TR2021022265A2 - Acetylcholinesterase Inhibitory Activity of Salt Samples of Prulifloxacin Molecule, Prulifloxacin Isomer Molecule Forms, or Their Pharmaceutically Accepted Prulifloxacin Isomer Molecule Forms - Google Patents

Acetylcholinesterase Inhibitory Activity of Salt Samples of Prulifloxacin Molecule, Prulifloxacin Isomer Molecule Forms, or Their Pharmaceutically Accepted Prulifloxacin Isomer Molecule Forms

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TR2021022265A2
TR2021022265A2 TR2021/022265A TR2021022265A TR2021022265A2 TR 2021022265 A2 TR2021022265 A2 TR 2021022265A2 TR 2021/022265 A TR2021/022265 A TR 2021/022265A TR 2021022265 A TR2021022265 A TR 2021022265A TR 2021022265 A2 TR2021022265 A2 TR 2021022265A2
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molecule
prulifloxacin
forms
specified
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TR2021/022265A
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Cenk Sesal Nüzhet
Durdaği Serdar
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Bahcesehir Ueniversitesi
Bahçeşehi̇r Üni̇versi̇tesi̇
T C Marmara Ueniversitesi
Tc Marmara Üni̇versi̇tesi̇
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Publication of TR2021022265A2 publication Critical patent/TR2021022265A2/en

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Abstract

Sunulan buluş, asetilkolinesteraz (AChE) inhibitor özelliği taşıyan prulifloksasin veya prulifloksasin türevlerini veya farmasötik açıdan kabul gören tuzlarının doğal veya sentetik formlarını içeren ve bunların farmasötik bileşim ve fonksiyonel gıda ve taşıyıcılar ile AChE inhibitör molekülü olarak AChE kaynaklı çeşitli hastalıkların ya da bozuklukların tedavisinde kullanılabilir.The present invention can be used in the treatment of various diseases or disorders caused by AChE, containing prulifloxacin or prulifloxacin derivatives with acetylcholinesterase (AChE) inhibitory property, or natural or synthetic forms of their pharmaceutically acceptable salts, as pharmaceutical composition and functional food and carriers, and AChE inhibitor molecule.

Description

TARIFNAME Prulifloksasin Molekülü, Prulifloksasin Izomer Molekül Formlari veya Bunlarin Farmasötik Olarak Kabul Edilen Prulifloksasin Izomer Molekül Formlarinin Tuz Örneklerinin Asetilkolinesteraz Inhibitör Aktivitesi Bulusun Ilgili Oldugu Teknik Saha: Sunulan bulus, prulifloksasin, prulifloksasin derivatiVlerini içeren ve bunlarin farmasötik bilesim ve fonksiyonel gida ve farmasötik açidan kabul gören tuzlarinin asetilkolinesteraz (AChE) Inhibitor özellikleri ile ilgilidir. DESCRIPTION Prulifloxacin Molecule, Prulifloxacin Isomer Molecular Forms or Thereof Salt of Pharmaceutically Acceptable Prulifloxacin Isomer Molecule Forms Acetylcholinesterase Inhibitor Activity of Samples Technical Field to which the Invention Relates: The presented invention contains prulifloxacin, prulifloxacin derivatives and their pharmaceutical preparations. composition and functional food and pharmaceutically acceptable salts of acetylcholinesterase It is related to (AChE) Inhibitor properties.

Teknigin Bilinen Durumu: Bir alkoloid olan asetilkolin tanimlanan ilk nörotransmitterdir. Merkezi sinir sisteminde yer alan bir kimyasal-transmitter (kimyasal-iletici) olmasinin yani sira birçok organizmanin (insanlar dahil) parasempatik sinir siteminde yer almaktadir. Ilk kez 1914 yilinda Ingiliz bilimadami Henry Hallet Dale tarafindan tanimlanan asetilkolin, asetik asitile kolin'in esteridir. 1921 yilinda ise Avustralyali bilim adami Otto Lewi tarafindan, kurbaga kalpleri üzerinde yaptigi deneyler sonucu bir nörotransmitter olarak dogrulanan bu kesif bilimadamlarina 1936'da Nobel Ödülü kazandirmistir. Known Status of the Technique: Acetylcholine, an alkaloid, was the first neurotransmitter identified. Located in the central nervous system In addition to being a chemical-transmitter that receives It is located in the parasympathetic nervous system (including humans). For the first time in 1914, the British Acetylcholine, defined by scientist Henry Hallet Dale, is the compound of choline with acetic acid. is the ester. In 1921, frog hearts were discovered by Australian scientist Otto Lewi. This discovery, which was confirmed as a neurotransmitter as a result of his experiments on It brought scientists the Nobel Prize in 1936.

Asetilkolin belli nöronlarda kolin asetil esteraz enzimi tarafindan, kolin ve asetil-CoA”dan sentez edilir. Sinaptik bosluga salinarak görevini tamamladiktan sonra asetilkolin, asetilkolinesteraz enzimi yardimiyla kolin ve asetik asit tuzu olan asetat'a çevrilerek yikilir. Ayrica, AChE olarak adlandirilan asetilkolinesteraz, hidrolitik aktivitesi Özelligiyle kolin ve asetat grubunu olusturmasiyla, parasempatik nöronlarin aktivitesi araciligiyla nörotransmiter asetilkolinin (ACh) degrede olmasini saglayan bir enzimdir. In certain neurons, acetylcholine is separated from choline and acetyl-CoA by the enzyme acetyl esterase. is synthesized. After completing its task by being released into the synaptic space Acetylcholine is converted into acetate, a salt of choline and acetic acid, with the help of the enzyme acetylcholinesterase. It is turned and destroyed. Additionally, acetylcholinesterase, called AChE, has hydrolytic activity. The activity of parasympathetic neurons, especially by forming the choline and acetate group, increases the activity of parasympathetic neurons. It is an enzyme that enables the degradation of the neurotransmitter acetylcholine (ACh).

AChE, endoplazmik retikulumun zarinda üretildikten sonra islevini gerçeklestirmek için hücre zarina tasinmaktadir. AChE, temel olarak kolinerjik nöronlarda ve çevresinde, özellikle kaslarin baglanti noktalarinda ayrica plazma içinde, karaciger ve diger dokularda bulunan önemli bir enzimdir. To perform its function, AChE is produced in the membrane of the endoplasmic reticulum. is transported to the cell membrane. AChE is mainly produced in and around cholinergic neurons, especially found at the attachment points of the muscles, as well as in the plasma, liver and other tissues It is an important enzyme.

Genellikle asetilkolin, akson ucundaki membrandan sinaptik bosluga dogru salgilanan ve post-sinaptik nöron reseptöiünü baglama yoluyla aksiyon potansiyelini transfer eden nörotransimitterdir. Nörona uyarinin tasinmasindan sonra, AChE ile kolin ve asetata degrede olur, sonra geri emilim yoluyla tekrar yeni asetilkolin molekülleri sentezlemek için kullanilan sinir uçlarina geri tasinir. Generally, acetylcholine is secreted from the membrane at the axon tip towards the synaptic gap and transfers action potential by binding the post-synaptic neuron receptor It is a neurotransmitter. After the stimulus is carried to the neuron, it is degraded to choline and acetate by AChE. occurs, which is then used to synthesize new acetylcholine molecules again through reabsorption. is carried back to the nerve endings.

Asetilkolin arastirmalari, çesitli fiziksel ve mental hastaliklarin/bozukluklarin, asetilkolin mekanizmasinin degregasyonu ve sentezlenen asetil kolin konsantrasyonunun anormal bir düzeyde düsmesi arasinda anlamli bir iliskinin oldugunu ortaya çikartmistir. Acetylcholine research has shown that various physical and mental diseases/disorders, acetylcholine mechanism and an abnormal concentration of synthesized acetylcholine. It has been revealed that there is a significant relationship between the decrease in the level of

Asetilkolinin, bugün Alzheimer ve Parkinson hastaliklarinin patogenezinde (=mekanizmasinda) önemli bir yere sahip oldugu bilinmektedir. Bunaklik olarakta bilenen Alzheimer hastaligi (AD), tipik olarak en fazla bilinen asetilkolin iliskili bozukluktur. Acetylcholine is currently implicated in the pathogenesis of Alzheimer's and Parkinson's diseases. It is known that it has an important place in the mechanism. Also known as dementia Alzheimer's disease (AD) is typically the most well-known acetylcholine-related disorder.

Alzheimer hastaliginin en önemli semptomlari, hafiza kaybi, konusma bozuklugu ve demanstir. Bu güne kadar hastaligin isleyisinde ve patogenezi için çesitli hipotezler ortaya atilsa da yine de tam olarak bilinmemektedir. The most important symptoms of Alzheimer's disease are memory loss, speech impairment and is dementia. To date, various hypotheses have emerged for the mechanism and pathogenesis of the disease. Atilsa is still not fully known.

Bunun yanisira, Alzheimer hastaligina yakalanmis hastalarin merkezi sinir sistemleri genellikle tamir edilemez, ve özellikle de kolinerjik nöronlar tamir edilemez. Bununla birlikte, kolinerjik nöronlarin tamir edilememesiyle Alzheimer hastaligina maruz kalan hastalarin kognitif` basarinin, hafiza ve ögrenmenin azalmasiyla derin bir iliskide oldugu rapor edilmistir. In addition, the central nervous systems of patients with Alzheimer's disease generally cannot be repaired, and cholinergic neurons in particular cannot be repaired. With this, Patients suffering from Alzheimer's disease due to failure of cholinergic neurons to repair Cognitive achievement is reported to be deeply related to decline in memory and learning. has been done.

AD ile iliskili kolinerjik nöronun iyilestirme çabalari kolinerjik hipotez tarafindan öne sürülmektedir. Bu hipoteze göre, AD hastaliginin tedavisinde basarili sonuç elde edebilmesinde, aktif olarak hasar görmüs kolinerjik nöronlarin düzeltilmesi yönünde yapilmasinin gereklliligi belirti lmektedir. Restoration efforts of the cholinergic neuron associated with AD are suggested by the cholinergic hypothesis. is being driven. According to this hypothesis, successful results can be achieved in the treatment of AD disease. towards the restoration of actively damaged cholinergic neurons. The necessity of doing this is stated.

Tamir edilemiyen kolinerjik nöronun iyilestirilmesinde, kolinerjik nörotransmitter olan ACh öncü molekünün kullanilmasi, kolinerjik reseptör agonistlerinin kullanilmasi veya AChE inhibitörleriyle sinaps içinde ACh nin konsantrasyonunu dengede tutacak sekilde bir yöntem uygulanmaktadir. Fakat kolinerjik reseptör agonistleri in ViVO da degrade oldugundan genel olarak AChE inhibitörleri kullanilmaktadir. ACh, a cholinergic neurotransmitter, is used to heal irreparable cholinergic neurons. use of the precursor molecule, use of cholinergic receptor agonists or AChE A method to balance the concentration of ACh in the synapse with its inhibitors is implemented. However, since cholinergic receptor agonists are degraded in ViVO, AChE inhibitors are used.

Asetilkolin eksikligi ile derin bir baglantisi oldugu için asetilkolinesteraz enzimini inhibe eden bazi ilaçlar, Alzheimer hastaligi gibi hastaliklarin tedavisinde kullanilmaktadir. It inhibits the enzyme acetylcholinesterase, as it has a deep connection with acetylcholine deficiency. Some drugs are used to treat diseases such as Alzheimer's disease.

Birnöromaskülerhastalik olan miyasteni gravis'de ise, vücut asetilkolin reseptörlerine karsi antikor üreterek düzgün bir asetilkolin sinyal transferini önledigi bilinmektedir. Bu bozuklugun tedavisinde ise asetilkolinesteraz enzimini inhibe eden Fizostigmin gibi ilaçlar kullanilmaktadir. Ayrica, asetilkolin katarakt aineliyatlari sirasinda göz bebeginin hizli bir sekilde kon striksiyona (küçülme-daralma) ugramasi için kullanilmaktadir. In myasthenia gravis, which is a neuromuscular disease, the body responds to acetylcholine receptors. It is known that it prevents a proper acetylcholine signal transfer by producing antibodies against it. This In the treatment of the disorder, drugs such as Physostigmine, which inhibit the acetylcholinesterase enzyme, are used. is used. Additionally, acetylcholine is a rapid stimulation of the pupil during cataract surgeries. It is used to undergo constriction (shrinkage).

Amerika Gida ve Ilaç Dairesi (FADl, nden onay almis ve Alzheimer için teropatik ilaçlar olarak kullanilan AChE inhibitörleri tacrine (THA, Cognex®), donepezil (Acricept ®) ve rivastigmaine (Exel0n®] ile ömeklendirilebilir. Bunlarin arasinda dogal ürünlen elde edilen bilesikler galanthamine (Galanthus nivalis), huperzine A (Huperzia serrata) ve digerleridir. Therapeutic drugs for Alzheimer's that have been approved by the American Food and Drug Administration (FADl) AChE inhibitors used as tacrine (THA, Cognex®), donepezil (Acricept®) and rivastigmaine (Exel0n®), among which are obtained from natural products compounds are galanthamine (Galanthus nivalis), huperzine A (Huperzia serrata) and others.

ACh degregasyonundan koruma yoluyla ACh°nin konsantrasyonunu sabit tutan AChE inhibitörleri, kognitif (muhakeme, algi) fonksiyon gelistirme etkisine sahiptir. Ancak. AChE inhibitörleri hepatotoksisite, kisa yari ömür, düsük biyo-uyumluluk gibi bilinen birçok probleme sahiptir. Bu nedenle, birçok çalisma yeni AChE inhibitörlerinin gelistirilmesi üzerine yapilmaktadir. AChE keeps the concentration of ACh constant by protecting it from ACh degradation Inhibitors have the effect of improving cognitive (judgment, perception) function. However. AChE Inhibitors have many known properties such as hepatotoxicity, short half-life, low biocompatibility. It has a problem. Therefore, many studies have focused on the development of new AChE inhibitors. It is done on.

Ayni zamanda, kolin sinir sistemi iliskili diger patolojik çalismalarda, gastrointestinal hareketin sinir uyarilari tarafindan kontrol edildigi ve asetilkolinin mide çalismasini arttirdigi rapor edilmistir. Bundan dolayi, AChE inhibitörlerinin bir tipi olan neostigmin, artan postoperatif ileus (ameliyat sonrasi bagirsak tikanmasi) sebebiyle olusan karin sisligi veya Mesane detrüsör yetersizligi sebebiyle olusan disüri (idrar zorlugu) tedavisinde kullanilmaktadir. At the same time, in other pathological studies related to the choline nervous system, gastrointestinal movement is controlled by nerve impulses and acetylcholine increases stomach function has been reported. Therefore, neostigmine, a type of AChE inhibitor, increases abdominal distension due to postoperative ileus (intestinal obstruction after surgery) or In the treatment of dysuria (urinary difficulty) caused by bladder detrusor insufficiency is used.

Ayrica, otoimmün nöromaskuler hastalik olan myasthenia gravis post-sinaptik nöromasküler baglanti noktalarinda asetil kolin reseptörlerinin bozulmasiyla olustugundan nörotransmitter asetil kolinin simulatif (uyarici) etkisi bozulmaktadir. Mestinon veya neostigmine gibi asetil kolin inhibitörleri ile tedavi edilmektedir. Mestinon myasthenia gravis tedavisinde siklikla kullanilmaktadir. Böylece kas hücrelerindeki reseptörler üzerinde asetilkolinin kalmasiyla asetil kolin konsantrasyonu arttirilmaktadir. Kisa sürede tedavi etme avantaj gibi görülse de doza bagli olarak kusma, abdominal agri gibi yan etkiler görülebilmektedir. Myasthenia gravis tedavisinde yeni gelistirilen asetil kolin esteraz inhibitörleri nikotinik veya muskarinik asetil kolin reseptörlerine seçicilik göstermezler, bundan dolayi muskarinik asetil kolin reseptörünün uyarilmasiyla istenmeyen etkiler görülmektedir. Dahasi, emilme oranlari çok düsüktür ve kismen etkili olmalari nedeniyle tedavi araliklari dardir. Additionally, the autoimmune neuromuscular disease myasthenia gravis is associated with post-synaptic neuromuscular disease. neurotransmitter due to the disruption of acetylcholine receptors at their junction points. The simulative (stimulating) effect of acetylcholine is impaired. acetyl such as mestinon or neostigmine It is treated with choline inhibitors. Mestinon is often used in the treatment of myasthenia gravis. is used. Thus, acetylcholine remains on the receptors in the muscle cells. Acetylcholine concentration is increased. Although treatment in a short time seems to be an advantage, Depending on the dose, side effects such as vomiting and abdominal pain may occur. myasthenia Newly developed acetylcholine esterase inhibitors are nicotinic or muscarinic inhibitors in the treatment of gravis. They do not show selectivity for acetylcholine receptors, so muscarinic acetylcholine Undesirable effects occur with stimulation of the receptor. Moreover, their absorption rate is very high. are low and treatment intervals are narrow due to their partial effectiveness.

Glauooma, geri dönüsümsüz görme kaybinin yasandigi, ilerleyen, göz içi basinç nedeniyle optik sinirlerin zarar gördügü bir hastaliktir. Bu baglamda, yer alan bilgiye göre asetilkolin esteraz inhibitörleri sulu sivinin tekrar emilmesini (absorbsiyonunu) saglamaktadir. Böylelikle göz içi basinci düsürülmektedir. Ancak, özellikle dikkat edilmesi gereken konu Glaucoma tedavisinin AChE inhibitörleriyle 6 aydan fazla sürmesi durumunda katarat olusma riski meydana gelmektedir. Glauooma is a progressive, irreversible loss of vision due to intraocular pressure. It is a disease in which the optic nerves are damaged. In this context, according to the information available, acetylcholine Esterase inhibitors ensure the reabsorption of aqueous fluid. Thus intraocular pressure is reduced. However, the issue that needs particular attention is Glaucoma. Risk of catarrh formation if treatment with AChE inhibitors continues for more than 6 months is occurring.

ACh konsantrasyonu azligi ile iliskili olarak çesitli hastalik ya da bozukluklarin tedavi ya da korunmasinda, ACh sentezini kolaylastirmak için öncü ACh moleküllerinin tatbik edilmesi bir kez alternatif metot olarak önerilmektedir. Buna karsin, kan beyin bariyerine girmeden kisa-zamanli etkilesimlerinden dolayi Tacrin gibi ACh hidrolitik aktivitesine sahip AChE ilaçlar tedavide çogunlukla kullanilmaktadir. Treatment or treatment of various diseases or disorders associated with low ACh concentration application of precursor ACh molecules to facilitate ACh synthesis in It is recommended as an alternative method. However, without entering the blood brain barrier AChE with ACh hydrolytic activity, such as Tacrin, due to their short-time interactions Medicines are mostly used in treatment.

Yukarida da bahsedildigi gibi günümüzde gelistirilen ve ticari olarak satilan AChE inhibitörlerinin hepatopati, gastrointestinal dagilim (abdominal agri veya kusma), kas agrisi ve benzerleri gibi birçok yan etkileri bulunmaktadir. As mentioned above, currently developed and commercially available AChE Hepatopathy, gastrointestinal distribution (abdominal pain or vomiting), muscle pain It has many side effects such as etc.

PruIiroksasin, floroquinolon (fluoroquinolonei ilaç sinifinin en eski sentetik anibiyotigidir. Pruiroxacin is the oldest synthetic antibiotic of the fluoroquinolone drug class.

Pmlifloksasin öncü bir ilaçtir. Italya7da solunum ve israr yolu enfeksiyonlarinda, Japonyaida diyare enfeksiyonlarinda komplikasyonsuz olarak tedavi ettigi onaylanmistir. Pmlifloxacin is a pioneer drug. In respiratory and urinary tract infections in Italy, in Japan It has been approved to treat diarrheal infections without complications.

Yapilan iri sliko hesaplamalar sonucunda prulifloksasinin çesitli formlarinin asetil kolin esteraz enziminin aktivitesini azalttigi hatta bu etkinin günümüzde AChE inhibitörü olarak kullanilan ilaçlardan çok daha güçlü bir etkiye sahip oldugu gözlenmistir. As a result of large-scale calculations, various forms of prulifloxacin have higher levels of acetylcholine. It reduces the activity of the esterase enzyme and even has this effect today as an AChE inhibitor. It has been observed that it has a much stronger effect than the drugs used.

Bu nedenle sunulan bulus, aSetilkolin konsantrasyonundaki anormal düsüs ile ilgili çesitli hastalik ve rahatsizliklarin tedavisinde kullanilabilecek bir molekül önermektedir. Bu molekül yüksek oranda asetikkolin estreaz inhibisyonu aktivitesine sahip sentetik olarak elde edilebilen çesitli formlardaki prulifloksasin molekülü ile ilgilidir. Therefore, the presented invention covers various problems related to the abnormal decrease in aCetylcholine concentration. It proposes a molecule that can be used in the treatment of diseases and disorders. this molecule It is synthetically obtained with high aceticcholine estrease inhibition activity. It relates to the prulifloxacin molecule in various forms that can be obtained.

Bulusun Çözümünü Amaçladigi Teknik Problemler: Sunulan bulusun amaci, AChE inhibisyonu aktivitesine sahip olarak prulifloksasin molekülünün belirlenmesidir. Technical Problems That the Invention Aims to Solve: The aim of the present invention is to provide prulifloxacin with AChE inhibition activity. determination of the molecule.

Sunulan bulusun diger amaci, AChE inhibisyonu aktivitesine sahip olarak çesitli prulifloksasin izomer molekül formlarinin belirlenmesidir. Another aim of the present invention is to use various compounds with AChE inhibition activity. Determination of prulifloxacin isomer molecular forms.

Sunulan bulusun diger bir amaci, prulifloksasin molekülünün veya çesitli prulifloksasin izomer molekül formlarinin veya AChE aktivitesini inhibe edebilme yetenegine sahip olan farmasötik olarak kabul edilen tuzlarinin bei Irlenmesidir. Another object of the present invention is to use the prulifloxacin molecule or various prulifloxacin isomeric forms of molecules or have the ability to inhibit AChE activity It is the preparation of pharmaceutically acceptable salts.

Sunulan bulusun diger bir amaci, gastrointestinal bölgenin düz kaslarinin zayifliginda (miyasteni), mesanede, nörodejeneratif hastaliklarin veya glaucomainin tedavisinde veya korumasinda farmasötik kompozisyon saglanmasi veya farmasötik olarak kabul edilen prulifloksasin molekülünün veya çesitli prulifloksasin izomer molekül formlarinin tuzlarinin belirlenmesidir. Another purpose of the presented invention is to treat the weakness of the smooth muscles of the gastrointestinal region. (myasthenia), bladder, in the treatment of neurodegenerative diseases or glaucoma or providing pharmaceutical composition or pharmaceutically acceptable Salts of the prulifloxacin molecule or various prulifloxacin isomer molecule forms is to be determined.

Sunulan bulusun bir baska amaci, gastrointestinal bölgenin düz kaslarinin zayifliginda (miyasteni), mesanede, nörodejeneratif hastaliklarin veya glaucomainin tedavisinde veya korumasinda farmasötik kompozisyon saglanmasi veya farmasötik olarak kabul edilen prulifloksasin molekülünün veya çesitli prulifloksasin izomer molekül formlarinin tuzlarinin kullanilmasidir. Another purpose of the presented invention is to treat the weakness of the smooth muscles of the gastrointestinal region. (myasthenia), bladder, in the treatment of neurodegenerative diseases or glaucoma or providing pharmaceutical composition or pharmaceutically acceptable Salts of the prulifloxacin molecule or various prulifloxacin isomer molecule forms is to use.

Sunulan bulusun diger bir amaci, gastrointestinal bölgenin düz kaslarinin zayifligi (miyasteni)nda, mesanede, nörodejeneratif hastaliklarin veya glaucoma'nin tedavisinde veya korumasinda farmasötik kompozisyon saglanmasi veya farrnasötik olarak kabul edilen prulifloksasin molekülünün veya çesitli prulifloksasin izomer molekül formlarinin tuzlarinin kullanilmasidir. Another purpose of the presented invention is to treat the weakness of the smooth muscles of the gastrointestinal region. (myasthenia), bladder, in the treatment of neurodegenerative diseases or glaucoma or providing pharmaceutical composition or pharmaceutically acceptable Salts of the prulifloxacin molecule or various prulifloxacin isomer molecule forms is to use.

Pruiifloksasin molekülü veya çesitli prulifloksasin izomer molekül formlari veya farmasötik olarak kabul edilen tuzlari, AChE aktivitesini inhibe eden potansiyel asetil kolin esteraz inhibitörüdür. Böylelikle, farrnasötik kompozisyon ya da tasiyici içinde yer almasiyla gastrointestinal bölgenin düz kaslarinin zayifliginda (miyasteni), mesanede, nörodejeneratif hastaliklarin veya glaucoma7nin tedavisinde veya korumasinda farmasötik kompozisyon saglanmasi veya farmasötik olarak kabul edilen prulifloksasin molekülünün veya çesitli prulifloksasin izomer molekül formlarinin tuzlarinin kullanilmasidir. Pruiifloxacin molecule or various prulifloxacin isomer molecule forms or pharmaceutical Salts considered to be potent acetylcholine esterase inhibitors inhibit AChE activity. It is an inhibitor. Thus, by being included in the pharmaceutical composition or carrier, weakness of the smooth muscles of the gastrointestinal tract (myasthenia), bladder, neurodegenerative Pharmaceutical composition for the treatment or prevention of diseases or glaucoma providing or using the pharmaceutically acceptable prulifloxacin molecule or various It is the use of salts of prulifloxacin isomer molecular forms.

Bulusun Açiklamasi: Aksi tanimlanana kadar burada belirtilen teknik ve bilimsel terimler, yaygin olarak bulusun ait Oldugu teknik alanda siradan tecrübeli bir kisi tarafindan genel olarak anlasilanla ayni anlama sahiptir. Description of the invention: Unless otherwise defined, technical and scientific terms used herein are commonly used to describe the invention. The same understanding as is generally understood by a person of ordinary skill in the technical field in which it is applied. has.

Sunulan bulusta, prulifloksasin molekülünün veya çesitli prulifloksasin izomer molekül formlarinin veya çesitli prulifloksasin izomer molekül formlarinin tuzlarinin AChE inhibisyonunu saglayan aktivitesi bulundugu belirtilmektedir. In the present invention, the prulifloxacin molecule or various prulifloxacin isomer molecules AChE forms or salts of various prulifloxacin isomer molecular forms It is stated that it has inhibitory activity.

Sunulan bulus, AChE olarakta bilinen “asetil kolin esterazin sahip oldugu hidrolitik aktivite yardimiyla nörotransmitter asetil kolini degrede eden, kolin ve asetat grubu olusturan ve asetil kolin konsantrasyonunda derin degisikliklere sebep olabilen bir enzim ile ilgilidir. Iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol bagimliligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) gibi anormal asetil kolin konsantrasyonunun azalmasi ile iliskili çesitli hastaliklarin veya bozukluklarin tedavisinde kullanilabilecektir. The presented invention is based on the hydrolytic activity of acetylcholine esterase, also known as AChE. It degrades the neurotransmitter acetylcholine, forming choline and acetate groups with the help of acetyl It is related to an enzyme that can cause profound changes in choline concentration. ischemic Neurodegenerative diseases such as brain disease, myasthenia gravis, memory defects, alcohol addiction diseases, myasthenas (weakening) of gastrointestinal smooth muscle or glaucoma or urinary tract various diseases associated with abnormal decrease in acetylcholine concentration, such as in the bladder It can be used to treat diseases or disorders.

Bazi prulifloksasin izomer molekül formlari veya bunlarin farmasötik olarak kabul edilen prulifloksasin izomer molekül formlarinin tuzlari daha yüksek potansiyel AChE inhibitör aktivitesi gösterme özelligine sahip olabilirler. Some prulifloxacin isomeric molecular forms or their pharmaceutically acceptable Salts of prulifloxacin isomer molecular forms have higher potential AChE inhibitors. They may have the feature of showing activity.

Sunulan bulusta, prulifloksasin molekülünün veya çesitli prulifloksasin izomer molekül formlarinin veya çesitli prulifloksasin izomer molekül formlarinin tuzlari Iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol bagimliligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) gibi anormal asetil kolin konsantrasyonunun azalmasi ile iliskili çesitli hastaliklarin veya bozukluklarin tedavisinde kullanilabilecektir. In the present invention, the prulifloxacin molecule or various prulifloxacin isomer molecules Ischemic brain neurodegenerative diseases such as disease, myasthenia gravis, memory defects, alcohol addiction diseases, myasthenas (weakening) of gastrointestinal smooth muscle or glaucoma or urinary tract various diseases associated with abnormal decrease in acetylcholine concentration, such as in the bladder It can be used to treat diseases or disorders.

Sekil 1”de yer alan prulifloksasin izomer molekül formlari bir antibiyotiktir. Sunulan bulusta, prulifloksasin inolekülünün farmasötik olarak kabul edilebilecek tuzlarini da kapsamaktadir. Prulifloxacin isomer molecule forms shown in Figure 1 are an antibiotic. In the presented invention, It also includes pharmaceutically acceptable salts of the prulifloxacin inoleculum.

Aksi tanimlanmadikça, prulifloksasinin farmasötik tuzlari veya prulifloksasin üzerinde bazik gruplarin veya asidik tuzlari içerebilir. Asidik veya bazik gruplara örnek olarak gösterilebilecek hidroksil gruplari, sodyum, potasyum, kalsiyum, potasyum tuzlari ve hidrobrornid tuzlari, amidojen gruplari, amino gruplarinin p-toluene sulfonat (Tosylate) ve metan sulfonat (mesylate) madelat, laktat, tartarat, sitrat. suksinat, asetat, dihidroejen fosfat, hidrojen fosfat, fosfat, hidrosülfat gruplari ile arka planda yer alan metotlar veya islemler kullanilarak hazirlanabilir. Pharmaceutical salts of prulifloxacin or alkaline salts of prulifloxacin unless otherwise specified. may contain groups or acidic salts. Examples of acidic or basic groups hydroxyl groups, sodium, potassium, calcium, potassium salts and hydrobronide salts, amidogen groups, amino groups p-toluene sulfonate (Tosylate) and methane sulfonate (mesylate) madelate, lactate, tartrate, citrate. succinate, acetate, dihydrogen phosphate, background methods or processes with hydrogen phosphate, phosphate, hydrosulfate groups It can be prepared using .

Buna ek olarak, serbest asit ile asit eklenmis tuz sunulan bulusun farmasötik olarak kabul edilebilen tuzlari için kullanilabilir. Asit eklenmis tuz, fazla miktarda asit solüsyonuyla çözülen bilesikler, bunu metanol, etanol, aseton, veya asetonitril gibi suda çözünebilen organik çözüeüler ile asit eklenmis tuzlarin çöktürülmesi takip eder. Bilesiklerin benzer molar miktarlari ve glisol monoetil eter gibi alkol veya su içindeki asitler isitilabilir ve sonra elde edilen karisim buharlastirilarak veya kurutulur veya çöktürülen tuz emme ile filtre edilebilir. In addition, the free acid and the acid added salt are pharmaceutically acceptable. It can be used for its soluble salts. Acid-added salt, with a large amount of acid solution soluble compounds, followed by water-soluble compounds such as methanol, ethanol, acetone, or acetonitrile. followed by the precipitation of organic solutions and acidic salts. Compounds with similar molar amounts and acids in alcohol or water, such as glycol monoethyl ether, can be heated and then obtained The resulting mixture can be evaporated or dried, or the precipitated salt can be filtered by suction.

Organik asit veya inorganik asit serbest asit olarak kullanilabilir. Organik asit örnekleri hidroklorik asit, fosforik asit, nitrik asit veya tartarik asit, inorganik asit örnekleri metan sulfonik asit, p-toluen, sulfonik asit, asetik asit, trifloroasetik asit, sitrik asit, maleik asit, suksinik asit, oksalik asit, benzoik asit, fumarik asit, mandelik asit, propionik asit, laktik asit, glisolik asiti glukonik asit, galakturonik asit, glutamik asit, glutarik asit, glukuronik asit, aspartik asit, askorpik asit, karbonik asit, vanilik asit, hidroiyodik asit ve benzerleridir. Organic acid or inorganic acid can be used as free acid. Examples of organic acids hydrochloric acid, phosphoric acid, nitric acid or tartaric acid, examples of inorganic acids are methane sulfonic acid, p-toluene, sulfonic acid, acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, fumaric acid, mandelic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorpic acid, carbonic acid, vanillic acid, hydroiodic acid and the like.

Baz ile farrnasötik metal tuzlarinin olusmasi, sunulan bulus için kullanilabilir. Alkali veya toprak alkali metal tuzlari, alkalin metal hidroksidin içinde bilesigin veya toprak alkali metal tuzlarinda çözünmesi, bilesiklerin çözülmeyen tuzlarindan filtre edilmesi ve buharlastirilmasi ve filtre edilerek kurutulmasi ile geleneksel metotlar ile elde edilebilir. The formation of pharmaceutical metal salts with base can be used for the present invention. alkaline or alkaline earth metal salts, compound in alkaline metal hydroxide or alkaline earth metal dissolving in salts, filtering and evaporating compounds from insoluble salts It can be obtained by traditional methods by filtering and drying.

Sodyum potasyum kalsiyum tuzlari tercih edilebilir ve sodyum potasyum ile reaksiyonu ile hazirlanan gümüs tuzlar] veya uygun gümüs tuzlari (ör. gümüs nitrat) ile kalsiyum tuzlar] yine tercih edilebilir. Sodium potassium calcium salts may be preferred and are formed by the reaction of sodium with potassium. prepared silver salts] or calcium salts with suitable silver salts (e.g. silver nitrate)] preferable.

Sunulan bulus, AChE aktivitesi tarafindan ACh konsantrasyonu içindeki azalina ile iliskili iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol aliskanligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) gibi abnormal asetil kolin konsantrasyonunun azalmasi ile ilgili hastaliklarin/bozukluklann tedavisinde veya hastaliklara karsi korumasinda farmasötik bilesik saglar. The present invention relates to the decrease in ACh concentration by AChE activity. such as ischemic brain disease, myasthenia gravis, memory defects, alcohol habit neurodegenerative diseases, myasthenia (weakening) of gastrointestinal smooth muscle, or Abnormally decreased acetylcholine concentration, such as glaucoma or urinary tract (bladder) in the treatment of or protection against diseases/disorders related to Provides pharmaceutical compound.

Sunulan bulusun fannasötik kompozisyonu, farmasötik olarak kabul edilen tasiyicilar ve/veya hazirlanacak olan ilaçlara uygun bir sekil veya güzel bir tat vermesi için katilan madde (eksipiyan) ile birlikte formulasyonlar olusturabilir. Uygun tasiyici ve eksipiyan örnekleri laktoz, dekstroz, sorbitol, mannitol, xylitol, maltitol, nisasta, acacia, alginat, jelatin, kalsiyum fosfat, kalsiyum silikat, selüloz, metil selüloz, mikrokristalin selüloz, polyvinilpirolidon, su, metilhidroksi benzonat, propilhidroksibenzolat, talk, magnezyum seterat ve mineral yagdir. The pharmaceutical composition of the present invention may be based on pharmaceutically acceptable carriers and/or substance added to medicines to be prepared to give them a suitable shape or a pleasant taste It can form formulations with (excipient). Examples of suitable carriers and excipients lactose, dextrose, sorbitol, mannitol, xylitol, maltitol, starch, acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxy benzonate, propylhydroxybenzolate, talc, magnesium cetarate and mineral oil.

Istisnai sekilde bulus bilesigi antikoagulant, koruyucu olabilir. Exceptionally, the compound of the invention may be anticoagulant and protective.

Sunulan bulusun farmasötik kompozisyonu, agiz, nebülize, topical (bukkal, sublingual, dermal ve intraokuler yolun içinde bulundugu), parenteral (subkutan, intradermal, intra periodontal, intracerobrospiral, intrakas, intravasküler ve intraartikular yolla) veya transdermal yolla uygulanmasina ragmen sadece bu yollarla sinirli kalmaz. The pharmaceutical composition of the presented invention can be used in oral, nebulized, topical (buccal, sublingual, including the dermal and intraocular route), parenteral (subcutaneous, intradermal, intraocular) periodontal, intracerobrospiral, intramuscular, intravascular and intraarticular routes) or Although it is applied transdermally, it is not limited to these methods only.

Bununla birlikte, sunulan bulus kompozisyonunun, tek basina ya da AChE inhibitörü geçmisi olan diger ilaçlar ile birlikte kullanilabilmesidir. Asetilkolin esteraz inhibitor örnekleri, Aricept (donepezil hydrochloride capsule commercialized by Eisai), Amirine (Nikken), SM- Zifrosilone (Marion Merrel Dow)dir. Bu asetil kolin inhibitörleri Brufani et al.(Alzheimer Schmidt et al. (Alzheimer Disease: From Molecular Biology to Therapy, eds. Becker et al., tarafindan patentlenmistir. However, the composition of the present invention cannot be used alone or with an AChE inhibitor background. It can be used together with other drugs. Examples of acetylcholine esterase inhibitors, Aricept (donepezil hydrochloride capsule commercialized by Eisai), Amirine (Nikken), SM- Zifrosilone (Marion Merrel Dow). These acetylcholine inhibitors Brufani et al. (Alzheimer's Schmidt et al. (Alzheimer Disease: From Molecular Biology to Therapy, eds. Becker et al., Patented by.

Sunulan bulus kompozisyonu Iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol bagimliligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) gibi hastaliklarin erken evrelerinde hatta hastaliklarin ilerleyen evrelerinde de kullanilabilir. verilebilir fakat bunun limiti yoktur. Yine, Iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol bagimliligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) gibi hastaliklarindan korunmada kullanilabilmesidir. Sunulan bulus kompozisyonunun gerektigi kadar tekrar ile uygulanabilmesidir. Örnegin, klinik olarak hastanin ihtiyacina göre günlük veya 1-12 hafta araliginda, tercihen 3-8 hafta fakat bu limitlere bagli olmayarak uygun araliklarda veya hastanin günlük klinik ihtiyacina göre uygulanabilir. The presented invention composition is used for ischemic brain disease, myasthenia gravis, memory defects, neurodegenerative diseases such as alcohol dependence, myasthenas of gastrointestinal smooth muscle (weakening) or in the early stages of diseases such as glaucoma or urinary cavity (bladder) It can even be used in the later stages of the disease. can be given, but there is no limit. Again, Ischemic brain disease, myasthenia gravis, memory defects, neurodegenerative diseases such as alcohol dependence, gastrointestinal smooth muscle diseases such as myasthenas (weakening) or glaucoma or urinary tract (bladder) can be used for protection. The presented invention composition can be repeated as many times as necessary. is applicability. For example, daily or 1-12 weeks depending on the clinical need of the patient. in the range, preferably 3-8 weeks, but not depending on these limits, at appropriate intervals or It can be applied according to the daily clinical needs of the patient.

Sunulan bulusun kompozisyonu aktif malzemelerin salinmasi veya hizlica saglanmasi formule edilebilir. Bu formulasyonlar tablet, toz, süspansiyon, emülsiyon, solusyon, surup, aerosol, steril enjekte edilebilen solüsyon, sert kapsül, sterile toz ve benzeri sekilde olabilmesidir. Sunulan projenin kompozisyonu tek doz formunda saglanmasinin tercih edilmesidir. The composition of the presented invention provides the release or rapid release of active ingredients. can be formulated. These formulations are tablet, powder, suspension, emulsion, solution, syrup, aerosol, sterile injectable solution, hard capsule, sterile powder and so on is possible. It is preferable to provide the composition of the presented project in single dose form. is to be done.

Sunulan bulus kompozisyonu, teröpotik olarak etkili miktarda uygulanabilir. Terpotik olarak etkili miktar hastaligi ve bozuklugu tedavi edebilecek doz olarak ifade edilebilir. The composition of the present invention can be administered in a therapeutically effective amount. therapeutically The effective amount can be expressed as the dose that can treat the disease or disorder.

Sunulan bulus kompozisyonu, teröpatik olarak etkili miktari hasta semptomlarinin çesitligi, tedavinin periyodu, eksresyon hizi, verilme yolu, verilme zamani, gida, bireysel hastanin cinsi, reaksiyon hasssasiyeti, sagligi, kilosu, yasi tedavi sartlarinin da içinde bulundugu çesitli faktörlerin isiginda tanimlanmistir. Yukarida verilen dozlar yapilan tüm tedavileri kapsamamaktadir. Örnegin, insan haricindeki hayvanlar için bulus kompozisyonunun tek en tercih edilen 500-1000 IU/kg dir. Daha ileri, insan için bulus kompozisyonunun tek dozu vücut agirligindan bagimsiz olarak uygulanabilir. The composition of the present invention, its therapeutically effective amount, variety of patient symptoms, period of treatment, rate of excretion, route of administration, time of administration, food, individual patient Various factors, including breed, reaction sensitivity, health, weight, age and treatment conditions. defined in the light of factors. The doses given above will cover all treatments. It does not cover. For example, for animals other than humans, the composition of the invention is unique The most preferred is 500-1000 IU/kg. Further, a single dose of the composition of the invention for humans It can be applied regardless of body weight.

Diger bir yandan, sunulan bulus koruma için kullanilacak metotlarla veya iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol bagimliligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) gibi anormal asetil kolin konsantrasyonunun azalmasi ile iliskili çesitli hastaliklarin veya bozukluklarin tedavisinde prulifloksasin molekülü veya prulifloksasin izomer molekül formlari veya bunlarin farmasötik olarak kabul edilen prulifloksasin izomer molekül formlarinin tuzlari kullanilabilir. On the other hand, the presented invention relates to methods to be used for protection or ischemic brain neurodegenerative diseases such as disease, myasthenia gravis, memory defects, alcohol addiction diseases, myasthenas (weakening) of gastrointestinal smooth muscle or glaucoma or urinary tract various diseases associated with abnormal decrease in acetylcholine concentration, such as in the bladder prulifloxacin molecule or prulifloxacin in the treatment of diseases or disorders isomer molecule forms or the pharmaceutically acceptable prulifloxacin isomer thereof Salts of the molecular forms can be used.

Burada kullanilan koruma ve tedavi terimleri koruma veya koruma metotlarini ve töropatik ölçümleri refere eder. Böylelikle, sunulan bulus ortamdaki tedaviye ihtiyaç duyan örnegi Iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol bagimliligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) gibi hastaliklardan korunmada kullanilabilir. Burada örnek olarak tanimlanan canlinin anlami insan, primatlar ve tedaviye ihtiyaç duyan kedi, köpek, domuz, at köpek VS. gibi memelileri kapsamaktadir. The terms prevention and treatment used herein refer to prevention or protection methods and therapeutic methods. refers to measurements. Thus, the presented invention can treat the sample in need of treatment in the environment. Such as ischemic brain disease, myasthenia gravis, memory defects, alcohol addiction neurodegenerative diseases, myasthenia (weakening) of gastrointestinal smooth muscle, or It can be used to protect against diseases such as glaucoma or urinary tract (bladder). Here The living thing defined as an example means humans, primates and cats in need of treatment. dog, pig, horse dog etc. It includes mammals such as.

Diger somut örnek, sunulan bulusun komma için kullanilabilecegi saglikli gida veya hastaliklar/bozukluklar asetil kolin esteraz aktivitesi tarafindan asetil kolin konsantrasyonu içindeki azalma ile iliskili iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol bagimliligi gibi nörodejeneratif hastaliklar, gastrointestinal düz kasin zayiflamasi (myasthena) veya glaucoma veya uriner bosluk (mesane) gibi abnormal asetil kolin konsantrasyonunun azalmasi ile ilgili hasta]iklarin/bozukluklarin tedavisinde veya hastaliklara karsi korumasinda kullanilabilecek farmasötik bilesik ile iliskilidir. Another embodiment is the use of healthy food or food products in which the presented invention can be used for coma. diseases/disorders acetylcholine concentration by acetylcholine esterase activity ischemic brain disease, myasthenia gravis, memory defects, alcoholism associated with a decrease in Neurodegenerative diseases such as addiction, weakening of gastrointestinal smooth muscle (myasthena) or abnormal acetylcholine concentration, such as glaucoma or urinary tract (bladder) in the treatment of diseases/disorders related to the decrease in It is related to the pharmaceutical compound that may be used.

Sunulan bulusun saglikli gidasi prulifloksasin molekülü veya prulifloksasin izomer molekül formlari veya bunlarin farmasötik olarak kabul edilen prulifloksasin izomer molekül formlarinin tuzlari yalniz basina veya diger besinlerle birlikte içerebilir. Daha çok, saglikli besin için bulus geleneksel metotlara göre kullanilabilir. Gida içindeki içeriklerin orani kullanim amacina (koruma, saglik veya hastaliklarin tedavisi) bagli olarak belirlenebilir. The healthy food of the presented invention is prulifloxacin molecule or prulifloxacin isomer molecule forms or pharmaceutically acceptable prulifloxacin isomer molecules thereof Salts of these forms can be contained alone or with other foods. More, healthy The invention for food can be used according to traditional methods. Ratio of ingredients in food It can be determined depending on the intended use (protection, health or treatment of diseases).

Genel olarak, prulifloksasin molekülü veya prulifloksasin izomer molekül formlari veya bunlarin farmasötik olarak kabul edilen prulifloksasin izomer molekül formlarinin tuz örnekleri agirligin %10 u kadar veya daha az, tercihen %5 veya daha az besin veya içecek hazirlamasi için eklenebilir. Ancak, sagligin korunmasi için uzun süreli besin alimlarinda aktif malzemenin daha düsük miktarini da içerebilir. Bunun yaninda, sunulan bulus herhangi bir zararli etki olusturmadigi durumda, bilinen miktardan daha fazla aktif malzeme kullanilabilir. In general, prulifloxacin molecule or prulifloxacin isomer molecule forms or salts of their pharmaceutically acceptable prulifloxacin isomer molecular forms. samples 10% or less, preferably 5% or less, by weight of food or drink can be added for preparation. However, in order to protect health, long-term food intake It may also contain lower amounts of the active ingredient. Besides, the presented invention is not greater than the known amount of active ingredient, unless it produces a harmful effect. can be used.

Saglikli gida çesidinde sinir yoktur. Saglikli gidanin örneklerinin karistirilabilecegi prulifloksasin molekülü veya prulifloksasin izomer molekül formlari veya bunlarin farmasötik olarak kabul edilen prulifloksasin izomer molekül formlarinin tuz örnekleri, gidalar, sosis, ekmek, çikolata, sekerler, sekerlemeler, pizza, sakizlar, dondurma Vb. gibi günlük ürünler, çesitli çorbalarda, içeceklerde, çay, alkolik içecekler ve vitamin kompozisyonunda kullanilabilir. Sunulan bulusun besinleri geleneksel/ticari olarak satilan saglikli besinlerin Eger Sunulan bulusun besini saglikli içeceklerse, saglikli içecekler çesitli tatlandirici ajanlar, dogal hidrokarbonlar veya eklenen komponentin ticari içeceklerine benzer sekilde içerebilir. There is no limit to the variety of healthy foods. Where samples of healthy food can be mixed prulifloxacin molecule or prulifloxacin isomer molecule forms or their pharmaceutical forms Salt samples of prulifloxacin isomer molecular forms, foods, sausages, bread, chocolate, candies, candies, pizza, gummies, ice cream Etc. daily products such as, in various soups, beverages, tea, alcoholic beverages and vitamin composition can be used. The nutrients of the presented invention are those of traditional/commercially sold healthy foods. If the food of the presented invention is healthy drinks, healthy drinks contain various sweetening agents, It may contain natural hydrocarbons or an added component similar to commercial beverages.

Dogal hidrokarbonlar glikoz veya fruktoz gibi monosakkaritler, maltoz ve sukroz gibi disakkaritlerde, siklodekstrin veya dekstrin gibi dogal tatlandiricilar veya sakkarin veya aspartam gibi sentetik tatlandiricilar olabilir. Dogal hidrokarbonlarin orani saglikli içeceklerin Bunlara ek olarak, sunulan bulusun besini çesitli gida katki maddelerini, Vitamin, elektroli, boyayici ajanlar, koruyucu ajanlar, pektik asit ve tuzlari, alginik asit ve tuzlari, organik asit, koruyucu Viskoz ajanlar, pH kontrol edici ajanlar, sabitlestiriciler, gliserin, alkol ve karbonizasyon ajanlari karbonatlanmis ürünler için kullanilabilir. Bununla beraber, sunulan bulusun besini dogal meyve suyu, meyve suyu içecekleri ve sebze suyu içecekleri için taze meyve ve sebze seçilebilir. Belirtilen katkilarin oranlari çok kritik degil genellikle bulus besinin agirliginin yüzde biri kadar seçilebilir. Natural hydrocarbons include monosaccharides such as glucose or fructose, maltose and sucrose. in disaccharides, natural sweeteners such as cyclodextrin or dextrin or saccharin or There may be synthetic sweeteners such as aspartame. The ratio of natural hydrocarbons in healthy drinks In addition, the food of the presented invention contains various food additives, vitamins, electrolytes, dyeing agents, protective agents, pectic acid and its salts, alginic acid and its salts, organic acid, preservatives Viscous agents, pH controlling agents, stabilizers, glycerin, alcohol and Carbonizing agents can be used for carbonated products. However, offered The food of the invention is fresh for natural fruit juice, fruit juice drinks and vegetable juice drinks. Fruits and vegetables can be chosen. The proportions of the specified additives are not very critical and are generally It can be selected as one percent of the weight of the food.

Claims (1)

ISTEMLER . Etkili miktarda molekülün hücreler ile temas ettirilmesine dayanan uygulama Olup, özelligi; molekül veya izomer molekül formlari veya farinasötik olarak kabul edilen tuzlarinin, dogal ya da sentetik formlari ile asetil kolin esteraz (AChE) inhibitör (AChEI) aktivitesine sahip olmasidir. . Iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol aliskanligi gibi nörodejeneratif hastaliklar, Alzeimer hastaligi, Parkinson hastaligi, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) hastaliklarin ortak nedeni AChE ile ilgili olup, özelligi; Istem lide adi geçen molekül ve molekül formlarinin hastaliklarin tedavisinde kullanilabilecek AChEI aktiviteye sahip olmasidir. . Isteml`de molekül olarak belirtilen madde sunulan bulus prulifloksasin molekülü olup, özelligi; AChEI aktivitesine sahip olmasidir. . Isteml 'de sunulan bulus prulifloksasin molekülünün dogal ya da sentetik fonnu veya molekülünün farmasötik olarak kabul edilen tuzlari Olup, özelligi; prulifloksasin molekülünün dogal veya sentetik formu veya molekülün farmasötik olarak kabul edilen tuzlarinin AChEI aktivitesine sahip olmasidir. . lsteml*de sunulan prulifloksasin molekülü ve molekülün farmasötik tuzlari olup, özelligi; bazik gruplari veya asidik tuzlari içermesiyle hidroksil gruplari, sodyum, potasyum, kalsiyum, potasyum tuzlari ve hidrobromid tuzlari, amino gruplarinin p- toluene sulfonat (Tosylate), metan sulfonat (mesylate) madelat, laktat, tartarat, sitrat, suksinat, asetat, dihidroejen fosfat, hidrojen fosfat, fosfat, hidrosülfat gruplarina sahip olmasidir. . Istem 1, 4 veya 5”teki prulifloksasin molekülü veya formlarinin canlilar üzerinde hastalik tedavisinde kullanilabilmesi olup, özelligi; Iskemik beyin hastaligi, myasthenia gravis, hafiza defektleri, alkol aliskanligi gibi nörodejeneratif hastaliklar, Alzeimer hastaligi, Parkinson hastaligi, gastrointestinal düz kasin myasthenasi (zayiflamasi) veya glaucoma veya uriner bosluk (mesane) hastaliklarin tedavilerinde, hastalik etkilerinin azaltilmasinda veya hastalik sonucu olusan bozukluklari tedavi etmede kullanilabilecek etkili miktarda (dozda) prulifloksasin molekül ya da farmasötik olarak kabul edilen tuzlarinin AChEI aktivitesine sahip olmasidir. . Canlilarda lstem2°de belirtilen hastaliklarin nedeni AChE ile iliskili olup, özelligi; Istem 3, 4 veya 5”teki gibi prulifloksasin molekülü ve formlarinin bir teknik yardimiyla Isteml”de belirtildigi sekilde etkili miktarda temas edilmesiyle terapötik etkiye sahip olmasidir. Istem7'de canlilar olarak belirtilen memeliler; insan, köpek, kedi, inek, öküz, manda, koyun, kuzu, koç, keçi, kanatlilar; tavuk, muhabbet kusu, güvercin, papagan ve hindiler ile Istem2°de belirtilen hastaliklarin tedavi edici moleküller ile temasi olup, özelligi; Istem3“de sunulan bulus prulifloksasin molekülü veya Istem4 veya 5“te belirtilen formlarinin canlilar üzerinde AChEI etkisi nedeniyle Istedee belirtildigi sekliyle terapötik etkiye sahip olmasidir. Istem 2°de belirtilen hastaliklarin tedavisi, tedavi edici moleküller ile hücrelerin iri vivo temas ettirilmesi olup, özelligi; Istem 3, 4 veya 5,teki gibi prulifloksasin inolekülü ve formlarinin terapötik etken olarak kullanilabilme yetenegine sahip olmasidir. .Istem3`de sunulan bulus prulifloksasin molekülü veya Istem4 veya 5”te belirtilen formlari, Istem 2”de belirtilen hastaliklari, Istem 9'da belirtildigi sekilde terapötik etkenler olup, özelligi; AChEI terapötik olarak kullaniminda ayni formülasyon içinde tatbik edilebilme yetenegine sahip olmasidir. Istem 3tte sunulan prulifloksasin molekülü veya Istem4 veya 5'te belirtilen formlari Istem2`de belirtilen hastaliklari Istem9'da belirtildigi sekilde terapötik etken moleküller olup, özelligi; AChEI terapötik standart olarak kullaniminda farkli formülasyon içinde tatbik edilebilme yetenegine sahip olmasidir. Istem ?de belirtilen hastaliklarin tedavisinde veya hastaliklardan korunmada Istem 3°te sunulan bulus prulifloksasin molekülü veya Istem4 veya 5”te belirtilen formlari AChE aktivitesine sahip molekül olup, özelligi; farmasötik kompozisyonda gösterilen sunulan bulus prulitloksasin molekülü veya Istem4 veya 5”te belirtilen formlarindan en az bir tanesine sahip olmasidir. Istem 3,te sunulan bulus prulitloksasin molekülü veya Istem4 veya 5*te belirtilen formlari Istem2”de belirtilen hastaliklarin tedavilerinde veya hastaliklardan korunmada AChEl etkisi olup, özelligi; terapötik amaçli supplementer (destekleyici veya katki maddesi] olarak uygulanabilme özelligine sahip olmasidir. Istem 2”de belirtilen hastaliklarin tedavisinde veya korunmasi için farmasötik kompozisyonda prulifloksasin molekülü, prulifloksasin izomer molekül formlari veya bunlarin farmasötik olarak kabul edilen prulifloksasin izomer molekül formlarinin tuz örnekleri en az bir tanesini içermesi olup, özelligi; gidalar içinde Istem13'de belirtilen kullanilabilme yetenegine sahip olmasidir. Istem 3, 4 veya 57teki prulifloksasin molekülü ve formlari AChEl etkisine sahip ilaç olarak kullanlan ilaçlar ile birlikte kullanilmasi olup, özelligi; birlikte kullanildiginda sinerj ik etkinin tek tek oldugundan daha güçlü aktiviteye sahip olmasidir. Istem 3”te sunulan bulus prulitloksasin molekülü veya Istem4 veya 5”te belirtilen formlarinin farmasötik olarak kabul edilebilir bir tasiyici. eksipiyan veya seyreltici içeren bir bilesim içinde mevcut olup, özelligi; bozulmadan moleküllerin tasinabilme ve özelligini koruyabilme yetenegine sahip olmasidir. Sunulan bulus prulitloksasin molekülü veya Istem4 veya 5°te belirtilen formlarinin tasiyicilar ve kaplayicilar kullanilarak hapsedilmesi olup, özelligi; canlilarin vücudunda tasinabilme yetenegine ve ACHEI aktivitesine sahip olmasidir. Istem 3, 4 veya 5°teki prulifloksasin molekülü ve formlarinin ACHEI aktivitesinin korunmasinda ve tasinmasinda önemli olup, özelligi; lstemlö veya l7°de tasiyici olarak belirtilen maddelerin herhangi bir Iiposomi kitosan, quantum dot, kimyasal tasiyicilar ve bunlarin nano-mikro boyuttaki türevlerine sahip olmasidir. Istem 3. 4 veya 57teki prulifloksasin molekülü ve formlarinin ACHEI aktivitesi olup, özelligi; Moleküllerin tedavi edici ajan olarak kullanilan farmasötik kompozisyonu, agiz, nebülize, topikal (bukkal, sublingual, dermal ve intraokuler yolun içinde bulundugu), parenteral (subkutan, intradermal, intra periodontal, intracerobrospiral, intrakas, intravasküler ve intraartikular yolla) veya transdermal yolla uygulanabilme yetenegine sahip olmasidir. Istem 3”te sunulan bulus prulifloksasin molekülü veya Istem4 veya 5”te belirtilen formlarinin lsteml7 veya l9”da belirtildigi gibi vücut içerisinde tasinip Istem2”de belirtilen hastaliklarin tedavisinde kullanilabilir olup, özelligi; tedavi edici moleküller kapsül, draje, toz, krem seklinde uygulanabilme yetenegine sahip olmasidir.CLAIMS . It is an application based on bringing an effective amount of molecules into contact with cells, and its feature is; The molecule or its isomer molecule forms or its pharmaceutically accepted salts have acetyl choline esterase (AChE) inhibitor (AChEI) activity in their natural or synthetic forms. . The common cause of ischemic brain disease, myasthenia gravis, memory defects, neurodegenerative diseases such as alcohol addiction, Alzheimer's disease, Parkinson's disease, myasthena (weakening) of the gastrointestinal smooth muscle or glaucoma or urinary space (bladder) diseases is related to AChE, and its feature is; The main claim is that the said molecules and molecule forms have AChEI activity that can be used in the treatment of diseases. . The substance specified as a molecule in the claim is the prulifloxacin molecule of the present invention, and its feature is; It has AChEI activity. . The invention presented in the claim is a natural or synthetic form of the prulifloxacin molecule or pharmaceutically acceptable salts of the molecule, and its feature is; The natural or synthetic form of the prulifloxacin molecule or the pharmaceutically acceptable salts of the molecule have AChEI activity. . It is the prulifloxacin molecule and pharmaceutical salts of the molecule presented in the claim, and its properties are; hydroxyl groups, sodium, potassium, calcium, potassium salts and hydrobromide salts, amino groups containing basic groups or acidic salts, p-toluene sulfonate (Tosylate), methane sulfonate (mesylate) madelate, lactate, tartrate, citrate, succinate, acetate, dihydrogen phosphate It has hydrogen phosphate, phosphate and hydrosulfate groups. . The prulifloxacin molecule or its forms in claims 1, 4 or 5 can be used in the treatment of diseases in living creatures, and its feature is; In the treatment of neurodegenerative diseases such as ischemic brain disease, myasthenia gravis, memory defects, alcohol addiction, Alzheimer's disease, Parkinson's disease, myasthena (weakening) of the gastrointestinal smooth muscle or glaucoma or urinary space (bladder) diseases, to reduce the effects of the disease or to treat the disorders caused by the disease. The effective amount (dose) of prulifloxacin molecules or pharmaceutically acceptable salts that can be used has AChEI activity. . The cause of the diseases specified in claim 2 in living beings is related to AChE, and its feature is; The prulifloxacin molecule and its forms as in claims 3, 4 or 5 have a therapeutic effect by contacting them with the help of a technique in an effective amount as specified in claim 1. Mammals specified as living creatures in claim 7; human, dog, cat, cow, ox, buffalo, sheep, lamb, ram, goat, poultry; It is in contact with chickens, budgies, pigeons, parrots and turkeys and the therapeutic molecules of the diseases specified in Claim 2, and its feature is; The invention presented in Claim 3 is that the prulifloxacin molecule or its forms specified in Claim 4 or 5 has a therapeutic effect as claimed, due to its AChEI effect on living beings. The treatment of the diseases specified in claim 2 is the large in vivo contact of therapeutic molecules and cells, and its feature is; The prulifloxacin inoleculum and its forms as in claims 3, 4 or 5 have the ability to be used as a therapeutic agent. The invention prulifloxacin molecule presented in Claim 3 or the forms specified in Claim 4 or 5 are therapeutic agents for the diseases specified in Claim 2, as stated in Claim 9, and its feature is; AChEI has the ability to be applied in the same formulation in its therapeutic use. The prulifloxacin molecule presented in Claim 3 or the forms specified in Claim 4 or 5 are therapeutic active molecules for the diseases specified in Claim 2 as stated in Claim 9, and its feature is; AChEI has the ability to be applied in different formulations when used as a therapeutic standard. The invention presented in Claim 3 for the treatment of the diseases specified in Claim or for the prevention of diseases is the prulifloxacin molecule or the molecule with AChE activity in the forms specified in Claim 4 or 5, and its feature is; The present invention shown in the pharmaceutical composition has the prulitloxacin molecule or at least one of its forms specified in claim 4 or 5. The invention prulitloxacin molecule presented in Claim 3 or its forms specified in Claim 4 or 5* has AChEl effect in the treatment of the diseases specified in Claim 2 or in the prevention of diseases, and its feature is; It has the feature of being applied as a supplementer (supporter or additive) for therapeutic purposes. In the pharmaceutical composition for the treatment or protection of the diseases specified in Claim 2, at least one of the prulifloxacin molecule, prulifloxacin isomer molecule forms or salt samples of their pharmaceutically acceptable prulifloxacin isomer molecule forms. Its feature is that it has the ability to be used in foods as stated in Claim 13. The prulifloxacin molecule and its forms in Claim 3, 4 or 57 are used together with drugs that have AChEl effect, and its feature is that when used together, the synergistic effect is stronger than when used individually. The invention presented in Claim 3 is present in a composition containing the prulitloxacin molecule or the forms specified in Claim 4 or 5, a pharmaceutically acceptable carrier, excipient or diluent, and its feature is that it has the ability to transport the molecules without deterioration and maintain their properties. The presented invention is the confinement of the prulitloxacin molecule or its forms specified in Claim 4 or 5 using carriers and coatings, and its feature is; It has the ability to be transported in the body of living things and has ACHEI activity. The prulifloxacin molecule and its forms in claims 3, 4 or 5 are important in protecting and transporting ACHEI activity, and its feature is; The substances specified as carriers in l7° or l7° must not have any Iiposomi chitosan, quantum dot, chemical carriers and their nano-micro sized derivatives. The prulifloxacin molecule and its forms in claims 3, 4 or 57 have ACHEI activity and its feature is; The pharmaceutical composition of the molecules used as a therapeutic agent has the ability to be applied orally, nebulized, topically (including buccal, sublingual, dermal and intraocular), parenteral (subcutaneous, intradermal, intraperiodontal, intraceroboral, intramuscular, intravascular and intraarticular) or transdermally. is to have. The invention prulifloxacin molecule presented in Claim 3 or its forms specified in Claim 4 or 5 can be carried within the body as specified in Claim 7 or 19 and used in the treatment of the diseases specified in Claim 2, and its feature is; Therapeutic molecules have the ability to be applied in the form of capsules, dragees, powders and creams.
TR2021/022265A 2020-12-31 2021-12-31 Acetylcholinesterase Inhibitory Activity of Salt Samples of Prulifloxacin Molecule, Prulifloxacin Isomer Molecule Forms, or Their Pharmaceutically Accepted Prulifloxacin Isomer Molecule Forms TR2021022265A2 (en)

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