DE102013111322A1 - Process for the preparation of hydrocolloid sponges - Google Patents

Abstract

The invention relates to a wound healing material and its production.

Description

The invention relates to a wound and brand implant comprising an antibacterial, bioabsorbent and healing hydrocolloid.

Field of the invention

The present invention relates to a wound and fire implant (sponge) which promotes recovery and prevents bacterial infections.

General information about the invention

Process for Producing the Hydrocolloid Gelatin has been known for a long time. There are several techniques for producing coating films and foams as biomaterials. However, the areas of application and the effect of protecting the wound from environmental influences are the same.

The skin is a large sensory organ that interacts with the environment and sends signals to the brain about touch, pain, vibration, and position.

The skin has several layers, the most important are the dermis and the epidermis.

The epidermis is the visible part. It represents the outer layer of the skin. It is very active in the formation of new skin cells and their slow desquamation. There are different types of epidermal cells. The damage can lead to cracks, defects and wounds in the skin. The skin can also be damaged by injuries of various kinds.

The types of wound are marked as follows:
Inflammation; external (on the surface) wounds and abrasions; deep abrasions (cuts); Perforationswunden; Bite wounds from humans and animals; Decubital ulcers (due to bedsores).

The appropriate wound care is necessary to prevent infections and the development of possible accompanying wounds and to support the recovery of the skin. Another goal is to minimize scar formation during healing.

The process of healing a wound is very complicated. In a normal skin, the epidermis (the outer layer) and the dermis (the inner or the deep layer) are in a kind of closed state to the environment. It has a protective barrier and is stable.

Once the barrier is damaged, the normal (physiological) recovery process of the wound begins.

• (1) Hämostasis (Blutstillung, wird von einigen Forschern nicht als eine Phase akzeptiert)
• (2) Entzündung,
• (3) Proliferation, und
• (4) Neugestaltung.

The classical model has four phases:

• (1) haemostasis (hemostasis, not accepted as a phase by some researchers)
• (2) inflammation,
• (3) proliferation, and
• (4) redesign.

After skin injury, there are a lot of complex biochemical events to repair the damage.

After the trauma, platelets (thrombocytes) are formed in a few minutes at the site of the wound for fibrin blood clotting. This clotting prevents active hemorrhage (hemostasis).

In the inflammatory phase, the foreign bodies are removed.

In the proliferative phase, the factors that cause the cells to divide and migrate are released.

The proliferative phase is characterized by angiogenesis, collagen clustering, granulation tissue formation, epithelization and wound contraction.

In angiogenesis, the new blood vessels are formed by the vein cells of the endothelium.

During fibroplasia and the formation of granulation tissue, the fibroblasts, collagen and fibronectin create a new extracellular matrix (ECM).

At the same time the epithelialization of the epidermis takes place. The epithelial cells become productive and prepare a layer for the new tissue.

There is a stenosis and the wound becomes smaller due to the movement of the fibroblasts. This is done by contracting the fibroblasts at the wound edges, in a mechanism similar to that of smooth muscle cells.

When the cells have completed their tasks, those who are no longer used die (apoptosis).

During the maturation phase and redesign, the collagen re-forms and accelerates along the voltage lines. The cells that are no longer used die off (apoptosis).

This process is complicated and also vulnerable. It is possible that this forms a non-healing, chronic wound. The formation of a chronic wound is also due to disorders of the veins (blood vessels) and arteries (arteries), by age and by certain diseases, such. As diabetes and infections, influenced.

• • Der Verband, der die Feuchtigkeit in der Wunde regeln soll und dadurch dafür sorgt, dass die Wunde trocken oder feucht bleibt. 'Aquacel' kann als ein Beispiel für einen Verband angegeben werden, der die Feuchtigkeit erhält. 'Aquacel' wird bei lückenhaften, tiefen Verbrennungen benutzt und ist eine Hydrofiber.
• • Der Verband, der die Wunde vor Infektionen schützt.
• • Der Verband, der Ablagerungen entfernt.
• • Der Verband, der für geeignete pH-Werte und Temperaturen sorgt, um die Genesung auszulösen.

In the past, a piece of cloth was used as dressing material. However, it is also known that items such as cobwebs, leaves and honey were used in the past as a dressing. However, modern dressings may also be made from tulle (may have been impregnated with a material to be sterile and to speed recovery), a coating film, a gel, a foam, a hydrocolloid, alginate, a hydrogel, a polysaccharide cream, Granules and pearl-shaped particles exist. Mostly, the absorbent gauze bandages on the surface have a film layer that prevents adhesion. The bandages used in surgery can be soaked in antiseptic chemicals. The first bandages used antiseptic chemicals such as "boracic lint" or medical castor. Various associations are used for various purposes, as indicated below.

• • The dressing designed to regulate the moisture in the wound, thereby keeping the wound dry or moist. 'Aquacel' can be given as an example of a dressing that will retain moisture. 'Aquacel' is used in incomplete, deep burns and is a hydrofiber.
• • The dressing that protects the wound from infection.
• • The dressing that removes deposits.
• • The bandage that provides appropriate pH and temperature to induce recovery.

Bandages made of materials such as plastic or latex that are moisture repellent are used to better absorb local medicines from the wound.

The most useful wound care materials today are hydrocolloids such as gelatin. Here are some examples of patents or patent applications for plasters: sponge hydrocolloids ( WO 94/17137 ), oxygen diffusion level therapeutic diffusion hydrocolloid patches ( US 2012/0059301 A1 ), therapeutic diffusion hydrocolloid patches ( US 2011/0257617 A1 ), Hydrocolloid composition ( WO 2007/048193 ), Hydrocolloids materials used for wound healing ( WO 2004/080500 A1 ); a sticky layer containing various hydrocolloid components ( US 8,147,469 B2 ); Use and production process of a material which is rapidly wettable and contains a hydrocolloid ( US 2011/0071227 A1 ); Compositions which contain sucralose and produce a coating film ( US 2003/0108607 ); a hydrocolloid bandage with calendar ( US 2002/0106400 A1 ), Silk material systems ( WO 2011 / 008842A3 ); antibiotic dressing for the treatment of wounds ( US 2009/0297588 A1 ).

Brief explanation of the invention

In a first aspect, the invention relates to a method of making hydrocolloid sponges characterized by adding active ingredients to a combination of a silk peptide and a hydrocolloid polymeric material.

In a second aspect, the invention relates to the use of a sponge for wound covering produced by a method according to the first aspect.

In a third aspect, the invention relates to a sponge made by a method according to the first aspect.

The purpose of this invention is to provide an effective, combined care material for wounds and burns. The infection is the biggest problem in the care of the wound. As a solution to this, a plaster with antibacterial content was developed. Many wound dressings have an antibacterial effect due to their antibacterial additives. However, most of the antibacterial agents cause cytotoxicity. These products, because of their cytotoxic effect, delay the healing of the wound while protecting it from infection. When a product containing a silk peptide was used, its antibacterial properties were discovered. The second problem is the delayed or non-occurring healing of the wound. Sometimes it is necessary to support cell activity. This is especially important for chronic wounds. When cell activity is assisted in acute wounds, less scar tissue is formed. Here, an epidermal growth factor was added, supporting this property.

The extreme formation of exudate causes the pH of the product to decrease, which is undesirable. Since all hydrocolloid sponge dressings have the property of absorbing the exudate, this effect is also achieved in the present case. However, this leads because of the antibacterial and antiseptic properties, causing the wound to dry out.

According to the invention, ceramides are added to prevent dehydration. Ceramides refer to a subgroup of sphingolipids which belongs to the lipids. A ceramide consists of a sphingosine molecule bound to a fatty acid through an amide bond. The ceramides occur frequently in the cell membrane. On the one hand they form the lipid components of sphingomyelin and on the other hand they form the main lipids between two layers. The ceramides, which are in the bilayer cell layer, and other sphingolipids have long been understood as structural elements only. Now, this proves not quite right. Ceramides can develop on existing birthmarks. They are therefore actually a birthmark. Among the known tasks of ceramides is to regulate differentiation, proliferation, systematic necrosis (PCD) and apoptosis (type 1 PCD). Ceramides added to the patches protect the wound from dehydration and reduce its itching. Their presence is also helpful in regeneration.

The last point is the production process. Cocamidopropylbetaine is added to the mixture in an amount of 1 to 3% to provide resistance and to cause foaming. Cocamidopropylbetaine (CAPB) is an artificial surface moisturizer made from coconut oil and dimethylaminopropylamine. Cocamidopropyl betaine is a chemical zwitterion compound that has both an ammonium cation and a carboxylate. Cocamidopropyl betaine is available as a viscous, slightly yellow surface moisturizing solution used in shampoos, soaps and such cosmetic articles. It is also used in cosmetics as emulsifier and stabilizer. It also serves to reduce irritation. Cocamidopropyl betaines are also used as an antiseptic in hair products. Cocamidopropylbetaine is a derivative of cocamide and glycine betaine (a type of betaine). Cocamidopropylbetaine is a medium surface moisturizer that does not irritate the skin or mucous membranes. In the context of the invention, the substance cocamidopropyl betaine was used in order to simplify the production. In addition, the antiseptic character of the product is enhanced.

Figure Legend

The 1 to 4 show the following:

1 A healing, antibacterial, absorbent and hydrocolloid-based implant for wounds and burns.

2 : Sponge comprising gelatin and a silk peptide.

3 : Sponge comprising a silk peptide, gelatin and the growth factor EGF (Epidermal Growth Factor).

4 : Sponge that has ceramides.

Detailed description of the invention

The invention relates to an antibacterial implant for wounds and burns, which, due to the composition, stimulates healing. In particular, the implant can be used as a tissue-supporting and repairing material and as a skin-coating material. This is due to the hydrocolloids, the coating film structure and the addition of a bioactive chemical material. Materials used in medical applications can be of natural or artificial origin and occur in various shapes and structures. Some materials that have a natural polymeric structure can be modified by various chemical materials to increase stability. The synthetically synthesized polymeric materials are durable materials. It is important that the material or substance interact with the biological environment. It may happen that the materials themselves or the additives added during the synthesis and processing lead to a foreign body reaction and trigger unwanted effects. Here, the undamaged structures, according to the self-defense mechanism of the body, surrounded by soft tissue and encapsulated. It is therefore important that the materials used in the medical application interact with the biological environment and have no toxic effect.

Biodegradable materials are preferred in the following medical fields: wound dressing, wound area filler, skin graft, surgical thread, long-term medication systems as a temporary prosthetic material and / or as a carrier material (long-term drug systems as a temporary prosthetic and / or as a support material). It is important that biodegradable materials are physically homogeneous. The material must have sufficient stability and processing options. As the tissue evolves over time, the material / implant used must degrade, have no side effect, and be completely absorbed by the body. The hydrocolloids allow interaction with water and reduce diffusion. Characteristic is the Dissolution of neutral hydrocolloids in water. Hydration kinetics depend on more than one factor. The mixture of hydrocolloids causes the hydration, the viscosity and the expansion of the whole composition.

In a first aspect, the invention relates to a method of making hydrocolloid sponges characterized by adding active ingredients to a combination of a silk peptide and a hydrocolloid polymeric material.

The hydrocolloid polymeric material may be a natural polymeric material or an artificial polymeric material. The natural or artificial polymeric material can be modified by various chemical materials to increase stability.

The hydrocolloid polymer material is preferably gelatin.

The active ingredients preferably include the growth factors EGF (Epidermal Growth Factor), FGF (Fibroblast Growth Factor) and / or IGF (Insulin-like Growth Factor).

In one embodiment of the process, water, preferably distilled water, may be added.

In one embodiment of the method, an antiseptic, preferably the antiseptic propyl betaine, may be added. An antiseptic is a chemical used in medicine to prevent wound infection and, subsequently, sepsis.

In a further embodiment of the method, substances for the protection of cells (eg skin cells, in particular cells of the epidermis), preferably ceramides, can be added. The ceramides have the advantages listed above. In particular, ceramides can prevent the drying out of the wound surface.

In a further embodiment of the process, a solvent, preferably a liquid solvent, may be added.

In a particular embodiment of the process, a foam conveyor, preferably the foam conveyor cocoamidopropylbetaine (CAPB), may be added.

As cross-linking agent, glutaraldehyde can be added. The hydrocolloid sponge, which has a combination of a hydrocolloid polymeric material and a silk peptide, can be prepared as follows: First, the hydrocolloid (eg, gelatin) is frozen. Then a silk peptide and become active ingredients, eg. Growth factors. The ingredients are solved. Glutaraldehyde can be used as cross-linking agent. The formation of a foamy material can be promoted by the addition of Cocoamidopropylbetaine. To process the ceramide molecules, silk protein was used in the present invention. Ceramide molecules bind the water to the skin. Silk is well-tolerated with protein-soaked gelatin. If synthetic hydrocolloids are used, the ceramide molecules should be processed with dodecane-ethanol at room temperature (2.98 vol.).

The growth factors that are in the bioactive structure protect the implant from absorption too quickly and support cell growth in terms of tissue regeneration.

In this invention, the growth factors are embedded in the hydrocolloid structure (e.g., gelatin).

Yet another important issue in this invention is the foaming process. Environmental conditions, quality of joints, temperature, etc. can affect the quality of production. To reduce the risk, cocoamidopropylbetaine can be added as a kind of foam stabilizer. The presence of 1 to 3% cocoamidopropyl betaine improves the quality of the foam and increases the amount of bubbles.

In a second aspect, the invention relates to the use of a sponge for wound covering produced by a method according to the first aspect.

In a third aspect, the invention relates to a sponge made by a method according to the first aspect. This sponge has a combination of a silk peptide and a hydrocolloid polymer comprising active ingredients.

The combination of a silk peptide and a hydrocolloid polymer material may be layered. For example, the hydrocolloid sponge may comprise a layer of silk peptide and a layer of hydrocolloid polymeric material.

The active ingredients may be part of the silk peptide layer and / or part of the hydrocolloid polymeric material layer. In addition, a layer or both layers ceramides include. In a particular embodiment of the invention, the layer of silk peptide may include ceramides and / or the hydrocolloid sponge layer may contain growth factors, such as EGF (Epidermal Growth Factor) (see, for example 1 ).

Individual hydrocolloid sponges may also be combined together to generate further layered materials having different properties. For example, a hydrocolloid sponge having a combination of silk peptide and gelatin and additionally comprising the growth factor EGF may be combined with a hydrocolloid sponge having a combination of silk peptide and gelatin and also comprising ceramides.

The sponge can serve as an implant for wounds, especially burns.

The hydrocolloid structures produced and the materials contained therein as well as examples of bioactive materials are described below.

experiments

• Pattern 1: sponge comprising silk peptide and gelatin.

2 grams of gelatin and 2 grams of silk peptide are dissolved in 100 ml of distilled water. The mixing takes place at a rotational speed of 2000 rpm (revolutions per minute). The upper layer of the solution is removed and frozen in nitrogen. The frozen material is dried by dry freezing technique. The material produced is a very soft material which, due to its property, can rapidly degenerate in porous and damp conditions.

• Pattern 2: Sponge comprising silk peptide, gelatin and the growth factor EGF (Epidermal Growth Factor).

• Muster 3: Hydrokolloidschwämme, die Seidenpeptid und Ceramide umfassen.

2 grams of gelatin and 2 grams of silk peptide are dissolved in 100 ml of distilled water. The mixing is done by means of a mixer at a rotational speed of 2000 rpm. To increase the stability of the sponges, 1 ml of a cross-linking agent is added (eg 0.1-5% glutaraldehyde). Subsequently, the stirring is continued. The surface-forming layer is removed and placed in a container cooled in liquid nitrogen. In this step, 50 μg of EGF and 50 μl of heparin are added to the mixture. It is cooled in liquid nitrogen. The frozen material is dried by means of dry-freezing technology ( 3 ).

• Pattern 3: Hydrocolloid sponges comprising silk peptide and ceramides.

• Muster 4: Im Anschluss an die Ceramide und an das Seidenpeptid wird dem Hydrocolloidmaterial Cocoamidopropylbetain zugesetzt, um die Schaummenge zu erhöhen.

The ceramides are added to the silk peptide in the ratio of 1 to 2 (1: 2). The mixture is kept in the refrigerator for 2 days. The hydrocolloid material containing enough silk peptide + ceramide is diluted with distilled water (2: 100). The mixture is stirred at a rotation speed of 2000 rpm. To the mixture is added 1 ml of a cross-linking agent (eg 0.1-5% glutaraldehyde). It is placed on the mixture explained in the second pattern. The mixture is cooled by liquid nitrogen and dried by dry-freezing technique.

• Pattern 4: Following the ceramides and the silk peptide, cocamidopropyl betaine is added to the hydrocolloid material to increase the amount of foam.

The ceramides are added to the silk peptide in the ratio of 1 to 2 (1: 2). The mixture is kept in the refrigerator for 2 days. The hydrocolloid material containing enough silk + ceramides is diluted with distilled water (2: 100). The mixture is stirred at a rotation speed of 2000 rpm. To the mixture is added 1 ml of cross-linking agent (0.1-5% glutaraldehyde).

Cocoamidopropylbetaine (eg 43%) and / or propylbetaine (eg 1-3%) are added in the last 10 minutes. If desired, glycerol may be added as softener.

Summary explanation of the invention

This invention relates to a wound healing material and its design. Most products on the market are either antibacterial or promote healing. In the product according to the invention, a combined structure was conceived. Sericin (component of the silk peptide) which has a strong antibacterial activity, the ceramide molecule, which has a superior effect on cell activity, and the growth factors were used together. The structure combined in this way has the property of protecting and healing the wound.

Cocoamidopropyl betaine is a foaming agent and is incorporated to eliminate production difficulties. Thanks to its anti-irritant and antiseptic properties, Cocoamidopropylbetaine improves the action of hydrocolloids.

The different hydrocolloid sponge structures produced with cocoamidopropylbetaine were tested antibacterially. It was observed here that the antibacterial effect has intensified.

The combination of the components, the simplification of the production process and the additional antibacterial property represent the innovation of this invention.

Growth factors, antiseptics, and antibacterial materials can be used in wound covering, but for the first time, the ceramide molecule is used in such a wound covering.

By sucking the exudate into the hydrocolloid-based structure, the cell transition of the growth factors in the first layer is induced. Over a period of 48 hours, the first layer melts and the wound surface comes into contact with the second layer. In the second layer, the ceramide molecule, which has the property of regulating the cell proliferation-promoting apoptosis mechanism and making the wound not extremely dry, penetrates into the exudate. The molecules that act at the cellular level help control the bacterial population and heal the wound.

The results in animal application show that the hydrocolloid sponge of the invention shortens the normal healing process by 1/3. Therefore, the hydrocolloid sponge according to the invention is mainly suitable for use in chronic wounds.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• WO 94/17137 [0026]
• US 2012/0059301 A1 [0026]
• US 2011/0257617 A1 [0026]
• WO 2007/048193 [0026]
• WO 2004/080500 A1 [0026]
• US 8147469 B2 [0026]
• US 2011/0071227 A1 [0026]
• US 2003/0108607 [0026]
• US 2002/0106400 A1 [0026]
• WO 2011/008842 [0026]
• US 2009/0297588 A1 [0026]

Claims (9)

A process for producing hydrocolloid sponges characterized by adding active ingredients to a combination of a silk peptide and a hydrocolloid polymeric material. A method according to claim 1, characterized in that the active ingredients include the growth factors EGF (Epidermal Growth Factor, FGF (Fibroblast Growth Factor) and / or IGF (Insulin-like Growth Factor). Method according to at least one of the preceding claims, characterized in that distilled water is added. Method according to at least one of the preceding claims, characterized in that an antiseptic, preferably the antiseptic propylbetaine, is added. Method according to at least one of the preceding claims, characterized in that substances for the protection of cells, preferably ceramides, are added. Method according to at least one of the preceding claims, characterized in that a solvent, preferably a liquid solvent, is added. Method according to at least one of the preceding claims, characterized in that a foam conveyor, preferably the foam conveyor Cocoamidopropylbetain (CAPB), is added. Use of a sponge for wound covering produced by a method according to any preceding claim. Sponge produced by a process according to at least one of claims 1 to 7.

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