DE202023002046U1 - The prophylaxis of cardiovascular problems such as aggregation of platelets and arteriosclerosis as well as bone loss and the reduction of libido in older men through the combined administration of the plant estrogen 8-prenylnaringenin with acetyl-salicylic acid - Google Patents
The prophylaxis of cardiovascular problems such as aggregation of platelets and arteriosclerosis as well as bone loss and the reduction of libido in older men through the combined administration of the plant estrogen 8-prenylnaringenin with acetyl-salicylic acid Download PDFInfo
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- 206010065687 Bone loss Diseases 0.000 title claims abstract description 7
- LPEPZZAVFJPLNZ-SFHVURJKSA-N sophoraflavanone B Chemical compound C1([C@@H]2CC(=O)C=3C(O)=CC(O)=C(C=3O2)CC=C(C)C)=CC=C(O)C=C1 LPEPZZAVFJPLNZ-SFHVURJKSA-N 0.000 title description 81
- YHWNASRGLKJRJJ-UHFFFAOYSA-N sophoraflavanone B Natural products C1C(=O)C2=C(O)C(CC=C(C)C)=C(O)C=C2OC1C1=CC=C(O)C=C1 YHWNASRGLKJRJJ-UHFFFAOYSA-N 0.000 title description 40
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- OIALAIQRYISUEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]e Polymers CCCCCCCCCCCCCCCCCC(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO OIALAIQRYISUEV-UHFFFAOYSA-N 0.000 description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
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- -1 Granulac 200 Chemical compound 0.000 description 2
- 206010024421 Libido increased Diseases 0.000 description 2
- 206010030247 Oestrogen deficiency Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BUHVIAUBTBOHAG-FOYDDCNASA-N (2r,3r,4s,5r)-2-[6-[[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound COC1=CC(OC)=CC(C(CNC=2C=3N=CN(C=3N=CN=2)[C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)C=2C(=CC=CC=2)C)=C1 BUHVIAUBTBOHAG-FOYDDCNASA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
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- OWYWGLHRNBIFJP-UHFFFAOYSA-N Ipazine Chemical compound CCN(CC)C1=NC(Cl)=NC(NC(C)C)=N1 OWYWGLHRNBIFJP-UHFFFAOYSA-N 0.000 description 1
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- 206010067572 Oestrogenic effect Diseases 0.000 description 1
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- 210000000941 bile Anatomy 0.000 description 1
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- 229940035811 conjugated estrogen Drugs 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
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- 238000011552 rat model Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Abstract
Eine Darreichungsform mit 8-PN in Kombination mit ASS zur peroralen Applikation zum Ausgleich des Alters-bedingten Verlustes eines Teils der E2-Produktion beim Mann ab dem 60ten Lebensjahr, wobei durch die Substitution mit 8-PN eine anti-arteriosklerotische Wirkung, eine wieder gesteigerte Libido und eine Hemmung des Knochensubstanzverlustes erreicht wird. Durch die Kombination mit niedrig dosiertem ASS wird zusätzlich eine Thromboseprophylaxe sichergestellt.A dosage form with 8-PN in combination with ASA for oral administration to compensate for the age-related loss of part of E2 production in men from the age of 60, with the substitution with 8-PN increasing the anti-arteriosclerotic effect Libido and an inhibition of bone loss is achieved. The combination with low-dose ASA also ensures thrombosis prophylaxis.
Description
ZusammenfassungSummary
Zu Zeit besitzen hochdosierte Estrogengaben zur Behandlung oder Prophylaxe von HK- oder anderen Erkrankungen des Mannes keine ausreichende wissenschaftliche Basis. Allerdings gibt es zwei jüngere klinische Studien, die das Absinken der endogenen E2-Spiegel ab 60 Jahren auf 30 % bestimmen, was einem Substitutionsbedarf von 10-20µg/d entspricht. Dieser Bedarf kann durch eine orale 8-PN Dosis von 100-200µg gedeckt werden. Die Tagesdosis entspricht einem halben bzw. einem Liter gehopften Bier. Es kann davon ausgegangen werden, dass durch die Behandlung u.a. eine anti-arteriosklerotische Wirkung, eine wieder gesteigerte Libido und eine Hemmung des Knochensubstanzverlustes erreicht wird. Diese positiven Wirkungen sollen ergänzt werden durch die Hemmung der Thrombozytenaggregation durch eine niedrige Dosis ASS. Das Präparat ist ausschließlich bei Männern anzuwenden, die ein erhöhtes Risiko für Thrombosen besitzen.There is currently no sufficient scientific basis for high-dose estrogen administration for the treatment or prophylaxis of HD or other diseases in men. However, there are two recent clinical studies that determine the decline in endogenous E2 levels from the age of 60 to 30%, which corresponds to a substitution requirement of 10-20µg/d. This requirement can be met by an oral 8-PN dose of 100-200µg. The daily dose corresponds to half or one liter of hopped beer. It can be assumed that the treatment will, among other things, achieve an anti-arteriosclerotic effect, an increased libido and an inhibition of bone loss. These positive effects should be complemented by the inhibition of platelet aggregation by a low dose of ASA. The preparation should only be used in men who have an increased risk of thrombosis.
HauptanspruchMain claim
Eine orale Darreichungsform von 8-PN zur prophylaktischen Verhinderung oder Abmilderung altersbedingter Erscheinungen. Insbesondere kann eine anti-arteriosklerotische Wirkung, eine wieder gesteigerte Libido und eine Hemmung des Knochensubstanzverlustes erreicht werden. 8-PN wird in Kombination mit ASS für Männer mit einem erhöhten Thromboserisiko entwickelt.An oral dosage form of 8-PN for the prophylactic prevention or alleviation of age-related symptoms. In particular, an anti-arteriosclerotic effect, increased libido and inhibition of bone loss can be achieved. 8-PN is being developed in combination with ASA for men with an increased risk of thrombosis.
BeschreibungDescription
Die Bedeutung einer ausreichend hohen und stabilen estrogenen Wirkung beim Mann ist bis heute Gegenstand intensiver Forschung und kontroverser Ergebnisse. In einer Übersichtsarbeit von 2004 (Dtsch Arztebl 2004; 101(9): A-578 / B-479 / C-471 Jockenhövel, Friedrich; Lehnert, Hendrik) werden die Ergebnisse einer Reihe von Studien in die verschiedenen Therapiegebiete eingeordnet und diskutiert. Alle zitierten Studien verwendeten hoch dosierte Estrogene, entweder E2, E3 oder konjugierte Estrogene. Im Ergebnis rieten die Autoren von der Verwendung von hochdosierten Estrogenen als Therapeutika insgesamt ab.The importance of a sufficiently high and stable estrogenic effect in men is still the subject of intensive research and controversial results. In a review from 2004 (Dtsch Ärztebl 2004; 101(9): A-578 / B-479 / C-471 Jockenhövel, Friedrich; Lehnert, Hendrik), the results of a number of studies are classified and discussed in the various therapeutic areas. All studies cited used high-dose estrogens, either E2, E3, or conjugated estrogens. As a result, the authors recommended against the use of high-dose estrogens as therapeutic agents altogether.
Dabei ist interessant, dass verschiedene (auch größere) Studien unterschiedliche Ergebnisse zeitigten. So wurden in einer frühen Studie keine Unterschiede in den Estradiolspiegeln mit dem fortschreitenden Alter gezeigt, in neueren Studien aber eine Absenkung der E2-Spiegel um 30% ab einem Lebensalter von 60 Jahren nachgewiesen. Damit ist die Basis der Intervention bereitet, wobei das Ziel lediglich ist, der E2-Absenkung entgegenzuwirken.It is interesting that different (including larger) studies produced different results. An early study showed no differences in estradiol levels with advancing age, but more recent studies demonstrated a reduction in E2 levels by 30% from the age of 60. This prepares the basis for the intervention, whereby the aim is simply to counteract the E2 reduction.
Ausgehend von einer täglichen Produktion von 70µg E2 bei jungen Männern (Documenta Geigy, Wiss. Tabellen 1975) oder 30µg/d (
Gegenstand der vorliegenden Anmeldung ist die systemische Anwendung des bislang bekannten potentesten pflanzlichen Estrogens, dem 8-Prenylnaringenin (8-PN) zur Ergänzung des Alters-bedingten Verlustes an E2 bei älteren Männern. 8-PN ist ein reines Estrogen, das an beide Rezeptoren (ERα,β) bindet. Dabei ist die Bindungsstärke an den ERα etwa doppelt so hoch wie an den ERß. Die Wirkstärke im Vergleich zum stärksten Estrogen, dem Estradiol (E2), beträgt etwa 1 (E2) zu 0.014 (8-PN). 8-PN ist also 70 mal weniger wirksam als E2. Untersuchungen am Modell der ovarektomierten Ratte haben gezeigt, dass 8-PN -anders als E2 - den Knochenabbau ohne einen trophischen Effekt auf den Uterus verhindert. Dieser Effekt beweist die Wirksamkeit von 8-PN in der Protektion des Knochensubstabbaus, der auch beim Mann durch E2 gesteuert wird. Auch die Restitution einer verringerten Libido wurde im Tiermodell und bei Männern nachgewiesen. Weiterhin wurde im Tiermodell ein protektives Profil für die Arteriosklerose gezeigt. Die Autoren schreiben als Resume:
- Taken together, 8-PN displays an anti-arterioscleroticprofile that appears to be even more beneficial than the one displayed by E2B as 8-PNtreatment did not decrease HDL levels nor rise TG serum concentrations. Thus, 8-PNdisplays a remarkable potential for the prevention of CVD associated with estrogen deficiency.
- Taken together, 8-PN displays an anti-arteriosclerotic profile that appears to be even more beneficial than the one displayed by E2B as 8-PNtreatment did not decrease HDL levels nor increase TG serum concentrations. Thus, 8-PNdisplays a remarkable potential for the prevention of CVD associated with estrogen deficiency.
Die positiven prophylaktischen Eigenschaften des 8-PN sollen mit der Thrombose-Prophylaxe durch niedrig dosiertes ASS kombiniert werden.The positive prophylactic properties of 8-PN should be combined with thrombosis prophylaxis using low-dose aspirin.
BeispieleExamples
1. 8-PN Kapselformulierung mit verzögerter Freisetzung und zusätzlicher Gabe von 100 mg Acetylsalicylsäure (ASS)1. 8-PN sustained release capsule formulation with additional administration of 100 mg acetylsalicylic acid (ASA)
Herstellung einer Matrixformulierung mit modifizierter Freisetzung mit 200 µg 8-PN und 100 mg ASS zur oralen Anwendung
- A: Herstellung einer Pulvermischung: In einem ersten Schritt wurden 200 mg 8-PN (60 - 100 U.S. Mesh, Sigma Aldrich), 100g ASS mit 346,8 g Hydroxypropylmethylcellulose (HPMC, z. B. RetaLac, Meggle) in einem geeigneten Turbula-Mischer (Bachhoven, Basel) für 15 Minuten gemischt. Der Mischung wurden 3 g Mg-Stearat zugesetzt und eine weitere Minute lang gemischt.
- B: Tablettierung: Zur Herstellung von Tabletten mit einem Gesamtgewicht von 450 mg und einer Härte von 50-60 N wurde eine geeignete Tablettenpresse (Korsch, Berlin) verwendet, die mit Flachstempeln und geeignetem Durchmesser (z. B. 11,3 mm) ausgestattet war.
- C: Auflösungstest: Der Test der 8-PN MR-Formulierung wurde gemäß USP XXIV, Gerät 2 (Paddelmethode, 50 U/min) mit 900 ml einer wässrigen 1%igen 17ß HPCD Lösung, äquilibriert auf 37 °C, durchgeführt. Die Konzentration von 8-PN im Auflösungsmedium wurde durch eine validierte HPLC-Methode mit UV-Detektion bestimmt.
- A: Preparation of a powder mixture: In a first step, 200 mg 8-PN (60 - 100 US Mesh, Sigma Aldrich), 100 g ASS with 346.8 g hydroxypropylmethylcellulose (HPMC, e.g. RetaLac, Meggle) were mixed in a suitable turbula -Mixer (Bachhoven, Basel) mixed for 15 minutes. 3 g of Mg stearate were added to the mixture and mixed for an additional minute.
- B: Tableting: A suitable tablet press (Korsch, Berlin) equipped with flat punches and a suitable diameter (e.g. 11.3 mm) was used to produce tablets with a total weight of 450 mg and a hardness of 50-60 N was.
- C: Dissolution test: The test of the 8-PN MR formulation was carried out according to USP XXIV, device 2 (paddle method, 50 rpm) with 900 ml of an aqueous 1% 17ß HPCD solution equilibrated at 37 ° C. The concentration of 8-PN in the dissolution medium was determined by a validated HPLC method with UV detection.
Die Testtabletten zeigen eine mittlere Auflösungsrate (aufgelöste Fraktion) von 20-30 % der deklarierten Dosis 8-PN nach 30 Minuten nach Beginn des Auflösungstests, 50-60 % nach 120 Minuten und 80-90 % nach 300 Minuten nach Beginn des Test Verfahrens.The test tablets show a mean dissolution rate (dissolved fraction) of 20-30% of the declared dose of 8-PN after 30 minutes after the start of the dissolution test, 50-60% after 120 minutes and 80-90% after 300 minutes after the start of the test procedure.
2. 8-PN Tablettenformulierung mit schneller Freisetzung und zusätzlicher Gabe von 100 mg Acetylsalicylsäure (ASS)2. 8-PN rapid release tablet formulation with additional administration of 100 mg acetylsalicylic acid (ASA)
Herstellung einer Tablette mit 200 µg 8-PN mit schneller Freisetzung des Wirkstoffs zur oralen Anwendung. A: Herstellung der Pressmasse: in einen geeigneten Mischer werden 0,2 g 8-PN (mikronisiert, 20.000 cm2/g, Blaine), 100 g Acetylsalicylsäure mit 150 g α-Lactosemonohydrat (z. B. Granulac 200, Meggle), 48 g mikrokristalline Cellulose (Avicel PH 101, BASF) und 1,4 g Croscarmellose Na gemischt. Anschließend wird der homogenen Mischung 0,4 g Mg Stearat als äußere Phase vorsichtig zugemischt. B: Tablettierung: Die Pressmasse nach A. wir auf einer geeigneten Tablettenpresse (Korsch) zu Tabletten mit 300 mg (d= 7 mm) verpresst. Die Qualität wird fortlaufend bzgl. Gewicht, Abrieb und Härte durch geeignete Prüfgeräte (Sotax n. Schleuniger) sichergestellt. Die Freisetzung von 8-PN wird mittels in vitro Dissolution Test (ERWEKA) in dest. Wasser bei 37 °C geprüft und ergibt bei 50 RPM eine Freisetzung von >75% der Dosis nach 30 min.Preparation of a tablet containing 200 µg 8-PN with rapid release of the active ingredient for oral use. A: Preparation of the molding compound: 0.2 g of 8-PN (micronized, 20,000 cm 2 /g, Blaine), 100 g of acetylsalicylic acid with 150 g of α-lactose monohydrate (e.g. Granulac 200, Meggle) are added to a suitable mixer. 48 g microcrystalline cellulose (Avicel PH 101, BASF) and 1.4 g Croscarmellose Na mixed. 0.4 g of Mg stearate is then carefully mixed into the homogeneous mixture as an external phase. B: Tableting: The pressing compound according to A. is pressed into tablets with 300 mg (d = 7 mm) on a suitable tablet press (Korsch). The quality is continuously ensured with regard to weight, abrasion and hardness using suitable testing devices (Sotax n. Schleuniger). The release of 8-PN is determined using the in vitro dissolution test (ERWEKA) in distilled water. Water tested at 37 °C and at 50 RPM results in a release of >75% of the dose after 30 min.
3. Wässrige Lösung von 8-PN zur oralen Anwendung3. Aqueous solution of 8-PN for oral use
Herstellung einer wässrigen Lösung zur oralen Anwendung von 150µg 8-PN.
- A: Herstellung eines Granulats: in einen geeigneten Mischer werden 0,15 g 8-PN (mikronisiert, 20.000 cm2/g, Blaine) mit 5 g 17ß Hydroxypropylcyclodextrin und 493,35 g α-Lactosemonohydrat (z. B. Granulac 200, Meggle) und 1,5 g Erythritol Stevia gemischt. Die homogene Mischung wird portionsweise zu 0,5 g in Sachets (Zweirand- oder Vierrandbtl.) abgefüllt und versiegelt.
- B: Herstellung der Lösung: ein Sachet wird geöffnet und der Inhalt in 100 ml Trinkwasser unter Rühren zur Auflösung gebracht und oral verabreicht.
- A: Production of a granulate: 0.15 g of 8-PN (micronized, 20,000 cm 2 /g, Blaine) with 5 g of 17ß hydroxypropylcyclodextrin and 493.35 g of α-lactose monohydrate (e.g. Granulac 200, Meggle) and 1.5 g erythritol stevia mixed. The homogeneous mixture is filled in portions of 0.5 g into sachets (two-edged or four-edged bags) and sealed.
- B: Preparation of the solution: a sachet is opened and the contents are dissolved in 100 ml of drinking water with stirring and administered orally.
4. Wässrige Suspension von 8-PN zur Oralen Applikation.4. Aqueous suspension of 8-PN for oral administration.
10 mg 8-PN (mikronisiert, 20.000 cm2/g, Blaine) wird gewogen und in einem geeigneten Mischgerät schrittweise mit einer wässrigen Lösung aus 0,9% Natriumchlorid, 0,085% Polyoxyethylen-50-stearat (Myrj53) und 1,0% Hydroxypropyl cellulose 75000 (Klucel LF) als Trägerlösung versetzt bis eine homogene Suspension entsteht. Das Volumen wird mit der Trägerlösung bis zu einem Endvolumen von 500ml aufgefüllt und durch vorsichtiges Schütteln homogenisiert. Danach wird die Suspension portionsweise zu je 10 ml entsprechend 200 µg 8-PN/Dosis in geeignete Abgabegefäße abgefüllt und verschlossen10 mg of 8-PN (micronized, 20,000 cm 2 /g, Blaine) is weighed and mixed in a suitable mixing device stepwise with an aqueous solution of 0.9% sodium chloride, 0.085% polyoxyethylene 50 stearate (Myrj53) and 1.0% Hydroxypropyl cellulose 75000 (Klucel LF) is added as a carrier solution until a homogeneous suspension is formed. The volume is filled up with the carrier solution to a final volume of 500ml and homogenized by careful shaking. The suspension is then filled into suitable dispensing containers in portions of 10 ml each corresponding to 200 µg 8-PN/dose and sealed
ZITATE ENTHALTEN IN DER BESCHREIBUNGQUOTES INCLUDED IN THE DESCRIPTION
Diese Liste der vom Anmelder aufgeführten Dokumente wurde automatisiert erzeugt und ist ausschließlich zur besseren Information des Lesers aufgenommen. Die Liste ist nicht Bestandteil der deutschen Patent- bzw. Gebrauchsmusteranmeldung. Das DPMA übernimmt keinerlei Haftung für etwaige Fehler oder Auslassungen.This list of documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.
Zitierte Nicht-PatentliteraturNon-patent literature cited
- Nocke-Fink und Breuer Z. Klin. Chem. Klin. Biochcm. 10. Jg. 1972, S. 395-402 [0005]Nocke-Fink and Breuer Z. Klin. Chem. Klin. Biochcm. 10th year 1972, pp. 395-402 [0005]
- Effects of long-term treatment with 8-prenylnaringenin and oral estradiol on the GH-IGF-1 axis and lipid metabolism in rats Martina Böttner, Julie Christoffel and Wolfgang Wuttke; Journal of Endocrinology (2008) 198, 395-401 [0006]Effects of long-term treatment with 8-prenylnaringenin and oral estradiol on the GH-IGF-1 axis and lipid metabolism in rats Martina Böttner, Julie Christoffel and Wolfgang Wuttke; Journal of Endocrinology (2008) 198, 395-401 [0006]
Claims (10)
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| DE202023002046.8U DE202023002046U1 (en) | 2023-09-28 | 2023-09-28 | The prophylaxis of cardiovascular problems such as aggregation of platelets and arteriosclerosis as well as bone loss and the reduction of libido in older men through the combined administration of the plant estrogen 8-prenylnaringenin with acetyl-salicylic acid |
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| DE202023002046.8U DE202023002046U1 (en) | 2023-09-28 | 2023-09-28 | The prophylaxis of cardiovascular problems such as aggregation of platelets and arteriosclerosis as well as bone loss and the reduction of libido in older men through the combined administration of the plant estrogen 8-prenylnaringenin with acetyl-salicylic acid |
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Non-Patent Citations (2)
| Title |
|---|
| Effects of long-term treatment with 8-prenylnaringenin and oral estradiol on the GH-IGF-1 axis and lipid metabolism in rats Martina Böttner, Julie Christoffel and Wolfgang Wuttke; Journal of Endocrinology (2008) 198, 395-401 |
| Nocke-Fink und Breuer Z. Klin. Chem. Klin. Biochcm. 10. Jg. 1972, S. 395-402 |
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