Methods of administering microencapsulated materials for immune modulated diseases
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/50
A61K-038/16
A61K-039/395
출원번호
US-0740755
(1996-11-01)
발명자
/ 주소
D'Souza,Martin J.
Oettinger,William Carl
Oliver,James Cameron
출원인 / 주소
The Corporation of Mercer University
대리인 / 주소
Powell Goldstein LLP
인용정보
피인용 횟수 :
3인용 특허 :
4
초록▼
Compositions useful in treating immune modulated disease comprising an anticytokine antibody or immune active drug capable of modifying cytokine activity or modulating the immune system microencapsulated with a biodegradable nonantigenic material, such as albumin or PLGA. When the composition is int
Compositions useful in treating immune modulated disease comprising an anticytokine antibody or immune active drug capable of modifying cytokine activity or modulating the immune system microencapsulated with a biodegradable nonantigenic material, such as albumin or PLGA. When the composition is introduced into a subject, it is phagocytosed by the target organ, the target organ digests the microsphere, releasing the drug or an active form or fragment thereof intracellularly. The drug then modifies the target organ function, thereby modulating it's activity. A method is disclosed for preparation of the microencapsulated composition.
대표청구항▼
We claim: 1. A method of administering a substance to a subject having an immune modulated disease, comprising the steps of: (a) preparing a microencapsulated composition, comprising the steps of i) providing an aqueous phase of a solubilized amount of an antibody or protein material to be encapsul
We claim: 1. A method of administering a substance to a subject having an immune modulated disease, comprising the steps of: (a) preparing a microencapsulated composition, comprising the steps of i) providing an aqueous phase of a solubilized amount of an antibody or protein material to be encapsulated, said material being solubilized in phosphate buffered saline; ii) mixing said solubilized material with an amount of biodegradable and nonantigenic albumin dissolved in water or phosphate buffered saline to form an aqueous phase mixture; iii) adding said aqueous phase mixture of step ii) to an amount of olive oil; iv) emulsifying said aqueous phase mixture formed in step iii) to form microspheres of encapsulated material; and, v) contacting said encapsulated microspheres with a crosslinking agent for a time sufficient to crosslink at least a portion of said microspheres, such that said crosslinked microspheres have bioactivity and such that denaturization is substantially prevented; and, b) administering to said subject a therapeutically effective amount of said crosslinked microspheres. 2. The method of claim 1, further comprising after step (a) (ii) and before step (a) (iii), the step (a)(vi) cooling said mixture of step (a)(ii). 3. The method of claim 2, further comprising step (a)(vii) cooling and maintaining said oil of step (a)(iii) at a cooled temperature prior to the addition of said aqueous phase mixture of step (a)(ii). 4. The method of claim 3, wherein said cooling of said olive oil is 5째 C. 5. The method of claim 3, further comprising after step (a)(v) the step (a)(viii) washing said microspheres. 6. The method of claim 5, further comprising after step (a) (viii) the step (a)(ix) sizing said washed microspheres. 7. The method of claim 1, wherein said material is selected from the group consisting of polyclonal antibodies, monoclonal antibodies, and mixtures thereof. 8. The method of claim 1, wherein said material comprises an antibody to a material selected from the group consisting of TNF-alpha and interleukin-1 receptor antagonist. 9. The method of claim 1, wherein said material comprises a neutralizing antibody to a cytokine. 10. The method of claim 9, wherein said neutralizing antibody is selected from the group consisting of antibodies to TNF-alpha, IL-1β, IL-6, IL-8, and IL-1RA. 11. The method of claim 1, wherein said microspheres have an average diameter of from about 0.22 micron to about 10 microns. 12. The method of claim 1, wherein said microspheres have an average diameter of from about 0.22 micron to about 0.8 microns. 13. The method of claim 1, wherein said mixture is emulsified by sonification. 14. The method of claim 1, wherein said crosslinking agent is glutaraldehyde. 15. A method of administering a substance to a subject having an immune modulated disease, comprising the steps of: a) preparing a microencapsulated composition, comprising the steps of: i) providing a material comprising an anticytokine neutralizing antibody or mixture of anticytikine neutralizing antibodies that has been solubilized in phosphate buffered saline (PBS) to form an aqueous mixture; ii) mixing said solubilized material with an amount of biodegradable and nonantigenic albumin dissolved in water or PBS to form an aqueous mixture; iii) adding said aqueous phase mixture of step ii) to an amount of olive oil in a hydrophobic phase; iv) emulsifying said aqueous phase mixture formed in step iii) by sonification to form microspheres of encapsulated material; and, v) contacting said encapsulated microspheres with an amount of glutaraldehyde for a time sufficient to crosslink at least a portion of said microspheres; vi) washing said microspheres; vii) sizing said microspheres such that said crosslinked microspheres have bioactivity and such that denaturization is substantially prevented; and b) administering said crosslinked microspheres to a subject such that said encapsulated microspheres are engulfed by a target organ, resulting in the intracellular release of said material.
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이 특허에 인용된 특허 (4)
Eppstein Deborah A. (Palo Alto CA) Schryver Brian B. (Redwood City CA), Controlled release of macromolecular polypeptides.
Illum Lisbeth (Nottingham GBX), Enhanced uptake drug delivery system having microspheres containing an active drug and a bioavailability improving mater.
Le Junming ; Vilcek Jan ; Dadonna Peter ; Ghrayeb John ; Knight David ; Seigal Scott, Methods of treating TNF.alpha.-mediated disease using chimeric anti-TNF antibodies.
DeLuca Patrick P. (Lexington KY) Kanke Motoko (Fukuyama JPX) Sato Toyomi (Tokyo CA JPX) Schroeder Hans G. (Encinitas CA), Porous microspheres for drug delivery and methods for making same.
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