KR20060134057A - Antiaging composition - Google Patents

Abstract

The object of the present invention is to provide a composition which is effective in retarding or preventing the development of energy decrease, appearance change, etc. of humans and animals due to aging, and is highly safe even with a long period of taking. The present invention relates to an antiaging composition which comprises reduced coenzyme Q as an active ingredient. By feeding mice which develop the aging symptom early (aging-accelerated model mice) with a feed containing reduced coenzyme Q10 for a long period of time, aging process was prevented and retarded. Furthermore, aging-accelerated model mice fed with reduced coenzyme Q10 for a long period of time showed no toxic symptom, thus it was found that the antiaging composition comprising a composition containing said substance can be made into a safe antiaging composition capable of being taken for a long period of time.

Description

Anti-aging composition {ANTIAGING COMPOSITION}

The present invention relates to a composition capable of inhibiting or delaying aging.

Anti-aging effects have been considered in two aspects so far. One is the effect on external aging, ie skin aging, especially including wrinkles and blemishes. Such effects may include effects such as skin elasticity and moisture retention. Primarily, external preparations such as cosmetics have claimed this effect, and some products have proven effective in humans. Another aspect is the effect on body aging except skin aging. As products effective in inhibiting aging of the body, supplements based on antioxidant activity may be mentioned. However, when examined in detail, the anti-aging effects claimed by these supplements are only inferred from the effects obtained in vitro and are not demonstrated from the effects obtained in vivo. Among the in vitro effects seen by such supplements are, for example, the effect of inhibiting lipid peroxidation, the effect of inhibiting the formation of hemocysteine, whose content in the body may increase with age. However, no direct relationship between this in vitro test and in vivo efficacy has been identified. With regard to the above-mentioned anti-aging cosmetics and the like, the fact that the effect of oxidative stress on skin aging is largely reliable, as exemplified by the fact that ultraviolet irradiation causes skin deterioration. However, with regard to aging of the living body, it is thought that only such an antioxidant activity is very insufficient. Although an anti-aging agent for skin containing ubiquinone (oxidized coenzyme Q) has been disclosed (Japanese Patent Application Publication No. 2002-513746), this document does not have any description or suggestion of reduced coenzyme Q. In addition, methods of treating memory disorders due to aging, including administering carnitine with coenzyme Q and / or creatine, if necessary, are known in the art (Japanese Patent Publication No. 2003-513039). However, carnitine is an essential ingredient in this method. This document does not mention anything about reduced coenzyme Q ₁₀ or anti-aging, nor does it contain any detailed reports of anti-psychotic effects.

Oxidized coenzyme Q ₁₀ is sold as an anti-aging supplement. In fact, however, its efficacy has never been exemplified and is only inferred from the antioxidant activity of coenzyme Q ₁₀ . In addition, reduced coenzyme Q ₁₀ has never been commercialized due to its easily oxidized nature, and no actual anti-aging effect is known in the art, such as oxidized coenzyme Q ₁₀ .

It is an object of the present invention to provide a substance or composition that can inhibit (delay) aging.

As a result of extensive studies to solve the above-mentioned problems, the present inventors have found for the first time that the reduced coenzyme Q ₁₀ has a significant anti-aging (delay) effect.

Therefore, the present invention relates to an anti-aging composition comprising reduced coenzyme Q represented by the following formula (1) as an active ingredient.

Wherein n represents an integer of 1 to 12.

Coenzyme Q is an essential component widely distributed in organisms from bacteria to mammals, and it is known to occur as a component of the electron transport system of the mitochondria among cells in vivo. Coenzyme Q acts as a transfer component in the electron transfer system by repeating oxidation and reduction in the mitochondria. It is also known that reduced coenzyme Q exhibits antioxidant activity. In humans, coenzyme Q ₁₀ has 10 repeating units in the side chain of coenzyme Q is the main component. As mentioned above, reduced coenzyme Q ₁₀ exhibits antioxidant activity in vitro, while oxidized coenzyme does not exhibit antioxidant activity. However, oxidized coenzyme Q ₁₀ is known to be converted to reduced form by reductase in vivo.

An important feature of coenzyme Q ₁₀ is its high stability. Long-term toxicity studies in rats showed no toxic effects when coenzyme Q ₁₀ was administered daily at 52 mg / kg / day for 52 weeks (KD Williams et al., J. Agric. Food Chem. 47, 3756-). 3763, 1999). The dose of 1,200 mg / kg / day corresponds to 60 g / day when converted based on human (50 kg body weight). Since the usual dosage of coenzyme Q ₁₀ used as health food in Europe and the United States is 100-300 mg / day, it is clear that coenzyme Q ₁₀ is a very stable supplement.

Coenzyme Q is reduced coenzyme Q represented by the following formula (1); And / or oxidized coenzyme Q represented by the following formula (2).

<Formula 1>

Wherein n represents an integer of 1 to 12.

Wherein n represents an integer of 1 to 12.

The method for obtaining the oxidized coenzyme Q and the reduced coenzyme Q is not particularly limited. Examples of methods that can be used include obtaining coenzyme Q in a conventional manner such as synthesis, fermentation or extraction from a natural source, and then oxidizing coenzyme Q portion and reduced coenzyme Q portion in an eluate by chromatography. It includes a method comprising the step of concentrating. If oxidized coenzyme Q is required, methods known in the art can be used. If reduced coenzyme Q is required, a conventional reducing agent such as sodium borohydride or sodium dithionite (sodium hydrosulfite) is added to the coenzyme Q as needed and the coenzyme Q is reduced in a conventional manner to reduce the form. Coenzymes can be obtained, which are then concentrated by chromatography. It can be obtained by a method comprising reacting a high purity coenzyme Q product, which also has reduced coenzyme Q, with a reducing agent as mentioned above (see, eg, Carpino, LA et al, 1989, J. Org. Chem. 54, 3303-3310).

The anti-aging composition of the present invention is a composition comprising reduced coenzyme Q as an active ingredient.

As long as the anti-aging composition of the present invention contains reduced coenzyme Q as an active ingredient, coenzyme Q is not particularly limited, but may be made only in reduced form or may be a mixture with an oxidized form.

Coenzyme Q that can be used in the practice of the present invention can be any of those having 1 to 12 repeating units (n in the formula) in the side chain, as shown in formula (1) or (2) above. However, among these, one having ten side chain repeating units (n being 10 in the above formulas (1) and (2)), that is, coenzyme Q ₁₀ is particularly preferably used.

When coenzyme Q is a mixture of reduced and oxidized forms, the content of reduced coenzyme Q is preferably at least 20% by weight, more preferably at least 40% by weight, even more preferably at least 50% by weight relative to the total amount of coenzyme Q. In general, the upper limit is preferably 99.5% by weight or less, but may be 95% by weight or less.

In the antiaging composition of the present invention, the reduced coenzyme Q content is preferably 0.001 to 99% by weight, more preferably 0.01 to 99% by weight, even more preferably 0.1 to 50% by weight based on the total composition.

In addition to coenzyme Q, the anti-aging composition of the present invention may contain various additives that are acceptable in view of medical or food hygiene. When the anti-aging composition of the present invention is used as a measure for various diseases, it can be used in combination with a medicament for related diseases.

The above-mentioned additives are not particularly limited but include, for example, excipients / diluents, disintegrants, lubricants, binders, coatings, colorants, anticoagulants, absorption accelerators, dissolution aids, stabilizers, health food ingredients, nutritional supplements (supplements) ), And the like.

Excipients / diluents include, but are not particularly limited to, white sugar, lactose, glucose, corn starch, mannitol, crystalline cellulose, calcium phosphate, calcium sulfate, and the like.

Although it does not specifically limit as a disintegrating agent, For example, starch, agar, calcium citrate, calcium carbonate, sodium hydrogencarbonate, dextrin, crystalline cellulose, carboxymethylcellulose, tragacanth, etc. are included.

Lubricants include, but are not particularly limited to, talc, magnesium stearate, polyethylene glycol, silica, hydrogenated vegetable oils and the like.

Although it does not specifically limit as a binder, For example, ethylcellulose, methylcellulose, hydroxypropyl methylcellulose, tragacanth, shellac, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, poly Methacrylic acid, sorbitol and the like.

Although it does not specifically limit as a coating agent, For example, gum arabic, oppadry, vinegar, castor wax, carboxyvinyl polymer, camelos, hydrous silicon dioxide, magnesium silicate, vinyl acetate resin, stearic acid, cetanol, a hydride Oxypropylmethylcellulose and the like.

Although it does not specifically limit as a coloring agent, For example, what was authorized to add to a drug and / or food, etc. can be used.

The anti-agglomeration agent is not particularly limited but includes, for example, stearic acid, talc, hard silicic anhydride, hydrous silicon dioxide and the like.

Absorption accelerators include, but are not particularly limited to, higher alcohols, higher fatty acids, surfactants such as glycerol fatty acid esters, and the like.

The dissolution aid is not particularly limited but includes, for example, organic acids such as fumaric acid, succinic acid, malic acid and the like.

Although it does not specifically limit as a stabilizer, For example, benzoic acid, sodium benzoate, ethyl parahydroxy benzoate, etc. are included.

The health food ingredients are not particularly limited, but for example, herbal medicines (e.g., Yuryeongtang (medicinal herb extracts for treating gastrointestinal disorders, etc.), Ongyeongtang (medicinal herb extracts to warm the body), warm hearing sound (blood circulation Herbal extracts for palpation, Hwanggigunjungtang (Astragalus Membranaseus)Astragalus membranaceusExtract), Hwangyeonhaedoktang (medicinal herb extract to reduce heat, inflammation, etc.), Hwangyeontang (Cofftis Chinensis)Coptis chinensisExtracts), Galgeuntang (Pueraria Radix (Puerariae radixExtract), Gamiguibi-tang (medicinal herb extract for treating anemia, insomnia, neurosis, etc.), Kamisoyosan (a herbal extract for treating physiological impurity and menopausal disorders), Gamgdaejo-tang (night terrors, seizures, etc.) Medicinal Herb Extracts), Gilkyung-tang (Platicodone Grandiflorum)Platycodon grandiflorumExtracts, etc.), Guibi-tang (medicinal herb extracts for treating anemia, insomnia, etc.), Gumi-Bin-Lang-Tang (9 kinds of herbal medicines, for example, the sub-globosa of the ribitis or Chinesis strain)Livistona chinesis var. subglobosaExtract), Hyungaeyeon Gyotang (a herbal extract for treating chronic sinusitis, acne, etc.), Cinnamon Gajakdae Rhubarb Tang (a herbal extract for treating gastrointestinal disorders), Cinnamon Gajaktang (Cinnamo cortex (Cinnamomi cortex), Extracts of peony, etc.), cinnamon dragon bone gultang (Cinnamo cortex (Cinnamomi cortex), Australian gas (Ostrea gigasExtracts such as), Gyeji-tang (Cinnamo cortex (Cinnamomi cortexExtracts, etc.), Gyeji Ginseng Bath (Cinnamo cortex (Cinnamomi cortex), Extracts such as ginseng), Gyeji Bokryeong-hwan (Cinnamo cortex (Cinnamomi cortex), Paria Cocos (Poria cocosExtracts), Gyebi-tang (medicinal herb extracts for the treatment of indigestion, diarrhea, etc.), Hyangsosan (Cyperus rotunders (Cyperus rotundusExtracts), Ohho-tang (medicinal herb extract for treating colds, asthma, etc.), Ohji-san (herbal extract for blood circulation and water circulation), Woo Cha Hyun-hwan (medicinal herb extract for improving physical function), orim Acid (medicinal herb extract for the treatment of urination, pain, urination, etc.)Bupleurum chinense), Jahogaryonggolgultang (Buffleum Chinens)Bupleurum chinense), Australian gas (Ostrea gigasExtracts such as), Jaho Cinnamon Health Bath (Buffleum Chinens)Bupleurum chinense), Cinnamon cortex (Cinnamomi cortex), Ginger Ver.Zingiber officinaleExtracts), Jahogyejitang (Buffleum Chinens)Bupleurum chinense), Cinnamon cortex (Cinnamomi cortexExtracts, etc.), Jahocheonggantang (Buffleum Chinens)Bupleurum chinense), Scutellaria Baicalensis George (Scutellaria baicalensis GeorgiExtracts), Jabaktang (Buffleum Chinens)Bupleurum chinense), Scutellaria Baicalensis George (Scutellaria baicalensis Georgi), Pinelia Ternate (Pinellia ternateExtracts, etc.), Jaryeong-tang (medicinal herb extract for reducing inflammation, improving water circulation, etc.), Sanjoi-tang (Jipipus Yuyuba (Zizyphus jujubaExtracts), Jaumganghwatang (medicinal herb extract for the treatment of coughs), Sasan (Buppleum Chinens)Bupleurum chinenseExtracts, etc.), Sagunja-tang (medicinal herb extract for improving gastrointestinal function), Samul-tang (4 kinds of herbal medicines, for example Angelica Synenssis (Angelica sinensisExtracts), Jagamcho-tang (medicinal herb extracts to treat palpitations, short breaths, etc.), Peonyamcho-tang (Paeonia lactiflora (Paeonia lactiflora) And glycyrrhiza uralensis (Glycyrrhiza uralensisExtracts, etc.), Sipjeondaebotang (medicinal herb extract for rejuvenation and rejuvenation), Simmi-Paddogtang (10 kinds of herbal extracts used for dermatitis, etc.), Sogeonjung-tang (medicinal herb extract for improving gastrointestinal function), Sojaho-tang ( Liver herb extract), Socheongryongtang (medicinal herb extract for allergic rhinitis, asthma, etc.), Sopoong acid (herbal extract for the treatment of eczema), Sinyicheongwaetang (magnolia cobus (Magnolia kobusExtracts), mystery bath (Ephedra sinica (Ephedra sinicaExtracts, etc.), Sinmutang (a herbal extract to warm the body to improve body function), Cheongsangbangpungtang (a herbal extract for treating acne), Cheongseoikgi-tang (a herbal extract for summer bosin), Cheongsimyeon consonant (urination disorder) Herbal extracts for treatment, etc.), Cheongheungtang (Magnolia praecosis Shima (Magnolia praecocissimaExtracts, etc.), Sokyeong Byeolheoltang (medicinal herb extract to reduce neuralgia, back pain, etc.), Rhubarb persimmon tea (Reum TanguticumRheum tanguticum) And glycyrrhiza uralensis (Glycyrrhiza uralensisExtract), Rhubarb dandanpitang (Reum Tanguticum (Rheum tanguticum), Paeonia Supruticosa (Paeonia suffruticosaExtract), Daegunjungtang (medicinal herb extract to reduce stomach pain, etc.), Daejahotang (Buffleum Chinens)Bupleurum chinense), Scutellaria Baicalensis George (Scutellaria baicalensis GeorgiExtracts from the back), Daeja Hotang Rhubarb (Buffleum Chinens)Bupleurum chinense), Scutellaria Baicalensis George (Scutellaria baicalensis Georgi), Pinelia Ternate (Pinellia ternateExtracts), Daeseunggi-tang (medicinal herb extract for the treatment of constipation), Pungbang-tang (Ledebouriella ceceloides (Ledebouriella seseloidesExtracts, etc.), cheetah (one herbal extract for the treatment of bruises), Jowiseunggi-tang (herbal extract for intestinal relaxation, etc.), Saengsan Mountain (Uncaria Lihinchophyla (Uncaria rhynchophyllaExtracts), Jang Ongtang (medicinal herb extract for lower abdominal pain), Jeonyeongtang (Polyporous Umbelatus)Polyporus umbellatusExtracts, etc.), yeongnyeongtang hapsamultang (polyporous umbellathus (Polyporus umbellatusExtracts), Tongdosan (medicinal herb extract for treating physiological impurities, dysmenorrhea, etc.), Dokukseunggi-tang (medicinal herb extract for treating constipation, menstrual impurities, etc.) Herbal Extracts for Treatment), Dangwi-GunjungtangAngelica sinensis), Cinnamon cortex (Cinnamomi Cortex), Paeonia lactiflora (Paeonia lactifloraExtracts such as), Angelica peony acid (Angelica sinensis (Angelica sinensis), Paeonia lactiflora (Paeonia lactifloraExtracts such as), Dangguitang (angelica sinensis (Angelica sinensisExtracts, etc.), Ijintang (sickness, narcotic extract for reducing vomiting), goddess acid (medicinal herb extract for the treatment of flashes, dizziness, etc.), ginseng tang (extracts such as ginseng), ginseng nutrition bath (ginseng, Astragalus membran) Lanaeus (Astragalus membranaceusExtracts), Baeongsansantang (medicinal herb extract for treating skin tumors, etc.), McMoonDongtang (Oopiogon Japonicus)Ophipopogon japonicusExtracts such as), palmi hwanghwan (8 herbal drugs, for example, Lehmannia glutinosa (Rehmannia glutinosaCrude extracts, etc.), Banhahubaktang (Pinelia Ternate (Pinellia ternate), Magnolia Officinalis (Magnolia officinalisExtracts such as), Banhasasimtang (Pinelia Ternate (Pinellia ternateExtracts such as), Baekhogainsamtang (extracts such as gypsum), Bokryeongum (Poria cocos (Poria cocosExtracts such as), Bokryeong Yinhapbanhahubaktang (a herbal extract for reducing morning sickness during pregnancy), Pyungwisan (a herbal extract for treating heavy stomach, etc.), Bangiwanggi-tang (Aristolochia Panchi (Aristolochia fangchi), Astragalus Membranaseus (Astragalus membranaceusExtracts such as), windproof tonic acid (Ledebouriella ceceloides (Ledebouriella seseloidesExtracts), Bojungikgi-tang (medicinal herb extract for improving gastrointestinal function), Mahwang-tang (Ephedra sinica (Ephedra sinicaExtracts), ephedra sinica (Ephedra sinica (Ephedra sinica), Aconitum Karmichaeri (Aconitum carmichaeriExtracts), Mahanegamseoktang (Ephedra sinica (Ephedra sinica), Prunus Armeniaca (Prunus armeniacaExtracts such as), Mazainhwan (cannabis sativa (Cannabis sativaExtracts, etc.), disulfide (Cocolus trilobus (Cocculus trilobusExtracts, etc.), jingan acid (medicinal herb extract for reducing nervous excitement), jingan acid with subcutaneous skin extract (medicinal herb extract for reducing nervous excitability), army jar tang (medicinal herb extract for reducing plants, etc.), lactic acid ( Herbal extracts for toothache reduction, etc.Gentiana scabraExtracts, etc.), inspirational Gangmi Sinhaintang (medicinal herb extract for cough control and neck cleaning), Yumimihwan (extract of six herbal medicines, used for improving body function, etc.), tea leaves (for example, green tea, Brown tea, matcha tea, green tea, roasted tea, roasted tea, jasmine tea, oolong tea, black tea, black tea, flower tea, green tea, white tea, etc., herbs (e.g. Italian parsley, elecampane, olives, oregano, cardoon) , Chamomile, Curry Plant, Catnip, Caraway, Christmas Rose, Crimson Clover, Cornflower, Common Marlow, Salad Burnet, Santolina, Cinnamon, Jasmine, Stevia, Sage, Linden (Lime), Scented Geranium, Red Pepper St.-John's-wort), Soap, Round, Thyme, Tange, Chereville, Chaive, Watercress, Nutmeg, Basil, Honeysuckle, Hyssop, Flax, Fennel, Foxglobe, Black hollyhock, French marigold, Bethany, Heliotrope, Bergamot, Hemp Agrimoni, Ruta, Pho Marigold, borage, white hound, silver plum, mullein, marjoram, mint, horsefly, lavender, lady's bedstrow, lemongrass, lemon verbena, lemon balm, rose, rosemary, rocket, wild strawberry, wild pansy, Forget-me-not, etc.), pycnogenol, flavangenol, propolis, ginseng leaves, royal jelly, carnitine, mushrooms, chlorophyll juice, extracts from these, and the like.

Nutritional supplements include, but are not particularly limited to, amino acids, metal ions, proteins, sugars, fatty acids, yeast extracts, plant extracts, fish meat extracts, fruits, fruit extracts, and the like.

The anti-aging composition of the present invention may contain other antioxidants.

As antioxidants, for example, citric acid, citric acid derivatives, vitamin C, vitamin C derivatives, lycopene, vitamin A, carotenoids, vitamin B, vitamin B derivatives, flavonoids, polyphenols, glutathione, selenium, sodium thiosulfate, vitamin E, Vitamin E Derivatives, Pyrroloquinoline Quinone, Pyrroloquinoline Quinone Derivatives, Peroxy Dismutase (SOD), Glutathione Peroxidase, Glutathione-S-Transferase, Glutathione Reductase, Catalase, Ascorbic Acid Peroxidase and Theirs Mixtures and the like.

The method for producing an anti-aging composition of the present invention includes mixing the reduced coenzyme represented by the formula (1) with an acceptable additive.

Thus, the above-mentioned anti-aging composition is added, mixed, sprayed, containing, or conjugated to, for example, the above-mentioned obtained reduced coenzyme Q, as necessary, the above-mentioned additives, antioxidants and the like. It can be prepared as. In addition, according to a preferred dosage form to be mentioned below, various additives, solvents, bases, etc., which are acceptable as pharmaceutical and / or food additives, to reduced coenzyme Q are added and the resulting mixture is especially granulated, coated, microencapsulated The above-mentioned anti-aging composition can be obtained through a process of preparing into various suitable dosage forms through, encapsulation, incorporation, emulsification, suspension, and the like.

The dosage form of the anti-aging composition of the present invention may be a liquid or a solid. As the method of administration, various methods can be used, such as oral administration, injection, intranasal administration, administration in the form of eye drops or suppositories, or ingestion of coenzyme Q-containing foodstuffs. In terms of dosage, etc., oral administration is generally considered the most effective method. If oral administration is difficult, the compositions of the present invention may be administered by other routes besides oral administration, without other problems. For example, preferred methods of administration for patients or the elderly who are difficult to orally consume nutrients include, but are not limited to, suppository forms, external preparations, and the like.

In the case of oral administration, for example, the dosage of the anti-aging composition of the present invention shown in terms of the amount of coenzyme Q is preferably 30 to 1,200 mg, more preferably 50 to 800 mg, even more preferably 100 per person per day. To 300 mg.

The anti-aging composition of the present invention may inhibit or delay aging of humans and / or animals.

As used herein, “aging” refers to, for example, slowing behavior, such as reduced activity or lowered passiveness, spinal curvature, hair loss, corneal haze, eye and / or ear periphery inflammation, and the like.

Administration of the anti-aging composition of the present invention may delay or ameliorate the onset of such aging-related symptoms.

In the evaluation of this anti-aging effect, for example, aging-accelerated model mice can be used as an in vivo evaluation model. This mouse is a model mouse that was found and bred at the Kyoto University in Japan in early and remarkably aging state. This mouse exhibits an aging state very similar to that of humans and is a useful model animal for in vivo testing of anti-aging effects.

The method for inhibiting aging in an animal according to the present invention includes administering the anti-aging composition to a target animal.

Animals include mammals, fish, birds, reptiles, insects and the like. Preferred as animals are mammals, such as humans.

"Administration" herein means to include local, intestinal, for example oral or rectal, or parenteral administration. As the route of administration, oral administration is preferred.

The reduced coenzyme Q-containing compositions of the present invention exhibit excellent effects on inhibiting or delaying aging.

1 is a graph showing the increase in aging scores in aging-accelerated model mice taking reduced coenzyme Q ₁₀ . The coordinates represent the degree of aging score. Data are expressed as mean ± standard deviation (n = 10). Significant tests were performed in the Student t test mode. * Table shows that there was a significant difference of 5% error range for the control group, ** Table shows a significant difference of 1% error range for the control group. The horizontal axis represents the age of the mice in months.

2 is taking the oxidized coenzyme Q ₁₀ age-a graph showing the aging score increase in an accelerated model mice. The coordinates represent the degree of aging score. Data are expressed as mean ± standard deviation (n = 10). Significant tests were performed in the Student t test mode. * Table shows that there was a significant difference of 5% error range for the control group, ** Table shows a significant difference of 1% error range for the control group. The horizontal axis represents the age of the mice in months.

The following examples illustrate the invention in more detail. However, these examples do not limit the scope of the present invention in any way.

Purity and reduced coenzyme Q ₁₀ / (reduced coenzyme Q ₁₀ + oxidized coenzyme Q ₁₀ ) ratio (weight ratio) were measured by HPLC analysis as follows.

(HPLC analysis condition)

Column: Symmetry C18 (from Waters), 250 mm (length), 4.6 mm (inner diameter); Mobile phase: C ₂ H ₅ 0H: CH ₃ 0H = 4: 3 (v: v); Detection wavelength: 210 nm; Flow rate: 1 ml / min; Retention time for reduced coenzyme Q ₁₀ : 9.1 minutes, Retention time for oxidized coenzyme Q ₁₀ : 13.3 minutes

Preparation Example 1 Preparation of Reduced Coenzyme Q ₁₀

100 g of oxidized coenzyme Q ₁₀ (purity 99.4%) and 60 g of L-ascorbic acid were added to 1,000 g of ethanol, and the mixture was caused to undergo a reduction reaction with stirring at 78 ° C. After 30 hours, the mixture was cooled to 50 ° C. and 330 g of ethanol and 70 g of water were added while maintaining the temperature. The ethanol solution (containing 100 g of reduced coenzyme Q ₁₀ ) was cooled to 2 ° C. at a cooling rate of 10 ° C./hour while stirring to obtain a white slurry. The resulting slurry was filtered under reduced pressure, the wet crystals were washed sequentially with cold ethanol, cooled water and cooled ethanol (the temperature of the cooled solvent used was 2 ° C.), and the wet crystals were further dried under reduced pressure. (20 to 40 ℃, 1 to 30 mmHg) to obtain a reduced coenzyme Q ₁₀ 97 g, as white dry crystals. All experiments except those dried under reduced pressure were carried out under a nitrogen atmosphere.

Preparation Example 2 Preparation of Reduced Coenzyme Q ₁₀

The oxidized coenzyme Q ₁₀ 100 g was dissolved in 1,000 g of heptane at 25 ℃. While stirring the solution, an aqueous solution prepared by dissolving 100 g of sodium dithionite (purity 75% or more) as a reducing agent was gradually added to 1,000 ml of water to allow a reduction reaction to proceed at 25 ° C. and pH 4 to 6. After 2 hours, the aqueous phase was removed from the reaction mixture and the heptane phase was washed six times with 1,000 g of deaerated saturated aqueous chloride solution. The heptane phase was solvent substituted under reduced pressure to prepare a 7% (w / w) solution of reduced coenzyme Q ₁₀ in ethanol at 50 ° C. 50 g of water was added to the ethanol solution, and the mixture was cooled to 2 ° C at a cooling rate of 10 ° C / hr while stirring to allow crystals to precipitate. All experiments were performed under a nitrogen atmosphere. The slurry thus obtained was filtered under reduced pressure and wet crystals were washed sequentially with cooled ethanol, cooled water and cooled ethanol (the temperature of the cooled solvent used for washing was 2 ° C). And dried under reduced pressure to give additional crystals to obtain a wet (20 to 40 ℃, 1 to 30 mmHg) reduced coenzyme Q ₁₀ 97 g (oxidized coenzyme Q ₁₀ contained about 1%) as white dry crystals.

Example 1 Aging Inhibition (Delay) Effects in Aging-Accelerated Model Mice

Aged-accelerated model rats (SAMP1, 3 week old female) reduced coenzyme Q ₁₀ obtained in Preparation Example 1 The (oxidized coenzyme Q ₁₀ from about 1% content), and so as to free access to 0.2%, containing a feed (CE-2, nuclease (CLEA) jeopaen, Inc., Ltd.), according to the aging scores presented to the aging of each rat Quantification over time. The reduced coenzyme Q ₁₀ dose estimated from food consumption and animal body weight was about 150-250 mg / kg / day. The control group received only food (CE-2, CLEA Japan, Inc.).

The aging-accelerated model rats used are the model rats found and raised in Kyoto University that show an early, markedly aging state. These mice exhibit an aging state very similar to humans and are useful model animals for in vivo testing of anti-aging effects. The aging scoring system used is a scoring system established by the SAM Study Group. Therefore, each animal representing each of the eleven items as follows is given a score of 0-4.

1: reduced activity (navigation behavior), 2: passiveness (escape from bullying), 3: hair loss, 4: hair stiffness, 5: hair loss, 6: skin ulcers, 7: eye lesions (eyelids) Saline and peri-aspiral erosion), 8: corneal haze, 9: corneal ulcers, 10: cataracts, 11: increased vertebral curves before and after. A score of 0 was given based on symptoms found in a group of young rats about 3 months of age. Thus, high scores indicate that aging has progressed further.

The results are shown in FIG. As can be seen in Figure 1, as a result of taking reduced coenzyme Q ₁₀ it was possible to significantly prevent the increase in aging score.

(Comparative Example 1)

The same procedure as in Example 1 was conducted except that oxidized coenzyme Q ₁₀ was used instead of reduced coenzyme Q ₁₀ . The dose of oxidized coenzyme Q ₁₀ estimated from food consumption and animal body weight is about 150-250 mg / kg / day, which is almost the same as the dose of reduced coenzyme Q ₁₀ . The results are shown in Table 2. As a result of taking the oxidized coenzyme Q _10, the increase in the aging degree was somewhat suppressed, but the anti-aging effect was weaker than the reduced coenzyme Q ₁₀ .

(Formulation Example 1) Powder

Reduced coenzyme Q ₁₀ (containing about 1% of oxidized coenzyme Q ₁₀ ) was dissolved in propanol, absorbed onto microcrystalline cellulose, and dried under reduced pressure. This was mixed with corn starch in a nitrogen flow to obtain a powder.

9.9 parts by weight of reduced coenzyme Q ₁₀

Oxidized Coenzyme Q ₁₀ 0.1 parts by weight

40 parts by weight of microcrystalline cellulose

55 parts by weight of corn starch

(Formulation Example 2) Capsule

Using the materials detailed below, powders were prepared in the same manner as in Formulation Example 1. This powder was filled in gelatin capsules in a conventional manner. The filled capsules were sealed and packaged under nitrogen atmosphere and stored in the refrigerator.

Reduced coenzyme Q ₁₀ 19.8 parts by weight

0.2 parts by weight of oxidized coenzyme Q ₁₀

40 parts by weight of microcrystalline cellulose

20 parts by weight of corn starch

Lactose 65 parts by weight

Magnesium stearate 3 parts by weight

2 parts by weight of polyvinylpyrrolidone

Formulation Example 3 Soft Capsule

Corn oil was warmed to 50 ° C. Thereto was added reduced coenzyme Q ₁₀ (containing about 1% of oxidized coenzyme Q ₁₀ ) melted at the same temperature for dissolution. The solution was filled into soft capsules in a conventional manner.

Reduced coenzyme Q ₁₀ 49.5 parts by weight

Oxidized coenzyme Q ₁₀ 0.5 parts by weight

350 parts by weight of corn oil

(Formulation Example 4) Tablet

Reduced coenzyme Q ₁₀ (containing about 1% of oxidized coenzyme Q ₁₀ ) was dissolved in propanol, absorbed into microcrystalline cellulose and dried under reduced pressure. It was mixed with corn starch, lactose, carboxymethylcellulose calcium and magnesium stearate in a nitrogen atmosphere, then an aqueous polyvinylpyrrolidone aqueous solution was added as a binder to the resulting mixture, and the whole mixture was granulated in a conventional manner. To this granule product, talc was added as a lubricant and mixed, and the resulting mixture was made into a tablet. Tablets were packaged in a nitrogen atmosphere and stored in a refrigerator.

Reduced coenzyme Q ₁₀ 19.8 parts by weight

0.2 parts by weight of oxidized coenzyme Q ₁₀

25 parts by weight of corn starch

Lactose 15 parts by weight

Carboxymethyl cellulose calcium 10 parts by weight

40 parts by weight of microcrystalline cellulose

5 parts by weight of polyvinylpyrrolidone

Magnesium stearate 3 parts by weight

10 parts by weight of talc

The reduced coenzyme Q-containing compositions of the present invention exhibit excellent effects on inhibiting or delaying aging.

Claims (7)

An anti-aging composition comprising reduced coenzyme Q represented by the following formula (1) as an active ingredient. <Formula 1>

Wherein n represents an integer of 1 to 12. The anti-aging composition according to claim 1, wherein the reduced coenzyme Q is reduced coenzyme Q ₁₀ . The anti-aging composition according to claim 1, which contains an oxidized coenzyme Q represented by the following formula (2). <Formula 2>

Wherein n is an integer from 1 to 12. The composition for anti-aging according to claim 3, wherein the oxidized coenzyme Q is oxidized coenzyme Q ₁₀ . The anti-aging composition according to any one of claims 1 to 4, wherein the content of reduced coenzyme Q is 0.001 to 99% by weight. A method for inhibiting aging of an animal, comprising administering the anti-aging composition according to any one of claims 1 to 5 to a target animal. A method for producing a composition for anti-aging comprising mixing a reduced coenzyme Q represented by the following formula (1) with an acceptable additive. <Formula 1>

Wherein n is an integer from 1 to 12.

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