CN116850148A

CN116850148A - Forming method for modifying high-viscosity Dajianzhong granule containing maltose

Info

Publication number: CN116850148A
Application number: CN202310794800.4A
Authority: CN
Inventors: 张宁; 朱国琴; 王冰; 王丹丹; 邹纯朴; 江美芳; 邢越阳; 徐洁; 王金峰
Original assignee: Sph Xing Ling Sci & Tech Pharmaceutical Co ltd
Current assignee: Sph Xing Ling Sci & Tech Pharmaceutical Co ltd
Priority date: 2023-06-30
Filing date: 2023-06-30
Publication date: 2023-10-10

Abstract

The invention provides a method for forming particles in a large building, which changes high viscosity containing maltose, and comprises the following steps: directly spray-drying extract of the large-scale middle-building sample containing maltose without adding any auxiliary materials, adding lubricant and auxiliary materials into the obtained extract powder, and performing dry granulation to form particles of the large-scale middle-building sample. The invention also provides an application of the method for forming the high-viscosity large-scale intermediate granule containing maltose in preparing large-scale intermediate granule. The invention further provides a preparation method of the high-viscosity Dajianzhong granule containing maltose and the Dajianzhong granule prepared by the preparation method. The method for forming the granule in the large-scale building with high viscosity containing the maltose has the advantages of simple process operation, small addition amount of auxiliary materials and high drug loading capacity, and effectively solves the problems that the granule is difficult to prepare due to large maltose content in the prescription in the large-scale building.

Description

Forming method for modifying high-viscosity Dajianzhong granule containing maltose

Technical Field

The invention belongs to the technical field of preparation of traditional Chinese medicine components, and relates to a method for forming large-scale Chinese medicinal granule containing maltose with high viscosity.

Background

The Dajianzhong decoction is composed of three medicines of dried ginger, pepper and ginseng, and added with maltose, and is a classical prescription in Jinkui Lloyd from Zhang Zhongjing. The dried ginger in the recipe is pungent and hot, and warms the middle and dispels cold; the pricklyash peel is spicy, hot, dry and strong, warms middle energizer and relieves pain; the ginseng is used together with the ginseng for tonifying middle-jiao and relieving urgency, has the effects of warming middle-jiao and tonifying deficiency, calming adverse-rising energy and preventing vomiting, and relieving urgency and pain, and is mainly used for treating gastric and abdominal severe pain syndrome of middle-jiao weakness and yin cold internal abundance, and is clinically used for treating digestive system diseases in modern times.

The Dajianzhong decoction is used as a classical prescription, is widely applied clinically, has no granule or other dosage forms of products on the market at present in the main clinical application form, but is inconvenient to decoct, take, carry and store in the traditional decoction, so the preparation of the Dajianzhong decoction into granules with stable quality and convenient taking and carrying can overcome the defects.

In the report of the existing preparation method of the Dajianzhong granule, because maltose is not added in the prescription, the viscosity of the extract of the prescription is very low, and the extract is easier to granulate (for example, zhang Haiming and the like are researched on the extraction process of Dajianzhong decoction by adopting a beta-cyclodextrin inclusion process, li Xiang and the like, volatile oil is collected by adopting an inclusion process, then the liquid medicine, dregs and ginseng are decocted, concentrated, added with 5 percent of lactose and inclusion compound for spray drying, and ethanol is added for dry granulation to obtain Dajianzhong granule).

However, in order to keep the granule prepared from classical formula in Dajian consistent with original formula in Zhang Zhongjing, about 100g crude drug in each decoction should be added with maltose up to 200 ml. The maltose is prepared from Oryza Glutinosa or fructus Hordei vulgaris by steaming and fermenting, and has the shape of viscous transparent liquid. The extract of Dajian contains maltose for granulating. However, maltose, also known as maltose syrup or maltose syrup, is known as a starch sugar with the longest production history, and is used as a raw material in modern industry. Therefore, the problem of high viscosity and easy moisture absorption of the extract of the large-scale Chinese medicinal herb containing a large amount of maltose brings great difficulty to the preparation of the large-scale Chinese medicinal herb granules. The prescription of the existing granule in large scale construction contains a large amount of maltose, and the maltose itself has larger viscosity, the relative density is about 1.274-1.285, the solid content is about 74-76%, the melting point is lower about 108 ℃, the hot-melt wall adhesion is easy to be caused, and the maltose powder is easy to absorb moisture after drying, so that the difficulty in the granule preparation process is great, and the granule cannot be obtained by using the conventional drying method and the conventional preparation process.

Disclosure of Invention

In view of the above-mentioned drawbacks of the prior art, the present invention aims to provide a method for forming granules in large-scale buildings, which is capable of changing the viscosity of the granules in large-scale buildings containing maltose, selecting a proper drying mode and adding auxiliary materials in proper proportion to prepare granules with stable quality, so as to solve the problems of difficult drying and difficult preparation forming of granules in large-scale buildings containing maltose in the prior art.

To achieve the above and other related objects, a first aspect of the present invention provides a method for molding particles in a large building for changing high viscosity containing maltose, comprising: directly spray-drying extract of the large-scale middle-building sample containing maltose without adding any auxiliary materials, adding lubricant and auxiliary materials into the obtained extract powder, and performing dry granulation to form particles of the large-scale middle-building sample.

Preferably, the spray drying conditions are: the air inlet temperature is 105-130deg.C, specifically 105-110deg.C, 110-130deg.C, preferably 110deg.C; the liquid inlet speed is 4.0-7.5ml/min, such as 4.0-4.5ml/min, 4.5-7.5ml/min, preferably 4.5ml/min; the atomization pressure is 0.41-1.8bar, such as 0.41-1.35bar, 1.35-1.8bar, preferably 1.35bar.

The spray drying is a technology for obtaining a powdery product by spraying liquid materials with certain concentration into mist droplets by using an atomizer and putting the mist droplets into hot air flow with certain flow velocity to quickly dry the mist droplets, and the obtained powder has good uniformity, fluidity, looseness and solubility, can simplify the production process, and is suitable for the preparation process of traditional Chinese medicine extracts.

Preferably, the lubricant is magnesium stearate.

Preferably, the lubricant is added in an amount of 0.4-0.6% by mass, such as 0.4-0.5%, 0.5-0.6%, preferably 0.5% by mass, based on the mass of the extract powder.

Preferably, the auxiliary material is selected from one of dextrin, soluble starch or lactose, preferably dextrin.

More preferably, the dextrin is maltodextrin.

Preferably, the adding amount of the auxiliary materials accounts for 10-30% of the mass of the extract powder, specifically 10-20%, 20-30% and preferably 20%.

Preferably, the dry granulation conditions are: the horizontal conveying speed is 25-40r/min, specifically 25-30r/min, 30-40r/min, preferably 30r/min; the speed of the press roll is 3.0-5.5r/min, specifically 3.0-4.5r/min, 4.5-5.5r/min, preferably 5.0r/min.

The dry granulation is a granulation method in which the medicine powder and the auxiliary materials are uniformly mixed and directly compressed into larger tablets or tablets without using a wetting agent or a liquid adhesive, and then the tablets or the tablets are crushed again into granules with the required size.

Among the above granulation process parameters, the horizontal feed rate and the press roll speed are the main influencing factors of dry granulation. The horizontal feeding speed is a key step of dry granulation, when the speed is too high, the extract powder amount between the two rollers can be accumulated continuously, the side leakage of the extract powder is easy to occur, even the machine is blocked, the locking phenomenon occurs, and the granule yield can be reduced. The speed of the press rolls determines the residence time of the material in the nip zone between the rolls, and in a certain range, the particle formation rate increases significantly as the rotational speed of the press rolls increases, but decreases once the rotational speed of the press rolls exceeds a certain parameter value. Since dry granulation is a continuous process, it is necessary to adapt the horizontal transfer speed to the press roll speed in order to ensure good continuity and uniformity of the extract powder.

In a second aspect, the invention provides a method for forming particles in a large scale building, which method comprises the step of changing the viscosity of the particles in the large scale building.

The third aspect of the invention provides a method for preparing high-viscosity Dajianzhong granule containing maltose, which comprises the following steps: extracting fructus Zanthoxyli, zingiberis rhizoma and Ginseng radix decoction pieces with water, filtering, adding maltose into the obtained extractive solution, mixing, concentrating, granulating with the above molding method for preparing granule containing maltose, and sieving to obtain granule.

Preferably, the ratio of the added mass of the pepper to the dried ginger to the ginseng is 8.0-10.0:55.0-56.0:27.0-28.0, specifically, such as 8.5-9.5:55.1-55.5:27.2-27.8, preferably 9.0:55.2:27.6.

Preferably, the extraction is performed with an appropriate amount of water. Specifically, the water is added in an amount of 6 times, 8 times or 10 times, preferably 8 times.

The extraction is a method for decocting medicinal materials in water to obtain juice which is conventionally used.

Preferably, the number of water extractions is not less than 2, such as in particular 2-3, preferably 2.

The filtration is a conventional manner using nylon cloth or screen.

Preferably, the ratio g of the added volume ml of the maltose to the mass of the pepper is 150-250:8.0-10.0, such as 180-220:8.8-9.2, preferably 200:9.0. The mixing mode of the maltose is as follows: adding maltose into the extractive solution, and stirring for thawing.

Preferably, the concentration is reduced pressure concentration.

Preferably, the concentration is such that the relative density of the extract of the sample in the large building is 1.23-1.25 at 24-26 ℃, preferably 1.24 at 25 ℃.

Preferably, the amount of the sample extract in the large building is 95-105g, preferably 100g.

Preferably, the sieving is performed sequentially through a No. 1 sieve screen and a No. 2 sieve screen. The mesh of the screen mesh of the No. 1 screen is 9-11, preferably 10; the mesh size of the No. 2 sieve is 23-25 mesh, preferably 24 mesh.

Preferably, the particle size d of the particles in the large scale is in the range of 22 mesh < d <9 mesh, preferably 24 mesh < d <10 mesh.

The fourth aspect of the invention provides a high-viscosity granule containing maltose, which is prepared by the preparation method of the high-viscosity granule containing maltose.

As described above, the method for forming the high-viscosity middle-sized particles of the large-sized building provided by the invention breaks through the limitation of conventional operation, combines the preferred process conditions in a spray drying mode, directly carries out spray drying on the extract of the middle-sized building containing a large amount of viscous maltose without adding any auxiliary materials, and then carries out dry granulation after adding the lubricant and the auxiliary materials into the obtained extract powder so as to form the particles of the middle-sized building sample. The invention also provides an application of the method for forming the high-viscosity large-scale intermediate granule containing maltose in preparing large-scale intermediate granule. The invention further provides a preparation method of the high-viscosity Dajianzhong granule containing maltose and the Dajianzhong granule prepared by the preparation method. Has the following beneficial effects:

(1) The invention provides a method for forming high-viscosity Dajianzhong granules containing maltose, which is used for establishing a unique method and process conditions suitable for preparing the high-viscosity Dajianzhong decoction granules containing the maltose by selecting a drying mode, a granulating process, auxiliary materials, proportions and the like. Because the prescription contains a large amount of maltose, the spray drying process is short in time consumption and very rapid in drying speed, the obtained material is small in granularity and low in water content, granulation is convenient, the heating time of the medicine can be reduced, the destruction of active ingredients due to long-time high temperature is avoided, and the preparation method is suitable for continuous mass production. If the maltose is dried in vacuum, the maltose is difficult to be dried completely, the consumed time is long, the granularity of the dried material is large, the granulating is inconvenient, more energy is consumed in the actual production process, and the production is inconvenient.

(2) The invention provides a method for forming high-viscosity large-scale medium-size particles containing maltose, which creatively discovers that dry powder with good fluidity and uniform quality can be obtained without adding auxiliary materials during spray drying, the drug loading rate of the powder is improved, and the preparation method of concentrated solution is more convenient, so that the whole operation process is simpler. The research result of the invention shows that the powder yield is about 93.31% when the powder is dried without adding auxiliary materials, and the powder yield is higher than that of the powder with the auxiliary materials, and the powder wall sticking condition is lighter, so that the auxiliary materials can not be added in the drying process, the medicine carrying capacity of the extract powder is improved, and the administration dosage is reduced.

(3) The invention provides a method for forming granules in large-scale construction, which changes the high viscosity containing maltose, creatively discovers that the amount of auxiliary materials added in the dry granulation process is less, ensures the quality of granules, simultaneously further reduces the dosage of patients to the greatest extent, and improves the compliance of patients. In particular, the dry granulation has the characteristics of small auxiliary material consumption, repeated granulation, simple and convenient process, high production efficiency, low cost and the like, and particularly for granulating damp-heat sensitive materials, the contact between the materials and water and heat can be reduced to the greatest extent, and the stability of the preparation process is improved. The wet granulation method has the advantages that the amount of auxiliary materials required to be added is large, so that larger administration dosage is brought and the stability of the extract is damaged.

(4) The invention provides a method for forming high-viscosity Dajianzhong granule containing maltose, which takes the fact that the hygroscopicity of extract powder after spray drying is strong due to the fact that a large amount of maltose is contained in a prescription into consideration, and therefore dextrin is preferably added as an auxiliary material in dry granulation. The dextrin has the advantages of no peculiar smell, good solubility, difficult moisture absorption, good stability and the like, can improve the formability of the particles so as to achieve better clinical use effect, has lower price and can reduce the production cost. The dry granulation auxiliary material has less addition, reduces the dosage while guaranteeing the quality of the granules, and improves the compliance of patients.

(5) Compared with the molding process of other traditional Chinese medicine prescription granules, the molding method for changing the high-viscosity granule in large-scale construction provided by the invention has the advantages of simple process operation, less addition of auxiliary materials, high drug loading and small administration dosage, and effectively solves the preparation problem that granules cannot be prepared due to the fact that a large amount of maltose is contained in the prescription in large-scale construction, and has very strong applicability and innovation for preparing granules in large-scale construction.

Drawings

Fig. 1 shows the appearance of maltose.

Fig. 2 shows the wall sticking after spray drying in fig. 2a, 2b, 2c, 2d according to the invention. Wherein, fig. 2a is a situation diagram without adding auxiliary materials; FIG. 2b is a diagram of the addition of soluble starch; FIG. 2c is a diagram showing the addition of maltodextrin; fig. 2d is a graph showing the situation with HPMC addition.

FIG. 3 is a view showing the appearance of powder after spray drying without adding auxiliary materials in the present invention.

Fig. 4 shows the results of an examination of fig. 4a, 4b, 4c, 4d, 4e, 4f using different feed rates and nip roll speeds in the present invention. Wherein, in FIG. 4a, the feeding speed is 40r/min and the pressing roller speed is 3.0r/min; in FIG. 4b, the feed speed was 35r/min and the press roll speed was 3.0r/min; in FIG. 4c, the feed speed was 30r/min and the press roll speed was 3.0r/min; in FIG. 4d, the feed speed is 30r/min and the press roll speed is 4.0r/min; in FIG. 4e, the feed speed is 30r/min and the press roll speed is 4.5r/min; in FIG. 4f, the feed rate was 30r/min and the nip roll speed was 5.0r/min.

FIG. 5 shows a histogram of the mass of the pressed particles of different adjuvant types and proportions in the present invention.

Figure 6 shows a graph of the granules of the present invention after granulation with 0.5% magnesium stearate +20% dextrin and sieving.

Fig. 7 shows photographs 7a and 7b of the extract of comparative example 1 and example 3 after vacuum drying and spray drying. Wherein, fig. 7a is a photograph of the extract of comparative example 1 after vacuum drying; FIG. 7b is a photograph of the extract of example 3 after spray drying.

Fig. 8 shows photographs 8a, 8b of the granules of comparative example 1 using wet granulation and example 3 using dry granulation in the present invention. Wherein, fig. 8a is a photograph of the granules of comparative example 1 after wet granulation; fig. 8b is a photograph of the granules of example 3 after dry granulation.

Detailed Description

The invention is further illustrated below in connection with specific examples, which are to be understood as being illustrative of the invention and not limiting the scope of the invention.

Other advantages and effects of the present invention will become apparent to those skilled in the art from the following disclosure, which describes the embodiments of the present invention with reference to specific examples. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention.

It should be understood that the process equipment or devices not specifically identified in the examples below are all conventional in the art; all pressure values and ranges refer to relative pressures.

Furthermore, it is to be understood that the reference to one or more method steps in this disclosure does not exclude the presence of other method steps before or after the combination step or the insertion of other method steps between these explicitly mentioned steps, unless otherwise indicated; it should also be understood that the combined connection between one or more devices/means mentioned in the present invention does not exclude that other devices/means may also be present before and after the combined device/means or that other devices/means may also be interposed between these two explicitly mentioned devices/means, unless otherwise indicated. Moreover, unless otherwise indicated, the numbering of the method steps is merely a convenient tool for identifying the method steps and is not intended to limit the order of arrangement of the method steps or to limit the scope of the invention in which the invention may be practiced, as such changes or modifications in their relative relationships may be regarded as within the scope of the invention without substantial modification to the technical matter.

The reagents and instrumentation used in the following examples were as follows:

1. reagent(s)

The preparation method comprises the following steps of (1) dry ginger decoction pieces (from Shanghai Qing Pu traditional Chinese medicine decoction piece limited company, yunnan province of origin), chinese prickly ash decoction pieces (from Shanghai Qing Pu traditional Chinese medicine decoction piece limited company, sichuan province of origin), ginseng decoction pieces (from Shanghai Qing Pu traditional Chinese medicine decoction piece limited company, jilin province of origin), maltose (from Umbelliferae Torillic food limited company), magnesium stearate (from Anhui mountain river pharmaceutic adjuvant limited company), dextrin (from Jiaxing city white wave starch product limited company), soluble starch (from Anhui mountain river pharmaceutic adjuvant limited company), lactose (from DFE Pharma); extract of Dajianzhong (self-extracted from Shanghai medical Xingling scientific and technological pharmaceutical Co., ltd.); methanol (analytically pure, national drug group); methanol (chromatographic purity, shanghai Aldamus reagent Co.); acetonitrile, (chromatographic purity, shanghai Di Ke Ma technologies Co., ltd.).

The decoction pieces and maltose are used for preparing extract of Dajian, the auxiliary materials are used for preparing particles of Dajian, and the analytically pure and chromatographic pure reagents are used for measuring the content of components.

2. Instrument for measuring and controlling the intensity of light

The specific instrument conditions are shown in Table 1 below.

TABLE 1 Instrument Condition Meter

Example 1

9.0g of pepper, 55.2g of dried ginger and 27.6g of ginseng are weighed, then 8 times of water is added for 2 times of water extraction, the two water extracts are combined and filtered, 200ml of maltose is added and stirred for melting, and the mixture is decompressed and concentrated to have the relative density of 1.24 (25 ℃), thus obtaining the large-scale Chinese medicine sample extract No. 1. The appearance of added maltose is shown in figure 1, the performance parameters of the maltose are shown in table 2, and the added maltose has high viscosity.

TABLE 2 Properties and parameters of maltose

Example 2

9.2g of pepper, 55.5g of dried ginger and 27.1g of ginseng are weighed, 10 times of water is added for water extraction for 2 times, the two filtrates are combined, 205ml of maltose is added and stirred for melting, and the mixture is concentrated under reduced pressure until the relative density is 1.23 (25 ℃), thus obtaining the Dajian Zhongjia sample No. 2.

Example 3

100g of Dajianzhong sample extract No. 1 prepared in example 1 is directly subjected to spray drying without adding any auxiliary materials, and spray drying is performed under the conditions that the inlet air temperature is set to be 110 ℃, the inlet liquid speed is set to be 4.5ml/min, and the atomization pressure is set to be 1.35bar, so that extract powder No. 1 is obtained. And adding 50g of extract powder 1# into magnesium stearate, wherein the adding amount of the magnesium stearate accounts for 0.5% of the mass of the extract powder 1#. And adding dextrin, wherein the adding amount of the dextrin accounts for 20% of the mass of the extract powder 1#. Then dry granulating at a horizontal conveying speed of 30r/min and a press roller speed of 5.0r/min to form particles of the large-scale middle-size samples, and sieving sequentially through a screen with 10 meshes and a screen with 24 meshes to obtain large-scale middle-size particles 1#.

Example 4

100g of Dajian sample extract No. 1 prepared in example 1 is directly subjected to spray drying without adding any auxiliary materials, and spray drying is performed under the conditions that the air inlet temperature is set to 112 ℃, the liquid inlet speed is set to 4.7ml/min, and the atomization pressure is set to 1.05bar, so that extract powder No. 2 is obtained. And adding 50g of extract powder 1# into magnesium stearate, wherein the adding amount of the magnesium stearate accounts for 0.4% of the mass of the extract powder 1#. And adding dextrin, wherein the adding amount of the dextrin accounts for 21% of the mass of the extract powder 2#. And then carrying out dry granulation at a horizontal conveying speed of 32r/min and a compression roller speed of 4.5r/min to form particles of the large-scale middle-size building sample, and sieving the particles sequentially through a screen with 10 meshes and a screen with 24 meshes to obtain a large-scale middle-size building particle sample No. 2.

Example 5

1. Vacuum drying process investigation

The extract 1# of the Dajian sample prepared in example 1 was dried under vacuum at 60 deg.c, 70 deg.c and 80 deg.c, the vacuum degree was set to-0.9 to-1.0 bar, the time required for complete drying was recorded, and the drying time and the transfer rate of the contents of each component in the dry extract powder were used as evaluation indexes, and the results are shown in table 3.

1.1 the content of each component in the dry extract powder is determined by HPLC method, and the corresponding chromatographic conditions are as follows:

rutin, hyperin (content measurement index component in pricklyash): chromatographic column: kromasil 100-5-C18M05CLA25 (250 mm. Times.4.6 mm,5 μm); mobile phase: 0.3% formic acid (a) -acetonitrile (B); flow rate: 1.0ml/min; column temperature: 35 ℃; detection wavelength: 256nm; sample injection amount: 5 μl; elution gradient: 0-40 min,14% B; 40-41 min, 14-90% B; 41-50 min,90% B.

6-gingerol (content measurement index component in dried ginger): chromatographic column: two Kromasil 100-5-C18M05CLA25 (250 mm. Times.4.6 mm,5 μm) columns were connected in series; mobile phase and proportion: 60% water (a) -40% acetonitrile (B); flow rate: 0.7ml/min; column temperature: 30 ℃; detection wavelength: 280nm; sample injection amount: 10 μl.

Ginsenoside Rg1+Re and ginsenoside Rb1 (index component for measuring content in Ginseng radix): chromatographic column: kromasil 100-5-C18M05CLA25 (250 mm. Times.4.6 mm,5 μm); mobile phase: water (a) -acetonitrile (B); flow rate: 1.0ml/min; column temperature: 35 ℃; detection wavelength: 203nm; sample injection amount: 10 μl; elution gradient: 0-35 min,19% B; 35-60 min, 19-29% B; 60-75 min,29% B; 75-105 min, 29-40% B; 105-106 min, 40-90% B; 106-115 min,90% B.

1.2 preparation of control solution:

precisely weighing rutin and hyperoside reference substance, and adding methanol to prepare mixed standard solution containing 0.1mg of each 1 ml;

precisely weighing 6-gingerol reference substance, and adding methanol to prepare reference substance solution containing 0.1mg per 1 ml;

precisely weighing ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 reference substances, and adding methanol to prepare mixed standard solution containing 0.2mg of each 1 ml.

1.3 preparation of sample solution:

precisely weighing 1g of dry extract powder, placing into conical flask with plug, adding 2ml of water to dissolve completely, adding 3ml of methanol, weighing, performing ultrasonic treatment for 30min, weighing again, adding methanol to make up the weight, shaking, and filtering.

TABLE 3 vacuum drying time-consuming at different temperatures and transfer rates of the components (n=3)

As is clear from Table 2, the transfer rate of each component was the highest when vacuum-dried at 60℃but the time was long, and the transfer rate of each component was also close to 60℃at 70℃but the time was long, and the method was not applicable to the actual production process.

2. Spray drying process investigation

Taking a large-scale Chinese medicinal preparation 1# prepared in example 1, respectively adding three auxiliary materials including soluble starch, maltodextrin and hydroxypropyl methylcellulose (HPMC-E5) and no auxiliary materials, and spray drying in a spray dryer, wherein HPMC is added according to 2%, and the rest auxiliary materials are added according to 20% of solid matters contained in the extracting solution.

Spray drying conditions: the inlet air temperature was 150 ℃ (at which point the outlet air temperature was about 100 ℃), the inlet air velocity was 20% (i.e. 20 x 0.3=6 ml/min) and the atomisation pressure was 0.55bar. And screening the types of auxiliary materials by taking the powder yield and the wall sticking condition as evaluation indexes. The results are shown in Table 4 and FIG. 2, the powder wall built-up after spray drying is shown in FIG. 2, and the spray dried extract powder is shown in FIG. 3.

Yield (%) =weight of powder in collector/(solid content×volume of drug solution) ×100%

TABLE 4 spray drying with different adjuvants

From the results, the wall sticking condition after drying and the powder yield are shown, the wall sticking condition of the powder is slightly more serious than the rest conditions after maltodextrin is added, and the powder yield is highest and the wall sticking condition is not obvious when no auxiliary material is added.

3. Dry granulation process investigation

3.1 conditions for Dry granulation

50g of extract powder 1# prepared in example 3 (containing 0.5% magnesium stearate) was taken each time, and the dry granulator was examined for different horizontal feed rates and press roll speeds, and other granulation conditions were the same as in example 3, and the results are shown in fig. 4 and table 5.

TABLE 5 investigation of horizontal feed speed and press roll speed

From the above results, it is clear that the above different horizontal feed speeds and press roll speeds can be used for dry granulation. However, when the horizontal speed is 30r/min and the press roller speed is 5.0r/min, the powder leakage phenomenon is the lightest, the continuity of the blank sheet is better, the speeds of the powder input roller and the compressed roller are matched, and the granulating effect is the best.

3.2 screening of auxiliary Material types and proportions

Dextrin, soluble starch and lactose in different proportions are added for granulating, 100g of extract powder 1# prepared in example 3 (containing 0.5% magnesium stearate) is taken for granulating according to the conditions of example 3. The total weight of the obtained particles in the large building is weighed after twice pressing, the results are shown in table 6 and fig. 5, and the particles after sieving are shown in fig. 6.

TABLE 6 screening and investigation of the types and proportions of auxiliary materials

From the above results, it is found that the yields of dextrin and soluble starch particles decrease and the yields of lactose particles increase with increasing the proportion of the auxiliary materials, and if the proportion of the auxiliary materials is controlled to be within 20%, dextrin is selected as the optimal auxiliary material.

Example 6

3 samples of Dajianzhong granule were prepared as in example 3, and the powder yield, water content and index component content were measured, respectively, and the results are shown in Table 7.

Wherein, the powder yield is as follows: powder yield (%) = powder weight in collector/(solid content x volume of drug solution) ×100% calculation; the water content is measured by a water content measuring instrument, and the measuring method comprises the following steps: firstly peeling an empty sample tray, then placing 1-2 g of sample on the sample tray, paving, closing an upper cover, clicking for measurement, and recording the water content after the reading number is stable. The method for measuring the content of the index component was the same as in example 5.

Table 7. Results of verification test (n=3)

The results show that the granule has higher powder yield and lower water content, and the content of each index component is higher and relatively stable, so that the method has reasonable process and better stability.

Example 7

Compared with the molding process of other traditional Chinese medicine prescription granules, the method adopts less addition of auxiliary materials and high drug loading, and the specific comparison is shown in Table 8.

TABLE 8 other prescriptions granulating auxiliary materials types and proportions

Comparative example 1

Because a large amount of high viscosity maltose is an insurmountable difficulty for the drying process and the granulating method in the traditional granule preparation process. Therefore, for the molding process of the high-viscosity middle-sized particles containing maltose, the process parameters (such as concentration density, drying temperature, drying time, extract morphology, extract powder yield and water content, etc.) of different drying methods (vacuum drying and spray drying) are compared, and then the process parameters (such as auxiliary material proportion, molding or not, granulating time, granule yield and granule morphology, etc.) of different granulating methods (wet granulating and dry granulating) are compared with the middle-sized particle sample 1# prepared in example 3. The comparative data are shown in tables 9 and 10 and in figures 7 and 8.

As a comparison example, the preparation process adopts a vacuum drying and wet granulation process, the drying time is up to 29 hours, the dried extract is required to be prepared into fine powder through a crushing process, the extract is easy to absorb moisture in the crushing process, the wet granulation can be formed by using 50% of granules as auxiliary materials, the formed wet granules can be prepared into dry granule finished products through a drying step, and the granule yield is 56.7%. In example 3, the same weight of extract powder is prepared by spray drying for only 45 minutes and is in powder form after drying, the powder is not required to be crushed, the dosage of auxiliary materials for dry granulation is 20%, and the granule yield is 91.4%. Thus, the large-scale median particle sample 1# prepared in example 3 is significantly better than the particle sample prepared by the conventional vacuum drying method and wet granulation process.

TABLE 9 comparison of drying Process for comparative example 1 and example 3

Table 10. Comparison of the pelletization process of comparative example 1 and example 3

In summary, the method for forming the high-viscosity middle-jiao granule containing maltose has the advantages of simple process operation, less addition of auxiliary materials and high drug loading capacity, and effectively solves the problems that the middle-jiao granule containing maltose is large in quantity and difficult to prepare granules in a middle-jiao prescription. Therefore, the invention effectively overcomes various defects in the prior art and has high industrial utilization value.

The above embodiments are merely illustrative of the principles of the present invention and its effectiveness, and are not intended to limit the invention. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all equivalent modifications and variations of the invention be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.

Claims

1. A method for forming particles in a large building to modify the viscosity of the particles containing maltose, comprising: directly spray-drying extract of the large-scale middle-building sample containing maltose without adding any auxiliary materials, adding lubricant and auxiliary materials into the obtained extract powder, and performing dry granulation to form particles of the large-scale middle-building sample.

2. The method for forming high viscosity large scale medium particles containing maltose according to claim 1, wherein the spray drying conditions are: the temperature of the air inlet is 105-130 ℃; the liquid inlet speed is 4.0-7.5ml/min; the atomization pressure is 0.41-1.8bar.

3. The method for forming high viscosity large scale medium granule containing maltose according to claim 1, wherein the lubricant is magnesium stearate; and/or the addition of the lubricant accounts for 0.4-0.6% of the mass of the extract powder.

4. The method for forming high viscosity large and medium sized particles containing maltose according to claim 1, wherein the auxiliary material is selected from one of dextrin, soluble starch or lactose; and/or the addition of the auxiliary materials accounts for 10-30% of the mass of the extract powder.

5. The method for forming high viscosity large middle-sized granules containing maltose according to claim 1, wherein the dry granulation conditions are: the horizontal conveying speed is 25-40r/min; the speed of the press roller is 3.0-5.5r/min.

6. Use of the modified high viscosity middle of large building granule containing maltose according to any of claims 1-5 for preparing middle of large building granule.

7. A preparation method of high viscosity granule containing maltose comprises: extracting fructus Zanthoxyli, zingiberis rhizoma and Ginseng radix decoction pieces with water, filtering, adding maltose into the obtained extractive solution, mixing, concentrating, granulating with the molding method of modified maltose-containing high viscosity granule of Dajianzhong in any one of claims 1-5, and sieving to obtain Dajianzhong granule.

8. The method for preparing high viscosity granule for large scale construction containing maltose according to claim 7, wherein the large scale construction sample extract comprises any one or more of the following preparation conditions:

a1 The mass ratio of the pepper to the dried ginger to the ginseng is 8.0-10.0:55.0-56.0:27.0-28.0;

a2 A proper amount of water for the extraction;

a3 The number of times of water extraction is not less than 2;

a4 The ratio of the added volume of the maltose to the mass of the pepper is 150-250:8.0-10.0, ml/g;

a5 The concentration is reduced pressure concentration; preferably, the relative density of the concentrated extract of the large-scale middle-building sample at 24-26 ℃ is 1.23-1.25.

9. The method for preparing high viscosity granule for large scale construction containing maltose according to claim 7, wherein the granule for large scale construction comprises any one or more of the following preparation conditions:

b1 The dosage of the sample extract in the large building for molding is 95-105g;

b2 The screening is sequentially carried out through a No. 1 screen mesh and a No. 2 screen mesh; preferably, the mesh of the screen mesh of the No. 1 screen is 9-11 meshes, and the mesh of the screen mesh of the No. 2 screen is 23-25 meshes.

10. A high viscosity granule comprising maltose, prepared by the method of preparing the high viscosity granule comprising maltose according to any one of claims 7-9.