TR202014196A2 - TOPICAL COMPOSITIONS SUITABLE FOR USE IN SYMPTOMATIC TREATMENT OF ERITROTELENJIECTASIC ROSACEA - Google Patents

Abstract

This invention; containing 0.05-0.1% by weight of xylometazoline in its most basic form; It relates to topical compositions suitable for use in the symptomatic treatment of erythrotelengiectatic rosacea.

Description

DESCRIPTION TOPICAL COMPOSITIONS SUITABLE FOR USE IN THE SYMPTOMATIC TREATMENT OF ERYTHROTHELANGIECTASIC ROSACEA Technical Field This invention; It relates to compositions suitable for topical use in the symptomatic treatment of erythrotelangiectatic rosacea and methods of production thereof. State of the Art Rosacea is a chronic disease characterized by widespread redness on the skin. It develops gradually, starting as redness and irritation of the facial skin. In its later stages, it is characterized by a vascular phase in which patients exhibit increasingly severe erythema (abnormal redness of the skin) and telangiectasia (red streaks caused by abnormal dilation of capillaries and small arteries). In addition, papules, nodules, pimples and blister-like rashes may also develop. These types of rashes often resemble acne, but do not have common acne symptoms such as whiteheads and blackheads. Rhinophyma (nose enlargement) is seen in late stage rosacea. There are multiple types of rosacea described in the literature. Some of those; erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, erythrotelangiectatic rosacea, ocular rosacea are a few of them. Although the pathogenesis of rosacea is unknown, the pathological process of erythema, one of its symptoms, is explained as the expansion of the superficial vasculature of the face. Rosacea patients need topical or oral medications to relieve their distress; However, since the skin of these patients is very easily irritated, the products used have a high probability of causing irritation. Although there is no direct treatment for rosacea, there are treatments to control inflammation and rashes. In such cases, the use of external products can increase the symptoms of rosacea and cause more redness than patients can tolerate. All of these conditions make treating rosacea much more difficult. However, untreated rosacea can lead to irreversible damage to the skin. Antibiotics are the classical first step of therapy. Skin rashes can be controlled with antibiotics such as tetracycline, minocycline, doxycycline or clarithromycin. Alternatively, isotretinoin and antifungal drugs are also symptomatic treatment methods that can be used orally. However, such oral medications often cause side effects that extend beyond the physiological range. Topically applied antibiotics, antifungals and steroids are also among the treatment methods used in the technique. However, the existence of multiple types of rosacea and multiple symptoms specific to these types requires the use of topical medications with separate active ingredients for each symptom. For this reason, the type of this disorder should be well determined and a specific treatment method should be designed. In the patent document numbered TR2017/14097, which is one of the documents in the current technique, a topical formulation containing ivermectin developed for use in the treatment of rosacea is mentioned. It has been described that ivermectin, which carries a macrocyclic lactone ring, has strong antiparasitic activity. In order to improve the hydrolytic stability of ivermectin, it has been formulated so that the active ingredient is in the oil phase. Formulations using alpha-adrenergic agonists are also found in the art. For example; Formulations containing oxymetazoline have been recommended for the treatment of symptoms accompanied by skin redness and capillary dilation, as well as inflammatory wounds, papules and skin thickening. Diagnosis of rosacea varies according to clinical features. Papulopustular rosacea, one of the types of rosacea, manifests itself with blisters, pustules and temporary or permanent capillary erythema. Uneven surface of thickened skin in phymatosis rosaceaida. It presents symptoms in the form of lumps and enlargements in different facial areas. Ocular rosacea, on the other hand, is characterized by red, dry and irritated eyes and eyelids. Erythrotelangiectatic type rocacea may be similar to seborrheic dermatitis. In other words, in addition to capillary dilation and redness, dryness and flaking of the skin are also observed. Considering the applications in the current technique, it is seen that the success rates of antibiotics, emollients and short-term low local corticosteroids are quite low. After topical corticosteroids used to reduce skin redness are discontinued, there is a risk of the skin becoming worse due to the rebound effect. Antibiotics are more effective in types of rosacea that present with pustules, but they have little effect on skin redness. As a result of the research, it has been observed that there are insufficient topical formulations suitable for use in the systemic and symptomatic treatment of erythrotelangiectatic rosacea. In this direction; It is thought that there is still a need for a topical tormulation that provides solutions to many complaints, including redness, capillary dilation, dryness, flaking and itching. Brief Description of the Invention The present invention; It relates to topical compositions suitable for use in the symptomatic treatment of erythrotelangiectatic rosacea, which meet the above-mentioned requirements, eliminate all disadvantages and bring some additional advantages. The primary purpose of the invention is; Our aim is to develop topical compounds that provide solutions to the problems of redness and capillary expansion, which are the most common symptoms of rosacea, while also providing long-term solutions to dryness and related flaking, itching and burning disorders. Another purpose of the invention is; To develop topical compositions containing at least one specifically selected alpha-adrenergic agonist. Another purpose of the invention is; To develop topical compositions containing xylometazoline. Another purpose of the invention is; To develop topical compositions in which the active ingredient is combined with excipients that provide moisturizing. Another purpose of the invention is; To develop topical compositions in the form of cream, gel, pomade, lotion, ointment, emulsion, microemulsion, milk, serum, aerosol, spray, dispersion, foam, solution, vesicle or microcapsule. The invention is a topical composition suitable for use in the symptomatic treatment of erythrothelangiectatic rosacea and contains xylometazoline in its basic form. The preferred application contains 0.05-0.1% xylometazoline by weight. The structural and characteristic features and all the advantages of the invention will be more clearly understood thanks to the detailed explanation given below. Therefore, the evaluation must be made taking into account the detailed explanation. Detailed Description of the Invention In this detailed description, the preferred embodiments of the topical compositions suitable for use in the symptomatic treatment of erythrothelangiectatic rosacea, which is the subject of the invention, are explained for a better understanding of the subject and in a way that does not create any limiting effects. Meet; It is a topical composition suitable for use in the symptomatic treatment of erythrotelangiectatic rosacea*; In its most basic form, it contains 0.05-0.1% xylometazoline by weight. Xylometazoline is an active substance from the alpha-adrenergic agonist class that reduces the symptoms of nasal congestion, allergic rhinitis and sinusitis when used orally. The invention benefits from its decongestant properties when used topically. In addition, the fact that xylometazoline has a much longer half-life compared to other alpha-adrenergic agonists increases the effect of the topical composition of the invention, thus enabling a more effective treatment with less product. Accordingly, the risk of irritation is reduced and patient compliance is increased. The topical composition of the invention is in a form selected from the group including cream, gel, ointment, lotion, ointment, em'ulsion, microemulsion, milk, serum, aerosol, spray, dispersion, foam, solution, vesicle and microcapsule forms. According to one embodiment of the invention; The topical composition of the invention also contains at least one additional auxiliary substance selected from the group consisting of preservatives, gel-forming agents, solvents, thickeners, moisturizers, lubricants, emulsifying agents and flavoring agents. Accordingly, the topical composition, according to a preferred embodiment of the invention, also contains glycerin, cetearyl isocyanate, glyceryl stearate, PEG-100 stearate, myreth-3 myristate, isopropyl myristate, cyclomethicone, dimethicone, steareth-21, steareth-ZO, cetetocopheryl acetate, mannitol. , xylitol, rhamnose, fructooligosaccharides, Iaminaria ochroleuca extract, triethanolamine, cetyl alcohol, stearic acid, acrylates, disodium EDTA, carbomer, caprylic/capric triglyceride, phenoxyethanol, methylparaben, propylparaben, b'utilparaben, ethylparaben, petroleum jelly, behentrimonium methofate, Contains potassium sulfate, ethylhexylglycerin, sodium Iauryl, lactylate, dipotassium phosphate, ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, xanthan gum, sodium hyaluronate, allantoin, safflower oil, castor oil, decyl oleate, octyl dodecanol, octyl palmitate, alkyl benzoate. It contains at least one excipient selected from the group. According to a more preferred embodiment of the invention, the topical composition contains 0.05-0.1% xylometazoline as well as glycerin, glyceryl stearate, petroleum jelly, caprylic/capric triglyceride, myreth-3 myristate, isopropyl myristate, safflower oil, castor oil, decyl oleate, octyl dodecanol, It contains at least one of moisturizing and lubricants containing octyl palmitate, alkyl benzoate. Thanks to the synergistic effect of moisturizer and/or lubricant together with xylometazoline, the topical composition of the invention eliminates the symptoms of redness and vascular dilation caused by rosacea, while simultaneously providing a solution to the complaints of dryness, flaking and itching specifically caused by erythrothelangiectatic rosacea. The use of these auxiliary substances ensures the creation of a layer on the skin, thus preventing moisture loss in the skin and maintaining its water content. It has been observed that if the topical composition of the invention contains the above-mentioned excipients and 0.05-0.1% xylometazoline, a homogeneous mixture is achieved and accordingly its stability and skin penetration are improved. In one embodiment of the invention, the topical composition; xylometazoline or a pharmaceutically acceptable salt thereof, glycerin, cetearyl isocyanate, glyceryl stearate, PEG-100 stearate, mireth-3 myristate, cyclomethicone, steareth-21, tetocopheryl acetate, mannitol, xylitol, rhamnose, fructooligosaccharides, Iaminaria ochroleuca extract, triethanolamine. Contains cetyl alcohol, stearic acid, C10-30 alkyl acrylate crospolymer, disodium EDTA, carbomer, caprylic/capric triglyceride, phenoxyethanol, methylparaben, propylparaben, butylparaben, ethylparaben. The invention is also a method for the production of the topical composition of the invention; I. Mixing excipients containing at least one lubricant and/or moisturizer ii. Adding a solution containing 1mg/ml xylometazoline into the excipients iii. It includes the steps of mixing the mixture until it becomes homogeneous. In the method of the invention, the lubricating and moisturizing agents mentioned in step (i) are glycerin, glyceryl stearate, petroleum jelly, caprylic capric triglyceride, myreth-3 myristate, isopropyl myristate, safflower oil, castor oil, decyl oleate, octyl dodecanol, octyl palmitate. is selected from the group consisting of alkyl benzoate. In the preferred application of the method of the invention, the weight ratio of the xylometazoline solution mentioned in the process step (ii) to the total excipient mixture is between 0.5:1 and 1.5:1, and according to the most preferred application, this ratio is 1:1. The rebound effect of the topical composition produced by the method of the invention is below 1%. In addition, the composition of the invention is suitable for long-term use as it does not pose a risk of irritation on the skin. In an embodiment of the invention; The topical composition produced by the method of the invention is in solution form; It is preferably stored in dropper bottles at room temperature below 25°C or in the refrigerator. The topical composition of the invention; After the skin is thoroughly cleaned and dried, applying it in a thin layer twice a day, in the morning and in the evening, provides the desired symptomatic treatment. TR