DK153739B

DK153739B - Preparation for rehydrating monogastric animals and humans which/who are suffering from diarrhoea

Info

Publication number: DK153739B
Application number: DK198385A
Authority: DK
Inventors: Mogens Gjerloev
Original assignee: Mogens Gjerloev
Priority date: 1983-10-03
Filing date: 1985-05-02
Publication date: 1988-08-29
Also published as: DK153739C; DK198385A; DK198385D0

Description

iin

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Opfindelsen angår et præparat til rehydrering af monogastriske dyr og mennesker, der lider af diarré, hvilket præparat indeholder et vandbindende kvælde-middel, elektrolytter og en sukkerart. Diarréen er 5 især ikke-infektiøs diarré og diarré forårsaget af rota- og coronavirus.The invention relates to a composition for the rehydration of monogastric animals and people suffering from diarrhea, which composition contains a water-binding swelling agent, electrolytes and a sugar. Diarrhea is 5 especially non-infectious diarrhea and diarrhea caused by rota and coronavirus.

Dødeligheden blandt nyfødte dyr, såsom kalve og grise, inden for landbrugserhvervet er selv i velorgani-10 serede landbrugslande med god dyrlægedækning stadig meget stor. F.eks. blev der i Danmark i 1980 destrueret omkring 180.000 kalve, hvilket svarer til næsten 20% af de kalve, der fødes hvert år. Årsagen til en del af kalvedødeligheden og også til en del af til-15 svarende dødsfald blandt pattegrise er, at de bliver stressede, når de vænnes fra og anbringes f.eks. i fællesfolde. Når dyrene tages fra og således ikke mere får modermælk, udvikler helt op til halvdelen af dyrene diarré, fordi de får stress på grund af f.eks.The mortality of newborn animals, such as calves and pigs, in the agricultural industry is still very high even in well-organized agricultural countries with good veterinary coverage. Eg. In Denmark around 180,000 calves were destroyed in 1980, which corresponds to almost 20% of the calves born each year. The reason for some of the calf mortality and also some of the corresponding deaths among piglets is that they become stressed when they are weaned and placed e.g. in joint folds. When the animals are taken away and thus no longer receive breast milk, up to half of the animals develop diarrhea because they are stressed by, for example.

20 foderskift og transport. Man antager, at halvdelen af dødsfaldene skyldes diarré opstået inden for den første måned efter fødslen. En del kalve lider også af rota- og coronavirusinfektion, der er en smitsom tarminfektion, hvor køer er virusbærere og smitter kal-25 vene. Sygdommen skyldes bl. a. stærkt nedsat produktion af lactase, således at dyrene ikke kan spalte lactose i den mælk, de fodres med, og herefter udvikles der hurtigt diarré ved osmotisk effekt i tarmkanalen.20 feed change and transport. It is believed that half of the deaths are due to diarrhea occurring within the first month after birth. Some calves also suffer from rota and coronavirus infection, which is an infectious intestinal infection where cows are virus carriers and infect the calves. The disease is caused by a. greatly reduced production of lactase, so that animals cannot cleave lactose in the milk with which they are fed, and then diarrhea rapidly develops by osmotic effect in the intestinal tract.

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Nyfødte kalve og grise med diarré vil tabe betydeligt i vægt på grund af dehydrering, og mange dør.Newborn calves and pigs with diarrhea will lose significant weight due to dehydration and many die.

I DE fremlæggelsesskrift nr. 2.455.281 er der omhand-In DE Publication No. 2,455,281,

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2 let et middel til rehydratisering af husdyr, hvilket middel består af elektrolytter i form af nærmere angivne salte og glycin samt af glucose. Det i dette DE fremlæggelsesskrift omhandlede illustrerer blot, at 5 et middel med den angivne sammensætning modvirker diarré.2 readily a means for rehydrating livestock, which consists of electrolytes in the form of specified salts and glycine as well as glucose. The disclosure referred to in this DE merely illustrates that an agent of the stated composition counteracts diarrhea.

I DK patentansøgning nr. 551/81 er der omhandlet et middel til at reducere stresstilstande og reducere 10 forekomsten af diarré hos monogastriske dyr, hvilket middel ifølge kravene er baseret på en Plantago-art, medens der i det eneste udførelseseksempel i beskrivelsen til denne DK patentansøgning alene er illustreret et middel bestående udelukkende af Ispaghula 15 Husk. Det bemærkes herved, at det på side 4, linie 14-17 i beskrivelsen til denne patentansøgning om det deri omhandlede middel er angivet, at dets egenskaber ikke ændres ved tilsætning af NaCl eller KC1, selv i nærværelse af citronsyre (hvilket er væsent-20 ligt ved behandling af svære diarréer, hvor der gives kaliumioner). Denne angivelse ses at være et udtryk for, at det efter den pågældende ansøgers opfattelse alene er Ispaghula Husk, der modvirker diarré hos monogastriske dyr, hvilket ses at være helt på linie 25 med det, der gives udtryk for ved det i nævnte eneste udførelseseksempel illustrerede.DK Patent Application No. 551/81 discloses a means of reducing stress states and reducing the incidence of diarrhea in monogastric animals, which agent is based on a Plantago species, whereas in the only embodiment of the description of this DK patent application alone is illustrated a remedy consisting solely of Ispaghula 15 Husk. It is hereby noted that on page 4, lines 14-17 of the description of this patent application for the agent disclosed therein, it is stated that its properties are not altered by the addition of NaCl or KCl, even in the presence of citric acid (which is essentially 20%). similar to the treatment of severe diarrhea where potassium ions are given). This indication is seen as an indication that, in the applicant's view, it is Ispaghula Husk alone who counteracts diarrhea in monogastric animals, which is seen to be completely in line with what is illustrated in the only exemplary embodiment illustrated in the said embodiment. .

Fra DE offentliggørelsesskrift nr. 2.644.197 kendes der et middel til bekæmpelse af diarré hos monoga-30 striske dyr og nyfødte drøvtyggere, hvilket middel i det væsentlige består af et materiale, der i det mindste i et vist omfang fungerer som et vandbindende kvældemiddel, nemlig forgelatineret stivelse, af elektrolytter samt en sukkerart, der sammen med 3DE Publication No. 2,644,197 discloses a remedy for diarrhea in monogastric animals and newborn ruminants, which essentially consists of a material which at least to some extent acts as a water-binding swelling agent. namely, pregelatinized starch, by electrolytes as well as a sugar containing 3

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andre sukkerarter er indeholdt i bestanddelene cere-lose og tørmælk, som angivet på side 9 i tabel II.other sugars are contained in the constituents cerelos and dry milk, as listed on page 9 of Table II.

Formålet med opfindelsen er at angive et præparat til 5 behandling af diarré, således at en meget stor del af de syge dyr kan kureres i løbet af ganske få dage, hvorved dødsfald på grund af væsketab undgås.The object of the invention is to provide a composition for the treatment of diarrhea, so that a very large proportion of the sick animals can be cured within a few days, thereby avoiding deaths due to fluid loss.

Dette opnås ved at sammensætte præparatet som angivet 10 i krav l’s kendetegnende del. Det har overraskende vist sig, at en blanding af det vandbindende kvælde-middel Ispaghula Husk, der er tørrede frøskaller af Plantago ovata, en eller flere elektrolytter, glucose og ét eller flere lactosespaltende enzymer er et hur-15 tigt og effektivt middel mod diarré uden påviselige bivirkninger, og med bedre effekt end med de enkelte bestanddele alene. Præparatet kan anvendes til behandling af diarré hos alt afkom af drøvtyggere, så længe disse er énmavede, dvs. før de er begyndt at 20 tygge drøv, samt til behandling af ikke-infektiøs diarré og diarré forårsaget af rota- og coronavirus hos alle andre énmavede dyr og mennesker. Det lactosespaltende enzym spalter den lactose, som f.eks. en kalv under en diarré ikke selv er i stand til at 25 spalte og fordøje. Uspaltet lactose i tarmkanalen er med til at forværre en diarré. Ved visse andre behandlingsmetoder har man foreslået at spalte lacto-sen i mælken, inden kalvene får mælken, men med præparatet ifølge opfindelsen spaltes lactosen først i 30 kalvens mave og tarm, hvilket giver færre bivirk ninger, f.eks. i form af spisevægring.This is accomplished by assembling the composition as set out in Claim 1 of the characterizing portion. Surprisingly, it has been found that a mixture of the water-binding swelling agent Ispaghula Husk, which is dried seed shells of Plantago ovata, one or more electrolytes, glucose and one or more lactose-splitting enzymes is a fast and effective agent for diarrhea without detectable side effects, and with better effect than with the individual ingredients alone. The preparation can be used to treat diarrhea in all offspring of ruminants as long as they are mono-gastric, ie. before they have started chewing rum, as well as for the treatment of non-infectious diarrhea and diarrhea caused by rota and coronavirus in all other one-tailed animals and humans. The lactose cleaving enzyme cleaves the lactose which e.g. a calf during a diarrhea is not even able to split and digest. Undigested lactose in the intestinal tract aggravates a diarrhea. In certain other treatment methods, it has been proposed to cleave the lactose in the milk before the calves receive the milk, but with the composition according to the invention the lactose is first cleaved in the stomach and intestine of the calf, causing fewer side effects, e.g. in the form of eating refusals.

I betragtning af, at præparatet ifølge opfindelsen ud over elektrolytter og glucose indeholder såvel detConsidering that the composition of the invention, in addition to electrolytes and glucose, contains both

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4 vandbindende kvældemiddel Ispaghula Husk som en eller flere lactaser, adskiller præparatet ifølge opfindelsen sig fra det fra nævnte DE fremlæggelsesskrift nr. 2.455.281 kendte middel, idet præparatet ifølge op-5 findelsen i kraft af tilstedeværelsen af det vandbindende kvældemiddel Ispaghula Husk samt én eller flere lactaser danner en gel, hvis egenskaber er angivet i en fortegnelse nedenfor under pkt. a) til f), hvilket det kendte middel som følge af sin sammensætning ikke 10 er i stand til.4 water-binding swelling agent Ispaghula Remember as one or more lactases, the composition according to the invention differs from the agent known from said disclosure no. 2,455,281, the composition according to the invention by virtue of the presence of the water-binding swelling agent Ispaghula Husk and one or more several lactases form a gel, the properties of which are listed in the list below under clause. a) to f), which the known agent is not capable of due to its composition.

Over for det fra nævnte DK patentansøgning nr. 551/81 kendte middel står præparatet ifølge opfindelsen, der ud over Ispaghula Husk skal - ikke kan - indeholde 15 elektrolytter og tillige skal indeholde såvel glucose som én eller flere lactaser. Den forskel mellem egenskaberne hos præparatet ifølge opfindelsen og egenskaberne hos det fra denne DK patentansøgning kendte middel, der er betinget af den obligatoriske forskel 20 i de to materialers kvalitative sammensætning, medfører, at præparatet ifølge opfindelsen adskiller sig fra det fra denne DK patentansøgning kendte middel.Opposite to the agent known from said patent application No. 551/81 stands the composition according to the invention, which in addition to Ispaghula Husk must - cannot - contain 15 electrolytes and must also contain both glucose and one or more lactases. The difference between the properties of the composition according to the invention and the properties of the agent known from this DK patent application, which is conditional on the compulsory difference 20 in the qualitative composition of the two materials, means that the composition according to the invention differs from the agent known from this DK patent application. .

Den mulige forskel i kvalitativ sammensætning mellem de to materialer kan ikke formindske, men vil kun 25 kunne forøge forskellen mellem egenskaberne hos de to materialer, hvilken forøgelse bevirker, at de to materialer adskiller sig i endnu højere grad.The possible difference in qualitative composition between the two materials cannot be reduced, but will only be able to increase the difference between the properties of the two materials, which increases the difference between the two materials to an even greater extent.

I forhold til det fra nævnte DE offentliggørelses-30 skrift nr. 2.644.197 kendte middel adskiller præparatet ifølge opfindelsen sig i henseende til sammensætning på to væsentlige punkter:In relation to the agent known from the aforementioned DE Publication No. 2,644,197, the composition according to the invention differs in terms of composition in two essential respects:

Det første punkt er, at det vandbindende kvældemiddel 5The first point is that the water-binding swelling agent 5

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i præparatet ifølge opfindelsen, nemlig Ispaghula Husk, er et ikke fordøjeligt materiale, hvilket indebærer, at det ikke bliver nedbrudt under dets passage af mavetarmkanalen, i modsætning til det vandbindende 5 kvældemiddel i det fra dette DE offentliggørelsesskrift kendte middel, nemlig forgelatineret stivelse, der er et fordøjeligt materiale, hvilket indebærer, at det bliver nedbrudt under dets passage af mavetarmkanalen. En helt afgørende konsekvens af denne 10 forskel er, at, medens præparatet ifølge opfindelsen danner en gel i tarmkanalen som angivet nedenfor i nærværende beskrivelse, vil det kendte middel ikke, eller muligvis kun i meget ringe omfang, være i stand til at danne en gel i tarmkanalen, hvilket nødvendig-15 vis vil bevirke en forskel i egenskaberne ved brugen i praksis af præparatet ifølge opfindelsen og det kendte middel, jfr. det nedenfor anførte vedrørende den konstaterbare forskel i egenskaberne ved brugen i praksis af disse materialer.in the composition according to the invention, namely Ispaghula Husk, is a non-digestible material, which means that it is not degraded during its passage through the gastrointestinal tract, in contrast to the water-binding swelling agent of the agent known from this DE publication, namely pregelatinized starch, which is a digestible material, which means that it is degraded during its passage through the gastrointestinal tract. A crucial consequence of this difference is that, while the composition of the invention forms a gel in the intestinal tract as set forth below in this specification, the known agent will not, or possibly only to a very small extent, be capable of forming a gel. in the intestinal tract, which will necessarily cause a difference in the properties of the use in practice of the composition of the invention and the known agent, cf. as stated below regarding the noticeable difference in the properties of the use in practice of these materials.

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Det andet punkt er, at præparatet ifølge opfindelsen indeholder én eller flere lactaser til nedbrydning af forekommende lactose, medens det fra dette DE offentliggørelsesskrift kendte middel ikke indeholder en 25 eller flere lactaser. Hertil kommer, at forekommende lactose vil forværre en diarré, når den ikke bringes ud af billedet, f.eks. ved nedbrydning med lactase. 1The second point is that the composition of the invention contains one or more lactases for degradation of occurring lactose, while the agent known from this DE publication does not contain a 25 or more lactases. In addition, occurring lactose will aggravate a diarrhea when not brought out of the picture, e.g. by degradation with lactase. 1

Den konstaterbare forskel i egenskaberne ved brugen i praksis af præparatet ifølge opfindelsen og det fra dette DE offentliggørelsesskrift kendte middel, til hvilken forskel der er henvist i næstforegående afsnit, består i, at, medens præparatet ifølge opfin-The noticeable difference in the properties of the use in practice of the composition according to the invention and the means known from this DE publication, to which difference referred to in the preceding paragraph, consists in that, while the composition according to the invention

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6 delsen først indgives efter konstateret diarré som angivet nedenfor i nærværende beskrivelse, indgives det kendte middel inden konstateret diarré som angivet i offentliggørelsesskriftet, tabel IV med tilhø-5 rende tekst, specielt fodnote 1) til denne tabel.If the report is first filed after ascertained diarrhea as set forth below in this specification, the known agent prior to ascertained diarrhea as set forth in the disclosure document, Table IV with accompanying text, especially footnote 1) is submitted to this table.

Det her anførte vedrørende forskellene i sammmensæt-ningen og egenskaberne mellem præparatet ifølge opfindelsen og det fra dette DE offentliggørelsesskrift 10 kendte middel indebærer, at præparatet ifølge opfindelsen adskiller sig fra det fra dette DE offentliggørelsesskrift kendte middel.As stated herein regarding the differences in composition and properties between the composition of the invention and the agent known from this DE publication 10, the composition of the invention differs from the agent known from this DE publication.

Præparatet ifølge opfindelsen fremstilles ganske sim-15 pelt ved, at de enkelte dele afvejes og blandes, således at det færdige præparat leveres som et tørt pulver klart til brug.The composition of the invention is prepared quite simply by weighing and mixing the individual parts so that the finished composition is delivered as a dry powder ready for use.

En anden stor fordel ved præparatet ifølge opfindel-20 sen er, at man kan kurere dyr for diarré uden anvendelse af særlige antibiotika, således at man undgår ulemperne herved i form af medicinrester i dyret og mulighederne for at udvikle antibiotikaresistente bakteriestammer.Another great advantage of the composition according to the invention is that one can cure animals for diarrhea without the use of special antibiotics, thus avoiding the disadvantages of drug residues in the animal and the possibility of developing antibiotic resistant bacterial strains.

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Det er en speciel fordel, at de vandbindende plantefibre i i kvældemidlet Ispaghula Husk kvælder op i tarmen på en meget velegnet og naturlig måde, som giver tarmindholdet en geleagtig konsistens, således at 30 afføringen vil have normal konsistens allerede et par timer efter første fodring med præparatet. Jo hurtigere en diarré hos en kalv eller en pattegris bringes under kontrol, jo større er chancen for, at dyret vil . overleve. Indholdet af glucose samt de nødvendige 7It is a special advantage that the water-binding plant fibers in the swelling agent Ispaghula Remember to swell up the intestine in a very suitable and natural way, which gives the intestinal contents a gel-like consistency, so that the stool will have normal consistency already a few hours after the first feeding of the preparation. . The sooner a diarrhea in a calf or piglet is brought under control, the greater the chance that the animal will. stay alive. The content of glucose and the necessary 7

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salte i rette mængder fremmer næringsoptagelsen og giver det svækkede dyr en let omsættelig energi.Salts in right amounts promote nutrient uptake and give the weakened animal an easily marketable energy.

Det er ifølge opfindelsen meget hensigtsmæssigt, at 5 elektrolytterne i præparatet omfatter sådanne salte, som erstatter salte tabt ved diarré, idet man ved re-hydrering så blot behøver at indgive ét præparat, der bevirker både rehydrering eller stop for dehydrering og tilfører de tabte salte og den tabte væske.According to the invention, it is very convenient that the electrolytes in the composition comprise such salts which replace salts lost by diarrhea, when in rehydration one simply has to administer one preparation which causes both rehydration or stop dehydration and feeds the lost salts. and the lost fluid.

10 Når præparatet som omhandlet i krav 3 omfatter en buffer, kan man undlade at beskytte enzymerne ved særlige foranstaltninger, idet præparatet selv i en periode på op til 6 timer stabiliserer mavens pH-vær-15 di, så enzymerne ikke inaktiveres, og man behøver ikke i tarmen at afvente f.eks. opløsning af et overtræk, men enzymet er straks klart til at udøve sin funktion. Herved spares også beskyttelsesforanstaltninger for enzymet.When the composition of claim 3 comprises a buffer, the enzymes can be protected by special measures, the preparation itself stabilizing the gastric pH for a period of up to 6 hours so that the enzymes are not inactivated and not waiting in the gut e.g. solution of a coating, but the enzyme is immediately ready to perform its function. This also saves protective measures for the enzyme.

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De indgående bestanddele skal være sådanne, der er farmaceutisk tolerable, og en kombination af de i krav 4 angivne bestanddele gør det muligt at opnå den foreliggende opfindelses formål.The constituent constituents are those which are pharmaceutically tolerable and a combination of the constituents of claim 4 makes it possible to achieve the object of the present invention.

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Ved at sammensætte præparatet som omhandlet i krav 5 fås et simpelt præparat, der har de nødvendige egenskaber, dvs. virker stoppende på diarré, tilfører de nødvendige salte, tilfører lactase og bringer dette 30 upåvirket gennem maven på en simpel måde.By forming the composition as claimed in claim 5, a simple composition having the necessary properties, i.e. stops diarrhea, feeds the necessary salts, feeds lactase and brings it unaffected through the stomach in a simple way.

Forholdet mellem de enkelte komponenter i præparatet ifølge opfindelsen kan variere meget, men det har vist sig, at man får en optimal virkning og beskyt-The ratio of the individual components of the composition according to the invention may vary widely, but it has been found that an optimal effect and protective effect is obtained.

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8 telse af enzymet, hvis de enkelte komponenter anvendes i de forhold, som er nærmere angivet i krav 6. Anvender man dette præparat øjelikkeligt, når man konstaterer symptomer på diarré hos et dyr, og er der 5 tale om såkaldte problembesætninger, bør præparatet ifølge opfindelsen anvendes, blot dyret vægrer sig ved at drikke op, og en diarré kan normalt standses blot ved at behandle dyret få gange. Man får således øjeblikkeligt standset det livstruende tab af vand og 10 salte (elektrolytter), således at langt de fleste af de angrebne dyr overlever og restitueres hurtigere end, hvis de kun behandledes med elektrolytter alene eller de vandlindrende fibre alene. Den hurtigere restituering af dyrene bevirker derfor en bedre til-15 vækst, hvilket er bevist med kliniske forsøg.If the individual components are used in the conditions specified in claim 6. If this composition is used immediately when symptoms of diarrhea are found in an animal and in case of so-called problem herds, the composition according to the invention is used only if the animal refuses to drink and a diarrhea can usually be stopped simply by treating the animal a few times. Thus, the life-threatening loss of water and 10 salts (electrolytes) are immediately halted, so that the vast majority of affected animals survive and recover faster than if treated with electrolytes alone or the water-relieving fibers alone. The faster recovery of the animals therefore results in better growth, as demonstrated by clinical trials.

Ved at sammensætte præparatet som angivet i krav 7 fås et præparat, der standser diarré hos dyr og bevirker rehydrering, idet præparatet blot skal oprøres 20 i vand eller mælk eller en vand-mælk blanding, hvorefter et dyr villigt drikker dette.By forming the composition as claimed in claim 7, a composition is obtained which stops diarrhea in animals and causes rehydration, the preparation only having to be stirred up in water or milk or a water-milk mixture, after which an animal willingly drinks it.

Ved brug til mennesker sammensættes præparatet uden fyldstof og farvestoffer, men med smagskorrigerende 25 stoffer med den i krav 8 angivne sammensætning, idet en sammensætning som angivet i krav 9 især foretrækkes, da et sådant præparat er effektivt og samtidig har en tiltalende smag. 1For use in humans, the composition is composed without filler and colorants, but with flavor-correcting substances with the composition of claim 8, with a composition as claimed in claim 9 being particularly preferred, since such a composition is effective and at the same time has an appealing taste. 1

Man anvender præparatet ifølge opfindelsen ved at i-hælde 40-55 g af blandingen i lunkent vand, mælk eller en vand-mælk blanding ved omkring 38°C. Man får herved en blanding, som dyrene meget villigt drikker, . og som kurerer dem for diarré, fordi den gel, somThe composition of the invention is used by pouring 40-55 g of the mixture into lukewarm water, milk or a water-milk mixture at about 38 ° C. You get a mixture that the animals drink very willingly. and which cures them for diarrhea because the gel that

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9 præparatet danner i tarmkanalen, har følgende egenskaber: a) en beskyttende virkning på selve tarmslim- 5 hinden, b) binder nogle af bakterierne og deres toksiner til sig, 10 c) sikrer en normal tarmpassage (peristaltik), d) standser hurtigt tabet af væske og elektrolytter, 15 e) bufferkapaciteten hidrørende fra de tilsatte elektrolytter i den dannede gel beskytter den tilsatte lactase mod inaktivering i op til 6 timer, og 20 f) lactasen spalter den i tarmen værende lacto se og genskaber således normal osmotisk balance.9 the preparation forms in the intestinal tract, has the following properties: a) a protective effect on the intestinal mucosa itself, b) binds some of the bacteria and their toxins, 10 c) ensures a normal intestinal passage (peristalsis), d) stops the loss quickly e) the buffer capacity resulting from the added electrolytes in the gel formed protects the added lactase from inactivation for up to 6 hours, and f) the lactase cleaves the intestinal lactose and thus restores normal osmotic balance.

Til brug for mennesker opnås de samme resultater som 25 ovenfor, idet der til præparatet om ønsket kan anvendes en kold væske. 1For human use, the same results as above are obtained, as a cold liquid can be used for the preparation if desired. 1

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Praktisk forsøg med præparatet ifølge opfindelsen 480 spædkalve, alle to til tre uger gamle, blev ind-5 taget til opdrætningsforsøg under ensartede optimale forhold med hensyn til hygiejne, klima og fodring for at afprøve præparatets effekt over for diætetisk diarré hos spædkalve.Practical experiment with the composition of the invention 480 infant calves, every two to three weeks old, were taken for breeding experiments under uniform optimal conditions with regard to hygiene, climate and feeding to test the effect of the preparation against dietary diarrhea in infant calves.

10 Ved første fodring, efter at de indtagne kalve var anbragt i forsøgsstationens stald, fik alle kalvene hver tre liter af en konventionel elektrolyt/vand blanding, hvorefter man gik gradvis i løbet af fem dage op til 7 liter mælkeerstatning. Kalvene havde 15 iøvrigt fri adgang til hø og almindeligt tilskudsfoder.10 At first feeding, after the ingested calves were placed in the test station's barn, all the calves were each given three liters of a conventional electrolyte / water mixture, after which they gradually went up to 7 liters of milk for five days. The calves also had 15 free access to hay and regular supplementary feed.

I løbet af fjorten dage fra indsætningen fik 86 af kalvene, altså 17,9%, mave/tarmforstyrrrelser. Disse 20 dyr blev straks behandlet med præparatet ifølge opfindelsen.Within fourteen days of insertion, 86 of the calves, ie 17.9%, had stomach / intestinal disorders. These 20 animals were immediately treated with the composition of the invention.

73 af de syge kalve, altså 89,4%, blev helt helbredt i løbet af få dage. De 13 kalve, der ikke straks blev 25 helbredt ved behandlingen, fik herefter supplerende behandling med antibiotika.73 of the sick calves, 89.4%, were completely healed within a few days. The 13 calves that were not immediately cured during treatment were then given additional antibiotic treatment.

Det ses heraf, at den diarré, som mange sødmælkskalve og pattegrise får tidligt, ofte skyldes virusinfek-30 tioner samt transportstress, stress fra foderskift og stress fra miljøskift m.v. og kan derfor kureres med præparatet ifølge opfindelsen uden anvendelse af antibiotika. Kun 13 dyr ud af 86, altså ca. 15%, krævede supplerende antibiotisk behandling.It can be seen from this that the diarrhea that many calf milk calves and piglets get early is often due to viral infections as well as transport stress, stress from feed change and stress from environmental change etc. and can therefore be cured with the composition of the invention without the use of antibiotics. Only 13 animals out of 86, ie approx. 15%, required additional antibiotic treatment.

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Behandlingsforløb ved anvendelse af præparatetTreatment course using the preparation

Præparatet opblandes i vand og doseres efter dyrets 5 vægt, idet man anvender mængder ifølge følgende skema:The composition is mixed in water and dosed according to the weight of the animal, using amounts according to the following scheme:

Dyrets vægt Dosis_pr._fodring Fodr. pr. døgn 10 ca. 20 kg 0,5 1 vand + ca. 25 g 4 ca. 30 kg 1 1 " + ca. 50 g 4 ca. 40 kg 1,5 1 " + ca. 75 g 3-4 ca. 50 kg 2 1 " + ca. 100 g 3 15 ca. 60 kg 2,5 1 " + ca. 125 g 3Animal weight Dose_pr._ feeding Feeding per. day 10 approx. 20 kg 0.5 l water + approx. 25 g 4 approx. 30 kg 1 1 "+ about 50 g 4 approx. 40 kg 1.5 1" + approx. 75 g 3-4 approx. 50 kg 2 1 "+ about 100 g 3 15 approx 60 kg 2.5 1" + approx. 125 g 3

Efter det første døgn kan man med fordel tilsætte 25-50 g surmælksprodukt, såsom f.eks. syrnet mælk, 20 yoghurt eller ymer, pr. liter. Gradvis fra tredjedagen går man over til den normale foderblanding.After the first day, it is advantageous to add 25-50 g of sour milk product, such as e.g. soured milk, 20 yogurt or yeast, per liter. Gradually from the third day you switch to the normal feed mix.

Der findes også besætninger, hvor mave/tarmforstyr-relser er et tilbagevendende problem. Her kan man med 25 fordel give f.eks. kalve præparatet ifølge opfindelsen, lige så snart de blot vægrer sig ved at drikke op af det normale foder, f.eks. bestående af sødmælk eller andre mælkeblandinger. 1There are also herds where gastrointestinal disorders are a recurring problem. Here one can advantageously give e.g. calves the composition of the invention as soon as they simply wean themselves off drinking from the normal feed, e.g. consisting of whole milk or other milk mixtures. 1

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12 S ammenligningsforsøg12 S equation trials

De kurative egenskaber mod diarré af præparatet iføl-5 ge opfindelsen blev ved et kontrolleret forsøg sammenlignet med egenskaberne af Calmix neo ved en hollandsk kalveopfedningsstation. Calmix neo består af kaliumphosphat, natriumcitrat, natriumchlorid, natri-umhydrogencarbonat, citronsyre, glucose og neomycin.The curative properties against diarrhea of the composition of the invention were compared in a controlled experiment with the properties of Calmix neo at a Dutch calf fattening station. Calmix neo consists of potassium phosphate, sodium citrate, sodium chloride, sodium bicarbonate, citric acid, glucose and neomycin.

1010

Til forsøgene blev der brugt ialt 230 kalve, som blev inddelt i 5 grupper af 46 dyr. De blev anbragt i træbåse med ristegulv, hvor der var sørget for ventilation. Der anvendes en uge gamle kalve. Dyrene blev 15 vejet før forsøgene, efter 29 dage og efter 58 dage.A total of 230 calves were used for the experiments, which were divided into 5 groups of 46 animals. They were placed in wooden booths with rice floors where ventilation was provided. One week old calves are used. The animals were weighed before the experiments, after 29 days and after 58 days.

Ved starten gives som førstefodring 1,5 1 vand og 75 g elektrolyt. Foderet bestod af en pose Heftica pr. kalv efterfulgt af Hemeka start og opfedning ifølge det sædvanlig skema. Heftica er et kunstigt mælkepul-20 ver, der består af råt protein, råt fedt, rå fibre, aske, vitaminerne A, d3 og E samt spiramycinbase-kob-ber ud fra kobbersulfat, pentahydrat. Hemeka start er også et kunstigt mælkepulver, der består af råt protein, råt fedt, rå fibre, aske, vitaminerne A, D3 og 25 E samt spiramycinbase.At first, 1.5 liters of water and 75 g of electrolyte are given as the first feeding. The feed consisted of one bag of Heftica per day. calf followed by Hemeka start and fattening according to the usual schedule. Heftica is an artificial milk powder consisting of raw protein, raw fat, raw fiber, ash, vitamins A, d3 and E as well as spiramycin base copper from copper sulfate, pentahydrate. Hemeka start is also an artificial milk powder consisting of raw protein, raw fat, raw fiber, ash, vitamins A, D3 and 25 E as well as spiramycin base.

Ved diarré gives enten præparatet ifølge opfindelsen eller Calmix neo. 1In diarrhea, either the composition according to the invention or Calmix neo is given. 1

De opnåede forsøgresultater er anført i nedenstående tabel.The test results obtained are listed in the table below.

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Gennemsnitsresultater Konservativ Præparat kurativ behandling behandling ifølge op- (Calmix neo) findelsen 5Average results Conservative Preparative curative treatment treatment according to the (Calmix neo) finding 5

Antal kalve 15 15Number of calves 15 15

Gennemsnitsvægt ved start 41,6 kg 38,3 kg efter 29 dage 47,5 kg 45,3 kg 10 " 58 dage 74,4 kg 73,7 kgAverage weight at start 41.6 kg 38.3 kg after 29 days 47.5 kg 45.3 kg 10 "58 days 74.4 kg 73.7 kg

Gennemsnitsvækst efter 29 dage 5,9 kg 7,0 kg " 58 dage 32,8 kg 35,4 kg 15Average growth after 29 days 5.9 kg 7.0 kg "58 days 32.8 kg 35.4 kg 15

Gennemsnitsvækst indtil 29 dage 5,9 kg 7,0 kg 29-58 dage 26,9 kg 28,4 kg 20 Gennemsnitsvækst/dag efter 29 dage 203 g 241 g " 58 dage 565 g 610 g 1 2 3 4 5 6Average growth up to 29 days 5.9 kg 7.0 kg 29-58 days 26.9 kg 28.4 kg 20 Average growth / day after 29 days 203 g 241 g "58 days 565 g 610 g 1 2 3 4 5 6

De kurative egenskaber hos præparatet viser sig at 2 være gode. Kalvene viste efter 58 dage i gennemsnit 3 2,6 kg større vækst end kontrolgruppen, som blev be 4 handlet med Calmix neo. Ydermere steg den gennemsnit 5 lige vækst pr. dag hos de dyr, der blev behandlet med 6 præparatet ifølge opfindelsen, i den anden periode mere end hos de dyr, der blev behandlet med Calmix neo. Dette viser, at ikke alene påvirkes absorptionen og tarmens fordøjelseskapacitet mindre, men samtidig genvindes de hurtigere. Dette resultat støtter, at 14The curative properties of the composition are found to be good. After 58 days, the calves showed an average of 2.6 kg greater growth than the control group, which was treated 4 with Calmix neo. Furthermore, the average 5 equal growth per per day in the animals treated with the 6 composition of the invention in the second period more than in the animals treated with Calmix neo. This shows that not only is the absorption and digestive capacity of the intestine less affected, but at the same time they are recovered faster. This result supports that 14

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farmakokinetikken for præparatet ifølge opfindelsen bygger på en beskyttelse af tarmvæggen mod patogene angreb koblet sammen med en opretning af lactaseman-gel ved hjælp af syrebestandig lactase, hvorved både 5 sekretet og den osmotiske komponent bekæmpes.The pharmacokinetics of the composition according to the invention are based on the protection of the intestinal wall against pathogenic attacks coupled with a rectification of lactase gel by acid-resistant lactase, thereby fighting both the secretion and the osmotic component.

Eksempel 1Example 1

Præparatet ifølge opfindelsen kan f.eks. have følgen-10 de sammensætning: 1.000 g indeholder:The composition of the invention may e.g. have the following composition: 1,000 g contains:

Magnesii oxydum 5,75 g elek- 15 Citronsyre 13,50 gMagnesii oxydum 5.75 g of citric acid 13.50 g

Kaliumchlorid 24,00 g tro-Potassium chloride 24.00 g

Natriumcitrat 26,50 gSodium citrate 26.50 g

Natriumchlorid 41,50 g lyt-Sodium Chloride 41.50 g

Natriumhydrogencarbonat 68,00 g ter 20Sodium bicarbonate 68.00 g ter 20

Glucose 350,00 g sukkerartGlucose 350.00 g sugar

Terra rubrum 2,50 g farvestof 25 Hvedeklid 68,00 g fyldstofTerra rubrum 2.50 g dye 25 Wheat bran 68.00 g filler

Ispaghula Husk (tørrede frøskaller af Plantago ovata) 400,00 g vandbindende 30 fibreIspaghula Remember (dried seed husks of Plantago ovata) 400.00 g of water-binding 30 fibers

Lactase 0,25 g enzymLactase 0.25 g enzyme

Ialt 1.000,00 gTotal 1,000.00 g

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De enkelte bestanddele, der alle forefindes som tørt pulver, blandes maskinelt og er herefter straks klar til brug.The individual ingredients, all available as dry powder, are mixed mechanically and are then immediately ready for use.

5 Præparatet ifølge opfindelsen må ikke indgives på tør form, men skal suspenderes i f.eks. vand og indgives som en opløsning eller suspension. Kvældningen sker herefter i tarmkanalen over et passende tidsrum, hvorved det ved væskeabsorption kvælder op og giver 10 tarmindholdet en passende konsistens og binder og medtager nogle af bakterierne og deres toksiner, således at en diarré straks stoppes.The composition of the invention may not be administered in dry form, but must be suspended in e.g. water and administered as a solution or suspension. The swelling is then carried out in the intestinal tract for a suitable period of time, whereby by liquid absorption it swells up and gives the intestinal contents an appropriate consistency and binds and includes some of the bacteria and their toxins so that a diarrhea is immediately stopped.

Eksempel 2 15Example 2 15

Præparatet ifølge opfindelsen kan også have følgende sammensætning, som især foretrækkes til human brug; 1.000 g indeholder: 20The composition of the invention may also have the following composition, which is particularly preferred for human use; 1,000 g contains: 20

Magnesii oxydum 6,17 gMagnesii oxydum 6.17 g

Citronsyre 14,50 gCitric acid 14.50 g

Kaliumchlorid 25,75 gPotassium chloride 25.75 g

Natriumcitrat 28,45 g 25 Natriumchlorid 44,56 gSodium citrate 28.45 g Sodium chloride 44.56 g

Natriumhydrogencarbonat 73,00 gSodium bicarbonate 73.00 g

Glucose 375,80 g 30 Ispaghula Husk, formalet 429,50 gGlucose 375.80 g 30 Ispaghula Remember, ground 429.50 g

Lactase 0,27 gLactase 0.27 g

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Perbermynteolie 2,00 gPeruvian mint oil 2.00 g

Ialt 1,000,00 g 5Total 1,000.00 g 5

Eksempel 3Example 3

En suspension eller opløsning af det i eksempel 1 fremstillede præparat fremstilles ved at blande 50 g 10 præparat til 1 liter vand. pH-værdien i det friskfremstillede præparat er 8,56. Ved titrering til en pH-værdi på 5,73 anvendes 40,5 mækv. saltsyre, hvilket viser, at der er en ikke ubetydelig buffervirkning i præparatet, som vil "neutralisere" saltsyren i 15 ventriklen og dermed beskytte lactasen.A suspension or solution of the composition of Example 1 is prepared by mixing 50 g of 10 composition with 1 liter of water. The pH of the freshly prepared preparation is 8.56. When titrated to a pH of 5.73, 40.5 meq. hydrochloric acid, which shows that there is a not insignificant buffering effect in the preparation which will "neutralize" the hydrochloric acid in the ventricle and thus protect the lactase.

De i eksemplerne anvendte kemikalier er almindelige handelskemikalier, og lactasen er fortrinsvis CHBS lactase 25.000 fra Chr. Hansens Laboratorium, Køben-20 havn.The chemicals used in the examples are common commercial chemicals, and the lactase is preferably CHBS lactase 25,000 from Chr. Hansens Laboratory, Copenhagen-20 port.

25 125 1

Claims

1. Preparation for rehydration of monogastric animals and 5 people suffering from diarrhea, containing a water-binding swelling agent, electrolytes and a sugar, characterized in that it consists of Ispaghula Remember as the water-binding swelling agent, of electrolytes, of glucose, and of one or 10 or more lactases, and optionally also containing one or more fillers, one or more flavor-correcting substances and / or one or more dyes.

Composition according to claim 1, characterized in that the electrolytes comprise such salts which replace salts lost by diarrhea.

Composition according to claim 1 or 2, characterized in that the electrolytes are composed to give a buffer effect in the composition when dissolved or suspended.

Composition according to claim 1, 2 or 3, characterized in that the electrolytes are a mixture of two or more of the compounds magnesium oxide, magnesium carbonate hydroxide, magnesium hydroxide, magnesium silicate, calcium silicate, calcium carbonate, alkali metal chlorides such as sodium or potassium chloride, 30 alkali metal hydrogen carbonates such as sodium or potassium hydrogen carbonate, aluminum phosphate, aluminum hydroxide, citric acid or alkali metal citrates such as sodium or potassium citrate; especially wheat bran, and that the dye is a pharmaceutically tolerable dye.

Composition according to claim 4, characterized in that the electrolytes are a mixture of two or more of the compounds magnesium oxide, sodium chloride, potassium chloride, sodium bicarbonate, citric acid or sodium citrate, the lactase being a lactase 10 having a pH optimum between 5 and 8. , that the filler is wheat bran and that the dye is terra rubrum.

Composition according to any of claims 1-5, characterized in that the swelling agent is 20-55% by weight, the electrolytes and glucose are 40-60% by weight, the lactase or lactases being 0.01-5% by weight, the residual amount being one or more fillers, optionally one or more flavor corrective agents and / or one or more 20 colorants, the weight percentages being calculated by the finished composition.

Composition according to claim 6, characterized in that it consists of 40% by weight of swelling agent, 17.925% by weight of electrolytes consisting of 0.575% by weight magnesium oxide, 1.35% by weight citric acid, 2.4% by weight potassium chloride, 2.65% by weight sodium citrate, 4, 15 wt% sodium chloride, 6.8 wt% sodium bicarbonate, 35 wt% glucose, 0.025 wt% lactase, 6.8 wt% filler in the form of wheat bran and 0.25 wt% dye in the form of terra rubrum, where the weight percentages are calculated by the finished preparation . DK 153739 B 19

Composition according to any one of claims 1-5, characterized in that the swelling agent is 20-55% by weight, the electrolytes and glucose are 40-60% by weight, the lactase or lactase 5 is 0.01-5% by weight, of flavor-correcting substances in which the weight percentages are calculated by the finished preparation.

A composition according to claim 8, characterized in that it consists of approx. 43% by weight of the ground medium which is ground, approx. 19% by weight of electrolytes consisting of 0.617% by weight magnesium oxide, 1.45% by weight citric acid, 2.575% by weight potassium chloride, 2.845% by weight sodium citrate, 4.456 15% by weight sodium chloride, 7.3% by weight sodium hydrogen peroxide, 37.58% by weight glucose, 0.027% lactase and 0.2% by weight of flavor correction in the form of peppermint oil, the percentages of which are calculated by the finished preparation.