KR100857061B1 - Tablet containing vaccinium myrtillus extract and preparing method thereof - Google Patents

Abstract

A tablet containing the extract of Vaccinium myrtillus is provided to improve convenience and stability of package, delivery and storage. A preparation method of the Vaccinium myrtillus extract tablet is also provided to resolve the complication and difficulty of the conventional tablet preparation method. A stabilized Vaccinium myrtillus extract tablet contains 100-500mg of the extract of Vaccinium myrtillus, an excipient selected from microcrystalline cellulose and anhydrous lactose, and 5-30 mg of coating layer formed by one selected from hydroxypropylcellulose, hydroxypropylmethylcellulose, castor oil, propylene glycol, polyethylene glycol, povidone, talc, calcium carbonate, carnauba wax, silicon dioxide, metacrylic acid copolymer and titan oxide, wherein the mixing ratio by weight of Vaccinium myrtillus extract and microcrystalline cellulose or anhydrous lactose is 1:0.5 to 1:3 or 1:0.5 to 1:3.

Description

Tablet containing Bakinium Myrtilus extract and a method for preparing the same {TABLET CONTAINING VACCINIUM MYRTILLUS EXTRACT AND PREPARING METHOD THEREOF}

Figure 1a is a photograph showing the change in the appearance of the tablet according to the present invention after the accelerated test of the experimental example, 1b is a photograph showing the change in the appearance of the existing soft capsule after the accelerated test of Experimental Example 1.

Figure 2 is a graph comparing the content change according to the acceleration conditions of the experimental example of the formulation of the Example and the control example according to the present invention.

The present invention relates to a technique for formulating a Bakinium Myrtilus extract into a tablet (tablet), more specifically, to a predetermined excipient such as Bakynium Myrtilus extract, microcrystalline cellulose and / or anhydrous lactose It relates to a stable tablet containing and a method for producing the same.

Fruits from plants such as Vaccinium myrtillus , Ribes nigrum , Vitis vinifera , and Sambucus nigra , treat damaged microcirculation and shortsighted And starting materials for the preparation of anthocanoside-containing extracts widely used in the ophthalmic field for the treatment of eye fatigue.

In general, the anthocyanide component activates the synthesis of rhodopsin, a visually related substance in the human retina, inhibits various enzymes that are harmful to visual function, and results in the capture of free radicals of free radicals. It is known to be effective in improving vision and improving night blindness. Therefore, a method of extracting an anthocyanide component from blueberries and the like and various visual acuity improving agents commercialized using such a manufacturing method are introduced.

In particular, the bilberry (bilberry) is a medicinal plant widely used in Europe, the Bakinium myrtilus is extracted from the myrtle juice belonging to the bilberry. During World War II, British aviation pilots made jams from blueberries, the fruit of myrtle, to relieve eye strain and improve vision before nighttime operations. At this time, there were reports that pilots had better night blindness and better vision than usual (Alternative Medicine Review 5: 164-73, 2000). With this in mind, the French Cifres Institute found an active ingredient anthocyanin in myrtle, studied its pharmacological action, and successfully formulated it into bakinium myrtileusx.

The mechanisms by which anthocyanides affect eye health, such as improved vision and night blindness, are not fully understood, but academia suggests that they help regenerate rhodopsin, a photosensitive pigment (Social Biology Clermont-Ferrand 160: 1590- 3, 1966), regulating enzymatic activity in the retina (Review of Medicine Aeronautique et Spatiale 18: 45-50, 1966) and suggesting that it improves microcirculation (Alternative Medicine Review 5: 164-73, 2000 ).

In Europe and North America, such as Canada and the United Kingdom, bilberry extract is widely used as a nutritional supplement, and some pharmaceutical companies sell bilberry extract in combination with ingredients such as vitamins and lutein. Representative examples include Tobicom of Anguk Pharm, Memobis of Yeongil Pharm, and Tagen F of International Pharm.

Most of the formulations for oral administration containing such bachynium myrtilus extract are sold in the form of soft capsules, and are sold in the form of tablets only when added in small amounts, and there are no examples of tablet formulations. This is because the barkinium myrtilus extract is well moisturized to form spots on the surface of the tablet, and if the content in the tablet is high, it is difficult to formulate it into tablets due to the difficulty in tableting due to the large amount of powder during the manufacturing process. to be. However, when formulated as a soft capsule, the above discomfort is reduced, but the addition of an additional preservative, separation of the coating and the contents in the change over time, sticking in the summer use, causing gastrointestinal disorders caused by gelatin, cost increase Many problems arise.

Therefore, in order to solve the problems of the soft capsule as described above, there is a demand for the development of a technique for formulating the Bakynium Myrtilus extract into a stable tablet.

Accordingly, the present invention solves the problems of the soft capsules as described above, overcomes the technical difficulties that are problematic in the formulation into tablets, tablets containing a bakinium myrtilus extract stable over time change and a method for producing the same The purpose is to provide.

The present invention relates to a technique for formulating a Bakinium Myrtilus extract into a tablet, more specifically, a stable tablet containing Bakinium Myrtilus extract, microcrystalline cellulose and / or anhydrous lactose, and It relates to a production method thereof.

 Bakinium Myrtilus extract is present as a powder and contains a dark purple pigment, which contaminates the surroundings during the manufacturing process, and is sensitive to heat and moisture, and is not manufactured as a tablet and is mostly formulated in the form of soft capsules. It is commercially available. However, as described above, when formulated as a soft capsule, the stability of the contained Bakinium Myrtilus extract rapidly decreases with time and heat changes, such as heat and moisture, there is an inconvenience that the capsules stick to each other when taking in summer In addition, there is a possibility that the gelatin component of the soft capsule may cause gastrointestinal disorders. In addition, the oil component in the soft capsule is easy to cure in a high temperature and / or a humid environment, such as during long-term storage or in the summer, it will delay the time the active ingredient contained in the body disintegrates, thereby reducing the absorption rate of the active ingredient in the body It is expected to drop.

The present invention is to formulate the Bakinium Myrtilus extract into a tablet, to solve the problems of the soft capsule as described above, and to overcome the drawbacks in the manufacturing process and soft capsule formulation that can occur due to the presence of a large amount of powder. It is characterized by a formulation technology of tablets that can not only improve packaging, distribution and storage, but also can improve the stability of the formulation by forming an appropriate coating layer on the surface.

In the case of producing tablets according to the present invention, it is possible to reduce the cost incurred in the production of soft capsules, and instead of PTP (Polyol Templating and Partitioning) packaging used in the packaging of soft capsules, the virtue of packaging can be reduced and the dosage is reduced. This has the advantage of being convenient.

Typically, in the manufacture of tablets, when the main component is present in a powder of 20 to 30% by weight or more, most of the wet granulation process, but if it is less than orthogonal method is used a lot to reduce the inconvenience of the manufacturing process. However, when the powder occupies 20 to 30% by weight or more in the tablet weight, it is difficult to tablet by direct hitting method, especially when the main ingredient is a natural product, there is a difficulty in using a solvent in the granulation process because it is weak in moisture.

Thus, in the present invention, in the tabletting to include more than 20 to 30% by weight of the main ingredient of barium militia extract, by controlling the content of the active barium militia extract and excipients appropriately, the existing bakinium mir It is characterized by eliminating the process complexity and difficulty that occurred when formulating the tylus extract into a tablet. In addition, in the present invention, in order to improve the instability of heat and moisture of the uncoated Bakinium myrtilus extract is coated with an appropriate coating material to prepare a tablet stable even over time changes over time.

Bakinium myrtilus extract used in the present invention is an alcohol having 1 to 5 carbon atoms, preferably ethanol extract obtained from dry seeds of Vaccinium myrtillus , 33% of anthocanoside (Anthocyanoside) It means containing more. In one embodiment of the present invention, the Bakinium Myrtilus extract takes 100 kg of dried seeds (Bilberry Fruit. Dried, EP) of Vaccinium myrtillus , add 70% ethanol (KP), 25 It may be about 0.5 to 1.0 kg of powder obtained by extraction for 5 to 10 hours at -45 ℃, and the obtained extract is concentrated, purified, filtered and dried and then ground.

The tableting technique of the present invention is divided into tableting by direct powder compression method after mixing all active ingredients and excipients, and mixing and tableting active ingredients after wet granulation of components other than the active ingredient. In case of using direct powder compression method, the manufacturing process time is shortened by half, and there is an advantage of reducing the contamination problem of working environment due to pigment due to the nature of the active ingredient. The advantage is that the tablet size can be reduced.

First, the present invention is 100mg to 500mg, more preferably 100mg to 300mg extract of barium militia extract as an active ingredient; At least one excipient selected from the group consisting of microcrystalline cellulose and anhydrous lactose; And a stabilized bakinium myrtilus extract containing tablet containing 5 mg to 30 mg of the coating layer.

In another aspect, the invention

Mixing 100 mg to 500 mg, more preferably 100 mg to 300 mg, with at least one excipient selected from the group consisting of microcrystalline cellulose and anhydrous lactose;

Tableting the mixture to produce uncoated tablets; And

Forming a coating layer of 5mg to 30mg on the uncoated surface

It provides a method for producing a stabilized tablet containing Bakinium Myrtilus extract comprising. The tableting method may be by a direct powder compression method (direct stroke method).

As the excipient, microcrystalline cellulose or anhydrous lactose or both thereof may be used, and the microcrystalline cellulose and anhydrous lactose used herein may have an average particle size of 100 to 300 μm. If the average particle size of microcrystalline cellulose and anhydrous lactose is smaller than the above range, capping and peeling phenomenon occur during tableting, and the tableting is difficult due to poor fluidity. As a result, there is a problem of variation in content uniformity due to this), so that the average particle size of the microcrystalline cellulose and the anhydrous lactose is preferably within the above range.

As noted above, in order to formulate the Bakinium Myrtilus extract into a stabilized tablet, the mixing ratio of the Bakinium Myrtilus extract with microcrystalline cellulose and / or anhydrous lactose used as excipient is important. In order to achieve the object of the present invention, the mixing ratio of the bakinium myrtilus extract and the microcrystalline cellulose is 1: 0.5 to 1: 3 (weight of the barkium myrtilus extract: microcrystalline cellulose weight) by weight In addition, the mixing ratio of the bakinium myrtilus extract and anhydrous lactose is preferably 1: 0.5 to 1: 3 (barkium myrtilus extract weight: anhydrous lactose weight) based on the weight. When both microcrystalline cellulose and anhydrous lactose are used as excipients, the mixing ratio of the barchinium myrtilus extract, microcrystalline cellulose and anhydrous lactose is 1: 0.5 to 3: 0.5 to 3, preferably 1: 0.7 to 3: 0.7 to 3, more preferably 1: 1 to 3: 1 to 3 (Bakinium Myrtilus extract weight: microcrystalline cellulose weight: anhydrous lactose weight). When the content of the excipient is less than the above range, there is a problem in that the compression molding itself is difficult due to the presence of a large amount of active ingredient powder, and in the case of more than the above range, the tablet size becomes too large to be difficult for the elderly or children to take. , The content of the excipient is preferably in the above range.

In a preferred embodiment of the present invention, the tablet may contain about 100 to 500 mg of Bakinium Myrtilus extract, about 100 to 300 mg of microcrystalline cellulose and about 50 to 350 mg of anhydrous lactose.

In addition to the active ingredient and excipient, the tablet of the present invention may further contain one or more selected from the group consisting of conventional disintegrants, additional conventional excipients, and conventional lubricants.

At this time, the disintegrant may be one or more selected from the group consisting of crospovidone, sodium starch glycolate, gelatinized starch, corn starch, carboxymethyl cellulose and microcrystalline cellulose. The disintegrant is to disintegrate after administration into the body to release the active ingredient, if the content is excessively disintegrated proceeds too fast to increase the initial release of the active ingredient is difficult to obtain a continuous effect, if the content is too small Since the disintegration is excessively delayed and the release rate of the active ingredient is slowed, so that it is difficult to obtain an effective effect quickly, it is preferably contained in an amount of 3 to 20 parts by weight based on 100 parts by weight of the active ingredient. The additional excipient is to aid in the formulation into tablets, and may be one or more selected from the group consisting of lactose, propylene glycol, sodium hydrogen carbonate, magnesium carbonate, methacrylic acid copolymer, and calcium hydrogen phosphate anhydride. If the content is too small, the effect is insignificant, and if the content is too high, it affects the activity of the active ingredient. Therefore, it is preferably contained in an amount of 50 to 500 parts by weight based on 100 parts by weight of the active ingredient. In addition, the lubricant is to provide fluidity to the tablets to play a role to easily come off the tablet, silicon dioxide, light anhydrous silicic acid, magnesium stearate, talc, and at least one selected from the group consisting of synthetic aluminum silicate It may be, and preferably contained in an amount of 2 to 10 parts by weight based on 100 parts by weight of the active ingredient.

Since the barkynium myrtilus extract in the uncoated state is unstable to heat and moisture, the tablet containing the bakinium myrtilus extract of the present invention includes a coating layer formed from an appropriate coating material, thereby maintaining stability over time. The coating material may be any tablet coating material commonly used, such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, castor oil, propylene glycol, polyethylene glycol, povidone, talc, calcium carbonate, carnauba wax, dioxide Silicon, methacrylic acid copolymer (eg, Eudragit RL, Eudragit RS, Eudragit S, Eudragit E30D, Eudragit L30D, etc.) and titanium oxide, and at least one member selected from the group consisting of It may further contain a coloring agent such as Opadry (Colorcon).

The coating layer of the present invention can be formed by applying the suspension or dispersion obtained by mixing the coating material in an organic solvent to the uncoated surface, the content of the coating layer in the tablet containing 100 to 500 mg of the active ingredient after removal of the organic solvent 5 mg to 50 mg is preferred based on the weight of solids. When the coating layer content is less than the above range, the stability of the tablet cannot be sufficiently secured, and when the coating layer content is more than the above range, it prevents proper disintegration of the tablet and effective release of the active ingredient, so the content of the coating layer is preferably within the above range.

The coating layer formation in the tablet of the present invention is sprayed onto a bed on which the tablet rotates while spraying a suspension or dispersion in which the coating material is dispersed in an organic solvent through a nebulizer nozzle or passing hot air to remove the solvent. It may be carried out by a conventional method such as. At this time, the spraying speed is the speed used in the usual coating, it is good that the tablets do not stick to each other. In addition, the organic solvent is a component that is dried and removed after the coating layer is formed, and may be all organic solvents commonly used in the manufacture of tablets, for example, in the group consisting of water, alcohol having 1 to 5 carbon atoms, methylene chloride, and acetone. It may be one or more selected.

In another aspect, the present invention is the active ingredient in the group consisting of 100 mg to 500 mg, preferably 100 mg to 300 mg, one or more disintegrants, one or more excipients and one or more lubricants. Provided are wet granules containing at least one selected, and tablets containing a stabilized Bakinium Myrtilus extract containing 5 mg to 30 mg of a coating layer.

The tablet containing barchinium myrtilus extract of the present invention may further contain a suitable additive depending on the intended use. The extract may be at least one selected from the group consisting of ascorbic acid, alpha tocopheryl acetate, lutein, zeaxanthin, alpha-lipoic acid, zinc, copper, ginkgo biloba extract, and green tea extract. It can be suitably adjusted in the range of 1 to 1000 parts by weight, preferably 10 to 800 parts by weight based on 100 parts by weight of the tylus extract.

In another aspect, the invention

Mixing at least one selected from the group consisting of at least one disintegrant, at least one excipient, and at least one lubricant, and wet granulating the resulting mixture to produce wet granules;

Preparing a uncoated tablet by mixing the wet granules with 100 mg to 500 mg, preferably 100 mg to 300 mg, of barchinium myrtilus extract; And

Forming a coating layer of 5mg to 30mg on the obtained uncoated surface

It provides a method for producing a stabilized tablet containing Bakinium Myrtilus extract comprising.

The wet granules are

At least one disintegrant selected from the group consisting of crospovidone, sodium starch glycolate, gelatinized starch, corn starch, carboxymethyl cellulose and microcrystalline cellulose;

At least one excipient selected from the group consisting of microcrystalline cellulose, anhydrous lactose, lactose, propyleneglycol, sodium hydrogencarbonate, magnesium carbonate, methacrylic acid copolymer, and anhydrous calcium hydrogen phosphate; And

At least one lubricant selected from the group consisting of silicon dioxide, light silicic anhydride, magnesium stearate, talc, and synthetic aluminum silicate

After mixing at least one selected from the group consisting of an organic solvent, it may be granulated by a conventional method.

The content of the wet granules in the tablet of the present invention may be 50 to 500% by weight, preferably 100 to 300% by weight, based on 100 parts by weight of the extract of the active ingredient, bakinium myrtilus. If the amount of the wet granules in the tablet is larger than the above range, the size of the tablet becomes larger, which makes the feeling of taking uncomfortable, the production efficiency worsens, and if it is less than the above range, the amount of powder to the weight of the whole tablet increases, making it difficult to receive compression pressure. Since tableting becomes difficult and there is a problem that it becomes difficult to control physical properties such as disintegration, wear and tear, and hardness of tablets, the content of the wet granules is preferably within the above range. The wet granules are the content of disintegrants, excipients and lubricants in the above. That is, the wet granules may contain 3 to 20 parts by weight of disintegrant, 45 to 500 parts by weight of excipient, and 2 to 10 parts by weight of lubricant based on 100 parts by weight of the active ingredient.

Granulation of the wet granules can be carried out directly without the use of binders or by means of suitable binders. The binder is at least one selected from the group consisting of povidone, low-substituted propyl cellulose (degree of substitution 7 to 10%), gelatinized starch, polyvinyl alcohol, corn starch, gelatin, sodium sodium starch glycol, lactose, and cellulose It may be a wet bonding material, and for the preparation of wet granules suitable for the present invention, it is preferable to use the amount in an amount of 0.0001 to 0.1 parts by weight based on 100 parts by weight of the active ingredient.

The organic solvent used in the manufacture of wet granules is a component which is dried and removed after granule formation, and may be all organic solvents commonly used in wet granulation processes, for example, water, alcohol having 1 to 5 carbon atoms, methylene chloride, and It may be one or more selected from the group consisting of acetone.

The coating material and the coating layer forming process for forming the coating layer are as described above.

In addition, the tablet may further include a suitable additive according to the purpose of use, the kind and content thereof are as described above.

Tablets according to the invention can be conveniently stored for a long time in a suitable container. The container is preferably sealed to prevent the penetration of water, and it is better to put a desiccant in the container.

Hereinafter, the present invention will be described in more detail with reference to the following examples. But. These examples are merely illustrative of the present invention, and the scope of the present invention is not limited by these examples.

EXAMPLE

Examples 1 to 9 Preparation of Tablets by Direct Powder Compression

The components shown in Table 1 below were passed through a 28 mesh sieve, mixed, and then compressed and compressed in a tablet press (KT-3733, Venus). The number of the uncoated tablets obtained was about 5000 pieces. The components and contents contained in the refined sugars are shown in Table 1 below. The unit of the numerical value of Table 1 is mg.

TABLE 1

Comparative Examples 1 to 4

The ingredients shown in Table 2 below were passed through a 28 mesh sieve, mixed, and then compressed and compressed in a tablet press (KT-3733, Venus). The number of the uncoated tablets obtained was about 5000 pieces. The components and contents contained in the refined sugars are shown in Table 2 below. The unit of the numerical value of Table 1 is mg.

TABLE 2

Experimental Example 1 Measurement of Hardness and Disintegration Time of Tablets

The hardness and disintegration time of the tablets prepared in Examples 1 to 9 and Comparative Examples 1 and 3 were measured.

Hardness was measured by the Pharmatest test system (PTB4112), the average of the ten was measured. The disintegration time was measured by using a disintegrating machine (ERWEKA ZT-504) and six tablets were tested according to the disintegration test method of the Pharmacopoeia 8 general test method to obtain an average value. The hardness and disintegration time thus obtained are shown in Table 3 below.

TABLE 3

As can be seen in Table 3, the tablets of the present invention (Examples 1 to 9) have a hardness of 8 ~ 10Kp, considering that the hardness required for coating is at least 7kP or more, there is no difficulty in coating work at all. The hardness was shown, and rapid disintegration within 15 minutes is expected to increase the absorption rate in the body. On the other hand, in the comparative example, the hardness of the tablet was 4 to 5 kP, and the wear phenomenon occurred, and when measuring the wear and tear of the tablet, the capping or peeling of about 4 to 5 was generated when measuring 20 tablets.

Example 10 Preparation of Tablets Through Wet Granules Preparation

10-1: Preparation of Wet Granules

Povidone K30 was dissolved in 60% ethanol and then thoroughly mixed by adding anhydrous lactose, microcrystalline cellulose and crospovidone. The povidone K30 was used as binder and the mixture was granulated for 20 minutes. The obtained granules were passed twice through 14 meshes, and then dried in a drier at 40 ° C. until the moisture content was 3% by weight or less to obtain wet granules.

The ingredients and contents used per tablet in this example are as follows:

Povidone K30 (BASF) 10 mg

500 mL of 60% ethanol

Anhydrous lactose (DMV, DCL21) 140 mg

Microcrystalline Cellulose (JRS PHARMA, VIVAPUR200) 100 mg

Crospovidone (BASF) 5 mg

10-2: Preparation of Tablet

To the wet granules prepared in Example 10-1, the following components were mixed and stirred for 20 minutes with the following contents, and the resulting mixture was compressed in a rotary compressor (KT-3733, Venus) to prepare uncoated tablets.

In the present embodiment, the components and contents contained per tablet are as follows:

255 mg of granules of Example 10-1

Bachinium Myristicus (Linnea) 170 mg

Crospovidone (BASF) 5 mg

Magnesium Stearate (NOF) 5 mg

Example 11: Coating of Tablets

Tablets (coated tablets) prepared in Examples 1 to 10 were film-coated with a coating material of the following components.

The composition and content of the coating material used per tablet is as follows:

Hydroxypropylmethylcellulose 2910 (Shin Etus) 16 mg

Polyethylene glycol 6000 (SanYo) 303 mg

Titanium Oxide (KRONOS) 0.6 mg

Talc (Duksan Chemical) 0.93 mg

The coating material was added to a mixed solvent of methylene chloride and ethanol (methylene chloride: ethanol: water = 3: 1: 1, 80%) and the coating material was dispersed and dissolved using a homomixer. The fine suspension obtained was sprayed onto a bed with tablets rotating while passing hot air to remove solvent through the atomizer nozzle (No. 3, Samhwa Korea). The spray rate was the rate used for normal coating, and the rate at which the tablets did not stick together.

Experimental Example 2: Stability at Time Change of Tablet

100 tablets of the coated tablets (hereinafter referred to as "tablets of Example 1") prepared according to Examples 1 and 11 were placed in a polyethylene bottle, silica gel (1 g) was added thereto, and the stopper was closed. It was. At this time, the tablets of Example 1 and the soft capsule of the main component content as a control example. In the case of the soft capsule, the stability test was carried out in a commercially packaged PTP packaging.

The soft capsule used as the control was prepared as follows:

1) Composition: In soft capsule

(chief ingredient)

Bakinium Myristicus ----------- 170mg

(Excipient)

Soybean oil ------------------------- 230mg

Hard Fat ------------------------ 42.0mg

Saccharin -------------------------- 14.0mg

Lecithin ----------------------- 10.0mg

(Soft capsule base)

Succinate Gelatin ------------------- 123.9 mg

Concentrated glycerin --------------------- 55.8mg

Sorbitol solution (70%) ----------------- 19.5mg

(Preservative)

Paraoxybenzoic Acid Methyl ----------- 0.30 mg

Paraoxybenzoate --------- 0.07mg

In addition, air fresheners, colorants, light-shielding agents, etc.

2) manufacturing

For the comparative experiment, 5000 capsules were commissioned by R.P.Scherer, a consignment producer.

The test equipment and test conditions used in this test are as follows:

Test equipment

Thermo-hygrostat, UV-Spectrophotometer-Measurement wavelength540nm

Exam conditions

Room temperature storage condition: 25 ℃, 60% RH

Accelerated storage conditions: 40 ℃, 75% RH

After 2 months of accelerated storage, changes in the properties of the tablets of Example 1 and the control examples (soft capsules) are shown in FIGS. 1A and 1B. As can be seen in Figures 1a and 1b, the tablet of Example 1 shown in Figure 1a, even after 2 months of accelerated storage under the above conditions and no change was observed, the soft capsule shown in Figure 1b is an oil layer And contents were separated, and contents were observed to cure and harden.

Changes in the anthocyanoid content in the Bakinium Myrtilus extract during accelerated storage and room temperature storage were measured and shown in Tables 4 and 5, and FIG. 2, respectively.

[Table 4] Content change in accelerated storage

 Elapsed date Example 1 Control Initial 1 month 3 months 6 months 100.6% 101.0% 100.2% 97.4% 100.8% 77.9% 36.2% 16.4%

TABLE 5 Changes in content at room temperature

 Elapsed date Example 1 Control Initial 1 month 3 months 6 months 100.6% 101.0% 102.8% 100.8% 100.8% 97.4% 96.0% 82.6%

As shown in the results of Table 4, Table 5 and Figure 2, the tablets of Example 1 according to the present invention showed significantly superior stability at room temperature and accelerated storage than the control formulation formulated with commercially available soft capsules.

In the present invention, a tablet containing a large amount of extract of the barchinium myrtilus, by appropriately adjusting the content of the active ingredient and the excipients of the barkium myrtilus extract, when formulating the conventional barkinium myrtilus extract into a tablet Eliminating the process complexity and difficulty that occurred, and improved the convenience and stability of tablet packaging, distribution and storage.

Claims (18)

100 mg to 500 mg of Bakinium Myrtilus extract as active ingredient; At least one excipient selected from the group consisting of microcrystalline cellulose and anhydrous lactose; And 5 mg to 30 mg of the coating layer, The mixing ratio of the Bakinium Myrtilus extract and the microcrystalline cellulose is 1: 0.5 to 1: 3 (Bakinium Myrtilus extract weight: microcrystalline cellulose weight), The mixing ratio of the Bakinium Myrtilus extract and anhydrous lactose is 1: 0.5 to 1: 3 (Bakinium Myrtilus extract weight: weight of anhydrous lactose), Tablet containing stabilized Bakinium Myrtilus extract. The method of claim 1, The excipient includes both microcrystalline cellulose and anhydrous lactose, Tablets in which the mixing ratio of the bakinium myrtilus extract, microcrystalline cellulose and anhydrous lactose is 1: 0.7 to 3: 0.7 to 3 (barkium myrtilus extract weight: microcrystalline cellulose weight: anhydrous lactose weight) by weight . The method of claim 1, The microcrystalline cellulose has an average particle size of 150 to 300 μm, and the anhydrous lactose has an average particle size of 100 to 300 μm. The method of claim 1, The coating layer is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, castor oil, propylene glycol, polyethylene glycol, povidone, talc, calcium carbonate, carnauba lead, silicon dioxide, methacrylic acid copolymer, and titanium oxide What is formed from one or more tablets. The method of claim 1, At least one disintegrant selected from the group consisting of crospovidone, sodium starch glycolate, gelatinized starch, corn starch, carboxymethyl cellulose and microcrystalline cellulose; At least one additional excipient selected from the group consisting of lactose, propyleneglycol, sodium hydrogen carbonate, magnesium carbonate, methacrylic acid copolymer, and anhydrous calcium hydrogen phosphate; And At least one lubricant selected from the group consisting of silicon dioxide, light silicic anhydride, magnesium stearate, talc, and synthetic aluminum silicate Tablets further containing. The method of claim 1, A tablet further containing at least one additive selected from the group consisting of ascorbic acid, alpha tocopheryl acetate, lutein, zeaxanthin, alpha-lipoic acid, zinc, copper, ginkgo biloba extract, and green tea extract. Mixing 100 mg to 500 mg of bakinium myrtilus extract with at least one excipient selected from the group consisting of microcrystalline cellulose and anhydrous lactose; Tableting the mixture to produce uncoated tablets; And Forming a coating layer of 5mg to 30mg on the uncoated surface Including, The mixing ratio of the Bakinium Myrtilus extract and the microcrystalline cellulose is 1: 0.5 to 1: 3 (Bakinium Myrtilus Extract weight: microcrystalline cellulose weight), The mixing ratio of the Bakinium Myrtilus extract and anhydrous lactose is 1: 0.5 to 1: 3 (Bakinium Myrtilus extract weight: anhydrous lactose weight), Method for preparing a tablet containing stabilized Bakinium Myrtilus extract. The method of claim 7, wherein As the excipient, both microcrystalline cellulose and anhydrous lactose are included, The mixing ratio of the bakinium myrtilus extract, microcrystalline cellulose and anhydrous lactose is 1: 0.7 to 2: 0.7 to 2 (barkium myrtilus extract weight: microcrystalline cellulose weight: anhydrous lactose weight) based on weight. Way. The method of claim 7, wherein The microcrystalline cellulose has an average particle size of 150 to 300 μm, and the anhydrous lactose has an average particle size of 100 to 300 μm. The method of claim 7, wherein The coating layer is formed of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, castor oil, propylene glycol, polyethylene glycol, povidone, talc, calcium carbonate, carnauba wax, silicon dioxide, methacrylic acid copolymer, and titanium oxide It is carried out using a suspension in which at least one selected from among dissolved in an organic solvent. The method of claim 7, wherein The tableting step is performed by a direct powder compression method. 100 mg to 500 mg of Bakinium Myrtilus extract as active ingredient; Wet granules; And 5 mg to 30 mg of the coating layer, The wet granules are one or more disintegrants selected from the group consisting of crospovidone, sodium starch glycolate, gelatinized starch, corn starch, carboxymethyl cellulose and microcrystalline cellulose, microcrystalline cellulose, lactose anhydrous, lactose, At least one excipient selected from the group consisting of propylene glycol, sodium hydrogen carbonate, magnesium carbonate, methacrylic acid copolymer, and calcium hydrogen phosphate anhydrous, and silicon dioxide, light anhydrous silicic acid, magnesium stearate, talc, and synthetic aluminum silicate It contains at least one lubricant selected from the group, The content of the wet granules is 50 to 500 parts by weight based on 100 parts by weight of the active ingredient, Tablet containing stabilized Bakinium Myrtilus extract. The method of claim 12, The wet granules comprise at least one wet binder material selected from the group consisting of povidone, low-substituted propyl cellulose, gelatinized starch, polyvinyl alcohol, corn starch, gelatin, sodium starch glycolate, lactose, and cellulose. The tablet further comprises in an amount of 0.0001 to 0.1 parts by weight based on 100 parts by weight. The method of claim 12, The coating layer is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, castor oil, propylene glycol, polyethylene glycol, povidone, talc, calcium carbonate, carnauba lead, silicon dioxide, methacrylic acid copolymer, and titanium oxide A tablet formed from one or more. The method of claim 12, A tablet further containing at least one additive selected from the group consisting of ascorbic acid, alpha tocopheryl acetate, lutein, zeaxanthin, alpha-lipoic acid, zinc, copper, ginkgo biloba extract and green tea extract. 1 or more disintegrants selected from the group consisting of crospovidone, sodium starch glycolate, gelatinized starch, corn starch, carboxymethyl cellulose and microcrystalline cellulose, microcrystalline cellulose, lactose anhydrous, lactose, propylene glycol, carbonic acid At least one excipient selected from the group consisting of sodium hydrogen, magnesium carbonate, methacrylic acid copolymer, and anhydrous calcium hydrogen phosphate, and at least one selected from the group consisting of silicon dioxide, light anhydrous silicic acid, magnesium stearate, talc, and synthetic aluminum silicate Mixing the above lubricants and wet granulating the obtained mixture to prepare wet granules; Preparing a uncoated tablet by mixing the wet granules with 100 mg to 500 mg of barkinium myrtilus extract; And Forming a coating layer of 5mg to 30mg on the obtained uncoated surface Including, The mixing ratio of the bakinium myrtilus extract and the wet granules is 50 to 500 parts by weight of the wet granules with respect to 100 parts by weight of the bakinium myrtilus extract, Method for preparing a tablet containing stabilized Bakinium Myrtilus extract. The method of claim 16, Preparation of the wet granules comprises at least one wet binder material selected from the group consisting of povidone, low-substituted propyl cellulose, gelatinized starch, polyvinyl alcohol, corn starch, gelatin, sodium starch glycolate, lactose, and cellulose. The method is carried out using the amount of 0.0001 to 0.1 parts by weight based on 100 parts by weight of the Bakinium Myrtilus extract. The method of claim 16, The coating layer is formed of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, castor oil, propylene glycol, polyethylene glycol, povidone, talc, calcium carbonate, carnauba wax, silicon dioxide, methacrylic acid copolymer, and titanium oxide It is carried out using a dispersion mixture of at least one selected from organic solvents.

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