The drug solution side effects of anticancer agents

 

(57) Abstract:

The invention relates to medicine, namely to clinical pharmacology, in particular to the development of a new drug and method of reducing and/or eliminating the side effects of anticancer agents. The essence of the invention is the creation of a generic drug that not only has an antitumor effect, but also very effective in reducing the side effects of various anticancer agents as chemotherapy and radiology, as well as the essence of the invention is to provide a method of using such drug. The result is achieved by oral administration of squalene, which is activated by heat treatment or UV radiation, infrared radiation, or exposure to reactive oxygen species. The drug is used in an effective amount, optimally at a dose of 0.3 ml/kg of body weight, in cancer of the stomach, intestine, lung carcinomas endo - and accoules, leukemia. The technical result - expanding Arsenal of anticancer agents. 2 C. and 7 C.p. f-crystals, 1 table.

The invention relates to medicine, namely to clinical pharmacology, in particular to the creation of new PR the antitumor (or protivoblastomna) drugs are divided into several groups, on the basis of their chemical structure, mechanism of action, sources: alkylating agents, antimetabolites, antibiotics, agonists and antagonists hormones, alkaloids and other plant.

Along with specific inhibitory effect on the tumor, modern anti-cancer drugs act on other tissues and systems of the body that, on the one hand, leads to undesirable side effects, and on the other hand, you can use them in other areas of medicine. In addition, a significant drawback of modern drugs is the low selectivity of action against tumor cells.

One of the main side effects of anticancer chemotherapy is bone marrow suppression, which requires accurate control of the dose and mode of use of drugs; you need to consider that depression of haematopoiesis enhanced by combination therapy, combination drugs with radiation therapy and other frequent nausea, vomiting, loss of appetite, diarrhea, possible loss and other side effects. Some antitumor antibiotics have cardio (doxorubicin and others), nephro - and ototoxicity. When using the CTD is to hormonal disorders.

One of the characteristic features of many anticancer drugs is their immunosuppressive effect, which can weaken the body's defenses, to facilitate the development of infectious complications. At the same time, a number of anticancer agents (methotrexate, azathioprine, cyclophosphamide, cytarabine, prospidin and others) is used as immunosuppressants in autoimmune diseases.

Recently developed drug methods to improve the effectiveness and tolerability of anticancer drugs. So, calcium folinate allows you to optimize the action of methotrexate and other antimetabolites (including isomers), a new effective anti-emetics (blockers of serotonin 5-HT3receptors: ondansetron, tropisetron and others) to reduce nausea and vomiting, "colony-stimulating factors (filgrastim, molgramostim, and others) - to reduce the risk of neutropenia (encyclopedia of drugs, ed. 7, 2000, S. 1221).

Modern development of anticancer agents provide dosage forms that allow more selectively affect tumor, reducing the cytotoxic effect of the drug (U.S. Pat. USA 6207133, 22.03.2001).

In the present wrtv with specific tumor pathology, these include substances of animal origin (see, for example, U.S. Pat. RF 2099065, 1997) and plant origin (U.S. Pat. RF 2078578, 1997).

However, the known drugs are not universal for different tumor pathologies.

The technical task of the present invention is the creation of a generic drug that not only has an antitumor effect, but also very effective in reducing the side effects of various anticancer agents as chemotherapy and radioisotope. Object of the invention is the creation of a method of using such drug.

The problem is solved by the fact that created the drug on the basis of natural squalene, activate to acquire useful properties by heat treatment or ultraviolet (UV) radiation, infrared (IR) radiation, or exposure to reactive oxygen species. As a result of activation get activated squalene (AU), which is an oily liquid, having the following physico-chemical properties in comparison with native squalene (see table. It is given at the end of the description).

Activation of squalene is following on a period of 1-6 hours.

B. the Influence of UV radiation within 1-12 hours, optimally at a wavelength of 250-350 nm for 3-6 hours.

B. Exposure to IR radiation within 3-12 hours, optimally at a wavelength of 400-800 nm for 6-9 hours.

, The Influence of reactive oxygen species selected from the group of: ozone, hydrogen peroxide, transmission of molecular oxygen. The processed active form of oxygen is carried out from 3 to 24 hours.

When working on the present invention we studied in detail and presents the optimal stimulation modes to achieve maximum positive results.

Detail antitumor properties of activated squalene (AU) as an independent product and method thereof are described in detail in the previously filed application 2001113007 (16.05.2001). The present application describes the combined use of speakers with other known anticancer remedies where as exhibiting the properties of the drug, debilitating and/or eliminating and accelerating effect of anticancer agents as chemotherapy and radiology.

The drug is an activated squalene, i.e. activated by heat treatment, UV radiation, E or slightly yellowish viscous liquid, having a boiling point of 238-240oWith and share 0,853-0,855.

The use of the drug can be carried out simultaneously with the holding of chemo - and radiotherapy by known means, may be used as well known means to reduce the occurrence of side effects, and is already treated patients with manifestation of the latter side effects of chemotherapy and/or radiotherapy.

Another aspect of the present invention is a method of reducing and/or eliminating the side effects of chemo - and radiotherapy of tumors. The method is that the patient is prescribed as in an effective amount.

The drug given orally to obtain the desired effect. The optimal dose is the dose of 0.3 ml/kg of body weight. Duration of appointment may vary from 7 to 200 days, in many cases, the effect is achieved within 7 to 20 days. The drug test was conducted on more than 300 patients with various tumor pathology when used as chemo-and radiotherapy agents.

The drug is effective in deformities such as tumors of the stomach and intestines, lung, adenocarcinomas Exo - and endocrine glands, the metastasis of various tumors, leukemia and other opuholei R. for 65 years, stomach cancer, was admitted to the surgical hospital in the state of moderate severity, with complaints of weakness, fatigue, malaise, nausea, vomiting after eating, expressed intense pain in the abdomen without precise localization.

Ill for the last 8 months, when on a background of full health appeared nausea, General weakness, then joined the expressed painful syndrome, nekupiruemy taking non-narcotic analgesics. When examination revealed generalized tumor process - cancer of the antrum of the stomach, adenocarcinoma N11 with the spread process on the peritoneum - cancerosas. Case recognized inoperable. The chemotherapy.

When viewed in hospital - conscious, inhibited, the contact becomes reluctantly, negative to medical staff. The skin is a normal color, turgor is reduced, hypotrophy of muscles and subcutaneous tissue. Abdomen moderately increased in size, symmetrical, slightly swollen, painful during deep palpation in the epigastrium. The liver is at the edge of the costal arch.

Pronounced syndrome were stopped by the introduction of narcotic analgesics (morphine, omnopon) up to 7-8 times a day. The patient noted the complete absence amicin) every 3 days intravenously (12 receptions) increased nausea, vomiting, pain. Appeared tradecopier pain in the heart, increased weakness. Laboratory records showed a picture of oppression blood (leukocytes reduced from 5.2 to 3.4 thousand.) and development of iron deficiency anemia. The liver was increased to 2.5 cm from the costal arch. Additional introduction of speakers at a dose of 0.3 ml/kg of body weight made it possible to neutralize the symptom of toxemia.

From the 6th day noted a decrease in pain in the abdomen (became quite 1 injection of narcotic analgesic). By the end of the 7th day completely disappeared phenomenon dyspepsia (nausea and vomiting, pain in the liver, appetite). To the 30-th day there was a normalization of blood counts.

On the 25th day from the start of the reception speaker (on the back of continued chemotherapy) completely pain disappeared, and was neutralized phenomena cardiopathy. The drug was continued for 120 days, after which the patient was discharged in satisfactory condition.

Conclusion: speakers at a dose of 0.3 ml/kg not only eliminates the negative effects of chemotherapy, but also relieves the symptoms of cancermatch.

Example 2.

Patient W., 58 years, colorectal cancer, was admitted to the surgical hospital with complaints of General weakness, moderate bleeding (up to 5 times WH">

When the survey was found bleeding tumor of the rectum at 8 cm from the anal verge by size 3 x 5 cm with metastases in lymph nodes and peritoneum. The diagnosis of well-differentiated adenocarcinoma with metastasis to the liver, peritoneum and lymph nodes. Case recognized inoperable and the patients assigned to chemotherapy is the main drug - Platin, at a dose of 150 mg daily. Other means - vinblastine (6 mg) was administered to 7-day intervals. The full course of treatment - 30 days, after which it was interrupted treatment. After a 20-day break, they were re-rate.

Already at the beginning of the 2nd course noted the following symptoms: loss of appetite, hearing loss, weakness, reduced temperature. Laboratory tests revealed leukemia (up to 2.2 thousand white blood cells), thrombocytopenia, decreased number of red blood cells up to 2 million, etc., the Bleeding increased. Overall pain is not significantly changed.

The purpose of this period of the AC at a dose of 0.3 ml/kg of body weight quickly changed the picture of the disease. Pain syndrome was neutralized within 10 days of receiving the drug. The bleeding stopped on the 7th day, in spite of the continuation of chemotherapy, the white blood cell count increased (50-day) to 4.1 thousand, erythrocytes - up to 2.5 million, tro is the possibility to continue chemotherapy.

Conclusion: speakers at a dose of 0.3 ml/kg and eliminates the negative effects of chemotherapy, and symptoms of cancermatch.

Example 3.

Patient S., 38 years old, metastatic disease of the right lung, was admitted to the hospital for the next course of chemotherapy with complaints of weakness, nausea, vomiting, dizziness, common baldness, numerous subcutaneous hemorrhage.

Six years ago, diagnosed with Adenocarcinoma of the cervix. Surgery - total removal of the uterus and ovaries, and then was allowed for stabilization of the process. However, 5 months ago, the patient had increasing weakness. Appeared hemoptysis. Computed tomography of the lungs revealed 4 metastasis in size from 0.3 to 1.5 square cm, held on 3 courses of chemotherapy (combination doxorubicin hydrochloride and vinblastine), then the phenomenon of toxicity significantly increased, and the size of the metastases was increased to 3 square, see the blood - leukopenia, thrombocytopenia, anemia. The platelet count decreased to 50 thousand , which led to numerous hemorrhages. The purpose of the AC at a dose of 0.3 ml/kg of body weight during the 30 days allowed to eliminate negative changes and to continue chemotherapy. Re-examination of lungs (F) research has documented the process stops. Just sick during the year received 8 cycles of chemotherapy. Despite this, the patient began the growth of hair, completely disappeared weakness, stopped subcutaneous hemorrhage.

Conclusion: the combination of speakers with chemotherapy drugs not only reduces the toxic manifestations of the latter, but also enhances the antitumor effect of chemotherapy.

Example 4.

Patient R., 70 years. Diagnosis: Adenocarcinoma of the prostate stage 3 (Gleason) with metastases in lymph nodes and bone. Was admitted to the hospital for radiotherapy.

Sick for more than 2 years, when I noticed the urination and pain in the lower abdomen. Ultrasound and palpation revealed the presence of a large tumor with metastasis to the nearest lymph node. A biopsy of the tumor was allowed to make a diagnosis: Adenocarcinoma of the prostate. Case recognized inoperable and patients received 6 courses of chemotherapy (estrace, mitoxantrone). But pain and most of the signs of the disease could not be cured. On the contrary, appeared back pain and symptoms of chronic renal and liver failure.

degree of pain. However, after a month of starting treatment of the phenomenon of renal-hepatic insufficiency increased number of leukocytes decreased from 3.5 to 2 thousand, platelet - 1.6 times.

The purpose of activated squalene (AC) at a dose of 0.3 ml/kg of body weight of the patient resulted in the complete elimination of pain already after 14 days from the start of treatment. When this is normalized indicators of liver function (transaminases) and the volume of the body decreased appetite. By the end of the month from the beginning of treatment the patient has gained 2 kg weight. After 60 days of treatment, the number of leukocytes in the blood increased to 4.8 thousand, while the number of prostatic specific antigen decreased from 22 to 6 ng/ml

Performed after 3 month ultrasound. Identified the reduction of tumor volume by 22%. Re-introduction of radionucleotides in patients receiving ACE has allowed to reduce the amount of antigen to 4 ng/ml.

Conclusion: the preparation of the AU appointed in a dose of 0.3 ml/kg of body weight, not only eliminates the symptoms of intoxication caused by the introduction of radionucleotides, but also has anti-tumor effect.

Thus, the proposed remedy and method to mitigate and/or eliminate side effects protivoopujolevoe therapy.

1. The drug, debilitating and/or eliminating the side effects of anticancer agents based on natural organic compounds, characterized in that as a natural compound contains squalene, which is activated by heat treatment or UV radiation, infrared radiation, or exposure to reactive oxygen species, the product is a colorless or yellowish viscous liquid with a boiling point 238-240oWith and share 0,853-0,855.

2. The drug under item 1, characterized in that it is activated by heat treatment at to= 90oC, or UV radiation at a wavelength of 250-350 nm for 3-6 h, or by exposure to infrared radiation at a wavelength of 400-800 nm for 6-9 h, or exposure to reactive oxygen species within 3-24 hours

3. The drug PCP.1 and 2, characterized in that it is effective in cancer of the stomach, intestine, lung carcinomas endo - and exocrine gland, leukemia, metastasis of various tumors.

4. The drug under item 1, characterized in that it reduces and/or eliminates the side effects of chemotherapy and/or radioisotope funds.

5. Method of reducing and/or eliminating the side effects of anticancer CPE is of an unforgettable, characterized in that the patient is given a drug, characterized in PP.1-4, in an effective amount.

6. The method according to p. 5, characterized in that conduct mitigation and/or elimination of side effects of chemotherapy and/or radioisotope preparations.

7. The method according to PP.5 and 6, characterized in that the drug is used at a dose of 0.3 ml/kg of body weight for humans.

8. The method according to PP.5-7, characterized in that the drug is administered per os in a period of time sufficient to mitigate and/or eliminate side effects.

9. The method according to p. 8, characterized in that the drug is administered at a dose of 0.3 ml/kg for 7-200 days for a person.

 

Same patents:

The invention relates to a method of separation of para-xylene from a feedstock containing a mixture of aromatic C8isomers

The invention relates to a method, in which the flow of feedstock containing ethylbenzene, passed through a molecular sieve membrane, and device for its implementation

The invention relates to a method for processing a stream of source material, including aromatic WITH8products, by allocating at least part of para-xylene with receiving stream depleted in para-xylene, which is then passed through a molecular sieve membrane, receiving the permeate enriched in para-xylene

The invention relates to a method of separation using membrane molecular sieve in the separation of hydrocarbons and/or oxygenated products

The invention relates to the petrochemical industry, for production of high-purity benzene, used in the petrochemical syntheses

The invention relates to a method for producing para-xylene from a boot containing a mixture of aromatic hydrocarbons containing 8 carbon atoms, which are circulating at least part of the load in the area to enrich the first fraction, at least 30 wt.% p-xylene and clean part of the above first fraction by one crystallization at high temperature T1, preferably in the range from +10 to -25C, at least one crystallization zone, isolated crystals in suspension in the mother solution, separating the crystals from the mother liquor, at least in the first separation zone, at the same time repeatedly suspension obtained crystals up to the required level in one area of re-suspending and partial melting

The invention relates to a method of purification of benzene from coke production and benzene obtained from fractions of pyrolysis oil from impurities saturated and unsaturated hydrocarbons, thiophene and carbon disulfide

The invention relates to the petrochemical industry, for the purification of benzene, obtained from a liquid hydrocarbon, C6-C7- fractions of pyrolysis oil from impurities unsaturated hydrocarbons

The invention relates to the petrochemical industry, for the purification of benzene, obtained from a liquid hydrocarbon, C6-C7- fractions of pyrolysis oil from impurities unsaturated hydrocarbons

The invention relates to organic synthesis, in particular it concerns a method for obtaining 2-[bis-(2-chloroethyl)amino] tetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide, monohydrate, known in the pharmaceutical industry as anticancer drug cyclophosphamide

The invention relates to medicine and relates to a new composition for treating or preventing prostate cancer, containing as the active ingredient N-[1-methyl-1-(4-methoxyphenyl)ethyl] -3-oxo-4-Aza-5-androst-1-ene-17-carboxamide, and method of treating or preventing prostate cancer using the composition

The invention relates to chemistry, in particular to pharmaceutical chemistry, and can be used for the production of anticancer drug

The invention relates to the field of medicine and pharmacology, and relates to pharmaceutical compositions for the prevention and treatment of tumors associated with human papilloma virus, namely dysplasia and cervical cancer and laryngeal papillomatosis

The invention relates to the derivatives of hintline formula I in which Z denotes-O-, -NH - or-S-; m = 1-5, integer, provided that when Z represents-NH-, m = 3 - 5; R1is hydrogen, C1-3alkoxy; R2is hydrogen; R3hydroxy, halogen, C1-3alkyl, C1-3-alkoxy, C1-3alkanoyloxy, trifluoromethyl or cyano; X1denotes-O-, -NR7, -NR8CO-, where R7and R8each is hydrogen, C1-3alkyl; R4choose one of the listed in paragraph 1 of the claims of the seven groups, except 4-(3,4,5-trimethoxyphenyl)-6,7-dimethoxyquinazoline, 4-(3-methoxybenzylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenoxy)-6,7-dimethoxyquinazolin and 4-(3,4,5-trimethoxyaniline)-6,7-dimethoxyquinazolin, or their salts
The invention relates to medicine, namely to oncourology, and can be used for the treatment of germ cell testicular cancer seminomas and neskromnoe histological patterns

The invention relates to the derivatives of dolastatin 15 General formula (I) a-b-D-E-F(G)r-(K)s-L, where a, b, D, E, F, G and K are remnants-amino acids and s and r are each independently 0 or 1

The invention relates to a new pyrimido[5,4-d]pyrimidines of General formula I and medicines with the properties of an inhibitor of protein tyrosine kinase receptors of epidermal growth factor on the basis of their

The invention relates to medicine and relates to the use of 1-hydroxy-4-cyclohexanedimethanol hydrochloride in clinical practice for the treatment of asthenic States, narcolepsy, warnings, and relieve mental and physical fatigue
Up!