US 2008O166435A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0166435 A1 Pylypchuk (43) Pub. Date: Jul. 10, 2008

(54) COMPOSITION AND METHODS OF USE OF Publication Classification AN IMMUNOMODULATOR (51) Int. Cl. A636/00 (2006.01) A636/53 (2006.01) (76) Inventor: Volodymyr Pylypchuk, Kiev (UA) A6IR 36/484 (2006.01) A636/886 (2006.01) A6IR 36/68 (2006.01) A6IP3L/00 (2006.01) Correspondence Address: A6IPL/I6 (2006.01) CONNOLLY BOVE LODGE & HUTZ, LLP A6IP 29/00 (2006.01) 1875 EYE STREET, N.W., SUITE 1100 A6IP37/00 (2006.01) A6IR 36/28 (2006.01) WASHINGTON, DC 20036 A636/73 (2006.01) A6IR 36/38 (2006.01) (52) U.S. Cl...... 424/730; 424/745; 424/725; 424/757; (21) Appl. No.: 11/965,377 424/765; 424/744; 424/737; 424/764; 424/738 (57) ABSTRACT (22) Filed: Dec. 27, 2007 A composition including one or more of elecampane rhizome (Inula sp.), fennel fruit (Foeniculum sp.), juniperberry (Juni perus sp.), licorice root (Glycyrrhiza sp.), oregano herb (Oreganum sp.), marigold flowers (Calendula sp.), rose hips Related U.S. Application Data (Rosa sp.), and thyme (Thymus sp.), or an extract thereof. The composition is useful for treating infectious diseases, for (60) Provisional application No. 60/877,631, filed on Dec. example viral and microbial infections, and for reducing the 29, 2006. toxic effects of chemotherapeutic agents.

EgAm A relative values S. Arm A absolute values 2 Arm B relative values SAm Babsolute values Patent Application Publication Jul. 10, 2008 US 2008/O166435 A1

Fig. 1.

|TT:LL,º |

gAm A relative values E. Arm A absolute values 2 Arm B relative values S. Arm Babsolute Values

US 2008/0166435 A1 Jul. 10, 2008

COMPOSITION AND METHODS OF USE OF 0009. In another aspect, the inventors have found a method AN IMMUNOMODULATOR of treating a subject having an infectious disease comprising administering a composition comprising at least one plant CROSS REFERENCE TO RELATED material selected from the group consisting of Inula sp., Foe APPLICATIONS niculum sp., Juniperus sp., Glycyrrhiza sp., Oreganum sp., Calendula sp., Rosa sp., and Thymus sp., or an extract thereof, 0001. This application claims the benefit of U.S. Provi or a combination of the extracts, whereby liver function or sional Application No. 60/877,631, filedon Dec. 29, 2006, for incidence of adverse events is improved. all purposes. The entirety of this application is hereby incor 0010. In yet another aspect, the inventors have found a porated by reference. method of ameliorating adverse effects of chemotherapy in a Subject in need thereof comprising administering a composi FIELD OF THE INVENTION tion comprising plant material comprising Inula sp., Foenicu 0002 The invention regards medicinal herb compositions lum sp., Juniperus sp., Glycyrrhiza sp., Oreganum sp., Cal and their use in patient treatment. endula sp., Rosa sp., or Thymus sp., or a combination thereof, or extracts thereof or a combination of extracts thereof. BACKGROUND OF THE DISCLOSURE 0011. In another aspect, the invention is a method of treat ing disease, including infectious viral disease. 0003 Antiretroviral drug resistance, drug toxicity, and 0012 We evaluated the clinical benefit of the composition adherence are major concerns in the clinical management of No. 1 of the present invention in comparison to standard ART HIV infection. On the other hand, the immune activation in a multicenter trial conducted at four regional hospitals in caused by immune reaction to HIV, is now recognized as a Ukraine. Here we present data from a 32-week, open label, major cause of depletion of CD4" (CD4) T-cells and resulting three-arm trial in 70 HIV-infected individuals who were immunodeficiency. In fact, African monkeys, the natural treated either with zidovudine (AZT), lamividine (3TC), and hosts of simian immunodeficiency virus have adapted to this efavirenz (EFV), or with AZT/3TC/EFV in combination with retrovirus by blocking immune activation and thus remaining the composition of the present invention, or the composition healthy. An optimal therapeutic solution would be an effec of present invention alone, assigned to arms A, B, and C. tive and safe immunotherapy that could regulate the immune respectively. response in a manner favorable to a host. 0004 Dzherelo is an oral immunomodulating agent pro 0013 Data on treatment of patients suffering from tuber duced from 26 plant materials by the inventor. It contains culosis is also presented separately. concentrated extracts from medicinal plants. In vitro studies 0014. An immunomodulating agent has been evaluated in on cultured thymocytes and epithelial thymic cells have 70 HIV-infected individuals who were divided into three shown that Dzherelo can induce synthesis of serum thymic treatment arms: the first arm, serving as a control, received factor and other substances with thymus like activity. Experi standard antiretroviral therapy (ART), that is, zidovudine/ ments on laboratory animals demonstrated the restoration of lamividine/efavirenz (AZT/3TC/EFV); second, AZT/3TC/ endocrine function and increase of thymus weight after par EFV plus the composition of the present invention; and third, tial thymectomia. It has been Successfully used in the past for the composition of present invention alone which was given the therapy of various infectious diseases of viral origin Such orally, twice daily. During 32 weeks of follow-up CD4 cell as herpes and Epstein-Barr viruses. Prior evidence indicates counts increased progressively in all arms, reaching + 102. the tendency of Dzherelo to restore suppressed immunity +190, and +175 cells/mm, in arms A, B, and C, respectively. characteristic of chronic bacterial infections and malignant The proportion of patients who experienced adverse events diseases. Furthermore, Dzherelo has shown efficacy in treat attributable to study medication was 65%, 24%, and 5% in ment of autoimmune diseases. arms A, B, and C, respectively. The composition of the 0005 Pilot trials conducted by us in HIV-infected indi present invention appears to attenuate hepatic toxicity in viduals have shown that Dzherelo is safe, can increase the patients receiving ART as determined by liver function test. total and CD4 lymphocyte counts, and reduce the incidence Mean baseline values for ALT aminotransferase were 36, 62 of opportunistic infections. In addition it appeared to have a and 72 U/L in arms A, B, and C, respectively. At study favorable effect in diminishing the toxicity of antiretroviral conclusion, ALT values had risen to a mean 78 U/L in arm A drugs. but declined to 38 and 31 U/L in arms B and C, respectively. The composition of the present invention was also useful in 0006 Dzherelo is a complex mixture, however. An effec correcting AIDS-associated wasting. The average weight tive composition having fewer components would be desir gain was 1.4., 6.9, and 5.1 kg for arms A, B, and C. These able. clinical data indicate that the composition of present inven SUMMARY OF THE DISCLOSURE tion is very safe and has beneficial clinical effect in the treat ment of HIV and AIDS. 0007 We now present a simplified herbal composition 0015. Another embodiment of the invention comprises a prepared from essentially eight plant materials or extracts Somewhat more complex combination of plant materials use thereof. Surprisingly, this simpler version, termed composi ful, e.g., for treatment of tuberculosis patients. This embodi tion No. 1, had an equal effect as one that contained a higher ment is termed composition No. 2. number of herbs. 0016. The complex combination (“No. 2) of herbal mate 0008. In one aspect the inventors have identified a useful rials has Superior efficacy for Some illnesses than when said composition consisting essentially of plant material from materials are used alone. Such a combination can have fol Inula sp., Foeniculum sp., Juniperus sp., Glycyrrhiza sp., lowing ingredients, which can be administered together or as Oreganum sp., Calendula sp., Rosa sp., and Thymus sp., oran three sets of ingredients. The first set (Composition No. 2 set extract thereof, or a combination of the extracts. No. 1) will essentially contain medicinal plants such as Aloe US 2008/0166435 A1 Jul. 10, 2008

(Aloe arborescens), Common knotgrass (Polygonum avicu garticks (Bidens tripartite), Sage (Salvia officinalis), Dog lare), Yarrow (Achillea millefolium), Purple coneflower rose (Rosa canina), and Juniper berries (Juniperus commu (Echinacea purpurea), St. John's Wort (Hypericum perfora nis). Composition No. 3 can be combined with Composition tum), Centaury (Centaurium erythraea), Snowball tree ber No. 2, set 2 and/or set 3. ries (Viburnum opulus), Nettle (Urtica dioica), Dandelion (Taraxacum officinale), Sweet-sedge (Acorus Calamus), 0022. Another embodiment (termed composition No. 4) Oregano (Oreganum majorana), Marigold (Calendula offici relates to compositions that include, as a first component, the nalis), Seabuckthornberries (Hippophae rhamnoides), Ele active ingredient from Aloe and as a second component at campane (Inula helenium), Tormentil (Potentilla erecta), least one active ingredient isolated from the group of medici Greater plantain (Plantago major), Wormwood (Artemisia nal plants: Common knotgrass (Polygonum aviculare), Yar sp.), Siberian golden root (Rhodiola rosea), Cudweed row (Achillea millefolium), Purple coneflower (Echinacea (Gnaphalium uliginosum), Licorice (Glycyrrhiza glabra), purpurea), St. John's Wort (Hypericum perforatum), Cen Fennel (Foeniculum vulgare), Chaga (Inonotus obliquus), taury (Centaurium erythraea), Snowball tree berries (Vibur Thyme (Thymus vulgaris), Three-lobe Beggarticks (Bidens num opulus), Nettle (Urtica dioica), Dandelion (Taraxacum tripartite), Sage (Salvia officinalis), Dog rose (Rosa canina), officinale), Sweet-sedge (Acorus calamus), Oregano and Juniper berries (Juniperus communis). (Oreganum majorana), Marigold (Calendula officinalis), 0017. The second set (No. 2, set No. 2) essentially contains Seabuckthornberries (Hippophae rhamnoides), Elecampane flowers of Immortelle (Helichrysi arenarii), Barberry roots (Inula helenium), Tormentil (Potentilla erecta), Greater plan (Berberis vulgaris), Chicory roots (Cichorium intybus), Cori tain (Plantago major), Wormwood (Artemisia sp.), Siberian ander seeds (Coriandrum sativum), Marigold (Calendula golden root (Rhodiola rosea), Cudweed (Gnaphalium uligi officinalis), Wormwood (Artemisia sp.), and Maize cores with nosum), Licorice (Glycyrrhiza glabra), Fennel (Foeniculum Stigmas (Zea mays). vulgare), Chaga (Inonotus obliquus), Thyme (Thymus vul 0018. The third set (No. 2, set No. 3) essentially contains garis), Three-lobe Beggarticks (Bidens tripartite), Sage Barberry roots (Berberis vulgaris), Aronia berries (Aronia (Salvia officinalis), Dog rose (Rosa canina), and Juniperber melanocarpa), St. John's Wort (Hypericum perforatum), ries (Juniperus communis). Composition No. 4 can be com Centaury (Centaurium erythraea), Nettle (Urtica dioica), bined with Composition No. 2, sets 2 and/or 3. Common knotgrass (Polygonum aviculare), Wild strawberry leaves (Fragaria vesca), Greater celandine (Chelidonium BRIEF DESCRIPTION OF THE TABLES AND majus), and Immortelle (Helichrysi arenarii). FIGURES 0019. In one aspect, the composition can be simplified by eliminating duplicate ingredients. 0023 Table 1 is a summary of characteristics of patients at 0020 Such a multi-herb combination of three separate the initiation of a three-arm study to evaluate the effect of the formulations may have additional individual ingredients as composition No. 1 of the present invention on AIDS patients. will become evident from the detailed disclosure of the inven 0024 Table 2 shows the percentage of patients with clini tion. The compositions can be used alone or further combined cal adverse events considered as possibly related to treatment with first line TB drugs comprising isoniazid (H), rifampicin and of moderate or severe intensity. The study is the evalua (R), ethambutol (E), pyrazinamide (Z), and/or streptomycin tion of the effect of the composition No. 1 of the present (S). Also they can be combined further with second-line TB drugs including aminoglycosides such as: amikacin, or kana invention on AIDS patients. mycin; polypeptides including capreomycin, viomycin, or 0025 Table 3 shows the percentage of patients presenting enviomycin; fluoroquinolones such asciprofloxacin, or moxi with clinical opportunistic infections or co-infection defined floxacin; thioamides Such as ethionamide, or prothionamide; events during a 32-week treatment period. The study is the cycloserine; and/or para-aminosalicylic acid. Other TB drugs evaluation of the effect of the composition No. 1 of the present that can be used in further combination are: rifabutin; invention on AIDS patients. clarithromycin; lineZolid; thioacetazone; thioridazine; argin 0026 Table 4 describes changes in CD4 lymphocyte ine; vitamin D; and/or R207910 and/or derivatives thereof. counts, body weight and alanine transaminase (ALT) in 0021. Other embodiments relate to combinations of com patients with HIV. ponents. One embodiment (termed composition No. 3) 0027 Table 5 shows a summary of the effect of composi relates to compositions that include, as a first component, tion No. 1 on viral load decrease Aloe (Aloe arborescens), and as a second component at least 0028 Table 6 describes effect on body weight in patients one member selected from the group consisting of Common with TB. knotgrass (Polygonum aviculare), Yarrow (Achillea millefo 0029 Table 7 is a summary of results of treatment of lium), Purple coneflower (Echinacea purpurea), St. John's drug-resistant TB patients. Wort (Hypericum perforatum), Centaury (Centaurium eryth 0030 Table 6 describes radiological findings of TB raea), Snowball tree berries (Viburnum opulus), Nettle (Ur therapy in AIDS patients who have TB. tica dioica), Dandelion (Taraxacum officinale), Sweet-sedge (Acorus calamus), Oregano (Oreganum majorana), Marigold 0031 Table 8 shows culture and radiological findings in (Calendula officinalis), Seabuckthorn berries (Hippophae TB/HIV co-infected patients. rhamnoides), Elecampane (Inula helenium), Tormentil (Po 0032 Table 9 shows the effect on culture conversion and tentilla erecta), Greater plantain (Plantago major), Worm cavitary and miliary forms of TB. wood (Artemisia sp.), Siberian golden root (Rhodiola rosea), 0033 Table 10 shows the effectiveness of herbal combi Cudweed (Gnaphalium uliginosum), Licorice (Glycyrrhiza nation in patients with multi-drug resistant tuberculosis glabra), Fennel (Foeniculum vulgare), Chaga (Inonotus (MDR), extensively drug resistant TB (XDR), and in HIV/TB obliquus), Thyme (Thymus vulgaris), Three-lobe Beg co-infection. US 2008/0166435 A1 Jul. 10, 2008

0034 FIG. 1 shows changes in T-lymphocyte counts rela undue experimentation. One standard drop of an aqueous tive to baseline values. alcohol extract is about 0.03 ml. 0045. The herbs are typically dried and ground to a fine DETAILED DESCRIPTION powder. The composition can be an intimate mixture of pow 0035. The terms “medicinal plant,” “herb,” and “herbal.” ders that are formulated suitably such as pills or tablets. Such as used to describe the components of the invention, refer to pills can be made directly from powdered plants or formu materials of plant origin and can include without limit the lated from alcohol, for example, and water extracts by reduc leaves, stems, flowers, roots, and other plant parts, whether tion according to established procedures well-known in the fresh or preserved. A preferable method of preservation of art procedures. The preferred extraction method is water or herbs is by drying. In one aspect, the terms can refer to the alcohol or water-alcohol mixture either simultaneously or in leaves. consequent Subsequent steps as deemed necessary. The pro 0036. As used herein, an extract refers to the soluble phase portions of herbs to be mixed together generally range from of a mixture comprising an aqueous organic solvent contain about 1% to about 20% by weight of the composition, more ing one or more desired medicinal plants at a proportion preferably about 3% to about 5% by weight of the composi needed to extract the active principles of the herb. tion. The amount of alcohol is anywhere between 10-60% by 0037. The term “extracts,” as used to describe the inven weight if included at all in the present compositions. tion refers to extraction of useful components from herbs. 0046. In one aspect, the composition comprises a dried Any method of extraction known in the art can be used. A eXtract. preferred method of extraction is to mix a quantity of herb 0047. In one aspect, the following herbs in aqueous alco with a physiologically compatible solvent for at least a few hol extracts are preferred: marigold flowers (Calendula offi minutes, a few hours, or some days. cinalis), elecampane rhizome (Inula helenium), Seabuckthorn 0038. In one aspect, the solvent is a physiologically com fruit (Hippophae rhamnoides), potentilla rhizome (Potentilla patible organic solvent. Any physiologically compatible erecta), fennel fruit (Foeniculum vulgare), rhodiola rosea root organic solvent can be used, including, but not limited to ethyl (Rhodiola rosea), rose hips (Rosa canina), licorice root (Gly alcohol, isopropyl alcohol, glycerol, acetone, dimethyl Sul cyrrhiza glabra), juniper fruit (Juniperus communis), knot foxide, acetic acid, butyric acid, citric acid, ethyl acetate, grass (Paspalum distichum), aloe leaf (Aloe Vera), yarrow combinations thereof, and aqueous versions thereof A pre (Achillea millefolium), nettle leaf (Urtica dioica), St-Johns ferred physiologically compatible organic solvent is ethyl worth (Hypericum perforatum), plantain leaf (Plantago alcohol. Aqueous ethyl alcohol is more preferred, compris major), centaury (Centaurium erythraea), salvia leaf (Salvia ing, for example, 5% water and 95% ethyl alcohol. divinorum), oregano herb (Oreganum majorana), birch 0039. Any ratio of physiologically compatible solvent to (Betula pendula), wormwood (Artemisia sp.), flagroot rhi herb can be used. In one aspect, a ratio of from 1:1 to 1:10, by Zome (Acorus calamus), cudweed (Gnaphalium uliginosum), weight, is used. echinacea root (Echinacea angustifolia), thyme (Thymus 0040 Preferred physiologically compatible organic sol serpyllum), dandelion rhizome (Taraxacum officinale), bur vents are minimally toxic. By example, ethyl alcohol in the marigold (Bidens tripartite). amounts used in the therapy of the invention is considered 0048. Other plants equally suitable and which can be minimally toxic. added as ingredients of the instant invention can be selected 0041. The compositions of the invention show surprising from the group including but not limited to Adina piluifera, and beneficial immunomodulatory effects. Agrimonia eupatoria, Arbutus unedo, Arctostaphylos uva 0042. The compositions of the invention can be prepared ursi, Artocarpus heterophyllus, Catalpa bignoniodes, Catha with any amount of an herb in relation to another herb. In one ranthus roseus, Chimaphila umbellata, Cornusfiorida, Cor aspect, each herb is present in an equal amount by weight. In nus officinalis, Crataegus cuneata, Crataegus laevigata, another aspect, one herb is present at least ten times the Crataegus pinnatifida, Cryptostegia grandifolia, Elaeagnus amount of another herb. In yet another aspect, one herb is pungens, Eriobotrya japonica, Eucalyptus citriiodora, For present at one to ten times the amount of another herb. In still Sythia suspensa, Gaultheria fragrantissima, Glechoma hed another aspect, one herb is present at twice the amount of eracea, Hedyotis diffusa, Helichrysum angustifolium, Humu extract of another herb. lus lupulus, Hyssopus officinalis, Ilex paraguariensis, 0043. The compositions of the invention can also be pre Lavandula angustifolia, Lavandula latifolia, Leonurus car pared from extracts of herbs. In one aspect each extract is diaca, Ligustrum japonicum, Limonia acidissima, Lycopus present in an equal amount by Volume. In another aspect, an europeus, Malus domestica, Marubium vulgare, Melaleuca extract of one herb is present at more than ten times the leucadendra, Melissa officinalis, Mentha spicata, Mentha x amount of an extract of another herb. In yet another aspect, an rotundifolia, Monarda didyma, Nerium Oleander, Ocimum extract of one herb is present at one to tentimes the amount of basilicum, Ocimum basilicum, Ocimum basilicum, Ocimum extract of another herb. In still another aspect, an extract of basilicum, Ocimum canum, Origanum majorana, Origanum one herb is present at twice the amount of extract of another vulgare, Plantago asiatica, Plantago major; Plectranthus herb. amboinicus, Prunell vulgaris, Prunella vulgaris, Prunus 0044) The preferred dose can vary from one drop in new cerasus, Prunus laurocerasus, Prunus persica, Prunus sero born baby to 10-20 drops in adolescent and from 10 to 150 or tina spp serotina, Psidium guajava, Punica granatum, Pyrus more drops in an adult. The preferred range is between 10 to communis, Rhododendron dauricum, Rhododendron ferrug 50 drops once or twice per day. The most preferred route is ineum, Rhododendron ponticum, Rosmarinus officinalis, oral although topical application is equally suitable. One Rubus fruticosus, Salvia officinalis, Salvia Sclarea, Salvia skilled in the art can freely use other methods of delivery, and triloba, Sambucus nigra, Sanguisorba officinalis, Satureja such methods are within a skill of a practitioner that can be hortensis, Satureja montana, Sorbus aucubaria, Syring a vul experimentally determined by a routine practice without garis, Teucrium chamaedrys Teucrium polium, Teucrium spp. US 2008/0166435 A1 Jul. 10, 2008

Thevetia peruviana, Thymus serpyllum, Thymus vulgaris, 0051) To prepare a therapeutic mixture, 500 ml of each Uncaria tomentosa, Vaccinium corynobosum, Vaccinium extract is combined. myrtillus, Vaccinium vitis idaea, Verbena officinalis, Vibur num opulus var. opulus, Viburnum prunifolium, Vinca minor Example 2 or Zizyphus jujuba. Similarly, oleanolic acid is found in Achy ranthes aspera, Achyranthes bidentiata, Adina piluifera, Preparation of an Exemplary Herb Extract No. 2 Aipocynum cannabinum, Akebia quinata, Allium cepa, 0.052 For set No. 1 of Composition No. 1, one kilogram of Allium sativum, Arctostaphylos uva-ursi, Calendula officina each of the following dried herbs is separately ground to a lis, Catharanthus roseus, Centaurium erythraea, Chenopo powder. Aloe (Aloe arborescens), Common knotgrass dium album, Citrullus colocynthis, Cnicus benedictus, Cor (Polygonum aviculare), Yarrow (Achillea millefolium), nus officinalis, Crataegus pinnatifida Cyperus rotundus, Purple coneflower (Echinacea purpurea), St. John's Wort Daemonorops draco, Diospyros kaki, Elaeagnus pungens, (Hypericum perforatum), Centaury (Centaurium erythraea), Eleutherococcus senticosus, Eriobotrya japonica, Eugenia Snowball tree berries (Viburnum opulus), Nettle (Urtica dio caryophyllata, Forsythia suspensa, Glechoma hederacea, ica), Dandelion (Taraxacum officinale), Sweet-sedge (Acorus Harpagophtum procumbens, Hedera helix, Hedyotis diffusa, calamus), Oregano (Oreganum majorana), Marigold (Calen Helianthus annuus, Hemsley's amabilis, Humulus lupulus, dula officinalis), Seabuckthorn berries (Hippophae rham Hyssopus officinalis, Ilex rotunda, Lavandula latifolia, noides), Elecampane (Inula helenium), Tormentil (Potentilla Leonurus cardiaca, Ligustrum japonicum, Ligustrum luci erecta), Greater plantain (Plantago major), Wormwood (Ar dum, Liquidambar Orientalis, Liquidambar styraciflua, temisia sp.), Siberian golden root (Rhodiola rosea), Cudweed Loranthus parasiticus, Lufa aegyptiaca, Melaleuca leuca (Gnaphalium uliginosum), Licorice (Glycyrrhiza glabra), dendra, Melissa officinalis, Mentha spicata, Mentha x rotun Fennel (Foeniculum vulgare), Chaga (Inonotus obliquus), difolia, Momordica Cochinchinensis, Myristica fragrams, Thyme (Thymus vulgaris), Three-lobe Beggarticks (Bidens Myroxylon balsamum, Nerium Oleander, Ocimum suave, tripartite), Sage (Salvia officinalis), Dog rose (Rosa canina), Ociumum basilicum, Olea europaea, Origanum majorana, and Juniper berries (Juniperus communis). The powdered Origanum vulgare, Paederia Scandens, Panax ginseng, herbs are combined and suspended in 100 liters of 90% ethyl Panax japonicus, Panax quinquefolius, Patrinia scabiosaefo alcohol 10% distilled water. The suspension is agitated twice lia, Phytolacca americana, Plantago major; Plectranthus daily for three days. The suspension is then allowed to settle amboinicus, Prunella vulgaris, Prunus cerasus, Psidium and the supernate filtered to produce the extract, which is guajava, Pulsatilla chinenisis, Quisqualis indica, Rosmari stored in dark bottles. nus officinalis, Salvaia officinalis, Salvia Sclarea, Salvia tri 0053 For set No. 2 of Composition No. 2, one kilogram of loba, Sambucus migra, Satureja hortensis, Satureja montana, each of the following dried materials is separately ground to Swertia chinensis, Swertia diluta, Swertia mileensis, Syzy a powder: flowers of Immortelle (Helichrysi arenarii), Bar gium aromaticum, Thymus serpyllum, Thymus vulgaris, Tra berry roots (Berberis vulgaris), Chicory roots (Cichorium chycarpus fortunei, Uncaria tomentosa, Vaccinium corymbo inty bus), Coriander seeds (Coriandrum sativum), Marigold sum, Vaccinium myrtillus, Viburnum prunifolium, Viscum (Calendula officinalis), Wormwood (Artemisia sp.), and album, Vitis vinifera, and Zizyphus jujuba. The preferred Maize cores with stigmas (Zea mays). The powdered herbs botanical sources for ursolic acid is a member selected from are combined and suspended in 30 liters of 90% ethyl alcohol/ the group consisting of Ligustrum japonicum, Plantago asi 10% distilled water. The suspension is agitated twice daily for atica, Plantago major, Prunus species, Uncaria tomentosa, three days. The suspension is then allowed to settle and the Zizyphus jujuba, Cornus officinalis, Eucalyptus citriodora, supernate filtered to produce the extract, which is stored in Forsythia suspensa, Lavandula latifolia, Malus domestica, dark bottles. Nerium Oleander, Ocimum basilicum, Punica granatum, 0054 For set No. 3 of Composition No. 2, one kilogram of Pyrus communis, Rosmarinus officinalis, Salvia triloba, Sor each of the following dried materials is separately ground to bus aucubaria, Vaccinium myrtillus, Vaccinium vitis-idaea, a powder: Barberry roots (Berberis vulgaris), Aronia berries Viburnum opulus var. opulus, and Zizyphus jujuba. (Aronia melanocarpa), St. John's Wort (Hypericum perfora tum), Centaury (Centaurium erythraea), Nettle (Urtica dio EXAMPLES ica), Common knotgrass (Polygonum aviculare), Wild Straw 0049. The following examples illustrate aspects of the berry leaves (Fragaria vesca), Greater celandine invention, but do not limit the scope. The scope of the inven (Chelidonium majus), and Immortelle (Helichrysi arenarii). tion is defined by the claims. The powdered herbs are combined and suspended in 40 liters of 90% ethyl alcohol/10% distilled water. The suspension is Example 1 agitated twice daily for three days. The Suspension is then allowed to settle and the supernate filtered to produce the Preparation of an Exemplary Herb Extract No. 1 extract, which is stored in dark bottles. 0050. One kilogram of each of the following dried herbs is 0055. The extracts are stored for up to a year at 15 to 24°C. separately mechanically pulverized: Inula helenium, Foen– To produce a therapeutic solution, two liters of set No. 1 is iculum vulgare, Juniperus communis, Glycyrrhiza glabra, combined with one liters each of set No. 2 and set No. 3. Oreganum majorana, Calendula officinalis, Rosa Canina, and Thymus serpyllum. Each of the powdered herbs is separately Example 3 mixed and suspended in 5 liters of 95% aqueous ethyl alcohol Patient Population HIV Studies with occasional agitation for two days. Each Suspension is decanted, the respective Supernate is filtered through a paper 0056. In this trial, 70 male or female adults with HIV/ filter, and the extract is collected. Each extract is stored in AIDS were enrolled. SeeTable 1. Most of them were hepatitis dark bottles at about 20° C. for up to a year. virus C (HCV) co-infected, with a significant proportion of US 2008/0166435 A1 Jul. 10, 2008

them Suffering from alcohol abuse or/and drug addiction. CD4 counts increased progressively in all arms, reaching Significant metabolic disorders and underlying hepatic injury +108, +85, and +103 cells/mm by 20 weeks, and +102, +190 caused by chronic alcohol, drug addiction, and hepatitis co and +175 cells/mm by 32 weeks, for arms A, B and Crespec infection were common for this study cohort. At study initia tively (OT analysis). tion 21% had active opportunistic infections and 71% had 0061 There was a significant difference between arm A grade 3 or more laboratory or clinical abnormalities. Patients compared with arms B and C in terms of change in CD4 were divided into three arms, with comparable baseline char counts from baseline to week 12. In arm A CD4 cell counts acteristics. All participants were antiretroviral drug naive. increased significantly compared with arm B, in which cell Each participant provided an informed consent and was free counts decreased (A versus B; p-0.04) and with arm C, where to withdraw from the study at any time. All patients were the increase in CD4 count was not significant compared to given symptomatic therapy for opportunistic infections if baseline level (A versus C; p <0.05). required. The trial was designed to continue until the last 0062. The first statistically significant increase in CD4 enrolled patient reached 48 weeks on therapy. counts from baseline was observed in groups B and Cat week 20. By week 32 progressive increase in CD4 cells in these two Treatment Regimen groups was higher than in arm A (B versus A, p<0.05, and C 0057. After initial screening, qualifying patients were ran versus A; p<0.05). domly divided in three arms. Each patient in arm. A was 0063 Arm Chad three patients in a terminal stage of AIDS prescribed zidovudine (AZT) in 300 mg doses twice-daily, and who had very low levels of CD4 cells count at baseline: lamividine (3TC) 150 mg tablets twice-daily, and efavirenz 65, 64, and 128 cells/mm, respectively. After treatment ini (EFV) 600 mg dose once daily. Each patent in arm B received tiation CD4 cells rose, reaching +15, +111 and +1.94 cells/ the same antiretroviral therapy plus the composition No. 1 of mm by 12 weeks, and +85, +103 and +1171 cells/mm by 20 the present invention given as 50 drops added to a glass of weeks. In parallel with rising CD4 cell counts these patients water, twice-daily. The arm C patients received the same experienced progressive clinical improvement. immunomodulator of the present invention as monotherapy in the same 50 drops twice-daily dose. Adverse Events Evaluation 0064 Over 32 weeks of treatment significant differences were observed between arm A as compared with arms B and 0058 Parameters including as CD4 cell counts, AIDS C in terms of overall incidents of adverse events. At least one defining events, relapse and new events of opportunistic adverse event, which possibly and probably was related to the infection (OI), adverse events, and laboratory parameters study medications, was reported in 65, 24, and 5% of patients were assessed at baseline and at weeks 12, 20, and 32. For in arms A, B, and C respectively. Most clinical adverse events patients with clinical signs of adverse events laboratory tests were mild gastrointestinal symptoms were the most fre were performed every two weeks. Baseline values for CD4 quently reported adverse events. Over 32 weeks period, the cells counts were defined as the average of the last screening most common adverse events considered as possibly related and last baseline values. Adherence to treatment was assessed to study medication as well as those of moderate or severe at each visit. Adverse events were graded by intensity and intensity are shown in Table 2. There were clear differences their relationship to the study medications. AIDS defining between arms in the pattern or incidence of adverse events: adverse events (as per 1993 Center for Disease Control defi the levels of diarrhea and nausea were significantly higher in nitions of AIDS) were recorded in the same way as all other arm. A compared with arm B. In contrast, in arm C gastrointes adverse events. Laboratory abnormalities were graded. tinal symptoms were not observed throughout the study period. Occurrences of headache and fatigue also were sig Statistical Analysis nificantly higher in arm. A when compared with arm B and 0059. The primary outcome measure was CD4 cells count, these symptoms were not observed in arm C. Seven patients levels of adherence, incidence of HIV related events, other (35%) in arm A experienced serious adverse events, which adverse events, and laboratory abnormalities. The trial was were considered to be possibly or probably related to study designed to compare arm. A with arms B and C at weeks 12, medication. In this arm 1 patient (5%) refused further therapy 20, 32 and 48, using the proportion of patients. All statistical and 6 patients (30%) needed replacement therapy due to tests were performed as on the intent-to-treat (ITT) popula progressive fatigue, vomiting and gastrointestinal disorders, tion, which included all patients who took at least one dose of and/or hepatotoxicity. In arms B and C no incidents of inter study medications. Patients who discontinued for any reason ruption or changing therapy were observed. There were also were considered as treatment failures. Tests were performed significant differences between three arms in respect to labo on the on-treatment (OT) population, which included only ratory findings (Table 2). those patients with available evaluation at that time point. The safety evaluation included all patients who had at least one Opportunistic or Co-Infection Defined Events post-baseline safety assessment. 0065 During the 32 week reporting period, opportunistic infections (OI) were observed in all three arms under therapy. Change in CD4 Cell Counts OI were observed in 6 (30%), 4 (13%) and 4 (20%) patients 0060 Significant increases from baseline were seen in all for A, B and C arms, respectively (Table 3). There was a clear three arms at every assessed time point. By the end of first 12 distinction between treatment arms in terms of frequency OI weeks of treatment, CD4 cell counts changed as follows: in and co-infection events. These events were significantly arm. A reaching +122 cells/mm; in arm B decreasing but not higher in arm. A compared with arms B or C. significantly, -10 cells/mm; and in arm C increasing +36 0.066 Among the most frequently reported relapses of OI cells/mm, but not in a significant manner. On the follow-up and co-infection were oral or esophageal candidiasis 4 (20%), US 2008/0166435 A1 Jul. 10, 2008

2 (7%), and 2 (10%), herpetic infections 4 (20%), 4 (13%) and on standard ART therapy gained lowest number of cells when 3 (15%) patients in the arms A, B and C respectively. Acute compared to Band C arms, i.e., + 102, +190, and +175 cells/ tuberculosis was observed in 2 (10%) and 2 (7%) patients in 3. arms A and B, respectively. Similarly, the relapses of hepatitis 0071. Additional parameters under consideration were the C were observed only in arms A and B, 2 (10%) and 1 (3%), incidence of adverse events, frequency of opportunistic infec respectively. tions and co-infections, liver function test, and effect on body weight. The incidence of adverse events which possibly and Effect on Liver Function probably were related to the study medications was lowest in the composition No. 1 of the present invention arm (5%) 0067 Most patients enrolled in study had underlying liver when compared to standard AZT/3TC/EFV tri-therapy pathology. Signs of progressing chronic inflammatory pro (65%). Interestingly, patients in arm B who were both treated cess in liver caused by persistent viral infection, toxicity, and with AZT/3TC/EFV and the composition of present invention alcohol were registered as mean values of standard liver func had significantly lowerincidence (24%) of adverse events and tion test (LFT). Baseline ALT or/and AST were elevated in hepatotoxicity despite exposure to the same ART dose as in 7/20 (30%), 13/30 (43%), 11/20 (55%) patients in arms A, B, arm A. and C, respectively. Mean baseline values for ALT were 36, 0072 Surprisingly, the composition No. 1 of the present 62, and 72 U/L, respectively. The median cumulative change invention seems to normalize elevated liver enzyme levels. At from baseline ALT values were +22, +18 and -16 U/L at 12 treatment initiation baseline values for ALT were 36,62, and weeks, +30,-36, and -34 U/L by week 20, and +42, -24,-41 72 U/L but at week 32 ALT values have increased to a mean U/L by week 32 for arms A, B, and C, respectively. At week 78 U/L in arm. A but declined to 38 and 31 U/L in B and C 32 ALT values have increased to a mean 78 U/L in arm A and arms. These properties of the composition of present inven declined to 38 and 31 U/L in arms B and C, respectively. The tion are of major consequence to management of ART toxic difference between arms B and C compared with arm A in ity. In addition to iatrogenic hepatotoxicity that ranges from terms of ALT values (B versus A; p<0.05, C versus A; p<0. mild hepatitis to liver failure there is a significant threat in 03). In arm C ALT values were decreasing progressively form of chronic viral hepatitis, i.e., HCV and HBV with under therapy and became significantly lower than baseline higher risk of morbidity and mortality. Almost half of patients levels (P<0.01). Similar trends were observed with AST participating in this trial had confirmed HCV infection. How marker. The meanbaseline values of AST were 42,49, 58 U/L ever, despite the lack of hepatitis-specific treatment, patients for arms A, B and C, respectively. At week 32 ALT values who were given composition No. 1 of the present invention, increased to a mean 68 U/L in arm A and decreased to 42 and experienced normalization of initially high ALT and AST 26 U/L in arms B and C, respectively. The number of patients levels without a single incident of relapse. In contrast patients with ART related hepatotoxicity was 6 (30%) and 2 (10%) on AZT/3TC/EFV had higher incidence of hepatitis relapses. patients in arm A and B respectively. In arm C no cases of The patients on the same ART regimen supplemented with the drug-related hepatotoxicity were noted. composition of present invention had a lower number of outbreaks and a normalized liver function test. These obser Effect on Body Weight vations indicate clearly that the composition No. 1 of the present invention possesses anti-inflammatory activity. 0068 Mean values for baseline body weight were 64.2-8. 0073 AIDS-associated wasting is the major factor that 9; 68.9+7.6: 67.3+8.4 kg for arms A, B, and C. Among arms contributes to morbidity and mortality. Currently, there is no A, B, and C 7 (35%), 11 (33%), 6 (30%) patients had standard treatment for this condition, which remains poorly cachexia. The body mass steadily increased during therapy, treatable even in countries with advanced medical care. Some reaching 1.4; 6.9; and 5.1 kg gain at week 32 for arms A, B, nutritional regimens yield positive results, however their Suc and C, respectively. Weight gain varied for every patient cess has been unpredictable. Weight gain observed with the ranging from 0.5-2 kg up to 6-9 kg during the therapy period. composition No. 1 of the present invention was significantly At the end of study, the mean weight values were 65.6+7.3: higher when compared to Such Supplements or ART therapy. 75.8+6.9; 72.4+8.6 kg for arms A, B, and C respectively. This weight-correcting property alone represents a significant Further results are shown below and in Table 4. achievement that greatly augments the choice of available 0069. Several chemical anti-HIV agents have been devel treatment options. oped. However, besides the high cost, there are adverse 0074 Currently, several immunotherapeutic approaches effects and toxicity associated with use of chemotherapy. are available. So far most of these therapies are in the domain Herbal medicines have frequently been used as alternative of so-called therapeutic vaccines and related immunothera means of therapy by HIV positive individuals and AIDS pies. Very few validated, immune-based interventions are patients. Except for a few instances, there is insufficient evi available when it comes to products of plant origin. Most dence to support the benefit of plant-derived medicines. studies in this area concern Oriental medicinal plants some of Potential beneficial effects of medicinal plants need to be which were used for treatment of autoimmune disorders such confirmed by rigorous clinical trials, preferably by compar as habitual abortion. However, there are no examples of appli ing them to standard ART as in the present study. cation of autoimmunity-regulating herbs in infectious dis 0070 The safety and efficacy of immunomodulator com eases, especially HIV infection. Not every herbal preparation position No. 1 of the present invention is compared to stan can possess the right property Suitable for Such an indication. dard antiretroviral therapy AZT/3TC/EFV or combination of Indeed, some herbal Supplements were shown to exacerbate AZT/3TC/EFV with the composition of present invention autoimmunity—a property contrary to the intended action of using as the primary endpoint the change in CD4 lymphocyte the compositions of the present invention. On the other hand counts. The increase from baseline in CD4 cells was seen in it would be a mistake to classify the composition No. 1 of the all three arms at every assessed time point. However, patients present invention as an immunosuppressant. The decrease in US 2008/0166435 A1 Jul. 10, 2008 the frequency of opportunistic infections and absence of new aqueous-alcohol extract from medicinal plants from compo episodes of OI as demonstrated in this trial, indicate that the sition No. 2, set No. 1. The second preparation was compo composition No. 1 of the present invention does not compro sition no. 2, set No. 2. The third multi-herb composition was mise the immunity, whether acquired or native. These con composition No. 2, set No. 3. siderations are intriguing not only from the immunological 007.9 The duration of treatment ranged between 10.6- point-of-view but are also important in finding effective 30.3 weeks with average/median 16.2/16 weeks (Table 10). therapeutic solutions for diseases which so far have been The treatment lasted until patients were discharged from the refractory to existing choices of treatment. dispensary upon twice-repeated negative culture findings and 0075 Thus, the composition No. 1 of the present invention clinical and radiological improvements. The time to negative displays a broad-spectrum clinical activity that has far-reach culture conversion ranged between 9-62 days with mean/ ing implications. It reduces drug toxicity and improves ART median 30.6/30 days. Mycobacterial clearance was con efficacy when used in combination with standard ART. It firmed by repeated cultures at monthly intervals. enhances anti-HIV activity of ART. It enhances the anti-HIV 0080. There was no difference between chronic, previ activity of ART. Further studies are required to identify the ously treated TB versus first-diagnosed TB cases in terms of mechanism of action and additional benefits associated with days to discharge, i.e., 111.6 vs 114.8 (p=0.42) or days to its use. mycobacterial clearance, 33.7 vs 28 (p=0.16). A similar 0076. In addition to use of the composition No. 1 of the stratification analysis comparing TB/HIV with TB alone invention alone it is also contemplated to use it in combina patients reveals that patients with dual infection appear to tion with one or more compounds selected from the group require longer treatment, i.e., 127.9 vs 105.5 days, but the consisting of HIV reverse transcriptase inhibitors, protease difference was not statistically significant (p=0.15). Simi inhibitors, integrase inhibitors, fusion inhibitors, viral entry larly, negative culture conversion occurred about nine days inhibitors, vaccines, therapeutic vaccines, and/or other later in TB/HIV individuals than in TB patients, i.e., 36.1 vs known immunomodulators, as deemed necessary to a prac 27.5 days, but the difference was not statistically reliable ticing physician skilled in the art. For example reverse tran (p=0.08). The comparison of treatment outcomes between 15 Scriptase inhibitors can be selected from the group including drug-resistant and 5 drug-sensitive cases also failed to reveal nucleoside RT inhibitors: Retrovir (AZT/zidovudine; Glaxo statistical difference. Time to negative culture was 30.3 vs Wellcome); Combivir (GlaxoWellcome); Epivir (3TC, lami 31.4 days and time to discharge 106.2 vs 134.8 days with Vudine: Glaxo Wellcome); Videx (ddI/didanosine; Bristol probability values p=0.4 and p=0.18 respectively. These find Myers Squibb); Hivid (ddC/zalcitabine; Hoffmann-La ing indicate that when ATT is combined with the composition Roche); Zerit (d4T/stavudine: Bristol-Myers Squibb); Ziagen No. 2 herbals its efficacy is enhanced since normally ATT is (abacavir, 1592U89; Glaxo Wellcome); Hydrea (Hydrox not effective when patients with drug-resistant TB and/or yurea/HO; nucleoside RT potentiator from Bristol-Myers HIV are treated. Squibb) or Non-nucleoside reverse transcriptase inhibitors I0081. At the end of study almost every patient had gained (NNRTIs): Viramune (nevirapine; Roxane Laboratories); substantial lean body mass—an effect that was evident within Rescriptor (delavirdine; Pharmacia & Upjohn); Sustiva one month from initiation of the therapy. One TB/HIV patient (efavirenz, DMP-266: DuPont Merck); Preveon (adefovir (#19) lost 10 kg, but all other patients gained weight, ranging dipivoxil, bis-POM PMEA: Gilead). Protease inhibitors between 3 and 17 kg. The average accrual in lean body mass (PI's) can be selected from Fortovase (saquinavir; Hoffmann was 8.7 kg (median 9.5 kg), which was statistically highly La Roche); Norvir (ritonavir; Abbott Laboratories); Crixivan significant as evidenced by paired Student t-test (p=0. (indinavir, Merck & Company); Viracept (nelfinavir, Ago 0000008). uron Pharmaceuticals); Angenerase (amprenavir/141W94: I0082. The potential hepatotoxicity of ATT when used in Glaxo Wellcome), VX-478, KNI-272, CGP-61755, and combination with herbal preparations was monitored by U-103017. Other inhibitors not listed here but from the fami quantitative liver function tests. Surprisingly, despite inten lies of drugs used in antiviral therapy are contemplated as sive chemotherapy, patients have shown signs of better liver well. function. The level of total bilirubin had decreased from mean 15.5 to 11.6 umol/L a favorable change that was statisti Example 4 cally significant (p=0.009). Similarly, the values of alanine Treatment of Tuberculosis Patients transaminase (ALT), another marker of liver damage, declined from abnormally high (53.1 IU/L) to normal levels 0077. Further studies were carried out on patients suffer (30.4 IU/L)—a change that was also statistically significant ing from tuberculosis. The study parameters are provided in (p=0.01). Tables 5-6 and results of the study are provided in Tables 7-9. I0083. Another phenomenon observed during therapy is a Table 10 shows conclusions. reversal of the baseline anemic state and pro-inflammatory 0078. Open-label, salvage anti-tuberculosis therapy condition—which are symptoms very common in TB and (ATT) combined with immunomodulators from medicinal HIV. Most patients at Study entry displayed signs of anemia plants, was conducted in 20 patients, comprising seven who and had abnormally elevated leukocyte counts. At the end of had HIV co-infection. Excepting five patients with HIV, all treatment these parameters were improved in a statistically other individuals had multidrug-resistant TB (MDR-TB) significant manner. The levels of hemoglobin had risen from including 7 (35%) patients with XDR-TB. Patients hospital 103.2 to 117.3 g/L (p=0.00005), whereas leukocyte counts ized in a TB dispensary were treated TB drugs under directly returned back to normal levels from 8.9 to 6.9x10 cells/L. observed therapy (DOT) until repeated negative culture con (p=0.003). version and recuperation from radiological and clinical I0084 Flow cytometry measurements of T lymphocyte symptoms. Three phytopreparations were used in addition to counts conducted at study entry and at the end of follow-up standard TB therapy as adjunct immunotherapy. The first had were available in 6 of 7 TB/HIV patients. The helper CD4+ US 2008/0166435 A1 Jul. 10, 2008

cells declined in two patients, while the remaining patients and decline in CD8 cells resulted in an almost doubled ratio of displayed an increase in their lymphocyte numbers. When CD4/CD8 cells, i.e., from baseline 0.475 to 0.848 at the end of calculated for the total population there was an increase at the study (p=0.03). See FIG. 1. I0085. The composition No. 2 of the invention may be end of the study compared to baseline levels. From an average useful not only for HIV and TB as demonstrated convincingly of 371 cells/ul at baseline they have risen to 566 cells/ul—an above but for treatment of other ailments as well. Besides increase equal to 52% (p=0.07). The absolute numbers of being useful for human treatment, these compounds are also CD8+ T-lymphocytes appeared to decline but no statistical useful for veterinary and lab animal use, including horses, significance was reached (p=0.1). The increase in CD4 cells dogs, cats, rats, mice, sheep, and pigs.

TABLE 1. Summary of HIV+ patients at study initiation

Arm B (N = 30) AZT/3TC/EFV + Arm C (N = 20) Arm A (N = 20) Composition of Composition of AZT3TCEFV present invention present 600/300/600 mg 600/300/600 mg + invention daily 100 drops daily 100 drops daily N(%) N(%) N(%)

Characteristics

Male 8(40%) 18(59%) 16(80%) Female 12(60%) 12(41%) 4(20%) Body weight Meant SD 64.2 + 8.9 kg 68.9 + 7.6 kg 67.3 + 8.4 kg CD4 cell counts (cells/mm) 361 421 462 Prior antiretroviral therapy (%) O O O Patients with TB 7(35%) 7(23%) 9(45%) Hepatitis C or B 9(45%) 11(33.3%) 12(50%) Oral or esophageal candidiasis 7(35%) 19(62.7%) 15(75%) Herpes Zoster 5 (25%) 7(23%) 11(55%) Laboratory shift abnormalities Neutrophils 1(5%) 2(7%) Aspartate aminotransferase 6(30%) 11(33%) 7(35%) Alanine aminotransferase 7(35%) 9(29%) 8(40%) Hemoglobin 2(10%) 2(7%) 1(5%)

TABLE 2 Percentage of patients with clinical adverse events considered as possibly related to treatment and of moderate or severe intensity. Arm B (N = 30) AZT3TCEFV Composition of Arm C (N = 20) Arm A (N = 20) the present the composition of AZT3TCEFV invention present invention 600/300/600 mg 600/300/600 mg + monotherapy daily 100 drops daily 100 drops daily Adverse events N(%) N(%) N(%) Diarrhea 6(30%) 2(7%) Nausea 7(35%) 2(7%) Vomiting 2(10%) Abdominal pain 7(35%) 3(10%) Headache 3(15%) 1(3%) 1(5%) Peripheral neuropathy Fatigue 11(55%) 3(10%) 1(5%) Laboratory abnormalities Neutrophils 2(10%) Aspartate 5 (25%) 1(3%) aminotransferase Alanine aminotransferase 6(30%) 2(6%) Haemoglobin 2(10%) Cholesterol 2(10%) US 2008/0166435 A1 Jul. 10, 2008

TABLE 3 Percentage of patients presenting with clinical OI or co-infection defined events during 32 weeks treatment period Arm B (N = 30) Arm A (N = 20) AZT/3TC/EFV + Arm C (N = 20) AZT3TCEFV the composition No. composition No. 1, 600/300/600 mg daily 1, 100 drops daily 100 drops daily OI and co-infections N(%) N(%) N(%) Oral esophageal 4(20%) 2(7%) 2(10%) candidiasis Herpes 4(20%) 4(13%) 3(15%) Tuberculosis 2(10%) 2(7%) Cachexia 3(15%) Hepatitis C 2(10%) 1(3%)

TABLE 6 TABLE 4 Effect of two separate treatments CD4 counts ALT values Body weight Oil bodyOCW Wellweight in patients8CSW with TB Body weight Weight Patients Before After Before After Before After prior to Proportion change after 6 TBJHIV therapy of patients months on Arm A 361 463 36 USL 78 USL 642 65.6 Patients (kg it SD) with cachexia therapy Arm B 421 611 62 USL 38 UAL 68.9 75.8 TB drugs + S25.7 -8.5 - 2.7 +2.7 kg Arm C 462 637 72 USL 31 USL 67.3 72.4 spon No. 2 (n = 12) = TB drugs (n = 20) 64 6.3 -52 - 1.7 -0.6 kg (n = 13) TABLE 5 Effect of therapy with antiviral drugs (ART) without or with herbal composition on HIV-RNA plasma levels

ArmB Arm A HIV patients on ART + Herbal HIV patients on ART alone (N = 20 composition (N = 20

HIV-RNA HIV-RNA Difference HIV-RNA HIV-RNA Difference Patient copies/ml at copies/ml at compared to copies/ml at copies/ml at compared to No. baseline 2nd month baseline baseline 2nd month baseline

1 847.2 473.5 -373.7 952.2 421.2 -531 2 1756.8 1308.3 -448.5 1353.0 789. -563.9 3 978.1 1123.6 --145.5 ND ND ND 4 2564.3 1141.2 -1423.1 3899.1 1854.4 -2044.7 5 345.4 96.1 -249.3 818.4 379. -439.3 6 2O53.O 1845.1 -2O7.9 1938.0 956.3 -9817 7 763.2 1295.1 --531.9 2SO1.4 2296. -2O5.3 8 1537.0 867.1 -669.9 783.5 1394.6 +611.1 9 894.2 778.0 -116.2 464.3 235. -229.2 10 7442.1 7601.4 --159.3 937.3 S62. -375.2 11 346.4 189.3 -157.1 1558.1 1415.4 -142.7 12 3178.2 2723.1 -455.1 10136.5 1O112. -24.4 13 237.0 91.3 -145.7 539.O 241.3 -297.7 14 881.3 922.4 +41.1 669.4 3.14.2 -355.2 15 1045.O 851.1 -193.9 1749.4 958.2 -791.2 16 2339.3 1911.O -428.3 973.6 689. -284.5 17 473.1 529.4 --56.3 889.7 564.2 -32S.S 18 3O88.2 2O64.3 -1023.9 2377.1 1918.4 -458.7 19 ND ND ND 2S4.5 99.4 -155.1 2O 1865.5 1141.1 -724.4 1271.3 788.3 -483 Statistics Mean: SD = Mean SD = Meant Mean SD = Mean SD= Meant 1717, 1660 1419 - 1650 SD = -299 448 1792 - 22O2 1368 - 2208 SD = -425 - SO7 Geometric Geometric Geometric Geometric Geometric Geometric mean = 1199 mean = 876 mean = 272 mean = 1222 mean = 762 mean = 353 Median = 1045 Median = 1124 Median = -208 Median = 974 Median = 788 Median = -355 Wilcoxon Wilcoxon signed rank signed rank test: test: P = 0.008 P = O.OO1

ND: not done US 2008/0166435 A1 Jul. 10, 2008

TABLE 7 TABLE 8 Results of treatment of drug-resistant TB patients. Culture and radiological findings in TB/HIV co-infected patients Time to Response to therapy by Culture Culture Healing of negative - radiology- TB/AIDS patient negative negative cavities Groups 2nd month 3rd month 3rd month Drug-resistant TB culture in Negative New TB Chronic TB patients sputum culture diagnosis form TB drugs + 648% 82.7% 368% TB drugs + 3.5-4 months 80% 89% 70% composition No. 2 composition No. 2 (n = 33) (n = 40) TB drugs 188% 21.7% 33% TB drugs (n = 40) 5.8-6 months 30% 29% 10% (n = 33)

TABLE 9

Effect on culture conversion and cavitary and miliary forms of TB

Arm A (n = 20): ATT Arm B (n = 20): ATT + Herbal composition No. 2

Percent Percent Primary Patients at Time of Patients at Time of P Endpoints baseline Responders (weeks) response baseline Responders (weeks) response value

Smear and 19 New 3 20-24 16% 18 New 9 16 67% O.OO3 culture findings Chronic O Chronic 3 24 Cavitary and 16 40 24-28 25% 15 9 16-18 60% O.O2S destructive TB Miliary and infiltrating 15 7 24-28 46% 13 11 16-18 84% O.O46 TB

TABLE 10 Characteristics of TB patients treated with ATT in combination with herbals TB Days drug HIV status Days to Leukocytex TB resis- AIDS Oil negative 1OL

No. Sex Age infection tance Stage DOT culture before after

1 S4 M 30 Primary MDR 74 10 9.4 12 HARAZ.O 2.57 M 58 Primary MDR 122 30 9.8 6 RETH CPXPFX 3,73 M 38 Chronic MDR 131 30 14 6 SHAETH PAS 4f78 F 40 Primary MDR 77 9 10 5.2 HARAK PAS Prothio 5/92 M 32 Primary MDR 122 55 5.8 6 HAEFPAS, RFB 6,492 M 47 Chronic MDR 75 28 8 6.8 HARAEK 7.56 M 42 Primary XDR 74 23 11.6 8.1 HARAE KFOPAS US 2008/0166435 A1 Jul. 10, 2008 11

TABLE 10-continued

Characteristics o TB patients treated with ATT in combination with herbals 864 M 47 Primary XD 133 22 9.1 9.1 HARSFK LP 9.68 M 52 Primary XD 117 37 11 6 HRA PFXPAS 0.84 M 44 Primary XD 143 34 4.5 6.8 HARETH KFLPAS 1,156 M 25 Chronic XD 89 25 8.2 6 HARZAK OAPAS 2,532 M 48 Chronic XD 122 35 8.8 5.3 HRKA OPAS 3,627 M 35 Primary XD 93 2O 9 10 HRKA CPXPFX 4,59 M 47 Primary — +III 212 34 6.8 6.9 Sf 61 M 39 Chronic — +III 107 38 6.5 4.9 6, 161 F 34 Chronic — +III 98 34 5.4 5.2 7,185 F 24 Chronic — +III 74 24 6.5 7.3 8,295 M 45 Chronic — +III 183 27 9 6.8 9/72 M 27 Chronic MDR +III 125 62 11 6.2 HKAf PAS 20,481 F 39 Primary MDR +III 96 34 13.3 7.1 HARK Prothio Sl 4f16 39.79.2 9/11. 5.15 713 113.4 36.7 30.6 - 12.5 89 2.5 6.9 1.8 Mean decrease = Mean gain = 2x 109 L 14.1 g/L P = 0.003 P = OOOOOS

Weight Total ALT Hb g/L change kg bilirubin IUL

No. before after before after before after before 8t

1,54 82 O4 60 68 32.4 1.7 37 50 2/57 2O 23 66 78 4 O.S 37 50 3,73 O8 2O 52 68 6.3 O.S 62 2 4f78 OO 6 52 56 4 O.S 25 2 5/92 10 22 75 85 O.S 0.7 50 2 6,492 O6 22 66 78 4 9.7 75 50 7/56 22 4 59 68 O.S 1.7 25 50 864 O8 6 52 62 1.7 0.7 62 2 9.68 OO 8 64 74 1.7 0.4 75 2 1084 2O 8 63 69 8.6 O.S 12 50 11,156 09 2O 65 78 O.S O.S 62 2 12,532 88 22 72 78 4 O.S 37 2 13,627 88 8 50 63 32.4 O.S 25 2 14,59 28 8 77 8O 1.7 O.S 50 50 15,61 O6 2 65 76 O.S 1.5 75 50 16, 161 05 8 58 67 20.9 O.S 42 2 17,185 95 8 63 70 O.S O.S 75 50 18,295 94 2O 61 68 8.6 8.6 112 50 1972 O2 6 76 66 6.4 O.S 37 2 20,481 72 O 43 60 1.7 O.S 87 37 Sl 103.214 117.3 4.6 61.99.1 70.6 - 7.5 15.5 - 6.5 11.6 2.6 53.127 3O4 17.5 Mean gain = Mean decrease = Mean decrease = 8.7 kg 3.9 Imol/L 22.7 IUL P = O.OOOOO9 P = 0.009 P = 0.001

*Criteria for definition of XDR are as per WHO recommendation. ATT drugs are abbreviated as follows: Isoniazid (H), Rimfapicin (R), Pyrazinamide (Z), Ethambutol (E), Streptomycin (S), Levofloxacin (L), Ofloxacin (O), Ciprofloxacin (CPX), Pefloxacin (PFX), Kanamycin (K), Amikacin (A), Paraaminosalicylic acid (PAS), Rifabutin (RFB), Ethionamide (ETH), Prothionamide (Prothio) US 2008/0166435 A1 Jul. 10, 2008

We claim: (Polygonum aviculare), Yarrow (Achillea millefolium), 1. A composition consisting essentially of plant material Purple coneflower (Echinacea purpurea), St. John's Wort from Inula sp., Foeniculum sp., Juniperus sp., Glycyrrhiza (Hypericum perforatum), Centaury (Centaurium erythraea), sp., Oreganum sp., Calendula sp., Rosa sp., and Thymus sp., Snowball tree berries (Viburnum opulus), Nettle (Urtica dio or an extract thereof. 2. The composition according to claim 1, wherein one or ica), Dandelion (Taraxacum officinale), Sweet-sedge (Acorus more of the ingredients of the extract are selected from the calamus), Oregano (Oreganum majorana), Marigold (Calen group consisting of Inula helenium, Foeniculum vulgare, dula officinalis), Seabuckthorn berries (Hippophae rham Juniperus communis, Glycyrrhiza glabra, Oreganum majo noides), Elecampane (Inula helenium), Tormentil (Potentilla rana, Calendula officinalis, Rosa Canina, and Thymus serpyl erecta), Greater plantain (Plantago major), Wormwood (Ar lum. temisia sp.), Siberian golden root (Rhodiola rosea), Cudweed 3. The composition of claim 1 wherein the extract is an (Gnaphalium uliginosum), Licorice (Glycyrrhiza glabra), aqueous alcohol extract. Fennel (Foeniculum vulgare), Chaga (Inonotus obliquus), 4. A composition consisting essentially of an alcohol-water Thyme (Thymus vulgaris), Three-lobe Beggarticks (Bidens extract of plant material from Aloe (Aloe arborescens), Com tripartite), Sage (Salvia officinalis), Dog rose (Rosa canina), mon knotgrass (Polygonum aviculare), Yarrow (Achillea Juniper berries (Juniperus communis), Barberry roots (Berb millefolium), Purple coneflower (Echinacea purpurea), St. John's Wort (Hypericum perforatum), Centaury (Centaurium eris vulgaris), Chicory roots (Cichorium intybus), Coriander erythraea), Snowball tree berries (Viburnum opulus), Nettle seeds (Coriandrum sativum), Maize cores with Stigmas (Zea (Urtica dioica), Dandelion (Taraxacum officinale), Sweet mays). Aronia berries (Aronia melanocarpa), Wild straw sedge (Acorus calamus), Oregano (Oreganum majorana), berry leaves (Fragaria vesca), Greater celandine (Chelido Marigold (Calendula officinalis), Seabuckthornberries (Hip nium majus), or Immortelle (Helichrysi arenarii) or an extract pophae rhamnoides), Elecampane (Inula helenium), Tormen thereof. til (Potentilla erecta), Greater plantain (Plantago major), 7. The method of claim 5 further comprising improvement Wormwood (Artemisia sp.), Siberian golden root (Rhodiola rosea), Cudweed (Gnaphalium uliginosum), Licorice (Gly of a disease characteristic, wherein the disease characteristic cyrrhiza glabra), Fennel (Foeniculum vulgare), Chaga (In is selected from the group consisting of anemia, leucopenia, onotus obliquus), Thyme (Thymus vulgaris), Three-lobe inflammation, autoimmune condition, viral load, adverse Beggarticks (Bidens tripartite), Sage (Salvia officinalis), Dog event, liver damage, opportunistic infection, co-infection, rose (Rosa canina), Juniper berries (Juniperus communis), weight loss, and lung lesion. Barberry roots (Berberis vulgaris), Chicory roots (Cichorium 8. The method of claim 5 wherein the plant material or intybus), Coriander seeds (Coriandrum sativum), Maize extract thereof modulates the immune response. cores with Stigmas (Zea mays). Aronia berries (Aronia mel 9. The method of claim 5 wherein the extract is an alcohol anocarpa), Wild strawberry leaves (Fragaria vesca), Greater Water eXtract. celandine (Chelidonium majus), and Immortelle (Helichrysi 10. The method of claim 5 wherein the extract is an alco arenarii). 5. A method of treating a subject having an infectious hol-water extract formulated as an oral tablet or pill. disease comprising administering a composition comprising 11. A method of reducing adverse effects of chemotherapy plant material, or an extract thereof, or a combination of in a Subject in need thereof comprising administering a com extracts thereof, wherein said plant material is selected from position comprising plant material or extracts thereof or a the group consisting of Inula sp., Foeniculum sp., Juniperus combination of extracts thereof, wherein the plant material sp., Glycyrrhiza sp., Oreganum sp., Calendula sp., Rosa sp., comprises Inula sp., Foeniculum sp., Juniperus sp., Glycyr and Thymus sp., whereby liver function or incidence of rhiza sp., Oreganum sp., Calendula sp., Rosa sp., or Thymus adverse events is improved. sp., or a combination thereof. 6. The method of claim 5 wherein said plant material fur ther contains Aloe (Aloe arborescens), Common knotgrass c c c c c