US010729714B2 ( 12 ) United States Patent ( 10 ) Patent No.: US 10,729,714 B2 Kristiansen et al. (45 ) Date of Patent : Aug. 4 , 2020 ( 54 ) BASIDIOMYCETE - DERIVED CREAM FOR (58 ) Field of Classification Search None TREATMENT OF SKIN DISEASES See application file for complete search history . ( 71 ) Applicant: Glycanova AS , Fredrikstad (NO ) ( 56 ) References Cited ( 72 ) Inventors : Bjørn Kristiansen , Fredrikstad (NO ) ; U.S. PATENT DOCUMENTS Anne Torill Hovland , Borgenhaugen 5,997,875 A 12/1999 Zhou et al. (NO ) 7,514,085 B2 4/2009 Kristiansen 7,682,615 B2 3/2010 Kristiansen ( 73 ) Assignee : GLYCANOVA AS , Gamle Frederikstad 7,947,283 B2 5/2011 Tu et al. (NO ) 8,758,768 B2 6/2014 Kristiansen 9,072,776 B2 7/2015 Kristiansen 9,249,438 B2 2/2016 Kristiansen ( * ) Notice : Subject to any disclaimer , the term of this 10,471,135 B2 11/2019 Kristiansen patent is extended or adjusted under 35 2008/0160043 A1 7/2008 Kim et al . U.S.C. 154 ( b ) by 358 days. 2017/0304415 Al 10/2017 Kristiansen (21 ) Appl. No .: 14 / 766,811 FOREIGN PATENT DOCUMENTS PCT Filed : JP 60-188402 9/1985 ( 22 ) Feb. 10 , 2014 JP 2006241130 9/2006 KR 20090002678 A 1/2009 ( 86 ) PCT No .: PCT / IB2014 /058878 KR 20100066694 A 6/2010 $ 371 ( c ) ( 1 ) , (2 ) Date : Aug. 10 , 2015 OTHER PUBLICATIONS Chen et al ., “ Effects of Ganoderma lucidum and it combined with (87 ) PCT Pub . No .: WO2014 / 122627 Radix Salviae Miltiorrhizae , Radix Bupleuri, and Fructus Schisandrae PCT Pub . Date : Aug. 14 , 2014 Chinensis respectively on experimental hepatic injuries in mouse ” , Acta Academiae Medicinae Militaris Tertiae , May 2001, vol. 23 , (65 ) Prior Publication Data No. 5 , pp . 567-570 . ( Including Assisted human translation ) . Kagaku to Seibutsu , 1985 , vol . 23 , No. 12 , pp . 797-802 . ( Including US 2016/0015734 A1 Jan. 21 , 2016 English translation of relevant part ) . Mizuno et al ., “ Fractionation , Structural Features and Antitumor Activity of Water -Soluble Polysaccharide from “ Reishi” the Fruit Body ofGanoderma lucidum ” , Nippon Nogeikagaku Kaishi, 1984 , Related U.S. Application Data vol . 58, No. 9 , pp . 871-880 . (English abstract including English (60 ) Provisional application No.61 / 763,014, filed on Feb. translation of relevant part of article provided ) . Mizuno et al ., “ Fractionation , Chemical Modification and Antitu 11 , 2013 . mor Activity of Water - Insoluble Polysaccharides of the Fruiting Body of Ganoderma lucidum ” , Nippon Nogeikagaku Kaishi , 1985 , ( 30 ) Foreign Application Priority Data vol. 59 , No. 11, pp . 1143-1151 . (English abstract including English translation of relevant part of article provided ) . Feb. 11 , 2013 (DK ) 2013 70070 Mizuno et al ., “ Reishi , Ganoderma lucidum and Ganoderma tsugae : Bioactive Substances and Medicinal Effects ” , Food Reviews Inter (51 ) Int . Cl. national, 1995 , vol. 11 , No. 1 , pp . 151-166 . A61K 8/99 (2017.01 ) Rop et al. , “ Beta - glucans in higher fungi and their health effects ” , A61K 31/716 ( 2006.01 ) Nutrition Reviews, 2009 , vol. 67 , No. 11 , pp . 624-631. A61K 36/07 ( 2006.01 ) Zhou et al. , “ Ganodermataceae : Natural products and their related A61K 31/728 ( 2006.01 ) pharmacological functions” , The American Journal of Chinese A61K 9/00 (2006.01 ) Medicine , 2007, vol. 35 , No. 4 , pp . 559-574 . A61K 9/06 ( 2006.01) A61K 35/644 ( 2015.01 ) * cited by examiner A61K 47/06 (2006.01 ) Primary Examiner — Amy L Clark A61K 47/10 ( 2017.01) (74 ) Attorney, Agent, or Firm Merchant & Gould P.C. A61K 47/12 ( 2006.01 ) A61K 47/26 ( 2006.01 ) (57 ) ABSTRACT A61K 47/44 ( 2017.01 ) An extract of a liquid culture of Ganoderma lucidum is A61K 9/70 ( 2006.01) provided . The production process encourages the growing ( 52 ) U.S. CI. mycelium to export bioactive compounds such as beta CPC A61K 31/716 (2013.01 ) ; A61K 9/0014 glucans into the surrounding liquid . Thus, the beta glucan is (2013.01 ) ; A61K 9/06 ( 2013.01) ; A61K 31/728 soluble and easily absorbed . More importantly , the produc (2013.01 ) ; A61K 35/644 (2013.01 ) ; A61K tion process allows the beta glucan to retain its triple helix 36/07 (2013.01 ) ; A61K 47/06 ( 2013.01 ) ; A61K structure which is required to maintain a very high bioactive 47/10 (2013.01 ) ; A61K 47/12 (2013.01 ) ; A61K efficacy . The beta glucans from Ganoderma lucidum can be 47/26 (2013.01 ) ; A61K 47/44 (2013.01 ) ; A61K used in a cream for treatment of psoriasis . 9/0021 ( 2013.01) ; A61K 9/7023 (2013.01 ) 17 Claims, 25 Drawing Sheets U.S. Patent Aug. 4 , 2020 Sheet 1 of 25 US 10,729,714 B2 Figure 1 A Notreatment B 20 07 treatmentNo U.S. Patent Aug. 4 , 2020 Sheet 2 of 25 US 10,729,714 B2 Figure 2A Limbs before treatment Limbs after 3 months treatment U.S. Patent Aug. 4 , 2020 Sheet 3 of 25 US 10,729,714 B2 Figure 2B Limbs before treatment Limbs after treatment 3 months 1 month U.S. Patent Aug. 4 , 2020 Sheet 4 of 25 US 10,729,714 B2 Figure 3 A : Skin on human leg before treatment B : Skin on same human leg after treatment U.S. Patent Aug. 4 , 2020 Sheet 5 of 25 US 10,729,714 B2 Figure 4 A ) Patient BH : Right elbow pre and post treatment B ) Patient BH : Left elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 6 of 25 US 10,729,714 B2 Figure 4 continued C ) Patient RA : Right elbow pre and post treatment D ) Patient RA : Left elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 7 of 25 US 10,729,714 B2 Figure 4 continued E ) Patient RA : Right knee pre and post treatment F ) Patient RA : Left knee pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 8 of 25 US 10,729,714 B2 Figure 4 continued G ) Patient JM : Right elbow pre and post treatment H ) Patient JM : Left elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 9 of 25 US 10,729,714 B2 Figure 4 continued 1 ) Patient JM : Right elbow pre and 1 month post treatment J ) Patient JM : Left elbow pre and 1 month post treatment U.S. Patent Aug. 4 , 2020 Sheet 10 of 25 US 10,729,714 B2 Figure 4 continued K ) Patient JM : Right calf pre and post treatment L ) Patient Pl: Right elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 11 of 25 US 10,729,714 B2 Figure 4 continued M ) Patient Pl: Left elbow pre and post treatment AN N ) Patient JS : Right elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 12 of 25 US 10,729,714 B2 Figure 4 continued 0 ) Patient JS : Left elbow pre and post treatment P ) Patient NM : Right elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 13 of 25 US 10,729,714 B2 Figure 4 continued Q ) Patient NM : Left elbow pre and post treatment R ) Patient GY: Elbows pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 14 of 25 US 10,729,714 B2 Figure 4 continued S ) Patient SG : Right elbow pre and post treatment T ) Patient SG : Left elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 15 of 25 US 10,729,714 B2 Figure 4 continued U ) Patient GO : Right elbow pre and post treatment V ) Patient GO : Left elbow pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 16 of 25 US 10,729,714 B2 Figure 4 continued W ) Patient CB : Left elbow pre and post treatment X ) Patient PK : Right knee pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 17 of 25 US 10,729,714 B2 Figure 4 continued Y ) Patient PK : Left knee pre and post treatment M Z ) Patient CB : Right knee pre and post treatment U.S. Patent Aug. 4 , 2020 Sheet 18 of 25 US 10,729,714 B2 Figure 5 Persent of total, reduction of itching 2 weeks Nissing Wreduction Figure 6 Percent of total , scaling , 2 weeks 250 200 de 15,0 10.0 5,0 20 % 80 % Missing % Reduction U.S. Patent Aug. 4 , 2020 Sheet 19 of 25 US 10,729,714 B2 Figure 7 Percent of total, redness 2 weeks 40,0 35.0 30.0 25.0 e 20,0 15,0 10,0 5.0 % 60 % 100 % Mssing % redution Figure 8 Percent of subjects with reduction of itching 4 weeks 25,0 15,0 0,0 20 % 1. 60 % 100 % Missing % reduction U.S. Patent Aug. 4 , 2020 Sheet 20 of 25 US 10,729,714 B2 Figure 9 Percent of total, scaling 4 weeks 25,0 20.0 15,0 Percent 10,0 5,0 0.0 0 % 20 % 40 % 60 % 100 % Missing ului% Reduction Figure 10 Percent of total, redness 4 weeks 30,0 25,0 15,0 %reduction 10,0 5,0 0,0 1 0 % 20un % 40 % 60 % 80 % 100 % Missing Percent U.S. Patent Aug. 4 , 2020 Sheet 21 of 25 US 10,729,714 B2 Figure 11 Percent of subjcts with reduction in itching at 2 and 4 weeks 2 weeks $ 4 weeks 30,0 25,0 20.0 Percent 15.0 10,0 0.0 0 % 20 % 40 % 60 % 80 % 100 % Missing % Reduction Figure 12 Percent of total after 2 and 4 weeks , scaling $ 2 weeks & 4 weeks 300 25.0 20.0 Percent 15,0 10.0 5.0 0,0 0 % 20 % 40 % 60 % 80 % 100 % Missing % reduction U.S. Patent Aug.