Oral insulin therapies and protocol
First Claim
1. A method of treating a diabetic patient, comprising:
- orally administering to an early stage type II diabetic patient, at a time from about 30 minutes prior to ingestion of a meal to concurrently with ingestion of a meal, a dose of a therapeutically effective amount of unmodified insulin with from about 20 to about 600 mg of a pharmaceutically acceptable delivery agent that facilitates absorption of said insulin from the gastrointestinal tract, said dose contained in one or more pharmaceutically acceptable tablets, to provide a time to maximum plasma concentration of insulin at a time point from about 15 to about 20 minutes after oral administration of said dose, said dose being sufficient to compensate for the lack of a first phase insulin response which occurs endogenously in a non-diabetic subject in response to an ingested meal.
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Accused Products
Abstract
Methods for treating impaired glucose tolerance and early and late stage diabetes in mammals, for prophylactically sparing β-cell function, aiding in preventing β-cell death, preventing the onset of overt diabetes in a mammal with type 2 diabetes, treating the current level of glycemic control dysfunction of a mammal with impaired glucose tolerance or diabetes, comprising orally administering insulin and a delivery agent that facilitates insulin absorption from the gastrointestinal tract at the time of or shortly before mealtime, e.g., within about 10 minutes prior to ingestion of a meal, on a chronic basis. The methods also comprise, in addition to administering a rapid-acting insulin to provide a first insulin peak, administering a slow acting insulin to provide a second insulin peak occurring at a later time but of a longer duration. These methods achieve improved glycemic control without the risks of hypoglycemia, hyperinsulinemia and weight gain and the need for frequent blood glucose monitoring that are normally associated with insulin therapy.
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Citations
87 Claims
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1. A method of treating a diabetic patient, comprising:
orally administering to an early stage type II diabetic patient, at a time from about 30 minutes prior to ingestion of a meal to concurrently with ingestion of a meal, a dose of a therapeutically effective amount of unmodified insulin with from about 20 to about 600 mg of a pharmaceutically acceptable delivery agent that facilitates absorption of said insulin from the gastrointestinal tract, said dose contained in one or more pharmaceutically acceptable tablets, to provide a time to maximum plasma concentration of insulin at a time point from about 15 to about 20 minutes after oral administration of said dose, said dose being sufficient to compensate for the lack of a first phase insulin response which occurs endogenously in a non-diabetic subject in response to an ingested meal. - View Dependent Claims (2, 80, 81, 82, 83)
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3. A method of treating a patient with type I diabetes or late stage type II diabetes, comprising:
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orally administering to said patient, at the time of or shortly prior to ingestion of a meal, a unit dose of from about 10 Units to about 600 Units (from about 0.4 mg to about 23 mg) of unmodified insulin with from about 20 to about 600 mg of a pharmaceutically acceptable delivery agent that facilitates absorption of said insulin from the gastrointestinal tract to provide a time to maximum plasma concentration of insulin at a time point from about 15 to about 20 minutes after oral administration of said dose, said dose being sufficient to compensate for the lack of a first phase insulin response which occurs endogenously in a non-diabetic subject in response to an ingested meal, and administering to said patient a separate dose of insulin in an effective amount to replace a second phase insulin response to a meal which occurs a non-diabetic subject substantially from endogenous insulin release. - View Dependent Claims (4, 5, 6, 7, 8, 9, 35, 36, 84, 85, 86, 87)
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10. A method of treating pre-diabetic patients, early stage type 2 patients and/or late stage type 2 diabetic patients comprising:
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orally administering to the mammal on a chronic basis a pharmaceutical formulation comprising a therapeutically effective dose of insulin and a delivery agent that facilitates absorption of insulin from the gastrointestinal tract, discontinuing said chronic administration, and obtaining, as a result of said chronic administration, an improved effect as compared to baseline levels before said chronic administration, said improved effect selected from the group consisting of improved glucose tolerance, improved glycemic control, improved glucose homeostasis, spared β
-cell function, prevention of β
-cell death or dysfunction, reduction in systemic hyperinsulinemia, delay in the onset of overt or insulin dependent diabetes, reduction in the incidence of a disease state associated with chronic dosing of insulin, improved insulin utilization and insulin sensitivity, and improved insulin secretion capacity. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 37, 38, 39, 40, 41, 42, 43, 44, 45)
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46. A method for treating a patient in accordance with the patient'"'"'s stage of development of diabetes mellitus, comprising:
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(a) identifying a patient'"'"'s stage of diabetes along a continuum of development of diabetes as one of prediabetic stage, early stage type 2 diabetes, late stage type 2 diabetes and type 1 diabetes; and
(b) recommending a treatment to said patient that includes an oral insulin treatment appropriate to said patient'"'"'s stage along the continuum of development of diabetes. - View Dependent Claims (47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)
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- 58. An oral solid dosage form comprising a dose of unmodified insulin and an effective amount of a delivery agent that facilitates the absorption of the insulin from the gastrointestinal tract and an excipient, one or more of said dosage forms upon administration to a diabetic patient at a time from about 30 minutes prior to ingestion of a meal to concurrently with ingestion of a meal providing a therapeutically effective reduction in blood glucose after oral administration and a time to maximum plasma concentration of insulin at a time point from about 15 to about 20 minutes after oral administration, said total dose being sufficient to replace an endogenous first phase insulin response to an ingested meal in a non-diabetic subject.
- 60. A substantially homogeneous oral tablet comprising a therapeutically effective dose of insulin, a delivery agent that facilitates absorption of insulin from the gastrointestinal tract and an excipient suitable for tableting, said tablet upon administration to a diabetic patient at a time from about 30 minutes prior to ingestion of a meal to concurrently with ingestion of a meal providing a therapeutically effective reduction in blood glucose after oral administration.
Specification