Preparation for Treating Androgen Deficiency in Women

Abstract

A biologically active food additive, comprising drone brood homogenate in the daily amount of between 10 and 600 mg which can be combined with a calcium compound selected from calcium carbonate, calcium citrate, calcium gluconate, calcium aspartate, calcium amino acid chelate, calcium fumarate, calcium succinate, calcium ascorbate, calcium phosphate, or any combination thereof, the calcium compound content being from 16.67 to 93.75 wt. %; the content of drone brood being from 6.25 to 83.33 wt. %. Trials showed that administering the preparation contributes to the normalization of androgens in women resulting in the overall health improvement and disappearance or decrease of clinical signs of androgen deficiency, as well as sustaining the normal testosterone level, compensating for the deficit of calcium in the body, facilitating more efficient assimilation of calcium and retention thereof in the bony tissue for a long time.

Claims

1. A preparation for treating androgen deficiency in women comprising a drone brood homogenate in the amount of from 10 mg to 600 mg.

2. The preparation as claimed in claim 1, further comprising a pharmacologically active calcium compound chosen from a series comprising calcium carbonate, calcium citrate, calcium gluconate, calcium aspartate, calcium amino acid chelate, calcium fumarate, calcium succinate, calcium ascorbate, calcium phosphate, or any combination thereof, and wherein the calcium compound is in the amount of 16.67-93.75 weight % and the drone brood is in the amount of 6.25-83.33 weight %.

3. The preparation according to claim 1, wherein said preparation is made in a tablet, capsule or powder form.

4. The preparation according to claim 2, wherein said preparation is made in a tablet, capsule or powder form.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0022] The use of drone brood in the present invention can be explained by the following. The drone brood is a donor of sex entomological hormones such as prolactin, estradiol, progesterone, testosterone, which stimulate the reproductive functions in men and women. Rich in hormones and vitamins not being hormone substitutes, the drone brood is effective against the hormonal background disorders, stimulates the central mechanisms for regulating the rate of androgen formation and excludes possible SET. The studies conducted in the Apiculture Scientific-Research Institute (Rybnoye, Ryazan region, Russia) demonstrated the safe use of the drone brood and also proved the gonadotropic effect of the drone brood on the stimulation of central links controlling the testosterone synthesis. (Krivtsov N. I. et al., Theory and Methods of Apitherapy, Moscow, 2007). Therefore, the testosterone level in the body may be sustained using the drone brood.

[0023] The impact of drone brood upon the male body has been studied substantially well. It is the stimulation of the function of the testicles to produce testosterone that explained that impact. With that in view, the use of drone brood to stimulate producing testosterone in women, especially in postmenopausal age, was not believed to be obvious considering that it was not clear which body organ should be stimulated to produce testosterone in women. It has been known that androgens are produced in women either by suprarenal cortex or by ovaries. But with regard to women in the postmenopausal age, the latter way of the synthesis of testosterone falls down because of the general decline of the functions of this organ. As to the former way of synthesizing androgens, the adrenal glands synthesize androstenedione, dehydroepiandrosterone and 1143-hydroxyandrostenedione. These hormones are known to be precursors of testosterone. The authors of the present invention have put forward an assumption that it is the liver that promotes producing testosterone in women breaking the entomological testosterone down to human testosterone (Phylippovich Yu. B., Physiological fundamentals of human life and activities. Moscow, Vlados, 2005, p.336). But no matter what the way of synthesizing testosterone in women is, it does not seem possible to be drawing parallels with the ways of synthesizing this hormone in men.

[0024] It has been known, for example, that all steroids are compounds of a lipid nature. They are poorly soluble in water, that is why in blood they are in bound state with blood plasma proteins, with only insignificant portion thereof being free. It is just the free steroids that are highly active biologically: they cross membranes of target cells. Cholesterol is a precursor of steroids, and it turns into progesterone in suprarenal cortex cells. Progesterone in turn can evolve into corticosteroids, androgens and estrogens (Lyubimova Z. V., Age specific physiology, part 1, Moscow, Vlados, 2004, p. 105).

[0025] One of dietary advices to raise the level of testosterone in men is to increase the amount of the cholesterol consumed. For women, however, this recommendation cannot take place because it can entail an increase of estrogens or corticosteroids. It has been known that endocrine glands in men and women, when identically stimulated, behave differently in synthesizing hormones. For example, releasing follitropin by hypophysis results in producing estrogens in women and testosterone in men (Hurovetz G. V., Age specific anatomy and physiology, Moscow, Vlados, 2013, p. 215). Thus, even though drone brood has been known to act in men as an activator of producing their own testosterone, it was not to be expected, with differences in functioning of the endocrine systems in men and women in view, that the matters influencing the central components responsible for synthesizing testosterone in men will behave similarly in women. Even more so, it is not to be expected that the matters regulating production of testosterone in testicles will influence the testosterone production in women.

[0026] The present invention is based on an unexpected discovery of the fact that drone brood shows androgenotropic effect in women. The technical result of the invention is the increasing in blood in women of the level of their own androgens, particularly testosterone.

[0027] Previously, it was uncovered by the inventors that drone brood was a donor of various sex hormones (estradiol, progesterone, testosterone) in men and women (RU2498811, Nov. 20, 2013; RU2412616, Feb. 27, 2011; RU2497533, Nov. 10, 2013). At that time, however, it was not known yet which of those hormones are donated by drone brood in women. Not disclosed in those publications is the information that administering drone brood to women will result in raising the level of testosterone in their blood. From what was known, it was logical to deduce that it will be the level of estradiol or progesterone that will raise in women. Various sources inform about a pronounced gonadotropic action of drone brood, which stimulates the activity of the sex glands. It has been known that the drone brood homogenate appears to be a stimulator of the central mechanisms regulating the production of the male sex hormones (androgens), restores biochemical characteristics of male gonads (the concentration of testosterone in blood and of fructose in the spermatocyst liquid), prostate, as well as sperm production. In men, the use of drone brood is effective in sex dysfunction and infertility and enhances libido. In women, taking drone brood homogenate stimulates the function of ovaries and enables restoring the endocrine profile and reproductive performance. In other words, it has been known from a number of publications that the drone brood homogenate stimulates production of androgens in men and of estrogens in women.

[0028] Those publications relate to treating osteoporosis. It has been known that osteoporosis in women can have estradiol-related nature. Summing up the above, the inventors believe that prior art discloses no solution that results in achieving the above-stated technical resultthe increasing in blood in women of the level of their own androgens, particularly testosteroneupon using biologically active supplements, in particular drone brood. With that, it was found that the operation of entomological testosterone differs substantially from that of exogenous testosterone, such as testosterone propionate, which when used becomes very harmful to woman's health resulting in masculinization, acne, voice coarseness, hypertrichosis, baldness, clitoromegaly, thrombophlebitis. Considering that the liver breaks testosterone propionate down to estrogens, it would be illogical to expect that entomological testosterone of drone brood will be broken down in the liver to human testosterone.

[0029] The authors of the present invention developed a preparation based on drone brood homogenate to be made in a tablet, capsule or powder form. The homogenate can be combined with a calcium compound including a pharmacologically active calcium compound chosen from a series comprising calcium carbonate, calcium citrate, calcium gluconate, calcium aspartate, calcium amino acid chelate, calcium fumarate, calcium succinate, calcium ascorbate, calcium phosphate, or any combination thereof. In this preparation, the calcium compound is in the amount of 16.67-93.75 weight % and the drone brood is in the amount of 6.25-83.33 weight %.

[0030] Also, a trial was performed to explore how this preparation acts upon hormonal state of women having androgen deficiency. Since 2009 to March of 2013, 72 women in the age range of 49-85 were examined. Only women with androgen deficiency confirmed hormonally and clinically were included in the trial. The trial included a physical examination, a general laboratory examination, as well as a hormonal examinationestimation of testosterone and sex hormone-binding globulin (SHBG). The IMMULITE 2000 Immunoassay System was employed for the hormonal examination with the use of an immunochemiluminometric assay. All the women were divided into two groups comparable in terms of age and severity of the disease. The first group, 38 women, had been taking the claimed preparation orally, one tablet (100 mg of drone brood in a tablet) in the morning and for the night, for three months, thrice a year. The second, control group (34 women) had been taking placebo under the same regimen.

[0031] A statistical review of the data obtained was undertaken using the StatSoft, Windows XP software package. Quantitative characters were described by mean and mean root square deviations. The results were presented in the Mm format, where M is an arithmetic average and man error in mean. Differences were considered statistical ones where significance value p<0.05. Noted after the termination of the course of treatment were mood improvement, increment in activity, increase of muscle power, decrease of dysuric symptoms, decrease of osteoporosis activity. None of that was noted in the women of the second group. The hormonal examination showed that before the treatment the general testosterone concentration in women was 1.10.4 nmole/1 for the first group and 1.20.5 nmole/1 for the second group (p>0.05), the reference concentration for this method being 1.7-3.4 nmole/1. The SHBG concentration in the first and second groups before the treatment were 64.32.6 nmole/1 and 62.82.9 nmole/1 (p>0.05), respectively.

[0032] 29 out of 37 patients noted amelioration of signs after 9 months of the treatment with the claimed preparation. When assessed, the lab values showed the increasing of general testosterone concentration in blood plasm from 1.10.4 nmole/1 to 2.50.6 nmole/1 (p<0.05), the SHBG concentration from 64.32.6 nmole/1 to 115.05.9 nmole/1 (p<0.05). In the second group taking placebo, no patient showed any positive shift in testosterone content and HSBG increase.

[0033] The results of the conducted trial make it clear that administering the claimed preparation contributes to the normalization of androgens in women resulting in the overall health improvement and disappearance or decrease of clinical signs of androgen deficiency. The effect can be reached at when the daily dosage of the preparation is between 10 and 600 mg. The obtained data demonstrate that aging comes with the decrease of the hormonal androgen status that brings about androgen deficiency symptoms onset.

[0034] Regarding osteoporosis, although the components forming part of the inventive biologically active food additive are known in the folk or traditional medicine, their combination in one product to treat osteoporosis is not disclosed in the prior art.

[0035] The combined use of the above-mentioned components enables a more efficient assimilation of calcium by the body since calcium not only enters the body but is also retained in the bony tissue thanks to the drone brood. It has been found that the drone brood is able to improve the assimilability of calcium by the body and to retain the same in the bony tissue for a long time, i.e. to ensure a prolonged effect of the bony tissue calcium intake. In addition, the administration of calcium together with the drone brood makes it possible to lower the dosage of the calcium compounds, to thus prevent lithogenesis in the kidneys as well as other negative effects of taking the calcium preparations (for example, gastroenteric upsets) from occurring.

[0036] The ratio of the calcium compound and the drone brood varies within a wide range. The range width is determined by the individual parameters: age, gender, state of health and other factors.

[0037] It is known that the upper acceptance limit for the administration of calcium is 1000-1500 mg per day. Due to the combined administration of the drone brood and the calcium compound, the daily dosage of calcium may be lowered since the bioavailability (assimilability) of calcium is improved and bone resorption (calcium depletion) is prevented.

[0038] Based on the foregoing, the maximum consumption of calcium is suggested to be 600 mg.

[0039] The minimum consumption of calcium is determined by the minimum body need for ionized calcium, that being of 200 mg.

[0040] The maximum consumption of the drone brood to prevent osteoporosis is determined by the expediency of use and is 1000 mg.

[0041] The minimum consumption of the drone brood to prevent osteoporosis is 40 mg (see RU2233666 C1, Oct. 8, 2004) and is determined by the pharmacological activity.

[0042] Consequently, the administration range of the components forming the biologically active food additive according to the present invention is as follows: drone brood: 40 to 1000 mg or 6.25% to 83.33%; calcium: 200 to 600 mg or 16.67% to 93.75%.

[0043] Therefore, the combined use of the drone brood and calcium compound in the additive makes it possible to reduce significantly the maximum (upper) daily consumption of calcium from 1500 mg to 600 mg thereby reducing the negative side effects of calcium on the human body and widening the group of persons able to use calcium preparations. The reduction in the maximum daily consumption of calcium is necessary because an opposite disease, hypercalcemia, quite often occurs in cases where calcium preparations are administered in the doses of 1000 to 1500 mg. For example, of the 1000 patients continuously receiving preparations against osteoporosis, 86 had hypermineralization of the 1 to 3 degree (Strukov V. I., Actual Problems of Osteoporosis, Penza, 2009, Rostra Publishers).

[0044] The above-identified quantitative ratio makes it possible to ensure an optimum ingress of calcium for each individual and its most complete assimilation thanks to the claimed amount of the drone brood, which ensures a certain content of sulfhydryl enzyme groups in the additive, as well as testosterone, progesterone, prolactin and estradiol. The drone brood is rich in amino acids. The amino acids in turn act as transporters of calcium to the cell (Strukov V. I., Ibid.). In order for calcium to be assimilated, vitamins A, C, E, D and micronutrient elements, such as magnesium, copper, zinc, phosphorus are also required. All of them are present in the drone brood.

[0045] As a result, all calcium being administered is completely assimilated by the bony tissue. Surprisingly, it has been found that the retention of calcium in the bony tissue for a prolonged time is provided by sulfhydryl enzyme groups in the drone brood, vitamins D and E, so that the process of its depletion slows down. Besides, a long period of the normal bony tissue density is accounted for by a sufficiently high content of phosphorus in the drone brood which enters the body in the amount specified above, thereby facilitating the assimilation of calcium.

[0046] Therefore, the problem of not only saturating the bony tissue with calcium but also of retaining the same for a long time therein has been solved for the first time by means of the combined use of the calcium preparations and the drone brood in the claimed ratio. The risk of fractures has been considerably lessened as compared to the prior art preparations since a 5% increase in the mineral bone density leads to a 35% reduction in the risk of fracture, and the additional antiresorptive feature of the claimed preparation reduces the risk of fracture by another 20%.

[0047] In order to prepare the biologically active food additive in accordance with the present invention, there is provided a powdered calcium compound selected from calcium carbonate, calcium citrate, calcium gluconate, calcium aspartate, calcium phosphate, calcium citrate at a concentration of 16.67 wt. % to 93.75 wt. % and is mixed with a drone brood at a concentration of 6.25 wt. % to 83.33 wt. % until a homogeneous mixture is formed. The resulting mixture is then tableted or capsulated. The biologically active food additive presents a homogeneous light beige powder with a humidity of 1 to 3.5%, which is further subjected to tableting or capsulation. A tablet or a capsule contains 1 g of the mixture.

[0048] When preparing the biologically active food additive, the drone brood is used in the form of a lyophilizate. In order to obtain a lyophilizate, the larval drone brood is homogenized using a mixer. The homogenate comprises a thick yellow creamy liquid with a characteristic odor. The content of dry matter in the homogenate does not exceed 22.5%. The lyophilizate is obtained by freezing the homogenate for 2-3 hours at a temperature of minus 35-40 C. followed by vacuum sublimation at a residual pressure of 0.1-0.6 mm hg for 40-48 hours and bringing the temperature to 25-30 C. by the end of lyophilization. The lyophilizate includes a powder whose color varies from beige to yellow, with a high hygroscopicity and residual moisture content of 1-3.5%. In other words, the preparation conditions of lyophilizate allow for preserving the solid matter composition of the drone brood homogenate without changes except for the moisture content.

[0049] Provided below are the examples of preparing the biologically active food additive.

Example 1

[0050] 17 kg of powdered calcium gluconate was provided and mixed with 83 kg of the drone brood lyophilizate. The mixture was then stirred to homogeneity and the resulting product was capsulated.

Example 2

[0051] 90 kg of powdered calcium carbonate was provided and mixed with 10 kg of the drone brood lyophilizate. The mixture was stirred to homogeneity and then tableted.

[0052] For prevention of osteoporosis, one capsule of the biologically active food additive is administered 3 times a day for one month separately from meals. A one-month break in the administration should be provided. The serum calcium value does not decrease during this period, meaning that the calcium content is sustained at a normal level.

[0053] The above technical effect is demonstrated by way of the following examples.

Example 1

[0054] A human subject, female, born in 1959. The mineral bone density of T 1.4 was measured in the distal antibrachium by means of densitometer DXT-200 of Osteometer MediTech, Inc. Osteopenia was diagnosed, and 1 g of calcium gluconate was administered 3 times a day. A six-month course of preventive medication was conducted. A re-evaluation six months later showed a reduced bone density down to T 1.6. That is, the mineral bone density (MBD) decreased. After a one-month break in the administration, the serum calcium value was below the normal value.

For reference: MBD normal valuethe values of T criterion with a standard deviation of +1 to 1 from the peak bone mass;
1.sup.st degree osteopeniaMBD from 1 to 1.5;
2.sup.nd degree osteopeniaMBD from 1.5 to 2;
3.sup.rd degree osteopeniaMBD from 2 to 2.5;
1.sup.st degree osteoporosisMBD from 2.5 and less without fractures;
2.sup.nd degree osteoporosisMBD from 2.5 and less with osteoporotic bone fractures.

[0055] The densitometric T scale presents the number of standard deviations up and down an average bone mass value. The T criterion decreases in parallel with a gradual reduction in the bone mass with age and is used to evaluate the MBD in adults.

Example 2

[0056] The same female human subject with diagnosed osteopenia and the mineral bone density of T 1.6 was administered one capsule of the claimed biologically active food additive 3 times a day. A six-month preventive medication course was conducted following the pattern of one-month administration/one-month break. The mineral bone density increased to T 1.2. The serum calcium value normalized. No reduction in the serum calcium value was observed during the re-examination performed three months later.

[0057] Therefore, apart from sustaining the normal testosterone level and compensating for the deficit of calcium in the body, the inventive biologically active food additive according to the present invention also facilitates a more efficient assimilation of calcium and retention thereof in the bony tissue for a long time (i.e. has a prolonged activity) and thus is believed to be an excellent preparation for the prevention of osteoporosis.