WO2001035946A2 - Intranasal administration of raloxifene and tamoxifen - Google Patents

Intranasal administration of raloxifene and tamoxifen Download PDF

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Publication number
WO2001035946A2
WO2001035946A2 PCT/US2000/027394 US0027394W WO0135946A2 WO 2001035946 A2 WO2001035946 A2 WO 2001035946A2 US 0027394 W US0027394 W US 0027394W WO 0135946 A2 WO0135946 A2 WO 0135946A2
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Prior art keywords
raloxifene
tamoxifen
breast cancer
treatment
administered
Prior art date
Application number
PCT/US2000/027394
Other languages
French (fr)
Other versions
WO2001035946A3 (en
Inventor
Anwar A. Hussain
Lewis W. Dittert
Original Assignee
New Millennium Pharmaceutical Research, Inc.
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Filing date
Publication date
Application filed by New Millennium Pharmaceutical Research, Inc. filed Critical New Millennium Pharmaceutical Research, Inc.
Priority to AU79935/00A priority Critical patent/AU7993500A/en
Publication of WO2001035946A2 publication Critical patent/WO2001035946A2/en
Publication of WO2001035946A3 publication Critical patent/WO2001035946A3/en

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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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • This invention relates to novel methods of solubilization of raloxifene and tamoxifen and preparation of novel dosage forms of those drugs, which are suitable for intranasal administration.
  • Raloxifene and tamoxifen are anti-estrogens, which are commonly used in the palliative treatment of breast cancer. Doses of 10 to 20 mg of tamoxifen are commonly administered orally twice a day and 60 mg of raloxifene is generally administered orally once daily; however, since the drugs are used for breast pain (mastalgia), it would be advantageous to deliver them to the systemic circulation as rapidly as possible. Also, raloxifene and tamoxifen are very insoluble in water and are not reliably absorbed orally. The bioavailability of raloxifene is reported to be approximately 1 % due to insolubility and first-pass metabolism.
  • a major object of the present invention is to provide a method for safely and conveniently administering raloxifene or tamoxifen to a patient in need of prevention or treatment of breast cancer and/or mastalgia. A rapid and reliable response is achieved.
  • the method comprises the intranasal administration of an effective amount of raloxifene or tamoxifen to a patient suffering from, or at risk for, breast cancer and/or mastalgia.
  • the object of the present invention is to improve the rate of delivery of raloxifene or tamoxifen to the systemic circulation by administering raloxifene or tamoxifen via the nasal route in order to speed the onset of effect and reduce the dose required for its beneficial effect.
  • Intranasal delivery will improve drug bioavailability by direct absorption into the blood, thereby avoiding extensive first-pass metabolism which may significantly lower the plasma concentrations of raloxifene and tamoxifen when they are administered via the oral route.
  • raloxifene or tamoxifen can be administered which will result in fewer side effects, and the drug will be more tolerable and more effective in patients suffering from breast cancer and/or mastalgia.
  • raloxifene and tamoxifen are rapidly effective following intranasal administration, establishment of an ideal dose for a particular patient is greatly facilitated.
  • Intranasal dosage forms containing raloxifene or tamoxifen in combination with other drugs used in the treatment of breast cancer may also be employed in the practice of the present invention.
  • the present inventors have discovered a novel method for the delivery of raloxifene or tamoxifen, or derivatives thereof, to a patient in need of such treatment comprising administration of raloxifene or tamoxifen.
  • This method offers significant clinical advantages over the prior art. More specifically, the inventors sought to provide a rapid, reliable, safe, effective and convenient treatment for breast cancer comprising administering raloxifene or tamoxifen to a patient in need of such treatment, which comprises the administration of raloxifene or tamoxifen intranasally, thus providing a rapid therapeutic effect compared to prior art methods of treatment of breast cancer and/or mastalgia while avoiding the side-effects associated with oral dosage forms.
  • raloxifene or tamoxifen can be administered through the nasal route, thus resulting in fewer side effects.
  • the drugs will be better tolerated by the patient with less side effects and more effective in treating patients suffering from breast cancer and/or mastalgia.
  • the present invention concerns the intranasal administration of raloxifene or tamoxifen, which have the chemical structures set forth below
  • a pharmaceutical composition intended for nasal administration comprising at least one of said compounds.
  • a pharmaceutically acceptable ester thereof is envisioned.
  • One of the objects of the present invention is a method for increasing the aqueous solubility of raloxifene and/or tamoxifen or a derivative thereof to allow the preparation of pharmaceutically acceptable nasal dosage forms of the drugs which are suitable for intranasal administration to women suffering from breast cancer, especially those requiring relief from mastalgia.
  • raloxifene or tamoxifen may be administered either as a free base, or in the form of a pharmaceutically acceptable salt thereof.
  • Pharmaceutically acceptable salts of the compounds of formula (I) which contain a basic center are, for example, non-toxic acid addition salts formed with inorganic acids such as hydrochloric, hydrobromic, sulphuric and phosphoric acid, with organo- carboxylic acids, for example, gluconate or with organo-sulphonic acids, for example, mesylate.
  • Preferred salts of raloxifene and tamoxifen must be soluble in water and have other physical properties that are desirable for an elegant pharmaceutical formulation with improved bioavailability, such preferred salts include methanesulfonate (mesylate), gluconate, ascorbate, lactate, acetate and citrate.
  • the intranasal composition of the present invention is useful in the treatment of a mammalian organism, especially a female mammal, including animals and humans.
  • the term "patient” will encompass any mammal requiring treatment with raloxifene or tamoxifen, or derivatives thereof, particularly a human patient, especially a female, suffering from breast cancer and the associated mastalgia.
  • a still further aspect of this invention is a pharmaceutical composition of matter that comprises raloxifene or tamoxifen, or derivatives thereof, as described above, and/or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable carriers therefor.
  • raloxifene or tamoxifen or salts thereof can be conveniently administered in the form of a pharmaceutical composition containing raloxifene or tamoxifen, or a salt thereof, and a pharmaceutically acceptable intranasal carrier therefor.
  • the carrier may be a liquid, solution, spray, drops, gel, or combination thereof.
  • the carrier is a pharmaceutically acceptable aqueous solution.
  • Such compositions may require the use of one or more solubilizing agents to both effect dissolution of the drug(s) and/or keep them in aqueous solution. Suitable applications of solubilizing agents are exemplified below.
  • the preferred dosage forms are a nasal spray, for rapid absorption and rapid onset of beneficial effects, and a nasal gel, typically for more prolonged effects.
  • Raloxifene or tamoxifen or their salts may be formulated together with the carrier into any desired unit dosage form.
  • Unit dosage forms such as solutions, suspensions, and water-miscible semisolids are particularly preferred.
  • Each carrier must be “acceptable” in the sense of being compatible with the other ingredients in the formulation and not injurious to the patient.
  • the carrier must be biologically acceptable and inert and suitable for intranasal administration.
  • suitable buffers are included in the carriers to maintain the pH within the limits required to keep the drugs in solution.
  • solutions typically are buffered in the acidic pH range (approximately 2 to 6)
  • solutions typically are buffered in the alkaline pH range (approximately 8 to 12).
  • solutions and suspensions are sterilized and are preferably isotonic to blood.
  • the dosage of raloxifene or tamoxifen or pharmaceutically acceptable salts thereof in the compositions of the invention will vary depending on several factors, including, but not limited to, the age, weight, and species of the patient, the general health of the patient, the severity of the symptoms, whether the composition is being administered alone or in combination with other agents, the incidence of side effects and the like.
  • the desired dose may be administered as needed, and may be administered repeatedly over a period of months or years. Higher and lower doses may also be administered.
  • a major advantage of the present invention is the extremely rapid onset of response, which enables the physician to adjust the dose to produce only the desired effects and nothing more, thereby optimizing drug use and minimizing side-effects.
  • the daily dose may be adjusted taking into account, for example, the above-identified variety of parameters.
  • tamoxifen may be administered in an amount of up to about 50 mg/dose.
  • the amount of raloxifene administered will not exceed 30 mg/dose.
  • the typical range is 10 to 50 mg/dose, preferably 10 to 40 mg/dose.
  • the dose is usually administered once or twice daily.
  • the maximum daily dose is approximately 100 mg.
  • other amounts may also be administered, in particular, much smaller amounts of raloxifene will be required when administered intranasally, in accordance with the present invention.
  • raloxifene may be administered in an amount of up to about 120 mg/dose.
  • the dose is usually administered once daily.
  • the amount of raloxifene administered will not exceed 60 mg/dose.
  • the typical range is 30 to 120 mg/dose, preferably 30 to 60 mg/dose.
  • other amounts may also be administered, in particular, much smaller amounts of tamoxifen will be required when administered intranasally, in accordance with the present invention.
  • the active ingredient While it is possible for the active ingredient to be administered alone, as noted above, it is preferably present as a pharmaceutical formulation.
  • the formulations of the present invention comprise at least one active ingredient, as defined above, together with one or more acceptable carriers thereof and optionally other therapeutic agents.
  • the method of the present invention may be practiced by administration of raloxifene or tamoxifen by themselves or in a combination with other active ingredients in a pharmaceutical composition.
  • Other therapeutic agents suitable for use herein are any compatible drugs that are effective by the same or other mechanisms for the intended purpose, or drugs that are complementary to those of raloxifene and tamoxifen.
  • additional drugs include, but are not limited to, those drugs mentioned above.
  • the compounds utilized in combination therapy may be administered simultaneously, in either separate or combined formulations, or at different times than the raloxifene or tamoxifen, e.g., sequentially, such that a combined effect is achieved.
  • the amounts and regime of administration will be adjusted by the practitioner, by preferably initially lowering their standard doses and then titrating the results obtained.
  • the therapeutic method of the invention may be used in conjunction with other therapies as determined by the practitioner.
  • the sodium mesylate is dissolved in the water and the raloxifene HCI is added and dissolved with stirring.
  • the solution is placed in a nasal administrator designed to deliver 100 ⁇ of spray for each application.
  • One spray in each nostril will deliver a total of 10 mg of raloxifene HCI.

Abstract

This invention provides a method of rapidly and reliably delivering raloxifene or tamoxifen, or derivatives thereof, alone or in combination with other compounds, to the systemic circulation by administration via the nasal route to produce rapid onset of beneficial effects in the treatment or prevention of breast cancer. The present invention further provides intranasal pharmaceutical compositions comprising raloxifene or tamoxifen, or derivatives thereof, and/or pharmaceutically acceptable salts thereof in a variety of unique pharmaceutical dosage forms, with and without other compounds.

Description

INTRANASAL ADMINISTRATION OF RALOXIFENE AND TAMOXIFEN
BACKGROUND OF THE INVENTION
1. Field of the Invention This invention relates to novel methods of solubilization of raloxifene and tamoxifen and preparation of novel dosage forms of those drugs, which are suitable for intranasal administration.
2. Description of the Related Art Raloxifene and tamoxifen are anti-estrogens, which are commonly used in the palliative treatment of breast cancer. Doses of 10 to 20 mg of tamoxifen are commonly administered orally twice a day and 60 mg of raloxifene is generally administered orally once daily; however, since the drugs are used for breast pain (mastalgia), it would be advantageous to deliver them to the systemic circulation as rapidly as possible. Also, raloxifene and tamoxifen are very insoluble in water and are not reliably absorbed orally. The bioavailability of raloxifene is reported to be approximately 1 % due to insolubility and first-pass metabolism.
While treatment for cancer requires urgency in treatment, a rapid beneficial therapeutic effect is most important when the patient is uncomfortable or in pain. Breast cancer is oftentimes associated with mastalgia and in the treatment of pain, time is of the essence. A rapid, reliable onset of effect is highly desirable for treatment to be considered optimal. And while raloxifene and tamoxifen are useful in the prevention and treatment of breast cancer their therapeutic impact takes on special urgency in the treatment of pain.
Therefore, in view of the aforementioned deficiencies attendant with the prior art methods for the treatment of breast cancer using raloxifene and tamoxifen, it should be apparent that there still exists a need in the art for a rapid, reliable, safe and convenient method of administering raloxifene or tamoxifen in the treatment of breast cancer.
SUMMARY OF THE INVENTION A major object of the present invention is to provide a method for safely and conveniently administering raloxifene or tamoxifen to a patient in need of prevention or treatment of breast cancer and/or mastalgia. A rapid and reliable response is achieved. The method comprises the intranasal administration of an effective amount of raloxifene or tamoxifen to a patient suffering from, or at risk for, breast cancer and/or mastalgia.
The object of the present invention is to improve the rate of delivery of raloxifene or tamoxifen to the systemic circulation by administering raloxifene or tamoxifen via the nasal route in order to speed the onset of effect and reduce the dose required for its beneficial effect. Intranasal delivery will improve drug bioavailability by direct absorption into the blood, thereby avoiding extensive first-pass metabolism which may significantly lower the plasma concentrations of raloxifene and tamoxifen when they are administered via the oral route. As a result, small doses of raloxifene or tamoxifen, or derivatives thereof, can be administered which will result in fewer side effects, and the drug will be more tolerable and more effective in patients suffering from breast cancer and/or mastalgia. Further, since raloxifene and tamoxifen are rapidly effective following intranasal administration, establishment of an ideal dose for a particular patient is greatly facilitated. Intranasal dosage forms containing raloxifene or tamoxifen in combination with other drugs used in the treatment of breast cancer may also be employed in the practice of the present invention.
With the foregoing and other objects, advantages and features of the invention that will become hereinafter apparent, the nature of the invention is further explained in the following detailed description of the preferred embodiments of the invention and in the appended claims.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
Thus, the present inventors have discovered a novel method for the delivery of raloxifene or tamoxifen, or derivatives thereof, to a patient in need of such treatment comprising administration of raloxifene or tamoxifen. This method offers significant clinical advantages over the prior art. More specifically, the inventors sought to provide a rapid, reliable, safe, effective and convenient treatment for breast cancer comprising administering raloxifene or tamoxifen to a patient in need of such treatment, which comprises the administration of raloxifene or tamoxifen intranasally, thus providing a rapid therapeutic effect compared to prior art methods of treatment of breast cancer and/or mastalgia while avoiding the side-effects associated with oral dosage forms. Specifically, smaller doses of raloxifene or tamoxifen can be administered through the nasal route, thus resulting in fewer side effects. By using the method of the present invention, which produces a rapid response, the drugs will be better tolerated by the patient with less side effects and more effective in treating patients suffering from breast cancer and/or mastalgia.
More particularly, the present invention concerns the intranasal administration of raloxifene or tamoxifen, which have the chemical structures set forth below
Figure imgf000005_0001
RALOXIFENE TAMOXIFEN
or a derivative thereof and/or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition intended for nasal administration comprising at least one of said compounds. In addition, in the case of raloxifene or a derivative thereof, a pharmaceutically acceptable ester thereof is envisioned.
One of the objects of the present invention is a method for increasing the aqueous solubility of raloxifene and/or tamoxifen or a derivative thereof to allow the preparation of pharmaceutically acceptable nasal dosage forms of the drugs which are suitable for intranasal administration to women suffering from breast cancer, especially those requiring relief from mastalgia.
According to the present invention, raloxifene or tamoxifen may be administered either as a free base, or in the form of a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts of the compounds of formula (I) which contain a basic center are, for example, non-toxic acid addition salts formed with inorganic acids such as hydrochloric, hydrobromic, sulphuric and phosphoric acid, with organo- carboxylic acids, for example, gluconate or with organo-sulphonic acids, for example, mesylate. Preferred salts of raloxifene and tamoxifen must be soluble in water and have other physical properties that are desirable for an elegant pharmaceutical formulation with improved bioavailability, such preferred salts include methanesulfonate (mesylate), gluconate, ascorbate, lactate, acetate and citrate.
The intranasal composition of the present invention is useful in the treatment of a mammalian organism, especially a female mammal, including animals and humans.
According to the present invention, the term "patient" will encompass any mammal requiring treatment with raloxifene or tamoxifen, or derivatives thereof, particularly a human patient, especially a female, suffering from breast cancer and the associated mastalgia. A still further aspect of this invention is a pharmaceutical composition of matter that comprises raloxifene or tamoxifen, or derivatives thereof, as described above, and/or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable carriers therefor.
For therapeutic use in the prevention or treatment of breast cancer, raloxifene or tamoxifen or salts thereof, can be conveniently administered in the form of a pharmaceutical composition containing raloxifene or tamoxifen, or a salt thereof, and a pharmaceutically acceptable intranasal carrier therefor.
Typically, the carrier may be a liquid, solution, spray, drops, gel, or combination thereof. In a preferred embodiment, the carrier is a pharmaceutically acceptable aqueous solution. Such compositions may require the use of one or more solubilizing agents to both effect dissolution of the drug(s) and/or keep them in aqueous solution. Suitable applications of solubilizing agents are exemplified below. The preferred dosage forms are a nasal spray, for rapid absorption and rapid onset of beneficial effects, and a nasal gel, typically for more prolonged effects.
Raloxifene or tamoxifen or their salts may be formulated together with the carrier into any desired unit dosage form. Unit dosage forms such as solutions, suspensions, and water-miscible semisolids are particularly preferred.
Each carrier must be "acceptable" in the sense of being compatible with the other ingredients in the formulation and not injurious to the patient. The carrier must be biologically acceptable and inert and suitable for intranasal administration. In most cases, suitable buffers are included in the carriers to maintain the pH within the limits required to keep the drugs in solution. For example, for drugs containing a basic center, solutions typically are buffered in the acidic pH range (approximately 2 to 6), and for drugs containing an acidic center, solutions typically are buffered in the alkaline pH range (approximately 8 to 12). To prepare formulations suitable for intranasal administration, solutions and suspensions are sterilized and are preferably isotonic to blood.
The dosage of raloxifene or tamoxifen or pharmaceutically acceptable salts thereof in the compositions of the invention will vary depending on several factors, including, but not limited to, the age, weight, and species of the patient, the general health of the patient, the severity of the symptoms, whether the composition is being administered alone or in combination with other agents, the incidence of side effects and the like. The desired dose may be administered as needed, and may be administered repeatedly over a period of months or years. Higher and lower doses may also be administered. A major advantage of the present invention is the extremely rapid onset of response, which enables the physician to adjust the dose to produce only the desired effects and nothing more, thereby optimizing drug use and minimizing side-effects.
The daily dose may be adjusted taking into account, for example, the above-identified variety of parameters. Typically, tamoxifen may be administered in an amount of up to about 50 mg/dose. Preferably, the amount of raloxifene administered will not exceed 30 mg/dose. The typical range is 10 to 50 mg/dose, preferably 10 to 40 mg/dose. The dose is usually administered once or twice daily. The maximum daily dose is approximately 100 mg. However, other amounts may also be administered, in particular, much smaller amounts of raloxifene will be required when administered intranasally, in accordance with the present invention.
Typically, raloxifene may be administered in an amount of up to about 120 mg/dose. The dose is usually administered once daily. Preferably, the amount of raloxifene administered will not exceed 60 mg/dose. The typical range is 30 to 120 mg/dose, preferably 30 to 60 mg/dose. However, other amounts may also be administered, in particular, much smaller amounts of tamoxifen will be required when administered intranasally, in accordance with the present invention.
While it is possible for the active ingredient to be administered alone, as noted above, it is preferably present as a pharmaceutical formulation. The formulations of the present invention comprise at least one active ingredient, as defined above, together with one or more acceptable carriers thereof and optionally other therapeutic agents.
The method of the present invention may be practiced by administration of raloxifene or tamoxifen by themselves or in a combination with other active ingredients in a pharmaceutical composition. Other therapeutic agents suitable for use herein are any compatible drugs that are effective by the same or other mechanisms for the intended purpose, or drugs that are complementary to those of raloxifene and tamoxifen. Such additional drugs include, but are not limited to, those drugs mentioned above.
The compounds utilized in combination therapy may be administered simultaneously, in either separate or combined formulations, or at different times than the raloxifene or tamoxifen, e.g., sequentially, such that a combined effect is achieved. The amounts and regime of administration will be adjusted by the practitioner, by preferably initially lowering their standard doses and then titrating the results obtained. The therapeutic method of the invention may be used in conjunction with other therapies as determined by the practitioner. Having now generally described this invention, the same will be better understood by reference to certain specific examples, which are included herein for purposes of illustration only and are not intended to be limiting of the invention or any embodiment thereof, unless so specified. Set forth below are examples of experimental procedures designed to demonstrate the features of this invention in mammalian models, and examples of pharmaceutical dosage forms that embody and illustrate its reduction to practice.
EXAMPLE 1: NASAL SPRAY SOLUTION
Raloxifene HCI 1500 mg
Sodium Mesylate 2000 mg
Distilled Water 30 ml
The sodium mesylate is dissolved in the water and the raloxifene HCI is added and dissolved with stirring. The solution is placed in a nasal administrator designed to deliver 100 μ\ of spray for each application. One spray in each nostril will deliver a total of 10 mg of raloxifene HCI.
EXAMPLE 2: NASAL GEL (AQUEOUS)
Tamoxifen Citrate 5 grams
Sodium Mesylate 5 grams
Methocel 3 grams
Distilled Water 100 grams
Approximately 70 grams of water is heated to 80°C, and the methocel is dispersed in the water with stirring. The sodium mesylate is dissolved in 30 grams of water, and the tamoxifen citrate is added and dissolved with stirring. The resulting solution is heated to 80°C and mixed with the methocel dispersion. The resultant mixture is allowed to stand at room temperature for 3 hours. The gel is placed in an ointment tube equipped with a fine orifice and is applied in the nasal nares with a finger or cotton tipped applicator.
While the invention has been described and illustrated herein by references to various specific material, procedures and examples, it is understood that the invention is not restricted to the particular material, combinations of material, and procedures selected for that purpose.
Numerous variations of such details can be implied and will be appreciated by those skilled in the art.

Claims

WHAT IS CLAIMED IS:
1. A method for preventing or treating breast cancer, said method comprising intranasally administering to a patient in need of such prevention or treatment an effective amount of a pharmaceutical composition comprising raloxifene or tamoxifen, or a derivative thereof, or a pharmaceutically acceptable salt thereof, along with a pharmaceutically acceptable nasal carrier therefor.
2. The method according to claim 1 , wherein the carrier is aqueous.
3. The method according to claim 1 , wherein raloxifene is intranasally administered.
4. The method according to claim 1 , wherein tamoxifen is intranasally administered.
5. An intranasal pharmaceutical composition suitable for the prevention or treatment of breast cancer, comprising an effective amount of raloxifene or tamoxifen, or a derivative thereof, to prevent or treat breast cancer along with a pharmaceutically acceptable nasal carrier therefor.
6. The composition according to claim 5, wherein the carrier is aqueous.
7. The composition according to claim 5, which is in the form of a liquid, solution, spray, drops or gel.
PCT/US2000/027394 1999-11-15 2000-10-05 Intranasal administration of raloxifene and tamoxifen WO2001035946A2 (en)

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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996009040A1 (en) * 1994-09-20 1996-03-28 Eli Lilly And Company Benzofuran compounds, compositions, and methods
EP0747054A2 (en) * 1995-06-06 1996-12-11 Eli Lilly And Company Methods for minimizing bone loss
EP0838464A1 (en) * 1996-10-25 1998-04-29 Eli Lilly And Company Substituted benzo(b)thiophene compounds having activity as selective estrogen receptor modulators
WO1998029114A1 (en) * 1996-12-30 1998-07-09 Bar-Ilan University Tricarboxylic acid-containing oxyalkyl esters and uses thereof
EP0897722A1 (en) * 1997-08-21 1999-02-24 Eli Lilly And Company Benzo(b)thiophene derivatives for inhibiting fibrous inflammatory diseases and Riedel's thyroiditis
WO1999051096A1 (en) * 1998-04-08 1999-10-14 Eli Lilly And Company Pulmonary and nasal delivery of raloxifene
WO1999062537A1 (en) * 1998-06-04 1999-12-09 The Rockefeller University Methods and agents for modulating the immune response and inflammation involving monocyte and dendritic cell membrane proteins
WO2000059517A1 (en) * 1999-04-07 2000-10-12 Roger Williams Hospital Ceramide and chemotherapeutic agents for inducing cell death

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996009040A1 (en) * 1994-09-20 1996-03-28 Eli Lilly And Company Benzofuran compounds, compositions, and methods
EP0747054A2 (en) * 1995-06-06 1996-12-11 Eli Lilly And Company Methods for minimizing bone loss
EP0838464A1 (en) * 1996-10-25 1998-04-29 Eli Lilly And Company Substituted benzo(b)thiophene compounds having activity as selective estrogen receptor modulators
WO1998029114A1 (en) * 1996-12-30 1998-07-09 Bar-Ilan University Tricarboxylic acid-containing oxyalkyl esters and uses thereof
EP0897722A1 (en) * 1997-08-21 1999-02-24 Eli Lilly And Company Benzo(b)thiophene derivatives for inhibiting fibrous inflammatory diseases and Riedel's thyroiditis
WO1999051096A1 (en) * 1998-04-08 1999-10-14 Eli Lilly And Company Pulmonary and nasal delivery of raloxifene
WO1999062537A1 (en) * 1998-06-04 1999-12-09 The Rockefeller University Methods and agents for modulating the immune response and inflammation involving monocyte and dendritic cell membrane proteins
WO2000059517A1 (en) * 1999-04-07 2000-10-12 Roger Williams Hospital Ceramide and chemotherapeutic agents for inducing cell death

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