RU2433834C2 - Porous biologically absorbable bandage which includes microspheres and method of its manufacturing - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine. Described is method of manufacturing biologically absorbable bandage, which includes envelope and biologically absorbable microspheres, in form of tourniquet. Additionally bandage envelope contains pores, formed by pore-forming system, which can be activated by external way relative to wound, or form in situ within wound surface. Bandage shape makes it possible to place the bandage on wound surface in such a way that it fills wound by shape and size. Described are bandages in form of tourniquet and their application in combination with treatment by reduced pressure is shown.

EFFECT: bandage in form of tourniquet is easy adapted to size and shape of any wound surface.

25 cl, 11 dwg

Description

BACKGROUND OF THE INVENTION

Technical field

This invention generally relates to methods, systems and compositions for the manufacture and use of porous, bioresorbable dressings, including bioresorbable microspheres, for use in connection with the treatment of wounds under reduced pressure.

Description of the Prior Art

Wound healing in a broad sense can be divided into three main overlapping phases: inflammation, cell proliferation, and maturation. The inflammatory phase is characterized by hemostasis and inflammation. The next phase consists mainly of epithelization, proliferation of blood vessels, the formation of granulation tissue and deposition of collagen. The final phase includes maturation and reconstruction. The complexity of this three-step wound healing process increases under the influence of local factors such as local anemia, edema and infection, and systemic factors such as diabetes, age, hypothyroidism, malnutrition and obesity. However, often the stage that limits the rate of wound healing is the proliferation of blood vessels. The growth of blood vessels in the wound is characterized by the migration of endothelial cells and the formation of capillaries, while the growth of capillaries in the wound bed is crucial to maintain tissue regeneration. The granulation phase and tissue formation require nutrition supplied by these capillaries. Thus, worsening of the proliferation of blood vessels in a wound can lead to chronic, problematic wounds.

The manifestation of the angiogenic phenotype is a complex process that requires that a large number of events occur in the form of successive stages at the cellular and molecular levels. Some of these activities include the growth of endothelial cells, the degradation of the surrounding base membrane, the migration of endothelial cells through the stroma of connective tissue, the formation of tubular structures and the development of tubes lined with endothelium into new blood vessels. The proliferation of blood vessels is controlled by accelerating and slowing regulators. In addition to endothelial cells, tissue repair cells such as platelets, monocytes, and phagocytes secrete factors causing blood vessel growth, such as vascular endothelial growth factor (VEGF), which initiate the growth of blood vessels, in damaged areas. vessels.

Currently, there are several methods used to accelerate wound healing, including washing the wounds to remove toxins and bacteria, local or systemic use of antibiotics and anesthetics, and local application of growth factors. One of the most successful ways to accelerate wound healing when injuring soft tissues that heal slowly or are non-healing is low pressure treatment. Under reduced pressure treatment is usually meant to apply less pressure to the wound area than ambient pressure, and the magnitude and duration of the reduced pressure treatment are sufficient to promote healing or tissue growth. Examples of devices used for applying reduced pressure include devices that have been popularized by Kinetic Concepts, Inc. Of San Antonio, Texas, through their commercially available VACUUM ASSISTED CLOSURE® or V.A.C. The healing process induced by the reduced pressure has been described in US Pat. Nos. 5,636,643 and 5,645,081, the disclosures of which are incorporated herein by reference in their entirety.

Low blood pressure serves to accelerate the migration of epithelial tissue and subcutaneous tissue from healthy tissue to the wound surface. Typically, reduced pressure treatment involves applying reduced pressure to the wound surface through a dressing that serves as a manifold for distributing the reduced pressure. This dressing has a size corresponding to the size of an existing wound; it is placed in contact with the wound, and then periodically replaced with smaller dressings as the wound begins to heal and decreases. Although the use of the reduced pressure treatment with dressing has been highly successful, there are still various difficulties associated with this process. For example, it may be difficult to obtain a dressing of suitable width, length, or thickness so that it properly matches the wound. Furthermore, since the dressing is removed, it can also remove healthy tissue, thereby causing additional trauma in the wound area.

It has been proposed that biodegradable materials be used to make the dressing, resulting in a dressing that does not need to be removed from the wound area. However, when there are a large number of such dressings, the biodegradable polymer is given a specific shape in advance. Individual wounds, however, have inappropriate shapes and sizes.

Thus, there is a need for a dressing that can be easily made and shaped so that it matches the wound of a particular patient. There is also a need for a dressing that does not need to be removed from the wound surface. In addition, there is a need for a dressing that contains pores, so that this dressing can promote healing and growth of healthy tissue on the wound surface, causing the formation of granulation tissue.

All references cited herein are hereby incorporated by reference to the maximum extent permitted by law. To the extent that any link cannot be fully included in the text of the present description, it is incorporated by reference into the main tasks and is indicative of the knowledge of one of the ordinary specialists in this field.

SUMMARY OF THE INVENTION

These and other problems are solved by applying a bioresorbable dressing in the form of a tourniquet, including bioresorbable microspheres. This configuration allows the dressing to easily adapt to the size and shape of any wound surface. In addition, since the dressing is biodegradable, it does not need to be removed from the wound surface. Thus, in its broadest sense, this invention provides methods, systems and compositions for the manufacture and use of a bioabsorbable dressing made of bioabsorbable microspheres in various configurations.

One example of the implementation of the present invention is a method of manufacturing a bioresorbable dressing for use on a wound surface, which is subjected to treatment with reduced pressure. In this embodiment, at least one bioabsorbable polymer is dissolved in an appropriate solvent. The polymer mixture is then sprayed, dipped, or poured onto a cylinder, and the residual solvent is removed. The obtained bioresorbable polymer in the form of a cylinder is then filled with bioresorbable microspheres. The cylinder is tightened at regular, repeating intervals to obtain a bandage in the form of a tow.

Another embodiment of the present invention is a method of manufacturing a porous, bioresorbable dressing that should be used on a wound surface that is treated with reduced pressure. In this embodiment, at least one bioresorbable polymer is dissolved in an appropriate solvent and mixed with a blowing agent. The polymer mixture is then sprayed, dipped, or poured onto a cylinder, and the residual solvent is removed. Then the obtained bioresorbable polymer in the form of a cylinder is filled with bioresorbable microspheres. Sheath the sheath at regular, repeating intervals to obtain a bandage in the form of a tourniquet.

Another example implementation of the present invention is a method of manufacturing a porous, bioresorbable dressing for use on a wound surface that is treated with reduced pressure. In this embodiment, at least one bioresorbable polymer is dissolved in an appropriate solvent and mixed with a blowing agent. The polymer mixture is then sprayed, dipped, or poured onto a cylinder and the residual solvent is removed. The obtained bioresorbable polymer in the form of a cylinder, i.e. a shell, is exposed to a liquid that reacts with a pore former in the shell to create pores. The shell is filled with bioresorbable microspheres. Then, the sheath is sheathed at regular, repeating intervals to obtain a bandage in the form of a tow.

One example implementation of this invention is a method of manufacturing a bioresorbable dressing, which should be applied on the wound surface, which is subjected to treatment with reduced pressure. In this embodiment, at least one bioabsorbable polymer is dissolved in an appropriate solvent. Then, the resulting polymer mixture is extruded into a precipitant, whereby the polymer mixture is precipitated from the solution. Residual precipitant is removed. Then, the obtained two-dimensional bioresorbable polymer sheet is rolled up in the form of a cylinder to obtain a shell. The cylindrical shell is filled with bioresorbable microspheres and the shell is tightened at regular, repeating intervals to obtain a bandage in the form of a tow.

Another example implementation of this invention is a method of manufacturing a porous, bioresorbable dressing, which should be applied on the wound surface, which is subjected to treatment with reduced pressure. In this embodiment, at least one bioresorbable polymer is dissolved in an appropriate solvent and mixed with a blowing agent. Then, the obtained polymer mixture is extruded onto the surface of the precipitant, as a result of which the polymer mixture is precipitated from the solution. Residual precipitant is removed. Then, the obtained two-dimensional bioresorbable polymer sheet is rolled up in the form of a cylinder to obtain a shell. The cylindrical shell is filled with bioresorbable microspheres, and then the shell is tightened at regular, repeating intervals with the formation of a bandage in the form of a bundle.

Another example implementation of this invention is a method of manufacturing a porous, bioresorbable dressing, which should be applied on the wound surface, which is subjected to treatment with reduced pressure. In this embodiment, at least one bioresorbable polymer is dissolved in an appropriate solvent and mixed with a blowing agent. Then, the resulting polymer mixture is extruded onto the surface of the precipitant, and the polymer mixture is precipitated from the solution. Residual precipitant is removed. Then, the obtained two-dimensional bioresorbable polymer sheet is rolled up in the form of a cylinder to obtain a shell. The resulting shell is exposed to a liquid that reacts with the blowing agent contained in the shell, creating pores. Then the porous membrane is filled with bioresorbable microspheres. Sheath the sheath at regular, repeating intervals to obtain a bandage in the form of a tourniquet.

In yet another embodiment, the invention provides a reduced pressure system for applying a reduced pressure tissue treatment method to a wound surface; the system includes a bioresorbable dressing, including bioresorbable microspheres. In this embodiment, a bioabsorbable dressing is formed by dissolving at least one bioabsorbable polymer in an appropriate solvent. The resulting polymer mixture is then shaped into a cylinder by any means, including, but not limited to, dipping, spraying or pouring the polymer mixture onto the cylinder, or by extruding the polymer mixture onto the surface of the precipitant to produce a two-dimensional polymer sheet that is rolled into a cylinder shape. This cylindrical shell is filled with bioresorbable microspheres, and then the shell is tightened at regular, repeating intervals to obtain a bandage in the form of a tow. Then the dressing is placed on the wound surface so that it matches the shape and size of the wound. The system may further include a manifold placed above the dressing and in fluid communication with the tube to create reduced pressure. The tube for creating reduced pressure is placed in fluid connection with a source of reduced pressure.

In yet another example embodiment, the invention provides a reduced pressure system for applying a tissue treatment method under reduced pressure to a wound surface; the system includes a bioresorbable dressing, including bioresorbable microspheres. In this embodiment, a bioabsorbable dressing is prepared by dissolving at least one bioabsorbable polymer in an appropriate solvent. The resulting polymer mixture is then shaped into a cylinder in any way, including, but not limited to, dipping, spraying or pouring the polymer mixture onto the cylinder, or by extruding the polymer mixture onto the surface of the precipitant to form a two-dimensional polymer sheet that is rolled into a cylinder shape. The cylindrical shell is filled with bioresorbable microspheres, and then the shell is tightened at regular, repeating intervals to obtain a bandage in the form of a bundle. The dressing is placed on the wound surface, so that it matches the shape and size of the wound. The system further includes a manifold located above the dressing and in fluid communication with the tube to create reduced pressure. The tube for creating reduced pressure is further placed in fluid communication with a source of reduced pressure.

In yet another embodiment, the invention provides a method of stimulating new tissue growth and / or healing of a wound surface. The method includes obtaining a bioresorbable dressing in the form of a tow including bioresorbable microspheres. Then the dressing is placed on the wound surface so that it matches the shape and size of the wound, for example, twisting it inside the wound. The method includes placing the collector over the dressing and connecting the collector to the tube to create reduced pressure. Reduced pressure is applied to the wound surface through a biologically absorbable dressing and collector.

In yet another embodiment, the invention provides a method of stimulating new tissue growth and / or healing of a wound surface. The method includes preparing a porous, bioresorbable dressing in the form of a tow including bioresorbable microspheres. Then the dressing is placed on the wound surface, so that it matches the shape and size of the wound. The method includes placing a collector over a bandage, with the manifold attached to the tube to create reduced pressure. Reduced pressure on the wound surface is created through a bioresorbable dressing and collector.

In yet another embodiment, the invention provides a method of stimulating new tissue growth and / or healing of a wound surface. The method includes preparing a porous, bioresorbable dressing in the form of a tow including bioresorbable microspheres. A bioresorbable dressing is first formed by dissolving at least one bioresorbable polymer and a pore former in an appropriate solvent. The resulting polymer mixture is then formed into a cylinder by any means, including, but not limited to, dipping, spraying or pouring the polymer mixture onto the cylinder, or by extruding the polymer mixture into a precipitant to form a two-dimensional polymer sheet that is rolled into a cylinder shape. The shell is brought into contact with a liquid that reacts with a blowing agent included in the shell, forming pores. Then the porous membrane is filled with bioresorbable microspheres and the membrane is screed at certain intervals. Then the dressing is placed on the wound surface so that it matches the shape and size of the wound. The method includes placing the collector over the dressing and connecting the collector to the tube to create reduced pressure. Reduced pressure is applied to the wound surface through a bioresorbable dressing and collector.

In another example implementation of the present invention, a kit for tissue growth and / or healing, designed to stimulate the growth of new tissue on the wound surface. The tissue growth kit includes a bioabsorbable dressing in the form of a tow, including bioabsorbable microspheres, a collector arranged to contact the dressing, and a device for generating reduced pressure.

In another example implementation of the present invention, a form and method for its use to obtain a bioabsorbable dressing comprising bioresorbable microspheres is provided. The shape includes holes on one of the surfaces, and these holes are so large that microspheres can be placed inside them to form capsules. Examples of implementation include the use of bioabsorbable suture materials for adhesion of capsules.

Other objectives, features and advantages of this invention will become apparent upon consideration of the drawings and the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 illustrates a block diagram in accordance with some examples of implementation of the present invention, showing a method of manufacturing a dressing comprising a bioabsorbable shell and bioabsorbable microspheres.

Figure 2 illustrates a block diagram in accordance with some examples of the implementation of the present invention, showing a method of manufacturing a porous, bioresorbable dressing, including bioresorbable microspheres.

Figure 3 illustrates a flowchart in accordance with some embodiments of the present invention, showing a method of manufacturing a porous, bioabsorbable dressing comprising microspheres, wherein the pore-forming system is activated in vivo by placing the dressing in contact with wound fluids.

Figure 4 illustrates a flowchart in accordance with some example embodiments of the present invention, showing a method for manufacturing a bioabsorbable dressing comprising bioabsorbable microspheres in which the dressing is made of extruded polymer.

Figure 5 illustrates a flowchart in accordance with some embodiments of the present invention, showing a method of manufacturing a porous, bioabsorbable dressing comprising bioresorbable microspheres, in which the dressing is made of extruded polymer.

6 illustrates a flowchart in accordance with some example embodiments of the present invention, showing a method for facilitating tissue growth and / or healing by using a reduced pressure system with a bioabsorbable dressing comprising bioabsorbable microspheres.

7 illustrates a flow chart in accordance with some embodiments of the present invention, showing a method for facilitating tissue growth and / or healing by using a reduced pressure system with a porous, bioabsorbable dressing comprising bioresorbable microspheres.

Fig. 8 illustrates a graphical depiction of a device for stimulating new tissue growth and / or healing of a wound surface by applying a bioresorbable polymer dressing comprising bioresorbable microspheres in conjunction with a reduced pressure generation system.

Figure 9 illustrates a graphical representation of a porous, bioresorbable dressing including bioresorbable microspheres.

Figa-C illustrates a graphical representation of the configurations of the forms used to obtain dressings from linked bioresorbable capsules.

11 illustrates a graphical depiction of a dressing of linked bioresorbable capsules formed using the forms of FIGS. 10A-C.

DESCRIPTION OF A PREFERRED EMBODIMENT

In the following detailed description of preferred embodiments, reference is made to the accompanying drawings, which are part of it, and in which, by way of illustration, specific preferred embodiments are shown in which the invention may be practiced. These implementation examples are described in sufficient detail to enable those skilled in the art to implement the invention, and it is understood that other implementation examples can be applied and that logical structural, mechanical, electrical and chemical changes can be made without departing from the spirit and scope of the invention.

In order to avoid details that are not necessary for a person skilled in the art to carry out the invention, this description may omit specific information known to those skilled in the art. Thus, the following detailed description should not be taken in a limiting sense and the scope of the present invention is defined.

All examples of the implementation of this invention include the use of a bioresorbable dressing, which should be used in combination with low pressure therapy to treat a wound surface. The present invention should not be limited by either the specific location of the wound surface or the type of tissue, which is the purpose of applying reduced pressure treatment. Thus, the wound surface that is treated according to this invention may be a site on the surface or inside the body on which it is desirable to stimulate the growth and / or healing of tissue.

The first implementation example in accordance with this invention is a method for producing a bioresorbable dressing that can be placed on a wound of any size, shape or depth and which is able to completely fill the wound due to its configuration in the form of a tourniquet, as illustrated in FIG. A dressing can be used to stimulate tissue growth and / or healing.

The method includes a step (101) of forming a shell by applying one or more bioresorbable polymers. A bioresorbable polymer can be a biocompatible material, the decomposition products of which can be biologically assimilated or excreted from the body naturally. A bioabsorbable polymer may include, but is not limited to, lactide, polylactide (PLA), glycolide polymers, polyglycolic acid (PGA), a copolymer of lactide and glycolide (CoLH), ethylene glycol / lactide copolymers, polycaprolactone (PCL), polyhydroxybenzenes, polyhydroxybenzenes, copolymer of polyethylene glycol and a copolymer of lactide and glycolide, polyoxyacids, polycarbonates, polyamides, polyanhydrides, polyamino acids, polyorthoesters, polyacetals, degradable polycyanoacrylates, polycarbonates, polyfumarates, degradable polyurethanes thanes, proteins such as albumin, collagen, fibrin, synthetic and natural polyaminoacids, polysaccharides such as alginate, heparin, and other naturally occurring biologically resorbable polymers of sugar moieties. Additionally, in one preferred embodiment, the polymer is a PLA: PCL copolymer in which the ratio of PLA to PCL can range from 100: 0 to 0: 100. In some preferred embodiments, the PLA: PCL ratio in the copolymer is about 90:10. In other embodiments, the PLA: PCL ratio in the copolymer is about 80:20. In another example implementation, the ratio of PLA: PCL in the copolymer is approximately 70:30.

One or more bioresorbable polymers are dissolved in an appropriate solvent. The type of solvent used will depend on the biologically absorbable polymer (s) selected. Then the polymer mixture is formed in the form of a cylinder, for example, by spraying, dipping or pouring the polymer mixture onto the cylinder and removing the residual solvent. Examples of solvent removal methods include, but are not limited to, evaporation, oven drying, vacuum drying, and the like. In one embodiment, the solvent is evaporated over a period of about 48 hours.

In an alternative embodiment, one or more plasticizers are added to the bioabsorbable polymer in the solvent. Plasticizers can be any materials that improve the ability to deform the polymer compound, increasing the softness and ductility of this compound. Plasticizers may include, but are not limited to, cetyl alcohol esters, glycerol, glycerol esters, acetylated glycerides, glycerol monostearate, glycerol triacetate, glycerol tributirate, phthalates, dibutyl phthalate, diethyl tertyltratyltratyltratyltratyltratyltratyltiltrate , diethyl sebacinate, dibutyl sebacinate, adipates, azelates, benzoates, vegetable oils, fumarates, diethyl fumarate, malates, diethyl malate, oxalates, diethyl oxalate, succinates, dibutyl succi nat, butyrates, cetyl alcohol esters, salicylic acid, triacetin, malonates, diethyl malonate, castor oil, triethylene glycol and poloxamers.

If one or more plasticizers are included in the polymer, the residual solvent can be removed by any method, such as oven drying or drying under vacuum, until the conditions used begin to promote the evaporation of the plasticizer.

This is followed by operation (102) of forming microspheres from a bioresorbable polymer. Bioresorbable polymer microspheres can be any size that best suits the needs of the artist. While the microspheres are essentially spherical in shape, microparticles of other shapes can also be formed. The microparticles can be in the form of a rectangular parallelepiped, cylinder, rod, cube or have an irregular shape. Additionally, the bioresorbable microparticles may contain growth or healing promoting agents, such as bone morphogenetic protein, fibroblast growth factor, transforming β-growth factor, antibacterial agent, antiviral agent, cell growth promoting agent or other chemically active agents. Additionally, growth promoting or healing agents may be prepared synthetically or naturally, or may be a fragment, derivative or analog of a growth promoting or healing promoting agent.

For all considered examples of the implementation of microparticles can be obtained by any means convenient for the performer. For example, a method for producing microparticles may be a spraying method, as can be seen from US Pat. No. 6,238,705, which is incorporated herein by reference. In addition, the production method employed may be an oil / water emulsion method for producing such polymer microparticles, for example, a method using an oil-in-water or water-in-oil emulsion or oil-in-oil emulsion. Microparticles can also be obtained by a method involving the use of an aqueous two-phase method, which was used to obtain polymer microparticles, for example, as disclosed in the publication of Gehrke et al. (Proceed. Intern. Symp. Control Rel. Bioact. Material., 22, 145-146), which is incorporated by reference. Preferably, a method using an oil-inlet emulsion and evaporation is used to prepare microparticles. In a method using an oil-in-water emulsion, at least one bioresorbable polymer is dissolved in a solvent to form a first mixture. Then this polymer mixture is added to an aqueous solution, preferably containing a surfactant, and intensively mixed, for example, using a stirrer. Then the solvent is evaporated, leaving the resulting microparticles, such as microspheres.

If the microparticles are obtained by emulsion, the diameter of the microparticles depends on the concentration of the polymer and the intensity of mixing. In addition, the size of the microparticles can be controlled by sieving the microspheres. Upon receipt of the microspheres, the microspheres can be in size from about 20 to 1500 microns. Preferably, the microspheres have a diameter in the range of about 20 to 800 microns, and more preferably about 400 microns to 600 microns. For non-spherical microparticles, particles of a similar size are preferred.

This is followed by operation (103), where a bioresorbable polymer or shell formed essentially as a cylinder is filled with bioresorbable microparticles or microspheres. Screeds can be formed on the shell at regular, repeating intervals to form a bandage in the form of a tow. Alternatively, the screeds may be arranged irregularly along the length of the sheath. The step (104) of forming the screeds can be carried out by bending, applying heat, solvents, or forming the screeds on the shell in any other way.

The second example implementation in accordance with this invention relates to a method for obtaining a porous, bioresorbable dressing that can be placed in a wound of any size, shape or depth, and which is able to fill the wound completely due to its configuration in the form of a tourniquet, as illustrated in Figure 2. A dressing can be used to facilitate the growth and / or healing of tissue.

The method includes a step (201) of forming a shell by applying one or more bioresorbable polymers and a pore-forming system. First, one or more bioresorbable polymers are dissolved in a suitable solvent. The type of solvent used will depend on the biologically absorbable polymer (s) selected. A bioabsorbable polymer may include, but is not limited to, lactide, polylactide (PLA), glycolide polymers, poly (glycolic acid) (PGA), a copolymer of lactide and glycolide (CoLH), ethylene glycol / lactide copolymers, polycaprolactone, polyglyphroxybutyrate, polypropylene polyurethane, polypropylene, polybutane, polypropylene, copolymer of polyethylene glycol and a copolymer of lactide and glycolide, polyoxyacids, polycarbonates, polyamides, polyanhydrides, polyamino acids, polyorthoesters, polyacetals, degradable polycyanoacrylates, polycarbonates, polyfumarates, degradable polyurethane s, proteins such as albumin, collagen, fibrin, synthetic and natural amino acids, polysaccharides such as alginate, heparin and other naturally occurring biodegradable polymers from sugar fragments. Additionally, in one preferred embodiment, the polymer is a PLA: PCL copolymer in which the ratio of PLA and PCL can be in the range from 100: 0 to 0: 100. In some preferred embodiments, the ratio in the PLA: PCL copolymer is about 90:10. In other embodiments, the ratio in the PLA: PCL copolymer is about 80:20. In yet another example implementation, the ratio in the PLA: PCL copolymer is about 70:30.

Then, a pore-forming system is added to the biologically absorbable polymer mixture. The pore forming system may include one or more compounds that are capable of creating pores within the shell. The type of pore-forming system is not limited and may include compounds that dissolve when placed in contact with a liquid. This type of pore-forming system includes inorganic salts, such as sodium chloride, sucrose crystals or gelatin beads, which dissolve in liquids such as water. Another type of pore-forming system is a mixture of sodium bicarbonate and acid. When sodium bicarbonate and acid are placed in contact with a liquid, bicarbonate and acid react with the formation of gaseous carbon dioxide. This gas can then increase pore size. The pore-forming system can be used in stoichiometric amounts. You can also imagine that the pore-forming system is used in non-stoichiometric quantities.

In one embodiment, the pore-forming system is sodium carbonate and acid. An acid may be any acid that is not in liquid or gaseous form, and thus exists in a solid or crystalline state. Examples of suitable acids that can be used in this invention include, but are not limited to, citric acid.

In an alternative embodiment, the pore-forming system is a salt. The invention is not limited to the type of salt, provided that the salt has an appropriate particle size and is soluble in a fluid, i.e. a gas, liquid or fluid material, including, but not limited to, colloids, creams, liquid, suspension, suspension, viscous gel, paste, mastic and particulate solids. Examples of suitable salts used in the present invention are, but are not limited to, sodium chloride and potassium chloride.

Then, the polymer mixture is molded in the form of a cylinder, for example, by spraying, dipping or pouring the polymer mixture onto the cylinder and removing the residual solvent. Examples of solvent removal methods include, but are not limited to, evaporation, oven drying, vacuum drying, and the like. In one embodiment, the solvent is evaporated over a period of about 48 hours.

In an alternative embodiment, one or more plasticizers are added to the bioabsorbable polymer in the solvent. If one or more plasticizers are included in the polymer, then the residual solvent can be removed by any method, such as oven drying or drying under vacuum, until the applicable conditions begin to contribute to the evaporation of the plasticizer.

Then, in operation (202), the dressing is placed in warm water to initiate pore formation. The resulting voids left by the pore-forming system lead to the appearance of a shell with interconnected pores. The size of the obtained pores depends on the size of the used particles of the blowing agent. Essentially, any method can be used to control the particle size of the pore-forming system, including, but not limited to, screening and centrifugation. In one embodiment, the pore-forming system is sieved through one or more screens to obtain particles of a certain size. Thus, the pore size can be minimally equal to the size that gives a sieve.

Typically, the pore size provided by the pore-forming system is about 5-1500 microns. In one embodiment, the pore size is from about 100 to 500 microns. In another example implementation, the pore size is from about 100 to 250 microns. Additionally, the amount of pore-forming system used and the particle size of the pore-forming system will control the percentage of porosity. In a preferred embodiment, the percentage of porosity is at least about 50%. In another preferred embodiment, the percentage of porosity is about 70%. In another preferred embodiment, the percentage of porosity is at least about 90%.

Then, in operation (203), microparticles are formed from a bioresorbable polymer, or, in one example, microspheres. Microspheres can be obtained in any way convenient for the artist. For example, a method for producing microspheres may be a spray method, as can be seen in US Pat. No. 6,238,705. In addition, a method for producing such polymer microspheres from an oil / water emulsion, for example, a method using an oil-in-water emulsion, or water-in-oil, or oil-in-oil, can be used as a production method. Microspheres can also be obtained by methods involving the use of an aqueous two-phase method, which was used to obtain polymer microspheres, for example, the method disclosed in the publication of Gehrke et al. (Proceed. Intern. Symp. Control Rel. Bioact. Material., 22, 145-146). Preferably, a method using an oil-in-water emulsion followed by evaporation is used to form the microspheres. In an oil-in-water emulsion process, at least one bioresorbable polymer is dissolved in a solvent to form a first mixture. The polymer mixture is then added to an aqueous solution, preferably containing a surfactant, and mixed vigorously. Then the solvent is evaporated, leaving the resulting microspheres.

Bioresorbable polymer microspheres can be any size that best suits the needs of the artist. While the microspheres are essentially spherical in shape, microparticles of other shapes can also be formed. The microparticles can be a rectangular parallelepiped, cylinder, rod, cube, have an irregular or any other shape. In addition, bioresorbable microparticles may contain tissue growth promoting or healing agents, for example, an antibacterial agent, an antiviral agent, a tissue growth promoting agent, a fibroblast growth factor, a transforming β-growth factor, or other chemically active agent. Additionally, tissue growth promoting or healing agents may be prepared synthetically or naturally, and may be a fragment, derivative or analog of a growth promoting or healing agent.

If the emulsion method is used to form microspheres, the diameter of the microspheres depends on the concentration of the polymer and on the intensity of mixing. The diameter of the microspheres can also be further controlled by using sieves to sift the microspheres. It is desirable that the diameter of the microspheres be such that the pores of the shell are smaller than the diameter of the microspheres. It is undesirable to have a diameter of microspheres smaller than the pore size in the shell, since then the microspheres will not be able to remain inside the shell. Preferably, the microspheres have a diameter in the range of about 20 to 800 microns, more preferably about 400 microns to 600 microns. For non-spherical microparticles, particles with similar sizes are preferred.

In the next step (204), the bioresorbable polymer in the form of a cylinder, i.e. the shell, is filled with bioresorbable microspheres. Screeds are formed on the shell at regular, repeating intervals to form a bandage in the form of a tow. The step (205) of forming the screeds can be carried out by twisting, using heat, a solvent, or the like. In general, forming screeds on the sheath reduces the diameter or width of the sheath in the screed area. This provides additional flexibility along the length of the shell. Because the sheath can easily be bent, folded, or otherwise manipulated due to the presence of screeds, the sheath can be easily adapted to fit the limits of the wound surface or tissue surface of any shape.

A third embodiment of the present invention is a method for producing a porous, bioresorbable dressing that can be placed in a wound of any size, shape or depth and which is able to fill the wound completely due to its configuration in the form of a tourniquet; in this method, the pore-forming system is activated in vivo by placing the dressing in contact with wound fluids, which may include interstitial fluid in the tissues or fluid that has escaped from the tissue or its capillaries on the wound surface. A method of manufacturing a bandage is illustrated in Fig.3. A dressing can be used to facilitate tissue growth and / or healing.

The method includes an operation (301) of forming a shell by applying one or more bioresorbable polymers and a pore-forming system. First, one or more bioresorbable polymers are dissolved in a suitable solvent. The type of solvent will depend on the biologically absorbable polymer (s) selected. Then, a pore-forming system is added to the bioresorbable polymer mixture. The pore-forming system can be used in stoichiometric amounts. You can also imagine that you can apply the pore-forming system is not in stoichiometric quantities. The polymer mixture is then sprayed, dipped, or poured onto a cylinder and the residual solvent is removed. Examples of solvent removal methods include, but are not limited to, evaporation, oven drying, vacuum drying, and the like. In one embodiment, the solvent is evaporated over a period of about 48 hours.

In an alternative embodiment, one or more plasticizers are added to the bioabsorbable polymer in the solvent. If one or more plasticizers are included in the polymer, the residual solvent can be removed in any way, for example, by drying in an oven or drying under vacuum, until the conditions applied begin to promote the evaporation of the plasticizer.

Then, in operation (302), microspheres of a bioresorbable polymer are formed. Bioresorbable microspheres can be obtained by any method convenient for the artist. Additionally, bioresorbable polymer microspheres may be sized to best suit the needs of the artist. While the microspheres are essentially spherical in shape, microparticles of other shapes can also be obtained. The microparticles can be in the form of a rectangular parallelepiped, cylinder, rod, cube, have an irregular or any other shape. Growth or healing stimulating agents, for example, an antibacterial agent, an antiviral agent, an agent for promoting cell growth, or any other chemically active agents, can also be incorporated into microparticles. In addition, growth promoting or healing agents can be prepared synthetically or naturally, and may be a fragment, derivative or analog of a growth promoting or healing agent.

If an emulsion is used to form the microspheres, the diameter of the microspheres depends on the concentration of the polymer and on the intensity of mixing. Microspheres can also be sieved through sieves to control their diameter. It is desirable that the diameter of the microspheres be such that the pores of the shell are smaller than the diameter of the microspheres. It is also desirable that the diameter of the microspheres be such that the location of the microspheres inside the shell does not interfere with the elasticity of the resulting dressing. Preferably, the microspheres have a diameter in the range of about 20 to 800 microns, more preferably about 400 microns to 600 microns. For non-spherical microparticles, particles of a similar size are preferred.

Then, in operation (303), a biodegradable polymer or shell formed in the form of a cylinder is filled with bioabsorbable microspheres. Screeds are formed on the shell at regular, repeating intervals to form a bandage in the form of a tow. The step (304) of forming the screeds on the shell can be carried out by bending, applying heat, a solvent, or the like. The dressing obtained by this method is also new, since the pore-forming system is activated in vivo when the dressing is placed in contact with wound fluids.

A fourth embodiment of the present invention is a method for producing a bioresorbable dressing that can be placed in a wound of any size, shape or depth and which is able to fill the wound completely due to its configuration in the form of a tourniquet; in this method, the dressing is made of extruded polymer. A method of manufacturing a bandage is illustrated in Fig.4. A dressing can be used to facilitate tissue growth and / or healing.

In operation (401), the bioresorbable polymer is dissolved in an appropriate solvent to form a non-solid mixture, for example a fluid or suspension, to form a mixture. Suitable polymers include, but are not limited to, the polymers disclosed in other embodiments of the present invention. In addition, the type of solvent used will depend on the biologically absorbable polymer (s) selected. In another embodiment, the bioabsorbable polymer is then mixed with one or more plasticizers.

Then, in operation (402), the resulting mixture is extruded into the precipitant for this polymer, so that the mixture is precipitated from the solution when the polymer comes into contact with the precipitant. In operation (403), the residual solvent is removed. Examples of solvent removal methods include, but are not limited to, evaporation, oven drying, vacuum drying, and the like. If one or more plasticizers are included in the mixture, oven drying or vacuum drying can also be used until the conditions applied begin to promote the evaporation of the plasticizer. If the polymer sheet contains undesirable bubbles or is uneven in thickness, then the obtained polymer can be subjected to compression molding with heating or compaction.

The obtained flat, two-dimensional sheet of biodegradable polymer in operation (404) is formed in the form of a three-dimensional shell by folding the sheet in the form of a cylinder and gluing the peripheral contacting edges. Bonding methods may include thermal welding, chemical bonding, physical crimping, or any other method that allows the edges to be tightly joined together to form a cylindrical shape. In addition, a two-dimensional sheet can be cut or act on it so as to better obtain a three-dimensional shell. For example, in one embodiment, the sheet may have two ends of such a shape that they are compatible when glued or welded. In another example implementation, a two-dimensional sheet is cut so that it has one edge having one or more cuts and protrusions, including a gripping or joining mechanism to bring its longitudinal edges together. A cylindrical shell is formed by inserting a portion of the protrusion into the cutout to obtain a cylindrical shell. In addition, the edges can be further joined by gluing.

Then, in operation (405), microspheres of a bioresorbable polymer are formed. Microspheres can be obtained in any way convenient for the artist. The diameter of the microspheres is preferably in the range of from about 20 to 800 microns, more preferably from about 400 to 600 microns.

Then, a biodegradable polymer or shell formed in the form of a cylinder is filled with bioresorbable microspheres in step (406). Screeds are formed on the shell at regular, repeating intervals with the formation of a bandage in the form of a tourniquet. The step (407) of forming the screeds can be carried out by bending, applying heat, a solvent or the like.

A fifth embodiment of the present invention is a method for producing a porous, bioresorbable dressing that can be placed in a wound of any size, shape or depth and which is able to completely fill the wound due to its configuration in the form of a tourniquet, and in which the dressing is made of extruded polymer . A method of manufacturing a bandage is illustrated in Fig.5. A dressing may be used to facilitate tissue growth and / or healing.

In operation (501), the bioresorbable polymer and the pore-forming system are dissolved in an appropriate solvent to form a non-solid mixture, such as a fluid or suspension, to form a mixture. Suitable polymers include, but are not limited to, the polymers disclosed in other embodiments of the present invention. In addition, the type of solvent used will depend on the biologically absorbable polymer (s) selected. In another embodiment, the bioabsorbable polymer is then mixed with one or more plasticizers.

Then, in step (502), the resulting mixture was extruded into a polymer precipitator so that the mixture precipitated from the solution in the form of a two-dimensional sheet. In operation (503), the residual precipitant is removed. Examples of solvent removal methods include, but are not limited to, evaporation, oven drying, vacuum drying, and the like. If one or more plasticizers are included in the mixture, oven drying or vacuum drying can also be used until the conditions used begin to promote the evaporation of the plasticizer. If the polymer sheet contains undesirable bubbles or has an inhomogeneous thickness, then the obtained polymer can also be subjected to compression molding with heating or compaction.

The resulting flat, two-dimensional biodegradable polymer sheet is then formed into a three-dimensional shell in steps (504) by folding the sheet in the shape of a cylinder and gluing peripheral contacting edges. Bonding methods may include thermal welding, chemical bonding, physical crimping, or any other method that allows the edges to be tightly joined together to form a cylindrical shape. In addition, a two-dimensional sheet can be cut or act on it so as to better obtain a three-dimensional shell. For example, in one embodiment, the sheet may have two ends cut so that they can be glued or welded together. In another example implementation, a two-dimensional sheet is cut so that it has one edge having one or more cutouts and protrusions constituting a gripping or joining mechanism that brings its longitudinal edges together. A cylindrical shell is formed by inserting a portion of the protrusion into the cutout to obtain a cylindrical shell. In addition, the edges can be further sealed by gluing.

Then, in operation (505), a cylindrical dressing is placed in water to react with a pore-forming system and create pores. The resulting voids remaining from the pore-forming system result in a shell with pores. The size of the obtained pores depends on the size of the used particles of the blowing agent. Essentially, means can be used to control the particle size of the blowing agent by, for example, sieving the particles through a sieve. Typically, pores created by a pore-forming system have a size of about 5 to 1,500 microns. In one embodiment, the pore size is from about 100 to 500 microns. In another example implementation, the pore size is from about 100 to 250 microns. Additionally, the amount of pore-forming system used and the particle size of the pore-forming system will control the percentage of porosity. In one preferred embodiment, the percentage of porosity is at least about 50%. In another preferred embodiment, the percentage of porosity is about 70%. In another preferred embodiment, the percentage of porosity is about 90%.

Then, in operation (506), microspheres of a bioresorbable polymer are formed. Microspheres can be obtained by any means convenient for the artist. The diameter of the microspheres is preferably in the range of from about 20 to 800 microns, more preferably from about 400 microns to 600 microns.

Then, the biodegradable polymer in the form of a cylinder, i.e., a shell, is filled with biodegradable microspheres in step (507). Screeds are formed on the shell at regular, repeating intervals to obtain a bandage in the form of a tow. The step (508) of forming the screeds on the shell can be carried out by bending, applying heat, a solvent, or the like.

A sixth embodiment of the present invention is a method and apparatus for applying a reduced pressure generation system to apply reduced pressure treatment of tissue on a wound surface, the system including a bioresorbable dressing including bioresorbable microspheres, as illustrated in FIG. 6. A dressing can be used to stimulate tissue growth and / or healing.

First, in step (601), a shell is formed by using one or more bioresorbable polymers. One or more bioresorbable polymers are dissolved in an appropriate solvent. The type of solvent used will depend on the biologically absorbable polymer (s) selected. The polymer mixture is then sprayed, dipped, or poured onto a cylinder and the residual solvent is removed. Examples of solvent removal methods include, but are not limited to, evaporation, oven drying, vacuum drying, and the like.

In an alternative embodiment, one or more plasticizers are added to the bioabsorbable polymer in the solvent. If one or more plasticizers are introduced into the polymer, the residual solvent can be removed in any way, for example, by drying in an oven or drying under vacuum, until the applicable conditions begin to promote the evaporation of the plasticizer.

Then, in operation (602), microspheres are formed from a bioresorbable polymer. Microspheres can be obtained in any way convenient for the artist. It is desirable that the diameter of the microspheres be such that filling the microspheres inside the shell does not interfere with the ductility of the resulting dressing. Preferably, the microspheres have a diameter in the range of about 20 to 800 microns, more preferably about 400 to 600 microns.

Then, in operation (603), the polymer microspheres are placed inside the shell. Screeds are formed on the shell at regular, repeating intervals to obtain a bandage in the form of a tow. The step (604) of forming the screeds on the shell can be carried out by bending, applying heat, a solvent, and the like. Then, the obtained dressing for surgery (605) is placed on the wound surface so that it fills the wound in shape and size. In an alternative embodiment, two or more dressings are weaved or intertwined to form a larger diameter dressing.

Then, in operation (606) in fluid connection with the wound surface, a device for treatment with reduced pressure is placed. In this case, the wound surface and the dressing are covered with a protective film made of a flexible substance. Preferably, the protective film is impermeable, and thus blocks or slows down the transfer of both liquid and gas. Preferably, the protective film is made of a material that allows diffusion of water vapor, but provides a tight seal over the wound surface when applying the treatment with reduced pressure. The protective film will be located above the wound surface and the dressing and go beyond the edges of the wound. A protective film is attached to the surface of the skin around the wound, for example, with adhesive material. At least one tube is placed under the protective film to create a reduced pressure that emerges from under the protective film. The reduced pressure tube may be made of any medical grade tube material, including, but not limited to, paralyne coated organosilicon or urethane materials. Additionally, the tube may be coated with agents to prevent the tube from sticking to the wound. For example, the tube may be coated with heparin, anticoagulants, anti-fibrogens, anti-adhesion agents, blood clot inhibitors, and hydrophilic substances. The tube for creating a reduced pressure is placed in fluid communication with a reduced pressure source, which preferably comprises a canister filter cartridge, securely placed under vacuum by means of a fluid connection with a reduced pressure source. Thus, in this embodiment, the dressing serves as a collector for distributing reduced pressure, facilitating the application of reduced pressure to the wound surface, the supply of fluids to the wound surface, or the removal of fluids from the wound surface.

Then in operation (607), a reduced pressure treatment is applied to the wound. It should be understood that the frequency of treatment with reduced pressure depends on the location of the body, the size and shape of the wound surface (specific dressing or dressing used) and the type of various agents applied to the surface, if used. In addition, depending on the organization of treatment, treatment with reduced pressure can be applied essentially continuously or cyclically, so that the pressure varies over time.

The unique configuration of the dressing described herein leads to the fact that the microparticles provide resistance to compression resulting from the application of reduced pressure treatment. This compression resistance transfers mechanical forces to the wound, which contributes to the formation of granulation tissue. Over time, a new tissue will grow in the space between the microparticles. In addition, granulation tissue replaces the bioresorbable polymer as it decomposes.

In another embodiment, one or more plasticizers are added to the bioabsorbable polymer in a solvent in step (601). If one or more plasticizers are included in the polymer, the residual solvent can be removed in any way, for example by drying in an oven or drying under vacuum, until the conditions used begin to promote the evaporation of the plasticizer.

In yet another embodiment, operation (601) further includes adding a pore-forming system to the bioresorbable polymer in the solvent. Thus, in operation (605) of placing a dressing on a wound surface, wound fluids can react with a pore-forming system to initiate pore formation in situ.

A seventh embodiment of the present invention is a method and apparatus for a reduced pressure delivery system used to treat tissues by applying reduced pressure to a wound surface, the system comprising a porous, bioabsorbable dressing including bioresorbable microspheres, as illustrated in FIG. 7.

A sheath in operation (701) is formed by using one or more bioresorbable polymers. One or more bioresorbable polymers and a pore-forming system are dissolved in an appropriate solvent. The type of solvent used will depend on the biologically absorbable polymer (s) selected. The polymer mixture is then sprayed, dipped, or poured onto the cylinder or inside the hollow cylinder so as to cover the surface, and the residual solvent is removed, for example, by evaporation, oven drying, vacuum drying, and the like. In another embodiment, one or more plasticizers are added to the bioabsorbable polymer in a solvent. If one or more plasticizers are introduced into the polymer, the method for removing residual solvent should not cause the plasticizer to vaporize.

Then, in operation (702), the cylindrical shell is placed in water so that it reacts with the pore-forming system. The resulting voids left by the pore-forming system result in a shell containing pores. The size of the obtained pores depends on the size of the used particles of the blowing agent. Essentially, means can be used to control the particle size of the blowing agent by using, for example, sieves for screening the particles. Typically, the pore size formed by the pore-forming system is from about 5 to 1500 microns. In one embodiment, the pore size is from about 100 to 500 microns. In another example implementation, the pore size is from about 100 to 250 microns. Additionally, the amount of pore-forming system used and the particle size of the pore-forming system will control the percentage of porosity. In one preferred embodiment, the percentage of porosity is at least about 50%. In another preferred embodiment, the percentage of porosity is about 70%. In another preferred embodiment, the percentage of porosity is at least about 90%.

Then, in operation (703), bioresorbable microspheres are formed. Microspheres can be obtained in any way convenient for the performer. It is desirable that the diameter of the microspheres be such that the placement of the microspheres inside the shell does not interfere with the flexibility of the resulting dressing. Additionally, the diameter of the microspheres should be larger than the diameter of the pores inside the shell formed by the pore-forming system. Preferably, the microspheres have a diameter in the range of about 20 to 800 microns, more preferably about 200 microns to 600 microns.

Then, in operation (704), the polymer microspheres are placed inside the shell. In operation (705), the couplers are formed into a cylindrical shell at regular intervals. The means for forming the screeds may include, but is not limited to, bending the sheath, using heat, solvent, or the like to form a bandage. Then, in operation (706), the obtained dressing is placed in the wound so that it fills the wound in shape and size. In an alternative embodiment, two or more dressings are weaved or intertwined to form a larger diameter dressing.

Then, the device for conducting treatment with reduced pressure in operations (707) is placed in a fluidic connection with the wound surface. At this point, the wound surface and dressing are covered with a protective film made of an impermeable substance that is flexible. A protective film covers the wound surface and the dressing and extends beyond the edges of the wound, and preferably it is attached to the skin surface around the circumference of the wound. At least one tube is placed under the protective film to create a reduced pressure that emerges from under the protective film. The tube for creating a reduced pressure is placed in fluid communication with a reduced pressure source, which preferably includes a filter cartridge that is securely placed under vacuum by means of a fluid connection with a reduced pressure source. Thus, in this embodiment, the dressing serves as a manifold for distributing the reduced pressure.

Then, in operation (708), a reduced pressure treatment is applied to the wound. The unique configuration of the dressing described herein leads to the fact that the microparticles provide resistance to compression resulting from the use of reduced pressure treatment. This compression resistance transfers mechanical forces to the wound, which contributes to the formation of granulation tissue. Over time, the new tissue will grow into the voids between the microparticles. Subsequently, granulation tissue replaces the bioresorbable polymer as it decomposes.

An eighth embodiment is a method and apparatus for stimulating the growth of new tissue on a wound surface by applying a dressing of a bioabsorbable polymer including bioabsorbable microspheres that are located inside the bioabsorbable membrane, as illustrated in FIG. In this case, the dressing (801), made by the methods disclosed in the present description and illustrated in Figs. 1-5, 10A, 10B and 10C, is placed within the wound surface (802), folding the dressing (801) so that it fills wound surface (802) in shape, size and depth.

Then, the wound surface (802) and the dressing (801) are covered with a distribution manifold (803). A protective film (804) is placed over the wound surface (802), the dressing (801) and the distribution manifold (803), which extends beyond the edges of the wound surface, where it is then attached to the skin surface around the wound perimeter, for example, with glue. Preferably, the protective film (804) is made of an impermeable substance that is flexible and allows diffusion of water vapor, but provides an airtight coating.

The distribution manifold (803) includes at least one tube (805) to create a reduced pressure, which is in fluid communication with the manifold (803). Inside the distribution manifold, the tube (805) is perforated to create reduced pressure to form one or more holes. Outside the dispensing manifold, the tube (805) to create a reduced pressure is not perforated and leaves the dressing (801) and from under the protective film (804). The reduced pressure tube (805) can be made of any medical grade tube material, including, but not limited to, paralyzed silicone or urethane material and coated with agents to prevent the tube (805) from sticking to the wound surface .

The tube (805) for creating a reduced pressure is placed in liquid connection with a source (806) of reduced pressure, which preferably includes a container (806) for collecting liquid, safely placed under vacuum by means of a liquid connection with a source of reduced pressure. Thus, when you turn on the source (806) of reduced pressure on the wound surface (802) serves reduced pressure. When applying reduced pressure, the protective film (804) is pressed and corresponds to the surface of the distribution manifold (803), which applies pressure to the dressing (801), mechanically compressing the dressing (801) and pressing the dressing (801) into the wound surface (802). In addition, reduced pressure can pump out wound fluids present on the wound surface (802) through a distribution manifold (803) and a tube (805) for supplying reduced pressure to a container (806) for collecting fluid, thereby preventing fluids from entering the source itself (807) reduced pressure. Thus, in this embodiment, the distribution manifold serves to distribute the reduced pressure.

In one embodiment, the system and method of FIG. 8 can also be used with a bioabsorbable dressing in the form of a tow, including bioabsorbable microspheres, where the shell has no pores.

In another example implementation, the system and method of FIG. 8 is applied with a dressing that includes a pore sheath. In this case, the shell is formed of bioresorbable polymers and a pore-forming system, and the shell is brought into contact with a liquid that reacts with the pore-forming agent in the shell, creating pores. Then the porous membrane is filled with bioresorbable microparticles, screeds are formed on the membrane at regular, repeating intervals to form a bandage in the form of a tourniquet, and then placed within the wound surface.

In yet another embodiment, the system and method of FIG. 8 is applied with a sheath that contains a pore-forming system, but this pore-forming system is not activated before the dressing is placed within the wound surface. In this embodiment, the pore-forming system within the dressing membrane reacts with wound fluids, thereby forming pores in the membrane in situ.

An example configuration of a porous, bioresorbable dressing comprising bioresorbable microparticles is shown in FIG. 9. The bandage sheath (901) is made of a biodegradable polymer and preferably includes a plasticizer. Shell pores (902) are formed by using a pore-forming system. The shell (901) is filled with bioresorbable polymer microspheres (903), which can be obtained by any method convenient for the performer. The diameter of the microspheres (903) should be larger than the pore diameter (902) inside the shell. In addition, the diameter and number of microspheres used will lead to a change in the void space (904) between the microspheres. The void space is important because new tissue can penetrate this void space before the bioabsorbable microspheres collapse. Additionally, the diameter and number of microspheres used must be such that the resulting dressing is flexible enough to be rolled up on the wound surface.

Another example implementation of the present invention is the use of a mold for forming a bioresorbable dressing, including bioresorbable microparticles; this form is illustrated in FIG. 10A. First, a two-dimensional film of a bioresorbable polymer is formed. Two-dimensional film can be formed by any means. For example, a bioresorbable polymer can be dissolved in an appropriate solvent and then sprayed or poured into a two-dimensional sheet form, where the residual solvent is removed. Alternatively, the bioresorbable polymer can be dissolved in an appropriate solvent and then extruded into a precipitant. Further, the obtained bioresorbable polymer film can be heated pressed or compressed to obtain a film of the desired thickness. In order to make the film more malleable, one or more plasticizers can be added to the bioresorbable polymer in the solvent.

Then, the obtained first film (1003) from a bioresorbable polymer is placed in the mold (1001). The mold is a three-dimensional structure containing holes or voids placed on one surface of the mold. An alternative view of the wells in the mold is shown in FIG. 10 B. The first bioabsorbable polymer film (1003) is placed on the mold so that the film is pressed into the holes (1002) or voids and in contact with their inner surface.

Then microspheres (1004) are formed from a bioresorbable polymer. Microspheres can be obtained in any way convenient for the artist. For example, a method for producing microspheres may be a spraying method, a method using an oil-in-water, water-in-oil, oil-in-oil emulsion, and the like. Preferably, the resulting microspheres have a diameter in the range of about 20 to 800 microns, more preferably about 400 microns to 600 microns.

Then, the microspheres of the bioresorbable polymer are placed in the wells (1002), and on top of the microspheres (1004) and the first film (1003) of the bioresorbable polymer, a second film (1005) of the bioresorbable polymer is placed. Thus, the first bioresorbable polymer film (1003) and the bioresorbable polymer film (1005) are in contact with each other in the (1006) zone around the wells. A second mold (1007) is placed on top of the second bioresorbable polymer film (1005), and both molds, mold (1001) and mold (1007) are pressed against each other to seal the microspheres inside the wells, thereby obtaining a bioabsorbable dressing from the bonded capsules.

Additionally, in an alternative embodiment, in order to facilitate adhesion of the bioabsorbable capsules, a bioabsorbable suture can be used. Thus, the first form (1001) will contain a first bioabsorbable polymer film (1003) placed in wells (1002), where the wells (1002) are filled with microspheres (1004). Then, a bioresorbable suture material is applied across the mold so that this suture material lies on top of the holes (1002). On top of the suture material, microspheres (1004) and the first film (1003) of bioabsorbable material, a second film (1005) of bioabsorbable polymer is placed. Then, holding the second film (1005) of the bioresorbable polymer in place to prevent the microspheres (1004) from falling out, the first form can be turned over to the second form (1007). Then, the two forms, the mold (1001) and the mold (1007) are pressed against each other when heated to seal the microspheres inside the wells, thereby obtaining biologically absorbable capsules interlocked with each other. In addition, it is contemplated that it is also possible to arrange two shapes, shape (1001) and shape (1007), so as to lay suture material by filling the hollow channel (1008) located between the holes (1002), as shown in another image of the shape (1001) ) on Figs. Thus, in this other image, the region (1006) between the wells (1002) can be provided with a hollow channel (1008) such that when the first mold (1001) and the second mold (1007) are pressed together when heated, the suture is not damaged and not flattened.

In another alternative embodiment, the second form (1007) also includes a third bioabsorbable polymer film placed inside the wells of the second form and filled with microspheres of the bioabsorbable polymer. Thus, the first form (1001) will include a first bioabsorbable polymer film (1003) placed inside the wells (1002), wells (1002) filled with microspheres (1004), and a second bioabsorbable polymer film (1005) placed over microspheres (1004) and the first film (1003) of a bioresorbable polymer. Then you can hold in place the second film (1005) of the bioresorbable polymer to prevent the loss of microspheres (1004), and turn the first form to the second form (1001). Then the two forms, mold (1001) and mold (1007), are pressed together when heated to seal the microspheres inside the wells, thereby obtaining a bandage from cohesive, bioresorbable capsules.

Additionally, in yet another alternative embodiment, the bioresorbable polymer films further include a pore-forming system. Essentially, a bioresorbable polymer film can be placed in water so that it reacts with the pore-forming system to form pores. This can be done before bioresorbable films are used to form cohesive capsules by using the mold of FIG. 10A-C. Otherwise, the reaction of the pore-forming system and the creation of pores can be carried out in situ when a dressing from adhered biologically absorbable capsules comes into contact with wound fluids. The size of the obtained pores depends on the size of the used particles of the blowing agent. Essentially, means can be used to control the particle size of the blowing agent by using, for example, sieving the particles through a sieve before adding the blowing agent particles to the bioresorbable polymer. Typically, the pore size provided by the pore-forming system is about 5 to 1,500 microns. In one example, the pore size is from about 100 to 500 microns. In another example implementation, the pore size is from about 100 to 250 microns. Additionally, the amount of pore-forming system used and the particle size of the pore-forming system will control the percentage of porosity. In one preferred embodiment, the percentage of porosity is at least about 50%. In another preferred embodiment, the percentage of porosity is about 70%. In another preferred embodiment, the percentage of porosity is at least about 90%.

It is desirable that the diameter of the microspheres be such that the pores of the shell are smaller than the diameter of the microspheres. It is undesirable to have a diameter of the microspheres smaller than the pore size in the shell, since the microspheres could not remain inside the shell.

Thus, the use of the molds of FIGS. 10A-10C results in the dressing illustrated in FIG. 11. In this case, the bioresorbable capsules (1101) are adhered to each other by the bioresorbable material (1102), formed either by the use of the bioresorbable suture material or by pressing films of the bioresorbable polymer. Thus, each capsule (1101) consists of bioresorbable microparticles (1104) enclosed in a film (1103) of a bioresorbable polymer.

The dressing of FIG. 11 can be used in the treatment of low blood pressure. This dressing has a new advantage in that it can be rolled up on the wound surface and fill the wound surface in shape, size and depth. When applying the treatment with reduced pressure, the capsules (1101) are pressed into the wound surface, which contributes to granulation. Due to the presence of air pockets between the capsules, the dressing itself can be used to distribute reduced pressure during treatment. Alternatively, the bandage of FIG. 11 may be used with a distribution manifold.

Another example implementation of the present invention relates to a kit for tissue growth, which is proposed to stimulate the growth of new tissue on the wound surface. The tissue growth kit includes a biologically absorbable dressing in the form of a tow, including bioresorbable microparticles, a collector adapted to come in contact with the dressing, and a device for generating reduced pressure.

Additionally, in a final embodiment of the present invention, a bioresorbable dressing can be formed including bioresorbable microparticles where a shell or film of a bioresorbable polymer is not used. In this embodiment, microparticles are formed and then dried. The microparticles are placed in a cylindrical shape, which is not made of bioresorbable material. Between the microparticles in a dry or hydrated state, cross-linking is formed by any means, including, but not limited to, photo-bonding, chemical bonding, thermal bonding, and the like. The mold is removed, and the resulting cross-linked microparticles form a cylindrical dressing, including microparticles. The dressing can then be used to treat low blood pressure.

While many of the implementation examples described herein include microspheres having a substantially spherical shape, it should be recognized that microspheres can be replaced with microparticles having other shapes. For example, microparticles of other shapes can also be formed. The microparticles can be a rectangular parallelepiped, cylinder, rod, cube, have an irregular or other shape.

It should also be understood that any biologically absorbable film can be used as a shell for microparticles. Examples may include, without limitation, woven, non-woven or knitted materials or sheets. In general, it is desirable that these materials be flexible and porous, and also capable of containing microparticles.

From the foregoing, it is obvious that the invention has significant advantages. While the invention is shown in only a few of its forms, it is not at all limited to them and allows various changes and modifications without departing from its essence.

Claims (25)

1. A method of obtaining a bioresorbable dressing, including bioresorbable microparticles, where the specified method includes:
I) the formation of the shell, essentially cylindrical in shape, including a pore-forming system, through the following stages:
a) dissolving one or more bioresorbable polymers and a pore-forming system in a solvent to form a mixture;
b) applying said mixture to a cylinder mold; and
c) removing said solvent;
II) the placement of microparticles, including at least one bioresorbable polymer, inside this shell; and
III) the formation on the shell of screeds at repeated intervals. 2. The method according to claim 1, in which the mixture further includes a plasticizer. 3. The method according to claim 1, further comprising manufacturing said microparticles using a method with an oil-in-water emulsion. 4. The method according to claim 1, in which the size of the microparticles is from about 400 to 600 microns. 5. The method according to claim 1, wherein said pore-forming system is sodium carbonate and acid. 6. The method according to claim 1, in which the pore-forming system is a salt. 7. The method according to claim 1, wherein said one or more bioresorbable polymers are a PLA: PCL copolymer. 8. The method according to claim 7, in which the ratio of PLA: PCL is approximately 90:10. 9. The method according to claim 7, in which the ratio of PLA: PCL is approximately 80:20. 10. The method according to claim 1, further comprising the step of reacting said pore-forming system with a liquid to form pores within the shell. 11. The method of claim 10, wherein said pores formed inside the shell result in porosity of said shell, which is more than 70%. 12. The method according to claim 10, in which the diameter of these pores is from about 100 to 500 microns. 13. A method of obtaining a bioresorbable dressing, including bioresorbable microspheres; where the specified method includes:
I) the manufacture of the shell, including the pore-forming system, through the following stages:
a) dissolving one or more bioresorbable polymers and a pore-forming system in a solvent to form a mixture;
b) extruding said mixture into a precipitant to form a two-dimensional sheet;
c) removing said solvent;
d) folding sheet in the form of a cylinder and gluing the opposite contacting edges;
II) the manufacture of microspheres comprising at least one bioresorbable polymer;
III) the placement of these microspheres made in stage (II), inside the shell made in stage (I);
Iv) screed sheath at regular, repeating intervals. 14. The method according to item 13, in which the specified mixture further includes a plasticizer. 15. The method according to item 13, in which the diameter of these microspheres is from about 400 to 600 microns. 16. The method of claim 13, wherein said pore-forming system is sodium carbonate and acid. 17. The method according to item 13, in which the specified pore-forming system is a salt. 18. The method according to item 13, in which these one or more bioresorbable polymers are a copolymer of PLA: PCL with a ratio of PLA: PCL in the range from about 90:10 to 70:30. 19. A method of stimulating new tissue growth and / or wound healing on a wound surface, including:
the manufacture of a dressing comprising a shell and microspheres, where the specified shell includes one or more bioresorbable polymers and a pore-forming system, these microspheres include one or more bioresorbable polymers, and
these microspheres are inside the shell;
bringing the dressing in contact with the liquid to form pores by the pore-forming system;
placing the dressing on the wound surface, so that the dressing is in contact with the wound surface;
covering the dressing with a protective film and
the creation of reduced pressure on the wound surface through the dressing. 20. The method according to claim 19, wherein said mixture further comprises a plasticizer. 21. The method according to claim 19, in which the diameter of these microspheres is from about 400 to 600 microns. 22. The method according to claim 19, in which the diameter of these pores is from about 100 microns to 500 microns. 23. A method of accelerating the growth of new tissue and / or healing of wounds on the wound surface; said method includes:
the manufacture of dressings, including the shell and microparticles,
in which the specified shell includes one or more bioresorbable polymers and a pore-forming system,
in which these microparticles are formed from one or more bioresorbable polymers, and
in which these microparticles are inside the shell; placing the dressing on the wound surface so that the dressing is in contact with the wound surface;
placing the distribution manifold on the dressing so that the distribution collector is in contact with the dressing; covering the dressing with a protective film; and
creation of reduced pressure on the wound surface through the dressing and distribution manifold. 24. The method of claim 23, wherein said pore-forming system is activated in situ by wound fluids to initiate pore formation. 25. A system for applying tissue treatment by reduced pressure on the wound surface, including:
bioresorbable dressing, including a porous membrane and bioresorbable microparticles;
distribution manifold;
protective film;
source of reduced pressure and
tube for transmitting reduced pressure.

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