# US 2013/0156827 A1 · Sodium alginate crosslinked slow-release moxifloxacin microsphere, the preparation method and the use thereof, and target vascular occlusive agent of the microsphere

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2013/0156827 A1
- Document ID: US20130156827A1
- Status: Published application
- Kind: A1
- Application number: 13/809,361
- Filed: 2010-12-30
- Published: 2013-06-20
- Earliest claimed: 2010-07-09
- Assignees: Beijing Shengyiyao Technology & Development Co., Ltd.
- Inventors: Xinjian Li; Hong Hong
- Web page: https://patentgrep.com/patent/US20130156827A1

## CPC

- A61K 9/1658: {Proteins, e.g. albumin, gelatin}
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/1682: {Processes}
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61P 31/06: for tuberculosis
- C07D 471/04: Ortho-condensed systems
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

A sodium alginate crosslinked slow-released moxifloxacin microsphere, the preparation method of the microsphere, a vascular target embolus containing the microsphere and the use of the microsphere in preparing the vascular target embolus. The microsphere contains moxifloxacin, a drug carrier, a adsorbent, a reinforcing agent and a solidifying agent, wherein the drug carrier is sodium alginate, the adsorbent is albumin prepared from human plasma or bovine serum albumin, the reinforcing agent is gelatin or hyaluronic acid, and the solidifying agent is a divalent metal cation chosen from calcium salt or barium salt.

## Claims

### Claim 1

A sodium alginate crosslinked moxifloxacin sustained-release microsphere, comprising: a drug carrier, adsorbent, anti-tuberculosis drug active ingredient, strengthening agent and curing agent, wherein the carrier is sodium alginate, the adsorbent is human serum albumin or bovine serum albumin, the anti-tuberculosis drug active ingredient is moxifloxacin, the strengthening agent is gelatin or hyaluronic acid, and the curing agent is a salt of divalent metal cation.

### Claim 2 (depends on 1)

The sustained-release microsphere according to claim 1, wherein when the microsphere is preserved in vegetable oil or liquid paraffin as a preservation solution, the particle size of the microsphere is in the range of 50˜100 μm, 50˜150 μm, 50˜200 μm, 100˜300 μm, 150˜450 μm, 300˜500 μm, 500˜700 μm, 700˜900 μm or 900˜1,250 μm.

### Claim 3 (depends on 1)

The sustained-release microsphere according to claim 1, wherein the microsphere is a dry powdered particle with particle size in the range of 10˜50 μm, 25˜50 μm, 50˜100 μm, 100˜350 μm, 300˜550 μm or 500˜750 μm.

### Claim 4 (depends on 1)

The sustained-release microsphere according to claim 1, wherein the weight ratio of sodium alginate and moxifloxacin is 1˜75:0.25˜12.5.

### Claim 5 (depends on 1)

A method for preparing the sustained-release microsphere according to claim 1, comprising the following steps:
1) dissolving sodium alginate with physiological saline or water for injection based on mass-volume percentage of 0.5˜15% to obtain a sodium alginate solution as a carrier solution;
2) dissolving human serum albumin or bovine serum albumin with water for injection based on mass-volume percentage of 0.1˜10% to obtain a albumin solution as an adsorbent;
3) grinding, stirring, dissolving and adsorbing moxifloxacin with the adsorbent prepared in step 2) to obtain a moxifloxacin solution as a drug solution, wherein moxifloxacin and the adsorbent are added in an amount of mass-volume percentage of 1.6˜4%;
4) preparing an aqueous solution of 1˜15% by mass-volume with a salt of divalent metal cation to obtain a curing solution;
5) adding anhydrous ethanol and water for injection into the resulting curing solution, wherein the volume ratio of the resulting curing solution, anhydrous ethanol and water for injection is 2:1:2, so that a curing solution containing anhydrous ethanol is obtained;
6) dissolving gelatin or hyaluronic acid with water for injection to obtain a gelatin or hyaluronic acid solution of 0.1˜10% by mass-volume as a strengthening solution;
7) pooling the drug solution and the carrier solution at a volume ratio of 1:1˜30, and magnetically stirring the solution uniformly to obtain a preparing solution;
8) spraying the above-obtained preparing solution by a high voltage electrostatic multi-head microsphere generating device to obtain droplets which are then dispersed in the curing solution, and removing supernatant when precipitation is completed , to obtain sodium alginate crosslinked microspheres or micro-gel beads containing moxifloxacin; and
9) adding the above-obtained microspheres or micro-gel beads into the strengthening solution, stirring the solution, and discarding supernatant to obtain microspheres or micro-gel beads containing drug as sodium alginate crosslinked moxifloxacin sustained-release microspheres.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the microspheres or micro-gel beads containing drug obtained in step 9) are preserved in vegetable oil or liquid paraffin oil.

### Claim 7 (depends on 5)

The method according to claim 5, wherein the calcium salt is selected from calcium chloride or calcium lactate, and the barium salt is barium chloride.

### Claim 8 (depends on 5)

The method according to claim 5, wherein the high voltage electrostatic multi-head microsphere generating device used in step 8) comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, a plurality of positive and negative electrodes, sterile syringes of various models and a lifting device, wherein the high voltage electrostatic generating device is provided with the plurality of positive and negative electrodes, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to a stainless steel wire immersed in the curing solution, the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.

### Claim 9 (depends on 1)

A vascular targeted embolic agent containing the sustained-release microsphere according to claim 1.

### Claim 10 (depends on 1)

A use of the microsphere according to claim 1 in preparing a vascular targeted embolic agent.

### Claim 11 (depends on 10)

The use according to claim 10, wherein the vascular targeted embolic agent is used for treating tuberculosis.

### Claim 12 (depends on 10)

The use according to claim 10, wherein the vascular targeted embolic agent is used for treating renal tuberculosis, thyroid tuberculosis, cervical lymph node tuberculosis, pericardial tuberculosis, chest wall tuberculosis and/or pleural tuberculosis.

### Claim 13 (depends on 10)

The use according to claim 10, wherein the vascular targeted embolic agent is used for treating fallopian tube tuberculosis, endometrium tuberculosis, testis tuberculosis or epididymis tuberculosis.

### Claim 14 (depends on 10)

The use according to claim 10, wherein the vascular targeted embolic agent is used for treating pulmonary tuberculosis, mass hemoptysis of pulmonary tuberculosis or pulmonary tuberculosis cavity through interventional embolization.

### Claim 15 (depends on 1)

The sustained-release microsphere according to claim 1, wherein the curing agent is a divalent calcium or barium salt.

### Claim 16 (depends on 5)

The method according to claim 5, wherein the preparing of the aqueous solution in step 4) comprises preparing the aqueous solution of 1˜15% by mass-volume with a divalent calcium or barium salt to obtain the curing solution.

### Claim 17 (depends on 6)

The method according to claim 6, wherein the high voltage electrostatic multi-head microsphere generating device used in step 8) comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, a plurality of positive and negative electrodes, sterile syringes of various models and a lifting device, wherein the high voltage electrostatic generating device is provided with the plurality of positive and negative electrodes, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to a stainless steel wire immersed in the curing solution, the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.

### Claim 18 (depends on 7)

The method according to claim 7, wherein the high voltage electrostatic multi-head microsphere generating device used in step 8) comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, a plurality of positive and negative electrodes, sterile syringes of various models and a lifting device, wherein the high voltage electrostatic generating device is provided with the plurality of positive and negative electrodes, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to a stainless steel wire immersed in the curing solution, the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.

### Claim 19 (depends on 2)

A vascular targeted embolic agent containing the sustained-release microsphere according to claim 2.

### Claim 20 (depends on 3)

A vascular targeted embolic agent containing the sustained-release microsphere according to claim 3.

### Claim 21 (depends on 4)

A vascular targeted embolic agent containing the sustained-release microsphere according to claim 4.