WO2019227885A1

WO2019227885A1 - Capsule preparation of achyranthes aspera l. var. rubrafusca (wight) hook polysaccharide, preparation method, and applications

Info

Publication number: WO2019227885A1
Application number: PCT/CN2018/119440
Authority: WO
Inventors: 徐寒梅; 戚微岩; 董瑶
Original assignee: 安徽德馨华海生物科技有限公司
Priority date: 2018-05-30
Filing date: 2018-12-06
Publication date: 2019-12-05
Also published as: CN110548042A

Abstract

A capsule preparation of an Achyranthes aspera L. var. rubrafusca (Wight) Hook polysaccharide, a preparation method for same, and applications thereof. The capsule preparation comprises an Achyranthes aspera L. var. rubrafusca (Wight) Hook extract and an excipient. The monosaccharide structural units of the Achyranthes polysaccharide are fructose and glucose.

Description

[Corrected 17.12.2018 according to Rule 26] A kind of Yunsi knee polysaccharide capsule preparation, preparation method and application

Technical field

The invention relates to the field of pharmaceutical preparations, in particular to a cloud achyranthes bidentata polysaccharide capsule pharmaceutical preparation, a preparation method and application thereof.

Background technique

Polysaccharides are an important class of macromolecules in the body. In addition to storing energy and supporting structures, they are also a class of important information molecules that play a role in transmitting information in the body. In recent years, people have discovered some polysaccharides such as Poria polysaccharide, Lycium barbarum polysaccharide, and Lentinan polysaccharide, which can repair diseases caused by the damage of the immune system, and have no toxic and side effects, and can be developed into immunomodulators. Therefore, the development of polysaccharides into drugs has a good market prospect.

Achyranthes (Bchyuridae) belongs to the family Polygonaceae, a perennial herbaceous plant, and is one of the major Chinese medicinal materials commonly used in China. Achyranthes was first recorded in the "Shen Nong's Materia Medica". Tao Hongjing explained that "its stems have knots like Achyranthes bidentata", that is, the name of the medicine is derived from the synonymous meaning. Achyranthes bidentata (BI) is a plant belonging to the genus Achyranthes, also known as Hundredfolds, Achyranthes bidentata, chicken bone, is a perennial herb that is rooted into medicine; Cyathula officinalis (Kuan) is also a pupae family , But it is a perennial herb of the genus Calico, also used as a medicine. Both are commonly used in traditional Chinese medicine, and belong to different genera of the same family. According to the records of "Shen Nong's Herbal Classic", Achyranthes bidentata originated from the Han Dynasty, and after several generations of evolution, there have been many varieties such as Achyranthes bidentata, Sichuan Achyranthes bidentata, native Achyranthes bidentata, hemp achyranthes bidentata, and white Achyranthes bidentata.

In the 2015 edition of the Chinese Pharmacopoeia, Achyranthes bidentata was classified into Achyranthes bidentata and Sichuan Achyranthes bidentata. Achyranthes bidentata is bitter, sour, flat, and has the effects of nourishing liver and kidney, strengthening bones and bones, passing blood stasis, and passing blood down; Sichuan Achyranthes bident is sweet, slightly bitter, and flat, with stasis removing, menstrual joint, diuretic The effect of Tonglin. In the grass section of Li Shizhen's Compendium of Materia Medica, Achyranthes bidentata is also known as ox stalk, hundred times, mandrill, and paired vegetables. Among them, there are attached formulas: "Achyranthes bidentata is the medicine of foot jue yin and shao yin. The medicine of the owner is that the wine can nourish the liver and kidney, and the raw material can remove the blood, only the two. It cures waist and knee Bone pain, foot and yin elimination, drowning, prolonged malaria, and low-injury diseases, but not for its liver and kidney benefits? Its treatment symptoms, heart and abdominal pain, bloated and malignant sore, golden sore injury, throat Teeth, sore throat, hematuria, menstrual symptoms, and fetal birth diseases are not the only way to remove the evil blood? "Therefore, the research on Achyranthes bidens has existed since ancient times.

There are many main components of Achyranthes bidentata, including triterpenoid saponins, sterones, polysaccharides, and alkaloids. Achyranthes bidentata polysaccharide is a kind of polysaccharide extracted from the root, which is one of the effective components of Achyranthes bidentata. Because it has the advantages of small molecular weight, good water solubility, low toxicity, etc., which is conducive to better development and utilization, it can be developed into medicine or health food, and has good market prospects.

Pregnant with achyranthes, Chinese name is Achyranthes bidentata, and its Latin name is Achyranthes aspera. Cloud Achyranthes, Latin name Achyranthes aspera L.var.rubrafusca (Wight) Hook. From this Latin name, it can be seen that Achyranthes bidentata is a variant of Achyranthes bidentata, which is an endemic plant in Yunnan. At present, its chemical composition and pharmacological effects have not been reported. Polysaccharide from stem and leaf of Achyranthes bidentata is a kind of polysaccharide extracted from the stem and leaf of Achyranthes bidentata.

The drugs in the capsules are directly filled in the powder or granules in the capsule shell and are not affected by factors such as tablet pressure, so they can be quickly dispersed, dissolved and absorbed in the gastrointestinal tract, and their bioavailability is higher than that of tablets. In addition, capsules can also isolate the drug from moisture, air, and light, thereby improving the stability of the drug.

However, when the filling in the capsule is easy to absorb moisture, the content powder is prone to agglomeration, which affects the dissolution rate of the drug and reduces the bioavailability. In addition, the moisture absorption of the capsule contents will cause the capsule shell to become brittle and affect the quality of the capsule. Due to its strong water solubility and its hygroscopicity, it is necessary to find suitable excipients and their dosages to ensure the stability and effectiveness of polysaccharides from Yunzhi.

Relevant investigations were performed on the raw material of Achyranthes bidentata. The properties and hygroscopicity of polysaccharide extract of Achyranthes bidentata are shown in Table 1 under the environment of room temperature and relative humidity of 75% for 7 days.

Table 1 Properties and hygroscopicity of Achyranthes bidentata polysaccharide extract

From the results of the investigation, it can be known that the drug substance has strong hygroscopicity. In order to ensure the stability of the granules made, it is necessary to add excipients with good moisture resistance. Through a large number of experiments, the present invention finds that the extract of Achyranthes bidentata polysaccharides, the granulation method, the types of excipients, the proportion of excipients, the concentration of solvents, etc. will affect its moisture-proof effect.

Microcrystalline cellulose (MCC), also known as wood powder, microcrystalline, cellulose, etc., is a free-flowing, very fine, short rod-shaped or natural free-flowing cellulose that has been hydrolyzed to the limit degree of polymerization (LOOP) by dilute acid. Powdery porous particles, white, odorless, odorless, composed of porous particles. Microcrystalline cellulose is often used as an adsorbent, suspending agent, diluent, and disintegrant. Microcrystalline cellulose is widely used in pharmaceutical preparations. It is mainly used as a diluent and binder in oral tablets and capsules. It can be used not only for wet granulation but also for dry direct compression. There is also a certain lubricating and disintegrating effect.

The molecular formula of the fine powder silica gel is: mSiO ₂ -nH ₂ O. Its physical and chemical properties are: non-toxic, odorless, non-combustible, non-explosive, non-volatile, non-corrosive, large pore volume, and strong surface activity. It is a very fine powder of silicon dioxide. Because it has a small bulk density and a very loose texture, it is mainly used as a glidant. After use, it is mainly filled between particles to isolate the interfitting between particles.

Different polysaccharides have different structure and composition, so the selected excipients are different. At present, there is no literature report on the preparation of polysaccharides from Achyranthes bidentata.

Therefore, based on Yun hyssop ’s polysaccharide raw material medicine, its hygroscopicity is very strong. For example, there is a problem of poor stability and effectiveness of the preparation of the drug. However, there is a problem in the development of Yun Ginkgo ’s polysaccharide drug in the prior art. Knee polysaccharide capsule medicine preparation, preparation method and application.

Summary of the Invention

1. Problems to be solved

Aiming at the problem of hygroscopicity of the raw material medicine of Achyranthes bidentata polysaccharide, such as the problems of poor stability and effectiveness of the preparation of the drug, and the lack of development of the medicine of Achyranthes bidentata polysaccharide in the prior art, the present invention provides a cloud of Achyranthes bidentata polysaccharide. Polysaccharide capsule pharmaceutical preparation, preparation method and application.

2. Technical solution

To solve the above problems, the technical solutions adopted by the present invention are as follows:

The invention provides a cloud achyranthes polysaccharide capsule preparation. The preparation includes a cloud achyranthes polysaccharide extract and an excipient. The purified monosaccharide structural units of the cloud achyranthes polysaccharide extract are fructose and glucose.

As a further improvement of the present invention, the auxiliary materials include fillers, binders, and lubricants, and the fillers are lactose, microcrystalline cellulose, soluble starch, dextrin, corn starch, sorbitol, and mannitol. One or more of calcium sulfate, calcium hydrogen phosphate, calcium carbonate; the lubricant is one or more of magnesium stearate, micronized silica gel, talc, and stearic acid; the binder It is one or more of water, starch slurry, ethanol, povidone, ethyl cellulose, and gelatin.

As a further improvement of the present invention, the formulation excipient composition is: dextrin + micron silica gel, dextrin + MCC + micron silica gel, corn starch + magnesium stearate, cornstarch + MCC + micron silica gel, soluble starch, soluble starch + MCC , Soluble starch + MCC + micro powder silica gel, soluble starch + magnesium stearate, MCC, MCC + micro powder silica gel, MCC + magnesium stearate.

As a further improvement of the present invention, the content of the polysaccharide extract of Achyranthes bidentata accounts for 20% to 80% of the content of the preparation, and the content of auxiliary materials accounts for 20% to 80% of the content of the preparation.

As a further improvement of the present invention, the mass percentage of the filler to the excipients is 95% to 99%, the mass percentage of the binder to the excipients is 0 to 10%, and the mass percentage of the lubricant to the excipients is 0, respectively. ~ 5%.

As a further improvement of the present invention, the formulation is:

Polysaccharide from Achyranthes bidentata 50%;

Microcrystalline cellulose 47%;

Micronized silica gel 3%.

As a further improvement of the present invention, the formulation is:

As a further improvement of the present invention, the preparation is filled with powder or granules during the preparation process. The preparation method of filling the capsule preparation with powder includes the following steps:

(1) The auxiliary materials are pulverized with an ultra-fine pulverizer to an average particle size of <50 μm, and the cloud achyranthes polysaccharide is sieved through a 60-120 mesh sieve for future use;

(2) Weigh the prescription amount of Achyranthes bidentata polysaccharides and auxiliary materials in a mixing granulator, set the stirring speed and chopping speed, and mix for 10 minutes;

(3) Take the mixture in step (2), and fill the capsule shell with the amount of (0.2g-0.8g) ± 10% / capsule;

(4) Check the finished product of the capsule, the appearance should be neat, without sticking, deformation or cracking; the content is dry, and the moisture content is controlled below 4%; the difference in the loading amount, uniformity of content, disintegration and Dissolution

(5) Carry out corresponding packaging;

(6) Storage.

As a further improvement of the present invention, the preparation method for filling the capsule preparation into granules includes the following steps:

(2) Weigh the auxiliary materials and add them to the wet mixing granulator, set the stirring speed and chopping speed, mix for 10 minutes, add an appropriate amount of binder to make the soft material, and pass the soft material through a 20 mesh sieve to make wet particles. Wet granules are dried at 60 to 70 ° C for 50 to 60 minutes. Dry granules are sized with a 20-mesh sieve to obtain blank granules;

(3) Prepare a 10% ethanol solution of Achyranthes bidentata polysaccharide 1) Mix the above solution in a fine powder of blank particles (below 30 mesh), pass through a 20 mesh sieve twice, and dry at 60 to 70 ° C for 50 to 60 minutes. Mix with the blank particles prepared in step (2); 2) spray the solution onto the surface of the blank particles and dry in time;

(4) Take the mixture in step (3), and fill the capsule shell with a loading of (0.2g-0.8g) ± 10% / capsule;

(5) Check the finished product of the capsule, the appearance should be neat, without sticking, deformation or cracking; the content is dry, and the moisture content is controlled below 4%; the difference in loading amount, content uniformity, disintegration and Dissolution

(5) Carry out corresponding packaging;

(6) Storage.

As a further improvement of the present invention, the preparation method of the cloud achyranthes bidentata polysaccharide capsule preparation, the granulation process of the preparation in the preparation process is wet granulation or directly mixed without granulation.

As a further improvement of the present invention, the capsule preparation is used for preparing health-enhancing foods of enhanced immunity type, liver protection type and hypoglycemic type.

As a further improvement of the present invention, the capsule preparation is used for preparing medicines of enhanced immunity type, liver protection type and hypoglycemic type.

3. Beneficial effects

Compared with the prior art, the beneficial effects of the present invention are:

(1) The cloud achyranthes bidentata polysaccharide capsule pharmaceutical preparation of the present invention prepares cloud achyranthes bidentata polysaccharide extract (cloud achyranthes bidentata polysaccharide) into a capsule form, on the one hand, it overcomes the poor fluidity of the cloud achyranthes bidentata polysaccharide powder, It is extremely easy to absorb moisture, increase the viscosity after moisture absorption, and make it difficult to produce and store. On the other hand, it can significantly mask the unpleasant smell of the drug, accelerate disintegration, improve the absorption effect, improve bioavailability and stability, and control the dose of the drug. , Easy to take, carry and hide the effect, which is conducive to promotion.

(2) The pharmaceutical preparation of polysaccharide capsule of Achyranthes bidentata according to the present invention is composed of excipients: dextrin + micron silica gel, dextrin + MCC + micron silica gel, corn starch + magnesium stearate, cornstarch + MCC + micron silica gel, soluble starch, Soluble starch + MCC, soluble starch + MCC + micron silica gel, soluble starch + magnesium stearate, MCC, MCC + micron silica gel, MCC + magnesium stearate; Compared with the compatibility of related polysaccharides in the prior art, it is more Can effectively improve the hygroscopic properties of the raw material medicine Achyranthes bidentata. The screening of excipients of the cloud achyranthes polysaccharide capsule according to the present invention is an excipient screening based on the structure and composition of the cloud achyranthes polysaccharide, and the final preparation has stable properties.

(3) The cloud achyranthes bidentata polysaccharide capsule pharmaceutical preparation of the present invention provides a capsule dosage form of cloud achyranthes bidentata polysaccharide whose structural unit is glucose and fructose, which is convenient to take. It fills the blank of this type of polysaccharides in the research of preparations, and provides more space for the medicinal value development of polysaccharides from Achyranthes bidentata.

(4) The preparation method of the Yun Achyranthes bidentata polysaccharide capsule pharmaceutical preparation of the present invention has good filling fluidity, uniform content, simple production process, good reproducibility, and meets the requirements of large-scale industrialization.

(5) The application of the cloud achyranthes bidentata polysaccharide capsule pharmaceutical preparation, which has obvious effects on immune regulation, liver protection, hypoglycemia, and antitumor, etc. Patients and other groups have the health-care effect of physical fitness, the quality of the preparation is stable, which is conducive to popularization.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph of hygroscopicity of a prescription in Example 6 of the present invention;

FIG. 2 is a graph of hygroscopicity of a prescription in Example 7 of the present invention; FIG.

Fig. 3 is a graph showing the hygroscopicity of the prescription of the present invention and the polysaccharide prescription of the prior art.

Detailed ways

The present invention is further described below with reference to specific embodiments.

Example 1

This example is a study on the extraction process and structure identification of Achyranthes bidentata polysaccharide (AAP). The extraction method of Achyranthes bidentata (AAP) includes the following steps:

1) Test method: Weigh 20g of dried yunnan achyranthes stems and leaves in 3 parallel portions, add distilled water to the beaker, heat for half an hour, adjust the pH to 8-9 (that is, extract with alkaline water), and heat extract with water bath Stir once every 10 min, take the supernatant, and suction filter to concentrate to 1/20 of the original volume. Precipitate with 4 times the volume of absolute ethanol, leave it in a refrigerator at 4 ° C overnight, centrifuge in a high-speed refrigerated centrifuge for 10 min (10000 rpm), take the precipitate and dissolve it, and then remove the protein with Sevag (chloroform: n-butanol = 5: 1) reagent, vigorously After stirring, it was centrifuged for 10 min (10000 rpm), repeated 4 times and concentrated; freeze-dried under vacuum to obtain crude AAP, weighed and stored for future use. Anthrone-sulfuric acid method was used to detect the polysaccharide content.

2) Optimization of AAP extraction conditions

Because the polysaccharide content obtained by the non-optimized extraction method was low, the L ₉ (3 ³ ) orthogonal test design was used to optimize the extraction conditions of AAP. Three factors were selected: material-liquid ratio, extraction temperature, and extraction time. Each factor was selected at three levels. Each group took 10g of dried Yunshan knee stalks and leaves;

Table 2 Factors and levels of orthogonal test for extraction conditions

3) The effect of the number of extractions on the yield of AAP

Take 20g of dried Yunshan knee stem and leaf fine sections, according to the optimal extraction conditions obtained by orthogonal experiments, the extraction temperature is 80 ° C, the material-liquid ratio is 1:20, and the extraction time is 2h. The extraction is performed once, twice, and three times. Each extraction solution was concentrated, lyophilized, and weighed to obtain crude AAP. The polysaccharide content was measured by anthracene sulfate method. The effect of the number of extractions on the yield of AAP was obtained by comprehensively considering economic factors.

The test results obtained by this method are as follows:

1) Investigation results of optimization of AAP extraction conditions

The polysaccharide yield is calculated according to the following formula:

Polysaccharide yield (%) = Polysaccharide amount of stem and leaf of Achyranthes bidentata (Wi) / Amount of raw material of stem and leaf of Achyranthes bidentata (W) × 100%

Considering the yield of polysaccharides from stems and leaves of Achyranthes bidentata and the polysaccharides, the optimal combination of extraction conditions was a material-liquid ratio of 1:20, an extraction temperature of 80 ° C, and a time of 2 hours. After half an hour, the pH was adjusted to 8-9, and the extraction was continued. The content of polysaccharide detected by anthrone sulfate method was 62.67%, and the yield was 9.02%. The effects of extraction conditions orthogonal test on polysaccharide content and yield are shown in Table 3.

Table 3 Effect of extraction conditions orthogonal test on polysaccharide content and yield

2) The effect of extraction times on the yield and content of AAP

The effect of the number of extractions on the yield and content of polysaccharides from the stems and leaves of P. yunnanensis is shown in Table 4.

Table 4 Effects of extraction times on the yield and content of polysaccharides from the stems and leaves of P. yunnanensis

It can be seen from the above tests that the process conditions are: material-liquid ratio 1:20, extraction temperature 80 ° C, time 2h; adjust the pH to 8-9 after half an hour of extraction, and continue to extract; extract once or twice. Extraction of polysaccharide content is sufficient.

The polysaccharide extracted from the extraction conditions was purified. The purified polysaccharide from Achyranthes bidentata was confirmed by structure to include monosaccharides including glucose and fructose, and the molecular weight was 1 to 3 kD. Its basic structural unit is:

Among them, n ₁ = 0 to 6, n ₂ = 0 to 3, and n ₃ = 0 to 3.

The pharmacological test of the polysaccharide showed that the structure of the polysaccharide has excellent immune activity, hypoglycemic activity and hepatoprotective activity.

Example 2

This embodiment is an embodiment of screening auxiliary materials according to wet granulation. The raw material drug in this example is the unpurified polysaccharide of Achyranthes bidentata in Example 1.

The screening auxiliary materials in this embodiment include:

Fillers: lactose, microcrystalline cellulose, soluble starch, dextrin, corn starch, sorbitol, mannitol, calcium sulfate, calcium hydrogen phosphate, calcium carbonate; lubricants: magnesium stearate, micronized silica gel, talc, hard Fatty acid.

experiment procedure

1) Determination of moisture absorption percentage

The glass dryer with the supersaturated sodium chloride solution at the bottom was placed at room temperature for 24 hours, and the relative humidity in the dryer was 75%. Screen the excipients with the ratio of API: excipient drug to 1: 1, put about 2mm granules on the bottom of the weighing bottle dried to constant weight, accurately weigh them and place them in a glass desiccator at 12, 24, 48, Weigh the mass after 60, 72, 108, 120, 144, and 168 hours, and observe whether the color of the medicine powder changes or not, and whether there is agglomeration.

2) Regression analysis of moisture absorption data

The hygroscopic time curve of traditional Chinese medicine extract is similar to the left half of the univariate quadratic equation y = ax ² + bx + c (a <0). Therefore, the hygroscopic time curve data of each sample is binomially regression processed to obtain the hygroscopic two Term equation: y = at ² + bt + c, derivative r = dw / dt = 2at + b, derivative: r ² = dr / dt = 2a, where y-hygroscopicity, t-time, r-hygroscopic Velocity, r ² -hygroscopic acceleration, abc- constant.

Experimental results

In this embodiment, the excipients are screened based on the ratio of API to excipients of 1: 1, and the hygroscopic curve of different excipients mixed with drugs is regression processed, and the appearance of the drug is recorded. See Table 5.

Table 5 Hygroscopicity equation of Achyranthes bidentata polysaccharide extract compatible with various excipients for wet granulation

Example 3

This embodiment is a screening of the concentration and amount of the wet granulated binder. The raw material medicine in this example is the unpurified polysaccharide of Achyranthes bidentata in Example 1.

With the molding rate and the granulation effect as the indicators of investigation, the appropriate binder concentration and amount were selected. The adhesives screened in this embodiment are: water, starch slurry, ethanol, povidone, ethyl cellulose, and gelatin.

Investigation of the amount of binder The granulation is the ratio of the amount of added binder (mL) to the total amount of raw materials and auxiliary materials, the calculation formula is as follows:

Binder dosage ratio (%) = added amount (mL) / (raw material + auxiliary materials) * 100%

(1) Determination of the types of binders: the fixed main and auxiliary materials are added at a ratio of 1: 1, each serving is 0.5g of raw materials and 0.5g of auxiliary materials, granules are made with different kinds of binders, and the granulation state of different kinds of binders The impact is shown in Table 6.

Table 6 Effects of different types of binders on the granulation state

(2) Determination of the concentration of the binder: The ratio of fixed main and auxiliary materials is 1: 1, and each serving is 0.5g of API and 0.5g of auxiliary materials. Of additives on the granulation effect and hygroscopicity of materials. See Table 7 for the granulation effect of different concentration binders.

Table 7 Granulation effect of binders with different concentrations

(3) Determination of the added amount of the binder: the main and auxiliary materials are added in a ratio of 1: 1, and different amounts of the binder with a concentration of 80% are added as the binder, and the drying conditions are 60 ° C. and the time is 20 minutes. The effect of the added amount of the binder on the granulation effect of the materials was studied. See Table 8 for the granulation effect of different amounts of binder.

Table 8 Effects of different dosages of binders on granulation of materials

From the above results, it can be seen that the binder may be one or more of water, starch syrup, ethanol, povidone, ethyl cellulose, and gelatin. Among them, the granulation effect of ethanol is the best. From the perspective of granulation, the dosage ratio of 80% ethanol is about 40%, which satisfies the principle of "holding it into a mass and pressing it lightly".

According to the results of the above research, the excipient formula of the Yunsi knee polysaccharide capsule medicine can be:

Excipient Formula 1:

Filler 95%;

Lubricant 5%;

Granulation without a binder.

Excipient Formula 2:

Filler: 99%;

Lubricant 1%;

The amount of binder granulation is 10%.

Excipient Formula 3:

Filler: 99%;

Lubricant 0%;

The amount of binder granulation is 5%.

Example 4

This embodiment is an embodiment of directly mixing the auxiliary materials and screening the auxiliary materials without a granulation method. The raw material medicine in this example is the unpurified polysaccharide of Achyranthes bidentata in Example 1.

The screening auxiliary materials in this embodiment are: fillers: lactose, microcrystalline cellulose, soluble starch, dextrin, corn starch, sorbitol, mannitol, calcium sulfate, calcium hydrogen phosphate, calcium carbonate; lubricants: magnesium stearate, Micronized silica gel, talc, stearic acid.

Experimental procedure: Basically the same as that of Example 2.

Experimental results

The hygroscopic curves of different adjuvants and drugs were regressed, and the appearance and shape of the drugs were recorded. The results of the hygroscopic equation of the cloud achyranthes polysaccharide extract mixed with each adjuvant are shown in Table 9.

Table 9 Hygroscopicity equation of Achyranthes bidentata polysaccharide extract mixed directly with various excipients

Example 5

This example is for the determination of hygroscopicity of raw and auxiliary materials in mixed capsules. The raw material medicine in this example is the unpurified polysaccharide of Achyranthes bidentata in Example 1.

Cloud achyranthes bidentata polysaccharide powder has poor fluidity, is extremely hygroscopic, and the viscosity increases after moisture absorption, which causes difficulties in production and storage, and affects disintegration in the body. In order to conceal the unpleasant smell of the drug, accelerate disintegration, improve absorption effect, improve bioavailability and stability, and achieve a controlled dose of the drug, which is convenient for taking, carrying and hiding, this product is made into capsules.

According to the requirements of the capsule molding process and the characteristics of this product, in order to improve the flowability, moldability, adhesion, moisture absorption resistance and disintegration of the capsules, on the other hand, it is necessary to ensure that the difference in the volume of the packaging is in line with the requirements. Filling the powder into the capsule shell requires granulating the powder or adding auxiliary materials such as fillers, binders, disintegrating agents, and lubricants, mixing the medicinal powder with the auxiliary materials, granulating, and then filling.

In this experiment, a better formula was selected in the previous experiments to fill the capsules and determine the hygroscopicity. The experimental procedure for measuring the hygroscopicity is the same as in Example 3. See Table 10 for the hygroscopicity measurement after filling the capsules.

Table 10 Determination of hygroscopicity after filling capsules

Example 6

The drug substance in this embodiment is the unpurified polysaccharide of Achyranthes bidentata in Example 1.

The prescription of Yun Niu Ji Polysaccharide Capsule is:

Polysaccharide from Achyranthes bidentata 50%;

Microcrystalline cellulose 47%;

Micronized silica gel 3%.

The hygroscopicity of the Yunshiu knee polysaccharide capsule pharmaceutical preparation prescription in this example is shown in Table 11.

Table 11 Mapping of hygroscopicity of Achyranthes bidentata polysaccharide capsules in this example

The prescription is made into 1000 capsules, and the content of polysaccharide extract of Achyranthes bidentata in each capsule accounts for 10% of the content of the capsule preparation. The amount of polysaccharide from Achyranthes bidentata in the preparation is 20 mg.

The hygroscopicity ratio of the prescription of Example 6 of the present invention is plotted. Among them, 1 is the raw material medicine of Achyranthes bidentata polysaccharide extract; 2 is a positive control lentinan; : 0.03.

Example 7

In this embodiment, the prescription of the cloud achyranthes polysaccharide capsule pharmaceutical preparation is:

The hygroscopicity of the Yunshiu knee polysaccharide capsule pharmaceutical preparation prescription in this example is shown in Table 12.

Table 12 Raw materials and auxiliary materials

The prescription is made into 1000 capsules, and the content of the polysaccharide extract of Achyranthes bidentata accounts for 60% of the content of the preparation. The content of polysaccharide extract of Achyranthes bidentata in the preparation was 200 mg.

The hygroscopicity ratio of the prescription of Example 7 of the present invention is plotted. Among them, 1 is the extract of Achyranthes bidentata polysaccharide; 2 is a positive control lentinan; 0.5: 0.25: 0.20: 0.05.

Example 8

Polysaccharide from Achyranthes bidentata 80%;

Microcrystalline cellulose 10%;

Dextrin 10%.

The prescription was made into 1000 capsules, and the content of Achyranthes bidentata polysaccharide extract in each capsule was 150 mg.

Example 10

Cloud Achyranthes bidentata polysaccharide extract 20%

Microcrystalline cellulose 79%;

Micronized silica gel 1%.

The prescription was made into 1000 capsules, and the content of Achyranthes bidentata polysaccharide extract in each capsule was 10 mg.

Comparative example

This comparative example is a comparative example in which a hyacinth is mixed with other polysaccharide capsule supplementary materials in the prior art to perform a hygroscopicity test. The drug substance in this embodiment is the unpurified polysaccharide of Achyranthes bidentata in Example 1.

As different polysaccharides have different structures and compositions, the selected excipients are also different. Among them, the compatibility of different polysaccharide types and auxiliary materials in the prior art is shown in Table 13. In this embodiment, the hygroscopicity measurement is performed by using the Achyranthes bidentata polysaccharides in combination with the polysaccharide adjuvants disclosed in the prior art.

Table 13 Compatibility of different polysaccharide types and excipients in the prior art

The hygroscopicity comparison between the prescriptions of the present invention and the polysaccharide adjuvant formulations in the prior art is shown in Table 14. Experimental procedure: Basically the same as in Example 2.

Table 14 Comparison of hygroscopicity between the prescriptions of the present invention and the polysaccharide excipients in the prior art

The research results show that although these adjuvant ratios can improve the hygroscopicity of Achyranthes bidentata polysaccharides to a certain extent, the best formula for improving hygroscopicity is the prescription of the present invention (prescription 9). Raw materials: microcrystalline cellulose: micronized silica gel 0.5: 0.47: 0.03. The selection of excipients in this patent is an excipient screening based on the polysaccharide structure of Achyranthes bidentata.

The moisture absorption curve of the prescription of the present invention and the polysaccharide adjuvant formulation of the prior art is regression processed, and the results are shown in Table 15.

Table 15 Regression processing of hygroscopic curve of the prescriptions of the present invention and the polysaccharide excipients in the prior art

Fig. 3 is a graph showing the hygroscopicity of the prescription of the present invention and the polysaccharide prescription of the prior art. Among them, 1 is the raw material of Achyranthes bidentata; 2 is the raw material: lactose: MCC: CaHPO ₄ = 1: 0.297: 0.503: 0.200; 3 is the raw material: mannitol = 1: 1.5; 4 is the raw material: microcrystalline cellulose: hard Magnesium stearate = 4.1: 1.84: 0.06; 5 as raw material: calcium hydrogen phosphate: cross-linked polyvinyl pyrrolidone = 0.25: 0.05: 0.08; 6 as raw material: maltodextrin: potato flour = 1: 0.5: 0.5; 7 as raw material : Lactose: mannitol = 1: 0.375: 0.125; 8 as raw material: dextrin = 1: 1; 9 as raw material: microcrystalline cellulose: micronized silica gel = 0.5: 0.47: 0.03.

The invention and its implementation have been schematically described above, and the description is not restrictive. Therefore, if a person of ordinary skill in the art is inspired by it and, without departing from the purpose of the present invention, a structural method and an embodiment similar to the technical solution are not creatively designed, all should belong to the protection scope of this patent.

Claims

A cloud achyranthes polysaccharide capsule preparation is characterized in that the preparation comprises a cloud achyranthes polysaccharide extract and an excipient, and the purified monosaccharide structural units of the cloud achyranthes polysaccharide extract are fructose and glucose.
The capsule preparation of Achyranthes bidentata according to claim 1, characterized in that the auxiliary materials include a filler, a binder and a lubricant, and the filler is lactose, microcrystalline cellulose, soluble starch, paste One or more of refined, corn starch, sorbitol, mannitol, calcium sulfate, calcium hydrogen phosphate, and calcium carbonate; the lubricant is one of magnesium stearate, micronized silica gel, talc, and stearic acid Or more; the binder is one or more of water, starch syrup, ethanol, povidone, ethyl cellulose, and gelatin.
The Yun Achyranthes bidentata polysaccharide capsule preparation according to claim 1 or 2, characterized in that the formulation auxiliary material composition is: dextrin + micronized silica gel, dextrin + MCC + micronized silica gel, corn starch + magnesium stearate, corn starch + MCC + micron silica gel, soluble starch, soluble starch + MCC, soluble starch + MCC + micron silica gel, soluble starch + magnesium stearate, MCC, MCC + micron silica gel, MCC + magnesium stearate.
The capsule preparation of Achyranthes bidentata according to claim 3, wherein the mass percentage of the filler in the excipients is 95% to 99%, and the mass percentage of the binder in the excipients is 0 to 10%, respectively; The mass percentage of the lubricant to the auxiliary materials is 0 to 5%, respectively.
The capsule preparation of Achyranthes bidentata according to claim 3, characterized in that the content of the extract of Achyranthes bidentata accounts for 20% to 80% of the content of the preparation, and the content of auxiliary materials accounts for 20% to 80% of the content of the preparation.
The method of claim 1 or 2, wherein the filling method of the preparation in the preparation process is powder or granule.
The method of claim 1 or 2, wherein the granulation process of the preparation in the preparation process is wet granulation or directly mixed without granulation.
The use of the cloud achyranthes bidentata polysaccharide capsule preparation according to claim 1 or 2, characterized in that the capsule preparation is used for preparing health-enhancing foods of enhanced immunity type, liver protection type and hypoglycemic type.
The use of the Yun Achyranthes bidentata polysaccharide capsule preparation according to claim 1 or 2, characterized in that the capsule preparation is used for preparing medicines for enhancing immunity, protecting liver and lowering blood sugar.