GR1009416B - Solution acting against masculine alopecia and benign prostate hyperplasia - Google Patents

Abstract

Novelty: a therapeutic formula acting against hair loss and benign prostate hyperplasia is disclosed. Content: the invented formula contains the following mother tincture extracts: 1) sabal serrulate antagonizing the action of cholesterol by reducing it; 2) Agropyron repens; 3) solidago virgaurea exhibiting diuretic action for better detoxification.

Description

DESCRIPTION

"Solution for the treatment of male alopecia and

benign prostatic hyperplasia"

The invention refers to an oral alcoholic solution which contains

extract of mother tinctures of three herbs.

There are already several products on the market aimed at

treatment of androgenetic alopecia, which are based

the pharmacological action of Minoxidil, Finasteride and

Dutasterides.

The most common treatment regimen is the combination,

for external use, of Minoxidil, applied locally for the

absorption of it, in the form of a solution (lotion), alongside the

administration of the internal use of Finasteride, in oral form

pharmaceutical preparation (tablet).

Minoxidil is applied externally, for the reason that it is a

very powerful vasodilator, so its internal use will

could cause a severe clinical case of hypotension.

The mechanism of action of these substances concerns the inhibition of the enzyme

5α-reductase, i.e. they inhibit the reaction of its conversion

of testosterone to (5a-DHT), viz

5α-dihydrotestosterone, accelerating, in this way, the

activity of the aromatase enzyme, due to competitive metabolic

syndrome, according to the following reactions:

In particular, aromatase is the key enzyme in the biosynthesis of

of estrogen, since it catalyzes the reaction in which, from

estradiol (female hormone) is synthesized from testosterone.

However, this particular treatment carries many risks, for the following reasons:

(I) estrogens are neurosteroidal, positive, allosteric modulators of γ-aminobutyric acid (GABA), thus leading to states of depression, anxiety or sexual dysfunctions.

(II) estrogens are hydrophobic compounds of high molecular weight.

Microtubules, i.e. flexible, unstable polysaccharides, are then joined in the plasma, resulting in the formation of saturated complexes of long polysaccharide chain organic compounds, which cannot be eliminated through the detoxification pathways, consequently being stored as toxins, thus causing high levels of toxicity.

(III) Finally, long-term treatment with the above drugs leads to a large increase in estrogen, which translates into stimulation of the action of aldosterone, which means an increase in fluid retention, due to the production of the antidiuretic hormone vasopressin (Vasopressina: ADH)

In this case, the most common diuretics used in current treatment regimens are loop of Henle diuretics, such as ethacrynic acid or sulfonamides. It refers to O-chlorobenzenesulfonamide compounds, of the furosemide type, which is found as an active element in the composition of most commercial pharmaceutical preparations.

The pharmacological action of the above compounds is related to the inhibition of the transport of sodium ions (Na+) in the anodic part of the loop of Henle and in the tubules.

Consequently, the inhibition of reabsorption of sodium ions (Na+) leads to hypokalemia, due to the increased excretion of potassium ions (k+) which, at the level of the distal tubules, are no longer exchanged, under the action of aldosterone, with sodium ions (Na+). Therefore, the main side effects of the administration of these diuretics are: hypokalemia, hyperglycemia and hyperuricemia.

The preparation concerning the present invention is advantageous compared to many commercial products.

More specifically, it does not aim to inhibit 5α-reductase, therefore it does not cause an increase in estrogen, due to the enhancement of the aromatase enzyme activity, according to the syndrome of competitive metabolism, with consequent stimulation of the GABA activity.

Specifically, instead of Finasteride and Minoxidil, this preparation uses phytosterols or plant sterols, which are contained in the mother tincture of the herb Sabal serrulatta or Serenoa repens. That is, phytosterols are compounds with a similar chemical structure to cholesterol, with which they compete with its absorption by intestinal cells, reducing it. A decrease in the absorption of intestinal cholesterol, of animal origin, indicates the appearance of antiandrogenic peripheral characteristics.

Therefore, phytosterols do not cause competitive inhibition of steroid hormones or their enzymes.

Then, to avoid potential risks due to fluid retention due to the low rate of absorption of phytosterols, the preparation contains, instead of diuretics of the loop of Henle, i.e. thiazines, non-electrolytic osmosis saccharides, which are contained in the mother tinctures of the herbs: Agropyron repens and Solidago virgaurea.

The present invention relates to an oral alcoholic solution, which contains an extract of mother tinctures of the three following herbs:

Sabal serrulata, Agropyron repens and Solidago virgaurea, with the following quantitative ratio: per 100 ml contains Sabal serrulata 40% by weight, Agropyron repens 30% by weight, and Solidago virgaurea 30% by weight. Suggested dosage: 3ml, before meals, three times a day.

This specific composition aims to treat hair loss (alopecia) and to treat benign prostatic hyperplasia.

More specifically, the herb Sabal serrulata or Serenoa repens or Saw palmetto belongs to the plant family:

Arecaceae / Palmaceae.

The useful part of the plant for the production of the extract is the ripe palm fruit.

Its chemical composition is as follows:

The total fraction of acids, which can be obtained from the lipid extracts of Sabal serrulata, consists mainly of free fatty acids and of fatty acids that are products of external hydrolysis:

A: Oleic acid (21-25%)

B: Myristic acid (11-12%)

C: Palmitic acid (10-11%) and palmitoleic acid

D: Stearic acid (1.5-2.5%)

E: Linoleic acid (1.8-3%) and linolenic acid

F. Arachidonic acid (0.05-0.20%) and ,

G:eicosenoic acid (0.01-0.2%)

The extract also contains additional substances, such as:

H: non-saponoids

I: esters

J: sterols, and

K: aliphatic alcohols.

Therefore, the liposterol extract contains a mixture of saturated or unsaturated hydrocarbons (alkanes, alkenes), phytosterols and anthranilic acid.

Phytosterols or plant sterols, such as campesterol, β-sitosterol and stigmasterol, belong to the triterpene family in free or esterified form. Their chemical structure, as found below and their composition, are analogous to cholesterol, which is why they compete with it in the intestine, reducing the rate of its absorption in a dose-dependent manner.

They are then transported to the liver, via plasma chylomicrons, like cholesterol, and through this mechanism, reduce its hepatic uptake, thereby causing the liver cell to increase its uptake of LDL, through its receptors.

In particular, the percentage of phytosterols absorbed by the liver cells undergoes oxidation, through the enzyme catalyst, located in the mitochondria: cytochrome P450scc, with the production of acidic liquids, which are excreted in the duodenum with bile, to facilitate the digestion process and the absorption of lipids, as well as fat-soluble vitamins.

That is, they condense with sulfur amines or polysaccharides forming sodium (Na+) or potassium (k+) sulfate salts, which are finally excreted through the urinary system, thus allowing lipolysis, while at the same time exerting an antibacterial effect as antagonists of Gram (-) bacterial flora .

The rest of the phytosterols that were not absorbed, returns, through the carriers that are transporters of the cell membrane, back to the intestinal lumen, where it is excreted, penetrates the entire colon and finally ends up in the rectum, where it is eliminated with the feces through defecation.

The final conclusion is that phytosterols, as a reference for their pharmacokinetics, have an advantage compared to other compounds of a similar chemical structure, such as cholesterol, which compete with cellular absorption (hepatic or intestinal), due to their excellent elimination, as a final result, from the body .

Phytosterols present similar advantages in terms of their pharmacodynamics.

More specifically, they have an excellent pharmacological effect against hair loss (treatment of alopecia) and against prostatic benign hyperplasia.

They exert anti-androgenic peripheral action, i.e. they act as hormone inhibitors - antagonists, but without affecting the axis: hypothalamus.

Therefore there is no significant hormonal disruption, such as obesity as an extreme example, due to an increase in estrogens that are stimulators of GABA (γ-aminobutyric acid) receptor action, thus leading to depression, anxiety or sexual dysfunction, as could occur in the case of a high concentration of cholesterol, which is explained next, analyzing its mechanism of action.

Another advantage of phytosterols is that they reduce the concentration of neurosteroid hormones, creating carbon bonds with them to form compounds that can be excreted through the urinary tract.

Therefore, they also reduce the action of male hormones in the cellular tissue of the hair follicles (alopecia) and in the cellular tissue of the prostate gland (prostate).

Finally, they accelerate cell apoptosis (programmed cell death) by reducing the number of cells, thus reducing the volume of the prostate, to deal with benign hyperplasia.

On the contrary, the disadvantages of cholesterol are as follows:

It is a sterol of animal origin, similar in structure to phytosterols, which, through the catalyst enzyme: cytochrome P450, undergoes hydrolysis and is converted into Pregnenolone: a hydrophobic compound and an active endogenous steroid.

Pregnenolone is the metabolic precursor of steroid hormone biosynthesis:

progestogens, androgens, estrogens, glucocorticoids and saltocorticoids.

Pregnenolone and its 3β-sulfate derivative, DHEA (dihydroepiandrosterone) and its sulfate derivative and finally progesterone constitute the main class of neurosteroid hormones.

The conversion of cholesterol to pregnenolone and the biosynthesis of steroid hormones are illustrated in figure 1.

Neurosteroid hormones affect the function of brain synapses, where they are found in high concentrations and where they are synthesized through hydrolysis reactions, which are catalyzed by the mitochondrial enzyme: cytochrome P450.

Cytochrome P450 also catalyzes the conversion of cholesterol to pregnenolone, it is located in the mitochondria and is controlled by the adrenal glands, but mainly by the hormones of the anterior pituitary, such as luteinizing hormone and follicolostimolante hormone as well.

However, hydrophobic steroid hormones such as:

pregnenolone, DHEA and progesterone, are positive allosteric modulators of GABA at GABAA receptors, i.e. they are stimulators of GABA, leading to symptoms of anxiety, depression or sexual dysfunction, as mentioned above.

Also, they form compounds with the microtubules, with carbon bonds, thus creating long-chain saturated polysaccharides, which are not excreted through the urinary system.

In contrast, hydrophilic steroid hormones, such as their sulfate derivatives, for example pregnenolone sulfate, are negative allosteric modulators of GABA (γ-aminobutyric acid).

They also do not join the microtubules and finally, they activate the dynamic ion channel of the M3 receptor in hepatocytes and pancreatic islets, thus causing the entry of calcium (Ca++) and the release of insulin. They are excreted through the urinary tract.

Therefore, only a small percentage of cholesterol is eliminated from our body, while the larger percentage remains saturated, in the form of organic compounds of high molecular weight and long chain.

However, a normal excretory system, such as the kidneys, is deficient or blocked when another organic vital system is deficient or when a treatment, intended for the particular individual, according to the patient's history, fails to produce the desired results with, on the contrary aggravation and development of a new problem, due to trophic metabolic abnormalities.

It is therefore necessary to stimulate these organs of the excretory functional system, namely the kidneys, using medication without organic tropism or physiological interactions.

This technique reflects the dynamism of the therapeutic method, which consists in stimulating the organs of excretory function.

This leads, in a sense, to the opening of channels, which will cause toxins to be released to be excreted from the body.

Therefore, the therapeutic regimen aimed at administering the specific oral solution of the present invention includes the synergistic action of two more herbs:

Agropyron repens and Solidago virgaurea, which act as non-electrolytic, osmotic diuretics.

Specifically, Agropyron repens or Gramigna, i.e. grass, belongs to the plant family: Poaceae.

For the preparation of the extract, the roots are used as a mother tincture and the daily dosage of the herb should not exceed 6 to 9 grams, accompanied by water to facilitate diuresis.

Its chemical composition is as follows:

A: Carbohydrates (10%), such as glucose, fructose, inositol, mannitol, pectin, tricitin and mucus.

B: Essential oil containing 95% agropyrene as an active ingredient.

C: Flavonoids, such as tricin

D: Saponids, and finally

E: mineral salts, mainly potassium (k+)

Finally, Solidago virgaurea or Verga d'oro, i.e. goldenrod, belongs to the plant family: Asteraceae and the mother tincture of the plant's flowers is used to prepare the extract.

Its chemical composition is as follows:

Contains:

A: Triterpenoid saponins.

B: Glycoside phenols and phenolic acids, such as acido virgureside, accido leiocarposide and chlorogenic acid.

C: Acetylene.

D: Catechin tannins.

Q: Anthocyanins.

F: Flavonoids

G: Hydroxybenzoic compounds. .

H: Inulin.

I: bis-desmosidic acid esters

J: soluble polysaccharides

K: diterpenes and

L: essential oil.

Agropyron repens and Solidago virgaurea are diuretic herbs with similar and complementary action.

They increase the production of urine, without causing an increase in the excretion of electrolytes.

That is, they dilate the glomerular arterioles by increasing their filtration rate, and consequently increasing the excretion, from the kidneys, of sodium ions Na+ (natriuresis) and water.

Therefore, they cause a reduction in the volume of the extracellular fluid, which is responsible for any presence of peripheral edema or hypertension, thus ensuring balance and homeostasis.

The increase in urine production (increased diuresis) also contributes to the increase in the elimination of metabolic products, mainly nitrogenous, derived from the breakdown of protein substances, such as urea, uric acid or creatinine, as well as foreign substances, such as drugs or their metabolites, which enter the body voluntarily or without the will of the patient.

Its pharmacokinetic action is superior to thiazines (the most common diuretics), for the reason that they are non-electrolyte diuretics, with reduced caloric intake, i.e. they are anti-aldosterones, GABA inhibitors.

Therefore, there is no risk of lack of potassium (k+) in cases of cardiac dysfunction or kidney failure, since they contain saccharides, such as fructose and inulin, which, during their filtration by the glomeruli, do not undergo appreciable reabsorption due to the effect of osmosis from the cell tubes. As a result, water is reabsorbed, increasing urine production.

The phenomenon of osmosis is illustrated in Figure 2.

Another category of active substances that contribute to the excellent diuretic effect of the herbs Agropyron repens and Solidago virgaurea are the glycoside phenols, of which approximately 65% are excreted in the urine, regardless of the form of the pharmaceutical preparation in which they are contained.

Figure 3 illustrates the steps in the pharmacokinetics of glycosidic phenols.

More specifically, the glycosidic phenol consists of:

A: organic section (saccharide) and

B: inorganic, non-saccharide part, called: Aglycone, joined together by hydrophilic or water-soluble bonds.

The glycosidic phenol is hydrolyzed in the intestinal lumen resulting in the production of a diphenol compound (polyphenols), which undergoes, through cytochrome P450, direct oxidation to hydroquinone.

Then hydroquinone, through the plasma, is converted by the liver cells into a conjugated compound of sulphide glucuronide (glucosinolatte) in the form of a volatile oil, which, through enzymatic hydrolysis in the urine (pH > 8), releases hydroquinone again.

Free hydroquinone exerts a strong antiseptic and antimicrobial effect.

The biosynthesis of free hydroquinone is described according to the following reaction:

Therefore, herbs containing sulfur glucuronides reduce plasma cholesterol levels and accelerate the elimination of toxins.

Complementary substances, which synergistically ensure the good diuretic effect of the herbs: Argopyron repens and Solidago virgaurea, are:

A: Agropyrene in essential oil

B: the silicon salts, which maintain the elasticity of the connective tissues in the walls of the urinary tract.

C: Triticine and potassium salts (k+) as natural diuretics and finally, D: Inositol, which, in addition to its detoxifying effect, also regulates the concentration levels of calcium (Ca++), thus preventing the accumulation of kidney stones, due to increased concentration (high levels) of calcium oxalate.

Pharmacodynamically, the herbs: Agropyron and Solidago, can give the maximum therapeutic effect when the environmental conditions of the urine have an acidic pH, so it is a necessary condition that they be administered with a simultaneous intake of water, in order to maintain stable the values of the alkaline environment of the urine.

Finally, the hydrolysis products of the conjugated compounds of the herbs exert a great antiseptic and antimicrobial effect against bacteria such as:

A: Escherichia coli

B: Staphylococcus aureus

C: Bacillus subtilis

D: Mycobacterium smegmatis,

and also enhance the action of lactam antibiotics in cases of resistant colonies of Staphylococcus aureus.

Claims (3)

1. Preparation for the treatment of male alopecia and benign prostatic hyperplasia, based on the administration of an alcoholic solution, which is characterized by an extract of mother tinctures of three different herbs. 2. According to the main claim, the extract consists of the mother tinctures of Sabal serrulaia, Agropyron repens and Solidago virgaurea. 3. According to the claims, the present preparation is a form of therapeutic treatment against hair loss, based on a combination of its administration both internally (oral administration) and externally (local applications), since it exerts the same mechanism of action on the hair follicles.