Full text appears below.
Or download official US Patent Office image files of this
Tif files (best quality): page
1 page 2 page
3 page 4 page
If you have difficulties with TIF file format, we
recommend downloading and installing the AlternaTIFF
plug-in for Windows, Quicktime for MacIntosh, and Plugger for Linux.
Patent Number 4,971,951
Issue Date: Nov. 20, 1990
INSULIN POTENTIATION THERAPY
Inventors: Donato P. Garcia y Bellon, Mexico City, D. F., Mexico;
Donato P. Garcia, Jr., Nancalpan, Mexico;
SGA, Montreal, Quebec, Canada
AIDS & herpes
Appl. No.: 77,833 Filed: Jul. 27, 1987
Foreign Application Priority Data
Jun. 15, 1987 [CA] Canada ... 539,603
Int. Cl.... A6lK 37/26
U.S. Cl. ... 514/3; 514/4
Field of Search ... 514/3, 4
U.S. PATENT DOCUMENTS
2,145,869 2/1939 Garcia ... 514/23
Primary Examiner---Nathan M. Nutter
Attorney, Agent or Firm---Melvin K. Silverman
A new method of treatment of viral diseases, such as cancers and AIDS by intravenous
injection of insulin to induce hypoglycemia, followed by parenteral injection of glucose,
mixed with or in conjunction with, prescribed anti-viral/antineoplastic drugs. The
composition of the adjuvant and therapeutical drugs are also disclosed.
19 Claims, No Drawings
INSULIN POTENTIATION THERAPY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to a new method of treatment of
viral diseases. More specifically, this invention relates to a method employing a new
adjuvant for treating viral diseases, and new compositions for carrying out such
2. Description of Prior Art
Various carriers, adjuvants or agents have been used to enhance the
absorption or to potentiate the effect of drugs administered to patients for treatment of
specific diseases. An adjuvant to potentiate insulin for treatment of diabetes has been
disclosed in U.S. Pat. No. 4,277,465. U.S. Pat. No. 4,196,196 discloses a composition of
insulin, glucose and magnesium dipotassium ethylene diamine tetraacetic acid to enhance
tissue perfusion and to facilitate a divalent/monovalent cation gradient. A third U.S.
Pat. No. 2,145,869, discloses a composition including insulin and glucose for treatment of
However, it has not heretofore been known to treat viral diseases by
administration to a patient of insulin to induce hypoglycemia, followed by administration
of glucose and a specific drug directed at the treatment of a viral disease, nor have
compositions for such treatment been disclosed.
SUMMARY OF THE INVENTION
This invention relates to a novel method of treatment of viral
diseases on an intracellular level by inducing hypoglycemia by administration of insulin
and subsequent administration, during the state of hypoglycemia, of glucose and a specific
prescribed drug directed at a specific viral disease.
This invention also relates to a method of treatment of viral
diseases by administering drugs in lower dosages than would ordinarily be required for
effective treatment in the absence of the insulin/glucose treatment of this invention.
The present invention relates to the treatment of diseases such as
are considered by the state of the art in medical understanding to be virally-related, and
in which the cells involved in these disease processes are said to be virally-affected.
For the purposes of this invention, a virally affected cell is one that has been induced
into malignant transformation (cancer) by the action of a virus, or has been directly
infected and functionally destroyed by a virus. According to this present definition of
terms, the term "antiviral drug" is broadened in its scope to include the
variety of antineoplastic or anticancer drugs. The present invention specifies but is not
limited to the above described virally related disease processes.
The present invention further relates to treatment of specific viral
diseases such cancers and acquired immune deficiency syndrome (AIDS).
This invention in one aspect relates to a systemic adjuvant for
potentiating the drug to be effectively absorbed by the virally infected cells, which
comprises insulin and glucose and in another aspect, to new compositions of said adjuvant
and the drug prescribed for the particular disease.
DETAILED DESCRIPTION OF THE INVENTION
It is well known that the hormone insulin regulates the carbohydrate
metabolism, the synthesis of protein and of RNA, and the formation and storage of neutral
lipids. Thus synthetic insulin is administered to the diabetic patients to aid the
metabolism of glucose. It has now been found that insulin also increases cell membrane
permeability. The treatment of the present invention is thus named Insulin Potentiation
Therapy, hereinafter referred to as IPT.
Experimental observations support a theory that insulin will enhance
the permeability of cell membranes to glucose and other sugars. Moreover, this increased
permeability is not limited to sugars, but includes other solutes such as drugs. This
increased permeability induced by insulin furthermore permits the removal of waste
products from intracellular fluid (ICF) into the extracellular fluid (ECF), and more
importantly, to transfer the drug molecules from the ECF to the ICF, thus potentiating the
effects of administered drug.
It has also been found that in viral diseases such as various
cancers and AIDS, the viral cells in the active growth stage are most receptive to drugs.
Therefore, it is most effective to treat the disease at this stage.
It has been established that the virally affected cells targeted for
treatment in IPT (cancer cells for malignancy; lymphocytes and brain cells for AIDS)
possess insulin receptors on their cell membranes. Thus these cells would be amenable to
insulin's potentiating effect. It is to be understood that the virally affected cells
herein referred to include cancer cells as well as cells susceptible to attack by the AIDS
virus (human immunodeficiency virus-HIV) which includes principally the aforementioned
lymphocytes (specifically the T4 helper subset of lymphocytes) and brain cells.
In accordance with the present invention, a systemic adjuvant is
defined as an adjuvant to potentiate the migration of a drug through cell membranes, which
includes insulin in the amount of one unit per 10 kg of body weight to induce a mild state
of hypoglycemia, and a dose of glucose in the amount of about 20-50 cc of 50% hypertonic
The insulin used in the IPT treatment is regular crystalline insulin
solution, 100 units/cc. The glucose may either be injected as a mixture with the drug, or
separately immediately before injection of the prescribed drug.
The effect of the IPT treatment is two-fold: first, the cell
membranes of the virally affected cells are rendered more permeable by the insulin and
thus more receptive to the administered drugs; secondly, the administered glucose, in one
aspect, restores the patient's glucose equilibrium and, in another aspect, maximizes
absorption of the drug through the cell membranes by virtue of the ECF to ICF diffusion
gradient this hypertonic glucose injection causes. It has been demonstrated by in vitro
experiments with human breast cancer cells that the cytotoxic effect of the antineoplastic
drug methotrexate is increased ten-thousand-fold when used in conjunction with insulin.
Breast cancer cells also showed an increased capacity to accumulate free intracellular
methotrexate in the presence of insulin.
Ribavirin is an antiviral agent that has been used in the treatment
of early HIV infection (1ymphadenopathy syndrome, AIDS-Related-Complex, or ARC). These are
considered to be pre-AIDS conditions. Used in the conventional way, Ribavirin has not been
found effective in the treatment of established AIDS disease. This is because effective
concentrations of drug within the brain only develop after long term therapy when toxic
side effects start to play a limiting role for the use of the drug.
Some antiviral/antineoplastic drugs currently on the market include
cyclophosphamide, methotrexate and 5-flourouracil. These drugs all have toxic side
effects. The most serious, sometimes fatal, side effects are immune suppression, anemia
and gastrointestinal hemorrhage. Therefore, the use of these antineoplastic drugs involves
high risk. IPT, in accordance with the present invention, reduces such risks because under
the effect of insulin, the antiviral drug dosage may be greatly reduced.
The following table shows a comparison of drug dosages with IPT and
with chat of conventional treatment.
||Dosage with IPT
||one treatment 30 mg IV plus 200 mg tablet
orally daily for 6 days
Total = 1,230 mg/week
|400 mg tablets twice per day for 7 days
Total = 5,600 mg/week
||one treatment - 50-100 mg IV plus 100 mg
tablet daily for 6 days
Total = 650-700 mg
in 7 days
|Total = 3,500 mg
in 5 days
||one treatment - 1.25-2.5 mg IV plus 2.5 mg
tablet daily for 6 days
Total = 16.25-l7.5 mg in 7 days
|10-25 mg tablet daily for 7 days
Total = 70-175 mg in 7 days
||one treatment - 4 mg IV plus 4 mg tablet
daily for 6 days
Total = 28 mg in 7 days
|84 mg daily for 4 days
Total = 336 mg/4 days
The above table is based on body weight, 70 kg.
The method of treatment, in general, involves administering a dose
of 4-8 units of insulin, more specifically, one unit of insulin per 1O kg of body weight,
by intravenous (IV) injection. The patient is in the fasting state. The patient is closely
observed for insulin side effects. After 20 minutes of observation, and establishment of
induced hypoglycemia, 20-50 cc of 50% of hypertonic glucose is injected intravenously in
conjunction with, or mixed with, the prescribed drug in the dosage described above.
The potentiation of antiviral drug therapy is the primary intent of
IPT treatments. Other drugs directed at the simple alleviation of the symptoms of disease
may also be given during treatments. These drugs too are given in reduced dosages, orally,
intramuscularly, and intravenously, 20 minutes after the insulin injection. In addition to
the drugs necessary for treatment of viral infection, nutritional supplements such as
minerals, and vitamins may be administered to the patient. The IPT treatment is given
weekly followed by evaluation and testing to determine the progress of the treatment.
Between treatments, the patient is given oral antiviral antineoplastic drug for the six
days while resting at home.
The application of IPT to the specific disease, AIDS, has just been
tested in clinical cases. It has been established that the AIDS virus causes a profound
disruption of the immune system by infecting and inactivating the T4 helper lymphocyte
population. The AIDS virus also affects brain tissue, which has important implications for
the persistence of the disease in infected human beings. As described elsewhere, IPT is
ideally suited to overcoming this special problem in AIDS.
Thus far, only a handful of anti-AIDS drugs have been tested with
various degrees of success: azidothymidine, Ribavirin, Suramin and HPA-23. The primary
mode of action of these drugs is the blocking of the enzyme Reverse
enzyme is necessary for replication of the AIDS virus.
The present invention greatly improves the efficacy of such drug
treatment by potentiating the drug with insulin and glucose, thus reducing the required
drug dosage and toxicity and allows prolonged treatment with the drug. Most importantly
for AIDS, IPT allows these drugs free access to the AIDS virus infecting the brain tissue.
Eradication of this focus of virus is essential for complete treatment of AIDS.
The IPT treatment for AIDS is similar to that outlined above with
respect to cancer therapy. Insulin is administered intravenously first, followed by
administration of glucose and an effective amount of anti-AIDS drug. Additional antibiotic
and antineoplastic drugs may be concurrently administered. The treatment is carried out
weekly, but may be carried out twice a week when necessary. Oral drugs are taken daily
during the remaining days of the week.
The systemic adjuvant, one unit/10 kg body weight of insulin and
20-50 cc of 50% hypertonic glucose as described hereinbefore, in combination with an
antiviral drug, whether it be antineoplastic or anti-AIDS, constitutes a new composition
for treatment of virus disease.
It should be noted that not every patient is a candidate for IPT
treatment. Pregnant women, diabetics and children under the age of three are not suitable
patients for such treatment.
The IPT treatments are now described in the following clinical cases:
CASE l; INFILTRATING ADENOCARCINOMA OF THE BREAST
A 53-year-old female had a right breast cancer since May 23, 1985
without treatment. By August, 1986, the breast cancer had developed into a swelling with
foul-smelling discharge which caused pain and immobility in her right arm. She had weight
loss and low-grade fever. Her weight at the time of treatment was 73.4 kg.
A series of weekly IPT treatments was initiated. Seven units of
insulin were injected intravenously. After 20 minutes, she was given 50 cc of 50% of
hypertonic glucose, 10 mg of cyclophosphamide and 1.25 mg of methotrexate, by intravenous
injection. For six days during the week between IPT treatments, the patient took 100 mg of
cyclophosphamide orally each day. After the fifth IPT treatment, 4 mg of 5-flourouracil IV
was added to the weekly drug regimen.
Concurrently in these treatments, other drugs such as antibiotics,
vitamin B complex and vitamin C and calcium gluconate were also administered either orally
or parenterally. After the tenth treatment, a mammogram was taken which showed a slight
thickening of the skin in the right retroareolar area; no calcification or tumor masses
were identified. There was some thickening of the skin of the right breast, but no
palpable masses in either breast. The cervical, supraclavicular and axillary
lymphadenopathy were likewise no longer palpable. The patient's right arm had returned to
its normal size and color and was fully functional. The patient continued with follow-up
examinations and has shown no evidence of recurrence of breast cancer since April of 1987.
CASE 2: ADENOCARCINOMA OF THE LUNG
A 45-year-old non-smoking female suffered from adenocarcinoma of the
lung in the left lower lobe, classified as stage III. Weekly IPT treatment started on Nov.
12, 1985, with 6 units of insulin injected intravenously, followed by 20 cc of 50%
hypertonic glucose and 1.24 mg of methotrexate and 10 mg of cyclophosphamide. After the
8th weekly treatment, a daily tablet of 100 mg of cyclophospbamide was prescribed. A chest
X-ray showed a significant reduction of the left lower lobe lesion with a disappearance of
the satellite lesion. A year later, a follow-up X-ray showed almost complete clearing of
the lesion in the left lower lobe of the lung.
CASE 3: CARCINOMA OF THE CERVIX
A 22-year-old female suffered from abdominal pain, dysuria,
leukorrhea and intermenstrual bleeding. She was diagnosed to have a carcinoma of the
cervix mixed with adenoacanthoma grade II. Nine treatments were given once a week for nine
weeks. Five units of insulin were given followed by 50 cc of 50% hypertonic glucose and
100 mg of cyclophosphamide. Antibiotics, B complex and steroid were given as needed. At
the end of the ninth treatment, a Pap smear test was negative; and a biopsy indicated
chronic cervicitis with leukoparakeratosis and foci of squamous metaplasia but no signs of
anaplasia. Sixteen years later, a normal pregnancy and delivery were completed.
CASE 4: EWING'S SARCOMA OF THE BONE
A three-year-old female child had suffered a wrist fracture. At the
time of removal of her cast, gross deformity of the distal radius on her left wrist was
diagnosed as Ewing's tumor of the bone. An X-ray showed metastatic lesions were already
present in other bones.
The parents of the child were told that Ewing's tumor of the bone in
an advanced stage has no cure. Nevertheless, the parents brought the child for a trial
IPT. IPT treatment was started with 5 units of insulin, followed by 30 mg of
cyclophosphamide in conjunction with 50 cc of 50% of hypertonic glucose.
A total of seventeen weekly treatments was given. At the midpoint of
the patient's treatment, her X-ray showed good bone neo-formation with reestablishment of
a more normal contour to the distal radius. Upon completion of the 11th treatment, the
child was clinically well and has since lived a healthy life.
CASE 5: AIDS WITH HERPES ZOSTER
A 47-year-old homosexual male had been diagnosed by two successive
positive HTLV III antibody tests to have AIDS. IPT started on Nov. 25, 1986. The patient
had complaints of recurrent herpes zoster infection on the left side of his head and neck,
painful cervical lymphadenopathy, fever, malaise, weakness, diarrhea, headache,
irritability, poor memory, depression, and a weight loss of 15 kg over the preceding 6-8
weeks. Examination revealed single 2-cm nodes palpable in each axilla. A 2-cm node was
palpable in the right groin.
On Nov. 27, 1986, IPT treatment was started twice a week. Six units
of insulin were given intravenously; after a 20-minute interval, 30 mg of Ribavirin mixed
with 50 cc of 50% hypertonic glucose was injected intravenously. Antineoplastic drugs,
cyclophosphamide (10 mg) and Methotrexate (0.5 mg) along with vitamin B complex were
concurrently administered. On non-treatment days, the patient took 200 mg Ribavirin
orally, daily, along with any necessary drugs prescribed. At the end of the third
treatment the patient's fever, headaches, diarrhea, poor memory and depression
disappeared. The patient reported feeling well in all respects, and has resumed his normal
activities. On examination, the herpes zoster had cleared, the swellings in his neck were
no longer visible, and there was no palpable lymphadenopathy in the neck, and he had
gained 7 kg. As of Mar. 3, 1987, the HTLV III assay remains positive, the total T4
lymphocyte count is 233, and T4:T8 ratio is 0.45. The patient remains under active
treatment with regularly scheduled follow-up laboratory testing.
It is evident from the clinical cases, that the synergistic effect
of insulin and glucose in potentiating the drug directed at these virally-related
diseases, at a predetermined dosage is surprising and unprecedented.
Numerous modifications and variations of the present invention are
possible in light of the above teaching, and therefore, within the scope of the appended
claims; the invention may be practiced otherwise than as particularly described.
1. A method for treatment of viral diseases in a human, comprising: administering to
said human suffering therefrom an effective dose of insulin to induce mild hypoglycemia,
and thereafter administering a predetermined dose of glucose and a prescribed anti-viral
2. The method of claim 1 being carried out on a weekly basis.
3. The method of claim 1 wherein insulin is administered at a dose of one unit per 1O
kg of body weight.
4. The method of claim 1 wherein said glucose is about 20-50 cc of 50% hypertonic
5. The method of claim 1 wherein said anti-viral drug is selected from the group
consisting of cyclophosphamide, methotrexate, 5-flourouracil, azidothymidine, ribavirin,
surmarin and HPA-23.
6. A systemic adjuvant for potentiation of anti-viral drug comprising an effective
amount of insulin to induce hypoglycemia and a subsequent dose of glucose.
7. The systemic adjuvant of claim 6 wherein said insulin is one unit per 10 kg of body
weight and said glucose is about 20-50 cc of 50% hypertonic glucose.
8. A pharmaceutical composition, comprising: insulin--about one unit per 1O kilogram of
body weight; glucose--fifty percent solution, in the range of about twenty to about fifty
cubic centimeters; and a prescribed amount of an antineoplastic drug.
9. The composition of claim 8 wherein said antineoplastic drug is selected from the
group consisting of cyclophosphamide, methotrexate and 5-flourouracil.
10. A pharmaceutical composition, comprising: insulin--about one unit per 10 kilograms
of body weight; glucose--fifty per cent solution, in the range of about twenty to about
fifty cubic centimeters; and a prescribed amount of an anti-AIDS drug.
11. The composition of claim 10 wherein said anti-AIDS drug is selected from a group of
azidothymidine, ribavirin, suramin and HPA-23.
12. The method of claim 1 wherein the viral disease is AIDS, and said treatment being
carried out twice a week.
13. The composition of claim 9 wherein cyclophosphamide is about 50-100 mg.
14. The composition of claim 9 where methotrexate is in the amount of 1.25-2.5 mg.
15. The composition of claim 9 wherein 5-flourouracil is in the amount of 2-5 mg.
16. The composition of claim 11 wherein said ribavirin is in the amount of 30 mg.
17. The method as recited in claim 3 in which said administering step comprises the
step of intravenous administration.
18. The method as recited in claim 4 in which said step of administration composes the
step of intravenous administration.
19. The method as recited in claim 5 in which said step of administering comprising the
step of intravenous administration.
[Note: this document has been scanned and transcribed
by optical character recognition. Errors may have been made in transcription.]
(Return to top of page)