JP4222802B2 - Pergolide-containing pharmaceutical composition - Google Patents

Description

【００２４】
また、表１に示す成分を用いた他は実施例１と同様にして、比較例１のペルゴリド含有医薬組成物を得た。
【００２５】
実施例１および比較例１で得られたペルゴリド含有医薬組成物を、無包装の状態で、表２に示す条件下で２週間または４週間放置した後、組成物中のペルゴリド量を測定した。なお、ペルゴリド量は、高速液体クロマトグラフ法により測定し、対イニシャル比を求めた。結果を表２に示す。
【００２６】
【表２】

【００２７】
表２に示されるように、実施例１の組成物は、比較例１の組成物に比べて光による分解が少なく、安定なものであることがわかる。
【００２８】
実施例２および比較例２〜７
ビーカーを用いてメシル酸ペルゴリド０．０１３ｇを３ｇの精製水に分散させた。上記分散液を乳糖５９．２ｇに添加して吸着させた。上記分散液の入っていたビーカーを精製水２ｇで洗浄し、それも乳糖に添加した。乳糖に吸着させたメシル酸ペルゴリドに、結合剤の１５重量％水溶液５．３ｇを加えて混練し、６０℃で１時間乾燥させ、２２号篩で整粒し、実施例２および比較例２〜７のペルゴリド含有医薬組成物を作製した。
【００２９】
実施例２および比較例２〜７で用いた各結合剤を、表３に示す。なお、実施例２のポリビニルアルコールは、ポリビニルアルコール（部分けん化物）〔日本合成化学社製、商品名：ＰＶＡ（ＥＧ−０５Ｔ）、粘度４．８〜５．８ｃｐｓ、けん化度８６．５〜８９．０ｍｏｌ％〕を使用した。
【００３０】
【表３】

【００３１】
得られた各ペルゴリド含有医薬組成物について、下記のようにして、光に対する安定性の試験を行なった。
【００３２】
円柱状の透明なフタ付きのサンプル容器（直径：４．５ｃｍ）に、実施例２または比較例２〜７のペルゴリド含有医薬組成物の粉体をそれぞれ３ｇずつ水平になるように入れた後、フタをした。サンプル中の粉体層は、３〜４ｍｍであった。
【００３３】
各サンプルを蛍光下（２，０００Ｌｕｘ）で１週間もしくは２週間、またはＵＶ下で３日間放置した。
【００３４】
光に当てたサンプル中のペルゴリド含有組成物３ｇを均一に混ぜ合わせ、その１．５ｇを使用し、高速液体クロマトグラフ法により、ペルゴリド量を測定した。ペルゴリド量を初期値に対する比として求め、その結果を表４に示す。
【００３５】
【表４】

【００３６】
表４に示されるように、いずれもイニシャルに比べてペルゴリド量は低下するものの、実施例２のポリビニルアルコールを用いたペルゴリド含有医薬組成物は、光による分解が少なく安定なものであることがわかる。なかでも、実施例２の組成物は、結合剤として〔特許文献１〕に使用されているポリビニルピロリドンを用いた比較例２の組成物に比べても、光による分解がより少ないものであることがわかる。
【００３７】
【発明の効果】
本発明のペルゴリド含有医薬組成物は、光による分解が少なく安定なものであるという効果を奏する。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a pergolide-containing pharmaceutical composition and a method for stabilizing pergolide against light.
[0002]
[Prior art]
Pergolide is a compound having dopaminergic activity and is a useful compound as a therapeutic agent for Parkinson's disease. However, since pergolide-containing pharmaceutical compositions are unstable to light, it is inferior in stability when exposed to light when used across patients, simply by using an aluminum pillow in a clear PVC / aluminum PTP package. There is a drawback.
[0003]
In order to improve the instability to light, pergolide-containing pharmaceutical compositions have been proposed which are stabilized against degradation by light with a stabilizer selected from polyvinylpyrrolidone, α-tocopherol succinate and propyl gallate (For example, refer to Patent Document 1). However, this is not enough, and at present the double-sided aluminum PTP packaging is used.
[0004]
[Patent Document 1]
Japanese Unexamined Patent Publication No. 1-146821 (first page)
[0005]
[Problems to be solved by the invention]
This invention is made | formed in view of the said prior art, and it aims at providing the pharmaceutical composition containing pergolide excellent in stability with few decomposition | disassembly by light.
[0006]
[Means for Solving the Problems]
That is, the gist of the present invention is as follows.
[1] Pergolide-containing pharmaceutical composition comprising pergolide or a pharmaceutically acceptable salt thereof and polyvinyl alcohol, and [2] blending polyvinyl alcohol with pergolide or a pharmaceutically acceptable salt thereof. A method for stabilizing pergolide against light, characterized by
About.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
The pergolide-containing pharmaceutical composition of the present invention (hereinafter also simply referred to as a composition) is a composition that is stabilized against degradation by light without using a separate stabilizer by using polyvinyl alcohol as a binder. It has the advantage that things can be obtained.
[0008]
The pharmaceutically acceptable salt of pergolide is not particularly limited. For example, in addition to pergolide mesylate, sulfate, nitrate, phosphate, acetate, propionate, caprylate, oxalate, Examples include malonate, phenylacetate, citrate, lactate, malate, tartrate, maleate, methanesulfonate, toluenesulfonate, etc., either alone or in combination. May be used.
[0009]
The polyvinyl alcohol is not particularly limited, but preferably has a polymerization degree of 1000 or less from the viewpoint of solubility in water at room temperature and the viscosity of an aqueous solution. Polyvinyl alcohol may be a partially saponified product as well as a completely saponified product. The partially saponified product refers to, for example, a polymer obtained by saponifying polyvinyl acetate and having a saponification degree of 78 to 96 mol%.
[0010]
The content of pergolide or a pharmaceutically acceptable salt thereof in the pergolide-containing pharmaceutical composition is arbitrary, for example, it is easy to administer 0.01 to 6 mg of pergolide per day as a therapeutically effective dose in a single or divided dose. A certain amount is preferred.
[0011]
The content of polyvinyl alcohol in the pergolide-containing pharmaceutical composition is preferably 0.1 to 5% by weight in order to obtain good stabilization of the pergolide-containing pharmaceutical composition with respect to light and to obtain favorable characteristics of the pharmaceutical composition. 0.3-2 weight% is more preferable, and 0.5-1 weight% is further more preferable.
[0012]
In the composition of the present invention, various excipients, disintegrating agents, coloring agents, lubricants and the like generally used in pharmaceutical compositions can be arbitrarily used.
[0013]
As the excipient, those generally used as an excipient can be used. Of these, sugars such as lactose, sucrose and sucrose, and starches such as corn starch and partially pregelatinized starch are preferred.
[0014]
As the disintegrant, those generally used as disintegrants can be used. For example, croscarmellose sodium, carmellose calcium, carmellose sodium, low-substituted hydroxypropylcellulose, sodium carboxymethyl starch, corn starch, crystalline cellulose, partially pregelatinized starch and the like can be mentioned.
[0015]
Examples of the colorant include yellow ferric oxide, edible yellow No. 4 aluminum lake, blue No. 2 aluminum lake, and the like, and may be added as necessary.
[0016]
Examples of the lubricant include magnesium stearate, stearic acid, talc, calcium stearate, hydrogenated oil, sucrose fatty acid ester, and the like, and may be added as necessary.
[0017]
The composition of the present invention can be obtained by adding and mixing the above-mentioned pergolide or a pharmaceutically acceptable salt thereof, polyvinyl alcohol and various optional components by a known method. For example, pergolide or a pharmaceutically acceptable salt thereof and various optional components are added and mixed, and then an aqueous solution of polyvinyl alcohol is added and kneaded. Next, the composition of the present invention can be obtained by drying and sizing the obtained kneaded product. The obtained composition may be used as a powder as it is, or may be filled into a capsule to form a capsule, or may be compressed into a tablet.
[0018]
Examples of the form of the composition of the present invention include tablets, capsules, powders and the like.
[0019]
The composition of the present invention obtained as described above is stabilized against light. Therefore, according to the present invention, there is provided a method for stabilizing pergolide against light, which comprises blending polyvinyl alcohol with pergolide or a pharmaceutically acceptable salt thereof.
[0020]
【Example】
Next, the present invention will be described in more detail based on examples, but the present invention is not limited to such examples.
[0021]
Example 1 and Comparative Example 1
0.0653 g of pergolide mesylate was dispersed in 30 g of purified water. Lactose 15g and yellow ferric oxide 0.15g were triturated with No. 60 sieve and then added to the high speed mixer. Further, 274.5 g of the remaining lactose, 6 g of croscarmellose sodium, and 1 g of DL-methionine were added and mixed using a high speed mixer. A dispersion of the above-mentioned pergolide mesylate was added to the resulting mixture and kneaded, and further polyvinyl alcohol (partially saponified product) [manufactured by Nippon Synthetic Chemical Co., Ltd., trade name: PVA (EG-05T), viscosity 4.8-5 0.8 gps, saponification degree 86.5-89.0 mol%] was added and kneaded with 20 g of a 10 wt% aqueous solution. The obtained kneaded product was pulverized, passed through a No. 8 sieve, dried with a shelf dryer, and sized using a No. 22 sieve. Add 1.5 g of magnesium stearate to the obtained particles, mix with a V-type mixer, and then 300.0 mg / T with a rotary tableting machine (deformation: major axis 11.6 mm, minor axis 6.3 mm, with secant) The pergolide-containing pharmaceutical composition of Example 1 was obtained.
[0022]
Table 1 shows the amount and content of each component in one tablet of the obtained pergolide-containing pharmaceutical composition.
[0023]
[Table 1]

[0024]
Moreover, the pergolide containing pharmaceutical composition of the comparative example 1 was obtained like Example 1 except having used the component shown in Table 1. FIG.
[0025]
The pergolide-containing pharmaceutical composition obtained in Example 1 and Comparative Example 1 was left unpacked for 2 weeks or 4 weeks under the conditions shown in Table 2, and then the amount of pergolide in the composition was measured. In addition, the amount of pergolide was measured by the high performance liquid chromatograph method, and the initial ratio was determined. The results are shown in Table 2.
[0026]
[Table 2]

[0027]
As shown in Table 2, it can be seen that the composition of Example 1 is less stable than light of the composition of Comparative Example 1 and is stable.
[0028]
Example 2 and Comparative Examples 2-7
Using a beaker, 0.013 g of pergolide mesylate was dispersed in 3 g of purified water. The dispersion was added to 59.2 g of lactose and adsorbed. The beaker containing the dispersion was washed with 2 g of purified water and added to lactose. To pergolide mesylate adsorbed on lactose, 5.3 g of a 15% by weight aqueous solution of a binder was added and kneaded, dried at 60 ° C. for 1 hour, sized with No. 22 sieve, Example 2 and Comparative Example 2 Seven pergolide-containing pharmaceutical compositions were prepared.
[0029]
Table 3 shows the binders used in Example 2 and Comparative Examples 2 to 7. The polyvinyl alcohol of Example 2 is polyvinyl alcohol (partially saponified product) [manufactured by Nippon Synthetic Chemical Co., Ltd., trade name: PVA (EG-05T), viscosity 4.8 to 5.8 cps, saponification degree 86.5 to 89. 0.0 mol%] was used.
[0030]
[Table 3]

[0031]
About each obtained pergolide containing pharmaceutical composition, the stability test with respect to light was done as follows.
[0032]
After putting the powder of the pergolide-containing pharmaceutical composition of Example 2 or Comparative Examples 2 to 7 horizontally into a cylindrical sample container (diameter: 4.5 cm) with a transparent lid, I covered it. The powder layer in the sample was 3-4 mm.
[0033]
Each sample was left under fluorescence (2,000 Lux) for 1 or 2 weeks or under UV for 3 days.
[0034]
3 g of the pergolide-containing composition in the sample exposed to light was mixed uniformly, 1.5 g of the composition was used, and the amount of pergolide was measured by high performance liquid chromatography. The amount of pergolide was determined as a ratio to the initial value, and the results are shown in Table 4.
[0035]
[Table 4]

[0036]
As shown in Table 4, although the amount of pergolide is lower than that of the initial, the pergolide-containing pharmaceutical composition using the polyvinyl alcohol of Example 2 is found to be stable with little degradation by light. . In particular, the composition of Example 2 is less decomposed by light than the composition of Comparative Example 2 using polyvinylpyrrolidone used in [Patent Document 1] as a binder. I understand.
[0037]
【The invention's effect】
The pergolide-containing pharmaceutical composition of the present invention has the effect of being stable with little degradation by light.

Claims (3)

A pergolide-containing pharmaceutical composition comprising pergolide or a pharmaceutically acceptable salt thereof and polyvinyl alcohol. The pergolide-containing pharmaceutical composition according to claim 1, wherein the content of polyvinyl alcohol is 0.1 to 5% by weight. A method for stabilizing pergolide against light, which comprises blending pergolide or a pharmaceutically acceptable salt thereof with polyvinyl alcohol.