WO2008136013A1 - Extrait organoleptiquement amélioré de salacia et méthode associée (minora) - Google Patents

Extrait organoleptiquement amélioré de salacia et méthode associée (minora) Download PDF

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Publication number
WO2008136013A1
WO2008136013A1 PCT/IN2007/000263 IN2007000263W WO2008136013A1 WO 2008136013 A1 WO2008136013 A1 WO 2008136013A1 IN 2007000263 W IN2007000263 W IN 2007000263W WO 2008136013 A1 WO2008136013 A1 WO 2008136013A1
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Prior art keywords
extract
diabetic
salacia
agents
plant
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PCT/IN2007/000263
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English (en)
Inventor
Villoo Morawala-Patell
Rajesh Ullanat
Ashok Mundrigi
Jagadeesh Badamaranahalli Henjarappa
Chandramohan Bangalore Siddaiah
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Avesthagen Limited
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Publication of WO2008136013A1 publication Critical patent/WO2008136013A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/37—Celastraceae (Staff-tree or Bittersweet family), e.g. tripterygium or spindletree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to clinically safe and non-toxic plant extracts useful for the management of diabetes and their related disorders. More particularly, the present invention relates to easily oral administrable bioactive Salacia oblonga extracts with an improved efficacy for the management of diabetes and related disorders. The invention also discloses bioactive Salacia extracts with improved organoleptic properties. The invention further discloses oral administrable bioactive salacia extracts, which can be safely given to both children and adults having blood glucose intolerance.
  • the invention discloses a process for the preparation of bioactive salacia extracts that are non-toxic, clinically viable, have a better and improved taste appeal and those, which may be effectively used for the management of early and mid diabetes and related disorders.
  • Diabetes mellitus commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood (hyperglycaemia).
  • blood glucose levels are tightly controlled by insulin, a chemical signalling substance (hormone) that is produced by a gland near the stomach called the pancreas.
  • hormone a chemical signalling substance that is produced by a gland near the stomach called the pancreas. Insulin helps lower the blood glucose level and stimulates the body to make use of glucose.
  • insulin is released from the pancreas to normalise the glucose level.
  • the elevated glucose levels will not be normalized easily as compared to healthy individuals. This causes abnormally high levels of blood glucose, which ultimately leads to the presence of glucose in the urine (glucosuria).
  • IDDM insulin-dependent diabetes mellitus
  • NIDDM non-insulin-dependent diabetes mellitus
  • IDDM results from insulin deficiency caused by cell-mediated autoimmune destruction of pancreatic beta cells. and generally develops in the young.
  • IDDM accounts for approximately 10- 15% of the diabetic population worldwide.
  • NIDDM results from a variable combination of insulin resistance and insulin deficiency, which generally noticed in adults above 35 years.
  • NIDDM can be noticed at a younger age too.
  • NIDDM accounts for over 85% of the diabetic population worldwide.
  • Diabetic Neuropathy Diabetic Diarrhea
  • Urinary retention Gustatory Swelling
  • Papillary Reflexes Cardiac Autonomic Disturbances
  • Collagen Disturbances thickening of capillary basement membrane
  • vessel wall matrix increase in vessel wall matrix and cellular proliferation • resulting in vascular complications like lumen narrowing, early atherosclerosis, sclerosis of glomerular capillaries, retinopathy, neuropathy and peripheral vascular insufficiency.
  • Diabetic Neuropathy is the most common and affects patients at earlier stages. As such, there is no drug available for the curing of these diabetes or its complications.
  • Diabetes is a life style disease and can be controlled / managed though not completely cured.
  • therapies for the management of diabetes Firstly, it may be managed with a carbohydrate-based, low-fat diet.
  • the carbohydrates in such a diet inevitably put large amounts of glucose in the bloodstream.
  • the patients therefore need to be administered insulin daily.
  • the drawback associated with this therapy is that the right dosage of insulin needs to be administered every time.
  • a greater than required insulin dosage can reduce the glucose level too much such that it may become risky for the patient.
  • a skilled administrator is therefore a must in following such a therapy.
  • the complications' attached to such a form of therapy makes it tedious and less patient compliant
  • the second method of managing diabetes is by using chemical drugs. Based upon the kinds of diabetes prevalent, the drugs available for treatment can be grouped under the following heads: i. Pancreatic stimulators: - This class of drugs helps to stimulate the pancreas, leading to increased secretion of insulin. This addresses the diabetes caused by inadequate insulin secretion. Common examples of this category are sulphonylureas and meglitinides. ii. Insulin sensitizers: -This category of drugs improves the cell's sensitivity to the presence of insulin, thereby improving the uptake of glucose into the cells, leading to better blood sugar control. The common examples for this category are the biguanides, thiazolidinediones. iii.
  • Alpha-glucosidase inhibitors - Acarbose and meglitol are the commonly known alpha-glucosidase inhibitors. These drugs help the body to lower blood glucose levels by blocking the breakdown of starch and oligosaccharides in the intestine.
  • Insulin -As explained earlier, insulin is exogenously supplemented in the case of people suffering from both type I and type II diabetes.
  • the available synthetic drugs however suffer from concomitant side effects caused due to long duration of usage. It is indicated that cardiovascular mortality is higher in patients with oral hypoglycemic than in those who are treated without them. Sulphonylurcas cause hypoglycemia as a side effect. Biguanides cause lactic acidosis. Oral hypoglycemic drugs also cause GIT irritation, weight gain, hypertension, etc. On continuous and constant exertion, the diabetic person is also liable for pancreatic fatigue. In addition, many of these available drugs lead to drug resistance in patients with long durations of use. Acarbose and meglitol are known to cause gas and diarrhea.
  • the drugs listed above have different mechanisms of action to lower blood glucose levels. They are therefore often prescribed in the form of a combination therapy. More over combination therapy suits best, when one single drug does not seem to show the desired effects. Many combinations are known and used. For example, a biguanide and a sulfonylurea may be used together. Adding a drug from a different category of diabetes therapy is definitely more effective than switching from one single pill to another. Yet the disadvantages associated, with combinatorial effect of taking more than one drug each of which has individual side effect attached to it, cannot be avoided. Besides, taking more than one drug at a time makes the therapy more costly and less patient compliant
  • the ayurvedic and ancient Indian literature refers to the usefulness of many plant extracts in the treatment of diabetes mellitus.
  • the use of traditional medicines, mainly derived from plant sources, has been a major part in the management of many chronic ailments including diabetes.
  • Physicians in India who practice Ayurveda, Unani, and Siddha have long used extracts of leaves, flowers, fruits, seeds, wood, bark, roots, or even whole plants of more than a hundred Indian medicinal plants for the treatment of diabetes.
  • One of the plants actively used in Ayurveda for the treatment of diabetes is Salacia.
  • Salacia Oblonga commonly called “Ponkoranti”
  • Salacia belongs to the family Celastraceae. The roots and stems of this plant arc used for the treatment of diabetes. Salacia has also proven effective against increasing problem of other life stage diseases like hypertension. It has also been found effective in lowering triglyceride and LDL cholesterol levels.
  • Salacia oblonga is known to exhibit alpha glucosidase ativity. It contains two potent ⁇ -Glucosidase inhibitors: Salicinol and Kotalanol. Methanol extracts from the roots of Salacia oblonga exhibit an inhibitory effect on the increase of serum glucose levels in sucrose- and maltose-loaded rats. Salacia oblonga has also been found to show inhibitory activity on Aldose Reductase, which is related to such chronic diabetic complications as peripheral neuropathy, retinopathy, and cataracts.
  • the Applicant has carried studies for amalgam of 15 (fifteen) different traditional Indian medicinal plants' including Salacia and the same is disclosed in the WO publication bearing the number WO/2006/061676.
  • the studies included isolating the actives from Salacia, characterizing the extract, combining with other plant extracts and studying their activity for management of diabetes.
  • the instant invention piovides a process for preparation of organoleptically enhanced Salacia extract which can be used for management of not only diabetes but also all the diabetic related disorders.
  • each herb has properties of " curbing many disorders and this property is attributed to the composite nature of the herbal preparation.
  • the related art of interest describes various processes for obtaining Salacia extract, but none discloses the present invention. There is a need for an effective process in obtaining an organoleptically improved salacia plant extract which is not only safe but also used for management of diabetes and its related disorders. The related art will be discussed in the order of perceived relevance to the present invention.
  • US Patent 6,376,682 relates to compound extracted from salacia oblonga having the characteristic of specifically inhibiting the activity of alpha. -glucosidase (an enzyme that breaks down disaccharidcs, etc.) at the intestinal level. It does not reflect on the additional, insulin mimetic and insulin sensitization activities of found in a well- extracted salacia extract.
  • alpha. -glucosidase an enzyme that breaks down disaccharidcs, etc.
  • US Patent 5,691 ,386 relates to a compound extracted from a woody climbing plant belonging to the Cclastaceac family and inhibits the activity of .alpha. -glucosidase, and further to an antidiabetic and dieting agent containing the compound and a method for producing such a compound. It does not mention any insulin mimetic activity attached to salacia extract. Similarly no insulin sensitization activity of salacia is disclosed in the patent as well.
  • US Patent Application 20020041904 states a compound which is extracted from Salacia oblonga or Salacia prinoides and contains a compound having an alpha.- glucosidasc inhibiting effect. It however does not state the insulin mimetic and insulin sensitization activities of salacia.
  • the invention therefore discloses an extract with acting with a single mode of action.
  • composition for Preventing/Treating Diabetes and Health Food Containing the Active Ingredient Thereof "Composition for Preventing/Treating Diabetes and Health Food Containing the Active Ingredient Thereof " .
  • This citation discusses about the anti-diabetic activity of Salacia extract. However, the same is no where in relation to the application of instant invention, wherein it utilizes a novel and inventive process to obtain a organoleptically improved or enhanced salacia extract.
  • the salacia extract so prepared by making use of the instant invention laid down hereunder has been very surprisingly found to display three modes of action. It not just shows enhanced alpha glucosidase activity but also works equivalent to any well-known insulin sensitizer drugs. f urthermore, the extract has additional insulin mimetic activity and free radical scavenging abilities. It is thus capable of managing blood sugar in diabetes mellitus patients and also lends itself for long-term use without any side effects and without developing resistance. It is therefore the main objective of the invention to provide a safe and efficacious plant extract, which acts upon diabetes by at least three different mechanisms.
  • the principal object of the present invention is to prepare a Salacia plant extract having enhanced organoleptic properties. Yet another object of the present invention is to develop a process for obtaining organoleptically enhanced Salacia plant extract.
  • Still another object of the present invention is to study the activity of the Salacia plant extract for its anti-diabetic, its related disorders and free radical scavenging activity. Still another object of the present invention is to develop a safe, non-toxic and adverse effects free Salacia plant extract. Still another object of the present invention is to provide salacia plant extract capable of treating diabetes in more than one mode of action. Still another object of the present invention is to provide salacia plant extract which is easily and safely administrable to children and adults.
  • the present invention provides an organoleptically enhanced salacia plant extract for management of diabetes and related disorders; a method of treating diabetes and/ or related disorders in a subject in need thereof, said method comprising step of administering pharmaceutically acceptable amount of organoleptically improved salacia plant extract, optionally along with pharmaceutically acceptable additives, to the subject; and a process for enhancing organoleptic and anti diabetic properties of a salacia plant extract, said process comprising steps of (a) size-reducing plant parts to obtain powder; (b) extracting the powder with a solvent and/ or combination of solvents by heating at temperature ranging from 25° to 100° C to obtain a mixture; (c) clarifying the mixture to arrive at clear liquid: (d) concentrating the clear liquid to achieve a concentrated extract; (c) solubilizing the concentrated extract in a solvent and re- concentrating it to obtain further concentrated extract; and (f) treating the further concentrated extract with an organoleptic agent (s) followed by drying the treated extract to obtain organoleptically enhanced salaci
  • Figure 1 is a bar graph showing Insulin Mimetic Activity of Treated Salacia Water Extract in 3 13 L I Cell Lines.
  • Figure 2 is a bar graph showing Insulin Mimetic Activity of Treated Salacia Alcohol Extract in 3T3 Ll Cell Lines.
  • Figure 3 is a bar graph showing the percent insulin Mimetic Activity of Untreated Salacia extract as Determined by 3T3 Ll glucose Uptake Assay
  • Figure 4 is a bar graph showing Insulin Sensitization Activity of Treated Salacia Water Extract in 3T3 LI Cell Lines.
  • Figure 5 is a bar diagram showing is a bar graph showing Insulin Sensitization Activity of Treated Salacia Ethanol Extract in 3T3 LI Cell Lines.
  • Figure 6 is a bar diagram showing percent insulin sensitization activity of salacia water extract in comparison to insulin
  • Figure 7 is a bar graph showing the alpha gliicosidase inhibition potential of salacia water extract.
  • Figure 8 is a bar diagram showing free radical scavenging ability of salacia plant extracts
  • Figure 9 is a bar diagram showing total polyphenol estimation of salacia water extract
  • Figure 10 is a bar graph showing percentage variation of Fasting Blood Glucose (FBG) level over 5 week period in various groups of animals.
  • FBG Fasting Blood Glucose
  • Figure 11 is a bar diagram showing percentage variation in postprandial glucose (PPG) over 5 periods.
  • Figure 12 Percent alpha-glucosidase inhibition of various Salacia extract in comparison to acarbose
  • Figure 13 Percent insulin sensitization activity of different Salacia concentration 334 ⁇ g as determined by 3T3-L1 glucose uptake assay Detailed description of the present invention
  • the present invention is in relation to an organoleptically enhanced salacia plant extract for management of diabetes and related disorders.
  • the organoleptic agents are decolorizing and deodorizing agents.
  • the extract is treated with said organoleptic agents at a ratio ranging from 0.5: 10 to 10: 0.5.
  • the present invention is in relation to a method of treating diabetes and/ or related disorders in a subject in need thereof, said method comprising step of administering pharmaceutically acceptable amount of organoleptically improved salacia plant extract, optionally along with pharmaceutically acceptable additives, to the subject.
  • the subject is an animal or human being.
  • the organoleptically improved salacia plant extract is having insulin mimetic activity, insulin sensitizing activity, and alpha glucosidase activity.
  • organoleptically improved salacia plant extract is administered at dosage ranging between 20 to 300 mg/kg body weight.
  • the organoleptically improved salacia plant extract is administered preferably at dose of about 50mg/kg body weight.
  • the related disorders comprise diabetic acidosis, diabetic xanthoma, diabetic myatrophy, diabetic ketosis, diabetic coma, diabetic stomach disorders, diabetic gangrene, diabetic ulcer, diabetic diarrhea, diabetic microangiopathy, diabetic uterosclerosis, diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, diabetic blister, diabetic cataract, diabetic dermatitis, diabetic scleredema, diabetic retinopathy, diabetic necrobiosis lipoidica and diabetic blood flow obstructions.
  • additives are selected from a group comprising granulating agents, binding agents, lubricating agents, disintegrating agents, sweetening agents, coloring agents, flavoring agents, coating agents, plasticizers, preservatives, suspending agents, emulsifying agents and spheronization agents.
  • the organoleptically improved salacia extract is formulated into dosage forms selected from a group comprising tablet, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion in hard or soft gel capsules, syrups, elixirs, phyotceuticals and neutraceuticals.
  • organoleptically improved salacia plant extract is non-toxic and free of adverse effects.
  • organoleptically improved salacia plant extract can be administered to subjects in combination with agents selected from a group comprising synthetic anti-diabetic drugs, anti-diabetic plant extracts and food stuffs.
  • the present invention is in relation to a process for enhancing organoleptic and anti diabetic properties of a salacia plant extract, said process comprising steps of (a) size- reducing plant parts to obtain powder; (b) extracting the powder with a solvent and/ or combination of solvents by heating at temperature ranging from 25° to 100° C to obtain a mixture; (c) clarifying the mixture to arrive at clear liquid; (d) concentrating the clear liquid to achieve a concentrated extract; (e) solubilizing the concentrated extract in a solvent and re-concentrating it to obtain further concentrated extract; and (f) treating the further concentrated extract with an organoleptic agent (s) followed by drying the treated extract to obtain organoleptically enhanced salacia plant extract.
  • the size reduction is done cither manually or mechanically to achieve powder particle size ranging from 50 # to 200 tl and pi cfcrably of 100 mesh size.
  • the parts of plant are selected from a group comprising root, shoot, leaf and seeds or the whole plant.
  • the solvent used for extraction could be aqueous, organic and/or combinations thereof.
  • said solvents and/ or combination of solvents are selected from a group comprising water, buffer, cell media, dilute acid, dilute bases, methanol, ethanol. n-propanol, isopropanol, 2-butanol. and terbutanol.
  • the powder is extracted with a solvent preferably at a ratio of about 1 : 10.
  • the extraction of powder with solvent and/ or combination of solvents is brought about by stirring for a time period ranging from 2-3 hours.
  • concentration method is selected from a group comprising soxhlation, rotary evaporation, distillation, centrif ugal vacuum evaporation and lyophilisation.
  • solubilization of concentrated extract is carried out in a solvent selected from a group comprising ethyl acetate, diethyl ether, hexane, dichloromethane, butyl alcohol, ether, acetone and/ or combination thereof.
  • a solvent selected from a group comprising ethyl acetate, diethyl ether, hexane, dichloromethane, butyl alcohol, ether, acetone and/ or combination thereof.
  • said organoleptic agents ai c decolorizing and deodorizing agents.
  • the decolorizing agents are selected from a group comprising carbon, activated carbon, resins, chemicals like hydrogen peroxide, acetone peroxide, benzoyl peroxide, sulfites like sodium metabisulfite, ammonium persulfate, sodium hydrosulfite, sodium sulfite and sulfur dioxide.
  • said deodorizing agents are selected from a group comprising activated carbon and hydrogen peroxide.
  • said treated extract is dried at a temperature ranging from 35° to 65° C.
  • said treated extract is preferably dried at a temperature of about 50 C.
  • the extract is treated with said organoleptic agents at a ratio ranging from 0.5: 10 to 10: 0.5. In still another embodiment of the present invention, wherein the extract is treated with said organoleptic agents preferably at a ratio of about 1 : 0.25.
  • the present invention provides a plant extract with ant diabetic activity.
  • the invention provides a salacia plant extract with ant diabetic activity.
  • the invention provides Salacia extract with improved anti diabetic activity and free radical scavenging ability.
  • the invention provides a non-toxic Salacia plant extract with anti diabetic activity.
  • the invention provides a non-toxic salacia plant extract capable of treating diabetes in more than one mode of action. Therefore, the invention provides a non-toxic salacia extract with a better efficacy in the treatment of diabetes mellitus.
  • the invention provides a salacia plant extract which has improved organoleptic properties and which is easily and safely administrable to children and adults.
  • the invention provides a salacia plant extract, which is non-toxic, patient compliant, shows better efficacy and effectively in the treatment of diabetes and exhibits improved organoleptic properties.
  • the invention provides also the method of preparation of a non-toxic, patient compliant, improved and effective salacia plant extract.
  • the crux of the invention lies in the preparation of an extract by a procedure, which enhances both its activity and organoleptic appeal.
  • Plant material suitable for preparation of the plant extract for inclusion of the therapeutic composition of the invention is derived from a potential plant administered to a person suffering from diabetes, which results in the lowering of the blood glucose level of the patient. Administration of the composition to the patient both prevented and treated incidences of clinical diabetes.
  • the potential plant is a member of the family Celastraceae.
  • the potential plant is a member of the genus Salacia. It will be readily apparent to one skilled in art that other extracts capable of potential positive anti-diabetic properties could be isolated using similar techniques from other known Salacia species and also from a wide range of plants i.e.. potential plants.
  • the potential plants include all species of the family Celastraceae, including terrestrial, aquatic or other plants that can be subjected to standard extraction procedures such as those described herein in order to generate an extract that can be tested for its therapeutic abilities, including but not limited to Salacia oblonga, S. zeylanica, S. chimensis, S. prinoides.
  • the present invention is directed to a herbal medicinal composition comprising the foregoing plant extracts that can be administered to a person suffering from diabetes which results in 5 the lowering of the blood glucose level of the patient.
  • Salacia is a large, straggling, woody shrub with dichotomous branching. It has a smooth bark, which is greenish grey, thin and white inside. The leaves are opposite, elliptic- oblong, base acute, apex abruptly acuminate having toothed margin with minute rounded teeth. It has leathery, hairless, shiny, lateral nerves about seven pairs.
  • extract refers to a concentrated preparation of the essential constituents of the medicinal plant. Typically, an extract is prepared by drying
  • anti-diabetic or hypoglycemic compound or composition generally refers to an agent that lowers blood glucose levels. If blood glucose level is decreased by at least about 100 mg/dl, then the compound is considered to be a hypoglycemic agent.
  • hypoglycemic or anti-diabetic effect can be measured by a variety of methods including, but not limited to, measuring the blood glucose levels, the rate of 5 insulin binding to its receptor, the level of insulin secretion from pancreatic beta cells, and inhibition of glucohydrolase activity.
  • related disorders means disorders related to diabetes mellitus, which include but are not limited to Diabetic Neuropathy, Diabetic Diarrhea, Urinary retention, Gustatory Swelling, Papillary Reflexes, Cardiac Autonomic 0 Disturbances, Collagen Disturbances, thickening of capillary basement membrane, increase in vessel wall matrix and cellular proliferation resulting in vascular complications like lumen narrowing, early atherosclerosis, sclerosis of glomerular capillaries, retinopathy, neuropathy and peripheral vascular insufficiency.
  • potential plants includes plants from which anti-diabetic extracts can be extracted out.
  • the term comprises of plants like Momordica sp., Salacia, Eugenia, Coccimia, Cinammomum sp, Gymnema sp, Ptcrocarpus sp. Azadiricta sp., Trigonella sp. Cymopsis sp.
  • treated extract refers to the dried extract produced after treatment of the concentrated extract with deodourizing/decolorizing agents.
  • herein means an extract containing different compounds from the same plant or from different plants in various combinations.
  • a process for obtaining a plant extract possessing hypoglycemic properties comprising (a) obtaining plant material from one or more plants (b) obtaining an extract from the plant material by contacting the plant material with an aqueous, an ethanolic or an organic solvent, or a combination thereof, thereby providing one or more plant extracts (c) treating the extract with food grade decolorizing agents to obtain an organoleptically improved product (d) analyzing the plant extracts for free radical scavenging potential, Intestinal alpha-glucosidase inhibition potential, insulin mimetic activity and insulin sensitizing activity, in-vitro screening of Salacia root extracts for glucose uptake and the in-vivo efficacy studies.
  • the plant material employed in the extraction process can be the entire potential plant, or it can be one or more distinct tissues from the plant for example, leaves, seeds, roots, stems, flowers, or various combinations thereof but preferably the root of the plant.
  • the plant material may also be treated prior to extraction, for example, by drying, freezing, lyophilizing, or some combination thereof.
  • the plant material can be fragmented and/or homogenized by some means such that a greater surface area is presented to the solvent.
  • the plant material can be crushed or sliced mechanically, using a grinder or other device to fragment the plant parts into small pieces or particles, or the plant material can be frozen liquid nitrogen and then crushed or fragmented into smaller pieces.
  • the solvent used for the extraction process can be aqueous, alcoholic or organic, or a combination thereof.
  • plant material is extracted with an aqueous solvent.
  • suitable solvents include but are not limited to water, buffers, cell media, dilute acids or bases and the like.
  • the plant material is extracted with an alcoholic solvent.
  • suitable alcoholic solvents include, but are not limited to methanol, ethanol, n-propanol, iso-propanol, 2-butanol, ter-butanol, and combinations thereof.
  • the extract is generally produced by contacting the solid plant material with a solvent with adequate mixing and for a period of time sufficient to ensure adequate exposure of the solid plant material to the solvent such that inhibitory activity present in the plant material can be taken up by the solvent.
  • the solvent extraction process may be selected from direct and successive extraction
  • each extraction process typically is conducted over a period of time between about 6 hours to 24 hours at room temperature. Adequate contact of the solvent with the plant material can be encouraged 0 by shaking the suspension.
  • the liquid fraction is then separated from the solid (insoluble) matter resulting in the generation of two fractions: a liquid fraction and a solid fraction, which is the potential extract. Separation of the liquid and solid fractions can be achieved by one or more standard processes known to those skilled in art. 5
  • the potential extracts obtained thereof may be concentrated and solubilised in an appropriate solvent preferably ethyl acetate. Examples of various other organic solvents include but are not limited to, di-ethyl ether, hexane, heptane, dichloromethane, ethyl acetate, butyl alcohol, ether, acetone and the combinations thereof.
  • the puri fied extracts or partially purified extracts are concentrated by solvent removal 0 from the original extract and/or fractionated extract, and/or purified extract.
  • the techniques of solvent removal are known to those skilled in the art and include, but are not limited to rotary evaporation, distillation (normal and reduced pressure), centrifugal vacuum evaporation (speed vac), and lyophilisation.
  • the extract referred to herein can be produced by any of the two procedures stated hcreundcr.
  • the procedures laid down herewith are general procedures alterable with variations known in the art to one skilled in the art. These may not in any way be treated as restrictive .to the instant invention. Accordingly, the product obtained by the process of instant invention has been named as "Minora”.
  • Raw material is cut or pulverized to an approximate 30# size.
  • the pulverized powder is contacted to an aqueous solvent in a ratio ranging from 1 : 5 to 1 :50 (powdcrsolvent).
  • step 3 The mixture prepared in step 2 is stirred continuously for 2- 3 hours at a temperature of 70 0 C - 95°C.
  • Resulting mixture obtained from step 3 is filtered and the filtrate is collected. b). Alternatively, resulting mixture obtained from step 3 is centrifuged (3000 - 4000rpm) and the supernatant is collected.
  • the filtrate / supernatant obtained in step 4 is concentrated, by known procedures such as distillation, or by using roto-evaporator.
  • the concentrated extract so obtained from step 5 is treated with a bleaching agent (ketones) in the ratio ranging from 0.5 : 10 to 10 : 0.5 (extract: bleach ing agent).
  • a bleaching agent ketones
  • the treated extract obtained from step 6 is dried, in particular at a temperature ranging from “55 C to 60 0 C and stored.
  • the treated extract obtained from step 6 may be freeze dried to obtain the final product, which has been named as "Minora”.
  • Example: 2 Procedure B 1 Raw material is cut or pulverized to an approximate 30# size.
  • the pulverized powder is added to alcoholic solvent in a ratio ranging from 1 : 3 to 1 :50 (powde ⁇ solvent).
  • step 3 The mixture prepared in step 2 is stirred continuously for a 2- 3 hours at a temperature of 30 0 C - 45°C. 4. Resulting mixture obtained from step 3 is filtered and the filtrate is collected.
  • resulting mixture obtained from step 3 is centrifuged (3000 - 4000rpm) and the supernatant is collected.
  • the filtrate / supernatant obtained in step 4 or 5 is concentrated, for example by soxhalation, fermentation or rotoevaporator. 7.
  • the concentrated extract so obtained from step 6 is treated with a bleaching agent (ketones) in the ratio ranging from 0.5: 10 to 10 : 0.5. (extract:bleaching agent)
  • the treated extract obtained from step 7 is dried at a temperature ranging from "55 0 C to 60 0 C”.
  • the treated extract obtained from step 7 is freeze dried to obtain the final pi oduct. which has been named as "Minora”.
  • Minora The treated extract is stored in airtight food grade plastic bins and the same is taken through several in-vitro cells free and cell based bioassay to validate the extract efficacy.
  • salacia plant extract can be extracted using varied solvents, solubilizers and concentrantion procedures.
  • Illustrative experiments using a few of the commonly known solvents and solubilizers are stated hereunder. The same are merely illustrative and should not in any way be treated restrictive to the invention.
  • step 2 Approximately l kg of pulverized powder is added to 10 Its of de-ionized water. ( ' I o confirm) 3. The mixture prepared in step 2 is stirred continuously for a 2- 3 hours at a temperature of 80 0 C.
  • the filtrate obtained in step 4 is concentrated, by soxhalation or water based extraction.
  • the treated extract obtained from step 6 is dried, in particular oven dried.
  • step 3 The mixture prepared in step 2 is stirred continuously for a 2- 3 hours at a , temperature of 40 0 C. v
  • step 5 The filtrate obtained in step 4 is concentrated, by soxhalation or water based extraction. 6.
  • the concentrated extract so obtained from step 5 is treated with H 2 O 2 in the ratio of 1 : 0.25.
  • the treated extract obtained from step 6 is dried, in particular oven dried.
  • a 15-member panel of judges for comparing the organoleptic properties of the extracts so produced by making use of the invention was constituted. Properties like, taste, flavor, color and overall acceptability were characterized. A grading system from 1 - 5 was generated wherein 1 meant poor and 5 meant excellent. A mean of readings generated by the judges was taken. Results obtained for two of the batches are laid down hereunder as table 1.
  • Insulin-stimulated glucose uptake in adipose tissue and striated muscle is critical for reducing postprandial blood glucose concentration and the dysregulation of this process is one of the hallmarks of Type -II Diabetes mellitus (Non Insulin dependent). Oral therapies for Diabetes mellitus have emerged out of this interest and are widely used still today. But rather than acting by mimicking insulin, these drugs acts either by stimulating insulin release [Sulphonylurcase], potentiating insulin action (thiazolidinedione) or lowering hepatic glucose production (biguanides).
  • Various amounts of Salacia aqueous and alcoholic extracts (0.034 ⁇ g to 33.4 ⁇ g) are tested for insulin mimetic and sensitization effects with / without insulin. Insulin mimetic activity shown by salacia extracts
  • Radio labeled glucose is used to measure the changes in the level of glucose uptake activity of the adipocyte cells in response to treatment with samples in the presence or absence of insulin.
  • the assay is performed in a 96-well microtiter plate format and the counts per minute are measured using a radioactive counter. The count per minute can be measured on a microtiter plate by radioactive counter.
  • Insulin mimetic activity was tested in both 3T3-1 adipocyte cells and C2C12 myocyte cells. Three different concentrations of salacia extract were used. Both aqueous extracts and alcoholic extracts were tested. Both extracts showed insulin mimetic activity in
  • Insulin sensitization activity was tested in both 3T3-1 adipocyte cells and C2C 12 myoblast cells. Three different concentrations of salacia extract were used. Both aqueous extracts and alcoholic extracts were tested. Both extracts showed insulin- sensitizing activity in all concentrations. The results obtained arc stated in table and shown in figures 4, 5.
  • Table 6 Glucose Uptake studies using 3T3L-1 adipocyte cells for salacia aqueous extract showing insulin sensitization activity
  • Table 8 Glucose Uptake studies using C2C12 cells for salacia aqueous extract showing insulin sensitization activity
  • Prcadipocytcs (3 1 ' 3L-I ) and premyocytes (C2C I 2) are cultured in DMEM containing 10%FCS, 4mM Glutamine, 2% NaHCO3 and antimycotic, in an atmosphere of 5% CO2 at 37 0 C, separately.
  • Myoblasts are cultured up to 80% confluency and the cells are sub-cultured at three-day intervals.
  • 20,000 of preadipocytes and myocytes are seeded separately in each well of a 96 well plate and differentiated for 48 hours in DMEM:F 12(1 : 1 ), 0.5mMIBMX, 0.25mM Dexmethasone and l ug Insulin for 48hrs followed by incubation with l ug of Insulin for 8hours.
  • the ability of the plant extract to induce glucose uptake is tested in two different ways 1 ) glucose uptake in presence of insulin (extract + insulin) and 2) glucose uptake in absence of insulin (extract alone). Therefore incubate in duplicate (one set to evaluate glucose uptake in presence of insulin i.e. extract + insulin and other set without insulin i.e.
  • oligosacharrides (carbohydrates having 2 to 10 glucose residues connected by 1 -4 or 1 -6 ⁇ -D-glycosidic linkage) into monosaccharides by alpha-gliicohydrolasc-catalyzcd enzymatic reactions was tested for Salacia water root extract using Calorimetric - para-nitro-phenyl (pNP) release method using pNP-a-D- glucoside.
  • the Salacia water extract showed greater ⁇ -glucosidase inhibition potential (IC50 value of 51.45 ⁇ g/ml) relative to the commercially available ⁇ - glucosidase inhibitor, acarbose (IC50 value of 146.55 ⁇ g/ml) for 0.2 ⁇ -glucosidase enzyme units at standard enzymatic reaction conditions. The same has been depicted in figure 7 .
  • the isolated extracts were used to estimate its free radical scavenging potency relative to ascorbic acid by using Calorimetric-DPPH method (Polterait O. (1997) Anti Oxidants and free-radical Scavengers of Natural origin
  • the total polyphenol content of the Salacia water extract was estimated relative to gallic acid using Calorimetric - Singleton method (Singleton, V. L. and Ropssi, J. A. Jr ( 1965).
  • the Salacia water extract showed 21 ⁇ 2.25 % total phenol content equivalent to gallic acid clearly indicative of the potential beneficial effects the extracts possess with respect to the management of diabetes and its medicative properties.
  • the results are represented in the form of bar graph in figure 9.
  • the present invention envisages the method of treating diabetes and other related diseases thereof by administering an effective amount of the therapeutic composition comprising the single plant extract or the screened plant extracts purified there from in combination.
  • the therapeutic compositions of the invention can be administered alone or in combination with one or more standard anti-diabetic therapeutics.
  • the present invention also contemplates the administration of sub-optimal doses of the therapeutic composition, for example, chemotherapcutic drug(s), in combination with the therapeutic composition.
  • one or more plant extracts in order to prepare a therapeutic combination, one or more plant extracts is first selected and then the efficacy of the extract(s) in controlling diabetes and maintaining glucose homeostasis is determined using standard techniques as one of those outlined above.
  • the efficacy of the one or more plant extract alone is then compared to the efficacy of the one or more plant extract in combination with varying amounts of another component i.e., another plant extract.
  • the invention also contemplates the combination the plant extract with another synthetic inhibitor.
  • a combination that demonstrates therapeutic index in comparison to the individual properties is considered to be an effective combination.
  • compositions comprising two or more plant extracts various ratios of the constituent plant extracts are contemplated.
  • the ratio of extract A to extract B can vary anywhere between 1 :99 and 99: 1.
  • anywhere between 99: 1 and 1 :99 it is meant that the ratio of the two extracts can be defined by any ratio within this ratio can be between 98:2 and about 1 :99 between about 98:2 and 2:98, between 97:3 and 1 :99, between 97:3 and 2:98, between 97:3 and 3:97, etc.
  • the present invention contemplates the ratio of the two extracts is between about 90: 10 and 10:90, 80:20 and 20:80. 70:30 and 30:70, 60:40 and 40:60 or 50: 50.Analogous ratios are contemplated for compositions comprising more than two or more plant extracts.
  • the formulations of the present invention contain at least an effective amount of the therapeutic composition.
  • the effective amount is considered to be that amount of the composition, in weight percent of the overall formulation, which must be present in oidcr to produce the desired therapeutic effect.
  • the effective amount may vary, depending upon, for example the disease to be treated and the form of administration.
  • the therapeutic composition will be present in an amount ranging from about 1% to 100% by weight of the formulation, 10% to about 90% by weight of the formulation, 20% to about 80% by weight of the formulation, 30% to 70% by weight of the formulation, from about 40% ' to 60% by weight of the formulation and about 50% by weight of the formulation.
  • the present invention contemplates the use of the therapeutic compositions at various stages in the disease development and progression, including in the treatment of early stage, or advanced and/or aggressive stage of hyperglycemia, diabetes or related disorders.
  • the administration of the therapeutic composition comprising the isolated and screened extracts to mammal having an early stage of the disorder can help to attenuate the progression of the disease.
  • I he dosage of the therapeutic composition to be administered is not subject to defined limits, but will usually be an effective amount. However it will be understood that the actual amount of the composition to be administered will be determined by a physician, in the light of the relevant circumstances, including the exact condition to be treated, the chosen route of administration, the actual composition administered, the age, the weight, and the response of the individual patient and the severity of the patient's symptoms. ' I he dosage ranges are not intended to limit the scope of the invention in any way.
  • the therapeutic compositions comprising the plant extract are not limited to only those for humans but also include those for various animals, in particular, other mammals. Therefore, the food compositions include foods for animals such as cats, dogs, and the like pets, and the medical compositions include those for animals other than humans.
  • the therapeutic composition can be formulated as a pharmaceutical or naturopathic formulation such as phytoceuticals or nutraceuticals, for oral, topical, rectal or parenteral administration or for administration by inhalation or spray.
  • the phytoceutical or naturopathic formulation may comprise the one or more plant extracts in dosage unit formulations containing the conventional non-toxic physiologically acceptable carriers, adjuvants and vehicles.
  • the pharmaceutical or naturopathic formulations may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion hard or soft capsules, or syrups or elixirs.
  • the therapeutic compositions of the invention may be formulated as phytoceuticals, or nutraceuticals.
  • Phytoceuticals may optionally comprise other plant-derived components and can therefore be delivered by such non-limiting vehicles as teas, tonics, juices or syrups.
  • Nutraceuticals contemplated by the present invention may provide nutritional and/or supplemental benefits and therefore be delivered, for example as foods, dietary supplements, extracts, beverages or the like.
  • Phytoceutical and nutraceuticals can be administered in accordance with conventional treatment programs and/or may be a part of the dietary or supplemental program.
  • Formulations intended for oral use may be prepared according to methods known in art for the manufacture of pharmaceutical compositions and may contain one or more agents selected from the group of flavoring agents, coloring agents and preserving agents in order to provide palatable preparations.
  • Tablets contain the active ingredient in admixture with suitable non-toxic physiologically acceptable excipients including, for example, inert diluents, such as calcium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, such as com starch, or alginic acid, binding agents, such as starch, gelatine or acacia, and lubricating agents, such as magnesium stearate, stearic acid or talc.
  • suitable non-toxic physiologically acceptable excipients including, for example, inert diluents, such as calcium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, such as com starch, or alginic acid, binding agents, such as starch, gelatine or acacia, and lubricating agents, such as magnesium stearate, stearic acid or talc.
  • the tablets can be uncoated, or they may be coated by
  • additives or carriers can be incorporated into the orally delivered pharmaceutical naturopathic formulations or the invention.
  • Optional additives of the present composition include, without limitation, phospholipids, such as phosphatidyl glycerol, phosphotidyl inositol, phosphotidyl serine, phosphotidyl choline, phosphotidyl ethanolamine as well as phosphatidic acids, ceramide, cerebrosides, sphingomyelins and cardiolipins.
  • compositions for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil based medium such as peanut oil, liquid paraffin or olive oil.
  • an inert diluent for example, calcium carbonate, calcium phosphate or kaolin
  • soft gelatin capsules wherein the active ingredient is mixed with water or an oil based medium such as peanut oil, liquid paraffin or olive oil.
  • Oily suspensions may be formulated by suspending the plant extract(s) in a vegetable oil, for example, arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin.
  • the oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol.
  • Flavoring agents may be added to provide palatable oral preparations. These formulations can be preserved by the addition of an anti-oxidant such as ascorbic acid.
  • Dispersible powders and granules suitable for preparation suitable for an aqueous suspension by the addition of water provide the active ingredient in admixture with dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents, sweetening, flavoring and coloring agents may also be present.
  • the extract produced by the invention can be used in combination with other known extracts from different plant sources.
  • the instant invention can be prepared and used in combination with other therapeutic agents such as well known drugs selected from the groups consisting of sulfonylurea, a biguanide, a thiazolidinedione, a P3-adrenergic receptor agonist, an alpha.-glycosidase inhibitor, insulin and mixtures thereof.
  • the common yet delimiting examples of such drugs are biguanide such as metformin or buformin; a sulfonylurea such as acetohexamide, chlorpropamide, tolazamide, tolbutamide, glyburide, glypizide or glyclazide; a thiazolidinedione such as troglitazone; an a-glycosidase inhibitor such as acarbose or migiatol, or a P3-ad ⁇ energic receptor agonist such as CL-3 16, 243, etc; or mixtures thereof.
  • biguanide such as metformin or buformin
  • a sulfonylurea such as acetohexamide, chlorpropamide, tolazamide, tolbutamide, glyburide, glypizide or glyclazide
  • a thiazolidinedione such as troglitazone
  • a comestible that is to say, a foodstuff comprising at least an extract of the invention, typically in dried form, such as in a lyophilized form.
  • comestibles may contain more than one extract of the invention and may be used.
  • Such foodstuffs may be used in a prophylactic manner and may contain further extracts having a similar function to the first added extract or further added extracts may be added that have a di lTcienl prophylactic function.
  • a foodstuff could either comprise extracts that provide for a comestible having a single functional aspect, or a comestible may have a multi-functional prophylactic effect against two or more disease types.
  • I he type of foodstuff or comestible to which at least an extract of the invention may be added includes any processed food such as confectionaries, baked products including breads such as loafs, and flat breads such as pitta bread, naan bread and the like, cakes, snack foods such as museli bars, compressed dried fruit bars, biscuits, dairy products such as yoghurts, milk and milk-based products such as custards, cream, cheese, butter and crmc fraichc.
  • simulated dairy food product such as Elmlea products, fruits and vegetable juices, aerated drinks, such as carbonated soft drinks and non-aerated drinks such as squashes, soya milk, rice milk and coconut milk and the like, pastas, noodles, vegetables, seed and nut oils, fruited oils such as sunflower oil, rapeseed oil, olive oil, walnut, hazelnut, and sesame seed oil and the like, and frozen confectionaries such as ice cream, iced yoghurts and the like.
  • flic present water and cthanol based plant extracts can also be used for the management of diabetic related disorders, which are general, or local diseases directly or indirectly caused by diabetes.
  • diabetic acidosis diabetic xanthoma, diabetic myatrophy, diabetic ketosis, diabetic coma, diabetic stomach disorders, diabetic gangrene, diabetic ulcer, diabetic diarrhea, diabetic microangiopathy, diabetic uterosclerosis, diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, diabetic blister, diabetic cataract, diabetic dermatitis, diabetic scleredema, diabetic retinopathy, diabetic necrobiosis lipoidica, diabetic blood flow obstructions, etc
  • the present invention relates to mixtures, which can be isolated from Salacia bark (Celastraccae family) for the management of an important clinical problem like diabetes.
  • the following examples set forth and present the effects of Salacia species on both pre-existing diabetes conditions, as well as the preventative effects of Salacia species against the onset of or contracting diabetes. These examples are not intended to be limiting in any way, but are merely illustrative of the beneficial, advantageous, and remedial effects of Salacia species on diabetes.
  • Sprague dawley rats weighing ⁇ 250g with a variation of + 20% of the mean weight are selected for In-vivo efficacy screening of Salacia root water extract.
  • the identification is undertaken by the cage tag arid the. corresponding picric acid color body markings.
  • the number of animals selected in a group is five and kept in an experimental room after veterinary examination.
  • the route of administration is oral gavage.
  • the rats are fed with 5 % glucose water for two days before STZ injection to avoid death due to hypoglycemic shock. Rats are fasted for 12 hours and injected intraperitoneally with 45mg/kg-body weight of streptozotocin. Blood collection is undertaken with CO2 anesthesia and FBG analysis before STZ injection is performed which serves as the normal baseline (60-120mg/dI) for the animals.
  • Citrate buffer (Ph of 4.5) is used as the vehicle STZ is a photo, temperature and Ph sensitive chemical; hence the animals are injected with in 45 minutes of the dose formulation.
  • the dosing formulations are prepared freshly each day 0.5% CMC was used as the vehicle.
  • the test article Salacia root water extract, is administered by oral gavage to each rat daily, for 35 consecutive days.
  • the animals were dosed at approximately the same time each day where possible using a stainless steel intubation needle fitted onto a suitably graduated glass syringe.
  • the dosage volume administered to individual rat was adjusted according to its most recently recorded body weights. Treatment in this manner continued once a day, seven days a week, for a total period of 35 days.
  • Vehicle control group animals are treated with the vehicle only at the same dosage volume i.e. 10 ml/kg body weight.
  • the Groups include: G l -Vehicle control, G2-Diabetic control, G-3 Diabetic animals treated with Pioglitazone (Standard anti-diabetic drug) 20mg/kg-body weight.
  • G-4 Salacia water root extract 50 mg/kg-body weight
  • G-5 Salacia water root extract 125 mg/kg-body weight
  • G-6 Salacia water root extract 200 mg/kg-body weight.
  • the fasting blood glucose lowering potential of Salacia water root extract at different concentrations are illustrated in figure 10.
  • the diabetic control rat group showed 240% increase in their fasting blood glucose levels compared to the baseline values of the same group at the start of the study. While the groups treated with pioglitazone, Salacia water root extract at 50, 125 and 200mpk (milligram per kg body weight) did not show any significant percent change from their baseline values. The results have been represented in Table No. 10 Table 10: Fasting Blood Glucose
  • the postprandial blood glucose lowering potential of Salacia root water extracts at different concentrations are illustrated in figure 11.
  • the diabetic control rat group showed over 240% increase in their postprandial blood glucose levels compared to the baseline values of the same group at the start of the study. While the groups treated with pioglitazo ⁇ c, Salacia root water extract at 50, 125 and 200mpk (milligram per kg body weight) did not show any significant percent change from their baseline values. The results have been represented in Table No. 1 1
  • Acute oral toxicity study of Ant diabetic Extract - AGT028Ro08(00) in Sprague Dawley rats was performed in compliance with the OECD Guidelines for Testing of Chemicals, Section 4, No. 423 - Acute Oral Toxicity - Acute Toxic Class Method, adopted 17 December, 2001.
  • the method uses pre-defined doses and the results allow a substance to be ranked and classified according to the Globally Harmonised System (Gl IS) lor classification of chemicals which cause acute toxicity.
  • Gl IS Globally Harmonised System
  • CMC Cerecranial Sprague Dawley rats
  • Antidiabetic Extract - AGT028Ro08(00) did not cause death of any of the treated females. Also, no abnormal clinical signs were observed in the six female rats.
  • Antidiabetic Extract - AGT028Ro08(00) was further tested at the dose of 5000 mg/kg, on three female rats in stepwise manner.
  • the test article did not cause death of any of the female rats treated at 5000 mg/kg after dosing and also did not induce any signs of evident toxicity.
  • Antidiabetic Extract - AGT028Ro08(00) at the dose levels of 2000 mg/kg and 5000 mg/kg body weight, did not adversely affect body weight gain by treated rats during the 14 day observation period, post-treatment.
  • the test article did not induce any gross pathological alterations in the tissues / organs of the treated rats as was evident during the terminal necropsy.
  • GHS Globally Harmonised System
  • Antidiabetic Extract - AGT028Ro08(00) has to be classified as GHS Category 5 or Unclassified for the obligatory labeling requirement for oral toxicity.
  • This category indicates that following acute oral exposure to Antidiabetic Extract - AGT028Ro08(00) in female rats, the LD50 value is expected to exceed 5000 mg/kg.
  • This category indicates that following acute oral exposure to Antidiabetic Extract - AG I 028Ro08 (00) in female rats, the LD50 value is expected to exceed 5000 mg/kg.
  • the rats were examined daily for signs of toxicity and mortality, and were subjected to detailed clinical examination before initiation of the experiment and weekly thereafter during the exposure period and reversal period. In the fourth week of exposure they were additionally examined for assessment of sensory reactivity, assessment of grip strength and motor activity. Body weight and food consumption were recorded weekly.
  • Antidiabetic Extract - AGT028Ro08(00) was evaluated in the Ames / Salmonella Plate Incorporation Assay to determine its ability to induce reverse mutation at selected histidinc loci in five tester strains of Salmonella typhimurium viz.
  • Dimethyl sulphoxidc was used as a vehicle.
  • the exposed bacteria were plated onto minimal glucose agar medium supplemented with L-histidine.
  • the plates were incubated at 370 C for 48 hours after which the histidine revertant colonies were counted and their frequency was compared with that in the vehicle control group.
  • Results of this test indicated that the frequencies of histidine revertant colonies at all concentrations of Antidiabetic Extract - ⁇ GT028Ro08(00) in strains TA 1535, TA 97a, TA 98, TA 100 and TA 102, with and without the presence of a metabolic activation system, were comparable to those observed in the vehicle control groups, and this observation was confirmed by repetition of the experiments.
  • Antidiabetic Extract - AGT028Ro08(00) by Salmonella typhin ⁇ inum Reverse Mutation Assay was carried out following the OECD Guidelines for Testing of Chemicals (No. 471 , Section 4 : Health Effects) on conduct of "Bacterial Reverse Mutation Test", adopted 21 July 1997. It is concluded that, under the conditions of this study, Antidiabetic Extract -
  • AGT028Ro08(00) is non-mutagenic in Salmonella typhimurium strains TA 1535, TA 97a, TA 98, TA 100 and TA 102.

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Abstract

L'invention porte sur une méthode améliorant les propriétés organoleptiques et anti-diabétiques d'un extrait de Salacia, et sur l'extrait amélioré ainsi produit présentant une efficacité renforcée pour le traitement du diabète et des troubles associés.
PCT/IN2007/000263 2007-05-07 2007-06-29 Extrait organoleptiquement amélioré de salacia et méthode associée (minora) WO2008136013A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015075549A1 (fr) * 2013-11-19 2015-05-28 OmniActive Health Technologies (Canada) Limited Compositions à base de salacia, méthodes de traitement impliquant leur administration et leurs procédés de préparation
US9999643B2 (en) 2016-10-19 2018-06-19 Sultan Qaboos Univeristy Therapeutic composition for treating gangrene

Citations (2)

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Publication number Priority date Publication date Assignee Title
US5691386A (en) * 1996-04-16 1997-11-25 Shaman Pharmaceuticals, Inc. Triterpenoid compound for the treatment of diabetes
US20020041904A1 (en) * 2000-02-01 2002-04-11 Takama Systems, Ltd. Compound with alpha-glucosidase inhibiting action and method for producing the same

Patent Citations (2)

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Publication number Priority date Publication date Assignee Title
US5691386A (en) * 1996-04-16 1997-11-25 Shaman Pharmaceuticals, Inc. Triterpenoid compound for the treatment of diabetes
US20020041904A1 (en) * 2000-02-01 2002-04-11 Takama Systems, Ltd. Compound with alpha-glucosidase inhibiting action and method for producing the same

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Title
HEACOCK P.M. ET AL.: "Effects of a medical food containing an herbal alpha-glucoside inhibitor on postprandial glycemia and insulinemia in healthy adults", J. AMER. DIET ASSOC., vol. 105, 2005, pages 65 - 71 *
LI Y. ET AL.: "Salacia oblonga improves cardiac fibrosis and inhibits postprandial hyperglycemia in obese zucker rats", LIFE SCIENCE, vol. 75, 2004, pages 1735 - 1746 *
SERASINGHE S. ET AL.: "Oral hypoglycaemic effect of Salacia reticulata in the streptozotocin induced diabetic rat", PHYTOTHERAPY. RESEARCH, vol. 4, no. 5, 1990, pages 205 - 206 *
VENKATESWARLU V. ET AL.: "Antidiabetic activity of roots of Salacia macrosperma", PLANTA MEDICA, vol. 59, 1993, pages 391 - 393 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015075549A1 (fr) * 2013-11-19 2015-05-28 OmniActive Health Technologies (Canada) Limited Compositions à base de salacia, méthodes de traitement impliquant leur administration et leurs procédés de préparation
US9849151B2 (en) 2013-11-19 2017-12-26 OmniActive Health Technologies (Canada) Limited Salacia compositions, methods of treatment by their administration, and methods of their preparation
US9999643B2 (en) 2016-10-19 2018-06-19 Sultan Qaboos Univeristy Therapeutic composition for treating gangrene

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