WO2002032436A1 - Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients - Google Patents
Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients Download PDFInfo
- Publication number
- WO2002032436A1 WO2002032436A1 PCT/IN2000/000106 IN0000106W WO0232436A1 WO 2002032436 A1 WO2002032436 A1 WO 2002032436A1 IN 0000106 W IN0000106 W IN 0000106W WO 0232436 A1 WO0232436 A1 WO 0232436A1
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- WIPO (PCT)
- Prior art keywords
- composition
- cow urine
- distillate
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- cow
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/22—Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- BIOACTIVE FRACTION FROM COW URINE DISTILLATE (' GO- MUTRA') AS A BIO-ENHANCER OF ANTI-INFECTIVE, ANTI-CANCER AGENTS AND NUTRIENTS
- the invention relates to an absolutely novel use of cow urine distillate as activity enhancer and availability facilitator for bioactive molecules including anti-infective and anti-cancer agents.
- bioactive molecules e.g. antibiotics, drugs, nutraceuticals, cardiovascular, hepatoprotective, neuro-tonics etc.
- the present invention has direct implication in drastically reducing the dosage of antibiotics, drugs and anti-cancer agent while increasing the efficiency of absorption of bioactive molecules.
- the novelty of the invention lies in the fact revealed through precise experimentation that the enhancement action and its effectiveness is achievable only in the range of concentration which is literally in nano to micro molar levels. And when a higher concentration / dosage is used in the formulation or combinations the activity(ies) do not appear.
- the present invention was the result of planned experiments to provide a novel method for improving activity and bioavailability of antibiotics, drugs and other molecules using 'cow urine distillate' in different formulations.
- compositions and methods of the invention are also intended to be used in agriculture and veterinary practice.
- Cow's urine can be considered as the most effective animal origin substance/secretion with the capacity of general health improvement but it does need substantiation through scientific experimentation.
- the applicants considered it worthwhile to scientifically look at this and define the molecular basis of the values through in vitro and in vivo assays.
- the applicants in the first instance probed whether it contained any drug facilitator elements since such a property would make it a highly useful natural substance.
- use of 'piperine' as a bioavailability enhancer has been described (United States Patents 5,616,593 and 5,972,382). Till today thus, the known bioavailability enhancer documented is piperine and a series of inventions related to this compound have been described in the following prior arts.
- the main objective is to provide new use of the bio- active fraction as a bio-enhancer and as a bioavailability facilitator.
- In another objective of the invention is to provide method for improving activity and bioavailability of antibiotics, drugs and other molecules using active fraction from cow urine distillate.
- Still another objective of the invention is to provide a process for the extraction of the active fraction form the cow urine.
- the invention relates to new use of a known abundantly available cow urine distillate as an enhancer of antibiotic action on the target.
- the molecule of invention helps in the absorption of antibiotics across the cell membrane in animal cells, gram positive and gram negative bacteria. Similar activities can also be obtained by using the distillate of the urine of cow at 40-50°C and from the concentrate, which is lyophilized and dissolved for further use. Further the urine distillate from buffalo, camel, deer provides similar activity of bioavailability.
- Fig.1 represents HPLC characters of cow urine (Go-mutra) distillate
- a pharmaceutical composition comprising an effective amount of cow urine distillate as a bioavailability facilitator and a pharmaceutically acceptable additives selected from anticancer compounds, antibiotics, drugs, therapeutic and nutraceutic agents, ions and similar molecules which are targeted to the living systems.
- cow urine distillate is used as bioavailability facilitator for anticancer therapy directly or in combination with anticancer molecules.
- the cow urine distillate is used in antifungal therapy for fungal infections.
- the antifungals are azoles, clotrimazole, mystatin, amphotericin and similar materials.
- fungi covering infections are mycetial, Candida, yeast or other fungicidal compounds.
- cow urine distillate is used in TB therapy including multi drug resistant tuberculosis in combination with isoniazid and other anti-tubercular agents.
- the bioavailability facilitator helps in transferring the compound across the membrane and for better effectivity on the target site.
- the antibiotics are Quinolones, fluoroquinolones like Nalidixic acid and others like Rifampicin, Tetracycline, ampicillin and similar compounds.
- the antibiotics, ions and similar compounds are isoniazid and hydrogen peroxide.
- the bioavailability facilitator helps the antibiotics and other molecules to act better on the target by increasing the effectivity.
- the living system may be bacteria, fungi or any living cells.
- the anti bacterial agents are selected from the group comprising Quinolones, Rifampicin, Tetracycline and ampicillin.
- cow urine (Go-mutra) distillate is in the range between
- the lyophilized active fraction used is in the range between 0.1 ⁇ g/ml to 100 ⁇ g/ml.
- the bioactive fraction enhances the activity of anti-bacterial agents, anti-cancer agents and anti-tuberculosis agents from 2 to 80 folds.
- the bioactive fraction enhances the activity of anti-bacterial agents from 2 to 80 folds.
- the anti bacterial agent is an anti-tuberculosis agent selected from isoniazid, pyrazinamide and other similar compounds.
- the bioactive fraction enhances the activity of anti- tuberculosis agents from 2 to 20 folds.
- the anti-cancer agent is selected from group consisting of Paclitaxel (Taxol).
- the bioactive fraction enhances the activity of anti-cancer agents from 2 to 20 folds.
- the methodology followed by us for this screening included specifically designed bioassays as described below.
- the bacterial and fungal strains used in this invention were acquired commercially from Institute of Microbial Technology (IMTECH), Chandigarh which possessed corresponding properties of the ATCC strain mentioned.
- Assay for bio-enhancement of anti-infective agents a) The minimum inhibitory concentration (MIC) of antibiotic is determined against Escherichia coli (equivalent of ATCC 10536), Bacillus subtilis (equivalent of ATCC 6015) and Mycobacterium smegmatis (equivalent of ATCC 10231) in broth and disc diffusion assay. b) The antibiotics agents at concentrations 1/4, 1/3, 1/2 and equal to MIC are added alone and in combination with the test compound at varying concentrations on disc and in broth to evaluate the comparative inhibition. c) These combination showing significant advantage or higher activity than antibiotic alone in terms of enhanced inhibition of bacterial growth (large inhibition zone in disc diffusion and affectivity of lower concentration in broth assay) are picked up for future testing.
- MIC minimum inhibitory concentration
- MCF-7 Breast cancer commercial cell line obtained from National Center for Cell Sciences (NCCS), Pune
- NCCS National Center for Cell Sciences
- a) MCF-7 Breast cancer commercial cell line obtained from National Center for Cell Sciences (NCCS), Pune
- NCCS National Center for Cell Sciences
- the test component (s) is added at desired concentrations in different wells just after the medium replacement.
- the medium is removed from the wells, ii.
- the wells are rinsed with 1ml PBS (Phosphate buffer saline), iii.
- MEM Minimum Essential Medium
- Penicillin G 10 mg Streptomycin 20 mg Gentamycin 5 mg Foetal Calf Serum 15 ml Foetal Calf Serum 15 ml Distilled water 85 ml
- Example 1 Cow urine distillate mediated enhancement in the killing action of antibiotics against Gram-negative bacterium Escherichia coli. Table 1:
- Example 2 Cow urine distillate mediated enhancement in the killing action of antibiotics against Gram-positive bacterium Bacillus subtilis.
- Example 4 Cow urine distillate mediated enhancement in the killing action of izoniazid and hydrogen peroxide against oxyR mutant of bacterium Escherichia coli.
- the cow urine distillate concentration is 0.001 ⁇ l/ml Table 4:
- the oxyR gene is required for the induction of a regulon of hydrogen peroxide-inducible genes in Escherichia coli (Christman M F, Storz G and Ames BN (1989)
- Oxy R a positive regulator of hydrogen peroxide-inducible genes in Escherichia coli and Salmonella typhimurium, is homologous to a family of bacterial regulatory proteins (Proc. Natl. Acad. Sci. (USA). 86:3484-3488.).
- the mutants of these genes are sensitive to drugs like isoniazid and hydrogen peroxide, which produce free radicals, damaging the cellular systems. So the killing activities of these compounds are increased by 5 to 8 folds by cow urine.
- Example 5 Cow urine distillate mediated enhancement in the activity of anti cancerous compounds.
- the cow urine distillate concentration is 1 ⁇ l/ml
- Example 6 Bioenhancement of antifungal agent clotrimazol by bioactive Fraction Gm-IV. The concentration of the active fraction is kept at 10 ⁇ g/ml.
- cow urine distillate enhances the transport of antibiotics e.g. Rifampicin, Tetracycline, Ampicillin across the gut as well as artificial membrane.
- antibiotics e.g. Rifampicin, Tetracycline, Ampicillin across the gut as well as artificial membrane.
- the enhancement in transport is approximately 2 to 7 folds.
- Step 1 Cow urine is collected aseptically in the stainless steel container directly from the cow, which is maintained in hygienic environment
- Step 2 Fifteen liters of cow urine is distilled continuously at 40 - 50 °C in glass distillation apparatus to obtain 10 - 12 liters of the distillate in 16 to 18 hours.
- Step 3 The distillate is packed in surface sterilized plastic or glass container for further use
- Step 4 200 ml of cow urine distillate was mixed with half the volume of methanol and extracted with hexane.
- Step 5 The hexane fraction (Gm-I) was lyophilized and tested for similar activity as that of cow urine (Go-mutra).
- Step 6 The aqueous fraction was extracted with ethyl acetate and the ethyl acetate fraction (Gm-II) was lyophilized and tested for similar activity as that of cow urine (Go-mutra).
- Step 7 Further, aqueous fraction containing white precipitate was extracted with butanol and the butanol fraction (Gm-IH) having pale yellow precipitate was lyophilized and tested for similar activity as that of cow urine (Go-mutra).
- Step 8 The remaining aqueous fraction containing white crystalline precipitate (Gm-IV) was dried and tested for similar activity as that of cow urine (Go-mutra). .
- the novelty of the invention lies in the fact revealed through precise experimentation that the enhancement action and its effectiveness is achievable only in the range of concentration which is literally in nano to micro molar levels. And when a higher concentration / dosage is used in the formulation or combinations the activity(ies) do not appear.
- Physical characters of the Gm-IV fraction Color White
- Solubility Water-soluble and mixture containing water
- HPLC was performed on LC-8A Shimadzu HPLC with mobile phase water: acetonitrile (80:20), flow rate l.Oml/min, UN detection at 275 nm and C-18 E MERCK (150 X 4 mm) column. Two major peaks (retention time 5.334 and 11.310 min) observed in the profile of cow urine (Go-mutra) distillate ( Figure 1).
- the fraction Gm-IV also enhances the transport of antibiotics and vitamins across the mammalian gut membrane.
- the example describing the enhanced transport of rifampicin by the fraction Gm-IV is given below.
- Example 8 Fraction Gm-IV of cow urine (Go-mutra) distillate mediated enhancement in the bioavailability across the biological membrane (Rifampicin, lmg/ml and fraction Gm- IV, l.O ⁇ g/ml). Table 7:
- the enhancing activity of the lyophilized product of the invention is found to have same enhancing activity like that of the distillate.
- the sample shows enhancement of bioavailability of rifampicin (antibiotic) and Vitamin B-12 across the mammalian gut membrane (Goat intestine was used) within 2 hours and it keeps increasing upto 4 hours.
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Abstract
Description
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Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT00990873T ATE273014T1 (en) | 2000-10-20 | 2000-10-20 | USE OF THE BIOACTIVE FRACTION FROM THE COW'S URINE DISTILLATE (ßGO MUTRAß) TO INCREASE THE EFFECTIVENESS OF ANTI-INFECTIVES, ANTI-CANCER AND NUTRITIONAL PRODUCTS |
AU3048601A AU3048601A (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
CNB2005101140471A CN100536856C (en) | 2000-10-20 | 2000-10-20 | Use of bioactive composition derived from cattle urine distillate ('Go-mutra') as anti-infective,anti-tumour and biological intensifier of nutriment |
DE60012996T DE60012996T2 (en) | 2000-10-20 | 2000-10-20 | USE OF THE BIOACTIVE FRACTION FROM THE CROWN ("GO MUTRA") FOR INCREASING THE EFFICACY OF ANTI-INFECTIVA, ANTI-CANCER AND NUTRITIONAL AGENTS |
CA2425025A CA2425025C (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
MXPA03002653A MXPA03002653A (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ( go mutra ) as a bio-enhancer of anti-infective, anti-cancer agents and nutrients. |
DK00990873T DK1330253T3 (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction of courine distillate ("Go-mutra") as a bio-promoter for anti-infectives, anticancer agents and foods |
AU2001230486A AU2001230486B2 (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
EP00990873A EP1330253B1 (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
KR1020037004325A KR100848394B1 (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate '??-?????' as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
CNB008199183A CN1234372C (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('Go-mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
BR0017342-8A BR0017342A (en) | 2000-10-20 | 2000-10-20 | Use of cow urine distillate bioactive fraction (go-mutra) as a bio-intensifier of anti-infectious, anticancer and nutrient agents |
PCT/IN2000/000106 WO2002032436A1 (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
AU2005237162A AU2005237162B2 (en) | 2000-10-20 | 2005-11-25 | Pharmaceutical composition containing cow urine distillate and an antibiotic |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IN2000/000106 WO2002032436A1 (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
Publications (1)
Publication Number | Publication Date |
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WO2002032436A1 true WO2002032436A1 (en) | 2002-04-25 |
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PCT/IN2000/000106 WO2002032436A1 (en) | 2000-10-20 | 2000-10-20 | Use of bioactive fraction from cow urine distillate ('go mutra') as a bio-enhancer of anti-infective, anti-cancer agents and nutrients |
Country Status (11)
Country | Link |
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EP (1) | EP1330253B1 (en) |
KR (1) | KR100848394B1 (en) |
CN (2) | CN100536856C (en) |
AT (1) | ATE273014T1 (en) |
AU (3) | AU3048601A (en) |
BR (1) | BR0017342A (en) |
CA (1) | CA2425025C (en) |
DE (1) | DE60012996T2 (en) |
DK (1) | DK1330253T3 (en) |
MX (1) | MXPA03002653A (en) |
WO (1) | WO2002032436A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004087176A1 (en) * | 2003-03-31 | 2004-10-14 | Council Of Scientific And Industrial Research | A composition (rucd) for protecting and/or repairing dna from oxidative damages and a method thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3248295A (en) * | 1962-12-26 | 1966-04-26 | Canadian Patents Dev | Anti-allergic urine extract and method of making same |
Family Cites Families (1)
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KR100523463B1 (en) * | 2003-05-30 | 2005-10-25 | 영남대학교 산학협력단 | Composition comprising the extract of Astilbe rubra or Astilbic acid and Peltoboykinolic acid derivatives having anti-inflammatory or anti-allergic activity |
-
2000
- 2000-10-20 WO PCT/IN2000/000106 patent/WO2002032436A1/en active IP Right Grant
- 2000-10-20 MX MXPA03002653A patent/MXPA03002653A/en active IP Right Grant
- 2000-10-20 AU AU3048601A patent/AU3048601A/en active Pending
- 2000-10-20 CN CNB2005101140471A patent/CN100536856C/en not_active Expired - Fee Related
- 2000-10-20 AU AU2001230486A patent/AU2001230486B2/en not_active Ceased
- 2000-10-20 AT AT00990873T patent/ATE273014T1/en not_active IP Right Cessation
- 2000-10-20 KR KR1020037004325A patent/KR100848394B1/en not_active IP Right Cessation
- 2000-10-20 CN CNB008199183A patent/CN1234372C/en not_active Expired - Fee Related
- 2000-10-20 DK DK00990873T patent/DK1330253T3/en active
- 2000-10-20 EP EP00990873A patent/EP1330253B1/en not_active Expired - Lifetime
- 2000-10-20 BR BR0017342-8A patent/BR0017342A/en not_active IP Right Cessation
- 2000-10-20 DE DE60012996T patent/DE60012996T2/en not_active Expired - Lifetime
- 2000-10-20 CA CA2425025A patent/CA2425025C/en not_active Expired - Fee Related
-
2005
- 2005-11-25 AU AU2005237162A patent/AU2005237162B2/en not_active Ceased
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3248295A (en) * | 1962-12-26 | 1966-04-26 | Canadian Patents Dev | Anti-allergic urine extract and method of making same |
Non-Patent Citations (3)
Title |
---|
CHEMICAL ABSTRACTS, vol. 121, no. 7, 1994, Columbus, Ohio, US; abstract no. 74040b, page 142; XP002167367 * |
OLUSI S O ET AL: "EVIDENCE FOR COMPLEMENT ACTIVATION FOLLOWING THE ORAL ADMINISTRATION OF COWS URINE CONCOCTION IN RATS.", AFR J MED MED SCI, (1978) 7 (2), 79-84., XP000996728 * |
VAN GINKEL L.A. ET AL: "The certification of the individual stilbene mass concentrations in lyophilized bovine urine CRMs", COMM. EUR. COMMUNITIES, vol. EUR15027, 1994, pages eur * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004087176A1 (en) * | 2003-03-31 | 2004-10-14 | Council Of Scientific And Industrial Research | A composition (rucd) for protecting and/or repairing dna from oxidative damages and a method thereof |
Also Published As
Publication number | Publication date |
---|---|
KR100848394B1 (en) | 2008-07-24 |
DE60012996T2 (en) | 2005-01-27 |
AU2005237162A1 (en) | 2005-12-22 |
DE60012996D1 (en) | 2004-09-16 |
ATE273014T1 (en) | 2004-08-15 |
MXPA03002653A (en) | 2004-01-29 |
CN100536856C (en) | 2009-09-09 |
KR20040015010A (en) | 2004-02-18 |
BR0017342A (en) | 2004-02-03 |
CA2425025A1 (en) | 2002-04-25 |
AU3048601A (en) | 2002-04-29 |
CN1788735A (en) | 2006-06-21 |
EP1330253B1 (en) | 2004-08-11 |
CN1454092A (en) | 2003-11-05 |
DK1330253T3 (en) | 2004-10-04 |
CA2425025C (en) | 2010-11-23 |
AU2005237162B2 (en) | 2007-02-08 |
EP1330253A1 (en) | 2003-07-30 |
AU2001230486B2 (en) | 2005-11-10 |
CN1234372C (en) | 2006-01-04 |
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