RU2324372C2 - Selective inhibition of estrogen production and activity in human - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: bioactive food additive contains the products of Morinda citrifolia processing, which is used to inhibit the aromatase or aromatase enzymes transforming the androgens to estrogens, to inhibit the receptor binding to estrogens and to decrease and/or regulate the estrogen production. The invention reduces and regulates the estrogen production.

EFFECT: efficient in treatment of estrogen-dependent cancer and conversion of estrogen-dependent malignant tumors.

60 cl, 1 tbl, 1 ex

Description

FIELD OF THE INVENTION

The present invention relates to estrogenic action in the human body. More specifically, the present invention relates to the use of a biologically active composition or additive for selectively inhibiting estrogen production and providing estrogenic effects in the human body, where the composition includes one or more processed products of an Indian mulberry plant, the scientific name of which is Morinda citrifolia L.

BACKGROUND

Estrogens are steroid hormones that are primarily produced by the ovaries and are responsible for stimulating estrus, as well as for the development and maintenance of female secondary sexual characteristics. In humans, estrogen is produced in the ovary, probably in the cortex of the adrenal glands in the testes and the fetal-placenta complex. Estrogens have various functions. For example, they are responsible for the development of female secondary sexual characteristics, and during the menstrual cycle, their effect on the female genitalia is to provide an environment suitable for fertilization, implantation and nutrition of the embryo in the early stages of development.

An enzyme called aromatase, which is part of an enzyme complex known as cytochrome P450, which is present in various organs and tissues of the body and, in particular, in some vital organs, is responsible for the production of estrogen. The aromatase enzyme in the human body is expressed in the placenta, adipose tissue, hair follicles, muscles, bones, liver and brain. In the brain, aromatase is located in the anterior and mediabasal hypothalamus.

Aromatase acts on the conversion of C19 androgens to aromatic C18 estrogenic steroids. However, aromatase is also able to metabolize xenobiotics. The ability or function of aromatase to convert adreno-androgenic substrates into estrogens is considered as the only source of estrogen in women in the postmenopausal period. Therefore, aromatase enzyme inhibitors are used to treat postmenopausal breast cancer and other estrogen-dependent diseases.

Only recently have aromatase inhibitors been found to be effective in treating breast and other estrogen-dependent diseases. The use of such inhibitors continues to increase. Aromatase inhibitors belong to a family of hormonal drugs that, both in laboratory tests and in some clinical trials, have shown significant anti-cancer activity against breast cancer diagnosed in postmenopausal women. Aromatase inhibitors are especially preferred and effective in cases where a woman has a high sensitivity to estrogen.

It has been found and is believed that more than two-thirds of breast cancers are “estrogen-sensitive” because they are able to grow and proliferate in and out of the breast. To prevent such excessive growth, the use of aromatase inhibitors has been introduced, which reduce the amount of circulating estrogen in the body of women in the postmenopausal period and, thus, cause a cessation of growth or even a decrease in estrogen-sensitive or estrogen-dependent tumors. Estrogen-sensitive malignant tumors are also called ER + (estrogen receptor positive), or, in another way, progesterone receptor positive (PR +).

Any cancer or tumor cells have receptors (binding sites) located on their cell membrane. With the production and secretion of estrogen in the body, it binds to these cellular receptors. Thus, to determine the effectiveness of inhibitory therapy, each receptor and the effectiveness of its binding to estrogen can be evaluated. This binding efficiency is commonly called "receptor status." Along with this, receptor status is responsible for the invasiveness of breast cancer.

Many aromatase inhibitors inhibit the binding of receptors to estrogen, while others inhibit aromatase enzymes whose function is the conversion of androgens to estrogens. In addition, aromatase inhibitors lower estrogen levels more efficiently after menopause, because during menopause both ovaries stop producing estrogen. However, this does not mean that estrogen is not produced at all in the body. The low estrogen levels that occur after menopause are the result of aromatase enzymes that turn other natural hormones into estrogen. Essentially, aromatase inhibitors have been developed to effectively block the production of estrogen by the aromatase enzyme. As a result, estrogen levels in the body decrease, and estrogen-dependent tumors begin to contract and disappear. On the contrary, before menopause, estrogen is mainly produced in the ovaries and only a small amount is produced as a result of the conversion process under the influence of aromatase. Numerous studies have shown that in women in the premenopausal period, aromatase inhibitors do not sufficiently reduce estrogen levels to affect tumor growth.

To date, a very limited number of aromatase inhibitors have been approved by the Food and Drug Administration and are in use. The most commonly used inhibitors are Arimidex®, Aromazin® and Femara® and all of them have passed several clinical trials. Despite the fact that they effectively inhibit aromatase enzymes, these inhibitors cause numerous undesirable side effects in patients, which makes their use in treatment less popular and less desirable. Interestingly, approved treatments for postmenopausal women include the use of drugs that both reversibly and irreversibly block estrogen receptors on the cell surface. However, their side effects include, but are not limited to, sweating, hot flashes, fatigue, changes in appetite, headache, bone pain, chest pain, cough, shortness of breath and, in some patients, thrombosis.

There are also methods for producing estrogen to increase estrogen levels in the human body. Such techniques include obtaining estrogen from the urine of pregnant horses. Despite the available technique, it has a number of side effects that are similar to side effects that occur with hormone replacement therapy, such as sweating, hot flashes, increased fatigue, changes in appetite, headache, bone pain, chest pain, cough, shortness of breath and things like that. In this regard, attempts have been made to create more advanced methods of obtaining and / or improved compositions to obtain a safe estrogen that can be used in the body.

Thus, while there are currently technologies that are used to inhibit estrogen production and for researchers and the development team to obtain estrogen for use in the body, there are still disadvantages, including undesirable side effects such as sweating, hot flashes, fatigue, and appetite changes. headache, bone pain, chest pain, cough, shortness of breath and the like. Accordingly, additional techniques or even techniques that could replace existing ones are needed in this area.

SUMMARY OF THE INVENTION

The present invention relates to estrogenic action in the human body. More specifically, the present invention relates to the use of a biologically active composition or additive for selectively inhibiting estrogen production and providing estrogenic effects in the human body, where the composition includes one or more products derived from an Indian mulberry plant, the scientific name of which is Morinda citrifolia L.

The implementation of the present invention is associated with a biologically active composition or additive obtained from the product of the Indian Mulberry plant, whose scientific name is Morinda citrifolia L. ("Morinda citrifolia"). The Morinda citrifolia product can be obtained from fruits, leaves, seeds, roots, or any other part of Morinda citrifolia. In one embodiment, the dietary supplement includes Morinda citrifolia fruit juice reconstituted from pure mashed potatoes from fruits grown in French Polynesia. The additive may also include other natural juices, for example, a concentrate of natural grape juice, a concentrate of natural blueberry juice, and / or a concentrate of other natural juice. In one embodiment, the liquid fraction is obtained from the fruits of Morinda citrifolia and used to produce a dietary supplement for consumption. In at least one embodiment, the dietary supplement is called "Tahitian Noni" ® and may be purchased from Morinda, Inc., whose main business is located at 5152 N. Edgewood Dr. # 100, Provo, UT, 84604.

In another embodiment, a dietary supplement is prepared from Morinda citrifolia leaves to produce a dry or powdered dietary supplement that can be added, for example, to a tablet form for use. In yet another embodiment, the composition is in the form of a transdermal cream that is applied to the surface of an individual's skin.

In at least several embodiments of the present invention, the dietary supplement or composition provides an estrogenic effect in the human body, and the effect of the dietary supplement or composition is milder than the action of estrogen and therefore does not cause any concomitant side effects. For example, hormone replacement therapy can cause cancer of estrogen-dependent cells in organs such as the mammary gland, uterus and / or ovaries, while the use of a biologically active supplement is preferred due to its slower excretion.

A dietary supplement or composition can serve as a replacement for estrogen in hormone replacement therapy, while its effect is weaker. In the case of a high concentration of natural estrogen, a dietary supplement will reduce the effect of natural estrogen, and at a very low concentration of natural estrogen, it will provide estrogenic activity.

In some embodiments, women are provided with a leaf extract, juice, or other Morinda citrifolia product in liquid form, in dry form in a capsule, or as a cream. In one embodiment, the patient takes at least one gram per day. Thus, in accordance with at least some embodiments of the present invention, the use or other use of a dietary supplement by an individual provides an estrogenic effect in the patient’s body to prevent or stop symptoms such as hot flashes, night sweats, bleeding, depression, which are characteristic at the onset of menopause . In addition, the dietary supplement prevents osteoporosis or improves the condition of osteoporosis.

There are two types of cells, called osteoblasts and osteoclasts, which are responsible for maintaining the normal state of bone tissue. Osteoblasts are responsible for bone remodeling, and osteoclasts are responsible for the destruction of the bone matrix. The calcium level in the blasts should be constant and the bone is a buffer to maintain calcium levels. If the level of calcium in the blood decreases, then the bone matrix will be destroyed by osteoclasts, increasing the level of calcium. During pregnancy, calcium from the mother’s blood is actively absorbed by the embryo, as its skeleton is formed. Therefore, the metabolism of the bone matrix of the skeleton of the mother increases. During pregnancy, estrogen levels are high, since estrogen is very important for processes occurring in osteoblasts responsible for bone remodeling, and during menopause, estrogen levels drop. The process of bone remodeling weakens, the woman loses the bone matrix and osteoporosis occurs. Thus, the use of the dietary supplement of the present invention can provide an estrogenic effect and compensate for the loss of bone matrix in the body. Thus, in accordance with at least some embodiments of the present invention, the processed product of Morinda citrifolia, for example leaves, juice or other parts of Morinda citrifolia, can be used to selectively provide estrogenic effects in the body.

In at least several embodiments, the dietary supplement also inhibits aromatase or aromatase enzymes whose function is to convert androgens to estrogens, thereby inhibiting the binding of receptors to estrogen and reducing and / or regulating estrogen production and also reducing the amount of estrogen produced estrogen in the body and regulating such production by inhibiting aromatase in the treatment of cancer and, in particular, in the treatment of estrogen-dependent malignant tumors by introducing into the body (for example, by ingestion) a safe, predetermined dose of a composition of a biologically active additive, which includes one or more Morinda citrifolia processed products for a predetermined, safe period of time.

In one embodiment, the Morinda citrifolia processed product is obtained in the form of fruit juice, leaves, puree juice or juice puree, fruit pulp, seed oil and / or dietary fiber using the method (s) described herein. Then, the amount of any product or combination of products was included, together with other ingredients, in the composition of a biologically active additive, which has a beneficial effect on the body and helps to treat cancer and provides prophylactic effects by inhibiting aromatase enzymes.

One embodiment of the present invention relates to a dietary supplement composition comprising at least one Morinda citrifolia processed product for inhibiting aromatase or aromatase enzymes in mammals; and the method of its introduction.

One of the embodiments of the present invention also relates to a composition of a dietary supplement, which includes at least one product obtained from one of several forms of Morinda citrifolia (preferably fruit juice or leaf powder), together with other ingredients, or natural, or synthetic, if necessary. A preferred dietary supplement composition is a liquid composition that can be administered orally or by intravenous injection, where the active ingredients, namely Morinda citrifolia, are able to be absorbed into the tissues and inhibit aromatase and reduce / regulate estrogen production.

One embodiment of the present invention relates to a method for inhibiting aromatase and treating, inhibiting, preventing and reversing the growth of cancer cells, by prophylactically using a dietary supplement composition that contains at least one Morinda citrifolia processed product as an active ingredient.

Although the methods and techniques of the present invention have been proven for specific applications in the field of selective inhibition of estrogen production and / or providing estrogenic effects in the body, one skilled in the art will understand that these methods and techniques can have a large number of different practical applications, and in large the number of different forms to obtain a composition, which includes the processing product of Morinda citrifolia to provide selective control of estrogen levels by inhibiting the production tion of estrogen and / or provide moderate estrogenic action.

These and other features and advantages of the present invention will be set forth or become fully apparent from the following description and the appended claims. Signs and advantages can be realized and obtained using the tools and combinations listed in detail in the attached claims. In addition, the features and advantages of the present invention can be studied through the practical application of the invention or will become apparent from the description set forth below.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to estrogenic action in the human body. More specifically, the present invention relates to the use of a biologically active composition or additive for selectively inhibiting estrogen production and providing estrogenic effects in the human body, where the composition includes one or more processed products of an Indian mulberry plant, the scientific name of which is Morinda citrifolia L.

The present invention relates to a method and method for producing a medicament for selectively inhibiting estrogen production and providing estrogenic effects and for treating and preventing the growth of cancer cells in mammals, as well as for reducing estrogen production, which promotes the growth of estrogen-dependent malignant tumors in mammals, by prophylactic the use of a dietary supplement composition containing at least one processed Morinda citrifolia product.

Presented preferred embodiments of the invention will be better understood, and its effects and advantages more clearly indicated, by dividing the following detailed description into parts. The first part relates to the general description of the Morinda citrifolia plant, including a description of its origin, processing methods and charitable effects on the body, as well as methods used to obtain Morinda citrifolia processed products used as the main active ingredients of dietary supplement compositions, described here; in the second part, in more detail and specifically discusses the composition and compositions, which include the processing product Morinda citrifolia, used to provide estrogenic effects; and the third part describes in more detail and specifically dietary supplement compositions and compositions, which include Morinda citrifolia processing product used to inhibit aromatase and reduce / regulate estrogen production in the body, as well as to various methods of using these dietary supplements to inhibit growth, proliferation, metastasis, and viability of estrogen-dependent cancer cells. Examples of experimental studies and the results obtained are also presented here.

Accordingly, the following description of the present invention is divided into three subheadings: “Dietary supplement”, “Providing estrogenic action” and “Inhibition of estrogen production”. Subheadings are used solely for the convenience of the reader and should not be construed as limitations.

Dietary supplement

Embodiments of the present invention relate to a dietary supplement obtained from a processed Indian Mulberry plant, the scientific name of which is Morinda citrifolia L. ("Morinda citrifolia"), which is a shrub or small tree up to 10 m high. Oval-shaped leaves are arranged on the same height against each other. Small white flowers form a fleshy, spherical, umbrella-shaped inflorescence. The fruits are large, fleshy and oval. Ripe fruits are creamy white and edible, but have an unpleasant taste and smell. This plant is native to Southeast Asia, but in ancient times it spread over a vast area from India to eastern Polynesia. A wild plant grows randomly, while a cultivated one grows on plantations and small private areas. Morinda citrifolia flowers are small, white, three-five-petalled, cylindrical, fragrant, about 1.25 cm long. The flowers develop into complex fruits, consisting of many small stone fruits combined in an ovoid, ellipsoid or round, rough body, with a waxy, white or greenish-white or yellowish, translucent skin. On the surface of the fruit there are "eyes" similar to potato. Juicy, unpleasant to the taste, dull yellow or yellowish-white fruit contains numerous red-brown, firm, oblong-triangular, winged 2-cell bones, each of which contains four seeds.

A fully ripe fruit has a pronounced smell, similar to rotten cheese. Although the fruits were used as food by some nationalities, most often Morinda citrifolia plants were used as a source of red and yellow paint. Recently, interest has been shown in the Morinda citrifolia plant in terms of nutritional and health effects on the body, discussed below.

Since in all practical applications the fruit of Morinda citrifolia is inedible, the fruit must be processed in such a way as to make it palatable to humans, and included in a dietary supplement used to provide estrogenic effects, aromatase inhibition and effects on various malignant cells. The processed Morinda citrifolia fruit juice can be obtained by separating the seeds and skin from the juice and pulp of the ripened Morinda citrifolia fruit; separating juice from pulp by filtration; and packaging juice. Alternatively, instead of packaging the juice, the juice can be immediately included as an ingredient in another food product, frozen or pasteurized. In some embodiments, the juice and pulp may be processed into a homogeneous mixture for mixing with other ingredients. Another technique involves freezing the fruit and juice. The fruit and juice can be restored upon receipt of the final juice product. Other techniques include air drying the fruit and juices before grinding.

Embodiments of the present invention provide for the extraction of a Morinda citrifolia product from Morinda citrifolia leaves and its use in capsule or tablet compositions to inhibit estrogen production and provide estrogenic effects in the body.

Embodiments of the present invention also include the use of fruit juice and / or fruit puree obtained from a Morinda citrifolia plant. In this preferred method for producing Morinda citrifolia fruit juice, the fruits are harvested manually or using mechanical equipment. Fruits can be harvested when their size reaches at least 1 inch (2-3 cm) to 12 inches (24-36 cm) in diameter. Preferably, the color of the fruit may be dark green, yellow-green, white and their intermediate shades. After harvesting, the fruit is washed thoroughly before any further processing.

The fetus is left to ripen or withstand from 0 to 14 days, most often 2-3 days. The fetus matures or is kept in the device so that it does not come into contact with the ground. During ripening, the fetus is preferably wrapped in cloth or mesh material, but the fetus can ripen without it. The fruit is ready for further processing if its color becomes light, light green, light yellow, white or translucent. The fetus is carefully examined for spoilage or excessively green in color and hardness. A spoiled or hard green fruit is separated from suitable fruits.

Preferably, the ripened fruits and the fruits that are kept for further processing and transportation are placed in sealed plastic containers. Ripe fruit containers can be stored from 0 to 30 days. Most often, containers with fruits are stored for 7-14 days before processing. If desired, containers can be stored in cold conditions before further processing. After being removed from the containers, the fruits are subjected to manual or mechanical sorting. Seeds and peel are separated from juice and pulp.

Juice and pulp can be packed in containers for storage and transportation. Alternatively, the juice and pulp can be immediately processed into the final juice product. Containers can be stored in cold conditions, frozen or at room temperature.

The juice and pulp of Morinda citrifolia is preferably mixed to a homogeneous mixture, which can then be mixed with other ingredients, for example, flavors, sweeteners, nutritional components, plant components and colorings. The final juice product is preferably heated and pasteurized at a minimum temperature of 181 ° F (83 ° C) or at a maximum temperature of 212 ° F (100 ° C).

Another product obtained from Morinda citrifolia is mashed potatoes and juice puree, either in the form of a concentrate or in a diluted form. Essentially, the puree is the pulp of the fruit, separated from the seeds, and is different from the fruit juice of another product described here.

Each product is placed and sealed in a final container of plastic, glass or other suitable material that can withstand the processing temperature. The containers are left at the temperature at which filling took place, or they can be quickly cooled and placed in a shipping container. Preferably, the shipping containers are wrapped in material in order to maintain or control the temperature of the product in the final containers.

Juice and pulp can then be separated through a filter unit. Preferably, the filter unit consists of, but is not limited to, a centrifuge bowl, a mesh filter ranging in size from 1 micron to 2000 microns, more preferably less than 500 microns, from a filter press, reverse osmosis unit and any other standard commercial filtration devices. Preferably, the working pressure of the filtration is in the range from 0.1 psi to about 1000 psi. A preferred flow rate is from 0.1 g / min to 1000 g / min and, more preferably, between 5 and 50 g / min. Juicy, fresh pulp is washed and filtered at least once and up to 10 times in order to remove all juice from the pulp. Fresh pulp usually contains 10-40% by weight of fiber. Preferably, fresh pulp is pasteurized at a minimum temperature of 181 ° F (83 ° C) and then packaged in a cylindrical box for further processing or preparation of a fiber-rich product.

Dietary fiber can also be a Morinda citrifolia processed product. In addition, the Morinda citrifolia processing product may be in the form of an extract (e.g., a powdered extract) extracted from Morinda citrifolia leaves. Also, the Morinda citrifolia processing product may be in the form of an oil. Morinda citrifolia oil usually contains a mixture of several different fatty acids, for example triglycerides, such as palmitic, stearic, oleic and linolenic fatty acids, and other fatty acids that are present in smaller amounts. In addition, the oil preferably contains an antioxidant that inhibits the degradation of the oil. Preferably, conventional dietary antioxidants are used.

Morinda citrifolia is rich in natural ingredients. For example, natural ingredients include: (in leaves) alanine, anthraquinones, arginine, ascorbic acid, aspartic acid, calcium, beta-carotene, cysteine, cystine, glycine, glutamic acid, glycosides, histidine, iron, leucine, isoleucine, methionine , nicotinic acid, phenylalanine, phosphorus, proline, resins, riboflavin, serine, beta-sitosterol, thiamine, threonine, tryptophan, tyrosine, ursolic acid and valine; (in colors): acacetin-7-o-beta-d (+) - glucopyranoside, 5,7-dimethyl-apigenin-4'-o-beta-d (+) - galactopyranoside, and 6,8-dimethoxy-3 methylanthraquinone-1-o-beta ramnosyl-glucopyranoside; (in fruits) acetic acid, asperuloside, butyric acid, benzoic acid, benzyl alcohol, 1-butanol, caprylic acid, decanoic acid, (E) -6-dodeceno-gamma-lactone, (Z, Z, Z) -8, 11,14-eicosatrienoic acid, elaidic acid, ethyl decanoate, ethyl hexanoate, ethyl octanoate, ethyl palmitate, (Z) -6- (ethylthiomethyl) benzene, eugenol, glucose, heptanoic acid, 2-heptanone, hexanolic hexane, , caproic acid (hexanoic acid), 1-hexanol, 3-hydroxy-2-butanone, lauric acid, limonene, linoleic acid otu, 2-methylbutanoic acid, 3-methyl-2-buten-1-ol, 3-methyl-3-buten-1-ol, methyl decanoate, methyl elaidate, methyl hexanoate, methyl 3-methylthio-propanoate, methyl octanoate, methyl oleate, methyl palmitate, 2-methylpropanoic acid, 3-meltiopropanoic acid, myristic acid, nonanoic acid, octanoic acid (caprylic acid), butyric acid, palmitic acid, potassium, scopoletin, undecanoic acid, (Z, Z) -2,5-undecadiene- 1-ol and womifol; (in the roots) anthraquinones, asperuloside (rubichloric acid), damnacanthal, glycosides, morindadiol, morindin, morindon, mucous substance, nordamnacanthal, rubiadin, rubyadine monomethyl ether, resins, coranjidiol, sterols, and anthraquinone methyl ether; (root bark) alizarin, chlororubin, glycosides (pentose, hexose), morindadiol, morindanigrin, morindine, morindone, a gummy substance, rubidium monomethyl ether, and soranidiol; (from wood) anthragallol-2,3-dimethylether; (from tissue culture) damnacanthal, lucidin, lucidin-3-primeroside, and morindone-6-beta-primeroside; and (from a plant) alizarin, alizarin alpha-methyl ether, anthraquinones, asperuloside, caproic acid, morindadiol, morindone, morindogenin, octanoic acid, and ursolic acid.

As indicated, it has recently been discovered that the use of products containing Morinda citrifolia is good for health. It has been found that Morinda citrifolia is capable of secreting and producing xeronine, which is a relatively small alkaloid physiologically active in the body. Xeronine is found in almost all healthy cells of plants, animals and microorganisms. Although the Morinda citrifolia plant has a negligible amount of free xeronine, it does contain a significant amount of a xeronin precursor called proxeronin. Moreover, Morinda citrifolia contains an inactive form of the proxeronase enzyme, which converts proxeronin to xeronine. A publication by R.M. Heinicke of the University of Hawaii, "The Pharmacologically Active Ingredient of Noni" states that Morinda citrifolia is "the best starting material for xeronine excretion," due to the presence of building blocks of proxeronin and proxeronase. These building blocks contribute to the release and production of xeronine in the body. The essential nutrient xeronine has four functions.

First, xeronine serves as an activator of small intestine enzymes. These enzymes are essential for effective digestion, have a calming effect on the nerves and are necessary for the overall physical and emotional state. Secondly, xeronin protects and maintains the shape and flexibility of protein molecules so that they can pass through cell walls and be used to form healthy tissue. Without these nutrients entering the cell, the cell cannot effectively do its job. Without proxeronin producing xeronine, cells, and subsequently the body, suffer. Thirdly, xeronine helps to increase the pores of cell membranes. This increase allows larger polypeptide chains (amino acids or proteins) to enter the cell. If these circuits are not used, they are disposed of. Fourth, xeronine derived from proxeronin promotes pore enlargement, thereby contributing to better absorption of nutrients.

Each tissue has cells that contain proteins that have receptor sites for the absorption of xeronine. Some of these proteins are inert forms of enzymes, the activation of which requires the absorption of xeronine. Thus, xeronine quickly and safely removes dead tissue from the skin by converting the body's procollagenase system into specific proteases. Other proteins, after interacting with xeronine, acquire potential receptor sites for hormones. Thus, the ability of Morinda citrifolia to improve the condition of a person is possibly related to the ability of xeronine to convert certain receptor proteins of the brain into active sites for the absorption of endorphin, the hormones of well-being. Other proteins form the pores of the membranes of the intestines, blood vessels, and other organs. The absorption of xeronine by these proteins changes the shape of the pores and, thus, affects the passage of molecules through the membrane.

As a result of its beneficial effects, Morinda citrifolia is known to provide many incredible effects in cancer patients suffering from arthritis, headaches, digestive disorders, malignant neoplasms, bone fractures, high blood pressure, diabetes, pain, infection, asthma, toothache, spots on the skin, immunodeficiency and the like.

Compositions containing Morinda citrifolia may be. in a form suitable for oral administration, systemic administration, injection and the like. As for the oral composition, such a composition may exist, for example, in the form of tablets or lozenges, aqueous or oily suspensions, dispersed powders or granules, emulsions, syrups or elixirs. Compositions intended for oral administration may be prepared by any method known in the art for the preparation of Morinda citrifolia compositions, and such compositions may contain one or more agents selected from the group consisting of sweeteners, flavoring agents, coloring agents and preservatives. Tablets contain Morinda citrifolia mixed with non-toxic pharmaceutically acceptable inert excipients that can be used to make tablets. These inert fillers may be, for example, inert diluents, granulating and disintegrating agents, binding agents and lubricants. The tablets may be uncoated, or may be coated using known techniques to avoid degradation and absorption in the gastrointestinal tract, which provides a long-term effect. For example, delayed-action materials such as glyceryl monostearate or glyceryl distearate can be used.

Aqueous suspensions contain Morinda citrifolia mixed with inert excipients that can be used to prepare aqueous suspensions. Such inert fillers are suspending agents, for example sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, sodium alginate, polyvinyl pyrrolidone, tragacanth gum and Arabian gum; dispersing or moisturizing agents may be natural phosphatides, for example lecithin, or condensation products of alkylene oxide with fatty acids, such as polyoxyethylene stearate, condensation products of ethylene oxide with long chain aliphatic alcohols, such as heptadecaethylene-oxetsetanol, or condensation products of ethylene oxide and non-fatty acids hexite, such as, for example, polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty hexite acids and anhydrides, for example polyethylene sorbitan monooleate.

Thus, embodiments of the invention selectively inhibit estrogen production and provide an estrogenic effect. In some embodiments, the liquid or dry extract comprises a processed product of Morinda citrifolia. In still other embodiments, the product is provided in capsule form to facilitate administration. In some embodiments, at least one gram is applied daily until symptoms disappear.

Providing estrogenic action

As described above, the present invention relates to the control of estrogenic activity in the human body. More specifically, the present invention relates to the use of a biologically active composition or additive for selectively inhibiting estrogen production and providing estrogenic effects in the human body, where the composition includes one or more products derived from an Indian mulberry plant, the scientific name of which is Morinda citrifolia L.

Phytoestrogens are certain compounds found in plants that have a similar effect with natural estrogens. Plants rich in phytoestrogens are black cohosh (Cimicifuga racemosa), soybeans (Glycine max.), Red clover (Trifolium pratense) and hops (humulus lupulus). Data from studies conducted by the inventors show that Morinda citrifolia (fruits and leaves) also exhibits estrogenic activity. This is confirmed by the fact that women who eat foods rich in phytoestrogens have fewer health problems during menopause.

The estrogenic activity of the Morinda citrifolia leaf alcohol extract was investigated by two in vitro methods. (1.) Replacing estrogen on an isolated alpha and beta receptor (ER-alpha, ER-beta); and (2.) Introduction of alkaline phosphatase into Ishikawa cells (human endometrial carcinoma). Used alcohol extract of crushed dry leaves of Morinda citrifolia (grown in Tahiti). One milliliter of extract contains 100 μl of leaves.

In the case of estrogen replacement, recombinant ER-alpha and ER-beta were used. The receptors were saturated with tritium-labeled estradiol. After adding the test substance, free unbound radioactivity was measured. The method used was based on a publication by Kuiper et al., 1998. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der B B and Gustafsson JA (1998) Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor Beta. Endocrinology 139: pp 4252-4263.

The results showed that a steady replacement of estradiol occurred in both receptors. Substitution of estrogen reached 100% level, which is typical for phytoestrogens. The affinity of the leaf extract for ER-alpha was almost 5 times greater than for ER-beta (see figure 1).

Induction of the alkaline phosphatase enzyme is controlled by estrogen receptors. Estradiol is known to have a regulatory function in bone remodeling. Alkaline phosphatase is a key enzyme in this process. Ishikawa cells were used as a model to study the agonist effects of compounds with estrogenic activity (Wober J, Weisswange I and Vollmer G (2002) Stimulation of Alkaline Phosphatase Activity in Ishikawa Cells Induced by Various Phytoestrogens and Synthetic Estrogens. J Steroid Biochem Mol Biol 83: pp 227-233).

Morinda citrifolia leaf extract exerts a medium but significant induction of alkaline phosphatase into Ishikawa cells. The maximum effect was obtained at a concentration of 0.3 ml / ml (corresponding to 30 mg of dry leaves / ml). Higher concentrations inhibited the induction of the enzyme (see figure 2).

Accordingly, the estrogenic activity of the Morinda citrifolia leaf alcohol extract was shown in two in vitro assays commonly used to study estrogenic activity. Both analyzes showed beneficial effects. The results suggest the possible use of Noni leaves to treat symptoms caused by estrogen deficiency (for example, with menopause and ovariectomy).

Phytoestrogens and estrogen-like molecules are able to bind estrogen receptors, which in turn can cause an effect similar to the action of estrogen in cells and tissues. Recently, selectivity for selective estrogen receptor modulators (SERMs) has been demonstrated for soy isoflavones, which has a beneficial effect on the body without causing unwanted effects. Beneficial effects may include the prevention of breast cancer and may cause stunting and, in some cases, cause apoptosis of prostate cancer cells in vitro and in vivo, and may also prevent osteoporosis.

As reported, some phytoestrogens have anti-androgenic effects and antioxidant properties. Mechanisms include inhibition of 5α-reductase, 17β-hydroxysteroid-dehydrogenase, aromatase, tyrosine-specific protein kinase, and DNA topoisomerase II. One of the best explanations for the biological activity of estrogen-like molecules is that phytoestrogens have weak estrogenic effects, but stimulate a certain activity of ER agonists and ER antagonists, which depend on the cell environment and promoter, and suggest that such compounds with weak estrogenic activity stimulate tissue-specific activity of ER agonists or antagonists.

Some studies have shown that some phytoestrogens can inhibit enzymes that convert androgens to estrogens, namely aromatase and 17β-hydroxysteroid dehydrogenase type 1 & 5, and not others. As presented below, a dietary supplement containing Morinda citrifolia processing product inhibits the aromatase enzyme. Such a dietary supplement also provides estrogenic effects.

Tahitian Noni® juice has high antioxidant properties compared to pycnogenol. Compounds with an estrogen effect have been found to prevent brittle bone disease in mice, but do not cause side effects. This finding can be used to help and relieve the need for older women who have stopped using hormone replacement therapy (HRT) because of the risk of developing cancer and heart disease that are associated with HRT.

Previously, hormone replacement therapy (HRT) with estrogen and estrogen derivatives was used to prevent osteoporosis, but it is no longer used in some countries due to side effects. Thus, the use of hormone replacement therapy is limited for severe symptoms, but it is advisable for women to treat with moderate symptoms because they cause inconvenience.

The possible estrogen agonistic effect of the dry form of the Tahitian Noni® juice puree concentrate (TNPJC) of immature female ICR mice at a maximum tolerated dose of 4000 mg / kg administered orally once a day for three consecutive days was evaluated. A dry form of TNPJC was prepared using Rotor Vap under pressure and at low temperature.

It was found that the administered dose of 4000 mg / kg causes a 50% increase in the total uterine mass (not dry matter mass) relative to the comparison group (0.03 mg / kg β-estradiol 3-benzoate increases the total uterine mass by 83%) which shows a possible estrogen agonistic activity. This may also suggest dose dependence.

A huge dose of dry form TNPJC causes a 50% increase, while a negligible dose (0.03 mg / kg) of estradiol-3-benzoate causes the significant weight gain observed above.

Briefly, Tahitian Noni juice puree concentrate has anti-aromatase effects, anti-cancer, antioxidant and other beneficial effects, Tahitian Noni prevents the side effects of estrogen-like compounds, and also has estrogen-like effects in a selected dose, which can explain the benefits for women in premenopausal and the postmenopausal period, such as the prevention of osteoarthritis, osteoporosis and other beneficial effects, have already been mentioned above.

In accordance with embodiments of the present invention, a dietary supplement containing a Morinda citrifolia processed product provides a mild estrogenic effect. Natural hormones have a very fast cycle, as they are secreted by non-somatic processes and, therefore, in order to guarantee a fast control system, it is necessary to gain control over the regulator, which is the hormone, and the only way to control it is to remove it in order to release a new hormone system. Thus, if we consider natural estrogen, the half-life of this component is very short. Thus, to ensure a constant level of the hormone, it is necessary to use a compound that has an action similar to natural hormone but is not removed from the system so quickly due to some chemical changes in the molecule.

For example, a steroid compound contains 1 estrogen group in this system, and natural enzymes that remove estrogen from the bloodstream cannot convert a derivative, so it remains active for a long time in the body. For continuous treatment for several days or weeks, you cannot use natural hormone, you must use derivatives that are more slowly excreted from the body. Accordingly, a dietary supplement with a Morinda citrifolia processed product can be used. This dietary supplement acts in a similar way to natural hormone and has a strong effect. The action is very strong and sometimes stronger than that of the natural hormone, so the side effects of the hormone are exacerbated by the action of these compounds. Phytoestrogens are not estrogens from a chemical point of view, but from a biological point of view, they are estrogens. Since they have an estrogenic effect, they interact with the system and have a similar, but not the same, reaction or consequences with estrogen. Their action is weaker and has no peaks.

In the presence of estrogen, their action may be antagonistic to the action of estrogen. Thus, there are many opinions on the feasibility of using natural estrogens. Women who eat foods rich in phytoestrogens are less likely to develop breast cancer and have fewer problems during menopause. Phytoestrogens are found in various natural foods, especially in soy and other plants. Soy is rich in phytoestrogens and women in Japan and China consume a lot of soy products.

According to at least some embodiments of the present invention, a dietary supplement containing a processed product of Morinda citrifolia may be in the form of capsules or cream, for example, a cream penetrating through the skin or through mucous membranes.

The absorption rate of processed Morinda citrifolia leaves when ingested is high. In order to detect a compound with estrogenic action, a certain limit value is necessary. The function of estrogen in the body or cells is to detect a receptor in the cell, and then bind to this receptor, then this estrogen-receptor complex binds to DNA and stimulates the induction of certain proteins, which are then produced by the cells and, thus, this is their mechanism of action. Thus, in order to detect estrogenic action, this mechanism of action can be followed.

At first it was shown that the compound binds to the receptor to saturate the receptor with natural estrogen in a radioactive form, after adding another compound to the receptor, this compound will displace estrogen from the receptor, due to competition for the receptor site between natural estrogen and another estrogen. If the compound binds, estrogen is released. We can say that binding is the first stage, and the second stage is the connection of the estrogen – receptor complex with DNA and the stimulation of the induction of certain proteins.

A compound can bind an estrogen receptor, but not exhibit an estrogenic effect; if it exhibits this action, it acts as an antagonist. After this, the action of estrogen is inhibited, since the receptor is busy, estrogen cannot find a free receptor and, as a result, cannot act. Thus, the authors searched for compounds that bind the receptor and then act as estrogen. This leads to the functioning of some proteins. Therefore, both studies were carried out. First, receptor binding was investigated, and secondly, an endpoint was determined.

Morinda citrifolia leaf extract acts like estrogen and provides estrogenic effects. However, the effect of the extract is weaker than the action of natural estrogen, so it does not cause side effects.

An adverse effect of hormone replacement therapy is that it can provoke cancer of estrogen-dependent cells, such as breast, uterus, and ovarian cancer, when treated with high doses of estrogen or synthetic estrogens derived from natural estrogen, but having a longer duration of action for lower excretion. If women are treated with high doses of estrogen for a certain period of time, maybe years, it can cause breast cancer, or uterine cancer, or ovarian cancer, especially breast cancer and endometrial cancer.

Therefore, often women refuse hormone replacement therapy, but need another weaker substitute for hormone replacement therapy. What is interesting for these compounds is that at high concentrations of natural estrogen they act as antagonists, which means that they weaken the effect of natural estrogen, and at very low concentrations of natural estrogen they act like estrogen, thereby supporting an estrogenic effect or have estrogenic effects. This means that these compounds will help even out estrogen concentrations, thereby helping women avoid emergencies.

Symptoms that usually occur in women during the onset of menopause and sometimes until the menstruation ceases forever include flushing, night sweats, and / or depression. Bleeding and depression can be very severe. Another effect of long-term use is osteoporosis, which results in a constant change in the bone matrix. The bone matrix is degraded and reconstructed again. There are two types of cells responsible for this process, called osteoblasts and osteoclasts. Osteoblast cells are necessary for bone remodeling, and osteoclast cells are responsible for bone degradation, which is very important because the calcium level in the blasts must be constant and the bone is a buffer of calcium level. With a decrease in the level of calcium in the blood, degradation of bone substance and an increase in the level of calcium occur. During pregnancy, calcium from the mother’s blood is actively absorbed by the embryo to build the skeleton. Thus, the consumption of the bone matrix of the skeleton of the mother during pregnancy should increase. At the same time, the level of estrogen increases during pregnancy, since estrogen is important for the process that takes place in osteoblast cells that rebuild bones, and during menopause, the level of estrogen decreases and the process of adjustment becomes weaker, the bone matrix gradually breaks down and osteoporosis occurs .

To determine the activity of the MDA-6 compound (RT # 1026431), enzymatic analysis and radioligand binding analysis were performed. The methods used in this study to achieve maximum reliability and reproducibility were adapted based on the scientific literature. In each study, reference standards were used to ensure the reliability of the results. Studies were carried out under the conditions described in the accompanying section "Methods" of this description. Literary reference (s) for each study are given in the section "Literary references".

Presents the value determined by the IC ₅₀ non-linear least squares regression method using the Data Analysis Toolbox ™ (MDL Information Systems, San Leonardo, California, USA), where K _i is the inhibition constant, and K _i was calculated using the Cheng and Prussoff equation (Cheng, Y., Prusoff, WH, Biochem. Pharmacol. 22: 3099-3108, 1973) using the experimental IC ₅₀ value of the test compound, the concentration of the radioligand used in the study, and the initial K _d ligand value (obtained experimentally in MDS Pharma Services). The presented Hill coefficient, which determines the slope of the competitive binding curve, was calculated using the Data Analysis Toolbox ™. Hill coefficients, significantly different from 1.0, suggest that the binding bias does not follow the laws of the existing masses with a single binding site. Where IC ₅₀ , K _i , and / or n _H data are presented without standard error (SEM), data are insufficient to be quantitative, and reported values (IC ₅₀ , K _i , n _H ) should be interpreted with caution.

A summary of the results is shown in the following table in order of ranking the effectiveness of the calculated values of IC ₅₀ and / or K _i . The results of biochemical studies are presented as a percentage of inhibition of specific binding or activity. All other results are expressed in terms of quantification, respectively, studies are shown in the table. For primary studies, only low concentrations with a significant response met the study criteria. It also shows either the results of the retest when the low dose / concentration meets the criterion of significance, or in the case of inactivation when the highest dose / concentration does not meet the criterion of confidence, if such tests were carried out. If such tests were not required, then primary repeat screenings with quantitative indicators are shown (for example, IC ₅₀ ± SEM, K _i ± SEM and n _H ). When screening shows the initial screening with repetition with semi-quantitative data (for example, calculated values of IC ₅₀ , K _i and n _H ), where possible (concentration range of 4 logarithmic units); secondary functional analyzes, if any, were performed at 30 μm, and MEC or MIC was determined only when the activity in the primary tests was> 50% at a concentration of 1 log unit lower than the initial test. Significant responses (≥50% inhibition or stimulation for biochemical studies) noted in the primary studies are listed below.

136010 Lipogenase 5-LO

Source: human PBMN cells

Substrate: endogenous arachidonic acid from PBMNC

Thinner: 100% H ₂ 0

Pre-incubation time / temperature: 15 minutes / 37 ° C

Incubation time / temperature: 15 minutes / 37 ° C

Hatching Buffer: HBSS (Hanks Balanced Salt Solution)

Quantification Method: EIA LTB ₄ Quantification

Reliability criterion: ≥50% of maximum stimulation or inhibition

226010 Estrogen ER

Source: recombinant human and insect Sf9 cells

Ligand: 0.5 nM ³ H estradiol

Thinner: 100% H ₂ O

Incubation time / temperature: 2 hours / 25 ° C

Incubation buffer: 10 mM Tris-HCl, pH 7.5, 10% glycerol, 1 mM DTT, 1 mg / ml BSA

Nonspecific ligand: 1 μM diethylstilbestrol

K _d : 0.2 nM *

B _max : 1400 pmol / mg protein *

Specific binding: 85% *

Quantification Method: radioligand binding

Reliability criterion: ≥50% of maximum stimulation or inhibition

250 600 Leukotriene D 4

Source: Hartley Guinea Pig Light

Ligand: 0.2 nM ³ H leukotriene D ₄ (LTD ₄ )

Thinner: 100% H ₂ O

Incubation time / temperature: 60 minutes / 25 ° C

Incubation buffer: 50 mM Tris-HCl, 0.01% BSA, 5 mM CaCl ₂ , 5 mM MgCl ₂ , bacitracin 100 μg / ml, 1 mM phenylmethylsulfonyl fluoride.

Nonspecific Ligand: 0.1 μM Leukotriene D ₄ (LTD ₄ )

K _d : 0.2 nM *

B _max : 0.24 pmol / mg protein *

Specific binding: 85% *

Quantification Method: radioligand binding

Reliability criterion: ≥50% of maximum stimulation or inhibition

226050 Estrogen ERβ

Source: recombinant human and insect Sf9 cells

Ligand: 0.5 nM ³ H estradiol

Thinner: 100% H ₂ O

Incubation time / temperature: 2 hours / 25 ° C

Incubation buffer: 10 mM Tris-HCl, pH 7.5, 10% glycerol, 1 mM DTT, 1 mg / ml BSA

Nonspecific ligand: 1 μM diethylstilbestrol

K _d : 0.13 nM *

B _max : 3000 pmol / mg protein *

Specific binding: 90% *

Quantification Method: radioligand binding

Reliability criterion: ≥50% of maximum stimulation or inhibition

271200 Serotonin 5-HT _1B

Source: Wistar Rat Cortex

Ligand: 10 pM ^l25 I CYP

Thinner: 100% H ₂ O

Incubation time / temperature: 90 minutes / 37 ° C

Incubation buffer: 50 mM Tris-HCl, 154 mM NaCl, 10 μM pargyline, 30 μM isoprenaline, pH 7, 7

Nonspecific Ligand: 10 μM Serotonin (5-HT)

K _d : 0.19 nM *

B _max : 0.14 2 pmol / mg protein *

Specific binding: 70% *

Quantification Method: radioligand binding

Reliability criterion: ≥50% of maximum stimulation or inhibition

Accordingly, it has been shown that estrogen receptors have a higher ability to bind NSAID ligands with higher affinity. Most of these ligands, a mixture of agonists and antagonists, have been developed and used in the treatment of postmenopausal women. Moreover, steroid estrogens play not only an important role in the development of the body, but also in the differentiation of certain cells, the functioning of the male and female reproductive systems, have a positive effect on osteoblasts and their functions, the cardiovascular and central nervous systems.

The effects described above are mediated by two intranuclear proteins, such as ERα and ERβ. The binding of estrogens or estrogen-like molecules to these intranuclear proteins leads to structural conformational changes, which, in turn, dimerizes the ligand-receptor complex and leads to the activation of genes controlled by DNA.

It has been documented that xenoestrogens, phytoestrogens and synthetic estrogens are able to bind to those estrogen receptors, which in turn mimic the effects of human estrogen in a specific cell and tissues in a specific way, such as those that are well known in reproductive systems. However, estrogen and estrogen-like molecules and its receptors can act in various areas throughout the body and, in particular, in the brain. Estrogen and estrogen-like molecules act as a powerful neuroprotective antioxidant that can activate gene transcription to provide direct or indirect neuroprotective effects.

Any compounds that, through these receptors of nuclear proteins, can have either a stimulating effect (agonist) on certain tissues (e.g. bone tissue and as an antagonist on other tissues) and a blocking effect (antagonist) in other tissues (e.g. breast cancer and cancer uterus). Some recent scientific studies suggest that in the regulation of heart rate and heart rate ERα, the form is more significant than ERR. Thus, several assumptions have been made regarding a selective ERα antagonist for effective control of cardiac activity.

To evaluate the activity of Tahitian Noni® juice puree concentrate, an experimental study of radioligand binding was carried out to establish the effects of Tahitian Noni® Puree juice puree and Tahitian Noni® juice on estrogen receptors ERα and ERβ, and the following results were obtained:

1% Tahitian Noni juice puree concentrate = 99% inhibition of ERα with IC ₅₀ 0.31%

1% Tahitian Noni juice puree concentrate = 99% inhibition of ERβ with IC ₅₀ 0.28%

2% Tahitian Noni® Juice = 20% ERα Inhibition

2% Tahitian Noni® juice = 40% inhibition of ERβ

Based on these results, it can be assumed that there is a dose-dependent effect of Tahitian Noni® juice on the inhibition of estrogen receptors ERα and Erβ, respectively, compared with the concentrate of Tahitian Noni juice puree in these in vitro studies. Moreover, these results show that Tahitian Noni® juice and Tahitian Noni juice puree concentrate have a beneficial cardioprotective effect and are effective in treating symptoms of postmenopause, osteoarthritis, breast cancer, uterine cancer, and colon cancer.

The following describes the estrogen agonist activity of Morinda citrifolia processed products. This means that estrogen is a hormone with many properties, and this hormone is necessary to maintain the balance of the internal system. Thus, estrogen is necessary for the connection of the nervous system and the endocrine system and is especially important for the reproductive system, which makes it possible for children to be born, while it is involved not only in the stages of pregnancy, but also in the stages of the formation of a woman’s attractiveness for men, that is, estrogens form secondary sexual signs, smooth skin and so on. In the body, estrogen regulates various cells, performing a special role in each organ. This role is to proliferate, for example, the uterus, for example, at the time of fertilization should be sensitive to receiving an egg, and then feed it, and then, with the growth of the embryo, new blood vessels must grow from the uterus and enter the embryo to feed it, therefore, estrogen can induce proliferation of cells, and during pregnancy, the mass of the entire uterus increases, therefore, cell division is enhanced in this organ.

And the same goes for the mammary gland. The mammary gland must grow in order to produce milk after the birth of a baby, therefore, estrogen induces the growth of these cells too. The development of cancer begins with cell growth, but usually the cells stop growing at the right time, but sometimes they mutate and the cell growth does not stop, and compounds that induce cell growth can contribute to tumor formation by cancer cells, and this is why estrogen increases the incidence of cancer in these cells. organs, because estrogen induces the growth of uterine and breast cells. Another action of estrogen is, for example, the induction of the synthesis of a specific protein of the angiotensin in the liver, which regulates blood pressure and much more. It also regulates mood processes in the brain. Estrogen contributes to the well-being and mood of women during gestation and the birth of a child, and with its deficiency, depression often occurs. In men, estrogen also has some activity (estrogen is not a purely female hormone, men also have estrogen). In small concentrations and after menopause in women, the level of estrogen concentration decreases to the concentration of estrogen in men.

Usually, men do not receive treatment with synthetic estrogens, except when they have prostate cancer, since in men testosterone has the same effect on prostate cells, and thus on sexual functions, as estrogen has on female sexual functions, and especially testosterone enhances the growth of prostate cells, and in the presence of single malignant cells and a high level of testosterone, they can develop into a tumor and form prostate cancer Esa, both testosterone and estrogen are antagonists, and when treating men with estrogen, it has an antagonistic effect on testosterone and reduces the growth of prostate cells. This is the basis for the treatment of men with prostate cancer with estrogen. At the same time, female signs begin to appear in them, for example, their breasts begin to grow, their beard stops growing, and the like, but vital estrogens do not cause such symptoms, since they are reactive. Thus, when taking vital estrogens, men do not lose sexual functions, or they do not observe any changes in their phenotype. At the same time, vital estrogens do not reduce the growth of prostate cells and do not reduce the risk of prostate cancer, which could be another useful property of vital estrogens expressed in men.

The possible estrogen agonistic effect of the test substance TNCONC was evaluated in immature female ICR mice, at a maximum tolerated dose of 4000 mg / kg, administered orally once a day for three consecutive days. Significant estrogen agonistic activity, which was manifested by a change in the fresh mass of the uterus, was observed for TNCONC (a 50% increase compared with the placebo group). Each of the test animals showed an increase in the intestines; however, no changes in behavior were observed during the test period. It was concluded that oral dose of TNCONC at a dose of 4000 mg / kg (PO) has significant estrogen agonistic activity in mice.

The following are materials and equipment:

1. Test Substances and Dosage Regimen — TNCONC, provided by Morinda, Inc., was dissolved in 2% Tween 80 / 0.9% NaCl. For testing, the maximum tolerated dose of 4000 mg / kg was administered intraperitoneally daily for three consecutive days and a dose of 10 ml / kg was used.

2. Animals - used female ICR mice provided by MDS Pharma Services - Taiwan Ltd. The distribution of space for 5 animals was 29 × 18 × 13 cm. The animals were placed in APEC ¹¹ cells and kept in an environment with controlled temperature (22 ° C-24 ° C) and humidity (60% -80%) with 12-hour cycles of the day and nights at least one week before the experiment at the MDS Pharma Services-Taiwan Laboratory. They were given free access to commonly used laboratory rat food (Lab Diet, Rodent Diet, PMI Nutrition International, USA) and tap water. All aspects of this work, including the placement, experimental part and processing of animals, were carried out mainly in accordance with the International Guiding Principles for Biomedical Research Involving Animals (CIOMS Publication No. ISBN 92 90360194, 1985).

3. Reagents - β-estradiol 3-benzoate (Sigma, USA), pyrogen-free saline solution (Sinton, Taiwan) and Tween 80 (Wako, Japan).

4. Equipment - animal cells (ShinTeh, R. O. S.), electronic scales 0.0001 g - 9.9999 g (R160P, Sarturius, Germany), glass syringe (1 ml, 0.5 ml Mistuba, Japan) hypodermic needle (26 G × 1 ", TOP Corporation, Japan), oral needle for mice, stainless steel scissors (Klappencker, Germany).

The test substance was administered at a maximum tolerated dose of 4000 mg / kg intraperitoneally (IP) for three consecutive days to a group of five immature female ICR mice weighing 13 ± 1 g. Animals were scarified 24 hours after the final dose and the wet weight of the uterus of each animal was measured. An increase in uterine wet weight of 50 percent or more (≥50%) compared with the control group of animals indicates a possible estrogen agonistic activity. The following table presents the results of the study:

Table 1 Protocol 9531000 estrogen-agonistic effect in mice Treatment Processing path Dose No. Uterine Weight (mg) % reduction Individual Average Carrier IP 10 ml / kg one 14.9 (2% Tween 80 / 2 16.1 0.9% NaCl) 3 14.7 four 18.0 5 14.6 15.7 - PT # 1026431- IP 4000 mg / kg one 23,4 ADD (MDA-6) 2 23.5 (TNCONC) 3 27.5 four 19.6 5 23.5 23.5 (fifty) β-estradiol PO 0.03 mg / kg one 28.7 3-benzoate 2 20.7 3 31.3 four 35.6 5 34.9 30,2 (83)

A placebo or test substance was administered IP for three consecutive days to immature female mice weighing 13 ± 1 g. Animals were scarified 24 hours after the final dose and the wet weight of the uterus of each animal was determined. An increase in uterine wet weight of 50 percent or more (≥50%) compared with the placebo group of animals is shown in parentheses, indicating a possible estrogen agonistic activity. Note: the value in the estradiol group was compared with the initial placebo control orally with 2% Tween 80 (wet weight of the uterus was 16.5 mg).

Thus, as described above, a dietary composition or supplement is obtained that includes one or more processed products obtained from an Indian mulberry plant, the scientific name of which is Morinda citrifolia L., and used to provide estrogenic effects in the human body.

Inhibition of estrogen production

The following describes the method and its signs and composition of aromatase inhibition both for treating and preventing the growth of mammalian cancer cells, as well as for decreasing the production of estrogen in the mammal's body, which promotes the growth of estrogen-dependent malignant tumors, each by prophylactic administration of a biologically active supplement composition, including, at least one form of the processed product of Morinda citrifolia.

Embodiments of the present invention relate to aromatase inhibitors, a dietary supplement composition, or an aromatase inhibitor, or a composition that acts on estrogen-dependent cancer cells, which includes Morinda citrifolia, an Indian mulberry plant. Morinda citrifolia is formulated as a dietary supplement along with various carriers or suitable for in vivo treatment of a patient. For example, the inhibitor can be taken orally, injected, administered intravenously, or absorbed in any other suitable way as prescribed.

In one representative embodiment, the dietary supplement composition of the present invention includes one or more processed products of Morinda citrifolia, in an amount of between 0.01 and 100 percent by weight, preferably between 0.01 and 95 percent by weight. Several embodiments of the formulations are presented below. However, they are presented only as examples, and the specialist in this field it is clear that can be obtained in other formulations or compositions, including the processing product of Morinda citrifolia.

The Morinda citrifolia processing product includes at least one of the active ingredients in the dietary supplement or contains one or more active ingredients, such as quercetin and rutin, and others, to effect aromatase inhibition and reduce and control estrogen production by inhibiting binding estrogen receptors with estrogen, as well as for the destruction of estrogen-dependent cancer cells, in particular, estrogen-dependent cancer cells at an early stage.

The active ingredients in the Morinda citrifolia processing product can be extracted using various alcohols or alcohol solutions, for example methanol, ethanol and ethyl acetate, or other alcohol derivatives, using any processes known in the art. In the final composition or composition, the active ingredients quercetin and rutin are present in amounts of from 0.01 to 10 percent by weight. These amounts can also be concentrated in higher concentrations, in which they are present in amounts ranging from 10 to 100 percent.

The processing product of Morinda citrifolia may be mixed with various other ingredients to produce various compositions, for example, a dietary supplement, a local skin composition, or others. The composition of the biologically active additive uses any ingredients that are safe for administration to the body of a mammal, in particular humans, and can exist in various forms, for example, in the form of liquids, tablets, troches, aqueous or oily solutions, dispersed powders or granules, emulsions, syrups , elixirs and the like. Moreover, since the composition of the dietary supplement is preferably used orally, it may contain one or more substances selected from the group including sweeteners, flavorings, colorants, preservatives and other medicinal substances, as prescribed.

The composition for topical application of the composition also uses ingredients that are safe for assimilation by the mammalian body and can exist in various forms, for example, in the form of gels, lotions, creams, ointments, and the like, each containing one or more carriers. Ingredients for systemically administered formulations (e.g., intravenously) may also include any known in the art.

The present invention also characterizes a method of administering a dietary supplement composition to a mammal to inhibit aromatase, as well as to reduce and / or regulate estrogen production. In one typical embodiment, the method includes the following steps (a) formulating a dietary supplement composition, comprising in part a Morinda citrifolia processed product, present in an amount of between 0.01 and 95 percent by weight, where the composition also includes a carrier, for example, water or distilled water , and may also include other natural or artificial ingredients; (b) administering a dietary supplement composition to a mammal, such that the Morinda citrifolia processed product is adequately absorbed; (c) repeating the above steps as often as necessary to provide an effective amount of the processed product to inhibit aromatase enzymes whose function is to convert androgens to estrogens, inhibit the binding of receptors to estrogen, and / or reduce and / or regulate estrogen production.

The step of administering a biologically active supplement composition to a mammal preferably includes oral administration of the composition. In particular, the composition of the dietary supplement may be a liquid, gel, solid or other form that will allow the composition to be rapidly absorbed and concentrated in the large intestine. It is important to note that the stage of administration of a dietary supplement composition should be carried out in an effective manner, so that the highest concentration of the dietary supplement composition is absorbed in the tissues and cells. In order for the composition of a biologically active additive to exert an effect, it must be adequately absorbed. After adequate assimilation, the composition may then begin to act by inhibiting aromatase, inhibiting estrogen binding to receptors and reducing the amount of estrogen produced.

In another embodiment, the step of administering a dietary supplement composition may include injecting the composition using an intravenous pump. This technology is advantageous because it will allow the composition to be localized in the area where the composition will have the greatest effectiveness, or in the area where the highest concentration of the composition of a dietary supplement will be provided, for example, in the area of the breast in a patient with breast cancer. In one typical embodiment, the dietary supplement composition is administered by consuming from 1 teaspoon to 2 ounces, preferably 2 ounces, the dietary supplement composition every two hours daily, or at least twice a day for a long period of time. Also, the composition of the dietary supplement should be taken on an empty stomach, which means a period of time at least two hours before a meal or liquid. As a result, the composition of a dietary supplement can actively inhibit aromatase, thus positively affecting estrogen-dependent cancer cells and inhibiting their growth in the body. Of course, it will be understood by one of skill in the art that the amount of composition and frequency of use may vary among different individuals.

The following tables illustrate or represent some preferred formulations or compositions contemplated in accordance with the present invention. As indicated, they are intended only to illustrate embodiments of the invention and do not limit it in any way.

Composition One Ingredients Percentage by Weight Juice puree or Morinda citrifolia juice one hundred% Composition Two Ingredients Percentage by Weight Morinda citrifolia juice 85-99.9% Water 0.1-15% Composition Three Ingredients Percentage by Weight Morinda citrifolia juice 85-99.9% juice of fruits other than Morinda citrifolia 0.1-15% Composition Four Ingredients Percentage by Weight Morinda citrifolia juice 50-90% Water 0.1-49.9% juice of fruits other than Morinda citrifolia 0.1-30% Composition Five Ingredients Percentage by Weight Morinda citrifolia juice puree 85-99.9% Water 0.1-15% Composition Six Ingredients Percentage by Weight Morinda citrifolia juice puree 85-99.9% juice of fruits other than Morinda citrifolia 0.1-15% Composition Seven Ingredients Percentage by Weight Morinda citrifolia juice puree 50-90% Water 0.1-49.9% juice of fruits other than Morinda citrifolia
Composition Eight 0.1-30% Ingredients Percentage by Weight dietary fiber Morinda citrifolia 0.1-30% Water 1-98.9% juice of fruits other than Morinda citrifolia 1-99.9% Composition Nine Ingredients
dietary fiber Morinda citrifolia The percentage by weight of 0.1-30% Water 1-98.9% Juice or Juice Puree Morinda citrifolia 1-99.9% Composition Ten Ingredients
Morinda citrifolia oil The percentage by weight of 0.1-30% carrier medium 70-98.9% other ingredients 1-95% Composition Eleven Ingredients Percentage by Weight product Morinda citrifolia 10-80% carrier medium 20-90% Composition Twelve Ingredients Percentage by Weight product Morinda citrifolia 5-80% carrier medium 20-95% Composition Thirteen Ingredients Percentage by Weight Morinda citrifolia oil or oil extract 0.1-20% carrier medium 20-90% Composition Fourteen Ingredients for Juice Puree or Morinda Citrifolia Juice The percentage by weight of 0.1-80% Morinda citrifolia oil 0.1-20% carrier medium 20-90% Composition Fifteen Ingredients Percentage by Weight Morinda citrifolia juice concentrate or juice concentrate one hundred% Composition Sixteen Ingredients Percentage by Weight juice concentrate or puree juice concentrate Morinda citrifolia 85-99.9% Water 0.1-15%

As indicated in one typical embodiment, the present invention characterizes a method of administering a composition or composition for internal use to inhibit aromatase, reduce / regulate estrogen production, inhibit estrogen binding to receptors, and treat, prevent, inhibit, destroy and completely alter the effects of estrogen-dependent tumors and growth of malignant cells within the area of the malignant tumor, for example in the area of the mammary gland. Essentially, this method includes the introduction of a composition for internal use in the body of a mammal affected by cancer cells. Here, the use of several embodiments of an internal composition comprising various ingredients, each embodiment includes one or more forms of a Morinda citrifolia processed product, as explained and shown here, and a carrier agent or medium.

In one preferred method, aromatase or aromatase enzymes are inhibited, an effect on estrogen-dependent cancer is prevented, the growth of cancer cells is prevented, destroyed and / or completely changed by assigning at least one ounce (1) of one of the compounds from Composition One to Composition on an empty stomach in the morning The sixteen described above, and at least one (1) ounce on an empty stomach in the evening, immediately before bedtime. In one example, which is not a limitation, the medicinal Morinda citrifolia is processed into Tahitian Noni® juice manufactured by Morinda, Inc., Orem, Utah.

In one typical embodiment, the composition for internal use includes the following ingredients: a Morinda citrifolia processed product, present in an amount of between 10 and 80 percent by weight; and a carrier medium, present in an amount between 20 and 90 percent by weight.

In this embodiment, the Morinda citrifolia processed product may include the juice of one or more processed Morinda citrifolia fruits, pureed juice, processed Morinda citrifolia, processed Morinda citrifolia fiber, and / or Morinda citrifolia oil extract.

In another typical embodiment, the composition for internal use contains the following ingredients: juice or juice from processed Morinda citrifolia fruits, present in an amount by weight between 0.1 and 80 percent; processed Morinda citrifolia oil, present in an amount by weight between 0.1 and 20 percent; and a carrier medium, presented in an amount by weight between 20 and 90 percent. Juice puree or fruit juice of Morinda citrifolia can also be formulated with processed fibers of processed Morinda citrifolia presented in similar concentrations.

In accordance with the present invention, private methods of administering the composition for internal use may include any method of actually administering the composition for internal use in a mammal, for the purposes described herein. Although there are many private methods, the present invention determines that the composition for internal use can be administered intravenously, transdermally, orally or systemically. Regardless of which method is used, the main thing is that the composition is completely absorbed, so that the composition for internal use, in particular Morinda citrifolia and other active ingredients, can effectively inhibit aromatase and act on estrogen-dependent cancer, thereby contributing to the reduction and subsequent inhibiting and preventing such cancer, as well as estrogen-dependent cancer cells at any early stage, can be destroyed.

The carrier medium set forth in the aforementioned Formulations may include any ingredient that can be introduced into the body of a mammal and which is also capable of providing a carrier medium for the Morinda citrifolia processing product. Certain carrier formulations are known in the art and are not described in detail here. As indicated, the purpose of the carrier medium is to ensure the delivery of the Morinda citrifolia processing product as part of an internal composition that can be introduced into the body.

The following examples explain and present the prophylactic and therapeutic effects of Morinda citrifolia processed products on aromatase and estrogen-dependent cancer cells, as well as the prophylactic and therapeutic effects of Morinda citrifolia on the proliferation or metastasis of these cancer cells. These examples are not provided here as a limitation, but as an illustration of the benefits and benefits, as well as therapeutic effects, of Morinda citrifolia products.

Example 1

Current well-known treatments available to women with breast cancer in the postmenopausal period include treatment regimens aimed at either blocking or inhibiting estrogen receptors or blocking the effects of aromatase. However, these treatments are not able to combine both actions. Recent experiments have been performed using in vitro bioassays to evaluate the inhibition of aromatase enzyme and the radioligand binding activity of Morinda citrifolia in the form of Tahitian Noni® juice puree.

In this experiment, recombinant human cells were used as a source of estrogen receptors ERα and ERβ. Each of the positive control enzymes, diethylstilbestrol aromatase and СYР450 2С19, were of human origin.

First, 1% Tahitian Noni® juice puree was examined. The results of this test showed that the active ingredient Morinda citrifolia caused or induced 89% inhibition of CYP450 2C19 enzyme receptor aromatase inhibition, 99% inhibition of estrogen-alpha receptor aromatase inhibition of the enzyme, and 102% inhibition of estrogen-beta receptor aromatase inhibition of the enzyme. These results obviously suggest that the used Morinda citrifolia juice puree at the used concentration had a significant effect on the inhibition of aromatase and estrogen receptors, which inhibition can be compared with modern known treatments.

Moreover, it was found that Morinda citrifolia inhibited 81% 1A2, 89% 2C19, 81% 2C9, 93% 2D6, and 77% 3A4 CYP450 enzymes.

Thus, as discussed herein, embodiments of the present invention encompass estrogenic activity in the human body. More specifically, the present invention relates to the use of a biologically active composition or additive for selectively inhibiting estrogen production and providing estrogenic effects in the human body, where the composition is formulated from one or more plant processing products Indian mulberry, the scientific name of which is Morinda citrifolia L. The present invention can be embodied in other particular forms, without going beyond its essence or basic characteristics. It is believed that the described embodiments are illustrative and not limiting.

Thus, the scope of the invention is determined by the attached claims, and not in accordance with the description presented above. All changes within the meaning and range of equivalents of the claims are encompassed by this invention.

Claims (60)

1. The use of the processing product Morinda citrifolia as a biologically active additive for the selective inhibition of the production of estrogen in the body of a mammal and providing estrogenic effects in the body. 2. The use according to claim 1, where the processing product is one of: (i) Morinda citrifolia fruit juice: (ii) Morinda citrifolia oil extract; (iii) dietary fiber Morinda citrifolia; (iv) Morinda citrifolia juice puree; (v) Morinda citrifolia puree; (vi) Morinda citrifolia fruit juice concentrate; (vii) Morinda citrifolia juice puree concentrate; and (viii) Morinda citrifolia leaf extract. 3. The use according to claim 2, additionally providing a stage that provides the recommended use of a biologically active additive, where the recommended use includes the use of one fluid ounce of a biological supplement per day; drinking more than one fluid ounce of a dietary supplement per day; and consuming less than one fluid ounce of a dietary supplement per day. 4. The use according to claim 3, where the recommended use additionally provides for the use of a dietary supplement before a meal. 5. The use according to claim 1, where the application provides either (i) use, or (ii) transdermal use. 6. The use according to claim 1, further providing for the use of a biologically active additive as an aromatase inhibitor. 7. The use of the extract of processed leaves of Morinda citrifolia in the form of a biologically active additive as an aromatase inhibitor for controlling the production of estrogen in the body of a mammal to selectively inhibit estrogen production and provide estrogenic effects. 8. The use according to claim 7, further providing for the use of the processed extract to provide estrogenic effects in the body. 9. The use according to claim 7, where the processed extract is presented in the form of a cream for the skin. 10. The use according to claim 7, where the recommended application includes the use of one fluid ounce of a dietary supplement per day; drinking more than one fluid ounce of a dietary supplement per day; and consuming less than one fluid ounce of a dietary supplement per day. 11. The use of claim 10, where the recommended use further provides for the use of a dietary supplement before meals. 12. A dietary supplement for inhibiting estrogen production and increasing estrogen levels in humans, where the additive contains a processed product of Morinda citrifolia. 13. The dietary supplement of claim 12, wherein the product is selected from (i) leaves of Morinda citrifolia; and (ii) Morinda citrifolia juice. 14. A method of inhibiting aromatase and aromatase enzymes, the function of which is to convert androgens to estrogens, wherein said method comprises administering to a mammal a composition comprising a processing product of Morinda citrifolia in an amount of about 0.01 to 100% by weight, wherein said processing product of Morinda citrifolia contains the active ingredient quercetin. 15. The method according to 14, where the amount of said quercetin is from about 0.1 to 100 wt.%. 16. The method according to 14, where the specified processing product of Morinda citrifolia is at least one of: (i) Morinda citrifolia fruit juice; (ii) Morinda citrifolia oil extract; (iii) dietary fiber Morinda citrifolia; (iv) Morinda citrifolia juice puree; (v) Morinda citrifolia puree; (vi) Morinda citrifolia fruit juice concentrate; and (vii) Morinda citrifolia juice puree concentrate. 17. The method of claim 14, wherein said Morinda citrifolia processing product further comprises, as an additional active ingredient, rutin, which synergistically inhibits said aromatase together with said quercetin. 18. The method according to 17, where the amount of the specified routine is from about 0.1 to 10 wt.%. 19. The method according to 14, where the specified composition is entered in one of the following ways: (i) oral administration; (ii) transdermal administration to the indicated affected area; (iii) injection into the specified affected area; (iv) intravenously; and (v) systemically. 20. A method of inhibiting aromatase and preventing the formation and growth of estrogen-dependent cancer cells in a mammal, wherein said method comprises the following steps: a step of adding a Morinda citrifolia processing product to the alcohol solution; a step of isolating and extracting the active ingredient of said Morinda citrifolia processing product from said solution; the introduction of the specified extracted active ingredient into the body of a mammal, where the specified extracted active ingredient inhibits, prevents, neutralizes and reverses the effects of these estrogen-dependent cancer cells. 21. The method of claim 20, wherein said Morinda citrifolia processed product comprises at least one of (i) processed fruit Morinda citrifolia fruit juice, and (ii) Morinda citrifolia processed product comprising processed Morinda citrifolia puree. 22. The method according to claim 20, where the specified alcoholic solution is selected from the group comprising essentially methanol, ethanol, ethyl acetate and other alcohol derivatives. 23. The method according to claim 20, where the specified active ingredient is quercetin. 24. The method according to item 23, where the specified active ingredient is rutin, which synergistically inhibits the formation and growth of these estrogen-dependent cancer cells together with the specified quercetin. 25. The method according to claim 20, where the specified stage of the introduction of the specified extracted active ingredient provides for the patient to take two ounces of the food product twice a day on an empty stomach, where the specified food product contains the specified active ingredient obtained from the processing product of Morinda citrifolia. 26. The method of claim 20, wherein said step of administering said extracted active ingredient comprises applying a topical composition to said area, wherein said topical composition comprises said active ingredient obtained from a Morinda citrifolia processed product. 27. A method for inhibiting aromatase and preventing the formation and growth of estrogen-dependent cancer cells in mammals, the method comprises the stage of oral administration in the morning on an empty stomach to the specified mammal at least one ounce of the composition of a dietary supplement containing the processing product of Morinda citrifolia; the stage of oral administration to bedtime on an empty stomach to the specified mammal at least one ounce of the composition of the biologically active additives; and repeating said stages of oral administration daily until said estrogen-dependent cancer cells are destroyed. 28. The method according to item 27, where the specified composition of the biologically active additives contains the juice of processed fruits of Morinda citrifolia, in an amount of about 100 wt.%. 29. The method according to item 27, where the specified composition of the biologically active additives contains; juice of processed fruits of Morinda citrifolia in an amount of from about 85 to 99.9 wt.%; and water in an amount of from about 0.1 to 15 wt.%. 30. The method according to item 27, where the specified composition of the biologically active additives contains juice of processed fruits of Morinda citrifolia in an amount of from about 85 to 99.9 wt.%; and juices of fruits other than Morinda citrifolia, in an amount of from about 0.1 to 15 wt.%. 31. The method according to item 27, where the specified composition of a biologically active additive contains juice of processed fruits of Morinda citrifolia in an amount of from about 50 to 90 wt.%; water in an amount of from about 0.1 to 49.9 wt.%; and juices of fruits other than Morinda citrifolia, in an amount of from about 0.1 to 30 wt.%. 32. The method according to item 27, where the specified composition of the dietary supplement contains juice puree from processed fruits of Morinda citrifolia in an amount of about 100 wt.%. 33. The method according to item 27, where the specified composition of a biologically active additive contains juice from processed Morinda citrifolia fruits in an amount of from about 85 to 99.9% by weight; and water in an amount of from about 0.1 to 15 wt.%. 34. The method according to item 27, where the specified composition of a biologically active additive contains juice from processed Morinda citrifolia fruits in an amount of from about 85 to 99.9% by weight; and juices of fruits other than Morinda citrifolia in an amount of from about 0.1 to 15 wt.%. 35. The method according to item 27, where the specified composition of a biologically active additive contains juice puree from processed fruits of Morinda citrifolia in an amount of from about 50 to 90 wt.%; and water in an amount of from about 0.1 to 49.9 wt.%; and juices of fruits other than Morinda citrifolia, in an amount of from about 0.1 to 30 wt.%. 36. The method according to item 27, where the specified stage of oral administration includes oral administration of two ounces of the specified composition of biologically active additives. 37. A method of regulating estrogen production and inhibiting the ability of estrogen receptors to bind to estrogen, wherein said method comprises the following steps: the stage of oral administration in the morning on an empty stomach at least one ounce of the composition of a biologically active additive containing the processing product of Morinda citrifolia; and the stage of oral administration in the evening before going to bed at least one ounce of the specified composition of biologically active additives. 38. The method according to clause 37, where the specified composition of the biologically active additives contains the juice of processed fruits of Morinda citrifolia in an amount of about 100 wt.%. 39. The method according to clause 37, where the specified composition of a biologically active additive contains juice of processed fruits of Morinda citrifolia in an amount of from about 85 to 99.9 wt.%; and water in an amount of from about 0.1 to 15 wt.%. 40. The method according to clause 37, where the specified composition of a biologically active additive contains juice of processed fruits of Morinda citrifolia in an amount of from about 85 to 99.9 wt.%; and juices of fruits other than Morinda citrifolia in an amount of from about 0.1 to 15 wt.%. 41. The method according to clause 37, where the specified composition of a biologically active additive contains juice of processed fruits of Morinda citrifolia in an amount of from about 50 to 90 wt.%; water in an amount of from about 0.1 to 49.9 wt.%; and juices of fruits other than Morinda citrifolia, in an amount of from about 0.1 to 30 wt.%. 42. The method according to clause 37, where the specified composition of the biologically active additives contains juice puree processed fruits Morinda citrifolia in an amount of about 100 wt.%. 43. The method according to clause 37, where the specified composition of a biologically active additive contains juice puree of processed fruits of Morinda citrifolia in an amount of from about 85 to 99.9 wt.%; and water in an amount of from about 0.1 to 15 wt.%. 44. The method according to clause 37, where the specified composition of a biologically active additive contains juice puree of processed fruits of Morinda citrifolia in an amount of from about 85 to 99.9 wt.%; and juices of fruits other than Morinda citrifolia in an amount of from about 0.1 to 15 wt.%. 45. The method according to clause 37, where the specified composition of a biologically active additive contains juice puree of processed fruits of Morinda citrifolia in an amount of from about 50 to 90 wt.%; water, in an amount of from about 0.1 to 49.9 wt.%; and juices of fruits other than Morinda citrifolia, in an amount of from about 0.1 to 30 wt.%. 46. The method according to clause 37, where the specified stage of oral administration provides for oral administration of two ounces of the specified composition of biologically active additives daily twice a day. 47. A method of inhibiting aromatase and the ability of estrogen to bind to estrogen receptors for the treatment, prevention, inhibition, destruction and treatment of estrogen-dependent cancer cells in mammals, wherein said method comprises the following steps: the stage of systemic administration of the composition for internal administration to a mammal, where the specified composition for internal administration contains a processed product of Morinda citrifolia, in an amount of from about 10 to 80 wt.%; and the carrier medium in an amount of from about 20 to 90 wt.%. 48. The method according to clause 47, where the specified processing product of Morinda citrifolia is at least one of: (i) juice of processed fruits of Morinda citrifolia; (ii) Juice puree from processed Morinda citrifolia fruits; and (iii) dietary fiber processed Morinda citrifolia. 49. The method according to clause 47, where the specified stage of internal administration of the composition is selected from the group consisting of intravenous administration, oral administration and injection. 50. A method of inhibiting aromatase and regulating estrogen production, wherein said method comprises the following steps: the stage of introduction of the composition for internal use in the body of a mammal, where the specified composition for internal use contains processing product of Morinda citrifolia, in an amount of from about 5 to 80 wt.%; and the carrier medium, in an amount of from about 20 to 95 wt.%. 51. The method of claim 50, wherein said Morinda citrifolia processing product is selected from the group consisting of processed Morinda citrifolia fruit juice, processed Morinda citrifolia fruit juice, processed Morinda citrifolia fiber, processed Morinda citrifolia oil, and processed Morinda processed oil citrifolia. 52. The method of claim 50, wherein said step of administering the composition for internal use comprises methods selected from the group consisting of intravenous administration, oral administration, transdermal administration and injection. 53. An aromatase inhibitor for treating estrogen-dependent mammalian tumor cells, comprising a dietary supplement composition containing at least one Morinda citrifolia processed product. 54. The aromatase inhibitor according to paragraph 53, where the specified processing product of Morinda citrifolia is at least one of: (i) Morinda citrifolia fruit juice; (ii) Morinda citrifolia juice puree; (iii) Morinda citrifolia juice puree concentrate; (iv) Morinda citrifolia fruit juice concentrate; and (v) dietary fiber Morinda citrifolia. 55. The aromatase inhibitor according to paragraph 53, wherein said Morinda citrifolia processing product of said dietary supplement composition further comprises the active ingredient quercetin, in an amount of about 0.1 to 10% by weight. 56. The aromatase inhibitor of claim 53, wherein the amount of said Morinda citrifolia processing product is from about 0.01 to 100% by weight. 57. The aromatase inhibitor of claim 55, wherein said Morinda citrifolia processing product also contains rutin as an additional active ingredient that acts synergistically with quercetin in the treatment of migraine-like headaches and related symptoms. 58. The aromatase inhibitor according to clause 57, where the amount of the specified routine is from about 0.1 to 10 wt.%. 59. The aromatase inhibitor according to paragraph 53, wherein said dietary supplement composition (i) is administered orally, (ii) is applied transdermally to said affected area, (iii) is administered intravenously or (iv) systemically. 60. A method of regulating the production of estrogen in the body of a mammal for therapeutic effects on estrogen-dependent tumors, wherein said method comprises the following steps: a stage of systemically administering a composition for internal use to a mammalian body, wherein said composition for internal use contains a Morinda citrifolia processed product in an amount from about 0.1 to 100 wt.%.

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