阅读说明：本技术 使用两种材料的组合遮蔽和随后可视化esr信号 (Masking and subsequent visualization of ESR signals using a combination of two materials ) 是由 N·温德哈伯 A·卡劳 P·霍利格 B·哈特维格 J·柳比纳 于 2018-11-23 设计创作，主要内容包括：本发明涉及具有多个相的物体,所述多个相具有不同的电子自旋共振谱,其不是由每个相单个的ESR谱的简单组合产生的。(The present invention relates to an object having a plurality of phases with different electron spin resonance spectra that do not result from a simple combination of the ESR spectra of each phase individually.)

1. An object having a plurality of phases, which is ingested by or within a human or animal organism,

it is characterized in that

The object has at least two phases having different electron spin resonance spectra.

2. An object according to claim 1, wherein

At least one phase has a purely paramagnetic center, preferably an S radical, which is preferably selected from ultramarine.

3. An object according to claim 1 or 2, wherein

At least one phase has at least one collective order state selected from ferromagnetic, ferrimagnetic and/or antiferromagnetic, preferably selected from iron-oxygen compounds, more preferably magnetite or a material with an Fe-O phase.

4. Object according to at least one of the preceding claims, wherein at least one phase is encapsulated by at least one other phase.

5. Object according to at least one of the preceding claims, wherein at least two phases are present in mixed form.

6. An object according to claim 1, wherein

The object has at least three phases, one of which is preferably paramagnetic, preferably selected from (phen) CuCl₂。

7. Object according to any one of the preceding claims, wherein at least one phase comprises at least one medically-technical polymer with paramagnetic centers, preferably isolated radicals.

8. Use of an object according to any of claims 1 to 7, wherein the obtained ESR spectrum is stored in a data storage means, and the stored data is preferably transmitted to a receiving means upon receipt of a demand signal.

9. Use according to claim 8 in a data management network.

10. Use according to claim 8 or 9 in fingerprinting, in copyright protection and/or in nutrition.

11. Use of an object according to the invention according to claim 1 having at least three phases for monitoring a decomposition process in a human or animal organism.

Technical Field

The invention relates to an object having a plurality of phasesThe plurality of phases have different electron spin resonance spectra.

Background

Systems with cyclic magnetic properties are known in great detail in the prior art, in which charged electrons exhibit spontaneous magnetic sequences and which are clearly distinguished from those in which the magnetic sequence is caused by localized electron spins. The latter is important in chemical complexing atoms, especially almost all colored minerals, often as industrial fillers and pigments or rare earth elements. Other important paramagnetic centers are insulators, such as synthetic and natural polymers and organic dyes, such as quinones, anthocyanins and polyphenols.

However, the magnetic moment of localized electron spins is also increasingly affected by the spin-orbit coupling effect in the main and sub-groups as the atomic number of the chemical element, which is the trunk atom corresponding to the localized electron spins, increases. Material scientists therefore also know microscopic and macroscopic spin-lattice systems up to metallic conductors.

If the above-mentioned systems, i.e. ion-atom, chemical complex, insulator-radical such as polymer, mineral-inerted or natural mineral, semimetal or metal systems, are irradiated with microwaves, different steady-state or dynamic electron spin resonance spectra are obtained in the most general sense, wherein the term "electron spin resonance" is abbreviated in the present invention to "ESR".

In principle only systems with unpaired electrons are available for ESR spectroscopy, such as free radical systems, paramagnetic transition metals, ribbon magnets and semiconductors. Angelika Bruckner in chem. Ing. Tech.2014,86,11, p 1871-1882 suggests that, depending on the system, the resonant electron spins may undergo complex interactions, for example between electron and nuclear spins, and/or be affected by spatial symmetry. This results in a complex ESR spectrum that is often not easily interpretable when measuring systems consisting of multiple superimposed components. Although this demonstrates the high potential of this spectroscopy method for studying unpaired electron systems, it can be seen at the same time that the combination of various systems cannot be easily attributed to a linear or easily calculated combination of ESR spectra.

If the problem of tracking a given substance on its way through the human or animal organism is now posed, the challenge is that the position, identity and change over time of the ESR spectrum must be detected very accurately to be able to draw conclusions therefrom about the physical and/or chemical conversion of the aggregate or the substance, for example during dissolution in the course of digestion or in other processes of its metabolism.

Dorfman, j.exp.theor.phys.48(1965),715 evaluated how macroscopic magnetic observables in these systems were in principle dependent on grain size. In general, the behavior of the spin systems, the "probes" for bending the total aggregates of moments and the applicability of legal regulations in the materials relevant here, in particular in medical-technical preparations, is therefore difficult to predict.

The intensity of the ESR signal, corresponding to the integral of the absorption signal, and the spontaneous magnetization M of the sample, as described in papers b.heinrich and j.f.cochran in Advances in Physics 42(1993),523_sIs in direct proportion. The line width of the ESR signal follows the correlation of the following form

ΔH～K₁/M_s

Wherein K₁Is the magnetocrystalline anisotropy constant; see ya.g. dorfman, j.exp.theor.phys.48(1965), 715.

The magnetic shape anisotropy also has a significant effect on the shape and position of the ESR signal. Since the magnetocrystalline anisotropy constant of known ferromagnetic or ferrimagnetic materials is 10³-10⁶J/m³In accordance with the range of (1), ESR line width was observed

ΔH～(10²…10⁴)Oe

V.K.Sharma and F.Waldner J.appl.Phys.48(1977),4298 observed a ferrimagnetic Fe at room temperature of-1000 Oe₃O₄Line width Δ H in the powder. It should be noted that the magnetocrystalline anisotropy constant of magnetite is about 3 x 10⁴J/m³。

It is also known that in particles equal to or below the critical dimension, thermal fluctuations dominate the magnetocrystalline anisotropy at the critical temperature, also called the blocking temperature, and these particles therefore exhibit superparamagnetic behaviour. In contrast, below the blocking temperature, the particles have a ferromagnetic or ferrimagnetic behavior. The critical dimension of the particles is determined by the magnetocrystalline anisotropy. In magnetite, the critical particle size is about 14 nm; see G.Vallejo-Fernandez et al, J.Phys.D: appl.Phys.46(2013), 312001. Magnetite nanoparticles having a particle size equal to or below 14nm may have relatively narrow ESR lines characteristic of paramagnetic and superparamagnetic particles, as discussed in paper j.non-crystalloid Solids 354(2008),5207 and r.berger, j.magn.magn.mater.234(2001),535 of j.salado et al.

One particular form of such measurements is the detection of paramagnetic effects on imaging nuclear spin tomography, but their measurements are based on much weaker nuclear spin interactions.

Disclosure of Invention

The inventors of the present invention have quite unexpectedly discovered another, quite different, correlation.

The ESR spectrum is considered in the state of knowledge to be typical for irradiated substances, and the problem to be solved is therefore how to provide, in particular by means of the combination of the various systems successfully used here, for example in the form of mixtures, compounds or compositions in general, composed of various macroscopic or microscopic phases, an ESR spectrum characteristic for each composition, a controlled and predictable transformation process on the system of the substance.

It has been found that a composition consisting of at least two materials, at least one of which produces, outside the composition, a characteristic ESR spectrum in its pure form. But in combination with at least one other material, this ESR spectrum surprisingly decays significantly or disappears completely.

The subject of the invention is therefore an object having multiple phases and being ingested or within the organism of a human or animal, characterized in that said object has at least two phases having different electron spin resonance spectra. The subject matter has the advantage that its essential functions are not limited physiologically or controversially toxicologically by the radiation or toxicity of the material.

At least one of said phases advantageously has a cyclic or localized magnetic property. It has been found that the ESR spectrum of rare earth elements is suppressed less well, wherein the object according to the invention exhibits a decay of the ESR spectrum or a superposition of different ESR spectra, depending on the combination.

It may be advantageous that at least one phase of the object according to the invention has a purely paramagnetic center, preferably an S radical, which is preferably selected from ultramarine. It may be particularly advantageous to select superparamagnetic particles instead of ultramarine, which preferably comprise or consist of magnetite or maghemite or pyrite or iron-containing compounds such as amethyst. In the case of these particles, a similar ESR signal was found.

Preferably, at least one phase of the object according to the invention has at least one collective order state, which may be ferromagnetic, ferrimagnetic and/or antiferromagnetic. More preferably, this phase comprises an iron-oxygen compound. Most preferably, at least one phase is magnetite or a phase consisting of an Fe-O system. The phases mentioned are in particular substances which are harmless to human or animal organisms. Furthermore, the phases thus selected may be in the form of tablets. Surprisingly, the effect of ESR spectra is reduced or suppressed by an order of magnitude.

These phases can additionally be readjusted in the particle dispersion. It is therefore possible, again surprisingly, to provide pharmaceutical preparations in a simple manner, since magnetite or a material having an Fe — O phase has very good compatibility with the human organism and is extremely safe to use even in human medicine. The object according to the invention can thus also be used reliably in the gastrointestinal region, since the object does not comprise any highly toxic substances or harmful free radicals.

The invention therefore also provides the use of an object according to the invention, wherein the ESR spectrum is stored in a data storage means, and the stored data is preferably transmitted to a receiving means upon receipt of a demand signal. Thus, further use in a data management network is advantageous.

A particularly advantageous use is in fingerprint profiling, in copyright protection and/or in nutrition.

In any spectroscopy, the better the signal-to-noise ratio of the system in question, in this case the organism in question with the object according to the invention and the instrument for detecting ESR spectra, the better the measurement results achieved. Human and animal organisms exhibit largely diamagnetic behavior in magnetic fields, and the diamagnetic background itself hardly interferes with much more sensitive nuclear spin tomography. Therefore, when using the object according to the invention, only a very low magnetic field strength is required for the measurement of the ESR spectrum.

Furthermore, it may be advantageous that in the object according to the invention at least one phase is encapsulated by at least one other phase. More preferably, one phase encapsulates the other phase as a thin layer.

Preferably, the film and phase thicknesses are selected so that the ESR spectrum of the inner, encapsulated phase is completely obscured by the ESR spectrum of the outer, encapsulated phase.

If the passage of an object according to the invention through the human or animal organism is associated with a decomposition of this object, the ESR signal of the encapsulated phase appears increasingly stronger with the decomposition of the encapsulated phase in a time-dependent manner. This simple time dependence is another advantageous property of the object.

If magnetite particles are selected in at least one phase of the object, the inventors believe, without being bound to a particular theory, that the ESR spectrum may be caused not only by intrinsic magnetism, but also by dipole interactions between the magnetite particles. The interaction is preferably influenced by the shape of the particles, e.g. spheres, needles, cubes and usually by the spatial distribution of the magnetite, e.g. the membrane. These shapes exhibit different demagnetizing fields.

The more ferrimagnetic or ferromagnetic components an object according to the invention possesses, the stronger the attenuation of the ESR signal. In this connection, it is assumed that the absorption of the microwave irradiated in the energy spectrometry is used.

Objects are also conceivable in which the ferromagnetic phase and the radical phase, for example the ultramarine phase, are present spatially separated, preferably in the form of spatially separated agglomerates. This corresponds to a clearly sharp ESR spectrum. If the object subsequently decomposes, the two phases are briefly mixed and, at a suitable quantitative ratio of one phase to the other, the ESR spectrum of one phase, preferably the ultramarine phase, is temporarily completely disappeared. The decomposition of the object in the organism can therefore be specified specifically as a decomposition process.

It may also be advantageous for the object according to the invention to have at least three phases, one of which is preferably paramagnetic, preferably selected from (phen) CuCl₂。

In this case, the ESR is more linear and acquires a time-resolved behavior in the decomposition of the phase mixture, for example when the object is decomposed in metabolic processes in the organism, which is demonstrated by the time dependence of the ESR spectrum. The decomposition in progress can be recorded.

Accordingly, it is preferable that the magnetic phase, the paramagnetic phase and the radical phase be combined. If an object of this composition decomposes in an organism, a further, so-called "final" ESR profile arises, which is clearly different from the ESR profile of the non-decomposed object according to the invention, with the disappearance of the magnetic phase determined by the decomposition or its detachment from the object.

Such a breakdown process is advantageous in the case of non-therapeutic procedures, for example within the scope of inquiry of individuals of nutritional or nutritional habits, non-medical motivations.

However, the disintegration process is also the object of, for example, medical implants, in the functional coating thereof, in particular oral administration forms of nutritional, dietetic or therapeutic preparations, such as capsules, tablets, films and granules and multiparticulate administration forms in the food technology and independently thereof. They can be designed very specifically by the choice of the excipients used, for example the capsule shell, the particle coating and the medical-technical materials used, and are therefore controlled by the formulation process. The solubility of these adjuvants and excipients is preferably used here, more preferably the pH-dependent and time-dependent solubility. In the case of medical-technical implants, hydrolysis in particular leads to the desired absorption of the substrate and the coating. Examples include approved materials and polymers for surgical materialsMethacrylic acid esters andpolyesters, modified starches such as HMPC, HMPC-AS or polylactide (polylactate) and Co-glycolide (Co-glycolide) or Co-caprolactone, and resorbable medical technology coatings or implants. Such insulator polymers, in particular medical polymers, may in this case have paramagnetic centers themselves, which are produced, for example, when irradiated with electron beam or gamma radiation for sterilization. It is therefore further preferred that the object according to the invention has at least one phase containing at least one medically relevant polymer with paramagnetic centers, preferably isolated free radicals.

It is therefore possible to consider the appearance of the final ESR line as a fingerprint of the object during its decomposition in the organism. This is illustrated in more detail in example 2 and fig. 3.

Since the mixed phase is thus distinguishable from the pure phase or the elimination of at least one phase of the object according to the invention is detectable, it is also possible to detect dosage forms in organisms, i.e. mixtures of differently constructed objects.

The invention therefore likewise provides for the use of an object according to the invention having at least three phases for monitoring a decomposition process in a human or animal organism.

The present invention is explained in detail by examples below.

In the present invention, the term "room temperature" is understood to mean an ambient temperature of 20 ℃.

Example 1. objects of the invention comprising ultramarine blue and magnetite.

Magnetite Fe₃O₄Powders (abbreviated as "MAG" in the present invention, under the trade name "Catheay Black B2310", available from Catheay Industries) and ultramarine blue powders (abbreviated as "UB" or "ultramarine", under the trade name "KremerPigment, product number 45000") were mixed using a mortar and a pestle in a weight ratio of MAG: UB ═ 1:30, 3:30 and 4: 30.

The ESR spectrum of the mixture thus obtained is recorded in the X band (9.5GHz) at room temperature and under a microwave energy of 6.3mW, at a modulation frequency of 100kHz and an amplitude of at most 5 Gauss.

Furthermore, a thin layer containing MAG (in which the concentration of MAG is additionally diluted with methylcellulose) or UB is applied in each case to the different tapes, wherein these components are each provided beforehand in the form of a suspension in ethanol.

The ESR spectrum of the layer thus obtained was recorded.

To ascertain that UB and MAG are in intimate contact such that an event with S occurs₃ ^-The ESR spectrum was first recorded on a thin layer alone, with sufficiently large interactions of the free radicals. The ESR spectra were then obtained in each case for the tapes bonded to one another.

FIG. 1a shows ESR spectra of various mixtures of MAG and UB.

At a mixing ratio of UB: MAG of 30:1 on a weight basis, S₃ ^-The ESR signal for free radicals is still well visible at g ═ 2.026. It can be concluded therefrom that not all S of the UB₃ ^-The radicals have undergone a strong magnetic dipole interaction with the MAG. However, even with an increased MAG content corresponding to a mixing ratio by weight of UB: MAG 30:3, a clearly broad ESR signal is already obtained at g 2.307 due to the ferrimagnetic MAG particles. In contrast, due to MAG and S₃ ^-Strong magnetic interaction between free radicals, S₃ ^-The signal of the free radicals is hardly still visible. This effect is further enhanced by increasing the weight ratio of MAG to a ratio UB: MAG of 30: 4.

These line profiles are shown by the graph in FIG. 1b with respect to the applied magnetic field H used for the spectroscopy_applThe second derivative of (a). The line pattern of these second order differentials shows the radical signal more clearly here, especially in the case of a UB: MAG ratio of 30: 4.

The effect of the magnetic interaction between MAG and UB, which increases with the MAG content, becomes perceptible in the respective peak-to-peak distances in the second derivative line profile with respect to the magnetic field.

FIG. 2 shows the ESR spectra obtained for the UB and MAG thin layers on the tape.

As expected, the ESR signal of the layer containing MAG or the layer containing UB coincides with the ESR signal of the pure MAG or UB components.

However, if a close joint is provided by sticking the tapes to each other, a different ESR signal is obtained.

Found by S₃ ^-The ESR signal of MAG loses little strength, but for this reason a slight shift occurs from a value of g-2.766 to g-2.897.

It is speculated that this effect may be due to the magnetic dipole interaction between MAG and UB, which presumably means that the mechanical contact of the thin layer on the tape has even affected S simultaneously₃ ^-ESR signal of free radicals and ferromagnetic ESR signal.

The ESR spectra just confirmed show that even a MAG proportion of about 10% by weight in the mixture of UB and MAG is sufficient to convert S to₃ ^-The ESR signal of the free radical is suppressed below the detection limit. Contact of the thin layer containing both components attenuates the signal even to about half the value.

In contrast, if only the paramagnetic component is mixed with the UB, S₃ ^-The free radical ESR signal is obtained in an almost invariant form, more precisely even if the ratio of paramagnetic components is much higher than MAG.

Without being bound to a particular theory, the inventors of the present invention speculate that the cause of the ESR signal displacement in FIG. 2 is the magnetic state of the particles, which causes self-demagnetization. The obtained internal field H can be approximated by a simple relational expression_int：

H_int＝H_appl–N M,

Where M is the magnetization, N is the degaussing factor, and H_applIs an externally applied magnetic field for this spectroscopy. Degaussing depends on the geometry of the M-containing particles or substances and the overall form of the object composed of such particles or substances. In the layer form, for example, which produces the energy spectrum in fig. 2, it was found that the demagnetization field is significantly stronger than that brought about by spherical or cuboidal particles or objects when an external magnetic field is applied perpendicularly to the layer surface. Here, it is assumed that N is close to 1.

In the case of spherical or cubic particles or objects which are not arranged as layers in particular, N may be set to ≈ 1/3. It is also presumed that the demagnetizing field causes a shift in ESR spectrum by a change in magnetostatic interaction when layers containing magnetite and ultramarine are stacked on each other, as compared with the above-described dipole interaction in the case where magnetite and ultramarine are mixed together.