CN114137104A - Process evaluation method of traditional Chinese medicine formula granules - Google Patents

Process evaluation method of traditional Chinese medicine formula granules Download PDF

Info

Publication number
CN114137104A
CN114137104A CN202111342741.4A CN202111342741A CN114137104A CN 114137104 A CN114137104 A CN 114137104A CN 202111342741 A CN202111342741 A CN 202111342741A CN 114137104 A CN114137104 A CN 114137104A
Authority
CN
China
Prior art keywords
cqa
characteristic
peak
spectrum
fingerprint
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
CN202111342741.4A
Other languages
Chinese (zh)
Other versions
CN114137104B (en
Inventor
张志强
沈建梅
杜微波
董晨虹
付静
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.)
Beijing Tcmages Pharmaceutical Co Ltd
Original Assignee
Beijing Tcmages Pharmaceutical Co Ltd
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 Beijing Tcmages Pharmaceutical Co Ltd filed Critical Beijing Tcmages Pharmaceutical Co Ltd
Priority to CN202111342741.4A priority Critical patent/CN114137104B/en
Publication of CN114137104A publication Critical patent/CN114137104A/en
Application granted granted Critical
Publication of CN114137104B publication Critical patent/CN114137104B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/86—Signal analysis
    • G01N30/8624—Detection of slopes or peaks; baseline correction
    • G01N30/8631—Peaks
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/86—Signal analysis
    • G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
    • G01N30/8686—Fingerprinting, e.g. without prior knowledge of the sample components
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography
    • 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
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P90/00—Enabling technologies with a potential contribution to greenhouse gas [GHG] emissions mitigation
    • Y02P90/30—Computing systems specially adapted for manufacturing

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Library & Information Science (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention provides a process evaluation method of traditional Chinese medicine formula granules, which adopts a key quality attribute similarity coefficient S of an evaluation indexcqaEvaluating a product generated in any step of the preparation process of the traditional Chinese medicine formula granules; said ScqaS including at least the peak area of the S peakcqaS of characteristic spectrum or fingerprint spectrumcqa(ii) a S using characteristic or fingerprint spectrumcqaThe process evaluation was carried out as follows: calculating S of the same characteristic peak of all productscqaThe ratio of the medium maximum value to the minimum value is selected, and S of the characteristic peak with the ratio being more than or equal to 2 is selectedcqaEvaluating and screening, and if the ratio of all characteristic peaks is less than 2, selecting S of all characteristic peakscqaEvaluating and screening; s for screening out the most numerous characteristic or fingerprint patterns with values closer to 1cqaThe corresponding process is carried out. The invention passes through ScqaThe value can be effectively evaluated for different production process stepsThe difference between the material basis of the obtained product and the material basis of the standard decoction ensures the consistency of the product and the standard decoction.

Description

Process evaluation method of traditional Chinese medicine formula granules
Technical Field
The invention relates to the field of traditional Chinese medicine preparation, and in particular relates to a process evaluation method of traditional Chinese medicine formula granules.
Background
The traditional Chinese medicine formula particle is prepared by feeding decoction pieces, extracting with water, concentrating, drying and granulating, maintains the material basis of water decoction extraction of the traditional Chinese medicine decoction, avoids the decoction link before clinical administration, and is an important practical mode for development of the traditional Chinese medicine decoction. The industry knows that the standard decoction is a standard reference substance for judging whether the traditional Chinese medicine formula granules are basically consistent with clinical decoction, and the material components of the standard decoction are closely related to the clinical curative effect. Generally, 3 parameters of cream yield, transfer rate (or content) of main active ingredients, fingerprint spectrum or characteristic spectrum are adopted in the traditional Chinese medicine formula granule standard to represent the quality of standard decoction; the research on the finished product process and the determination of the standard limit are based on the comparison of standard decoction, and the consistency of the granular preparation obtained by mass production and the traditional decoction in material composition is ensured. In all pharmaceutical studies, including process parameter determination, quality control methods and index selection, limitation control, etc., the study should be compared with "standard decoction".
In 4 months in 2021, the quality standards of 160 varieties of formula granules are released by the ministry of national formulary, and enterprises are encouraged to carry out standard research and recheck from standard decoction to production process and traditional Chinese medicine formula granule products according to technical requirements. However, only the characteristic spectrum standard and the content measurement result range are disclosed in the formula particle standard, while the quality difference of raw materials in the market is large at present, during the production verification of each enterprise, due to the difference of equipment and production conditions used in the large-scale production and the difference of the quality of raw material varieties, although the enterprise researches according to the technical requirements, the problem that the quality of finished products does not meet the published standard range can also exist, and a large amount of process parameter screening and optimization are needed to obtain the formula particles meeting the public standard. Therefore, how to research varieties and processes and how to obtain optimal process parameters more quickly are the key points and difficulties in the subsequent research of traditional Chinese medicine formula granules.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to overcome the problem that the optimal process parameters can not be obtained more quickly in the prior art, so that the formula particles prepared by the optimal process parameters meet the quality standard; therefore, the process evaluation method can effectively and quickly obtain the optimal process and ensure that the formula particles prepared by the optimal process meet the quality standard.
A process evaluation method of traditional Chinese medicine formula granules comprises the following steps:
key quality attribute similarity coefficient S adopting evaluation indexcqaEvaluating a product generated in any step of the preparation process of the traditional Chinese medicine formula granules; a key quality attribute similarity coefficient S of the evaluation indexcqaS including at least the peak area of the S peakcqaS of characteristic spectrum or fingerprint spectrumcqa；
S of the characteristic spectrum or fingerprint spectrumcqaThe acquisition process comprises the following steps: respectively obtaining characteristic spectrums or fingerprint spectrums of a standard decoction, a test sample and a reference sample, wherein the test sample comprises a product obtained in any step of the process of preparing the traditional Chinese medicine formula particles, and the reference sample is at least one component in the standard decoction; one component in a reference substance is adopted as an index component, a characteristic peak corresponding to the index component is marked in a characteristic spectrum or a fingerprint spectrum of a standard decoction and a test sample, the characteristic peak corresponding to the index component is adopted as an S peak, the relative peak area of each characteristic peak relative to the S peak displayed in the characteristic spectrum or the fingerprint spectrum is obtained, then the ratio of the relative peak areas of each corresponding characteristic peak in the test sample and the standard decoction is calculated, and the ratio is the S peak of the characteristic spectrum or the fingerprint spectrumcqa；
S of the peak area of the S peakcqaThe acquisition process comprises the following steps: calculating the ratio of the peak areas of the S peak in the sample and the standard decoction, wherein the ratio is the S of the peak area of the S peakcqa；
S using the peak area of the S peakcqaThe process evaluation was carried out as follows: selecting S within the range of 1 + -15%cqaThe process corresponding to the value;
s using characteristic or fingerprint spectrumcqaThe process evaluation was carried out as follows: meterCalculating the characteristic spectrum or fingerprint spectrum value S of the same characteristic peak of all productscqaSelecting the ratio of the maximum value to the minimum value, and selecting the characteristic spectrum of the characteristic peak or the S of the fingerprint spectrum with the ratio more than or equal to 2cqaEvaluating and screening, if the ratio of the maximum value to the minimum value of all characteristic peaks is less than 2, selecting the characteristic spectrum of all characteristic peaks or the S of the fingerprint spectrumcqaEvaluating and screening; s for screening out the most numerous characteristic or fingerprint patterns with values closer to 1cqaThe corresponding process is carried out.
If the corresponding screened processes are not less than two, the key quality attribute similarity coefficient S of the evaluation indexcqaAnd also comprises S of the cream yieldcqaOr/and S of index component content transfer ratecqa(ii) a Screening for S with a cream yield value closer to 1cqaOr/and S of index component content transfer ratecqaThe corresponding process is carried out;
s of the cream yieldcqaThe ratio of the ointment output of the test sample to the standard decoction output;
s of content transfer rate of the index componentcqaThe content transfer rate of the index component of the sample/the content transfer rate of the index component of the standard decoction.
S of the evaluation index when the product is an extracting solution in the preparation process of the traditional Chinese medicine formula granulescqaIncluding characteristic or fingerprint spectracqaAnd S of the peak area of the S peakcqa(ii) a Preferably, S is an evaluation indexcqaAnd also comprises S of the cream yieldcqaAnd/or S indicating the content transfer rate of the componentcqa；
Or S of the evaluation indexcqaS including cream yieldcqaAnd S indicating the content transfer rate of the componentcqa。
When the extractive solution is evaluated by the evaluation index, S of peak area of S peak is adoptedcqaScreening the process, and then adopting the S of the characteristic spectrum or the fingerprint spectrumcqaScreening the process; preferably, S of the paste yield is finally and simultaneously adoptedcqaAnd S indicating the content transfer rate of the componentcqaAnd (5) screening the process.
When the product is the extracting solution in the preparation process of the traditional Chinese medicine formula particles, if the index components are lost in the subsequent process steps, the S of the content transfer rate of the index components is selectedcqaThe extraction liquid is higher than 1 and lower than 1.5.
S of the evaluation index when the product is concentrated solution, dry powder or traditional Chinese medicine formula granulescqaIncluding characteristic or fingerprint spectracqaS peak area of S peakcqaS of index component content transfer ratecqa。
S using evaluation indexcqaThe procedure for evaluation was:
first, S of the peak area of the S peak is selectedcqaA process corresponding to a product within the range of 1 ± 15%; then adopting S of characteristic spectrum or fingerprint spectrum in the corresponding process of the productcqaAnd (3) performing evaluation screening, wherein the evaluation screening method comprises the following steps: calculating all characteristic spectrum or fingerprint spectrum values S of the same characteristic peakcqaSelecting the ratio of the maximum value to the minimum value, and selecting the characteristic spectrum of the characteristic peak or the S of the fingerprint spectrum with the ratio more than or equal to 2cqaScreening to screen out the S of the characteristic spectrum or fingerprint spectrum with the most quantity and the value closer to the numerical value 1cqaThe corresponding process is carried out;
if the ratio of the maximum value to the minimum value of all the characteristic peaks is less than 2, or the S of the characteristic spectrum or the fingerprint spectrum with the maximum quantity and the value closer to the numerical value 1 is selectedcqaWhen the corresponding processes are not less than two, the S of the content transfer rate of the index component is adoptedcqaScreening to obtain S with content transfer rate of index component closer to value 1cqaThe corresponding process is carried out.
S of a signature or fingerprint closer to 1cqaS of cream yieldcqaOr S indicating the content transfer rate of the componentcqaThe value of (A) is in the range of 1. + -. 30%.
S of a signature or fingerprint closer to 1cqaS of cream yieldcqaOr S indicating the content transfer rate of the componentcqaThe value of (A) is in the range of 1. + -. 15%.
The standard decoction is prepared from the raw materials in the same batch as the traditional Chinese medicine formula granules.
When the standard decoction is prepared from a plurality of batches of traditional Chinese medicine raw materials, the evaluation index of the standard decoction is obtained by the following steps: firstly, preparing the decoction by respectively adopting a plurality of batches of traditional Chinese medicine raw materials, detecting the evaluation index of each batch of decoction, and calculating the mean value of the detection result of each batch of decoction to obtain the evaluation index of the standard decoction.
The technical scheme of the invention has the following advantages:
1. the invention provides a process evaluation method of traditional Chinese medicine formula granules, wherein a new evaluation index-key quality attribute similarity coefficient S is providedcqaThe S ofcqaS including at least the peak area of the S peakcqaS of characteristic spectrum or fingerprint spectrumcqaAnd S of the evaluation indexcqaThe calculation method and rules of (3). The present invention is based on the S of the peak area of the above-mentioned S peakcqaValue and S of characteristic or fingerprintcqaThe value can effectively evaluate the difference between the material basis contained in the product prepared by different production process steps and the material basis contained in the standard decoction, so that the material basis contained in the product can be comprehensively evaluated, the amplitude of material change in the process of process research is reduced, the product and the material basis of the standard decoction are ensured to have higher consistency, the traditional Chinese medicine formula particles and the material basis of the standard decoction are finally promoted to have higher consistency, and the published standard range of the traditional Chinese medicine formula particles is met.
2. The invention further optimizes a process evaluation method of the traditional Chinese medicine formula granules, and also comprises S of cream yieldcqaS of index component content transfer ratecqaAt least one of; the invention is realized by carrying out S on the product of each process stepcqaThe evaluation of the invention can effectively assist in realizing the screening of the optimal process conditions of the whole process steps, and when the whole optimal process parameter conditions screened by the evaluation method are applied to mass production, the published standard range of the traditional Chinese medicine formula particles can be met through verification; thus, adoptThe evaluation method of the invention can screen out the process conditions suitable for the large-scale production of the traditional Chinese medicine formula granules more simply and conveniently, and effectively reduce the research cost of enterprise production verification.
3. The standard decoction prepared from the same batch of raw materials is used as a follow-up contrast, and the quality parameters of the standard decoction are used for individually guiding the process research, so that the quantity transmission in the process of the process research of each batch of formula granules can be ensured to meet the quality parameters of the standard decoction of the same batch, and the purpose reduction of the standard for meeting the published standard range of the corresponding traditional Chinese medicine formula granules and further the waste of traditional Chinese medicine resources caused by the purpose reduction of the standard during the research of the high-quality raw materials can be avoided.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is the S of the content transfer rate of saikosaponin a under different concentration temperature and time conditions in example 1 of the present inventioncqaA variation graph;
FIG. 2 is S of a characteristic map under different concentration temperature and time conditions in example 1 of the present inventioncqaA variation graph;
FIG. 3 is the S of the transfer rate of saikosaponin a content in each process step of mass production verification in example 2 of the present inventioncqaA variation graph;
FIG. 4 is S of citric acid content transfer rate under different concentration temperature and time conditions in example 3 of the present inventioncqaA variation graph;
FIG. 5 is S of a characteristic map under different concentration temperature and time conditions in example 3 of the present inventioncqaA variation graph;
FIG. 6 is S for verifying citric acid transfer rate in each process step in mass production in example 4 of the present inventioncqaAnd (5) a variation graph.
Detailed Description
Example 1
A process evaluation method of a traditional Chinese medicine formula granule is disclosed, wherein the traditional Chinese medicine formula granule in the embodiment is a bupleurum chinense formula granule. Specifically, the present embodiment uses the key quality attribute similarity coefficient ScqaSequentially evaluating products of bupleurum chinense decoction pieces obtained by different process steps, wherein the process evaluation comprises the following steps:
1. determining the preparation process of the standard decoction:
taking bupleurum chinense decoction pieces, placing the decoction pieces in a casserole, soaking for 30 minutes, adding water 9 times of the decoction pieces in the first decoction, boiling with strong fire (500w), decocting with slow fire for 20 minutes, filtering while hot, and rapidly cooling for later use; adding water with the amount 6 times that of decoction pieces into the second decoction, boiling with strong fire, decocting with slow fire (200w) for 15 minutes, filtering while hot, and rapidly cooling for later use; mixing filtrates, concentrating (below 50 deg.C) to obtain a concentrate with a ratio of 1:1 (relative density of 1.05-1.10 at 50 deg.C), and freeze drying.
2. The evaluation process of the process steps comprises:
2.1, obtaining standard decoction evaluation index parameters
2.1.1 detection method of evaluation indexes
2.1.1.1, detection method of cream yield:
taking one tenth of the total weight of the shaken standard decoction, placing in an evaporation dish with constant weight, evaporating in water bath, drying in an electrothermal blowing dry box at 105 deg.C for 5-6 hr, taking out, cooling in a drier for 30min, and weighing. And (3) measuring 2 parts in parallel for each batch, and calculating according to a formula that the cream yield is equal to the dry cream quantity/decoction piece quantity multiplied by 100 percent.
2.1.1.2, a detection method of the characteristic spectrum:
in chromatographic conditions and system applicability tests, octadecylsilane chemically bonded silica is used as a filler, the length of a column is 10cm, the inner diameter of the column is 2.1mm, and the particle size is 1.7 mu m; acetonitrile is taken as a mobile phase A, water is taken as a mobile phase B, and gradient elution is carried out according to the specification in the following table; the detection wavelength is 211nm and 250 nm; the column temperature is 35 ℃; the flow rate is 0.4 ml/min; the number of theoretical plates is not less than 10000 calculated according to the peak of saikosaponin a.
Gradient elution chart
Figure BDA0003352743580000051
Preparing a proper amount of sample for the test solution, grinding, taking about 1.0g, precisely weighing, placing in a conical flask with a plug, precisely adding 25ml of 50% ethanol containing 5% concentrated ammonia test solution, sealing the plug, weighing, ultrasonically treating (power 250W, frequency 40kHz) for 30 minutes, cooling, weighing again, supplementing the lost weight with 50% ethanol of 5% concentrated ammonia test solution, shaking uniformly, filtering, and taking the subsequent filtrate.
The measuring method comprises precisely sucking 3ul of reference solution and sample solution, respectively, injecting into liquid chromatograph, and measuring.
2.1.1.3, the detection method of the content of saikosaponin a comprises the following steps:
chromatographic conditions and System suitability test the detection wavelength was 211nm, the remainder being identical to the chromatographic conditions and System suitability test of 2.1.1.2.
Preparation of reference solution A proper amount of saikosaponin a reference is precisely weighed, and methanol is added to obtain solution containing 75 μ g per 1 ml.
Preparation of test solution the test solution was prepared as described for 2.1.1.2.
The determination method comprises precisely sucking 3 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and determining.
2.1.1.4, the content transfer rate of saikosaponin a is calculated according to the following calculation formula:
Figure BDA0003352743580000061
wherein, the content transfer rate is the transfer rate of saikosaponin a content, the decoction pieces with the same index component content are obtained by direct machine detection after being processed by the same processing method as the sample, and the sample is standard decoction or products of each link of the process.
2.1.2 obtaining evaluation index of standard decoction
The raw materials of 180209 one-time 043800-19 are used for process research, the preparation process of the standard decoction is adopted for preparation and detection, the paste yield of the standard decoction of the batch is 14.7%, the content transfer rate of the saikosaponin a is 15.2%, and the relative peak areas of the characteristic peaks of the characteristic spectrum are as follows: 0.27 (peak 1), 0.19 (peak 2), 1.00 (peak 3), 0.39 (peak 4), 0.06 (peak 5), 0.08 (peak 6), 2.95 (peak 7), 0.15 (peak 8), all meeting the standard decoction range.
2.2 evaluation of extraction Process parameters
The bupleurum chinense decoction pieces of 180209 one lot of 043800-19 are taken, each 100g is placed in a round bottom flask, water is added for soaking for 30 minutes, and the extraction times, the extraction time and the water addition amount which are described in the table 1 are adopted as the consideration factors for preparation, so that 9 groups of extracting solutions are obtained. Detecting 9 groups of extractive solutions with the same concentration as the standard decoction by the same detection method with saikosaponin a as index component to obtain S with peak area of S peak shown in Table 1cqaS of saikosaponin a content transfer ratecqaS of cream yieldcqaAnd S of the characteristic map shown in Table 2cqa. The paste yield in the invention is the dry extract yield, which is the dry extract amount/decoction piece input amount.
TABLE 1
Figure BDA0003352743580000071
TABLE 2
Figure BDA0003352743580000072
From the results of the characteristic maps, the S peaks of the experimental groups 3, 4, 6 and 8 were found to have ScqaWithin 1 +/-15%, relatively close to 1, and can be used as an alternative process group. And S due to the relative peak areas of the characteristic peaks 4, 5, 6, 7, 8cqaHas a maximum to minimum ratio of greater than 2, and therefore using peaks 4-8 as the primary evaluation peak allows screening of experimental group 4 closer to 1 than the other groups, i.e., the S of the feature mapcaqCharacteristic peak within 1 + -30%The extraction process of bupleurum chinense is determined as the best process corresponding to the experimental group 4 because the quantity of bupleurum chinense is the largest, namely: extracting for 2 times, each time for 0.5 hr, and each decocting with 10 times of water.
As another process evaluation method, S of saikosaponin a content transfer rate is adoptedcqaOr a cream yield ScqaWhen the transfer quantity value of the substance is controlled, the experimental groups 3 and 4 are closer to 1, but because the saikosaponin a has epoxy ether bond, the epoxy ether bond is easy to break and convert into the saikosaponin b1 under the high temperature condition, certain loss can occur in the subsequent concentration link, and certain loss can occur in the paste yield, so that S with the content transfer rate of the saikosaponin a is selectedcqaOr a cream yield ScqaThe slightly higher experimental group 4 as the optimal process can ensure the consistency of the sample in the subsequent concentration, drying, granulation and other links with the material basis of the standard decoction.
2.3 evaluation of concentration Process parameters
Taking the extract of the optimal extraction process, namely the extract obtained by the extraction process of the experimental group 4, uniformly mixing, equally dividing, placing in a centrifuge tube, performing water bath heat preservation at different temperatures, wherein the heat preservation temperature is set to be 50 ℃, 60 ℃, 70 ℃ and 80 ℃, collecting samples within different heat preservation time, and the sampling time is 3 hours, 6 hours, 9 hours, 12 hours and 24 hours from the heat preservation.
Detecting the concentrated solution obtained under different temperature and time conditions by the same detection method of the standard decoction to obtain S of saikosaponin a content transfer rate shown in Table 3cqaAnd S of saikosaponin a content transfer rate shown in figure 1cqaChange chart, and S of peak area of S peak shown in Table 4cqaS of characteristic mapcqaAnd a feature map S shown in FIG. 2cqaA variation diagram of (2).
TABLE 3
Figure BDA0003352743580000081
TABLE 4
Figure BDA0003352743580000082
The detection results show that: s of peak area of S peak at 50 ℃ to 70 ℃ for 24-hour concentration timecqaAnd S of the peak area of the S peak at a temperature of 80 ℃ for 6 to 12 hourscqaWithin 1 +/-15%, the concentration is relatively close to 1. And the relative peak areas S of the characteristic peaks 4, 5 and 7cqaHas a ratio of maximum to minimum of 2 or more, and therefore, by using the characteristic peaks 4, 5 and 7 as main evaluation peaks, it is possible to know the S of the characteristic spectrum at 50 ℃, 60 ℃ and 70 to 6 hourscaqValues close to 1 are more. Considering the efficiency of production and the acceptable degree of component loss, 70-6 h was determined as the optimum concentration temperature.
And S with saikosaponin a content transfer ratecaqThe result shows that the S of the content transfer rate of the saikosaponin a is increased within 24 hours of the concentration time at the temperature of 50 ℃ and 60 DEG CcaqThe numerical value is stable; s of saikosaponin a content transfer rate after 9 hours at 70 ℃ and 80 DEG CcaqWith a significantly downward trend. Therefore, 70-6 h can still be determined as the optimum concentration temperature, considering the efficiency of production and the acceptable degree of component loss.
2.4 evaluation of drying Pattern
The concentrated solution of the optimal concentration process is prepared by taking the concentrated solution density, the air inlet temperature and the auxiliary material amount which are shown in the table 5 as investigation factors, and 9 groups of dry products are obtained. Detecting the 9 groups of dried products by the same detection method as the standard decoction to obtain the content transfer rate S of saikosaponin a shown in Table 5cqaAnd S of the peak area of the S peak shown in Table 6cqaAnd S of the feature mapcqa。
TABLE 5
Figure BDA0003352743580000091
TABLE 6
Figure BDA0003352743580000092
Figure BDA0003352743580000101
As is clear from the results in the tables, the S peaks of the experimental groups 5, 6 and 8 showed ScqaWithin 1 +/-15%, is relatively close to 1, and S of other characteristic peaks of the characteristic spectrumcqaRelatively close to 1, i.e. S of the feature mapcaqS of characteristic maps within 1 plus or minus 30 percentcaqThe number of (2) is the same. Thus by the S of the feature mapcaqThe experimental groups 5, 6 and 8 can be screened to be alternative processes. Further using S of saikosaponin a content transfer ratecqaThe experimental phenomena are preferably combined, and it is known that: s of saikosaponin a content transfer rate of experimental group 5cqaThe values are closer to 1, indicating that the material basis is closer to that of the standard decoction, thus determining the spray drying process as: the density of the feed liquid is 1.10, 17 percent of auxiliary materials, and the air inlet temperature is 170 ℃.
Example 2
The present example is used to verify the process condition parameters obtained in the mass production verification example 1, and specifically includes the following steps:
three batches of bupleurum chinense decoction pieces are respectively numbered as 1, 2 and 3, production verification is carried out according to the process selected in the embodiment 1, samples prepared in each process link are collected, and detection is carried out according to the method in the embodiment 1. As the auxiliary materials are added in the production process of the bupleurum chinense formula particle, the cream yield can not directly reflect the quantity value transmission condition of the substances, so the content transfer rate of the saikosaponin a and the S of the characteristic spectrum are usedcqaAnd analyzing the transmission condition of the quality index of each link. Wherein the content transfer rate of saikosaponin a is ScqaAs shown in Table 7 and FIG. 3, S in the peak area of the S peakcqaAnd S of each characteristic peak of the characteristic mapcqaAs shown in table 8.
TABLE 7
Figure BDA0003352743580000102
The results of the tests in Table 7 and FIG. 3 show that: transfer rate S of saikosaponin a contentcqaFrom the standard decoction to the end of the preparation process of the bupleurum chinense formula particles, the transfer rate is reduced by about 10 percent, and the loss is less.
TABLE 8
Figure BDA0003352743580000103
Figure BDA0003352743580000111
The results of the tests in Table 8 show that: producing characteristic spectrum S peak of each link and S of the rest characteristic peakscqaThe transmission is more stable.
In conclusion: taking standard decoction as reference, and taking the ointment yield, index component content (or transfer rate), and S of characteristic mapcqaIn order to examine indexes, the selected process parameters are reasonable, the quantity value transmission is stable, and the quality of the obtained product can be consistent with that of the standard decoction.
Example 3
A process evaluation method of traditional Chinese medicine formula granules is provided, wherein the traditional Chinese medicine formula granules in the embodiment are dark plum formula granules. Specifically, the present embodiment uses the key quality attribute similarity coefficient ScqaSequentially evaluating products of the dark plum slices obtained in different process steps, wherein the process evaluation process comprises the following steps:
1. determining the preparation process of the standard decoction:
placing 180627 and 611300-13 batches of fructus mume decoction pieces in a casserole, soaking for 30 minutes, adding 6 times of water for decoction pieces in one decoction, boiling with strong fire (500w), decocting with slow fire for 30 minutes, filtering while hot, and rapidly cooling for later use; adding water with the amount 4 times that of decoction pieces into the second decoction, boiling with strong fire, decocting with slow fire (200w) for 20 minutes, filtering while hot, and rapidly cooling for later use; mixing filtrates, concentrating (below 50 deg.C) to obtain a concentrate with a ratio of 1:1 (relative density of 1.05-1.10 at 50 deg.C), and freeze drying.
2. The evaluation process of the process steps comprises:
2.1, obtaining standard decoction evaluation index parameters
2.1.1 detection method of evaluation indexes
2.1.1.1, detection method of cream yield:
taking one tenth of the total weight of the shaken standard decoction, placing in an evaporation dish with constant weight, evaporating in water bath, drying in an electrothermal blowing dry box at 105 deg.C for 5-6 hr, taking out, cooling in a drier for 30min, and weighing. And (3) measuring 2 parts in parallel for each batch, and calculating according to a formula that the cream yield is equal to the dry cream quantity/decoction piece quantity multiplied by 100 percent.
2.1.1.2, the citric acid content detection method comprises the following steps:
measuring by high performance liquid chromatography (China pharmacopoeia 2020 edition four-part general regulation 0512).
Chromatographic conditions and system applicability test with octadecylsilane chemically bonded silica as filler (column length of 10cm, inner diameter of 2.1mm, particle diameter of 1.8 μm); using methanol as mobile phase A and 0.2% phosphoric acid as mobile phase B, and performing gradient elution according to the specification in the following table; the detection wavelength is 210 nm; the column temperature is 30 ℃; the flow rates are shown in the gradient elution table. The number of theoretical plates is not less than 3000 calculated according to citric acid peak.
Gradient elution chart
Figure BDA0003352743580000121
Preparation of control solution A proper amount of citric acid control was weighed precisely, and 10% methanol was added to make a solution containing 4.0mg per 1ml as a control solution.
Preparing a test solution by taking a proper amount of the product, grinding, taking about 0.2g, precisely weighing, placing in an erlenmeyer flask, precisely adding 25ml of water, sealing, weighing, carrying out ultrasonic treatment (power 250W and frequency 40kHz) for 30 minutes, cooling, weighing again, supplementing the weight lost by water, shaking up, filtering, and taking a subsequent filtrate.
The determination method comprises precisely sucking 2 μ l of each of the reference solution and the sample solution, injecting into an ultra high performance liquid chromatograph, and determining.
2.1.1.3, and a calculation formula of citric acid content transfer rate:
Figure BDA0003352743580000122
wherein, the sample is standard decoction or products of each link of the process, and the decoction pieces with the same index component content are obtained by direct machine detection after being processed by the same processing method as the sample.
2.1.1.4, a detection method of the characteristic spectrum comprises the following steps:
chromatographic conditions and System suitability test the same 2.1.1.2 chromatographic conditions and System suitability test.
Control reference solutions were prepared in the same manner as 2.1.1.2.
Preparation of test solution the test solution was prepared as described for 2.1.1.2.
The determination method comprises precisely sucking reference substance solution and sample solution of reference substance 2 μ l each, injecting into ultra high performance liquid chromatograph, and determining.
6 characteristic peaks are presented in the characteristic map of the test sample, wherein the retention time of the peak 2 is consistent with that of a reference substance, the peak 2 is taken as an S peak, the relative retention time of the characteristic peaks 1-6 is calculated, and the relative retention time is within +/-10% of a specified value. The predetermined values were 0.52 (peak 1), 1.00 (peak 2), 2.00 (peak 3), 2.99 (peak 4), 4.05 (peak 5), and 4.20 (peak 6).
2.1.2 obtaining evaluation index of standard decoction
The technical research is carried out on the batch of the dark plum decoction pieces 180627 and 611300-13, the preparation technology of the standard decoction pieces is adopted for preparation and detection, the paste yield of the batch of the standard decoction pieces is 21.1 percent, the citric acid content is 57.4 percent, the citric acid content transfer rate is 75.7 percent, and the relative peak areas of all characteristic peaks of the characteristic spectrum are as follows: 0.141 (peak 1), 1.00 (peak 2), 0.037 (peak 3), 0.034 (peak 4), 0.029 (peak 5), 0.033 (peak 6), all in accordance with the standard decoction range.
2.2 evaluation of extraction Process parameters
The dark plum pieces of 180627 and 611300-13 batches are taken, 100g of each piece is placed in a round-bottom flask, water is added for soaking for 30 minutes, and extraction times, extraction time and water addition amount which are described in the table 9 are taken as consideration factors for preparation, so that 9 groups of extracting solutions are obtained. Detecting 9 groups of extractive solutions with the same concentration as the standard decoction by the same detection method with citric acid as index component to obtain citric acid content transfer rate S shown in Table 9cqaS of cream yieldcqaAnd S of the peak area of the S peak shown in Table 10cqaAnd S of the feature mapcqa。
TABLE 9
Figure BDA0003352743580000131
Watch 10
Figure BDA0003352743580000132
S in peak area of S peakcqaAnd a characteristic map ScqaAnalysis, S of peak area of S peak of each experimental groupcqaAnd a characteristic map ScqaThe results are all closer to 1, i.e. the S of the peak areacqaAll within 1 +/-15 percent, and S of a characteristic mapcaqAll within 1 + -30%, and therefore, the S is the peak area of the S peakcqaAnd S of the feature mapcqaTo obtain: the above 9 sets may be used as alternative processes. Further, the S content can be transferred at a creaming rate or a citric acid contentcqaFurther screening is carried out, wherein the S of the citric acid content transfer rate of the experimental groups 3 and 4cqaWithin 1 +/-30 percent, the paste yield is ScqaThe content of citric acid in the experimental groups 3 and 4 is within 1 plus or minus 30 percent, so the transfer rate or the cream yield S of the citric acid in the experimental groups 3 and 4 can be screenedcqaCloser to 1. But considering that certain loss can occur in the subsequent concentration and drying process, the cream yield or citric acid content transfer rate S is selectedcqa Experiment group 3, slightly higher, to ensure the consistency of the sample in the subsequent concentration, drying, granulation and other links with the standard decoction material basis.
Therefore, the extraction process of the dark plum can be determined to be the process corresponding to the experimental group 3, namely: extracting for 1 time, 1.5 hr each time, and adding 12 times of water for each decoction.
2.3 evaluation of concentration Process parameters
Taking the extract of the optimal extraction process, mixing uniformly, dividing equally, placing in a centrifuge tube, performing water bath heat preservation at different temperatures, setting the heat preservation temperature at 50 ℃, 60 ℃, 70 ℃ and 80 ℃, and collecting samples within different heat preservation time, wherein the sampling time is 2h, 4h, 6h, 8h, 12h and 24h from the beginning of heat preservation.
Detecting the concentrated solution obtained under different temperature and time conditions by the same detection method of the standard decoction to obtain citric acid content transfer rate S shown in Table 11cqaAnd S of citric acid content transfer rate shown in FIG. 4cqaChange chart, and S of peak area of S peak shown in Table 12cqaAnd S of the feature mapcqaAnd a feature map S shown in FIG. 5cqaA variation diagram of (2).
TABLE 11
Figure BDA0003352743580000141
TABLE 12
Figure BDA0003352743580000142
Figure BDA0003352743580000151
The detection results show that: s of peak area of S peak at different concentration temperaturescqaAnd S of the characteristic mapcaqAre all relatively close to 1, i.e. the S of the peak areacqaAll within 1 +/-15 percent, and S of a characteristic mapcaqThe concentration is within 1 +/-30%, which shows that the components are relatively stable and do not have the transformation phenomenon, and the 80 ℃ is determined as the optimal concentration temperature in consideration of the later production efficiency.
And S of citric acid content transfer rate at different concentration temperaturescqaThe values are all relatively close to 1, and 80 ℃ is determined as the optimal concentration temperature by considering the later production efficiency.
2.4 evaluation of drying Pattern
The concentrated solution of the optimum concentration process was prepared using the drying method, the auxiliary material ratio and the drying temperature described in table 13 as the investigation factors to obtain 10 groups of dried products. Detecting 10 groups of dried products by the same detection method as the above standard decoction to obtain citric acid content transfer rate S shown in Table 13cqaAnd S of the peak area of the S peak shown in Table 14cqaAnd S of the feature mapcqa。
Watch 13
Figure BDA0003352743580000152
Figure BDA0003352743580000161
TABLE 14
Figure BDA0003352743580000162
The detection results show that: s of the S peaks of the experimental groups 1, 3, 4, 5, 6, 7, 8cqaS relatively close to 1, i.e. peak areacqaAll within 1 +/-15%, and the S of characteristic spectrum in peak 4-6cqaIs greater than 2, and therefore the screening is performed with peaks 4, 5, 6 as the key assessment peaks, wherein the S of the characteristic profiles of the experimental groups 1, 3, 7, 8cqaThe amount is more within 1 +/-30 percent, so that the screened experimental groups 1, 3, 7 and 8 are closer to 1, and the S with the citric acid content transfer rate is usedcqaAnalysis was performed in which only S of citric acid content transfer rate in experiment group 8 was usedcqaThe numerical value is within 1 +/-15%, and the following results are obtained: experimental group 8 was closer to 1, thus determining the drying process as: the drying is carried out in a belt type,the auxiliary material is 15% dextrin, and the drying is carried out at 80 ℃.
Example 4
The present embodiment is used for verifying the process condition parameters obtained in the mass production verification embodiment 3, and specifically includes the following steps:
three batches of dark plum slices are respectively numbered as 1, 2 and 3, production verification is carried out according to the process selected in the embodiment 3, samples prepared in all process links are collected, and detection is carried out according to the method in the embodiment 3. Because the auxiliary materials are added in the production process of the formula particles, the cream yield can not directly reflect the quantity value transmission condition of the substances, and therefore, the citric acid content transfer rate and the S of the characteristic spectrum are usedcqaAnd analyzing the transmission condition of the quality index of each link. Wherein the citric acid content transfer rate is ScqaAs shown in Table 15 and FIG. 6, S is the peak area of the S peakcqaAnd S of each characteristic peak of the characteristic mapcqaAs shown in table 16.
Watch 15
Figure BDA0003352743580000163
Figure BDA0003352743580000171
As can be seen from the results of the above table 15 and fig. 6: citric acid content transfer rate ScqaThe transfer rate is reduced by about 15% from standard decoction to the end of the preparation process of the dark plum formula granules, and the sample amount is probably larger than the process research in production verification, so the drying link time is longer, and the citric acid content is reduced.
TABLE 16
Figure BDA0003352743580000172
The results of the measurements in Table 16 show that: production of S of peak area of S peak of each linkcqaAnd S of each characteristic peak in the characteristic mapcqaThe transmission is more stable.
In conclusion: taking standard decoction as reference, and taking the ointment yield, index component content (or transfer rate), and S of characteristic mapcqaIn order to examine indexes, the selected process parameters are reasonable, the quantity value transmission is stable, and the quality of the obtained product can be consistent with that of the standard decoction.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims (10)

1. A process evaluation method of traditional Chinese medicine formula granules is characterized in that a key quality attribute similarity coefficient S of evaluation indexes is adoptedcqaEvaluating a product generated in any step of the preparation process of the traditional Chinese medicine formula granules; a key quality attribute similarity coefficient S of the evaluation indexcqaS including at least the peak area of the S peakcqaS of characteristic spectrum or fingerprint spectrumcqa；
S of the characteristic spectrum or fingerprint spectrumcqaThe acquisition process comprises the following steps: respectively obtaining characteristic spectrums or fingerprint spectrums of a standard decoction, a test sample and a reference sample, wherein the test sample comprises a product obtained in any step of the process of preparing the traditional Chinese medicine formula particles, and the reference sample is at least one component in the standard decoction; one component in a reference substance is adopted as an index component, a characteristic peak corresponding to the index component is marked in a characteristic spectrum or a fingerprint spectrum of a standard decoction and a test sample, the characteristic peak corresponding to the index component is adopted as an S peak, the relative peak area of each characteristic peak relative to the S peak displayed in the characteristic spectrum or the fingerprint spectrum is obtained, then the ratio of the relative peak areas of each corresponding characteristic peak in the test sample and the standard decoction is calculated, and the ratio is the S peak of the characteristic spectrum or the fingerprint spectrumcqa；
S of the peak area of the S peakcqaIs obtained by: calculating the ratio of the peak areas of the S peak in the sample and the standard decoction, wherein the ratio is the S of the peak area of the S peakcqa；
S using the peak area of the S peakcqaThe process evaluation was carried out as follows: selecting S within the range of 1 + -15%cqaThe process corresponding to the value;
s using characteristic or fingerprint spectrumcqaThe process evaluation was carried out as follows: calculating the characteristic spectrum or fingerprint spectrum value S of the same characteristic peak of all productscqaSelecting the ratio of the maximum value to the minimum value, and selecting the characteristic spectrum of the characteristic peak or the S of the fingerprint spectrum with the ratio more than or equal to 2cqaEvaluating and screening, if the ratio of the maximum value to the minimum value of all characteristic peaks is less than 2, selecting the characteristic spectrum of all characteristic peaks or the S of the fingerprint spectrumcqaEvaluating and screening; s for screening out the most numerous characteristic or fingerprint patterns with values closer to 1cqaThe corresponding process is carried out.
2. The method for evaluating the process of a Chinese medicinal granule according to claim 1,
if the corresponding screened processes are not less than two, the key quality attribute similarity coefficient S of the evaluation indexcqaAnd also comprises S of the cream yieldcqaOr/and S of index component content transfer ratecqa(ii) a Screening for S with a cream yield value closer to 1cqaOr/and S of index component content transfer ratecqaThe corresponding process is carried out;
s of the cream yieldcqaThe ratio of the ointment output of the test sample to the standard decoction output;
s of content transfer rate of the index componentcqaThe content transfer rate of the index component of the sample/the content transfer rate of the index component of the standard decoction.
3. The method for evaluating a process of preparing a Chinese medicinal granule according to claim 2, wherein the product is an extract in a process of preparing a Chinese medicinal granule, the evaluation index is ScqaInvolving characteristic or finger-printScqaAnd S of the peak area of the S peakcqa(ii) a Preferably, S is an evaluation indexcqaAnd also comprises S of the cream yieldcqaAnd/or S indicating the content transfer rate of the componentcqa(ii) a Or S of the evaluation indexcqaS including cream yieldcqaAnd S indicating the content transfer rate of the componentcqa。
4. The method of claim 3, wherein the evaluation index is used to evaluate the extractive solution by first using the peak area of ScqaScreening the process, and then adopting the S of the characteristic spectrum or the fingerprint spectrumcqaScreening the process; preferably, S of the paste yield is finally and simultaneously adoptedcqaAnd S indicating the content transfer rate of the componentcqaAnd (5) screening the process.
5. The method for evaluating a process of a Chinese medicinal granule according to any one of claims 2 to 4, wherein said evaluation index S is S when said product is a concentrated solution, a dried powder or a Chinese medicinal granulecqaIncluding characteristic or fingerprint spectracqaS peak area of S peakcqaS of index component content transfer ratecqa。
6. The method for evaluating the process of a Chinese medicinal granule according to claim 5, wherein S is used as an evaluation indexcqaThe procedure for evaluation was:
first, S of the peak area of the S peak is selectedcqaA process corresponding to a product within the range of 1 ± 15%; then adopting S of characteristic spectrum or fingerprint spectrum in the corresponding process of the productcqaAnd (3) performing evaluation screening, wherein the evaluation screening method comprises the following steps: calculating all characteristic spectrum or fingerprint spectrum values S of the same characteristic peakcqaSelecting the ratio of the maximum value to the minimum value, and selecting the characteristic spectrum of the characteristic peak or the S of the fingerprint spectrum with the ratio more than or equal to 2cqaEvaluating and screening, and if the ratio of the maximum value to the minimum value of all characteristic peaks is less than 2, selecting all characteristic peaksCharacteristic spectrum of characteristic peak or S of fingerprint spectrumcqaEvaluating and screening; s for screening out the most numerous characteristic or fingerprint patterns with values closer to 1cqaThe corresponding process is carried out;
if the corresponding processes are not less than two, then adopting S of index component content transfer ratecqaScreening to obtain S with content transfer rate of index component closer to value 1cqaThe corresponding process is carried out.
7. The method for evaluating a process of a Chinese medicinal granule according to any one of claims 2 to 6, wherein S of the characteristic spectrum or fingerprint closer to 1cqaS of cream yieldcqaOr S indicating the content transfer rate of the componentcqaThe value of (A) is in the range of 1. + -. 30%.
8. The method of claim 7, wherein the characteristic spectrum or fingerprint S of the particle is closer to 1cqaS of cream yieldcqaOr S indicating the content transfer rate of the componentcqaThe value of (A) is in the range of 1. + -. 15%.
9. The method for evaluating a process of a Chinese medicinal granule according to any one of claims 1 to 8, wherein the standard decoction is prepared from the same lot of raw materials as the Chinese medicinal granule.
10. The method for evaluating a process of a Chinese medicinal granule according to any one of claims 1 to 8, wherein when the standard decoction is prepared from a plurality of batches of Chinese medicinal materials, the evaluation index of the standard decoction is obtained by: firstly, preparing the decoction by respectively adopting a plurality of batches of traditional Chinese medicine raw materials, detecting the evaluation index of each batch of decoction, and calculating the mean value of the detection result of each batch of decoction to obtain the evaluation index of the standard decoction.
CN202111342741.4A 2021-11-12 2021-11-12 Process evaluation method of traditional Chinese medicine formula particles Active CN114137104B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111342741.4A CN114137104B (en) 2021-11-12 2021-11-12 Process evaluation method of traditional Chinese medicine formula particles

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111342741.4A CN114137104B (en) 2021-11-12 2021-11-12 Process evaluation method of traditional Chinese medicine formula particles

Publications (2)

Publication Number Publication Date
CN114137104A true CN114137104A (en) 2022-03-04
CN114137104B CN114137104B (en) 2023-08-22

Family

ID=80393865

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111342741.4A Active CN114137104B (en) 2021-11-12 2021-11-12 Process evaluation method of traditional Chinese medicine formula particles

Country Status (1)

Country Link
CN (1) CN114137104B (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107271589A (en) * 2017-01-19 2017-10-20 安徽九洲方圆制药有限公司 A kind of semen armeniacae amarae granule and its preparation and method of quality control
CN109946394A (en) * 2019-03-08 2019-06-28 劲牌生物医药有限公司 The quality determining method of the HPLC characteristic spectrum and its construction method of the coptis and application, coptis
CN112098568A (en) * 2019-06-17 2020-12-18 国药集团同济堂（贵州）制药有限公司 Preparation method and quality detection method of dark plum extract
CN112881540A (en) * 2019-11-29 2021-06-01 北京康仁堂药业有限公司 Method for detecting bupleurum chinense and vinegar bupleurum chinense formula granules

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107271589A (en) * 2017-01-19 2017-10-20 安徽九洲方圆制药有限公司 A kind of semen armeniacae amarae granule and its preparation and method of quality control
CN109946394A (en) * 2019-03-08 2019-06-28 劲牌生物医药有限公司 The quality determining method of the HPLC characteristic spectrum and its construction method of the coptis and application, coptis
CN112098568A (en) * 2019-06-17 2020-12-18 国药集团同济堂（贵州）制药有限公司 Preparation method and quality detection method of dark plum extract
CN112881540A (en) * 2019-11-29 2021-06-01 北京康仁堂药业有限公司 Method for detecting bupleurum chinense and vinegar bupleurum chinense formula granules

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
何根祥等: "柴 胡标准汤剂的制备及其 质量评价研究" *
孙福仁等: "柴胡标准汤剂两种成分测定方法研究" *
李昕等: "不同加工方法乌梅UPLC特征图谱及模式识别研究" *
殷文俊 等: "基于特征图谱 和量值传递关系评价荆 芥配方颗粒的关键生产工艺" *
许金国 等: "经典名方当归 四逆汤物质基准量值传递分析" *

Also Published As

Publication number Publication date
CN114137104B (en) 2023-08-22

Similar Documents

Publication Publication Date Title
CN108355047B (en) Preparation process of lily and rehmannia decoction solid preparation
CN107854312A (en) A kind of preparation technology of Chinese medicine preparation
CN113759020B (en) Preparation process and quality control method of channel warming soup
CN108362788A (en) A kind of steamed sealwort Quality Detection analysis method
CN112763617A (en) Method for constructing characteristic maps of standard decoctions of semen Persicae preparata in different producing areas and application thereof
CN113759017A (en) Preparation process and evaluation method of angelica sinensis Liuhuang decoction
CN108355041A (en) A kind of preparation process of Gualou Xiebai Banxia Tang solid pharmaceutical preparation
CN106074695A (en) A kind of DANSHEN KELI and Chinese medicine preparation thereof
CN113777183B (en) Glossy privet fruit medicinal material and its processed product characteristic spectrum construction method and multi-index component content detection method
CN110514761B (en) Method for constructing HPLC (high Performance liquid chromatography) characteristic spectrum of traditional Chinese medicine preparation for moistening lung and relieving cough
CN110007031B (en) Fingerprint detection method of glossy privet fruit roasted with liquorice juice
CN108524883B (en) Preparation process of Zhenwu soup solid preparation
CN114137104A (en) Process evaluation method of traditional Chinese medicine formula granules
CN115267008B (en) Construction method of characteristic spectrum and comparison spectrum of bamboo juice pinellia ternate and distinguishing method of different processed products of pinellia ternate
CN113759018B (en) Evaluation method of evodia rutaecarpa decoction preparation process
CN113759006B (en) Quality control method of radix curcumae longae formula granules
CN106018647B (en) A kind of method for setting up sunflower disk HPLC standard finger-prints
CN113759007B (en) Quality control method of curcuma kwangsiensis
CN114113434B (en) Process evaluation method of traditional Chinese medicine formula granules containing volatile oil
CN106540233A (en) A kind of preparation method of tangerine peel bamboo shavings granule
CN114113433A (en) Preparation process and evaluation method of flos farfarae formula granules
CN106074743B (en) A kind of detection method of moutan bark particle
CN101698079A (en) Quality test method of Wenweishu granules
CN101524410A (en) Preparation method of corydalis tuber decoction pieces
CN106109696B (en) A kind of detection method of radix scrophulariae particle

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