# US 2023/0241184 A1 · Compositions and Methods for Treating Hemorrhagic Shock > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0241184 A1 - Document ID: US20230241184A1 - Status: Published application - Kind: A1 - Application number: 18/002,806 - Filed: 2021-06-23 - Published: 2023-08-03 - Earliest claimed: 2020-06-23 - Assignees: VirTech Bio, Inc. - Applicants: VirTech Bio, Inc - Inventors: William Richard Light, III - Web page: https://patentgrep.com/patent/US20230241184A1 ## CPC - A61K 38/42: Haemoglobins; Myoglobins - A61K 9/0026: {Blood substitute; Oxygen transporting formulations; Plasma extender} - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 35/16: Blood plasma; Blood serum (umbilical cord blood A61K35/51) - A61K 35/19: Platelets; Megacaryocytes - A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents - A61P 7/08: Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04) - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Pharmaceutical formulations to prevent or treat hemorrhagic shock are provided. The pharmaceutical formulations comprise an oxygenation complement comprising a hemoglobin-based oxygen carried (HBOC) and blood plasma. Related methods to prepare the pharmaceutical preparations are also provided. Furthermore, methods to prevent or treat hemorrhagic shock are provided. ## Claims ### Claim 1 A liquid pharmaceutical formulation comprising an oxygenation complement comprising a hemoglobin-based oxygen carrier (HBOC) and blood plasma. ### Claim 2 (depends on 1) The liquid pharmaceutical formulation according to claim 1, wherein the oxygenation complement comprises an HBOC quantity of from about 5% to about 95% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent. ### Claim 3 (depends on 1) The liquid pharmaceutical formulation according to claim 1, wherein the pharmaceutical formulation comprises: up to about 95% by weight of the oxygenation complement, the oxygenation complement comprising an HBOC quantity of from about 5% to about 95% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent; and the balance by weight of the pharmaceutical formulation being constituted by a pharmaceutically acceptable carrier, diluent, or auxiliary agent. ### Claim 4 (depends on 1) The liquid pharmaceutical formulation according to claim 1, wherein the oxygenation complement comprises an HBOC quantity of from about 5% to about 50% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent. ### Claim 5 (depends on 1) The liquid pharmaceutical formulation according to claim 1, wherein the pharmaceutical formulation comprises: up to about 95% by weight of the oxygenation complement, the oxygenation complement comprising an HBOC quantity of from about 5% to about 50% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent; and the balance by weight of the pharmaceutical formulation being constituted by a pharmaceutically acceptable carrier, diluent, or auxiliary agent. ### Claim 6 (depends on 1) The liquid pharmaceutical formulation according to claim 1, wherein the HBOC is a hyperpolymerized HBOC. ### Claim 7 (depends on 1) The liquid pharmaceutical formulation according to claim 1, wherein the auxiliary agent comprises blood platelets. ### Claim 8 A method for preventing or treating hemorrhagic shock, the method comprising intravenously administering to a subject in need thereof an effective amount of an oxygenation complement comprising a hemoglobin-based oxygen carrier (HBOC) and blood plasma, in an effective amount to prevent or treat hemorrhagic shock in the subject. ### Claim 9 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein the oxygenation complement is administered to the subject by consecutive administration of a liquid HBOC formulation and a liquid blood plasma formulation, wherein the liquid HBOC formulation is substantially free of blood plasma, and wherein the liquid blood plasma formulation is substantially free of HBOC. ### Claim 10 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein the oxygenation complement is administered to the subject by consecutive administration of the HBOC formulation and the blood plasma formulation, wherein the HBOC formulation is administered prior to the blood plasma formulation. ### Claim 11 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein the oxygenation complement is administered to the subject by consecutive delivery of the HBOC formulation and the blood plasma formulation, wherein the blood plasma formulation administered prior to the HBOC formulation. ### Claim 12 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein the HBOC formulation and the blood plasma formulation are administered to the subject no more than about 6 hours apart from each other. ### Claim 13 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein the oxygenation complement is administered by administering a liquid pharmaceutical formulation having been prepared by mixing an HBOC preparation and a blood plasma preparation. ### Claim 14 (depends on 13) The method for preventing or treating hemorrhagic shock according to claim 13, wherein the liquid pharmaceutical formulation further comprises a pharmaceutically acceptable carrier, diluent or auxiliary agent. ### Claim 15 (depends on 13) The method for preventing or treating hemorrhagic shock according to claim 13, wherein the oxygenation complement comprises an HBOC quantity of from about 5% to about 95% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent. ### Claim 16 (depends on 13) The method for preventing or treating hemorrhagic shock according to claim 13, wherein the liquid pharmaceutical formulation comprises up to 95% by weight of the oxygenation complement, the oxygenation complement comprising an HBOC quantity of from about 5% to about 95% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent; and the balance by weight of the pharmaceutical formulation being constituted by the pharmaceutically acceptable carrier, diluent, or auxiliary agent. ### Claim 17 (depends on 13) The method for preventing or treating hemorrhagic shock according to claim 13, wherein the oxygenation complement comprises an HBOC quantity of from about 5% to about 50% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent. ### Claim 18 (depends on 13) The method for preventing or treating hemorrhagic shock according to claim 13, wherein the liquid pharmaceutical formulation comprises up to 95% by weight of the oxygenation complement, the oxygenation complement comprising an HBOC quantity of from about 5% to about 50% by weight, and a blood plasma quantity of from about 5% to about 95% by weight, the HBOC and blood plasma quantities selected such that they together constitute less than 100% by weight of the oxygenation complement, the balance by weight of the oxygenation complement being constituted by a pharmaceutically acceptable diluent; and the balance by weight of the pharmaceutical formulation being constituted by the pharmaceutically acceptable carrier, diluent, or auxiliary agent. ### Claim 19 (depends on 16) The method for preventing or treating hemorrhagic shock according to claim 16, wherein the auxiliary agent comprises blood platelets. ### Claim 20 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein a pharmaceutical formulation comprising blood platelets is co-administered with the oxygenation complement. ### Claim 21 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein the hemorrhagic shock is caused by the subject having experienced traumatic blood loss. ### Claim 22 (depends on 8) The method for preventing or treating hemorrhagic shock according to claim 8, wherein the hemorrhagic shock is caused by the subject by having experienced non-traumatic blood loss. ### Claim 23 (depends on 1) A pharmaceutical package comprising (i) a first package comprising a hemoglobin-based oxygen carrier (HBOC) preparation and (ii) a second package comprising a blood plasma preparation, and instructions to prepare the liquid pharmaceutical formulation according to claim 1. ### Claim 24 (depends on 23) The pharmaceutical package according to claim 23, wherein the pharmaceutical package further comprises (iii) a third package comprising a pharmaceutically acceptable carrier, diluent or auxiliary agent for mixing with the HBOC preparation and the blood plasma preparation to thereby form the liquid pharmaceutical formulation. ### Claim 25 (depends on 23) The pharmaceutical package according to claim 23, wherein at least one of the HBOC preparation and the blood plasma preparation is a dried HBOC preparation or blood plasma preparation, having a moisture content from about 1% (w/w) to about 10% (w/w). ### Claim 26 (depends on 23) The pharmaceutical package according to claim 23, wherein the blood plasma preparation is a dried HBOC preparation having a moisture content from about 1% (w/w) to about 10% (w/w), and the HBOC preparation is a low ionic solute HBOC preparation. ### Claim 27 (depends on 26) The pharmaceutical package according to claim 26, wherein the low ionic solute HBOC preparation can comprise no more than about 13.5 mEq/L sodium ions (Na+), no more than about 0.35 mEq/L potassium ions (K+) ions, no more than about 0.46 mEq/L calcium ions (Ca2+), no more than about 0.15 mEq/L magnesium ions (Mg2+) ions, no more than about 9.6 mEq/L chloride ions (Cl−) ions, no more than 2.4 mEq/L bicarbonate ions (HCO32−), and no more than about 0.25 mEq/L hydrogen phosphate ions (HPO42−). ### Claim 28 (depends on 1) The method of preparing a liquid pharmaceutical formulation according to claim 1, the method comprising: mixing (i) a hemoglobin-based oxygen carrier (HBOC) preparation; and (ii) a blood plasma preparation; to thereby constitute an oxygenation complement or formulate a liquid pharmaceutical formulation. ### Claim 29 (depends on 28) The method of preparing a liquid pharmaceutical formulation according to claim 28, wherein the blood plasma preparation is a dried blood plasma preparation having a moisture content from about 1% (w/w) to about 10% (w/w), and the HBOC preparation is a liquid low ionic solute HBOC preparation. ### Claim 30 (depends on 29) The method of preparing a liquid pharmaceutical formulation according to claim 29, wherein the liquid HBOC preparation is a low ionic solute HBOC preparation comprising no more than about 13.5 mEq/L sodium ions (Na+), no more than about 0.35 mEq/L potassium ions (K+) ions, no more than about 0.46 mEq/L calcium ions (Ca2+), no more than about 0.15 mEq/L magnesium ions (Mg2+) ions, no more than about 9.6 mEq/L chloride ions (Cl−) ions, no more than 2.4 mEq/L bicarbonate ions (HCO32−), and no more than about 0.25 mEq/L hydrogen phosphate ions (HPO42−). ### Claim 31 (depends on 28) The A method of preparing a liquid pharmaceutical formulation according claim 28, wherein the method further comprises mixing (iii) a pharmaceutically acceptable carrier, diluent, or auxiliary agent together with the oxygenation complement to thereby form a liquid pharmaceutical formulation. ### Claim 32 (depends on 28) The method of preparing a liquid pharmaceutical formulation according to claim 28, wherein the HBOC preparation and the blood plasma preparation are mixed 1 hour or less prior to administration to a subject in need thereof. ### Claim 33 A liquid low ionic solute HBOC preparation comprising no more than about than about 27 milliequivalent (mEq/L) sodium ions (Na+), no more than about 0.7 mEq/L potassium ions (K+) ions, no more than about 0.92 mEq/L calcium ions (Ca2+), no more than about 0.3 mEq/L magnesium ions (Mg2+) ions, no more than about 19.2 mEq/L chloride ions (Cl−) ions, no more than 4.8 mEq/L bicarbonate ions (HCO32−), and no more than about 0.5 mEq/L hydrogen phosphate ions (HPO42−). ### Claim 34 (depends on 33) The liquid low ionic solute HBOC preparation according to claim 33, wherein the preparation comprises no more than about 13.5 mEq/L sodium ions (Na+), no more than about 0.35 mEq/L potassium ions (K+) ions, no more than about 0.46 mEq/L calcium ions (Ca2+), no more than about 0.15 mEq/L magnesium ions (Mg2+) ions, no more than about 9.6 mEq/L chloride ions (Cl−) ions, no more than 2.4 mEq/L bicarbonate ions (HCO32−), and no more than about 0.25 mEq/L hydrogen phosphate ions (HPO42−). ### Claim 35 (depends on 33) The liquid low ionic solute HBOC preparation according to claim 33, wherein the preparation comprises no more than about 6.75 mEq/L sodium ions (Na+), no more than about 0.175 mEq/L potassium ions (K+) ions, no more than about 0.23 mEq/L calcium ions (Ca2+), no more than about 0.075 mEq/L magnesium ions (Mg2+) ions, no more than about 4.8 mEq/L chloride ions (Cl−) ions, no more than 1.2 mEq/L bicarbonate ions (HCO32−), and no more than about 0.125 mEq/L hydrogen phosphate ions (HPO42−). ### Claim 36 (depends on 33, 34, 35) The liquid low ionic solute HBOC preparation according to any one of claims 33 to 35, wherein the low ionic solute HBOC preparation comprises an HBOC quantity of from about 5% to about 50% by weight, the balance of the preparation comprising a pharmaceutically acceptable diluent.