SK54599A3 - Composition for the treatment of asthma, containing loratadine and a decongestant - Google Patents
Composition for the treatment of asthma, containing loratadine and a decongestant Download PDFInfo
- Publication number
- SK54599A3 SK54599A3 SK545-99A SK54599A SK54599A3 SK 54599 A3 SK54599 A3 SK 54599A3 SK 54599 A SK54599 A SK 54599A SK 54599 A3 SK54599 A3 SK 54599A3
- Authority
- SK
- Slovakia
- Prior art keywords
- loratadine
- pseudoephedrine
- asthma
- administered
- use according
- Prior art date
Links
- 208000006673 asthma Diseases 0.000 title claims abstract description 39
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 229960003088 loratadine Drugs 0.000 title claims abstract description 32
- 239000000850 decongestant Substances 0.000 title claims abstract description 20
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 239000000203 mixture Substances 0.000 title claims description 16
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims abstract description 26
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims abstract description 23
- 229960003908 pseudoephedrine Drugs 0.000 claims abstract description 22
- 206010039083 rhinitis Diseases 0.000 claims abstract description 11
- 230000009325 pulmonary function Effects 0.000 claims abstract description 8
- 238000009472 formulation Methods 0.000 claims description 9
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims description 8
- 229940124581 decongestants Drugs 0.000 claims description 8
- 229960002179 ephedrine Drugs 0.000 claims description 4
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 claims description 3
- -1 phenylephedrine Chemical compound 0.000 claims description 3
- 229960000395 phenylpropanolamine Drugs 0.000 claims description 3
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims 2
- 238000000576 coating method Methods 0.000 claims 2
- 239000008247 solid mixture Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- 239000003814 drug Substances 0.000 description 24
- 229940079593 drug Drugs 0.000 description 21
- 208000024891 symptom Diseases 0.000 description 15
- 239000000739 antihistaminic agent Substances 0.000 description 14
- 230000006872 improvement Effects 0.000 description 11
- 206010039085 Rhinitis allergic Diseases 0.000 description 8
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 8
- 201000010105 allergic rhinitis Diseases 0.000 description 8
- 229940125715 antihistaminic agent Drugs 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 7
- 229960001803 cetirizine Drugs 0.000 description 7
- 239000000902 placebo Substances 0.000 description 6
- 229940068196 placebo Drugs 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 208000026935 allergic disease Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 5
- 229960000351 terfenadine Drugs 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- HUCJFAOMUPXHDK-UHFFFAOYSA-N Xylometazoline Chemical compound CC1=CC(C(C)(C)C)=CC(C)=C1CC1=NCCN1 HUCJFAOMUPXHDK-UHFFFAOYSA-N 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000000932 sedative agent Substances 0.000 description 4
- 230000001624 sedative effect Effects 0.000 description 4
- CAVQBDOACNULDN-NRCOEFLKSA-N (1s,2s)-2-(methylamino)-1-phenylpropan-1-ol;sulfuric acid Chemical compound OS(O)(=O)=O.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 CAVQBDOACNULDN-NRCOEFLKSA-N 0.000 description 3
- 206010011224 Cough Diseases 0.000 description 3
- 208000000059 Dyspnea Diseases 0.000 description 3
- 206010013975 Dyspnoeas Diseases 0.000 description 3
- 208000037656 Respiratory Sounds Diseases 0.000 description 3
- 206010047924 Wheezing Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 229940124630 bronchodilator Drugs 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229960004159 pseudoephedrine sulfate Drugs 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229960002052 salbutamol Drugs 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010070774 Respiratory tract oedema Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940124623 antihistamine drug Drugs 0.000 description 2
- 229940127225 asthma medication Drugs 0.000 description 2
- 239000000168 bronchodilator agent Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960005139 epinephrine Drugs 0.000 description 2
- 239000000938 histamine H1 antagonist Substances 0.000 description 2
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 208000013220 shortness of breath Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- BYJAVTDNIXVSPW-UHFFFAOYSA-N tetryzoline Chemical compound N1CCN=C1C1C2=CC=CC=C2CCC1 BYJAVTDNIXVSPW-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 229960000833 xylometazoline Drugs 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- PDNHLCRMUIGNBV-UHFFFAOYSA-N 1-pyridin-2-ylethanamine Chemical compound CC(N)C1=CC=CC=N1 PDNHLCRMUIGNBV-UHFFFAOYSA-N 0.000 description 1
- 208000000884 Airway Obstruction Diseases 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone 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)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 229940124056 Histamine H1 receptor antagonist Drugs 0.000 description 1
- 229940122236 Histamine receptor antagonist Drugs 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- VQDBNKDJNJQRDG-UHFFFAOYSA-N Pirbuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 VQDBNKDJNJQRDG-UHFFFAOYSA-N 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 230000008369 airway response Effects 0.000 description 1
- 208000028004 allergic respiratory disease Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 231100000457 cardiotoxic Toxicity 0.000 description 1
- 230000001451 cardiotoxic effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 208000029771 childhood onset asthma Diseases 0.000 description 1
- 229940088529 claritin Drugs 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 208000027744 congestion Diseases 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- KBYGOCNIUHCOLP-MNIONDOCSA-N ethyl 4-(8-chloro-5,6-dihydrobenzo[1,2]cyclohepta[2,4-b]pyridin-11-ylidene)piperidine-1-carboxylate;(1s,2s)-2-(methylamino)-1-phenylpropan-1-ol;sulfuric acid Chemical compound OS(O)(=O)=O.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 KBYGOCNIUHCOLP-MNIONDOCSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- YAHRDLICUYEDAU-UHFFFAOYSA-N methylhexaneamine Chemical compound CCC(C)CC(C)N YAHRDLICUYEDAU-UHFFFAOYSA-N 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229960005016 naphazoline Drugs 0.000 description 1
- 229960002259 nedocromil sodium Drugs 0.000 description 1
- 229960002657 orciprenaline Drugs 0.000 description 1
- 229960001528 oxymetazoline Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 229960005414 pirbuterol Drugs 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229960003447 pseudoephedrine hydrochloride Drugs 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000004335 respiratory allergy Diseases 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 229960000337 tetryzoline Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Vynález sa týka spôsobu zmierňovania symptómov alergických ochorení a konkrétnejšie zmierňovanie symptómov bronchiálnej astmy.The invention relates to a method for alleviating the symptoms of allergic diseases and more particularly to alleviating the symptoms of bronchial asthma.
Doterajší stav technikyBACKGROUND OF THE INVENTION
Astma sa považuje za velmi vážnu chronickú alergickú poruchu a typicky je charakterizovaná neprimeranými reakciami dýchacích ciest s príznakmi kašľa, chripenia a stratou dychu. V detstve je jednou z najbežnejších chorôb a postihuje asi desať percent detí. Astma je ekonomicky veľmi významná, lebo spôsobuje závažné straty času v zamestnaní a v školách, je jednou z najčastejších príčin návštev u lekára a je zodpovedná za mnohé prijatia do zariadení akútnej starostlivosti a nemocníc. Astma je tiež zodpovedná za významnú úmrtnosť, zvlášť keď sa správne nelieči.Asthma is considered a very serious chronic allergic disorder and is typically characterized by inadequate respiratory reactions with cough, wheezing, and breathlessness symptoms. It is one of the most common diseases in childhood and affects about ten percent of children. Asthma is very important economically because it causes serious time loss in employment and in schools, is one of the most common causes of doctor visits and is responsible for many admissions to acute care facilities and hospitals. Asthma is also responsible for significant mortality, especially when not properly treated.
Všeobecné sa uznáva, že astma je charakterizovaná chronickým zápalom dýchacích ciest, rôznym stupňom obštrukcie dýchacích ciest s častou návratnosťou a zvýšením reakcií v dýchacích cestách na rôzne podnety. Pri silnom akútnom podráždení, ktoré chorí bežne označujú ako „astmatický záchvat, sa často pozorujú svalové kŕče, edém dýchacích ciest, abnormálna tvorba hlienu a zápalový bunkový filtrát.It is generally recognized that asthma is characterized by chronic airway inflammation, varying degrees of airway obstruction, with frequent recurrence, and increased airway responses to various stimuli. Severe acute irritation, commonly referred to as an "asthma attack" by the patient, is commonly observed for muscle cramps, airway edema, mucus abnormal formation, and an inflammatory cell filtrate.
Edém dýchacích ciest a bronchospazmus možno bežne úspešne liečiť bronchodilatátormi, ako sú epinefrin a P2-agonista albuterol (nazývaný tiež „salbutamol), metaproterenol, pirbuterol, terbutalin a salmeterol. Zúženie dýchacích ciest možno bežne zablokovať podávaním systémových kortikosteroidov, ako je prednizon alebo inhaláciou protizápalových liekov, ako sú beclometazon dipropionát, flunizolid, triamcinolon acetonid, cromolyn sodný a nedocromil sodný. p2-agonisty sa používajú ako denná udržiavacia dávka a ako „záchranné liečenie, pričom sa podávajú podlá potreby, keď sa objavia príznaky silného podráždenia. Systémové kortikosteroidy sa podávajú terapeuticky, bežne vo velkých dávkach pri liečení astmatického stavu, pričom kortikosteroidy sú profylaktické a sú podávané pri vážnejších prípadoch v pravidelne rozložených dávkach bez ohľadu na skutočné príznaky. Takéto liečenie vedie k zmierneniu kašľa, chripenia a pocitu straty dychu, plus k redukcii zužovania dýchacích ciest, ktoré môže byť ľahko kvantifikované meraním zlepšenia hodnôt pacientovho núteného výdychového objemu (FEV) alebo najvyššej rýchlosti výdychového prúdenia (PEF); stanovenie a význam týchto parametrov sú popísané sa stranách 584599 v R. Berkow (editor), The Merck Manula of Diagnosis and Therapy, pätnáste vydanie, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey, 1987, zvlášť na stranách 558-9. U niektorých pacientov je na kontrolu ochorenia požadovaná ďalšia orálna, injekčná alebo inhalačná liečba, pričom cieľom liečenia je eliminácia silného akútneho podráždenia.Airway edema and bronchospasm can normally be successfully treated with bronchodilators such as epinephrine and the β-agonist albuterol (also called "salbutamol"), metaproterenol, pirbuterol, terbutaline and salmeterol. Airway constriction can be routinely blocked by the administration of systemic corticosteroids such as prednisone or by inhalation of anti-inflammatory drugs such as beclomethasone dipropionate, flunizolide, triamcinolone acetonide, cromolyn sodium and nedocromil sodium. β 2 -agonists are used as a daily maintenance dose and as a "salvage treatment", administered as needed when symptoms of severe irritation occur. Systemic corticosteroids are administered therapeutically, usually in large doses for the treatment of asthma, with corticosteroids being prophylactic and administered in more severe cases at regularly spaced doses, regardless of the actual symptoms. Such treatment results in alleviation of cough, wheezing and feeling of loss of breath, plus a reduction in airway constriction, which can be easily quantified by measuring the improvement in patient forced expiratory volume (FEV) or peak expiratory flow rate (PEF); the determination and significance of these parameters are described in pages 584599 of R. Berkow (editor), The Merck Manual of Diagnosis and Therapy, Fifteenth Edition, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey, 1987, especially pages 558-9. In some patients, additional oral, injectable, or inhalation treatments are required to control the disease, with the aim of eliminating severe acute irritation.
Štúdia ukázali, že okolo 11 percent pacientov s príznakmi nosnej alergie trpia tiež astmou a že taký vysoký počet, ako je 80 percent osôb trpiacich bronchiálnou astmou môže mať tiež alergickú rinitídu. Ako patogénny mediátor bol u ochorení ako horných, tak dolných dýchacích ciest implikovaný histidín a boli uskutočnené štúdie na stanovenie účinku antagonistov histamínového Hi receptora, „antihistamínov na astmatické príznaky. Pri starších liekoch, často identifikovaných ako „sedatívne antihistamíny, boli účinky pozorované ako škodlivé pre astmatických pacientov a je preto konvenčným názorom, že antihistamínové lieky sú pre astmatikov kontraindikované. Typický je postoj uvádzaný J. E. Donnellym et al., Inadequate Paretal Understanding of Asthma Medications, Annals of Allergy, zv. 62, str. 337-341 (1989), kde sa na stranách 338-9 tvrdí:Studies have shown that about 11 percent of patients with nasal allergy symptoms also suffer from asthma and that as many as 80 percent of people with bronchial asthma may also have allergic rhinitis. Histidine has been implicated as a pathogenic mediator in diseases of both the upper and lower airways and studies have been conducted to determine the effect of histamine H 1 receptor antagonists, "antihistamines," on asthma symptoms. In older drugs, often identified as "sedative antihistamines, the effects have been observed to be harmful to asthmatic patients and it is therefore conventional that antihistamine drugs are contraindicated for asthmatics. Typically, the attitude presented by J. E. Donnelly et al., Inadequate Paretal Understanding of Asthma Medications, Annals of Allergy, Vol. 62, p. 337-341 (1989) where pages 338-9 claim:
Možno pozorovať, že podstatné percento detí, ktoré dostávajú antibiotiká, antihistamíny a dekongestanty na svoju astmu... Tieto tri skupiny liekov nemajú miesto v liečbe detskej astmy.It can be seen that a substantial percentage of children receiving antibiotics, antihistamines and decongestants for their asthma ... These three groups of drugs have no place in the treatment of childhood asthma.
Nástup antihistamínov so zníženým sedatívnym účinkom (ako je cetirizín) a nesedatívnych antihistamínov (ako sú terfenadin a loratadin) však obnovil záujem o liečenie astmy antihistamínmi. P. V. Williams et al. v kapitole nazvanej Asthma in Children v R. E. Rakel (editor), Conn's Current Therapy 1995, W. B. Sauňders Co., Philadelphia, Pennsylvania, 1995, str. 682-691, tvrdí na strane 686, že :However, the onset of reduced sedative antihistamines (such as cetirizine) and non-sedating antihistamines (such as terfenadine and loratadine) has renewed interest in the treatment of asthma with antihistamines. Williams, P.V. et al. in the chapter entitled Asthma in Children in R.E. Rakel (editor), Conn's Current Therapy 1995, W. B. Sauders Co., Philadelphia, Pennsylvania, 1995, p. 682-691, claims on page 686 that:
Antihistamíny sú slabé bronchodilátatory a novšie činidlá, z ktorých mnohé nie sú v Spojených štátoch dostupné, majú určité protizápalové účinky. Nie sú také účinné, ako iné dostupné lieky na liečenie astmy, a nemajú teda úlohu pri rutinnom ovládaní astmy. Spomínajú sa ale v zmysle odporu proti tvrdeniu sprievodných inzerátov, že antihistamíny nesmú byť používané u pacientov s astmou. Ich použitie u pacientov s alergiami horných dýchacích ciest nie je kontrandikované, keď má pacient astmu a na astmu môžu mať tiež prospešný účinok.Antihistamines are weak bronchodilators and newer agents, many of which are not available in the United States, have some anti-inflammatory effects. They are not as effective as other available asthma medications and therefore have no role in the routine control of asthma. However, they refer to resistance to the assertions of accompanying advertisements that antihistamines should not be used in patients with asthma. Their use in patients with upper respiratory allergies is not contraindicated when the patient has asthma and may also have a beneficial effect on asthma.
Štúdie uskutočnené s bežným liečebným dávkovaním sedatívneho antihistamínového lieku cetirizinu pri alergickej rinitíde zahrňujú štúdie uvádzané v nasledujúcich článkoch :Studies conducted with a conventional therapeutic dose of the sedative antihistamine cetirizine in allergic rhinitis include the studies listed in the following articles:
G. Bruttman et al., „Protective El effect of Cetirizine in Patiens Suffering from Polien Asthma, Annals of Alergy, zv.64, str. 224-228 (1990), J. H. Dijkman et al., „Prophylactic Treatment of Grass Pollen-Induced Asthma with Cetirizine, Clinical and Experimental Ällergy, zv. 20, str. 483-490 (1990), J.G. Bruttman et al., "Protective El Effect of Cetirizine in Patiens Suffering from Polien Asthma, Annals of Alergy, Vol.64, p. 224-228 (1990), J. H. Dijkman et al., &Quot; Prophylactic Treatment of Grass Pollen-Induced Asthma with Cetirizine, Clinical and Experimental Allergy, Vol. 20, p. 483-490 (1990) J.
A. Grant et al., „Cetirizine in Patients with Seasonal Rhinitis and Concominant Asthma : Prospective, Randomized, PlaceboControlled Trial, The Journal of Allergy and Clinical Immunology, zv. 95, str. 923-932 (1995), a D. W. Aaronson, „Evaluation of Cetirizine in Patients with Allergic Rhinitis and PeΗ rennial Asthma, Annals of Alergy, Asthma and Immunology, zv. 76, str, 440-446 (1996). Všeobecne bolo zistené, že cetiridin spôsobil určité zlepšenie astmatických príznakov, ako je ťažoba na hrudi, chripenie, krátenie dychu a kašel, súčasne so zmiernením príznakov rinitídy. Nezistilo sa však žiadne výzr namné zlepšenie pulmonárnej funkcie, meranej FEV hodnotami a inými parametrami.Grant et al., "Cetirizine in Patients with Seasonal Rhinitis and Concominant Asthma: Prospective, Randomized, Placebo Controlled Trial, The Journal of Allergy and Clinical Immunology, Vol. 95, p. 923-932 (1995), and D. W. Aaronson, "Evaluation of Cetirizine in Patients with Allergic Rhinitis and Pennial Asthma, Annals of Alergy, Asthma and Immunology, Vol. 76, pp. 440-446 (1996). In general, cetiridine has been found to cause some improvement in asthmatic symptoms such as chest pain, wheezing, shortness of breath and cough, while reducing the symptoms of rhinitis. However, no significant improvement in pulmonary function as measured by FEV values and other parameters was found.
Študovaný bol tiež terferadin, ako uvádza A. Taytard et al., „Treatment of Bronchial Asthma with Terfendine; a Randomized Controlled Trial, British Journal of Clinical Pharmacology, zv. 24, str. 743-746 (1987), P. Rafferty et al., „Terfenadine, a Potent Histamíne Ηχ-Receptor Antagonist in Treatment of Grass Polien Sensitive Asthma, British Journal of Clinical Pharmacology, zv. 30, str. 229-235 (1990), a R. Wood-Baker et al., „A Double-Blind, Placebo Controlled Study of the Effect of the Specific Histamíne Ηχ-Receptor Antagonist, Terfenadine, in Chronic Severe Asthma, British Journal of Clinical Pharmacology, zv. 39, str. 671-675 (1995). Dvojnásobok dávky bežnej pri alergickej rinitíde, alebo 120 mg terfenadinu dvakrát denne, mal slabý pozitívny účinok na pulmonárnu funkciu. Dávkový režim použitý Raffertym et al., 180 miligramov trikrát denne, však mal zvýšené hodnoty PEF o 5,5 percent ráno a 6,2 percent večer. Rutinné podávanie abnormálne vysokých dávok by nebolo rozumné pre dobre známy kardiotoxický potenciál tohto lieku.Terferadine has also been studied, as reported by A. Taytard et al., &Quot; Treatment of Bronchial Asthma with Terfendine; and Randomized Controlled Trial, British Journal of Clinical Pharmacology, Vol. 24, p. 743-746 (1987), P. Rafferty et al., "Terfenadine, and Potent Histamine Ηχ-Receptor Antagonist in the Treatment of Grass Polien Sensitive Asthma, British Journal of Clinical Pharmacology, Vol. 30, p. 229-235 (1990), and R. Wood-Baker et al., "A Double-Blind, Placebo Controlled Study of the Effect of the Specific Histamine-Receptor Antagonist, Terfenadine, in the Chronic Severe Asthma, British Journal of Clinical Pharmacology" , vol. 39, p. 671-675 (1995). Twice the dose common to allergic rhinitis, or 120 mg terfenadine twice daily, had a weak positive effect on pulmonary function. However, the dosing regimen used by Rafferty et al., 180 milligrams three times a day, had elevated PEF values of 5.5 percent in the morning and 6.2 percent in the evening. Routine administration of abnormally high doses would not be reasonable for the well-known cardiotoxic potential of this drug.
A. Dirksen et. al., „Effect of a Non-Sedative Anthistaminic (Loratadine) in Moderate Asthma, Ällergy, zv. 44. str. 566-571 (1989) oznamujú výsledky štúdie, v ktorej sa astmatikom podávali dávky loratadinu ako pri normálnom liečení rinitídy (10 miligramov, raz denne). Pacienti vykazovali zmenšenie príznakov astmy, ale sa ukázalo len malé zlepšenie pulmonárnej funkcie, ktorá bola popísaná ako štatisticky bezvýznamná.A. Dirksen et. al., "Effect of a Non-Sedative Anthistaminic (Loratadine) in Moderate Asthma, Alergy, Vol. 44. p. 566-571 (1989) report the results of a study in which asthmatics were given doses of loratadine as in the normal treatment of rhinitis (10 milligrams, once daily). Patients showed a reduction in asthma symptoms, but showed little improvement in pulmonary function, which was described as statistically insignificant.
Pri liečbe alergickej rinitídy sa často používajú dekons gestantné lieky. Najdôležitejší z nich sú symptomimetické amíny, ktoré majú α-adrenergickú stimulačnú aktivitu. Spomedzi používanými, orálne podávanými činidlami sú fenylpropanolamín, efedrin a pseudoefedrin. Dekongestanty sa dlho používajú v kombinácii s antihistamínmi na liečenie alergických a iných foriem rinitídy a niektoré z horeuvedených publikácií týkajúcich sa štúdií cetirizinu a terfenadinu ukazujú, že pacientom v antihistaminových klinických štúdiách bolo dovolené používať pseudoefedrin na ďalšie zmierňovanie príznakov. Tomuto používaniu však nemožno pripisovať žiadnu neočakávanú úspešnosť.In the treatment of allergic rhinitis, decons are used. The most important of these are symptomimetic amines that have α-adrenergic stimulatory activity. Among the orally administered agents used are phenylpropanolamine, ephedrine and pseudoephedrine. Decongestants have long been used in combination with antihistamines to treat allergic and other forms of rhinitis, and some of the above-mentioned publications on cetirizine and terfenadine studies indicate that patients in antihistamine clinical trials were allowed to use pseudoephedrine to further alleviate symptoms. However, no unexpected success can be attributed to this use.
Podstata vynálezuSUMMARY OF THE INVENTION
Vynález zahrňuje spôsob na zlepšenie pulmonárnej funkcie pacienta trpiaceho astmou, pričom sa pacientovi podáva loratadin v množstvách, ktorý sú bežne účinné pri liečení rinitídy a dekongestantov.The invention encompasses a method for improving pulmonary function of an asthma sufferer by administering to the patient loratadine in amounts that are normally effective in treating rhinitis and decongestants.
Výhodným dekongestantom je pseudoefedrin a výhodná denná liečba na dosiahnutie požadovaných výsledkov podľa vynálezu zahrňuje 10 miligramov loratadinu a jedno z : 240 miligramov pseudoefedrinu, podaného v prostriedku s predĺženým uvoľňovaním, vhodnom pre 24-hodinovú účinnosť, alebo dve denné dávky s 5 miligramami loratidinu a 120 miligramami pseudoefedrinu, podaného v prostriedku s predĺženým uvoľňovaním, vhodnom pre 12hodinovú účinnosť, alebo až do štyroch rozdelených dávok v priebehu 24 hodín s prostriedkom pre okamžité uvoľnenie, ktoré dávajú v súhrne 10 mg loratadinu a 240 miligramov pseudoefedrinu. Zvlášť v prostriedkoch s okamžitým uvoľňovaním môžu byť jednotlivé lieky podávané zvlášť, alebo v kombinovanej dávkovacej forme.A preferred decongestant is pseudoephedrine, and preferred daily treatment to achieve the desired results of the invention comprises 10 milligrams of loratadine and one of: 240 milligrams of pseudoephedrine administered in a sustained release formulation suitable for 24-hour efficacy, or two daily doses of 5 milligrams of loratidine and 120 milligrams of pseudoephedrine administered in a sustained release formulation suitable for 12-hour efficacy, or up to four divided doses over 24 hours with an immediate release formulation that give a total of 10 mg of loratadine and 240 milligrams of pseudoephedrine. Particularly in immediate release formulations, the individual medicaments may be administered separately or in a combined dosage form.
Stručný popis obrázkovBrief description of the pictures
Obr. 1 je grafické znázornenie ranných PEF údajov, získa6 ných v klinickom teste príkladu uskutočnenia vynálezu.Fig. 1 is a graphical representation of morning PEF data obtained in a clinical trial of an exemplary embodiment of the invention.
Obr. 2 je grafické znázornenie večerných PEF údajov, získaných v klinickom teste príkladu uskutočnenia vynálezu.Fig. 2 is a graphical representation of evening PEF data obtained in a clinical trial of an exemplary embodiment of the invention.
Obr. 3 je grafické znázornenie FEV údajov, získaných v klinickom teste príkladu uskutočnenia vynálezu.Fig. 3 is a graphical representation of FEV data obtained in a clinical trial of an exemplary embodiment of the invention.
Podrobný popis vynálezuDETAILED DESCRIPTION OF THE INVENTION
Odkaz na „množstvá, ktoré sú bežne účinné pri liečení rinitídy pri lieku je mienený tak, aby označoval tie dávky, ktoré sú povolené hociktorou relevantnou kontrolnou inštitúciou, ako je FDA (United States Food and Drug Administration) , na použitie pri liečbe príznakov alergickej rinitídy. Odkaz na „zlepšenie pulmonárnej funkcie je mienený tak, že zahrňuje ulahčenie procesov výmeny plynov v plúcach, zvlášť keď sa prejaví klinicky zlepšením meraných hodnôt FEV alebo PEF u pacienta; takéto zlepšenie je bežne sprevádzané znížením pacientovho vnímania krátkosti dychu.The reference to "amounts that are normally effective in the treatment of rhinitis in a medicinal product is intended to indicate those doses that are authorized by any relevant control body, such as the FDA (United States Food and Drug Administration), for use in the treatment of symptoms of allergic rhinitis . The reference to "improvement in pulmonary function is meant to include facilitating lung gas exchange processes, especially when it manifests clinically an improvement in the patient's FEV or PEF measurement; such improvement is commonly accompanied by a reduction in the patient's perception of shortness of breath.
Loratadin, chemicky etyl-4-(8-chlór-5,6-dihydro-llH-benzo [5,6] cyklohepta[1,2-b]pyridín-ll-ylidén)-1-piperidín-karboxylát, s empirickým vzorcom C22H23CIN2O2 a molekulovou hmotnosťou 382,89, je velmi používaný nesedatívny antihistamínový liek s výborným profilom bezpečnosti. Aktívny liek a jeho prostriedky sú popísané v US patente 4 282 233, Vilanimu. Liek možno ľahko pripraviť podľa postupu popísaného v US patente 4 731 447, Schumacherovi et al. Pre účely vynálezu môže byť loratadin podávaný v niekoľkých dávkovacích formách, zahrňujúcich, ale bez obmedzenia, tabletky, kapsule, sirupy alebo injekčné : Ako pri väčšine liekov, orálne podávanie vo forme tabletiek alebo kapsúl je výhodné pre pacientove pohodlie.Loratadine, chemically ethyl 4- (8-chloro-5,6-dihydro-11H-benzo [5,6] cyclohepta [1,2-b] pyridin-11-ylidene) -1-piperidine carboxylate, with empirical formula C22H23CIN2O2 and a molecular weight of 382.89, is a widely used non-sedating antihistamine drug with an excellent safety profile. The active drug and its compositions are described in US Patent 4,282,233 to Vilanim. The drug can be readily prepared according to the procedure described in U.S. Patent 4,731,447 to Schumacher et al. For the purposes of the invention, loratadine may be administered in several dosage forms, including, but not limited to, tablets, capsules, syrups, or injectables: As with most medicaments, oral administration in the form of tablets or capsules is preferred for patient convenience.
Účinná antihistamínová dávka loratadinu je v rozmedzí od asi 5 do 40 miligramov denne. Pre systémové polčasy loratadinu a jeho aktívnych metabolitov môže byť denná dávka podávaná raz za 24 hodín alebo rozdelená na 2, 3 alebo 4 časti výhodne rovnaké, na podávanie zodpovedajúce dávkovaniu dekongestantného lieku. Typická denná dávka loratadinu na odstránenie príznakov alergickej rinitídy je 10 miligramov. Spoločnosť Schering Corporation z Kenilworthu, New Jersey, predáva 10 miligramové tabletky pod názvom CLARITIN®.An effective antihistamine dose of loratadine is in the range of about 5 to 40 milligrams per day. For systemic half-lives of loratadine and its active metabolites, the daily dose may be administered once every 24 hours or divided into 2, 3 or 4 portions, preferably the same, for administration corresponding to the dosage of the decongestant drug. A typical daily dose of loratadine to eliminate the symptoms of allergic rhinitis is 10 milligrams. Schering Corporation of Kenilworth, New Jersey sells 10 milligram tablets under the name CLARITIN®.
Užitočné dekongestantné lieky zahrňujú miestne dekongestanty a systémové dekongestanty. Miestne dekongestanty sú typicky podávané vo forme kvapiek alebo aerosolov ako sú nosné .'reje a obsahujú také lieky, ako sú oxymetazolin, fenylefrin, naíazolin, xylometazolin, efedrin, epinefrin, metylhexanamín, tetrahydrozolin a xylometazolin. Miestne dekongestanty nie sú výhodné na dlhodobú terapiu pre prípadný výskyt rinitis medicamentosa, ktorú bežne možno liečiť len prerušením podávania lieku.Useful decongestant drugs include topical decongestants and systemic decongestants. Topical decongestants are typically administered in the form of drops or aerosols such as nasal carriers and contain such drugs as oxymetazoline, phenylephrine, naphazoline, xylometazoline, ephedrine, epinephrine, methylhexanamine, tetrahydrozoline, and xylometazoline. Local decongestants are not preferred for long-term therapy for the possible occurrence of rhinitis medicamentosa, which can normally be treated only by discontinuing the drug.
Vhodné systémové dekongestantné liekové zlúčeniny pre prax podľa vynálezu zahrňujú symptomimetické amíny fenylpropanolamín, efedrin, pseudoefedrin a fenylefrin, pričom odkaz na liek špecificky zahrňuje jeho farmaceutický prijateľnú sol, ak je potrebná. Najviac z nich je používaný pseudoefedrin, pre jeho rovnováhu medzi účinnosťou a bezpečnosťou. Na formuláciu prostriedkov sa používa jeho hydrochlorid, sulfát alebo iná, vo vode rozpustná sol. Pseudoefedrin sulfát je chemicky [S-(R*, R*)]-α-[1(metylamino)etyl]benzénmetanol sulfát s empirickým vzorcom (C10H15NO) 2*H2SO4, a molekulovou hmotnosťou 428, 54. Extrakcia tejto zlúčeniny z Ma Huang a chemická syntéza danej zlúčeniny sú v odbore dobre známe. Pre účely vynálezu môžu byť pseudoefedrinové soli podávané v ktorejkoľvek z niekoľkých dávkovacích foriem, vrátane, ale bez obmedzenia, tabletiek, kapsúl, sirupov alebo injekčné : ako u väčšiny liekov, orálne podávanie vo forme tabletiek alebo kapsúl je výhodné pre pacientovo pohodlie.Suitable systemic decongestant drug compounds for practice of the invention include the symptomimetic amines phenylpropanolamine, ephedrine, pseudoephedrine, and phenylephrine, and reference to the drug specifically includes a pharmaceutically acceptable salt thereof, if necessary. Most of them are used pseudoephedrine, for its balance between efficacy and safety. A hydrochloride, sulfate or other water-soluble salt thereof is used to formulate the compositions. Pseudoephedrine sulfate is chemically [S- (R *, R *)] - α- [1 (methylamino) ethyl] benzenemethanol sulfate with an empirical formula (C10H15N) 2 * H 2 SO 4, and the molecular weight 428, 54. The extraction of this compound from Ma Huang and chemical synthesis of the compound are well known in the art. For purposes of the invention, pseudoephedrine salts may be administered in any of several dosage forms, including but not limited to tablets, capsules, syrups, or injectables: as with most drugs, oral administration in the form of tablets or capsules is preferred for patient convenience.
Typicky sa bude pseudoefedrin sulfát alebo hydrochlorid podávať dospelým v denných dávkach 120 až 360 miligramov a deťom v denných dávkach 60 až 180 miligramov na uvoľnenie kongescie pri alergickej rinitíde. Systémový polčas pseudoefedrinu je však podstatne kratší u loratadinu. V prostriedkoch na okamžité uvoľnenie sa bežne podávajú jednotlivé dávky v množstve 60 miligramov dospelému pacientovi štyrikrát v každom 24-hodinovom období. Sú však známe pevné prostriedky na predľženie uvoľňovania, keď napríklad 120 miligramov lieku je účinné 12 hodín a 240 miligramov účinkuje až 24 hodín.Typically, pseudoephedrine sulfate or hydrochloride will be administered to adults at daily doses of 120 to 360 milligrams and to children at daily doses of 60 to 180 milligrams to release congestion in allergic rhinitis. However, the system half-life of pseudoephedrine is significantly shorter for loratadine. In immediate release formulations, single doses of 60 milligrams are routinely administered to an adult patient four times in each 24-hour period. However, solid sustained release formulations are known where, for example, 120 milligrams of drug are effective for 12 hours and 240 milligrams are effective for up to 24 hours.
Nie je podstatné, aby sa loratadin a dekongestant dávkovali spolu. Napríklad : loratadin môže byť podávaný raz denne, ale dekongestant je podávaný častejšie na udržanie terapeutickej systémovej hladiny lieku. Pokiaľ sú lieky dávkované spoločne, nie je potrebné, aby boli prítomné v rovnakom prostriedku alebo dávkovej forme.It is not essential that loratadine and decongestant be co-administered. For example, loratadine may be administered once daily, but decongestant is administered more frequently to maintain the therapeutic systemic level of the drug. When the drugs are co-administered, they do not need to be present in the same composition or dosage form.
Prostriedky, ktoré kombinujú dávky antihistaminických liekov a dekongestantných liekov sú v odbore dobre známe. Pre loratadin zahrnujú prostriedok, ktorý obsahuje 5 miligramov loratadinu a 60 miligramov pseudoefedrin sulfátu na okamžité uvoľnenie poťahu tabletky, spolu so 60 miligramami pseudoefedrinu, ktorý sa uvolňuje riadenou rýchlosťou z erodovatelného nosiča tabletky na poskytnutie účinnosti počas 12 hodinovom období. Tento užitočný produkt je v Spojených štátoch komerčne dostupný od spoločnosti Schering Corporation z Kenilworthu, New Jersey, pod názvom CLARITIN-D® 12 HOUR. Iný prostriedok obsahuje 10 miligramov loratadinu na okamžité uvoľnenie z poťahu tabletky spolu s 240 miligramami pseudoefedrinu, ktorý sa uvolňuje riadenou rýchlosťou z erodovatelného nosiča tabletky na poskytnutie účinnosti počas 24 hodinového obdobia. Táto technika je popísaná v US patente 5 314 697, Kwanovi et al., a užitočný produkt je v Spojených štátoch komerčne dostupný od spoločnosti Schering Corporation z Kenilworthu, New Jersey, pod názvom CLARITIN-D® 24 HOUR. Také kombinované prostriedky väčšine pacientov budú vyhovovať pre pohodlnosť.Compositions that combine doses of antihistaminic drugs and decongestant drugs are well known in the art. For loratadine, the formulation comprises 5 milligrams of loratadine and 60 milligrams of immediate release tablet pseudoephedrine sulfate, along with 60 milligrams of pseudoephedrine, which is released at a controlled rate from the erodible tablet carrier to provide efficacy over a 12 hour period. This useful product is commercially available in the United States from Schering Corporation of Kenilworth, New Jersey, under the name CLARITIN-D® 12 HOUR. Another formulation contains 10 milligrams of immediate release loratadine from the tablet coating along with 240 milligrams of pseudoephedrine that is released at a controlled rate from the erodible tablet carrier to provide efficacy over a 24 hour period. This technique is described in U. S. Patent 5,314,697 to Kwan et al., And a useful product is commercially available in the United States from Schering Corporation of Kenilworth, New Jersey, under the name CLARITIN-D® 24 HOUR. Such combination formulations will suit most patients for convenience.
Tento vynález bude ďalej vysvetlený pomocou odkazu na nasledujúci príklad, ktorý žiadnym spôsobom neobmedzuje pripojené nároky.The invention will be further elucidated by reference to the following example, which in no way limits the appended claims.
Príklad uskutočnenia vynálezuDETAILED DESCRIPTION OF THE INVENTION
Bola uskutočnená klinická skúška, v ktorej bolo 193 dospelých pacientov trpiacich astmou aj rinitídou, náhodne usporiadaných, pričom dostávali už hore popísaný produkt CLARITIN-D® -12 HOUR alebo placebu, dvakrát denne šesť týždňov počas jesennej alergickej sezóny. Všetci pacienti užívali, a to aj počas štúdie, bronchodilatačný liek albuterol z tlakovaného aerosólového inhalátora s odmeranou dávkou, ako mali predpísané lekárom na kontrolu astmatických príznakov. V priebehu štúdie nemali pacienti povolené užívať žiadny iný liek na rinitídu alebo astmu.A clinical trial was conducted in which 193 adult patients with asthma and rhinitis were randomized to receive the CLARITIN-D®-12 HOUR or placebo product described above twice a day for six weeks during the autumn allergic season. All patients were taking the bronchodilator albuterol from a pressurized metered-dose inhaler, even during the study, as prescribed by a physician to control asthma symptoms. During the study, patients were not allowed to take any other medicine for rhinitis or asthma.
Pacientov pred začiatkom štúdie vyhodnotili, medzi iným, meraním FEV a PEF rýchlosti na vytvorenie údajov základnej čiary, a hodnotenie bolo v priebehu štúdie opakované každý týždeň.Patients were evaluated before baseline, inter alia, by measuring FEV and PEF rate to produce baseline data, and the assessment was repeated weekly throughout the study.
Pacienti, ktorí dostávali uvedenú kombináciu liekov bolo zistené, že im značne znižuje príznaky ako rinitídy, tak astmy, v porovnaní s pacientami, ktorí dostávali len placebo.Patients receiving the combination of drugs were found to significantly reduce the symptoms of both rhinitis and asthma compared to patients who received only placebo.
Obr. 1 ukazuje výsledky ranného merania PEF rýchlostí u pacientov, ktorí dostávali loratadin a pseudoefedrin sulfát (plná čiara) a placebo (bodkovaná čiara). Na zvislej ose je stredná zmena PEF rýchlosti od hodnôt základnej čiary, vyjadrená v litroch za minútu. V priebehu štúdie nastalo jasné, štatisticky významné zlepšenie vďaka podávaniu kombinovaných liekov.Fig. 1 shows the results of an early measurement of PEF rates in patients receiving loratadine and pseudoephedrine sulfate (solid line) and placebo (dotted line). On the vertical axis, the mean change in PEF velocity from baseline values, expressed in liters per minute. There was a clear, statistically significant improvement over the course of the study due to the combination drugs.
Obr. 2 je podobnou reprezentáciou výsledkov z večerného merania PEF rýchlostí u pacientov, ktorých skupiny sú identifikované hore. Podobne jasné, štatisticky významné zlepšenie v priebehu štúdie je výsledkom podávania danej kombinácie liekov.Fig. 2 is a similar representation of the results of evening PEF measurements in patients whose groups are identified above. Similarly, a statistically significant improvement over the course of the study is due to the administration of the combination of drugs.
Obr. 3 reprezentuje ďalšie výsledky štúdie, ako boli vytvorené meraním FEV v prvej sekunde (,,FEVi„) . Na zvislej ose je ukázaná stredná zmena od základnej čiary FEVi hodnôt, vyjadrená v litroch. Údaje od pacientov, ktorí dostávali loratadin a pseudoefedrin sú identifikované plnými stĺpcami, ale údaje od pacientov, ktorí dostávali len placebo, sú predstavované prázdnymi stĺpcami. Velmi jasné, štatisticky významné zlepšenie v priebehu štúdie je výsledkom podávania uvedenej kombinácie liekov.Fig. 3 represents further study results as generated by FEV measurement in the first second ("FEVi"). The vertical axis shows the mean change from the baseline of FEVi values, expressed in liters. Data from patients receiving loratadine and pseudoephedrine are identified by solid bars, but data from patients receiving only placebo are represented by empty bars. A very clear, statistically significant improvement over the course of the study results from the administration of the combination of drugs.
Veľkosť zlepšenia v pulmonárnej funkcii bude tu významná pre dobrý stav asmatických pacientov, bez ohladu na to, či pacient trpí rinitídou alebo nie.The magnitude of the improvement in pulmonary function will be significant here for the good condition of asmatic patients, regardless of whether the patient is suffering from rhinitis or not.
Claims (12)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73966996A | 1996-10-31 | 1996-10-31 | |
| PCT/US1997/019158 WO1998018470A1 (en) | 1996-10-31 | 1997-10-29 | Composition, for the treatment of asthma, containing loratadine and a decongestant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK54599A3 true SK54599A3 (en) | 2000-08-14 |
Family
ID=24973307
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK545-99A SK54599A3 (en) | 1996-10-31 | 1997-10-29 | Composition for the treatment of asthma, containing loratadine and a decongestant |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0941091A1 (en) |
| JP (1) | JP2000505104A (en) |
| KR (1) | KR20000052922A (en) |
| CN (1) | CN1235545A (en) |
| AR (1) | AR008908A1 (en) |
| AU (1) | AU731756B2 (en) |
| BR (1) | BR9712705A (en) |
| CA (1) | CA2268546A1 (en) |
| CO (1) | CO4910128A1 (en) |
| CZ (1) | CZ150999A3 (en) |
| HU (1) | HUP9904075A3 (en) |
| ID (1) | ID23431A (en) |
| IL (1) | IL129662A0 (en) |
| NO (1) | NO992062L (en) |
| NZ (1) | NZ335078A (en) |
| PE (1) | PE11399A1 (en) |
| PL (1) | PL333056A1 (en) |
| SK (1) | SK54599A3 (en) |
| TR (1) | TR199901003T2 (en) |
| WO (1) | WO1998018470A1 (en) |
| ZA (1) | ZA979731B (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999021556A1 (en) * | 1997-10-29 | 1999-05-06 | J-Med Pharmaceuticals, Inc. | Antihistamine/decongestant regimens for treating rhinitis |
| US6132758A (en) | 1998-06-01 | 2000-10-17 | Schering Corporation | Stabilized antihistamine syrup |
| IT1303671B1 (en) * | 1998-07-28 | 2001-02-23 | Nicox Sa | SALTS OF NITRIC ACID WITH ACTIVE DRUGS IN THE TREATMENT OF DISEASES OF THE RESPIRATORY SYSTEM |
| PE20001070A1 (en) * | 1998-09-10 | 2000-10-19 | Schering Corp | METHODS AND COMPOSITIONS TO TREAT SINUSITIS, OTITIS MEDIA AND OTHER RELATED DISORDERS USING ANTIHISTAMINES |
| US6521254B2 (en) | 1998-12-07 | 2003-02-18 | J-Med Pharmaceuticals, Inc. | Single-dose antihistamine/decongestant formulations for treating rhinitis |
| AU2697100A (en) * | 1999-02-23 | 2000-09-14 | Yuhan Corporation | Pharmaceutical capsule compositions containing loratadine and pseudoephedrine |
| KR100505899B1 (en) * | 1999-02-23 | 2005-08-01 | 주식회사유한양행 | Pharmaceutical capsule compositions containing loratadine and pseudoephedrine |
| AU3924500A (en) * | 1999-03-29 | 2000-10-16 | Schering Corporation | Methods and compositions for treating allergic and related disorders using fluorinated descarboethoxyloratadine |
| AU2277101A (en) * | 1999-12-20 | 2001-07-03 | Schering Corporation | Stable extended release oral dosage composition |
| WO2001045676A2 (en) * | 1999-12-20 | 2001-06-28 | Schering Corporation | Extended release oral dosage composition |
| JP5592042B2 (en) * | 2000-04-14 | 2014-09-17 | ジェイ−メド ファーマシューティカルズ，インコーポレーティッド | Single dose antihistamine / decongestant formulation for the treatment of rhinitis |
| PE20020055A1 (en) * | 2000-05-25 | 2002-02-12 | Schering Corp | STABLE LIQUID AND SOLID FORMULATIONS INCLUDING A NON-SEDATING ANTIHISTAMINE AND A NASAL DECONGESTANT |
| BR0210534A (en) * | 2001-06-20 | 2004-06-22 | Schering Corp | Antihistamines for the treatment of nasal congestion and nasal obstruction |
| RU2423979C2 (en) * | 2005-06-17 | 2011-07-20 | АФТ Фармасьютикалз Лимитед | Novel pharmaceutic composition and its application in method of treatment of patients with hyperaemia and edema of mucous membrane of upper airways |
| EP1896022B1 (en) | 2005-06-17 | 2012-10-31 | AFT Pharmaceuticals Limited | Novel pharmaceutical composition and its use in a method for treatment of patients with upper respiratory mucosal congestion |
| AU2007254821B2 (en) * | 2006-06-01 | 2013-11-14 | Bayer Consumer Care Ag | Sustained release pharmaceutical formulation comprising phenylephrine |
| NZ573174A (en) * | 2006-06-01 | 2012-01-12 | Msd Consumer Care Inc | Sustained release pharmaceutical dosage form containing phenylephrine |
| KR101540191B1 (en) * | 2014-02-24 | 2015-07-28 | 성균관대학교산학협력단 | Composition comprising Loratadine for anti-inflammation |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1110397A (en) * | 1964-10-02 | 1968-04-18 | Mead Johnson & Co | Ephedrine composition |
| US4990535A (en) * | 1989-05-03 | 1991-02-05 | Schering Corporation | Pharmaceutical composition comprising loratadine, ibuprofen and pseudoephedrine |
| US5407686A (en) * | 1991-11-27 | 1995-04-18 | Sidmak Laboratories, Inc. | Sustained release composition for oral administration of active ingredient |
| US5314697A (en) * | 1992-10-23 | 1994-05-24 | Schering Corporation | Stable extended release oral dosage composition comprising loratadine and pseudoephedrine |
| US5595997A (en) * | 1994-12-30 | 1997-01-21 | Sepracor Inc. | Methods and compositions for treating allergic rhinitis and other disorders using descarboethoxyloratadine |
-
1997
- 1997-10-29 CN CN97199404A patent/CN1235545A/en active Pending
- 1997-10-29 PL PL97333056A patent/PL333056A1/en unknown
- 1997-10-29 WO PCT/US1997/019158 patent/WO1998018470A1/en not_active Ceased
- 1997-10-29 SK SK545-99A patent/SK54599A3/en unknown
- 1997-10-29 EP EP97912874A patent/EP0941091A1/en not_active Withdrawn
- 1997-10-29 ID IDW990280D patent/ID23431A/en unknown
- 1997-10-29 IL IL12966297A patent/IL129662A0/en unknown
- 1997-10-29 PE PE1997000968A patent/PE11399A1/en not_active Application Discontinuation
- 1997-10-29 TR TR1999/01003T patent/TR199901003T2/en unknown
- 1997-10-29 CO CO97063641A patent/CO4910128A1/en unknown
- 1997-10-29 ZA ZA9709731A patent/ZA979731B/en unknown
- 1997-10-29 CZ CZ991509A patent/CZ150999A3/en unknown
- 1997-10-29 HU HU9904075A patent/HUP9904075A3/en unknown
- 1997-10-29 BR BR9712705-1A patent/BR9712705A/en not_active Application Discontinuation
- 1997-10-29 AR ARP970105033A patent/AR008908A1/en not_active Application Discontinuation
- 1997-10-29 CA CA002268546A patent/CA2268546A1/en not_active Abandoned
- 1997-10-29 KR KR1019990703790A patent/KR20000052922A/en not_active Ceased
- 1997-10-29 NZ NZ335078A patent/NZ335078A/en unknown
- 1997-10-29 JP JP10520579A patent/JP2000505104A/en active Pending
- 1997-10-29 AU AU49953/97A patent/AU731756B2/en not_active Ceased
-
1999
- 1999-04-29 NO NO992062A patent/NO992062L/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| PL333056A1 (en) | 1999-11-08 |
| ID23431A (en) | 2000-04-20 |
| NO992062D0 (en) | 1999-04-29 |
| PE11399A1 (en) | 1999-02-09 |
| HUP9904075A2 (en) | 2000-05-28 |
| NZ335078A (en) | 2000-10-27 |
| BR9712705A (en) | 1999-10-26 |
| CZ150999A3 (en) | 1999-10-13 |
| EP0941091A1 (en) | 1999-09-15 |
| AU4995397A (en) | 1998-05-22 |
| AU731756B2 (en) | 2001-04-05 |
| CN1235545A (en) | 1999-11-17 |
| AR008908A1 (en) | 2000-02-23 |
| HUP9904075A3 (en) | 2002-02-28 |
| ZA979731B (en) | 1998-04-29 |
| TR199901003T2 (en) | 1999-07-21 |
| WO1998018470A1 (en) | 1998-05-07 |
| JP2000505104A (en) | 2000-04-25 |
| CA2268546A1 (en) | 1998-05-07 |
| CO4910128A1 (en) | 2000-04-24 |
| NO992062L (en) | 1999-04-29 |
| KR20000052922A (en) | 2000-08-25 |
| IL129662A0 (en) | 2000-02-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK54599A3 (en) | Composition for the treatment of asthma, containing loratadine and a decongestant | |
| Aaronson | Evaluation of cetirizine in patients with allergic rhinitis and perennial asthma | |
| JP2022003100A (en) | Nasal administration composition for treating neurological and neurodegenerative diseases and disorders | |
| US20030236275A1 (en) | Treatment methods of nasal congestion and nasal obstruction | |
| US6432972B2 (en) | Treating allergic and inflammatory conditions | |
| KR20180033201A (en) | Antitussive compositions and methods | |
| KR101071798B1 (en) | New synergistic combination comprising roflumilast and formoterol | |
| WO2008085392A1 (en) | Methods for treating nasal congestion in hepatically impaired patients | |
| AU2001247867B2 (en) | Composition for treating allergic and inflammatory conditions with cough containing a non-sedating histamine and an expectorant | |
| JP2004534820A (en) | Antihistamines for the treatment of nasal congestion and nasal obstruction | |
| MXPA99003936A (en) | Composition, for the treatment of asthma, containing loratadine and a decongestant | |
| WO2002047689A2 (en) | Use of cetirizine or efletirizine for preventing urticaria | |
| JP2003509458A (en) | Treatment of allergic and inflammatory conditions | |
| AU2001247867A1 (en) | Composition for treating allergic and inflammatory conditions with cough containing a non-sedating histamine and an expectorant | |
| AU2002315357A1 (en) | Antihistamines for the treatment of nasal congestion and nasal obstruction | |
| AU2006201218A1 (en) | Treating allergic and inflammatory conditions | |
| HK1081861B (en) | New synergistic combination comprising roflumilast and formoterol |