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US00877 1763B2

(12) Patent (10) Patent No.: US 8,771,763 B2 Asiedu et al. (45) Date of Patent: Jul. 8, 2014

(54) COMPOSITION FORTREATING AIDS AND 2004 as R 38 8. AsSiedlu et alal. ASSOCATED CONDITIONS 2010/0266715 A1 10, 2010 Asiedu et al. (71) Applicant: Ward-Rams. Inc., Bridgewater, NJ FOREIGN PATENT DOCUMENTS WO 98.25633 A2 6, 1998 (72) Inventors: William Asiedu, Accra (GH); Frederick WO 9951249 A1 10, 1999 Asiedu, Accra (GH); Manny Ennin, W E. A. 3.38. Accra (GH); Michael Nsiah Doudu, Accra (GH); Charles Antwi Boateng, OTHER PUBLICATIONS Accra (GH); Kwasi Appiah-Kubi, Accra (GH); Seth Opoku Ware, Accra (GH): "Alstonia. The List.” http://www.theplantlist.org/brows/A? Debrah Boateng. Accra (GH): Kofi /Alstonia, accessed May 9, 2013, 3 pages. Amplim, Accra (GH); William Owusu, “. .” http://www.theplantlist.org/brows/A? Accra (GH); Akwete Lex Adjei, . Anogeissus, accessed May 9, 2013, 2 pages. Bridgewater, NJ (US) “Cleistopholis—The Plant List.” http://www.theplantlist.org/brows/ A? Annonaceae/Cleistopholis, accessed May 9, 2013, 2 pages. (73) Assignee: Wilfred-Ramix, Inc., Bridgewater, NJ “Combretum. The Plant List.” http://www.theplantlist.org/brows/ (US) A/Combretacaea/Combretum, accessed May 9 2013, 13 pages. “Dichapetalum—The Plant List.” http://www.theplantlist.org/ (*) Notice: Stil tO E. distic th t brows/A/Dichapetalaceae/Dichapetalum, accessed May 9, 2013, 7 patent 1s extended or adjusted under pageS. U.S.C. 154(b) by 0 days. ". The Plant List.” http://www.theplantlist.org/brows/ A? Apocynaceae/Gongronema, accessed May 9, 2013, 2 pages. (21) Appl. No.: 13/949,613 "Strophanthus (plant )—Britannica Online Encyclopedia.” 1-1. http://www.britannica.com/EBchecked/topic/56953.5/Strophanthus, (22) Filed: Jul. 24, 2013 accessed May 9, 2013, 2 pages. O O “Uvariastrum. The Plant List.” http://www.theplantlist.org/brows/ (65) Prior Publication Data A? Annonaceae/Uvariastrum, accessed May 9, 2013, 2 pages. US 2014/OO23731 A1 Jan. 23, 2014 (Continued)

Related U.S. Application Data Primary Examiner — Susan Hoffman (60) Division of application No. 12/828,956, filed on Jul. 1, (74) Attorney, Agent, or Firm – Frommer Lawrence & 2010, now abandoned, which is a continuation of Haug LLP; Marilyn Matthes Brogan: Kathleen N. Ehrhard application No. 10/902,993, filed on Jul.30, 2004, now applicationPat. No. 7,749,544, No. 10,241,973, which filedis aon continuation Sep. 12, 2002, of (7) ABSTRACT now abandoned. An Aids and associated conditions related to Aids treating (51) Int. Cl compositions is disclosed. The compositions comprise: a A. iK s6/2 (2006.01) medicament selected from an extract of at least one of the A6 IK 36/22 (2006.015 following plant families: Apocynaceae (Pleioscarpa Bicar A6 IK36/86 (2006.015 pellata); Annonaceae (Cleistopholis Patens); Dichapetal A6 IK 36/24 (200 6,015 aceae (Dichapetehan Madagasca Riense); Annoceae 52) U.S. C (Uvaristrum Pierreanum); Cynocynaceae (Strophantus Gra (52) jSpC 424f725 tus); Asclepiadaceae (Gongronema Latifolium); Combreta ... ." grrrrr. ceae (Combretum Racemosum); Apocynaceae (Alostonia (58) Field of Classification Search Boonei); (Alternanthera Pungens); Aroceae CPC ...... A61K 36/00; A61K 2300/00 (Anchomanes Differmis); Cyperaceae (Seleria Voivinil); USPC ...... 424/725, 769 (Lannea Acida); Bignodaceae (Kigelia Afri See application file for complete search history. cana); (Ceiba Pentanota); Anarcardiaceae (56) References Cited ( Micraster); Bombacaceae (Bombax Bounopo zense): Anarcardiaceae (Spondias Mombin); U.S. PATENT DOCUMENTS ( ); a glyceryl ester of any of the foregoing extracts; a saponin of any of the foregoing extracts; an alka 4,761,286 A 8/1988 Hiji loid of any of the foregoing extracts; a protein of any of the 4,923,697 A 5, 1990 Albeck et al. foregoing extracts; a fat of any of the foregoing extracts; a 4,940,726 A 7, 1990 Pettit et al. 5,227,383 A 7, 1993 Clark et al. Sugar of any of the foregoing extracts; and any mixture of any 5,545,623 A 8, 1996 Matsumori of the foregoing. 5,607.673 A 3/1997 Bashengezi 5,919,460 A 7/1999 Ingram 6,132,725 A 10, 2000 Kadono et al. 2 Claims, No Drawings US 8,771,763 B2 Page 2

(56) References Cited Engler, A. et al., “Die Naturlichen: Pflanzenfamilien.” 1897, p. 349. Ginsberg, et al., “Challenges in tuberculosis drug research and devel OTHER PUBLICATIONS opment.” Nature Medicine, vol. 13, No. 3, Mar. 2007, pp. 290-294. Keshinro, O. O., “The Unconventional Sources of Ascorbic Acid in Akah, P. A. et al., “Evaluation of Nigerian Traditional Medicines: 1. the Tropics.” Nutrition Reports International, vol. 31, No. 2, Feb. Used for Rheumatic (Inflammatory) Disorders,” Journal of 1985, pp. 381-387. Ethnopharmacology, vol. 42, 1994, pp. 179-182. Njoku, C. J. et al., “The Anthelmintic Activities of Pleiocarpa Atindehou, K. K. et al., “Evaluation of the Antimicrobial Potential of bicarpellata Aqueous Extract.” Fitoterapia, vol. 67, No. 4, 1996, Medicinal Plants from the .” Phytotherapy Research, vol. 16, Aug. 2002, pp. 497-502. pp. 339-343. Boyom, F. F. et al., “Aromatic plants of tropical central . Part Ojewole, J. A. O., “Studies on the Pharmacology of Echitamine, and XLIII: volatile components from Uvariastrum pierreanum Engl. Alkaloid from the Stem Bark of Alstonia boomei L. (Apocynaceae).” (Engl. & Diels) growing in .” Flavour and Fragrance Jour International Journal of Crude Drug Research, vol. 22, No. 3, 1984, nal, vol. 18, 2003, pp. 296–298. pp. 121-143. Breteler, F. J., “Novitates Gabonenses 47. Another new Sanogo, R. et al., “Evaluation of Malian Traditional Medicines: Dichapetalum (Dichapetalaceae) from .” Adansonia, vol. 25. Screening for Antimicrobial Activity.” Phytotherapy Research, vol. No. 2, 2003, pp. 223-227. 12, 1998, pp. S154-S156. Calderón et al., “Evaluation of Diuretic Activity of Alteranthera Sultana, S. et al., “A Flavanone from Lannea acida.” Phytochemistry, pungens Extract in Rats.” Phytotherapy Research, vol. 11, 1997, pp. vol. 25, No. 4, 1986, pp. 963-964. 606-608. International Search Report for International Patent Application No. Duke, J. A. et al., “Handbook of Medicinal Herbs, Second Edition.” PCT/US2003/028295 mailed May 17, 2004. CRC Press, USA, 2002, pp. 364, "Abbreviations” section, 815-819, International Preliminary Report on Patentability for International 821-827. Patent Application No. PCT/US2003/028295 mailed Dec. 21, 2004. US 8,771,763 B2 1. 2 COMPOSITION FORTREATING AIDS AND interpreted, and highly specific. Other manifestations of ASSOCATED CONDITIONS HTLV-II/LAV infections than those currently proposed to be reported are less specific and less likely to be consistently CROSS REFERENCE TO RELATED reported nationally. Milder disease associated with HTLV-III/ APPLICATIONS LAV infections and asymptomatic infections may be report able in some states and cities but will not be nationally report The present application is a Divisional of U.S. patent appli able. Because persons with less specific or milder cation Ser. No. 12/828,956, filed Jul. 1, 2010, now aban manifestations of HTLV-III/LAV infection may be important doned, which is a Continuation of U.S. patent application Ser. in transmitting the virus, estimates of the number of Such No. 10/902,993, filed Jul 30, 2004, now U.S. Pat. No. 7,749, 10 persons are of value. These estimates can be obtained through 544, issued Jul. 6, 2010, which is a Continuation of U.S. epidemiologic studies or special Surveys in specific popula patent application Ser. No. 10/241,973, filed Sep. 12, 2002, tions. now abandoned; all of the foregoing applications are incor Issues related to the case definition of AIDS were discussed porated herein by reference in their entireties. by the Conference of State and Territorial Epidemiologists 15 (CSTE) at its annual meeting in Madison, Wis., Jun. 2-5. BACKGROUND OF THE INVENTION 1985. The CSTE approved the following resolutions: 1. that the case definition of AIDS used for national report 1. Field of the Invention ing continue to include only the more severe manifestations This invention relates to a composition for treating AIDS of HTLV-III/LAV infection; and and related conditions, and more particular, to a composition 2. that the Center For Disease Control (CDC) develop more comprising at least one extract of a selected plant. inclusive definitions and classifications of HTLV-III/LAV 2. Description of the Prior Art infection for diagnosis, treatment, and prevention, as well as Patients with illnesses that, in retrospect, were manifesta for epidemiologic Studies and special Surveys; and tions of acquired immunodeficiency syndrome (AIDS) were 3. that the following refinements be adopted in the case first described in the summer of 1981 CDC Pneumocystis 25 definition of AIDS used for national reporting: pneumonia Los Angeles. MMWR 1981, 30:250-2; CDC - a. In the absence of the opportunistic diseases required by Kaposi's sarcoma and Pneumocystis pneumonia among the current case definition, any of the following diseases homosexual men New York City and California. MMWR will be considered indicative of AIDS if the patient has a 1981, 30:305-8. A case definition of AIDS for national positive serologic or virologic test for HTLV-III/LAV: reporting was first published in the MMWR in September 30 1. disseminated histoplasmosis (not confined to lungs or 1982 CDC Hepatitis B virus vaccine safety: report of an lymph nodes), diagnosed by culture, histology, or antigen inter-agency group MMWR 1982, 31:465-67: CDC Up detection; date on acquired immune deficiency syndrome (AIDS)— 2. isosporiasis, causing chronic diarrhea (over 1 month), United States. MMWR 1982, 31:507-14. Since then the diagnosed by histology or stool microscopy; definition has undergone minor revisions in the list of dis 35 3. bronchial or pulmonary candidiasis, diagnosed by eases used as indicators of underlying cellular immunodefi microscopy or by presence of characteristic white plaques ciency Jaffe HW. Bregman DJ, Selik RM. Acquired immune grossly on the bronchial mucosa (not by culture alone); deficiency syndrome in the United States: the first 1,000 4. non-Hodgkins' lymphoma of high-grade pathologic cases. J Infect Dis 1983, 148:339-45; Jaffe HW Selik RM. type (diffuse, undifferentiated) and of B-cell unknown immu Acquired immune deficiency syndrome. is disseminated 40 nologic phenotype, diagnosed by biopsy: aspergillosis predictive of underlying cellular immune defi 5. histologically confirmed Kaposi's sarcoma in patients ciency?, (Reply to letter), J Infect Dis 1984, 149:829; Selik R who are 60 years old or older when diagnosed. M. Haverkos H W. Curran J. W. Acquired immune deficiency b. In the absence of the opportunistic diseases required by syndrome (AIDS) trends in the United States, 1978-1982. Am the current case definition, a histologically confirmed J Med 1984, 76:493-500; CDC, Update: acquired immuno 45 diagnosis of chronic lymphoid interstitial pneumonitis deficiency syndrome (AIDS)—United States. MMWR 1984, in a child (under 13 years of age) will be considered 32:688-91 indicative of AIDS unless test(s) for HTLV-III/LAV are Since the 1982 definition was published, human T-cell negative. lymphotropic virus type III/lymphadenopathy-associated c. Patients who have a lymphoreticular malignancy diag virus (HTLV-III/LAV) has been recognized as the cause of 50 nosed more than 3 months after the diagnosis of an AIDS. The clinical manifestations of (HTLV-III/LAV) infec opportunistic disease used as a marker for AIDS will no tion may be directly attributable to infection with this virus or longer be excluded as AIDS cases. the result of secondary conditions occurring as a consequence d. To increase the specificity of the case definition, patients of immune dysfunction caused by the underlying infection will be excluded as AIDS cases if they have a negative with (HTLV-III/LAV). The range of manifestations may 55 result on testing for serum antibody to HTLV-III/LAV. include none, nonspecific signs and symptoms of illness, have no other type of HTLV-III/LAV test with a positive autoimmune and neurologic disorders, a variety of opportu result, and do not have a low number of T-helper lym nistic infections, and several types of malignancy. AIDS was phocytes or a low ratio of T-helper to T-suppressor lym defined for national reporting before its etiology was known phocytes. In the absence of test results, patients satisfy and has encompassed only certain secondary conditions that 60 ing all other criteria in the definition will continue to be reliably reflected the presence of a sever immune dysfunc included. CDC will immediately adopt the above tion. Current laboratory tests to detect (HTLV-III/LAV) anti amendments to the case definition of AIDS for national body make it possible to include additional serious conditions reporting. in the syndrome, as well as to further improve the specificity This revision in the case definition will result in the reclas of the definition used for reporting cases. 65 sification of less than 1% of cases previously reported to The current case definition of AIDS has provided useful CDC. The number of additional new cases reportable as a data on disease trends, because it is precise, consistently result of the revision is expected to be small. Cases included US 8,771,763 B2 3 4 under the revised definition will be distinguishable from cases logically compromised disease, as well as a variety of AIDS included under the old definition so as to provide a consistent related ailments, including recurrent and persistent fever, basis for interpretation of trends. CDC will also develop draft chronic diarrhea, dermatitis, generalized lymphodenpathy, classifications for disease manifestations of HTLV-III/LAV persistent cough, general pain, tuberculosis, and amenorrhea. infections other than AIDS, distribute these widely for com ment, and publish the results. Reported by Conference of The extract is prepared from the bark, leaf, root and stems of State and Territorial Epidemiologists; AIDS Br., Div of Viral at least one plant from within the apocynaceae, annonaceae, Diseases, Center for Infectious Disease, CDC. dichapetalaceae, annoceae, cynocynaceae, asclepiadaceae, Han et al. Disclosed a process for preparing an extracted combretaceae, amaranthaceae, araceac, cyperaceae, anacar substance from a mixture of a non-fat starch from Ricini diaceae, , bombacaceae, and caricacea plant Semen and a root of Coptis Sp for therapeutic applications of 10 families. AIDS U.S. Pat. No. 5,928,645. The authors maintain that A suitable plant is selected. Preferably a mixture of at least the extracted substance was effective in treating AIDS but two plants is selected. Suitable plants are selected from a provided no clinical data as to the effect of this substance in family of plants including (1) apocynaceae, (2) annonaceae, AIDS patients. In continuing work, Han et al., demonstrated (3) dichapetalaceae, (4) annoceae, (5) cynocynaceac, (6) ascl significantanti-oxidant capacity of their Ricini Semen extract 15 using a chemiluminescence assay Hong, E. K. Kim, Y. K. epiadaceae, (7) combretaceae, (8) amaranthaceae, (9) Lee, W. C., Shin, H. K., and Kim, J. B. Measurement of , (10) cyperaceae, (11) anacardiaceae, (12) bignoni antioxidation activity based on chemiluminescence reaction. aceae, (13) bombacaceac, (14) anarcardiaceae and caricaceae In Bioluminescence and Chemiluminescence (Status plant families. Report), Eds. Szalay, A.A., Kricka, L.J., and Stanley, P. John These plants are tropical herbs that grow naturally and can Wiley & Sons Ltd. London, England, pp. 244-246, 1993. be thus cultivated in tropical, Savanna, grassland or lightly Antioxidant activity of Ricini Semen extract was compared wooded forests of West Africa. These desert plants can also be with t-butylhydroxy toluene (BHT), a potent antioxidant found in other tropical regions of the world, including Asia, known to people of ordinary skill in the field of the invention. Asia Minor, South America, and possibly the South-Western, The authors therefore proposed that Ricini Semen extract has 25 Western and Plains regions of the United States. The active anti-HIV effect although no clinical data was presented. medicaments from these plants include, but are not limited to Investigations of the Ricini Semen extract in laboratory ani glyceryl esters, Saponins and several derivatives of alkaloids, mals by Sub-cutaneous injection revealed significant tubular glycosides, proteins, fats, and Sugars. necrosis, glomerulonephritis, and vacuolation in livers of male and female mice, interstitial nephritis being demon The plants perse are not employed as the requisite medi strated as well in female mice. Rats showed similar symptoms 30 cament, but rather the extract of Such selected plant or plants. in both of the male and female. Mitosis in the liver was The extraction process for the medicaments from the respec typically found, and extramedullary hematopoiesis in the tive plants comprises the following: liver and spleen also were frequently observed. Other organs (a) harvesting the barks, stems, and roots of each were not changed compared to controls U.S. Pat. No. 5,928, plant, and cutting these into chips and chunks; 645. 35 (b) washing and drying the chips and chunks under a con Chen et al., U.S. Pat. No. 6,077,512 disclosed a novel trolled temperature condition, typically about 15° to 68 C. topical treatment method for curing black foot disease using for about 3 days; plant extracts. The extract medicament comprised a basis part (c) proportionally mixing the washed and dried materials consisting of equal amounts of ground, powdered, and mixed from each plant to formulate a mixture needed for each type clove, frankincense, myrrha, fhizama arisaematis, pinellia, 40 of clinical application; monkshood (root) or kusneZoff monkshood (root), and tuber (d) grinding the resultant mixture of plant parts to a powder of bamboo-leaved orchid, and an adjuvant part consisting of composition having a particle size typically ranging in size equal amounts of round, powdered, and mixed borneol, pow from about 100 microns to about 10,000 microns; dered soy bean, borax, Coptis root and/or phellodendron (e) extracting about one part of the resultant powdery mix amureause, and sepia aculeata. The medicine is used in Such 45 ture in about two parts of purified water under slow percola a manner that the powdered basis part is mixed and stirred with tea water until it becomes plaster-like, and the adjuvant tion for about 1 to about 5 hours under a temperature in the part is scattered in dry form onto the wound or Swollen area range of about 76° to about 116°C. and allowing the mixture caused by the black foot disease before the plaster-like basis to cool in appropriate containers under ambient temperature part is applied to the wound or swollen area about 0.5 cm in conditions, i.e., about 16° to about 33°C., for approximately thickness. The wound is then bandaged and the medicine is 50 1 to 2 days; renewed once or twice a day until fresh flesh appears in the (f) re-extracting the resultant mixture in a second percola wound. Thereafter, the medicine is continuously applied but tion process using approximately 2 parts of purified water in a dry form until the wound is completely healed. The under slow percolation for about 1 to about 5 hours under a extract medicament composition taught by Chen et al., does temperature in the range of about 76° to about 116° C. and not have any impact on AIDS itself as a systemic disease. 55 allowing the mixture to cool in appropriate containers under ambient temperature conditions i.e., about 16° to about 33° SUMMARY OF THE INVENTION C., for approximately 1 to 2 days; (g) repeating the extraction process a third time using a The present invention is related to a composition for treat double portion of purified water under slow percolation for ing AIDS and associated conditions related to AIDS. the 60 about 1 to about 5 hours under a temperature in the range of composition comprises a medicament which is an extract of at about 76° to about 116°C. and allowing the mixture to cool in least one plant family. appropriate containers under ambient temperature conditions i.e., about 16° to about 33°C., for approximately 1 to 2 days: DETAILED DESCRIPTION (h) adding a conventional preservative system, e.g., 65 cresols, parabens, p-chlormoetaxylenol, benzoates, alcohols, The present invention relates to a novel extract medicament to maintain antimicrobial preservative efficacy of the mixed for use in treating AIDS, an immune deficiency or immuno plant extract; US 8,771,763 B2 5 6 (i) mixing the extracts in a suitable container, and Subject powder for use as an injectable or Solid product such as a ing the resulting elute repeatedly to filtration under appropri tablet; or by subjecting the resultant product to a filtration ate pressure and temperature conditions, to yield a pure, through a membrane filter and then a lypohilization to give clean, preserved plant extract for human consumption; powders; and then packaging the resulting mixed extracts in () fill the resultant extract through a stainless steel strainer appropriate closure systems for clinical use. into appropriate containers for distribution; and Typically the resultant concentrated extract contains the (k) labeling the containers and presenting these for storage following compounds for each plant concentrate obtained: (The resultant concentrate may also be further concentrated see L. Watson and M. J. Dallwitz (1992) onwards). The into powder under reduced temperature/pressure conditions, Families of Flowering Plants Descriptions, Illustrations, e.g., by tray drying, solvent extraction, solvent exclusion, or 10 Identification, and Information Retrieval. Version: 14 Dec. spray drying, to result in a yellowish-brown amporphous, 2000):

PLANT COMPOUNDS (1) Apocynaceae : Subclass Dicotyledonae; Tenuinucelli. cyanogenics, alkaloids iridoids verbascosides, Dahlgren's Superorder Gentianiflorae. Species proanthocyanidins, cyanidins delphinidins, flavonols, kaempferols, quercetins, elagic acid, Genera 164: Acoikanthera, Adenium; Aganonetion, ursolic acid, saponins sapogenins, aluminum Aganosma; Alafia, Allamanda, Aliomarkgrafia, salts, sucrose, oligosaccharides, and Sugar Allowoodsonia, Alstonia, Alyxia, Anocalyx, alcohols Ambelania, Ansonia, Ancylobotrys, Anechites, Angadenia, Anodendron, Apocyntin; Arduina, Artia, Asketanthera, Aspidosperma, Baissea, Beaumonia, Botisigonia, Cabucaia, Calichia, Calocrater, Cameraria, Carissa, Carpodiiniis, Carruthersia, , Catharanthus, , , Chamaecilitandra, Chilocarpus, Chonemorpha, Cleghornia, Clitandra, Condylocarpon, Colina, Craspidospermin, Crioceras, Cycladenia, Cyclocotyla, Cylindropsis, Delphyodon, Dewevrella, Dictyophleba, Dipladenia, Diplorhynchus, Dyera, Ecdysanthera, Echites, Elytropits, Epigynium, Eucorymbia, Farquharia, Fernaldia, Forsteronia, Funtumia, Galactophora, Geissospermum, Gonioma, Grisseea, Hancornia, Haplophyton, Himatanihtis, Hollarrhena, Hunteria, Hymenolophus, Ichnocarpus, Isonema, Ixodonerium; Kamettia, Kibataia, Kopsia, Lacmeliea, Landolphia, Laubertia, Laxopitimeria, Lepinia, Lepiniopsis, Leticoniotis, Lochnera, Lyonsia, Maconibea, Macropharynx, Macrosiphonia, Malouetia, Mandevilia, Mascarenhasia, Melodinus, Mesechites, Micrechtites, Microplumeria, Molongum, Mortonieia, Motandra, Mucoa, Neobracea, Neocouma, , Nouettea, Ochrosia, Odontadenia, Orthopichonia, Oncinois, , Pachouria, Papuechites, Parahancornia, Parameria, Parepigynum, , Peitastes, Pentalinon, Petchia, Picraima, Plectaneia, Pleiocarpa, Pleioceras, Plumeria, Pottsia, Prestonia, Pycnobotiva, Guiotania, Ratiwolfia, Rhabda denia, Rhazya, Rhigospira, Rhodocalyx, Rhyncodia, Saba, Saipincies, Schizozygia, Secondatia, Sindechites, Spongiosperma, Skytanthus, Spirolobium, Stennadenia, Stephanostegia, Stephanostena, Stipecoma, Sir empeiopsis, Strophanthus, Tabernaemoniana, Tabernanihe, Tennadenia, Thenardia, Thevetia, Tintinnabularia, Tracheiospermum, Urceola, Urnularia, Vahadenia, Vallariopsis, Vallaris, Vallesia, Vinca, Voacanga, , Woytkowskia, Wrightia, Xvinabaria, Xinabariopsis. (2) Annonaceae Taxonomy - Subclass Dicotyledonae; cyanogenics, alkaloids, iridoids, Crassinucelli. Dahlgren's Superorder proanthocyanidins, cyaniding, flavonols, Magnoliiflorae; Annonales. quercetins, elagic acid, Sucrose, Cronquist's Subclass Magnoliidae; Magnoliales. oligosaccharides APG (1998) basal order; Magnoliales. Species 1200. Genera 126; Afoguaiteria, Alphonisea; Ambavia, Anaxagorea, Ancana, Annickia, Annona, Anomianthus, Anonidium, Artabotrys, Asinina, Asteranthe, Balonga; Bocagea, Bocageopsis, Boutiquea, Cananga, Cardiopetalum, Chieniodendron, Cleistochlamys, Cleistopholis, Cremastosperma, US 8,771,763 B2

-continued

PLANT COMPOUNDS Cyathocalyx, CyathoStemma, Cymbiopetailin, DaSociema, Dasymaschalon, Deeringothamnus, Dendrokingstonia, Dennettia, Desmopsis, Desmos, Dicina nona, Dielsiothamnus, Disepaliim, Duckeanthus, Duguetia, Ellipeia, Ellipeiopsis, Enicosanthiim, Ephedranthus, Exelia, Fissistigma, Fitzaiania, Friesodieisia, Froesiodendron, Fusaea, Gilbertiella, Goniothalamus, Greenwayodendron, Gitania, Guatteria, Guaiteriella, Guatteriopsis, HaploStichanthus, Heteropetalum, Hexalobus, Hornschlichia, Isolona, Letestidoxa, Lettowianihtis, Malnea, Mars-popetailin, Meiocarpidium, Meiogyne, Melodorum, Mezzettia, Mezzettiopsis, Miliusa, Mischogyne, Mitrella, Mitrephora, Mikilua, Monanthotaxis, Monocarpia, Monocyclanthus, Monodora, Neostenanthera, Neo-u varia, Oncodostigma, Onychopetalum, Ophrypetailin, Oreomitra, Orophea, Oxandra, Pachypodanthium, Papuaithia, Petalolophus, Phaeanthus, Phoenicanthus, Piptostigma, Platymitra, Polyaithia, Polyatiax, Polyceratocarpus, Popowia, Porcelia, Pseudantabotrys, Pseudephedranthus, Pseudoxandra, Pseudu varia, Pyramidanthe, Raimondia, Reedro insia, Richelia, Roinia, Ruizodendron, Sageraea, Sapranihtis, Scheferomitra, Sphaerocoryne, Steiechocarpits, Stenanona, Tetrameranihtis, Tetrapetailin, Toussaintia, Tridimeris, Trigynaea, Trivalvaria, Unonopsis, Uvaria, Uvariastrum, Uvariodendron, Uvariopsis, Woodiellantha, Xylopia. (3) dichapetalaceae Taxonomy. Subclass Dicotyledonae; Crassinucelli. alkaloids, Saponins, aluminium salts, Dahlgren's Superorder Malviflorae; Euphorbiales, oligosaccharides, Sucrose Cronquist's Subclass Rosidae; Celastrales. APG (1998) Eudicot; core Eudicot; Rosid: Eurosid I; Malpighiales. Species 200. Genera 3: Dichapetailin, Stephanopodium, Tapiira, (Gon-petalum, Falya) (4) Annoceae Schefferomitra Subaequalis, Goniothalamus Alkaloids, cyanidins, flavonols, eg. sesquipedalis kaempferol, quercetin, and myricetin; Saponins sapogenins Sugars as Sucrose; oligosaccharides or Sugar alcohols (5) Cynosuraceae Aegilopaceae, Agrostidaceae, Alopectraceae, alkaloids; arthroquinones, proanthocyanidins, Andropogonaceae; Anomochloaceae, cyanidins, flavonols, kaempferol, quercetin, Anthoxanthaceae, Arundinaceae, Arundineliaceae, myricetin, ellagic acid, aluminium, Sucrose Aspereliaceae, Avenaceae Bambusaceae, and oligosaccharides Chaeturaceae, Chioridaceae, Coieanthaceae Cynosuraceae, Echinariaceae: Ehrhartiaceae, Eragrostidaceae, Festicaceae, Glyceriaceae, Gramineae Hordeaceae, Leptiraceae, Maydaceae, Melicaceae, Miliaceae, Nardaceae, Oryzaceae, Panicaceae, Pappophoraceae, Paspalaceae. Parianaceae, Phaiaridaceae, Pharaceae, Saccharaceae, Spartinaceae, Sporoboiaceae, Stipaceae, Streptochaetaceae, Tristeginaceae, Triticaceae, Zeaceae (6) Asclepiadacea Taxonomy. Subclass Dicotyledonae; Tenuinucelli. alkaloids, hydrocitric-acid, L-carnitine, 3B Dahlgren's Superorder Gentianiflorae; . glucuronides of different acetylated Cronquist's Subclass Asteridae; Gentianales. APG gymnemagenins, gymnemic acid a complex (1998) Eudicot; core Eudicot; Asterid; Euasterid I; mixture of at least 9 closely related acidic Gentianales (as a synonym of Apocynaceae); glucosides, flavonols including kaempferol, Species 2000, Genera 250; Absolmsia, kaempferol and quercetin, aluminium, Sucrose AdeloStemma, Aidomene, Amblyopetailin, and oligosaccharides, iridoids. AmblyStigma, Anatropanthus, , Anisotona, Anomotassa, Arattia; , Aspidoglosslim, Astephantis, Barionia, Belo.Stenna, Bidaria, Biondia, , , Brachystelma, Calotropis, Campestigma, Caraitina, Ceropegia, Cibirhiza, Cioniira, Clemensiella, Cononitra,. Cordylogyne, Corolonema, CosmoStigma, Costantina, US 8,771,763 B2 10 -continued

PLANT COMPOUNDS Cyathostelna, Cynanchiim, Dactylostelna, Dalzielia, Decahedone, Decanema, DeCanemopsis, Dicarpophora; Diplolepis, DiploStigma, Dischidanthus, Dischidia, Ditassa, Dittoceras, Dolichopetalum, Dolichostegia, Dory.Stephania, , DrepanoStemma, Duvalia; Duvaliandra, Echidnopsis, Edithcotea, Enicocarpus, Empilectranthus, Eustegia, Fanninia, Fischeria, Fockea. Foloisia, Frerea, Funastrum, , Glossonema, Glossostelna, Gomphocarpits, Gongronema, Gonioanthelma, GonioStemma, Gonolobus, Graphistenna, Guinnessia, , Gymnemopsis, Harmandiella, Hemipogon, Heterostemma, Heynella, Hickenia, Holostemma, , X-Floodiopsis, Hoya, Hoveila, Huernia, Huerniopsis, Hypolobus, IschnoStemma, Jacaima, Janakia, Jobinia, Kanahia, Karimboiea, Kerbera, Labidostelna, Lagoa, , , , Lhotzkyelia, Lugonia, Ligisma, Macrodiassa; Macropetalum, Macroscepis, Mahafalia, Mahawoa, Manothrix, Margaretta, , Maieiea, Meinia, Meresaidia, Merrillanthus, Metaplexis, Metastelma, Micholitzea, Microdactylon, Microloma, Microstelma, Miraglosslin, Mitostigma, Morrenia, Nationia, Nematostemma, Neoschumannia, , , Odontanthera, Odontostelma, Oncinema, Oncostemma, Ophionella, , Orbeanthus, Orbeopsis, Oreosparte, Orthanthera, Orthosia, , Pachycarpus, Pachycymbium, Papuastelma, Parapodium, Pectinaria, Pentalbothra, Pentacyphus, , Pentasachme, Pentastelma, , Peplonia, Pengularia, Periglossum, Petaliostelma, Petopentia, Pherotrichis, , Platykeleba, Pleurostelma, Podandra, Podostelma, Prosopostelma, Pseudolithos, Ptycanthera, Pycnoneurum, Pycnorhachis, Quaqua, Putist imbingia, Raphistemma, , Rhynchostigma, Rhyssolobium, Rhyssostelma, Rhytidocation, Riocretixia, Rojasia, , , Schistogyne, Schistonema, Schizoglossum, Schubertia, Scyphostelna, Secanone, Seca monopsis, Seshagiria, Sisyranthus, SolenoStemma, Sphaerocodon, Spireila, Siapelia, Stapeiianthus, Siapeiopsis, Stathmostelna, SteleoStemma, Steinagoniin, Stelmatocodon, Stenomeria, Stenostelna, Stigmatorhynchus, Strohopetalum, Stickertia, Swynnertonia, Tassadia, Tavaresia, Telminostelna, Teiosma, Tenaris, Tetractistelna, Tetraphysa, Thozetia, , Treutiera, Trichocation, Trichosacne, Trichosandra, Tridentea, Tromotriche, Tweedia, , Tvlophoropsis, Vaiia, Vincetoxicopsis, , Voharanga, Vohemaria, White Sloanea, Widgrenia, Woodia, (7) Combretaceae Taxonomy. Subclass Dicotyledonae; Crassinucelli. alkaloids, arthroquinones, proanthocyanidins, Dahlgren's Superorder Myrtiflorae; . cyanidins, flavonols, kaempferol; quercetin, Cronquist's Subclass Rosidae; Myrtales. APG myricetin, ellagic acid, aluminium, Sucrose (1998) Eudicot; core Eudicot; Rosid: Eurosid II; and oligosaccharides Myrtales. Species 600. Genera about 20: Anogeissus, Bitchenavia, Buicida, Calopyxis, Calycopteris, Combrettin, , Danisiea, Guiera, Laguncularia, Limnitzera, Macropteranthes, Meiostenon, Pteleopsis, Putisqualis, Strephonema, , Terminaiopsis, Thiloa (8) Amaranthaceae Taxonomy. Subclass Dicotyledonae; Crassinucelli. Cyanogenics, alkaloids, flavonols, quercetin, Dahlgren's Superorder Caryophylliflorae; elagic acid, betalains, saponins, Sapogenins, . Cronquist's Subclass oxalates Caryophyllidae: Caryophyllales. APG (1998) Eudicot; core Eudicot; neither Rosid nor Asterid: Caryophyllales. Species 850. Genera 74: Achyranthes, Achyropsis, Aerva, Allmania, Alternanthera, Amaranthus, Arthraeria, Bittaparon, US 8,771,763 B2 11 12 -continued

PLANT COMPOUNDS Bosea, Bravitlinea, Caicorena, Celosia, Centenna, Centenopsis, Centrostachys, Chamissoa, Charpentiera, Chionothrix., Cyathitia, Dasysphaera, Dasysphaera, Deeringia, Digera, Eriostylos, Froeiichia, Gomphrena, Gossypianthus, Guilleminea, Hebanthe, Hemichroa (-Chenopodiaceae), Henonia, Herbstia, Hermbstaedtia, Indobanaia, Ireneia, Iresine, Kyphocarpa, Lagrezia, Leticosphaera, Lithophila, Lopriorea, Marcelliopsis, Machowia, Neisia, Neocentenna, Nothosaerva, Nototrichium, Nyssanthes, Pandiaka, Pfafia, Philoxerus, Pleuropetalum, Pleuropterantha, Polyrhabda, Pseudogomphrena, Pseudoplantago, Pseudosericocoma, Psilotrichopsis: Psilotrichum: Ptiloitis, Pupaia, Guaternelia, Rosifax, Saitia, Sericocona, Sericocomopsis, Serico rena, Sericostachys, Siamosia, Stilbanthus, Tidestronia, Trichuriella, Volkensinia, Woehleria, Xerosipho (9) Araceae Taxonomy. Subclass Monocotyledonae. Cyanogenics, cynogenic constituents Superorder Ariflorae; Arales. APG (1998) tyrosine-derived, alkaloids, Monocot; non-commelinoid; . Species proanthocyanidins, cyanidin, flavonols, 2000; Genera 106; Agiaodorum, Agiaonema, Kaempferol, quercetin, and quercetin Alloschemone, Aiocasia, Ambrosina, Amorphophalius, Amydrium, Anadendrain, Anaphyllopsis, Anaphyllum, Anchomanes, Anthlirium, Antibias, Aridarum, Ariopsis, Arisaena, Arisarum, Arophyton, Arum, Asterostigma, Biartin, Bognera, Bucephalandra, Caladium, Calia, Callopsis, Carlephyton, Cercestis, Chlorospatha, Coiletogyne, Colocasia, Cryptocoryne, Cuicasia, Cyrtosperma, Diefenbachia, Dracontioides, Draconium, Dractinctiitis, Eminium, Epiprennium, Filarim, Fairtodoa, Gearin, Gonatanihats, Gonatopus, Gorgonidium, Gymnostachys, Hapaline, Helicodiceros, Heteroanidarum, Heteropsis, Holochlamys, Homalomena, Hottarum, Jasarum, Lagenandra, Lasia, Lasimorpha, Lysichiton, Mangonia, Monstera, Montrichardia; Nephthyitis, Orontium, Pediceiiarum, Peitandra, Philodendron, Phymatarum, Pinelia, Piptospatha, Pistia, Podolasia, Pothoidium, Pothos, Protarum, Pseudodracontium, Pseudohydrosme, Pycnospatha, Remusatia, Raphidophora, Rhodospatha, Satiromatum, Scaphispatha, Schismatoglottis, , Spaihanthetin, Spathicarpa, Spathiphyllum, Stenospermation, Stetidinera, Stylochaeton, Sympiocarpus, Synandrospadix, Syngonium, Taccartin, Theriophoniin, Tiphonium, Typhonodorum, , Urospatha, Urospatheila, Xanthosoma, Zamiculcas, Zantedeschia, Zomicarpa, Zomicarpella (10) Cyperaceae Taxonomy. Subclass Monocotyledonae. Alkaloids, proanthocyanidins, cyanidins, Superorder Commeliniflorae: Cyperales. APG delphinidins, flavonols, quercetins, (1998) Monocot; Commelinoid group: Poales. aluminium Species about 5000. Genera about 120; Abildgaardia; Acritius, ActinoSchoentis, Afrotrilepis, Ainitia, Androtrichlin, Anosportin, Arthrostylis, Ascolepis, Ascopholis, Baeothryon, Baumea, Becquerelia, Bisboeckelera, Blysmopsis, Blysmits, Bolboschoentis, Bulbostylis, Calyptrocarya, Capitularina, Carex, Carpha, Calistis, Cephalocarpus, Chorizandra, Chrysitrix, Cladium, Coleochloa, Costularia Courtoisina, Crosslandia, Cyathochaeta, Cyathocona, Cynophyllius, Cypertis, DesmoSchoenus, Didymiandrum; Dipiacrum, Diplasia, Dulichium, Egieria, Eleocharis, Eleogiton, Epischoenus, Eriophoropsis, Eriophortin, Erioscirpus, Evandra, Everardia, Exocarya, Exochogyne, Ficinia, Fimbristylis, Fuirena, Gahnia, Gymnoschoenus, Hellmuthia, Hemicarpha, Hymenochaeta, Hypolytrain, Isolepis, Kobresia, Kyllinga, Kyllingieia, Lagenocarpus, Lepidosperma, Lepironia, Lipocarpha, LophoSchoentis, Machaerina, US 8,771,763 B2 13 14 -continued

PLANT COMPOUNDS Mapania, Mapaniopsi, Mariscus, Mesomelaena, Microdracoides, Micropapyrus, Monandrits, Moreiotia, Neesenbeckia, Nemum, Neimesia, Oreobolopsis, Oreobolus, Oxycarvin, Paramapania, Phylloscirpus, Pleurostachys, Principlina, Pseudoschoenus, Ptilanthelium, Pycreus, Queenslandiella, Reedia, Remirea, Rhynchocladium, Rhynchospora, Rikiella, Schoenopiectus, Schoenoxiphium, Schoenoides, Schoenus, Scirpodendron, Scirpoides, Scirpus, Scleria, Sphaerocypertis, Sumatroscirpus, Syntrinema, Tetraria, Tetrariopsis, Thoracostachyum, Torulinium, Trachystylis, Trianoptiles, Trichoschoenus, Tricostularia, Triepis, Tiviocarya, Uncinia, Vesicarex, Voikielia, Websteria. (11) Anacardiaceae Taxonomy. Subclass Dicotyledonae; Crassinucelli. Alkaloids, iridoids, proanthocyanidins, Dahlgren's Superorder Rutiflorae:. delphinidins, cyanidins, flavonols, eg. Cronquist's Subclass Rosidae: Sapindales. APG kaempferol, quercetin, and myricetin; (1998) Eudicot; core Eudicot; Rosid: Eurosid II; Saponins sapogenins Sugars as Sucrose, Sapindales, Species 600. Genera about 70; oligosaccharides or Sugar alcohols Actinocheita, Anacardium, Androtium, Antrocaryon, Apteroikarpos, Astronium, Baronia, Bonetiella, Boulea, Buchanania, Campnosperma, Cardenasiodendron, Choerospondias, Conocladia, Coint is, Cyrtocarpa, Dracontoneion, Drimycarpus, Ebandolia, Euleria, Euroschiniis, Faguetia, Fegimanra, Giulia, Haematostaphis, Hapiorhiis, Harpephyllum, Heeria, Holigarna, Koordersiodendron, Lannea, Lautrophyllius, Lithrea, Loxopterigium, Loxostylis, Mangifera, Mauria, Melanochyla, Metopium, Micronychia, Montagueia, Mosquitoxviiim, Nothopegia, Ochoter enaea, Operculicarya, Ozoroa, Pachycormus, Parishia, Pegia, Pentaspadon, Pleiogynium, Potipartia, Protorhus, Pseudoprotorhus, Pseudosmodingium, Pseudospondias, Rhodosphaera, Rhus, Schinopsis, Schinus, Sclerocarya, Senecarpus, Snodingium, Solenocarpus, Sorindeia, Spondias, Swintonia, Tapirira, Thyrsodium, Toxicodendron, Trichoscypha. (12) Bignoniaceae Taxonomy. Subclass Dicotyledonae; Tenuinucelli. Alkaloids, iridoids arthroquinones, shikimic Dahlgren's Superorder Lamiiflorae; acid, verbascosides, cornosides, flavonols, Scrophulariales. Cronquist's Subclass Asteridae; quercetins, ursolic acid, Saponins, Sapogenins Scrophulariales. APG (1998) Eudicot; core oligosaccharides, Sucrose, Sugar Eudicot; Asterid; Euasterid I; . Species 650. Genera 110; Adenocalymna, Amphilophium, Amphitecna, Anemopaegna, Argylia, Arrabidaea, Astianihtis, Barnettia, , Calichlamys, Campsidium, , Catalpa, Catophracies, Ceratophytum, Chilopsis, Clytostoma, Collea, Crescentia, Cispidaria, Cybistax, Deiostoma, Depianchea, Digomphia, Dinkiageodoxa, Disticteila, Disticiis, Doichandra, Doichandrone, Eccremocarpus, Ekmanianthe, Fernandoa, Fridericia, Gardnerodoxa, Giaziova, Godmania, Haplolophium, Haplophragma, , Hieris, Incarvillea, Jacaranda, Kigelia, Lamiodendron, Leucocaianiha, Lundia, Macfadyena, Macranthisiphon, Manaosella, Mansoa, Markhamia, Martinella, Melloa, Memora, Millingtonia, Mussatia, Neoiobertia, Neosepicaea, Newboltidia, Nyctoaios, Ophiocoiea, Oroxylum, Paianelia, , Parabiognonia, Paragonia, Paratecoma, Parmentiera, Pauldopia; Perianthomega, Periarrabidaea, Perichlaena, Phryganocydia, Phyllarthron, Phyloctenium, Piriadacus, Pithecoctenium, Pieionotona, Podranea, Potamoganos, Pseudocatalpa, Pyrostegia, Radermachera, Rhigozum, Rhodocoiea, Roentgenia, Romeroa, Saritaea, Sparatiosperma, Spathicalyx, Spathodea, Sphingiphila, Spirotecoma, Stereospermain, Stizophyllum, Tabebuia, Tanaecium, , Tecomanihe, Tecomeia, Tourrettia, Tynanthus, Urbanolophium, Xylophragma, Zeyheria. US 8,771,763 B2 15 16 -continued

PLANT COMPOUNDS For discussion of classificatory problems posed by Scrophtiariaceae, impinging on Bignoniaceae, Biddleiaceae, Caliirichaceae, Plantaginaceae, Hippiiridaceae, Lentibulariaceae, and Hydrostachydaceae, and Such problem genera as Paulownia and Schlegelia, see Olmstead and Reeves (1995). (13) Bombacaceae Taxonomy. Subclass Dicotyledonae; Crassinucelli. Alkaloids, proanthocyanidins, cyanidins, Dahlgren's Superorder Malviflorae: . flavonols e.g. kaempferol and quercetin; Cronquist's Subclass Dilleniidae: Malvales. APG SUCOSE (1998) Eudicot; core Eudicot; Rosid: Eurosid II; Malvales. Species 180. Genera 30; Adansonia, Aguiaria, Bernoulia, Bombacopsis, Bombax, Catostemma, Cavaniilesia, Ceiba, Chorisia, Coeliostegia, Cullenia, Diirio, Eriotheca, Gyranthera, Huberodendron, Kostermansia, Matisia, Neesia, Neobuchia, Ochroma, Pachira, Patinoa, Phragmotheca, Pseudobombax, Quararibea, Rhodognaphaion, Rhodagnaphalopsis, Scleronema, Sepiotheca, Spirotheca, , Bombacaceae, Sterculiaceae and Tiliaceae (14) Anacardiaceae Taxonomy. Subclass Dicotyledonae; Crassinucelli. Alkaloids, arthroquinones, proanthocyanidins, Dahlgren's Superorder Rutiflorae: Sapindales. delphinidin; cyanidin, flavonols, kaempferol, Cronquist's Subclass Rosidae: Sapindales. APG quercetin, myricetin, elagic acid, Saponins, (1998) Eudicot; core Eudicot; Rosid: Eurosid II; Sapogenins, Sucrose, oligosaccharides, Sugar Sapindales. Species 600. Genera about 70; alcohols Actinocheita, Anacardium, Androtium, Antrocaryon, Apteroikarpos, Astronium, Baronia, Bonetiella, Boulea, Buchanania, Campnosperma, Cardenasiodendron, Choerospondias, Conocladia, Cotinus, Cyrtocarpa, Draconiomedon, Drimycarpus, Ebandolia, Euleria, Euroschiniis, Faguetia, Fegimanra, Giulia, Haematostaphis, Hapiorhiis, Harpephyllum, Heeria, Holigarna, Koordersiodendron, Lannea, Lautrophyllius, Lithrea, Loxopterigium, Loxostylis, Mangifera, Mauria, Melanochyla, Metopium, Micronychia, Montagueia, Mosquitoxviiim, Nothopegia, Ochoter enaea, Operculicarya, Ozoroa, Pachycormus, Parishia, Pegia, Pentaspadon, Pleiogynium, Potipartia, Protorhus, Pseudoprotorhus, Pseudosmodingium, Pseudospondias, Rhodosphaera, Rhus, Schinopsis, Schinus, Sclerocarya, Senecarpus, Sorindeia Snodingium, Solenocarpus, Spondias, Swintonia, Tapirira, Thyrsodium, Toxicodendron, Trichoscypha. (15) Caricaceae Taxonomy. Subclass Dicotyledonae; Crassinucelli. mustard-oils, alkaloids, Saponins sapogenins Dahlgren's Superorder Violiflorae; Violales. Cronquist's Subclass Dilleniidae; Violales. APG (1998) Eudicot; core Eudicot; Rosid: Eurosid II; . Species 55. Genera 4: Carica, Cylicomorpha, , .

Prior to the administration to a patient an extract or a varies according to factors such as the potency of the ex mixture of extracts are typically diluted by combination with tract(s) the route of administration of the formulation, and the a pharmecologically compatible solvent, e.g., ethanol or ss mechanical system used to administer the formulation. A water to produce atherapeutic Solution. Typically the amount therapeutically effective amount of a particular extract or or concentration of the extract or mixed extracts in the thera mixture of extracts can be selected by those of ordinary skill peutic solution ranges from 0.0001 to 10.0 weight percent of in the art with due consideration of such factors. Generally a the total weight of the solution. Of course, the extract or therapeutically effective amount will be from about 0.005 mixture of extracts is present in a therapeutically effective 60 parts weight to about 2 parts by weight based on 100 parts by amount, that is, an amount Such that the extract or mixture of weight of the therapeutic Solution, or if in Solid form, e.g., extracts can be administered in a therapeutically effective tablet or capsule, 0.001 to 10 parts by weight of the weight of amount through conventional oral, nasal, aerosol, topical, the tablet or capsule. intravenous, peritoneal, etc. means. For oral administration, either solid or fluid unit dosage The term “amount’ as used herein refers to a quantity or to 65 forms can be prepared. For preparing solid compositions such a concentration, as appropriate to the context. The amount of as tablets, the extract or extract mixture is mixed into formu extract(s) that constitutes a therapeutically effective amount lations with conventional ingredients, such as talc, magne US 8,771,763 B2 17 18 sium Stearate, dicalcium phosphate, magnesium aluminum The term “unit dosage form” refers to physically discrete silicate, calcium sulfate, starch, lactose, acacia, methylcellu units suitable as unitary dosages for human Subjects and ose, and functionally similar materials as pharmaceutical animals, each unit containing a predetermined quantity of diluents or carriers. Capsules are prepared by mixing the active material calculated to produce the desired pharmaceu tical effect in association with the required pharmaceutical extractor extract mixture with an inert pharmaceutical diluent diluent, carrier or vehicle. The specifications for the unit and filling the mixture into a hard gelatin capsule of appro dosage forms of this invention are dictated by and dependent priate size. Soft gelatin capsules are prepared by machine on (a) the unique characteristics of the active material and the encapsulation of a slurry of the extract or extract mixture with particular effect to be achieved and (b) the limitations inher an acceptable vegetable oil, light liquid petrolatum or other ent in the art of compounding Such an active material for use inert oil. 10 in humans and animals. Fluid unit dosage forms for oral administration Such as Examples of unit dosage forms are tablets, capsules, pills, syrups, elixirs and Suspensions can be prepared. The water powderpackets, wafers, suppositories, granules, cachets, tea soluble forms can be dissolved in an aqueous vehicle together spoonfuls, dropperfuls, ampoules, vials, aerosols with with Sugar, aromatic flavoring agents and preservatives to metered discharges, segregated multiples of any of the fore 15 going, and other forms as herein described. form a syrup. An elixir is prepared by using a hydroalcoholic Thus, a formulation of the invention includes a therapeutic (e.g., ethanol) vehicle with Suitable Sweeteners such as Sugar extract(s) which may beformulated with conventional, phar and saccharin, together with an aromatic flavoring agent. maceutically acceptable, vehicles for topical, oral or Suspensions can be prepared with an aqueous vehicle with the parenteral administration. Formulations may also include aid of a suspending agent Such as acacia, tragacanth, methyl Small amounts of adjuvants such as buffers and preservatives cellulose and the like. to maintain isotonicity, physiological and pH stability. Means Appropriate formulations for parenteral use are apparent to of preparation, formulation and administration are known to the practitioner of ordinary skill. Usually, the therapeutic those of skill. See generally Remington's Pharmaceutical extract or extract mixture is prepared in aqueous solution in a Science 15' ed., Mack Publishing Co., Easton, Pa. (1980). concentration of from about 1 to about 100 mg/ml. More 25 Slow or extended-release delivery systems, including any typically, the concentration is from about 10 to about 20 of a number of biopolymers (biological-based systems), sys mg/ml. The formulation, which is sterile, is suitable for vari tems employing liposomes, and polymeric delivery systems, ous parenteral routes including intra-dermal, intraarticular, can be utilized with the extracts described herein to provide a intra-muscular, intravascular, and Subcutaneous. continuous or longterm source of therapeutic compound. In addition to the therapeutic extract or extract mixture the 30 Such slow release systems are applicable to formulations for compositions may include, depending on the formulation topical, ophthalmic, oral, and parenteral use. desired, pharmaceutically-acceptable, non-toxic carriers or Delivery of the inventive therapeutic extractor extract mix diluents, which include vehicles commonly used to form ture is usually by oral administration as a solution. However, pharmaceutical compositions for animal or human adminis where necessary, therapy, e.g., intra-dermal, intra-articular, tration. The diluent is selected so as not to unduly affect the 35 intramusular or intravenous, is also employed biological activity of the combination. Examples of such As previously indicated, the resultant medicament extract diluents which are especially useful for injectable formula e.g., from a single plant or a mixture of any of the afore tions are water, the various Saline solutions, Ringer's Solu mentioned plants, has been found to be effective in treating tion, dextrose solution, and Hank's Solution. In addition, the AIDS but also in treating associated conditions related to pharmaceutical composition or formulation may include 40 AIDS. Such associated conditions include recurrent and per additives such as other carriers; adjuvants; or nontoxic, non sistent fever, chronic diarrhea, dermatitis, generalized lym therapeutic, nonimmunogenic stabilizers and the like. phodenpathy, persistent cough, general pain, tuberculosis, Furthermore, excipients can be included in the formula and amenorrhea. tion. Examples include cosolvents, Surfactants, oils, humec tants, emollients, preservatives, stabilizers and antioxidants. 45 EXAMPLES Any pharmacologically acceptable buffer may be used, e.g., tris orphosphate buffers. Effective amounts of diluents, addi 1. About 105 patients suffering from AIDS were treated tives and excipients are those amounts which are effective to with mixtures of plant extracts, obtained as above described obtain a pharmaceutically acceptable formulation in terms of as approximately 10% weight percent therapeutic Solutions solubility, biological activity, etc. with the following results as reported in TABLE II, below. TABLE II

Combinations of Plant Extract Medicaments for Treatment of AIDS Related Ailments

Stage of AIDS Disease Typical Symptoms Mixture of Plant Extract Used

Stage 1: Critically ill - non Significant weight loss Apocynaceae (17 weight percent) ambulatory patients - Frequent and recurrent Fever Annonaceae (10 weight percent) 3-6 months duration of Chronic Diarrhea Dichapetalaceae (14 weight percent) treatinent Dermatitis Annoceae (17 weight percent) (Complete 90 to 98%) Generalized Lymphodenpathy, Cynocynaceae (21 weight percent) Cough Asclepiadaceae (14 weight percent) General Pain Combretaceae (7 weight percent) US 8,771,763 B2 19 20 TABLE II-continued

Combinations of Plant ExtractMedicaments for Treatment of AIDS Related Ailments Stage of AIDS Disease Typical Symptoms Mixture of Plant Extract Used Pneumonia Diluted with Kaposi's sarcoma to give a 0.5 to 25 weight Herpes Zoster percent extracts solution Tuberculosis Amenorrhea Stage 2: Moderately ill - after going Lack of appetite Apoocynaceae (15 weigh percent) through stage 1 treatment program Immune dysfunction Amaranthaceae (17 weight percent) 3-6 months duration of treatment Aroceae (17 weight percent) (Complete 95%) Cyperaceae (17 weight percent) Anacardiaceae (17 weigh percent) bignoniaceae (17 weigh percent) Diluted with water to give a 0.5 to 25% weight percent extract solution Stage 3: Relatively ill Restoration of immune protection Anoceae (17 weight percent) but ambulatory with good vitals Anarcadiaceae (20 weigh percent) after stage 2 program Aroceae (20 weight percent) 3-6 months duration of treatment Bombacaceae (20 weight percent) Caricaceae (17 weight percent) Combretaceae (6 weight percent) Diluted with water to give a 0.5 to 2.5 weight percent extract so ution ORAL DOSAGES: Adults 3 tablespoonsfull 3 times daily Pediatric: 2 teaspoonful 3 times daily

II. Treatment of HIV Patients for AIDS Related Ailments 30 We claim: 1. A composition for use in treating symptoms of AIDS A total of 300 patients presenting moderate to advanced patients, comprising a mixture of aqueous extracts from the stages of AIDS, particularly with respect to debilitating ail following plants: ments, including persistent fever, chronic diarrhea, dermati (a) Pleiocarpa bicarpellata, Alstonia boomei, or a mixture tis, generalized lymphodenapathy, persistent cough, general 35 thereof; pain, tuberculosis and amenorrhea, were treated with an (b) Alternanthera pungens, extract mixture solution of the invention. The mixture com (c) Anchomanes diformis, prised Anoceae (10 to 20 weight percent), Anarcadiaceae (d) Scleria boivinii; (15-20 weight percent), Araceae (15 to 20 weight percent) (e) Lannea acida, ; Spondias Bombacaceae (20 weight percent), Caricaceae (15 to 20 40 mombin, or a mixture thereof, and weight percent), and Combretaceae (3 to 10 weight percent). (f) Kigelia africana, The mixture was then diluted with water to give about 10 wherein the symptoms are one or both of lack of appetite weight percent extract solution. The Solution was adminis and immune dysfunction. tered to each patient at a dose of 3 tablespoons three times per 2. The composition according to claim 1, wherein day. (a) Pleiocarpa bicarpellata, Alstonia boomei, or a mixture 45 thereof is present in the composition in an amount of 15 All treated patients in this group of studies had none of the weight percent; debilitating symptoms in the time periods indicated in (b) Alternantherapungens is present in the composition in TABLE III, below: an amount of 17 weight percent; (c) Anchomanes diformis is present in the composition in TABLE III 50 an amount of 17 weight percent; (d) Scleria boivinii is present in the composition in an Symptom Approximate Recovery Time (Average) amount of 17 weight percent; RPFever 1 Week (e) Lannea acida, Antrocaryon micraster; Spondias Chronic Diarrhea 1 Week mombin, or a mixture thereof is present in the composi Dermatitis 3 Weeks 55 Generalized Lymphodenpathy 4Weeks tion in an amount of 17 weight percent; and Cough 2 Weeks (f) Kigelia africana is present in the composition in an General Pain 4Weeks amount of 17 weight percent, Tuberculosis 12 Weeks wherein the mixture of extracts is further diluted with water Amenorrhea 1 Week to give a 0.5 to 25 weight percent extracts solution. k k k k k