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WO 2009/033103 Al (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 12 March 2009 (12.03.2009) WO 2009/033103 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 36/70 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, (21) International Application Number: CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, PCT/US2008/075499 EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, (22) International Filing Date: IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, 5 September 2008 (05.09.2008) LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, MY,MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, (25) Filing Language: English RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW (30) Priority Data: 60/970,784 7 September 2007 (07.09.2007) US (84) Designated States (unless otherwise indicated, for every (71) Applicant (for US only): BIONOVO, INC. [US/US]; kind of regional protection available): ARIPO (BW, GH, 5858 Horton Street, Suite 375, Emeryville, CA 94608 GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (US). ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, (72) Inventor; and FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, (75) Inventor/Applicant (for US only): COHEN, Isaac NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, [US/US]; 361 LaSaIIe Avenue, Piedmont, CA 94610 (US). CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). (74) Agent: GRUMBLING, Matthew, V.; Wilson Sonsini Goodrich & Rosati, 650 Page Mill Road, Palo Alto, CA Published: 94304-1050 (US). — with international search report (54) Title: ESTROGENIC EXTRACTS OF PUERARIA LOBATA WILLD, OHWI OF THE LEGUMINOSAE FAMILY AND USES THEREOF (57) Abstract: Extracts of various species of the Leguminosae family have estrogenic properties. For example, aqueous and ethano- lie extracts of Pueraria lobata Willd. Ohwi of the Leguminosae family species possess estrogenic properties in both ERa+ and ERβ+ cells. These estrogenic effects include estrogen response element (ERE) stimulation as well as tumor necrosis factor (TNF) repres- sion. Methods are provided for treating climacteric symptoms, breast and/or uterine cancer, and osteoporosis. ESTROGENIC EXTRACTS OF Pueraria Iobata WUId. Ohwi of the Leguminosae l amih AND USES THEREOF RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Patent Application No. 60/970,784, filed September 07, 2007, the contents of which are herein incorporated by reference in their entirety. FIELD OF THE INVENTION [0002] The present invention relates to plant extract compositions, and more particularly to compositions comprising extracts of plant species belonging to the species Pueraria lobata Willd. Ohwi of the Leguminosae family. The invention further relates to methods of using and methods of making such plant extract compositions. BACKGROUND [0003] Hormone replacement therapy (HRT) has been used successfully to treat a variety of conditions, such as osteoporosis, increased risk of cardiovascular disease in post-menopausal women and climacteric symptoms, such as hot flashes, decreased libido and depression. However, HRT with estradiol (E2), either alone or in combination with progestin, can lead to undesirable effects. In fact, a recent Women's Health Initiative (WHI) study was abruptly halted when preliminary results showed that HRT was associated with a 35% increased risk of breast cancer. [0004] Breast cancer can be treated or prevented by using a so-called selective estrogen receptor modulator (SERM), such as tamoxifen. (Before the approval of tamoxifen, breast cancer treatment of pre-menopausal women often included removing the ovaries in order to reduce the cancer-stimulating effect of estrogen.) Tamoxifen appears to selectively block the cancer-inducing effects of estrogen in breast tissues of pre-menopausal women. Another SERM, raloxifene, has been approved for treatment of osteoporosis as an alternative to estrogen replacement. In addition to selectively inducing estrogenic effects in bone tissue, long-term administration of raloxifene was also shown to be associated with reduction in the rate of breast cancer in the Multiple Outcomes of Raloxifene Evaluation (MORE) study. [0005] While SERMs such as tamoxifen and raloxifene provide selective reduction in estrogen's cancer- inducing effects in the breast, they are not without their risks. For example both tamoxifen and raloxifene therapy have been associated with increased incidence of hot flushes, and tamoxifen therapy has been shown to increase the risk of uterine (endometrial) cancer. [0006] Despite the success of estrogen replacement therapy in treating osteoporosis, coronary heart disease and climacteric symptoms, and of SERMs like tamoxifen and raloxifene in treating breast cancer and osteoporosis, there remains a need for compositions having estrogenic properties. Additionally, given the increasing cost of producing drug compounds, there is a need for additional estrogenic compositions that may be obtained from natural sources. [0007] Various cultivars of Pueraria lobata WMd. Ohwi of the Leguminosae family are grown in China in Henan, Hunan, Zhejiang and Sichuan provinces Various other varieties grow all over the world. The root is collected in the autumn and winter. It is washed clean and than sun dried. SUMMARY OF THE DSfVENTION [0008] The present inventor has identified a need for estrogenic compositions useful for the treatment of one or more disease states associated with the estrogen receptor. The inventor has also identified a need for estrogenic compositions that do not increase the risk or likelihood that a patient administered the compositions will suffer from another disease state associated with an estrogen receptor. The inventor has likewise recognized a need for an estrogenic composition that will reduce the risk of one or more estrogen receptor mediated disease states while, at the same time, treating another estrogen receptor mediated disease state. The inventor has also identified a need for estrogenic compositions that are readily obtained from natural sources, as well as a need for methods of making and using such estrogenic compositions. The disclosure herein meets such needs and provides related advantages as well. [0009] The invention provides a plant extract composition that contains an extract of a plant species of the species Pueraria lobata WHId. Ohwi of the Leguminosae family. Some embodiments provide an extract of a plant species selected from the taxonomic species Pueraria lobata WHId. Ohwi of the Leguminosae family. In some embodiments, the extract is either an aqueous extract, an ethanolic extract, a purified extract or a partitioned extract. In some embodiments, the extract is an ethanolic extract. Some embodiments provide a composition that contains an extract of a plant species of the species Pueraria lobata Willd. Ohwi of the Leguminosae family for use in the manufacture of a medicament. In some embodiments, the medicament possesses an estrogenic effect. In some embodiments, the estrogenic effect is at least one effect selected from the group consisting of: treating or preventing at least one climacteric symptom; treating or preventing osteoporosis; treating or preventing uterine cancer; and treating or preventing cardiovascular disease hi some embodiments, the estrogenic effect includes treating or preventing at least one climacteric symptom selected from the group consisting of treating or preventing hot flashes, insomnia, vaginal dryness, decreased libido, urinary incontinence and depression. In some embodiments, the estrogenic effect includes treating or preventing osteoporosis, hi some embodiments, the estrogenic effect includes treating or preventing hot flashes. In some embodiments, the estrogenic effect includes treating or preventing uterine cancer or breast cancer hi some embodiments, the estrogenic effect does not include increasing the risk of mammary hyperplasia, mammary tumor, uterine hyperplasia, uterine tumor, cervical hyperplasia, cervical tumor, ovarian hyperplasia, ovarian tumor, fallopian tube hyperplasia or fallopian tube tumor. In some embodiments, the estrogenic effect includes decreasing the risk of mammary hyperplasia, mammary tumor, uterine hyperplasia, uterine tumor, cervical hyperplasia, cervical tumor, ovarian hyperplasia, ovarian tumor, fallopian tube hyperplasia or fallopian tube tumor. [0010] Some embodiments provide the use of a composition of paragraph [0009] for the preparation of a medicament. In some embodiments, the medicament possesses an estrogenic effect hi some embodiments, the estrogenic effect is at least one effect selected from the group consisting of: treating or preventing at least one climacteric symptom; treating or preventing osteoporosis; treating or preventing uterine cancer; and treating or preventing cardiovascular disease. In some embodiments, the estrogenic effect includes treating or preventing at least one climacteric symptom selected from the group consisting of: hot flashes, insomnia, vaginal dryness, decreased libido, urinary incontinence, headache and depression. In some embodiments, the estrogenic effect includes treating
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