GB1560475A - Pharmaceutical formulation - Google Patents

Pharmaceutical formulation Download PDF

Info

Publication number
GB1560475A
GB1560475A GB41744/75A GB4174475A GB1560475A GB 1560475 A GB1560475 A GB 1560475A GB 41744/75 A GB41744/75 A GB 41744/75A GB 4174475 A GB4174475 A GB 4174475A GB 1560475 A GB1560475 A GB 1560475A
Authority
GB
United Kingdom
Prior art keywords
tablet
volume
weight
determined
minutes
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.)
Expired
Application number
GB41744/75A
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.)
Lilly Industries Ltd
Original Assignee
Lilly Industries 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 Lilly Industries Ltd filed Critical Lilly Industries Ltd
Priority to GB41744/75A priority Critical patent/GB1560475A/en
Priority to AU18292/76A priority patent/AU514174B2/en
Priority to CA262,741A priority patent/CA1079637A/en
Priority to DD195197A priority patent/DD126926A5/xx
Priority to JP51121193A priority patent/JPS5247914A/en
Priority to AT749476A priority patent/AT348670B/en
Priority to US05/869,982 priority patent/US4143129A/en
Publication of GB1560475A publication Critical patent/GB1560475A/en
Expired legal-status Critical Current

Links

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
    • A61K31/54—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Cephalosporin Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

(54) PHARMACEUTICAL FORMULATION (71) We, LILLY INDUSTRIES LIMITED, a British company of Henrietta House, Henrietta Place, London, W.l., 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 pharmaceutical formulations, more particularly to tablets containing an orally active cephalosporin such as cephalexin or cephradine.
Both cephalexin (7 - (D - cr- - amino - phenylacetamido) - 3 - methyl - 3 - cephem 4 - carboxylic acid) and cephradine (7 - [D amino - (1,4 - cyclohexadienyl) - acetamidoi - 3 - methyl - 3 - cephem - 4 - carboxylic acid) are excellent broad spectrum antibiotics having low toxicity. However, for effective chemotherapy of bacterial infections in humans it has been found that quite high dosages are needed.
Consequentially, heretofore, administration of these cephalosporins has necessarily taken the form of either rather large tablets or numerous small tablets. Both of these forms of administration have undesirable facets so far as patient acceptability, particularly in children and the elderly, is concerned. Thus, there has long been a need for smaller tablets containing adequate amounts of active ingredient.
Accordingly, the present invention provides a tablet which comprises: (a) greater than 90% by weight of an orally active cephalosporin: (b) less than 10% by weight of excipients which comprise: (i) from 2 to 5% by weight of a binder which is polyvinyl pyrrolidone having a number average molecular weight of from 500,000 to 1,500,000; (ii) from 1.5 to 5% by weight of a disintegrant: and (iii) from 0.3 to 2%, by weight of a lubricant, and which has (c) a diametral crushing strength of from 5.0 to 15.0 Kg.; and (d) will disintegrate in distilled water within 15 minutes at 370C.
Preferably, the excipients will comprise from 2 to 4Oo by weight of binder, from 1.5 to 4 ^ by weight disintegrant and from 0.3 to 20n by weight of lubricant.
The tablet will contain approximately from 90 to 96%, preferably from 92 to 95", most preferably from 93 to 950,, by weight of the orally active cephalosporin. The preferred cephalosporin is cephalexin.
which is particularly useful in the practice of the invention when it is in the form of its monohydrate.
The use of polyvinyl pyrrolidone having a number average molecular weight of from 500,000 to 1,000,000 ideally approximately 700,000, as determined by viscosity measurements, as the binder is much preferred.
The disintegrant is preferably a sodium starch glycolate containing from 15 to 35, most preferably about 25, carboxymethyl groups per 100 glucose units, although other disintegrants such as zeolites of the type known by the trade name "Amberlite IRP 88", or sodium carboxymethylcellulose may be used.
Similarly, although the use of magnesium stearate as the lubricant is preferred, other lubricants such as stearic acid or calcium stearate can also be used.
Physicians commonly administer orally active cephalosporins in the form of tablets containing approximately 250, 500 or 1000 mg. of the active ingredient. The tablets according to the invention can be provided as follows:- (A) a tablet which contains approximately 250 mg. of an orally active cephalosporin, and which has a volume of from 0.20 to 0.23 ml., when determined by displacement of liquid paraffin; (B) a tablet which contains approximately 500 mg. of an orally active cephalosporin, and which has a volume of from 0.40-0.47 ml., when determined by displacement of liquid paraffin; and (C) a tablet which contains approximately 1000 mg. of an orally active cephalosporin, and which has a volume of from 0.80 to 0.95 ml., when determined by displacement of liquid paraffin.
The tablets of the invention may also comprise small amounts of other commonly used excipients, for instance they may be coloured by the use of suitable dyes or lakes.
In addition, if desired, the tablets of the invention may be coated using a polymer coating agent which is, for example, cellulose derivative such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose or methyl cellulose.
The tablets of the invention can be prepared by admixing the cephalosporin and excipients and then compressing the mixture. Preferably they are prepared by dissolving or dispersing the binder in water or a suitable organic solvent and using this solution or dispersion to mass and subsequently granulate the cephalosporin.
The granules are then passed through a sieve of suitable mesh size and dried. After resieving to break up any agglomerates the dried granules are combined with the lubricant and disintegrant and compressed into tablets using a conventional tabletting machine. If it is desired to produce coloured tablets, a dye may be added to the solution or dispersion of binder, or a lake to the dried powder blend prior to compression.
Coating of the tablets may be carried out subsequent to compression using appropriate coating equipment.
To further illustrate the invention and to show how the same may be carried into effect, reference will now be made to the following non-limitative examples.
EXAMPLE 1 This is an example of a conventional tablet containing cephalexin. - The ingredients were: mg.
Cephalexin monohydrate* 1000 'Primqiel't 44.4 Pregelatinised Starch 70 Flowable Starch 55.7 Magnesium Stearate 14.8 Stearic Acid 29.6 Starch dried q.s. 1480 *as determined by iodometric assay t trademark 'Primojel' is the trade name for a sodium starch glycolate containing approximately 25 carboxymethyl units per 100 glucose units.
The above ingredients were formulated into a tablet using conventional procedure.
Although the tablet prepared from the above ingredients was satisfactory, its volume was 1.15 ml. (as measured by displacement of liquid paraffin).
EXAMPLE 2 This is an example of a tablet of the invention.
mg.
Cephalexin monohydrate* 1000 'Kollidon 90't 24 'Primojel't 20 Magnesium Stearate 6 Total 1050 *as determined by iodometric assay t trademark The 'Kollidon 90', which is a polyvinyl pyrrolidone having a number average molecular weight of approximately 700,000.
as determined by viscosity measurements, was dissolved in water and then massed with the cephalexin monohydrate so as to form a granular material. After sieving, this material was dried and then resieved. The resieved mixture was then combined and intimately admixed with the 'Primojel' and magnesium stearate and compressed into a tablet.
The volume of the tablet, when measured by displacement of liquid paraffin, was 0.87 ml. It will be immediately appreciated that this is significantly less than the volume of the conventional tablet of Example 1.
The diametral crushing strength of this tablet, which is of course a measure of the hardness of the tablet, was measured using a Erweka tester type TBT (Erweka Apparatebau Gmbh., Frankfurt am Main, W. Germany) and was found to be 12 Kg., a quite satisfactory hardness. In addition, the disintegration time of this tablet was determined using the method described in the British Pharamcopoeia 1973 Appendix XIX A, pages A 131/2, i.e. in distilled water at 37"C.+2"C. and was found to be 4 minutes, a good disintegration time.
EXAMPLES 3 and 4 Using the procedure of Example 2, there were prepared tablets containing the ingredients listed below.
mg.
Cephalexin monohydrate* 500 'Primojel't 14 'Kollidon 90't 15 Magnesium Stearate 6 Total 535 Volume 0.43 ml.
Diametral Crushing Strength 11 Kg.
Disintegration Time 5 minutes.
mg.
Cephalexin monohydrate* 250 'Primojel't 8 'Kollidon 90't 8 Magnesium Stearate 4 270 *as determined by iodometric assay t trademark Volume 0.23 ml.
Diametral Crushing Strength 10 kg.
Disintegration Time 6 minutes.
Similarly, using the method described in Example 2, the following further tablets were prepared.
EXAMPLE 5 mg.
Cephalexin monohydrate* 1000 'Kollidon 90't 20 'Primojel't 15 Magnesium Stearate 3 1038 *as determined by iodometric assay t trademark Volume 0.856 ml.
Diametral Crushing Strength 10.5 Kg.
Disintegration Time 3 minutes.
EXAMPLE 6 mg.
Cephalexin monohydrate* 1000 'Kollidon 90't 20 'Amberlite IRP 88't 15 Magnesium Stearate 3 1038 *as determined by iodometric assay t trademark Volume 0.849 ml.
Diametral Crushing Strength 14.2 Kg.
Disintegration Time 5 minutes.
EXAMPLE 7 mg.
Cephalexin monohydrate* 1000 Kollidon 90't 25 'Primojel't 20 Stearic Acid 7 1052 *as determined by iodometric assay t trademark Volume 0.872 ml.
Diametral Crushing Strength 14 Kg.
Disintegration Time 13 minutes.
EXAMPLE 8 mg.
Cephalexin monohydrate* 1000 'Kollidon 90't 20 'Primojel'* 15 Stearic acid 7 F.D. & C. Yellow No. 6 Aluminium Lake ' 10 1052 *as determined by iodometric assay t trademark Volume 0.910 ml.
Diametral Crushing Strength 10 Kg.
Disintegration Time 2 minutes The F.D. & C. Yellow No. 6 Aluminium Lake used in Example 8 was combined with the 'Primojel' and the stearic acid and then mixed with cephalexin granules formed as in Example 2. The mixture thus formed was then compressed into a tablet.
WHAT WE CLAIM IS: 1. A tablet which comprises: (a) greater than 90% by weight of an orally active cephalosporin; (b) less than 10% by weight of excipients which comprise: (i) from 2 to 5% by weight of a binder which is polyvinyl pyrrolidone having a number average molecular weight of from 500,000 to 1,500,000: (ii) from 1.5 to 5% by weight of a disintegrant; and (iii) from 0.3 to 2% by weight of a lubricant, and which has (c) a diametral crushing strength of from 5.0 to 15.0 Kg.; and (d) will disintegrate in distilled water within 15 minutes at 370C.
2. A tablet as claimed in claim 1, wherein the orally active cephalosporin is 7 - (D - amino - phenylacetamido) - 3 - methyl - 3 cephem - 4 - carboxylic acid.
3. A tablet as claimed in claim 1 or 2, wherein the polyvinyl pyrrolidone has a number average molecular weight of from 500,000 to 1,000,000.
4. A tablet as claimed in any one of claims I to 3, wherein the disintegrant is a sodium starch glycolate containing from 15 to 35 carboxymethyl groups per 100 glucose units.
5. A tablet as claimed in any one of claims 1 to 4, wherein the lubricant is magnesium stearate.
6. A tablet as claimed in any one of claims I to 5 which contains approximately 1000 mg. of the orally active cephalosporin, and
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (10)

  1. **WARNING** start of CLMS field may overlap end of DESC **.
    mg.
    Cephalexin monohydrate* 250 'Primojel't 8 'Kollidon 90't 8 Magnesium Stearate 4
    270 *as determined by iodometric assay t trademark Volume 0.23 ml.
    Diametral Crushing Strength 10 kg.
    Disintegration Time 6 minutes.
    Similarly, using the method described in Example 2, the following further tablets were prepared.
    EXAMPLE 5 mg.
    Cephalexin monohydrate* 1000 'Kollidon 90't 20 'Primojel't 15 Magnesium Stearate 3
    1038 *as determined by iodometric assay t trademark Volume 0.856 ml.
    Diametral Crushing Strength 10.5 Kg.
    Disintegration Time 3 minutes.
    EXAMPLE 6 mg.
    Cephalexin monohydrate* 1000 'Kollidon 90't 20 'Amberlite IRP 88't 15 Magnesium Stearate 3
    1038 *as determined by iodometric assay t trademark Volume 0.849 ml.
    Diametral Crushing Strength 14.2 Kg.
    Disintegration Time 5 minutes.
    EXAMPLE 7 mg.
    Cephalexin monohydrate* 1000 Kollidon 90't 25 'Primojel't 20 Stearic Acid 7
    1052 *as determined by iodometric assay t trademark Volume 0.872 ml.
    Diametral Crushing Strength 14 Kg.
    Disintegration Time 13 minutes.
    EXAMPLE 8 mg.
    Cephalexin monohydrate* 1000 'Kollidon 90't 20 'Primojel'* 15 Stearic acid 7 F.D. & C. Yellow No. 6 Aluminium Lake ' 10
    1052 *as determined by iodometric assay t trademark Volume 0.910 ml.
    Diametral Crushing Strength 10 Kg.
    Disintegration Time 2 minutes The F.D. & C. Yellow No. 6 Aluminium Lake used in Example 8 was combined with the 'Primojel' and the stearic acid and then mixed with cephalexin granules formed as in Example 2. The mixture thus formed was then compressed into a tablet.
    WHAT WE CLAIM IS: 1. A tablet which comprises: (a) greater than 90% by weight of an orally active cephalosporin; (b) less than 10% by weight of excipients which comprise: (i) from 2 to 5% by weight of a binder which is polyvinyl pyrrolidone having a number average molecular weight of from 500,000 to 1,500,000: (ii) from 1.5 to 5% by weight of a disintegrant; and (iii) from 0.3 to 2% by weight of a lubricant, and which has (c) a diametral crushing strength of from 5.0 to 15.0 Kg.; and (d) will disintegrate in distilled water within 15 minutes at 370C.
  2. 2. A tablet as claimed in claim 1, wherein the orally active cephalosporin is 7 - (D - amino - phenylacetamido) - 3 - methyl - 3 cephem - 4 - carboxylic acid.
  3. 3. A tablet as claimed in claim 1 or 2, wherein the polyvinyl pyrrolidone has a number average molecular weight of from 500,000 to 1,000,000.
  4. 4. A tablet as claimed in any one of claims I to 3, wherein the disintegrant is a sodium starch glycolate containing from 15 to 35 carboxymethyl groups per 100 glucose units.
  5. 5. A tablet as claimed in any one of claims
    1 to 4, wherein the lubricant is magnesium stearate.
  6. 6. A tablet as claimed in any one of claims I to 5 which contains approximately 1000 mg. of the orally active cephalosporin, and
    which has a volume of from 0.80 to 0.95 ml., when determined by displacement of liquid paraffin.
  7. 7. A method of preparing a tablet as claimed in any one of claims 1 to 6 which comprises admixing the cephalosporin and excipients and then compressing the mixture to form the tablet.
  8. 8. A tablet as claimed in claim 1 substantially as hereinbefore described with reference to any one of Examples 2 to 8.
  9. 9. A method of preparing a tablet as claimed in claim 1 substantially as hereinbefore described with reference to any one of Examples 2 to 8.
  10. 10. A tablet whenever prepared by a method according to claim 7 or 9.
GB41744/75A 1975-10-11 1975-10-11 Pharmaceutical formulation Expired GB1560475A (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
GB41744/75A GB1560475A (en) 1975-10-11 1975-10-11 Pharmaceutical formulation
AU18292/76A AU514174B2 (en) 1975-10-11 1976-09-30 Improvements in or relating to tablets
CA262,741A CA1079637A (en) 1975-10-11 1976-10-05 Cephalosporine tablets
DD195197A DD126926A5 (en) 1975-10-11 1976-10-06
JP51121193A JPS5247914A (en) 1975-10-11 1976-10-08 Tablet and its prepation
AT749476A AT348670B (en) 1975-10-11 1976-10-08 PROCESS FOR THE MANUFACTURING OF CEPHALOSPORIN TABLETS
US05/869,982 US4143129A (en) 1975-10-11 1978-01-16 Cephalexin tablets

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB41744/75A GB1560475A (en) 1975-10-11 1975-10-11 Pharmaceutical formulation

Publications (1)

Publication Number Publication Date
GB1560475A true GB1560475A (en) 1980-02-06

Family

ID=10421183

Family Applications (1)

Application Number Title Priority Date Filing Date
GB41744/75A Expired GB1560475A (en) 1975-10-11 1975-10-11 Pharmaceutical formulation

Country Status (6)

Country Link
JP (1) JPS5247914A (en)
AT (1) AT348670B (en)
AU (1) AU514174B2 (en)
CA (1) CA1079637A (en)
DD (1) DD126926A5 (en)
GB (1) GB1560475A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5837292A (en) * 1996-07-03 1998-11-17 Yamanouchi Europe B.V. Granulate for the preparation of fast-disintegrating and fast-dissolving compositions containing a high amount of drug

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0052076B1 (en) * 1980-11-12 1985-05-29 Ciba-Geigy Ag Fast disaggregating pharmaceutical tablet
JPS59155310A (en) * 1983-02-21 1984-09-04 Daicel Chem Ind Ltd Production of solid medicinal preparation with improved disintegration
JPS59167522A (en) * 1983-03-14 1984-09-21 Daicel Chem Ind Ltd Production of solid drug
JPS59176217A (en) * 1983-03-28 1984-10-05 Daicel Chem Ind Ltd Powder composition for solid pharmaceutical preparation
JPS59193815A (en) * 1983-04-15 1984-11-02 Daicel Chem Ind Ltd Preparation of tablet
JPS62173183A (en) * 1986-01-25 1987-07-30 マツダ株式会社 Article mounting method to built-up carrying jig

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5837292A (en) * 1996-07-03 1998-11-17 Yamanouchi Europe B.V. Granulate for the preparation of fast-disintegrating and fast-dissolving compositions containing a high amount of drug
EP0910344B1 (en) * 1996-07-03 2003-04-16 Yamanouchi Europe B.V. Granulate for the preparation of fast-disintegrating and fast-dissolving compositions containing a high amount of drug

Also Published As

Publication number Publication date
AT348670B (en) 1979-02-26
JPS5247914A (en) 1977-04-16
JPS619283B2 (en) 1986-03-22
AU514174B2 (en) 1981-01-29
DD126926A5 (en) 1977-08-24
ATA749476A (en) 1978-07-15
AU1829276A (en) 1978-04-06
CA1079637A (en) 1980-06-17

Similar Documents

Publication Publication Date Title
US4143129A (en) Cephalexin tablets
US6440462B1 (en) Agglomerates of β-lactam antibiotics and processess for making agglomerates
US4842866A (en) Slow release solid preparation
KR960009182B1 (en) Pharmaceutical tablet and granulate and process for their preparation
AU767239B2 (en) Phosphate-binding polymer and tablets using the same
KR100202154B1 (en) Film coated tablet of paracetamol and domperidone
US3865935A (en) Tableting of erythromycin base
EP0159852A2 (en) Directly compressible pharmaceutical compositions
KR101197277B1 (en) Oral Solid Preparation For Treatment And Prevention Of Tuberculosis
US5322698A (en) Process for the preparation of a tablet or dragee composition containing a heat-, light- and moisture-sensitive active ingredient having monoclinic crystal structure
GB1560475A (en) Pharmaceutical formulation
US4601895A (en) Delayed-action acetylsalicylic acid formulations for oral administration
CA2502582A1 (en) Pharmaceutical formulation of olanzapine
JPH08310969A (en) Solid pharmaceutical composition and its preparation
US4086335A (en) Pharmaceutical tablets containing chitin as a disintegrant
FI89455B (en) Foerfarande Foer framstaellning av en pharmaceutical pharmaceutical composition
AU2002224011A1 (en) A pharmaceutical composition for controlled release of a beta-lactam antibiotic
US6485744B1 (en) Stabilized cefuroxime axetil
GB2061111A (en) Long acting pharmaceutical composition
EP0973508A1 (en) Pharmaceutical tablet of amiodarone salt
CA2343949A1 (en) Benazepril hydrochloride tablet formulations
US3740432A (en) Vitamin complexes of niacinamide,riboflavin and sodium ascorbate
WO2001049246A2 (en) Sustained release tablet formulations comprising clarithromycin
CN104127392A (en) Cefalexin capsule and preparation process thereof
US3681493A (en) Antibacterial compositions

Legal Events

Date Code Title Description
PS Patent sealed
704A Declaration that licence is not available as of right for an excepted use (par. 4a/1977)
PE20 Patent expired after termination of 20 years

Effective date: 19961010