CN116509984A

CN116509984A - Preparation method of Sizhi decoction and Sizhi decoction

Info

Publication number: CN116509984A
Application number: CN202310627616.0A
Authority: CN
Inventors: 朱博云; 李丹丽; 王秋平
Original assignee: Beijing China Resources Hi Tech Natural Pharmaceutical Co ltd
Current assignee: Beijing China Resources Hi Tech Natural Pharmaceutical Co ltd
Priority date: 2023-05-30
Filing date: 2023-05-30
Publication date: 2023-08-01

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, and discloses a preparation method of a Sizhi decoction preparation and the Sizhi decoction preparation. In the preparation method provided by the invention, the liquid medicine can be promoted to achieve dynamic balance in thermodynamic and kinetic aspects and the like by carrying out primary heating concentration treatment on the water extraction mixed liquid, carrying out secondary heating concentration treatment on the alcohol precipitation filtrate and adding the mixing and co-heating step after adding the flavoring agent solution, so that the stability and clarity of the four-back soup are obviously improved.

Description

Preparation method of Sizhi decoction and Sizhi decoction

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a preparation method of a Sizhi decoction preparation and the Sizhi decoction preparation.

Background

The four-reverse decoction is mainly used for treating yang deficiency with the symptoms of spontaneous perspiration, cold sweat spontaneous discharge, cold limbs with the symptoms of adverse flow of qi, clear valley with the symptoms of weak pulse with the symptoms of cold dispelling effect of Yang Wenli, is known as a first party for restoring yang with the symptoms of adverse flow of qi, is commonly used for treating diseases such as coronary heart disease angina, heart failure, myocardial infarction and the like in modern clinic, and has good treatment effect.

The decoction is prepared from three medicines of thin aconite, dried ginger and honey-fried licorice root, and the preparation process involves a process route of dry Jiang Zhengliu, boiling and extracting the three medicines and precipitating with ethanol. However, in the process of realizing the invention, the inventor finds that the four-reverse soup finished product prepared in the related technology is easy to have problems of excessive precipitation and poor clarity of liquid medicine after being subjected to conditions of oxygen contact, heating, long-term standing and the like.

Disclosure of Invention

In view of the above, the invention provides a preparation method of a Sizhi decoction and a Sizhi decoction, which are used for solving the problems that the Sizhi decoction finished product prepared in the related technology is easy to cause excessive precipitation and poor in clarity after being subjected to conditions of oxygen contact, heating, long-term storage and the like.

In a first aspect, the invention provides a preparation method of a Sili decoction preparation, which comprises the following steps:

collecting water extract mixed solution of radix Aconiti lateralis Preparata, zingiberis rhizoma and radix Glycyrrhizae Preparata, and concentrating to obtain first solution;

taking the first solution, carrying out alcohol precipitation and standing, and carrying out solid-liquid separation once to obtain a second solution;

taking the second solution, carrying out secondary heating concentration and water sedimentation standing, and carrying out secondary solid-liquid separation to obtain a third solution;

taking the third solution, adding a flavoring agent solution, mixing and heating, and carrying out solid-liquid separation for three times to obtain a fourth solution;

and adding the preservative solution and the dried ginger volatile oil extract into the fourth solution to fix the volume.

The inventor researches that the traditional Chinese medicinal materials contain high molecular substances such as starch, gum, pectin, mucilage, protein, tannin, resin, pigment and the like, so that the prepared Sizhi Shang Chengpin medicinal liquid often contains some unstable components, but the conventional water extraction and alcohol precipitation method only can remove most of high molecular impurities in the medicinal liquid, and other substances such as alkaloid, salt, glycoside, organic acid and salt thereof, amino acid, saponin, anthraquinone, flavonoid, inorganic salt, tannin, pigment, resin, gum, pectin, protein, polysaccharide and the like can influence the stability and clarity of the Sizhi soup finished product, and particularly when Sizhi Shang Chengpin is contacted with oxygen, heated or placed for a long time, the problems of excessive precipitation and poor medicinal liquid clarity are more likely to occur.

In the preparation method provided by the invention, the liquid medicine can be promoted to achieve dynamic balance in thermodynamic and kinetic aspects and the like by carrying out primary heating concentration treatment on the water extraction mixed liquid, carrying out secondary heating concentration treatment on the alcohol precipitation filtrate and adding the mixing and co-heating step after adding the flavoring agent solution, so that the stability and clarity of the four-reverse soup are obviously improved.

In an alternative embodiment, the conditions of the primary heated concentration include: vacuum degree is-0.08 MPa-0 MPa, temperature is 60-100 ℃, and concentration is carried out until the target volume of the finished product is 30-50%;

optionally, the time of one-time heated concentration is 3-12 hours.

In an alternative embodiment, prior to subjecting the first solution to alcohol precipitation, further comprising the step of cooling the first solution to below 40 ℃;

optionally, the conditions for alcohol precipitation and standing include: the consumption of the alcohol solvent is 3-4 times of the volume of the first solution, and the standing time is 24-96 hours;

optionally, the temperature difference of the alcoholic solvent and the first solution is not more than 30 ℃;

optionally, the concentration of alcohol in the alcohol solvent is 80% -97%;

optionally, the primary solid-liquid separation comprises a clarifying plate filtration and a filter membrane filtration, wherein the pore diameter of the clarifying plate is 0.2-6 mu m, and the pore diameter of the filter membrane is 0.1-0.45 mu m.

In an alternative embodiment, the conditions of the secondary heated concentration include: vacuum degree is-0.08 MPa-0 MPa, temperature is 60-100 ℃, and concentration is carried out until the target volume of the finished product is 10-30%;

optionally, the secondary heating concentration time is 1-8 h.

In an alternative embodiment, prior to the water-sinking stand, further comprising the step of cooling the secondarily heated concentrate of the second solution to below 40 ℃;

optionally, the conditions of water sedimentation and standing include: the water consumption is 2-5 times of the volume of the secondary heated concentrated solution of the second solution, and the standing time is 24-96 hours;

optionally, the temperature difference between the water and the secondarily heated concentrate of the second solution is no more than 30 ℃;

optionally, the secondary solid-liquid separation comprises a clarifying plate filtration and a filter membrane filtration, wherein the pore diameter of the clarifying plate is 0.2-6 mu m, and the pore diameter of the filter membrane is 0.1-0.45 mu m.

In an alternative embodiment, the concentration of the flavoring solution is 0.70 g/mL-0.90 g/mL, and the amount of the flavoring solution is 0.5-0.6 times the volume of the third solution;

optionally, the flavoring agent comprises at least one of sucrose, sorbitol, and aspartame;

optionally, the temperature of the mixed co-heating is 60-100 ℃ and the time is 20-60 min;

optionally, the three solid-liquid separations include a clarifier filtration with a pore size of 0.2 μm to 6 μm and a filter membrane filtration with a pore size of 0.1 μm to 0.45 μm.

In an alternative embodiment, the concentration of the preservative solution is 0.012g/mL to 0.12g/mL, and the preservative solution is used in an amount of 0.022 to 0.028 times the volume of the fourth solution;

optionally, the preservative comprises at least one of sodium benzoate, potassium sorbate, methylparaben, and ethylparaben.

In an alternative embodiment, the four-way soup comprises the following raw materials in parts by weight:

300 parts of light aconite, 200 parts of dried ginger and 300 parts of honey-fried licorice root.

In the preparation method provided by the invention, the temperature difference between the liquid medicine and the alcohol solvent as well as the temperature difference between the liquid medicine and the water solvent are controlled to be not more than 30 ℃, the standard of standing time timing is standardized, and the modes of repeated filtration and the like are adopted by adopting a clarifying plate (fine filter paper board) and a filter membrane, so that the precipitation of active ingredients can be prevented, and meanwhile, the sufficient sedimentation and removal of impurity ingredients can be further ensured.

The preparation method provided by the invention has the advantages of wide raw material sources, low cost, no need of special equipment and the like, is suitable for large-scale preparation, and is beneficial to industrial production; the content (not lower than 0.55 mg/mL), pH, identification and other indexes of the prepared Sili decoction meet pharmacopoeia standards, and no precipitation occurs when the decoction is stored for at least 6 months under the conditions of 40+/-2 ℃ and 75+/-5%; the product has the functions of treating yang deficiency with symptoms of spontaneous perspiration, cold sweat, syncope and adverse reaction of limbs, clear grains, and slight pulse with obvious curative effect, and has the advantages of good economic benefit, wide application range, etc.

In a second aspect, the invention also provides a four-reverse soup preparation prepared by the method.

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 diagram showing the final product of the four-way soup prepared in example 1 of experimental example 1 of the present invention after 6 months stability examination under high temperature and high humidity conditions.

Detailed Description

The following examples are provided for a better understanding of the present invention and are not limited to the preferred embodiments described herein, but are not intended to limit the scope of the invention, any product which is the same or similar to the present invention, whether in light of the present teachings or in combination with other prior art features, falls within the scope of the present invention.

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.

In order to solve the above-mentioned problems in the related art, according to a first aspect of the present invention, there is provided a preparation method of a Sili soup preparation, comprising the steps of:

Wherein, the preparation process of the water extraction mixed solution and the dried ginger volatile oil extract can comprise (the double amount refers to the milliliter number of adding water to each gram of Chinese medicinal materials):

decocting radix Aconiti lateralis Preparata and radix Glycyrrhizae Preparata with water twice for 2 hr (7-10 times of water) and 1.5 hr (4-8 times of water), mixing decoctions, and filtering; extracting volatile oil from rhizoma Zingiberis by steam distillation, and keeping the volatile oil and distilled water solution for later use; decocting rhizoma Zingiberis recens residue in water for 1 hr (4-8 times of the amount), mixing the decoction with the above distilled water solution, filtering, and mixing with the decoction of radix Aconiti lateralis Preparata and radix Glycyrrhizae Preparata to obtain water extract mixture.

In an alternative embodiment, the conditions of the primary heated concentration include: vacuum degree is-0.08 MPa-0 MPa, temperature is 60-100 ℃, and concentration is carried out until the target volume of the finished product is 30-50%, for example 40%;

optionally, the time of the primary heated concentration is 3-12 hours, for example 10 hours.

optionally, the conditions for alcohol precipitation and standing include: the consumption of the alcohol solvent is 3-4 times of the volume of the first solution, and the standing time is 24-96 hours; for example, the amount of the alcohol solvent is 3 times the volume of the first solution, the standing time is 24 hours, and the standing can be refrigeration standing;

optionally, the concentration of alcohol in the alcohol solvent is 80% -97%;

In an alternative embodiment, the conditions of the secondary heated concentration include: vacuum degree is-0.08 MPa-0 MPa, temperature is 60-100 ℃, and concentration is carried out until the target volume of the finished product is 10-30%, for example 15%;

optionally, the time of the secondary heated concentration is 1h to 8h, for example 6h.

optionally, the conditions of water sedimentation and standing include: the water consumption is 2-5 times of the volume of the secondary heated concentrated solution of the second solution, and the standing time is 24-96 hours; illustratively, the standing is refrigerated standing for 24 hours;

The invention is described in further detail below in connection with specific examples which are not to be construed as limiting the scope of the invention as claimed.

Example 1

In the embodiment, 300g of light aconite, 200g of dried ginger, 300g of honey-fried licorice root, 255g of sucrose and 3g of sodium benzoate are used for preparing 1000mL of Sili soup, and the specific preparation method is as follows:

(1) Decocting radix Aconiti lateralis Preparata and radix Glycyrrhizae Preparata

Weighing 300g of light aconite and 300g of honey-fried licorice root according to the weight of the four-reverse decoction; mixing the light aconite and honey-fried licorice root, adding 4800mL of water (8 times of the amount), decocting for 2 hours, and filtering the decoction through a 80-mesh stainless steel sieve; adding 3600mL of water (6 times of the amount) into the filter residue, decocting for 1.5 hours, and filtering the decoction through a 80-mesh stainless steel sieve; mixing the two filtrates, and filtering with stainless steel sieve to obtain decoction of radix Aconiti lateralis Preparata and radix Glycyrrhizae Preparata.

(2) Distillation, boiling and extraction of dried ginger

200g of dried ginger is weighed and suspended on a 80-mesh stainless steel steaming drawer, steam distillation is carried out in a sealed stainless steel barrel filled with 2000mL of water, 50mL of volatile oil is extracted, and the volatile oil and distilled water solution are reserved; jiang Zhazhong decocting with 1200mL water (6 times of the above amount) for 1 hr, mixing the decoction with the distilled water solution, and filtering with 80 mesh stainless steel sieve to obtain rhizoma Zingiberis water extract.

(3) Concentrating the water extraction mixed solution by one-time heating

Mixing the decoction extract of the radix aconiti lateralis preparata, the honey-fried licorice root and the water extract of the dried ginger to obtain a water extract mixed solution, carrying out primary heating concentration for 10 hours (the vacuum degree is-0.08 MPa-0 MPa, the temperature is 60-100 ℃), and concentrating to 40% (about 400mL in volume) of the target volume of the finished product to obtain a first solution.

(4) Standing for alcohol precipitation

Cooling the first solution to below 40deg.C, adding 1200mL of 95% ethanol (the temperature difference between the first solution and 95% ethanol is not more than 30deg.C), stirring for 15min, refrigerating, and standing for 24 hr; after the standing, the obtained liquid medicine was filtered through a clarification plate (1.5-3 μm) +a polypropylene filter membrane (0.45 μm) to obtain a second solution.

(5) Water sinking and standing

Concentrating the second solution for 6h (vacuum degree: minus 0.08 MPa-0 MPa, temperature 60-100 ℃), concentrating to 20% (volume about 200 mL) of the target volume of the finished product, cooling to below 40 ℃, adding purified water to 600mL (the adding amount of the purified water is 2 times of the volume of the concentrated solution for secondary heating, and the temperature difference is not more than 30 ℃), refrigerating for 24h, and filtering the obtained liquid medicine through a clarifying plate (1.5-3 μm) +a polypropylene filter membrane (0.45 μm) to obtain a third solution.

(6) Preparation of simple syrup (taste corrigent solution)

Taking 135mL of purified water, heating to 60+/-5 ℃, adding 255g of sucrose, adding 300mL of purified water, stirring while adding, continuing to heat to 100 ℃, starting timing, heating for 5min to obtain monose syrup, filtering the monose syrup while the monose syrup is hot through a 200-mesh stainless steel screen, and cooling to 50-60 ℃.

(7) Preparing

Heating the third solution to 50-60deg.C, adding 300mL of monosaccharide slurry while stirring, continuously heating to 100deg.C, starting timing, mixing and heating for 20min, cooling, and filtering with a clarifying plate (1.5-3 μm) +polypropylene filter membrane (0.45 μm) to obtain fourth solution;

taking the fourth solution, adding 25mL of sodium benzoate solution (containing 3g of sodium benzoate), adding 50mL of the dried ginger volatile oil extract, adding water to a constant volume of 1000mL, stirring uniformly, filtering by a 0.45 mu m polypropylene filter membrane, and encapsulating.

(8) Filling, sealing and sterilizing

The above-mentioned medicinal liquid was filled into 10mL soda lime glass tube type oral liquid bottle (easy-to-pierce aluminum cap and silica gel plug for oral liquid bottle), and sterilized (sterilization condition: 100 ℃ C., 30 min).

Example 2

A Sili decoction was prepared as in example 1, except that in step (1), the light aconite and honey-fried licorice root were mixed, 4200mL of water (7 times) was added and decocted for 2 hours, and the decoction was filtered through a 80 mesh stainless steel screen; 3000mL of water (5 times) is added into the filter residue for decoction for 1.5 hours.

Example 3

A Sili decoction was prepared as in example 1, except that in step (1), the light aconite and honey-fried licorice root were mixed, 6000mL of water (10 times) was added and decocted for 2 hours, and the decoction was filtered through a 80 mesh stainless steel screen; 4800mL of water (8 times) was added to the residue to decoct for 1.5 hours.

Example 4

A Sili decoction was prepared as in example 1, except that in step (2), jiang Zhazhong was decocted with 1600mL of water (8 times the amount) for 1 hour, the decoction was combined with the distilled aqueous solution and filtered through a 80 mesh stainless steel screen to obtain a dried ginger aqueous extract.

Example 5

A four-way soup was prepared as in example 1, except that in step (3) of this example, the aqueous extract mixture was subjected to heat concentration once for 12 hours.

Example 6

A four-way soup was prepared as in example 1, except that in step (5) of this example, the second solution was subjected to secondary heat concentration for 8 hours.

Example 7

A four-way soup was prepared as in example 1, except that in step (7) of this example, after adding the single syrup to the third solution, the mixing and co-heating time was 60 minutes.

Comparative example 1

A four-reverse soup was prepared in the same manner as in example 1 except that the aqueous extract mixture was concentrated under reduced pressure at normal temperature in step (3) of this comparative example to obtain a first solution; and (5) decompressing the second solution at normal temperature and then standing by water precipitation.

Comparative example 2

A four-way soup was prepared as in example 1, except that the aqueous extract mixture was concentrated under reduced pressure at room temperature in step (3) of this comparative example to obtain a first solution.

Comparative example 3

A four-way soup was prepared as in example 1, except that the second solution was concentrated under reduced pressure at normal temperature in step (5) of this comparative example and then was subjected to water precipitation for standing.

Comparative example 4

A four-way decoction was prepared as in example 1, except that in step (7) of this comparative example, simple syrup, sodium benzoate solution, and the volatile oil extract of dried ginger were added sequentially and the volume was fixed, i.e., mixing and co-heating were not performed after the simple syrup was added in step (7).

Comparative example 5

A four-way decoction was prepared as in example 1, except that in step (7) of this comparative example, after adding single syrup to the third solution, mixing and co-heating, sodium benzoate solution and volatile oil extract of Zingiberis rhizoma were directly added and the volume was fixed without solid-liquid separation.

Experimental example 1

The four-way soup prepared in examples 1 to 7 and comparative examples 1 to 5 was stored under normal temperature conditions and high temperature and high humidity conditions (temperature 40.+ -. 2 ℃ C., humidity 75%.+ -. 5%) respectively, stability was examined for 6 months, and the time for precipitation of the medicinal liquid was observed and recorded during storage, and the results are shown in Table 1.

Table 1 time for precipitation of each of the four decoction solutions

Decoction for treating four adverse events	High temperature and high humidity precipitation time and day	Time of precipitation at normal temperature, day
			Example 1	No precipitate	No precipitate
Example 2	No precipitate	No precipitate
			Example 3	No precipitate	No precipitate
Example 4	No precipitate	No precipitate
			Example 5	No precipitate	No precipitate
Example 6	No precipitate	No precipitate
			Example 7	No precipitate	No precipitate
Comparative example 1	1	14
			Comparative example 2	10	125
Comparative example 3	10	130
			Comparative example 4	12	140
Comparative example 5	10	40

As can be seen from Table 1, the preparation method of the Sili decoction provided by the invention can promote the dynamic balance of the liquid medicine after the three medicines are fully combined in thermodynamic and kinetic aspects and the like by adopting a plurality of ways of heating and concentrating to treat the three medicine boiling extract and the alcohol precipitation filtrate related to the process route, adding the heating of the liquid medicine after single syrup and the like, and obviously improves the clarity and stability of the liquid medicine, thereby effectively relieving the problem of precipitation of the liquid medicine after long-term storage.

The final product diagram of the four-way soup prepared in example 1 after 6 months stability investigation under high temperature and high humidity conditions is shown in fig. 1.

Experimental example 2

The experimental example is used for verifying the influence of the preparation method of the invention on the content of the index component (glycyrrhizic acid) of the finished product of the Sili soup.

The four reverse soups prepared in examples 1 to 7 and comparative examples 1 to 5 were taken respectively, and the glycyrrhizic acid content in each liquid medicine was measured as follows:

(1) Chromatographic condition and System applicability test

Octadecylsilane chemically bonded silica is used as a filler; methanol-0.2 mol/L ammonium acetate solution-glacial acetic acid (67:33:1) is taken as a mobile phase; the detection wavelength was 250nm. The number of theoretical plates should be not less than 2000 calculated as glycyrrhizic acid peak.

(2) Preparation of control solution

Taking a proper amount of ammonium glycyrrhizate reference substance, precisely weighing, adding mobile phase to prepare a reference substance solution containing 0.4mg per 1mL (corresponding to 0.3918mg of glycyrrhizic acid per 1 mL).

(3) Preparation of test solutions

Precisely measuring 10mL of the sample, placing in a 50mL measuring flask, adding a mobile phase to a scale, shaking uniformly, and filtering to obtain a sample solution.

(4) Assay

Respectively precisely sucking 10 μl of the reference solution and the sample solution, and injecting into a liquid chromatograph for measurement. Each 1mL of the product contains glycyrrhizic acid (C) ₄₂ H ₆₂ O ₁₆ ) Not less than 0.50mg. The test results are shown in Table 2.

TABLE 2 glycyrrhizic acid content in each Sili decoction

As can be seen from Table 2, the preparation method of the Sili soup of the invention does not affect the content of the target ingredient of Sili Shang Zhongzhi.

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. The preparation method of the Sili decoction preparation is characterized by comprising the following steps:

2. The method of claim 1, wherein the one-time heated concentration conditions comprise: vacuum degree is-0.08 MPa-0 MPa, temperature is 60-100 ℃, and concentration is carried out until the target volume of the finished product is 30-50%;

optionally, the time of one-time heated concentration is 3-12 hours.

3. The method of preparing according to claim 1 or 2, further comprising the step of cooling the first solution to below 40 ℃ before subjecting the first solution to alcohol precipitation;

optionally, the concentration of alcohol in the alcohol solvent is 80% -97%;

4. A method of preparing according to any one of claims 1 to 3, wherein the conditions of the secondary heated concentration comprise: vacuum degree is-0.08 MPa-0 MPa, temperature is 60-100 ℃, and concentration is carried out until the target volume of the finished product is 10-30%;

optionally, the secondary heating concentration time is 1-8 h.

5. The method of any one of claims 1 to 4, further comprising the step of cooling the secondary heated concentrate of the second solution to below 40 ℃ prior to the water-sinking stand;

6. The method according to any one of claims 1 to 5, wherein the concentration of the taste-modifier solution is 0.70g/mL to 0.90g/mL, and the amount of the taste-modifier solution is 0.5 to 0.6 times the volume of the third solution;

7. The production method according to any one of claims 1 to 6, wherein the concentration of the preservative solution is 0.012g/mL to 0.12g/mL, and the amount of the preservative solution is 0.022 times to 0.028 times the volume of the fourth solution;

8. The preparation method according to any one of claims 1 to 7, wherein the four-reverse soup comprises the following raw materials in parts by weight:

9. A four-bar soup formulation prepared by the method of any one of claims 1 to 8.