A preparation process of a new type of Liangxue Shiwei tablets

Abstract

The present invention relates to the field of pharmaceutical production, and discloses a preparation process of a new type of Liangxue Shiwei tablets. The prescription of the Liangxue Shiwei tablets is as follows: 89.3 g of Lithospermum erythrorhizon, 89.3 g of Gypsum Fibrosum (cool-processed), 35.7 g of Aucklandia lappa, 35.7 g of Picrorhiza scrophulariiflora, 53.6 g of Dianthus superbus, 35.7 g of Gypsum Fibrosum, 53.6 g of Carthamus tinctorius, 35.7 g of Glycyrrhiza uralensis, 35.7 g of Inula helenium, and 35.7 g of Glehnia littoralis. The preparation steps are as follows: S01 According to the prescription, the above 8 herbs including Lithospermum erythrorhizon, Gypsum Fibrosum (cool-processed), Aucklandia lappa, Picrorhiza scrophulariiflora, Dianthus superbus, Gypsum Fibrosum, Carthamus tinctorius, and Inula helenium, and the other 2 herbs including Glehnia littoralis and Glycyrrhiza uralensis are jointly pulverized into fine powder, screened, and mixed evenly for standby; S02 Granulate the fine powder of the drugs evenly mixed in the above S01 through an adhesive, press into tablets, coat the tablets, and the drying temperature is 20-70 °C for 2-6 hours; the adhesive is one or more of the water decoction of the 2 herbs including Glehnia littoralis and Glycyrrhiza uralensis, 1%-10% sodium carboxymethylcellulose solution, and 5%-20% polyvinylpyrrolidone k30 solution. This new process increases the binding effect of granulation, finally improves the tablet quality of the Liangxue Shiwei tablets, ensures the qualified rate of first-class products, eliminates repetitive operations such as rework, and improves labor productivity.

Description

Technical Field

[0001] The invention relates to the field of medicine production, and in particular to a preparation process of a Liangxue Shiwei tablet. Background Art

[0002] Chinese medicine tablets refer to preparations in the form of round or special-shaped tablets made by mixing and compressing medicinal material extracts, medicinal material extracts and medicinal material powders, or medicinal material powders and suitable excipients. Due to its complex composition, Chinese medicine often contains a large amount of starch, cellulose and other ingredients, which are usually difficult to granulate. The prepared granules have poor fluidity or low adhesion and are difficult to tablet. This is also a key factor affecting the difficulty in controlling the production quality of Chinese medicine tablets compared to chemical medicine tablets. Among Chinese medicine dosage forms, the disintegration and bioavailability of tablets are generally better than those of pills. The dosage is accurate, the drug content difference is small, and the stability of coated tablets is better than other traditional Chinese medicine tablets.

[0003] Liangxue Shiwei Tablets are Mongolian medicine. They are composed of Lithospermum officinale, Hanshuishi (cold-processed), Aucklandia lappa, Coptis chinensis, Dianthus superbus, Gypsum, Safflower, Licorice, Inula japonica, and Adenophora chinensis. They have the effects of cooling blood and improving eyesight. They are used for liver fire, lung heat, headache and red eyes in the middle of the "Bao Ri" period. The original preparation method of Liangxue Shiwei Tablets is to use raw powder as medicine and purified water as adhesive for granulation. Due to the difference in moisture content of the incoming medicinal materials, sometimes the viscosity of the adhesive is insufficient during the granulation process, resulting in insufficient tablet hardness, and the coating quality cannot be effectively guaranteed, or even impossible to coat, which directly affects the quality of the appearance of the film-coated tablets and affects the market promotion of the exclusive product. Summary of the invention

[0004] Prescription for Liangxue Shiwei Tablets: Lithospermum officinale 89.3g, Hanshuishi (cold-processed) 89.3g, Aucklandia 35.7g, Picrorhizon 35.7g, Dianthus superbus 53.6g, Gypsum 35.7g, Safflower 53.6g, Licorice 35.7g, Inula 35.7g, Adenophora 35.7g

[0005] Original preparation method: The above 10 ingredients are crushed into fine powder, sieved, mixed, granulated with water as a binder, pressed into 1000 tablets, and film-coated; the tablets are not hard enough, the appearance is not smooth after coating, and some batches cannot be coated.

[0006] Tablet quality: check weight difference ±4.5%; hardness: there is a crisp sound when breaking by hand; appearance: the shape is complete and uniform, and the color is consistent; disintegration time (after coating): check the disintegration time of 50min.

[0007] In view of the limitations existing in the tablet preparation process of Liangxue Shiwei Tablets, during the process of one-time tablet production, due to the differences in the moisture content of the medicinal materials, sometimes the viscosity of the binder is insufficient during the granulation process, resulting in insufficient hardness of the tablets and even inability to coat. The first-class product qualification rate fails to reach 100%. Often, it cannot be released due to the not-so-smooth appearance, causing some rework to meet the standards, which is time-consuming and laborious, and the forming rate is 80 - 90%. The processing is time-consuming, with serious waste and too high costs. Based on the effects of the above process research, according to the characteristics of the prescription medicinal materials, different binders were selected for comparative research, including purified water, the drug itself, polyvinylpyrrolidone K30, and sodium carboxymethylcellulose, to optimize and determine their advantages and disadvantages.

[0008] Meanwhile, under the principle of not changing the material basis, the present invention utilizes the viscosity of Glehnia littoralis and Glycyrrhiza glabra in the prescription to change the viscosity during the granulation process to facilitate forming. The new process uses the physical method of the drug itself to increase the binding effect of granulation, ultimately improving the tablet quality of Liangxue Shiwei Tablets, ensuring the first-class product qualification rate, eliminating repetitive operations such as rework, and improving labor productivity.

[0009] Based on the above research, the present invention was completed.

[0010] First, the present invention provides a new method for preparing Liangxue Shiwei Tablets. The prescription of the Liangxue Shiwei Tablets is as follows: Lithospermum erythrorhizon 89.3 g, Gypsum Fibrosum (processed with coolness) 89.3 g, Aucklandia lappa 35.7 g, Picrorhiza scrophulariiflora 35.7 g, Dianthus superbus 53.6 g, Gypsum Fibrosum 35.7 g, Carthamus tinctorius 53.6 g, Glycyrrhiza glabra 35.7 g, Inula helenium 35.7 g, Glehnia littoralis 35.7 g. The preparation steps are as follows:

[0011] S01 According to the prescription, the above 8 herbs including Lithospermum erythrorhizon, Gypsum Fibrosum (processed with coolness), Aucklandia lappa, Picrorhiza scrophulariiflora, Dianthus superbus, Gypsum Fibrosum, Carthamus tinctorius, and Inula helenium and the 2 herbs Glehnia littoralis and Glycyrrhiza glabra are respectively pulverized into fine powders, screened, and mixed evenly for standby.

[0012] S02 Granulate the evenly mixed drug fine powders in S01 through a binder, press into tablets, coat the tablets, and dry them. The drying temperature is 20 - 70 °C and the time is 2 - 6 hours.

[0013] Furthermore, the binder is one or more of the aqueous decoction binder of the 2 herbs Glehnia littoralis and Glycyrrhiza glabra, the 1% - 10% sodium carboxymethylcellulose solution binder, and the 5% - 20% polyvinylpyrrolidone K30 solution binder.

[0014] In one embodiment, when the binder is preferably the aqueous decoction of the 2 herbs Glehnia littoralis and Glycyrrhiza glabra, the standby mixed drug fine powders in S01 only include the fine powders of the above 8 herbs including Lithospermum erythrorhizon, Gypsum Fibrosum (processed with coolness), Aucklandia lappa, Picrorhiza scrophulariiflora, Dianthus superbus, Gypsum Fibrosum, Carthamus tinctorius, and Inula helenium.

[0015] Furthermore, the water decoction binder of the two herbs Glehniae Radix and Glycyrrhizae Radix is prepared by pulverizing the two herbs Glehniae Radix and Glycyrrhizae Radix in the prescription into fine powder, adding 300 - 1000 ml of water, extracting at a temperature of 30 - 90°C for 2 - 9 hours, and then cooling, which is the water decoction of Glehniae Radix and Glycyrrhizae Radix.

[0016] In another embodiment, when the binder is a 1% - 10% sodium carboxymethylcellulose solution binder and / or a 5% - 20% povidone k30 solution binder, the fine powder of the mixed drugs reserved in S01 includes ten herbs: Lithospermi Radix, Gypsum Fibrosum (cooled), Aucklandiae Radix, Picrorhizae Rhizoma, Dianthi Herba, Gypsum Fibrosum, Carthami Flos, Inulae Radix, Glehniae Radix, and Glycyrrhizae Radix.

[0017] Second, the present invention provides a new Liangxue Shiwei Tablet. The prescription of the new Liangxue Shiwei Tablet is as follows: Lithospermi Radix 89.3 g, Gypsum Fibrosum (cooled) 89.3 g, Aucklandiae Radix 35.7 g, Picrorhizae Rhizoma 35.7 g, Dianthi Herba 53.6 g, Gypsum Fibrosum 35.7 g, Carthami Flos 53.6 g, Glycyrrhizae Radix 35.7 g, Inulae Radix 35.7 g, Glehniae Radix 35.7 g; it is obtained by the following steps:

[0018] S01 Pulverize the above eight herbs Lithospermi Radix, Gypsum Fibrosum (cooled), Aucklandiae Radix, Picrorhizae Rhizoma, Dianthi Herba, Gypsum Fibrosum, Carthami Flos, and Inulae Radix and the two herbs Glehniae Radix and Glycyrrhizae Radix into fine powder respectively according to the prescription, sieve, and mix evenly for standby;

[0019] S02 Granulate the fine powder of the drugs mixed evenly in S01 through a binder, press into tablets, coat the tablets, and dry them. The drying temperature is 20 - 70°C and the time is 2 - 6 hours.

[0020] Furthermore, the binder is one or more of the water decoction binder of the two herbs Glehniae Radix and Glycyrrhizae Radix, a 1% - 10% sodium carboxymethylcellulose solution binder, and a 5% - 20% povidone k30 solution binder.

[0021] In one embodiment, when the binder is preferably the water decoction of the two herbs Glehniae Radix and Glycyrrhizae Radix, the fine powder of the mixed drugs reserved in S01 only includes the fine powder of eight herbs: Lithospermi Radix, Gypsum Fibrosum (cooled), Aucklandiae Radix, Picrorhizae Rhizoma, Dianthi Herba, Gypsum Fibrosum, Carthami Flos, and Inulae Radix.

[0022] Furthermore, the water decoction binder of the two herbs Glehniae Radix and Glycyrrhizae Radix is prepared by pulverizing the two herbs Glehniae Radix and Glycyrrhizae Radix in the prescription into fine powder, adding 300 - 1000 ml of water, extracting at a temperature of 30 - 90°C for 2 - 9 hours, and then cooling, which is the water decoction of Glehniae Radix and Glycyrrhizae Radix.

[0023] In another embodiment, when the adhesive is a 1% to 10% sodium carboxymethylcellulose solution adhesive and / or a 5% to 20% povidone k30 solution adhesive, the fine powder of the mixed drug reserved in S01 includes 10 herbs, namely lithospermum root, gypsum rubrum (cooled), costus root, picrorhiza rhizome, dianthus superbus, gypsum, safflower, elecampane root, glehnia root and licorice root. Detailed implementation mode

[0024] The powders described herein are classified as follows:

[0025] Coarsest powder: It refers to the powder that can all pass through the No. 1 sieve, but is mixed with no more than 20% of the powder that can pass through the No. 3 sieve;

[0026] Coarse powder: It refers to the powder that can all pass through the No. 2 sieve, but is mixed with no more than 40% of the powder that can pass through the No. 4 sieve;

[0027] Medium powder: It refers to the powder that can all pass through the No. 4 sieve, but is mixed with no more than 60% of the powder that can pass through the No. 5 sieve;

[0028] Fine powder: It refers to the powder that can all pass through the No. 5 sieve and contains no less than 95% of the powder that can pass through the No. 6 sieve;

[0029] Finest powder: It refers to the powder that can all pass through the No. 6 sieve and contains no less than 95% of the powder that can pass through the No. 10 sieve;

[0030] Extra-fine powder: It refers to the powder that can all pass through the No. 8 sieve and contains no less than 95% of the powder that can pass through the No. 9 sieve.

[0031] The corresponding sieves are as follows:

[0032] No. 4 sieve: 250um ± 9.9um, 65 meshes; No. 5 sieve: 180um ± 7.6um, 80 meshes; No. 6 sieve: 150um ± 6.6um, 100 meshes; No. 7 sieve: 125um ± 5.8um, 120 meshes; No. 8 sieve: 90um ± 4.6um, 150 meshes; No. 9 sieve: 75um + 4.1um, 200 meshes.

[0033] The term "disintegration time limit" used herein refers to the time when an oral solid preparation completely disintegrates, dissolves or becomes fragmented under specified conditions. Except for insoluble coating materials or broken capsule shells, it should all pass through the sieve. If a small amount cannot pass through the sieve, but has softened or floated lightly and has no hard core, it can be regarded as meeting the requirements.

[0034] The term "tablet hardness" used in this article refers to the hardness of Chinese medicine tablets, which generally refers to their compressive strength, that is, the radial crushing force of the tablet. Hardness is not a simple physical concept but a comprehensive indicator of mechanical properties such as material elasticity, plastic strength and toughness. The test method for tablet hardness is to take 20 tablets of the test sample and put them into the sample slot of the tablet hardness tester in turn for manual tablet compression, read and record the maximum pressure when the tablet is broken, which is the tablet hardness of each tablet; the hardness of coated tablets is more suitable when it is 4 to 6 kg, that is, 40 to 60 N; generally, Chinese medicine tablets that can withstand a pressure of 40 to 60 N are considered qualified, and 40 to 60 N is generally more suitable for coating Chinese medicine tablets.

[0035] The term "friability" used in this article means that tablets are prone to fragmentation, capping, and cracking after being subjected to vibration or friction. Tablet friability reflects the tablet's ability to resist wear and vibration, and is also an important item in the tablet quality standard inspection; inspection method: For tablets weighing 0.65g or less, take a number of tablets to make a total weight of about 6.5g; for tablets weighing more than 0.65g, take 10 tablets. Use a hair dryer to blow away the powder that falls off the tablets, weigh them accurately, place them in a cylinder, and rotate them 100 times. Take them out, remove the powder in the same way, weigh them accurately, and the weight loss should not exceed 1%, and no broken, cracked, or crushed tablets should be detected. This test is generally performed only once. If the weight loss exceeds 1%, it should be repeated twice, and the average weight loss of the three times should not exceed 1%, and no broken, cracked, or crushed tablets should be detected.

[0036] Example 1

[0037] Prescription for Liangxue Shiwei Tablets: Lithospermum officinale 89.3g, Hanshuishi (cold-processed) 89.3g, Aucklandia 35.7g, Picrorhizon 35.7g, Dianthus superbus 53.6g, Gypsum 35.7g, Safflower 53.6g, Licorice 35.7g, Inula 35.7g, Adenophora 35.7g

[0038] Preparation method:

[0039] 1. Grind the other eight herbs except Adenophora adenophora and Licorice into fine powder, sieve and mix well;

[0040] 2. Preparation of liquorice and Glehnia littoralis decoction: weigh 35.7g Glehnia littoralis and 35.7g liquorice, grind them into fine powder, add 300-1000ml of water, extract at 35°C for 4 hours, cool, and obtain liquorice and Glehnia littoralis decoction (including the residue);

[0041] 3. Use the above-mentioned boiled liquid as a binder to make granules, and dry them (temperature 45°C) for 6 hours;

[0042] 4. Whole granules, tablet pressing into 1000 tablets, film coating. One-time forming rate is over 97%, saving time and effort.

[0043] 5. Quality inspection: The weight difference meets the requirements, the tablet hardness is 51.0 - 61.5 Newtons, and the friability is 0.74%; the appearance is complete and uniform, and the color is consistent; the disintegration time limit is inspected to be 45 minutes.

[0044] Example 2

[0045] Prescription of Liangxue Shiwei Tablets: Lithospermum erythrorhizon 89.3g, Gypsum Fibrosum (processed with coolness) 89.3g, Aucklandia lappa Decne. 35.7g, Picrorhiza scrophulariiflora Pennell 35.7g, Dianthus superbus L. 53.6g, Gypsum Fibrosum 35.7g, Carthamus tinctorius L. 53.6g, Glycyrrhiza uralensis Fisch. 35.7g, Inula helenium L. 35.7g, Glehnia littoralis Fr. Schmidt ex Miq. 35.7g

[0046] 1. Grind the above 10 herbs into fine powder, sieve, mix evenly, and reserve for use;

[0047] 2. Dissolve 2.8 kg of polyvinylpyrrolidone K30 in 100 kg of water with stirring and stir for 2 hours to obtain a polyvinylpyrrolidone K30 solution of about 7.4%.

[0048] 3. Granulate using the above-mentioned polyvinylpyrrolidone K30 solution of about 7.4% as the binder, and dry (temperature 55°C) for 4 hours;

[0049] 4. Screen the granules, press into 1000 tablets, and coat with film coating. The one-time forming rate is over 95%, saving time and effort.

[0050] 5. Quality inspection: The weight difference meets the requirements, the tablet hardness is 42.0 - 55.0 Newtons, and the friability is 0.87%; the appearance is complete and uniform, and the color is consistent; the disintegration time limit is inspected to be 45 minutes.

[0051] Example 3

[0052] Prescription of Liangxue Shiwei Tablets: Lithospermum erythrorhizon 89.3g, Gypsum Fibrosum (processed with coolness) 89.3g, Aucklandia lappa Decne. 35.7g, Picrorhiza scrophulariiflora Pennell 35.7g, Dianthus superbus L. 53.6g, Gypsum Fibrosum 35.7g, Carthamus tinctorius L. 53.6g, Glycyrrhiza uralensis Fisch. 35.7g, Inula helenium L. 35.7g, Glehnia littoralis Fr. Schmidt ex Miq. 35.7g

[0053] 1. Grind the above 10 herbs into fine powder, sieve, mix evenly, and reserve for use;

[0054] 2. Granulate using about 5% sodium carboxymethylcellulose solution as the binder, and dry (temperature 55°C) for 5 hours;

[0055] 3. Screen the granules, press: press into 1000 tablets, and coat with film coating. The one-time forming rate is over 90%, saving time and effort.

[0056] 4. Quality inspection: The weight difference meets the requirements, the tablet hardness is 30.0 - 40.0 Newtons, and the friability is 0.94%; the appearance is complete and uniform, and the color is consistent; the disintegration time limit is inspected to be 40 minutes.

[0057] Judgment: The hardness of the tablets made by this method is insufficient and the film coating is unqualified.

[0058] Example 4

[0059] Prescription of Liangxue Shiwei Tablets: Lithospermum erythrorhizon 89.3g, Gypsum Fibrosum (cooled) 89.3g, Aucklandia lappa 35.7g, Picrorhiza scrophulariiflora 35.7g, Dianthus superbus 53.6g, Gypsum Fibrosum 35.7g, Carthamus tinctorius 53.6g, Glycyrrhiza uralensis 35.7g, Inula helenium 35.7g, Glehnia littoralis 35.7g

[0060] 1. Grind the above 10 herbs into fine powder, sieve, mix well, and reserve for use.

[0061] 2. Use about 1% sodium carboxymethylcellulose as the binder to granulate, and dry (temperature 55°C) for 5 hours.

[0062] 3. Screen the granules and press tablets (punch pressure 8.5 kg) to make 1000 tablets.

[0063] 4. After crushing the tablets, press them dry. Repeat twice.

[0064] 5. Press tablets: Press to make 1000 tablets and coat them with film coating. The one-time forming rate is over 90%, which is time-saving and labor-saving.

[0065] 6. Quality inspection: The weight difference meets the requirements, the hardness of the tablets is 39.8 - 47.7 N, the friability is 0.97%; the shape is complete and uniform, and the color is consistent; check the disintegration time limit, which is 40 min.

[0066] Judgment: The hardness of the tablets made by this method is insufficient and the film coating is unqualified.

[0067] Based on the above experiments, the one-time forming rate is between 90% and 95%, and there is no improvement in the process effect. The test judgment is unqualified.

Claims

1. A preparation method of Liangxue Shiwei Tablets. The prescription of Liangxue Shiwei Tablets is as follows: Lithospermum erythrorhizon 89.3 g, Cold-processed Gypsum Fibrosum 89.3 g, Aucklandia lappa Decne. 35.7 g, Picrorhiza scrophulariiflora Pennell 35.7 g, Dianthus superbus L. 53.6 g, Gypsum Fibrosum 35.7 g, Carthamus tinctorius L. 53.6 g, Glycyrrhiza uralensis Fisch. 35.7 g, Inula helenium L. 35.7 g, Glehnia littoralis Fr. Schmidt ex Miq. 35.7 g. The preparation steps are as follows: S01. Pulverize the other 8 flavors except Glehnia littoralis Fr. Schmidt ex Miq. and Glycyrrhiza uralensis Fisch. into fine powder according to the above prescription, sieve and mix evenly; S02. Preparation method of the water decoction of Glehnia littoralis Fr. Schmidt ex Miq. and Glycyrrhiza uralensis Fisch.: Weigh 35.7 g of Glehnia littoralis Fr. Schmidt ex Miq. and 35.7 g of Glycyrrhiza uralensis Fisch., pulverize them into fine powder, add 300 - 1000 ml of water, carry out extraction at a temperature of 35°C for 4 hours, and then cool to obtain the water decoction of Glehnia littoralis Fr. Schmidt ex Miq. and Glycyrrhiza uralensis Fisch. containing medicinal residues; S03. Use the above water decoction as a binder to make granules and dry them at a temperature of 45°C for 6 hours; S04. Screen the granules, press them into 1000 tablets, and coat them with film coating.