TR201602760A1

TR201602760A1 - TOPICAL THERAPEUTIC FORMULATIONS

Info

Publication number: TR201602760A1
Application number: TR2016/02760A
Authority: TR
Inventors: Karaağaç Esra
Original assignee: Esra Karaagac
Priority date: 2016-03-03
Filing date: 2016-03-03
Publication date: 2017-09-21

Abstract

Mevcut buluş; akne, akne vulgaris, inflamatuar lezyonların eşlik ettiği hafif ve orta şiddetli akne vulgaris, cilt ve yumuşak doku enfeksiyonlarının semptomatik ve/veya terapötik tedavisinde kullanılmak üzere, linkozamid grubundaki antibiyotik özellikteki uygun etken madde ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek başına kullanıldığı veya bu etken maddenin diğer uygun aktif ajan/lar ile kombine tedavi olarak kullanıldığı farmasötik bileşim/ler ile ilgilidir.The present invention includes; For use in the symptomatic and / or therapeutic treatment of mild and moderate acne vulgaris, skin and soft tissue infections accompanied by acne, acne vulgaris, inflammatory lesions, the appropriate active ingredient and / or pharmaceutically acceptable derivatives of the linkozamide group are used as monotherapy for monotherapy. or a pharmaceutical composition (s) wherein this active ingredient is used as a combination therapy with other suitable active agent (s).

Description

TARIFNAME TOPIKAL TERAPÖTIK FORMÜLASYONLAR BULUSUN ILGILI OLDUGU ALAN Mevcut bulus; akne, akne vulgaris, inflamatuar lezyonlarin eslik ettigi hafif ve orta siddetli akne vulgaris, cilt ve yumusak doku enfeksiyonlarinin semptomatik ve/veya terapötik tedavisinde kullanilmak üzere, liiikozamid grubundaki antibiyotik özellikteki uygun etken madde ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farmasötik bilesim/ler ile ilgilidir. DESCRIPTION TOPICAL THERAPEUTIC FORMULATIONS FIELD OF THE INVENTION The present invention; acne, acne vulgaris, mild to moderate severity accompanied by inflammatory lesions symptomatic and/or therapeutic treatment of acne vulgaris, skin and soft tissue infections. suitable agent with antibiotic properties in the liicosamide group to be used in the treatment of substance and/or pharmaceutically acceptable derivatives alone as monotherapy used or as a combined treatment of this active ingredient with other suitable active agent/s relates to the pharmaceutical composition(s) for which it is used.

Mevcut bulus; linkozamid grubundaki antibiyotik özellikteki etken madde Klindamisin, metil7-kloro-6,7,8-trideoksi-6- {[(4R)- 1 -metil-4-propil-L-prolil]amino} - 1 -tiyo-L-treo-or-D- galakto-oktopiranosid (Formül I) ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan] lar ile kombinasyon olarak kullanildigi farmasötik bilesim/ ler ile ilgilidir. The present invention; Clindamycin, the antibiotic active ingredient in the lincosamide group, methyl7-chloro-6,7,8-trideoxy-6- {[(4R)-1-methyl-4-propyl-L-prolyl]amino}-1-thio-L-threo-or-D- galacto-octopyranoside (Formula I) and/or its pharmaceutically acceptable derivatives when this active substance is used alone as monotherapy or other suitable active relates to pharmaceutical composition(s) where it is used in combination with agents].

Formül 1: CH3`S ci HO\J±;Es7\î/l\CH3 Ayrica bulus, Klindamisin ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi fannasötik bilesimlerin topikal uygulama için uygun olan formülasyonlarini ve semptomatik ve/veya terapötik kullanimlarini da kapsamaktadir. ÖNCEKI TEKNIK (TEKNIGIN BILINEN DURUMU) Akne saç köklerinin yag ve ölü deri hücreleri ile gömülmesi sonucu olusan bir cilt hastaligidir. Akne lezyonlari yavas iyilesir ve bir lezyon iyilestiginde digeri ortaya çikabilir. Akne genellikle fonksiyonel yag bezlerinin en fazla sayida oldugu yüz, boyun, gögüs, sirt ve omuzlarda görünür.Formula 1: CH3`S ci HO\J±;Es7\i/1\CH3 In addition, the invention includes the use of Clindamycin and/or its pharmaceutically acceptable derivatives. when this active substance is used alone as monotherapy or other suitable active Topical application of pharmaceutical compositions used as combination therapy with agent/s formulations suitable for use and their symptomatic and/or therapeutic use. covers. PRIOR ART (KNOWN STATE OF THE ART) Acne is a skin condition that results from the embedding of hair follicles with oil and dead skin cells. is the disease. Acne lesions heal slowly, and when one lesion heals, another appears. it may come off. Acne is usually found on the face, neck, and sebaceous glands where the functional sebaceous glands are the most. appears on the chest, back, and shoulders.

Akne asagidaki sekillerde olabilir: l-Enflamatuar olmayan lezyonlar: Komedon (beyaz nokta ve siyah nokta): Kil foliküllerinin açikliklari, yag salgilari, ölü deri hücreleri ve bazen bakterilerle tikanabilir. Komedonlar Cilt yüzeyine açiliyorsa koyu renkte göründükleri için siyah nokta olarak adlandirilir. Komedonlar kapali oldugunda cilt yüzeyinden hafif kabariktir ve deri rengindedir, bunlar beyaz nokta olarak adlandirilir.Acne can take the following forms: l-Non-inflammatory lesions: Comedones (whiteheads and blackheads): openings of clay follicles, oil secretions, dead skin cells and sometimes bacteria. Comedones are dark in color if they open to the skin surface. They are called black dots because they appear. When the comedones are closed, the skin slightly raised from the surface and skin-colored, these are called white dots.

Z-Enflamatuar lezyonlar: Papüller: Cilt üzerinde enfeksiyonu ve iltihaplanmayi gösteren küçük çikintilardir. Z-Inflammatory lesions: Papules: Small protrusions on the skin that indicate infection and inflammation.

Papüller kirmizi ve hassas olabilir.Papules may be red and tender.

Püsrül (sivilce): Ucunda beyaz irin olan kirmizi ve hassas çikintilardir. Pustules (pimples): These are red and sensitive protrusions with white pus at the tip.

Nodüller: Cilt yüzeyinin altinda olusan, büyük, sert ve agrili topaklardir. Kil köklerinde, derin dokuda salgilarm birikmesi sonucu olusur. Nodules: They are large, hard and painful lumps that form under the skin surface. in clay roots, It occurs as a result of the accumulation of secretions in the deep tissue.

Kistler: Cilt yüzeyinin altinda agrili, irin dolu topaklardir. Bu çiban tarzi lezyonlar yara izi birakabilir. Cysts: Painful, pus-filled lumps under the surface of the skin. These boil-like lesions are scars it can leave.

Akne tedavisinde dört amaç vardir: l-Sebum üretimini azaltmak 2-Hüere yenilenmesini hizlandirmak 3-Bakteriyel enfeksiyonla mücadele 4-Ciltteki inflamasyonun azaltilmasi Klindamisin, aknedeki bakterilere karsi etkinligi olan bir antibiyotiktir. Akne tedavisinde topikal olarak kullanilan klindamisinün duyarli organizmalara karsi antibakteriyel etki gösterdigine inanilmaktadir. Klindamisin lipaz üreten mikroorganizmalari da inhibe eder.There are four goals in acne treatment: l-Reducing sebum production 2-Accelerating cell regeneration 3- Fight against bacterial infection 4-Reducing inflammation in the skin Clindamycin is an antibiotic with activity against bacteria in acne. acne treatment antibacterial effect of topically used clindamycin against susceptible organisms It is believed to show. Clindamycin also inhibits lipase-producing microorganisms.

Böylece aknede görülen entlamatuvar lezyonlarin olasi nedenlerinden biri olarak kabul edilen sebumdaki serbest yag asidi konsantrasyonunu düsürür. Thus, it is accepted as one of the possible causes of inflammatory lesions in acne. It reduces the free fatty acid concentration in the sebum.

Benzoil peroksit hafiften orta siddete kadar akne olgularinin tedavisinde kullanilir, komedonlarin azaltilmasinda etkilidir. Hafif keratolitik etkisi de vardir. Benzoil peroksit antibakteriyel etki gösterir. Antibakteriyel etkisi özellikle yagli folikül ve komedonlarda dominant mikroorganizma olarak bulunan Propionibacterium acnes'e karsi daha fazladir.Benzoyl peroxide is used in the treatment of mild to moderate acne cases, It is effective in reducing comedones. It also has a mild keratolytic effect. Benzoyl peroxide shows antibacterial effect. Its antibacterial effect is especially in oily follicles and comedones. It is more common against Propionibacterium acnes, which is the dominant microorganism.

Asiri sebumun uzaklastirilmasini saglayan kurutucu, hafif deskuamasyon yapici ve keratolitik etki de gösterir. A drier, mild desquamator, and It also shows keratolytic effect.

EP2049068 no”lu patent dökümaninda retinoid, antibiyotik ve/veya keratolitik özellikteki topikal antiakne formülasyonlardan bahsedilmektedir. In the patent document numbered EP2049068, it has retinoid, antibiotic and/or keratolytic properties. topical antiacne formulations are mentioned.

US6l 17843 n0”lu patent dökümaninda klindainisin ile benzoil peroksit içeren topikal jel formülasyonundan bahsedilmektedir.Topical gel containing clindainicin and benzoyl peroxide in patent document US61 17843 formulation is mentioned.

BULUSUN AÇIKLAMASI Mevcut bulus; akne, akne vulgaris, inflamatuar lezyonlarin eslik ettigi hafif ve orta siddetli akne vulgaris, cilt ve yumusak doku enfeksiyonlarinin seinptomatik ve/veya terapötik tedavisinde kullanilmak üzere, linkozamid grubundaki antibiyotik özellikteki uygun etken madde ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farmasötik bilesim/ ler ile ilgilidir. DESCRIPTION OF THE INVENTION The present invention; acne, acne vulgaris, mild to moderate severity accompanied by inflammatory lesions symptomatic and/or therapeutic treatment of acne vulgaris, skin and soft tissue infections. suitable agent with antibiotic properties in the lincosamide group to be used in the treatment of substance and/or pharmaceutically acceptable derivatives alone as monotherapy used or as a combined treatment of this active ingredient with other suitable active agent/s relates to the pharmaceutical composition(s) for which it is used.

Mevcut bulusun bir diger yönü; linkozamid grubundaki antibiyotik özellikteki uygun etken madde ve/veya farrnasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farmasötik bilesim/lerin tedavisini içeren farmasötik bilesim/lerin Bulusta kullanilan linkozamid grubundaki antibiyotik özellikteki uygun etken madde eritromisin, kloramfenikol, linkomisin, meklosiklin, klindamisin ve/veya farmasötik olarak kabul edilebilir türevleri arasindan tercihen klindamisin fosfat olarak seçilir. Another aspect of the present invention is; suitable agent with antibiotic properties in the lincosamide group substance and/or pharmaceutically acceptable derivatives alone as monotherapy used or as a combined treatment of this active ingredient with other suitable active agent/s pharmaceutical composition(s) containing the treatment of the pharmaceutical composition(s) for which it is used. Appropriate active substance with antibiotic properties in the lincosamide group used in the invention as erythromycin, chloramphenicol, lincomycin, meclocycline, clindamycin and/or pharmaceutical clindamycin phosphate is preferably selected from among its acceptable derivatives.

Bulusta kullanilan diger uygun aktif ajan/lar; antibakteriyel özellikteki benzoil peroksit ve azelaik asit arasindan tercihen benzoil peroksit olarak seçilir. Other suitable active agent(s) used in the invention; antibacterial benzoyl peroxide and Azelaic acid is preferably selected as benzoyl peroxide.

Bulusta “farrnasötik olarak kabul edilebilir türevleri” terimi ile farmasötik olarak kabul edilebilir uygun tuzlar, esterler, solvatlar, hidratlar, kompleksler, polimorflar, enantiyomerler, önilaçlar, asit adisyon tuzlari, analoglar, izomerler, rasematlar, amidler, enantiyomer tuzlari, bazik tuzlar, konjugeler, tautomerler, anhidratlar, anhidritler, bazlar, asitler, eterler, kristal ve ainorf formlar veya serbest formlarindan bir veya daha fazlasi ifade edilmektedir.The term "pharmaceutically acceptable derivatives" in the invention Suitable salts, esters, solvates, hydrates, complexes, polymorphs, enantiomers, prodrugs, acid addition salts, analogs, isomers, racemates, amides, enantiomer salts, basic salts, conjugates, tautomers, anhydrates, anhydrides, bases, one or more of acids, ethers, crystalline and amorphous forms or free forms is expressed.

Topikal uygulama için hazirlanan farmasötik bilesimler krem, jel, inerhein, losyon, liniinent (sivi merhem), süspansiyon, emülsiyon (su/yag, yag/su ), sivi çözelti, yaglar, macun, köpük, solüsyon, pat, stik, sprey, sabun, sampuan, pudra, supozituar ve enema gibi dozaj formlarinda olabilir. Pharmaceutical compositions prepared for topical application include cream, gel, inerhein, lotion, liniinent (liquid ointment), suspension, emulsion (water/oil, oil/water), liquid solution, oils, such as paste, foam, solution, paste, stick, spray, soap, shampoo, powder, suppository and enema. available in dosage forms.

Jeller, küçük anorganik partiküllerin süspansiyonu veya sivi ile sismis büyük makromoleküllerden olusan yari kati sistemlerdir.Ufak anorganik partiküller jel yapisi içinde üç boyutlu sebeke olustururlar. Dogal ve sentetik polimerler olan büyük anorganik makromoleküller ise birbirlerinin zinciri ile temasta olarak jel yapisini olusturur. Jeller de etkin maddelerin deriye uygulanmasi için, merhemler gibi tasiyici/sivag olarak kullanilabilirler. Jeller küçük kati madde veya çözünmeyen parçaciklarinin sivi ortamda dagilmasi ile olusmuslardir. Gels are suspensions of small inorganic particles or large swelled with liquid. They are semi-solid systems consisting of macromolecules. Small inorganic particles gel structure They form a three-dimensional network inside. Large inorganic polymers, natural and synthetic On the other hand, macromolecules form the gel structure in contact with each other's chain. Gels too as a carrier/sivag, such as ointments, for the application of active ingredients to the skin they can be used. Gels are composed of small solids or insoluble particles in a liquid medium. they were formed by the dispersion.

Jel olusturmak üzere pek çok degisik madde kullanilir. Bunlar: Jel yapici maddeler; l-Proteinler: Kollajen, jelatin 2-P01isakkarltler: Aljinatlar, agar, Karragen, Kitozan, Glisirizin 3-Yari sentetik polimerler: Sodyum karboksimetilselüioz (Na~CMC), Metil selüloz (MC), Hidroksipropilselüloz (HPC) ve Hidroksipropilmetilselüloz (HPMC) 4-Sentetik poliinerler: PoliVinil alkol (PVA), Poliakrilik asit kopolimerleri (CarbopoP Karbomer), Poliakrilamitler, Poloksamerler Mevcut bulusta topikal uygulama için hazirlanan farmasötik forrnülasyon; farmasötik olarak kabul edilebilir uygun etken maddeler yaninda en az bir baglayici madde, en az bir glidant, en az bir yumusatici madde, en az bir kivam arttirici madde, en az bir selat yapici ajan, en az bir emülgatör, en az bir jel yapici ajan, en az bir pH ayarlayici ajan, en az bir serinletici ajan, en az bir penetrasyon arttirici ajan, en az bir mikrobiyal koruyucu madde ve çözücünün de dahil oldugu gruptan seçilen bir veya daha fazla yardiinci madde içerebilen bir bilesimi tanimlar. Many different substances are used to form gels. These: Gel-forming agents; l-Proteins: Collagen, gelatin 2-P01isaccharides: Alginates, agar, Carrageen, Chitosan, Glycyrrhizin 3-Semi-synthetic polymers: Sodium carboxymethylcellulose (Na~CMC), Methyl cellulose (MC), Hydroxypropylcellulose (HPC) and Hydroxypropylmethylcellulose (HPMC) 4-Synthetic polyiners: PolyVinyl alcohol (PVA), Polyacrylic acid copolymers (CarbopoP Carbomer), Polyacrylamides, Poloxamers The pharmaceutical formulation prepared for topical application in the present invention; pharmaceutical at least one binding agent, at least one glidant, at least one softening agent, at least one thickening agent, at least one chelating agent agent, at least one emulsifier, at least one gelling agent, at least one pH adjusting agent, at least one cooling agent, at least one penetration enhancing agent, at least one microbial preservative and one or more excipients selected from the group consisting of solvent Defines a composition that can contain

Bulusta “baglayici madde” olarak prejelatinize misir nisastasi, prejelatinize nisasta, hidroksi propil nisasta, jelatin, mikrokristalin selüloz, selüloz, zamklar, polivinil pirolidon, polimetakrilatlar, sodyum karboksi metil selüloz, nisasta, parafinler, stearik asit, zamklar, metil selüloz, etil selüloz, polietilenglikol, magnezyum alüminyum silikat, karboksi metilselüloz, hidroksi propilselüloz, hidroksi etilselüloz, propilen glikol, polioksietilen- polipropilen kopolimeri, polietilen ester, polietilen sorbitaii ester, polietilen oksit, polisakkaritler, poloksamerler, aljinik asitler, kolajen, albumin, krospovidon, povidon, kopovidon, maltodekstrin, hipromelloz veya bunlarin karisimlari kullanilabilir. In the invention, pregelatinized corn starch, pregelatinized starch, hydroxypropyl starch, gelatin, microcrystalline cellulose, cellulose, gums, polyvinyl pyrrolidone, polymethacrylates, sodium carboxymethyl cellulose, starch, paraffins, stearic acid, gums, methyl cellulose, ethyl cellulose, polyethyleneglycol, magnesium aluminum silicate, carboxy methylcellulose, hydroxy propylcellulose, hydroxy ethylcellulose, propylene glycol, polyoxyethylene- polypropylene copolymer, polyethylene ester, polyethylene sorbitaii ester, polyethylene oxide, polysaccharides, poloxamers, alginic acids, collagen, albumin, crospovidone, povidone, Copovidone, maltodextrin, hypromellose or mixtures of these can be used.

Bulusta “glidant” olarak talk, magnezyum stearat, hidrojene nebati yag, kalsiyum stearat, stearik asit, kolloidal silikon dioksit, sodyum stearilfumarat, polioksietilenglikol, lösin, sodyum benzoat, sodyum klorür, sodyum asetat, sodyum fumarat, silika, kolloidal anhidrus silika, kolloidal sulu formda silika, polietilenglikol, selüloz türevleri, nisasta veya bunlarin karisimlari kullanilabilir. In the invention, talc, magnesium stearate, hydrogenated vegetable oil, calcium stearate, stearic acid, colloidal silicon dioxide, sodium stearylfumate, polyoxyethyleneglycol, leucine, sodium benzoate, sodium chloride, sodium acetate, sodium fumarate, silica, colloidal anhydrous silica, colloidal silica in aqueous form, polyethyleneglycol, cellulose derivatives, starch or their mixes can be used.

Bulusta “yumusatici madde” terimi; cilt üzerinde ince bir film tabakasi olusturarak suyun uçmasina engel olan maddeler olarak ifade edilmektedir. Yumusatici madde olarak vazelin, kati vazelin, sivi parafin, sorbitol, gliserin, hidrokarbonlar, lanolin, mumlar, yag asitleri, setil alkol, oktildodekanol, kaprilik/ kaprik trigliserit, setil stearil alkol, kakao yagi, diizopropil adipat, polihidrik alkoller ve polieter türevleri, polihidrik alkol esterleri, gliseril monooleat, gliseril stearat, liiioleik asit, oleik asit, polipropilen glikOl-lS stearil eter (PPG- stearil eter), polietilen glikol, polioksietilen glikol yagli alkol eterleri, polioksipropilen stearil eter, propilen glikol stearat, stearik asit, stearil alkol, fosfolipidler, lesitin, steoroller, kolesterol, kolesterol yag asidi esterleri ve amidleri, üre, gliseril inonostearat, isopropil miristat, isopropil palmitat, ketostearil alkol, diinetikon, mineral yaglar, beyaz kati parafin, setearil alkol veya bunlarin karisimlari kullanilabilir. Ayrica hint yagi, Hindistan cevizi yagi, zeytinyagi ve bitkisel mumlar gibi bitkisel yumusatici ajanlar da kullanilabilir. The term "softening agent" in the invention; water by forming a thin film on the skin It is expressed as substances that prevent it from flying. Vaseline as an emollient, solid petrolatum, liquid paraffin, sorbitol, glycerin, hydrocarbons, lanolin, waxes, fatty acids, cetyl alcohol, octyldodecanol, caprylic/capric triglyceride, cetyl stearyl alcohol, cocoa butter, diisopropyl adipate, polyhydric alcohols and polyether derivatives, polyhydric alcohol esters, glyceryl monooleate, glyceryl stearate, liioleic acid, oleic acid, polypropylene glycol-1S stearyl ether (PPG- stearyl ether), polyethylene glycol, polyoxyethylene glycol fatty alcohol ethers, polyoxypropylene stearyl ether, propylene glycol stearate, stearic acid, stearyl alcohol, phospholipids, lecithin, steorols, cholesterol, cholesterol fatty acid esters and amides, urea, glyceryl inonostearate, isopropyl myristate, isopropyl palmitate, ketostearyl alcohol, diinethicone, mineral oils, white solid paraffin, cetearyl alcohol or mixtures thereof can be used. Also castor oil, coconut Vegetable softening agents such as oil, olive oil and vegetable waxes can also be used.

Bulusta “kivam arttirici madde” olarak; setil alkol, alüminyum stearat, dimetikon, setearil alkol, stearil alkol, arap zamki, kitre zamki, aljinat, karragen, ksantan zamki, guar zamki, setostearil alkol, seti] esterlerin mumu, dekstrin, gliseril moiiostearat, hidroksipropil selüloz, kaolin, polietilen beyaz vazelin, propilen glikol stearat, nisasta, mum, beyaz mum, bentonit, balmumu, beyaz balmumu, sentetik balmumu, parafin, beyaz kati parafin, beyaz yumusak parafin, kati vazelin, pektin, karbomer, poliviiiilprolidon veya bunlarin karisimlari kullanilabilir. As "thickening agent" in the invention; cetyl alcohol, aluminum stearate, dimethicone, cetearyl alcohol, stearyl alcohol, gum arabic, gum tragacanth, alginate, carrageenan, xanthan gum, guar gum, cetostearyl alcohol, cete] wax of esters, dextrin, glyceryl moiostearate, hydroxypropyl cellulose, kaolin, polyethylene white vaseline, propylene glycol stearate, starch, wax, white wax, bentonite, beeswax, white wax, synthetic wax, paraffin, white solid paraffin, white soft paraffin, solid petrolatum, pectin, carbomer, polyvinylprolidone or their mixes can be used.

Bulusta selat yapici ajan olarak EDTA (etilen diamin tetraasetik asit), disodyum EDTA (disodyum etilen diainin tetraasetik asit) veya kalsiyum EDTA (kalsiyum etileii diamin tetraasetik asit) veya buiilarin karisimlari kullanilabilir. EDTA (ethylene diamine tetraacetic acid), disodium EDTA as chelating agent in the invention (disodium ethylene diamine tetraacetic acid) or calcium EDTA (calcium ethylene diamine tetraacetic acid) or mixtures of these can be used.

Bulusta “emülgatör” terimi, birbiri içerisinde karismayan iki sivi faz arasinda homojen dagilimi saglayan maddeler olarak ifade edilmektedir. Emülgatör olarak polietilen glikol stearat, polisorbat, poligliseril oleat, polioksietilen lauril eter, etoksillenmis lanolin, stearil alkol, setostearil alkol, inakrogol setostearil, gliseril monostearat, setil alkol, polioksietilen lauril alkol, polioksi etilen sorbitan monostearat, polioksietilen stearat, sorbitan monostearat, propilen glikol stearat, alüminyum nisasta oktenilsuksinat, amonyum hidroksit, beyaz bir balmumu, sentetik bir balmumu, karbomer, setearil alkol, siklometikon, digliseritler, dimetikon, disodyuin monooleamido sülfosüksinat, pentaeritritol, gliseritler, gliseril monooleat, gliseril stearat, lanolin, magnezyum hidrojene stearat, mineral yag, monogliseridler, polietilen glikol, polietilen glikol distearat, polietilen glikol monosetil eter, polietilen glikol monostearat, polioksietilen glikol, polioksil setostearil eter, polioksil stearat, simetikon, sorbitan monolaurat, sorbitan moiiooleat, sorbitan monopalmitat, sorbitan palmitat, stearik asit, disodyum lauril sülfosüksinat, trietanolamin, sodyum lauril sülfat veya bunlarin karisimlari kullanilabilir. In the invention, the term "emulsifier" means homogeneous between two immiscible liquid phases. are expressed as substances that provide dispersion. Polyethylene glycol as emulsifier stearate, polysorbate, polyglyceryl oleate, polyoxyethylene lauryl ether, ethoxylated lanolin, stearyl alcohol, cetostearyl alcohol, inacrogol cetostearyl, glyceryl monostearate, cetyl alcohol, polyoxyethylene lauryl alcohol, polyoxy ethylene sorbitan monostearate, polyoxyethylene stearate, sorbitan monostearate, propylene glycol stearate, aluminum starch octenylsuccinate, ammonium hydroxide, a white wax, a synthetic wax, carbomer, cetearyl alcohol, cyclomethicone, diglycerides, dimethicone, disodyuin monooleamido sulfosuccinate, pentaerythritol, glycerides, glyceryl monooleate, glyceryl stearate, lanolin, hydrogenated magnesium stearate, mineral oil, monoglycerides, polyethylene glycol, polyethylene glycol distearate, polyethylene glycol monocetyl ether, polyethylene glycol monostearate, polyoxyethylene glycol, polyoxyl cetostearyl ether, polyoxyl stearate, simethicone, sorbitan monolaurate, sorbitan moiiooleate, sorbitan monopalmitate, sorbitan palmitate, stearic acid, disodium lauryl sulfosuccinate, triethanolamine, sodium lauryl sulfate or mixtures thereof can be used.

Bulusta “jel yapici ajan” olarak karbopol, karbomer, hidroksi propilmetilselüloz, metilselüloz, hidroksi etilselüloz, hidroksi propilselüloz, karboksi metilhidroksi etilselüloz, sodyum karboksi metilselüloz, metoksipolietilenglikol, polietilenglikol, benzil alkol, etil alkol, izopropil alkol, hyaluronik asit, karboksivinil poliinerler, poliakrilat poliinerleri, polietilen glikol ketostearil eter veya bunlarin karisimlari kullanilabilir. In the invention, carbopol, carbomer, hydroxy propylmethylcellulose, methylcellulose, hydroxy ethylcellulose, hydroxy propylcellulose, carboxy methylhydroxy ethylcellulose, sodium carboxy methylcellulose, methoxypolyethyleneglycol, polyethyleneglycol, benzyl alcohol, ethyl alcohol, isopropyl alcohol, hyaluronic acid, carboxyvinyl polyiners, polyacrylate polyiners, polyethylene glycol ketostearyl ether or mixtures thereof may be used.

Bulusta “pH ayarlayici ajan” terimi, kompozisyonun asitlik ve bazligini düzenleyen maddeler olarak ifade edilmektedir. pH ayarlayici ajan olarak; sitrik asit anhidrus, sodyum sitrat dihidrat, sodyum fosfat, sodyum dihidrojen fosfat, potasyum sitrat, fosforik asit, amonyum hidroksit, sitrik asit, diizopropanolamin, sodyum karbonat, sodyum silikat, disodyum ortofosfat, kalsiyum karbonat, magnezyum karbonat, magnezyum hidroksit, magnezyum alüminat, dietanol ainin, sodyum aljinat, etilendiamin, meglümin, hidroklorik asit, laktik asit, sodyum sitrat, sodyum bikarbonat, sodyum hidroksit, sodyum klorür, dietanolamin, dietilamin, trietanolainin, trolainine, trometamin, sodyum benzoat, sodyum hidrojen karbonat veya bunlarin karisimlari kullanilabilir. In the invention, the term "pH adjusting agent" is used to regulate the acidity and basicity of the composition. referred to as items. As a pH adjusting agent; citric acid anhydrous, sodium citrate dihydrate, sodium phosphate, sodium dihydrogen phosphate, potassium citrate, phosphoric acid, ammonium hydroxide, citric acid, diisopropanolamine, sodium carbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium aluminate, diethanol aine, sodium alginate, ethylenediamine, meglumine, hydrochloric acid, lactic acid, sodium citrate, sodium bicarbonate, sodium hydroxide, sodium chloride, diethanolamine, diethylamine, triethanolamine, trolainine, tromethamine, sodium benzoate, sodium hydrogen carbonate or mixtures thereof can be used.

Bulusta “serinletici ajan” olarak mentol esterleri, mentil, mentol kristali, ökaliptol, sentetik veya dogal levomentol veya bunlarin karisimlari kullanilabilir. Menthol esters, menthylene, menthol crystal, eucalyptol, synthetic or natural levomenthol or their mixtures can be used.

Bulusta “penetrasyon arttirici ajan” terimi; maddelerin deriden veya biyolojik membranlardan daha iyi ve yüksek derecede penetre olmasini saglayan kimyasal bilesimler olarak ifade edilmektedir. Penetrasyon arttirici ajan olarak polipropilen glikol-15 stearil eter, dimetil sülfoksit, pirolidonlar, azon, propilen glikol, yag asitleri, terpenler, terpenoidler, oksazolidinonlar, üreler, isopropil miristat, linoleat, palmitat, palmitat stearat veya bunlarin karisimlari kullanilabilir. The term "penetration enhancing agent" in the invention; substances from the skin or biological chemical compositions that allow better and higher penetration through membranes is expressed as. Polypropylene glycol-15 stearyl as penetration enhancing agent ether, dimethyl sulfoxide, pyrrolidones, azone, propylene glycol, fatty acids, terpenes, terpenoids, oxazolidinones, ureas, isopropyl myristate, linoleate, palmitate, palmitate stearate or mixtures of these can be used.

Bulusta “mikrobiyal koruyucu madde” terimi mikrobiyal aktiviteye karsi koruyan maddeler olarak ifade edilmektedir. Mikrobiyal koruyucu madde olarak; sodyum benzoat, sodyum metil para hidroksibenzoat, sodyum propil para hidroksibenzoat, benzalkonyum klorit, borik asit, sorbik asit, etil alkol veya bunlarin karisimlari kullanilabilir. In the invention, the term "microbial preservative" protects against microbial activity. referred to as items. As a microbial preservative; sodium benzoate, sodium methyl para hydroxybenzoate, sodium propyl para hydroxybenzoate, benzalkonium chloride, boric acid, sorbic acid, ethyl alcohol or their mixtures can be used.

Bulusta çözücü olarak saf su, etil alkol, metil alkol, isopropil alkol, butil alkol gibi alkoller, aseton, diaseton, polioller, polieterler, esterler, alkil ketonlar, metilen klorür, metil asetat, etil asetat, izopropil asetat, etilen glikol monoetil eter, dietilen glikol monobutil eter, dietilen glikol monoetil eter veya bunlarin karisimlari kullanilabilir. In the invention, alcohols such as pure water, ethyl alcohol, methyl alcohol, isopropyl alcohol, butyl alcohol as solvents, acetone, diacetone, polyols, polyethers, esters, alkyl ketones, methylene chloride, methyl acetate, ethyl acetate, isopropyl acetate, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether or mixtures thereof may be used.

Bulus esas olarak, topikal kullanilmak üzere linkozamid grubundaki antibiyotik özellikteki klindainisin ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin antibakteriyel özellikteki benzoil peroksit ile kombine tedavi olarak kullanildigi farmasötik bilesim/ler ile ilgilidir. Bulusun farmasötik bilesim/lerinin jel formunda olmasi temeldir. Söz konusu farmasötik formülasyonlarm uygun pH”larda hazirlanmasiyla emilimin ve biyouyumlulugun arttigi sasirtici sekilde gözlenmistir. Söz konusu jel formu ile stabil, raf ömrü uzun, yüksek saglamlikli, olumlu reolojik ve tiksotropik özellikli, kolay kullanimli, yardimci maddelerle uyumlu, güvenilir ve etkinligi yüksek farmasötik bilesimler elde edilmistir.The invention is mainly used as an antibiotic in the lincosamide group for topical use. clindainicin and/or its pharmaceutically acceptable derivatives as monotherapy alone used on its own or with the antibacterial benzoyl peroxide of this active ingredient. relates to the pharmaceutical composition(s) used as a combination therapy. Invention pharmaceutical It is essential that the composition(s) be in gel form. These pharmaceutical formulations Surprisingly, absorption and biocompatibility increase with preparation at appropriate pH's. has been observed. With the gel form in question, it is stable, has a long shelf life, has high strength, rheological and thixotropic, easy to use, compatible with auxiliary substances, reliable and high efficacy pharmaceutical compositions were obtained.

Claims

ISTEMLER . Topikal kullanilmak üzere linkozamid grubundaki antibiyotik özellikteki uygun etken madde ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farmasötik bilesim/lerin hazirlanmasi. . Istem l°deki gibi farmasötik bilesim/ler olup özelligi; linkozamid grubundaki antibiyotik özellikteki uygun etken maddenin eritromisin, kloramfenikol, linkomisin, meklosiklin, klindamisin ve/Veya farmasötik olarak kabul edilebilir türevleri arasindan seçilmesidir. . Istein 2”deki gibi farmasötik bilesim/ler olup özelligi; linkozainid grubundaki antibiyotik özellikteki uygun etken maddenin tercihen klindamisin fosfat olmasidir. . Istem l”deki gibi farmasötik bilesim/ler olup özelligi; kullanilan diger uygun aktif ajan/larin; antibakteriyel özellikteki benzoil peroksit ve azelaik asit arasindan seçilmesidir. . Istem 4”deki gibi farmasötik bilesim/ler olup özelligi; kullanilan diger uygun aktif` ajan/larin tercihen antibakteriyel özellikteki benzoil peroksit olmasidir. . Istein l°deki gibi farmasötik bilesim/ler olup özelligi; krem, jel, merhem, losyon, liniment (sivi merhem), süspansiyon, emülsiyon (su/yag, yag/su ), sivi çözelti, yaglar, macun, köpük, solüsyon, pat, stik, sprey, sabun, sampuan, pudra, supozituar ve enema arasindan seçilen bir veya daha fazla farmasötik dozaj formunu içermesidir. . Istem 67daki gibi farmasötik bilesim/ler olup özelligi; farmasötik dozaj formunun tercihen jel olmasidir. . Yukaridaki istemlerden herhangi birine göre farmasötik bilesim/ler olup özelligi; akne, akne vulgaris, inflamatuar lezyonlarin eslik ettigi hatif ve orta siddetli akne vulgaris, cilt ve yumusak doku enfeksiyonlarinin semptomatik ve/veya terapötik tedavisinde endike olmasidir.REQUESTS . Preparation of pharmaceutical composition(s) for topical use, in which the appropriate active ingredient and/or pharmaceutically acceptable derivatives with antibiotic properties in the lincosamide group are used alone as monotherapy or in which this active ingredient is used in combination with other appropriate active agent/s. . It is a pharmaceutical composition/s as in claim 1 and its feature is; is to select the appropriate active ingredient with antibiotic properties in the lincosamide group among erythromycin, chloramphenicol, lincomycin, meclocycline, clindamycin and/or pharmaceutically acceptable derivatives. . It is a pharmaceutical composition/s as in Request 2 and its feature is; Preferably, clindamycin phosphate is the appropriate antibiotic agent in the lincosainide group. . It is a pharmaceutical composition/s as in claim 1 and its feature is; other suitable active agent(s) used; It is chosen among antibacterial benzoyl peroxide and azelaic acid. . It is a pharmaceutical composition/s as in Claim 4 and its feature is; Another suitable active agent/s used is preferably antibacterial benzoyl peroxide. . The request is pharmaceutical composition/s as in 1 and its feature is; cream, gel, ointment, lotion, liniment (liquid ointment), suspension, emulsion (water/oil, oil/water), liquid solution, oils, paste, foam, solution, paste, stick, spray, soap, shampoo, powder, comprising one or more pharmaceutical dosage forms selected from suppository and enema. . It is pharmaceutical composition/s as in Claim 67 and its feature is; preferably the pharmaceutical dosage form is gel. . It is a pharmaceutical composition/s according to any of the above claims and its feature is; It is indicated for the symptomatic and/or therapeutic treatment of acne, acne vulgaris, mild to moderate acne vulgaris accompanied by inflammatory lesions, skin and soft tissue infections.