WO2007006320A1

WO2007006320A1 - Drinkable oral insulin liquid and capsules

Info

Publication number: WO2007006320A1
Application number: PCT/EG2005/000022
Authority: WO
Inventors: Sherine Hassan Abbas Helmy
Original assignee: Sherine Hassan Abbas Helmy
Priority date: 2005-07-12
Filing date: 2005-07-12
Publication date: 2007-01-18

Abstract

The invention is a drinkable liquid and oral capsule of insulin. This invention is a new treatment for patients of Diabetes Mellitus. It is a sort of oral enterally delivered insulin in two dosage forms a drinking liquid form and soft gelatin capsule form. Normally peptide hormones like insulin are given by parenteral injection routes because they are destroyed by the acid and proteolytic enzymes in stomach and intestines and the absorbed traces are inactivated in the liver by the first pass metabolism. The orally administered form is the preferable and most convenient route for most patients that is why we concentrated our efforts searching this point. Some investigators did researches on alternative ways of drug delivery like the oral route but by buccal mucosal delivery or through inhalation but our invention is the first to give very highly bioavailable active insulin level by the ordinary oral drinkable enteral route.

Description

Drinkable Oral Insulin Liquid and Capsules

Technical field

Drinking oral insulin is a new method for treatment of diabetic patients (Type 1 and 2). Only 100 International Units of the formula on 1/2 cup of water, or as soft gelatin capsules are given to be drunk by the patient. The preparation was either oil or prepared micelles carrying the insulin.

The oil or the prepared micelles are absorbed directly from lacteals, differing from all other methods of insulin delivery as buccal, nasal, rectal beside the injection form. The early animal researches indicated the efficacy of this preparation on lowering blood glucose. Bioavailability studies did confirm the increased serum insulin levels following the administrated doses of the preparation in addition of decreasing in the levels of endogenous C-peptides, this added to the significant efficacy in lowering the blood glucose in series of 50 diabetic patients proved the importance of this invention as a potential successful treatment for diabetic patients.

Back ground Art

Normally peptide hormones like insulin are given as injection dosage forms because they are destroyed by the acid and proteolytic enzymes in stomach and intestines and the absorbed traces are inactivated in the liver by the first pass metabolism.

The orally administered form is the preferable and most convenient route for most patients that is why we concentrated our efforts searching this point.

Some investigators did researches on alternative ways of drug delivery like the oral route but by buccal mucosal delivery or through nasal or inhalation but our invention is the first to give very highly bioavailable active and safe insulin level by the ordinary oral drinkable route.

Disclosure of invention

This invention is a new treatment for patients of Diabetes Mellitus.

It is a sort of oral enterally delivered insulin in two dosage forms a drinking liquid form and soft gelatin capsule form.

Normally peptide hormones like insulin are given by parenteral injection routes because they are destroyed by the acid and proteolytic enzymes in stomach and intestines and the absorbed traces are inactivated in the liver by the first pass metabolism.

Some investigators did researches on alternative ways of drug delivery like the oral route but by buccal mucosal delivery or through inhalation but our invention is the first to give very highly bioavailable active insulin level by the ordinary oral drinkable enteral route. The processes of incorporating any form of aqueous or zinc insulin with any one or more from a list of several fatty acids starting from 4 carbon atoms butyric acid C-4 to arachidonic acid C-24 are involved in the invention claims, these fatty acids are required to synthesize either of aqueous miscelles and semi-oil insulin.

The dosage forms and all methods of preparation of the liquid and soft gelatin capsules of oral drinkable insulin are to be protected in our claims.

Several methods of preparation were involved as the following:- 1-To 6,00Ou of insulin add 5 ml of pyrogen free water and dissolving 1 gm of potassium bicarbonate to which 100 ml of polyethylene glycol 400 was added and 100 ml of a fatty acid from the list of protected fatty acids mentioned above like linolenic, linoleic, butyric oleic acid. This preparation was kept between 15 and 20 degree centigrade in order to prevent fatty acid from crystallization. This preparation is semi- oil preparation taken by the patient as 2 ml (100 u) to 1/2 cup of water and drinking or in soft gelatin capsule containing 50 units of insulin. 2-To 10,000 u of insulin add 100 ml of pyrogen free water 3 mg of NaHCO3 was added on 5-20 gm of Aspartame in water, stir until it become soluble. Add the prepared aspartame to dissolved insulin and complete it to 400ml by polyethylene glycole 400 and 10 ml of one, two or three of fatty acids from the list. This formula is kept at 10 to 15 degree centigrade and used as 5 ml on 1/2 cup of water and the patient drink it directly.

Animal studies on diabetic rat models demonstrated the blood glucose lowering effect of our invention.

Human phase 1 and 2 studies had been performed and showed the high bioavailability of our invention with elevated serum insulin and decreased C peptide levels.

While the efficacy studies revealed the marked glucose lowering effect.

Fifty patients had been investigated and showed significant glucose lowering effect reaching good controlling levels within 2 to 3 weeks with doses ranging from 50 to

100 international units before meals. The levels of fructosamine decreased from the range of 350 - 500 before treatment down to 200 - 280 ng/ml after 3 weeks of treatment.

Claims

1. The dosage forms and all methods of preparation of the liquid and soft gelatin capsules of oral drinkable insulin are to be protected.

2. The processes of incorporating any form of aqueous or zinc insulin with any one or more from a list of several fatty acids starting from 4 carbon atoms butyric acid C-4 to arachidonic acid C-24 are involved in the invention claims, these fatty acids are required to synthesize either of aqueous micelles and semi-oil insulin.

3. Several methods of preparation were involved as the following:-

1) To 6,00Ou of insulin add 5 ml of pyrogen free water and dissolving 1 gm of potassium bicarbonate to which 100 ml of polyethylene glycol 400 was added and 100 ml of a fatty acid from the list of protected fatty acids mentioned above like linolenic, linoleic, butyric oleic acid. This preparation was kept between 15 and 20 degree centigrade in order to prevent fatty acid from crystallization. This preparation is semi- oil preparation taken by the patient as 2 ml (100 u) to 1/2 cup of water and drinking or in soft gelatin capsule containing 50 units of insulin.

2) To 10,000 u of insulin add 100 ml of pyrogen free water 3 mg of NaHCO3 was added on 5-20 gm of Aspartame in water, stir until it become soluble. Add the prepared aspartame to dissolved insulin and complete it to 400ml by polyethylene glycole 400 and 10 ml of one, two or three of fatty acids from the list. This formula is kept at 10 to 15 degree centigrade and used as 5 ml on 1/2 cup of water and the patient drink it directly.