Universal method and device for in vivo simulation and in vitro analysis of biochemical body reactions in tissue layers

Background of the Invention

0001Ethical and moral principles forbid normally biochemical tests directly carry out in humans. Therefore, when this becomes necessary, for example, , Samples taken in case of illness or for testing eg blood, tissue, cells etc. or there are substances such as drugs, antibiotics, etc. with the help of introduced or applied applicators.

0002It would make sense to at least measure a part of the reactions of the body directly can. This would allow a large part of the sampling or applications to dispense, which for the most with great effort and pain is connected to the patient, such as in the living tissue sampling in the Nasal mucosa or in the intestinal mucosa.

State of the art

0003Various methods and devices are known, such as, for example, sampler US 4,800,896 from 31.01.1989 or applicators such as US 4,887,611 from 19.12.1989 with which it either samples is possible to remove or substances to apply. Further, in the scientific literature different sampler or applicators describe such as at F. Marcucci and L. Sensi in Clinical & Experimental Allergy, 1989 Vol.19, page 157-162, entitled "A new method for IgE detection in nasal mucosa ".

ADVANTAGES OF THE INVENTION

0004The invention completely replaces sampler and applicators. In the inventive Apparatus and method is part of a complex biochemical Reaction of the body in such a way that simulates a response of the body to an outer Reitz can be in vivo externally so determined or measured in vitro. That's why can with the apparatus and method of the invention, the plurality of existing analytical possibilities as Hochdruckflüssigkeitschromatograpfie (HPLC), gas chromatography (GC), but also enzyme immunoassay (ELISA, RIA, EIA, RAST, EAST, etc.) used to measure the antibody response without major changes will.

0005The simulator is to the nasal mucosa as fixing and site of action in the body the patient's fixed and can, in comparison to existing samplers or Applicators, on very mild and pleasant, the first steps of a complex Action and reaction emulated. The simulator according to the invention can on living organism, a plurality of tests are carried out without damaging or impairing the patient's organism.

The aim of the invention

0006The aim of the presented in this patent invention is that existing Disadvantages of currently prevailing methods and devices for sampling and to avoid application. Further, a test process for the partial simulation build up of reaction cascade, with which it is possible in vivo response in vitro to fairs.

0007A drawback of the existing methods for sampling, it is that in many cases eg to be hurt the body during tissue sampling. This is with Pain and possibly bleeding (potential risk of infection for the staff) connected. In invasive sampling method, in turn, not all analytical Possibility that currently exist usable. Further, in the sampling changed many biochemical parameters, eg hormone mediator secretion or the disruption of signaling pathways within tissue structures.

0008Compares this situation is even with the applicators. There is the problem, that substances or substance mixtures enter the body and there both can trigger unwanted and unintended reactions. This is especially evident when drugs whose desired effect almost always with unwanted Side effects is accompanied.

0009In allergic diseases, the attending physician would first like to learn which allergens the patient shows an allergic response. however, are as so-called provocation tests Allergens applied eg in the nose by inhalation or support surface on which are the allergens that can directly or of diffusing allergens into the body. This is to the body's Defensive reaction, are in case of a positive allergen determined. unintentionally a Allergenisierung may be but triggered only that is only through the contact with the allergen, which used in the provocation test is a new allergy forms against this same allergen. Further, in the Treatment of allergies applied the so-called desensitization, at the smallest amount of allergens to be administered to the patient. For example, in patent DE 19609315 proposed nasal sampler may create an undesired cause sensitization and thus cause the patient harm.

0010The object of the invention was to minimize or eliminate these disadvantages and yet an advanced for the patient analytically methodical spectrum for to have available. Furthermore, it was the task by the simulation of a part of the natural pathway, the desired test parameters in measurable quantities to to convict without the body reactions in general to influence have to.

Description of the Invention

0011The object is achieved by an apparatus and method, that makes it possible by means of a support surface, one or more coupling surfaces or structures on the nasal mucosa for some finite time to fix can. Here materials, substances or mixtures are chemically covalently or chelate bound on the coupling surface, so that these, under physiological conditions are not removed from the coupling surface or can diffuse. The coupling surface with the bound materials, substances or mixtures by means of a wide-pored gases which executed from various materials can be mounted on the support surface or without gases by suitable methods attached, eg by gluing, welding, clamps, nails, rivets, etc.

0012The support surface itself can be used as clip that pushing outwards or inwards is designed to be (Fig.1) or as a single clip for each nasal wall (Fig.2 / Fig.3).

0013The coupling surface or structure on which the materials, substances or mixtures bound are can be multiple shared or made of one piece. On the Coupling surface or structure may be one or more of each other or separate mixed materials, substances or mixtures to be bound or multiple separate coupling surfaces or structures on the carrier surface be attached (Figure 4).

0014Further, on the support surface of the coupling surface structure or a spacer (Fig.5) in the form of a sponge or fabric of any structure or hardness are applied. Support surface, spacer, coupling surface and

0015Gases can in different materials, shapes are executed. Without the can restrict the claims as an example the design of the form in anatomically nasal adapted type are performed.

0016The total of the support surface with or without a spacer with coupling surface or structure with or without porous gases, the device according to the invention represent (Figure 5).

0017This apparatus is the basis for the inventive method the simulation a pathway and the following analytical steps. The invention The method used is covalently bound or chelated materials, substances or Mixtures of the latter are brought to the nasal mucosa by the support surface the coupling surface or structure pressed to the nasal mucosa. Thus, the Exposure of the nasal mucosa with a simulated fabric. By covalently or chelate binding is prevented that on the coupling surface or structure bonded materials, substances or mixtures in the nasal mucosa and thus may penetrate the body of the patient.

0018As an example which does not limit the patent scope, are the allergic to name diseases. The most common disorder is allergic rhinitis, their reported morbidity in Central Europe with 10 to 20% in the scientific literature becomes. Naturally, meets a toy in the air we breathe to the allergen Nasal mucosa. The elements on the mast cells, including IgE antibodies and other Immunoglobulins recognize or allergens. In the positive case is a Reaction cascade triggered, which then Erkrankungs usual symptoms of a result.

0019The simulator according to the invention has one or more allergens on the coupling surface which contact with the nasal mucosa, has bound. It is the exposure the nasal mucous membrane with an allergen and the binding of the antibody or a cell to the allergen simulated and therefore the main part of the beginning of a allergic cascade that for triggering the symptoms of allergic disease leads.

0020The IgE antibodies or other subclasses of immunoglobulins bind the positive Case to the bound allergens on the coupling surface. Since the antibody according to the bond are also bound to the allergen, they can no longer Signal to start the reaction cascade trigger; the patient remains free of complaint and can not be immunized (allergenisiert). After removal of the support surface of the nasal mucosa, together with the coupling surface, the concentration of the bound IgE antibodies or other Immunsubklassen outside the body the prior art methods are measured in vitro ELISA. The measured concentration of allergen-specific IgE antibodies is an internationally accepted measure for the expression of allergic disease of type-1. Since cells and other immunoglobulin subclasses of the allergens on the bind coupling surface in the positive case, other types of allergic can Diseases are detected.

0021As a further example which does not limit the patent scope also is the follow-up of drug doses in patients. In this case are antibodies to the drug substance or the drug and its metabolites at the coupling surface or structure covalently bonded. If the coupling surface in defined distances by means of the support surfaces according to the invention to the nasal mucosa brought, the specific antibodies or the drug and their metabolites. After removing the coupling face including the bound drug molecules or and their metabolites, pharmacological data as Blood or tissue concentration can be determined temporally resolved, in the classic<i>in vitro</i> analytical methods such as HPLC or GC are applied. In order to the rise in level of drugs or their metabolites may be in storage tissue the body as adipose tissue or muscle tissue to simulate time-resolved manner.

0022The method according to the invention, the whole complex of covalent or chelatartiger Binding of one or more materials, substances or mixtures whose exposure by means of the support surface of the nasal mucosa and the compound of the invention an actual prior art analytical methods represent.