CN114366723B - Microsphere containing pirarubicin hydrochloride and preparation method and application thereof - Google Patents
Microsphere containing pirarubicin hydrochloride and preparation method and application thereof Download PDFInfo
- Publication number
- CN114366723B CN114366723B CN202111487701.9A CN202111487701A CN114366723B CN 114366723 B CN114366723 B CN 114366723B CN 202111487701 A CN202111487701 A CN 202111487701A CN 114366723 B CN114366723 B CN 114366723B
- Authority
- CN
- China
- Prior art keywords
- pirarubicin hydrochloride
- polyhydroxyalkanoate
- pirarubicin
- hydrochloride
- microsphere
- 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.)
- Active
Links
Images
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention belongs to the technical field of medical materials, and discloses a microsphere containing pirarubicin hydrochloride, a preparation method and application thereof. A microsphere containing pirarubicin hydrochloride comprises polyhydroxyalkanoate and pirarubicin hydrochloride loaded on polyhydroxyalkanoate. The invention adopts polyhydroxyalkanoate to load pirarubicin hydrochloride, and the prepared microsphere has uniform particle size and encapsulation rate of more than 99.90 percent by controlling the proportion of an oil phase to a water phase in the preparation, the selection of a surfactant and the concentration of the surfactant; the inhibition effect on tumors is better than that of the pirarubicin hydrochloride injection.
Description
Technical Field
The invention belongs to the technical field of medical materials, and particularly relates to a microsphere containing pirarubicin hydrochloride, a preparation method and application thereof.
Background
There are many methods for treating solid tumors and many related studies and reports. Among the various treatments, chemotherapy remains one of the common options. Although conventional chemotherapy has been used for a long time, the therapeutic effect on solid tumors is not certain, and the fundamental problem is that conventional chemotherapy cannot achieve an effective drug concentration at the tumor site and maintain a sufficient duration of action. Because the effect of chemotherapy depends not only on the sensitivity of the drug, the action time and the drug concentration of the drug at the tumor site are more important, but conventional chemotherapy cannot achieve the above objective, and inappropriate chemotherapy with low dose can not only induce the generation of drug resistance of tumor cells, but also stimulate the diffusion and metastasis of tumors.
Local application, particularly local slow release, of chemotherapeutic drugs has become the focus of current solid tumor chemotherapy research. The local chemotherapy can prolong the acting time of the medicine on the tumor part and improve the medicine concentration, thereby realizing the aim which cannot be realized by the conventional chemotherapy and reducing the possibility of inducing the drug resistance of tumor cells or stimulating the diffusion and metastasis of the tumor caused by the low-dose chemotherapy.
The prior biodegradable sustained and controlled release preparation uses solid polymer as sustained release carrier, such as polyglycolic acid, polylactic acid or copolymer thereof, etc. However, these slow release carriers have certain limitations, such as polylactic acid (PLA) has disadvantages of poor hydrophilicity, large molecular polarity, poor processability, high price, uncontrollable degradation period, and the like.
Pirarubicin hydrochloride is an antitumor drug for treating tumor of head and neck, breast cancer, gastric cancer, bladder cancer, renal pelvis, ureter tumor, ovarian cancer, uterine cancer, acute leukemia and malignant lymphoma. The sustained and controlled release preparation of the pirarubicin hydrochloride has more difficulties in preparation, and polylactic acid is adopted as a sustained release carrier, so that the prepared microsphere has nonuniform particle size and low encapsulation efficiency, and seriously affects the sustained release of the medicine and plays a good role.
Therefore, there is a need to provide a microsphere containing pirarubicin hydrochloride, which has uniform particle size, encapsulation efficiency and good slow release effect.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems in the prior art described above. Therefore, the microsphere containing the pirarubicin hydrochloride provided by the invention has the advantages of uniform particle size, encapsulation efficiency and good slow release effect.
The first aspect of the invention provides a microsphere containing pirarubicin hydrochloride.
Specifically, the microsphere containing the pirarubicin hydrochloride comprises polyhydroxyalkanoate and the pirarubicin hydrochloride loaded on the polyhydroxyalkanoate.
Preferably, the mass of the pirarubicin hydrochloride accounts for 1-8% of the mass of the polyhydroxyalkanoate; further preferably, the mass of the pirarubicin hydrochloride is 2% -5% of the mass of the polyhydroxyalkanoate.
Preferably, the polyhydroxyalkanoate is selected from at least one of hydroxybutyrate and hydroxyvalerate copolymer (PHBV), 3-hydroxybutyrate and 3-hydroxyhexanoate copolyester (PHBHHx), 3-hydroxybutyrate and 4-hydroxybutyrate copolyester (P34 HB), 3-hydroxybutyrate, 3-hydroxyhexanoate and 3-hydroxyvalerate copolymer (PHBVHx), polyhydroxyhexanoate (PHHx) or Polyhydroxyoctanoate (PHO).
The second aspect of the invention provides a preparation method of microspheres containing pirarubicin hydrochloride.
Specifically, the preparation method of the microsphere containing the pirarubicin hydrochloride comprises the following steps:
dissolving polyhydroxyalkanoate and pirarubicin hydrochloride in a solvent, and mixing to obtain an oil phase;
dissolving a surfactant in water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, and solidifying to obtain the microspheres containing the pirarubicin hydrochloride.
Preferably, the solvent is selected from at least one of N-methylpyrrolidone, methylene chloride, chloroform or acetonitrile.
Preferably, the dissolving process is to dissolve the polyhydroxyalkanoate and the pirarubicin hydrochloride in a solvent respectively to obtain polyhydroxyalkanoate solution and pirarubicin hydrochloride solution.
Preferably, in the polyhydroxyalkanoate solution, the mass concentration of the polyhydroxyalkanoate is 10-50mg/mL.
Preferably, in the pirarubicin hydrochloride solution, the mass concentration of the pirarubicin hydrochloride is 1-8mg/mL.
Preferably, the surfactant is selected from at least one of anionic surfactant, cationic surfactant or nonionic surfactant. Further preferably, the surfactant is at least one selected from stearic acid, sodium dodecyl benzene sulfonate, quaternary ammonium compound, lecithin, betaine, alkyl glucoside (APG), fatty acid glyceride, fatty acid sorbitan (span), polysorbate (tween), or polyvinyl alcohol; more preferably, the surfactant is polyvinyl alcohol.
Preferably, in the aqueous phase, the surfactant has a mass fraction of 1.8% to 8%; further preferably, in the aqueous phase, the surfactant is present in an amount of 1.8% to 5% by mass.
Preferably, the volume ratio of the oil phase to the water phase is 1: (3-15); further preferably, the volume ratio of the oil phase to the water phase is 1: (5-12).
The third aspect of the invention provides an application of microspheres containing pirarubicin hydrochloride.
In particular to application of the microsphere containing the pirarubicin hydrochloride in preparing anticancer drugs.
A medicament comprising the microsphere containing pirarubicin hydrochloride.
Compared with the prior art, the invention has the following beneficial effects:
the invention adopts polyhydroxyalkanoate to load pirarubicin hydrochloride, and the prepared microsphere has uniform particle size, the encapsulation rate is more than 99.90 percent, and the in-vitro release time is more than or equal to 30 days by controlling the proportion of an oil phase and a water phase in the preparation, the selection of a surfactant and the concentration of the surfactant (polyvinyl alcohol); the inhibition effect on tumors is better than that of the pirarubicin hydrochloride injection.
Drawings
FIG. 1 is a photomicrograph of the emulsion prepared in step (3) of example 1;
FIG. 2 is a mirror image of the emulsion prepared in step (3) of example 1 during curing;
FIG. 3 is a photomicrograph of the emulsion prepared in step (3) of example 1 after curing;
FIG. 4 is a graph showing the particle size distribution of the microspheres containing pirarubicin hydrochloride prepared in example 1;
FIG. 5 is a mirror image of the emulsion produced in step (3) of comparative example 1 during curing.
Detailed Description
In order to make the technical solutions of the present invention more apparent to those skilled in the art, the following examples will be presented. It should be noted that the following examples do not limit the scope of the invention.
The starting materials, reagents or apparatus used in the following examples are all available from conventional commercial sources or may be obtained by methods known in the art unless otherwise specified.
Example 1
A microsphere containing pirarubicin hydrochloride is prepared by loading polyhydroxyalkanoate.
The preparation method of the microsphere containing the pirarubicin hydrochloride comprises the following steps:
(1) Polyhydroxyalkanoate (3-hydroxybutyric acid and 4-hydroxybutyrate copolyester) is dissolved in methylene dichloride to prepare polyhydroxyalkanoate solution with the mass concentration of 30mg/mL, and pirarubicin hydrochloride is dissolved in methylene dichloride to prepare pirarubicin hydrochloride solution with the mass concentration of 3.4 mg/mL; then, 30mL of polyhydroxyalkanoate solution was mixed with 10mL of pirarubicin hydrochloride solution to obtain an oil phase.
(2) And dissolving the polyvinyl alcohol in water to obtain a water phase with the mass fraction of the polyvinyl alcohol being 2%.
(3) 30mL of the oil phase was poured into 280mL of the aqueous phase and stirred using an overhead stirrer with stirring blades of 6.5cm in width. 300r/min, and stirring for 42min. Making it a homogeneous emulsion. FIG. 1 is a photomicrograph of an emulsion, and as can be seen from FIG. 1, there are a plurality of microspheres in the emulsion, where the microspheres have not yet cured. Then 280mL of water is added into the emulsion prepared above, and the mixture is stirred by an overhead stirrer for 180r/min for 40h, and the organic solvent is volatilized in an open beaker for solidification, so as to prepare the microsphere containing the pirarubicin hydrochloride. Fig. 2 is a mirror image during emulsion curing, and fig. 3 is a mirror image after emulsion curing. Fig. 4 shows the particle size distribution diagram of the prepared microsphere containing pirarubicin hydrochloride, and as can be seen from fig. 4, the average particle size of the microsphere is 56um, the span value is 0.68, the particle size is uniform and controllable, and the stability of treatment can be ensured.
Example 2
A microsphere containing pirarubicin hydrochloride is prepared by loading polyhydroxyalkanoate.
The preparation method of the microsphere containing the pirarubicin hydrochloride comprises the following steps:
(1) Polyhydroxyalkanoate (3-hydroxybutyric acid and 4-hydroxybutyrate copolyester) is dissolved in methylene dichloride to prepare polyhydroxyalkanoate solution with the mass concentration of 30mg/mL, and pirarubicin hydrochloride is dissolved in methylene dichloride to prepare pirarubicin hydrochloride solution with the mass concentration of 3.4 mg/mL; then, 30mL of polyhydroxyalkanoate solution was mixed with 10mL of pirarubicin hydrochloride solution to obtain an oil phase.
(2) And dissolving the polyvinyl alcohol in water to obtain a water phase with the mass fraction of the polyvinyl alcohol being 3%.
(3) 30mL of the oil phase was poured into 280mL of the aqueous phase and stirred using an overhead stirrer with stirring blades of 6.5cm in width. 300r/min, and stirring for 42min. Making it a homogeneous emulsion. Then 280mL of water is added into the emulsion prepared above, and the mixture is stirred by an overhead stirrer for 180r/min for 40h, and the organic solvent is volatilized in an open beaker for solidification, so as to prepare the microsphere containing the pirarubicin hydrochloride.
Example 3
A microsphere containing pirarubicin hydrochloride is prepared by loading polyhydroxyalkanoate.
The preparation method of the microsphere containing the pirarubicin hydrochloride comprises the following steps:
(1) Polyhydroxyalkanoate (copolyester of 3-hydroxybutyric acid and 3-hydroxycaproic acid) is dissolved in dichloromethane to prepare polyhydroxyalkanoate solution with the mass concentration of 30mg/mL, and pirarubicin hydrochloride is dissolved in dichloromethane to prepare pirarubicin hydrochloride solution with the mass concentration of 3.4 mg/mL; then, 30mL of polyhydroxyalkanoate solution was mixed with 10mL of pirarubicin hydrochloride solution to obtain an oil phase.
(2) And dissolving the polyvinyl alcohol in water to obtain a water phase with the mass fraction of the polyvinyl alcohol being 2.5%.
(3) 30mL of the oil phase was poured into 280mL of the aqueous phase and stirred using an overhead stirrer with stirring blades of 6.5cm in width. 300r/min, and stirring for 42min. Making it a homogeneous emulsion. Then 280mL of water is added into the emulsion prepared above, and the mixture is stirred by an overhead stirrer for 180r/min for 40h, and the organic solvent is volatilized in an open beaker for solidification, so as to prepare the microsphere containing the pirarubicin hydrochloride.
Example 4
A microsphere containing pirarubicin hydrochloride is prepared by loading polyhydroxyalkanoate.
The preparation method of the microsphere containing the pirarubicin hydrochloride comprises the following steps:
(1) Polyhydroxyalkanoate (copolyester of 3-hydroxybutyric acid and 3-hydroxycaproic acid) is dissolved in dichloromethane to prepare polyhydroxyalkanoate solution with the mass concentration of 40mg/mL, and pirarubicin hydrochloride is dissolved in dichloromethane to prepare pirarubicin hydrochloride solution with the mass concentration of 5.0 mg/mL; then, 30mL of polyhydroxyalkanoate solution was mixed with 10mL of pirarubicin hydrochloride solution to obtain an oil phase.
(2) And dissolving the polyvinyl alcohol in water to obtain a water phase with the mass fraction of the polyvinyl alcohol being 2.5%.
(3) 30mL of the oil phase was poured into 280mL of the aqueous phase and stirred using an overhead stirrer with stirring blades of 6.5cm in width. 300r/min, and stirring for 42min. Making it a homogeneous emulsion. Then 280mL of water is added into the emulsion prepared above, and the mixture is stirred by an overhead stirrer for 180r/min for 40h, and the organic solvent is volatilized in an open beaker for solidification, so as to prepare the microsphere containing the pirarubicin hydrochloride.
Comparative example 1
Comparative example 1 was different from example 1 in that the mass fraction of polyvinyl alcohol in the aqueous phase was 1.5%, and the rest of the preparation method was the same as example 1.
Specifically, the preparation method of the composition containing the pirarubicin hydrochloride comprises the following steps:
(1) Polyhydroxyalkanoate (3-hydroxybutyric acid and 4-hydroxybutyrate copolyester) is dissolved in methylene dichloride to prepare polyhydroxyalkanoate solution with the mass concentration of 30mg/mL, and pirarubicin hydrochloride is dissolved in methylene dichloride to prepare pirarubicin hydrochloride solution with the mass concentration of 3.4 mg/mL; then, 30mL of polyhydroxyalkanoate solution was mixed with 10mL of pirarubicin hydrochloride solution to obtain an oil phase.
(2) And dissolving the polyvinyl alcohol in water to obtain a water phase with the mass fraction of the polyvinyl alcohol being 1.5%.
(3) 30mL of the oil phase was poured into 280mL of the aqueous phase and stirred using an overhead stirrer with stirring blades of 6.5cm in width. 300r/min, and stirring for 42min. Making it a homogeneous emulsion. Then 280mL of water was added to the emulsion prepared above, and the mixture was stirred with an overhead stirrer at 180r/min for 40 hours, and the organic solvent was evaporated in an open beaker to be solidified, thereby obtaining a composition containing pirarubicin hydrochloride. FIG. 5 is a light-mirror diagram of an emulsion in the curing process, and the emulsion is broken in the curing process, so that the prepared emulsion is unstable and cannot be cured into microspheres. As can be seen from comparative example 1, it is shown that the mass fraction of polyvinyl alcohol in the aqueous phase is important, and that the polyvinyl alcohol at a suitable concentration can stabilize the emulsion during the curing process without demulsification.
Comparative example 2
Comparative example 2 differs from example 1 in that 80mL of the aqueous phase was taken and the remainder of the preparation was the same as example 1. Specifically, the preparation method of the composition containing the pirarubicin hydrochloride comprises the following steps:
(1) Polyhydroxyalkanoate (3-hydroxybutyric acid and 4-hydroxybutyrate copolyester) is dissolved in methylene dichloride to prepare polyhydroxyalkanoate solution with the mass concentration of 30mg/mL, and pirarubicin hydrochloride is dissolved in methylene dichloride to prepare pirarubicin hydrochloride solution with the mass concentration of 3.4 mg/mL; then, 30mL of polyhydroxyalkanoate solution was mixed with 10mL of pirarubicin hydrochloride solution to obtain an oil phase.
(2) And dissolving the polyvinyl alcohol in water to obtain a water phase with the mass fraction of the polyvinyl alcohol being 2%.
(3) 30mL of the oil phase was poured into 80mL of the aqueous phase and stirred using an overhead stirrer with stirring blades of 6.5cm in width. 300r/min, and stirring for 42min. Making it a homogeneous emulsion. Then 280mL of water was added to the emulsion prepared above, and the mixture was stirred with an overhead stirrer at 180r/min for 40 hours, and the organic solvent was evaporated in an open beaker to be solidified, thereby obtaining a composition containing pirarubicin hydrochloride.
Product effect test
The pirarubicin hydrochloride-containing microspheres prepared in examples 1-4 and the pirarubicin hydrochloride-containing compositions prepared in comparative examples 1-2 were tested in the following manner: balling property, drug loading rate and encapsulation efficiency.
(1) Balling property
In the preparation, whether or not the ball can be formed is observed by a microscope. Through tests, the methods provided in examples 1-4 can prepare microspheres with good sphericity. Whereas comparative example 1 and comparative example 2 cannot prepare microspheres.
(2) Drug loading rate
The drug loading of the microspheres containing the pirarubicin hydrochloride is tested by adopting liquid chromatography.
Drug loading = drug content of microsphere/weight of microsphere.
The test parameters are as follows: the Epidertyil ODS 2C 18 column was 5 μm, 4.6X150 mm, methanol: water (50:50) was the mobile phase at a flow rate of 1.0ml/min and an ultraviolet detection wavelength of 237nm.
Test results: pirarubicin hydrochloride is linear in the range of 0.005-0.35umol/ml, r= 0.9992, and the lowest detection limit is 0.005umol/ml. The recovery rates of the low, medium and high concentrations (0.03, 0.1,0.3 umol/ml) were 101.33%, 102.43% and 102.04%, respectively, with RSD <4% and 1% during the day and day, respectively.
(3) Encapsulation efficiency
Encapsulation efficiency = drug content of microsphere/theoretical drug content of microsphere.
The test results of drug loading and encapsulation efficiency are shown in table 1.
TABLE 1
| Example 1 | Example 2 | Example 3 | Example 4 | Comparative example 1 | Comparative example 2 | |
| Drug loading rate | 1.5％ | 1.5％ | 1.48％ | 1.49％ | / | / |
| Encapsulation efficiency | 99.92％ | 99.90％ | 99.95％ | 99.90％ | 0 | 0 |
As can be seen from Table 1, the microspheres in examples 1-4 can be prepared with a drug loading of 1.48% or more and an encapsulation efficiency of 99.90% or more; however, the comparative example cannot prepare ideal microspheres, and thus, the pirarubicin hydrochloride cannot be well slowly released.
Meanwhile, preliminary in-vitro release time and in-vivo tumor inhibition tests are carried out on the microsphere containing the pirarubicin hydrochloride. The in vitro release time is tested by simulating physiological environment; in-vivo tumor inhibition tests are carried out by comparing the microsphere provided by the invention with pirarubicin hydrochloride injection. Through preliminary experiments, the in-vitro release time of the microsphere containing the pirarubicin hydrochloride provided by the invention is longer than 30 days, the tumor inhibition rate can reach more than 50%, and the effect is better than that of the pirarubicin hydrochloride injection.
Claims (7)
1. The microsphere containing the pirarubicin hydrochloride is characterized by comprising polyhydroxyalkanoate and the pirarubicin hydrochloride loaded on the polyhydroxyalkanoate;
the preparation method of the microsphere containing the pirarubicin hydrochloride comprises the following steps:
dissolving polyhydroxyalkanoate and pirarubicin hydrochloride in a solvent, and mixing to obtain an oil phase;
dissolving a surfactant in water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, and solidifying to obtain the microspheres containing the pirarubicin hydrochloride;
the polyhydroxyalkanoate is selected from at least one of a copolymer of hydroxybutyrate and hydroxyvalerate, a copolyester of 3-hydroxybutyrate and 3-hydroxyhexanoate, a copolyester of 3-hydroxybutyrate and 4-hydroxybutyrate, a copolymer of 3-hydroxybutyrate, 3-hydroxyhexanoate and 3-hydroxyvalerate, polyhydroxyhexanoate or polyhydroxyoctanoate;
the volume of the oil phase is 30mL, and the volume of the water phase is 280mL;
the surfactant is polyvinyl alcohol;
in the aqueous phase, the mass fraction of the surfactant is 2% -3%.
2. Microspheres according to claim 1, wherein the mass of the pirarubicin hydrochloride is 1-8% of the mass of the polyhydroxyalkanoate.
3. A method for preparing microspheres containing pirarubicin hydrochloride according to any one of claims 1-2, comprising the steps of:
dissolving polyhydroxyalkanoate and pirarubicin hydrochloride in a solvent, and mixing to obtain an oil phase;
dissolving a surfactant in water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, and solidifying to obtain the microspheres containing the pirarubicin hydrochloride.
4. The method according to claim 3, wherein the dissolution process is to dissolve polyhydroxyalkanoate and pirarubicin hydrochloride in a solvent respectively to obtain polyhydroxyalkanoate solution and pirarubicin hydrochloride solution.
5. The method according to claim 4, wherein the polyhydroxyalkanoate has a mass concentration of 10-50mg/mL; the mass concentration of the pirarubicin hydrochloride is 1-8mg/mL.
6. Use of the microspheres containing pirarubicin hydrochloride according to any one of claims 1-2 for the preparation of anticancer drugs.
7. A medicament comprising the pirarubicin hydrochloride-containing microsphere according to any one of claims 1-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111487701.9A CN114366723B (en) | 2021-12-06 | 2021-12-06 | Microsphere containing pirarubicin hydrochloride and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111487701.9A CN114366723B (en) | 2021-12-06 | 2021-12-06 | Microsphere containing pirarubicin hydrochloride and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114366723A CN114366723A (en) | 2022-04-19 |
| CN114366723B true CN114366723B (en) | 2023-07-07 |
Family
ID=81140106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111487701.9A Active CN114366723B (en) | 2021-12-06 | 2021-12-06 | Microsphere containing pirarubicin hydrochloride and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114366723B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101708175A (en) * | 2009-12-24 | 2010-05-19 | 辽宁大学 | Sustained release microsphere medicinal preparation using PHBHHx as carrier and method for preparing same |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ224549A (en) * | 1987-05-29 | 1990-04-26 | Ici Australia Operations | Controlled release polymer microspheres containing at least one active agent |
| JP2008528204A (en) * | 2005-01-28 | 2008-07-31 | テファ， インコーポレイテッド | Embolization using poly-4-hydroxybutyrate particles |
| US20150224221A1 (en) * | 2012-08-31 | 2015-08-13 | Chung-Ang University Industry-Academic Cooperation Foundation | Method for preparing microspheres for emboli, and method for preparing microspheres to which drug-containing carrier is bound |
| CN113616604B (en) * | 2021-10-12 | 2021-12-21 | 北京蓝晶微生物科技有限公司 | Injectable polyhydroxyalkanoate microspheres and preparation method thereof |
-
2021
- 2021-12-06 CN CN202111487701.9A patent/CN114366723B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101708175A (en) * | 2009-12-24 | 2010-05-19 | 辽宁大学 | Sustained release microsphere medicinal preparation using PHBHHx as carrier and method for preparing same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114366723A (en) | 2022-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101678113B (en) | Low-molecule drug-containing nanoparticle having sustained release negatively charged group | |
| Ruan et al. | Effects of material hydrophobicity on physical properties of polymeric microspheres formed by double emulsion process | |
| US5571525A (en) | Erosion rate modifier for use in bioerodible drug delivery devices and method of use | |
| Lu et al. | Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines | |
| EP1985309B1 (en) | Nanoparticles containing water-soluble non-peptide low-molecular weight drug | |
| Gryparis et al. | Effect of conditions of preparation on the size and encapsulation properties of PLGA-mPEG nanoparticles of cisplatin | |
| CA2805430A1 (en) | Method for preparing microspheres and microspheres produced thereby | |
| Parthipan et al. | One-step fabrication of bicompartmental microparticles as a dual drug delivery system for Parkinson’s disease management | |
| CN101108168B (en) | Method of manufacturing fulvestrant sustained-release microspheres | |
| Cheng et al. | Nucleobase‐Functionalized Supramolecular Micelles with Tunable Physical Properties for Efficient Controlled Drug Release | |
| WO2019108029A1 (en) | Sustained-release injection preparation containing donepezil and preparation method therefor | |
| Zhu et al. | Preparation and in vitro release behaviour of 5-fluorouracil-loaded microspheres based on poly (L-lactide) and its carbonate copolymers | |
| Shikanov et al. | Poly (sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel—effect of additives | |
| CN114366723B (en) | Microsphere containing pirarubicin hydrochloride and preparation method and application thereof | |
| Urbán-Morlán et al. | Preparation of ethyl cellulose nanoparticles by Solvent-Displacement using the conventional method and a recirculation system | |
| Yushu et al. | The effect of process variables on the morphology and release characteristics of protein‐loaded PLGA particles | |
| de Souza et al. | Has PEG-PLGA advantages for the delivery of hydrophobic drugs? Risperidone as an example | |
| Lee et al. | Hardly water-soluble drug-loaded gelatin nanoparticles sustaining a slow release: preparation by novel single-step O/W/O emulsion accompanying solvent diffusion | |
| RU2681933C1 (en) | Method for obtaining polymeric anti-tumor particles in flow microreactor and lyophilisate based on them | |
| CN101612111A (en) | Sustained-release micro-spheres of nomegestrol acetate or its analog and its production and use | |
| CN1923171B (en) | Compound recipe anti-cancer drugs slow release agent comprising anticancer antibiotics and synergist thereof | |
| CN101380303A (en) | Anti-cancer medicine sustained-released injection loaded with platinum compound and synergist thereof | |
| Sehra et al. | Formulation and evaluation of sustained release microspheres of poly-lactide-co-glycolide containing tamoxifen citrate | |
| Kaptan et al. | Enzymatic PCL-grafting to NH2-end grouped silica and development of microspheres for pH-stimulated release of a hydrophobic model drug | |
| Elsayed et al. | Formulation, characterization and in-vitro evaluation of solid lipid nanoparticles for the delivery of a new anticancer agent, 1H-pyrazolo [3, 4-d] pyrimidine derivative |
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 |