Pharmaceutical composition for healing a wound

Abstract

The invention relates to a pharmaceutical composition comprising an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, having an amino acid sequence, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO:1 or SEQ ID NO:2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO:1 or SEQ ID NO:2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment codes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO:1 or SEQ ID NO:2 and at least one further constituent for use in supporting and / or promoting the healing of a wound on a human or animal organism.

Description

[0001] Pharmaceutical composition for healing a wound

[0002] The invention relates to a pharmaceutical composition comprising an isolated sCD83 polypeptide for use in supporting and / or promoting the healing of a wound of a human or animal organism, as well as for use as a medicament for supporting and / or promoting the healing of a wound, as a medicament for treating the same and for use in a therapeutic method or in a non-therapeutic method for supporting and / or promoting the healing of a wound and treating the same.

[0003] Every human or animal organism has a specific pathway for wound healing, which is usually initiated by the release of blood and its messenger substances. There are three phases of wound healing, beginning with the cleansing phase, which expels damaged cells and flushes out foreign substances and / or pathogens. This is followed by the granulation phase, in which new tissue is built up to close the wound gap. In the third phase, the epithelialization phase, the organism covers the healing wound with skin.

[0004] Despite this automated healing cascade of the body, it is necessary under certain circumstances to support and / or promote wound healing, particularly when there is a disturbance in at least one of the three wound healing phases and / or the healing cascade has not been initiated. There is therefore a great and ever-growing need to support and / or promote the healing of a human or animal wound in a reliable, simple, effective, tolerable, dermatologically and / or health-safe, low-side-effect, well-tolerated, cost-effective, targeted, and specific manner. At the same time, it is necessary that the wound heals over the long term.The invention therefore has for its object to provide a pharmaceutical composition for supporting and / or promoting the healing of a wound of a human or animal organism in order to avoid the above-mentioned disadvantages of the prior art, while at the same time being characterized by high efficacy, specificity, tolerability and / or reliability, as well as simple, low-error, time- and cost-efficient application.

[0005] This object is achieved in a surprisingly simple but effective manner by a pharmaceutical composition for supporting and / or promoting the healing of a wound of a human or animal organism according to the teaching of the independent claims.

[0006] According to the invention, a pharmaceutical composition comprises an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, having an amino acid sequence, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 and at least one further component for use in supporting and / or promoting the healing of a wound of a human or animal organism.

[0007] The invention is based on the fundamental idea that the sCD83 polypeptide is particularly well-suited as an active ingredient in a pharmaceutical composition due to its primary effect on regulatory effects in the context of inflammatory processes and / or (wound) healing processes. It has been recognized that the sCD83 polypeptide, as the active ingredient in the pharmaceutical composition, is an important checkpoint for the termination of inflammation and the initiation of regeneration processes in vivo, in vitro, and / or ex vivo. Therefore, particularly due to its anti-inflammatory and healing-promoting effects, it is particularly well-suited for supporting and / or promoting the healing of a wound in a human or animal organism, as well as for treating the same or as a medicament.It has been recognized that the pharmaceutical composition is suitable for supporting and / or promoting the healing of a wound, wherein the healing can be achieved in particular by the restoration, reconstruction and / or regeneration of bone and / or jaw using bone substitute material or bone graft.

[0008] Within the scope of the invention, it has been recognized that the pharmaceutical composition comprises at least one sCD83 polypeptide, preferably 2, 5, 10, 50, 100, 1,000, 10,000 or more sCD83 polypeptides, with an amino acid sequence, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1, which shows the amino acid sequence of a full-length human CD83 protein (hCD83; as can be seen in GenBank under Q01 151 and Fig. 1), or SEQ ID NO: 2, which shows the amino acid sequence of an extracellular domain of human CD83 (hCD83ext; as can be seen in Fig. 2); and b) an amino acid sequence which comprises at least 70%, preferably at least 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0009] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,

[0010] 96%, 97%, 98%, 99%, 99.10%, 99.15%, 99.20%,

[0011] 99.25%, 99.30%, 99.35%, 99.40%, 99.45%, 99.50%,

[0012] 99.55%, 99.60%, 99.65%, 99.70%, 99.75%, 99.80%,

[0013] 99.85%, 99.90%, 99.95%, 99.96%, 99.97%, 99.98%,

[0014] 99.99%, 99.995%, 99.999%, 99.9995% or 99.995% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70%, preferably at least 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%

[0015] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,

[0016] 94%, 95%, 96%, 97%, 98%, 99%, 99.10%, 99.15%,

[0017] 99.20%, 99.25%, 99.30%, 99.35%, 99.40%, 99.45%,

[0018] 99.50%, 99.55%, 99.60%, 99.65%, 99.70%, 99.75%,

[0019] 99,80 %, 99,85 %, 99,90 %, 99,95 %, 99,96 %, 99,97 %,

[0020] 99.98%, 99.99%, 99.995%, 99.999%, 99.9995% or 99.995% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2. sCD83 polypeptides, nucleic acid and / or amino acid sequences and structures are known to a person skilled in the art. SEQ ID NO: 1 shows the amino acid sequence of a full-length human CD83 protein (hCD83; as found in GenBank under Q01151 and Fig. 1). The corresponding nucleic acid sequence of the human CD83 polypeptide of SEQ ID NO: 1 can be found in GenBank under No. ZI 1697, shown in patent specification US 7,169,898 and shown in the publication of the international patent application WO 2009 / 142759 A1. The sequence in SEQ ID NO:1 has 205 amino acids. Amino acid residues 1-19 of SEQ ID NO:1 correspond to a signal sequence that is cleaved from the mature protein (amino acid residues 20-205).Other human CD83 sequences can be found in GenBank under NP 001035370 [CD83 antigen isoform b, Homo sapiens], NP_004224 [CD83 antigen isoform a, Homo sapiens], EAW55353 [CD83 antigen isoform CRA c, Homo sapiens], EAW55352 [CD83 antigen isoform CRA b, Homo sapiens], and EAW55351 [CD83 antigen isoform CRA a, Homo sapiens]. Such sequences can be used to determine conserved domains.

[0021] SEQ ID NO:2 shows the amino acid sequence of a human CD83 extracellular domain (hCD83ext; as shown in Fig. 2), as shown in amino acid residues 20-144 of SEQ ID NO:1 and in the published international patent application WO 2009 / 142759 A1. The sequence in SEQ ID NO:2 has 125 amino acids. The transmembrane domain and the cytoplasmic domain correspond to amino acid residues 145-166 of SEQ ID NO:1 and amino acid residues 167-205 of SEQ ID NO:1, respectively. Wild-type hCD83ext contains three glycosylation sites (i.e., amino acid residues 60, 77, and 98 of SEQ ID NO:2) and five cysteine ​​residues (i.e., amino acid residues 27, 35, 100, 107, and 129 of SEQ ID NO:1, corresponding to amino acid residues 8, 16, 81, 88, and 110 of SEQ ID NO:2).

[0022] The term "pharmaceutical composition" is known to one of skill in the art and refers to a mixture of the sCD83 polypeptide, as defined in detail elsewhere, as the active ingredient and at least one other ingredient. Such other ingredients are known to one of skill in the art and defined in detail elsewhere. Furthermore, the pharmaceutical composition may also contain other carriers, excipients, or non-toxic, non-therapeutic, non-immunogenic stabilizers, and the like.

[0023] The term "CD83 polypeptide" is known to those skilled in the art and refers to a molecule from the immunoglobulin superfamily, which is a differential marker for mature dendritic cells. The soluble form of the CD83 polypeptide, sCD83 polypeptide, binds to both immature and mature dendritic cells and plays a crucial role in wound healing, particularly in specific mediators of wound healing, such as cytokines and growth factors, and in tool-like receptor (TLR)-mediated signaling events. Within the scope of the invention, it has been recognized that the sCD83 polypeptide can alter the transcriptome during early wound healing and thus promote the wound regeneration process. Preferably, the sCD83 polypeptide is an isolated sCD83 polypeptide.The term “isolated sCD83 polypeptide” is known to a person skilled in the art and means that the sCD83 polypeptide, the at least 70% identical amino acid sequence and / or the amino acid sequence encoding a fragment of a polypeptide which is at least 70% identical, is separated from cellular and / or other components.

[0024] A person skilled in the art will further understand that the terms “polypeptide,” “peptide,” “amino acids,” “glycoprotein,” and “protein” are used interchangeably to describe a polymer of amino acid residues. Naturally occurring amino acids are those encoded by the genetic code as well as those amino acids that can be modified later. Polypeptides can exist as reserve substances, as transport and / or signaling molecules, as structural molecules, as protective and / or defense molecules, and / or as metabolically active molecules, and they can perform various functions inside and / or outside a cell or in the organism. For example, polypeptides can have anti-inflammatory, antiviral, and / or antibacterial effects and thus, due to their properties or functions, support and / or promote wound healing.Polypeptides can exist as single-stranded, double-stranded, or triple-helical molecules, or as folded structural proteins. Examples of proteins include molecules that act as growth-promoting substances, enzymes, or molecules that promote cell division.

[0025] According to the invention, the pharmaceutical composition is suitable and / or intended for use in supporting and / or promoting the healing of a wound of a human or animal organism. In this regard, it is necessary that the pharmaceutical composition be brought into contact with the wound using methods and measures known to a person skilled in the art, for example, as described elsewhere.

[0026] The term "supporting wound healing" is known to those skilled in the art and, in the context of the invention, refers to improving, accelerating, strengthening, enhancing, promoting, and / or initiating the healing process. The term "promoting wound healing" is known to those skilled in the art and, in the context of the invention, refers to benefiting, being helpful, benefiting, contributing to, accelerating, and / or stimulating the healing process. Those skilled in the art are aware that these terms can overlap, complement, and / or reinforce each other.

[0027] The term "wound healing" is known to a person skilled in the art and, as described in detail elsewhere, relates to the closure of a wound in a human or animal organism, i.e., a defect in the protective covering tissue on external and / or internal body surfaces, such as skin, teeth, tissues, organs, and / or mucous membranes, with or without tissue loss, as well as through the restoration, reconstruction, and / or regeneration of the damaged tissue, such as soft tissue, the external and / or internal body surfaces, bones, the jaw, and / or the damaged cells. It is also conceivable that wound healing includes wound aftercare and wound care.

[0028] It is assumed that the definition and / or the explanations of the above terms apply to all aspects described in this description below, unless otherwise stated.

[0029] According to the invention, a pharmaceutical composition comprising an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, with an amino acid sequence is further proposed, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 and at least one further component for use as a medicament in supporting and / or promoting the healing of a wound of a human or animal organism and / or as a medicament for treating the wound.

[0030] The term "medicinal product", or medical device, is known to a person skilled in the art and relates to the suitability of the pharmaceutical composition to support and / or promote wound healing and / or to treat it, as described elsewhere. It is understood by a person skilled in the art that the definition as a medicinal product is based on the relevant legal regulations of the national pharmaceutical laws and / or the legal regulations of the national medical devices. Thus, the term refers to a pharmaceutical composition in a therapeutically effective dose, as mentioned in detail elsewhere. The medicinal product can be formulated for various routes of administration, which are described in detail elsewhere. A therapeutically effective dose refers to the amounts required to support and / or promote wound healing and / or to partially or completely treat the wound, i.e.up to the completion of wound healing. Therapeutic efficacy and toxicity can be determined using standard pharmaceutical methods in cell cultures or experimental animals, e.g., ED50 (the dose that is therapeutically effective at 50%) and LD50 (the dose that is lethal at 50%). The dose relationship between therapeutic and toxic effects is the therapeutic index, which can be expressed as the LD50 / ED50 ratio. The dosage regimen is determined by the attending physician and other clinical factors. As is well known in medicine, the appropriate dosage depends on many factors known to those skilled in the art, including size, body surface area, age, the substance to be administered, gender, time and route of administration, general health, and other concomitantly administered medications. Progress can be monitored by periodic assessment.

[0031] The term "treatment" refers to any improvement, partial or complete, in a wound on a human or animal organism compared to an untreated organism, with this improvement being based primarily on progress in wound healing. It is understandable that progress in wound healing also occurs with partial, partial or complete healing of the wound. It is therefore also conceivable that complete healing is possible. It is understood that a treatment may not be successful in all wounds on human or animal organisms to be treated. However, the term presupposes that the treatment is successful for a statistically significant proportion of the organisms (e.g. a cohort in a cohort study).Whether a part is statistically significant can be readily determined by a person skilled in the art using various known statistical evaluation tools, e.g., determining confidence intervals, p-value determination, Student's t-test, Mann-Whitney test, etc. Preferred confidence intervals are at least 90%, 95%, 97%, 98%, or 99%. The p-values ​​are preferably 0.05, 0.01, 0.005, or 0.0001.

[0032] Furthermore, according to the invention, a pharmaceutical composition comprising an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, with an amino acid sequence is proposed, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2;and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 and at least one further component for use in a therapeutic method or in a non-therapeutic method in assisting and / or promoting the healing of a wound of a human or animal organism and / or in a therapeutic method or in a non-therapeutic method for treating the wound.;

[0033] By means of the pharmaceutical compositions according to the invention, it is possible, regardless of the method of administration, to induce, accelerate, and / or treat high-quality wound healing, so that an inflammatory reaction of the wound, along with swelling, pain, and / or tissue damage, is effectively reduced. The present invention thus demonstrates for the first time that the pharmaceutical composition containing the sCD83 polypeptide has proregenerative potential for the treatment of wounds while simultaneously exhibiting no or only mild side effects.

[0034] Advantageous further developments of the invention, which can be implemented individually or in combination, are presented in the subclaims.

[0035] In a further development of the invention, it is conceivable that the at least one further component is a stabilizing agent, a wetting agent, a pharmaceutical carrier, a pharmaceutically acceptable carrier, an active carrier, an inert carrier, a diluent, a pharmaceutically acceptable diluent, a further and / or additional pharmaceutical active ingredient, a separating agent, a mixture, and / or a combination thereof. Preferred diluents include water, alcohols, physiological saline solutions, buffers such as phosphate-buffered saline solutions, syrup, oil, water, emulsions, various types of wetting agents, and the like. The carrier must be acceptable in the sense that it is compatible with the other components of the composition and that it is not harmful, in particular harmless, to the organism. The pharmaceutical carrier used can be a solid, a gel, or a liquid.Examples of solid carriers are lactose, terra alba, sucrose, talc, gelatin, collagen, cellulose, agar, pectin, acacia, magnesium stearate, stearic acid, a collagen membrane, a bone substitute material, and the like. Similarly, the carrier or diluent may contain a time-delay material well known in the art, such as glycerol monostearate or glycerol distearate alone or with a wax. These suitable carriers include those listed above and other carriers known in the art, such as Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania, the European Pharmacopoeia, the Homeopathic Pharmacopoeia of the United States, or HAB. The pharmaceutically acceptable diluent is selected so as not to impair the biological activity of the combination. Examples of such diluents are distilled water, physiological saline, Ringer's solutions, dextrose solution, and Hank's solution.

[0036] In a further development, it is conceivable that the pharmaceutical composition is a solid, such as chewing gum, candy, a tablet, as a particle, a chip, a ring, a block, a shell, a granulate, a membrane or a powder, a paste, such as toothpaste or a cream, a gel, such as dental gel, a foam, an ointment, a liquid, such as a rinse, a mouthwash, a bath, a solution or a drinking ampoule, an injection, such as an active or passive vaccine, a mixture and / or a combination thereof. The term “membrane” is known to a person skilled in the art and refers to a thin separating layer that surrounds a cell compartment and / or separates it from other tissue, e.g. on external and / or internal body surfaces.It is conceivable that the membrane separates tissue types and thus, for example, prevents and / or delays the ingrowth of connective tissue into the wound and / or the defect. The membrane can be resorbable, e.g. made of collagen or polyactide, or non-resorbable, e.g. made of polytetrafluoroethylene or a metal such as titanium. Furthermore, the membrane can be of native, biological or synthetic origin and / or additionally treated, such as a membrane obtained from the patient’s own blood (PRGF membrane; plasma rich in growth factors). Within the scope of the invention, it is conceivable that the solid can be treated, coated, wettable, impregnated and / or saturated with the liquid, for example the sCD83-containing solution. This offers the advantage that the pharmaceutical composition can be applied to, on and / or in the area of ​​the wound to be healed.In this way, it is ensured that the sCD83 polypeptide comprised in the pharmaceutical composition, as well as other components comprised in the composition, as described in detail elsewhere, come into contact with the wound to be healed in order to support, promote, and / or treat the healing process. The exact, individually recommended dosage, as described elsewhere, may in principle depend on other parameters that are well known to the person skilled in the art. For example, children may receive a different dosage than adults. Whether the dosage needs to be adjusted can be readily determined by the person skilled in the art using various known calculation tools.

[0037] Furthermore, it is conceivable that the pharmaceutical composition can be administered systemically, topically, dermally, intramuscularly, subcutaneously, orally, rectally, retrogradely, and / or intravenously. This also ensures that the sCD83 polypeptide comprised in the pharmaceutical composition, as well as other components comprised in the composition, as described in detail elsewhere, come into contact with the wound to be healed in order to support and promote the healing process and / or treat the wound. It is conceivable that the pharmaceutical composition is applied, dripped on, injected, introduced, swallowed, and / or reaches the wound to be healed by flow. The exact, individually recommended dosage, along with other parameters, is described elsewhere.

[0038] Furthermore, it is conceivable that the healing of a wound relates to the closure of a defect in a protective covering tissue on an external and / or internal body surface and / or the restoration, reconstruction and / or regeneration of a damaged tissue, in particular a soft tissue, the external and / or internal body surface, bones, a jaw and / or a damaged cell, as described in detail elsewhere.

[0039] It is further conceivable that an aid supports and / or promotes the healing of a wound, in particular the restoration, construction and / or new formation of bone and / or jaw, wherein the aid is selected from a bone material, in particular an autologous, allogeneic, xenogeneic and / or synthetic bone material, a bone replacement material, a bone transplant or a carrier material. The term “autologous bone material” refers to a bone taken from another location of the same individual. The term “allogeneic bone material” refers to human or animal donor bone from another individual. The term “xenogeneic bone material” refers to bone material from another species. The term “synthetic bone material” refers to a resorbable or non-resorbable material which serves to form bone.Conceivable materials with their inherent properties are known to a person skilled in the art, such as ceramic or beta-tricalcium phosphate. Furthermore, it is conceivable that these materials could be produced partially or entirely from ceramic, algae, or coral. The term "bone replacement material" refers to an artificially produced, bioactive, biologically inorganic compound derived from animal, plant, and / or human tissue, such as algae or coral, which may or may not be resorbable. In the context of the present invention, the term "bioactive" means that bony integration and, associated with it, a strong bond between the vital bone and the bone replacement material is achieved.The term "bone transplant" refers to an organic, biological, native, or synthetic bone transplanted for therapeutic purposes, or a bone substitute material, as described elsewhere, or a carrier material obtained from blood and / or plasma concentrate and / or centrifuge, such as a centrifuge from autologous blood, such as platelet-rich plasma (PRP) or autologous conditioned plasma (ACP). The bone transplant and / or the carrier material can, as described elsewhere, be in the form of a solid, for example in the form of chewing gum, as particles, as a chip, as a ring, as a block, as a shell, as granules, as a powder or as a membrane, as a paste, as a gel, as a foam, as an ointment, as a liquid, in particular as a rinse, as a mouthwash, or as a solution, as described elsewhere.

[0040] In addition, it is conceivable that the wound is a mechanical wound, such as a cut, puncture, slash, bite, abrasion, laceration, crush, gunshot, exfoliation and / or laceration, a decubitus ulcer, a mixture and / or combination thereof, a thermal wound, such as a burn wound caused by burning, scalding and / or frostbite, a chemical wound, such as a chemical burn of the skin and / or mucous membranes caused by acids or alkalis, a radiation-induced wound, such as by irradiation of the skin with ionizing radiation such as X-rays, by radioactive isotopes and / or by UV radiation, a surgical wound, such as a pre- and / or post-operative wound and / or a wound induced by an operative procedure such as surgical and / or dental intervention, an infected wound, for example by a viral and / or bacterial infection such as periodontitis, a disease-induced wound,such as an ulcer and / or cancer, and / or a canker sore.

[0041] Furthermore, it is conceivable that the wound is a wound of the respiratory tract, the teeth, in particular in the case of tooth extraction, root resection and / or cystectomy, the mouth, the gums, in particular the periodontal pocket, the oral cavity, the lips, the tonsils, the tongue, the jaw, the bones, the eye, the musculoskeletal system, the blood, the gastrointestinal tract, such as the large intestine, the small intestine, the duodenum, the stomach, the liver, the gallbladder and / or the pancreas, the skin, the mucous membrane, the cardiovascular system, the mind, the immune system, the nervous system, the metabolism and / or the urogenital tract.

[0042] The present invention further relates to an oral delivery system containing a pharmaceutical composition according to the invention comprising an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, having an amino acid sequence, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 and at least one further component.

[0043] Preferably, the oral delivery system is in the form of a chewing gum, a paste, a gel, a foam, an ointment or a liquid, in particular a rinse, a mouthwash or a solution.

[0044] The oral delivery system according to the invention serves, in particular, to promote wound healing and inhibit inflammation in the mouth and throat, such as in the sulci. Chewing gum has the advantage, among other things, of counteracting a delayed onset of action, since it can be used by the patient over an extended period without any problems.

[0045] Chewing gum is generally composed of the following raw material groups: gum base, plasticizers, fillers, lubricants, fats, emulsifiers, flavors, colors, antioxidants and edible acids for flavoring.

[0046] Either natural substances such as chicle, gutta-percha, latex, benzoin resins or gum arabic, or consistency-giving, synthetic thermoplastics such as polyvinyl acetate in quantities of up to 65% of the chewing mass, poly-butadiene-styrene, polyisobutylene, isoprene, polyvinyl ether and polyethylene can be used as chewing mass.

[0047] Typical plasticizers are emulsifiers, resins, waxes, or glucitol. Typical fillers are magnesium stearate, chalk, calcium carbonate, silicate, or cellulose. The fillers or technical additives maintain the flowability and prevent the particles from sticking together under low pressure. Mineral oils, microcrystalline waxes, or vegetable oils are typically used as lubricants, greases, or emulsifiers. These additives prevent sticking of the tools or on the tools.

[0048] Conventional chewing gum can be a major cavities-promoting factor due to its high sugar content, but it also massages the gums and stimulates saliva production. The added flavorings also make chewing gum refreshing, invigorating, and / or thirst-quenching.

[0049] To prevent the aforementioned caries-promoting effect of sugar in chewing gum, sugar-free chewing gums have long been marketed. In these, the sugar is replaced with sugar substitutes. These are primarily sorbitol and xylitol. The chewing gums according to the invention serve to support dental and oral hygiene and to treat / prevent pathogen-induced pathological changes. The chewing gums according to the invention are usually sugar-free and, similar to toothpaste, contain traces of minerals for tooth regeneration. The chewing gum according to the invention can also comprise at least one abrasive or at least one abrasive substance, in particular calcium carbonate, calcium phosphates, metaphosphates, silicic acid, aluminum oxides, silicates, and / or talc.

[0050] Furthermore, the chewing gum according to the invention can contain at least one suspending agent or a humectant, in particular water, glycerin, propylene glycol and / or sorbitol syrup, as well as at least one thickening, stabilizing and / or binding agent, in particular gels, starches, alginates, oils and / or cellulose gum.

[0051] To improve the taste properties, at least one aromatic substance, at least one sweetener and / or at least one sugar substitute, in particular menthol, peppermint oil, sodium saccharin, aspartame, acesulfame, sorbitol, malitol, xylitol and / or fructose, may be added to the chewing gum.

[0052] In addition, the chewing gum according to the invention may contain further chemical additives, dyes and / or pH regulators, in particular fluorides, astringents, anti-inflammatories, desensitizers, vitamins, panthenol, white pigments and / or sodium hydroxide.

[0053] The oral delivery system according to the invention in the form of chewing gum allows the sCD83 polypeptide to reach the sites of action, particularly the periodontal pockets, particularly effectively. The chewing action presses the chewing gum into the periodontal pocket, where the polypeptide can then exert its effect. In another embodiment of the system according to the invention, it is available as a gel or ointment. In this form, it is usually applied to the periodontal pockets, where it releases the sCD83 polypeptide into the environment.

[0054] Further details, features, and advantages of the invention will become apparent from the following description of the preferred embodiments in conjunction with the subclaims. The respective features can be implemented individually or in combination with one another. The invention is not limited to the embodiments.

[0055] In detail:

[0056] Fig. 1 shows the amino acid sequence of a full-length human CD83 protein (hCD83) as shown in SEQ ID NO: 1; and

[0057] Fig. 2 the amino acid sequence of a human CD83 extracellular domain (hCD83 ext) as shown in SEQ ID NO:2.

[0058] Figure 1 shows the amino acid sequence of a full-length human CD83 protein (hCD83; as found in GenBank under Q01 151 and in SEQ ID NO: 1). Figure 2 shows the amino acid sequence of a human extracellular CD83 domain (hCD83 ext; as found in SEQ ID NO: 2).

[0059] The following embodiments serve merely to illustrate the invention. They are not intended to limit the scope of the claims in any way.

[0060] Examples:

[0061] Example 1 : Widening of lost jawbone for

[0062] Incorporation of an implant. An example of the use of the pharmaceutical composition according to the invention in supporting and / or promoting wound healing is the widening of lost jawbone to accommodate an implant. In this case, prior to transplantation, autologous or allogeneic bone from a human or animal patient is saturated at the defect site with the liquid pharmaceutical composition containing the sCD83 polypeptide. This transplant is then covered and fixed in place with a (collagen) membrane, which is also saturated with the liquid pharmaceutical composition prior to fixation.

[0063] Example 2: Reconstruction of lost jawbone to accommodate an implant

[0064] An example of the use of the pharmaceutical composition according to the invention in supporting and / or promoting wound healing is the augmentation of lost jawbone to accommodate an implant. Bone harvested from another location, or, for example, an allogeneic bone graft, is saturated with the liquid pharmaceutical composition containing the sCD83 polypeptide before transplantation to the defect region. This graft is then adapted and fixed with a membrane that has been similarly conditioned prior to insertion.

Claims

Patent claims 1. Pharmaceutical composition comprising an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, having an amino acid sequence, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 and at least one further component for use in supporting and / or promoting the healing of a wound of a human or animal organism.

2. A pharmaceutical composition comprising an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, having an amino acid sequence, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 and at least one further component for use as a medicament in supporting and / or promoting the healing of a wound of a human or animal organism and / or as a medicament for treating the wound.

3. Pharmaceutical composition comprising an sCD83 polypeptide, in particular an isolated sCD83 polypeptide, with an amino acid sequence, wherein the amino acid sequence is selected from the group comprising: a) an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and b) an amino acid sequence which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2; and c) an amino acid sequence for a fragment of a polypeptide, wherein the fragment encodes a polypeptide which is at least 70% identical to the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 and at least one further component for use in a therapeutic method or in a non-therapeutic method in supporting and / or promoting the healing of a wound of a human or animal organism and / or in a therapeutic method or in a non-therapeutic method for treating the wound.

4. Pharmaceutical composition according to any one of the preceding claims, wherein the at least one further component is a stabilizing agent, a wetting agent, a pharmaceutical carrier, a pharmaceutically acceptable carrier, an active carrier, an inert carrier, a diluent, a pharmaceutically acceptable diluent, a further pharmaceutically active ingredient, a separating agent, a mixture and / or a combination thereof.

5. Pharmaceutical composition according to one of the preceding claims, wherein the pharmaceutical composition is a solid, in particular a chewing gum or a membrane, a paste, a gel, a foam, an ointment, a liquid, in particular a rinse, a mouthwash or a solution, an injection, a mixture and / or a combination thereof.

6. Pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition is administrable systemically, topically, dermally, intramuscularly, subcutaneously, orally, rectally, retrogradely and / or intravenously.

7. Pharmaceutical composition according to one of the preceding claims, wherein the healing of a wound relates to the closure of a defect in a protective covering tissue on an external and / or internal body surface and / or the restoration, reconstruction and / or regeneration of a damaged tissue, in particular a soft tissue, the external and / or internal body surface, bone, a jaw and / or a damaged cell.

8. Pharmaceutical composition according to one of the preceding claims, wherein an aid supports and / or promotes the healing of a wound, wherein the aid is selected from a bone material, in particular an autologous, allogeneic, xenogeneic and / or synthetic bone material, a bone substitute material, a bone transplant or a carrier material.

9. Pharmaceutical composition according to any one of the preceding claims, wherein the wound is a mechanical wound, a thermal wound, a chemical wound, a radiation-induced wound, a surgical wound, an infected wound, a disease-induced wound and / or an aphthous ulcer.

10. Pharmaceutical composition according to the preceding claim, wherein the wound is a wound of the respiratory tract, teeth, mouth, gums, oral cavity, lips, tonsils, tongue, jaw, bones, eye, musculoskeletal system, blood, gastrointestinal tract, skin, mucous membrane, cardiovascular system, mind, immune system, nervous system, metabolism and / or urogenital tract. 1 1. An oral delivery system comprising a pharmaceutical composition according to any one of claims 1 to 10.

12. Oral delivery system according to claim 1 1, characterized in that it is in the form of a chewing gum, a paste, a gel, a foam, an ointment, or a liquid, in particular a rinse, a mouthwash or a solution.

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