US20030125387A1 - Fulvestrant formulation - Google Patents

Fulvestrant formulation Download PDF

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US20030125387A1
US20030125387A1 US10/169,777 US16977702A US2003125387A1 US 20030125387 A1 US20030125387 A1 US 20030125387A1 US 16977702 A US16977702 A US 16977702A US 2003125387 A1 US2003125387 A1 US 2003125387A1
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formulation
pharmaceutically
fulvestrant
pharmaceutical formulation
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John Evans
Rosalind Grundy
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AstraZeneca AB
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AstraZeneca AB
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    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/32—Antioestrogens
    • 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
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • the invention relates to a novel sustained release pharmaceutical formulation adapted for administration by injection containing the compound 7 ⁇ -[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-triene-3,17 ⁇ -diol, more particularly to a formulation adapted for administration by injection containing the compound 7 ⁇ -[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-triene-3,17 ⁇ -diol in solution in a ricinoleate vehicle which additionally comprises at least one alcohol and a non-aqueous ester solvent which is miscible in the ricinoleate vehicle.
  • Oestrogen deprivation is fundamental to the treatment of many benign and malignant diseases of the breast and reproductive tract. In premenopausal women, this is achieved by the ablation of ovarian function through surgical, radiotherapeutic, or medical means, and, in postmenopausal women, by the use of aromatase inhibitors.
  • oestrogen withdrawal is to antagonise oestrogens with antioestrogens.
  • drugs that bind to and compete for oestrogen receptors (ER) present in the nuclei of oestrogen-responsive tissue.
  • ER oestrogen receptors
  • Conventional nonsteroidal antioestrogens, such as tamoxifen compete efficiently for ER binding but their effectiveness is often limited by the partial agonism they display, which results in an incomplete blockade of oestrogen-mediated activity (Furr and Jordan 1984, May and Westley 1987).
  • Steroidal analogues of oestradiol with an alkylsulphinyl side chain in the 7 ⁇ position, provided the first examples of compounds devoid of oestrogenic activity (Bowler et al 1989).
  • 7 ⁇ -[9-(4,4,5,5,5-pentafluoropentyl sulphinyl)nonyl]oestra- 1,3,5-(10)triene-3,17 ⁇ -diol was selected for intensive study on the basis of its pure oestrogen antagonist activity and significantly increased antioestrogenic potency over other available antioestrogens.
  • Fulvestrant binds to ER with an affinity similar to that of oestradiol and completely blocks the growth stimulatory action of oestradiol on human breast cancer cells in vitro; it is more potent and more effective than tamoxifen in this respect. Fulvestrant blocks completely the uterotrophic action of oestradiol in rats, mice and monkeys, and also blocks the uterotrophic activity of tamoxifen.
  • fulvestrant Because fulvestrant has none of the oestrogen-like stimulatory activity that is characteristic of clinically available antioestrogens such as tamoxifen or toremifene, it may offer improved therapeutic activity characterised by more rapid, complete, or longer-lasting tumour regression; a lower incidence or rate of development of resistance to treatment; and a reduction of tumour invasiveness.
  • fulvestrant In intact adult rats, fulvestrant achieves maximum regression of the uterus at a dose which does not adversely affect bone density or lead to increased gonadotrophin secretion. If also true in humans, these findings could be of extreme importance clinically. Reduced bone density limits the duration of oestrogen-ablative treatment for endometriosis. Fulvestrant does not block hypothalamic ER. Oestrogen ablation also causes or exacerbates hot flushes and other menopausal symptoms; fulvestrant will not cause such effects because it does not cross the blood-brain barrier.
  • European Patent Application No. 0 138 504 discloses that certain steroid derivatives are effective antioestrogenic agents.
  • the disclosure includes information relating to the preparation of the steroid derivatives.
  • Example 35 the compound 7 ⁇ -[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-triene-3,17, ⁇ -diol, which compound is specifically named in claim 4.
  • the compounds of that invention may be provided for use in the form of a pharmaceutical composition comprising a steroid derivative of the invention together with a pharmaceutically-acceptable diluent or carrier. It is stated therein that the composition can be in a form suitable for oral or parenteral administration.
  • Fulvestrant shows, along with other steroidal based compounds, certain physical properties which make formulation of these compounds difficult. Fulvestrant is a particularly lipophilic molecule, even when compared with other steroidal compounds, and its aqueous solubility is extremely low at around 10 ngml ⁇ 1 (this is an estimate from a water/solvent mixture solute since measurements this low could not be achieved in a water only solute).
  • Vidal Castor YES 1 or 1 week RETARD caproate mgml ⁇ 1 1999 2 ml GRAVIBINAN Estradiol 17- ⁇ -valerate 5 Mixed Schering Dict.
  • Table 2 shows the solubility of fulvestrant in a number of different solvents.
  • SOLUBILITY OF FULVESTRANT SOLUBILITY SOLVENT (mgml ⁇ 1 at 25° C.) Water 0.001 Arachis oil 0.45 Sesame oil 0.58 Castor oil 20 Miglyol 810 3.06 Miglyol 812 2.72 Ethyl oleate 1.25 Benzyl benzoate 6.15 Isopropyl myristate 0.80 Span 85 (surfactant) 3.79 Ethanol >200 Benzyl Alcohol >200
  • fulvestrant is significantly more soluble in castor oil than any of the other oils tested.
  • the greater solvating ability of castor oil for steroidal compounds is known and is attributed to the high number of hydroxy groups of ricinoleic acid, which is the major constituent of the fatty acids within the triglycerides present in castor oil—see (Riffkin et.al. J. Pharm. Sci., (1964), 53, 891).
  • a pharmaceutical formulation comprising fulvestrant (preferably fulvestrant is present at 3-10% w/v, 4-9% w/v, 4-8% w/v, 4-7% w/v, 4-6% w/v and most preferably at about 5% w/v) in a ricinoleate vehicle, a pharmaceutically acceptable non-aqueous ester solvent, and a pharmaceutically acceptable alcohol wherein the formulation is adapted for intramuscular administration and attaining a therapeutically significant blood plasma fulvestrant concentration for at least 2 weeks.
  • fulvestrant preferably fulvestrant is present at 3-10% w/v, 4-9% w/v, 4-8% w/v, 4-7% w/v, 4-6% w/v and most preferably at about 5% w/v
  • Another feature of the invention is a pharmaceutical formulation comprising fulvestrant in which the formulation is adapted for intra-muscular injection into a human and which is capable after injection of attaining a therapeutically significant blood plasma fulvestrant concentration for at least 2 weeks.
  • compositions adapted for intra-muscular injection comprising fulvestrant, 30% or less weight of a pharmaceutically-acceptable alcohol per volume of formulation, at least 1% weight of a pharmaceutically-acceptable non-aqueous ester solvent miscible in a ricinoleate vehicle per volume of formulation and a sufficient amount of a ricinoleate vehicle so as to prepare a formulation which is capable after injection of attaining a therapeutically significant blood plasma fulvestrant concentration for at least 2 weeks.
  • compositions adapted for intra-muscular injection comprising fulvestrant; 35% (preferably 30% and ideally 25%) or less weight of a pharmaceutically-acceptable alcohol per volume of formulation, at least 1% (preferably at least 5% or ideally 10%) weight of a pharmaceutically-acceptable non-aqueous ester solvent miscible within a ricinoleate vehicle per volume of formulation and a sufficient amount of a ricinoleate vehicle so as to prepare a formulation of at least 45 mgml ⁇ 1 of fulvestrant.
  • % weight per volume of formulation for the constituents of the formulation we mean that within a unit volume of the formulation a certain percentage of the constituent by weight will be present, for example a 1% weight per volume formulation will contain within a 100 ml volume of formulation 1 g of the constituent.
  • the total volume of the formulation is 6 ml, or less, and the concentration of fulvestrant is at least 45 mgml ⁇ 1 .
  • the total amount of fulvestrant in the formulation is 250 mg, or more, and the total volume of the formulation is 6 ml, or less.
  • the total amount of fulvestrant in the formulation is 250 mg and the total volume of the formulation is 5-5.25 ml.
  • Preferred concentrations of a pharmaceutically-acceptable alcohol present in any of the above formulations are; at least 3% w/v, at least 5% w/v, at least 7% w/v, at least 10% w/v, at least 11% w/v, at least 12% w/v, at least 13% w/v, at least 14% w/v, at least 15% w/v and, preferably, at least 16% w/v.
  • Preferred maximal concentrations of pharmaceutically-acceptable alcohol present in the formulation are; 28% w/v or less, 22% w/v or less and 20% w/v or less.
  • Preferred ranges of pharmaceutically-acceptable alcohol present in any of the above formulations are selected from any minimum or maximum value described above and preferably are; 3-35% w/v, 4-35% w/v, 5-35% w/v, 5-32% w/v, 7-32% w/v, 10-30% w/v, 12-28% w/v, 15-25% w/v, 17-23% w/v, 18-22% w/v and ideally 19-21% w/v.
  • the pharmaceutically-acceptable alcohol may consist of one alcohol or a mixture of two or more alcohols, preferably a mixture of two alcohols.
  • Preferred pharmaceutically-acceptable alcohols for parenteral administration are ethanol, benzyl alcohol or a mixture of both ethanol and benzyl alcohol, preferably the ethanol and benzyl alcohol are present in the formulation in the same w/v amounts.
  • the formulation alcohol contains 10% w/v ethanol and 10% w/v benzyl alcohol.
  • the pharmaceutically-acceptable non-aqueous ester solvent may consist of one or a mixture of two or more pharmaceutically-acceptable non-aqueous ester solvents, preferably just one.
  • a preferred pharmaceutically-acceptable non-aqueous ester solvent for parenteral administration is selected from benzyl benzoate, ethyl oleate, isopropyl myristate, isopropyl palmitate or a mixture of any thereof.
  • the ricinoleate vehicle should preferably be present in the formulation in a proportion of at least 30% weight per volume of the formulation, ideally at least 40% or at least 50% weight per volume of formulation.
  • the pharmaceutically-acceptable alcohol will be of a quality such that it will meet pharmacopoeial standards (such as are described in the U.S., British, European and Japanese pharmacopoeias) and as such will contain some water and possibly other organic solvents, for example ethanol in the U.S. Pharmacopeia contains not less than 94.9% by volume and not more than 96.0% by volume of ethanol when measured at 15.56° C. Dehydrated alcohol in the U.S. Pharmacopeia contains not less than 99.5% ethanol by volume when measured at 15.56° C.
  • Preferred concentrations of the pharmaceutically-acceptable non-aqueous ester solvent present in any of the above formulations are; at least 5% w/v, at least 8% w/v, at least 10% w/v, at least 11% w/v, at least 12% w/v, at least 13% w/v, at least 15% w/v, at least 16% w/v, at least 17% w/v, at least 18% w/v, at least 19% w/v and at least 20% w/v.
  • Preferred maximal concentrations of the pharmaceutically-acceptable non-aqueous ester solvent are; 60% w/v or less, 50% w/v or less, 45% w/v or less, 40% w/v or less, 35% w/v or less, 30% w/v or less and 25% w/v or less.
  • a preferred concentration is 15% w/v.
  • Preferred ranges of pharmaceutically-acceptable non-aqueous ester solvent present in any of the above formulations are selected from any minimum or maximum value described above and preferably are; 5-60% w/v, 7-55% w/v, 8-50% w/v, 10-50% w/v, 10-45% w/v, 10-40% w/v, 10-35% w/v, 10-30% w/v, 10-25% w/v, 12-25% w/v, 12-22% w/v, 12-20% w/v, 12-18% w/v, 13-17% w/v and ideally 14-16% w/v.
  • the ester solvent is benzyl benzoate, most preferably at about 15% w/v.
  • the pharmaceutically-acceptable non-aqueous ester solvent will be of a quality that it will meet pharmacopoeial standards (such as described in the U.S., British, European and Japanese pharmacopoeias).
  • Preferred combinations of pharmaceutically-acceptable alcohol and pharmaceutically-acceptable non-aqueous ester solvent in the formulation are set out below:
  • ricinoleate vehicle we mean an oil which has as a proportion (at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% w/v) of its composition as triglycerides of ricinoleic acid.
  • the ricinoleate vehicle may be a synthetic oil or conveniently is castor oil, ideally of pharmacopoeial standards, as described above.
  • terapéuticaally significant levels we mean that blood plasma concentrations of at least 2.5 ngml ⁇ 1 , ideally at least 3 ngml ⁇ 1 , at least 8.5 ngml ⁇ 1 , and up to 12 ngml ⁇ 1 of fulvestrant are achieved in the patient. Preferably blood plasma levels should be less than 15 ngml ⁇ 1 .
  • extended release we mean at least two weeks, at least three weeks, and, preferably at least four weeks of continuous release of fulvestrant is achieved. In a preferred feature extended release is achieved for 36 days. Preferably extended release of fulvestrant is for at least 2-5 weeks and more preferably for the following periods (weeks) 2.5-5, 2.5-4, 3-4, 3.5-4 and most preferably for at least about 4 weeks.
  • Table 3 shows the solubility of fulvestrant in a castor oil vehicle additionally containing alcohols ethanol and benzyl alcohol with or without benzyl benzoate. The results clearly show the positive effect of benzyl benzoate on fulvestrant solubility in castor oil, despite fulvestrant having a lower solubility in benzyl benzoate than in either alcohol or castor oil.
  • Vehicle minus Formulation (a) Complete vehicle alcohols Castor oil based 81.2 12.6 Miglyol 812-N based 86.8 1.7 Sesame seed/Castor oil (1:1) based 70.1 4.4 Sesame seed oil based 45.7 0.7 Arachis oil based 40.2 ⁇ 0.2 Effect of formulation on precipitation of fulvestranqt at the injection site Days Formulation a 2 3 4 7 10 30 51 Formulation F1 0 0 0 0 0 0 0 castor oil based Formulation F2 ++ b +++ +++ +++ +++ ++ 0 Miglyol 812-N based Formulation F3 + c ++ ++ +++ ++ + + sesame seed oil/castor oil based
  • the castor oil formulation showed a particularly even release profile with no evidence of precipitation of fulvestrant at the injection site.
  • an extended release pharmaceutical formulation adapted for intramuscular injection comprising fulvestrant; 35% (preferably 30% or ideally 25%) or less weight of a pharmaceutically-acceptable alcohol per volume of formulation, at least 1% (preferably at least 5% or ideally 10%) weight of a pharmaceutically-acceptable non-aqueous ester solvent miscible in a ricinoleate vehicle per volume of formulation and sufficient amount of a ricinoleate vehicle, taking into account the addition of any further optional pharmaceutically-acceptable excipients, so as to prepare a formulation of at least 45 mgml ⁇ 1 of fulvestrant.
  • a further feature of the invention is a pharmaceutical formulation adapted for intramuscular injection, as defined above, for use in medical therapy.
  • a further feature of the invention is a method of treating a benign or malignant diseases of the breast or reproductive tract, preferably treating breast cancer, by administration to a human in need of such treatment by intramuscular injection an extended release ricinoleate vehicle based pharmaceutical formulation comprising at least 45 mgml ⁇ 1 of fulvestrant; 35% (preferably 30% or ideally 25%) or less weight of a pharmaceutically-acceptable alcohol per volume of formulation, at least 1% (preferably at least 5% or ideally 10%) weight of a pharmaceutically-acceptable non-aqueous ester solvent miscible in a ricinoleate vehicle per volume of formulation.
  • a further feature of the invention is use of fulvestrant in the preparation of a pharmaceutical formulation as describe hereinabove, for the treatment of a benign or malignant disease of the breast or reproductive tract, preferably treating breast cancer.
  • excipients commonly used in the formulation field including, for example, an antioxidant preservative, a colorant or a surfactant may be used.
  • a preferred optional excipient is a surfactant.
  • fulvestrant is useful in the treatment of oestrogen-dependent indications such as breast cancer and gynaecological conditions, such as endometriosis.
  • SH-646 11 ⁇ -fluoro-7 ⁇ -(14,14,15,15,15-pentafluoro-6-methyl-10-thia-6-azapentadecyl)estra-1,3,5(10)-triene-3,17 ⁇ -diol
  • SH-646 11 ⁇ -fluoro-7 ⁇ -(14,14,15,15,15-pentafluoro-6-methyl-10-thia-6-azapentadecyl)estra-1,3,5(10)-triene-3,17 ⁇ -diol
  • a further feature of the invention is a pharmaceutical formulation adapted for intra-muscular injection comprising 11 ⁇ -fluoro-7 ⁇ -(14,14,15,15,15-pentafluoro-6-methyl-10-thia-6-azapentadecyl)estra-1,3,5(10)-triene-3,17 ⁇ -diol; 35% or less weight of a pharmaceutically-acceptable alcohol per volume of formulation, at least 1% weight of a pharmaceutically-acceptable non-aqueous ester solvent miscible within a ricinoleate vehicle per volume of formulation and a sufficient amount of a ricinoleate vehicle so as to prepare a formulation of at least 45 mgml ⁇ 1 of 11 ⁇ -fluoro-7 ⁇ -(14,14,15,15,15-pentafluoro-6-methyl-10-thia-6-azapentadecyl)estra-1,3,5(10)-triene-3,17 ⁇ -diol.
  • Fulvestrant is mixed with alcohol and benzyl alcohol, stirring until completely dissolved. Benzyl benzoate is added and the solution is made to final weight with castor oil and stirred, (for convenience weight is used rather than volume by using the weight to volume ratio).
  • the bulk solution is overlaid with Nitrogen.
  • the solution is sterilised by filtration using one or two filters of 0.2 ⁇ m porosity.
  • the sterile filtrate is kept under a nitrogen overlay as it is filled under aseptic conditions into washed and depyrogenised, sterile primary containers, for example vials or pre-filled syringes. An overage is included in the primary pack to facilitate removal of the dose volume.
  • the primary packs are overlaid with sterile nitrogen, before aseptically sealing.
US10/169,777 2000-01-10 2001-01-08 Fulvestrant formulation Abandoned US20030125387A1 (en)

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Application Number Priority Date Filing Date Title
GBGB0000313.7A GB0000313D0 (en) 2000-01-10 2000-01-10 Formulation
GB0000313.7 2000-01-10
GBGB0008837.7A GB0008837D0 (en) 2000-01-10 2000-04-12 Formulation
GB0008837.7 2000-04-12

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US10/169,777 Abandoned US20030125387A1 (en) 2000-01-10 2001-01-08 Fulvestrant formulation
US09/756,291 Expired - Lifetime US6774122B2 (en) 2000-01-10 2001-01-09 Formulation
US10/872,784 Expired - Lifetime US7456160B2 (en) 2000-01-10 2004-06-22 Formulation
US12/285,887 Active 2025-05-26 US8329680B2 (en) 2000-01-10 2008-10-15 Formulation
US13/602,667 Expired - Lifetime US8466139B2 (en) 2000-01-10 2012-09-04 Formulation

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US09/756,291 Expired - Lifetime US6774122B2 (en) 2000-01-10 2001-01-09 Formulation
US10/872,784 Expired - Lifetime US7456160B2 (en) 2000-01-10 2004-06-22 Formulation
US12/285,887 Active 2025-05-26 US8329680B2 (en) 2000-01-10 2008-10-15 Formulation
US13/602,667 Expired - Lifetime US8466139B2 (en) 2000-01-10 2012-09-04 Formulation

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Cited By (1)

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US9271990B2 (en) 2014-02-14 2016-03-01 Fresenius Kabi Usa, Llc Fulvestrant formulations

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GB0000313D0 (en) * 2000-01-10 2000-03-01 Astrazeneca Uk Ltd Formulation
GB0116620D0 (en) * 2001-07-07 2001-08-29 Astrazeneca Ab Formulation
CN1553815A (zh) * 2001-07-07 2004-12-08 用于肌内给药的氟维司群药物制剂
NZ571508A (en) * 2002-05-24 2010-05-28 Schering Corp Neutralizing human anti-IGFR antibody
TW200404552A (en) * 2002-05-30 2004-04-01 Akzo Nobel Nv Self administered contraception
US20050152858A1 (en) * 2003-07-11 2005-07-14 Isp Investments Inc. Solubilizing agents for active or functional organic compounds
TW200526684A (en) * 2003-11-21 2005-08-16 Schering Corp Anti-IGFR1 antibody therapeutic combinations
EP1623713A1 (en) * 2004-07-09 2006-02-08 Proskelia SAS Cominations of pure anti-estrogen with aromatase inhibitors
MX2007012896A (es) * 2005-04-15 2007-12-10 Schering Corp Metodos y composiciones para tratamiento o prevencion de cancer.
WO2007033434A1 (en) * 2005-09-26 2007-03-29 Hospira Australia Pty Ltd Fulvestrant formulation
KR20100121505A (ko) * 2008-03-07 2010-11-17 싸이도우스 엘엘씨. 플배스트랜 제제
GB0807605D0 (en) * 2008-04-28 2008-06-04 Diurnal Ltd Lipid composition
AU2014200332B2 (en) * 2008-04-28 2016-10-06 Diurnal Limited Lipid composition
UA104147C2 (uk) * 2008-09-10 2014-01-10 Новартис Аг Похідна піролідиндикарбонової кислоти та її застосування у лікуванні проліферативних захворювань
US20100317635A1 (en) 2009-06-16 2010-12-16 Endorecherche, Inc. Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators
CN102939287B (zh) 2010-06-10 2016-01-27 塞拉根制药公司 雌激素受体调节剂及其用途
US8853423B2 (en) 2010-06-17 2014-10-07 Seragon Pharmaceuticals, Inc. Indane estrogen receptor modulators and uses thereof
EP2616078B1 (en) 2010-09-16 2019-12-25 Shimoda Biotech (Pty) Ltd Fulvestrant compositions and methods of use
US9029582B2 (en) 2011-05-20 2015-05-12 Capital, Business Y Gestion De Finanzas S.L. Pharmaceutical composition
CN102391341B (zh) * 2011-08-09 2013-05-22 福建省微生物研究所 制备6,7-脱氢-17β-烃酰氧基诺龙的方法
CN103070871B (zh) * 2011-10-26 2015-04-15 正大天晴药业集团股份有限公司 一种氟维司群的药物组合物
ES2885523T3 (es) 2011-11-23 2021-12-14 Therapeuticsmd Inc Formulaciones y terapias de reposición hormonal de combinación naturales
US9301920B2 (en) 2012-06-18 2016-04-05 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US9193714B2 (en) 2011-12-14 2015-11-24 Seragon Pharmaceuticals, Inc. Fluorinated estrogen receptor modulators and uses thereof
MD20140054A2 (ro) 2011-12-16 2014-10-31 Olema Pharmaceuticals, Inc. Compuşi noi de benzopiran, compoziţii şi utilizări ale acestora
CN102600073B (zh) 2012-03-31 2014-01-01 莱普德制药有限公司 以乳酸酯为基础的氟维司群或其衍生物油性制剂及其制备方法
CN102600064A (zh) * 2012-03-31 2012-07-25 西安力邦制药有限公司 氟维司群或其衍生物缓释制剂及其制备方法
US11179468B2 (en) 2012-04-09 2021-11-23 Eagle Pharmaceuticals, Inc. Fulvestrant formulations
EP2836199A1 (en) * 2012-04-09 2015-02-18 Scidose LLC Fulvestrant formulations
US20150196640A1 (en) 2012-06-18 2015-07-16 Therapeuticsmd, Inc. Progesterone formulations having a desirable pk profile
US10806740B2 (en) 2012-06-18 2020-10-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US20130338122A1 (en) 2012-06-18 2013-12-19 Therapeuticsmd, Inc. Transdermal hormone replacement therapies
US10806697B2 (en) 2012-12-21 2020-10-20 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10568891B2 (en) 2012-12-21 2020-02-25 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11266661B2 (en) 2012-12-21 2022-03-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10537581B2 (en) 2012-12-21 2020-01-21 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US9180091B2 (en) 2012-12-21 2015-11-10 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
EP2987799B1 (en) 2013-04-18 2020-04-08 Xi'an Libang Pharmaceutical Technology Co.,ltd. Ester derivative of 7-alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-triene-3,17beta-diol having antitumour activity and preparation method thereof
US10392667B2 (en) 2013-06-07 2019-08-27 Medical Prognosis Institute A/S Methods and devices for predicting treatment efficacy of fulvestrant in cancer patients
WO2014203132A1 (en) 2013-06-19 2014-12-24 Olema Pharmaceuticals, Inc. Substituted benzopyran compounds, compositions and uses thereof
WO2014203129A1 (en) 2013-06-19 2014-12-24 Olema Pharmaceuticals, Inc. Combinations of benzopyran compounds, compositions and uses thereof
CN104337761B (zh) * 2013-08-07 2019-03-26 江苏豪森药业集团有限公司 氟维司群药物组合物
WO2015033302A2 (en) * 2013-09-06 2015-03-12 Salah Uddin Ahmed Fulvestrant compositions
WO2015136016A2 (en) 2014-03-13 2015-09-17 F. Hoffmann-La Roche Ag Therapeutic combinations with estrogen receptor modulators
AU2015264003A1 (en) 2014-05-22 2016-11-17 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
WO2016018993A1 (en) 2014-07-29 2016-02-04 Therapeuticsmd, Inc. Transdermal cream
KR20230113416A (ko) 2014-12-18 2023-07-28 에프. 호프만-라 로슈 아게 테트라하이드로-피리도[3,4-b]인돌 에스트로겐 수용체조절제 및 이의 용도
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
KR20180071274A (ko) 2015-10-01 2018-06-27 올레마 파마슈티컬스 인코포레이티드 테트라히드로-1H-피리도[3,4-b]인돌 항에스트로겐 약물
BR112018007486A2 (pt) 2015-10-13 2018-10-23 Nevakar Llc composição de fulvestrant pronta para injetar e método para a fabricação de um artigo contendo uma composição de fulvestrant pronta para injetar
MX2018007079A (es) 2015-12-09 2018-11-12 The Board Of Trustees Of Univ Of Illinois Reguladores a la baja del receptor de estrogeno selectivo de benzotiofeno.
WO2017173071A1 (en) 2016-04-01 2017-10-05 Therapeuticsmd, Inc. Steroid hormone pharmaceutical composition
US10286077B2 (en) 2016-04-01 2019-05-14 Therapeuticsmd, Inc. Steroid hormone compositions in medium chain oils
CN108883118B (zh) 2016-04-06 2021-06-15 富士胶片株式会社 医药组合物
EP3440067B1 (en) 2016-04-08 2021-05-26 F. Hoffmann-La Roche AG Tetrahydroisoquinoline estrogen receptor modulators and uses thereof
US11590077B2 (en) 2016-05-06 2023-02-28 Eagle Pharmaceuticals, Inc. Fulvestrant formulations and methods of their use
BR112018072768A2 (pt) * 2016-05-06 2019-02-19 Eagle Pharmaceuticals, Inc. suspensão, composição farmacêutica, método para formar uma suspensão fulvestrant aquosa, suspensão fulvestrant aquosa e método para tratar um indivíduo tendo câncer de mama
WO2019094650A1 (en) * 2017-11-08 2019-05-16 Eagle Pharmaceuticals, Inc Fulvestrant formulations and methods of their use
WO2017208847A1 (ja) * 2016-05-31 2017-12-07 富士フイルム株式会社 医薬組成物
CN109843882A (zh) 2016-06-16 2019-06-04 豪夫迈·罗氏有限公司 四氢-吡啶并[3,4-b]吲哚雌激素受体调节剂及其用途
US20180002344A1 (en) 2016-06-16 2018-01-04 Genentech, Inc. Heteroaryl estrogen receptor modulators and uses thereof
JP7018026B2 (ja) * 2016-06-16 2022-02-09 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト ヘテロアリールエストロゲン受容体モジュレーター及びその使用
CN107789320B (zh) * 2016-08-31 2021-06-22 鲁南制药集团股份有限公司 一种氟维司群缓释注射液及其制备工艺
AU2018329202B2 (en) 2017-09-11 2022-10-27 Atossa Therapeutics, Inc. Methods for making and using endoxifen
CA3081602A1 (en) 2017-11-16 2019-05-23 Novartis Ag Combination therapies
WO2019151353A1 (ja) * 2018-01-31 2019-08-08 富士フイルム株式会社 注射用製剤の製造方法
RU2684330C1 (ru) * 2018-02-02 2019-04-08 Закрытое Акционерное Общество "Биокад" Композиции фулвестранта
AU2019274815A1 (en) 2018-05-24 2021-01-21 Shivanka Research LLC Prodrugs of fulvestrant
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
CN111035613A (zh) * 2018-10-12 2020-04-21 江苏恒瑞医药股份有限公司 一种包含氟维司群的可注射的药物组合物及其制备方法
AU2019374142A1 (en) 2018-11-01 2021-05-27 Syros Pharmaceuticals, Inc. Methods of treating cancer in biomarker-identified patients with non-covalent inhibitors of cyclin-dependent kinase 7 (CDK7)
JP2022514315A (ja) 2018-12-20 2022-02-10 ノバルティス アーゲー ３－（１－オキソイソインドリン－２－イル）ピペリジン－２，６－ジオン誘導体を含む投与計画及び薬剤組み合わせ
KR20210129672A (ko) 2019-02-15 2021-10-28 노파르티스 아게 치환된 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체 및 이의 용도
CA3124935A1 (en) 2019-02-15 2020-08-20 Novartis Ag 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2020236825A2 (en) 2019-05-20 2020-11-26 Novartis Ag Mcl-1 inhibitor antibody-drug conjugates and methods of use
RU2722988C1 (ru) * 2019-11-19 2020-06-05 федеральное государственное бюджетное образовательное учреждение высшего образования "Башкирский государственный медицинский университет" Министерства здравоохранения Российской Федерации Способ моделирования проканцерогенного действия фулвестранта на яичники потомства женского пола у лабораторных мышей
JP2023504867A (ja) * 2019-12-11 2023-02-07 上海博志研新薬物技術有限公司 フルベストラント医薬組成物、その調製方法及び応用
CN115052662A (zh) 2019-12-20 2022-09-13 诺华股份有限公司 抗TGFβ抗体和检查点抑制剂用于治疗增殖性疾病的用途
US11633405B2 (en) 2020-02-07 2023-04-25 Therapeuticsmd, Inc. Steroid hormone pharmaceutical formulations
JP2023531676A (ja) 2020-06-23 2023-07-25 ノバルティス アーゲー ３－（１－オキソイソインドリン－２－イル）ピぺリジン－２，６－ジオン誘導体を含む投与レジメン
CN116134027A (zh) 2020-08-03 2023-05-16 诺华股份有限公司 杂芳基取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途
US20240042051A1 (en) 2020-11-24 2024-02-08 Francesca Rocchetti Mcl-1 inhibitor antibody-drug conjugates and methods of use
CR20230283A (es) 2020-11-24 2023-07-27 Novartis Ag Anticuerpos anti-cd48, conjugados de anticuerpo-fármaco, y usos de los mismos
IL304891A (en) 2021-02-02 2023-10-01 Servier Lab Selective Protech BCL-XL compounds and methods of use
TW202304979A (zh) 2021-04-07 2023-02-01 瑞士商諾華公司 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途
AR125874A1 (es) 2021-05-18 2023-08-23 Novartis Ag Terapias de combinación
KR20230094172A (ko) * 2021-12-20 2023-06-27 주식회사 삼양홀딩스 용해도가 개선된 풀베스트란트의 약학 조성물 및 그 제조 방법
WO2023225336A1 (en) 2022-05-20 2023-11-23 Novartis Ag Met bcl-xl inhibitor antibody-drug conjugates and methods of use thereof
WO2023225320A1 (en) 2022-05-20 2023-11-23 Novartis Ag Epha2 bcl-xl inhibitor antibody-drug conjugates and methods of use thereof

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB817241A (en) 1957-08-21 1959-07-29 Vismara Francesco Spa Oily solutions for parenteral administration containing adreno-cortical hormones
FR6241E (fr) 1905-04-19 1906-10-10 Ktiengesellschaft Système de refroidissement du piston des moteurs à explosions et des compresseurs
DE947335C (de) 1954-10-19 1956-08-16 Schering Ag Verfahren zur Herstellung stabiler oeliger Loesungen von Oestron
US2983649A (en) 1957-10-15 1961-05-09 Francesco Vismara Societa Per Ricinoleic acid ester solutions of adreno-cortical hormones
GB1060632A (en) * 1962-09-11 1967-03-08 Olin Mathieson Steroid compositions
US3164520A (en) * 1962-10-29 1965-01-05 Olin Mathieson Injectable steroid compositions containing at least 75% benzyl benzoate
JPS4327327Y1 (da) 1965-01-07 1968-11-12
NL151903B (nl) 1965-03-24 1977-01-17 Schering Ag Werkwijze ter bereiding van een injectievloeistof door een steroid op te lossen in een mengsel van ricinusolie en benzylbenzoaat.
USRE28690E (en) * 1965-05-05 1976-01-20 Schering Aktiengesellschaft 17α-Ethinyl-18-methyl-19-nortestosterone esters
GB1207571A (en) * 1967-01-13 1970-10-07 Takeda Chemical Industries Ltd Injectable composition
SU549118A1 (ru) 1973-04-02 1977-03-05 Способ синхронизации половой охоты у циклирующих свиноматок
SU676284A1 (ru) 1975-06-26 1979-07-30 Научно-Исследовательский Институт Животноводства Способ синхронизации половой охоты у самок домашних животных
DE2548413A1 (de) 1975-10-27 1977-04-28 Schering Ag Depotpraeparate in oeliger ungesaettigter loesung zur intramuskulaeren injektion
US4048309A (en) 1976-02-24 1977-09-13 E. R. Squibb & Sons, Inc. Topical steroid ointment formulations
US4048310A (en) 1976-02-24 1977-09-13 E. R. Squibb & Sons, Inc. Topical steroid formulation in form of lotion or cream
NL7711916A (nl) * 1977-10-29 1979-05-02 Akzo Nv Werkwijze ter bereiding van sterk geconcen- treerde farmaceutische preparaten van steroiden.
FI65914C (fi) * 1978-03-07 1984-08-10 Sandoz Ag Foerfarande foer framstaellning av farmaceutiska kompositionerinnehaollande cyklosporin a
GB8327256D0 (en) 1983-10-12 1983-11-16 Ici Plc Steroid derivatives
DE3708942A1 (de) 1987-03-18 1988-09-29 Schering Ag 19,11ss-ueberbrueckte steroide, deren herstellung und diese enthaltende pharmazeutische praeparate
DE3733478A1 (de) 1987-10-01 1989-04-13 Schering Ag Antigestagen- und antioestrogenwirksame verbindungen zur geburtseinleitung und zum schwangerschaftsabbruch sowie zur behandlung gynaekologischer stoerungen und hormonabhaengiger tumore
EP0310542B1 (de) * 1987-10-01 1994-06-08 Schering Aktiengesellschaft Antigestagen- und antiöstrogenwirksame Verbindungen zur Behandlung hormonabhängiger Tumoren
GB8813353D0 (en) * 1988-06-06 1988-07-13 Ici Plc Therapeutic product
JPH04327327A (ja) 1991-04-25 1992-11-16 Toyoda Gosei Co Ltd スリーブとホースの加締め用ダイス
CN1102095A (zh) 1993-10-30 1995-05-03 浙江医科大学 长效雄激素类制剂——十一酸睾丸注射液
IL111991A (en) 1994-01-28 2000-07-26 Abbott Lab Liquid pharmaceutical composition of HIV protease inhibitors in organic solvent
ZA9510926B (en) * 1994-12-23 1996-07-03 Schering Ag Compounds with progesterone-antagonistic and antiestrogenic action to be used together for female contraception
US20010006963A1 (en) 1995-03-16 2001-07-05 Ursula Lachnit-Fixson Once-a-month injection as a depot contraceptive and for hormone replacement therapy for perimenopausal and premenopausal women
DE19510861A1 (de) 1995-03-16 1996-09-19 Schering Ag Einmonatsspritze als Depot-Kontrazeptivum und für die Hormonersatztherapie für peri- und praemenopausale Frauen
EP0760237A1 (en) 1995-08-30 1997-03-05 Cipla Limited Oil-in-water microemulsions
GB9525194D0 (en) * 1995-12-12 1996-02-07 Zeneca Ltd Pharmaceutical composition
JPH09208496A (ja) * 1996-01-30 1997-08-12 Takeda Chem Ind Ltd Ｌｈ−ｒｈ拮抗物質含有組成物
DE19613972A1 (de) 1996-04-09 1997-10-16 Bayer Ag Injektionsformulierungen von Avermectinen und Milbemycinen auf Basis von Rizinusöl
GB9608719D0 (en) 1996-04-26 1996-07-03 Scherer Ltd R P Pharmaceutical compositions
US5952338A (en) 1996-07-05 1999-09-14 Takeda Chemical Industries, Ltd. Agent for prophylaxis and treatment of disturbance of visual function
JPH10203982A (ja) * 1996-07-05 1998-08-04 Takeda Chem Ind Ltd 視機能障害の予防・治療剤
DE19635525A1 (de) * 1996-08-20 1998-02-26 Schering Ag 7alpha-(xi-Aminoalkyl)-estratriene, Verfahren zu deren Herstellung, pharmazeutische Präparate, die diese 7alpha(xi-Aminoalkyl-estratriene enthalten sowie deren Verwendung zur Herstellung von Arzneimitteln
DE19638045A1 (de) 1996-09-18 1998-03-19 Bayer Ag Injektionsformulierungen von Avermectinen und Milbemycinen
JPH10152438A (ja) * 1996-11-22 1998-06-09 Takeda Chem Ind Ltd １−アザキサントン誘導体またはその塩の安定化方法および１−アザキサントン誘導体含有組成物
US6191107B1 (en) 1997-09-26 2001-02-20 Takeda Chemical Industries, Ltd. Complex of human growth hormone and zinc
JPH11158200A (ja) * 1997-09-26 1999-06-15 Takeda Chem Ind Ltd ヒト成長ホルモン・亜鉛複合体及びその用途
WO1999027906A1 (en) 1997-12-03 1999-06-10 Merck & Co., Inc. Long acting injectable formulations containing hydrogenated castor oil
BRPI0009448B8 (pt) 1999-04-01 2021-05-25 Univ Texas kit para uso no tratamento de uma neoplasia em um mamífero
GB0000313D0 (en) 2000-01-10 2000-03-01 Astrazeneca Uk Ltd Formulation
JP4327327B2 (ja) 2000-04-03 2009-09-09 ロボテック株式会社 固定スプレー揺動装置
CN1553815A (zh) 2001-07-07 2004-12-08 用于肌内给药的氟维司群药物制剂
GB0912999D0 (en) 2009-07-27 2009-09-02 Astrazeneca Ab Method-803

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9271990B2 (en) 2014-02-14 2016-03-01 Fresenius Kabi Usa, Llc Fulvestrant formulations
US9833459B2 (en) 2014-02-14 2017-12-05 Fresenius Kabi Usa, Llc Fulvestrant formulations
US10188663B2 (en) 2014-02-14 2019-01-29 Fresenius Kabi Usa, Llc Fulvestrant formulations
US11229655B2 (en) 2014-02-14 2022-01-25 Fresenius Kabi Usa, Llc Fulvestrant formulations

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DK1250138T4 (da) 2015-07-27
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