CN116531456A

CN116531456A - Fritillaria cirrhosa formula granule intermediate and preparation method thereof

Info

Publication number: CN116531456A
Application number: CN202310499059.9A
Authority: CN
Inventors: 张志强; 刘天祎; 冯京; 赵胜达; 张思琦; 周永康; 程立伟; 董晨虹
Original assignee: Beijing Tcmages Pharmaceutical Co Ltd
Current assignee: Beijing Tcmages Pharmaceutical Co Ltd
Priority date: 2023-05-05
Filing date: 2023-05-05
Publication date: 2023-08-04

Abstract

The invention provides a fritillaria cirrhosa formula granule intermediate and a preparation method thereof. A preparation method of a fritillaria cirrhosa formula granule intermediate comprises the following steps: filtering to obtain Bulbus Fritillariae Cirrhosae water extractive solution; concentrating the water extract to a relative density of 1.01-1.04, preheating the concentrated solution at 50-60 ℃, filtering the hot concentrated solution under the condition of 250-300 meshes to obtain filtrate, and finally spray-drying the filtrate to obtain the water extract. The method can solve the problem of lower powder yield when the conventional spray drying method is adopted to dry the fritillaria cirrhosa water extract in the prior art, and effectively obtain the fritillaria cirrhosa formula particle intermediate with better state, fine powder quality, good dissolubility and more than 85 percent of spray-dried powder yield.

Description

Fritillaria cirrhosa formula granule intermediate and preparation method thereof

Technical Field

The invention relates to the field of traditional Chinese medicines, in particular to a fritillaria cirrhosa formula granule intermediate and a preparation method thereof.

Background

Bulbus Fritillariae Cirrhosae is dry bulb of Bulbus Fritillariae Thunbergii Fritillaria delavayi Franch of Liliaceae, and is mainly produced in Sichuan, tibet, qinghai, gansu, etc., and is a well-known medicinal material in the places of Sichuan birth canal. Bulbus Fritillariae Cirrhosae has bitter taste, sweet taste, slightly cold nature, and lung and heart meridian entered property, has effects of clearing heat, moistening lung, resolving phlegm, relieving cough, resolving hard mass, and resolving carbuncle, and can be used for treating lung heat dry cough, dry cough with little phlegm, yin deficiency with tuberculosis, blood in phlegm, scrofula, acute mastitis, pulmonary abscess, etc. The alkaloid fritillary bulb alkaloid has the effects of relieving cough, eliminating phlegm, spasmolysis, resisting bacteria and reducing blood pressure, is a main anti-inflammatory active ingredient in the fritillary bulb, and is consistent with the efficacy of relieving cough of the fritillary bulb.

At present, the clinical medicinal mode of the fritillary bulb is powder grinding, taking or decocting in water, and the fritillary bulb medicinal materials, fritillary bulb decoction pieces, fritillary bulb powder and fritillary bulb powder formula granules are sold in the market, but the fritillary bulb powder formula granules are obtained by granulating fritillary bulb powder after adding auxiliary materials, have no essential difference with the fritillary bulb powder, have poor water solubility and are not beneficial to patients to take. The traditional Chinese medicine formula granule is generally prepared by performing procedures such as water extraction, separation, concentration, drying, granulation and the like on single traditional Chinese medicine decoction pieces, and preparing the traditional Chinese medicine decoction pieces into decoction-free granules, wherein the water solubility of the formula granule meets the requirements of Chinese pharmacopoeia, is beneficial to patients to take, and improves the compliance of the patients. The traditional usage of fritillary medicinal materials in folk is decoction, and fritillary bulb is used as a clinically common traditional Chinese medicinal material, but the preparation method of the water extract formula granule is not explicitly reported at present.

In the preparation process of the traditional Chinese medicine formula granule, the preparation of an intermediate is a key link, and common drying modes for the preparation of the intermediate comprise reduced pressure drying and spray drying. Although extremely high powder yield can be obtained by adopting the reduced pressure belt type drying, the concentration density required by the reduced pressure drying in production needs to be more than 1.20, and as the fritillaria cirrhosa water extract contains a large amount of starch components, the higher the relative density of concentration is, the higher the concentration difficulty is, and particularly, the precipitate which is difficult to redissolve can appear when the relative density is more than 1.04, so that the preparation of fritillaria cirrhosa formula particle intermediates by adopting the reduced pressure drying has more technical difficulty. In addition, the dry extract after drying under reduced pressure has a hard texture, is difficult to grind, and has poor solubility. Although the problem of poor solubility existing in the reduced pressure belt drying can be solved by adopting a spray drying mode, when the intermediate of the formula particles is prepared by adopting the spray drying mode, the prepared spray drying powder has the problem of lower powder yield no matter how the types of auxiliary materials are added and the technological parameters of the drying step are regulated, and the highest powder yield can only reach about 60.0 percent under the condition of the conventional technological parameters, and is difficult to reach more than 80 percent; therefore, there is a problem that the spray-drying method causes a large loss of the spray-dried powder, resulting in a large increase in production cost.

Disclosure of Invention

The invention aims to solve the technical problem that the powder yield is lower when the conventional spray drying mode is adopted to dry the fritillaria cirrhosa water extract in the prior art; thereby providing the fritillaria cirrhosa formula particle intermediate with better state, fine powder quality and good solubility, and providing the preparation method of the fritillaria cirrhosa formula particle intermediate with obviously improved powder yield.

A preparation method of a fritillaria cirrhosa formula granule intermediate comprises the following steps:

filtering to obtain water extract of Bulbus Fritillariae Cirrhosae, concentrating the water extract to relative density of 1.01-1.04 to obtain concentrated solution, filtering the concentrated solution under 250 mesh or above to obtain filtrate, and spray drying the filtrate.

Filtering the concentrated solution under the condition of 250-300 meshes to obtain filtrate;

and/or, preheating the concentrated solution to 50-60 ℃ and filtering the hot concentrated solution;

and/or, in the spray drying, the air inlet temperature is 140-160 ℃, and the air outlet temperature is 70-90 ℃.

The water extract is obtained through the following steps:

decocting for 1-3 times, adding water with the quantity of 6-12 times of decoction pieces during decoction, decocting for 30-90 minutes after boiling, and filtering to obtain water extract.

The water extract is obtained through the following steps:

decocting twice, wherein the decoction pieces are added with 12 times of water, the decoction is boiled for 30 minutes, the decoction pieces are added with 11 times of water, the decoction is boiled for 30 minutes, and the water extract is obtained by filtering.

The filtering mode adopted in the water extract obtaining process is that filtering is carried out by adopting filter cloth with 100-200 meshes.

The concentration temperature is not higher than 85 ℃, and the concentration time is not higher than 24 hours.

And no auxiliary materials are added in the spray drying process.

The fritillaria cirrhosa formula particle intermediate is prepared by adopting the preparation method of the fritillaria cirrhosa formula particle intermediate.

The paste yield of the fritillaria cirrhosa formula particle intermediate is 17% -25%; the extract range is not less than 28.0%; the content range of uridine is 0.40 mg/g-0.80 mg/g; guanosine content range is 0.20 mg/g-0.40 mg/g; the adenosine content ranges from 0.40mg/g to 0.70mg/g; the content range of the fritillary bulb alkali is 0.10 mg/g-0.70 mg/g; the range of uridine transfer rate is 40% -75%, the range of guanosine transfer rate is 35% -65%, the range of adenosine transfer rate is 45% -95%, and the range of fritillary bulb alkali transfer rate is 25% -75%.

The technical scheme of the invention has the following advantages:

1. the invention provides a preparation method of a fritillaria cirrhosa formula granule intermediate, which adopts a water decoction method to extract fritillaria cirrhosa to obtain water extract, the water extract is concentrated to have a relative density of 1.01-1.04 to obtain concentrated solution, the concentrated solution is filtered under the condition of more than 250 meshes to obtain filtrate, and finally the filtrate is subjected to spray drying to obtain the fritillaria cirrhosa formula granule intermediate; the method can still obviously improve the powder yield of the intermediate of the formula particles of the bulbus fritillariae cirrhosae compared with the powder yield of the intermediate of the formula particles of the bulbus fritillariae cirrhosae which is about 60.0 percent obtained by conventional process parameter experiments even if no auxiliary materials are added.

2. According to the invention, the concentrated solution is filtered under the condition of 250-300 meshes, and is matched with the concentrated solution to be preheated to 50-60 ℃ and then filtered while the concentrated solution is hot, and the air inlet temperature is 140-160 ℃ and the air outlet temperature is 70-90 ℃ in the spray drying, so that the powder yield of the fritillaria cirrhosa formula granule intermediate can be improved to more than 80%, even more than 85%, and the method is energy-saving and efficient, and is suitable for large-scale industrial production.

3. The fritillaria cirrhosa formula granule intermediate powder prepared by the invention is fine and smooth and has good water solubility, and meanwhile, the content of each index component can be ensured to be consistent with that of the fritillaria cirrhosa standard decoction, so that the drug effect of the finished product granule is effectively ensured.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.

FIG. 1 is a process flow diagram of the present invention;

FIG. 2 is a characteristic spectrum of a standard decoction obtained from 17 batches of fritillaria cirrhosa decoction pieces in the present invention.

Detailed Description

The specific experimental procedures or conditions are not noted in the examples and may be followed by the operations or conditions of conventional experimental procedures described in the literature in this field. The reagents or apparatus used were conventional reagent products commercially available without the manufacturer's knowledge.

Example 1

A preparation method of Bulbus Fritillariae Cirrhosae granule intermediate, as shown in figure 1, comprises the following steps:

coarse particles prepared by pretreating Bulbus Fritillariae Cirrhosae (Bolbostemma Pentaphyllum) (YP 2022030318) decoction pieces are mixed with powder capable of passing through 4 mesh sieve but not more than 20% of 10 mesh sieve, and the diameter of the coarse particles after pretreatment is about 3-7 mm. Extracting coarse particles for 2 times, decocting with 12 times of water, boiling, heating for 30 min, decocting with 11 times of water, boiling, heating for 30 min, filtering with 150 mesh filter cloth, mixing filtrates, concentrating under reduced pressure at 65deg.C to relative density of 1.01 (60deg.C), preheating the concentrated solution in water bath at 60deg.C before spray drying, filtering with 300 mesh filter cloth while hot, and spray drying to obtain Bulbus Fritillariae Cirrhosae formula granule intermediate, wherein the parameters of spray drying are as follows:

auxiliary materials: 0, preheating temperature of liquid medicine: 60 ℃, the air inlet temperature of the spray tower: 160 ℃ and 90 ℃ of the air outlet temperature of the spray tower.

Examples 2 to 10

The preparation method of the fritillaria cirrhosa formula granule intermediate is different from example 1 in terms of process parameter conditions, specifically, the mesh number of filtration, the density of the concentrated feed liquid, the spray drying parameters and the like, and specifically, the following table 1 is provided:

TABLE 1

	The difference from example 1 is that:
		example 2	Concentrating to relative density of 1.04 (60deg.C)
Example 3	Concentrating to a relative density of 1.02 (60deg.C)
		Example 4	Beta-cyclodextrin 9% by weight of the concentrate is added during spray drying
Example 5	Adding 9% dextrin into the concentrated solution during spray drying
		Example 6	Air inlet temperature of the spray tower: 140 ℃ and 70 ℃ of air outlet temperature of the spray tower
Example 7	The mesh number of the concentrated solution filtration is 250 meshes
		Example 8	The mesh number of the concentrated solution filtration is 350 meshes
Example 9	The air inlet temperature of the spray tower is 130 ℃, and the air outlet temperature of the spray tower is 60 DEG C
		Example 10	The concentrate is not preheated but refrigeratedFiltering with 300 mesh filter cloth after refrigeration to obtain filtrate

The powder yield of the fritillaria cirrhosa intermediates prepared in the above embodiment is shown in the following table 11, and compared with about 60% of fritillaria cirrhosa intermediates prepared by direct spray drying in the prior art, the powder yield of the fritillaria cirrhosa intermediates prepared in the embodiment of the application is obviously improved. However, the filtration of 350 meshes is very difficult, and the powder yield of the embodiment 9-10 is only 75.8-77.1%, so that the preferred concentrated solution is filtered under the condition of 250-300 meshes, and is mixed with the concentrated solution to be preheated to 50-60 ℃ and then filtered while hot, and the concentrated solution is mixed with the concentrated solution by spray drying, wherein the air inlet temperature is 140-160 ℃ and the air outlet temperature is 70-90 ℃; can effectively ensure that the powder yield of the fritillaria cirrhosa intermediate reaches more than 80 percent.

Comparative example 1

This comparative example is different from example 1 in that extraction was performed in the same manner as in example 1 and filtration was performed using a conventional 150 mesh filter cloth to obtain an aqueous extract, which was then concentrated to different relative densities shown in table 2, without adding an auxiliary material, and spray-dried under the conditions shown in table 2.

TABLE 2

Comparative example 2

The comparative example differs from example 1 in that a different drying mode from example 1, i.e., belt drying, was employed, and the specific procedure was as follows: concentrating the same extract as in comparative example 1 to a relative density of 1.05g/cm ³ . Then, drying under reduced pressure was performed in the manner shown in the following Table 3.

TABLE 3 Table 3

Experimental example 1

Obtaining standard decoction, and obtaining similarity between extract yield, active ingredient content and transfer rate of standard decoction and characteristic spectrum of decoction pieces

Preparation of a standard decoction of fritillaria cirrhosa decoction pieces: the same pretreatment method as in example 1 was used to obtain coarse particles from fritillaria cirrhosa decoction pieces. Soaking coarse particles in water of 6 times of decoction pieces for 30 min, boiling with strong fire, decocting with slow fire for 30 min, filtering with 150 mesh filter cloth, and rapidly cooling; decocting with water 5 times of decoction pieces, boiling with strong fire, decocting with slow fire for 20 min, filtering with 150 mesh filter cloth while hot, and rapidly cooling; mixing the two decoctions, concentrating under reduced pressure (65deg.C), concentrating to a feed-liquid ratio of about 1:1, and lyophilizing.

Collecting 17 batches of fritillaria cirrhosa standard decoction pieces, obtaining a paste rate, measuring the contents of nucleoside components and alkaloid components, and calculating a transfer rate; simultaneously obtaining a characteristic map and calculating the similarity between the characteristic map and the corresponding decoction pieces, wherein:

1.1 determination of the paste yield

The sampling amount of the fritillary bulb decoction pieces is (M) _Medicine ) Placed in a weighed beaker (M ₀ ) After cooling the extract, the weight (M ₁ ) Shaking, weighing 1/10 of the total weight of the first decoction and the second decoction, precisely weighing (M _Sample ) Placed in a constant weight evaporation dish (M _Dish ) Evaporating in water bath, drying at 105deg.C for 5 hr, taking out, cooling to room temperature in a dryer, and weighing (M) ₂ ) And (3) calculating the paste rate, drying at the temperature for 1 hour, cooling, weighing, and calculating the paste rate until the values of the paste rate obtained from two successive times are within 1 percent.

1.2 determination of the active ingredient content

Detecting the content of uridine, guanosine, adenosine and fritillary bulb alkali in the standard decoction by adopting a conventional high performance liquid chromatography; because the specific detection method is a conventional method, the detailed description thereof will be omitted.

1.3 method for detecting transfer rate

Calculating the transfer rate of the corresponding active ingredient based on the content of the corresponding active ingredient obtained in 1.2 according to the following transfer rate formula;

1.4 similarity detection

And (3) obtaining a corresponding characteristic spectrum by adopting the high performance liquid chromatography which is the same as that in 1.2, and obtaining the similarity of the characteristic spectrum.

The test results of the standard decoction obtained from 17 batches of fritillaria cirrhosa decoction pieces in this experimental example are shown in tables 4 to 8 and fig. 2 below.

TABLE 4 results of paste yield of standard decoction of fritillaria cirrhosa decoction pieces of batch 17

TABLE 5 determination of uridine content of freeze-dried powder of Bulbus Fritillariae Cirrhosae standard decoction of 17 batch and calculation of transfer rate

Table 6 determination results of the content of the freeze-dried powder of the fritillary bulb alkali in the fritillary bulb standard decoction of 17 batches

TABLE 7 retention time and relative retention time for the detection of the characteristic profile of the freeze-dried powder of the fritillaria cirrhosa standard decoction of batch 17

TABLE 8 similarity calculation results

The characteristic spectrum of the freeze-dried powder of the standard decoction of the fritillaria cirrhosa of 17 batches has corresponding peaks at the positions corresponding to the reference substances of the reference substances and the reference peaks of the reference medicinal materials, and the similarity between batches is between 0.900 and 1.000, which indicates that the substance basis transfer of the freeze-dried powder of the standard decoction of the fritillaria cirrhosa is stable.

According to the technical requirements of quality control and standard formulation of traditional Chinese medicine formula particles, 17 batches of fritillaria cirrhosa decoction pieces are taken as samples for the final result of research of standard decoction:

the paste yield range of the fritillaria cirrhosa standard decoction is determined to be 17.0% -25.0%;

the content range of uridine in the fritillaria cirrhosa standard decoction is 0.50 mg/g-0.90 mg/g; guanosine content range is 0.20 mg/g-0.50 mg/g; the adenosine content ranges from 0.45mg/g to 0.85mg/g; the content range of the fritillary bulb alkali is 0.10 mg/g-0.80 mg/g;

the uridine transfer rate ranges from 40.0% to 75.0%; the guanosine transfer rate ranges were defined as: 35.0 to 65.0 percent; the adenosine transfer rate range was defined as: 45.0% -95.0%; the transfer rate of the fritillary bulb alkali ranges from 25.0% to 75.0%;

the chromatographic sample should present 6 characteristic peaks and should correspond to the retention time of 6 characteristic peaks in the chromatographic peak of the reference substance of the reference medicinal material, the corresponding peak of the reference substance of the fritillary bulb is taken as the S peak, the relative retention time of each characteristic peak and the S peak is calculated, the relative retention time is within +/-10% of the specified value, and the specified value is: 0.56 (peak 1), 0.64 (peak 2), 0.68 (peak 3), 1.00 (peak 4S), 1.07 (peak 5), 1.66 (peak 6);

in the process of standard decoction of the fritillaria cirrhosa decoction pieces, target peaks marked by fingerprint patterns are not lost, and stable transfer is realized, so that chemical components represented by the characteristic peaks are transferred from decoction pieces to standard decoction pieces better.

Experimental example 2

The fritillaria cirrhosa formula particle intermediate prepared by the examples and the comparative examples is subjected to the detection method in experimental example 1 to obtain the paste yield, the content of nucleoside components and alkaloid components is measured, and the characteristic spectrum is obtained and the similarity between the characteristic spectrum and the characteristic spectrum of the standard decoction is calculated.

And simultaneously, the solid content and the powder yield of the fritillaria cirrhosa formula granule intermediate are obtained.

The detection method of the solid content comprises the following steps: and (3) drying the evaporation pan to constant weight, accurately weighing the mass M1 of the evaporation pan to obtain concentrated solution, placing the concentrated solution in the evaporation pan, accurately weighing the total mass M2 of the evaporation pan and the concentrated solution, evaporating the concentrated solution in a water bath, fully drying the concentrated solution in an oven to constant weight, weighing the concentrated solution M3, and calculating the solid content and the powder yield percent of the fritillaria cirrhosa formula particle intermediate prepared in the above examples and comparative examples by adopting the following formula.

Solid content = (M3-M1)/(M2-M1) ×100%

The results of the tests of the examples and comparative examples are shown in the following tables 9 to 11:

TABLE 9

Table 10

TABLE 11

Experimental example 3

3 batches of the fritillaria cirrhosa formula granule intermediate were prepared by the method of example 1, and were tested by the method of experimental example 1, the experimental procedure is shown in table 12 below, and 3 batches of experimental results were obtained, and the results are shown in tables 13-14.

Table 12

TABLE 13

TABLE 14

3 batches of small test evidence extract, extract yield and uridine, guanosine, adenosine and fritillary bulb alkali transfer rate are in a standard range; the characteristic peaks of the bulbus fritillariae cirrhosae standard decoction can be in one-to-one correspondence with the characteristic peaks of the characteristic spectrum in the small test evidence process (extraction, concentration and drying), and the 6 characteristic peaks can realize stable transmission.

The test result of 3 batches meets the requirement limit of the fritillaria cirrhosa formula granule, and 6 characteristic peaks in the fritillaria cirrhosa standard decoction control map are stably transferred in the test production process. The adopted technological parameters can ensure that the technological result meets the requirements, and according to the characteristic spectrum research result, the technological sample can keep consistent with the standard decoction quality.

Experimental example 4

1. Research on extraction process

The experimental process comprises the following steps: the extraction process of the fritillaria cirrhosa is optimized through an orthogonal test. Combining the main factors influencing the extraction efficiency of the variety, selecting three factors of extraction times, water addition amount and extraction time for investigation, taking the extraction rate of the fritillaria cirrhosa, the content of nucleoside components and alkaloid components and the transfer rate as evaluation indexes, and using L ₉ (3 ⁴ ) Orthogonal table the test was arranged and the orthogonal test table is shown in table 15.

TABLE 15 fritillaria cirrhosa orthogonal test chart

Wherein: 6 (5) represents that the water addition amount for the first extraction is 6 times and the water addition amount for the second extraction is 5 times; 6 (5, 5) represents that the water addition amount of the first extraction is 6 times, the water addition amount of the second extraction is 5 times, and the water addition amount of the third extraction is 5 times; by analogy, 12 (11), 60 (60), 90 (90, 90), etc. in the tables are explained in a similar way to 6 (5), and will not be repeated in the present invention.

9 parts of fritillary bulb coarse particles (YP 2022030316) were taken, 200g each, placed in a round-bottomed flask and extracted as described above. Filtering the extracted liquid medicine with 150 mesh filter cloth, cooling to room temperature in water bath, and weighing the total weight of the liquid medicine. Weighing about 1/10 of the total liquid medicine, placing in an evaporation dish (parallel sample) and evaporating in water bath, placing in an oven for drying, weighing, and calculating the paste rate. Concentrating the rest extractive solution at 65deg.C under reduced pressure until the ratio of fluid extract to decoction pieces is about 1:1, transferring to a freeze-drying plate, vacuum freeze-drying, collecting freeze-dried powder, detecting by the method in experimental example 1, and calculating the transfer rate and the similarity.

The results of the detection are shown in tables 16 and 17 below.

TABLE 16 extraction of the extraction and transfer rates of fritillaria cirrhosa from orthogonal experimental results

Table 17 calculation results of similarity of orthogonal feature patterns extracted from Bulbus Fritillariae Cirrhosae

Taking the average value result of the 17 batches of fritillaria cirrhosa standard decoction in the embodiment 1 as a target value, carrying out model prediction by taking the transfer rate of alkaloid components and nucleoside components and the paste yield of the extracting solution as important indexes, comprehensively considering energy consumption and production process loss, setting the paste yield target value as the average value +3% of the paste yield of the current batch of standard decoction, analyzing the fritillaria cirrhosa orthogonal experiment result by using design experert 8.0 software, and screening out the 8 th set of process parameters as optimal parameter conditions by combining the transfer rate prediction value, thereby taking the 8 th set of parameter conditions as the fritillaria cirrhosa extraction process, namely: extracting for 2 times, decocting with 12 times of water for 30 min, decocting with 11 times of water for 30 min.

2. Separation Process study

The experimental process comprises the following steps: three parts of fritillary bulb decoction pieces (YP 2022030316) are taken, 100g of each part is decocted according to a selected extraction process. Filtering the extractive solution with 100 mesh filter cloth, 150 mesh filter cloth and 200 mesh filter cloth, cooling to room temperature in water bath, and weighing the total weight of the medicinal liquid. About 100g of the liquid medicine is weighed, placed in an evaporation dish (parallel sample is taken), evaporated in a water bath, fully dried in an oven, weighed and the paste rate is calculated. Concentrating the rest extractive solution at 65deg.C under reduced pressure until the ratio of fluid extract to decoction pieces is about 1:1, transferring to a freeze-drying plate, vacuum freeze-drying, collecting freeze-dried powder, and detecting and calculating the transfer rate according to the method in experimental example 1, and the detection results are shown in the following table 18.

Table 18 shows the results of the separation process of Bulbus Fritillariae Cirrhosae

Conclusion: different filter cloth is used, no obvious difference is caused in the paste yield, the index component content and the transfer rate, the following production process is considered, the fritillaria cirrhosa formula particle filtration process is consistent with that of the standard decoction, and the 150-mesh filter cloth is used for filtration.

3. Research on concentration process

The experimental process comprises the following steps: 400g of fritillaria cirrhosa decoction pieces (YP 2022030316) are taken, the decoction is decocted according to the technological parameters of the standard fritillaria cirrhosa decoction, the extract is filtered by a filter cloth with 150 meshes, the filtrates are combined, cooled and the total weight of the liquid medicine is weighed. About 100g of the extract is weighed, placed in an evaporation dish (parallel sample is taken), evaporated in a water bath, placed in an oven for full drying, weighed and the paste rate is calculated. The remaining medicinal liquid was concentrated to about 800ml, and the weight of the concentrated solution was measured. The concentrated liquid medicine is divided into 30 parts, each part is placed into a 50ml centrifuge tube for weighing and sealing, water bath heating (different temperature water baths are prepared in advance) is adopted, the temperature is respectively set to 65 ℃ (10 parts), 75 ℃ (10 parts) and 85 ℃ (10 parts), sampling is respectively carried out at 0h, 3h, 6h, 9h, 15h and 24h (parallel sampling), and the mixture is placed at room temperature to serve as samples of different concentration temperatures and time of fritillaria cirrhosa. After taking 9ml of the sample and adding methanol to a 10ml volumetric flask for constant volume, the method in experimental example 1 was used for detection and similarity calculation.

The experimental results are shown in tables 19 to 20 below.

TABLE 19 concentration of the ingredients at different concentration temperatures for different times

Table 20 similarity calculation of characteristic patterns at different concentration times at 65-85 ℃ and characteristic patterns at 0h

In the concentrating process of the fritillaria cirrhosa extract, the heating temperature is below 85 ℃ and the heating time is within 24 hours, so that the extract material basis is ensured not to change obviously, and the content loss of uridine, guanosine, adenosine and fritillaria cirrhosa alkali is small. Therefore, the process for producing and concentrating the fritillaria cirrhosa formula particles can be set as follows: the concentration time is not more than 24 hours below 85 ℃.

It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.

Claims

1. A preparation method of a fritillaria cirrhosa formula particle intermediate is characterized by comprising the following steps:

2. The preparation method according to claim 1, wherein the concentrated solution is filtered under the condition of 250-300 meshes to obtain filtrate;

3. The preparation method according to claim 1 or 2, wherein the aqueous extract is obtained by:

4. The method according to claim 3, wherein the water extract is obtained by the steps of:

5. The method according to claim 3 or 4, wherein the water extract is obtained by filtering with 100-200 mesh filter cloth.

6. The process according to any one of claims 1 to 5, wherein the concentration is carried out at a temperature of not more than 85 ℃ for a period of not more than 24 hours.

7. The method according to any one of claims 1 to 6, wherein no auxiliary material is added during the spray drying.

8. The fritillaria cirrhosa formula particle intermediate is characterized in that the fritillaria cirrhosa formula particle intermediate is prepared by adopting the preparation method of the fritillaria cirrhosa formula particle intermediate in any one of claims 1-7.

9. The fritillaria cirrhosa formula particle intermediate of claim 8, wherein the fritillaria cirrhosa formula particle intermediate has a paste yield of 17% -25%;

and/or, the extract range of the intermediate of the fritillaria cirrhosa formula particle is not less than 28.0%;

and/or the uridine content of the fritillaria cirrhosa formula granule intermediate ranges from 0.40mg/g to 0.80mg/g;

and/or, the guanosine content range of the fritillaria cirrhosa formula granule intermediate is 0.20 mg/g-0.40 mg/g;

and/or the adenosine content of the intermediate of the fritillaria cirrhosa formula particle ranges from 0.40mg/g to 0.70mg/g;

and/or the content range of the fritillary bulb alkali of the fritillary bulb prescription granule intermediate is 0.10 mg/g-0.70 mg/g.

10. The fritillaria cirrhosa formula particle intermediate of claim 8 or 9, wherein the fritillaria cirrhosa formula particle intermediate has a uridine transfer rate ranging from 40% to 75%;

and/or, the guanosine transfer rate range of the fritillaria cirrhosa formula granule intermediate is 35% -65%;

and/or, the adenosine transfer rate of the fritillaria cirrhosa formula granule intermediate ranges from 45% to 95%;

and/or the fritillary bulb base transfer rate of the fritillary bulb formula particle intermediate ranges from 25% to 65%.