CN1183046A - Composition of tyrosine and polymerised allergen - Google Patents
Composition of tyrosine and polymerised allergen Download PDFInfo
- Publication number
- CN1183046A CN1183046A CN96193592A CN96193592A CN1183046A CN 1183046 A CN1183046 A CN 1183046A CN 96193592 A CN96193592 A CN 96193592A CN 96193592 A CN96193592 A CN 96193592A CN 1183046 A CN1183046 A CN 1183046A
- Authority
- CN
- China
- Prior art keywords
- tyrosine
- anaphylactin
- solution
- compositions
- allergen
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/35—Allergens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/35—Allergens
- A61K39/36—Allergens from pollen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Abstract
A pharmaceutical composition comprising tyrosine and a polymerised allergen is prepared by (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.
Description
The present invention relates to be used for the new compositions of anaphylaxis patient's desensitization treatment.
GB-A-1492973 has described and has prepared a kind of method that is dispersed with the tyrosine coprecipitate of modification anaphylactin.This anaphylactin has used a kind of reagent (for example glutaraldehyde) to handle and modification, makes interior molecules crosslinked and reduced the anaphylaxis of product with respect to unmodified anaphylactin.
People such as EP-A-0367306 and Nakada (Allergy, 54[1985] 437 et seq.) has described the method for preparing polymeric anaphylactin.Thereby these methods are prolongations makes intermolecular cross-linking with the cross-linking agent processing time, and then unpolymerized product is removed in filtration or dialysis.This polymeric anaphylactin has hypoallergenic.
The invention provides a kind of pharmaceutical composition that contains tyrosine and polymerised allergen.This anaphylactin is for example used coprecipitation method usually with the tyrosine coating or be adsorbed on the tyrosine.
This anaphylactin can cause that material hypersensitive derives from any, for example from pollen (as Ambrosia or Betula pollen), food, insecticide venom, mycete, and animal skin, or house dust small worm (D.farnae or dermatophagoides pteronyssinus (D.pteronyssinus)).This anaphylactin is particularly deutero-from D.pteronyssinus.Here said " anaphylactin " comprises it can being single source or more than a kind of anaphylactin mixture of source.
Another aspect of the present invention provides the method for preparing pharmaceutical composition of the present invention, this method comprises: (a) with the anaphylactin polymerization, (b) aqueous solution of this anaphylactin is mixed with tyrosine solution in moisture strong acid, (c) with this solution mixture neutralization, make tyrosine and polymerised allergen co-precipitation therefrom and (d) randomly this product is mixed with the physiology acceptable carrier.
Suitable physiology acceptable carrier comprises phenol saline and sterilized water.
By at pH3-10, general 7 ± 1 and 0-100 ℃, under general 4-37 ℃ the temperature, reach 10 hours with dialdehyde (for example glutaraldehyde) processing, for example at room temperature handled about 2 hours, with this anaphylactin polymerization.The ratio of anaphylactin and glutaraldehyde generally is 1: 25-1: 2 scope, for example about 1: 4 (w/w), but can use higher anaphylactin ratio (for example seeing EP-A-0367306) with the longer response time, it is about 7 hours that the document has been used about 3: 1 ratio and response time).
By gel filtration or dialysis, low molecular weight product is removed in for example slipstream dialysis then.This product lyophilization or be directly used in next stage.Molecular weight is generally limit at least 100 kilodaltons, for example at least 250 kilodaltons, more preferably 300 kilodaltons.
Then, with obtain as reactant mixture in the polymerization process or to be 7 ± 1 polymerised allergen solution from the pH that solid solvation obtains mix with tyrosine solution moisture strong acid.This strong acid is mineral acid normally, preferred hydrochloric acid.The anaphylactin albumen that generally contains 0.1 μ g/ml-100 μ g/ml at the polymerised allergen solution of this step use.Anaphylactin in this mixture: the ratio of tyrosine is generally 1: 4 * 10
5-1: 4 * 10
2Scope (w/w).
The mixture of resulting anaphylactin and tyrosine solution neutralizes." neutralization " is meant pH regulator in the scope of 4.0-7.5.Importantly, during neutralizing, the pH of this solution can not or can not be elevated to more than 7.5 in for a long time any time at least significantly.By stirring this solution tempestuously, and if desired, can satisfy this condition by the alkali that only uses requirement.Various buffer agents can be joined in the anaphylactin solution effectively, mix and neutralization stage control pH so that help.
Carrying out neutral useful especially method is that tyrosine solution and neutralization bases liquid stream in acid are separately flow in the solution of anaphylactin.With the speed of pH control adding liquid stream, promptly regulate the flow of one or two solution by an equipment, cause the pH of reactant mixture to be substantially constant on the scheduled volume.We find, by obtaining optimum usually in the scope that pH is controlled at 6.5-7.5, although accurate pH can change according to the character of anaphylactin.
Neutral result is that the anaphylactin solution that is mingled with in tyrosine and/or adsorbs on tyrosine precipitates immediately.Post precipitation perhaps washs this mixture immediately, perhaps allows it leave standstill several hours-1 or 2 day time before washing.Preferably obtain thin as far as possible precipitate, this can realize by cooperating vigorous stirring and quick this solution of neutralization.
Thereby it is resuspended in the physiology acceptable carrier for example produce in phenol saline or the sterilized water be applicable to the injectable compositions of desensitization treatment before, by centrifugalize or filtration and washing (for example using phenol saline), can from solution, isolate resulting precipitation.
The following examples explanation the present invention.
Embodiment
With by dialysis or fractional distillation and the D.pteronyssinus of partially purified about 2.5mg/ml extracts proteic neutral solution by adding isopyknic 1% (w/v) glutaraldehyde and making its polymerization in about 2 hours at this mixture of stirring at room.This reaction is by adding isopyknic 2% (w/v) glycine and at room temperature this mixture restir being made reaction stop in 1 hour.Remove by filter low molecular weight substance by the film dialysis that can get rid of 300 kilodalton molecular weight.Then with this mixture filtration sterilization and lyophilization.
Perhaps, perhaps, prepare this polymerised allergen solution again by this cryodesiccated solid directly from the solution of sterilising filtration.This solution contains 10 μ g/ml in the phosphate buffer of pH7 ± 1.Under vigorous stirring, simultaneously L-tyrosine (by L-tyrosine with 24g with 3.4M HCl be dissolved into 100ML preparation) and the 3.2M NaOH of 1 volume of 1 volume in HCl joined in the anaphylactin solution of 4 volumes, make this anaphylactin solution and tyrosine co-precipitation.Form suspension like this, centrifugalize, repeatedly wash, so that remove impurity and resuspending in the buffer saline of pH6 ± 1 of beginning volume with buffer saline.
Claims (7)
1. pharmaceutical composition that contains tyrosine and polymerised allergen.
2. according to the compositions of claim 1, wherein this anaphylactin is with the tyrosine coating and/or be attracted on the tyrosine.
3. according to the compositions of claim 1 or 2, wherein this anaphylactin is deutero-from dermatophagoides pteronyssinus.
4. method for preparing the pharmaceutical composition of aforementioned arbitrary claim, this method comprises: (a) with the anaphylactin polymerization, (b) aqueous solution of this anaphylactin is mixed with tyrosine solution in moisture strong acid, (c) with this solution mixture neutralization, make tyrosine and polymerised allergen co-precipitation therefrom and (d) randomly this product is mixed with the physiology acceptable carrier.
5. the compositions of arbitrary claim among the claim 1-3 that is used for the treatment of.
6. according to the compositions of arbitrary claim among the claim 1-3, be used for anaphylaxis patient's desensitization treatment.
7. the compositions of arbitrary claim is used for the purposes of the medicine of anaphylaxis patient desensitization treatment among the claim 1-3 in preparation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9508785.4A GB9508785D0 (en) | 1995-04-29 | 1995-04-29 | Novel compositions |
| GB9508785.4 | 1995-04-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1183046A true CN1183046A (en) | 1998-05-27 |
| CN1132629C CN1132629C (en) | 2003-12-31 |
Family
ID=10773769
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96193592A Expired - Lifetime CN1132629C (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) | NO974893D0 (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) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103608034A (en) * | 2011-04-21 | 2014-02-26 | 过敏疗法（英国）有限责任公司 | Process for preparing vaccine composition |
Families Citing this family (3)
| 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 |
Family Cites Families (4)
| 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. |
-
1995
- 1995-04-29 GB GBGB9508785.4A patent/GB9508785D0/en active Pending
-
1996
- 1996-04-25 KR KR1019970707645A patent/KR19990008120A/en not_active Application Discontinuation
- 1996-04-25 BR BR9608123A patent/BR9608123A/en not_active Application Discontinuation
- 1996-04-25 AU AU57616/96A patent/AU705873B2/en not_active Expired
- 1996-04-25 PL PL96323104A patent/PL183484B1/en unknown
- 1996-04-25 TR TR97/01265T patent/TR199701265T1/en unknown
- 1996-04-25 SK SK1461-97A patent/SK281877B6/en not_active IP Right Cessation
- 1996-04-25 HU HU9802237A patent/HUP9802237A3/en unknown
- 1996-04-25 WO PCT/EP1996/001733 patent/WO1996034626A1/en not_active Application Discontinuation
- 1996-04-25 EA EA199700271A patent/EA199700271A1/en unknown
- 1996-04-25 CZ CZ19973429A patent/CZ288401B6/en not_active IP Right Cessation
- 1996-04-25 CN CN96193592A patent/CN1132629C/en not_active Expired - Lifetime
- 1996-04-25 JP JP8532981A patent/JPH11504338A/en active Pending
- 1996-04-25 CA CA002217388A patent/CA2217388A1/en not_active Abandoned
- 1996-04-25 EP EP96914124A patent/EP0825874A1/en not_active Withdrawn
- 1996-04-25 NZ NZ308080A patent/NZ308080A/en not_active IP Right Cessation
- 1996-04-26 ZA ZA963340A patent/ZA963340B/en unknown
-
1997
- 1997-10-23 NO NO974893A patent/NO974893D0/en not_active Application Discontinuation
- 1997-10-29 BG BG102004A patent/BG63990B1/en unknown
-
1998
- 1998-11-20 HK HK98112143A patent/HK1010834A1/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103608034A (en) * | 2011-04-21 | 2014-02-26 | 过敏疗法（英国）有限责任公司 | Process for preparing vaccine composition |
| CN103608034B (en) * | 2011-04-21 | 2017-10-10 | 过敏疗法（英国）有限责任公司 | Method for preparing vaccine combination |
Also Published As
| Publication number | Publication date |
|---|---|
| BR9608123A (en) | 1999-02-09 |
| HK1010834A1 (en) | 1999-07-02 |
| BG102004A (en) | 1998-11-30 |
| PL323104A1 (en) | 1998-03-16 |
| SK281877B6 (en) | 2001-08-06 |
| HUP9802237A2 (en) | 1999-02-01 |
| PL183484B1 (en) | 2002-06-28 |
| SK146197A3 (en) | 1998-05-06 |
| HUP9802237A3 (en) | 2000-06-28 |
| CZ288401B6 (en) | 2001-06-13 |
| WO1996034626A1 (en) | 1996-11-07 |
| AU5761696A (en) | 1996-11-21 |
| GB9508785D0 (en) | 1995-06-21 |
| CN1132629C (en) | 2003-12-31 |
| CA2217388A1 (en) | 1996-11-07 |
| EP0825874A1 (en) | 1998-03-04 |
| NO974893L (en) | 1997-10-23 |
| TR199701265T1 (en) | 1998-02-21 |
| NZ308080A (en) | 1999-05-28 |
| ZA963340B (en) | 1997-03-27 |
| JPH11504338A (en) | 1999-04-20 |
| AU705873B2 (en) | 1999-06-03 |
| KR19990008120A (en) | 1999-01-25 |
| BG63990B1 (en) | 2003-09-30 |
| NO974893D0 (en) | 1997-10-23 |
| CZ342997A3 (en) | 1998-03-18 |
| EA199700271A1 (en) | 1998-04-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CX01 | Expiry of patent term |
Granted publication date: 20031231 |
|
| EXPY | Termination of patent right or utility model |