CN110063946A - A kind of chitosan sodium alginate micro ball preparation method and application for containing Ah pa and replacing Buddhist nun - Google Patents
A kind of chitosan sodium alginate micro ball preparation method and application for containing Ah pa and replacing Buddhist nun Download PDFInfo
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- CN110063946A CN110063946A CN201910312014.XA CN201910312014A CN110063946A CN 110063946 A CN110063946 A CN 110063946A CN 201910312014 A CN201910312014 A CN 201910312014A CN 110063946 A CN110063946 A CN 110063946A
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- buddhist nun
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- 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
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The invention discloses a kind of chitosan sodium alginate micro ball preparation method and applications for containing Ah pa and replacing Buddhist nun, the following steps are included: step 1: the alginate solution that the Ah pa of 10mg/mL is 0.0315% for Buddhist nun's solution, mass concentration being uniformly mixed according to the ratio that volume ratio is 1:23.5, obtains mixed solution A；Step 2: the calcium chloride solution that mass concentration is 0.2% being instilled in the mixed solution A that step 1 is prepared with the speed of 0.1ml/min, while stirring to get mixed solution B；Wherein mixed solution A and calcium chloride solution volume ratio are 24.5:1.5；Step 3: the chitosan solution that mass concentration is 0.07% being instilled in mixed solution B with the speed of 0.1ml/min, sufficiently after reaction, the required chitosan sodium alginate micro ball for containing Ah pa and replacing Buddhist nun is can be obtained in centrifugation, washing, vacuum freeze drying；The mixed solution B and chitosan solution volume ratio are 13:1；Microballoon of the present invention can promote drug in the absorption of enteron aisle；The absorption rate for improving drug can reduce the amount of being orally ingested of drug, reduce the side effect of drug bring.
Description
Technical field
The present invention relates to the preparations of sustained release agent, and in particular to a kind of chitosan sodium alginate micro ball system for containing Ah pa and replacing Buddhist nun
Preparation Method and application.
Background technique
A Pa is used as a kind of oral preparation for Buddhist nun (methanesulfonic acid Ah pa replaces Buddhist nun's piece), has treatment late gastric cancer, can extend trouble
The effect of the time-to-live of person；The ATP-binding site of the intracellular VEGFR-2 of its high competition has and blocks downstream signal transduction,
Inhibit the effect of tumor tissues new vascular generation.But since gastrointestinal tract rate is very fast, damage etc. of the gastric environment to drug
Cause human body few to drug absorption；It is 750mg that clinically Ah pa, which replaces everyone daily intake of Buddhist nun, at present, but this dosage is to trouble
Person causes the adverse reactions such as hypertension, albuminuria, hand-foot syndrome, influences recovery effects.Existing oral Ah pa for Buddhist nun due to
Destruction is absorbed in gastric environment, it is difficult to also possess curative effect of medication when reaching intestines environment, have office when treating intestines Cancerous disease
It is sex-limited；And Ah pa is at high cost for Buddhist nun, and daily higher intake will cause the financial burden of patient.
Summary of the invention
The present invention provide it is a kind of there is slow releasing function, Small side effects, can targeted therapy intestinal cancer the shell for containing Ah pa and replacing Buddhist nun
Glycan sodium alginate micro ball preparation method and application.
The technical solution adopted by the present invention is that: a kind of chitosan sodium alginate micro ball preparation method for containing Ah pa and replacing Buddhist nun,
The following steps are included:
Step 1: being according to volume ratio by the alginate solution that the Ah pa of 10mg/mL is 0.0315% for Buddhist nun's solution, mass concentration
The ratio of 1:23.5 is uniformly mixed, and obtains mixed solution A；
Step 2: the calcium chloride solution that mass concentration is 0.2% is mixed with what the speed instillation step 1 of 0.1ml/min was prepared
It closes in solution A, while stirring to get mixed solution B；Wherein mixed solution A and calcium chloride solution volume ratio are 24.5:1.5；
Step 3: the chitosan solution that mass concentration is 0.07% being instilled in mixed solution B with the speed of 0.1ml/min, sufficiently
After reaction, the required chitosan sodium alginate micro ball for containing Ah pa and replacing Buddhist nun is can be obtained in centrifugation, washing, vacuum freeze drying；Institute
It states mixed solution B and chitosan solution volume ratio is 13:1.
Further, in the chitosan solution, contain 1% acetic acid.
Further, chitosan solution stands 30min after being added dropwise in the step 3, is then centrifuged.
Further, 20min is centrifuged under the conditions of 12000 r/min in the step 3, and in triplicate.
Ah pa is contained for the application of the chitosan sodium alginate micro ball of Buddhist nun, the microballoon is used to prepare treatment intestines cancer
Targeted drug.
Further, the drug is oral preparation.
Further, the oral preparation it is one in containing Ah pa replace Buddhist nun 2mg.
The beneficial effects of the present invention are:
(1) the chitosan sodium alginate micro ball that the present invention is prepared can protect Ah pa not destroyed by gastric environment for Buddhist nun, promote medicine
Object achievees the effect that targeted therapy intestinal cancer in the absorption of enteron aisle；
(2) the chitosan sodium alginate micro ball that the present invention is prepared has pH sensibility, and the target area for improving drug absorbs
Utilization rate；
(3) the chitosan sodium alginate micro ball that the present invention is prepared can reduce the amount of being orally ingested of drug, reduce the financial burden,
Reduce the side effect of drug bring.
Detailed description of the invention
Fig. 1 is the absorbance figure that various concentration Ah pa replaces Buddhist nun's standard solution.
Fig. 2 is that the Ah pa that contains that the embodiment of the present invention is prepared replaces the chitosan sodium alginate micro ball of Buddhist nun in human body
Drug release patterns.
Specific embodiment
The present invention will be further described in the following with reference to the drawings and specific embodiments.
It prepares in accordance with the following methods and contains the chitosan sodium alginate micro ball that Ah pa replaces Buddhist nun, comprising the following steps:
Step 1: preparing the alginate solution that mass concentration is 0.0315%, be 0.07 wt% of 1% acetic acid containing mass concentration
Chitosan solution；It is respectively that two kinds of solution magnetic stirrer over night are spare；
Step 2: the Ah pa that compound concentration is 10 mg/mL replaces Buddhist nun's solution, and 10 mg Ah pas are dissolved in 1ml methanol solution for Buddhist nun；
It prepares obtained alginate solution with 23.5 ml steps 1 to mix, ultrasound is evenly dispersed to obtain mixed solution；
Step 3: the CaCl for being 0.2 wt% by 1.5 ml concentration using micro-injection pump2Solution is infused with the speed of 0.1 ml/min
Enter in the mixed solution obtained to step 2, while magnetic agitation；
Step 4: in the mixed solution that the step 3 that 2 ml chitosan solutions instill magnetic agitation is obtained, rate is 0.1 ml/
Min stands 30 min after being added dropwise to complete；12000 r/min high speed centrifugation, 20 min removes supernatant, milli-Q water microballoon；
After in triplicate, vacuum freeze drying is saved, and obtains the Ah pa that chitosan sodium alginate contains for Buddhist nun's Nano medication microsphere powder.
After tested according to the method described above, the chitosan sodium alginate being prepared contains Ah pa for the drugloading rate of Buddhist nun's microballoon
20%~25%.
It takes pictures through SEM, it can be seen that chitosan sodium alginate micro ball pattern, about 500 nm of microsphere diameter, hollow spherical cavity；
Microsphere diameter varies slightly after carrying medicine, and drug is present in inside spherical cavity.
A Pa replaces the concentration standard curve of Buddhist nun's drug as shown in Figure 1, preparing mass concentration respectively is 0.005 wt%, 0.01
Wt%, 0.015 wt%, 0.02 wt%, 0.025 wt%, 0.03 wt%, 0.035 wt%, the Ah pa of 0.04 wt% are molten for Buddhist nun's standard
Liquid, methanol are solvent；Using microplate reader detection characteristic wavelength be 348 nm at each strength solution absorbance value, obtain Ah
Pa replaces the drug concentration standard curve of Buddhist nun.
It is 1.2 by the pH that the powder microballoon after freeze-drying that portion is obtained according to above-mentioned preparation method is dissolved in 10 ml
In hydrochloric acid solution, drug simulated gastrointestinal environment extracorporeal releasing experiment is carried out.Delivery systme is put into 37 degree of shaking tables, 100 times/
Min, 20 mm of amplitude；System centrifuging and taking supernatant is detected into absorbance value at interval of 1 hour.
After release 4 hours, the microballoon being centrifuged is dissolved in the phosphate buffer that the pH of 10 ml is 7.4, simulates intestines
Liquid Environment release；It is discharged in same shaking table, sampling in each hour is primary, after release, utilizes microplate reader test sample Chinese medicine
Object Ah pa replaces the concentration of Buddhist nun, prepares In-vitro release curves (as shown in Figure 2).
From figure 2 it can be seen that medicine microspheres rest on stomach, and burst size is less 1~4 hour oral；In medication 5
Hour or so, medicine microspheres enter intestines environment, start a large amount of releases, drug release top occur at 8~9 hours；At this time
Drug substantially completely discharges, and is combined with enterocyte, plays curative effect of medication.
Cytotoxicity, the suppression of degradation rate and Human umbilical vein endothelial cells are carried out to drug bearing microsphere made from above-mentioned experiment
Ability processed is detected.Chitosan sodium alginate micro ball, which contains Ah pa, reduces the cytotoxicity of drug alone for Buddhist nun's microballoon, and
It can finally be degraded and absorbed, the growth of Human Umbilical Vein Endothelial Cells is inhibited.Illustrate the nanosphere of chitosan sodium alginate
The absorbability of drug and the toxicity to human body are only changed, it to be a kind of effective medicine that there is no the intrinsic effects for changing drug
Object contains mode.
Chitosan sodium alginate micro ball can protect drug and not destroyed by gastric environment, while have good biocompatibility
Can smooth degradation in vivo, drug can also be promoted in the absorption of enteron aisle, improve biological utilisation of drug during release
Rate.Chitosan sodium alginate micro ball has pH sensibility, can be improved the absorption rate of oral drugs.Chitosan sodium alginate
Microballoon is with the following functions as a kind of positively charged nanosphere:
(1) positively charged nanosphere in conjunction with electronegative enterocyte, can increase the intestines residence time of medicine microspheres；
(2) under acidic environment, chitosan sodium alginate micro ball swelling slows down, in conjunction with more closely, formed gel, prevent it from taking
The drug release of band；The nanosphere Fast-swelling under neutral and acidic environment, surface is loose and rough porous, promotes drug
Quick release；
(3) chitosan sodium alginate micro ball can be by the microorganism decomposition in small intestine, good biocompatibility, and hypotoxicity.
The present invention combines the medicament slow-release microsphere for containing Ah pa and replacing Buddhist nun using chitosan and sodium alginate, is used for intestines cancer
Target therapeutic agent.When medicine microspheres can enter gastric acid environment after oral administration (pH is about 1.2), microballoon is due to pH sensibility
And combining becomes close, and drug Ah pa is prevented to replace the release of Buddhist nun.When medicine microspheres are in digestion to intestines environment (pH is about 7.4),
Microballoon breakdown releases drug achievees the purpose that control release time.Microsphere surface and enterocyte carry out charge bonded, can promote
Enterocyte absorption of drugs increases the utilization efficiency of drug, reduces oral drugs and takes in dosage.
Existing to contain Ah pa for Buddhist nun's microballoon, mostly polymeric microballoon contains Ah pa for Buddhist nun's microballoon, this microballoon is used
In intravenous injection, only have the function of that slow release Ah pa replaces Buddhist nun, the characteristic without medicament selection Environment release；The present invention prolongs
It has grown Ah pa and has replaced Buddhist nun's drug residence time in vivo, haved the function that slow release, reduce the amount of being orally ingested of drug, drop
Its low bring side effect；Gastric environment absorption of drugs is reduced, so that drug is mainly reached intestines position, reaches targeted therapy intestines
The effect of cancer.
Claims (7)
1. a kind of chitosan sodium alginate micro ball preparation method for containing Ah pa and replacing Buddhist nun, which comprises the following steps:
Step 1: by the Ah pa of 10mg/mL for Buddhist nun's solution, mass concentration be 0.0315% alginate solution according to volume ratio
It is uniformly mixed for the ratio of 1:23.5, obtains mixed solution A；
Step 2: the calcium chloride solution that mass concentration is 0.2% is mixed with what the speed instillation step 1 of 0.1ml/min was prepared
It closes in solution A, while stirring to get mixed solution B；Wherein mixed solution A and calcium chloride solution volume ratio are 24.5:1.5；
Step 3: the chitosan solution that mass concentration is 0.07% being instilled in mixed solution B with the speed of 0.1ml/min, sufficiently
After reaction, the required chitosan sodium alginate micro ball for containing Ah pa and replacing Buddhist nun is can be obtained in centrifugation, washing, vacuum freeze drying；Institute
It states mixed solution B and chitosan solution volume ratio is 13:1.
2. a kind of chitosan sodium alginate micro ball preparation method for containing Ah pa and replacing Buddhist nun, feature exist according to claim 1
In containing 1% acetic acid in the chitosan solution.
3. a kind of chitosan sodium alginate micro ball preparation method for containing Ah pa and replacing Buddhist nun according to claim 1, feature
It is, chitosan solution stands 30min in the step 3 after being added dropwise, and is then centrifuged.
4. a kind of chitosan sodium alginate micro ball preparation method for containing Ah pa and replacing Buddhist nun according to claim 1, feature
It is, is centrifuged 20min in the step 3 under the conditions of 12000r/min, and in triplicate.
5. what is be prepared as described in claim 1-4 contains Ah pa for the application of the chitosan sodium alginate micro ball of Buddhist nun, spy
Sign is that the microballoon is used to prepare the targeted drug for the treatment of intestines cancer.
6. application according to claim 5, which is characterized in that the drug is oral preparation.
7. application according to claim 6, which is characterized in that replace Buddhist nun 2mg containing Ah pa during the oral preparation is one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910312014.XA CN110063946A (en) | 2019-04-18 | 2019-04-18 | A kind of chitosan sodium alginate micro ball preparation method and application for containing Ah pa and replacing Buddhist nun |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910312014.XA CN110063946A (en) | 2019-04-18 | 2019-04-18 | A kind of chitosan sodium alginate micro ball preparation method and application for containing Ah pa and replacing Buddhist nun |
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| CN110063946A true CN110063946A (en) | 2019-07-30 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114948911A (en) * | 2022-06-17 | 2022-08-30 | 佛山市中医院 | Traumatology oil sustained-release microcapsule and preparation method thereof |
| CN115057741A (en) * | 2022-07-04 | 2022-09-16 | 西南交通大学 | Preparation method of calcium alginate-chitosan microbead slow-release fertilizer difficult to swell |
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| US20090162440A1 (en) * | 2007-12-19 | 2009-06-25 | Beijing Shengyiyao Science & Technology Development Co., Ltd. | Sodium alginate microsphere vascular embolus containing water-soluble drug and preparation and application thereof |
| CN108354902A (en) * | 2018-05-22 | 2018-08-03 | 杭州市肿瘤医院 | A kind of Ah pa is for Buddhist nun's polymer micelle and preparation method thereof |
| CN109381436A (en) * | 2017-08-14 | 2019-02-26 | 江苏恒瑞医药股份有限公司 | A Pa is for Buddhist nun's pharmaceutical composition and preparation method thereof |
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| CN1745848A (en) * | 2005-07-29 | 2006-03-15 | 中国人民解放军第三军医大学 | Chitin-sodium alginate packed pylorus helicobacterium protein microballs and their preparation |
| US20090162440A1 (en) * | 2007-12-19 | 2009-06-25 | Beijing Shengyiyao Science & Technology Development Co., Ltd. | Sodium alginate microsphere vascular embolus containing water-soluble drug and preparation and application thereof |
| CN109381436A (en) * | 2017-08-14 | 2019-02-26 | 江苏恒瑞医药股份有限公司 | A Pa is for Buddhist nun's pharmaceutical composition and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114948911A (en) * | 2022-06-17 | 2022-08-30 | 佛山市中医院 | Traumatology oil sustained-release microcapsule and preparation method thereof |
| CN114948911B (en) * | 2022-06-17 | 2024-02-09 | 佛山市中医院 | Wound oil slow-release microcapsule and preparation method thereof |
| CN115057741A (en) * | 2022-07-04 | 2022-09-16 | 西南交通大学 | Preparation method of calcium alginate-chitosan microbead slow-release fertilizer difficult to swell |
| CN115057741B (en) * | 2022-07-04 | 2023-06-20 | 西南交通大学 | Preparation method of calcium alginate-chitosan microsphere slow-release fertilizer not easy to swell |
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