# US 10,478,404 B2 · Materials, methods and devices for altering cell reactivity > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,404 B2 - Document ID: US10478404B2 - Status: Granted - Kind: B2 - Application number: 15/113,393 - Filed: 2015-01-26 - Published: 2017-01-12 - Granted: 2019-11-19 - Earliest claimed: 2014-01-24 - Assignees: Arizona Board of Regents on Behalf of the University of Arizona - Applicants: The Arizona Board of Regents on behalf of The University of Arizona - Inventors: Marvin J. Slepian - Web page: https://patentgrep.com/patent/US10478404B2 ## CPC - A61K 31/10: Sulfides; Sulfoxides; Sulfones - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide - A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557) - A61K 31/337: having four-membered rings, e.g. taxol - A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine - A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol - A61K 31/685: one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin - A61K 35/19: Platelets; Megacaryocytes - C12N 5/0006: {Modification of the membrane of cells, e.g. cell decoration} - C12N 5/0644: {Platelets; Megakaryocytes} - C12N 2500/36: Lipids - C12N 2500/62: DMSO - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Methods, compositions, and devices to limit, modulate, insulate, and/or otherwise alter the effects of exogenous physical stimuli on cells are described herein. The cells may be removed from the body, preferably isolated, and treated ex vivo with the composition to limit the effects of physical stimuli on the cells and then returned to the patient. Alternatively, the cells may be treated in vivo. The compositions can be administered a variety of manners, such as systemically, locally or regionally. ## Claims ### Claim 1 An ex vivo or in vivo method of treating human cells to modulate their reactivity to exogenous physical forces comprising administering to human cells subjected to exogenous physical forces, a composition comprising an effective amount of one or more agents selected from the group consisting of: (i) a lipid or lipid related compound, hormone, carbachol, atropine, inositol, DMSO, lidocaine, procaine, sex steroids, phenytoin, perylene, 9-(dicyanovinyl) julodinine, 1,6-diphenyl-1,3,5-hexatiene (DPH), TMA-DPH, DPH-PA, cis and trans-parinaric acid, wherein the hormone is selected from the group consisting of cortisol, estradiol, progesterone, medroxyprogesterone, insulin, glucagon, thyroid hormone, and aldosterone; (ii) sulindac sulfide, phenolic antioxidants, caffeic acid phenethyl ester (CAPE) FAK signaling and modulating agents, resveratrol, Rho kinase inhibitors, Y-27632, inhibitors or modulators of talin, paxilin, and viculin and submembrane mechnotransductive proteins; (iii) cytochlasins, concanavalin, vincristine, vinblastine, oryzalin, trifluralin, taxol, and taxetere; (iv) colchicine, colcemid, 9 bromonscapine (EM011), docetaxel, noscapinoids, and tau; or (v) hypo or hypertonic solutions, saline, lactated ringers, dextrose, sucrose, and mannitol, aqueporin receptors modulating agents, Hg Cl2, G-protein modulating agents, tolvaptan, convivaptan, and vaptans wherein the exogenous physical force provides a shear stress greater than 50 dynes/cm2, wherein the method further comprising using a ventricular assist device (VAD) to pump blood in a patient's body, wherein the exogenous physical force is a force provided by the VAD. ### Claim 2 (depends on 1) The method of claim 1, wherein the lipid or lipid related compound is selected from the group consisting of fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipid, and prenol lipid. ### Claim 3 (depends on 1) The method of claim 1, wherein the cells comprise one or more of platelets, red blood cells, white blood cells, and circulating precursor and stem cells, and wherein the composition is applied to the cells. ### Claim 4 (depends on 1) The method of claim 1, wherein the shear force provides a shear stress of greater than or equal to about 1,000 dynes/cm2. ### Claim 5 (depends on 1) The method of claim 1, wherein the agent is selected from the group consisting of Ganglio sides, cholesterol, cholesterol hemisuccinate, lidocaine, procaine, sex steroids, phenytoin, Docohexanoic acid, PGE2, neuropeptide Y, polyunsaturated fatty acids, phosphatidyl choline, phosphatidylserine, phosphatidyl inositol, inositol, choline, cerebroside, glycosphingolipids, and sphingomyelin. ### Claim 6 (depends on 1) The method of claim 1, the force provides shear stress between a shear force of about 200 dynes/cm2 to a shear force of about 1000 dynes/cm2. ### Claim 7 (depends on 6) The method of claim 6, wherein the force provides shear stress of 500 dynes/cm2 or greater. ### Claim 8 An ex vivo or in vivo method of treating cells to modulate their reactivity to exogenous physical forces comprising administering to cells subjected to exogenous physical forces, a composition comprising an effective amount of one or more agents selected from the group consisting of: (i) carbachol, atropine, inositol, DMSO, lidocaine, procaine, sex steroids, phenytoin, perylene, 9-(dicyanovinyl) julodinine, 1,6-diphenyl-1,3,5-hexatiene (DPH), TMA-DPH, DPH-PA, cis and trans-parinaric acid; (ii) sulindac sulfide, phenolic antioxidants, caffeic acid phenethyl ester (CAPE) FAK signaling and modulating agents, resveratrol, Rho kinase inhibitors, Y-27632, inhibitors or modulators of talin, paxilin, and viculin and submembrane mechnotransductive proteins; (iii) cytochlasins, concanavalin, vincristine, vinblastine, oryzalin, trifluralin, taxol, and taxetere; (iv) colchicine, colcemid, 9 bromonscapine (EM011), docetaxel, noscapinoids, and tau; and (v) hypo or hypertonic solutions, saline, lactated ringers, dextrose, sucrose, and mannitol, aqueporin receptors modulating agents, agonists or antagonists, Hg Cl2, G-protein modulating agents, vasopressin receptors modulators, tolvaptan, convivaptan, and vaptans wherein the exogenous physical force provides a shear stress of about 200 dynes/cm2 or greater. ### Claim 9 An ex vivo or in vivo method of treating human cells to modulate their reactivity to exogenous physical forces comprising administering to human cells subjected to exogenous physical forces, a composition comprising an effective amount of one or more agents selected from the group consisting of: (i) a lipid or lipid related compound, carbachol, atropine, inositol, DMSO, lidocaine, procaine, sex steroids, phenytoin, perylene, 9-(dicyanovinyl) julodinine, 1,6-diphenyl-1,3,5-hexatiene (DPH), TMA-DPH, DPH-PA, cis and trans-parinaric acid; (ii) sulindac sulfide, phenolic antioxidants, caffeic acid phenethyl ester (CAPE) FAK signaling and modulating agents, resveratrol, Rho kinase inhibitors, Y-27632, inhibitors or modulators of talin, paxilin, viculin and submembrane mechnotransductive proteins; (iii) cytochlasins, concanavalin, vincristine, vinblastine, oryzalin, trifluralin, taxol, and taxetere; (iv) colchicine, colcemid, 9-bromonscapine (EM011), docetaxel, noscapinoids, and tau; (v) hypo or hypertonic solutions, saline, lactated ringers, dextrose, sucrose, and mannitol, aqueporin receptors modulating agents, agonists or antagonists, Hg Cl2, G-protein modulating agents, tolvaptan, convivaptan, and vaptans, and (v) a hormone selected from the group consisting of cortisol, estradiol, progesterone, medroxyprogesterone, insulin, glucagon, thyroid hormone, and aldosterone, wherein the exogenous physical force provides a shear stress of about 200 dynes/cm2 or greater, the method further comprising using a circulatory assist device to pump blood in a patient's body, wherein the circulatory assist device provides the exogenous physical force. ### Claim 10 (depends on 9) The method of claim 9, wherein the lipid or lipid related compound is selected from the group consisting of fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipid, and prenol lipid. ### Claim 11 (depends on 9) The composition of claim 9, wherein the agent is non-atherogenic cholesterol or DMSO. ### Claim 12 (depends on 9) The method of claim 9, wherein the cells comprise one or more of platelets, red blood cells, white blood cells, and circulating precursor and stem cells, and wherein the composition is applied to the cells. ### Claim 13 (depends on 9) The method of claim 9, wherein the force provides a shear stress of between 200 dynes/cm2 to about 1,000 dynes/cm2. ### Claim 14 (depends on 9) The method of claim 9, wherein the force provides a shear stress of up to about 1,000 dynes/cm2. ### Claim 15 (depends on 13) The method of claim 13, wherein the agent is selected from the group consisting of DMSO, non-atherogenic cholesterol, and taxel. ### Claim 16 (depends on 9) The method of claim 9, wherein the circulatory assist device is a VAD.