RECTAL PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF PROSTATIC HYPERTROPHY

Abstract: Pharmaceutical compositions suitable for the rectal administration, such as soft-gelatin capsules and suppositories, containing Serenoa repens extract as the active ingredient.

Description: RECTAL PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF PROSTATIC HYPERTROPHY The present invention relates to rectal pharmaceutical compositions for the treatment of prostatic hypertrophy. Particularly, the invention relates to rectal pharmaceutical compositions containing as the active ingredient Serenoa repens extract. Serenoa repens, which is also known as Sabal serrulatum, is a small palm growing in United States, North Africa and Spain, the lipid-sterol extract of which, obtained according to FR-2480754 or EP-68055 patents, has been used for a long time for the treatment of benign prostatic hypertrophy (prostatic adenoma), prostatitis or other prostatic disorders. The therapeutic scheme used up to now envisages the oral administration of 300 - 1000 mg of extract daily. Therapy must generally be continued for at least two months before an improvement in symptomatology can be attained, and sometimes treatment has to be extended even for 3-4 or more months, in order to obtain a complete remission. Now it has been found that Serenoa repens lipid-sterol extracts, administered by the rectal route in form of suitable pharmaceutical compositions, gives beneficial results in patients suffering from prostatic hypertrophy, prostatitis or related pathologies, in surprisingly shorter times compared with the conventional oral therapy. According to the invention, a marked improvement in symptomatology can be evidenced already after one week of treatment, whereas the oral treatment requires about two months of treatment to obtain the same results, as proved in clinical trials in which the two different administration routes were compared according to a double blind evaluation scheme. Therefore, the invention provides pharmaceutical compositions suitable for the rectal administration, containing Serenoa repens extracts as the active ingredient admixed with rectally acceptable carriers. Moreover, the invention relates to the use of the Serenoa repens extract for the preparation of a medicament which can be administered rectally, for the treatment of prostatic disorders, particularly benign prostatic hypertrophy, prostatitis or related pathologies. The present invention also provides a method of treating prostatic disorders, particularly those mentioned above, which comprises administering rectally, a therpeutically effective amount of a Serenoa repens extract to a sufferer in need thereof. The present invention also provides a pharmaceutical composition for use in treatment of prostatic disorders, particularly those mentioned above, which comprises a Serenoa repens extract admixed with rectally acceptable carriers. The Serenoa repens lipid-sterol extract can be formulated, according to the invention, in any form suitable for the enteral or rectal administration, for example suppositories, microclysms, soft-gelatin rectal capsules, rectal ointments, sprays and the like. For this purpose, conventional excipients or carriers and techniques can be used, such as those described in "Remington's Pharmaceutical Science Handbook, Mack Pub. Co., XVII ed, N.Y., USA." As an example, for the formulation of soft- gelatin capsules, an oily dispersion of the active ingredient will be used,obtained using diluents such as plyethylene glycols, vaseline oil, all the vegetable and semi- synthetic officinal oils listed in F.U., Ph. Eur., B.P., USP, Ph. Fr., preferably the medium-chain saturated triglycerids, and dϊspersants such as polyalcόhol fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol esters, • polyoxyethylene sorbitane ester derivatives, saccharose fatty acid esters. Saturated polyglycolysated glycerids are preferably used as dispersants. The formulation can also contain antioxidants, preferably 0.01% butylhydroxyanisole. After that, the oily dispersion is distributed in a lubrified soft-gelatin shell according to known techniques. Alternatively, the same oily dispersion can directly be used to fill microclysms or spray formulations which can be dispensed by suitable dosers. In the case of suppositories, the formulation can contain dispersants such as polyalcohol fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene sorbitane ester derivatives, saccharose fatty acid esters, preferably saturated polyglycolysated glycerids andpolyethylen glycols, polyoxyethylenated hydrogenated oils, all the solid semisynthetic glycerids listed in F.U., Ph. Eur., B.P., U.S.P., Ph. Fr. can be used as diluents for the suppositorium. The formulation can also contain antioxidants, preferably 0.01% butylhydroxyanisole. Li the case of ointments, the formulation can contain, as dispersants, polyalcohol fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene sorbitane ester derivatives, saccharose fatty acid esters, preferably saturated polyglycolysated glycerids. Polyethylene glycols, vaseline oil, all the vegetable and semi-synthetic officinal oils listed in F.U., Ph. Eur., B.P., U.S.P., Ph. Fr., can be used as diluents, medium-chain saturated triglycerids being preferred. Fatty alcohols; vegetable, animal and semi-synthetic waxes, micro-crystalline waxes, solid semi-synthetic glycerids, hydrogenated vegetable oils, preferably U.S. P. hydrognated vegetable oil, can be used as thickening agents. The formulation can also contain antioxidants, preferably 0.01% butylhydroxyanisole. Soft-gelatin capsules containing an oily dispersion of the active ingredient are particularly preferred. The amount of the active ingredient per unit dose will generally range from 50 to 1000 mg, more preferably from 160 to 800 mg. The compositions of the invention will be administered one or more times daily, depending on the severity of the disorder to treat and on the conditions (weight and age) of the patient. Generally, the daily dosage will range from about 160 mg to 3 g, but higher or lower dosages can also be envisaged. Within the dosage ranges indicated above no adverse toxicity effects have been noted. The following example illustrates the invention. Example 1 Oily dispersion distributed in soft-gelatin capsules Formulation of the content of the rectal capsule: Serenoa repens lipid-sterol extract 640 mg Medium-chain saturated triglycerids 100 mg Saturated polyglycolysated glycerids 100 mg 840 mg Preparation method The saturated polyglycolysated glycerids are heated to about 45°C and subsequendy diluted, under stirring, with the medium-chain saturated triglycerids. The dispersion is left to cool to about 30°C, then the Serenoa repens lipid- sterol extracts is added, under stirring. The medicated dispersion is filtered through a 52 microns stainless steel filter and deareated under vacuum. Finally, the dispersion is filled in soft-gelatin capsules, at a dosage of 840 mg/capsule. The content is distributed in a lubrified soft-gelatin shell (rectal capsule) prepared according to the conventional technique. Example 2 Oily dispersion distributed in microclysm Formulation of the rectiola content: Serenoa repens lipid-sterol extract 640 mg Saturated polyglycolysated glyceride 100 mg Medium-chain saturated triglycerids 2,260 mg 3,000 mg Example 3 Suppositorium Formulation of the suppositorium: Serenoa repens lipid-sterol extract 640 mg Saturated plyglycolysated glycerids 100 mg Semisynthetic solid glyceride 2,260 mg 3,000 mg Example 4 Rectal ointment Formulation of the ointment: % Serenoa repens lipid-sterol extract 21,33 Polyglycosylated saturated glyeride 3,33 Hydrogenated vegatable oil U.S.P. 15,00 Medium-chain saturated triglycerids 60,34 The ointment is administered with a rectal cannula at a dosage of 3 g. Example 5 Spray emulsion Formulation of the basic medicated emulsion: % Serenoa repens lipid-sterol extract 23,20 Saturated polyglycolysated glycerids 3,62 100,00 Formulation of the foam: % Basic medicated emulsion 92 Freon 12/114 (50:50) 8 100 The pressurized product is dispensed through a doser valve fitted with a rectal cannula, in an amount of 3 g dose.

Claims: Claims 1. Rectal pharmaceutical compositions containing as the active ingredient a Serenoa repens lipid-sterol extract, in admixture with a rectally acceptable carrier. 2. Compositions according to claim 1, in form of soft-gelatin capsules, suppositories, microclysms, rectal ointments or spray emulsions. 3. Compositions according to claim 2, in form of soft-gelatin capsules. 4. Compositions according to any one of die preceding claims, containing polyglycolysated saturated glycerids as the dispersants. 5. Compositions according to any one of the preceding claims, containing from 50 to 1000 mg of Serenoa repens lipid-sterol extract per unit dose. 6. The use of the Serenoa repens lipid-sterol extract for the preparation of a medicament which can be administered by the rectal route, for the treatment of prostatic disorders. 7. A method of treating prostatic disorders which comprises administering rectally, a therapeutically effective amount of a Serenoa repens extract to a sufferer in need thereof 8. A pharmaceutical composition for use in the treatment of prostatic disorders which comprises a Serenoa repens extract admixed with a rectally acceptable carrier.

Inventors: CROLLA TIZIANA, FRANCESE FRANCO, OLDANI DIEGO, VERCESI GIAN PIERO, CROLLA, TIZIANA, FRANCESE, FRANCO, OLDANI, DIEGO, VERCESI, GIAN, PIERO
Applicants: CROLLA TIZIANA, FRANCESE FRANCO, OLDANI DIEGO, SMITHKLINE BEECHAM FARMA, VERCESI GIAN PIERO, SMITHKLINE BEECHAM FARMACEUTICI S.P.A.
Application year: 1993
Main classification: A61K35
IPC codes: A61K9, A61K36