EP1169047A1 - Compositions and methods for treatment of diabetes - Google Patents
Compositions and methods for treatment of diabetesInfo
- Publication number
- EP1169047A1 EP1169047A1 EP00921679A EP00921679A EP1169047A1 EP 1169047 A1 EP1169047 A1 EP 1169047A1 EP 00921679 A EP00921679 A EP 00921679A EP 00921679 A EP00921679 A EP 00921679A EP 1169047 A1 EP1169047 A1 EP 1169047A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- insulin
- diabetes
- cells
- brickellia
- treatment
- 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- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
-
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5085—Supracellular entities, e.g. tissue, organisms of invertebrates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
Definitions
- the present application concerns the field of natural products and more specifically plant extracts and compounds useful for the treatment of diabetes.
- Diabetes mellitus a potentially devastating, complex disorder of glucose metabolism, which is currently partially controllable by insulin injections and/or drugs, is increasing in worldwide frequency.
- diabetes In the United States over ten million persons are estimated to have diabetes.
- the financial cost is in the many billions of dollars reflecting treatment expense and loss of productivity while the human cost in impaired function, progression to blindness, limb amputations, kidney failure and heart and vascular disease is immeasurable.
- Type I or Juvenile Onset Insulin Dependant Diabetes Mellitus
- Type II or Adult Onset Non-insulin Dependant Diabetes Mellitus
- IDDM is an immune modulated version of the disease in which insulin production is impaired whereas NDDM is a disorder in which the cells fail to respond to insulin. Diabetes is recognized in the ancient literature of Egypt, China, and India.
- the simple sugar glucose is a primary energy source for human cells
- Glucose is required for optimal growth, development, and for maintenance of the central nervous system.
- the brain is an avid consumer of glucose such that any significant lowering of blood glucose results in a concomitant drop in the glucose level in the brain with resulting cessation of normal brain function (coma).
- the entry of glucose into the cells and the metabolism of the glucose within the cells are critical to sustain life in the human body.
- Insulin a regulatory transport hormone, controls the uptake and transport of glucose into the cells either for energy production or for storage therein.
- Glucose enters the bloodstream from the digestive system.
- the intracellular level of glucose is too low or the blood level of glucose is too high, insulin is released to mediate the uptake of glucose by the cells for metabolism or storage, respectively.
- the blood level of glucose is too low, other hormones mediate the release of glucose from glycogen (a starch-like storage polymer).
- glycogen a starch-like storage polymer
- insulin is necessary for the glucose homeostasis found in proper body metabolism.
- the proper concentration of insulin in the blood is critical. A lack of insulin leads to coma and death from metabolic problems caused by excessive blood sugar. On the other hand, an excess of insulin results in shock caused by excessively low blood sugar. Similarly, if the cells fail to respond properly to insulin, the homeostasis is disrupted and excessive blood sugar levels result.
- Insulin is produced within the pancreas by 1.5 million beta cells located in clusters known as the Islets of Langerhans. Insulin is a moderate sized protein composed of two chains: an alpha chain of 21 amino acids and a beta chain of 30 amino acids linked to one another by disulfide bonds.
- Such beta cell destruction is recognized as being due to attack by several types of immune cells including NK (natural killer) cells and double negative (CD4-[W3/25+OX19+]/ CD8- [OX8+OX19+]) T-Lymphocytes.
- the autoimmune response results in macrophage activation by the double negative T-cells, wherein activated macrophages then attack body cells.
- double negative T-cells escape and become potentially autoreactive clones.
- the CD8 protein expressed by the majority of NK cells, can be modulated by administration of monoclonal antibodies to reduce the incidence of diabetes.
- the administration of poly clonal antibodies directed towards the NK cell glycolipid AGMI also prevents autoimmune Islet destruction.
- aldosterone from the adrenal cortex, sets in motion a set of reactions at the surface of all cells of body tissues to regulate the uptake and retention of sodium and to extrude potassium.
- Lowered serum sodium and the high serum potassium levels enhance aldosterone secretion.
- the adrenal glands are influenced by the neurotransmitter dopamine, an adrenal suppressor and by the neurotransmitter seratonin, an adrenal stimulator; low potassium levels impact dopamine production and, therefore, alter aldosterone and cortisol secretion.
- other factors are involved in the negative feedback of pituitary corticotropin to cortisol.
- Atrial natriuretic peptides or sodium excreting hormones, that inhibit secretion of aldosterone, sodium chloride, potassium, and phosphorous. It has also been recognized that there is an interference with the ongoing inhibition of prolactin by dopamine from the hypothalamus as can be seen during the invasion of the pituitary stalk by pineal tumors. These factors may be involved in the immune abnormalities leading to insulin dependent diabetes or in the abnormal insulin responses of insulin independent diabetes.
- Insulin like growth factor I (RGF-I) , is a mitogenic polypeptide that regulates cell cycle progression. IGF- I and insulin are heterotetrameric proteins that possess intrinsic tyrosine kinase activity. IGF-I actions are dependent upon binding to its own specific cell surface receptors. Both insulin and IGF-I activate insulin receptor substrate -I(IRS-l), an important multisite docking protein implicated in mytogenic signaling.
- Activation of mytogenic pathways is magnified as a consequence of mutations in the K-ras oncogene and cell cycle associated kinases, such as pl6.
- Insulin exerts mytogenic effects on cells by activating -the IGF-I receptor, which leads to phosphorylation of IRS-1, an important regulatory protein that mediates the growth promoting effects of insulin.
- the tyrosine kinases are thought to be truncating the sequence of production of dopamine so that a post receptor defect is caused which has no affinity for the necessary glucocorticoid, but has affinity for the DN T-cell CD4- and CD8- proteins.
- proteoglycin to rebalance the K+ (potassium) channel to allow a gate voltage to buildup and permit secretion of adequate amounts of aldosterone. It was also believed that a valance corrected aggregated series of polypeptides assimilated into a proteoglycan would accomplish this result.
- Diabetes is considered to be insidious, since there is no cure known at this time.
- Various treatments have been used to ameliorate diabetes.
- dietetic measures have been employed to balance the relative amounts of proteins, fats, and carbohydrates in a patient.
- diabetic conditions of moderate or severe intensity are treated by the administration of insulin.
- prescription drugs such as "Glucoside” have been employed to rejuvenate impaired insulin production in adult onset diabetics.
- Other drugs are used to modulate the effectiveness of insulin.
- treatment of diabetes of either juvenile or adult onset types, have achieved only partial success.
- a novel and useful composition for treating diabetes utilizes a steam or aqueous extract of a plant known as Brickellia californica.
- the plant is gathered, dried, and combined with boiling water. The extract is then taken orally by a patient on a periodic basis.
- the genus Brickellia is known to be rich in flavonoids and other secondary plant products.
- the genus is large and many species are mentioned in folk medicine including, besides B. californica-, B. ambigens, B. arguta, B. brachyphylla, B. cylindracea, B. eupatoriodes, B. glutinosa, B. grandiflora, B. laciniata, B. lemmonii, B. oblongifolia, and B. veronicaefolia.
- Other species of the genus appear to have some or all of the active components of B. californica.
- Brickellia californica live plants were located and harvested.
- Brickellia is a small to mid-sized shrub with relatively small, lobed leaves.
- Approximately four sprigs of leaves and stems were cut from the harvested plants. Each sprig was approximately -3 inches in length.
- the sprigs were placed in one half gallon of water and heated until boiling. Boiling continued for five minutes at which time, the extract was decanted from the container and cooled. The color of the decanted liquid was light brown.
- the cooled extract from the Brickellia californica sprigs was administered to four adult human males ranging from 30 to 40 years of age. Each of the males suffered from diabetes. The dosage to each subject was four to five glasses per day of the extract.
- Live Brickellia californica plants were harvested and dried.
- the dried plant material was macerated using a mortar and pestle, transferred into a 125 ml Erlenmeyer flask and extracted with a mixture of chloroform and methanol in a ratio of 1: 1.
- the mixture was stirred for four hours with a magnetic stirrer.
- the extract from the flask was then filtered to remove cellulosic debris and concentrated in a "rotavap" under a vacuum to yield a crude gummy residue.
- the residue was partitioned in chloroform and methanol to yield to two fractions labeled CHC1 3 (the more hydrophobic chloroform soluble fraction) and MeOH (the more hydrophilic methanol soluble fraction).
- the CHC1 3 and MeOH fractions were analyzed using a Hewlett Packard 6890 gas chromatograph-mass spectrometer (GC-MS) fitted with an HP-5MS capillary column (30 meters x 250 ⁇ m x 0.25 ⁇ m).
- the analysis conditions were as follows: initial temperature was 125 °C which was held for five minutes, followed by an increase to 275 °C at a rate of 10 °C per minute with the final temperature of 275 °C being held 15 minutes.
- the analysis by the GC-MS of CHC1 3 fraction demonstrated the presence of a group of polar flavonoids with retention times in the range of 13-15 minutes, the presence of a group of sesquiterpenes with retention times between 16-18 minutes, and a small group of aliphatic hydrocarbons with retention times between 20- 25 minutes.
- Analysis by GC-MS of the MeOH fraction produced similar results except that the MeOH fraction was largely free of the aliphatic hydrocarbons. It is believed that the Brickellia californica extract includes the flavonoids dihydroxykaemferol, apigenin, luteolin, myricetin and quercetin.
- Brickellia contains these, or similar flavonoids, albeit in different proportions, and should also be effective in treatment of diabetes.
- Experiments with diabetic test animals (rats and mice) were carried out.
- the Brickellia extract was effective in controlling blood glucose in these model systems.
- the administration of synthetic versions of the Brickellia flavonoids were also effective at lowering glucose levels.
- luteolin was the most effective agent.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Toxicology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12782499P | 1999-04-05 | 1999-04-05 | |
US127824P | 1999-04-05 | ||
PCT/US2000/008957 WO2000059522A1 (en) | 1999-04-05 | 2000-04-04 | Compositions and methods for treatment of diabetes |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1169047A1 true EP1169047A1 (en) | 2002-01-09 |
Family
ID=22432145
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00921679A Withdrawn EP1169047A1 (en) | 1999-04-05 | 2000-04-04 | Compositions and methods for treatment of diabetes |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1169047A1 (en) |
JP (1) | JP2002541116A (en) |
AU (1) | AU780233B2 (en) |
BR (1) | BR0009592A (en) |
CA (1) | CA2368215A1 (en) |
MX (1) | MXPA01010037A (en) |
WO (1) | WO2000059522A1 (en) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020068704A1 (en) * | 1999-04-05 | 2002-06-06 | Ziegler Randy H. | Compositions and methods for treatment of diabetes |
US6555573B2 (en) | 2000-12-21 | 2003-04-29 | The Quigley Corporation | Method and composition for the topical treatment of diabetic neuropathy |
ATE456957T1 (en) * | 2000-12-21 | 2010-02-15 | The Quigley Corp | METHOD AND COMPOSITION FOR TREATING DIABETIC NEUROPATHY |
MXPA04002077A (en) * | 2001-09-06 | 2005-02-17 | Synorx Inc | Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto. |
EP1501520A1 (en) | 2002-05-06 | 2005-02-02 | Diakron Pharmaceuticals, Inc. | Pharmaceutical compositions for lowering blood glucose and blood cholesterol levels |
US7083813B2 (en) | 2002-11-06 | 2006-08-01 | The Quigley Corporation | Methods for the treatment of peripheral neural and vascular ailments |
AU2004312072B2 (en) | 2003-12-29 | 2011-06-23 | President And Fellows Of Harvard College | Compositions for treating or preventing obesity and insulin resistance disorders |
US8017634B2 (en) * | 2003-12-29 | 2011-09-13 | President And Fellows Of Harvard College | Compositions for treating obesity and insulin resistance disorders |
WO2006138418A2 (en) | 2005-06-14 | 2006-12-28 | President And Fellows Of Harvard College | Improvement of cognitive performance with sirtuin activators |
JP2008007452A (en) * | 2006-06-28 | 2008-01-17 | Ajinomoto Co Inc | PANCREAS beta CELL PROTECTANT |
US8287677B2 (en) | 2008-01-31 | 2012-10-16 | Kimberly-Clark Worldwide, Inc. | Printable elastic composite |
JP5594719B2 (en) * | 2010-01-06 | 2014-09-24 | 国立大学法人神戸大学 | Muscle sugar uptake promoter |
-
2000
- 2000-04-04 MX MXPA01010037A patent/MXPA01010037A/en not_active Application Discontinuation
- 2000-04-04 BR BR0009592-3A patent/BR0009592A/en not_active IP Right Cessation
- 2000-04-04 JP JP2000609085A patent/JP2002541116A/en active Pending
- 2000-04-04 AU AU41964/00A patent/AU780233B2/en not_active Ceased
- 2000-04-04 EP EP00921679A patent/EP1169047A1/en not_active Withdrawn
- 2000-04-04 CA CA002368215A patent/CA2368215A1/en not_active Abandoned
- 2000-04-04 WO PCT/US2000/008957 patent/WO2000059522A1/en active Search and Examination
Non-Patent Citations (1)
Title |
---|
See references of WO0059522A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO2000059522A1 (en) | 2000-10-12 |
AU780233B2 (en) | 2005-03-10 |
BR0009592A (en) | 2002-01-08 |
AU4196400A (en) | 2000-10-23 |
CA2368215A1 (en) | 2000-10-12 |
MXPA01010037A (en) | 2003-07-14 |
JP2002541116A (en) | 2002-12-03 |
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RIC1 | Information provided on ipc code assigned before grant |
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Free format text: COMPOSITION COMPRISING AN AQUEOUS EXTRACT OF BRICKELLIA FOR TREATMENT OF DIABETES |
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Effective date: 20081007 |