|Title of Invention||
"A PHARMACEUTICAL COMPOSITION USEFUL FOR TOPICAL ADMINISTRATION COMPRISING AS ACTIVE INGREDIENTS PROANTHOCYANIDINS"
|Abstract||The present invention relates to a pharmaceutical composition useful for topical administration, comprising as active ingredients proanthocyanidins in the form of complexes with phospholipids in an amount of from 0.01 to 0.1%, glycyrrhetinic acid in an amount of from 0.1 to 5%, telmesteine in an amount of from 0.01 to 1% and at least one compound selected from alpha-bisabolol, zinc pidolate, allantoin, piroctone olamine with a suitable carrier such as herein described and other optional ingredients.|
|Full Text||TOPICAL PHARMACEUTICAL COMPOSITIONS COMPRISING PROANTHOCYANIDINS FOR THE TREATMENT OF DERMATITIS
The present invention relates to pharmaceutical compositions for the topical administration comprising as active ingredients proanthocyanidins, glycyrrhetinic acid and telmesteine, in admixture with a suitable carrier.
The topical pharmaceutical compositions of the present invention are useful for the treatment of inflammatory conditions of the skin, such as atopic dermatitis, allergic contact dermatitis, seborrheic dermatitis, radiation dermatitis, psoriasis, xerosis and atopia as well as of mucosae and eye inflammatory conditions.
Dermatites are superficial skin inflammations, characterized by vesicles, erythema, edema, oozing, scaling or crusting lesions and intense itching. Various types of dermatitis exist: contact dermatitis, which can be caused by irritants with which the skin is in contact or by non-irritating substances to which the subject is allergic; atopic dermatitis, a chronic disease characterized by strong itching; seborrheic dermatitis, a scaling disease which mainly affect the face and scalp. In principle, the treatment consists in removing the offending agent, which however cannot in many cases be identified or removed. Treatment is therefore based on corticosteroids, which have however well known side-effects: they reduce the immune defenses, which can induce infections, mainly by fungi or Candida; suspension of the treatment should be gradual; they cannot be used during the acute oozing phase; a rebound effect may appear on stopping treatment. Furthermore, corticosteroids should not be used for prolonged treatments, particularly in children, since they can give rise to systemic effects.
In the case of seborrheic dermatitis, alternative treatments, based on hydrogenated vegetable oils or hydrophilic petrolatum, or medicated
shampoos (based on zinc-pirithione, selenium sulfide, sulfur and the like) in are not resolutive.
In case of the mucosae inflammatory conditions, in particular of mouth, gingival, rectal, vaginal and eye mucosae, a number of topical treatments are available, including the use of steroidal or non-steroidal antiinflammatory agents, with the problems and side effects characteristics for these medicaments.
Different uses of proanthocyanidins have been described in the pharmaceutical and cosmetic fields. EP 0 694 305 discloses topical compositions of proanthocyanidins combined with coumarins (esculoside and the like) for the treatment of peripheral vasculopathies, such as bedsores, scars, couperose, varices and the like. US 5,470,874 describes a combination of proanthocyanidins and vitamin C for the topical use, as sunscreen, for stimulating collagen synthesis and for restoring damaged collagen. Finally, JP 6,336,421 relates to topical formulations of proanthocyanidins combined with anti-inflammatories, among which glycyrrhetinic acid and derivatives are cited, for the cosmetic use and against sunburns. However, to date the use of proanthocyanidins in the treatment of pathologies such as chronic dermatitis, seborrheic dermatitis and allergic dermatis has not been described.
Proanthocyanidins are widely diffused in a number of vegetable species. They are vegetable extracts containing bioflavonoids, with well-defined chemical profile, consisting for about 15% of dimers, about 20% of trimers and tetramers, and of small amounts of catechin and epicatechin. Proanthocyanidins exert both skin protecting action from the aggression by free radicals and restoration action of the damages to the skin structure through stimulation of collagen production. They also contain essential fatty acids similar to those of the skin hydrolipidic barrier, which contribute to keep said barrier intact. Finally, proanthocyanidins reduce the concentration of enzymes such as elastase, collagenase, hyaluronidase and beta-glucuronidase, which are
responsible for the destruction of elastin, collagen and hyaluronic acid proteins. Therefore, proanthocyanidins are widely used in the pharmaceutical and cosmetic industries, thanks to their restoring, regenerating, nutrient and restructurant actions, which restores the skin elasticity and tonicity.
According to the present invention, the proanthocyanidins extracted from grape seeds and skin of Vitis vinifera are particularly preferred. Most
preferred are the complexes of proanthocyanidins from Vitis vinifera with phospholipids, prepared according to the process disclosed in US 4,963,527.
18-P-Glycyrrhetinic acid, extracted from the roots of Glycyrrhiza glabra, is known to have antiinflammatory properties on the skin, in particular in case of burns and redness.
Telmesteine (N-carbethoxy-4-thiazolidinecarboxylic acid) exerts antiradicalic and protective action against the oxidizing agents responsible for skin damages, as well as inhibiting elastase and collagenase actions.
The topical pharmaceutical compositions of the present invention will contain the active ingredients in admixture with a suitable carrier, preferably a carrier rich in polyunsaturated fatty acids. According to the invention, suitable carriers comprise squalene, fatty acids, fatty acids esters, vegetable oils, natural or synthetic triglycerids. More preferably, suitable carriers comprise squalene, karite butter, octyl palmitate and Oenothera oil.
In particular, karite butter (also known as shea butter) is a fat consisting of a mixture of saturated and unsaturated fats, extracted from the seeds of Butirospennum parkii, a tree from northern Africa, which is used in cosmetics thanks to its protective and softening actions, which make it particularly useful for sensitive skins as well as for skins which easily redden.
Oenothera oil (also known as evening primrose oil), extracted from the plant Oenothera biennis, is rich in essential polyunsaturated fatty acids, in particular y-linolenic acid, indispensable for regenerating the skin and all
According to a preferred embodiment, the pharmaceutical compositions of the invention will further contain compounds with antioxidizing activity, such as tocopherols and ascorbic acid or esters thereof, preferably tocopherol acetate and ascorbyl palmitate or tetrapalmitate, to further increase the protective effect on cell membranes and to slow down the oxidation of polyunsaturated fatty acids.
The compositions of the present invention may further contain other active ingredients, with complementary or anyway useful actions in the treatment of dermatosis.
Examples of said active ingredients are:
salicylic acid, which exerts a keratolytic action useful for the treatment of
hyaluronic acid, which is useful for the treatment of radiation dermatitis
due lo its hydrating and healing action;
alpha-bisabolol, one of the active principles present in chamomile essential
oil (Matricaria flos), which has lenitive and anti-redness action;
zinc pidolate, which exerts slightly astringent, emollient and lenitive
actions, blocks and prevents the formation of free radicals thanks to its
competitive action towards iron ions, and is active in the enzymatic
processes of skin metabolism;
allantoin which has astringent, slightly keratolytic and healing actions;
moisturizers or wetting agents;
piroctone olamine (octopirox), a known agent with antiseborrhoic activity.
Therefore, a further preferred embodiment relates to the pharmaceutical compositions of the invention also containing salicylic acid, for the treatment of seborrheic dermatitis.
A further preferred embodiment relates to the pharmaceutical
compositions of the invention also containing hyaluronic acid, for the treatment of radiation dermatitis.
A further preferred embodiment relates to the pharmaceutical compositions of the invention also containing alpha-bisabolol and allantoin.
A further preferred embodiment relates to the pharmaceutical compositions of the invention also containing zinc pidolate.
The topical pharmaceutical compositions of the present invention can be in the form of cream, gel, lotion, suspension, spray, ointment, foam.
The topical pharmaceutical compositions of the present invention will contain the active ingredients in the following concentrations (w/w):
a) proanthocyanidins in the form of complexes with phospholipids: 0.01% to 1%;
b) glycyrrhetinic acid: 0.1 to 5%, preferably 1 to 2%;
c) telmesteine: 0.01% to 1%; and
- carriers (squalene, karite butter, octyl palmitate and Oenothera oil): 10-50%;
- antioxidants (tocopherol acetate 0.5-5%; ascorbyl palmitate 0.01-0.1%);
- salicylic acid 0.1-5%;
- hyaluronic acid 0.1-10%;
- alfa-bisabolol 0.1-3%;
- zinc pidolate 0.01-1%;
- allantoin 0.1-2%.
The daily dosage will be determined by the physician; by way of example, it will consist of one or more daily applications even for protracted times.
Some examples of formulations according to the present invention are shown hereinafter.
Example 1 CREAM
Example 2 CREAM
Example 3 CREAM
Example 4 CREAM
Example 5 CREAM
Example 6 CREAM
Example 8 CREAM
The compositions of the present invention showed very good tolerability. They do not contain allergenic substances, derivatives from animal sources (such as lanolin, beeswax, animal fat), preservatives (such as parabens, isothiazolones, phenol derivatives, and the like) which are often responsible for allergic contact dermatitis.
Therefore, thanks to the above mentioned characteristics, the compositions of the present invention are useful for the treatment of already existing skin allergic reactions, for the prevention of recurrent forms, and as adjuvants in the treatment of chronic diseases such as atopic dermatitis, allergic contact dermatitis, seborrheic dermatitis, radiation dermatitis, xerosis and atopia.
More particularly, the compositions of the present invention are useful in the treatment of conditions such as irritative and eczematous dermatitis, as moisturizers and lenitive agents for sensitive, delicate skin; in allergic irritations due to medicaments, detergents, solvents; in erythema due to excessive exposure to sun radiaitons; in case of insect stings, redness of various origin, post-shaving irritations, slight burns, skin hyper-reactivity; as normalizers after esthetic treatments, such as peeling with acid glycolic or laser-therapy.
The excellent tolerability of the compositions of the present invention makes them also suitable in pediatrics.
The present invention also relates to the use of proanthocyanidins for the preparation of a topical medicament for the treatment of skin inflammations, in particular atopic, dermatitis, allergic contact dermatitis, seborrheic dermatitis, radiation dermatitis, xerosis, psoriasis and atopia; and of mucosae inflammatory conditions, in particular of vaginal, rectal, eye gingival and buccal mucosae.
1. A pharmaceutical composition useful for topical administration, comprising as active
ingredients proanthocyanidins in the form of complexes with phospholipids in an amount of
from 0.01 to 0.1%, glycyrrhetinic acid in an amount of from 0.1 to 5%, telmesteine in an
amount of from 0.01 to 1% and at least one compound selected from alpha-bisabolol, zinc
pidolate, allantoin, piroctone olamine with a suitable carrier such as herein described and
other optional ingredients.
2. The pharmaceutical composition as claimed in claim 1, in which the carrier comprises
squalene, fatty acids, fatty acid esters, vegetable oils, natural or synthetic triglycerides.
3. The pharmaceutical composition as claimed in claim 2, in which the carrier comprises
squalene, karite butter, octyl palmitate and Oenothera oil.
4. The pharmaceutical composition as claimed in claim 1, comprising tocopherols, ascorbic
acid or esters thereof.
5. The pharmaceutical composition as claimed in claim 1, comprising tocopherol acetate and
ascorbyl palmitate or tetrapalmitate.
6. The pharmaceutical composition as claimed in claim 1, comprising salicylic acid.
7. The pharmaceutical composition as claimed in claim 1, comprising hyaluronic acid.
8. The pharmaceutical composition as claimed in claim 1, in which glycyrrhetinic acid is
present in concentrations ranging from 1 to 2%.
9. The pharmaceutical composition as claimed in claim 1, comprising wetting agents and
10. The pharmaceutical composition as claimed in claim 1, in the form of a cream, gel, lotion, suspension, spray, ointment or foam.
|Indian Patent Application Number||3006/DELNP/2004|
|PG Journal Number||12/2012|
|Date of Filing||01-Oct-2004|
|Name of Patentee||SINCLAIR PHARMACEUTICALS LIMITED|
|Applicant Address||BOROUGH ROAD, GODALMING, SURREY GU7 2AB U.K|
|PCT International Classification Number||A61K 35/78|
|PCT International Application Number||PCT/EP2003/03329|
|PCT International Filing date||2003-03-31|