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CN-122017087-A - Quality transmission quality control method for whole process of milk nuclear drink preparation

CN122017087ACN 122017087 ACN122017087 ACN 122017087ACN-122017087-A

Abstract

The invention discloses a quality transmission quality control method in the whole process of preparing milk nuclear drinks. The method comprises the steps of collecting milk nuclear drink concentrated solution, centrifugate and decoction samples, measuring seven physical parameters including pH, refractive index, dynamic viscosity, conductivity, total dissolved solids, solid content and density of the samples, constructing a physical fingerprint, measuring the contents of seven index components including gallic acid, chlorogenic acid, loganin, paeoniflorin, ferulic acid, chicoric acid and icariine by adopting an HPLC method, calculating the transfer rate of the index components in each process stage, establishing a chemical fingerprint, identifying a common peak, calculating the similarity, and analyzing the correlation between the physical parameters and the index components by using a thermal diagram. The multi-index evaluation mode of physical fingerprint spectrum-chemical fingerprint spectrum-multi-component content measurement constructed by the invention can systematically evaluate the influence of the traditional Chinese medicine preparation process on the whole quality, and provides scientific basis for the quality control of the traditional Chinese medicine production process.

Inventors

  • WU LEI
  • BIAN WEIHE
  • HU MENGMENG
  • TIAN LIYUAN
  • JIANG YIRAN

Assignees

  • 江苏省中医院

Dates

Publication Date
20260512
Application Date
20260402

Claims (10)

  1. 1. The quality transmission quality control method for the whole process of preparing the milk nuclear drink is characterized in that the milk nuclear drink is a traditional Chinese medicine composition prepared by decocting, concentrating, centrifuging and sterilizing the following components in parts by weight, namely, 1-5 parts of nutgrass galingale rhizome, 1-5 parts of corydalis tuber, 1-5 parts of szechuan lovage rhizome, 1-5 parts of rhizoma atractylodis, 1.5-10 parts of dandelion, 1-5 parts of tangerine seed, 1-5 parts of red paeony root, 1-5 parts of medicated leaven, 1-5 parts of dogwood, 1-5 parts of epimedium herb, 1-5 parts of turmeric and 1-5 parts of oriental waterplantain rhizome; The quality control method comprises the following steps: (1) Preparing test sample by collecting concentrated solution, centrifugated supernatant, and sterilized solution, and preparing concentrated solution test sample, centrifugated solution test sample, and sterilized solution test sample; (2) Preparing reference substances, namely respectively taking reference substances of gallic acid, chlorogenic acid, loganin, paeoniflorin, ferulic acid, chicoric acid and icariin, adding methanol for dissolving, then fixing the volume, preparing mother liquor for storage, precisely measuring the mother liquor of each reference substance, and uniformly mixing to prepare mixed reference substance solution; (3) Measuring physical fingerprints, namely measuring physical parameters of the concentrated solution to be tested, the centrifugate to be tested and the sterilizing solution to be tested in different batches, and respectively constructing the concentrated solution physical fingerprints, the centrifugate physical fingerprints and the sterilizing solution physical fingerprints, wherein the physical parameters comprise pH value, refractive index, dynamic viscosity, conductivity, total dissolved solid content, solid content and density; (4) Detecting the concentrated solution sample, the centrifugate sample and the sterilizing solution sample in different batches by adopting a high performance liquid chromatography to construct a concentrated solution chemical fingerprint, a centrifugate chemical fingerprint and a sterilizing solution chemical fingerprint; wherein, the high performance liquid chromatography detection conditions are as follows: the chromatographic column is a C18 chromatographic column, the mobile phase A is 0.1v/v% phosphoric acid aqueous solution, the mobile phase B is acetonitrile, gradient elution is carried out, the column temperature is 25 ℃, the detection wavelength is 254 nm, and the sample injection amount is 10 mu L; the gradient elution is carried out under the following conditions: the flow rate is 1.0 mL.min -1 ; (5) Measuring the content of chemical components, namely adopting the same chromatographic conditions as those in the step (4), injecting the test sample into a high performance liquid chromatograph, recording a chromatogram, and calculating the content of the chemical components in the test sample by an external standard method; wherein the chemical components are gallic acid, chlorogenic acid, loganin, paeoniflorin, ferulic acid, chicoric acid and icariin.
  2. 2. The method according to claim 1, wherein the decocting is performed for 2-3 times after adding water of 8-15 times the weight of the components in the formula for 1-2 hours, and the filtrate is combined by solid-liquid separation, preferably, the time of each decoction is 0.5-1 hour.
  3. 3. The method according to claim 1, wherein the concentration is carried out at a temperature of 90-100 ℃, and the concentration of the decocted filtrate is carried out to a density of 1.05-1.10 relative to water.
  4. 4. The method according to claim 1, wherein the centrifugation is to centrifuge the concentrated solution for 10-15 min at a rotational speed of 5000-6000 r.min -1 .
  5. 5. The method according to claim 1, wherein the sterilization is performed by sterilizing the centrifuged supernatant at 90-100 ℃ for 30-45 min.
  6. 6. The method according to claim 1, wherein the sample is prepared by sucking the concentrated solution, the supernatant after centrifugation and the sterilized solution 5 mL each, adding a solvent to a volume of 15: 15 mL, mixing, and filtering with a 0.22 μm microporous filter membrane, preferably wherein the solvent is methanol.
  7. 7. The method of claim 1, wherein the concentration of each control in the mixed control solution is 389.57 μg/mL gallic acid, 162.89 μg/mL chlorogenic acid, 526.33 μg/mL loganin, 1808.00 μg/mL paeoniflorin, 120.18 μg/mL ferulic acid, 517.39 μg/mL chicoric acid, 1790.00 μg/mL icariin, respectively.
  8. 8. The method of claim 1, wherein the physical fingerprint is constructed by measuring physical parameters of the concentrated solution sample, the centrifugate sample and the sterilizing solution sample in batches, normalizing the physical parameters, respectively establishing comparison physical fingerprints of the concentrated solution, the centrifugate and the sterilizing solution, and analyzing the similarity between each batch of samples and the comparison physical fingerprint by a correlation coefficient method, wherein the similarity is not lower than 0.9, and the batches are 15 batches.
  9. 9. The method according to claim 1, wherein the chemical fingerprint is constructed by processing chromatograms of the concentrated solution sample, the centrifugate sample and the sterilizing solution sample respectively by a traditional Chinese medicine chromatographic fingerprint similarity evaluation system to generate reference chemical fingerprints of concentrated solution, centrifugate and sterilizing solution respectively, wherein the similarity between each batch of sample fingerprints and the reference chemical fingerprint of the same process stage is not lower than 0.909, and the similarity between each batch of sample fingerprints and the reference chemical fingerprint of the concentrated solution is not lower than 0.988.
  10. 10. The method according to claim 1, wherein the chemical fingerprint comprises 7 characteristic peaks, namely No. 2 peak gallic acid, no. 7 peak chlorogenic acid, no.9 peak loganin, no.10 peak paeoniflorin, no. 11 peak ferulic acid, no. 13 peak chicoric acid and No. 17 peak icariin, and preferably, the relative retention time of each characteristic peak is respectively No. 2 peak gallic acid, 0.2786, no. 7 peak chlorogenic acid, 0.8717, no.10 peak paeoniflorin, no. 1.0993, no. 11 peak ferulic acid, no. 1.3000, no. 13 peak chicoric acid, no. 1.6169 and No. 17 peak icariin 2.3305.

Description

Quality transmission quality control method for whole process of milk nuclear drink preparation Technical Field The invention belongs to the field of traditional Chinese medicine quality control, and particularly relates to a quality transmission quality control method in the whole process of preparing a milk nuclear drink. Background The three quality attributes of the traditional Chinese medicine, namely stability, uniformity and controllability, are the precondition of guaranteeing the clinical safety and effectiveness of the traditional Chinese medicine, and are the fundamental requirements for responding to the public medication demands. From the feeding of medicinal materials to the filling of finished products, the tiny drift of temperature, time, pressure or solvent ratio of any unit operation such as extraction, concentration, purification, sterilization and the like can be amplified step by step in the transmission process, and finally, obvious differences of the content of effective components, physical properties and even safety indexes among batches are caused. Therefore, in the whole life cycle of modernization and industrialization of traditional Chinese medicine, how to lock the quality consistency into an insurmountable red line is always a core proposition facing three parties of supervision, production and scientific research. Only the dynamic relation between the technological parameters and the quality attributes is digitalized and modeled, and an online monitoring and feedback control mechanism is integrated, so that the predictable and controllable variation range between batches can be ensured. The breast nuclear drink is a clinical protocol prescription for treating hyperplasia of mammary glands in middle and high-grade hospitals in Jiangsu province for a long time, consists of twelve traditional Chinese medicines such as nutgrass galingale rhizome, rhizoma corydalis, szechuan lovage rhizome, swordlike atractylodes rhizome, dandelion, tangerine seed, red paeony root, medicated leaven, common macrocarpium fruit, epimedium herb, turmeric, oriental waterplantain rhizome and the like, has the effects of soothing liver, activating blood, softening hardness and dissipating stagnation, and can effectively relieve breast pain and dissipate breast nodules. Due to the difference of intermediate links in the preparation process of the milk nuclear drink, the compound preparation can possibly have fluctuation in the aspects of safety, stability and effectiveness. Therefore, establishing an effective quality control method becomes a primary task for promoting the research and clinical transformation of the compound preparation. Disclosure of Invention The invention aims to provide a quality control method for quality transmission in the whole process of preparing a milk nuclear drink, which aims at the technical defects that the existing quality control method for traditional Chinese medicine preparation can only evaluate terminal products and can not monitor quality transmission in the preparation process. In order to solve the technical problems, the invention adopts the following technical scheme: The quality transmission quality control method for the whole preparation process of the milk nuclear drink comprises the following components in parts by weight, namely, 1-5 parts of nutgrass galingale rhizome, 1-5 parts of corydalis tuber, 1-5 parts of szechuan lovage rhizome, 1-5 parts of rhizoma atractylodis, 1.5-10 parts of dandelion, 1-5 parts of tangerine seed, 1-5 parts of red paeony root, 1-5 parts of medicated leaven, 1-5 parts of dogwood, 1-5 parts of epimedium herb, 1-5 parts of turmeric and 1-5 parts of oriental waterplantain rhizome; The quality control method comprises the following steps: (1) Preparing test sample by collecting concentrated solution, centrifugated supernatant, and sterilized solution, and preparing concentrated solution test sample, centrifugated solution test sample, and sterilized solution test sample; (2) Preparing reference substances, namely respectively taking reference substances of gallic acid, chlorogenic acid, loganin, paeoniflorin, ferulic acid, chicoric acid and icariin, adding methanol for dissolving, then fixing the volume, preparing mother liquor for storage, precisely measuring the mother liquor of each reference substance, and uniformly mixing to prepare mixed reference substance solution; (3) Measuring physical fingerprints, namely measuring physical parameters of the concentrated solution to be tested, the centrifugate to be tested and the sterilizing solution to be tested in different batches, and respectively constructing the concentrated solution physical fingerprints, the centrifugate physical fingerprints and the sterilizing solution physical fingerprints, wherein the physical parameters comprise pH value, refractive index, dynamic viscosity, conductivity, total dissolved solid content, solid content and density; (4) Detecting the concentrated