MD782Z - Method for vaccination against influenza - Google Patents
Method for vaccination against influenza Download PDFInfo
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- MD782Z MD782Z MDS20140008A MDS20140008A MD782Z MD 782 Z MD782 Z MD 782Z MD S20140008 A MDS20140008 A MD S20140008A MD S20140008 A MDS20140008 A MD S20140008A MD 782 Z MD782 Z MD 782Z
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- 206010022000 influenza Diseases 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title claims abstract description 10
- 238000002255 vaccination Methods 0.000 title claims description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 10
- 239000002775 capsule Substances 0.000 claims abstract description 9
- 229920002261 Corn starch Polymers 0.000 claims abstract description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 5
- 239000008120 corn starch Substances 0.000 claims abstract description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 5
- 235000012054 meals Nutrition 0.000 claims abstract description 4
- 229960003971 influenza vaccine Drugs 0.000 claims description 11
- 241000700605 Viruses Species 0.000 abstract description 5
- 229960005486 vaccine Drugs 0.000 abstract description 4
- 238000011321 prophylaxis Methods 0.000 abstract description 3
- 208000035473 Communicable disease Diseases 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 230000001681 protective effect Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 5
- 230000004957 immunoregulator effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000712461 unidentified influenza virus Species 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 2
- 102000005348 Neuraminidase Human genes 0.000 description 2
- 108010006232 Neuraminidase Proteins 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 230000027645 antigenic variation Effects 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 210000000852 deltoid muscle Anatomy 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000185 hemagglutinin Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 1
- 241000371980 Influenza B virus (B/Shanghai/361/2002) Species 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003312 immunocapture Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000037797 influenza A Diseases 0.000 description 1
- 208000037801 influenza A (H1N1) Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000003771 laboratory diagnosis Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 201000010740 swine influenza Diseases 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Invenţia se referă la medicină, în special la boli infecţioase şi poate fi utilizată pentru profilaxia gripei. The invention relates to medicine, in particular to infectious diseases and can be used for influenza prophylaxis.
Gripa este una dintre cele mai răspândite maladii pe glob, manifestându-se prin epidemii anuale în urma variaţiei antigenice minore (mutaţii punctiforme în genele care codifică hemaglutinina şi neuraminidaza) şi pandemii la un interval de 10…40 ani în urma variaţiei antigenice majore (apariţia de noi subtipuri de virusuri gripale cu hemaglutinină sau neuraminidază complet noi). Influenza is one of the most widespread diseases in the world, manifesting itself through annual epidemics following minor antigenic variation (point mutations in the genes encoding hemagglutinin and neuraminidase) and pandemics at intervals of 10…40 years following major antigenic variation (the emergence of new subtypes of influenza viruses with completely new hemagglutinin or neuraminidase).
Gripa reprezintă o problemă social-medicală la nivel mondial, manifestându-se prin epidemii anuale şi pandemii. Vaccinarea anuală a populaţiei împotriva gripei cu vaccin antigripal recomandat de OMS pentru sezonul viitor este cea mai eficientă modalitate de prevenire a îmbolnăvirilor de această maladie. Eficienţa vaccinării la diferite grupe de populaţie variază de la 58,0 până la 90,0% [1]. Influenza is a global social and medical problem, manifested by annual epidemics and pandemics. Annual vaccination of the population against influenza with the influenza vaccine recommended by WHO for the upcoming season is the most effective way to prevent the disease. Vaccination effectiveness in different population groups varies from 58.0 to 90.0% [1].
Vaccinarea anuală a populaţiei contra gripei reduce riscul de îmbolnăvire de la 58,0 până la 90,0%. Annual vaccination of the population against influenza reduces the risk of illness from 58.0 to 90.0%.
Dezavantajul metodei menţionate constă în aceea că o bună parte a populaţiei, de la 10,0 până la 42,0%, poate face gripă şi după vaccinare. The disadvantage of the mentioned method is that a large part of the population, from 10.0 to 42.0%, can get the flu even after vaccination.
Problema pe care o rezolvă prezenta invenţie constă în sporirea eficacităţii imunizării contra gripei. The problem solved by the present invention consists in increasing the effectiveness of immunization against influenza.
Conform invenţiei, metoda revendicată constă în aceea că se administrează vaccinul gripal şi concomitent se administrează un remediu ce include la o capsulă: (tomatozida-5α furostan-3α, 22,26triol-3[O-β-galactopiranozil(1→2)β-D-glucopiranozil(1→4)-β-D-galactopiranozid]-26-O-β-D glucopiranozid) - 0,05 g; celuloză microcristalină - 0,147 g; amidon de porumb - 0,100 g; stearat de magneziu - 0,003 g, câte o capsulă, cu 30 min înainte de masă, timp de 30 zile. According to the invention, the claimed method consists in administering the influenza vaccine and simultaneously administering a remedy that includes in one capsule: (tomatoside-5α furostane-3α, 22,26triol-3[O-β-galactopyranosyl(1→2)β-D-glucopyranosyl(1→4)-β-D-galactopyranoside]-26-O-β-D glucopyranoside) - 0.05 g; microcrystalline cellulose - 0.147 g; corn starch - 0.100 g; magnesium stearate - 0.003 g, one capsule each, 30 min before a meal, for 30 days.
Rezultatul tehnic constă în sporirea eficacienţei imunizării contra gripei datorită administrării vaccinului gripal şi a unui remediu ce include la o capsulă: (tomatozida-5α furostan-3α, 22,26triol-3[O-β-galactopiranozil(1→2)β-D-glucopiranozil(1→4)-β-D-galactopiranozid]-26-O-β-D glucopiranozid) - 0,05 g; celuloză microcristalină - 0,147 g; amidon de porumb - 0,100 g; stearat de magneziu - 0,003 g (Pacoverină). The technical result consists in increasing the effectiveness of immunization against influenza due to the administration of the influenza vaccine and a remedy that includes in one capsule: (tomatoside-5α furostane-3α, 22,26triol-3[O-β-galactopyranosyl(1→2)β-D-glucopyranosyl(1→4)-β-D-galactopyranoside]-26-O-β-D glucopyranoside) - 0.05 g; microcrystalline cellulose - 0.147 g; corn starch - 0.100 g; magnesium stearate - 0.003 g (Pacoverin).
Avantajele metodei revendicate constau în intesificarea procesului de imunogeneză la persoanele vaccinate contra gripei, exprimat prin creşterea numărului de persoane cu titru de anticorpi protectori (87,5…92,5%) şi a valorilor T-helper, unde raportul CD4/CD8 (Th/Ts) constituie 1,8%. The advantages of the claimed method consist in the intensification of the immunogenesis process in people vaccinated against influenza, expressed by the increase in the number of people with protective antibody titers (87.5…92.5%) and T-helper values, where the CD4/CD8 (Th/Ts) ratio is 1.8%.
Întru sporirea eficacităţii vaccinării contra unor infecţii se utilizează diferite produse medicamentoase de origine vegetală (MD 3120 G2 2006.08.31 şi MD 4177 C1 2013.02.28). La fel se cunoaşte şi utilizarea remediului medicamentos Pacoverină (MD 3120 G2 2006.08.31) pentru sporirea răspunsului imun cu un titru de anticorpi protectori > 100UI/l până la 92,1% faţă de 80,2% în lotul martor. In order to increase the effectiveness of vaccination against certain infections, various medicinal products of plant origin are used (MD 3120 G2 2006.08.31 and MD 4177 C1 2013.02.28). The use of the medicinal remedy Pacoverin (MD 3120 G2 2006.08.31) is also known to increase the immune response with a titer of protective antibodies > 100UI/l up to 92.1% compared to 80.2% in the control group.
În studiul dat sunt prezentate rezultatele aplicării remediului medicamentos Pacoverină în procesul de vaccinare contra gripei sezoniere. Studiul s-a efectuat pe un lot experimental (40 persoane - 18 bărbaţi şi 12 femei) şi lotul martor (40 persoane - 18 bărbaţi şi 12 femei) cu vârsta între 20 şi 30 ani. S-a utilizat vaccinul antigripal Vaxigrip (cu un conţinut de 15 µg de HA a tulpinilor virusurilor gripale A/California/7/2009 (H1N1)pdm09, A/Victoria/361/2011 (H3N2) şi B/Wisconsin/1/2010), produs de firma Sanofi Pasteur, Franţa, recomandat de OMS pentru sezonul 2012/2013 şi remediul medicamentos Pacoverină (tomatozida-5α furostan-3α, 22,26triol-3[O-β-galactopiranozil(1→2)β-D-glucopiranozil(1→4)-β-D-galactopiranozid]-26-O-β-D glucopiranozid) - 0,05 g; celuloză microcristalină - 0,147 g; amidon de porumb - 0,100 g; stearat de magneziu - 0,003 g), câte o capsulă de 50 mg, produs de Î .M. Farmaco S.A., Republica Moldova. This study presents the results of the application of the medicinal remedy Pacoverina in the process of vaccination against seasonal influenza. The study was conducted on an experimental group (40 people - 18 men and 12 women) and a control group (40 people - 18 men and 12 women) aged between 20 and 30 years. The influenza vaccine Vaxigrip (containing 15 µg of HA of the influenza virus strains A/California/7/2009 (H1N1)pdm09, A/Victoria/361/2011 (H3N2) and B/Wisconsin/1/2010), produced by Sanofi Pasteur, France, recommended by WHO for the 2012/2013 season, and the medicinal remedy Pacoverina (tomatoside-5α furostane-3α, 22,26triol-3[O-β-galactopyranosyl(1→2)β-D-glucopyranosyl(1→4)-β-D-galactopyranoside]-26-O-β-D glucopyranoside) - 0.05 g were used; microcrystalline cellulose - 0.147 g; corn starch - 0.100 g; magnesium stearate - 0.003 g), one capsule of 50 mg, produced by Î .M. Farmaco S.A., Republic of Moldova.
La persoanele din lotul experimental s-au administrat 0,5 ml de vaccin în muşchiul deltoid şi pe parcursul a 30 zile câte o capsulă de Pacoverină (50 mg) pe zi cu 30 min înainte de masă. La persoanele din lotul martor s-a administrat numai vaccinul Vaxigrip în muşchiul deltoid în doză de 0,5 ml. La persoanele din lotul experimental şi lotul martor până şi după vaccinare (peste 30 zile) a fost determinat titrul de anticorpi hemaglutinoinhibanţi în testul de hemaglutinoinhibare după metoda descrisă (Serogical diagnosis of influenza by haemaglutination inhibition testing. Manual for the laboratory diagnosis and virological surveillance of influenza. WHO Heat Organization 2011, p. 59-62) şi numărul celulelor cu proprietăţi imunoregulatoare (T-helper şi T-supresoare) prin testul Capcellia (Capcellia CD4/CD8 whole/sang total (quantitativ imunoassay for CD4 and CD8 T-limphocytes by immunocapture), BIO-RAD, France, 2000, 28p). The experimental group received 0.5 ml of vaccine in the deltoid muscle and one capsule of Pacoverin (50 mg) per day 30 minutes before meals for 30 days. The control group received only the Vaxigrip vaccine in the deltoid muscle in a dose of 0.5 ml. In the individuals from the experimental group and the control group before and after vaccination (over 30 days), the titer of hemagglutininhibitory antibodies was determined in the hemagglutininhibition test according to the described method (Serogical diagnosis of influenza by haemaglutination inhibition testing. Manual for the laboratory diagnosis and virological surveillance of influenza. WHO Heat Organization 2011, p. 59-62) and the number of cells with immunoregulatory properties (T-helper and T-suppressor) by the Capcellia test (Capcellia CD4/CD8 whole/total blood (quantitative immunoassay for CD4 and CD8 T-lymphocytes by immunocapture), BIO-RAD, France, 2000, 28p).
Rezultatele testării persoanelor din lotul experimental şi lotul martor la prezenţa anticorpilor hemaglutinoinhibanţi şi a numărului de celule imunoregulatoare (T-helper şi T- supresoare) sunt prezentate în tabelele 1 şi 2. The results of testing individuals from the experimental group and the control group for the presence of hemagglutininhibitory antibodies and the number of immunoregulatory cells (T-helper and T-suppressor) are presented in Tables 1 and 2.
Tabelul 1 Table 1
Titrul de anticorpi hemaglutinoinhibanţi în ser la persoanele din lotul experimental The titer of hemagglutininhibitory antibodies in serum in the experimental group
şi martor până la vaccinare and control until vaccination
Contingentele examinate Nr. de persoane Grupe de vârstă Antigenii virusurilor gripale A(H1N1)pdm A(H3N2) B < 1:40 ¤ < 1:40 < 1:40 Lot experimental 40 20…30 ani 40 40 40 Lot martor 40 20…30 ani 40 40 40Contingents examined No. of persons Age groups Influenza virus antigens A(H1N1)pdm A(H3N2) B < 1:40 ¤ < 1:40 < 1:40 Experimental group 40 20…30 years 40 40 40 Control group 40 20…30 years 40 40 40
Legendă : ¤ - titrul anticorpilor hemaglutinoinhibanţi în ser. Legend: ¤ - titer of hemagglutininhibitory antibodies in serum.
Conform standardelor internaţionale titrul protector de anticorpi hemaglutinoinhibanţi constituie ≥1:40. Astfel la iniţierea studiului persoanele din lotul experimental şi martor nu dispuneau de anticorpi protectori faţă de infecţia gripală. According to international standards, the protective titer of hemagglutininhibitory antibodies is ≥1:40. Thus, at the beginning of the study, the individuals in the experimental and control groups did not have protective antibodies against influenza infection.
Tabelul 2 Table 2
Rezultatele răspunsului imun la persoanele din lotul experimental şi martor până la vaccinare Results of the immune response in individuals from the experimental and control groups until vaccination
Contingentele examinate Nr. de persoane Grupa de vârstă T-limfocite Th CD4 Ts CD8 Th/Ts CD4/CD8 Lot experimental (persoanele până la vaccinarea contra gripei cu aplicarea Pacoverinei) 40 20…30 ani 785 ±272 530±231 1,5 Lot martor (persoanele până la vaccinarea numai cu vaccin antigripal) 40 20…30 ani 780±270 530±231 1,5Contingents examined No. of persons Age group T-lymphocytes Th CD4 Ts CD8 Th/Ts CD4/CD8 Experimental group (persons before vaccination against influenza with application of Pacoverin) 40 20…30 years 785 ±272 530±231 1.5 Control group (persons before vaccination with influenza vaccine only) 40 20…30 years 780±270 530±231 1.5
Numărul de celule imunoregulatoare (T-helper(CD4) şi T-supresoare(CD8)) şi raportul CD4/CD8 era în limitele caracteristice pentru această vârstă. Peste 30 zile de la imunizare persoanele din loturile experimental şi martor au fost din nou testate la prezenţa anticorpilor hemaglutinoinhibanţi şi a numărului de celule imunoregulatoare. Rezultatele sunt expuse în tabelele 3 şi 4. The number of immunoregulatory cells (T-helper (CD4) and T-suppressor (CD8)) and the CD4/CD8 ratio were within the limits characteristic for this age. After 30 days of immunization, individuals from the experimental and control groups were again tested for the presence of hemagglutininhibitory antibodies and the number of immunoregulatory cells. The results are presented in Tables 3 and 4.
Tabelul 3 Table 3
Rezultatele determinării titrului de anticorpi hemaglutinoinhibanţi contra gripei la persoanele din lotul experimental şi martor Results of determining the titer of hemagglutininhibitory antibodies against influenza in people from the experimental and control groups
Contingentele examinate Nr. de persoa- ne exami- nate Grupe de vârstă Antigenii virusurilor gripale A(H1N1)pdm A(H3N2) B <1:40 >1:40 <1:40 >1:40 <1:40 >1:40 Abs. % Abs. % Abs. % Abs. % Abs. % Abs. % Lot experimental (persoanele vaccinate contra gripei cu aplicarea Pacoverinei) 40 20…30 ani 3 7,5 37 92,5 4 10,0 36 90,0 5 12,5 35 87,5 Lot martor (persoanele vaccinate contra gripei numai cu vaccin) 40 20…30 ani 10 25,0 30 75,0 11 27,5 29 72,5 11 27,5 29 72,5Contingents examined No. of persons examined Age groups Influenza virus antigens A(H1N1)pdm A(H3N2) B <1:40 >1:40 <1:40 >1:40 <1:40 >1:40 Abs. % Abs. % Abs. % Abs. % Abs. % Abs. % Experimental group (people vaccinated against influenza with the application of Pacoverina) 40 20…30 years 3 7.5 37 92.5 4 10.0 36 90.0 5 12.5 35 87.5 Control group (people vaccinated against influenza with the vaccine only) 40 20…30 years 10 25.0 30 75.0 11 27.5 29 72.5 11 27.5 29 72.5
În lotul experimental la persoanele vaccinate contra gripei cu aplicarea Pacoverinei titrul de anticorpi protectori ≥ 1:40 a fost determinat la 37 (92,5%) persoane faţă de virusul gripal A(N1N1)pdm, la 36 (90,0%) - faţă de virusul A(H3N2) şi la 35 (87,5%) persoane faţă de virusul gripal de tip B, pe când în lotul martor titrul protector de anticorpi la 30 (75,0%) persoane faţă de virusul gripal A(H1N1)pdm, la 29 (72,5%) - faţă de virusul A(H3N2) şi la 29 (72,5%) persoane faţă de virusul gripal de tip B. Datele prezentate denotă că aplicarea Pacoverinei stimulează procesul de imunogeneză şi sporeşte numărul persoanelor cu titru protector de anticorpi faţă de infecţia gripală, date confirmate prin intervalul de încredere: valoarea p=0,05. In the experimental group of people vaccinated against influenza with the application of Pacoverin, the protective antibody titer ≥ 1:40 was determined in 37 (92.5%) people against the influenza A(N1N1)pdm virus, in 36 (90.0%) - against the A(H3N2) virus and in 35 (87.5%) people against the influenza type B virus, while in the control group the protective antibody titer was determined in 30 (75.0%) people against the influenza A(H1N1)pdm virus, in 29 (72.5%) - against the A(H3N2) virus and in 29 (72.5%) people against the influenza type B virus. The data presented show that the application of Pacoverin stimulates the immunogenesis process and increases the number of people with a protective antibody titer against influenza infection, data confirmed by the confidence interval: p value = 0.05.
Tabelul 4 Table 4
Rezultatele răspunsului imun la persoanele din lotul experimental şi martor Results of the immune response in people from the experimental and control groups
după vaccinare contra gripei cu şi în absenţa Pacoverinei after influenza vaccination with and without Pacoverin
Contingentele examinate Nr. de persoane Grupa de vârstă T-limfocite Th CD4 Ts CD8 Th/Ts CD4/CD8 Lot experimental (persoanele vaccinate contra gripei cu aplicarea Pacoverinei) 40 20…30 ani 963 ±272 535±231 1,8 Lot martor (persoanele vaccinate numai cu vaccin antigripal) 40 20…30 ani 853±270 533±231 1,6Contingents examined No. of persons Age group T-lymphocytes Th CD4 Ts CD8 Th/Ts CD4/CD8 Experimental group (people vaccinated against influenza with the application of Pacoverin) 40 20…30 years 963 ±272 535±231 1.8 Control group (people vaccinated only with influenza vaccine) 40 20…30 years 853±270 533±231 1.6
Menţionăm că numărul de celule limfocite T-helper s-a dovedit a fi mai mare în grupa persoanelor care concomitent cu vaccinul antigripal au primit Pacoverină. Valoarea T-helper a avansat în acest lot de la 785±272 la 963±272 celule x106/L. Valoarea markerului T-supresoare în ambele loturi pe parcursul studiului a rămas nemodificată. La finele studiului raportul CD4/CD8 a constituit 1,8 în lotul experimental faţă de 1,6 în lotul martor. We mention that the number of T-helper lymphocyte cells proved to be higher in the group of people who received Pacoverin concurrently with the flu vaccine. The T-helper value advanced in this group from 785±272 to 963±272 x106/L cells. The value of the T-suppressor marker in both groups during the study remained unchanged. At the end of the study, the CD4/CD8 ratio was 1.8 in the experimental group compared to 1.6 in the control group.
Tabelul 5 Table 5
Eficacitatea vaccinului gripal şi a vaccinului gripal cu aplicarea Pacoverinei în profilaxia gripei Efficacy of influenza vaccine and influenza vaccine with Pacoverin application in influenza prophylaxis
Vaccinul gripal Pacoverină Vaccinul gripal cu aplicarea Pacoverinei 72,5-75,0% * 74,0%^ 87,5-92,5%*Influenza vaccine Pacoverin Influenza vaccine with Pacoverin application 72.5-75.0% * 74.0%^ 87.5-92.5%*
* - ponderea persoanelor vaccinate contra gripei cu titru protector (>1:40) de anticorpi * - share of people vaccinated against influenza with a protective titer (>1:40) of antibodies
^ - indicele eficacităţii epidemiologice ^ - epidemiological effectiveness index
1. Alexandrescu V., Matei D., Sbâcea C. Ghid de diagnostic, tratament şi prevenire a gripei. Bucureşti, 2009, Editura Almatea, p. 59 1. Alexandrescu V., Matei D., Sbâcea C. Guide to diagnosis, treatment and prevention of influenza. Bucharest, 2009, Almatea Publishing House, p. 59
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| MDS20140008A MD782Z (en) | 2013-07-16 | 2013-07-16 | Method for vaccination against influenza |
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| MDS20140008A MD782Z (en) | 2013-07-16 | 2013-07-16 | Method for vaccination against influenza |
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| MD782Z true MD782Z (en) | 2015-01-31 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD3120G2 (en) * | 2005-09-15 | 2007-03-31 | Национальный Научно-Практический Центр Превентивной Медицины Министерства Здравоохранения Республики Молдова | Method of influenza prophylaxis |
| MD4177C1 (en) * | 2011-01-14 | 2013-02-28 | Национальный Центр Общественного Здоровья Министерства Здравоохранения Республики Молдова | Method for vaccination against hepatitis B of persons with immunodeficiency |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD3120G2 (en) * | 2005-09-15 | 2007-03-31 | Национальный Научно-Практический Центр Превентивной Медицины Министерства Здравоохранения Республики Молдова | Method of influenza prophylaxis |
| MD4177C1 (en) * | 2011-01-14 | 2013-02-28 | Национальный Центр Общественного Здоровья Министерства Здравоохранения Республики Молдова | Method for vaccination against hepatitis B of persons with immunodeficiency |
Non-Patent Citations (1)
| Title |
|---|
| Alexandrescu V., Matei D., Sbâcea C. Ghid de diagnostic, tratament şi prevenire a gripei. Bucureşti, 2009, Editura Almatea, p. 59 * |
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