TR2021021396A1 - INHIBITORY EFFECTS OF CHLOROGENIC ACID ON COX-1, COX-2 AND LOX ENZYMES - Google Patents

INHIBITORY EFFECTS OF CHLOROGENIC ACID ON COX-1, COX-2 AND LOX ENZYMES

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Publication number
TR2021021396A1
TR2021021396A1 TR2021/021396 TR2021021396A1 TR 2021021396 A1 TR2021021396 A1 TR 2021021396A1 TR 2021/021396 TR2021/021396 TR 2021/021396 TR 2021021396 A1 TR2021021396 A1 TR 2021021396A1
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TR
Turkey
Prior art keywords
chlorogenic acid
cox
inflammatory agent
inflammatory
inhibitory effects
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Application number
TR2021/021396
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Turkish (tr)
Inventor
E Esra Karada Ay
Nur Bi̇lteki̇n Kaleli̇ Sevde
Tosun Fatma
Original Assignee
İstanbul Medi̇pol Üni̇versi̇tesi̇
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Application filed by İstanbul Medi̇pol Üni̇versi̇tesi̇ filed Critical İstanbul Medi̇pol Üni̇versi̇tesi̇
Publication of TR2021021396A1 publication Critical patent/TR2021021396A1/en

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Abstract

Mevcut buluş, antienflamatuvar ajan olarak kullanım için klorojenik asit maddesi ile ve bu maddeyi içeren farmasötik bileşimlerle ilgilidir.The present invention relates to chlorogenic acid for use as an anti-inflammatory agent and to pharmaceutical compositions containing it.

Description

TARIFNAME KLOROJENIK ASITIN COX-l, COX-2 VE LOX ENZIMLERINI INHIBE EDICI ETKILERI Teknik Alan Mevcut bulus, antienflamatuvar ajan olarak kullanim için klorojenik asit maddesi ile ve bu maddeyi içeren farrnasötik bilesimlerle ilgilidir. Teknigin Bilinen Durumu Entlamasyon kaynakli rahatsizliklar siklikla karsimiza çikmaktadir. Vücudun farkli bölgelerinde farkli nedenlerle meydana gelen enflamasyonlarin tedavisi çesitli konvansiyonel ilaçlarla saglanmaya çalisilmaktadir. Ancak kullanilan bu ajanlarla tedavi zaman zaman yetersiz kalmakla beraber yeni ve dogal antienflamatuar aj anlarin kesfi büyük Önem tasimaktadir. Dogal kaynakli terapötik ajanlarin ticari kullaniminda en çok karsilasilan problemlerden biri dogal ürünlerden elde edilen ekstrelerin içerisindeki farmasötik etkiye sahip madde miktarinin sabit olmamasidir. Bitkinin toplandigi bölgeye veya toplandigi döneme göre degisiklik gösterebilen burn iktar degisikligi, bitkisel kökenli ekstreler kullanilarak etkinligi tekrar edilebilir ve standardize edilebilir formülasyonlar gelistirilmesini engellemektedir. Teknigin bilinen durumu göz önüne alindiginda hem bitkisel veya dogal kaynaklardan elde edilen hem de içerisinde bulunan farmasötik etkinlik gösteren madde miktari yönünden standardize edilebilen antienflamatuar ajanlara ihtiyaç oldugu görülmektedir. Bulusun Amaci Bulus sahipleri, bitkisel veya dogal kaynaklardan elde edilen ve içerisinde bulunan farmasötik etkinlik gösteren madde miktari yönünden standardize edilebilen antienilamatuar ajanlar gelistirmeyi amaçlamaktadir. Bulusun Kisa Açiklamasi Mevcut bulus antienflamatuvar ajan olarak kullanim için klorojenik asit maddesine veya herhangi bir oranda örnegin %0,I - %99 oraninda klorojenik asit içeren bilesiklere, tercihen %0,I - %99 oraninda klorojenik asit içeren bitki esktrelerine, özellikle tercihen %0,] ile "095 oraninda klorojenik asir içeren Taraxacum ogîci'nale toprak üstü kisimlarinin ekstresine, örnegin %O,1-%2 oraninda klorojenik asit içeren T araxaciim ofjîci'nale toprak üstü kisimlarinin ekstresine yöneliktir. Ayrica, COX ve LOX enzimlerini selektif olarak inhibe eden çok fazla ajan olmamasi nedeniyle, bulusa uygun antienilamatuvar ajan olarak kullanim için klorojenik asit ile hastalara dogal bir antientlamatuar ajan saglanmaktadir. Bulusun Detayli Anlatimi Bulusun bir uygulamasi antienflamatuvar ajan olarak kullanim için en az %95 saflikta klorojenik asite iliskindir. Bulusun tercih edilen bir uygulamasi antienflamatuar ajan olarak kullanim için % 95-99 saflikta kloroj enik asite iliskindir. Bulusun özellikle tercih edilen bir uygulamasi antienflamatuar ajan olarak kullanim için % 97-99 saflikta klorojenik asite iliskindir. Bulus kapsaminda bahsedilen % sailikta klorojenik asit miktari, standardize ajanin Türk Farmakopesi-II monograflar (Avrupa farmakopesi adaptasyonu) - 2016 isimli kaynakta (TC. Saglik Bakanligi, Türkiye Ilaç ve Tibbi cihaz kurumu, I. Baski, 2016) klorojenik asit tayininde kullanilan herhangi bir analiz yöntemi örnegin HPLC ve/veya HPTLC cihazi analizleri ile belirlenmektedir. Bu bulus kapsaminda bahsi geçen % orani relatif bir oran olup, analize tabi tutulan klorojenik asit numunesindeki toplam madde miktarina kiyasla klorojenik asit miktarini ifade etmektedir. Örnegin, bir klorojenik asit numunesinin HPLC analizinde elde edilen tüm pik alani 100 ile ifade edilecek olursa, bulusa uygun bir kloroj enik asit numunesinde klorojenik asit°e karsilik gelen pikin alani en az 95 olmalidir. Burada kullanilan antientlamatuar ajan ifadesi, COX-l ve/Veya COX-2 ve/veya LOX inhibitörü etkisi gösteren aj anlari da kapsamaktadir. Bulus bir diger açidan, antienflamatuvar ajan olarak kullanima uygun etken madde olarak en az Bulusun bir diger unsuru, etken madde olarak en az %95 saflikta, tercihen %95-99 satlikta, özellikle tercihen %97-99 saflikta klorojenik asit içeren farrnasötik bilesimlerde bahsi geçen bu etken maddeye ilave olarak bir diger antienflamatuar ajan kullanilmasidir. Bulusun bir uygulamasinda bahsi geçen ilave antienflamatuar ajan ibuprofen veya diklofenak olabilir. Bulusa uygun kombinasyonlar, ayni dozaj formunda veya farkli dozaj fonnlarinda formüle edilebilir. Bulusa uygun kombinasyon forrnülasyonlarinin farkli dozaj formlarinda formüle edilmesi durumunda bahsi geçen forrnülasyonlar farkli zamanlarda veya ayni anda veya sirali olarak kullanilabilir. Bulusa uygun formülasyonlar oral veya topikal kullanima uygun bir dozaj formunda formüle edilebilir. Oral forrnülasyonlar, tablet, kapsül, uzun salinimli kapsül, geciktirilmis salinimli kapsül, surup, emülsiyon, süspansiyon, kaplamali tablet, katmanli tablet, agizda dagilan tablet, efervesan tablet, sase, dil alti tablet forrnlarindan herhangi birinde olabilir. Topikal forrnülasyonlar, merhem, krem, jel, hidrojel, losyon formlarindan herhangi birinde olabilir. Bulusa uygun formülasyonlar içerisinde klorojenik asite ek olarak fannasötik olarak kabul edilebilir en az bir yardimci madde olabilir. Bahsi geçen yardimci madde, herhangi bir terapötik etkisi olmayip, formülasyonun hazirlanmasi veya korunmasi veya kullanimi esnasinda ortaya çikan bir gereksinimi karsilamak için kullanilabilir. Endüstriye Uygulanabilirlik Bulus sayesinde antienflamatuar ajan olarak kullanima uygun dogal kökenli ajanlar gelistirilmistir. Bu yönüyle bulus hem saglik sektöründeki son kullanicilari hem de ilaç gelistiricilerini il gilendirmektedir. Örnekler Örnek 1: Bulusa uygun en az %95 safliga sahip klorojenik asit numunesinin COX-l ve COX-Z inhibisyonu için 1C50 degerleri ve bilinen antienflamatuar ajanlarla karsilastirilmasi Asagida sonuçlari verilen çalismada kullanilan klorojenik asit numunesi içerisinde % 95 klorojenik asit bulunmaktadir. Madde No. ICso (ug/mL) SI Örnek 17de yer alan sonuçlar degerlendirildiginde bulusa uygun en az %95 klorojenik asit içeren numunenin dogal bir madde olmasina ragmen ticari olarak uzun sürelerdir kullanilan diklofenak ve ibuprofen gibi antienflamatuvar ajanlardan daha iyi antienflamatuar etki gösterdigi görülmektedir. Burada görüldügü üzere, bulusa uygun dogal ajan diklofenak molekülüne kiyasla COX-l ve COK-2 inhibisyonu açisindan daha iyi etkinlik, bir diger deyisler. daha yüksek antienflamatuar etki, spesifik olarak COX-l ve COX-2 inhibitör etkisi göstermektedir. Tüm bu deney verileri bu dogal kaynakli standardize maddenin önemli bir antieflamatuar ajan olabilecegini ortaya koymaktadir. TR TR TR TR DESCRIPTION INHIBITORY EFFECTS OF CHLOROGENIC ACID ON COX-1, COX-2 AND LOX ENZYMES Technical Field The present invention relates to the substance chlorogenic acid for use as an anti-inflammatory agent and to pharmaceutical compositions containing this substance. Known Status of the Technique Disorders caused by entlamination occur frequently. Inflammations that occur in different parts of the body for different reasons are tried to be treated with various conventional drugs. However, although treatment with these agents is sometimes insufficient, the discovery of new and natural anti-inflammatory agents is of great importance. One of the most encountered problems in the commercial use of naturally derived therapeutic agents is that the amount of substances with pharmaceutical effects in the extracts obtained from natural products is not constant. Variation in nose quantity, which may vary depending on the region where the plant is collected or the period in which it is collected, prevents the development of reproducible and standardizable formulations using plant-derived extracts. Considering the known state of the art, it seems that there is a need for anti-inflammatory agents that are obtained from herbal or natural sources and can be standardized in terms of the amount of pharmaceutically active substances they contain. Purpose of the Invention The inventors aim to develop anti-inflammatory agents that are obtained from herbal or natural sources and can be standardized in terms of the amount of pharmaceutically active substances they contain. Brief Description of the Invention The present invention relates to chlorogenic acid for use as an anti-inflammatory agent or to compounds containing chlorogenic acid in any proportion, such as 0.1% to 99%, preferably plant extracts containing 0.1% to 99% chlorogenic acid, particularly preferably 0%. ,] is directed to the extract of aerial parts of Taraxacum ogîci'nale containing 0.95% of chlorogenic acid, for example, to the extract of aboveground parts of Taraxacum ofjîci'nale containing 0.1%-2% chlorogenic acid. In addition, it selectively inhibits COX and LOX enzymes. Since there are not many agents available, a natural anti-inflammatory agent is provided to patients with chlorogenic acid for use as an anti-inflammatory agent in accordance with the invention. Detailed Description of the Invention A preferred embodiment of the invention relates to chlorogenic acid with at least 95% purity for use as an anti-inflammatory agent. Relates to 95-99% purity chlorogenic acid for use as an agent. A particularly preferred embodiment of the invention relates to 97-99% pure chlorogenic acid for use as an anti-inflammatory agent. The % amount of chlorogenic acid mentioned within the scope of the invention does not correspond to any standard agent used in the determination of chlorogenic acid in the source named Turkish Pharmacopoeia-II monographs (European pharmacopoeia adaptation) - 2016 (Turkish Ministry of Health, Turkish Medicine and Medical Device Agency, I. Edition, 2016). The analysis method is determined, for example, by HPLC and/or HPTLC device analysis. Within the scope of this invention, the percentage mentioned is a relative ratio and expresses the amount of chlorogenic acid compared to the total amount of substance in the chlorogenic acid sample subjected to analysis. For example, if the entire peak area obtained in the HPLC analysis of a chlorogenic acid sample is expressed as 100, the area of the peak corresponding to chlorogenic acid in a chlorogenic acid sample according to the invention must be at least 95. The term anti-inflammatory agent used here also includes agents that have COX-1 and/or COX-2 and/or LOX inhibitory effects. In another aspect, the invention refers to the active ingredient suitable for use as an anti-inflammatory agent in pharmaceutical compositions containing at least 95% purity, preferably 95-99% purity, especially preferably 97-99% purity chlorogenic acid as the active ingredient. In addition to this active ingredient, another anti-inflammatory agent is used. In one embodiment of the invention, said additional anti-inflammatory agent may be ibuprofen or diclofenac. The combinations according to the invention can be formulated in the same dosage form or in different dosage forms. If the combination formulations according to the invention are formulated in different dosage forms, said formulations can be used at different times or simultaneously or sequentially. The formulations according to the invention can be formulated in a dosage form suitable for oral or topical use. Oral formulations can be in any of the forms of tablet, capsule, extended-release capsule, delayed-release capsule, syrup, emulsion, suspension, coated tablet, layered tablet, orodispersible tablet, effervescent tablet, sachet, or sublingual tablet. Topical formulations can be in any of the forms of ointment, cream, gel, hydrogel or lotion. In addition to the chlorogenic acid, the formulations according to the invention may contain at least one pharmaceutically acceptable excipient. Said excipient does not have any therapeutic effect and may be used to meet a need arising during the preparation or preservation of the formulation or during its use. Industrial Applicability Thanks to the invention, natural origin agents suitable for use as anti-inflammatory agents have been developed. In this respect, the invention interests both end users in the healthcare sector and drug developers. Examples Example 1: Comparison of 1C50 values for COX-1 and COX-Z inhibition and known anti-inflammatory agents of a chlorogenic acid sample with at least 95% purity in accordance with the invention. The chlorogenic acid sample used in the study whose results are given below contains 95% chlorogenic acid. Item No. ICso (ug/mL) SI When the results in Example 17 are evaluated, it is seen that the sample containing at least 95% chlorogenic acid in accordance with the invention has a better anti-inflammatory effect than anti-inflammatory agents such as diclofenac and ibuprofen, which have been used commercially for a long time, even though it is a natural substance. As seen here, better efficacy in terms of COX-1 and COK-2 inhibition compared to the natural agent diclofenac molecule according to the invention, in other words. It shows higher anti-inflammatory effect, specifically COX-1 and COX-2 inhibitory effect. All these experimental data reveal that this standardized substance of natural origin may be an important anti-inflammatory agent. TR TR TR TR

Claims (1)

1.STEMLER Antienflamatuvar ajan olarak kullanim için en az %95 saflikta klorojenik asit. . Istem 1”e göre COX-l, COX-2 ve/veya LOX enzimi inhibitörü olarak kullanim için en az . Istem 1`e göre bir antienflamatuar ajan olup %95 -99 araliginda klorojenik asit içerir. . Istem l”e göre bir antienflamatuar ajan olup 0/0 97-99 araliginda klorojenik asit içerir. . AntienIlamatuvar ajan olarak kullanima uygun, etken madde olarak en az %95 saflikta klorojenik asit içeren farmasötik bilesimler. Istem 5'e göre bir farmasötik bilesim olup ilave olarak bir diger antienflamatuar ajan içerir. . Istem 65ya göre bir farmasötik bilesim olup ilave antienflamatuar ajan diklofenak veya ibuprofendir. . Istem 5-7°den herhangi birine göre bir farmasötik bilesim olup, oral veya topikal kullanima uygun bir dozaj formunda formüle edilmistir. TR TR TR TR1.CLAIM: Chlorogenic acid of at least 95% purity for use as an anti-inflammatory agent. . For use as COX-1, COX-2 and/or LOX enzyme inhibitor according to claim 1, at least . It is an anti-inflammatory agent according to claim 1 and contains 95-99% chlorogenic acid. . It is an anti-inflammatory agent according to claim 1 and contains chlorogenic acid in the range of 0/0 97-99. . Pharmaceutical compositions containing chlorogenic acid of at least 95% purity as the active ingredient, suitable for use as anti-inflammatory agents. A pharmaceutical composition according to claim 5 further comprising another anti-inflammatory agent. . A pharmaceutical composition according to claim 65, wherein the additional anti-inflammatory agent is diclofenac or ibuprofen. . A pharmaceutical composition according to any one of claims 5-7, formulated in a dosage form suitable for oral or topical use. TR TR TR TR
TR2021/021396 2021-12-28 INHIBITORY EFFECTS OF CHLOROGENIC ACID ON COX-1, COX-2 AND LOX ENZYMES TR2021021396A1 (en)

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