Composition comprising an aqueous extract of red vine leaves and a diuretic for the treatment of chronic venous insufficiencies

BACK-GROUND OF THE INVENTION

1. Technical Field

0001The invention relates to compositions comprising an effective dose of an aqueous extract of red vine leaves and a diuretic for preventing or alleviating mild-to-moderate chronic venous insufficiency of the legs. The composition according to this invention also includes acceptable pharmaceutical or dietetic 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

0002Presently, 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.

0003Early 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 lipodermatosclerosis. 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.

0004Although 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.

0005This extract of red vine leaves contains flavon (ol) -glycosides, -glucuronides and flavonoids, with quercetin-3-O-beta-D-glucuronide and isoquercitrin (quercetin-3-O-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.

0006Dietary 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 diuretics given by WO 01/28363.

SHORT DESCRIPTION OF THE INVENTION

0007Surprisingly, potentiation of anti-inflammatory action and inhibitory action on oedema, indices of pharmacological activities of an aqueous extract of red vine leaves, is found by combination of a diuretic with an aqueous extract of red vine leaves comparing the action itself. Moreover, composing mild diuretics 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 a diuretic 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.

0008Therefore, this invention relates to new compositions that comprise an effective dose of an aqueous extract of red vine leaves and a diuretic as pharmacological active substances and their efficacies are potentiated for preventing and relaxing mild-to-moderate chronic venous insufficiency of the legs.

<i><u>Objective of the present invention</u></i>

0009A primary objective of this invention provides more effective internal compositions for preventing and alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.

0010A further objective of this invention provides more effective internal compositions including herb components and a diuretic. 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.

0011Another objective of this invention provides more effective internal compositions including herb components and a diuretic with minimum or no adverse event for safety of internal consumption that prevent and/or alleviate the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.

0012The other objective of this invention provides more effective internal pharmaceutical compositions and foods for preventing and/or alleviating the discomfort associated with mild-to-moderate chronic venous insufficiency of the legs.

DETAILED DESCRIPTION OF THE INVENTION

0013This invention relates to internal 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 a diuretic.

0014The internal composition of this invention consists of herbal ingredients derived from an extraction (<i>Extractum vitis viniferae e folium spissum et siccum</i>) of red vine leaves (<i>folia vitis viniferae</i>) and a diuretic.

0015The primary active ingredient of the internal composition is the aqueous extract of red vine leaves (<i>foliae vitis viniferae L.</i>). The term "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 "red vine leaves extract" in this invention means solid extracts added with silicon dioxide in the range of 1 to 10 (wt/wt)% (described as %) and glucose syrup (as dried material) in the range of 5 to 25 % to the above dried extract of red vine leaves (solid pure extracts) in the range of 70 to 90 %.

0016Red 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 <i>vitis vinifera</i> 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 forms 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.

0017The ratio of carriers or excipients in the range of 10 to 30 % and dried extract of red vine leaves (as pure extract) in the range of 70 to 90 % in red vine leaves extract is preferable. Such carriers or excipients exemplify one or more than 2 kinds among silicon dioxide, maltodextrine, glucose syrup, cellulose and others. Silicon dioxide and glucose syrup are preferably used in this invention. The ratio of silicon dioxide in the range of 1 to 10 %, glucose syrup (as dried) in the range of 5 to 25 % and dried extract of red vine leaves (as pure extract) in the range of 70 to 90 % in red vine leaves extract is preferable. The ratio of silicon dioxide 2-5 %, glucose syrup (as dried) 10-20 % and dried extract of red vine leaves (as pure extract) 75-85 % in red vine leaves extract is more preferable.

0018The 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-O-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 %. This total flavonoid (quercetin-3-O-beta-D-glucuronide) content in red vine leaves extract (for example, a case in which dried extract of red vine leaves (as pure extract) 80 %) is preferable from 0.5 to 20 %, more preferable from 1 to 10 %, special from 2 to 8 %.

0019To prevent and/or alleviate the discomfort of mild-to-moderate chronic venous insufficiency of the legs, the daily dosage of the aqueous extract of red vine leaves for an adult in equivalent quantity of dried extract of red vine leaves (pure extract) is usually from 64 to 800mg, preferably from 240 to 640 mg, more preferably from 280 to 600 mg and further more preferably 360 mg. The daily dosage of the aqueous extract of red vine leaves for an adult in equivalent quantity of red vine leaves extract is usually from 80 to 1000mg, preferably from 300 to 800 mg, more preferably 350 to 750 mg and further more preferably 450 mg.

0020The compositions according to this invention include diuretics as second active ingredients in addition to above aqueous extract of red vine leaves.

0021Diuretics used in this invention are not limited and determined if the agents contain diuretic action, however, for safety of this agent with minimum or no adverse event, diuretics with mild effects used in non-prescription drug and health food field for many years are preferable. In addition, types and dosage of diuretics change depending on whether this internal composition is pharmaceutical products or not. Examples of such diuretics are aminophylline, caffeine, herb and crude drug having diuretics action, and diuretically efficient minerals. Further in detail, caffeine group includes "caffeine and sodium benzoate", anhydrous caffeine, and caffeine etc.

0022In addition, examples of such crude drug and herb having diuretic action are poria sclerotium (<i>Poria</i>), akebia stem (<i>Akebiae caulis</i>), akebia fruit (<i>Akebiae fructus</i>), astragalus root (<i>Astragali radix</i>), alisma rhizome (<i>Alismatis rhizoma</i>), jujube (<i>Zizyphi fructus</i>), houttuynia herb (<i>Houttuyniae herba</i>), plantago seed (<i>Plantaginis semen</i>), plantago herb (<i>Plantaginis herba</i>), horsetail herb (<i>Equiseti herba</i>), gardenia fruit (<i>Gardeniae fructus</i>), nettle leaf (<i>Urticae folium</i>), nettle herb (<i>Urticae herba</i>), hibiscus rosell (<i>Hibiscus sabdariffa</i>), anemarrhena rhizome (<i>Anemarrhenae rhizoma</i>), motherwort herb (<i>Leonuri herba</i>), areca husk (<i>Arecae pericarpium</i>), abutilon seed (<i>Abutili semen</i>), campsis flower(<i>Campsitis flos</i>), bearberry leaf (<i>Uvae ursi folium</i>), atractylodes lancea rhizome (<i>Atractylodis Lanceae rhizoma</i>), Rice Bean (<i>Phaseoli semen</i>), nuphar rhizome (<i>Nupharis rhizoma</i>), elder (<i>Sambucus sieboldiana blume ex graebn</i>), inula root (<i>Inulae radix</i>), rose fruit (<i>Rosae fructus</i>), sinomenium stem (<i>Sinomeni caulis et rhizoma</i>), hedysarum (<i>Hedysarum polybotrys</i>), magnolia bark (<i>Magnoliae cortex</i>), job's-tears seed (<i>Coicis lacryma-jobii semen</i>), parslane herb (<i>Portulacae herba</i>), reed rhizome (<i>Phragmitis rhizoma</i>),polyporus (<i>Polyporus umbellatus fries</i>),inula flower (<i>Inulae flos</i>), pharbitis seed (<i>Pharbitidis semen</i>), pumice (<i>Pumex</i>), honeysuckle stem (<i>Lonicerae, caulis</i>),pepperweed seed (<i>Lepidii semen</i>), common scouring rush herb (<i>Equiseti herba</i>), physalis rhizome and root (<i>Physalitis rhizoma et radix</i>),kusnezoff monkshood root (<i>Aconiti kusnezoffii radix</i>), Chinese lobelia herb (<i>Lobeliae Chinensis herba</i>), beautiful sweetgum fruit (<i>Liquidambaris fructus</i>), aconite(prepared) (<i>Aconiti carmichaeli praeparata rad</i>), dwarf lilyturf tuber (<i>Ophiopogonis tuber</i>), twotoothed achyranthes root (<i>Achyranthis radix</i>), chinese waxgourd seed (<i>Benincasae semen</i>), white mulberry root-bark (<i>Mori cortex</i>), loquat leaf (<i>Eriobotryae folium</i>), pucture vine caltrop fruit (<i>Tribuli fructus</i>), natural water-content sodium sulfate (<i>Natrium sulfuricum</i>), elsholtzia herb (<i>Elsholtziae herba</i>), senega (<i>Senegae radix</i>), atractylodes rhizome (<i>Atractylodis rhizoma</i>), lilac pink herb (<i>Dianthi herba</i>), forsythia fruit <i>(Forsythiae fructus</i>), lalang grass rhizome <i>(Imperatae rhizoma</i>), prunellae spica <i>(Prunellae spica</i>), cubeb pepper <i>(Cubebae fructus</i>), corn silk <i>(Maydis stigmata</i>), lightyellow sophora root <i>(Sophorae radix</i>), albizzia bark <i>(Albizziae cortex</i>), belvedere fruit <i>(Kochiae fructus</i>), Chinese iris seed <i>(Iridis semen</i>), evodia fruit <i>(Evodiae fructus</i>), largeleaf gentian root <i>(Gentianae macrophyllae radix</i>), papermulberry fruit <i>(Broussonetiae fructus</i>), ramie root <i>(Boehmeriae radix</i>), rush <i>(Junci medulla</i>), photinia leaf <i>(Photiniae folium</i>), motherwort fruit <i>(Leonuri fructus</i>), dandelion <i>(Taraxaci herba</i>), sea-ear shell <i>(Haliotidis concha</i>), earthworm <i>(Lumbricus</i>), Japanese raisin tree seed <i>(Hoveniae semen</i>), pyrrosia herb <i>(Pyrrosiae herba</i>), vaccinium <i>(Vitis-idaea</i>), eupatorium herb <i>(Eupatorii herba</i>), cattall pollen <i>(Typhae pollen</i>), hydrangea <i>(Hydrangea macrophylla</i>), Hyssop <i>(Hyssopus</i><i>officinalis</i>), wild oat <i>(Avena sativa</i>), parsely <i>(Petroselinum crispum</i>), yarrow <i>(Achillea millefolium</i>), alfalfa <i>(Medicago sativa</i>), garden thyme <i>(Thymus vulgaris</i>), marsh mallow <i>(Althaea officinalis</i>), guarana <i>(Paullinia cupana</i>), cranberry <i>(Vaccinium oxycocos</i>), juniper <i>(Juniperus communis</i>), saw palmetto <i>(Serenoa repens</i>), dandelion <i>(Taraxacum officinale</i>), mate <i>(Ilex paraguayensis</i>), common mallow <i>(Malva sylvestris</i>), linden <i>(Tilia europaea</i>), rose hip <i>(Rosa canina</i>), valerian <i>(Valeriana officinalis</i>), angelica <i>(Angelica archangelica</i>), orange peel <i>(Citrus sinennsis</i>), citrus unshiu peel <i>(Aurantii nobilis pericarpium</i>), celery seed <i>(Apium graveolens</i>), Tarragon <i>(Artemisia dracunculus</i>), chicory <i>(Cichorium intybus</i>), dill seed <i>(Anethum graveolens</i>), parsley <i>(Pertroselinum crispm</i>), meadowsweet <i>(Filipendula ulmaria</i>), linden wood <i>(Tilia cordata</i>), linden flower<i>(Tilia platyphyllos</i>), linden <i>(Tilia europaea</i>), lemon <i>peel(Citrus llimon</i>), Gurmar <i>(Gymnema sylvestre</i>), fennel <i>(Foeniculum vulgare</i>), sweetleaf <i>(Stevia rebaudiana bertoni</i>), chicory <i>(Cichorium intybus</i>), hops <i>(Humulus lupulus</i>), mustard <i>(Sinapis alba</i>), achiote <i>(Bixa orellana</i>), yerba mate <i>(Ilex paraguayensis</i>), mutamba <i>(Guazoma ulmifolia lam.</i>), mullaca <i>(Physalis angulata</i>), perilla <i>(Perilla frutescens</i>), eucommia <i>(Eucommiae cortex</i>), Cha de Burge <i>(Cordia salicifolia</i>), Pearl barley <i>(Coicis fructus</i>), Goldenrod herb <i>(Solidago, Virgaureae herba</i>), Restharrow root <i>(Ononis spinosa radix</i>) and Java tea leaves : cats whiskers <i>(Orthosiphon aristatus</i>) etc. In addition, these crude drug and herb having diuretic action can be dried powder, extract, and fluidextract etc.

0023Minerals having diuretic efficacy are any sources of magnesium and potassium. Minerals used in this invention are preferably water soluble synthetic compounds such as chemical synthetic, enzyme synthetic and also natural products or natural products separated and purified. There is no limit for mineral form used in this invention. For example, the forms include mineral, salt, oxide, protein complex, complex of protein decomposed product, polysaccharide complex, complex of polysaccharide decomposed product, modified starch complex, cyclodextrin complex or metalloenzyme including minerals such as superoxide dismutase, glutathione peroxidase, acid phosphatase, metal activating enzyme including phosphoglucomutase, enzyme and coenzyme including metal except for active centers.

0024Exemplifying preferred examples of minerals for magnesium group include magnesium carbonate, magnesium sulfate, magnesium citrate, magnesium lactate, magnesium chloride, magnesium oxide, magnesium aluminum silicate, magnesium aluminometasilicate, magnesium hydroxide aluminum, magnesium L-aspartate and magnesium L-glutamate.

0025Magnesium stearate is water insoluble and thus cannot become a source of a mineral. Therefore, the term "diuretically effective mineral" does not include water insoluble magnesium salts such magnesium stearate.

0026Potassium group includes potassium chloride, potassium sulfate, potassium carbonate, potassium dihydrogen citrate, tripotassium citrate, potassium gluconate, potassium acetate, tripotassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, potassium hydroxide, aluminum potassium sulfate, potassium L-aspartate, and monopotassium L-glutamate.

0027Diuretics such as those aminophylline, caffeine, crude drug and herb having diuretic action and minerals etc. can be mixed with one or more than two kinds.

0028Combination amount of diuretics used in this invention components changes depend on types of diuretics and categorization as pharmaceutical products or foods, but a daily dose for an adult is between 1 to 18000 mg.

0029Specifically, daily combination amount of aminophylline is usually between 1 to 400 mg for an adult, preferably between 5 to 350 mg, more preferably between 10 to 300 mg. Daily combination amount of caffeine and anhydrous caffeine is usually between 2 to 900 mg for an adult, preferably between 5 to 700 mg, more preferably between 10 to 500 mg and daily combination amount of "caffeine and sodium benzoate" is usually between 2 to 1800 mg for an adult, preferably between 10 to 1200 mg, more preferably between 10 to 600 mg.

0030Daily combination amount of crude drug and herb having diuretic action is usually between 2 to 18000 mg as crude drug substance for an adult, preferably between 4 to 15000 mg, more preferably between 6 to 12000 mg. Combination amount of mineral is less than 700 mg as magnesium, preferably 1 to 600 mg, more preferably 3 to 500 mg. Potassium is between less than 4000 mg as potassium, preferably 1 to 3000 mg, more preferably 2 to 2000 mg.

0031The compositions according to this invention may be administered parentherally, preferably orally in divided doses, most preferably given once a day in the morning, especially before breakfast. Dose adjustment of the active ingredients may reflect age, body weight, and manifesting symptoms. In addition to active ingredients mentioned above, the internal compositions in this invention may also include other active ingredients.

0032The oral dosage form described in this invention can be used in various types of oral forms as tablets, granules, fine granules, powders, capsules, caplets, soft capsules, pills, oral solutions, syrups, dry syrups, chewable tablets, troches, effervescent tablets, drops, suspension, oral fast-dispersing tablets, etc. Any of these formulations may be prepared using regular methods, and, in addition to the aforementioned components, any excipients in common use may be used upon preparation of these formulations, if necessary. In addition, preparations formed into microparticles such as microcapsules, nanocapsules, microspheres, nanospheres, and included in the aforementioned formulations. For example, the active ingredients, i.e. an aqueous extract of red vine leaves and diuretics, can be various types of drug forms as separate granules, multi-layer granules, multi-layer tablets or dry coated tablets, tablets of separated granules, microcapsules, etc. Coating preparations such as sugarcoated tablets, film coating tablets, coating granule, can be used as well as chewable tablets, oral fast dispersing tablets, matrix tablets, matrix granules, effervescent tablets, dusting powder, solid solutions, etc. These methods can also be combined. Moreover, the properties of the inventive internal composition such as stability, release, continuance, disintegration, distinglation, dissolution, concealment of taste, improvement in usage etc. can be regulated by the addition of additives known in the art.

0033These oral dosage form described in this invention may be prepared using regular methods by adding generally available pharmaceutical additives and food additives such as excipients, binders, disintegrators, lubricants, coating agents, sugar coating agents, plasticizers, antifoaming agents, polish, foaming agents, antistatic agents, desiccant, surfactant, solubilizer, buffer agents, resolvents, solubilizing agents, solvents, diluents, stabilizers, emulsifying agents, suspension, suspending agents, dispersing agents, isotonizing agents, adsorbents, reducing agents, antioxidant, wetting agents, wet modifier, filler, extender, adhesives, viscous agent, softeners, pH modifiers, antiseptics, preservatives, sweetening agents, corrigent, refrigerative agents, flavoring agents, perfume, fragrance, and coloring matters to the active compounds. Examples of such additives are described in Japanese Pharmaceutical Excipients Directory 2000 (edited by Japan Pharmaceutical Excipients Council, issued by Yakuji Nippo, Ltd.) and The Japan's Specifications and Standards for Food Additives (issued by Japan Food Additives Association).

0034The compositions according to this invention can be provided as pharmaceutical products or foods. The compositions described in this invention are explained by the following practical examples. However, the scope of this invention is not limited to these practical examples.

Examples

Example 1

Capsules

0035The following ingredients were prepared as granules through regular methods, and capsule-filled to give an amount of 280 mg per one capsules. <tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Red vine leaves extract</entry><entry namest="col2" nameend="col2" align="left">450 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Alisma rhizome extract</entry><entry namest="col2" nameend="col2" align="left">50 g</entry></row><row><entry namest="col1" nameend="col1" align="left">(Alisma rhizome</entry><entry namest="col2" nameend="col2" align="left">500g)</entry></row><row><entry namest="col1" nameend="col1" align="left">Corn starch</entry><entry namest="col2" nameend="col2" align="left">30 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Light anhydrous silicic acid</entry><entry namest="col2" nameend="col2" align="left">6 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Talc</entry><entry namest="col2" nameend="col2" align="left">18 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Magnesium stearate</entry><entry namest="col2" nameend="col2" align="left">6 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col2" align="justify">(Red vine leaves extract = dried aqueous extract of red vine leaves (pure extract): silicon dioxide: glucose syrup (as dried glucose)) = 80: 3: 17 wt/wt%)</entry></row></tbody></tgroup></table></tables>

Example 2

Granules

0036The following ingredients were prepared as granules through a regular method to prepare mixed particles, and packed to give an amount of 2000 mg per one pack for granules. <tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Red vine leaves extract</entry><entry namest="col2" nameend="col2" align="left">225 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Poria sclerotium extract</entry><entry namest="col2" nameend="col2" align="left">8 g</entry></row><row><entry namest="col1" nameend="col1" align="left">(Poria sclerotium</entry><entry namest="col2" nameend="col2" align="left">240g)</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyporus extract</entry><entry namest="col2" nameend="col2" align="left">25 g</entry></row><row><entry namest="col1" nameend="col1" align="left">(Polyporus</entry><entry namest="col2" nameend="col2" align="left">250g)</entry></row><row><entry namest="col1" nameend="col1" align="left">Sinomenium stem extract</entry><entry namest="col2" nameend="col2" align="left">40 g</entry></row><row><entry namest="col1" nameend="col1" align="left">(Sinomenium stem</entry><entry namest="col2" nameend="col2" align="left">500g)</entry></row><row><entry namest="col1" nameend="col1" align="left">Aminophylline</entry><entry namest="col2" nameend="col2" align="left">10 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Calcium carboxymethylcellulose</entry><entry namest="col2" nameend="col2" align="left">80 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Mannitol</entry><entry namest="col2" nameend="col2" align="left">410 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Corn starch</entry><entry namest="col2" nameend="col2" align="left">182 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Tartaric acid</entry><entry namest="col2" nameend="col2" align="left">8 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Aspartame</entry><entry namest="col2" nameend="col2" align="left">8 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Acesulfame potassium</entry><entry namest="col2" nameend="col2" align="left">3 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Fragrant materials</entry><entry namest="col2" nameend="col2" align="left">1 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col2" align="justify">(Red vine leaves extract = dried aqueous extract of red vine leaves (pure extract): silicon dioxide: glucose syrup (as dried glucose)) = 80: 3: 17 wt/wt%)</entry></row></tbody></tgroup></table></tables>

Example 3

Powder

0037The following ingredients were homogeneously mixed. The resulted mixed particles were divided into portions of 1000 mg to prepare powder compositions. <tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Red vine leaves extract</entry><entry namest="col2" nameend="col2" align="left">450 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Akebia stem extract</entry><entry namest="col2" nameend="col2" align="left">100 g</entry></row><row><entry namest="col1" nameend="col1" align="left">(Akebia stem</entry><entry namest="col2" nameend="col2" align="left">2500g)</entry></row><row><entry namest="col1" nameend="col1" align="left">Astragalus root extract</entry><entry namest="col2" nameend="col2" align="left">50 g</entry></row><row><entry namest="col1" nameend="col1" align="left">(Astragalus root</entry><entry namest="col2" nameend="col2" align="left">500g)</entry></row><row><entry namest="col1" nameend="col1" align="left">Jujube extract</entry><entry namest="col2" nameend="col2" align="left">100 g</entry></row><row><entry namest="col1" nameend="col1" align="left">(Jujube</entry><entry namest="col2" nameend="col2" align="left">250g)</entry></row><row><entry namest="col1" nameend="col1" align="left">Pyridoxine hydrochloride</entry><entry namest="col2" nameend="col2" align="left">50 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Corn starch</entry><entry namest="col2" nameend="col2" align="left">124 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Lactose</entry><entry namest="col2" nameend="col2" align="left">108 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Light anhydrous silicic acid</entry><entry namest="col2" nameend="col2" align="left">10 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Magnesium stearate</entry><entry namest="col2" nameend="col2" align="left">8 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col2" align="justify">(Red vine leaves extract = dried aqueous extract of red vine leaves (pure extract): silicon dioxide: glucose syrup (as dried glucose)) = 80: 3: 17 wt/wt%)</entry></row></tbody></tgroup></table></tables>

Example 4

Tablet

0038The following ingredients were homogeneously mixed. The resulted mixed particles were compressed with a mold to prepare tablets at 300 mg each. <tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Red vine leaves extract</entry><entry namest="col2" nameend="col2" align="left">450 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Anhydrous caffeine</entry><entry namest="col2" nameend="col2" align="left">10 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Potassium L-aspartate</entry><entry namest="col2" nameend="col2" align="left">20 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Pyridoxine hydrochloride</entry><entry namest="col2" nameend="col2" align="left">10 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Lactose</entry><entry namest="col2" nameend="col2" align="left">100 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Microcrystalline cellulose</entry><entry namest="col2" nameend="col2" align="left">296 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Light anhydrous silicic acid</entry><entry namest="col2" nameend="col2" align="left">7 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Magnesium stearate</entry><entry namest="col2" nameend="col2" align="left">5 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Talc</entry><entry namest="col2" nameend="col2" align="left">2 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col2" align="justify">(Red vine leaves extract = dried aqueous extract of red vine leaves (pure extract): silicon dioxide: glucose syrup (as dried glucose)) = 80: 3: 17 wt/wt%)</entry></row></tbody></tgroup></table></tables>