CA2243657C - Compositions for treatment of erectile dysfunction - Google Patents
Compositions for treatment of erectile dysfunction Download PDFInfo
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- CA2243657C CA2243657C CA002243657A CA2243657A CA2243657C CA 2243657 C CA2243657 C CA 2243657C CA 002243657 A CA002243657 A CA 002243657A CA 2243657 A CA2243657 A CA 2243657A CA 2243657 C CA2243657 C CA 2243657C
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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
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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
- A61K31/16—Amides, e.g. hydroxamic acids
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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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
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- 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
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- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
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- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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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
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
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Abstract
A carrier for use with vasoactive compounds for treatment of erectile dysfunction consists of a semi-solid gel at room temperatures while existing in a relatively liquid form at reduced temperatures. The carrier comprises a mixture of a lecithin compound, isopropyl palmitate, sorbic acid and pluronic gel comprised of pluronic and potassium sorbate in an aqueous base. A suitable local anaesthetic may be added to the carrier. A single-use applicator, comprising a syringe-type dispenser has a barrel which contains a pharmaceutically active dose of a vasoactive compound pre-mixed within a carrier as described above.
Description
COMPOSITIONS FOR TREATMENT OF ERECTILE DYSFUNCTION
FIELD OF THE INVENTION
The present invention relates to a novel carrier for use with vaso-active therapeutic compositions for the treatment of erectile dysfunction, or impotence, within human males, for delivery by catheter into the male urethra. In particular, the invention relates to an emulsified gel for carrying the vasodilator impotence treatment compounds such as alprostadil, with the gel existing as a semi-solid at room temperatures while being substantially liquid at refrigerated temperatures.
BACKGROUND OF THE INVENTION
Compositions for the treatment of impotence within human males include various compounds and compositions injected by catheter into the urethra. Typically, such 1 S compounds require injection prior to intercourse, and remain effective for a period of time.
Prior to the introduction of the compound alprostadil (commonly sold under the trademark "Caverject") and other like vasodilators, the primary treatment erectile dysfi~nction was the implantation of a penile prosthesis. Over the past decade, however, the introduction of intracavernous-injection therapy using vasoactive agents such as alprostadil have dramatically changed the treatment of impotence.
With several specific medical exceptions, alprostadil introduced by injection can result in high-quality erections in men whose impotence is caused by vascular, hormonal, neurologic, and psychogenic factors.
It has been found that interaction between the central nervous system and autonomic receptors in the arterial and corporeal (trabecular) smooth-muscle cells of the penis are the main cause of natural erections. Relaxation of arterial and trabecular smooth muscle tissue permits a increased inflow of blood into the sinusoidal spaces of the cavernous bodies and compression of the trabecular smooth muscle against the emissary veins. Alprostadil and other like compounds are vasoactive substances that compression of the trabecular smooth muscle against the emissary veins.
Alpro~tadil and other like compounds are vasoactive substances that inhibit sympathetic tone and directly relax the corporeal smooth muscle tissue, thus stimulating erectile functioning.
Specifically, alprostadil relaxes the smooth muscle of the corpus cavernosa.
Alprostadil is rapidly metabolized, thus minimizing its systemic effects.' The use of a vasodilator compound to treat erectile dysfunction by penile injection of the compound is disclosed in U.S. patent no. 4,127,118 (Latorre).
Intracavernous injection of alprostadil by application into the urethra is a well-accepted and e~cacious treatment for erectile dysfunction. Conveniently, such application is by way of a single-use syringe or other like delivery device. Other ways of administering alprostadil, such as by a medicated urethral system and in a topical gel; have not yet been demonstrated to have similar results. Although this formulation of alprostadil is now approved by the FDA and is easy to reconstitute in a single-use syringe, prescription of this medication is best left to urologists, who can offer the most comprehensive diagnostic evaluation and are best equipped to treat complications such as priapism. Simply prescribing an injection without conducting an appropriate 'evaluation does not constitute an appropriate standard of care. In the coming years, as the baby-boomer generation ages and looks for a quick fix for the diseases associated with aging, public awareness and its ease of administration will doubtless further popularize the use of intracavernous-injection therapy for erectile dysfunction.
Vasodilators such as alprostadil can be effectively delivered by way of direct urethral injection when they are emulsified within a gel. It has been found that an effective emulsion can be formed by formulating a composition from pluroruc and a lecithin-organo gel. This carrier preparation has the singular quality of being generally liquid at refrigerated temperatures and semi-solid at room temperatures. This permits the active 'The New England Journal of Medicine -- April 4, 1996 -- Volume 334, Number 14;
Larry I. Lipshultz, M.D.
FIELD OF THE INVENTION
The present invention relates to a novel carrier for use with vaso-active therapeutic compositions for the treatment of erectile dysfunction, or impotence, within human males, for delivery by catheter into the male urethra. In particular, the invention relates to an emulsified gel for carrying the vasodilator impotence treatment compounds such as alprostadil, with the gel existing as a semi-solid at room temperatures while being substantially liquid at refrigerated temperatures.
BACKGROUND OF THE INVENTION
Compositions for the treatment of impotence within human males include various compounds and compositions injected by catheter into the urethra. Typically, such 1 S compounds require injection prior to intercourse, and remain effective for a period of time.
Prior to the introduction of the compound alprostadil (commonly sold under the trademark "Caverject") and other like vasodilators, the primary treatment erectile dysfi~nction was the implantation of a penile prosthesis. Over the past decade, however, the introduction of intracavernous-injection therapy using vasoactive agents such as alprostadil have dramatically changed the treatment of impotence.
With several specific medical exceptions, alprostadil introduced by injection can result in high-quality erections in men whose impotence is caused by vascular, hormonal, neurologic, and psychogenic factors.
It has been found that interaction between the central nervous system and autonomic receptors in the arterial and corporeal (trabecular) smooth-muscle cells of the penis are the main cause of natural erections. Relaxation of arterial and trabecular smooth muscle tissue permits a increased inflow of blood into the sinusoidal spaces of the cavernous bodies and compression of the trabecular smooth muscle against the emissary veins. Alprostadil and other like compounds are vasoactive substances that compression of the trabecular smooth muscle against the emissary veins.
Alpro~tadil and other like compounds are vasoactive substances that inhibit sympathetic tone and directly relax the corporeal smooth muscle tissue, thus stimulating erectile functioning.
Specifically, alprostadil relaxes the smooth muscle of the corpus cavernosa.
Alprostadil is rapidly metabolized, thus minimizing its systemic effects.' The use of a vasodilator compound to treat erectile dysfunction by penile injection of the compound is disclosed in U.S. patent no. 4,127,118 (Latorre).
Intracavernous injection of alprostadil by application into the urethra is a well-accepted and e~cacious treatment for erectile dysfunction. Conveniently, such application is by way of a single-use syringe or other like delivery device. Other ways of administering alprostadil, such as by a medicated urethral system and in a topical gel; have not yet been demonstrated to have similar results. Although this formulation of alprostadil is now approved by the FDA and is easy to reconstitute in a single-use syringe, prescription of this medication is best left to urologists, who can offer the most comprehensive diagnostic evaluation and are best equipped to treat complications such as priapism. Simply prescribing an injection without conducting an appropriate 'evaluation does not constitute an appropriate standard of care. In the coming years, as the baby-boomer generation ages and looks for a quick fix for the diseases associated with aging, public awareness and its ease of administration will doubtless further popularize the use of intracavernous-injection therapy for erectile dysfunction.
Vasodilators such as alprostadil can be effectively delivered by way of direct urethral injection when they are emulsified within a gel. It has been found that an effective emulsion can be formed by formulating a composition from pluroruc and a lecithin-organo gel. This carrier preparation has the singular quality of being generally liquid at refrigerated temperatures and semi-solid at room temperatures. This permits the active 'The New England Journal of Medicine -- April 4, 1996 -- Volume 334, Number 14;
Larry I. Lipshultz, M.D.
ingredient to be mixed into the carrier at reduced temperatures to prevent denaturing, and further permits the resulting therapeutic compound to be easily introduced into a syringe or other like delivery device. The preparation may then be easily transported and stored at room temperatures as a semi-solid within the delivery device with minimal risk of leakage.
The resulting preparation may then be delivered by injection with a catheter-tipped syringe into the urethra, typically by insertion of the catheter about one inch into the urethra.
The use of a pluronic/lecithin type gel has been previously disclosed for use in treatment of blood vessel disorders of the skin and subcutaneous tissues (U.S. Patent 5,510,391 -Elson). However, it has not been previously suggested to deliver vasoactive 'substances for the treatment of male impotence in a gel of this type.
It is desirable to provide a preparation comprising an active impotence treatment compound with a carrier, whereby the preparation may be stored in a semi-solid gel form.
This permits the preparation to be stored in single-use syringes, without risk of leakage or spillage. This aspect is particularly important in this type of preparation, since typically users will carry with them a single-use syringe applicators on their person, or have the applicators conveniently stored in a bedroom or the like. It is particularly important to avoid inadvertent spillage or leakage in such circumstances. Accordingly, it is useful to provide the pharmaceutically active compound in a delivery system that includes a gel-type carrier that is semi-solid at room temperatures.
It is a further requirement that such a carrier be sufficiently fluid to permit delivery through a generally conventional syringe and catheter combination. Further, the carrier must be sufl-iciently fluid to permit the preparation of a mixture of the active ingredient and the carrier, without the necessity of heating the carrier, which may deactivate the active ingredient. Accordingly, it is desirable to provide a carrier that may be liquefied or partly liquefied at a decreased temperature.
Alprostadil and similar compounds are in their normal state relatively hydrophilic.
The resulting preparation may then be delivered by injection with a catheter-tipped syringe into the urethra, typically by insertion of the catheter about one inch into the urethra.
The use of a pluronic/lecithin type gel has been previously disclosed for use in treatment of blood vessel disorders of the skin and subcutaneous tissues (U.S. Patent 5,510,391 -Elson). However, it has not been previously suggested to deliver vasoactive 'substances for the treatment of male impotence in a gel of this type.
It is desirable to provide a preparation comprising an active impotence treatment compound with a carrier, whereby the preparation may be stored in a semi-solid gel form.
This permits the preparation to be stored in single-use syringes, without risk of leakage or spillage. This aspect is particularly important in this type of preparation, since typically users will carry with them a single-use syringe applicators on their person, or have the applicators conveniently stored in a bedroom or the like. It is particularly important to avoid inadvertent spillage or leakage in such circumstances. Accordingly, it is useful to provide the pharmaceutically active compound in a delivery system that includes a gel-type carrier that is semi-solid at room temperatures.
It is a further requirement that such a carrier be sufficiently fluid to permit delivery through a generally conventional syringe and catheter combination. Further, the carrier must be sufl-iciently fluid to permit the preparation of a mixture of the active ingredient and the carrier, without the necessity of heating the carrier, which may deactivate the active ingredient. Accordingly, it is desirable to provide a carrier that may be liquefied or partly liquefied at a decreased temperature.
Alprostadil and similar compounds are in their normal state relatively hydrophilic.
Accordingly, passage across liposoluble cell membranes may be hindered and this can delay the activity of the compound. The use of a lecithin-based gel Garner as in the present invention renders the mixture relatively lipid soluble and assists passage of the compound across cell membranes.
In a further aspect, it is desirable to provide a local anaesthetic such as lidocain within the carrier to facilitate use of the medicament.
SUMMARY OF THE INVENTION
It is an object of the invention to provide an improved delivery means for vasoactive compounds for treatment of erectile dysfunction. It is a further specific object to provide a semi-solid gel-type combination of a carrier and a therapeutically active substance of the group that includes alprostadil and other vasoactive compounds, for delivery by way of a catheter-tipped syringe into the human male urethra. It is a further object to provide a delivery system for delivery of a vasodilator for treatment of impotence, comprising a syringe containing a single dose of a vasoactive compound carried within an emulsion that permits an effective delivery of the medication. It is a further object to provide a carrier/active ingredient combination that may be retained at room temperature (i. e. 16 - 28 ° C
approximately) within a syringe or other like holder as a semi-solid gel without substantial risk of spillage or leakage, but which is sufficiently liquid at refrigerated temperatures (i.e.
about 0 -10°C) to permit a pharmacist to fil individual syringes with the mixture.
In light of the foregoing objects, the present invention comprises in one aspect a composition comprising a carrier for a pharmaceutically active vasoactive preparation for the treatment of male erectile dysfunction. The carrier comprises a mixture of a lecithin compound, isopropyl palmitate, sorbic acid and Pluronic ~ gel comprised of Pluronic and potassium sorbate in an aqueous base, in a proportion such that the Garner has the quality of existing in a semi-solid gel state at room temperature and in a relatively liquid state at temperatures of between about 0 and 10° C.
The term "Pluronic" is a proprietary name for difucntional block polymers terminating in primary hydroxyl groups. In particular, such compounds are polyoxyalkylene derivatives of propylene glycol (The Condensed Chemical Dictionary, 7°' ed. 1966).
Preferably, the vasoactive compound comprises alprostadil.
The lecithin organic gel preferably comprises a mixture of lecithin soya granules;
isopropyl palmitate and sorbic acid.
In a further aspect, the carrier includes a suitable local anaesthetic, such as a 2%
lidocain solution.
In a further aspect, the invention comprises a method of preparing a Garner for a vasoactive pharmaceutical preparation such as alprostadil, comprising the steps of preparing a stock pluronic solution by combining and dissolving pluronic and potassium sorbate within water chilled to approximately between about 0 and 10° C;
mixing together a lecithin compound, isopropyl palmitate, sorbic acid and permitting said mixture to stand until a syrupy consistency is achieved;
combining the mixture with said stock solution at a temperature of between about 0 and 10° C;
the ratio of the compounds within the Garner being selected to achieve a carrier having a semi-solid gel consistency at room temperature and a relatively liquid consistence at temperatures between about 0 and 10° C.
The invention comprises in another aspect the use of a therapeutically effective concentration of a vasoactive medicament such as alprostadil carned within a gel of the type described above for the treatment of male erectile dysfunction.
In another aspect, the invention comprises a delivery means for delivering a dose of a preparation as described above. The delivery means comprises a single-use applicator, comprising a syringe-type dispenser, the barrel of which contains a pharmaceutically active dose of a vasoactive compound pre-mixed within a carrier as described above.
- 5 (a) -Having thus characterised and summarized the invention, the invention will now be described in detail by way of a description of a preferred embodiment thereof.
In a further aspect, it is desirable to provide a local anaesthetic such as lidocain within the carrier to facilitate use of the medicament.
SUMMARY OF THE INVENTION
It is an object of the invention to provide an improved delivery means for vasoactive compounds for treatment of erectile dysfunction. It is a further specific object to provide a semi-solid gel-type combination of a carrier and a therapeutically active substance of the group that includes alprostadil and other vasoactive compounds, for delivery by way of a catheter-tipped syringe into the human male urethra. It is a further object to provide a delivery system for delivery of a vasodilator for treatment of impotence, comprising a syringe containing a single dose of a vasoactive compound carried within an emulsion that permits an effective delivery of the medication. It is a further object to provide a carrier/active ingredient combination that may be retained at room temperature (i. e. 16 - 28 ° C
approximately) within a syringe or other like holder as a semi-solid gel without substantial risk of spillage or leakage, but which is sufficiently liquid at refrigerated temperatures (i.e.
about 0 -10°C) to permit a pharmacist to fil individual syringes with the mixture.
In light of the foregoing objects, the present invention comprises in one aspect a composition comprising a carrier for a pharmaceutically active vasoactive preparation for the treatment of male erectile dysfunction. The carrier comprises a mixture of a lecithin compound, isopropyl palmitate, sorbic acid and Pluronic ~ gel comprised of Pluronic and potassium sorbate in an aqueous base, in a proportion such that the Garner has the quality of existing in a semi-solid gel state at room temperature and in a relatively liquid state at temperatures of between about 0 and 10° C.
The term "Pluronic" is a proprietary name for difucntional block polymers terminating in primary hydroxyl groups. In particular, such compounds are polyoxyalkylene derivatives of propylene glycol (The Condensed Chemical Dictionary, 7°' ed. 1966).
Preferably, the vasoactive compound comprises alprostadil.
The lecithin organic gel preferably comprises a mixture of lecithin soya granules;
isopropyl palmitate and sorbic acid.
In a further aspect, the carrier includes a suitable local anaesthetic, such as a 2%
lidocain solution.
In a further aspect, the invention comprises a method of preparing a Garner for a vasoactive pharmaceutical preparation such as alprostadil, comprising the steps of preparing a stock pluronic solution by combining and dissolving pluronic and potassium sorbate within water chilled to approximately between about 0 and 10° C;
mixing together a lecithin compound, isopropyl palmitate, sorbic acid and permitting said mixture to stand until a syrupy consistency is achieved;
combining the mixture with said stock solution at a temperature of between about 0 and 10° C;
the ratio of the compounds within the Garner being selected to achieve a carrier having a semi-solid gel consistency at room temperature and a relatively liquid consistence at temperatures between about 0 and 10° C.
The invention comprises in another aspect the use of a therapeutically effective concentration of a vasoactive medicament such as alprostadil carned within a gel of the type described above for the treatment of male erectile dysfunction.
In another aspect, the invention comprises a delivery means for delivering a dose of a preparation as described above. The delivery means comprises a single-use applicator, comprising a syringe-type dispenser, the barrel of which contains a pharmaceutically active dose of a vasoactive compound pre-mixed within a carrier as described above.
- 5 (a) -Having thus characterised and summarized the invention, the invention will now be described in detail by way of a description of a preferred embodiment thereof.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
' The preferred present invention comprises a single dosage application of an active ingredient, namely alprostadil or other like vasoactive compound for treatment of male erectile dysfunction, suspended within a pluronic.gel. The dosage is contained within a catheter-tipped syringe. A typical dosage is about 0.1-0.2 cc.
The pluronic gel carrier according to the present invention comprises a mixture of lecithin soya granules, isopropyl palmitate SF, sorbic acid and pluronic gel in an aqueous base.
The mixture is prepared with ratios of the ingredients sufficient to provide a semi-solid gel at room temperatures, while being substantially liquid at refrigerated temperatures.
In one example, the mixture is prepared by combining these compounds in the following amounts:
Lecithin soya granules 10 gm Isopropyl Palmitate SF 10 gm (11.7 ml.) Sorbic acid NF-FCC powder 0.3 gm Pluronic gel 20% q.s. 100 ml The stock solution of pluronic gel 20% comprises the following mixture:
Pluronic F127 NF 20 gm Potassium Sorbate NF 0.3 gm Purified Water q.s.
Potassium sorbate and pluronic is combined and chilled (0-10° C) and purified water is added to bring the volume to 100 ml, following which the mixture is stirred or mixed for 12-24 hours, with additional water added as required to bring the final volume to 100 ml.
The resulting gel is refrigerated, and dissolution into a relatively liquid form occurs upon chilling. To compensate for volume reduction upon chilling, additional water is added as required to bring the volume back to 100 ml. The stock solution of pluronic gel is maintained at a refrigerated temperature (i.e. 0-10° C) until used, to prevent solidification.
The lecithin/pluronic mixture is prepared by dispersing the lecithin granules and the sorbic acid in isopropyl palmitate, and permitting this mixture to stand about 8-16 hours. A
mixture of syrupy consistency will result. The chilled pluronic gel stock solution is mixed into to the resulting mixture to bring the total volume to 100 ml.
The resulting gel comprises a carrier for an active ingredient, preferably alprostadil, which is added in therapeutic amounts. Conveniently, a single dosage is 0.1-0.2 ml.
of the carrier/active ingredient combination. Typically, a therapeutic dosage of alprostadil gel is about 500-1000 mcg. Accordingly, either sufficient active ingredient may be added to the entire carrier batch to achieve the desired carrier/pharmaceutical mixture, or individual dosages of the therapeutically active preparation may as desired be prepared.
A pharmaceutically active dosage of a local anaesthetic may be added to the mixture. For example, sufficient lidocain may be added such that the final mixture comprises a 2%
lidocain solution.
Upon preparation of the therapeutically active carrier/active ingredient preparation, one or more single use syringes are filled with a selected single dose amount of the preparation.
Typically, the filled syringes will be prepared by a pharmacist and the exact dosage will be determined by the patient's physician. The syringes may be easily filled while the mixture is chilled, since at these temperatures the mixture remains in a generally liquid state. The preparation solidifies into a semi-solid gel upon reaching room temperature, and may be stored in this form without substantial risk of leakage or spillage.
The resulting compound will gel into a semi-solid upon reaching room temperature:
Within this state, the compound will in normal circumstances not leak or spill from a syringe or other like delivery device. However, the mixture will remain sufficiently fluid to permit the user to, discharge the mixture through the catheter tip of the syringe.
' The preferred present invention comprises a single dosage application of an active ingredient, namely alprostadil or other like vasoactive compound for treatment of male erectile dysfunction, suspended within a pluronic.gel. The dosage is contained within a catheter-tipped syringe. A typical dosage is about 0.1-0.2 cc.
The pluronic gel carrier according to the present invention comprises a mixture of lecithin soya granules, isopropyl palmitate SF, sorbic acid and pluronic gel in an aqueous base.
The mixture is prepared with ratios of the ingredients sufficient to provide a semi-solid gel at room temperatures, while being substantially liquid at refrigerated temperatures.
In one example, the mixture is prepared by combining these compounds in the following amounts:
Lecithin soya granules 10 gm Isopropyl Palmitate SF 10 gm (11.7 ml.) Sorbic acid NF-FCC powder 0.3 gm Pluronic gel 20% q.s. 100 ml The stock solution of pluronic gel 20% comprises the following mixture:
Pluronic F127 NF 20 gm Potassium Sorbate NF 0.3 gm Purified Water q.s.
Potassium sorbate and pluronic is combined and chilled (0-10° C) and purified water is added to bring the volume to 100 ml, following which the mixture is stirred or mixed for 12-24 hours, with additional water added as required to bring the final volume to 100 ml.
The resulting gel is refrigerated, and dissolution into a relatively liquid form occurs upon chilling. To compensate for volume reduction upon chilling, additional water is added as required to bring the volume back to 100 ml. The stock solution of pluronic gel is maintained at a refrigerated temperature (i.e. 0-10° C) until used, to prevent solidification.
The lecithin/pluronic mixture is prepared by dispersing the lecithin granules and the sorbic acid in isopropyl palmitate, and permitting this mixture to stand about 8-16 hours. A
mixture of syrupy consistency will result. The chilled pluronic gel stock solution is mixed into to the resulting mixture to bring the total volume to 100 ml.
The resulting gel comprises a carrier for an active ingredient, preferably alprostadil, which is added in therapeutic amounts. Conveniently, a single dosage is 0.1-0.2 ml.
of the carrier/active ingredient combination. Typically, a therapeutic dosage of alprostadil gel is about 500-1000 mcg. Accordingly, either sufficient active ingredient may be added to the entire carrier batch to achieve the desired carrier/pharmaceutical mixture, or individual dosages of the therapeutically active preparation may as desired be prepared.
A pharmaceutically active dosage of a local anaesthetic may be added to the mixture. For example, sufficient lidocain may be added such that the final mixture comprises a 2%
lidocain solution.
Upon preparation of the therapeutically active carrier/active ingredient preparation, one or more single use syringes are filled with a selected single dose amount of the preparation.
Typically, the filled syringes will be prepared by a pharmacist and the exact dosage will be determined by the patient's physician. The syringes may be easily filled while the mixture is chilled, since at these temperatures the mixture remains in a generally liquid state. The preparation solidifies into a semi-solid gel upon reaching room temperature, and may be stored in this form without substantial risk of leakage or spillage.
The resulting compound will gel into a semi-solid upon reaching room temperature:
Within this state, the compound will in normal circumstances not leak or spill from a syringe or other like delivery device. However, the mixture will remain sufficiently fluid to permit the user to, discharge the mixture through the catheter tip of the syringe.
The invention further comprises the combination of a syringe or other like delivery apparatus, with the above-described mixture contained within the syringe barrel. It will be seen that any known delivery apparatus may be adapted for use with the present invention, the apparatus being provided with a barrel or other chamber for holding a therapeutic dose of the mixture, in communication with a catheter or like delivery tube for insertion into the urethra.
It will also be seen that the carrier described above may be used in association with other pharmaceutical preparations having similar requirements as described above.
However, the Garner is particularly suited for use with vasoactive impotence treatment preparations.
It will be seen that although the present invention has been described by way of a preferred embodiment thereof, numerous variations of and departures from this version may be made without departing from the spirit and scope of the invention, as described in the appended claims. In a further aspect, it may be noted that while precise amounts and concentrations of various components of the invention are described in this specification, persons skilled in the art will recognize that the present invention may be still achieved even if at least some of these quantities and ratios are varied.
It will also be seen that the carrier described above may be used in association with other pharmaceutical preparations having similar requirements as described above.
However, the Garner is particularly suited for use with vasoactive impotence treatment preparations.
It will be seen that although the present invention has been described by way of a preferred embodiment thereof, numerous variations of and departures from this version may be made without departing from the spirit and scope of the invention, as described in the appended claims. In a further aspect, it may be noted that while precise amounts and concentrations of various components of the invention are described in this specification, persons skilled in the art will recognize that the present invention may be still achieved even if at least some of these quantities and ratios are varied.
Claims (24)
1. A carrier for a pharmaceutical preparation for the treatment of male erectile dysfunction, said preparation comprising a vasoactive substance, said carrier comprising a mixture of a lecithin compound, isopropyl palmitate, sorbic acid and a gel comprising a polyoxyalkylene derivative of propylene glycol and potassium sorbate in an aqueous base, in a proportion such that said mixture has the quality of existing in a semi-solid gel state at room temperature and in a relatively liquid state at temperatures of between 0 and 10°C.
2. A earner as in claim 1, wherein said gel comprises approximately 20% by weight of said polyoxyalkylene derivative of propylene glycol and 0.3% by weight potassium sorbate.
3. A carrier as in claim 1, wherein said mixture comprises approximately 10%
by weight lecithin, 10% by weight isopropyl palmitate and 0.3% by weight sorbic acid.
by weight lecithin, 10% by weight isopropyl palmitate and 0.3% by weight sorbic acid.
4. A carrier as in claim 1, wherein said lecithin compound comprises lecithin soya granules.
5. A carrier as in claim 1, further comprising a local anaesthetic in a therapeutically effective concentration.
6. A carrier as in claim 5, wherein said anaesthetic comprises lidocain.
7. A pharmaceutically active preparation comprising a carrier and a therapeutically effective concentration of a vasoactive medicament for the treatment of male erectile dysfunction, said carrier comprising a mixture of a lecithin compound, isopropyl palmitate, sorbic acid and a gel comprised of a polyoxyalkylene derivative of propylene glycol and potassium sorbate in an aqueous base, in a proportion such that said carrier has the quality of existing in a semi-solid gel state at room temperature and in a relatively liquid state at temperatures of between about 0 and 10° C.
8. A preparation as in claim 7, wherein said gel comprises approximately 20%
by weight of said propylene glycol derivative and 0.3% by weight potassium sorbate.
by weight of said propylene glycol derivative and 0.3% by weight potassium sorbate.
9. A preparation as in claim 7, wherein said mixture comprises approximately
10% by weight lecithin, 10% by weight isopropyl palmitate and 0.3% by weight sorbic acid.
10. A preparation as in claim 7, wherein said vasoactive compound comprises alprostadil.
10. A preparation as in claim 7, wherein said vasoactive compound comprises alprostadil.
11. A preparation as in claim 7, wherein said lecithin compound comprises lecithin soya granules.
12. A preparation as in claim 7, further comprising a local anaesthetic in a therapeutically effective concentration.
13. A preparation as in claim 12, wherein said anaesthetic comprises lidocain.
14. A method for preparing a carrier for a medicament for the treatment of male erectile dysfunction, said medicament comprising a therapeutically effective vasoactive pharmaceutical preparation, comprising the steps of:
preparing a stock solution by combining and dissolving a polyoxyalkylene derivative of propylene glycol and potassium sorbate within water chilled to approximately between about 0 and 10° C;
mixing together a lecithin compound, isopropyl palmitate, sorbic acid and permitting said mixture to stand until a syrupy consistency is achieved;
combining said mixture with said stock solution at a temperature of between about 0 and 10° C;
the quantities of said compounds within said carrier being selected to achieve a carrier having a semi-solid gel consistency at room temperature and a relatively liquid consistence at temperatures between 0 and 10° C.
preparing a stock solution by combining and dissolving a polyoxyalkylene derivative of propylene glycol and potassium sorbate within water chilled to approximately between about 0 and 10° C;
mixing together a lecithin compound, isopropyl palmitate, sorbic acid and permitting said mixture to stand until a syrupy consistency is achieved;
combining said mixture with said stock solution at a temperature of between about 0 and 10° C;
the quantities of said compounds within said carrier being selected to achieve a carrier having a semi-solid gel consistency at room temperature and a relatively liquid consistence at temperatures between 0 and 10° C.
15. A method as in claim 14, wherein said stock solution comprises approximately 20% by weight of said propylene glycol derivative and 0.3% by weight potassium sorbate.
16. A method as in claim 14, wherein said mixture comprises approximately 10%
by weight lecithin, 10% by weight isopropyl palmitate and 0.3% by weight sorbic acid.
by weight lecithin, 10% by weight isopropyl palmitate and 0.3% by weight sorbic acid.
17. A method as in claim 14, wherein said lecithin comprises granular soya lecithin.
18. A delivery means for delivering a pharmaceutically active preparation comprising a syringe containing a carrier and a therapeutically effective dose of a vasoactive medicament for the treatment of male erectile dysfunction, said carrier comprising a mixture of a lecithin compound, isopropyl palmitate, sorbic acid and a gel comprised of a polyoxyalkylene derivative of propylene glycol and potassium sorbate in an aqueous base, said mixture having the quality of existing in a semi-solid gel state at room temperature and in a relatively liquid state at temperatures of between about 0 and 10° C.
19. A delivery means as in claim 18, wherein said gel comprises approximately
20% by weight of said propylene glycol derivative and 0.3% by weight potassium sorbate.
20. A delivery means as in claim 18, wherein said mixture comprises approximately 10% by weight lecithin, 10% by weight isopropyl palmitate and 0.3%
by weight sorbic acid.
20. A delivery means as in claim 18, wherein said mixture comprises approximately 10% by weight lecithin, 10% by weight isopropyl palmitate and 0.3%
by weight sorbic acid.
21. A delivery means as in claim 18, wherein said vasoactive compound comprises alprostadil.
22. A delivery means as in claim 18, wherein said lecithin compound comprises lecithin soya granules.
23. A delivery means as in claim 18, further comprising a local anaesthetic carried by said carrier in a therapeutically effective concentration.
24. A delivery means as in claim 23, wherein said anaesthetic comprises lidocain.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002243657A CA2243657C (en) | 1998-07-21 | 1998-07-21 | Compositions for treatment of erectile dysfunction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002243657A CA2243657C (en) | 1998-07-21 | 1998-07-21 | Compositions for treatment of erectile dysfunction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2243657A1 CA2243657A1 (en) | 2000-01-21 |
| CA2243657C true CA2243657C (en) | 2003-03-25 |
Family
ID=4162675
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002243657A Expired - Lifetime CA2243657C (en) | 1998-07-21 | 1998-07-21 | Compositions for treatment of erectile dysfunction |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2243657C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3266458A1 (en) * | 2016-07-05 | 2018-01-10 | Fagron B.V. | Method and composition and kit for treating erectile dysfunction |
-
1998
- 1998-07-21 CA CA002243657A patent/CA2243657C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2243657A1 (en) | 2000-01-21 |
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