WO2008000063A1 - Produit à base de plantes comprenant de la cannelle et de la margose pour traiter le diabète - Google Patents

Produit à base de plantes comprenant de la cannelle et de la margose pour traiter le diabète Download PDF

Info

Publication number
WO2008000063A1
WO2008000063A1 PCT/CA2007/001066 CA2007001066W WO2008000063A1 WO 2008000063 A1 WO2008000063 A1 WO 2008000063A1 CA 2007001066 W CA2007001066 W CA 2007001066W WO 2008000063 A1 WO2008000063 A1 WO 2008000063A1
Authority
WO
WIPO (PCT)
Prior art keywords
pubmed
pmid
medline
indexed
cinnamon
Prior art date
Application number
PCT/CA2007/001066
Other languages
English (en)
Inventor
David Solomon
Philip Maurice Lapointe
Original Assignee
Innovative Life Sciences Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Innovative Life Sciences Corporation filed Critical Innovative Life Sciences Corporation
Publication of WO2008000063A1 publication Critical patent/WO2008000063A1/fr

Links

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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/42—Cucurbitaceae (Cucumber family)
    • 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)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin

Definitions

  • This invention relates to a new herbal product and in particular, to a new herbal product comprising cinnamon (Cinnamomi cassiae: Cinnamonum verum) and bitter melon (Momordica charantia).
  • cinnamon Cinnamomi cassiae: Cinnamonum verum
  • bitter melon Memordica charantia
  • CVD cardiovascular disease
  • metabolic syndrome also known as insulin resistance syndrome, or syndrome X
  • syndrome X insulin resistance syndrome
  • bitter melon has been widely used for centuries, and is a traditional folk herb for diabetes mellitus in Russia, China and Korea. It is also thought to possess anti- fever and antibiotic properties, as well as being as mild analgesic and sedative.
  • cinnamon supplementation was its antioxidant capacity, due to its phenolic acids and flavonoids.
  • This antioxidant capacity may not only slow the progression of Type 2 diabetes complications, by quenching the excessive oxygen free radical damage seen in diabetes, it may also protect LDL cholesterol from oxidation, reducing the likelihood of it being scavenged and incorporated into blood vessel wall plaque, the latter being a major part of atherosclerosis, hypertension and CVD.
  • this new therapeutic formulation may be used to treat diabetes and CVD, and also in the precursor syndrome, where almost all of the characteristics of this syndrome - high total and LDL cholesterol, high triglyceride, low HDL cholesterol, borderline high blood glucose levels, obesity and high waist circumference - may be improved. Even borderline high blood pressure, which is normally affected by the degree of obesity, may be reduced. In effect, this therapeutic formulation will reduce the incidence of metabolic syndrome, which, in turn, would reduce the incidence of diabetes, CVD and obesity. This is the first herbal combination with the potential to have more significant effects than pharmaceutical drugs on this triumvirate of conditions which continues to have a major impact on the health of North Americans.
  • the present invention provides a novel therapeutic formulation which comprises cinnamon and bitter melon.
  • a further object of the present invention is to provide a new therapeutic formulation which comprises cinnamon and bitter melon in a ratio of seventy: thirty (70:30).
  • the two active ingredients of the new therapeutic formulation are cinnamon and bitter melon. Both the plants are known to have hypoglycaemic properties in traditional Chinese, Indian and Caribbean Medicine. [00012] In recent years numerous laboratory and clinical studies have been conducted on these two plants by biological scientists, pharmacologists and pharmacists at prestigious research centres like Department of Pharmacy at the Kings College of London, University of California, Santa Barbara, Iowa State University and the U.S. Department of Agriculture. All of these studies show findings that confirm the therapeutic properties of the plants claimed by the traditional medicine and some of the research actually is considered to be break through in the field of natural health products. At USDA, scientists have been able to identify the particular molecule in cinnamon that mimics insulin and is responsible for its hypoglycaemic properties. [00013] The new therapeutic formulation contains cinnamon and bitter melon at a ratio of
  • Diabetes is a potent risk factor for cardiovascular disease as it not only affecting glucose metabolism but also influences lipid metabolism (Jayasooriya et al. 2000). Diabetes is divided into two major categories: type 1 diabetes, previously known as insulin dependent diabetes mellitus (IDDM), and type 2 diabetes, previously known as non-insulin dependent diabetes mellitus (NIDDM). Although the recommended treatments for these two categories are usually somewhat different, insulin for IDDM and lifestyle management for NIDDM, the overall result is improving glucose homeostasis. Lifestyle management such as changes in diet and an exercise regimen continues to be essential and effective but it may be insufficient or difficult for patient compliance rendering conventional drug therapies useful (Dey et al. 2002).
  • IDDM insulin dependent diabetes mellitus
  • NIDDM non-insulin dependent diabetes mellitus
  • Cinnamomum aromaticum (sp. Cassia) is from the family Lauraceae. It is a medium-sized evergreen tree native to China and Vietnam. It contains volatile oils composed of cinnamaldehyde, phenolic compounds, flavonoid derivates, methylhydroxychalcone polymer, mucilage, calcium oxalate, resins, sugars, and coumarins.
  • Cassia the species name for Cinnamomum aromaticum comes from the Greek work "kassia” meaning "to strip off the bark”. Cinnamon bark has been used medicinally in China since 2700 B. C. E and is said to supplement vital energy and blood, tone the kidney and spleen and acts as an antioxidant (Blumenthal et al. 1998).
  • Cinnamomum aromaticum has also been used in Korea, China and Russia as a traditional folk herb with hypoglycemic properties for the treatment of diabetes mellitus (Kim et al. 2005).
  • diabetes and cardiovascular disease The increasing prevalence of diabetes and cardiovascular disease is evident worldwide with an estimated 1700 new cases diagnosed daily (Jarvill-Taylor et al. 2001).
  • several million people worldwide are suffering from 'pre-diabetes' caused by high glucose levels with a resistance to insulin (Khan et al. 2003).
  • the primary function of insulin is to maintain low blood glucose, lipid and cholesterol levels to maintain a sense of well-being.
  • Cinnamomum aromaticum has been used as a hypoglycemic agent in ancient medicines (Kim et al. 2005). The modern therapeutic properties of cinnamon are supportable based on thousands of years of use in well established systems of traditional medicines, as well as some modern clinical studies (Blumenthal et al. 1998). A number of well proven in vivo animal studies on Cinnamomum aromaticum demonstrate that activation of the insulin receptor increases autophosphorylation resulting in an increase in glucose uptake and glycogen synthesis. However, there is a limited amount of published data on the effects of cinnamon consumption on blood glucose in humans. In vivo, in vitro and human studies have established that cinnamon extract regulates insulin activity and reduces serum glucose and cholesterol levels (Khan et al. 2003 and Kim et al. 2005).
  • Cinnamon capsules contained 1, 3 or 6 g of Cinnamomum aromaticum. After 20 days, only the 6 g cinnamon group showed significantly lower glucose levels. However, after 40 days, serum glucose (18-29%), triglycerides (23-30%) and total cholesterol (12-26%) concentrations were significantly lower in all cinnamon groups. Total cholesterol was lower in all groups at 40 days but low-density lipoprotein (LDL) concentrations were only significantly lower in the 3 g and 6 g cinnamon groups (10% and 24%, respectively).
  • LDL low-density lipoprotein
  • Vanschoonbeek et al. 2006 performed a 6 week standardized placebo-controlled study to investigate the proposed benefits of Cinnamomum cassia on 25 postmenopausal women diagnosed with type 2 diabetes. Patients were divided into two groups and supplemented with 1.5 g/day of Cinnamomum or placebo to assess the effects on glucose tolerance and whole-body insulin sensitivity. At 0, 2 and 6 weeks oral glucose tolerance tests and blood lipid profiles were performed resulting in no time x treatment interaction observed for fasting glucose, insulin concentration, insulin resistance, (oral glucose) insulin sensitivity or fasting blood lipid concentrations. This study shows cinnamon supplementation does not have a health benefit in patients with type 2 diabetes contradicting the results found by Khan et al. 2003.
  • Wister rats Wister rats. Qin et al. 2003 randomly assigned 18 rats into three groups: saline, 30mg/kg and 300mg/kg cinnamon extract. Cinnamon treatment for 3 weeks did not have an effect on plasma free fatty acids and fasting blood glucose concentrations. Although these levels were not affected in the cinnamon treated group, a difference was prevalent in glucose uptake compared to the placebo group. A dose-dependent manner was noticed with glucose utilization as 300mg/kg enhanced glucose utilization to a greater degree than the 30mg/kg or control groups.
  • Methylhydroxychalcone polymer MHCP
  • MHCP Methylhydroxychalcone polymer
  • 3T3-L1 adipocytes were assessed with MHCP to determine its function as an insulin mimetic.
  • the insulin treated adipocytes showed a 2.5 fold increase in glucose transport while the MHCP treated group did not show any increase.
  • glucose uptake increased in the MHCP treated group and at 60 minutes, a significant increase was noted.
  • the effect of cinnamon did not diminish immediately after stopping treatment.
  • the kinase receptor is activated resulting in phosphorylation of the insulin receptor, a similar effect is seen throughout the insulin signaling pathway.
  • Cinnamon soluble polyvinylpyrrolidone
  • PVP polyvinylpyrrolidone
  • Cinnamon extract mimics the same mechanism as insulin in adipocytes, increasing insulin sensitivity and glucose metabolism.
  • Cinnamomum aromaticum has convincingly been shown to prevent and control elevated glucose and blood lipid concentrations in both in vitro and in vivo studies and can be maintained for a long period after use.
  • the insulin kinase receptor is activated with cinnamon extract demonstrating insulin-mimetic activity. Elevated glucose and blood lipid concentrations increase the incidence of diabetes and/or cardiovascular health. The use of cinnamon extract can prevent these diseases by regulating the insulin receptor to increase glucose uptake and metabolism.
  • Cinnamomum aromaticum extract
  • Cinnamomum aromaticum acts as an insulin-mimetic by activating the kinase receptor and increasing insulin sensitivity.
  • the interaction within the intracellular kinase domain triggers an insulin-like response and stimulates glucose oxidation.
  • Cinnamon also regulates enzymes inside the insulin receptor kinase domain and inhibits both phosphotyrosine-specific protein phosphatase (PTP-I) in vitro and glycogen synthase kinase-3 ⁇ (GSK-3 ⁇ ) in vivo.
  • PTP-I phosphotyrosine-specific protein phosphatase
  • GSK-3 ⁇ glycogen synthase kinase-3 ⁇
  • Cinnamon acts independently from insulin but similar levels of activity were observed proposing that it may activate the same cascade as the insulin signaling pathways (Jarvill-Taylor et al. 2001).
  • Both test tube and animal studies have shown that compounds in cinnamon not only stimulate insulin receptors, but also inhibit an enzyme that inactivates them, thus significantly increasing cells' ability to use glucose.
  • Studies to confirm cinnamon's beneficial actions in humans are currently underway with the most recent report coming from researchers from the US Agricultural Research Service, who have shown that less than half a teaspoon per day of cinnamon reduces blood sugar levels in persons with type 2 diabetes.
  • the placebo-controlled study evaluated 60 people with type 2 diabetes (30 men and 30 women ranging in age from 44 to 58 years) who were divided into 6 groups. Groups 1, 2, and 3 were given 1, 3, or 6 grams of cinnamon daily, while groups 4, 5, and 6 received 1, 3 or 6 grams of placebo. After 40 days, all three levels of cinnamon reduced blood sugar levels by 18-29%, triglycerides 23-30%, LDL cholesterol 7-27%, and total cholesterol 12-26%, while no significant changes were seen in those groups receiving placebo. The researchers' conclusion: including cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases. (January 28, 2004)
  • cinnamon can prevent insulin resistance even in animals fed a high-fructose diet ⁇
  • a study published in the February 2004 issue of Hormone Metabolism Research showed that when rats fed a high- fructose diet were also given cinnamon extract, their ability to respond to and utilize glucose (blood sugar) was improved so much that it was the same as that of rats on a normal (control) diet.
  • Cinnamon is so powerful an antioxidant that, when compared to six other antioxidant spices (anise, ginger, licorice, mint, nutmeg and vanilla) and the chemical food preservatives (BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene), and propyl gallate), cinnamon prevented oxidation more effectively than all the other spices (except mint) and the chemical antioxidants. (March 6, 2004).
  • cinnamon is an excellent source of the trace mineral manganese and a very good source of dietary fiber, iron and calcium.
  • the combination of calcium and fiber in cinnamon is important and can be helpful for the prevention of several different conditions. Both calcium and fiber can bind to bile salts and help remove them from the body. By removing bile, fiber helps to prevent the damage that certain bile salts can cause to colon cells, thereby reducing the risk of colon cancer.
  • the body when bile is removed by fiber, the body must break down cholesterol in order to make new bile. This process can help to lower high cholesterol levels, which can be helpful in preventing atherosclerosis and heart disease.
  • Cinnamaldehyde also called cinnamic aldehyde
  • Cinnamaldehyde has been well-researched for its effects on blood platelets. Platelets are constituents of blood that are meant to clump together under emergency circumstances (like physical injury) as a way to stop bleeding, but under normal circumstances, they can make blood flow inadequate if they clump together too much.
  • the cinnaldehyde in cinnamon helps prevent unwanted clumping of blood platelets.
  • Cinnamon's essential oils also qualify it as an "anti-microbial" food, and cinnamon has been studied for its ability to help stop the growth of bacteria as well as fungi, including the commonly problematic yeast Candida. In laboratory tests, growth of yeasts that were resistant to the commonly used anti-fungal medication fluconazole was often (though not always) stopped by cinnamon extracts.
  • Cinnamon's antimicrobial properties are so effective that recent research demonstrates this spice can be used as an alternative to traditional food preservatives.
  • the broth was refrigerated without the addition of cinnamon oil, the pathogenic B. cereus flourished despite the cold temperature.
  • researchers noted that the addition of cinnamon not only acted as an effective preservative but improved the flavor of the broth.(October 1, 2003)
  • cinnamon has also been valued in energy-based medical systems, such as Traditional Chinese Medicine, for its warming qualities. In these traditions, cinnamon has been used to provide relief when faced with the onset of a cold or flu, especially when mixed in a tea with some fresh ginger.
  • Bitter melon is of the family Cucurbitaceae, genus Momordica and species charantia. Some synonyms include Momordica chinensis, M. elegans, M. indica, M. operculata, M.
  • sinensis, Sicyos fauriei, and its common names are bitter melon, papailla, melao de sao caetano, bittergourd, balsam apple, balsam pear, karela, k'u kua kurela, kor-kuey, ku gua, pava- aki, salsamino, sorci, sorossi, sorossie, sorossies, pare, peria laut, peria. It may be used as a whole plant, fruit or seed.
  • bitter melon is used for tumors, wounds, rheumatism, malaria, vaginal discharge, inflammation, menstrual problems, diabetes, colic, fevers, worms. It is also used to induce abortions and as an aphrodisiac. It is prepared into a topical remedy for the skin to treat vaginitis, hemorrhoids, scabies, itchy rashes, eczema, leprosy and other skin problems. In Mexico, the entire plant is used for diabetes and dysentery; the root is a reputed aphrodisiac. In Peruvian herbal medicine, the leaf or aerial parts of the plant are used to treat measles, malaria, and all types of inflammation.
  • bitter melon contains an array of biologically active plant chemicals including triterpenes, proteins, and steroids.
  • One chemical has clinically demonstrated the ability to inhibit the enzyme guanylate cyclase that is thought to be linked to the cause of psoriasis and also necessary for the growth of leukemia and cancer cells.
  • a protein found in bitter melon, momordin has clinically demonstrated anticancerous activity against Hodgkin's lymphoma in animals.
  • MAP-30 alpha- and beta-momorcharin and cucurbitacin B
  • MAP-30 A chemical analog of these bitter melon proteins has been developed and named "MAP-30"; its developers reported that it was able to inhibit prostate tumor growth.
  • HIV-infected cells treated with alpha- and beta-momorcharin showed a nearly complete loss of viral antigen while healthy cells were largely unaffected.
  • MAP-30 has been claimed to be "useful for treating tumors and HIV infections . . . " Another clinical study showed that MAP-30's antiviral activity was also relative to the herpes virus in vitro.
  • hypoglycemic blood sugar lowering
  • charantins steroidal saponins
  • insulin-like peptides insulin-like peptides
  • alkaloids steroidal saponins
  • bitter melon fruit and/or seed has been shown to reduce total cholesterol.
  • elevated cholesterol and triglyceride levels in diabetic rats were returned to normal after 10 weeks of treatment.
  • leaf of bitter melon have demonstrated broad- spectrum antimicrobial activity.
  • Various extracts of the leaves have demonstrated in vitro antibacterial activities against E. coli, Staphylococcus, Pseudomonas, Salmonella, Streptobacillus, and Streptococcus; an extract of the entire plant was shown to have antiprotozoal activity against Entamoeba histolytica.
  • the fruit and fruit juice have demonstrated the same type of antibacterial properties and, in another study, a fruit extract demonstrated activity against the stomach ulcer-causing bacteria Helicobacter pylori.
  • bitter melon capsules and tinctures are becoming more widely available in the United States and are employed by natural health practitioners for diabetes, viruses, colds and flu, cancer and tumors, high cholesterol, and psoriasis. Concentrated fruit and seed extracts can be found in capsules and tablets, as well as whole herb/vine powders and extracts in capsules and tinctures.
  • a study by Akhtar et al. in 1981 investigated the effect of dried and powdered M. charantia fruit on blood glucose level following oral administration to normal and alloxan- diabetic rabbits. Both normal and diabetic rabbits were randomly divided into 5 groups of six animals where group I served as a control whereas group II, III, IV and V were treated orally with 0.25, 0.5, 1.00 and 1.5 g/kg body weight of M. charantia powder suspended in 1% carboxymethyl cellulose solution in water respectively. Blood was collected from an ear vein immediately after M. charantia administration at 5, 10 and 24 hour time intervals.
  • the hypoglycemic effect was evident at 60 minutes after oral glucose and 60 and 120 minutes after i.p. glucose at a dose of 1 g/mL.
  • oral administration of aqueous extract of M charantia and residue after alkaline chloroform extraction reduced plasma glucose concentration within 1 hour also at a dose of lg/mL.
  • Material recovered by acid water wash of the chloroform extract at a dose of 0.002g/mL produced a slowly generated hypoglycemic effect.
  • Orally administered M. charantia extracts lower glucose concentrations independently of intestinal glucose absorption and involves an extra-pancreatic action.
  • the duration of the experiment was 30 days and then the rats were sacrificed.
  • the increase levels of blood glucose and decrease level of insulin in diabetic rats were normalized in M. charantia seed extract and glibenclamide treated diabetic rats.
  • the levels of thiobarbituric acid-reactive substances, lipid-hydroperoxides and reduced glutathione in both plasma and pancreas were significantly reversed to near normalcy after treatment.
  • the levels of vitamin C and vitamin E in plasma and the activities of superoxide dismutase, catalase and glutathione peroxidase in pancreas were reversed to near normal levels and decreased activities respectively after M. charantia seed extract and glibenclamide treatment.
  • controlling blood glucose level will thereby prevent the formation of free radicals or it may scavenge the reactive oxygen metabolites through various antioxidant compounds.
  • Vikrant et al. carried out an experiment to study the effects of different doses of alcoholic and aqueous extracts of M. charantia on the metabolic parameters of fructose fed rats. Fructose feeding led to insulin resistance-hyperinsulinemia, hyperglycemia and slight elevation in serum triglycerides levels in which only aqueous extracts at the dose of 400 mg/day significantly prevented development of hyperglycemic as well as hyperinsulinemia. Consequently, M. charantia might prove useful in the treatment and/or prevention of insulin resistance in non-diabetic state.
  • M. charantia in comparison to metformin which caused a 40 - 50% reduction.
  • the hypoglycemic activity of M. charantia is confirmed in both normal and diabetic animals as reported in the literature with similar responses from oral hypoglycemic drugs such as tolbutamide and metformin.
  • M. charantia was investigated in an animal model with type 2 diabetes with hyperinsulinemia. After 3 weeks of oral administration of the water extract of M. charantia, the blood glucose and serum insulin levels were lowered. The results were supportive of the traditional medical use of M. charantia as an antidiabetic agent in type 2 diabetes.
  • charantia are mostly concentrated on its antidiabetic activity despite the possibility that it might affect lipid metabolism due to the interconnection between carbohydrate and lipid metabolism (Senanayake et al. 2004 (a)). People with diabetes mellitus are at a higher risk of developing heart disease and other blood vessel diseases as such there have been studies reporting hypertriglyceridaemia and hypercholesterolemia in diabetic subjects (Chaturvedi 2005). There are a few experimental studies reported in literature that have examined the effect of M. charantia on triglyceride and cholesterol levels in normal and chemically induced diabetic animals.
  • bitter melon contains components which influence the metabolism of serum and liver lipids such that it may improve and/or ameliorate lipid disorders such as hyperlipidemia and fatty liver.
  • Ahmed et al. performed a study to investigate the long term effect of MC fruit extract on blood plasma and tissue lipid profiles in normal and streptozotocin (STZ)- induced type 1 diabetic rats.
  • Male Wistar rats were induced diabetic with a single intraperitoneal injection of a buffered solution of STZ at a dosage of 60 mg/kg body weight.
  • the animals were divided into four groups of six: diabetic, diabetic treated with karela extract, karela treated control and untreated control group.
  • karela juice exhibited an inhibitory effect on membrane lipid peroxidation in a dose-dependant manner due to some antioxidant components present in the fruit extract.
  • This study shows that besides its known hypoglycemic properties, karela fruit extract also exhibits strong hypolipidemic action on diabetic hypertriglyceridemia and hypercholesterolemia. Additionally, it has some antioxidative properties which contribute towards preventing lipid peroxidative damage.
  • the liver triglyceride levels in rats fed diets containing the methanol fraction at 1 % level was similar to those fed unfractionated Koimidori at 3%. Therefore, the potent active component of bitter melon lowering liver triglyceride concentrations is found to be concentrated in the methanol fraction.
  • the methanol fraction was able to lower liver cholesterol concentration in a dose-dependent manner.
  • bitter melon is useful in relieving and/or ameliorating life style-related diseases such as fatty liver, hypertriglyceridemia and diabetes.
  • the mechanisms proposed for effects on glucose and insulin include an inhibitory effect on glucose absorption in the intestine by decreasing hepatic gluconeogenesis, increasing hepatic glycogen synthesis and increasing peripheral glucose oxidation (Shibib et al. 1993 and Basch et al. 2003), enhanced insulin release from beta cells (Sitasawad et al. 2000 and Saxena and Vikram 2004) and an extrapancreatic effect via increased glucose uptake by tissues and increased GLUT4 transporter protein of muscles (Day et al. 1990, Sarkar et al. 1996 and Miura et al. 2001).
  • peripheral depots (Ahmed et al. 2001).
  • Thee new therapeutic formulation has also been proven as a powerful antioxidant and effective in helping to prevent cancer, heart disease, and stroke.
  • Another major benefit of the new therapeutic formulation is that it can prevent insulin resistance, a major and common complication that develops in people with type II diabetes in later years.
  • the two main ingredients of the new therapeutic formulation come from cinnamon and bitter melon, two natural products with long history both as foods and as medicines. Both the ingredients have been successfully used as effective remedies for many medical conditions in Indian, Chinese and South American Traditional Medicine.
  • the mechanism of actions are different from one another as cinnamon activates the insulin kinase receptor to increase insulin sensitivity through insulin-mimetic activity while the mechanisms for bitter melon include increased insulin secretion, tissue glucose uptake, liver muscle glycogen synthesis, glucose oxidation and decreased hepatic gluconeogenesis. As a result, combining these two ingredients has a synergistic effect which would lead to greater benefits for people with diabetes.
  • cinnamon and bitter melon has the potential to treat and prevent diabetes and other related cardiovascular diseases by lowering blood glucose levels and normalizing lipid profiles. Therefore, the combination of the medicinal ingredients is both novel and innovative.
  • the ratio of cinnamon to bitter melon may be varied and it is preferred that it be between sixty to seventy percent (60 - 70%) of cinnamon and forty to thirty percent (40 - 30%) of bitter melon.
  • One new therapeutic formulation contains cinnamon and bitter melon at a ratio of
  • the new therapeutic formulation also contains the highest concentration of water soluble flavonoids extracted from cinnamon (the part of the cinnamon extract responsible for its blood sugar lowering effect) compared to any other similar products in the market.
  • the dosage of bitter melon should in the range of 100 to 200 milligrams two to three times a day with at least one gram of cinnamon per day.
  • a particularly useful preparation is a 500 milligram capsule containing about 200 milligrams of bitter melon and 300 milligrams of cinnamon and one capsule should be taken twice a day to achieve the desired dosage.
  • One particularly useful formulation is as follows:
  • Cinnamon (Cinnamomi cassiae: Cinnamonum verum) 280 mg
  • the whole melon was used in a ration of 10:1 to produce the desired amount of bitter melon.
  • the diluent it was found useful to use microcrystalline cellulose in the amount of 150 milligrams mixed with one (1) milligram of dicalcium phosphate dihydrate. Magnesium stearate was used as the lubricant. The ingredients were mixed and placed in a gelatin capsule. Administration was also found to lower blood sugar levels and to normalize lipid profiles. [00099] The inventors have also found that a timed release formulation is useful to reduce blood glucose levels. Tests have shown that blood glucose levels of a person in the morning are at a fasting level, that is, about 4 to 5 mmol/L.
  • the blood glucose levels are under very tight control in the body. If they are too high, insulin is produced which drives excess blood glucose into the cells. If the levels are too low, glycogen is produced to raise the blood glucose levels. In Type 2 diabetes, there is little or no insulin available or its receptors are missing from the cells or it is substandard. Whatever the case, it is not available to push the excess glucose into the cells so that the blood glucose levels rise and diabetics must get exogenous insulin to stop this from happening.
  • a timed release preparation may be preferred and assists in returning blood glucose levels over a significant period of time.
  • a compressed tablet which will release the cinammon/bitter melon over the desired period of time.
  • CT compressed tablet
  • the release of the medication would take place over a twelve hour period.
  • a further CT taken in the evening would release the medication throughout the night thereby providing a level amount of blood glucose levels.
  • the inventors have found that a tablet comprising 500 mg of the cinnamon/bitter melon combination, from about
  • a lubricant, glidant and antiadherent 0.5% to about 3% of a lubricant, glidant and antiadherent; about 30% to about 50% of a compression agent and from about 0.5% to about 25% of a modified release agent will achieve the desired result.
  • Suitable lubricants, glidants and antiadherents include calcium, stearate, magnesium stearate, zinc stearate, stearic acid, talc, collidal silicas, sodium, benzoate polyethylene glycol, microscopic fumed silicas, micro-sized silicas.
  • Suitable compression agents may be selected from lactose, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, mannitol, sorbitol, microcrystalline cellulose, starch, corn-syrup solids, dextrose monohydrous, dextrose anhydrous, dextrose corn syrup, sucrose, fructose.
  • Appropriate modified release agents may include corn starch, modified starches, cellulose, alginic acid, sodium alginate, amonium calcium alginate, hydroxypropyl methylcellulose, sodium starch glycolate, sodium carboxymethylcellulose, colloidal silicates, ion exchange resin, wax, polyvinylpolyprrolidone, polyvinylpropalene.
  • the table is prepared using conventional compression techniques.
  • Kumar Shetty, A., et al. “Bitter gourd ⁇ Momordica charantia) modulates activities of intestinal and renal disaccharidases in streptozotocin-induced diabetic rats.” MoI. Nutr. Food Res. 2005; 49(8): 791-6.
  • Ahmed, L, et al. "Effects of Momordica charantia fruit juice on islet morphology in the pancreas ofthe streptozotocin-diabetic rat.” Z)z ⁇ ete5 /?e-f. Clin. Pract. 1998; 40(3): 145-51.
  • Sarkar, S., et al. "Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. " Pharmacol. Res. 1996; 33(1): 1—4.
  • Ahmed, L, et al. "Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (Karela) fruit extract in streptozotocin-induced diabetic rats.” Diabetes Res. Clin. Pract. 2001; 51(3):155 61.
  • IFN-gamma interferon-gamma
  • ThI T helper 1
  • Cucurbitane-type triterpenoids from the fruit of Momordica charantia Cucurbitane-type triterpenoids from the fruit of Momordica charantia.
  • Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats.
  • Microsomal triglyceride transfer protein gene expression and ApoB secretion are inhibited by bitter melon in HepG2 cells.
  • PAF Platelet-activating factor
  • Oxidative stress is the master operator of drug and chemically-induced programmed and unprogrammed cell death: Implications of natural antioxidants in vivo.
  • NIDDM diabetes mellitus
  • Amino acids conserved at the C-terminal half of the ribonuclease T2 family contribute to protein stability of the enzymes.
  • Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats.
  • PMID: 15139192 [PubMed - indexed for MEDLINE] Senanayake GV, Maruyama M, Shibuya K, Sakono M, Fukuda N, Morishita T, Yukizaki C. Kawano M, Ohta H. effects of bitter melon (Momordica charantia) on serum and liver triglyceride levels in rats, hnopha ⁇ nacol. 2004 Apr;91(2-3):257-62.
  • [D: 15120448 [PubMed - indexed for MEDLINE] Ichikawa M. Ohta M, Kanai S. Yoshida Y, Takano S. Ueoka T, Takahashi T. Kimoto K, Funakoshi A, Miyasaka K.
  • Momordica charantia extracts inhibit uptake of monosaccharide and amino acid across rat everted gut sacs in- vitro.
  • Natural dietary agents can protect against DMBA genotoxicity in lymphocytes as revealed by single cell gel electrophoresis assay. Teratog Carcinog Mutagen. 2003;Suppl 1 :71-8. PMID: 12616598 [PubMed - indexed for MEDLINE]
  • Alpha-glucosidase inhibitor from the seeds of balsam pear (Momordica charantia) and the fruit bodies of Grifola frondosa.
  • Dietary conjugated linolenic acid inhibits azoxymethane-induced colonic aberrant crypt foci in rats.
  • Medicinal foodstuffs XXI. Structures of new cucurbitane-type triterpene glycosides, goyaglycosides-a, -b, -c, -d, -e, -f, -g, and -h, and new oleanane-type triterpene saponins, goyasaponins I, II, and III, from the fresh fruit of Japanese Momordica charantia L. Chem Pharm Bull (Tokyo). 2001 Jan;49(l):54-63. PMID: 11201226 [PubMed - indexed for MEDLINE]
  • the antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1. Fertil Steril. 1999 Oct;72(4):686-90. PMID: 10521111 [PubMed - indexed for MEDLINE]
  • Alpha-momorcharin inhibits HIV-I replication in acutely but not chronically infected T- lymphocytes.
  • Ribosome inactivating protein and lectin from bitter melon (Momordica charantia) seeds sequence comparison with related proteins.
  • Patil SR Patil SR, Ravindra. Patil RS.
  • Singh A Singh SP. Bamezai R.
  • Momordica charantia (Bitter Gourd) peel, pulp, seed and whole fruit extract inhibits mouse skin papillomagenesis.
  • Singh A Singh SP. Bamezai R.
  • Plant foods in the management of diabetes mellitus vegetables as potential hypoglycaemic agents.
  • Antimicrobial activity of some medicinal plants extracts on Escherichia coli, Salmonella paratyphi and Shigella dysenteriae.
  • HIV human immunodeficiency virus
  • Ng TB Liu WK, Sze SF, Yeung HW.
  • alpha-momorcharin a ribosome inactivating protein
  • MAP 30 a new inhibitor of HIV-I infection and replication.
  • Trichosanthin, alpha-momorcharin and beta-momorcharin identity of abortifacient and ribosome-inactivating proteins.
  • Ng TB Ng TB, Wong CM. Li WW, Yeung HW.
  • Acid-ethanol extractable compounds from fruits and seeds of the bitter gourd Momordica charantia effects on lipid metabolism in isolated rat adipocytes.
  • Ng TB Ng TB, Wong CM. Li WW, Yeung HW.
  • Ng TB Ng TB, Wong CM. Li WW, Yeung HW.
  • Ng TB Ng TB, Wong CM, Li WW, Yeung HW.
  • Insulin-like molecules in Momordica charantia seeds Insulin-like molecules in Momordica charantia seeds.
  • balsam pear the fruit of Momordica charantia L.
  • PMID 3851122 [PubMed - indexed for MEDLINE]
  • the insulin-releasing activity of the tropical plant momordica charantia is the insulin-releasing activity of the tropical plant momordica charantia.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mycology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un produit à base de plantes comprenant de la cannelle (Cinnamomi cassiae : Cinnamonum verum) et de la margose (Momordica charantia). La cannelle et la margose sont toutes deux connues pour leur utilisation dans le traitement du diabète de type 2. L'association de la cannelle et de la margose démontre une synergie significative et un meilleur bénéfice thérapeutique chez les patients diabétiques.
PCT/CA2007/001066 2006-06-27 2007-06-15 Produit à base de plantes comprenant de la cannelle et de la margose pour traiter le diabète WO2008000063A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CA2,551,706 2006-06-27
CA002551706A CA2551706A1 (fr) 2006-06-27 2006-06-27 Produit a base d'herbes medicinales comprenant de la cannelle et du melon amer

Publications (1)

Publication Number Publication Date
WO2008000063A1 true WO2008000063A1 (fr) 2008-01-03

Family

ID=38834899

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2007/001066 WO2008000063A1 (fr) 2006-06-27 2007-06-15 Produit à base de plantes comprenant de la cannelle et de la margose pour traiter le diabète

Country Status (2)

Country Link
CA (1) CA2551706A1 (fr)
WO (1) WO2008000063A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012115723A1 (fr) 2011-02-25 2012-08-30 Medtronic, Inc. Passage en mode d'urgence pour les modes sans stimulation
WO2013103919A2 (fr) 2012-01-06 2013-07-11 Elcelyx Therapeutics, Inc. Compositions et procédés de traitement de troubles métaboliques
WO2013103384A1 (fr) 2012-01-06 2013-07-11 Elcelyx Therapeutics, Inc. Compositions à base de biguanide et procédés de traitement de troubles métaboliques
WO2014011926A1 (fr) 2012-07-11 2014-01-16 Elcelyx Therapeutics, Inc. Compositions comportant des statines, des biguanides et d'autres agents pour réduire un risque cardiométabolique
WO2014107617A1 (fr) 2013-01-05 2014-07-10 Elcelyx Therapeutics, Inc. Compositions et méthodes permettant de traiter des affections métaboliques
CN107412721A (zh) * 2017-09-15 2017-12-01 李玉保 一种降血糖苦瓜多肽复方胶囊及其制备方法
US9918489B2 (en) 2008-12-17 2018-03-20 Mark Gorris Food-based supplement delivery system
EP3763419A1 (fr) 2011-01-07 2021-01-13 Anji Pharma (US) LLC Traitements à base de ligand de récepteur chimiosensoriel
WO2022254233A1 (fr) * 2021-05-29 2022-12-08 Jasin Dahanayake Liyanage Jagath Manjula Nouvelle composition à base de plantes pour traitement de maladies non transmissibles comme le diabète et l'hypercholestérolémie dans le corps humain

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2567621A1 (fr) * 2006-11-10 2008-05-10 Innovative Life Sciences Corporation Produit a base d'herbes comprenant de la cannelle, du melon amer et des acides gras omega
FR2936952A1 (fr) * 2008-10-09 2010-04-16 Monique Bellec Administration par voie orale de medicaments et complements nutritionnels

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030185913A1 (en) * 2002-03-26 2003-10-02 Palpu Pushpangadan Herbal health protective and promotive nutraceutical formulation for diabetics and process for preparing the same
US20040142045A1 (en) * 2003-01-21 2004-07-22 Harris Dennis H. Therapeutic treatment for blood sugar regulation
US20050118324A1 (en) * 2003-12-02 2005-06-02 Mathew Anna M. Good living tea - a diabetic dietary supplement drink
WO2006127779A2 (fr) * 2005-05-26 2006-11-30 Suracell, Inc. Composition de supplement et son procede d'utilisation pour renforcer la sensibilite a l'insuline

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030185913A1 (en) * 2002-03-26 2003-10-02 Palpu Pushpangadan Herbal health protective and promotive nutraceutical formulation for diabetics and process for preparing the same
US20040142045A1 (en) * 2003-01-21 2004-07-22 Harris Dennis H. Therapeutic treatment for blood sugar regulation
US20050118324A1 (en) * 2003-12-02 2005-06-02 Mathew Anna M. Good living tea - a diabetic dietary supplement drink
WO2006127779A2 (fr) * 2005-05-26 2006-11-30 Suracell, Inc. Composition de supplement et son procede d'utilisation pour renforcer la sensibilite a l'insuline

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BLEVINS S.M. ET AL.: "Effect of Cinnamon on glucose and lipid levels in non-insulin dependent type 2 diabetes mellitus", DIABETES CARE *
KHAN A. ET AL.: "Cinnamon improves glucose and lipids of people with type 2 diabetes", DIABETES CARE, vol. 26, no. 12, 12 December 2003 (2003-12-12), pages 3215 - 3218 *
STEINMAN D.: "THE DOCTOR'S PRESCRIPTION FOR HEALTHY LIVING", vol. 9, December 2005, FREEDOM PRESS INC., article FOREMAN D.: "The glucose-balancing benefits of Cinnamon" *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9918489B2 (en) 2008-12-17 2018-03-20 Mark Gorris Food-based supplement delivery system
EP3763419A1 (fr) 2011-01-07 2021-01-13 Anji Pharma (US) LLC Traitements à base de ligand de récepteur chimiosensoriel
WO2012115723A1 (fr) 2011-02-25 2012-08-30 Medtronic, Inc. Passage en mode d'urgence pour les modes sans stimulation
WO2013103919A2 (fr) 2012-01-06 2013-07-11 Elcelyx Therapeutics, Inc. Compositions et procédés de traitement de troubles métaboliques
WO2013103384A1 (fr) 2012-01-06 2013-07-11 Elcelyx Therapeutics, Inc. Compositions à base de biguanide et procédés de traitement de troubles métaboliques
WO2014011926A1 (fr) 2012-07-11 2014-01-16 Elcelyx Therapeutics, Inc. Compositions comportant des statines, des biguanides et d'autres agents pour réduire un risque cardiométabolique
WO2014107617A1 (fr) 2013-01-05 2014-07-10 Elcelyx Therapeutics, Inc. Compositions et méthodes permettant de traiter des affections métaboliques
CN107412721A (zh) * 2017-09-15 2017-12-01 李玉保 一种降血糖苦瓜多肽复方胶囊及其制备方法
WO2022254233A1 (fr) * 2021-05-29 2022-12-08 Jasin Dahanayake Liyanage Jagath Manjula Nouvelle composition à base de plantes pour traitement de maladies non transmissibles comme le diabète et l'hypercholestérolémie dans le corps humain

Also Published As

Publication number Publication date
CA2551706A1 (fr) 2007-12-27

Similar Documents

Publication Publication Date Title
WO2008000063A1 (fr) Produit à base de plantes comprenant de la cannelle et de la margose pour traiter le diabète
Kumar et al. A medicinal potency of Momordica charantia
Mishra et al. Phytochemical, therapeutic, and ethnopharmacological overview for a traditionally important herb: Boerhavia diffusa Linn.
De Caluwé et al. Tamarindus indica L.–A review of traditional uses, phytochemistry and pharmacology
Subratty et al. Bitter melon: an exotic vegetable with medicinal values
Balogun et al. Gongronema latifolium: A phytochemical, nutritional and pharmacological review
Lucas et al. Health benefits of bitter melon (Momordica charantia)
Srinivasa et al. Fenugreek (Trigonella foenum-graecum L.) seed: promising source of nutraceutical
Ali et al. Dates (phoenix dactylifera) and date vinegar: Preventive role against various diseases and related in vivo mechanisms
Ahmad et al. Pharmacological activities of banana
Pal et al. Fenugreek (Trigonella foenum) seeds in health and nutrition
Kumar et al. Traditional use, phytochemistry and pharmacology of Ananas comosus (L.) Merr.(Family Bromeliaceae): An update
Dsouza et al. Extraction of Diosgenin from Fenugreek and evaluation of its pharmacological role in alleviating Metabolic Syndrome in vitro
WO2008055363A1 (fr) Produit à base d'herbes comprenant de la cannelle, du melon amer et des acides gras oméga-3
Jodh et al. Pharmacological review on Madhuca longifolia
Tshidzumba An inventory and pharmacological evaluation of medicinal plants used as anti-diabetes and anti-arthritis in Vhembe District Municipality, Limpopo Province
Padmavathi Chronic disease management with nutraceuticals
CA2560409A1 (fr) Produit a base de plantes renfermant de la cannelle et du melon amer
El-Sherif et al. Comparative Study for Group of Herbs VS. Glucophage Drug as Used for Obese Male Albino Rats
Upaganlawar Lagenaria siceraria (Bottle Gourd) in various cardiovascular complications
Akbar et al. Momordica charantia L.(Cucurbitaceae)
Hadi et al. Beneficial effects of gourds in health and diseases
Mohammed Junaidh et al. A review on walnut: Its pharmacological properties and role in human life
Manoharan et al. Anti-Diabetic evaluation of Hydro Alcoholic extract of Herbal Plant Oorithal Thaamarai Chooranam (Otc) on Streptozotocin (STZ) induced Type II Diabetes Mellitus in Wistar Albino Rats
Abd El-Ghany et al. Anti-diabetic effect of some herbs and fruit against streptozotocin induced diabetic rats

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07719982

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU

122 Ep: pct application non-entry in european phase

Ref document number: 07719982

Country of ref document: EP

Kind code of ref document: A1