CN115317588B

CN115317588B - Preparation method of Baoyuan decoction, baoyuan extract and Baoyuan solid preparation

Info

Publication number: CN115317588B
Application number: CN202211173733.6A
Authority: CN
Inventors: 孔令梅; 程杰; 钤莉妍; 刘海滨; 王中超; 王延涛; 齐晓丹; 马立平; 张燕; 赵海晴; 杨海菊; 李士栋
Original assignee: Dong E E Jiao Co Ltd
Current assignee: Dong E E Jiao Co Ltd
Priority date: 2022-09-26
Filing date: 2022-09-26
Publication date: 2024-04-05
Anticipated expiration: 2042-09-26
Also published as: CN115317588A

Abstract

The invention relates to the technical field of medicines, in particular to a preparation method of a Baoyuan decoction, baoyuan extract and Baoyuan solid preparation. The preparation method provided by the invention comprises the following steps: soaking the primordial qi-preserving decoction pieces in water, wherein the mass ratio of the water to the primordial qi-preserving decoction pieces is less than or equal to 14:1, and performing first boiling extraction on the primordial qi-preserving pre-soaking liquid to obtain a first primordial qi-preserving water extract and primordial qi-preserving slag; mixing the primordial qi-preserving medicine residues with water, and performing second boiling extraction, wherein the mass ratio of the water to the primordial qi-preserving medicine residues is less than or equal to 12:1, so as to obtain a second primordial qi-preserving water extract; respectively carrying out first concentration and second concentration on the first water extract and the second water extract, and then merging concentrated solutions to obtain the Baoyuan soup; mixing the Baoyuan decoction with dextrin, and concentrating to obtain Baoyuan extract; and drying and granulating the element-preserving extract to obtain the element-preserving solid preparation. The preparation method provided by the invention comprehensively examines water extraction, concentration and drying, ensures the consistency of the extraction effect of the Baoyuan decoction preparation and the traditional Baoyuan decoction, and can also meet the requirements of modern mass production.

Description

Preparation method of Baoyuan decoction, baoyuan extract and Baoyuan solid preparation

Technical Field

The invention relates to the technical field of medicines, in particular to a preparation method of a Baoyuan decoction, baoyuan extract and Baoyuan solid preparation.

Background

The Baoyuan decoction is written from Ming Sun Zhihong and is named as 71 st party in ancient classical name prescription catalogue (first batch) issued by the national administration of traditional Chinese medicine, and has the effects of invigorating qi, warming yang and mainly treating deficiency of vital energy.

At present, the development of classical famous prescription preparations requires taking a reference sample as a standard, and applying modern production equipment and methods to enable the standard of the obtained preparation to be basically consistent with the standard of the reference sample, wherein decoction can be prepared into granules, so that the preparation of Baoyuan decoction into Baoyuan granules is an important direction for the development of new preparation of Baoyuan decoction at present.

The most key points of the development of the traditional Chinese medicine compound preparation in the classical prescription are as follows: the formulation criteria developed must be substantially identical to the reference sample criteria. The preparation of the Baoyuan granule is different from the preparation of the Baoyuan decoction, and the preparation method is necessarily different, so that the standard of the Baoyuan granule and the Baoyuan decoction is very difficult to be ensured to be consistent, and the main reason is that: the Baoyuan decoction has larger water adding amount (the water adding amount for the first time is 36 times of the mass of the medicinal materials), the extraction rate is close to 90%, and the two extractions are basically complete, so that the standard is higher; when the Baoyuan granule preparation is prepared, if a large amount of water is used for extraction, the high-temperature concentration time before granulation is longer, so that more heat-sensitive active ingredients such as ginsenoside and the like contained in the Baoyuan decoction are easily damaged and decomposed, and the medicinal effect cannot be consistent with the standard of a Baoyuan decoction reference sample.

Disclosure of Invention

Therefore, the invention aims to provide the preparation methods of the Baoyuan decoction, the Baoyuan extract and the Baoyuan solid preparation, and the Baoyuan solid preparation provided by the invention has the advantages of basically consistent quality standard with the Baoyuan decoction reference sample, good solubility, high bioavailability, convenience for taking and carrying and better stability compared with the traditional decoction.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides a preparation method of Baoyuan decoction, which comprises the following steps:

soaking the primordial qi-preserving decoction pieces in water to obtain primordial qi-preserving presoaked liquid; the primordial energy-preserving decoction pieces comprise ginseng decoction pieces, astragalus decoction pieces, cinnamon decoction pieces, licorice decoction pieces and ginger decoction pieces; the mass ratio of the water to the decoction pieces for keeping primordial energy is less than or equal to 14:1;

performing first boiling extraction on the primordial preserving presoaked liquid to obtain first primordial water extract and primordial preserving dregs;

mixing the primordial energy-preserving medicine residues with water, and performing second boiling extraction, wherein the mass ratio of the water to the primordial energy-preserving decoction pieces is less than or equal to 12:1, so as to obtain a second primordial energy-preserving water extract;

respectively carrying out first concentration and second concentration on the first and second water extract to obtain first and second concentrated solutions;

And combining the first and second primordial energy-preserving concentrated solutions to obtain the primordial energy-preserving soup.

Preferably, the mass ratio of the water to the health-care decoction pieces is (8-14) 1; the soaking time is 30-60 min;

the first boiling extraction comprises a heating stage heated by steam and a boiling heat preservation stage heated by steam; the pressure of steam in the heating stage is less than or equal to 0.2MPa; the heat preservation time of the boiling heat preservation stage is 40-50 min, and the steam pressure is 0.02-0.08 MPa.

Preferably, the mass ratio of the water to the Baoyuan decoction pieces is (6-12) 1 during the second boiling extraction; the second boiling extraction comprises a heating stage heated by steam and a boiling heat preservation stage heated by steam; the pressure of steam in the heating stage is less than or equal to 0.2MPa; the heat preservation time of the boiling heat preservation stage is 30-40 min, and the steam pressure is 0.02-0.08 MPa.

Preferably, the mass ratio of the ginseng decoction pieces, the astragalus decoction pieces, the liquorice decoction pieces, the cinnamon decoction pieces and the ginger decoction pieces is 373:746:186:75: (100-300).

Preferably, the first and second concentrating are independently performed under steam heating conditions;

The temperature of the first concentration and the second concentration are independently 70-90 ℃; the vacuum pressure of the first concentration and the second concentration is independently 0.02-0.05 MPa; the pressure of the first concentrated steam and the second concentrated steam is independently less than or equal to 0.06MPa.

The invention provides a preparation method of a health-care extract, which comprises the following steps:

mixing the Baoyuan decoction prepared by the preparation method of the technical scheme and the aqueous solution of dextrin, and concentrating to obtain the Baoyuan extract; the temperature of concentration is less than or equal to 90 ℃; the mass ratio of the dextrin to the Baoyuan decoction dry paste is (0.2-0.6): 1.

Preferably, the concentration is performed under steam heating;

the concentration temperature is 70-90 ℃; the vacuum pressure of the concentration is 0.02-0.05 MPa; the pressure of the concentrated steam is less than or equal to 0.06MPa.

The invention provides a preparation method of a health-care solid preparation, which comprises dry powder or granules, wherein the preparation method of the dry powder comprises the following steps: vacuum drying the primordial energy-preserving extract prepared by the preparation method of the technical scheme to obtain the primordial energy-preserving dry powder;

the preparation method of the granule comprises the following steps: and granulating the Baoyuan dry powder in a dry method to obtain the Baoyuan granule.

Preferably, the vacuum drying is vacuum belt drying; the working parameters of the vacuum belt drying include: the feeding temperature is 75-85 ℃; the feeding speed is 8-20L/h; the running speed of the crawler belt is 15+/-5 cm/min, the rotating speed of the distributing motor is 35-45 r/min, and the angle of the swing arm is 70-85 degrees; the heating temperature zone is as follows: one region 95.+ -. 5 ℃, two regions 96.+ -. 5 ℃ and three regions 96.+ -. 5 ℃; the vacuum degree is-0.10 to-0.09 MPa; the cooling temperature is 20-30 ℃;

the dry granulation is carried out in a granulator, and the working parameters of the dry granulation comprise: the pressure of the compression roller of the granulator is 14-18 MPa; the rotating speed of the compression roller of the granulator is 4-8 r/min; the vertical rotating speed of the screw feeder of the granulator is 22-28 r/min; the horizontal rotating speed of the screw feeder of the granulator is 110-130 r/min; the grain finishing speed is 110-140 r/min.

The invention provides the element-preserving solid preparation prepared by the preparation method, and the dry paste rate of the element-preserving solid preparation is 24-32%; the extract of the element-preserving solid preparation is 30-60%; the ginseng content of the element-preserving solid preparation is 4-9 mg/bag based on the total amount of ginsenoside Rg1 and ginsenoside Re; the astragalus content of the element-preserving solid preparation is 0.3-1.5 mg/bag calculated by astragaloside IV; the quality of 1 bag of the element-preserving solid preparation is 3.0g.

The invention provides a preparation method of Baoyuan decoction, which comprises the following steps: soaking the primordial qi-preserving decoction pieces in water to obtain primordial qi-preserving presoaked liquid; the primordial energy-preserving decoction pieces comprise ginseng decoction pieces, astragalus decoction pieces, cinnamon beverage, licorice beverage and ginger decoction pieces; the mass ratio of the water to the decoction pieces for keeping primordial energy is less than or equal to 14:1; performing first boiling extraction on the primordial preserving presoaked liquid to obtain first primordial water extract and primordial preserving dregs; mixing the residue and water, and boiling for extraction to obtain second extractive solution; the mass ratio of the water to the Baoyuan decoction pieces is less than or equal to 12:1; respectively carrying out first concentration and second concentration on the first and second water extract to obtain first and second concentrated solutions; and combining the first and second primordial energy-preserving concentrated solutions to obtain the primordial energy-preserving soup. The preparation method of the health care soup provided by the invention comprehensively tests water extraction and concentration: the step of reasonable design water extraction is to divide two steps of water extraction, and simultaneously, the water consumption in each step of water extraction is reasonably set, the water addition amount is reduced to be less than 14 times from nearly 36 times (the traditional water extraction amount of the Baoyuan decoction), and the extraction rate of active pharmaceutical ingredients is improved as much as possible on the premise of ensuring that the extraction effects of the Baoyuan decoction and the Baoyuan decoction reference sample are basically consistent; then, the water extracts of the elements obtained by the two steps of water extraction are respectively concentrated, compared with the traditional 'merging and concentrating', namely, the traditional Chinese patent medicine concentration is generally carried out after merging the extracted extracts of several times, the traditional merging and concentrating mode reduces the total concentration of the liquid medicine, prolongs the absolute heating and concentrating time of the liquid medicine, is unfavorable for heat-sensitive active medicine components, and adopts 'fractional concentration', so that the content of the active medicine components in the water extracts of the two steps is quickly higher on the basis that the water consumption of the water extraction step is greatly reduced, the total heated time of the active medicine components in the water extracts is further effectively reduced, the protection and the retention of the active medicine components in the element-preserving soup are facilitated, and the destruction of the active medicine components (such as heat-sensitive active components such as ginsenoside) due to high temperature is avoided. In conclusion, the preparation method provided by the invention ensures the consistency of the extraction effect of the Baoyuan decoction and the traditional Baoyuan decoction reference sample, and the obtained Baoyuan decoction has high content of effective active ingredients and good efficacy.

In the invention, the mass ratio of the water to the health-care decoction pieces is (8-14) 1; the soaking time is 30-60 min; the first boiling extraction comprises a heating stage heated by steam and a boiling heat preservation stage heated by steam; the pressure of steam in the heating stage is less than or equal to 0.2MPa; the heat preservation time of the boiling heat preservation stage is 40-50 min, and the pressure of steam of the boiling heat preservation stage is 0.02-0.08 MPa. Compared with the conventional traditional Chinese medicine extraction, the extraction time is usually 1-2 hours per time, and impurities such as fiber, starch and the like are often proposed, so that the effective active ingredients are not increased, and even the effective active ingredients are possibly damaged after long-time heating. Compared with the traditional extraction mode of excessive extraction and high energy consumption, the preparation method provided by the invention has the advantages of short extraction time and high extraction efficiency (higher extraction rate of ginsenoside) on the basis of moderate water addition amount in the first extraction, further improves the quality and efficacy of the Baoyuan decoction product and reduces the production cost.

In the invention, the mass ratio of the water to the Baoyuan decoction pieces is (6-12) 1; the second boiling extraction comprises a heating stage heated by steam and a boiling heat preservation stage heated by steam; the pressure of steam in the heating stage is less than or equal to 0.2MPa; the heat preservation time of the boiling heat preservation stage is 30-40 min, and the pressure of steam of the boiling heat preservation stage is 0.02-0.08 MPa. The invention further has the advantages of short extraction time and high extraction efficiency (higher extraction rate of ginsenoside) on the basis of moderate water addition amount in the second extraction, further improves the quality and the drug effect of the Baoyuan decoction product and reduces the production cost.

Further, in the present invention, the first concentration and the second concentration are independently performed under steam heating conditions; the temperature of the first concentration and the second concentration are independently 70-90 ℃; the vacuum pressure of the first concentration and the second concentration is independently 0.02-0.05 MPa; the vapor pressure of the first concentrate and the second concentrate are independently equal to or less than 0.06MPa. On the basis of fractional concentration, the invention adopts reduced pressure concentration, the temperature is controlled to be 70-90 ℃, and compared with the traditional normal pressure concentration mode, the invention can not only improve the evaporation efficiency, but also reduce the component damage. The concentration method provided by the invention reduces the destruction rate of index components (ginsenoside) from about 6% to 0%, and effectively solves the problem that index components of the Baoyuan decoction are destroyed seriously.

The invention provides a preparation method of a health-care extract, which comprises the following steps: mixing the Baoyuan decoction prepared by the preparation method of the technical scheme and the aqueous solution of dextrin, and concentrating to obtain the Baoyuan extract; the temperature of concentration is less than or equal to 90 ℃; the mass ratio of the dextrin to the Baoyuan decoction dry paste is (0.2-0.6): 1. According to the invention, the Baoyuan decoction and the dextrin aqueous solution are mixed before further concentration, the uniform mixing of auxiliary materials and liquid medicine is ensured through the further concentration process, and meanwhile, the dextrin is used as the medicinal auxiliary material, so that the loss of the Baoyuan decoction dry paste caused by the residues of the Baoyuan decoction with high viscosity in concentration equipment and pipelines can be effectively reduced.

The invention provides a preparation method of a health-care solid preparation, which comprises dry powder or granules, wherein the preparation method of the dry powder comprises the following steps: vacuum drying the primordial energy-preserving extract prepared by the preparation method of the technical scheme to obtain the primordial energy-preserving dry powder; the preparation method of the granule comprises the following steps: and granulating the Baoyuan dry powder in a dry method to obtain the Baoyuan granule. The preparation method provided by the invention adopts the element-preserving extract prepared by the preparation method as the raw material, and the dextrin in the element-preserving extract can effectively avoid the serious problem of dry extract loss caused by large bubbles (containing more saponins) and sticky tapes in the element-preserving extract drying process; meanwhile, the health care extract contains heat-sensitive components such as ginsenoside, and the traditional high-temperature drying and spray drying methods are easy to agglomerate and damage heat-sensitive effective components such as ginsenoside. The preparation method of the element-preserving solid preparation provided by the invention adopts a vacuum belt type drying mode, has the advantages of low drying temperature, short drying time, less loss, high efficiency and the like, and the obtained element-preserving solid preparation can not agglomerate and damage thermosensitive components such as ginsenoside and the like in the drying process, and has uniform distribution of each component in the element-preserving solid preparation, high content of effective components such as ginsenoside and the like and good efficacy.

The invention provides the element-preserving solid preparation prepared by the preparation method, and the dry paste rate of the element-preserving solid preparation is 24-32%; the extract of the element-preserving solid preparation is 30-60%; the ginseng content of the element-preserving solid preparation is 4-9 mg/bag based on the total amount of ginsenoside Rg1 and ginsenoside Re; the astragalus content of the element-preserving solid preparation is 0.3-1.5 mg/bag calculated by astragaloside IV; the quality of 1 bag of the element-preserving solid preparation is 3.0g. The quality standard of the Baoyuan solid preparation provided by the invention is consistent with that of a Baoyuan decoction reference sample, and the auxiliary material only contains dextrin, so that the Baoyuan solid preparation is simple and healthy, good in dissolubility, high in bioavailability, convenient to take and carry and better in stability compared with the traditional decoction.

Drawings

FIG. 1 is a process flow diagram of a Baoyuan granule;

FIG. 2 is a graph of HPLC control features of the guarantor granules;

FIG. 3 is a chart for investigating hygroscopicity of the Baoyuan decoction pieces in different humidity environments;

fig. 4 is a graph showing the loss of the pilot scale validation process of the Baoyuan granules.

Detailed Description

mixing the primordial qi-preserving medicine residues with water for second boiling extraction, wherein the mass ratio of the water to the primordial qi-preserving medicine residues is less than or equal to 12:1; obtaining a second water extract;

In the present invention, all raw material components are commercially available products well known to those skilled in the art unless specified otherwise.

The preparation method comprises the steps of soaking the element-preserving decoction pieces in water to obtain element-preserving presoaked liquid; the primordial energy-preserving decoction pieces comprise ginseng decoction pieces, astragalus decoction pieces, cinnamon decoction pieces, licorice decoction pieces and ginger decoction pieces; the mass ratio of the water to the decoction pieces for keeping the primordial energy is less than or equal to 14:1.

In the invention, the ginseng, the cinnamon and the ginger are preferably consistent with the basic sources in the Chinese pharmacopoeia of 2020 edition; the astragalus source is preferably astragalus mongholicus Astragalus Membranaceus (fishe.) bge.var.mongholicus (bge.) Hsiao of leguminous plants; the glycyrrhiza is preferably Glycyrrhiza uralensis Fisch.

In the invention, the mass ratio of the ginseng decoction pieces, the astragalus decoction pieces, the liquorice decoction pieces, the cinnamon decoction pieces and the ginger decoction pieces is preferably 373:746:186:75: (100-300).

In the invention, the processing method of the ginseng decoction pieces is preferably as follows: (1) selecting: selecting Ginseng radix raw materials, and selecting impurities and deterioration products, and grading the sizes (small grade: diameter of root middle part <1.5cm, large grade: diameter of root middle part not less than 1.5 cm). (2) Spray washing: and water spray washing for 10-15 min. (3) Moistening: and (3) at the temperature of 5-25 ℃, small-grade moistening is carried out for 18-24 hours, and large-grade moistening is carried out for 48-72 hours until the internal humidity and the external humidity are consistent. (4) Cutting: cutting into uniform thick slices of 2-4 mm. (5) And (3) drying: the thickness is 2-3 cm, the temperature is 60-70 ℃, and the drying is carried out for 4-5 h. (6) Fine selection: sieving with 3mm sieve, and manually picking out unqualified product.

In the invention, the processing method of the astragalus decoction pieces is preferably as follows: (1) selecting: and (5) taking the astragalus root raw medicinal material, and picking out impurities and modified products. (2) Spray washing: and water spray washing for 5-10 min. (3) Moistening: moistening for 18-24 h at 5-35 ℃. (4) Cutting: cutting into uniform thick slices of 2-4 mm. (5) And (3) drying: the thickness is 2-3 cm, the temperature is 70-80 ℃, and the drying is 3.5-4 h. (6) Fine selection: sieving with 3mm sieve, and manually picking out unqualified product.

In the invention, the processing method of the liquorice decoction pieces is preferably as follows: (1) selecting: selecting Glycyrrhrizae radix raw material, and selecting out impurities and deterioration products, and grading the size (small grade: root tip diameter <1.0cm, large grade: root tip diameter not less than 1.0 cm). (2) Spray washing: and water spray washing for 10-15 min. (3) Moistening: moistening at 5-25 deg.c for 3.5-18 hr. (4) Cutting: cutting into uniform thick slices of 2-4 mm. (5) And (3) drying: the thickness is 2-3 cm, the temperature is 60-70 ℃, and the drying is carried out for 4-5 h. (6) Fine selection: sieving with 3mm sieve, and manually picking out unqualified product.

In the invention, the processing method of the cinnamon decoction pieces is preferably as follows: (1) selecting: taking cinnamon raw material, removing impurities, and scraping coarse skin. (2) Cutting: cut into blocks of 15mm width.

In the invention, the processing method of the ginger decoction pieces is preferably as follows: (1) selecting: removing impurities and cleaning. (2) Cutting: cutting into uniform thick slices of 2-4 mm when in use.

In the present invention, the soaking is preferably performed in an extraction tank.

In the invention, the mass ratio of the water to the decoction pieces for keeping the elements is less than or equal to 14:1, preferably (8-14): 1, and more preferably 10:1 during soaking.

In the present invention, the soaking temperature is preferably room temperature.

In the present invention, the soaking time is 30 to 60 minutes, more preferably 50 minutes.

After the element-preserving pre-soaking liquid is obtained, the element-preserving pre-soaking liquid is subjected to first boiling extraction to obtain a first element-preserving water extract and element-preserving medicine residues.

In the present invention, the specific implementation process of the first boiling extraction preferably includes: and (3) opening a steam valve of the extraction tank, heating by heating steam, opening an external circulation of the extraction tank when the temperature reaches 90 ℃, starting timing when the temperature reaches boiling, keeping the pressure of the heating steam stable, performing the first boiling extraction, closing the external circulation after the first boiling extraction is finished, and discharging the liquid medicine to obtain the first water extract and the residue.

In the present invention, the first boiling extraction preferably includes a warm-up phase heated by steam and a boiling hold phase heated by steam.

In the present invention, the pressure of the steam in the temperature rising stage is preferably 0.2MPa or less.

In the present invention, the holding time of the boiling holding stage is preferably 40 to 50 minutes, more preferably 45 minutes.

In the present invention, the pressure of the steam in the boiling and heat-preserving stage is preferably 0.02 to 0.08MPa, more preferably 0.05 to 0.08MPa.

In the present invention, after the first boiling extraction is completed, the first liquid medicine obtained by the first boiling extraction is preferably subjected to post-treatment to obtain the first water extract of the first principal component. In the present invention, the post-treatment preferably includes: and filtering the first liquid medicine, and then carrying out centrifugal separation to obtain a liquid component, and carrying out fine filtration to obtain the first primary water extract. In the present invention, the filtration is preferably 120 mesh filtration. The centrifugation is preferably carried out in a centrifuge, the separation speed of the centrifugation is preferably 80L/min, and the centrifugation time is preferably once every 20min for deslagging. In the present invention, the fine filtration is preferably performed by a plate-and-frame filter having a membrane pore size of preferably 5 to 15 μm.

In the invention, the relative density of the first primary water extract is more than or equal to 1.010. The relative density of the first primary water extract is the relative density under the condition of 20 ℃. In the present invention, the relative density of the first aqueous extract is the density relative to water.

After the element-preserving medicine residue is obtained, the element-preserving medicine residue and water are mixed for second boiling extraction to obtain a second element-preserving water extract; the mass ratio of the water to the Baoyuan decoction pieces is less than or equal to 12:1.

In the present invention, the mass ratio of the water to the residue during the second boiling extraction is preferably (6 to 12): 1, more preferably (7 to 8): 1.

In the present invention, the specific implementation process of the second boiling extraction preferably includes: and (3) opening a steam valve of the extraction tank, heating by heating steam, opening an external circulation of the extraction tank when the temperature reaches 90 ℃, starting timing when the temperature reaches boiling, keeping the pressure of the heating steam stable, performing second boiling extraction, closing the external circulation after the second boiling extraction is finished, and discharging the liquid medicine to obtain the second water extract with the primary retention.

In the present invention, the second boiling extraction preferably includes a warm-up phase heated by steam and a boiling hold phase heated by steam.

In the present invention, the holding time of the boiling holding stage is preferably 30 to 40 minutes, more preferably 35 minutes.

In the present invention, after the second boiling extraction is completed, the second medicinal liquid obtained by the second boiling extraction is preferably subjected to post-treatment to obtain the second water extract. In the present invention, the post-treatment preferably includes: and filtering the second liquid medicine, and then carrying out centrifugal separation to obtain a liquid component, and carrying out fine filtration to obtain the second water extract with the element keeping function. In the present invention, the filtration is preferably 120 mesh filtration. The centrifugation is preferably carried out in a centrifuge, the separation speed of the centrifugation is preferably 80L/min, and the centrifugation time is preferably once every 20 minutes. In the present invention, the fine filtration is preferably performed by a plate-and-frame filter having a membrane pore size of preferably 5 to 15 μm.

In the invention, the relative density of the second water extract is more than or equal to 1.002. The relative density of the second water extract is that of the second water extract at 20 ℃. In the present invention, the relative density of the second water extract is the density relative to water.

After the first and second water-retaining extracts are obtained, the first and second water-retaining extracts are respectively subjected to first and second concentration to obtain first and second concentrated solutions.

In the present invention, the first concentration is preferably performed under steam heating. In the present invention, the temperature of the first concentration is preferably 70 to 90 ℃, more preferably 80 to 90 ℃, and most preferably 85 ℃; the vacuum pressure of the first concentration is preferably 0.02 to 0.05MPa, more preferably 0.04 to 0.05MPa; the heating steam pressure of the first concentration is preferably not more than 0.09MPa, more preferably 0.04 to 0.09MPa.

In the present invention, the relative density of the first primary care concentrate is preferably 1.10 or more. The relative density of the first primary concentrate is that at 20 ℃. In the present invention, the relative density of the first primary concentrate is the density relative to water.

In the present invention, the second concentration is preferably performed under steam heating. In the present invention, the temperature of the second concentration is preferably 70 to 90 ℃, more preferably 80 to 90 ℃, and most preferably 85 ℃; the vacuum pressure of the second concentration is preferably 0.02 to 0.05MPa, more preferably 0.04 to 0.05MPa; the heating steam pressure of the second concentration is preferably not more than 0.09MPa, more preferably 0.04 to 0.09MPa.

In the present invention, the relative density of the second health care concentrated solution is preferably not less than 1.10. The relative density of the second health-care concentrated solution is the relative density under the condition of 20 ℃. In the present invention, the relative density of the second guaranteed concentrate is the density relative to water.

After the first and second primordial-energy-preserving concentrated solutions are obtained, the first and second primordial-energy-preserving concentrated solutions are combined to obtain the primordial-energy-preserving soup.

In the invention, the Baoyuan soup is preferably stored in a liquid storage tank or a turnover barrel for standby.

The invention provides the Baoyuan decoction prepared by the preparation method of the technical scheme, and the relative density of the Baoyuan decoction is more than or equal to 1.10. The relative density of the Baoyuan decoction is the relative density under the condition of 20 ℃. In the present invention, the relative density of the Baoyuan decoction is the density relative to water.

In the invention, the mass percentage of the ginsenoside in the health care decoction is preferably more than or equal to 0.45 percent based on the total amount of the ginsenoside Rg1 and the ginsenoside Re.

The invention provides a preparation method of a health-care extract, which comprises the following steps: mixing the Baoyuan decoction prepared by the preparation method of the technical scheme and the aqueous solution of dextrin, and concentrating (hereinafter referred to as third concentration) to obtain the Baoyuan extract; the temperature of the third concentration is less than or equal to 90 ℃; the mass ratio of the dextrin to the Baoyuan decoction dry paste is (0.2-0.6): 1.

In the present invention, the mass ratio of the dextrin to water in the aqueous solution of the dextrin is preferably 1 (2 to 6), more preferably 1 (2.5 to 5).

In the present invention, the third concentration is preferably performed in a single-effect concentrator.

In the present invention, the third concentration is preferably performed under steam heating. In the present invention, the temperature of the third concentration is preferably 70 to 90 ℃, more preferably 80 to 90 ℃, and most preferably 85 ℃; the vacuum pressure of the third concentration is preferably 0.04 to 0.07MPa, more preferably 0.04 to 0.06MPa; the heating steam pressure of the third concentration is preferably not more than 0.09MPa, more preferably 0.04 to 0.09MPa.

In the invention, the relative density of the element-preserving extract is preferably 1.25-1.36. The relative density of the Baoyuan extract is the relative density under the condition of 20 ℃. In the invention, the relative density of the element-preserving extract is the density relative to water.

The invention provides the primordial qi-preserving extract prepared by the preparation method.

In the invention, based on the total amount of ginsenoside Rg1 and ginsenoside Re, the conversion of the ginsenoside in the prebiotic extract into the ginseng decoction pieces is more than or equal to 0.25 percent by mass.

In the present invention, the vacuum drying is preferably vacuum belt drying; the operating parameters of the vacuum belt drying preferably include: the feeding temperature is preferably 75-85 ℃, more preferably 75-83 ℃; the feeding rate is preferably 8 to 20L/h, more preferably 12 to 16L/h; the track running speed is preferably 15+/-5 cm/min, more preferably 15-16 cm/min; the rotating speed of the cloth motor is preferably 40r/min, the swing arm angle is preferably 70-85 degrees, and more preferably 75-80 degrees; the heating temperature zone is preferably: one region 95.+ -. 5 ℃, two regions 96.+ -. 5 ℃ and three regions 96.+ -. 5 ℃; the vacuum degree is preferably-0.10 to-0.09 MPa; the cooling temperature is preferably 20 to 30 ℃.

In the present invention, the dry granulation is preferably performed using a granulator, and the operating parameters of the dry granulation preferably include: the pressure of the compression roller of the granulator is preferably 14-18 MPa, more preferably 15-18 MPa; the vertical rotation speed of the screw feeder is preferably 22-28 r/min, more preferably 24-28 r/min, and the horizontal rotation speed of the screw feeder is preferably 110-130 r/min, more preferably 115-125 r/min; the rotation speed of the press roller is preferably 4-8 r/min, more preferably 5-8 r/min; the particle-sizing speed is preferably 110 to 140r/min, more preferably 130 to 140r/min. In the specific embodiment of the invention, during the granulation process, the condition of the granulator is preferably observed (for example, if the raw materials in a hopper are sufficient or not, the raw materials should be added in time when the raw materials are insufficient).

In the present invention, the mass ratio of the dextrin to the dry extract of the Baoyuan decoction is preferably (0.2 to 0.6): 1, more preferably (0.3 to 0.5): 1, when the Baoyuan extract and the Baoyuan solid preparation are prepared.

In the invention, the Baoyuan decoction dry paste is the dry weight of solid matters remained after the Baoyuan decoction is completely dried.

In the invention, the dry paste rate of the element-preserving solid preparation is preferably 24-32%.

In the present invention, the extract of the metachromatic solid preparation is preferably 30 to 60%.

In the invention, the ginseng content of the element-preserving solid preparation is 4-9 mg/bag based on the total amount of ginsenoside Rg1 and ginsenoside Re.

In the invention, the astragalus content of the element-preserving solid preparation is 0.3-1.5 mg/bag calculated by astragaloside IV.

In the present invention, the specification of the meta-solid preparation is preferably 3.0 g/bag.

In the present invention, the meta-protection granule is preferably packaged using a pharmaceutical composite film.

The element-protecting granule provided by the invention is a yellowish-brown to yellowish-brown granule; light smell, slightly bitter and slightly spicy.

In the present invention, the identification method of the meta-particle preferably includes the steps of:

taking 2g of Baoyuan granule powder, adding 50mL of 50% ethanol, carrying out ultrasonic treatment for 40 minutes, cooling, filtering, evaporating the filtrate to dryness, dissolving residues by using 20mL of water, extracting by shaking with water saturated n-butanol for 2 times, each time by 25mL, combining n-butanol solutions, washing with ammonia test solution for 2 times, each time by 20mL, discarding the ammonia test solution, evaporating the n-butanol solution to dryness, and dissolving residues by adding 1mL of methanol to obtain a test solution. And preparing a pair of medicinal material solutions by respectively preparing 2g of astragalus control medicinal material and 1g of ginseng control medicinal material in the same way. According to the thin layer chromatography (general rule 0502), 1-2 mu L of each of the three solutions is absorbed and respectively spotted on the same silica gel G thin layer plate. Taking an upper layer solution of n-butanol-ethyl acetate-water (4:1:5) as a developing agent, developing, taking out, airing, spraying 10% sulfuric acid ethanol solution, heating at 105 ℃ until the color of spots is clear, and respectively placing the spots under sunlight and an ultraviolet lamp (365 nm) for inspection. In the chromatogram of the test sample, spots with the same color appear at the corresponding positions of the chromatogram of the control medicinal material.

(2) Taking 2g of Baoyuan granule powder, adding 50mL of 50% ethanol, ultrasonically extracting for 40 min, filtering, evaporating the filtrate to dryness, adding 20mL of water into the residue to dissolve, extracting with water-saturated n-butanol for 2 times, each time 25mL, combining n-butanol solutions, evaporating to dryness on a water bath, and adding 1mL of methanol into the residue to dissolve to obtain a sample solution. And 1g of licorice reference medicine is prepared, and a reference medicine solution is prepared by the same method. The two solutions were each drawn 1-2. Mu.L and spotted on the same silica gel G thin layer plate prepared with 1% sodium hydroxide solution, respectively, according to a thin layer chromatography (general rule 0502) test. Using ethyl acetate-formic acid-glacial acetic acid-water (15:1:1:2) as developing agent, developing, taking out, air drying, spraying 10% sulfuric acid ethanol solution, heating at 105deg.C until the color of spots is clear, and respectively placing under sunlight and ultraviolet lamp (365 nm) for inspection. In the chromatogram of the test sample, spots with the same color appear at the corresponding positions of the control medicinal materials.

(3) Taking 6g of Baoyuan decoction granules, adding 10mL of water, adding 30mL of absolute ethyl alcohol, carrying out ultrasonic treatment for 30 minutes, filtering, evaporating filtrate, extracting residues with n-hexane twice, each time for 30mL, combining n-hexane liquid, evaporating at 50 ℃ to dryness, and adding 1mL of n-hexane into residues to dissolve to obtain a sample solution. 2g of ginger medicinal material is taken, 30mL of water is added, and the mixture is decocted for 30 minutes and filtered. Extracting the filtrate with n-hexane twice (30 mL each time), mixing n-hexane solutions, evaporating to dryness at 50deg.C, and dissolving the residue with n-hexane 1mL to obtain control medicinal material solution. Taking 6-gingerol solution, adding methanol to prepare 1mg solution per 1mL to obtain reference solution. Sucking 2 mu L of each of the control medicinal material and the control substance solution, and 5 mu L of the test substance solution, respectively spotting on the same silica gel G thin layer plate, and using petroleum ether (60-90 ℃): ethyl acetate (2:1) is used as developing agent, developed, taken out, dried, sprayed with 5% vanillin sulfuric acid test solution, heated at 105 ℃ until the spots develop clearly, and inspected under sunlight.

The invention also provides the quality control standard of the Baoyuan solid preparation, which comprises an HPLC characteristic spectrum, characteristic component content, extract content and dry extract rate of the Baoyuan solid preparation;

the characteristic component content comprises: the ginseng content of the element-preserving solid preparation is 4.0-9.0 mg bags based on the total amount of ginsenoside Rg1 and ginsenoside Re; the astragalus content of the element-preserving solid preparation is 0.30-1.5 mg/bag calculated by astragaloside IV;

the extract is 30-60%;

the dry paste rate is 24-32%;

the quality of 1 bag of the element-preserving solid preparation is 3.0g.

In the invention, the dry paste rate of the Baoyuan granule is measured according to a moisture measurement method (the general rule 0832 of the year 2020 edition of Chinese pharmacopoeia).

In the invention, the method for measuring the extract of the element-preserving granule comprises the following steps: grinding the product, weighing about 2g, precisely weighing, precisely adding 100mL of ethanol, and measuring by hot dipping under the condition of alcohol-soluble extract measurement method (general rule 2201 in the year 2020 of Chinese pharmacopoeia).

In the method for obtaining the HPLC characteristic spectrum of the element-preserving granule, the method is preferably measured by referring to high performance liquid chromatography (general rule 0512 in the year 2020 of Chinese pharmacopoeia).

In the invention, the obtaining of the HPLC characteristic spectrum of the element-preserving granule preferably takes octadecylsilane chemically bonded silica gel as a filler; acetonitrile as mobile phase A and water as mobile phase B, and performing gradient elution according to the specification in Table 1; the detection wavelength is 203nm; the column temperature was 35 ℃. The theoretical plate number is not less than 6000 calculated according to ginsenoside Rb1 peak.

TABLE 1 gradient elution procedure

Time (minutes)	Mobile phase a (%)	Mobile phase B (%)
			0～20	16→17	84→83
20～35	17→18	83→82
			35～55	18→25.5	82→74.5
55～75	25.5→29	74→71
			75～110	29→42	71→58

In the invention, when the HPLC characteristic spectrum of the element-preserving granule is obtained, the preparation method of the reference substance solution is preferably as follows: taking appropriate amounts of ginsenoside Rg1 reference, ginsenoside Re reference and ginsenoside Rb1 reference, precisely weighing, and adding methanol to obtain a mixed solution containing ginsenoside Rg10.20mg, ginsenoside Re 0.20mg and ginsenoside Rb10.20mg in lmL.

In the invention, when the HPLC characteristic spectrum of the element-preserving granule is obtained, the preparation method of the sample solution is preferably as follows: taking about 1.5g of the element-preserving granule powder, precisely weighing, placing the powder into a 100mL conical flask with a plug, precisely adding 50mL of 50% ethanol, weighing, ultrasonically treating (800W, 40 kHz) for 30 minutes, cooling, weighing again, adding 50% ethanol to supplement the lost weight, filtering, precisely weighing 50mL of the subsequent filtrate, recovering the solvent until dryness, adding 15mL of water into the residue to dissolve the residue, extracting the residue by shaking with water saturated n-butanol for 4 times, each 25mL, combining n-butanol extract, washing the residue with ammonia test solution for 3 times, each 20mL, discarding the ammonia test solution, recovering the solvent from the n-butanol solution until dryness, adding a proper amount of 80% methanol into the residue to dissolve the residue, transferring the residue into a 5mL measuring flask, adding 80% methanol to a scale, shaking uniformly, and filtering to obtain the element-preserving granule.

In the invention, when the HPLC characteristic spectrum of the element-preserving granule is obtained, the determination method is preferably as follows: precisely sucking 10 μl of each of the control solution and the sample solution, and injecting into a liquid chromatograph for measurement.

In the invention, 11 characteristic peaks should be presented in the characteristic spectrum of the sample, wherein 3 peaks should be consistent with the corresponding reference peak retention time, the peak corresponding to the ginsenoside Rb1 reference peak is S peak (peak 9), and the relative retention time of each characteristic peak and S peak is calculated and is within +/-5% of the specified value. The specified value is: 0.38 (Peak 1), 0.53 (Peak 2), 0.58 (Peak 3), 0.59 (Peak 4), 0.60 (Peak 5), 0.84 (Peak 6), 0.88 (Peak 7), 0.96 (Peak 8), 1.00 (Peak 9), 1.24 (Peak 10), 1.26 (Peak 11), and the control characteristic map is shown in FIG. 2. In fig. 2, peak 3: ginsenoside Rg1; peak 4: ginsenoside Re; peak 9: ginsenoside Rb1 (reference peak); peak 1 is from Glycyrrhiza glabra; peak 2, 5 are from Astragalus membranaceus; peaks 3, 4, 8, 9 are from ginseng.

In the invention, the ginseng content determination of the element-preserving granules is preferably determined according to high performance liquid chromatography (general rule 0512).

The chromatographic conditions are the same as the HPLC characteristic spectrum of the Baoyuan granule;

The preparation of the reference substance solution is the same as the HPLC characteristic spectrum of the Baoyuan granule

The preparation of the sample solution is the same as the HPLC characteristic spectrum of the Baoyuan granule;

the measurement method is preferably as follows: precisely sucking 10 μl of each of the control solution and the sample solution, and injecting into a liquid chromatograph for measurement.

In the invention, the astragaloside IV determination of the element-preserving granules is preferably determined according to high performance liquid chromatography (the general rule 0512 of the year 2020 edition of Chinese pharmacopoeia).

The chromatographic conditions preferably use octadecylsilane chemically bonded silica as a filler; isocratic elution with acetonitrile-water (v: v=34:66); the flow rate is 1.0ml/min; the detector is an ELSD; the column temperature was 30deg.C, the drift tube temperature was 70deg.C, the atomizer temperature was 60deg.C (100%), and the gas pressure was 20psi. The theoretical plate number should be not less than 5000 calculated according to astragaloside IV peak.

The preparation of the reference substance solution is preferably as follows: taking appropriate amount of astragaloside IV reference substance, precisely weighing, and adding 80% methanol solution to obtain solution containing 20ug of astragaloside IV per 1 ml.

The preparation of the test solution is the same as the HPLC characteristic spectrum of the Baoyuan granule.

The measurement method is preferably as follows: respectively accurate reference solution 5 μl (or 10 μl), and sample solution 20 μl, and liquid chromatograph for measurement.

The vitality-preserving granule provided by the invention has the effects of tonifying qi and warming yang, and is mainly used for treating deficiency of vital qi. Primordial qi deficiency, listlessness, muscle weakness, poor appetite, complexionWhite, calm and calm, no top of acne, insufficient pulp and mixed symptoms, all of which are weak, are suitable for taking.

The element-protecting granule provided by the invention is taken after being mixed with boiled water. 1 bag at a time and 2 times a day.

The specification of the element-protecting granule provided by the invention is 3.0g per bag.

The storage method of the element-preserving granule provided by the invention is sealing.

The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

In the examples and comparative examples of the present invention:

film-drinking base: the ginseng, the cinnamon and the ginger are consistent with the radix source in Chinese pharmacopoeia of 2020 edition, and the radix astragali source is Mongolian radix astragali Astragalus Membranaceus (Fisch.) Bge.var.Mongholicus (Bge.) Hsiao of leguminous plants; the Glycyrrhiza uralensis is a Glycyrrhiza uralensis Glycyrrhiza uralensis Fisch.

Each traditional Chinese medicine is processed before use:

the processing method of the ginseng decoction pieces comprises the following steps: (1) selecting: selecting Ginseng radix raw materials, and selecting impurities and deterioration products, and grading the sizes (small grade: diameter of root middle part <1.5cm, large grade: diameter of root middle part not less than 1.5 cm). (2) Spray washing: and water spray washing for 10-15 min. (3) Moistening: and (3) at the temperature of 5-25 ℃, small-grade moistening is carried out for 18-24 hours, and large-grade moistening is carried out for 48-72 hours until the internal humidity and the external humidity are consistent. (4) Cutting: cutting into uniform thick slices of 2-4 mm. (5) And (3) drying: the thickness is 2-3 cm, the temperature is 60-70 ℃, and the drying is carried out for 4-5 h. (6) Fine selection: sieving with 3mm sieve, and manually picking out unqualified product.

The processing method of the astragalus decoction pieces comprises the following steps: (1) selecting: and (5) taking the astragalus root raw medicinal material, and picking out impurities and modified products. (2) Spray washing: and water spray washing for 5-10 min. (3) Moistening: moistening for 18-24 h at 5-35 ℃. (4) Cutting: cutting into uniform thick slices of 2-4 mm. (5) And (3) drying: the thickness is 2-3 cm, the temperature is 70-80 ℃, and the drying is 3.5-4 h. (6) Fine selection: sieving with 3mm sieve, and manually picking out unqualified product.

The processing method of the liquorice decoction pieces comprises the following steps: (1) selecting: selecting Glycyrrhrizae radix raw material, and selecting out impurities and deterioration products, and grading the size (small grade: root tip diameter <1.0cm, large grade: root tip diameter not less than 1.0 cm). (2) Spray washing: and water spray washing for 10-15 min. (3) Moistening: moistening at 5-25 deg.c for 3.5-18 hr. (4) Cutting: cutting into uniform thick slices of 2-4 mm. (5) And (3) drying: the thickness is 2-3 cm, the temperature is 60-70 ℃, and the drying is carried out for 4-5 h. (6) Fine selection: sieving with 3mm sieve, and manually picking out unqualified product.

The processing method of the ginger decoction pieces comprises the following steps: removing impurities and cleaning. When in use, the thick slices are cut.

Example 1

Prescription of Baoyuan granule: 710g of ginseng, 1420g of astragalus, 354g of liquorice, 143g of cinnamon and 571g of ginger;

according to the flow path shown in fig. 1: the preparation method of the Baoyuan granule comprises the following steps: adding Ginseng radix decoction pieces, radix astragali decoction pieces, cortex Cinnamomi decoction pieces, glycyrrhrizae radix decoction pieces, and rhizoma Zingiberis recens decoction pieces into an extraction tank, adding 10 times of water, and soaking for 50min; opening a steam valve of an extraction tank, heating by heating steam pressure less than or equal to 0.20MPa, opening an external circulation when the temperature reaches 90 ℃, starting timing when the temperature reaches boiling, stabilizing the steam pressure at 0.05-0.08 MPa, keeping for 45min, closing the external circulation (one decoction), discharging the first-time liquid medicine to obtain element-preserving slag, pumping the first-time liquid medicine into a separator for separation by a pump of a 120-mesh filter, controlling the separation speed at 80L/min, discharging slag once every 20min, and filtering the centrifugate of each time by a plate-frame filter (the aperture of a filter membrane is 5-15 mu m) to obtain a first-time element-preserving water extract; the relative density is more than or equal to 1.010;

adding water with the mass of 8 times of the medicinal materials into the residue of the element preservation, heating by heating steam pressure of less than or equal to 0.20MPa, opening external circulation when the temperature reaches 90 ℃, starting timing when the temperature reaches boiling, stabilizing the steam pressure at 0.05-0.08 MPa, keeping for 35min, closing external circulation (secondary decoction), discharging liquid medicine of the secondary decoction, pumping the liquid medicine of the secondary decoction into a separator for separation by a pump of a 120-mesh filter, controlling the separation speed at 80L/min, discharging slag once every 20min, respectively passing centrifugate of each time through a plate-frame filter (the aperture of a filter membrane is 5-15 mu m), and filtering to obtain a second water extract of the element preservation; the relative density is more than or equal to 1.002;

Respectively sucking the first and second water extracts into a pressure-reducing concentrator, opening a steam valve, starting heating, controlling the temperature at 70-90 ℃, controlling the vacuum pressure at 0.04-0.06 MPa, observing the boiling condition and the temperature at any time, regulating the vacuum pressure and the steam pressure, and respectively concentrating to obtain the first water extract with the relative density of more than or equal to 1.10; and the second element-preserving concentrated solution is pumped into a liquid storage tank for merging to obtain element-preserving soup, and weighing is carried out for later use.

384g of dextrin is weighed, the dextrin is poured into a stainless steel barrel, water which is 2 to 6 times of the mass of the dextrin is added, and the mixture is stirred to be completely dissolved, so as to obtain a dextrin aqueous solution for standby.

Starting vacuum, sucking dextrin aqueous solution and Baoyuan decoction aqueous extract into a single-effect concentrator, continuously concentrating until the relative density is 1.25-1.36 (20 ℃), pumping into a turnover barrel, and weighing for later use.

Starting a vacuum belt dryer, drying and pulverizing the element-preserving extract, wherein the working parameters of the vacuum belt dryer are as follows: the feeding temperature is 75-85 ℃; the feeding speed is 8-20L/h; the running speed of the crawler belt is 15+/-5 cm/min, the rotating speed of the distributing motor is 35-45 r/min, and the angle of the swing arm is 70-85 degrees; the heating temperature zone is as follows: one region 95.+ -. 5 ℃, two regions 96.+ -. 5 ℃ and three regions 96.+ -. 5 ℃; the vacuum degree is-0.10 to-0.09 MPa; the cooling temperature is 20-30 ℃; obtaining the Baoyuan dry powder.

The vacuum belt is dried to obtain the element-preserving dry powder, the element-preserving dry powder is placed in a hopper, the pressure of a compression roller of a granulator is regulated to be 14-18 MPa, and the rotating speed of a screw feeder is as follows: the vertical rotating speed is 22-28 r/min, the horizontal rotating speed is 110-130 r/min, the rotating speed of the press roller is 4-8 r/min, the finishing speed is 110-140 r/min, and dry granulation operation is carried out. In the running process, whether the raw materials in the hopper are sufficient or not is checked, and the raw materials should be added in time when the raw materials are insufficient. Making into 1000g granule, and packaging with pharmaceutical composite film according to 3.5 g/bag to obtain granule.

Example 2

Preparation process research of Baoyuan granule

1 extraction Process study

1.1 investigation of the Water addition quantity

Adopts a 2L round bottom flask and adopts a heating reflux extraction mode, so that different water adding times are respectively examined, and the decoction time is one decoction for 45 minutes and two decoction times for 35 minutes. The dry extract rate, the content of ginsenoside Rg1+Re and the transfer rate are taken as investigation indexes, and the detection results are shown in Table 2.

Table 2 statistical table of water-adding amount test results of Baoyuan decoction

Table 1 the results show that: the dry paste rate slightly increases with the increase of the water addition amount, but the dry paste rate of 10 times, 14 times and 16 times of the water addition amount and the total amount of ginsenoside Rg1+Re have no significant difference (RSD% < 5.0), and the transfer rate is higher than 90%, which indicates that the water addition amount of 10 times of the first decoction is enough, the water addition amount is not significant, the energy consumption is increased, and the efficiency is reduced, so that the first decoction water addition amount of the Baozi decoction preparation is determined to be 10 times of the decoction piece amount, and the second decoction water addition amount is determined to be 8 times of the decoction piece amount (the water addition amount of the first decoction minus the water absorption amount of the decoction piece).

1.2 investigation of the number of extractions

Adopting a 2L round bottom flask, heating and reflux extracting, wherein the first decoction is decocted with 10 times of water for 45 minutes, the second decoction is decocted with 8 times of water for 35 minutes, and the third decoction is decocted with 8 times of water for 35 minutes. The dry extract rate, the total content of ginsenoside Rg1+Re and the transfer rate are taken as investigation indexes, and the detection results are shown in Table 3.

Table 3 statistical table of test results of decoction times of Baoyuan decoction

Test stage	Dry paste rate (%)	Rg1+Re(％)	Transfer Rate (%)
				One decoction	23.55	0.332	84.7
Two-step decoction	6.36	0.043	11.0
				Three-decoction	2.62	0.013	3.3
One decoction and two decoction	29.91	0.375	95.7

The results in table 3 show: the third decoction dry extract rate and the total content of ginsenoside Rg1+Re are respectively increased by 2.6 percent and 0.01 percent. The meaning of increasing the times of one decoction is not great, and the effective components extracted twice are basically extracted completely. The number of extractions was thus determined to be 2.

1.3 extraction time investigation

The test uses a 2L round bottom flask and a heating reflux extraction mode. The first decoction is added with 10 times of water, and the second decoction is added with 8 times of water for different times. The dry extract rate, the total content of ginsenoside Rg1+Re and the transfer rate are taken as investigation indexes, and the detection results are shown in Table 4.

Table 4 statistical table of test results of decoction time of Baoyuan decoction

The results in table 4 show: the dry extract rate can be increased by prolonging the decoction time, but certain damage is caused to index components. Therefore, the decoction time is determined as one decoction for 45min and two decoction for 35min.

1.4 amplification experiments of extraction Process

3 batches of amplification verification tests are carried out by adopting a 100L extraction and concentration integrated machine so as to determine the stability of an extraction process. The test uses 2 times of prescription amount, one decoction is 10 times of water for 45 minutes, and two decoction is 8 times of water for 35 minutes. The dry extract rate, the total content of ginsenoside Rg1+Re and the transfer rate are taken as investigation indexes, and the statistics of detection results are shown in Table 5.

Table 5 statistical table of the results of the validation test of the extraction process of Baoyuan decoction

The results in table 5 show: the amplification verification test of 3 batches of extraction processes shows that the dry paste rate and the total content RSD% of ginsenoside Rg1+Re are less than 5, and the determined extraction process is stable.

2 research on concentration Process

2.1 reduced pressure concentration temperature and time investigation

About 1000g of Baoyuan decoction extract is taken, put into a rotary evaporator, concentrated for different times at 70 ℃ and 80 ℃ and 90 ℃ respectively (the production temperature is 70-90 ℃ in common use), and the damage condition of ginsenoside Rg1+Re is analyzed. The experimental results are shown in Table 6.

TABLE 6 reduced pressure concentration temperature and time investigation results

The results in table 6 show: the ginsenoside Rg1+Re is concentrated for 4 hours under reduced pressure at 70-90 ℃ (the common production temperature range), the ginsenoside Rg1+Re is not damaged obviously, the concentration is carried out for 5 hours, and the damage is about 4%, which indicates that the damage rule of the ginsenoside Rg1+Re is long-term damage at low temperature.

2.2 high temperature sterilization time investigation

Taking the concentrated solution of the Baoyuan decoction, placing the concentrated solution into a high-temperature sterilizer, and sterilizing at 105 ℃ for 40min and 60min respectively, wherein the detection results of index component change before and after sterilization are shown in Table 7.

TABLE 7 results of high temperature sterilization time investigation

The results in table 7 show: the sterilization at 105 ℃ for 40 minutes is not different from the sterilization at 60 minutes, the index components of the process cause certain damage, and the damage rate of the converted components of the extracting solution is about 6 percent. To ensure the sterilization effect, the sterilization time was set to 60 minutes.

3 study of drying Process

3.1 screening of auxiliary Material types and usage

Taking Baoyuan decoction concentrated solution, respectively adding 20% lactose, 20% soluble starch and 20%, 40% and 60% dextrin by weight of the Baoyuan decoction concentrated solution dry paste, and examining the influence of different auxiliary material types and dosage on the dry process and the dry powder material property. The detection results are shown in Table 8.

TABLE 8 statistical table of screening results for auxiliary materials

The results in table 8 show: (1) the 20% dextrin improves the foaming phenomenon in the process of drying, and the flowability of the dry powder is good (the subsequent granulation is facilitated); the improvement of the dry process was not evident with 20% soluble starch and 20% lactose and the flowability of the dry powder was poor.

(2) With the increase of the adding amount of the dextrin, the smoothness of the drying process is improved, but the solubility of the dried powder and the clarity of the solution are reduced. Comprehensively considering that the adding amount of 40% of dextrin has a smooth drying process and relatively good flowability and dissolubility of the dried powder.

3.2 investigation of the relative Density Range

The concentrated solution of Baoyuan decoction is taken, 40% of dextrin is added according to the conversion of the dry paste rate to prepare the liquid medicine with different relative densities before drying, the phenomenon of the drying process is examined, and the result is shown in Table 9.

Table 9 statistics of different relative density observations

3.3 investigation of hygroscopicity with Dry powder

In order to determine the humidity requirement of workshop production environment and the longest storage time from the dry powder carrying to the completion of granulation, the study carried out the hygroscopicity investigation of the pure powder of Baoyuan decoction (without adding auxiliary materials) and the dry powder of 40% dextrin carrying for 30 hours continuously. Firstly, sulfuric acid with different concentrations is adopted for establishing 30%, 50% and 70% humidity environments, samples are dried to constant weight and then placed in different humidity environments, the samples are weighed at 1h, 2h, 4h, 6h, 8h, 10h, 22h and 30h respectively from the beginning of placing, and the moisture absorption rate (moisture absorption rate=water absorption rate/constant weight sample weight) is calculated. The moisture absorption examination results of the Baoyuan decoction with dry powder are shown in Table 10 and FIG. 3.

Table 10 moisture absorption survey table of Baoyuan decoction with dry powder

The results show that: (1) the moisture absorption rate of different dry powders in different humidity environments is greatly different, and the higher the ambient humidity is, the higher the moisture absorption rate of a sample is in the same time; under the same condition, the moisture absorption rate of the pure powder is more than 40 percent of the dry powder of the dextrin belt; (2) under the environment of 29.5% humidity, the pure powder and 40% dextrin with dry powder are placed for 30 hours, the moisture absorption rates are 3.11% and 2.14% respectively, and the moisture absorption rate is low; under the environment of 66.7% humidity, the pure powder and 40% dextrin with dry powder absorb water more rapidly, so that the sample is prevented from being exposed in the high humidity environment; the dry powder is placed for 10 hours under the environment with 49.7 percent of humidity, and the moisture absorption rates of the pure powder and the dry powder with 40 percent of dextrin are respectively 5.21 percent and 4.42 percent. Because the moisture requirement of the granule in Chinese pharmacopoeia is less than 8.0%, and the moisture content of the Baoyuan decoction belt dry powder is about 3%, the humidity environment of the belt dry powder in the workshop production process is not more than 50%, and the exposure time is not more than 8 hours.

4 study of pelletization Process

4.1 examination of granulating Effect of different moisture bands dry powder

Taking 3 parts of Baoyuan decoction with dry powder (moisture 2.4%), and placing under 50% -60% of ambient humidity to absorb moisture until the moisture content is 3.5%, 4.5% and 5.5% respectively. The effect of different moisture content with dry powder on granulation was examined. The test results are shown in Table 11.

Table 11 table for investigating granulating effect of different moisture content of Baoyuan decoction with dry powder

The results show that: (1) the granulation molding rate of the Baoyuan decoction is increased along with the increase of the moisture content, the moisture content is 2.36 percent and 3.59 percent, the particle size is uniform, the color is uniform, and the appearance is stable; when the water content is 4.36%, slight grain phenomenon in an acceptable range appears; serious grain phenomenon appears when the water content is 5.40%. In combination with the early-stage moisture absorption experiment with dry powder, the moisture absorption of the dry powder reaches 3.61% in 8 hours, and the moisture content of the whole granule is controlled to be less than 8%, so that preliminary determination is made that the moisture content of the dry powder is controlled to be less than 4.5%, and the external exposure time of the Baoyuan decoction from the dry powder to the granulating process and the granule packaging process is not longer than 8 hours.

5 pilot test process validation

According to the technological parameters determined by the small-scale and pilot-scale technological researches of Baoyuan decoction, 3 continuous pilot-scale technological verification tests are carried out, dry extract rate, total content of ginsenoside Rg1+Re and characteristic spectrum are taken as investigation indexes, and the summary of detection results is shown in Table 12. The process losses are shown in figure 2.

Table 12 statistical table of test results of pilot-scale process verification of Baoyuan decoction

Table 12 the results show that: from extraction to drying, the loss of the dry paste is about 26%, the index component loss is about 26% (consistent with the loss of the dry paste, which indicates that the index component is not destroyed in the process), the whole process is stable, but the dry paste loss is more due to the poor equipment matching property and more pipeline residues.

5 comparative study of Normal pressure concentration and reduced pressure concentration

And (3) taking the Baoyuan decoction extract, concentrating part of the Baoyuan decoction extract in a single-effect concentrator under reduced pressure until the relative density is about 1.27 (the concentration time is about 3 hours), and concentrating the other part of the Baoyuan decoction extract in an open pot under normal pressure until the relative density is 1.27 (the concentration time is about 1.0 hour). The total content of ginsenoside Rg1+Re is taken as an investigation index. The results are shown in Table 13.

Table 13 comparative investigation table of reduced pressure concentration and normal pressure concentration

The results show that: in the normal pressure open concentration process, the total content of ginsenoside Rg1+Re is lost by about 30%, which indicates that the process causes damage to index components and the open concentration should be avoided as much as possible.

6-minute concentration and mixed concentration comparative test

And adopting a 500L extraction and concentration integrated machine to respectively carry out 1 batch of batch concentration and 1 batch of mixed concentration pilot scale process research. Concentrating in steps: concentrating the first extractive solution until it can not be concentrated again, and discharging; concentrating the second extractive solution until it can not be concentrated again, adding the first extractive solution and dextrin, concentrating until it can not be concentrated again, and discharging. Weighing, sampling, detecting and analyzing. Mixing and concentrating: extracting the first and second extractive solutions respectively, mixing, concentrating under reduced pressure to a density of about 1.15, adding melted dextrin, concentrating under reduced pressure to a specified density, and sampling and detecting. Results of the study table 14.

TABLE 14 comparative investigation table of fractional concentration and mixed concentration

Table 14 the results show that: under the same equipment condition, the heating time of the effective components can be shortened and the component destruction rate can be reduced by the multi-pass concentration compared with the mixed concentration.

The preparation method of the health-care solid preparation provided by the invention comprises the steps of decoction piece processing, soaking, extraction, centrifugation, plate and frame filtration, reduced pressure concentration, vacuum belt drying, dry granulation, packaging and the like. The preparation method provided by the invention has stable and controllable process, and can produce particles basically consistent with the quality standard of the Baoyuan Shang Jizhun sample. The auxiliary materials of the element-preserving solid preparation provided by the invention only contain dextrin, so that the element-preserving solid preparation is simple and healthy; the obtained granule has good solubility and high bioavailability, and has convenient administration and carrying, and better stability than traditional decoction.

The invention provides a basic source, a processing technology and quality standards of decoction pieces used for preparing the Baoyuan solid preparation, and provides upper and lower limits of content, so that the raw materials are ensured to be uniform and stable, and the quality of the preparation is controlled from the source.

The invention provides a soaking and extracting process of a primordial-qi-preserving solid preparation. Compared with the traditional Chinese patent medicine excessive extraction (generally, the extraction time is more than 1 hour in each pass, most of the actual extraction is invalid impurities, and active ingredients are easy to damage after long-term heating), the extraction method provided by the invention aims at the maximum extraction rate on the premise of ensuring that the extraction effect of the preparation and a reference sample is basically consistent, so that the later-stage technological process loss is compensated, and the technological parameters such as water addition amount, extraction times, extraction time and the like are determined. Compared with the reference sample preparation process, the water adding amount is reduced from 36 times to 10 times, the method is more suitable for modern industrialization requirements, the whole extraction time is less than 1.5h, and the method is more energy-saving and synergistic.

The invention provides a purification process of extracted liquid medicine. The invention adopts physical impurity removing modes such as centrifugation, plate-frame filtration and the like, the relative density, pH and index components of the liquid medicine do not change obviously before and after purification, the obtained particles have good dissolubility, and the solution does not float up or precipitate.

The invention provides a concentration method of a health-care solid preparation. The concentration method provided by the invention is reduced pressure concentration, the temperature is controlled at 80-90 ℃, and compared with the traditional normal pressure concentration mode, the method not only can improve the evaporation efficiency, but also can reduce the component damage. The traditional extraction liquid combining and concentrating mode is innovated into ' step-by-step concentration ' -mixing concentration ' (concentration after adding auxiliary materials), so that the heating time of index components of the element-preserving solid preparation is effectively reduced, the index component destruction rate is reduced from about 6% to 0%, and the problem of serious destruction of ginsenoside in the index components of the element-preserving solid preparation is solved. The research of the invention finds that the extraction rate of index components of the Baoyuan decoction pieces is about 80% in the first extraction process, and a conventional merging and concentrating mode is adopted in the modern Chinese patent medicine production, namely, the first extraction liquid is concentrated firstly, then the second extraction liquid is mixed into the first extraction liquid, and the first extraction liquid is continuously decompressed and concentrated to a specified relative density, and the index components in the first extraction liquid are always in a heated state in the concentrating mode, so that index components of the Baoyuan Shang Ren ginsenoside are seriously damaged. The method can effectively shorten the heating time of the ginsenoside and reduce the component damage by a multi-step concentration mode.

The invention provides a method for drying a solid preparation for protecting primordial qi. The drying method provided by the invention adopts vacuum belt type drying, the relative density of the liquid medicine is between 1.26 and 1.35, and the drying mode has low temperature, low energy consumption and less damage, and is especially suitable for materials with more heat sensitive components and high viscosity in the Baoyuan decoction preparation.

The invention provides the types and the amounts of auxiliary materials added and the adding nodes of the element-preserving solid preparation. The invention is different from the traditional adding before granulating, and the adding node of the auxiliary material is moved forward to the concentrating process, so that the problem of serious dry paste loss caused by large bubble (containing more saponins) and sticky tape in the process of drying the element-preserving solid preparation is solved, the auxiliary material and the liquid medicine can be uniformly mixed by adding in the concentrating process, and the relative loss caused by the residual liquid medicine pipeline is reduced. The storage environment and storage time of the materials are determined through investigation of hygroscopicity of the dry powder and the particles, and the stability of the preparation is ensured.

The invention provides an evaluation method of research process of a preparation method of a health-care solid preparation. According to the invention, the dry paste rate and ginsenoside Rg1+Re in the preparation process of the Baoyuan solid preparation are taken as main evaluation indexes, the dry paste loss and index component damage conditions of each stage in the preparation process of the Baoyuan solid preparation are researched, the aims of reducing the residual loss of a pipeline and index component damage are achieved, and the standard of the Baoyuan solid preparation is ensured to be in the standard range of a standard sample.

The invention provides a quality standard of a health-care solid preparation, which mainly comprises detection methods of prescription, preparation method, character, identification, inspection, content measurement (ginsenoside Rg1+Re, astragaloside IV), characteristic spectrum and the like, and establishes upper and lower limits of the content measurement according to mass transfer rules in the production process.

In the content measurement provided by the invention, two index components of ginsenoside Rg1+Re and astragaloside IV and characteristic patterns are the same sample solution and the same mobile phase, and the ginsenoside Rg1+Re and the characteristic patterns are completely consistent in detection method. The innovative detection method greatly improves the detection efficiency and reduces the energy consumption and the detection cost.

The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.

Claims

1. The preparation method of the element-preserving solid particles is characterized by comprising the following steps of:

soaking the primordial qi-preserving decoction pieces in water to obtain primordial qi-preserving presoaked liquid; the primordial energy-preserving decoction pieces comprise ginseng decoction pieces, astragalus root decoction pieces, cinnamon decoction pieces, liquorice decoction pieces and ginger decoction pieces, and the mass ratio of the ginseng decoction pieces to the astragalus root decoction pieces to the liquorice decoction pieces to the cinnamon decoction pieces to the ginger decoction pieces is 373:746:186:75: (100-300); during the soaking, the mass ratio of the water to the element-preserving decoction pieces is (8-14): 1; the soaking time is 30-60 min;

Performing first boiling extraction on the primordial preserving presoaked liquid to obtain first primordial water extract and primordial preserving dregs; the first boiling extraction comprises a heating stage heated by steam and a boiling heat preservation stage heated by steam; the heat preservation time of the boiling heat preservation stage is 40-50 min; the steam pressure in the heating stage is less than or equal to 0.2MPa; the steam pressure is 0.02-0.08 MPa;

mixing the primordial qi-preserving medicine residues with water for second boiling extraction, wherein the mass ratio of the water to the primordial qi-preserving decoction pieces is (6-12) 1, and the steam pressure in the heating stage is less than or equal to 0.2MPa; the steam pressure is 0.02-0.08 MPa, and a second water extract with element retention is obtained; the second boiling extraction comprises a heating stage heated by steam and a boiling heat preservation stage heated by steam; the heat preservation time of the boiling heat preservation stage is 30-35 min;

respectively carrying out first concentration and second concentration on the first and second water extract to obtain first and second concentrated solutions; the temperature of the first concentration and the second concentration is independently 70-90 ℃; the vacuum pressure of the first concentration and the second concentration is independently 0.02-0.05 MPa; the first concentration and the second concentration are independently carried out under the condition of steam heating, and the pressure of steam of the first concentration and the second concentration is independently less than or equal to 0.06MPa;

The first and second primordial energy-preserving concentrated solutions are combined to obtain the primordial energy-preserving soup;

mixing the Baoyuan decoction with the aqueous solution of dextrin, and concentrating to obtain the Baoyuan extract; the temperature of concentration is less than or equal to 90 ℃; the mass ratio of the dextrin to the Baoyuan decoction dry paste is (0.3-0.5): 1; the concentration temperature is 70-90 ℃; the vacuum pressure of the concentration is 0.02-0.05 MPa; the concentration is carried out under the condition of steam heating, and the pressure of the concentrated steam is less than or equal to 0.06MPa;

vacuum drying the Baoyuan extract to obtain the Baoyuan dry powder; the vacuum drying is vacuum belt drying; the working parameters of the vacuum belt drying include: the feeding temperature is 75-85 ℃; the feeding speed is 8-20L/h; the running speed of the crawler belt is 15+/-5 cm/min, the rotating speed of the distributing motor is 35-45 r/min, and the angle of the swing arm is 70-85 degrees; the heating temperature zone is as follows: one region 95.+ -. 5 ℃, two regions 96.+ -. 5 ℃ and three regions 96.+ -. 5 ℃; the vacuum degree is-0.10 to-0.09 MPa; the cooling temperature is 20-30 ℃;

granulating the Baoyuan dry powder in a dry method to obtain the Baoyuan granule; the dry granulation is carried out in a granulator, and the working parameters of the dry granulation comprise: the pressure of a compression roller of the granulator is 14-18 MPa; the rotating speed of a compression roller of the granulator is 4-8 r/min; the vertical rotating speed of a screw feeder of the granulator is 22-28 r/min; the horizontal rotating speed of a screw feeder of the granulator is 110-130 r/min; the grain finishing speed is 110-140 r/min.

2. The primordial-energy-preserving solid preparation prepared by the preparation method of claim 1 is characterized in that the dry paste rate of the primordial-energy-preserving solid preparation is 24-32%; the extract of the element-preserving solid preparation is 30-60%; the ginseng content of the prebiotic solid preparation is 4-9 mg/bag based on the total amount of ginsenoside Rg1 and ginsenoside Re; the content of astragalus root in the element-preserving solid preparation is 0.3-1.5 mg/bag calculated by astragaloside IV; the quality of 1 bag of the element-preserving solid preparation is 3.0g.