GB1574269A - Non-animal lipase preparations having activity - Google Patents
Non-animal lipase preparations having activity Download PDFInfo
- Publication number
- GB1574269A GB1574269A GB728578A GB728578A GB1574269A GB 1574269 A GB1574269 A GB 1574269A GB 728578 A GB728578 A GB 728578A GB 728578 A GB728578 A GB 728578A GB 1574269 A GB1574269 A GB 1574269A
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- Prior art keywords
- weight
- lipase
- preparation
- protein
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/18—Carboxylic ester hydrolases (3.1.1)
- C12N9/20—Triglyceride splitting, e.g. by means of lipase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
(54) NON-ANIMAL LIPASE PREPARATIONS HAVING IMPROVED ACTIVITY
(71) We, DEUTSCHE GOLD-UND SILBER-SCHEIDEANSTALT VORMALS
ROESSLER, a body corporate organised under the laws of Germany of 9 Weissfrauenstrasse, 6 Frankfurt Main 1, Germany, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:
This invention relates to non-animal lipase preparations having improved activity.
The invention is an improvement in or modification of the invention 9f our prior patent application No. 35255/77 (Serial No. 1546328) which is referred to herein as the main patent.
The main patent describes and claims an enzyme preparation containing a lipase of non-animal origin and, as stabiliser, 10 to 50 parts by weight (based on 1 part by weight of lipase) of a mixture of the following constituents: 40 to 90% of lactose; 8 to 50% of whey protein; 0.1 to 7% of milk fat; 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = by weight).
The main patent also describes and claims a pharmaceutical preparation containing a lipase of non-animal origin and from 10 to 50 parts by weight (based on 1 part by weight of the lipase) of a mixture of the following constituents: 40 to 90% of lactose; 8 to 50% of whey protein; 0.1 to 7% of milk fat; 0.1 to 10% of whey minerals and 0.1 to 5%of water (% = % by weight).
The stabiliser according to the main patent is sweet whey protein. It has now been found that not only sweet whey protein has a stabilising effect for lipase, but, quite generally, globular animal proteins.
The present invention provides an enzyme preparation containing a lipase of non-animal origin and, as stabiliser, 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding as stabiliser 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 109 of whey minerals and 0.1 to 5% of water (% = % by weight).
The invention also provides a pharmaceutical preparation containing a lipase of non-animal origin and from 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = % by weight).
The invention further provides processes for the production of the preparations defined above which comprises mixing the components.
Animal globular proteins include, for example: albumins (ov-albumin, lact-albumin, serum-albumin), globulins, prolamines and glutelins, globins, protamines, histones. Such proteins may be used individually or mixtures of these proteins may be used.
5 to 50 parts by weight, preferably 5 to 25 parts by weight of protein are used according to the invention for stabilising one part by weight of lipase. In particular, 10 to 20 parts by weight of albumin are used per part by weight of lipase.
Instead of the pure proteins, it is also possible to use protein preparations whose main constituent is an animal globular protein or protein mixture. Such preparations are commercially available and are obtained from natural protein sources by conventional methods of recovery and possible subsequent enrichment of the globular protein (cf.
Ullmanns Encyklopadie der technischen Chemie, third edition, volume 14, pages 409 to 431). Examples of such preparations include: whey protein preparations, plasma protein preparations, protein preparations of egg white.
With such preparations which contain other constituents, the quantity to be used is based exclusively on the quantity of the globular protein fraction.
Egg albumin is particularly preferred as the stabiliser according to the invention.
The preparations according to the invention may also contain 0.1 to 5 parts by weight, preferably 1 to 2 parts by weight (based on 1 part by weight of lipase) of minerals. Such minerals include, for example: phosphates, citrates, chlorides, sulphates, sodium carbonate, potassium carbonate, calcium carbonate. magnesium carbonate and also traces of iron carbonate. These salts may be present individually or as a mixture. If they are present in a mixture, the metals content in the salt mixture is for example, as follows, in percentages by weight: sodium 2 to 8, preferably 4 to 5% by weight, potassium 10 to 30, preferably 15 to 20% by weight; calcium 2 to 30, preferably 4 to 15% by weight; magnesium 0.5 to 3, preferably 0.8 to 1.5% by weight, iron 0.01 to 0.1, preferably 0.02 to 0.08% by weight.
Based on one part by weight of magnesium, the mixture contains, for example, 3 to 8, preferably 5 to 7 parts by weight of sodium, 2 to 15, preferably 4 to 8 parts by weight of calcium and 15 to 30, preferably 18 to 25 parts by weight of potassium. The acid content in percentages by weight in the salt mixture is, for example, as follows: phosphate anion (Po43-) 10 to 50, preferably 15 to 25% by weight; citrate anion 10 to 30, preferably 15 to 25% by weight; chloride anion 10 to 20, preferably 12 to 16% by weight; sulphate anion 2 to 8, preferably 3 to 6% by weight, carbonate anion 2 to 15, preferably 5 to 10% by weight; based on 1g of sulphate anion, the mixture contains, for example 2 to 5, preferably 2.5 to 3 parts by weight of chloride anion, 3 to 10, preferably 4 to 6 parts by weight of phosphate anion, 3 to 10, preferably 4 to 6 parts by weight of citrate anion and 0.5 to 2, preferably 0.8 to ].5 carbonate anion.
Based on 100 g weight of the preparations, the preparations generally contain 0.5 to 5 parts by weight, preferably 0.8 to 2. in particular 0.8 to 1.5 parts by weight of lipase of non-animal origin.
With regard to all other particulars, in particular those relating to lipase, other enzyme additives, conventional support and auxiliary materials and other additives the preparations according to the present invention are as described in the main patent. The same applies with regard to the production of the preparations.
The globular animal proteins described herein have the same stabilising effect as stated for sweet whey protein in the main patent, i.e. in particular an improvement in the durability of lipase when combined and/or mixed with conventionally used auxiliary and additive substances. in particular those with surface active properties such as aluminium hydroxide, aluminium hydroxide gel. aluminium oxide (see H.P. Fiedler, Lexikon der
Hilfstoffe fur Pharmazie, Kosmetik and angrenzende Gebiete, 1971, pages 43 and 44),
Aerosil, ("Aerosil" is a Registered Trade Mark), magnesium carbonate, aluminium salts (aluminium-trisilicates. aluminium phosphates).
The invention is illustrated by the following Examples.
Example 1
1 part by weight of lipase of non-animal origin is finally ground in a mortar and mixed (temperature 20"C) with 20 parts by weight of aluminium hydroxide gel (dried) and 13.5 parts of egg albumin.
If the albumin is omitted and replaced by 13.5 parts by weight of glucose. a loss of activity of about 409 is shown to have taken place after mixing in comparison to the mixture containing the egg albumin.
Example 2 (Tablet)
The tablet is composed of the following components:
Lipase S 60 from Rh izop us arrhizus 20 mg
Enzyme concentrate from Aspergillus orV-ae 100 mg
Dimethylpolysiloxane activated by silica gel 263 mg
Aluminium hydroxide gel 500 mg
Egg albumin 270 mg
Sucrose 515 mg
Saccharin-sodium 2.5 mg
Sorbitol 135 mg
Highly dispersed silica 44 mg
Talcum 60.5 mg
Vanilla 2.5 mg
Caramel flavouring 7.5 mg
1920.0 mg
The dimethylpolysiloxane is described, for example, in German Offenlegungsschrift No.
2,408,290 on page 1, last paragraph and page 2. The 263 mg of activated dimethylpolysiloxane specified above are composed of 250 mg of pure dimethylpolysiloxane and 13 mg of silica gel.
The silica gel used for activation is, for example, the silicon dioxide described in German
Offenlegungsschrift No. 2,408,290, page 3.
The term aluminium hydroxide gel includes pulverulent oxides, hydrated oxides, hydroxides and basic salts of aluminium containing not less than 40% of Al203 (see
Ullmanns Encyclopadie der technischen Chemie, third edition, volume 4, page 545-546 and volume 13, page 356). It includes, in particular, an aluminium hydroxide gel obtained in precipitation of aluminium salt solutions (for example sulphate solutions) with ammonium carbonate or sodium carbonate and drying of the filter cake. (Al203 content not less than 47%, preferably 50 to 60%). The pH of a 4% (weight/volume) suspension in CO2-free water should not exceed 10.0. Such aluminium hydroxide gels are marketed under the name "Teg".
The highly dispersed silica is a silica obtained by hydrolysis of silicon tetrachloride in the hydrogen flame (Aerosil). Such a silica has, for example, the following characteristics: specific surface area (m2/g) according to BET: 50 - 225, preferably 120 - 225 or 170 - 225; average size of the primary particles in millimicrons: 12 - 30, preferably 12- 16; Bulk density (standard product) in g/litre: about 60; bulking volume (standard product according to DIN 53 194) in ml/100 g; 1500 to 2000, preferably 1700 to 2000; pH-value (according to DIN 53 200) in 4% aqueous dispersion: 3.5 to 4.3, preferably 3.6 to 4.3.
The tablet is produced for example as follows: 1. Granulate
1) 25.75 kg of sucrose and
50.0 kg of dried aluminium hydroxide gel are sieved (mesh width approximately 1.2 mm) and mixed in a suitable mixer (forced circulation mixer, for example a Diosna-mixer, the word "Diosna" being a Registered Trade Mark).
= Mixture 1/1 2) 26.3 kg of dimethylpolysiloxane activated with silica gel are added to and intensively mixed with mixture I/1
= Mixture 1/2
3) Granulation 25.75 kg of sucrose are dissolved in 12.0 kg of demineralised water at +80 C with stirring.
= Solution 1
0.25 kg of saccharin-sodium are dissolved in 0.85 kg of demineralised water with stirring.
= Solution 2
Solution 1 is allowed to cool to room temperature before further processing. Solution 2 is then introduced into solution 1 with stirring.
= Sugar solution
Mixture 1/2 is moistened with the sugar solution and intensively compounded in a suitable mixer (for example Diosna).
About 0.95 kg of demineralised water are then added. The quantity of water and mixing time must be such that a uniformly moistened mass is formed. The moist mass is passed through a granulating machine (3 to 4 mm) and dried at 60 to 650C.
The dry coarse-grained mass is passed through a 1.2 mm mesh sieve.
= Granulate for the enzyme
chewing tablets
Maximum relative moisture content of the dried granulate: 10%
II. Production of the enzyme pressing composition for 80,000 tablets
1) 1.05 kg talcum
0.05 kg highly dispersed silica
0.25 kg vanilla
0.75 kg caramel flavouring
2.10 kg are sieved (mesh width 0.5 mm) and subsequently mixed in a suitable mixer.
= Mixture III1 2) 27.0 kg egg albumin
5.0 kg talcum
4.35 kg highly dipsersed silica
36.35 kg are mixed in a mixer (for example Rotex) and passed through an Express sieve (mesh width 1.0mum).
= Mixture 11/2
3) 2.0 kg. fungus lipase from Rhizopus arrhizus
10.0kg enzyme concentrate from Aspergillus oryzae
2.10 kg mixture II/1 14.10 kg
are combined with about 10 kg of mixture II/2 and are passed through an Express sieve
(mesh width 1.0 mm). About 5 kg of mixture II/2 are again passed through the Express
sieve used.
= Mixture 11/3 = 29.10 kg
4) 29.20 kg mixture II/3 21.35 kg mixture II/2 (=residue)
50.45 kg
are mixed in a suitable mixer (for example Diosna).
= Mixture 11/4
5) 13.75 kg of sorbitol are passed through a 1.2 mm mesh sieve and dried for about 5 hours at 600C. Relative moisture content of the dried sorbitol: 15% (+ 5%).
6) 50.45 kg mixture II/4 14.5 kg dried sorbitol
128.05 kg of granulate for enzyme chewing tablets
192.00 kg are mixed in a suitable mixer (for example Turbula: Turbula drum about 370 litres capacity, 1 hour at 10 r.p.m.
= Composition ready
for pressing
Maximum relatively moisture content of the pressing composition: 22%
Bulk volume: 100 g = approximately 140 ml.
III. Pressing Operation
Tablets weighing 2.4 g are produced from the pressing composition in an eccentric or rotary press.
WHAT WE CLAIM IS:
1. An enzyme preparation containing lipase of non-animal origin and, as stabiliser 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding as stabiliser 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (u = ] by weight).
2. A preparation as claimed in claim 1, wherein the stabiliser is egg albumin.
3. A process for the production of a lipase-containing enzyme preparation with improved activity which comprises mixing the lipase of non-animal origin with to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = % by weight).
4. A process as claimed in claim 3, wherein at least one conventional auxiliary and/or support substance is included.
5. A process as claimed in claim 3 or 4, wherein the stabiliser is egg albumin.
6. A pharmaceutical preparation containing a lipase of non-animal origin and from 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = % by weight).
7. A preparation as claimed in claim 6, wherein the stabiliser is egg albumin.
8. A preparation as claimed in claim 6 or 7, which additionally contains a proteinase and/or an amylase.
9. A preparation as claimed in claim 8, containing an enzyme concentrate of Aspergillus orvzae.
io. A preparation as claimed in any of claims 6 to 9 which is intended for oral administration.
11. A preparation as claimed in claim 10, in the form of tablets.
12. A preparation as claimed in claim 11, in the form of chewing tablets.
13. A process for the production of a pharmaceutcial preparation which comprises mixing a lipase of non-animal origin with 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = % by weight).
14. A process as claimed in claim 13, wherein at least one other pharmaceutical auxiliary and/or additive is included.
15. A process as claimed in claim 13 or 14, wherein the mixture obtained is pressed into tablets.
16. A process as claimed in claim 15, wherein the stabiliser is egg albumin.
17. An enzyme preparation containing a lipase substantially as described with particular reference to either of the Examples.
18. A process for the preparation of an enzyme preparation containing a lipase
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (19)
- **WARNING** start of CLMS field may overlap end of DESC **.5) 13.75 kg of sorbitol are passed through a 1.2 mm mesh sieve and dried for about 5 hours at 600C. Relative moisture content of the dried sorbitol: 15% (+ 5%).6) 50.45 kg mixture II/4 14.5 kg dried sorbitol 128.05 kg of granulate for enzyme chewing tablets 192.00 kg are mixed in a suitable mixer (for example Turbula: Turbula drum about 370 litres capacity, 1 hour at 10 r.p.m.= Composition ready for pressing Maximum relatively moisture content of the pressing composition: 22% Bulk volume: 100 g = approximately 140 ml.III. Pressing Operation Tablets weighing 2.4 g are produced from the pressing composition in an eccentric or rotary press.WHAT WE CLAIM IS: 1. An enzyme preparation containing lipase of non-animal origin and, as stabiliser 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding as stabiliser 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (u = ] by weight).
- 2. A preparation as claimed in claim 1, wherein the stabiliser is egg albumin.
- 3. A process for the production of a lipase-containing enzyme preparation with improved activity which comprises mixing the lipase of non-animal origin with to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = % by weight).
- 4. A process as claimed in claim 3, wherein at least one conventional auxiliary and/or support substance is included.
- 5. A process as claimed in claim 3 or 4, wherein the stabiliser is egg albumin.
- 6. A pharmaceutical preparation containing a lipase of non-animal origin and from 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = % by weight).
- 7. A preparation as claimed in claim 6, wherein the stabiliser is egg albumin.
- 8. A preparation as claimed in claim 6 or 7, which additionally contains a proteinase and/or an amylase.
- 9. A preparation as claimed in claim 8, containing an enzyme concentrate of Aspergillus orvzae.
- io. A preparation as claimed in any of claims 6 to 9 which is intended for oral administration.
- 11. A preparation as claimed in claim 10, in the form of tablets.
- 12. A preparation as claimed in claim 11, in the form of chewing tablets.
- 13. A process for the production of a pharmaceutcial preparation which comprises mixing a lipase of non-animal origin with 5 to 50 parts by weight (based on 1 part by weight of lipase) of an animal globular protein or protein mixture, excluding 10 to 50 parts by weight of a mixture composed of 40 to 90% of lactose, 8 to 50% of whey protein, 0.1 to 7% of milk fat, 0.1 to 10% of whey minerals and 0.1 to 5% of water (% = % by weight).
- 14. A process as claimed in claim 13, wherein at least one other pharmaceutical auxiliary and/or additive is included.
- 15. A process as claimed in claim 13 or 14, wherein the mixture obtained is pressed into tablets.
- 16. A process as claimed in claim 15, wherein the stabiliser is egg albumin.
- 17. An enzyme preparation containing a lipase substantially as described with particular reference to either of the Examples.
- 18. A process for the preparation of an enzyme preparation containing a lipasesubstantially as described with particular reference to either of the Examples.
- 19. An enzyme preparation when produced by a process as claimed in any of claims 3 to 5, 13 to 16 or 18.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB728578A GB1574269A (en) | 1978-02-23 | 1978-02-23 | Non-animal lipase preparations having activity |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB728578A GB1574269A (en) | 1978-02-23 | 1978-02-23 | Non-animal lipase preparations having activity |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1574269A true GB1574269A (en) | 1980-09-03 |
Family
ID=9830163
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB728578A Expired GB1574269A (en) | 1978-02-23 | 1978-02-23 | Non-animal lipase preparations having activity |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB1574269A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0068594A1 (en) * | 1981-07-01 | 1983-01-05 | Nederlandse Organisatie voor toegepast-natuurwetenschappelijk onderzoek TNO | Process for carrying out an enzymatic reaction |
AT401652B (en) * | 1993-08-19 | 1996-11-25 | Chemie Linz Gmbh | METHOD FOR INCREASING THE ACTIVITY OF LIPASES |
WO2006056469A1 (en) * | 2004-11-29 | 2006-06-01 | Basf Aktiengesellschaft | Enzyme formulations |
EP2085469A1 (en) * | 2008-01-30 | 2009-08-05 | BAM Bundesanstalt für Materialforschung und -prüfung | Lipase formulation |
-
1978
- 1978-02-23 GB GB728578A patent/GB1574269A/en not_active Expired
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0068594A1 (en) * | 1981-07-01 | 1983-01-05 | Nederlandse Organisatie voor toegepast-natuurwetenschappelijk onderzoek TNO | Process for carrying out an enzymatic reaction |
AT401652B (en) * | 1993-08-19 | 1996-11-25 | Chemie Linz Gmbh | METHOD FOR INCREASING THE ACTIVITY OF LIPASES |
WO2006056469A1 (en) * | 2004-11-29 | 2006-06-01 | Basf Aktiengesellschaft | Enzyme formulations |
EP2085469A1 (en) * | 2008-01-30 | 2009-08-05 | BAM Bundesanstalt für Materialforschung und -prüfung | Lipase formulation |
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Legal Events
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---|---|---|---|
PS | Patent sealed | ||
PCNP | Patent ceased through non-payment of renewal fee |