WO2010124654A1

WO2010124654A1 - Vascular embolus of sodium alginate microspheres comprising drug for resisting hemangioma, preparation method, and use thereof

Info

Publication number: WO2010124654A1
Application number: PCT/CN2010/072386
Authority: WO
Inventors: 李新建; 鲁格; 洪宏
Original assignee: 北京圣医耀科技发展有限责任公司
Priority date: 2009-04-30
Filing date: 2010-04-30
Publication date: 2010-11-04
Also published as: CN101536987A

Abstract

A vascular embolus of sodium alginate microspheres comprising drug for resisting hemangioma, the preparation method, and the use thereof are disclosed. Said micropheres comprise sodium alginate and drug for resisting hemangioma. The weight ratio of sodium alginate to drug for resisting hemangioma is 5:1 - 60:1, wherein said drug is selected from Pingyangmycin, Sodium Morrhuate, Urea, or Bleomycin. Said preparation method comprises: (a) preparing the solution of drug for resisting hemangioma and the solution of sodium alginate respectively; (b) mixing the solution of drug for resisting hemangioma with the solution of sodium alginate; (c) reacting the obtained solution mixture in the fixing solution through the high pressure static microsphere generating device to obtain the vascular embolus of sodium alginate microspheres.

Description

Anti-angioma drug alginate microsphere blood vessel embolization agent, preparation method and application thereof

Technical field

The invention relates to a drug-containing alginate microsphere blood vessel embolization agent, a preparation method and application thereof, and particularly an anti-angioma drug (pingyangmycin, urea, sodium cod liver oil, bleomycin) alginate microsphere blood vessel embolization agent And its preparation method and application.

Background technique

Hemangiomas are the most common benign tumors in humans, and hepatic hemangioma is one of the most common benign liver tumors. More common in adults, more women than men, small tumors are asymptomatic early, often found in physical examination, but with the expansion of the extent of the disease, clinically often abdominal pain, abdominal distension, liver enlargement, abdominal mass, gastrointestinal Symptoms such as oppression, and the risk of spontaneous and traumatic rupture. Once the hemangioma is ruptured, its massive bleeding can be fatal. Therefore, for patients with hepatic hemangioma, the diameter of the tumor is more than 5 cm, or the tumor is located under the liver capsule and advocates active treatment to control its development.

Hemangiomas are also one of the common benign tumors in soft tissues. Benign tumors or congenital malformations often invade facial skin, eyes, nose, lips, tongue, pharynx, soft palate and other organs, causing facial deformities and dysfunction, accounting for benign tumors in children. 36%, and hemangioma in the oral and maxillofacial region accounts for about 60% of the whole body, and can be secondary infection and bleeding, etc., is one of the important diseases that endanger human physical and mental health.

There are many treatments for hemangioma. Although there are different degrees of positive treatment, there are still many problems. For example, surgical treatment often requires tissue transplantation and there are a lot of risk factors for bleeding. Radiation therapy may cause radiation dermatitis and bone tissue damage. The possibility of secondary malignant transformation after irradiation; corticosteroids have a good effect on children's growth and long-term hemangioma, but may be complicated by Cushing's syndrome, affecting development; frozen, laser treatment of superficial hemangioma is better, but for spongy and mixed Hemangioma is poorly treated, and has the disadvantages of ulceration, scarring and pigmentation. There are many types of hardeners. Traditional hardeners such as trichloroacetic acid and absolute ethanol have been used as the first choice for clinical use, but there are injection hardeners. Significant pain, reactive edema, and concurrent tissue necrosis and scar formation are severely limited in pediatric applications. With the development of interventional medicine, interventional embolization has become a hot research topic. Conventional iodized oil and penemycin injection emulsion embolization, tumor area iodized oil can not stay to form tumor embolism, antibiotics can not be effective for a long time, the effect is often not ideal. Therefore, it is necessary to seek a new preparation, a new method for hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other parts of the hemangioma to achieve minimally invasive (non-invasive) Effective treatment.

The use of anticancer drugs (hardeners) for the treatment of hemangioma has been reported in various countries in the 1960s and 1980s. Pingyangcin (PYM) is a broad-spectrum anticancer antibiotic produced by Pingyang streptomycin. The main component is Bleomycin A5 can inhibit the release of thymidine into DNA to release free nucleobase and decompose and destroy it, thereby inhibiting DNA synthesis and cutting DNA strands, interfering with cell division and reproduction, affecting cell metabolism and promoting cell changes. Necrosis. It is a new type of anti-tumor drug that is safer, has fewer side effects, and has no harm to the functions of the hematopoietic system and immune system. Pingyangmycin (PYM) produces free radicals (OFR) during DNA degradation. The effect of OFR on hemangioma can be manifested in: (1) damage to endothelial cells, and OFR covalently binds to enzymes and receptors on the cell membrane. Thereby affecting the structure and function and activity of the membrane, causing the peroxidation of unsaturated fatty acids in the membrane phospholipids to directly affect the membrane structure, peroxides such as malondialdehyde, adversely affecting membrane activity, cross-linking, structural function, and membrane The pores are enlarged and the permeability is increased. (2) Degradation of hyaluronic acid, collagen basement membrane components and cell matrix, destroying the integrity of the blood vessel wall, causing extravasation of plasma components, and edema; (3) stimulating release of endothelin from vascular endothelial cells Active substances; (4) After the endothelial cells are damaged, the super-factor can be released, the neutrophils are attached to the blood vessel wall, and the lysate and OFR are released, thereby aggravating and amplifying the damage benefit; (5) OFR can activate the platelet aggregate, Start blood clotting and form a blood clot. Through the above mechanism, PYM causes vascular endothelial cells to edema, degeneration, hyperplasia, aseptic inflammation, vasoconstriction, thickening of the blood vessel wall, and finally vascular occlusion, atrophy, and lack of blood supply, thereby causing the hemangioma to subside.

Urea, sodium cod liver oil is a human-compatible substance, has no toxic side effects on the human body, especially for large-area hemangioma, high-dose application without adverse reactions, and urea can also change the histomorphology of hemangioma endothelial cells. To achieve the purpose of treatment, the hemangioendothelial cells can be aseptically inflammatory, the enzyme metabolism of the cells is disordered, the dystrophic and shrinking, the cytoplasmic mitochondria are enlarged, the ridge is broken, the collagen fibers are swollen, the crack is broken, and the vascular endothelial cells are necrotic. .

The concept of chemoembolization was proposed by Kato Tetsuo in 1981 as a method of intimate arterial infusion and embolization of a chemotherapy drug. Due to the emergence of modern technologies in interventional medicine, patients have more choices in the process of diagnosis and treatment, and intervention in minimally invasive treatment plays a greater role. Drug microspheres provide new therapeutic ideas through transcatheter arterial embolization.

At present, sodium alginate has not been used as a drug carrier to encapsulate microspheres containing anti-angioma (hardener) drugs and applied to hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, and surface hemangioma. A precedent for interventional embolization therapy for uterine fibroids and other hemangioma.

Technical solution

One of the objects of the present invention is to provide a microsphere which has good biocompatibility, small toxic and side effects, and has dual therapeutic effects of embolization and drug, which can change its absorption distribution in the body and can guide the concentration of the drug around the tumor cells. A microsphere embolization agent that reduces the number of administrations, reduces the pain and burden of the patient, reduces the systemic side effects of the chemotherapeutic drug, and exerts the optimal therapeutic effect against the hemangioma drug.

One of the objects of the present invention is achieved by the following technical solutions:

An alginate microsphere vascular embolization agent containing an anti-angioma drug, comprising: a drug carrier sodium alginate and an anti-angioma drug, the sodium alginate encapsulating the anti-angioma drug.

The weight ratio of the sodium alginate to the anti-angioma drug is from 5:1 to 60:1.

The anti-angioma drugs include pingyangmycin, urea, sodium cod liver oil, bleomycin and the like.

The alginate microsphere vascular embolization agent containing an anti-angioma drug may be a microsphere (microbead) stored in a preservation solution.

The alginate microsphere vascular embolization agent containing an anti-angioma drug may also be a powdery particle.

The microspheres (microbeads) stored in the preservation solution have a particle size ranging from 20 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, 700 to 900 μm, and 900 to 900 nm. Between 1200μm.

The powdery fine particles have a particle diameter ranging from 10 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, and 700 to 900 μm.

Another object of the present invention is to provide a method for preparing a sodium alginate microsphere vascular embolization agent containing the above anti-angioma drug (pingyangmycin, urea, sodium cod liver oil, bleomycin).

The above object of the present invention is achieved by the following technical solutions:

A method for preparing a sodium alginate microsphere vascular embolization agent containing an anti-angioma drug, the steps of which are as follows:

(1) 1 part by weight of an anti-angioma drug (pingyangmycin, urea, sodium cod liver oil, bleomycin) is weighed and dissolved in water for injection; different anti-angioma drug solutions are obtained;

(2) weighing 5 parts by weight to 60 parts by weight of sodium alginate, dissolved in water for injection to obtain a sodium alginate solution;

(3) weighing 2 parts by weight to 12 parts by weight of calcium chloride or cerium chloride, and dissolving in water for injection to obtain a solidifying liquid;

(4) mixing the anti-angioma drug solution obtained in the step (1) and the sodium alginate solution obtained in the step (2), and then reacting with the solidified liquid through a high-voltage electrostatic generating device to solidify into a circular or round-shaped micro. The ball (micro-beads) is obtained by a sodium alginate microsphere vascular embolization agent containing an anti-angioma drug.

The high-voltage electrostatic microsphere generating device comprises: an electrostatic generating device, a mixer, a peristaltic accelerator, a lifting platform, a sterile glass container, a syringe, a special needle connected to the positive and negative poles, and the positive electrode is connected to the needle of the injection device on the peristaltic accelerator, The negative electrode is connected to a stainless steel steel ring in the solidified liquid immersed in a sterile glass container, and the injection device contains a mixed solution of an anti-angioma drug and sodium alginate, and the spray is dropped into the solidified liquid to form a microsphere. .

A preferred technical solution is characterized in that the anti-angioma drug-containing alginate microsphere vascular embolization agent is stored in liquid paraffin or vegetable oil for use, and the anti-angioma drug is kept out of the air.

The obtained alginate microsphere vascular embolization agent containing an anti-angioma drug is a microsphere stored in a preservation solution, which is called a wet bulb. The particle size range may be 20 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, 700 to 900 μm, and 900 to 1200 μm.

After decanting the obtained alginate microsphere vascular embolization agent containing anti-angioma drug, the following microspheres are mixed with an appropriate amount of mannitol solution, frozen in a low temperature refrigerator for more than 2 hours, and then placed in a freeze dryer. The powdery particles are obtained by freeze-drying for 15-48 hours. Or put it in an oven to dry, to obtain powdery particles, called dry balls. The particle diameter may be in the range of 10 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, and 700 to 900 μm.

A third object of the present invention is to provide a method for applying the above-described alginate microsphere vascular embolization agent containing an anti-angioma drug (pingyangmycin, urea, sodium cod liver oil, bleomycin).

The alginate microsphere vascular embolization agent containing anti-angioma drugs (pingyangmycin, urea, sodium cod liver oil, bleomycin) as a treatment for hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma , embolization agents for surface hemangioma, uterine fibroids and other hemangioma drugs.

The specific application steps are as follows: the anti-angioma drug-containing alginate microsphere vascular embolization agent is superselectively embolized into the blood vessel of the lesion by catheter under monitoring of the imaging device (eg hepatic hemangioma, maxillofacial hemangioma) , nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other parts of hemangioma). It can also be used for various types of large thromboembolism to stop bleeding.

Using interventional or interventional ultrasound, the catheter was introduced through the femoral artery, inserted into the blood supply artery of the target organ, and angiography was performed. After the location, size, number and blood supply of the hemangioma were confirmed, the embolization microsphere was selected according to the angiography. diameter of. Use microcatheters as much as possible for superselective embolization, and use aseptically. After opening the bottle cap and standing still, use a syringe to remove the maintenance solution from the bottle and rinse the microspheres three times with the same amount of normal saline or remove the maintenance solution from the bottle and add the same amount of normal saline, together with normal saline and microspheres. Pour into a sterile bowl, rinse the microspheres with 50-60ml saline, discard the rinse solution, add appropriate amount or diluted contrast agent (to fully suspend the microspheres in the contrast agent), and see through the catheter under fluoroscopy The specific situation is slow or slow multiple injections, until the contrast agent flow rate is significantly slowed down, that is, the embolization is completed. The angiography was performed again to determine the embolization effect.

If the alginate microsphere vascular embolization agent containing the anti-angioma drug is a powdery granule, the dry ball stored in the closed container is first dissolved in physiological saline to reduce (wet ball), and then the appropriate amount or diluted angiography is added. The agent is evenly mixed (so that the microspheres are fully suspended in the contrast agent), and then super-selectively embolized by the catheter under the monitoring of the imaging device to slowly or slowly inject into the blood vessel of the lesion site, until the contrast agent flow rate is significantly slowed down, that is, Complete the embolization. The angiography was performed again to determine the embolization effect.

Beneficial effect

The invention adopts a biocompatible, non-toxic and side effect, biodegradable sodium alginate as a carrier of anti-angioma drugs, and prepares anti-hemangioma drug microspheres with different particle diameters, which are controlled release, targeted, and positioned. A new embolic agent for medicine. The drug is embedded in the inside of the microsphere, and the microspheres are injected into the artery to change the absorption distribution in the body, especially when the microsphere is modified to have a certain affinity for the tumor tissue, and the drug can be guided. Concentrated around the tumor cells, on the one hand, the blood vessels at the tumor site are embolized, so as to cut off the blood nutrient supply of the tumor cells, and immediately give a dose of the drug, which reduces the number of administrations, reduces the pain and burden of the patient, and is superior to the conventional perfusion. On the other hand, the drug is lysed by microspheres, and is slowly positioned and released around the tumor tissue, thereby reducing the systemic toxic and side effects of the chemotherapeutic drug, so that the antitumor drug exerts the best therapeutic effect.

Embodiments of the invention

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.

Example 1

Preparation of sodium alginate microspheres containing pingyangmycin

1. Preparation before the parcel:

1 glassware treatment:

The cleaned glassware is dried and placed in a high temperature oven for 3 hours at 280 ° C (sterilization to remove heat);

2 Preparation of anti-angioma drug pingyangmycin liquid:

Weigh 10 g of commercially available pingyangmycin, placed in the above glassware, and dissolved in water to obtain a pingyangmycin drug solution;

3 Preparation of sodium alginate solution:

Weigh 50 grams of commercially available sodium alginate, place it in a glassware, and add physiological saline while stirring until all the sodium alginate is dissolved to obtain a sodium alginate solution;

4 Weigh 2 grams of calcium chloride, dissolved in water for injection, to prepare a 1% by weight calcium chloride solution;

5 formulating liquid paraffin or vegetable oil as a preservation solution;

6 mixing the above pingyangmycin solution and sodium alginate solution to obtain a mixed solution of sodium alginate containing pingyangmycin;

7 Aspirating the above mixture solution with a sterile syringe, passing through a high-voltage electrostatic microsphere generating device, setting various parameters, and dropping into the calcium chloride solution to obtain a wet sodium microalgae containing pingyangmycin. The particle size of the microspheres can be made into wet spheres or dry spheres of different size ranges as needed. For example, 20 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, 700 to 900 μm, and 900 to 1200 μm.

The supernatant solution of the above container was decanted, washed twice with physiological saline, and used immediately.

The upper layer solution of the above container may also be decanted, and the underlying microbeads may be freeze-dried or placed in an oven to dry, and the obtained dry microspheres are sealed and stored.

It is reduced to a wet bulb by soaking in physiological saline before use.

For patients with hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other hemangioma, interventional or interventional ultrasound, transfemoral (maxillofacial) The carotid artery was introduced into the catheter, inserted into the blood supply artery of the target organ, and angiography was performed. After the location, size, number and blood supply of the hemangioma were confirmed, the diameter of the embolization microsphere was determined according to the angiography. Use microcatheters as much as possible for superselective embolization, and use aseptically. The pingyangmycin-containing alginate microspheres (wet bulbs) are pumped with a syringe to remove the preservation solution in the bottle, and the microspheres are washed three times with an equal amount of physiological saline, or the preservation solution and the microspheres in the bottle are poured. In a sterile bowl, rinse the microspheres with 50-60ml saline to discard the rinse solution, then add the appropriate amount or diluted contrast medium (so that the microspheres are fully suspended in the contrast agent), and see through the catheter under fluoroscopy. The lesion is injected slowly or slowly multiple times until the contrast agent flow rate is significantly slowed down, ie the embolization is completed. The angiography was performed again to determine the embolization effect.

Example 2

Preparation of sodium alginate microspheres containing sodium cod liver oil

1. Preparation before the parcel:

1 glassware treatment:

2 Anti-angioma drug preparation of sodium cod liver oil solution:

Weigh 10 grams of commercially available sodium cod liver oil, placed in the above glassware, and dissolved in water to obtain a sodium cod liver oil drug solution;

3 Preparation of sodium alginate solution:

4 taking 12 grams of barium chloride to prepare a 12% by weight solution of barium chloride;

5 formulating liquid paraffin or vegetable oil as a preservation solution;

6 mixing the above sodium cod liver oil solution and sodium alginate solution to obtain a sodium alginate mixed solution containing sodium cod liver oil;

7 Aspirating the above mixture with a sterile syringe, passing through a high-voltage electrostatic microsphere generating device, setting various parameters, dropping into the above cerium chloride solution, and obtaining sodium alginate wet microspheres containing sodium cod liver oil. The particle size of the microspheres can be made into wet spheres or dry spheres of different size ranges as needed. For example, 20 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, 700 to 900 μm, and 900 to 1200 μm.

It is reduced to a wet bulb by soaking in physiological saline before use.

For patients with hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other hemangioma, interventional or interventional ultrasound, transfemoral (maxillofacial) The carotid artery was introduced into the catheter, inserted into the blood supply artery of the target organ, and angiography was performed. After the location, size, number and blood supply of the hemangioma were confirmed, the diameter of the embolization microsphere was determined according to the angiography. Use microcatheters as much as possible for superselective embolization, and use aseptically. Sodium alginate microspheres (wet bulbs) containing sodium cod liver oil, use a syringe to remove the preservation solution in the bottle, rinse the microspheres three times with an equal amount of physiological saline, or pour the preservation solution and the microspheres into the bottle. In a sterile bowl, rinse the microspheres with 50-60ml saline to discard the rinse solution, then add the appropriate amount or diluted contrast medium (so that the microspheres are fully suspended in the contrast agent), and see through the catheter under fluoroscopy. The lesion is injected slowly or slowly multiple times until the contrast agent flow rate is significantly slowed down, ie the embolization is completed. The angiography was performed again to determine the embolization effect.

Example 3

Preparation of sodium alginate microspheres containing urea

1. Preparation before the parcel:

1 glassware treatment:

2 Preparation of anti-angioma drug urea liquid:

Weigh 10 grams of commercially available urea, placed in the above glassware, and dissolved in water to obtain a urea drug solution;

3 Preparation of sodium alginate solution:

Weigh 600 grams of commercially available sodium alginate, place it in a glassware, and add physiological saline while stirring until all the sodium alginate is dissolved to obtain a sodium alginate solution;

4 take 6 grams of calcium chloride, prepare a 6 wt% calcium chloride solution;

5 formulating vegetable oil as a preservation solution;

6 mixing the above urea solution and sodium alginate solution to obtain a sodium alginate mixed solution containing urea;

7 Aspirating the above mixture with a sterile syringe, passing through a high-voltage electrostatic microsphere generating device, setting various parameters, and dropping into the calcium chloride solution to obtain a urea-containing sodium alginate wet microsphere. The particle size of the microspheres can be made into wet spheres or dry spheres of different size ranges as needed. For example, 20 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, 700 to 900 μm, and 900 to 1200 μm.

It is reduced to a wet bulb by soaking in physiological saline before use.

For patients with hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other hemangioma, interventional or interventional ultrasound, transfemoral (maxillofacial) The carotid artery was introduced into the catheter, inserted into the blood supply artery of the target organ, and angiography was performed. After the location, size, number and blood supply of the hemangioma were confirmed, the diameter of the embolization microsphere was determined according to the angiography. Use microcatheters as much as possible for superselective embolization, and use aseptically. Urea-containing sodium alginate microspheres (wet bulbs), use a syringe to remove the preservation solution in the bottle and rinse the microspheres three times with an equal amount of physiological saline, or pour the preservation solution and microspheres in the vial into the sterile In the bowl, rinse the microspheres with 50-60ml saline to discard the rinse solution, and then add the appropriate amount or diluted contrast agent (to fully suspend the microspheres in the contrast agent). The lesion is injected multiple times slowly until the contrast agent flow rate is significantly slowed down, ie the embolization is completed. The angiography was performed again to determine the embolization effect.

Example 4

Preparation of sodium alginate microspheres containing bleomycin

1. Preparation before the parcel:

1 glassware treatment:

2 Preparation of anti-angioma drug bleomycin solution:

Weigh 10 g of commercially available bleomycin, placed in the above glassware, and dissolved in water to obtain a bleomycin drug solution;

3 Preparation of sodium alginate solution:

4 take 10 grams of calcium chloride, prepare 10% by weight of calcium chloride solution;

5 preparing liquid paraffin as a preservation solution;

6 mixing the above bleomycin solution and sodium alginate solution to obtain a mixed solution of sodium alginate containing bleomycin;

7 Aspirating the above mixture solution with a sterile syringe, passing through a high-voltage electrostatic microsphere generating device, setting various parameters, and dropping into the above calcium chloride solution to obtain a wet microsphere of sodium alginate containing bleomycin. The particle size of the microspheres can be made into wet spheres or dry spheres of different size ranges as needed. For example, 20 to 50 μm, 50 to 100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, 700 to 900 μm, and 900 to 1200 μm.

It is reduced to a wet bulb by soaking in physiological saline before use.

For patients with hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other hemangioma, interventional or interventional ultrasound, transfemoral (maxillofacial) The carotid artery was introduced into the catheter, inserted into the blood supply artery of the target organ, and angiography was performed. After the location, size, number and blood supply of the hemangioma were confirmed, the diameter of the embolization microsphere was determined according to the angiography. Use microcatheters as much as possible for superselective embolization, and use aseptically. The lysine-containing alginate microspheres (wet bulbs) are pumped out of the bottle with a syringe and the microspheres are washed three times with an equal amount of physiological saline, or the preservation solution and the microspheres in the bottle are poured. Into the sterile bowl, rinse the microspheres with 50-60ml saline to discard the rinse solution, and then add the appropriate amount or diluted contrast agent (to fully suspend the microspheres in the contrast agent). The lesion is injected slowly or slowly multiple times until the contrast agent flow rate is significantly slowed down, ie the embolization is completed. The angiography was performed again to determine the embolization effect.

Industrial applicability

The raw material used in the invention has good mechanical strength, biocompatibility, biodegradability and stability, no organic solvent, no damage to the hematopoietic system and immune system function, and can be industrialized as a new embolic agent. It is used for embolization of hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other hemangioma. Used for various types of large thromboembolism to stop bleeding.

Claims

An alginate microsphere vascular embolization agent containing an anti-angioma drug, comprising: a carrier sodium alginate and an anti-hemangioma drug, the sodium alginate encapsulating the anti-angioma drug; the sodium alginate The weight ratio to the anti-angioma drug is 5:1 to 60:1; the anti-angioma drug is pingyangmycin, sodium cod liver oil, urea or bleomycin.
The anti-angioma drug-containing alginate microsphere vascular embolization agent according to claim 1, wherein the anti-angioma drug-containing alginate microsphere vascular embolization agent is micro-storage stored in a preservation solution. Ball or micro-beads.
The alginate drug-containing alginate microsphere vascular embolization agent according to claim 1, wherein the anti-hemangioma drug-containing alginate microsphere vascular embolization agent is powdery microparticles.
The anti-angioma drug-containing alginate microsphere vascular embolization agent according to claim 2, wherein the microspheres or microgels stored in the preservation solution have a particle size ranging from 20 to 50 μm, 50 ～100 μm, 100 to 200 μm, 200 to 300 μm, 300 to 500 μm, 500 to 700 μm, 700 to 900 μm, and 900 to 1200 μm.
The alginate microsphere-containing blood vessel embolizing agent containing an anti-angioma drug according to claim 3, wherein the powdery particles have a particle diameter ranging from 10 to 50 μm, 50 to 100 μm, 100 to 200 μm, and 200 to 200 Å. 300 μm, 300 to 500 μm, 500 to 700 μm, and 700 to 900 μm.
A method for preparing a sodium alginate microsphere vascular embolization agent containing an anti-angioma drug, the steps of which are as follows:

(1) weighing 1 part by weight of an anti-angioma drug, and dissolving it in water for injection to obtain an anti-angioma drug solution;

(2) 5 to 60 parts by weight of sodium alginate is weighed in proportion, and dissolved in water for injection or physiological saline to obtain a sodium alginate solution;

(3) weighing 2 parts by weight to 12 parts by weight of calcium chloride or cerium chloride, and dissolving in water for injection to obtain a solidifying liquid;

(4) mixing the anti-angioma drug solution obtained in the step (1) with the sodium alginate solution obtained in the step (2), and reacting with the solidified liquid obtained in the step (3) by the high-voltage electrostatic microsphere generating device to obtain an anti-angioma drug. Sodium alginate microsphere vascular embolization agent
The method for preparing an anti-angioma drug-containing alginate microsphere vascular embolization agent according to claim 6, wherein the high-voltage electrostatic microsphere generating device comprises: an electrostatic generating device, a mixer, a peristaltic accelerator, and a lifting device a table, a sterile glass container, a syringe, a special needle, connected to the positive and negative poles, the positive electrode connected to the needle of the injection device on the peristaltic accelerator, and the negative electrode connected to the stainless steel ring in the solidified liquid immersed in the sterile glass container The injection device contains a mixed solution of an anti-angioma drug and sodium alginate, and the spray is dropped into the solidified solution to form microspheres.
The method for preparing a sodium alginate microsphere vascular embolization agent containing an anti-angioma drug according to claim 6 or 7, wherein the obtained sodium alginate microsphere containing an anti-angioma drug is stored in liquid paraffin or vegetable oil. In the preservation solution.
The method for preparing a sodium alginate microsphere vascular embolization agent containing an anti-angioma drug according to claim 8, wherein the obtained sodium alginate microsphere containing an anti-angioma drug is freeze-dried in a freeze dryer. The wet microspheres were placed in an oven for 24 hours to obtain powdery granules.
The use of an anti-angioma drug-containing alginate microsphere vascular embolization agent according to any one of claims 1 to 5, characterized in that the algal acid containing an anti-angioma drug is monitored under the supervision of an imaging device Sodium microsphere vascular embolization agent is superselectively embolized into the blood vessels of the lesion by catheter (such as hepatic hemangioma, maxillofacial hemangioma, nasopharyngeal angiofibroma, surface hemangioma, uterine fibroids and other hemangioma) .