CS209351B1 - Inactivated vaccination against infectious atrophic rinididis of pigs and method of manufacture of the same - Google Patents
Inactivated vaccination against infectious atrophic rinididis of pigs and method of manufacture of the same Download PDFInfo
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
látka proti infekčnej atrofickej rinitíde ošípanýchanti-infectious atrophic pig rhinitis
Vynález sa týká spósobu výroby inaktivovanej očkovacej látky proti infekčnej atrofickej rinitíde ošípaných z mikroorganizmu Bordetella bronchiseptica, ktorá má dobré imunizačné vlastnosti a ktoré možno použit na prevenciu infekčnej atrofickej rinitídy ošípaných. Vynález sa tiež týká aj samotnej očkovacej látky.The present invention relates to a method for the production of an inactivated vaccine against infectious atrophic rhinitis of Bordetella bronchiseptica, which has good immunizing properties and which can be used to prevent infectious atrophic rhinitis of pigs. The invention also relates to the vaccine itself.
Na prevenciu infekčnej atrofickej rinitídy ošípaných sa v súčasnosti používá perorálne álebó parenterálne pódávanie róznych antibiotik, sulfonamidov a iných farmakologíckých prípravkov. Na tomto základe boli u nás navrhnuté a v praxi použité niektoré metody terapie a prevencie infekčnej atrofickej rinitídy ošípaných.For the prevention of infectious atrophic rhinitis in pigs, oral oral parenteral administration of various antibiotics, sulfonamides and other pharmacological agents is currently used. On this basis, some methods of treatment and prevention of infectious atrophic rhinitis in pigs were proposed and used in practice.
Šrubař, B. (Veterinářství, 21: 234-236, 1971) podával asi 10 dní před pórodom prasniciam chlortetracyklín vo formě Aureovitu v dávkách 100 g na 100 kg žívej hmotnosti, spolu s 20 g sulfadimidínu. Štvrtý až piaty deň po zahájení perorálnej aplikácie liečiv sa prasniciam vypláchnu obidve nosné dutiny 1% vodným roztokom chlórtetracyklínu. Okrem toho sa aplikovali prasniciam intramuskulárne 2 g streptomycínu alebo oxymykoinu v dávke 20 až 25 ml. Po tomto ošetření sú prasnice premiestnené do vydezinfikovanej porodnice, kde sa pokračuje v podávaní chlórtetracyklínu. Miesto výplachov nosných dutin doporučuje podávať chlortetracyklín aerosolom po dobu asi hodiny denne za 4 dni. Doporučuje sa aplikovat' znovu antibiotiká před pórodom, alebo v priebehu porodu. Ciciakom sa podává 3. až 4. deň po narodení 3 ml Ferridextranu a vitamín A a D per os vo formě hydrosolu. Ciciaky sa odstavuj ú vo veku 3 až 4 týždňov. Pri podozrení výskytu infekčnej atrofickej rinitídy sa u ciciakov vykoná popísaná liečebná procedúra.Srubar, B. (Veterinary, 21: 234-236, 1971) administered chlortetracycline in the form of Aureovit at doses of 100 g per 100 kg bodyweight about 10 days prior to farrowing, along with 20 g of sulfadimidine. On days 4 to 5 after initiation of oral drug administration, both sinuses are rinsed with 1% aqueous chlorotetracycline solution. In addition, 2 g of streptomycin or oxymycoin were administered intramuscularly to the sows at a dose of 20 to 25 ml. After this treatment, the sows are transferred to a disinfected maternity hospital, where chlorotetracycline is continued. Instead of nasal lavage, it is recommended that chlortetracycline be administered by aerosol for about an hour per 4 days. It is recommended that antibiotics be re-administered before or during childbirth. Piglets are given 3-4 days after birth with 3 ml of Ferridextran and Vitamin A and D in the form of hydrosol. The piglets are weaned at 3 to 4 weeks of age. If infectious atrophic rhinitis is suspected, pigs should be treated as described.
Škaloud, J. a spol. (Veterinaria Spofa, 17: 69—92, 1975) sledovali účinnost’ preparátov Neomix (Spofa-tylosin + Sulfadimidin), Neomix (Spofa) v kombinácíi s tylanom pro inj. (Elanco), Spectamu (ABBOTT) a Galiimycín (ABBOTT) na výskyt a priebeh atrofickej rinitídy. Najlepšie sa osvědčil prípravok Neomix pri porovnaní s ostatnými v užitkových chovoch s nízkou zootechničkou úrovňou v tom smere, že viedol k výraznému zvýšeniu hmotnostných prírastkov, k zníženiu úhynu a čiastočnému zníženiu infekčnej atrofickej rinitídy. Autoři sa dcmnievajú, že uvedené preparáty s antibakteriálnymi účinkami nie sú schopné samé likvidovať infekčnú atrofickú rinitídu.Škaloud, J. et al. (Veterinaria Spofa, 17: 69-92, 1975) investigated the efficacy of Neomix (Spoftylosin + Sulfadimidine), Neomix (Spofa) in combination with Tylan for Inj. (Elanco), Spectam (ABBOTT) and Galiimycin (ABBOTT) for the appearance and course of atrophic rhinitis. Neomix has proven to work best in comparison with others in low-zootechnical livestock farms in that it has led to a significant increase in weight gain, a reduction in mortality and a partial reduction in infectious atrophic rhinitis. The authors conclude that said antibacterial agents are not capable of killing infectious atrophic rhinitis themselves.
V zahraničí Switzer, W. ř. (Vet. Med., 58: 571—574, 196Ξ») podával sulphamethazin v dávke 100 g na 1 t onu krmivá ošípaným, ktoré boli experimentálně iiifokovaně Bordetellou bronchisepticou. Liečivo bolo podávané 3 až 5 týždňov.Abroad Switzer, W. ř. (Vet. Med., 58: 571-574, 196Ξ ») administered sulphamethazine at a dose of 100 g per 1 tonne feed to pigs that were experimentally treated with Bordetella bronchiseptica. The drug was administered for 3 to 5 weeks.
S podstatné vyššími dávkami Sulphamethazinu,With substantially higher doses of Sulphamethazine,
100 až 500 g na 1 tonu krmivá po dobu 3 týždňov, zaznamenali výsledky (Akkermans, J. P. W. M. a spol., Tijdsch. Diergeneesk., 93:964—972, 1968).100 to 500 g per 1 ton of feed for 3 weeks, recorded the results (Akkermans, J. P. W. M. et al., Tijdsch. Diergeneesk., 93: 964-972, 1968).
Woods, G. T. a spol. (Canad. J. Comp. Med., 36: 49-54,1972) podávali počas 3 týždňov kombináciu antibakteriálnych látok v zložení 50 mg chlortetracyklínu, 50 mg sulphamethazinu a 25 mg prokain-penicilínu na 453,6 g krmivá. Dospěli k závěru, že uvedená zmes je efektívna v eradikácii zárodkov Bordetella bronchiseptica v nosnej dutině.Woods, G. T. et al. (Canad. J. Comp. Med., 36: 49-54, 1972) administered a combination of antibacterials of 50 mg chlortetracycline, 50 mg sulphamethazine and 25 mg procaine-penicillin per 453.6 g of feed for 3 weeks. They concluded that the mixture was effective in eradicating Bordetella bronchiseptica in the nasal cavity.
Po dlhodobom používaní uvedených liečiv sa objavujú rezistentně kmene mikroorganizmu Bordetella bronchiseptica. Harris, D. L. a Schwitzer, W. P. (Amer. J. Vet. Res., 30: 1161-1165,1969) pri vyšetřovaní zistili v 20 z 25 stád (80 %) výskyt rezistentných kmeňov Bordetella bronchiseptica k sulfonamidom. Okrem toho popísali Terakado, N. a spol. (Antimicrob. Ag. Chemoter., 3: 555 až 558, 1973) rezistentně kmene k sulfadiraetoxiou, streptomycínu a aminobenzylpenicilínu. Vznikli aj ďalšie problémy v súvislosti s podáváním spomínaných chemických prípravkov, ako je výskyt rezistentných kmeňov iných druhov mikroorganizmov v populácii ošípaných, výskyt nových infekcií a v neposlednom radě aj nutnost’ obmedzenia používania antibiotik z hradiska obecného zdravia.After prolonged use of these drugs, resistant strains of Bordetella bronchiseptica appear. Harris, D.L. and Schwitzer, W. P. (Amer. J. Vet. Res., 30: 1161-1165, 1969) investigated the occurrence of resistant Bordetella bronchiseptica strains to sulfonamides in 20 out of 25 herds (80%). In addition, Terakado, N. et al. (Antimicrob. Ag. Chemoter., 3: 555-558, 1973) resistant to sulfadiraethoxia, streptomycin, and aminobenzylpenicillin. Other problems have also arisen in connection with the administration of the above mentioned chemical preparations, such as the presence of resistant strains of other micro-organisms in the pig population, the emergence of new infections and, last but not least, the need to limit the use of antibiotics.
Kashiwazaki, M. a spol. (Nat. Inst. Anim. Health Quart., 12: 17—22, 1972); Koníček, J. a spol. (Vesmír, 51: 71 až 73, 1972); Rahkin, D. A. (JAVMA, 167: 274 až 278, 1975); Van Os, J. L. (Tijd. Diergennesk., 100: 999, 1975).Kashiwazaki, M. et al. (Nat. Inst. Anim. Health Quart., 12: 17-22, 1972); Koníček, J. et al. (Universe, 51: 71-73, 1972); Rahkin, D.A. (JAVMA, 167: 274-278, 1975); Van Os, JL (Tijd. Diergennesk., 100: 999, 1975).
Na základe uvedeného je v súčasnosti potřebné zaviesť vhodný biologický preparát na prevenciu infekčněj atrofickej rinitídy ošípaných.Accordingly, there is currently a need for a suitable biological preparation for the prevention of infectious atrophic rhinitis in pigs.
Podfa námi uvedených pokusov sa ukázalo, že je možné vyrobit inaktivovanú očkovaciu látku proti infekčnej atrofickej rinitíde z bakteriálněj kultúrý pripravenej submerzným spósobom kultiváde mikroorganizmu bordetella bronchiseptica v I. rastovej fáze. Mikroorganizmy v I. rastovej fáze obsahujú K antigén a. tento antigén je schopný vyvolať u myší ochranný účinok proti intracerebrálnej infekcii; vykazuje aglutináciusKantisérom; vyvolává nekrózu pri intrakutánnom injekčnom podaní morčatám; musia mať dobré hemaglutinačné vlastnosti (aglútinujú králičie erytrocyty do titra 1 : 32); vysokú kyslú aglutináciu (v Mclllvaneho pufre do hodnoty pH 4,2 až 4,6); v teste toxicity šupematant z bakteriálnych kultúr spósobuje úhyn niyší do riedenia 1 : 8 až 1 : 32 a v 10% roztoku NaOH mikroorganizmy lyzujú do 30 minút.Our experiments have shown that it is possible to produce an inactivated vaccine against infectious atrophic rhinitis from a bacterial culture prepared by a submerged method of culturing bordetella bronchiseptica in the first growth phase. Microorganisms in the I. growth phase contain the K antigen and. this antigen is capable of inducing a protective effect in mice against intracerebral infection; shows agglutination with Cantiser; induces necrosis by intracutaneous injection into guinea pigs; they must have good haemagglutination properties (aglutinate rabbit erythrocytes to a titer of 1:32); high acid agglutination (in Mcllvan buffer up to pH 4.2 to 4.6); in the toxicity test, the bacterial culture scavenger causes mortality lower to a dilution of 1: 8 to 1: 32 and in a 10% NaOH solution the microorganisms lysed within 30 minutes.
jPre výrobu inaktivovanej očkovacej látky podlá vynálezu sa používajú 4 kmene Bordetella bronchiseptica, ktoré splňajú uvedené rastové požiadavky. Kmene boli izolované autormi vynálezu od ošípaných v priebehu akútneho ochorenia infekčnej atrofickej rinitídy a sú uložené v „Československej sbírke mikroorganismů Univerzity J. E. Puruložené pod tyrruto čislami: Kultúra č.:For the production of the inactivated vaccine according to the invention, 4 strains of Bordetella bronchiseptica are used which satisfy the aforementioned growth requirements. The strains were isolated by the authors of the invention from pigs during an acute disease of infectious atrophic rhinitis and are deposited in the "Czechoslovak Collection of Microorganisms of the University of J. E. Puru, deposited under the following numbers: Culture no .:
Č-l = CCM 3304 P —5/2 = CCM 3305 DP-7 = CCM 3306 DP-5 = CCM 3307 kyně, Brno, tř. Obránců míru 10“. Kultury sú lokalita izolácie: Čergov Preselany Dolný Peter Dolný PeterČ-1 = CCM 3304 P — 5/2 = CCM 3305 DP-7 = CCM 3306 DP-5 = CCM 3307 Kyne, Brno, tř. Defenders of Peace 10 ”. The cultures are the isolation site: Cergov Preselany Dolny Peter Dolny Peter
Autoři vynálezu skúšali rózne druhy živných médií a rózne stimulátory rastu tak, aby mikroorganizmy obsiahnuté v bakteriálnej kultúre, z ktorej je vyrábaná inaktivovaná očkovacia látka, rástli v I. fáze. Bolo zistené, že kombinácia „Sojového živného média“, ktoré představuje roztok aminokyselin (proteínov) získaný enzymatickou hydrolýzou delipidizovanej sójovej múky, obsahujúceho 350 mg% celkového dusíka, 150 mg% aminodusíka a NaCl 0,4 g/100 ml. K tomuto produkčnému médiu sú přidané rastové stimulátory, ktorými sú 1% vodný roztok kvasničného extraktu (představuje vodný roztok čerstvých autolyzovaných kvasnic), 10% vodný roztok přípravku Bacto Casamino acids (firemný názov pre zmes aminokyselin získaný kyslou hydrolýzou kazeínu, obsahuje celkový dusík 10 %, NaCl 14^%, popol 15 %, fosfor ako kysličník fosforičitý 2 %) áalbumínová frakcia krvného séra alebo plazmy ošípaných v množstve 0,1 až 1,5 % (objemových), spíňatietó rastové požiadavky, že očkovacia látka vyrobená z mikroorganizmu Bordetella bronchiseptica, kultivovaného v uvedenej živnej póde, má dobrý preventivný účinok proti infekčnej atrofickej rinitíde ošípaných.The inventors tested different types of nutrient media and different growth promoters so that the microorganisms contained in the bacterial culture from which the inactivated vaccine is produced grow in phase I. It has been found that a combination of "Soy Nutrient Medium", which is an amino acid (protein) solution obtained by enzymatic hydrolysis of delipidized soy flour containing 350 mg% total nitrogen, 150 mg% amino nitrogen and NaCl 0.4 g / 100 ml. To this production medium are added growth stimulators which are 1% aqueous solution of yeast extract (representing an aqueous solution of fresh autolysed yeast), 10% aqueous solution of Bacto Casamino acids (the company name for a mixture of amino acids obtained by acid hydrolysis of casein, containing 10% total nitrogen) , NaCl 14 ^%, ash 15%, phosphorus as phosphorus pentoxide 2%) Albumin fraction of blood serum or plasma of pigs in an amount of 0.1 to 1.5% (v / v), has a growing demand that a vaccine made from Bordetella bronchiseptica cultivated in said nutrient broth has a good preventive effect against infectious atrophic rhinitis in pigs.
Podstatou vynálezu teda je inaktivovaná očkovacia látka proti infekčnej atrofickej rinitíde óšípaných, ktorá obsahuje v 1 ml 2 x IQ8 áž 20 x 108 , inaktivovaných zárodkov baktérií Bordetella bronchiseptica adsorbovaných na gel hydroxidu hlinitého, a to kmene baktérií CCM 5304, CCM 3305, CCM 3306, CCM 3307. 'The invention thus is an inactivated vaccine against infectious atrophic rhinitis in pigs comprising in 1 ml of 2 x IQ 8 to 20 x 10 8 inactivated germs of Bordetella bronchiseptica adsorbed to aluminum hydroxide gel, and the strains of CCM 5304, CCM 3305, CCM 3306, CCM 3307. '
Pre výrobu inaktivovanej očkovacej látky sa používajúbaktérie Bordetella bronchiseptica v I. rastovej fáze, ktoré sa kultivujú v sójovom živnom médiu, obhatenom o rastovo-stimulačné faktory, ktorými sú zmes aminokyselin, získaných kyslou , hydrolýzou kazeinu v množstve 0,5 až 1,5 hmotnostných %, kvasničný extrakt v množstve 0,05 až 0,15 hmotnostných %, albumínová frakcia z krvného séra alebo plazmy ošípaných v množstve 0,01 až 0,15 hmotnostných %, vztiahnuté na hmotnost živného média, pri teplote 36 až 37 °C, po dobu 20 až 36 hodin a potom sa získaná bakteriálna kultúra inaktivuje 4,8 až 5,2 % vodným roztokom formalínu v množstve 3,9 až 4,1 objemových % vztiahnuté na objem kultury, následné sa adsorbuje na gel hydroxidu hlinitého, ktorého množstvo je 30 až 35 objemových % vztiahnuté na objem kultury a po sedimentácii sa koncentruje odstránením supematantu.For the production of the inactivated vaccine, Bordetella bronchiseptica bacteria in the first growth phase are used, which are cultured in a soy nutrient medium enriched with growth-stimulating factors which are a mixture of amino acids obtained by acid hydrolysis of casein in an amount of 0.5 to 1.5% by weight. %, yeast extract in an amount of 0.05 to 0.15% by weight, an albumin fraction of blood serum or plasma of pigs in an amount of 0.01 to 0.15% by weight, based on the weight of the nutrient medium, at a temperature of 36 to 37 ° C, for a period of 20 to 36 hours and then the bacterial culture obtained is inactivated by a 4.8 to 5.2% aqueous formalin solution in an amount of 3.9 to 4.1% by volume based on the culture volume, then adsorbed onto an aluminum hydroxide gel whose amount is is 30 to 35% by volume based on the culture volume and is concentrated after removal of the supernatant after sedimentation.
Přínos tohto vynálezu spočívá v tom, že námi vyrobená očkovacia látka vytvoří u očkovaných ošípaných dobrú aktívnu imunitu proti infekčnej atrofickej rinitíde. Úplné alebo čiastočne odstráni používanie chemických prípravkov používaných na prevenciu tejto nákazy. Zníži náklady spojené s podáváním týcho prípravkov na prevenciu, a tým celkove zlepší ekonomiku chovu pri výrobě bravčového masa. Zníži sa množstvo používaných róznych širokospektrálnych antibiotik, čím sa zúžia možnosti výskytu prenosnej rezistencie.The benefit of the present invention is that the vaccine produced by us produces good active immunity against infectious atrophic rhinitis in vaccinated pigs. Completely or partially eliminates the use of chemical products used to prevent this disease. It will reduce the cost of administering these prevention products, thus improving the overall economy of the pigmeat sector. The number of different wide-spectrum antibiotics used will be reduced, thereby reducing the possibility of transmissible resistance.
, Vakcína je kontraindikovaná v chovoch, kde prebieha iné nákazlivé ochorenie prasiat a nesmie sa pódávať u prasnic menej ako 14 dní před pórodom.The vaccine is contraindicated in holdings where other contagious pig disease is present and must not be administered to sows less than 14 days prior to parturition.
Vakcína sa aplikuje podkožně do volného váziva prekolennej riasy, alebo pri kořeni ušného boltca.The vaccine is injected subcutaneously into the loose connective tissue of the kelp or at the root of the auricle.
Po aplikácii vakcíny nevznikajú žiadne reakcie.No reactions occur after vaccine administration.
Prasnice sa vakčinujú dvakrát v druhej polovici gravidity vždy s odstupom 14 dní, dávkami 10 ml. Druhá dávka musí byť podaná najneskór 14 dní před očakávaným pórodom. Prasiatka sa vakčinujú dvakrát a to vo veku 14 a 28 dní dávkou 3 ml.Sows are vaccinated twice in the second half of pregnancy at 14 days intervals, with doses of 10 ml. The second dose must be given at least 14 days before the expected birth. Pigs are vaccinated twice at 14 and 28 days of age with 3 ml.
Imunita nastupuje za 10 až 14 dní po poslednej dávke vakeíny. Imunně prasnice sú schopné kolostralnou cestou chránit svoje mláďatá proti infekcii dýchacích ciest zárodkami Bordetella bronchisepticá počas jedného pórodu. Vákcinované prasiatka sú schopné aktívnou tvorbou specifických protilátek chránit' sliznicu dýchacích ciest voči infekcii v období porodu.Immunity starts 10 to 14 days after the last dose of vaccine. Immune sows are able to protect their offspring against respiratory tract infection by Bordetella bronchisepticá in a single birth in a colostral way. Vaccinated piglets are able to protect the airway mucosa against infection during childbirth by actively producing specific antibodies.
Vakcína je vyhovujúca, ak priememý titer specifických aglutinačných protilátek dosahuje hodnotu 1 : 640. 7 The vaccine is satisfactory if the average titer of specific agglutinating antibodies is 1: 640. 7
Exspiračná doba vakcíny pri dodržaní skladovacích podmienok je 1 rok.The shelf life of the vaccine is 1 year, subject to storage conditions.
Příklad prevedeíiiáExample converts
K sterilnému „Sójovérnu živnému médiu“ sa za aseptických podmienok přidá 0,5 až 1,5 % (hmotnostných), optimálně 0,8 % hmotnostúých přípravku Bacte Casamifflo aúítfš, 0,05 až 0,15 % (hmotnostných) s optimorft 0,08 % přípravku Yeast extract a 0,01 až 0,15 htůoťnoštných % albumínovej frakcie. Do takto pripravefflej kultivačnej tekutej pódy sa naočkuje mikroorganizmus Bordetella bronchiseptica I. rastovej fázy. Kultivácia prebieha pri 36 až 37 °C ža stáfeho nuešania pri 170 ob/min. a přívode sterilného vzduchu 7 1/min. nepřetržíte počas celej kultivácie. pH je udržované na hodnotě 7,6. Pri poklese priepUstnosti na 50 % (meranej na Spekole proti referenčnej vzorke pri 575 nm) sa kultivácia ufeóíičí. Dížka kultivácie je 20 najdlhšíe 36 hodin. Po ukončení kultivácie sa bakferiáltia kultúra inaktivuje 5% vodným roztokom formalínu v pomere 4 % k objemu kultúry. Po 30 min. inaktivácii sa kultúra adsorbuje na Al(QH)3-gel v pomere 33 % k óBjěmu kultúry a naadsorbovaná kultúra sa nechá 48 hodin sedimentovať. Po sedimentácii sa inaktivovaná očkovacia látka zahustí na 1/3 póvodného objemu Odsátím supematantu a upraví sa akťúálffla acidita na hodnotu 5,8 až 6,8 pomocou hydrofosforečnanu sodného.0.5 to 1.5% (w / w), preferably 0.8% (w / w) of Bacte Casamifflo and at 0.05 to 0.15% (w / w) with an optimor of 0, are added to a sterile "soybean nutrient medium" under aseptic conditions. 08% Yeast extract and 0.01 to 0.15% of the albumin fraction. A Bordetella bronchiseptica I growth phase microorganism is inoculated into a culture liquid prepared in this way. Cultivation is carried out at 36-37 ° C after standing at 170 rpm. and a sterile air supply of 7 l / min. do not continue throughout the cultivation. The pH is maintained at 7.6. When the transmittance dropped to 50% (measured on the specimen against the reference sample at 575 nm), the culture was harvested. The length of cultivation is 20 for the longest 36 hours. After completion of the culture, the bacterial culture is inactivated with a 5% aqueous formalin solution in a ratio of 4% to the culture volume. After 30 min. by inactivation, the culture is adsorbed to Al (QH) 3- gel at a ratio of 33% to 6% of the culture and the adsorbed culture is allowed to settle for 48 hours. After sedimentation, the inactivated vaccine is concentrated to 1/3 of the original volume by aspiration of the supernatant and the acidity is adjusted to a value of 5.8 to 6.8 with sodium hydrogen phosphate.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS873877A CS209351B1 (en) | 1977-12-23 | 1977-12-23 | Inactivated vaccination against infectious atrophic rinididis of pigs and method of manufacture of the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS873877A CS209351B1 (en) | 1977-12-23 | 1977-12-23 | Inactivated vaccination against infectious atrophic rinididis of pigs and method of manufacture of the same |
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| Publication Number | Publication Date |
|---|---|
| CS209351B1 true CS209351B1 (en) | 1981-11-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS873877A CS209351B1 (en) | 1977-12-23 | 1977-12-23 | Inactivated vaccination against infectious atrophic rinididis of pigs and method of manufacture of the same |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS209351B1 (en) |
-
1977
- 1977-12-23 CS CS873877A patent/CS209351B1/en unknown
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