EP2010197A2 - Pharmazeutische zusammensetzung als immunomodulierendes mittel und verfahren zu ihrer herstellung - Google Patents

Pharmazeutische zusammensetzung als immunomodulierendes mittel und verfahren zu ihrer herstellung

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Publication number
EP2010197A2
EP2010197A2 EP07734177A EP07734177A EP2010197A2 EP 2010197 A2 EP2010197 A2 EP 2010197A2 EP 07734177 A EP07734177 A EP 07734177A EP 07734177 A EP07734177 A EP 07734177A EP 2010197 A2 EP2010197 A2 EP 2010197A2
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EP
European Patent Office
Prior art keywords
chlorophytum
polysaccharides
water
polysaccharide
plant
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP07734177A
Other languages
English (en)
French (fr)
Inventor
Rajender Singh Sangwan
Narayan Das Chaurasiya
Laxmi Narain Misra
Payare Lal
Girish Chandra Uniyal
Neelam Singh Sangwan
Avdhesh Kumar Srivastava
Krishan Avtar Suri
Ghulam Nabi Qazi
Rakesh Tuli
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Council of Scientific and Industrial Research CSIR
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Council of Scientific and Industrial Research CSIR
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Publication date
Application filed by Council of Scientific and Industrial Research CSIR filed Critical Council of Scientific and Industrial Research CSIR
Publication of EP2010197A2 publication Critical patent/EP2010197A2/de
Withdrawn legal-status Critical Current

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Classifications

    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators

Definitions

  • the present invention relates to a pharmaceutical composition useful as an immunomodulating agent and a process for the preparation thereof. In general it is directed toward use and applications of Chlorophytum (Safed Musli) as potential immunomodulatory, health promoting, nutraceutical herb.
  • the invention particularly relates to a process for isolating immunomodulatory carbohydrate/polysaccharide including but not limited to Chlorophytum Musli Glucomannan (MGM).
  • MGM Chlorophytum Musli Glucomannan
  • the present invention further relates to purified compositions of the plant aqueous extracts.
  • the current invention is directed toward a botanical substance from Safed Musli for immune-response enhancement and curing diseases and ailments related to immunity by prevention of suppression of immunity for any purpose or in any way through the use of the plant in any physical or chemical form.
  • the plant genus Chlorophytum belongs to the family Liliaceae.
  • the genus Chlorophytum is represented by about 175 valid taxa of rhizomatous herbs distributed predominantly in the tropical and parts of the world and some of them cultivated for ornamental flowers. Its probable centres of origin and diversification lie in tropical and subtropical Africa and Asia where where 85% of the species are found [PC Bordia, A. Joshi and M.M. Simlot 1995 Safed Musli In Advances in Horticulture volume 11 (Medicinal and Aromatic Plants) Editors: K.L. Chadha and Rajendra Gupta, pp.430- 450, Malhotra Publishing House, New Delhi, India].
  • Genus-specific features of Chlorophytum are fleshy roots/root tubers (fasciculated roots) and attractive green leaves. Leaves are radical, spirally imbricate at the base with acute apex spreading horizontally. The flowers are usually white with ornamental attraction. The plants are monoecious or dioecious herbs, bushes or trees with varied growth habits exhibiting stalks or branches differentiated into two to three different types [PC Bordia, A. Joshi and M.M. Simlot 1995 Safed Musli In Advances in Horticulture volume 11 (Medicinal and Aromatic Plants) Editors: K.L. Chadha and Rajendra Gupta, pp.430-450, Malhotra Publishing House, New Delhi, India].
  • Typical phytochemical representatives of Chlorophutum species believed to be active ingredients so far are the low molecular weight terpenoidal phytochemicals like glycosides/saponins of putatively steroidal/spirostanol skeletal molecules like hecogenin [PC Bordia, A. Joshi and M.M. Simlot 1995 Safed Musli In Advances in Horticulture volume 11 (Medicinal and Aromatic Plants) Editors: K.L. Chadha and Rajendra Gupta, pp.430-450, Malhotra Publishing House, New Delhi, India; S.Mimaki, T. Kanmoto, Y. Sashida, A. Nishino, Y. Satomi and H.
  • Sapogenins like stigmasterol, sarsasapogenin, togogenin, neogitogenin and tokorogenin have been shown to be minor constituents (0.0012%, 0.0003%, 0.0003%, 0.0003%, 0.0005%, respectively on dry weight basis have been isolated from Chlorophytum arundinaceum ( M. Tandon and Y.N. Shukla, Sapogenins from Asparagus adscendens and Chlorophytum arundinaceum J. Indian Chemical
  • KGM is beneficial to the health of human beings and its ability to cure some diseases is well documented (W. Fang and P. Wu Variation of Konjac glucomannan, KGM from Amorphophallus konjac and its refined powder in China, Food Hydrocolloids 18: 167-170, 2004).
  • Polysaccharides are unique in plant specific manner as well as monomeric composition in proportion and sequence are important with respect to biological properties as well as other physical properties (like gelation, colloids) that comprehensively ascribe them wide and specific utilities as materials useful in food, pharmaceutical, cosmetic and related biomedical industries.
  • the invention relates to the use of Chlorophytum (Safed Musli) or its one or more polyglyco-component(s) or substances or mixtures of substances obtained therefrom for the prevention or treatment of immunity related problems, risks, disorders, ailments and diseases and secondary consequences thereof.
  • the main object of the present invention is thus to provide a process for the isolation of bioactive polysaccharides from Chlorophytum sp (Safed musli).
  • Another object of the present invention is to provide a pharmaceutical composition useful as an immunomodulating agent comprising of isolated polysaccharide fractions from the tubers/ fingers (fasciculated roots) of the plant Chlorophytum borivillianum.
  • Still another object of the present invention is to provide Chlorophytum sp. (Safed musli) as an immunomodulating agent comprising upto 45% (w/w) isolated polysaccharides, 7 to 10 % (w/w) proteins and 40 to 50% (w/w) of other constituents such as fiber, cellulose, pectin, hemicellulose and free sugars.
  • Yet another object of the present invention is to provide a pharmaceutical composition having humorral immunomodulatory activity greater than levamisole, a positive control employed in the test systems for immunomodulatory activity.
  • a further object of the present invention is to provide a herbal non-toxic pharmaceutical composition useful as an immunomodulator.
  • Yet another object of the present invention is to provide a simple and easy method for the extraction of water soluble and hydro-suspension polysaccharides from safed musli.
  • the invention relates to the use of Chlorophytum or its aqueous component(s) ['water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' glucomannan polysaccharides' etc.], or substances or mixtures of substances obtained therefrom for the health benefits with respect to immune- enhancement and immunomodulatory properties associated with the polysaccharides/MGM amassed in the herb.
  • the immune enhancing ability of the Chlorophytum or its extracts to 'water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' glucomannan MGM polysaccharides' as embodied in the claims or its polymeric carbohydrates including but not limited to 'water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' MGM extract is preferably determined by performing in vivo assays.
  • the invention relates to the use of Chlorophytum or its aqueous 5 components or substances or mixture of substances obtained therefrom for the production of nutraceutical, dietary supplement, edible additives, pharmaceutical composition for the health benefits like immune strength, antiglycaemic etc. drawn from its novel polysaccharides ['water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' glucomannan
  • the invention relates to the use of Chlorophytum or its aqueous components or substances or mixtures of substances obtained therefrom for making the immune system potentiating and in the preparation of anti-glycaemic formulations,
  • nutraceuticals 15 nutraceuticals, foods, functional foods, dietary supplements and food processing ingredients.
  • the present invention provides a process for the isolation of bioactive polysaccharides from Chlorophytum sp (Safed musli) comprising the steps of :
  • step [b] adding 4 volumes of ethanol to the supernatant of step [a] to precipitate the polysaccharides;
  • step [c] dissolving the precipitated polysaccharide obtained from step [b] in water under stirring followed by filtration to obtain a filterate and a residue;
  • the invention further provides a pharmaceutical composition useful as an immunomodulating agent comprising isolated polysaccharide fractions from the plant Chlorophytum borivillianum consisting of water extractable easily water soluble polysaccharides and water extractable hydro-suspension polysaccharides either alone or in combination optionally along with pharmaceutically acceptable excipients.
  • Chlorophytum sp.(Safed musli) as an immunomodulating agent comprising upto 45% (w/w) isolated polysaccharides, 7 to 10 % (w/w) proteins and 40 to 50% (w/w) of other constituents such as fiber, cellulose, pectin, hemicellulose and free sugars.
  • the extraction may be carried out at any temperature upto boiling point of the extraction medium.
  • the ethanol precipitated carbohydrates may be redissolved in normal or alkaline water and deproteinized.
  • deproteinization may be carried out by precipitation with TCA, sodium acetate or by other routine way of selective precipitation of proteins
  • the deproteinized supernatant may be subjected directly to ethanol precipitation for sedimenting carbohydrate or after its desalting by dialysis or otherwise.
  • the deproteinized polysaccharide preparation may be partially or completely purified through ion-exchange chromatography and/or size exclusion chromatography.
  • the yield of bioactive polysaccharide fractions is 8% w/w for 'water extractable easily water soluble polysaccharides' (Bio-RSID) and 15% w/w.for 'water extractable hydro-suspension polysaccharides' (Bio-RSIF).
  • the fraction is isolated from Chlorophytum borivillianum.
  • the plant tissue/biomass is preferably aerial or tubers/ fingers (fasciculated roots) or mixtures thereof.
  • the plant tissue/biomass is extracted or used fresh or dry and may be native or peeled or in any other physical form.
  • the dose of the composition is 50 to 100mg/Kg body weight administered orally for a period of l-28days.
  • the amount of RBCs used to induce the humorral immunity was 0.2 ml of 1 x 10 8 red blood cells.
  • the composition is non toxic in rodents as experimentally studied upto a dose of 2000mg/Kg body weight in single oral dose.
  • the humorral immunomodulatory activity of the composition is greater than levamisole, a positive control employed in the test systems for immunomodulatory activity.
  • the cell mediated immunomodulatory activity of the composition is greater than normal and cyclophosphamide treated animals, a control employed in the test systems for delayed type hypersensitivity reaction to measure the cell mediated immunomodulatory activity.
  • the extraction process of the present invention is desirably carried out using an aqueous solvent, inclusion of other salts or solvents is acceptable so far as it does not jeopardize the extraction of polymeric carbohydrates including but not limited to 'water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' heteroglycans like MGM.
  • the invention further relates to methods for the prevention or treatment of diseases or health risks wherein one or more CMorophytum or its aqueous components or substances ['water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' glucomannan polysaccharides' etc.] or mixtures of substances obtained therefrom are administered to the mammal.
  • one or more CMorophytum or its aqueous components or substances ['water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' glucomannan polysaccharides' etc.] or mixtures of substances obtained therefrom are administered to the mammal.
  • the aqueous extract or components of the herb are selected from a group of polymeric carbohydrates, particularly ['water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' CMorophytum /Musli glucomannan polysaccharides (MGM)' etc.
  • CMorophytum parts comprise all botanical parts of the herb.
  • aqueous extract includes extraction made in water in presence or absence of other solutes or diluents at any temperature to yield the mixture of glycans.
  • extraction implies to solubilize substances or 5 mixtures of substances in order to recover them in their preferred solvation method from the tissue matrix based on their cellular localization and physico-chemical properties including requirement of additives in the water to aid extraction.
  • alcohols and/or a mixture thereof can be used for the extraction, purification or precipitation of the substance or the mixture of
  • polymeric/oligomeric carbohydrate compounds are like but not limited to 'water extractable easily water soluble polysaccharides', 'water extractable hydro-suspension polysaccharides' MGM demonstrated to exist in the plant may be isolated and purified by persons of ordinary skill in the art employing methods given herein as embodiments
  • the immunomodulatory activity may be obtained by column chromatography (ion-exchange, size exclusion), selective precipitation, deproteinization, freeze-thawing, dialysis etc. to obtain partially or completely pure compounds from the plant.
  • the immunomodulatory activity may be obtained by column chromatography (ion-exchange, size exclusion), selective precipitation, deproteinization, freeze-thawing, dialysis etc. to obtain partially or completely pure compounds from the plant.
  • the immunomodulatory activity may
  • the immunomodulatory benefits concern both cellular and humoral.
  • the immunomodulatory benefits concern both cellular and humoral.
  • 25 include primary, secondary, direct or indirect.
  • the health promotion potential of the herb or its pure or impure polysaccharide substances extends to those implied in the property of the substances referred herein. It has been observed that aqueous extract of Chlorophytum possess immune response
  • aqueous extracts may be used to have immunological health gain for normal and suffering person from the plant or its part or its extract or aqueously extracted substance from them.
  • these aqueous extracts are nutraceuticals that may be safely consumed for preventive, curative or supportive or strengthening for immune system and response.
  • the aqueous extracts of the present invention are preferably isolated from a plant that has a history of safe consumption for long. 5
  • aqueous extracts are isolated from Chlorophytum species.
  • the applications include an oral or topical or other means in practice in food, health, biomedical and cosmetic.
  • Plant Material Plants of Chlorophytum borivillianiim were raised at the experimental farm of Central Institute of Medicinal and Aromatic Plants, Lucknow (India) following standard agronomic practices, At the crop maturity, the tubers (fasiculated roots) were harvested by digging out and were surface-peeled off and were shade dried to complete 15. dryness and stored in a cool dry place until used.
  • Bio-RSID water extractable easily water solubilizable polysaccharide
  • Characterization of the Polysaccharide The water soluble polysaccharide fraction (Bio- RS-ID) was subjected to molecular sieve exclusion chromatography through Sephacryl HR-200 column. For this, an aliquot (0.5 ml) of the polysaccharide was loaded on to a molecular weight calibrated column (38.5X 1.4 cm) of Sephacryl HR-200 (void volume 17.5 ml) and the column was eluted with distilled water and fractions (2.0 ml) collected.
  • the polysaccharides identity was discerned through its compositional analysis in terms of the nature of the constituent repeating unit of monosaccharide(s).
  • the polysaccharide was subjected to hydrolysis with TFA (tri-fluoro acetic acid) and thin layer chromatography (TLC) of the hydrolyzed as well as unhydrolyzed poilysaccharide.
  • TFA tri-fluoro acetic acid
  • TLC thin layer chromatography
  • the solution of the polysaccharide was subjected to hydrolysis with 2M TFA in a boiling water bath for 5 hours in a sealed glass tube. After hydrolysis . the mixture was neutralized by the addition of sodium bicarbonate till effervescence stopped.
  • the plate was heated at 110 0 C for 10 minutes and spots of authentic standards and sample hydrolysate were visualized and compared.
  • the comparative analysis of migration of the hydrolyzed products from the polysaccharide and the standard monosaccharides revealed that the hydrolyzed products were glucose and mannose, thus, discerning that the polysaccharide is glucomannan.
  • the Safed Musli glucomannan was designated as Musli Glucomannan (MGM).
  • MGM Musli Glucomannan
  • the polysaccharide isolation may also start with hot water extraction or prior defatting of the tissue with chloroform-methanol (1:1 ratio).
  • DTH delayed type hypersensitivity model
  • Toxicological response evaluation (Single dose response) was carried out wherein normal Healthy mice (Mus musculus) were fed with a single oral dose of 2000mg/Kg body weight and observed for any abnormal symptoms. At this dose, the animals were normal and did not show any evident toxicity proving the safety for a single dose of 2000mg/Kg body weight.
  • toxicological response evaluation (repeated dose response)
  • normal Healthy mice (Mus musculus) were fed with a repeated oral dose of 100mg/Kg body weight for 28 days and observed for any abnormal symptoms. At this dose, all the animals were normal and did not exhibit any evident toxicity, proving the safety for repeated oral dose of 100mg/Kg body weight.
  • Chlorophytum carbohydrate substances(s) relates to all the parts of the whole plants and covers the polymeric substances including oligomeric glycans. These can be used individually or together in combination and same or similar or analogous constituents of different Chlorophytum species can be used individually or together.
  • the Chlorophytum or its substances embodied in the claims here can be used after pre-treatment or without pre-treatment.
  • Substances or mixtures of substances which can be obtained from any part of Chlorophytum can be used as such as contained in the herb or in pure or impure form. These active agents can be used individually or in combination as active agents or mixture of active agents. Mixtures of active substances can be obtained from the same Chlorophytum plant part or from different of the same species or a different species.
  • “Substances or mixtures of substances” according to the invention can consist of the same or of different representatives of the glycan class of chemical compounds. These chemical compounds can be used in natural form, i.e. unmodified by the obtaining process or modified by the obtaining process.
  • derivatives relate to all the compounds that can be derived from the compounds mentioned and can be achieved by chemical modification, attachment etc. For example, such derivatives can be formed by substitution, addition, esterification, saponification, condensation reactions, etc.
  • prevention relates to the broad use of Chlorophytum or substances or mixtures of substances obtained therefrom as a prophylaxis for the operational maintenance of immune-response apparatus in an individual without any clinically diagnosed disorder or prevention of the development of immuno-deficiency due to any physiological abnormality or immune system functionality, risking exposure to environment, infection or disease and treatment.
  • the formulations and products based on Chlorophytum and its substances as embodied in the claims may be optionally employed in a specific or combination 5 forms/ways/modes/carrier mediated/concentration pharmaceutically acceptable or physiologically compatible.
  • Purified means partially purified and/or completely purified. Therefore, a “purified” substance may be either partially purified or completely purified.
  • Extract means crude extract, purified extract, and purified composition obtained by purification of the extract.
  • Immuno-modulatory activity means means the ability of the substance to alter 0 immune status of the subject.
  • Test means the maximum dilution of the serum containing induced antibodies showing haemagglutination with the RBCs.
  • Serial Dilution is related to microplate format dilutions in series with dilution of serum by factors like 1, 2, 4, 8, 16, 32, 64, 128, 256, 512, 1024, 2048 etc.
  • Haemagglutination means visible agglutination in the form of serrated shield or button in a U-bottom microtiter plate.
  • Antigen means the rabbit RBCs used for induction of immunity in mice.
  • “Serum” means the supernant from the clotted blood.
  • Plant or part means either the the whole plant or any part of the the plant such as an 30 aerial part, seed, leaf, stem or roots or flower and any combination thereof.
  • the precipitates thus formed were collected by centrifugation at 5000 rpm for 10 min. at 4-10 0 C.
  • the precipitates were subjected to freeze drying to obtain a fluffy material or flakes (9.583 grams).
  • the polysaccharide fraction accounted for 38.3% of the tuber dry weight basis.
  • the substance or preparation finally obtained was freeze dried flake form of crude polysaccharide (designated as source Bio-RSI).
  • Example 3 The resultant precipitates were filtered out and dissolved in 100 ml of water (solution or gel form of the crude polysaccharides). The solution was diluted four times to yield the preparation with water extractable total polysaccharide at the concentration of 1 mg per ml. It was designated as Bio-RSIB and subjected to immunomodulatory activity (Example 7). ' Example 3
  • the filtrate (Pro-Bio- RSI D) was treated with 6% TCA (final concentration) to precipitate out proteins. Protein precipitates were removed by centrifugation (500Og for 10 minutes) and the supernatant (350ml) was subjected to ethanol precipitation to recover polysaccharides (partially purified water extractable easily water soluble fraction). The precipitates were collected by filteration and dissolved in 200 of ml water. This clear deproteinized polysaccharide solution (a concentration of 4mg/ml) was designated as Bio-RSID and employed to evaluate immunomodulatory activity. The preparation was also subjected to chemical compositional analysis (as in Example 5) and further purification through gel filteration chromatography (as in example 4).
  • Chlorophytum/Musli glucomannan (MGM) fraction of soluble polysaccharides was purified by molecular sieve exclusion chromatography through Sephacryl HR-200 column. For this, 0.5 ml aliquot of soluble polysaccharide was loaded on to a 38.5 x 1.4 cm column of Sephacryl HR-200 (void volume 17.5 ml) and the column was eluted with triple distilled water.
  • Fig. 1 Molecular exclusion chromatography of water extractable easily water soluble polysaccharide preparation of Chlorophytum borivillianum (Safed musli) through Sephacryl HR-200 column.
  • Detection of sugars was done by spraying the spray reagent comprising of diphenylamine (2% w/v), aniline (2% v/v), phosphoric acid (10% v/v) in ethanol.
  • the plate was heated at 110 0 C for 10 minutes and spots of authentic standards and sample hydrolysate were visualized and compared.
  • FIG. 1 Compositional analysis of Chlorophytum polysaccharides.
  • bioactive polymeric heteroglycan MGM of Chlorophytum/Safed Musli.
  • the bioactive polysaccharide substance is resourced in the plant as one of the major cellular component comprising as an example (without any limitation) 38 % (total) and 8% MGM and that compostional analysis method is TLC with authentic co-migration comparison with the development system of ethyl acetate: isopropyl alcohol: water: pyridine in the ratio of 26:14:8:2 (v/v)
  • Immunostimulant (humorral) activity in normal mice (Mus musculus) : Normal healthy outbred mice, maintained under standard conditions ( 22 ⁇ 3 0 C, 12:12 hr light : dark cycle, pellet diet and soaked Bengal gram), 5 animals in each group were taken for the experiment. The animals were fed with the test compound at the dose rate of 100mg/Kg body weight for a period of 1-28 days. Freshly collected and washed rabbit RBCs was used as an antigen which was used to immunize the animal on day 7 followed by the booster dose on day 14 th . Blood was collected from the orbital plexus after 21 days and assessed for haemaggluting (HA) titre.
  • HA haemaggluting
  • the haemagglutination was carried upon using a serial two fold dilution of the serum in 96 well 'U' bottom microtitre plates. The highest dilution showing visible agglutination was taken as the antibody titre. Results are represented in the following table (Table 1). Table 1: Haemagglutination titre of the animals treated.
  • DTH delayed type hypersensitivity model
  • Toxicological response evaluation Single dose response: Normal Healthy mice (Mus • musculiis) were fed with a single oral dose of 2000mg/Kg body weight and observed for any abnormal symptoms. At this dose, the animals were normal and did not show any evident toxicity proving the safety for a single dose of 2000mg/Kg body weight.
  • Toxicological response evaluation (repeated dose response): Normal Healthy mice (Mus musculus) were fed with a repeated oral dose of lOOmg/Kg body weight for 28 days and observed for any abnormal symptoms. At this dose, all the animals were 20 normal and did not exhibit any evident toxicity, proving the safety for repeated oral dose of 100mg/Kg body weight.
  • bioactive non-nutrient polysaccharide underlines the 30 multiferous uses of the congener plant/plant part as a functional food for weight loss, lower glycemic food ingredient with added advantage of immunity against disease development/combating. 3. It provides Chlorophytum as an alternative to Konjac for food, nutraceutical and medicinal purposes. 4. It provides the multiferous uses of the plant as a value additive ingredient in foods, food recipies, cuisines, restaurants etc. 5. It can be used a thickening agent or otherwise calorie discounted additive agent in foods, snacks, chocolates, soups, jams, icecreams, jellies etc. with attendant health gains and avoiding calorie gains. 6.
  • the pharmaceutical compositions with crude or enriched polysaccharides can be used as immune strengthening/disease resistance safe herbal prescriptions.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Alternative & Traditional Medicine (AREA)
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  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
EP07734177A 2006-04-04 2007-04-03 Pharmazeutische zusammensetzung als immunomodulierendes mittel und verfahren zu ihrer herstellung Withdrawn EP2010197A2 (de)

Applications Claiming Priority (2)

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IN954DE2006 2006-04-04
PCT/IB2007/000856 WO2007113646A2 (en) 2006-04-04 2007-04-03 A pharmaceutical composition useful as an immunomodulating agent and a process for the preparation thereof

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