JPH02286621A - Oral cholesterol lowering agent - Google Patents

Abstract

PURPOSE:To obtain a readily administrable oral cholesterol lowering agent, containing an anion exchange resin, hydrophobic substance and binder and stable at ambient temperature. CONSTITUTION:The objective tablet obtained by mixing an anion exchange resin with a small amount of a hydrophobic substance and a binder, adding and mixing water or a binding solution so as to contain 3-16%, preferably 5-12% water therein, further adding a flow improving agent, etc., and tableting the resultant mixture. A highly fatty acid, metal salt or glycerol ester thereof, higher alcohol, etc., are used as the hydrophobic substance and the amount thereof blended is preferably 3-10% based on the weight of the total pharmaceutical. Hydroxypropyl cellulose, PVA, polyvinylpyrrolidone, alpha-starch, arginine, dextrin, etc., are used as the binder and the amount thereof blended is preferably 3-15% based on the weight of the total pharmaceutical.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a pharmaceutical composition for an oral cholesterol-lowering agent that is easy to take. The present invention relates to a cholesterol-lowering agent containing a hydrophobic substance and a binder as active ingredients.

[Problems to be solved by conventional technology and invention]

Conventionally, it has been known to use anion exchange resins as cholesterol-lowering agents for lowering blood cholesterol (see, for example, Japanese Patent Application Laid-Open No. 60-209523).

Conventionally, preparations that are suspended and administered have also been put into practical use. In addition, regarding anion exchange resin tablets, a hydrophobic substance such as wax is melted, an anion exchange resin is kneaded into it, and a flow improver such as Aerosil is further mixed.
A method of granulating and then forming into tablets is known.

However, the above method requires a large amount of hydrophobic substance and has the disadvantage that the manufacturing method is complicated.

[Failure to solve the problem]

In view of the above-mentioned problems, the present inventors have made extensive studies and have found that
After mixing a small amount of a hydrophobic substance and a binder with an anion exchange resin, water or a binder is added and mixed so that the water content is 3 to 16%, preferably 5 to 12%, and a flow improver, etc. is added. We have found a composition of tablets that are easy to take and stable at room temperature using a simple manufacturing method that involves post-compression.

In other words, it is known that anion exchange resins swell due to moisture absorption, and when granules containing dried anion exchange resins are compressed into tablets, they swell significantly at room temperature (relative humidity 50-70%), and the hardness of the tablets also decreases. do. However, as in the present invention, tablets that are stable at room temperature can be obtained by pre-impregnating granules with an appropriate amount of water and then compressing them. It was also found that the moldability of tablets was significantly improved by incorporating an appropriate amount of water. If the water content of the tablet is less than 3%, hygroscopic swelling will be significant, and if it is more than 16%, sticking will occur during tablet compression.

Hydrophobic substances used in the present invention include higher fatty acids such as stearic acid, metal salts of higher fatty acids such as magnesium stearate, higher fatty acid glycerin esters such as hydrogenated castor oil, higher alcohols such as stearyl alcohol, and carbonized paraffin. Hydrogen and waxes such as carnauba wax are preferably used, and these hydrophobic substances may be used alone or in combination. The amount of hydrophobic substance to be used is 2 to 2 to the weight of the entire formulation.
It is preferable to use 50%, especially 3 to 10%.

Also, pharmaceutical organic or inorganic solid or liquid carriers or diluents suitable for administration can be used in their preparation. For example, excipients used in producing solid preparations include lactose, mannitol, corn starch, potato starch, phosphoric acid, calcium hydrogen, microcrystalline cellulose, white sugar, aluminum silicate, magnesium silicate, etc. As the disintegrant, carboxymethyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, hydroxypropyl cellulose sodium carboxymethyl starch, etc. are used.

Examples of the binder include polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, polyvinylalcohol, pregelatinized starch, arginine, dextrin, gelatin, hydroxypropyl starch, vinyl acetate, gum, and the like. The binder is preferably used in an amount of 1 to 50%, particularly 3 to 15%, based on the total weight of the preparation.

Tablets can be made without the use of lubricants, but commonly used talc, stearic acid, magnesium stearate, calcium stearate, and waxes may also be used. Moreover, acids can also be added as a pH adjuster.

In addition to the granulation methods listed above, a preferred granulation method is fluidized bed granulation.

Next, the composition was as described in Example 2 except that the water content was 2%, 4%, or 8%, and the weight was 660 mg.

Tablets with a diameter of 11 mmφ were compressed and stored at 25° C. for one week, and the relationship between the relative humidity in the storage atmosphere and the rate of change in diameter is shown in FIG.

As seen in FIG. 1, the change in diameter (swellability) of the tablet under each relative humidity decreases as the water content in the tablet increases.

Figure 2 also shows a sample with the same composition as above except for water, but with a weight of 66
A tablet of 0 mg and a tablet diameter of 11+nmφ was compressed with a compression force of 700 kg, and the relationship between the moisture content in the tablet and the tablet hardness (formability) is shown.

It can be seen from FIG. 2 that as the water content in the tablet increases from 4% to 11%, the formability of the tablet improves.

In addition, in the storage atmosphere when tablets with a weight of 660 mg and a tablet diameter of 11+++ mφ having the composition described in Example 2 except that the moisture content was 3% or 8% were compressed and stored at 25°C for one week. FIG. 3 shows the change in tablet hardness with respect to relative humidity.

It can be seen from FIG. 3 that the hardness of the tablet under each relative humidity becomes more stable as the moisture content of the tablet increases.

〔Example〕

The present invention will be specifically explained below with reference to Examples, but the present invention is not limited to the following Examples unless the gist thereof is exceeded.

Example 1 In a speed kneader, 250 g of anion exchange resin and 12.5 g of carnauba wax were added and mixed, followed by 20 g of hydroxypropylcellulose and 2.5 g of Carplex.
5g was added and mixed.

Thereafter, a solution prepared by dissolving 2.5 g of citric acid in 30 g of water was added and mixed.

Transfer the obtained mixture to a ν-type mixer and add 5 g of Carplex.
After adding and mixing 7.5 g of stearic acid, the mixture was compressed to obtain tablets that were comfortable to take and were stable against humidity.

Example 2 In a speed kneader, 250 g of anion exchange resin,
12.5 g of stearic acid was added and mixed, and further 8 g of Amycol C, 12 g of hydroxypropylcellulose, and 2.5 g of Aerosil were added and mixed.

30 g of the condensate was added and mixed.

The resulting mixture was transferred to a ν-type mixer and Carplex 5
g1 Lovely Wax 101 (Freund Sangyo) 7.5
g was added, mixed, and tableted to obtain tablets that were comfortable to take and stable under humidity.

Example 3 In a Henschel mixer, 1 kg of anion exchange resin and 10,150 g of Lovelywax were mixed, followed by 20 g of Carplex, 40 g of hydroxypropyl cellulose.
g and mixed.

The mixture was transferred to a fluid bed granulation dryer and granulated with 7% hydroxypropyl cellulose.

A Moist Watch (manufactured by Okawara Seisakusho) was installed in the fluidized bed granulation dryer to control the moisture content of the granules at 10% during drying.

By compressing the obtained granules, tablets with a good feeling of taking and stable against humidity were obtained.

[Brief explanation of drawings]

Figure 1 shows the relationship between tablet moisture and changes in tablet diameter, Figure 2 shows the relationship between tablet moisture and moldability, and Figure 3 shows the relationship between tablet moisture and tablet hardness. FIG. Patent Applicant Mitsubishi Kasei Corporation Representative Keito Yoshimine
Matsu 1) Major Procedural Amendment January 29, 1990 Yoshi, Commissioner of the Patent Office 1) Takeshi Moon 1, Indication of the case 1999 Patent Application No. 104734 2, Name of the invention Oral cholesterol-lowering agent 3, Person making the amendment Relationship to the case Name of patent applicant (596) Mitsubishi Kasei Co., Ltd. Date 7 Contents of amendment 1) The detailed description of the invention column is amended as follows. “2%, 4%, or 8%” on page 6, line 9 of the specification is changed to “6.
5% or 10.6%”. (2) “3% or 8%” on page 7 line 4 of the specification is 16.5
% or 10.6%”. (3) "Weight: 660 mg" on page 7, line 5 of the specification [
The weight is corrected to 660 mgJ. 2) Amend the drawings as shown in the attached drawings. 5. Date of amendment order Voluntary amendment 6. Subject of amendment

Claims (1)

[Scope of Claims] 1. An oral cholesterol-lowering agent containing an anion exchange resin, a hydrophobic substance, and a binder as essential components. 2. The oral cholesterol-lowering agent according to claim 1, which has a water content of 3 to 16% by weight. 3. The hydrophobic substance is a higher fatty acid, a metal salt of a higher fatty acid,
3. The oral cholesterol-lowering agent according to claim 1, which comprises one or more substances selected from the group consisting of glycerin esters of higher fatty acids, higher alcohols, hydrocarbons, and waxes. 4. The binder is one or two selected from the group consisting of hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, pregelatinized starch, arginine, dextrin, gelatin, gum, hydroxypropyl starch, and vinyl acetate. The oral cholesterol-lowering agent according to claim 1, 2 or 3, which comprises at least one substance. 5. The oral cholesterol-lowering agent according to claim 1, 2, 3 or 4, which is in the form of a tablet.