Απ: Νεα ερευνα-πολυεργαλειο Κορεατων
Kos να το αρχίσουμε η όχι ??
επίσης κάνοντας ένα γύρο στο γοογλη βρήκα αρκετές παρενέργειες... με την απο του στόματος χορήγηση...
Γιατί ρε σεις δεν κάνουμε το εξής κος ας πούμε εσύ που το παίρνεις στην 2η εβδομάδα δεν μπορείς να κάνεις μέτρηση της περιεκτικότητας στο ορό αίματος για να δούμε πόσο περνάει στην συστημική κυκλοφορία ? 7,5% δεν σας φαίνεται μεγάλη συγκέντρωση ?? αλλάζει την χημεία του εγκεφάλου απο το στόμα.... προσοχή όχι να πάμε για μαλλιά και να καταντήσουμε με πάρκινσον.... :-[
επίσης Κος για κοίτα εδώ
http://clinicaltrials.gov/ct2/show/NCT01548066
η έρευνα του πρέπει να έχει ολοκληρωθεί .. δεν του στέλνεις κανα mail ?? ?
εδώ
http://www.freepatentsonline.com/EP1839656.html
κάνει λόγο για ΕΚΠΛΗΚΤΙΚΑ αποτελέσματα κατά της ακμής....
The present invention provides a surprising therapeutic beneficial use for the topical application of valproic acid as a single agent therapy for patients suffering from mild to moderate acne vulgaris. Topically applied VPA has a clinical efficacy comparable to that of the marketed standard medication for this indication, isotretinoin. Furthermore, topically applied VPA is on average well to very well tolerated. The invention relates to the topical medical use of VPA for the treatment of acne vulgaris and comprises the topical application of VPA or of a pharmaceutically acceptable salt thereof.
SUMMARY OF THE INVENTION
The present invention provides a surprising new medical use for patients suffering from acne vulgaris or other types of acne when VPA is applied topically as the single therapeutic agent.
The invention therefore relates to the use of a histone deacetylase inhibitor for the manufacture of a medicament for the topcial treatment of acne.
The medicament can be used for the treatment of non-inflammatory and inflammatory acne lesions.
A preferred histone deacetylase inhibitor is valproic acid (VPA), or pharmaceutically acceptable derivatives or prodrugs thereof. Further histone deacetylase inhibitors include hydroxamic acid derivatives, benzamides, pyroxamides and derivatives thereof, microbial metabolites exhibiting HDAC inhibitory activity, fatty acids and derivatives thereof, cyclic tetrapeptides, peptidic compounds, HDAC class III inhibitors and SIRT inhibitors. Examples are LAQ824, LBH589, Trichostatin A, Suberoyl anilide hydroxamic acid, CBHA, Pyroxamide, Scriptaid, CI-994, CG-1521, Chlamydocin, Biaryl hydroxamate such as A-161906, Bicyclic aryl-N-hydroxycarboxamides, PXD-101, MGCD0103, TPX-HA analogue (CHAP), Oxamflatin, Trapoxin, Depudecin, Apidicin, MS-275, Pivanex (Pivaloyloxymethyl butyrate), trapoxin A, Depsipeptide (FK-228), Tacedinaline, MG2856.
Preferably, the composition which is topically applied to the skin of the patient comprises the histone deacetylase inhibitor (e.g. VPA) at a concentration of from 1% to 4% by weight, and the active ingredient is suspended in a pharmaceutically acceptable carrier.
In a preferred aspect, the histone deacetylase inhibitor is topically applied once to three times daily at an accumulated total daily dose of from 0.5 mg to 200 mg per 1 cm2 of lesion, more preferably of from 2.0 mg to 50 mg per 1 cm2 of lesion. The total amount of topically applied medicament may be 2.000 mg or less per day, and the total amount of the topically applied histone deacetylase inhibitor may be 60 mg or less per day.
The serum concentration of the histone deacetylase inhibitor in a treated patient is usually less than 12.0 µg/ml, preferably less than 4 µg/ml, after repeated topical application over a period of at least 56 days, e.g. over a period of from 56 to 85 days.
Surprisingly, the treatment shows very good tolerability, e.g. it does usually not cause erythema or pain at the site of application. Generally, the local tolerability of the medicament is higher than that of isotretinoin.
The treatment may further comprise administration of a further active agent in a combination therapy. The further active agent may be a histone deacetylase inhibitor other than VPA or it may be a compound that is not an HDAC inhibitor. Examples of further active agents include antibiotics, retinoids, hormonal agents and topical bactericidals such as benzoyl peroxide.
In another embodiment, the histone deacetylase inhibitor (e.g. VPA) is the only active agent in said treatment, i.e. it is used in a monotherapy for treating acne.
The invention further relates to a pharmaceutical composition comprising (i) a first active agent which is a histone deacetylase inhibitor, and (ii) a second active agent which is selected from the group consisting of histone deacetylase inhibitors other than the first active agent, antibiotics, retinoids, hormonal agents and topical bactericidals. The invention further relates to a pharmaceutical kit for the treatment of acne, comprising (i) a first active agent which is a histone deacetylase inhibitor, and (ii) a second active agent which is selected from the group consisting of histone deacetylase inhibitors other than the first active agent, antibiotics, retinoids, hormonal agents and topical bactericidals.
In general, the present invention provides novel possibilities to treat acne vulgaris. Applicants found that the HDAC inhibitory and cellular differentiation-inducing activity of VPA can be used successfully alone, i.e. as a novel monotherapy treatment, for the topical treatment of acne vulgaris, thereby displaying good local tolerability for patients.
