GB1574707A – Stabilisation of compounds
– Google Patents
GB1574707A – Stabilisation of compounds
– Google Patents
Stabilisation of compounds
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Publication number
GB1574707A
GB1574707A
GB1021/76A
GB102176A
GB1574707A
GB 1574707 A
GB1574707 A
GB 1574707A
GB 1021/76 A
GB1021/76 A
GB 1021/76A
GB 102176 A
GB102176 A
GB 102176A
GB 1574707 A
GB1574707 A
GB 1574707A
Authority
GB
United Kingdom
Prior art keywords
stabiliser
process according
film
compound
thickness
Prior art date
1976-01-12
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.)
Expired
Application number
GB1021/76A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Unilever PLC
Original Assignee
Unilever PLC
Priority date (The priority date 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 date listed.)
1976-01-12
Filing date
1976-01-12
Publication date
1980-09-10
1976-01-12
Application filed by Unilever PLC
filed
Critical
Unilever PLC
1976-01-12
Priority to GB1021/76A
priority
Critical
patent/GB1574707A/en
1977-01-06
Priority to FI770035A
priority
patent/FI770035A/fi
1977-01-06
Priority to NZ182997A
priority
patent/NZ182997A/en
1977-01-10
Priority to NL7700158A
priority
patent/NL7700158A/en
1977-01-10
Priority to AU21187/77A
priority
patent/AU513804B2/en
1977-01-10
Priority to ZA00770108A
priority
patent/ZA77108B/en
1977-01-11
Priority to IE45/77A
priority
patent/IE45084B1/en
1977-01-11
Priority to DK9277A
priority
patent/DK148713C/en
1977-01-11
Priority to FR7700619A
priority
patent/FR2337755A1/en
1977-01-11
Priority to IT19160/77A
priority
patent/IT1113502B/en
1977-01-11
Priority to JP185777A
priority
patent/JPS52154581A/en
1977-01-11
Priority to SE7700228A
priority
patent/SE7700228L/en
1977-01-11
Priority to BE173990A
priority
patent/BE850275A/en
1977-01-11
Priority to CA269,477A
priority
patent/CA1108037A/en
1977-01-11
Priority to IN24/CAL/77A
priority
patent/IN145036B/en
1977-01-11
Priority to NO770095A
priority
patent/NO770095L/en
1977-01-12
Priority to BR7700203A
priority
patent/BR7700203A/en
1977-01-12
Priority to DE2759342A
priority
patent/DE2759342C3/en
1977-01-12
Priority to DE19777700749U
priority
patent/DE7700749U1/en
1977-01-12
Priority to DE2701063A
priority
patent/DE2701063B2/en
1977-01-12
Priority to LU76551A
priority
patent/LU76551A1/xx
1980-09-10
Publication of GB1574707A
publication
Critical
patent/GB1574707A/en
1987-11-23
Priority to US07/124,351
priority
patent/US4935347A/en
Status
Expired
legal-status
Critical
Current
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Classifications
C—CHEMISTRY; METALLURGY
C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
C12Q1/18—Testing for antimicrobial activity of a material
B—PERFORMING OPERATIONS; TRANSPORTING
B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
C—CHEMISTRY; METALLURGY
C07—ORGANIC CHEMISTRY
C07G—COMPOUNDS OF UNKNOWN CONSTITUTION
C07G11/00—Antibiotics
B—PERFORMING OPERATIONS; TRANSPORTING
B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
B01L2200/12—Specific details about manufacturing devices
B—PERFORMING OPERATIONS; TRANSPORTING
B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
B01L2200/16—Reagents, handling or storing thereof
Description
PATENT SPECIFICATION
( 11) 1 574 707 Application No 1021/76 ( 22) Filed 12 Jan 1976
Complete Specification Filed 11 Jan 1977
Complete Specification Published 10 Sep 1980
INT Cl 3 C 12 Q 1/00 ( 52) Index at acceptance G 1 B BW CB ( 71) Inventor: Michael Herder Coleman ( 54) STABILISTATION OF COMPOUNDS ( 71) We, UNILEVER LIMITED, a company organised under the laws of Great Britain, of Unilever House, Blackfriars, London E/C 4, England, do hereby declare the invention for which we pray that a patent may be particularly described in and by the following statement:-
The invention relates to a method for stabilising compounds, particularly biologically active compounds, and to a device useful for the application of said method and for performing biological tests.
It is commonly necessary for the identification of microorganisms to determine the effects of a variety of biologically active substances upon their growth This is of particular importance in the case of antibiotic substances, where knowledge of the amount necessary to inhibit growth is needed for therapeutic application The classical method for determining this minimum inhibitory concentration (MIC) is to prepare a series of tubes containing a liquid culture medium, with a different amount of antibiotic in each tube After inoculation with the microorganism, and incubation the MIC can be determined from the tube with a lower antbiotic concentration, in which no growth has occured.
Alternative methods involve either preparing agar plates containing a series of antibiotic concentrations or plain agar plates into which the antibiotics are allowed to diffuse from paper discs impregnated with the antibiotics.
All three methods require skill and considerable effort to perform and since some antibiotics are not stable in the culture medium the media require to be prepared freshly before use.
Various methods have been proposed for reducing the effort of performing antibiotic sensitivity tests.
US specification 3,416,998 describes a process according to which several test compounds such as chemotherapeutical agents are mixed with a 1 5 % aqueous solution of agar The obtained mixture is poured on a plate 45 to form a relatively thick layer which is then dried The dried layers can be divided into smaller pieces containing a constant quantity of material per unit area of layer Small discs of this meterial maybe applied on bacterial 50 cultures and the active agent is allowed to diffuse into the culture medium The influence of the compound used on the growth of bacteria can subsequently be assessed This method is however cumbersome and the results tend to 55 vary considerably 1 Dutch patent application 6917655 describes a method for assessing the growth and the physiology of bacteria by incorporating a chemical compound such as amino acids or 60 other compounds which promote the growth of bacteria, into a solution of an inert high molecular material and adding this mixture in different tubes to obtain layers of material In a later stage an inoculum is added and the 65 growth is subsequently assessed An aqueous solution of agar or a 1 % solution of polyacrylamide are recommended as stabilisers for the chemical compound.
A disadvantage of the above method is that 70 the deposited layer of chemical compound incorporated in the stabiliser is rather thick and has an insufficient mechanical stability.
Another disadvantage is that a fairly big amount of stabiliser is used In some instances 75 this big proportion of stabiliser influences the composition and properties of the liquid in the tube.
The method involving the use of paper discs impregnated with antibiotics is the subject of 80 Dutch patent application 7205619 which involves the use of a paper disc as a carrier which is impregnated with an antibiotic which is placed on an agar plate The antibiotic diffuses from the paper on the agar and pro 85 duces a concentration gradient Standardisation of this method gives problems and the obtained results vary considerably from one operator r ( 21) ( 23) ( 44) kt ( 51) 1 574 707 to another.
French Patent specification 1,488,866 and
Dutch patent application 7211868 describe a device for the determination of sensitivity of microorganisms in the presence of different antibiotics The chemical compounds and the organism to be tested are present in lyophilised form which renders them sensitive to mechanical loss and leads to unreliable results.
There is thus a need for a simple economical and efficient method for stabilising very small quantities of accurarately predispensed amounts of particularly biologically active substances in both mechanically and chemically 15stable form.
We have found a method for stabilising small amounts of biologically active substances which obviates to a great extent many of the difficulties previously encountered in the preparation of suitable systems for the determination of their effects on bacterial growth and which is compatible with known requirements for the satisfactory culture of microorganisms.
The process for stabilising compounds according to the invention involves:
a) preparing a mixture comprising at least one component to be stabilised, a film-forming stabiliser and a solvent; b) dispensing a small proportion of the mixture upon a solid surface; and c) allowing the solvent to evaporate to give a coherent,dried film adhering to said solid surface and having a thickness not exceeding 50 microns.
By stabilisation is meant throughout the specification both a mechanical stabilisation and a chemical stabilisation for example against hydrolysis, p H and ionic environment variations, high temperature.
The compound to be stabilised can be any compound, particulary biologically active compounds, such as antibiotics, which are sensitive to heat, presence of moisture, extreme p H conditions.
As stabiliser a wide range of materials with film-forming properties, can be used, such as agar, cellulosic derivatives or preferably proteinaceous materials like gelatin, casein, bovine serum albumine For medical purposes gelatin is preferably used because a) it is an ampholyte with a good buffering capacity; b) it is reasonably soluble in relatively cold solution, which is a big advantage when thermolabile compounds are to be incorporated therein; c) it is a generally accepted microbiological medium; d) it is a good film-forming material.
The solvent to be used can in principal be any solvent.
For medical purposes distilled water is generally preferred for preparing aqueous solutions of the stabiliser and the compound to be stabilised The preparation ‘of such solutions and all subsequent steps are preferably carried out below the temperature at which any of the components of the mixture The volume and concentration of the portions of the mixture of stabiliser and compound to be stabilised are chosen such that the material deposited in the solid surface yields after drying films of thickness not exceeding 50microns Suitable volumes and concentrations can easily be determined in each particular case to meet the requirements regarding thickness of the film, coherence and adherence to the solid surface 80 Useful solutions of the stabiliser e g gelatin contain the stabiliser in a concentration which usually lies between 0 001 and 0 5 % w/v, preferably between 0 01 and 0 1 % w/v and particularly between 0 01 and 0 03 % w/v 85 When using a device as described further in the specification, volumes of 1 to 500 microliters, preferably 10 to 100 microliters of a solution of the mixture of stabiliser and compound to be stabilised are dispensed on the 90 solid surface.
The solution to be dispensed is usually prepared by mixing appropriate volumes of the solutions of stabiliser and compound to be stabilised, if necessary adjusting the p H to 95 the desired value, and where necessary, sterilising.
In order to achieve the necessary mechanical stability i e good adherence to the solid surface after drying the films need to have a thickness 100 from 0 01 to 50 microns, preferably from 0 01 to 5 microns, and ideally from 0 3 to 1 micron.
It is important that the dried films are of a thickness within the given range, since contraction of thicker films during drying causes 105 detachment at the edges and loss of mechanical stability.
To some extent the adherence of the films depends on the geometry of the solid surface on which the mixture is dispensed 110 There seems little or no difference in the behaviour of the obtained thin films towards different synthetic plastic materials such as polyethylene, polystyrene, polycarbonate, polyvinylchloride, polymethacrylate or poly 115 tetrafluorethylene.
The drying procedure requires also spme,.
attention Useful dried films are formed by removing the solvent which can be any solvent but is usually water, by airdrying or preferably 120 under reduced pressure It is preferred that the drying is carried out under such conditions that the liquid does not boil or freeze since boiling can give rise to mechanical loss, and freeze-drying does not yield a coherent film 125 In the case of water as a solvent, the liquid is preferably kept between 5 and 300 C and the vacuum around 20 Torr.
A very useful application of the above described method of stabilising compounds 130 1 574707 is the production of a device useful for performing biological tests, particularly the determination of the minimum inhibitory concentration of antibiotics against pathogenic microorganism A useful device to be used for such determinations consists of an array of rows of wells formed in a plate, the wells containing a coherent, dry film, made by the process of the present invention, of a thickness from 0 01 ‘ to 50 r microns, of at least one compound stabilised by incorporation in a film-forming stabiliser, adhering to the inner surface of the wells.
The compound to be stabilised can be any L 5 compound, especially a biological active compound such as an antibiotic.
The stabiliser can be any film-forming substance When used for medical purposes a proteinaceous material such as gelatin or bovine z 2: albumine is preferred.
The wells can contain the same or different compounds, in the same concentration or in predetermined concentrations varying from well to well.
The films are prepared following the procedure described above The device can be sealed with an adhering foil and may be stored at ambient temperatures for several months until required for use.
The device can be made of any material A synthetic material like polystyrene is particularly suitable.
A preferred embodiment of the device according to the invention will now be des3.5 cribed’ with reference to the accompanying drawings in which:
Figure 1 is a plan view of the device; and Figure 2 is a cross-sectional view along the line 1 I-11 in Figure 1.
4 o) The device shown in Figure 1 consists of a rectangular plate 3 of approximately 12 x 8 x 1.5 cm, containing an array of 8 rows of 12 circular wells 4, 0 5 in diameter and 1 cm deep, having hemispherical bottoms (see Figure 2).
4 S Dilutions of any chemical compound to be tested in solution with the stabiliser are dispensed in the first 10 well of the row, the last 2 wells receiving aliquots of the stabilising solution only The volume, concentration of 550 the stabiliser and the chemical compound and the surface area on which the solution is dispensed are chosen such that after drying films of a thickness from 0 01 to 50 microns, preferably from 0 01 to 5 microns and ideally from 03 to 1 micron, are formed e g on the bottom of the wells.
After addition of the mixture of stabiliser and the chemical compound to be tested and drying by air or vacuum drying the device can be covered with an adhering foil or laminate and, sealed, to protect it from its environment.
The above illustrates the use of the invention for stabilising biologically active’ compounds It is understood that the invention covers stabilising any substance if necessary by applying obvious variations of the above method.
The invention will be further illustrated by the following Examples.
EXAMPLE I 70
Solutions of the antibiotics listed, to the concentration indicated, were prepared in distilled water at room temperature:
Sulphamethoxazole 200 ug/ml Trimethoprim 40 ug/mi 75 Benzyl penicillin 12 ug/m I Ampicillin 80 ug/ml Cephaloridine 80 ug/mni Tetracycline 80 ug/ml Erythromycin 80 ug/mi 80 Gentamicin 80 ug/ml The solutions were sterilised in the cold by passing through a suitable filter, and each was diluted with an equal volume of a 0 05 % w/v solution of good grade gelatin ( 200 bloom 85 number) in distilled water at room temperature, which had previously been adjusted to p H 7 and sterilised in an autoclave for 15 minutes at 15 lbs pressure From each such antibiotic solution a further series of nine doubling dilutions were 90 prepared aseptically, by successive dilutions with equal volumes of a 0 025 %o w/v solution of gelatin, previously adjusted to p H 7 and sterilised by autoclaving.
These solutions were then transferred to the 95 sterile reservoirs of a device (U K Patent Specification No 1 520 745) capable of dispensing 96 drops, each of 25 ul volume, into the wells of a polystyrene plate The plates used were rectangular in shape approximately 12 x 8 100 x 1 5 cm; each containing an array of 8 rows of 12 circular wells, 0 5 cm in diameter and 1 cm deep having hemispherical bottoms ‘ The dilutions of each antibiotic were dispensed into the first 10 wells of a row, the last two wells 105 receiving 25 ul aliquots of 0 025 % w/v gelatin solution only.
The plates so prepared were vacuum-dried by ensuring that the vaccum did not fall below Torr, nor the temperature rise substantially 110 above ambient temperature The thickness of the obtained films was about 0 4 microns The plates were sealed, with a laminate of aluminium foil in a heat sealing device (from Sharp-lntermatic of Aylesham, U K) 115 Plates so prepared were examined for antibiotic potencies by the addition of a 50 ul aliquot of a suitable bacteriological culture broth, containing approximately 106 microorganisms per ml Various culture broths have 120 been employed, but the one principally used is the heart-infusions broth (from Difco Laboratories of Detroit, U S) Two microorganisms have been used in most of the tests, Staph.
aureus NCTC 6572 and E coli NCTC 10418 125 The plates were then resealed with a suitable adhesive film (from Cellotape Products UK of Middlesex, U K) and incubated at 370 C overnight The minimum inhibitory concentration (MIC) of each of the antibodies was then 130 1 574 707 determined by inspection of the plates, and noting the lowest concentration at which was apparent Growth was indicated by a button of cells at the bottom of the wells For control purposes the penultimate well of each row received a 50 microliter aliquot of the culture broth without organisms, and should remain free of growth after incubation; whilst the last well of each row, having received an inoculum of organisms, but no antibiotic substance should give good growth throughout No defeats in the procedure have been indicated by these two control columns in any of the plates examined.
No loss of potency in the antibiotics tested has been observed over a period of 3 months whether stored at -200 C, 2 f C or C, whereas the penicillins in particular show a rapid loss of potency when dried without the stabiliser, and stored at ambient temperatures.
EXAMPLE II
The procedure of Example I was followed with the exception that 25 ul of an aqueous solution of 0 075 % w/v of gelatin was used.
The thickness of the obtained film was about one micron.
EXAMPLE III
The procedure of Example I was followed with the exception that 25 ul of an aqueous solution of 0 0075 % w/v gelatin was used.
The thickness of the film obtained was about 0.1 micron.
EXAMPLE IV
The procedure of Example I was followed with the exception that 25 ul of an aqueous solution 0 025 % w/v bovine serum albumine was used The thickness of the film obtained was about 0 4 microns.
The product obtained according to Examples 2 4 displayed the same outstanding properties as the product according to Example 1.
Claims (1)
WHAT WE CLAIM IS:
1 A process for stabilising compounds, which comprises:
a) preparing a mixture comprising at least one compound to be stabilised, a film-forming stabiliser and a solvent; b) dispensing a small portion of the mixture upon a solid surface; and c) allowing the solvent to evaporate to leave on the solid surface a quantity of material in the form of a coherent, dired film adhering to said solid surface and having a thickness from 0.01 to 50 microns.
2 A process according to claim 1, in which the compound to be stabilised is a biologically active compound.
3 A process according to claim 1, in which the compound to be stabilised is an antibiotic.
4 A process according to claim 1, in which the stabiliser is a filmforming proteinaceous material 65 A process according to claim 4, in which the stabiliser is gelatin.
6 A process according to claim 4, in which the stabiliser is bovine serum albumine.
7 A process according to claim 1, in 70 which the solvent is water.
8 A process according to claim 1, in which a portion of 1 to 500 microliters of a mixture containing 0 001 to 0 5 % w/v of stabiliser is dispensed on the solid surface 75 9 A process according to claim 8, in which 10 to 100 microliters of a mixture containing 0 01 to 0 1 % w/v stabiliser are dispensed on the solid surface.
A process according to claim 1, in 80 which the thickness of the film is from 0.01 to 5 microns.
11 A process according to claim 1, in which the thickness of the film is from 0 3 to 1 micron 85 12 A process according to claim 1, wherein the mixture dispensed on the solid surface is dried under such conditions that the mixture does not boil or freeze.
13 A process accordng to claim 12, in 90 which the drying is carried out under reduced pressure.
14 A process accordng to claim 12, in which air-drying is applied.
Apparatus consisting of an array of 95 rows of wells formed in a plate, the wells containing a coherent, dry film made by process of claim 1, of a thickness from 0 01 to microns of at least one compound stabilised by incorporation in a film-forming 100 stabiliser, adhering to the inner surface of the wells.
16 Apparatus according to claim 15, in which the thickness of the films varies from 0.01 to 5 micron.
17 Apparatus according to claim 16, in which the thickness of the film varies from 0.3 to 1 micron.
18 Apparatus according to claim 15, wherein the stabiliser is a proteinaceous substance.
19 Apparatus according to claim 18, wherein the stabiliser is gelatin.
Apparatus according to claim 18, wherein the stabiliser is bovine serum albumine.
21 Apparatus according to claim 15, wherein the compound to be stabilised is an antibiotic.
22 Apparatus according to claim 15, in which the wells contain films containing the same or different compounds present in the same or in predetermined concentrations varying from well to well.
23 Apparatus according to claim 15 covered by an adhering foil.
24 Apparatus according to claim 15 as hereinbefore described with particular 1 574 707 5 reference to Example I.
J E Rogers Chartered Patent Agent Printed for Her Majesty’s Stationery Office by MULTIPLEX techniques ltd, St Mary Cray, Kent 1980 Published at the Patent Office, 25 Southampton Buildings, London WC 2 l AY, from which copies may be obtained.
GB1021/76A
1976-01-12
1976-01-12
Stabilisation of compounds
Expired
GB1574707A
(en)
Priority Applications (22)
Application Number
Priority Date
Filing Date
Title
GB1021/76A
GB1574707A
(en)
1976-01-12
1976-01-12
Stabilisation of compounds
FI770035A
FI770035A
(en)
1976-01-12
1977-01-06
NZ182997A
NZ182997A
(en)
1976-01-12
1977-01-06
Stabilising biologically active compounds,and apparatus for performing tests
NL7700158A
NL7700158A
(en)
1976-01-12
1977-01-10
METHOD OF STABILIZING CONNECTIONS AND A DEVICE CONTAINING CONNECTIONS IN STABILIZED FORM.
AU21187/77A
AU513804B2
(en)
1976-01-12
1977-01-10
Process for producing apparatus for carrying out tests involving biologically active compounds, and apparatus so produced
ZA00770108A
ZA77108B
(en)
1976-01-12
1977-01-10
Stabilisation of compounds
SE7700228A
SE7700228L
(en)
1976-01-12
1977-01-11
STABILIZATION OF ASSOCIATIONS
NO770095A
NO770095L
(en)
1976-01-12
1977-01-11
PROCEDURES FOR STABILIZATION OF COMPOUNDS, ESPECIALLY BIOLOGICAL ACTIVE CONNECTIONS, AND DEVICES FOR CARRYING OUT PROCEDURES.
FR7700619A
FR2337755A1
(en)
1976-01-12
1977-01-11
STABILIZATION OF BIOLOGICALLY ACTIVE COMPOUNDS
IT19160/77A
IT1113502B
(en)
1976-01-12
1977-01-11
PROCEDURE FOR THE STABILIZATION OF COMPOUNDS, PARTICULARLY OF ANTIBIOTICS USED IN BIOLOGICAL TESTS, AND DEVICE OBTAINED WITH THE PROCEDURE
JP185777A
JPS52154581A
(en)
1976-01-12
1977-01-11
Stabilization of compound
IE45/77A
IE45084B1
(en)
1976-01-12
1977-01-11
Stabilisation of compounds
BE173990A
BE850275A
(en)
1976-01-12
1977-01-11
STABILIZATION OF COMPOUNDS
CA269,477A
CA1108037A
(en)
1976-01-12
1977-01-11
Stabilisation of compounds
IN24/CAL/77A
IN145036B
(en)
1976-01-12
1977-01-11
DK9277A
DK148713C
(en)
1976-01-12
1977-01-11
APPARATUS FOR CULTIVATING MICRO-ORGANISMS ON A LIQUID SUBSTRATE AND PROCEDURE FOR ITS PREPARATION
BR7700203A
BR7700203A
(en)
1976-01-12
1977-01-12
PROCESS TO STABILIZE COMPOUNDS AND APPARATUS TO PERFORM BIOLOGICAL TESTS
DE2759342A
DE2759342C3
(en)
1976-01-12
1977-01-12
Device for mechanical and chemical stabilization of biologically active compounds with a film-forming stabilizer and for carrying out biological tests
DE19777700749U
DE7700749U1
(en)
1976-01-12
1977-01-12
DEVICE FOR PERFORMING CHEMICAL OR BIOLOGICAL TESTS
DE2701063A
DE2701063B2
(en)
1976-01-12
1977-01-12
Mechanical and chemical stabilization of biologically active compounds
LU76551A
LU76551A1
(en)
1976-01-12
1977-01-12
US07/124,351
US4935347A
(en)
1976-01-12
1987-11-23
Stabilization of compounds
Applications Claiming Priority (1)
Application Number
Priority Date
Filing Date
Title
GB1021/76A
GB1574707A
(en)
1976-01-12
1976-01-12
Stabilisation of compounds
Publications (1)
Publication Number
Publication Date
GB1574707A
true
GB1574707A
(en)
1980-09-10
Family
ID=9714767
Family Applications (1)
Application Number
Title
Priority Date
Filing Date
GB1021/76A
Expired
GB1574707A
(en)
1976-01-12
1976-01-12
Stabilisation of compounds
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US
(1)
US4935347A
(en)
JP
(1)
JPS52154581A
(en)
AU
(1)
AU513804B2
(en)
BE
(1)
BE850275A
(en)
BR
(1)
BR7700203A
(en)
CA
(1)
CA1108037A
(en)
DE
(3)
DE2759342C3
(en)
DK
(1)
DK148713C
(en)
FI
(1)
FI770035A
(en)
FR
(1)
FR2337755A1
(en)
GB
(1)
GB1574707A
(en)
IE
(1)
IE45084B1
(en)
IN
(1)
IN145036B
(en)
IT
(1)
IT1113502B
(en)
LU
(1)
LU76551A1
(en)
NL
(1)
NL7700158A
(en)
NO
(1)
NO770095L
(en)
NZ
(1)
NZ182997A
(en)
SE
(1)
SE7700228L
(en)
ZA
(1)
ZA77108B
(en)
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Assignee
Title
GB2165216A
(en)
*
1982-10-08
1986-04-09
Analytichem Int Inc
Disposable sample cassette for high pressure chromatography
US5079144A
(en)
*
1982-04-14
1992-01-07
Radiometer Corporate Development Ltd.
Microorganism testing with a hydrolyzable fluorogenic substrate
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Assignee
Title
JPS58179499A
(en)
*
1982-04-13
1983-10-20
Wako Pure Chem Ind Ltd
Stabilization of disc for bacterial sensitivity test
JPS6196999A
(en)
*
1984-10-18
1986-05-15
Kobayashi Seiyaku Kk
Method of testing sensitivity of bacteria to medicine
JPS6437404U
(en)
*
1987-08-31
1989-03-07
JPH0226901A
(en)
*
1988-07-13
1990-01-29
Kazuo Akagi
Stocking for slim body
DE4022792A1
(en)
*
1990-07-18
1992-02-06
Max Planck Gesellschaft
PLATE WITH AT LEAST ONE RECESS FOR RECEIVING CHEMICAL AND / OR BIOCHEMICAL AND / OR MICROBIOLOGICAL SUBSTANCES AND METHOD FOR PRODUCING THE PLATE
DE4116108A1
(en)
*
1991-05-17
1992-11-19
Behringwerke Ag
REAGENT FOR DETERMINING ION STRENGTH AND OF THE SPECIFIC WEIGHT OF AQUEOUS LIQUIDS AND METHOD
DE4209064C2
(en)
*
1992-03-20
1995-07-27
Gerhard Dr Noss
Method for supplying washing liquid to small, transparent test fields coated with cell cultures and for sucking off the washing liquid from the test fields
US5716798A
(en)
*
1992-09-22
1998-02-10
Becton Dickinson And Company
Enhanced detection of microorganisms in samples
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(en)
*
1994-05-11
1995-11-16
A I D Autoimmun Diagnostika Gm
Carrier for microscopy is multi-well plate with thin base to wells
DE4424112A1
(en)
*
1994-07-08
1996-01-11
Raytest Isotopenmesgeraete Gmb
Process for the production of a sample carrier
DE4446698C2
(en)
*
1994-12-14
1998-07-23
Medac Klinische Spezialpraep
Microtiter plate with a means for indicating the filling status, production of a microtiter plate and use of a pH indicator
JP2021519091A
(en)
2018-03-27
2021-08-10
セルックス・ダイアグノスティクス・インコーポレイテッド
Systems, methods and interfaces for parallel processing of antimicrobial susceptibility testing using different samples
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1935-11-05
Copeman Lab Co
Protective coatings and process of applying and removing
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1966-11-03
Ichthyol Ges
Process for the production of enzyme bodies for the implementation of enzymatic reactions
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1966-11-22
1973-11-22
Boehringer Mannheim Gmbh, 6800 Mannheim
Diagnostic means for the detection of the constituents of body fluids
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1967-10-11
1968-12-17
Research Corp
Method of detecting or classifying microorganisms using agar reagent sheets
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1970-10-19
1973-01-30
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Device and method for testing potency of biological control reagents
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1971-07-19
1973-01-18
Hoffmann La Roche
PACKAGING FOR BACTERIAL SAMPLES
CH571573A5
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*
1971-09-02
1976-01-15
Hoffmann La Roche
JPS5218272B2
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*
1972-01-27
1977-05-20
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1974-03-13
1976-08-17
Marine Colloids, Inc.
Applying reagent to medium and device therefor
1976
1976-01-12
GB
GB1021/76A
patent/GB1574707A/en
not_active
Expired
1977
1977-01-06
NZ
NZ182997A
patent/NZ182997A/en
unknown
1977-01-06
FI
FI770035A
patent/FI770035A/fi
not_active
Application Discontinuation
1977-01-10
ZA
ZA00770108A
patent/ZA77108B/en
unknown
1977-01-10
NL
NL7700158A
patent/NL7700158A/en
not_active
Application Discontinuation
1977-01-10
AU
AU21187/77A
patent/AU513804B2/en
not_active
Expired
1977-01-11
IE
IE45/77A
patent/IE45084B1/en
unknown
1977-01-11
IT
IT19160/77A
patent/IT1113502B/en
active
1977-01-11
JP
JP185777A
patent/JPS52154581A/en
active
Granted
1977-01-11
BE
BE173990A
patent/BE850275A/en
not_active
IP Right Cessation
1977-01-11
FR
FR7700619A
patent/FR2337755A1/en
active
Granted
1977-01-11
CA
CA269,477A
patent/CA1108037A/en
not_active
Expired
1977-01-11
IN
IN24/CAL/77A
patent/IN145036B/en
unknown
1977-01-11
NO
NO770095A
patent/NO770095L/en
unknown
1977-01-11
DK
DK9277A
patent/DK148713C/en
not_active
IP Right Cessation
1977-01-11
SE
SE7700228A
patent/SE7700228L/en
unknown
1977-01-12
LU
LU76551A
patent/LU76551A1/xx
unknown
1977-01-12
DE
DE2759342A
patent/DE2759342C3/en
not_active
Expired
1977-01-12
BR
BR7700203A
patent/BR7700203A/en
unknown
1977-01-12
DE
DE2701063A
patent/DE2701063B2/en
not_active
Withdrawn
1977-01-12
DE
DE19777700749U
patent/DE7700749U1/en
not_active
Expired
1987
1987-11-23
US
US07/124,351
patent/US4935347A/en
not_active
Expired – Lifetime
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Assignee
Title
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1982-04-14
1992-01-07
Radiometer Corporate Development Ltd.
Microorganism testing with a hydrolyzable fluorogenic substrate
GB2165216A
(en)
*
1982-10-08
1986-04-09
Analytichem Int Inc
Disposable sample cassette for high pressure chromatography
Also Published As
Publication number
Publication date
FI770035A
(en)
1977-07-13
IE45084B1
(en)
1982-06-16
IT1113502B
(en)
1986-01-20
US4935347A
(en)
1990-06-19
DE2701063B2
(en)
1979-10-11
JPS5642904B2
(en)
1981-10-07
FR2337755B1
(en)
1980-06-13
BE850275A
(en)
1977-07-11
DE7700749U1
(en)
1977-12-08
DE2701063A1
(en)
1977-07-21
NZ182997A
(en)
1979-03-28
DE2759342B1
(en)
1980-02-07
DK148713B
(en)
1985-09-09
FR2337755A1
(en)
1977-08-05
LU76551A1
(en)
1977-07-27
IE45084L
(en)
1977-07-12
SE7700228L
(en)
1977-07-13
DK9277A
(en)
1977-07-13
DE2759342C3
(en)
1985-12-05
NL7700158A
(en)
1977-07-14
BR7700203A
(en)
1977-09-20
JPS52154581A
(en)
1977-12-22
CA1108037A
(en)
1981-09-01
DK148713C
(en)
1986-04-01
AU2118777A
(en)
1978-07-20
AU513804B2
(en)
1981-01-08
NO770095L
(en)
1977-07-13
IN145036B
(en)
1978-08-12
ZA77108B
(en)
1978-08-30
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Legal Events
Date
Code
Title
Description
1980-11-26
PS
Patent sealed [section 19, patents act 1949]
1982-03-17
429A
Application made for amendment of specification (sect. 29/1949)
1982-06-09
429H
Application (made) for amendment of specification now open to opposition (sect. 29/1949)
1982-10-20
429D
Case decided by the comptroller ** specification amended (sect. 29/1949)
1982-11-24
SPA
Amended specification published
1985-07-24
732
Registration of transactions, instruments or events in the register (sect. 32/1977)
1988-12-07
732
Registration of transactions, instruments or events in the register (sect. 32/1977)
1996-08-28
PCNP
Patent ceased through non-payment of renewal fee
Effective date:
19960111
