Patent us20100204320 – pharmaceuticals for xerosis – google patents eczema how to cure

This invention relates to methods and pharmaceutical preparations for preventing or treating pruritic symptoms (the pharmaceutical preparations are hereunder sometimes referred to as antipruritics), in particular, to antipruritic methods and antipruritics effective in eliminating the itch sensation due to atopic symptoms. Get rid of eczema on face More particularly, the invention relates to methods and pharmaceutical preparations for preventing or treating xerosis (the pharmaceutical preparations are hereunder sometimes referred to as pharmaceutical preparations against xerosis), and even more particularly to methods and pharmaceutical preparations effective in eliminating skin damage due to diminished water content of the stratum corneum, decreased lipid between horny cells, etc.

Recent years have seen a rapid increase in the number of patients with pruritic symptoms as from atopic dermatitis and atopic conjunctivitis. Is eczema common in babies Also increasing is the number of patients with chronic dermatoses such as xerosis due to excessive dryness caused by diminished lipid between horny cells of the skin and lowered water content of the stratum corneum, typically associated with aging. Eczema education These diseases are accompanied by an intense itch sensation of obscure etiology and are aggravated by the resulting itch-evoked scratching behavior, possibly inducing inflammations in mucous membranes or skin.


Eczema meaning in marathi Therefore, eliminating an itch sensation, particularly doing so while maintaining the normal water content of the stratum corneum, is crucial to the elimination of those symptoms.

Pharmaceutical preparations conventionally used to treat those cases of chronic dermatitis include steroids for external application, antihistamines, antiallergics and humectants. How is eczema caused However, the use of steroids is restricted for the strong side effects they may cause, and no completely satisfactory therapeutic efficacy has been obtained from antihistamines, antiallergics, humectants, etc. Eczema natural cures diet In addition, diseases that are ameliorated temporarily in symptoms by those drugs will occasionally recur, showing inadequacy in their therapeutic efficacy.

Heretofore, antipruritics have been assessed by administering histamine, serotonin and other pruritogens into the skin of animals and measuring their itch-evoked scratching behavior. Cure for eczema in babies However, it was recently reported that the manifestation of an itch due to pruritic symptoms as in atopic dermatitis is not simply the reaction caused by histamine, etc. Wet eczema baby that are released from mast cells (J. How to cure eczema on fingers Dermatological Science 25, 20-28, 2001). Eczema and dermatitis What is more, on account of unknown etiology for pruritic symptoms from excessive dryness of the skin, no reliable method has been established for assessing the therapeutics available today.

Prostaglandins have been considered to be a prurigenic component (J. Acute eczema on hands Am. Eczema allergy symptoms Acad. Follicular eczema causes Dermatol. Wet eczema pictures 47, 28-32, 2002) but it was recently reported that a prostaglandin receptor agonist is useful as an antipruritic agent against the itch from atopic dermatitis (see WO03/070252). How does eczema start However, many of the substances that act on prostaglandin receptors in general often act not only on a specific receptor but also on other receptors. Is dermatitis and eczema the same thing Therefore, if they act not only on the receptor which should develop the intended pharmaceutical efficacy but also on other receptors, there is the risk of an unwanted physiological reaction of manifesting itself as a side effect or reduced action. Drugs for eczema For example, prostaglandin D2 acts as an agonist not only on the prostaglandin receptors but also on a thromboxane (TP) receptor and it has the possibility of inducing potent vasoconstriction and platelet aggregation which are TP receptor agonistic actions (The Journal of Pharmacology And Experimental Therapeutics (2003), 305, 347-352, Br. Chronic eczematous external otitis J. Nummular eczema Pharmacol. Get rid of eczema rash (1989), 96, 688-692). Dyshidrotic eczema images In the presence of such side effects, the utility of a particular prostaglandin receptor agonist as an antipruritic agent is limited.

An object, therefore, of the present invention is to provide methods and pharmaceutical preparations that depend on a new mechanism of action for preventing or treating pruritic symptoms, in particular, atopic symptoms. Types of eczema cream A specific object of the present invention is to provide highly safe and efficacious methods and pharmaceutical preparations that can prevent or treat the onset of xerosis which is a dermal disease that is accompanied by cutaneous anaphylaxis of obscure etiology, itch sensation or scratching behavior that result from reduced lipid between horny cells of the skin and diminished water content of the stratum corneum.

With a view to attaining these objects, the present inventors made an investigation adopting the method of assessment to be described later and found that certain kinds of prostaglandins had an outstanding antipruritic effect and were particularly effective in controlling the itch sensation accompanying atopic symptoms. Eczema society us In addition, the present inventors studied various drugs that could effectively reduce the transpiration of water content from the skin and found that a prostaglandin D (DP) receptor selective agonist could effectively control excessive dryness of the skin, thus proving effective in preventing or treating conditions such as diminished water content of the stratum corneum. Toddler eczema The present invention has been accomplished on the basis of these findings.

According to yet another embodiment of the present invention, there are provided a method for preventing or treating pruritic symptoms (including atopic symptoms), in particular, xerosis which comprises applying to a mammal a prostaglandin derivative represented by formula [1], provided that 7-[(1R,2R,3R,5R)-5-chloro-2-[(1E,3S)-3-cyclohexyl-3-hydroxy-1-propenyl]-3-hydroxycyclopentyl]-(5Z)-5-heptenoic acid is excluded, a pharmaceutically acceptable salt thereof or a hydrate thereof, as well as a pharmaceutical preparation to be used in the method for prevention or treatment.

The present inventors studied the mechanism of action in itching and excessive dryness of the skin; as a result, they found that NC/Nga mice which would develop dermatitis spontaneously did not experience substantial changes with aging in the contents of prostaglandins PGE 2, PGF 2α, and PGI 2 in the skin tissue but experienced a significant drop in the PGD 2 content with aging. Atopic dermatitis cure These results suggest the possibility that in the NC/Nga mice which will develop dermatitis spontaneously, the decreased in vivo PGD 2 content associated with aging may trigger itching and excessive dryness of the skin. How does eczema affect the skin In other words, the endogenous PGD 2 content has the physiological action of maintaining the skin’s barrier function and the supply of exogenous stable PGD 2 derivatives would contribute to preventing or treating the onset of xerosis.

wherein X is an α- or β-substituted halogen atom, Y is an ethylene group, a vinylene group or an ethynylene group, R 1 is a C 3-10 cycloalkyl group, a C 3-10 cycloalkyl group substituted by C 1-4 linear or branched alkyl group(s), or a C 4-13 cycloalkylalkyl group, R 2 is a group represented by CO 2R 3, wherein R 3 is a hydrogen atom, a C 1-4 linear or branched alkyl group or a C 2-4 linear or branched alkenyl group, n is an integer of 1 to 4, and p is 0, 1 or 2 can be produced by processes according to reaction schemes 1 and 2.

(4) The compound of formula (VII) (or formula (VII′)) is mesylated or tosylated with, for example, 1 to 6 equivalent amounts of methanesulfonyl chloride or p-toluenesulfonyl chloride in a suitable solvent such as pyridine at −20 to 40° C., optionally in the presence of 0.8 to 6 equivalent amounts of 4-dimethylaminopyridine, followed by chlorination with 1 to 16 equivalent amounts of tetra-n-butylammonium chloride to give a compound of formula (VIII) (or formula (VIII′)) (X is a chlorine atom). Baby eczema causes and treatments Bromination and fluorination can also be performed by ordinary methods. Natural eczema remedies for toddlers For example, bromination can be obtained by reacting 1 to 10 equivalent amounts of carbon tetrabromide in acetonitrile in the presence of 1 to 10 equivalent amounts each of triphenylphosphine and pyridine. Eczema skin condition pictures Fluorination may, for example, be obtained by reacting 5 to 20 equivalent amounts of diethylaminosulfur trifluoride (DAST) in methylene chloride.

The dose to be administered of the active ingredient in the antipruritics and pharmaceutical preparations against xerosis according to the invention can be adjusted as appropriate for the body weight of the patient, his or her age, sex, etc. Is eczema contagious diseases Usually, the dosage is 1 ng to 10 mg, preferably 0.1 to 100 μg, per administration and one to several administrations are tolerated per day. Eczema mild face Depending on such factors as age, sex and body weight, the pharmaceutical preparations against xerosis can typically be administered by applying appropriate doses of the preparations to the diseased area at concentrations of the active ingredient ranging from about 0.1 to about 0.0001%.

About 20-week old NC/Nga mice each weighing about 30 g and manifesting atopic dermatitis were purchased from SLC and subjected to the following experiment. Pictures of allergic eczema A magnet was buried in both hind paws of each mouse and by detecting its magnetism, the movement of the paws was measured with an itch measuring system (product of Neuroscience). Eczema around eyes Among the scratching actions, those lasting 1.5 seconds or longer were considered itch-evoked and their number was counted continuously. Eczema in dogs paws Since the itch-evoked scratching behavior had a diurnal rhythm, the diurnal rhythm of each individual animal was measured for 24 hours of the day before test and only after that, compound No. Eczema eyes natural treatment 3 (0.1%), compound No. Asteatotic eczema symptoms 11 (0.1%) or compound No. What causes eczema on scalp 12 (0.1%) dissolved in 100% ethanol was applied to the dorsal skin in a dose of 0.2 ml/mouse. Eczema on the face remedies The subsequent 24-hr itch-evoked scratching behavior was measured and the number of itch-evoked scratchings after drug administration was compared with the initial count. Nummular eczema treatment over the counter The structures of the test compounds are shown below and the changes with time in the spontaneous itch-evoked scratching counts, as well as the 24-hr total spontaneous itch-evoked scratching counts before and after administration of a compound are shown in FIGS. Eczema what is it and causes 2-4.