JP4698167B2 - Alzheimer's disease prevention and treatment - Google Patents

Description

  The present invention relates to a preventive / therapeutic agent for Alzheimer's disease.

  Alzheimer's disease, which is considered to be the biggest risk factor in the aging society, is a serious social problem. Compared to cerebrovascular dementia triggered by cerebral infarction, cerebral thrombus, etc., Alzheimer's dementia develops gently without any abnormalities in the internal medicine, and slowly from the first stage to the third stage. However, it will surely proceed. Alzheimer's disease includes familial ones that are dominantly inherited and sporadic ones that are not, and the latter accounts for more than 90% of the total.

Recently, with regard to the cause of the onset, accumulation of β-amyloid in the brain triggers a pathological cascade leading to Alzheimer's disease, which causes intracellular protein accumulation, inflammatory response, and neuronal dysfunction Studies on the identification of pathogenic genes in familial Alzheimer's disease and the prevention and treatment of sporadic Alzheimer's disease by promoting β-amyloid degradation activity are underway. For example, angiotensin converting enzyme is known as a component that suppresses the accumulation of β-amyloid in the brain (Patent Document 1).
Many other studies have been conducted, but until now, no absolute prevention / treatment method for Alzheimer's disease has been found, and development results are awaited.

On the other hand, the effectiveness of plant extracts from various plants, such as antibacterial action, blood circulation promoting action, antiallergic action, moisturizing action, etc., has been studied from various fields such as external preparations for skin, cosmetics, and pharmaceuticals.
As an example, the plant of the genus Coleoptera is a perennial plant belonging to the family Aceraceae, which has been confirmed from Himalaya to China. The effectiveness of the plant extract is about the effect of promoting hair growth (Patent Document 2), Prevention and treatment (Patent Document 3), prevention and treatment of Clostridium perfringens infection in domestic animals and poultry (Patent Document 4), and the like are known. However, the application to preventive and therapeutic agents for Alzheimer's disease has not been studied so far.
JP 2001-316287 A JP 2003-221313 A JP-A-1-172334 JP-A-1-172341

  An object of the present invention is to provide a drug for preventing Alzheimer's disease and treating it while suppressing the progression of Alzheimer's disease.

The inventors have conducted research on plant extracts, and as a result, surprisingly, the effects of certain plants and their extracts are completely different from the effects known for each of them. It was found that neuronal cell death caused by introduction of a gene mutant can be suppressed.
Accordingly, the present invention contains the error Rukanpu les as an active ingredient, to Alzheimer's disease prophylactic or therapeutic agent.

  Kollen plant, Basicurmon plant, Catharanthus plant, Iris plant, Raspberry plant, Cotton plant, Gull plant, Gull plant, Cactiaceae plant, Keratostigma plant, Hiyos plant, Elcampure, Hasnohagiri, Muirapuama, and By applying one or more selected from the group consisting of wood vinegar as an active ingredient, neuronal cell death due to the introduction of a mutant of the Alzheimer's disease-causing gene can be suppressed. Therefore, the usefulness can be expected as a prophylactic agent for preventing the onset of Alzheimer's disease for healthy individuals and as a therapeutic agent for suppressing the progression of disease states for Alzheimer's disease patients.

  Alzheimer's disease preventive / therapeutic agent according to the present invention is a plant belonging to the genus Kollen, Baciclemon, Periwinkle, Iris plant, Raspberry plant, Cotton plant, Gull genus plant, Gull genus plant, Cactiaceae plant, Keratostigma genus plant 1 type or 2 types or more selected from the plant of the genus Hyos, Ercampure, Hasunohagiri, Muirapuama, and wood vinegar as an active ingredient. These plants, plant extracts, or wood vinegar liquid contain a great many kinds of components that cannot be analyzed, and these act comprehensively to obtain the effects of the present invention. Guessed.

The plant of the genus Coleoptera is a perennial belonging to the family Aceraceae, and two types have been confirmed from the Himalayas to China. From the viewpoint of Alzheimer's disease prevention / treatment effect, it is preferable to use a rhizome of Kouren ( Picrorhiza kurrooa Royle) or Tibetan Kouren ( Picrorhiza scrophulariiflora Pennell).

  The plant belonging to the genus Baciclemon is a perennial herb belonging to the family Oleander, and about 30 species are known from North America to Mexico, the Eurasian continent, and the like. Regarding its effectiveness, lipase inhibitory effect, α-glucosidase inhibitory effect, α-amylase inhibitory effect and the like are known, but application to prophylactic / therapeutic agents for Alzheimer's disease has not been studied so far.

From the viewpoint of Alzheimer's disease prevention and therapeutic effects, it is preferable to use the whole plant or leaves Yanron (Apocynum venetum L.), or Oshorosou (Apocynum venetum L. var. Basikurumon ( Hara) Hara).

  Periwinkle is a perennial belonging to the oleander family and is a general term for a group of plants that exist over several genera. As its effectiveness, antitumor activity, tyrosinase activity inhibitory action and the like are known, but application to prophylactic / therapeutic agents for Alzheimer's disease has not been studied so far.

Periwinkle ( Catharanthus roseus (L.) Don; Vinca rosea L.; Lochnera rosea (L.) Reichb.), Which is usually cultivated domestically, as well as periwinkle ( Vinca major L.) cultivated mainly in Europe, For example, Vinva minor L. can be used. As the site to be used, it is preferable to use whole grass from the viewpoint of the effect of preventing and treating Alzheimer's disease.

  Iris plants are perennials belonging to the Iridaceae family, and about 250 species are widely distributed in the northern hemisphere temperate zone and subarctic zone. Regarding its effectiveness, it has been widely studied mainly for skin external preparations, and hydrogen peroxide scavenging action, stratum corneum peeling promoting action, immune defense stimulating component, antibacterial action, ceramide production promoting action, etc. are known, The application to the preventive / therapeutic agent for Alzheimer's disease has not been studied so far.

Iris florentiana L.; Iris pallida , Iris fulva Ker-Gawl., German iris ( Iris germanica L.), Himeshaga ( Iris ) gracilipes A. Gray, Shaga ( Iris japonica Thunb.), Iris confusa Sealy, Iris laevigata Fischer ( Iris versicolor L.), Black Iris ( Iris nigricans ), Kirisbu ( Iris pseudacorus L.), Iris rossi Baker, Iris sanguinea Hornem., Iris setosa Pall., Iris sibirica L., Iris tectorum Maxim .; Iris pallida Lam., Iris tenax Dougl), sickle mountain iris (iris thunbergii Lundst), Blue flag (iris versicolor L.), Spain iris (iris xiphium L.;.. iris boissieri), Ola Daayame (Iris tingitana;. Iris hollandica Hort ) , etc. are exemplified.
Among these genus plants, it is preferable to use black iris ( Iris nigricans ) or Dutch iris ( Iris tingitana ; Iris hollandica Hort.) In view of the effect. As a site to be used, it is preferable to use a rhizome or a corm.

  Rubus plants belong to the family Rosaceae and are distributed on all continents in the world. Fruits of the genus Rubus are often used for food, and their effectiveness is as follows: blood circulation promoting action, hyaluronic acid production promoting action, matrix metalloprotease activity inhibiting action, hyaluronidase activity inhibiting action, antiallergic action, suppression of Langerhans cell decrease Although its action and serine protease activity inhibitory action are known, application to prophylactic / therapeutic agents for Alzheimer's disease has not been studied so far.

Rubus genus plant is not particularly limited, such as wild species, cultivated species, blackberries ( Rubus ulmiformis ; Rubus laciniatus ; Rubus allegheniensis ; Rubus argutus ; Rubus frondosus Bigel.), Mountain blackberries ( Rubus allegheniensis Port.; Rubus nigrobaccus Bailey) , Chishima strawberry ( Rubus arcticus L.), Fuyu strawberry ( Rubus buergeri Miq.), European dauberry ( Rubus caesius L.), American Dauberry ( Rubus canadensis L .; Rubus flagellaris Willd.), Holomu strawberry ( Rubus chamaemorus L.), Rubus chingii Hu, Bear Strawberry ( Rubus crataegifolius Bunge), Oni Strawberry ( Rubus ellipticus Sm.; Rubus flavus Ham.), Yabusu Strawberry ( Rubus fruticosus L.), Hibusyu Strawberry ( Rubus hayata-koidzumii Naruhashi), Kusa Strawberry ( Rubus hirsutus Thunb.; Rubus thunbergii Sieb. et Zucc.), European raspberry ( Rubus idaeus L.; Rubus strigosus Michx;. Rubus xanthocarpus;.. Rubus ursinus) and the giant European raspberry (Rubus idaeus L. subsp its variants vulgatus), the United States Miki strawberry (Rubus idaeus L. subsp strigosus), Siberian raspberry (Rubus idaeus L. subsp. Melanolasia Focke), Sakhalinki strawberry ( Rubus idaeus L. subsp. Sachalinensis Leveille), Kamchatka strawberry ( Rubus idaeus L. subsp. Sibiricus ), rose strawberry ( Rubus illecebrosus Focke), Evergreen ( Rubus laciniatus Willd.) And its Oregon Ever Glynn is a variant, saw Reference Evergreen, loganberry (Rubus l oganobaccus Bailey) and diploid thereof Nigaichigo (Rubus microphyllus L. f;.. Rubus incisus Thunb), Nan iodine raspberry (Rubus moluccanus L.), Raspberry ( Rubus neglectus Peck.; Rubus niveus Thunb.; Rubus albescens Roxb.), Blackberry strawberry ( Rubus occidentalis L.), Momijiichigo (Rubus palmatus L.), native raspberry (Rubus parvifolius L.), Tsurukogane strawberry (Rubus pedatus JE Smith.), wine raspberry (Rubus phoenicolasius Maxim.), Barabbas raspberry (Rubus rosaefolius Smith.) and variants thereof in a Tokin'ibara (. Rubus sieboldii Bl) (. Rubus spectabilis Pursh) (Rubus rosaefolius Smith var coronarius Smith;...; Rubus commersonii Poir. Rubus illecebrosus Focke forma tokinibara Hara), Hourokuichigo, salmon berry, Rubus Trifidus (Rubus trifidus Thunb .), Pacific Dowberry ( Rubus ursinus Cham. Et Schlecht.), Safflower Strawberry ( Rubus vernus Focke) and the like.
Among these Raspberry genus plants, it is particularly preferable to use holomui strawberry from the viewpoint of the effect of preventing and treating Alzheimer's disease. The site to be used when using the genus Rubus is not particularly limited, such as whole grass, leaves, flowers, fruits and the like, but it is preferable to use fruits from the viewpoint of the effect and availability of raw materials.

  Cotton plants widely cultivated as fiber crops and used as oils are used as cottonseed oil, and are known to inhibit IgE production, inhibit testosterone-5α-reductase activity, etc., but prevent and treat Alzheimer's disease The application to the agent has not been studied so far.

As the cotton genus plant, cultivated cotton ( Gossypium herbaceum L.) can be used. The site to be used is not particularly limited, such as whole grass, leaves, stems, flowers, seeds, seed hair, roots and root barks, but roots are preferably used from the viewpoint of Alzheimer's disease prevention and treatment effects.

  Both the gull genus plant and the giant gull genus plant are dicotyledonous plants that belong to the genus Musci. As for the effectiveness of the genus Cairoidae, AIDS treatment active ingredients, antibacterial and antifungal activities, etc. are known, but application to prophylactic / therapeutic agents for Alzheimer's disease has not been studied.

Vincetoxicum is not particularly restricted but includes plants, Funabarasou (Cynamchum atratum Bunge; Vincetoxicum hirundiaria) , Ikema (.. Cynanchum caudatum (Miq) Maxim), Byakubi (Cynanchum versicolor Bunge), Suzusaiko (Cynanchum paniculatum (Bunge) Kitagawa) , Koikema ( Cynanchum wilfordii (Maxim.) Hemsl.) And the like. It is preferable from the viewpoint of the Alzheimer's disease prevention and treatment effect that the use site of these gull genus plants is whole grass or roots including roots, particularly rhizomes.
There are no particular limitations on the plant species of the genus Gull, such as Tylophora aristolochioides Miq., Tylophora japonica Miq, Tylophora floribunda Miq., Tylophora indica (Burtt. Is exemplified. From the viewpoint of the Alzheimer's disease prevention / treatment effect, it is preferable to use the whole plant including roots or roots as the site of use of the plant of the genus Euglena.

  Cactaceae plants are succulent plants with various thorns, and their effectiveness is known to have moisturizing action, fibroblast growth promoting action, antiviral action, hair growth / hair growth action, etc., but prevention of Alzheimer's disease・ The application to therapeutic agents has not been studied so far.

Although it is not limited as a cactiaceae plant, it is particularly possible to use one or more selected from the group consisting of Takeyumaru ( Echinocereus engelmanii ), Silver Sand Maru ( Mammillaria runhyonii ), and Ryumaru ( Escobaria emskoeteriana ) From the viewpoint of the prevention / treatment effect of Alzheimer's disease, it is preferable. As a use site | part, the whole grass containing a root or the above-ground site | part can be used.

Keratostigma is a plant belonging to the family Pinaceae and is widely cultivated as a horticultural variety. Application examples in the pharmaceutical and food fields are not particularly known.
Is not particularly restricted but includes keratoring stigma plants of the genus, Plumbago beetle (Ceratostigma plumbaginoides), keratosulfate stigma (Ceratostigma willmottianum), such as Bhutan Plumbago (Ceratostigma griffithii) are exemplified. The use site is not particularly limited, and whole grass, leaves, flowers, seeds and the like can be used.

  The genus Hyos is a plant belonging to the family Solanaceae, and alkaloids contained in leaves have been applied as anticholinergic agents, but their application to Alzheimer's disease preventive / therapeutic agents has not been studied so far.

The Hyos plant is not particularly limited, and examples thereof include Hyos ( Hyoscyamus niger L.) and its mutants such as wax ( Hyoscyamus niger L. var. Chinensis Makino) and micron ( Hyoscyamus aureus ). From the viewpoint of Alzheimer's disease prevention / treatment effect, it is preferable to use leaves as the use site of these genus plants.

Hercampure (Hercampure; Gentianella alborosea (Gilg)) is a dicotyledon of the Gentianella Gentianaceae and is a perennial that grows in mountains and alpine areas. Although known as a Peruvian herb and reported to be effective in lifestyle-related diseases, its application to Alzheimer's disease prevention and treatment agents has not been studied.
From the viewpoint of preventing and treating Alzheimer's disease, it is preferable to use the above-mentioned site or leaf as the site of use of Elcampure.

Hasunahagiri ( Hernodia peltata ) is an evergreen tree of the genus Hasnohagiri, which is widely planted on the coasts of Okinawa to tropical Asia, Australia, Africa and other places. Known as a foliage plant, its medicinal effects have not been studied so far.
From the viewpoint of the Alzheimer's disease prevention / treatment effect, bark is preferably used as the site for using Hasunohagiri.

Muirapuama ( Ptychopetalum olacoides ) is an Amazon rainforest and shrub native to northern Brazil. Indigenous tribes of the Amazon used as medicinal herbs in the old days, and now they are used as therapeutic agents for neuralgia, chronic rheumatism, paralysis, etc. in herbal medicine in the United States and Europe, but for application to Alzheimer's disease prevention and treatment, It has not been studied until.
As the use site of muirapuama, it is preferable to use roots and stems from the viewpoint of the effect of preventing and treating Alzheimer's disease.

  Wood vinegar is a liquid obtained by cooling the smoke that is emitted when burning trees into charcoal, and has been used for a long time among those engaged in charcoal burning and agriculture. Although blood circulation promoting action, antibacterial action, hair growth / hair growth promoting action and the like are known, application to Alzheimer's disease preventive / therapeutic agents has not been studied so far.

The plant for obtaining the wood vinegar used in the present invention is not particularly limited, but bamboo ( Phyllostachys heterocycla (Carr.) Mitf.) And its related plants, related plants, Pinus densiflora Sieb. Et Zucc. Using the genus plant, cypress ( Chamaecyparis obtusa (Sieb. Et Zucc.) Endl.) And its genus plant, eucalyptus ( Eucalyptus alba E.) and its genus plant, the effect of preventing and treating Alzheimer's disease It is preferable from the viewpoint.

As the above-mentioned plant, the collected raw plant can be used as it is or after being dried. In that case, an extract can also be used. As an extraction solvent for obtaining the extract, water; alcohols such as ethanol, methanol, isopropanol, isobutanol, n-hexanol, methylamyl alcohol, 2-ethylbutanol, n-octyl alcohol; glycerin, ethylene glycol, ethylene glycol monomethyl Polyhydric alcohols such as ether, ethylene glycol monoethyl ether, propylene glycol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, triethylene glycol, 1,3-butylene glycol, hexylene glycol or derivatives thereof; acetone, methyl ethyl ketone, methyl Ketones such as isobutyl ketone and methyl-n-propyl ketone; esters such as ethyl acetate and isopropyl acetate; Ether, isopropyl ether, ethers such as n- butyl ether; one selected from polar solvents such as, or two or more mixed solvent can be suitably used. Also, phosphate buffered saline can be used, and the type of extraction solvent is not particularly limited.
From the viewpoint of Alzheimer's disease prevention / treatment effect, it is preferable to use a polar solvent, and moreover, one or more kinds selected from the group consisting of methanol, ethanol, 1,3-butylene glycol, and water. It is preferable to use a mixed solvent, and it is particularly preferable to use water as the solvent.

  Examples of the extraction method include a method of extraction by immersion in a cooled or heated state at room temperature, a method of extraction using a distillation method such as steam distillation, a pressing method of squeezing from a raw plant to obtain an extract, etc. These arbitrary methods can be extracted alone or in combination of two or more.

  Although the ratio of the plant and the solvent in the extraction is not particularly limited, the solvent is preferably 0.5 to 1000 times by weight with respect to the plant 1, and particularly 0.5 to 100 wt. Double is preferred. The extraction temperature is convenient to be in the range from room temperature to the boiling point of the solvent under normal pressure, and the extraction time varies depending on the combination of the plant and solvent, the extraction temperature, etc. A range of 2 hours to 2 weeks is preferable.

  The plant extract thus obtained can be used as it is, but within the range that does not lose the Alzheimer's disease prevention / treatment effect of the present invention, purification operations such as deodorization, decolorization, and concentration are added. Alternatively, it may be used as a fraction using column chromatography or the like. These extracts, purified products, and fractions can be dried by removing the solvent from them, and can also be provided in a form solubilized in a solvent such as alcohol, or in the form of an emulsion. it can.

The agent for preventing and / or treating Alzheimer's disease according to the present invention contains the above-mentioned specific plant or its extract or wood vinegar as an active ingredient, and is generally used in combination with any pharmacologically acceptable pharmaceutical carrier. It is preferable to be in the form of a simple pharmaceutical preparation composition.
The dosage form is not particularly limited, but representative examples include solid preparations such as tablets, capsules, pills, powders, granules, and injections (solutions, suspensions, emulsions, etc.). . It can also be a suppository or a sublingual tablet. If necessary, it is also preferable to use a known coating method to form a sustained-release preparation, a multilayer tablet, a sugar-coated tablet, a gelatin-coated tablet, or the like. The injection may be used by mixing with commonly used replacement fluids such as glucose and amino acids. Alternatively, it can be provided as a dry product that should be liquid at the time of use.
The administration route may be any of oral administration, parenteral administration such as intravenous, subcutaneous, intramuscular, intraperitoneal administration, etc. in the case of an injection, and is preferably selected as appropriate according to the patient's age, medical condition and other conditions. .

The solid preparation is usually mixed with a preparation carrier used as an excipient, binder, lubricant, filler, disintegrant, bulking agent, or the like. Specific examples include lactose, sucrose, starch, glucose, dextrin, cyclodextrin, cellulose, methylcellulose, carboxymethylcellulose, polyethylene glycol, polyvinylpyrrolidone, gelatin, kaolin, talc, colloidal silica, and the like. Can be used singly or in combination of two or more depending on the preparation form. In liquid preparations, water for injection, ethanol, propylene glycol, macrogol, etc. are used as diluents, and suspending agents such as sodium lauryl sulfate, lecithin, benzalkonium chloride, polyvinyl alcohol; phosphates, acetic acid Buffering agents such as salts and citrates; isotonic agents such as sodium chloride and glycerin are preferably blended as necessary.
In addition, any known additive usually used in the pharmaceutical field such as an absorption accelerator, a colorant, a sweetener, an antiseptic, an antioxidant, a humectant, and an adsorbent can also be used.

  The amount of the active ingredient contained in the prophylactic / therapeutic agent is not particularly limited and is appropriately selected depending on the disease state, dosage form, etc., but is generally about 0.5% in the total pharmaceutical preparation composition. It is preferable to be about ˜50% by weight. The dosage or dosage is not particularly limited because it varies depending on the age, sex, weight, disease severity, etc. of the patient, but in general, the total amount of active ingredients is about 0 per day for adults. It is appropriate that the dose is about 1 to 1000 mg, and it is appropriate to divide once to several times a day (for example, 3 to 4 times).

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to these.
(Effects of extract of moss on nerve cell death)
In the following manner, the effect of inhibiting the death of nerve cells was examined. In order to eliminate the effects of cytotoxicity, tests were carried out using specific fractional components of the moss extract.

18 g of dried pulverized rhizomes were weighed and diluted to 180 mL with a diluent (mixed solution of 180 mL of methanol and 820 mL of 2% aqueous formic acid). Extraction was performed by sonication at room temperature for 30 minutes, and the extract was filtered through a 0.45 μm filter (manufactured by Millipore).
The obtained crude extract was fractionated under the following conditions using high performance liquid chromatography with a mass spectrometer, and a peak portion having a retention time of 7.7 minutes was collected. The solvent was removed from the obtained fraction components under reduced pressure, and the residue was dried with a freeze dryer to obtain 2.9 mg of a final dried product. From this, the content of the component of the said peak part in the dried pulverized material of Koryen rhizome was 0.016%.

(1) Equipment used (LC-MS) Waters
Binary Gradient Module 2996
Gradient
Sample Manager 2767
Photodiode Array Detector 2996
Micromass ZQ
(2) Preparative conditions HPLC
Analytical column: Xterra Prep MS C18, 5μm, φ19mm × 50mm (Lot T31351)
Mobile phase: 18:82 (v / v) mixture of methanol and 2% aqueous formic acid Mobile phase flow rate: 13.6 mL / min
Diluent flow rate: 1.2mL / min
Column temperature: Room temperature Injection volume: 1000 μL
Wavelength (PDA): 250-300nm
Fraction trigger: Mass (m / z = 166)
MS
Ionization mode: ES +
Mass (m / z): 167
Cappilary: 3.50kV
Cone: 25V
Desolvation Temperature ： 350 ℃

The inhibitory effect of neuronal cell death induced by transducing V642I-APP, which is a mutant of the Alzheimer's disease-causing gene, using F11 cells, which is a type of neuronal cell, Examination was based on the presence or absence. Specifically, F11 cells were seeded on a 6-well microplate so as to be 7.0 × 10 ⁴ cells per well. Using Hams F-12 medium supplemented with 18% fetal bovine serum, the cells were cultured at 37 ° C. for 24 hours in 5% carbon dioxide in a humidified atmosphere. Subsequently, after transfection with V642I-APP, the cells were cultured for 5 hours, and Korlen extract fractions 50, 100, and 200 μg / mL were added thereto, and the culture was further continued for 72 hours. It should be noted that cytotoxicity to F11 cells was not observed when the added amount of the extract of Koolen was 200 μg / mL or less.
A similar test was carried out using F11 cells transduced with Vector as a control. Cell mortality was calculated by the trypan blue method.
The results are shown in Table 1.

  As shown in Table 1, the cell mortality increased by about 40 points to 50.8% by introducing a mutant of the Alzheimer's disease causative gene. The cell death rate is 29.4% at 20 mL / mL, 20 points or more lower than that of the untreated cells. Furthermore, when the addition amount is 100 μg / mL, the cell death rate is 12.0%, which is the natural death level. Was almost 100%.

(Plant extract production example)
Each plant extract was prepared using the plants and solvents shown in Table 2. Extraction was performed by immersing 1 part by weight of a dried plant in a 20 times weight solvent at room temperature for 2 weeks, removing the solvent from the resulting extract and drying it.
Separately, fraction components (peak part with a retention time of 7.7 minutes) were separated from each of the obtained crude extracts in the same manner as described above, and the inhibitory effect on the neuronal cell death was examined. A significant inhibitory effect was shown.

(Formulation examples 1 to 15: tablets)
The following components (1) to (6) were uniformly mixed and compression-molded with a tableting machine to obtain one tablet of 200 mg. Take 3 to 10 tablets daily in several divided doses.
(1) Cornstarch 44.0 (wt%)
(2) Crystalline cellulose 40.0
(3) Carboxymethylcellulose calcium 5.0
(4) Silicic anhydride 0.5
(5) Magnesium stearate 0.5
(6) Each type of extracts 1 to 15 in Table 2 10.0

(Formulation Example 16: Lotion)
The following components (1) to (4) were sequentially added to (5) and dissolved uniformly to obtain a lotion agent.
(1) Ethanol 15.0 (wt%)
(2) Hydroxyethyl cellulose 0.1
(3) Methyl paraoxybenzoate 0.1
(4) Extract 1 in Table 2 0.5
(5) Purified water 84.3

(Formulation Example 17: Emulsion)
The following oil phase components (1) to (7) are mixed and heated to dissolve uniformly and kept at 70 ° C., while the water phase components (8) to (11) are mixed and heated to make it uniform. The temperature was set to 70 ° C. The oil phase component was gradually added to the aqueous phase component with stirring to emulsify, and cooled to obtain an emulsion.
(1) Stearic acid 0.2 (% by weight)
(2) Cetanol 1.5
(3) Vaseline 3.0
(4) Liquid paraffin 7.0
(5) Polyoxyethylene (10EO) monooleate 1.5
(6) Tocopherol acetate 0.2
(7) Extract 2 in Table 2 0.4
(8) Glycerin 5.0
(9) Methyl paraoxybenzoate 0.1
(10) Triethanolamine 0.1
(11) Purified water 81.0

(Formulation Example 18: Gel agent)
(2) is uniformly dissolved in the following component (5), (4) is dissolved and added to (1), then (3) is added to increase the viscosity, and (6) is added and mixed. A gel was obtained.
(1) Dipropylene glycol 10.0 (% by weight)
(2) Carboxyvinyl polymer 0.5
(3) Potassium hydroxide 0.1
(4) Methyl paraoxybenzoate 0.1
(5) Purified water 88.8
(6) Extract 3 in Table 2 0.5

(Formulation Example 19: Cream)
The oil phase components (1) to (8) below were mixed, dissolved and heated to 85 ° C, while the water phase components (9) to (11) were mixed, dissolved and heated to 85 ° C. Next, an oil phase component was added to this aqueous phase component and pre-emulsified, and then uniformly emulsified with a homomixer and cooled to obtain a cream.
(1) Beeswaw 6.0 (wt%)
(2) Cetanol 5.0
(3) Reduced lanolin 8.0
(4) Squalane 27.5
(5) Glyceryl fatty acid ester 4.0
(6) Lipophilic glyceryl monostearate 2.0
(7) Polyoxyethylene (20EO) sorbitan monolaurate 5.0
(8) Extract 4 in Table 2 0.5
(9) Propylene glycol 5.0
(10) Methyl paraoxybenzoate 0.1
(11) Purified water 36.9

(Formulation Example 20: Powder)
The powders of the following components (1) to (3) were mixed, pulverized by a pulverizer, and uniformly dispersed to obtain a powder.
(1) Magnesium aluminate silicate 95.3 (wt%)
(2) Carboxymethylcellulose calcium 4.5
(3) Extract 2 in Table 2 0.2

(Formulation Example 21: Candy)
The following components (1) and (2) were heated and mixed and homogenized, then cooled, components (3) and (4) were added at 70 ° C., mixed and homogenized, and molded to obtain a candy.
(1) Sucrose 60.0 (wt%)
(2) Minamata 39.5
(3) Extract 6 in Table 2 0.4
(4) Fragrance 0.1

(Formulation Example 22: Drink)
The following components (1) to (9) were sequentially added to (10) and homogenized to obtain a drink.
(1) Aminoethylsulfonic acid 1000mg
(2) Thiamine nitrate 10mg
(3) Riboflavin sodium phosphate 5mg
(4) Pyridoxine hydrochloride 10mg
(5) Anhydrous caffeine 50mg
(6) Citric acid 250mg
(7) D-sorbitol solution 8g
(8) Extract 1 of Table 2 10 mg
(9) Trace amount of perfume
(10) Amount of purified water to 100 mL

Claims (1)

  An Alzheimer's disease prophylactic / therapeutic agent containing Elcampure as an active ingredient.