Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
  • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
  • A61K35/14—Blood; Artificial blood
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F13/00—Bandages or dressings; Absorbent pads
  • A61F13/00987—Apparatus or processes for manufacturing non-adhesive dressings or bandages
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/02—Inorganic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
  • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
  • A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
  • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
  • A61L15/42—Use of materials characterised by their function or physical properties
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
  • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2400/00—Materials characterised by their function or physical properties
  • A61L2400/04—Materials for stopping bleeding

Definitions

• the present disclosure is in the field of preparation of medical treatment, in particular preparation of a coagulated blood mass for use in a treatment of a subject.
• the present disclosure provides a method, a coagulation mold and a kit for preparing a coagulated blood mass, namely blood clot having a desired shape and volume.
• the coagulated blood mass is prepared from whole blood being withdrawn from a subject.
• the whole blood is mixed with coagulation initiators, i.e. coagulation agents or anti-anti coagulation agents, in a specific amount and having specific characteristics in order to obtain the coagulated blood mass with optimal parameters, such as stability, moisture, homogeneousness, namely the texture of the clot is substantially similar at any portion thereof, etc.
• Another parameter to yield the desired coagulated blood mass of the present invention is the selected amount of material of coagulation initiator to be mixed with the whole blood.
• a first aspect of the present disclosure provides a method for preparing a coagulated blood mass, i.e. a volumetric blood clot, for use in a treatment of a lesion or injury of a subject.
• the treatment can be on the external portion of the body such as skin lesions or on internal portions of the body such as fistula cavity, abdominal cavity, etc.
• the method comprising: mixing an amount of whole blood with calcium gluconate powder and kaolin powder; and allowing the whole blood to coagulate to form the coagulated blood mass.
• the term "allowing" defines that the mixture of blood with maintaining the mixture of whole blood with calcium gluconate powder and kaolin powder is maintained for a selected amount of time until the blood solidifies to a certain degree and seize to be in a flowable form.
• the amount of time can be more than 1 minute, 2, 3, 4, 5, 6, 7, 8, 9, 10 or even more than 15 minutes until the whole blood is solidified to the desired degree.
• the method is further characterized by at least one of: (i) the particle-size distribution D50 of the calcium gluconate powder is between 50g-200g, (ii) wherein said mixing comprises mixing between 0.6 mg - 3.1 mg of kaolin powder with every 1 ml of whole blood, (iii) wherein said mixing comprises mixing between 2.5 mg - 8.1 mg of calcium gluconate powder with every 1 ml of whole blood, or (iv) the particle - size distribution D50 of the kaolin powder is less than 20LI.
• the particle-size distribution DX means that X% of the particles in the powder are less than the nominal size associated with said distribution. For example, if the particle-size distribution D50 is 125g then 50% of the particles are having a volumetric size equal or less to 125g.
• the resulted coagulated blood mass is homogenous, namely the volumetric solidity of the coagulated blood mass is substantially equal. This is resulted due to the duration that particles with such a size can suspend in the whole blood they are mixed with. Larger particles tend to sink in the blood and the resulted coagulated blood mass is not homogeneous.
• the particle-size distribution D70 of the calcium gluconate powder is between 50g-200g.
• the calcium gluconate powder is first milled to a size of 2g.
• the particles product of this milling is typically undergoing a certain degree of granulation, thus prior to the use of the powder in the formation of the coagulated blood mass, the calcium gluconate powder is sifted through a sifter of 120-125g particles.
• Particle size of less than 120-125g dissolve much faster and therefore the use thereof in the formation of a coagulated blood mass results in a much more stable and non-leaky coagulated blood mass.
• particle-size distribution D90 of the calcium gluconate powder is between 50g-200g.
• the particle-size distribution D90, D80, D70, D60, or D50 of the calcium gluconate powder is about 125 pt.
• the term "about” should be understood as a deviation of up to 20% from the nominal value. For example, if the nominal value is about 125 g. then the value should be considered as 100g-150g.
• the particle-size distribution of either D50, D60, D70, D80, D90 or D95 of the calcium gluconate powder is between either 50g- 200g, 60g-190g, 70g-180g, 80g-170g, 90g-160g, 100g-150g, 110g-140g or 120g-130g.
• the particle-size distribution D99 of the kaolin powder is less than 50g.
• the particle-size distribution D99 of the kaolin powder is less than 50g.
• the kaolin particles suspend for a longer duration in the formed coagulating blood mass (when at least some of the blood is in liquid flowable form) and do not sink rapidly to the bottom of the formed coagulating blood mass, therefore resulting in a substantive homogeneous coagulated blood mass.
• the particle-size distribution D80 of the kaolin powder is less than 25g.
• the particle-size distribution D90 of the kaolin powder is less than 3g or between lg-3g. In some embodiments of the method, the particle-size distribution of either D50, D60, D70, D80, D90 or D95 of the calcium gluconate powder is less than either 30 pi, 25 pi, 20pi,15 pi, lOpt, 5p, 3p, 2p, Ip or less than O.lp.
• the method comprising withdrawing said whole blood from the subject, therefore the coagulated blood mass is prepared from autologous whole blood.
• the method comprising, prior to said mixing, introducing anti -coagulant-containing liquid to said amount of whole blood. Namely, after the whole blood is withdrawn, it is added with anti-coagulant to prevent undesired coagulation of the blood.
• said introducing comprises introducing between 0.04 ml - 0.095 ml of anti-coagulant-containing liquid for every 1 ml of whole blood.
• said introducing comprises introducing about 0.07 ml of anti-coagulant-containing liquid for every 1 ml of whole blood.
• said mixing is performed within a coagulation mold.
• the coagulation mold has a desired shape that determines the shape of the blood clot being prepared by the method.
• the mixing comprises mixing between 0.6 mg - 3.1 mg of kaolin powder with every 1 ml of whole blood.
• said mixing comprises mixing about 1.75 mg of kaolin powder with every 1 ml of whole blood.
• said mixing comprises mixing between 0.8 mg - 2.9 mg, 1 mg - 2.7 mg, 1.2 mg - 2.5 mg, 1.4 mg - 2.3 mg, 1.6 mg - 2.1 mg or 1.8 mg - 2 mg of kaolin powder with every 1 ml of whole blood.
• said mixing comprises mixing between 2.5 mg - 8.1 mg of calcium gluconate powder with every 1 ml of whole blood.
• said mixing comprises mixing about 5.3 mg of calcium gluconate powder with every 1 ml of whole blood.
• said mixing comprises mixing between 2.9 mg - 7.7 mg, 3.3 mg - 7.3 mg, 3.7 mg - 6.9 mg, 4.1 mg - 6.5 mg, 4.5 mg - 6.1 mg or 4.9 mg - 5.7 mg of calcium gluconate powder with every 1 ml of whole blood.
• a coagulation mold comprising a coagulation space defined by a base surrounded by upwardly rising walls and configured to receive a selected amount of whole blood.
• the coagulation space comprises calcium gluconate powder and kaolin powder.
• the coagulation mold comprises at least one of the following: (i) the particle-size distribution D50 of the calcium gluconate powder between 50p-200p, (ii) kaolin powder in an amount of between 0.6 mg - 3.1 mg for every 1 ml of said selected amount of whole blood, (iii) calcium gluconate in an amount of between 2.5 mg - 8.1 mg for every 1 ml of said selected amount of whole blood, or (iv) the particle-size distribution D50 of the kaolin powder is less than lOp.
• the particle-size distribution D70 of the calcium gluconate powder is between 50p-200p.
• the particle-size distribution D90 of the calcium gluconate powder is between 500p-200p.
• the particle-size distribution D90, D80, D70, D60, or D50 of the calcium gluconate powder is about 125 pi .
• the particle-size distribution of either D50, D60, D70, D80, D90 or D95 of the calcium gluconate powder is between either 50p-200p, 60p-190p, 70p-180p, 80p-170p, 90p-160p, 100p-150p, 110p-140p or 120p- 130p.
• the particle-size distribution D99 of the kaolin powder is less than 5 Op.
• the particle-size distribution D90 of the kaolin powder is less than 20p or less than lOp.
• the particle-size distribution D50 of the kaolin powder is less than 3p or between lp-3p.
• the particle-size distribution of either D50, D60, D70, D80, D90 or D95 of the calcium gluconate powder is less than either 30p, 25p, 20p,15p, lOp, 5p, 3p, 2p, Ip or less than O.lp.
• the whole blood being intended to be received therein comprises between 0.04 ml - 0.095 ml of anti-coagulant-containing liquid for every 1 ml of whole blood or in some embodiments about 0.07 ml of anti- coagulant-containing liquid for every 1 ml of whole blood.
• the coagulation mold comprising between 0.6 mg - 3.1 mg of kaolin powder for every 1 ml of said selected amount of whole blood.
• the coagulation mold comprising about 1.75 mg of kaolin powder for every 1 ml of said selected amount of whole blood.
• the coagulation mold comprising between 0.8 mg - 2.9 mg, 1 mg - 2.7 mg, 1.2 mg - 2.5 mg, 1.4 mg - 2.3 mg, 1.6 mg - 2.1 mg or 1.8 mg - 2 mg of kaolin powder with every 1 ml of whole blood.
• the mold comprising between 2.5 mg - 8.1 mg of calcium gluconate powder for every 1 ml of said selected amount of whole blood.
• the mold comprising about 5.3 mg of calcium gluconate powder for every 1 ml of said selected amount of whole blood.
• the coagulation mold comprising 2.9 mg - 7.7 mg, 3.3 mg - 7.3 mg, 3.7 mg - 6.9 mg, 4.1 mg - 6.5 mg, 4.5 mg - 6.1 mg or 4.9 mg - 5.7 mg of calcium gluconate powder with every 1 ml of whole blood.
• the volume of the coagulation space is sufficient to receive between 13 ml - 19 ml of whole blood.
• the volume of the coagulation space is sufficient to receive about 16 ml of whole blood.
• kits for preparing a coagulated blood mass comprising: calcium gluconate powder; kaolin powder; and a coagulation mold for mixing a selected amount of blood with the calcium gluconate powder and kaolin powder.
• the calcium gluconate powder and the kaolin powder are characterized by at least one of the following: (i) the particle-size distribution D50 of the calcium gluconate powder is between 50p.-200p, (ii) wherein said kaolin powder is an amount of between 0.6 mg - 3.1 mg for every 1 ml of said selected amount of whole blood, (iii) wherein said calcium gluconate is an amount of between 2.5 mg - 8.1 mg for every 1 ml of said selected amount of whole blood, or (iv) the particle-size distribution D50 of the kaolin powder is less than 10p.
• the kit comprising tools for withdrawing whole blood and containing it.
• the kit comprising 0.04 ml - 0.095 ml of anti-coagulant- containing liquid for every 1 ml of said selected amount of whole blood.
• the anti- coagulant-containing liquid can be contained separately in the kit or within the tool for containing the withdrawn whole blood.
• said selected amount is between 13 ml - 19 ml.
• the particle-size distribution D70 of the calcium gluconate powder is between 50g-200g.
• the particle-size distribution D90 of the calcium gluconate powder is between 50g-200g.
• the particle-size distribution D90, D80, D70, D60, or D50 of the calcium gluconate powder is about 125 pt.
• the particle-size distribution of either D50, D60, D70, D80, D90 or D95 of the calcium gluconate powder is between either 50 pi-200 pi, 60g- 190g, ZOpt-lSOpt, 80pi-170pi, 90pt-160pi, 100g-150g, 110g-140g or 120g-130g.
• the particle-size distribution D99 of the kaolin powder is less than 50g.
• the particle-size distribution D80 of the kaolin powder is less than login some embodiments of the kit, the particle-size distribution D50 of the kaolin powder is less than 3g or between lg-3g.
• the particle-size distribution of either D50, D60, D70, D80, D90 or D95 of the calcium gluconate powder is less than either 30g, 25g, 20g, 15g, 10g, 5g, 3g, 2g, 1g or less than 0.1g.
• the kit comprising between 0.6 mg - 3.1 mg of kaolin powder for every 1 ml of said selected amount of whole blood.
• the kit comprising about 1.75 mg of kaolin powder for every 1 ml of said selected amount of whole blood.
• the kit comprising between 0.8 mg - 2.9 mg, 1 mg - 2.7 mg, 1.2 mg - 2.5 mg, 1.4 mg - 2.3 mg, 1.6 mg - 2.1 mg or 1.8 mg - 2 mg of kaolin powder with every 1 ml of whole blood.
• the kit comprising between 2.5 mg - 8.1 mg of calcium gluconate powder for every 1 ml of said selected amount of whole blood.
• the kit comprising about 5.3 mg of calcium gluconate powder for every 1 ml of said selected amount of whole blood. In some embodiments, the kit comprising 2.9 mg - 7.7 mg, 3.3 mg - 7.3 mg, 3.7 mg - 6.9 mg, 4. 1 mg - 6.5 mg, 4.5 mg - 6.1 mg or 4.9 mg - 5.7 mg of calcium gluconate powder with every 1 ml of whole blood.
• the kit comprising the coagulation mold of any one of the above-described embodiments or any combination thereof.
• the kaolin powder and calcium gluconate powder are comprised within said coagulation mold.
• Figs. 1A-1B are images of the results of the kaolin powder particle size test.
• Fig. 1A shows the result in time zero and
• Fig. IB shows the result in time 15 minutes.
• Optimal clot is defined by:
• Visual clot structure strength - good structure strength is defined as the clot does not break down when extracted and handled by user
• Optimal clot is defined by:
• Coagulation time - good coagulation time is under 6 minutes
• Visual clot structure strength is defined as the clot does not break down when extracted and handled by user
• the goal of the test is to establish effective threshold of Kaolin powder to float in water for sufficient time to allow coagulation of blood simultaneously in all volume at the same time.
• Kaolin Blood coagulates rapidly via the extrinsic pathway when Kaolin or other coagulation initiator (such as glass) comes in contact with factor XI.
• Kaolin is a clay mineral that typically sink in water due to its weight. If Kaolin particles will be able to freely float in liquid it will have higher effect of coagulation, achieving an evenly distributed coagulation that starts at once in all the blood volume, similar in the upper part of the blood volume as in the lower part of the blood volume etc.
• the idea is that if kaolin particles are sufficiently small, they can float in the blood for a sufficient duration before they start to sink to allow homogenic coagulation initiation and acceleration, achieving a homogenic clot.
• Kaolin particle size lower that 25micron float in water and thus in blood for 15 minutes without sinking while kaolin particle larger than 25 micron will sink within timeframe of 15 minutes.

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• 2022
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