TR2021009613T - A NEW DRUG COMBINATION PROVIDING LONG-TERM ANESTHESIA - Google Patents
A NEW DRUG COMBINATION PROVIDING LONG-TERM ANESTHESIAInfo
- Publication number
- TR2021009613T TR2021009613T TR2021/009613 TR2021009613T TR 2021009613 T TR2021009613 T TR 2021009613T TR 2021/009613 TR2021/009613 TR 2021/009613 TR 2021009613 T TR2021009613 T TR 2021009613T
- Authority
- TR
- Turkey
- Prior art keywords
- pharmaceutical combination
- combination
- anesthesia
- ropivacaine
- clonidine
- Prior art date
Links
- 206010002091 Anaesthesia Diseases 0.000 title claims description 17
- 230000037005 anaesthesia Effects 0.000 title claims description 17
- 230000007774 longterm Effects 0.000 title description 3
- 239000002547 new drug Substances 0.000 title 1
- ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 claims abstract description 20
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229960002896 clonidine Drugs 0.000 claims abstract description 20
- 229960001549 ropivacaine Drugs 0.000 claims abstract description 20
- 229960002537 betamethasone Drugs 0.000 claims abstract description 19
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims abstract description 18
- 238000001356 surgical procedure Methods 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 150000004677 hydrates Chemical class 0.000 claims abstract description 8
- 239000006201 parenteral dosage form Substances 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 13
- VSHFRHVKMYGBJL-CKUXDGONSA-N (S)-ropivacaine hydrochloride hydrate Chemical compound O.[Cl-].CCC[NH+]1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C VSHFRHVKMYGBJL-CKUXDGONSA-N 0.000 claims description 8
- 208000004550 Postoperative Pain Diseases 0.000 claims description 7
- 229960003691 ropivacaine hydrochloride monohydrate Drugs 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000012458 free base Substances 0.000 claims description 6
- 230000000399 orthopedic effect Effects 0.000 claims description 6
- 229960002925 clonidine hydrochloride Drugs 0.000 claims description 5
- 238000001802 infusion Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- ZNIFSRGNXRYGHF-UHFFFAOYSA-N Clonidine hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1NC1=NCCN1 ZNIFSRGNXRYGHF-UHFFFAOYSA-N 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- 238000013265 extended release Methods 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 239000002502 liposome Substances 0.000 claims description 3
- 239000003094 microcapsule Substances 0.000 claims description 3
- 239000002088 nanocapsule Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 238000002692 epidural anesthesia Methods 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000002694 regional anesthesia Methods 0.000 claims description 2
- 229960001813 ropivacaine hydrochloride Drugs 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 238000002693 spinal anesthesia Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008215 water for injection Substances 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 abstract description 19
- 230000036407 pain Effects 0.000 abstract description 17
- 210000005036 nerve Anatomy 0.000 abstract description 6
- 238000002648 combination therapy Methods 0.000 abstract description 3
- 230000000694 effects Effects 0.000 description 20
- 239000003589 local anesthetic agent Substances 0.000 description 15
- 229960005015 local anesthetics Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 239000000730 antalgic agent Substances 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- 239000003470 adrenal cortex hormone Substances 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 229940035674 anesthetics Drugs 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000007542 Paresis Diseases 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
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- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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Abstract
Mevcut buluş, ağrıyı kontrol etmek ve hafifletmek için bir yeni kombinasyon tedavisi ile ilgilidir. Daha da özel olarak buluş, motor sinir blokajına neden olmadan ameliyattan önce veya sonra uygulanabilen parenteral dozaj formunda bir yeni uzun etkili farmasötik kombinasyon ile ilgilidir. Mevcut buluşa göre farmasötik kombinasyon, ropivakain, klonidin, betametazon veya bunların farmasötik olarak uygun tuzlarını ve hidratlarını ihtiva etmektedir.The present invention relates to a novel combination therapy for controlling and relieving pain. More particularly, the invention relates to a novel long-acting pharmaceutical combination in parenteral dosage form that can be administered before or after surgery without causing motor nerve blockade. The pharmaceutical combination according to the present invention contains ropivacaine, clonidine, betamethasone or pharmaceutically acceptable salts and hydrates thereof.
Description
TARiFNAME BIR YENI UZUN SÜRELI ANESTEZI SAGLAYAN iLAç KOMBINASYONU Bulusun Ilgili Oldugu Alan Mevcut bulus, agriyi kontrol etmek ve hafifletmek için bir yeni kombinasyon tedavisi ile ilgilidir. DESCRIPTION A NEW COMBINATION OF DRUGS PROVIDING LONG-TERM ANESTHESIA Field to which the invention relates The present invention relates to a novel combination therapy for controlling and relieving pain.
Daha da özel olarak bulus, ameliyattan önce veya sonra uygulanabilen bir parenteral dozaj formunda bir yeni uzun etkili farmasötik kombinasyon ile ilgilidir. Mevcut bulusa göre farmasötik kombinasyon, ropivakain, klonidin, betametazon veya bunlarin farmasötik olarak uygun tuzlarini ve hidratlarini ihtiva etmektedir. More particularly, the invention provides a parenteral dosage method that can be administered before or after surgery. It concerns a new long-acting pharmaceutical combination in the form of Pharmaceutical according to the present invention The combination includes ropivacaine, clonidine, betamethasone or pharmaceutically acceptable salts thereof. and its hydrates.
Teknigin Bilinen Durumu Lokal anestezikler, sinir liflerinin sodyum kanallarini tersine çevrilerek bloke edilmesi ile, sinir uyarilarinin iletimini engelleyerek uygulandiklari bölgede agri hissini etkisiz hale getiren ilaçlardir. Lokal anestezikler, çözelti, krem, jel, lipozomal kapsül, tablet ve sprey formülasyonlari dahil olmak üzere farkli farmasötik dozaj formlarinda piyasada mevcuttur. Lokal anesteziklerle iliskili yaygin bir sorun ise, yari ömürlerinin hasta için daha uzun bir etki ve daha fazla konfor saglamak için yeterince uzun olmamasidir. Lokal anesteziklerin çogu görünür etkilerini yaklasik iki ila alti saat içinde kaybeder ki bu, özellikle ameliyat sonrasi kosullarda genellikle yeterli degildir. Geleneksel lokal anesteziklerin bir baska sorunu ise, diger ilaçlarla kombinasyonlarinin iyi tolere edilmemesi sebebiyle yan etkilere neden olmasidir. Ayrica, etkileri çogunlukla doza baglidir ve daha uzun sürelerde agri yönetimi için daha yüksek dozlar gerekmektedir. içeren bir listeden seçilen bir aktif maddeyi ihtiva eden modifiye edilmis salimli bir mikropartikülat sistemini açiklamaktadir. Mikropartiküllerin iyi tolere edilebilir ve ekonomik olarak kolaylikla elde edilebilir olduklari için avantajli olduklari söylenmektedir. partikülleri, hidrofobik salim kontrol edici ajan ve bir kaplama içeren bir modifiye edilmis salimli dozaj formu saglamaktadir. Ayrica, modifiye edilmis salimla formüle edilebilen anestezikler, analjezikler ve steroidler dahil olmak üzere alternatif aktif bilesenlerin uzun listeleri mevcuttur. Known Status of the Technique Local anesthetics act by reversibly blocking the sodium channels of nerve fibres. It neutralizes the feeling of pain in the area where it is applied by preventing the transmission of warnings. are drugs. Local anesthetics, solution, cream, gel, liposomal capsule, tablet and spray formulations It is commercially available in different pharmaceutical dosage forms including: With local anesthetics A common problem associated with this is that their half-life does not provide a longer effect and greater comfort for the patient. It is not long enough to provide Most local anesthetics have visible effects for about It disappears within two to six hours, which is usually sufficient, especially in postoperative conditions. It is not. Another problem with traditional local anesthetics is that their combination with other drugs It may cause side effects because it is not well tolerated. Additionally, effects mostly depend on the dose. and higher doses are required for pain management over longer periods of time. A modified-release preparation containing an active ingredient selected from a list containing Explains the microparticulate system. Microparticles are well tolerated and economical. It is said that they are advantageous because they are easily obtainable. A modified release agent containing particles, a hydrophobic release controlling agent and a coating. Provides dosage form. Additionally, anesthetics that can be formulated with modified release, Long lists of alternative active ingredients are available, including analgesics and steroids.
WO 11139595 A2, bir terapötik ajani spinal kolona uygulamak için bir spesifik Cihazi açiklamaktadir; burada terapötik ajan, analjezik ve anti-enflamatuar ajanlari içeren belirli bir listeden seçilmektedir. WO 11139595 A2 describes a specific Device for administering a therapeutic agent to the spinal column explains; wherein the therapeutic agent is a specific combination of analgesic and anti-inflammatory agents. is selected from the list.
WO 9851290 A2, lokal anestezikler, vazokonstriktörler, adrenerjik ilaçlar, vanilloidler, amfifilik çözücüler, lipofilik çözücüler, glukokortikoidler ve kontrollü veya uzun süreli salim formülasyonlarindan olusan gruptan seçilen bir maddeyi içeren, sinir blokajina neden olmak için lokal anestezik formülasyonlari açiklamaktadir. Önceki teknige ait söz konusu formülasyonlar ayrica, özellikle ameliyat sonrasi kosullarda hasta için istenen rahatligi saglamak için yetersizdir. Formülasyonlarda daha yüksek dozlar kullanilsa bile daha fazla tolere edilebilirken daha uzun bir etkiye sahip olabilen lokal anestezik olarak saglanan spesifik bir tedavi mevcut degildir. Uyumsuz ve tolere edilemez olabildikleri için ikiden fazla aktif bilesene sahip lokal anestezikleri formüle etmek zordur. Buna ek olarak, lokal anesteziklerin analjezik ajanlarla kombinasyonlari, hastanin yeteneklerini ve hareketini engelleyebilen motor nöronlarin bloke olmasina neden olabilir. Lokal anestezikler ayrica, ciddi doku hasarlari içeren cerrahi anestezide kullanim için uygun degildir. Bu nedenle, hastanin konforunu artirmak amaciyla gelismis lokal anestezikler saglamak için teknigin bilinen durumunda hala karsilanmamis bir ihtiyaç mevcuttur. Bu problemler, ekli istemlerde tanimlandigi gibi ropivakain, klonidin, betametazon veya bunlarin farmasötik olarak uygun tuzlari ve hidratlarini ihtiva eden bir farmasötik kombinasyon ile çözülmektedir. WO 9851290 A2, local anesthetics, vasoconstrictors, adrenergic drugs, vanilloids, amphiphilic solvents, lipophilic solvents, glucocorticoids and controlled or prolonged release containing a substance selected from the group consisting of formulations to cause nerve blockade Explains local anesthetic formulations. Said prior art formulations are also suitable for patients, especially in post-operative conditions. It is insufficient to provide the desired comfort. Even if higher doses are used in the formulations as a local anesthetic which may have a longer effect while being more tolerable There is no specific treatment provided. Because they can be incompatible and intolerable, more than two It is difficult to formulate local anesthetics with too many active ingredients. In addition, local Combinations of anesthetics with analgesic agents affect the patient's abilities and movement. It may cause blockage of motor neurons that can inhibit Local anesthetics can also cause serious It is not suitable for use in surgical anesthesia involving tissue damage. Therefore, the patient The technique is known to provide advanced local anesthetics to increase comfort. There is still an unmet need. These problems are addressed in the appended claims. ropivacaine, clonidine, betamethasone or their pharmaceutically acceptable It is dissolved by a pharmaceutical combination containing its salts and hydrates.
Mevcut bulusa ait farmasötik kombinasyon ile, hastalarin hastanede gece kalmasini gerektirmediginden, belirli operasyonlarin günlük cerrahisi uygulanabilir hale gelmektedir. Genel anestezinin kullanimi ortadan kalktigi için komplikasyonlarini azaltmak da mümkündür. With the pharmaceutical combination of the present invention, patients are prevented from staying overnight in the hospital. Since it does not require surgery, day surgery for certain operations becomes feasible. General It is also possible to reduce complications since the use of anesthesia is eliminated.
Hastalarin bagimliliga neden olan agir analjezik ve opioid alimina ihtiyaci kalmamaktadir. Ayrica, mevcut bulusa ait yeni kombinasyonlar kararlidir ve kombinasyonda kullanilan aktif bilesenlerin kimyasal yapisi ve spesifik dozlari nedeniyle düsük toksisite sergilemektedir. Patients do not need to take heavy analgesics and opioids that cause addiction. Moreover, The new combinations of the present invention are stable and the active ingredients used in the combination It exhibits low toxicity due to its chemical structure and specific doses.
Bulusun Kisa Açiklamasi Mevcut bulus, asagidaki bilesenleri veya bunlarin farmasötik olarak uygun tuzlarini ve hidratlarini ihtiva eden bir parenteral dozaj formundaki bir farmasötik kombinasyon ile ilgilidir: Bilesen Miktar Ropivakain 10 mg ila 200 mg Klonidin 2,5 pg ila 100 pg Betametazon 1 mg ila 10 mg Yukarida görüldügü gibi, mevcut bulusa göre lokal anestezik ajan ropivakain veya bunun farmasötik tuzlari ve hidratlaridir. Daha tercihen, lokal anestezik ajan, ropivakainin hidroklorür tuzudur ve daha da tercihen, ropivakain hidroklorür monohidrattir. Ropivakainin S-enantiyomeri, aktif bilesenin tercih edilen formudur. Ropivakain dozu, tercihen yaklasik 25 mg'dir. Brief Description of the Invention The present invention includes the following compounds or their pharmaceutically acceptable salts and It relates to a pharmaceutical combination in a parenteral dosage form containing hydrates of: Component Quantity Ropivacaine 10 mg to 200 mg Clonidine 2.5 pg to 100 pg Betamethasone 1 mg to 10 mg As seen above, according to the present invention the local anesthetic agent is ropivacaine or its pharmaceutical salts and hydrates. More preferably, the local anesthetic agent is ropivacaine hydrochloride. salt and, more preferably, ropivacaine hydrochloride monohydrate. S-enantiomer of ropivacaine, is the preferred form of the active ingredient. The dose of ropivacaine is preferably approximately 25 mg.
Mevcut bulusa ait yeni kombinasyonlarda kullanildigi sekliyle klonidin, tercihen klonidin hidroklorürdür. Klonidin dozu tercihen yaklasik 75 ug'dir. Clonidine, preferably clonidine, as used in the novel combinations of the present invention. is hydrochloride. The clonidine dose is preferably approximately 75 µg.
Mevcut bulusa göre kortikosteroid ajanin, yani betametazon veya bunun farmasötik olarak uygun tuzlarinin, deksametazon ve beklometazon gibi diger kortikosteroidlere kiyasla daha avantajli oldugu bulunmustur. Betametazon dozu, tercihen yaklasik 2 mg'dir. According to the present invention, the corticosteroid agent, namely betamethasone or its pharmaceutically acceptable salts have advantages over other corticosteroids such as dexamethasone and beclomethasone. It has been found that . The dose of betamethasone is preferably approximately 2 mg.
Bu nedenle, tercih edilen bir yapilanmada, mevcut bulusa ait kombinasyon asagidaki bilesenleri ihtiva etmektedir: Bilesen Konsantrasyon Ropivakain 1 ila 20 mg/ml Klonidin 5 ila 100 ug/ml Betametazon 0,1 ila 10 mg/ml Daha tercih edilen bir yapilanmada, mevcut bulusa ait kombinasyon asagidaki bilesenleri ihtiva etmektedir: Bilesen Miktar Ropivakain hidroklorür monohidrat yaklasik 25 mg ropivakain serbest baza esdeger Klonidin hidroklorür yaklasik 75 ug klonidin serbest baza esdeger Betametazon yaklasik 2 mg Salin yaklasik 10 ml Mevcut bulusa göre farmasötik kombinasyon, tercihen bir farmasötik olarak uygun tasiyici içinde bir tek doz halinde formüle edilmis olarak bir kompozisyon formundadir. Tercihen, söz konusu farmasötik olarak uygun tasiyici, sodyum ve enjeksiyonluk su içeren salin ihtiva eder. Söz konusu farmasötik kombinasyon, lipozom, nanokapsül ve mikrokapsülden olusan bir gruptan seçilen bir tasiyici ihtiva eden bir uzatilmis salimli dozaj formu seklinde saglanabilir. Therefore, in a preferred embodiment, the combination of the present invention includes the following components: contains: Component Concentration Ropivacaine 1 to 20 mg/ml Clonidine 5 to 100 µg/ml Betamethasone 0.1 to 10 mg/ml In a more preferred embodiment, the combination of the present invention includes the following components: is doing: Component Quantity Ropivacaine hydrochloride monohydrate approximately 25 mg ropivacaine free base equivalent Clonidine hydrochloride approximately 75 µg clonidine free base equivalent Betamethasone approximately 2 mg Saline approximately 10 ml The pharmaceutical combination according to the present invention is preferably in a pharmaceutically acceptable carrier. It is in the form of a composition formulated as a single dose. Preferably, it is The pharmaceutically acceptable carrier contains saline with sodium and water for injection. Aforementioned The pharmaceutical combination is a drug selected from the group consisting of liposomes, nanocapsules and microcapsules. may be provided in the form of an extended-release dosage form containing a carrier.
Mevcut bulusa göre farmasötik kombinasyon, anestezi ve agri kontrolünde kullanilmak üzere saglanmaktadir. Burada belirtildigi gibi söz konusu anestezi, bölgesel anestezi, spinal anestezi veya epidural anestezi ihtiva edebilir. Söz konusu farmasötik kombinasyon intradermal, subkütan, intramüsküler, intraosseöz, intraperitonel, intravenöz veya intravertebral yolla enjeksiyon veya infüzyon ile uygulanabilmektedir. Bahsedilen farmasötik kombinasyon, her tip ameliyat için kullanilabilen uzun süreli lokal anestezi saglamaktadir. Ancak özellikle ameliyat (örnegin; ortopedik ameliyat) sonrasi agri kontrolünde faydalidir. The pharmaceutical combination according to the present invention is for use in anesthesia and pain control. is provided. As stated here, the anesthesia in question includes regional anesthesia, spinal anesthesia. or may involve epidural anesthesia. The pharmaceutical combination in question is intradermal, subcutaneous, intramuscular, intraosseous, intraperitoneal, intravenous or intravertebral It can be administered by injection or infusion. Said pharmaceutical combination, each type It provides long-term local anesthesia that can be used for surgery. However, especially surgery It is useful in pain control after (for example, orthopedic surgery).
Bulusun Ayrintili Açiklamasi Mevcut bulusa ait lokal anestezik kombinasyon, iyi tolere edilebildigi ve sasirtici bir sekilde motor sinirleri bloke etmeden agri kontrolünde daha uzun bir etkiye sahip oldugu, ve bu nedenle hastanin hareket ve yeteneklerinin engellenmesine neden olmadigi bulunmus olan en az üç farkli aktif bilesen türünü, yani ropivakain, klonidin, betametazon veya bunlarin farmasötik olarak uygun tuzlari ve hidratlarini avantajli bir sekilde içermektedir. Mevcut bulusa göre yeni kombinasyonun özellikle ortopedi hastalarinin agrisinin ve daha da özel olarak ortopedik cerrahinin ameliyat sonrasi agrisinin kontrol edilmesinde avantajli oldugu bulunmustur. Detailed Description of the Invention The local anesthetic combination of the present invention is well tolerated and surprisingly effective in reducing motor activity. It has a longer effect in pain control without blocking the nerves, and therefore At least three different methods have been found to not hinder the patient's movements and abilities. the type of active ingredient, i.e. ropivacaine, clonidine, betamethasone or their pharmaceutical form It advantageously contains appropriate salts and hydrates thereof. New according to the present invention The combination is particularly effective in reducing pain in orthopedic patients and more specifically in orthopedic Surgery has been found to be advantageous in controlling postoperative pain.
Mevcut bulusta kullanildigi sekliyle ropivakain, geleneksel olarak bir amid grubu ile bilinen Ropivakain anestezik bir bilesiktir. Ropivacaine, as used in the present invention, is a compound conventionally known as an amide group. Ropivacaine It is an anesthetic compound.
Ropivakain tercihen hidroklorür tuzu olarak ve bunun S-enantiyomeri olarak akut agri yönetimi ve cerrahi anestezi için kullanilmaktadir. Intravenöz olarak uygulanan ropivakain, 14 dakikalik baslangiç fazinin ortalama yari ömrüne sahiptir, ardindan yaklasik 4,2 saatlik bir ortalama absorpsiyon tuz ile daha yavas bir faz izlemektedir [Kuthiala et al., Ropivacaine: A review ofits ropivakain görünür etkisini yaklasik 4 saat içinde kaybeder ve daha uzun bir etki için ek dozlar gerekmektedir. Ropivacaine, preferably as its hydrochloride salt and its S-enantiomer, for the management of acute pain and used for surgical anesthesia. Ropivacaine administered intravenously for 14 minutes It has an average half-life of the initial phase followed by an average of approximately 4.2 hours. absorption follows a slower phase with salt [Kuthiala et al., Ropivacaine: A review of Ropivacaine loses its apparent effect in about 4 hours and additional doses may be required for a longer effect. is required.
Klonidin, genellikle kan basincini düsürmek ve belirli agri türlerini hafifletmek için kullanilan bir ajandir. Klonidin asagidaki genel formüle sahiptir: Klonidin Mevcut bulus baglaminda, klonidin tercihen bunun hidroklorür tuzu olarak kullanilir. Klonidin, az reseptörlerini uyararak kan akisini sinirlar ve anestezinin etki süresini uzatir. Clonidine is a drug often used to lower blood pressure and relieve certain types of pain. agent. Clonidine has the following general formula: clonidine In the context of the present invention, clonidine is preferably used as its hydrochloride salt. Clonidine, little By stimulating the receptors, it limits the blood flow and prolongs the duration of effect of anesthesia.
Betametazon, teknikte asagidaki genel formül ile bilinen bir kortikosteroid ajandir: Betametazon Mevcut bulusa ait yeni kombinasyonun, motor sinirleri bloke etmeden ancak sadece duyuyu azaltarak agri kontrolünde daha uzun bir etki sagladigi için özellikle hastanin konforunu artirdigi bulunmustur. Betamethasone is a corticosteroid agent known in the art with the following general formula: Betamethasone The new combination of the present invention allows only sensory stimulation without blocking motor nerves. It especially increases the comfort of the patient as it provides a longer effect in pain control by reducing has been found.
Bu nedenle, mevcut bulus bir yönüyle, yukaridaki aktif bilesenleri ihtiva eden bir parenteral dozaj formunda bir farmasötik kombinasyon saglamaktadir. Söz konusu kombinasyon, bir denekte agrinin yönetimi için bir arada veya eszamanli olarak uygulanabilmektedir. Daha tercihen, bahsedilen kombinasyon, söz konusu aktifbilesenlerin farmasötik olarak uygun bir tasiyici içinde karistirilmasiyla hazirlanan bir parenteral dozaj formunda bir "farmasötik kompozisyon" olarak saglanmaktadir. Mevcut bulusa ait parenteral kombinasyon, intradermal, subkütan, intramüsküler, intraosseöz, intraperitoneal, intravenöz veya intravertebral yolla uygulama için uygun bir spesifik dozaj formunda saglanabilmektedir. Cerrahide ameliyat sonrasi agri kontrolünde, daha tercihen ortopedik cerrahide ameliyat sonrasi agri kontrolünde özellikle faydalidir. Therefore, in one aspect, the present invention provides a parenteral dosage form containing the above active ingredients. It provides a pharmaceutical combination in the form of The combination in question was They can be applied together or simultaneously for the management of pain. More preferably, said combination comprising said active ingredients in a pharmaceutically acceptable carrier. As a "pharmaceutical composition" in a parenteral dosage form prepared by mixing is provided. The parenteral combination of the present invention includes intradermal, subcutaneous, For administration by intramuscular, intraosseous, intraperitoneal, intravenous or intravertebral route may be provided in a suitable specific dosage form. Postoperative pain in surgery control, more preferably in orthopedic surgery, especially in postoperative pain control It is useful.
Mevcut bulus diger bir yönüyle, söz konusu kombinasyonun bir hastaya cerrahi operasyon öncesinde, sirasinda veya sonrasinda uygulanmasini ihtiva eden cerrahi anestezide yukaridaki kombinasyonun yeni kullanimini saglamaktadir. Söz konusu uygulama, örnegin intravenöz infüzyon veya subkütan yoldan ve daha özel olarak infiltrasyon anestezisî veya epidural uygulama yoluyla olabilir. Mevcut bulusa göre olan kombinasyonun, özellikle diger cerrahi operasyonlara kiyasla genellikle daha uzun süre agrili olan osteotomi [kemik kesisi] sonrasi agri yönetimi için basarili oldugu bulunmustur. In another aspect, the present invention provides that said combination does not require surgical intervention on a patient. In surgical anesthesia, which includes the application before, during or after the above mentioned It provides a new use of the combination. The application in question is, for example, intravenous by infusion or subcutaneous administration, and more specifically by infiltration anesthesia or epidural administration It can be via. The combination according to the present invention is particularly useful in other surgical operations. for pain management after osteotomy [bone cutting], which is often painful for a longer period of time compared to It has been found to be successful.
Mevcut bulus daha ileri bir yönüyle, söz konusu kombinasyonun, yukarida bahsedildigi gibi, örnegin sürekli infüzyon veya aralikli enjeksiyonlar parenteral yolla bir hastaya uygulanmasini ihtiva eden akut agri yönetiminde yukaridaki kombinasyonun yeni kullanimini saglamaktadir. In a further aspect, the present invention provides that said combination, as mentioned above, For example, continuous infusion or intermittent injections require parenteral administration to a patient. It provides a new use of the above combination in the management of acute pain.
Tercih edilen yapilanmalarda, enjekte edilen çözeltinin toplam hacmindeki ropivakain konsantrasyonu, 1 ila 20 mg/ml araliginda, daha tercihen 2,5 ila 5 mg/ml araliginda ve daha da tercihen yaklasik 2,5 mg/ml'dir. Her doz, istenen etkiyi elde etmek için yeterli olan 10 mg ila 200 mg ve daha tercihen yaklasik 25 mg lokal anestezik içerebilir. In preferred embodiments, ropivacaine in the total volume of solution injected concentration in the range of 1 to 20 mg/ml, more preferably in the range of 2.5 to 5 mg/ml and further preferably about 2.5 mg/ml. Each dose contains 10 mg to 200 mg, which is enough to achieve the desired effect. It may contain mg, and more preferably about 25 mg, of local anesthetic.
Mevcut bulusta kullanildigi sekliyle klonidin, 5 ila 100 tig/ml araliginda, daha tercihen 5 ila 10 tig/ml araliginda bir konsantrasyon ile saglanabilmektedir. Her doz 2,5 ug ila 100 tig ve daha tercihen yaklasik 75 ug klonidin içerebilir. Bu doz degerleri genellikle piyasada bulunan geleneksel tek doz degerlerinden daha düsüktür. Bu nedenle mevcut bulus, istenen terapötik etkinin daha düsük doz degerleriyle elde edilmesi ve bunun da kombinasyon tedavisinin yan etkilerini azaltmasi ve tolere edilebilirligini artirmasi açisindan avantajlidir. Clonidine as used in the present invention is available in the range of 5 to 100 μg/ml, more preferably 5 to 10 μg/ml. It can be achieved with a concentration in the range of tig/ml. Each dose 2.5 ug to 100 tig and more preferably it may contain about 75 µg clonidine. These dosage values are generally available on the market. It is lower than traditional single dose values. Therefore, the present invention provides the desired therapeutic The effect is achieved with lower dosage values and this results in the side effects of combination therapy. It is advantageous in terms of reducing its effects and increasing its tolerability.
Mevcut bulusa göre betametazon, 0,1 ila 10 mg/ml, daha tercihen 0,2 ila 1 mg/ml araliginda bir konsantrasyon ile sunulabilmektedir. Her doz 1 mg ila 10 mg ve daha tercihen 1 mg ila 4 mg betametazon içerebilir. En iyi sonuçlar yaklasik 2 mg'lik bir dozla elde edilmektedir. According to the present invention, betamethasone is administered at a dose in the range of 0.1 to 10 mg/ml, more preferably 0.2 to 1 mg/ml. can be presented with concentration. Each dose 1 mg to 10 mg and more preferably 1 mg to 4 mg May contain betamethasone. Best results are achieved with a dose of approximately 2 mg.
Mevcut tarifname baglaminda, yukarida bahsedilen dozlar ve miktarlar, serbest baz formundaki aktif bilesenlere isaret etmektedir. Söz konusu aktif bilesenlerin farmasötik olarak uygun tuzlari ve hidratlari, yukaridaki miktarlarda ve serbest baz formuna esdeger dozlarda aktif moleküller Tercihen, söz konusu parenteral dozaj formundaki farmasötik kombinasyon asagidaki bilesenleri ihtiva eder: - ropivakain hidroklorür monohidrat, - klonidin hidroklorür, - betametazon. In the context of the present specification, the doses and amounts mentioned above are in the form of free base. refers to active components. Pharmaceutically acceptable salts of said active ingredients and their hydrates, in the above amounts and in doses equivalent to the free base form of the active molecules Preferably, the pharmaceutical combination in said parenteral dosage form includes the following ingredients: contains: - ropivacaine hydrochloride monohydrate, - clonidine hydrochloride, - betamethasone.
Mevcut bulusa göre farmasötik kombinasyon, agri kontrolü için anestezide daha uzun ve saglam bir etki saglasa da, söz konusu kombinasyon, lipozom, nanokapsül ve mikrokapsülden olusan gruptan seçilen bir tasiyiciyi içeren bir uzatilmis salimli dozaj formu seklinde saglanabilir; özellikle agir yaralanmalarda arzu edilebilir. The pharmaceutical combination according to the present invention provides a longer and more durable effect in anesthesia for pain control. Although it provides an effect, the combination in question consists of liposome, nanocapsule and microcapsule. may be provided as an extended-release dosage form containing a carrier selected from the group consisting of; It may be especially desirable in cases of severe injuries.
Mevcut bulusun daha ileri yönleri ve yapilanmalari, ekli istemlerden anlasilacaktir. Further aspects and embodiments of the present invention will be apparent from the appended claims.
Ropivakain hidroklorür monohidratin anestezik preparatlari, aktif bilesenlerin salin içerisinde karistirilmasiyla asagidaki kompozisyon ile hazirlanmistir. Söz konusu kompozisyonlar, ortopedik cerrahi ile tedavi edilen hastalara uygulanmistir. Anesthetic preparations of ropivacaine hydrochloride monohydrate contain the active ingredients in saline solution. It was prepared by mixing with the following composition. The compositions in question are It was applied to patients treated with orthopedic surgery.
Kompozisyon Bilesen Miktar Ropivakain hidroklorür monohidrat 25 mg (2,5 mg/ml] Klonidin hidroklorür 75 ug (7,5 tig/ml] Betametazon 2 mg (0,2 mg/ml] Salin 10 m1 Tüm kompozisyonlar, cerrahi operasyondan önce bolus infüzyon yoluyla uygulanmistir ve hastalara, ameliyattan sonraki 24 saatlik bir süre boyunca her saat basi, ameliyat sonrasi agriyi rahatsiz edici düzeyde hissedip hissetmedikleri sorulmustur. Anesteziye ragmen hastalarin hiçbirinin motor becerilerini kaybetmedigi ve vücut kisimlarini hareket ettirebildigi kaydedilmistir. Söz konusu kompozisyonu alan hastalar, 24 saatlik bir süre içinde ekstra ilaç almadan ameliyat sonrasi agriya dayanabilmislerdir ve bu süre boyunca hiç agri hissetmemisler veya orta dereceli agri hissetmislerdir. Composition Component Quantity Ropivacaine hydrochloride monohydrate 25 mg (2.5 mg/ml] Clonidine hydrochloride 75 ug (7.5 tig/ml] Betamethasone 2 mg (0.2 mg/ml] Saline 10 m1 All compositions were administered via bolus infusion prior to surgery and patients were asked to monitor postoperative pain every hour for a 24-hour period after surgery. They were asked whether they felt it was disturbing or not. Despite anesthesia, patients None of them lost their motor skills and could move their body parts. has been recorded. Patients taking the composition in question should not take extra medication within a 24-hour period. They were able to withstand the postoperative pain without any pain and did not feel any pain during this period. or they felt moderate pain.
Söz konusu kompozisyon sasirtici bir sekilde, ameliyat sonrasi agri yönetiminde motor sinirlerin isleyisinde herhangi bir kayip, yan etkiler ve tolere edilebilîrlikte sorunlar olmaksizin daha uzun bir etki saglamistir. Hastalar aralikli dozlara ihtiyaç duymadan kendilerini daha rahat hissetmislerdir. Surprisingly, the composition in question was effective in improving motor nerves in post-operative pain management. longer without any loss of functioning, side effects or problems in tolerability. has had an effect. Patients feel more comfortable without the need for intermittent doses. They felt it.
Hastalarin anestezisi için kullanilan üçlü kombinasyonun çok uzun süre belirgin agri, motor fonksiyonlarda kayip ve parezi (kismi felç) olmaksizin etki sagladigi ilginç bir sekilde ortaya koyulmaktadir. Bulus sahipleri, bir teoriye bagli kalmak istemeksizin, betametazon için merkezi sinir sisteminin geçirgenliginin, deksametazon gibi diger kortikosteroidlerden daha düsük oldugunu ve bu nedenle yukarida bahsedilen istenen etkilerin, spesifik kortikosteroid ve mevcut bulusa göre aktifbilesenlerin dozlari ile iyilestirildigini düsünmektedir. The triple combination used for anesthesia of patients causes significant pain and motor problems for a very long time. Interestingly, it has been revealed that it provides effect without loss of functions and paresis (partial paralysis). is placed. The inventors, without wishing to adhere to a theory, proposed the central theory for betamethasone. lower permeability of the nervous system than other corticosteroids such as dexamethasone and therefore the desired effects mentioned above are due to the specific corticosteroid and It is thought to be improved by doses of the active ingredients according to the invention.
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR2021009613T true TR2021009613T (en) | 2022-03-21 |
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