ES2577054A1 - Use of a derivative or extract of plants from the gender carpobrotus to prepare a vasoconstricting composition (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

Use of a derivative or an extract of plants of the genus carpobrotus to prepare a vasoconstrictor composition. Use of at least one plant of the genus carpobrotus to prepare a vasoconstrictive composition for the treatment and/or prevention of diseases or symptoms related to the dilation of vascular tissues. (Machine-translation by Google Translate, not legally binding)

Description

USE OF A DERIVATIVE OR EXTRACT OF CARPOBROTUS GENDER PLANTS TO PREPARE A VASOCONSTRICTORA COMPOSITION

DESCRIPTION

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Technical field

The present invention belongs to the field of treatment and / or prevention of diseases and / or symptoms related to vascular tissue dilation. In particular, it refers to a composition comprising derivatives or extracts of at least one plant of the genus Carpobrotus and its use for the treatment and / or prevention of diseases or symptoms related to vascular tissue dilation.

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State of the art prior to the invention

The vasodilation phenomenon is defined as the process of dilation of the blood vessels by relaxing the smooth muscles of the vessels, causing the increase in diameter of a blood vessel either an artery or vein. This results in a greater volume of blood inside the vessel but less internal pressure. This phenomenon of widening that occurs in both veins and arteries is aimed at making the blood flow more smoothly.

The causes that cause this phenomenon in the circulatory system are very diverse, giving rise to different clinical conditions or conditions whose treatment has been studied in many fields of Medicine and Pharmacy.

These conditions can be included within the field of diseases in the digestive, respiratory, dermatological, etc., so it is often very difficult to find a treatment that suits the condition, treating the associated pain and improving the condition overall of the patient in an effective way.

A particular case of this type of conditions related to the digestive system but whose cause is in the circulatory system are hemorrhoids. 35

Hemorrhoidal disease or more commonly known as hemorrhoids, are inflamed veins in the anus or lower rectum. They are created by inflammation of the tissues in the anal cavernous bodies. This occurs primarily in situations where this area is subjected to constant pressure, for example, when a subject suffers constipation (caused by various causes), or when it is necessary to exert a lot of force when defecating. This pressure causes the veins and anal tissues to swell.

Currently, the treatments that are usually applied for this type of pathology vary depending on the degree of severity of the hemorrhoidal disease. In addition to the intake of a diet rich in fiber, the local use of ointments or suppositories that are combined with anti-inflammatories, soothing and corticosteroids is very common.

Corticosteroid-based treatments can cause many risks due to excessive use, either for long-term use or for using a higher dose than indicated, which results in a series of local or systemic side effects. not wanted:

 Local side effects: Excessive use of corticosteroids can lead to epidermal atrophy, vascular prominence or stretch marks. Stretch marks, which correspond rather to dermal damage, consist of a condition of the structure of collagen and elastic fibers. This condition is frequently associated with excessive use of corticosteroids in anatomical occlusion zones such as the inguinal and axillary areas. To these side effects must also be added the high incidence of local infection (bacterial and fungal) that can cause prolonged use of ultra-potent corticosteroids. 25

 Systemic side effects: Prolonged use of corticosteroids, being a minimum period of two weeks or the use of ultra-potent corticosteroids (Class I) can lead to suprarenal suppression. That is why, although the efficacy of preparations of this class is indisputable, their complications may be comparable to the effects of systemic steroid administration.

In addition, in most cases in which the crisis persists, it is necessary to resort to surgical techniques, whose traumatic effects cause great pain in patients who have to undergo these processes. 35

Another type of pathologies whose clinical picture is related to vasodilation processes are:

 Nasal congestion, which is the sensation of difficulty to the air passage through the

nostrils. This congestion is mainly caused by the vasodilation of the blood vessels of the nasal mucosa.

 Varicose veins or telangiectasia, which occur when the venous return of the superficial veins of the lower extremities is slower. This phenomenon causes an increase in the amount of blood in the lower extremities, leading to vasodilation that in some cases may become chronic. In these cases, these veins are marked on the outer surface of the skin, resulting in an unsightly image, better known as varicose veins or spider veins.

 First degree burns or type A, which are superficial type burns that only affect the epidermis, such as a sunburn. In the first 15 stages, vasoconstriction occurs due to histamine release and then a vasodilation that causes vascular congestion of the superficial capillary plexus that will lead to erythema and the retraction of collagen fibers. This retraction will eventually cause the skin to wrinkle.

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Therefore, taking into account the side effects that derive from the treatments currently known to treat diseases, conditions or pathologies whose origin is based on the dilation of vascular tissues, it would be desirable to have a natural, safer and more natural composition. lacking the side effects described above for use in the treatment of these types of pathologies. 25

In order to be able to find a natural and effective treatment against conditions that are related to the pathological vasodilation phenomenon, the present invention therefore has as its object a composition obtained from plants of the genus Carpobrotus, which is a interesting genus from the medicinal point of view. 30

Since its discovery, this genus has been investigated for different medicinal purposes. Carpobrotus mellei, a native plant of the Cape region in South Africa, was studied for its antimicrobial potential because the native population used it to treat different ailments, such as sore throat, toothache or mouth infections. (Wisura and Glen, 35 1993)

On the other hand, several studies have shown that extracts obtained from Carpobrotus edulis have a strong antibacterial activity (Martins A, Vasas A, Viveiros M, Molnár J, Hohmann J, Amaral L. Antibacterial properties of compounds isolated from Carpobrotus edulis. Int J Antimicrob Agents. 2011 May; 37 (5): 438-44). Using the fingerprint method, flavonoid compounds have been initially identified as rutin, neohesperidine and ferulic acid. In addition, other research projects developed in this field show that extracts obtained from this spice have an immumomodulatory effect on cancer cells, (
Martins A,
Vasas A,
Schelz Z,
Live M,
Molnár J,
Hohmann J,
Amaral L. Constituents of Carpobrotus edulis Inhibit P-Glycoprotein 10 of MDR1-transfected Mouse Lymphoma Cells. 2010. ANTICANCER RESEARCH 30: 829-836) demonstrating its potential for future use in chemotherapeutic treatments. However, to date the vasoconstrictor activity of Carpobrotus edulis has not been described or tested.

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For this, the present application provides different alternatives to use the plant of the genus Carpobrotus, in particular, to manufacture a medicament for treating and preventing diseases associated with dilation of vascular tissues.

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Description of the invention

The main object of the present invention is therefore the use of at least one plant of the genus Carpobrotus to prepare a medicament for the treatment and / or prevention of at least one disease or symptom related to vascular tissue dilation. 25

Within the scope of the present invention, "disease" means the most serious alteration of health. Less serious health disorders are called "conditions" and in turn are understood as "symptom", the manifestation or sign of a disease.

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Therefore, the present invention relates to obtaining a vasoconstrictor composition from the extract or derivative of plants of the genus Carpobrotus and its use to reduce the distention of blood vessels, and can be applied in all those dysfunctions associated with a picture clinical with vasodilation and / or distention of blood tissues. 35

Additionally, the present patent application refers to the manufacture of a composition for application in different parts of the body of an individual for the treatment of diseases or symptoms that are caused by vasodilation of vascular tissues such as:

 In the digestive system, where vasodilation of blood tissues can lead to hemorrhoids, canker sores, intestinal ulcers, etc.

 In the respiratory system, where vasodilation can cause nasal, pulmonary congestion, etc.

 In the superficial circulatory system of epithelial tissue, such as telangiectasia, varicose veins, spider veins, dilated veins in eye bags, etc. 10

Similarly, the vasoconstrictor composition object of the present invention can also be applied in the following clinical conditions:

 In traumatic processes, such as in vasodilation of vascular tissues due to mechanical trauma, burns, etc. fifteen

 In vasodilation processes caused by the use of anesthetics.

Likewise, the object of the present invention is also the use of a derivative or an extract of at least one plant of the genus Carpobrotus to prepare a vasoconstrictor composition that can be used to manufacture a personal hygiene product, cosmetic or food.

"Personal hygiene" is understood in the scope of the present invention, all the actions that are carried out for the care of the individual and "cosmetic products" are understood as the products that are used for
beauty
of the
body. Finally, "food product 25" means, within the scope of the present invention, a product comprising a substance or set of substances with easily digestible nutritional principles that living beings eat or drink. Within the scope of the present invention, cosmetic products are applied in those conditions that are related to an aesthetic aspect of the individual.

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In all the cases indicated above, the present invention is based on the vasoconstrictor effect of the derivative or extract of plants of the genus Carpobrotus that the inventor has been able to demonstrate thanks to a series of tests both in vitro, on human anal sphincter tissue, and in alive, as described in the present application.

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The vasoconstrictor composition of the present invention, whether medicament or personal hygiene product, cosmetic or food comprises between 1% to 99% by weight with respect to the total weight of the final product of a derivative or extract of the plant of the genus Carpobrotus .

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In a preferred embodiment of the invention, the vasoconstrictor composition comprises a plant derivative or extract of the genus Carpobrotus, and is obtained by a process selected from the group consisting of: liquefied, cold pressed or with temperature, maceration, distillate, lyophilized, dried and crushed. In the present invention, derivative is understood as the product obtained from at least one plant of the genus Carpobrotus 10 preferably obtained from the lyophilization, drying or crushing process.

In a preferred embodiment of the present invention, cold pressing is carried out in a temperature range of 0 ° C to 50 ° C, and hot pressing is carried out in a temperature range of 51 ° C to 110 ° C. fifteen

In one embodiment, the plant of the genus Carpobrotus can be applied directly, that is, without mixing it with excipients for the treatment and / or prevention of conditions related to vascular tissue dilation.

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In another preferred embodiment, the vasoconstrictor composition can be presented, according to the procedure that has been used to obtain it, in the form of powder, body oil, poultice, shampoo, eye drops, tablet, cream, solution, emulsion, foam, gel, infusion , injectable, syrup, lyophilized product, lotion, patch, suppository, tonic, ointment, etc. More preferably, the vasoconstrictor composition may be presented in the form of an aqueous, ethyl or oily solution.

More preferably, depending on the disease, condition or symptom that is desired to be treated with the composition of the invention, said composition can be applied with the help of a vaporizer. 30

In a preferred embodiment, the composition described herein manages to reduce the symptoms and the period of hemorrhoidal crisis. In this way, the quality of life of patients is substantially improved, reducing periods of sick leave, as well as the costs of treatment compared to the costs associated with the use of corticosteroids, anti-inflammatories, or surgical interventions.

In order to treat hemorrhoidal crises, the use of the composition of the invention can be applied topically every 12 hours, considerably improving the clinical picture between the first 12 and 36 hours, and a period of reabsorption of the dilated vessels between 3 and 5 days, deadlines that are not achieved with other current methods. 5

In a particular embodiment of the present invention, the vasoconstrictor composition can be obtained in cream form from the stem and leaves of plants of the genus Carpobrotus. This process of obtaining may comprise drying the stem and leaves of at least one Carpobrotus plant at a temperature ranging from 0 ° C to 60 ° C, 10 over a period of 24 to 60 hours to obtain a Carpobrotus derivative, in particular, a Carpobrotus dry product. Then, the dried Carpobrotus product obtained in the previous stage is crushed until a powder thereof is obtained. Said powder is mixed with petroleum jelly in a proportion ranging from 70:30 to 30:70, at a temperature not less than 35 ° C. Subsequently, the mixture obtained in the previous stage is heated to a temperature not less than 95 ° C, maintaining the boil for a time not less than 10 minutes. Finally, once the heating of the mixture is finished, said mixture is decanted and screened twice at a temperature ranging from 40 ° C to 70 ° C, obtaining the vasoconstrictor composition.

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The cream obtained as described above can be applied in the affected areas, preferably every 12 hours, resulting in a decrease in pain and decrease in venous dilation between 12 and 36 hours from the first application, with resorption of dilated vessels 3 to 5 days after the first application.

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With this invention, by using the vasoconstrictor properties of Carpobrotus for the treatment and / or prevention of hemorrhoids, the traumatic effects of surgical interventions and the side effects caused by therapies based on the use of corticosteroids are avoided.

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In another particular embodiment of the present invention, the vasoconstrictor composition can be obtained in the form of body oil by mixing the extract or derivative with pharmaceutically acceptable oils. Preferably, the vasoconstrictor composition described herein comprises between 10% and 70% dry Carpobrotus powder and between 30% and 90% of at least one pharmacologically acceptable oil. 35

This process of obtaining may comprise drying the stem and leaves of at least one plant of the genus Carpobrotus at a temperature ranging from 0 ° C to 60 ° C, for a period of 24 to 60 hours to obtain a Carpobrotus derivative, in particular, a Carpobrotus dry product. Then, the dried Carpobrotus product obtained in the previous stage is crushed until a powder thereof is obtained. Said powder is preferably mixed with coconut oil in a ratio ranging from 30-70: 70-30 at a temperature not less than 35 ° C. Subsequently, the mixture obtained in the previous stage is heated to a temperature not less than 95 ° C, maintaining the boil for a time not less than 10 minutes. Finally, once the heating of the mixture is finished, said mixture is decanted and screened twice at a temperature ranging from 40 ° C to 70 ° C, obtaining the vasoconstrictor composition.

The oil obtained as described above, can be applied in the affected areas, preferably, in 12-hour intervals, resulting in a reduction in the affected capillaries of 60%, maintaining a 2-week treatment, and a 15-week treatment. 80% discoloration 30 days after its first application.

In another particular embodiment of the present invention, the vasoconstrictor composition can be obtained in the form of body oil. This process of obtaining may comprise drying the stem and leaves of Carpobrotus at a temperature ranging from 0 to 60 ° C, 20 for a period of 24 to 60 hours to obtain a dry Carpobrotus product. Then, the dried Carpobrotus product obtained in the previous stage is crushed until a powder thereof is obtained. Said powder, preferably, can be mixed in a proportion of 50% with 25% olive oil and 25% butter in relation to the total weight of the final product, and at a temperature not less than 35 ° C. Subsequently, the mixture obtained in the previous stage is heated to a temperature not less than 95 ° C, maintaining the boil for a time not less than 10 minutes. Finally, once the heating of the mixture is finished, said mixture is decanted and screened twice at a temperature ranging from 40 ° C to 70 ° C, obtaining the vasoconstrictor composition.

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The body oil obtained as described above, can be applied in areas affected by sunburn caused by sun exposure, preferably applied at 12 hour intervals, resulting in a reduction of skin redness and decrease in contact pain. these affected areas.

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The vasoconstrictor composition comprising the plant of the genus Carpobrotus, in particular, the one described in the present application, can be used in the treatment of first and second degree burns, causing decongestion of the affected area and disappearance of pain in a lower period 30 minutes This burn can be covered with breathable dressings for at least 5 days by applying the oil every 12 hours, and a stable healing is observed with disappearance of pain.

In another particular embodiment, the present invention can also be obtained in the form of serum for the treatment of nasal decongestion. In this case, it can be mixed in a proportion of 80% distillate of plant extract of the genus Carpobrotus, obtained in turn from a smoothie of said plant, with 20% of physiological serum. The serum obtained as described above can preferably be applied with the help of a nebulizer every 6 hours, resulting in surprising results. In particular, a decongestant effect can be obtained after the first 3 to 4 minutes.

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Brief Description of the Figures

Figure 1: Photographs showing an RC-29 perfusion chamber and an FR-50 valve (left), and a multi-valve perfusion system VC-66CS (right) are depicted.

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Figure 2: The capacity of arterial contraction in human EAI tissue (n = 3) after incubation with different doses of Carpobrotus extract (CD) is represented. The percentage of contraction was calculated considering the area of the basal arterial lumen as 0% and the area after the contraction by 10mM Histamine as 100%.

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EXAMPLES

In order to contribute to a better understanding of the invention, and in accordance with a practical embodiment thereof, an integral part of this description is accompanied by a series of examples where, with an illustrative and never limiting nature of the invention. In example 1, the result obtained by applying a composition based on plant extracts of the genus Carpobrotus on vascular tissue samples obtained from hemorrhoid patients is compared. In Example 2 a composition based on extract of Carpobrotus plants in the form of an ointment for the treatment of hemorrhoids is applied. In Example 3, a serum-based plant extract composition of Carpobrotus is applied for nasal congestion treatment. In Example 4,

apply a composition based on Carpobrotus plant extract in the form of body oil for the treatment of telangiectasias. Finally, in Example 5, a composition based on Carpobrotus plant extract in the form of body oil is applied for the treatment of burns.

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In all the examples described below, the inventor has been able to test the vasoconstrictor effect of the composition object of the invention in a maximum of 5 volunteers.

Example 1. In vitro study of the vasoconstrictor activity of Carboprotus extract, in tissue samples of internal anal sphincter (EAI) of three patients undergoing surgery for surgical hemorrhoid removal.

A composition rich in Carpobrotus extract was prepared from fresh leaves collected from a private garden (Monte Real Sports Club, Torrent). The leaves were cut and crushed manually with the help of a mortar. fifteen

For the trial, an internal anal sphincter (EAI) sample from three patients (52, 56, 61 years old men), operated by surgical removal of grade IV hemorrhoids was used. The sample was prepared in the two hours following the extraction, removing the remains of blood, including the tissue in 20% gelatin and making individual cuts 20 µm thick using the vibratom (Leica VT1000 S). The sections were kept tempered at 37 ° C in a 5% CO2 incubator, after which they were inspected with the Nikon Eclipse TE200 inverted fluorescence microscope (Nikon, Tokyo, Japan). Among all the cuts, those that presented vessels were selected, with visible light and with the vascular wall and muscle fibers in good condition. These 25 selected cuts were washed with 1 ml of phosphate buffer at 37 ° C for 30 minutes and kept in an incubator with 5% CO2.

The sections were positioned in a specific perfusion chamber for tissue sections (Ref. RC-29; Harvard apparatus) (Figure 1) containing 1 ml of the test medium (RPMI 1640 incubation buffer with 20 mM HEPES, pH 7 ,4). To keep the tissue positioned during the procedure, a “U” shaped platinum piece with 50 µm diameter nylon filaments was applied. In this way, tissue cutting could be perfused with a multi-valve perfusion system (Ref. VC-66CS; Harvard apparatus) and controlled with a valve (Ref. FR-50; Harvard apparatus) that provided a flow of 0 , 5 ml / min for 35

input of the different extract concentrations used (Figure 1). All experiments were performed at 37 ° C.

The perfusion chamber was placed under the 40x objective of the Nikon Eclipse TE200 inverted fluorescence microscope, with a CCD video camera (CoolSNAP HQ2; 5 Photometrics) adapted and connected to MetaFluor software (Molecular Devices, USA) for image analysis.

After an approximate period of 5 minutes to stabilize the vascular tone in the perfusion system with the test medium, the tissue responsiveness was checked with 10 histamine (0.1mM). Preparations that did not respond to histamine were discarded (10%). After washing the histamine, the preparations were rebalanced for 30 min, before applying the compound under study.

A dose-response curve was performed for each subject studied. The concentrations used were of carpobrotus edulis extract 0.1%, 1%, 10%, 50%, 100%. Dilutions of the extract were made in PBS (phosphate buffer saline) at pH 7.4. (Fig. 2).

The studies carried out demonstrated the contractile effect of Carpobrotus extract on the anal sphincter, which translates into a contraction of the surrounding vessels and an improvement in the venous return of the area.

Example 2. Use of stems and leaves of the genus Carpobrotus to make an ointment for the treatment of hemorrhoids.

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For the preparation of the ointment with vasoconstrictor activity from the Carpobrotus extract, the product was taken fresh and kept dried for 48 hours at 50 ° C. Subsequently, it was crushed and mixed with 70:30 roving petroleum jelly, at 38 ° C for 10 hours. Subsequently, the temperature was raised to 95 ° C while maintaining the boil for 10 minutes. Once the temperature of the mixture resulting from the previous step 30 dropped to 65 ° C, two decants and sieves were performed to obtain the ointment without plant residues.

Applications of the resulting product were made in areas affected by hemorrhoids, every 12 hours. A decrease in pain was detected and a decrease in 35 was observed

venous dilation between 12 and 36 hours, with reabsorption of the dilated vessels between 3 and 5 days after the first application.

The beneficial effects observed in the patient who is treated with this ointment with a clinical picture of hemorrhoidal crisis stand out above all currently marketed products, 5 with an improvement that allows practically normal activity.

Example 3. Use of a smoothie obtained from a Carpobrotus plant to manufacture a serum and its use by means of a nebulizer for the treatment of nasal congestion.

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To prepare a serum with nasal vasoconstrictor and decongestant activity from Carpobrotus extract, 80% of a Carpobrotus smoothie and 20% of physiological serum were used. Once the final product was obtained, and using a nasal nebulizer, said product was applied in 5 volunteers who suffered nasal congestion every 6 hours, achieving a decongestant effect, from the first application after the first 3 to 4 minutes. 15 In addition, it was found that the suppression of treatment did not produce a new appearance of congestion.

Example 4. Use of stems and leaves of the genus Carpobrotus to manufacture a body oil for the treatment of teleangiectasis or spider veins. twenty

For the preparation of a body oil with vasoconstrictor activity from Carpobrotus extract, the product was taken fresh and kept dried for 48 hours at 45 ° C. Then, it was crushed and mixed with coconut oil 70/30 ratio, at 38 ° C for 10 hours. Subsequently, the temperature was raised to 100 ° C keeping the boiling for 10 minutes. Once the temperature of the mixture resulting from the previous step dropped to 65 ° C, two decants and sieves were performed, to obtain the final body oil without plant residues.

With the application of the resulting product with intervals of 12 hours in areas affected by 30 teleangiectasis or spider veins, a reduction in the affected capillaries of 60% was observed maintaining a 2-week treatment, and an 80% discoloration in 30 days of application.

Example 5. Use of stems and leaves of the genus Carpobrotus to manufacture a body oil for the treatment of burns.

For the preparation of a body oil with vasoconstrictor activity from Carpobrotus extract, the product was taken fresh and kept dried for 48 hours at 45 ° C. 5 After crushing, a 50% weight mixture of carpobrotus, 25% olive oil and 25% carite butter was prepared at 38 ° C for 10 hours. Subsequently, the temperature was raised to 100 ° C while maintaining the boiling for 10 minutes. Once the temperature of the mixture resulting from the previous step dropped to 65 ° C, two decants and sieves were performed, to obtain the body oil without plant residues 10.

The resulting product was applied to sunburn by reducing the redness of the skin and reducing pain on contact with the affected areas.

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The application of the composition in first and second degree burns has also been carried out, achieving a vasoconstriction of the capillaries. In particular, it was possible to decongest the affected area and eliminate pain in a period of less than 30 minutes. The burn was covered with breathable dressings for 5 days by applying the oil every 12 hours, and stable healing was observed with disappearance of pain. twenty

Example 6. Use of at least one plant of the genus Carpobrotus to manufacture ointment with vasocontrictor activity for the treatment of first and second degree burns.

To prepare an ointment with vasoconstrictor activity from the extract of Carpobrotus, the product was taken fresh and it was crushed in cold, with a temperature below 50 ° C. After crushing, a mixture by weight of 20% proportion of carpobrotus extract and 80% of petroleum jelly was prepared. After a maceration of 60 minutes at 50 ° C, the temperature was raised to 100 ° C while maintaining the boiling for 10 minutes. Once the temperature of the mixture resulting from the previous step dropped 30 to 65 ° C, two decants and sieves were performed, to obtain the ointment without plant residues.

The resulting product was applied on first and second degree burns, achieving a vasoconstriction of the capillaries. In particular, it was possible to decongest the affected area and eliminate pain in a period of less than 30 minutes. He covered the

Burn with breathable dressings for 5 days by applying the oil every 12 hours, and stable healing was observed with disappearance of pain.

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