CN112730278A - Mathematical modeling method for slow release of tea polyphenol drug-loaded microsphere drug - Google Patents
Mathematical modeling method for slow release of tea polyphenol drug-loaded microsphere drug Download PDFInfo
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- 239000003814 drug Substances 0.000 title claims abstract description 106
- 229940079593 drug Drugs 0.000 title claims abstract description 103
- 241001122767 Theaceae Species 0.000 title claims abstract description 58
- 150000008442 polyphenolic compounds Chemical class 0.000 title claims abstract description 52
- 235000013824 polyphenols Nutrition 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 44
- 239000004005 microsphere Substances 0.000 title claims abstract description 39
- 238000005538 encapsulation Methods 0.000 claims abstract description 6
- 238000013268 sustained release Methods 0.000 claims description 24
- 238000002835 absorbance Methods 0.000 claims description 17
- 239000012730 sustained-release form Substances 0.000 claims description 17
- OHZCFWMJMWFNFP-ZVGUSBNCSA-L (2r,3r)-2,3-dihydroxybutanedioate;iron(2+) Chemical compound [Fe+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O OHZCFWMJMWFNFP-ZVGUSBNCSA-L 0.000 claims description 13
- 230000001186 cumulative effect Effects 0.000 claims description 13
- 229940057006 ferrous tartrate Drugs 0.000 claims description 13
- 108010010803 Gelatin Proteins 0.000 claims description 9
- 229920000159 gelatin Polymers 0.000 claims description 9
- 239000008273 gelatin Substances 0.000 claims description 9
- 235000019322 gelatine Nutrition 0.000 claims description 9
- 235000011852 gelatine desserts Nutrition 0.000 claims description 9
- 238000005259 measurement Methods 0.000 claims description 9
- 229920001661 Chitosan Polymers 0.000 claims description 7
- 239000002077 nanosphere Substances 0.000 claims description 7
- 238000003491 array Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000004364 calculation method Methods 0.000 abstract description 6
- 239000000243 solution Substances 0.000 description 27
- 230000006399 behavior Effects 0.000 description 14
- 238000013270 controlled release Methods 0.000 description 14
- 230000008569 process Effects 0.000 description 10
- 230000002459 sustained effect Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 5
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000012876 carrier material Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000013178 mathematical model Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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Abstract
The invention provides a mathematical modeling method for slow release of tea polyphenol drug-loaded microsphere drugs, which comprises the following steps: s1, establishing a standard curved surface equation of tea polyphenol; s2, converting a formula to obtain a released drug concentration equation; s3, converting to obtain a release amount equation in the time period T; and S4, dividing the time T into enough small time periods with equal length to obtain an accumulated release amount equation, a dosage equation and an encapsulation rate. The mathematical modeling method for the slow release of the tea polyphenol drug-loaded microsphere drug re-models the drug slow release behavior of the tea polyphenol drug-loaded slow-release system, and explores a more accurate calculation model.
Description
Technical Field
The invention relates to the technical field of drug sustained-release modeling, in particular to a mathematical modeling method for sustained release of tea polyphenol drug-loaded microsphere drugs.
Background
In recent years, tea polyphenol has attracted more and more attention in the biomedical field due to its outstanding antioxidant property, antibacterial and antiviral property, and inhibitory effect on various tumor cells. But its characteristics of easy oxidation, easy absorption in the gastrointestinal tract environment and less entering the blood circulation limit its clinical application. The problem can be well solved by adopting the high molecular polymer to embed the tea polyphenol to prepare the microspheres or nanoparticles with the drug sustained and controlled release performance.
In the slow release process of the tea polyphenol drug-loaded slow release and control system, tea polyphenol is oxidized and deteriorated under the action of oxygen in the air, so that the error of the traditional method for quantitatively researching slow release behaviors is larger. Therefore, the drug slow-release behavior of the tea polyphenol drug-loaded slow-release and controlled-release system needs to be modeled again, a more accurate calculation model is explored, and a drug release dynamics model and principle of the drug-loaded system are analyzed from a mechanism. The controlled release system of the drug is divided into a slow release system and a controlled release system, wherein the slow release system is a system which can continuously release the drug in a longer time to achieve the purpose of prolonging the drug effect, and the controlled release system means that the drug can be released at a set speed in a set time to ensure that the blood concentration can be maintained in an effective concentration range for a long time. The final purpose of the drugs is to guide the drugs to be slowly released, maintain proper blood concentration for a long time, treat diseased regions and avoid drug toxicity caused by overhigh blood concentration.
In a sustained and controlled release system, controlling the proper release amount and release duration of the drug is a means for achieving the purposes of sustained release and controlled release. How to control the release behavior of the drug requires understanding of important factors affecting the release of the drug in the sustained/controlled release system. Firstly, the drug carrying mode is adopted, some drugs are added during production, and some drugs are carried in an adsorption mode, and the two modes necessarily lead to different slow release behaviors. Secondly, the molecular weight of the drug makes the drug have different sustained release curves in the sustained release process, macromolecules such as protein and the like have no serious burst release phenomenon in the release process, the release time is longer when the molecular weight is higher, and even the hydrophobicity of the drug is improved, so that the cumulative release rate of the drug is reduced and the like; the molecular weight of the drug is smaller, the phenomenon of burst release is easier to occur in the release process, and the total release time is shorter. Furthermore, the release behaviors of the hydrophilic drug and the hydrophobic drug are different, and when the hydrophilic drug is released in a human body, the hydrophilic drug is more easily released into a drug delivery system more quickly through the immersion of an aqueous solution, which brings higher initial release in the slow release process, and the hydrophobic drug is opposite. Meanwhile, the degradation speed of the carrier material has a great influence on the drug release behavior, for example, microspheres prepared by PLA have a longer release time compared with microspheres made of other materials. The selection of the drug and the carrier material can affect the release behavior of the sustained and controlled release system, even the particle size of the sustained and controlled release system can also affect the release behavior of the drug, generally, the larger the particle size, the higher the drug loading.
Knowing the relevant factors of drug release, it is necessary to study the release mechanism of the sustained and controlled release system after the drug is loaded in the system. The process of drug release is divided into two stages, firstly, after entering the human body, the drug on the surface of the system is firstly eroded by body fluid and dissolved out; the second stage is that the carrier is eroded and disintegrated, and the drug is released. The first stage of release corresponds to a diffusion process, usually referred to as the burst phase of the microspheres, and the second stage corresponds to an erosion process, usually referred to as the sustained release of the microspheres. Therefore, in order to describe these complex release behaviors in a unified way, it is a very necessary means to describe the drug release kinetics of the drug by mathematical modeling. The release kinetics can accurately describe the dynamic rule of the release amount of the drug and the change of the blood concentration by applying a principle and a mathematical model of the kinetics, and has important significance in clinical application. The release behavior of the sustained and controlled release system is described by measuring some important physical parameters, and after understanding the release phenomenon of all the affected systems, the release behavior of the system can be predicted even before the start of the measurement of the sustained release behavior, so that the prepared formula is optimized.
The existence of drug release kinetics enables the related research of the microspheres to objectively evaluate the release performance of the drug-loaded microspheres, provides suggestions for the design of a drug delivery system and a drug delivery scheme of the drug-loaded microspheres, and has important value in the clinical use of the microspheres, so the evaluation of the drug release kinetics of the microspheres is necessary.
Disclosure of Invention
The technical problem to be solved is as follows: the invention aims to provide a mathematical modeling method for slow release of tea polyphenol drug-loaded microspheres, which is used for modeling the drug slow release behavior of a tea polyphenol drug-loaded slow-release and controlled-release system again and exploring a more accurate calculation model.
The technical scheme is as follows: a mathematical modeling method for slow release of tea polyphenol drug-loaded microsphere drugs comprises the following steps:
s1, establishing a standard curved surface equation of tea polyphenol, wherein the standard curved surface equation is as follows:
λ＝ax+bt+c (1-1)
formula (1-1), wherein lambda is absorbance value, x is drug concentration, t is time, and a, b and c are equation coefficients; the concentration x and the time t of the drug are values set by the preparation solution when the standard curve is drawn, and can be set according to the concentration of the actually prepared drug-loaded microspheres and the sustained-release duration, wherein t is more than or equal to 0, and x is more than 0; the absorbance is a measured value, and lambda is more than or equal to 0; carrying out a series of measurement on the tea polyphenol standard concentration solution to obtain a series of arrays of x, t and lambda, and carrying out multiple regression treatment on the arrays by adopting SPSS software to obtain the values of coefficients a, b and c so as to obtain a tea polyphenol standard curved surface equation;
s2, converting the formula (1-1) to obtain a released drug concentration equation:
x＝(λ-bt-c)/a (1-2)
in the formula, x is the concentration of the drug, lambda is the absorbance value, t is the time, and a, b and c are equation coefficients;
s3, setting any period of time as T, setting the release amount in the period of time as Q, and combining the formula (1-2), the release amount in the period of time T is as follows:
Q＝v(λ-bT-c)/a (1-3)
in the formula, v is the drug release speed, x is the drug concentration, lambda is the absorbance value, T is any time period, and a, b and c are equation coefficients;
s4, dividing the time T into enough small time periods with equal length, namely n, wherein each small time period is delta T-T/n, and if the drug release amount in the time period from (i-1) delta T to i delta T is Q (T-1)i)
The cumulative amount released over this period of time, in conjunction with equations (1-3), can be:
Q(t1)+Q(t2)+......+Q(tn)＝v(λ-bnT/n-c)/a (1-4)
then when n → ∞ the time period Δ t → 0, i Δ t to (i +1) Δ t is almost equal to the same time instant, then the corresponding release time is: t-i Δ T ═ (n-i) Δ T (i ═ 0, 1. The amount released during this period from 0 to Δ t is Q (t)1) The release time is (n-i) Δ t ═ n Δ t. Then by (n-1) Δ t to n Δ t the amount released is Q (t)n)，The release time is (n-i) delta t ═ n- (n-1)]Δ t ═ Δ t, calculated as:
the above formula is simplified to obtain
S5, setting beta as the cumulative release rate, Qi(i 1, 2.... m.) release per time period, QeThe total amount of drug carried in the microspheres, when no release has occurred in the Nth measurement, then
If Q is setinitialThe dosage of the microspheres is the cumulative release rate
With an Encapsulation Efficiency (EE) of
Preferably, the tea polyphenol drug-loaded microspheres are tea polyphenol-chitosan/gelatin micro/nanospheres, and in order to eliminate the influence of gelatin dissolution on the absorption peak of tea polyphenol at 275nm in the slow release process, ferrous tartrate needs to be added into the slow release solution, so that the maximum absorption peak of the tea polyphenol slow release solution is shifted from 275nm to 540nm, and the influence of gelatin is eliminated.
Preferably, two methods can be adopted when the standard surface equation is established for tea polyphenol, which are respectively marked as method A and method B, wherein the method A is that ferrous tartrate is added until the absorbance of the tea polyphenol is detected after the tea polyphenol slow-release solution is collected, and the problem that the tea polyphenol is easily oxidized in the exposed air is solved by modeling of the method, and the standard surface equation established by adopting the method is lambda-0.008238 x-0.000245t + 0.002643; in the method B, a ferrous tartrate solution is added when a slow release solution is prepared, and for the method, the problem that a complex product of tea polyphenol and ferrous tartrate is easily oxidized when exposed to air is solved through modeling, and a standard surface equation established by the method is lambda-0.009029 x-0.0000531t + 0.000547.
Has the advantages that: the invention establishes a mathematical calculation model of the standard curved surface and the accumulative release rate of the tea polyphenol, solves the problem of influence on the accuracy of a measurement result due to easy oxidation of the tea polyphenol in the slow release process, and provides experimental basis and theoretical support for the research on the slow release performance of a drug-loaded slow-release and controlled-release system with the characteristic of easy variability of oxidation, decomposition and the like along with the change of time;
according to the medicine characteristics of the tea polyphenol, a binary primary standard surface equation of the tea polyphenol is established by taking the time as another independent variable while taking the concentration as the independent variable, a mathematical model is established for the cumulative release rate of the tea polyphenol in an in vitro release experiment by calculating the release amount of the medicine in a unit focusing on infinite hours, and a more accurate cumulative release rate calculation formula is given.
Detailed Description
Examples
A mathematical modeling method for slow release of tea polyphenol drug-loaded microsphere drugs comprises the following steps:
s1, establishing a standard curved surface equation of tea polyphenol, wherein the standard curved surface equation is as follows:
λ＝ax+bt+c (1-1)
formula (1-1), wherein lambda is absorbance value, x is drug concentration, t is time, and a, b and c are equation coefficients; the concentration x and the time t of the drug are values set by the preparation solution when the standard curve is drawn, and can be set according to the concentration of the actually prepared drug-loaded microspheres and the sustained-release duration, wherein t is more than or equal to 0, and x is more than 0; the absorbance is a measured value, and lambda is more than or equal to 0; carrying out a series of measurement on the tea polyphenol standard concentration solution to obtain a series of arrays of x, t and lambda, and carrying out multiple regression treatment on the arrays by adopting SPSS software to obtain the values of coefficients a, b and c so as to obtain a tea polyphenol standard curved surface equation;
s2, converting the formula (1-1) to obtain a released drug concentration equation:
x＝(λ-bt-c)/a (1-2)
in the formula, x is the concentration of the drug, lambda is the absorbance value, t is the time, and a, b and c are equation coefficients;
s3, setting any period of time as T, setting the release amount in the period of time as Q, and combining the formula (1-2), the release amount in the period of time T is as follows:
Q＝v(λ-bT-c)/a (1-3)
in the formula, v is the drug release speed, x is the drug concentration, lambda is the absorbance value, T is any time period, and a, b and c are equation coefficients;
s4, dividing the time T into enough small time periods with equal length, namely n, wherein each small time period is delta T-T/n, and if the drug release amount in the time period from (i-1) delta T to i delta T is Q (T-1)i)
The cumulative amount released over this period of time, in conjunction with equations (1-3), can be:
Q(t1)+Q(t2)+......+Q(tn)＝v(λ-bnT/n-c)/a (1-4)
then when n → ∞ the time period Δ t → 0, i Δ t to (i +1) Δ t is almost equal to the same time instant, then the corresponding release time is: t-i Δ T ═ (n-i) Δ T (i ═ 0, 1. The amount released during this period from 0 to Δ t is Q (t)1) The release time is (n-i) Δ t ═ n Δ t. Then by (n-1) Δ t to n Δ t the amount released is Q (t)n) The release time is (n-i) delta t ═ n- (n-1)]Δ t ═ Δ t, calculated as:
the above formula is simplified to obtain
S5, setting beta as the cumulative release rate, Qi(i 1, 2.... m.) release per time period, QeThe total amount of drug carried in the microspheres, when no release has occurred in the Nth measurement, then
If Q is setinitialThe dosage of the microspheres is the cumulative release rate
With an Encapsulation Efficiency (EE) of
The modeling method of the invention introduces a time variable in addition to a concentration variable in the drawing of a conventional unitary primary standard curve of the medicine, is used for solving the problem of inaccurate measurement caused by the reduction of absorbance value due to the oxidation of a tea polyphenol or a complex product of the tea polyphenol and ferrous tartrate along with the prolonging of exposure time in the in vitro slow release process, and not only introduces the time variable in an accumulative release rate calculation model, but also carries out infinitesimal segmentation on the time of sequentially dissolving and diffusing tea polyphenol molecules from the microcosmic view.
In the actual slow release test, when a certain amount of slow release solution is taken out at each time period to carry out an absorbance test, the rest solution needs to be completely sucked and emptied, and then fresh slow release solution is supplemented, which is different from the fact that only the test slow release solution is taken out in the general slow release test.
The present invention will be further described below by taking tea polyphenol-chitosan/gelatin micro/nanospheres as an example.
In this example, three different dosages of tea polyphenol-chitosan/gelatin micro/nanospheres were used, wherein the ratio of chitosan to gelatin was 2:10, and the dosages were 0.49%, 0.66%, 0.82%, 5%, and 9.1%, respectively. The method comprises the following specific steps:
1. the standard surface equation was determined and method B was used in this example, which added ferrous tartrate solution directly to the fresh sustained release solution. The standard surface equation is therefore λ 0.009029x-0.0000531t +0.000547
2. Preparing a ferrous tartrate solution: 1g of sodium potassium tartrate (C)4H4O6NaK·4H2O) and 5g ferrous sulfate (FeSO)4·7H2O) are respectively added into 1000mL of deionized water to prepare ferrous tartrate (C)4H4FeO6) And (3) solution.
3. Preparing a slow-release solution: every 50mL of the sustained-release solution contains 8mL of deionized water, 10mL of ferrous tartrate solution (the solution is prepared by using deionized water), and the rest is Phosphate Buffer Salt (PBS) solution.
4. Slow release experiments: putting a proper amount of drug-loaded micro/nanospheres into an 8k Da dialysis bag, and sealing the bag; putting the dialysis bag into a 100mL conical flask, and injecting 40mL of the sustained-release solution containing the ferrous tartrate into the flask; the Erlenmeyer flask was placed in a 37 ℃ incubator and shaken back and forth at a speed of 100 rpm/min. 5mL of the sustained release solution was collected at the indicated time points (0.5,1,6,24,36,48,72,84,96,144,192, 216h), while excess sustained release solution was aspirated, and the same volume of fresh sustained release solution was added. The collected sustained-release solution is stored in a sealed manner, and an absorbance test is carried out as soon as possible.
5. The release concentration and encapsulation efficiency of the tea polyphenol-chitosan/gelatin micro/nanospheres are shown in table 1.
TABLE 1 cumulative Release and encapsulation rates of tea polyphenols-Chitosan/gelatin micro/nanospheres
The parts which are not described in the invention can be realized by taking the prior art as reference.
On the basis of the slow release of the tea polyphenol drugs, the method can be used by the technical personnel in the field to research the loading and release behaviors of other similar tea polyphenol drugs.
It is intended that any equivalents, or obvious variations, which may be made by those skilled in the art in light of the teachings herein, be within the scope of the present invention.
Claims (3)
1. A mathematical modeling method for slow release of tea polyphenol drug-loaded microsphere drugs is characterized by comprising the following steps:
s1, establishing a standard curved surface equation of tea polyphenol, wherein the standard curved surface equation is as follows:
λ＝ax+bt+c (1-1)
formula (1-1), wherein lambda is absorbance value, x is drug concentration, t is time, and a, b and c are equation coefficients; the concentration x and the time t of the drug are values set by the preparation solution when the standard curve is drawn, and can be set according to the concentration of the actually prepared drug-loaded microspheres and the sustained-release duration, wherein t is more than or equal to 0, and x is more than 0; the absorbance is a measured value, and lambda is more than or equal to 0; carrying out a series of measurement on the tea polyphenol standard concentration solution to obtain a series of arrays of x, t and lambda, and carrying out multiple regression treatment on the arrays by adopting SPSS software to obtain the values of coefficients a, b and c so as to obtain a tea polyphenol standard curved surface equation;
s2, converting the formula (1-1) to obtain a released drug concentration equation:
x＝(λ-bt-c)/a (1-2)
in the formula, x is the concentration of the drug, lambda is the absorbance value, t is the time, and a, b and c are equation coefficients;
s3, setting any period of time as T, setting the release amount in the period of time as Q, and combining the formula (1-2), the release amount in the period of time T is as follows:
Q＝v(λ-bT-c)/a (1-3)
in the formula, v is the drug release speed, x is the drug concentration, lambda is the absorbance value, T is any time period, and a, b and c are equation coefficients;
s4, dividing the time T into enough tiny time periods with equal length, namely n, wherein each tiny time period is delta T equal to T/n, and if the time T is ordered to be the T/nThe amount of drug released during the period from (i-1) Δ t to i Δ t is
The cumulative amount released over this period of time, in conjunction with equations (1-3), can be:
Q(t1)+Q(t2)+……+Q(tn)＝v(λ-bnT/n-c)/a (1-4)
then when n → ∞ the time period Δ t → 0, i Δ t to (i +1) Δ t is almost equal to the same time instant, then the corresponding release time is: t-i Δ T ═ (n-i) Δ T (i ═ 0,1, … …, n). The amount released during this period from 0 to Δ t is Q (t)1) The release time is (n-i) Δ t ═ n Δ t. Then by (n-1) Δ t to n Δ t the amount released is Q (t)n) The release time is (n-i) delta t ═ n- (n-1)]Δ t ═ Δ t, calculated as:
the above formula is simplified to obtain
S5, setting beta as the cumulative release rate, Qi(i 1, 2.... m.) release per time period, QeThe total amount of drug carried in the microspheres, when no release has occurred in the Nth measurement, then
If Q is setinitialThe dosage of the microspheres is the cumulative release rate
With an Encapsulation Efficiency (EE) of
2. The mathematical modeling method for the slow release of the tea polyphenol drug-loaded microsphere drug according to claim 1, which is characterized in that: the tea polyphenol drug-loaded microspheres comprise tea polyphenol-chitosan/gelatin micro/nanospheres.
3. The mathematical modeling method for the slow release of the tea polyphenol drug-loaded microsphere drug according to claim 1, which is characterized in that: two methods can be adopted when the standard curved surface equation is established for tea polyphenol, which are respectively marked as a method A and a method B, wherein the method A is that ferrous tartrate is added until the absorbance of the tea polyphenol is detected after the tea polyphenol slow-release solution is collected, and the problem that the tea polyphenol is easy to oxidize when exposed to air is solved by modeling of the method, and the standard curved surface equation established by adopting the method is lambda-0.008238 x-0.000245t + 0.002643; in the method B, a ferrous tartrate solution is added when a slow release solution is prepared, and for the method, the problem that a complex product of tea polyphenol and ferrous tartrate is easily oxidized when exposed to air is solved through modeling, and a standard surface equation established by the method is lambda-0.009029 x-0.0000531t + 0.000547.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105044013A (en) * | 2015-08-07 | 2015-11-11 | 重庆理工大学 | Method for in vitro slow release performance evaluation of slow and controlled release preparation based on overflow principle |
| CN105963260A (en) * | 2016-06-27 | 2016-09-28 | 北京林业大学 | Preparation method of pH-sensitive type drug microspheres and pH-sensitive type drug microspheres prepared by preparation method |
| CN109187383A (en) * | 2018-04-08 | 2019-01-11 | 渤海大学 | Phytic acid content and the method for eliminating tea polyphenols interference in a kind of measurement mixed solution |
| CN109662957A (en) * | 2019-01-24 | 2019-04-23 | 太原理工大学 | A kind of preparation method for the polylactic acid/polyglycolic acid drug bearing microsphere for releasing the drug controllable |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105044013A (en) * | 2015-08-07 | 2015-11-11 | 重庆理工大学 | Method for in vitro slow release performance evaluation of slow and controlled release preparation based on overflow principle |
| CN105963260A (en) * | 2016-06-27 | 2016-09-28 | 北京林业大学 | Preparation method of pH-sensitive type drug microspheres and pH-sensitive type drug microspheres prepared by preparation method |
| CN109187383A (en) * | 2018-04-08 | 2019-01-11 | 渤海大学 | Phytic acid content and the method for eliminating tea polyphenols interference in a kind of measurement mixed solution |
| CN109662957A (en) * | 2019-01-24 | 2019-04-23 | 太原理工大学 | A kind of preparation method for the polylactic acid/polyglycolic acid drug bearing microsphere for releasing the drug controllable |
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