Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1995-04-14
1998-08-11
Clardy, S. Mark
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424490, A61K 951
Patent
active
057924759
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a lymphatic delivery composition, and more particularly to a composition for delivering an active agent to the lymphatic system.
The lymphatic system has an important role in transporting body fluids and particulate materials to include proteins, fat particles, etc. Large proteins and certain cells (lymphocytes) pass from the blood plasma into the tissue fluid and it is the major function of the lymph to return these essential components to the blood circulation. The lymph also plays an important role in transporting the products of fat digestion in the gastrointestinal tract, the chylomicrons, into the blood circulation. The properties of the lymphatic system have been reviewed in detail by J. M. Yoffrey and F. C. Courtice (Lymphatics, lymph and the lymphomyeloid complex, Academic Press, London, 1970). The lymphatic system also plays and important role in the spread of tumours. Malignant cells can enter the lymphatic system and become captured by lymph nodes where secondary tumours can be produced. Eventually the whole of the lymph chain can be involved. The lymph can also be involved in the spread of tumours to other organs, for example the lungs. Consequently there is considerable need for a method of examining the lymphatic drainage and lymph nodes in the diagnosis and treatment of malignant diseases. This subject has been reviewed extensively by S. E. Strand and others (L. Bergquist et al. in Microspheres and Drug Therapy, Immunological and Medical Aspects p.263 (Edited by Davis et al.) Elsevier 1984).
It is well known that colloidal particles can have an important role in characterising the properties of the lymphatic system as well as a possible role in delivering drugs to the lymphatic system. The use of colloidal particles as radiodiagnostic agents has been reviewed by Strand et al. (Bergquist et al. Seminars in Nuclear Med. 12 (1983) 9-19). A wide range of materials has been examined to include solid particles, emulsions and vesicles (liposomes). The distribution of colloidal agents depends strongly on their particle size and colloids suggested for lymphoscintigraphy were found to have a median size of about 40-60 nm. Uptake into regional lymph nodes after, for example, subcutaneous administration is quite small and values from 1-10% are typical after 2-5 hours (Strand, S. E. CRC Crit. Rev. Drug Carrier System 6 (1989) 211-237).
A targeting system for the delivery of diagnostic and therapeutic agents to the lymphatic system should have the following characteristics: nodes.
Various attempts have been made to increase lymphatic uptake by change in particle size and particle number and particle nature and these have been reviewed by Strand (CRC Crit. Rev. Drug Carrier Systems 6 (1989) 211-237). With liposome systems the best recorded level of uptake in the lymph nodes is from 1-2% at 48 hours. This can be increased to about 5% by the attachment of antibodies. (Patel, H. M. In Liposomes as drug carriers, Ed. G. Gregoriadis, p.51 John Wiley, 1988, Kaledin, J. et al. Nat. Cancer Inst. 69 (1982) 67-71, Turner, A. et al. Biochim. Biophy. Acta 760 (1983) 119-125).
GB 2108967 describes the admixture of colloidal albumin particles with poloxamers and ethoxylated surfactant of the Cremophor series and measurements and lymphatic uptake are described. The quantities sequestered in lymph nodes are reported for times of 2 hours after administration. For the poloxamer materials only the hydrophilic materials containing 80% ethylene oxide content were examined. The uptake in the primary lymph nodes was increased with values as high as 17% reported for Poloxamer 238. For Poloxamer 188 about 13% of the colloid was captured in the primary nodes. However, only 1% was reported to be found in the secondary nodes.
High uptake into both primary and secondary lymph nodes has not been achieved and this is a big disadvantage for delivery of diagnostic and therapeutic agents to the lymphatic system.
Illum and others have described the use of surfactants and in particular the poloxamers and pol
REFERENCES:
patent: 4904479 (1990-02-01), Illum
Journal of Colloid and Interface Science, vol. 136, No. 2, 1990, pp. 415-431, J.S. Tan et al. "Protein Adsorption and Conformational Change on Small Protein Particles."
Internat'l J. of Pharmaceutics, vol. 67, No. 1, 1991 pp. 29-37, H. Carstensen et al. "Adsorption of Ethoxylated Surfactants on Nanoparticles, Interaction Chromatography."
Journal of Controlled Release, vol. 25, No. 1/2, 27 May 1993, pp. 123-132, S. Rudt et al., "In Vitro Phagocytosis Assay of Nano-and Microparticles by Chemiluminescense. IV. Effect of Surface Modification by Coating of Particles with Poloxamine and Antarex CO on the Phagocytic Uptake."
Allen, et al., "Subcutaneous Administration Of Liposomes: A Comparison With The Intravenous And Intraperitoneal Routes Of Injection", Bioch. et Bio. Acta, 1150:9-16 (1993).
Bergquist, et al., "Particle Sizing And Biokinetics Of Interstitial Lymphoscintigraphic Agents", Nuclear Med., 12:9-19 (1983).
Bergquist, et al., "The Characterization Of Radiocolloids Used For Administration To The Lymphatic System", In Microspheres And Drug Therapy Immunological And Medical Aspects, p. 263 (Davis et al., Eds.) Elsevier Science Publishers, 1984.
Christy, et al., "Effect Of Size On The Lymphatic Uptake Of A Model Colloid System", Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 19 (1992).
Cogrove, et al., "An Experimental Study Of Polymer Conformations At The Solid/Solution Interface", In Adsorption From Solution, Eds., Ottewill et al. Eds., Academic Press 1983.
Costello, et al., "Investigations Of The Properties Of Aqueous Sterically Stabilized Dispersions", J. Colloid Interface Sci., 152:237 (1992).
Harris, et al., "Determination Of The Adsorption Of Surface Active Agents By Small Angle Scattering", In Adsorption From Solution, Eds., Ottewill et al. pp. 287-297, Academic Press 1983.
Huh, et al., A Radiation-Induced Bonding Of Iodine At The Surface Of Uniform Polystyrene Particles, Radiation Res., 60:42-53 (1974).
Kaledin, et al., "Subcutaneoulslsly Injected Radiolabeled Liposmomomes: Transport To The Lymph Nodes In Mice", Nat. Cancer Inst., 69:67-71 (1982).
Kayes & Rawlins, Adsorption Characteristics Of Certain Polyoxyethylene-Polyoxypropylene Block Co-Polymers On Polystyrene Latex`, Colloid Polymer Sci., 257:622-629 (1979). H!methotrexate-encapsulated Neutral Large Unilamellar Vesicles And Immunoliposomes", International J. Pharmaceutics, 98:9-18 (1993).
Litzinger & Huang, "Amphipathic Poly(ethylene glycol) 5000-Stabilized Dioleoylphosphatidylethanolamine Liposomees Accumulate In Spleen", Biochim. Biophys. Acta., 1127:249 (1992).
Mangat & Harish, "Lymph Node Localization Of Non-Specific Antibody-Coated Liposomes", Life Science, 36:1917-1925 (1985).
Maas, et al., "Ultrasmall Magnetite Particles Coated With Polyethylenglycol As Contrast Agent In MRI Of Experimental Abscesses: An Animal Study In Mini-Pigs", Abstracts 10th Meeting: Society Of Magnetic Resonance In Medicine, vol. 2 (1991).
Muller, et al., "Surface Characterization Of Colloidal Drug Carriers For Drug Targeting By Aqueous Two-Phase Partitioning", Application In Cell Biology And Biotechnology, Eds. Fisher et al., Plenum Press, New York, 149-155 (1989).
Muller, et al., "Particle Charge And Surface Hydrophobicity Of Colloidal Drug Carriers", Targeting Of Drugs With Synthetic Systems, Eds. Gregoriadis et al., Plenum, New York, 239-263 (1986).
Osborne, et al., "Radionuclide-Labelled Liposomes--A New Lymph Node Imaging Agent", International J. Nucl. Med. Biol., 6:75-83 (1979).
Ottewill, et al., "Non-Ionic Polystyrene Latices In Aqueous Media", Br. Polym J., 19:435-440 (1987).
Patel, "Fate Of Liposomes In the Lymphatics", Liposomes As Drug Carriers, G. Gregoriadis, Ed., John Wiley, 51-61 (1988).
Perez-Soler, et al., "Distribution Of Radiolabeled Multilamellar Liposomes Injected Intralymphatically And Subcutaneously", Int. J. Nucl. Med. Biol., 12(4):261-266 (1985).
Prestidge & Tadros "Viscoelastic Properties Of Aqueous Concentrated Polystyrene Latex
Christy Nicola
Davis Stanley S.
Illum Lisbeth
Moghimi Moein
Clardy S. Mark
Danbiosyst UK Limited
Harrison Robert H.
LandOfFree
Lymphatic delivery composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Lymphatic delivery composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Lymphatic delivery composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-386699