KR102350374B1 - A tablet with improved disintegration property comprising high content of milk thistle for helping liver health - Google Patents

Abstract

The present invention relates to: a tablet which contains a milk thistle extract, which is a poorly soluble component, in a high content, and has improved disintegration properties since it does not cause a problem of disintegration delay; and a method for manufacturing the same. More specifically, the present invention is a tablet comprising a milk thistle extract, a Cichorium intybus extract, and crystalline cellulose. The present invention is the tablet with improved disintegration property which contains, based on 100 parts by weight of the total tablet, 20 parts by weight or more of the milk thistle extract, 5 to 7.2 parts by weight of the Cichorium intybus extract.

Description

{A tablet with improved disintegration property comprising high content of milk thistle for helping liver health}

The present invention relates to a tablet that exhibits excellent disintegration properties despite containing a high content of non-disintegrating and sparingly soluble components such as milk thistle extract.

Tablets are solid preparations made by compression-molding into a certain shape by uniformly mixing functional raw materials and additives, and have advantages such as ease of handling and intake, accuracy of dosage, and stability of raw material indicators. It is one of the most productive formulations among food formulations.

In order for the active ingredient (main ingredient) contained in the tablet to be sufficiently absorbed into the body, the tablet disintegrates in the digestive tract after the tablet is ingested and the active ingredient must be released into the digestive tract fluid. corresponds to

As a method for improving the disintegration property of the tablet, there may be a method of increasing the content of excipients and reducing the amount of an active ingredient (main ingredient) that delays disintegration, or there may be a method of using a disintegrant. However, in the case of the method of lowering the content of the active ingredient, the amount of the tablet to be administered increases as the amount of the active ingredient contained per tablet decreases, which may cause inconvenience to consumers or patients who consume it, and the unit price is high. There is this. In addition, as consumers' negative perception and rejection of additives are increasing, research on a technology capable of improving the disintegration properties of tablets without using a disintegrant or reducing its amount is required.

On the other hand, milk thistle has silymarin as the main functional ingredient and is a health functional food notified raw material that can help liver function. Most of silver is a solid product, and in particular, a high proportion is produced in the form of a tablet product. In the case of milk thistle products manufactured as tablets, the disintegration quality is improved by adding a disintegrant or a large amount of excipients because the milk thistle extract does not disintegrate well due to the poorly soluble nature of the extract. will do Korean Patent Application Laid-Open No. 2009-0086686 uses a dissolution enhancer, a drug support, and a disintegrant to solve the problem of silymarin, a poorly soluble substance, in a pharmaceutical composition containing silymarin, so a disintegrant such as crospovidone is essential. There is still the problem of adding In Korea Patent Publication No. 2015-0063017, a separate liquid composition is prepared on the outside of the tablet in order to improve its disintegration, storage stability, efficacy, etc. in providing a tablet containing ingredients such as milk thistle extract. Although the method of packaging in the same container is used, there is a disadvantage that the above effect does not occur in a single tablet.

Therefore, the content of the milk thistle extract, which is a poorly soluble component, may not be lowered, and there is an urgent need for research on tablets with improved disintegration properties while not adding or reducing the amount of a disintegrant component.

An object of the present invention is to provide a tablet that contains milk thistle extract, which is a poorly soluble component, but does not cause a problem of disintegration time delay.

In addition, an object of the present invention is to provide a method for preparing a tablet having improved disintegration as described above.

In order to achieve the above object, one aspect of the present invention is a milk thistle extract; And chicory extract; provides a tablet containing.

Another aspect of the present invention provides a method for preparing a tablet, including; mixing the extract of milk thistle and chicory extract.

Although the tablet of the present invention and the tablet prepared by the manufacturing method of the present invention contain milk thistle extract, which is a poorly soluble component, the disintegration rate is fast and the disintegration quality is excellent. In particular, the tablet of the present invention may not contain calcium carboxymethylcellulose or sodium carboxymethylcellulose, which are typically used to aid disintegration, but it shows similar or superior disintegration quality compared to tablets including the above components. .

In addition, the tablet of the present invention provides a tablet containing a milk thistle extract with a high content because the content of the milk thistle extract that can function as an active ingredient is relatively high, while the disintegration time is shortened and the disintegration property is improved. This has the advantage that the amount of tablets that need to be consumed per day can be reduced, and thus the convenience of consumers or patients who need it can be improved.

That is, although the tablet of the present invention contains milk thistle extract in a high content, there is no problem of difficulty or delay in disintegration that may be caused by this, and the disintegration property is improved.

However, the effects of the present invention are not limited to the above-mentioned effects, and other effects not mentioned will be clearly understood by those skilled in the art from the following description.

1 is a process diagram showing the process of manufacturing the tablet of the present invention.
Figure 2 is a comparison of the photos of the appearance of the tablets of Examples 1-4 and Comparative Examples 2-1 to 2-8 and the morphology photos after the tablets were placed in 100 ml of water at 37 ° C. and left for 1 minute. will be.

Hereinafter, the present invention will be described in detail.

1. Tablets with improved disintegration

One aspect of the present invention provides a tablet with improved disintegration while including a poorly soluble component.

The tablet of the present invention, milk thistle extract; and chicory extract.

In the present invention, the term “tablet” means that the powder is formed into a predetermined shape by pressing and tableting, so that the user can easily take it. The powder means an aggregate of solid materials constituting the tablet, and the particle size of the powder may be in the range of about 1-100 μm, but is not limited thereto. The shape of the powder may vary, for example, the powder may be acicular, polygonal, crystalline, dentritic, fibrous, flaky, granular ( It may be formed in granular, irregular, spherical, or the like.

The tablet may be in the form of an uncoated tablet, or in the form of a coated tablet coated with a coating agent. The coating agent may be used without limitation, for example, may be a neocoat (neocoat).

The milk thistle extract may contain silymarin, and may be applied to the present invention regardless of the extraction method thereof. Since silymarin contained in the milk thistle extract is a fat-soluble component, it corresponds to a poorly soluble component that is difficult to dissolve in water, and thus has a problem that it is difficult to disintegrate. It is common to add a large amount of excipients and the like.

The milk thistle extract may be included as an active ingredient in the tablet of the present invention, and the meaning of 'included as an active ingredient' may have the same meaning as being included as a main ingredient or a main ingredient, which is each component constituting the tablet. It may be that the element is included in an amount sufficient to achieve its intended function.

The milk thistle extract may be included in an amount of 20 parts by weight or more based on 100 parts by weight of the total tablet. Specifically, the milk thistle extract contains 20 parts by weight or more, 25 parts by weight or more, 30 parts by weight or more, 35 parts by weight or more, 40 parts by weight or more, 45 parts by weight or more, 50 parts by weight or more, 55 parts by weight or more, 60 parts by weight or more. Parts by weight or more, 65 parts by weight or more, 70 parts by weight or more, 75 parts by weight or more, 80 parts by weight or more, 85 parts by weight or more, 90 parts by weight or more, 95 parts by weight or more, 96 parts by weight or more, 97 parts by weight or more, 98 or more, 99 parts by weight or more, 20 parts by weight to 99 parts by weight, 30 parts by weight to 90 parts by weight, 40 parts by weight to 80 parts by weight, 45 parts by weight to 70 parts by weight, 45 parts by weight to 65 parts by weight or 50 parts by weight It may be included in an amount of to 60 parts by weight, but is not limited thereto. When the milk thistle extract is included in the content within the above range, the function or pharmaceutical function for improving the health function or the pharmaceutical function by the milk thistle extract or the silymarin contained therein can be sufficiently exhibited, for example, the function of improving the liver function can be exhibited. Therefore, the tablet of the present invention may be used for the purpose of improving or preventing liver function or preventing or treating liver disease.

In addition, the content of the milk thistle extract in the above range corresponds to a larger amount compared to conventional milk thistle-containing tablets, and the tablet of the present invention is characterized in that it contains a large amount of milk thistle extract. The tablet of the present invention has improved disintegration properties due to components such as chicory extract, which will be described later, and even if the content of milk thistle extract contained in the tablet is as high as the above range, the problem that the disintegration time becomes too long does not occur. It can have excellent disintegration quality. As the tablet of the present invention contains milk thistle extract in the content within the above range, the content of milk thistle extract or silymarin contained therein is high per tablet, so the number of tablets consumed per day can be reduced. have.

The chicory extract is a material obtained by extracting the chicory using chicory (Cichorium intybus ), and if a material containing a component in chicory, its extraction method, the extracted component, or the form of the extract includes all. The chicory extract may be in the form of a liquid, gel, powder, etc., but is not limited thereto.

The chicory extract may serve to reduce the disintegration time by improving the disintegration property of the tablet, and specifically improve its fluidity and disintegration quality by penetrating water into the granules containing poorly soluble components such as milk thistle extract may be, but is not limited thereto.

The extraction method of the chicory extract may be used without limitation, for example, the chicory extract may be extracted using a solvent. The solvent may be at least one organic solvent selected from the group consisting of alcohols having 1 to 5 carbon atoms, acetone, acetonitrile, ethyl acetate, chloroform, dichloromethane, ethyl ether, xylene and hexane, water, or a mixture thereof. The alcohol having 1 to 5 carbon atoms may be an alcohol having 1 to 4 carbon atoms, 1 to 3 carbon atoms, 2 to 5 carbon atoms, 2 to 4 carbon atoms, 2 to 3 carbon atoms, or 1 to 2 carbon atoms, for example, ethanol, but However, the present invention is not limited thereto. The ethanol may be edible ethanol, and when extraction is performed using the ethanol as a solvent, alcohol widely used commercially may be used.

The chicory extract may be included in an amount of 5 to 7.2 parts by weight based on 100 parts by weight of the total tablet. Specifically, the chicory extract is 5 parts by weight to 7.2 parts by weight, 5.2 parts by weight to 7.2 parts by weight, 5.5 parts by weight to 7.1 parts by weight, 5.7 parts by weight to 7 parts by weight, 5.7 parts by weight to 6.7 parts by weight or 6 to 6.5 parts by weight. It may be included in an amount by weight, but is not limited thereto. When the chicory extract is included in the content within the above range, the function of milk thistle, an active ingredient, may not be inhibited while exhibiting the effect of improving the disintegrability of the tablet.

The tablet of the present invention may further include crystalline cellulose.

The crystalline cellulose not only functions as a stabilizer and emulsifier, but also can help to improve the disintegration properties of the tablet as it is used in the tablet of the present invention together with the chicory extract, thereby exhibiting a synergistic effect.

The crystalline cellulose may be included in an amount of 40 parts by weight to 80 parts by weight based on 100 parts by weight of the milk thistle extract. Specifically, the crystalline cellulose is 40 parts by weight to 80 parts by weight, 45 parts by weight to 80 parts by weight, 50 parts by weight to 78 parts by weight, 55 parts by weight to 78 parts by weight, 60 parts by weight based on 100 parts by weight of the milk thistle extract. It may be included in an amount of parts by weight to 76 parts by weight, 65 parts by weight to 75 parts by weight, or 70 parts by weight to 78 parts by weight, but is not limited thereto. When the crystalline cellulose is included in the content within the above range, there is an advantage that the disintegration time of the tablet can be significantly reduced.

The crystalline cellulose may be included in an amount of 25 to 45 parts by weight based on 100 parts by weight of the total tablet. Specifically, the crystalline cellulose is 25 parts by weight to 45 parts by weight, 28 parts by weight to 45 parts by weight, 30 parts by weight to 43 parts by weight, 35 parts by weight to 42 parts by weight, 38 parts by weight to 100 parts by weight of the total tablet. It may be included in an amount of 41 parts by weight or 38 parts by weight to 40 parts by weight, but is not limited thereto. When the crystalline cellulose is included in the content within the above range, there is an advantage that the disintegration time of the tablet can be significantly reduced.

The tablet of the present invention may be one that does not contain a disintegrant substantially. The disintegrant may be carboxymethylcellulose calcium (Carboxymethylcellulose Calcium), carboxymethylcellulose sodium (Carboxymethylcellulose Sodium), croscarmellose sodium (Croscarmellose Sodium), corn starch (Starch, Corn), etc., and more specifically, the disintegrant is carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, alginic acid, silicified cellulose (Cellulose, Silicified Microcrystalline), powdered cellulose (Cellulose, Powdered), croscarmellose sodium, crospovidone, glycine ), Guar Gum, Low-substituted Hydroxypropyl Cellulose (HydroxypropylCellulose, Low-Substituted), Magnesium Aluminum Silicate, Maltose, Methylcellulose, Polacrilin Potassium), Pullulan, Colloidal Silicon Dioxide, Colloidal, Sodium Alginate, Sodium Starch Glycolate, Starch, Pregelatinized Modified, Corn Starch, Hydroxypropyl Corn Starch (Starch, Hydroxypropyl Corn), Pregelatinized Hydroxypropyl Corn (Starch, Pregelatinized Hydroxypropyl Corn), Pea Starch (Starch, Pea), Hydroxypropyl Pea Starch (Starch, Hydroxypropyl Pea), Pregelatinized Hydroxypropyl Pea Starch (Starch, Pregelatinized Hydroxypropyl Pea), Potato Starch (Starch, Potato), Hydroxypropyl Potato Starch (Star ch, Hydroxypropyl Potato), pregelatinized hydroxypropyl potato starch (Starch, Pregelatinized Hydroxypropyl Potato), tapioca starch (Starch, Tapioca), wheat starch (Starch, Wheat), etc., but is not limited thereto. The tablet of the present invention may not contain the components listed above as a disintegrant, but when the components are used as additives commonly used in the manufacture of tablets, such as excipients, lubricants, and binders, the above components are also of the present invention. may be included in tablets.

The “substantially free from disintegrant” includes including the disintegrant in the tablet in an amount smaller than the amount used for the disintegrant, usually for the purpose of improving the disintegration property of the tablet. In addition, the tablet of the present invention does not contain the disintegrant at all or may contain an amount that is not detected/measured through a conventional detection/measurement method.

The tablet of the present invention does not contain a disintegrant component commonly used at all or contains less than the amount of a conventional disintegrant, but can exhibit similar or superior disintegration quality to a tablet containing milk thistle extract using a disintegrant component. It has the advantage of being able to significantly increase the content of milk thistle extract, an active ingredient, while exhibiting sufficient disintegration properties.

The tablet of the present invention, through a test method according to the disintegration test method of the Korea Health Functional Foods Code, uses water at 35 ° C to 37 ° C as a solvent and an amplitude of 53 mm to 57 mm, and reciprocates up and down 29 to 32 times per minute. If the tablet does not remain in the test tube, or the material in the form of sponges, soft (soft) material, or The time required for dissolution (disintegration time) of the material remaining in the dough state may be 30 minutes or less or 60 minutes or less If the tablet is in the form of an uncoated tablet, the required time is 30 minutes or less, and the tablet In the case of a form coated with a coating agent (in the form of a coated tablet), the required time may be 60 minutes or less.

Specifically, the disintegration test is performed by the National Health Functional Foods Test Method (Specialized Test Method for Health Functional Food Standards and Specifications, 2021, Article 4. Health Functional Food Test Method, 2. General Test Method, 2-1 Disintegration Test Method) ), and water is used as a solvent so that the temperature of water is maintained at a temperature of 35 ° C to 39 ° C during the test, and 29 times per minute with an amplitude of 53 mm to 57 mm as a tester Using a tester that reciprocates up and down 32 times, put a tablet sample in water contained in a beaker, put an auxiliary plate, make the tester move up and down, and then check the state of the tablet.

When the tablet is an uncoated tablet, the disintegration time is 30 minutes or less, 25 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 9 minutes or less, 8 minutes or less, 7 minutes or less, 6 minutes or less, or 5 minutes or less can When the tablet is a coated tablet, the disintegration time is 60 minutes or less, 50 minutes or less, 40 minutes or less, 35 minutes or less, 30 minutes or less, 25 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 9 minutes or less , 8 minutes or less, 7 minutes or less, 6 minutes or less, or 5 minutes or less. The tablet of the present invention has a characteristic that the disintegration time is within the above range, and may exhibit disintegration quality of 'excellent level' or 'very excellent level' based on the disintegration quality evaluation criteria according to Table 2 below.

In a specific example of the present invention, the disintegration quality was measured through the disintegration test method as described above for tablets prepared including chicory extract and crystalline cellulose together with milk thistle extract. As a result, the time required for the tablets prepared by varying the contents of the chicory extract and the crystalline cellulose to disintegrate and reach a state determined to be dissolved is 34 minutes 10 seconds, 18 minutes 48 seconds, 14 minutes 6 seconds, and 4 minutes. It was measured in 34 seconds, indicating that all of them had excellent disintegration quality. In addition, the tablet of the present invention has a very short disintegration time of 4 minutes and 34 seconds, and while having excellent disintegration properties, it was possible to increase the content of the milk thistle extract used as an active ingredient to 52% by weight. It was confirmed that there is an advantage that the problem of disintegration reduction does not occur while including it.

The tablet of the present invention has a disintegration time measured after storage for 12 months or less, 9 months or less, 6 months or less, 3 months or less, 2 months or less, or 1 month or less after manufacture, 30 minutes or less, 25 minutes or less, 20 Minutes or less, 15 minutes or less, 10 minutes or less, 9 minutes or less, 8 minutes or less, 7 minutes or less, 6 minutes or less, or 5 minutes or less. The tablet of the present invention can exhibit excellent disintegration quality as the disintegration time is within the above range even after the above period has elapsed since manufacture.

The tablet of the present invention may further include additives such as diluents, binders, lubricants, stabilizers, film coating agents, plasticizers, and mixtures thereof.

The binder may be a silicate derivative such as hydroxypropylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, copovidone, macrogol, light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate or magnesium metasilicate aluminate; phosphates such as calcium hydrogen phosphate; carbonates such as calcium carbonate; It may be a mixture thereof, for example, hypromellose, polyvinylpyrrolidone, or a mixture thereof. The binder may be included in an amount of 1 to 5 parts by weight or 1 to 4 parts by weight based on 100 parts by weight of the total tablet.

The diluent is calcium carbonate, calcium phosphate, dextrin, dextrose, fructose, glyceryl palmitostearate, sucrose, lactose, glucose, mannitol, alkaline earth metal salts, clay, polyethylene glycol, dicalcium phosphate, mixtures thereof, etc. can

The lubricant may be talc, stearic acid and its salts, sodium lauryl sulfate, hydrogenated vegetable oil, sodium benzoate, sodium stearyl fumarate, glyceryl monostearate, polyethylene glycol, mixtures thereof, etc., for example, sodium stearyl fumarate can

The stabilizer may be butylated hydroxy toluene (BHT), butylated hydroxy anisole (BHA), ascorbic acid, tocopherol, edetic acid (EDTA), or mixtures thereof.

The film coating agent is gelatin, polyethylene glycol, shellac, polyvinyl alcohol, polyvinyl pyrrolidone, a polymer of vinyl pyrrolidone and vinyl acetate, ethyl acrylate methyl methacrylate methyl methacrylate trimethylammonium ethyl copolymer (eg, trade name) Eudragit RS or RL, Degusa), methyl methacrylate ethyl acrylate copolymer (eg, trade name Eudragit NE30D, Degusa), polyvinylacetyldimethylaminoacetate, mixtures thereof, etc. have.

The plasticizer may be glycol, ester, oil, glycerin, glycerin derivative, mixtures thereof, etc., among which glycol may be propylene glycol, polyethylene glycol, a mixture thereof, etc., and the ester is diethyl phthalate, dibutyl phthalate, dibutyl It may be sebacate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, triacetin, or mixtures thereof. The oil may be castor oil, coconut oil, mixtures thereof, and the like. Glycerin and glycerin derivatives may be glycerin, monostearic glycerin, mixtures thereof, and the like.

The tablet may further include a foaming agent, a buffer, a mixture thereof, and the like.

The foaming agent may be an inorganic material containing carbonate, an organic acid, etc., and the buffering agent is calcium carbonate, sodium dihydrogen phosphate, sodium monohydrogen phosphate, sodium glutamate, potassium citrate, sodium hydrogen carbonate, sodium citrate, sodium hydroxide, calcium phosphate, calcium hydrogen phosphate , or various salts, mixtures thereof, and the like.

2. Manufacturing method of tablets with improved disintegration

Another aspect of the present invention provides a method for preparing a tablet having improved disintegration.

The method for manufacturing the tablet of the present invention includes a step of mixing a milk thistle extract and a chicory extract.

The manufacturing method may further include; mixing a mixture of the milk thistle extract and chicory extract with crystalline cellulose to form granules.

The manufacturing method may further include; further adding crystalline cellulose to the granulated material for tableting.

The manufacturing method may further include; coating the compressed tablet with a coating agent.

The description of the tablets, milk thistle extract, chicory extract, crystalline cellulose, their content, characteristics, effects, etc. is described in '1. Since it is the same as that described in 'tablet with improved disintegration, description is omitted.

The step of forming the granules may be performed by a method such as dry granulation or wet granulation. Specifically, in the case of granulation with wet granules, first, a binder solution containing chicory extract is prepared, and a mixture of milk thistle extract, crystalline cellulose, etc. is mixed with the binder solution to form granules, then sieved and dried to obtain granules. Next, after adding and mixing crystalline cellulose and other ingredients, it can be tableted. When granulating with dry granulation, a mixture of milk thistle extract, chicory extract, crystalline cellulose, etc. is pressed and sieved using a roller compactor, etc. can do. In the case of direct compression without granulation, each component may be mixed and tableted immediately. However, direct tableting may not be possible if the fluidity of the milk thistle extract, the active ingredient, is not good.

In order to ensure the mixing uniformity of the tablet, when each component including the milk thistle extract is not added at the same time in the mixing step of the above ingredients, but dispersed in stages, the mixing uniformity of the mixture can be improved. For example, after adding and mixing a part of the crystalline cellulose and/or chicory extract to the milk thistle extract, a part of the crystalline cellulose and/or chicory extract is further added and mixed, and the remaining amount is added and mixed again, and finally A mixture for tableting may be prepared.

Since the capacity of the tablet may vary, it is also possible to set the shape, weight, and size of each 　 tablet 　 for each tablet, and then manufacture it with a punch of a suitable shape. The shape of the tablet may vary, such as rectangular, oval, diamond-shaped, circular, polygonal (eg, triangular, square, pentagonal, hexagonal, etc.). The shape of the tablet is related to the patient's convenience, ease of punch manufacturing and management, 　 tablet 　 ease of manufacturing such as tableting, coating, packaging and handling, whether the dissolution pattern can be adjusted, 　 hardness, friability, disintegration, etc. of the tablet It can be determined by comprehensively judging the ease of control of variables. In addition, it is possible to select and select a suitable shape according to each capacity.

The tableting may be performed using any tableting machine known to those skilled in the art. For example, the tableting may be performed with a compression force of 1 to 30 kN, 2 to 30 kN, 2 to 15 kN, or 3 to 15 kN. Alternatively, a so-called external lubrication and tableting method may be used by spraying or applying a lubricant such as magnesium stearate to a mortar or mortar of a tableting machine to lubricate it.

Hereinafter, the present invention will be described in detail by way of Examples.

However, the following examples specifically illustrate the present invention, and the content of the present invention is not limited by the following examples.

[Examples and Comparative Examples]

In order to prepare the tablet of the present invention with improved disintegration while using a poorly soluble active ingredient, milk thistle extract was used as an active ingredient, and chicory extract was added thereto to prepare a tablet. Crystalline cellulose used as a stabilizer, emulsifier, etc. in tablets was used together with the chicory extract, and by adjusting their ratio, Comparative Example 1-1, Comparative Example 1-2, and Examples 1-1 to Example 1- 4 tablets were prepared. The chicory extract was prepared through hot water extraction. The root of chicory was obtained, washed and cut, and then hot water at 80°C to 120°C was added to perform extraction. And the chicory extract was prepared and used through purification and evaporation through carbonation.

Specifically, a mixture for making tablets was prepared by mixing the powder of milk thistle extract, chicory extract, crystalline cellulose and stearic acid at a mixing ratio according to Table 1 below. First, milk thistle extract and crystalline cellulose were mixed. At this time, the amount of crystalline cellulose was mixed in an amount according to the item 'Crystalline cellulose (granules)' in Table 1 below. Here, chicory extract in an amount corresponding to about 8.0% to 9.5% of the weight of the milk thistle extract and crystalline cellulose mixture was dissolved in purified water to prepare a binder solution adjusted to a concentration of 15% to 30% to prepare granules. Then, a final mixture for tableting was prepared by further adding and mixing crystalline cellulose and stearic acid to the granules. The final mixture was tableted to be 500 mg per tablet using a tableting machine (GRC-15S, SEJONG PHARMATECH CO., LTD.) in Comparative Example 1-1, Comparative Example 1-2, and Examples 1-1 to 1 -4 tablets were prepared.

mixing ratio comparative example
1-1 comparative example
1-2 Example
1-1 Example
1-2 Example
1-3 Example
1-4 Milk Thistle Extract 68.421 65.000 61.176 57.778 54.737 52.000 chicory extract 7.895 7.500 7.059 6.667 6.316 6.000 Hydroxypropylmethylcellulose - - - - - - Crystalline Cellulose (Granule) 21.053 20.000 18.824 17.778 16.842 16.000 Crystalline cellulose (post-attached) - 4.500 9.941 14.778 19.105 23.000 stearic acid 2.632 3.000 3.000 3.000 3.000 3.000 Sum 100.000 100.000 100.000 100.000 100.000 100.000 Total amount of crystalline cellulose 21.053 24.5 28.765 32.556 35.947 39 Amount of chicory extract based on 100 parts by weight of the total amount of crystalline cellulose 37.50059 30.61224 24.54024 20.47856 17.57031 15.38462

[Experimental Example 1]

Using the tablets of Comparative Examples 1-1 and 1-2, and Examples 1-1 to 1-4, properties such as hardness and disintegrability were measured and compared.

The hardness of the tablet was measured using a hardness measuring instrument (TBH 425, ERWEKA), and the unit was Kp and shown in Table 3 below.

And in order to measure the disintegration properties of the tablets, their disintegration time was confirmed. Milk thistle used as the main ingredient of the tablet is a poorly soluble component that is difficult to dissolve in water due to the fat-soluble silymarin component contained therein. has a problem. The disintegration test is carried out according to the National Health Functional Foods Test Method (Special Test Method for Health Functional Food Standards and Specifications, 2021, Article 4. Health Functional Food Test Method, 2. General Test Method, 2-1 Disintegration Test Method) did Water was used as a solvent for dissolving the tablet, and the temperature of the water was maintained at a temperature of 35°C to 39°C during the test. As the tester, a tester that reciprocates up and down 29 to 32 times per minute with an amplitude of 53 mm to 57 mm was used, and the purified sample was put into water in a beaker, an auxiliary plate was put in, and the tester was moved up and down, and then the comparative example The state of the tablets of 1-1, 1-2 and Examples 1-1 to 1-4 was confirmed. According to the test method, when the sample is observed after performing vertical motion for 30 minutes, the residue of the purified sample is not in the glass tube, or even if it remains, it is in the form of a sponge. When there is a small amount of a substance, a soft substance, or a loin-like substance, it is judged that the disintegration property is suitable. And, according to the test method, it is judged to be suitable if the tablet is in the state described above within 30 minutes in the case of an uncoated tablet, within 60 minutes in the case of a tablet in the form of a coating (coated tablet) coated with a coating agent.

In this experimental example, an experiment was performed using the tester, and the time taken until a state suitable for the determination criterion was measured and compared. And the standards for disintegration quality are based on the standards according to Table 2 below to apply stricter standards than the standards according to the test method (disintegration time of uncoated tablets within 30 minutes, disintegration time of coated tablets within 60 minutes). Solubility was evaluated.

disintegration time score quality evaluation within 5 minutes 6 very good level 5-15 minutes 5 excellent level 15-30 minutes 4 30-40 minutes 3 average level 40-50 minutes 2 level of concern 50-60 minutes One level of concern more than 60 minutes 0 quality non-conforming

Table 3 shows the results of measuring various properties of the tablets of Comparative Examples 1-1 and 1-2 and Examples 1-1 to 1-4. The thickness and hardness of each tablet were all measured at similar levels, but there was a significant difference in disintegration time. The tablet of Comparative Example 1-1 took more than 80 minutes to reach a state determined to be disintegrated, and the tablet of Comparative Example 1-2 took 71 minutes and 9 seconds, so it was determined to be inappropriate. However, the tablets of Examples 1-1 to 1-4 were evaluated to have above average disintegration properties. In particular, in the case of the tablets of Examples 1-4, the time required for disintegration was measured to be very short (4 minutes and 34 seconds), and it was confirmed that the disintegration property was very excellent. It was confirmed that, despite the manufactured tablet, it has the characteristic of disintegrating at a fast rate.

Experiment result comparative example
1-1 comparative example
1-2 Example
1-1 Example
1-2 Example
1-3 Example
1-4 Thickness (mm) 5.91 5.82 5.85 5.89 5.98 5.98 Hardness (Kp) 14.45 16.47 16.025 14.956 15.547 14.067 disintegration time over 80 minutes 71 minutes and 9 seconds 34 minutes 10 seconds 18 minutes 48 seconds 14 minutes and 6 seconds 4 minutes and 34 seconds Disintegration quality evaluation 0 nonconforming 0 nonconforming 3 Moderate 4 Excellent 5 Excellent 6 very good

[Experimental Example 2]

Using the tablets of Examples 1-4, which showed the best disintegration in Experimental Example 1, the disintegration rate was compared with 8 commercially available tablets containing milk thistle extract. Commercially available products include Comparative Example 2-1 (Korea Ginseng Corporation, Hwanggancheon), Comparative Example 2-2 (Chong Kun Dang Health, Liver Health Super Care), Comparative Example 2-3 (Nutricore, Organic Milk Thistle), Comparative Example 2-4 (Palm Ntop, Milk Thistle Good for Liver), Comparative Example 2-5 (Esther Formula, ActiveHepacare Milk Thistle), Comparative Example 2-6 (GRN, All Night Milk Thistle 9 Plus), Comparative Examples 2-7 (Vanala, Milk Thistle) and Comparative Examples 2-8 (GNM, Natural Quality Healthy Liver Milk Thistle) were used. In addition, the appearance of the tablets of Examples 1-4 and Comparative Examples 2-1 to 2-8 was checked, and the tablets were placed in 100 ml of water at 37° C. and left for 1 minute, and then the shape of the tablets was confirmed. (Fig. 2). The disintegration test method and disintegration quality evaluation according to the measured disintegration time were the same as in Experimental Example 2, and the experimental results and information such as ingredients and contents of each tablet product are shown in Tables 4 and 5 below. In the case of products for which the content of the main ingredient is not indicated among commercially available products, it was calculated as expected based on the silymarin content in the milk thistle extract.

Example
1-4 comparative example
2-1 comparative example
2-2 comparative example
2-3 main raw material
(functional ingredients) Milk Thistle Extract Milk Thistle Extract Milk Thistle Extract Organic Milk Thistle Extract - Red Ginseng Powder Nicotinamide
zinc oxide
Vitamin B6 Hydrochloride
Vitamin B1 Hydrochloride
vitamin B2 - auxiliary material crystalline cellulose crystalline cellulose crystalline cellulose organic maltodextrin chicory extract - Lactose Mixed Powder organic glucose - Hydroxypropylmethylcellulose Hydroxypropylmethylcellulose Corn Protein Extract
powder stearic acid Magnesium Stearate Magnesium Stearate - - silicon dioxide silicon dioxide - - glycerin fatty acid ester glycerin fatty acid
ester - - Other concept raw materials Other concept raw materials - disintegrant - - - - Main ingredient content 52.00 18.572 43.33 (expected) 23.63636 daily intake 500mg/tablet×1 700mg/tablet×2=1400mg 600mg/tablet×1 1000mg/tablet×1 Date of Manufacture 2021.02.09 2019.07.05 2020.06.23 2021.01.14 disintegration time 4 minutes and 34 seconds 22 minutes and 8 seconds 49 minutes and 10 seconds 24 minutes 58 seconds disintegration quality 6 very good 4 Excellent 2 little concern 4 Excellent

comparative example
2-4 comparative example
2-5 comparative example
2-6 comparative example
2-7 comparative example
2-8 main raw material
(functional ingredients) Milk Thistle Extract Milk Thistle Extract Milk Thistle Extract Milk Thistle Extract Milk Thistle Extract dry yeast - dry yeast
Nicotinamide
zinc oxide
Calcium Pantothenate
Vitamin B6 Hydrochloride
Vitamin B1 Hydrochloride
vitamin B2
folic acid dry yeast
nicotinic acid amide
zinc oxide
Calcium Pantothenate
Vitamin B6 Hydrochloride
Vitamin B1 Hydrochloride
folic acid Nicotinamide
Calcium Pantothenate
Vitamin B6 Hydrochloride
Vitamin B1 Hydrochloride
vitamin B2 auxiliary material Chicory Extract Powder Lactose Mixed Powder crystalline cellulose crystalline cellulose crystalline cellulose seaweed powder crystalline cellulose - seaweed powder crystalline glucose - Hydroxypropylmethylcellulose hydroxypropyl
methylcellulose hydroxypropyl
methylcellulose hydroxypropyl
cellulose - Magnesium Stearate Magnesium Stearate Magnesium Stearate Magnesium Stearate - silicon dioxide silicon dioxide silicon dioxide silicon dioxide - glycerin fatty acid ester glycerin fatty acid
ester glycerin fatty acid
ester - Other concept raw materials - Other concept raw materials Other concept raw materials Other concept raw materials disintegrant corn starch Sodium crosslinked carboxymethylcellulose Carboxymethyl Cellulose Calcium Carboxymethyl Cellulose Calcium Carboxymethyl Cellulose Calcium Main ingredient content 16.25 (expected) 37.14 (expected) 28.89 (expected) 28.89 (expected) 28.89 (expected) daily intake 800mg/tablet×2=1600mg 700mg/tablet×1 900mg/tablet×1 900mg/tablet×1 900mg/tablet×1 Date of Manufacture 2020.12.23 2020.07.27 2020.11.26 2020.10.30 2020.12.15 disintegration time 16 minutes 48 seconds 30 seconds 1 min 6 minutes 55 seconds 25 minutes and 21 seconds disintegration quality 4 Excellent 6 very good 6 very good 5 Excellent 4 Excellent

As a result, in Comparative Examples 2-4 to 2-8 containing corn starch, cross-linked carboxymethyl cellulose sodium (croscarmellose sodium), and carboxymethyl cellulose calcium, which are disintegrant components for accelerating disintegration of tablets, disintegration It was confirmed that the quality was excellent or very good, and in the case of the tablets of Examples 1-4 of the present invention, the disintegration time was measured to be 4 minutes and 34 seconds, and disintegration properties similar to or superior to those of the tablets of the Comparative Example were shown. was able to confirm

However, in the case of the tablet of the present invention, the content of milk thistle extract, which is the main ingredient, reached 52%, which was significantly higher than that of other comparative examples. In the case of the products of Comparative Examples 2-4 to 2-8 using a disintegrant component, when the content of the milk thistle extract did not exceed 40% at most, the tablets of Examples 1-4 of the present invention had a longer disintegration time. Although it was short, it was confirmed that the content of the main raw material was remarkably high. On the other hand, in the case of the tablet of Comparative Example 2-2, the content of the main raw material was calculated as 43.33%, which was a high level, but the disintegration time was 49 minutes and 10 seconds, and it was confirmed that the disintegration property was poor, which was disintegrating despite containing crystalline cellulose. It could be expected that the effect of improving disintegration was improved by the chicory extract contained in the tablet of the present invention as this was not improved.

Therefore, even if the tablet of the present invention contains milk thistle extract, which is a poorly soluble component, as a main raw material, the disintegration time is significantly reduced, and similar or superior disintegration compared to products prepared by adding a conventional disintegrant. It showed degradability, and while having excellent disintegration properties, it could be confirmed that the main ingredient, milk thistle extract, could be included in a high content, thereby confirming that the daily intake was lower.

[Experimental Example 3]

Furthermore, it was confirmed whether the disintegration property was maintained without a change in disintegration quality according to the lapse of the storage period of the tablet of the present invention.

Specifically, the tablets of Examples 1-4 were divided into three groups under different temperature and relative humidity conditions and stored for 1 month, and then the disintegration quality was measured in the same manner as in Experimental Example 1. Storage conditions were 25 °C temperature and 60% relative humidity (RH), 35 °C temperature and 75% relative humidity, and 40 °C temperature and 75% relative humidity conditions for 1 month in Examples 1-4. The tablets were stored. The disintegration time, moisture content, hardness and thickness values of the tablets of the present invention according to each storage condition were measured and shown in Table 6 below.

Test Items Storage conditions 0 months 1 month 25℃, 60% RH 35℃, 75% RH 40℃, 75% RH disintegration time 4 minutes and 34 seconds 4 minutes 53 seconds 6 minutes 32 seconds 8 minutes 59 seconds disintegration quality 6 very good 6 very good 5 Excellent 5 Excellent moisture(%) 2.98 2.11 1.99 1.86 Hardness (Kp) 16.13±0.74 16.18±0.90 16.03±0.57 16.32±1.83 Thickness (mm) 6.01±0.02 6.03±0.03 6.03±0.03 6.03±0.01

As a result, under normal temperature and relative humidity conditions, the disintegration quality of the tablet did not change significantly even after 1 month had elapsed, so it was found to be very excellent, and the disintegration time after 1 month even when stored under elevated temperature and humidity conditions It appeared excellent in less than 10 minutes. Therefore, it was confirmed that the tablet of the present invention has an excellent effect of disintegration without deterioration in disintegration quality even after one month has elapsed.

In the above, the present invention has been described in detail only with respect to the described embodiments, but it is apparent to those skilled in the art that various changes and modifications are possible within the scope of the technical spirit of the present invention, and it is natural that such variations and modifications belong to the appended claims.

Claims (13)

milk thistle extract; chicory extract; and crystalline cellulose; as a tablet comprising:
Based on 100 parts by weight of the total tablet, the disintegration property is improved by including the milk thistle extract in an amount of 20 parts by weight or more and the chicory extract in an amount of 5 parts by weight to 7.2 parts by weight.
The method according to claim 1,
The tablet, wherein the milk thistle extract is included in an amount of 45 parts by weight or more based on 100 parts by weight of the total tablet.
delete The method according to claim 1,
The tablet, the tablet comprising the crystalline cellulose in an amount of 40 parts by weight to 80 parts by weight based on 100 parts by weight of the milk thistle extract.
The method according to claim 1,
The tablet, the tablet containing the crystalline cellulose in an amount of 25 parts by weight to 45 parts by weight based on 100 parts by weight of the total tablet.
The method according to claim 1,
The tablet does not contain a disintegrant, the tablet.
7. The method of claim 6,
The disintegrant is alginic acid (Alginic Acid), carboxymethylcellulose calcium (Carboxymethylcellulose Calcium), carboxymethylcellulose sodium (Carboxymethylcellulose Sodium), silicified crystalline cellulose (Cellulose, Silicified Microcrystalline), croscarmellose sodium (Croscarmellose Sodium), crospovidone (Crospovidone), Glycine, Guar Gum, Low-substituted HydroxypropylCellulose, Low-Substituted, Magnesium Aluminum Silicate, Maltose, Methylcellulose , Polacrilin Potassium, Pullulan, Silicon Dioxide, Colloidal, Sodium Alginate, Sodium Starch Glycolate, Gelatinized Modified Starch (Starch, Pregelatinized Modified), Corn Starch (Starch, Corn), Hydroxypropyl Corn Starch (Starch, Hydroxypropyl Corn), Pregelatinized Hydroxypropyl Corn (Starch, Pregelatinized Hydroxypropyl Corn), Pea Starch (Starch, Pea), Hydroxypropyl Pea Starch (Starch, Hydroxypropyl Pea), Pregelatinized Hydroxypropyl Pea (Starch), Potato Starch (Starch, Potato), Hydroxypropyl Potato Starch (Starch, Hydroxypropyl Potato) , Pregelatinized Hydroxypropyl Potato), Tapioca Starch (Starch, Tapioca) ) and wheat starch (Starch, Wheat) at least one selected from the group consisting of, the tablet.
The method according to claim 1,
Through the test method according to the disintegration test method of the Korean Health Functional Food Code, it is tested with a tester that reciprocates 29 to 32 times per minute with an amplitude of 53 mm to 57 mm using water at 35 ℃ to 39 ℃ as a solvent. , The tablet does not remain in the test tube, or the time it takes to dissolve as a spongy substance, a soft substance, or a louse-like substance is 30 minutes or less or 60 minutes or less, the tablet.
9. The method of claim 8,
When the tablet is in the form of an uncoated tablet, the required time is 30 minutes or less, and when the tablet is in the form of a coating agent, the required time is 60 minutes or less.
mixing milk thistle extract and chicory extract;
Forming granules by mixing the mixture and crystalline cellulose as a method of manufacturing a tablet comprising:
The tablet contains the milk thistle extract in an amount of 20 parts by weight or more, and the chicory extract is included in an amount of 5 parts by weight to 7.2 parts by weight, based on 100 parts by weight of the total tablet, the disintegration of the tablet is improved manufacturing method.
delete 11. The method of claim 10,
The method of manufacturing a tablet, further comprising a; further adding crystalline cellulose to the granulated material to be tableted.
13. The method of claim 12,
Coating the tableted tablet with a coating agent; further comprising, a method of manufacturing a tablet.

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