[go: up one dir, main page]

WO2012063553A1 - Agent permettant de réduire le risque d'installation d'une maladie résultant d'une fluctuation de la pression sanguine au cours de la journée du type ne diminuant pas la nuit - Google Patents

Agent permettant de réduire le risque d'installation d'une maladie résultant d'une fluctuation de la pression sanguine au cours de la journée du type ne diminuant pas la nuit Download PDF

Info

Publication number
WO2012063553A1
WO2012063553A1 PCT/JP2011/071025 JP2011071025W WO2012063553A1 WO 2012063553 A1 WO2012063553 A1 WO 2012063553A1 JP 2011071025 W JP2011071025 W JP 2011071025W WO 2012063553 A1 WO2012063553 A1 WO 2012063553A1
Authority
WO
WIPO (PCT)
Prior art keywords
blood pressure
agent
hydrolyzate
dipper
risk
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2011/071025
Other languages
English (en)
Japanese (ja)
Inventor
高橋　真理
山本　直之
和久 山田
敏郎 池谷
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Asahi Soft Drinks Co Ltd
Original Assignee
Calpis Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Calpis Co Ltd filed Critical Calpis Co Ltd
Publication of WO2012063553A1 publication Critical patent/WO2012063553A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
    • A61K38/018—Hydrolysed proteins; Derivatives thereof from animals from milk
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention has a low blood pressure drop rate from night to early morning, and is generally a non-dipper, particularly a normal blood pressure person whose average blood pressure for 24 hours is normal.
  • the present invention relates to an agent capable of reducing the risk of developing various diseases caused by blood vessel troubles such as cardiovascular and cerebrovascular due to fluctuations.
  • hypertension is an important risk factor for many diseases such as cerebral infarction, myocardial infarction, myocardial ischemia, atherosclerosis, heart failure, stroke, coronary artery disease, peripheral vascular disease and the like. Therefore, many components having a blood pressure lowering effect have been found and used for hypertensive patients. For example, tripeptides such as Val Pro Pro and Ile Pro Pro, and casein hydrolysates containing these have angiotensin I converting enzyme inhibitory activity (ACEI activity) and are known to exhibit blood pressure lowering activity (See Patent Documents 1 and 2). The definition of such a hypertensive patient is not necessarily clear and varies depending on the measuring device, environment, etc.
  • ACEI activity angiotensin I converting enzyme inhibitory activity
  • the average of systolic blood pressure is generally In many cases, the target is 130 mmHg or more and the average diastolic blood pressure (DBP) is 80 mmHg or more (see Non-Patent Document 1).
  • Non-Patent Document 3 Although known (Non-Patent Document 3), there is no provision for clear classification criteria of the Dipper type and Non-dipper type at present.
  • non-dipper type human blood pressure diurnal variation is more cerebral infarction, myocardial infarction, myocardial ischemia, atherosclerosis, heart failure, stroke, coronary artery disease, peripheral vascular disease than Dipper type human Have been reported to tend to develop in the morning. It has been found that such a tendency is not only seen in the hypertension patient group, but also in the healthy person group whose normal blood pressure for 24 hours is normal.
  • antihypertensive agents to be administered to hypertensive patients are known, such as those having an action of lowering daytime blood pressure, and those that lower the overall daily blood pressure having a long-lasting effect.
  • those having an action of lowering daytime blood pressure and those that lower the overall daily blood pressure having a long-lasting effect.
  • it has the effect of bringing the average systolic blood pressure from the night to early morning of humans classified as non-dipper type closer to Dipper type. Little is known about the agents indicated.
  • An object of the present invention is to provide a blood pressure that is likely to develop in the morning for a specific non-dipper, particularly a normal blood pressure person whose average blood pressure is normal for 24 hours, with a low blood pressure drop rate from night to early morning.
  • the object is to provide an agent that can reduce the risk of developing diseases due to diurnal variation.
  • the brachial blood pressure was measured every 30 minutes with a portable 24-hour automatic sphygmomanometer, and the mean systolic blood pressure of 0:00 to 5:00 to the mean systolic blood pressure of 8:00 to 21:00.
  • diastolic blood pressure (DBP) is an agent that can be taken orally by humans with an average of less than 80 mmHg, and can reduce the risk of developing diseases due to blood pressure diurnal variation
  • Non-dipper-type blood pressure diurnal risk-reducing agent containing hydrolyzate containing Ile Pro Pro (IPP) and Val Pro Pro (VPP) or its concentrate obtained by hydrolyzing animal milk protein ( Hereinafter, it may be abbreviated as the mitigating agent of the present invention).
  • the upper systolic blood pressure was measured every 30 minutes with a portable 24-hour automatic blood pressure monitor, and the average systolic period of 0:00 to 5:00 with respect to the average systolic blood pressure of 8:00 to 21:00.
  • Non-dipper type humans whose blood pressure decrease rate is less than 10%, in particular, the upper arm blood pressure measured every 30 minutes with a portable 24-hour automatic sphygmomanometer is less than 130 mmHg, and the average DBP is less than 80 mmHg
  • the mean systolic period of 0:00 to 5:00 is measured with respect to the mean systolic blood pressure of 8:00 to 21:00, where the brachial blood pressure is measured every 30 minutes by a portable 24-hour automatic sphygmomanometer.
  • Non-dipper type humans whose blood pressure decrease rate is less than 10%, in particular, the upper arm blood pressure measured every 30 minutes with a portable 24-hour automatic sphygmomanometer is less than 130 mmHg, and the average DBP is less than 80 mmHg
  • a method for reducing the risk of developing disease due to blood pressure diurnal fluctuation by allowing a human to orally ingest a hydrolyzate containing IPP and VPP or a concentrate thereof obtained by hydrolyzing animal milk protein.
  • the alleviating agent of the present invention effectively reduces systolic blood pressure from night to early morning for humans having a specific non-dipper type blood pressure diurnal variation pattern, particularly healthy individuals with normal values of SBP and DBP.
  • the risk of developing many diseases such as cerebral infarction, myocardial infarction, myocardial ischemia, atherosclerosis, heart failure, stroke, coronary artery disease, peripheral vascular disease, etc. Can be expected to reduce.
  • the alleviation agent of the present invention has an average systolic period of 0:00 to 5:00 with respect to an average systolic blood pressure of 8:00 to 21:00, in which the upper arm blood pressure is measured every 30 minutes by a portable 24-hour automatic blood pressure monitor.
  • Non-dipper type humans whose blood pressure decrease rate is less than 10%, in particular, the upper arm blood pressure measured every 30 minutes with a portable 24-hour automatic sphygmomanometer is less than 130 mmHg, and the average DBP is less than 80 mmHg Targeting humans.
  • the latter human is a human who is not normally recognized as a hypertensive patient and does not require administration of a hypotensive agent even if it is a non-dipper type.
  • the non-dipper type group having a low blood pressure decrease rate at night or early morning has a higher risk of developing disease due to diurnal fluctuations in blood pressure than the Dipper type human group.
  • the mitigating agent of the present invention contains a hydrolyzate containing IPP and VPP or a concentrate thereof obtained by hydrolyzing animal milk protein.
  • animal milk proteins include cow milk, horse milk, sheep milk, goat milk, and skim milk, reduced milk, powdered milk, condensed milk, which are processed milk thereof, and milk or processed milk thereof is particularly preferable. It is already known that proteins contained in these include IPP sequences and VPP sequences.
  • the solid content concentration of animal milk is not particularly limited. For example, when skim milk is used, the non-fat milk solid content concentration is usually about 3 to 15% by mass, and 6 to 15% by weight is preferable in terms of productivity. .
  • the hydrolyzate used in the mitigating agent of the present invention preferably has a VPP content of 3 ⁇ g / ml or more, particularly 30 ⁇ g / ml to 60 ⁇ g / ml, so that IPP and VPP can be obtained from animal milk protein.
  • Is obtained by hydrolysis so that the content of IPP is 30 ⁇ g / ml to 40 ⁇ g / ml and IPP content is 2 ⁇ g / ml or more, in particular 20 ⁇ g / ml to 40 ⁇ g / ml, more preferably 20 ⁇ g / ml to 30 ⁇ g / ml. It is.
  • Examples of the hydrolysis method include a method of fermenting a raw material containing animal milk protein with lactic acid bacteria to obtain a fermented product (A), a method of enzymatically decomposing the raw material containing animal milk protein with an enzyme (B), and the above There is a method of obtaining a hydrolyzate by combining (A) and (B).
  • examples of lactic acid bacteria include lactic acid bacteria belonging to the genus Streptococcus, Lactococcus, Lactbacillus, Bifidobacteria, etc., and the Lactbacillus genus is preferred. Specific examples include Lactobacillus bulgaricus, Lactobacillus helveticus, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus fermentum. In particular, Lactobacillus helveticus excellent in IPP and VPP production efficiency can be preferably used.
  • CM4 strain National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center, 1-1-1 Higashi 1-1-1, Tsukuba City, Ibaraki Prefecture, Japan: FERM BP-6060, date of deposit 1997.15.15
  • CM4 strain This CM4 strain is registered under the above-mentioned deposit number in the Budapest Treaty concerning the international recognition of microbial deposits in patent procedures, and this strain has already been patented.
  • the lactic acid bacteria are preferably used as a sufficiently high starter that has been pre-cultured in advance.
  • the initial bacterial count is preferably about 10 5 to 10 9 cells / ml.
  • yeast can be used in combination during the fermentation.
  • the strain of yeast is not particularly limited, and preferred examples include yeasts of the genus Saccharomyces such as Saccharomyces cerevisiae.
  • the content rate of yeast can be suitably selected according to the purpose.
  • one or more of the lactic acid bacteria are cultured in a medium, or one or more of the lactic acid bacteria and one or more of the yeast are mixed and cultured in a medium.
  • a medium raw material medium containing the animal milk protein, or yeast extract, vitamins such as ascorbic acid, amino acids such as cysteine, salts such as sodium chloride, glucose, sucrose, raffinose, stachyose as secondary components.
  • a stabilizer such as gelatin, a stabilizer such as gelatin, and a flavor are appropriately added can be used.
  • Fermentation can be performed at a fermentation temperature of 25 to 50 ° C., preferably 30 to 45 ° C., usually by standing or stirring culture so that the IPP and VPP can be obtained, and the fermentation time is 6 to 30 hours. It is preferably 10 to 24 hours. It can be performed by a method of stopping the culture when the number of bacteria reaches 10 7 cells / ml or more and pH 5.0 or less under conditions such as the initial pH of fermentation of 6.0 to 7.0. Moreover, the animal milk protein before fermentation may be subjected to high-temperature heat sterilization or the like.
  • a peptidase capable of cleaving the Pro Xaa sequence at the carboxy terminus of the Xaa Pro Xaa sequence or Xaa Pro Pro Xaa sequence (Xaa represents an arbitrary amino acid) in animal milk protein for example, a peptidase capable of cleaving the Pro Xaa sequence at the carboxy terminus of the Xaa Pro Xaa sequence or Xaa Pro Pro Xaa sequence (Xaa represents an arbitrary amino acid) in animal milk protein.
  • Preferred examples include enzymes.
  • the enzyme preferably contains a serine type proteinase having serine at the active center or a metal proteinase having metal at the active center.
  • metal proteinases examples include neutral protease I, neutral protease II, leucine aminopeptidase, and the like, and further including at least one of these can efficiently produce a desired hydrolyzate in a short time, This is preferable because it can be obtained by a one-step reaction.
  • the peptidase that can cleave the Pro Xaa sequence is preferably an enzyme having an isoelectric point in the acidic region.
  • the enzyme examples include an enzyme group derived from Aspergillus oryzae and other koji molds.
  • Such an enzyme group includes an enzyme group obtained by culturing cells in an appropriate medium and extracting the produced enzyme with water, and in particular, the isoelectric point of the enzyme group derived from Aspergillus oryzae has an acidic region.
  • the enzyme group which shows is preferably mentioned.
  • As the enzyme group derived from Aspergillus oryzae commercially available products can be used.
  • Sumiteam FP, LP or MP above, registered trademark, manufactured by Shin Nippon Chemical Co., Ltd.
  • Ummamizyme registered trademark, Amano Enzyme
  • Sternzyme B11024 PROHIDROXY AMPL (trade name, manufactured by Higuchi Shokai Co., Ltd.), Orientase ONS (registered trademark, manufactured by Hankyu Bioindustry Co., Ltd.), Denateam AP (registered trademark, Nagase Biochemical Co., Ltd.)
  • the use of Sumiteam FP registered trademark, manufactured by Shin Nippon Chemical Co., Ltd.
  • the optimum conditions are usually set. However, for example, the amount of enzyme used and the reaction time are determined according to the enzyme group used so that the hydrolyzate can be obtained. Changes can be made as appropriate.
  • the amount of the enzyme added is, for example, an enzyme / animal milk protein in an aqueous solution in which animal milk protein is dissolved in a mass ratio of 1/1000 or more, preferably 1/1000 to 1/10, particularly preferably 1/100 to 1. / 10, more preferably in an amount of 1/40 to 1/10.
  • the reaction conditions can be appropriately selected depending on the enzyme so that the desired hydrolyzate can be obtained, but the temperature is usually 25 to 60 ° C., preferably 45 to 55 ° C., and the pH is usually 3 to 10, preferably 5 To 9, particularly preferably 5 to 8.
  • the enzyme reaction time is usually 2 to 48 hours, preferably 7 to 15 hours.
  • the enzyme reaction can be terminated by inactivating the enzyme. Usually, the enzyme can be inactivated at 60 to 110 ° C. to stop the reaction.
  • the hydrolyzate obtained by the method (A), (B), and the method combining (A) and (B) can remove the precipitate by centrifugation or various filter treatments as necessary. it can.
  • the peptide which has a bitter taste and a odor can also be removed from the obtained hydrolyzate as needed. Removal of such bitter components and odor components can be performed using activated carbon, hydrophobic resin, or the like.
  • activated carbon can be added to the hydrolyzate obtained in an amount of 1 to 20% by mass based on the amount of animal milk protein used and reacted for 1 to 10 hours.
  • the used activated carbon can be removed by a known method such as centrifugation or membrane treatment.
  • the obtained hydrolyzate can be used as it is as the reducing agent of the present invention. Moreover, in order to improve the versatility of the hydrolyzate, it can be dried and made into a powder form after concentration. Such powders may contain various auxiliary additives in order to improve nutritional balance, flavor, and the like. For example, various carbohydrates, lipids, vitamins, minerals, sweeteners, fragrances, pigments, texture improving agents and the like can be mentioned.
  • the dosage of the reducing agent of the present invention is preferably about 1 mg to 30 g, particularly about 20 mg to 20 g in terms of solid matter, and preferably divided into several times a day for the subject human subject per day. May be taken.
  • the administration period is usually 1 day or longer, preferably 20 days or longer, and it is desirable to take ingestion continuously or continuously.
  • the administration method is oral intake.
  • Examples of the form of the reducing agent of the present invention include tablets, pills, hard capsules, soft capsules, microcapsules, powders, granules, liquids and the like.
  • the formulation is carried out, for example, as necessary, as a pharmaceutically acceptable carrier, adjuvant, excipient, excipient, preservative, stabilizer, binder, pH adjuster, buffer, thickener. , Gelling agents, preservatives, antioxidants, etc., can be manufactured in unit dosage forms required for generally accepted formulation practice.
  • the effect of the present invention is expected to be enhanced by using in combination with other drugs known to exhibit a normalizing action of Non-dipper such as olmesartan and altinolol arotinolol.
  • the mitigation agent of the present invention includes components used in foods and drinks as necessary, such as sugars, proteins, lipids, stabilizers, vitamins, minerals, flavors, or mixtures thereof. Can also be added.
  • Example 1 Preparation of CM4 fermented milk>
  • Commercial skim milk powder is dissolved in distilled water to a solid content of 9% (w / w), sterilized by heating at 105 ° C. for 10 minutes in an autoclave, cooled to room temperature, CM4 strain starter fermentation solution (bacteria Several 5 ⁇ 10 8 pieces / ml) was inoculated with 3% (v / w) and fermented at 37 ° C. for 24 hours in a stationary state to obtain CM4 fermented milk.
  • CM4 fermented milk 1 ml of CM4 fermented milk was directly centrifuged at 15000 rpm for 10 minutes, and the supernatant (whey) was recovered. 0.3 ml of this whey was adsorbed on a Sep-Pak Cartridge (manufactured by Waters) and washed with distilled water. It was eluted with 5 ml of methanol and dried under reduced pressure under centrifugal treatment. The dried product was dissolved in 0.3 ml of an aqueous solution of 0.05% trifluoroacetic acid and subjected to HPLC analysis under the following conditions.
  • CM4 fermented milk To the obtained CM4 fermented milk, stabilizers, sweeteners, flavors, and water were added, homogenized, filled into glass bottles 160 ml at a time, sterilized at 85 ° C, and used as a fermented milk product for subjects.
  • Table 1 shows the component analysis results of the fermented milk products for subjects. The amount of VPP in the subject day's fermented milk product for subjects was 2.53 mg and the amount of IPP was 1.52 mg.
  • ⁇ Selection of normal blood pressure Dipper and non-dipper subjects For 12 subjects aged 55 to 71 years who are not currently taking antihypertensive drugs and have no experience of severe hypertension, allergic asthma, severe liver or kidney disease, stroke, or myocardial infarction, The following blood pressure measurements were performed. Each subject was asked to wear a portable 24-hour automatic sphygmomanometer (model ES-H531, manufactured by Terumo Corporation) on the upper arm that was not the toe arm, and SBP, DBP and heart rate were measured every 30 minutes for 24 hours. As a result, 6 subjects who had an average SBP for 24 hours of less than 130 mmHg, an average DBP for 24 hours of 80 mmHg or less, and no abnormal heart rate were selected.
  • the average SBP reduction rate at 0:00 to 5:00 relative to the average SBP at 8:00 to 21:00 was calculated, and the reduction rate was 10% or more.
  • Subjects were classified as Dipper type, and less than 10% of subjects were classified as Non-dipper type.
  • the DBP type subject's SBP data is shown in Table 2
  • the DBP data is shown in Table 3
  • the non-dipper type subject's SBP data is shown in Table 4
  • the DBP data is shown in Table 5. Note that no change was observed in the heart rate of the subject during the measurement.
  • the fermented dairy product for test subject containing the hydrolyzate of animal milk protein according to the present invention is a healthy person having normal values of SBP and DBP defined in the present invention, and a specific non-dipper blood pressure daily It was found that systolic blood pressure from night to early morning can be effectively reduced for humans with fluctuations, and the risk of developing diseases due to blood pressure diurnal fluctuations that are likely to develop in the morning can be reduced. Note that no change was observed in the heart rate of the subject during the measurement.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présence invention concerne un agent qui réduit le risque d'installation d'une maladie résultant de fluctuations de la pression sanguine au cours de la journée du type ne diminuant pas la nuit et qui peut réduire l'installation d'une maladie résultant d'un risque de fluctuation de la pression sanguine au cours de la journée et encline à survenir vers le matin lorsque la pression sanguine systolique du petit matin diminue significativement de celle de la nuit chez des êtres humains présentant un profil particulier de fluctuation de la pression sanguine au cours de la journée du type ne diminuant pas la nuit, en particulier des individus en bonne santé affichant des valeurs normales de PAS et de PAD. L'agent est caractérisé en ce qu'il contient : un hydrolysat contenant du VPP et de l'IPP et qu'il est obtenu par hydrolyse des protéines de lait animal ; ou son concentré.
PCT/JP2011/071025 2010-11-09 2011-09-14 Agent permettant de réduire le risque d'installation d'une maladie résultant d'une fluctuation de la pression sanguine au cours de la journée du type ne diminuant pas la nuit Ceased WO2012063553A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2010251010A JP5797891B2 (ja) 2010-11-09 2010-11-09 Ｎｏｎ−ｄｉｐｐｅｒ型血圧日内変動による疾病発症リスク軽減剤
JP2010-251010 2010-11-09

Publications (1)

Publication Number Publication Date
WO2012063553A1 true WO2012063553A1 (fr) 2012-05-18

Family

ID=46050709

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2011/071025 Ceased WO2012063553A1 (fr) 2010-11-09 2011-09-14 Agent permettant de réduire le risque d'installation d'une maladie résultant d'une fluctuation de la pression sanguine au cours de la journée du type ne diminuant pas la nuit

Country Status (3)

Country Link
JP (1) JP5797891B2 (fr)
TW (1) TW201304800A (fr)
WO (1) WO2012063553A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102948476A (zh) * 2012-11-19 2013-03-06 陕西科技大学 一种基于瑞士乳杆菌发酵的含ace抑制肽的羊乳饮料的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1198978A (ja) * 1997-09-26 1999-04-13 The Calpis Co Ltd トリペプチド高生産性ラクトバチルス・ヘルベチカス乳酸菌

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1198978A (ja) * 1997-09-26 1999-04-13 The Calpis Co Ltd トリペプチド高生産性ラクトバチルス・ヘルベチカス乳酸菌

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
AKIO FUJIMURA: "Series Jikan Yakubutsu Chiryo no Jissen (3) Junkanki Shikkan no Jikan Yakubutsu Chiryo", JOURNAL OF JAPANESE SOCIETY OF HOSPITAL PHARMACISTS, vol. 37, no. 1, 2001, pages 25 - 27 *
HIROSHI IJIRI ET AL.: "Effect of Imidapril hydrochloride on blood pressure daily variations and autonomic nerve activities in essential hypertension. Evaluation by portable automatic blood pressure heart rate recorders", JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, vol. 29, no. 1/2, 1998, pages 301 - 302 *
ISAO KONO ET AL.: "Chrono-therapy of imidapril for essential hypertension", YAMANASHI IGAKU, vol. 25, 1997, pages 103 - 108 *
MIZUNO S ET AL.: "Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension", BR J NUTR., vol. 94, no. 1, 2005, pages 84 - 91 *
NAOYUKI YAMAMOTO: "Nyusankin no Ketsuatsu Koka Peptide", JAPANESE JOURNAL OF LACTIC ACID BACTERIA., vol. 18, no. 1, 2007, pages 22 - 30 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102948476A (zh) * 2012-11-19 2013-03-06 陕西科技大学 一种基于瑞士乳杆菌发酵的含ace抑制肽的羊乳饮料的制备方法

Also Published As

Publication number Publication date
TW201304800A (zh) 2013-02-01
JP5797891B2 (ja) 2015-10-21
JP2012102037A (ja) 2012-05-31

Similar Documents

Publication Publication Date Title
JP2011504363A (ja) 改良された生理活性ペプチドの生成
CN102488716B (zh) 丙酸杆菌发酵物在制造皮肤粗糙预防、改善剂中的应用
HUP0004617A2 (hu) Stresszellenes szerek és funkcionális élelmiszerek
CN101646444B (zh) 功能性胃肠病预防和/或治疗剂
JP4891069B2 (ja) 内因性メラトニン分泌リズムの位相調整又は振幅増強剤、及び概日リズム改善剤
US9533015B2 (en) Lactococcus lactis strains
US20150307549A1 (en) Agent for preventing arteriosclerosis, agent for suppressing vascular intimal thickening and agent for improving vascular endothelial function
JP5797891B2 (ja) Ｎｏｎ−ｄｉｐｐｅｒ型血圧日内変動による疾病発症リスク軽減剤
US7763281B2 (en) Antihypertensive peptide and use thereof
JP5292632B2 (ja) 心不全予防剤
US8883731B2 (en) Agent for reducing risk in onset of disease ascribable to non-dipper circadian rhythm of blood pressure
JP7800902B2 (ja) コラーゲンペプチド吸収促進組成物とその製造方法
US20230180778A1 (en) Milk fermentation process
TWI412372B (zh) 心衰竭預防劑
JP4947636B2 (ja) 肝障害予防又は抑制剤
JP2005224233A (ja) モズクの納豆菌醗酵物およびその用途
TWI414305B (zh) 腎衰竭預防劑
HK1176010B (en) Blood uric acid value lowering agent
HK1176010A (en) Blood uric acid value lowering agent

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11840461

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11840461

Country of ref document: EP

Kind code of ref document: A1