RU2728709C1 - Reproductive function enhancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: present invention relates to medicine, specifically to an agent for increasing reproductive function, comprising an active portion of chemical origin and a target additive, characterized in that as an active portion it contains an aqueous solution of formaldehyde 36.5–37.5 % concentration, and the target additive is an isotonic solution of sodium chloride for injections of 0.85–0.95 % concentration, with the following ratio of components, pts.wt.: aqueous solution of formaldehyde 36.5–37.5 % 1.5–1.8; isotonic solution of sodium chloride for injections 0.85–0.95 % 998.2–998.5.

EFFECT: present invention provides preparing an effective preparation providing high Apgar scores of 8 to higher.

1 cl, 19 ex

Description

The invention relates to medicine, namely to andrology, and can be used to increase the reproductive function of men and women. In addition, it can be used in veterinary medicine for the treatment of mammals with impaired fertility.

Currently, male and female infertility is a constant concern for humanity. However, the question of procreation is a highly intimate matter. Therefore, more or less accurate accounting of the prevalence of primary and secondary infertility is not easy.

Primary infertility is considered to be the inability for two permanent partners to give birth to their first child, provided they have regular sex life for 3-5 years without using contraceptives.

Secondary infertility occurs in partners who have already become parents, but are faced with the problem of the inability to increase their family.

In Russia, official rates of infertility are similar to global figures. This is about 5% of families. However, not all couples go to special centers for infertility problems. It is believed that the real prevalence of infertility can reach 20%.

In the absence of a married couple of children, a man, a woman, or both partners at the same time may be “to blame”.

A known agent for increasing male reproductive function (see RF patent No. 2665636 according to class IPC A61K 31/197, publ. 09/03/2018), containing carnitine tartrate, zinc sulfate, alpha-tocopherol acetate, folic acid, sodium selenite and excipients ... The tool provides an improvement in the functional state of the organs of the male reproductive system with an additional effect of harmonizing organoleptic perception.

However, the agent is a biologically active food supplement, and despite the fact that it contains substances that have a beneficial effect on the male reproductive system, the sachet contains a lot of sugar (70% of the total mass of substances) and is clearly contraindicated for people with pancreatic diseases. It should also be noted that multicomponent mixtures should be used with caution by people prone to allergic reactions.

The above tool uses a chemical compound of selenium, which is known for its toxicity, which prevents its use in sufficient doses to achieve the result.

There is a known agent for improving reproductive function in women (see RF patent No. 2616521 according to class IPC A61K31 / 198, publ. 17.04.17), containing L-Arginine, magnesium citrate, ascorbic acid, sacred vitex extract containing aucubin, zinc citrate , tocopherol acetate, pyridoxine hydrochloride, riboflavin, folic acid, potassium iodate, sodium selenite and excipients (sugar powder, Amorphous silicon dioxide E551, Natural cranberry flavor, Stevia extract, E120 dye (carminic acid content) 50%), etc. This remedy for improving the condition of the reproductive system can be used in men.

The tool is taken once a day with meals, dissolving the contents of the sachet bag in 200-300 ml of water. The course is carried out within one month, if necessary, the course is repeated.

However, the product is multi-component and can pose a real threat to the life of people suffering from allergic diseases. For example, the dye E120 (Carmine), which is part of the drug - even with moderate consumption, can harm allergy sufferers and people with individual intolerance to carmine. At the moment, it is reliably known about several cases of anaphylactic shock that occurred after eating food containing Carmine dye. The drug also contains a lot of sugar (more than 50%), which indicates the impossibility of its use for people prone to diabetes. Stevia, which is also part of the drug, can interact with antifungal and anti-inflammatory drugs, antimicrobial and antiviral drugs, appetite suppressants, drugs that lower cholesterol, and many others to reduce their therapeutic effect.

In addition, fragrances with prolonged use (and the drug must be taken for at least a month) can cause, in particular, impaired liver function.

Known means of stimulating reproductive behavior and the efficiency of reproduction and productivity of sows (see RF patent No. 2684717 on class IPC A61K31 / 568, publ. 11.04.2019), containing 0.0004% steroid hormone and 0.0004% quinoline.

However, it should be noted that taking steroid drugs at a young age leads to destabilization of the endocrine system, which is in the period of its rise and formation. In addition, this remedy does not cure disorders in the reproductive system, but only stimulates sexual desire.

A known means of increasing reproductive function in rats (see RF patent No. 2564016 according to class IPC A61K31 / 4184, publ. 27.09.2015), containing potassium salt 2- [1- (1,1-dioxothietanyl-3) benzimidazolyl-2- thio] acetic acid (formerly known as an immunotropic and anxiolytic agent). The agent shortens the estrus phase and increases the proestrus phase of the ovulatory cycle, increases the pregnancy index and fertility of experienced female rats, and also reduces embryonic fetal death.

However, the effect of the potassium salt of acetic acid on the human body has not been fully studied and can be dangerous for people with diseases of the kidneys, heart, blood vessels, urinary tract, and gastrointestinal tract.

Known means for correcting reproductive function in cows (see RF patent No. 2634055 according to class IPC A01K67 / 00, publ. 23.10.2017), which is used as an immunostimulator metallosuccinate, which is administered at a dose of 2.0 ml / 100 kg of live weight per 10, 11, 12 days after calving. The use of the product allows you to correct the nonspecific immunity of cows by activating metabolic reactions in the body.

However, metal succinate is a multicomponent mixture (ASD F-No.2 - 4.0; succinic acid - 1.0; iron sulfate - 0.2; copper sulfate - 0.01; zinc sulfate - 0.01; cobalt sulfate - 0 , 1; novocaine - 0.25; polyethylene glycol - 3.0), which in turn can be dangerous for people prone to allergies. In addition, the drug contains polyethylene glycol - a strong allergen, after using which, for a long time, one should not be exposed to sunlight in order to avoid skin diseases (including cancer). Polyethylene glycol has also been proven to be an endocrine disruptor.

Closest to the claimed is a means for increasing reproductive function (see RF patent No. 2487705 according to class IPC A61K31 / 095, publ. 20.07.2013), containing a clathrate complex of β-cyclodextrin with 9-phenyl-sym-octahydroselenoxanthene in α-crystalline form, and corresponding to the structural formula

However, treatment with this drug is long enough (at least 10 weeks), which creates conditions for a violation of the course. In addition, the study was conducted only on rats, which does not guarantee similar results in humans.

The technical problem of the claimed invention is to expand the scope of drugs used to improve reproductive function, reduce embryonic fetal death and increase the viability of newborns.

The technical result is the development of an effective drug that provides high rates of assessment of the newborn on the Apgar scale from 8 points and above.

The technical result is achieved in that the agent for enhancing reproductive function, containing an active part of chemical origin and a target additive, according to the invention, contains as an active part an aqueous solution of formic aldehyde of 36.5-37.5% concentration, and as a target additive - isotonic sodium chloride solution for injection 0.85-0.95% concentration with the following ratio of components, wt. %:

aqueous solution of formic aldehyde 36.5-37.5% 0.05-0.07 isotonic sodium chloride solution for injection 0.85-0.95% rest

The introduction of formic aldehyde (formic acid aldehyde) at a low concentration helps to improve reproductive function, as well as its restoration with age-related extinction. In our opinion, this is due to the effect on the synthesis of hormones by the hypothalamus. One of the most important hypothalamic hormones is gonadoliberin. It is a peptide hormone of the hypothalamus, a follicle-stimulating and luteinizing hormone releasing factor. Consists of 10 amino acid residues. It is formed in the hypothalamus from a high molecular weight precursor and transported to the pituitary gland, where it stimulates the secretion of follicle-stimulating and luteinizing hormones, which regulate the secretion of sex steroids. Regulates reproductive function, stimulates spermatogenesis in males and maturation of follicles in females, induces ovulation, and affects sexual behavior.

Formic aldehyde is a physiological substance with high biological activity, capable of modifying (methylating and demethylating) both nucleotides and amino acids. It can be assumed that its short-term effect on the hypothalamus causes the effect of prolonged release of gonadotropins, leading to the resumption of ovulation.

The half-life of formic aldehyde in the blood is about 1 min (see, Shindyapina A.V. Molecular biological bases of the control of endogenous methanol and formaldehyde in mammals: dissertation of the candidate of biological sciences / Moscow, 2017. - 123 p .; Malyutina N N., Taranenko L. A. Pathophysiological and clinical aspects of the impact of methanol and formaldehyde on the human body // Modern problems of science and education. - 2014. - No. 2.)

At this time, the concentration of formic aldehyde is likely to increase in the cells of all organs, including the endocrine glands, since the metabolism of any cell is accompanied by the formation of formic aldehyde (see, Shindyapina A.V. Molecular biological basis for the control of endogenous methanol and formaldehyde in mammals : Candidate of Science thesis / Moscow, 2017 .-- 123 p.) With the intramuscular injection of small amounts of formic aldehyde, its concentration in the blood returns to the physiological norm after a few minutes. Therefore, we can talk about the effect of formic aldehyde on the hypothalamus, which, presumably, contributes to the prolongation of the release of gonadotropins.

Thus, the unknown use of an injectable drug to increase reproductive function, which allows to regulate the synthesis of gonadoliberin, a peptide hormone of the hypothalamus that stimulates the secretion of follicle-stimulating and luteinizing hormones through the use of a mixture of an aqueous solution of formic aldehyde of a certain concentration with isotonic sodium chloride solution, allows us to conclude that there is an "inventive" "in the claimed invention.

An aqueous solution of formic aldehyde is a clear, colorless liquid with a peculiar pungent odor, miscible with water and alcohol in all ratios.

Formic aldehyde (formic acid aldehyde) is a representative of the NSOH aldehyde class. It is a colorless gas with a pungent odor, molecular weight 30.03, its density at 20 ° C is 0.815, melting point 92 ° C, boiling point 19.2 ° C. Let's well dissolve in water, alcohol.

Isotonic sodium chloride solution for injection is a colorless transparent liquid with a salty taste. The solution is sterile, pyrogen-free. Produced in a concentration of 0.85-0.95%.

The inventive agent is a clear, colorless, odorless liquid, slightly salty taste.

An agent for enhancing reproductive function is prepared as follows.

Take 1.5-1.8 weight parts of a 36.5-37.5% medical solution of formic aldehyde, add it to 998.2-998.5 weight parts of a sterile 0.85-0.95% chloride solution sodium for injection to obtain a 0.05-0.07% solution of formic aldehyde. The product is stored in a dark place at a temperature of 15-35 ° C.

Example 1. Take 0.18 ml of a 37% medical solution of formic aldehyde, add it to 99.82 ml of sterile 0.9% isotonic sodium chloride solution. The mixture of solutions is thoroughly mixed. The final concentration of formic aldehyde in the resulting product will be 0.066 wt%.

Example 2. Take 0.15 ml of a 37% medical solution of formic aldehyde, add it to 99.85 ml of sterile 0.9% isotonic sodium chloride solution. The mixture of solutions is thoroughly mixed. The final concentration of formic aldehyde in the resulting product will be 0.055 wt%.

Example 3. Take 0.18 ml of 37.5% medical solution of formic aldehyde, add it to 99.82 ml of sterile 0.95% isotonic sodium chloride solution. The mixture of solutions is thoroughly mixed. The final concentration of formic aldehyde in the resulting product will be 0.067 wt. %.

For men and women, the drug is administered intramuscularly at a dose of 4-6 ml. The minimum frequency of administration is 7 injections, which are administered on the 7th, 21st, 30th, 60th, 80th and 100th day after the first injection.

For animals, in particular for cows, the agent is also administered intramuscularly in a dose of 6 ml at intervals on the 7th and 14th day after the first injection.

Example 4.

Patient M., 35 years old. Diagnosis - aspermia after radiation exposure.

The course of treatment was carried out - 10 injections within 8 months.

After the second injection, immobile sperm appeared in the semen.

After the fifth injection, 35% of the sperm were motile. After the last injection, 50% of the sperm were motile.

Example 5.

Patient S., 23 years old. Diagnosis - violation of the menstrual cycle (dysmenorrhea).

The course of treatment was carried out - 7 injections within 6 months.

As a result of the treatment, the menstrual cycle became regular (observation for 3 years).

Example 6.

Patient K., 27 years old. Diagnosis - violation of the menstrual cycle (aminorrhea)

The course of treatment was carried out - 14 injections within 12 months.

As a result of the treatment, the menstrual cycle was restored and became regular (follow-up for 5 years).

Example 7.

Patient V., 30 years old. Diagnosis - low hemoglobin levels (75-80 g / l), high ESR (40-50 mm / h), increased creatinine (110-120 μmol / l).

The course of treatment was carried out for 2.5 years.

After the treatment, all indicators returned to normal. A healthy child was born, which was assessed by the doctor at 9 points on the Apgar scale.

Example 8.

Patient J., 38 years old. Diagnosis - there are secondary male sexual characteristics (profuse body and face hair growth). Infertility.

The course of treatment was carried out - 7 injections within 100 days.

As a result of the treatment, excessive hair loss disappeared, a healthy child was born, which was assessed by the doctor at 9.5 points on the Apgar scale (observation for 16 years).

Example 9.

Patient K., 24 years old. Diagnosis - multiple cysts of the right ovary.

The course of treatment was carried out - 7 injections within 6 months.

The patient recovered completely.

Example 10.

Patient Z., 40 years old. Diagnosis - multiple cysts of the right and left ovary.

The course of treatment was carried out - 14 injections within 12 months.

The patient recovered completely.

Example 11

Patient G., 36 years old. The diagnosis is endometriosis.

The course of treatment was carried out - 10 injections within 8 months.

The patient recovered completely.

Example 12.

Sick wife D., 34 and 39 years old. The diagnosis is infertility of unknown etiology.

A course of treatment was carried out - 7 injections for 100 days for each of the spouses.

The treatment resulted in pregnancy, which ended in the birth of a girl, who was rated by the doctor at 10 points on the Apgar scale. The baby girl was monitored for a year. The development is normal, the child is healthy.

Example 13.

Patient Y., 39 years old. Diagnosis - early miscarriage (twice).

A course of treatment was carried out - 7 injections for 100 days for each of the spouses.

The treatment resulted in pregnancy, which ended in the birth of a boy, who was assessed by the doctor at 8.5 points on the Apgar scale. The development is normal, the child is healthy. The observation period is two years.

Example 14.

Patient Sh., 37 years old. Diagnosis - obstruction of the fallopian tubes, infertility. Two failed IVFs.

The course of treatment was carried out - 7 injections within 100 days.

The treatment resulted in pregnancy with IVF, which ended in the birth of a boy, who was rated by the doctor at 9 points on the Apgar scale. The child is healthy. The observation period is one year.

Example 15.

Patient V., 58 years old. Diagnosis - early menopause (came at 40).

The course of treatment was carried out - 7 injections within 100 days.

As a result of the treatment, the menstrual cycle was restored and became regular (observation for 3 years).

Example 16.

Patient N., 65 years old. Diagnosis - menopause (came at 50).

The course of treatment was carried out - 7 injections within 100 days.

As a result of the treatment, the menstrual cycle was restored and became regular (observation for 2 years).

Example 17.

Patient O., 71 years old. Diagnosis - menopause (came at 55).

The course of treatment was carried out - 7 injections within 100 days.

As a result of the treatment, the menstrual cycle was restored and became regular (observation for 1 year).

Example 18.

Farm No. 1 processed fifteen heads of cattle, which were transferred to the fattening group for further culling due to low milk productivity and barrenness (they did not fertilize for two years).

The course of treatment was carried out, consisting of two blocks (the interval between blocks is 60 days), three injections at intervals of 7 days.

As a result of the treatment, all cows were fertilized and calved over the next year. The calves were born healthy.

Example 19.

In farm No. 2, a study was carried out on four groups of cows-analogues according to age in lactation, level of milk production, live weight, origin, physiological state. Each group had 10 goals. All cows were kept together under the same conditions.

Intramuscular injections of the drug were made three times at intervals of 7 days. 1st group at a dose of 4 ml, 2nd group - 6 ml, 3rd group - 8 ml. 4th group was the control.

During the research, the following indicators of the reproductive function of cows were studied: the course of labor, the postpartum period, the manifestation of postpartum complications, the duration of the period of fruitful insemination, the number of inseminated animals.

As a result of the conducted studies, it was found that the reproductive function of highly productive cows depends on the dose of the drug.

Thus, the best results were obtained using 6 ml of the preparation as a single dose for administration. All cows were fertilized and calved within the next year. The calves were born healthy.

The given data show that the agent improves the reproductive functions of the human and animal organism, leads to an increase in the viability of newborns, providing high criteria for assessing newborns on the Apgar scale from 8 points and above, namely, the color of the skin, heart rate, reflex excitability, muscle tone, breathing.

Claims (2)

An agent for enhancing reproductive function, containing an active part of chemical origin and a target additive, characterized in that it contains an aqueous solution of formic aldehyde of 36.5-37.5% concentration as an active part, and isotonic sodium solution as a target additive chloride for injection 0.85-0.95% concentration with the following ratio of components, parts by weight: aqueous solution of formic aldehyde 36.5-37.5% 1.5-1.8 isotonic sodium chloride solution for injection 0.85-0.95% 998.2-998.5