CN112773883A

CN112773883A - Preparation method of acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea

Info

Publication number: CN112773883A
Application number: CN202011620456.XA
Authority: CN
Inventors: 李贵森; 霍金海; 何翔; 刘华石; 左文丽; 李凤金
Original assignee: DUODUO PHARMACEUTICAL CO LTD
Current assignee: DUODUO PHARMACEUTICAL CO LTD
Priority date: 2020-12-31
Filing date: 2020-12-31
Publication date: 2021-05-11

Abstract

A preparation method of acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea relates to a preparation method of biochemical capsule. The invention aims to solve the technical problem that the acanthopanax biochemical capsule has no obvious effect on dysmenorrheal. The method comprises the following steps: firstly, drying the ligusticum wallichii at 50-80 ℃ and crushing the ligusticum wallichii into fine powder, wherein the water content is controlled to be below 10%; decocting radix Angelicae sinensis, semen Persicae, Glycyrrhrizae radix, and Zingiberis rhizoma for 1-3 times, adding 2-4 times of water for each time, decocting for 1-2.5 hr, filtering, mixing filtrates, spray drying, and collecting medicinal powder; thirdly, drying the acanthopanax extract under reduced pressure and crushing the acanthopanax extract into fine powder; and fourthly, mixing the fine powder and the medicinal powder obtained in the first step to the third step to obtain the medicine. The ligusticum wallichii powder and the acanthopanax extract are not combined with 4 medicinal material extracting solutions of angelica, peach kernel, liquorice and dried ginger, so that the content of one component capable of inhibiting a factor for treating dysmenorrheal in the extracting solutions is increased, and the curative effect of the acanthopanax biochemical medicine on dysmenorrheal treatment is enhanced. The invention relates to the field of preparation of acanthopanax biochemical capsules.

Description

Preparation method of acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea

Technical Field

The invention relates to a preparation method of a biochemical capsule.

Background

Dysmenorrhea is one of the most common gynecological symptoms, and refers to cramp pain, tenesmus, soreness of waist or other general malaise before and after or during menstrual period, which affects daily life and work. The disease cause which may cause dysmenorrhea can be found through the medical history and the examination of the whole body and the local part, and the treatment can be effectively carried out. Dysmenorrhea is classified into primary dysmenorrhea and secondary dysmenorrhea. The primary dysmenorrhea is also called functional dysmenorrhea, and accounts for more than 90% of dysmenorrhea when no obvious lesion of pelvic organs is found through detailed gynecological clinical examination. Secondary dysmenorrhea refers to the marked pathological changes of genital organs, and dark red blood, such as endometriosis, adenomyosis, pelvic inflammatory disease, gynecological tumor, etc. The biochemical capsule is a Chinese medicine for curing the diseases of menstrual period and induced abortion, postpartum qi deficiency and blood stasis induced vaginal bleeding, purple-dark blood colour or blood clot, aching pain of waist and back, spontaneous perspiration, palpitation and short breath, pale tongue, and also with blood stasis point and deep weak pulse. However, the effect of the medicine on dysmenorrhea is not obvious.

Disclosure of Invention

The invention aims to solve the technical problem that acanthopanax biochemical capsule has no obvious effect on dysmenorrheal, and provides a preparation method of acanthopanax biochemical capsule containing a component capable of inhibiting dysmenorrheal.

The preparation method of the acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrheal is carried out according to the following steps:

firstly, drying the ligusticum wallichii at 50-80 ℃, controlling the water content to be below 10%, and crushing the ligusticum wallichii into fine powder with the granularity of 180 mu m;

decocting angelica sinensis, peach kernels, liquorice and dried ginger for 1-3 times, adding water 2-4 times of the total weight of the raw materials for each time of decoction, filtering for 1-2.5 hours, combining filtrates, spray-drying at 108-115 ℃ in a spray tower, pressure-1-3 MPa in the spray tower, 10-12 MPa of spray pressure, 15-18 Hz of high-pressure pump frequency, 1-2 MPa of steam pressure, 155-165 ℃ of air inlet temperature and 105-115 ℃ of air exhaust temperature, and collecting medicinal powder;

thirdly, drying the acanthopanax extract under reduced pressure, and crushing the acanthopanax extract into fine powder with the granularity of 180 mu m;

fourthly, mixing the fine powder and the medicinal powder obtained in the first step to the third step according to the mass ratio of 125:120:150, and encapsulating to obtain the acanthopanax biochemical capsule containing the components capable of inhibiting dysmenorrheal.

The filtrate after extracting the four medicinal materials of the angelica, the peach kernel, the liquorice and the dried ginger is not concentrated any more, and is directly dried by adopting spray drying equipment, so that the production period is shortened, the energy is saved, the spray drying process can be avoided because the ligusticum wallichii powder and the acanthopanax extract are not combined with the 4 medicinal material extracting solutions of the angelica, the peach kernel, the liquorice and the dried ginger, the loss of volatile components in the ligusticum wallichii powder and the acanthopanax extract in the high-temperature spray drying process can be prevented, and the ligusticum wallichii powder and the acanthopanax extract are not combined with the 4 medicinal material extracting solutions of the angelica, the peach kernel, the liquorice and the dried ginger, the content of one component capable of inhibiting a factor for treating dysmenorrhea in the extracting solutions is increased, and the curative effect of.

Drawings

FIG. 1 is a fingerprint of a spray dried sample from experiment one;

FIG. 2 is a fingerprint of a sample dried under reduced pressure in experiment one.

Detailed Description

The technical solution of the present invention is not limited to the following specific embodiments, but includes any combination of the specific embodiments.

The first embodiment is as follows: the preparation method of the acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrheal in the embodiment comprises the following steps:

The second embodiment is as follows: the difference between the first embodiment and the second embodiment is that in the first step, the ligusticum wallichii is dried at the temperature of 60-70 ℃. The rest is the same as the first embodiment.

The third concrete implementation mode: the difference between this embodiment and the first or second embodiment is that in the first step, the cnidium officinale Makino is dried at 65 ℃. The others are the same as in the first or second embodiment.

The fourth concrete implementation mode: the difference between this embodiment and the first to third embodiments is that in the second step, angelica, peach kernel, licorice and dried ginger are decocted for 2 times. The rest is the same as one of the first to third embodiments.

The fifth concrete implementation mode: the difference between this embodiment and one of the first to fourth embodiments is that water in an amount 3 times the total weight of the raw materials is added in each decoction in the second step. The rest is the same as one of the first to fourth embodiments.

The sixth specific implementation mode: the difference between the first embodiment and the fifth embodiment is that in the second embodiment, the decoction is carried out for 2 hours and then the filtration is carried out for times. The rest is the same as one of the first to fifth embodiments.

The seventh embodiment: this embodiment differs from the first to sixth embodiments in that the temperature in the spray tower in the second step is 110.5 ℃. The rest is the same as one of the first to sixth embodiments.

The specific implementation mode is eight: this embodiment is different from the first to seventh embodiments in that the column internal pressure in the second step is-2.1 MPa. The rest is the same as one of the first to seventh embodiments.

The specific implementation method nine: the present embodiment is different from the first to eighth embodiments in that the spraying pressure in the second step is 11.89 MPa. The rest is the same as the first to eighth embodiments.

The detailed implementation mode is ten: this embodiment is different from one of the first to ninth embodiments in that the vapor pressure in the second step is 1.14 MPa. The rest is the same as one of the first to ninth embodiments.

The following experiments are adopted to verify the effect of the invention:

experiment one:

firstly, drying the ligusticum wallichii at 65 ℃, controlling the water content to be 8 percent, and crushing the ligusticum wallichii into fine powder with the granularity of 180 mu m;

decocting angelica sinensis, peach kernel, liquorice and rhizoma zingiberis for 3 times, adding water which is 4 times of the total weight of the raw materials for each time, filtering for 2.5 hours, combining filtrates, spray-drying at the conditions of the temperature of 110.5 ℃ in a spray tower, the pressure of-2.1 MPa in the spray tower, the spray pressure of 11.89MPa, the high-pressure pump frequency of 17.5Hz, the steam pressure of 1.14MPa, the air inlet temperature of 160.5 ℃ and the air exhaust temperature of 110.4 ℃, and collecting medicinal powder;

Comparison of fingerprint patterns of different drying modes

1. Experimental Material

1.1 Instrument and Equipment for Process

Spray drying apparatus

Decompression drying equipment

1.2 Instrument for testing

An electronic balance: BSA224S-CW type (parts per million) Saedodes scientific instruments, Inc

High performance liquid chromatograph: shimadzu 20AT

A chromatographic column: kromasil 100-5-C18 column

1.3 samples and reagents

Acanthopanax senticosus biochemical capsule decompression drying sample (batch number:) acanthopanax senticosus biochemical capsule spray drying sample (batch number:)

Ligustilide (RFS-G01001909016)

The methanol and the phosphoric acid are both chromatographically pure, and other organic reagents are analytically pure.

2. Two drying methods for sample fingerprint inspection

In order to further analyze the influence of the drying mode on the effective components, the fingerprint spectrum method of the acanthopanax biochemical capsule is adopted to investigate samples of two drying modes, and the method and the result are as follows:

2.1 chromatographic conditions and System suitability test

Using octadecylsilane chemically bonded silica as filler, and using Kromasil 100-5-C18 column (25 cm in column length, 4.6mm in column inner diameter, 5 μ M in particle diameter, M05CLA 25/E167539); using methanol as mobile phase A and 0.1% phosphoric acid as mobile phase B, and performing gradient elution according to the specification in the following table; the detection wavelength is 230 nm; the column temperature was 35 ℃; the flow rate was 0.8ml per minute.

TABLE 1 gradient elution conditions

2.2 preparation of test solutions

Precisely weighing 1g of acanthopanax biochemical capsule content capable of inhibiting dysmenorrhea, placing into a conical flask with a plug, adding 25mL of 50% methanol, weighing, ultrasonically treating for 30min, cooling, supplementing 50% methanol to zero gravity, shaking, filtering, and collecting filtrate.

2.3 assay

Precisely sucking 10 μ l of the test solution, injecting into a liquid chromatograph, measuring, and recording 65 min chromatogram.

As a result: in the chromatogram of the test sample, the chromatographic peak area of ligustilide (peak 1) in spray drying mode is larger than that in reduced pressure drying mode.

TABLE 2 sample Peak areas for different drying regimes

Second, different drying methods contain the radix Acanthopanacis Senticosi biochemical capsule mouse dysmenorrheal experiment that can inhibit dysmenorrheal ingredient

2.1 Experimental animals

The unmated SPF SD rat, female, with the weight of 180-. Adaptive feeding for one week. All animal experiments were approved by the animal ethics committee of the academy of science of traditional Chinese medicine of Heilongjiang province, number 202001010.

2.2 Experimental reagents

Estradiol benzoate injection (ningbo second hormone plant, lot 190516); oxytocin injection (Shanghai Hefeng pharmaceutical Co., Ltd., lot number 09191007) estradiol, progesterone, interleukin-1 beta, interleukin-18, prostaglandin E2, and prostaglandin 2a determination kit (Nanjing institute of bioengineering, lot numbers are 20200805);

2.3 Main Instrument

MIKRO 220R type low temperature high speed centrifuge (Hettich, Germany). Electric homogenizer, ultra-low temperature refrigerator.

2.4 preparation of Primary dysmenorrhea model

The rat model of primary dysmenorrhea was prepared by subcutaneous injection of estradiol benzoate in combination with intraperitoneal injection of oxytocin. Except for the blank group, the rats in each group were injected subcutaneously with estradiol benzoate injection (0.5 mg on days 1 and 10; 0.2mg on days 2 to 9) in the dorsal region. The interval of the last injection is 24h, and the abdominal cavity of each group of rats is injected with oxytocin and 2U. The number of wriggling times is increased remarkably within 30min, which indicates that the model is successfully prepared.

2.5 animal grouping and administration

40 SD rats were randomly divided by weight into a Acanthopanax gracilistylus biochemical capsule reduced pressure drying process group, a Acanthopanax gracilistylus biochemical capsule spray drying process group, a model group and a blank control group (equal volume of distilled water), and 10 rats were each group. The two groups of rats of the acanthopanax biochemical capsule start to be administered by intragastric administration on the 5 th day of molding, and are administered for 7 days; the intragastric volume of each group is 10 ml.kg < -1 >. 30min after the last administration, oxytocin is injected into abdominal cavity to induce dysmenorrhea model.

2.6 number of turns observation

After the oxytocin is injected into the abdominal cavity, the body writhing times and the incubation period of each group of rats within 30min are observed and recorded.

2.7 Biochemical index detection

After the last administration, blood was collected from the abdominal aorta after anesthesia, and serum was separated, and then separately stored by freezing. Separating uterus tissue, freezing in liquid nitrogen at medium speed, and freezing in refrigerator at-80 deg.C. 0.5g of uterine tissue is taken, 4.5ml of precooled PBS is added, an electric homogenizer is used for homogenate, 3000rpm & min < -1 > is carried out, centrifugation is carried out for 10min, and separated supernatant is frozen and stored. Measuring the contents of E2, PROG, IL-1 and IL-18 in serum by using an enzyme linked immunosorbent assay kit according to the operation of a specification; the tissue homogenates were assayed for PGF2a and PGE2 content.

The experimental results are as follows:

2.8 Effect of body writhing frequency and latency in rats of each group

As shown in table 3, the number of writhing times of the model group rats was significantly increased and the writhing latency was significantly shortened, compared to the blank group). Compared with the model group, compared with the acanthopanax biochemical spray drying group and the reduced pressure drying group, the twisting times are reduced, and the reduction of the spray drying group is more obvious.

TABLE 3 influence of writhing frequency and latency in rats: (

n＝10)

2.9 Effect of estrogen level and inflammatory factor content in serum of rats in each group

As shown in Table 4, the serum levels of E2, IL-1 and IL-18 were significantly increased and the PROG content was significantly decreased in the rats of the reduced pressure-dried group, the spray-dried group and the model group, as compared with the blank group. Compared with the model group, the mouse serum contents of E2, IL-1 and IL-18 in the decompression drying group and the spray drying group are all obviously reduced, and the PROG content is obviously increased. Compared with the reduced pressure drying group, the E2, IL-1 and IL-18 contents of the spray drying group are all increased, and the PROG content is reduced.

TABLE 4 influence of Acanthopanax senticosus biochemical capsule containing ingredients capable of inhibiting dysmenorrhea on estrogen level and inflammatory factor content in serum of rats of each group: (

n＝10)

2.10 PGF in uterine tissue of rats in groups_2aAnd PGE₂Influence of content

As shown in Table 5, PGF in the uterus of rats in the model group, the reduced pressure-dried group, and the spray-dried group was compared with that in the blank group_2aThe content is obviously increased, and the content of PGE2 is obviously reduced. PGF in uterus of rats in reduced pressure-dried group, spray-dried group, compared with model group_2aThe content is obviously reduced, and the content of PGE2 is obviously increased. PGF in uterus of spray-dried rats compared to the reduced pressure-dried group_2aThe content is reduced, and the content of PGE2 is increased.

TABLE 5 Acanthopanax senticosus biochemical capsule for PGF in uterine tissue of rats of each group_2aAnd PGE₂Content influence (x ± s, n ═ 10)

Claims

1. The preparation method of the acanthopanax biochemical capsule containing the ingredients capable of inhibiting dysmenorrheal is characterized in that the preparation method of the acanthopanax biochemical capsule containing the ingredients capable of inhibiting dysmenorrheal is carried out according to the following steps:

decocting angelica sinensis, peach kernels, liquorice and dried ginger for 1-3 times, adding water 2-4 times of the total weight of the raw materials for each time of decoction, filtering for 1-2.5 hours, combining filtrates, spray-drying at 108-115 ℃ in a spray tower, -1-3 MPa of pressure in the spray tower, 10-12 MPa of spray pressure, 15-18 Hz of high-pressure pump frequency, 1-2 MPa of steam pressure, 155-165 ℃ of air inlet temperature and 105-115 ℃ of air exhaust temperature, and collecting medicinal powder;

2. The method for preparing the acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein the ligusticum wallichii franchet is dried at 60-70 ℃ in the first step.

3. The method for preparing the acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein the ligusticum wallichii is dried at 65 ℃ in the first step.

4. The method for preparing Wujia Biochemical Capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein in step two, Angelica sinensis, semen Persicae, Glycyrrhiza uralensis and Zingiberis rhizoma are decocted for 2 times.

5. The method for preparing acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein water in an amount of 3 times of the total weight of the raw materials is added in each decoction in the second step.

6. The method for preparing Wujia Biochemical Capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein in step two, decocting for 2h, and filtering for several times.

7. The method for preparing acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein the temperature in the spraying tower in the second step is 110.5 ℃.

8. The method for preparing the acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein the pressure in the tower in the second step is-2.1 MPa.

9. The method for preparing acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein the spraying pressure in step two is 11.89 MPa.

10. The method for preparing acanthopanax biochemical capsule containing ingredients capable of inhibiting dysmenorrhea according to claim 1, wherein steam pressure in step two is 1.14 MPa.