IE46580B1 - Pellets suitable for use in the testing of microorganisms - Google Patents

Pellets suitable for use in the testing of microorganisms

Info

Publication number
IE46580B1
IE46580B1 IE529/78A IE52978A IE46580B1 IE 46580 B1 IE46580 B1 IE 46580B1 IE 529/78 A IE529/78 A IE 529/78A IE 52978 A IE52978 A IE 52978A IE 46580 B1 IE46580 B1 IE 46580B1
Authority
IE
Ireland
Prior art keywords
pellet
pellet according
reagent
test reagent
carrier
Prior art date
Application number
IE529/78A
Other versions
IE780529L (en
Original Assignee
Beecham Group Ltd
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.)
Filing date
Publication date
Application filed by Beecham Group Ltd filed Critical Beecham Group Ltd
Publication of IE780529L publication Critical patent/IE780529L/en
Publication of IE46580B1 publication Critical patent/IE46580B1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Toxicology (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Tablet for the investigation of microorganisms, characterised in that it contains a microporous solid, non-friable solution of a test reagent, such as an antibacterial agent, e.g. antibiotic, and an organic excipient.

Description

This invention relates to test materials. More specifically this invention relates to pellets containing test reagents.
It is well known that the sensitivity of micro5 organisms such as bacteria to antibiotics can be determined conveniently on a micro-scale. In one conventional method, a serial dilution of the antibiotic is prepared and incorporated into suitable media, such as broth or agar, and each dilution strength inoculated in the usual manner 1° with the bacteria. By observing the minimum antibiotic concentration at which bacterial growth is absent, the M.I.C. of the antibiotic can be obtained. In a second, conventional method, paper discs impregnated with the antibiotic are placed on agar plates inoculated with the bacteria, and the growth observed. A zone around each disc is obtained (provided the antibiotic concentration in the disc is sufficient) in which the difused antibiotic concentration has been high enough to prevent growth. From the dimensions of the zones and the antibiotic concentration in the discs, the M.I.C. of the antibiotic against that bacteria can be calculated.
Also, it is known to test an unknown micro-organism for its identity using materials giving a positive reaction in the presence of a given micro-organism.
We have now discovered that pellets may be prepared containing test reagents. These pellets are convenient easily handled sources of accurate micro-dosage quantities of the test reagents, and may be used, for example, as such in conventional microorganism testing of the kind hereinbefore described.
Accordingly, the present invention provides a pellet suitable for use in the testing of microorganisms, which pellet comprises a non-friable microporous solid solution of a test reagent and an organic carrier.
Now that the pellets of the invention and their desirable properties have been discovered, it is a routine matter for a skilled man to determine suitable organic carriers for use therein. For example, the freeze drying process hereinafter described may simply be repeated with a chosen reagent and carrier and the resultant pellet examined for non-friability and microporosity.
More specifically we have found that any organic carrier is suitable that can be freeze dried to give a non-friable microporous matrix. This matrix is preferably hydrophilic and non-hygroscopic, and is of course bacteriologically inert and compatible with the reagent.
The pellet formed therefrom will suitably be sufficiently rigid to prevent ready deformation thereof by handling.
Conveniently the carrier will be water soluble, thereby enabling ready release of reagent from the pellet on contact with aqueous media.
Examples of suitable organic carriers include certain organic synthetic polymers such as polyvinyl pyrrolidone and polyvinyl pyrrolidone/polyvinyl acetate 6 5 8 0 copolymers; certain organic semi-synthetic polymers such as methyl and hydroxypropylmethylcellulose, and sodium carhoxymethylcellulose, and other cellulose polymers; certain saccharides such as sucrose and lactose; and mannitol.
Particularly suitable organic polymers include polyvinyl pyrrolidone (such as the material available from BASF under the trade name Kollidon (25) ), and polyvinyl pyrrolidone/polyvinyl acetate copolymers (such as the material available from BASF under the trade name KQllidon VA64).
The test reagent may be a material capable of giving a positive Identification of a particular microorganism, or class of microorganism, such as the cytochrome oxidase reagent.
The test reagent may also be an anti-bacterial agent. Examples of suitable anti-bacterial agents include β-lactam antibiotics such as benzylpenicillin, phenoxy-methylpenicillin, carbenicillin, methicillin, propicillin, ampicillin, amoxycillin, epicillin, ticarcillin, cyclacillin, cephatriazine cephaloridine, cephalothin, cefazolin, cephalexin, cefoxitin, cephacetrile, cephamandole, cephapirin, cephradine, cephaloglycine, and other well known penicillins and cephalosporins or pro-drugs therefor such as hetacillin, metampicillin, the acetoxymethyl, pivaloyloxymethyl or phthalidyl esters of benzylpenicillin, ampicillin, amoxycillin or cephaloglycine, or the phenyl, tolyl or indanyl α-esters of carbenicillin - 4 46580 or ticarcillin or the like; and salts thereof when appropriate; aminoglycoside antibiotics such as gentamycih; macrolide antibiotics such as erythromycin ; pseudomonic acid and its salts and esters; the antibiotic known as MM455O and salts thereof; the antibiotic known as MM139O2 and salts thereof; the antibiotic known as MM1788O and salts thereof; thienomycin; and clavulanic acid, its salts, esters and ethers.
Pseudomonic acid has the structure (X): (I) It is fully described in British Patent Specification No. 1395907, MM455O has the structure (II); (II) (III) 6 5 8 0 MM1788O has the structure (IV): The preparation and properties of MM455O, MM139O2 and MM1788O and their salts are fully described in Patent Specification Nos. 40864 , 40824 .and 42489.
Clavulanic acid has the structure (V): The preparation and properties of clavulanic acid, its salts and esters are fully described in Belgian Patent No. 827926 and Offenlegungsschrift No. 2517316. The preparation and properties of the ethers (for example the methyl and ethyl ethers) of clavulanic acid are fully described in Offenlegungsschrift. No. 2646004.
The disclosure of these Patents and Offenlegungsschrifts is hereby incorporated by reference.
MM4550, MM139O2, MM1788O and their salts, and clavulanic acid, its salts, esters and ethers are synergists for β-lactam antibiotics. Thus the test reagent in the pellet will often be a β-lactam antibiotic and one of the - 6 46580 aforesaid synergists. Conveniently the weight ratio range of β-lactam antibiotic to synergist will be about 10:1 to 1:10.
Particularly useful synergists for this use are 5 salts of clavulanic acid, such as the lithium, sodium, potassium and calcium and like salts conventionally formed with penicillins and cephalosporins, particularly the sodium and potassium salts; and ethers of clavulanic acid such as the methyl and ethyl ethers.
Particularly suitable β-lactam antibiotics for use with clavulanic acid derivatives include a penicillin or a cephalosporin having a side chain (joined at the 6- or 7position respectively) of formula (VI): D R - CK - CO - (VI) nh2 wherein R is phenyl, p-hydroxyphenyl or cyclohexadienyl, or a salt thereof. Suitable penicillins of this type include ampicillin and amoxycillin, and salts thereof such as the sodium and potassium salts. Suitable clavulanic acid derivatives include those clavulanic acid salts listed hereinbefore.
In these formulations the ratio of antibiotic to clavulanic acid or derivative thereof will normally be in the range 10:1 to 1:10 (w/w), for example 5:1 to 1:1.
The proportions of the reagent to the carrier in 25 the pellet may be varied as desired, provided of course 46S80 there remains sufficient carrier to form the matrix. For example suitable pellets may contain 0.1 to 25 pec cent by weight reagent, mare suitably 0.1 to 10% reagent.
The shape of the pellet is unimportant provided it is destined to be dissolved in a solvent (for example in aqueous media to provide a solution of standard reagent concentration, as in M.I.C. testing by serial dilution).
In such cases the pellets can be spheroid, hemi-spheroid, frustro-conical, discoid, or any other convenient shape. However when the pellets are to be used in place of paper sensitivity discs in agar plate sensitivity testing, then it is essential that they have at least one flat circular surface for contacting the agar to allow controlled diffusion of reagent therefrom. With this in mind, pellets for this use are suitably of the same general size and shape as the known paper sensitivity discs.
By way of illustration, the pellets will suitably have a largest diameter of about 2 to 10 mm, for example, about 6 mm. Again by way of illustration only, the pellets may suitably weigh 0.001 to 0.1 g, more suitably 0.005 to 0.05 g.
The invention also provides a process for the preparation of the pellets as hereinbefore defined, which process comprises freeze drying a solution of the reagent and the carrier. - 8 46580 Suitably portions of the solution are filled into moulds or dropped onto a suitable flat surface, or the like, and the freeze drying step then carried out.
Depending on the solubilities of the reagent and 5 carrier, the necessary solution may be prepared in aqueous, organic or mixed solvents. The reagent and the carrier will be dissolved in the solvent in the relative proportions desired in the pellets to be prepared from that solution. Examples of suitable solvents include inert volatile solvents 1.0 such as those solvents suitable for use in freeze drying, for example water, t-butanol, acetonitrile, dimethyl carbonate dimethyl sulphoxide and the like. Where possible water will be used as the solvent.
Suitably the solution to be freeze dried will contain about 3 to 25% carrier.
It has been found that applying the freeze drying technique to conventional paper discs wetted with reagent solution has a number of disadvantages, for example poor or incomplete contact with the heat-transfer medium and formidabl handling problems both before and after the drying stage.
These disadvantages are overcome when the freeze drying technique is used in the process of this invention.
The pellets of this invention should be stored in the presence of a desiccant.
The pellets of the invention may be used to provide a known micro-dosage quantity of a reagent for use in the © S 8 Ο ς testing of micro-organisms. For example (i) When the reagent is an indicator for a particular micro-organism, then the pellets can be used to establish the identity of an unknown microorganism, thereby enabling an effective drug therapy to be designed there against. (ii) When the reagent is an anti-bacterial agent, the sensitivity of a particular micro-organism to that anti-bacterial agent can be established by conventional M.I.C. or agar plate zone inhibition methods.
The pellets may also be used to provide accurate micro-dosage quantities of the test reagent for purposes other than micro-organism sensitivity testing, for example for chemical tests on the reagent itself.
The pellets have the additional advantages that: (i) They improve the solubility of sparingly soluble or insoluble reagents. (ii) When prepared by freeze drying, they have good stability with reagents unstable in solution or during drying procedures at normal temperatures. (iii) The use of water soluble carriers therein results in the reagent being completely available to aqueous media. (iv) (ν) (vi) The They have good reproducibility.
They can be made sterile if so desired.
They are easily handled, for example with tweezers. following Examples illustrate the invention.
Example 1 Pellets consisting of sodium amoxycillin and lithium clavulanate in solid solution with Kollidon (25) 110 mg of sodium amoxycillin was dissolved in 25 ml water. 64 mg of lithium clavulanate was dissolved in a separate 20 ml of water. 3 ml of the amoxycillin solution and 2 ml of the clavulanic acid solution were added to a solution of 2 g of Kollidon (25) in 10 ml water. The solution was then brought to 20 ml with water. 50 mg drops of the solution were placed on a stainless steel tray at room temperature and then frozen at -40°C for one hour. A vacuum was then applied and the samples freeze-dried over 24 hours, with a final drying temperature of 40°C, to give pellets.
These pellets are hard, non-friable microporous discs.
Example 2 Pellets consisting of disodium ticarcillin and lithium clavulanate 100 mg of disodium ticarcillin was dissolved in 5 50 ml water. 33 mg of lithium clavulanate was dissolved in a separate 100 ml of water. 5 ml of the ticarcillin solution and 5 ml of the clavulanic acid solution were added to a solution of 3 g Kollidon VA64 in 10 ml of water. mg drops of the combined solution were placed on a stainless steel tray at room temperature and then frozen at -40°C for 1 hour. A vacuum was then applied and the samples freeze dried over 24 hours, with a final drying temperature of 40°C, to give pellets.
These pellets were hard, non-friable microporous discs The pellets shown in the Table were prepared in similar manner as indicated. They were of a generally discoidal shape, and were all non-friable and microporous. 4©S©0 Final carrier cone, in freeze dried solution in H = = = = c'P in M i/.O = d0 in rd Drop weight Cn £ ID = = = cn £ O co I—1 = = = t Method of Prep. ! 33 cd cd £ £ CM CM +5 3 3 r-l r-l £ £ in in + = = = = = = = Carrier, and cone, of carrier solution (B) •Π* > G o > '0 \ •H 5 rd rd 0 o W «Ό = = = = > υ 5 2 Ο ϋ!> W 00 Φ > ω X 2s U C'.a to o W oo > . o S 3 U W CO = Φ > in \ 0 5 Id ϋ o’." to O w co Cone, of original reagent solution (A) TJ •d o β o φ CM ω a Id 4-1 rd £ CP £ co O G CM id = c o •rd CM K CP £ *—ι £ co n in o G CM •rl ffi CnH £ £ CM O in cm o G CM •rl ffi tT* r-d β e oo O cm m G O •d CM a tn £ ·—I £ στ • O CM O CO ι—1 = 85.4 mg in IOO ml water o CM C ffi •d r-d £o IO O Π rd = Reagent + ug reagent/disc G Ή 0 >1 £ Cn (fl □. 4J C O Φ in CJ CM fi •rd □ ti 0 Id Cn χ: .-λ X» >o ut m W CM 0 •d G £ o cn TJ to to tj φ Ή o ω u tn CU < CM Cytochrome Oxidase Reagent 100 ug > to rd 0 £ to ri tn x: to4J •d o J CM & ι—1 0 •h cn x: to 4J •d o Ul CM > ffl rd ϋ •d Cn x: xi P •d o »4 cl 3.S rd rd Cm rd P‘d 3 5 cn •d ft to rto 0 0 rd O M 0 tn C •d rd rd d o cn •d .'1 Q< £ O rf, CM G •d rd rd •d 0 0’ •d ;□ IX £ O Example No. n m ID c* CO Ch o r-i rd |—i CM rd Notes S.C.M.C. is sodium carboxymethylcellulose.
Kollidon VA64 is a water soluble copolymer of 60. vinyl pyrrolidone, 40% vinyl acetate.
The pellets of Examples 3 to 12 were also made in blister pack tops and in a metal former, yielding pellets of a generally frustro-conical and discoidal shape respectively.
The S.C.M.C. discs were deformable but not friable.

Claims (10)

CLAIMS:1. A pellet suitable for use in the testing of microorganisms, which pellet comprises a non-friable microporous solid solution of a test reagent and
1. ° carrier is water soluble. 2. ° therefor.
2. A pellet according to claim 1, wherein the carrier is a material that can be freeze dried to give a non-friable microporous matrix.
3. A pellet according to claim 1 or 2, wherein the
4. A pellet according to claim 3, wherein the carrier is polyvinyl pyrrolidone or a polyvinyl pyrrolidone/ polyvinyl acetate copolymer.
5. A pellet according to any one of the claims 1 to 4, 15 wherein the test reagent is an anti-bacterial agent. 5 an organic carrier.
6. A pellet according to claim 5, wherein the test reagent is a β-lactam antibiotic.
7. A pellet according to claim 5, wherein the test reagent is a β-lactam antibiotic and a synergist
8. A pellet according to claim 7, wherein the test reagent is a penicillin or a cephalosporin having a side chain (joined at the 6- or 7- position respectively) of formula (VI): D R - CH - CO I NH 2 (VI) wherein R is phenyl, p-hydroxyphenyl or cyclohexadienyi, or a salt thereof; and clavulanic acid, a salt, ester or ether thereof.
9. A pellet according to claim 8, wherein the weight ratio of penicillin or cephalosporin to clavulanic acid or derivative thereof is 5:1 to 1:1. 10. A pellet according to any one of the claims 1 to 9, wherein the reagent represents 0.1 to 25 per cent by weight of the pellet. 11. A pellet according to any one of the claims 1 to 10, wherein the pellet weighs 0.001 to 0.1 g. 12. A pellet according to any one of the claims 1 to 11, which has a largest diameter of about 2 to 10 mm. 13. A pellet according to any one of the claims 1 to 12, having a discoidal shape. 14. A pellet according to any one of the claims 1 to 13, containing a specific micro-dosage of the test reagent. 15. A process for the preparation of the pellet according to ciaim 1, which process comprises freeze drying a solution of the reagent and the carrier. 16. A process according to claim 15, wherein the solution is filled into moulds, or dropped onto a flat surface, and then freeze dried. 17. A process according to claim 15 or 16, wherein the solvent used to form the solution is water. 18. A process according to claim 15, 16 or 17, wherein the solution freeze dried has a carrier concentration of 3 to 25% (w/v). ^©500 19. 19. 20. 21. 20. 21. 10 22.
10. 22. A pellet according to claim 1, substantially as hereinbefore described with reference to any one of the Examples 1 to 12. A procesb for preparing a pellet according to claim 15, substantially as hereinbefore described with reference to any one of the Examples 1 to 12. A pellet according to claim 1, whenever prepared by a process according to any one of the claims 15 to 18, and 20. A method of testing the sensitivity of a microorganism ff to a test reagent, which method comprises contacting the microorganism with the test reagent when derived from a pellet according to any one of the claims 1 to 14, 19 and 21.
IE529/78A 1977-03-16 1978-03-15 Pellets suitable for use in the testing of microorganisms IE46580B1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB11060/77A GB1594001A (en) 1977-03-16 1977-03-16 Pellets suitable for use in the testing of microorganisms

Publications (2)

Publication Number Publication Date
IE780529L IE780529L (en) 1978-09-16
IE46580B1 true IE46580B1 (en) 1983-07-27

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ID=9979270

Family Applications (1)

Application Number Title Priority Date Filing Date
IE529/78A IE46580B1 (en) 1977-03-16 1978-03-15 Pellets suitable for use in the testing of microorganisms

Country Status (14)

Country Link
JP (1) JPS5435279A (en)
AU (1) AU523959B2 (en)
BE (1) BE864841A (en)
CA (1) CA1126138A (en)
CH (1) CH636643A5 (en)
DE (1) DE2810056A1 (en)
DK (1) DK152296C (en)
FR (1) FR2384022A1 (en)
GB (1) GB1594001A (en)
IE (1) IE46580B1 (en)
NL (1) NL7802799A (en)
NZ (1) NZ186646A (en)
SE (1) SE7802928L (en)
ZA (1) ZA781368B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2964817D1 (en) * 1978-09-06 1983-03-24 Beecham Group Plc Pharmaceutical compositions containing two beta-lactam derivatives
DE2965732D1 (en) * 1978-12-08 1983-07-28 Beecham Group Plc Pharmaceutical composition comprising a water soluble salt of amoxycillin and polyvinylpyrrolidone, and a vial containing a unit dose of said composition
CA2088047C (en) * 1990-12-21 1995-08-29 Matsuhisa Inoue Cephalosporinase testing agent
ATE153702T1 (en) * 1991-05-06 1997-06-15 Dade Microscan Inc RAPID SELECTION TEST FOR INDUCABLE BETA-LACTAMASE
US5350679A (en) * 1993-06-14 1994-09-27 Dow Corning Corporation Repeat insult microbial test method

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3138544A (en) * 1961-05-03 1964-06-23 British Drug Houses Canada Ltd Microbial sensitivity testing device
GB1057000A (en) * 1964-12-10 1967-02-01 Deputy Minister Of The Ministe Method of making tablets for testing the sensitivity of bacteria to an antibiotic
GB1275706A (en) * 1970-07-07 1972-05-24 Inst Pentru Controlul De Stat Microtablets for determining the sensitivity of microorganisms to antibiotics and chemotherapeutics
US3928566A (en) * 1970-08-14 1975-12-23 Du Pont Lyophilized biological products
US3932943A (en) * 1970-08-14 1976-01-20 E. I. Du Pont De Nemours And Company Method of preparation of lyophilized biological products
NZ177159A (en) * 1974-04-20 1978-03-06 Beecham Group Ltd Clavulanic acid, salts, esters and preparation thereof from streptomyces clavuligerus: pharmaceutical compositions
AU1087176A (en) * 1975-03-03 1977-08-11 Miles Lab Water soluble microbial composition
US4153512A (en) * 1976-04-07 1979-05-08 Fisher Scientific Company Storage stable antibiotic susceptibility test kit and method of testing

Also Published As

Publication number Publication date
GB1594001A (en) 1981-07-30
NL7802799A (en) 1978-09-19
NZ186646A (en) 1981-03-16
DK117678A (en) 1978-09-17
CH636643A5 (en) 1983-06-15
ZA781368B (en) 1979-02-28
DK152296C (en) 1988-07-11
IE780529L (en) 1978-09-16
SE7802928L (en) 1978-09-17
DE2810056A1 (en) 1978-09-28
JPS5435279A (en) 1979-03-15
AU523959B2 (en) 1982-08-26
CA1126138A (en) 1982-06-22
AU3421578A (en) 1979-09-20
BE864841A (en) 1978-09-13
DK152296B (en) 1988-02-15
FR2384022A1 (en) 1978-10-13
DE2810056C2 (en) 1987-09-03
FR2384022B1 (en) 1980-08-29

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