KR101581347B1 - Solid oral formulation comprising viscous extract of Magnolia cortex - Google Patents

Abstract

The present invention relates to a solid preparation for oral administration containing supersaturated soft X-ray and a preparation method thereof. The present invention can be manufactured without any manufacturing difficulties and is industrially useful when it is formulated into a general manufacturing facility, and it can be produced without difficulty in manufacturing, The present invention provides a solid preparation for oral administration containing an extended-release soft X-ray enhanced in storage stability without causing a change.

Description

[0001] The present invention relates to a solid oral preparation containing a viscous extract of Magnolia cortex,

The present invention relates to a solid preparation for oral administration containing a deep-fried soft-drink extract and a process for producing the solid preparation.

Magnolia cortex contains Magnolia obovata Thunberg, Magnolia officinale Rehder et Wils, and Machilus thunbergii Sieb. Et Zucc, which belong to Magnoliaceae. As a perennial herb, it is known to have the efficacy of a hunching (行 气 燥濕) and an anti-pyeongcheon (逆 逆 平 喘). It is used for the treatment of oriental dryness and abdominal pain, abdominal distension, acute enteritis, seaweed (cough) and the like as dried persimmon, digestion, , Pyeongsan acid, and ash inhaling.

Examples of the components of the hippophae tree so far known include β-eudesmol, magnolol, honokiol, magnocurarine, tannin and the like, Magnolol and honokiol have proved to be safer and more effective than conventional antibiotics such as chlorohexidine (Korean Patent Publication No. 1999-1000001). Various studies have been carried out on the basis of the pharmacological action of the above-described foal. Korean Patent Publication No. 1999-1000001 discloses an antimicrobial agent, Korean Patent Publication No. 2000-61656 discloses a composition for cancer treatment, Korean Patent Publication No. 1990 -1377 was used as a component of a therapeutic composition for tuberculosis, and Korean Patent No. 0919625 was used as a component of a therapeutic agent for fatty liver disease. In addition, various uses are known as acquired immunodeficiency syndromes (Korean Patent Laid-Open No. 1993-122) and hairy products (Korean Patent Laid-Open No. 2001-30194).

Examples of the crude extract or the crude extract are those prepared by extracting the crude oil with water or C1 to C4 lower alcohol and then concentrating the mixture under reduced pressure or using ethyl acetate or the like, Since it is a viscous extract having a high viscosity and high tackiness, it is difficult to produce a precise amount because it is adhered to a mechanism during weighing and manufacturing, and a lot of effort is required to wash the adhered raw material. In the preparation process, sticking, there are problems such as capping and laminating, and problems of coupling in raw material and coating are caused. In particular, in the case of the old-age soft-drink extract, the alcohol used in the preparation of the back- There is a problem in that there is a limitation in removing an organic solvent such as ethyl acetate.

The present invention is based on the finding that, even if a supersaturated soft X-ray extract is contained in a high content, it does not cause problems such as a tableting disorder, a raw material oozing, a coupling at the time of coating, It is an object of the present invention to provide a solid preparation for oral administration containing soft X-rays.

The present invention provides a solid oral preparation containing an oral dosage form containing 10 to 100 parts by weight of an adsorbent material selected from calcium silicate and silicon dioxide, based on 100 parts by weight of the crude skin lotion extract.

The starch used in the preparation of the skim milk extract of the present invention is selected from the group consisting of Magnolia obovata Thunberg, Magnolia officinale Rehder et Wils, and Machilus thunbergii Sieb. Et Zucc It can be used either cultivated or commercially available.

It is preferable that the after-treatment soft drink extract of the present invention is a fraction of ethyl acetate extracted with ethyl acetate after extracting water, C ₁ to C ₄ lower alcohol or a mixture thereof with a solvent. The lower alcohol is more preferably ethanol or methanol, and most preferably ethanol. It is preferable to add 3 to 5 times of water, alcohol, or a mixture thereof to the dried skimmed milk after 2 to 10 times the weight of the skimmed milk. Do not. The extraction temperature is preferably 30 ° C to 100 ° C, more preferably 80 ° C to 100 ° C, but is not limited thereto. The extraction time is preferably from 1 hour to 5 hours, more preferably from 2 hours to 3 hours, but is not limited thereto. The extraction method may be a cold extraction, an ultrasonic extraction or a reflux cooling extraction method, and it is preferable to use a reflux cooling extraction method. The number of times of extraction is preferably 1 to 5 times, more preferably 4 times, but is not limited thereto.

The solid preparation for oral administration of the present invention contains 5000 ppm or less, preferably 1000 ppm or less, more preferably 600 ppm or less of the alcohol as the residual solvent, Preferably not more than 500 ppm, more preferably not more than 200 ppm. It is very difficult to increase the drying time in order to remove or reduce the residual solvent of alcohol or ethyl acetate in the soft X-ray irradiated X-ray irradiated X-ray, or to regulate it below the upper limit value even if the drying temperature is increased.

The inventive deep-fried soft-boiled extract contains 10 to 35% by weight, preferably 12 to 34% by weight of magneol and honokiol as index components in the dry solid. The oral solid preparation containing the supernatant extract of the present invention contains 10 to 2000 mg, preferably 50 to 600 mg, more preferably 50 to 300 mg of the supernatant lotion extract per unit dosage form.

 In addition, the solid oral preparation containing the supernatant extract of the present invention contains 10 to 100 parts by weight, preferably 20 to 50 parts by weight, more preferably 20 to 30 parts by weight, of the adsorbed material with respect to 100 parts by weight of the soft X-ray. Below the lower limit, problems such as sticking, capping, laminating, and the like may occur. Coupling problems arise when the raw material comes out and coated, and residues such as alcohol and ethyl acetate It is difficult to lower the solvent content to 5000 ppm or less and the effect of preventing the tableting ability or the raw material from coming out is not improved even though the above weight part is exceeded and the use of the excipient is restricted during the production of the formulations.

As the adsorbent, substances such as calcium silicate, silicon dioxide, kaolin, aluminum oxide, aluminum hydroxide, aluminum phosphate, abatosphate, bentonite, magnesium aluminum silicate and saponite may be used, and calcium silicate, silicon dioxide , And most preferably, calcium silicate is used at a lower content, it is possible to achieve the improvement of the tableting ability and the effect of preventing the raw material from coming out, and the effect of removing the organic solvent is also excellent. On the other hand, a cellulose adsorbing material such as microcrystalline cellulose or a saccharide such as lactose or dextrin has a significantly larger amount than calcium silicate or silicon dioxide in order to improve the tableting ability at a level similar to that of calcium silicate or silicon dioxide, There is a problem in that it is difficult to add an effective amount to the dosage form or to increase the size of the dosage form by limiting the usage amount of the super soft dose extract per unit dosage form.

The present invention can be formulated into tablets, granules and hard capsules as oral solid dosage forms, and can be formulated in tablet form, preferably. In addition to one or more pharmaceutically acceptable excipients, carriers, diluents, disintegrants, lubricants, stabilizers, antioxidants, flavoring agents, coloring agents, coloring agents, Preservatives, perfumes, sweeteners, pigments, pH adjusting agents, viscosity adjusting agents, and the like. The above-mentioned substances to be added may be substances which are usually used pharmacologically within a range not adversely affecting the pharmaceutical efficacy, and it is preferable to add them in a usual amount to be usually used for the preparation. The disintegrant acts to speed up the disintegration due to the polymer and the after-treatment soft X-ray, and it can be used as an antioxidant such as alginate such as alginic acid and calcium alginate, carboxymethylcellulose calcium salt, chitosan, croscarmellose sodium, crospovidone, , Low substituted hydroxypropyl cellulose, methyl cellulose, starch glycolate, sodium starch glycolate, and the like, but is not limited thereto. Preferably one or more selected from the group consisting of croscarmellose sodium and sodium starch glycolate.

The present invention also provides a method for preparing a solid preparation for oral use, which comprises mixing a high-content crude soft extract and an adsorbent and pulverizing them, and then formulating them. More particularly, the present invention relates to a method for producing a soft ice-cream extract, which comprises mixing 100 parts by weight of an after-treatment soft drink extract and 20 to 50 parts by weight of water, a lower alcohol of C ₁ to C ₄ , 10 to 100 parts by weight of an adsorbent selected from calcium silicate and silicon dioxide is pulverized while mixing and dried at 30 to 90 DEG C to the fluidized skimmed fiber soft extract; And formulating the dried powder.

The after-treatment soft-drink extract is preferably an ethanol extract of Lycoris chejuensis or an ethyl acetate fraction obtained by dissolving it in ethyl acetate, and ethanol or ethanol aqueous solution is preferably used as a solvent for imparting the flowability.

In the present invention, the content of the remaining solvent such as alcohol or ethyl acetate can be remarkably lowered by mixing the after-treatment soft X-ray extract with the silica adsorbing material and drying at 30 to 90 ° C, preferably 50 to 70 ° C.

The step of preparing the dried powder may be carried out by a general manufacturing method such as a wet granulation method, a dry granulation method, an extrusion molding method or a direct method. When the density of the adsorbent used in the preparation of oral solid preparations is high, the preparation may be carried out using the direct method instead of the dry granulation method. Preferably, a manufacturing method such as a dry granulation method or an extrusion molding method may be used.

The solid preparation for oral administration containing the capsicum extract according to the present invention does not cause changes in hardness and texture and thus improves the storage stability. Even when the capsicum softex extract contains a high content, it is prepared without bad fluidity and fixation problems, When formulating into a general manufacturing facility, it is industrially useful in size and can be produced without manufacturing problems.

Advantages and features of the present invention and methods of achieving them will become apparent with reference to the embodiments described in detail below. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims.

Preparation Example 1: Preparation of an after-treatment soft-drink extract

8 kg of ethanol was added to 1 kg of dried skins purchased from Kyungdong market, and the mixture was reflux cooled for 3 hours at 80 ℃. The reflux-cooled extract was filtered using a filter paper (Advantec no. 2 filter paper), and the filtrate was concentrated under reduced pressure using an evaporator (EYELA, N-1000, Japan) and dried to prepare a crude ethanol extract.

The crude ethanol extract was dispersed in water, and the residue was partitioned with ethyl acetate. The ethyl acetate-soluble fraction was concentrated under reduced pressure to obtain the crude ethyl acetate fraction.

Preparation Example 2: Preparation of a granule containing skim milk extract using calcium silicate

30 g of ethanol was mixed with 100 g of the crude extract of Preparation Example 1 to obtain fluidity and then adsorbed material of any one of calcium silicate (Tomita Pharma, FLORITE R), silicon dioxide, lactose and microcrystalline cellulose was measured, And then granulated using a 20 mesh net, dried at 60 ° C for 15 hours, and then passed through a 20 mesh net to prepare granules.

division Weight ratio 1: 0.1 1: 0.2 1: 0.5 1: 1 1: 2 (G) 91 83 71 50 33 Adsorbed material content (g) 9 17 29 50 67 Total amount 100 100 100 100 100

The calcium silicate (Tomita Pharma, FLORITE R) has a Loose Bulk Density of 0.07 g / mL, a Tapped Bulk Density of 0.11 g / mL, a Surface Area of 140 m ² / g, D10: 22, D30: 26, D50: 28, D70: 33, D90: 41, and the pH of the 5% deionized water dilution was 9.2.

Experimental Example 1: Property Comparison

The properties of the granules prepared in Preparation Example 2 were visually observed and classified into liquid phase, semi-solid phase and solid phase.

division Weight ratio 1: 0.1 1: 0.2 1: 0.5 1: 1 1: 2 Calcium silicate elegance elegance elegance elegance elegance Silicon dioxide Semi-solid elegance elegance elegance elegance Lactose Liquid phase Liquid phase Liquid phase Semi-solid elegance Microcrystalline cellulose Liquid phase Liquid phase Liquid phase Semi-solid elegance

Table 3 shows the results of tactile test when the granules prepared in Preparation Example 2 were hand-pressed by the user and the case where the supernatant X-ray exuded (Fail), and the case where the exudate did not escape was considered as Good.

division Weight ratio 1: 0.1 1: 0.2 1: 0.5 1: 1 1: 2 Calcium silicate Good Good Good Good Good Silicon dioxide Fail Good Good Good Good Lactose Fail Fail Fail Fail Good Microcrystalline cellulose Fail Fail Fail Fail Good

As a result of the visual inspection and the tactile examination, even when only 10 parts by weight of 100 parts by weight of the crude skin lotion extract was mixed, the granules were suitable for the preparation of solid preparations in calcium silicate and 20 parts by weight or more in the case of silicon dioxide. And 200 parts by weight in the case of microcrystalline cellulose, it can be used for the production of solid preparations.

Experimental Example 2: Fluidity comparison

The flowability of the granules prepared in Preparation Example 2 was measured using an angle-of-inclusive meter (GTB, ERWEKA GmbH), and the angle of repose was measured in terms of angle (°).

division Weight ratio 1: 0.1 1: 0.2 1: 0.5 1: 1 1: 2 Calcium silicate 43 40 39 38 37 Silicon dioxide 55 44 42 39 38 Lactose Not measurable Not measurable Not measurable 60 47 Microcrystalline cellulose Not measurable Not measurable Not measurable 60 48

As a result of the fluidity measurement, it was found that the granules were suitable for the preparation of the solid preparation in the case of calcium silicate, and more than 20 parts by weight in the case of the silicon dioxide, even when only 10 parts by weight were mixed with 100 parts by weight of the after- , It was confirmed that it was used in the production of the solid preparation in the ratio of 200 parts by weight when mixed, and it was confirmed that the fluidity was not good enough to cause disorder in the process at less than 200 parts by weight.

Experimental Example 3: Comparisons of Precision

Lactose and a small amount (1 mg / g) of magnesium stearate were mixed with the granules and the excipient prepared in Preparation Example 2 to prepare 500 mg tablets such that the content of the latex extract was 150 mg. Table 5 shows whether tablets were formed during tableting, capping, laminating, or the like.

division Weight ratio 1: 0.1 1: 0.2 1: 0.5 1: 1 1: 2 Calcium silicate none none none none none Silicon dioxide none none none none none Lactose No puncture No puncture Sticking Sticking Sticking Microcrystalline cellulose No puncture No puncture No puncture Sticking Sticking

As can be seen from Table 5, when calcium silicate was mixed, there was no penile disorder even when only 10 parts by weight of 100 parts by weight of the after-treatment soft X-ray was mixed. In the case of silicon dioxide, However, in the case of lactose or microcrystalline cellulose, it was confirmed that even when 100 parts by weight of lactose or microcrystalline cellulose was blended, the dysphagia appeared.

Experimental Example 4: Comparison of residual solvent content

The residual solvent content of the sample of the dry limit value at which the remaining solvent content did not decrease and the sample of the calcium silicate or silicon dioxide of Production Example 2 added in the content of Table 1 were dried at 60 캜, The results are shown in Table 6. The amount of the residual solvent was expressed in ppm in the amount of residual solvent in 1 g of the crude soft X-ray.

500 mg of ethanol ethanol and 500 mg of ethyl acetate were precisely weighed and dissolved in N, N-dimethylformamide to give 100 mL. 5 mL of this solution was taken in a 100 mL volumetric flask, and the solution was condensed with N, N-dimethylformamide, 5 mL of this solution was precisely taken into a vial for headspace and sealed with a septum and a metal cap to prepare a standard solution. Add approximately 500 mg of sample to the headspace vial. 5 mL of N, N-dimethylformamide is precisely taken, placed in a vial, sealed with a septum and a metal cap, sonicated to prepare a sample solution, The ethanol and ethyl acetate contents were analyzed by chromatography.

division Mixing ratio
(Crude protein extract: adsorbent material) Ethyl acetate
(ppm) ethanol
(ppm) Smooth skin tone 1: 0 512 10756 Skewed soft X: Calcium silicate 1: 0.1 15 994 1: 0.2 Non-detection 583 1: 0.5 Non-detection 489 1: 1 Non-detection 512 1: 2 Non-detection 468 Extra soft X: Silicon dioxide 1: 0.1 20 1204 1: 0.2 15 896 1: 0.5 16 439 1: 1 Non-detection 457 1: 2 Non-detection 508

It was also found that the residual solvent content was not decreased even after drying at 60 ° C. for 36 hours in the case of the after - treatment soft ice - extract, and the ethanol content remained more than 1% by weight. However, even when calcium silicate or silicon dioxide was mixed with the after-treatment soft drink extract and dried for 15 hours at 60 DEG C as in Production Example 2, the ethyl acetate or ethanol content was remarkably decreased to 1/10 to 1/30 or less, It was found that when the amount of calcium or silicon dioxide was 20 parts by weight or more based on 100 parts by weight of the crude soft drink extract, the amount of the residual solvent was further reduced.

Claims (9)

Wherein the composition contains 10 to 100 parts by weight of calcium silicate,
Wherein the after-treatment soft-extract extract is an ethyl acetate fraction of an after-treatment extract.
And 20 to 100 parts by weight of silicon dioxide, based on 100 parts by weight of the crude soft ice-cream,
Wherein the after-treatment soft-extract extract is an ethyl acetate fraction of an after-treatment extract.
delete According to claim 1 or 2, wherein the Magnolia soft X is water, C ₁ to C ₄ lower alcohol or extract the Magnolia a mixture thereof as a solvent, magnolia, characterized in that the ethyl acetate fraction was extracted with ethyl acetate Soft solid preparations containing soft X - rays.
The solid preparation for oral administration of the present invention according to claim 4, which contains not more than 5000 ppm of the alcohol and not more than 5000 ppm of ethyl acetate as a residual solvent.
The solid preparation for oral administration according to any one of claims 1 to 3, which contains 10 to 2000 mg of the after-treatment soft dose extract per unit dosage form.
delete Mixing 100 parts by weight of the crude soft ice-containing extract with 20 to 50 parts by weight of water, a lower alcohol of C ₁ to C ₄ , or a mixture thereof to impart fluidity to the after-treatment soft drink extract;
10 to 100 parts by weight of calcium silicate is pulverized while mixing with the fluidized skimmed fiber soft X-ray powder and dried at 30 to 90 캜; And
And formulating the dried powder,
Wherein the after-treatment soft-drink extract is an ethyl acetate fraction of an after-treatment extract.
Mixing 100 parts by weight of the crude soft ice-containing extract with 20 to 50 parts by weight of water, a lower alcohol of C ₁ to C ₄ , or a mixture thereof to impart fluidity to the after-treatment soft drink extract;
Powdering 20 to 100 parts by weight of silicon dioxide into the flowability-imparted superfine soft-drink extract and drying at 30 to 90 캜; And
And formulating the dried powder,
Wherein the after-treatment soft-drink extract is an ethyl acetate fraction of an after-treatment extract.