U.S. patent number 3,911,915 [Application Number 05/286,409] was granted by the patent office on 1975-10-14 for dialytic introduction of maltose into bloodstream.
This patent grant is currently assigned to Albert Einstein College of Medicine. Invention is credited to Giuseppe Rettura, Eli Seifter.
United States Patent |
3,911,915 |
Seifter , et al. |
October 14, 1975 |
Dialytic introduction of maltose into bloodstream
Abstract
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.
Inventors: |
Seifter; Eli (New Hyde Park,
NY), Rettura; Giuseppe (Bronx, NY) |
Assignee: |
Albert Einstein College of
Medicine (New York, NY)
|
Family
ID: |
23098472 |
Appl.
No.: |
05/286,409 |
Filed: |
September 5, 1972 |
Current U.S.
Class: |
604/4.01;
210/646; 604/28; 128/DIG.3; 514/23; 604/29 |
Current CPC
Class: |
A61M
5/00 (20130101); A61M 1/1654 (20130101); A61M
1/287 (20130101); Y10S 128/03 (20130101) |
Current International
Class: |
A61M
1/16 (20060101); A61M 5/00 (20060101); A61M
005/00 (); A61M 001/03 () |
Field of
Search: |
;424/180
;128/214R,214.2,213,DIG.3 ;23/258.5 ;210/22,321 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Truluck; Dalton L.
Attorney, Agent or Firm: Bierman & Bierman
Government Interests
The invention described herein was made in the course of work under
a grant or award from the Department of Health, Education, and
Welfare.
Claims
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 returning said
blood into said animal.
Description
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 patients 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 (10 -
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 10% 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 intravenously,
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 Sprague-Dawley 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 I ______________________________________ Protein Intake
Calorie Intake Group (gm per rat per day) (per rat per day)
______________________________________ A 5.3 100 B 2.1 40 C 2.1 40
D 2.1 40 ______________________________________
As a dietary supplement, Group B (the controls) were given 2.5 ml
of water by intraperitoneal injection 5 times daily. Group C was
given the same amount of a 7% glucose solution in the same manner.
Group D was given the same amount of a 14% maltose solution in the
same manner.
The glucose and maltose solutions were iso-osmotic and, therefore,
represent the limiting factors in the amount of each sugar which
can be introduced. It will 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 II.
TABLE II ______________________________________ Weight Gain (gm)
Group per rat in 5 days ______________________________________ A +
10.6 B - 14.0 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:
TABLE III ______________________________________ Calories ingested
Calories infused Weight gain Group (per rat per day) (per rat per
day) (gm) per rat ______________________________________ A 100 0 +
10.6 B 40 0 - 14.0 C 40 34 - 9.8 D 40 68 + 4.3
______________________________________
EXAMPLE 2
Male Sprague-Dawley rats weighing 330 gm each were divided into
three groups of six rats. They were each fed 10 gm daily of
Rockland Chow. This was a greater restriction of food intake than
in Example 1 since the animals were 20% 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:
TAVLE 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, 100 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 FIGURE 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 the same 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.
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