JP4102461B2 - Antipyretic - Google Patents

Description

【００１５】
対照群の発熱係数は平均４．８４であったが、イブプロフェン１mg／kg及び南天実エキス２５０mg／kg単独投与群の発熱係数は、それぞれ平均２．２９及び３．３７であり、両被験薬の解熱作用が認められた（相対指数：０．４７２及び０．６９６）。これら両薬剤の併用投与では解熱作用は更に強く認められ、その相対指数（０．２３０）は、それぞれ単独投与した時の相対指数の積（０．４７２×０．６９６＝０．３２９）よりも小さく、相乗作用が認められた。
【００１６】
実施例２
被験薬として、単独投与群には南天実エキス２５０mg／kg、アセトアミノフェン５０mg／kgを、併用投与群には南天実エキス２５０mg／kg及びアセトアミノフェン５０mg／kgを投与した以外は実施例１と同様にして、ラットの直腸温を測定した。結果を図２に、発熱係数、抑制率及び相対指数を表２に示す。
【００１７】
【表２】

【００１８】
対照群の発熱係数は平均４．９７であったが、アセトアミノフェン５０mg／kg及び南天実エキス２５０mg／kgを単独投与した場合、それぞれの発熱係数は平均４．４８及び３．８８であり、両薬剤は解熱作用を示した（相対指数：０．９０３及び０．７８２）。これら両薬剤の併用投与では解熱作用は更に強く認められ、その相対指数（０．５３０）は、それぞれを単独投与した時の相対指数の積（０．９０３×０．７８２＝０．７０６）よりも小さく、相乗作用が認められた。
【００１９】
製造例１
アセトアミノフェン９００mg、南天実乾燥エキス−３０（実施例１で使用したものと同じ）２５０mg、乳糖２１８mg、結晶セルロース１８０mg、カルメロースカルシウム１８０mg、ヒドロキシプロピルセルロース５４mgを攪拌造粒機内で均一に混合した。この混合物にアルコールを添加して造粒し、流動層造粒機で乾燥し、造粒物を整粒機を用いて整粒後、ステアリン酸マグネシウム１８mgを混合して打錠用顆粒を調整した。この打錠用顆粒を直径８．０mmの杵を用いて１錠２００mgに打錠した。
【００２０】
【発明の効果】
南天抽出物は解熱作用を有し、副作用が少なく安全であることから解熱剤として有用である。
【図面の簡単な説明】
【図１】南天実エキス、イブプロフェンの解熱作用を示す図である。
【図２】南天実エキス、アセトアミノフェンの解熱作用を示す図である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an antipyretic agent.
[0002]
[Prior art and problems to be solved by the invention]
Nanten has long been known for its various medicinal properties, and its fruits and leaves have been heavily used as folk medicine. In particular, domestine contained in fruits has sensory nerve and peripheral nerve palsy effects and is known to be effective in the prevention of asthma, whooping cough, bronchitis, etc. Tablets are commercially available.
In recent years, it has been reported that Nantenin present in Minami Tenjin has a sympathetic nerve blocking action and is effective as a blood pressure lowering agent (Japanese Patent Laid-Open No. 58-183617).
However, it is not known at all that Minami Tenmi has an antipyretic action.
[0003]
On the other hand, various drugs have conventionally been used as antipyretic agents, but most of the substances obtained by chemical synthesis have the disadvantage that side effects such as sleepiness and digestive problems are unavoidable.
[0004]
Therefore, an object of the present invention is to provide a drug having an excellent antipyretic action and high safety.
[0005]
[Means for Solving the Problems]
In view of such a situation, the present inventor has conducted extensive research and found that the Nanten extract has a sustained antipyretic action. Furthermore, when combined with acetaminophen or ibuprofen, it was found that a synergistic antipyretic action was exhibited, and the present invention was completed.
[0006]
That is, this invention provides the antipyretic agent which uses a southern sky extract as an active ingredient.
Moreover, this invention provides the antipyretic agent which uses a south sky extract and acetaminophen as an active ingredient.
Furthermore, this invention provides the antipyretic agent which uses a Nanten extract and ibuprofen as an active ingredient.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
Examples of the southern sky extract used in the present invention include a southern sky fruit and leaf extract, and the southern sky fruit extract is particularly preferable. Here, as the south Tenmi, any of White Minami Tenshin or Akana Minami may be used.
The Nanten extract can be obtained according to a conventional method using water, hot water, an organic solvent or the like. For example, it can be obtained by extracting dried Nanten fruit with ethanol, water, hot water, hydrous ethanol or the like. . What extracted Minami Tenjin with hydrous ethanol, especially 30% ethanol aqueous solution is preferable.
[0008]
In the present invention, a synergistic antipyretic action can be obtained by using a combination of Nanten extract and acetaminophen or ibuprofen. A preferred blending ratio of the Nanten extract (in terms of crude drug) and acetaminophen is 5000: 1 to 1: 100 by weight, and a more preferred blending ratio is 500: 1 to 1:10. Moreover, the preferable compounding ratio of a Nanten extract (raw ingredient conversion) and ibuprofen is 5000: 1 to 1:60 by weight ratio, and a more preferable compounding ratio is 500: 1 to 1: 6.
In addition to the essential components, the antipyretic of the present invention is a pharmaceutically acceptable carrier such as an excipient, a binder, a bulking agent, a disintegrant, a surfactant, a lubricant, a dispersant, a buffer, a preservative, A flavoring agent, a fragrance | flavor, etc. can be used in combination as appropriate. Examples of the dosage form include oral administration such as tablets, capsules, granules, powders, solutions, syrups, and parenteral administration such as suppositories.
[0009]
The dose of the antipyretic of the present invention varies depending on age, body weight, symptom, dosage form, number of administrations, etc., but when the Nanten extract is used as an active ingredient, it is usually 1 g per day for an adult in terms of a crude drug. 10g, 1.15g-11g in total per day for adults when using Nanten extract (converted as bulk drug) and acetaminophen as active ingredients, and Nanten extract (converted as drug substance) and ibuprofen as active ingredients In general, it is preferably 1.15 g to 10.6 g per day for an adult in general, and this is preferably administered once or divided into several times.
[0010]
The antipyretic agent of the present invention may be used for the purpose of antipyretic alone, but may be used as a general cold medicine by blending, for example, an anti-inflammatory agent, an analgesic agent, an antitussive expectorant, an antiallergic agent and the like as necessary. it can.
[0011]
【Example】
EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these.
[0012]
Example 1
After measuring the normal rectal temperature of Wistar male rats, a dry yeast suspension (20% w / v) suspended in physiological saline was subcutaneously administered in a volume of 10 ml / kg. On the next day, the test drug was orally administered to rats in which an increase in body temperature was observed, and the rectal temperature was measured over time until 4 hours thereafter (FIG. 1). The test drug is either South Tenmichi extract (extracted Minami Tenmi with 30% ethanol aqueous solution and then evaporated to remove the solvent, the same shall apply hereinafter) 250 mg / kg (5 g / kg in terms of drug substance) or ibuprofen. In the combined administration group, 1 mg / kg was suspended in 250 mg / kg of Nanten fruit extract and 1 mg / kg of ibuprofen in 0.5% CMC and administered in a volume of 5 ml / kg. The control group received the same volume of 0.5% CMC.
[0013]
The cumulative calorific value based on the normal body temperature up to 4 hours after administration is defined as the fever coefficient, and the suppression rate and relative index are shown in Table 1.
[0014]
[Table 1]

[0015]
The fever coefficient of the control group averaged 4.84, but the fever coefficient of the ibuprofen 1 mg / kg and Nantan real extract 250 mg / kg single administration groups averaged 2.29 and 3.37, respectively. An antipyretic effect was observed (relative index: 0.472 and 0.696). The antipyretic effect is more strongly observed in the combined administration of these two drugs, and the relative index (0.230) is higher than the product of the relative indices when each is administered alone (0.472 × 0.696 = 0.329). Small and synergistic.
[0016]
Example 2
As a test drug, Example 1 was administered except that the single administration group was administered with 250 mg / kg of Nanten fruit extract and 50 mg / kg of acetaminophen, and the combined administration group was administered with 250 mg / kg of Nanten fruit extract and 50 mg / kg of acetaminophen. In the same manner, the rectal temperature of the rat was measured. The results are shown in FIG. 2, and the exothermic coefficient, inhibition rate, and relative index are shown in Table 2.
[0017]
[Table 2]

[0018]
The fever coefficient of the control group averaged 4.97, but when acetaminophen 50 mg / kg and Nanten fruit extract 250 mg / kg were administered alone, the respective fever coefficients averaged 4.48 and 3.88, Both drugs showed antipyretic action (relative index: 0.903 and 0.782). The antipyretic effect is more strongly observed in the combined administration of these two drugs, and the relative index (0.530) is based on the product of the relative indices when each of them is administered alone (0.903 × 0.782 = 0.706). And a synergistic effect was observed.
[0019]
Production Example 1
Acetaminophen 900 mg, Nanten Real Dry Extract-30 (same as used in Example 1) 250 mg, lactose 218 mg, crystalline cellulose 180 mg, carmellose calcium 180 mg, hydroxypropylcellulose 54 mg were uniformly mixed in a stirring granulator. . The mixture was granulated by adding alcohol, dried with a fluidized bed granulator, granulated using a granulator, and then mixed with 18 mg of magnesium stearate to prepare granules for tableting. . This tableting tablet was tableted into 200 mg tablets using a 8.0 mm diameter punch.
[0020]
【The invention's effect】
Nanten extract is useful as an antipyretic because it has antipyretic action and is safe with few side effects.
[Brief description of the drawings]
FIG. 1 is a graph showing the antipyretic effect of Nanten extract and ibuprofen.
FIG. 2 is a diagram showing the antipyretic effect of Nanten fruit extract and acetaminophen.

Claims (2)

  An antipyretic agent containing Nanten extract and acetaminophen as active ingredients. Southern extract, according to claim 1 Symbol placement antipyretics a southern berry extract.

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