CN104459099A - Application of porphyrin derivative in preparation of agent for detecting inflammatory disease - Google Patents

Application of porphyrin derivative in preparation of agent for detecting inflammatory disease Download PDF

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Publication number
CN104459099A
CN104459099A CN201410794876.8A CN201410794876A CN104459099A CN 104459099 A CN104459099 A CN 104459099A CN 201410794876 A CN201410794876 A CN 201410794876A CN 104459099 A CN104459099 A CN 104459099A
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porphyrin
application
porphyrin derivative
derivatives
preparation
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CN201410794876.8A
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CN104459099B (en
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王雪梅
赵春秋
李晓琦
吴长宇
任发
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Southeast University
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Southeast University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/10Musculoskeletal or connective tissue disorders
    • G01N2800/101Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
    • G01N2800/102Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints

Abstract

The invention discloses an application of a porphyrin derivative in preparation of an agent for detecting an inflammatory disease. The porphyrin derivative can be tetra-p-sulfophenyl porphyrin. The inflammatory disease refers to rheumatoid arthritis. The porphyrin derivative has stable and good optical and electrochemical properties and excellent biocompatibility, and the optical properties (including ultraviolet-visible absorption spectrum, fluorescence spectrum and the like) and electrochemical properties of the porphyrin derivative can be obviously changed by virtue of metabolites of body fluid or urine of the patients suffering from the related diseases. By utilizing the characteristics, the application of the porphyrin derivative in the preparation of the agent for detecting the inflammatory disease is provided by the invention for the first time, and the novel application of the porphyrin derivative is widened.

Description

Derivatives of porphyrin detects the application in inflammation related disease reagent in preparation
Technical field
The present invention relates to biological chemistry pharmaceutical field, be specifically related to the application of derivatives of porphyrin in preparation detection inflammation related disease (such as rheumatoid arthritis) reagent.
Background technology
As everyone knows, inflammation is very common and important basic pathology process, the trauma infection contamination of body surface and most of common disease of each organ and frequently-occurring disease (as furuncle, carbuncle, pneumonia, hepatitis, ephritis etc.) all belong to diseases associated with inflammation, be there is vascular system biological tissue to the defensive reaction of damage factor, and the metabolic product of many types can be produced in this course accordingly.Rheumatoid arthritis is a kind of chronic systemic autoimmune disease based on arthropathy wherein.The painful swelling of joints of main clinical manifestation caused by Minor articulus synovial membrane, cartilage destruction, joint space narrow then, late period because of serious destruction of bone, absorb cause joint stiffness, deformity, dysfunction.This disease mostly is a kind of repeated relapsing disease, and disability rate is higher, prognosis mala, does not also well effect a radical cure method at present.Control antirheumatic can produce permanent mitigation, delay or stop the deterioration of the state of an illness, anti-inflammatory and antalgesic can alleviate pain and improve stiff, but can not stop the deterioration of the injury in joint or the state of an illness that slows down.Being middle and advanced stage when in most cases Symptoms is obvious, therefore having found a kind of early detection method and perhaps can better effect a radical cure this type of disease, is also the striving direction of future clinical medical treatment early prevention.
Derivatives of porphyrin is divided into fat-soluble porphyrin compound and water-soluble porphyrin compound two kinds usually, and this material has certain photo-sensitive characteristic, under ultraviolet light or visible ray effect, effectively can discharge singlet oxygen.Early stage porphyrin is obtained, as protoheme, chlorophyll etc. from containing the natural products of porphyrin compound by the method such as extracting and developing, purifying.Two kinds of approach are had to obtain target Porphyrin Molecule at present: the structural modification of natural porphyrin and the full synthesis of porphyrin compound.Although the structural modification of natural porphyrin can carry out the transformation of structure easily, be subject to the restriction of structure itself, also very limited in the selection of simultaneously outer shroud functional group, in addition, also limit the physiologically active of porphyrin compound own.Therefore, usual people need the way by entirely synthesizing, and obtain the Porphyrin Molecule with specific physiologically active and function.Four-p-sulfonic group phenyl the porphyrin (TSPP) etc. that the present invention applies, is a class water miscible sulfonic group corproporphyrin derivant, has stable fluorescent characteristic and good biocompatibility.
Summary of the invention
Technical matters solved by the invention is: provide the change of the optics after a kind of derivatives of porphyrin and the effect of inflammation correlative metabolites and electrochemical properties to realize rheumatoid arthritis quick, highly sensitive detection in early days, have wide using value and prospect.
In order to solve the problems of the technologies described above, the technical solution adopted in the present invention is:
Derivatives of porphyrin is detecting the application in inflammation related disease reagent in preparation.
Derivatives of porphyrin described in above-mentioned application is four-p-sulfonic group phenyl porphyrin.
Inflammation related disease described in above-mentioned application is rheumatoid arthritis.
Reagent described in above-mentioned application is derivatives of porphyrin.
Reagent described in above-mentioned application is the composition comprising derivatives of porphyrin.
The invention has the beneficial effects as follows: compared with prior art, advantage of the present invention is as follows:
Because derivatives of porphyrin has stable good optics, electrochemical properties and excellent biocompatibility, and the metabolin in the body fluid of relevant disease or urine can change optical characteristics (comprising ultraviolet-visible absorption spectroscopy and fluorescence spectrum etc.) and the electrochemical properties of derivatives of porphyrin significantly.Utilize this characteristic, the present invention proposes the application of derivatives of porphyrin in preparation detection inflammation related disease reagent first, has expanded the novelty teabag of derivatives of porphyrin.
Accompanying drawing explanation
The ultraviolet-visible absorption spectroscopy of Fig. 1 to be concentration be TSPP of 0.01mg/ml
Fig. 2 is for adopting derivatives of porphyrin of the present invention---control group and experimental group ultraviolet and visible absorption peak peak change comparison diagram in the experiment of TSPP detection type rheumatic arthritis
Embodiment
Below in conjunction with Figure of description, the present invention is further illustrated
Because four-p-sulfonic group phenyl porphyrin (TSPP) has with the similar porphyrin ring texture of most derivatives of porphyrin and sulfonic group, and the albumen etc. in the correlative metabolites detected is easy to same porphyrin ring structure and sulfonic group combines, coordination, thus change optics and the electrochemical properties of derivatives of porphyrin, following embodiment is described the application that derivatives of porphyrin detects in inflammation related disease reagent in preparation for four-p-sulfonic group phenyl porphyrin (TSPP), the derivatives of porphyrin of other similar can be applied to the preparation detecting inflammation related disease reagent too.
In following embodiment, the body fluid (as blood) of normal empirical model group or urine take from normal male DBA/1 mouse or other Normal groups; The body fluid of inflammation related disease empirical model group or urine take from the male DBA/1 mouse of collagen-induced early stage CIA or other inflammation related disease empirical model groups.
Below in conjunction with specific embodiment, set forth the present invention further.
Embodiment 1: utilize the inflammation correlative metabolites such as TSPP optical characteristics detection type rheumatic arthritis, concrete steps are as follows:
1 utilizes ultraviolet-visible pectrophotometer and fluorospectrophotometer to characterize optics (ultraviolet-visible absorption spectroscopy and the fluorescence spectrum) characteristic of TSPP (0.01mg/ml), obtains the ultraviolet and visible absorption peak peak A of titer TSPP (0.01mg/ml) tSPP(as shown in Figure 1) the fluorescence emission peak peak I and by 515nm excitation obtained tSPP.
2 get the body fluid of normal empirical model group or the body fluid of urine and inflammation related disease empirical model group or each 10 μ l of urine, drip TSPP (0.01mg/ml) titer respectively, utilize ultraviolet-visible pectrophotometer and fluorospectrophotometer to characterize optics (ultraviolet-visible absorption spectroscopy and the fluorescence spectrum) characteristic of mixed solution, obtain the ultraviolet and visible absorption peak peak A of each mixed solution uNand by the fluorescence emission peak peak I that 515nm excitation obtains uN, calculate titer TSPP (0.01mg/ml) and normal changing value Δ A=A between empirical model group and inflammation related disease empirical model group respectively tSPP-A uNand Δ I=I tSPP-I uN.
3 testing result displays: the ultraviolet and visible absorption peak peak change Δ A of normal empirical model group nORand fluorescence emission peak peak change Δ I nORbe far smaller than inflammation related disease empirical model group ultraviolet and visible absorption peak peak change Δ A iLLand fluorescence emission peak peak change Δ I iLL.
Embodiment 2: utilize the inflammation correlative metabolites such as TSPP electrochemical properties detection type rheumatic arthritis, concrete steps are as follows:
1 utilizes electrochemical workstation to characterize the electrochemical properties of TSPP titer (0.01mg/ml), obtains the galvanochemistry differential pulse voltammetry curve (DPV of titer tSPP) and some galvanochemistry peaks of correspondence.
2 get the body fluid of normal empirical model group or the body fluid of urine and inflammation related disease empirical model group or each 10 μ l of urine, drip TSPP (0.01mg/ml) titer respectively, utilize electrochemical workstation to characterize the electrochemical properties of above-mentioned mixed solution, obtain the galvanochemistry differential pulse voltammetry curve (DPV of each mixed solution nORand DPV iLL) and some galvanochemistry peaks of correspondence.3 found that, the DPV of normal empirical model group nORwith the DPV of titer tSPPwithout obviously difference, corresponding galvanochemistry peak position and peak value are without significant change; And the DPV of inflammation related disease empirical model group iLLwith the DPV of titer tSPPobvious difference, corresponding many galvanochemistry peaks are owing to adding the body fluid of inflammation related disease empirical model group or urine and to disappear or peak value diminishes.
Shown by above instantiation result: the derivatives of porphyrin that this method adopts has good optical characteristics and electrochemical properties, and the body fluid of inflammation disease animal pattern and patient or urine can change optical characteristics (comprising uv-vis spectra and fluorescence spectrum etc.) and the electrochemical properties of derivatives of porphyrin significantly.The good characteristic that this method takes full advantage of derivatives of porphyrin and the impact produced inflammation disease body fluid and urine thereof, simple and easy to do, quick, high specificity, has wide clinical medicine using value and prospect.
More than show and describe ultimate principle of the present invention and principal character and advantage of the present invention.The technician of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and instructions just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.

Claims (5)

1. derivatives of porphyrin detects the application in inflammation related disease reagent in preparation.
2. apply according to claim 1, it is characterized in that described derivatives of porphyrin is four-p-sulfonic group phenyl porphyrin.
3. apply according to claim 1, it is characterized in that described inflammation related disease is rheumatoid arthritis.
4. application according to claim 1, is characterized in that: described reagent is derivatives of porphyrin.
5. application according to claim 1, is characterized in that: described reagent is the composition comprising derivatives of porphyrin.
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