Note: Descriptions are shown in the official language in which they were submitted.
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The present invention relates to the preparation of
pre-mixes use~,l in the manufacture of foodstuffs for humans
and for animals, wnich pre-mixes incorporate minor but
essential ingredients such as oral vacc mes, vitamins, trace
elements and the like.
Pre-mixes are used to assist the blending of such minor
but essential ingredients into ~oodstuffs in a homoger.eous
manner, ~nd the invention is concerned with the preparation of
pre-mixes in the form of free-flowing particulate compositions
in which the minor but essential ingredient, or each such
ingredient where more than one is to be incorporated in a
common pre-mix, i9 dispersed unifo~mly throughout a carrier
material which forms the bulk of the pre-mlx~
For the purposes of this specification, an oral vaccine or
other minor but essential ingredient will be referred to aq an
"active ingredient".
Conventional pre-mixes wnich typically comprise the active
ingredient dispersed by mechanical means in a dry carrier such
as flour or other milled grain, tend to be unsatisfactory
because it is difficult to obtain a uniform dispension of the
active ingredient throughout the bulk of carrier by simple
mixin~, espeaially where the active ingredient is best handled
as a liquid. The ir,vention provides a method of making a
pre-mix involving simple steps and which can lead to greater
uniformity of distribution of the active ingredient.
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The invention provides a process for the preparation of a
pre-mix, in which process a dry particulate mixture of an
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edible inert p~wder and a lactose source, the lactose content
of the dry par~iculate mixkure being from about 20 to about 50%
by weight, is intensely agitated and while so lntensely
agitated-is sprayed with an aqueous solution or slurry of an
active ingredient, the solution or slurry being applied in an
amount of from about 1 to about 12~ by weight of
the dry particulate mixture.
Preferably the lactose content of the dry particulate
mixture is at least about Z % by weight, and ideally the
lactose content is at least about 25% by weight. Preferably
the lactose content of the dry particulate mixture is not
greater than about 45~ by weight, and ideally not greater than
about 35% by weight.
Preferably the amount of the solution or slurry applied to
the dry particulate mixture is at least 2% by weight.
Preferably the amount of the solution or slurry is not greater
than about 10~, and ideally not greater than ahout 6%9 by
weight.
The edible inert powder should comprise, together with the
lactose source, the bulk of the dry particulate mixture,
although other materials can be present in a total amount not
exceeding, say, 15% by weight of the dry particulate mixture
provided that any such additional material does not interfere
unduly with the flow propertieq of the dry particulate mixture
or with the desired properties o~ the pre-mix when formed.
Ihe edible inert powder can be any such powder which is
essentially lactose-free, and which is not more than sparingly
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soluble in water. A wide range of materials can be employed,
such a~: feed meals commonly used as ingredients in compound
I-oodstuffs, for example milled grain, bean meal and soya meal
provided that not too many oily or water-soluble components are
present; organic wastes and fillers used in am mal foodstuffs~
such as beat pulp, poSato pulp and feather meal; and inorganic
fillers such as kaolin, kaolinite, silica and chalk. Care
should be taken to ensure that the inert powder chosen is not
one whose maxLmum permitted level in the final foodstuff to
which the pre-mix is to be added unduly restricts the
formulation of the pre-mlx. Preferably the inert powder
chosen is one that can be included at a level of up to at least
about 0.5% by weight in the final ~oodstuff, and ideally at an
inclusion level of at least about 1.5% by weight. Ideal inert
powders are commercially-available flours such as wheat flour,
corn flour, rice flour and potato flour. Most
commerc_ally-available ~lours contain about 12% by weight of
moisture, and these flours can be used to produce acceptable
pre-mixes according to the invention. However, we prefer to
use dried flours, ie flours having a moisture content of less
than about 10% by weight. The use of dried Plour can impart a
longer storage life to the pre-mix.
The lactose source can be any commercially-available
lactose-containing compo3ition hav mg a sufficently high
lactose content and not containing a significant amount of any
other ingredient which can interfere with the formation or
properties of the pre-mix. A level of about 50% lactose by
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weight can be regarded as a practical minimum in most
circum~tances, and a higher level will generally be preferred.
Fat is an example of an ingredient which can be undesirable in
the lactose source, or for that matter in the pre-mix
generally, and hence lactose sources of high fat content should
be avoided. For this reason, skimmed milk is not recommended
for use as a major lactose source, although in some instances
minor amounts of skimmed milk powder may be incorporated
provided that the bulk of the lactose in the pre-mix comes from
some other source. ~ure lactose powder can be used as a
lactose source, but lactose powder is a relatively expen ve
commodity and is only preferred where, for taste reasons, other
lactose sources would be unsuitable.
In a preferred embodiment of the lnvention particularly
suitable for the preparation of pre-mixes useful in animal
feedstuffs, the lactose source mcorporated in the dry
particulate mixture is whey powder~ Whey powder typically
contains about 75~ by weight of lactose. In this embodiment,
the dry particulate mixture should comprise from about 40 to
about 70~ by weight of the edible inert powder and frcm about
60 to about 30% of weight of the whey powder. Preferably the
edible inert powder comprise at least about 50%, and ideally
at least about 55%, by weight of the dry particulate mixture.
Preferably the edible inert powder comprises not more than
about 65~ by weight of the dry particulate mixture. Preferably
the whey powder comprises at least about 35% by weight of the
dry particulate mixture, and preferably the whey powder
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comprises not more than about 50%, ideally not more than about
45%, by weight of the dry particl~1ate mixture.
A further preferred feature of the invention is the
incorporation of a small quantity of a weak edible acid in the
pre-mix. Preferably this acid should comprise from about 1 to
about 10% by weight of the pre-mix. Ideally the acid comprises
at least about 2% by weight of the pre-mix. Ideally the acid
does not comprise more than about 6% by weight of the pre-mix.
Although usually the acid be incorporated in the dry
particulate mixture to which the solution or slurry is applied,
it can in some instances be practical and useful to incorporate
some or all of the acid in the solution or slurry. Citric acid
is preferred, but other edible acids such as tartaric acid and
ascorbic acid can be used~ Edible acid salts such as sodium
di-hydrogen phosphate can be used where the presence of the
sodium will not lead to undue salt balance problem m the human
or animal consuming the foodstuff. We infer from in vit~Q
tests that the presence of the weak edible acid enhances the
release of the active ingredient when the foodstuff
incorporating the pre-mix enters the gut~
A further preferred embodiment of the invention is the
incluslon of a ~ood grade colouring agent in the aqueous
solution or slurry applied to the dry particulate mixture.
Preferably the colourirg agent is water-soluble. The
objective is to ensure that the distribution o~ the aqueous
solution or slurry throughout the dry particulate mixture can
be seen clearly. Thus the colour chosen should be one that
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is clearly distinct from the base colour of the dry particulate
mixture. In most embodiments of the invention, the base
colour of the dry particulate mixture will be essentially
white. Apart from this constraint, and the desirabili~y of
using a colouring agent that is cost effective, the selection
of the colour is entirely a matter of aesthetics.
The invention utilises the ability of lactose to absorb
small quantities of water to form a glass-like solid. In a
pre-mix prepared according to the invention, it is observed
that the pre-mix comprises a multitude of small hard particles,
each consisting of the edible inert powder bound by the lactose
glass, distributed throughout the bulk of the dry particulate
mixture. It is further observed that the active ingredient is
almost wholly located in the lactose-bound particles. This is
well demonstrated when a colouring agent is also included,
because it is apparent to the eye that the colour is
concentrated in the lactose-bound particles.
Arising from the critical selection of the proportl.ons of
the lactose to the edibie inert powder, the pre-mix of the
invention represènts a composition which has a uniform
distribution of particles containing the active ingredient
throughout its bulk and yet is a free-flowing particulate
composition having little tendency to lump or ~egregate.
Moreover, with the aid of the colouring ~gent when
incorporated, it i3 po~sible to perceive the unifot~
distribution of the particles co~taining the active ingredientO
The pre-mix has the additional advantage that the individual
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particules containing the active ingredients can be
physically separated from the bulk of the edible inert powder,
for example by hand or by screening, and assay of the active
ingredient can be performed readily on the separated particles.
The pre-mixes of the invention are useful for a wide
variety of active ingredients, However, a preferred use of
these pre-mixes is in the incorporation of oral vaccines in
foodst~ffs. The invention is ideally suited to the preparation
of pre-mixes containing endotoxins derived from bacterial
strains implicated in gastro-intestinal disorders~ Such
endotoxins, when substantially free from association with any
of the living bacteria, promote when administered orally a
highly effective immune response to the bacteria. In
particular this has been well demonstrated for Escherich a
coli~ and other gut~infective bacteria have proved susceptible
also. An oral vaccine for pigs has been developed in which the
endotoxins are derived from one or more of the E, coll strains 08, 045,
0138, 0139, 014t, 0149 and 0157O An animal feedstuff
incorporating such an oral vaccine is described and claimed in
our British patent No. 1,336,015. An analogous oral vaccine
for calves contains endotoxins derived from one or more of the
~_QQli strains 08, 09, 015, 026, 078, 086, 0114, 0115, 0137
and 0139. The calf vaccine can in addition usefully contain
endotoxins derived from SalmQnella dubL~ and/or SalmQnella
himurium. An animal feedstuff incorporating such an oral
vaccine is described and claimed in our British patent
No. 1~401~280J A similar oral vaccine for lambs, incorporating
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endotoxins derived from the E. coli strains 08, 09, 015, 020
078, 0114, 0137 and 013g, is described in our British patent
No. 1,462,384 and an animal feedstuff containing the oral
vaccine is claimed therein.
Alternative active ingredients include antibiotics such
as anticoccidial drugs; hormones; vitamins such as A and D, and
provitamins such as beta-carotene; trace elements and minerals,
such as sources of calcium, phosphorous, iron, manganese,
copper and iodine; growth promoters; and ~lavours and perfumes.
The need for such active ingredients to be present in
foodstuffs for human and animal consumptton is well
known and well-documented in the technical literature, as also
is the nature of such active ingredients and the extent to
which they are available commercially. The nature o~ such
active ingredients ~er se does not form part of the invention.
The concentration of the active ingredients in the aqueous
solution or slurry is not critical, subject to the proviso that
the viscosity of the solution or slurry must be such that the
solution or slurry can be sprayed as very ~ine droplets onto
the dry particulate mixture.
Pre-mixeq comprising more than one ac~ive ingredien~ can
be prepared. All of the active ingredients involved can be
included in a single aqueous solution or slurry i~ desired.
In some instances, the non-simultaneous application of a
separate solution or slurry for individual active ingredients
can be practical and advantageou3. Where separate solutions or
slurries are used1 the incorporation of a distinctly different
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colouring agent in each solution or slurry can enable particle~
containing the different active m gredients to be identified in
the resulting pre-mix.
Physical preparation of the pre-mix of the invention can
be accomplished us.ing any conventional equipment capable of
intensely agitating a particulate material and simultaneously
finely spraying a liquid onto the particulate materiall
Horizontal ribbon mixers can be used, and vertical spray mixers
such as the "Schugi"*mixer represent alternatives. If desired,
the pre-mix can be prepared in a ~luidised bed equipped with a
spray head for the solution or slurry.
It will be appreciated that the particle size of the
materials making up the dry particulate mixture, and also the
droplet size of the solution or slurry when sprayed thereon,
will influence the particle sizes found in the resulting
pre-mix. By varying these parameters, it is possible to
produce pre-mlxes having different particles size distribution
and in which the active ingredient is present m a large number
of very minute particles, or in a lesser number of relatively
large particles. Thus the invention makes it possible for a
pre-mix to be tailored to meet different product requirements.
The general principles governing the effects of substrate
particle size, solutionJslurry viscosity, spraying nozzle
design and spraying pressure are well known to those skilled in
food techrology and related arts, and the techniques required
for the physical production of a pre-mix in accordance with the
invention are in themselves quite standard technology.
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As far as the particle size of the ingredients in the dry
particulate mixture is concerned, we have found that standard
co~mercially-available ingredients are quite adequate.
~tandard flours, in which, for example, all but a trace of the
particles are less than 200~ in diameter, are perfectly
suitable. So too are commercially-available whey powder and
lactose powder. In general, it can be stated that each
ingredient of the dry particulate mixture should preferably
have a particle si~e such that at least 80% by weight of the
ingredient will pass through a 500~ screen, and ideally at
least 90~ by weight of each ingredient will pass through such a
screen.
Preferably the quantity of solution or slurry applied to
the dry particulate mixture, and the spraying conditions used,
should be selected such that the resulting pre-mix contains at
least about 1000 lactose-bound particles containing the active
ingredients per gram of pre-mix. Ideally a pre-mix of the
invention will contain an even higher number of lactose bound
particles containing the active ingredients9 and a level of at
least about 2000 lactose bound particles containing the active
ingredient per gram of pre~mix should be aimed for. In an
ideal pre~mix according to the invention, at least about 95~ by
weight of the active ingredient will be contained in distinct
lactose-bound particles separable from the bulk of the
pre-mix.
A pre-mix of the mvention can be incorporated in a human
or animal foodstuff by simple admixture, the proportion of
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pre-mix per unit weight of the foodstuff being chosen with
regard to the concentration of the active ingredient present in
the pre-mix and the concentration of the active ingredient
desired in the foodstuff. In the preparation of compounded
animal feedstuffs, the pre-mix can be added to nutrient
materials at the milling stage. The nature of the nutrient
materials that comprise the human or animal foodstuff in which
the pre-mix is incorporated i5 not critical to the invention.
Any of the usual protein, carbohydrate and fat materials can be
used.
The pre-mix of the invention is a vendable product in its
own right, as it can be sold for incorporation in foodstuffs
made by different manu~acturers.
Specific embodiments of the invention will now be
described, by way of example only.
Exa~
250 kg of a dry particulate mixture was prepared by mixing
together the following ingredients:
Ingredien~ ~5~U ~ b~
Dried wheat flour 58
Cheese whey powder 38
Citric acid 4
The dried wheat flour was a commercial product containing
4,8% moi~ture by weight. Over g9% by weight of the flour
passed through a 195~ screen. The cheese whey powder was also
a commercial product, containing 6.1% by weight of moi~ture.
Qver 99% by weight of the whey poT~der passed through 53~
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screen, and over 68~ by weight passed through a 195u screen.
The dry particulate mixer was fed to a Gardner horizontal
ribbon mixer fi~ted with 6 hollow-cone M2 ~praying nozzles.
While the dry particulate m~xture was intensely agi~ated in the
mixer, it was sprayed with 12.5 litres (5% by weight) of an
aqueous slurry of E. coli endotoxin material prepared according
to procedure A of Example 3 of British patent speciPication No.
1,366,015 and in which slurry had been incorporated 125 gm of a
commercially-available food-grade red azo dyestuffO The
activity of the slurry was 3000 haemagglutination un~ts of
endotoxins for each ~_Qli serotype per ml. Spraying time was
30 minutes. Mixing was continued for several minutes after
completion of spraying, to ensure even distribution of the
pre-mix ingredients.
The pre-mix so ~ormed was seen to comprise a free flowm g
powder of very pale pin~ colour uniformly throughout which was
di~persed a large number of tiny, hard, intensely-coloured red
particles.
The intensely-coloured particles could be readily
serparated from the bulk of the pre-m1x, and analysis revealed
that over 98% of both the dyestuff and the vaccine activity
reqided in the intensely-coloured particles.
A particle size analysis of the pre-mix yielded the
following result:
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' Dre-mix
1999 0.4
800 - 1999 3.4
600 - 799 2.6
~: 350 - 599 L~oO
250 - 349 6.4
149 - 249 17.0
125 - 148 11.4
74 -. 124 38.6
< 74 16.2
A particle count made on a ~ample of the pre-mix revealed
that there were approximately 5000 intensely-coloured
lactose-bound particles per gram of the pre-mix.
This pre-mix was incorporated at levels of 0.5, 1.0 and
1.5% by weight in a standard feed composition ~or young pigs.
The feed composition was milled and pelletted to give a creep
feed consisting of small pellets, one gram of feed cGnsisting
of approximately 10 pellets. On average, each pellet would
have contained 2.5 lactose-bound particles at the 0.5%
inclusion level. Pi~s fed on these feeds accepted them
readily, and enjoyed the prophylactic benefits described in our
British patent ~pecification No. 1,366,015.
~xam~les 2 an~ ~
The procedure of Example l was repeated on two further
250kg batches of a dry particulate mixture of composition
identical to that used in Example 1. In this instance,
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however, both batches were ~prayed with 7 litres (2.8~ by
weight) of the aqueous slurry, and m Example 3 the M2 spraying
no~zles were replaced by M6 nozzles. The spraying time in
Example 2 was 12 minutes, and in Example 3 it was 5.5 mm utes.
As in Example 1, a pre-mix consisting of a large number
of minute intensely-coloured particles dis~ributed uniformly
through a pale-coloured powder resulted. The M6 nozzle
induced the formation of some larger particles, consistent with
the larger droplet size associated with this nozzle. However,
the pre-mix of Example 3 was in no way inferior to that of
Example 2. A particle size analysis of each pre-mix gave the
following results:
partiLQdiameter (~1 ~ bv wei~ht of
vre-mix
> 1g99 0.2 0.4
800 - 1999 0.4 3.6
600 - 799 0.6 3.0
350 - 5g9 2.2 2.2
250 ~ 349 6. 4 2. 6
149 - 249 50.6 29.6
125 - t48 11O4 13.4
74 - 124 15.0 29.6
'~ 74 13.2 15.4
The pre mixes of Example 2 and Example 3 wer~ each
incorporated in standard pig feed compositions, and gave
excellent results in feeding trials,
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