US20050142208A1 - Pharmceutical composition for treatment of wounds conntaining blood plasma or serum - Google Patents

Pharmceutical composition for treatment of wounds conntaining blood plasma or serum Download PDF

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US20050142208A1
US20050142208A1 US10/508,841 US50884104A US2005142208A1 US 20050142208 A1 US20050142208 A1 US 20050142208A1 US 50884104 A US50884104 A US 50884104A US 2005142208 A1 US2005142208 A1 US 2005142208A1
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wounds
pharmaceutical composition
composition according
wound
treatment
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Won Min Yoo
Kyung Chang
Nae Yoo
Ki Keum
Sang Lee
Gene Lee
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Healagenics Inc
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MEDIGENES
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Priority to PCT/KR2003/000922 priority patent/WO2003094937A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • A61K35/16Blood plasma; Blood serum

Abstract

The present invention relates to a pharmaceutical composition for the treatment of wounds containing blood plasma or serum and a method for treating wounds effectively by applying said composition to the wound site to normalize the tissue-environment around the site.

Description

    TECHNICAL FIELD
  • The present invention relates to the use of blood plasma or serum as an agent for the treatment of wounds. More specifically, the present invention relates to a pharmaceutical composition for the treatment of wounds comprising blood plasma or serum and a method for treating wounds effectively by applying said composition to a wound site to normalize the tissue-environment around the wound site.
  • BACKGROUND ART
  • The early studies on the treatment of wounds have laid emphasis on a close examination of the functions of the cell stage, i.e., the functions of inflammatory cell and platelet [Allgower M. and Hulliger L., Surgery, 47, 603 (1960); Dicoreto P. E. and Browen-Pope D. F., Proc. Natl. Acad. Sci. USA, 80, 1919 (1983); and Houck J. C. et al., Biochem. Pharmacol., 17, 2081 (1968)].
  • Recently, growth factors to promote tissue growth have been used in the treatment of wounds such as chronic ulcers. The growth factors stimulate mitogenesis, which is the proliferation of cells such as fibroblast. The growth factors also stimulate angiogenesis, resulting in the ingrowth of new blood vessels. Moreover, the synthesis of collagen and extracellular matrix proteins is stimulated by the growth factors (L. Greenhalgh, J. Trauma 41: 159 (1996)).
  • Cytokines have been found as growth factors associated with wound healing. Representative examples of such cytokines include basic fibrogrowth factor which is produced by keratinocytes and fibroblasts and promotes the growth of epithelial cells; platelet-derived growth factor(PDGF) which is produced by platelets and the endothelium and other cell types and promotes the abnormal proliferation of epithelial cells in association with epidermal growth factor(EGF); transforming growth factor-β(TGF-β) which is produced by fibroblasts and platelets and promotes the growth of connective tissue; epithelial cell-growth factor which is generated in salivary glands-stimulatory glands and promotes the proliferation of epithelial cells; fibroblast growth factor(FGF); and interleukin-1 which is produced by macrophages and epithelial cells and promotes the growth and mobility of epithelial cells. Becaplermin is a genetically engineered recombinant PDGF that is commercially available as an agent for the treatment of wounds in topical formulations by Johnson & Johnson under the trade name of Regranex®. EP 0 575 484 B1 discloses a pharmaceutical composition for the regeneration and repair of mammalian tissues which includes PDGF and dexamethasone. U.S. Pat. No. 5,981,606 discloses a pharmaceutical composition for treating wounds which includes TGF-β. WO 96/30038 discloses a pharmaceutical composition for wound healing which includes TGF-β and fibric acid together with antioxidants. U.S. Pat. No. 5,183,805 discloses a pharmaceutical composition having the effect of the regeneration of tissues which includes EGF. Japanese Patent No. 05070365 and U.S. Pat. No. 6,165,978 disclose wound healing formulation containing FGF.
  • Formulations utilizing hyaluronic acid as an active agent have also been reported as being useful in the treatment of skin ulcers (See U.S. Pat. No. 5,897,880). Formulations including sodium hyaluronate are marketed by LAM Pharmaceutical Corporation under the trade name of IPN Wound Gel®.
  • Topically applied fibronectin (glycoprotein found in blood plasma) has also been reported as being useful for increasing the rate of wound healing in corneal wounds (Nishida, Larch Opthalmology 101: 1046 (1983)) and leg ulcers (Wysocki et al., Arch. Dermatol. 124: 175 (1988)).
  • Although such treatments provide some patients with partial wound relief, they need long healing time and fail to exhibit optimum response to the treatment. As wounds, especially, chronic skin ulcers, become serious clinical problems, much effort has been made in finding effective treatments of the wounds. The underlying causes responsible for poor wound closure are complex and still poorly understood.
  • Therefore, it would be desirable to develop new and improved methods of treating wounds. Use of the present formulations either alone or in combination with various known therapeutic agents overcomes the limitations of the prior art.
  • SUMMARY OF THE INVENTION
  • The inventors of the present invention have surprisingly found that blood plasma or serum is highly effective in the treatment of wounds. We found that partial defect wounds could be healed in several days after application of the formulation containing blood plasma or serum according to the present invention. We more surprisingly found that large full defect wounds could be healed within several weeks (about 2 to 6 weeks) after application of the formulation containing blood plasma or serum according to the present invention. These findings represent very significant improvements in both response to treatment and healing time over conventional treatments or other therapeutics currently available or reported until now.
  • In one aspect, the present invention provides a pharmaceutical composition for wound healing which comprises a pharmaceutically effective amount of blood plasma or serum in combination with a pharmaceutically acceptable carrier.
  • In another aspect, the present invention provides a method of treating wounds of a subject which comprises applying a pharmaceutical composition comprising a pharmaceutically effective amount of blood plasma or serum to the wound of the subject in need of such treatment.
  • BRIEF DESCRITION OF THE DRAWINGS
  • FIG. 1A is a photograph of the wound tissue of the control rat group on day 7 after it was treated with distilled water (trichrome-stained and viewed with 100× magnification).
  • FIG. 1B is a photograph of the wound tissue of the test rat group on day 7 after it was treated with the liquid human blood plasma according to the present invention (trichrome-stained and viewed with 100× magnification).
  • FIG. 2A is a photograph of the wound tissue of the control rat group on day 7 without any treatment after it was wounded (trichrome-stained and viewed with 100× magnification).
  • FIG. 2B is a photograph of the wound tissue of the test rat group on day 7 after it was treated with the powdered human blood plasma according to the present invention (trichrome-stained and viewed with 100× magnification).
  • FIG. 3A is a photograph of the wound tissue of the control rat group on day 7 after it was treated with a water-soluble ointment base alone (trichrome-stained and viewed with 100× magnification).
  • FIG. 3B is a photograph of the wound tissue of the test rat group on day 7 after it was treated with the ointment containing human blood plasma according to the present invention (trichrome-stained and viewed with 100× magnification).
  • FIG. 4A is a photograph of the wound tissue of the control rat group on day 7 without any treatment after it was wounded (trichrome-stained and viewed with 100× magnification).
  • FIG. 4B is a photograph of the wound tissue of the test rat group on day 7 after it was treated with the powdered fetal bovine serum (FBS) according to the present invention (trichrome-stained and viewed with 200× magnification).
  • FIG. 5A is a photograph of the wound tissue of the control rat group on 7 day after it was treated with a water-soluble ointment base alone (trichrome-stained and viewed with 100× magnification).
  • FIG. 5B is a photograph of the wound tissue of the test rat group on day 7 after it was treated with the ointment containing FBS according to the present invention (trichrome-stained and viewed with 100× magnification).
  • FIG. 6A is a photograph of the wound tissue of the control rat group on day 7 after it was treated with PDGF ointment (Regranex® 0.01%) (trichrome-stained and viewed with 200× magnification).
  • FIG. 6B is a photograph of the wound tissue of the test rat group on day 7 after it was treated with the ointment containing FBS according to the present invention (trichrome-stained and viewed with 200× magnification).
  • FIG. 7 is a photograph of rat abdomen with full thickness defect wounds on day 4 and day 7 after it was treated with the PDGF ointment and the ointment containing human blood plasma according to the present invention.
  • FIG. 8 is a photograph of a second degree burn on day 1, day 2 and day 4 after it was treated with the ointment containing FBS according to the present invention.
  • FIG. 9 shows a protocol for treatment of chronic wounds according to one or more embodiments of the present invention.
  • DETAILED DESCRIPTION OF THE INVENTION
  • The present invention generally relates to the use of blood plasma or serum which is useful for treating wounds. The blood plasma or serum used as an active agent in a pharmaceutical composition according to the present invention is highly effective in the treatment of wounds.
  • Wounds are damaged conditions of living bodies and encompasses cut or disrupted pathological conditions of tissues constituting the internal and external surface of the living body, for example skin, muscle, nervous tissue, bone, soft tissue, inner organs and vascular tissue. The exemplary wounds include, but are not limited to, contusion or bruise, non-healing traumatic wounds, tissue disruption by irradiation, abrasion, gangrene, laceration, avulsion, penetrated wound, gun shot wound, cutting, burn, frostbite, cutaneous ulcers, xeroderma, skin keratosis, breakage, rupture, dermatitis, dermatophytosis, surgical wounds, wounds caused by vascular disorders, corneal wounds, sores such as pressure sore and bed sore, diabetes and poor circulation-associated conditions diabetic skin erosion, chronic ulcers, suture site following plastic surgery, spinal traumatic wounds, gynecological wounds, chemical wounds and acne. Any damaged or injured part of the living body is within the definition of the wounds. In this respect, the composition comprising blood plasma or serum according to the present invention can be useful for the repair, replacement, alleviation, acceleration, promotion, healing and/or curing of any damaged or injured tissue.
  • Blood plasma used as an active ingredient in the composition of the present invention typically indicates the straw-colored liquid portion remaining after the material bodies such as blood cells and cell fragments were separated out from the blood. The components of the plasma are well known in the art (Philip Westerman, Plasma Proteins, VII-1 to VIII-13, Sep. 17, 2002; and Wendy Y. Craig, et al., Plasma Proteins Pocket Guide, Foundation for Blood Research—each of which is incorporated by reference in its entirety). Serum is also well defined and generally called as blood plasma without fibrinogen and other clotting factors.
  • The source of blood plasma or serum used in the composition of the present invention includes humans and mammalian species, for example, primates, rodents and livestock such as sheep, goat, pig, horse, dog and cattle.
  • The blood plasma or serum used in the present invention can be readily obtained from the blood using conventional methods such as centrifugation, sedimentation and filtration. Centrifugation would be carried out under any conditions suitable to sediment blood cells and cell fragments, e.g., about 3,000 rpm for about 10 minutes. This condition is sufficient to remove substantially all cell fragments (platelets) as well as red and white blood cells.
  • The supernatant plasma can be easily separated from the centrifuged cells by standard techniques. Such separation can be achieved using filtration by passing the supernatant plasma through a suitable filter. The filters include a microporous membrane through which proteins are well penetrated.
  • Blood plasma or serum can be fresh liquid plasma or liquid preparation obtained by centrifugation or sedimentation of whole blood. In addition, blood plasma or serum are known to be reserved in various forms prior to use, including fresh-frozen preparation, cryoprecipitated preparation, lyophilized preparation or concentrated preparation. Such all forms of plasma or serum can be used for the present invention. The fresh-frozen plasma is obtained by centrifuging the blood at about 2,800 rpm for 15 minutes to separate out blood cells and cell fragments and freezing the remaining liquid portion at the temperature of from about −18° C. to −40° C. The centrifugation is carried out within six hours from blood collection. For the use, fresh-frozen plasma is thawed out in warm water at the temperature of from about 30° C. to 37° C.
  • The cryoprecipitated plasma is obtained by thawing out one unit of a fresh-frozen plasma at the temperature of 4° C. to form white precipitate (cold precipitated protein) (including large amounts of factors such as VIII:C, fibrinogen, XIII and fibronectin), isolating the formed precipitate and refreezing it at the temperature of from about −18° C. to −40° C. For its use, the cryoprecipitated preparation is thawed out by putting in a refrigerator at the temperature of from 1° C. to 6° C. overnight. It may be put in a water bath at the temperature of about 4° C. to melt down more rapidly. The concentrated plasma is obtained by separating plasma from whole blood, concentrating the separated plasma by mixing it with a thickener such as dextranomer, SEPHADEX, dextramine, polyacrylamide, BIO-GEL P, silica gel, zeolite, DEBRISAN, crosslinked agarose, starch and alginate gel and discarding the remaining thickener.
  • In one embodiment of the present invention, the blood plasma or serum used for the present invention can be those commercially available, for example, powdered preparations purchased from blood banks. These preparations are derived from units of human blood plasma, which have been tested to elicit no antigen-antibody reaction, for example, non-reactive for antibodies to hepatitis B surface antigen (HBsAg) and hepatitis C (HCV) antibody and negative for antibodies HIV-1 and HIV-2 viruses. All units of blood plasma or serum used to prepare such preparations are certified free of pathogens.
  • To reduce the potential risk of transmission of infectious agents, the preparation may be treated with an organic solvent/detergent mixture, for example, tri(n-butyl)/phosphate/polysorbate 80 designed to inactivate enveloped viruses such as HIV, hepatitis B and HCV. The inactivation and removal of viruses can be enhanced by additionally performing a nanofiltration step.
  • In another embodiment, the plasma or serum preparation can be prepared through purification, i.e., using solvent detergent and nanofiltration, or pasteurization of a liquid plasma fraction. Alternatively, the whole blood may be purified. The resultant plasma or serum fraction can be powdered by heating, lyophilization or other suitable drying techniques. By way of example only, blood plasma is freeze-dried at the temperature of less than −40? for several days (e.g., about 7 days). Any conventional techniques and parameters known to those of skill in the art may be used.
  • In another further embodiment of the present invention, the blood plasma or serum may be in the form of sheet in addition to powder. The sheet is produced by putting the plasma or serum into an appropriate template and dehydrating it. In a still another further embodiment, the sheet can be provided with mechanical strength and/or physical integrity by incorporating a thickening agent or carrier into the blood plasma or serum fraction.
  • In a preferred embodiment of the present invention, blood plasma or serum is adjusted to acidic pH. We found that the acidified blood or serum has a superior wounds healing efficacy to weakly alkaline plasma or serum. Preferably, the plasma or serum has acidic pH values of from about 3.5 to 6.5. The blood plasma or serum can be acidified using pharmaceutically acceptable inorganic or organic acids. The examples of the pharmaceutically acceptable inorganic acid include, but are not limited to, hydrochloric acid, nitric acid, sulfuric acid and phosphoric acid. The examples of the pharmaceutically acceptable organic acids include, but are not limited to, formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, benzenesulfonic acid and p-toluenesulfonic acid.
  • According to the present invention, the blood plasma or serum in the form of liquid or powder can be applied directly onto the wound, i.e., sprinkled over the wound site. The plasma in the form of sheet may be applied over the wound site, which is then dressed suitably to protect the wound and prevent the healing effects of the active ingredient from diminishing. Any commercially available or conventional wound dressing may be used in the present invention. The examples of commercially available wound dressings include, but are not limited to, Compeel, Duoderm, Tagaderm and Opsite.
  • The composition containing a pharmaceutically effective amount of blood plasma or serum in combination with a pharmaceutically acceptable carrier can be formulated into a variety of forms by means known in the pharmaceutical art. The administration forms include, but are not limited to, conventional dosage forms of external preparation, e.g., liquid paints, sprays, lotions, creams, gels, pastes, liniments, ointments, aerosols, powders and transdermal absorbers. Actual methods for preparing administrable compositions will be known or apparent to those skilled in the art and are described in more detail in such publications as Remington's Pharmaceutical Science, 15th Edition, 1975, Mack Publishing Company, Easton, Pa. 18042 (Chapter 87: Blaug, Seymour), the contents of which are incorporated herein by reference.
  • In the external preparation of the present invention, suitable carriers can be chosen depending on the dosage forms and include, but are not limited to, hydrocarbons such as vaseline, liquid paraffin, and plasticized hydrocarbon gel(plastibase); animal and vegetable oils such as medium-chain fatty acid triglyceride, lard, hard fat, and cacao oil; higher fatty acid and alcohols and esters thereof such as stearic acid, cetanol, stearyl alcohol, and palmitic acid isopropyl; water-soluble bases such as Macrogol(polyethylene glycol), 1,3-butylene glycol, glycerol, gelatine, white sugar, and sugar alcohol; emulsifiers such as glycerine fatty acid ester, stearic acid polyoxyl, and polyoxyethylene/or curing castor oils; thickeners such as acrylic acid esters, and sodium alginates; propellants such as liquefied petroleum gas, and carbon dioxide; and preservatives such as paraoxybenzoic acid esters. The external preparation of the present invention can be prepared with the aforementioned carriers by methods well-known to those skilled in the art. In addition to said carriers, additives such as stabilizers, pigments, coloring agents, pH adjusting agents, diluents, surfactants, and antioxidants are, if necessary, used. The external preparation of the present invention can be applied to the tropical wound site by conventional methods.
  • The external preparation according to the present invention may be also used in adhesion onto a solid support such as a wound covering release layer. The adhesion is achieved by saturation of the solid support with the blood plasma or serum fraction, followed by dehydration of the fraction. In one embodiment of the present invention, the solid support is first coated with an adhesion layer to improve the adhesion of the blood plasma or serum to the solid support. Exemplary adhesion materials include polyacrylate and cyanoacrylate. As such formulation, there is provided a number of commercially available products, including bandage having non-adhesive wound-covering release layer in a perforated plastic film by Smith & Nephew Ltd., BAND-AID in thin strip, patch, spot and thermoplastic strip forms by Johnson & Johnson, CURITY and CURAD (“ouchless” type of bandage) by Kendall Co. (a division of Colgate-Palmolive Company), and STIK-TITE (elastic strip) by American White Cross Labs, Inc.
  • In one embodiment, the pharmaceutical composition according to the present invention can be formulated into a liquid paint preparation by mixing powdered plasma or serum with physiologic saline at a fixed ratio by volume and adjusting the pH value of the resulting mixture to the range of from 3.5 to 6.5. In another embodiment, the pharmaceutical composition according to the present invention can be formulated into an ointment preparation by mixing the powdered plasma or serum with a water-soluble ointment base and adding physiologic saline to the resulting mixture. Preferably, the pH value of the ointment is adjusted to the range of from 3.5 to 6.5.
  • According to the present invention, pharmaceutical carriers such as gels or microspheres may be used to promote the wound healing. A variety of microsheres of a polymer as carriers for one or more pharmaceutically or cosmetically active substances is described in U.S. Pat. No. 5,264,207, WO 2000/24378, WO96/13164 and WO 94/13333, the entire contents of which are incorporated herein by reference.
  • The pharmaceutical composition of the present invention can be used to treat a variety of wounds in mammalian animals. Especially, the composition of the present invention is effective for the treatment of non-healing ulcers, including those due to infection, malignancy, large vessel arterial insufficiency, small vessel arterial insufficiency, deep venous blockage or insufficiency, superficial venous insufficiency(varicose veins), lymphatic obstruction, intrinsic circulatory insufficiency, hematologic abnormalities, collagen vascular disorders, radiation dermatitis, trophic causes and the like.
  • A particular condition that can be treated with the pharmaceutical composition of the present invention includes radiation ulcers. Radiotherapy (for example, in the treatment of cancer) often leads to non-healing skin ulcers. Such ulcers do not respond well to conventional therapies as a result of poor circulation in the radiated tissue and are often treated with low intensity laser irradiation. Radiation ulcers respond well to treatment with the composition comprising the blood plasma or serum according to the present invention. In one embodiment of the present invention, 1 gm dose of the composition containing 5% by weight of blood plasma or serum is applied to a 5 cm2 surface area having a thickness of from about 1.5 to 2 mils.
  • The pharmaceutically effective amount of the blood plasma or serum contained in the composition of the present invention refers to an amount which normalizes various cell-activating substances and abnormal cells around the wound site and promotes the wound healing. As one of skill in the art will appreciate, the amount may vary depending on the wound type being treated, the wound site to be treated, the frequency and time of administration, the route and form of administration, the severity of the wound being treated, the kinds of vehicles, and other factors.
  • Generally, 2 to 5% by weight of powdered blood plasma or serum are administered per dose. The frequency of administration may range between twice daily and once per week. In a specific embodiment, full thickness defect wounds are treated with from 0.01 to 0.1 g/cm2 of the pharmaceutical composition of the present invention daily, preferably from 0.02 to 0.09 g/cm2, more preferably from 0.02 to 0.07 g/cm2.
  • An exemplary protocol 100 for the treatment of chronic non-healing wound is shown in FIG. 9. A defect wound is evaluated for determination of suitability for treatment with the active ingredient of the present invention, as shown in step 110 of FIG. 9. The treatment is appropriate for full thickness defect wounds such as diabetic ulcers, radiation ulcers, pressure sore, third degree burns and other tissue necrosis. The treatment is also appropriate for partial thickness defect wounds such as second degree burns, radiation dermatitis and tissue damaged during dermabrasion.
  • Once a defect wound is identified as suitable for the treatment according to the invention, the wound is cultured (step 120) to determine whether infection is present. The wound tissue is debrided, if needed. Stage 4 ulcers require debridement; some ulcers may also require deeper surgery. When the ulcers are filled with pus and necrotic debris, application of dextranomer beads or other hydrophilic polymers may hasten the tissue debridement without surgery. Conservative debridement of necrotic tissue with forceps and scissors should be instituted. Some debridement may be done by cleansing the wound with 1.5% hydrogen peroxide. Wet dressings of water (especially whirlpool baths) will assist in debriding. The granulation that follows removal of necrotic tissue may be satisfactory for skin grafts to cover small areas.
  • When the culture is positive, the wound is treated for the infection (step 140). Wet dressing including an antibiotic (step 145) may be applied prior to blood plasma or serum treatment, or a formulation including powdered plasma or serum in combination with antibiotic is applied (step 148). Exemplary antibiotics include, but are not limited to, penicillinase-resistant penicillin or cephalosporin.
  • Where the culture is negative (step 150), no antibiotics need to be applied, and the wound is treated with the powdered plasma or serum of the invention (step 155).
  • The powdered plasma or serum is applied to the wound in any of a variety of formulations disclosed herein, and the wound is dressed with conventional wound dressings, such as Compeel, Duoderm, Tagaderm or Opsite wound dressings. Depending on the amount of blood plasma or serum to be administered and the desired release profile of the blood plasma or serum from the pharmaceutical carrier, dressings are changed at intervals ranged between 1 day and 5 days, and may be changed at intervals of 3-4 days. Depending on the extent of damage to the underlying tissue, healing of partial thickness defect wounds is observed in as little as 4 days and of full thickness defect wounds in as little as 2-4 weeks.
  • The present invention will be more specifically illustrated by the following examples. The following examples are provided to illustrate the present invention, but are not intended to be limited.
  • EXAMPLES Example 1
  • Preparation of Blood Plasma in Liquid Phase
  • A human fresh-frozen blood plasma preparation (Central Blood Center of The Republic of Korea National Red Cross, Seoul, Korea), which was certified negative for pathogens including HIV, HCV and hepatitis B, was thawed out at the temperature of 30° C. and then mixed with physiologic saline at the ratio by volume of 10:1. The pH of the resulting mixture was adjusted to the value of 5.5 by adding 1N HCl or 1N NaOH with stirring to afford the desired liquid plasma. The pH value was measured using the Orion pH Meter.
  • The remaining blood plasma preparation was cryopreserved in lyophilization bottles, vials, containers or trays, or in other storage bottles.
  • Example 2
  • Preparation of Lyophilized Blood Plasma in Powder Form
  • A human fresh-frozen blood plasma preparation (Central Blood Center of The Republic of Korea National Red Cross, Seoul, Korea), which was certified negative for pathogens including HIV, HCV and hepatitis B, was thawed out at the temperature of 30?. 500 ml of the resulting liquid blood plasma was placed into a lyophilization bottle and then frozen at the temperature of −80° C. (Deep Freezer, Form a Science, Inc., Ohio, USA) for 8 hours. The frozen bottle was mounted on a freeze drying/lyophilization system (Labconco Corporation, Kansas City, Mo., USA) and lyophilized at the temperature of −48° C. for 7 days. All processes were under sterile conditions. 500 ml of liquid blood plasma provides approximately 30 g of lyophilized plasma powder.
  • Example 3
  • Preparation of Ointment Formulation
  • 5 g of plasma powder prepared as described in Example 2 was mixed with 95 g of water-soluble ointment base (SAM-A base, SAM-A Pharmaceutical Ind. Co., Ltd., Seoul, Korea).
  • A proper quantity of physiologic saline was added to the resulting mixture with stirring to afford the desired ointment. The ointment base consists of 38 mg of sperm wax, 116 mg of stearyl alcohol, 38 mg of polyethylene glycol 4000, 192 mg of concentrated glycerine, 23 mg of cetanol, proper quantity of purified water, 9 mg of sodium lauryl sulfate, 0.87 mg of paraoxybenzoic acid ethyl and 0.12 mg of paraoxybenzoic acid butyl, based on 1 g of the base.
  • Example 4
  • Preparation of pH-Adjusted Ointment
  • 5 g of plasma powder prepared as described in Example 2 was mixed with 95 g of a water-soluble ointment base (SAM-A base, SAM-A Pharmaceutical Ind. Co., Ltd., Seoul, Korea). A proper quantity of physiologic saline was added to the resulting mixture to produce an ointment. 1N HCl or 1N NaOH was added to the ointment with stirring to afford the ointment having the pH value of 5.5, which was determined using the Orion pH Meter.
  • Example 5
  • Preparation of Lyophilized Blood Plasma in Powder Form
  • 500 ml of fetal bovine serum (FBS, Biofluids, Inc., Rockville, Md., USA) having not greater than 0.1 ng/mg of endotoxin capacity and not greater than 30 ng/100 ml of hemoglobin capacity was placed into a lyophilization bottle and then frozen at the temperature of −80° C. (Deep Freezer, Form a Science, Inc., Ohio, USA) for 6 hours. The frozen bottle was mounted on a freeze drying/lyophilization system (Labconco Corporation, Kansas City, Mo., USA) and lyophilized at the temperature of −48° C. for 7 days to afford the desired lyophilized plasma powder. All processes were under sterile conditions.
  • Example 6
  • Preparation of Ointment
  • 5 g of plasma powder prepared as described in Example 5 was mixed with 95 g of a water-soluble ointment base (SAM-A Pharmaceutical Ind. Co., Ltd., Seoul, Korea). A proper quantity of physiologic saline was added to the resulting mixture to produce an ointment. 1N HCl or 1N NaOH was added to the ointment with stirring to afford the desired ointment having a pH 5.5, which was determined using the Orion pH Meter.
  • Example 7
  • Preparation of Gel
  • 5 parts by weight of plasma powder prepared as described in Example 2 was mixed with 95 parts by weight of an emulsion, which consists of 38 mg of Carbopol ETD 2020, 116 mg of glycerin, 38 mg of propylene glycol, 192 mg of triethanolamine and a proper quantity of purified water, to afford a clear gel with pHs 5.8-6.0. Carbopol ETD 2020 is the mixture of acrylates and C10-30 alkyl acrylate crosspolymer.
  • Experimental Example 1
  • Wound-Healing Effect of Human Liquid Blood Plasma
  • The human liquid blood plasma according to the present invention as prepared in Example 1 was applied to a full thickness defect wound to histologically study whether it promotes the formation of granulation tissue on the wound. Ten adult white Sprague-Dawley rats weighing 300-350 mg were used in this experiment.
  • The animal abdomen was completely shaved and subjected to full thickness defect wound with the size of 10 mm×10 mm. Two wounds were created near both upper limbs, respectively. Likewise, two wounds were created near both lower limbs, respectively. Over each of the two wounds on left side upper and lower limbs, two layers of gauze with the size of 10 mm×10 mm wetted by 0.3 ml of liquid blood plasma having a pH 5.5 was applied. As control, over each of the two wounds on right side upper and lower limbs, two layers of gauze with the size of 10 mm×10 mm wetted by 0.3 mol of distilled water was applied. Then a dressing film (Tagaderm, 3M) was placed over that, which was sewed up on all four sides by 5/0 nylon suture so as not to be detached over the experimental period.
  • On day 7 after the experiment, wound tissues were taken. Biopsies were 10% neutral buffered formalin fixed for 24 hours and paraffin embedded. The paraffin-embedded biopsies were dissected 4 um in thickness. Sections were stained with hematoxyline-eosine and Masson's trichrome for the visualization of connective tissues. The width of the created granulation tissue was measured from microscopic observation at a magnification of 100×using image analysis program (Image-Pro version 3.0, Microsoft).
  • The thickness of the granulation tissue layer with only newly formed blood vessels was also measured. The newly formed blood vessels are those that grow from the basement of the tissue to the upper layer, i.e., longitudinally dissected blood vessels in the tissue.
  • In the case where sections were not of uniform thickness, those having the thickness in the middle of values list were taken. The values obtained were statistically analyzed by Student t-test.
  • As results, the granulation tissues of the test group were significantly thicker than those of the control group.
  • The trichrome staining revealed that the test group has very densely deposited collagen fibers, whereas the control group shows loose distribution of thin collagen fibers. In the test group, new blood vessels of the granulation tissues were created densely between the basement and the upper layer, indicating that the granulation tissues were grown actively. As contrast, the control group shows that a few of new blood vessels were found only at the basement of the granulation tissues, indicating that active development of the granulation tissues has not yet been initiated. See FIGS. 1A and 1B.
  • The thickness of the granulation tissues was measured under the microscope using 40× magnification. The results were statistically analyzed using Student's t-test (p<0.05). The test group showed 168.62 μm±16.06 which was significantly different from the control group of 59.44 μm±14.42 (p<0.01). The values were expressed as means+/− standard deviation (SD).
  • Experimental Example 2
  • Wound-Healing Effect of Human Blood Plasma Powder
  • The human blood plasma powder according to the present invention as prepared in Example 2 was applied to a full thickness defect wound to histologically study whether it promotes the formation of granulation tissue on the wound.
  • In accordance with the same manner as described in the above Experimental Example 1, ten adult white rats were subjected to full thickness defect wound. The two wounds on left side upper and lower limbs were treated with 0.05 g of the human blood plasma powder. As control, the right side two wounds were not treated. Then a dressing film (Tagaderm, 3M) was placed over the gauzed area, which was sewed up on all four sides by 5/0 nylon suture so as not to be detached over the experimental period.
  • On day 7 after the experiment, the stained granulation tissue sections were prepared and then the thickness thereof was histologically viewed and measured in accordance with the same manner as described in the above Experimental Example 1. As results, the granulation tissues of the test group were significantly thicker than those of the control group.
  • In the trichrome staining, whereas the control group showed loosely distributed thin collagen fibers, the test group showed dense deposited collagen fibers. The development of new blood vessels in the granulation tissues of the test group was similar to that of the above Experimental Example 1 in that they were created densely between the basement and the upper layer. See FIGS. 2A and 2B.
  • The thickness of the granulation tissues was measured under the microscope using 100× magnification. The results were statistically analyzed using Student's t-test (p<0.05). The test group showed 151.62 μm±14.24 which was significantly different from the control group of 44.24 μm±14.32 (p<0.01). The values were expressed as means+/−standard deviation (SD).
  • Experimental Example 3
  • wound-Healing Effect of Human Blood Plasma-Containing Ointment
  • The ointment containing human blood plasma according to the present invention as prepared in Example 3 was applied to a full thickness defect wound to histologically study whether it promotes the formation of granulation tissue on the wound.
  • In accordance with the same manner as described in the above Experimental Example 1, ten adult white rats were subjected to full thickness defect wound. The two wounds on left side upper and lower limbs were treated with 0.3 g of the ointment of the present invention. As control, the right side two wounds were treated with 0.3 g of SAM-A base (SAM-A Pharmaceutical Ind. Co., Ltd., Seoul, Korea). Then a dressing film (Tagaderm, 3M) was placed over the gauzed area, which was sewed up on all four sides by 5/0 nylon suture so as not to be detached over the experimental period.
  • On day 7 after the experiment, the stained granulation tissue sections were prepared and then the thickness thereof was histologically viewed and measured in accordance with the same manner as described in the above Experimental Example 1. As results, the granulation tissues of the test group were significantly thicker than those of the control group.
  • In the trichrome staining, whereas the control group showed loosely distributed thin collagen fibers, the test group showed dense deposited collagen fibers. The development of new blood vessels in the granulation tissues of the test group was similar to that of the above Experimental Example 1 in that they were created densely between the basement and the upper layer. See FIGS. 3A and 3B.
  • The thickness of the granulation tissues was measured under the microscope using 100× magnification. The results were statistically analyzed using Student's t-test (p<0.05). The test group showed 164.50 μm±17.64 which was significantly different from the control group of 54.54 μm±10.02 (p<0.01). The values were expressed as means+/−standard deviation (SD).
  • Experimental Examples 4 and 5
  • Wound-Healing Effect of Fetal Bovine Serum-Containing Ointment and Powder
  • These experiments were conduced to study the wound-healing effect of blood plasma derived from non-human animals. The abdomens of twenty adult white rats were subjected to full thickness defect wound. In accordance with the same manner as described in the above Experimental Example 2, the first group of 10 animals was treated with fetal bovine serum powder prepared in the above Example 5. In accordance with the same manner as described in the above Experimental Example 3, the second group of 10 animals was treated with fetal bovine serum powder prepared in the above Example 6.
  • On day 7 after the experiment, the stained granulation tissue sections were prepared and then the thickness thereof was histologically viewed and measured in accordance with the same manner as described in the above Experimental Examples 2 and 3. As results, the granulation tissues of the test group were significantly thicker than those of the control group.
  • In the trichrome staining, whereas the control group showed loosely distributed thin collagen fibers, the test group showed dense deposited collagen fibers. The development of new blood vessels in the granulation tissues of the test group was similar to that of the above Experimental Examples 2 and 3 in that they were created densely between the basement and the upper layer. See FIGS. 4A, 4B, 5A and 5B.
  • The thickness of the granulation tissues was measured under the microscope using 100× magnification. The results were statistically analyzed using Student's t-test (p<0.05). For the fetal bovine serum powder, the test group showed 152.62 μm±20.86 which was significantly different from the control group of 41.20 μm±7.44 (p<0.01).
  • For the fetal bovine serum-containing ointment, the test group showed 168.62 μm±19.26 which was significantly different from the control group of 58.62 μm±7.62 (p<0.01).
  • The values were expressed as means+/−standard deviation (SD).
  • Experimental Examples 6
  • Comparison of Wound-Healing Effects between Fetal Bovine Serum-Containing Ointment and PDGF Ointment
  • In this experiment, the wound-healing effect of the fetal bovine serum-containing ointment prepared in the above Example 6 according to the present invention was compared to that of the Regranex® (PDGF ointment, Johnson & Johnson) which was first approved as a wound-healing agent by the FDA.
  • Ten adult white rats were subjected to full thickness defect wound in accordance with the same manner as described in the above Experimental Example 3 except that two full thickness defect wounds were additionally formed along the middle line of the abdomen. While the two wounds on left side upper and lower limbs were treated with 0.3 g of the ointment of the present invention, the two wounds on right side upper and lower limbs were treated with 0.3 g of Regranex®. As control, the two wounds on the middle line of the abdomen were treated with SAM-A base (SAM-A Pharmaceutical Ind. Co., Ltd., Seoul, Korea).
  • On day 7 after the experiment, the stained granulation tissue sections were prepared and then the thickness thereof was histologically viewed and measured in accordance with the same manner as described in the above Experimental Example 2. As results, the granulation tissues of the Regranex®-treated group were thicker than those of the control group but were thinner than those of the test group. Moreover, the granulation tissues of the Regranex®-treated group were not dense.
  • The trichrome staining revealed that the Regranex®-treated group generated only few collagen fibers, which were not different from the control group. As contrast, the test group showed densely deposited collagen fibers which were as thick as those of normal dermis and were evenly distributed. For the new blood vessels of the granulation tissues, the Regranex®-treated group showed only few longitudinally growing blood vessels. As contrast, the test group showed new blood vessels of the granulation tissues which were densely created between the basement and the upper layer. See FIGS. 6A and 6B.
  • The thickness of the granulation tissues was measured under the microscope using 200× magnification. The results were statistically analyzed using Student's t-test (p<0.05). The test group showed 168.62 μm±13.41 which was significantly different from the Regranex®-treated group of 81.82 μm±18.01 (p<0.01). The values were expressed as means+/−standard deviation (SD).
  • Experimental Examples 7
  • Comparison of Wound-Healing Effects between Human Blood Plasma-Containing Ointment and PDGF Ointment
  • In this experiment, the wound-healing effect of the human blood plasma-containing ointment prepared in the above Example 3 according to the present invention was compared to that of the Regranex® (PDGF ointment, Johnson & Johnson). The abdomen of an adult white rat was subjected to four full thickness defect wounds. As control, the first upper wound was not treated with any agent but was well protected. The second wound was treated with 0.3 g of Regranex®. Each of the third and fourth wounds was treated with 0.3 g of the human blood plasma-containing ointment.
  • The third and fourth wounds treated with the human blood plasma-containing ointment were even more quickly healed compared to the first non-treated wound and the second Regranex®-treated wound. FIG. 7 shows photographs of the wound sites on days 4 and 11 after the initiation of treatment. It can be seen that the plasma-treated wounds (marked as Healadex) showed onset of healing by the 4th day and that by the 11th day, the wounds were almost healed.
  • Experimental Example 8
  • This experiment demonstrates the healing effect of the FBS-containing ointment as prepared in the above Example 6 according to the present invention on large wounds. The second-degree burn (partial thickness defect wound) was treated with the FBS-containing ointment of the present invention. FIG. 8 showed the extent of healing on days 1, 2 and 4 after treatment. The complete wound closure was viewed on day 4 after treatment.

Claims (16)

1. A pharmaceutical composition for the treatment of wounds, comprising a pharmaceutically effective amount of blood plasma as an active agent.
2. The pharmaceutical composition according to claim 1, wherein pH is in the range of 3.5 to 6.6
3. The pharmaceutical composition according to claim 1, wherein the active agent is derived from livestock.
4. The pharmaceutical composition according to claim 1, wherein it is topically administered.
5. The pharmaceutical composition according to claim 1, in the form of creams, ointments, gels, liquids or patched.
6. The pharmaceutical composition according to claim 1, wherein the wounds include contusion or bruise, non-healing traumatic wounds, the disruption by irradiation, abrasion, bone gangrene, laceration, avulsion, penetrated wound, gun shot wound, cutting, burn, cold sores, cutaneous ulcers, xeroderma, skin kefatosis, break, rupture, dermatitis, pain by dermatophyte, wounds by surgery or by vascular disorder, corneal wounds, pressure sore, bed sore, certain conditions associated with diabetes such as diabetic cutaneous disorder and with poor circulation, chronic ulcers, suture site caused by plastic surgery, spinal traumatic wounds, gynecological wounds, chemical wounds and acne.
7. The pharmaceutical composition according to claim 1, which is used at an amount of from 0.01 to 0.1 g/cm2 in the treatment of full thickness defect wounds.
8. A pharmaceutical composition for the treatment of wounds, comprising a pharmaceutically effective amount of blood serum as an active agent.
9. The pharmaceutical composition according to claim 8, wherein pH is in the range of 3.5 to 6.6
10. The pharmaceutical composition according to claim 8, wherein the active agent is derived from livestock.
11. The pharmaceutical composition according to claim 8, wherein it is topically administered.
12. The pharmaceutical composition according to claim 8, in the form of creams, ointments, gels, liquids or patched.
13. The pharmaceutical composition according to claim 8, wherein the wounds include contusion or bruise, non-healing traumatic wounds, the disruption by irradiation, abrasion, bone gangrene, laceration, avulsion, penetrated wound, gun shot wound, cutting, burn, cold sores, cutaneous ulcers, xeroderma, skin kefatosis, break, rupture, dermatitis, pain by dermatophyte, wounds by surgery or by vascular disorder, corneal wounds, pressure sore, bed sore, certain conditions associated with diabetes such as diabetic cutaneous disorder and with poor circulation, chronic ulcers, suture site caused by plastic surgery, spinal traumatic wounds, gynecological wounds, chemical wounds and acne.
14. The pharmaceutical composition according to claim 8, which is used at an amount of from 0.01 to 0.1 g/cm2 in the treatment of full thickness defect wounds.
15. The pharmaceutical composition according to claim 6, which is used at an amount of from 0.01 to 0.1 g/cm2 in the treatment of full thickness defect wounds.
16. The pharmaceutical composition according to claim 13, which is used at an amount of from 0.01 to 0.1 g/cm2 in the treatment of full thickness defect wounds.
US10/508,841 2002-05-09 2003-05-09 Pharmceutical composition for treatment of wounds conntaining blood plasma or serum Abandoned US20050142208A1 (en)

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Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030175410A1 (en) * 2002-03-18 2003-09-18 Campbell Phil G. Method and apparatus for preparing biomimetic scaffold
US20030180390A1 (en) * 2000-06-23 2003-09-25 Keum Ki Chang Agent for reduction of scar formation by using wound alkalinization
US20050136126A1 (en) * 2003-03-17 2005-06-23 Cambridgemed, Inc. Agent for reduction of scar formation by using wound alkalinization
US20060045853A1 (en) * 2002-07-09 2006-03-02 Kroon-Batenburg Louise M J Cross-beta structure comprising amyloid-binding proteins and methods for detection of the cross-beta structure, for modulating cross-beta structures fibril formation and for modulating cross-beta structure-mediated toxicity
US20060142198A1 (en) * 2004-07-02 2006-06-29 Wound Care Partners Llc Compositions for treating wounds and processes for their preparation
US20070003552A1 (en) * 2002-07-09 2007-01-04 Gebbink Martijn F B Cross-beta structure comprising amyloid binding proteins and methods for detection of the cross-beta structure, for modulating cross-beta structures fibril formation and for modulating cross-beta structure-mediated toxicity and method for interfering with blood coagulation
US20070015206A1 (en) * 2005-07-13 2007-01-18 Umc Utrecht Holding B.V. Method for detecting and/or removing protien comprising a cross-beta structure from a pharmaceutical composition
US20070048391A1 (en) * 2005-08-23 2007-03-01 Cambridgemed, Inc. Composition for reduction of scar formation on wound scar
US20070059377A1 (en) * 2005-08-22 2007-03-15 Freddo Mary E Compositions and methods for the treatment of wounds and the reduction of scar formation
US20070148142A1 (en) * 2002-05-09 2007-06-28 Cambridgemed, Inc. Pharmaceutical composition for treatment of wounds containing blood plasma or serum
US20080111272A1 (en) * 2006-10-17 2008-05-15 Burgess James E Method and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US20080118529A1 (en) * 2005-07-13 2008-05-22 Gebbink Martijn Frans Ben Gera Adjuvation Through Cross -Beta Structure
US20080267948A1 (en) * 2005-07-13 2008-10-30 Martijn Frans Ben Gerard Gebbink Croos-B Structure Binding Compounds
US20080286329A1 (en) * 2002-03-18 2008-11-20 Carnegie Mellon University Methods and Apparatus for Manufacturing Plasma Based Plastics and Bioplastics Produced Therefrom
US20090136587A1 (en) * 2005-08-11 2009-05-28 Medigenes Co., Ltd Pharmaceutical composition for the treatment of nerve damage comprising blood plasma or serum
US20090202980A1 (en) * 2005-03-21 2009-08-13 Crossbeta Biosciences B.V. Cross-Beta Structure Comprising Amyloid Binding Proteins and Methods for Detection of the Cross-Beta Structure, for Modulating Cross-Beta Structures Fibril Formation and for Modulating Cross-Beta Structure-Mediated Toxicity and Method for Interfering With Blood Coagulation
US20100015126A1 (en) * 2006-03-17 2010-01-21 Martijn Frans Ben Gerard Gebbink Methods of Binding of Cross-Beta Structures By Chaperones
US20100254900A1 (en) * 2002-03-18 2010-10-07 Campbell Phil G Biocompatible polymers and Methods of use
US20110008376A1 (en) * 2007-11-08 2011-01-13 Martijn Frans Ben Gerard Gebbink Immunogenic compositions capable of activating t-cells
US20110052564A1 (en) * 2007-11-08 2011-03-03 Martijn Frans Ben Gerard Gebbink Enhancement of immunogenicity of antigens
US20110064682A1 (en) * 2008-05-07 2011-03-17 Myeong Jin Nam Cosmetic composition comprising a stem-cell culture fluid, and a production method therefor
US8529959B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
WO2016036871A1 (en) * 2014-09-02 2016-03-10 Epien Medical, Inc. Formulation for treating chronic wounds
US10251911B2 (en) * 2009-09-16 2019-04-09 Entegrion, Inc. Spray dried human plasma

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100617648B1 (en) * 2005-02-25 2006-09-05 김응권 Pharmaceutical Composition for Treating Avellino Cornea Dystrophy Comprising Blood Plasma or Serum
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US20180371417A1 (en) * 2015-11-16 2018-12-27 Kenichi Yamahara Bovine serum composition and method for culturing cells using said bovine serum composition as additive

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5149691A (en) * 1991-03-12 1992-09-22 Creative Biomolecules, Inc. Issue repair and regeneration through the use of platelet derived growth factor (pdgf) in combination with dexamethasone
US5183805A (en) * 1990-08-13 1993-02-02 Board Of Regents, The University Of Texas System Bioactive egf peptides for promotion of tissue regeneration and cancer therapy
US5731298A (en) * 1992-01-03 1998-03-24 Reinmuller; Johannes Method for the treatment of scars and keloids
US5897880A (en) * 1995-09-29 1999-04-27 Lam Pharmaceuticals, Llc. Topical drug preparations
US5981606A (en) * 1991-03-01 1999-11-09 Warner-Lambert Company Therapeutic TGF-beta-wound healing compositions and methods for preparing and using same
US6048844A (en) * 1989-09-21 2000-04-11 Hyal Pharmaceutical Corporation Treatment of conditions and disease
US6165978A (en) * 1997-12-12 2000-12-26 University Of Southern California Wound healing composition
US20030180390A1 (en) * 2000-06-23 2003-09-25 Keum Ki Chang Agent for reduction of scar formation by using wound alkalinization
US20050136126A1 (en) * 2003-03-17 2005-06-23 Cambridgemed, Inc. Agent for reduction of scar formation by using wound alkalinization

Family Cites Families (148)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4006220A (en) 1975-06-04 1977-02-01 Gottlieb Sheldon K Compositions and methods useful for repairing depressed cutaneous scars
US4141973B1 (en) 1975-10-17 1989-08-08
EP0068048B1 (en) 1981-06-25 1985-06-19 Serapharm GmbH &amp; Co. KG Enriched plasma derivative for promoting wound sealing and wound covering
AT20824T (en) 1981-06-25 1986-08-15 Serapharm Gmbh & Co Kg Enriched plasma derivative for the assistance of wound closure and wound healing.
HU190723B (en) 1983-06-03 1986-10-28 Caola Kozmetikai Cosmetical composition containing protein-trace element adducts and process for producing them
US5166331A (en) 1983-10-10 1992-11-24 Fidia, S.P.A. Hyaluronics acid fractions, methods for the preparation thereof, and pharmaceutical compositions containing same
EP0171450A1 (en) 1984-08-14 1986-02-19 Österreichische Salen-Kunststoffwerk Gesellschaft m.b.H. Connection for plastic pipes and method of manufacture
US5409904A (en) 1984-11-13 1995-04-25 Alcon Laboratories, Inc. Hyaluronic acid compositions and methods
EP0202298B1 (en) * 1984-11-29 1992-07-15 Regents Of The University Of Minnesota Wound healing agents
US5165938A (en) 1984-11-29 1992-11-24 Regents Of The University Of Minnesota Wound healing agents derived from platelets
US4659572A (en) 1985-04-15 1987-04-21 Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of National Defence Burn wound dressing material
US4851521A (en) 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
IN166447B (en) 1985-11-27 1990-05-12 Ethicon Inc Method for the preparation of a sterile composition in the form of micro capsules
US4808576A (en) 1986-04-28 1989-02-28 Mobay Corporation Remote administration of hyaluronic acid to mammals
DK475386D0 (en) 1986-10-03 1986-10-03 Weis Fogh Ulla Sivertsen Method and apparatus for the production of biological substances
US5080893A (en) 1988-05-31 1992-01-14 University Of Florida Method for preventing surgical adhesions using a dilute solution of polymer
US4937270A (en) 1987-09-18 1990-06-26 Genzyme Corporation Water insoluble derivatives of hyaluronic acid
US4769234A (en) * 1987-10-06 1988-09-06 Peter M. Stephan Center Ltd. Skin care compositions containing polyvalent equine immune serum
US5209724A (en) 1988-04-11 1993-05-11 Dhaliwal Avtar S Composite anesthetic article and method of use
US4920104A (en) 1988-05-16 1990-04-24 Medchem Products, Inc. Sodium hyaluronate composition
US6010692A (en) 1988-05-31 2000-01-04 University Of Florida Research Foundation, Inc. Method and composition for preventing surgical adhesions and tissue damage
US5510418A (en) 1988-11-21 1996-04-23 Collagen Corporation Glycosaminoglycan-synthetic polymer conjugates
US5017900A (en) 1989-02-10 1991-05-21 Hitachi Mizusawa Electronics Co., Ltd. Deflection yoke
SE8900586L (en) 1989-02-21 1990-08-22 Pharmacia Ab Composition and foerfarande PROGRAM TO foerhindra adhesion kroppsvaevnader
US6271216B1 (en) 1989-07-24 2001-08-07 Allergan Stable solution of hyaluronate in a balanced salt medium
US5356883A (en) 1989-08-01 1994-10-18 Research Foundation Of State University Of N.Y. Water-insoluble derivatives of hyaluronic acid and their methods of preparation and use
US5196185A (en) 1989-09-11 1993-03-23 Micro-Collagen Pharmaceutics, Ltd. Collagen-based wound dressing and method for applying same
US5817642A (en) 1991-07-03 1998-10-06 Hyal Pharmaceutical Corporation Clearing of atherosclerosis
US6022866A (en) 1991-07-03 2000-02-08 Hyal Pharmaceutical Corporation Use of hyaluronic acid and forms to prevent arterial restenosis
US6087344A (en) 1991-07-03 2000-07-11 Hyal Pharmaceutical Corporation Formulations containing hyaluronic acid
US5972906A (en) 1991-07-03 1999-10-26 Hyal Pharmaceutical Corporation Treatment of mucous membrane disease, trauma or condition and for the relief of pain thereof
US5824658A (en) 1990-09-18 1998-10-20 Hyal Pharmaceutical Corporation Topical composition containing hyaluronic acid and NSAIDS
US5910489A (en) 1990-09-18 1999-06-08 Hyal Pharmaceutical Corporation Topical composition containing hyaluronic acid and NSAIDS
US5834444A (en) 1991-07-03 1998-11-10 Hyal Pharmaceutical Corporation Hyaluronic acid and salts thereof inhibit arterial restenosis
US5990095A (en) 1991-07-03 1999-11-23 Hyal Pharmaceutical Corporation Use of hyaluronic acid and forms to prevent arterial restenosis
US6103704A (en) 1991-07-03 2000-08-15 Hyal Pharmaceutical Corporation Therapeutic methods using hyaluronic acid
US5977088A (en) 1991-07-03 1999-11-02 Hyal Pharmaceutical Corporation Formulations containing hyaluronic acid
US5792753A (en) 1991-07-03 1998-08-11 Hyal Pharmaceutical Corporation Compositions comprising hyaluronic acid and prostaglandin-synthesis-inhibiting drugs
WO1994007505A1 (en) 1991-07-03 1994-04-14 Norpharmco Inc. Use of hyaluronic acid and forms to prevent arterial restenosis
JP2945993B2 (en) 1989-12-05 1999-09-06 武田薬品工業株式会社 External agent
US5095037B1 (en) 1989-12-21 1995-12-19 Nissho Kk Combined anti-inflammatory agent
JPH0561253B2 (en) 1990-02-20 1993-09-06 Hoechst Japan
US5017229A (en) 1990-06-25 1991-05-21 Genzyme Corporation Water insoluble derivatives of hyaluronic acid
SE501217C2 (en) 1990-12-06 1994-12-12 Skandigen Ab Cell proliferation matrix and use thereof
GR1002610B (en) 1991-01-02 1997-02-20 Johnson & Johnson Consumer Products Inc. Wound healing compositions containing fibroplast growth factor and ascorbic acid
DK0497724T3 (en) 1991-01-26 1996-04-29 Senju Pharma Co An agent for disintegrating gallstones
GR920100122A (en) 1991-04-05 1993-03-16 Ethicon Inc Ionically crosslinked carboxyl-containing polysaccharides for adhension prevention.
US5234914A (en) 1991-06-11 1993-08-10 Patent Biopharmaceutics, Inc. Methods of treating hemorrhoids and anorecial disease
SE9101853D0 (en) 1991-06-17 1991-06-17 Jonas Wadstroem Improved tissue ashesive
CA2071137A1 (en) 1991-07-10 1993-01-11 Clarence C. Lee Composition and method for revitalizing scar tissue
US7060287B1 (en) 1992-02-11 2006-06-13 Bioform Inc. Tissue augmentation material and method
CA2061703C (en) 1992-02-20 2002-07-02 Rudolf E. Falk Formulations containing hyaluronic acid
US6136793A (en) 1992-02-20 2000-10-24 Hyal Pharmaceutical Corporation Formulations containing hyaluronic acid
US5639738A (en) 1992-02-20 1997-06-17 Hyal Pharmaceutical Corporation Treatment of basal cell carcinoma and actinic keratosis employing hyaluronic acid and NSAIDs
US6218373B1 (en) 1992-02-20 2001-04-17 Hyal Pharmaceutical Corporation Formulations containing hyaluronic acid
US6114314A (en) 1992-02-21 2000-09-05 Hyal Pharmaceutical Corp. Formulations containing hyaluronic acid
IL101056A (en) 1992-02-24 1997-03-18 Res & Dev Co Ltd Composition for nasal treatment
GB9205800D0 (en) 1992-03-17 1992-04-29 British Tech Group Treatment of fibrotic disorders
FR2695561B1 (en) 1992-09-17 1994-12-02 Lvmh Rech Gie Cosmetic or dermatological composition containing at least one saponin ginsenoside type and its applications, including hair care.
US5529987A (en) 1993-08-04 1996-06-25 Patent Biopharmaceutics, Inc. Hyaluronic acid-urea pharmaceutical compositions and uses
US5550112A (en) 1992-12-30 1996-08-27 Patent Biopharmaceutics, Inc. Hyaluronic acid-urea pharmaceutical compositions and uses
US5681825A (en) 1993-03-15 1997-10-28 Lindqvist; Bengt Surgical method
AU674061B2 (en) 1993-03-30 1996-12-05 Hoechst Japan Limited Factor XIII for treatment of skin wounds
US5744449A (en) 1993-05-10 1998-04-28 Lipps; Binie V. Lethal toxin neutralizing factors
IT1263394B (en) 1993-07-30 1996-08-05 Fidia Advanced Biopolymers Srl Pharmaceutical compositions for topical use based on hyaluronic acid and its derivatives
RU2082415C1 (en) 1993-08-16 1997-06-27 Виктор Алексеевич Кольцов Method for tissue healing
US5356683A (en) 1993-10-28 1994-10-18 Rohm And Haas Company Expandable coating composition
IL107578A (en) 1993-11-11 1998-07-15 Yissum Res Dev Co Topical antibacterial preparation comprising silver sulfadiazine and collagen
JPH07267992A (en) 1994-03-31 1995-10-17 Hoechst Japan Ltd New protein phbp-70
US5604200A (en) 1994-05-02 1997-02-18 Taylor-Mccord; Darlene Wound therapeutic mixture containing medical grade hyaluronic acid and tissue culture grade plasma-fibronectin in a delivery system that creates a moist environment which simulates in utero healing
US6294202B1 (en) 1994-10-06 2001-09-25 Genzyme Corporation Compositions containing polyanionic polysaccharides and hydrophobic bioabsorbable polymers
JP4010574B2 (en) 1994-12-05 2007-11-21 電気化学工業株式会社 External preparation for skin
US5585007A (en) 1994-12-07 1996-12-17 Plasmaseal Corporation Plasma concentrate and tissue sealant methods and apparatuses for making concentrated plasma and/or tissue sealant
US5733545A (en) * 1995-03-03 1998-03-31 Quantic Biomedical Partners Platelet glue wound sealant
US5925656A (en) 1995-04-10 1999-07-20 Dr. Reddy's Research Foundation Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US5641483A (en) 1995-06-07 1997-06-24 Beaulieu; Andre Wound healing formulations containing human plasma fibronectin
US5591444A (en) 1995-07-28 1997-01-07 Isolagen Technologies, Inc. Use of autologous dermal fibroblasts for the repair of skin and soft tissue defects
DE69634823D1 (en) 1995-08-29 2005-07-14 Fidia Advanced Biopolymers Srl From hyaluronic acid derivatives existing biomaterials for inhibition of post-operative adhesion formation
US6387407B1 (en) 1995-09-29 2002-05-14 L.A.M. Pharmaceutical Corporation Topical drug preparations
JPH09124453A (en) * 1995-11-02 1997-05-13 Japan Happy:Kk Dermal preparation for external use
IT1282219B1 (en) 1995-12-20 1998-03-16 Fidia Advanced Biopolymers Srl combined physical chemical process for the preparation of hyaluronic acid fractions with a low molecular weight characterized by low
IT1287227B1 (en) 1996-04-04 1998-08-04 Fidia Spa In Amministrazione S hyaluronic acid as a corneal preservation of the liquid component
IT1288290B1 (en) 1996-06-21 1998-09-11 Fidia Spa In Amministrazione S crosslinked hyaluronic acid and related pharmaceutical compositions for the treatment of arthropathies
US5866554A (en) 1996-07-19 1999-02-02 Shalaby; Shalaby W. Compositions for prevention of inflammation and adhesion formation and uses thereof
US6037331A (en) 1996-07-19 2000-03-14 Poly-Med, Inc. Compositions for prevention of inflammation and adhesion formation uses thereof
US6541460B2 (en) 1996-08-07 2003-04-01 George D. Petito Method for use of hyaluronic acid in wound management
WO1998022587A2 (en) 1996-11-21 1998-05-28 Cedars-Sinai Medical Center Pituitary-tumor-transforming-genes, and related products
US6063406A (en) 1997-04-18 2000-05-16 Chemcraft, Inc. Skin care compositions
US6596703B1 (en) 1997-07-11 2003-07-22 Jagotec Ag Promotion of wound healing utilizing steroids having reduced deteriorous systemic side effects typical of glucocorticoids, mineralocorticoids and sex steroids
CA2301018C (en) 1997-08-22 2006-06-20 Denki Kagaku Kogyo Kabushiki Kaisha Hyaluronic acid gel, method of its production and medical material containing it
FR2770779B1 (en) 1997-11-10 2000-07-21 Bernstein Veronique Solute hypotonic or hypoosmolar plasma used in the treatment of cellulite, fibroses, and hirsutism
US6171611B1 (en) 1997-11-12 2001-01-09 Dante J. Picciano Iodine-containing nasal moisturizing saline and mouthwash solutions
US20020025921A1 (en) 1999-07-26 2002-02-28 Petito George D. Composition and method for growing, protecting, and healing tissues and cells
US7691829B2 (en) 1998-03-24 2010-04-06 Petito George D Composition and method for healing tissues
IT1301994B1 (en) 1998-08-05 2000-07-20 Jasper Ltd Liability Co Derivatives of hyaluronic acid.
EP1129683A4 (en) 1998-11-10 2002-06-19 Denki Kagaku Kogyo Kk Hyaluronic acid gel, process for the preparation thereof and medical materials containing the same
DK172900B1 (en) 1998-12-18 1999-09-27 Per Julius Nielsen Preparation and kit for use in intraocular operations
IT1302534B1 (en) 1998-12-21 2000-09-05 Fidia Advanced Biopolymers Srl Compositions injectable, biocompatible and biodegradable comprendentialmeno one hyaluronic acid derivative, chondrogenic cells, for
ES2243232T3 (en) 1999-02-23 2005-12-01 Angiotech International Ag Compositions and methods for improving the integrity of body cavities and vias compromised.
US7015198B1 (en) 1999-05-11 2006-03-21 Orentreich Foundation For The Advancement Of Science, Inc. Materials for soft tissue augmentation and methods of making and using same
US6521223B1 (en) 2000-02-14 2003-02-18 Genzyme Corporation Single phase gels for the prevention of adhesions
US6262020B1 (en) 2000-02-15 2001-07-17 Alphamed Pharmaceuticals Corp. Topical wound therapeutic compositions
US6573249B2 (en) 2000-02-15 2003-06-03 Alphamed Pharmaceutical Corp. Topical wound therapeutic compositions
US6828308B2 (en) 2000-07-28 2004-12-07 Sinclair Pharmaceuticals, Ltd. Compositions and methods for the treatment or prevention of inflammation
IT1318649B1 (en) 2000-07-28 2003-08-27 Propharma S R L Ora Sinclair P Pharmaceutical compositions for the treatment of mucositis and stomatitis.
US20030211166A1 (en) 2001-07-31 2003-11-13 Yamamoto Ronald K Microparticulate biomaterial composition for medical use
US7144729B2 (en) 2000-09-01 2006-12-05 Dfb Pharmaceuticals, Inc. Methods and compositions for tissue regeneration
US6924273B2 (en) 2000-10-03 2005-08-02 Scott W. Pierce Chondroprotective/restorative compositions and methods of use thereof
CN1156042C (en) 2001-03-20 2004-06-30 北京科海迈迪生物技术有限责任公司 Process for preparing nm-class alpha-phase nickel hydroxide used as electrode material
US20030007957A1 (en) 2001-07-03 2003-01-09 Calvin Britton Novel wound healing composition not containing bovine-derived activating reagents
US20030152639A1 (en) 2001-07-03 2003-08-14 Calvin Britton Novel wound healing composition not containing bovine-derived activating reagents
US7008626B2 (en) 2001-11-05 2006-03-07 Seikagaku Corporation Medical composition for protuberance of epithelium
US20030187381A1 (en) 2001-12-28 2003-10-02 Genzyme Corporation Bioresorbable foam packing device and use thereof
CZ12015U1 (en) 2002-01-18 2002-04-17 Cpn Spol. S R.O. Preparation for preventing adhesion of a bandage to a wound
US20030147830A1 (en) 2002-01-30 2003-08-07 The Procter & Gamble Company Topical skin and/or hair compositions containing protein
AU2003221078A1 (en) 2002-04-08 2003-10-20 Denki Kagaku Kogyo Kabushiki Kaisha Therapeutic composition for bone infectious disease
DE60221227T2 (en) 2002-04-30 2008-01-31 Sifi S.P.A., Lavinaio-Aci Xanthan gum-containing pharmaceutical preparations reepithelialisierende
US20050142208A1 (en) 2002-05-09 2005-06-30 Won Min Yoo Pharmceutical composition for treatment of wounds conntaining blood plasma or serum
JP2005533076A (en) 2002-06-20 2005-11-04 ノバルテイス・コンシユーマー・ヘルス・エス・アー Nasal compositions comprising a mucopolysaccharide and propylene glycol
ITMI20021866A1 (en) 2002-08-30 2004-02-29 Luigi Allegra A pharmaceutical preparation in colloidal form useful in the treatment of skin affections.
AU2003279730A1 (en) 2002-09-30 2004-04-19 Fibrogen, Inc. Dry tissue sealant compositions
DE10246340A1 (en) 2002-10-04 2004-04-29 Wohlrab, David, Dr. Combination preparation of hyaluronic acid and at least one local anesthetic and its use
US20040092482A1 (en) 2002-11-07 2004-05-13 Gupta Shyam K. Hydroxy acids based delivery systems for skin resurfacing and anti-aging compositions
US20040180622A1 (en) 2003-03-11 2004-09-16 Godfrey Timothy Gordon Coordinating multiple air-interface subsystems that serve a common host
US20040197319A1 (en) 2003-03-24 2004-10-07 Paul Harch Wound healing composition derived from low platelet concentration plasma
WO2004104166A2 (en) 2003-05-07 2004-12-02 La Jolla Institute For Molecular Medicine Administration of hyaluronic acid to enhance the function of transplanted stem cells
US7262179B2 (en) 2003-05-28 2007-08-28 Bristol-Myers Squibb Company Wound care compositions
ES2226567B1 (en) 2003-06-20 2006-07-01 Universidad De Santiago De Compostela Nanoparticles of hyaluronic acid.
ITMI20031291A1 (en) 2003-06-25 2004-12-26 Ricerfarma Srl Use of hyaluronic acid for the preparation of compositions for the treatment of ulcers of the oral cavity.
DE20318634U1 (en) 2003-11-13 2004-02-26 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh Topical compositions for preventing or treating rhinitis, comprising sympathomimetic agent with vasoconstrictive and/or mucosal swelling reducing action and glycosaminoglycan to reduce side-effects
US8124120B2 (en) 2003-12-22 2012-02-28 Anika Therapeutics, Inc. Crosslinked hyaluronic acid compositions for tissue augmentation
US20050142161A1 (en) 2003-12-30 2005-06-30 Freeman Lynetta J. Collagen matrix for soft tissue augmentation
WO2005072751A1 (en) 2004-01-28 2005-08-11 The Regents Of The University Of California Novel interstitial therapy for immediate symptom relief and chronic therapy in interstitial cystitis
CN1270812C (en) 2004-02-04 2006-08-23 刘寿山 Utrafiltration apparatus and its operation guide
US20050191286A1 (en) 2004-02-09 2005-09-01 Gandy James B. Lyophilized platelet rich plasma for the use in wound healing (chronic or acute) and bone or tissue grafts or repair
US20050180938A1 (en) 2004-02-17 2005-08-18 Beatrice Novelli Skin care cosmetic regime and kit
US20050220882A1 (en) 2004-03-04 2005-10-06 Wilson Pritchard Materials for medical implants and occlusive devices
US7956180B2 (en) 2004-05-27 2011-06-07 Novozymes A/S Dried and agglomerated hyaluronic acid product
US20050272695A1 (en) 2004-05-27 2005-12-08 Novozymes Biopolymer A/S Fast dissolving dried hyaluronic acid product
US20060040895A1 (en) 2004-08-19 2006-02-23 Kipling Thacker Aesthetic use of hyaluronan
MX2007004120A (en) * 2004-10-07 2007-06-15 Duramed Pharmaceuticals Inc Methods of hormonal treatment utilizing ascending-dose extended cycle regimens.
US20060194759A1 (en) 2005-02-25 2006-08-31 Eidelson Stewart G Topical compositions and methods for treating pain and inflammation
US7399783B2 (en) 2005-06-22 2008-07-15 The Quigley Corporation Methods for the treatment of scar tissue
US7491709B2 (en) 2005-07-01 2009-02-17 Wayne Carey Treatment with hyaluronic acid
US7323184B2 (en) 2005-08-22 2008-01-29 Healagenics, Inc. Compositions and methods for the treatment of wounds and the reduction of scar formation
US20070048391A1 (en) 2005-08-23 2007-03-01 Cambridgemed, Inc. Composition for reduction of scar formation on wound scar
US20070048387A1 (en) 2005-09-01 2007-03-01 Edwards Jeffrey D Tissue disruption treatment and composition for use thereof
US20070087061A1 (en) 2005-10-14 2007-04-19 Medafor, Incorporated Method and composition for creating and/or activating a platelet-rich gel by contact with a porous particulate material, for use in wound care, tissue adhesion, or as a matrix for delivery of therapeutic components

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6048844A (en) * 1989-09-21 2000-04-11 Hyal Pharmaceutical Corporation Treatment of conditions and disease
US20040019011A1 (en) * 1989-09-21 2004-01-29 Falk Rudolf Edgar Treatment of conitions and disease
US5183805A (en) * 1990-08-13 1993-02-02 Board Of Regents, The University Of Texas System Bioactive egf peptides for promotion of tissue regeneration and cancer therapy
US5981606A (en) * 1991-03-01 1999-11-09 Warner-Lambert Company Therapeutic TGF-beta-wound healing compositions and methods for preparing and using same
US5376636A (en) * 1991-03-12 1994-12-27 Creative Biomolecules, Inc. Method for promoting tissue repair and regeneration using PDGF and glucocorticoids
US5149691A (en) * 1991-03-12 1992-09-22 Creative Biomolecules, Inc. Issue repair and regeneration through the use of platelet derived growth factor (pdgf) in combination with dexamethasone
US5731298A (en) * 1992-01-03 1998-03-24 Reinmuller; Johannes Method for the treatment of scars and keloids
US5897880A (en) * 1995-09-29 1999-04-27 Lam Pharmaceuticals, Llc. Topical drug preparations
US6165978A (en) * 1997-12-12 2000-12-26 University Of Southern California Wound healing composition
US20030180390A1 (en) * 2000-06-23 2003-09-25 Keum Ki Chang Agent for reduction of scar formation by using wound alkalinization
US20050136126A1 (en) * 2003-03-17 2005-06-23 Cambridgemed, Inc. Agent for reduction of scar formation by using wound alkalinization

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030180390A1 (en) * 2000-06-23 2003-09-25 Keum Ki Chang Agent for reduction of scar formation by using wound alkalinization
US7255883B2 (en) 2000-06-23 2007-08-14 Healagenics, Inc. Agent for reduction of scar formation by using wound alkalinization
US20100254900A1 (en) * 2002-03-18 2010-10-07 Campbell Phil G Biocompatible polymers and Methods of use
US8529956B2 (en) 2002-03-18 2013-09-10 Carnell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US20030175410A1 (en) * 2002-03-18 2003-09-18 Campbell Phil G. Method and apparatus for preparing biomimetic scaffold
US20080286329A1 (en) * 2002-03-18 2008-11-20 Carnegie Mellon University Methods and Apparatus for Manufacturing Plasma Based Plastics and Bioplastics Produced Therefrom
US8529960B2 (en) 2002-03-18 2013-09-10 Carnell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8017157B2 (en) 2002-05-09 2011-09-13 Osiris Therapeutics, Inc. Method of treating a wound with acidified plasma or serum
US20070148142A1 (en) * 2002-05-09 2007-06-28 Cambridgemed, Inc. Pharmaceutical composition for treatment of wounds containing blood plasma or serum
US20060045853A1 (en) * 2002-07-09 2006-03-02 Kroon-Batenburg Louise M J Cross-beta structure comprising amyloid-binding proteins and methods for detection of the cross-beta structure, for modulating cross-beta structures fibril formation and for modulating cross-beta structure-mediated toxicity
US20070003552A1 (en) * 2002-07-09 2007-01-04 Gebbink Martijn F B Cross-beta structure comprising amyloid binding proteins and methods for detection of the cross-beta structure, for modulating cross-beta structures fibril formation and for modulating cross-beta structure-mediated toxicity and method for interfering with blood coagulation
US8158585B2 (en) 2002-07-09 2012-04-17 Crossbeta Biosciences B.V. Cross-β structure comprising amyloid-binding proteins and methods for detection of the cross-β structure, for modulating cross-β structures fiber formation and modulating cross-β structure-mediated toxicity
US20050136126A1 (en) * 2003-03-17 2005-06-23 Cambridgemed, Inc. Agent for reduction of scar formation by using wound alkalinization
US20060142198A1 (en) * 2004-07-02 2006-06-29 Wound Care Partners Llc Compositions for treating wounds and processes for their preparation
US20090202980A1 (en) * 2005-03-21 2009-08-13 Crossbeta Biosciences B.V. Cross-Beta Structure Comprising Amyloid Binding Proteins and Methods for Detection of the Cross-Beta Structure, for Modulating Cross-Beta Structures Fibril Formation and for Modulating Cross-Beta Structure-Mediated Toxicity and Method for Interfering With Blood Coagulation
US20080118529A1 (en) * 2005-07-13 2008-05-22 Gebbink Martijn Frans Ben Gera Adjuvation Through Cross -Beta Structure
US20080267948A1 (en) * 2005-07-13 2008-10-30 Martijn Frans Ben Gerard Gebbink Croos-B Structure Binding Compounds
US20080207488A1 (en) * 2005-07-13 2008-08-28 Gebbink Martijn Frans Ben Gera Method for Detecting Peptides Comprising a Cross-B Structure
US8114832B2 (en) * 2005-07-13 2012-02-14 Crossbeta Biosciences B.V. Method for detecting and/or removing a protein comprising a cross-beta structure from a pharmaceutical composition
US20070015206A1 (en) * 2005-07-13 2007-01-18 Umc Utrecht Holding B.V. Method for detecting and/or removing protien comprising a cross-beta structure from a pharmaceutical composition
US8067187B2 (en) 2005-07-13 2011-11-29 Crossbeta Biosciences B.V. Cross-β structure binding compounds
US20090136587A1 (en) * 2005-08-11 2009-05-28 Medigenes Co., Ltd Pharmaceutical composition for the treatment of nerve damage comprising blood plasma or serum
US20070059377A1 (en) * 2005-08-22 2007-03-15 Freddo Mary E Compositions and methods for the treatment of wounds and the reduction of scar formation
US20070048391A1 (en) * 2005-08-23 2007-03-01 Cambridgemed, Inc. Composition for reduction of scar formation on wound scar
US20100015126A1 (en) * 2006-03-17 2010-01-21 Martijn Frans Ben Gerard Gebbink Methods of Binding of Cross-Beta Structures By Chaperones
US20080111272A1 (en) * 2006-10-17 2008-05-15 Burgess James E Method and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8529961B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8293530B2 (en) 2006-10-17 2012-10-23 Carnegie Mellon University Method and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8529959B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8529958B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8911789B2 (en) 2006-10-17 2014-12-16 Carnegie Mellon University Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US9364503B2 (en) 2006-10-17 2016-06-14 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US20110008376A1 (en) * 2007-11-08 2011-01-13 Martijn Frans Ben Gerard Gebbink Immunogenic compositions capable of activating t-cells
US20110052564A1 (en) * 2007-11-08 2011-03-03 Martijn Frans Ben Gerard Gebbink Enhancement of immunogenicity of antigens
US20110064682A1 (en) * 2008-05-07 2011-03-17 Myeong Jin Nam Cosmetic composition comprising a stem-cell culture fluid, and a production method therefor
US10251911B2 (en) * 2009-09-16 2019-04-09 Entegrion, Inc. Spray dried human plasma
WO2016036871A1 (en) * 2014-09-02 2016-03-10 Epien Medical, Inc. Formulation for treating chronic wounds

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