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US3164520A - Injectable steroid compositions containing at least 75% benzyl benzoate - Google Patents

Injectable steroid compositions containing at least 75% benzyl benzoate Download PDF

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Publication number
US3164520A
US3164520A US233931A US23393162A US3164520A US 3164520 A US3164520 A US 3164520A US 233931 A US233931 A US 233931A US 23393162 A US23393162 A US 23393162A US 3164520 A US3164520 A US 3164520A
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Prior art keywords
benzyl benzoate
testosterone
solution
vehicle
employed
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US233931A
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Huber Raymond Charles
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Olin Corp
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Olin Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—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
    • 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
    • A61K31/568—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • 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
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone

Definitions

  • compositions of matter and more particularly to new parenterally administrable pharmaceutical compositions comprising one or more active medicaments and a physiologically acceptable non-toxic pharmaceutical vehicle, comprised essentially of benzyl benzoate.
  • the active medicament which may be incorporat d in the novel compositions of this invention may be any one which is administered for use in comparatively large unit dosages, for example, rug/ml. to 500 mg./ml. and which is soluble in benz yl benzoate.
  • the medicaments which may be employed in this invention include inter alia, steroid hormones, especially those steroid hormones which exhibit anabolic, estrogenic, androgenic and progestational activity, for example, l7-hydroxyprogesterone and the esters thereof, testosterone, estradiol and the acid esters thereof, progesterone and its derivatives and A testololactone and its derivatives.
  • the active medicament is a steroid hormone although other pharmaceutically active compounds may also be employed, with satisfactory results.
  • the amount of benzyl benzoate which may be employed in thecompositions of this invention while still yielding satisfactory results has been found to range from about to by volume of the pharmaceutical vehicle employed.
  • the ratio of benzyl benzoate present in the pharmaceutical vehicle as compared to any other ingredients therein must be at least 3 to 1.
  • a pharmaceutical vehicle consisting essentially of pure benzyl benzoate yields the best results although at lower'levels satisfactory results are also obtained.
  • additives such as preservatives, antioxidants or anesthetics, such as benzyl alcohol and the other like well known additives may also be included in the pharmaceutical compositions of this invention.
  • preservatives such as benzyl alcohol and the other like well known additives
  • benzyl alcohol and the other like well known additives may also be included in the pharmaceutical compositions of this invention.
  • their use herein is permissive and not mandatory as their incorporation or omission in the final product of this invention does not substantially affect the results herein obtained.
  • compositions of this invention are easily prepared by merely taking the desired amount of medicament and dissolving it in the pharmaceutical vehicle of this invention by any means known in the art, for example, by mere stirring.
  • compositions of this invention are parenterally administrable to the animal being treated.
  • the administration of the composition may be accomplished intramuscularly, subcutaneously or in any other manner known to the art as may be determined in the individual cases wherein this invention is employed. It has been generally found that the most preferable results are obtained when an intramuscular route of administration is employed, although other methods of administration will also give satisfactory results.
  • Example 1 Two g. of the acetophenone derivative of 16,17-dihydroxyprogesterone are dissolved in 10 ml. of benzyl benzoate with stirring and warming. The resultant solution is then filled in vials of 5 ml. each and sterilized by autoclaving at 121 C. for two hours.
  • ⁇ Vhen 2 g. of the acetophenone derivative of 16,17-dihydroxyprogesterone are dissolved in 4.5 ml. of benzyl benzoate and 5.5 ml. of castor oil in accordance with the procedure of Example 1 and 0.25 ml. of the resultant solution is injected intramuscularly into the rabbit a lesion at the site of injection having a size of 967 cubic millimeters after two days.
  • Example 2 The procedure of Example 1 is followed except that 2 g. of testosterone palmitate are substituted for the acetophenone derivative of l6,l7-dihydroxyprogesterone of Example 1.
  • Example 3 A 25% solution of progesterone is prepared by dissolving 2.5 g. of progesterone in benzyl benzoate to make 10 ml. Sterilization is obtained by autoclaving the solution at 121 C. for 2 hours. When 0.25 mg. of this solution is injected into the vastus lateralis muscle of the rabbit, a lesion is produced which, after 2 days, measures 672 cubic millimeters.
  • Example 4 A 50% solution of hormones is'prepared by dissolving 2.5 g. of progesterone and 2.5 g. of l7-hydroxyprogesterone caproate in benzyl benzoate to make 10 ml. of final After autoclaving at 121 C. for 2 hours to sterilize, 0.25 ml. of the solution is injected into a rabbit muscle and the lesion size is measured after 2 days. A lesion consisting of 572 cubic millimeters was produced. When this same hormone combination in the same proportions Was dissolved in a vehicle consisting of 46% benzyl benzoate and 54% castor oil, a rabbit muscle lesion size of 1047 cubic millimeters is produced 2 days after injection of 0.25 ml. of test material.
  • Example A 40% solution of testosterone enanthate is prepared :by dissolving 4.0 g. in benzyl benzoate to make ml. of final volume. After autoclaving at 121 C. for 2 hours to sterilize, 0.25 ml. of the solution is injected into the vastus lateralis muscle of the rabbit and the lesion size is measured after 2 days. A lesion consisting of 847 cubic millimeters is produced.
  • Example 6 A 5% solution ofA btestololaetone is prepared by dissolving 50 mg/ml. in benzyl benzoate and after autoclaving to sterilize, 0.25 ml. of the solution is injected I
  • Example 7 15 mg. of A -testo-lolactone is dissolved in a solution comprised of 7.5 ml. of benzyl benzoate and 2.5 ml. of castor oil.
  • the resultant solution is sterilized, then filled in vials of 5 ml. each and sterilized by autoclaving at 121 C. for 2 hours.
  • the injectable solution may then be administered to the patient being treated.
  • a parenterally administrable pharmaceutical composition comprising the acetophenonide of 16,17-dihydroxyprogesterone and a physiologically acceptable nontoxic pharmaceutical vehicle wherein at least by volume of said vehicle is benzyl benzoate.
  • a parenterally administrable pharmaceutical composition comprising testosterone palmitate and a physiologically acceptable non-toxis pharmaceutical vehicle wherein at least 75% by volume of said vehicle is benzyl benzoate.
  • a parenterally administrable pharmaceutical composition co-mprising testosterone enanthate and a physiologically acceptable non-toxic pharmaceutical vehicle wherein at least 75 by volume of said vehicle is benzyl benzoate.
  • a method of administering a large single dosage of a steroid which comprises parenterally administering to the patient being treated a composition comprising a steroid selected from the group consisting of 17-hydroxyprogesterone, the caproate ester of 17-hydroxyprogesterone, testosterone, the enanthate ester of testosterone, the palmitate ester of testosterone, estradiol, progesterone, and A -testololactone, and a pharmaceutical carrier, said carrier being at least 75% by volume of benzyl benzoate.

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

Description

a 164 520 INJECTABLE srnnoni coMrosmoNs CONTAIN- ING AT LEAST 75% smart. BENZOATE Raymond Charles Huber, Martinsville, N.J., assignor to Ser. No. 233,931 4 Claims.
This invention relates to compositions of matter and more particularly to new parenterally administrable pharmaceutical compositions comprising one or more active medicaments and a physiologically acceptable non-toxic pharmaceutical vehicle, comprised essentially of benzyl benzoate.
The active medicament which may be incorporat d in the novel compositions of this invention may be any one which is administered for use in comparatively large unit dosages, for example, rug/ml. to 500 mg./ml. and which is soluble in benz yl benzoate. Examples of the medicaments which may be employed in this invention include inter alia, steroid hormones, especially those steroid hormones which exhibit anabolic, estrogenic, androgenic and progestational activity, for example, l7-hydroxyprogesterone and the esters thereof, testosterone, estradiol and the acid esters thereof, progesterone and its derivatives and A testololactone and its derivatives. In the most preferable embodiment of this invention the active medicament is a steroid hormone although other pharmaceutically active compounds may also be employed, with satisfactory results.
Heretofore it has been well recognized in the preparation of. parenterally administrable pharmaceutical compositions that a suitable solvent must be employed to render the composition injectable. However, as the science of medicine has progressed it has been found that increasingly higher dosages of certain medicaments must be employed in the treatment of certain ailments in order to achieve several advantages. Among these advantages can be numbered the prolongation of activity of the medicaments involved and the lessening of the total number of individual injections which are needed to obtain the same results.
Additionally, it has been found that new chemical modifications of medicaments are continually being discovered and the solubility of these modified medicaments in the solvents commonly employed, appears to be more and more limited and it has therefore become increasingly difficult to dissolve these new modified medicaments in parenterally acceptable vehicles. It is well-known that certain pharmamutical vehicles'yield satisfactory results at low level medicament concentrations when employed in compositions for parenteral administration. Such vehicles are the vegetable oils such as cotton seed oil, peanut oil, sesame oil, or corn oil, in combination with small amounts of benzyl benzoate. However, when an increased dosage level of the medicaments is employed, along with a correspondingly necessary increased amount of pharmaceutical vehicle it has been found that certain undesirable disadvantages exist. j
The undesirable disadvantages which are present when the prior art vehicles are employed with a high dosage level of medicaments, are many. In addition to the prior art vehicles being incapable of solubilizing any great quantities of the medicaments, it has been found that the compositions heretofore employed produce an undue amount of irritation at the site of injection, when parenterally administered into the animal being treated.
It has now been found that the disadvantages encountered in the parenteral administration of high dosage levels of the medicaments of this invention can be avoided by employing the novel pharmaceutical compositions of United States Patent 0 Fr ice this invention. It has been found that these disadvantages can be overcome by employing benzyl benzoate as the essential component of the pharmaceutical vehicle of parenterally administrable compositions. The benzyl benzoate has been found to be capable of dissolving great quantities of the medicaments of this invention and the resulting parenterally administrable composition employing this vehicle does not produce undue irritation when injected into the animals being treated.
The amount of benzyl benzoate which may be employed in thecompositions of this invention while still yielding satisfactory results has been found to range from about to by volume of the pharmaceutical vehicle employed. Thus the ratio of benzyl benzoate present in the pharmaceutical vehicle as compared to any other ingredients therein must be at least 3 to 1. In the most preferable embodiment of this invention it has been found that a pharmaceutical vehicle consisting essentially of pure benzyl benzoate yields the best results although at lower'levels satisfactory results are also obtained.
As is common in the art of preparing parenterally administrable pharmaceutical compositions other additives such as preservatives, antioxidants or anesthetics, such as benzyl alcohol and the other like well known additives may also be included in the pharmaceutical compositions of this invention. However, their use herein is permissive and not mandatory as their incorporation or omission in the final product of this invention does not substantially affect the results herein obtained.
The compositions of this invention are easily prepared by merely taking the desired amount of medicament and dissolving it in the pharmaceutical vehicle of this invention by any means known in the art, for example, by mere stirring.
The final compositions of this invention are parenterally administrable to the animal being treated. The administration of the composition may be accomplished intramuscularly, subcutaneously or in any other manner known to the art as may be determined in the individual cases wherein this invention is employed. It has been generally found that the most preferable results are obtained when an intramuscular route of administration is employed, although other methods of administration will also give satisfactory results.
The invention is more particularly illustrated by the following examples:
Example 1 Two g. of the acetophenone derivative of 16,17-dihydroxyprogesterone are dissolved in 10 ml. of benzyl benzoate with stirring and warming. The resultant solution is then filled in vials of 5 ml. each and sterilized by autoclaving at 121 C. for two hours.
0.25 ml. of the resulting solution is then injected into the vastus lateralis muscle of a rabbit producing a lesion at the'site of the injection having the size of about 640 cubic millimeters after two days.
\Vhen 2 g. of the acetophenone derivative of 16,17-dihydroxyprogesterone are dissolved in 4.5 ml. of benzyl benzoate and 5.5 ml. of castor oil in accordance with the procedure of Example 1 and 0.25 ml. of the resultant solution is injected intramuscularly into the rabbit a lesion at the site of injection having a size of 967 cubic millimeters after two days.
Example 2 The procedure of Example 1 is followed except that 2 g. of testosterone palmitate are substituted for the acetophenone derivative of l6,l7-dihydroxyprogesterone of Example 1.
0.25 ml. of the resultant solution is injected intramusproduct.
aroma-o cularly into a rabbit producing a lesion at the site of injection having the size of about 420 cubic millimeters after two days. When 2 g. of testosterone palmitate are dissolved in a vehicle consisting of 40% castor oil and 60% benzyl benzoate and the resultant solution is injected intramuscularly into the rabbit, a lesion at the site of injection having a size of 610 cubic millimeters is produced after two days.
Example 3 A 25% solution of progesterone is prepared by dissolving 2.5 g. of progesterone in benzyl benzoate to make 10 ml. Sterilization is obtained by autoclaving the solution at 121 C. for 2 hours. When 0.25 mg. of this solution is injected into the vastus lateralis muscle of the rabbit, a lesion is produced which, after 2 days, measures 672 cubic millimeters.
When 2.5 g. of progesterone are dissolved to make 10 ml. in a mixture of 50% benzyl benzoate and 50% castor oil as the vehicle, and 0.25 ml. of this solution is injected into the rabbit muscle, a lesion size of 898 cubic millimeters is produced after two days.
Example 4 A 50% solution of hormones is'prepared by dissolving 2.5 g. of progesterone and 2.5 g. of l7-hydroxyprogesterone caproate in benzyl benzoate to make 10 ml. of final After autoclaving at 121 C. for 2 hours to sterilize, 0.25 ml. of the solution is injected into a rabbit muscle and the lesion size is measured after 2 days. A lesion consisting of 572 cubic millimeters was produced. When this same hormone combination in the same proportions Was dissolved in a vehicle consisting of 46% benzyl benzoate and 54% castor oil, a rabbit muscle lesion size of 1047 cubic millimeters is produced 2 days after injection of 0.25 ml. of test material.
Example A 40% solution of testosterone enanthate is prepared :by dissolving 4.0 g. in benzyl benzoate to make ml. of final volume. After autoclaving at 121 C. for 2 hours to sterilize, 0.25 ml. of the solution is injected into the vastus lateralis muscle of the rabbit and the lesion size is measured after 2 days. A lesion consisting of 847 cubic millimeters is produced. I
When this same quantity of hormone is dissolved in a vehicle consisting of benzyl benzoate and 80% sesame oil and 0.25 ml. is injected a lesion size of 1441 cubic millimeters is produced.
Example 6 A 5% solution ofA btestololaetone is prepared by dissolving 50 mg/ml. in benzyl benzoate and after autoclaving to sterilize, 0.25 ml. of the solution is injected I Example 7 15 mg. of A -testo-lolactone is dissolved in a solution comprised of 7.5 ml. of benzyl benzoate and 2.5 ml. of castor oil. The resultant solution is sterilized, then filled in vials of 5 ml. each and sterilized by autoclaving at 121 C. for 2 hours. The injectable solution may then be administered to the patient being treated.
This invention may be variously otherwise embodied Within the scope of the appended claims.
What is claimed is:
1. A parenterally administrable pharmaceutical composition compris-ing the acetophenonide of 16,17-dihydroxyprogesterone and a physiologically acceptable nontoxic pharmaceutical vehicle wherein at least by volume of said vehicle is benzyl benzoate.
2. A parenterally administrable pharmaceutical composition comprising testosterone palmitate and a physiologically acceptable non-toxis pharmaceutical vehicle wherein at least 75% by volume of said vehicle is benzyl benzoate.
3. A parenterally administrable pharmaceutical composition co-mprising testosterone enanthate and a physiologically acceptable non-toxic pharmaceutical vehicle wherein at least 75 by volume of said vehicle is benzyl benzoate.
4. A method of administering a large single dosage of a steroid which comprises parenterally administering to the patient being treated a composition comprising a steroid selected from the group consisting of 17-hydroxyprogesterone, the caproate ester of 17-hydroxyprogesterone, testosterone, the enanthate ester of testosterone, the palmitate ester of testosterone, estradiol, progesterone, and A -testololactone, and a pharmaceutical carrier, said carrier being at least 75% by volume of benzyl benzoate.
References Cited in the file of this patent Chemical Abstracts, vol. 52, p. 7620b, 1958 (abstr. of Gerosa et al., Ann. Chim., Rome, 47, pp. 1388-1393 (1957)).
Chemical Abstracts, vol. 42, p. 9084g, 1948.
Chemical Abstracts, vol. 47, p. 6611d, 1953.
Merck Index, 7th ed., 1960, p. 137.
U.S. Dispensatory, 25th ed., 1955, p. 160.
Sax: Handbook of Dangerous Materials, p. 45, Reinhold, New York, 1951. j

Claims (1)

  1. 4. A METHOD OF ADMINISTERING A LARGE SINGLE DOSAGE OF A STEROID WHICH COMPRISES PARENTERALLY ADMINISTERING TO THE PATIENT BEING TRETED A COMPOSITION COMPRISING A STEROID SELECTED FROM THE GROUP CONSISTING OF 17-HYDROXYPROGESTERONE, THE CAPROATE ESTER OF 17-HYDROXYPROGESTERONE, TESTOSTERONE, THE ENAANTHATE ESTER OF TESTOSTERONE, THE PLAMITATE ESTER OF TESTOSTERONE, ESTRADIOL, PROGESTERONE, AND $1-TESTOLALACTONE, AND A PHARMACEUTICAL CARRIER, SAID CARRIER BEING AT LEAST 75% BY VOLUME OF BENZYL BENZOATE.
US233931A 1962-10-29 1962-10-29 Injectable steroid compositions containing at least 75% benzyl benzoate Expired - Lifetime US3164520A (en)

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Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3538216A (en) * 1964-02-20 1970-11-03 Lab De Rech Physiques S A R L Injectable compositions of a drug suspended in an emulsion
US4016273A (en) * 1975-07-16 1977-04-05 American Cyanamid Company Sustained release forms of certain oxazepines for parenteral administration
US20030236236A1 (en) * 1999-06-30 2003-12-25 Feng-Jing Chen Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
US20050032762A1 (en) * 2003-03-14 2005-02-10 Doris Hubler Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
US20050043285A1 (en) * 2000-01-10 2005-02-24 Astrazeneca Ab Formulation
US20050152956A1 (en) * 2000-08-30 2005-07-14 Dudley Robert E. Method of increasing testosterone and related steroid concentrations in women
US20060003002A1 (en) * 2003-11-03 2006-01-05 Lipocine, Inc. Pharmaceutical compositions with synchronized solubilizer release
US20070014820A1 (en) * 2003-01-23 2007-01-18 Dana Litmanovitz Opioid formulations
US20070088012A1 (en) * 2005-04-08 2007-04-19 Woun Seo Method of treating or preventing type-2 diabetes
WO2006113505A3 (en) * 2005-04-15 2008-01-17 Clarus Therapeutics Inc Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same
US20090074859A1 (en) * 1999-11-23 2009-03-19 Mahesh Patel Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US20100173882A1 (en) * 2009-01-08 2010-07-08 Lipocine, Inc. Steroidal Compositions
US20110044519A1 (en) * 2008-03-13 2011-02-24 Levasseur Jr Donald P Multi-Function, Foot-Activated Controller for Imaging System
US20110142945A1 (en) * 2002-12-17 2011-06-16 Lipocine Inc. Hydrophobic Active Agent Compositions and Related Methods
US20110172196A1 (en) * 2000-08-30 2011-07-14 Dudley Robert E Pharmaceutical composition and method for treating hypogonadism
US8466137B2 (en) 2005-10-12 2013-06-18 Unimed Pharmaceuticals, Llc Testosterone gel and method of use
US8492369B2 (en) 2010-04-12 2013-07-23 Clarus Therapeutics Inc Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
JP2014521660A (en) * 2011-07-28 2014-08-28 リポカイン インコーポレーテッド Oral compositions containing 17-hydroxyprogesterone esters and related methods
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Cited By (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3538216A (en) * 1964-02-20 1970-11-03 Lab De Rech Physiques S A R L Injectable compositions of a drug suspended in an emulsion
US4016273A (en) * 1975-07-16 1977-04-05 American Cyanamid Company Sustained release forms of certain oxazepines for parenteral administration
US20100136105A1 (en) * 1999-06-30 2010-06-03 Lipocine, Inc. Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
US20030236236A1 (en) * 1999-06-30 2003-12-25 Feng-Jing Chen Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
US20100137271A1 (en) * 1999-06-30 2010-06-03 Lipocine, Inc. Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs
US20090074859A1 (en) * 1999-11-23 2009-03-19 Mahesh Patel Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US8329680B2 (en) 2000-01-10 2012-12-11 Astrazeneca Ab Formulation
US20050043285A1 (en) * 2000-01-10 2005-02-24 Astrazeneca Ab Formulation
US20100152149A1 (en) * 2000-01-10 2010-06-17 Evans John R Formulation
US8466139B2 (en) 2000-01-10 2013-06-18 Astrazeneca Ab Formulation
EP1250138B2 (en) † 2000-01-10 2015-07-08 AstraZeneca AB Fulvestrant formulation
US7456160B2 (en) 2000-01-10 2008-11-25 Astrazeneca Ab Formulation
EP2266573B1 (en) * 2000-01-10 2015-06-17 AstraZeneca AB Fulvestrant formulation
US20110201586A1 (en) * 2000-08-30 2011-08-18 Dudley Robert E Pharmaceutical composition and method for treating hypogonadism
US9125816B2 (en) 2000-08-30 2015-09-08 Besins Healthcare Inc. Pharmaceutical composition and method for treating hypogonadism
US9132089B2 (en) 2000-08-30 2015-09-15 Besins Healthcare Inc. Pharmaceutical composition and method for treating hypogonadism
US20110172196A1 (en) * 2000-08-30 2011-07-14 Dudley Robert E Pharmaceutical composition and method for treating hypogonadism
US20050152956A1 (en) * 2000-08-30 2005-07-14 Dudley Robert E. Method of increasing testosterone and related steroid concentrations in women
US20110142945A1 (en) * 2002-12-17 2011-06-16 Lipocine Inc. Hydrophobic Active Agent Compositions and Related Methods
US20070014820A1 (en) * 2003-01-23 2007-01-18 Dana Litmanovitz Opioid formulations
US7718640B2 (en) 2003-03-14 2010-05-18 Bayer-Schering Pharma Ag Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
US20090156564A1 (en) * 2003-03-14 2009-06-18 Doris Hubler Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
EP1743646A3 (en) * 2003-03-14 2007-03-28 Schering Aktiengesellschaft Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
HRP20050781B1 (en) * 2003-03-14 2015-04-10 Bayer Intellectual Property Gmbh METHODS AND PHARMACEUTICAL MIXTURES FOR RELIABLE ACHIEVEMENT OF ACCEPTABLE TESTOSTERONE LEVELS IN SERUM
US20050032762A1 (en) * 2003-03-14 2005-02-10 Doris Hubler Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
US8338395B2 (en) * 2003-03-14 2012-12-25 Bayer Intellectual Property Gmbh Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
NO335179B1 (en) * 2003-03-14 2014-10-13 Bayer Schering Pharma Ag Pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels, and use thereof
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