CN116270479A - Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition - Google Patents

Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition Download PDF

Info

Publication number
CN116270479A
CN116270479A CN202310286091.9A CN202310286091A CN116270479A CN 116270479 A CN116270479 A CN 116270479A CN 202310286091 A CN202310286091 A CN 202310286091A CN 116270479 A CN116270479 A CN 116270479A
Authority
CN
China
Prior art keywords
fluorouracil
drug
pure
particles
scar
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202310286091.9A
Other languages
Chinese (zh)
Other versions
CN116270479B (en
Inventor
刘刚
何鹏
程红伟
张建中
楚成超
张阳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Xiamen University
Original Assignee
Xiamen University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Xiamen University filed Critical Xiamen University
Priority to CN202310286091.9A priority Critical patent/CN116270479B/en
Publication of CN116270479A publication Critical patent/CN116270479A/en
Application granted granted Critical
Publication of CN116270479B publication Critical patent/CN116270479B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides a preparation method of fluorouracil pure drug nano particles, which comprises the following steps: s1, dissolving fluorouracil pure medicine in a solvent to obtain a medicine solution; s2, introducing CO into the reactor 2 Leading the drug solution obtained in the step S1 into a reactor for reaction for 1.5-2h at a rate of 1.5-3.0mL/min after the temperature is stabilized at 60-70 ℃ and the pressure is stabilized at 22-28MPa until the pressure is 20-28 MPa; s3, spraying the mixed solution obtained in the step S2 into an expansion chamber at a rate of 0.5-2.0mL/min to form microdroplets, and then removing the solvent in the microdroplets to obtain fluorouracil pure drug nano particles.

Description

Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition
Technical Field
The invention relates to novel fluorouracil pure drug nano particles and application thereof in scar inhibition, and belongs to the technical field of medicines.
Background
Pathological scar (hypertrophic scar and keloid) formation is the result of abnormal healing of skin wound surface, mainly due to excessive and abnormal proliferation of scar cells, local vascular proliferation plays a key role in the scar growth and recurrence process, which also causes excessive proliferation and redness of scar appearance, can cause pain, itching and other discomfort of patients, and seriously can cause joint dysfunction, deformity, psychological damage and the like. The exact mechanism of scarring is currently ambiguous, and there are many different therapeutic strategies for anti-scarring treatment, but no standard, ideal, stable therapeutic regimen exists. The in-situ local drug injection treatment of the scar is still a first-line mainstream treatment mode at present because of convenient and simple operation, wherein 5-fluorouracil (5-FU) is the main first-line drug which is selectable in the current local drug injection treatment of the hypertrophic scar. At present, 5-fluorouracil needs a large dosage (50 mg/ml) and is frequently injected to achieve better curative effect. However, side effects of large-dose and frequent injection are remarkable, such as scar local tissue necrosis, ulcer, pain, burning sensation, skin atrophy, pigmentation, exfoliation, a certain recurrence rate, and the like. If a low concentration of 5-fluorouracil is used, side effects resulting from the use of high concentrations of fluorouracil do not occur. However, the low concentration of 5-fluorouracil does not cause obvious atrophy of the scar, and the scar atrophy can be inhibited by combining with other medicines (hormone such as triamcinolone acetonide) or treatment methods (laser treatment and the like), but the corresponding treatment difficulty exists by combining with other treatment methods, the triamcinolone acetonide has hormone-related side effects, the laser can further increase pain and discomfort, and expensive instruments are excessively relied on.
The pathological scar tissue is a fibrotic compact structure, keloids have proved to have tumor-like characteristics, which suggests that research results of reference tumor in the research and treatment of scar are of great significance, and nano-sized drugs have the following advantages in tumor treatment: the nanometer size medicine is favorable for realizing endocytosis and tumor enrichment, and the effective dosage of the medicine at the tumor part is improved; improves the bioavailability of the medicine and reduces the dosage of the medicine. In theory, the fluorouracil pure drug nano-particles have the advantages in scar treatment, however, the existing 5-fluorouracil nano-drugs are often carried, and the carried nano-dosage forms have potential safety hazards due to the doping of other substances, and meanwhile, the drug loading capacity and the drug delivery efficiency are the problems to be solved.
Therefore, there is an urgent need to develop a novel nanoparticle of 5-fluorouracil that can overcome the above-mentioned drawbacks.
Disclosure of Invention
The invention provides a novel fluorouracil pure drug nano particle and application thereof in scar inhibition, which can effectively solve the problems
The invention is realized in the following way:
the preparation method of the fluorouracil pure drug nano-particles comprises the following steps:
s1, dissolving fluorouracil pure medicine in a solvent to obtain a medicine solution;
s2, introducing CO into the reactor 2 Leading the drug solution obtained in the step S1 into a reactor for reaction for 1.5-2h at a rate of 1.5-3.0mL/min after the temperature is stabilized at 60-70 ℃ and the pressure is stabilized at 22-28MPa until the pressure is 20-28 MPa;
s3, spraying the mixed solution in the reactor into an expansion chamber at the rate of 0.5-2.0mL/min to form microdrops, and then removing the solvent in the microdrops to obtain fluorouracil pure drug nano particles.
As a further improvement, the solvent is methanol or ethanol.
As a further improvement, the drug concentration of the drug solution is 10-15mg/mL.
As a further improvement, the temperature in step S2 is stabilized at 65 ℃.
As a further improvement, the pressure in step S2 is stabilized at 25MPa.
As a further improvement, the rate in step S2 is 2mL/min.
As a further improvement, the rate in step S3 is 1mL/min.
Fluorouracil pure drug nano-particles prepared by the method.
Application of the fluorouracil pure drug nano-particles in preparing drugs for inhibiting scars.
The beneficial effects of the invention are as follows:
the fluorouracil pure drug nano-particles are prepared by a supercritical method, no carrier exists, no other cosolvent, emulsion or other reagents possibly causing in vivo toxicity are introduced during the preparation process of the fluorouracil pure drug nano-particles, and the drug loading rate reaches 100%.
According to the fluorouracil pure drug nano-particles, the nano-drug with a compact structure is prepared by controlling the concentration, pressure and reaction temperature of the drug in the preparation process, so that a guarantee is provided for the sustained release of the drug in a disease area.
The invention can prolong the detention time of fluorouracil in scar tissue and improve the effective dose of medicine at the scar tissue. Compared with non-nano fluorouracil pure medicine, the medicine has the effect of inhibiting hypertrophic scar at a lower concentration (5 mg/ml), and can reduce the side effect of the conventional high-concentration (50 mg/ml) medicine.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some examples of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is an SEM image of drug particles of example 1 and comparative examples 1-2 of the invention.
FIG. 2 is a graph showing comparison of cell viability of HKF cells provided in example 3 of the present invention at different concentrations of the drug of example 1 and the drug of comparative example 1.
FIG. 3 is a graph showing comparison of cell activity rates of HUVEC cells provided in example 3 of the present invention at different concentrations of the drug of example 1 and the drug of comparative example 1.
FIG. 4 is a graph showing comparison of the retention rate of fluorouracil on day 2 in both comparative example 1 and example 1 provided in example 4 of the present invention.
FIG. 5 is a graph showing comparison of the retention rate of fluorouracil on day 4 in both comparative example 1 and example 1 provided in example 4 of the present invention.
Fig. 6 is a graph showing anti-rabbit ear scar efficacy of the drugs of comparative example 1 and example 1 provided in example 5 of the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, based on the embodiments of the invention, which are apparent to those of ordinary skill in the art without inventive faculty, are intended to be within the scope of the invention. Thus, the following detailed description of the embodiments of the invention, as presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, based on the embodiments of the invention, which are apparent to those of ordinary skill in the art without inventive faculty, are intended to be within the scope of the invention.
The embodiment of the invention provides a preparation method of fluorouracil pure drug nano particles, which comprises the following steps:
s1, dissolving fluorouracil pure medicine in a solvent to obtain a medicine solution;
s2, introducing CO into the reactor 2 Leading the drug solution obtained in the step S1 into a reactor for reaction for 1.5-2h at a rate of 1.5-3.0mL/min after the temperature is stabilized at 60-70 ℃ and the pressure is stabilized at 22-28MPa until the pressure is 20-28 MPa;
s3, spraying the mixed solution in the reactor into an expansion chamber at the rate of 0.5-2.0mL/min to form microdrops, and then removing the solvent in the microdrops to obtain fluorouracil pure drug nano particles.
As a further improvement, the solvent is methanol or ethanol, and can be used for efficiently dissolving fluorouracil.
As a further improvement, the drug concentration of the drug solution is 10-15mg/mL, which is favorable for the supercritical CO of the drug 2 The supersaturation state is reached after the treatment.
As a further improvement, the temperature in step S2 is stabilized at 65 ℃, and the mixed solution and supercritical CO are lifted 2 Degree of mixing.
As a further improvement, the pressure in the step S2 is stabilized at 25MPa, and the mixed solution and the supercritical CO are lifted 2 Degree of mixing.
As a further improvement, the rate in step S2 is 2mL/min.
As a further improvement, the speed in the step S3 is 1mL/min, so that the droplet formation uniformity is improved, and the nano particles with regular morphology and uniform size are formed.
Fluorouracil pure drug nano-particles prepared by the method.
Application of the fluorouracil pure drug nano-particles in preparing drugs for inhibiting scars.
Example 1 preparation of Carrier-free fluorouracil drug-pure nanoparticles
(1) Dissolving 500mg fluorouracil in 50mL methanol to obtain a drug solution with a concentration of 10 mg/mL;
(2) In the form of CO 2 Pressurizing a reaction kettle of the supercritical preparation device to 22MPa for an air source, and pumping the medicine solution obtained in the step (1) into the reaction kettle at a rate of 2.0mL/min for reaction for 1.0h after the temperature and the pressure are stabilized at 65 ℃ and 25MPa so as to enable fluorouracil to react in supercritical CO 2 Mixing uniformly in the state. After the reaction is finished, the mixed solution in the reactor is sprayed into an expansion chamber at the speed of 0.5-2.0mL/min to form microdroplets, and then the solvent in the microdroplets is removed to obtain fluorouracil pure drug particles.
Finally, the fluorouracil pure drug particles are dispersed into the water solution with the concentration of 10mg/ml.
Comparative example 1
(1) Dissolving 500mg fluorouracil in 50mL methanol to obtain a drug solution with a concentration of 10 mg/mL;
(2) In the form of CO 2 Will be made supercritical for air sourcePressurizing a reaction kettle of the device to 12MPa, pumping the drug solution obtained in the step (1) into the reaction kettle at a rate of 2.0mL/min for reaction for 1.0h after the temperature and the pressure are stabilized at 40 ℃ and 12MPa, so that fluorouracil reacts in supercritical CO 2 Mixing uniformly in the state. After the reaction is finished, slowly opening the pressure release valve to release CO 2 At the same time with CO 2 And decompressing to remove the solvent, and collecting to obtain the drug particles.
Comparative example 2
The difference from example 1 is that the drug concentration of the drug solution is 2mg/mL, and the procedure of example 1 is otherwise followed.
EXAMPLE 2 electron microscopic scanning observations of drugs
The drug particles obtained in example 1 and comparative examples 1 to 2 were observed by electron microscopic scanning, and the results are shown in FIG. 1.
As shown in fig. 1, the size of the drug-eluting particles in example 1 is nano-sized, which is a drug-eluting nanoparticle, which is very advantageous for achieving endocytosis and enrichment in scar tissue. The nano particles can be stably dispersed in the aqueous solution, and a guarantee is provided for local drug injection; the particles in comparative example 1 were irregularly shaped, non-uniform in size, and were micron-sized particles; in comparative example 2, the particles were agglomerates, no obvious nanostructure was found, and the preparation solution was flocculent agglomerates, which could not be examined for medication. The comparison of the results of example 1 and comparative example 1 in fig. 1 illustrates that the preparation process of the pure drug nanoparticles prepared in this example, such as the pressure and temperature of the reaction kettle, whether the reaction kettle is sprayed into the expansion chamber to form droplets, is very critical, and it is difficult to form qualified nanostructures if certain conditions are not satisfied. The comparison of the results of example 1 and comparative example 2 in fig. 1 shows that the drug concentration of the pure drug nanoparticles prepared in this example is also very critical, and the nanostructure can be formed only under the proper concentration condition, otherwise, the nanostructure is difficult to form.
EXAMPLE 3 comparison of the cell Activity of drugs against different cells
Human keloid fibroblasts HKF or human umbilical vein endothelial cells HUVECs were inoculated into 96-well plates, placed in a cell incubator for 24 hours, and washed twice with DPBS. After incubating the cells with fluorouracil drug particles of different concentrations (calculated as 5Fu concentration, prepared fluorouracil drug particles of example 1 and comparative example 1 were formulated as drug solutions of 12.5, 25, 50, 100, and 200. Mu.g/mL, respectively) for 24 Hours (HKF) or 48 Hours (HUVEC), each well was incubated with CCK-8 solution for 4 hours, absorbance (OD) values were read at a wavelength of 450nm in a microplate reader, and cell activity rates were calculated.
As shown in FIG. 2, the cell activity rate of human keloid fibroblasts HKF in the drug group of example 1 was lower than that in the drug group of comparative example 1, and fluorouracil drug-free nanoparticles had an effect of inhibiting the activity of human keloid fibroblasts HKF at a lower concentration (12.5. Mu.g/mL).
As shown in FIG. 3, the cell activity rate of the human umbilical vein endothelial cells HUVEC in the drug group of example 1 was lower than that of the drug group of comparative example 1, and the fluorouracil drug-free nanoparticles had the effect of inhibiting the activity of the human umbilical vein endothelial cells HUVEC at a lower concentration (12.5. Mu.g/mL).
The results in fig. 2 and 3 demonstrate that the drug of example 1 has much higher toxicity to scar cells than the drug of comparative example 1 at equal concentrations, which can increase the bioavailability of the drug and reduce the drug dose.
EXAMPLE 4 comparison of drug retention in scar tissue
And (3) establishing a rabbit ear ventral scar model by using an operation method, injecting fluorouracil pure drug nanoparticle solution and fluorouracil pure drug solution with the same concentration into the scar after the model is successfully prepared, taking scar tissue after 2 days and 4 days, shearing and crushing (1 mm), grinding for a plurality of times by using a freeze grinder to obtain minced meat, adding deionized water with the same integration, fully vibrating and uniformly mixing at a low temperature, extracting, centrifuging, and taking supernatant. The drug content was determined at 265nm by UV spectrophotometry, with scar model group as negative control. The concentration of drug was then calculated under the same conditions using a linear calibration curve (R2 > 0.99) of known 5-FU concentration.
As shown in fig. 4, fluorouracil in the example 1 drug group had a higher retention rate in scar tissue at 2 as compared to the comparative example 1 drug group. As shown in fig. 5, fluorouracil in the example 1 drug group also had a higher retention rate in scar tissue at 4 days as compared to the comparative example 1 drug group. Under the same drug concentration, the pure drug nano particles have longer action time in scar tissues, can reduce the metabolism of soft tissues on the drugs, enhance the enrichment of the scar tissues and improve the effective dose of the drugs at the scar tissue parts.
EXAMPLE 5 pharmaceutical use for anti-rabbit ear scar treatment
And (3) establishing a rabbit ear ventral scar model by using an operation method, and after the model is successfully prepared. Each scar tissue was injected with the same volume of the aqueous solution of fluorouracil particles of example 1, the aqueous solution of fluorouracil particles of comparative example 1, both of which were measured as fluorouracil at a drug concentration of 5mg/ml (1/10 of the conventional use concentration of 50 mg/ml), and no scar treated was used as a control group. The injections were continued 4 times at 1 week intervals. Scar efficacy was assessed one week after the 4 th injection before and after the injection.
As shown in fig. 6, scar hyperplasia was significantly inhibited and redness was not apparent in the group treated with the drug injection of example 1. The scars of the drug group and the fluorouracil pure aqueous solution group in comparative example 1 are obviously proliferated and red is obvious.
In conclusion, the carrier-free fluorouracil pure drug nano particles provided by the invention can simultaneously inhibit the activities of human keloid fibroblasts HKF and vascular endothelial cells HUVEC under the condition of low concentration (12.5 mug/mL), and the nano drugs can prolong the residence time of fluorouracil in scar tissues and improve the effective dose of the drugs in the scar tissues. Compared with non-nano fluorouracil pure medicine, the rabbit ear scar model has the effect of inhibiting hypertrophic scar at a lower concentration (5 mg/ml), and can reduce the side effect of using the conventional high-concentration (50 mg/ml) medicine.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, and various modifications and variations may be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (9)

1. The preparation method of the fluorouracil pure drug nano-particles is characterized by comprising the following steps:
s1, dissolving fluorouracil pure medicine in a solvent to obtain a medicine solution;
s2, introducing CO into the reactor 2 Leading the drug solution obtained in the step S1 into a reactor for reaction for 1.5-2h at a rate of 1.5-3.0mL/min after the temperature is stabilized at 60-70 ℃ and the pressure is stabilized at 22-28MPa until the pressure is 20-28 MPa;
s3, spraying the mixed solution in the reactor into an expansion chamber at the rate of 0.5-2.0mL/min to form microdrops, and then removing the solvent in the microdrops to obtain fluorouracil pure drug nano particles.
2. The method for preparing fluorouracil pure drug nanoparticles according to claim 1, wherein the solvent is methanol or ethanol.
3. The method for preparing fluorouracil pure drug nanoparticles according to claim 1, wherein the drug concentration of the drug solution is 10-15mg/mL.
4. The method for preparing fluorouracil pure drug nanoparticles according to claim 1, characterized in that the temperature in step S2 is stabilized at 65 ℃.
5. The method for preparing fluorouracil pure drug nanoparticles according to claim 1, characterized in that the pressure in step S2 is stabilized at 25MPa.
6. The method for preparing fluorouracil pure drug nanoparticles according to claim 1, characterized in that the rate in step S2 is 2mL/min.
7. The method for preparing fluorouracil pure drug nanoparticles according to claim 1, characterized in that the rate in step S3 is 1mL/min.
8. Fluorouracil drug-pure nanoparticle prepared by the method of any one of claims 1 to 7.
9. Use of fluorouracil pure drug nano-particles according to claim 8 in preparing medicines for inhibiting scar.
CN202310286091.9A 2023-03-22 2023-03-22 Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition Active CN116270479B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310286091.9A CN116270479B (en) 2023-03-22 2023-03-22 Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310286091.9A CN116270479B (en) 2023-03-22 2023-03-22 Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition

Publications (2)

Publication Number Publication Date
CN116270479A true CN116270479A (en) 2023-06-23
CN116270479B CN116270479B (en) 2024-05-31

Family

ID=86812936

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202310286091.9A Active CN116270479B (en) 2023-03-22 2023-03-22 Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition

Country Status (1)

Country Link
CN (1) CN116270479B (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130310424A1 (en) * 2011-01-31 2013-11-21 Mark William SURBER Aerosol pirfenidone and pyridone analog compounds and uses thereof
CN103655456A (en) * 2012-09-11 2014-03-26 上海交通大学医学院附属第九人民医院 Nanoscale alcohol liposome-carried 5-fluorouracil gel and preparation method thereof
CN110354097A (en) * 2019-07-19 2019-10-22 湖南大学 A kind of preparation method and applications of 5-Fluorouracil nano-drug preparation
CN110934875A (en) * 2019-12-20 2020-03-31 厦门大学 5-fluorouracil methotrexate double-drug preparation and preparation method thereof
CN114209871A (en) * 2021-10-29 2022-03-22 厦门大学 Preparation method of chemotherapy drug nanoparticle-iodized oil ultrastable homogeneous suppository

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130310424A1 (en) * 2011-01-31 2013-11-21 Mark William SURBER Aerosol pirfenidone and pyridone analog compounds and uses thereof
CN103655456A (en) * 2012-09-11 2014-03-26 上海交通大学医学院附属第九人民医院 Nanoscale alcohol liposome-carried 5-fluorouracil gel and preparation method thereof
CN110354097A (en) * 2019-07-19 2019-10-22 湖南大学 A kind of preparation method and applications of 5-Fluorouracil nano-drug preparation
CN110934875A (en) * 2019-12-20 2020-03-31 厦门大学 5-fluorouracil methotrexate double-drug preparation and preparation method thereof
CN114209871A (en) * 2021-10-29 2022-03-22 厦门大学 Preparation method of chemotherapy drug nanoparticle-iodized oil ultrastable homogeneous suppository

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
韩蕾;潘峰;陈庆华;: "有机溶剂移除工艺对微球性质及药物释放的影响", 中国医药工业杂志, no. 09, 10 September 2010 (2010-09-10), pages 692 - 697 *

Also Published As

Publication number Publication date
CN116270479B (en) 2024-05-31

Similar Documents

Publication Publication Date Title
US6623761B2 (en) Method of making nanoparticles of substantially water insoluble materials
EP2915557B1 (en) Retinoic acid microneedle
US7534453B1 (en) Cerium oxide nanoparticles and use in enhancing cell survivability
CN110368376A (en) A kind of Liraglutide sustained-release microspherical composition and preparation method thereof
Lin et al. Sulfasalazine-loaded nanoparticles for efficient inflammatory bowel disease therapy via ROS-scavenging strategy
CN109820824B (en) Capsaicin liquid crystal nano spray preparation for promoting skin wound healing and preparation method thereof
CN116270479B (en) Novel fluorouracil pure drug nano-particles and application thereof in scar inhibition
Peng et al. Microneedles for enhanced topical treatment of skin disorders: applications, challenges, and prospects
CN111658778B (en) Pharmaceutical composition, preparation method and application thereof
US20040126431A1 (en) Method for preparing microspheres containing a water-soluble substance
CN1919339B (en) Cucurbitacin nano preparation comprising protein, preparation method and use thereof
WO2004030661A2 (en) Therapeutic compositions comprising a boron-containing compound
KR20200099901A (en) Subcutaneous injection composition containing microparticles comprising finasteride
CN113577096B (en) Combined preparation for treating chronic wounds and preparation method thereof
KR102404224B1 (en) Biodegradable polymer microparticles containing sex hormone drugs and a method for manufacturing the same
CN102302459B (en) Preparation method of drug carried microsphere capable of being positioning injected into tumor cavity
CA2271657C (en) Androgen as a male contraceptive and non-contraceptive androgen replacement
Lengert et al. Novel formulation of glucocorticoid based on silver alginate microcapsules for intraarticular drug delivery
KR100853309B1 (en) Bio-degradable nanoparticles of polyDL-lactide-co-glycolide encapsulating ciprofloxacin HCl having extended-release properties, and manufacturing method thereof
CN114404369B (en) Dihydromyricetin nanocrystal and preparation method and application thereof
EP4371551A1 (en) Molecular assembly of bile acid or bile salt and pharmaceutical composition comprising same for removing local fat
CN107550887B (en) Compound nanometer preparation for treating T cell acute lymphoblastic leukemia, and preparation method and application thereof
EP1946746A1 (en) Particulate aqueous system for the preparation of a formulation for the treatment of adipose diseases
CN112972392B (en) Bilirubin nano-particles and preparation and application thereof
CN113712938B (en) V-9302 nano-particles for treating psoriasis and preparation method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant