MXPA00001346A - Method for the continuous production of hydrolytically broken down and possibly substituted starch, use of hydrolytically broken down starch and device for producing same - Google Patents

Abstract

The invention relates to a method for the continuous production of hydrolytically broken down starch or hydrolytically broken down substituted starch products such as hydroxyethyl- or hydroxypropyl starch. The invention essentially consists of carrying out most of the hydrolytic breakdown in a pipe-shaped, temperature-controlled reactor (22) having no mixing elements. The remaining breakdown is carried out in one or more reactors (34-40) fitted with mixing elements (fine hydrolysis). The product obtained can be used both in the food industry and for medical purposes, especially as plasma diluent.

Description

PROCEDURE FOR THE CONTINUOUS PRODUCTION OF STARCH HYDROLYTICALLY DEGRADED OR ACCORDING TO THE REPLACED CASE, USE OF HYDROLYTICALLY DEGRADED AND DEVICE STARCH FOR YOUR PRODUCTION DESCRIPTIVE MEMORY Process for the continuous production of hydrolytically degraded starch or hydrolytically degraded substituted starch products. The invention relates to a process for the production of hydrolytically degraded starch or of hydrolytically degraded substituted starch products such as hydroxyethyl starch or hydroxypropyl starch, to the use of the products produced according to the invention in the medical field, in particular as plasma diluents , as well as a device for the production of hydrolytically degraded starch or hydrolytically degraded substituted starch products. It is known to degrade hydrolyzed starches and substituted starch products, such as hydroxyethyl- or hydroxypropylstarch. There is thus described in DE-OS 30 000 465 a process for the production of a starch hydrolyzate, in which α-amylase is used. The procedure there described works very complicated and must be carried out continuously not without difficulty. It is also applicable only limitedly. Also in the document DE-A1-33 13 600, a method for the hydrolytic degradation of starch is described, in which α-amylase, β-amylase or pullulanase is used, being able to replace the starch before or after the hydrolysis, by example with ethylene oxide. The degradation of hydroxyethyl starch to a product, which can be used as a plasma expander, among others, is described in EP-A1-0 402 724. The conduction of such a procedure in the continuous scale is possible not without difficulty. There is therefore a need for a continuous, economically functioning process that leads to products that can be used in the most diverse fields. As is known, rigorous requirements are imposed precisely on the products used in the medical field. On the one hand products that do not provoke any allergy in the patient are required, on the other hand the rate of degradation, that is to say the decrease in concentration within the first 24 hours, in the patient must be very high and the organ half-life time It must be short. In addition, the clinical applicability of degraded starch products depends in large part on the physico-chemical properties. With regard to this, reference is made to the work of Klaus Sommermeyer et al., Which have been published among others in Krankenhaus-pharmacie 8, (8271/8) (1987) and starch / Stárke 44 (5), 173-9 (1992). It is an object of the invention to provide a method for the continuous production of hydrolytically degraded starch or of hydrolytically degraded substituted starch products that is economically functional, with which the properties of the degradation products can be selectively incorporated, which can be carried with a small structure of apparatus and technique with respect to the process and which gives rise to products that can be used in particular in the medical field and in the technology of groceries. This object is solved by a method according to claim 1. In the claims 2 to 9, other advantageous embodiments of the method according to the invention are described. Another object of the invention is the use of the products, produced according to a process according to claims 1 to 9, as plasma diluents or for the production of dialysis solutions. Another object of the invention is a device for carrying out a process for the continuous production of hydrolytically degraded starch derivatives according to claims 11 to 13. For carrying out the process according to the invention, the usual starches can be used , such as, for example, potato starch, wheat starch, cassava starch and the like. Starches rich in amylopectin, such as Silo starch Milo ceráceo, corn starch or rice starch. Modified and unmodified starches can be used; the starch can also be used as partially degraded starch. As modified starches, hydroxypropyl- and preferably hydroxyethyl starch are used in particular. Modification can be carried out before hydrolysis, but also after hydrolysis. Preferably, however, it is modified, in particular it is ethoxylated, before hydrolysis. Modified or unmodified starch is used which is advantageously to be degraded as an aqueous solution or suspension, it being understood by suspension also that grains containing starch, which are present in water. The concentration of starch or modified starch can be adjusted in the solution or in the suspension in wide limits. The concentration can be adjusted from before the hydrolysis considering the objective of the desired use of the final product; It is also possible by choosing the concentration in relation to other parameters, such as hydrolysis temperature, residence times etc., to influence the profile of properties of the final product. Preferably, the concentrations are 25-30% by weight with respect to the total weight. After mixing with a hydrolyzing agent, in particular with a mineral acid, such as hydrochloric acid, it is heated in cold water to the desired temperature, preferably with the aid of a heat exchanger.

The suspension or the solution is then supplied to a tempered tubular reactor, whereby also a plurality of reactor units, which are connected one behind the other, must be understood by the reactor. The reactor is tempered at the desired hydrolyzing temperature, preferably at 70-80 ° C. The material to be hydrolysed is supplied to the tubular reactor from below, that is to say against the force of gravity, so that the suspension or the solution is pushed from bottom to top, that is to say in an upward direction. If several reactor units are used, all the reactor units are arranged in parallel and flowed from below in each case. Fundamentally, it is possible to carry out most of the hydrolysis in a single tube. However, several tubular reactor units can be juxtaposed, for example providing one gasket to another or an enzyme of another, which is preferred for production and handling reasons. The transfer of the hydrolysis material from one reactor unit to the next reactor unit can be carried out in a simple manner, for example with tubular connections, possibly by inserting regular pumps. The tubular reactors are designed or the flow rate is dimensioned in such a way that at least a major part of the hydrolysis, ie at least 60%, preferably 85-95% of the degradation, takes place in the tubular reactors tempered. This dissociation then takes place advantageously - as detailed below - as a first step in the form of a crude solution. The reactors Tubular tubes preferably do not contain any kind of mixing elements, to ensure a uniform forward movement of the suspension during hydrolysis without mixing. Sample collection sites may be provided. The already degraded product can then be transferred, for example 90%, to one or more other reactors, in which the hydrolytic degradation is carried out up to the desired production (second step in the form of fine dissociation). Preferably, the rest of the hydrolysis is carried out in the fine dissociation step in reactors having static mixing elements. With the help of these reactor units, it is possible to conduct the hydrolysis to its predetermined final value and perform fine tuning of the process. These reactors are therefore also advantageously provided with means for temperature conduction. In this way, it is possible to adjust precisely the degree of hydrolysis desired. The degree of hydrolysis is preferably examined with the aid of viscosity measurements. According to the invention, it is preferable to carry out a two step continuous dissociation process, consisting of crude and fine dissociation. On the other hand, however, it is also possible to carry out a one-step dissociation process corresponding to the raw dissociation, if the degradation is not to be conducted, it necessarily hydrolyzes to an exact predetermined degree of degradation, but can oscillate within certain limits. .

The flow of liquid material, which is to be hydrolyzed, against the force of gravity has the advantage that the solution / suspension layers that are in a reactor are practically not mixed, since by means of hydrolysis they are continuously formed starch dissolution products with decreasing chain length, which has the consequence that the liquid layers have an increasingly lower viscosity considered from the bottom of the reactor upwards. The reactor is in two stages with a viscosity gradient that constantly decreases - the degree of bottom up against the force of gravity. The solution to be treated during the hydrolysis is displaced with such velocity through the reactor that essentially allows an uninterrupted development of this viscosity profile. After the length of the reactor, ie reaction length during the continuous process, is fixed, the transport speed establishes the total reaction time, which is determined depending on the degree of hydrolysis selected. If an installation of multitubular reactors is used, then the connecting tubes are dimensioned in their cross section so that the layers of the same viscosity can be treated from one reactor to another essentially without interruption, that is without mixing the layers, for that the hydrolysis treatment can be carried out in the next reactor unit against the force of gravity. It can be included in the properties profile of the hydrolyzate obtained also by choosing the concentration of the solution of starting or starting suspension, as well as the molecular weight of the starch or the starch derivatives used, the degree of substitution, the hydrolysis temperature, the concentration of acids and the like. If modified degraded starch products are to be produced, the modification of the starch is preferably carried out before hydrolysis. It is possible and preferable with the method according to the invention to carry out in a completely continuous manner both the modification process and the hydrolysis process. In this way, starch, in particular degraded starch, can be mixed, for example for ethoxylation with ethylene oxide, with as much sodium hydroxide solution being supplied to the mixture that the desired pH is reached. This pH is preferably in the basic range and can have, for example, the value of 13. The mixing and the reaction can be carried out continuously, the conversion taking place preferably in one or several connected tubular reactors one after the other, provided with static mixers. The ethoxylated product is then mixed, as described above, to carry out the hydrolysis with hydrochloric oxide, and it is placed at the desired temperature and the hydrolysis is supplied. It was especially surprising that, with the aid of the process according to the invention, it is possible to degrade the starch and / or the modified starch in a hydrolytically continuous manner with a uniform profile in the final product. It was also especially surprising that obtained a hydrolyzate with a favorable distribution of molecular weights in the tubular rectors without mixing the solution by means of a static mixer with the displaced mixer, in particular that a very broad spectrum of molecular weights would not arise, as expected, by means of the formation of channels. The process according to the invention provides an essential simplification of the hydrolysis process and thus leads to considerable cost savings, since for acid hydrolysis processes only special steels (for example HASTELLOY) can be used, which is very expensive for the set of appliances, in which static mixers are present. By means of the process according to the invention, it is possible to produce in a directed and reproducible manner a hydrolysis material with determined properties. You can adjust exactly defined final values, with molecular weight, molecular weight distribution, substitution degrees and the like. These reproducible values can be achieved and constantly with a longer duration, while in the so-called intermittent operation the variations are very large and have to be controlled only with difficulty. This is true not only for the degradation of starch, but also for the degradation of modified products, so that it is possible to produce, in combination with a modification procedure for the most varied preparations for the purposes of application, with the desired properties.

The procedure is very flexible and can be widely automated. The method according to the invention can be carried out with an installation, as shown schematically in the drawing. With the 10 is indicated in the drawing a device for the continuous hydrolysis of starch and starch derivatives. From the station 12, the hydroxyethyl starch solution to be hydrolyzed is continuously supplied to a mixer / heat exchanger 14, which is connected to a vessel 16, which has hydrolyzing agent, for example hydrochloric acid. In the mixer / heat exchanger 14 an adjustment of the pH value is made to 1-2 and a tempering of the solution at a preselected hydrolysis temperature, for example 70-80 ° C. Next, the hydrolysis solution is supplied via a pump 18 with a predetermined pumping speed through a first line 20 to a reactor 22 (according to drawing 3 reactor units 24-28) as the reaction path (Main or coarse hydrolysis station), such that the hydrolysis solution has been against the gravity force below and above, as represented by the direction of the arrows in the reactor units 24-28. For this purpose, the reactor unit 24 at the place of operation is an inlet connection piece 23 disposed below and an outlet collection piece 25 disposed above. These connecting pieces 23 and 25 are also provided in the units of reactor 26 and 28 remaining. The pipe 20 is further dimensioned in cross-section, in such a manner that the hydrolysis layers arriving respectively to the reactor 24-28 do not mix essentially with one another. On the other hand, it can also be sufficient, however, that only one reactor unit 24 be used as the main hydrolysis station (represented by a dashed line with the 22), provided that it is sufficiently dimensioned in its volume. Essentially according to the invention, it is a matter of the slowly rising hydrolysis solution not being mixed in their layers with one another, ie the individual layers with their different hydrolysis states must not be mixed with one another. , similarly to the funds in the fractional distillation. Accordingly, a solution with a defined degree of hydrolysis can be extracted respectively at the upper outlet point of the reactor units 24-28, whereby a fine adjustment of the hydrolysis can then be carried out. The reactor units 24-28 are thus designated as the main hydrolysis station. In particular, it is the reactor units 24-28, not provided with mixing elements in their interior space, which can cause a mixture of the total hydrolysis solution. The hydrolysis agent, which correlates with the viscosity of the individual layers, must remain essentially unchanged, ie no mixing of the individual layers must take place with each other. The reactor units 24-28 advantageously have a temperature envelope 27, as they are symbolically shown in FIG. reactor unit 26 in the drawing. This temperature envelope, usually water, maintained at a given temperature therefore maintains the content of the respective reactor units 24-28 at the desired temperature. The last one is determined in each case, taking liquid tests in certain places of the reactor units 24-28 for the determination of the respective viscosity, that is to say of the respective degree of hydrolysis, and the degree of final hydrolysis is determined from this based on tables and the known transport speeds of the final hydrolysis degree. The design of the reactor units 24-28 is designed, so as to ensure a minimum flow velocity at a predetermined viscosity, to prevent a mixture of the respective layers due to the effect of diffusion. The latter depends among other things essentially on the viscosity. The lower limit of the flow rate is then found at approximately 3 cm / min., if the viscosity of the solution to be hydrolyzed is approximately 20 mPa.s. Advantageously, the flow rate is at 5-20, in particular at 10-15 cm / min. The ratio of the length to the diameter of the reactor units 24-28 is also determined by the flow rate of the solution to be hydrolyzed. Advantageously, this ratio is between 10: 1 and 20: 1. Advantageously, the main hydrolysis station 22 is connected through a second pipe 30 with a final hydrolysis station 32 (represented by a dashed line), as is characterized by the reactor units 34-40. These reactor units 34-40 are connected advantageously with a tempering unit 42, for example through a tempering jacket through which a liquid flows which is maintained at a certain temperature and which corresponds to the temperature jacket 27. Through this, it is possible to adjust the temperature conveniently for hydrolysis, which is conveniently monitored and controlled by means of the viscosity that is adjusted in each case. In addition, these reactor units 34-40 are equipped with the mixing elements 44 represented schematically, so that a uniform intermixing takes place within the rectors, to ensure a uniform hydrolysis. The tempering unit 42 is represented in the drawing exclusively in relation to the reactor unit 34 and may naturally be provided in the other reactor units 36-40. Likewise, the same is loaded from a tempered liquid source not shown. Hydrolysis up to 95% can take place, for example, in the main hydrolysis station 22, whereas only 5% of the desired degree of hydrolysis can be achieved in the final hydrolysis station 32. As mentioned above, the fine hydrolysis station 32 should be provided according to the invention, since there a hydrolysis product with a limited distribution of molecular weights is produced. If such a limited distribution is not necessary, then such a fine hydrolysis station 32 can be suppressed.

As shown in the drawing, the liquid to be hydrolyzed is transported in the station station 32 advantageously likewise from the bottom up to essentially eliminate the influences of the force of gravity. To stop the hydrolysis, the solution is mixed at the end of the hydrolysis in a neutralization station 46 with soda lye, which is transferred from the tank 48. Up to here, the container 46 is connected to a third pipe 50 of the station of hydrolysis 32. Next, the mixture is transferred for further treatment, for example diafiltration and spray drying, from the container 46 to other treatment apparatuses not shown. The invention is explained in more detail with the following example.

EXAMPLE 1 By adding water and bleach, a 30% starch solution is produced. From this, in a continuous ethoxylation plant, starch is produced by means of ethylene oxide, hydroxyethyl starch with a molecular weight of 1.4 million Daltons and is supplied with a volumetric flow of approximately 11.3 l / ha to a tubular reactor without elements. mixers The reactor has the dimension of approximately 2.6 m x DN 100. The ethoxylation is not an object of the invention, since a starch can also be used for the subsequent hydrolysis. To the hydroxyethyl starch solution, 0.2 l / hr of 25% HCl is metered in, before introducing it into the hydrolysis reactor; the reaction solution is also adjusted by means of a heat exchanger at a temperature of 70 ° C, whereby the pH value is adjusted to approximately 1.0. The hydrolysis reactor is maintained by means of tempering at 70 ° C, it being essential that the untreated solution of the reactor, which comes out without mixing elements, flows from bottom to top (against the force of gravity). The residence time of the solution is approximately 2 hours. This reduced the molecular weight from 1.4 million to 300,000 Daltons. In a thin hydrolysis section advantageously connected back, which consists of several reactors with static mixing elements, a final molecular weight (weight value) of about 250,000 Daltons is adjusted. The hydrolysis is then terminated by means of neutralization. The mixture is purified by means of diafiltration with the aid of a membrane with an exclusion limit of 50,000 Daltons. The dried product is outstandingly suitable as a plasma diluent.

Claims (13)

NOVELTY OF THE INVENTION CLAIMS

1. - Process for the continuous production of hydrolytically degraded starch derivatives, which are likewise substituted, by means of the conversion with a hydrolysis agent in an aqueous medium and the subsequent neutralization to interrupt the hydrolysis, characterized in that a solution or suspension is conducted continuously, containing the starch to be hydrolyzed, also substituted, through a reaction path essentially free of mixing against the force of gravity in the hydrolysis step.

2. Method according to claim 1, further characterized in that the reaction path has at least one tubular reactor (24-28), which has an inlet connection piece (23) arranged below it at the operating site. and an output connection piece (25) disposed above.

3. Method according to claim 1 or 2, further characterized in that, following the main hydrolysis according to claim 1, a fine hydrolysis is carried out in which the crudely hydrolyzed starch solution is supplied. to a tubular reactor (34) with mixing elements (44) at a predetermined temperature.

4. - Method according to one of claims 1 to 3, further characterized in that the tubular reactors (24-28 and 34-40) are arranged in the operating state essentially in vertical position and because the product to be hydrolyzed is conducted. from bottom to top.

5. Method according to one of claims 1 to 4, further characterized in that the tubular reactors are tempered at a predetermined temperature of 25-100 ° C.

6. Process according to one or more of claims 1 to 5, further characterized in that the main hydrolysis is carried out in the tubular reactor (22) tempered to 60-95%.

7. Method according to one or more of claims 1 to 6, further characterized in that etherified starch is used, preferably starch etherified with ethylene oxide and / or propylene oxide, in particular glutinous corn starch.

8. Method according to claim 3, further characterized in that the fine hydrolysis is carried out with several reactors (34-40) provided with static mixing elements (44).

9. Process according to one or more of claims 1 to 8, further characterized in that starch is partially ethoxylated continuously degraded with ethylene oxide in a basic medium, the ethoxylated product is acidified with a mineral acid, the Main hydrolysis at a reaction temperature of 60-100 ° C and the hydrolysis is terminated by neutralization with bleach and cooling.

10. Use of the hydrolytically degraded product that is produced according to one of claims 1 to 9, as a plasma diluent or for the production of dialysis solutions.

11. Device for carrying out the method according to claim 1 with a supply device (12) for starch solution; a container (16) for a hydrolyzing agent; a mixing and heating plant (14) for mixing the starch solution with the hydrolyzing agent and heating the mixture to a predetermined temperature; a pump arrangement (18) for supplying the mixture to at least one reactor (22); a pipe (20), which connects with one another complete units, as well as a neutralization station (46) to neutralize the mixture; the reactor (22) being disposed in the place of use essentially in the vertical position and having an input connection piece (23) located below and an outlet connection piece (25) located above and the arrangement being activated of pumps (18), in such a way that it continuously supplies the starch solution to the inlet connection piece (23) located below with a predetermined pumping speed so that the starch solution is transferred against the force of gravity through the reactor (22) to the outlet connecting piece (25).

12. - Device according to claim 11, further characterized in that a fine hydrolysis station (32) in the form of at least one reactor unit (34-40) having a hydrolysis station (22) as a main hydrolysis station is inserted behind the reactor (22). respectively mixing elements (44).

13. Device according to claim 11 or 12, further characterized in that the reactors (24-28 and 34-40) are respectively provided with a tempering unit (27, 42).