Biological products such as enzymes usually needs to be incorporated into specially designed formu-lations to improve product properties such as handling safety, applicability to specific applications, product stability, product standardization etc. Formulation of biological products is usually a non-optional requirement for creating a commercial useful and valuable product.
Our formulation area covers Dry formulation technology and Liquid formulation technology. Within the Dry formulation technology area we developed a range of granulated and immobilised enzyme prod-ucts for a vast number of applications. Furthermore, we have developed a process for directly com-pressive enzyme power. The latter technology involves preparing enzyme powder which has extraor-dinary good compression qualities and may directly be tabletted. One example of our immobilisation applications is a method for producing an immobilised enzyme preparation by mixing enzyme and a silica carrier in a granulator. This method is dramatically cheaper than comparable immobilised en-zyme preparations.
Our technologies within the Liquid formulation technology cover for example a liquid composition comprising enzyme and a phenyl boronic acid-derivative of specified formula. This composition has shown very promising storage stability results in liquid detergents.
Below are a few of our patents covering the Formulation area. If you are interested in one of the pat-ents do not hesitate to contact us for more details.
Title of Technology: Detergent additive granulate and method for production thereof
Abstract: This technology relates to a detergent additive granu
late and a method for production thereof. The detergent additive granulate com-prises a core with a primary detergent additive surrounded by a shellcomprising a secondary detergent additive, a binder, and granulating agents, and optionally a filler, and a protective coating between the core and the shell, whereby the shell comprises cellulose fibres or artificial fibres, and whereby the core facultatively comprises cellulosefibres or artificial fibres. The detergent additive granulate exhibits a high physical strength, and the primary and secondary detergent addi-tives are effectively separated from each other and/or from harmful environmental factors. The detergent additive granulate is produced by introduction of the components thereof into a granulating drum. This method of production is easily controllable and adapted for an industrial scale. The granulate and the method for production thereof is a further development of the granulate and the method for produc-tion thereof described in EP-A-0304332.
Detailed Description: The technology is a further development of the special embodiment of the invention described in EP-A-0304332, which comprises an en-zyme in either the core or the shell. However, the shell or the core in the detergent additive granulate does not necessarily contain an en-zyme; but the core contains one detergent additive (which may be an enzyme, here identified as the primary detergent additive), and the shell contains another detergent additive (which may be another en-zyme, here identified as the secondary detergent additive). In those cases where the primary detergent additive should be protected against the secondary detergent additive and/or environmental fac-tors, e.g. in cases where an enzyme is degraded by a bleaching agent and humidity in the atmosphere, or vice versa, there is a need for an effective separation between the primary and secondary detergent additives during storage. A
lso, there is a need for a granulate with high physical strength, and for a corresponding method of production, which is easily controllable and adapted for an industrial scale.
The purpose of the technology is the provision of a detergent additive granulate with a high physical strength and which contains a primary and a secondary detergent additive of the above mentioned kind,wherein the primary and secondary detergent additives are effectively separated from each other and/or from harmful environmental factors, and the provision of a corresponding method of production, which is easily controllable and adapted for an industrial scale.
The detergent additive granulate according to the technology com-prises a core with a primary detergent additive surrounded by a shell comprising a secondary detergent additive, a binder, and granulating agents, and optionally a filler, and a protective coating between the core and the shell, whereby the shell comprises cellulose fibres orartificial fibres, preferably in an amount of between 1.5 and 40% by weight of the shell.
Due to the protective coating between the core and the shell the two detergent additives do not harm each other during storage, and only during the application during wash the two detergent additives will be brought into contact with each other. Also, due to the content of the cellulose fibres or the artificial fibres in the shell the physical strength of the granulate is high.
The method for the production of the detergent additive granulate comprises the introduction of the core into a granulating drum, where-after sequentially the protective coating agent, the shell material and optionally a final dust suppressing coating agent, and furthermore cel-lulose fibres or artificial fibres in the appropriate amounts and at the appropriate stages, are introduced into the granulating drum.
It is to be understood
that any granulating drum can be used in rela-tion to the method. The entire process can be carried out in one of these granulating drums. Also, it is to be understood that the core can be coated with the protective coating agent in one granulating drum, whereafter the coated core can be isolated an transferred to another granulating drum for application of the shell, whereafter if wanted ap-plication of a dust suppression coating can be performed on the same granulating drum or another granulationg drum.
Glossary of Terms
| Term: |
Definition: |
| Drum granulator |
It is to be understood that the term drum granulator represents a broad category of granulator devices, comprising for instance pan granulators and granulation mixers |
Patent References
| Patent Number: |
Title of Patent: |
| EP 0458845B1 |
Detergent additive granulate and method for production thereof 1992 (Grant of the patent) |
| WO 9009428 |
Detergent additive granulate and method for production thereof 1990 (Publication) |
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Title of Technology: Compressible enzyme powder
Abstract: This technology relates to a directly compressible enzyme powder produced by mixing a liquid enzyme preparation with a suitable car-rier, using the principle of wet granulation, whereby the step of freeze drying and spray-drying is avoided. The resulting enzyme powder has extraordinary good compression qualities and may directly be tablet-ted. In a first aspect the present technology relates to a directly com-pressible powder, which comprises a carbohydrate and an enzyme. In a second aspect the invention relates to a process for the preparation of such a powder and to a tablet prepared from such a powder.
Detailed Description: Directly Compressible Powders.
The directly compressible powder comprises a carrier of carbohy-drate(s) and one or more enzymes.
In order to make the powder directly compressible the demands made on the carrier are quite large: It has to be a material with plastic prop-erties (so that the resulting tablet does not fall apart before use), on the other hand, when the tablet is used the carrier must be able to absorb liquid and make the tablet disintegrate. Moreover, as the pow-der is directly compressible, the powder should be free-flowing, which means that no flow-aids need to be added before tabletting. Lastly, as the resulting tablet may be ingested by humans, the carrier should preferably be non-toxic.
In order to make the powder directly compressible the water content of the powder may be of at the most 10% (w/w), preferably in the ran-ge of 3-5% (w/w), and the particles of the powder may be in the range from 50 to 1500 .mu.m, preferably in the range from 125 to 1000 .mu.m, more preferably in the range from 15
0 to 700 .mu.m.
Some carbohydrates or mixtures of carbohydrates posses the above mentioned properties of workable carriers. It has especially been found that starch, sugar and sugar alcohols or any mixtures thereof may give very good carriers. For instance, the starch may be maize starch, potato starch, rice starch, wheat starch, in fact any starch of vegetable origin. The sugar may be any mono-, di- or oligosaccharide, e.g. sucrose, maltose, lactose, galactose, fructose or glucose. The sugar alcohol may be any alcohol of a mono-, di- or trisac-charide, e.g. sorbitol, mannitol or xylitol. All these carbohydrates are available from normal commercial sources.
It has been found that a superior carrier consists of a mixture of maize starch and sorbitol. The maize starch is preferably present in an amount of 65-90% (w/w), while the sorbitol is preferably present in an amount of 10-35% (w/w), more preferably the maize starch is present in an amount of 75% (w/w) and the sorbitol in an amount of 25 k(w/w).
Enzymes
The enzyme could be any enzyme, e.g. one which may be used in the preparation of food and feed, a medicinal enzyme, an enzyme used for digestive aids, an enzyme useful for technical applications or any application where a precise and safe dosage of an enzyme is needed or desirable. The enzyme may be chosen from oxidoreductases such as peroxidases and glucoseoxidases, hydrolases such as carbohy-drases (e.g. amylases, hemicellulases, cellulases, inulinases, lac-tases and galactosidases), proteases (e.g. serin proteases and aspar-tic proteases), lipases and phytases, isomerases such as gluco-seisomerases or any mixture thereof. The enzyme may be of micro-bial, plant or animal origin. The enzyme may be a recombinant en-zyme or an enzyme recovered from its natural source.
The enzyme is added to the carrier as a liquid enzyme preparation. The liqui
d enzyme preparation may be an enzyme concentrate. An enzyme concentrate is produced by removing the production strain from the fermentation broth, for example by filtration or centrifugation, whereafter the liquid is concentrated to the desired enzyme strength, for example by ultrafiltration or by evaporation. The enzyme concen-trate may be stabilized by preservatives such as sorbate or benzoate and/or by stabilizers such as polyols (e.g. propylene glycol), boric acid, salts, sugar (e.g. glucose and sucrose) or sugar alcohols (e.g. sorbitol) or carbohydrates of low molecular weight. pH may be ad-justed and stabilized, for instance with buffer salts such as salts from organic acids, e.g. sodium citrate and sodium lactate.
Granulation
The powder may be made in accordance with well-known procedures of making wet granulation, for instance by using a convective mixer, followed by fluid bed drying, optionally followed by a sieving. The mix-ing is continued until the carrier is evenly wetted and a proper granu-late has been formed. Accordingly, it will be understood that the term "powder" is also intended to include granulates. The directly com-pressible powder may contain no lubricants, or a lubricant may be added to the carbohydrate(s) before granulation (preferred), or a lu-bricant may be added during the granulation, or a lubricant may be added at a separate mixing after the granulation and before the tablet-ting. The lubricant may be added in an amount of at the most 20% (w/w), preferably in an amount of 0.25-10% (w/w).
It is preferred to make a wet granulation consisting of a liquid enzyme preparation and a carrier, but the wet granulation may also consist of a carrier mixed with a spray-dried or freeze-dried enzyme powder whereto a liquid is added. The great disadvantage by using a spray-dried or freeze-dried enzyme powder is the dust problem described above.
In order t
o make a non-dusty powder the size of the particles is pref-erably at least 50 .mu.m. On the other hand, they may also be too large to be directly compressible. It has been found that the particles of the powder may be in the range from 50-1500 .mu.m, preferably in the range from 125-1000 .mu.m, more preferably in the range from 150-700 .mu.m.
It is important that the powder has the right water content in order to make it directly compressible. The water content is measured by loss on drying. A water content of at the most 10% (w/w), preferably a wa-ter content of 3-5% (w/w), may be accomplished by using any method known in the art, an example of which is conventional fluid-bed drying. The temperature of the fluid-bed should be adjusted to a level which does not deactivate the enzyme(s).
After fluid-bed drying the powder may be sieved, whereafter it is ready for tabletting.
Potential Applications
The directly compressible enzyme powder described herein may be used in all circumstances where a precise and safe dosage of an en-zyme is needed or desired, for instance in dairies where a milk clot-ting enzyme may be added as tablets, or in the digestive aid industry for various digestive enzyme tablets, or in technical applications, for instance for washing, dish-washing and denim-washing purposes.
In particular for use as digestive aids, the tablets may be provided with an enteric coating to protect the enzyme(s) from degradation by gastric fluid. Examples of suitable enteric coating agents are cellulose acetate phthalate (CAP, Cellacephate.RTM.), vinyl acetate crotonic acid copolymer (Luviset.RTM.), methacrylic acid, (meth) acrylic acid ester copolymer (Eudragit.RTM.) or hydroxypropyl methylcellulose phthalate. For a further description of enteric coatings and coating processes, reference is made to WO 87/07292.
Glossary
of Terms
| Term: |
Definition: |
| Directly compressible powder |
In the present context a directly compressible powder is a powder which may be directly tabletted without adding any excipients except possibly a lubricant. This means that no flow-aids and binders are added before tabletting, but a lubricant such as stearic acid, hydro-genated vegetable oil or Mg stearate may be added, if necessary. |
Patent References
| Patent Number: |
Title of Patent: |
| US 5,885,618 |
Compressible enzyme powder 1999 |
| WO 9500121 |
Compressible enzyme powder 1995 (Publication date) |