[0001] This application claims priority to India application Serial Nos. 653/MUM/2000 and 654/MUM/2000, both filed Jul. 14, 2000 and PCT application PCT/IN01/00132, filed Jul. 04, 2001, International Publication Number WO 02/05830 A2, which are incorporated herein by reference in their entirety.
[0002] Introduction
[0003] The use of plants and herbs for general welfare and effectively treating a variety of conditions and ailments dates back to ancient times. Use of a variety of all other type of materials of biological origin (biomass), both prokaryotes and eukaryotes, has also been known for treating a variety of conditions and ailments. The biomass source materials can be from bacteria, fungi, mushroom, yeast, poultry, birds, marine, amphibian, animal and human products.
[0004] However, using these materials of biological origin can also be dangerous because of endogenous toxins. Effective doses are often achieved when large volumes of these materials are used, thus aggravating toxic effects.
[0005] The plants of different genera and species of the Crassulaceae family have been used to combat inflammation, promote healing, and improve overall well being. The Crassulaceae fix carbon via Crassulacean Acid Metabolism (CAM)—in the dark. CAM, so called because originally found in the Crassulaceae family (stonecrops, comprising mostly succulents such as cacti), plants temporally separate the two pathways of carbon fixation, C
[0006] CAM plants are adapted to high stress conditions such as arid zones, including hot and cold deserts, and high altitudes. CAM plants can be found in many genera and are not limited to succulents; these include Kalanchoe, Bryophyllum, Sedum, Sempervium, Rhodiola, Crassulaceae, Aloe, and Cissus sp. CAM plants have been used for many human applications. Most often, plant parts, such as leaves, or plant juices are orally administered. However, the typical dosage is very high, above 100 mg/kg body weight per day (Blazovics et al., 1993; Boikova and Akulova, 1995; Botha et al., 1997; Da Silva et al., 1995; Da Silva et al., 1999; Lans and Brown, 1998; Nadkarni, 1982; Nassis et al., 1992; Obaseiki-Ebor, 1985; Pal et al., 1992; Sendl et al., 1993; Verma et al., 1986; Yoshikawa et al., 1997). Whenever fresh juice or decoction of a particular plant is given internally according to traditional or folk medicine, the useful medicinal agent is believed to be released in the juice from ground leaves, or the decoction of other plant parts; the plant residues remaining after extraction were not added to the composition.
[0007] Kalanchoe is perhaps the most widely known genus in folk medicine.
[0008] Sedum and Sempervivum are more commonly known in folk medicine of Europe whereas Rhodiola and other genera are known more in China and the Far East. Although the uses of these genera are not as far-reaching as that of Kalanchoe, specific uses have been reported, such as for protecting the liver and lowering lipids for Sempervivum which are not reported so far for Kalanchoe.
[0009] Aloe sp. has been used to promote health worldwide for thousands of years.
[0010] The effective dosage for Aloe preparations required is typical for many herbal reparations. Dosage is high: an oral dose of 100 mg/kg per day in animal studies or wound healing (Davies et al., 1989) and 150 mg/kg per day has been prescribed to treat arthritis (Davies et al., 1992). For humans, the reported dose of the extract or juice ranges from 2 g/day (½ teaspoon) to over 100 g/day. Direct topical application also requires several grams per application. Anthraquinones and other low molecular weight compounds in Aloe are also reported to have cytotoxicity (Avila et al., 1997; Mueller and Stopper, 1999).
[0011]
[0012] Most parts of the plant have been used, including the stem, leaves, and tender shoots. In addition, the entire plant, dried, is used in Arabic countries as a “Cure-All” medicine. Pastes made from leaves, stem or entire plants have been used for external applications.
[0013] The dosage levels required are typical for many herbal preparations. Oral dose of juice is 10 to 20 grams/day. Typical dosages of dry stem powder are 2 to 4 grams. Topical applications in the form of paste of dried parts is usually applied at least 10 grams or more. However, the usefulness of this plant is diminished: the various previously known compositions are reported to have mutagenic (including clastogenic) activity (Balachandran et al., 1991; Sivaswamy et al., 1991).
[0014] Table 1 summarizes the common uses of CAM plants; for a comprehensive review of Bryophyllum, Kalanchoe, Aloe and Cissus regarding uses, see (Nadkarni, 1982; Gogte, 2000).
TABLE 1 CAM plants and their uses Plant Application Reference Anti-inflammatory (Pal et al., 1992) pers; (also known as Anti-bacterial (Obaseiki-Ebor, 1985; Verma et al., 1985) Neurotoxin (animal (Botha et al., 1997) other Kalanchoe sp. husbandry study) Anti-parasite (e.g. (Da Silva et al., Leishmania) 1995; Da Silva et al., 1999) Antihistamine (anti- (Nassis et al., 1992) inflammatory) Pharmaceutical (Verma et al., 1986) (general) Sempervivum sp. Lipid reduction (Blazovics et al., (circulation) 1993) Sedum sp. Anti-inflammatory (Sendl et al., 1993) Antihistamine (anti- (Yoshikawa et al., inflammatory) 1997) Aloe sp. Macrophage (Djeraba and Quere, activation 2000) Wound healing, (Davies et al., 1989; circulation Paturmaj, 2000) Immunoregulation (Qiu et al., 2000) General (reviews) (Reynolds and Dweck, 1999; Vogler and Ernst, 1999) Inflammation (Davies et al., 1992) Anti-fungal (Ali et al., 1999) Toxicity (Avila et al., 1997; Mueller and Stopper, 1999) Cissus sp. Animal health (Barakat et al., (general) 1985) Animal health- (Hifny et al., 1984) nervous system (brain) Fracture healing (Chopra et al., 1975; Chopra et al., 1976) Toxicity (Balachandran et al., 1991; Sivaswamy et al., 1991) General Crassulaceae Ovulation regulation (Boikova and references Akulova, 1995) Uses in poultry (Lans and Brown, 1998)
[0015] Many other plants front different families and genera have also been used for the treatment of a wide variety of conditions and ailments all over the world. This range includes:
[0016] Angiosperm-Monocotyledon Plants
[0017] Angiosperm-Dicotyledon Plants
[0018] Gymnosperm Plants
[0019] Many parts of the plants have been used, including the stem, leaves, rhizomes, seeds, tender shoots. In addition, the entire plant, dried, is also used in some cases. Pastes made from leaves, stem or entire plants have been used for external applications.
[0020] The dosage levels required are typical for many herbal preparations. Oral dose of juice or decoction of plant parts is 2 to 50 ml/day. Typical dosages of dry powder are 1 to 4 grams. Topical applications in the form of paste of dried parts is usually applied at least 10 grams or more.
[0021] A few illustrative examples are described. For a comprehensive review regarding human dosage and uses, see (Nadkarni, 1982; Gogte, 2000). For typical human dosage, see Tables 1A, 1B and 1C.
[0022] Angiosperm-Monocotyledon Plants
[0023]
[0024]
[0025]
[0026]
[0027]
[0028] Curcuma genus contains a number of species of medicinal importance such as
[0029] Zingiber genus contains a number of species of medicinal importance.
[0030] The effective dose required is quite high. In animal studies, aqueous decoctions and ethanolic extracts are used. Oral dose of 50 mg/kg per day for anti-ulcer (Agarwal et al. 2000), 100 mg/kg per day for antioxidant enzyme protection (Ahmed et al., 2000), 200 mg/kg per day for lipid lowering (Bhandari et al., 1998), 500 mg/kg per day for gastroprotection (Al-Yahya et al., 1989) and 100 mg/Kg per day for antifilarial (Datta et al., 1987) was used. For humans, the dose of rhizome powder is from 0.75 to 1.5 g/day (½ teaspoon juice).
[0031] Crop health applications of
[0032] The dosage requirements for isolated/derived compounds are quite high. The maximum EC50 activity reported for any compound as IGR is 3.55 mg/ml and as antifungal is 86.46 mg/liter (Agarwal M. et al., 2000).
[0033] Table 1A summarizes the common uses and typical human dosage of a variety of Angiosperm-Monocotyledon plants; for a comprehensive review regarding human dosage and uses, see (Nadkarni, 1982; Gogte, 2000; and the references given below).
TABLE 1A Other Angiosperm - Monocotyledon plants, their uses and human dosage Plant - Angiosperm - Monocotyledon Application Reference Family - Cyperaceae Antimalarial (Thebtaranonth et al., 1995; Weenan et al., Human Dose - Root 1990) Powder 1 to 3 gm per day Anti-inflammatory, (Gupta et al., 1971) anti-pyretic, analgesic Inhibition of Nitric (Seo et al., 2001) Oxide and Superoxide production Family - Gramineae Avoids burning (Nadkarni 1982; micturation and Gogte, 2000) Retz. dysurea, Anti- pyretic Human Dose - Root powder 3 to 6 gm per day Family - Gramineae Lowers LDL and (Nadkarni 1982; Increases HDL Gogte, 2000) Human Dose - Oat Bran 5 to 20 gm per day Family - Gramineae Phagocytosis (Stoika et al., 2001) promoter Human Dose - Seeds 10 to 100 gm per day Family - Liliaceae, Stimulant, Anti- (Nadkarni 1982; Allium sp. Human Dose - pyretic, Gogte, 2000) Diaphoretic, Skin, Bud Paste Anti-inflammatory 1 to 6 gm per day Arthritis, Sciatica, (Nadkarni, 1982; powder: 1 to 3 gm per day Digestion, Tonic Gogte, 2000) Family - Liliaceae Galactogouge, (Nadkarni, 1982; Aphrodisiac, Gogte, 2000) Willd. Human Dose - Tuber Alleviates bleeding powder 3-6 gm per day disorders Family - Zingiberaceae Skin disease, (Nadkarni, 1982; Itching, sprains Gogte, 2000) Human Dose - Rhizome Anti-fungal (Ghosh et al., 1980) Powder 1 to 3 gm per day Family - Zingiberaceae Anti-inflammatory, (Nadkarni, 1982; Analgesic, Gogte, 2000 Human Dose - Rhizome Chologouge Powder 1 to 3 gm per day Family - Zingiberaceae Anti-ulcer (Agarwal et al., 2000) Antioxidant (Ahmed et al., 2000) Human/Animal Health protection Human Dose - Rhizome Humoral Immunity (Puri et al., 2000) Powder (Juice): 0.75 to Lipid Lowering (Bhandari et al., 1998) 1.5 gm (2-4 ml) per day. Skin Tumor (Katiyar et al., 1996) Rheumatism (Srivastava et al., Health 1992) Gastroprotective (Al-Yahya et al., 1989) Antifilarial (Datta et al., 1987) IGR, Antifeedant, (Agarwal M. et al., Antifungal 2001) Fusarium wilt (Singh R. et al., 2000) Molluscicidal (Singh K. et al., 2000)
[0034] Angiosperm-Dicotyledon Plants
[0035]
[0036] The family Apocynaceae has several genera of medicinal importance such as Holarrhena, Rauwolia and Vinca.
[0037] Holarrrhena genus has several medicinally active species.
[0038] Total alkaloids from
[0039]
[0040]
[0041] The family Asclepiadaceae has several genera of medicinal importance such as Hemidesmus and Gymnema.
[0042]
[0043]
[0044] Swertia genus has several medicinally active species.
[0045] Methanolic extracts of whole dried plants are reported to have tyrosinase and PEP inhibitory (Khanom et al., 2000) activity. Methanolic extract at a dose of 100 mg/kg i.p. given to rats was found to be hepatoprotective (Karan et al., 1999). The ethanolic extract given to rats was found to have protective effect against ulcerogenic agents.
[0046] Plyllanthus genus has several plants of medicinal importance. Among these,
[0047] A review of the genus Phyllanthus (Calixto et al., 1998) is available. Hyaluronidase inhibitory activity (Ishizaki et al., 1999) and superoxide scavenging and prolyl endopeptidase inhibitory activities (Khanom et al., 2000) of
[0048]
[0049] The regular usage of seeds in the diet (25 to 50 gm per day) can lower cholesterol and post-prandial sugar (Cunnane et al., 1993; Harris, 1997). The seeds are also a strong regulator of inflammatory mediators and alleviate conditions such as eczema, psoriasis and arthritis (James et al., 2000).
[0050]
[0051] Crop applications of leaves, bark and oil include anti-feedant, IGR, anti-fungal, and anti-nematocidal. Neem cake can be used as a molluscicide (Singh K. et al., 1996). Use of cake mixed with urea and and germinated barley has been suggested as a slow ammonia release (Virk et al., 1989) product. Application of 500 kg/ha of neem cake powder (Rao et al., 1992) caused a striking reduction in the culicine larvae, a vector for Japanese encephalitis virus, in a rice field.
[0052] Terminalia genus has many species with a wide range of medicinal properties. Some of the most widely used species are
[0053]
[0054] Human dosage is 1 gm of fruit powder per day as a general tonic. For purgation, 10 gm dose is used. Mouthwash with a 10% solution of aqueous extract of
[0055]
[0056] Piper genus has several species of wide ranging medeicinal properties.
[0057]
[0058] Administration of Embelin from
[0059] Human dosage of fruit powder is 1 to gm per day. For use against worms, a dose of 10 gm is used. Daily subcutaneous administration of embelin (Gupta et al., 1989) at a dose of 20 mg/kg body weight to male albino rats revealed an inhibition of sperm count and other fertility parameters. Chicks fed
[0060]
[0061]
[0062]
[0063] Oral administration of Lacrinat (Konovalova et al., 2000) containing liquorice root powder for 1 month markedly increased antioxidant activity of the liver. All crude polysaccharide fractions from the shoot and hairy roots of
[0064] Human dose is 1 to 2 gm of root powder per day. Methanolic extract of
[0065]
[0066] Anti-snake venom (Guerranti et al., 2001) properties of
[0067] Human dose is 3 to gm of seed powder per day. Higher doses are also used. In a clinical study on Parkinson's disease patients, a concoction in cow's milk containing
[0068]
[0069]
[0070] Human dose is 1 to 3 gm of seeds per day. Solvent extracted
[0071]
[0072] Human dose is 3 to 6 gm of seed powder per day. Methanolic extract given to mice produced antidiabetic effect at a dose of 1 gm/kg per day.
[0073]
[0074] Ocimum genus has several important medicinal plants.
[0075]
[0076] As a common dietary item, human dose is 10 to 20 gm per day.
[0077]
[0078]
[0079]
[0080]
[0081] Ficus genus has several plants of medicinal importance.
[0082] The fruit extracts have antitumour activity in the potato disc bioassay and also antibacterial activity (Mousa et al., 1994). These results support the use in respiratory and certain skin disorders. Leucocyanidin derivatives from the bark have antidiabetic activity (Kumar et al., 1989), and they promote hexokinase and HMGCOA reductase levels in tissues.
[0083] Human dose is 50 to 100 ml decoction of the bark or 3 to 6 gm of powder per day. Leucocyanidin derivates (Kumar et al., 1989) give a significant effect at 100 mg/kg body weight.
[0084] Table 1B summarizes the common uses and typical human doses of a variety of other Angiosperm-Dicotyledon plants; for a comprehensive review regarding human dosage and uses, see (Nadkarni, 1982; Gogte, 2000; and references given below).
TABLE 1B Other Angiosperm - Dicotyledon plants, their uses and human dosage Plant - Angiosperm - Dicotyledon Application Reference Family - Cucurbitaceae Diabetes, (Nadkarni, 1982; healing, dysmenorrhoea, Gogte, 2000) Human Dosage - Juice of plant or amenorrhoea, skin fruit 10 to 30 nl per day galactogouge Family - Apocynaceae Antitumor (Loukaci A. et al., 2000; Abreu et al., Human Dosage - Decoction of 1999) Seeds Antileschmania, (Abreu et al., 1999) 0.5 to 1 gm per day antimicrobial Antibacterial, (Chakraborty et al., Antimicrobial 1999; Ahmed et al., 1998) Stimulate phagocytosis (Atal et al., 1986) Hepatotoxicity (Arseculeratne et al., 1981) Family - Apocynaceae Sedative, Lowering of (Nadkarni, 1982; B.P., Promotes Uterine Gogte, 2000) Kurazaa Human Dosage - Root contractions, 0.5 to 3 gm per day Fanily - Apocynaceae Anti-cancer (Nadkarni, 1982; Gogte 2000) Human Dosage - Roots 1 to 3 gm per day Family - Asclepiadaceae Blood purifier, Tonic, (Nadkarni, 1982; Alterative, Gogte, 2000) Human Dosage - Root Bark paste Anti-inflammatory 3 to 6 gm Family - Asclepiadaceae Hepatic stimulant, (Nadkarni, 1982; Anti-diabetic Gogte, 2000) Human Dosage - Leaf powder 1 to 2 gm Family - Gentianaceae Liver Toxicity (Karan et al., 1999; Reen et al., 2001) Human Dosage - Whole Plant Tyrosinase and Prolyl (Khanom et al., 2 to 6 gm per day Endopeptidase April and Sept. Inhibitor 2000) Gastric Ulcer (Rafatullah et al., Protection 1993) Family - Euphorbiaceae General Review (Calixto et al., 1998) Superoxide scavenging (Khanom et al., Human Dosage: Total Plant and PEP Inhibition April 2000) Powder Hyaluronidase (Ishizaki et al., 3 to 6 gm per day Inhibition 1999) Anti-tumor (Sur et al., 1998) Human Dosage - Fruit Anti-viral (Liu et al., 1999) Powder: 3 to 6 gm per day Juice: 12 ml per day Family - Linaceae Cholesterol (Harris, 1997) Post prandial blood (Cunnane et al., Human Dosage - seeds glucose 1993) 5 to 50 gm per day Inflammatory Mediator (James et al., 2000) Production Family - Meliaceae Slow ammonia release (Virk et al., 1989) Molluscicidal (Singh K. et al., Human Dosage - Bark Powder: 1 1996) to 2 gm per day. Leaf Juice: 12 ml Culex Mosquito Larvae (Rao et al., 1992) per day in Rice Fields(vector Cake is not used for humans. for encephalitis virus) Family - Conbretaceae Antimicrobial (Ahmad et al., 1998) Terminalia sp. Gastric Emptying (Tamhane et al., 1997) Anticaries agent (Jagtap et al., 1999) Human Dosage - Fruit Powder HIV Reverse (el-Mekkawy et al., 1 gm per day Transcriptase 1995) 3 to 6 gm for purgation Family - Myrtaceae Diabetes, (Nadkarni, 1982; Liver Funcction Gogte, 2000) Human Dosage - Fruit, Seed, Diarrhoea, Dysentry, Bark, Leaves: Menorrhagia with Juice 12 to 25 ml, Powder 1 to 3 gm bleeding Family - Piperaceae Stimulant for appetite, (Nadkarni, 1982; liver, spleen, nerves Gogte, 2000) Promote bioabsorption Human Dosage - Fruit of other drugs 0.25 to 0.5 gm for P. nigrum cough and asthma 5 to 10 gm for P. longum Family - Myrsinaceae Anti-neoplastic (Chitra et al.) Anti-spermatogenic (Gupta et al., 1989) Human Dosage - Fruit Retinotoxic (Low et al., 1985) 1 to 2 gm per day. 10 gm for worms. Family - Menispermaceae Chronic fevrs, (Nadkarni, 1982; Diabetes, Anti- Gogte, 2000) Meirs. inflammatory, Antacid, Human Dosage - Bark powder Restorative 1 to 3 gm Family - Leguminosae Lactagouge and (Nadkarni, 1982; emengouge, Gogte, 2000) Human Dosage - Seeds aphrodisiac 10 to 20 gm per day Family - Leguminosae Tyrosinase Inhibitor (Khanom et al., Sept. 2000) Human Dosage - Root Powder Macrophage Activation (Nose et al., 1998) 1 to 2 gm per day Anti-inflammatory (Kroes et al., 1997) Antioxidant (Konovalova et al., 2000) Family - Legyminosae Anti-snake venom (Guerranti et al., 2001) Human Dosage - Parkinson's Disease (Nagashayana et al., Seed Powder: 3 to 6 gm per day 2000) Root Extract: 50 to 100 ml per Antidiabetic (Akhtar et al., 1990) day Family - Leguminosae Anti-inflammatory (Nadkarni, 1982; Complexion Promoter Gogte, 2000) Human Dosage - Seeds 5 to 50 gm per day Family - Leguminosae Anti-mosquito (Sagar et al., 1996) Solvent Extracted Cake (Ravi et al., 2000) Human Dosage - As Feed Supplement to Juice of Bark or Leaves: 6-12 ml Lambs per day Seeds: 1 to 3 gm per day Family - Leguminosae Hypoglycaemic (Zia et al., 2001) Trypsin/Chymotrypsin (Weder et al., 1991) Linn. Inhibitor Human Dosage - Seed Powder 2 to 6 gm per day. Family - Santalaceae Burning sensation and (Nadkarni, 1982; thirst, Dermatoses and Gogte, 2000) Human Dosage - Heartwood, Oil Pruritis, purulent Powder 2 to 5 gm, Oil 5 to 20 menstruation drops Family - Labiatae Expectorant, Fever, (Nadkarni, 1982; Cough, Cold, Gogte, 2000) Human Dosage - Juice 10 to ml Diaphoretic, Ringworm Seeds - 1 to 2 teaspoon Family - Pedaliaceae Lactagouge and (Nadkarni, 1982; emenagouge, Gogte, 2000) Human Dosage - Seeds aphrodisiac 10 to 20 gm per day Family - Scrophulariaceae Epilepsy, Depresion, (Nadkarni, 1982; Retardation, Gogte, 2000) Human Dosage - Leaf Juice Cough and Cold 2 teaspoon (10 ml) Family - Solanaceae Aphrodisiac, (Nadkarni, 1982; Immune modulator, Gogte, 2000) Human Dosage - Root Powder Rhematic Arthritis, 5 gm per day Abdominal Pain Family - Umbelliferae Anti-inflammatory, (Nadkarni, 1982; Analgesic, Carminative, Gogte, 2000) Human Dosage - Seeds Antihelminthic, Amenorrhoea, Dysmenorrhoea Family - Umbelliferae Anti-inflammatory, (Nadkarni, 1982; Analgesic, Carminative, Gogte, 2000) Human Dosage - Seeds Antihelminthic, 3 to 6 gm per day Galactogouge Family - Moraceae Antitumor, (Mousa et al., 1994) Antibacterial Human Dosage - Antidiabetic (Kumar et al., 1989) Decoction of Bark: 50 to 100 ml per day. Powder: 3 to 6 gm per day.
[0085] Gymnosperm Plants
[0086] There are three species known by the name Talispatra. They are:
[0087]
[0088] Human dosage powder and oil is 1-3 gm and 1-2 gm, respectively. Overdose causes, diarrhoea, vomiting, paralysis and sensory loss.
[0089] Table 1C summarizes the common uses and typical human doses of a variety of Gymnosperm plants; for a comprehensive review regarding human dosage and uses, see (Nadkarni, 1982; Gogte, 2000; and references given below).
TABLE 1C Gymnosperm plants, their uses and human dosage Plant - Gymnosperm Application Reference Order - Conifereae Anti-tumor (Mantle et al., 2001) Toxicity (Kite et al., 2000) Human Dosage - Leaf powder 0.5 to 1.0 gm per day
[0090] Non-Plant Biomass Sources
[0091] A wide range of many other biomass sources have also been used for the treatment of a wide range of ailments all over the world. This range of biomass includes:
[0092] Microbial, Mycological, Marine, Poultry, Animal and Human.
[0093] The preparations start with many different parts of biomass such as blood, mik, urine, organ meat, cartilage and chitin, skin. Total cell mass may also be used. As many of these are food materials, typical human dosage levels required on the basis of fresh part is 10 to 50 gm per day. In the case of dry powders of mushroom, yeast or lactobacilli, the dosage may be 1 to 10 gm.
[0094] The total list of non-plant biomass sources used includes the entire set of life forms and is therefore too exhaustive to be cited here. General use and nutritional applications of meat, milk and eggs from poultry, seafood and animals are also well known and are not repeated here. Only a few illustrative examples of non-plant biologicals are described.
[0095] Mushrooms have been used medicinally for centuries, particularly in traditional Chinese and Japanese medicine (Lombardi R. M. 2002). They are considered as promoters of health and vitality and are adaptogens. The constituents show, immunomodulatory, amtobacterial, antiviral, antitumour, antiparasitic, cardiovascular hypercholesteromiac properties. Active substances include beta-glucans and polysaccharide-protein complexes Button mushroom (
[0096] Beta-glucans are also isolated from the cell walls of yeast (Bacon et al. 1969) and oat and barley bran. Beta-glucans activate the anti-infection and antitumour activity of macrophages. Hence, yeast and oat and barley bran also have immune modulating activities. Beta-glucan dose is typically 2 mg/kg per day.
[0097] Shrimp(Prawn) outer shell and shark fin are used as a source of glucosamine and chondroitin in commercial preparations and are given internally for rebuilding cartilage in joints. No specific medicinal activity has been claimed for them.
[0098] Table 1D summarizes the common uses and typical human dose of a variety of non-plant biomass.
TABLE 1D Non-plant Biomass Sources, their uses and human dosage Biomass Source Application Reference Yeast Digestion, Bacon et al. 1969 Active dried Baker's Yeast Immunomodulation Human Dosage - dry powder 2 to 6 gm Beta-glucan - 200 mg Mushroom Immunomodulation, Lombardi, 2001 Digestion, Blood Mushroom) Pressure Lowering Human Dosage - dry powder 2 to 6 gm Beta-glucan 200 mg Prawn (Shrimp) Source for glucosamine Shark cartillage Source for chondroitin
[0099] Toxicity
[0100] Because of the relatively high effective doses and the traditional methods of preparation, toxins from CAM plants that might be otherwise negligible can adversely affect a subject. For example, Crassulaceae juices and aqueous extracts from various plants have cytotoxic substances (Avila et al., 1997; Balachandran et al., 1991; Botha et al., 1997; Mueller and Stopper, 1999; Sivaswamy et al., 1991). High therapeutic doses of leaf juice for internal use (more than 100 mg/kg bbody weight daily) coupled with high mammalian toxicity close to the habitual level of use (LD
[0101] Toxicity issues rendering compositions less useful is not restricted to CAM plants. Many other plants and other biologicals also have toxic substances and their toxic effects are known. As an example,
[0102] Shelf Life and Potency
[0103] The traditional methods of preparation, juice extraction and ground leaf, suffer from poor shelf life, especially fresh plant juice, which ferments readily if not sterilized or stored properly. Even when dry leaf or stem powder is used, the shelf life of such products is 6 months to one year. Because preparation methods have not been optimized, potency varies by preparation, and thus each preparation may have different effective doses.
[0104] Previous Oil Extraction Methods
[0105] Medicated oils using herbal materials are known in Indian traditional medicine. The base oils used for such preparations are sesame oil and ghee (clarified butter). In South Indian practice coconut oil may replace sesame oil. Sharangdharsamhita, an ancient treatise by Sharangdharacharya (1961), a standard reference treatise of traditional medicine describes a standard method of preparing such “medicated oils.”
[0106] In traditional practice, such extracts are made by boiling together a mixture of kalka (ground paste or homogenate), oil and other liquid substances. The recommended ratio of kalka:oil:liquid substances changes with the nature of liquid substance used. Water, plant derived liquids and juices are the three types of liquid substance described. Plant derived liquids used for making oil extracts are decoctions of plant parts in water. The decoctions are the filtrates prepared by boiling plant part in water, and filtering to obtain a clear liquid or decoction. The ratios of kalka:oil:liquid substance for these three cases are 1:4:16; 1:6:24; and 1:8:32, respectively. Therefore, in these three cases the overall ratio of water to kalka, plant derived liquids to kalka and juice to kalka are recommended to be 16:1, 24:1 and 32:1.
[0107] Juice based or decoction based preparation is the commonly used preparation in practice for fresh or dried succulents. Thus, the standard preparations for succulents call for a very high ratio of juice to ground paste (32:1) or decoction to ground paste (24:1) in making the medicated oil extracts. Traditionally, the effective substances were thought to be present only in the fresh juice or decoction; the bulky residue from ground paste was considered unimportant. Furthermore, the typical recommended dose of such medicated oils is as high as 4 tola (1 tola=11.4 g). This standard procedure is practiced in Ayurveda, the traditional medicine of India. These oil preparations are thus characterized by predominant use of juice or decoction and a high dose. Classical treatises and other references specify particular plants for such methods since the belief is that the various healing substances are liberated from the plants in very specific ways (Nanal, 1995).
[0108] However, Nanal (1995), in reviewing the use of Kalanchoe in the context of theory and practice, remarks that Parnabeeja (Kalanchoe) is not mentioned in any Ayurvedic texts. Nanal mentions several different preparations from Kalanchoe that includes oils, both in sesame and in clarified butter, but does not specify the usefulness of such preparations, and he does not recommend dosages. Such Kalanchoe preparations are usually prepared from the juice of the plant; with only a small amount of leafy residue. These juice-based preparations are seldom used because of serious toxic side effects at very low doses, and when used, are only topically (as opposed to internally) administered.
[0109] Aloe extracts are used commercially in hair oils, often as part of multi-herb medicated oils. Such preparations use extracts prepared from fresh Aloe juice or decoctions of dried Aloe pulp. Aloe oils, by themselves, are not generally recommended for topical or internal use; instead, Aloe liquids, gels or pulp are used.
[0110] The use of oil extracts of Cissus is unknown.
[0111] In a more general way, oil or ghee (clarified butter) extracts of plants are more commonly used in multi-herb compositions used for both external and internal applications. Specific detailed description for individual plants is difficult to come by. The generalized procedures described above are therefore the guidelines to go by.
[0112] Oil extract preparations for non-herbal biomass are not described in traditional medicine.
[0113] The use of paste or residue of total plant or plant parts as the predominant component compared to the use of juice or decoction as the dominant component in extractions is contrary to the teachings of traditional medicine. However, surprisingly, the methods of the invention allow for the preparation of compositions that have an enormous potential to improve health by mining the beneficial effects and minimizing toxicity of plants. These methods also produce compositions of high potency at very low doses, thus further reducing any potential for toxicity.
[0114] The methods of this invention also produce compositions of high potency and low toxicity from all non-herbal biomass sources including microbial, mycological, veterinary, human and aquatic.
[0115] The invention circumvents the problems of toxicity and shelf life by providing a general way to make compositions that incorporate oil extracts of a wide variety of plants and other non-plant biomass. These compositions have a very high useful activity (on the basis of biomass material dose) which allows extremely low dosage and as a result, the toxicity is considerably reduced. These compositions bring out the activity characteristic of each biomass. As a result, these compositions are useful for a wide variety of applications, including human, veterinary and plant applications, for both known and novel uses. These applications include broad general effects such as disease resistance, stress resistance, general promotion in health and growth, delaying senescence and special effects such as wound healing, skin repair, stimulation of hair growth, bone repair and lipid lowering.
[0116] This invention relates to compositions comprising biomass extracts to be used in human, veterinary and agricultural aquatic, mycological and microbial applications.
[0117] The novel compositions are prepared from biomass by taking the entire biomass or appropriate parts, washing them with water, soaking them (in case of hard seeds or dry material), pounding them (in case of hard materials such as seeds), or cutting them into pieces (in case of soft plant material), mixing them with water, homogenizing the mixture, and filtering the homogenate to obtain two fractions: juice (J) fraction (as the filtrate) and the leafy residue (or stem, biomass part, etc.; LR) fraction. The fractions may be mixed together, or kept separate as J or LR fractions. The total homogenate or any form and any proportion of the fractions may be mixed with oil or fat, adding water, bringing the mixture to boil, stirring the mixture to provide good contact of biomass with both water and oil and to minimize sticking of biomass to the vessel bottom, removing the water by boiling, cooling the mixture, and filtering the mixture to separate the oil extract from the residue, which are referred to as the first oil extract and first residue, respectively. A second extract from the particular fraction may be obtained by washing the corresponding first residue with oil and filtering to obtain a second extract. Subsequently, the first and second extracts may be combined. The composition can be used to treat a variety of human and animal ailments, and has manifold applications in agriculture, using exceptionally low doses and without toxic side effects. These uses will become apparent as the various embodiments of the invention are discussed.
[0118] The novel herbal compositions of the invention, is prepared by a method wherein the total biomass or one or more biomass parts are first reduced in size by soaking, pounding and cutting as required, and are then homogenized, adding water as required. The total homogenate (kalka) is filtered to separate the juice fraction (J) from the concentrated stem/leaf/plant parts residue (LR). The total homogenate may be added or the two fractions may be added separately (mixed in any proportion) to oil with additional water as required; the water is then removed by boiling. Stirring is provided to promote good contact between the biomass, oil and water.
[0119] Total biomass or any part or parts of the biomass can be used to prepare a range of extracts. The concentrated seed/rhizome/stem/leaf/biomass parts residue may be used to prepare LR fraction; or, only the juice fraction may be used to obtain J fraction. Thus, the proportion of the biomass residue fraction to the juice fraction may be 1:0 or 0:1. The combined extract comprises both the J and LR fractions. By varying the starting biomass materials (including plant, non-plant materials and their parts, etc.), the admixing of J and LR fractions, and filtration provides the preparation of extracts with a variable biological activity that are suitable for specific applications (see Examples). Because various factors can be adjusted during the preparation of the compositions of the invention (biomass parts, ratio of leaf, stem, biomass parts, J fraction, LR fraction, oil, etc.), the drawbacks of traditional methods of preparation, such as cytotoxicity and excessively high doses, are circumvented.
[0120] In addition, the compositions of the invention have unexpected and useful results, including high potency coupled with low toxicity, an exceptionally long shelf life, and a wide range of usefulness.
[0121] The two important features of this invention in the context of plant extracts are the ratio of oil to homogenate or kalka of biomass/biomass parts and the ratio of liquid substances to homogenate or kalka of biomass/biomass parts taken for boiling.
[0122] The traditional methods recommend an oil to kalka ratio of 4:1, 6:1 and 8:1 for use depending upon the use of water, plant decoction or juice as the liquid substance used. This invention uses the lowest possible ratio consistent with ease of processing. Thus, with succulent leaves and fruit as the plant part, the typical ratio of oil to starting plant part is 1 to 2 in the presence of water. A ratio of homogenate to the oil of 0.1 to 1.5 can also be used. In the case of dried material and particularly where the material forms a pasty mass after homogenization, oil to starting plant part ratio of 4:1 may be used in the presence of water.
[0123] The traditional methods recommend the overall ratio of water to kalka, plant derived liquids to kalka and juice to kalka to be 16:1, 24:1 and 32:1, respectively.
[0124] This invention uses ratios which are significantly different. In general, present invention uses overall ratio of water to kalka, plant derived liquigds to kalka and juice to kalka less than 16:1, less than 24:1 and less than 32:1, respectively. This is best understood in the context of one of three cases.
[0125] The first case is where the total homogenate is used for boiling without separating the LR and J fractions. In this case, unlike the traditional method, there is no additional decoction or juice is used at all. Thus, it is equivalent to using a ratio of decoction or juice to kalka or homogenate of zero instead of 16:1 and 24:1 and 32:1.
[0126] The second case is where the LR fraction is taken further for boiling. In this case, not only no additional decoction or juice is used but most of the juice inherently present in the succulent starting material is also washed away. Thus, this method is equivalent to having a negative ratio of juice to initial plant material.
[0127] In both these cases, some water inevitably gets added for homogenization and also to control the time of boiling. The total water to initial plant material is typically in the ratio of 1:1 to 8:1. The low ratio is likely to be used with succulents where total homogenate is being used. The higher ratio is required when starting with dry materials which tend to form a thick paste. Even the higher ratio is much lower than the 16:1 ratio recommended in traditional literature.
[0128] Thus, for total homogenate or for the LR fraction, considerably lower total liquid quantities are used. This drastically cuts down the processing time, avoiding loss of activity caused by excessive heating for a long time. At the same time, this still provides an ability to adjust the ratio of water and helps in controlling and optimizing the boiling time to the desired level as required for each specific extract.
[0129] This invention also incorporates another novel feature as an “Extraction Concept.” Traditionally, plants are typically extracted in one solvent. The filtrate is then concentrated and evaporated to dryness to obtain the active concentrate. U.S. Pat. No. 5,529,778 (1996) describes a composition made by such a process where the plant material is extracted in distilled water and the filtrate is evaporated to dryness. Sometimes, the residue from the first solvent extraction may be further extracted by a series of different solvents, all the filtrates combined together and then evaporated to obtain the active material. In some other cases, the plant is extracted in one solvent and then the filtrate is back-extracted into another solvent.
[0130] However, the concept of fractionating the total homogenate into LR and J fractions and separately processing them in oil to produce two separate compositions with widely different biological activity is novel and forms a special feature of this invention. This can be explained in the following manner. The step of homogenization brings the plant material with intimate contact with a solvent (e.g. cold water). After filtration, the two fractions, LR and J, contain a selective fractionation of plant components in them. Subsequent oil extraction, therefore, yields two separate extracts with widely differing biological activity in many cases. In some cases one fraction gets enhanced activity and reduced toxicity than the total homogenate for a particular application. In some other cases, one of the fractions becomes stronger in one activity while the other fraction also develops strong activity for a different application. Thus, this scheme of fractionation/extraction provides a general method to greatly enhance the utility of many extracts and therefore the utility of many plants as per this invention. In the oil extract of the present invention, the ratio of the first residue to the oil may be from 0.05:0.5. Alternatively, in the oil extract of the present invention, the ratio of the biomass juice to the oil may be 0.5 to 10.
[0131] The key features, methods and the ‘Extraction Concept’ outlined above are also applicable to making compositions from all non-plant biomass materials as per this invention.
[0132] Potency
[0133] Doses of less than 1 mg/kg body weight/day on the basis of total fresh leaf or stem or plant parts or non-plant biomass weight for human (and mammalian) internal use is sufficient to produce significant therapeutic effects compared to greater than 50 mg/kg body weight therapeutic dosage traditionally used. A 5 to 50 mg plant or other biological material equivalent is sufficient for topical applications, compared to the traditional use of 5 to 10 g of juice or homogenate. A dose level of less than 1 mg/kg body weight per day of plant equivalent is effective in poultry applications, compared to approximately 100 mg/kg body weight per day as traditionally used.
[0134] Low Toxicity
[0135] Oil extracts of
[0136] Similar enhancement in the efficacy/toxicity ratio is expected for other plants and non-plant biologicals as well.
[0137] Shelf Life
[0138] Fresh juice or extracts prepared by traditional methods ferments rapidly. However, the compositions of the invention remain potent much longer. In case of Crassulaceae, the extracts have remained potent even after at least 7 years.
[0139] A. Human
[0140] The compositions of this invention can be made from a wide variety of plants and non-plant biomass. For each biomass, the key activities as reported in the literature can be incorporated in the compositions of this invention. Hence, the compositions of this invention have a wide variety of human applications. An illustrative summary of examples of the many embodiments for selected CAM plants is given in Table 2.
[0141] Thus, in the context of CAM plants alone, the compositions of the invention may be used to treat respiratory disorders and skin conditions, modulate the immune system, lower blood lipid levels, improve digestion, promote healing, regulate menstruation and ovulation, and may be used as an anti-inflammatory agent. Dosages are unexpectedly low when compared to traditional applications, from 100 to 1000 times less.
[0142] The compositions may also be used prophylactically.
TABLE 2 Human embodiments of uses for the compositions of the invention General embodiment Specific embodiments Respiratory Treating coughs, colds and congestion Treating asthma, including allergy and stress-induced Circulatory Promoting circulation in feet Lowering low density lipoproteins (LDL)/cholesterol Lowering triglycerides Digestive Treating ulcers from Diabetes Reducing stomach acidity Reducing stomach upsets Promoting appetite Growth Promoting weight gain Promoting height growth in children Healing/Wound Promoting healing of bruises and cuts repair Promoting healing of ulcers from leprosy Promoting healing of bedsores Promoting healing of burns Promoting healing of piles (hemorrhoidal tumors) Treating fistulas Stress and energy Promoting sound sleep levels Promoting lowered stress and tension Promoting higher energy level in elderly Inflammation Reducing general pain and swelling Treating spondylitis (inflammation of the vertebrae) Treating arthritis Treating gingivitis Treating toothaches Reproduction Treating oligospermia Promoting sperm motility Regulating ovulation Regulating menstruation Managing menstruation pain Treating irregular, especially prolonged (menorrhagia), menses Dermatology Treating pimples Treating sunburn and tan Treating lichenplanus Treating hyperpigmentation Treating eczema/dermatitis Treating psoriasis Preventing hair loss Promoting hair growth Vision Promoting vision recover after macular surgery Treating dry cornea Treating styes
[0143] Utility of the compositions of this invention are not restricted to the embodiments listed in Table 2. Innumerable other embodiments for particular plant and non-plant biomass are possible as the invention is applicable to a wide variety of plant and non-plant biomass. The range of embodiments can be further increased by using appropriate mixtures of biomass. A few illustrative examples of such applications are given below:
[0144] reduce sciatica pain,
[0145] improve handgrip post paralytic stroke,
[0146] restore ‘Foot Drop’ condition post viral polyneuritis attack,
[0147] restore concentration and memory post brain haemorrage,
[0148] alleviate colitis,
[0149] reduce hyperpigmentation,
[0150] regulate sugar om blood and
[0151] alleviate headache.
[0152] B. Veterinary
[0153] The compositions of the invention may also be used to improve livestock productivity, treat animals for a variety of conditions, and improve animal health. Additionally, other benefits may be realized, such as an early onset of maturity, improvement in the shelf life of buffalo milk, an improvement in feed conversion efficiency (more production for less feed), and a decrease in mortality. Table 3 summarizes examples of embodiments with CAM plants in which the compositions of the invention may be used on animals. Utility of the compositions of this invention are not restricted to the embodiments listed in Table 3. Innumerable other embodiments for particular biomass are possible as the invention is applicable to a wide variety of plant and non-plant biomass.
TABLE 3 Veterinary embodiments of uses for the compositions of the invention General embodiment Specific embodiments Growth Increasing weight gain Increasing growth rate Decreasing mortality (overall improving health) Hastening maturity Productivity Increasing egg laying with less feed (egg-laying birds) Improving quality of milk (buffalo)
[0154] C. Agricultural
[0155] The utility of the compositions, of the present invention extends to all areas of the Plant Kingdom. For example, the compositions of the invention have beneficial effects on vegetables, ornamentals, flowers, fruits, trees, cereals, legumes, herbs and medicinal plants. Table 4 summarizes examples of embodiments in which the compositions of the invention may be used in plants. The utility of the compositions of this invention are not restricted to the embodiments listed in Table 4. Innumerable other embodiments for particular biomass are possible as the invention is applicable to a wide variety of plants.
TABLE 4 Embodiments of uses for the compositions of the invention General embodiment Specific embodiments Germination Promoting vigorous rooting and shooting and germination vigour Vegetative growth Promoting branching Promoting growth (especially height) Leaf production Promoting increased chlorophyll levels Promoting larger leaves and more leaf area per plant Promoting higher carbohydrate content Promoting higher number of leaf active days (LAD) Extending leaf life Delaying senescence Flowering Promoting early onset Reducing flower drop Promoting larger bloom size Promoting uniform bloom size Increasing production Fruit Reducing fruit drop Promoting larger sized fruits Promoting fruit appearance (e.g. “shine”) Promoting production Productivity Promoting increased yields, whether fruit, flower, or vegetable Increasing primary metabolites (e.g., sugars, proteins, and oil content) Increasing secondary metabolites (e.g., anti-oxidants, aromatics, and medicinal substances) Herbicide Eliminating unwanted plants/grasses Controlling growth of plants/grasses Acting as a synergist with pre-emergent herbicides Shelf life Promoting shelf life of fruit and flowers Pest defenses Promoting higher levels of defense chemicals (e.g., polyphenols and alkaloids) Reducing damage by pests (e.g., white fly, aphid, jassid, fruit fly, fruit borer, mite, stem borer, millibug) Reducing incidence of viral attacks Reducing incidence of fungal damage Environmental stress Promoting frost resistance Promoting drought tolerance Increasing osmolyte levels (e.g., proline) Allowing co-existence of insects while decreasing insect damage Qualitative Decreasing thorny habits Promoting natural plant colors (e.g., ornamentals) and shiny leaves/fruit
[0156] Other embodiments of the invention will be apparent to those of skill in the art.
[0157] Crassulacean Acid Metabolism (CAM)
[0158] “CAM” involves the use of both the C
[0159] The C
[0160] The C