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WO2010077723A1 - Procédé de traitement d'une nycturie - Google Patents

Procédé de traitement d'une nycturie Download PDF

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Publication number
WO2010077723A1
WO2010077723A1 PCT/US2009/067290 US2009067290W WO2010077723A1 WO 2010077723 A1 WO2010077723 A1 WO 2010077723A1 US 2009067290 W US2009067290 W US 2009067290W WO 2010077723 A1 WO2010077723 A1 WO 2010077723A1
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Prior art keywords
bismuth
bph
patient
alpha
nocturia
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English (en)
Inventor
John F. Hauck
Gordon Hisashi Sato
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    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/29—Antimony or bismuth compounds

Definitions

  • the present disclosure relates to a method of treating and preventing nocturia, and more particularly to a method of using bismuth compounds to treat nocturia.
  • Nocturia is a medical condition that results in the need to wake up one or more times during the night to urinate.
  • One common form of nocturia is normally associated with pregnancy. This form progresses in severity with the pregnancy, but usually disappears completely after birth.
  • Nocturia may also be symptomatic of a variety of medical conditions including infection of the bladder, kidney, or urinary tract, as well as diabetes, congestive heart failure, kidney failure, sleep apnea, and/or enlargement of the prostate gland.
  • the prostate gland is a walnut sized exocrine gland that functions to make prostate fluid, the most abundant component of semen.
  • the prostate is located directly beneath the bladder and surrounds the upper region of the urethra, which serves as the conduit by which urine is emptied from the bladder.
  • the prostate is connected to the urethra of the bladder by a conduit known as the prostatic urethra, which allows prostate fluid to be injected into the urinary tract during ejaculation.
  • the prostate gland is divided into three general zones including a peripheral zone, a transitional zone, and a central zone. All three zones are encapsulated in a fibrous prostatic capsule.
  • the location of the prostate gland means that enlargement of the gland exerts direct effects on the bladder and the urethra, which may cause a variety of unpleasant lower urinary tract symptoms (LUTS).
  • LUTS may include nocturia, an increased sense of urinary urgency or frequency, a weak or hesitant urinary stream, difficulty initiating urination, and/or urethral occlusion, a serious medical condition which may lead to acute urinary retention.
  • Prostatitis is a clinical condition associated with infection and/or inflammation of the prostate that may affect men of any age.
  • BPH benign prostatic hyperplasia
  • Prostatitis is a clinical condition associated with infection and/or inflammation of the prostate that may affect men of any age.
  • BPH is a common cause of prostate enlargement in older men that occurs at statistically significant frequencies in the population, with nearly 50% of men in the age range of 51-60, 70% of men in the age range of 61-70, and 90% of men in the age range of 81-90 displaying histological manifestations of BPH.
  • BPH is believed to result from the renewal of developmental growth within the prostate gland.
  • the prostate gland grows from the size of a pea until it reaches its normal walnut size shortly after puberty. The size of the prostate gland then typically remains constant until sometime between the ages of 40 and 50, at which point it undergoes a second round of growth that typically results from the progressive hyperplasia of the stromal and glandular prostatic cells in the transitional zone of the prostate.
  • the constant size of the prostate gland between puberty and the mid-forties is believed to be maintained by a homeostatic process that balances cellular proliferation with cellular apoptosis.
  • This homeostasis is regulated by interactions between several key organs of the endocrine system including, the hypothalamus, the pituitary, and the testicles, which ultimately control the production of androgens (male sex hormones), including testosterone.
  • Testosterone plays a key role in regulating the growth of the prostate. Most circulating testosterone is found in the blood complexed with carrier molecules (e.g. albumin or sex hormone binding globulin); however, a small percentage (-3%) of testosterone circulates in free (un-bound ) form. Free testosterone is able to pass through the cell membranes of prostate cells, where it is metabolized by 5 -alpha reductase (5- ⁇ R) into dihydrotestosterone (DHT), an extremely potent male sex hormone. DHT binds to androgen receptors (AR) within the glandular cells of the transitional zone of the prostate gland, and DHT/ AR complexes translocate across the nuclear membrane and function as transcriptional activators to initiate transcription profiles that result in cellular proliferation.
  • carrier molecules e.g. albumin or sex hormone binding globulin
  • DHT dihydrotestosterone
  • the LUTS associated with prostate enlargement can negatively affect the quality of life of men in a variety of ways. For example, daytime frequency and urgency symptoms may disrupt normal daily activities. Additionally, nocturia may severely disrupt an individual's normal sleep cycle, resulting in sleep deprivation and chronic fatigue. Generally, two approaches have been taken to deal with the LUTS that stem from prostate enlargement: medicinal and surgical.
  • Medicinal therapies typically employ, singularly or in combination, drugs that either block the alpha- 1 adrenergic receptor ( ⁇ -1 AR) or inhibit the activity of 5- ⁇ R.
  • ⁇ -1 AR alpha- 1 adrenergic receptor
  • One mode of action of the ⁇ -1 AR is to stimulate contraction of the smooth muscle of the prostate gland, upper urethra, and bladder, which has the effect of enhancing LUTS like hesitancy, urgency, and urinary obstruction or reduced urinary flow.
  • Drugs that function as ⁇ -1 AR blockers include, but are not limited to, tamsulosin (Flomax®), alfuzosin (Uroxatral®), silodosin (Urief®), terazosin (Hytrin®), and doxazosin (Cardura®).
  • ⁇ -1 AR blockers relieve many of the LUTS associated with prostate enlargement by relaxing the smooth muscle tissue of the prostate, urethra, and bladder.
  • many ⁇ -1 AR blockers function as vasodilators and may cause hypotensive side effects that stem from lowered blood pressure levels.
  • a further disadvantage is that some ⁇ -1 AR blockers display negative interactions with commonly prescribed drugs, for example, non-steroidal anti-inflammatory drugs, enalapril, and verapamil.
  • 5- ⁇ R inhibitors prevent the conversion of testosterone to DHT, thereby preventing further enlargement of the prostate.
  • Drugs that function as 5- ⁇ R inhibitors include, but are not limited to, finasteride (Proscar®) and dutasteride (Avodart®).
  • 5- ⁇ R inhibitors have significant sexual side effects including, but not limited to, lowered sex drive, ejaculatory dysfunction, and erectile dysfunction.
  • Surgical therapies focus on methods of physically reducing the size of the prostate.
  • These therapies are designed to remove some portion, or all, of the prostate and include, but are not limited to, open prostatectomy, transurethral resection of the prostate, transurethral microwave thermotherapy, transurethral needle ablation, and laser prostatectomy.
  • surgical therapies are subject to the many risks that are normally associated with surgery.
  • a further disadvantage associated with surgical therapies is that they may be associated with serious sexual side effects including, but not limited to, sterility and retrograde ejaculation.
  • bismuth-containing compounds may be employed for reducing the urinary frequency commonly associated with nocturia in men. Without being bound by any particular theory, it is believed that the observed positive effects of bismuth-containing compounds on nocturia in men stem from their ability to counteract the effects of prostate enlargement on the lower urinary tract (e.g. proximal urethra and bladder).
  • the present disclosure relates to a method of using bismuth-containing compounds to reduce the LUTS associated with prostate enlargement due to prostatitis and benign prostatic hyperplasia (BPH), for example, nocturia.
  • Preferred bismuth-containing compounds are bismuth subcitrate, bismuth subsalicylate, and mixtures thereof, with bismuth subsalicylate being the most preferred.
  • the present disclosure further relates to a method of administering bismuth- containing compounds, separately, sequentially or simultaneously in separate or combined pharmaceutical formulations with a second BPH-active agent.
  • Preferred secondary BPH- active agents include, but are not limited to, NSAIDs, alpha- 1 adreneric receptor blockers, and 5 alpha reductase inhibitors.
  • the present disclosure relates to bismuth-containing pharmaceutical compositions suitable for administration to humans and animals. More particularly, the present disclosure relates to methods of using such pharmaceutical compositions to treat nocturia that results from enlargement of the prostate gland.
  • the pharmaceutical compositions of the present disclosure comprise a bismuth- containing agent, preferably in the form of a pharmaceutically acceptable salt.
  • such bismuth-containing agents may include, but are not limited to, bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof.
  • Bismuth citrate, bismuth subcitrate, tripotassium dicitrato bismuthate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof are preferred bismuth salts for use in this disclosure. More preferred are bismuth subcitrate, bismuth subsalicylate, and mixtures thereof. Bismuth subsalicylate is most preferred.
  • bismuth-containing agents are well known in the art and are commercially available. Their formulation and use in commercial compositions are also well-known, for example, Pepto-Bismol® (containing bismuth subsalicylate; sold by The Procter & Gamble Company in a variety of formulations as an anti-diarrhea/nausea/upset stomach agent).
  • Pepto-Bismol® containing bismuth subsalicylate
  • a pharmaceutically acceptable carrier to be used in conjunction with the bismuth-containing agent is determined by the manner in which the composition is to be administered. It is contemplated within the scope of the disclosure that representative delivery regimens may include oral, parenteral (including subcutaneous, intramuscular, and intravenous), rectal, buccal, sublingual, pulmonary, transdermal, intranasal, and most preferably oral. Administration may be continuous or intermittent (e.g. by bolus injection).
  • the preferred mode of administering the compositions of the present disclosure is orally. Consequently, the preferred unit dosage form may be tablets, caplets, capsules, lozenges, dissolvable strips, liquids, and the like, comprising a safe and effective amount of the bismuth-containing agent of the present disclosure.
  • oral unit dosage forms like tablets and capsules may include, but are not limited to, chewable, prolonged dosage composition, and timed release formulations.
  • U.S. Patent No. 5,225,197 describes a chewable tablet that includes a medicament in a chewable base such as mannitol and an effervescent couple such as citric acid-sodium bicarbonate.
  • U.S. Patent No. 5,096,714 describes a prolonged dosage composition comprising a gel-forming dietary fiber, a biologically absorbable drug or other therapeutic agent, and certain disintegrants, namely, a physiologically acceptable edible acid and a mineral salt that release a physiologically acceptable gas upon ingestion.
  • compositions suitable for the preparation of unit dosage forms for oral administration are well known in the art. Their selection will depend on secondary considerations like taste, cost, shelf stability, etc., which are not critical for the purposes of the present disclosure, and can be easily made by one of ordinary skill in the art.
  • the pharmaceutically-acceptable carrier employed in conjunction with the bismuth- containing agent of the present disclosure is used at a concentration sufficient to provide a practical mass to dosage relationship.
  • the pharmaceutically acceptable carriers in total, may comprise from about 0.1% to about 99.9%, by weight, of the pharmaceutical compositions of the present disclosure, preferably from about 20% to about 99.8%, and most preferably from about 30% to about 90%.
  • the methods of the present disclosure typically involve administering the bismuth- containing agent in an amount of from about 5 mg to about 5000 mg of bismuth per day.
  • the quantity of the bismuth-containing agents to be administered is indicated by the weight of bismuth present in the dose of the bismuth-containing agent. Therefore, the actual weight of a dose of a bismuth-containing agent will be greater than the amount of bismuth indicated. It is contemplated within the scope of the disclosure that from about 50 mg to about 2000 mg of bismuth are administered per day, and more preferably from about 100 mg to about 400 mg.
  • a variety of pharmaceutically-acceptable carriers may be included, depending on the particular dosage form to be used.
  • Various oral dosage forms may be used, including such solid forms as tablets, capsules, granules, bulk powders, and the like. Tablets may be compressed, tablet triturates, enteric-coated, sugar-coated, film-coated, multiple compressed, or the like, containing suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, melting agents, and the like.
  • Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, melting agents, coloring, flavoring agents, and the like.
  • Liquid oral compositions typically comprise water and suspending agents, such as magnesium aluminum silicate and the like, as part of the pharmaceutically acceptable carrier.
  • substances that may serve as pharmaceutically acceptably carriers are sugars (e.g. lactose, glucose, sucrose, and the like), starches (e.g. corn starch, potato starch, and the like), cellulose and its derivatives (e.g. sodium carboxymethylcellulose, ethylcellulose, cellulose acetate, and the like), powdered tragacanth, malt, gelatin, talc, stearic acid, magnesium stearate, calcium sulfate, vegetable oils (e.g. peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, oil of theobroma, and the like); polyols (e.g.
  • propylene glycol propylene glycol, glycerine, sorbitol, mannitol, polyethylene glycol, and the like), agar, alginic acid, pyrogen- free water, isotonic saline, and phosphate buffer solutions, as well as other non-toxic compatible substances used in pharmaceutical formulations.
  • Wetting agents and lubricants such as sodium lauryl sulfate, as well as coloring agents, flavoring agents, excipients, tableting agents, stabilizers, anti-oxidants, preservatives, and the like may also be present.
  • Other compatible pharmaceutical additives and actives may be included in the pharmaceutically acceptable carrier for use in the compositions of the present disclosure.
  • a second BPH-active agent may be a therapeutically effective dosage of any of a variety of non-steroidal anti-inflammatory drugs (NSAIDs) belonging to the following classes of molecules: salicylates (e.g.
  • acetylsalicylic acid amoxiprin, benorylate, choline magnesium salicylate, diflunisal, ethenzamide, dispatchlamine, methyl salicylate, magnesium salicylate, salicyl salicylate, salicylamide, and the like
  • arylalkanoic acids e.g. aceclofenac, acemethacin, alclofenac, bromfenac, diclofenac, etodolac, indomethacin, nabumetone, oxametacin, proglumetacin, sulindac, tolmetin, and the like
  • 2-arylproprionic acids e.g.
  • NSAIDs may also include, but are not limited to, nimesulide, licofelone, and omega-3 fatty acids.
  • a second BPH-active agent may be a therapeutically effective dosage of any of a variety of alpha- 1 adreneric receptor blockers including, but not limited to, phenoxybenzamine, prazosin, terazosin, doxazosin, alfuzosin, fiduxosin, silodosin, AIO-8507L, pamirosin, tamsulosin, and the like.
  • a second BPH- active agent may be a therapeutically effective dosage of any of a variety of 5 alpha reductase inhibitors including, but not limited to, finasteride, dutasteride, isotretinoin, FCE 2860, and the like.
  • a second BPH- active agent may be a therapeutically effective dosage of any of the following compounds including, but not limited to, ACE, ML-04A, lonidamine, 1-o-m mcs, tadalafil, QLT0074, talaporfm sodium, sildenafil, ozarelix, degarelix, vardenafil, lemuteporfm, NX-1207, pomegranate, cetrorelix pamoate, UK-369003, and botulinum toxin type A.
  • combinations of a bismuth-containing agent with a second anti-BPH agent referred to above may conveniently be presented for use in the form of a pharmaceutical formulation.
  • the combination pharmaceutical formulations thus produced represent a further aspect of the disclosure. It is contemplated within the scope of the disclosure that the use of combinations of agents may reduce the therapeutically effective dose of each, or either, pharmaceutical composition in a mannerly that has the advantage of reducing any negative side effects it (or they) may have.
  • Dosage levels and time course of administration of the active ingredients in the pharmaceutical formulations of the invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.
  • This dosage may be delivered in a conventional pharmaceutical formulation by a single administration, by multiple applications, or via controlled release, as needed to achieve the most effective results, preferably once or twice daily (especially once daily), e.g., by mouth. In certain situations, alternate day dosing may prove adequate to achieve the desired therapeutic response.
  • the selection of the exact dose and formulation and the most appropriate delivery regimen will be influenced by the pharmacological properties of the formulation, the nature and severity of the condition being treated, and the physical condition and mental acuity of the recipient.
  • compositions may be prepared for parenteral (including subcutaneous, intramuscular, and intravenous), administration, particularly in the form of liquid solutions or suspensions, or for oral or buccal administration, particularly in the form of tablets or capsules, or for pulmonary or intranasal administration, particularly in the form of powders, nasal drops or aerosols, or for rectal, transdermal, or intra-glandular administration.
  • parenteral including subcutaneous, intramuscular, and intravenous
  • administration particularly in the form of liquid solutions or suspensions, or for oral or buccal administration, particularly in the form of tablets or capsules, or for pulmonary or intranasal administration, particularly in the form of powders, nasal drops or aerosols, or for rectal, transdermal, or intra-glandular administration.
  • parenteral including subcutaneous, intramuscular, and intravenous
  • administration particularly in the form of liquid solutions or suspensions
  • oral or buccal administration particularly in the form of tablets or capsules
  • pulmonary or intranasal administration particularly in the form of powder
  • Formulations for parenteral administration may contain as excipients sterile water or saline, alkylene glycols such as propylene glycol, polyalkylene glycols such as polyethylene glycol, oils of vegetable origin, hydrogenated naphthalenes and the like.
  • Formulations for nasal administration may be solid and may contain excipients, for example, lactose or dextran, or may be aqueous or oily solutions for use in the form of nasal drops or metered spray.
  • typical excipients include sugars, calcium stearate, magnesium stearate, pregelatinated starch, and the like.
  • Orally administrable compositions may comprise one or more physiologically compatible carriers and/or excipients and may be in solid or liquid form.
  • Tablets and capsules may be prepared with binding agents, for example, syrup, acacia, gelatin, sorbitol, tragacanth, or poly-vinylpyrollidone, and the like; fillers, such as lactose, sucrose, corn starch, calcium phosphate, sorbitol, glycine, or the like; lubricants, such as magnesium stearate, talc, polyethylene glycol, silica, or the like; and surfactants, such as sodium lauryl sulfate and the like.
  • binding agents for example, syrup, acacia, gelatin, sorbitol, tragacanth, or poly-vinylpyrollidone, and the like
  • fillers such as lactose, sucrose, corn starch, calcium phosphate, sorbitol, glycine, or the like
  • lubricants such as magnesium stearate, talc, polyethylene glycol, silica, or the like
  • surfactants
  • Liquid compositions may contain conventional additives such as suspending agents, for example sorbitol syrup, methyl cellulose, sugar syrup, gelatin, carboxymethylcellulose, edible fats, or the like; emulsifying agents such as lecithin, acacia, or the like; vegetable oils such as almond oil, coconut oil, cod liver oil, peanut oil, or the like; preservatives such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and the like.
  • Liquid compositions may be encapsulated in, for example, gelatin to provide a unit dosage form.
  • Preferred solid oral dosage forms include tablets, two piece hard shell capsules, and soft elastic gelatin (SEG) capsules.
  • SEG capsules are of particular interest because they provide distinct advantages over the other two forms (see Seager, H., "Soft gelatin capsules: a solution to many tableting problems"; Pharmaceutical Technology, 9, (1 985)).
  • SEG capsules may allow dose-content uniformity to be optimized because the drug is dissolved or dispersed in a liquid that can be dosed into the capsules accurately.
  • drugs formulated as SEG capsules may improve bioavailability because the drug is dissolved, solubilized, or dispersed in an aqueous-miscible or oily liquid; consequently, the solutions dissolve or are emulsified to produce drug dispersions of high surface area when released in the body.
  • SEG capsules may reduce the degradation of oxidation-sensitive drugs during storage because the dry shell of soft gelatin provides a barrier against oxygen diffusion.
  • the dry shell formulation typically comprises of about 40-60% concentration of gelatin, about a 20-30% concentration of plasticizer (such as glycerin, sorbitol, propylene glycol, or the like) and about a 30-40% concentration of water. Other materials such as preservatives, dyes, opacifiers, flavors, and the like may also be present.
  • the liquid fill material comprises a solid drug that has been dissolved, solubilized or dispersed (with suspending agents such as beeswax, hydrogenated castor oil, polyethylene glycol 4000, or the like) or a liquid drug in vehicles or combinations of vehicles such as mineral oil, vegetable oils, triglycerides, glycols, polyols, surface-active agents, and the like.
  • Subjects were then administered bismuth subsalicylate (USP Granular, American International Chemical, CAS # 14882-18-9) at varying doses to assess the effect on the baseline state of nocturia. Both subjects were initially tested using a single dose of about 130 mg of pure bismuth subsalicylate per day. Neither subject displayed an altered baseline of state of nocturia at this dose. Both subjects were then tested using a single dose of about 260 mg of pure bismuth subsalicylate per day. As shown in Table 2, Subject A displayed an approximately two fold drop in urination frequency during the night (from 4 to 2 times per night), while Subject B displayed an approximately 2.5 fold drop in frequency (from 2.7 to 1.1 times per night).
  • urine measurements obtained from both subjects revealed that the urinary volume about doubled during the course of bismuth subsalicylate administration. Additionally, both subjects reported that sensations of "urgency" were reduced during this period as well.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur un procédé d'utilisation de composés contenant du bismuth pour réduire des symptômes des voies urinaires inférieures associés à un agrandissement de la prostate dû à une prostatite et une hyperplasie prostatique bénigne (BPH), par exemple une nycturie. Les composés préférés contenant du bismuth sont le subcitrate de bismuth, le subsalicylate de bismuth et des mélanges de ceux-ci, avec le subsalicylate de bismuth qui est le composé préféré. L'invention porte en outre sur un procédé d'administration de composés contenant du bismuth, séparément, séquentiellement ou simultanément dans des formulations pharmaceutiques séparées ou combinées avec un second agent actif contre la BPH. Les agents actifs contre la BPH secondaire préférés comprennent, mais sans s'y limiter, des anti-inflammatoires non stéroïdiens (NSAID), des bloqueurs de récepteurs adrénergiques alpha 1 et des inhibiteurs de réductase alpha 5.
PCT/US2009/067290 2009-01-05 2009-12-09 Procédé de traitement d'une nycturie Ceased WO2010077723A1 (fr)

Applications Claiming Priority (2)

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US14244309P 2009-01-05 2009-01-05
US61/142,443 2009-01-05

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WO2010077723A1 true WO2010077723A1 (fr) 2010-07-08

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103360298A (zh) * 2012-04-06 2013-10-23 昆明积大制药股份有限公司 一种β型西洛多辛晶体的制备方法
ES2539425A1 (es) * 2015-03-30 2015-06-30 Enrique Blanxart Sena Composición farmacéutica para el tratamiento de la inflamación y/o agrandamiento de la próstata

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030180352A1 (en) * 1999-11-23 2003-09-25 Patel Mahesh V. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US20060204588A1 (en) * 2005-03-10 2006-09-14 Elan Pharma International Limited Formulations of a nanoparticulate finasteride, dutasteride or tamsulosin hydrochloride, and mixtures thereof
US20070093493A1 (en) * 2005-10-12 2007-04-26 Lilly Icos Llc Treatment of benign prostatic hypertrophy and lower urinary tract symptoms
US20080233183A1 (en) * 2007-03-22 2008-09-25 Pathfinder Management, Inc. Topical formulations having enhanced bioavailability

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030180352A1 (en) * 1999-11-23 2003-09-25 Patel Mahesh V. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US20060204588A1 (en) * 2005-03-10 2006-09-14 Elan Pharma International Limited Formulations of a nanoparticulate finasteride, dutasteride or tamsulosin hydrochloride, and mixtures thereof
US20070093493A1 (en) * 2005-10-12 2007-04-26 Lilly Icos Llc Treatment of benign prostatic hypertrophy and lower urinary tract symptoms
US20080233183A1 (en) * 2007-03-22 2008-09-25 Pathfinder Management, Inc. Topical formulations having enhanced bioavailability

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103360298A (zh) * 2012-04-06 2013-10-23 昆明积大制药股份有限公司 一种β型西洛多辛晶体的制备方法
ES2539425A1 (es) * 2015-03-30 2015-06-30 Enrique Blanxart Sena Composición farmacéutica para el tratamiento de la inflamación y/o agrandamiento de la próstata
WO2016156647A1 (fr) * 2015-03-30 2016-10-06 Enrique Blanxart Sena Composition pharmaceutique pour le traitement de l'inflammation et/ou de l'agrandissement de la prostate

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