US5126147A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Sustained release dosage form
Assignee: BIOTECHNOLOGY MANAGEMENT ASSOCIATES Inc
•
Filing: 1990-02-08
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Granted: 1992-06-30
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Expires: 2010-02-08
Abstract
Abstract A multiphasic sustained release injectable delivery system is provided, as well as a method for treating humans and other mammals with that multiphasic sustained release system. The multiphasic sustained release system comprises prolonged, controlled delivery of microencapsulated macromolecular bioactive agent of biological origin comprising the bioactive agent encapsulated in microcapsules of bioerodible encapsulating polymer, which permits a sustained, multiphasic release of said bioactive agent, including (i) a first portion of said bioactive agent that upon injection is capable of being released from said microcapsules of bioerodible encapsulating polymer in a manner whereby only a relatively small amount of said bioactive agent is released during said first phase, whereby initial biological reaction is minimized due to said first portion producing a mild reaction similar to that normally observed with low doses of conventional administration; and (ii) secondary portions of said bioactive agent that provide a substantially higher level of bioactive agent in doses which could provoke a serious reaction in the patient, but for the prior release of said first portion.
Inventors
- 👤 Loui J. Silvestri
- 👤 H. Ruth Pyle
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 14:59
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5073; A61K9/5084
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
171 words
A multiphasic sustained release delivery system for prolonged, controlled delivery of microencapsulated macromolecular bioactive agent, comprising a macromolecular bioactive agent of a biological origin encapsulated in microcapsules of bioerodible encapsulating polymer, which permits a sustained, multiphasic release of said macromolecular bioactive agent, including: (i) a first portion of said macromolecular bioactive agent that upon injection is capable of being released from said microcapsules of bioerodible encapsulating polymer in a manner whereby only a relatively small amount of said macromolecular bioactive agent is released during a first phase, whereby initial biological reaction is minimized due to said first portion producing a mild local reaction similar to that normally observed with low doses of conventional administration; and (ii) a second portion of said macromolecular bioactive agent for release from said microcapsules after said initial biological reaction is minimized by said first portion to provide a substantially higher level of the macromolecular bioactive agent in doses which could provoke a serious reaction in the patient, but for the prior release of said first portion.
Claim 2
Dependent Claim
171 words
A multiphasic sustained release delivery system for prolonged, controlled delivery of microencapsulated macromolecular bioactive agent, comprising a macromolecular bioactive agent of a biological origin encapsulated in microcapsules of bioerodible encapsulating polymer, which permits a sustained, multiphasic release of said macromolecular bioactive agent, including: (i) a first portion of said macromolecular bioactive agent that upon injection is capable of being released from said microcapsules of bioerodible encapsulating polymer in a manner whereby only a relatively small amount of said macromolecular bioactive agent is released during a first phase, whereby initial biological reaction is minimized due to said first portion producing a mild local reaction similar to that normally observed with low doses of conventional administration; and (ii) a second portion of said macromolecular bioactive agent for release from said microcapsules after said initial biological reaction is minimized by said first portion to provide a substantially higher level of the macromolecular bioactive agent in doses which could provoke a serious reaction in the patient, but for the prior release of said first portion.
Claim 3
Dependent Claim
30 words
A multiphasic sustained release delivery system according to claim 1 wherein the macromolecular bioactive agent is selected from the group consisting of allergen-related substances, cytokines, anti-hemophilic factors and Receptor CD4.
Claim 4
Dependent Claim
35 words
A multiphasic sustained release delivery system according to claim 1 wherein the first and second portions of said macromolecular bioactive agent provide a controlled release providing a dosage profile having an accelerating or crescendoing release.
Claim 5
Dependent Claim
51 words
A multiphasic sustained release injectable delivery system for prolonged, controlled delivery of microencapsulated macromolecular bioactive agent in accordance with claim 1, wherein the harmful effects of the released macromolecular bioactive agents are controlled by the synchronous release of an agent for symptomatic treatment of initial adverse reactions to the initial dose.
Claim 6
Dependent Claim
28 words
A multiphasic sustained release injectable delivery system of claim 4 wherein said agent for symptomatic treatment comprises a non-steroidal anti-inflammatory agent, an anti-histamine, a corticosteroid, or a bronchodilator.
Claim 7
Dependent Claim
62 words
A multiphasic sustained release injectable delivery system for prolonged, controlled delivery of microencapsulated macromolecular bioactive agent of claim 1, wherein said bioerodible encapsulating polymer is a member selected from the group of poly(lactides), poly(glycolides), and copolymers and derivatives thereof; non-peptide polyamino acids; poly (ortho esters); low and high molecular weight polyanhydrides; polyiminocarbonates; poly alpha-aminoacids; polyalkyl-cyano-acrylate; polyphosphazenes; and acyloxymethyl polyaspartate and polyglutamate copolymers.
Claim 8
Dependent Claim
68 words
A multiphasic sustained release injectable delivery system for prolonged, controlled delivery of microencapsulated bioactive agent of claim 1, wherein the multiphasic release rate is achieved by providing a mixture of microspheres, those corresponding to said first portion (i) including hydrolysis retarding agents impregnated in the microsphere polymer layers, while the microspheres corresponding to said second portion (ii) either contain hydrolysis accelerating agents, or no accelerating agent at all.
Claim 9
Dependent Claim
35 words
A multiphasic sustained release injectable delivery system of claim 7 wherein said hydrolysis retarding and accelerating agents are non-toxic organic acids or bases, or an acidic, neutral or basic inorganic salt, or a solution thereof.
Claim 10
Dependent Claim
63 words
A multiphasic sustained release injectable delivery system for prolonged, controlled delivery of microencapsulated bioactive agent of claim 1, wherein the multiphasic release rate is achieved by providing a mixture of microspheres, those corresponding to said first portion (i) may include no hydrolysis retarding agents impregnated in the microsphere polymer layers, while the microspheres corresponding to said second portion (ii) contain hydrolysis accelerating agents.
Claim 11
Dependent Claim
35 words
A multiphasic sustained release injectable delivery system of claim 9 wherein said hydrolysis retarding and accelerating agents are non-toxic organic acids or bases, or an acidic, neutral or basic inorganic salt, or a solution thereof.
Claim 12
Dependent Claim
21 words
A multiphasic sustained release injectable delivery system of claim 1 wherein a stabilizing agent is encapsulated along with the bioactive agent.
Claim 13
Dependent Claim
20 words
A multiphasic sustained release injectable delivery system of claim 11 wherein said stabilizing agent is the thermopreservative glycerine or mannitol.
Claim 14
Dependent Claim
20 words
A multiphasic sustained release injectable delivery system of claim 1 wherein an adjuvant is encapsulated along with the bioactive agent.
Claim 15
Dependent Claim
21 words
A multiphasic sustained release injectable delivery system of claim 13 wherein said adjuvant is tyrosine, polytyrosine, dimethylglycine (DMG), or muramyl dipeptide.
Claim 16
Dependent Claim
19 words
A multiphasic sustained release injectable delivery system of claim 1 wherein the encapsulated bioactive agent is in aqueous form.
Claim 17
Dependent Claim
19 words
A multiphasic sustained release injectable delivery system of claim 1 wherein the encapsulated bioactive agent is in lyophilized form.
Claim 18
Dependent Claim
20 words
A multiphasic sustained release injectable delivery system of claim 1 wherein the macromolecular bioactive agent is unextracted allergen source material.
References Cited (Backward Citations)
US3429827A
Cited
US4226853A
Cited
US3794630A
Cited
US3825525A
Cited
US3893993A
Cited
US3903067A
Cited
US3761585A
Cited
US3792159A
Cited
US4180562A
Cited
US4351337A
Cited
US3976071A
Cited
US4070455A
Cited
US3978203A
Cited
US4131648A
Cited
US4093709A
Cited
US4261973A
Cited
US4158705A
Cited
US4140679A
Cited
US4164560A
Cited
US4256732A
Cited
US4215036A
Cited
US4222907A
Cited
US4234569A
Cited
US4269764A
Cited
US4338297A
Cited
US4439199A
Cited
US4469677A
Cited
US4609547A
Cited
US4675189A
Cited
US4767628A
Cited
US4767628B1
Cited
US4428932A
Cited
US4479911A
Cited
US4526938A
Cited
US4675381A
Cited
US4781919A
Cited
US4683288A
Cited
US4774074A
Cited
US4757128A
Cited
US4861627A
Cited
US4994279A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-06-30 | 1995-12-30 | 1996-06-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-06-30 | 1999-12-30 | 2000-06-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-06-30 | 2003-12-30 | 2004-06-30 | $7700.00 | Window Closed / Lapsed |