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Title:  Method for treating, controlling, and preventing Diabetes Mellitus

United States Patent:   6,555,126

Issued:  April 29, 2003

Inventors:  Murad; Osama Mansour (Amman, JO); Seir; Husni Abu (Amman, JO); Farouqi; Hafez Taji (Amman, JO)

Assignee:  Diabex, Inc. (Wake Forest, NC)

Appl. No.:  753113

Filed:  January 2, 2001

Abstract

This invention pertains to a method that can control, treat, and prevent Diabetes Mellitus. The method includes means of administering a potent product, including mainly the active ingredient Linalool, in any one of several forms, alone or with other additives and catalysts, such as vitamin E to enable the body to handle and control, then correct the complications of Diabetes Mellitus. A modest percentage of users suffering from this disease can be cured completely while the majority of others improve remarkably and experience lower blood glucose and reduce the glycated hemoglobin HbAlc readings to what are medically acceptable and healthy levels. Others, who are vulnerable to the disease due to hereditary factors, or other reasons, can help prevent it. The method works in several ways, including activation of the pancreas and re-establishing the ability of body cells to utilize and handle better and well, the glucose in the blood, and regulate the level of natural insulin in the body. The method employs Linalool in any one of its forms that can be found naturally or synthetically.

OBJECTS OF THE INVENTION

It is among the objects of this invention to provide a method for treating and lowering the hyperglycemia of diabetic patients.

It is another object of this invention to lower the HbAlc readings to normal levels. To enable the body to deal and control the complications of Diabetes Mellitus.

To cure diabetic patients from this disease by lowering blood sugar to normal levels permanently.

To prevent the onslaught of Diabetes Mellitus in vulnerable patients, with family history of the disease.

DETAILS OF THE INVENTION

In arriving to the conclusive results, indicated, many experiments were conducted, including:

Animal Studies

Limited clinical studies

ANIMAL STUDIES

The following study was carried out and controlled by Pharmacy College, Jordan University.

1. LD 50: For this determination, 59 rats (Rattus rattus) of both sexes were used with body weights of 200-240 grams to determine the LD50. The rats were divided into groups consisting of 5-6 rats each.

The rats were fed standard laboratory pellet diet and water ad libitum. Linalool was given as one single dose subcutaneously to rats in gradually increasing doses of 0.2 ml/kg body weight, 0.25 ml/hgkg, 0.3 ml/kg, 0.35 ml/kg, 0.40 ml/kg, 0.45 ml/kg, 0.50 ml/kg, 0.55 ml/kg, 0.60 ml/kg, 0.65 ml/kg.

LD 50 was determined to be 0.63 ml/kg body weight.

2. Hypoglycemic studies of Linalool effect on Normal and Diabetic rats:

Preparation of Animals: For each experiment, eight (8) overnight fasted normoglycemic and diabetic rats were used. The animals were kept in the experimental animal laboratory for three days with free access to food and water.

Hyperglycemia was induced in the diabetic group of rats by a single intraperitoneal injection of Streptozocin (Upjohn Co, Kalamazoo, Mich., USA). 6 mg/kg body weight-freshly dissolved in citrate phosphate buffer with pH adjusted to 4.5.

Diabetes was confirmed one week after administration of Streptozocin by determining the fasting blood glucose concentration. Most of the rats exhibited blood glucose concentration in the range of 400-500 mg/dl. The fasting blood glucose concentration in normal rats is 90-120 mg/dl.

On the day of the experiment, blood samples were collected at zero time before IP injection of the test substance (Riedel De Hein--Germany), and at intervals as given in Table 1 and 2. Blood samples were drawn from the ear vein in 100 micro millimeter heparinized capillary tubes.

Blood glucose concentrations were determined according to glucose oxidase method, using glucose enzymatic kits (Biomerioux France).

The percentage change in glycaemia was calculated.

For control animals, sterile saline solution was used instead of Linalool.

STATISTICAL ANALYSIS

Data are expressed as means and standard error of the mean (S.E.M.) statistical analysis were performed using student's t test. The values were considered to be significantly different when P-value was less than 0.05.

Our results show that Linalool (Tables #1 and #2) has significant hypoglycemic activity in normoglycemic and hyperglycemic rats. For these normoglycemic rats, the highest activity was observed at four hours after the intraperitoneal injection of Linalool. For hyperglycemic rats the highest activity was observed at 24 hours after the Linalool injection.

 

                             TABLE 1
    Short term hypoglycemic effect of a single intraperitoneal injection
    of Linalool (0.2 ml/kg) on blood glucose concentration of normal and
                    Streptozocin diabetic rats
                                       Change in blood glucose
                      Pretreatment glu-            % at
                      cose (mg/100 ml)    15 min.        1 h.
    Normoglycemic
    rats:
    Saline                108 + 10.2   3.2 + 1.7   1.4 + 0.6
    Linalool            116.5 + 8.7 -36.1 + 7.7* -35.2 + 6.2*
    Hyperglycemic rats:
    Saline                519 + 58.8   2.1 + 0.5  -2.4 + 0.8
    Linalool            443.6 + 28.9 -32.1 + 3.6*   -35 + 3.4*
    *Significant to pretreatment values at P < 0.05
    Tabular values represent the mean S. E. M.


TABLE 2 Effect of a single intraperitoneal injection of Linalool (0.2 ml/kg) on blood concentration of normal Streptozocin diabetic rats within 24 hours Pretreatment glucose Change in blood glucose % at (mg/100 ml) 1 h. 4 h. 24 h. Normoglycemic rats: Saline 99.3 + 4.6 2.0 + 0.6 2.9 + 1 5.4 + 2.5 Linalool 122 + 2.2 -35.2 + 6.2* -40.9 + 8.2* -18.9 + 4.4* Hyperglycemic rats: Saline 437 + 22.4 5.3 + 1.1 4.02 + 2.3 -1.1 + 0.9 Linalool 478 + 31.9 -36.4 + 8.6* -43.7 + 6.6* -55.8 + 6.2* *Significant to pretreatment values at P < 0.05 Tabular values represent the mean S. E. M.



There was no remarkable difference in the hypoglycemic activity in the first hour between the normo and hyperglycemic rats. This hypoglycemic activity within the first four hours after the administration of Linalool, (33.2% and 36.4%) was compared to the hypoglycemic activity of a short acting soluble insulin preparation. When 5 units of insulin were injected IP the decrease in blood glucose concentration was after one hour by the normoglycemic rats 49% and by the hyper-glycemic rats 47.1%. As expected, the decrease in blood glucose concentration upon insulin injection was insignificant within the first 15 min (17.1%) while this decrease was 36.1% by normoglycemic and 32.1% by hyperglycemic rats treated by Linalool.

RESULTS

These observations indicate that Linalool has a rapid acting and long lasting hypoglycemic activity. (Table 1 and 2).

DETAILS OF THE INVENTION

The invention is a method of administering of Linalool, alone, or Linalool with vitamin E, to treat Diabetes Mellitus.

Linalool, whose empirical formulae is (3,7 dimethyl-1,6-octadien-3-ol) can be obtained naturally or synthetically while maintaining the same level of effectiveness towards treating and preventing Diabetes Mellitus.

Linalool is also recognized by the FDA as safe, and approved flavoring substance suitable for human consumption. The method consists of administering Linalool in many forms but preferably in enteric coated softgels containing a therapeutically effective amount of Linalool oil, and vitamin E, mixed together or separately.

Daily dosages of Linalool can range from 0.20 ml, to 3 ml/day, divided in three equal doses. Vitamin E, in all its forms, alpha tocopherols beta, gamma, and delta tocopherols can be used in the product. Vitamin E is an effective antioxidant element. It is a cell protector against per oxidation of the cells of the body including beta cells of the pancreas that help maintain good function of the body cells. The outcome of this process is maintaining good function of body cells.

Dosages of vitamin E range from 0.5 mg to 20 mg/kg body weight per day in three divided doses.

The method of the invention employs the use administering of the product in the following forms:

Injectable form.

Suspension--drops, tablets, capsules.

Suppositories

Local topical applications

Stabilizers and anti-oxidants can be added to the preparation.

In the preferred embodiment of the method of the invention, a therapeutically effective amount of Linalool alone or with vitamin E, is filled into softgel enteric coated capsules. The capsules are made by a process that involves filtration of the oil, then filling the oil into softgel capsules of the selected size, with or without adding preservatives, adding anti oxidants, and then coating the ingredients by employing a reliable enteric coating method. Then packaging into hygienic packs with protection against humidity. The packaging marked with the manufacturing and expiration dates.

In the preferred embodiment of the method of the invention, the softgel enteric coated capsules contain each:

Linalool 0.5 ml,

Vitamin E 100 mg

Dosage of the preferred embodiment is 1 to 3 capsules per day taken with meals.

Duration of treatment in the preferred embodiment is three to six months.

Limited Clinical Study

The study was conducted with strict and continuous monitoring of all vital physical parameters of all volunteers. No clinical or biochemical side effects were observed during or after the test periods. Special attention was made while monitoring Blood Urea, Serum Creatinine, SGPT, Cholesterol, and Triglycerides.

The study involved over 200 diabetic volunteers with different types of Diabetes Mellitus and from different countries, and of both sexes. The breakdown was as follows:

Group One: Two (2) volunteers were new Diabetes Mellitus patients (Virgin cases).

These volunteers had never been treated for the disease and never taken any of the known and standard Diabetes Mellitus medications.

Volunteer from (Group One)--Mr. A. M. Shanawani, Male, 45 years old, (Jordan citizen). First determined to be diabetic on Jan. 21st, 1999. Readings with no previous medications, or treatments were as follows:

        Feb. 2, 1999    Serum Glucose, Fasting   184 mg/dl
                        HbAlc                    9.0%
                        Insulin, Fasting         10 uU/mL
                        Serum Glucose PP         343 mg/dL
                        Insulin PP               37.20 uU/mL



Started using Linalool Enteric Coated Softgels 0.45 ml 3 times daily with meals, on Feb. 22nd, 1999.

        Apr. 13th, 1999 Serum Glucose, Fasting   120 mg/dL
                        HbAlc                    8.00%
                        Insulin, Fasting         10.70 uU/mL
                        Serum Glucose PP         257 mg/dL
                        Insulin PP               57.01 uU/mL
        May 25, 1999    Serum Glucose, Fasting   125 mg/dL
                        HbAlc                    6.70%
                        Insulin, Fasting         7.30 uU/mL
                        Serum Glucose PP         244 mg/dL
                        Insulin PP               59.10 uU/mL
        Jul. 18, 1999   Serum Glucose, Fasting   136 mg/dL
                        HbAlc                    6.40%
                        Insulin, Fasting         5.90 uU/mL
                        Serum Glucose PP         244 mg/dL
                        Insulin PP               72.80 uU/mL



Interpretation of Results

Above volunteer enjoyed drastic improvement in hyperglycemia, because of the Linalool method of treatment, due to activation of the beta cells, and therefore their ability to secrete insulin. Since no insulin injections were given to this volunteer, the increase in his insulin levels PP is attributed to the Linalool Treatment Method only. The results prove that this method of treatment enabled the pancreas to perform in a normal manner by increasing the output and production of insulin when needed at the PP stage.

Group Two: One (1) volunteer had hyper insulinemia with readings of 400 mg/dl of glucose

2--Volunteer Mr. Omar Bakir--Male, Age 55 years (Jordan citizen).

Diagnosed to be diabetic on Feb. 28th, 1997

Readings with no previous medications, or treatments were on Mar. 29, 1997 as follows:

        Feb. 2, 1999    Serum Glucose, Fasting   197 mg/dl
                        HbAlc                    8.2%
                        Insulin, Fasting         42 uU/mL
        May 17, 1999    Serum Glucose, Fasting   200 mg/dl
                        HbAlc                    8.1%
                        Insulin, Fasting         18.40 uU/mL
        June 24, 1999   Serum Glucose, Fasting   222 mg/dl
                        HbAlc                    7.5%
                        Insulin, Fasting         25.6 uU/mL



Interpretation of Results

Above volunteer had high level of fasting insulin, 42 uU/mL but was still suffering from diabetes, thus he had hyper insulinemia. His HbAlc reading was lowered to 7.5% while insulin level decreased to 25.6, almost a 50% reduction. This means that Linalool caused improvement in utilizing glucose, due to activation of insulin receptors in peripheral cells.

Comments on Group One and Two

From above two volunteers, it is established that the product of the method of the invention method has two actions:

Increased production and secretion of insulin by the pancreas.

Activation of the insulin receptors of the cells increasing the glucose utilization by the body.

Group Three

The study involved over two hundred diabetic volunteers of both sexes, who had the disease from 3 to 25 years. In various lots, the volunteers were on insulin alone, insulin and hypoglycemic drugs, or hypoglycemic drugs alone. The patients took the product in the form of softgel enteric coated capsules (0.5 ml Linalool and 100 mg vitamin E) one capsule with meals three times a day. The duration of treatment was minimum three months. The product was given along with the classical hypoglycemic treatment (insulin and others). These classical hypoglycemic medications, Insulin--morning and evening, and Daonil (Glibenclamide 5 mg), Glucaphage (metformin 850 mg and other medications, were decreased gradually depending on the monitored improvements of the patient condition.

Results of the Group Three Study

HbAlc was lowered to normal levels in all patients.

The fasting blood sugar was lowered to normal levels.

In three cases, complete cure was accomplished, with no further anti diabetic drugs taken.

Select examples of volunteers from Group Three: (Summary of readings):

             3 - Mr. L. W. 50 years, U.S.A. citizen.
        Blood test, Glucose Fasting Oct. 15, 1998 333 mg/dL
        Blood test, Glucose Fasting Nov. 9, 1998 285 mg/dL
        May 25                                  153
        June 1                                  153
        HbAlC Readings:
        Oct. 15, 1998                           HbAlc 9.0%
        Jan. 4, 1999                            HbAlc 8.1%
        Apr. 7, 1999                            HbAlc 6.9%



4--Mr. T. B., 68 years old, USA Citizen, semi retired from serving as a high ranking executive in the railroad industry and the State government. He has been treated regularly by the Linalool method, and enjoyed regular and continuous improvements in his condition.

He writes on Jul. 7th, 1999 "after reviewing my report last month, my physician reduced my medication to one half. He indicated that if my readings continued to be low, he would take me off all medication".

On July 14th, his physician decided to take him off all medication, and considered him CURED. Below, is history of his readings:

    Dec. 17         175 mg/dL
    Dec. 24         163
    Jun. 18         109
    Jun. 26         105
    Jul. 26, 1999   105 mg/dL
    HbAlc Readings: Were lowered from 9.3% to 6.18% 
    on Jun. 4, 1999.



5--Mr. Y. A., 52 years old, Jordan citizen, diabetic for over 20 years. His best HbAlc reading occurred on Jan. 27th, 1999 and was 7.0%, down from a high of 11.2% on Jul. 27th, 1998.

It is also worth noting that this volunteer, a leading financier and president of a well known Middle Eastern bank, who regularly undergoes general physical tests in the USA, has been treated with the method of the invention for over three years, in various embodiments of the method, including injections and orally. Despite his disregard for dietary caution, the volunteer continued to eat large amounts of sweets and fat rich foods, yet benefited tremendously, with no ill effects or negative signs in his general health. He confirms his belief that his health is continuously improving and attributes that to the Linalool method. He says, "As far as knowing my general health and diabetic condition are concerned, I am as good as any of my doctors."

READINGS

                             READINGS
                             Fasting Blood Sugar       HbAlc
          Jul. 27, 1998      233 mg/dL               11.2%
          Aug. 17, 1998      190                     10.1%
          Sep. 17, 1998      166                      9.7%
          Nov. 1, 1998       114
          Nov. 12, 1998      135                      7.5%
          Jan. 27, 1999      167                      7.0%

Claim 1 of 24 Claims

What is claimed is:

1. A method for treating hyperglycemia comprising administering a therapeutically effective amount of Linalool to a patient in need thereof.

 


____________________________________________
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