RU2191601C1 - Medicinal preparation and method for treating erectile dysfunctions - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method deals with treating erectile DYSFUNCTIONS of different genesis and disorders of climacteric period. Medicinal preparation is based upon antibodies and contains activated formula of superlow doses of monoclonal, polyclonal or natural antibodies to endothelial nitrogen oxide synthetase obtained due to multiple successive dilution and external impact, predominantly by homeopathic technology. It is, also, suggested the method to treat erectile dysfunction by using activated forms of superlow doses of antibodies to endothelial NO-synthetase in the mixture of different, predominantly hundredth homeopathic dilutions. EFFECT: higher efficiency of therapy. 4 cl

Description

 The invention relates to medicine and can be used to treat erectile dysfunction of various origins and autonomic disorders of the menopause.

 The use of antibodies for the treatment of pathological syndromes is known from the prior art (SU 1131508 A, A 61 K 39/00, 1984; SU 1730144 A1, C 12 N 7/00, 1992).

 A known method of treating erectile dysfunction by regulating the content of cyclic guanosine monophosphate (cGMP) in the cavernous body during sexual stimulation (see the Register of medicines of Russia. Encyclopedia of drugs. 2001. M., 2000, S. 788-789). In this case, the relaxing effect of nitric oxide (NO) on the smooth muscles of the cavernous body is enhanced and blood flow in the penis is increased due to the introduction of a direct inhibitor of cGMP-specific phosphodiesterase type 5. However, the duration of the effect is limited to 3-5 hours, and the use used in the process the treatment (sildenafil citrate) is contraindicated in persons receiving nitric oxide donors or nitrates in any form.

 The invention is aimed at creating an effective tool and method for the treatment of erectile dysfunctions of various origins and autonomic disorders of the menopause.

 The solution to this problem is ensured by the fact that the drug contains an activated form of ultra-low doses of monoclonal, polyclonal or natural antibodies to endothelial synthetase of nitric oxide (NO synthetase), prepared by repeated serial dilution and external exposure mainly by homeopathic technology.

 In this case, to obtain antibodies using the whole molecule or polypeptide fragments of the enzyme endothelial NO synthetase.

 In addition, in the method of treating erectile dysfunctions and autonomic disorders of the menopause by regulating the content of cyclic guanosine monophosphate (cGMP) in the cavernous body during sexual stimulation, activated forms of ultra-low doses of antibodies to the whole molecule of endothelial NO synthetase or its polypeptide fragments obtained by repeated and external influences.

 It is preferable to use a mixture of various, mainly hundred, homeopathic dilutions of these antibodies.

 The drug obtained in accordance with the invention is a new pharmacological preparation that modifies the activity of the NO synthetase enzyme, as a result of which the synthesis of nitric oxide in the cavernous body during sexual stimulation increases, and blood flow in the penis increases.

 Moreover, in contrast to physiological (therapeutic) doses of antibodies, the activated forms of ultra-low doses of antibodies to NO synthetase do not bind (inactivate) the enzyme, but modify its effects. The new drug has a synergistic effect with the effect of NO synthetase. The presence of a therapeutic effect in ultra-low doses of antibodies activated by homeopathic technology, and even more so its unidirectionality with the action of the starting enzyme, does not follow from a known level of knowledge and has been identified by the author.

 The drug is prepared mainly as follows.

The solid-phase peptide synthesis method yields a synthetic polypeptide corresponding to a fragment of endothelial NO synthetase (type III) (1185-1205), with the following amino acid sequence:
Glu Arg Leu His Asp Ile Glu Ser Lys Gly Leu Gln Pro Thr Pro Met Thr Leu Val Phe.

 Glu Arg Leu His Asp Ile Glu Ser Lys Gly Leu Gln Pro Thr Pro Met Thr Leu Val Phe.

(Marsden PA, Schappert KT, Chen HS, Flowers M., Sundell CL, RA Wilcox JN,
Lamas S., Michel T. "Molecular cloning and characterization of human endothelial nitric oxide synthase." FEBS Lett. 307: 287-293, 1992).

The resulting peptide conjugated with methylated bovine serum albumin as a carrier is used as an immunogen in the immunization of rabbits. Monospecific serum to NO synthetase is obtained by immunization of rabbits with the indicated immunogen according to a well-known scheme (Vyazov OL, Laboratory Research Methods in Non-Infectious Immunology. M., Medicine, 1968 - 356 С.). Blood sampling is carried out from the marginal ear vein into sterile tubes. After retraction of the clot, the serum is separated by centrifugation, heated for 10 min at 56 ^o C to deactivate complement.

 The isolated antibodies to endothelial NO synthetase are repeatedly diluted sequentially and subjected to external mechanical action until ultra-small or small doses are obtained, for example, according to the homeopathic potentiation technology (see Homeopathic Medicines. Description and Production Manual, V. Schwabe, Moscow, 1967, p. . 12-38). In this case, a uniform decrease in concentration is made by successive dilution of 1 volume part of the starting substance (antibodies) in 9 volume parts (for decimal dilution D) or in 99 volume parts (for hundred dilution C) of a neutral solvent with multiple vertical shaking of each dilution obtained and using mainly separate containers for each subsequent dilution to obtain the desired dose (potency).

 External processing in the process of reducing the concentration can also be carried out by ultrasound, electromagnetic or other physical effects.

 A drug prepared in this way is used, mainly in dosage forms and dilutions accepted in homeopathic practice, in the form of alcohol or aqueous solutions or tablets (granules), obtained by soaking the filler in the dosage form by saturation with a potentized solution or by directly introducing the latter into a liquid dosage form .

 Example 1

 When studying the effect of activated forms of ultralow doses of antibodies to endothelial NO synthetase on the sexual behavior of sexually mature male rats under physiological inhibition of reproductive function, male rats aged 16 months weighing 600-700 g with an established degree of inhibition of sexual function were given oral potentiated antibodies to NO synthetase in a mixture of homeopathic dilutions C12 + C3O + C200 for 5 days, 1.5 ml per animal. After this, males were chased with females (age 4 months, weight 300 g), which are in the estrus stage of the reproductive cycle. For 15 min, copulative activity was recorded on the basis of the following parameters for each male: latent period of the cage (time between the first presentation of the female and the first cage), the number of courtships (sniffing, licking), the total number of cages, and the number of mating.

 It was found that after 5 injections of the drug, the number of courtship significantly increased (2 times) compared with the initial values in all animals; in 55.5% of the animals (with the initial average and marked sexual activity), the indicators of sexual activity significantly increased, which generally indicates a stimulating effect on the sexual activity of male rats under conditions of physiological inhibition of reproductive function.

 Example 2

 To study the effect of activated forms of ultra-low doses of antibodies to endothelial NO synthetase on the sexual behavior of sexually mature male rats under conditions of seasonal reproductive function suppression, male rats of 4 months old weighing 400-450 g were given orally potentiated polyclonal antibodies to NO synthetase in a mixture of homeopathic dilutions C12 + C3O + C200 for 5 days, 1.5 ml per animal. After this, males were chased with females (age 4 months, weight 300 g), which are in the estrus stage of the reproductive cycle. For 15 min, copulative activity was recorded on the basis of the following parameters for each male: latent period of the cage (time between the first presentation of the female and the first cage), the number of courtships (sniffing, licking), the total number of cages, and the number of mating.

 It was established that after 5 injections of the drug in animals of the experimental group, the latent period of cages significantly decreased, the number of courtship; at the same time, there was an increase in the total number of cages (2 times) and the number of mating (3 times) compared with the figures obtained from these same animals before the introduction of the drug. Thus, the introduction of the drug caused in male rats under conditions of seasonal inhibition of reproductive function an improvement in copulative activity, expressed in the need for repeated coitus in animals. The decrease in the number of courtship in this case is due to higher copulative activity.

 Example 3

 Patient S., 51 years old, turned to a urologist with complaints of decreased libido, erectile dysfunction, decreased satisfaction from sexual intercourse. These symptoms have been increasing over the past 2 years. In the last 3 years, she also noted periodic depression, tearfulness, memory and sleep disorders, decreased performance, heart attacks, fluctuations in blood pressure. Objectively: a moderate enlargement of the prostate gland was revealed. Diagnosis: erectile dysfunction on the background of involutional hormonal changes. Prescribed: a mixture of homeopathic dilutions of monoclonal antibodies to a fragment of human endothelial NO synthetase C12, C3O, C200, 1 tablet once every 3 days. 2 weeks after the start of treatment, the patient noted an improvement in erection and an increase in libido against the background of an improvement in general condition: overall tone increased, sleep improved. Recommended use of the drug 1-2 times a week. At a second appearance after 2 months after the start of treatment, he does not show previous complaints, notes the restoration of libido, erection and satisfaction from sexual intercourse.

 Example 4

 When studying the effect of activated forms of ultralow doses of antibodies to endothelial NO synthetase on the sexual behavior of sexually mature male rats under physiological inhibition of reproductive function, male rats aged 16 months weighing 600-700 g with an established degree of inhibition of sexual function were given oral potentiated antibodies to a whole molecule of endothelial NO synthetase (synthase) in a homeopathic dilution of C200 for 5 days, 1.5 ml per animal. In this case, the whole enzyme molecule was isolated from the endothelium of the bull’s aorta by the method described in the article by Bredt, D. S., & Snyder, S.H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad Sci. USA (1990), 87: 682-685).

 After this, males were chased with females (age 4 months, weight 300 g), which are in the estrus stage of the reproductive cycle. For 15 min, copulative activity was recorded on the basis of the following parameters for each male: latent period of the cage (time between the first presentation of the female and the first cage), the number of courtships (sniffing, licking), the total number of cages, and the number of mating.

 It was found that after 5 injections of the drug, the number of courtship significantly increased (2 times) compared with the initial values in all animals; in 55.5% of the animals (with the initial average and marked sexual activity), the indicators of sexual activity significantly increased, which generally indicates a stimulating effect on the sexual activity of male rats under conditions of physiological inhibition of reproductive function.

 Example 5

 To study the effect of activated forms of ultra-low doses of antibodies to endothelial NO synthetase on the sexual behavior of sexually mature male rats under conditions of seasonal reproductive function suppression, male rats of 4 months of age weighing 400-450 g were given orally potentiated natural antibodies to NO synthetase in a mixture of homeopathic dilutions C12 + C3O + C200 for 5 days, 1.5 ml per animal. Natural antibodies were isolated from the pool of sera of patients with hypertension. In the isolation, the method of affinity chromatography (immunosorption) was used on columns with synthetic endothelial NO synthase fragments adsorbed onto the solid phase (Sephadex) (according to the method described, for example, in the book Immunological Methods. Edited by G. Fremel. M., Medicine 1987, p. 427-432).

 After that, the males were sedimented with females (age 4 months, weight 300 g), which are in the estrus stage of the reproductive cycle. For 15 min, copulative activity was recorded on the basis of the following parameters for each male: latent period of the cage (time between the first presentation of the female and the first cage), the number of courtships (sniffing, licking), the total number of cages, and the number of mating.

 It was established that after 5 injections of the drug in animals of the experimental group, the latent period of cages significantly decreased, the number of courtship; at the same time, there was an increase in the total number of cages (2 times) and the number of mating (3 times) compared with the figures obtained from these same animals before the introduction of the drug. Thus, the introduction of the drug caused in male rats under conditions of seasonal inhibition of reproductive function an improvement in copulative activity, expressed in the need for repeated coitus in animals. The decrease in the number of courtship in this case is due to higher copulative activity.

Claims (4)

 1. A drug for the treatment of erectile dysfunctions, characterized in that it contains an activated form of ultra-low doses of monoclonal, polyclonal or natural antibodies to endothelial nitric oxide synthetase (NO synthetase), prepared by repeated serial dilution and external exposure mainly by homeopathic technology.  2. The drug according to claim 1, characterized in that for the production of antibodies using the whole molecule or polypeptide fragments of the enzyme NO synthetase.  3. A method for the treatment of erectile dysfunctions and autonomic disorders of the menopause by regulating the content of cyclic guanosine monophosphate (cGMP) in the cavernous body during sexual stimulation, characterized in that they use activated forms of ultra-low doses of antibodies to the whole molecule of endothelial NO synthetase or its polypeptide fragments, obtained by multiple serial dilution and external exposure.  4. The treatment method according to claim 3, characterized in that they use mixtures of various predominantly hundred-percent, homeopathic dilutions of antibodies to the whole molecule of endothelial NO synthetase or its polypeptide fragments.