Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-10-26
2002-11-26
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C536S004100
Reexamination Certificate
active
06486127
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention provides methods to reduce serum lipids in insulin resistant subjects comprising administration of therapeutically effective amounts of D-chiro-inositol and lipid lowering medications. The present invention provides methods to treat a hyperlipidemic subject with insulin resistance comprising administration of D-chiro-inositol and a lipid lowering compound, either as concurrent single agents or as a combined composition. The methods and compositions of the present invention are particularly efficacious in treating insulin resistant subjects with a fasting blood glucose level of less than or equal to 180 mg/dL.
2. Related Art
Non-insulin dependent diabetes (NIDDM, or type 2 diabetes) is a worldwide health problem. According to the World Health Organization, an estimated 30 million people worldwide had diabetes in 1985. This number increased to 135 million people by 1995 and the WHO predicts a rise to 300 million people by 2025. The insidious nature of type 2 diabetes progression and medical complications that arise from hyperglycemia extract a heavy toll on the individual, healthcare resources, and society. As such, there is a continuing need for new therapeutic agents and therapeutic regimens that prevent diabetes, prevent or delay the progression of diabetes, or prevent or delay diabetic complications.
It is generally desirable to treat a subject with diabetes or at risk of developing diabetes in ways that reestablish or maintain the balance between insulin secretion and insulin sensitivity. It is highly desirable to employ methods that avoid administration of exogenous insulin. Therefore a regimen of diet and exercise is primarily used to attempt to establish more physiologic glycemic control. Sadly, however, pharmacological intervention becomes necessary. The current “second line” of therapies includes administration of pharmacological agents including sulfonylureas (e.g. GLUCOTROL®), biguanides (e.g. metformin), and PPAR gamma agonists (e.g. rosiglitazone) alone or in combination, which are used to increase endogenous insulin production, decrease hepatic glucose output, and increase periperial insulin sensitivity (Kobayashi,
Diabetes Obes. Melab
., 1(Suppl 1): S32-S40 (1999); Brown et al.,
J. Natl. Med. Assoc
., 91(7): 389-395 (1999)). Sulfonylureas are compounds that stimulate insulin secretion from beta cells in islet tissue of the pancreas and are currently the most frequently prescribed oral hypoglycemic drugs. Increased insulin secretion by sulfonylureas may lead to hypoglycemia (Imura,
N. Engl. J. Med
., 338: 908-909 (1998)). Unfortunately, prolonged use of sulfonylureas results in unfavorable side effects, particularly desensitization and/or apoptosis of the beta cells resulting in decreased insulin production. The effect is particularly manifest in subjects who have more severe insulin resistance in conjunction with less insulin production (Kobayashi,
Diabetes Obes. Metab
., 1(Suppl 1): S32-S40 (1999); Kolterman et al.,
Diabetes Care,
7(Suppl 1): 81-89 (1984)). Biguanides are compounds that decrease hepatic glucose output, and thus aid in controlling hyperglycemia. PPAR gamma agonists are insulin-sensitizing compounds that increase the cell's ability to respond to smaller quantities of insulin. Eventually these therapies fail and exogenous insulin is required to maintain a balance of glucose metabolism.
Many diabetic subjects are obese and exhibit elevated levels of free fatty acids and other serum lipids. Elevated free fatty acids and other serum lipids are associated with increased insulin resistance as well as other diabetic complications including hypertension, renal failure, and cardiovascular disease inter alia.
Currently there is intensive investigation into beneficial combinations of therapies that maximize the benefit to the diabetic subject, while minimizing the side effects of the individual therapeutic agents. Despite limited in vitro and in vivo models, it is currently difficult to predict the synergistic interaction in a human of any two drugs or classes of drugs a priori.
Lipid lowering medications, principally HMG-CoA inhibitors are a well known class of drugs that are commonly used to control serum levels of lipids. Although reasonably safe, these drugs have demonstrated a significant side effect, rhabdomyolysis, a condition that results in muscle cell breakdown and release of the contents of muscle cells into the bloodstream. One drug, cerivastatin, has been withdrawn from the market. Other statins demonstrate evidence of this same side-effect, though to much less severity. Therefore it would be desirable to maintain or increase the efficacy of these drugs while administering smaller quantities of the compounds to the subjects.
There is therefore, a need for new means to control lipid levels in diabetic subjects and thus prevent the progression of diabetes and prevent or delay the onset of diabetic complications. This need and others are provided in the present invention that describes methods of treating subjects suffering from insulin resistance comprising administration of a therapeutically effective amount of D-chiro-inositol (DCI) and a therapeutically effective amount of a lipid lowering drug.
SUMMARY OF THE INVENTION
The present invention provides a method of treating a subject in need thereof comprising: (a) administration of a pharmaceutically effective amount of a D-chiro-inositol-like compound; and (b) administration of a pharmaceutically effective amount of a lipid lowering drug, wherein the effective amounts of the D-chiro-inositol and the lipid lowering drug are administered in concurrent regimens.
The combination of D-chiro-inositol and lipid lowering drugs surprisingly results in greater serum lipid control than could be achieved with either DCI alone or lipid lowering drug alone. Thus the combination of D-chiro-inositol and lipid lowering drugs allows a pharmacological treatment that enhances lipid control, prevents progression of type 2 diabetes, and ameliorates diabetic complications related to elevated lipid levels. This beneficial effect is particularly effective in insulin resistant subjects having a fasting blood glucose of less than or equal to 180 mg/dl.
The present invention provides a method of treating dyslipidemic subjects with a combination of D-chiro-inositol, or a derivative or metabolite thereof, and a lipid lowering compound. The subject may be insulin resistant and/or clinically diagnosed with a medical condition such as impaired glucose tolerance, impaired fasting glucose, diabetes, polycystic ovarian syndrome, obesity, HIV-AIDS, cachexia or other such conditions.
The present invention also provides medicinal compositions comprising (a) a pharmaceutically effective amount of a D-chiro-inositol-like compound; (b) a pharmaceutically effective amount of a lipid lowering compound; and (c) a pharmaceutically acceptable carrier.
These compositions are useful in the methods of the present invention because they provide the convenience of a single dosage unit, and therefore increase patient compliance.
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Press Release, Richmond, Va, “Insmed Incorporated Announces Positive Results Of INS-1 In Patients With Type 2 Diabetes,” Jan. 4, 2001.
Allan Geoffrey
Gunn Ronald
Insmed Incorporated
Lewis Patrick
Stern, Kessler, Goldstein & Fox PLLC
Wilson James O.
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