CN112022815A - Water phase preparation high Cu (DTC)2Method for preparing anti-tumor protein nano medicine with medicine loading capacity - Google Patents
Water phase preparation high Cu (DTC)2Method for preparing anti-tumor protein nano medicine with medicine loading capacity Download PDFInfo
- Publication number
- CN112022815A CN112022815A CN202010836824.8A CN202010836824A CN112022815A CN 112022815 A CN112022815 A CN 112022815A CN 202010836824 A CN202010836824 A CN 202010836824A CN 112022815 A CN112022815 A CN 112022815A
- Authority
- CN
- China
- Prior art keywords
- dtc
- drug
- protein
- preparing
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/325—Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Nanotechnology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Crystallography & Structural Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Manufacturing & Machinery (AREA)
- General Physics & Mathematics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Physics & Mathematics (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a method for preparing high Cu (DTC) by using a water phase2A method for preparing a drug-loading anti-tumor protein nano-drug. The method comprises the following steps: (1) dissolving protein in deionized water, adding water-soluble copper salt while stirring, and adjusting the pH of the solution to be strong alkaline; (2) adding a newly prepared NaDTC aqueous solution into the solution obtained in the step (1) under stirring, and continuously stirring until the reaction is finished; (3) dialyzing the solution reacted in the step (2), and passing the solution after the dialysis is finishedFiltering to remove insoluble substance, and freeze drying to obtain Cu (DTC)2Protein nanoparticles. The invention utilizes Cu2+Rapid reaction with DTC in water to generate Cu (DTC) in situ on the surface of the protein2Thereby obtaining Cu (DTC) simply and quickly2Protein nanoparticles; the preparation process does not need to use an organic solvent, is green and environment-friendly, is simple to operate, and can be repeatedly produced in large dose; moreover, the nanoparticles Cu (DTC) prepared by the invention2The drug loading is high, close to 25 wt%, and simultaneously, the in vitro cytotoxicity is higher than that of a free drug Cu (DTC)2。
Description
Technical Field
The invention relates to a high Cu (DTC)2A method for preparing a drug-loaded protein nano-drug, in particular to a method for preparing high Cu (DTC) by using a water phase2A method for loading drug protein nano-drugs, belonging to the technical field of pharmaceutical preparations.
Background
Cu(DTC)2Chinese characters are named as N, N-diethyl dithiocarbamate, British name is copper disulfide, also abbreviated as Cu (DDC)2CuET, and the like. Cu (DTC)2Is prepared from disulfiram and Cu2+The reaction-generated metal organic complex shows excellent chemotherapeutic effect on various cancers such as melanoma, non-small cell lung cancer, breast cancer and the like (Alcohol-use drug targets cancer via 97 segregant adaptor NPL4.Nature 2017,552(7684), 194-. However, Cu (DTC)2Being insoluble in water, solubilization by the nanoformulations and improving their bioavailability are key to achieving their chemotherapeutic effect.
The protein is a biological macromolecule, has good biological safety, and can be used as a natural nano carrier of a hydrophobic drug. Chinese invention patent (publication No. CN201310151359.4) discloses Cu (DTC) for injection2A process for the preparation of nanoparticle formulations, but which requires the use of organic solvents such as methanol, ethanol and the like to dissolve Cu (DTC)2And the prepared protein nanoparticles Cu (DTC)2The drug loading was only 10%.
Disclosure of Invention
The purpose of the invention is as follows: for existing Cu (DTC)2The preparation process of the protein nano preparation needs to use an organic solvent, and the preparation Cu (DTC)2The invention provides a method for preparing high Cu (DTC) by using an aqueous phase without using an organic solvent2A method for loading drug protein nano-drugs.
The technical scheme is as follows: the invention relates to a method for preparing high Cu (DTC) by using water phase2The method for loading the drug-loading protein nano-drug comprises the following steps:
(1) dissolving protein in deionized water, adding water-soluble copper salt while stirring, and adjusting the pH of the solution to be strong alkaline;
(2) adding a newly prepared NaDTC aqueous solution into the solution obtained in the step (1) under stirring, and continuously stirring until the reaction is finished;
(3) dialyzing the solution reacted in the step (2), filtering to remove insoluble substances after dialysis, and freeze-drying to obtain Cu (DTC)2Protein nanoparticles.
In the step (1), the protein can be at least one of human serum albumin, bovine serum albumin, transferrin, horseradish peroxidase and the like; the concentration of the solution of the protein dissolved in the deionized water is preferably 10-100 mg/mL. The water-soluble copper salt can be at least one of copper chloride, copper sulfate, copper acetate, copper nitrate, etc.; cu in water-soluble copper salt2+The concentration of (B) is preferably 0.1 to 0.5 mol/L. Wherein, the dosage of the protein and the water-soluble copper salt satisfies the following relation: adding 0.02-0.4 millimole of copper ions into every 250mg of protein. In the step, the pH value of the solution is adjusted to be strong alkali, so that high drug loading capacity can be guaranteed, and the pH value of the solution can be preferably adjusted to be 11-13.
In the step (2), the concentration of the newly prepared NaDTC aqueous solution is preferably 0.1-0.5 mol/L. The addition amount of the NaDTC aqueous solution meets the following proportion: in the reaction system, the molar ratio of the copper ions to the DTC is 1: 0.5-1: 20.
The drug loading rate can be effectively controlled by regulating the ratio of the protein to the copper ions, preferably, when the dosage of the protein and the water-soluble copper salt satisfies the following relationship that the molar ratio of the copper ions to the DTC is 1: 2-1: 20, and in a reaction system, the molar ratio of the copper ions to the DTC is 1: 2-1: 20, Cu (DTC) with higher drug loading rate can be obtained2Protein nanoparticles.
In step (3), a dialysis processThe method specifically comprises the following steps: and (3) transferring the solution reacted in the step (2) into a dialysis bag for dialysis for 12-72 hours, wherein an external medium is ultrapure water. The residual water-soluble inorganic small molecules such as NaOH, NaDTC and the like in the system can be removed through dialysis, so that the purity of the nano-drug is ensured, and OH is not contained-And the like toxic substances; the dialysis time can be determined according to the time frequency of changing the dialysis medium.
Has the advantages that: compared with the prior art, the invention has the advantages that: (1) the invention prepares Cu (DTC)2Is dissolved in an aqueous solution of a protein in advance, and then Cu is used2+Rapid reaction with DTC in water to generate Cu (DTC) in situ on the surface of the protein2Thereby obtaining Cu (DTC) simply and quickly2Protein nanoparticles; compared with the prior art, the method has the advantages that the finished product Cu (DTC)2Compared with the preparation process of dissolving in an organic solvent and combining the organic solvent with a protein carrier, the preparation process of the invention does not need to use the organic solvent, is green and environment-friendly, has simple operation and can realize large-dose repeated production; (2) the nano-particle Cu (DTC) prepared by the invention2The drug loading is high, close to 25 wt%, and the drug loading is easy to regulate and control; at the same time, its cytotoxicity in vitro is higher than that of the free drug Cu (DTC)2The bioavailability of the free medicine can be improved; (3) the raw materials used by the invention have low price, the encapsulation rate is close to 100 percent, and a great amount of chemotherapeutic drugs Cu (DTC) can not be caused2Is wasted.
Drawings
FIG. 1 shows Cu (DTC) prepared in example 12Transmission electron microscopy images of albumin nanoparticles;
FIG. 2 shows Cu (DTC) prepared in example 12Ultraviolet absorption spectrogram of albumin nanoparticles;
FIG. 3 shows Cu (DTC) prepared in example 12Inhibition of the growth curve of B16 cancer cells in vitro by albumin nanoparticles.
Detailed Description
The technical solution of the present invention is further explained with reference to the drawings and the embodiments.
Example 1
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and added successively under stirring1.0mL of CuCl2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 4mL NaDTC aqueous solution (0.2mol/L) with stirring, stirring for 1 hour, transferring into a dialysis bag with cut-off molecular weight of 10000 Da, and dialyzing for 24 hours, wherein the external medium is ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The transmission electron microscope picture of the bovine serum albumin nanoparticles is shown in figure 1, and the particle size range is 25-43 nm.
Freeze-drying Cu (DTC)2Bovine serum albumin nanoparticles were re-dissolved in water at a nanoparticle concentration of 0.5mg/mL and their UV absorption in water is shown in FIG. 2, which shows Cu (DTC)2And (6) successfully loading. Further test of Cu (DTC)2The drug loading of the bovine serum albumin nanoparticles is as follows: determination of the UV absorbance of the nanoparticles in acetonitrile according to Cu (DTC)2Drug loading was calculated as 24.3% on a standard curve in acetonitrile.
Results of nanoparticle in vitro inhibition of 4T1 mouse breast cancer cells FIG. 3, where Cu (DTC)2The bovine serum albumin nano-particle has higher drug availability than the free drug Cu (DTC)2Has enhanced anticancer activity.
Example 2
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added in this order with stirring2Aqueous solution (0.02mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 4mL NaDTC aqueous solution (0.02mol/L) with stirring, stirring for 1 hour, transferring into a dialysis bag with cut-off molecular weight of 10000 Da, and dialyzing for 24 hours, wherein the external medium is ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2Bovine serum albumin nanoparticles with the particle size range of 20-45 nm and the drug loading rate of 2.8 percent.
Example 3
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added in this order with stirring2Aqueous solution (0.1mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 4mL NaDTC aqueous solution (0.1mol/L) under stirring, stirring for 1 hr, transferring into dialysis bag with cut-off molecular weight of 10000 DaDialyzing for 24 hours, and taking ultrapure water as an external medium. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The bovine serum albumin nanoparticles have the particle size of 25-40 nm and the drug loading rate of 11.2%.
Example 4
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added in this order with stirring2Aqueous solution (0.4mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 4mL NaDTC aqueous solution (0.2mol/L) with stirring, stirring for 1 hour, transferring into a dialysis bag with cut-off molecular weight of 10000 Da, and dialyzing for 24 hours, wherein the external medium is ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The bovine serum albumin nanoparticles have the particle size of 27-38 nm and the drug loading rate of 25.0%.
Example 5
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and 1mL of CuCl was added in order with stirring2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 0.5mL NaDTC aqueous solution (0.2mol/L) with stirring, stirring for 1 hr, transferring into dialysis bag with cut-off molecular weight of 10000 Da, and dialyzing for 24 hr with ultrapure water as external medium. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The bovine serum albumin nanoparticles have the particle size of 20-58 nm and the drug loading rate of 8.4%.
Example 6
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added in this order with stirring2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Adding 10mL NaDTC aqueous solution (0.4mol/L) while stirring, transferring into a dialysis bag with cut-off molecular weight of 10000 Da for dialysis for 24 hours after stirring for 1 hour, wherein the external medium is ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The bovine serum albumin nanoparticles have the particle size of 24-56 nm and the drug loading rate of 23.7%.
Example 7
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added in this order with stirring2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Fresh 4mL of NaDTC aqueous solution (0.2mol/L) was added with stirring, and after stirring for 1 hour, the mixture was transferred to a dialysis bag with a cut-off molecular weight of 10000 Da for dialysis for 12 hours, and the external medium was ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The bovine serum albumin nanoparticles have the particle size of 25-55 nm and the drug loading rate of 24.1%.
Example 8
250mg of Bovine Serum Albumin (BSA) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added in this order with stirring2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Fresh 4mL of NaDTC aqueous solution (0.2mol/L) was added with stirring, and after stirring for 1 hour, the mixture was transferred to a dialysis bag with a cut-off molecular weight of 10000 Da for dialysis for 72 hours, and the external medium was ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The bovine serum albumin nanoparticles have the particle size of 25-48 nm and the drug loading rate of 23.8%.
Example 9
250mg of Human Serum Albumin (HSA) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added in order with stirring2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 4mL NaDTC aqueous solution (0.2mol/L) with stirring, stirring for 1 hour, transferring into a dialysis bag with cut-off molecular weight of 10000 Da, and dialyzing for 24 hours, wherein the external medium is ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The human serum albumin nanoparticles have the particle size of 25-45 nm and the drug loading rate of 23.8%.
Example 10
250mg Transferrin (TRP) was dissolved in 10mL deionized water, and 1.0mL CuCl was added sequentially with stirring2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 4mL NaDTC aqueous solution (0.2mol/L) with stirring, stirring for 1 hour, transferring into a dialysis bag with cut-off molecular weight of 10000 Da, and dialyzing for 24 hours, wherein the external medium is ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The particle size of the transferrin nano particle is 27-51 nm, and the drug loading rate is 22.5％。
Example 11
250mg of horseradish peroxidase (HRP) was dissolved in 10mL of deionized water, and 1.0mL of CuCl was added sequentially with stirring2Aqueous solution (0.2mol/L), 0.5mL NaOH solution (1 mol/L). Adding fresh 4mL NaDTC aqueous solution (0.2mol/L) with stirring, stirring for 1 hour, transferring into a dialysis bag with cut-off molecular weight of 10000 Da, and dialyzing for 24 hours, wherein the external medium is ultrapure water. After the completion of dialysis, insoluble matter was removed by filtration, and the filtrate was lyophilized to obtain Cu (DTC)2The particle size of the transferrin nanoparticles is 31-55 nm, and the drug loading rate is 21.8%.
Claims (9)
1. Water phase preparation high Cu (DTC)2The method for preparing the drug-loading anti-tumor protein nano-drug is characterized by comprising the following steps:
(1) dissolving protein in deionized water, adding water-soluble copper salt while stirring, and adjusting the pH of the solution to be strong alkaline;
(2) adding a newly prepared NaDTC aqueous solution into the solution obtained in the step (1) under stirring, and continuously stirring until the reaction is finished;
(3) dialyzing the solution reacted in the step (2), filtering to remove insoluble substances after dialysis, and freeze-drying to obtain Cu (DTC)2Protein nanoparticles.
2. Aqueous phase preparation high Cu (DTC) according to claim 12The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that in the step (1), the protein is at least one of human serum albumin, bovine serum albumin, transferrin and horse radish peroxidase.
3. Aqueous phase preparation high Cu (DTC) according to claim 12The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that in the step (1), the dosage of the protein and the water-soluble copper salt satisfies the following relation: adding 0.02-0.4 millimole of copper ions into every 250mg of protein.
4. According to the rightAqueous phase preparation of high Cu (DTC) according to claim 32The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that the dosage of the protein and the water-soluble copper salt satisfies the following relation: adding 0.2-0.4 millimole of copper ions into every 250mg of protein.
5. Aqueous phase preparation high Cu (DTC) according to claim 12The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that in the step (1), the pH value of a solution is adjusted to 11-13.
6. Aqueous phase preparation high Cu (DTC) according to claim 12The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that in the step (1), the water-soluble copper salt is at least one of copper chloride, copper sulfate, copper acetate and copper nitrate.
7. Aqueous phase preparation high Cu (DTC) according to claim 12The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that in the step (2), the molar ratio of copper ions to DTC in a reaction system is 1: 0.5-1: 20.
8. Aqueous phase preparation high Cu (DTC) according to claim 72The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that the molar ratio of copper ions to DTC in a reaction system is 1: 2-1: 20.
9. Aqueous phase preparation high Cu (DTC) according to claim 12The method for preparing the drug-loading anti-tumor protein nano-drug is characterized in that in the step (3), the dialysis is as follows: and (3) transferring the solution reacted in the step (2) into a dialysis bag for dialysis for 12-72 hours, wherein an external medium is ultrapure water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010836824.8A CN112022815B (en) | 2020-08-19 | 2020-08-19 | Aqueous phase preparation of high Cu content (DTC)2Method for loading anti-tumor protein nano-drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010836824.8A CN112022815B (en) | 2020-08-19 | 2020-08-19 | Aqueous phase preparation of high Cu content (DTC)2Method for loading anti-tumor protein nano-drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112022815A true CN112022815A (en) | 2020-12-04 |
| CN112022815B CN112022815B (en) | 2022-05-10 |
Family
ID=73578534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010836824.8A Active CN112022815B (en) | 2020-08-19 | 2020-08-19 | Aqueous phase preparation of high Cu content (DTC)2Method for loading anti-tumor protein nano-drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112022815B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070232692A1 (en) * | 1998-09-08 | 2007-10-04 | The University Of Utah | Method of Treating Cancer Using Dithiocarbamate Derivatives |
| CN103222961A (en) * | 2013-04-26 | 2013-07-31 | 沈阳药科大学 | Injection Cu(DDC)2 protein nano-particle preparation used for treating tumor, and preparation method thereof |
| CN111467492A (en) * | 2020-05-20 | 2020-07-31 | 中国科学院生态环境研究中心 | Copper compound-based intelligent nano material, and preparation method and anti-tumor application thereof |
-
2020
- 2020-08-19 CN CN202010836824.8A patent/CN112022815B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070232692A1 (en) * | 1998-09-08 | 2007-10-04 | The University Of Utah | Method of Treating Cancer Using Dithiocarbamate Derivatives |
| CN103222961A (en) * | 2013-04-26 | 2013-07-31 | 沈阳药科大学 | Injection Cu(DDC)2 protein nano-particle preparation used for treating tumor, and preparation method thereof |
| CN111467492A (en) * | 2020-05-20 | 2020-07-31 | 中国科学院生态环境研究中心 | Copper compound-based intelligent nano material, and preparation method and anti-tumor application thereof |
Non-Patent Citations (1)
| Title |
|---|
| LI XIAO ET AL.,: "Apoferritin as a Carrier of Cu(II) Diethyldithiocarbamate and Biomedical Application for Glutathione-Responsive Combination Chemotherapy", 《ACS APPL. BIO MATER》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112022815B (en) | 2022-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111012760B (en) | Casein/anionic polysaccharide nano particle loaded with hydrophobic drug and nutrient and preparation method thereof | |
| CN108704144B (en) | Method for synthesizing gold nanorod-based hybrid nanogel through polypeptide self-assembly | |
| CN109054000B (en) | Nano drug-loading system based on polysalicylic acid and preparation method and application thereof | |
| CN102349871B (en) | Nano-micro drug delivery system and preparation method of 10-hydroxyl camptothecin | |
| Jiang et al. | Preparation, physicochemical characterization, and cytotoxicity of selenium nanoparticles stabilized by Oudemansiella raphanipies polysaccharide | |
| CN115919801A (en) | Preparation method of tannin-zinc coordinated chitosan-selenium nanoparticles | |
| CN112022815B (en) | Aqueous phase preparation of high Cu content (DTC)2Method for loading anti-tumor protein nano-drug | |
| CA2709267C (en) | Drug delivery system for administration of a water soluble, cationic and amphiphilic pharmaceutically active substance | |
| CN113181199B (en) | PH-responsive intelligent porous magnetic nano drug delivery system for combined administration of bicalutamide and adriamycin and preparation method thereof | |
| CN107929261B (en) | pH-sensitive targeted nanoparticle preparation loaded with chemotherapeutic drugs and preparation method thereof | |
| US11684572B2 (en) | Methods for producing carboxylate ligand modified ferric iron hydroxide colloids and related compositions and uses | |
| CN110448549B (en) | Nano material self-assembled by metformin hydrochloride and 7-ethyl-10-hydroxycamptothecin | |
| CN109662955B (en) | Oleanolic acid grafted chitosan drug-loaded nanoparticle and preparation and application thereof | |
| CN105418804B (en) | Low anticoagulant property heparin of a kind of hydrophobization and its preparation method and application | |
| CN103432083A (en) | Preparation process for glycyrrhizic acid-mediated hydroxycamptothecine albumin liver cancer targeting nanoparticle lyophilized powder | |
| CN109276720B (en) | Metal-organic complex nano material and preparation method and application thereof | |
| CN110787303A (en) | Pt-SR adduct of Pt and mercapto compound, preparation and application | |
| CN117427037B (en) | Tripterine-copper ion ligand nano-particle and preparation method and application thereof | |
| CN110538164A (en) | PH-sensitive hydroxyapatite/zein nano-drug carrier and application thereof | |
| CN111039821B (en) | Phosphate-stabilized niclosamide nanocrystal and preparation method and application thereof | |
| KR101817992B1 (en) | Deselenide compound and oxidation-seneitive particle comprising the same and method for preparing the same | |
| CN113476475B (en) | Zinc salicylate nanoparticles and preparation method and application thereof | |
| CN114177307B (en) | Preparation method of transferrin modified paclitaxel coix seed oil nanoemulsion with active targeting function | |
| CN109893498A (en) | A kind of preparation and application of docetaxel micella-gel | |
| CN114569554A (en) | Tumor-targeting triptolide emulsion and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |