# US 9,517,255 B2 · Process, tube and device for the preparation of wound healant composition

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- Number: US 9,517,255 B2
- Document ID: US9517255B2
- Status: Granted
- Kind: B2
- Application number: 14/596,268
- Filed: 2015-01-14
- Published: 2015-05-07
- Granted: 2016-12-13
- Earliest claimed: 2010-03-11
- Applicants: Antoine Turzi
- Inventors: Antoine Turzi
- Web page: https://patentgrep.com/patent/US9517255B2

## CPC

- A61K 38/4833: {Thrombin (3.4.21.5)}
- A61K 8/981: {of mammals or bird}
- A61K 8/983: {Blood, e.g. plasma}
- A61K 31/728: Hyaluronic acid
- A61K 35/14: Blood; Artificial blood (perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42)
- A61K 35/15: Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00)
- A61K 35/16: Blood plasma; Blood serum (umbilical cord blood A61K35/51)
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 35/18: Erythrocytes (haemoglobin A61K38/42)
- A61K 35/19: Platelets; Megacaryocytes
- A61K 38/363: {Fibrinogen}
- A61L 26/0057: {Ingredients of undetermined constitution or reaction products thereof}
- A61L 26/0066: {Medicaments; Biocides}
- A61M 1/0209: {Multiple bag systems for separating or storing blood components}
- A61M 1/029: {Separating blood components present in distinct layers in a container, not otherwise provided for (containers for storing blood or blood components A61J1/05; sampling or analysing blood by separating blood components G01N33/491)}
- A61M 5/19: having more than one chamber
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/02: for peripheral neuropathies
- A61P 27/02: Ophthalmic agents
- A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- A61Q 19/08: Anti-ageing preparations
- C12Y 304/21005: Thrombin (3.4.21.5)
- A61L 2300/30: Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
- A61L 2300/412: Tissue-regenerating or healing or proliferative agents
- A61M 2202/0425: Thrombin
- A61M 2202/0427: Platelets; Thrombocytes
- 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)
- 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 (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- C12Y: ENZYMES

## Abstract

The present invention is related to the field of tissue regeneration. It concerns more particularly new processes, tubes and devices for thrombin, platelet concentrate and wound healant preparations, alone or in combination with cell extracts, cell compositions and uses thereof.

## Claims

### Claim 1

A composition comprising hyaluronic acid and at least one anticoagulant and at least one thixotropic gel, wherein said hyaluronic acid is layered beneath said thixotropic gel and/or wherein said thixotropic gel is layered beneath said anticoagulant.

### Claim 2 (depends on 1)

The composition according to claim 1, wherein said composition comprises hyaluronic acid, a thixotropic gel and an anticoagulant, wherein said hyaluronic acid is layered beneath said thixotropic gel and wherein said thixotropic gel is layered beneath said anticoagulant.

### Claim 3 (depends on 2)

A centrifugation tube comprising a composition according to claim 2.

### Claim 4 (depends on 3)

An article of manufacture comprising the centrifugation tube of claim 3.

### Claim 5 (depends on 3)

The centrifugation tube according to claim 3, wherein said centrifugation tube is:
a) a glass separator tube containing a polyester-based thixotropic gel, a buffered sodium citrate solution at 0.10 M and hyaluronic acid;
b) a polyethylene terephthalate separator tube containing a highly thixotropic gel formed by a polymer mixture, an anhydrous sodium citrate at 3.5 mg/m and hyaluronic acid,
c) a Cyclic Olefin Copolymer (COC) or Cyclic Olefin Polymer (COP) separator tube containing a polyester-based thixotropic gel, a buffered sodium citrate solution at 0.10 M and hyaluronic acid; or
d) a Cyclic Olefin Copolymer (COC) or Cyclic Olefin Polymer (COP) filter separator tube containing hyaluronic acid and a buffered sodium citrate solution at 0.10 M or an anhydrous sodium citrate at 3.5 mg/mL.

### Claim 6 (depends on 1)

The composition according to claim 1, wherein said composition further comprises:
a) enriched plasma and/or whole blood and/or bone marrow, and/or
b) a coagulation activator or thrombin serum, and/or
c) at least one cell extract, cell composition, tricalcium phosphate, bone substitute, chitosan, hyaluronic acid, cream, cream mask, fat cells, fat tissue, bone marrow concentrate, lubricin, cd-gelatin, botulinum toxin, calcium gluconate and/or stem cells,
wherein said cell extract is selected from an extract of: keratinocytes, bone marrow cells, osteoblasts, chondrocytes, fibroblasts, periosteum or corneal cells, melanocytes, Langerhans cells, fat cells, muscle cells, umbilical cord cells, mesenchymal stem cells (MSCs), preadipocytes, adipocytes, stem cells, periosteal cells, gingival cells, pre-endothelial cells, Schwann cells, ligament cells, tendon cells or pancreas islet cells.

### Claim 7 (depends on 6)

The composition according to claim 6, wherein the composition comprises:
a) plasma;
b) platelets at a concentration of at least 300×109 cells/L;
c) white blood cells at a concentration of at least 7×109 cells/L;
d) fibrinogen at a concentration of at least 3 mg/L;
e) optionally a coagulation activator or thrombin serum;
f) optionally at least one cell extract, cell composition, tricalcium phosphate (TCP), a bone substitute, chitosan, hyaluronic acid, cream, cream mask, fat cells, fat tissue, bone marrow concentrate, lubricin, cd-gelatin, botulinum toxin, calcium gluconate and/or stem cells,
wherein said cell extract is selected from an extract of: keratinocytes, bone marrow cells, osteoblasts, chondrocytes, fibroblasts, periosteum or corneal cells, melanocytes, Langerhans cells, fat cells, muscle cells, umbilical cord cells, mesenchymal stem cells (MSCs), preadipocytes, adipocytes, stem cells, periosteal cells, gingival cells, pre-endothelial cells, Schwann cells, ligament cells, tendon cells or pancreas islet cells.

### Claim 8 (depends on 7)

The composition according to claim 7, wherein the muscle cells are selected from myoblasts and satellite cells.

### Claim 9 (depends on 6)

The composition according to claim 6, wherein the thrombin serum, enriched plasma, cell composition, stem cells, fat cells, fat tissue, hone marrow concentrate and/or cell extract is autologous.

### Claim 10 (depends on 6)

A method of treating a subject comprising administering a composition according to claim 6 to a wound, damaged tissue, damaged bone, a periodontal defect or cavity or the skin of a subject.

### Claim 11 (depends on 6)

The composition according to claim 6, wherein the muscle cells are selected from myoblasts and satellite cells.

### Claim 12 (depends on 1)

The composition according to claim 1, wherein said anticoagulant is selected from anyhirudin, benzylsulfonyl-d-Arg-Pro-4-amidinobenzylamide (BAPA), heparin, sodium citrate, citrate, acid citrate dextrose (ACD), citrate-theophylline-adenosine-dipyridamole (CTAD), potassium-ethylenediaminetetraacetic acid (EDTA) or a combination thereof.

### Claim 13 (depends on 1)

A container comprising a composition according to claim 1.

### Claim 14 (depends on 13)

The container according to claim 13, wherein said container is a centrifugation tube.

### Claim 15 (depends on 14)

The centrifugation tube according to claim 14, wherein the centrifugation tube comprises the layer of hyaluronic acid, the layer of the thixotropic gel and the layer of anticoagulant, wherein the layers of hyaluronic acid, thixotropic gel and anticoagulant migrate across each other upon centrifugation of the centrifugation tube.

### Claim 16 (depends on 13)

The container according to claim 13, wherein said hyaluronic acid is at the bottom of said container and comprises about 1 ml to about 2 ml of hyaluronic acid.

### Claim 17 (depends on 13)

The container according to claim 13, comprising about 1 ml to about 2 ml of hyaluronic acid, about 2 g of thixotropic gel and about 1 ml of sodium citrate at 0.109M.

### Claim 18 (depends on 13)

The container according to claim 13, wherein said container:
i) has an inlet for introducing whole blood; and/or
ii) is held in a vacuum intended to aspirate a whole blood sample; and/or
iii) is sterile; and/or
iv) has a usable vacuum of or about 8 to about 10 mL; and/or
v) is suitable for undergoing centrifugation; and/or
vi) is sealed; and/or
vii) is manipulated entirely in closed circuit.

### Claim 19 (depends on 13)

An article of manufacture comprising the container of claim 13.

### Claim 20 (depends on 19)

The article of manufacture according to claim 19, wherein:
a) said article of manufacture is a medical device or kit;
b) said anticoagulant is sodium citrate; and
c) said container is a tube.

### Claim 21 (depends on 1)

An article of manufacture comprising a composition according to claim 1 within a container.

### Claim 22 (depends on 21)

The article of manufacture according to claim 21, wherein said anticoagulant is sodium citrate and said container is a tube wherein said container comprises hyaluronic acid at the bottom of said tube followed by said thixotropic gel which is followed by said anticoagulant.

### Claim 23 (depends on 21)

The article of manufacture according to claim 21, said composition within the container further comprising whole blood.

### Claim 24 (depends on 21)

The article of manufacture according to claim 21, said composition within the container comprising hyaluronic acid and enriched plasma.

### Claim 25 (depends on 21)

The article of manufacture according to claim 21, wherein:
a) said article of manufacture is a medical device or kit;
b) said anticoagulant is sodium citrate; and
c) said container is a tube.