AU5761696A - Composition of tyrosine and polymerised allergen - Google Patents

Composition of tyrosine and polymerised allergen

Info

Publication number
AU5761696A
AU5761696A AU57616/96A AU5761696A AU5761696A AU 5761696 A AU5761696 A AU 5761696A AU 57616/96 A AU57616/96 A AU 57616/96A AU 5761696 A AU5761696 A AU 5761696A AU 5761696 A AU5761696 A AU 5761696A
Authority
AU
Australia
Prior art keywords
allergen
tyrosine
solution
composition according
polymerised
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.)
Granted
Application number
AU57616/96A
Other versions
AU705873B2 (en
Inventor
Iain Taylor
Alan Worland Wheeler
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.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham 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 SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of AU5761696A publication Critical patent/AU5761696A/en
Application granted granted Critical
Publication of AU705873B2 publication Critical patent/AU705873B2/en
Anticipated expiration legal-status Critical
Expired legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/35Allergens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/35Allergens
    • A61K39/36Allergens from pollen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pulmonology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

COMPOSITION OF TYROSINE AND POLYMERISED ALLERGEN
This invention relates to novel compositions for use in desensitisation therapy of allergy sufferers.
GB-A-1 492 973 describes a process for preparing coprecipitates of tyrosine having a modified allergen dispersed therein. The allergen has been modified by treatment with an agent, such as glutaraldehyde, which causes intra-molecular cross- linking and reduces the allergenicity of the product relative to the unmodified allergen.
EP-A-0 367 306 and Nakada et al (Allergy, 54 [1985] 437 et seq.) describe processes for preparing polymerised allergens by prolonged treatment with a cross- linking agent to cause intermolecular cross-linking, followed by filtration or dialysis to remove unpolymerised product. The polymerised allergens are described as having reduced allergenicity.
According to the present invention there is provided a pharmaceutical composition comprising tyrosine and a polymerised allergen. Typically, the allergen is coated with and /or adsorbed onto tyrosine, for example by co-precipitation.
The allergen may be derived from any allergy causing substance, such as a pollen (e.g. ragweed or birch pollen), food, insect venom, mould, animal fur, or house dust mite (D. farinae or D. pteronyssinus). In a particular aspect the allergen is derived from D. pteronyssinus. As used herein, "allergen" includes a mixture of allergens which may be from a single source or more than one source.
A further aspect of the invention provides a process for the preparation of a pharmaceutical composition in accordance with the invention, which process comprises (a) polymerising an allergen, (b) mixing an aqueous solution of the allergen with a solution of tyrosine in a strong aqueous acid, (c) neutralising the mixture of solutions, thereby co-precipitating tyrosine and polymerised allergen, and (d) optionally, mixing the product with a physiologically acceptable carrier. Suitable physiologically acceptable carriers include phenol-saline and sterile water.
The allergen is polymerised by treatment with a dialdehyde such as glutaraldehyde, in aqueous solution at a pH of 3 to 10, typically 7*1 and a temperature of between 0 and 100 °C, typically between 4 and 37 °C. for up to 10 hours, for example about two hours at room temperature. The ratio of allergen to glutaraldehyde is typically in the range 1:25 to 1:2, for example about 1 :4 w/w, although higher allergen ratios may be used in conjunction with a longer reaction time (see for instance EP-A-0 367 306, which uses ratios of about 3:1 and a reaction time of about seven hours). Low molecular weight product is then removed by gel filtration or dialysis, for example, tangential flow dialysis, and the product freeze dried or used directly in the next stage. The molecular weight cut off is typically at least 100 kDaltons, for example at least 250 kDaltons, more preferably 300 kDaltons. A solution of the polymerised allergen at pH 7±1, obtained either as the reaction mixture from the polymerisation process or from the solvation of a solid, is then mixed with a solution of tyrosine in a strong aqueous acid. The strong acid is usually an inorganic acid, preferably hydrochloric acid. The solution of polymerised allergen used in this step typically contains between 0.1 μg ml and 100 μg/ml allergen protein. The ratio of allergen: tyrosine in the mixture is typically in the range 1:4 x 105 to 1:4 x 102 w/w.
The resulting mixture of solutions of allergen and tyrosine is neutralised. By neutralisation is meant an adjustment of pH to a value within the range 4.0 to 7.5. It is important that, at no time, or at least at no prolonged time, during the neutralisation does the pH of the solution rise appreciably above 7.5. This condition can be met by vigorous stirring of the solution and by the use only of the required amount of base, if desired. Various buffering agents can usefully be added to the solutions of allergen to assist in pH control during the mixing and neutralising stages.
A particularly useful method of carrying out the neutralisation is for separate streams of the solution of tyrosine in acid and the neutralising base to be run into the solution of allergen. The rates of flow of the added solutions are controlled by pH- state, that is by equipment which regulates the flow of one or both of the solutions so that the pH of the reaction mixture remains substantially constant at a predetermined level. We have found that optimum results are usually obtained by pH control within the range 6.5 to 7.5 though the precise pH may vary according to the nature of the allergen.
The result of the neutralisation is the immediate precipitation of the tyrosine, within and or upon which the solution of allergen is occluded and/or adsorbed. After the precipitation the mixture is either washed immediately or allowed to stand for a period of from a few hours to a day or two prior to washing. Desirably the precipitate is obtained as fine as possible and this is achieved by rapid neutralisation of the solution coupled with vigorous agitation while this is being carried out.
The resulting precipitate may be removed from the solution by centrifugation or filtration and washed, e.g. with phenol-saline, before being resuspended in a physiologically-acceptable carrier such as phenol-saline, or sterile water, to produce an injectable composition suitable for use in desensitisation therapy.
The following Example illustrates the present invention: Example
A neutral solution of approximately 2.5 mg/ml D. pteronyssinus extract protein which had been partially purified by dialysis or fractionation was polymerised by the addition of an equal volume of 1% w/v glutaraldehyde and the mixture stirred for approximately 2 hours at room temperature. The reaction was quenched by the addition of an equal volume of 2% w/v glycine and the mixture stirred for a further one hour at room temperature. Low molecular weight material was removed by diafiltration across a membrane with a molecular weight exclusion of 300 kDaltons. The mixture was then sterile filtered and freeze dried.
A solution of the polymerised allergen was prepared either directly from the sterile filtered solution or by reconstitution of the freeze dried solid. This solution contained lOμg/ml in phosphate buffer pH 7±1. The allergen solution was co- precipitated with tyrosine by the simultaneous addition of one volume of L-tyrosine in HCl (prepared by dissolving 24g L-tyrosine to 100ml with 3.4M HCl) and one volume of 3.2M NaOH, to four volumes of allergen solution, with vigorous agitation. The suspension so formed was centrifuged, washed repeatedly with buffered saline to remove contaminants and resuspended to the original volume in buffered saline pH6 ±1.

Claims (7)

Claims
1. A pharmaceutical composition comprising tyrosine and a polymerised allergen.
2. A composition according to claim 1 wherein the allergen is coated with and/or adsorbed onto tyrosine.
3. A composition according to claim 1 or 2 wherein the allergen is derived from D. pteronyssinus.
4. A process for the preparation of a pharmaceutical composition according to any one of the preceding claims, which process comprises (a) polymerising an allergen, (b) mixing an aqueous solution of the allergen with a solution of tyrosine in a strong aqueous acid, (c) neutralising the mixture of solutions, thereby co-precipitating tyrosine and polymerised allergen, and (d) optionally, mixing the product with a physiologically acceptable carrier.
5. A composition according to any one of claims 1 to 3, for use in therapy.
6. A composition according to any one of claims 1 to 3, for use in desensitization therapy of allergy sufferers.
7. Use of a composition according to any one of claims 1 to 3 in the manufacture of a medicament for use in desensitization therapy of allergy sufferers.
AU57616/96A 1995-04-29 1996-04-25 Composition of tyrosine and polymerised allergen Expired AU705873B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9508785 1995-04-29
GBGB9508785.4A GB9508785D0 (en) 1995-04-29 1995-04-29 Novel compositions
PCT/EP1996/001733 WO1996034626A1 (en) 1995-04-29 1996-04-25 Composition of tyrosine and polymerised allergen

Publications (2)

Publication Number Publication Date
AU5761696A true AU5761696A (en) 1996-11-21
AU705873B2 AU705873B2 (en) 1999-06-03

Family

ID=10773769

Family Applications (1)

Application Number Title Priority Date Filing Date
AU57616/96A Expired AU705873B2 (en) 1995-04-29 1996-04-25 Composition of tyrosine and polymerised allergen

Country Status (20)

Country Link
EP (1) EP0825874A1 (en)
JP (1) JPH11504338A (en)
KR (1) KR19990008120A (en)
CN (1) CN1132629C (en)
AU (1) AU705873B2 (en)
BG (1) BG63990B1 (en)
BR (1) BR9608123A (en)
CA (1) CA2217388A1 (en)
CZ (1) CZ288401B6 (en)
EA (1) EA199700271A1 (en)
GB (1) GB9508785D0 (en)
HK (1) HK1010834A1 (en)
HU (1) HUP9802237A3 (en)
NO (1) NO974893L (en)
NZ (1) NZ308080A (en)
PL (1) PL183484B1 (en)
SK (1) SK281877B6 (en)
TR (1) TR199701265T1 (en)
WO (1) WO1996034626A1 (en)
ZA (1) ZA963340B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9706957D0 (en) * 1997-04-05 1997-05-21 Smithkline Beecham Plc Formulation
GB9820525D0 (en) 1998-09-21 1998-11-11 Allergy Therapeutics Ltd Formulation
GB0000891D0 (en) 2000-01-14 2000-03-08 Allergy Therapeutics Ltd Formulation
GB201106802D0 (en) 2011-04-21 2011-06-01 Allergy Therapeutics Ltd Process for preparing vaccine composition

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1377074A (en) * 1971-07-13 1974-12-11 Beecham Group Ltd Process for preparing injectable compositions
US4070455A (en) * 1974-02-16 1978-01-24 Beecham Group Limited Process for preparing injectable desensitizing compositions and products thereof in microparticle form
EP0058021A3 (en) * 1981-02-06 1982-10-27 Beecham Group Plc Pharmaceutical compositions
ES2013359A6 (en) * 1988-11-04 1990-05-01 Corporacion Biolog Farmaceutic Procedure for polymerized allergenis production.

Also Published As

Publication number Publication date
EA199700271A1 (en) 1998-04-30
NZ308080A (en) 1999-05-28
BG63990B1 (en) 2003-09-30
EP0825874A1 (en) 1998-03-04
ZA963340B (en) 1997-03-27
KR19990008120A (en) 1999-01-25
PL323104A1 (en) 1998-03-16
CN1132629C (en) 2003-12-31
HK1010834A1 (en) 1999-07-02
NO974893D0 (en) 1997-10-23
TR199701265T1 (en) 1998-02-21
HUP9802237A2 (en) 1999-02-01
CN1183046A (en) 1998-05-27
AU705873B2 (en) 1999-06-03
JPH11504338A (en) 1999-04-20
WO1996034626A1 (en) 1996-11-07
BG102004A (en) 1998-11-30
SK281877B6 (en) 2001-08-06
BR9608123A (en) 1999-02-09
HUP9802237A3 (en) 2000-06-28
CA2217388A1 (en) 1996-11-07
CZ342997A3 (en) 1998-03-18
GB9508785D0 (en) 1995-06-21
CZ288401B6 (en) 2001-06-13
NO974893L (en) 1997-10-23
PL183484B1 (en) 2002-06-28
SK146197A3 (en) 1998-05-06

Similar Documents

Publication Publication Date Title
EP0018561B1 (en) Process for the stabilization of blood clotting factors
US5904936A (en) Particles based on polyamino acid(s) and capable of being used as delivery vehicles for active principle(s) and method for preparing them
DE602005004014T2 (en) PROCESS FOR SOLUBILIZING PEPTIDE MIXTURES
CA2126685A1 (en) Process for the production of microcapsules
US6616948B2 (en) Starch
EP0941068B1 (en) Controlled release microspheres
US4070455A (en) Process for preparing injectable desensitizing compositions and products thereof in microparticle form
WO2009155626A2 (en) Functionally intact fibrinogen remaining stable during storage
AU705873B2 (en) Composition of tyrosine and polymerised allergen
US20100183659A1 (en) Allergen formulation
CN1260720A (en) Compositions useful as fibrin sealants
MXPA97008336A (en) Composition of tyrosine and allergen polymerize
JPS5822444B2 (en) Allergen Oyuusurutyrosinno Seizouhou
EP1325035B1 (en) Pharmaceutically acceptable starch and manufacturing process thereof
US20070142325A1 (en) Starch
JPH0667973B2 (en) Method for producing polymer particles containing amphipathic compound having ionogen group or reactive group implanted on the surface or latex comprising the particles
WO2022079678A1 (en) Method for the production of biocompatible nanomaterials with selective recognition capabilities and uses thereof
JPH05170655A (en) Virus inactivating agent and method for inactivating virus