CN102188375A - Delivery system - Google Patents
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- CN102188375A CN102188375A CN2011101190673A CN201110119067A CN102188375A CN 102188375 A CN102188375 A CN 102188375A CN 2011101190673 A CN2011101190673 A CN 2011101190673A CN 201110119067 A CN201110119067 A CN 201110119067A CN 102188375 A CN102188375 A CN 102188375A
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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
- A61K9/10—Dispersions; Emulsions
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/42—Gynaecological or obstetrical instruments or methods
- A61B2017/4216—Operations on uterus, e.g. endometrium
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- Heart & Thoracic Surgery (AREA)
- Gynecology & Obstetrics (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Dispersion Chemistry (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
Abstract
The invention relates to a delivery system. Concretely, a pharmaceutical delivery system that releases an active agent in a controlled manner for an extended period in the vaginal cavity to treat or cure ailments associated with the vaginal cavity or proximal areas. The delivery system includes an applicator which is composed of a high internal phase emulsion, allowing the delivery system to adhere to the mueosal surfaces of the body, primarily the lining of vaginal cavity. The delivery system can maintain the high internal phase emulsion at a temperature of 86 DEG F for at least one month, without decomposition or instability of the emulsion.
Description
The application is that application number is 200580000243.4, the applying date is on July 8th, 2005, denomination of invention is divided an application for the patent application of " delivery system ".
Technical field
The present invention relates to a kind of drug delivery system that comprises applicator, it shows the controlled release of activating agent, and this delivery system has high inner phase and compares outward, and it is suitable for using in vaginal canal.
Background technology
Be used to prevent, control, the Drug therapy of the female reproductive system of diagnosis and cure diseases generally includes forms of pharmacologically active agents is delivered to vaginal canal and adjacent organs.Usually, activating agent is made form or other form well known in the art of gel, foam, emulsifiable paste, suppository, solution tablet.Yet these delivery form do not show with activating agent in a controlled manner, especially are delivered to vaginal canal in three hours or longer time, and the ability of high-caliber bioadhesion and the high level stability under high temperature or low temperature environment is provided simultaneously.
The biological characteristics of vagina and adjacent domain makes treatment and bioactive agent delivery delivered to the vaginal canal difficulty.For example, vaginal canal shows aqueous environment, and wherein the pH of liquid is 4.5-5.5, and internal temperature is about 98.6 °F (37 ℃).The environment of vaginal canal also helps microorganism, as antibacterial and fungus, comprises zymic growth, and foreign particle, and Tathagata is from the seminal fluid of sexual intercourse and retaining of menstruation residue.The characteristics of vaginal canal are significant physical deformation abilities, as sexual intercourse or insert physical deformation due to the tampon.
Be generally used for treating disease in the vaginal canal with uncomfortable such as the activating agent of antifungal.Yet the pharmacy of these activating agents and chemism all do not reach the optimal level of effectiveness.The reason of this restriction of effectiveness partly or entirely is because the defective of existing delivery system causes.In fact, existing delivery system was not presented at three hours or discharged forms of pharmacologically active agents in safest mode in longer time, and did not cause the ability of the problem relevant with bioadhesion or the excessive release of active pharmaceutical ingredient.For example, after inserting vaginal canal, existing delivery system generally almost begins dissolving immediately, disperses or liquefaction.Therefore, these delivery systems usually to the bioadhesion of vaginal wall seldom.
Conventional delivery system contains a large amount of propylene glycol in preparation, it is in order to increase the availability of the medicine that is mixed.Active pharmaceutical compounds is at solvent sample molecule, and the biomembranous penetration capacity that penetrates of the increase that provides as the possible dissolving in the propylene glycol and by propylene glycol is favourable.This deduction that is used for the delivery system of mucosa may be by exaggerative, in the time of particularly in being used for vaginal canal.The moisture character of environment provides the optimal conditions for the whole body absorption of dissolved active pharmaceutical compounds.The chemical compound that comprises the dissolving forms of pharmacologically active agents of high concentration can increase the whole body absorbability of this activating agent.Although this is a desired effects in some cases, in the treatment local mucous membrane infects, removes beneficial drug possibility extended treatment state, and in some cases, may cause the whole body of active pharmaceutical compounds to absorb the disadvantageous level that reaches from adjacent domain.
In addition, the delivery system that is subjected to comprising an amount of infringement to excessive propylene glycol may have some physical property.For conventional Emulsion, an amount of extremely excessive propylene glycol can increase dissolving and the liquefaction of this delivery system in the vaginal canal hydrophilic environment.For unique more emulsion systems, the propylene glycol that comprises higher concentration can cause the physical instability under room temperature and the high temperature.
Therefore, the Emulsion of conventional and unique delivery system can not provide optimum vaginal canal internal therapy.Demand to controlled release delivery system that vagina and uncomfortable optimum treatment are provided in this area is not met.Therefore, existence is to the demand that is not met of following delivery system, and described delivery system provides the continuous release of pharmaceutically active agents to vaginal canal, particularly this system in long-time, in at least three hours, provide pharmaceutical active, and high bioadhesion level is provided.And then, exist in the art reducing the demand that is not met of the delivery system of propylene glycol ratio in the preparation.
Summary of the invention
The present invention by provide a kind of be used for vaginal canal overcome the problems referred to above and other problem than the more effective delivery system of existing delivery system.Particularly, first embodiment of the present invention provides a kind of delivery system for the treatment of the woman's vaginal cavity fungal infection, it comprises imdazole derivatives activating agent and one or more pharmaceutically acceptable excipient of effective dose, it makes this activating agent be released into the site in the vaginal canal in a controlled manner, and wherein this delivery system is inner phase and the emulsion of comparing outward greater than 70%.Second embodiment of the present invention is a kind of method for the treatment of the vagina fungal infection, described method comprises and gives vaginal canal with a kind of delivery system, described delivery system contains the imdazole derivatives activating agent of effective dose and one or more makes this activating agent be released into the pharmaceutically acceptable excipient in the site in the vaginal canal in a controlled manner, and wherein this delivery system is inner phase and the emulsion of comparing outward greater than 70%.
More particularly, this delivery system comprises compactness, prefill, the i.e. applicator of usefulness that is used for to body chamber administered medicaments, and described applicator has long and narrow body, and it has near-end to bestow end and far-end prehension end.Body has enough length with the desired site administered medicaments in selected body chamber.The proximal part of long and narrow body forms reservoir, and it is suitable for holding the medicine of scheduled volume.The distal portions of long and narrow body forms piston chamber.Locking device is positioned at the end of bestowing of this reservoir, and propulsion plant is positioned at its far-end, the junction in reservoir and piston accessory chamber.Telescopic piston rod accessory have be attached thereto in order to limit scalable prolongation and to prevent the scalable destructive stopping means of piston rod accessory, telescopic piston rod accessory links to each other with propulsion plant.Grip device is used to operate described telescopic piston rod accessory.The following operation of this applicator: hold its prehension end, and make the closing end pro-and be inserted into the expectation the chamber in.By grip device the piston accessory is withdrawn into the border of stopping means, then piston accessory near-end ground for this long and narrow body is passed, thereby produced pressure, the open closed assembly is also bestowed medicine in reservoir.
With reference to accompanying drawing, other characteristics of the present invention will become clear.Hereinafter or by after putting into practice the present invention and learning, it is more clear that other advantage of the present invention and new feature also will become to those skilled in the art by research.
Description of drawings
In the accompanying drawings,
Fig. 1 is the side view of applicator of explanation principle of the present invention, with compactness, promptly use position display;
Fig. 2 is the exploded view of the applicator of Fig. 1, shows enclosure portion, cylinder part, first piston assembly, second piston component (forming the piston accessory together), and gripper.
The specific embodiment
As depicted in figs. 1 and 2, applicator 20 has and bestows end 22 and prehension end 24.Cylindricality assembly 26 has medicament reservoir part, piston accessory chamber part as the main body of this applicator, and grasping surface part 32.Closed component 34 closes at the outer radius portion of dwindling 36 of cylindricality assembly 26 slidably.Piston accessory 38 has the first piston assembly 40 that has piston portion 42, and second piston component 44, and piston accessory 38 closes in the cylindricality assembly 26 slidably; Piston portion 42 is positioned at medicament reservoir part 28, and the remainder of piston accessory 38 is positioned at piston accessory chamber part 30.Gripper 46 provides for second piston element 44.
The invention provides a kind of delivery system, it provides the high inner phase and the emulsion of comparing of a kind of 70%-90% of having outward, and preferably, non-lipid wherein accounts for about 70 volume %-90 volume % of this system mutually.Compare with prior art formulations, preparation of the present invention has reduced preferred about 20% to about 80% with the amount of propylene glycol from commercially available bioadhesion system, and more preferably from about 25%, and still keep the same high internal phase emulsions ratio of 70%-90%.
In addition, the present invention can keep at least one month under 86 temperature, be preferably greater than one month, more preferably greater than two months, and more preferably greater than half a year, more preferably greater than 1 year, for example three to five years.Stability increases makes the present invention can be stored in the environment that easily is affected by climate change or in the extreme temperature environment.This improvement is commonly referred to " storage life improvement ".
The invention provides a kind of delivery system that is used for vaginal canal, wherein this delivery system is sent forms of pharmacologically active agents to vaginal canal in a controlled manner in long-time.In a variant of the present invention, be at least 3 hours for a long time, in most of the cases, the time can continue 10 days or longer.The feature of this delivery system is the High Internal Phase Emulsion ratio.The emulsion that this delivery system preferably is made up of the hydrophilic component that accounts for the 70 volume % of this system.
This delivery system provides reparation and maintaining healthy vaginal environment and cures disease or the uncomfortable activating agent that influences vaginal canal." vaginal canal " also comprises adjacent domain, and for example, it comprises vagina, female urethra, as the organ and the tissue of urethral orifice, vaginal canal opening part, and by the accessible genitals in this chamber.The feature of this delivery system also is to adhere to (being also referred to as " bioadhesion ") to vaginal canal wall and adjacent domain, comprises the ability of epithelial cell, tissue and organ.
This delivery system is release bioactive agent not only, and its also in a controlled manner release bioactive agent to obtain optimum absorption.Therefore, this activating agent can be absorbed in absorption or action site, performance pharmacology or other effect present in an amount at least sufficient to cause the reaction of the expectation consistent with the intrinsic property of this activating agent, and in the time of expectation this reaction are maintained proper level.Delivery system preferable feature of the present invention is that the activating agent controlled release is to acceptor site, action site, absorption site or use the site, and realizes the effect of expectation in this site.This delivery system is unmixing in water preferably, and uses harmless in vaginal canal.
Delivery system of the present invention can comprise the combination of active and nonactive ingredient (being also referred to as " excipient " herein).Non-active ingredient for example, is used for dissolving, suspension, multiviscosisty, dilution, emulsifying, stabilisation, anticorrosion, protection, painted, flavoring and adjustment active component, makes it become safe in utilization, convenient or uses acceptable available and effective preparation.Active component for example, can account for the 1.0%-10% of this delivery system total weight percent, preferably accounts for about 1.5%-2.5%, more preferably accounts for approximately 2.0%, and the medicine or the chemotherapy of vaginal canal are provided.Thereby preparing these active component discharges in a controlled manner.The active component that comprises activating agent can be any approval or the composition that is used for the treatment of, prevents, cures or alleviate any disease of vaginal canal.The main active of delivery system of the present invention is an imdazole derivatives, and they are natural antifungal and antibacterial.Imdazole derivatives can be the form of pharmaceutically acceptable salt such as nitrate.The example that can be used for imdazole derivatives of the present invention comprises miconazole nitrate, Nitric acid butoconazole, Oxiconazole Nitrate, Metronidazole mononitrate., nitric acid terconazole (triaconazole) and nitric acid clotrimazole, and other imdazole derivatives as known in the art.Preferred imdazole derivatives in the delivery system of the present invention is a Nitric acid butoconazole.
This delivery system can be made up of the inner phase unit cell.These unit cell are basic, indivisible repetitives of this system.Inner phase can be non-lipoid, can be miscible with water, and can comprise water, glycerol or their combination.Inner phase can be heterogenetic, and can be solution, suspension, emulsion or their combination, and can contain at least a portion activating agent.The foreign minister can be a continuous phase, and is lipoid, promptly contains organic compound, is included in the water insoluble but be dissolved in neutral fat, fatty acid, wax, phospholipid, vaseline, fatty acid monobasic alcohol ester and the mineral oil of alcohol, ether, chloroform or other fat solvent.
Can carry out general classification to this delivery system, for example, suspension, suppository, foam in emulsion, emulsion/dispersion, two emulsion, the emulsion, or other classification well known in the art.Therefore, in embodiments of the invention, the form of this delivery system can change.In one embodiment of the invention, this system is that composition is the Emulsion of cream forms.Other embodiment of the present invention comprises lotion, gel, foam and various Emulsion.The range of viscosities of embodiment preferred is about 5000 to 2000000 centipoises.In addition, other embodiment of the present invention comprises about 5000-750000 centipoise, liquid, semisolid and the solid of preferred 350000-650000 centipoise.Optimizing viscosity can be so that this delivery system be implemented in the maximum bioadhesion on the vaginal canal.
This delivery system is the form of medium emulsion or high internal phase ratio preferably, and internal-phase ratio is the ratio of foreign minister and inner phase.What of system the representative of this ratio account in the percent by volume inner phase of system.In embodiments of the invention, this ratio can be at least 70 volume %, preferred at least 75 volume %, and more preferably at least 80 volume % are more preferably up to about 90 volume %.
Release characteristics of the present invention is the High Internal Phase Emulsion product that the present invention shows.Emulsifying agent, adjuvant, emulsifying agent or other excipient, as glyceryl monostearate, a glyceryl isostearate, methyl parahydroxybenzoate, propyl p-hydroxybenzoate, and general oils, glyceride, sucrose ester, sorbitan esters, poly-sorbitol ester, stearoyl lactate (stearoyl lactylates), lecithin and other similar compounds, produce the emulsifying bead of forming by non-active ingredient.This bead contains the reservoir of activating agent.These beads slowly disperse when using, that is, this bead is tending towards seeking and comprises surface or thin film, and local disperse (that is, in vaginal canal) of this bead, thereby form " film " that contains in a period of time with the bead of controlled release pattern release bioactive agent.This process continues for some time, and for example, therefore is commonly referred to " controlled release " to reaching ten days or longer in three hours.
Bio-adhesive properties of the present invention is the High Internal Phase Emulsion product that the present invention shows.The emulsifying bead volume of being made up of excipient (example is listed in above) is little, but has high relatively surface area.Surface area and surface nature make this bead by multiple physical bond molecular force, as Van der Waals force or hydrogen bond and with people's tissue interaction.These adhesions are compared with less continuous phase or the outer phase volume of forming emulsion owing to high emulsion internal-phase ratio strengthens, and the number of the bead that these are minimum is very many.
The application is incorporated in and authorized Riley on November 30th, 1999, the United States Patent (USP) 5,266 of Jr. (" Riley "), and 329 is for referencial use.Delivery system of the present invention and conventional delivery system, at least one variation that is included in disclosed delivery system in the patent of Riley is the stability of delivery system.Propylene glycol can influence the stability and the diffusion velocity of this delivery system.Can comprise propylene glycol in the preparation of this delivery system as solvent, it helps the active component of this delivery system of dissolving, as imidazoles, as Nitric acid butoconazole.The known propylene glycol that in conventional formulation, uses 5.00 weight %.
In embodiments of the invention, the amount of the propylene glycol that exists can be for about 1.0 to about 4.0 weight %, be preferably about 3.5 to about 3.85 weight %, most preferably be about 3.75 weight %, promptly, compare with believe the 5.00 weight % that need in the delivery system of prior art, the amount of propylene glycol has reduced about 25%.
An exemplary of delivery system of the present invention is as follows:
The Nitric acid butoconazole emulsifiable paste, 2.0%
| Composition | Wt％ |
| Pure water, USP | 39.069 |
| Sorbitol solution, USP | 39.978 |
| Propylene glycol, USP | 3.75 |
| Disodiumedetate, USP | 0.050 |
| Nitric acid butoconazole, USP | 2.000 |
| Mineral oil, USP | 8.032 |
| Polyglycereol 3-oleate | 2.713 |
| Glycerol one isostearate | 2.713 |
| Microwax, NF | 0.452 |
| Hydrophobic silica | 1.013 |
| Methyl parahydroxybenzoate, PF | 0.180 |
| Propyl p-hydroxybenzoate, NF | 0.050 |
The delivery system of some embodiment at least of the present invention improves to some extent with respect to delivery system well known in the art by the amount that reduces propylene glycol in the preparation.The minimizing of propylene glycol does not influence the internal phase emulsions ratio, and it is greater than 70%, and it does not hinder emulsion to form yet.In addition, the minimizing of the propylene glycol of use has realized unpredictable result, and it is highly beneficial and useful for medicine and medical domain.
Delivery system of the present invention has overcome the restriction of prior art.For example, the amount that reduces propylene glycol is improved the diffusion velocity of the pharmaceutically active agents in the delivery system when keeping its useful pharmaceutical properties and effectiveness.
In addition, the delivery system of embodiment of the present invention shows physical property, as bioadhesive be separated and the suitable relevant physical stability that may increase of anti-dispersibility of maintenance in long-time.The physical property of total increase of delivery system of the present invention provides more effective product to consumer, and the treatment of more optimizing in vaginal canal, that is, emulsion-stabilizing and have the diffusion velocity control of the active pharmaceutical ingredient of improvement, thus more effective.At last, the stability of increase may provide the storage life of increase in uncontrollable zone in temperature, and then makes this delivery system to be used by more people.
Exemplary of the present invention has been described according to above-mentioned advantage.Should be understood that these embodiment only are illustrations of the present invention.Many variants and modification are clearly to those skilled in the art.
Claims (25)
1. delivery system, it comprises:
(i) butoconazole of effective dose or its pharmaceutically acceptable salt;
(ii) one or more pharmaceutically acceptable excipient, it is selected from glyceryl monostearate, a glyceryl isostearate, methyl parahydroxybenzoate, propyl p-hydroxybenzoate, oils, glyceride, sucrose ester, sorbitan esters, poly-sorbitol ester, stearoyl lactate and lecithin, and this excipient makes activating agent be released into the site in the vaginal canal in a controlled manner; And
(iii) 4.0 weight % or propylene glycol still less;
This delivery system be under 86 temperature, store inner phase after at least one month with outside compare emulsion greater than 70%.
2. according to the delivery system of claim 1, the agent of wherein said imidazole type antifungal activity account for described delivery system total weight percent 1.5% to 3%.
3. according to the delivery system of claim 1, wherein said delivery system comprises the hydrophilic composition with the stereometer at least 70% of this delivery system.
4. according to the delivery system of claim 1, wherein said delivery system comprises the hydrophilic composition with the stereometer at least 80% of this delivery system.
5. according to the delivery system of claim 3, wherein said delivery system comprises with the stereometer of this delivery system up to 90% hydrophilic composition.
6. according to the delivery system of claim 1, wherein said system shows the bioadhesion to the vaginal canal wall.
7. according to the delivery system of claim 1, wherein said delivery system comprises 3.75 weight % or propylene glycol still less.
8. according to the delivery system of claim 1, wherein said delivery system comprises the propylene glycol of 1.0 weight % to 4.0 weight % scopes.
9. according to the delivery system of claim 1, wherein said delivery system has the internal phase emulsions ratio greater than 70% after storing above one month under 86 the temperature.
10. according to the delivery system of claim 1, wherein said delivery system is stored the internal phase emulsions ratio that has at least after two months greater than 70% under 86 temperature.
11. according to the delivery system of claim 1, wherein said delivery system has the internal phase emulsions ratio greater than 70% at least after storing six months under 86 the temperature.
12. according to the delivery system of claim 1, wherein said delivery system has the internal phase emulsions ratio greater than 70% after storing at least one year under 86 the temperature.
13. according to the delivery system of claim 1, wherein said delivery system makes the agent of described imidazole type antifungal activity at least three hours controlled release site to the vaginal canal.
14. according to the delivery system of claim 1, wherein said delivery system is that viscosity is the liquid or the semi-solid form of 5000 to 2000000 centipoises.
15. according to the delivery system of claim 14, wherein said delivery system is that viscosity is the liquid or the semi-solid form of 5000 to 750000 centipoises.
16. according to the delivery system of claim 15, wherein said delivery system is that viscosity is the liquid or the semi-solid form of 350000 to 650000 centipoises.
17. according to the delivery system of claim 1, the agent of described imidazole type antifungal activity exists with 1% to 10% scope of described delivery system total weight percent.
18. according to the delivery system of claim 1, the agent of wherein said imidazole type antifungal activity exists with 1.5% to 3% scope of described delivery system total weight percent, and comprises:
The propylene glycol of 1.0% to 4.0% scope of described delivery system total weight percent.
19. a delivery system that is suitable for treating the woman's vaginal cavity fungal infection, it comprises:
30.0 the water of weight % to 50.0 weight %;
The sorbitol solution of 30 weight % to 50 weight %;
3.0 the propylene glycol of weight % to 4.0 weight %;
0.02 the disodiumedetate of weight % to 0.08 weight %;
1.5 butoconazole or its pharmaceutically acceptable salt of weight % to 2.5 weight %;
7.0 the mineral oil of weight % to 9.0 weight %;
2.0 polyglycereol-3-oleate of weight % to 3.5 weight %;
2.0 glycerol one isostearate of weight % to 3.5 weight %;
0.2 the microwax of weight % to 0.80 weight %;
0.5 the hydrophobic silica of weight % to 1.5 weight %;
0.1 the methyl parahydroxybenzoate of weight % to 0.3 weight %; With
0.02 the propyl p-hydroxybenzoate of weight % to 0.08 weight %.
20. according to the delivery system of claim 18, wherein said delivery system comprises:
37.819 the water of weight %;
39.978 the Sorbitol of weight %;
3.750 the propylene glycol of weight %;
0.050 the disodiumedetate of weight %;
2.000 the butoconazole of weight % or its pharmaceutically acceptable salt;
8.032 the mineral oil of weight %;
2.713 the polyglycereol of weight %-3-oleate;
2.713 glycerol one isostearate of weight %;
0.452 the microwax of weight %;
1.013 the hydrophobic silica of weight %;
0.180 the methyl parahydroxybenzoate of weight %; With
0.050 the propyl p-hydroxybenzoate of weight %.
21. a delivery system that is suitable for treating the woman's vaginal cavity fungal infection, it is made up of following institute basically:
The water of 35 weight % to 45 weight %;
The sorbitol solution of 35 weight % to 45 weight %;
3.0 the propylene glycol of weight % to 4.0 weight %;
0.02 the disodiumedetate of weight % to 0.08 weight %;
1.5 butoconazole or its pharmaceutically acceptable salt of weight % to 2.5 weight %;
7.0 the mineral oil of weight % to 9.0 weight %;
2.0 polyglycereol-3-oleate of weight % to 3.5 weight %;
2.0 glycerol one isostearate of weight % to 3.5 weight %;
0.02 the microwax of weight % to 0.08 weight %;
0.5 the hydrophobic silica of weight % to 1.5 weight %;
0.1 the methyl parahydroxybenzoate of weight % to 0.3 weight %; With
0.02 the propyl p-hydroxybenzoate of weight % to 0.08 weight %.
22. the method for the delivery system of each of preparation claim 1 to 21, this method comprises:
With the butoconazole of described effective dose or the mixed with propylene glycol of its pharmaceutically acceptable salt, described one or more pharmaceutically acceptable excipient and described amount.
23. according to the method for claim 22, wherein said butoconazole or its pharmaceutically acceptable salt exist with the scope of 1.5 weight % to 3 weight %.
24. a delivery system that comprises applicator, it comprises: be used for compactness, prefill, the i.e. applicator of usefulness to the vaginal canal administered medicaments, described applicator has long and narrow body, and it has near-end to bestow end and far-end prehension end; Described body has enough length with the desired locations administered medicaments in vaginal canal; The proximal part of this long and narrow body forms reservoir, and it is suitable for holding the medicine of scheduled volume; The distal portions of this long and narrow body forms piston chamber; Locking device is positioned at the end of bestowing of this reservoir, and propulsion plant then is positioned at its far-end, is positioned at the joint of reservoir and piston accessory chamber; The telescopic piston rod accessory that is connected with stopping means is in order to limiting scalable extension, and prevents to be connected in the flexible destruction of the piston rod accessory of propulsion plant; Be used to operate the grip device of described telescopic piston rod accessory; Described medicine is each a delivery system of claim 1 to 21.
25. the purposes of the delivery system of each of claim 1 to 21 in the preparation medicine, this medicine is used for the treatment of the woman's vaginal cavity fungal infection.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58627304P | 2004-07-08 | 2004-07-08 | |
| USPCT/US04/22058 | 2004-07-08 | ||
| PCT/US2004/022058 WO2006016869A1 (en) | 2004-07-08 | 2004-07-08 | Delivery system |
| US60/586,273 | 2004-07-08 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005800002434A Division CN1771023A (en) | 2004-07-08 | 2005-07-08 | Delivery system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102188375A true CN102188375A (en) | 2011-09-21 |
Family
ID=35787422
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011101190673A Pending CN102188375A (en) | 2004-07-08 | 2005-07-08 | Delivery system |
| CNA2005800002434A Pending CN1771023A (en) | 2004-07-08 | 2005-07-08 | Delivery system |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005800002434A Pending CN1771023A (en) | 2004-07-08 | 2005-07-08 | Delivery system |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1765452A4 (en) |
| CN (2) | CN102188375A (en) |
| AU (2) | AU2004100776A4 (en) |
| BR (1) | BRPI0513066A (en) |
| CA (1) | CA2572919A1 (en) |
| CZ (1) | CZ15068U1 (en) |
| ES (1) | ES1060042Y (en) |
| FR (1) | FR2872702B3 (en) |
| MX (2) | MXPA04007681A (en) |
| NL (1) | NL1026978C1 (en) |
| NZ (1) | NZ552406A (en) |
| RU (1) | RU2379027C2 (en) |
| WO (2) | WO2006016869A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108371746A (en) * | 2015-09-18 | 2018-08-07 | 赵坚 | A kind of device for administration of drugs of the externally applied drug anti-dropout of gynaecology |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2008651A1 (en) * | 2007-06-26 | 2008-12-31 | Drug Delivery Solutions Limited | A bioerodible patch |
| EP2100632A1 (en) | 2008-03-11 | 2009-09-16 | Pantarhei Devices B.V. | Applicator device for body cavity |
| US8308678B2 (en) | 2008-09-23 | 2012-11-13 | Mcneil-Ppc, Inc. | Pre-filled applicator device |
| EP2359750A1 (en) | 2010-02-15 | 2011-08-24 | Delphi Bioscience B.V. | Screening device with valve |
| FR2968004B1 (en) | 2010-11-29 | 2013-06-28 | Sojasun Technologies | BIODEGRADABLE NATURAL FILMS BASED ON CO-PRODUCTS FROM INDUSTRIAL PROCESSES FOR SEED TREATMENT. |
| RU2538703C2 (en) * | 2013-03-12 | 2015-01-10 | Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") | Pharmaceutical composition for treating vaginal candidiasis and method for preparing it |
| CA3101380A1 (en) * | 2018-06-11 | 2019-12-19 | The Procter & Gamble Company | Methods and applicators for treating vaginal conditions |
| CN112716796B (en) * | 2018-12-11 | 2022-07-08 | 管云 | Power-assisted medicine dispensing device |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4636202A (en) * | 1984-07-27 | 1987-01-13 | Syntex (U.S.A.) Inc. | Medicament applicator with plunger assembly and automatically-openable closure therefor |
| US5266329A (en) * | 1985-10-31 | 1993-11-30 | Kv Pharmaceutical Company | Vaginal delivery system |
| US5536743A (en) * | 1988-01-15 | 1996-07-16 | Curatek Pharmaceuticals Limited Partnership | Intravaginal treatment of vaginal infections with buffered metronidazole compositions |
| ES2133090B1 (en) * | 1997-02-21 | 2000-04-01 | Uriach & Cia Sa J | NEW APPLICATOR FOR THE ADMINISTRATION OF SEMI-SOLID MEDICATIONS. |
| US6403576B1 (en) * | 1998-08-24 | 2002-06-11 | The United States Of America As Represented By The Secretary Of The Navy | Antifungal and antiparasitic compounds |
| US6740333B2 (en) * | 2000-07-07 | 2004-05-25 | Anestic Aps | Suppository and composition comprising at least one polyethylene glycol |
-
2004
- 2004-07-08 MX MXPA04007681A patent/MXPA04007681A/en unknown
- 2004-07-08 WO PCT/US2004/022058 patent/WO2006016869A1/en active Application Filing
- 2004-08-03 CZ CZ200415701U patent/CZ15068U1/en not_active IP Right Cessation
- 2004-09-06 NL NL1026978A patent/NL1026978C1/en not_active IP Right Cessation
- 2004-09-09 ES ES200402091U patent/ES1060042Y/en not_active Expired - Fee Related
- 2004-09-15 AU AU2004100776A patent/AU2004100776A4/en not_active Expired
- 2004-12-22 FR FR0413770A patent/FR2872702B3/en not_active Expired - Lifetime
-
2005
- 2005-07-08 NZ NZ552406A patent/NZ552406A/en not_active IP Right Cessation
- 2005-07-08 RU RU2007104782/14A patent/RU2379027C2/en not_active IP Right Cessation
- 2005-07-08 WO PCT/US2005/024200 patent/WO2006014572A1/en active Application Filing
- 2005-07-08 MX MX2007000109A patent/MX2007000109A/en active IP Right Grant
- 2005-07-08 CA CA002572919A patent/CA2572919A1/en not_active Abandoned
- 2005-07-08 BR BRPI0513066-2A patent/BRPI0513066A/en not_active IP Right Cessation
- 2005-07-08 EP EP05769226A patent/EP1765452A4/en not_active Withdrawn
- 2005-07-08 CN CN2011101190673A patent/CN102188375A/en active Pending
- 2005-07-08 AU AU2005269844A patent/AU2005269844A1/en not_active Abandoned
- 2005-07-08 CN CNA2005800002434A patent/CN1771023A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108371746A (en) * | 2015-09-18 | 2018-08-07 | 赵坚 | A kind of device for administration of drugs of the externally applied drug anti-dropout of gynaecology |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ552406A (en) | 2010-07-30 |
| FR2872702A3 (en) | 2006-01-13 |
| NL1026978C1 (en) | 2006-01-10 |
| CZ15068U1 (en) | 2005-01-31 |
| WO2006014572A1 (en) | 2006-02-09 |
| EP1765452A1 (en) | 2007-03-28 |
| ES1060042Y (en) | 2005-11-01 |
| MX2007000109A (en) | 2007-03-26 |
| WO2006016869A1 (en) | 2006-02-16 |
| FR2872702B3 (en) | 2006-06-02 |
| ES1060042U (en) | 2005-07-16 |
| CN1771023A (en) | 2006-05-10 |
| RU2007104782A (en) | 2008-08-20 |
| AU2004100776A4 (en) | 2004-11-18 |
| AU2005269844A1 (en) | 2006-02-09 |
| MXPA04007681A (en) | 2006-01-12 |
| BRPI0513066A (en) | 2008-04-22 |
| CA2572919A1 (en) | 2006-02-09 |
| RU2379027C2 (en) | 2010-01-20 |
| EP1765452A4 (en) | 2012-11-28 |
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Legal Events
| Date | Code | Title | Description |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110921 |