WO2017130130A1

WO2017130130A1 - Nutritional supplement for maintaining the state of health of the eye

Info

Publication number: WO2017130130A1
Application number: PCT/IB2017/050413
Authority: WO
Inventors: Roberto Pinelli
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-01-28
Filing date: 2017-01-26
Publication date: 2017-08-03
Anticipated expiration: 2018-07-28
Also published as: CH712067A2

Abstract

A composition comprising (a) dry extract of Centella asiatica and (b) at least one nutrient selected from (b1) lutein, (b2) resveratrol, and (b3) dry extract of Vaccinium myrtillus; its use in maintaining the state of health of the eye is a further object of the invention.

Description

NUTRITIONAL SUPPLEMENT FOR MAINTAINING THE STATE OF HEALTH OF THE EYE FIELD OF THE INVENTION

The present invention relates to the technical field of nutritional supplements, also known as dietary supplements; their use in maintaining the state of health of the eye is a further subject matter of the invention.

BACKGROUND ART

Sight is one of the most important senses of the human body and depends to a large extent on the good operation of the central part of the retina, known as macula, and on the macular pigments that are present therein, lutein and its isomer zeaxanthin.

It is known that lutein, which is present in the Calendula flower and belongs to the class of carotenoids, has a role in protecting the eye from oxidative stress by neutralizing the effect of free radicals and in protecting the eye from the high-energy photons of blue light. Several studies have demonstrated that an increase in the pigmentation of the macula decreases the risk of ocular diseases, such as for example age-related macular degeneration (AMD), a disease that damages the macular region on the back of the retina and is currently the main cause of blindness in the world. Loss of vision in AMD can be attributed to the death of the photoreceptors in the central retina. Increasing evidence supports the fact that the causes of the death of photoreceptors and the consequent loss of vision are due to the. damage and death of the cells of the retinal pigment epithelium (RPE), which is caused by several mechanisms, including inflammation and oxidative stress. There are studies which demonstrate that a lutein supplement, alone or in association with other nutrients, protects against AMD. There is also epidemiological evidence that demonstrates that a supplemental amount of lutein and zeaxanthin by means of food or supplements is correlated with a reduced incidence of the opacity of the lens and therefore reduces the risk of the development of cataract. Finally, a study has demonstrated that visual capacity and decrease in sensitivity to light are improved in subjects that assume lutein and zeaxanthin.

Resveratrol, which belongs to the class of stilbenes, is a natural phenol which is found in the peel of several plants, such as for example grapes, bilberries, raspberries, blackberries, etc., and in wine. It has been demonstrated that resveratrol has antioxidant, antiapoptotic, antitumorigenic, anti-inflammatory, anti-angiogenic and vasorelaxant properties. It is known that altered blood flow and consequent ischemias are involved in the pathology of ocular of several ocular diseases, such as age- related macular degeneration (AMD), diabetic retinopathy (DRP) and glaucoma, diseases which cause loss of sight. Oxidative stress is involved in the progression of diseases such as for example primary open-angle glaucoma, one of the main causes of blindness in the world; the forming of cataracts due to age also is associated with an extended oxidative stress, which causes oxidation of the proteins of the lens, thus having a role in the pathogenesis of this disease. Therefore, the administration of resveratrol is capable of preventing the onset and progression of these diseases.

Vaccinium myrtillus or common bilberry is a shrub that grows preferentially in elevated wooded areas of subarctic temperate regions; the main constituents of the drug are anthocyanins, other constituents are tannins, organic acids, flavonol glycosides, terpenes and pectins. Extracts of bilberry fruits as well as anthocyanins have demonstrated that they have an antioxidant and platelet anti-aggregant activity, and a modulating effect on the permeability and resistance of capillaries both in vitro and in vivo. Furthermore, extracts of the bilberry fruit have demonstrated that they improve darkness adaptation of sight in rabbits and have an antiinflammatory activity in the carrageenan induced edema test. The effectiveness of bilberry fruit extracts in the treatment of peripheral vascular diseases has been demonstrated in several clinical studies, in which a reduction of paresthesia, of pain, sense of heaviness in the lower limbs and reduction of the edematous state have been observed. Extracts of bilberry fruit have been found to be effective also in the treatment of sight defects such as for example tapetoretinal degeneration, diabetic retinopathy, in which regression of retinal hemorrhage has been observed, and hypertensive retinopathy.

Centella asiatica, commonly known as centella or gotu kola, is an indigenous herbaceous plant in the Indian subcontinent, in Southeast Asia and in the American Southeast, the leaves and roots of which have a high content of pentacyclic triterpenoids in addition to essential oils, flavonoids, phytosterols, tannins, mineral salts and sugars. It is used in Ayurvedic medicine and in African and Chinese traditional medicines in the treatment of varicose veins, of chronic venous insufficiency, of psoriasis and of wounds. Taking Centella allows to preserve the structure and tone of the vessel walls by virtue of its phlebotonic activity. Centella, by reinforcing and increasing the elasticity of the walls of blood vessels, in fact facilitates correct peripheral circulation and is therefore indicated to prevent and treat varicose veins, reducing vein dilation, capillary permeability and subcutaneous edema. Accordingly, it is useful to treat venous insufficiency and therefore swelling, heaviness of the legs and ankles, and also to contrast vein pain, nocturnal cramps in the lower limbs, hemorrhoids and microangiopathy caused by diabetes. Moreover, the active ingredients of centella have the ability to stimulate fibroblasts in their collagen synthesizing activity, which is indispensable for the health of various tissues, such as the dermis, the connective tissue and the walls of blood vessels. Due to this eudermal and re-epithelizing property, centella is furthermore capable of accelerating the healing of sores, skin lesions, and first- and second-degree burns, ulcer, psoriasis, dermatosis, eczemas. Finally, some studies have demonstrated its effectiveness in the treatment of anxiety and of scleroderma.

Although many nutritional supplements are currently commercially available for maintaining the state of health of the eye, including among others those marketing under the name Lutein omega3®, Macular® active, Macular®Bforte,

3 PROTEZIONE R3TINA® and Eye Health Formula LUTEIN, COMMON BILBERRY &

RESVERATROL, the need is felt to find new nutritional supplements that are effective in maintaining the state of health of the eye.

SUMMARY OF THE INVENTION

The Applicant has studied the compositions of known nutritional supplements for maintaining the state of health of the eye in order to optimize these compositions both from the qualitative standpoint and from the quantitive standpoint and find new compositions that are effective and not toxic.

The Applicant has found surprisingly that a composition comprising Centella asiatica in combination with at least one other nutrient is capable of performing a draining, antioxidant and anti-inflammatory effect, and therefore facilitates the draining of the liquids that can accumulate between the layers of the neuroretina and is very useful in preventing central serous retinopathy, a disease in which edema occurs between retinal layers.

Centella asiatica has a synergistic effect with respect to the antioxidant and photoprotective effect of lutein; with respect to the antioxidant, anti-apoptotic, anti-inflammatory and anti-angiogenic effect of resveratrol; and with respect to the antioxidant, capillary permeability- and strength-modulating, photoprotective and anti-inflammatory effect of Vaccinium myrtillus.

Therefore, the composition according to the present invention comprising Centella asiatica in combination with at least one other nutrient selected from lutein, resveratrol and Vaccinium myrtillus is effective in maintaining the state of health of the eye, in preventing and slowing ocular diseases, improving vision parameters, protecting against degenerative phenomena that occur with age, and protecting the retina from external harmful factors and/or from an excessive exposure to UV rays.

Previously available nutritional supplements comprise compositions that are different from the one of the present invention; furthermore, the present composition provides surprising results if compared with the compositions of known supplements.

Therefore, a first object of the present invention is a composition comprising

(a) dry extract of Centella asiatica

and

(b) at least one nutrient selected from (bl) lutein, (b2) resveratrol and (b3) dry extract of Vaccinium myrtillus.

A second object of the present invention is a capsule that comprises

(a) dry extract of Centella asiatica

and

(b) at least one nutrient selected from (bl) lutein, (bl) resveratrol and (b3) dry extract of Vaccinium myrtillus.

A third object of the present invention is a composition or a capsule as defined above, for use in maintaining the state of health of the eye, and/or in the prevention and/or treatment of ocular diseases associated with age- related macular degeneration (AMD), diabetic retinopathy (DRP), tapetoretinal degeneration, hypertensive retinopathy, central serous retinopathy, glaucoma, cataract.

A fourth object of the present invention is the use of a composition or a capsule as defined above in preparing a medicament for maintaining the state of health of the eye, and/or in the prevention and/or treatment of eye diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), tapetoretinal degeneration, hypertensive retinopathy, central serous retinopathy, glaucoma, cataract.

A fifth object of the present invention is a method for maintaining the state of health of the eye, and/or preventing and/or treating ocular diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), tapetoretinal degeneration, hypertensive retinopathy, central serous retinopathy, glaucoma, cataract in a subject, which comprises the step of administering to such subject an effective quantity of a composition as defined above.

DEFINITIONS

As used herein, the term "prevent" or "prevention" referred to an ocular disease means reducing the incidence of said disorder.

As used herein, the term "treat" or "treatment" referred to an ocular disease means slowing, stopping or reversing the progress. In the preferred embodiment, the treatment of a subject affected by this disease means reversing the progression, ideally to the point of eliminating said disease.

As used herein, the term "administer" or "administration" referred to the composition or to the capsule means that said composition or capsule has been introduced orally in the subject to be treated.

As used herein, the expression "effective quantity" is the quantity of one or more active ingredients that are present in the composition or in the capsule of the present invention which, when administered to a subject, is effective in maintaining the state of health of the eye and/or reducing the incidence of the disorder and/or slowing, stopping or reversing the progression of the disease.

DETAILED DESCRIPTION OF THE INVENTION

The first object of the present invention is a composition comprising (a) dry extract of Centella asiatica

and

In an embodiment according to the first object of the invention, the composition comprises (a) dry extract of Centella asiatica, preferably between 5 and 15 mg, and

(bl) lutein, preferably between 5 and 15 mg or (b2) resveratrol, preferably between 20 and 30 mg, or (b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg.

In another embodiment according to the first object of the invention, the composition comprises

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(bl) lutein, preferably between 5 and 15 mg, and

(b2) resveratrol, preferably between 20 and 30 mg, or (b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg.

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(b2) resveratrol, preferably between 20 and 30 mg, and

(bl) lutein, preferably between 5 and 15 mg, or (b3) dry extract of

Vaccinium myrtillus, preferably between 20 and 30 mg.

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg, and

(bl) lutein, preferably between 5 and 15 mg, or (b2) resveratrol, preferably between 20 and 30 mg.

In a preferred embodiment according to the first object of the invention, the composition comprises

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(bl) lutein, preferably between 5 and 15 mg,

(b2) resveratrol, preferably between 20 and 30 mg, and (b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg.

Preferably, according to the first object of the invention, (a) and/or (bl) is present independently of each other in a quantity of less than 13 mg, more preferably less than 11 mg; greater than 7 mg, more preferably greater than 9 mg; preferably comprised between 7 and 13 mg.

Preferably, according to the first object of the invention, (b2) and/or (b3) is present independently of each other in a quantity of less than 28 mg, more preferably less than 26 mg; greater than 22 mg, more preferably greater than 24 mg; preferably comprised between 22 and 28 mg.

It is possible to use in the present invention commercially available dry extracts respectively of Centella asiatica and Vaccinium myrtillus; preferably, the dry extract of Centella asiatica used in the present invention contains at least 5% of total triterpene derivatives (Italian Pharmacopeia X); preferably, the dry extract of Vaccinium myrtillus used in the present invention contains at least 23.2% and at most 26.4% total anthocyanosides expressed as anthocyanidins (Italian Pharmacopeia X).

The composition according to the present invention can be prepared according to conventional methods that are known to the person skilled in the arts, for example by mixing mechanically the powders of the active ingredients and optionally of the pharmaceutically acceptable excipients by using a mixer, and the resulting mix can be agitated until uniformity is achieved. The resulting mixture can be compacted in order to obtain a tablet, optionally a coating can be applied to the tablet. As an alternative, the resulting mixture can be introduced in a capsule of soft or hard gelatin or into another form of dosage that is known to the person skilled in the art.

According to the invention, the composition as described above can comprise at least one pharmaceutically acceptable vehicle.

The composition according to the present invention can be prepared by using at least one acceptable carrier, mixing it with an effective quantity of active ingredients. Acceptable carriers for oral compositions are the ones commonly used and known to the person skilled in the art.

According to the invention, the composition as described above is suitable for oral administration in the form of a tablet, capsule of soft gelatin, capsule of hard gelatin or other form of dosage that is known to the person skilled in the art. Preferably, the composition of the present invention is in the form of a capsule, more preferably it is in the form of a capsule of soft gelatin.

These capsules have the advantage of passing the gastric barrier.

Moreover, these capsules have the additional advantage that they can be opened so as to make the composition of active ingredients contained therein exit; by administering to a subject the composition dissolved in a beverage, for example in green tea, a faster entry into circulation of the active ingredients contained therein occurs.

A second object of the invention is a capsule comprising

(a) dry extract of Centella asiatica

and

(b) at least one nutrient selected from (bl) lutein, (b2) resveratrol, and (b3) dry extract of Vaccinium myrtillus.

In an embodiment according to the second object of the invention, the capsule comprises

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg, and

(bl) lutein, preferably between 5 and 15 mg, or (b2) resveratrol, preferably between 20 and 30 mg, or (b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg.

In another embodiment according to the second object of the invention, the capsule comprises

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg, (bl) lutein, preferably between 5 and 15 mg, and

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(b2) resveratrol, preferably between 20 and 30 mg, and

(bl) lutein, preferably between 5 and 15 mg, or (b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg.

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg, and

In a preferred embodiment according to the second object of the invention, the capsule comprises

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(bl) lutein, preferably between 5 and 15 mg,

(b2) resveratrol, preferably between 20 and 30 mg, and

(b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg.

Preferably, according to the second object of the invention, (a) and/or

(bl) is present independently of each other in a quantity of less than 13 mg, more preferably less than 11 mg; greater than 7 mg, more preferably greater than 9 mg; preferably comprised between 7 and 13 mg.

Preferably, according to the second object of the invention, (b2) and/or (b3) is present independently of each other in a quantity of less than

28 mg, more preferably less than 26 mg; greater than 22 mg, more preferably greater than 24 mg; preferably comprised between 22 and 28 mg.

A fourth object of the present invention is the use of a composition or a capsule as defined above in the preparation of a medicament for maintaining the state of health of the eye, and/or in the prevention and/or treatment of ocular diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), tapetoretinal degeneration, hypertensive retinopathy, central serous retinopathy, glaucoma, cataract.

According to a preferred embodiment in accordance with the third or fourth object, the use refers to maintaining the state of health of the eye.

According to another preferred embodiment in accordance with the third or fourth object, the use refers to the prevention and/or treatment of ocular diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), central serous retinopathy, glaucoma, cataract; even more preferably, it refers to ocular diseases associated with age-related macular degeneration (AMD).

A fifth object of the present invention is a method for maintaining the state of health of the eye and/or preventing and/or treating ocular diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), tapetoretinal degeneration, hypertensive retinopathy, central serous retinopathy, glaucoma, cataract in a subject, comprising the step of administering to such subject an effective quantity of a composition as defined above.

In accordance with this preferred embodiment, the method relates to the administration of the composition according to the invention in the form of a capsule as defined above.

In a preferred embodiment in accordance with the fifth object of the invention, the method relates to maintaining the state of health of the eye.

In accordance with this preferred embodiment, the method comprises the step of administering the composition, preferably in the form of a capsule, once or twice per day, preferably twice per day, for a period of at least six months; preferably, the method comprises the step of administering the composition, preferably in the form of a capsule, once or twice per day, preferably twice per day, for 3 consecutive months, interrupting the therapy for one month, continuing the therapy for another 3 months.

In a preferred embodiment in accordance with the fifth object of the invention, the method relates to the prevention and/or treatment of ocular diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), central serous retinopathy, glaucoma, cataract; even more preferably, it relates to ocular diseases associated with age-related macular degeneration (AMD).

According to this preferred embodiment, the method comprises the step of administering the composition, preferably in the form of a capsule, twice per day, for a period of at least six months, to be repeated in at least two cycles; preferably, the method comprises the step of administering the composition, preferably in the form of a capsule, once or twice per day, preferably twice per day, for 3 consecutive months, interrupting the therapy for one month, continuing the therapy for another 3 months, interrupting the therapy for one month, continuing the therapy for another 3 months, interrupting the therapy for one month, continuing the therapy for another 3 months.

EXPERIMENTAL PART EXAMPLE 1

A composition that is representative of the invention was prepared, comprising

(a) dry extract of Centella asiatica, 10 mg,

(bl) lutein, 10 mg,

(b2) resveratrol, 25 mg,

(b3) dry extract of Vaccinium myrtillus, 25 mg.

The active ingredients were mixed by using a mixer and the resulting mixture was agitated until uniformity was achieved.

EXAMPLE 2

A capsule that is representative of the invention was prepared, comprising

(a) dry extract of Centella asiatica, 10 mg,

(bl) lutein, 10 mg,

(b2) resveratrol, 25 mg, and

(b3) dry extract of Vaccinium myrtillus, 25 mg.

Capsules adapted for the purpose are known to the person skilled in the art; capsules of soft gelatin were used in the present example.

Claims

1. A composition comprising

(a) dry extract of Centella asiatica

and

2. The composition according to claim 1, comprising

(a) dry extract of Centella asiatica, 5 to 15 mg

and

(bl) lutein, 5 to 15 mg, or (b2) resveratrol, 20 to 30 mg, or (b3) dry extract of Vaccinium myrtillus, 20 to 30 mg.

3. The composition according to claim 1 or 2, comprising

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(bl) lutein, preferably between 5 and 15 mg, and

(b2) resveratrol, preferably between 20 and 30 mg, or (b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg,

or

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(b2) resveratrol, preferably between 20 and 30 mg, and

(bl) lutein, preferably between 5 and 15 mg, or (b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg,

or

(a) dry extract of Centella asiatica, preferably between 5 and 15 mg,

(b3) dry extract of Vaccinium myrtillus, preferably between 20 and 30 mg, and

4. The composition according to any one of the preceding claims, comprising (a) dry extract of Centella asiatica, and/or (bl) lutein in a quantity, independently of each other, of less than 13 mg, more preferably less than 1 1 mg; greater than 7 mg, more preferably greater than 9 mg; preferably comprised between 7 and 13 mg

and/or

(b2) resveratrol and/or dry extract of Vaccinium myrtillus, in a quantity independently of each other of less than 28 mg, more preferably less than 26 mg; greater than 22 mg, more preferably greater than 24 mg; preferably comprised between 22 and 28 mg.

5. The composition according to any one of the preceding claims, comprising

(a) dry extract of Centella asiatica, between 5 and 15 mg,

(bl) lutein, between 5 and 15 mg,

(b2) resveratrol, between 20 and 30 mg, and

(b3) dry extract of Vaccinium myrtillus, between 20 and 30 mg.

6. The composition according to any one of the preceding claims, in the form of a tablet, capsule of soft gelatin or capsule of hard gelatin.

7. A capsule comprising the composition as defined in any one of claims 1 to 5.

8. The composition is defined in any one of claims 1 to 5 or the capsule as defined in claim 7, for use in maintaining the state of health of the eye, and/or in the prevention and/or treatment of ocular diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), tapetoretinal degeneration, hypertensive retinopathy, central serous retinopathy, glaucoma, cataract.

9. The composition or capsule according to claim 8, for use in maintaining the state of health of the eye.

10. The composition or capsule according to claim 8, for use in the prevention and/or treatment of ocular diseases associated with age-related macular degeneration (AMD), diabetic retinopathy (DRP), central serous retinopathy, glaucoma, cataract.