TR202021399A2 - USE OF BENIDIPIN FOR THE TREATMENT OF EPILEPSY - Google Patents
USE OF BENIDIPIN FOR THE TREATMENT OF EPILEPSY Download PDFInfo
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- TR202021399A2 TR202021399A2 TR2020/21399A TR202021399A TR202021399A2 TR 202021399 A2 TR202021399 A2 TR 202021399A2 TR 2020/21399 A TR2020/21399 A TR 2020/21399A TR 202021399 A TR202021399 A TR 202021399A TR 202021399 A2 TR202021399 A2 TR 202021399A2
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- 206010015037 epilepsy Diseases 0.000 title claims abstract description 37
- 238000011282 treatment Methods 0.000 title claims abstract description 37
- 229960004916 benidipine Drugs 0.000 claims abstract description 33
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
Bu buluş; epilepsi hastalığının tedavisine yönelik bir ilacın üretiminde benidipinin ve/veya bunun farmasötik olarak kabul edilebilir bir tuzunun kullanımı ile ilgilidir.This invention; It relates to the use of benidipine and / or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of epilepsy.
Description
TARIFNAME BENIDIPININ EPILEPSI HASTALIGININ TEDAVISINE Y'ONELIK KULLANIMI Teknik Alan Bu bulus; halihazirda hipertansiyon tedavisinde yaygin olarak kullanilmakta olan benidipin molekülünün anti-epileptik ve nöroprotektif etkinliginden yararlanilarak epilepsi hastaliginin tedavisine yönelik bir ilacin üretiminde kullanimi ile ilgilidir. DESCRIPTION ONE USE OF BENIDIPIN FOR THE TREATMENT OF EPILEPSIAL DISEASE Technical Area This invention; Benidipine, which is currently widely used in the treatment of hypertension epilepsy by taking advantage of the anti-epileptic and neuroprotective activity of the molecule. It relates to its use in the manufacture of a drug for the treatment of disease.
Teknigin Bilinen Durumu Kimyasal ve fiziksel uyarilara duyarli bir yapiya sahip olan hücreler, hücre membraninda yer alan ve kanal adi verilen özgün yapilar araciligi ile çesitli iyonlarin hücre içine ya da disina geçisine olanak saglamaktadir. iyonlarin geçisi hücrenin temel islevlerini göstermesi bakimindan önem tasimakta ve belli fizyolojik etkilerin ortaya çikmasina neden olmaktadir. Naî K*, Ca”, Cl* vb. gibi iyonlarin geçisine olanak saglayan bu kanallar iyonlara özgü olup bir baska iyon geçisine izin vermemektedirler. iyonlarin bu hareketleri çesitli biyolojik olaylarin ortaya çikisina neden olmaktadir. State of the Art Cells that are sensitive to chemical and physical stimuli are located in the cell membrane. Various ions are transferred into the cell or through the unique structures called channels. It allows the passage to the outside. the passage of ions performs the basic functions of the cell. It is important in terms of showing and causing certain physiological effects to occur. is happening. Naî K*, Ca”, Cl* etc. These channels, which allow the passage of ions such as They are specific to ions and do not allow another ion to pass. These movements of ions causes the emergence of various biological events.
Ornegin hücre içindeki kalsiyum iyonlari kasilma, salgilama ve nöral etkiler gibi fizyolojik olaylarin düzenlenmesinden sorumludur. Ancak diger taraftan kalsiyum iyonlarinin kendine özgü kanallar araciligiyla hücre içine girisi damar düz kasi ve kalp kasinda kasilmalara yol açarak tansiyonun yükselmesine neden olmaktadir. Bu nedenle, hücre içine kalsiyumun girisinin engellenmesi angina pektoris, hipertansiyon, vazospazm, atriyal fibrilasyon, miyokardiyal iskemi, periferik hastaliklar ve diger birçok hastaligin tedavisinde önemli bir yaklasimdir. Sonuç olarak, kalsiyum kanallarinin bloke edilerek bu özellikteki ilaçlarin tedavide kullanimlari önem kazanmistir. For example, calcium ions in the cell are physiologically affected by contraction, secretion and neural effects. Responsible for organizing events. On the other hand, calcium ions Its entry into the cell through its specific channels is in vascular smooth muscle and cardiac muscle. it causes contractions and increases blood pressure. Therefore, the cell Inhibition of calcium influx into angina pectoris, hypertension, vasospasm, atrial fibrillation, myocardial ischemia, peripheral diseases and many other diseases It is an important approach. As a result, by blocking the calcium channels, The use of drugs in treatment has gained importance.
Kalsiyum kanallarini bloke eden moleküllerin damar düz kaslarini ve kalbin kasilmasini etkileyebilecegi ilk kez 1960*Ii yillarda dikkati çekmistir. O tarihten günümüze kalsiyum kanal blokerleri (KKB) özellikle hipertansiyon tedavisinde önemli ilaç gruplarindan biri haline gelmistir' Kalsiyum kanal blokerleri, nöron ya da kas hücreleri gibi uyarilabilir hücrelerde bulunan voltaj-bagimli kalsiyum kanallarini kapatarak, hücre disindan kalsi- yumun girisini inhibe eder ve hücre içi kalsiyum düzeyini düsürürler. Günümüzde klinik kullanim için onay almis KKB'Ier kimyasal açidan; dihidropridinler, fenilalkilaminler ve benzodiazepinler olmak üzere üç alt grupta degerlendirilebilirler. Molecules blocking calcium channels inhibit vascular smooth muscle and contraction of the heart. It was noticed for the first time in the 1960s. Since then calcium channel blockers (CCBs) are one of the important drug groups especially in the treatment of hypertension. Calcium channel blockers can be stimulated like neurons or muscle cells by closing voltage-dependent calcium channels in cells, They inhibit the entry of calcium and lower the intracellular calcium level. Today, clinical KKB's approved for use in terms of chemicals; dihydropyridines, phenylalkylamines and They can be evaluated in three subgroups as benzodiazepines.
Farkli ilaç gruplarindan olusan kalsiyum kanal blokerlerinin ilk örnegi olan fenilalkilamin türevi verapamilin 1960ilarda tedaviye ß-adrenoreseptör blokeri olarak girmis sonrasinda ise, 1970'Ierin basinda kalsiyum kanal modülatör etkisi saptanmistir. Kalsiyum kanal blokerlerinin önemli bir üyesi olan benzodiazepin türevi diltiazem de hücre membraninda voltaja bagli kalsiyum kanallarini etkileyerek kalsiyum antagonist etki göstermektedir. Phenylalkylamine, the first example of calcium channel blockers consisting of different drug groups Its derivative verapamil was introduced in the 1960s as a ß-adrenoreceptor blocker. On the other hand, the calcium channel modulator effect was detected in the early 1970s. calcium channel Diltiazem, a benzodiazepine derivative, is an important member of the cell membrane It acts as a calcium antagonist by affecting voltage-dependent calcium channels.
Diltiazem voltaja bagli L kanallari araciligiyla transmembran kalsiyum girisini doza bagli olarak inhibe eden önemli bir ilaçtir Kalsiyum kanal blokerlerinin en önemli üyesi türevi ilaçlar, günümüzde angina pektoris ve hipertansiyon tedavisinde en çok kullanilan ilaçlar olmuslardir. 1,4-DHP=Ierin ilk sentezleri 1882'de Hantzsch tarafindan bildirilmis, grubun prototipi olan nifedipin Adalat ticari adiyla 1975 yilinda Bayer tarafindan Almanyaida piyasaya sunulmustur. 1,4-DHP türevi ilaçlardan bazilari; nifedipin, amlodipin, azelnidipin, klinidipin, klevidipin, nikardipin, benidipin, manidipin, flordipin, felodipin olarak sayilabilir. Diltiazem dose-dependently inhibits transmembrane calcium influx through voltage-dependent L channels. It is an important drug that inhibits The most important member of calcium channel blockers derivative drugs, Today, the most used drugs in the treatment of angina pectoris and hypertension they have been. The first synthesis of 1,4-DHP=Is was reported by Hantzsch in 1882. Nifedipine, the prototype of which was introduced in Germany in 1975 by Bayer under the trade name Adalat. has been put on the market. Some of the 1,4-DHP derivative drugs; nifedipine, amlodipine, azelnidipine, clinidipine, clevidipine, nicardipine, benidipine, manidipine, flordipine, felodipine.
Söz konusu moleküller voltaj-bagimli kalsiyum kanallarinin çogunlukla L-tipine baglanirlar. These molecules bind mostly to the L-type of voltage-dependent calcium channels.
Yakin zamanda yapilan çalismalar, bazi kalsiyum kanal blokerlerinin N ve T-tipi kanallara da baglandigini göstermistir. Bunlardan N-tipi kanallar sempatik sinir uçlarinda, T-tipi kanallar ise kardiyak sinus nodu ile afferent ve efferent arteriyollerde bulunur. Bu iki tip kanalin blokaji, glomerüler kapiller basincin azalmasina, renin-anjiotensin-aldosteron sisteminin ve sempatik sinir sisteminin stabilizasyonuna neden olur. Ozellikle yeni jenerasyon kalsiyum kanal blokerleri, renoprotektif, vasküler endotel koruyucu etki ve kardiyoprotektif etkiler gibi pleiotropik etkiler olarak tanimlananan etkilere sahiptirler. Recent studies have shown that some calcium channel blockers have N- and T-type channels. also showed that it is connected. Of these, N-type channels are located in sympathetic nerve endings, T-type channels channels are found in the cardiac sinus node and afferent and efferent arterioles. These two types blockage of the duct, decrease in glomerular capillary pressure, renin-angiotensin-aldosterone Causes stabilization of the nervous system and sympathetic nervous system. especially new generation calcium channel blockers, renoprotective, vascular endothelial protective effect and They have effects described as pleiotropic effects, such as cardioprotective effects.
Uçüncü jenerasyon 1,4-DHP türevi bir kalsiyum kanal blokeri olan benidipin, günümüzde hipertansiyon tedavisinde yaygin olarak kullanilmakta olan ve L, N ve T tipi tüm kalsiyum kanallarina etkinligi olan bir kalsiyum kanal blokeridir. Anti-hipertansif endikasyon ile kullaniminda gözlemlenen düsük yan etki insidansi ve düsük maliyeti dikkat çekicidir. sayili patent dokümaninda bahsedilmektedir. Söz konusu bilesimin spesifik parçacik boyutunda kristalimsi benidipin hidroklorür ve polivinil alkol içerdigi belirtilmistir. Benidipine, a third-generation 1,4-DHP-derived calcium channel blocker, is currently L, N, and T-type calcium supplements are widely used in the treatment of hypertension. It is a calcium channel blocker with activity on the channels. With anti-hypertensive indication The low incidence of side effects and low cost observed in its use are remarkable. It is mentioned in the patent document no. The specific particle of the composition in question It was stated that it contains crystalline benidipine hydrochloride and polyvinyl alcohol in size.
Ozellikle yeni jenerasyon KKB'Ierinin antihipertansif ve kardiyovasküler etkilerinin yani sira baska pleiotropik etkileri de mevcut teknikte arastirilmaktadir. Ornegin Polat ve Uzun'a ait 2013 tarihli bir yayinda kalsiyum kanal blokerlerinin deri hastaliklarinda kullanimi üzerinde durulmustur. Buna göre 'Özellikle nifedipin, diltiazem, verapamil ve bunlarin kombine kullanimlarinin dermatolojik hastaliklarda ve bilhassa flap cerrahisinde umut verici oldugu sonucuna varilmistir. In addition to the antihypertensive and cardiovascular effects of new generation CCBs, other pleiotropic effects are also explored in the current art. For example, belonging to Polat and Uzun In a 2013 publication, on the use of calcium channel blockers in skin diseases has been stopped. Accordingly, 'especially nifedipine, diltiazem, verapamil and their combination Its use is promising in dermatological diseases and especially in flap surgery. conclusion has been reached.
Diger taraftan Canbolat ve arkadaslarina ait 2018 tarihli bir makalede dihidropiridin türevi bazi bilesiklerin endotel koruyucu, antioksidan ve antiinflamatuvar, antiataerosklerotik, serebrovasküler, renal ve dermal etkilerinin yani sira migren, depresyon, epilepsi ve kanser tedavisindeki etkileri arastirilmistir. Söz konusu çalismada spesifik olarak nifedipin, nimodipin ve amlodipin moleküllerinin epilepsi tedavisinde antikonvülsan etkileri oldugu kaydedilmistir. Bunun yani sira Ierkanidipinin olumlu nöroprotektif etkisi nedeniyle, konvülsiyonlarin tedavisinde, potansiyel bir aday olabilecegi vurgulanmaktadir. Ancak bunlarin epilepsi tedavisinde ne sekilde kullanilacagina dair herhangi bir detaya yer verilmemistir. On the other hand, in a 2018 article by Canbolat et al., the dihydropyridine derivative some compounds are endothelial protective, antioxidant and anti-inflammatory, antiatherosclerotic, cerebrovascular, renal and dermal effects as well as migraine, depression, epilepsy and Its effects in cancer treatment have been investigated. In the study in question, specifically nifedipine, It has been reported that nimodipine and amlodipine molecules have anticonvulsant effects in the treatment of epilepsy. has been recorded. In addition, due to the positive neuroprotective effect of Iercanidipine, It is emphasized that it can be a potential candidate in the treatment of convulsions. However No details on how they might be used to treat epilepsy. not given.
Bagirici ve arkadaslarina ait diger bir makalede ise kalsiyum kanal blokerlerinin epileptik aktiviteye etkisi arastirilmistir. Söz konusu yayin kapsaminda dihidropiridin türevlerinden nimodipin 4 farkli doz ve 5 farkli epilepsi modeli üzerinde çalisilmis, nimodipinle yapilan ön tedavinin, aminofilin+elektrosok ve aminofilin+pentilenetetrazol ile indüklenen epilepsiyi pentilenetetrazolle olusturulan nöbetlere karsi anlamli antikonvülsan etki göstermistir. In another article by Bagirici et al. The effect on activity was investigated. Within the scope of the said publication, dihydropyridine derivatives 4 different doses of nimodipine and 5 different epilepsy models were studied. epilepsy induced by aminophylline + electroshock and aminophylline + pentylenetetrazole. It showed a significant anticonvulsant effect against seizures induced by pentylenetetrazole.
Diger taraftan noradrenalin, asetilkolin, 5-hidroksitriptamin, aspartat ve glutamatin serbestlenmesinin arttigi durumlarin ise nifedipin tarafindan önlendigi öne sürülmüstür. On the other hand, noradrenaline, acetylcholine, 5-hydroxytryptamine, aspartate and glutamate It has been suggested that nifedipine releases increased states are prevented by nifedipine.
Ancak yine benzer sekilde spesifik olarak bir KKB'nin epilepsi hastaliginin tedavisinde kullanimina yönelik detayli bir bilgilendirme bulunmamaktadir. However, similarly, specifically in the treatment of a CCB's epilepsy disease. There is no detailed information about its use.
Epilepsi kronik bir hastalik olup, beyinde bulunan nöronlarda ani ve kontrolsüz bosalmalar olarak tanimlanabilir. Epilepsi krizi geçiren hastada istemsiz kasilmalar, duyusal degisiklikler ve bilinç degisiklikleri meydana gelir. Epilepsi bilinenin aksine oldukça tehlikeli bir hastalik olup hastanin hayat standartlarini düsürmesinin yaninda mortaliteyi de artirmaktadir. Depresyon, anksiyete, demans, migren, kalp hastaligi, peptik ülser ve artrit gibi komorbiditeler epilepsili kisilerde genel popülasyondan sekiz kat daha sik görülmektedir. Epilepsi tedavisinde kullanilan mevcut ilaçlar, sadece atak kontrolünü hedeflemekte, epilepsiye bagli olusan komplikasyon ve ileride ortaya çikacak patolojik problemleri önleme konusunda etkinlikleri bulunmamaktadir. Mevcut anti-epileptik ilaçlar, epileptik ataklari önlemede ancak 2/3 oraninda basarili olabilmekte, hastalarin %30iunda basarisiz olmaktadirlar. Epilepsy is a chronic disease that causes sudden and uncontrolled release of neurons in the brain. can be defined as Involuntary contractions, sensory changes and changes in consciousness occur. Contrary to what is known, epilepsy is quite dangerous. It is a disease that reduces the patient's life standards as well as mortality. is increasing. Depression, anxiety, dementia, migraine, heart disease, peptic ulcer and arthritis Comorbidities such as epilepsy are eight times more common in people with epilepsy than in the general population. is seen. Existing drugs used in the treatment of epilepsy only control attacks. It aims at the complications of epilepsy and future pathological There are no activities to prevent problems. existing anti-epileptic drugs, It can be successful in preventing epileptic attacks only at the rate of 2/3, and in 30% of patients they fail.
Yukarida verilen örneklerden de görülecegi üzere, kalsiyum kanal blokerlerinin hem yapisal hem de fonksiyonel olarak birbirinden oldukça farklilasmalari, bunlarin olasi kullanim alanlarini da etkilemektedir. Ornegin dihidropiridin türevi KKB!Ier çogunlukla damar genisletici özellik gösterirken, dihidropiridin türevi olmayan KKB'ler negatif inotropik etki göstermeye yatkindirlar. Hem siniflar arasi farklilik hem de bu siniflar altinda yer alan moleküllerin kimyasal yapilarindan ileri gelen farkliliklar söz konusu KKB'Iere kendi içlerinde bireysel nitelikler kazanmaya itmektedir. As can be seen from the examples given above, calcium channel blockers are both structurally and functionally quite different from each other, these are possible It also affects the areas of use. For example, the dihydropyridine derivative CCBs are mostly CCBs without dihydropyridine derivatives show vasodilating properties, whereas CCBs are negative inotropic are prone to influence. Both the difference between classes and the The differences arising from the chemical structures of the molecules may be related to the KKBs in question. pushes them to acquire individual qualities.
Mevcuttaki uygulamalar incelendiginde; kalsiyum kanal blokerlerinin, özellikle de binedipin molekülünün, spesifik olarak epilepsi tedavisinde kullanimina yönelik olarak gelistirilen bir ilaç ya da kürün bulunmadigi görülmektedir. Diger taraftan mevcut teknikte uygulanan epilepsi tedavilerinin yalnizca atak kontrolünü hedefledigi ve epilepsiye bagli komplikasyonlarda etkisiz kaldiklari da göz önüne alindiginda, KKBJIerin veya bunlarin diger etkin maddelerle kombinasyonlarinin anti-epileptik ve nöroprotektif fonksiyonlarindan etkin sekilde yararlanildigi yöntemlere halen ihtiyaç duyulmaktadir. When the existing applications are examined; calcium channel blockers, especially binedipin molecule developed specifically for use in the treatment of epilepsy. It is seen that there is no medicine or cure. On the other hand, applied in the current technique Epilepsy treatments target only attack control and Considering that they are ineffective in complications, CCBJs or their Anti-epileptic and neuroprotective effects of combinations with other active substances There is still a need for methods that make effective use of its functions.
Bulusun Kisa Açiklamasi Mevcut bulus; yukarida bahsedilen gereksinimleri karsilayan, tüm dezavantajlari ortadan kaldiran ve ilave bazi avantajlar getiren, benidipinin epilepsi hastaliginin tedavisine yönelik kullanimi ile ilgilidir. Brief Description of the Invention The present invention; meeting the above-mentioned requirements, eliminating all the disadvantages Benidipine to the treatment of epilepsy disease, which removes and brings some additional advantages. related to its use.
Bulusun öncelikli amaci; kalsiyum kanal blokeri içerisinden spesifik olarak seçilen benidipinin anti-epileptik ve nöroprotektif etkinliginden faydalanmaktir. The primary purpose of the invention is; Specifically selected from the calcium channel blocker benefit from the anti-epileptic and neuroprotective effects of benidipine.
Bulusun bir diger amaci; benidipin molekülünün epilepsinin tedavisinde kullanilmak üzere bir dozaj formu içerisinde kullanilmasidir. Another purpose of the invention; Benidipine molecule for use in the treatment of epilepsy used in a dosage form.
Bulusun diger bir amaci, benidipinin en az bir diger anti-epileptik etkin madde ile kombinasyonunu içeren oral dozaj formlari gelistirmektir. Another object of the invention is to combine benidipine with at least one other anti-epileptic active substance. To develop oral dosage forms containing the combination of
Bulusun bir diger amaci; kronik bir hastalik olan epilepsinin semptomatik tedavisinin yani sira epilepsinin sebep oldugu nörolojik ve bilissel komplikasyonlarin tedavisinde de kullanima uygun bir dozaj formunun gelistirilmesidir. Another purpose of the invention; symptomatic treatment of epilepsy, which is a chronic disease. It is also used in the treatment of neurological and cognitive complications caused by epilepsy. development of a dosage form suitable for use.
Bulusun bir diger amaci; epilepsi tedavisinde kullanima uygun, düsük maliyet ve kolay ulasilabilirlik avantajlarini da beraberinde getiren bir dozaj formunun gelistirilmesidir. Another purpose of the invention; low cost and easy to use in the treatment of epilepsy It is the development of a dosage form that brings with it the advantages of accessibility.
Yukarida anlatilan amaçlarin yerine getirilmesi için, bulus epilepsi hastaliginin tedavisine yönelik bir ilacin üretiminde benidipinin ve/veya bunun farmasötik olarak kabul edilebilir bir tuzunun kullanimidir. To fulfill the above-described purposes, the invention is devoted to the treatment of epilepsy. Benidipine and/or a pharmaceutically acceptable agent thereof in the manufacture of a medicine for the use of salt.
Bulusun yapisal ve karakteristik 'Özellikleri ve tüm avantajlari asagida verilen detayli açiklama sayesinde daha net olarak anlasilacaktir. Bu nedenle degerlendirmenin, detayli açiklama göz önüne alinarak yapilmasi gerekmektedir. The structural and characteristic features of the invention and all its advantages are detailed below. It will be clearer with the explanation. Therefore, detailed evaluation must be made taking into account the description.
Bulusun Detayli Açiklamasi Bu detayli açiklamada, bulus konusu benidipinin epilepsi hastaliginin tedavisine yönelik kullanimi, konunun daha iyi anlasilmasina yönelik olarak ve hiçbir sinirlayici etki olusturmayacak sekilde açiklanmaktadir. Detailed Description of the Invention In this detailed description, the subject of the invention is the treatment of benidipine epilepsy. its use is intended for a better understanding of the subject and has no limiting effect. described in a way that does not constitute.
Bulus; epilepsi hastaliginin tedavisine yönelik bir ilacin üretiminde benidipinin ve/veya bunun farmasötik olarak kabul edilebilir bir tuzunun kullanimidir. Meet; Benidipine and/or is the use of a pharmaceutically acceptable salt thereof.
SÖZ konusu molekülün kimyasal adi 5-0-[(3R)-1-benzilpiperidin-3-il] 3-O-metil (4R)-2,6- dimetiI-4-(3-nitr0fenil)-1,4-dihidropiridin-3,5-dikarboksilat seklinde olup kimyasal formülü asagidaki Formül 1 ile verilmistir. The chemical name of the molecule in question is 5-O-[(3R)-1-benzylpiperidin-3-yl] 3-O-methyl (4R)-2,6- It is in the form of dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate and its chemical formula is given by Formula 1 below.
Formül 1. Benidipin Burada epilepsi hastaligi ifadesi ile kastedilen, epilepsi nöbetleri sirasinda görülen semptomatik belirtiler (kasilmalar, kisa süreli bilissel kayip vb.) ve bu epilepsi nöbetlerinin sebep oldugu uzun süreli nörodejeneratif ve bilissel komplikasyonlardir. Burada bahsi geçen tedavi ifadesi epilepsinin küratif, palyatif ve profilaktik tedavisini içermektedir. Bu etki benidipin molekülünün eszamanli olarak anti-epileptik ve nbroprotektif etkinlik Bulusun yeniligi benidipinin, hipertansiyon hastaliginin tedavisinden bagimsiz olarak farkli bir hastaligin tedavisinde endikasyon gbstermesinden ileri gelmektedir. Formula 1. Benidipine What is meant by the term epileptic disease here is that seen during epileptic seizures. symptomatic symptoms (convulsions, short-term cognitive loss, etc.) and They are long-term neurodegenerative and cognitive complications caused by bet here The term treatment mentioned includes the curative, palliative and prophylactic treatment of epilepsy. This effect of the benidipine molecule with simultaneous anti-epileptic and neuroprotective activity The novelty of the invention is that benidipine is different from the treatment of hypertension disease independently. It comes from the fact that it shows an indication in the treatment of a disease.
Bulusun bir uygulamasinda, bahsi geçen ilaç epilepsi tedavisinde oral, bukal veya dilalti uygulamalara uygundur. Burada bahsi geçen ilaç; tablet, çok katmanli tablet, agizda dagilan tablet, mini tablet, pellet, bukal tablet, dilalti tablet, efervesan tablet, çabuk salim saglayan tablet, modifiye salim saglayan tablet, film kapli tablet, midede dagilan tablet, kapsül, çoklu granül, toz, jel, film, solüsyon, süspansiyon dozaj formlarini içeren gruptan seçilmektedir. In one embodiment of the invention, the aforementioned drug is administered orally, buccally or sublingually in the treatment of epilepsy. suitable for applications. The drug mentioned here; tablet, multilayer tablet, oral Disintegrating tablet, mini tablet, pellet, buccal tablet, sublingual tablet, effervescent tablet, immediate release release tablet, modified release tablet, film-coated tablet, gastric disintegrating tablet, capsule, multiple granule, powder, gel, film, solution, suspension dosage forms is selected.
Bulusun bir diger uygulamasinda, bahsi geçen ilaç epilepsi tedavisinde parenteral uygulamalara uygundur. Burada bahsi geçen ilaç; intrakavern'oz, intravenöz, intra- arteriyel, intraperitoneal, intratekal, intraventriküler, intraüretral, intrastern, intrakranial, intramüsküler veya subkutan olarak infüzyon veya ignesiz enjeksiyon teknikleri ile uygulanabilir. In another embodiment of the invention, the aforementioned drug is used parenterally in the treatment of epilepsy. suitable for applications. The drug mentioned here; intracavernous, intravenous, intra- arterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscularly or subcutaneously by infusion or needleless injection techniques applicable.
Bulusun bir diger uygulamasinda ise bahsi geçen ilaç epilepsi tedavisinde intranasal veya inhalasyon yoluyla uygulamalara uygundur. Bu uygulamaya göre benidipin; kuru toz inhaler cihazi, aerosol sprey cihazi, pompa, atomizer veya nebulizatbr kullanilarak uygulanmaktadir. In another application of the invention, the aforementioned drug is used intranasally or in the treatment of epilepsy. Suitable for administration by inhalation. According to this application, benidipine; dry powder using inhaler device, aerosol spray device, pump, atomizer or nebulizer is being implemented.
Bulusun tercih edilen uygulamasina göre; benidipin tek basina veya farmasötik olarak kabul edilebilir en az bir yardimci madde ile beraber uygulanmaktadir. Burada bahsi geçen yardimci madde; baglayicilar, seyrelticiler, dagiticilar, dolgu maddeleri, lubrikantlar, glidanlar, propelantlari içeren gruptan seçilmektedir. According to the preferred embodiment of the invention; Benidipine alone or as a pharmaceutical It is applied together with at least one acceptable excipient. bet here the preceding excipient; binders, diluents, dispersants, fillers, lubricants, glidants are selected from the group consisting of propellants.
Bulusun tercih edilen uygulamasinda göre benidipin oral olarak epilepsi tedavisine yönelik kullanilmaktadir. Bulusun en tercih edilen haliyle, benidipin tablet formunda kullanilmaktadir. According to the preferred embodiment of the invention, benidipine is administered orally for the treatment of epilepsy. is used. Most preferably, benidipine is in tablet form. is used.
Bulusun tercih edilen uygulamasinda, benidipinin epilepsi hastaliginin tedavisine y'onelik kullaniminda tercih edilen günlük dozaj 2-4 mg/kg araliginda degismektedir. In the preferred embodiment of the invention, benidipine is used for the treatment of epilepsy. The preferred daily dosage in its use varies between 2-4 mg/kg.
Bir uygulamaya göre, benidipin içeren dozaj formu 2 mg/kg veya 4 mg/kg miktarinda benidipin içermektedir. Buna göre benidipin içeren dozaj formu, epilepsi tedavisinde, hastaligin siddetine göre günde bir, iki veya üç defada hastaya uygulanabilmektedir. According to one embodiment, the dosage form containing benidipine is at an amount of 2 mg/kg or 4 mg/kg. Contains benidipine. Accordingly, the dosage form containing benidipine is used in the treatment of epilepsy. It can be applied to the patient once, twice or three times a day, depending on the severity of the disease.
Bulusun bir uygulamasinda, benidipin bir diger anti-epileptik etkin madde ile birlikte kombine sekilde epilepsi tedavisinde kullanilmaktadir. Burada bahsi geçen anti-epileptik ajan tercihen valproik asittir. Bulusun tercih edilen bu uygulamasinda göre; benidipin ve valproik asit hastaya simultane olarak, ayri ayri veya sirali olarak; tek bir dozaj formunda veya ayri dozaj formlarinda uygulanabilmektedir. In one embodiment of the invention, benidipine is combined with another anti-epileptic active substance. It is used in combination in the treatment of epilepsy. The anti-epileptic the agent is preferably valproic acid. According to this preferred embodiment of the invention; Benidipine and valproic acid to the patient simultaneously, separately or sequentially; in a single dosage form or in separate dosage forms.
Bulusun tercih edilen uygulamasinda, benidipin veya farmasötik olarak kabul edilebilir bir tuzu ve valproik asit tek bir tablet dozaj formu içerisinde epilepsi tedavisine yönelik olarak hastaya uygulanmaktadir. In the preferred embodiment of the invention, benidipine or a pharmaceutically acceptable salt and valproic acid in a single tablet dosage form for the treatment of epilepsy applied to the patient.
Bulus kapsaminda yapilan çalismalar, benidipinin tek basina kullaniminin veya valproik asit ile kombine kullaniminin anlamli sekilde anti-epileptik etkinlik gösterdigini ortaya koymustur. Biyokimyasal analizde beyin hemisferinde IL-1 ve TNF-alfa düzeylerini azalttigini ve anlamli anti-inflamatuvar etkinlik belirlenmistir. Dahasi valproik asit ile kombine edilen benidipinin 4mg/kg dozunun, saglikli gruba yakin bir düzeyde n'oroproteksiyon sagladigi saptanmistir. Studies carried out within the scope of the invention have shown that the use of benidipine alone or valproic acid It has been revealed that combined use with acid shows significant anti-epileptic activity. has put. Biochemical analysis of IL-1 and TNF-alpha levels in the brain hemisphere. and significant anti-inflammatory activity was determined. Moreover, with valproic acid 4mg/kg dose of the combined benidipine was at a level close to the healthy group. It has been determined that it provides neuroprotection.
Benidipinin epilepsi tedavisine yönelik kullanimi ile, mevcut teknikte epilepsi tedavisinde kullanilan ilaçlarla kiyaslandiginda yüksek anti-epileptik etkinligin yani sira nbroprotektif etkinlik de gösteren, maliyeti düsürülmüs ve ulasilabilirligi arttirilmis yeni dozaj formlarinin profilaktik tedavisine yönelik bir ilacin üertiminde kullanimi ile epilepsiye bagli komplikasyonlarin da önüne geçen tedavilerin önünü açmaktadir. With the use of benidipine for the treatment of epilepsy, in the current art, in the treatment of epilepsy. Compared to the drugs used, it has high anti-epileptic efficacy as well as nbroprotective of new dosage forms that also show efficacy, reduced cost and increased availability. associated with epilepsy with its use in the manufacture of a drug for the prophylactic treatment paves the way for treatments that also prevent complications.
Claims (11)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2020/21399A TR202021399A2 (en) | 2020-12-23 | 2020-12-23 | USE OF BENIDIPIN FOR THE TREATMENT OF EPILEPSY |
| PCT/TR2021/051404 WO2022139753A2 (en) | 2020-12-23 | 2021-12-14 | Use of benidipine for the treatment of epilepsy disease |
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| Application Number | Priority Date | Filing Date | Title |
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| TR2020/21399A TR202021399A2 (en) | 2020-12-23 | 2020-12-23 | USE OF BENIDIPIN FOR THE TREATMENT OF EPILEPSY |
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| TR202021399A2 true TR202021399A2 (en) | 2021-01-21 |
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| US6011035A (en) * | 1998-06-30 | 2000-01-04 | Neuromed Technologies Inc. | Calcium channel blockers |
| JP2000103736A (en) * | 1998-07-31 | 2000-04-11 | Takeda Chem Ind Ltd | Vasopermeable sthenia suppressing agent |
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