USRE47316E1 - Oral formulations of ospemifene - Google Patents

Oral formulations of ospemifene Download PDF

Info

Publication number
USRE47316E1
USRE47316E1 US15/191,316 US201615191316A USRE47316E US RE47316 E1 USRE47316 E1 US RE47316E1 US 201615191316 A US201615191316 A US 201615191316A US RE47316 E USRE47316 E US RE47316E
Authority
US
United States
Prior art keywords
formulation
ospemifene
drug
pharmaceutically acceptable
drug formulation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active, expires
Application number
US15/191,316
Other languages
English (en)
Inventor
Veli-Matti Lehtola
Markku Anttila
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
QuatRx Pharmaceuticals Co
Original Assignee
QuatRx Pharmaceuticals Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US11/592,989 external-priority patent/US8758821B2/en
Application filed by QuatRx Pharmaceuticals Co filed Critical QuatRx Pharmaceuticals Co
Priority to US15/191,316 priority Critical patent/USRE47316E1/en
Assigned to DUCHESNAY INC. reassignment DUCHESNAY INC. MOVABLE HYPOTHEC Assignors: SHIONOGI INC.
Assigned to QUATRX PHARMACEUTICALS COMPANY reassignment QUATRX PHARMACEUTICALS COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HORMOS MEDICAL OY
Application granted granted Critical
Publication of USRE47316E1 publication Critical patent/USRE47316E1/en
Active legal-status Critical Current
Adjusted expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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
    • A61K31/075—Ethers or acetals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • 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
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • 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
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • 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
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Definitions

  • This invention relates to a liquid or semisolid oral drug formulation comprising ospemifene or a closely related compound as active ingredient.
  • SERM selective estrogen receptor modulators
  • the effects may be tissue-specific as in the case of tamoxifen and toremifene which have estrogen-like effects in the bone, partial estrogen-like effect in the uterus and liver, and pure antiestrogenic effect in breast cancer.
  • Raloxifene and droloxifen are similar to tamoxifen and toremifene, except that their antiestrogenic properties dominate. Based on the published information, many SERMs are more likely to cause menopausal symptoms than to prevent them.
  • Ospemifene is the Z-isomer of the compound of formula (I)
  • toremifene is known to be an estrogen agonist and antagonist (Kangas, 1990; International patent publications WO 96/07402 and WO 97/32574).
  • the compound is also called (deaminohydroxy)toremifene and it is also known under the code FC-1271a.
  • Ospemifene has relatively weak estrogenic and antiestrogenic effects in the classical hormonal tests (Kangas, 1990). It has anti-osteoporosis actions and it decreases total and LDL cholesterol levels in both experimental models and in human volunteers (International patent publications WO 96/07402 and WO 97/32574). It also has antitumor activity in an early stage of breast cancer development in an animal breast cancer model.
  • Ospemifene is also the first SERM which has been shown to have beneficial effects in climacteric syndromes in healthy women.
  • the published patent application WO 03/103649 describes the use of ospemifene for inhibition of atrophy and for the treatment or prevention of atrophy-related diseases or disorders in women, especially in women during or after the menopause.
  • An object of the present invention is to provide an improved drug formulation containing ospemifene, where the absorption of the drug is essentially increased and the variability in plasma level is essentially decreased.
  • the invention concerns a liquid or semisolid oral drug formulation comprising a therapeutically active compound of the formula (I)
  • FIG. 1 shows serum concentration of ospemifene versus time after a single dose of 60 mg ospemifene administered as a 60 mg tablet (circles), two hard gelatine 30 mg capsules (triangles) or a solution (stars).
  • liquid formulation refers here particularly to a solution, a suspension with solid particles dispersed in a liquid, an emulsion with liquid droplets dispersed in a liquid, or to a syrup.
  • semisolid formulation refers especially to gels and pastes.
  • the liquid drug formulation is a solution of compound I in a suitable carrier, which can be a single carrier or a mixture of several carriers.
  • the compounds of formula I have very low solubility in water.
  • the carrier shall therefore preferably comprise one or more lipophilic ingredients.
  • digestible lipids such as triglycerides, diglycerides, fatty acids, phospholipids, or the like instead of indigestible oils such as mineral oils (Porter and Charman, 2001).
  • a special group of useful carriers or ingredients therein may be cholane derivatives.
  • U.S. Pat. No. 4,117,121 disclosed a group of cholane derivatives useful to decrease cholesterol level and to increase bile flow.
  • the bioavailability enhancing ingredients are, however, not restricted to the aforementioned.
  • the liquid drug formulation is a suspension of fine solid particles of the compound I in a liquid.
  • the liquid can be a lipophilic or hydrophilic liquid or a mixture of several liquids. Said liquids can also comprise dissolved ingredients.
  • the surface area available for digestion and drug release is enhanced.
  • at least 90% of the drug substance shall have a particle size less than 150 micrometer, and 50% of the drug substance shall have a particle size less than 25 micrometer.
  • 90% of the drug substance shall have a particle size less than 50 micrometer, and 50% of the drug substance shall have a particle size less than 15 micrometer.
  • the liquid formulation is an emulsion.
  • the emulsion is preferably a dispersion of a lipophilic phase (e.g., a solution of compound I in a lipophilic liquid) in an aqueous phase (oil-in-water emulsion).
  • the emulsion may comprise additional components such as stabilizers (surfactants), emulsifiers and thickeners.
  • the emulsion is a microemulsion or nanoemulsion. Micro- and nanoemulsions are, in contrast to conventional emulsions, isotropic, transparent and thermodynamically stable. The average size of the dispersed droplets is in a microemulsion typically about 10000 nm or below and in a nanoemulsion 100 nm or below.
  • the liquid formulation is a syrup.
  • Typical examples of semisolid oral formulations are gels and pastes. Gels are created by adding a gelatinizer such as gelatine or a polysaccharide to a solution, suspension or emulsion comprising compound I. According to one preferred embodiment, the gel is created by addition of a gelatinizer to a microemulsion according to EP 760651 B1.
  • liquid formulations such as solutions, emulsions and suspensions can be packed in larger bottles for many doses
  • drug formulation packed into a unit dosage form, such as a capsule.
  • Such capsule formulations are called softgel capsules.
  • Soft gelatin capsules or softgel capsules consist of a liquid or semisolid matrix inside a one-piece outer shell, such as a gelatin shell.
  • the drug compound itself may be either in solution, suspension or emulsion in the capsule-fill matrix.
  • the characteristics of the fill matrix may be hydrophilic (for example polyethylene glycols) or lipophilic (such as triglyceride vegetable oils), or a mixture of both hydrophilic and lipophilic ingredients.
  • fill matrices As examples can be mentioned microemulsions or nanoemulsions of the drug encapsulated as preconcentrates in the capsule.
  • the fill matrix is a concentrated micro- or nanoemulsion, i.e., a combination of a lipophilic liquid containing the hydrophobic drug, a small amount of hydrophilic liquid and a surfactant.
  • the microemulsion After oral administration the microemulsion will become diluted in the gastrointestinal fluid.
  • the matrix may comprise only the ingredients, i.e., the drug, a lipid or a lipid mixture and one or more surfactants. The ingredients will, upon administration, spontaneously create a microemulsion (or nanoemulsion) in the gastrointestinal fluid.
  • the softgel capsule consists for example of gelatin, water and a plasticizer. It may be transparent or opaque, and can be coloured and flavoured if desired. Preservatives are not required owing to the low water activity in the finished product.
  • the softgel can be coated with enteric-resistant or delayed-release material. Although virtually any shape soft-gel can be made, oval or oblong shapes are usually selected for oral administration.
  • the improved drug formulation according to this invention is particularly useful when treating women during or after the menopause.
  • the method according to this invention is not restricted to women in this age group.
  • metabolite shall be understood to cover any ospemifene or (deaminohydroxy)toremifene metabolite already discovered or to be discovered.
  • metabolites can be mentioned the oxidation metabolites mentioned in Kangas (1990) on page 9 (TORE VI, TORE VII, TORE XVIII, TORE VIII, TORE XIII), especially TORE VI and TORE XVIII, and other metabolites of the compound.
  • the most important metabolite of ospemifene is 4-hydroxy-ospemifene, which has the formula
  • the compound (I) is preferably ospemifene.
  • the improved drug formulation according to this invention is useful in any application of ospemifene, especially when the compound is used for treatment or prevention of osteoporosis or for treatment or prevention of symptoms related to skin atrophy, or to epithelial or mucosal atrophy.
  • a particular form of atrophy which can be inhibited by administering of ospemifene is urogenital atrophy.
  • Symptoms related to urogenital atrophy can be divided in two subgroups: urinary symptoms and vaginal symptoms.
  • urinary symptoms can be mentioned micturation disorders, dysuria, hematuria, urinary frequency, sensation of urgency, urinary tract infections, urinary tract inflammation, nocturia, urinary incontinence, urge incontinence and involuntary urinary leakage.
  • vaginal symptoms can be mentioned irritation, itching, burning, malodorous discharge, infection, leukorrhea, vulvar pruritus, feeling of pressure and postcoital bleeding.
  • the optimal clinical dose of ospemifene is expected to be higher than 25 mg daily and lower than 100 mg daily.
  • a particularly preferable daily dose has been suggested in the range 30 to 90 mg.
  • ospemifene shows properties more similar to those of tamoxifen and toremifene. Due to the enhanced bioavailability according to the method of this invention, it can be predicted that the same therapeutical effect can be achieved with doses lower than those recommended earlier.
  • the solvent was a mixture of ethanol-PEG-propyleneglycol (2,7:1:2,5). The tests were separated from each other by a washout period lasting at least one week. Blood samples for the determination of serum ospemifene concentrations were collected during each test at several time points after administration. Serum ospemifene concentrations were determined using reversed phase HPLC with fluorescence detection after photochemical activation.
  • FIG. 1 discloses the mean serum concentration of ospemifene versus time after administration after a single oral dose of 60 mg ospemifene given as two 30 mg hard gelatine capsules (triangles), as one 60 mg tablet (circles) or as a dose of a solution containing 60 mg ospemifene (stars). It can be seen that peak concentrations were much higher after administration of solution (700 ng/mL) than after tablet and hard capsules, which were very similar, 280 and 277 ng/mL, respectively.
  • the AUC-values were substantially higher after solution (approximately 3000 ng h/mL) when compared to the AUC-values of tablets and hard capsules (approximately 2000 ng h/mL). Therefore it can be concluded that the absorption of ospemifene from solution was much faster and the bioavailability much higher than from tablets and hard capsules. Additionally, the variability of the pharmacokinetic parameters decreased.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Dispersion Chemistry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Oncology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Communicable Diseases (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Pregnancy & Childbirth (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US15/191,316 2004-05-04 2016-06-23 Oral formulations of ospemifene Active 2025-05-03 USRE47316E1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/191,316 USRE47316E1 (en) 2004-05-04 2016-06-23 Oral formulations of ospemifene

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US56752504P 2004-05-04 2004-05-04
PCT/FI2005/000131 WO2005105052A1 (en) 2004-05-04 2005-03-02 Novel oral formulations of ospemifene
US11/592,989 US8758821B2 (en) 2004-05-04 2006-11-06 Oral formulations of ospemifene
US15/191,316 USRE47316E1 (en) 2004-05-04 2016-06-23 Oral formulations of ospemifene

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US11/592,989 Reissue US8758821B2 (en) 2004-05-04 2006-11-06 Oral formulations of ospemifene

Publications (1)

Publication Number Publication Date
USRE47316E1 true USRE47316E1 (en) 2019-03-26

Family

ID=35241411

Family Applications (1)

Application Number Title Priority Date Filing Date
US15/191,316 Active 2025-05-03 USRE47316E1 (en) 2004-05-04 2016-06-23 Oral formulations of ospemifene

Country Status (19)

Country Link
US (1) USRE47316E1 (es)
EP (2) EP1742618B1 (es)
JP (3) JP5497983B2 (es)
KR (1) KR101278934B1 (es)
CN (1) CN1950071A (es)
AU (2) AU2005237274B2 (es)
BR (1) BRPI0510465B8 (es)
CA (1) CA2565134C (es)
CY (2) CY1113280T1 (es)
DK (2) DK2275098T3 (es)
ES (2) ES2391626T3 (es)
HK (1) HK1151227A1 (es)
MX (1) MXPA06012758A (es)
NO (2) NO338736B1 (es)
PL (2) PL1742618T3 (es)
PT (2) PT2275098E (es)
RU (1) RU2006142706A (es)
SI (2) SI2275098T1 (es)
WO (1) WO2005105052A1 (es)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101610754A (zh) * 2007-02-16 2009-12-23 Aska制药株式会社 含有微粒油性混悬液的药物组合物

Citations (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4117121A (en) 1977-04-22 1978-09-26 Hoffmann-La Roche Inc. Method of increasing bile flow and decreasing lipid levels
JPH0616556A (ja) 1992-07-02 1994-01-25 Yoshitomi Pharmaceut Ind Ltd 難溶性薬物含有製剤
JPH07165610A (ja) 1993-12-15 1995-06-27 Hiroshi Maeda 血圧制御剤
JPH07196483A (ja) 1993-11-25 1995-08-01 Taisho Pharmaceut Co Ltd 経口吸収性を改善した製剤組成物
WO1995024893A1 (en) 1994-03-16 1995-09-21 R.P. Scherer Limited Delivery systems for hydrophobic drugs
WO1996003113A1 (en) 1994-07-22 1996-02-08 G.D. Searle & Co. Self-emulsifying drug delivery system
WO1996007402A1 (en) 1994-09-07 1996-03-14 Orion-Yhtymä Oy Triphenylethylenes for the prevention and treatment of osteoporosis
US5567714A (en) 1994-10-20 1996-10-22 Eli Lilly And Company Methods of treating obesity by inhibiting physiological conditions associated with an excess of neuropeptide Y
US5597582A (en) * 1995-09-12 1997-01-28 Sanofi Oral gel capsule formulation of 1,2,4-benzotriazine oxides
WO1997032574A1 (en) 1996-03-04 1997-09-12 Orion-Yhtymä Oy Serum cholesterol lowering agent
WO1998037869A1 (fr) 1997-02-27 1998-09-03 Nippon Shinyaku Co., Ltd. Emulsion grasse s'administrant par voie orale
US6015544A (en) * 1996-03-18 2000-01-18 Map Medical Technologies Oy Process for producing radiolabelled benzodiazepine receptor agents and composition containing the same
US6245352B1 (en) 1999-04-27 2001-06-12 Eli Lilly And Company Pharmaceutical formulation
US6245819B1 (en) 2000-07-21 2001-06-12 Hormos Medical Oy, Ltd. Method for the treatment of vaginal dryness and sexual dysfunction in women during or after the menopause
EP0760651B1 (en) 1994-05-24 2001-07-04 Leiras Oy Pharmaceutical compositions derived from microelmulsion-based gels, method for their preparation and new microemulsion-based gels
WO2002056866A1 (en) 2001-01-18 2002-07-25 Orion Corporation A method for the preparation of nanoparticles
US6525084B2 (en) 1998-07-23 2003-02-25 Novo Nordisk A/S Stable pharmaceutical formulation
CA2458452A1 (en) 2001-08-10 2003-02-27 Takeda Chemical Industries, Ltd. Gnrh agonist combination drugs
US20030083228A1 (en) * 2001-08-21 2003-05-01 Carpino Philip A. Treatments for female sexual dysfunction and methods for identifying compounds useful for treating female sexual dysfunction
US20030162761A1 (en) 2000-08-24 2003-08-28 Steiner Mitchell S. Formulations comprising selective androgen receptor modulators
CN1460850A (zh) 2002-05-21 2003-12-10 株式会社百利达 电化学传感器
WO2003103649A1 (en) 2002-06-06 2003-12-18 Hormos Medical Corporation Method for the inhibition of atrophy or for treatment or prevention of atrophy-related symptoms in women
US20050182143A1 (en) 2004-02-13 2005-08-18 Hormos Medical Corporation Method for enhancing the bioavailability of ospemifene
US20050187301A1 (en) 2004-02-23 2005-08-25 Hormos Medical Corporation Solid formulations of ospemifene
US20050227947A1 (en) * 2003-04-25 2005-10-13 Chen James M Phosphonate analogs for treating metabolic diseases
US20060105045A1 (en) * 2004-11-08 2006-05-18 Buchanan Charles M Cyclodextrin solubilizers for liquid and semi-solid formulations
US20070066536A1 (en) * 2001-01-17 2007-03-22 Praecis Pharmaceuticals, Inc. Methods for treating hormone associated conditions using a combination of LHRH antagonists and specific estrogen receptor modulators

Patent Citations (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4117121A (en) 1977-04-22 1978-09-26 Hoffmann-La Roche Inc. Method of increasing bile flow and decreasing lipid levels
JPH0616556A (ja) 1992-07-02 1994-01-25 Yoshitomi Pharmaceut Ind Ltd 難溶性薬物含有製剤
JPH07196483A (ja) 1993-11-25 1995-08-01 Taisho Pharmaceut Co Ltd 経口吸収性を改善した製剤組成物
JPH07165610A (ja) 1993-12-15 1995-06-27 Hiroshi Maeda 血圧制御剤
WO1995024893A1 (en) 1994-03-16 1995-09-21 R.P. Scherer Limited Delivery systems for hydrophobic drugs
EP0760651B1 (en) 1994-05-24 2001-07-04 Leiras Oy Pharmaceutical compositions derived from microelmulsion-based gels, method for their preparation and new microemulsion-based gels
WO1996003113A1 (en) 1994-07-22 1996-02-08 G.D. Searle & Co. Self-emulsifying drug delivery system
US5912273A (en) 1994-09-07 1999-06-15 Orion-Yhtyma Oy Triphenylethylenes compositions
WO1996007402A1 (en) 1994-09-07 1996-03-14 Orion-Yhtymä Oy Triphenylethylenes for the prevention and treatment of osteoporosis
US5567714A (en) 1994-10-20 1996-10-22 Eli Lilly And Company Methods of treating obesity by inhibiting physiological conditions associated with an excess of neuropeptide Y
US5597582A (en) * 1995-09-12 1997-01-28 Sanofi Oral gel capsule formulation of 1,2,4-benzotriazine oxides
US6037379A (en) 1996-03-04 2000-03-14 Orion Corporation Serum cholesterol lowering agent
WO1997032574A1 (en) 1996-03-04 1997-09-12 Orion-Yhtymä Oy Serum cholesterol lowering agent
US6015544A (en) * 1996-03-18 2000-01-18 Map Medical Technologies Oy Process for producing radiolabelled benzodiazepine receptor agents and composition containing the same
WO1998037869A1 (fr) 1997-02-27 1998-09-03 Nippon Shinyaku Co., Ltd. Emulsion grasse s'administrant par voie orale
US6537561B1 (en) 1997-02-27 2003-03-25 Nippon Shinyaku Co., Ltd. Fat emulsion for oral administration
US6525084B2 (en) 1998-07-23 2003-02-25 Novo Nordisk A/S Stable pharmaceutical formulation
US6245352B1 (en) 1999-04-27 2001-06-12 Eli Lilly And Company Pharmaceutical formulation
JP2004504345A (ja) 2000-07-21 2004-02-12 ホルモス　メディカル　コーポレーション 閉経期または閉経後の女性における更年期障害の治療方法
WO2002007718A1 (en) 2000-07-21 2002-01-31 Hormos Medical Corporation Method for the treatment of climacteric disorders in women during or after the menopause
US20030036566A1 (en) * 2000-07-21 2003-02-20 Hormos Medical Corporation Methods for the inhibition of atrophy or for treatment or prevention of atrophy-related symptoms in women
US6984665B2 (en) 2000-07-21 2006-01-10 Hormos Medical Corporation Methods for the inhibition of atrophy or for treatment or prevention of atrophy-related symptoms in women
US6245819B1 (en) 2000-07-21 2001-06-12 Hormos Medical Oy, Ltd. Method for the treatment of vaginal dryness and sexual dysfunction in women during or after the menopause
US20030162761A1 (en) 2000-08-24 2003-08-28 Steiner Mitchell S. Formulations comprising selective androgen receptor modulators
US20070066536A1 (en) * 2001-01-17 2007-03-22 Praecis Pharmaceuticals, Inc. Methods for treating hormone associated conditions using a combination of LHRH antagonists and specific estrogen receptor modulators
WO2002056866A1 (en) 2001-01-18 2002-07-25 Orion Corporation A method for the preparation of nanoparticles
US20050215528A1 (en) 2001-08-10 2005-09-29 Shuichi Furuya Gnrh agonist combination drugs
CA2458452A1 (en) 2001-08-10 2003-02-27 Takeda Chemical Industries, Ltd. Gnrh agonist combination drugs
US20030083228A1 (en) * 2001-08-21 2003-05-01 Carpino Philip A. Treatments for female sexual dysfunction and methods for identifying compounds useful for treating female sexual dysfunction
CN1460850A (zh) 2002-05-21 2003-12-10 株式会社百利达 电化学传感器
WO2003103649A1 (en) 2002-06-06 2003-12-18 Hormos Medical Corporation Method for the inhibition of atrophy or for treatment or prevention of atrophy-related symptoms in women
US20050227947A1 (en) * 2003-04-25 2005-10-13 Chen James M Phosphonate analogs for treating metabolic diseases
US20050182143A1 (en) 2004-02-13 2005-08-18 Hormos Medical Corporation Method for enhancing the bioavailability of ospemifene
EP1713458B1 (en) 2004-02-13 2008-03-05 Hormos Medical Ltd. Method for enhancing the bioavailability of ospemifene
US20050187301A1 (en) 2004-02-23 2005-08-25 Hormos Medical Corporation Solid formulations of ospemifene
EP1718288B1 (en) 2004-02-23 2011-04-20 Hormos Medical Ltd. Solid formulations of ospemifene
US20060105045A1 (en) * 2004-11-08 2006-05-18 Buchanan Charles M Cyclodextrin solubilizers for liquid and semi-solid formulations

Non-Patent Citations (47)

* Cited by examiner, † Cited by third party
Title
Anttila, M., "Effect of food on the pharmacokinetics of toremifene," European Journal of Cancer, 33(Suppl. 8):1144 (1997).
Barth, A., et al., "Influence of Subchronic Administration of Oestradiol, Ethinyloestradiol and Oestradiol Suphamate on Bile Flow, Bile Acid Exretion, and Liver and Biliary Glutathione Status in Rats", Arch Toxicol., 71(7):443-449 (1997).
Bartha, A., et al., "Influence of Subchronic Administration of Oestradiol, Ethinyloestradiol and Oestradiol Suphamate on Bile Flow, Bile Acid Exretion, and Liver and Biliary Glutathione Status in Rats", Arch Toxicol., vol. 71, No. 7, pp. 443-449, 1997.
Basic Course in Pharmaceutical Development IX No. 15, Pharmaceutical Design Method (1), pp. 8, Chijin Shokan, Jun. 28, 1975.
Bi Dianzhou, Chinese Textbook, Pharmaceutics, Fourth Edition (2003), People's Medical Publishing House (with translation).
BI Dianzhous, English translation of Chinese Textbook cited by the examiner, Pharmaceutics, 4th ed., People's Medical Publishing House (2003).
Bolhuis, G.K., et al., "Improvement of dissolution of poorly soluble drugs by solid deposition on a super disintegrant. II. The choice of super disintegrants and effect of granulation," European Journal of Pharmaceutical Sciences, 63-69, Elsevier Science B.V. (1997).
Chinese Patent Office, Office Action for Application No. 200580004972.7 (PCT/FI2005/000037) with English translation, dated Jan. 9, 2009.
Christopher J. H. Porter, et al., "Lipid Based Formulations for Oral Administration," Journal of Receptor & Signal Transduction Research, 21 (2&3) 215-257 (2001).
Chueschov, "Industrial technology of drugs," 353-355 (1999). (with translation).
Chueschov, English translation of "Industrial technology of drugs," 353-355 (1999).
Decision of Rejection from corresponding Japanese Application No. 2012-105131, dated Jan. 10, 2012, 10 pages.
European Patent Office Examination Reports for Application No. 05 708 125.9 (PCT/FI2005/000037), dated Jul. 20, 2007.
European Patent Office Examination Reports for Application No. 05 708 125.9 (PCT/FI2005/000037), dated Mar. 25, 2008.
European Patent Office Examination Reports for Application No. 05 708 125.9 (PCT/FI2005/000037). dated Sep. 26, 2008.
European Patent Office Examination Reports for Application No. 05 717 258.7 (PCT/2005/000131), dated May 5, 2009.
European Patent Office Examination Reports for Application No. 05 717 258.7 (PCT/2005/000131), dated Nov. 9, 2007.
European Patent Office Examination Reports for Application No. 05717258.7 (PCT/FI2005/000131), dated May 5, 2009.
European Patent Office Examination Reports for Application No. 05717258.7 (PCT/FI2005/000131), dated Nov. 9, 2007.
G.K. Bolhuis, K. Zuurman, G.H.P. te Wierik; Improvement of dissolution of poorly soluble drugs by solid deposition on a super disintegant. II. The choice of super disintegrants and effect of granulation; European Journal of Pharmaceutical Sciences; 1997; 63-69; Elsevier Science B.V.
International Preliminary Report on Patentability and Written Opinion for PCT/FI2005/000037, dated May 23, 2006 (received Jun. 13, 2006).
International Preliminary Report on Patentability and Written Opinion for PCT/FI2005/000037, dated May 23, 2006.
International Preliminary Report on Patentability and Written Opinion for PCT/FI2005/000131, dated Nov. 7, 2006.
International Search Report of PCT/FI2005/000037, dated May 24, 2005.
International Search Report of PCT/FI2005/000131, dated Jun. 20, 2005.
Jordan, V. Craig, "Antiestrogens and Select Estrogen Receptor Modulators as Multifunctional Medicines, 2. Clinical Considerations and New Agents,"Journal of Medicinal Chemistry, vol. 46, No. 7, Mar. 27, 2003, pp. 1081-1111.
Jordan, V.C., "Antiestrogens and Selective Estrogen Receptor Modulators ad Multifunctional Medicines, 2. Clinical Considerations and New Agents," Journal of Medicinal Chemistry, 46(7):1081-1111 (Mar. 27, 2003).
Kangas, L., "Biochemical and pharmacological effects of toremifene metabolites," Cancer Chemotherapy and Pharmacology, 27:8-12 (1990).
Karlsson, M. O., et al., "Pharmacokinetics of Oral Noscapine", Eur J Clin Pharmacol., 39(3):275-279 (1990).
Kauffman, RF, et al., "Selective Estrogen Receptor Modulators," Drug News Perspect, 8:531-539 (1995).
Laight, S.J., et al., "Comparative evaluation of two aspirin formulation techniques," www.ru.ac.za/academic/departments/pharmacy/jrats/vol1_1/poster5/tablet2.html, printed Dec. 3, 2017; 1-6.
New Theories of Pharmacology: Third Edition, pp. 19, Nankodo Press, Apr. 10, 1987.
Odeku, Oluwatoyin A., et al., "Effects of the method of preparation on the compression, mechanical, and release properties of Khaya gum matrices," Pharmaceutical Development and Technology, 11(4):435-441 (2006).
Office Action with English translation for Chinese Application No. 200580004972.7 (PCT/FI2005/000037), dated Jan. 9, 2009.
Office Action with English translation for Russian Application No. 2006133902, dated Dec. 14, 2009.
Office Action with English translation for Russian Application No. 2006133902, dated Jan. 26, 2009.
Patent Office of the Russian Federation, Official Action for Application No. 2006133902 with English translation, dated Dec. 14, 2009.
Patent Office of the Russian Federation, Official Action for Application No. 2006133902 with English translation, dated Jan. 26, 2009.
Porter, Christopher J. H., et al., "Lipid Based Formulations for Oral Administration," J. of Receptor & Signal Transduction Research, 21(2&3):215-257 (2001).
Quinton Singh, Hiren Patel, Mohamed Cassim; Comparative Evaluations of Tablet Formulations; Rhodes University, School of Pharmaceutical Sciences, Department of Pharmaceutics, Rhodes University, Grahamstown, 6140, RSA; www.ru.ac.za/academic/departments/pharmacy/jrats/vol1_1/poster6/tablet8.html; printed Dec. 3, 2007; 1-6.
Raymond F. Kauffman, et al., "Selective Estrogen Receptor Modulators," Drug News & Perspectives 1995 8 (9) pp. 531-539.
Rudnic, E.M., "Oral Solid Dosage Forms", Remington: The Science and Practice of Pharmacy, Gennaro, A.R., editor, 20th Ed. Chapter 45, pp. 858-871, dated Dec. 15, 2000.
Rudnic, E.M., "Oral Solid Dosage Forms," Remington: The Science and Practice of Pharmacy, Gennaro, A.R., editor, 20th Ed. Chapter 45, pp. 858-871.
Seki, T., "Basics of Pharmaceutical Treatment", Clinical Nutrition, 101(1):26-31 (Jul. 2002).
Singh, Quinton, et al., "Comparative Evaluations of Tablet Formulations," Rhodes University, School of Pharmaceutical Sciences, Department of Pharmaceutics, Rhodes University, Grahamstown, 6140, RSA, www.ru.ac.za/academic/departments/pharmacy/jrats/vol1_1/poster6/tablets8.html, printed Dec. 3, 2017; 1-6.
Skinner, M. And Kanfer, I., "Comparative Bioavailability of Josamycin, a Macrolide Antibiotic, from a Tablet and Solution and the Influence of Dissolution on in Vivo Release", Biopharm Drug Dispos., 19(1):21-29 (Jan. 1998).
Voipio, S.K., et al. "Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women," Maturitas, 43:207-214 (2002).

Also Published As

Publication number Publication date
WO2005105052A1 (en) 2005-11-10
PT2275098E (pt) 2012-08-29
AU2005237274B2 (en) 2011-02-17
JP2014156495A (ja) 2014-08-28
AU2011202264B2 (en) 2012-03-15
PL1742618T3 (pl) 2013-01-31
AU2005237274A1 (en) 2005-11-10
EP1742618B1 (en) 2012-08-22
MXPA06012758A (es) 2007-01-16
JP2012149094A (ja) 2012-08-09
DK2275098T3 (da) 2012-08-20
AU2011202264A1 (en) 2011-06-09
NO20065074L (no) 2006-11-29
CA2565134A1 (en) 2005-11-10
KR20070005715A (ko) 2007-01-10
CA2565134C (en) 2013-05-21
RU2006142706A (ru) 2008-06-20
SI1742618T1 (sl) 2012-12-31
EP1742618A1 (en) 2007-01-17
NO343582B1 (no) 2019-04-08
NO20161206A1 (no) 2006-11-29
DK1742618T3 (da) 2012-10-01
BRPI0510465B8 (pt) 2021-05-25
BRPI0510465A (pt) 2007-11-06
AU2011202264A8 (en) 2012-04-05
EP2275098A1 (en) 2011-01-19
JP5834111B2 (ja) 2015-12-16
PT1742618E (pt) 2012-10-11
PL2275098T3 (pl) 2012-12-31
BRPI0510465B1 (pt) 2019-08-27
ES2392344T3 (es) 2012-12-07
AU2011202264B8 (en) 2012-04-05
CY1113280T1 (el) 2016-04-13
KR101278934B1 (ko) 2013-06-26
CY1113284T1 (el) 2016-04-13
NO338736B1 (no) 2016-10-17
HK1151227A1 (en) 2012-01-27
CN1950071A (zh) 2007-04-18
JP5497983B2 (ja) 2014-05-21
JP2007536351A (ja) 2007-12-13
SI2275098T1 (sl) 2012-12-31
EP2275098B1 (en) 2012-07-25
ES2391626T3 (es) 2012-11-28
JP5643255B2 (ja) 2014-12-17

Similar Documents

Publication Publication Date Title
US8758821B2 (en) Oral formulations of ospemifene
EP0955042B1 (fr) Composition pharmaceutique à base d'estrogène et de progestérone
US9241915B2 (en) Method for enhancing the bioavailability of ospemifene
US20070104743A1 (en) Formulations of fispemifene
USRE47316E1 (en) Oral formulations of ospemifene
MX2008006171A (es) Formulaciones de fispemifeno

Legal Events

Date Code Title Description
AS Assignment

Owner name: DUCHESNAY INC., CANADA

Free format text: MOVABLE HYPOTHEC;ASSIGNOR:SHIONOGI INC.;REEL/FRAME:042233/0807

Effective date: 20170310

AS Assignment

Owner name: QUATRX PHARMACEUTICALS COMPANY, MICHIGAN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:HORMOS MEDICAL OY;REEL/FRAME:046240/0156

Effective date: 20180328

MAFP Maintenance fee payment

Free format text: PAYMENT OF MAINTENANCE FEE, 8TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: M1552); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

Year of fee payment: 8