CA2304869A1 - Method of medical treatment using uric acid or precursors thereof - Google Patents
Method of medical treatment using uric acid or precursors thereof Download PDFInfo
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- CA2304869A1 CA2304869A1 CA002304869A CA2304869A CA2304869A1 CA 2304869 A1 CA2304869 A1 CA 2304869A1 CA 002304869 A CA002304869 A CA 002304869A CA 2304869 A CA2304869 A CA 2304869A CA 2304869 A1 CA2304869 A1 CA 2304869A1
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- uric acid
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- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 title claims abstract description 77
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 229940116269 uric acid Drugs 0.000 title claims abstract description 77
- 238000011282 treatment Methods 0.000 title claims abstract description 18
- 239000002243 precursor Substances 0.000 title claims description 22
- 238000000034 method Methods 0.000 title claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 27
- 201000011510 cancer Diseases 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 241000124008 Mammalia Species 0.000 claims abstract description 16
- 208000030507 AIDS Diseases 0.000 claims abstract description 14
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 8
- 230000003612 virological effect Effects 0.000 claims abstract description 8
- 210000000987 immune system Anatomy 0.000 claims abstract description 7
- 230000003313 weakening effect Effects 0.000 claims abstract description 7
- 206010063493 Premature ageing Diseases 0.000 claims abstract description 6
- 208000032038 Premature aging Diseases 0.000 claims abstract description 6
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 210000002966 serum Anatomy 0.000 claims description 9
- 108020004414 DNA Proteins 0.000 claims description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 6
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 6
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- 150000007523 nucleic acids Chemical class 0.000 claims description 4
- 102000053602 DNA Human genes 0.000 claims description 2
- 229920002477 rna polymer Polymers 0.000 claims description 2
- 230000002265 prevention Effects 0.000 abstract description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 201000005569 Gout Diseases 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 4
- GWGLGTKSTGSWGQ-UPHRSURJSA-N (z)-4-(carbamoylamino)-4-oxobut-2-enoic acid Chemical compound NC(=O)NC(=O)\C=C/C(O)=O GWGLGTKSTGSWGQ-UPHRSURJSA-N 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
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- 231100000517 death Toxicity 0.000 description 3
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- 208000001640 Fibromyalgia Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
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- 208000020029 respiratory tract infectious disease Diseases 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 206010053240 Glycogen storage disease type VI Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
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- 206010033128 Ovarian cancer Diseases 0.000 description 1
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- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 206010038074 Rectal polyp Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000006851 antioxidant defense Effects 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009809 bilateral salpingo-oophorectomy Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012321 colectomy Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000002052 colonoscopy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 208000018555 lymphatic system disease Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000000754 myometrium Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 201000005163 papillary serous adenocarcinoma Diseases 0.000 description 1
- 208000024641 papillary serous cystadenocarcinoma Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 208000022075 polyp of rectum Diseases 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011539 total abdominal hysterectomy Methods 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Treatment or prevention of cancer, AIDS, infectious diseases, viral diseases, premature aging, depression, weakening of the immune system in a mammal by raising the level of uric acid in a person to about 300 to 500 µmol/l. Kit to monitor the levels of uric acid in a mammal requiring such treatment or liable to suffer from the above diseases is also disclosed.
Description
METHOD OF MEDICAL TREATMENT USING URIC ACID OR
PRECURSORSTHEREOF
The present invention relates to a method of medical treatment 5 using uric acid or precursors thereof. More particularly, the invention is concerned with a method for the treatment of a patient suffering from cancer, AIDS, an infectious disease, or a viral disease, premature aging, depression, or weakening of the immune system, using uric acid or precursors thereof. This treatment can also be used for preventing the l0 occurrence of the above diseases or conditions in a person which is liable to suffer from them.
A living organism has a defense system to fight cancer formation, cancerous tumors and metastatic lesions through the entire organism.
This system is genetically programmed and is affected by environmental 15 factors such as nutrition, medications and neutroceuticals , etc. One third of all individuals in the U.S.A. will develop cancer. Cancer is a second cause of death in the U.S.A. Half of the deaths are from three of the most common types of cancer: lung, breast and colon rectum.
On the other hand, the occurrence of malignancy in deaths in 20 patients with gout is only 11% as compared with 33% in non gouty patients (or general population). It was observed that patients with gout and/or patients with high normal levels (350 to 450 ~mol/1 or uric acid) without gout have substantially less or no cancer, significantly lower incidence of infections, live longer and appear much healthier than 25 patients whose uric acid is 300 ~mol/1 or less.
At the same time it was observed that patients with cancer (other than leukemia) had either low serum uric acid or below normal (between 140 and 230 ~mol/l. A subsequent analysis of the data relative to the levels of uric acid was made in 10 patients with AIDS. It was found out 30 that in 7 out of 10 patients the levels of uric acid were between 140 -220 ~mol/ and that 3 out of 10 patients had levels of uric acid between 350 - 450 ~,mol/1. The three patients whose uric acid was 350 - 450 ~mol/1 were doing extremely well and had no overt signs of AIDS.
It is also known that people with high uric acid levels are more prone to developing hypertension, heart disease (A.S.H.D.), kidney 5 stones and diabetes. However, this group can easily be treated with standard therapies which are available in the year 2000. These treatments can consist of diet manipulation, lipid lowering drugs, antithrombotic drugs such as Aspirin ° or other antiplatelet medication.
In addition, hypertension can easily be treated with antihypertensive 10 medications.
However, a large number of people with uric acid levels of 350 -450 ~mol/1 do not develop these problems. If gout does occur, it can also be treated with drugs that lower uric acid, and anti-inflammatory medications. These observations have been confirmed in a survey 15 where the incidence of neoplasms in families of patients with high levels of uric acid was studied. It was found that the incidence of cancer in parents and grand-parents of people with high uric acid was 17.4% as compared with more than 50% in those whose uric acid was between 160 - 250 ~mol/1 (which is the lower range of normal).
20 It was also observed that people with high levels of uric acid for example in the range of 350 - 450 ~mol/1 are less susceptible of catching viral or infectious diseases, of prematurely aging, of undergoing depression, of suffering from fibromyalgia, or a weakening of their immune system, than those with low normal levels of uric acid.
25 A hypothesis was even made in the prior art to the effect that uric acid may provide an antioxidant defense in humans against cancer (PNAS (USA),1 78: 6858 - 6862 (1981). However, it was not established in this reference, how to treat people against cancer using uric acid, and the hypothesis was never confirmed.
30 There is also a suggestion in the prior art to combine uric acid with a lymphokine or a cytotoxin, or with a tumor necrosis factor, or a colony stimulating factor to treat damage to cells, tissue or other body parts in a mammalian host (U.S. 5,508,031; 5,667,776 and 5,702,697).
The presence of uric acid is merely intended at protecting the person treated against damage caused by the therapeutic agent, and is not aimed 5 at curing cancer.
U.S. 3,105,009 discloses using maleuric acid to inhibit mitosis of tumor cells. It should be noted that maleuric acid is a substantially different compound than uric acid. Furthermore, this Patent teaches a direct contact of the tumor cells with maleuric acid, contrary to what is 10 proposed in the present invention.
U.S. 5,872,124 teaches using uric acid for treating a disease of the central nervous system, which may include AIDS. No indication is given of how to specifically use uric acid to achieve the desired result, except to propose an effective dose of uric acid. This Patent discloses a 15 treatment for neurological damage. More specifically, the Patent suggests to treat allergic encephalitis which may occur in AIDS, however, it does not suggests treating AIDS per se.
U.S. 6,028,076 discloses the use of specific purine derivatives which do not include uric acid to treat diseases against which interferon 20 is effective. This Patent deals with the treatment of random diseases, it does not teach a treatment for a specific disease.
It is an object of the present invention to provide a method for treating mammals suffering from cancer, AIDS, an infectious disease, or a viral disease using uric acid or precursors thereof.
25 It is another object of the present invention to provide a method of prevention whereby mammals susceptible of catching diseases such as cancer, AIDS, an infectious disease or a viral disease are treated with uric acid or a precursor thereof.
It is another object of the present invention to provide a method 30 for preventing mammals from premature aging, depression, fibromyalgia, or undergoing a weakening of their immune system, by treating them with uric acid or a precursor thereof.
In accordance with the present invention, there is provided a method for the treatment of a mammal suffering from cancer, AIDS, an 5 infectious disease, a viral disease, premature aging, depression, a weakening of the immune system, or for preventing the occurrence of same in a mammal liable to suffer from same, which comprises administering to said mammal, uric acid or a precursor thereof until the level of serum uric acid in said mammal is raised to about 300 to 500 l0 ~mol/l.
The precursor of uric acid which is preferred is a nucleic acid which comprises ribonucleic acid, deoxyribonucleic acid and brewer's yeast.
Uric acid or its precursor may be administered orally or 15 intravenously. In the case of uric acid, the preferred dose would be one which would increase the serum uric acid concentration to be between about 300 and 500 ~,mol/l. In the case of a precursor of uric acid, the preferred dose is between about 400 and 800 mg.
The invention is now illustrated by means of the following test 20 cases, all dealing with some forms of cancer. However, since mammals with high levels of uric acid do not generally suffer from other related diseases as mentioned above, it is reasonable to assume that the above treatment with uric acid or a precursor of uric acid, may apply to the other related diseases 25 Test case 1 The patient was a 52 year old Caucasian female who had breast cancer diagnosed in 1984. The same year, she had mastectomy and was found PGR positive. She was subsequently treated with chemotherapy and Tamoxifen. In 1997, she had metastatic pleural effusions and was 30 treated with Epirubicin and Taxol. In spite of treatments, her disease increased and she was treated with Xelodex. Nevertheless, the patient continued to deteriorate. In January 2000, her uric acid level was 186 ~mol/1 and in addition to her regiment she was started on high purine diet and uric acid precursors (RNA + DNA = brewer's yeast 1000 mg).
One month later, her uric acid improved to 224 ~,mol/1 and her weight 5 increased by 3 pounds. She also feels better and the progression of cancer appears to be clinically arrested.
Test case 2 The patient is a 46 year old Caucasian female. She was diagnosed with advanced cervix cancer. She was treated with combined l0 chemo/radiation protocol. She was improved but still complained of fatigue and lymphadenopathy in the inguinal area. Her uric acid has been fluctuating between 132 ~mol/1 to 178 ~mol/l. She was put on high purine diet plus precursor of uric acid (RNA + DNA + brewer's yeast - 500 tidy. Six weeks later, the lymph nodes in the inguinal area 15 are not palpable while her uric acid increased to 282 ~mol/1. Presently she feels stronger than she has been for 6 years. She is being followed regularly.
Test case 3 This patient is a 73 year old Caucasian male who presented a 20 prostate carcinoma which metastasized to lymph nodes. Upon examination he had a 6 cm lymph node in the Lt. inguinal area and his PSA was 58 which increased recently from 17. Uric acid was 208 ~mol/1. He was taking Zolodex 1 tab t.i.d. A supplement of nucleic acids was added at dose of 500 mg, three times a day. Two weeks later, 25 the lesion in groin decreased to 2 cm and uric acid increased to 240 ~mol/1. One month later, the lesion in the inguinal area was undetectable. His P.S.A. decreased to 21 and uric acid increased to 276 pmol/le. He feels stronger, able to cope well and is less anxious.
Test case 4 30 The patient is a 78 year old man with rectal polyps. The bleeding per rectum occurred during the last 6 months and the patient had colonoscopy to determine if the bleeding was secondary to neoplasm.
The biopsy revealed colonic neoplasm and the patient is scheduled for surgical resection. His uric acid was found to be 204 ~,mol/1. He was placed on a high purine diet and precursors of uric acid (RNA+ DNA +
5 brewer's yeast) 500 mg t.i.d., while awaiting surgery. Two weeks later, the serum uric acid went up to 284 and bleeding per rectum stopped.
The patient will undergo another conoloscopy and biopsy, but is presently reasonably well.
Test case 5 l0 The patient is a 58 year old Caucasian female who was diagnosed in 1997 with ovarian cancer, involving entire peritoneum. She had total abdominal hysterectomy, bilateral salpingo - oophorectomy, infracolic omentectomy, transverse colectomy and a biopsy of retrosigmoid nodule.
15 The pathological report was as follows: lymph nodes - metastatic carcinoma of myometrium, ovaries showed pooly differentiated papillary serous adenocarcinoma.
After surgery, the patient improved but in 1999, she developed matastasis to the cerebellum. In 1999, cerebellar metastasis were 20 removed surgically. Upon reviewing the case, it was noted that the serum uric acid levels were low normal: in 1997 it was 188 ~mol/1 and in 1999 uric acid was 182 ~mol/1. In February 2000, she was started on a high purine diet and uric acid precursors (RNA, DNA, Brewer's yeast, 500 mg t.i.d.). Six weeks later her serum uric acid rose to 264 ~mol/1 25 and she feels well. There is no evidence or recurrences. The patient is being monitored closely.
To summarize, people with uric acid levels above about 350 ~mol/1 appear younger, healthier, usually free of cancer and free of upper respiratory infections. It was also observed that patients with gout or 30 high uric acid experienced very few infections, days missed at work due to infections. As a result of these findings it is believed that monitoring serum uric acid levels and using either uric acid per se or precursors thereof such as nucleic acids to elevate serum uric acid to levels between 350 - 450 ~,mol/1 is beneficial in treatment and prevention of cancers, infections, AIDS, and other related diseases. Therefore, according to the 5 present invention, uric acid may be used as for example an antibiotic, an antiviral, an anti-cancer agent. Also uric acid can be used in prevention of cancer in patients with low uric acid levels and a high risk factor for cancer. Uric acid can also be used in prevention of frequent infections such as upper respiratory infections, AIDS and viral infections and also 10 depression.
Of course , it is within the scope of the present invention to use the above treatment for other disease than cancer such as those mentioned above, and to provide a kit for the determination of levels of uric acid in a mammal requiring such treatment or liable to suffer from 15 the above diseases.
PRECURSORSTHEREOF
The present invention relates to a method of medical treatment 5 using uric acid or precursors thereof. More particularly, the invention is concerned with a method for the treatment of a patient suffering from cancer, AIDS, an infectious disease, or a viral disease, premature aging, depression, or weakening of the immune system, using uric acid or precursors thereof. This treatment can also be used for preventing the l0 occurrence of the above diseases or conditions in a person which is liable to suffer from them.
A living organism has a defense system to fight cancer formation, cancerous tumors and metastatic lesions through the entire organism.
This system is genetically programmed and is affected by environmental 15 factors such as nutrition, medications and neutroceuticals , etc. One third of all individuals in the U.S.A. will develop cancer. Cancer is a second cause of death in the U.S.A. Half of the deaths are from three of the most common types of cancer: lung, breast and colon rectum.
On the other hand, the occurrence of malignancy in deaths in 20 patients with gout is only 11% as compared with 33% in non gouty patients (or general population). It was observed that patients with gout and/or patients with high normal levels (350 to 450 ~mol/1 or uric acid) without gout have substantially less or no cancer, significantly lower incidence of infections, live longer and appear much healthier than 25 patients whose uric acid is 300 ~mol/1 or less.
At the same time it was observed that patients with cancer (other than leukemia) had either low serum uric acid or below normal (between 140 and 230 ~mol/l. A subsequent analysis of the data relative to the levels of uric acid was made in 10 patients with AIDS. It was found out 30 that in 7 out of 10 patients the levels of uric acid were between 140 -220 ~mol/ and that 3 out of 10 patients had levels of uric acid between 350 - 450 ~,mol/1. The three patients whose uric acid was 350 - 450 ~mol/1 were doing extremely well and had no overt signs of AIDS.
It is also known that people with high uric acid levels are more prone to developing hypertension, heart disease (A.S.H.D.), kidney 5 stones and diabetes. However, this group can easily be treated with standard therapies which are available in the year 2000. These treatments can consist of diet manipulation, lipid lowering drugs, antithrombotic drugs such as Aspirin ° or other antiplatelet medication.
In addition, hypertension can easily be treated with antihypertensive 10 medications.
However, a large number of people with uric acid levels of 350 -450 ~mol/1 do not develop these problems. If gout does occur, it can also be treated with drugs that lower uric acid, and anti-inflammatory medications. These observations have been confirmed in a survey 15 where the incidence of neoplasms in families of patients with high levels of uric acid was studied. It was found that the incidence of cancer in parents and grand-parents of people with high uric acid was 17.4% as compared with more than 50% in those whose uric acid was between 160 - 250 ~mol/1 (which is the lower range of normal).
20 It was also observed that people with high levels of uric acid for example in the range of 350 - 450 ~mol/1 are less susceptible of catching viral or infectious diseases, of prematurely aging, of undergoing depression, of suffering from fibromyalgia, or a weakening of their immune system, than those with low normal levels of uric acid.
25 A hypothesis was even made in the prior art to the effect that uric acid may provide an antioxidant defense in humans against cancer (PNAS (USA),1 78: 6858 - 6862 (1981). However, it was not established in this reference, how to treat people against cancer using uric acid, and the hypothesis was never confirmed.
30 There is also a suggestion in the prior art to combine uric acid with a lymphokine or a cytotoxin, or with a tumor necrosis factor, or a colony stimulating factor to treat damage to cells, tissue or other body parts in a mammalian host (U.S. 5,508,031; 5,667,776 and 5,702,697).
The presence of uric acid is merely intended at protecting the person treated against damage caused by the therapeutic agent, and is not aimed 5 at curing cancer.
U.S. 3,105,009 discloses using maleuric acid to inhibit mitosis of tumor cells. It should be noted that maleuric acid is a substantially different compound than uric acid. Furthermore, this Patent teaches a direct contact of the tumor cells with maleuric acid, contrary to what is 10 proposed in the present invention.
U.S. 5,872,124 teaches using uric acid for treating a disease of the central nervous system, which may include AIDS. No indication is given of how to specifically use uric acid to achieve the desired result, except to propose an effective dose of uric acid. This Patent discloses a 15 treatment for neurological damage. More specifically, the Patent suggests to treat allergic encephalitis which may occur in AIDS, however, it does not suggests treating AIDS per se.
U.S. 6,028,076 discloses the use of specific purine derivatives which do not include uric acid to treat diseases against which interferon 20 is effective. This Patent deals with the treatment of random diseases, it does not teach a treatment for a specific disease.
It is an object of the present invention to provide a method for treating mammals suffering from cancer, AIDS, an infectious disease, or a viral disease using uric acid or precursors thereof.
25 It is another object of the present invention to provide a method of prevention whereby mammals susceptible of catching diseases such as cancer, AIDS, an infectious disease or a viral disease are treated with uric acid or a precursor thereof.
It is another object of the present invention to provide a method 30 for preventing mammals from premature aging, depression, fibromyalgia, or undergoing a weakening of their immune system, by treating them with uric acid or a precursor thereof.
In accordance with the present invention, there is provided a method for the treatment of a mammal suffering from cancer, AIDS, an 5 infectious disease, a viral disease, premature aging, depression, a weakening of the immune system, or for preventing the occurrence of same in a mammal liable to suffer from same, which comprises administering to said mammal, uric acid or a precursor thereof until the level of serum uric acid in said mammal is raised to about 300 to 500 l0 ~mol/l.
The precursor of uric acid which is preferred is a nucleic acid which comprises ribonucleic acid, deoxyribonucleic acid and brewer's yeast.
Uric acid or its precursor may be administered orally or 15 intravenously. In the case of uric acid, the preferred dose would be one which would increase the serum uric acid concentration to be between about 300 and 500 ~,mol/l. In the case of a precursor of uric acid, the preferred dose is between about 400 and 800 mg.
The invention is now illustrated by means of the following test 20 cases, all dealing with some forms of cancer. However, since mammals with high levels of uric acid do not generally suffer from other related diseases as mentioned above, it is reasonable to assume that the above treatment with uric acid or a precursor of uric acid, may apply to the other related diseases 25 Test case 1 The patient was a 52 year old Caucasian female who had breast cancer diagnosed in 1984. The same year, she had mastectomy and was found PGR positive. She was subsequently treated with chemotherapy and Tamoxifen. In 1997, she had metastatic pleural effusions and was 30 treated with Epirubicin and Taxol. In spite of treatments, her disease increased and she was treated with Xelodex. Nevertheless, the patient continued to deteriorate. In January 2000, her uric acid level was 186 ~mol/1 and in addition to her regiment she was started on high purine diet and uric acid precursors (RNA + DNA = brewer's yeast 1000 mg).
One month later, her uric acid improved to 224 ~,mol/1 and her weight 5 increased by 3 pounds. She also feels better and the progression of cancer appears to be clinically arrested.
Test case 2 The patient is a 46 year old Caucasian female. She was diagnosed with advanced cervix cancer. She was treated with combined l0 chemo/radiation protocol. She was improved but still complained of fatigue and lymphadenopathy in the inguinal area. Her uric acid has been fluctuating between 132 ~mol/1 to 178 ~mol/l. She was put on high purine diet plus precursor of uric acid (RNA + DNA + brewer's yeast - 500 tidy. Six weeks later, the lymph nodes in the inguinal area 15 are not palpable while her uric acid increased to 282 ~mol/1. Presently she feels stronger than she has been for 6 years. She is being followed regularly.
Test case 3 This patient is a 73 year old Caucasian male who presented a 20 prostate carcinoma which metastasized to lymph nodes. Upon examination he had a 6 cm lymph node in the Lt. inguinal area and his PSA was 58 which increased recently from 17. Uric acid was 208 ~mol/1. He was taking Zolodex 1 tab t.i.d. A supplement of nucleic acids was added at dose of 500 mg, three times a day. Two weeks later, 25 the lesion in groin decreased to 2 cm and uric acid increased to 240 ~mol/1. One month later, the lesion in the inguinal area was undetectable. His P.S.A. decreased to 21 and uric acid increased to 276 pmol/le. He feels stronger, able to cope well and is less anxious.
Test case 4 30 The patient is a 78 year old man with rectal polyps. The bleeding per rectum occurred during the last 6 months and the patient had colonoscopy to determine if the bleeding was secondary to neoplasm.
The biopsy revealed colonic neoplasm and the patient is scheduled for surgical resection. His uric acid was found to be 204 ~,mol/1. He was placed on a high purine diet and precursors of uric acid (RNA+ DNA +
5 brewer's yeast) 500 mg t.i.d., while awaiting surgery. Two weeks later, the serum uric acid went up to 284 and bleeding per rectum stopped.
The patient will undergo another conoloscopy and biopsy, but is presently reasonably well.
Test case 5 l0 The patient is a 58 year old Caucasian female who was diagnosed in 1997 with ovarian cancer, involving entire peritoneum. She had total abdominal hysterectomy, bilateral salpingo - oophorectomy, infracolic omentectomy, transverse colectomy and a biopsy of retrosigmoid nodule.
15 The pathological report was as follows: lymph nodes - metastatic carcinoma of myometrium, ovaries showed pooly differentiated papillary serous adenocarcinoma.
After surgery, the patient improved but in 1999, she developed matastasis to the cerebellum. In 1999, cerebellar metastasis were 20 removed surgically. Upon reviewing the case, it was noted that the serum uric acid levels were low normal: in 1997 it was 188 ~mol/1 and in 1999 uric acid was 182 ~mol/1. In February 2000, she was started on a high purine diet and uric acid precursors (RNA, DNA, Brewer's yeast, 500 mg t.i.d.). Six weeks later her serum uric acid rose to 264 ~mol/1 25 and she feels well. There is no evidence or recurrences. The patient is being monitored closely.
To summarize, people with uric acid levels above about 350 ~mol/1 appear younger, healthier, usually free of cancer and free of upper respiratory infections. It was also observed that patients with gout or 30 high uric acid experienced very few infections, days missed at work due to infections. As a result of these findings it is believed that monitoring serum uric acid levels and using either uric acid per se or precursors thereof such as nucleic acids to elevate serum uric acid to levels between 350 - 450 ~,mol/1 is beneficial in treatment and prevention of cancers, infections, AIDS, and other related diseases. Therefore, according to the 5 present invention, uric acid may be used as for example an antibiotic, an antiviral, an anti-cancer agent. Also uric acid can be used in prevention of cancer in patients with low uric acid levels and a high risk factor for cancer. Uric acid can also be used in prevention of frequent infections such as upper respiratory infections, AIDS and viral infections and also 10 depression.
Of course , it is within the scope of the present invention to use the above treatment for other disease than cancer such as those mentioned above, and to provide a kit for the determination of levels of uric acid in a mammal requiring such treatment or liable to suffer from 15 the above diseases.
Claims (8)
1. A method for the treatment of a mammal suffering from cancer, AIDS, an infectious disease or a viral disease, premature aging, depression, weakening of the immune system, or for preventing the occurrence of same in a mammal liable to suffer from same, which comprises administering to said mammal uric acid or a precursor thereof until the level of serum uric acid in said mammal is raised to about 300 to 500 µmol/l.
2. Method according to claim 1, which comprises administering uric acid.
3. Method according to claim 1, which comprises administering a precursor of uric acid.
4. Method according to claim, wherein said precursor of uric acid is a nucleic acid comprising ribonucleic acid, deoxyribonucleic acid and brewer's yeast.
5. Method according to claim 1, wherein said uric acid or precursor thereof is administered orally.
6. Method according to claim 1, wherein said uric acid or precursor thereof is administered intravenously.
7. Method according to claim 3, wherein said precursor is given at doses of between 400 and 800 mg.
8. Kit for the determination of levels of uric acid in a mammal suffering from cancer, AIDS, an infectious disease, a viral disease, premature aging, depression, and weakening of the immune system or liable to suffer from same.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002304869A CA2304869A1 (en) | 2000-04-07 | 2000-04-07 | Method of medical treatment using uric acid or precursors thereof |
| AU2001248173A AU2001248173A1 (en) | 2000-04-07 | 2001-04-04 | Use of uric acid or precursors thereof as a treatment for cancer, aids and the like |
| PCT/CA2001/000457 WO2001076606A2 (en) | 2000-04-07 | 2001-04-04 | Use of uric acid or precursors thereof as a treatment for cancer, aids and the like |
| CA002405591A CA2405591A1 (en) | 2000-04-07 | 2001-04-04 | Use of uric acid or precursors thereof as a treatment for cancer, aids and the like |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002304869A CA2304869A1 (en) | 2000-04-07 | 2000-04-07 | Method of medical treatment using uric acid or precursors thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2304869A1 true CA2304869A1 (en) | 2001-10-07 |
Family
ID=4165836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002304869A Abandoned CA2304869A1 (en) | 2000-04-07 | 2000-04-07 | Method of medical treatment using uric acid or precursors thereof |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU2001248173A1 (en) |
| CA (1) | CA2304869A1 (en) |
| WO (1) | WO2001076606A2 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5508031A (en) * | 1986-11-21 | 1996-04-16 | Cetus Oncology Corporation | Method for treating biological damage using a free-radial scavenger and interleukin-2 |
| WO1997039352A1 (en) * | 1996-04-15 | 1997-10-23 | Fox Chase Cancer Center | Assays for detection of purine metabolites |
| US5872124A (en) * | 1996-07-31 | 1999-02-16 | Thomas Jefferson University | Treatment of diseases of the central nervous system using uric acid as a scavenger of peroxynitrite |
| ATE352306T1 (en) * | 1998-07-31 | 2007-02-15 | Meir S Sacks | A COMPOSITION CONTAINING A PRECURSOR OF URIC ACID AND AN ANTIOXIDANT AND THE USE THEREOF FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
-
2000
- 2000-04-07 CA CA002304869A patent/CA2304869A1/en not_active Abandoned
-
2001
- 2001-04-04 AU AU2001248173A patent/AU2001248173A1/en not_active Abandoned
- 2001-04-04 WO PCT/CA2001/000457 patent/WO2001076606A2/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001248173A1 (en) | 2001-10-23 |
| WO2001076606A3 (en) | 2002-08-01 |
| WO2001076606A2 (en) | 2001-10-18 |
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