阅读说明：本技术 含金银花的中药组合物、配方颗粒及其制备方法 (Traditional Chinese medicine composition containing honeysuckle, formula granules and preparation method thereof ) 是由 刘燎原 张雪兰 邓李红 张志鹏 陈江平 林伟雄 王寿富 魏梅 程学仁 孙冬梅 于 2020-03-23 设计创作，主要内容包括：本发明涉及含金银花的中药组合物、配方颗粒及其制备方法,该制备方法包括以下步骤：将金银花和连翘加水合煎,得到煎煮液和挥发油；将挥发油进行包合处理,干燥,得到挥发油包合物；将煎煮液进行浓缩,得到浓缩物,挥发油包合物和浓缩物即为所述中药组合物。上述制备方法可以解决目前制备单味金银花配方颗粒时挥发油含量低、难收集、得率低的问题,同时还可以解决连翘中药配方颗粒在清膏干燥时挥发油逸失,从而导致与物质基础与传统汤剂存在差异的问题。(The invention relates to a traditional Chinese medicine composition containing honeysuckle, a formula particle and a preparation method thereof, wherein the preparation method comprises the following steps: decocting flos Lonicerae and fructus forsythiae with water to obtain decoction and volatile oil; clathrating the volatile oil, and drying to obtain volatile oil clathrate; concentrating the decoction to obtain a concentrate, and obtaining the volatile oil inclusion compound and the concentrate, namely the traditional Chinese medicine composition. The preparation method can solve the problems of low volatile oil content, difficult collection and low yield in the existing preparation of single honeysuckle flower formula particles, and can also solve the problem that volatile oil is lost when the fructus forsythiae traditional Chinese medicine formula particles are dried in clear paste, so that the substance basis of the fructus forsythiae traditional Chinese medicine formula particles is different from that of traditional decoction.)

1. A preparation method of a traditional Chinese medicine composition containing honeysuckle is characterized by comprising the following steps:

decocting flos Lonicerae and fructus forsythiae with water to obtain decoction and volatile oil;

performing inclusion treatment on the volatile oil, and drying to obtain a volatile oil inclusion compound;

and concentrating the decoction to obtain a concentrate, wherein the volatile oil inclusion compound and the concentrate are the traditional Chinese medicine composition.

2. The preparation method according to claim 1, wherein the mass ratio of the honeysuckle to the forsythia suspense is 1: (0.25-2); and/or

The mass ratio of the honeysuckle to the water is 1: (3-9).

3. The preparation method according to claim 1, wherein the step of decocting the honeysuckle and the forsythia suspense in water comprises the steps of:

mixing the honeysuckle and the forsythia, adding water for steam distillation, and collecting volatile oil to obtain volatile oil and distilled decoction pieces;

decocting the distilled decoction pieces in water, and performing solid-liquid separation to obtain a first decoction liquid and a first decoction residue;

adding water into the first decoction dregs for decoction, and performing solid-liquid separation to obtain a second decoction liquid and second decoction dregs;

repeating the operation for n times to obtain the nth decoction and the nth decoction residue, and mixing the decoctions to obtain the decoction, wherein n is an integer greater than or equal to 1.

4. The method according to any one of claims 1 to 3, wherein in the step of subjecting the volatile oil to inclusion treatment, the inclusion treatment is performed using β -cyclodextrin; and/or

In the step of concentrating the decoction, the operation conditions are as follows: the temperature is 45-85 ℃, the pressure is 0.00-0.095 MPa, and the concentration is carried out until the relative density of the concentrate is 1.01-1.20.

5. A preparation method of a honeysuckle-containing traditional Chinese medicine formula particle is characterized by comprising the following steps:

providing the traditional Chinese medicine composition according to the preparation method of any one of claims 1 to 4;

mixing the volatile oil inclusion compound and the concentrate with pharmaceutically acceptable auxiliary materials, drying, and granulating to obtain the traditional Chinese medicine formula granule.

6. The method of claim 5, wherein the steps of mixing the clathrate of essential oils and the concentrate with pharmaceutically acceptable excipients, drying, and granulating comprise the steps of:

mixing the volatile oil inclusion compound, the concentrate and a first auxiliary material, and drying to obtain an intermediate;

crushing the intermediate, mixing the crushed intermediate with the second auxiliary material, and granulating;

wherein the first auxiliary material comprises one or more of a filler and a binder;

the second auxiliary material comprises one or more of a lubricant, a disintegrant and a binder.

7. The method according to claim 6, wherein the filler is one or more of dextrin, maltodextrin, starch and lactose; and/or

The lubricant is one or more of silicon dioxide and magnesium stearate; and/or

The disintegrating agent is starch; and/or

The adhesive is one or more of dextrin, maltodextrin, lactose and polyvidone.

8. The honeysuckle-containing traditional Chinese medicine composition prepared by the preparation method of any one of claims 1 to 4.

9. The honeysuckle-containing traditional Chinese medicine formula particle prepared by the preparation method of any one of claims 5 to 7.

10. The honeysuckle-containing traditional Chinese medicine composition is characterized by being prepared from honeysuckle and fructus forsythiae, wherein the mass ratio of the honeysuckle to the fructus forsythiae is 1: (0.25-2).

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparation, in particular to a traditional Chinese medicine composition containing honeysuckle, a formula particle and a preparation method thereof.

Background

Honeysuckle is the most commonly used medicine for treating exogenous wind-heat, early stage of epidemic febrile disease, pyocutaneous disease, bacteria resistance and inflammation diminishing, honeysuckle is light in mass and aromatic in smell, and has the effects of clearing heat in the qi system, relieving the toxin in the blood system and better dispelling wind and heat. Modern pharmacological research shows that honeysuckle has the wide effects of resisting inflammation, resisting bacteria, improving immunity, relieving fever, resisting free radical damage and the like, wherein the volatile oil is one of the main active ingredients of the medicine. But the honeysuckle volatile oil has low content, difficult collection and low yield.

The experiment report of the literature 'extraction of honeysuckle volatile oil and component analysis thereof by co-water distillation' (journal of university of agriculture in Henan, Vol. 51, No. 5 in 2017, page 711 and 716): the honeysuckle flower is ground to be 0.85mm, soaked in 5% sodium chloride solution for 28h, and extracted for 42h under the condition that the material-liquid ratio is 1:10(g: ml), and the yield of the volatile oil is only 0.171%. The extraction mode deviates from the preparation process of traditional Chinese medicine decoction in the management Specification of traditional Chinese medicine decoction Chamber of medical institution, the sodium chloride raw material in the non-prescription is added, and the extraction lasts for 42 hours, so that the water-soluble non-volatile chlorogenic acids in the honeysuckle are completely destroyed, and the extraction method is completely infeasible in the industrial production process.

In addition to the CO-water distillation, there are single methods for extracting volatile oil such as Soxhlet extraction, microwave extraction, and ultrasonic extraction, which have problems of incomplete extraction components and low extraction efficiency (Shandong chemical engineering, vol 47, 10 th of 2018, pp 51-53), and also have applications such as supercritical CO₂The extraction method and the subcritical R134a extraction (33, 13, 2012, 197-200) are used for extracting volatile oil from honeysuckle flower, although the yield is slightly improved, the obtained extract is fat-soluble substance, is not a pure volatile component, and has a larger difference from the traditional Chinese medicine formula particle substance basis which is extracted by water, except that the equipment operation cost is high. Based on the difficulty of collecting the volatile components of honeysuckle, the extraction of the volatile oil is abandoned in the standard preparation process of the traditional Chinese medicine formula granules of honeysuckle disclosed by the Commission of the national formulary. In fact, most of the volatile oil is dissolved and emulsified in the traditional decoction in the water extraction process, so that the preparation prepared by the preparation method of the published honeysuckle flower formula granules is different from the traditional decoction in quality, and the safety and the effectiveness of clinical use cannot be measured.

Disclosure of Invention

Based on the above, there is a need for a honeysuckle-containing traditional Chinese medicine composition, a formula granule and a preparation method thereof. The preparation method of the traditional Chinese medicine composition can solve the problems of low content, difficult collection and low yield of the honeysuckle volatile oil.

A preparation method of a traditional Chinese medicine composition containing honeysuckle comprises the following steps:

decocting flos Lonicerae and fructus forsythiae with water to obtain decoction and volatile oil;

performing inclusion treatment on the volatile oil, and drying to obtain a volatile oil inclusion compound;

and concentrating the decoction to obtain a concentrate, wherein the volatile oil inclusion compound and the concentrate are the traditional Chinese medicine composition.

In one embodiment, the mass ratio of the honeysuckle to the forsythia is 1: (0.25-2); and/or

The mass ratio of the honeysuckle to the water is 1: (3-9).

In one embodiment, the step of decocting the honeysuckle and the forsythia with water comprises the following steps:

mixing the honeysuckle and the forsythia, adding water for steam distillation, and collecting volatile oil to obtain volatile oil and distilled decoction pieces;

decocting the distilled decoction pieces in water, and performing solid-liquid separation to obtain a first decoction liquid and a first decoction residue;

adding water into the first decoction dregs for decoction, and performing solid-liquid separation to obtain a second decoction liquid and second decoction dregs;

repeating the operation for n times to obtain the nth decoction and the nth decoction residue, and mixing the decoctions to obtain the decoction, wherein n is an integer greater than or equal to 1.

In one embodiment, in the step of performing inclusion treatment on the volatile oil, the volatile oil is subjected to inclusion treatment by adopting beta-cyclodextrin; and/or

In the step of concentrating the decoction, the operation conditions are as follows: the temperature is 45-85 ℃, the pressure is 0.00-0.095 MPa, and the concentration is carried out until the relative density of the concentrate is 1.01-1.20.

A preparation method of a honeysuckle-containing traditional Chinese medicine formula particle comprises the following steps:

providing the traditional Chinese medicine composition according to the preparation method;

mixing the volatile oil inclusion compound and the concentrate with pharmaceutically acceptable auxiliary materials, drying, and granulating to obtain the traditional Chinese medicine formula granule.

In one embodiment, the steps of mixing the volatile oil inclusion compound and the concentrate with pharmaceutically acceptable excipients, drying and granulating comprise the following steps:

mixing the volatile oil inclusion compound, the concentrate and a first auxiliary material, and drying to obtain an intermediate;

crushing the intermediate, mixing the crushed intermediate with the second auxiliary material, and granulating;

wherein the first auxiliary material comprises one or more of a filler and a binder;

the second auxiliary material comprises one or more of a lubricant, a disintegrant and a binder.

In one embodiment, the filler is one or more of dextrin, maltodextrin, starch and lactose; and/or

The lubricant is one or more of silicon dioxide and magnesium stearate; and/or

The disintegrating agent is starch; and/or

The adhesive is one or more of dextrin, maltodextrin, lactose and polyvidone.

The honeysuckle-containing traditional Chinese medicine composition prepared by the preparation method.

The honeysuckle-containing traditional Chinese medicine formula particle prepared by the preparation method.

A traditional Chinese medicine composition containing honeysuckle flowers is prepared from honeysuckle flowers and fructus forsythiae, wherein the mass ratio of the honeysuckle flowers to the fructus forsythiae is 1: (0.25-2).

Through a large number of researches, the technical personnel of the invention find that the honeysuckle volatile oil has low content, difficult collection and low yield, but the forsythia volatile oil has high content, easy collection and high yield, and can utilize the principle of similar intermiscibility of organic components to combine the honeysuckle and the forsythia, and the honeysuckle volatile oil is enriched and distilled out along with the forsythia volatile oil with water vapor when the forsythia volatile oil is extracted through a medicine pair consisting of the honeysuckle and the forsythia, so that the problems of low content, difficult collection and low yield of the volatile oil when single-flavor honeysuckle formula particles are prepared at present can be solved, and the problem that the volatile oil is lost when the forsythia traditional Chinese medicine formula particles are dried in clear paste, so that the difference exists between the material basis and the traditional decoction is solved.

Detailed Description

In order that the invention may be more fully understood, a more particular description of the invention will now be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

The invention provides a honeysuckle-containing traditional Chinese medicine composition, which is prepared from honeysuckle and forsythia suspense, wherein the mass ratio of honeysuckle to forsythia suspense is 1: (0.25-2).

The honeysuckle and the forsythia are mixed together to form a honeysuckle-forsythia medicine pair, so that the medicine effect of the composition can be enhanced, and modern pharmacological studies also show that the honeysuckle and forsythia medicine pair has wide effects of resisting inflammation, resisting bacteria, improving immunity, relieving fever, resisting free radical damage and the like. Particularly, the technical personnel of the invention find that the quality ratio of the honeysuckle and the forsythia is controlled within the range, the synergistic effect between the honeysuckle and the forsythia can be further improved, and the preparation of the traditional Chinese medicine composition is also convenient.

The invention provides a preparation method of a traditional Chinese medicine composition containing honeysuckle, which comprises the following steps:

s101, adding water into honeysuckle and forsythia to decoct, and obtaining decoction and volatile oil.

It can be understood that the honeysuckle and the forsythia in the step S101 may be processed medicinal materials, such as honeysuckle decoction pieces and forsythia decoction pieces, or fresh medicinal materials; and step S101 may further include the steps of pre-treating the medicinal materials such as cleaning, shearing, and crushing.

Through a large number of researches, the technical personnel of the invention find that the honeysuckle volatile oil has low content, difficult collection and low yield, but the forsythia volatile oil has high content, easy collection and high yield, and can utilize the principle of similar intermiscibility of organic components to combine the honeysuckle and the forsythia, and the honeysuckle volatile oil is enriched and distilled out along with the forsythia volatile oil with water vapor when the forsythia volatile oil is extracted through a medicine pair consisting of the honeysuckle and the forsythia, so that the problems of low content, difficult collection and low yield of the volatile oil when single-flavor honeysuckle formula particles are prepared at present can be solved, and the problem that the volatile oil is lost when the forsythia traditional Chinese medicine formula particles are dried in clear paste, so that the difference exists between the material basis and the traditional decoction is solved.

Further, in step S101, the mass ratio of the honeysuckle to the forsythia is 1: (0.25-2); furthermore, the mass ratio of the honeysuckle to the forsythia is 1: 1. by controlling the mass ratio of the honeysuckle flower and the forsythia suspense within the range, on one hand, the honeysuckle flower-forsythia suspense medicine pair under the proportion has better medicine effect, and on the other hand, the proportion can enhance the interaction of the honeysuckle flower and the forsythia suspense in the volatile oil extraction process, and the extraction rate of the volatile oil is improved.

Further, the mass ratio of the honeysuckle to the water is 1: (3-9) to further improve the extraction rate of the volatile oil.

Further, step S101 includes the steps of:

s1011: mixing flos Lonicerae and fructus forsythiae, adding water, steam distilling, and collecting volatile oil to obtain volatile oil and distilled decoction pieces.

Preferably, the steam distillation time in the step S011 is 1-3 h; in addition, the medicinal materials can be soaked for a period of time (preferably 30min-40min) before steam distillation, so as to facilitate the subsequent steps.

S1012: decocting the distilled decoction pieces with water, and performing solid-liquid separation to obtain a first decoction liquid and a first decoction residue; decocting the first decoction dregs in water, and performing solid-liquid separation to obtain a second decoction liquid and second decoction dregs; repeating the operation for n times to obtain the nth decoction and the nth decoction residue, and mixing the decoctions to obtain the decoction, wherein n is an integer greater than or equal to 1.

The effective components can be fully dissolved in the decoction liquid through multiple times of decoction. Wherein, the time of each decoction can be adjusted according to the needs, preferably the time of each decoction is 10min-30min, and the time of each decoction can be the same or different, preferably the time of each decoction is gradually decreased. In one embodiment, the first decoction time is 15-25 minutes and the second decoction time is 10-20 minutes.

S102: clathrating the volatile oil, and drying to obtain volatile oil clathrate;

it is understood that the volatile oil may be pre-treated, such as by filtration, prior to inclusion to remove impurities that may be incorporated into the volatile oil. The inclusion treatment may be carried out by a conventional method, and is not particularly limited. In one embodiment, the inclusion treatment is performed with beta-cyclodextrin.

The drying method is not particularly limited, and the drying can be carried out by a conventional drying method, and preferably by spray drying.

S103, concentrating the decoction to obtain a concentrate, wherein the volatile oil inclusion compound and the concentrate are the required traditional Chinese medicine composition.

It is understood that, in step S103, the decoction may be concentrated according to the requirements of the specific preparation. Preferably, the concentration is carried out by reduced pressure and low temperature methods to avoid damage to the active ingredient. Further, the conditions for concentration are: the temperature is 45-85 ℃, and the pressure is 0.00-0.095 MPa.

It is understood that the above-mentioned Chinese medicinal composition can be made into various dosage forms according to the requirements, including but not limited to: pills, powders, granules, capsules, tablets and the like, which are not particularly limited herein, should be understood to be within the scope of the present invention.

Further, the traditional Chinese medicine composition is preferably prepared into traditional Chinese medicine formula granules. The method effectively solves the problems of low content, difficult collection and low yield of volatile oil when single honeysuckle flower formula particles are prepared at present, and simultaneously can solve the problem that volatile oil is lost when forsythia fruit traditional Chinese medicine formula particles are dried to cause difference between the material basis and the traditional decoction, so the method is suitable for preparing the traditional Chinese medicine formula particles, is convenient for the prescription adjustment of traditional Chinese medicine, greatly improves the compliance of production and clinical medication, and has excellent application prospect.

The invention also provides a traditional Chinese medicine composition containing honeysuckle flower, which is prepared by the preparation method.

The invention also provides a preparation method of the honeysuckle-containing traditional Chinese medicine formula granule, which comprises the following steps:

s201: preparing a traditional Chinese medicine composition;

the method for preparing the Chinese medicinal composition is as described in steps S101-S103, and is not repeated herein.

S202: mixing the volatile oil clathrate and the concentrate with pharmaceutically acceptable adjuvants, drying, granulating, and making into granule.

It is understood that the auxiliary material in step S202 may be any auxiliary material acceptable in the art, and is not particularly limited herein, and should be understood as falling within the scope of the present invention. In addition, the volatile oil inclusion compound, the concentrate and auxiliary materials can be respectively mixed according to requirements to respectively prepare corresponding products; the mixture of the volatile oil inclusion compound and the concentrate may also be mixed with an auxiliary material to prepare a mixed product, which is not particularly limited herein.

Further, step S202 includes the steps of:

s2021: mixing the volatile oil inclusion compound, the concentrate and a first auxiliary material, and drying to obtain an intermediate;

wherein, the first auxiliary material comprises one or more of a filling agent and a bonding agent;

further, the filler is one or more of dextrin, maltodextrin, starch and lactose.

Further, the lubricant is one or more of silicon dioxide and magnesium stearate.

S2022: crushing the intermediate, mixing the crushed intermediate with the second auxiliary materials, and granulating;

wherein the second auxiliary material comprises one or more of a lubricant, a disintegrating agent and a binder.

Further, the disintegrant is starch.

Further, the binder is one or more of dextrin, maltodextrin, lactose and povidone.

The invention also provides the honeysuckle-containing traditional Chinese medicine formula particle prepared by the preparation method.

The preparation method can effectively solve the problems of low volatile oil content, difficult collection and low yield when the single honeysuckle flower formula particle is prepared at present, and can also solve the problem of volatile oil loss when the forsythia suspense traditional Chinese medicine formula particle is dried in clear paste, so that the formula particle prepared by the method has no obvious difference from the traditional decoction, is beneficial to the dispensing of traditional Chinese medicine prescription drugs, and is particularly suitable for clinical medication. The honeysuckle and the forsythia are mixed together to form a honeysuckle-forsythia medicine pair, so that the medicine effect of the composition can be enhanced, modern pharmacological studies also show that the honeysuckle and forsythia medicine pair has wide effects of resisting inflammation, resisting bacteria, improving immunity, relieving fever, resisting free radical damage and the like, and the volatile oil is one of main active ingredients of the medicine pair.

Example 1

The preparation steps of the traditional Chinese medicine formula granule of the embodiment are as follows:

(1) the preparation raw materials comprise: honeysuckle decoction pieces, weeping forsythia decoction pieces, maltodextrin, beta-cyclodextrin, silicon dioxide and magnesium stearate.

(2) The preparation of the traditional Chinese medicine granule composition of the honeysuckle-forsythia medicine pair comprises the following steps: taking 75kg of honeysuckle decoction pieces and 75kg of forsythia decoction pieces, adding 450L of water, soaking for 30 minutes, carrying out steam distillation for 1-3 hours, and collecting volatile oil to obtain volatile oil and distilled decoction pieces; filtering the volatile oil, adding beta-cyclodextrin for clathration, and drying to obtain volatile oil clathrate; adding 1800L of water into the distilled decoction pieces, heating and decocting for 20 minutes, and carrying out solid-liquid separation to obtain a first decoction and dregs; adding 1500L of water into the residues, continuously heating and decocting for 15 minutes, filtering to obtain a second decoction, mixing the first decoction and the second decoction to obtain a decoction, concentrating the decoction under reduced pressure at 45-85 ℃ to obtain a concentrate with the relative density of 1.01-1.20, mixing the concentrate with maltodextrin, spray-drying to obtain a dry extract, mixing the dry extract with the volatile oil inclusion compound, silicon dioxide and magnesium stearate, and performing dry granulation to obtain the traditional Chinese medicine formula granules in the embodiment 1.

Example 2

The preparation steps of the traditional Chinese medicine formula granule of the embodiment are as follows:

(1) the preparation raw materials comprise: honeysuckle decoction pieces, weeping forsythia decoction pieces, maltodextrin, beta-cyclodextrin, silicon dioxide, magnesium stearate and starch.

(2) The preparation of the traditional Chinese medicine granule composition of the honeysuckle-forsythia medicine pair comprises the following steps: taking 100kg of honeysuckle decoction pieces and 50kg of fructus forsythiae decoction pieces, adding 450L of water, soaking for 30 minutes, carrying out steam distillation for 1-3 hours, and collecting volatile oil to obtain volatile oil and distilled decoction pieces; filtering the volatile oil, adding beta-cyclodextrin for clathration, and drying to obtain volatile oil clathrate; adding 1800L of water into the distilled decoction pieces, heating and decocting for 20 minutes, and carrying out solid-liquid separation to obtain a first decoction and dregs; adding 1500L of water into the residues, continuously heating and decocting for 15 minutes, filtering to obtain a second decoction, mixing the first decoction and the second decoction to obtain a decoction, concentrating the decoction under reduced pressure at 45-85 ℃ to obtain a concentrate with the relative density of 1.01-1.20, mixing the concentrate with maltodextrin, spray-drying to obtain a dry extract, mixing the dry extract with the volatile oil inclusion compound, silicon dioxide, magnesium stearate and starch, and performing dry granulation to obtain the traditional Chinese medicine formula granules in the embodiment 2.

Example 3

The preparation steps of the traditional Chinese medicine formula granule of the embodiment are as follows:

(1) the preparation raw materials comprise: honeysuckle decoction pieces, weeping forsythia decoction pieces, lactose, beta-cyclodextrin, silicon dioxide, magnesium stearate and dextrin.

(2) The preparation of the traditional Chinese medicine granule composition of the honeysuckle-forsythia medicine pair comprises the following steps: taking 50kg of honeysuckle decoction pieces and 100kg of fructus forsythiae decoction pieces, adding 450L of water, soaking for 30 minutes, carrying out steam distillation for 1-3 hours, and collecting volatile oil to obtain volatile oil and distilled decoction pieces; filtering the volatile oil, adding beta-cyclodextrin for clathration, and drying to obtain volatile oil clathrate; adding 1800L of water into the distilled decoction pieces, heating and decocting for 20 minutes, and carrying out solid-liquid separation to obtain a first decoction and dregs; adding 1500L of water into the residues, continuously heating and decocting for 15 minutes, filtering to obtain a second decoction, mixing the first decoction and the second decoction to obtain a decoction, concentrating the decoction under reduced pressure at 45-85 ℃ to obtain a concentrate with the relative density of 1.01-1.20, mixing the concentrate with lactose, spray-drying to obtain a dry extract, mixing the dry extract with the volatile oil inclusion compound, silicon dioxide, magnesium stearate and dextrin, and performing dry granulation to obtain the traditional Chinese medicine formula granules in the embodiment 3.

Example 4

The preparation steps of the traditional Chinese medicine formula granule of the embodiment are as follows:

(1) the preparation raw materials comprise: honeysuckle decoction pieces, weeping forsythia decoction pieces, dextrin, starch, beta-cyclodextrin, silicon dioxide, magnesium stearate and povidone.

(2) The preparation of the traditional Chinese medicine granule composition of the honeysuckle-forsythia medicine pair comprises the following steps: taking 75kg of honeysuckle decoction pieces and 75kg of forsythia decoction pieces, adding 300L of water, soaking for 30 minutes, carrying out steam distillation for 1-3 hours, and collecting volatile oil to obtain volatile oil and distilled decoction pieces; filtering the volatile oil, adding beta-cyclodextrin for clathration, and drying to obtain volatile oil clathrate; adding 1500L water into the distilled decoction pieces, heating and decocting for 30min, and performing solid-liquid separation to obtain a first decoction and medicinal residues; adding 1200L of water into the dregs of a decoction, continuously heating and decocting for 30 minutes, filtering to obtain a second decoction, mixing the first decoction and the second decoction to obtain a decoction, concentrating the decoction under reduced pressure at 45-85 ℃ to obtain a concentrate with the relative density of 1.01-1.20, mixing the concentrate with dextrin and starch, carrying out vacuum crawler-type drying to obtain a dry extract, mixing the dry extract with the volatile oil inclusion compound, silicon dioxide, magnesium stearate and povidone, and carrying out dry granulation to obtain the traditional Chinese medicine formula granule of the embodiment 4.

Comparative example 1

The preparation steps of the single honeysuckle flower formula particle of the comparative example are as follows:

(1) the preparation raw materials comprise: honeysuckle decoction pieces, maltodextrin, beta-cyclodextrin, silicon dioxide and magnesium stearate.

(2) Preparing a single honeysuckle formula particle: taking 150kg of honeysuckle decoction pieces, adding 450L of water, soaking for 30 minutes, carrying out steam distillation for 1-3 hours, and collecting volatile oil to obtain volatile oil and distilled decoction pieces; filtering the volatile oil, adding beta-cyclodextrin for clathration, and drying to obtain volatile oil clathrate; adding 1800L of water into the distilled decoction pieces, heating and decocting for 20 minutes, and carrying out solid-liquid separation to obtain a first decoction and dregs; adding 1500L of water into the dregs of a decoction, continuously heating and decocting for 15 minutes, filtering to obtain a second decoction, mixing the first decoction and the second decoction to obtain a decoction, concentrating the decoction under reduced pressure at 45-85 ℃ to obtain a concentrate with the relative density of 1.01-1.20, mixing the concentrate with maltodextrin, spray-drying to obtain a dry extract, mixing the dry extract with the volatile oil inclusion compound, silicon dioxide and magnesium stearate, and performing dry granulation to obtain the single-ingredient honeysuckle flower formula granules of the comparative example 1.

Comparative example 2

The preparation steps of the single-ingredient forsythia suspense formula particle of the comparative example are as follows:

(1) the preparation raw materials comprise: fructus forsythiae decoction pieces, maltodextrin, beta-cyclodextrin, silicon dioxide and magnesium stearate.

(2) Preparing a single-ingredient forsythia suspense formula particle: taking 150kg of fructus forsythiae decoction pieces, adding 450L of water, soaking for 30 minutes, performing steam distillation for 1-3 hours, and collecting volatile oil to obtain volatile oil and distilled decoction pieces; filtering the volatile oil, adding beta-cyclodextrin for clathration, and drying to obtain volatile oil clathrate; adding 1800L of water into the distilled decoction pieces, heating and decocting for 20 minutes, and carrying out solid-liquid separation to obtain a first decoction and dregs; adding 1500L of water into the residues, continuously heating and decocting for 15 minutes, filtering to obtain a second decoction, mixing the first decoction and the second decoction to obtain a decoction, concentrating the decoction under reduced pressure at 45-85 ℃ to obtain a concentrate with the relative density of 1.01-1.20, mixing the concentrate with maltodextrin, spray-drying to obtain a dry extract, mixing the dry extract with the volatile oil inclusion compound, silicon dioxide and magnesium stearate, and performing dry granulation to obtain the single-ingredient fructus forsythiae formula granules of the comparative example 2.

Comparative example 3

The composite formula particle of the comparative example is the case that the single honeysuckle formula particle of the comparative example 1 and the single forsythia formula particle of the comparative example 2 are used together according to the ratio of 1: 1.

Comparative example 4

The composite formula particle of the comparative example is the case that the single-component honeysuckle formula particle of the comparative example 1 and the single-component forsythia formula particle of the comparative example 2 are combined according to the ratio of 1: 0.5.

Comparative example 5

The composite formula particle of the comparative example is the case that the single-component honeysuckle formula particle of the comparative example 1 and the single-component forsythia formula particle of the comparative example 2 are used together according to the ratio of 0.5: 1.

Index measurement

The volatile oil yield, the chlorogenic acid content, the phillyrin content and the forsythiaside A content of the samples of examples 1 to 4 and comparative examples 1 to 5 are measured, the measurement results are shown in Table 1 in examples 1 to 4, Table 2 in comparative examples 1 to 5, and the increase rate results of the volatile oil yield and the index component content are shown in Table 3.

Wherein, the yield of the volatile oil is equal to the collection amount (mL) of the volatile oil/the amount (g) of decoction pieces

The yield increase rate of the volatile oil is equal to that of the volatile oil in the example/the theoretical yield of the volatile oil of the comparative example 1 and the comparative example 2 is multiplied by 100 percent according to the weight proportion of the decoction pieces in the corresponding example

The increase rate of the index component content is (index component content of experimental example-corresponding index component content of comparative example)/corresponding index component content of comparative example x 100%

Index component content measuring method

Chlorogenic acid: the measurement is carried out by high performance liquid chromatography (2015 version of general rules 0512 in China).

Octadecylsilane chemically bonded silica is used as a filler in chromatographic conditions and system applicability tests; acetonitrile-0.4% phosphoric acid solution (13: 87) is used as a mobile phase; the detection wavelength was 327 nm. The number of theoretical plates is not less than 1000 calculated according to chlorogenic acid peak.

Preparation of control solutions: precisely weighing appropriate amount of chlorogenic acid reference substance, placing in brown measuring flask, and adding 50% methanol to obtain solution containing 80 μ g per 1mL (stored at below 10 deg.C).

Preparation of a test solution: taking the product, grinding, precisely weighing about 0.1g, placing in a conical flask with a plug, precisely adding 50mL of 50% methanol solution, weighing, ultrasonically treating (power 200W, frequency 53kHz) for 30 minutes, cooling, supplementing the lost weight with 50% methanol solution, shaking uniformly, filtering, and taking the subsequent filtrate.

The determination method comprises the following steps: precisely sucking 10 μ L of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring.

Phillyrin: the determination is carried out by referring to high performance liquid chromatography (China pharmacopoeia 2015 edition general rules 0512).

Chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; acetonitrile-water (22:78) is used as a mobile phase; the flow rate was 0.4mL per minute; the column temperature was 25 ℃; the detection wavelength was 278 nm. The number of theoretical plates is not less than 100000 calculated according to phillyrin peak.

Preparation of control solutions: taking a proper amount of phillyrin reference substance, precisely weighing, placing into a brown measuring flask, and adding methanol to obtain a solution containing 0.1mg per 1 mL.

Preparation of a test solution: taking the product, grinding, taking about 0.2g, precisely weighing, placing in a conical flask with a plug, precisely adding 20mL of methanol, sealing the plug, weighing, carrying out ultrasonic treatment (power 400W and frequency 40kHz) for 25 minutes, cooling, weighing again, supplementing the loss weight with methanol, shaking up, filtering, precisely weighing 5mL of subsequent filtrate, steaming to near dryness, adding 0.5g of neutral alumina, stirring uniformly, adding into a neutral alumina column (100-200 meshes, 1g, inner diameter of 1-1.5 cm), eluting with 150mL of 70% ethanol, collecting the eluate, concentrating to dryness, dissolving the residue with 50% methanol, transferring into a 10mL volumetric flask, diluting to scale, shaking up, filtering, and taking the subsequent filtrate.

The determination method comprises the following steps: precisely sucking 2 μ L of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring.

Forsythoside A: the measurement is carried out by referring to high performance liquid chromatography (0512 in the four ministry of communications in 2015 pharmacopoeia of China).

Chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; acetonitrile-0.2% formic acid solution (13: 87) is used as a mobile phase; the flow rate is 0.4mL per minute, and the column temperature is 30 ℃; the detection wavelength was 330 nm. The number of theoretical plates is not less than 100000 calculated according to forsythoside A peak.

Preparation of control solutions: taking a proper amount of forsythoside A reference substance, precisely weighing, and adding methanol to obtain solution containing 0.2mg per 1mL (prepared for clinical use).

Preparation of a test solution: grinding the product, precisely weighing about 40mg, placing into a conical flask with a plug, precisely adding 20mL of 70% methanol, sealing the plug, weighing, ultrasonically treating (power 400W, frequency 40kHz) for 30 minutes, cooling, weighing again, supplementing the lost weight with 70% methanol, shaking, filtering, and collecting the subsequent filtrate.

The determination method comprises the following steps: precisely sucking 2 μ L of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring.

TABLE 1

TABLE 2

Note: "/" indicates no item, "+" indicates detectable, and "-" indicates no detection.

TABLE 3

Index (I)	Example 1	Example 2	Example 3	Example 4
					Yield increase of essential oil/%	8.0	6.5	4.7	5.3
Chlorogenic acid content increase%	21.4	20.5	17.8	16.4
					The rate of increase of forsythin/%)	19.6	15.8	19.5	16.1
Percentage increase of forsythoside A content%	8.1	6.5	7.9	5.7

As can be seen from tables 1 to 3, in comparative example 1 and comparative example 3, example 2 and comparative example 4, and example 3 and comparative example 5, the corresponding examples of the indexes such as the volatile oil yield, the chlorogenic acid content, the forsythin content, the forsythiaside A content and the like are all obviously higher than the corresponding comparative examples, and as can be seen from Table 2, the comparative examples 1 to 5 can not detect the honeysuckle volatile oil, while the examples 1 to 4 can detect the honeysuckle and forsythia volatile oil, which shows that the indexes of the honeysuckle-forsythia traditional Chinese medicine formula particles prepared by the preparation method of the invention are obviously superior to the indexes of single honeysuckle formula particles and single forsythia formula particles, and the problem that the honeysuckle is difficult to recover oil can be effectively solved, and the content of effective components in the unit mass of the traditional Chinese medicine formula granules of the honeysuckle-forsythia medicine pair is effectively improved.

As can be seen from examples 1 to 4, the content of the active ingredient per unit mass can be further increased by controlling the respective parameters within appropriate ranges.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.