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WO2011121604A2 - Formulation de pulvérisation vaginale liquide pour le traitement d'une infection vaginale fongique - Google Patents

Formulation de pulvérisation vaginale liquide pour le traitement d'une infection vaginale fongique Download PDF

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Publication number
WO2011121604A2
WO2011121604A2 PCT/IN2011/000202 IN2011000202W WO2011121604A2 WO 2011121604 A2 WO2011121604 A2 WO 2011121604A2 IN 2011000202 W IN2011000202 W IN 2011000202W WO 2011121604 A2 WO2011121604 A2 WO 2011121604A2
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WO
WIPO (PCT)
Prior art keywords
vaginal
vaginitis
lactic acid
amount
spray
Prior art date
Application number
PCT/IN2011/000202
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English (en)
Other versions
WO2011121604A3 (fr
WO2011121604A9 (fr
Inventor
Rajni Gulabdas Patel
Jigar Hasmukhbhai Patel
Arun Chimanlal Shah
Nilay Bhartendu Pandya
Original Assignee
Lincoln Pharmaceuticals Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lincoln Pharmaceuticals Limited filed Critical Lincoln Pharmaceuticals Limited
Publication of WO2011121604A2 publication Critical patent/WO2011121604A2/fr
Publication of WO2011121604A3 publication Critical patent/WO2011121604A3/fr
Publication of WO2011121604A9 publication Critical patent/WO2011121604A9/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/12—Aerosols; Foams

Definitions

  • the present invention relates to a synergistic liquid vaginal spray composition. More particularly, the present invention relates to a synergistic vaginal spray composition containing lactic acid and at least one antifungal agent for the treatment of vaginal fungal infections such as vulvovaginal candidiasisor "yeast" infection bacterial vaginosis. Trichomoniasis, Chlamydia vaginitis. Gonococcal vaginitis. Viral vaginitis. Noninfectious vaginitis. The present invention also relates to process for preparation of the said composition.
  • the normal ecosystem of the vagina involves many different organisms that are involved in a system of checks and balances. No other concept in vaginal health is as important as the state of the ecosystem of the vagina.
  • the flora that colonizes the vagina takes place in the birth canal during delivery, and the flora that is established in the newborn girl must therefore consist -of the same strains as in the mother.
  • the vaginal environment of a newborn changes during the first month, then again at prepuberty, puberty, during the reproductive years and post-menopausally. Additionally, the cyclic hormonal changes of the menstrual cycle also influence the vaginal ecosystem. It is a variable state throughout a woman's lifetime, but nothing is more key to this ecosystem than lactobacil!us.
  • the range of bacterial types isolated is immense, including Staphylococcus species, Garnerella vaginalis. Streptococcus species, Bacteriodes species, Lactobacillus species, Mobiluncus, Candida species, (most commonly Candida albicans), and more.
  • the predominant organisms isolated from the normal vagina are members of the Lactobacillus genus.
  • One species of bacteria inhibits another and an elegant combination of pH, vaginal immunity, hormonal activity and the community of organisms that occupy the vagina interact in a manner in which bacterial overgrowth is controlled, unless the well- established mechanism of balance is thrown off by one factor or another.
  • a flora that inhabits vaginal surface can be categorized as "resident" flora and "transient” flora.
  • “Resident” flora generally refers to microflora which generally “colonizes” a particular tissue surface. In case of vagina the flora mainly comprises Lactobacilli genus. "Transient” flora generally refers to the flora which may inhabit a tissue surface, may be for days to months, but never more than that. The transient flora is mainly comprises pathogenic organism, which are, in healthy people, kept under check by the resident flora. Resident flora, in effect, acts as a first line of defense against variety of pathogens and pathologies.
  • Lactobacillus helps in maintaining the environment of vagina. Lactic acid is produced by the metabolism of lactobacillus and although there may be other ways in which the vagina maintains its normal acidic environment, the role of lactobacilli seems evident. Lactobacilli thrive at an acidic pH of 3.5-4.5 and these values are indeed found in the normal vagina throughout the menstrual cycle.
  • Lactobacilli have also been shown to interfere with how pathogenic bacteria adhere and colonize the cells of the vagina. Lactobacilli also act directly as antibacterials and may function as an immune stimulant locally in controlling microbial levels in the vagina.
  • Antifungal drugs/agents are medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained on doctor's prescription or purchased over-the-counter.
  • Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism without dangerous effects on the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus fungal and human cells are similar at the molecular level. This makes it more difficult to find or design drugs that target ffhgi without affecting human cells. Consequently, many antifungal drugs cause side-effe!ets. Some of these side-effects can be life-threatening if the drugs are not used properly.
  • the imidazole and triazole drugs are synthetic antifungal drugs that inhibit the enzyme cytochrome P450 14a-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell membrane synthesis. These drugs also block steroid3 ⁇ 4synthesis in humans.
  • lactic acid and an antifungal agent inhibits proliferation of pathogenic organisms, particularly fungi, by making the environment unfavorable for the pathogens to thrive, a combined, synergistic use may also be envisaged.
  • US Publication No. 20070286812 discloses a nasal formulation comprising pharmaceutical antifungal agents along with and natural antifungal agents (Lactobacillus species) in a solid, liquid or aerosol form.
  • US Patent No. 7125708 relates to a composition comprising Lactobacillus strain NCIMB 41 1 14 and an antifungal agent for the treatment of yeast infection.
  • Indian Patent Application No. 675/KOL/2004 (EPl 506781 ) disclosed a vaginal care composition comprising viable Lactobacillus and/or Bifidobacterium microorganisms; non-viable Saccharomyces cultures; vitamin A/retinol, and zinc.
  • European Patent No. 1764100 filed by Johnson & Johnson Consumer Companies, Inc. discloses a buffered composition for lowering vaginal pH.
  • the said Patent suggests that lactic acid and an antifungal agent for lowering and maintaining pH of vaginal surface in range of 3 to 4.5.
  • the invention is directed to reducing self- perceived vaginal odor by maintaining the pH in normal range.
  • composition in the said Patent is in the form of suspensions, emulsions, clear and opaque gels, semisolid systems, including ointments, pastes, oil-in-water (o/w) creams, semisolid emulsions with solid internal phases, semisolid emulsions with fluid internal phases, vaginal suppositories, insertable tablets, soft or hard gelatin capsules and the like.
  • US Publication No. 2010173965 relates to use of an azole compound with an organic acid with a view to enhance absorption.
  • suppositories have attained some success, they have some disadvantages.
  • Most of the current commercial vaginal suppositories either melt or dissolve in the vaginal tract into an oily or aqueous liquid. This resulting liquid in turn tends to leak out or is expelled out of the vaginal cavity resulting either in soiled clothing and/or inferior efficacy.
  • the applicator is very long, e.g. suppository (approx. 1 1 cm) and gel (approx. 12 cm) which produces more risk and fear to the patients.
  • the present invention provides a synergistic combination of lactic acid and at least one antifungal agent in liquid vaginal spray dosage form for treatment of vaginal fungal infection such as vulvovaginal candidiasis or "yeast” infection bacterial vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Non-infectious vaginitis.
  • vaginal fungal infection such as vulvovaginal candidiasis or "yeast” infection bacterial vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Non-infectious vaginitis.
  • composition of the present invention afford a better patient compliance, better bioavailability, when compared to painful intramuscular injections, suppositories such as vaginal capsules or tablets and messy application of gel and creams, as the present formulation is in solution form that can administered by spraying method.
  • the antifungal drugs of the present invention give the local as well as systemic effect via vaginal route whereas lactic acid maintains the desired vaginal pH levels. Maintenance of vaginal pH helps to cover the loss of lactic acid due to infection, which is otherwise naturally produced by lactobacilli into vagina.
  • the present invention provides a process for preparing the said liquid vaginal spray composition.
  • the invention provides a synergistic liquid vaginal spray dosage form to provide local as well as systemic effect, comprising therapeutically effective amount of at least one antifungal agent along with lactic acid, useful for the treatment of vaginal fungal infections like vulvovaginal.
  • the invention provides novel mode of delivery for treatment of vaginal fungal infections like Candidiasis or "yeast” infection Bacterial Vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Noninfectious vaginitis which provides better patient compliance as compare to painful intramuscular injections, as it is in solution form.
  • vaginal fungal infections like Candidiasis or "yeast” infection
  • Bacterial Vaginosis Trichomoniasis
  • Chlamydia vaginitis Gonococcal vaginitis
  • Viral vaginitis Viral vaginitis
  • Noninfectious vaginitis which provides better patient compliance as compare to painful intramuscular injections, as it is in solution form.
  • the invention provides a liquid vaginal spray dosage form to provide local as well as systemic effect, comprising therapeutically effective amount of at least one antifungal agent along with lactic acid in association with a unique blend of solvents and co-solvents, useful for the treatment of vaginal fungal infections like Candidiasis or "yeast" infection bacterial vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Non-infectious vaginitis.
  • the blend will be of solvents and co-solvents in their suitable ratio, the ratio of solvent and co-solvent will depends on the drug.
  • composition of the present invention further comprises other pharmaceutically acceptable polymers mainly used for bio adhesion and to maintain proper viscosity of formulation.
  • Suitable polymer are selected from ethyl cellulose, polyvinylpyrrolidone, hydroxyl propyl methyl cellulose, hydroxyl propyl cellulose, hydroxyl ethyl cellulose, ethyl cellulose either alone or in combination is present in an amount of 0.5 to 10%. ,
  • composition of the present invention has better patient compliance than vaginal tablets or capsule or painful intramuscular injection and messy application of gel and creams, as the current formulation is dispensed in a mist form to cover a larger area of vaginal cavity with very small amount of dispensed volume, thus increasing the bioavailability of the said composition.
  • Suitable antifungal agents are selected from the group of Miconazole, Ketoconazole, Clotrimazole, Econazole, Bifonazole, Butoconazole, Fenticonazole, Isoconazole, Oxiconazole, Sertaconazole, Sulconazole, Tioconazole, Griseofulvin, Fluconazole Fosfluconazole, Itraconazole, Posaconazole, Voriconazole, Amorolfine, Butenafine, Naftifine, Terbinafine, Terbinafine, Natamycin, Nystatin, Amphotericin B, Thiabendazole, Anidulafungin, Caspofungin, MicafunginFlucytosineor their pharmaceutically acceptable salts alone or in combination thereof.
  • the said antifungal agent(s) is present in the range of 5% to 25% to achieve the desired therapeutic benefit.
  • the said lactic acid is present in range of 2-10 mg preferably 4 mg i.e. approximately 1 to 10%.
  • the ratio of antifungal agent and lactic acid is 25: 1 .
  • Suitable solvents and co-solvents are selected from group of polyethylene glycol, diethylene glycol monoethyl, glycofurol, benzyl alcohol, labrasol, Benzyl benzoate and Ethyl oleate, propylene glycol, Diethylene Glycol Monoethyl Ether, ethyl alcohol, cremophore ELP, Solutol, transcutol, capmul, captex and their combinations like in. desired amount of about 5% to 90%.
  • composition of the present invention can be prepared by the conventional methods such as simple mixing wherein solvents are mixed in the vessel followed by addition of polymer and an antifungal agent.
  • the mixture is heated under continuous stirring to achieve complete dissolution of the active agent and the excipients and then the said mixture cooled.
  • lactic acid is added under continuous stirring and the -formulation so obtained is stored in airtight closed container in light resistant area.
  • the invention provides a spray dispenser comprising therapeutically effective amount an antifungal agent with lactic acid in association with a unique blend of solvents and co-solvents.
  • the composition is filled in a convenient container that can give the formulation in form of fine droplets or mist.
  • the container assembly is specifically designed to provide drug dispensing directly into vagina in unit dosage form. Hence, it is easy to deliver in to vaginal orifice.
  • the composition of the present invention is administered via metered dosing spray nozzle to deliver accurate dose of drug.
  • the invention provides a composition which is in a liquid vaginal spray dosage form comprising therapeutically effective amount of an antifungal agent with lactic acid in association with a unique blend of solvents and co-solvents, wherein the said composition does not crystallize at very low temperature during storage.
  • the present invention provides a liquid vaginal spray dosage comprising therapeutically effective amount of Clotrimazole in combination with lactic acid in unique blend of solvent, useful for treatment of infections such as valvovaginal candidiasisor "yeast” infection, bacterial vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Noninfectious vaginitis.
  • infections such as valvovaginal candidiasisor "yeast” infection, bacterial vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Noninfectious vaginitis.
  • Total volume of the formulation is 5 ml and Clotrimazolein its base form is present in amount of 25% in combination with lactic acid 1 %. Ratio of the both actives in the » - formulation is 25: 1 .
  • Other excipients such as polyethylene glycol is present in an amount ;, ; of 23.9%, diethylene glycol monoethyl ether in an amount of 23.8%, glycofurol in an amount of 23.8%, benzyl alcohol in ' an amount of 0.5% and ethyl cellulose in an amount >, of 2%.
  • the present invention provides a method of treating fungal infections such as Vulvovaginal Candidiasis or "yeast" infection, bacterial vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Noninfectious vaginitis, which comprises administering 'an effective amount' of the 'liquid vaginal spray composition comprising at least one antifungal agent with lactic acid' to the subject suffering from the said fungal infections.
  • the subject mentioned herein is human.
  • the invention further discloses use of the 'spray composition of the invention comprising at least one antifungal agent with lactic acid' intended to treat fungal infections such as vulvovaginal Candidiasis or "yeast” infection, bacterial vaginosis, Trichomoniasis, Chlamydia vaginitis, Gonococcal vaginitis, Viral vaginitis, Noninfectious vaginitis.
  • Clinical Trial was conducted to study improved efficacy of vaginal spray comprising Clotrimazole and lactic acid of present invention (described in example 3) on human subjects with vulvovaginal candidiasis.,
  • Clotrimazole with lactic acid liquid vaginal spray is highly effective in patients suffering from the infection of valvovaginal candidiasis.
  • Step 1 Weighing accurately Polyethylene Glycol 400, Diethylene Glycol Monoethyl Ether, Glycofurol, and Benzyl Alcohol in S.S.Vessel and mixing all by continuous stirring;
  • Step 2 Weighing accurately Ethyl cellulose and dissolving into step 1 ; : Step 3: Dissolving Clotrimazole IP into mixture of Polyethylene Glycol 400, Diethylene Glycol Monoethyl Ether, Glycofurol, and Benzyl Alcohol, Ethyl cellulose by heating the mixture at 70°C in Manufacturing Vessel with continuous stirring;
  • Step 4 Then, immediately transferring in to another clean vessel and allowing it to cool;
  • Step 5 After cooling adding lactic acid with stirring;
  • Step 6 Store the formulation in airtight closed container in light resistant area.
  • Step 1 Weighing accurately Polyethylene Glycol 400, Labrasol, Glycofurol, and Benzyl
  • Step 2 Weighing accurately PVP-K 30 and dissolving into step 1;
  • Step 3 Dissolving Fluconazole into mixture of Polyethylene Glycol 400, Labrasol,
  • Step 4 Then, immediately transferring in to another clean vessel and allowing it to cool;
  • Step 5 After cooling adding lactic acid with stirring;
  • Step 6 Store the formulation in airtight closed container in light resistant area.
  • Step 1 Weighing accurately Polyethylene Glycol 400, Labrasol, Glycofurol, and Benzyl Alcohol in S.S. Vessel and mixing all by continuous stirring;
  • Step 2 Weighing accurately PVP-K 30 and dissolving into step 1 ;
  • Step 3 Dissolving Clotrimazole into mixture of Polyethylene Glycol 400, Labrasol, Glycofurol, and Benzyl Alcohol, PVP-K 30 by heating the mixture at 70°C in Manufacturing Vessel with continuous stirring;
  • Step 4 Then, immediately transferring in to another clean vessel and allowing it to cool ;
  • Step 5 After cooling adding lactic acid with stirring;
  • Step 6 Store the formulation in airtight closed container in light resistant area.
  • Step 1 Weighing accurately Polyethylene Glycol 400, Labrasol, Glycofurol, and Benzyl
  • Step 2 Weighing accurately PVP-K 30 and dissolving into step 1 ;
  • Step 3 Dissolving Econazole into mixture of Polyethylene Glycol 400, Labrasol,
  • Step 4 Then, immediately transferring in to another clean vessel and allowing it to cool ;
  • Step 5 After cooling adding lactic acid with stirring;
  • Step 6 Store the formulation in airtight closed container in light resistant area.
  • Step 1 Weighing accurately Polyethylene Glycol 400, Labrasol, Glycofurol, and Benzyl Alcohol in S.S. Vessel and mixing all by continuous stirring;
  • Step 2 Weighing accurately PVP-K 30 and dissolving into step 1 ;
  • Step 3 Dissolving Miconazole into mixture of Polyethylene Glycol 400, Labrasol, * " Glycofurol, and Benzyl Alcohol, PVP-K 30 by heating the mixture at 70°C in Manufacturing Vessel with continuous stirring;
  • Step 4 Then, immediately transferring in to another clean vessel and allowing it to cool;
  • Step 5 After cooling adding lactic acid with stirring;
  • Step 6 Store the formulation in airtight closed container in light resistant area.
  • Clotrimazole 100mg/0.8gm
  • Lactic acid vaginal spray 4mg/0.8gm
  • Duration of treatment 6 days Suppression of symptoms was observed and percentage of individual unresolved symptoms was calculated.
  • vaginal clotrimazole eg. cream, gel, suppository etc.
  • vaginal spray preparation comprising Clotrimazole (100 mg/0.8 ml) with Lactic acid (4 mg/ 0.8 ml) has below mentioned advantages as compared to other vulvovaginal antifungal preparations in the market:
  • the container having metered dosing spray nozzle delivers accurate dose of drug in mist form to cover large surface area of vagina and provide a local treatment which is not possible in case of cream or gel formulations which needs to be applied through applicators.
  • Length of nozzle is optimized to insert the nozzle of device (5.4 cm) which can deliver the drug at exact required site into vagina whereas in case of other formulations, the applicator is very long, e.g. suppository (approx. 1 1 cm) and gel (approx. 12 cm) which produces more risk and fear to the patients.
  • the intensity of burning sensation is very minor and comfort level is higher hence, patient compatible in case of the composition of present invention as compared to suppository, cream and gel formulations.
  • the composition is non-sticky as compared to creams and gels. Therefore, patients feel easy to administer and more comfortable after application. Drug of the composition gets absorbed without leaving sticky inert particles behind.
  • Lactic acid maintains the desired vaginal pH levels 4-4.5. This helps to cover the loss of lactic acid due to infection, which is otherwise naturally produced by Lactobacilli into vagina.

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

Abstract

L'invention concerne une forme pharmaceutique de pulvérisation vaginale liquide produisant un effet local ainsi qu'un effet systémique, et qui comprend une quantité thérapeutiquement efficace d'au moins un agent antifongique et de l'acide lactique, cette forme pharmaceutique étant destinée à traiter des infections vaginales fongiques telles que la candidose vulvo-vaginale ou la vaginose bactérienne par infection à levures, la trichomonase, la vaginite à chlamydia, la vaginite à gonocoques, la vaginite virale et la vaginite non infectieuse.
PCT/IN2011/000202 2010-03-29 2011-03-24 Formulation de pulvérisation vaginale liquide pour le traitement d'une infection vaginale fongique WO2011121604A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN945/MUM/2010 2010-03-29
IN945MU2010 2010-03-29
IN94MU2011 2011-01-11
IN94/MUM/2011 2011-01-11

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WO2011121604A2 true WO2011121604A2 (fr) 2011-10-06
WO2011121604A3 WO2011121604A3 (fr) 2012-03-15
WO2011121604A9 WO2011121604A9 (fr) 2012-04-19

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2377933A1 (es) * 2011-11-23 2012-04-03 Betelgeux, S.L. Composición para el control de la contaminación fúngica y método de uso.
WO2014026707A1 (fr) * 2012-08-13 2014-02-20 Edko Pazarlama Tanitim Ticaret Limited Sirketi Compositions anti-vaginite à libération et adhérence améliorées
WO2014027006A1 (fr) * 2012-08-13 2014-02-20 Edko Pazarlama Tanitim Ticaret Limited Sirketi Formulations bioadhésives destinées à être utilisées dans l'administration de médicaments
EP3204120A4 (fr) * 2014-10-08 2018-10-10 Pacific Northwest Research Institute Procédés et compositions pour augmenter l'activité d'agents antifongiques
CN109833301A (zh) * 2017-11-29 2019-06-04 天津市保灵动物保健品有限公司 一种犬猫用盐酸特比萘芬风味片及其制备工艺
WO2019201713A1 (fr) * 2018-04-10 2019-10-24 Ligalli B.V. Administration systémique vaginale de médicament
CN112957319A (zh) * 2021-02-05 2021-06-15 王京海 一种抗真菌液及其制备方法和应用
CN113423382A (zh) * 2019-02-19 2021-09-21 萨尔瓦特实验室股份有限公司 单剂量包装的克霉唑液体组合物
CN114452315A (zh) * 2022-03-16 2022-05-10 郑州大学第一附属医院 一种阴道泡腾栓及其制备方法
US12016953B2 (en) 2018-11-30 2024-06-25 Viramal Limited Method of preparing a gelling agent, the gelling agent obtained thereby, and the use of said gelling agent

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Publication number Priority date Publication date Assignee Title
IL271596B2 (en) * 2017-06-22 2024-07-01 Viramal Ltd Emulsion compositions comprising danazol for use in the treatment of an endometrial disease or condition

Family Cites Families (2)

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Publication number Priority date Publication date Assignee Title
US20030130225A1 (en) * 2001-10-16 2003-07-10 Nawaz Ahmad Novel methods of treating local fungal and bacterial infections
US20070292355A1 (en) * 2002-10-25 2007-12-20 Foamix Ltd. Anti-infection augmentation foamable compositions and kit and uses thereof

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013076328A1 (fr) * 2011-11-23 2013-05-30 Betelgeux, S.L. Composition pour lutter contre la contamination fongique et méthode d'utilisation
ES2377933A1 (es) * 2011-11-23 2012-04-03 Betelgeux, S.L. Composición para el control de la contaminación fúngica y método de uso.
WO2014026707A1 (fr) * 2012-08-13 2014-02-20 Edko Pazarlama Tanitim Ticaret Limited Sirketi Compositions anti-vaginite à libération et adhérence améliorées
WO2014027006A1 (fr) * 2012-08-13 2014-02-20 Edko Pazarlama Tanitim Ticaret Limited Sirketi Formulations bioadhésives destinées à être utilisées dans l'administration de médicaments
US12280032B2 (en) 2014-10-08 2025-04-22 Pacific Northwest Research Institute Methods and compositions for increasing the potency of antifungal agents
EP3204120A4 (fr) * 2014-10-08 2018-10-10 Pacific Northwest Research Institute Procédés et compositions pour augmenter l'activité d'agents antifongiques
US11446271B2 (en) 2014-10-08 2022-09-20 Pacific Northwest Research Institute Methods and compositions for increasing the potency of antifungal agents
US10751317B2 (en) 2014-10-08 2020-08-25 Pacific Northwest Research Institute Methods and compositions for increasing the potency of antifungal agents
CN109833301A (zh) * 2017-11-29 2019-06-04 天津市保灵动物保健品有限公司 一种犬猫用盐酸特比萘芬风味片及其制备工艺
WO2019201713A1 (fr) * 2018-04-10 2019-10-24 Ligalli B.V. Administration systémique vaginale de médicament
US11717477B2 (en) 2018-04-10 2023-08-08 Ligalli B.V. Vaginal systemic drug delivery
US12016953B2 (en) 2018-11-30 2024-06-25 Viramal Limited Method of preparing a gelling agent, the gelling agent obtained thereby, and the use of said gelling agent
CN113423382A (zh) * 2019-02-19 2021-09-21 萨尔瓦特实验室股份有限公司 单剂量包装的克霉唑液体组合物
CN112957319A (zh) * 2021-02-05 2021-06-15 王京海 一种抗真菌液及其制备方法和应用
CN114452315B (zh) * 2022-03-16 2023-04-07 郑州大学第一附属医院 一种阴道泡腾栓及其制备方法
CN114452315A (zh) * 2022-03-16 2022-05-10 郑州大学第一附属医院 一种阴道泡腾栓及其制备方法

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WO2011121604A9 (fr) 2012-04-19

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