.
A combination amount of zinc oxide is preferably between 0.001 and 60 g per 100 g (or 100 mL) of composition, more preferably between 0.01 and 20 g per 100 g (or 100 mL) of composition, further more preferably between 0.1 and 10 g per 100 g (or 100 mL) of composition.
A combination amount of glycyrrhizic acid and its salts thereof is preferably between 0.001 and 2 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 1.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 1 g per 100 g (or 100 mL) of composition.
A combination amount of glycyrrhetic acid and its salts and derivatives thereof is preferably between 0.001 and 3 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 2.5 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 2 g per 100 g (or 100 mL) of composition.
A combination amount of allantoin and its derivatives thereof is preferably between 0.001 and 10 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 5 g per 100 g (or 100 mL) of composition, further more preferably between 0.05 and 2 g per 100 g (or 100 mL) of composition.
A combination amount of hyaluronic acid and its salts thereof is preferably between 0.001 and 10 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 5 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 2 g per 100 g (or 100 mL) of composition.
A combination amount of lactoferrin is preferably between 0.001 and 5 g per 100 g (or 100 mL) of composition, more preferably between 0.005 and 3 g per 100 g (or 100 mL) of composition, further more preferably between 0.01 and 1 g per 100 g (or 100 mL) of composition.
A combination amount of azulene and its salts and derivatives thereof is preferably between 0.001 and 0.4 g per 100 g (or 100 mL) of composition, more preferably between 0.01 and 0.3 g per 100 g (or 100 mL) of composition, further more preferably between 0.02 and 0.2 g per 100 g (or 100 mL) of composition.
A combination amount of crude drugs and herbs having the anti-inflammatory action is preferably between 0.001 and 50 g per 100 g (or 100 mL) of composition, preferably between 0.01 and 30 g per 100 g (or 100 mL) of composition, more preferably between 0.02 and 20 g per 100 g (or 100 mL) of composition.
Depending on dosage forms, the external composition of the present invention is applied directly onto the leg skin once or several times a day. And the composition may be massaged in thinly, starting from the foot and working up towards the thigh.
In addition to active ingredients mentioned above, the external compositions of the present invention may also include other active ingredients.
The external compositions described in the present invention can be used in any topical forms such as creams, ointments, gel ointments, plasters, tapes, topical solutions, aerosols, lotions, tinctures and the like. Any of these formulations may be prepared using regular methods.
And any additives in common use may be used upon preparation of these formulations, if necessary.
These external dosage forms described in the present invention may be prepared using regular methods by adding generally available pharmaceutical additives and cosmetic additives such as bases, excipients, binders, lubricants, superplasticizers, plasticizers, antifoaming agents, polish, foaming agents, antistatic agents, desiccant, moisturizing agents, surfactant, solubilizer, buffer agents, resolvents, solubilizing agents, solvents, diluents, stabilizers, emulsifying agents, suspension, suspending agents, dispersing agents, isotonizing agents, aerosol propellant, adsorbents, reducing agents, antioxidant, backing, wetting agents, wet modifier, filler, extender, adhesives, viscous agent, softeners, pH modifiers, antiseptics, preservatives, corrigent, refrigerative agents, flavoring agents, perfume, fragrance, coloring matters, and the like.
Examples of such additives are described in Japanese Pharmaceutical Excipients Directory 2000 (edited by japan Pharmaceutical Excipients Council, issued by Yakuji Nippo, Ltd.), The Japan's Specifications and Standards for Food Additives (issued by Japan Food Additives Association), Japanese Standards of Quasi-drug Ingredients (edited by Society of Japanese Pharmacopoeia, issued by Yakuji Nippo, Ltd.), Japan Cosmetic Ingredients Dictionary 4th Edition (edited by Japan Cosmetic Industry Association, issued by Yakuji Nippo, Ltd.), The Comprehensive Licensing Standards Of Cosmetics by Category (edited by Society of Japanese Pharmacopoeia, issued by Yakuji Nippo, Ltd.), The Japanese Cosmetic Ingredients Codex (edited and issued by Yakuji Nippo, Ltd.), International Cosmetic Ingredient Dictionary and Handbook Ninth Edition 2002 (edited by John A. Wenninger, issued by The Cosmetic Toiletry and Fragrance Association) and etc..
The compositions according to this invention can be provided as pharmaceutical products or medicated cosmic products. The compositions described in this invention are explained by the following practical examples. However, the scope of the claims should not be limited to these practical examples.
Examples Example 1 :Cream The following ingredients were processed through a regular method to form cream at the total weight of 1kg, added with sodium citrate to adjust at pH 5.5.
Soft extract of red vine leaves 28.2 g Dipotassium glycyrrhizinate 5.0 g Salicylic acid 4.0 g White petrolatum 50.0 g Stearyl alcohol 40.0 g Glyceryl monostearate 34.0 g Polyoxyethylene (25) cetylether 16.0 g Medium chain fatty acid triglyceride 120.0 g Propylene glycol 50.0 g Citric acid 0.1 g Sodium citrate Adequate amount Antiseptics Adequate amount Purified water Adequate amount - ha-Example 2 : Gel ointment The following ingredients were processed through a regular method to form gel ointments at the total weight of lkg, added with triethanolamine to adjust at pH 5.5.
Liquid extract of red vine leaves 12.5 g Glycyrrhetic acid 5.0 g Salicylic acid 4.0 g Allantoin 2.0 g Isopropanol 350.0 g Propylene glycol 50.0 g Carboxyvinyl polymer 20.0 g Triethanolamine Adequate amount Purified water Adequate amount Example 3 : Ointment The following ingredients were processed through a regular method to form ointments at the total weight of lkg.
Liquid extract of red vine leaves 12.5 g Methyl salicylate 5.0 g Glycyrrhizic acid 1.0 g Heparinoid 1.0 g Zinc oxide 1.0 g Sorbitan sesquioleate 5.0g Light liquid paraffin 50.0 g White petrolatum Adequate amount Example 4 : Plaster The following ingredients were processed through a regular method to form adhesive masse at the total weight of 1kg. The resulted adhesive masse was coated on the non-woven fabric to prepare the plasters.
Soft extract of red vine leaves 10.0 g Glycol salicylate 5.0 g Arnica tincture 5.0 g House chestnut extract 5.0 g Japanese angelica root extract 0.2 g Glycyrrhizic acid 0.2 g Capsicum extract 0.1 g Hyaluronate sodium 0.1 g Polyoxyethylene (9) lauryl ether 10.0 g L-menthol 5.0 g Propylene glycol 50.0 g Concentrated glycerin 150.0 g D-sorbitol solution 300.0 g Sodium polyacrylate 50.0 g Carbox ymethylcellulose sodium 20.0 g Eudragit E 100 0.5 g Kaolin 30.0 g Sodium edetate 0.5 g Dried aluminum potassium sulfate 5.0 g Tartaric acid 1.0 g Antiseptics Adequate amount Purified water Adequate amount
Claims (16)
1. A composition for the prevention, alleviation or prevention and alleviation of mild-to-moderate chronic venous insufficiency (CVI) of the legs comprising an aqueous extract of red vine leaves (1) and an anti-inflammatory agent (2) as pharmacologically active substances.
2. A composition according to claim 1 containing an aqueous extract of red vine leaves (1), which is obtained by extraction from dried red vine leaves containing at least 4 % of total polyphenols and at least 0.2 % of anthocyans using purified water.
3. A composition according to claim 1 or 2, which contains from 0.1 to 20g of soft extract of red vine leaves (1) per 100g or 100mL of total composition.
4. A composition according to claim 1 or 2, which contains from 0.2 to 10g of soft extract of red vine leaves (1) per 100g or 100mL of total composition.
5. A composition according to claim 1 or 2, which contains from 0.5 to 3g of soft extract of red vine leaves (1) per 100g or 100mL of total composition.
6. A composition according to any one of claims 1 to 5, which contains from 0.2 to 40g of liquid extract of red vine leaves (1) per 100g or 100mL of total composition.
7. A composition according to any one of claims 1 to 5, which contains from 0.4 to 20g of liquid extract of red vine leaves (1) per 100g or 100mL of total composition.
8. A composition according to any one of claims 1 to 5, which contains from 1 to 6g of liquid extract of red vine leaves (1) per 100g or 100mL of total composition.
9. A composition according to any one of claims 1 to 8, which contains from 0.625 to 25 % by weight of flavonoids in the dried aqueous extract of red vine leaves (1).
10. A composition according to any one of claims 1 to 8, which contains from 2.5 and 10 % by weight of flavonoids in the dried aqueous extract of red vine leaves (1).
11. A composition according to any one of claims 1 to 10, wherein the anti-inflammatory agent (2) is selected from the group consisting of non-steroidal anti-inflammatory drugs, heparinoid, capsaicin, zinc oxide, glycyrrhizic acid and its salts thereof, glycyrrhetic acid and its salts and derivatives thereof, allantoin and its derivatives thereof, hyaluronic acid and its salts thereof, azulene and its salts and derivatives thereof, crude drugs and herbs having the anti-inflammatory action and mixtures thereof.
12. A composition according to any one of claims 1 to 11, which contains 0.0001 to 50g per 100g or 100mL of total composition) of one or more anti-inflammatory agents (2).
13. A composition according to any one of claims 1 to 12, wherein the weight ratio between the dried aqueous extract of red vine leaves (1) to the anti-inflammatory agent (2) is from 1 to 500 to 400,000 to 1.
14. A composition according to any one of claims 1 to 13, which is for parenteral use.
15. A composition according to any one of claims 1 to 13, which is for external use.
16. Use of a composition as claimed in any one of claims 1 to 15 for the preparation of a pharmaceutical product or a medicated cosmetic product for the prevention, alleviation or prevention and alleviation of mild-to-moderate chronic venous insufficiency (CVI) of the legs.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04003705 | 2004-02-19 | ||
| EP04003705.3 | 2004-02-19 | ||
| PCT/EP2005/001424 WO2005079600A1 (en) | 2004-02-19 | 2005-02-12 | Composition for the treatment of chronic venous insufficiencies comprising an extract of red vine leaves and an anti-inflammatory agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2551787A1 CA2551787A1 (en) | 2005-09-01 |
| CA2551787C true CA2551787C (en) | 2014-04-08 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2551787A Active CA2551787C (en) | 2004-02-19 | 2005-02-12 | Composition for the treatment of chronic venous insufficiencies comprising an extract of red vine leaves and an anti-inflammatory agent |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7674488B2 (en) |
| EP (1) | EP1718168A1 (en) |
| JP (1) | JP2007523110A (en) |
| BR (1) | BRPI0507895A (en) |
| CA (1) | CA2551787C (en) |
| RU (1) | RU2367464C2 (en) |
| UA (1) | UA90668C2 (en) |
| WO (1) | WO2005079600A1 (en) |
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| DE20209650U1 (en) * | 2002-06-21 | 2002-09-12 | Sterken Brigitte | Vein Active Balm |
| US20040151794A1 (en) | 2002-12-31 | 2004-08-05 | Boehringer Ingelheim International Gmbh | Method of improvement of blood circulation |
| US20040151769A1 (en) | 2002-12-31 | 2004-08-05 | Boehringer Ingelheim International Gmbh | Film coated tablet containing an extract of red vine leaves |
| ES2346649T3 (en) | 2002-12-31 | 2010-10-19 | Boehringer Ingelheim International Gmbh | COMPRESSED COVERED WITH A FILM THAT INCLUDES AN EXTRACT OF RED PARRA LEAVES. |
| US20040146539A1 (en) * | 2003-01-24 | 2004-07-29 | Gupta Shyam K. | Topical Nutraceutical Compositions with Selective Body Slimming and Tone Firming Antiaging Benefits |
| US20040223962A1 (en) * | 2003-05-07 | 2004-11-11 | Riordan Neil H. | Method and composition for preventing or reducing edema, deep vein thrombosis and/or pulmonary embolism |
| EP1550450A1 (en) | 2003-12-29 | 2005-07-06 | Boehringer Ingelheim International GmbH | Composition comprising an aqueous extract of red vine leaves and a blood circulating-improving agent for the treatment of chronic venous insufficiencies |
| EP1550452A1 (en) | 2003-12-29 | 2005-07-06 | Boehringer Ingelheim International GmbH | Composition comprising an aqueous extract of red vine leaves and a antthrombotic agent for the treatment of chronic venous insufficiencies |
| EP1550451A1 (en) | 2003-12-29 | 2005-07-06 | Boehringer Ingelheim International GmbH | Composition comprising an aqueous extract of red vine leaves and a diuretic for the treatment of chronic venous insufficiencies |
| CA2551787C (en) | 2004-02-19 | 2014-04-08 | Boehringer Ingelheim International Gmbh | Composition for the treatment of chronic venous insufficiencies comprising an extract of red vine leaves and an anti-inflammatory agent |
-
2005
- 2005-02-12 CA CA2551787A patent/CA2551787C/en active Active
- 2005-02-12 JP JP2006553503A patent/JP2007523110A/en active Pending
- 2005-02-12 BR BRPI0507895-4A patent/BRPI0507895A/en not_active Application Discontinuation
- 2005-02-12 WO PCT/EP2005/001424 patent/WO2005079600A1/en active Application Filing
- 2005-02-12 RU RU2006133257/15A patent/RU2367464C2/en active
- 2005-02-12 EP EP05715312A patent/EP1718168A1/en not_active Ceased
- 2005-02-12 UA UAA200609880A patent/UA90668C2/en unknown
- 2005-02-18 US US11/061,556 patent/US7674488B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20050271757A1 (en) | 2005-12-08 |
| WO2005079600A1 (en) | 2005-09-01 |
| EP1718168A1 (en) | 2006-11-08 |
| US7674488B2 (en) | 2010-03-09 |
| CA2551787A1 (en) | 2005-09-01 |
| BRPI0507895A (en) | 2007-07-24 |
| JP2007523110A (en) | 2007-08-16 |
| UA90668C2 (en) | 2010-05-25 |
| RU2367464C2 (en) | 2009-09-20 |
| RU2006133257A (en) | 2008-03-27 |
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| EEER | Examination request |