LT3127B - Antianemic preparation and process for preparing them - Google Patents

Abstract

Invention dealing with prophylaxis means for anaemia of sucking-pigs applies to the veterinary and chemistry fields. The proposed new anti-anaemic preparation is intended to maintain a optimal ionic amount in the blood of sucking-pigs and for anaemia prophylaxis of the same. The basis of the preparation consists of 1-phenyl-4-carboxy-2-pyrrolidinone sodium, iron, zinc, a mix of copper and cobalt salts. There are presented propositions regarding the production methods of various forms (suspension and powder) of the preparation.

Description

The present invention is in the veterinary and chemical field and can be used for the prevention of piglet mumps anemia. '-?

In piglets, the optimal amount of iron ions is required in the blood of piglets. The most common prophylaxis for anemia; containing • / containing potassium, sodium, magnesium, iron, copper; zinc, manganese, cobalt and chromium jbna / Ir aficarbinic and folic acid SU aut.l. No. 700131 v Japan Application No. 54-1777, which proposes v magnetic / intrinsic preparation y / containing active ingredient? Fe ^ G ^ ss small γ - / and ^; // * ':?.' -d // -Fe ₂ O ₃ . / in quantities ..: In the presence of this product: under the influence of animals

- 15 U in blood (/ increases, .. 'iron' and / calcium '*! Another GB formulation known from GB application' No. 1518364, containing acetylsalicylic '; / / acid' or l / its salts / mix? with '/'.g Iron/': / (11¾). · // / '/ -:' / '' - /: // ': dtuškal /// dame7' / used / y: ' 'acetylcellular: /' y acid ·:.;: '/-/2B'/.'///sodium, potassium, magnesium and / or aluminum salts, and ///' iron. '/'. , (III) .. /? Sulfate, i-gluconate, citrate, i / y-fumarate, lactate and carbonate.

4180567 is known and used in veterinary medicine an iron / y complex made from a high molecular weight pollutant oxyhydro - dixstrin, dextran, carboxyalkyl dextran, carboxyalkylcellulose / solutions of alginates and iron compounds / alkaline medium. / A stable solution is prepared at the base of this iron complex //? for injection. * Close to the present invention for antlanemic? - / ?;

the preparation has a water-soluble methionine-iron ¹ (III) complex / salt (U.S. Pat. No. 4,067,994). /;

/ Veterinary practice · piglet anemia // iron preparations used for prophylaxis: Ferodeks? / (Poland), Ferogliukin (CIS), Ferobalt (Japan,

Western Europe), Feroekt Impozil, Hemodeks, Rubrafer (Great Britain), Miofer, Urzaferon, Pigdeks {Germany), Ferumlek (Yugoslavia), Ferolim (IsraeliX isj>. Airedge / kt ^ ... Fedeks (Swedish ri. _F ''Per idekstr as, R .. Bernese / strof er {Bulgar Beraneis (Czech Republic, and

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i. / ao ^ Ke «« g, neKaeciBe »bix.ecA © i & aeaB ^« y c / x ^ 3ϊ ./-: ί® ^ «, © ../,: ί> 1 * R composition. enters, bivalent

When, / which.preparations. has feębaitOj, batting, zinc trace elements., / Usually · / .these,. preparations - / are in solutions, and.

bind /, gel-goose. ,, or. . .other /, of the specific- ..preparation

R containing metals., -Ions,. mostly .is / organic. origin-, · compound, and its-structure / is / commercial manufacturer; secret. '- of the present invention

/. - / '- ^: Analog R (prototype) yr - aatianemic. preparations. R Ferode-ks (Poland) and,, Ferogi kukin, <WS / countries). ,. 7- · R. '/

The above, 'anti-anemic,' .-. preparations,. widely used in veterinary practice, -. deficiency. that is, that they are into the body of animals, -. by injection / injection.

The first _r is, quite., Labor intensive, / procedure,. '' The second, '. piglets-juveniles during their '.. - during: experiencing - stress. ,/By the way.,

I.. ¹ lack of anti-anemic ,; preparations for ingestion. . -for animals, .su pas.a.EU. _r /asorfcimeBt.as. .and their efficiency: /

The present invention / object. // ~ - expand /, / anfcisneffiinis, .preparations and. increase.' .preparation ... efficiency

This .frequency / ./available in the anti-anemic .preparation using / iron · <II> in copper :,. .-A mixture of zinc, cobalt 'and 1-phenyl' 4 'carb'Oksl- ^: 2 - p £ r-Ql.idinone · salts :. water.

in the form of suspension or dry powder, the anti-anemic preparation is prepared from 1-phenyl-4-ka: boxoxy -2-pyrrolidinone sodium ion exchange solution

7 or by mixing the sodium salt of l-phenyl-4-carboxy-2-pyrrolidinone with inorganic salts of iron, copper, zinc or cobalt. Since l-phenyl-4-carboxy-2 '· pyrrolodinone is a water-insoluble compound, the ion exchange reaction can only be carried out in solution, so that' 1 / phenyl * 4 'carboxy-2-pyridylidene / / is dissolved in sodium hydroxide solution 7, //, / o- after 7: it / adds a calculated amount of the appropriate iron, copper, zinc '/ 7 or cobalt / salts7 / / Aqueous / slurry / antianemic preparation requires / large containers, in addition / difficulties in storing it / at low temperatures.

To avoid the above-mentioned problems, the same antianemic preparation is also proposed as a dry powder. In this case, l-phenyl-4-carboxy-2-pyrrolidinone sodium and the corresponding / metals / inorganic compounds are prepared. / ^ in the form of a dry powder.

'to /../ X' / ^ 7- ^ 7 ^ /// 7 '//.

The invention is illustrated by the following examples.

i- Example 1.

Preparation of 301.1.1-F-phenyl-4-carboxy-2-pyrrolidinone sodium salt solution. 205.2 g (1 mol) of 1-phenyl-4-carboxy-2-pyrrolidinone are dissolved in 200 ml of a 17% (5.05 mol) solution of sodium hydroxide.

T.2. Preparation of Iron (II) Salt of l-Phenyl-4-carboxy-2-pyrrolidinone. To 182 ml of a solution of 1-phenyl-4-carboxy-2-pyrrolidinone sodium salt,

' ⁴ '; made under 1, under vigorous stirring, add a solution of 278 g of iron (II) sulphate, dissolved in 500 ml of water (2.0 mol), and stir ^; another 20 min

'' + .. ++ {7; / '+

1.3. i'-Fenxi 4-Carboxy: Preparation of 2-Pyrrolidinone 'Copper Salt Suspension. To 35 mL of 1-phenyl, -4-carboxy-2-. pyrrolidine sodium salt solution prepared according to

1.1, /. stirring, pouring in 43, 8> g of copper sulphate dissolved; A solution of 79 mL of water (2.22 mol) was added and stirred for a further 3-0 min. .

1.4. Phenyl 4-carboxy-2-pyrrolidinone cobalt salt suspension (preparation. To 3.6 ml of l-phenyl-4-carboxy-215 'pyrrolidinone sodium salt solution prepared according to

1.1, add a solution of 4.72 g of cobalt acetate in 8.5 ml of water (2.23 mol) with stirring and stir for 10 min.

1.5. Preparation of the suspension of l-Fe _T nyl-4-carboxy-2-pyrrolidinone zinc / suspension. To 120 ml of a solution of l-phenyl ~ 4-caffboxoxy-2-pyrrolidinone sodium salt prepared according to

1.1, under vigorous stirring, add a solution of 175.5 g of zinc sulphate dissolved in 316 ml of water (1.93 / mol) and stir for a further 20 minutes.

1.6. Preparation of the anti-anemic preparation in aqueous suspension. To a suspension of iron (II) salt of l-phenyl-4L-carboxy-2-pyrrolidinone (prepared according to

1.2), gradually stirring l-phenyl-4-carboxy- /

2-Pyrrolidinone copper salt suspension (prepared according to 1.3), 1-phenyl-4-carboxy-2-pyrrolidinone cobalt salt suspension (prepared according to 1.4j and 1-phenyl-4-carboxy2-pyrrolidinone zinc salt suspension (prepared according to.

1.5), stirred for 10 min. This produces a greenish suspension of 1 ml containing: 0,0399 g Fe, 0,008 g Cu,

0.0008 g Co and 0.0285 g Zn.

. Example 2. /. 2.1. /: Preparation of l-Phenyl-4 ~ carboxy ~ 2 ”pyrrolidine © / ./hatri-7, 7 (powder · ^; :). /? In a rotary evaporator, evaporate the 1-phenyl-4-carboxy-2-pyridine solution (sodium salt, prepared). 1.1.

2.2. Antianendhio <7''preparation07: ' ^: 'ęavifes77'išiitėiid'; / pąyifelų7'.7i · Fine crushed (or ground) 278 g' (1 mol) .0 iron (II) sulfate FeSCh.7H ₂ O); 43.7 g (0.175 mol) of CuSO / copper sulfate. 5H ₂ O; 7,7g / (0.0189 / mol) / cobalt;

acetate (CH ₃ COO) ₂ Co. 4H ₂ O and 287.5 g (1 mol) of zinc sulphate / 'ZnSO ₄ .FH <^. / The resulting / mixture / thoroughly mixed' with 500 g (2; 2 mol) of dry l-phenyl-4 ' / 5 Sodium salts of carboxy-2-pyrrolidinone. 1 g of the preparation dry powder contains: 0, 0501 g Fe, 0.0099 g Cu, 0, .0010 g Co and 0.0587 g Zn.

Antianaemic (suspensijosj effect of iron? 0 absorption in the body of animals is illustrated by the data presented below. 1.5 months. Old piglets through z // ds'_/;:introduces'<then / ^<. </ Ml '· preparation / / It. / dose / selected / / based on / / preliminary results <. results, //. count- / / j on 7 /. by / z, how much -: piglet / will receive // // iron, ///./ /.

> 5 depending on its weight. Blood / haematological tests // data 'are given in Table / 1. From the / presented data 7, it appears that / after the administration of the proposed product // iron / // resorption takes place after one hour 7. which / '7'iailgil / Decreases by run, but after 24 hours · iron / piglets 7) 0 found more in body than at start of test / free / 7 / / transferrin / blood / serum changed adequately / / / 7, the level of transferrin at the start of the test was 785.71 and 83, 88 mmol / i respectively. The decrease in TB / serum i5 7 / serum exposure is due to the increased involvement of the protein in iron transport.

Effect of antianemic preparation (suspension) on iron absorption for 1.5 months. Table for age piglets

t Gel- hello, arole / 1 Lazy - five trans- ferines, mmol.l Protein, 'r g%. Charm reserve, mg% 4 »wrist / preparation - introduction .. 23.77 83.88 7.51 506 after entering 'preparation, ^ © · 1 hour ..' /: 41.18 78.73 7.15 515 h; . Prepared preparations . Or. ' 34.65 76, 92 7, 32 593 6 hours after administration. 22.91 80.45 6.46 505 After administration of the product, after 12 ... 19.40 88.28 6.78 620 After administration, p © 24 or. 27.18 85.71 6.96 -

Effect of antianemic preparation (suspension) on morphological and biochemical parameters of sows' blood.

. «Table

Morphological and biohexeftical indicators of blood

Ti- Pre- Fe mg% Hb g% very thromatic heme- special Hb scary para- rocky -boci- 'tokri tro- .machine. moji to  * · this, this. that * would go special group language little, ml million / m ³ thousands 3 mm . % volume tro- cite i · 10th 254.92 10.8 5.28 3.86 32.6 0.578 3,863 . 2 z 16th 274.92 10.3 5.96 3.93 32.0 0, -523 3,218 .'3 '/ , 20 35o, 56 12.0 4.03 4.43 40.0 0.987 .3,024 4 con- tro- funds 304.91 10.0 2/49 2, 90 40.0 ' 0.606 2,975

The effect of the antianemic preparation on the morphological and biochemical parameters of 'sow blood' 5 is shown in Table 2. For sows 10-14 days (group 1) and 3 days (group 2) before farrowing and 14 days (group 3) after sowing, the appropriate amount of the product is ingested. A maximum of 10 iron, hemoglobin, and platelets were observed in sows fed with 20 ml of the proposed antianeminib preparation (Study Group 3).

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Table i shows the effect of the proposed anti-anemic (suspension) formulation on morphological and biochemical parameters of piglets at 2 weeks of age after oral administration to sows. From. .delivered-.data shows .how effect / hemoglobin .indices, blood more. erythrocytes, .7 protein in 7 platelets, and ./ iron. ? . In piglet-rat blood / pigs fed 16 ml of the proposed preparation 7, iron 7 was 14%. More, /: compared to '10 'control group 7 in which sows did not receive this preparation. , than in piglets / gilts

7 · '· after. birth / was? Ferro-GlucinS injection (prototype). Similar data were obtained from comparative field trials. ^: conditions, using. miscellaneous. ?

7 antianemic preparations: proposed 7 (suspension) and, prototypes, Ferodex and Feroglucin, which are injected into piglets (Table 4).

Effects of preparation (suspension and dry powder) on morphological indices in piglets-piglets after oral administration to sows .5 '·' · Table '. ? '' 7 '' t. . -.

- You ~ Par- t Par- Prepara- Fe Hb ' Bal- Different scary sheepskin j · Selonian 'know- to . preparation .. mmol.l measles g% , tto- 'no- ifl O j X gru language ^; blisters form this, Fri small language min / min gru-. small mm / foot ⁽ 0 ? 3 ' 5 suspension 17.67 8.6 4.16 .4.32 3 ', 5 * « 23.68 7.2 5/25 3.49 1 ' '3 5 M 16.83 8.6 5.25 3, 97 3 5. . W 22.01 8.2 5.25 4.14.

. 3 .. .// 73 / 7-7 · / +5 ' 7'5- · 7; 7 '-n ·' n 24.37 15.25 8.8 8.8 3.03 5, 25 3.6.2 average: 19.96 +8., + 36. 5.18 '3,928 ·  3; 7 5 / dry. - powder 27.42 11 * 0 5.25 ' 3.48 '»' ³ ++ // / 7 + 5 +: // 15,, 99 '.'8,2 .. 5.03 5.18 2 /7+3.'.-7 / ..7'5 · / + / 27/42 7 Τ, ϊ ·· 5 _r 03 • - - 7-3. + /: ';' .. '· / ⁵ . ' «· - · I7> 06 7.2 5.25 ' 3.76 / + / 3 77 ' 7 + 5 · ' 17/67 ./9.7. 5.25 3.31 7 + 3 + 77 · '. + .- / 57 / '® ^: ·., - 18.43. 11.0 5.25 4.04 - .., .. + .7 / - // vįefc <kis / + : /20.66. 9.0 5,176 3,954

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5 '' / shapes /.../(suspension· /.or or/: 'dry / powder), · /. by oral administration. preparation + / sows; / with: /; feed, / + EirmoS / studied: groups. sows + -70-14 +, days /. against / sows. 3 / 'and + 10-14 / ·.'. + - / days .po // /pat$ayi^si/+;buyd.'/ _? + sxFuck; +> o / _? / l, 2: // & l // preparation /; | sUppensis its /:p.ayidąlel,,//+Antros; / + groups under investigation /'.// , _; : pigs / 10,, / for babies · / in / same / days / dumbbell- ^: after: - .. 10 g / preparation '· ///.?;/// iaausus' / meal./ .) /! · '.-... // / Above/////submit..../ ./ / data + /. , _; , rodp, +. / +. that. // offered. , · Patented £ /: antianeminia ../ preparataš /., Promoted by: / iron re15. zorbci her; in the body., +, +. positively /:./ acting / not only. sows .- +++ <where £ oms ./; with +. / feed // s »fed / preparation.tas ·) ,, / blood, morpho •: log'inius ,, i7 + .bioccbeminiUs ::, / ^ pointer.uS +,. / - .. ^; but // and / piglets-. Blood Glucose Indicators. According to some / indicators, the patented + antimicrobial is superior to the currently used / veterinary preparations / Feroglycine and Ferodex; The latter preparations are injected into the preparation. piglets-to-piglets are offered a patented preparation for sows with feed,

Claims (5)

DEFINITION OF INVENTION An antianemic preparation, a mixture of various inorganic salts and an organic compound, characterized in that: 5 in that it comprises the sodium salt of 1-phenyl-4-carboxy-2-pyrididinone in the following ratio, by weight. %:. 1 '·. 1-Phenyl-4-carboxy-2-pyrrolidinone · 44.0 · · - 44.5 Sodium · · / 7 Iron Sulfate / FeSO ₄ .7H ₂ O / 25.6 - 26.0 Zinc Sulfate / ZnSO ^ .IHjO/ '25.5 - 26.0 Copper sulfate / CuSO ₄ .5H ₂ O / 3.8 to 4.0 Cobalt acetate / C0 {CH3COO) 2.4H ₂ O / j 0 / 63-0.65 A process for the preparation of the antianeemic preparation of claim 1 further comprising dissolving l-phenyl-4-carboxy-2-pyrrolidinone in sodium hydroxide solution b formed by l-phenyl-4-carboxy-2-pyrrole / dinone liberates sodium salt, in dry form and afterwards 15 mixed with 7 corresponding amounts of the dry salts of iron sulfate, copper sulfate, zinc sulfate and cobalt acetate to obtain an antianmic preparation in solid form. 20 3. The anti-anemic agent of claim 1 for preventing prophylaxis in piglet mice by adding this agent to a sow feed.