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CN119438324A - Method for determining the dispersibility of pharmaceutical agents on slime - Google Patents

Method for determining the dispersibility of pharmaceutical agents on slime Download PDF

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Publication number
CN119438324A
CN119438324A CN202310987108.3A CN202310987108A CN119438324A CN 119438324 A CN119438324 A CN 119438324A CN 202310987108 A CN202310987108 A CN 202310987108A CN 119438324 A CN119438324 A CN 119438324A
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mixture
slime
current intensity
point
real
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Inventor
赵玥
王金华
孙飞
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Sinopec Petrochemical Research Institute Co ltd
China Petroleum and Chemical Corp
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Sinopec Petrochemical Research Institute Co ltd
China Petroleum and Chemical Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38Diluting, dispersing or mixing samples

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  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

The invention relates to the technical field of water treatment, and discloses a method for measuring the dispersion performance of a medicament on slime. The method comprises the steps of (1) carrying out first mixing on water and clay to obtain a mixture I, under a standing condition, adopting a real-time automatic in-situ monitoring device to measure the current intensity received by the mixture I at the moment t, (2) carrying out second mixing on the mixture I and a medicament to be tested to obtain a mixture II, under the standing condition, adopting the real-time automatic in-situ monitoring device to measure the current intensity received by the mixture II at the moment t, (3) calculating to obtain the turbidity of the mixture I and the turbidity of the mixture II at the moment t through a formula (I), and (4) calculating to obtain the dispersion rate of the medicament to be tested at the moment t through a formula (II). The method provided by the invention has the advantages of simple operation, can realize in-situ monitoring and automatic recording of test data, and greatly improves the precision of a dispersion rate calculation result and the accuracy of an evaluation result.

Description

Method for measuring dispersion property of medicament to slime
Technical Field
The invention relates to the technical field of water treatment, in particular to a method for measuring the dispersion performance of a medicament on slime.
Background
The generation of biological slime is a common problem in circulating cooling water systems. The heat exchange efficiency of the heat exchanger and the cooling efficiency of the cooling tower are reduced, the water quality is deteriorated, the local corrosion of equipment is accelerated, and finally the running cost of the system is increased and the service life of the system is shortened.
The use of a slime stripper to strip slime that has grown on equipment and pipe walls is a common slime control method. After the high-concentration slime stripping agent is added in an impact manner, circulating water stays in the system for a certain time, and when the turbidity of the circulating water reaches the highest, a large amount of sewage is discharged, and a large amount of fresh water is replenished. The slime stripping property of the medicament is a main index for inspecting the control performance of the medicament slime.
At present, in order to respond to the call of energy conservation, water conservation and emission reduction of petrochemical enterprises, the slime stripping scheme of the enterprises is gradually changed from 'large amount of pollution discharge and large amount of water supplement' to 'small amount of pollution discharge and small amount of water supplement'. However, when the enterprise implements the scheme of 'less discharge and less supplement', it is found that, due to slower pollution discharge and less pollution discharge, some stripped slime can redeposit on the surfaces of equipment and pipelines, resulting in secondary damage. Maintaining the dispersibility of the released slime is a problem that needs to be addressed at the present stage. The dispersibility of the slime treatment agent is changed from the property of "auxiliary peeling" to the property of the agent that needs to be considered with great importance.
Currently, the commonly used methods for evaluating the dispersibility of the medicament slime include a kaolin dispersing method and a slime dispersing method. The kaolin dispersion method tests the dispersibility of the agent to kaolin. A certain amount of kaolin mother liquor and a certain concentration of medicament are added and fully stirred in a constant temperature water bath at 55 ℃. After standing, the supernatant was collected, and the absorbance of the supernatant was determined at 420nm using a spectrophotometer using a 3cm cuvette. The higher the absorbance, the better the dispersion of the agent. However, since kaolin has a higher density than biological slime and is not sticky, experimental results have a larger error. And the clay dispersion rule replaces kaolin with culture clay, so that the experiment can better represent the condition of industrial field circulating water.
At present, the slime dispersing method is a more commonly used slime dispersing agent performance evaluation method.
However, the current slime dispersion methods also have significant drawbacks. First, although the weight of the added slime was consistent for each test, the initial turbidity of the non-added slime was different due to non-uniformity of the cultured slime. This results in poor accuracy, reproducibility and precision in evaluating the dispersion properties of the pharmaceutical agent using the method, and in addition, the operation of "sucking up the supernatant to measure absorbance" is highly subjective, and the positions where different operators or the same operator suck up different samples may be different, which further increases the error of the analysis result of the method, reduces the accuracy and precision of the method, and finally, since the absorbance measurement of the supernatant is an off-site measurement, there is a time difference in the absorbance of the supernatant from the end of the rest to the measurement, which results in that the time of each set of experiments is not completely equal when a plurality of sets of experiments are simultaneously performed. This also affects the reproducibility and precision of the process.
In summary, in the background where the dispersibility of a chemical to a slime becomes a key evaluation property, it is required to provide a better method for evaluating the dispersibility of a chemical to a slime.
Disclosure of Invention
The invention aims to overcome the defects of large influence of human operation errors and poor accuracy and precision of the traditional method for evaluating the dispersion performance of the medicament on the slime, and provides a novel method with good accuracy and high precision.
In order to achieve the above object, the present invention provides a method for measuring dispersibility of a drug to a slime, the method comprising:
(1) Under a standing condition, measuring the current intensity I kt received by the M point of the mixture I at the moment t by adopting a real-time automatic in-situ monitoring device;
(2) Under a standing condition, measuring the current intensity I jt received by the M point of the mixture II at the moment t by adopting a real-time automatic in-situ monitoring device;
(3) Calculating to obtain the turbidity TU kt of the mixture I and the turbidity TU jt of the mixture II at the time t through a formula (I);
TU= -l -1×ln(It/I0) equation (I);
(4) Calculating to obtain the dispersion rate D of the medicament to be detected at the moment t through a formula (II);
d= (TU jt-TUkt)/TUkt formula (II);
the point M is a point which is vertically spaced from the lower part of the upper liquid surface of the mixture I or the mixture II by 1-3 mm;
wherein in the formula (I) and the formula (II),
L represents the distance from a laser emitting point to a laser receiving point in the real-time automatic in-situ monitoring device, and the unit is cm;
I t represents the current intensity of a laser receiving point at the moment t in the real-time automatic in-situ monitoring device, and the unit is mA;
i 0 represents the current intensity of a laser emission point in the real-time automatic in-situ monitoring device, and the unit is mA.
When the method provided by the invention is used for evaluating the dispersion performance of the medicament on the slime, the influence of uneven slime samples on medicament evaluation can be effectively eliminated, and the manual operation error can be reduced. Meanwhile, the method provided by the invention has the advantage of simple and convenient operation, and the whole operation process can realize in-situ monitoring and automatic recording of test data, thereby greatly improving the precision of a dispersion rate calculation result and the accuracy of an evaluation result.
Drawings
FIG. 1 is a schematic illustration of a preferred real-time automatic in-situ monitoring apparatus provided by the present invention;
Fig. 2 is a graph showing the results of fitting the current intensity data for mixture I of dodecyl dimethyl benzyl ammonium chloride as the test agent in example 1 provided by the present invention.
Description of the reference numerals
1-Laser emitter 2-Container A3-Container B
4-Stirrer 5-temperature-control magnetic heating stirrer
6-Silicon photodiode 7-data collector
8-Computer
Detailed Description
The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.
As described above, the present invention provides a method of determining the dispersibility of a pharmaceutical agent to a slime, the method comprising:
(1) Under a standing condition, measuring the current intensity I kt received by the M point of the mixture I at the moment t by adopting a real-time automatic in-situ monitoring device;
(2) Under a standing condition, measuring the current intensity I jt received by the M point of the mixture II at the moment t by adopting a real-time automatic in-situ monitoring device;
(3) Calculating to obtain the turbidity TU kt of the mixture I and the turbidity TU jt of the mixture II at the time t through a formula (I);
TU= -l -1×ln(It/I0) equation (I);
(4) Calculating to obtain the dispersion rate D of the medicament to be detected at the moment t through a formula (II);
d= (TU jt-TUkt)/TUkt formula (II);
the point M is a point which is vertically spaced from the lower part of the upper liquid surface of the mixture I or the mixture II by 1-3 mm;
wherein in the formula (I) and the formula (II),
L represents the distance from a laser emitting point to a laser receiving point in the real-time automatic in-situ monitoring device, and the unit is cm;
I t represents the current intensity of a laser receiving point at the moment t in the real-time automatic in-situ monitoring device, and the unit is mA;
i 0 represents the current intensity of a laser emission point in the real-time automatic in-situ monitoring device, and the unit is mA.
It should be noted that, in the present invention, the M point of the mixture I and the M point of the mixture II represent that the two tests in the step (1) and the step (2) are performed at the same position of the mixture, and the position of the test is a point having a vertical distance of 1 to 3mm below the liquid surface on the mixture I or the mixture II.
The inventors of the present invention found that the dispersion result calculated in the preferred case where the current intensity I kt at time t and the current intensity I jt at time t are calculated by fitting a unitary six-degree function to the current intensity data at all times in the test period using a unitary six-degree function has higher precision.
In the invention, the fitting of the monobasic six-order function can be performed by adopting a fitting function in Microsoft Excel software. When fitting is performed by adopting a unitary six-degree function, the method has accuracy and easy operability. When the fitting is performed by using a function of a higher number of times, the accuracy of the result can be further improved in a certain range, but the complex calculation is required, and the method has the advantage of no easy operation.
Fig. 2 is a graph showing the results of fitting the current intensity data for mixture I of dodecyl dimethyl benzyl ammonium chloride as the test agent in example 1 provided by the present invention. The rest of fitting result graphs of current intensity data obtained by fitting the unitary sixth-order polynomial function are similar to the fitting result graphs, and the fitting result graphs of the current intensity data when the mixture I of the drug to be tested in the embodiment 1 is dodecyl dimethyl benzyl ammonium chloride are exemplarily provided in the invention.
In fig. 2, a plot of current values (mA) recorded per second is plotted on the abscissa with test time (seconds, s) as the ordinate. The current intensity at any test time was calculated using the unitary sixth function (y= -1E-24x 6+7E-20x5-1E-15x4+1E-11x3-6E-8x2 +2E-4x + 0.3189) fitted in fig. 2 for mixture I when the agent to be tested in example 1 was dodecyldimethylbenzyl ammonium chloride.
Preferably, the slime is used in an amount of 1g-4g relative to 1L of the water.
Preferably, the amount of the drug to be measured is 10mg to 100mg in terms of the effective ingredient relative to 1L of the water.
According to another preferred embodiment, the method further comprises:
The real-time automatic in-situ monitoring device comprises a laser emission unit, a sample reaction unit, a photoelectric conversion unit, a data acquisition unit and a data processing unit.
Preferably, the laser emission unit comprises a laser emitter with the wavelength of 492-577nm and the power of 12-15 mW. The inventor of the present invention found that when the wavelength is greater than 577nm, the laser light has too strong penetrability, and the sensitivity to the particles in the mixture I or the mixture II is insufficient, so that the change of the light transmittance of the mixture I or the mixture II upper layer solution along with the sedimentation time cannot be effectively reflected, and when the wavelength is less than 492nm, the laser light cannot penetrate the mixture I or the mixture II, so that the light transmittance of the mixture I or the mixture II upper layer solution cannot be effectively measured.
In the present invention, the stationary condition is a continuous process. And after the mixture is stood for a period of time, part of suspended matters begin to subside, the laser passing rate of the upper layer solution is gradually increased, and the dispersion performance of different medicaments on the slime is evaluated by recording the change of the laser passing rate of the upper layer solution. After standing for the same time, the lower the laser passing rate is, which indicates that the better the dispersion performance of the medicament on the slime is.
Preferably, the photoelectric conversion unit includes a silicon photodiode. The silicon photodiode is capable of converting a laser signal emitted from a laser emitter and penetrating either mixture I or mixture II into a current signal. The higher the laser signal, the higher the current signal. The output current signal is collected by the connected data collection unit at a frequency of once per second, the turbidity of the mixture I or the turbidity of the mixture II are obtained through calculation of the data processing unit, and the dispersion rate of the medicament to the slime is further obtained through conversion.
The specific kind of the slime is not particularly limited as long as the slime can be made to have the same or similar properties as those of the slime in the actual circulating water. The following of the invention provides by way of example a particularly preferred embodiment, which should not be construed as limiting the invention.
According to a particularly preferred embodiment, the method further comprises:
The slime is culture slime, and the culture slime is prepared by a method comprising the following steps:
And adopting a water cooling tower device to carry out dynamic simulation experiments.
Preferably, the conditions of the dynamic simulation experiment comprise that the temperature is 30-35 ℃, the circulating water flow is 60-70L/h, and the nutrient solution is added every 24-36 h.
The type of the circulating water in the dynamic simulation experiment is not particularly limited, and for example, ca 2+、Na+、Cl-、SO4 2-、HCO3 - and the like may be contained in the circulating water.
Preferably, the nutrient solution contains glucose, ammonium chloride, magnesium sulfate, potassium chloride, yeast extract, and sodium dihydrogen phosphate.
More preferably, in the nutrient solution, the content of glucose is 0.45-0.55g/L, the content of ammonium chloride is 1.5-2.5g/L, the content of magnesium sulfate is 0.08-0.15g/L, the content of potassium chloride is 0.2-0.3g/L, the content of yeast extract is 0.18-0.22g/L, and the content of sodium dihydrogen phosphate is 0.8-1.0g/L.
The structure of the water cooling tower device is not particularly limited, and the water cooling tower device can be various water cooling tower devices sold in the market or assembled and built by oneself.
Preferably, the conditions of the first mixing and the second mixing are the same, including under magnetic stirring conditions, and stirring speed is 200-300rpm, stirring time is 15-60min, and temperature is 30-35 ℃. The same conditions of the first mixing and the second mixing can ensure that the initial turbidity of the slime in the mixture I and the initial turbidity of the slime in the mixture II are the same to the greatest extent, so that adverse effects on test results caused by non-uniformity of slime samples in the existing method can be reduced.
In the invention, the magnetic stirring device has the following advantages compared with other mixing devices such as manual mixing and a shaking table and the like:
The magnetic stirrer has the advantages of small occupied area, convenient operation, good mixing effect and test repeatability in the mixing process, and is favorable for building an in-situ test device. If the manual mixing method is used, the mixing of each test is not repeatable, and if the mixing is performed by using other equipment such as a shaking table, the setting up of an in-situ experimental device is difficult due to the overlarge occupied area of the other equipment such as the shaking table.
According to a particularly preferred embodiment, the agent to be tested in step (2) is added in situ to the sample reaction unit for a second mixing with mixture I. In the preferred case, the absolute positions of the laser transmitter in the laser transmitting unit, the sample reaction unit and the silicon photodiode in the photoelectric conversion unit are not changed during the medicament test, and the adverse effect of the step of manually sucking the supernatant to measure absorbance on the test accuracy and precision in the existing method is fundamentally eliminated.
Preferably, the standing condition comprises a temperature of 30-35 ℃ and a time of 3-5h.
The method of the present invention is further described below with reference to fig. 1, but the present invention is not limited thereto.
FIG. 1 is a schematic diagram of a preferred real-time automatic in-situ monitoring device provided by the present invention. According to the method, water and/or a medicament to be tested and slime are/is placed in a container A2 in a container B3 filled with water in a sample reaction unit, a temperature-control magnetic heating stirrer 5 is started to enable a magnetic stirrer 4 to rotate for mixing, under a standing condition, laser emitted by a laser emitter 1 in a laser emission unit passes through a point M of a mixture I or a mixture II, is received by a silicon photodiode 6 in a photoelectric conversion unit and is converted into a current signal, the current signal is collected through a data collector 7 in a data collection unit, the current intensity is obtained, and then the dispersion rate of the medicament to be tested is calculated through a computer 8 in a data processing unit.
The invention will be described in detail below by way of examples.
In the following examples, all the raw materials used were commercially available products unless otherwise specified.
In the following examples, unless otherwise specified, the wavelength of the laser emitter used was 532nm, the power was 13.6mW, the current intensity I 0 at the laser emitting point was 3.4247mA, the distance l from the laser emitting point to the laser receiving point was 30cm, and the magnetic stirrer had a specification of 650mm.
Raw materials:
yeast paste purchased from Aba Ding Gongsi.
Isothiazolinones are available from Shandong Tai and technology Co., ltd.
Glutaraldehyde, available from water treatment technology limited company for mao-name and national song.
Dodecyl dimethyl benzyl ammonium chloride available from Shandong Tai and technology Co., ltd.
Tetradecyldimethylbenzyl ammonium chloride, commercially available from the scientific and technological company of Bacilengcarb, beijing.
Preparation of slime
The preparation of circulating water, namely taking water from the site for test, wherein the specific water quality is that the total alkalinity is 150mg/L, the calcium hardness is 800mg/L, the chloride ion content is 800mg/L, and the sulfate ion content is 200mg/L;
Preparing a nutrient solution by using water as a solvent, wherein the nutrient solution comprises 0.5g/L of glucose, 2.0g/L of ammonium chloride, 0.1g/L of magnesium sulfate, 0.25g/L of potassium chloride, 0.2g/L of yeast extract and 1.0g/L of sodium dihydrogen phosphate;
adding the circulating water into a water tank of a cooling tower device for dynamic simulation experiments to obtain culture slime;
the dynamic simulation experiment is carried out under the conditions that the temperature is 34 ℃, the circulating water flow is 65L/h, and 2L of the nutrient solution is added every 24 h.
Example 1
(1) Under a standing condition, measuring the current intensity I kt received by the M point of the mixture I at the moment t by adopting a real-time automatic in-situ monitoring device in FIG. 1;
(2) The mixture I and 2.5mg of the medicament to be detected (calculated by active ingredients) are subjected to second mixing to obtain a mixture II, and under a standing condition, the current intensity I jt received by the M point of the mixture II at the moment t is measured by adopting a real-time automatic in-situ monitoring device in FIG. 1;
the current intensity I kt at the time t and the current intensity I jt at the time t are obtained by adopting a unitary sixth function calculation obtained by fitting current intensity data at all times in a test time period;
(3) Calculating to obtain the turbidity TU kt of the mixture I and the turbidity TU jt of the mixture II at the time t through a formula (I);
TU= -l -1×ln(It/I0) equation (I);
(4) Calculating to obtain the dispersion rate D of the medicament to be measured on the slime at the moment t through a formula (II), repeating for 3 times, wherein the specific result is shown in a table 1;
d= (TU jt-TUkt)/TUkt formula (II);
The point M is a point which is 2mm away from the vertical distance below the upper liquid level of the mixture I or the mixture II;
The first mixing and the second mixing are carried out under the magnetic stirring condition, the stirring speed is 250rpm, the stirring time is 30min, and the temperature is 32 ℃;
the standing condition is that the temperature is 32 ℃ and the time is 4 hours.
Example 2
This example was conducted in a similar manner to example 1 except that:
The laser emitter in the real-time automatic in-situ monitoring device in fig. 1 was replaced with a laser emitter with a wavelength of 405nm and a power of 6.7mW, and the other conditions were the same as in example 1, and repeated 3 times, and the specific results are shown in table 1.
Example 3
This example was conducted in a similar manner to example 1 except that:
the current intensities I kt at time t and I jt at time t were not fitted using a unitary six-degree function, the other conditions were the same as in example 1, and were repeated 3 times, with the specific results shown in table 1.
Comparative example 1
This comparative example was conducted in a similar manner to example 1 except that:
The M point in the step (1) and the step (2) is a point which is 20mm in vertical distance from the upper liquid surface of the mixture I or the mixture II, the other conditions are the same as in the example 1, and the specific results are shown in Table 1.
Comparative example 2
This comparative example uses the method referred to in the "study of microbial dispersion technology" published by Chen Chao in 2012 to evaluate the dispersion properties of a pharmaceutical agent on slime, specifically as follows:
Taking 6 conical flasks of 250mL, adding 0.500g of slime (accurate to +/-0.001 g) and 250mL of deionized water into the conical flasks, shaking the conical flasks uniformly at 200rpm by using a shaking table for 30min, wherein one conical flask is not added with a medicament to be tested so as to be used as a blank control, and adding one of the medicaments to be tested, namely isothiazolinone, glutaraldehyde, dodecyl dimethyl benzyl ammonium chloride and tetradecyl dimethyl benzyl ammonium chloride (the effective concentration is 10 mg/L) into the other conical flasks respectively;
Shaking by a shaking table at 200rpm for 30min, and standing in an incubator at 32 ℃. After standing for 4 hours, the supernatant was sucked with a dropper, absorbance of the supernatant at 420nm was detected, and the dispersion D' of the reagent to be measured was calculated using the formula (III), and repeated 3 times, with the specific results shown in Table 2.
D' = (A-A 0)/A0 ×100% formula (III)
TABLE 1
Note that the dispersion ratios in table 1 are values calculated at time t=4h, and the coefficient of variation c·v=standard deviation/mean value×100%, wherein when the data are positive and negative at the same time, the coefficient of variation is not calculated, and the comparative meaning is not obtained.
Table 1, below
TABLE 2
As can be seen from the results of Table 1, the results obtained in 3 repeated tests in example 1 are isothiazolinone < glutaraldehyde < tetradecyldimethylbenzyl ammonium chloride < dodecyldimethylbenzyl ammonium chloride, which is consistent with the ranking of the dispersibility of the 4 agents to be tested on slime in practical application, and the method provided by the invention has higher accuracy, and the variation coefficient of 3 repeated tests in example 1 is about 5%, and the method provided by the invention has higher precision (i.e. repeatability).
However, the results obtained in 3 replicates of comparative example 2 were different, while the coefficient of variation in 3 replicates of comparative example 2 was up to 61.02%. From the 3 repeated experiments of comparative example 2, it was not possible to determine whether glutaraldehyde had a dispersing effect or not, and whether tetradecyldimethylbenzyl ammonium chloride had a dispersing effect superior to that of dodecyldimethylbenzyl ammonium chloride or not, and it was not possible to accurately evaluate the dispersibility of the existing agent to slime.
In summary, compared with the existing method for evaluating the dispersing performance of the medicament on the slime, the method provided by the invention has higher accuracy and better precision when being used for evaluating the dispersing performance of the medicament on the slime.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, a number of simple variants of the technical solution of the invention are possible, including combinations of the individual technical features in any other suitable way, which simple variants and combinations should likewise be regarded as being disclosed by the invention, all falling within the scope of protection of the invention.

Claims (10)

1. A method of determining the dispersion of a pharmaceutical agent in a slurry, the method comprising:
(1) Under a standing condition, measuring the current intensity I kt received by the M point of the mixture I at the moment t by adopting a real-time automatic in-situ monitoring device;
(2) Under a standing condition, measuring the current intensity I jt received by the M point of the mixture II at the moment t by adopting a real-time automatic in-situ monitoring device;
(3) Calculating to obtain the turbidity TU kt of the mixture I and the turbidity TU jt of the mixture II at the time t through a formula (I);
TU= -l -1×ln(It/I0) equation (I);
(4) Calculating to obtain the dispersion rate D of the medicament to be measured on the slime at the moment t through a formula (II);
d= (TU jt-TUkt)/TUkt formula (II);
the point M is a point which is vertically spaced from the lower part of the upper liquid surface of the mixture I or the mixture II by 1-3 mm;
wherein in the formula (I) and the formula (II),
L represents the distance from a laser emitting point to a laser receiving point in the real-time automatic in-situ monitoring device, and the unit is cm;
I t represents the current intensity of a laser receiving point at the moment t in the real-time automatic in-situ monitoring device, and the unit is mA;
i 0 represents the current intensity of a laser emission point in the real-time automatic in-situ monitoring device, and the unit is mA.
2. The method of claim 1, wherein the method further comprises:
the current intensity I kt at time t and the current intensity I jt at time t are calculated by fitting a unitary sixth function to the current intensity data at all times during the test period.
3. The method according to claim 1 or 2, wherein the method further comprises:
The real-time automatic in-situ monitoring device comprises a laser emission unit, a sample reaction unit, a photoelectric conversion unit, a data acquisition unit and a data processing unit.
4. A method according to claim 3, wherein the laser emitting unit comprises a laser emitter with a wavelength of 492-577nm and a power of 12-15 mW.
5. The method according to claim 3 or 4, wherein the photoelectric conversion unit contains a silicon photodiode therein.
6. The method according to any one of claims 1-5, wherein the method further comprises:
The slime is culture slime, and the culture slime is prepared by a method comprising the following steps:
And adopting a water cooling tower device to carry out dynamic simulation experiments.
7. The method according to claim 6, wherein the conditions of the dynamic simulation experiment comprise a temperature of 30-35 ℃, a circulating water flow of 60-70L/h and nutrient solution addition every 24-36 h.
8. The method according to claim 7, wherein the nutrient solution contains glucose, ammonium chloride, magnesium chloride, potassium chloride, yeast extract, and sodium dihydrogen phosphate.
9. The method according to any one of claims 1 to 8, wherein the conditions of the first and second mixing are the same, comprising stirring under magnetic stirring at a rotation speed of 200 to 300rpm for 15 to 60min and at a temperature of 30 to 35 ℃.
10. The method according to any one of claims 1 to 9, wherein the conditions of rest include a temperature of 30 to 35 ℃ for a time of 3 to 5 hours.
CN202310987108.3A 2023-08-07 2023-08-07 Method for determining the dispersibility of pharmaceutical agents on slime Pending CN119438324A (en)

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