WO2020190249A1 - Composition pharmaceutique sous forme d'onguent pour le traitement de maladies dermatologiques - Google Patents

Composition pharmaceutique sous forme d'onguent pour le traitement de maladies dermatologiques Download PDF

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Publication number
WO2020190249A1
WO2020190249A1 PCT/UA2020/000012 UA2020000012W WO2020190249A1 WO 2020190249 A1 WO2020190249 A1 WO 2020190249A1 UA 2020000012 W UA2020000012 W UA 2020000012W WO 2020190249 A1 WO2020190249 A1 WO 2020190249A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
ointment
vaseline
dermatological diseases
mupirocin
Prior art date
Application number
PCT/UA2020/000012
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English (en)
Inventor
Ihor Anatoliyovych VYSHNEVSKYY
Original Assignee
Vyshnevskyy Ihor Anatoliyovych
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
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Application filed by Vyshnevskyy Ihor Anatoliyovych filed Critical Vyshnevskyy Ihor Anatoliyovych
Publication of WO2020190249A1 publication Critical patent/WO2020190249A1/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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics

Definitions

  • a pharmaceutical composition in a form of an ointment for treating dermatological diseases in a form of an ointment for treating dermatological diseases
  • the invention relates to pharmaceutics and medicine, namely to drugs in a form of an ointment for treating dermatological diseases.
  • the drug“Triderm” is known (manufactured by“Schering-Plough Labo N. V.”, Belgium) in a form of an ointment for treating dermatosis being sensitive to corticosteroids, when bacterial and/or fungal infections are present (or suspected) caused by microorganisms, which are sensitive to components of the medicament.
  • “Triderm” medicament the optimal medicament for topical treatment of complicated skin and mucosal diseases.
  • “Triderm” combines anti inflammatory, anti-pruritic, anti-allergic and anti-exudative effects of the glucocorticosteroid (GCS) being betamethasone dipropionate with the anti-fungal activity of clotrimazole and wide anti-bacterial activity of gentamicin sulfate.
  • GCS glucocorticosteroid
  • mometasone furoate has a particular interest. Due to its biochemical and pharmacological properties, mometasone furoate found a wide use in the treatment practice, including in pediatry. As compared to other strong corticosteroids during topical use, mometasone furoate leads to less significant side effects, which allows to use it for children aged from 2 to 12. As compared to betamethasone, mometasone furoate demonstrates more expressed anti-inflammatory effect and long duration of action, while having less potential of systemic side effects. Mometasone furoate does not comprise a fluorine atom, thereby causing its high safety as compared to fluorated corticosteroids, which represent a majority of corticosteroids, including betamethasone.
  • a pharmaceutical composition for topical use according to the invention patent of Ukraine No. 107968 C2, IPC: A61K 31/58, A61K 47/06, A61P 17/00, publ. on March 10, 2015 is known, the composition comprising mometasone furoate dispersed in the composition with hexylene glycol, water and oil phase, wherein the components are present in the following ratio: 0.01-0.2 % by weight of mometasone furoate, 5-18 % by weight of hexylene glycol, 20-40 % by weight of water and 25-70 % by weight of the oil phase.
  • the known composition is used for treating or preventing psoriasis, in case of atopic dermatitis (atopic eczema) and other skin diseases.
  • a drawback of the known composition lies in a narrow pharmacological action range caused by a presence of only one active substance therein. Thus, in case of overlay of a bacterial or a fungal infection that is suspected or is probable to be developed, the known composition will have low efficiency.
  • the invention is aimed at providing a highly effective pharmaceutical composition for external use having anti-allergic, anti-bacterial and anti-microbial activity with a minimum risk of occurrence of side effects for treatment of dermatological diseases.
  • a pharmaceutical composition in a form of an ointment for treating dermatological diseases comprising mometasone furoate as an active substance and adjuvants, further comprises active substances being naftifme hydrochloride and mupirocin, as well as macrogolglycerol hydroxystearate 40, vaseline oil and vaseline as adjuvants, wherein the components are taken in the following ratio, g:
  • mometasone furoate (taken on 100% dry matter) 0.10 naftifme hydrochloride (taken on 100% dry matter) 1.00 mupirocin (taken on 100% dry matter) 2.00 macrogolglycerol hydroxystearate 40 8.00 vaseline oil 5.00 vaseline up to 100.00
  • the active substances and the adjuvants, which are comprised in the claimed ointment, are known in the pharmaceutics, however, their quantitative and qualitative combination is novel and is not known from sources of information.
  • Naftifme is a synthetic anti-fungal medicine that belongs to the group of allylamines having a wide action range. According to date of the Cochrane meta analysis, allylamines are more effective than azoles, to which clotrimazole relates. One of such drugs is naftifme that is considered to be more effective than clotrimazole. Naftifme has a number of advantages as compared to other anti fungal medicines. It has a high selectivity against a fungal cell. Naftifme exhibits a high fungicidal activity and minimal intensity of side effects.
  • Naftifme is effective against dermatophytes such as trichophyton, epidermophyton and microsporum, yeast (Candida), mycelial (Aspergillus) and other fungi (e.g., Sporothrix schenckii). Naftifme also exhibits anti-bacterial activity against gram-positive and gram-negative microorganisms, which may case secondary bacterial infections alongside with mycotic abnormalities. Besides, naftifme bears anti-inflammatory properties.
  • Mupirocin is an antibiotic that is firstly isolated from the Pseudomonas fluorescens culture and represents a derivative of a butanoyl nonanoic acid, a mixture of pseudomonic (monocarboxylic) acids, wherein the pseudomonic acid A is predominant (90%), as well as acids B, C and D. Mupirocin strongly suppresses protein and RNA synthesis, while the influence on DNA and creation of a cell wall is expressed in a significantly larger extent. The action of the drug in low concentrations is bacteriostatic, while in high concentrations the bactericidal effect is developed.
  • mupirocin does not have a cross-resistance with other antibiotics. Muriprocin has a rather wide action range. The anti-bacterial efficiency of muripocin is higher as compared to gentamycine, while the microbial resistance occurs more rarely.
  • the formulation of the medicine comprises the following adjuvants: macrogolglycerol hydroxystearate 40, vaseline oil, vaseline.
  • Macrogolglycerol hydroxystearate 40 is a solvent of mupirocin.
  • the vaseline oil is used in the course of a technological process as a dispersion medium when preparing a suspension of mometasone furoate and when preparing a suspension and grinding naftifme hydrochloride, while the vaseline is used as a base of the ointment dispersion medium.
  • Said adjuvants are widely used in the medical practice in a formulation of medicines for the external use.
  • the quantitative ratio of the ointment components is determined experimentally and is optimal for the proposed composition.
  • the claimed pharmaceutical composition may be produced industrially using a standard equipment according to the following technological scheme: preparing the mometasone furoate suspension; preparing the naftifme hydrochloride suspension and grinding particles of naftifme hydrochloride; melting the macrogolglycerol hydroxystearate 40; introducing mupirocin into the molten macrogolglycerol hydroxystearate 40 and its dissolving; melting the vaseline; introducing the mometasone furoate suspension and the naftifme hydrochloride suspension into the molten vaseline, homogenization, cooling up to a temperature (40-45)°C; introducing the mupirocin, homogenization; cooling up to a temperature of 25°C; dosing the medicine into tubes.
  • Opaqueness and white color of the medicine are caused by optical properties of the medicine.
  • Increase of the temperature from 25 °C to 50°C causes reduction of a structural viscosity of the medicine.
  • the proposed pharmaceutical composition in the form of the ointment bears significant advantages over soft drugs, which currently exist on the Ukrainian market, comprising a combination of a glucocorticosteroid, anti-microbial and anti- fungal component.
  • Mometasone furoate is a first one from the group of corticosteroid that does not cause skin atrophy.
  • Active substances being mupirocin and naftifme hydrochloride provide effective anti-microbial conservative activity.
  • the medicine meets the established pharmacopeial requirements raised to non-sterile medicines for the external use, which comprise anti-microbial preservatives.
  • the anti-microbial activity of the studied pharmaceutical composition for treating dermatological diseases has been studied in comparison with the activity of the registered medicine Triderm® ointment (manufactured by“Schering-Plough Labo N. V.”, Belgium).
  • Triderm® ointment manufactured by“Schering-Plough Labo N. V.”, Belgium.
  • UCM Ukrainian Collection of Microorganisms
  • SISC SISC .a. L. A. Tarasevych
  • SE“V.T. Zaytsev Institute of General and Emergency Surgery of NAMS of Ukraine” Kerkiv city, Ukraine.
  • Study of the specific anti-microbial activity of the medicines was conducted by the in vitro diffusion method into a nutritive agar.
  • the studied pharmaceutical composition for treating dermatological diseases has a strong anti microbial activity against representatives of the Staphylococcus and Enterococcus species, exhibits a moderate bacteriological activity against the Escherichia Coli, has a low-grade bacteriological activity against the Micrococcus luteus and Pseudomonas aeruginosa.
  • the studied drugs have not exhibited any activity against the Proteus vulgaris.
  • the obtained experimental data conform with the literature data regarding the anti-microbial activity range of the mupirocin in vitro.
  • the studied pharmaceutical composition has exhibited an adequately stronger anti-bacterial activity against the test strains of the bacteria used in the experimental studies than the reference sample.
  • the studied pharmaceutical composition has a strong fungicidal activity against Aspergillus niger BKFirf 156/7813 and exhibits a moderate fungistatic activity against Aspergillus fumigatus BKPGG-59 / B-770 and representatives of yeast-like fungi of the Candida species (Table 2).
  • the studied pharmaceutical composition is located at the level of the reference sample.
  • Example 3 Clinical studies of the proposed pharmaceutical composition in the form of the ointment in the treatment of atopic dermatitis.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une composition pharmaceutique sous la forme d'un onguent pour le traitement de maladies dermatologiques, la composition comprenant du furoate de mométasone en tant que substance active et des adjuvants, comprend en outre des substances actives telles que du chlorhydrate de naftifine et de la mupirocine, ainsi que de l'hydroxystéarate de macrogolglycérol 40, de la vaseline liquide et de la vaseline en tant qu'adjuvants.
PCT/UA2020/000012 2019-03-19 2020-02-10 Composition pharmaceutique sous forme d'onguent pour le traitement de maladies dermatologiques WO2020190249A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
UAA201912337 2019-03-19
UAA201912337A UA124322C2 (uk) 2019-03-19 2019-03-19 Фармацевтична композиція у формі мазі для лікування дерматологічних захворювань

Publications (1)

Publication Number Publication Date
WO2020190249A1 true WO2020190249A1 (fr) 2020-09-24

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PCT/UA2020/000012 WO2020190249A1 (fr) 2019-03-19 2020-02-10 Composition pharmaceutique sous forme d'onguent pour le traitement de maladies dermatologiques

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UA (1) UA124322C2 (fr)
WO (1) WO2020190249A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2325912C1 (ru) * 2006-09-06 2008-06-10 Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") Фармацевтическая композиция противовоспалительного и антимикробного действия в форме мази на гидрофобной основе для лечения кожных заболеваний (варианты)
WO2012083341A1 (fr) * 2010-12-20 2012-06-28 Le Andrew Tuan Anh Composition pour le traitement d'états pathologiques de la peau
UA107968C2 (uk) 2010-05-26 2015-03-10 Альміралль, С.А. Фармацевтичні композиції для місцевого застосування

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2325912C1 (ru) * 2006-09-06 2008-06-10 Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") Фармацевтическая композиция противовоспалительного и антимикробного действия в форме мази на гидрофобной основе для лечения кожных заболеваний (варианты)
UA107968C2 (uk) 2010-05-26 2015-03-10 Альміралль, С.А. Фармацевтичні композиції для місцевого застосування
WO2012083341A1 (fr) * 2010-12-20 2012-06-28 Le Andrew Tuan Anh Composition pour le traitement d'états pathologiques de la peau

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GLAXOSMITHKLINE: "BACTROBAN OINTMENT - Mupirocin (2%w/w)", 10 October 2013 (2013-10-10), pages 1 - 3, XP055688828, Retrieved from the Internet <URL:https://au.gsk.com/media/222809/bactroban_ointment_cmi_au_004_approved.pdf> [retrieved on 20200423] *
L.P. YAGOTSKA: "Ways of optimization of topical therapy of microbial eczem", DERMATOLOHIYA TA VENEROLOHIYA - DERMATOLOGY AND VENEREOLOGY, vol. 84, no. 2, 2019, pages 65 - 67, XP000952088, Retrieved from the Internet <URL:http://idvamnu.com.ua/wp-content/uploads/2019/07/%D1%8F%D0%B3%D0%BE%D1%86%D0%BA%D0%B0%D1%8F.pdf> [retrieved on 20200422] *
MERCK & CO: "Patient Information ELOCON (El-oh-con) (mometasone furoate) ointment, 0.1%", 1 May 2018 (2018-05-01), pages 1 - 2, XP055688862, Retrieved from the Internet <URL:https://www.merck.com/product/usa/pi_circulars/e/elocon_ointment/elocon_ointment_ppi.pdf> [retrieved on 20200423] *
UNKNOWN: "NAFTIN -naftifine hydrochloride gel", 1 January 2018 (2018-01-01), pages 1 - 16, XP055688860, Retrieved from the Internet <URL:https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf> [retrieved on 20200423] *

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