CN102166196A - Local injection-type carboplatin microspheres and method for preparing same - Google Patents
Local injection-type carboplatin microspheres and method for preparing same Download PDFInfo
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- CN102166196A CN102166196A CN2011100860095A CN201110086009A CN102166196A CN 102166196 A CN102166196 A CN 102166196A CN 2011100860095 A CN2011100860095 A CN 2011100860095A CN 201110086009 A CN201110086009 A CN 201110086009A CN 102166196 A CN102166196 A CN 102166196A
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Abstract
The invention relates to carboplatin microspheres for local injection and a method or preparing the same. The preparation is the microspheres which are formed by carboplatin and biologically degradable materials and can slowly release carboplatin in human tissues. The preparation method comprises the following steps of: suspending carboplatin crystals in a proper amount of organic solution of biologically degradable materials to prepare suspension; at room temperature, dropwise adding the suspension into mineral oil solution while stirring for emulsion; volatilizing, cleaning and solidifying the emulsified solution, and filtering to obtain carboplatin microspheres; washing the filtered carboplatin microspheres by using ultra pure water and performing decompression drying; and screening the microspheres with the grain size suitable for injection by using a medicinal screen, and collecting the microspheres for later use. The preparation can be used for tumor injection, locally form a sustained high-drug concentration zone in tumors and act on tumor cells for a long time, but cause a lower side effect on other normal cells.
Description
Technical field
The invention belongs to a kind of new medicinal preparation, particularly a kind of carboplatin microsphere that is used for local injection and preparation method thereof.
Background technology
Many neoplastic disease for example cancer are the common diseases of serious threat human life health, and chemotherapy is one of most common therapeutic method.Yet, usually cancer therapy drug does not have special selectivity to tumor cell and normal somatic cell, and the drug level that is gathered in tumor by local after the method that the is administered systemically treatment commonly used is low, and toxic and side effects is obvious, limited the heavy dose of chemotherapeutics and used, made clinical efficacy poor.
The chemotherapy of ultrasonic guidance tumor by local is under the real-time ultrasound guiding, directly injects chemotherapeutics to tumor by local.This method can make chemotherapeutics act on tumor region, directly causes neoplasm necrosis, and its influence factor is few, and effect is stable, and is little to normal tissue injury, complication is few.There is the scholar that anticarcinogen such as anhydrous alcohol, cisplatin ethanol liquid are injected directly in the tumor bodies such as hepatocarcinoma, cancer of pancreas, kills the cancerous protuberance cell, reduce systemic toxic side effect by chemistry or physical effect, and damage little.Yet its weak point is that cancer therapy drug soaks into and internal metabolism with interstice, is difficult to form persistent medicine high density area in the target area, does not reach the effect of interstitial laser photocoagulation complete inactivation, and the potentiality of medicine chemotherapy can not be given full play to.This does not only reach doctor and the desired chemotherapy effect of patient, and long-term repeatedly chemotherapy is returned the patient and brought a lot of miseries.
Summary of the invention
The technical problem to be solved in the present invention provides and a kind ofly can be applied to local injection and can continue form the medicine high concentration region at tumor by local, and long duration of action is in tumor cell and to lower pharmaceutical preparation of other Normocellular side effect and preparation method thereof.
In order to solve the problems of the technologies described above, the invention provides a kind of local injection type carboplatin microsphere, it is characterized in that, be the microball preparation that can in tissue, slowly discharge carboplatin that forms by carboplatin and Biodegradable material.
Further, described Biodegradable material is poly-D, L lactic acid, L lactic acid and D, any in the copolymer of the copolymer of the block copolymer of L lactic acid, lactic acid and glycolic, lactic acid and P PDO and the block copolymer of lactic acid and ethylene glycol.
With various Biodegradable materials is the preparing carriers carried medicine sustained-release microsphere, can make the chemotherapeutics targeting, slowly discharge, and improves the tumor by local drug level, strengthens the chemotherapy result, alleviates the whole body toxic and side effects simultaneously.
Further, described Biodegradable material is lactic acid and co-glycolic acid (PLGA).Lactic acid and co-glycolic acid (PLGA) because of have following characteristics become application at most, one of slow-released carrier the most widely: 1. can effectively improve the biocompatibility with hydroaropic substance such as protein, prolong the half-life in vivo; 2. favorable biological degradability mainly is degraded into acidic metabolite by the ester bond decomposition, finally gets rid of in external, nontoxic, the no body with water and carbon dioxide and assembles; 3. polymerization is simple, controllability is strong, slow release effect is better, inexpensive.
The present invention also provides a kind of method for preparing the carboplatin microsphere, and its step is as follows:
(1) the carboplatin crystal is suspended in the organic solution of an amount of Biodegradable material, makes suspension;
(2) under the room temperature, suspension is splashed in the mineral oil solution of the emulsifying agent in the stirring and carry out emulsifying;
(3) solution after the emulsifying is volatilized, cleans, solidifies, filter out the carboplatin microsphere then;
(4) the carboplatin microsphere that filters out is carried out drying under reduced pressure after the ultra-pure water washing;
(5) microsphere of the required particle diameter of injection is sifted out in medication, collects standby.
Technical scheme provided by the present invention has following advantage compared to existing technology: when the treatment entity tumor, utilize the slow releasing function of carboplatin microsphere, chemotherapeutics is discharged lastingly, in the local persistence high concentration compact district that forms of tumor body, direct kill cancer cell, and the toxic and side effects of normal histoorgan is dropped to bottom line, to obtain better chemotherapy effect.Because the properties of Aqueous Solution instability of carboplatin, therefore in the preparation process of carboplatin microsphere, what adopt during emulsifying is the mineral oil solution of emulsifying agent, so not only can make the carboplatin microsphere stable in properties of making, can long preservation, and can increase the drug loading of microsphere.
In addition, the drug loading of carboplatin microsphere also is subjected to the influence of the rate of charge of the organic solution concentration of Biodegradable material and carboplatin and Biodegradable material.For economical with materials and improve the drug loading of prepared microsphere, further, the concentration of the organic solution of described Biodegradable material is generally 6%～10%.The adjustment of concentration under the prerequisite that does not influence rate of charge, can realize by the content of adjusting solvent (as water).
Further again, the organic solution rate of charge of carboplatin and Biodegradable material was generally 1: 4～1: 8.
After the carboplatin microsphere of making carries out drying under reduced pressure, can be required according to when treatment injection, the microsphere that medication filters out required particle diameter directly injects to tumor by local.The carboplatin drug effect directly causes neoplasm necrosis in tumor region, and its influence factor is few, and effect is stable, and is little to normal tissue injury, complication is few.
The specific embodiment
A kind of local injection type carboplatin microsphere, said preparation are the microspheres that can slowly discharge carboplatin in tissue that is formed by carboplatin crystal and Biodegradable material lactic acid and co-glycolic acid (PLGA).The preparation method of above-mentioned carboplatin microsphere, its step is as follows:
(1) concentration that 62.5mg carboplatin crystal is suspended in 5ml is in 8% the lactic acid and co-glycolic acid (PLGA) acetone soln;
(2) under the room temperature, suspension splashed in the span-80 mineral oil solution in the stirring carry out emulsifying;
(3) solution after the emulsifying is volatilized, cleans, solidifies, filter out the carboplatin microsphere then;
(4) the carboplatin microsphere that filters out is carried out drying under reduced pressure after the ultra-pure water washing;
(5) microsphere of the required particle diameter of injection is sifted out in medication, collects standby.
The drug loading of carboplatin microsphere mainly is subjected to the influence of the rate of charge of the organic solution concentration of Biodegradable material and carboplatin and Biodegradable material, and therefore, strict these two conditions of control are crucial.Can make the carboplatin microsphere obtain higher drug loading again in order to save material, can further limit, the concentration of the organic solution of described Biodegradable material is generally 6%～10%, and lactic acid and co-glycolic acid (PLGA) acetone soln concentration is 8% as used herein.Further again, the organic solution rate of charge of carboplatin and Biodegradable material was generally 1: 4～1: 8, and the organic solution rate of charge of carboplatin and lactic acid and co-glycolic acid (PLGA) is 1: 7 in this process.
The carboplatin microsphere for preparing under this kind condition, its drug loading can reach 11.6%.The carboplatin microsphere that diameter is 100～200 μ m is sifted out in medication, and such microsphere can pass through medium size PCT pin, can be conveniently used in ultrasonic accurate location navigation local injection process.Under the real-time ultrasound guiding, in tumor, directly inject chemotherapeutics and make chemotherapeutics act on tumor region, directly cause neoplasm necrosis, its influence factor is few, and effect is stable.Carboplatin slowly discharges in human body, reduced the side effect of medicine, reached 15 days its release time (general pharmaceutical release time 3～5 days), in tumor, formed the high concentration region of long period other nonneoplastic tissues of patient, increase the utilization ratio of drug of carboplatin, reduced the chemotherapy number of times.
For a person skilled in the art, under the prerequisite that does not break away from the present invention program, can also make some improvement, can be equal to as used Biodegradable material among the above-mentioned embodiment and to replace with poly-D, L lactic acid, L lactic acid and D, any in the copolymer of the copolymer of the block copolymer of L lactic acid, lactic acid and glycolic, lactic acid and P PDO and the block copolymer of lactic acid and ethylene glycol.
And, can further limit, the concentration of the organic solution of described Biodegradable material is 6%～10%, as 7%, 8%, 10%.
Further again, the organic solution rate of charge of carboplatin and Biodegradable material was 1: 4～1: 8, such as 1: 5,1: 7,1: 8.
The carboplatin microsphere drug loading of preparing under this kind condition also can reach about 10%.Therefore, these also should be considered as protection scope of the present invention, all do not influence effect of the invention process and inventive and practicality.
Claims (6)
1. a local injection type carboplatin microsphere is characterized in that: be the microball preparation that can slowly discharge carboplatin in tissue that is formed by carboplatin and Biodegradable material.
2. local injection type carboplatin microsphere as claimed in claim 1, it is characterized in that, described Biodegradable material is poly-D, L lactic acid, L lactic acid and D, any in the copolymer of the copolymer of the block copolymer of L lactic acid, lactic acid and glycolic, lactic acid and P PDO and the block copolymer of lactic acid and ethylene glycol.
3. local injection type carboplatin microsphere as claimed in claim 1 is characterized in that, described Biodegradable material is lactic acid and co-glycolic acid (PLGA).
4. as the preparation method of each described local injection type carboplatin microsphere in the claim 1 to 3, it is characterized in that this preparation method may further comprise the steps:
(1) the carboplatin crystal is suspended in the organic solution of an amount of Biodegradable material, makes suspension;
(2) under the room temperature, suspension is splashed in the mineral oil solution of the emulsifying agent in the stirring and carry out emulsifying;
(3) solution after the emulsifying is volatilized, cleans, solidifies, filter out the carboplatin microsphere then;
(4) the carboplatin microsphere that filters out is carried out drying under reduced pressure after the ultra-pure water washing;
(5) microsphere of the required particle diameter of injection is sifted out in medication, collects standby.
5. the preparation method of local injection type carboplatin microsphere as claimed in claim 4 is characterized in that the concentration of the organic solution of described Biodegradable material is 6%～10%.
6. the preparation method of local injection type carboplatin microsphere as claimed in claim 4 is characterized in that the organic solution rate of charge of described carboplatin and Biodegradable material is 1: 4～1: 8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2011100860095A CN102166196A (en) | 2011-04-07 | 2011-04-07 | Local injection-type carboplatin microspheres and method for preparing same |
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| CN2011100860095A CN102166196A (en) | 2011-04-07 | 2011-04-07 | Local injection-type carboplatin microspheres and method for preparing same |
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| CN102166196A true CN102166196A (en) | 2011-08-31 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112870533A (en) * | 2020-12-21 | 2021-06-01 | 科塞尔医疗科技（苏州）有限公司 | Medicine carrying microsphere preparation device |
-
2011
- 2011-04-07 CN CN2011100860095A patent/CN102166196A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 皋月娟等: "生物降解型卡铂微球体外释放过程及其机理研究", 《临床超声医学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112870533A (en) * | 2020-12-21 | 2021-06-01 | 科塞尔医疗科技（苏州）有限公司 | Medicine carrying microsphere preparation device |
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Application publication date: 20110831 |