CN112603969A - Large-scale controllable fermentation method of Massa Medicata Fermentata with ten thousand-level cleanliness - Google Patents

Large-scale controllable fermentation method of Massa Medicata Fermentata with ten thousand-level cleanliness Download PDF

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CN112603969A
CN112603969A CN202011506340.3A CN202011506340A CN112603969A CN 112603969 A CN112603969 A CN 112603969A CN 202011506340 A CN202011506340 A CN 202011506340A CN 112603969 A CN112603969 A CN 112603969A
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fermentation
cleanliness
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massa medicata
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林飞武
杨利博
武玉翠
田春雨
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Hebei Lin Yitang Pharmaceutical Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
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    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
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    • A61K36/73Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract

The invention discloses a scale controllable fermentation method of Massa Medicata Fermentata with ten thousand grades cleanliness, which comprises the steps of crushing sweet wormwood, red knotweed, xanthium sibiricum, red bean, bitter almond, wheat bran and flour, adding water, stirring and making leaven; then placing the obtained yeast material in a ten thousand-level fermentation workshop with cleanliness, and controlling the fermentation conditions as follows: the air cleanliness is more than 1 ten thousand grade, the pressure of a fermentation workshop is kept more than 10Pa higher than that of an unclean area, the fermentation temperature is 25-35 ℃, and the humidity of the fermentation environment is 70-90%; and (4) after fermentation, ventilating and drying to constant weight to obtain the finished product of the medicated leaven. The invention makes the fermentation of the medicated leaven more sufficient, the content of effective fingerprint components in the product is higher than that of the traditional fermentation mode, the fermentation time is short, the fermentation efficiency is high, the harmful mixed bacteria pollution in the medicated leaven processing process is reduced, the medicated leaven fermentation process is standardized, unified and safe, and is not limited by natural conditions, and the continuous production all the year around is realized.

Description

Large-scale controllable fermentation method of Massa Medicata Fermentata with ten thousand-level cleanliness
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a cleanliness-level large-scale controllable fermentation method of medicated leaven.
Background
Medicated leaven, also called medicated leaven and medicated leaven, is a traditional Chinese medicinal leaven prepared by mixing Polygonum hydropiper, Artemisia annua, Xanthium sibiricum, semen Phaseoli, Almond, wheat bran and flour according to a certain proportion and then naturally fermenting. Liushen qu is sweet and pungent in flavor and warm in nature, enters spleen and stomach channels, is a most widely applied starter in the traditional starter, has the effects of strengthening spleen and stomach, helping digestion and regulating middle energizer and relieving exterior syndrome, and is mainly used for treating diseases such as diet stagnation, chest fullness and abdominal distension, vomiting and diarrhea, postpartum blood stasis and abdominal pain, children abdominal distension and mass and the like in clinic.
The six medicated leaven market has a large annual demand, but the products produced in batch are few, most of the products are produced and processed by individual pharmaceutical manufacturers, the production process is extremely irregular, and the labor and materials are stolen, so that the quality difference of the six medicated leaven is obvious, and the safety and the effect of clinical medication are seriously influenced. The traditional medicated leaven processing method mainly utilizes a manual method for natural fermentation and executes respective local processing standards. Because of the limitation of natural conditions such as temperature, humidity and the like, the fermentation conditions are extremely unstable, the fermentation efficiency is low, and continuous production all year round cannot be realized. In addition, the putrefactive microorganisms are excessively increased due to natural fermentation, and if aspergillus flavus toxin exceeds the standard due to the increase of aspergillus flavus, the medication safety is seriously influenced. The local processing mode causes uneven quality of medicated leaven finished products, objective evaluation of the quality of medicated leaven is difficult to perform, the quality of medicated leaven can only be simply evaluated from the aspects of appearance, smell, microscopic examination and the like of the medicated leaven at present, and a quantitative quality evaluation method is lacked.
Disclosure of Invention
The invention aims to provide a massa medicata fermentata large-scale controllable fermentation method with ten thousand grades of cleanliness, which is used for reducing the mixed bacteria pollution in the massa medicata fermentata processing process, standardizing, unifying and safening the massa medicata fermentata fermentation process, is not limited by natural conditions, and realizes the annual continuous production.
Aiming at the purposes, the technical scheme adopted by the invention comprises the following steps:
step 1: pulverizing herba Artemisiae Annuae, herba Polygoni Hydropiperis, herba Xanthii, semen Phaseoli, semen Armeniacae amarum, testa Tritici, and flour, adding water, stirring, and making starter.
Step 2: placing the yeast material obtained in the step 1 in a fermentation workshop with ten thousand grades of cleanliness, and controlling the fermentation conditions as follows: the air cleanliness is more than 1 ten thousand grade, the pressure of a fermentation workshop is kept more than 10Pa higher than that of an unclean area, the fermentation temperature is 25-35 ℃, the humidity of the fermentation environment is 70-90%, and the fermentation time is 48-72 hours.
And step 3: and (3) ventilating and drying the fermented medicated leaven at 40-60 ℃ to constant weight.
In the step 1, the raw materials are mixed according to the following mass portions: 0.2-2 parts of sweet wormwood, 0.2-2 parts of polygonum hydropiper, 0.2-2 parts of xanthium sibiricum, 2-5 parts of phaseolus calcaratus, 2-5 parts of bitter almond, 20-50 parts of wheat bran and 20-50 parts of flour, and the components are ground and sieved by a sieve of 40-60 meshes.
In the step 1, the water content in the koji material for koji making is preferably 35 wt.% to 45 wt.%.
In the step 2, the cleanliness of the fermentation workshop with ten thousand grades of cleanliness is controlled by an air self-cleaning device, the temperature is controlled by a constant-temperature air conditioner, and the humidity is controlled by an industrial-grade air humidifier with a constant-humidity mode.
In the step 2, the fermentation temperature is preferably controlled to be 28-32 ℃, the humidity of the fermentation environment is 80-85%, and the fermentation time is 48-60 hours.
In the step 3, the fermented medicated leaven is preferably subjected to ventilation drying at the temperature of 55-60 ℃ for 36-48 hours.
The invention has the following beneficial effects:
1. the invention changes the preparation of the medicated leaven from the traditional, seasonal and empirical fermentation control mode into the standard, controllable and perennial production fermentation preparation mode, so that the fermentation process of the medicated leaven is standardized, unified and safe, is not limited by natural conditions, and realizes the annual continuous production.
2. The method has the advantages of short fermentation time, high fermentation efficiency and controllable fermentation conditions, so that the fermentation of the medicated leaven is more sufficient. Through liquid chromatography detection, the contents of fingerprint substances such as quercetin, quercetin and luteolin are obviously improved compared with the contents of fingerprint substances in the traditional fermentation mode, namely 152.4%, 65.7% and 137.3% respectively. And has effects of resolving food stagnation, invigorating stomach and spleen, relieving inflammation, and killing bacteria.
3. The finished product of the medicated leaven prepared by the invention is characterized in that the microbial population and abundance of the medicated leaven are subjected to genus level identification, no aspergillus flavus pollution is found, the quantity and variety of beneficial microbes are large, and the mixed bacteria pollution in the medicated leaven processing process is reduced, wherein the main microbial population and abundance are Trichoderma (16.3%), Fusarium (12.1%), Pestalotiopsis (12.1%), Mortierella (Mortierella, 8.7%), Beauveria (7%), Chaetomium (8.7%) and the like.
Drawings
FIG. 1 is a layout of a fermentation plant.
FIG. 2 is a graph showing appearance characteristics of a medicated leaven sample obtained in example 1.
FIG. 3 is a liquid chromatogram of fingerprint of quercetin, quercetin and luteolin standard.
FIG. 4 is a fingerprint substance liquid chromatogram of the medicated leaven sample obtained in example 1.
FIG. 5 is a liquid chromatogram of a commercially available sample of Massa Medicata Fermentata.
FIG. 6 shows the results of identification of fungal population and abundance genus levels of the Massa Medicata Fermentata sample obtained in example 1.
Detailed Description
The invention will be further described in detail with reference to the following figures and examples, but the scope of the invention is not limited to these examples.
Example 1
Step 1, taking the raw materials according to the following proportions: 0.25kg of sweet wormwood, 0.25kg of polygonum hydropiper, 0.25kg of xanthium sibiricum, 3kg of phaseolus calcaratus, 3kg of bitter almond, 25kg of wheat bran and 50kg of flour, and the components are crushed and sieved by a 60-mesh sieve. Wherein semen Phaseoli is pulverized independently, added into cold water 10 times the weight of semen Phaseoli, stirred uniformly, heated to boiling, continuously stirred during heating process to prevent scorching, and boiled for 10min to obtain viscous semen Phaseoli water. Adding boiled semen Phaseoli water into the above raw material powder while hot, stirring well with a blender, adjusting water content in the raw material to 40 wt.% by adding boiling water, and raising the temperature of the yeast material to 70 + -5 deg.C. And putting the premixed yeast material into a yeast making mold, pressing into yeast blocks with the square of 2 +/-0.5 cm, and putting into a fermentation plate, wherein the height of the yeast material is about 4-5 cm.
Step 2: placing the fermentation plate in the step 1 on a fermentation frame 4 of the Massa Medicata Fermentata in a fermentation workshop (shown in figure 1) with ten thousand grades of cleanliness, using an air self-cleaning device 1 to keep the cleanliness of air at 1 ten thousand grades, and keeping the pressure of the fermentation workshop to be higher than the pressure of an unclean area by 10 Pa; the constant temperature of the fermentation workshop is kept to be 30 +/-2 ℃ by using a constant temperature air conditioner 2; the industrial-grade air humidifier 3 with a constant humidity mode is used for controlling the environmental humidity of the fermentation workshop to be 80 +/-5%, and the fermentation time is 48 h. The surface of the koji block is coated with yellow and white mildew (see figure 2), and has special fermentation fragrance.
And step 3: and (3) putting the fermented medicated leaven to 55-60 ℃, and carrying out ventilation drying for 48h until the leaven material is completely dried to obtain the medicated leaven finished product.
Example 2
Step 1, taking the raw materials according to the following proportions: 1kg of sweet wormwood, 1kg of polygonum hydropiper, 1kg of xanthium sibiricum, 5kg of phaseolus calcaratus, 5kg of bitter almond, 30kg of wheat bran and 50kg of flour, and the components are crushed and sieved by a 60-mesh sieve. Wherein semen Phaseoli is pulverized independently, added into cold water 10 times the weight of semen Phaseoli, stirred uniformly, heated to boiling, continuously stirred during heating process to prevent scorching, and boiled for 10min to obtain viscous semen Phaseoli water. Adding boiled semen Phaseoli water into the above raw material powder while hot, stirring well with a blender, adjusting water content in the raw material to 40 wt.% by adding boiling water, and raising the temperature of the yeast material to 70 + -5 deg.C. And putting the premixed yeast material into a yeast making mold, pressing into yeast blocks with the square of 2 +/-0.5 cm, and putting into a fermentation plate, wherein the height of the yeast material is about 4-5 cm.
Step 2: placing the fermentation plate in the step 1 on a fermentation frame 4 of the Massa Medicata Fermentata in a fermentation workshop (shown in figure 1) with ten thousand grades of cleanliness, using an air self-cleaning device 1 to keep the cleanliness of air at 1 ten thousand grades, and keeping the pressure of the fermentation workshop to be higher than the pressure of an unclean area by 10 Pa; the constant temperature of the fermentation workshop is kept to be 28 +/-2 ℃ by using a constant temperature air conditioner 2; the industrial-grade air humidifier 3 with a constant humidity mode is used for controlling the environmental humidity of the fermentation workshop to be 70 +/-5%, and the fermentation time is 72 h. The surface of the koji block is coated with yellow and white mildew, and has special fermentation fragrance.
And step 3: and (3) putting the fermented medicated leaven to 55-60 ℃, and carrying out ventilation drying for 48h until the leaven material is completely dried to obtain the medicated leaven finished product.
High Performance Liquid Chromatography (HPLC) is adopted to detect the effective components of the finished product of the medicated leaven obtained in the example 1, and the contents of fingerprint substances, namely quercetin, quercetin and luteolin in the finished product of the medicated leaven are determined, wherein the specific method comprises the following steps:
1: preparation of Massa Medicata Fermentata HPLC test sample solution
Crushing the prepared finished product of the medicated leaven, sieving the crushed medicated leaven with a 100-mesh sieve, accurately weighing 10.00g of medicated leaven powder, adding 50mL of analytically pure methanol, condensing and refluxing for 60min at 85 ℃, filtering, evaporating and concentrating the filtrate to a volume of a 10mL volumetric flask, and filtering with a 0.22 mu m microporous membrane to obtain a sample solution.
2: preparation of mixed reference fingerprint substance standard solution
Precisely weighing 0.0035g of quercetin, quercetin and luteolin respectively, dissolving with methanol, and metering to 100mL to obtain 35 μ g/mL standard sample solution, wherein the chromatogram is shown in FIG. 3. Wherein the retention time of quercetin is 19.212min, the retention time of quercetin is 24.229min, and the retention time of luteolin is 26.883 min.
3: measurement of fingerprint substance content in finished product of medicated leaven
And (3) injecting the test sample solution obtained in the step (1) into HPLC to detect the contents of fingerprint substances such as quercetin, quercetin and luteolin. The HPLC conditions were as follows: venusil ASB C18 column (4.6X 250mm, 5 μm) at 30 ℃. The mobile phase is methanol (A) -0.2% phosphoric acid water solution (B), the concentration of the mobile phase (A) is linearly increased from 35% to 65% within 0-30 min, the concentration of the mobile phase (A) is decreased from 65% to 35% within 30-40 min, the flow rate is 1.0mL/min, the sample injection volume is 10 mu L, and the detection wavelength is 360 nm. The liquid chromatogram of the test sample is shown in FIG. 4, wherein the retention time of quercetin is 19.017min, the content is 15.4 μ g/mL, the retention time of quercetin is 24.229min, the content is 5.2 μ g/mL, the retention time of luteolin is 26.883min, and the content is 8.6 μ g/mL. The content of the medicated leaven is respectively improved by 152.4%, 65.7% and 137.3% compared with that of the commercial medicated leaven finished product (see figure 5). As can be seen from fig. 6, the finished product of the medicated leaven obtained in example 1 has no aspergillus flavus pollution, and has a large number and variety of beneficial microorganisms, and the main microbial population and abundance are Trichoderma (Trichoderma, 16.3%), Fusarium (12.1%), Pestalotiopsis (12.1%), Mortierella (Mortierella, 8.7%), Beauveria (Beauveria, 7%), Chaetomium (8.7%), and the like.

Claims (6)

1. A scale controllable fermentation method of Massa Medicata Fermentata with ten thousand grades of cleanliness is characterized by comprising the following steps:
step (1): pulverizing herba Artemisiae Annuae, herba Polygoni Hydropiperis, herba Xanthii, semen Phaseoli, semen Armeniacae amarum, testa Tritici, and flour, adding water, stirring, and making starter;
step (2): placing the yeast material obtained in the step (1) in a fermentation workshop with ten thousand grades of cleanliness, and controlling the fermentation conditions as follows: the air cleanliness is more than 1 ten thousand grade, the pressure of a fermentation workshop is kept more than 10Pa higher than that of an unclean area, the fermentation temperature is 25-35 ℃, the humidity of the fermentation environment is 70-90%, and the fermentation time is 48-72 hours;
and (3): and (3) ventilating and drying the fermented medicated leaven at 40-60 ℃ to constant weight.
2. The scale controllable fermentation method of Massa Medicata Fermentata with ten thousand grades of cleanliness according to claim 1, which is characterized in that: in the step (1), the raw materials are mixed according to the following mass portions: 0.2-2 parts of sweet wormwood, 0.2-2 parts of polygonum hydropiper, 0.2-2 parts of xanthium sibiricum, 2-5 parts of phaseolus calcaratus, 2-5 parts of bitter almond, 20-50 parts of wheat bran and 20-50 parts of flour, and the components are ground and sieved by a sieve of 40-60 meshes.
3. The scale controllable fermentation method of Massa Medicata Fermentata with ten thousand grades of cleanliness according to claim 1, which is characterized in that: in the step (1), the water content in the koji material for making the koji is 35-45 wt.%.
4. The scale controllable fermentation method of Massa Medicata Fermentata with ten thousand grades of cleanliness according to claim 1, which is characterized in that: in the step (2), the fermentation workshop with ten thousand grades of cleanliness controls the cleanliness through an air self-cleaning device, controls the temperature through a constant-temperature air conditioner, and controls the humidity through an industrial-grade air humidifier with a constant-humidity mode.
5. The scale controllable fermentation method of Massa Medicata Fermentata with ten thousand grades of cleanliness according to claim 1, which is characterized in that: in the step (2), the fermentation temperature is controlled to be 28-32 ℃, the humidity of the fermentation environment is controlled to be 80-85%, and the fermentation time is controlled to be 48-60 hours.
6. The scale controllable fermentation method of Massa Medicata Fermentata with ten thousand grades of cleanliness according to claim 1, which is characterized in that: in the step (3), the fermented medicated leaven is subjected to ventilation drying at the temperature of 55-60 ℃ for 36-48 hours.
CN202011506340.3A 2020-12-18 2020-12-18 Large-scale controllable fermentation method of Massa Medicata Fermentata with ten thousand-level cleanliness Pending CN112603969A (en)

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CN108938949A (en) * 2018-08-13 2018-12-07 雅安迅康药业有限公司 A kind of natural material highland barley monascus medicine materical crude slice and preparation method and application
CN110025735A (en) * 2019-04-19 2019-07-19 河南省青山药业股份有限公司 A kind of preparation method of Medicated Leaven

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