US 20060189512A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0189512 A1 Ehrenkranz (43) Pub. Date: Aug. 24, 2006

(54) COMPOSITIONS CONTAINING BOTANICAL Related US. Application Data EXTRACTS RICH IN PHLORIZIN AND METHODS FOR USING SUCH (60) Provisional application No. 60/645,796, ?led on Jan. COMPOSITIONS IN BLOOD GLUCOSE 21, 2005 MODIFICATION AND TO AFFECT AGING _ _ _ _ Publication Classi?cation

(51) Int. Cl. (76) Inventor: Joel R. L. Ehrenkranz, Salt Lake City, A 61K 38/28 (200601) UT (Us) A61K 31/7048 (2006.01) (52) US. Cl...... 514/3; 514/27 Correspondence Address: MORRISS O’BRYANT COMPAGNI, RC. (57) ABSTRACT 136 SOUTH MAIN STREET SUITE 700 Compositions are disclosed Which contain therapeutically SALT LAKE CITY, UT 84101 (US) e?‘ective amounts of phloriZin extract for effecting modi? cation of blood glucose and insulin, for facilitating Weight loss, preventing Weight gain and for providing bene?cial (21) Appl, NQ; 11/336,629 effects in the aging process. Methods of treating animals With phloriZin extract compositions to treat the aforemen (22) Filed: Jan. 20, 2006 tioned conditions of the body are also disclosed. US 2006/0189512 A1 Aug. 24, 2006

COMPOSITIONS CONTAINING BOTANICAL [0009] The administration of phloriZin extracts is demon EXTRACTS RICH IN PHLORIZIN AND METHODS strated to be effective in reducing or bene?cially modifying FOR USING SUCH COMPOSITIONS IN BLOOD blood glucose and insulin levels, to effect Weight loss or GLUCOSE MODIFICATION AND TO AFFECT prevent Weight gain, and to have bene?cial effects on the AGING aging process and to increase longevity.

CROSS REFERENCE TO RELATED [0010] The phloriZin extracts may be derived from any APPLICATIONS source, particularly including but not limited to apple and cherry trees, apple fruit, pommice, peels, cider, and straW [0001] This is a non-provisional application claiming pri berry plants. The extracts may, in particular, be obtained ority to US. provisional application Ser. No. 60/645,796 from the tWigs, bark, immature or mature fruits, or other ?led Jan. 21, 2005. aerial and subsurface parts of the tree or from fruit-bearing plants such as straWberry plants. BACKGROUND [0011] The phloriZin extracts used in accordance With the [0002] 1. Field of the Invention present invention comprise a standardized phloriZin content [0003] This invention relates to the modi?cation of blood of from betWeen 0.5% to 99%. A particularly suitable glucose and insulin levels in the treatment of certain diseases phloriZin extract of the present invention contains a stan or medical conditions of the body, as Well as the control of dardiZed phloriZin content of about 20% to about 80%, and Weight, aging and development of diseases. This invention about 40% may be suitable for most administrations. The speci?cally relates to the use and administration of botanical phloriZin extracts of the present invention may also contain compositions rich in phloriZin in the modi?cation of blood other polyphenols including, for example, phloretin, cat glucose and insulin, to facilitate Weight loss and to provide echins, chlorogenic acid, quercetin and polymers thereof. bene?cial effects in the aging process. [0012] The phloriZin extracts of the present invention have [0004] 2. Statement of Related Art been demonstrated to have bene?cial effects in producing glucosuria, decreasing postprandial rises in glucose and [0005] PhloriZin, a dihydrochalcone, is a naturally-occur insulin levels, elimination of reactive hypoglycemia, control ring product and dietary constituent found in a variety of of stress hyperglycemia, Weight loss and in preventing fruit trees such as apple, and in fruit-bearing plants such as Weight gain. Additionally, data shoW that there is a dose strawberry. PhloriZin has been shoWn to be present in the response relationship betWeen the amount of phloriZin root, bark, shoots, leaves and fruit of certain fruit trees, and extract ingested and the amount of glucose excreted. Con is also present in the plant parts and fruit of, for example, sequently, the more phloriZin extract one takes, the more straWberry plants. glucose, calories, and Weight one loses. The administration [0006] PhloriZin has been used in the past as a pharma of phloriZin is also shoWn to have potentially bene?cial ceutical tool for the evaluation of renal function and as a tool anti-aging effects and to mimic mechanisms knoWn to for investigation of glucose transport, as disclosed in US. increase and activate increased longevity in animals. Pat. No. 6,448,232. PhloriZin has also been demonstrated to be effective in improving insulin sensitivity by loWering DETAILED DESCRIPTION OF THE blood sugar and has been suggested as useful in other blood INVENTION glucose modulating methodologies. [0013] The phloriZin extracts of the present invention may be derived from any source of phloriZin, including but not BRIEF DESCRIPTION OF THE INVENTION limited to fruit trees, the fruit of such trees and fruit-bearing [0007] In accordance With the present invention, methods plants, including the fruit of such plants. In particular, for treating disease conditions, facilitating Weight loss, pre hoWever, phloriZin extracts of the present invention may, venting the development of disease or other undesirable most suitably, be derived from apple trees and strawberry conditions of the body and affecting aging in animals is plants. The phloriZin extract may be derived from tWigs, mediated by modifying blood glucose and insulin levels bark, immature or mature fruits, or other aerial parts of the through the use or administration of phloriZin extracts to tree, from pommice, peels and cider, and from subsurface animals. As used herein, “animals” or “patients” is intended parts (e. g., roots) of the tree. PhloriZin may also be extracted to include both human and non-human animals. PhloriZin from all parts of straWberry plants, including the fruit. The extracts are administered in amounts that effectively reduce phloriZin extracts of the present invention may also contain glucose and insulin levels in the blood, and in effective other polyphenols including, for example, phloretin, cat amounts to control Weight loss or prevent Weight gain. echins, chlorogenic acid, quercetin and polymers thereof. Such polyphenols may be extracted from the same source as [0008] The phloriZin extract effectively modi?es blood the phloriZin. glucose and insulin levels, in accordance With the invention, by being administered in an effective or therapeutic amount [0014] The phloriZin extracts of the present invention may or dosage, prior to the intake of food or a meal. By “effective be produced by any means or method that produces the amount”, “therapeutic amount” or “effective dose” is meant desired concentration of phloriZin. Exemplar methods of that amount of phloriZin extract su?icient to elicit the desired producing phloriZin extracts include Water-based extraction pharmacological or therapeutic effects, thus resulting in of target materials by soaking parts of the tree (e.g., apple effective treatment, or prevention, of a disorder, disease or tree), such as tWigs, bark and the fruit of the tree in Water. body condition. The phloriZin extract is administered Within Extraction may also be effected by use of ethanol or other about 30 minutes to about 60 minutes prior to consumption suitable materials, as Well as by supercritical CO 2 extrac of food or a meal. tion. Such extraction methods are Well-knoWn in the art. US 2006/0189512 A1 Aug. 24, 2006

[0015] The phloriZin extracts may be administered in any —60, 0, 30 and 60 minutes relative to the consumption of desired form including orally, parenterally, by injection or food. It can be seen from the test results that glucosuria by suppositories by knoWn methods that are standard in the increases and blood glucose decreases With higher dosages art. A preferred formulation for administration is as a dietary of phloriZin. supplement or nutraceutical that is in tablet, capsule or poWder form for oral administration. However, pharmaceu TABLE 1 tical compositions (Wt. %) containing phloriZin extract as the active ingredient, along With a suitable carrier or vehicle, blood is Within the scope of the invention. The means for forming Dose Time glucose Blood glu diff Urine glucose such administrable forms are Well-known in the art. The (gram) (min) (mgdl) (mg/d1) (mgdl) phloriZin extracts used in accordance With the present inven tion comprise a standardized phloriZin content of from 0 —60 107 0 0 betWeen 0.5% to 99%. A particularly suitable phloriZin 0 0 100 —7 0 extract of the present invention contains a standardized 0 30 165 58 0 phloriZin content of about 20% to about 80%, With a 0 60 120 13 0 preferred content of about 40%. 0 90 0 1 —60 96 0 0 [0016] The phloriZin extracts may, in certain forms, dem 1 0 111 15 100 onstrate limited or compromised bioavailability. Thus, phlo 1 30 152 56 250 riZin extracts of the present invention may be provided in 1 60 113 17 250 encapsulated forms, such as complexing phloriZin With 1 90 0 phosphotidylcholine, or delivering phloriZin in a solution/ 1.5 —60 95 0 0 suspension With organic solvents such as polypropylene 1.5 0 103 8 250 glycol, to increase bioavailability and extend the duration of 1.5 30 137 42 500 the effectiveness of the product. Other methods of increasing 1.5 60 141 46 500 bioavailability of the phlorZin extracts may be employed as 1.5 90 0 required. 2 —60 110 0 0 2 0 110 0 250 [0017] The administered dose of phrloriZin extract in 2 30 140 30 500 accordance With the present invention may be from about 3 2 60 138 28 500 grams to about 30 grams per day. The daily dosage is 2 90 0 administered in three separate doses comprising betWeen 2.5 —60 105 0 0 about one gram to about 10 grams of phloriZin taken prior 2.5 0 95 —10 1000 to the consumption of food or a meal. Each preprandial 2.5 30 133 28 1000 dosage may be taken from betWeen about 30 minutes to an 2.5 60 118 13 500 hour before consumption of a meal. The effective results of 2.5 90 85 —20 250 the intake of phloriZin extract are described more fully 2.5 120 90 —15 0 beloW. [0018] The data in Table 1, immediately beloW, generally demonstrate that glucosuria increases and blood glucose [0019] Graph A, immediately beloW, further demonstrates levels decrease folloWing consumption of a meal When the relative effects of an administration of varying dosages, phloriZin is administered prior to the meal on an empty from 0.0 grams to 2.5 grams, of a phloriZin extract stan stomach. Adult male subjects Were provided either a placebo capsule or a capsule containing about 40% phloriZin extract dardiZed to about a 40% content on blood glucose levels in an amount of either 1 gm, 1.5 g, 2.0 g or 2.5 g. The folloWing consumption of 52 grams of carbohydrate sixty capsules Were taken orally sixty minutes prior to taking a minutes after oral ingestion of the phloriZin. It can be seen meal. The subjects Were fed a meal of 52 grams of sugar at that blood glucose levels are appreciably loWered With an time 0. Blood and urine glucose levels Were measured at increased dosage of phloriZin. US 2006/0189512 A1 Aug. 24, 2006

Blood glucose levels following ingesting of apple extract formula at -60 minutes and 52 grams CHO at time 0

190

170- ’ ~~ a

150

—-0— Dose 1 gram 130 7' + Dose 1.5 grams Bloodglucose(mgldl) Dose 2 grams ~><— Dose 2.5 grams + Dose 0 gram

so

50 r v -30 0 3O 60 90 Time (min) US 2006/0189512 A1 Aug. 24, 2006

[0020] The data of TABLE 11, immediately below, further demonstrate the modi?cation of blood glucose levels TABLE ll-continued affected by administration of 1.5 grams of 40% phloriZin extract administered sixty minutes prior to the consumption Blood Blood glucose of a 100 gram carbohydrate meal (600 Kcal). Capsules Time (min) glucose (mg/d1) change (% from baseline)

TABLE 11 Phlorizin —60 97 0.00% Ate lunch 0 79 —18.00% Blood Blood glucose 30 1 13 1 6.00% Capsules Time (min) glucose (mg/d1) change (% from baseline) 60 1 18 21.00% 90 123 26.00% Placebo —60 111 0.00% Ate lunch 0 107 —4.00% 120 99 2.00% 30 134 23.00% 60 142 31.00% 90 117 6.00% 120 130 19.00% [0021] B, immediately beloW, further demonstrates these changes. US 2006/0189512 A1 Aug. 24, 2006

Blood glucose levels as a function of time for TN 1.5 9 Apple SEtaken 1 hr before lunch - Lunch (600 Kcal - 100 9 CH0) was eaten at time 0

7140

130

= i- v 420'» k E m g’ 1 O 3 1 U —Q—Placebo o g —I— Phlorizin 7,, -- -- 400 ‘U 0 2 m 90 _ e m A l 4» e

---- -'e0

70- i i i * ~ ir-~~—-____-—

5O . ‘ T ‘ -1OO ~50 O 50 100 150 Time (min) US 2006/0189512 A1 Aug. 24, 2006

[0022] Table III, immediately following, displays the 1.5 grams of 40% phloriZin extract 30 minutes before taking effects of phloriZin on the postprandial rise in glucose and a meal. The subjects had not eaten for at least 4 hours prior insulin levels. The subjects Were nine healthy adult normal to consuming the meal so that the phloriZin Was adminis volunteers. Each subject served as his or her oWn control. tered on an empty stomach. Subjects took a placebo pill one hour prior to carbohydrate [0024] The subjects Were Weighed periodically over a ingestion on one day and 1.5 grams of phloriZin on another. period of from seven to thirty-three days. The subjects Who Were Weighed at seven days had an average Weight loss of The phloriZin extract content Was standardized to about 8 lbs. Weight loss for all of the subjects increased over the 40%. Glucose and insulin levels Were measured at frequent subsequent 19 days. The data from this study is shoWn in intervals. The data in this table shoW that phloriZin, com Table IV beloW.

TABLE IV

TN WG LM YT AE IE GW VV GG CF

210 252 210 307 242 202 145 185 180 161 241 160 297 159 198 240 290 236.5 159 198 287 196.6 140 177 235 285.5 158 233.5 195 231 157 237 205 193.8 175 155

284 153 pared to placebo, produced a statistically signi?cant blunting [0025] The bene?cial effect of the phloriZin extracts of the of the rise in serum glucose and insulin levels folloWing present invention on modi?cation of glucose transport, carbohydrate ingestion. blood and urine glucose levels, blood insulin levels, and Weight loss are enhanced by the synergistic effects of other TABLE III elements administered With phloriZin extract of the present invention. Such synergistic effects are potentially mediated Phlorizin Placebo by quercetin, phloretin, epicatechin, catechins, chlorogenic 60 min. — baseline 60 min. — baseline p acid, their polymers and other elements extracted from fruit Glucose (mg/d1) trees or plants. N 9 9 0.016 [0026] Additionally, there is a demonstrated synergistic Mean 3 1. 11 5 0.78 Standard deviation 26.41 28.77 effect on the modi?cation of glucose transport, blood and Median 26.0 52.0 urine glucose levels, blood insulin levels and Weight loss in Range (1482) (1290) individuals With type 1 or type 2 diabetes When the phloriZin Insulin (mIU/ml) extract of the present invention is administered With diabe N 9 9 0.045 tes-related pharmaceuticals including, but not limited to, Mean 29.50 34.25 Standard deviation 17.29 35.33 insulin, insulin secretogogues, insulin sensitiZers (both thia Median 23.0 39.0 Zolidinediones and metformin), alpha-glucosidase inhibi Range (14467) (134118) tors, or With other plant-based extracts With hypoglycemic properties, or both plant-based extracts and diabetes related [0023] The administration of phloriZin from an apple pharmaceuticals. The folloWing Examples are illustrative of extract has further been shoWn to have bene?cial effects in these effects. Weight loss. As an example, a study group Was treated With phloriZin for a period of fourteen to thirty-three days to EXAMPLE I determine the effect of the extract on Weight loss. The study [0027] A thirty-one year old female With a ?fteen year group consisted of ten adults, comprising both males and history of type 2 diabetes mellitus, Who Was not taking any females, aged 24 to 71. The initial Weights of the subjects anti-diabetic medications, Was administered from betWeen 1 ranged from betWeen 145 and 307 pounds. The subjects and 5 grams of phloriZin extract, standardiZed to a content Were told not to change their routine eating or exercise habits of about 40%, thirty minutes before taking a meal. The test for the period of the study. The subjects Were administered results Were as folloWs: US 2006/0189512 A1 Aug. 24, 2006

lechequilla, Agave salmiana, Ageratina petiolaris, Agera tum conyzoides, Agrimonia eupatpria, Ajuga iva, Albizzia odoratissima seed, Alliona choisyi, Allium cepa, Allium After taking 3 Three months grams of apple after sativum, Alloispermum integrifolium, Aloe barbadensis, extract three discontinuing Aloe vera, Alpinia o?icinarum, Ambrosia artemisiifolia, Prior to starting times a day apple American ginseng leaf, Ammi visnaga, Amor seco, Anacar apple extract before meals extract dium occidentale, Anamu, Ananas comosus, Andiroba, Fasting glucose 160 mgdl 146 155 Andrographis paniculata, Anethum graveolens, Annona Fasting insulin 43 microIU/ml 44 64 cherimola, Annona glabra, Annona muricata, Anoectochilus Hemoglobin A1C 8.1% 7.3 7.6 Weight 276 lbs 266 268 formosanus, Apium graveolens, Aplidium conicum, Apodan thera buraeavi, Aporocactus ?agelliformis, Arachis hypogaea, Arceuthobium vaginatum, Arctostaphylos pun gens, Argemone mexicana, Argemone ochroleuca, Arge EXAMPLE H mone platyceras, Argyria cuneater, Argyria speciosa, Aris [0028] A 71 year old male with a seventeen year history of tolochia asclepiadifolia, Aristolochia malacophylla, diabetes mellitus, who was taking prescribed insulin for the Aristolochia sericea, Artemisia absinthium, Artemisia herba condition, was administered from between 1 and 5 grams of alba, Artemisia ludoviciana, Artemisia pallens wall, Arte phloriZin extract, standardized to a content of 40%, thirty misia santonicum, Artemisia vulgaris, Asclepias linaria, minutes before taking a meal. The test results were as Asparagus racemosus, Asteracantha longifolia, Astragalus follows: membranaceus, Atriplex halimus, Avena saliva, Averrhoa bilimbi, Azadirachta indica leaf, Baikal skullcap, Balanites aegyptiaca fruits, Bambusa dendrocalamus, Banaba, Barosma betulina, Bauhinia candicans, Bauhinia divari After taking 3 gm cata, Bauhinia for?cata leaves, Bauhinia retusa seed, Ba Prior to of apple extract Three months after starting three times a day discontinuing apple wei-die-huang-wan, Begonia heracleifolia, Berberine, Ber apple extract before meals extract beris moranensis, Bergenia ligulata, Beta vulgaris, Bidens aurea, Bidens leucantha, Bidens odorata, Bidens pilosa, Fasting glucose 342 327 395 Bignonia tuira, Black pepper, Bocconia arborea, Bombyx Fasting insulin n/a n/a n/a Hemoglobin A1C 10.8 10.2 12.2 mori, Bouvardia ternifolia, Brassica nigra, Brassica olera weight 244 234 238 cea var. gongylodes, Brazilian peppertree, Brickellia cavanillesii, Brickellia squarrosa, Brickellia veronicaefolia, Bridelia ferruginea, Brosium alicastrum, Bryonia alba, Buchnera pusilla, Buckwheat, Buddleia stachyoides, EXAMPLE III Buddleja Americana, Buddleja cordata, Buphorbia pros [0029] A 69 year old male with a ?ve year history of type trate, Bursera simaruba, Byrsonima crassifolia, Cacalia 2 diabetes, and who was on a prescribed regimen of met decompisita, Cacalia peltata, Caesalpinia bonducella, formin for the condition, was administered from between 1 Cajueiro, Calamintha macrostema, Calamintha o?icinalis and 5 grams of phloriZin extract, standardized to a content moench, Calea hypoleuca, Calea integrifolia, Calea Zacat of 40%, thirty minutes before taking a meal. The test results echichi, Calliandra anomala, Callicarpa acuminate, Camel were as follows: lia sinensis, Cana?stula, Capparis deciduas, Capraria bi?'ora, Capsicum annum, Caralluma attenuate, Caralluma edulis, Carica papaya, Carqueja, Carya, Carya illinoensis, Casearia esculenta, Casimiroa edulis, Cassia alata leaf After taking 3 gm extract, Cassia ?stula, Cassia skinneri, Cassia tomentosa, Prior to of apple extract One month after starting three times a day discontinuing apple Castela texana, Castela tortuosa, Castilleja mutis, Cat apple extract before meals extract echin-gallate, Catharanthus roseus, Catuaba, Cecropia obtusifolia, Cecropia peltata, Ceiba pentandra, Celosia Fasting glucose 138 140 143 argentea linn, Centaurea aspera, Centaurium brachycalyx, Fasting insulin n/a n/a n/a Hemoglobin A1C 6.5 6.3 n/a Centaurium calycosum, Centella asiatica, Chamaecrista weight 246.5 236.5 246.5 hispidula, Chamaemelum nobile, Chanca piedra, Chenopo dium glaucum, Chitosan, Choline esterase, Chromolaena bigelovii, Cinnamomum cassia, Cinnamomum verum, Cin [0030] Examples of plant-based substances and/or extracts namon, Cinnamon bark, Cirsium mexacanum, Cirsium pas having hypoglycemic properties, and which provide syner cuarense, Cirsium rhaphilepis, Cissampelos pareira, Cissus gistic effect in combination with the phloriZin extract of the sicyoides, Citrullus colocynthis, Citrus aurantifolia, Citrus present invention to bene?cially modify glucose transport, limetta, Citrus sinensis, Clausena anisata (wiild) hook, blood and urine glucose levels, blood insulin levels and Clavillia, Cleome droserifolia, Cnidoscolus aconitifolius, weight loss include the following: Abroma augusta, Cnidoscolus chayamansa, Cnidoscolus multilobus, Coc Abutilon lignosum, Abutilon trisulcatum, Acacia Arabica, cinia cordifolia, Coccinia indica, Co?dea Arabica, Acacia catechu seed, Acacia melanoxylon, Acacia retinodes, Cogniauxia podoleana baillon, Coix lacryma-jobi, Combre Acacia suma seed, Achyranthes aspera, Acosmium pana tum farinosum, Commelina communis, Convolvuls mycro mense bark, Acourtia thurberi, Acrocomia mexicana, Aegle phyllus, Convolvulus pluricaulis, Conyza ?laginoides, marmelos, Agaricus bisporus, Agaricus blazei, Agarista Conyza gnaphalioides, Cordia elaeagnoides, Cordia tinifo mexicana, Agastache mexicana, Agave atrovirens, Agave lia, Coriandrum sativum L., Cornifructus, Coronopus didy US 2006/0189512 A1 Aug. 24, 2006

mus, Costus mexicanus, Costus rubber, Costus spicatus, L., Nopalea cochenillifera, Nopalea inaperta, Ocimum basi Crataegus mexicana, Crataegus pubescens, Crinum, Crota licum, ocimum ?avonoids orientin, Ocimum gratissimum, laria acapulcensis, Croton draco, Croton torreyanus, Cryp Ocimum sanctum leaf, Oldenlandia a?inis, Olea europaea, tostegia grandi?ora, Cucurbita?cifolia, Cucurbita maxima, Oleum origami, Olive leaf, Onosma echioides, Opuntia Cucurbita mexicana, Cuminum nigrum, Curcuma longa, atropes, Opuntia?cus-indica (L.), Opuntiafulgida, Opuntia Cuscuta jalapensis, Cyamopis tetragonoloba (Linn.), guilanchi, Opuntia imbricate, Opuntia lindheimeri englem, Cyathea fulva, Cyclocarya paliurus, Cynanchum atratum, Opuntia megacantha, Opuntia streptacantha, Origanum Cynara scolymus, Cynodon dactylon, Daidzin, Datura metel majorana leaves, Origanum vulgare, Orthosiphon sta (Linn.), Dauvus carota, Di huang, Diasulin, Die-huang mineus, Pachira aquatica, Pachycereus, Pachycereus prin wan, Dioscorea dumetorum, Diospyros digyna, Dorstenia glei, Packera candidissima, Paeonia lacti?ora, Panax gin contrajerva, Duranta repens, Dyssodia micropoides, seng, Panax quinquelfolius, Pandanus odorus, Parathesis lenticellata, Parkinsonia aculeate, Parmentiera aculeate, Echinacea purpurea, Elaphoglossum, Elettaria cardamo Parthenium hysterophorus, Pau d ’arco, Pavonia mum, Eleutherococcus senticosus, Embauba, Emblica o?i schiedeana, Pedra hume caa, Pelvetia babingtonnii de toni, cinalis, Enicostemma littorale, Equisetum giganteum, Equi Persea Americana, Petroselinum crispum, Phaseolus vul setum hyemale, Equisetum myriochaetum, Eriobotrya garis, Phlebodium aureum, Phoradendron tomentosum, japonica, Erva tostao, Espinheira santa, Eucalyptus glob Phragmites australis, Phyllanthus sellowianus, Physalis ules, Eugeniajambolana, Eupatorium, Euphorbia maculate, coztomatl, Physalis philadelphica, Phytosterin, Picao preto, Euphorbia prostrate, Euphrasia o?icinalis, Eysenhardtia Picrorrhiza kurroa, Pimenta o?icinalis, Pimpinella anisum, polystachya, F religiosa L., Fangchinoline, Fedegoso, Ficus Piper auritum, Piper hispidum, Piper nigrum, Piper sanc bengalensis, ?cus glomerata, Ficus racemosa bark extract, tum, Piper schideanum, Pithecellobium dulce, Planta aus Ficus verens, Foeniculum vulgare, Folium mori, Fouquieria tralis, Plantago major L., Plumbago scandens, Plumeria splendens, Fraxinus alba, Fraxinus excelsior, French lilac, rubra, Polygonati o?icinalis rhizome, Polygonati rhizome, Fumaria parvi?ora, Galega o?icinalis, Ganoderma luci Polygonatum sibricum, Polygonum acre, Pomegranate dum, Genistein, Gentiana olivieri, Gervao, Ginseng, Globu ?ower, Populus alba, Portulaca oleracae, Potentillafulgens laria alypum, Glycine max, Gongronema latifolium leaves, L., Poterium spinosum, Prunus dulcis, Psacalium decom Gossypium birsutum, Graviola, Green tea polyphenols, positum, Psacalium peltatum, Psychotria oleoides, Ptero Grewia asiatica, Guacatonga, Guaiacum coulteri, Guai carpus marsupium wood, Pterocarpus santalinus L., Pue acum sanctum, Guar gum, Guarana, Guardiola angustifo mus boldus, Pueraria thunbergiana, Puerarin, Punica lia, Guardiola tulocarpus, Guava, Guazuma ulmifolia, Gym granatum Linn., Quassia amara, Quercetin, Ramulus mori, nema hirsute, Gymnema montanum, Gymnema sylvestre, Red wine polyphenols, Rehmannia glutinosa. Retama Gymnema yunnanense extract, Gynostemma pentaphyllum, raetam, Rhazya stricta, Rhizomes of alpinia o?inarum Gynura procumbens, Haemahtoxylon brasiletto, Hamamelis hance, Rhizomes ofpolygala senega, Rhodiola rosea, Rhus virginiana, Hamelia patens, Hamiltonia suaveolens, Haplo vernici?ua, Rhynchelytrum repens (Willd), Rosmarinus o?i pappus venetus, Harpagophytum procumbens, Hawthorn, cinalis, Rubusfructicosus, Saccharomyces cerevisiae, Sala Hechtia melanocarpa, Heterotheca inuloides, Hibiscus cia oblonga wall, Salacia reticulate, Salvia o?icinalis, rosa-sinensis L., Hidalgoa ternate, Hintonia lati?ora, Samambaia, Sangre de grado, Sanguis draxonis, Sclero Hippocratea excelsa, Holy basil leaves, Hypoxis hemero carya birrea, Scoparia dulcis, Scutellaria baicalensis, callidea corm, Ibervillea sonorae, lpomoea aquatica, lpo Securigera securidaca L. seed, Semecarpus anacardium moea batatas L., Ipomoea pescaprae, Ipomoea starts, Linn., Sida cordifolia, Silybum marianum, Simarouba, Smal Iporuru, Jambolan, Jatoba, Jatropha dioica, Jatropha lantus sonchifolius, Spathodea campanulata stem bark, elbae, Juliania adstringens, Jurubeba, Justicia spicigera, Spergularia purpurea, Stephania tetrandra radix, Stevia Kalanchoepinnata, Kalopanax pictus extract, Karwinskia rebaudiana, Steviol, Suma, Swertia chirayita, Syzigium ara humboldtiana, Kohleria, Konjac-mannan, Lagerstroemia maticum, Syzigium cumini seeds, Syzygium alternifolium speciosa, Larrea tridentate, Latium, Laurus nobilis, Lenti (Wt) walp, Syzygium cumini, Tamarindus indica, Taraxacum nus edodes. Lepechinia caulescens, Lepidium sativum, Lepi o?icinale, Tayuya, Telfaria occidentalis, Terminalia arjuna, dium virginicum, Leucaena leucocephala (Lam.) de wit, Terminalia catappa Linn., Terminalia chebula, Terminalia Leucas lavandulaefolia, Leucophyllumtexanum, Ligusticum pallida fruit, Tetrapleura tetraptera, Teucrium polium, porteria, Ligustrum japonicum, Linum usitatissimum, Thunbergia laurifolia Linn., linospora cordifolia, lino Lodiocea sechellarum, Loeselia coccinea, Loeselia mexi spora crispa, Trifolium alexandrinum, Trigonella foenum cana, Lonchocarpus cruentus, Lopezia racemosa, Lopho graecum, Triterpenoid glycosides, Triticum repens, Tulasi, cereus schoftii, Lupinus termis, Lycium barbarum, Lyophyl Turnera aphrodisiaca, Turnera dijjrusa, Uncaria, Uncaria lum decastes, Lysiloma acapulcense, Lythrum salicaria, tomentosa, Uraria Picta, Urtica dioica, Vanilla planifolia, Macela, Malmae depresa, Malvastrum coromandelianum, Verbesina encelioides, Vernonia colorata leaves, l/icenin. Manaca, Mangifera indica, Marche, Marrubium vulgare, l/igna angularis, Withania coagulans dunal, Withania som Medicago sativa. Medicago sativa, Melothria pendula, nifera, Yerba mate, Zanthoxylum armatum, Zingiber o?ici Memecylon umbellatum, Mentha piperita, Mentha rotundi nale, Zizyphus sativa, Zizyphus spina-christi, and Zygophyl folia, Mentha suaveolens, Mimosa zygophylla, Mirabilis lum gaetulum. jalapa, Mitragyna inermis (Wild), Momordica charantia, Momordica cymbalaria hook, Morinda lucida leave, Morus [0031] Caloric restriction has repeatedly been shown to alba, Morus indica, Morus nigra, Mucuna pruriens, Muira sloW the aging process and to increase the life span of a puama, Mullaca, Mulungu, Musa paradisiacal, Musa sapi spectrum of organisms ranging from yeast to primates. The entum, Mutamba, Myrcia uni?ora, Myricetin, Myristica mechanisms through Which caloric restriction act have not fragrans, Nasturtium o?icinale, Nelumbo nucifera rhizome, been clearly delineated; hoWeVer reduced levels of glucose Nepeta cataria, Nescafe, Neurolaena lobata, Nigella sativa and insulin are hallmarks of caloric restriction in both US 2006/0189512 A1 Aug. 24, 2006

rodents and primates. PhloriZin has been shown to decrease loss and in prevention of Weight gain, and has bene?cial glucose and insulin levels in a manner analogous to caloric effects in increasing longevity and producing anti-aging restriction, hence the administration of phloriZin extract of affects in animals. The foregoing description of the speci?c the present invention represents a caloric restriction embodiments Will so fully reveal the general nature of the mimetic. invention that others can, by applying current knowledge, readily modify and/or adapt for various applications such [0032] By decreasing glucose levels, phloriZin extract is speci?c embodiments Without departing from the generic able to decrease the formation of advanced glycosylation concept and therefore such adaptations are intended to be end products. Hemoglobin A1 c, routinely used in the assess comprehended Within the meaning and range of equivalents ment of diabetes control, is an example of an advanced of the disclosed embodiments. It is to be understood that the glycosylation end product. The data presented above in phraseology or terminology employed herein is for the Examples 1, H and Ill demonstrate that the phloriZin extract purpose of description only and not of limitation. of the present invention decreases advanced glycosylation end product formation and concentration. Decreasing the What is claimed is: amounts of advanced glycosylation end products is associ 1. A composition for bene?cially modifying blood and ated With decreased aging-related pathologies, such as dia urine glucose levels and facilitating Weight loss, comprising betes mellitus, AlZheimers disease, atherosclerosis, renal a therapeutic amount of from betWeen about 0.5% to about disease, osteoarthritis, and osteoporosis. Thus, by loWering 99% phloriZin extract. glucose levels, phloriZin extract blunts the development of 2. The composition of claim 1 Wherein said phloriZin age-related pathologies due to the formation of advanced extract concentration is about 20 to about 80%. glycosylation end products. 3. The composition of claim 2 Wherein said phloriZin [0033] Another mechanism through Which phloriZin extract concentration is about 40%. extract retards the aging process is via the genetic control of 4. The composition of claim 1 Wherein said phloriZin DNA transcription. Studies in yeast, Worms, fruit ?ies, and extract is derived from the fruit, tWigs, bark and aerial parts rodents implicate a family of genes, termed sirtuins, Which of fruit trees, from the fruit and plant parts of straWberry act as histone deacetylase enZymes, to regulate DNA tran plants, and combinations thereof. scription. A number of observations demonstrate the critical 5. The composition of claim 1 Wherein said phloriZin role sirtuins play in the regulation of aging. For example, in extract is complexed to increase bioavailability. yeast and fruit?ies, caloric restriction increases sirtuin activ 6. The composition of claim 1 further comprising a ity, and duplicating the sirtuin 2 gene increases lifespan in plant-based substance having hypoglycemic properties. these species, While deleting the sirtuin 2 gene reverses the 7. The composition of claim 1 further comprising a longevity effect of caloric restriction. pharmaceutical substance selected from the group compris ing insulin, insulin sensitiZers, insulin secretagogues and [0034] A cell-based ?uorescence deacetylase assay, SlRTl alpha-glucosidase inhibitors. Fluorimetric Drug Discovery Kit, obtained from BIOMOL 8. A dietary supplement for modifying blood and urine Research Laboratories, Inc., Plymouth Meeting, Pa. Was glucose levels, loWering postprandial insulin levels, facili used to measure the effects of various polyphenols in apple tating Weight loss and increasing lifespan in animals, com extract on histone deacetylase activity. The results obtained prising a daily dosage of from betWeen 3 grams to 30 grams are shoWn in TABLE V Which folloWs: of phloriZion extract. 9. The dietary supplement of claim 8 Wherein said daily TABLE V dosage further comprises a unitary dosage of betWeen one Histone deacetylase gram and ten grams of phloriZin extract formulated for Polyphenol Concentration activity administration in three daily doses. 10. Amethod of treating or effecting disease or other body Phlorizin 100 micromolar 1.36 x baseline Phloretin 500 micromolar 1.94 x baseline conditions in an animal by modifying blood glucose and Catechins 500 micromolar 1.26*1.53 x baseline insulin levels through administration of compositions con Quercetin 500 micromolar 4.59 x baseline taining phloriZin extract standardiZed to a content of betWeen about 0.5% and about 99%. 11. The method of claim 10 Wherein said treating or These results demonstrate that components of apple extract effecting of disease or body conditions is the decreasing of increase histone deacetylase activity in manner consistent blood and insulin glucose levels. With the knoWn anti-aging effects of histone deacetylase 12. The method of claim 10 Wherein said treatment or induction. effecting of disease or body condition is the elimination of reactive hypoglycemia. [0035] The data illustrate that phloriZin extract decreases 13. The method of claim 10 Wherein said treating or the rate of aging through three separate mechanisms: As a effecting of disease or body conditions is the amelioration of caloric restriction mimetic to decrease glucose and insulin levels; by decreasing the formation of advanced glycation stress hyperglycemia. end products; and through increasing histone deacetylase 14. The method of claim 10 Wherein said treating or activity. effecting of disease or body conditions is the controlling of Weight changes in an animal. [0036] The phloriZin extract of the present invention pro 15. The method of claim 14 Wherein said controlling of vides bene?cial effects in the modi?cation of glucose trans Weight changes is the facilitation of Weight loss. port, blood and urine glucose levels and blood insulin levels. 16. The method of claim 15 Wherein said method further The phloriZin extract is also effective in producing Weight comprises the administration of said phloriZin extract, Which US 2006/0189512 A1 Aug. 24, 2006

is standardized to a concentration of about 40%, in a daily 22. The method of claim 10 Wherein said treating or dosage of from between about three grams to thirty grams. e?‘ecting of disease or body conditions is the formation of 17. The method of claim 14 Wherein said controlling of advanced glycosylation end products. Weight changes is the prevention of Weight gain. 23. The method of claim 10 Wherein said administration 18. The method of claim 10 Wherein said treating or of compositions containing phloriZin extract further com e?‘ecting of disease or body conditions is the prevention of prises administering said compositions from thirty minutes development of diabetes in patients With glucose intoler to one hour prior to consumption of food or a meal. ance. 24. The method of claim 10 Wherein said concentration of 19. The method of claim 18 Wherein said treatment further phloriZin extract in said composition is betWeen about 20% comprises the co-administration of diabetes-related pharma to about 40%. ceuticals selected from the group comprising insulin secre 25. The method of claim 10 Wherein said phloriZin extract togogues, insulin sensitiZers and alpha-glucosidase inhibi is extracted from the fruit, tWigs, bark and aerial parts of tors fruit trees, from the fruit and plant parts of straWberry plants, 20. The method of claim 10 Wherein said treating or and combinations thereof. e?‘ecting of disease or body conditions is the increasing of 26. The method of claim 15 Where the controlling of longevity and decreasing of onset or incidence of age-related Weight loss is mediated by selection of increased phloriZin diseases by decreasing glucose and insulin levels. extract administration to effect selected increased Weight 21. The method of claim 10 Wherein said treating or loss. e?‘ecting of disease or body conditions is the increasing of histone deacetylase activity.