WO2021184636A1

WO2021184636A1 - Shouhui tongbian microcapsule preparation and preparation method therefor

Info

Publication number: WO2021184636A1
Application number: PCT/CN2020/105564
Authority: WO
Inventors: 张贵民; 高艳红; 刘金宇; 关永霞
Original assignee: 鲁南厚普制药有限公司
Priority date: 2020-03-20
Filing date: 2020-07-29
Publication date: 2021-09-23
Also published as: CN111375019A

Abstract

A Shouhui Tongbian microcapsule preparation is prepared from Shouhui Tongbian extract fine powder, a capsule material, an anti-sticking agent, and a plasticizer. The Shouhui Tongbian extract fine powder is prepared from fallopia multiflora, aloe vera, semen cassia, radix ginseng, fructus lycii, colla corii asini, fructus aurantii immaturus, and rhizoma atractylodis macrocephalae. The preparation method of the Shouhui Tongbian microcapsule preparation comprises the preparation of the Shouhui Tongbian extract fine powder and the preparation of microcapsules. The Shouhui Tongbian microcapsules spherical or sphere-like, have good fluidity and low hygroscopicity, and are not prone to caking. The microcapsule preparation has obvious slow-release and targeting effects; because the release is mainly concentrated in target regions of small and large intestines, the microcapsule preparation has a direct effect, high bioavailability, and good constipation treatment effect; in addition, the microcapsule preparation can mask objectionable odors, improve taste, and enhance medication compliance.

Description

Shouhui laxative microcapsule preparation and preparation method thereof

Technical field

The invention relates to a Chinese medicine microcapsule preparation and a preparation method thereof, in particular to a Shouhui laxative microcapsule preparation and a preparation method thereof, and belongs to the field of Chinese medicine preparations.

Background technique

Chinese patent CN100453105C discloses a traditional Chinese medicine composition with laxative detoxification, weight loss and lipid-lowering functions and a preparation method thereof. The product is a traditional Chinese medicine compound preparation "Shunyishu®" and "Shouhui laxative capsule" for the treatment of functional constipation.

Technical solutions

In view of the shortcomings of the existing Shouhui laxative capsules and the need for product upgrades, the present invention is a Shouhui laxative microcapsule preparation. In terms of weight percentage, the microcapsule preparation formula includes the following ingredients: A. Shouhui laxative Extract fine powder 13.5%-27.5% B. Capsule material 67%-81% C, anti-adhesive agent 0.9%-2.5% D. Plasticizer 3.6%-5.0%.

The capsule material is a kind of gum arabic, maltodextrin, modified starch, octenyl succinate starch, dry starch syrup powder, sodium caseinate, β-lactoglobulin, soy protein isolate, and xanthan gum Or several; the anti-sticking agent is one or more of glycerol monostearate, stearyl alcohol, micronized silica gel, and titanium dioxide; the plasticizer is glycerin, polyethylene glycol 6000, polyethylene glycol One or more of alcohol 400, propylene glycol, and citric acid.

Wherein, the fine powder of Shouhui laxative extract is made of the following raw materials (parts by weight): Polygonum multiflorum 60-150, aloe 100-200, cassia 80-180, ginseng 20-80, wolfberry 30-100, donkey-hide gelatin 30 -100, Fructus Aurantii 80-150, Atractylodes 20-80; one of the preferred ones, the fine powder of Shouhui laxative extract is made of the following raw materials (parts by weight): Polygonum multiflorum 120, Aloe 160, Cassia 140, Ginseng 50, Lycium barbarum 75, donkey-hide gelatin 75, Zhishi 120, Baizhu 50.

Preferably, in terms of weight percentage, the formulation contains the following ingredients: A, Shouhui laxative extract fine powder 17.5%-23.5% B, capsule material 71.5%-77.5% C. Anti-sticking agent 1.1%-1.9% D. Plasticizer 3.8%-4.7%; preferably, in terms of weight percentage, the preparation formula contains the following ingredients: A, Shouhui laxative extract fine powder 19.7%-22.5% B, capsule material 72.3%-74.1% C , Anti-sticking agent 1.3%-1.8% D, plasticizer 3.9%-4.4%;

The capsule material is sodium complex protein by weight: starch syrup dry powder=3:2, maltodextrin: β-lactoglobulin=3:2, maltodextrin: soy protein isolate: modified starch: gum arabic=5 :3:2:1 or octenyl succinate starch: β-lactoglobulin=3:2; the anti-sticking agent is stearyl alcohol by weight: titanium dioxide=2:1 or single Glyceryl stearate; the plasticizer is polyethylene glycol 6000 by weight: citric acid=2-6:1 or propylene glycol.

Another object of the present invention is to provide a preparation method of the first hydrangea laxative microcapsule preparation, which mainly includes the preparation of the fine powder of the first hydrangea laxative extract, the preparation of the emulsion and the spray drying.

A preparation method of Shouhui laxative microcapsule preparation includes the following steps:

1) Extraction and purification process: A. Weigh the donkey-hide gelatin according to the formula, pulverize it into ultra-fine powder, sieving, and set aside;

B. Ginseng, Polygonum multiflorum, Cassia Seeds and Aloe are refluxed and extracted twice with 50%-70% ethanol, the first time is 10 times the amount, the second time is 8 times the amount, each 2 hours, respectively, filtered, and the filtrate was combined;

C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the ethanol concentration reach 50%-70% (at 25°C), keep it in the refrigerator for 24-48 hours, Filter

D. The alcohol extract of step B is combined with the decoction of step C, concentrated into a thick paste with a relative density of 1.30 to 1.35 (at 70°C), dried, crushed into fine powder, sieved, and set aside;

E. Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use;

2) Preparation process: F. Weigh the laxative extract powder, capsule material, anti-sticking agent and plasticizer of step E according to the formula quantity, and add the capsule material, anti-sticking agent and plasticizer to purified water, 45 Heat and stir at ℃-58℃ to dissolve, prepare a 22%-42% mass fraction of capsule material solution, cool to room temperature, add Shouhui laxative extract powder and emulsifier under stirring, homogenize emulsification, Obtain the emulsion for use;

G. Step F The emulsion is spray-dried under the conditions of inlet air temperature of 165°C-175°C, spray pressure of 0.36MPa-0.42MPa, and feed rate of 15ml/min-25ml/min, collect the microcapsules, and cool to obtain.

Preferably, step 1) the extraction and purification process includes the following steps: A. Weigh the donkey-hide gelatin according to the formula, pulverize it into ultra-fine powder, pass through a 150-200 mesh sieve, and set aside;

B. Ginseng, Polygonum multiflorum, Cassia seeds and Aloe are refluxed with 60% ethanol for two extractions, 10 times the amount for the first time, and 8 times the amount for the second time, for 2 hours each time, filter separately, and combine the filtrate;

C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;

D. Combine the alcohol extract of step B with the decoction of step C, concentrate into a thick paste with a relative density of 1.30 to 1.35 (70°C), dry with belt vacuum, pulverize into fine powder, sieved, and set aside;

E. Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use.

Preferably, the parameter conditions of the belt vacuum drying in step D of the 1) extraction and purification process are the vacuum degree -0.08Mpa-0.10Mpa, and the drying temperature is 50°C-60°C.

Preferably, the step 2) preparation process includes the following steps: F, weighing step E according to the formula amount, the fine powder of the first hydrangea laxative extract, the capsule material, the anti-adhesive agent and the plasticizer, the capsule material, the anti-adhesive agent Add purified water and plasticizer into purified water, heat and stir at 52°C to dissolve, prepare a 36% mass fraction of capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract and emulsifier under stirring, evenly Quality emulsification to obtain emulsion for use;

G. Step F The emulsion is spray-dried under the conditions of an inlet air temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min, collects the microcapsules, and cools them to obtain.

Preferably, the emulsifier in step 2) F is one or more of Tween 80, soybean phospholipid, lecithin, poloxamer, and sucrose fatty acid ester, and the amount is 0.4 of the total preparation formula by mass fraction. %-1.2%;

Preferably, the emulsifier in step F is a composite emulsifier of soybean phospholipid: sucrose fatty acid ester=4:6 in terms of weight ratio, and the amount is 0.9% of the total preparation formula in terms of mass fraction.

Further, the preparation method of the first hydrangea laxative microcapsule preparation of the present invention includes the following steps:

1) Extraction and purification process: A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, and pass it through a 150-200 mesh sieve for use;

C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.15 (at 80°C), place it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;

D. Combine the alcohol extract of step B with the decoction of step C, concentrate into a thick paste with a relative density of 1.30 to 1.35 (70°C), vacuum-dry it with -0.09pa, pulverize into fine powder, sieving, and set aside;

2) Preparation process: F, step E, take the fine powder, capsule material, anti-sticking agent and plasticizer of the first hydrangea laxative extract, add the capsule material, anti-sticking agent and plasticizer to purified water, and heat at 52℃ Stir to dissolve, configure it into a 36% mass fraction of the capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract and soybean phospholipid: sucrose fatty acid ester = 4:6 composite emulsifier under stirring. The dosage is 0.9% of the total amount of the formulation in terms of mass fraction. , Homogeneous emulsification to obtain the emulsion for use;

In addition to being used as ordinary powders or granules, the microcapsules of the present invention can be further used as intermediates to be filled into capsules and compressed into tablets, etc., thereby obtaining Shouhui laxative microcapsule capsules and Shouhui laxative microcapsule tablets.

Beneficial effect

1) Shouhui laxative microcapsule preparation is a drug storage type microcapsule, which is spherical or quasi-spherical, with good fluidity, low moisture absorption, good stability, and not easy to agglomerate. It can improve the easy moisture absorption of the finished product of Shouhui laxative capsule. Instability and other issues;

2) Shouhui laxative is a drug for the treatment of constipation, and its effective site is concentrated in the small intestine and large intestine. The Shouhui laxative microcapsule preparation of the present invention has obvious slow-release and targeting effects, and the drugs are mainly concentrated in the small intestine and large intestine. Regional release, which directly acts on the site of effect, has high bioavailability, and is not affected by gastrointestinal rhythms, which can exert the best effect in treating constipation;

3) The fine powder of Shouhui laxative extract can conceal the inherent bad smell and taste of Shouhui laxative preparations by embedding and concealing the capsule material, and the patients have good medication compliance.

The shouhui laxative microcapsule preparation of the invention is white or off-white powder, in a loose shape, no bad smell, good fluidity, and good dispersibility and stability. Except for individual dents on the surface of the microcapsule particles, the particles are relatively round and close to spherical, and the surface is dense and non-porous, basically without adhesion, the particle size distribution of the capsules is relatively uniform, and the particle size distribution is relatively narrow, most of which are concentrated near 20μm, and Approximately normal distribution. The measurement result of the encapsulation rate shows that the encapsulation rate of the Shouhui laxative microcapsule preparation obtained by the preparation formula and preparation process of the present invention is above 80%, up to 93.8%, and the microencapsulation effect is good.

In vitro cumulative dissolution test shows that the cumulative dissolution percentage of Shouhui laxative microcapsule capsules and Shouhui laxative microcapsule tablets of the present invention is less than 55% within 1 hour, reaches more than 80% dissolution within 2 hours, and is basically completely released within 3 hours. Compared with traditional capsules, the Shouhui laxative microcapsule preparation of the present invention has a certain slow-release effect.

The results of the accelerated stability test showed that after 6 months of storage under accelerated test conditions (40±2℃, RH 75%±5), the properties of Shouhui laxative microcapsule tablets and microcapsule capsules did not change, and the content did not change significantly. , Dissolution time limit and various inspection indicators of hygiene meet the requirements. It can be known from the above experimental data that the Shouhui laxative microcapsule preparation prepared by the present invention has good stability and controllable quality.

Description of the drawings

Figure 1 is the particle size distribution diagram of Shouhui laxative microcapsules in Example 5; Figure 2 is the particle size distribution diagram of Shouhui laxative microcapsules in Example 11; Figure 3 is the Shouhui laxative microcapsules and Shouhui laxative microcapsules The cumulative dissolution percentage curve of tablets and Shouhui laxative capsules.

Embodiments of the present invention

The present invention is further described by specific embodiments below, but the present invention is not limited to the following embodiments, and any form of equivalent replacement is obvious to a person of ordinary skill in the art and is included in the present invention.

实施例Example 1 1 首荟通便微囊胶囊Shouhui laxative microcapsules

1) Extraction and purification process: Polygonum multiflorum 120g, aloe vera 160g, cassia 150g, ginseng 20g, wolfberry 50g, donkey-hide gelatin 40g, Citrus aurantium 120g, Atractylodes macrocephala 30g, the above 8 flavors, take donkey-hide gelatin, crush into superfine powder, pass through a 180 mesh sieve , Spare; ginseng, multiflora multiflora, cassia, aloe plus 60% ethanol reflux extraction twice, the first time increase 10 times the amount, the second time increase 8 times the amount, each 2 hours, respectively, filter and combine the filtrate; Chinese wolfberry , Fructus Aurantii, Atractylodes macrocephala, decocted twice with water, the first time increased 8 times, soaked for 1 hour, decocted for 1.5 hours, the second time increased 6 times, decocted for 1.5 hours, filtered, combined the filtrate, concentrated to relative A clear paste with a density of 1.10 (at 80°C), put it to room temperature, stir and add ethanol to make the concentration reach 70% (at 25°C), keep it in the refrigerator for 36 hours, and filter; combine the above alcohol extract and decoction, and concentrate A thick paste with a relative density of 1.35 (70°C), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature 50°C, crushed into fine powder, sieved, and mixed with the above superfine powder of donkey-hide gelatin. Get 243g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract fine powder: 135g B. Gum Arabic: 540g Maltodextrin: 270g C. Glyceryl monostearate: 10g Titanium dioxide: 5g D. Polyethylene glycol 400: 40g

Add acacia gum, maltodextrin, glyceryl monostearate, titanium dioxide, polyethylene glycol 400 in the above formula into purified water, heat and stir at 50 ℃ to dissolve, and prepare a capsule material solution with a mass fraction of 40% , Cool to room temperature, add the above formula amount of laxative extract powder and 6g of poloxamer under stirring, homogenize and emulsify to obtain an emulsified liquid. At the inlet temperature of 170℃, the spray pressure of 0.38MPa, the feed Spray drying was performed at a speed of 17.5 ml/min, and the microcapsules were collected and cooled to obtain 826 g of microcapsules.

Take step 2) microcapsules, add 174g starch, fill, polish in a grinder, remove damaged capsules, and get ready.

实施例Example 2 2 首荟通便微囊片Shouhui laxative microcapsule tablets

1) Extraction and purification process: Polygonum multiflorum 80g aloe 120g cassia 100g ginseng 50g wolfberry 80g donkey-hide gelatin 80g Fructus Aurantii 80g Atractylodes 50g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 180-mesh sieve, and set aside; ginseng, fleeceflower root, cassia seed, aloe plus 70% ethanol reflux extraction for the second time, the first time increase 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.11 (at 80℃), put it to room temperature, stir and add ethanol to make the concentration reach 70% (25℃) Time), refrigerate and stand for 24 hours, and then filter; combine the above alcohol extract and decoction to concentrate into a thick paste with a relative density of 1.30 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 60 ℃, pulverized into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 256g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract fine powder: 175g B. Octenyl succinate starch: 775g

C. Micro-powder silica gel: 13g D. Propylene glycol: 37g, add the octenyl succinate starch, micro-powder silica gel, and propylene glycol in the above formula into purified water, heat and stir at 48°C to dissolve, and prepare a mass fraction of 28% The capsule material solution, cool to room temperature, add the above formula amount of Shouhui laxative extract powder and Tween-80 under stirring 12g, homogeneously emulsified to obtain an emulsion, spray-dried under the conditions of an inlet air temperature of 166°C, a spray pressure of 0.40MPa, and a feed rate of 16ml/min, collect the microcapsules, and cool to obtain 784g of microcapsules.

Take step 2) microcapsules, add 201g of sucrose powder, mix well, make coarse granules, dry, pulverize, sieving, granulate, dry at low temperature, whole granules, add 7g magnesium stearate and 8g talcum powder, mix well , Press the tablet and get it.

实施例Example 3 3 首荟通便微囊胶囊Shouhui laxative microcapsules

1) Extraction and purification process: Polygonum multiflorum 150g, Aloe 200g Cassia Seed 180g Ginseng 20g Wolfberry 30g Ejiao 30g Fructus aurantii 150g 20g Atractylodes macrocephala, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass a 200-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed, aloe plus 50% ethanol are refluxed for the second time, and the first time is 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.17 (at 80 ℃), put it to room temperature, stir and add ethanol to make the concentration reach 50% (25 ℃) Time), refrigerate and stand for 36 hours, and filter; combine the above alcohol extract and water decoction, concentrate into a thick paste with a relative density of 1.32 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 55 ℃, crushed into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 331g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract fine powder: 217g B. Dry starch syrup powder: 572g β-lactoglobulin: 143g C. Stearyl alcohol: 21g D. Glycerin: 28g Citric acid: 19g, add the starch syrup powder, β-lactoglobulin, stearyl alcohol, glycerin, and citric acid of the above formula to purified water, heat and stir at 46℃ Dissolve it and prepare it into a capsule material solution with a mass fraction of 37%, cool it to room temperature, add the above formula amount of the laxative extract powder of the above formula and 10g of sucrose fatty acid ester under stirring, and homogenize and emulsify to obtain an emulsion. Spray drying was performed under the conditions of an inlet air temperature of 168°C, a spray pressure of 0.42 MPa, and a feed rate of 15 ml/min. The microcapsules were collected and cooled to obtain 796 g of microcapsules. Take step 2) microcapsules, add 204g of micro-powder silica gel, fill, polish in a grinder, and remove damaged capsules.

实施例Example 4 4 首荟通便微囊片Shouhui laxative microcapsule tablets

1) Extraction and purification process: Polygonum multiflorum 60g, aloe 100g Cassia seed 80g ginseng 80g wolfberry 100g donkey-hide gelatin 100g citrus fruit 120g Atractylodes macrocephala 80g, the above 8 flavors, take donkey-hide gelatin, crush it into ultra-fine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed, aloe plus 70% ethanol reflux extraction 2 Add 10 times the amount for the first time, add 8 times the amount for the second time, filter separately and combine the filtrate for 2 hours each time; decoct wolfberry, citrus fruit, and Atractylodes macrocephala twice with water, add 8 times the amount for the first time , Soak for 1 hour, decoct for 1.5 hours, add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.15 (at 80 ℃), put it to room temperature, stir and add Ethanol makes the concentration reach 60% (at 25℃), keep it in the refrigerator for 48 hours, and filter; combine the above alcohol extract and water decoction, concentrate to a thick paste with a relative density of 1.34 (70℃), belt vacuum drying, Vacuum degree -0.08MPa-0.10Mpa, drying temperature 60℃, crushed into fine powder, sieved, and mixed with the above-mentioned donkey-hide gelatin superfine powder to obtain 311g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract powder: 275g B. Soy protein isolate: 372g Maltodextrin: 224g Xanthan gum: 74g C, micronized silica gel: 9g D, polyethylene glycol 6000: 46g, add the above formula amount of soy protein isolate, maltodextrin, xanthan gum, micronized silica gel, and polyethylene glycol 6000 to purified water, Heat and stir at 51℃ to dissolve, prepare a 27% mass fraction of the capsule material solution, cool to room temperature, add the above formula amount of the laxative extract powder of the above formula and 5g of lecithin, homogenize and emulsify, The obtained emulsion was spray-dried at an inlet temperature of 174°C, a spray pressure of 0.39 MPa, and a feed rate of 20 ml/min. The microcapsules were collected and cooled to obtain 806 g of microcapsules. Take step 2) microcapsules, add 178g of dextrin, mix well to make coarse particles, dry, pulverize, sieving, granulate, dry at low temperature, whole, add 8g magnesium stearate and 8g talcum powder, mix well , Press the tablet and get it.

实施例Example 5 5 首荟通便微囊胶囊Shouhui laxative microcapsules

1) Extraction and purification process (10 times the prescription amount): Polygonum multiflorum 1200g, aloe 1600g, cassia 1400g, ginseng 500g, medlar 750g, donkey-hide gelatin 750g Fructus Aurantii 1200g Atractylodes 500g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 200-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 60% ethanol reflux extraction twice, the first time increase 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.15 (at 80 ℃), put it to room temperature, stir and add ethanol to make the concentration reach 60% (25 ℃) Time), refrigerate and stand for 48 hours, and filter; combine the above alcohol extract and water decoction, concentrate into a thick paste with a relative density of 1.32 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 60 ℃, pulverized into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 2650g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract powder: 225g B. Sodium caseinate: 445g Dry starch syrup powder: 296g C, glyceryl monostearate: 13g D. Polyethylene glycol 6000: 30g Citric acid: 9g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000, citric acid into purified water, 52℃ Under the conditions, heat and stir to dissolve, prepare a 36% mass fraction of capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester under stirring, and homogenize Emulsify to obtain an emulsion, which is spray-dried at an inlet temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min. The microcapsules are collected and cooled to obtain 867 g of microcapsules. Take step 2) microcapsules, add 133g of micro-powder silica gel, fill, polish in a grinder, and get rid of damaged capsules.

实施例Example 6 6 首荟通便微囊片Shouhui laxative microcapsule tablets

1) Extraction and purification process: Polygonum multiflorum 130g, Aloe 180g, Cassia seed 150g, Ginseng 70g Wolfberry 60g Ejiao 70g Citrus aurantium 120g Atractylodes macrocephala 60g, the above 8 flavors, take donkey-hide gelatin, crush it into superfine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed, aloe plus 70% ethanol reflux extraction twice, the first time 10 times the amount, the second Add 8 times the amount each time, 2 hours each time, filter separately, and combine the filtrate; add water to decoct wolfberry, Citrus aurantium, and Atractylodes macrocephala twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours, and second Add 6 times the amount each time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.19 (at 80°C), put it to room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), Refrigerate and stand for 24 hours, then filter; combine the above alcohol extract and water decoction, concentrate into thick paste with relative density of 1.33 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature Crushed into fine powder at 55°C, sieved, and mixed with the above-mentioned superfine donkey-hide gelatin powder to obtain 325g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract powder: 260g B. Arabic gum: 510g soy protein isolate: 170g C, stearyl alcohol: 8g Micro-powder silica gel: 4g D, polyethylene glycol 6000: 48g, add the above formula amount of gum arabic, soy protein isolate, stearyl alcohol, micro-powder silica gel, polyethylene glycol 6000 into purified water, heat and stir at 58℃ to dissolve , Formulated into a capsule material solution with a mass fraction of 42%, cooled to room temperature, added the above formula amount of laxative extract powder of the above formula and 7g of sucrose fatty acid ester under stirring, and homogenized emulsification to obtain an emulsified liquid. Spray drying was performed under the conditions of a wind temperature of 166°C, a spray pressure of 0.36 MPa, and a feed rate of 20.5 ml/min. The microcapsules were collected and cooled to obtain 798 g of microcapsules. Take step 2) microcapsules, add 180g of microcrystalline cellulose, mix well, make coarse particles, dry, pulverize, sieving, granulate, dry at low temperature, sizing, add 10g magnesium stearate and 12g talc, Mix well, press tablets, and get ready.

实施例Example 7 7 首荟通便微囊Shouhui laxative microcapsules

1) Extraction and purification process: Polygonum multiflorum 75g Aloe 150g Cassia seed 90g Ginseng 50g Wolfberry 70g Ejiao 80g Citrus aurantium 120g Atractylodes macrocephala 60g, the above 8 flavors, take donkey-hide gelatin, crush it into superfine powder, pass through a 200-mesh sieve, and set aside; ginseng, fleece-flower root, cassia seed and aloe are refluxed with 50% ethanol for two times, the first time is 10 times the amount, the second time Add 8 times the amount each time, 2 hours each time, filter separately, and combine the filtrate; add water to decoct wolfberry, Citrus aurantium, and Atractylodes macrocephala twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours, and second Add 6 times the amount each time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.17 (at 80°C), put it to room temperature, stir and add ethanol to make the concentration reach 50% (at 25°C), Refrigerate and stand for 36 hours, then filter; combine the above alcohol extract and water decoction, concentrate into thick paste with relative density of 1.30 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature At 60°C, pulverize into fine powder, sieving, and mix with the above-mentioned superfine Ejiao powder to obtain 289g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract powder: 150g B. Octenyl succinate starch: 468g β-lactoglobulin: 312g C. Glyceryl monostearate: 20g D. Propylene glycol: 50g, add the octenyl succinate starch, β-lactoglobulin, glyceryl monostearate, and propylene glycol in the above formula into purified water, heat and stir at 49℃ to dissolve, and prepare the quality The capsule material solution with a fraction of 29%, cool to room temperature, add the above formula amount of Shouhui laxative extract powder and Tween-80 8g under stirring, homogenize and emulsify to obtain an emulsion, at the inlet temperature of 165℃ , Spray drying under the conditions of spray pressure 0.41MPa and feed rate 24ml/min, collect the microcapsules, and cool to obtain 806g microcapsules.

实施例Example 8 8 首荟通便微囊胶囊Shouhui laxative microcapsules

1) Extraction and purification process: Polygonum multiflorum 100g, Aloe 130g, Cassia seed 120g Ginseng 40g wolfberry 70g Ejiao 60g Citrus aurantium 100g Atractylodes 40g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 60% ethanol reflux extraction twice, Add 10 times the amount for the first time, add 8 times the amount for the second time, filter separately and combine the filtrate for 2 hours each time; decoct medlar, citrus fruit, and atractylodes macrocephala twice with water, add 8 times the amount for the first time, soak 1 hour, decocting for 1.5 hours, adding 6 times the amount for the second time, decocting for 1.5 hours, filtering, combining the filtrate, and concentrating to a clear paste with a relative density of 1.19 (at 80°C), placing it at room temperature, stirring and adding ethanol to make Concentration reaches 70% (at 25°C), keep it in the refrigerator for 48 hours, and filter; combine the above alcohol extract and water decoction to concentrate into a thick paste with a relative density of 1.32 (70°C), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature 60℃, crushed into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 281g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract powder: 190g B, maltodextrin: 474g soy protein isolate: 273g C, stearyl alcohol: 25g D. Propylene glycol: 41g, add the above formula amount of maltodextrin, soy protein isolate, stearyl alcohol, and propylene glycol to purified water, heat and stir at 45°C to dissolve, prepare a 22% mass fraction of capsule material solution, and cool To room temperature, add the above formula amount of laxative extract powder and 4g of poloxamer under stirring, homogenize and emulsify to obtain an emulsion. At the inlet temperature of 174℃, the spray pressure of 0.42MPa, and the feed rate of 25ml Under the condition of spray drying, the microcapsules were collected and cooled to obtain 839 g of microcapsules. Take step 2) microcapsules, add 161g of micro-powder silica gel, fill, polish in a grinder, and get rid of damaged capsules.

实施例Example 9 9 首荟通便微囊片Shouhui laxative microcapsule tablets

1) Extraction and purification process: Polygonum multiflorum 70g, Aloe 110g, Cassia 90g Ginseng 60g wolfberry 80g donkey-hide gelatin 80g Citrus aurantium 100g and Atractylodes 30g, the above 8 flavors, take donkey-hide gelatin, pulverize into superfine powder, pass through a 150-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 50% ethanol reflux extraction twice, the first time increase 10 times the amount , Add 8 times the amount for the second time, 2 hours each time, filter separately and combine the filtrate; add water to decoct wolfberry, citrus fruit and atractylodes macrocephalae twice, add 8 times the amount for the first time, soak for 1 hour, decoct for 1.5 hours , Add 6 times the amount for the second time, decoct for 1.5 hours, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.12 (at 80℃), put it to room temperature, stir and add ethanol to make the concentration reach 50% (25℃) Time), refrigerate and stand for 48 hours, and filter; combine the above alcohol extract and water decoction, concentrate into a thick paste with a relative density of 1.31 (70℃), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa , The drying temperature is 50 ℃, pulverized into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 263g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract powder: 183g B. Gum Arabic: 756g C. Glyceryl monostearate: 10g Titanium dioxide: 6g D. Citric acid: 45g, add acacia, glyceryl monostearate, titanium dioxide, and citric acid in the above formula into purified water, heat and stir at 50℃ to dissolve, and prepare a 32% mass fraction of capsule material solution , Cool to room temperature, add the above formula amount of laxative extract powder and 5g of lecithin under stirring, homogenize and emulsify to obtain an emulsified liquid, at the inlet temperature of 175℃, the spray pressure of 0.38MPa, and the feed rate of 18.5 Spray drying is performed under the condition of ml/min, and the microcapsules are collected and cooled to obtain 811 g of microcapsules. Take step 2) microcapsules, add 173g starch, mix well, make coarse granules, dry, pulverize, sieving, granulate, dry at low temperature, whole granules, add 5g magnesium stearate and 11g talcum powder, mix well, Press the tablet and get it.

实施例Example 10 10 首荟通便微囊胶囊Shouhui laxative microcapsules

1) Extraction and purification process: Polygonum multiflorum 90g, Aloe 130g, Cassia seed 120g Ginseng 40g wolfberry fruit 70g donkey-hide gelatin 50g citrus fruit 90g atractylodes 40g, the above 8 flavors, take donkey-hide gelatin, crush into superfine powder, pass through a 180-mesh sieve, and set aside; ginseng, fleece-flower root, cassia, aloe plus 60% ethanol reflux extraction twice, Add 10 times the amount for the first time, add 8 times the amount for the second time, filter separately and combine the filtrate for 2 hours each time; decoct medlar, citrus fruit, and atractylodes macrocephala twice with water, add 8 times the amount for the first time, soak 1 hour, decocting for 1.5 hours, adding 6 times the amount for the second time, decocting for 1.5 hours, filtering, combining the filtrate, and concentrating to a clear paste with a relative density of 1.16 (at 80°C), placing it at room temperature, stirring and adding ethanol to make Concentration reaches 70% (at 25°C), keep it in refrigeration for 36 hours, and filter; combine the above alcohol extract and water decoction to concentrate into a thick paste with a relative density of 1.34 (70°C), belt vacuum drying, vacuum degree -0.08MPa--0.10Mpa, drying temperature 50℃, crushed into fine powder, sieved, and mixed with the above-mentioned superfine powder of donkey-hide gelatin to obtain 303g of fine powder of Shouhui laxative extract.

2) Preparation process: A. Shouhui laxative extract powder: 176g B. Maltodextrin: 349g Soy protein isolate: 210g Modified starch: 140g Gum arabic: 70g C, Glyceryl monostearate: 16g D. Glycerin: 39g, add the above formula amount of maltodextrin, soy protein isolate, modified starch, acacia, glycerol monostearate, and glycerin to purified water, heat and stir at 47°C to dissolve, and prepare the mass fraction It is a 39% capsule material solution, cooled to room temperature, and under stirring, add the above formula amount of Shouhui laxative extract powder and Tween-80 11g, homogenize and emulsify to obtain an emulsion. At the inlet temperature of 169℃, Spray drying was performed under the conditions of a spray pressure of 0.41 MPa and a feed rate of 21 ml/min. The microcapsules were collected and cooled to obtain 837 g of microcapsules.

Take step 2) microcapsules, add 163g lactose, fill, polish in a grinder, remove damaged capsules, and get ready.

实施例Example 11 11 首荟通便微囊片Shouhui laxative microcapsule tablets

The fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5.

Preparation process: A, Shouhui laxative extract powder: 197g B, sodium caseinate: 445g Starch syrup dry powder: 296g C. Stearyl alcohol: 12g Titanium dioxide: 6g D. Propylene glycol: 44g, add sodium caseinate, dry starch syrup powder, stearyl alcohol, titanium dioxide, propylene glycol in the above formula into purified water, heat and stir at 52℃ to dissolve, and prepare a capsule material with a mass fraction of 36% The solution was cooled to room temperature, and the above formula was added with the above formula amount of laxative extract powder, 3.6g of soy phospholipid and 5.4g of sucrose fatty acid ester, homogenized and emulsified to obtain an emulsified liquid. At the inlet temperature of 172℃, Spray drying was performed under the conditions of spray pressure of 0.39MPa and feed rate of 22.5ml/min, and the microcapsules were collected and cooled to obtain 852g of microcapsules. Take step 2) microcapsules, add 131g of dextrin, mix well, make coarse particles, dry, pulverize, sieving, make granules, dry at low temperature, and sizing, add 8g magnesium stearate and 9g talcum powder, and mix well , Press the tablet and get it.

对比实施例Comparative example 1 1 首荟通便微囊Shouhui laxative microcapsules

Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C. Glyceryl monostearate: 13g D. Polyethylene glycol 6000: 39g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, and polyethylene glycol 6000 to purified water ，Heat and stir at 52℃ to dissolve, prepare a 36% mass fraction of capsule material solution, cool to room temperature, add Shouhui laxative extract powder, 3.6g soy phospholipid, and 5.4g sucrose fatty acid ester under stirring. , Homogeneous emulsification to obtain an emulsion, spray drying at an inlet temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min. The microcapsules are collected and cooled to obtain 785 g of microcapsules.

对比实施例Comparative example 2 2 首荟通便微囊Shouhui laxative microcapsules

Preparation process: A, Shouhui laxative extract powder: 225g B, maltodextrin: 506g β-lactoglobulin: 217g C, glycerol monostearate: 13g D. Citric acid: 39g, add the above formula amount of maltodextrin, β-lactoglobulin, glycerol monostearate, polyethylene glycol 6000 to purified water, heat and stir at 52℃ to dissolve, and prepare the quality 36% of the capsule material solution, cool to room temperature, add Shouhui laxative extract powder, 3.6g of soy phospholipids, and 5.4g of sucrose fatty acid ester under stirring, homogenize and emulsify to obtain an emulsion, at the inlet temperature Spray drying was performed under the conditions of 172°C, spray pressure 0.39 MPa, and feed rate 22.5 ml/min. The microcapsules were collected and cooled to obtain 794 g of microcapsules.

对比实施例Comparative example 3 3 首荟通便微囊Shouhui laxative microcapsules

Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C, glycerol monostearate: 13g D, polyethylene glycol 6000: 26g Citric acid: 13g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 to purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction as 36% of the capsule material solution, cool to room temperature, add Shouhui laxative extract powder, 3.6g soy phospholipid, 5.4g sucrose fatty acid ester under stirring, homogenize and emulsify to obtain an emulsified liquid, at the inlet temperature of 172℃ , Spray drying under the conditions of spray pressure 0.39MPa and feed rate 22.5ml/min, collect microcapsules and cool to obtain 791g microcapsules.

对比实施例Comparative example 4 4 首荟通便微囊Shouhui laxative microcapsules

Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C, glycerol monostearate: 13g D. Polyethylene glycol 6000: 31.2g Citric acid: 7.8g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 to purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction It is a 36% capsule material solution, cooled to room temperature, and while stirring, add the fine powder of Shouhui laxative extract, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester, and homogenize and emulsify to obtain an emulsion. At the inlet temperature of 172 Under the conditions of ℃, spray pressure of 0.39MPa, and feed rate of 22.5ml/min, spray drying was performed, and the microcapsules were collected and cooled to obtain 823g of microcapsules.

对比实施例Comparative example 5 5 首荟通便微囊Shouhui laxative microcapsules

Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C. Glyceryl monostearate: 13g D. Polyethylene glycol 6000: 32.5g Citric acid: 6.5g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 into purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction It is a 36% capsule material solution, cooled to room temperature, and under stirring, add Shouhui laxative extract powder, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester, homogenize and emulsify to obtain an emulsified liquid, at an inlet temperature of 172 Under the conditions of ℃, spray pressure of 0.39MPa, and feed rate of 22.5ml/min, spray drying was performed, and the microcapsules were collected and cooled to obtain 817g of microcapsules.

对比实施例Comparative example 6 6 首荟通便微囊Shouhui laxative microcapsules

Preparation process: A. Shouhui laxative extract fine powder: 225g B. Maltodextrin: 506g β-lactoglobulin: 217g C. Glyceryl monostearate: 13g D. Polyethylene glycol 6000: 33.4g Citric acid: 5.6g, add the above formula amount of maltodextrin, β-lactoglobulin, glyceryl monostearate, polyethylene glycol 6000 into purified water, heat and stir at 52℃ to dissolve, and prepare the mass fraction It is a 36% capsule material solution, cooled to room temperature, and while stirring, add the fine powder of Shouhui laxative extract, 3.6g of soybean phospholipid, and 5.4g of sucrose fatty acid ester, and homogenize and emulsify to obtain an emulsion. At the inlet temperature of 172 Under the conditions of ℃, spray pressure 0.39MPa, and feed rate of 22.5ml/min, spray drying was performed, and the microcapsules were collected and cooled to obtain 805 g of microcapsules.

对比实施例Comparative example 7 7 首荟通便颗微囊的制备Preparation of Shouhui laxative microcapsules

The fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5. The microcapsule preparation method used refers to the best effect example 5 of the Chinese patent "A compound vinegar microcapsule and its preparation method and application (authorization announcement number CN106036829B)" to investigate the application of the prior art microcapsule preparation method to Shouhui The preparation effect achieved when the laxative extract is fine powder.

Preparation process: A. Shouhui laxative extract fine powder: 222g B. 3% sodium alginate solution: 778g, add the fine powder of the first hydrangea laxative extract of the above formula to the 3% sodium alginate solution to prepare the microcapsule core mixture, in which the sodium alginate The weight ratio of the fine powder of Shouhui laxative extract is 3.5:1; mix the above-mentioned capsule core mixture uniformly, and drip into the 1.5% chitosan and 3.5% calcium chloride mixture system under stirring. Microencapsulation and embedding;

The microcapsules prepared above are sent to a spray dryer for spray drying with a pump, and the air inlet temperature is controlled to be 185°C and the spray pressure is 0.185MPa. Finally, the microcapsules are drained to obtain 245g of finished microcapsules.

对比实施例Comparative example 8 8 首荟通便微囊的制备Preparation of Shouhui laxative microcapsules

The fine powder of Shouhui laxative extract used in this example is the fine powder of Shouhui laxative extract obtained in step 1) of the extraction and purification process in Example 5. The microcapsule preparation method used refers to "Hu Rui, Zhou Guangping, Song Weichun. Preparation and in vitro controlled release analysis of Chinese medicine prebiotic microcapsules by spray drying method[J]. Anhui Agricultural Sciences, 2016, 44(29): 89-94." The best microcapsule preparation process is that the capsule material is gelatin: sodium alginate=1:3, the mass fraction of the core material is 20%, the air inlet temperature is 187℃, the air outlet temperature is 60℃, and the feed rate is 32mL/min.

Preparation process: A. Shouhui laxative extract fine powder: 200g B. Gelatin: 200g Sodium alginate: 600g, add the gelatin and sodium alginate of the above formula into purified water, heat and stir at 50℃ to dissolve, prepare a capsule material solution with a mass fraction of 4%, cool to room temperature, add the first under stirring The fine powder of Hui laxative extract was homogenized and emulsified to obtain an emulsion, which was spray-dried under the conditions of air inlet temperature of 187°C, air outlet temperature of 60°C, spray pressure of 0.39MPa, and feed rate of 32ml/min, and the microcapsules were collected. After cooling, 329g of microcapsules were obtained.

Industrial applicability

实验例Experimental example 1 1 微囊形态及粒径分布Microcapsule morphology and particle size distribution

1. Morphology: Take an appropriate amount of the microcapsule samples of Example 5 and Example 11, place them in an evaporating dish, and place them in natural light or a room equivalent to natural light to observe their color and shape. The microcapsule sample was observed to be white or off-white powder, loose, no bad smell, good fluidity, good dispersibility and stability.

Add a small amount of acetone to the above samples, ultrasonic for 2 minutes (to disperse the overlapping and adhered microcapsules), dip and drop on the glass slide, add a cover glass, and place it on the Winner99C static particle imager (Jinan Micro Nano Particle Instrument Co., Ltd. Company) Observed at 1000 times magnification. Except for individual dents on the surface of the microcapsule particles, the particles are relatively round and close to spherical, and the surface is compact and non-porous, basically free of adhesion, which meets the requirements of microcapsules.

2. Particle size distribution: Take about 0.03 g of the microcapsule samples of Example 5 and Example 11, use 50% ethanol as the dispersion medium, and set the Winner2005B intelligent laser particle size analyzer (Jinan Micronano Particle Instrument Co., Ltd.) to determine the particle size. Diameter (D), the results are shown in Table 1 (D10, D50, D90 in the table represent the equivalent diameter of the largest particle when the cumulative distribution in the distribution curve is 10%, 50%, and 90%, respectively. Dav represents the average particle diameter. The table below is the same ) And Figure 1 and Figure 2.

It can be seen from Figure 1 and Figure 2 that the particle size distribution of the laxative microcapsules of Shouhui is relatively uniform, most of which are concentrated in the vicinity of 20μm. The average particle size of the microcapsules of Example 5 is 22.69μm, and that of the microcapsules of Example 11 The average particle size is 23.03μm, the particle size distribution of the microcapsules of the two samples is relatively narrow, and the distribution is approximately normal, and the microencapsulation effect is better.

实验例Experimental example 2 2 首荟通便微囊包封率测定Determination of the encapsulation rate of Shouhui laxative microcapsules

Encapsulation rate refers to the percentage of the actual drug content in the microcapsule to the total drug content (ie, drug loading) in the microcapsule sample, that is, the percentage of the drug content of the prepared microcapsule to the total drug content of the system. The higher the encapsulation rate, the better the degree of drug encapsulation. The specific method for determining the encapsulation rate of Shouhui laxative microencapsulation is as follows.

Chromatographic conditions and system suitability test Use octadecyl-bonded silica gel as filler; use acetonitrile-methanol-water=20:8:72 as mobile phase; detection wavelength is 320nm. The number of theoretical plates should not be less than 2000 calculated based on the peak of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside.

Preparation of reference solution Accurately weigh an appropriate amount of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside reference substance, add dilute ethanol to make a solution containing 0.06mg per 1ml, and get it.

Preparation of test solution Accurately weigh an appropriate amount of Shouhui laxative microcapsule sample, place it in a 100mL volumetric flask, dilute to 100mL with 75% ethanol, and shake it up so that all the Shouhui laxative extract on the outer surface of the microcapsule is dissolved in the ethanol solution. Pipette 10ml of the above solution into another 25ml volumetric flask, and dilute to the mark with 75% ethanol solution, take 5ml sample solution, transfer to a separatory funnel, extract twice with ether, 15ml each time, discard the ether Then adjust the pH value to 1-2 with dilute hydrochloric acid, extract with ethyl acetate (15ml, 15ml, 15ml, 10ml) 4 times, combine the ethyl acetate solution, evaporate to dryness, dissolve the residue with dilute ethanol and transfer to 2ml volume In the bottle, dilute to volume, shake well, and filter to obtain the test solution of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside outside the microcapsule.

In addition, accurately weigh an appropriate amount of Shouhui laxative microcapsule sample, place it in a 100mL volumetric flask, dissolve it with a pH=7.6 potassium dihydrogen phosphate-sodium hydroxide buffer solution and dilute to 100mL, shake it well, so that the outer surface of the microcapsule is All the laxative extracts of Shouhui in the microcapsules are dissolved in the buffer, and the rest of the operations are the same as above to obtain the microcapsules 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside. Test solution.

Assay Take the standard solution and the test solution, respectively inject 20ul samples, and use the external standard two-point method to calculate the 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucose in the sample The content of glycosides, calculated by the content of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside The amount of fine powder of the extract (M).

Encapsulation rate = (total drug amount in the microcapsule sample M−the amount of drug outside the microcapsule m)×100%/total drug amount M in the microcapsule sample.

From Table 2, when the plasticizer is a compound of polyethylene glycol 6000 and citric acid, and the dosage is fixed at 3.9% of the total formulation formula, as the ratio of polyethylene glycol 6000 to citric acid changes, the first The encapsulation rate of Hui laxative microcapsules and the yield of qualified microcapsules also change accordingly. From the experimental results, when polyethylene glycol 6000: citric acid = 3:1, the encapsulation rate is the best, and the finished product yields The rate is the highest, and is significantly higher than Comparative Example 1 where the plasticizer is a single-flavor polyethylene glycol 6000 and Comparative Example 2 where the plasticizer is a single-flavor citric acid.

The encapsulation rates of the microcapsules obtained in Comparative Example 7 and Comparative Example 8 were poor, 44.1% and 37.6%, respectively; the yields were low, 24.5% and 32.9%, respectively. It can be seen that the encapsulation rate and product yield of Shouhui laxative capsules prepared by the prior art microcapsule preparation formula and microcapsule preparation method cannot meet the corresponding requirements, and industrial production cannot be realized.

实验例Experimental example 3 3 体外累积溶出度试验In vitro cumulative dissolution test

Example 5 of the present invention Shouhui laxative microcapsules, Example 11 Shouhui laxative microcapsule tablets and Shouhui laxative capsules (Lunan Houpu Pharmaceutical Co., Ltd., specifications: 0.35g/capsule×6 capsules/box, Batch number: 26190032) Refer to the dissolution test method (Chinese Pharmacopoeia 2015 Edition Four General Principles 0931 Sustained Release or Controlled Release Preparation) in 250ml phosphate buffer (pH6.8) as the dissolution medium, and the temperature of the water bath is 37℃±0.5℃, The in vitro dissolution test was carried out at a speed of 100r˙min ^-1 , with 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (C ₂₀ H ₂₂ O ₉ ) as an indicator Conduct an inspection.

Preparation of test solution Take 10ml of samples at each time point and add 10ml of distilled water at the same temperature at the same time. The sample is filtered through 0.45μm microporous membrane. 5ml of the additional filtrate is transferred to the separatory funnel. Extracted twice with ether, 15ml each time, discarded Remove the ether solution, adjust the pH to 1-2 with dilute hydrochloric acid, extract with ethyl acetate (15ml, 15ml, 15ml, 10ml) 4 times, combine the ethyl acetate solution, evaporate to dryness, and dissolve the residue with dilute ethanol and transfer to In a 2ml measuring flask, make the volume constant, shake well, filter, and get ready.

Assay Take the standard solution and the sample solution, respectively inject 20ul, and use the external standard two-point method to calculate the logarithmic equation of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside Calculate the cumulative dissolution percentage of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside at each time point. The results are shown in Table 3.

Take the dissolution time (min) as the abscissa and the cumulative dissolution percentage (%) as the ordinate to draw the dissolution curve, see Figure 3. It can be seen from Figure 3 that the cumulative dissolution rate of Shouhui laxative microcapsule capsules and Shouhui laxative microcapsule tablets within 1 hour is less than 54%, and both reached more than 82% dissolution within 2 hours, and the release is basically complete within 3 hours. Shouhui laxative microcapsule preparation has a certain slow-release effect.

实验例Experimental example 4 4 加速稳定性考察Accelerated stability investigation

Two batches of samples of the present invention (Example 5 microcapsules, Example 11 microcapsule tablets) are stored in an aluminum-plastic package (6 tablets/plate) in an accelerated test box (40±2℃, RH75%±5). Months, samples were taken at 0 months, 1 month, 2 months, 3 months, and 6 months respectively) for accelerated stability testing. The stilbene glycoside content determination method is the same as that of Experimental Example 2, and the testing methods for other indicators Refer to the four volumes of the 2015 edition of the Chinese Pharmacopoeia. The accelerated stability test data of the two batches of products are shown in Table 4 and Table 5.

The results of accelerated stability test in Table 4 and Table 5 show that when placed for 6 months under accelerated test conditions (40±2℃, RH75%±5), the properties of Shouhui laxative microcapsule capsules and microcapsule tablets have no change, and the content has no change. Obvious changes, moisture, disintegration (dissolution) time limit and various inspection indicators of hygiene meet the requirements. It can be known from the above accelerated stability test results that the Shouhui laxative microcapsule preparation prepared by the present invention has good stability and controllable quality.

Claims

A Shouhui laxative microcapsule preparation, characterized in that, in terms of weight percentage, the microcapsule preparation formula includes the following ingredients:

A. Shouhui laxative extract fine powder 13.5%-27.5% B. Capsule material 67%-81%

C. Anti-sticking agent 0.9%-2.5% D. Plasticizer 3.6%-5.0%

The capsule material is a kind of gum arabic, maltodextrin, modified starch, octenyl succinate starch, dry starch syrup powder, sodium caseinate, β-lactoglobulin, soy protein isolate, and xanthan gum Or several; the anti-sticking agent is one or more of glycerol monostearate, stearyl alcohol, micronized silica gel, and titanium dioxide; the plasticizer is glycerin, polyethylene glycol 6000, polyethylene glycol One or more of alcohol 400, propylene glycol, and citric acid.
The microcapsule preparation according to claim 1, wherein the fine powder of Shouhui laxative extract is made of the following raw materials: 60-150 parts by weight of Polygonum multiflorum, 100-200 parts by weight of aloe, and 80-180 parts by weight of Cassia seed Parts, 20-80 parts by weight of ginseng, 30-100 parts by weight of wolfberry, 30-100 parts by weight of donkey-hide gelatin, 80-150 parts by weight of Citrus aurantium, 20-80 parts by weight of Baizhu;

Preferably, the fine powder of Shouhui laxative extract is made from the following raw materials: 120 parts by weight of Polygonum multiflorum, 160 parts by weight of aloe, 140 parts by weight of cassia, 50 parts by weight of ginseng, 75 parts by weight of wolfberry, and 75 parts by weight of donkey-hide gelatin , Citrus aurantium 120 parts by weight, and Atractylodes macrocephala 50 parts by weight.
The microcapsule preparation according to claim 1 or 2, characterized in that, in terms of weight percentage, the preparation formula contains the following ingredients: A, Shouhui laxative extract fine powder 17.5%-23.5% B. Capsule material 71.5%-77.5% C. Anti-sticking agent 1.1%-1.9% D. Plasticizer 3.8%-4.7%; the preferred one, in terms of weight percentage, the formulation contains the following ingredients: A, Shouhui laxative extract fine powder 19.7%-22.5 % B, bag material 72.3%-74.1% C. Anti-sticking agent 1.3%-1.8% D. Plasticizer 3.9%-4.4%; the capsule material is sodium complex protein by weight: starch syrup dry powder = 3:2, maltodextrin: β-lactosphere Protein=3:2, Maltodextrin: Soy protein isolate: Modified starch: Arabic gum=5:3:2:1 or octenyl succinate starch: β-lactoglobulin=3:2 The anti-sticking agent is stearyl alcohol by weight: titanium dioxide = 2:1 or glyceryl monostearate; the plasticizer is polyethylene glycol 6000 by weight: citric acid = 2-6:1 Or propylene glycol.
The preparation method of Shouhui laxative microcapsule preparation according to any one of claims 1 to 3, characterized by comprising the following steps: 1) extraction and purification process

A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, sieving, and set aside;

B. Ginseng, Polygonum multiflorum, Cassia Seeds and Aloe are refluxed and extracted twice with 50%-70% ethanol, the first time is 10 times the amount, the second time is 8 times the amount, each 2 hours, respectively, filtered, and the filtrate was combined;

C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the ethanol concentration reach 50%-70% (at 25°C), keep it in the refrigerator for 24-48 hours, Filter

D. The alcohol extract of step B is combined with the decoction of step C, concentrated into a thick paste with a relative density of 1.30 to 1.35 (at 70°C), dried, crushed into fine powder, sieved, and set aside;

E. Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use;

2) Preparation process

F. Weigh the laxative extract powder, capsule material, anti-adhesive agent and plasticizer of step E according to the formula quantity, add the capsule material, anti-adhesive agent and plasticizer to purified water at 45℃-58℃ Under heating and stirring to dissolve, configure it into a 22%-42% mass fraction of capsule material solution, cool to room temperature, add the fine powder of Shouhui laxative extract and emulsifier under stirring, homogenize and emulsify to obtain an emulsified liquid, and set aside ；

G. Step F The emulsion is spray-dried under the conditions of inlet air temperature of 165°C-175°C, spray pressure of 0.36MPa-0.42MPa, and feed rate of 15ml/min-25ml/min, collect the microcapsules, and cool to obtain.
The method according to claim 4, wherein step 1) said extraction and purification process comprises the following steps:

A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, pass through a 150-200 mesh sieve, and set aside;

B. Ginseng, Polygonum multiflorum, Cassia seeds and Aloe are refluxed with 60% ethanol for two extractions, 10 times the amount for the first time, and 8 times the amount for the second time, for 2 hours each time, filter separately, and combine the filtrate;

C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.10-1.20 (at 80°C), put it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;

D. Combine the alcohol extract of step B with the decoction of step C, concentrate into a thick paste with a relative density of 1.30 to 1.35 (70°C), dry with belt vacuum, pulverize into fine powder, sieved, and set aside;

E. Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use.
The method according to claim 5, characterized in that the conditions of the belt vacuum drying in step 1) D are vacuum degree -0.08MPa-0.10Mpa, and drying temperature 50°C-60°C.
The method according to any one of claims 4-6, characterized in that step 2) the preparation process comprises the following steps: F. Weighing step E according to the amount of the formula. , Anti-sticking agent and plasticizer, add the capsule material, anti-sticking agent and plasticizer to purified water, heat and stir at 52℃ to dissolve, configure into a capsule material solution with a mass fraction of 36%, cool to room temperature, and stir In the state, add the fine powder of Shouhui laxative extract and emulsifier, homogenize and emulsify to obtain the emulsified liquid for use;

G. Step F The emulsion is spray-dried under the conditions of an inlet air temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min, collects the microcapsules, and cools them to obtain.
The method of claim 7, wherein the emulsifier in step F is one or more of Tween 80, soybean phospholipid, lecithin, poloxamer, and sucrose fatty acid ester, and the amount is calculated by mass fraction It is 0.4%-1.2% of the total preparation formula.
The method according to claim 8, wherein the emulsifier in step F is a composite emulsifier of soybean phospholipid: sucrose fatty acid ester = 4:6 in weight ratio, and the amount is calculated as the mass fraction of the total formulation formula Of 0.9%.
The method according to claim 1, wherein step 1) said extraction and purification process comprises the following steps: 1) extraction and purification process

A. Weigh the donkey-hide gelatin according to the formula, crush it into superfine powder, pass through a 150-200 mesh sieve, and set aside;

B. Ginseng, Polygonum multiflorum, Cassia seeds and Aloe are refluxed with 60% ethanol for two extractions, 10 times the amount for the first time, and 8 times the amount for the second time, for 2 hours each time, filter separately, and combine the filtrate;

C. Add medlar, Citrus aurantium, and Atractylodes macrocephala to decoct twice with water, add 8 times the amount of water for the first time, soak for 1 hour, decoct for 1.5 hours, add 6 times the amount of water for the second time, decoct for 1.5 hours, filter, Combine the filtrate and concentrate it into a clear paste with a relative density of 1.15 (at 80°C), place it at room temperature, stir and add ethanol to make the concentration reach 60% (at 25°C), keep it in the refrigerator for 36 hours, and filter;

D. Combine the alcohol extract of step B with the decoction of step C, concentrate into a thick paste with a relative density of 1.30 to 1.35 (70°C), vacuum-dry it with -0.09pa, pulverize into fine powder, sieving, and set aside;

E. Mix the superfine powder of donkey-hide gelatin in step A and the fine powder in step D to obtain the fine powder of laxative extract of Shouhui, for use;

2) Preparation process

F. Take the laxative extract powder, capsule material, anti-sticking agent and plasticizer of step E, add the capsule material, anti-sticking agent and plasticizer to purified water, heat and stir at 52℃ to dissolve, configure Into a capsule material solution with a mass fraction of 36%, cool to room temperature, add the fine powder of Shouhui laxative extract and a composite emulsifier of soybean phospholipid: sucrose fatty acid ester = 4:6 under stirring, and the amount is calculated by mass fraction This is 0.9% of the total formulation formula. , Homogeneous emulsification to obtain the emulsion for use;

G. Step F The emulsion is spray-dried under the conditions of an inlet air temperature of 172°C, a spray pressure of 0.39 MPa, and a feed rate of 22.5 ml/min, collects the microcapsules, and cools them to obtain.