US 3911915 A
A method of nourishing warm blooded animals comprising the parenteral introduction of a maltose solution in a pharmaceutically acceptable carrier into the living body. The solution may constitute all or part of the total diet and may be supplemented by amino acids, vitamins, minerals and/or medication. The method may also be used as part of blood dialysis as, for example, in the case of kidney failure.
Description (OCR text may contain errors)
United States Patent Seifter et a1.
DIALYTIC INTRODUCTION OF MALTOSE INTO BLOODSTREAM Inventors: Eli Seifter, New Hyde Park;
Giuseppe Rettura, Bronx, both of N.Y.
Albert Einstein College of Medicine, New York, NY.
Filed: Sept. 5, 1972 App]. No.: 286,409
US. Cl 128/214 R; 128/213; 128/D1G. 3; 210/22; 424/180 Int. Cl. A61M 5/00; A61M l/O3 Field of Search 424/180; 128/214 R, 214.2, 128/213, DIG. 3; 23/2585; 210/22, 321
References Cited UNITED STATES PATENTS 5/1967 Dyke 424/180 GLUCOSE MALTOSE AVERAGE WEIGHT LOSS, lN HUNDRED GRAMS/DOG 1 Oct. 14, 1975 9/ 1969 Revici 424/ 1 80 8/1970 Roberts 210/22 Primary ExaminerDalton L. Truluck Attorney, Agent, or Firm-Bierman & Bierman 2 Claims, 1 Drawing Figure DAYS ON DIET US. Patent Oct. 14, 1975 3,911,915
GLUCOSE MALTOSE AVERAGE WEIGHT LOSS, 1N HUNDRED GRAMS/DOG Ullllllllllllllllllllllllllllllllllllllllllllllllllllll DAYS ON DIET DIALYTIC INTRODUCTION OF MALTOSE INTO BLOODSTREAM The invention described herein was made in the course of work under a grant or award from the Department of Health, Education, and Welfare.
The invention is concerned with an improved method of feeding warm blooded animals, more specifically with a substitute for a standard glucose presently used for that purpose.
While glucose solutions have been used to provide calories for patients who are unable, for one reason or another, to eat normally, they present certain problems and limitations. Diabetics or pre-diabetics do not tolerate glucose well and, in addition, even many normal paticnts may react unfavorably to the administration of this sugar. Some go into a reactive hypoglycemia.
Furthermore, by the use of the existing glucose administration it is not possible to provide much more than about 800 calories per day. This is far lower than is required to sustain the normal human being at an appropriate weight. Moreover, large volumes of water are required since the maximum concentration suitable is a 5% solution of glucose.
In the pre-existing practice glucose has been administered intravenously either into a peripheral vein or into a large vein. In the former case a maximum concentration of 5% can be used and about 4 liters per day are infused. If a stronger solution is used, the increased osmotic pressure may irritate the vessel walls and will induce problems of fluid balance in the patient. The use of such solutions will cause first a deep hyperglycemia which, in turn, causes a hyper secretion of insulin which, ultimately, results in hypoglycemia. If a greater than 4 liter volume per day is attempted this may cause difficulties in patients with cardiac or renal disease.
Glucose is sometimes administered as a hypertonic solution l0 20%) into a large vein such as the superior vena cava. In such case 3 liters of a 20% solution may be used daily. However, these solutions frequently provoke metabolic responses which are not always easy to control.
There is a definite need for a treatment that will provide from 1600 to 2400 calories per day and, at the same time, avoid the necessity of entering a large blood vessel. In addition, such improved treatment should minimize swings in blood glucose and should be capable of being given intermittently.
The present invention is intended to accomplish the foregoing objectives and consists in the substitution of maltose for the previously used glucose. It will be appreciated that one of the limiting factor in the use of glucose is the osmotic pressure generated by the solution. If the osmotic pressure exceeds that of the body cells, water from the interior of the cells will tend to pass through the cell walls by reverse osmosis. Thus, a serious problem can arise when the feeding is to take place over a long period of time.
It has been found that a maltose solution has an osmotic pressure which is approximately one-half that of a correspondingly concentrated solution of glucose. This permits the administration of a solution of maltose and enables the introduction into the body of at least twice the number of calories which can be given using the glucose solution.
The maltose solution can be introduced intravenousl y, intraperitoneally or subcutaneously. It can constitute all or part of the total diet of the patient. Additional nutrients can be included in the solution including amino acids, vitamins, minerals and the like. Moreover, medication may also be dissolved in the solution and administered to the patient along with the maltose.
It is quite surprising that maltose should be suitable for this purpose since two very common disaccharides (sucrose and lactose) are ineffective when given parenterally. This is true even though both of these sugars are, of course, fully utilizable and metabolizable when taken orally. It would be expected that maltose which is also a disaccharide similar to sucrose and lactose would also be ineffective when given parenterally.
In order to demonstrate the usefulness of maltose for the purposes described the following examples are included. They are intended to be illustrative only and do not constitute any limitation on the invention.
EXAMPLE 1 Male SpragueDawley rats weighing 275 gm each were the subjects of this experiement. These animals at the age tested had a slow growth rate. The rats were divided into four groups and all were housed individually in metabolic cages so that no portion of the diet was lost. These cages permit the collection of any food which the animals may spill so that it can be re-fed to the rats.
The animals were fed a diet of Rockland Chow and were also given maltose parenterally.
The animals in Group A received as much Chow as they desired. Food was always present in their cups and they were permitted to eat ad libitum.
The animals in Groups B, C and D each received 10 gm of Rockland Chow per day. This amount is less than 50% of that consumed by the animals in Group A. It contains an adequate amount of protein (2.1 gm per rat per day). It does not contain enough digestible carbohydrates to maintain body weight. The oral intake of the various groups is set forth in Table I.
TABLE 1 Protein Intake Calorie Intake Group (gm per rat per day) (per rat per day) A 5.3 B 2.1 40 C 2.1 40 D 2.1 40
be appreciated that for human beings the comparable concentrations would be 5% and 10%, respectively. These'solutions are, of course, not isocaloric.
The animals were weighed twice daily and were killed after five days of the experiment. No abnormalities were noted and, in particular, the liver weights were all within normal range indicating generally healthy animals,
The results of the treatment are set forth in Table ll.
TABLE I1 Weight Gain (gm) Group per rat in days A 10.6 B I4.U C 9.8 D 4.3
It can thus be seen that the animals on maltose gained almost 1 gm per day while the animals on glucose lost approximately 2 gm per day.
Alternatively, the results can be expressed in accordance with the following Table:
Male Sprague-Dawley rats weighing 330 gm each were divided into three groups of six rats. They were each fed gm daily of Rockland Chow. This was a greater restriction of food intake than in Example 1 since the animals were heavier. in addition to the oral feeding each animal received by intraperitoneal injection the following: 5 times daily Group A 3 ml of 0.45% sodium chloride Group B 3 ml of 5% glucose Group C 3 ml of 5% maltose After 4 days, the following weight changes were noted:
TABLE IV Weight loss (gm) Group per rat A 27 B 17 C 16 In this experiment the rats were given iso-caloric amounts of glucose and maltose. They reacted similarly in both cases. Groups B and C lost substantially less weight than the animals receiving only salt injections. This demonstrates that the maltose calories are equally available to the body as glucose calories.
EXAMPLE 3 Dogs initially weighing between 20 and 40 kg were divided into two groups. Group A was given as its total diet a 10% maltose solution containing 2 cc per 100 ml of McGaw Hyprotigen. Hyprotigen is a protein hydrolysate containing mixed amino acids and minerals. It is normally used as a supplement to glucose solutions. The animals were given, intravenously, cc of this solution per kg of body weight per day spread out over a period of 12 hours. Group B was treated the same as Group A except that the solution administered contained 5% glucose instead of 10% maltose.
The regimen was continued for three days after which Group A was switched to glucose and Group B was given the maltose. At the end of six days the reversal took place again.
The results of this test are set forth in the single FIG- URE annexed hereto and made a part hereof.
From the foregoing it can be seen that the novel method is useful as a replacement for glucose in the intravenous feeding of animals, including humans. It can constitute all or part of the total diet.
It is also especially useful when subcutaneous infusion is used in the treatment of infants suffering from dehydration and malnutrition. This occurs when an infant is suffering from an illness which causes vomiting or diarrhea.
The method is useful in cases of peritoneal dialysis wherein fluid is introduced into the peritoneal cavity in order to absorb poisons or the like from the system. The fluid is then withdrawn and replaced by fresh fluid until the treatment is complete. This treatment is also used to take the place of an artificial kidney machine when there is either lack of availability of such machine or the patient has only a mild kidney illness.
In addition, this method can be used in connection with full scale blood dialysis. Introduction of maltose into the dialyzing fluid enables the treatment to introduce calories into the bloodstream while, at thesame time, not increasing the osmotic pressure beyond normal levels. There is a tendency during dialysis toward loss of sugar from the blood. Previously 2 gm of glucose per liter of fluid was added in order to prevent this. If, as suggested herein, 1 gm of glucose is substituted by 2 gm of maltose (thus keeping the total osmotic pressure the same) the additional calories can be given.
As can be seen from the foregoing description the invention is to be broadly construed and not to be limited except by the character of the claims appended hereto.
What we claim is:
1. A method of nourishing a warm blooded animal comprising providing a solution of maltose in a pharmaceutically acceptable carrier, introducing said solution into said animals intraperitoneally, and then withdrawing said solution from said animal.
2. A method of nourishing a warm blooded animal comprising providing a solution of maltose in a pharmaceutically acceptable carrier, introducing said solution into a dialysing fluid, impinging blood from said animal on one side of a dialysis membrane, said dialysing fluid containing said solution being on the other side of said membrane, permitting said maltose to pass through said membrane into said blood, and then re-