MX2007007072A - Agents for controlling biological fluids and methods of use thereof - Google Patents

Abstract

Therapeutic formulations adapted for positive-pressure application for controlling biological fluid at a desired site in a subject, absorbent articles comprising therapeutic formulations, and anti-infective devices coated with therapeutic formulations, said formulations comprising about 25%to about 99%by weight liquid-crystal forming compound and 0%to about 75%by weight solvent. In addition, methods of using said formulations including methods for controlling biological fluid at a desired site in a subject, methods for controlling blood loss, and methods for facilitating effective closure of a vascular wound or incision site at a desired site in a subject are disclosed, the methods comprising administering particular formulations comprising liquid-crystal forming compounds and solvents that are described herein.

Description

AGENTS TO CONTROL BIOLOGICAL FLUIDS AND METHODS OF USING THEMSELVES FIELD OF THE TECHNIQUE The present invention relates to compositions which are hydrophobic or amphiphilic and liquid crystalline formulations and methods for use as adjunct surgical therapies, hemostatic agents, and as primary treatment modalities for hard and soft tissue wounds as well as the basis of cosmetic medical devices.

BACKGROUND OF THE INVENTION The use of hemostatic agents and devices is a common practice in modern surgery. The general field has a range of use of agents that exhibit local action by the physical presence of the agent such as astringents (aluminum and magnesium salts), hydrolyzed gelatin (Gelfoam® Pharmacia) and oxidized cellulose (Surgicel® Johnson &Johnson ) to products that seek to exploit physiological mechanisms such as systems based on thrombin and fibrin. However, the field is plagued with formulations of limited efficiency and systems that finally expose patients to a higher risk of adverse immune response. Formulations that can be applied in a variety of physical states to quickly and reliably establish hemostasis without the risk of secondary immune responses could be highly desirable and of great commercial interest.

BRIEF DESCRIPTION OF THE INVENTION In a first embodiment of the invention there is provided a therapeutic formulation adapted for application at positive and effective pressure to control the biological fluid at a desired site in a subject, the formulation comprising about 25% to about 99% by weight of a compound that liquid crystal form and 0% to about 75% by weight of solvent, wherein the formulation effectively controls the biological fluid at the desired site in the subject. In related embodiments, the solvent may be a polar solvent, a non-polar solvent, a semi-polar solvent or a combination thereof, and the particular formulations may comprise about 97% of the liquid crystal forming compound and about 3% solution normal saline; about 65% of the compound that forms liquid crystal and about 15% of normal saline; about 35% of the compound that forms liquid crystal and about 65% of normal saline; approximately 92.5% hyaluronate; about 95% of the liquid crystal forming compound and about 5% isopropyl myristate; about 95% of the compound that forms liquid crystal and about 5% of ethanol 190 of alcoholic strength; or about 80% of the compound that forms liquid crystal and about 20% of cottonseed oil. Other particular embodiments may comprise platelets, platelet-rich plasma, plasma or whole blood, in addition to, or instead of, the aforementioned solvents. Some particular embodiments may thus comprise about 97% of the compound that forms liquid crystal and about 3% of whole blood; about 80% of the compound that forms liquid crystal and about 9% of whole blood; about 65% of the compound that forms liquid crystal and about 15% of whole blood; about 35% of the compound that forms liquid crystal and about 25% of blood plasma, about 97% of the compound that forms liquid crystal and about 3% of blood plasma; about 65% of the compound that forms liquid crystal and about 15% of blood plasma; or about 35% of the compound that forms liquid crystal and about 25% of blood plasma. In another embodiment, an absorbent article is provided comprising an absorbent layer and an effective formulation for controlling the biological fluid of a human or veterinary subject, wherein the formulation comprises from about 25% to 99% by weight of a crystal-forming compound. liquid and from about 0% to 75% by weight of solvent and is present within or in at least a portion of the article. The related embodiments may comprise an absorbent layer that additionally includes an absorbent additive; an outer layer permeable to liquid and permeable to moisture vapor having an inner surface and an outer surface, the internal surface essentially coextensive with an outer surface of the absorbent layer; an outer layer impervious to liquid and permeable to moisture vapor having an inner surface and an outer surface, the inner surface essentially coextensive with an outer surface of the absorbent layer; an absorbent article additionally comprises an outer layer impervious to liquid and impervious to moisture vapor having an inner surface and an outer surface, the internal surface essentially coextensive with an outer surface of the absorbent layer; a liquid permeable coating, adapted not to be adherent to a wound, having a surface that is substantially coextensive with an inner surface of the absorbent layer such that the absorbent layer is located between the liquid permeable coating and the outer layer; or any combination thereof. In other embodiments, the effective composition for controlling biological fluids in the article provides utility as an anti-adherent between the article and the body tissue to assist in the placement or removal of the article from a use site thus reducing the trauma of the application or removal of said article, and the biological fluid controlling the formulation can be applied to the article by spray coating, hot melt coating, dip coating, direct transfer, manual application or a combination thereof. The specific embodiments provide an article that can be any of a wound dressing, a medical sponge, a hemostatic article, a haemostatic nose article, an adhesive bandage, a wound protective material, a protective material for internal vascular closure, a bandage for external vascular closure, a swellable absorbent article, an article of fibrotic wound protective material, or a feminine hygiene product, and the liquid crystal forming compound can be any of a fatty acid ester, an polyethylene, a glycolipid, a polyester, a polyethylene glycol, or a combination thereof. In related embodiments, the fatty acid ester can be a monoester, diester, triester or mixture thereof, and the monoester can be glyceryl monoarachidonate, glyceryl monolaurate, glyceryl monolinoleate, glyceryl monolinolenate, glyceryl monomiristate, glyceryl monopalmitoleate, glyceryl monooleate, and glyceryl monostearate; isopropyl monoarachidonate, isopropyl monolaurate, isopropyl monolinoleate, isopropyl monolinolenate, isopropyl monomistista, isopropyl monopalmitoleate, isopropyl monooleate, and isopropyl monostearate; methyl monoarachidonate, methyl monolaurate, methyl monolinoleate, methyl monolinolenate, methyl monomiristate, methyl monopalmitoleate, methyl monooleate, and methyl monostearate; and propylene glycyl monoarachidonate, propylene glycyl monolaurate, propylene glycol monolinoleate, propylene glycol monolinolenate, propylene glycyl monomyistate, propylene glycol monopalmitoleate, monooleate, and propylene glycyl monostearate, or a combination thereof. Another particular embodiment provides an infection resistant device, the device is treated with an anti-infective formulation comprising approximately 25% to 99% by weight of fatty acid or fatty acid ester, wherein said anti-infective formulation inhibits the formation of growth of the pathogen in the device, or in adjacent tissues, thereby imparting resistance to the infection to the device. In related embodiments, the anti-infective formulation may additionally comprise from about 0% to 75% solvent and the fatty acid or fatty acid ester may be a compound that forms liquid crystal, and in some embodiments, after the formation of a liquid crystal, the anti-infectious formulation thus decreases migration within or in the body tissues and attenuates the removal of the formulation from the placement site, or a site adjacent to or near where the device is placed within a subject. In even other embodiments, the liquid crystal formulation can act as a delivery system for controlled release of the degradation products from the formulation, wherein said degradation products provide an additional anti-infective effect. Related modalities provide a device that is effective for the treatment of an acute or chronic wound, and the acute wound may be an abrasion, burn, laceration, puncture or incision, and the chronic wound may be an ulcer including a leg ulcer , decubitus, fungal, diabetic, gastric, foot, sacral or indolent ulcer. In other embodiments, the device can be effective as a tissue void fill created by a trauma, disease or surgical procedure, and in other embodiments, the device can be treated with an anti-infective formulation by spray coating, hot melt coating, dip coating or a combination thereof before use. In some embodiments, the device may be composed of organic material, inorganic material, or a combination thereof, and in other embodiments, the device may be a catamenial absorption device, condom, prophylactic, medicinal sponge, surgical bandage, bandage for wound, adhesive bandage or a combination thereof. Alternatively, the device may be a prosthetic, an implant or a combination thereof. In related modalities, the type of prosthetic or implant may be a type of prosthetic or spinal, orthopedic, dental, cardiac, neural, or cosmetic implant, or a combination thereof. In particular modalities, the prosthetic or orthopedic implant may be an artificial joint, hardware for fracture repair, artificial cartilage, a plate, a screw, a nail, a wire or a combination thereof; The prosthetic or dental implant can be a root form, a Ramus type frame, a transosseous implant, a razor shape, hardware for fracture repair, a prosthetic device, general hardware, a plate, a screw, a nail, a wire or a combination thereof; the prosthetic or cardiac implant can be a pacemaker, a defibrillator, a cardiac valve, a vascular graft or a combination thereof; and the prosthetic or cosmetic implant may be a breast implant, a dermal filler, a tissue vacuum filler, a gluteal implant, a facial implant or a combination thereof. Even other embodiments provide an infection resistant device, the device is treated with an anti-infective formulation wherein the anti-infective formulation comprises about 25% to 99% of the liquid crystal forming compound, about 0% to 50% acid fatty and about 0% to 50% solvent, by weight; about 90% of the liquid crystal forming compound, about 5% lauric acid and about 5% solvent by weight; about 65% of the liquid crystal forming compound, about 10% myristic acid and about 25% solvent, by weight; or about 35% of the liquid crystal forming compound, about 15% palmitic and about 40% solvent, by weight. Another embodiment provides an effective hemostatic formulation for controlling bleeding at a desired site in a human or veterinarian subject, the composition comprising from 25% to about 99% by weight of a compound that forms liquid crystal and from 0% to about 75% by weight of solvent, where the hemostatic formulation is adapted for application to positive pressure in or within the tissue, affects hemostasis and induces total effects at the desired site in approximately 15 minutes or less, thus controlling bleeding. More particularly, hemostasis can be affected and local effects induced at the site in about 10 minutes or less of application, even more particularly in about 5 minutes or less of application, even more particularly in about 2 minutes or less of application, and even more particularly in about 30 seconds or less of application. In related embodiments of a hemostatic formulation, the solvent can be any of an alcohol, polyethylene glycol, propylene glycol, polypropylene glycol, water, isotonic aqueous solution, biological fluid, a system with physiological pH, urine, saliva, serous fluid, synovial fluid, gastric secretions cerebrospinal fluid, vitreous humor, lymph, wound exudate, cholesterol, a system with physiological pH or combinations thereof; the liquid crystal forming compound can be any of a fatty acid, fatty acid monoester, fatty acid diester, fatty acid triester or combinations thereof further comprising at least one unsaturated carbon-carbon bond. More particularly, the liquid crystal forming agent can be a glyceryl monoester, diester, triester, or combinations thereof, and even more particularly, the liquid crystal forming compound can be glyceryl monooleate. Yet another embodiment provides a formulation for a thrombin inhibitor comprised of from about 25 to 99% by weight of a liquid crystal forming compound and about 0% to 75% by weight of solvent, wherein the formulation is adapted for positive pressure application. a desired site in a subject. In related embodiments, the liquid crystal forming compound can be a fatty acid ester. More particularly, the formulation of the thrombin inhibitor can be effective as a tissue void filler, such as those created by a trauma, disease or surgical procedure, and more particularly, the formulation of the thrombin inhibitor can be a neuroprotective agent. . Another embodiment provides an effective cosmetic formulation for mimicking soft tissue at a desired site in a subject, the formulation comprising about 25% to 99% by weight of a liquid crystal forming compound, about 0% to about 75% by weight of solvent, and other compounds, as required, to provide effective viscosities and textures to limit the tissue soft. In related embodiments, the cosmetic formulation may additionally comprise an antioxidant, and the antioxidant may be a water-soluble or oil-soluble antioxidant, including any of vitamin C, sodium bisulfate, sodium sulfite, sodium metabisulfite, cysteine hydrochloride, thioglycolic acid, sulfur dioxide, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, lecithin, propyl gallate, vitamin D or any combination thereof. The embodiments of the invention also provide that any of the described formulations may additionally comprise an enhancing or therapeutic agent, including a hemostat.; a coagulation enhancing agent; a vasoactive agent; a tissue growth stimulant; a promoter of healing; an anti-infection agent, an adhesion enhancer; an agent that can swell; a thickening agent; an anesthetic; a solvent; a co-solvent; a thinning agent; a filler; an anti-scar formation agent, an anti-inflammatory agent; a physiologically compatible monovalent ion, divalent ion, trivalent ion and salt thereof; a bleaching agent including a tooth whitening agent, a peroxide; a miscellaneous medication; a controlled release enhancing material; an embolic enhancing material; or any combination thereof. In addition, in any described formulation, the enhancing agent or medicament can be suspended or dissolved in the formulation, the component for controlled release administration can be a biodegradable polymer, the enhancer that can swell can be a starch, a natural gum, a cellulosic polymer, a pyrrolidone polymer, a polyacrylic acid or a combination thereof. In addition, any described formulation may be a liquid, gel or semisolid, may form a cubic phase before or after the application, and the liquid crystal forming compound may be hydrophobic and / or amphiphilic, and any preferably described formulation is biocompatible and / or biodegradable. In particular embodiments of a formulation, the enhancing or therapeutic agent can be any of a hemostat and coagulation enhancing agent including catecholamines such as epinephrine, a phospholipid, gelatin, collagen, chitosan, glucosamines such as n-acetylglucosamine, an enzyme, a enzyme inhibitor, a fatty acid, a hormone, a silicone compound, bentonite, fuming silica, colloidal silica, micronized silica, diatomaceous earth, talc, titanium dioxide, potassium sulfate, aluminum sulfate, aluminum chloride, chloride ammonium, ferric sulfate, sub-ferric sulfate, copper sulfate, an astringent, whole blood, blood plasma, a blood product such as (a) platelets (b) prothrombin (c) thrombin (d) fibrin (e) fibrinogen (f) thromboplastin (g) a coagulation factor, an exothermic compound such as (a) calcium bromide (b) calcium oxide (c) calcium chloride; or a vasoactive agent including a vasoconstrictor, a cholinomimetic agent, an anticholinergic agent, a cholinergic blocker, a sympathomimetic, an anti-adrenergic agent, an adrenergic blocker, an immunogenic agent, a hormone such as vasopressin, an astringent, blood plasma, a blood product such as (a) platelets (b) prothrombin (c) thrombin (d) fibrin (e) fibrinogen (f) thromboplastin (g) a coagulation factor, an enzyme, an enzyme inhibitor; or a tissue growth and healing stimulant including gelatin, collagen, whole blood, blood plasma, a blood product such as (a) platelets (b) prothrombin (c) thrombin (d) fibrin (e) fibrinogen (f) thromboplastin (g) a coagulation factor, insulin-like growth factor, vascular endothelial growth factor, a hormone, hydroxyapatite, platelet growth factor, an enzyme, an enzyme inhibitor, stem cells, hormones, thrombin inhibitors, pepsin; or an anti-infective including tea tree oil, peroxide, by antibiotic such as ampicillin, a fatty acid, an antifungal, an antiviral, an immunogenic agent; or an adhesion enhancer including a natural polymer, a synthetic polymer, a cellulosic polymer, a carboxymethylcellulose, a polyethylene glycol or a PEG derivative, a polybutylene terephthalate or PBT derivative, a polyethylene oxide or PEO derivative, a polyacrylic acid, a polymethyl vinyl ether / maleic anhydride copolymer, a polymethyl vinyl ether / maleic acid copolymer, a polyvinyl methyl ether maleate, a polyethylene oxide, a cationic polyacrylamide polymer, an alginic acid derivative, chitosan, a glucosamine such as n-acetylglucosamine, a natural or synthetic protein, gluten, gelatin, collagen, ampicillin, a gum, gum, a cellulose gum, a phospholipid, a fatty acid, bentonite, fuming silica, colloidal silica, micronized silica, diatomaceous earth, talcum, titanium dioxide; or a swelling agent including a swellable natural or synthetic polymer, gum, a cellulose gum, an alginic acid derivative, gelatin, chitosan, a glucosamine such as n-acetylglucosamine; or a thickening agent including a natural polymer, a synthetic polymer, a cellulosic polymer, carboxymethylcellulose, a polyethylene glycol or PEG derivative, a polybutylene terephthalate or PBT derivative, a polyethylene oxide or PEO derivative, a polymethyl vinyl ether / anhydride copolymer maleic, a polymethyl vinyl ether / maleic acid copolymer, a polyvinyl methyl ether maleate, a polyethylene oxide, a cationic polyacrylamide polymer, an alginic acid derivative, chitosan, a glucosamine such as n-acetylglucosamine, a natural or synthetic protein, gluten, gelatin, collagen, ampicillin, a gum, gum, a cellulose gum, a phospholipid, a fatty acid, a multiparticulate, a multiparticulate poly (lactic-co-glycolide) PLGA, bentonite, fuming silica , colloidal silica, micronized silica, diatomaceous earth, talc, titanium dioxide, an oily oil base, an absorbent ointment base, a base of ointment in emulsion; or an anesthetic including clove-eugenol oil, tea tree oil, benzocaine, lidocaine, dibucaine, pramoxine, dyclonine; or a solvent and / or co-solvent including dodecane, peroxide, phospholipids, a fatty acid, a polyethylene glycol or PEG derivative, a polyethylene oxide or PEO derivative, a polybutylene terephthalate or PBT derivative, whole blood, blood plasma; or a thinning agent including a natural or synthetic polymer, a polar or non-polar solvent, ethanol, dodecane, a phospholipid, a fatty acid, a polyethylene glycol or a PEG derivative, an exothermic compound such as (a) calcium bromide (b) oxide calcium (c) calcium chloride; or a filler including a hyururonic acid, a fatty acid, a polyethylene glycol or PEG derivative, a polyethylene oxide or PEO derivative, collagen, whole blood, blood plasma, a blood product; or an anti-scar formation / anti-inflammatory / healing promoter including an onion extract, a UV-blocker, a spheroid, a non-steroidal anti-inflammatory drug, an oily-based ointment base, an absorbent ointment base, an ointment base in emulsion, an enzyme, an enzyme inhibitor, a tissue growth inhibitor; or a physiologically compatible monovalent, divalent or trivalent ion and salts thereof including a calcium derivative, a potassium derivative, a sulfate derivative, a chloride derivative, a fluoride derivative, potassium aluminum sulfate, aluminum chloride, ammonium chloride, ferric sulfate, sub-ferric sulfate, copper sulfate; or a bleaching agent including a tooth bleaching agent, a peroxide; or a miscellaneous drug including botulinum toxin; or a controlled release enhancing material including a multiparticulate, a multiparticulate containing a medicament, a poly (lactic-co-glycolide) multiparticulate (PLGA); or an embolic enhancer material including a multiparticle, a multiparticle containing a medicament, a poly (lactic-co-glycolide) multiparticulate (PLGA); or any combination thereof. Other embodiments provide a method for effectively controlling the biological fluid at a desired site in a subject, the method comprising administering an effective amount of a therapeutic formulation at the site comprising about 25% to 100% by weight of the crystal forming compound. liquid and about 0% to about 75% by weight of solvent for an effective period of time to control the biological fluid at the desired site. In a related embodiment, a method is provided for effectively controlling the biological fluid at a desired site in a subject, the method comprising administering an effective amount of any formulation as described above, for an effective period of time to control the fluid biological at the desired site. In such modalities, the methods can effectively control additionally the biological fluid by promoting hemostasis at the desired sited M. ; promote coagulation at the desired site; facilitate healing by inducing local effects at the desired site; and / or maintaining moisture at the desired site, particularly when the desired site is a burn. Yet another embodiment provides a method for effectively controlling the biological fluid at a desired site in a subject by providing any formulation as described above, the formulation comprising tissue filling and having increased the residence time at or near the desired site, such as way that the formulation resists elimination by the body. In related embodiments, which provides an increased residence time which additionally comprises the administration of a liquid crystal formulation, thus decreasing migration into and surrounding the desired site so that the residence time at the site is increased. In such methods, the tissue filler may be a dermal filler, bone filler, brain filler, synovial filler or muscle filler; The dermal filler can be used for lip augmentation or to adjust the apparent tonicity of the skin or attenuate the appearance of wrinkles; The synovial filler can be used as a means of synovial fluid replacement; and the tissue filler can be injected via needle access to the site. Even another embodiment provides a method for effectively controlling the biological fluid at a desired site in a subject by providing any formulation as described above wherein effective control of the biological fluid additionally comprises the formulation of a protective sealant at the desired site, so that the flow and exchange of the biological fluid is controlled and the sealing of the tissue is promoted via the formulation of the protective seal at the site. In related embodiments, the formulation can provide a healing matrix for tissue re-growth; the tissue may be a site of epithelial, connective, skeletal, glandular, muscular or nervous tissue of the subject; and the desired site may be bone tissue, dural tissue, vascular tissue, spinal tissue, or liver tissue. Another particular embodiment provides a method for effectively controlling the biological fluid at a desired site in a subject by providing any formulation as described above, wherein the biological fluid is effectively controlled which additionally comprises delaying the formation of a surgical adhesion, so that the formation of unwanted scar tissue that may result in the post-operative period in or adjacent to a surgical site is inhibited. In related embodiments, the delay in forming a surgical adhesion further comprises administering the formulation in such a way that it covers the internal tissue and prevents intimate contact and exchange of body fluid containing physiological stimulants for scar formation in the site, thus delaying the development of any adhesion of the surgical tissue. In more particular embodiments, the formulation forms a liquid crystal system, thereby decreasing migration in or on body tissues and attenuating the removal of the formulation from the site of application via the adhesion, viscosity and cohesion of the liquid crystal system formed; the administration may further comprise administering a formulation containing a scar tissue growth inhibitor to further delay the formation of an internal adhesion of surgical scar tissue; and the scar tissue growth inhibitor may be an antineoplastic agent, an anti-inflammatory agent, an antibiotic agent or a combination thereof. In even other related embodiments, the surgical site or area can be treated with the spray coating, hot melt coating, direct transfer, manual application or a combination thereof.; the body fluid can be any of blood, urine, saliva, serous fluid, synovial fluid, gastric secretions, cerebrospinal fluid, sweat, tears, bile, vitreous humor, chyme, mucus, lymph or wound exudates; and the desired site may be part of the gynecological region of the female, including the vagina, uterus or cervix. In any of the described methods for effectively controlling the biological fluid at a desired site in a subject, effective control of the biological fluid may further comprise the induction of local effects at the desired site so as to facilitate healing; the administration of a formulation containing an enhancing agent or medicament, or a combination thereof; the site may be an acute trauma wound or a chronic wound where the acute trauma wound may be an abrasion, a burn, a laceration, a puncture or an incision and where the chronic wound may be a leg ulcer, decubitus, fungal, diabetic, gastric, foot, sacral or indolent ulcer. In related embodiments, effective control may further comprise administration of the formulation to the large intestine, rectum or anal cavity by the application of an ointment, gel, enema or suppository; filling a tissue void created by trauma, illness or a surgical procedure; administration of the formulation in a molten state; administration of the formulation by continuous or intermittent positive pressure administration; and / or administration of the formulation to the site by laparoscopy, irrigation, continuous spraying, intermittent spraying, direct current, intermittent current, washing, shower, enema, implant, deposition, direct manual administration or by incorporation into a medical article. In embodiments that administer the formulation by incorporation into a medical article, the medical article may be a wound dressing, a sponge, an article for the nose, an adhesive bandage, a wound protective material, a protective material for internal vascular closure , a bandage for external vascular closure, an absorbent article that can be inflated, a fibrotic wound protective material or an article for feminine hygiene. In related embodiments, the administration may further comprise administration by means of shower, suppository, enema, irrigation, spraying, current, manual application, washing, or impregnation of a medical article, where direct manual administration may be by direct hand transfer or by a hand-controlled instrument and where the indirect manual application can be by using a vehicle for or a device impregnated with the formulation, to assist in transferring the formulation to the formulation site, wherein the transfer comprises manual rubbing, greasing or maintenance of the formulation on and / or at a tissue site. In another particular embodiment, a method for controlling blood loss at a site in a subject is provided, the method comprising administering a formulation of the thrombin inhibitor as described above at a site of blood loss in a subject, in where the formulation facilitates the coagulation of the blood, thus controlling the blood loss at the site. In related modalities, the blood loss is either menstrual discharge, post-partum bleeding, bleeding from the reproductive tract or is any body blood or exudate discharge containing water and the blood loss can be internal or external. In such embodiments, the administration may additionally comprise filling a tissue void created by a trauma, disease or a surgical procedure; administration by continuous or intermittent positive pressure administration; administration of the formulation in a molten state; or administration to the site by laparoscopy, irrigation, continuous spraying, intermittent spraying, direct current, intermittent current, washing, shower, enema, implant, deposition, direct manual application or by incorporation into a medical article. In particular related embodiments, the medical article may be any of a wound dressing, a sponge, an article for the nose, an adhesive bandage, a wound protective material, a protective material for internal vascular closure, a bandage for external vascular closure , an absorbent article that can be inflated, a fibrotic wound protective material or an article for feminine hygiene. Even other particular embodiments provide a method for administering any therapeutic formulation as described above, the method comprising administering the formulation directly to an arterial vein or tissue at a vascular access site in a subject; administering the formulation so that it contacts the tissue adjacent to a vascular access site in a subject; administration by retro-filling an access tract with the formulation from the vascular access site to the epidermis; administration of the formulation to the superficial tissue of a vein or arterial access site; and / or use of an implant article for administration that has been impregnated with the formulation. In such embodiments, the article may comprise collagen, gelatin, chitosan, chitin, poly (lactic-co-glycolide) (PLGA), poly n-acetylglucosamine or a combination thereof; and the administration may further comprise the application of the therapeutic formulation during or immediately after removal of a needle, cover or access catheter from the access site.

Another particular embodiment provides a method for administering any therapeutic formulation as described above to a desired tissue site in a subject, the method comprising administering the formulation to the desired tissue site to carry out the tissue sealing, wherein the tissue is selected from the group consisting of epithelial, connective, skeletal, glandular, muscular and neural tissue. In related embodiments, the administration may further comprise administration to neural tissue to inhibit the progression of paralysis, wherein the formulation comprises cerebrospinal fluid as a solvent, and wherein the cerebrospinal fluid is obtained from the subject. Other related embodiments may further comprise administering the formulation to a bone tissue site to seal an opening, thereby inhibiting the loss of body fluid and providing a protective barrier in the opening, wherein the formulation comprises whole blood, platelets, rich plasma in platelets, or plasma as a solvent, wherein the whole blood or platelets, platelet-rich plasma, or plasma is obtained from the subject, and wherein the administration further comprises promoting re-growth of the bone. In more particular related embodiments, a method is provided for the administration of any therapeutic formulation as described above to a desired tissue site in a subject to carry out tissue sealing, wherein the tissue seal may additionally comprise filling of a tissue vacuum created by a trauma, illness or a surgical procedure; the administration may further comprise administration at continuous or intermittent positive pressure; administration of the formulation in a molten state; and / or administration to the site by laparoscopy, irrigation, continuous spraying, intermittent spraying, direct current, intermittent current, washing, shower, enema, implant, deposition, direct manual applications or by incorporation into a medical article. In such embodiments, the medical article can be any of a wound dressing, a sponge, an article for the nose, an adhesive bandage, a wound protective material, a protective material for internal vascular closure, a bandage for external vascular closure, an absorbent article that can be inflated, a fibrotic wound protective material or an article for feminine hygiene. Even another particular embodiment provides a method for facilitating effective closure of a vascular wound or incision site at a desired site in a subject, the method comprising administration, optionally by positive pressure, an effective amount of a biodegradable therapeutic formulation compatible in the site of the vascular wound or incision site, the formulation comprising about 25% to 100% by weight of a compound that forms liquid crystal and about 0% to about 75% by weight of solvent, wherein the formulation affects hemostasis by staking Physically the blood flow, absorb fluid, and induce local effects at the site within approximately 10 minutes or less after on-site administration, thus facilitating effective closure of the vascular wound or incision. In particular related embodiments, the formulation physically stirs the blood flow, absorbs fluids, and induces local effects within about 5 minutes or less, more particularly within about 1 minute or less, and even more particularly within about 30 seconds or more. less. Even another particular embodiment provides a method for administering any formulation as described above to a desired site in a subject, the method comprising administering the formulation to the desired site by injection, more particularly, administration of the formulation by direct injection into the circulatory system of the subject, even more particularly injection via an access device such as a wire guided catheter, and even more particularly by injecting and administering the formulation for embolization therapy. In such modalities, embolization therapy is the treatment of tumors, or the treatment of bleeding. Another particular embodiment provides a method for inhibiting tissue adhesion to a medical article, the method comprising coating said medical article with any formulation as described above, thereby inhibiting tissue adhesion to said article and reducing pain and trauma. after the application and the subsequent removal of the medical article. In particular related embodiments, the medical article is a wound dressing, a burn dressing, fibrotic protective material, an adhesive bandage, a hemostatic article for nasal bleeds, a medical article that can be implanted or medical hardware that is intended for a subject human or veterinary. Even another particular embodiment provides a method for sterilizing any previously described formulation or device containing said formulation, the method comprising sterilization by filtration, distillation, thermal exposure, exposure to ionizing radiation, aseptic processing, steam heating under pressure, pressure heating , or exposure to a gas the formulation or device that contains the formulation before use. Another particular modality provides a hemostatic emergency kit for performing hemostasis at a bleeding site in a subject within approximately 15 minutes or less, the equipment comprising any sterile formulation as described above, and the means for the application of the formulation to the bleeding site. In a more particular related embodiment, the means for application of the formulation is either a positive pressure irrigation device, a swab, a spray applicator, a syringe, an eye dropper, a wound dressing, an adhesive bandage, a pressure element, a pipette, an enema, a suppository, a sealed container for direct application to the bleeding site after its opening, or any other suitable means for application of said formulation.

In other related embodiments, the equipment may be prepared for other treatment methods, such as methods for controlling body fluid, promoting healing, treating a burn, bandaging a wound, sealing the tissue, as described above. , said equipment provides appropriate sterile formulations and means for the application of said formulations. The related embodiments may additionally comprise articles for wound dressing, such as bandages, gauze, plugs, sutures, cleaning materials, all treated with or containing sterile formulations for the required treatment, the equipment being easily assembled for use in containers. . Another particular embodiment provides a method for effectively mimicking soft body tissues at a desired site in a subject, the method comprising administering an effective amount of a cosmetic formulation as previously described internally at the desired site. In related embodiments, the formulation is either a liquid, a gel or a semi-solid; the formulation can be adapted for use as a filling means for a cosmetic and reconstructive implant device; the formulation can form a cubic phase after filling the device; The formulation can form a cubic phase before filling the device. In other related embodiments, the device for implant is a breast implant, an implant for vacuum tissue, a gluteal implant, a facial implant or a chest implant; the filling means of the formulation can be increased, decreased or exchanged via an access site to the implant where the implant is placed just below the skin of a subject; the device for implant can be constructed of a plurality of compartments to maintain the medium wherein the compartments allow movement of the medium between the compartments and where the compartments are connected by an opening, the size of which affects the average movement speed between the compartments; the device for implant is constructed from a plurality of compartments to maintain the medium wherein the compartments do not allow movement of the medium between the compartments; or the plurality of compartments has a wedge shape, each compartment expanding from a central point where the compartments are centrally located, as in the pie chart.

BRIEF DESCRIPTION OF THE DRAWINGS The foregoing features of the invention will be more readily understood with reference to the following detailed description, taken with reference to the accompanying drawings, in which: Figure 1 is a photograph showing the three physical states of a hemostatic composition in accordance with the present invention, wherein the physical state is a liquid, a more viscous liquid or a firm semi-solid, respectively, from left to right.

Figures 2A, 2B and 2C show a series of photographs depicting a hemostatic composition in accordance with the present invention as a low viscosity liquid that can be sprayed, a viscous gel that can be extruded from a syringe, or a semi -solid solid, respectively, from left to right. Figures 3A and 3B show a hemostatic agent of the prior art being applied to a tail amputation site of a rat (Figure 3A) and the inability to control bleeding (Figure 3B). Figures 4A and 4B show a hemostatic agent in accordance with the present invention that is applied to a tail amputation site of a rat resulting in immediate post-irrigation hemostasis (Figure 4A) and total control of bleeding (Figure 4B) ). Figures 5A and 5B show the application of a hemostatic agent according to the present invention to a laceration of the saphenous vein of a rat (Figure 5A) followed by post-irrigation hemostasis and control of bleeding (Figure 5B). Figures 6A and 6B show the application by pulse current pulse of a hemostatic agent according to the present invention seconds after a lesion by exsanguination (in 50% and 25% excision of hepatic lobes of the rat) to a liver lobe of pig (figure 6A) followed by immediate hemostasis post-irrigation and total control of bleeding.

Figures 7A and 7B show the application of a hemostatic agent using a non-optimal spill technique according to the present invention seconds after a 10 minute exsanguination injury (2 cm incision) to a pig liver (Figure 7A) followed by immediate hemostasis post-irrigation and control of bleeding, despite the limited technical application (Figure 7B). Figures 8A and 8B show the application of a pulse of pressurized current of a hemostatic agent according to the present invention seconds after the injury by exsanguination to a pig liver lobe (Figure 8A), compared to the application of a hemostatic agent according to the present invention seconds after a lesion by exsanguination to a pig liver lobe using non-optimal effusion (Figure 8B). Figures 9A and 9B show the application of a hemostatic agent using a positive pulse pressure current technique in accordance with the present invention in a 5 minute exsanguination lesion (3 cm incision) to a pig liver lobe (FIG. 9A) followed by post-irrigation hemostasis, hemorrhage control using gauze treated with a hemostatic formulation in accordance with the present invention, and cleansing for immediate control of bleeding (Figure 9B). Figures 10A to 10E show the application of a hemostatic agent in accordance with the present invention applied to a dog bite on a human thumb (Figure 10A) followed by post-irrigation hemostasis and control of bleeding (Figure 10B), continuous hemostasis after 12 hours (Figure 10C) and minimal tissue disfigurement and scar formation at the site of the lesion (Figures 10D and 10E). Figures 1 1 A to 1 1 D show scanning electron microscopy (SEM) images at 2 seconds (figure 1 1 A), 1 minute (figure 1 B), 5 minutes (figure 1 C) and 10 minutes (figure 1 1 D) after the application of a hemostatic agent in accordance with the present invention to a site of bleeding in a subject. As can be seen in Figure 1A, the platelets had already aligned non-randomly at the site at two seconds, larger numbers of platelets congregate at the site at one minute (Figure 1 1 B), evidence Tertiary coagulation / healing is evident after 5 minutes (figure 11 C), and continuous coagulation / healing is evident at 10 minutes after application (figure 1 D). Figures 12A and 12B show a hemostatic formulation according to the present invention comprising glyceryl monooleate and whole blood in the crystalline liquid cubic phase, where deformed total erythrocytes bound to the liquid crystal GMO formulation have been observed, as well as a platelet activated and a thin fibrin mesh at 20 seconds (FIG. 12A) and an approach of an activated platelet unit to the formulation (FIG. 12B).

DETAILED DESCRIPTION OF THE SPECIFIC MODALITIES Definitions As used in this description and the appended claims, the following terms should have the meanings indicated, unless the context otherwise requires: "Liquid crystal" as used in the present invention, means any substance having as one of its physical states a liquid crystalline state. Liquid crystals are typically organic molecules of moderate size, but they can also be large (for example polymers) which tend to be elongated and oblong, although a variety of other forms are also possible. Due to their elongated shape, under appropriate conditions the molecules can exhibit an orientation order, in such a way that all the axes are aligned in a particular direction. Consequently, the general order has profound influences on the physicochemical properties of the material, and the way in which the material acts. For example, if the direction of the orientation varies in the species, the orientation of the light (for example, the polarization) can follow this variation. A well-known application of this phenomenon is in the ubiquitous liquid crystal display. Under other conditions the molecules can form a stack of layers along one direction, but they remain liquid-like (in terms of the absence of the translation order) within the layers. As the system changes from one of these phases to another, a variety of physical parameters such as susceptibility and thermal capacity, will exhibit "pretransitional behavior." Based solely on symmetry, this behavior can be related to other physical systems, such as superconductivity, magnetism, or superfluidity; this is the so-called "universality" of these phase transitions. As used in the present invention, "liquid crystal" also comprises a large class of highly anisometric molecules (as opposed to ordinary fluids that are isotropic in nature and appear optically, magnetically, electrically, etc. as the same from any perspective) which results in macroscopic anisotropic behavior, which results in unusual, fascinating, and potentially technologically and biologically relevant behavior. Examples of such molecules include polymers, micelles, microemulsions, and materials of biological importance, such as fatty acids, DNA and membranes. As used in the present invention, a described formulation comprising a liquid crystal forming compound can be a liquid, gel or semi-solid, steppe forming a cubic phase before or after application, and the liquid crystal forming compound can be hydrophobic and / or amphiphilic. In addition, the described formulations comprising a liquid crystal forming compound are preferably biocompatible and / or biodegradable. "Glyceryl monooleate" as used in the present invention, comprises glycerol monooleate, both are used interchangeably to represent the same monoester formed between the reaction of oleic acid with glycerol. Accordingly, as used in the present invention, "GMO" is established for glyceryl monooleate or glycerol monooleate, wherein both are one and the same compound. For all formulations, the exact percentage of the liquid crystal forming compound, particularly glyceryl monooleate, can vary, depending on the source or supplier of the compound, because all commercially available reagents are not identical, since exact levels of purity can to vary. For example, a commercial source for GMO lists the purity as not less than 80% glyceryl monooleate. "Positive pressure" as used in the present invention, means the use of a force to create pressure greater than that which could exist by means of a system of atmospheric, gravitational or biological force alone, either through a spray device or pump , manually applied physical pressure, directly or indirectly, application of force through a manual or automated use of a device. The phrase, used in conjunction with the application, as in "positive pressure application" includes the application of a formulation as described in the present invention, or a device comprising a formulation as described in the present invention, by use of a positive pressure irrigation device such as a swab, a spray applicator, a syringe, an eye dropper, a wound dressing, an adhesive bandage, a pressure element, a pipette, an enema, a suppository, a container sealed for direct application to the bleeding site after opening, or any other means suitable for the application of the formulation in conjunction with the use of indirect or direct force. For example, in a wound to a vein or artery, where the blood loss is exacerbated by pumping the heart, the positive pressure means uses the force at the site to apply a described formulation, or the device is comprised of said formulation, to a greater degree than the force from the heart that contributes to the loss of blood. Other positive pressure examples include the use of the force generated by the spraying or application of a current pulse of a described formulation to a desired site, such as a burn, such that the formulation is directed, using a force greater than gravity, to the desired site. A particular embodiment of the invention provides a method for producing a liquid crystalline formulation capable of being formulated in the form of fluid and non-fluid with variable viscosity wherein the forms can be applied to the site of injury or a tissue alteration in humans or animals to decrease or stop the loss of blood or body fluids. The method may comprise producing the liquid crystalline formulation by hydration or solvation of a precursor material a liquid crystalline form, for example, glyceryl monooleate (GMO). The liquid crystalline formulation of glyceryl monooleate is produced by heating the melting material with the addition of an aqueous solvent system. A particular example of an aqueous solvent system suitable for addition to the crystalline precursor material is sodium chloride solution (saline). An example of a liquid crystalline formulation formulated as a fluid or in a liquid state is a GMO-based formulation comprising about 5% w / w saline (final concentration of NaCl about 0.045%, by weight), thus producing a formulation with a viscosity in the range of about 80-300 centipoise. An example of a liquid crystalline formulation that can be formulated as a fluid semi-solid could be a GMO-based formulation comprising about 10% saline, thereby producing a formulation with a viscosity in the range of about 1000-5000 centipoise. A further example of a liquid crystalline formulation that is formulated as a non-fluid formulation could be a GMO-based formulation comprising about 30% saline, thereby producing a formulation with an excess viscosity of about 1, 200,000 centipoise. An example of an application method includes pressurized irrigation as achieved through a syringe or other similar device. Another embodiment of the invention is a method for the production of a liquid crystalline formulation capable of being formulated in a fluid or non-fluid form of variable viscosity that can be applied to the site of injury or alteration of tissue in humans or animals to slow down or stopping the loss of blood or bodily fluids, the method comprising: producing the liquid crystalline formulation by hydration or solvating the liquid crystalline precursor material. An example of a liquid crystalline precursor material is glyceryl monooleate (GMO). The liquid crystalline formulation of glyceryl monooleate is produced by heating the material to melt with the addition of a non-aqueous solvent formulation. An example of a non-aqueous solvent system is isopropyl myristate. An example of a liquid crystalline formulation that is formulated as a fluid or liquid state could be a GMO-based formulation containing approximately 10% isopropyl myristate producing a formulation with a viscosity in the approximate range of 80-500 centipoise. Another embodiment of the invention is a method for the production of a liquid crystalline formulation capable of being formulated in a fluid or non-fluid form of variable viscosity that can be applied to the site of injury or tissue alteration in humans or animals to do more slow or stop the loss of blood or bodily fluids, the method comprising: producing the liquid crystalline formulation by hydration or solvating the liquid crystalline precursor material. An example of a liquid crystalline precursor material is glyceryl monooleate (GMO). The liquid crystalline formulation of glyceryl monooleate is produced by heating the material to melt with the addition of a non-aqueous, semi-polar solvent system. An example of a non-aqueous, semi-polar solvent system is polyethylene glycol 200. An example of a liquid crystalline formulation that is formulated as a fluid or liquid state could be a GMO-based formulation containing about 10% propylene glycol producing a formulation with a viscosity approximately in the range of 80-500 centipoise.

Another embodiment of the invention is a method for the production of a liquid crystalline formulation capable of being formulated in a fluid or non-fluid form of variable viscosity that can be applied to the site of injury or tissue alteration in humans or animals to do more slow or stop the loss of blood or bodily fluids, the method comprising: producing the liquid crystalline formulation by hydration or solvating the liquid crystalline precursor material. An example of a liquid crystalline precursor material is glyceryl monooleate (GMO). The liquid crystalline formulation of glyceryl monooleate is produced by heating the material to melt with the addition of a mixture of an aqueous and non-aqueous solvent system. An example of a liquid crystalline formulation that is formulated as a fluid or liquid state could be a GMO-based formulation containing about 5% saline and about 5% ethanol producing a formulation with a viscosity in the approximate range of 80-80. 500 centipoise.

Method for the production of LCS containing enhancer / therapeutic agent Another embodiment provides a pharmaceutical formulation comprising a compound that forms liquid crystal and an enhancer or therapeutic agent that can be applied to the site of injury or tissue alteration in humans or animals for slow down or stop the loss of blood or body fluids. More particularly, the formulation comprises a liquid crystalline formulation solvated or hydrated with a therapeutic agent or dissolved enhancing agent, suspended or dispersed in aqueous solvent system prior to the production of the liquid crystalline formulation. An example of an aqueous solvent system is purified water. An example of an enhancer or therapeutic agent is a soluble calcium salt such as calcium gluconate or calcium chloride. Another embodiment provides a method for the production of a liquid crystalline formulation containing enhancer / therapeutic agents that can be applied to the site of injury or tissue alteration in humans or animals to slow down or stop the loss of blood or body fluids. , the formulation comprising a liquid crystalline formulation solvated or hydrated with a therapeutic agent or agents suspended or dispersed in an aqueous solvent system prior to the production of the liquid crystalline formulation. An example of an aqueous solvent system is purified water. An example of a therapeutic agent is colloidal silicon dioxide. Another embodiment provides a method for the production of a liquid crystalline formulation containing therapeutic agents that can be applied to the site of injury or tissue alteration in humans or animals to slow down or stop the loss of blood or body fluids, the formulation comprising a liquid crystalline formulation solvated or hydrated with a therapeutic agent or agents dissolved or dispersed in an aqueous solvent system prior to the production of the liquid crystalline formulation. An example of a non-aqueous solvent system is ethanol. An example of a therapeutic agent is benzocaine. Another embodiment provides a method for the production of a liquid crystalline formulation containing therapeutic agents that can be applied to the site of injury or tissue alteration in humans or animals to slow down or stop the loss of blood or body fluids, the formulation comprising a liquid crystalline formulation solvated or hydrated with a therapeutic agent or agents suspended, dissolved or dispersed in an aqueous solvent system prior to the production of the liquid crystalline formulation. An example of a non-aqueous solvent system is cottonseed oil. An example of a therapeutic agent is potassium aluminum sulfate. Another embodiment provides a method for the production of a liquid crystalline formulation containing enhancer / therapeutic agents that can be applied to the site of injury or tissue alteration in humans or animals to slow down or stop the loss of blood or body fluids., the formulation comprising a liquid crystalline formulation solvated or hydrated with an enhancer / therapeutic agent or agents dissolved or dispersed in a liquid crystalline precursor material prior to the production of the liquid crystalline formulation. An example of a therapeutic agent / enhancer is phosphatidylserine. Another embodiment provides a method for the production of a liquid crystalline formulation containing enhancer / therapeutic agents that can be applied to the site of injury or tissue alteration in humans or animals to slow or stop the loss of blood or body fluids. , comprising a crystalline liquid formulation solvated or hydrated with an enhancer / therapeutic agent or agents suspended or dispersed in a liquid crystalline precursor material prior to the production of the liquid crystalline formulation. An example of an enhancer / therapeutic agent is collagen.

Method for the application / administration of LCS Another embodiment of the invention provides an improved method for administration to a site of injury or tissue alteration reducing the possibility of secondary contamination. The method of improved administration comprising: stream or gravity directed flow of the formulation by the container of the primary protective material.

Terminally sterile Another embodiment of the invention provides an improved method for administration to a site of injury or tissue disruption reducing the possibility of secondary contamination. The improved administration method comprising: direct pressurized aspersion or stream of the formulation by means of mechanical pressurization as in a piston or piston-type system.

Another embodiment of the invention provides an improved method for administration to a tissue injury or alteration site reducing the possibility of secondary contamination. The improved administration method comprising: direct pressurized aspersion or stream of the formulation by means of mechanical pressurization as in a container-type system for oppressing. Another embodiment of the invention provides an improved method for administration to a tissue injury or alteration site reducing the possibility of secondary contamination. The improved administration method comprising: direct pressurized aspersion or stream of the formulation by means of gaseous propellants as in an aerosol type system.

(Method of application / administration of LCS in or on secondary medical structures Another embodiment of the invention provides a method for administration to a site of injury or tissue alteration.The method of administration comprising: administration of the formulation through of its transport in or on a medical structure such as a surgical gauze Another embodiment of the invention provides a method for administration to a site of tissue injury or alteration The method of administration comprising: administration of the formulation through its transport in or on a medical structure such as a cotton-swab device Another embodiment of the invention provides a method for administration to a site of injury or tissue alteration The method of administration comprising: administration of the formulation through its transport in or on a medical structure such as a bandage prim Occlusive or non-occlusive.

Method of application / administration of LCS-vascular closure Another embodiment of the invention provides a method for the administration of the tissues surrounding the venous or arterial access site. The method of administration comprising: administering the formulation by direct injection or instillation into the access tract after removal of an access needle or catheter. Another embodiment of the invention provides a method for the administration of the tissues surrounding the venous or arterial access site. The method of administration comprising: administering the formulation by injection or instillation through a multiple lumen, balloon catheter system used for retro-filling the access tract. The catheter system is removed after the placement of the invention. Another embodiment of the invention provides a method of administration to the superficial tissues of a vein or arterial access site. The method of administration comprising: administering the formulation by direct application to the superficial access tract during or immediately after removal of an access needle or catheter. The invention can be placed on site alone or in combination with an occlusive or non-occlusive dressing or pressure bandage.

Method of application / administration of LCS-embolization therapy Another embodiment of the invention provides a method for administration to the circulatory system for embolization therapy. The method of administration comprising: administering the formulation by injection through the intravenous or intra-arterial access method such as a wire-guided catheter.

Method of application / administration of female LCS-hiqiene Another embodiment of the invention provides a method of administration to the female reproductive tract. The method of administration comprising: administration of the formulation through transport in or on catamenial products in or on the female reproductive tract such as a tampon or female towel or pad. Another embodiment of the invention provides a method for administration to the female reproductive tract. The method of administration comprising: administration of the formulation through its transport in the form of a shower.

Another embodiment of the invention provides a method of administration to the female reproductive tract. The method of administration comprising: administration of the formulation through its transport in the form of a suppository or ovule.

Method of application / administration of LCS-inferior-rectal gel Another embodiment of the invention provides a method of administration to the structures of the large intestine, rectum and anus. The method of administration comprising: administration of the formulation through its transport in the form of an enema. Another embodiment of the invention provides a method of administration to the structures of the large intestine, rectum and anus. The method of administration comprising: administration of the formulation through its transport in the form of a suppository. Another embodiment of the invention provides a method of administration to the structures of the large intestine, rectum and anus. The method of administration comprising: administering the formulation through its transport in the form of a semisolid ointment.

Lubricant Another embodiment of the invention provides a persistent lubrication method to assist in the placement or removal of a device or structure within the body. The method comprising: application of the formulation in or on a device or structure such as a surgical gauze for epistaxis or nasal protection material. The liquid crystalline formulation provides a physical, insoluble barrier between the tissue and the device or structure that easily deflects and lubricates the surfaces for insertion or removal from the application site.

Cosmetic Surgery Another embodiment of the invention provides a utility method for direct cosmetic enhancement of tissues. The method comprising: the injection of the formulation into the tissues of the body to increase the volume of the tissues to increase the aesthetic characteristics. Another embodiment of the invention provides a method of utility in implantable devices for cosmetic augmentation such as breast and gluteal implants. The method comprising: producing the formulation having the desired consistency of adipose or muscle tissue and subsequent incorporation into a polymeric or elastomeric shell for implant.

B or hardware Another embodiment of the invention provides a method of applying prosthetic implantable hardware to reduce or eliminate the formation of bacterial infections by biofilm. The method comprising: applying the formulation in or on a hardware device or structure by a spray coating method, hot melt coating or dip coating prior to or at the time of implantation. The liquid crystalline formulation provides a physical, insoluble barrier that resists the adhesion or deposition of bacteria capable of producing biofilm infections.

Wound healing Another embodiment of the invention provides a method of application to chronic wounds of soft tissues such as decubitus ulcers. The method comprising: the application of the formulation to the wound after cleaning or debridement. The liquid crystalline formulation provides a physical, insoluble barrier that resists contamination as well as maintains an advantageous moisture balance below the barrier.

Adhesions Another embodiment of the invention provides a method for reducing or eliminating the formation of surgical adhesions. The method comprises the application of the formulation near or at the site of a surgical manipulation. The liquid crystalline formulation provides a physical, insoluble barrier between manipulated tissues that reduce the propensity for hypertrophic scarring that leads to tissue adhesion.

EXAMPLE 1 Purified water, USP 5% glyceryl monooleate 95% Purified water, USP was heated to approximately 40 ° C. Glyceryl Monooleate (GMO) was heated to molten. The purified water was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 80-500 centipoise. The present example has characteristics that make it operable as a hemostatic agent, for the control of the fluid, and / or for wound healing in the formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to the superficial or internal wounds, and affected tissue. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage.

EXAMPLE 2 Saline solution for injection, USP 5% Glyceryl monooleate 95% Saline solution for injection, USP, was heated at approximately 40 ° C. Glyceryl monooleate (GMO) was heated to molten. The saline was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 80-500 centipoise. The present example has characteristics that make it operable as a hemostatic agent, for the control of the fluid, and / or for wound healing in the formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to the superficial or internal wounds, and affected tissue. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage.

EXAMPLE 3 Ethanol, 190 alcoholic strength 5% Glyceryl monooleate 95% 95% ethanol was heated to approximately 40 ° C in a closed container. Glyceryl monooleate (GMO) was heated to molten. The ethanol was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 80-500 centipoise. The present example has characteristics that make it operable as a hemostatic agent, for the control of the fluid, and / or for wound healing in the formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to the superficial or internal wounds, and affected tissue. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage.

EXAMPLE 4 Ethanol, 190% alcoholic strength 5% Saline solution for injection, USP 5% Glyceryl monooleate 90% Ethanol and saline were thoroughly mixed and heated to approximately 40 ° C in a closed container. Glyceryl monooleate (GMO) was heated to molten. The ethanol / saline mixture was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 80-500 centipoise. The present example has characteristics that make it operable as a hemostatic agent, for the control of the fluid, and / or for wound healing in the formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to the superficial or internal wounds, and affected tissue. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage.

EXAMPLE 5 Propylene glycol, USP 5% Glyceryl monooleate 95% Propylene glycol, USP, was heated at about 40 ° C. Glyceryl Monooleate (GMO) was heated to molten. The propylene glycol was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a light colored liquid formulation with a viscosity in the approximate range of 80-200 centipoise. The present example has characteristics that make it operate as a hemostatic agent, for fluid control, and / or for wound healing in the formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to the superficial or internal wounds, and affected tissue. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage.

EXAMPLE 6 Cottonseed oil, NF 20% Glyceryl monooleate 80% Cottonseed oil, NF, was heated at about 40 ° C. Glyceryl monooleate (GMO) was heated to molten. The cottonseed oil was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a light colored liquid formulation with a viscosity in the approximate range of 80-200 centipoise. The present example has characteristics that make it operable as a hemostatic agent, for the control of the fluid, and / or for wound healing in the formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to the superficial or internal wounds, and affected tissue. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage. The use of the non-polar solvent in the present example offered the ability to alter the rate of conversion to the final liquid crystalline state as well as the character of the system. In this case, the conversion speed was reduced to a process that required 2-5 minutes to finish with a reduction in the viscosity of the terminal state.

EXAMPLE 7 Phosphatidylserine 20% powder 10% Saline for injection, USP 5% Glyceryl monooleate 85% Phosphatidylserine 20% (PS) powder was dispersed and hydrated with saline for injection, USP. Glyceryl monooleate (GMO) was heated to molten. The PS mixture was combined with GMO and mixed well. The resulting mixture produced a yellowish-brown gel formulation with a viscosity in the approximate range of 800-2000 centipoise. The present example possesses features that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue in cases where precision is desired. of the application and the reduction in the potential migration of the system in the area or to the surrounding tissues. The addition of phosphatidylserine serves an adjunct role as a potential mediator in the normal coagulation cascade.

EXAMPLE 8 Phosphatidylserine 20% powder 10% Saline for injection, USP 5% Glyceryl monooleate 85% slow glyceryl monooleate (GMO) until molten. Phosphatidylserine 20% (PS) powder was dispersed in the molten GMO. The molten mixture was then hydrated with saline for injection, USP, with mixing. The PS mixture was combined with GMO and mixed well. The resulting mixture produced a brownish-brown liquid formulation with a viscosity in the approximate range of 60-200 centipoise. The present example has characteristics that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue. The addition of phosphatidylserine serves an adjunct role as a potential mediator in the normal coagulation cascade.

EXAMPLE 9 Ampicillin 250 mg powder for injection Glyceryl monooleate Glyceryl monooleate (GMO) was heated to melt. Ampicillin 250 mg powder for reconstitution was dispersed in the molten GMO. The resulting mixture produced an adhesive, elastic mass with high viscosity. The present example produced an adhesive elastic formulation operable as a therapeutic bandage system for insertion into and adhesion to wounds as produced by venous stasis and diabetic ulcers in the foot. The formulation facilitates healing and can be used to prevent or treat secondary bacterial infections that often accompany these conditions. The formulation can also be used in articles for wound dressing for the treatment of variable degree burns, to control infection, fluid control (exudation) and protect the burn surface from abrasion and re-injury / loss of tissue after of bandage change.

EXAMPLE 10 Potassium chloride solution 1 meq / mL 10% Glyceryl monooleate 90% Concentrated potassium chloride (KCI) 2 meq / ml was diluted to a concentration of 1 meq / ml using water for injection, USP. This dilution was heated to about 40 ° C. Glyceryl monooleate (GMO) was heated to molten. The KCI solution was combined with GMO and mixed well. The resulting mixture produced a clear solid formulation with a viscosity in the approximate range in excess of 1.2 million centipoise.

EXAMPLE 11 Potassium chloride solution 1 meq / mL 5% Glyceryl monooleate 95% Potassium chloride (KCI) 2 meq / ml was diluted to a concentration of 1 meq / ml using water for injection, USP. This dilution was heated to about 40 ° C. Glyceryl monooleate (GMO) was heated to molten. The KCI solution was combined with GMO and mixed well. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 80-200 centipoise. The present example has characteristics that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue.

EXAMPLE 12 Cholesterol, USP 10% Saline for injection, USP 5% Glyceryl monooleate 85% Glyceryl monooleate (GMO) was heated until molten. Cholesterol, USP powder was dispersed in the molten GMO. The molten mixture was then hydrated with saline for injection, USP with mixing. The resulting mixture produced a white liquid formulation with a viscosity in the approximate range of 60-200 centipoise. The present example possesses characteristics that make it operable as a hemostatic agent or as an agent for wound healing in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue. The addition of cholesterol serves to decrease the conversion rate as well as the consistency of the terminal phase.

EXAMPLE 13 Crospovidone, NF 10% Saline for injection, USP 5% Glyceryl monooleate 85% Glyceryl monooleate (GMO) was heated until molten. The crospovidone, NF powder was dispersed in the molten GMO. The molten mixture was then hydrated with saline for injection, USP with mixing. The resulting mixture produced a firm, white gel formulation with a viscosity in the approximate range of 10,000-30,000 centipoise. The present example possesses features that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue, in cases where the precision of application and reduction in the potential migration of the system in the area or to the surrounding tissues. The addition of crospovidone serves an adjunct role as a swelling agent that is capable of absorbing blood or body fluids and subsequently controllably inflated to additionally apply secondary physical pressure to the treated area.

EXAMPLE 14 Crospovidone, NF 10% Saline for injection, USP 5% Glyceryl monooleate 85% Glyceryl Monooleate (GMO) was heated until molten. Povidone K29 / 32, NF powder was dispersed in the molten GMO. The molten mixture was then hydrated with saline for injection, USP with mixing. The resulting mixture produced a thick, opaque, silky gel formulation with a viscosity in the approximate 2000-5000 centipoise range.

The present example possesses features that make it operable as a hemostatic or therapeutic wound care agent in formulations for administration to superficial or internal wounds and affected tissue by means of washing or irrigation, as well as by presumed methods of administration, in the cases where the precision of application and reduction in the potential migration of the agent in the area or nearby tissues is desired. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage. The addition of crospovidone serves an adjunct role as an agent to increase tissue adhesion.

EXAMPLE 15 Pemulen® TR2 1% Saline for injection, USP 5% Glyceryl monooleate 85% Glyceryl Monooleate (GMO) was heated to a melt. Pemulen® TR2, NF powder was dispersed in the molten GMO. The molten mixture was then hydrated with saline for injection, USP with mixing. The resulting mixture produced an elastic, adhesive gel formulation with a viscosity in the approximate 100,000-300,000 centipoise range. It is understood that other methacrylic acid copolymers and derivatives thereof can be exchanged for Pemulen® TR2 in the present example. The present example possesses features that make it operable as a hemostatic or therapeutic wound care agent in formulations for administration to superficial or internal wounds and affected tissue by means of washing or irrigation, as well as by means of pressurized methods of administration, in cases where the precision of application and reduction in the potential migration of the agent in the area or nearby tissues is desired.

EXAMPLE 16 Polyethylene glycol (PEG) 400, NF 10% Polyethylene glycol (PEG 200, NF 5% Glyceryl monooleate 85% PEG 400, NF and PEG 200, NF were mixed and heated to about 40 ° C. Glyceryl monooleate (GMO) was heated to molten. The PEG mixture was combined with GMO.The resulting system was mixed well and allowed to return to room temperature without disturbance.The resulting mixture produced a light colored liquid formulation with a viscosity in the approximate range of 80-200 centipoise. Alternatively, other PM's of PEGs may also be useful, and are exchanged with those previously described to produce alternative formulations having similar properties making said formulations operable as hemostatic agents.The present example possesses characteristics that make it operable as a hemostatic agent, for control of the fluid, and / or for wound healing in the formulations for administration by means of washing or irrigating tion, as well as by pressurized methods of administration, to superficial or internal wounds, and affected tissue. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage.

EXAMPLE 17 Isopropyl myristate, NF 5% Glyceryl monooleate 95% Isopropyl myristate, NF, (IPM) was heated to approximately 40 ° C. Glyceryl monooleate (GMO) was heated to molten. The IPM was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a hazy gel formulation with a viscosity in the approximate range of 800-3000 centipoise. The present example possesses features that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue, in cases where the precision of application and reduction in the potential migration of the system in the area or to the surrounding tissues.

EXAMPLE 18 Solution of 10% calcium gluconate 5% Glyceryl monooleate 95% The calcium gluconate solution was heated to approximately 40 ° C. Glyceryl monooleate (GMO) was heated to molten. Calcium gluconate was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 80-200 centipoise. The present example has characteristics that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue. The addition of calcium ions served an adjunct role as a physiological mediator to supplement the normal coagulation cascade. EXAMPLE 19 Sodium hyaluronate 2.5% Saline for injection, USP 5% Glyceryl monooleate 92.5% Sodium hyaluronate was dissolved in the saline solution and heated to approximately 35 ° C. Glyceryl monooleate (GMO) was heated to molten. The sodium hyaluronate solution was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a hazy liquid formulation with a viscosity in the approximate range of 1000-3000 centipoise. The present example has characteristics that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue in cases where the precision of application is desired and the reduction in the potential migration of the system in the area or to the surrounding tissues. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage. The addition of hyaluronate serves as an adjuvant to aid in the physiological process of healing. EXAMPLE 20 Sodium hyaluronate 2.5% Saline for injection, USP 5% Glyceryl monooleate 92.5% Glyceryl monooleate (GMO) was heated to melt. The sodium hyaluronate was dispersed with agitation in the GMO. The normal saline solution was combined with a mixture of GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 1000-3000 centipoise. The present example possesses features that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue, in cases where the precision of application and reduction in the potential migration of the system in the area or to the surrounding tissues. The formulation can also be used in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the surface of the wound. the burn of the abrasion and new injury / loss of tissue after the change of bandage. The addition of hyaluronate serves as an adjuvant to aid in the physiological process of healing. EXAMPLE 21 Hydrogenated lecithin 5% Saline for injection, USP 5% Glyceryl monooleate 90% The hydrogenated lecithin was dispersed in the saline solution and heated to approximately 40 ° C. Glyceryl monooleate (GMO) was heated to molten. The hydrogenated lecithin solution was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 50,000-100,000 centipoise. The present example possesses features that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue, in cases where the precision of application and reduction in the potential migration of the system in the area or to the surrounding tissues. The addition of lecithin serves as a source of physiological phospholipid intermediates to accentuate the normal host coagulation cascade.

EXAMPLE 22 Hydrogenated Lecithin 5% Saline for injection, USP 5% Glyceryl monooleate 90% Glyceryl monooleate (GMO) was heated to melt. The hydrogenated lecithin was dispersed with agitation in the GMO. The normal saline solution was combined with a mixture of GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 1000-3000 centipoise. The present example possesses features that make it operable as a hemostatic agent in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial or internal wounds and affected tissue, in cases where the precision of application and reduction in the potential migration of the system in the area or to the surrounding tissues. The addition of lecithin serves as a source of physiological phospholipid intermediates to accentuate the normal host coagulation cascade.

EXAMPLE 23 Propylene glycol, USP 5% Water for injection, USP 2.5% Ethanol, USP 2.5% Glyceryl monooleate 90% heated glyceryl mono-oleate (GMO) until melted. propylene glycol, water for injection and ethanol were combined and mixed well to form a homogeneous solution. The solution of molten GMO and PG / water / ethanol were combined with vigorous mixing. The resulting system was allowed to return to room temperature without disturbance. The resulting mixture produced a clear to hazy liquid formulation with a viscosity in the approximate range of 80-200 centipoise. This formulation is suitable for hemostatic applications by low and high pressure administration methods. After the elaboration, the formulation was placed inside an aerosol system with compressed air. The formulation is easily applied to ratios that range from a fine mist to a coarse spray. This method of administration is allowed for a convenient and uniform application over a large surface area. The present example possesses characteristics that make it particularly operable as an agent for fluid control, and / or agent for wound healing in formulations for use in a direct application by spray to burns, or in articles for wound dressing for the treatment of burns of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, control of fluid (exudation) and protecting the burn surface from abrasion and re-injury / loss of tissue after bandage change.

EXAMPLE 24 Propylene glycol, USP 2.56% Water for injection, USP 5.1% Glyceryl monooleate 92.3% Glyceryl Monooleate (GMO) was heated to melt. The propylene glycol and water for injection were combined and mixed well to form a homogeneous solution. The molten GMO and the PG / water solution were combined with vigorous mixing. The resulting system was allowed to return to room temperature without disturbance. The resulting mixture produced a clear to hazy liquid formulation with a viscosity in the approximate range of 3000-5000 centipoise. The present formulation is suitable for hemostatic applications by methods of administration at low and high pressure. After processing, the formulation was placed inside a pump-type spray bottle. The formulation is easily applied as a thin stream and a coarse spray. This method of administration allows convenient and direct application to a specific tissue surface area. The present example possesses features that make it particularly operable as an agent for fluid control, and / or wound healing agent in formulations for use in direct spray application to burns, or in articles for wound dressing for the treatment of burns. of variable degree, to protect the surface of the burn from exposure to microorganisms thus inhibiting infection, fluid control (exudation) and protecting the burn surface from abrasion and re-injury / tissue loss after bandage change .

EXAMPLE 25 Thrombin 1000 U / g Saline solution for injection, USP 5% Glyceryl monooleate 95% Saline solution for injection, USP, was heated at approximately 40 ° C. Glyceryl monooleate (GMO) was heated to molten.

The saline was combined with GMO. The resulting system was mixed well and allowed to return to room temperature without disturbance. Thrombin was dispersed in the system with gentle mixing. The resulting mixture produced a misty liquid formulation with a viscosity in the approximate range of 80-500 centipoise.

The present example possessed a lower viscosity which makes it operable as a hemostatic agent for administration by means of washing or irrigation as well as by pressurized methods of administration to superficial or internal wounds and affected. The addition of thrombin served an adjunct role as a physiological mediator to supplement the normal coagulation cascade.

EXAMPLE 26A Plasma, platelets, platelet-rich plasma, or whole blood ~ 1 to -45% by weight Glyceryl monooleate ~ 35 to -99% by weight EXAMPLE 26B Plasma, platelets, platelet-rich plasma, or whole blood ~ 6% by weight Glyceryl monooleate ~ 94% by weight Platelets, platelet-rich plasma, plasma or disease-free total blood, drug-free, from a patient to be treated, or another acceptable donor source of blood, heated at approximately 40 ° C. The glyceryl mono-oleate (GMO) is heated until molten. The platelets, platelet-rich plasma, plasma or whole blood are then combined with G O. The resulting system is mixed well and allowed to return to room temperature without disturbance. The resulting mixture produces a liquid formulation with a relatively low viscosity. The present example possesses characteristics that make it operable as a hemostatic agent, for fluid control, and / or wound healing in formulations for administration by means of washing or irrigation, as well as by pressurized methods of administration, to superficial wounds or internal, and affected tissue. It is considered that many if not most of the other formulations previously specified in Examples 1 -25 can be formulated with donor-grade platelets, platelet-rich plasma, plasma or whole blood, either in place of the described solvent, or in addition of, to create formulations suitable for a variety of hemostatic purposes, for fluid control and / or for wound healing purposes.

EXAMPLE 27 An absorbent article In one embodiment, there is provided an absorbent layer comprising an outer layer impervious to liquid and permeable to moisture vapor having an inner surface and an outer surface, the internal surface essentially coextensive with an outer surface of the absorbent layer. The liquid permeable coating may have a surface that is essentially coextensive with an inner surface of the absorbent layer such that the absorbent layer is located between the liquid permeable cover and the outer layer. In addition, the article has a biocompatible biodegradable hydrophobic composition in at least a portion of an opposite surface of the liquid permeable coating which is coextensive with the inner surface of the outer layer, wherein the composition comprises from about 50% to 99% by weight. weight of a compound that forms liquid crystal and approximately 0% to 50% by weight of solvent. When the absorbent device is used as a wound dressing, it can be placed on the wound with the absorbent layer located adjacent to the wound. The device can then be adhered to the skin around the wound, for example, by tape or an adhesive wrap. In another embodiment, the absorbent layer and the outer layer are not substantially coextensive and the other layer extends beyond at least a portion of the outer perimeter of the absorbent layer to form an extended portion with an upper and lower surface. The lower surface of the extended portion is adjacent to the absorbent layer and at least a portion of the lower surface carries an adhesive layer which can be used to adhere the absorbent article to the skin around a wound. Optionally, this embodiment may additionally comprise a coating for release that is substantially coextensive with the outer layer and adheres to the liquid permeable coating by the adhesive layer. The release liner could then be removed from the absorbent article before application to the wound or site of application of the article. The liquid-permeable layer allows the passage of a liquid, eg, exudate, from the wound or treatment site to the absorbent layer, and preferably prevents adhesions of the absorbent layer at the application site of the article. Aqueous media absorbent devices will often comprise an outer layer substantially impermeable to the aqueous medium and permeable to moisture vapor, which may comprise any suitable material, such as polyethylene, polypropylene and polyurethane, with a thickness of approximately 0.02 mm to help retain the fluid inside the absorbent material. The outer layer may also comprise a fabric treated with a water repellent material. The outer layer may also be a film coated with moisture vapor permeable adhesive as described in the U.S. Patent. No.4,726,989. The liquid permeable layer can comprise any material, such as polyester, polyolefin, rayon, and the like, which is substantially porous and allows the aqueous medium to pass easily therethrough to the underlying absorbent core. Examples of suitable adhesives for the adhesive layer include any of the non-cytotoxic adhesives such as hot melt spray adhesives including HL-1685-X or HL-1710-X, both commercially available from HB Fuller Co., St. Paul, MN The hot melt adhesive can be applied using spiral spray adhesive systems such as those commercially available from Nordson Corporation, Duluth, GA. The typical adhesive application rates using such systems are approximately 6 to 10 grams / m2. The absorbent layer may comprise fibers combined with materials commonly used to prepare absorbent fabrics or cotton sheets, such as wood pulp, cellulose, cotton, rayon, recycled cellulose, shredded cellulose sponge and binders, or crumbled keratin. Typically the thickness of the absorbent layer is from about 0.5 to 10 mm. The release liner can be any polymeric film, paper or aluminum foil known in the art to be used as a release liner. Examples of useful release coatings include 50 g / m2 based on weight of SC 50 FM40 white Sopal Flexible Packaging available from Day Cedex, France. The modalities as described may be bandages, gauze bandages, sponge bandages, or any other absorbent article, with added adhesive or simply the article only, prepared under sterile conditions and pre-packaged in sterile packages for direct use in a wound or another desired site.

EXAMPLE 28 Utility as a hemostatic system - hepatic lacerations in a murine model Animal # 1 - an adult rodent was anesthetized, and then the tail was completely lanced to produce a strong arterial bleeding in saline at 37 ° C. After two minutes without decrease or cessation, the glue was removed from the saline and a drop of formulation # 2 was applied. The bleeding stopped after ~ 1 min, a slow exudation started. This secondary bleeding stopped completely with the second application. Animal # 2- Bleeding of the tail was induced as in animal # 1. After 10 seconds in saline at 37 ° C the glue with heavy bleeding was removed from the saline solution and coated with a drop of formulation # 2. This greatly decreased the bleeding with some output by blood pressure. A second and third drop of formulation # 2 controlled the bleeding to a large extent, but not completely. A transverse laparotomy was performed to expose the abdominal cavity. In the process of liver exposure, bleeding occurred from an unintentional wound of a main blood vessel (not identified). Bleeding from this wound was completely controlled with two drops of formulation # 2. Animal # 3- After the establishment of a plateau of anesthesia and to perform transverse laparotomy, the liver was lanced and left to bleed freely on the gauze for 30 seconds, at which time the surface of the laceration and the surrounding tissue It was filled freely with formulation # 2. The bleeding was quickly controlled. The gauze with an excess of formulation # 2 was removed after one minute, and then a second piece of gauze was placed under the lacerated organ. A minimum of blood was deposited from the site of the wound in the second piece of gauze. Bleeding of the tail was induced as in animal # 1, and then completely controlled with two drops of formulation # 2. General conclusions that refer to in vivo bleeding experiments- The application of formulation # 2 successfully controls bleeding that originated in capillaries and small blood vessels capillaries. Bleeding from major arteries may require a matrix impregnated with GMO for mechanical strength.

EXAMPLE 29 Utility as hemostatic system - hepatic lacerations in a murine model Eight male Sprague-Dawley rats (400-450 g) were anesthetized using ketamine 90 mg / kg and xylazine 10 mg / kg i.p. After the induction of anesthesia, a laparotomy was performed to expose the liver. The middle lobe dissections were carried out first to remove approximately 25% of the lobe mass followed by the treatment and by a second lesion representing the cross section of a middle lobe removing approximately 50% of the lobe mass. The application of the formulation provided in Example 2 applied by irrigation and positive pressure spray techniques were able to control bleeding in all animals (n = 8) within the first 20 seconds (range 10-45 seconds) compared with control animals that bled due to model lesions within the first 5-10 minutes. The control of the hemorrhage was confirmed for a period of 30 minutes and subsequently the animals were euthanized.

EXAMPLE 30 Utility as a haemostatic-cross section system of the saphenous vein in a murine model Eight male Sprague-Dawley rats (400-450 g) were anesthetized using ketamine 90 mg / kg and xylazine 10 mg / kg i.p. After the induction of anesthesia, the groin was dissected to expose the superficial saphenous vein. The vein was cut transversely by a particular perpendicular incision. The application of the formulation provided in Example 2 was applied by irrigation and positive pressure spray techniques were able to control bleeding in all animals (n = 8) within the first 10-45 seconds compared to control animals who bled from model lesions within the first 6-10 minutes. The control of the hemorrhage was confirmed for a period of 30 minutes and subsequently the animals were sacrificed.

EXAMPLE 31 Utility as hemostatic system - hepatic lacerations in a pig model A farm pig weighing approximately 30 kg was anesthetized and a transverse laparotomy was performed to expose the liver. The liver was cut transversely to approximately 2.5 cm from the lateral border to produce a diffuse capillary bleeding lesion which, if left untreated, represents a lesion that can cause bleeding in approximately 10 minutes. The lesion was treated with an irrigation consisting of Rylo MG 19 (Danisco Corp.) 94.5%, dodecane 5% and epinephrine 0.5%. After a single application of approximately 10 ml, bleeding was well controlled with a minor exudate observed in the lesion. A subsequent wound was inflicted by removing a portion of the hepatic lobe approximately 5 cm from the outer margin. This lesion resulted in a capillary extended lesion with the cross section of multiple arterioles that could result in death in 5 minutes or less without support and control treatment. An irrigation of the Rylo / dodecane / epinephrine formulation again maintained adequate control of capillary bleeding. This was not adequate for arterial injuries. However, a gauze impregnated with Rylo / dodecane / epinephrine was applied to the lesion. The application maintained adequate control of capillary and arterial bleeding while in that location. Once the gauze was removed, hemostasis was maintained within the capillary bed, however arterial lesions were not well controlled.

EXAMPLE 32 Utility as a hemostatic system - traumatic oral laceration A 4-year-old white female subject presented with a traumatic laceration adjacent to the lower right bicúpsides secondary to a fall in a playground. The laceration bled freely after attempts to apply pressure and cold compresses for approximately 5 minutes. Approximately 1 ml of a formulation described in example # 2 was applied to the lesion. Hemostasis was established within the first 30 seconds with no additional need for subsequent treatment. A white female subject of 2 years of age presented with a traumatic laceration adjacent to the lower incisors secondary to an inadvertent collision with another child. The laceration bled freely after attempts to apply pressure and cold compresses for approximately 3-5 minutes. Approximately 1 ml of a formulation described in example # 2 was applied to the wound. Hemostasis was established within the first 30 seconds with no additional need for subsequent treatment.

EXAMPLE 33 Utility as a canine hemostatic-bite system A 38-year-old white man presented with a particular puncture wound and laceration of approximately 1.5 cm in length in the anterior part of the distal phalanx of the left thumb that extended towards the nail that bled freely despite the application of direct pressure. Subsequently, approximately 0.5 ml of a formulation described in example # 2 was applied to the wound. The initial application formed a gel on the puncture site, however the bleeding was not completely controlled. A subsequent application of the preformed gel was carried out within the pressure puncture site. The second application established haemostasis within the first 30-45 seconds with only a minor exudate of the wound for a period of 2-4 days after the injury.

EXAMPLE 34 Utility as a hemostatic-epistaxis treatment system A 37-year-old white man with a medical history without previous events presented with acute, spontaneous epistaxis. Conventional treatment and pressure showed no benefit after 5-10 minutes. The application of approximately 0.25 ml of a formulation described in example # 5 was achieved using a cotton swab. After application, the nostrils were compressed for approximately 10 seconds to disperse the material in the nasal cavity. Immediate haemostasis was achieved after the particular application without additional bleeding.

EXAMPLE 35 Utility as a therapeutic / protective system for wound care-Ulcerations on the pad of a dog's paw A 9-year-old Yorkshire Terrier with a previous medical history of diabetes and seizure disorder presented with extensive ulcerations on the paws of the paw on all four legs making his walk incredibly difficult. The wounds of the animal's right front and left rear pads were cleaned and bandaged every third day with the formulations described in example # 2 and 26B respectively; the right front and left rear pads were only cleaned and bandaged without treatment. Over a period of 30 days, the ulcerations of the treated pads improved and healed at a significantly faster rate than the untreated pads, which improved little if they did. The treated pads showed resolution of the ulcerations within a period of 30 days. In addition, an untreated ulcer was infected before the conclusion of the 30-day window. The other untreated ulcer was infected in the week after the 30-day period. Both treated ulcers healed without signs of infection.

EXAMPLE 36 Utility as a protective system for wound-throat care with streptococcus A 36-year-old white male presented with deep pain in the oropharyngeal area secondary to acute tonsillitis and streptococcal A infection. A formulation consisting of 85% GMO and PEG 400, 10% and PEG 200, 5% was applied. using a cotton swab. The system formed a protective gel that covered the inflamed region allowing pain relief and fluid consumption for approximately a period of 4 hours. The described embodiments of the invention are intended to be merely exemplary and numerous variations and modifications will be apparent to those skilled in the art. Different brands of particular ingredients can be used, and other compounds having similar physicochemical properties can be exchanged with those described to produce alternative formulations with desired hemostatic characteristics, wound healing, fluid absorption, antimicrobial and / or pain relief characteristics. All such variations and modifications are intended to be within the scope of the present invention as defined in the appended claims.

EXAMPLE 37 Utility as a therapeutic / protective system for wound-burn care A patient suffering from second and third degree burns was treated with an absorbent article as described in example 27, wherein an article of wound dressing, its surface impregnated or coated with formulations for wound healing, for fluid absorption as described in Examples 1-6, 9, 11, 16, 19, 20, and 23 and 24, especially, it is applied to the area of the burn after cleaning. The surface of the burn is cleaned and sold every third day, every day, or more frequently, as necessary, with a sterile absorbent article containing a formulation as described. As a control, comparable burn areas were treated with other conventional wound dressing articles and burn treatment formulations at the same time, with cleanup of the burn surface and identical dressing procedures for both the control areas and for the control areas. burn areas treated with formulations described in the present invention. The burn areas treated with the absorbent articles impregnated or coated with formulations as described in the present invention improved and healed at a significantly faster rate than the areas that were treated with conventional wound dressing articles and burn treatment formulations. In addition, there is significantly less tissue removal after dressing change when absorbent articles and wound dressing articles are used in the present invention., which have the formulations described above in the present invention present in or on the material or surface of the wound dressing article, and were observed to heal faster, with less exudate and infection. Alternatively, the burn area can be treated with formulations from Examples 1-6, 9, 11, 19, 20, 23 or 24 by spraying, coating, bathing, or otherwise applying the formulation directly to the burn. burn area, with the bandage for wound material, such as a conventional gauze or other bandage applied after the application of the formulation described in the present invention.

EXAMPLE 38 Utility as a protective system for wound care-open sore A patient suffering from an open sore, such as a sore, abrasive burn, caustic burn, or similar wound that creates an opening, arrives to exude, is treated with an absorbent material as described in example 27, wherein an article of bandage for wound, its surface impregnated or coated with a formulation for wound healing, absorption of fluids described in the previous examples is applied to the area of the open sore after cleaning. The sore surface is cleaned and bandaged every third day, every day, or more frequently, as necessary, with a sterile absorbent article containing a formulation as described. As a control, comparable areas of the sore are treated with other conventional wound dressing articles and formulations for open sore treatment at the same time, with sore cleaning and identical dressing procedures for both the control areas and the control areas. areas with sores treated with formulations described in the present invention. Areas with open sores treated with absorbent articles impregnated or coated with formulations as described in the present invention improved and healed at a significantly faster rate than areas treated with conventional wound dressing articles and with formulations for treating open sores. . In addition, there is significantly less tissue removal after bandage change when absorbent articles and wound dressing articles are used as described in the present invention, which have formulations described above present in or on the wound dressing article material or surface, and faster healing is observed, with less exudate and infection. Alternatively, the area of the open sore can be treated with formulations from the examples described above by spraying, coating, bathing, or otherwise applying the formulation directly on the open area of the sore, with the bandage material for wound, such as a conventional gauze or other bandage, applied after application of the formulation described in the present invention. The disclosed embodiments of the invention are intended to be merely exemplary and numerous variations and modifications will be apparent to those skilled in the art. Different brands can be used for particular ingredients, and other compounds having similar physicochemical properties can be exchanged with those described to produce alternative formulations with desired hemostatic characteristics, wound healing, fluid absorption, antimicrobial characteristics and / or for pain relief. . All such variations and modifications are intended to be within the scope of the present invention as defined in the appended claims.

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1 .- A therapeutic formulation adapted for application at positive and effective pressure to control the biological fluid at a desired site in a subject, the formulation comprising: from about 25% to about 99% by weight of a compound that forms liquid crystal; and from 0% to about 75% by weight of an enhancing or therapeutic agent selected from the group of a solvent, a fatty acid or a combination thereof, wherein the formulation effectively controls the biological fluid at the desired site in the subject. 2. - An infection resistant device for placement in a desired site of a subject, the device designed with an anti-infective formulation comprising from about 25% to about 99% by weight of a compound that forms liquid crystal; and from 0% to about 75% by weight of an enhancing or therapeutic agent selected from the group of a solvent, a fatty acid or a combination thereof, wherein said anti-infective formulation inhibits growth formation of the pathogen in the device, or in adjacent tissues, thus imparting resistance to infection. 3. The use of an anti-infective formulation comprising from about 25% to about 99% by weight of liquid crystal-forming compound; and from 0% to about 75% by weight of an enhancing or therapeutic agent selected from the group of a solvent, a fatty acid or combination thereof, for the manufacture of an infection resistant device useful for treating an acute wound or chronicle. 4. The use of a formulation comprising: from about 25% to about 99% by weight of compound that forms liquid crystal; and from 0% to about 75% by weight of an enhancing or therapeutic agent selected from the group of a solvent, a fatty acid or combination thereof, for the manufacture of a medicament useful for controlling bleeding and for providing hemostasis in a site desired in a subject, wherein the medicament is adapted for application to positive pressure on or within tissue and having its effects in approximately 15 minutes or less, thus controlling bleeding. 5. - The formulation according to claim 1, further characterized in that said liquid crystal forming compound can be any of: a fatty acid, monoester fatty acid, fatty acid diester, fatty acid triester or combinations thereof, which additionally comprises at least one unsaturated carbon-carbon bond. 6. - The formulation according to claim 5, further characterized in that said liquid crystal forming agent is a glyceryl monoester, diester, triester, or combinations thereof. 7. - The formulation according to claim 6, further characterized in that said liquid crystal forming agent is glyceryl monooleate. 8. An effective hemostatic formulation for controlling bleeding at a desired site in a subject, the composition comprising: from about 25% to about 99% by weight of glyceryl monooleate as a compound that forms liquid crystal; and from 0% to about 75% by weight of an enhancing or therapeutic agent selected from the group of a solvent, a fatty acid or a combination thereof, wherein the hemostatic formulation is adapted for application at positive pressure on or in the tissue affects hemostasis and induces local effects at the desired site in approximately 15 minutes or less, thus controlling bleeding. 9. - A thrombin inhibitory formulation comprising approximately 25% to 99% by weight of glyceryl monooleate, glyceryl monoerucate or combinations thereof, and from about 0% to about 75% by weight of an enhancing or therapeutic agent selected from from the group of a solvent, a fatty acid or a combination thereof, wherein the formulation is adapted for application at positive pressure to the desired site in a subject. 10. - The thrombin inhibitor formulation according to claim 9, further characterized in that the formulation is a neuroprotective agent. eleven . - An absorbent medical or hygienic article or device having a formulation of any of claims 1, 8 or 9 present within or in at least a portion of the article or device. 12. - A cosmetic formulation effective to mimic soft tissue at a desired site in a subject, the formulation comprising: from about 25% to 99% by weight of a liquid crystal-forming compound; from about 1% to about 75% by weight of a solvent; and other compounds, as required, to provide effective viscosities and textures to mimic soft tissue. 13. The use of a therapeutic formulation of any of claims 1, 8 or 9 for the manufacture of a medicament useful for effectively controlling a biological fluid at a desired site in a subject. 14. The use as claimed in claim 13, wherein the medicament is useful to promote hemostasis at the desired site. 15. The use as claimed in claim 13, wherein the medicament is useful to promote coagulation at the desired site. 16. - The use as claimed in claim 13, wherein the medicament is useful for facilitating healing by inducing local effects at the desired site. 7. The use as claimed in claim 16, wherein the medicament is useful for maintaining moisture at the desired site. 18. - The use as claimed in claim 3, wherein the medicament is adapted to be administrable as a tissue filler, which has an increased residence time at or near the desired site, such that the formulation resists the elimination from the body. 19. The use as claimed in claim 13, wherein the medicament is useful to form a protective seal at the desired site, in order to control the flow and exchange of biological fluids and promote tissue healing via the formation of a protective barrier on the site. 20. The use as claimed in claim 13, wherein the medicament is useful for delaying the formation of a surgical adhesion, in order to inhibit the formation of unwanted post-operative scar tissue that may result in or adjacent to a surgical site. twenty-one . - The use of the thrombin inhibitor formulation of claim 9, for the manufacture of a medicament useful for controlling the loss of blood at a site in a subject, wherein said medicament facilitates the coagulation of the blood, thereby controlling the loss of blood. blood on the site. 22. The use of the formulation of any of claims 1, 8 or 9 for the preparation of a medicament useful for carrying out the sealing of the tissue at a desired tissue site, wherein the tissue is selected from the group consisting of epithelial, connective, skeletal, glandular, muscular and neural tissue. 23. - The use as claimed in claim 22, wherein the desired site is neural tissue thereby controlling the flow of neural biological fluids to inhibit the progression of paralysis. 24. - The use as claimed in claim 22, wherein the desired site is bone tissue and the medicament is useful for sealing the bone, thus inhibiting the loss of biological fluids and providing a protective barrier in the opening. 25. The use of a formulation of any of claims 1, 8 or 9, for the preparation of a drug useful for inducing a therapeutic plunger, wherein the drug is adapted to be administrable by direct injection into the circulatory system of the subject thus providing a means for embolic therapy. 26. The use of a formulation of claim 12, for the manufacture of a medicament useful for effectively imitating soft body tissues at a desired site in a subject, wherein the medicament is adapted to be internally administrable at the desired site to mimic the soft tissues. 27. The use as claimed in claim 26, wherein the medicament is adapted for use as filling means for a cosmetic and / or reconstructive implant device. 28. - A method for imparting resistance to infection in a device for location at a desired site of a subject, the method comprising: designing the device with an anti-infective formulation comprising from about 25% to about 99% by weight of the compound that liquid crystal form; and from 0% to about 75% by weight of an enhancing or therapeutic agent selected from the group of a solvent, a fatty acid or a combination thereof, wherein said anti-infective formulation inhibits the growth of the pathogen in the device, or in adjacent tissues, thus imparting resistance to infection. 29. - The use of a formulation comprising from about 25% to about 99% by weight of compound that forms liquid crystal; and from 0% to about 75% by weight of an enhancing or therapeutic agent selected from the group of a solvent, a fatty acid or combination thereof, wherein said anti-infective formulation inhibits the growth of pathogens, for the preparation of a useful device for the treatment of an acute or chronic wound. 30. - The use of a formulation of any of claims 1, 8 or 9 for the preparation of a medicament useful for increasing the residence time of the therapy at a site in a subject, wherein the medicament provides residence time increased and attenuated removal from the desired site or by forming a viscous liquid crystalline state thus decreasing the tendency to remove more fluid states from the desired site. 31. The use of a formulation of any of claims 1, 8 or 9, for the preparation of a medicament useful for administering therapeutic degradation products at a site in a subject, wherein the medicament functions as a system for administration with controlled release for degradation products of the compound forming liquid crystal, wherein said degradation products provide an anti-infective effect. 32. The use of a formulation of any of claims 1, 8 or 9, for the manufacture of a medicament useful for filling tissue voids in a site in a subject, wherein the medicament is effective as a filling of a vacuum of tissue, such as those created by trauma, disease or a surgical procedure. 33. The use of a formulation of any of claims 1, 8 or 9, for the preparation of a medicament useful for inhibiting the adhesion of articles or medical devices to body tissues thereby reducing the trauma of application or removal, in wherein the medicament is adapted to be an integral coating, or to be applied to the tissue just prior to the application of the articles or medical devices. 34. The use of a formulation of any of claims 1, 8 or 9, for the preparation of a medicament useful for treating an acute or chronic wound including an abrasion, a burn, a laceration, a puncture, an incision, a surgical wound, an ulceration, a leg ulcer, a decubitus ulcer, a fungal ulcer, a diabetic ulcer, a foot ulcer, a sacral ulcer, an indolent ulcer, or a combination thereof. 35. The formulation according to any of claims 1, 8 or 9, further characterized in that the formulation is administrable by direct or indirect administration in the form of: irrigation, continuous spraying, intermittent spraying, direct current, intermittent, washing, shower, enema, implant, injection, deposition, manual administration or by incorporation with a medical article. 36. - The article or medical device according to any of claims 2 or 11, further characterized in that the article or device is any of a wound dressing, a medical sponge, a hemostatic article, an article for naso-sinus, a bandage, a wound protective material, a protective material for internal vascular closure, a bandage for external vascular closure, a swellable absorbent article, a fibrotic wound protective article material, an implantable medical article, or a product for feminine hygiene. 37.- The formulation according to any of claims 1, 8 or 9, further characterized in that the formulation is a liquid, gel or semi-solid. 38. - The formulation according to any of claims 1, 8 or 9, further characterized in that the formulation is biocompatible and / or biodegradable. 39. - The formulation according to claim 1 or 9, further characterized in that the liquid crystal forming compound is selected from the group of a fatty acid, a fatty acid ester, a glycolipid, a phospholipid, a polyethylene oxide , a polyester, a polyethylene glycol or a combination thereof. 40. The formulation according to claim 1 or 9, further characterized in that the fatty acid ester is selected from the group of glyceryl monoarachidonate, glyceryl monolinoleate, glyceryl monolinolenate, glyceryl monopalmitoleate, glyceryl monooleate, glyceryl monocolagenate, glyceryl monoerucate, glyceryl monolinoleate, glyceryl monolinolenate, glyceryl monopentadecanoate, glyceryl monopolyacrylate, glyceryl monoceboate, isopropyl monoarachidonate, isopropyl monolinoleate, isopropyl monolinolenate, isopropyl monopalmitoleate, isopropyl monooleate; methyl monoarachidonate, methyl monolinoleate, methyl monolinolenate, methyl monopalmitoleate, methyl monooleate, propylene glycyl monoarachidonate, propylene glycol monolinoleate, propylene glycol monolinolenate, propylene glycyl monopalmitoleate, propylene glycyl monooleate, or combinations thereof. 41. - The formulation according to any of claims 1, 8 or 9, further characterized in that the solvent is a polar solvent selected from the group of water, any aqueous liquid including biological fluids, various alkanols, polyethylene glycol, propylene glycol, polypropylene glycol , glycol, glycerin, isotonic aqueous solution, systems with physiological pH or combinations thereof.