DE2727778A1 - VITAMIN PRODUCT - Google Patents

Description

FROM KREISLER SCHONWALD MEYER EISHOLD FUES FROM KREISLER KELLER SELTING

PATENT LAWYERS Dr.-Ing. by Kreisler f 1973

Dr.-Ing. K. Schönwald, Cologne

Dr.-Ing. Th. Meyer, Cologne

Dr. Ing.K. W. Eishold, Bad Soden

Dr. J. F. Fues, Cologne

Dipl.-Chem. Alek von Kreisler, Cologne

Dipl.-Cln-iii. Carola Keller, Cologne

Dipl.-Iny. G. Seltiiiy, Cologne

Farmos-Yhtymä Oy. Tengstrominkatu 6 Turku 36, Finland

5 COLOGNE 1

DLlLt |;. ·,. · Ι 41 <l IAUi, AM HAUHTUAIINHOI-

2o. June 1977 AvK / Ax

Vitamin product

7098 * 1/0832

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The invention relates to a stabilized vitamin product, which is particularly suitable for feeding to animals is provided. The properties of the product in terms of Stability, absorption, accumulation, utilization and palatability of vitamins, in particular Vitamins A, D, E and K, are extremely beneficial.

The use of vitamin solutions that contain fat-soluble vitamins and are "water-soluble" by emulsifying have been made, has increased in the feeding of animals. This is due, among other things, to the automation of the Feeding, which is a result of increased units of livestock. The need for additional Vitamin has increased as a result of increased production output (stress) and improved feed conversion. The supplementary feeding of vitamins has become routine. In most cases, the It is easiest to administer vitamins separately as a liquid feed preparation together with the drinking water.

Oral emulsions containing vitamins A, D, E (and sometimes K) or mixtures of these vitamins, are advantageously produced by taking an oily vitamin raw material together with an emulsifier under vigorous Agitation is incorporated into a base or vehicle, usually water. When comparing the "water-soluble" products obtained in this way in terms of their utilization were usually only that Absorption capacity for the emulsified vitamin (e.g. vitamin A acetate / palmitate) is considered, but not the possible effect of the carrier.

According to the invention has now surprisingly been found that by adding a sugar alcohol or

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a mixture of sugar alcohols to form the basis of the vitamin emulsion is possible, the microbiological resistance, To improve the stability, absorption, utilization and palatability of the vitamin emulsion. The sugar alcohol is expediently in an amount of 5 to 30% dry matter, based on the total weight the vitamin emulsion added. The addition of 15% is advantageous. It was found to be particularly beneficial Xylitol as well as "molasses", which are a by-product in the manufacture of xylitol from plant material how wood is obtained to add to the carrier of the emulsion.

The above by-product obtained from birch wood is a yellowish-brown sweet Liquid with a specific gravity of about 1.22 as a 50% aqueous solution. It has the same Caloric value and the same sweetening value as glucose. The by-product contains several sugar alcohols and has generally the following composition, calculated as dry matter:

Table I. Xylitol 15-25 Wt% Arabitol 20-35 It Mannitol 15-25 Il Sorbitol 5-15 It Dulcit 5-15 Il Rhamnite 5-10 ti Other sugar alcohols 2- 5 It Decomposition products 2- 5 It

In the newer process, the recovery of xylitol has been improved. The composition calculated as dry matter can vary within the following limits:

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Table II

Xylitol 6-18% by weight

Arabit 9-21

Mannitol 13-19

5 sorbitol 8-12 "

Dulcit 5-11

Rhamnite 4-6 "

Reducing sugars 8-15 "

Other polyols 6-14 "

It is known from the literature that, for example, xylitol stimulates the functions of the liver and its activity of cells increases. It is also known that the microbes in the mouth are not able to use xylitol as Utilize energy source, and that in the liquid of the rumen (in vitro) the sugar alcohols for a long time preserved without decomposition (E. Poutiainen and coworkers Proc. Nutr. Soc. 294th Scientific Meeting, London, (1976) pages 140-141A, and Dl-PS (patent application P 27 10 930.4 of the applicant).

^T he invention is illustrated by the following examples in connection with feed supplements, which proved to be particularly advantageous.

Example 1; Microbiological comparison

The microbiological applicability of various basic additives to the vitamin emulsion was examined. As additives xylitol and a by-product from xylitol manufacture were used. In the comparison tests

Now sucrose was used. The experiment / with

pure water.

In the tests, solutions were each containing 15% xylitol, 15% by-product or 15% sucrose, calculated as dry matter, and a solution that contained contained distilled water, with a microbial susceptibility

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pension contaminated, which contained the following microorganisms:

Escherichia coli (gram-negative rods) Staphylococcus epidemus (gram-positive cocci) 5 Saccharomyces carlsbergensis (yeast)

The one-night-old precultures were stirred to form a mixed suspension, which in proportion was diluted 1: 1000. 1 ml of each of these suspensions was pipetted into 100 ml of each test solution, The solutions were transferred to an incubation chamber which was kept at a temperature of 35 ° C.

The concentrations of the microorganisms in the solutions were followed during one month by the cultivations on bacterial count agar and on Saboraud agar. The results of the experiments are mentioned in Table III. The numbers in this table indicate the concentration of the microorganisms related to those mentioned Times as the number of cells per ml.

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Incubation
Time,
Days

By- product of the xylitol production

Mixed suspension

Number of the number of bacterial yeast cells on len Saboraud count agar per ml agar

per ml

Table III Additive

Distilled water

Mixed suspension

Count of the number of bacterial yeast cells on len on Saboraudpro counting agar ml agar

per ml

Xylitol

Mixed suspension number of bacterial yeast cell number on len on Saboraud count agar per ml agar

per ml

Sucrose

Mixed suspension

zani aer £ at aer bacteria Yeast cellar cells on len on Counting agar Saboraud per ml Agar per ml 35,000 200 4,300 3 730 6,000,000 100,000 54,000 34,000

1
2
9

14th
41

21,000

100

60

500 300

1,260,000 1,340 OGO

25,000
500
170
180

3,000 100 110 120

22,000

300

120

600

200

60

200

The test results show that when comparing sucrose, xylitol, the by-product of the Xylithermaking and distilled water the sucrose solution clearly prove to be the best breeding ground for that Microorganisms proved. Xylitol and distilled water were equivalent, proof that xylitol is a poor breeding ground for microorganisms. However, under the experimental conditions, the xylitol appears to be growing also not to inhibit the microorganisms to a greater extent. The by-product obtained from xylitol manufacture apparently contains components that make the Inhibit the growth of bacteria but not yeast. In summary, it can be said that bacteria thrive poorly on sugar alcohols or at least as poorly as in pure water.

15 Example 2

Microbiological comparison of a vitamin solution containing a sugar alcohol with a medicinal preparation.

In this experiment, two vitamin solutions were tested with regard to their tendency to attack by microorganisms resembled. The preparations used were a water-based vitamin solution (A-D-E-VIMIN® / Astra) and a Corresponding solution of vitamins A, D and E, the additional 15% sugar alcohols (by-product of xylitol manufacture, Table I), calculated as dry matter and based on the total weight of the solution. The contamination and the experimental methods were that same as in Example 1. The results are shown in Table IV below.

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Table IV

Microbiological comparison of a vitamin solution containing sugar alcohol with a medicinal preparation.

Incubation
Time,
Days

Vitamin solution

A-D-E-VIMI

Astra

Mixed suspension

Counting agar,

Bacterial cells / ml

Saboraud agar, yeast cells / ml

14th

41

52,000,000 750,000 190,000 240,000

25 600

40 0OO

16O

110

82

ADE solution, containing the by-product of the XyI it division.

Mixed suspension counting SaboVäudagar, agar, bacteria ^ yeast cells / ml cells / ml

31,000
110

700 1OO

The above results show that the ^{water-based preparation 11} ADE-VIMIN ^R "is a much better nutrient medium for microorganisms than the corresponding sugar alcohol-containing solution of vitamins A, D and E. From the vitamin solution containing the sugar alcohols, the population of the microorganisms disappeared after Inoculation very fast: after one day the bacterial content had fallen to less than 1/100 of the amount after inoculation, ie the vitamin solution containing the sugar alcohols is microbiologically very stable.

The same inoculation attempt was also made with periodic Repeated inoculation with two additional known vitamin products. The test results are in Table V named.

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Tabel

Growth of microorganisms in various vitamin products

Time
Days ■ -α
ο Vitamin A-D Orion Saboraud-
Agar, yeast
cells / ml 700 OCO V i t a m i η ρ r ο d Saboraud-
Agar, yeast
cells / ml u k t Saboraud-
Agar, yeast
cells / ml Vitamin ADE
15% sugar alcohols suspension Oi Mixed suspension <100 25,000 Vitamin A-D-E Astra 90 COO Vitamin A-E 40,000 Mixed ί Saboraud-
Agar, yeast
cells / ml *% Counting agar,
bacteria
cells / ml 600 - Mixed suspension 2,000,000 2,000 Counting agar,
bacteria
cells / ml <100 O 3 <I00 550 9CG CCO Counting agar,
bacteria
cells / ml 2 OCC 000 ) Raw to 5,000 <I00 <100 CO
0 * 9 600 <100 j 4 CCG 000; 600 COC 900 200 COO Mixed suspension <100 <100 <100 * ° 10 ^Β 150 2,000 200,000 i 2C CCO 90 COO 250,000 Counting agar,
Bacteria-
cells / ml 2,000 <100 <100 11 <100 3,500 2,000 <100 ί <100 2C 000 1 CCC 5,000 <100 <ioo 2 000 ' 17th 3,000 <1CO <I00 2OC COO 300 COO 800 <100 2,000 <ioo ^ ₁ 18 ^B j OCC COO 250,000 600 CCG <100 SOO 000 <1CO <100 19th 1,500,000 1OC COO 250 COO <100 3CO <10C 70,000 24 - 'ίο: coo 40,000 2,000 <100 2CC COO <IC0 ₂₅ B t
3 GOG COO ^: 2 CCC 000 4 OCC 000 <I00 700,000 <I00 <100 26th ι 1 CCC 000 i COC OCC <100 4,000 <I00 90 000 ^ * 32 500 OOC 500 COO 2,000,000 <100 400,000 <I00 NJ 49 ¹ I COC COC 2,000,000 <100 <100 <100 ■ 2 COC COO <100 <10C ^<1OB S i 500 COC 4 OCO COO <100 4OC 000 ' 5,000 <100 <100

B «= inoculation

The addition of sugar alcohol gives the vitamin product high resistance to attack by microorganisms. The inoculated microorganisms disappeared in any case within one day.

5 example 3; Vitamins stability

In this experiment, the shelf life of the vitamins at different temperatures after the addition of Sugar alcohol (by-product of xylith production, Table I) to the vitamin emulsion in an amount of 15%, calculated as dry matter and based on the total weight of the emulsion. As vitamin components the emulsion contained 30,000 I.U. vitamin A, 3000 I.U. vitamin D and 30 mg vitamin E per ml The basis was distilled water, to which the sugar alcohol and the other necessary agents were added became.

The preparation was frozen (-20 ⁰ C) and 10 days maintained at this temperature, after which thawed and 53 days was maintained at room temperature (20 ° C). The product was then stored in the refrigerator (+4 ⁰ C). Samples were taken from the preparation during the freezing period (3 days), after storage at room temperature (53 days) and after storage in the refrigerator after storage for a total of 9 months. The samples were examined for their vitamin content after each period. The results are given in the table below.

Table VI

Storage stability of the vitamin emulsion at different temperatures.

Laqerzelt temperatur, ⁰ C vitamin E vitamin A.

3 days -20 36.7 32 900

53 days +20 34.7 31 6OO

9 months +4 * 33.9 31 460

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The test results show that the vitamin content of the preparation under changing temperature conditions is preserved for a long time.

Example 4
Movement of radioactively labeled vitamin A in the stomach

intestinal canal

In these experiments, the movement of radioactivity in the gastrointestinal canal for solutions of vitamins A, D and E was measured with the aid of tritiated vitamin A, A ₁ (all-trans) ^1-3 H (N), on three groups of five SPF each -Mice (specific pathogen free) examined. The test results are given below in Table VII, which shows the radioactivity found in the gastrointestinal tract 2 hours after oral administration as a percentage of the amount administered. Xylitol and the by-product of xylitol manufacture (Table I) were used as the basic additive for the vitamin emulsion. At the same time, a series of tests was carried out in which pure water was used as the basis. The proportion of sugar alcohol was 15%, calculated as dry matter and based on the total weight of the emulsion.

Table VII Movement of radioactivity in the gastrointestinal canal

Part of the gastric radioactivity

intestinal canal xylitol by-product pure water

Stomach 3.40 ^ 0.24 * 4.64 + 0.12 ^XX 5.83 + 0.20

Small intestine, 6.50 + 0.26 6.26 + ^ 0.24 7.56j_1.00 front part

Colon, 2.86 + ^ 0.08 3.12 + _0.16 2.62 + 0.16 back part

Large intestine and rectum 2.76 + 0.02 3.16 + 0.12 3.68 + 0.38 ~ "~~

Total salary 15.52 17.16 19.74

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The values in the table are means + _ standard errors of the mean.

The concentrations of xylitol and by-product in the stomach differ in a statistically significant manner of the values obtained with pure water. The significance of the difference between xylitol and water is (according to Student's t-test) P <0.05 and the corresponding value for the by-product P <0.01, i.e. the difference is statistically very significant. The values for the other parts of the gastrointestinal canal differ do not differ significantly from the values obtained with water, i.e. significantly less radioactivity was found in the stomach of the test animals when the basis of the labeled vitamin emulsion was sugar alcohol contained. This means that the radioactivity either through resorption in the organism or with the excrement disappeared.

Example 5

Excretion of radioactively labeled vitamin A with the excrement

The experiment was based on that described in Example 4 Way carried out, with the transition of isotope-labeled vitamin A in the excrement of the test animals was established. A vitamin preparation was given in the manner described in Example 4 orally, groups of each administered to five SPf mice. Samples of the feces were taken daily for a period of 30 days. the Results of measurements of radioactivity of the collective The excrement samples taken are shown below in

30 named Table VIII.

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did from Table .. VIII Laboratory animals Radioactivi XyI it Excrement samples of the Pure water time in
Days By-product

5 1 7.62 8.86 13.20

2 0.04 0.06 0.12

3 -

The radioactivity of the emulsions whose bases contained xylitol and the by-product of xylitol manufacture, had thus disappeared from the gastrointestinal canal (absorption area) faster than with an emulsion based on pure water, as Example 4 shows. However, there is a corresponding increase in the excrement not to be determined. Rather, the opposite is the case,

15 as example 5 shows.

Less than 1% of the administered amount was excreted in the urine. Statistically significant differences between the groups were absent.

Example 6

Absorption of tritiated vitamin A through

the organism

From the results of the experiments described in the preceding examples, it was expected that the radioactivity from the xylitol-based solutions and by-product faster than from the water-based solutions would pass into the blood serum, liver and other internal organs. To prove this, received SPF mice orally as a single dose of 450 IU vitamin A (marked with tritium) as a solution of vitamins A, D and

E. The radioactivity of the blood serum and that of the liver as a percentage of the dose 2 and 6 hours and 1, 2, Determined 3 and 7 days after administration. The results are given in Table IX and in the figure graphically represented.

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Hours. O Tabel 0. IX .03 0.29 + 0.01 Pure water 0 .02 Hours. O radioactivity 0, .01 0.28 + 0.01 0.29 + 0 .01 Day O Xylitol 0. , 01 0.16 <+ 0.01 0.26 + 0 .01 Days O .38 + 0. of the blood serum 01 0.13 <+ 0.01 0.16 + 0 .01 Time Days O .30 + 0. By-product 01 0.09 <+ 0.01 0.13 ο .01 2 Days O .16 + 0. 0.05 <+ 0.01 0.08 <f 0 .01 6th .12 + 0.07 + 1 .08 <+ 2 .06 <+ 3 7th

In the table, the value for xylitol after 2 hours differs very significantly (P <0.001) of the corresponding value for water. The corresponding value for the by-product is inconsistent. Both other values could not find any significant differences

15 can be determined.

In the figure, the corresponding results of the measurement of radioactivity for the liver are graphically shown. The results are the mean 4 ^ standard errors. Those obtained with xylitol after 2 and 6 hours Values differ to a statistically significant extent from those obtained with pure water Results. The level of radioactivity measured in the kidneys, brain and heart remained below 1%. Statistically there were significant differences between the groups

25 does not exist.

^From Examples 4 to 6 it can be concluded that sugar alcohols, in particular xylitol and the by-product formed during the production of xylitol from vegetable material, stimulate and increase the absorption of vitamins through the gastrointestinal canal and their accumulation and utilization in the organism.

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Claims (5)

claims 070777Q Vitamin product made from water-emulsified fat- and water-soluble vitamins, in particular an emulsion containing vitamins A, D, E and K, characterized in that it also has one effect on the stability, absorption, enrichment, utilization and palatability of the emulsified vitamins Contains sugar alcohol or a mixture of sugar alcohols in an amount of 5 to 30% by weight, calculated as dry matter and based on the total weight of the product. 2) vitamin product according to claim 1, characterized in that it contains 15 wt .-% of the sugar alcohol or the mixture of sugar alcohols. 3) vitamin product according to claim 1 and 2, characterized in that it contains xylitol as the sugar alcohol. 4) vitamin product according to claim 1 to 3, characterized in that it is a mixture of sugar alcohols Contains by-product that is obtained from the production of xylitol from plant material, e.g. wood, and as contains main sugar alcohols xylitol, arabitol, sorbitol, mannitol, dulcitol and rhamnitol. 5) vitamin product according to claim 1 to 4, characterized in that it is in liquid or dry form is present. 7098R1 / 0832 ORIGINAL INSPECTED