US 2005O226941A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0226941A1 Ogawa et al. (43) Pub. Date: Oct. 13, 2005 (54) COMPOSITION FOR CONTROLLING (22) Filed: Jan. 6, 2005 EXCESSIVE CALORIE INTAKE-INDUCED DISORDER, FOOD PRODUCT FOR (30) Foreign Application Priority Data CONTROLLING EXCESSIVE CALORIE INTAKE-INDUCED DISORDER, SKIN Apr. 7, 2004 (JP)...................................... 2004-113027 PREPARATION FOR EXTERNAL USE FOR CONTROLLING Publication Classification (75) Inventors: Hiroshi Ogawa, Tondabayashi-shi (JP); (51) Int. Cl. ................................................. A61K 35/78 Toshio Mitsunaga, Kyoto-shi (JP); (52) U.S. Cl. .............................................................. 424/725 Toshinori Kamisako, Sakai-shi (JP); Yukio Kawamura, Nara-shi (JP) (57) ABSTRACT Correspondence Address: DARBY & DARBY PC. P. O. BOX 5257 A composition contains 0.1 to 10 g of dried Hercampuri extract obtained by extracting the essence of dried whole NEW YORK, NY 10150-5257 (US) Hercampuri plant with 60 to 80% aqueous ethanol. It has a (73) Assignee: Towa Shoji Kabushiki Kaisha, Tokyo function of prevention or curative treatment of lifestyle (JP) related disorders induced by accumulation of Visceral fat resulting from excessive calorie intake. It is useful for (21) Appl. No.: 11/031,732 maintaining, improving and promoting health. 18.0 15. O 12.. O 9. O 6.0 3.0 0.0 2.5 5.0 12.5 25. O 50.0 125. O 250. O HERCAMPUR EXTRACT CONCENTRATION CL1 g/ml) Patent Application Publication Oct. 13, 2005 Sheet 1 of 10 US 2005/0226941 A1 18.0 15.0 12.. O 9. O 6.0 3.0 0.0 2.5 5.0 12.5 25. O 500 125. O 250. O HERCAMPUR EXTRACT CONCENTRATION (11 g/ml) F I. G. 1 10. 0 8.0 6.0 4.0 2.0 0.0 0.25 0.50 - 25 2.5 5.00 12.50 25.00 MANGIFERIN CONCENTRATION (p1 g/ml) F I. G. 2 Patent Application Publication Oct. 13, 2005 Sheet 2 of 10 US 2005/0226941 A1 18. O 15.0 - 12.. O 9. O 6.0 3.0 0.0 2.5 5. O 12.5 25. O 50. O 125. O 250. O HERCAMPUR EXTRACT CONCENTRATION (1 g/ml) F I. G. 3 10. 0 8. O 6.0 4. O 2.. O 0.0 0.25 0.50 1 25 2.5 5.00 12.50 25.00 MANGIFERIN CONCENTRATION (u g/ml) F I. G. 4 Patent Application Publication Oct. 13, 2005 Sheet 3 of 10 US 2005/0226941 A1 80.0 60. O 40.0 20. O 0.0 2.5 5.0 12.5 25. O 50.0 125. O 250. O HERCAMPUR EXTRACT CONCENTRATION (1 g/ml) F I. G. 5 80.0 60. O 40... O 20. 0 0.0 0.25 0.50 1 25 2.5 5.00 12.50 25.00 MANG|FERIN CONCENTRATION (11 g/ml) F I G. 6 Patent Application Publication Oct. 13, 2005 Sheet 4 of 10 US 2005/0226941 A1 300.0 y=0. 121e0. 102 R2=O. 9306 250. O IC50=19.8C tug/ml) 200.0 150.0 100.0 50.0 O. O. 20.0 30.0 40. O 50.0 60. O 700 80.0 INHIBITORY RATIO (96) F I. G. 7 80 y=0.6946X-6. 6013 R2-0. 8573 O 20 40 60 80 INHIBITORY RATO BY HERCAMPUR EXTRACT (%) F I. G. 8 Patent Application Publication Oct. 13, 2005 Sheet 5 of 10 US 2005/0226941 A1 GLUCOSDASE INHIBITORY ACT WITY 130 120 O 100 90 80 70 60 50 40 O 3. 125 6.25 12.5 25 50 FINAL CONCENTRATION (1 M) F I. G. 9 Patent Application Publication Oct. 13, 2005 Sheet 6 of 10 US 2005/0226941 A1 LPD CONTENT IN WHOLE LIVER LETO-CONTROL 1000 OLETF-CONTROL a 6000 % HERCAMPURI o ACARBOSE N6 g 5000 S E. b Š 4000 N F I. G. 1 O (MEAN OF THE 5 RATS CONSTITUTING EACH GROUP – STANDARD ERROR OF THE MEAN) -H LET0-CONTROL -OH OLETF-CONTROL 900 -A- HERCAMPUR 850 -0- ACARBOSE 800 750 T. VVV-Ves/ 2 R A 700? 650 600 550 500 O 4 8 12 16 20 24, 28 32 36 40 44 FEED ING PERIOD DAYS) F I. G. 1 1 Patent Application Publication Oct. 13, 2005 Sheet 7 of 10 US 2005/0226941 A1 AMOUNT OF FOOD INTAKE (MEAN OF THE 5 RATS CONSTITUTING EACH GROUP STANDARD ERROR OF THE MEAN) - H. LEO-CONTROL -O-OLETF-CONROL 80 - A HERCAMPUR 70 -- ACARBOSE 2 6 10 14 18 22 26 30 34 38 42 FEED ING PERIOD DAYS) F I. G. 1 2 CHOLESTEROL (MEAN OF THE 5 RATS CONSTITUTING EACH GROUP – STANDARD ERROR OF THE MEAN) LETO-CONTROL SOLETF-CONTROL HERCAMPUR ACARBOSE Patent Application Publication Oct. 13, 2005 Sheet 8 of 10 US 2005/0226941 A1 PHOSPHOLPD EAN OF THE 5 RATS CONSTITUTING EACH P STANDARD ERROR OF THE MEAN) NTROL a a, b R •HØ aN ·?-o% %= F I G. 1 4 TRGLYCERIDE (MEAN OF THE 5 RATS CONSTITUTING EACH GROUP – STANDARD ERROR OF THE MEAN) 250 ETO-CONTROL OLETF-CONTROL HERCAMPUR ACARBOSE VLDL LDL HDL F I G. 1 5 Patent Application Publication Oct. 13, 2005 Sheet 9 of 10 E](110VALIWABBHH)[H]NOBISHTOHOHNIT [EI]TOHBISHTOHOHNIT-SISVIHIITETOHOD US 2005/0226941 A1 Oct. 13, 2005 COMPOSITION FOR CONTROLLING EXCESSIVE generation to generation from Pre-Inca times, as an effective CALORIE INTAKE-INDUCED DISORDER, FOOD cure-all for Suppressing or alleviating Stomach colic, chronic PRODUCT FOR CONTROLLING EXCESSIVE gastritis, and liver functions disorders. It is known that CALORIE INTAKE-INDUCED DISORDER, SKIN Hercampuri has been effective in revitalizing kidney/liver PREPARATION FOR EXTERNAL USE FOR functions, treating hepatitis, lowering malaria fever, purify CONTROLLING ing blood, and Stimulating bile Secretions, as well as antidia betic effect. Hercampuri is typically taken in the form of a INCORPORATION BY REFERENCE health tea, which is made by brewing whole dried Hercam puri plants. 0001. The present application claims priority under 35 U.S.C. S.119 to Japanese Patent Application No. 2004 0007 Xanthone derivatives are known to be among the 113027 filed on Apr. 7, 2004. The content of the application principal components of Hercampuri, among which Bellidi is incorporated herein by reference in its entirety. folin is found in the largest amounts. 0008 AS is described, for example, by P. Basnet and three TECHNICAL FIELD OF THE INVENTION other members in P. 507-511 of Planta Medica (Germany), 1994, Vol. 60 (“Bellidifolin obtained from Swertia japonica 0002 The present invention relates to a composition, a is highly effective in reducing blood Sugar levels in rats with food product, a skin preparation for external use, and a streptozotocin (STZ)-induced diabetes”) and by P. Basnet controlling agent, each of which contains, at least, Hercam and four other members in P. 401-405 of Planta Medica puri and has a function of controlling disorders induced by (Germany), 1995, Vol. 61 (“Bellidifolin is effective in reduc excessive calorie intake. ing blood Sugar levels by enhancing intake of glucose into fibroblast in rats with streptozotocin (STZ)-induced diabe BACKGROUND OF THE INVENTION tes”), it is widely known that Bellidifolin has a function of 0003. In recent years, Japanese dietary habits have exhib reducing blood Sugar levels in Streptozotocin (STZ)-induced ited an increase in the consumption of excessive fat or diabetic rats. calories as a result of changes in lifestyles, including the 0009. Mangiferin is another Xanthone derivative con Westernization of dietary habits. This has resulted in a sharp tained in Hercampuri. AS is described, for example, by H. increase in the morbidity of lifestyle-related diseases, Such Ichiki H and six other members in P. 1389-1390 of Biologi as hyperlipidemia, obesity, hypertension, and diabetes. Vari cal Pharmaceutical Bulletin (Japan), 1998, Vol. 21 ous remedies are used to treat hypertension, high choles (“Mangiferin is a novel antidiabetic compound”), it is terol, and diabetes, all of which are typical examples of known that Mangiferin has a function of reducing blood lifestyle-related diseases. AS described in, for example, Sugar levels and increasing insulin Sensitivity in KK-Ay Japanese Patent Laid-open Nos. 2002-363095, O6-345664, mice, which are regarded as a model of Type 2 diabetes. and 06-135839, effectiveness of these respective remedies are accepted to a certain level. 0010. However, the effects of Hercampuri have not yet been clearly proved nor have physiological functions of the 0004. However, these therapeutics target sick people, in components of Hercampuri been clarified. The aforemen other words those who have an disorder, and have not inconsiderable adverse effects, resulting in Significant resis tioned functions of Hercampuri against diabetes, too, have tance regarding long-term usage. Therefore, there is a great not been made clear. demand for development of a functional food product that is 0011. In view of the problems described above, an object a Safe, non-medicinal agent with Superior effectiveness in of the invention is to provide a composition, a food product, prevention and curative treatment of lifestyle-related dis a skin preparation for external use, and a controlling agent, eases and intended for people who are borderline patients for each of which contains, at least, Hercampuri and has a Such diseases. However, no product has ever been developed function of controlling disorders induced by excessive calo to Satisfy this demand completely. At present there is a great rie intake. demand for development of a composition that is effective in the prevention and curative treatment of lifestyle-related SUMMARY OF THE INVENTION diseases, and in particular, that has curative properties 0012. A composition for controlling disorders induced by against diabetes.