JP4136143B2 - Lipolysis accelerator and slimming skin cosmetics - Google Patents

Description

【０００８】
（但し、式中Ｒは水素原子、単糖類もしくは少糖類の残基、又は炭素数２〜２０のアシル基である。）及び下記一般式（２）
【０００９】
【化４】

【００１０】
（但し、式中Ｒは水素原子、単糖類もしくは少糖類の残基、又は炭素数２〜２０のアシル基である。）が、上記作用を有し、脂肪組織に蓄積された脂肪の分解を促進し、肥満の抑制、又は肥満体質の改善に有効であることを見出し、本発明を完成した。
【００１１】
すなわち、本発明は、下記一般式（１）
【００１２】
【化５】

【００１３】
（但し、式中Ｒは水素原子、単糖類もしくは少糖類の残基、又は炭素数２〜２０のアシル基である。）及び下記一般式（２）
【００１４】
【化６】

【００１５】
（但し、式中Ｒは水素原子、単糖類もしくは少糖類の残基、又は炭素数２〜２０のアシル基である。）の一種、又は二種以上を含有する脂肪分解促進剤にある。また、本発明は、これらの脂肪分解促進剤を含有する痩身用皮膚化粧料にある。
【００１６】
【発明の実施の形態】
以下、本発明の実施の形態に関し、詳説する。本発明に用いられる化合物の中には、香料成分やメラニン生成抑制剤としての用途について提案している物質も含まれるが（特開平７-１７９３２８号公報、特開平１０-２６５３２５号公報）、それらが脂肪分解促進作用を有していることは何ら記載も示唆もなされていない。
【００１７】
本発明に用いる前記一般式（１）で表される化合物のうち、Ｒが単糖類又は少等類の残基のものは、いわゆる配糖体であり、市販されているものも多くあり容易に入手することができる。また、前記公報等に記載されている公知の方法で容易に合成することもできる。例えば、糖類と４−（ｐ−ヒドロキシフェニル）−２−ブタノンとを酸類の存在下に反応させることにより容易に合成できる。また従来公知のＫｏｅｎｉｇｓ−Ｋｎｏｒｒ反応等を用いることにより、β−体のみを合成することも可能である［Chem.ber.,34,957(1901)］。さらに、カラムクロマト等の手段を用いてこれらの配糖体を精製することもできる。尚、ここで残基とは、糖においてヘミアセタール性水酸基の水素を除いた残り部分を指す。
【００１８】
ここで少糖類とは、二糖類から六糖類迄を指し、具体的には、ラクトース、マルトース、シュークロース、セロビオース、イソマルトース、エピラクトース等の二糖類、ラフィノース、ゲンチアノース、メレチトース、マルトトリオース、セロトリオース、マンニノトリオース等の三糖類、スタキオース等の四糖類等を挙げることができる。また、単糖類としては、グルコース、ガラクトース、マンノース、ラムノース、キシロース、リボース、アラビノース、グルコサミン、ガラクトサミン等を挙げることができる。
【００１９】
本発明に用いる前記一般式（１）で表される化合物のうち、Ｒが炭素数２〜２０のアシル基のものは、フェノール化合物のアシル化として既に公知の方法を用いて得ることができる。例えば、ピリジン中において４−（ｐ−ヒドロキシフェニル）−２−ブタノンと酸クロライドとを反応させることにより、容易に得ることができる。尚、アシル基としては、内部に不飽和結合を有するものでも問題無く、また芳香環を有していてもよい。また、アミノ基等の官能基を有するものであってもかまわない。具体的には、プロピオニル、ブチリル、イソブチリル、バレリル、ヘキサノイル、ラウロイル、パルミトイル、オレオイル等を挙げることができる。
【００２０】
本発明に用いる前記一般式（２）で表される化合物も、４−（ｐ−ヒドロキシフェニル）−２−ブタノンの替りにジンゲロンを用いて上記同様にして得ることができる。
【００２１】
また、合成以外にも前記一般式（１）又は（２）で表される化合物を含有する植物から適当な溶媒によって抽出し、必要により公知の方法で濃縮や乾固して用いることもできる。
【００２２】
前記一般式（１）又は（２）で表される化合物は、脂肪分解促進剤として、一種又は二種以上を併用することができる。また、痩身用皮膚化粧料に用いる場合、配合量は痩身用皮膚化粧料の形態によっても種々異なり一概に規定できるものではないが、例えば、該化粧料中に０．００１〜２０重量％配合するのが好ましい。０．００１重量％未満では本発明の効果を奏しない場合があり、２０重量％を越えて配合しても、配合量に見合った効果が得られない場合がある。
【００２３】
本発明の痩身用皮膚化粧料には、必須成分である上記化合物の他に通常の皮膚化粧料において使用される、油分、顔料、界面活性剤、保湿剤、紫外線吸収剤、抗炎症剤、殺菌剤、防腐剤、色素等の他に、ブトパミン、イソプロテレノール等のβアドレナリン作用興奮剤、ヨヒンビン、エルゴトキシン等のα２アドレナリン作用抑制剤、テオフィリン、カフェイン等のキサンチン誘導体、ミルリノン、アムリノン等のビピリジン誘導体等、肥満の抑制又は防止作用を有する公知物質等を配合することができる。
【００２４】
本発明の脂肪分解促進剤は、例えば、食品、経口投与薬、皮膚化粧料等に配合することができ、また痩身用皮膚化粧料の剤型は特に限定されるものではなく、皮膚塗布用、浴用、洗浄用等のクリーム、乳液、ジェル、スティック、シート、パップ、粉末、液体、顆粒等とすることができる。
【００２５】
【実施例】
以下、本発明を実施例、比較例に基づき、詳説する。尚、脂肪分解促進効果の評価として、下記の脂肪分解試験、皮下脂肪分解試験にて評価した。尚、ラズベリーケトン及びジンゲロンは市販のものを用いた。それ以外の誘導体は前記の合成方法により得たものを用いた。
【００２６】
［脂肪分解試験法］
ロッドベルの方法〔Ｒｏｄｂｅｌｌ，Ｍ．，Ｊ．Ｂｉｏｌ．Ｃｈｅｍ．，２３９，３７５（１９６４）〕により、ウィスター系雄性ラット（体重１５０〜２００ｇ）の副睾丸脂肪組織からコラゲナーゼ溶液を用いて遊離脂肪細胞を調製した。被験物濃度が１００μg ／mlとなるよう調製した牛血清アルブミン及びノルエピネフリン（最終濃度０．０５μｇ／ｍｌ）を含むハンクス緩衝液中に上記細胞を加え、３７℃にて１時間反応した。遊離した脂肪酸を抽出し、銅試薬及び発色試薬により脂肪酸量を定量した。
【００２７】
脂肪分解促進率（％）＝［Ａ／Ｂ］×１００
Ａ：被験物添加時の脂肪酸量
Ｂ：コントロール（被験物無添加）の脂肪酸量
【００２８】
［皮下脂肪分解試験法］
ウィスター系ラット（雄、７〜９週齢）の腹部を刈毛後、同部皮膚を皮下脂肪組織とともに摘出し、直径２ｃｍのフランツ型拡散セルに装着する。角質層側の上部セルに皮膚化粧料０．５ｇを均一に塗布し、皮下脂肪組織側の下部セルにｐＨ７．２リン酸緩衝生理食塩水を満たす。セルを３７℃に保ち、６時間放置後、下部セルより緩衝溶液を採取し、溶液中に遊離したグリセロール量を酵素法（ベーリンガー・マンハイム社製 Ｆ−キット；グリセロール）にて測定する。尚、測定は５回行いその平均値で示す。
【００２９】
実施例１〜４、比較例１
各種脂肪分解促進剤について、上記の脂肪分解試験にて評価した結果を以下に示す。
【００３０】

【００３１】
実施例１〜４の脂肪分解促進剤は、脂肪分解促進率が比較例１及び２に比べはるかに高く脂肪分解促進作用が高いことが明らかにされた。
【００３２】
実施例５〜７、比較例３（ジェル状痩身用皮膚化粧料）
以下に示す組成で、常法によりＡ、Ｂ各成分を個別に混合溶解後、Ｂ成分をＡ成分に添加し攪拌することにより、ジェル状痩身用皮膚化粧料を調製した。
【００３３】

【００３４】
上記ジェル状痩身用皮膚化粧料について、前記の皮下脂肪分解試験にて評価した結果を以下に示す。
【００３５】

【００３６】
実施例８〜１０、比較例４（ローション状痩身用皮膚化粧料）
以下に示す組成で、常法によりＡ、Ｂ各成分を個別に混合溶解後、Ｂ成分をＡ成分に添加し攪拌することにより、ローション状痩身用皮膚化粧料を常法により調製した。。
【００３７】

【００３８】
上記ローション状痩身用皮膚化粧料について、前記の皮下脂肪分解試験にて評価した結果を以下に示す。
【００３９】

【００４０】
以上から明らかなように、実施例５〜１０は、皮下脂肪分解試験において脂肪分解物である遊離グリセロール量が比較例と比して格段に多く、皮下脂肪分解を促進することが判った。
【００４１】
【発明の効果】
本発明は、全身あるいは局所の脂肪組織を減少させ、肥満の抑制又は防止、肥満体質の改善に有効な脂肪分解促進剤、及び該効果を有する痩身用皮膚化粧料を提供できることは明らかである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a lipolysis accelerator effective for improving obesity constitution by promoting reduction of systemic or local adipose tissue, or suppressing or preventing obesity by preventing increase of the tissue, and the promotion of lipolysis The present invention relates to a slimming skin cosmetic containing an agent.
[0002]
[Prior art]
Fat in the body is a product of excess energy consumed compared to energy consumed, accumulated as neutral fat in white fat cells. Obesity with a large accumulation as body fat is not only cosmetically unfavorable, but also causes various diseases such as arteriosclerosis. Recently, obesity due to overeating, lack of exercise, stress, and the like has increased, but on the other hand, women tend to crave a slim, firm body in terms of appearance. In addition, accumulation of subcutaneous fat and the like is not preferable from the viewpoint of health, and it is an important problem to reduce or prevent the accumulation of subcutaneous fat and the like.
[0003]
On the other hand, capsaicins contained in capsicum and the like as substances that have anti-obesity action bind to albumin in the blood, secrete hormones that promote adrenal metabolism, and act on liver and fat cells to activate energy metabolism. (Kazuo Iwai and Nobuji Nakatani, food function of spice ingredients, page 97, 1989). However, since capsaicins have strong irritation, there is a problem that their use and use amount are limited. For this reason, various approaches using oral drugs such as appetite suppressants, dietary restrictions and exercise have been made, but the lipolysis promoter and slimming skin cosmetics that have a satisfactory effect of suppressing or reducing subcutaneous fat, etc. It was not found.
[0004]
[Problems to be solved by the invention]
Therefore, the present invention provides a lipolysis promoter and slimming skin effective for improving obesity by promoting reduction of systemic or local adipose tissue, or for inhibiting or preventing obesity by preventing increase of the tissue. The purpose is to provide cosmetics.
[0005]
[Means for Solving the Problems]
In order to achieve the above object, it is difficult for the present inventors to eliminate the fat cells once accumulated, and it is a fast way to make the fat cells as small as possible. For this purpose, oil droplets in the fat can be decomposed. I thought that it was necessary, and researched earnestly. Oil droplets are broken down by enzymes (phospholipase C) just like proteins. However, the oil droplets are covered with a phospholipid membrane that repels water, and the enzyme in the water mass called a parcel around the oil droplets cannot be accessed. On the other hand, by activating the sympathetic nerve by exercising, lipolytic hormone is secreted and fat decomposition is promoted. At this time, the hormone can promote lipolysis by removing the phospholipid membrane and increasing the affinity between the enzyme and the oil droplets. We thought that it was necessary to find a substance that has the function of increasing the affinity between oil droplets and enzymes as well as this hormone.
[0006]
Therefore, the present inventors have studied substances that act on fat cells and promote lipolysis, and as a result, the following general formula (1)
[0007]
[Chemical 3]

[0008]
(Wherein R is a hydrogen atom, a monosaccharide or oligosaccharide residue, or an acyl group having 2 to 20 carbon atoms) and the following general formula (2)
[0009]
[Formula 4]

[0010]
(Wherein R is a hydrogen atom, a residue of a monosaccharide or oligosaccharide, or an acyl group having 2 to 20 carbon atoms) has the above-described action, and decomposes fat accumulated in adipose tissue. The present invention was completed by finding that it is effective for suppressing obesity or improving obesity constitution.
[0011]
That is, the present invention provides the following general formula (1)
[0012]
[Chemical formula 5]

[0013]
(Wherein R is a hydrogen atom, a monosaccharide or oligosaccharide residue, or an acyl group having 2 to 20 carbon atoms) and the following general formula (2)
[0014]
[Chemical 6]

[0015]
(In the formula, R is a hydrogen atom, a monosaccharide or oligosaccharide residue, or an acyl group having 2 to 20 carbon atoms), or a lipolysis accelerator containing two or more kinds. Moreover, this invention exists in the skin cosmetics for slimming containing these lipolysis promoters.
[0016]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, embodiments of the present invention will be described in detail. The compounds used in the present invention include substances proposed for use as perfume ingredients and melanin production inhibitors (Japanese Patent Laid-Open Nos. 7-179328 and 10-265325). There is no description or suggestion that has an action to promote lipolysis.
[0017]
Among the compounds represented by the general formula (1) used in the present invention, those in which R is a monosaccharide or a minor residue are so-called glycosides, and there are many commercially available ones that can be easily used. Can be obtained. Moreover, it can also be easily synthesized by a known method described in the above publication. For example, it can be easily synthesized by reacting a saccharide with 4- (p-hydroxyphenyl) -2-butanone in the presence of acids. It is also possible to synthesize only the β-isomer by using a conventionally known Koenigs-Knorr reaction or the like [Chem. Ber., 34, 957 (1901)]. Furthermore, these glycosides can be purified using means such as column chromatography. Here, the term “residue” refers to the remaining part of the sugar excluding the hydrogen of the hemiacetal hydroxyl group.
[0018]
Here, oligosaccharides refer to disaccharides to hexasaccharides, specifically, disaccharides such as lactose, maltose, sucrose, cellobiose, isomaltose, and epilactose, raffinose, gentianose, meletitose, maltotriose, Examples thereof include trisaccharides such as cellotriose and manninotriose, and tetrasaccharides such as stachyose. Examples of monosaccharides include glucose, galactose, mannose, rhamnose, xylose, ribose, arabinose, glucosamine, galactosamine and the like.
[0019]
Among the compounds represented by the general formula (1) used in the present invention, those in which R is an acyl group having 2 to 20 carbon atoms can be obtained by a method already known as acylation of a phenol compound. For example, it can be easily obtained by reacting 4- (p-hydroxyphenyl) -2-butanone and acid chloride in pyridine. In addition, as an acyl group, even if it has an unsaturated bond inside, there is no problem and you may have an aromatic ring. Moreover, you may have functional groups, such as an amino group. Specific examples include propionyl, butyryl, isobutyryl, valeryl, hexanoyl, lauroyl, palmitoyl, oleoyl and the like.
[0020]
The compound represented by the general formula (2) used in the present invention can also be obtained in the same manner as described above using gingerone instead of 4- (p-hydroxyphenyl) -2-butanone.
[0021]
In addition to the synthesis, it can be extracted from a plant containing the compound represented by the general formula (1) or (2) with an appropriate solvent, and if necessary, concentrated or dried by a known method.
[0022]
The compound represented by the general formula (1) or (2) can be used alone or in combination of two or more as a lipolysis accelerator. In addition, when used for slimming skin cosmetics, the blending amount varies depending on the form of the slimming skin cosmetics and cannot be specified unconditionally. For example, 0.001 to 20% by weight is blended in the cosmetic. Is preferred. If the amount is less than 0.001% by weight, the effect of the present invention may not be achieved. Even if the amount exceeds 20% by weight, the effect corresponding to the amount may not be obtained.
[0023]
The slimming skin cosmetics of the present invention include oils, pigments, surfactants, moisturizers, ultraviolet absorbers, anti-inflammatory agents, bactericides used in ordinary skin cosmetics in addition to the above-mentioned compounds that are essential components. In addition to agents, preservatives, pigments, etc., β-adrenergic stimulants such as butopamine, isoproterenol, α2-adrenergic inhibitors such as yohimbine, ergotoxin, xanthine derivatives such as theophylline, caffeine, milrinone, amrinone, etc. Known substances or the like having an action of suppressing or preventing obesity such as bipyridine derivatives can be blended.
[0024]
The lipolysis promoter of the present invention can be blended in, for example, foods, orally administered drugs, skin cosmetics, etc., and the dosage form of slimming skin cosmetics is not particularly limited. Creams, emulsions, gels, sticks, sheets, packs, powders, liquids, granules and the like for bathing and washing can be used.
[0025]
【Example】
Hereinafter, the present invention will be described in detail based on examples and comparative examples. In addition, as an evaluation of the lipolysis promotion effect, the following lipolysis test and subcutaneous lipolysis test were evaluated. Commercially available raspberry ketone and gingerone were used. Other derivatives were obtained by the above synthesis method.
[0026]
[Lipolysis test method]
Rodbell method [Rodbell, M .; , J .; Biol. Chem. , 239, 375 (1964)], free adipocytes were prepared from a testicular adipose tissue of Wistar male rats (body weight 150 to 200 g) using a collagenase solution. The cells were added to Hank's buffer containing bovine serum albumin and norepinephrine (final concentration 0.05 μg / ml) prepared so that the test substance concentration was 100 μg / ml, and reacted at 37 ° C. for 1 hour. The liberated fatty acid was extracted, and the amount of fatty acid was quantified with a copper reagent and a coloring reagent.
[0027]
Lipolysis promotion rate (%) = [A / B] × 100
A: Fatty acid amount at the time of test substance addition B: Fatty acid amount of control (no test substance added)
[Subcutaneous lipolysis test method]
After shaving the abdomen of Wistar rats (male, 7-9 weeks old), the skin of the part is removed together with the subcutaneous adipose tissue and attached to a 2 cm diameter Franz diffusion cell. Apply 0.5 g of skin cosmetic material uniformly to the upper cell on the stratum corneum side, and fill the lower cell on the subcutaneous adipose tissue side with pH 7.2 phosphate buffered saline. The cell is kept at 37 ° C. and allowed to stand for 6 hours, and then a buffer solution is collected from the lower cell, and the amount of glycerol released in the solution is measured by an enzymatic method (F-kit; Boehringer Mannheim F-Glycer). In addition, the measurement is performed 5 times and the average value is shown.
[0029]
Examples 1-4, Comparative Example 1
About the various lipolysis promoter, the result evaluated in said lipolysis test is shown below.
[0030]

[0031]
It was clarified that the lipolysis promoters of Examples 1 to 4 have a much higher lipolysis promotion rate than Comparative Examples 1 and 2, and a high lipolysis promoting action.
[0032]
Examples 5 to 7, Comparative Example 3 (Skin cosmetic for gel-like slimming)
A gel-like slimming skin cosmetic was prepared by mixing and dissolving each of the A and B components individually in a conventional manner and adding the B component to the A component and stirring.
[0033]

[0034]
About the said gel-form slimming skin cosmetics, the result evaluated in the said subcutaneous lipolysis test is shown below.
[0035]

[0036]
Examples 8-10, comparative example 4 (skin cosmetic for lotion-like slimming)
With the composition shown below, each component A and B was separately mixed and dissolved by a conventional method, and then the B component was added to the A component and stirred to prepare a lotion-shaped slimming skin cosmetic by a conventional method. .
[0037]

[0038]
The results of evaluating the lotion-like slimming skin cosmetic in the subcutaneous lipolysis test are shown below.
[0039]

[0040]
As is clear from the above, Examples 5 to 10 showed that the amount of free glycerol, which is a lipolysis product, was much higher in the subcutaneous lipolysis test than in the comparative examples, and it was found that subcutaneous lipolysis was promoted.
[0041]
【The invention's effect】
It is clear that the present invention can provide a lipolysis accelerator effective for reducing systemic or local adipose tissue, suppressing or preventing obesity, improving obesity constitution, and slimming skin cosmetics having the effect.

Claims (3)

The following general formula (1)

Wherein R is a hydrogen atom, a monosaccharide, a disaccharide, a trisaccharide or a tetrasaccharide residue, or an acyl group having 2 to 20 carbon atoms.   A slimming skin cosmetic comprising the lipolysis promoter according to claim 1.   A slimming skin cosmetic containing 0.001 to 20% by weight of the lipolysis promoter according to claim 1.