PL203555B1 - Pharmaceutical compositions containing Tribulus terrestris, Turnera diffusa, Cinnamon cassia extracts and Ginkgo biloba extract and their use for the manufacture of a medicament for the treatment of male and female impotence - Google Patents
Pharmaceutical compositions containing Tribulus terrestris, Turnera diffusa, Cinnamon cassia extracts and Ginkgo biloba extract and their use for the manufacture of a medicament for the treatment of male and female impotenceInfo
- Publication number
- PL203555B1 PL203555B1 PL371674A PL37167403A PL203555B1 PL 203555 B1 PL203555 B1 PL 203555B1 PL 371674 A PL371674 A PL 371674A PL 37167403 A PL37167403 A PL 37167403A PL 203555 B1 PL203555 B1 PL 203555B1
- Authority
- PL
- Poland
- Prior art keywords
- tribulus terrestris
- extracts
- ginkgo biloba
- cinnamon cassia
- arginine
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims description 31
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- 241001521901 Tribulus lanuginosus Species 0.000 title claims description 19
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- 235000009206 Turnera diffusa Nutrition 0.000 title claims description 19
- 235000004952 turnera diffusa Nutrition 0.000 title claims description 19
- 201000001881 impotence Diseases 0.000 title claims description 12
- 239000003814 drug Substances 0.000 title claims description 11
- 238000011282 treatment Methods 0.000 title claims description 11
- 239000009429 Ginkgo biloba extract Substances 0.000 title claims description 10
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
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- 238000002360 preparation method Methods 0.000 claims description 11
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- VNONINPVFQTJOC-UHFFFAOYSA-N polyphyllin III Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C(C1O)OC2C(C(O)C(O)C(C)O2)O)OC(CO)C1OC1OC(C)C(O)C(O)C1O VNONINPVFQTJOC-UHFFFAOYSA-N 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
Description
Opis wynalazku Przedmiotem wynalazku s a kompozycje farmaceutyczne zawieraj ace ekstrakty Tribulus terre- stris, Turnera diffusa, Cinnamon cassia i ekstrakt Ginkgo biloba, przydatne w leczeniu zaburze n czyn- no sci seksualnych u mezczyzn i kobiet oraz ich zastosowanie do wytwarzania leku do leczenia m e- skiej i ze nskiej impotencji. Zaburzenia czynno sci seksualnych maj a istotne znaczenie i stanowia przedmiot intensywnych bada n biomedycznych. Wed lug ostatnich danych statystycznych, problem impotencji pod ró znymi postaciami (brak libido i zaburzenia wzwodu) dotyczy oko lo 70% populacji w wieku oko lo 50 i wi ecej lat. Stopie n impotencji pod ró znymi postaciami ró zni si e oczywi scie stopniem zaawansowania, szcze- gólnie w sród osób starszych, u których jest cz esto fizjologicznie zwi azany z innymi zaburzeniami taki- mi jak choroba serca lub nerek. Obecnie dost epne leki do leczenia takich zaburze n czynno sciowych, szczególnie zaburzenia wzwodu, obejmuj a hormony takie jak testosteron, VIP, pochodne prostaglandyny (PGE 3 )/ oraz srodki sercowo-naczyniowe takie jak papaweryna, fenoksybenzamina i fentolamina. Jednak ze wzgl edu na ich niepo zadane dzia lania uboczne i koniecznosc wstrzykniec do cia l jamistych lub do cewki moczowej np. w przypadku papaweryny i PGE 2 , zaden spo sród tych leków nie zapewnia zadowalaj acego i sta lego rozwi azania tego problemu. Ostatnio, opracowano inhibitory fosfodiesterazy cGMP, które s a szczególnie przydatne w le- czeniu impotencji i wykazuj a dzia lanie po podaniu doustnym. Jeden spo sród tych srodków, nazwany sildenafil (WO 94/28902), znajduje si e ju z na rynku. Jednak, tak ze i tutaj, w zadnym przypadku nie mo zna pomin ac dzia la n niepo zadanych i nadal istnieje du ze zapotrzebowanie na bezpieczniejsze i bardziej skuteczne sposoby leczenia. Obecnie prowadzi si e liczne badania w dziedzinie nowoczesnej farmakologii nad produktami pochodzenia naturalnego (g lównie pochodzenia ro slinnego, ale tak ze zwierz ecego) na podstawie wskaza n pochodz acych z medycyny tradycyjnej, aby oceni c ewentualne podstawy naukowe ich prak- tycznego zastosowania. Badania biochemiczne wykaza ly olbrzymi a z lo zono sc mechanizmów zachodz acych w proce- sach fizjologicznych zwi azanych z aktywno scia seksualn a, takich jak wzwód pr acia i lechtaczki, zwil- zanie scian pochwy, wytrysk nasienia i orgazm. Mediatory takie jak tlenek azotu (NO), enzymy bior ace udzia l w metabolizmie przeka zników cAMP i cGMP, receptory adrenergiczne b lon komórek miesni g ladkich, neuroprzeka zniki dopaminer- giczne, oraz receptory PGE 3 lub innych hormonów stanowi a potencjalne cele w farmakologicznym leczeniu impotencji i innych zaburze n czynno sci seksualnych. Istniej a oczywi scie trudno sci zwi azane z zapewnieniem zadowalaj acego rozwi azania tego kon- kretnego problemu, czesciowo ze wzgl edu na czynniki srodowiskowe i psychologiczne, które poza aspektami natury czysto biochemicznej i fizjologicznej, mog a w wi ekszym stopniu skomplikowa c obraz kliniczny pacjentów cierpi acych na zaburzenia seksualne. Ostatnio stwierdzono, ze zestawienie ekstraktów ro slin leczniczych o swoistych w la sciwo sciach w pewnych stosunkach ilo sciowych daje szczególnie zadowalaj ace wyniki terapeutyczne w leczeniu zaburze n czynno sci seksualnych u mezczyzn i kobiet. Przedmiotem wynalazku s a kompozycje farmaceutyczne, zawieraj ace ekstrakty Tribulus terre- stris, Turnera diffusa i Cinnamon cassia w stosunku wagowym, odpowiednio 1,5-3,5 : 1-2 : 0,1-0,4; ekstrakt Ginkgo biloba i, ewentualnie, arginin e lub jej równowa zny fizjologicznie ester, sól lub prekur- sor, w mieszance z odpowiednim no snikiem lub rozczynnikiem. Korzystnie stosunek wagowy ekstraktów Tribulus terrestris, Turnera diffusa i Cinnamon cassia wynosi 2,5 : 1,5 : 0,2. Korzystnie ekstrakt Ginkgo biloba sk lada si e z frakcji dimerycznych flawonoidów apigeniny, ko- rzystniej gdy dodatkowo zawarto sc frakcji dimerycznych flawonoidów apigeniny wynosi 50 mg. Korzystnie kompozycje wed lug wynalazku zawieraj a ekstrakty Tribulus terrestris, Turnera diffusa i Cinnamon cassia oraz L-arginin e lub chlorowodorek L-argininy w stosunku wagowym, odpowiednio 1,5-3,5 : 1-2 : 0,1-0,4 : 0,5-1,5, korzystniej gdy stosunek wagowy ekstraktów Tribu- lus terrestris, Turnera diffusa i Cinnamon cassia oraz L-argininy lub chlorowodorku L-argininy wynosi 2,5 : 1,5 : 0,2 : 1. Przedmiotem wynalazku jest równie z zastosowanie ekstraktów Tribulus terrestris, Turnera diffusa i Cinnamon cassia w stosunku wagowym, odpowiednio 1,5-3,5 : 1-2 : 0,1-0,4 w po laczeniuPL 203 555 B1 3 z ekstraktem Ginkgo biloba i, ewentualnie, arginin a lub jej fizjologicznie równorz ednymi estrami, solami lub prekursorami, do otrzymywania leków do leczenia zaburze n czynno sci seksualnych u m ezczyzn i kobiet, a szczególnie do leczenia impotencji, zaburzenia wzwodu, zaburzenia libido, ozi eb lo sci i braku orgazmu. Ekstrakty Tribulus terrestris, Turnera diffusa i Cinnamon cassia znane s a i znalaz ly ju z zasto- sowanie dla podobnych celów w niektórych rodzajach medycyny tradycyjnej ale nie s a one znane w zestawieniu, szczególnie w konkretnych stosunkach ilo sciowych wymienionych powy zej. W szczególno sci wiadomo, ze ekstrakt Tribulus terrestris wywo luje syntez e testosteronu, hor- monu odpowiedzialnego za stymulacj e pop edu seksualnego zarówno u m ezczyzn jak i u kobiet; eks- trakt Turnera diffusa, bogaty w olejki eteryczne, przejawia dzia lanie wazodylatacyjne za po srednic- twem uwalniania NO, skutkiem czego ekstrakt przejawia dzia lanie wazomotoryczne na t etnice i t et- niczki; ekstrakt Cinnamon cassia po srednio pobudza libido poprzez dzia lanie na receptory dopaminy zwi azane z odczuwaniem przyjemno sci. W ko ncu, silna przeciw-fosfodiesterazowa aktywno sc dimerycznych flawonów ekstrahowanych z Ginkgo biloba przyczynia si e do rozszerzenia naczy n cia l jamistych, w konsekwencji pot eguj ac na- czyniowe dzia lanie Turnera diffusa. Jednak ze, wyników terapeutycznych otrzymywanych za pomoc a kompozycji wed lug wyna- lazku nie mo zna wyja sni c wy lacznie na podstawie dzia lania poszczególnych ekstraktów; w rze- czywisto sci, nieoczekiwanie okaza lo si e, ze gdy ekstrakty laczy si e w stosunkach ilo sciowych innych ni z te podane powy zej, pozostaj a one nieaktywne, a nawet mog a spowodowa c pogorsze- nie zaburzenia. Rzeczywiste zwi ekszenie aktywno sci seksualnej mo zna wi ec tylko osi agn ac sto- suj ac ekstrakty tych ro slin w dok ladnie okre slonym stosunku, co zwi eksza zarówno libido jak i ukrwienie narz adów p lciowych. Do celów wed lug wynalazku mo zna stosowa c ekstrakty ro slin leczniczych otrzymywane typo- wymi technikami, takimi jak ekstrakcja rozpuszczalnikami lub p lynami w stanie nadkrytycznym. Jednak ze, korzystne jest zastosowanie standaryzowanych ekstraktów o okre slonej zawarto sci pewnych charakterystycznych sk ladników ekstraktu: przyk ladowo, ekstrakt Tribulus terrestris b edzie zawiera l oko lo 40% saponin wyra zonych w po- staci dioscyny; ekstrakt Turnera diffusa jest, korzystnie, ekstraktem lipofilowym; ekstrakt Ginkgo bilo- ba, korzystnie, zawiera dimeryczne flawony w ilo sci oko lo 60%; a ekstrakt Cinnamon cassia, korzyst- nie, zawiera aldehyd cynamonowy w ilo sci oko lo 70%. Do przygotowania ekstraktów stosuje si e ró zne cz esci ro slin, jako ze zawieraj a one aktywne sk ladniki w ró znych st ezeniach. W szczególno sci, ca lej ro sliny u zywa si e do przygotowania eks- traktów Turnera diffusa, korzystnie ekstrahuj ac ditlenkiem w egla w warunkach nadkrytycznych pod ci snieniem pomi edzy 230 i 250 barów, korzystnie 240 barów i w temperaturze pomi edzy 35 i 55°C, korzystnie 40°C; ekstrakty Tribulus terrestris korzystnie otrzymuje si e z nadziemnych cz esci i nasion ro slin poprzez ekstrakcj e 40% mieszanin a etanol/woda, podczas gdy ekstrakty Cinnamon cassia korzystnie wytwarza si e przez ekstrakcj e kory pnia ditlenkiem w egla w warun- kach ci snienia nadkrytycznego pomi edzy 110 i 150 barów, korzystnie 135 barów, w temperaturze 35°C. Ekstrakt Ginkgo biloba korzystnie wytwarza si e z frakcji, w której sk lad wchodz a flawonoidy dimeryczne pochodz ace z apigeniny, wytwarzane np. wed lug EP 360556. Mieszanina ekstraktów wed lug wynalazku powinna by c przyjmowana przez d luzszy czas, a nie tylko bezpo srednio przed stosunkiem plciowym, chocia z u niektórych pacjentów do odpowiedzi na lek dochodzi ju z przy pierwszym za zyciu, w ci agu 30 minut po przyj eciu leku. Podawanie kompozycji wed lug wynalazku nawet przez d lu zszych czas nie powoduje jakichkol- wiek istotnych dzia lan niepozadanych, jest dobrze tolerowane i nie zaburza delikatnej równowagi hormonalnej, szczególnie równowagi androgen/estrogen, która decyduje o wi ekszo sci m eskich i ze n- skich procesów fizjologicznych, takich jak andropauza i menopauza. Przyk lady odpowiednich postaci podawania kompozycji wed lug wynalazku obejmuj a tablet- ki, mi ekkie i twarde kapsu lki zelatynowe, czopki i preparaty do picia zawieraj ace dawki jednost- kowe ekstraktu Tribulus terrestris w zakresie pomi edzy 100 i 300 mg oraz dawki jednostkowe pozosta lych sk ladników zgodne ze stosunkiem wagowym okre slonym powy zej. Szczególnie korzystne s a preparaty sta le, takie jak tabletki o niezmodyfikowanym uwalnia- niu lub tabletki odporne na kwas zo ladkowy lub p lynne postacie do picia. Nast epuj ace przyk lady podano w celu zilustrowania wynalazku.PL 203 555 B1 4 P r z y k l a d 1 - Wytwarzanie tabletek powlekanych Ka zda 700 mg tabletka powlekana zawiera: Tribulus terrestris 250,00 mg Turnera diffusa 150,00 mg Cinnamon cassia 20,00 mg Ginkgo biloba 50,00 mg L-arginina 100,00 mg polisacharydy sojowe 55,00 mg ditlenek krzemu 14,00 mg skrzemionkowana celuloza mikrokrystaliczna 42,00 mg stearynian magnezu 4,00 mg hydroksypropylometyloceluloza 6,40 mg talk 5,20 mg ditlenek tytanu 2,00 mg gliceryna 0,12 mg Polisorbat 80 0,80 mg chinolina 0,43 mg indygotyna 0,05 mg P r z y k l a d 2 - Wytwarzanie twardych kapsu lek zelatynowych Ka zda 340 mg kapsu lka zawiera: Tribulus terrestris 125,00 mg Turnera diffusa 75,00 mg Cinnamon cassia 10,00 mg Ginkgo biloba 25,00 mg L-arginina 50,00 mg polisacharydy sojowe 25,00 mg ditlenek krzemu 7,00 mg silifikowana celuloza mikrokrystaliczna 20,00 mg stearynian magnezu 1,50 mg talk 1,50 mg P r z y k l a d 3 - Wytwarzanie mi ekkich kapsu lek zelatynowych Ka zda 700 mg mi ekka kapsu lka zelatynowa zawiera: Tribulus terrestris 125,00 mg Turnera diffusa 75,00 mg Cinnamon cassia 10,00 mg Ginkgo biloba 25,00 mg L-arginina 50,00 mg lecytyna sojowa 20,00 mg triglicerydy srednio la ncuchowe 100,00 mg Polisorbat 80 10,00 mg olej sojowy 275,00 mg koloidalny ditlenek krzemu 10,00 mg P r z y k l a d 4 - Wytwarzanie roztworu do picia Ka zda 10 ml fiolka zawiera: Tribulus terrestris 250,00 mg Turnera diffusa 150,00 mg Cinnamon cassia 20,00 mg Ginkgo biloba 50,00 mg chlorowodorek L-argininy 100,00 mg gliceryna 3000,00 mg Polisorbat 20 800,00 mg glikol propylenowy 1000,00 mg Acesulfam K 175,00 mg sacharyna sodu 40,00 mgPL 203 555 B1 5 neohesperydyna DC 2,50 mg substancje smakowe 300,00 mg sorbat potasu 11,70 mg metyloparaben 8,30 mg oczyszczona woda q.s. do 10,00 ml P r z y k l a d 5 - Wytwarzanie rozpuszczalnego granulatu Ka zda 5000 mg saszetka zawiera: Tribulus terrestris 250,00 mg Turnera diffusa 150,00 mg Cinnamon cassia 20,00 mg Ginkgo biloba 50,00 mg chlorowodorek L-argininy 100,00 mg Polisorbate 20 500,00 mg Acesulfam K 175,00 mg sacharyna sodu 40,00 mg neohesperydyna DC 2,50 mg substancje smakowe 300,00 mg inulina 1000,00 mg mannitol 2412,50 mg PL PL PL Description of the invention The subject of the invention are pharmaceutical compositions containing extracts of Tribulus terrestris, Turnera diffusa, Cinnamon cassia and Ginkgo biloba extract, useful in the treatment of sexual dysfunctions in men and women, and their use in the preparation of a drug for the treatment of men. female and female impotence. Sexual dysfunction is of significant importance and is the subject of intensive biomedical research. According to recent statistical data, the problem of impotence in various forms (lack of libido and erectile dysfunction) affects approximately 70% of the population aged 50 and over. The degree of impotence in its various forms varies, of course, with the degree of advancement, especially among older people, in whom it is often physiologically associated with other disorders such as heart or kidney disease. Currently available drugs for the treatment of such functional disorders, particularly erectile dysfunction, include hormones such as testosterone, VIP, prostaglandin derivatives (PGE 3 ), and cardiovascular agents such as papaverine, phenoxybenzamine and phentolamine. However, due to their undesirable side effects and the need for intracavernous or urethral injections, e.g. in the case of papaverine and PGE 2, none of these drugs provides a satisfactory and permanent solution to this problem. Recently, cGMP phosphodiesterase inhibitors have been developed which are particularly useful in the treatment of impotence and are effective after oral administration. One of these agents, called sildenafil (WO 94/28902), is already on the market. However, here again, side effects cannot be ignored in any case and there is still a great need for safer and more effective treatments. Currently, numerous studies in the field of modern pharmacology are being conducted on products of natural origin (mainly of plant origin, but also of animal origin) based on indications from traditional medicine, in order to assess the possible scientific basis for their practical use. Biochemical studies have demonstrated the enormous complexity of mechanisms occurring in physiological processes related to sexual activity, such as penile and clitoral erection, wetting of the vaginal walls, semen ejaculation and orgasm. Mediators such as nitric oxide (NO), enzymes involved in the metabolism of cAMP and cGMP transmitters, adrenergic receptors in the smooth muscle cell membrane, dopaminergic neurotransmitters, and PGE 3 or other hormone receptors are potential targets in pharmacological treatment. impotence and other sexual dysfunctions. There are, of course, difficulties in providing a satisfactory solution to this particular problem, partly due to environmental and psychological factors which, beyond the purely biochemical and physiological aspects, can further complicate the clinical picture of patients suffering from suffering from sexual disorders. Recently, it has been found that the combination of extracts of medicinal plants with specific properties in certain quantitative ratios gives particularly satisfactory therapeutic results in the treatment of sexual dysfunctions in men and women. The subject of the invention are pharmaceutical compositions containing extracts of Tribulus terrestris, Turnera diffusa and Cinnamon cassia in a weight ratio of 1.5-3.5: 1-2: 0.1-0.4, respectively; Ginkgo biloba extract and, optionally, arginine or its physiologically equivalent ester, salt or precursor, in admixture with a suitable carrier or excipient. Preferably, the weight ratio of Tribulus terrestris, Turnera diffusa and Cinnamon cassia extracts is 2.5: 1.5: 0.2. Preferably, the Ginkgo biloba extract consists of a fraction of dimeric apigenin flavonoids, more preferably when the additional fraction of dimeric apigenin flavonoids is 50 mg. Preferably, the compositions according to the invention contain extracts of Tribulus terrestris, Turnera diffusa and Cinnamon cassia and L-arginine or L-arginine hydrochloride in a weight ratio of 1.5-3.5: 1-2: 0.1-0.4, respectively. : 0.5-1.5, more preferably when the weight ratio of Tribulus terrestris, Turnera diffusa and Cinnamon cassia extracts and L-arginine or L-arginine hydrochloride is 2.5 : 1.5 : 0.2 : 1. The subject of the invention it is also possible to use Tribulus terrestris, Turnera diffusa and Cinnamon cassia extracts in a weight ratio of 1.5-3.5: 1-2: 0.1-0.4, respectively, in combination with Ginkgo biloba extract and, optionally, arginine or its physiologically equivalent esters, salts or precursors, for the preparation of medicaments for the treatment of sexual dysfunction in men and women, and in particular for the treatment of impotence, erectile dysfunction, libido disorder, frigidity and lack of orgasm. Extracts of Tribulus terrestris, Turnera diffusa and Cinnamon cassia are known and have already been used for similar purposes in some types of traditional medicine, but they are not known in the composition, especially in the specific quantitative ratios mentioned above. In particular, it is known that Tribulus terrestris extract induces the synthesis of testosterone, a hormone responsible for stimulating the sexual drive in both men and women; Turnera diffus extract, rich in essential oils, has a vasodilatory effect through the release of NO, as a result of which the extract has a vasomotor effect on arteries and arteries; Cinnamon cassia extract indirectly stimulates libido by acting on dopamine receptors related to the feeling of pleasure. Finally, the strong anti-phosphodiesterase activity of dimeric flavones extracted from Ginkgo biloba contributes to the dilation of the corpora cavernosa vessels, consequently enhancing the vascular effects of Turner diffus. However, the therapeutic results obtained with the compositions according to the invention cannot be explained solely on the basis of the action of the individual extracts; in fact, it has surprisingly been found that when the extracts are combined in quantitative ratios other than those given above, they remain inactive and may even cause the disorder to worsen. Therefore, a real increase in sexual activity can only be achieved by using extracts of these plants in a precisely defined ratio, which increases both libido and blood supply to the genital organs. For the purposes of the invention, extracts of medicinal plants obtained by conventional techniques such as extraction with solvents or supercritical fluids may be used. However, it is advantageous to use standardized extracts with a specific content of certain characteristic extract components: for example, a Tribulus terrestris extract will contain approximately 40% of saponins expressed as dioscin; the Turnera diffusa extract is preferably a lipophilic extract; Ginkgo biloba extract preferably contains dimeric flavones in an amount of about 60%; and the Cinnamon cassia extract preferably contains approximately 70% cinnamaldehyde. Different parts of plants are used to prepare extracts, as they contain active ingredients in different concentrations. In particular, the whole plant is used for the preparation of Turnera diffus extracts, preferably extracted with carbon dioxide under supercritical conditions at a pressure between 230 and 250 bar, preferably 240 bar and at a temperature between 35 and 55° C, preferably 40°C; Tribulus terrestris extracts are preferably obtained from the above-ground parts and seeds of plants by extraction with a 40% ethanol/water mixture, while Cinnamon cassia extracts are preferably prepared by extracting the bark of the trunk with carbon dioxide under supercritical pressure conditions. between 110 and 150 bar, preferably 135 bar, at 35°C. Ginkgo biloba extract is preferably produced from a fraction containing dimeric flavonoids derived from apigenin, produced e.g. according to EP 360556. The mixture of extracts according to the invention should be taken for a long time, not only immediately before sexual intercourse, although in some patients the response to the drug occurs already after the first dose, within 30 minutes after taking the drug. Administration of the composition according to the invention even for a long time does not cause any significant side effects, is well tolerated and does not disturb the delicate hormonal balance, especially the androgen/estrogen balance, which determines the majority of male and female physiological processes such as andropause and menopause. Examples of suitable forms of administration of the compositions according to the invention include tablets, soft and hard gelatin capsules, suppositories and drinking preparations containing unit doses of Tribulus terrestris extract ranging between 100 and 300 mg and unit doses of the remaining ingredients in accordance with the weight ratio specified above. Solid preparations such as unmodified release or gastric acid resistant tablets or liquid drinking forms are particularly preferred. The following examples are given to illustrate the invention.PL 203 555 B1 4 EXAMPLE 1 - Preparation of coated tablets Each 700 mg film-coated tablet contains: Tribulus terrestris 250.00 mg Turnera diffusa 150.00 mg Cinnamon cassia 20.00 mg Ginkgo biloba 50.00 mg L-arginine 100.00 mg soy polysaccharides 55.00 mg silicon dioxide 14.00 mg silicified microcrystalline cellulose 42.00 mg magnesium stearate 4.00 mg hydroxypropylmethylcellulose 6.40 mg talc 5.20 mg titanium dioxide 2 .00 mg glycerin 0.12 mg Polysorbate 80 0.80 mg quinoline 0.43 mg indigo carmine 0.05 mg Example 2 - Preparation of hard gelatin drug capsules Each 340 mg capsule contains: Tribulus terrestris 125.00 mg Turnera diffusa 75 .00 mg Cinnamon cassia 10.00 mg Ginkgo biloba 25.00 mg L-arginine 50.00 mg soy polysaccharides 25.00 mg silicon dioxide 7.00 mg silicified microcrystalline cellulose 20.00 mg magnesium stearate 1.50 mg talc 1, 50 mg Example 3 - Preparation of soft gelatin capsules Each 700 mg soft gelatin capsule contains: Tribulus terrestris 125.00 mg Turnera diffusa 75.00 mg Cinnamon cassia 10.00 mg Ginkgo biloba 25.00 mg L-arginine 50.00 mg soy lecithin 20.00 mg medium chain triglycerides 100.00 mg Polysorbate 80 10.00 mg soybean oil 275.00 mg colloidal silicon dioxide 10.00 mg Example 4 - Preparation of drinking solution Each 10 ml vial contains: Tribulus terrestris 250.00 mg Turnera diffusa 150.00 mg Cinnamon cassia 20.00 mg Ginkgo biloba 50.00 mg L-arginine hydrochloride 100.00 mg glycerin 3000.00 mg Polysorbate 20 800.00 mg propylene glycol 1000.00 mg Acesulfame K 175.00 mg saccharin sodium 40.00 mgPL 203 555 B1 5 neohesperidin DC 2.50 mg flavors 300.00 mg potassium sorbate 11.70 mg methylparaben 8.30 mg purified water q.s. up to 10.00 ml Example 5 - Preparation of soluble granules Each 5000 mg sachet contains: Tribulus terrestris 250.00 mg Turnera diffusa 150.00 mg Cinnamon cassia 20.00 mg Ginkgo biloba 50.00 mg L-arginine hydrochloride 100.00 mg Polysorbate 20 500.00 mg Acesulfame K 175.00 mg sodium saccharin 40.00 mg neohesperidin DC 2.50 mg flavors 300.00 mg inulin 1000.00 mg mannitol 2412.50 mg PL PL PL
Claims (8)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI2002A000990 | 2002-05-10 | ||
| IT2002MI000990A ITMI20020990A1 (en) | 2002-05-10 | 2002-05-10 | USEFUL FORMULATIONS IN THE TREATMENT OF MALE AND FEMALE IMPOTENCE |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL371674A1 PL371674A1 (en) | 2005-06-27 |
| PL203555B1 true PL203555B1 (en) | 2009-10-30 |
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