(12) Patent Application Publication (10) Pub. No.: US 2010/0323045 A1 Pischel Et Al
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US 20100323045A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0323045 A1 Pischel et al. (43) Pub. Date: Dec. 23, 2010 (54) EXTRACT FORMULATION OF OPUNTIA Related U.S. Application Data FCUSINDICA (60) Provisional application No. 61/002,058, filed on Nov. 6, 2007. (75) Inventors: Ivo Pischel, Rossbach (DE); Bjoern (30) Foreign Application Priority Data Feistel, Andernach (DE); Bernd Walbroel, Konigswinter (DE) Nov. 6, 2007 (EP) .................................. O7120081.0 Publication Classification Correspondence Address: (51) Int. Cl. OHLANDT, GREELEY, RUGGIERO & PERLE, A6IR 36/33 (2006.01) LLP A6IPL/04 (2006.01) ONE LANDMARKSQUARE, 10TH FLOOR A6IP3/00 (2006.01) STAMFORD, CT 06901 (US) (52) U.S. Cl. ........................................................ 424/767 (57) ABSTRACT (73) Assignee: Finzelberg GMBH & CO. KG A process for the preparation of an opuntia extract formula tion, comprising the steps of (21) Appl. No.: 12/741,562 a) extracting plant parts selected from fruit, fruit parts, and mixtures thereof using an extractant containing water and from 0 to 70% by weight of alcohols; (22) PCT Filed: Nov. 6, 2008 at least partially removing the extractant; b) extracting plant parts selected from cladodes, cladode (86). PCT No.: PCT/EP2008/06504.8 parts and mixtures thereof using an extractant contain ing water and from 0 to 70% by weight of alcohols; S371 (c)(1), at least partially removing the extractant; (2), (4) Date: Aug. 23, 2010 c) mixing together the extracts of step a) and b). Patent Application Publication Dec. 23, 2010 Sheet 1 of 2 US 2010/0323045 A1 In vivo Oral glucose tolerance test (n=6) s 500 ------ w -r Cadode extract according S. to Ex. 3b (5.9 mg/kg) S 4OO . Control NaCl Solution s -9. 3OO - S. www. toCladode Ex.3c extract (5.9 mg/kg) according g > -- - s . --. t. ------ 2OO 1. i o 1 OO O O -2O O 2O 40 60 8O 1 OO 12O 140 Time (min) Fig. 1 In vivo Course of insulin level in OGTT (n-6) E 4OO Cladode extract according to Ex. 3b (5.9 mg/kg) m - - - - - - Conto NaC Solution S. 3OO - - - Cadode extract according SS to Ex. 3C (5.9 mg/kg) S. 2OO d --- a | f : . ... -- - - - - - - - - - 5-src 1 OO O -20 O 20 4O 60 8O 1 OO 12O 14O Time (min) Fig. 2 Patent Application Publication Dec. 23, 2010 Sheet 2 of 2 US 2010/0323045 A1 -00052 C/o nw US 2010/0323045 A1 Dec. 23, 2010 EXTRACT FORMULATION OF OPUNTA fraction and a mucilage fraction (each about 10%). A gastro FCUSINDICA protective effect of the mucilage extract is described. No relation to a glucose- or lipid-metabolic activity is described. BACKGROUND 0011. Other than the applications described above, the 0001 1. Field of the Disclosure literature, including patent literature, describes the use of 0002 This disclosure relates to cactus pear extract formu plant extracts from cladodes of prickly pears for alcohol lations, methods for their manufacture and their use. Cactus induced hangovers (KR 2004-0094173), as a neuroprotective pear extract formulations have a positive effect on blood agent (KR 2003-0035974), as an immune stimulant (KR glucose levels and can be used for the treatment and preven 2002-0092021), for dermatological problems (JP 2002 tion of diabetes mellitus II. 0072130; KR 2003-0023398) and as a microbicide (U.S. Pat. 0003 2. Discussion of the Background Art No. 3,860,710; KR 2003-0023398). The fruits (cactus pears) 0004. The cactus pear (Opuntia spp., Opuntiaficus indica) are extracted and concentrated to obtain food colourings (be has for centuries been used in traditional medicine in the New talain, etc.) (KR 2003-0035974; Mo?hammer MR, Stintzing World, in South, Central and North America, and also in the FC, Carle R. Cactus Pear Fruits (Opuntia spp.): A Review of countries of the Mediterranean, North Africa and other areas Processing Technologies and Current Uses. 2006, J. PACD, for treating illnesses, for alleviating symptoms and for pre 1-25). venting metabolic disorders. (0012 DE 103 50 194 discloses the plant's flowers as an 0005 Stintzing FC and Carle R (Cactus stems (Opuntia extracted plant component which is neither cladode nor fruit. spp.) A review on their chemistry, technology, and uses. Mol. The ethanolic flower extract is reputed to be neuroprotective. Nutr. Food Res. 2005, 49, 175-194) describe a range of uses (0013 Wolfram RMetal. (Effect of prickly pear (Opuntia of cactus stems (cladodes), including anti-oxidant, anti-in robusta) on glucose- and lipid-metabolism in non-diabetics flammatory (including in ulcers), analgesic, hypoglycaemic, with hyperlipidemia—A pilot study), Wiener klinische anti-diabetic and blood lipid and cholesterollowering effects. Wochenschrift 114 (2002), 804-846 describe pectin as the Due to the pigmented betalain derivatives they contain, cactus mode of action of metabolic activity from fruit pulp and stated pears, the edible fruit of Opuntia species, have been described an insulin-lowering side-effect after administration of about as having uses as food-stuffs, in particular as food colouring 250 g fruits per day. concentrates, and as therapeutic remedies. A review by Livrea 0014 No synergistic anti-diabetic or hypoglycaemic MA and Tesoriere L (Health Benefit and Bioactive Compo activity has previously been ascribed to any combination of nents of the Fruits from Opuntiaficus-indica. J. PACD 2006, fruits, fruit juice or fruit components with cladodes or any 73-90) showed, in particular in the use of the edible parts of extracts thereof. the fruit and fruit juice, anti-oxidant activity, cardio-protec 0015 The object and purpose of the present disclosure is tive, anti-ulcer and hepato-protective effects, as well as a to reproducibly manufacture cactus pear extract preparations protective effect on nervous tissue and cancer prophylaxis. with improved characteristics, in particular an increased Antioxidant betalain derivatives with free radical scavenging hypoglycaemic effect. properties are cited as the bioactive Substances. 0016 Further, it makes use of novel, inexpensive plant 0006 Traditional use of Opuntia in type 2 diabetes melli components which are readily available and thus previously tus is limited to the use of fresh cladodes (young cactus unused raw materials. shoots), which are generally boiled, fried or grilled and eaten in quantities of up to 500 grams (Frati AC, Xilotl Diaz, N. SUMMARY Altamirano P. Ariza R, Lopez-Ledesma R.: The effect of two 0017 Surprisingly, it was found that this object can be sequential doses of Opuntia Streptacantha upon glycemia. achieved using a method for manufacturing cactus pear Arch Invest Med (Mex.), 1991, 333-6). extract preparation encompassing the steps 0007. In 1933 Gruwell CE and Preene HE described an 0018 a) extracting plant parts selected from fruit, fruit antidiabetic activity for an extract offleshy branches of Opun parts, and mixtures thereof using an extractant containing tia phaeacantha (U.S. Pat. No. 2,082,952). Neither active water and from 0 to 70% by weight of alcohols; components nor purification steps had been mentioned. They 0019 at least partially removing the extractant; disclosed the use of intense Solar radiated plants as a need for 0020 b) extracting plant parts selected from cladodes, effective and active products. cladode parts and mixtures thereof using an extractant con 0008 Even in relatively high dosages, dried, powdered taining water and from 0 to 70% by weight of alcohols; cladodes in pharmaceutical forms of administration Such as 0021 at least partially removing the extractant; tablets and capsules have a blood lipid reducing effect only 0022 c) mixing together the extracts of step a) and b). and are marketed solely for this purpose (www.neopuntia. 0023 The fruits, fruit parts, cladodes and cladodes parts com). are plant parts from Opuntia. 0009 Undefined cladode extracts produced using organic 0024. In one embodiment the method encompasses solvents have been described in the literature as having a 0025 1. extraction from raw materials a) fresh or dried hypoglycaemic effect. (Trejo-Gonzalez. A et al. A purified fruit skin (pomace or fruit residue following juice extraction) extract from prickly pear cactus (Opuntia fuliginosa) controls and/or fresh or dried cladodes or the residue of same follow experimentally induced diabetes in rats. Journal of Ethnop ing pressing, b) mixing the raw material with a hydroalco harmacology, 1996, 27-33.) holic extraction medium in order to obtain a raw extract, 0010 Galati EM et al. (Opuntia ficus indica (L.) Mill. where the hydroalcoholic extraction medium contains 0 to mucilages show cytoprotective effect on gastric mucosa in 70% vol alcohol: rat), Phytotherapy Research 21 (2007), 344-346 described an 0026. 2. at least partial removal of the alcoholic compo aqueous extraction of fresh cladodes, followed by a reprecipi nent of the raw extract in order to obtain a concentrated, tation of the extract in ethanol to receive a small pectin primarily aqueous or almost water-free thick extract; US 2010/0323045 A1 Dec. 23, 2010 0027. The extract preparation obtained may be processed: fruits and a 50:50 w/w mixture thereof manufactured in 0028 a) immediately for the manufacture of liquid formu accordance with the inventive method compared to a control/ lations (syrups, drops, drinks); glibenclamide. 0029 b) for filling soft gelatine capsules or 0030 c) with or without carriers to dried extracts. DETAILED DESCRIPTION OF THE PREFERRED 0031. In one embodiment, instead of an extract from fruits EMBODIMENT or fruit parts, juice from fruits of Opuntia is mixed with an 0037 According to the inventive method, individual cac extract from cladodes, cladode parts or mixtures thereof. tus pear raw materials or a mixture thereofare first extracted 0032. One object of the disclosure is the conversion of the using a hydroalcoholic extraction medium or pure water. The extracts in dried cactus pear extract preparations with stan plant material is usually chopped into Small pieces (8-12mm) dard pharmaceutical adjuvants into various pharmaceutical to speed up and increase the efficiency of extraction.