89results about How to "Low dark toxicity" patented technology

The invention discloses a photosensitizer phospholipid compound, a preparation method of the photosensitizer phospholipid compound, a pharmaceutical composition and application of the photosensitizer phospholipid compound. The pharmaceutical composition is the photosensitizer phospholipid or a combined pharmaceutical composition of the photosensitizer phospholipid and a pharmacologically acceptable carrier, and the pharmaceutical composition is in the form of a liquid preparation, a solid preparation, a semisolid preparation, a capsule, granules, a gel or an injection. The photosensitizer phospholipid compound or a liposome of the photosensitizer phospholipid is applicable to the photodynamic therapy of tumors; the photosensitizer phospholipid compound or the liposome of the photosensitizer phospholipid compound can be rapidly taken by cells and can release a photosensitizer crude drug, and under laser action, the photosensitizer phospholipid compound or the liposome of the photosensitizer phospholipid compound can rapidly release active oxygen to take a strong anti-tumor effect. The photosensitizer phospholipid compound and a liposome nanoparticle thereof can serve as a liquid preparation, a solid preparation, a semisolid preparation, a sterilized preparation and a sterile preparation; and the photosensitizer phospholipid compound and the liposome nanoparticle are low in toxicity and are applicable to the efficient treatment of various tumors.

The invention discloses a fullereneporphyrin derivate photosensitizer as well as a preparation method and application thereof. The structural formula of the fullereneporphyrin derivate photosensitizer is shown as the formula I. The fullereneporphyrin derivate photosensitizer can overcome the defect that a traditional photosensitizer needs enough oxygen concentration, and effective reactive oxygen can still be generated under the low oxygen concentration, so that a good treatment effect can be achieved. The fullereneporphyrin derivate photosensitizer has the advantages of high phototoxicity, low dark toxicity, high selectivity in pickup of cancer cells and the like, and has a broad spectrum, a killing effect on cancer cells and a remarkable bacteria killing effect. Most of all, the fullereneporphyrin derivate can be metabolized in a mouse body, and is a novel photosensitizer with a good prospect.

The invention relates to a tyrosine phthalocyanine derivative which has a structural general formula as the right, in the formula, M is equal to Zn or Al, R is equal to H, Na or CH2CH3. The preparation method for the tyrosine phthalocyanine derivative is: (1) an intermediate II is obtained through the reaction of tyrosine and 4-nitrophthalic nitrile with protected amino group; (2) an intermediate III can be obtained by detracting Boc in the solution of dichloromethane and trifluoroacetic acid; (3) the tyrosine phthalocyanine derivative I can be obtained by cyclizing of the dinitriles intermediate that comprises the tyrosine; wherein, the Boc is di-tert-butyl dicarbonate, a DMF is N, N-dimethylformamide, and a DBU is 1,8-diazacyclo(5,4,0)hendecene-7. The invention also comprises the application of the tyrosine phthalocyanine photosensitizers in preparing photodynamic medicines.

The invention relates to a preparation method and application in the preparation of photodynamic therapy medicines of a fat-soluble photosensitizer loaded on inorganic salt carrier or modified surface inorganic salt carrier. The preparation method comprises the following steps: in or without the presence of surfactant, firstly adding distilled water, DMSO solution of fat-soluble photosensitizer, chloride solution and phosphate solution, performing magnetic stirring, and obtaining calcium phosphate nanoparticles with the grain size less than 100nm of fat-soluble photosensitizer after the reaction, wherein the molar ratio of chloride solution to phosphate solution is 1:10-10:1. The preparation method of the invention is simple, is easy to operate and has high stability and low cost; the diameter of the prepared nanoparticles is about 70nm, thus facilitating the preparation and storage of the product; the nanoparticles have high water-solubility and good dispersity, and can be used to promote the effective transmission of the fat-soluble photosensitizer in blood and eliminate the toxic or side effects of the fat-soluble photosensitizer which is used alone; and the nanoparticles have low toxicity in the dark and high phototoxicity.

The invention discloses a preparation method for fat-soluble phtosensitizer nanoparticles. Under the condition that that the potential of hydrogen (pH) value is 1-14, a fat-soluble phtosensitizer or soluble inorganic salt is added into a reaction medium respectively to prepare A and B systems and the A system and the B system are mixed. Or, the fat-soluble phtosensitizer or soluble inorganic salt are simultaneously added into the reaction medium and then mixed. The fat-soluble phtosensitizer self-assembles to form a nanometer structure and the fat-soluble phtosensitizer nanoparticles are obtained after separation and purification. The fat-soluble phtosensitizer nanoparticles prepared by the method provided by the invention has high water-solubility and good dispersibility and can be steadily dispersed in water phase, so that the effective transmission of the fat-soluble phtosensitizer nanoparticles in blood is promoted. Meantime, the method has the advantages of simpleness, easiness in operation, high stability and low cost. The invention also relates to the application of the fat-soluble phtosensitizer nanoparticles prepared by the method in preparing photodynamic therapy medicine.

The invention discloses an iridium complex with a phosphorescent ion pair structure as well as a preparation method and an application of the iridium complex. The iridium complex is a phosphorescent anion and cation type soft salt iridium complex formed by bonding of a terpyridyl cation complex and a cation complex, wherein the cation complex contains a cyclometalated ligand, and a metal center and cyanogen are taken as auxiliary ligands. The structural general formula of the iridium complex is as shown in the specification. The iridium complex with the phosphorescent ion pair structure is capable of generating singlet oxygen under the radiation of white light, can be applied to the photodynamics treatment field and has very good application prospects in the photodynamics treatment.

Asymmetrically substituted metal-phthalocyanine compounds are disclosed. These compounds and other phthalo-cyanine-derivatives are used in bioimaging, bioanalysis, FRET and quenching techniques, photodynamic therapy, DNA analysis for cells, proteins, tissues and other biological entities, and other applications. Near-infrared fluorescence minimizes matrix effects typically seen in other methods of analyzing biochemical entities in cells, proteins, tissues and other biological entities.

The invention discloses a preparing method of soluble bamboo bacterioruberin titanium oxide nanometer particle, which comprises the following steps: hydrolyzing organic titanium compound in the alcohol, acetic acid and distilled water; dripping the alcohol solution of bamboo bacterioruberin slowly; stirring; reacting to add the distilled water; adjusting the pH value of the solution to 7. 0; dialyzing to remove alcohol and small molecular compound; freezing; drying; obtaining the product; setting the weight rate of organic titanium compound and acetic acid at 1: 2-6; setting the weight rate of organic titanium compound and alcohol and distilled water at 1: 10-20: 1-3. The bamboo bacterioruberin is the bamboo bacterioruberin methyl, bamboo bacterioruberin ethyl or derivant of two compounds and the organic titanium compound is titanic acid tetraacetate, titanic acid tetra-n-propyl ester, tetraisopropoxy titanium, titanic acid tetera-n-butoyl or polytitanium acid butoyl. The invention has simple, easy and stable operation with diameter of soluble nanometer particle less than 150nm, which is beneficial to prepare and reserve the product.

The invention belongs to the field of heterocyclic compounds and particularly relates to a chlorophyllin salt compound and a preparation method thereof. The chlorophyllin salt compound is a novel photosensitizer which is stable in nature, high in photodynamic activity, low in skin toxicity and controllable in quality and is used for photodynamic treatment of cancers, infections and other diseasesrequired to be treated by optical radiation. In the invention, the substituent of R3 is inform of a carboxylate, so the water solubility is high and the preparation of subsequent medicinal preparations is promoted; the absorption wavelength is more than 650 nanometers; the quantum yield of triplet state and the quantum yield of low singlet oxygen are high; the toxicity in darkness is low, and health of human body can be improved; the selectivity is high; the structure is clear and the performance is stable; and the fat water compatibility is high.

The invention discloses cationic phthalocyanine. A structural formula is shown in the figure. The cationic phthalocyanine derivative disclosed by the invention has good water solubility and low aggregation degree, has good photosensitive activity and antitumor activity, and is applicable to being used as a photosensitizer for diphtheria / pertussis / tetanus (DPT) treatment. The invention also relates to a preparation method and an application of the cationic phthalocyanine.

The invention discloses a novel metal iridium (III) complex. The chemical structural formula of the metal iridium (III) complex is shown in a formula (I); and the metal iridium (III) complex has no toxicity to tumor cells and normal cells in the dark, but has strong growth inhibition ability to the tumor cells under light conditions, has a photo-catalytic oxidation effect on NADH, and is of greatsignificance to the study of a high-efficiency and low-toxicity iridium complex photosensitizer, anti-tumor drugs can further be prepared, and great application prospects are achieved.

The invention discloses a method for preparing a medicament-nanometer calcium phosphate composite system taking a fat soluble photosensitizer as a framework, which comprises the following steps of: under the condition that phosphoryl-containing organic matters exist or do not exist, adding distilled water and aqueous solution of calcium salt, and stirring uniformly to prepare a system A; adding the distilled water and aqueous solution of phosphate, and stirring uniformly to prepare a system B; and adding fat soluble photosensitizer solution into the system A or the system B or adding the fat soluble photosensitizer solution into the systems A and B simultaneously, stirring uniformly, and mixing the system A and the system B to obtain the medicament-nanometer calcium phosphate composite system taking the fat soluble photosensitizer as the framework. The administration system prepared by the method is high in water solubility and dispersibility and can promote the effective transmission of the fat soluble photosensitizer in blood, and the medicine loading rate of the administration system is increased. Simultaneously, the preparation method is simple, easy to operate, high in stability and low in cost. The invention also relates to application of the administration system prepared by the method in the preparation of medicaments for photodynamic therapy.

Preparation method of water-soluble hypocrelline silica nanoparticle comprises carrying out hydrolysis of single silicane or multiple silicanes to obtain nano-silica with core-shell structure, enveloping hypocrelline under the existence or inexistence of surfactant, dialysing to remove solvent and small moleculal chemical compound, and freeze drying to obtain water-soluble hypocrelline silica nanoparticle with particle diameter less than 150nm suitable for intravenous injection. The invention also provides thr application of the water soluble hypocrelline silica nanoparticle in preparing photodynamic medicinal intravenous injection. The inventive preparation method has simple and easy operation and high product stability. The nanoparticle has good water-solubility and dispersity, low dark toxicity, and high phototoxicity; can not liberate hypocrelline thereby eliminating its photo toxico-adverse side effect. Hypocrellines can gather in intrastitial mitochondrion, effectively improve phototherapy efficiency, and reduce pharmic consumption.

The invention discloses a 2,9,16,23-tetra-((4-aminomethyl) phenoxy) zinc phthalocyanine hydroiodide, as well as a preparation method and application thereof to a photodynamic therapy method, and relates to a 2,9,16,23-tetra-((4-aminomethyl) phenoxy) zinc phthalocyanine hydroiodide photosensitizer. The 2,9,16,23-tetra-((4-aminomethyl) phenoxy) zinc phthalocyanine hydroiodide photosensitizer not only is simple in synthetic method, excellent in solubility (based on the protonation principle) in water, high in anti-tumor activity (based on the heavy atom effect) and low in dark toxicity, but also has a good application prospect in the field of photodynamic therapy methods.

The invention relates to a freeze-dried HPPH powder injection preparation for injection and a preparation method thereof. The freeze-dried powder injection preparation contains HPPH, a cosolvent, a solubilizer, an excipient and a pH regulating agent. The freeze-dried HPPH powder injection preparation prepared in the invention can be used for treating a plurality of solid tumors like the lung cancer, the esophagus cancer, the head, face and neck cancer, the bladder cancer and the stomach cancer, and has the advantages of sponginess, good redissolvability, low moisture content, good stability, low dark toxicity and high photosensitivity.

The invention discloses polyamidoamine-dendrimers (PAMAM-CD) / HP(haematoporphyrin) / ICG(indocyanine green) nanometer medicine with controllable photodynamic treatment effects, and a preparation method thereof. The nanometer medicine is characterized in that the HP and the ICG are coated and loaded into PAMAM-CD; the ICG is used as a switch of the HP; the fluorescence of the HP is quenched by ICG; meanwhile, the photodynamic treatment is switched off. When the nanometer medicine is exposed in 808nm laser, the ICG is decomposed; the HP fluorescence is restored; the photodynamic treatment is opened; meanwhile, the ICG photothermal treatment is accompanied. The medicine solves the problem of dark toxicity of the HP, and also realizes the combination of the controlled photodynamic treatment and the photothermal therapy through the switch effect of the ICG.

The invention relates to a mitochondria-targeting BODIPY compound and a preparation method and application of liposome-coated nanoparticles of the BODIPY compound. The BODIPY compound contains a cationic group which is easily combined with a mitochondrial membrane with negative electricity in cells, so that the BODIPY compound is targeted to mitochondrial organelles of the cells. The BODIPY compound is wrapped by liposome, and liposome nanoparticles with uniform particle size are prepared in an aqueous solution. The nanoparticles have high stability and good biocompatibility in an aqueous solution. After the nanoparticles are taken by tumor cells, the liposome structure is destroyed, and the released BODIPY compound is targeted to cell mitochondria. Besides, under the 665nm illumination condition, active oxygen generated by the BODIPY compound causes oxidative damage to active molecules in mitochondria, so that tumor cells are killed. The liposome nanoparticles can be applied to tumorphotodynamic therapy as a drug for delivering various photosensitizers.

The invention relates to phospham amphipathic phthalocyanine derivatives, a preparation method and application to the preparation of phototherapeutic medicines thereof. A structural general formula of the derivatives is shown as below: wherein p,q=0,1; p+q=1; q=0, p=2; n=1-5; m=0,1; R=Ch3, CH3CH2-, M is Zn or Al, M1 is H or Na. The phospham zwitterion group exists in the molecular structural formula of the phospham amphipathic phthalocyanine derivatives: p, q=0, 1; p+q=1; q=0, p=2; n=1-5; R=CH3, CH3CH2-, M1 is H or Na. The phospham amphipathic phthalocyanine derivatives are applied to the preparation of the phototherapeutic medicines.

The embodiment of the invention discloses a fullerene phthalocyanine derivative as well as a preparation method and application thereof. The fullerene phthalocyanine derivative has the advantages of novel structure, small possibility of generating photobleaching, light degradation and aggregation, high phototoxicity and low dark toxicity and is more stable under an illumination condition.

The invention relates to platinum drugphotosensitizer-loaded protein nanoparticles and a preparation method and application thereof. The platinum drugphotosensitizer-loaded protein nanoparticles comprise platinum drugphotosensitizer complexes and proteins wrapping the platinum drugphotosensitizer complexes. Chemical therapy and photodynamic therapy are combined through an albumin nano-drug delivery system so that a synergistic anti-cancer effect is achieved, and the toxicity-reducing and efficacy-improving treatment effect is achieved. The nanoparticles prepared by the method are small in particle size, uniform in dispersion and round in shape; good chemical stability and illumination stability are realized; under the irradiation of near-infrared light, the nanoparticles have relatively high active oxygen generation capability; in addition, in cell experiments and animal experiments, it is verified that the nanoparticle has strong cytotoxicity and good in-vivo tumor targeting to tumorcells, plays a synergistic effect, reduces toxic and side effects, realizes combined treatment of tumors by chemotherapy and photodynamic therapy, and inhibits tumor metastasis.

The present invention discloses fatty chain end group diamine substituted hypocrellin derivatives, including 2-site amino substituted hypocrellin A, 2-site amino substituted hypocrellin B, and Schiff base formed with hypocrellin A or hypocrellin B with diamine in the site-17. Compared with hypocrellin A and hypocrellin B, the products of the present invention has stronger absorption in phototherapeutic window of 600-900 nm, can produce active oxygen in photosensitive condition, and has powerful photodynamic effect and low dark toxicity. The present invention also discloses the preparation process and the use in preparing medicine for treating cancer and AIDS.

The invention discloses polyamine phthalocyanine and a derivative thereof. The structural general formula of the derivative of polyamine phthalocyanine is shown in descriptions. The derivative of polyamine phthalocyanine, disclosed by the invention, has relatively good solubility and photosensitive activity, has a certain targeting function and is suitable for serving as a photosensitizer for PDT (Photodynamic Therapy). The invention further relates to preparation methods and application of polyamine phthalocyanine and the derivative thereof.

A photosensitizer and derivative, application thereof. The photosensitizer has the structure of general formula I, wherein X is S or Se, Y is organic or inorganic ion, R1 and R2 are independently selected from H, alkyl, alkoxy, alkyl amido, alkyl azide and the like; R3 is selected from H, alkyl, alkoxy, amino sulfonyl, hydroxyl, carboxyl and the like, and L1 is a linker selected from —(CH2)n1— or —(CH2CH2O)n2—. The derivatives are molecular medicines with drug molecules of anticancer and chemotherapy or tumor targeting function connected to the said photosensitizer. The photosensitizer has excellent near infrared characteristics and low dark toxicity and is used in the field of photodynamic tumor therapy. The introduction of benzophenothiazine or benzophenoselenazine into derivatives with tumor-targeting function could improve the specific uptake of photosensitizer in tumor tissues. Moreover, clinical anticancer drugs can be introduced into the structure of benzophenothiazine or benzophenoselenazine to achieve the purpose of combining therapy of photodynamic therapy and chemotherapy.

The invention relates to the technical field of medicine, in particular to a ruthenium coordination compound with near-infrared fluorescence, a preparation method and application thereof. After a chromophore-pyrene is introduced, the coordination compound has obvious phototoxicity (IC50 = 0.040 [mu]M) and small dark toxicity (IC50 = 9.402 [mu]M) when applied to cervical cancer (HeLa cells) under the irradiation of 635 nm red light, the photodynamic therapy index (PI) is 235.05, and the photodynamic therapy has a remarkable curative effect. The ruthenium metal coordination compound can generate singlet oxygen under the irradiation of a 635 nm light source, and can photocatalytically oxidize NADH and NADPH. According to the invention, the ruthenium coordination compound has important significance for promoting the research of a high-efficiency novel anti-tumor ruthenium metal coordination compound photosensitizer, can be further used for preparing anti-tumor drugs, and has a relatively great application prospect.

The invention discloses a D-benzothiadiazole-TB(-D) derivative as well as a synthesis method and application thereof. The structural formula of the D-benzothiadiazole-TB(-D) derivative is shown as a formula I or II. The D-benzothiadiazole-TB(-D) derivative has large Stokes displacement, shows excellent luminescence property, has excellent solid luminescence and has the potential of becoming an excellent OLED (Organic Light Emitting Diode) material. The D-benzothiadiazole-TB(-D) derivative has a wide pH application range and can be applied to a human physiological environment; the D-benzothiadiazole-TB(-D) derivative has effective and good response to viscosity, and has the possibility of becoming a viscosity response fluorescent probe; the D-benzothiadiazole-TB(-D) derivative has recognition capability on Fe<3+> and is expected to become an excellent Fe<3+> fluorescent probe; and the D-benzothiadiazole-TB(-D) derivative has a good PDT effect, can perform dyeing imaging on A549 cells, and expands the variety of photosensitizers.

The invention belongs to the technical field of medicines, and relates to a novel chlorin e4 derivative and pharmaceutically acceptable salts thereof, and preparation methods and application of the novel chlorin e4 derivative and thepharmaceutically acceptable salt thereof. The chlorin e4 derivative comprises a structure shown as a general formula I and an optical isomer contained in the structural general formula I; according to the preparation method, 17-propionyl or 13-formyl in chlorin e4 and amino acid are subjected to peptide formation and / or 3-vinyl etherification. The chlorin e4 derivative and the pharmaceutically acceptable salt thereof can be applied as a photodynamic antitumor drug. Compared with the existing similar photosensitizer talaporfin which is clinically applied, the chlorin e4 derivative disclosed by the invention has the advantages of strong photodynamic antitumor activity, high dark toxicity-light toxicity ratio and the like; the derivative can be used for preparing novel photodynamic antitumor drugs including photodynamic cancer treatment drugs, drugs for photodynamic treatment of benign vascular diseases such as age-related macular degeneration and nevus flammeus and drugs for photodynamic treatment of condyloma acuminata.

The invention discloses application of water-soluble porphyrin in preparing photodynamic therapy medicine. The chemical name of water-soluble porphyrin is tetraiodide 5, 10, 15, 20-tetra {4-[2-(1-methyl-1-piperidine)ethyoxyl][phenyl}porphyrin, water-soluble porphyrin (I) has quite strong recognition effect on G-quadruplex and is high in targeting performance when being applied in photodynamic therapy. TMPipEOPP almost has no cutting activity to G-quadruplex in darkness but presents quite high photosensitive cutting activity to G-quadruplex under light by generating 1O2 and .OH. This shows that TMPipEOPP can serve as a PDT photosensitizer of G-quadruplex under physiological conditions. In addition, cytotoxicity experiments show that TMPipEOOP almost has no dark toxicity or is extremely low in dark toxicity but has quite high photoinduced cytotoxicity, and this also shows that TMPipEOOP is a PDT photosensitizer with quite low dark toxicity.

The invention provides an antagonistic peptide, a copolymer thereof, a nano-assembly as well as preparation methods and applications of the antagonistic peptide, the copolymer and the nano-assembly. The antagonistic peptide is a PD-L1 antagonistic peptide, is named M-APP, and has a structure shown in the specification. The M-APP is used as a raw material to prepare the copolymer IR780-M-APP with aclear structure, the copolymer IR780-M-APP can be self-assembled to form the nano-assembly, so that the problem of poor immunogenicity in immunotherapy is solved, and the utilization rate of the immune antagonistic peptide is improved; and through photodynamic therapy, the problem of poor water solubility of IR780 can be solved, the effect of phototherapy is improved, and the efficacy of immunotherapy is enhanced.

The invention discloses a sorafenib-ruthenium complex as well as a preparation method and application thereof. The sorafenib-ruthenium complex contains cations as shown in a chemical structural formula 1. The preparation method of the sorafenib-ruthenium complex comprises the following steps: dissolving sorafenib and a ruthenium complex in a reaction solvent to prepare a mixed solution; and carrying out a coordination reaction on the mixed solution in a dark and protective atmosphere to generate the sorafenib-ruthenium complex, and the like. The sorafenib-ruthenium complex disclosed by the invention shows low toxicity to Hep-G2 liver tumor cells and normal liver cells in a dark environment; and the toxicity to liver tumor cells is enhanced under the illumination condition, and the compound can be used for photoactivation chemotherapy of tumors and can be applied to preparation of liver cancer targeted drugs.

The invention provides an iridium (III) complex and a preparation method and application thereof. The anti-tumor iridium (III) complex with a structure as shown in a formula (1) or a formula (2) in the invention can specifically target mitochondria or lysosome, has low dark toxicity and high phototoxicity, and has a very high phototoxicity index in tumor cells, particularly in non-small cell lung cancer cells Meanwhile, the anti-tumor metal iridium (III) complex can be used as a photosensitizer to participate in photodynamic therapy. Compared with a traditional photosensitizer, the anti-tumor metal iridium (III) complex has the advantages of being good in water solubility, high in light stability, low in dark toxicity and the like, and can realize integration of diagnosis and treatment.