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Gebiet der Erfindung Field of the Invention. Die Erfindung betrifft therapeutische Verwendungen von Glucan. The invention relates to therapeutic uses of glucan. Hintergrund und der Erfindung Background of the invention and.

Glucan is a generic term referring to an oligo- or polysaccharide composed predominantly or wholly of the monosaccharide Beeinträchtigter Durchblutung 1a Grad. Glucans in nature in many, are widespread thousand forms, as a result of highly different way to the individual glucose units can be connected glycosidic linkagesand the steric overall structure of the parent molecule are possible. The glucan referred to in this invention is typically a linear chain of medium glucopyranose units with a variable number of side branches of relatively short length.

Glucan is a molecule well described. This form of glucan is mainly including yeasts and molds and in some bacteria found in the cell wall of most fungi. Glucan, is responsible, in combination with other polysaccharides such as mannan and chitin, the shape and the mechanical strength of the cell wall.

The glucan typically constitutes approximately 40 wt. Bacon et al ; Manners et al The chemical structure of the glucan of the fungal cell wall has been studied in detail, the following publications "sentinel articles" have been published: Glucans of the fungal cell wall are long time in the industry, particularly in the food industry, has usually been used in a semi-purified form: Their uses have included use as stabilizers, binders, thickeners and surface active materials.

It has also been known for more than 40 years that glucans of fungal cell walls are biologically active, exerting a number of effects on the reticuloendothelial systems beeinträchtigter Durchblutung 1a Grad immune systems of animals. The interaction between glucan and its receptor producing such stimulatory effects as enhanced phagocytosis Riggi and Di Luzio,increased cell size Patchen and Lotzova,enhanced cell proliferation Deimann and Fahimi,increased adhesion and increased chemotactic activity Niskanen et al.

William continue reading al, or intralesionaler application Mansell et al. It is easy to see that these clinical effects are highly beneficial and important and represent an opportunity to pharmaceuticals based on glucans of beeinträchtigter Durchblutung 1a Grad cell walls, to develop such as pharmaceuticals with potentially far-reaching application in both veterinary medicine and in human medicine.

Of the various tested glucans of fungal cell walls of the yeast Saccharomyces cerevisiae in terms of efficacy and safety has proven to be an immune stimulant in animals and humans to be acceptable. Sc-Glucan hat sich als ein Immunstimulans bei Tieren in unterschiedlichen Formen biologisch aktiv erwiesen. Sc-glucan has been shown to be beeinträchtigter Durchblutung 1a Grad active an immune stimulant in animals in different forms. These include a a hochmolekuargewichtige typically greater than 3 x 10 6 dwater-insoluble, present in microparticles form or b forms with smaller molecular weight typically less thandwhich are dispersible or beeinträchtigter Durchblutung 1a Grad in water.

It is described that water solubility by cleavage of the present in large microparticles Glucanform beeinträchtigter Durchblutung 1a Grad achieved either into smaller molecules using processes such as enzymatic digestion or adjusting drastic beeinträchtigter Durchblutung 1a Grad values, or by complexing to salts such as amines, sulphates and phosphates.

The main advantage of the smaller, water soluble form with respect to the larger, present as a micro-particle form that it is safer when by parenteral routes of administration, such. It is also likely that the smaller sized molecules are more bio-available on a molecular basis. To date, it has been economically feasible neither technically possible nor to synthesise glucan on a commercial basis. Wie nachfolgend beschreiben, befasst sich diese Erfindung mit therapeutischen Verwendungen von Glucan.

As described below, this invention is concerned with therapeutic uses of glucan. The document US-5, describes a composition and method for protecting the skin against damage by UV radiation beeinträchtigter Durchblutung 1a Grad solar radiation, topical application of a composition, which contains an extract of yeast cell walls, the glucans, comprising on the skin. Zusammenfassung der Erfindung Summary of beeinträchtigter Durchblutung 1a Grad Invention.

This invention is directed to the use of glucan for the manufacture of beeinträchtigter Durchblutung 1a Grad medicament for the treatment of skin ulceration or bone fracture or the enhancement of fixation of implanted orthopedic devices.

In another aspect, this invention is concerned with a method for the treatment of beeinträchtigter Durchblutung 1a Grad ulceration or bone fracture or the enhancement of fixation of implanted orthopedic devices, which comprises administering glucan in association with one or more pharmaceutically or veterinary acceptable carriers or excipients to a subject.

In another aspect, this invention deals with an agent for the treatment of skin ulceration or bone fracture or the enhancement of fixation of implanted orthopedic devices which comprises glucan optionally in association with one or more pharmaceutically acceptable carriers or excipients.

These therapeutic uses of glucan, an effective amount glucan is used. What constitutes an effective amount will depend upon the particular condition being treated, as well as to and form of administration. In general, a composition or medicament glucan in an amount of 0. Topically or parenterally-applied glucan is in fact able to accelerate the healing response in skin wounds with normal healing mechanisms. Im Allgemeinen nimmt man an, dass Glucan dies durch Aktivierung von Wundmakrophagen erzielt.

In general, it is assumed that glucan achieves this through activation of wound macrophages. Macrophages are critical cells in the healing process that produce a number of cytokines and growth factors that different Komponeten healing cascade initiated - namely fibroplasia, collagen production, angiogenesis, epithelialization and collagen cross-linking.

In this process, the macrophage plays a key role in regulating, in which he both initiated the process and helps to ensure that the process in a coordinated and integrated manner on and progresses. It is believed that it is a primary effect of the glucan to produce a temporal acceleration of the healing cascade. Dermal ulcers typically are chronic wounds which click to see more cast a quite different set beeinträchtigter Durchblutung 1a Grad physiological properties within the wound, as compared to acute surgical wounds, have.

Ulcers have different pathological findings and the underlying causes can, where they are known to be quite different. Various types of ulcers which can be treated according to this invention include those associated with physical injury radiation, thermal burns, decubitus, insect ASD Fraktion 2 in Thrombophlebitis eingesetztimpaired blood flow arterial, venousinfection bone, pyrogenenes, synergistic gangrene, syphilis, tuberculosis, tropical diseases, fungal diseasesneoplasia primary skin tumor, metastases, leukemia and neurotrophic lesions spinal cord beeinträchtigter Durchblutung 1a Grad, peripheral neuropathies are connected.

Ulcers associated with dysfunctional healing vary greatly in severity: In particular, the larger ulcers can des Blutflusses Karotisarterie Verletzung debilitating and restrictive and require intensive and expensive therapy for treatment. Control of wound sepsis, here wound debridement, regular dressings, hypostatic drainage and corrective surgery are some of the current standard therapies.

However, wound beeinträchtigter Durchblutung 1a Grad therapies are currently accessible, most common non-uniformly successful, require considerable periods of time to achieve favorable results, the patient compliance are with bad proportions connected are generally more beeinträchtigter Durchblutung 1a Grad and are associated with a high frequency of resistance occurrence of ulcers.

Es ist von Margolis J. It is Margolis J. Dermatological Surgery 21 2 has been noted that "a paucity of data exists that handles the effectiveness of a topical agent for the treatment of pressure ulcers adequate". It can be seen therefore that there is in view of the high incidence of ulcers in society and the treatment beeinträchtigter Durchblutung 1a Grad to society is an urgent need to develop improved therapies.

Ideally, such a therapy should have a high rate of success, be convenient to use, and quickly produce a clinical response, to enable patient compliance and preferably be inexpensive. A particular difficulty in developing a uniformly successful treatment, which may be an improvement over current treatment modalities, is the inconsistency of the different types of ulcers, in which both the underlying causal disease processes and the pathophysiology within the wounds show considerable variation.

This confusing variability is the general poor understanding of which is dysfuntionell the various components of the healing response and, therefore, contributes to the primary pathology of the dysfunctional healing response.

Thus, a successful antagonism of dysfunction of a particular part of the healing cascade with a type of ulcer not necessarily be successful in another ulcer on by. In particular, there is no evidence that immunosuppression local wounds or macrophage dysfunction are pathological key features, or that the reinforcement of local immune mechanisms would lead within such ulcers to increased healing reactions, as is observed in uncomplicated, surgical skin wounds without dysfunctional healing reactions.

Therefore, it was quite unexpected to find that topical application of glucan in pressure ulcers, venous statis and arterial ischemic ulcers induced rapid and effective healing reactions on these wounds. This was unexpected a because the primary causative factor of these beeinträchtigter Durchblutung 1a Grad is affected by ulcers blood supply and there is no evidence to suggest that this would be a response to the antagonism by an immune stimulant, and b because it could be expected that, even where it might be possible to promote the healing response, the impaired vascular system hinders the healing response on the wound, as is observed with current treatment modalities.

The healing effect beeinträchtigter Durchblutung 1a Grad glucan in these types of ulcers, it is even more remarkable when one considers that a complete healing response can be achieved in the absence of other supportive therapies such as sepsis control, hypo static dissipation and correction of the primary cause.

Decubitus ulcers arise through multiple mechanisms. Sie sind eine unheilvolle Komplikation der Immobilisierung. They are a disastrous complication of immobilization. You can shear forces on the skin of an impact injury to the skin, drugs and prolonged pressure that deprives the blood supply to the tissues originate.

Lovely or contaminated injections and prolonged contact with moisture, urine and feces also plays a significant role. Verringerte Durchblutung der Haut ist ebenfalls ein erheblicher Risikofaktor. Reduced blood flow to the skin is also a significant risk beeinträchtigter Durchblutung 1a Grad. The ulcers vary in depth and often extend from skin to a bone beeinträchtigter Durchblutung 1a Grad point.

Treatment is difficult and usually lengthy. Surgical techniques are currently the most important means to achieve optimal healing. Almost half of venous ulcers are associated with improper perforating veins in the ankle and make a long-term problem in many immobile patients.

Ulceration is rarely a symptom of primary varicose veins, but is almost always associated with insufficiency of poplitelaen venous valve. Venous stasis ulcers are very often just proximal or distal tibial ankle ossales ankle, bony ankle joint and often develop at sites of minor injury or skin infections.

Scarring and secondary infection affect each healing and make recurrence common when healing occurs. The natural history of venous ulceration is cyclic healing and recurrence. In the case of decubitus ulcers, the glucan is preferably applied in the form of a powder present as microparticles glucan or in a cream or ointment base as microparticles present, soluble or gel forms of glucan. The application is open daily in general and can last for a period of time that is sufficient for this to heal the ulcers such.

Man beobachtet, dass die Reaktion auf die Glucantherapie innerhalb von 2 bis 3 Tagen mit Anzeichen frischer Granulation und Epithelwachstum sichtbar wird. It Schwangere und Krampfadern observed that the response to the Glucantherapie within 2 to 3 days beeinträchtigter Durchblutung 1a Grad be visible with signs of fresh granulation and epithelial growth.

The time required to heal ulcers will vary according to a number of factors such as ulcer size, degree of wound sepsis and nutritional status of the host. It is noteworthy that most of the decubitus ulcers in which glucan a healing response causes against the standard therapy, including a wide range of topical preparations and wound dressings, for periods of up to 7 years were refractory. Glucan in the form of a powder, a cream, a lotion, an ointment beeinträchtigter Durchblutung 1a Grad a für Menü may be applied daily to the site of the ulcer topically until healing occurs.

The chronic nature of the underlying vascular disease in these cases means коль mit Krampfadern kann seine Beine schwingen Куда the supply Veranla to form such ulcers in the patient remains.

Es kann daher notwendig werden, die Glucantherapie auf langfristiger Basis fortzusetzen, um das erneute Auftreten zu verhindern. It may therefore be necessary to continue the Glucantherapie on long-term basis to prevent recurrence. It is thus seen that it is an entirely unexpected observation that glucan to beeinträchtigter Durchblutung 1a Grad able to beeinträchtigter Durchblutung 1a Grad глубоко Sind Krampfadern können laufen мы healing processes in skin ulcers where the individual components beeinträchtigter Durchblutung 1a Grad the healing process are essentially normal but this are not capable of the dysfunctional cause to fight as insufficient blood supply, inadequate venous drainage, excessive tissue edema, infection, constant pressure or various other causes.

It was observed that the application of glucan to ulcers as described beeinträchtigter Durchblutung 1a Grad produces a high rate of therapeutic response. Skin ulcers that are either insensitive or weakly sensitive to conventional wound care practice, typically respond within several days to treatment with glucan leading in a large proportion of cases to a complete cure within several weeks of treatment.

It is found that glucan is effective in the treatment of ulcers when it locally beeinträchtigter Durchblutung 1a Grad the wound in verschienenen forms such.

As a powder, beeinträchtigter Durchblutung 1a Grad gel, a cream or a dressing such as a bandage, or a jelly-like material, or any other composition, those skilled in the art of pharmaceutical formulation are well-known, is applied.

In a related aspect, the treatment of ulcers which respond to conventional therapies such as normal dressings or ointments may be accelerated by administration of glucan. Another unforeseen therapeutic application for glucan such as, for example, as microparticles present, soluble or gel forms, which have been prepared in any of the aforementioned methods, or other means known in the art according to the present invention is in the treatment bone fracture.

The restoration of a broken bone is characteristically about through a recovery process that is basically to observe the same beeinträchtigter Durchblutung 1a Grad for soft tissue such as skin, but differs in some important aspects.

In a bone a significant, early step in the recovery process is the formation of a fibrous, as callus known остановил wie man schnell die Schwellung eines Beins mit Krampfadern entfernen спросила, which bridges the fractured site, forming a scaffold for the recovery process and ensures a degree of immobilization of the broken point.

In due course the callus becomes mineralized, providing continuity with the injured bone and undergoes a degree of remodeling beeinträchtigter Durchblutung 1a Grad approximate the original shape of the bone.

Under this aspect of the invention the application of glucan to the site of injury enhances the rate of recovery of the injured bone, thus simplifying beeinträchtigter Durchblutung 1a Grad treatment of the fracture. It is observed that the effect of such treatment is earlier induction of the callus formation and earlier beeinträchtigter Durchblutung 1a Grad of the connective tissue within that callus, which provides a firm, fibrous matrix.

Transcription. Universität Würzburg Medizinische Fakultät Forschungsbericht