CS271877B1 - Method of d2 previtamine preparation - Google Patents

Abstract

During the preparation of the previtamin D2 through irradiation of an ethereal solution of ergosterol by UV radiation in the production system that consists of several reactive networks, the content of ergosterol in the product is periodically estimated with each reactive network, which leaves the reaction zone. According to the values achieved, the flow speed of the ergosterol solution through the reaction zone depends on the flow, ergosterol conversion degree and previtamin content in the product. The conversion degree is maintained in the range 30 to 40 percent and the content of the previtamin ranges between 23 to 28 percent by weight.

Description

BACKGROUND OF THE INVENTION The present invention relates to a process for the preparation of previtamin D21 3 by its kinetic controlled photochemical conversion of ergosterol.

In the production of vitamin D2, the preparation of previtamin D2 is performed by irradiating the ergosterol ether solution with UV radiation. In a system consisting of a system of several irradiation boxes, the feed of raw material into the individual boxes comes from a single container of the ergosterol ether solution and the product is collected in a common discharge line. As has been verified, in such a system, defined in terms of construction by the shape and size of the irradiation boxes with built-in UV sources, it is not possible to permanently create conditions to ensure an optimum degree of conversion in each individual reactor, even with the same design parameters. Analysis of the product in the common effluent channel gives only an average result which does not give an indication of the progress of the reaction in the individual boxes. As confirmed by analytical testing, the conversion values in individual boxes may differ by up to 50%. This affects both the yield of previtamin and the amount of undesirable by-products in the product. These deviations, which could be irrelevant for another type of production, are of great importance in the process described, since if a certain degree of ergosterol conversion is achieved, only the formation of by-products, and not previtamin, occurs during the subsequent irradiation. Thus, although the total conversion of ergosterol in the manifold from all boxes is desirable (i.e., some boxes achieve the highest, some lower conversion values), the previtamin yield is not maximal. Assuming a constant concentration of the ergosterol ether solution (C _Q ) and a permanently built-in UV source (intensity I _Q ), the conversion rate (K) in the system can be influenced only by the flow rate of the ether solution (Q) through the individual irradiation boxes. Based on these findings, the process for the preparation of previtamin D _{2 by the} photochemical conversion of ergosterol of the present invention is based.

The process consists in determining, in a production system consisting of several reaction cells in which the ergosterol ester solution is irradiated with UV radiation, for a period of one to four weeks, for each reaction cell, the ergosterol and previtamin content leaving the reaction space. values obtained, regulates the flow rate of ergosterol reaction space on the basis of relationship between flow rate, degree of conversion of ergosterol and containing previtamin in the product namely the relation wherein Q ₂ is a new flow rate of the reactor, Qj is the initial velocity "flow, the degree of conversion determined Based on an analytical determination of the ergosterol content of the product at a flow rate and K ₂ , the optimum degree of ergosterol conversion is selected, which is maintained in the range of 30 to 40%, corresponding to a previtamine content of 23 to 28% by weight. It has been found that an optimum composition of the product characterized by a previtamine content of about 26% can be achieved at an er.gosterol conversion rate of 30 to 40 ¾. The appropriate flow rate that ensures these parameters can be determined from kinetic equations

- dc _g / dt = I _Q f _B οθ ... ergosterol concentration dc _p / dt - I _o f _p Cp ... previtamine concentration

By adjusting the first equation we get the relation between ergosterol conversion and irradiation time t ¹ - ^c e ^{/ c} o = ^K = Ve * / ^c o% ^Q

If the reactor volume V is then the relationship between ergosterol conversion and flow rate is

K =

CS 271877 Bl

For a given specific embodiment, the quantities Ιθ, οθ, V are constant. The functional relationship f (or f _p, respectively) is determined analytically for a given Q, by determining the conversion (or previtamin concentration) of ergosterol in the irradiated solution. For small deviations of the conversion values from the desired one, the reactor flow rate can be adjusted according to the relation ^K 1 ^{/ K} 2 ^{= Q} 2 ^{/ Q} 1 where kde i is the degree of conversion determined from analytical determination of ergosterol content in the product conversion (in the range of 30 to 40%), Q ₂ is the new rate of solution flow through the reactor.

The process according to the invention is illustrated in more detail in the following examples.

Example 1

Samples of irradiated solutions were taken from the irradiation boxes 1 to 9 into which the ergosterol solution flowed at a rate of 25 l.hh. High-performance liquid chromatography (Varian AG-model 5020, 250 x 6 mm stainless steel column, Lichrosorb RP 18 column, methanol mobile phase) were used to determine the ergosterol conversion and prsyitamine content in irradiated solutions.

No. box conversion % previtamin% 1 43.4 29.5 2 35.0 25.9 3 24.2 18.4 4 30.4 22.8 5 47.2 30.7 6 54.0 32.4 7 38.0 27.4 8 39.5 28.0 9 38.0 27.4 average 38.9 value manifold 26.9

Based on these results, they were adjusted according to relationships

Q ₂ = K ₁ Q ₁ / K ₂ and Cl ₂ = Κ ₁ · 25/35 inlets into individual boxes as follows:

No. box nátok l.h 1 31 2 25 3 17 4 22nd

CS 271-77 01

No. box inflow lh ^-1 5 34 6 38 7 27 Mar: 8 28 9 27 Mar:

AND

Thus the ergosterol conversion in the individual boxes was adjusted to the desired value of 35%, the previtamin content to about 26. After adjusting the flow rates, the norm of consumed ergosterol is 1.346 kg / kg of previtamin.

Example 2

Of irradiated boxes 1-8, in which the solution was filled at 20 ergosterol ^l.h-1 are output samples irradiated solutions. Spectrophotometry (Perkin Spectrophotometer)

Elmer 555, second derivative method) the degree of photochemical conversion was determined - ergosterol conversion and previtamin content was determined by high performance liquid chromatography,

No. box conversion % previtamin% 1 49.5 31.7 2 54.2 33.1 3 55.2 33.1 4 50.1 32.0 5 49.5 32.0 6 51.4 32.8 7 48.8 31.7 8 48.8 31.7 average 50.9 value manifold 32.3

Based on these results, they were adjusted according to the relationship

Q ₂ = (Κ _χ .20) / 35 inlet into each box as follows:

No. box inlet l.h ' ¹ 1 20 May 2 31 3 32

CS 271877 Bl

No. box inlet l, h‘l 4 29 5 28 6 29 7 28 8 28

| Thus, by changing the flow rate, the ergosterol conversion in the individual boxes was adjusted to the desired value of 35 k and the previtamin content to about 26 k. After adjusting the flow rate, the standard of consumed ergosterol consumed 1.346 kg / kg previtamin.

The advantage of the process according to the invention is to increase the yields of previtamin by 5 to 15 k without any technical intervention, without modification of the equipment and the production process itself.

Claims (1)

OBJECT OF THE INVENTION i A method for the preparation of previtamin D by photochemical conversion of ergosterol, characterized in that the ergosterol and previtamin content of the product leaving the reaction space is determined analytically for each reaction cell at intervals of one to four weeks, and the flow rate of the solution of ergosterol through the reaction space is adjusted to basis depending on the flow rate, degree of conversion of ergosterol and content previtamu in the product expressed by the relation where a new flow rate of the reactor, the initial flow rate of the reactor is stupBň conversion obtained on the basis of analytical determination of ergofitňrnlu in the product at a flow rate Q ₁ and K is selected optimum degree of conv / n, kinase is maintained in the range of 30 to 40 ti, when the previtamin circulation in the product in the range of % by weight.