HRP970419A2 - Medically beneficial preparation for outer use containing amino acids - Google Patents
Medically beneficial preparation for outer use containing amino acidsInfo
- Publication number
- HRP970419A2 HRP970419A2 HRP9602024A HRP970419A HRP970419A2 HR P970419 A2 HRP970419 A2 HR P970419A2 HR P9602024 A HRP9602024 A HR P9602024A HR P970419 A HRP970419 A HR P970419A HR P970419 A2 HRP970419 A2 HR P970419A2
- Authority
- HR
- Croatia
- Prior art keywords
- amino acids
- interferon
- antiviral
- fact
- pct
- Prior art date
Links
- 150000001413 amino acids Chemical class 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 230000009286 beneficial effect Effects 0.000 title abstract 2
- 102000014150 Interferons Human genes 0.000 claims abstract description 24
- 108010050904 Interferons Proteins 0.000 claims abstract description 24
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 22
- 229940079322 interferon Drugs 0.000 claims abstract description 20
- 208000024891 symptom Diseases 0.000 claims abstract description 8
- 230000003602 anti-herpes Effects 0.000 claims abstract description 6
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 6
- 229940024606 amino acid Drugs 0.000 claims description 23
- 235000001014 amino acid Nutrition 0.000 claims description 23
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 9
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 8
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 5
- -1 oxyproline Chemical compound 0.000 claims description 5
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 4
- 230000003389 potentiating effect Effects 0.000 claims description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000003883 ointment base Substances 0.000 claims description 3
- 229940104230 thymidine Drugs 0.000 claims description 3
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 2
- 229960005261 aspartic acid Drugs 0.000 claims description 2
- 235000018417 cysteine Nutrition 0.000 claims description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
- 229960002433 cysteine Drugs 0.000 claims description 2
- 229960003067 cystine Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000002349 favourable effect Effects 0.000 claims 1
- 229960002449 glycine Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000003755 preservative agent Substances 0.000 claims 1
- 230000002335 preservative effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- 208000029433 Herpesviridae infectious disease Diseases 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000003190 augmentative effect Effects 0.000 abstract 1
- 230000001185 psoriatic effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 10
- 241000700605 Viruses Species 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 238000005259 measurement Methods 0.000 description 6
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 229940047124 interferons Drugs 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 241000711975 Vesicular stomatitis virus Species 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- DWBZEJHQQIURML-IMJSIDKUSA-N Asp-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O DWBZEJHQQIURML-IMJSIDKUSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
- FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 description 1
- FKBFDTRILNZGAI-IMJSIDKUSA-N Asp-Cys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(O)=O FKBFDTRILNZGAI-IMJSIDKUSA-N 0.000 description 1
- OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 1
- JAQGKXUEKGKTKX-HOTGVXAUSA-N Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 JAQGKXUEKGKTKX-HOTGVXAUSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000001691 amnion Anatomy 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 108010004073 cysteinylcysteine Proteins 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- XACKNLSZYYIACO-DJLDLDEBSA-N edoxudine Chemical compound O=C1NC(=O)C(CC)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XACKNLSZYYIACO-DJLDLDEBSA-N 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 102000043557 human IFNG Human genes 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 108010003137 tyrosyltyrosine Proteins 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/217—IFN-gamma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Ovim je patentom opisan ljekoviti preparat za vanjsku upotrebu sa sadržajem aminokiselina.
Preparat pripremljen po opisu ovoga patenta uvećava antiviralno i antiinflamatorno djelovanje interferona i analognih spojeva timidina antiherpetičkoga djelovanja, ublažuje simptome psoriaze, nadalje uspješno suzbija infekcije prouzrokovane herpes virusima.
Interferoni su prirodne bjelančevine, koje posjeduju složeno biološko djelovanje. Najznačajnije osobine su im što sprečavaju nastajanje zapaljenja, umnožavanje virusa, diobu stanica i uvećavaju efikasnost ljudskog imunološkog sistema.
Zbog ovih osobina interferona, isti se uspješno primjenjuje u liječničkoj praksi, kao i u terapijskom liječenju raka.
Gore navedene primjene interferona opisane su u slijedećim časopisima: J. biol. Regul. Homeostatic Agents, 1, str. 93 - 99 i 177 - 182, 1987; Intern. J. Cancer, 1987 (Suppl.1.), str. 9 - 13, 1987; J. Interferon Res., Spec. Issue, 1992 Apr., str. 109 - 118.
Primjene interferona pri suzbijanju virusnih infekcija opisane su u slijedećim časopisima: Lancet, i, str. 128, 1976; Transplantation Proc., 21, str. 2429 - 2430, 1989; Interferons in the Treatment of Chronic Virus Infections of the Liver, Pennine Press, Macclesfield, 1990.
Interferoni su uspješni i u suzbijanju simptoma zapaljenja: Neurology, 43, str. 655 - 661, 1993; J. Interferon and Cytokine Res., 15, str. 39 - 45, 1995.
Radi postizanja željenoga terapijskoga efekta, tokom terapije upotrebljavaju se velike doze, koje zbog složenoga biološkog djelovanja interferona, prouzrokuju javljanje neželjenih efekata (J. Rheumatol., 20, str. 83 - 85, 1992; J. Pediatr., 120(3), str. 429 - 431, 1992; Clin. Exp. Immunol., 90(3), str. 363 - 367, 1992).
Mogućnost korištenja interferona u terapijske svrhe znatno ograničava javljanje neželjenih efekata.
Da bi se umanjili neželjeni efekti, u terapijske svrhe interferoni se koriste kombinirano sa raznim preparatima. Postoje različite mogućnosti primjenjivanja kombinirane terapije: davanjem lijekova sličnoga djelovanja može se umanjiti potrebna doza interferona (J. Natl. Cancer Inst., 83, str. 1408 - 1410, 1991); neželjeni efekti mogu se selektivno umanjiti lijekovima suprotnoga djelovanja (J. Biol. Resp. Modifiers, 5, str. 447 - 480, 1986); selektivno se može uvećati terapijski efekat sa potencirajućim agensima kao i sa korištenjem odgovarajućih fizičkih okolnosti, npr. hipertermijom (Proc. Soc. Exp. Biol. Med., 169, str. 413 - 415, 1982).
U stručnoj je literaturi poznato da se u značajnoj mjeri umanjuje terapijsku efikasnost antiherpetičnog djelovanja analognih spojeva timidina (derivati 5'-substituiranog dezoksi-uridina), pošto se u kratkome vremenskome roku javlja rezistencija protiv terapijske doze. Ovako nastali rezistentni virusi otporni su i na spojeve slične kemijske strukture. Korištenjem manjih doza ovih spojeva umanjuje se selektivno djelovanje i mogućnost nastajanja rezistentnih virusa, i ovim putem bi se povećala terapijska vrijednost ovih preparata.
Cilj ovoga izuma je selektivno uvećavanje antiviralnoga djelovanja interferona i antiherpetičkih analognih spojeva timidina potencirajućim dodacima radi umanjivanja efektivne terapijske doze antiviralnih lijekova.
Cilj nam je bio stvoriti takve kombinacije lijekova koje će biti uspješno korištene u slučajevima infekcije herpes virusima, kao i u liječenju kožnih simptoma psoriaze.
Tema naučnoga rada je konstruiranje rastvora i masti za vanjsku upotrebu sa malom dozom (tako nema naželjenih efekata) antiviralnih spojeva (interferon, 5-ethyl-2'-deoxyuridine = EDU, 5-iodo-2'-deoxyuridine = IDU) kombiniranim sa selektivnim potencirajućim komponentama (aminokiselinama) koje uvećavaju antiviralno i antiinflamatorno djelovanje interferona.
Izum se bazira na spoznaji da pojedine aminokiseline 102 - 104 puta uvećavaju antiviralno djelovanje analognih spojeva timidina u slučajevima infekcije herpes virusima, kao i antiviralno i antiinflamatorno djelovanje interferona, a pri tome ne izazivaju promijene u ostalim biološkim efektima interferona. Ovi preparati su uspješni pri liječenju infekcija izazvanim herpes virusima i suzbijanju kožnih simptoma psoriaze.
Subjekt naučnoga rada je ljekoviti preparat za vanjsku upotrebu sa sadržajem aminokiselina koji posjeduje uvećano antiviralno i antiinflamatorno djelovanje i uspješno suzbija kožne simptome psoriaze.
Preparat sadrži dalje navedene aminokiseline kao što su D- ili L-asparaginska kiselina (Asp), cistein (Cys), cistin (cys), glicin (Gly), oksiprolin (Opr), serin (Ser), tirozin (Tyr), zatim interferon ili analogno spoj timidina sa antiherpetičnim djelovanjem - povoljno derivate uridina, farmaceutske dodatke, povoljno rastvarače, konzervacijske agense ili poznate osnove za masti.
Izum će biti predstavljen slijedećim primjerima:
Primjer 1
Pod sterilnim uvjetima pripremljenom 50.000 IU/ml vodenom rastvoru ljudskog interferona alfa (HuIFN-�, komercijalno ime je EGIFERON) dodamo D-asparaginsku kiselinu i L-serin u koncentraciji od 5-5 mg/ml obje aminokiseline. Rastvor je konzerviran saharozom u 20 w/v % koncentraciji.
Primjer 2
Sterilnom 2500 IU/ml vodenom rastvoru nativnog ili rekombinantnog ljudskog interferona gama (HuIFN-�) dodano je u koncentraciji 5-5 mg/ml D-Asp i L-Opr. Rastvor je konzerviran saharozom u 20 w/v % koncentraciji.
Primjer 3
Sterilnom 25 µg/ml vodenom rastvoru IDU-a dodano je u koncentraciji od 25 mg/ml D-Asp. Rastvor je konzerviran saharozom u 20 w/v % koncentraciji.
Primjer 4
Sterilnom 25 µg/ml vodenom rastvoru EDU-a dodano je u koncentraciji od 1 mg/ml L-Ser i 500 IU/ml nativnog ili rekombinantnog HuIFN-�. Rastvor je konzerviran saharozom u 20 w/v % koncentraciji.
Primjer 5
Rastvor pripremljen po opisu u primjeru 1 pod sterilnim uvjetima umiješamo u osnovu za mast (u unguentum hydrophylicum).
Primjer 6
Rastvor pripremljen po opisu u primjeru 2 pod sterilnim uvjetima umiješamo u osnovu za mast opisanom u primjeru 5.
Primjer 7
Antiviralno djelovanje 500 IU/ml HuIFN-� protiv virusa vezikularnog stomatitisa (VSV) ustanovili smo na permanentnoj tkivnoj kulturi ljudskog amnion-epitela (WISH), u prisustvu različitih aminokiselina pod različitim uvjetima. Antiviralni test sastoji se iz tri faze. U prvoj fazi testa razmnožavamo WISH stanice u mikrotitracijskim pločama sa 96 rupica do potpunog jednoslojnoga stadija (monolayer). U rupice stavimo po 100 µl iz članova dvostrukoga razblaženoga reda, damo da odstoji 20 - 24 sati na temperaturi od 37 °C u atmosferi sa 5 % CO2-a (II. faza). Interferonu izložene stanice inficiramo takvom količinom VSV-a, koja u periodu od 24 sata potpuno uništava nezaštićne stanice (III. faza). Referentna točka mjerenja (HuIFN-� titer) je koncentracija interferona koja u periodu od 24 sata točno polovinu (50 %) stanica zaštićuje od uništenja. Pri daljnjim mjerenjima antiviralnog djelovanja koristimo koncentraciju interferona koja je određena kao HuIFN-� titer.
Mjerenja su izvršena:
a) u prisustvu različitih aminokiselina u različitim koncentracijama u drugoj fazi (slika 1)
b) u prisustvu različitih aminokiselina u koncentraciji od 10 mg/ml u fazama I., II., III. (slika 2)
c) u prisustvu različitih aminokiselinskih parova u koncentraciji od po 5-5 mg/ml u II. fazi (tablica 1)
Tablica 1
Antiviralni titer IFN-�-a u prisustvu aminokiselinskih parova u drugoj fazi. Rezultati su dati u postotcima prema kontrolnom mjerenju bez aminokiselina. Moramo primijetiti sinergetsku kooperaciju između Asp-Ser i Ser-Tyr.
[image]
d) u prisustvu različitih aminokiselinskih parova u koncentraciji od po 5-5 mg/ml u III. fazi (tablica 2)
Tablica 2
Antiviralni titer IFN-� u prisustvu aminokiselinskih parova u trećoj fazi. Rezultati su dati u postotcima prema kontrolnom mjerenju bez aminokiselina. Najznačajniji parovi su: Asp-Ser, Asp-Cys, i u dozama od 10 mg/ml Asp, Cys, Tyr, Opr (naročito parovi Asp-Asp, Cys-Cys, Tyr-Tyr, Opr-Opr). Trebamo primijetiti da su uvjeti u trećoj (III.) fazi vrlo slični prirodnome toku infekcije; terapijski agens i virus je u istom vremenu prisutan u ljudskom organizmu.
[image]
Primjer 8
Po opisu u primjeru 7 mjerili smo promjene antiviralnoga titera HuIFN-� u prisustvu aminokiselina (10 mg/ml) u drugoj i trećoj fazi (tablica 3).
Tablica 3
Utjecaj datih aminokiselina u drugoj i trećoj fazi na antiviralan titer HuIFN-�. Trebamo primijetiti da u III. fazi u velikoj mjeri uvećavaju antiviralni titer slijedeće aminokiseline: Asp, Cys i Tyr. Ekstremno uvećanje (180 puta) postiže se Opr-om.
[image]
Primjer 9
Antiviralno djelovanje različitih koncentracija IDU-a protiv ljudskog Herpes simpleks 1. virusa (HSV 1) mjerili smo na permanentnoj tkivnoj kulturi ljudskih tumornih stanica (Hep 2). Stanice razmnožavamo u Petrijevim šalicama do potpunoga jednoslojnoga stadija. Zatim inficiramo stanice sa tolikom količinom virusa (HSV 1), koja u periodu od 72 sata potpuno uništava nezaštićene stanice. Nakon 1 sata na stanice stavimo svježi medij koji sadrži različite količine antiviralnoga spojeva, i držimo stanice u roku od 72 sata na temperaturi od 37 °C u atmosferi sa 5 % CO2. Nastalu količinu virusa ustanovljavamo nakon što od lize stanica odstranimo njihove ostatke i iz čiste tekućine načinimo 10 - terostruki razblaženi red. Potom ustanovimo koji član razblaženoga reda u roku od 72 sata uništava točno polovinu Hep 2 stanica u potpunoj tkivnoj kulturi. Antiviralno djelovanje određujemo iz umanjenja količine nastalih virusa.
Mjerili smo promjenu antiviralnoga djelovanja:
a) u prisustvu 5mg/ml Ser-a (slika 3)
b) u prisustvu 5mg/ml Asp-a (slika 4)
Primjer 10
Po opisu u primjeru 9 mjerili smo antiviralno djelovanje različitih koncentracija EDU-a u prisustvu 5 mg/ml Ser-a i 250 IU/ml HuIFN-� (slika 5).
Primjer 11
Proučavali smo efikasnost preparata pripremljenoga po opisu u primjeru 5 u liječenju herpetičnih infekcija (HSV 1, Herpes zoster) kao i liječenju inflamatornih kožnih simptoma različitoga porijekla. Mjerenje je izvršena na dobrovoljno pristalim pacijentima. Rezultati su dati u tablici 4.
Tablica 4
[image]
Claims (4)
1. Ljekoviti preparat za vanjsku upotrebu, naznačen time što posjeduje povoljno potetencirajuće antiviralno, antiinflamatorno djelovanje, nadalje pogodan je za liječenje kožnih simptoma psoriaze, opisan slijedećim osobinama: sadrži neku od slijedećih aminokiselina: D- ili L-asparaginska kiselina, cistein, cistin, glicin, oksiprolin, serin, tirozin ili mješavinu gore navedenih aminokiselina; po potrebi interferon, antiherpetično analogno spoj timidina, povoljno derivate uridina; poznate farmaceutske dodatke, povoljno razrjeđivač, konzervacijski agens ili osnovu za mast.
2. Ljekoviti preparat pripremljen po opisu u točki 1., naznačen time što sadrži D-asparaginsku kiselinu kao aminokiselinu.
3. Ljekoviti preparat pripremljen po opisu u točki 1., naznačen time što sadrži D-asparaginsku kiselinu i oksiprolin kao aminokiseline.
4. Ljekoviti preparat pripremljen po opisu u točki 1., naznačen time što sadrži serin kao aminokiselinu.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9602024A HUP9602024A3 (en) | 1996-07-25 | 1996-07-25 | Pharmaceutical composition containing aminoacid for external use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP970419A2 true HRP970419A2 (en) | 1998-08-31 |
Family
ID=89994154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP9602024A HRP970419A2 (en) | 1996-07-25 | 1997-07-24 | Medically beneficial preparation for outer use containing amino acids |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6048843A (hr) |
| EP (1) | EP0855915B1 (hr) |
| AT (1) | ATE297752T1 (hr) |
| AU (1) | AU3354997A (hr) |
| CA (1) | CA2232710A1 (hr) |
| DE (1) | DE69733539D1 (hr) |
| HR (1) | HRP970419A2 (hr) |
| HU (1) | HUP9602024A3 (hr) |
| WO (1) | WO1998004280A2 (hr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT886527E (pt) * | 1996-02-28 | 2001-12-28 | Unihart Corp | Composicao farmaceutica que incorpora o interferao alfa humano natural |
| US7396526B1 (en) | 1998-11-12 | 2008-07-08 | Johnson & Johnson Consumer Companies, Inc. | Skin care composition |
| DE60021760T2 (de) | 1999-12-09 | 2006-06-08 | Chiron Corp., Emeryville | Verfahren zur verabreichung von wirkstoffen in das zentrale nervensystem oder lymphsystem |
| US6415797B1 (en) * | 2000-07-07 | 2002-07-09 | First Circle Medical, Inc. | Treatment of human herpesviruses using hyperthermia |
| KR20020027198A (ko) * | 2000-10-02 | 2002-04-13 | 차알스 제이. 메츠 | 염증과 홍반의 완화방법 |
| US6328987B1 (en) * | 2000-11-03 | 2001-12-11 | Jan Marini Skin Research, Inc. | Cosmetic skin care compositions containing alpha interferon |
| EP1377291A2 (de) * | 2001-03-13 | 2004-01-07 | Protagen AG | 1-butansäuderivate wie z.b. carbomethoxypropionylcyanid oder leflunomidderivate und deren therapeutische anwendung |
| DE10112924A1 (de) * | 2001-03-13 | 2002-10-02 | Erich Eigenbrodt | 1-Butansäurederivate, pharmazeutische Zusammensetzungen enthaltend solche Derivate und Verwendungen solcher Derivate |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4710376A (en) * | 1985-02-01 | 1987-12-01 | Interferon Sciences, Inc. | Topical therapeutic composition containing oxidation inhibitor system |
| HU196038B (en) * | 1987-08-07 | 1988-09-28 | Mta Koezponti Kemiai Kutato In | Process for producing antiherpetic pharmaceutics for external use, containing 5-isopropyl-2'-beta-deoxy-uridine |
| EP0326151B1 (en) * | 1988-01-29 | 1993-06-16 | Sumitomo Pharmaceuticals Company, Limited | Improved controlled release formulation |
| CA1339070C (en) * | 1989-01-26 | 1997-07-29 | Wulf Droge | Treatment of diseases associated with cysteine deficiency |
-
1996
- 1996-07-25 HU HU9602024A patent/HUP9602024A3/hu unknown
-
1997
- 1997-07-03 AT AT97929442T patent/ATE297752T1/de not_active IP Right Cessation
- 1997-07-03 CA CA002232710A patent/CA2232710A1/en not_active Abandoned
- 1997-07-03 DE DE69733539T patent/DE69733539D1/de not_active Expired - Fee Related
- 1997-07-03 WO PCT/HU1997/000035 patent/WO1998004280A2/en active IP Right Grant
- 1997-07-03 US US09/043,657 patent/US6048843A/en not_active Expired - Fee Related
- 1997-07-03 AU AU33549/97A patent/AU3354997A/en not_active Abandoned
- 1997-07-03 EP EP97929442A patent/EP0855915B1/en not_active Expired - Lifetime
- 1997-07-24 HR HRP9602024A patent/HRP970419A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP9602024A2 (hu) | 1998-03-30 |
| US6048843A (en) | 2000-04-11 |
| CA2232710A1 (en) | 1998-02-05 |
| HU9602024D0 (en) | 1996-09-30 |
| WO1998004280A3 (en) | 1998-03-26 |
| ATE297752T1 (de) | 2005-07-15 |
| EP0855915B1 (en) | 2005-06-15 |
| DE69733539D1 (de) | 2005-07-21 |
| HUP9602024A3 (en) | 1999-05-28 |
| WO1998004280A2 (en) | 1998-02-05 |
| AU3354997A (en) | 1998-02-20 |
| EP0855915A2 (en) | 1998-08-05 |
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