US 2014O161919A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0161919 A1 Thangavel et al. (43) Pub. Date: Jun. 12, 2014 (54) PLANT PARTS AND EXTRACTS HAVING Publication Classification ANTICOCCDAL ACTIVITY (51) Int. C. (71) Applicant: Kemin Industries, Inc., Des Moines, IA A61E36/49 (2006.01) (US) A61E36/85 (2006.01) A61E36/22 (2006.01) (72) Inventors: Gokila Thangavel, Hosur (IN); (52) U.S. C. Rajalekshmi Mukkalil, Cochin (IN); CPC ................. A61K 36/49 (2013.01); A61K 36/22 Haridasan Chirakkal, Nolambur (IN); (2013.01); A61K 36/185 (2013.01) Hannah Kurian, Benson Town (IN) USPC ........................................... 424/769; 424/725 (21) Appl. No.: 13/928,504 (57) ABSTRACT (22) Filed: Jun. 27, 2013 Natural plant parts and extracts of plants selected from the Related U.S. Application Data group consisting of Quercus infectoria, Rhus chinensis and (60) Provisional application No. 61/664,795, filed on Jun. Terminalia chebula containing compounds such as gallic 27, 2012. acid, derivative of gallic acid, gallotannins and hydrolysable tannins have been found to control coccidiosis in poultry and, (30) Foreign Application Priority Data more specifically, coccidiosis caused by Eimeria spp. The plant parts and natural extracts result in a reduction of lesion Jan. 23, 2013 (IN) ............................. 177/DELA2013 score, oocysts per gram of fecal matter and mortality. Patent Application Publication Jun. 12, 2014 Sheet 1 of 14 US 2014/O161919 A1 Positive control S Negative control Positive Control Quercus infectoria Patent Application Publication Jun. 12, 2014 Sheet 2 of 14 US 2014/O161919 A1 as a 3. Q3 is niecifia FIG. 3 3 9. - E. acervilia E. axifra E. ferrella & Corto & fece: Otro : Satiromycin 60 ppm N Quercus infectoria water extract 100 ppm n =6, p<0.05 FIG. 4 Patent Application Publication Jun. 12, 2014 Sheet 3 of 14 US 2014/O161919 A1 n = 3, p<0.05 in Sal my Quercus 60ppm 100 ppm infectori 50ppm 100ppm 200ppm FG. 6 n = 3, p<0.05 Patent Application Publication Jun. 12, 2014 Sheet 4 of 14 US 2014/O161919 A1 36 wneg ctrl m\npos ctrl *Q. infectoria 100 ppm 34 assG. infectoria 50ppm SS - 32 w YM saway assass Time (hours) FIG. 7 30 : & Neg Ctrl & POS Ctrl s Q. Infectoria 100 ppm N 25 : &Q. Infectoria 50 ppm ta 25 20 s E s 15 o s 5 10 s d : 5 : sess ŠsN O --------------------------------,s--------------,------------ WNSls-----------------Sr. O 10 20 30 40 50 60 70 80 90 100 Incubation time (hours) FIG. 8 Patent Application Publication Jun. 12, 2014 Sheet 5 of 14 US 2014/O161919 A1 36 Nneg ctrl Napos ctrl *::::: Q. infectoria 250 ppm 34 &Q. infectoria 100 ppm sasa Q. infectoria 50ppm 32 30 S ŠSS Sws N s sans. 28 ass ŠNaaS-i. 26 24 r 22 Time (hours) FIG. 9 40 N^neg ctrl &pos ctrl 35 . :x Q. infectoria 250 ppm NQ. infectoria 100 ppm 30 s&Q. infectoria 50 ppm 25 20 15 10 - 5 sssssssssss S s&w\ &Sissssssssssss &SS O 20 40 60 80 Incubation time (hours) FIG 10 Patent Application Publication Jun. 12, 2014 Sheet 6 of 14 US 2014/O161919 A1 8 . Haema„.“, !***–?2.*, •…” FIG 11 FIG. 12 Patent Application Publication Jun. 12, 2014 Sheet 7 of 14 US 2014/O161919 A1 ----| ;-->* Patent Application Publication Jun. 12, 2014 Sheet 8 of 14 US 2014/O161919 A1 i n=3, p<0.05, Correlation Coefficient= -0.982226 32 Nneg ctrl w$mpos ctrl & Gallic acid 10 ppm 30 28 & 2 6 ^ma& my s 24 T S. NSN & 22 20 2O 72 9 6 Time (hours) FG 16 Patent Application Publication Jun. 12, 2014 Sheet 9 of 14 US 2014/O161919 A1 wneg ctrl s 100 & NSnpos ctrl s 90 s as Gallic acid 10 ppm es R i 80 s N se R a. & 2 70 R ? s& s R 60 s s sS. s s s S s S s S.s s XS 50 s S s s s S s S s 40 - R s s Rs Ss sS s s s s - Rs s s s s R s s C S.s SS s SS s O 20 s s s s s Rw s & SS s S s SS s S s SS S s S Sa & xxs SSS S s s's S s SsssSS sawn\Š samaš s SSSSSSSSSSS s Šy - - - -:------------------------------------- ---x------------------x-----------Sys N.-----------------------------------------------------------------. S. O 20 40 60 80 100 Incubation time (hours) FIG. 17 36 x^neg ctrl &pos ctrl x:x Gallic acid 50 ppm 34 & Gallic acid 25 ppm w\Gallic acid 10 ppm 32 SS Ssss i 30 SSS Sm. Ssss SX 28 Ša NN 26 NN N N 24 YomSSX \xass. 22 Time (hours) FIG. 18 Patent Application Publication Jun. 12, 2014 Sheet 10 of 14 US 2014/O161919 A1 40 - as a neg ctrl Napos ctrl 35 gallic acid 50 ppm $Šs gallic acid 25ppm 30 *&^gallic acid 10 ppm 25 20 15 - 10 - 5 O rurururururururururururururuvurr-uur-rurr-uur-rurur------------------------- O 20 40 Incubation time (hours) FIG. 19 Patent Application Publication Jun. 12, 2014 Sheet 11 of 14 US 2014/O161919 A1 b &S S s O.5. C 8 8 O c - - - - - - - - - - - - E. ferreia E. acervuilia E. iiiaxina Š COtto Sece Cool & Sanomycin 60 ppi. & Galic acid 11 pm & Gallic acid 22 ppin & Galic acic 55 ppm 1.00E+07 1.00E+06 1.00E+05 1.00E+04 1.00E+03 1.00E+02 . Patent Application Publication Jun. 12, 2014 Sheet 12 of 14 US 2014/O161919 A1 &; }} } } } } } } } } } } } } } } }} } } } } } } } } } } } } } } } } } } } } ;~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~, FIG 22 Patent Application Publication Jun. 12, 2014 Sheet 13 of 14 US 2014/O161919 A1 36 &neg ctrl R Nanpos Ctrl T. chebula 250 ppm 34 NT. chebula 100 ppm wT.chebula 50ppm 32 9 30 5 S. N SS si Saxas 28 - sn \ s s s N\s \s s s N s ymna W 26 s N \ -- w Y s NN N& T 24 . to 20 72 96 Time (hours) FIG. 23 40 n^neg ctrl 2G wpos ctrl 35 T. chebula 250 ppm S NxT. chebula 100 ppm aw 30 &T. chebula 50 ppm Z s o S. 25 & in 20 s 3o 15 As 10 U 9. O 5 ss 0 O 2 O 40 60 8O 100 Incubation time (hours) FIG. 24 Patent Application Publication Jun. 12, 2014 Sheet 14 of 14 US 2014/O161919 A1 3 2.5 s 4. C 15i s - E. acervifa E. praxifra E. ferrella 8 COO 8 feted COO & Salinomycin 60 ppm & Rhus to ppm & Rhus 200 ppm & Rhus 500 ppm 6, p<0.05 : Terminalia chebula 1000 ppm FIG. 25 1.Eros Eros s iE-g4 e US 2014/01 6 1919 A1 Jun. 12, 2014 PLANT PARTS AND EXTRACTS HAVING the anti-inflammatory and antioxidant properties of the ANTICOCCDAL ACTIVITY proanthocyanidins, a condensed tannin rather than a hydrolysable tannin. 0001. This application claims priority to U.S. Patent Application Ser. No. 61/664,795, filed Jun. 27, 2012 and 0006 Naidoo et al. teach an in vivo study using four plants selected based on their antioxidant activity (Naidoo et al. The Indian Application No. 177/DEL/2013, filed Jan. 23, 2013, value of plant extracts with antioxidant activity in attenuating both of which are incorporated herein by this reference. coccidiosis in broiler chickens. Veterinary Parasitology. 153: BACKGROUND OF THE INVENTION 214-219; 2008). They observed that one of the plants (Tul baghia violacea) reduced the Eimeria oocyst counts in the 0002 The present invention relates generally to the con chicken excreta and they speculate that this effect could be trol of coccidiosis and, more specifically, to the application of due to the antioxidant compound S (methylthiomethyl) cys plant parts, plant extracts and compounds to control coccidi teine sulfoxide. osis in poultry and other animals. 0007 McDougald et al. describe the use of a muscadine 0003 Coccidiosis is a major disease in the poultry indus pomace to enhance resistance to coccidiosis in broiler chick try and according to a recent Survey, it is estimated that the ens (McDougald et al. Enhancement of Resistance to Coc global impact is greater than $3 billion USD annually (world cidiosis and Necrotic Enteritis in Broiler Chickens by Dietary poultry.net/Broilers/Health/2009/9/In-Ovo-vaccination Muscadine Pomace. Avian Diseases. 52: 646-651; 2008). against-coccidiosis-WP006949W/ accessed Jun. 18, Muscadine pomace is a by-product of grapes used in wine 2013). Coccidiosis is caused by a protozoan parasite, namely production. They make no mention of efficacy of any specific Eimeria, belonging to the phylum Apicomplexa, and the fam compounds in the pomace. The proposed anti-coccidial activ ily Eimeriidae (Clare, R.A and Danforth, H. D (1989). Major ity differs significantly from the activities proposed by Wang histocompatibility complex control of immunity elicited by et al. and Naidoo et al. genetically engineered Eimeria tenella (Apicomplexa) anti gen in chickens. Infection and immunity, 57 (3): 701-705). SUMMARY OF THE INVENTION The parasite invades the gut cells and causes necrosis in the intestine which leads to malabsorption, diarrhea, morbidity, 0008. The present invention consists of the identification reduction of weight gain, poor feed conversion, and, in severe and use of plant parts and plant extracts effective in the cases, mortality (Williams, R. B (2005). Intercurrent coccidi control of coccidiosis in animals, particularly in poultry. Spe osis and necrotic enteritis of chickens: Rational, integrated cifically, plant parts and natural extracts of Quercus infecto disease management by maintenance of gut integrity. Avian ria, Rhus chinensis gall nut, Terminalia chebula fruit have Pathology, 34(3), 159-180).