EP1943349A2 - Plasma lyophilise riche en plaquettes destine a etre utilise dans la cicatrisation des plaies et dans les greffes osseuses ou tissulaires ou dans la reparation - Google Patents

Plasma lyophilise riche en plaquettes destine a etre utilise dans la cicatrisation des plaies et dans les greffes osseuses ou tissulaires ou dans la reparation

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Publication number
EP1943349A2
EP1943349A2 EP05793313A EP05793313A EP1943349A2 EP 1943349 A2 EP1943349 A2 EP 1943349A2 EP 05793313 A EP05793313 A EP 05793313A EP 05793313 A EP05793313 A EP 05793313A EP 1943349 A2 EP1943349 A2 EP 1943349A2
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EP
European Patent Office
Prior art keywords
platelets
wound healant
wound
plasma
thrombin
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP05793313A
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German (de)
English (en)
Inventor
James Bennie Gandy
Mackie J. Walker, Jr.
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Individual
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Individual
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Publication date
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Publication of EP1943349A2 publication Critical patent/EP1943349A2/fr
Withdrawn legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • 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
    • A61K35/16—Blood plasma; Blood serum
    • 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
    • A61K35/19—Platelets; Megacaryocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A61K38/4833—Thrombin (3.4.21.5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the invention relates to an improved Lyophilized platelet rich plasma used to make a platelet gel wound healant, and methods of preparation and use thereof for healing wounds are disclosed.
  • the improved wound healant comprises a therapeutically effective amount of activated growth factors with optional none, one or more additional anti-oxidant such as vitamin A and/or C and/or E, and/or one or more antibiotics and/or GHK-Cu (produced by
  • the present invention relates to improved Lyophilized platelet rich plasma for the use in wound healing and bone or tissue grafts and methods of making and use thereof of Lyophilized or fixed platelets.
  • the present invention generally relates to the therapeutic uses of blood platelets and fresh plasma that has been lyophilized, and more particularly to manipulations or modifications of platelets and plasma, such as in preparing freeze-dried compositions that can be rehydrated at the time of application and which when rehydrated have a normal response to thrombin and other agonists with respect to that of fresh platelets.
  • the inventive compositions are useful in applications such as wound care.
  • the platelets may be suspended, for example, in a solution containing a cryoprotectant at a temperature of about 22.degree. C. and then cooled to below 15. degree. C. This incorporates some cryoprotectant into the cells.
  • a wound is generally defined as an injury to an area of the body of a human or animal. Although injury to the surface of the skin is the most well known type of wound, the surfaces of internal organs may also be wounded, such as during surgery, rupture of the spleen or liver, or resulting from traumatic blows to the body surface in the vicinity of an internal organ.
  • Tissue wounds may have a wide spectrum of manifestations, as small as merely an abnormal microscopic tear or fissure in tissue (or a surface thereof), or as large as the abrasion or ablation of the skin covering a substantial portion of the body, such as in a burn victim.
  • Acute wounds covering a large or movable surface are usually the most difficult to guard from infection, and to heal.
  • Blood and bodily fluids include various substances that affect wound healing.
  • the blood is the primary medium for delivering healing agents to the wound site, and for transporting foreign or harmful substances away from the wound.
  • Whole blood is primarily comprised of three main types of cells suspended in a protein rich solution known as plasma.
  • the three main cell types in whole blood are erythrocytes (a.k.a. red blood cells), leukocytes (a.k.a. white blood cells) and thrombocytes (a.k.a. platelets).
  • the red blood cells are the iron-containing cells that facilitate the transport and transfer of oxygen to body tissue, and the removal of carbon dioxide.
  • the white blood cells perform a variety of functions such as phagocytosis of foreign bodies and production of antibodies, and are primarily responsible for fighting infection and foreign substances within the blood or wound site. Platelets perform many functions such as plugging leaks in blood vessels and helping begin the process leading to the formation of a blood clot; platelets contain substances known as growth factors that facilitate the formation of new tissue.
  • apheresis apheresis
  • the red and white blood cells and plasma may be separated out and returned to the donor's or patient's body, leaving the sequestered platelets in essentially concentrated form for use in wound healing techniques. This may be preformed at a blood collection center, blood bank, at the Physicians Clinic or Hospital. From blood extracted from a patient or from the other forms of collection methods, the platelets may thus be obtained and activated for use on the patient; methods of using a patient's own blood are called “autologous" or "autogenic" donor methods.
  • Another method using blood donated by one or more third parties for use by a patient are called “homologous” or “heterologous” donor methods, or collectively called “allogenic” methods.
  • One of the proteins suspended in plasma is fibrinogen, which reacts with substances released into (or attracted by) wound sites to produce sticky strands of fibrin. Such reactions result in the cross linking of the fibrin strands to form a mesh that holds and supports the deposit or growth of other tissue materials at the wound site. Therefore, the need for fresh plasma also known in the art "The Plasma Back Bone”.
  • the wound healing process is generally considered to occur in several stages, generally known as the healing cascade.
  • platelets are among the first cells to appear in the vicinity of the wound.
  • Activation of a platelet by an agonist such as thrombin, or other agonists such as those listed elsewhere herein leads to the release of granule material from within the platelet.
  • Such granulation activation results in the release of proteins known as growth factors, primarily concentrated in the alpha granules of platelets.
  • growth factors primarily concentrated in the alpha granules of platelets.
  • These released growth factors stimulate the formation of new tissue; when applied to wounds, growth factors have been known to increase the rate of collagen laydown, vascular ingrowth, fibroblast proliferation and overall healing.
  • PDGF platelet-derived growth factor
  • fibrin glue which often are essentially a mixture of co-coagulants (thrombin and calcium), concentrated fibrinogen and other coagulation proteins.
  • co-coagulants thrombin and calcium
  • fibrin glue the primary roles of fibrin glue are to seal wound surfaces to prevent loss of blood and other body fluids after surgery, and to provide adhesion between adjacent tissue surfaces. These products form a hard, cast-like covering over the area to be sealed, and tend to be non- yielding to limb movement. While there has been much research concerning fibrin glue, this material belongs to a separate field from the present invention, primarily because fibrin glues typically contain cryoprecipitated proteins without platelets. The use of fibrin glue is discussed extensively in the scientific literature; for example, see the references cited in U.S. Pat. No.
  • Wound treatment compositions derived from platelet enriched concentrates are known and possess certain advantages over materials without platelets such as fibrin glue.
  • One reason is that natural wound healing agents are released by the platelets.
  • the concentration of platelets likewise allows for a concentrated amount of wound healing factors.
  • Representative examples of platelet derived wound treatment compositions are described for instance in Hood U.S. Pat. No. 5,733,545; Knighton U.S. Pat. No. 5,165,938; and Gordiner U.S. Pat. No. 5,599,558.
  • This form of treatment has major problems, like time consuming and problems collecting blood sometimes with expensive machines and disposables.
  • Platelet concentrates are typically isolated by the process of differential centrifugation, which essentially allows separating the blood into at least three different components: packed erythrocytes (red blood cells), plasma and platelet concentrate.
  • Platelet concentrate can be combined with a solution of either sodium or calcium mixed with thrombin ("calcified thrombin"), which instantaneously form a composition of activated platelets that, when made with the necessary viscosity, can be utilized as a wound sealant.
  • thrombin thrombin
  • the chemical reactions and cascades that normally occur when thrombin is added to the concentrated platelets are indeed complex. See, for instance, Reeder, et al, in Proceedings of the American Academy of Cardiovascular Perfusion, Vol. 14, January 1993.
  • Such wound sealants typically set up into a hard mass covering the application site, thereby sealing the site against further blood loss and external contaminants.
  • an improved Lyophilized platelet enriched plasma wound treatment composition which avoids or diminishes the problems associated with typical platelet enriched wound compositions and would be desirable.
  • a dehydrated composition comprising freeze-dried platelets and fresh plasma that are effectively to preserve biological properties during freeze-drying and rehydration.
  • These platelets are rehydratable so as to have a normal response to at least one agonist, such as thrombin.
  • substantially all freeze-dried platelets of the invention when rehydrated and mixed with thrombin (1 U/ml) form a clot within three minutes at 37.degree. C.
  • the dehydrated composition can include one or more other agents, such as antibiotics, antifungals, growth factors, or the like, depending upon the desired therapeutic application.
  • the present invention relates to an improved Lyophilized platelet and plasma composition for wound treatment, a method of making and use thereof.
  • the composition comprises Lyophilized platelets and plasma composition in liquid form to the wound site and will gel to prevent the material from flowing away from the site.
  • Optional antibiotics may be included in the improved composition to prevent infections at the wound site.
  • Lyophilized platelet gels containing fresh plasma is prepared for topical application at the wound site and avoid the requirement for daily reapplication.
  • One such method is a process of preparing a dehydrated composition comprising providing a source of platelets and fresh plasma and lyophilizing the platelets and plasma. The rehydration preferably done with de- ionized water.
  • compositions of matter and the methods described herein are not limited solely to topical application.
  • the inventive composition increases the amount of growth factors in the wound, and thereby facilitates the promotion of the healing rate. This may be especially important in "wounded" patients, especially those with chronic wounds who may lack sufficient circulation to facilitate the healing cascade.
  • the invention described herein also facilitates the covering of the wound area with a substance that prevents or helps to reduce infection caused by most bacteria.
  • Practice of the invention permits the manipulation or modification of platelets and plasma while maintaining, or preserving, biological properties, such as a response to thrombin.
  • the inventive freeze-dried platelets and plasma including the freeze-dried platelets are substantially shelf stable at ambient temperatures when packaged in moisture barrier materials.
  • the invention described herein expands the uses for concentrated platelet materials, especially those in gel form, by improving the speed and convenience of making the composition; the invention described herein also improves the performance of the concentrated platelet composition, by making it more useable for applications over longer periods of time, and by enhancing the wound healing and infection fighting properties.
  • Another aspect of the present invention involves adding one or more antibiotic substance at one or more times during the processing period so that the resulting concentrated platelet and plasma composition contains either one or a variety of the antibiotics.
  • the use of an antibiotic in concentrated platelet and plasma compositions that enhances the complex healing cascade is indeed novel.
  • the invention disclosed herein involves adding such substances in a manner that does not detract from, substantially interfere with, or even destroy these different reactions, pH balances and potency.
  • Vitamins are known to have wound healing and anti-oxidant properties.
  • vitamins include vitamin E, vitamin A, vitamin C and other retinoids.
  • non-vitamin anti-oxidants may be included in the concentrated platelet gel.
  • Non-limiting representative examples of such anti-oxidants include beta-carotene.
  • the phrase blood collecting or blood extraction includes techniques, materials and apparatus known in the field, such as (for example) inclusion of anticoagulation materials, the use of blood drawing and infusion apparatus.
  • the phrase growth factor means any material(s) promoting growth of a tissue.
  • thrombin may include calcified thrombin, in particular, about 5,000 units of thrombin per 5 ml of 10% of aqueous calcium chloride solution; it may include calcified bovine thrombin as well as autologous thrombin, allogeneic thrombin or recombinant human thrombin.
  • viscosity means those characteristics of the specified material(s) determining the degree of gelation, such as (for example) the firmness or hardness of the material, or the degree to which the material resists flowing like a fluid.
  • therapeutically effective amount means the amount or amounts of the constituent elements or combination thereof necessary to enhance wound healing such as, for example, the reduction in the volume or surface area of a wound, the increase in the amount of granulation tissue or other biological material facilitating collagen laydown, vascular ingrowth, fibroblast proliferation or overall healing; all of the versions of the invention described herein are assumed to have the therapeutically effect amount(s) of constituent substances, or combinations thereof.
  • anti-oxidant refers to any material(s) having anti-oxidant properties.
  • Anti-oxidant would include, without limitation, vitamins such as vitamins C, A and E and non-vitamins such as -carotene.
  • the invention includes a wound healant composition comprising activated growth factors and ascorbic acid.
  • said growth factors are included within platelets.
  • the body produces many substances generally known as growth factors, and these growth factors are contemplated for use in the present invention.
  • the preferred growth factors for use in the present invention are selected from the group consisting of platelet-derived growth factor (PDGF), platelet-derived angiogenesis factor (PDAF), vascular endotheial growth factor (VEGF), platelet-derived epidermal growth factor (PDEGF), platelet factor 4 (PF-4), transforming growth factor .beta.
  • TGF-B acidic fibroblast growth factor
  • FGF-A basic fibroblast growth factor
  • FGF-B transforming growth factor .alpha.
  • TGF-A insulin-like growth factors 1 and 2
  • BCG thromboglobulin-related proteins
  • TSP thrombospondin
  • vWF von Wallinbrand's factor
  • fibropeptide A fibrinogen, albumin, plasminogen activator inhibitor 1 (PAI-1 ), osteonectin, regulated upon activation normal T cell expressed and presumably secreted (RANTES), gro-.alpha., vitronectin, fibrin D-dimer, factor V, antithrombin III, immunoglobulin-G (IgG), immunoglobulin-M (IgM), immunoglobulin-A (IgA), a2-macroglobulin, angiogenin, Fg-D, elastase, keratinocyte growth
  • each substance is known or believed to enhance cell or tissue growth.
  • said substances, or various combinations thereof are known or believed to function together in an unexpected synergistic manner to promote wound healing.
  • Suitable, non- limiting, anti-oxidants useful in the invention include but are not limited to vitamins such as vitamin C (ascorbic acid), vitamin E, vitamin A and other retinoids; and the carotenes such as beta-carotene. In practicing this invention, ascorbic acid as anti-oxidant is particularly preferred.
  • the platelets are separated from the red blood cells and white blood cells of whole blood, primarily through differential centrifugation, although any suitable method for separating platelets from whole blood may be employed in practicing this invention.
  • the overall composition of the invention disclosed herein may contain incidental amounts of white blood cells, due to the fact that the platelets are rarely totally isolated from the other blood components. It is believed that the present invention contains only minimal or trace amounts of white blood cells; it is believed that the white blood cell count of the present invention typically will be below about 3 times 10.sup.7 cell/ml.
  • the bioactive material in the invention is almost exclusively from platelets.
  • the range of the mean platelet volume of the platelets being sequestered is in the range of about 6.6 to 8.4 femtoliters, with an average of about 7.7 femtoliters; this may indicate that the platelets being sequestered are relatively larger or younger than the overall population of platelets.
  • Activation of growth factors may occur in a variety of manners, by a variety of substances known as activators or agonists.
  • said activation results from lysine and the inclusion of an activator or agonist selected from the group consisting of thrombin, glass, collagen, serotonin, adenosine diphosphate (ADP) and acetylcholine (ACH), and combinations thereof.
  • said growth factors are included within concentrated platelets, and said activation results from the inclusion of thrombin.
  • ADP adenosine diphosphate
  • ACH acetylcholine
  • the activator or agonist added to the platelet and plasma concentrate is in an amount sufficient to facilitate the formation of the coagulum (gel) having a predetermined viscosity while sufficiently activating growth factors present in the composition.
  • the amount of thrombin generally ranges between about 100 U and about 10,000 U, preferably about 900 LJ and about 1100 U, most preferably about 1000 U per 10 cc of platelet concentrate.
  • Thrombin is available as Thrombogen.RTM. thrombin, topical USP (bovine origin) in vials containing 5000 units thrombin (Johnson & Johnson Medical Inc., Arlington, Tex., USA).
  • the invention described herein may also include a method of treating a wound, comprising the steps of applying a sufficient amount of a composition of matter comprising growth factors to enhance healing of the wound.
  • Said method of treating a wound may include the use of any of the compositions described herein; it may also include the use of any composition made by any of the methods described herein.
  • the composition may remain on the wound for as long as 5 days, and perhaps longer depending upon the circumstances such as the location of the wound and other wound characteristics.
  • the composition and method described herein are especially useful for the treatment of chronic wounds, they may also be useful in the treatment of acute wounds.
  • Pooled or single donor platelets (containing at least 5 x 10 to the 9 th platelets) about 40ml to 50ml per bag.
  • Thaw the fresh frozen plasma ad insert an amount into the platelet plug container as to cause a platelet count of between 250,000 to 4,500,000 platelets per milliliter. Being very careful that the fresh plasma does not stay thawed for more than 4 hours. Gently rotate back and forth to cause the platelets and plasma to mix well. Pipette the desired amount of PRP into the vials to be lyophilized and place the stoppers in place.
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.
  • Thrombin (bovine) 1000u per milliliter Place on the wound and cover with a moist gauze. Cover the wound with an exclusive dressing. Allow too stay in place for 4 to 7 days without changing the dressing.
  • Pooled or single donor platelets (containing at least 5 x 10 to the 9 th platelets) about 40ml to 50ml per bag.
  • GHK-Cu ranging from .02mg/ml to .5mg/ml in liquid form Method: Remove the platelets from the bag and place in a 50ml tube and centrifuge for 15-20 min. at ⁇ OOOrpms to form a platelet plug, which is known in the art.
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.
  • 10ml of the PRP was Lyophilized and capped.
  • Pooled or single donor platelets (containing at least 5 x 10 to the 9 th platelets) about 40ml to 50ml per bag.
  • GHK-Cu ranging from .02mg/ml to .5mg/ml gauze Method:
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.
  • 10ml of the PRP was Lyophilized and capped.
  • 10ml vials of LPRP was Lyophilized and capped.
  • Pooled or single donor platelets (containing at least 5 x 10 to the 9 th platelets) about 40ml to 50ml per bag.
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.
  • 10ml of the PRP was Lyophilized and capped.
  • the Fifth Method for Human blood components obtained from a blood bank or collection center The components needed: Pooled or single donor platelets (containing at least 5 x 10 to the 9 th platelets) about 40ml to 50ml per bag.
  • Vitamin C is an amount equal to 10%
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.
  • 10ml of the PRP was Lyophilized and capped.
  • Vitamin C A.K.A. (Ascorbic Acid) Place on the wound and cover with a moist gauze. Cover the wound with an exclusive dressing. Allow too stay in place for 4 to 7 days without changing the dressing.
  • the sixth Method for Human blood components obtained from a blood bank or collection center The components needed: Pooled or single donor platelets (containing at least 5 x 10 to the 9 th platelets) about 40ml to 50ml per bag.
  • Centrifuge with the capabilities of spinning 50ml tubes up to 5000rpms.
  • Vitamin C is an amount equal to 10%
  • GHK-Cu ranging from .02mg/ml to .5mg/ml in liquid form
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.
  • Single donor platelets obtained from apheresis about 40ml to 50ml per bag. Centrifuge with the capabilities of spinning 50ml tubes up to 5000rpms. 50ml tubes. Pipettes from .01 ul to 50ml. Vials with stoppers and caps. Method:
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.
  • Pooled or single donor platelets (containing at least 5 x 10 to the 9 th platelets) about 40ml to 50ml per bag. Pooled or single donor fresh frozen plasma (about 250ml) per bag. Centrifuge with the capabilities of spinning 50ml tubes up to 5000rpms.
  • the first cycle should be for 48 hours.
  • the second cycle should be for 12 hours.

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Abstract

Cette invention porte sur un plasma amélioré, lyophilisé, riche en plaquettes, utilisé pour fabriquer un agent cicatrisant se présentant sous forme de gel plaquettaire, l'invention portant également sur des procédés de préparation et d'utilisation de ce plasma dans la cicatrisation des plaies. L'agent cicatrisant amélioré comprend des quantités effectives d'un point de vue thérapeutique de facteurs de croissance d'activation, d'un acide plaquettaire, de plasma (connu sous le nom de squelette de plasma), de globules blancs avec ou sans antioxydants additionnels tels que la vitamine A et/ou C et/ou E, et/ou avec ou sans antibiotiques et/ou GHK-Cu.
EP05793313A 2005-08-30 2005-08-30 Plasma lyophilise riche en plaquettes destine a etre utilise dans la cicatrisation des plaies et dans les greffes osseuses ou tissulaires ou dans la reparation Withdrawn EP1943349A2 (fr)

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PCT/US2005/031117 WO2007027178A2 (fr) 2005-08-30 2005-08-30 Plasma lyophilise riche en plaquettes destine a etre utilise dans la cicatrisation des plaies et dans les greffes osseuses ou tissulaires ou dans la reparation

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EP1943349A2 true EP1943349A2 (fr) 2008-07-16

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EP (1) EP1943349A2 (fr)
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US8449520B2 (en) 2007-03-19 2013-05-28 HemCon Medical Technologies Inc. Apparatus and methods for making, storing, and administering freeze-dried materials such as freeze-dried plasma
US20090223080A1 (en) * 2007-03-19 2009-09-10 Hemcon Medical Technologies, Inc. Apparatus and methods for making, storing, and administering freeze-dried materials such as freeze-dried plasma
WO2011124280A1 (fr) * 2010-04-08 2011-10-13 INSERM (Institut National de la Santé et de la Recherche Médicale) Procédé de zéodratation utilisé pour la conservation des plaquettes sanguines
WO2015071364A1 (fr) * 2013-11-14 2015-05-21 Nte-Sener, S.A. Procédé pour obtenir une composition riche en cytokine et composition obtenue au moyen de ce procédé

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US5378461A (en) * 1991-07-12 1995-01-03 Neigut; Stanley J. Composition for the topical treatment of skin damage
AU4648697A (en) * 1996-09-23 1998-04-14 Chandrashekar Pathak Methods and devices for preparing protein concentrates
WO2001058266A1 (fr) * 2000-02-10 2001-08-16 The Regents Of The University Of California Plaquettes et procedes therapeutiques

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CA2621140A1 (fr) 2007-03-08

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