Commiphora mukul extracts and therapeutical applications thereof

Abstract: The present invention relates to new therapeutic uses of lipophilic extracts of Commiphora mukul , prepared from exudate of said plant, as well as the preparation of pure compounds or highly standardized fractions thereof as active ingredients. The extracts, the fractions thereof or the single pure active ingredients isolated therefrom proved to be useful in the treatment of inflammations, both of allergic origin and not, concerning skin and external mucosae, and in the symptomatic treatment of benign prostatic hypertrophy and in the resolutive treatment of acne.

Description: The present invention relates to new therapeutical applications of extracts, fractions and single active ingredients prepared from Commiphora mukul . The Commiphora mukul (Hook, ex Stocks) Engl. (syn. Balsamodendron mukul Hook) is a small tree of the Burseraceae family, endemic in the Indian peninsula, growing spontaneously in the dry and semidry Rajasthan, Gujarat and Madhya Pradesh districts in India, and in Beluchistan district in Pakistan. If the trunk is etched, the plant emits a yellowish gummy exudate, which coagulates rapidly in the form of stalactites having balsamic smell. In the ancient Sanskrit, this gum resin is called guggulu and is a product which is still used in Indian popular medicine for the treatment of obesity and some arthritic forms. Recently, a lipophilic extract has been prepared from this resin, said extract containing many classes of compounds, among which lignans, terpenes and some keto-steroids, named Guggulsterones. Hypolipidemic and platelet aggregation inhibiting activities are described for said lipophilic extract, which is normally obtained by simple resin extraction with ethyl acetate, or for Guggulsterone-Z and Guggulsterone-E, whose components in the extract are normally titrated. By studying said resin, it has surprisingly been found that the lipophilic extract or some fractions therefrom have a marked antiinflammatory and immunomodulating activity, further, the total lipophilic extract, as well as the total steroidal fraction from which it can be derived, have an antiandrogenic activity, useful in acne affections and in benign prostatic hypertrophy. The products of the present invention, when administered by epicutaneous route, proved to have a surprisingly antiinflammatory activity, which is comparable to hydrocortisone and indomethacin ones, when administered by the same route. Guggulsterone-enriched fraction activity in croton oil test, carried out according to the method described in Agents Actions, 17 , 347, 1985, is hereinafter described by way of example. Croton oil oedema inhibition in the mouse from Commiphora mukul total extract and Guggulsterone enriched fraction. Substance Dose/µg Oedema/mg % Reduction p< Controls -- (36) 6,9 ± 0,3 -- -- Tot. extr. 80 (14) 3,8 ± 0,4 44,9 0,001 800 (14) 2,0 ± 0,4 71,9 0,001 Guggulst.-enriched fraction 24 (15) 5,1 ± 0,5 26,1 0,001 80 (27) 3,0 ± 0,3 56,5 0,001 260 (13) 1,5 ± 0,3 78,3 0,001 800 (14) 0,6 ± 0,1 91,3 0,001 Indomethacine 60 (14) 2,9 ± 0,4 58,0 0,001 The Guggulsterones extracted from the total steroidal fraction, deriving from the total lipophilic extract, which has been obtained from the resin of Commiphora mukul bark, have antiandrogenic activity. The Guggulsterone-enriched fraction, used according to the present invention, in clinical tests on dermatological affections, such as atopic dermatitis, psoriasis or inflamed states of various origin, such as U.V. radiation or radiotherapy induced erythema, produces remarkable improvements without causing dryness in the treated part. The fraction containing the Guggulsterones proved to be particularly useful in the treatment of allergic dermatitis; from this result it can be presumed that the Guggulsterones can interfere with the immune system. The enriched fraction, or, in specific cases, pure Guggulsterones (Guggulsterone-Z and Guggulsterone-E) could usefully be employed in the treatment of torpid ulcers and bedsores, as they stimulate cycatrization, probably through macrophage activation. The systemic administration of the Commiphora mukul extracts to patients affected by benign prostatic hypertrophy having a clinical picture characterized by dysuria, diurnal and nocturnal pollakiuria and urinary retention, leads to reduction of the symptomatology, without giving noteworty side effects. The therapeutically useful doses of the Guggulsterone-enriched fraction are comprised between 100 and 1000 mg/day, while the therapeutic doses of the two Guggulsterones ranges from 10 to 150 mg/day. All said products are appropriately incorporated in the most common pharmaceutical compositions. Particularly, for the topical treatment, liposomial lipogels ensure a controlled release and reduce systemic absorption.

Claims: The use of the total lipophilic extract, obtained from the resin of Commiphora mukul bark, for the preparation of an epicutaneous medicament having antiinflammatory activity for the treatment of dermatological affections. The use according to claim 1, wherein said affections are atopic dermatitis, psoriasis, inflamed states of various origin, allergic dermatitis. The use of the total lipophilic extract, obtained from the resin of Commiphora mukul bark, for the preparation of a medicament having antiandrogenic activity. The use of the GUGGULSTERONE-ENRICHED FRACTION, deriving from the total lipophilic extract, which has been obtained from the resin of Commiphora mukul bark, for the preparation of an epicutaneous medicament having antiinflammatory for the treatment of dermatological affections. The use according to claim 4, wherein said affections are atopic dermatitis, psoriasis, inflamed states of various origin, allergic dermatitis. The use of the total steroidal fraction, deriving from the total lipophilic extract, which has been obtained from the resin of Commiphora mukul bark, for the preparation of a medicament having antiandrogenic activity. The use of Guggulsterones extracted from the total steroidal fraction, deriving from the total lipophilic extract, which has been obtained from the resin of Commiphora mukal bark, for the preparation of an epicutaneous medicament having antiinflammatory activity for the treatment of dermatological affections. The use according to claim 7, wherein said affections are atopic dermatitis, psoriasis, inflamed states of various origin, allergic dermatitis. The use of Guggulsterones extracted from the total steroidal fraction, deriving from the total lipophilic extract, which has been obtained from the resin of Commiphora mukul bark, for the preparation of a medicament having antiandrogenic activity.

Inventors: BOMBARDELLI EZIO, SPELTA MICHELE, BOMBARDELLI, EZIO, SPELTA, MICHELE
Applicants: INDENA SPA, INDENA S.P.A.
Application year: 1992
Main classification: A61K35
IPC codes: A61P43, A61P29, A61P17, A61P37, A61K36, A61K31