TWI667344B - Lactobacillus reuteri strain GMNL-263 and composition thereof capable of improving hypertension - Google Patents

Abstract

The present invention discloses a Lactobacillus composition comprising a Lactobacillus reuteri (Lactobacillus.reuteri) GMNL-263, wherein the Lactobacillus reuteri (Lactobacillus.reuteri) GMNL-263-based heat killed off bacteria through suppression The inflammatory cytokine IL-1β promotes the growth of Bifidobacterium and has the effect of lowering blood pressure, and the lactobacillus composition is a pharmaceutical composition, a nutritional supplement, a health food or a combination thereof.

Description

Lactobacillus reuteri strain GMNL-263 and composition thereof capable of improving hypertension

The present invention relates to a composition for lactobacilli for use in improving hypertension.

Blood pressure is the compression and pulsation of the heart, which in turn causes the blood to exert pressure on the vessel wall. By maintaining blood pressure, it promotes blood circulation throughout the body, and then carries out nutrient transmission and waste metabolism; there are two kinds of blood pressure, systolic blood pressure and diastolic blood pressure, which are when systole or diastole is involved in heart beat. Measured values; normal blood pressure range is systolic blood pressure 90-139 mmHg (highest reading) and diastolic blood pressure 60-89 mmHg (lowest reading).

Hypertension is a chronic disease with elevated arterial blood pressure. It is also the most common chronic disease in China. When the blood pressure rises, the burden of the heart pushing the blood in the blood vessels is increased, and the blood pressure continues to be equal to or higher than 140/90 mmHg. When mmHg) is high blood pressure, it is easy to be neglected because it rarely shows symptoms. It is usually found through screening or seeking other health problems. Some patients have headache, dizziness, dizziness, tinnitus, and even if they are serious or even dizzy. Injury or internal organ damage, in addition to its symptoms are often easily overlooked, often accompanied by serious complications; with age, the risk of hypertension also increases, and hypertension is the risk of cardiovascular disease The important factor of the increase in multiples is one of the main causes of cardiovascular deaths announced by the World Health Organization. Because it is a kind of chronic disease, patients have to take long-term medication control, which is a heavy expense for time or money.

Hypertension is classified as primary or secondary, and primary origin accounts for 90-95% of the cause, ie no There is a clear cause; the other is secondary, which is caused by other diseases, accounting for about 5-10%, such as diabetes, kidney disease, endocrine disease, chest and abdomen obesity, thyroid disease and acromegaly or physiological Abnormal reactions, such as the pro-inflammatory cytokine production (Krishnan et al., 2014), and the reduction of gastrointestinal probiotics (Li et al., 2017), are the causes of or exacerbate high blood pressure.

Among them, long-term type 2 diabetes mellitus (T2DM) is a typical example of the linkage between disease and hypertension. Because of the symptoms of renal artery and systemic arteriosclerosis, diabetic patients often cause peripheral vascular resistance. Systolic blood pressure rises, causing blood pressure to rise. Therefore, patients with type 2 diabetes often develop with hypertension, and hypertension can accelerate vascular disease, which can cause complications of brain, eye, heart, kidney and other organs, and significantly improve myocardial Infarction and stroke risk.

At present, the use of drugs to control high blood pressure is still the main treatment. However, although blood pressure can be stably controlled, but because patients have to take drugs for a long time, not only time and money are heavy burdens, but also risk of taking carelessly. For example, some drugs may be harmful to pregnant women or the fetus. For former diabetic patients, high blood pressure drugs may affect blood sugar, cause deterioration of diabetes or misdiagnosis of the disease; in addition, with the mechanism of the drug itself Different, such as the regulation of cell receptors, inhibition of blood pulsation or reduction of nerve conduction, etc., with a certain degree of side effects. Therefore, looking for other effective blood pressure-lowering pathways without side effects is necessary to solve and prevent today's high blood pressure problems. There are many studies on how to control and prevent high blood pressure through healthy foods.

The body's blood pressure regulation system is mainly through the Renin-Angiotensin System (RAS) to achieve blood pressure, body fluids and electrolyte balance, and in this system, angiotensin I-transferase (Angiotensin I- Converting Enzyme, ACE) It is an important enzyme in blood pressure regulation to raise blood pressure.

In the past, it was found that probiotic fermented milk has the effect of regulating blood pressure. Probiotics can break down casein through lactose hydrolase, and produce unequal amount of angiotensin I-converting enzyme inhibitor (ACE inhibitory peptide). Peptide) (Yamamoto, 1999) in turn lowers blood pressure; studies indicate that Lactobacillus helveticus ( L.helveticus ), Lactobacillus caseis ( L.caseis ), Lactobacillus rhamnosus ( L.rhamnosus ), Lactobacillus acidophilus ( L.acidophilus ), Lactobacillus fermentum ( Among the probiotics such as L. fermentum ), Lactobacillus bulgaricus ( L. bulgaricus ), Lactobacillus reuteri ( L. reuteri ), etc., special live bacterial strains can be screened, and the strain and the ACE inhibitory peptide are added to the fermented milk. By using strains to produce more ACE inhibitory peptides in fermented milk, it has the effect of lowering blood pressure in hypertensive patients (Beltran-Barrientos et al., 2016).

However, this part of the study is limited to some special live bacterial strains, and there are still some limitations and shortcomings in the implementation, there are quite high thresholds in the effective dosage and time of administration, and in the blood pressure reduction of probiotic products. A systematic retrospective study indicated that the body needs to take more than 1 x 10 ¹¹ cfu (colony forming unit) per day for more than eight weeks in order to have better blood pressure regulation (Khalesi et al., 2014).

In general, the current research is still limited to in vitro or animal experiments. Only human probiotics can improve blood pressure. There are not many clinical trial data. The relevant human data are used for hypertensive patients . Helveticus and Saccharomyces cerevisiae ( S. cerevisiae ) complex strain fermented milk (Hata et al., 1996), or L.helveticus CM4 fermented milk (Aihara et al., 2005) for normal people with high blood pressure, both have blood pressure lowering the effect; and for diabetes risk groups, containing probiotic and quality products at the same time contain the following strains of L. casei, L.acidophilus, L.rhamnosus, L.bulgaricus , Bifidobacterium Breve (B.Breve), B.longum, Streptococcus thermophiles ( S. thermophiles ), the results have a blood pressure regulation function (Mahboobi et al., 2014).

At present, the use of live bacteria fermented by fermented milk to produce ACE inhibiting peptides, and the user controls blood pressure by drinking, which is the main route. However, because the probiotics are not a pharmaceutical dosage form, but a healthy food type, and there is little human data support, it is often unclear about the effective dose and frequency of drinking; in addition, because the living bacteria preparation process is used or Improper preservation, causing pollution, overdue, etc., can easily lead to user health risks; and because the composition of fermented milk is often used as a metabolic substrate for lactic acid bacteria and for flavoring purposes, the ingredients often have additives such as sugar, which may have other concurrency It is not the most appropriate option for patients (such as diabetes) or those who want to control their caloric intake.

At present, the patent on probiotics for lowering blood pressure mainly focuses on the above-mentioned method of feeding live bacteria to fermented milk, and often has to combine the addition of several kinds of lactic acid bacteria, and the related patents are briefly described below.

Taiwan Patent Publication No. TW 201305331 and Chinese Patent Publication No. CN 102098923A disclose Swiss lactic acid bacteria which can be metabolized by animal milk to produce fermentation products VPP (Valine-Proline-Proline, lysine-proline-proline) and IPP (Isoleucine). -Proline-Proline, isoleucine-proline-proline, which inhibits ACE as a hypotensive agent; however, this invention is based on the inference that VPP and IPP have been reported to have the ability to inhibit ACE. The fermented milk can be used to lower blood pressure. However, there is no experimental data to support it, and the invention is still administered in the form of live bacteria. There is still potential in the efficacy and the risk of preservation of the live bacteria and the acceptable population of fermented milk. Sexual problems.

Taiwan Patent Publication No. TW 200603741 discloses a method for preparing ACE inhibitors are functional fermented milk containing, comprising the step in which a raw material milk for the milk fermentation inoculated with the appropriate amount of lactic acid was prepared, the lactic acid bacterium selected from Lactobacillus (Lactobacillus a group consisting of spp. ), Streptococcus spp. , and Bifidobacterium spp. , which produces fermented lactic acid to produce an ACE-inhibiting peptide, which has been shown to have hypotensive blood pressure in a mouse animal test. Efficacy; however, the invention is also administered by the live bacteria type of fermented milk, but still has the aforementioned unclear potential and the potential risk of living bacteria preservation, limited acceptable population of fermented milk components, and only experimental data of mice There is no human body data to prove the efficacy.

Although the related invention proposes probiotics as a method for lowering blood pressure, since the route belongs to healthy foods, there is little human clinical data support, and if the specified efficacy is required, the amount of bacteria needs to have considerable requirements, and often needs to be combined. ACE inhibitory peptides, by type of fermented milk, viable cell administration; in addition, the exception of L. helveticus, currently no single one active strain can be administered to human clinical study of the regulation of blood pressure-related, and on the L The study of .helveticus is also a fermented milk that requires a live bacterial type combined with the mechanism of ACE inhibition of peptides to achieve blood pressure lowering, and fermented milk has the risk of preservation and contamination of live bacteria, and the added ingredients are unable to ingest excess sugar. Or those who need to control the heat, it is still not a viable solution.

In view of this, the inventor of this case has a deep understanding of the shortcomings and defects of the previous case, but he has made improvements and innovations, and after years of painstaking research, he finally succeeded in completing the use of heat-killing bacteria to kill L. reuteri ( L. reuteri) GMNL-263, the invention can reduce blood pressure.

references

1. Krishnan, S. M., Sobey, C. G., Latz, E., Mansell, A., and Drummond, G. R. (2014) Br J Pharmacol 171, 5589-5602

2. Li, J., Zhao, F., Wang, Y., Chen, J., Tao, J., Tian, G., Wu, S., Liu, W., Cui, Q., Geng, B ., Zhang, W., Weldon, R., Auguste, K., Yang, L., Liu, X., Chen, L., Yang, X., Zhu, B., and Cai, J. (2017) Microbiome 5, 14

3. Yamamoto, N., and Takano, T. (1999) Nahrung 43, 159-164

4. Beltran-Barrientos, L. M., Hernandez-Mendoza, A., Torres-Llanez, M. J., Gonzalez-Cordova, A. F., and Vallejo-Cordoba, B. (2016) J Dairy Sci 99, 4099-4110

5. Khalesi, S., Sun, J., Buys, N., and Jayasinghe, R. (2014) Hypertension 64, 897-903

6. Hata, Y., Yamamoto, M., Ohni, M., Nakajima, K., Nakamura, Y., and Takano, T. (1996) Am J Clin Nutr 64, 767-771

7. Aihara, K, Kajimoto, O., Hirata, H., Takahashi, R., and Nakamura, Y. (2005) J Am Coll Nutr 24, 257-265

8. Mahboobi, S., Iraj, B., Maghsoudi, Z., Feizi, A., Ghiasvand, R., Askari, G., and Maayeshi, N. (2014) Int J Prev Med 5, 1239-1246

The present invention is based in the use of probiotic Lactobacillus reuteri (L.reuteri) GMNL-263 composition, to prevent high blood pressure or lowering blood pressure.

To achieve the foregoing object of the invention, the invention is a method for improving hypertension Lactobacillus composition comprising a Lactobacillus reuteri (Lactobacillus.reuteri, L.reuteri) GMNL-263 , wherein the line L. reuteri It is dead.

To achieve the above purpose of the invention, the aforementioned Lactobacillus reuteri (L.reuteri) GMNL-263, registered in Taiwan Food Industry Institute, numbered BCRC 910452, China Type Culture Collection (CCTCC), register number CCTCC M 209263 .

To achieve the foregoing object of the invention, wherein the Lactobacillus reuteri (L.reuteri) GMNL-263 can be used to control diabetes or for an intake of sugar groups.

To achieve the aforementioned object, the lactobacillus composition is a pharmaceutical composition, a nutritional supplement, a health food or a combination thereof.

To achieve the aforementioned object, the lactobacillus composition is administered in an oral dosage form.

For the purpose of the foregoing invention, the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier.

For the purpose of the foregoing invention, the lactobacillus composition may further comprise an edible material comprising water, fluid dairy, milk, concentrated milk, yogurt, yogurt, frozen yogurt, lactobacillus fermented beverage , milk powder, ice cream, cheese, cheese, soy milk, fermented soy milk, vegetable juice, juice, sports drinks, desserts, jellies, sweets, baby food, health foods, animal feed, Chinese herbal medicines or dietary supplements.

Another object of the present invention is to provide a system for the preparation of lactobacillus compositions to improve the use of the new composition of high blood pressure, wherein the composition comprises a Lactobacillus Lactobacillus reuteri (L.reuteri) GMNL-263, wherein the Lo Lactobacillus johnsonii is a dead bacterium.

To achieve the aforementioned object, the improvement of hypertension lowers blood pressure by inhibiting an inflammatory cytokine and increasing the growth of a probiotic group.

For the purpose of the foregoing invention, the proinflammatory cytokine is IL-1β.

For the purpose of the foregoing invention, the probiotic group refers to Bifidobacterium.

To achieve the aforementioned object of the invention, wherein the use specifically refers to improving hypertension in the diabetic population.

For the purpose of the foregoing invention, wherein the diabetes refers to type 2 diabetes.

According to the human clinical trial, the GMNL-263 which exists in the heat killing type in the composition has the effect of lowering blood pressure after nine months of observation, and the other strain of the same kind of GMNL-89 is Does not have this effect.

Another embodiment of the present invention also confirmed that the GMNL-263 system has a blood pressure lowering effect by lowering the human proinflammatory cytokine IL-1β by comparing the subject samples during the test.

Still another embodiment of the present invention also proves that taking GMNL-263 does improve the performance of Bifidobacterium in the probiotic group, and the Bifidobacterium performance increase has a statistically significant negative correlation with the net change in blood pressure, indicating that taking The performance of Bifidobacterium caused by GMNL-263 is enhanced, which promotes the effect of lowering blood pressure.

The present invention utilizes Lactobacillus reuteri (L.reuteri) GMNL-263, through heat killed off bacteria types, the effectiveness of the invention is to achieve the reduction of blood pressure; and further found that the mechanism by inhibiting proinflammatory cytokines, and enhancing The performance of Bifidobacterium in probiotics is different from the previous mode of inhibiting ACE; the present invention is further compared in parallel to prove that even if it is the same as L. reuteri, different colonies ( L. reuteri GMNL-89) It is impossible to express the effect of lowering blood pressure.

The present invention is a Lactobacillus composition, which belongs to a probiotic, and therefore is safe to use without drug side effects, and can be applied for prevention and treatment of hypertension; and the first disclosure is administered by dead bacteria, and can be lowered without fermenting milk. Blood pressure; the present invention further confirms that the efficacy of the GMNL-263 to lower blood pressure is not ubiquitous in the same species of L. reuteri, and further clinical testing is needed to confirm; and for the first time, inhibition of IL-1β and improvement of Bifidobacterium expression are proposed. It can be used as a probiotic to lower blood pressure.

Figure 1A is a human clinical trial group; Figure 1B is a human clinical trial procedure; Figure 2 is a correlation analysis between Mean arterial pressure (MAP) and probiotic Bifidobacterium.

The present invention is exemplified by the following examples, but the present invention is not limited by the following examples. The material used in the present invention, in addition to those specifically stated, are all readily available commercial materials, the use of the present invention is Lactobacillus reuteri (Lactobacilus reuteri, L.reuteri) GMNL- 263 [ hereinafter referred Generation GMNL-263] It is deposited at the Taiwan Food Industry Research Institute under the number BCRC 910452, China National Type Culture Collection (CCTCC), and the registration number is CCTCC M 209263.

Example 1. Heat killing GMNL-263 has the effect of lowering blood pressure

This example is a human clinical trial. In view of the fact that patients with type 2 diabetes tend to have high blood pressure, the patients were diagnosed with type 2 diabetes for more than 6 months, and the remaining conditions were: 7% <HbA1c (glycated hemoglobin) ,glycated hemoglobin)≦10%; age: 25~70 years old; BMI>18.5; exclusion conditions: pregnancy/pregnancy; major diseases within 3 years, such as cancer (except for benign tumors and stable control), renal failure/dialysis , heart disease, stroke, autoimmune disease, blood glucose supplements other than hypoglycemic drugs before and during the test, fixed probiotics, fixed antibiotics, liver and kidney dysfunction, gastrointestinal tract is not healthy, can not be taken orally By.

This example was submitted to the Changhua Christian Hospital in Taiwan on the clinical trial publication website (Clinicaltrial.gov) under the accession number NCT02274272. The Institutional Review Board (IRB) was numbered No. 140703. Figure 1A and Figure 1B illustrate the experimental design method and flow. For the parallel study, there is a control group, using a double-blind, random assignment method, 74 people are enrolled, randomly assigned to perform in three groups, deducting the leave tester, and finally analyzing the data. A total of 68 patients were placed in the placebo group (placebo, N=22), and the L. reuteri GMNL-89 live bacteria group (hereinafter referred to as GMNL-89) (GMNL-89, N=22 people). And taking the L. reuteri GMNL-263 heat sterilization group (GMNL-263, N=24 people) as two groups of probiotics test group; in addition, deducting one subject lost stool sample, therefore, fecal bacteria phase analysis The data was 67 people. Under the condition of using the current prescription drugs, the basic biochemical values, blood glucose and other metabolic indicators, intestinal bacteria and pro-inflammatory cytokines were discussed. Before taking the probiotics for six months and stopping taking them three times. Months, a total of nine months of change.

GMNL-89 live bacteria powder and GMNL-263 heat sterilization fungus powder are prepared by fermentation of Jingyue Biotechnology Co., Ltd., and the dose of GMNL-89 is 4×10 ⁹ ctu (colony forming unit)/day, GMNL-263 The dose was 2 x 10 ¹⁰ cells/day and continued for 6 months.

In terms of statistical analysis, the basic data were compared using Chi-quare test or two sample t-test; while the medication record and hypertension comparison were performed using Fisher exact test, and the other part was using two sample t-test.

First, the patient's basic data were analyzed. Table 1 compares the basic data of the three groups at the beginning of the trial. There is no significant difference between the three groups. Table 2 shows that the proportion of hypertension in the three groups is not statistically significant. The difference indicates that the background conditions of the three groups of subjects are close, and in terms of blood pressure, although these subjects have blood pressure controlled by drugs, there are no statistical differences between the three groups of drugs used in the study, so there is no The experimental error caused by the drug is possible, but the systolic blood pressure (SBP) is still relatively high, indicating poor blood pressure control.

The results of the experiment showed that after six months, the net change in glycated hemoglobin (HbA1c) in diabetic patients taking the GMNL-89 live bacteria group (representing the value of the first month after the sixth month, net change value: 6M-0M There was a significant decrease (-0.39±0.80, P<0.05); while the GMNL-263 heat sterilization group did not differ much from the placebo group (0.24±0.93), indicating that taking the GMNL-263 heat sterilization group would not Affect the blood sugar level of diabetic patients.

In terms of blood pressure (Table 3 ), the net change in systolic blood pressure (SBP) and mean blood pressure was significantly decreased in the GMNL-263 heat-killing group, and there was a statistically significant difference (P<0.05). ), indicating that GMNL-263 has the effect of lowering blood pressure; however, GMNL-89, which is also Lactobacillus reuteri, has no significant change in various blood pressure measurement values, indicating that it does not have the effect of regulating blood pressure. This comparison also shows that the blood pressure lowering effect is required for specific strains in the Lactobacillus reuteri strain, is not ubiquitous and easy to infer, and must be confirmed by experiments.

Example 2. Heat-killing GMNL-263 has the effect of lowering blood pressure by lowering the pro-inflammatory cytokine IL-1β.

In order to test the mechanism by which GMNL-263 achieves blood pressure lowering, the cytokine content change analysis is further carried out. First, blood samples from three groups of subjects at the beginning (0M) and six months (6M) were collected, and various cytokine contents were analyzed using an ELISA kit, including human IL-6 (Cat#900-K16). , PeproTech, USA), human IL-10 (Cat#900-K21, PeproTech, USA), human TNF-α (Cat# 50-114-2609, eBioscience, USA), human IL-1β (Cat# 437005, Biolegend , USA), the data processing is six months (6M) minus the net change value of the start (0M), and further statistical analysis with two sample t-test.

The results showed that after taking GMNL-263 for six months, the IL-1β in the blood of the patients showed a statistically significant decrease compared with the placebo group. In contrast, other cytokines did not differ much (Table 4 ). GMNL-263 regulates the systemic chronic inflammatory response by lowering IL-1β, thereby achieving the goal of lowering blood pressure.

Example 3, heat killing GMNL-263 has the effect of lowering blood pressure by improving the performance of Bifidobacterium in the intestine

To clarify whether the blood pressure lowering effect of GMNL-263 is related to the regulation of intestinal probiotics, collect the fecal samples from the beginning (0M) and six months (6M) of the subjects to quantify the polymerase chain reaction ( Quantitative polymerase chain reaction (Q-PCR) analyzes the DNA in the fecal bacteria phase and calculates the change in the growth and decline of the bacteria phase after taking the probiotic for six months. The calculation method is: (take six months of fecal DNA using Q-PCR) CT (Threshold cycle) value - CT value of total bacteria) = △ Ct, △ Ct - (CT value obtained by Q-PCR of fecal DNA of the untreated person - CT value of total bacteria) = △ △ Ct; It is 2 ^{- △ △ Ct} , which is the change of the growth and decline of the bacterial phase after taking the probiotic for six months.

The Q-PCR analysis of fecal bacteria phase can be divided into two parts: DNA extraction and Q-PCR analysis. First, the method of DNA extraction from stool samples is based on the DNA kit (QIAamp DNA Stool Mini Kit, QIAGEN, Lot.51504). After removing the RNA later protectant from the patient's stool, add Buffer ASL, then heat it on a 70 °C hot plate for 5 minutes, then add 0.1 mm sterilized microbeads (Model: BioSpec Products 0.1MM ZIRCONIA/SILICA BEADS, cat .No.11079101z) Strongly shake for at least 15 seconds until the feces are mixed and pulverized; centrifuge at 13,000 rpm for 1 minute, take the supernatant, and then extract the DNA, and adjust the extracted DNA to 1 ng/μl for use.

Then, fecal Q-PCR analysis was performed, and the extracted DNA was used as a template for Q-PCR. Each reaction reagent was added with 2 μl of 2× Rotor-Gene SYBR Green PCR Master Mix (QIAGEN, Cat. 204076). After fecal DNA, add 3 μl of the test phase primer (0.66 μM Forward(F)+Reverse primers(R)) to make a total volume of 10 μl, and perform an instant Q with a PCR machine (model QIAGEN: Rotor-Gene Q 2Plex). - PCR.

The bacterial phase change data was statistically analyzed by Two sample t-test; and the correlation analysis between the bacterial phase change and the blood pressure change was performed by the statistical software PASW Statistics 18 Software (SPSS Inc) for Spearman's rho correlation.

The results showed that Bifidobacterium expression in the probiotic flora of the subjects was observed to increase after six months of heat killing of GMNL-263, compared with the placebo group, according to statistically significant differences (Table 5 ); In order to clarify the relationship between bacterial phase and blood pressure changes, and further use correlation statistical analysis, it was found that the increase in Bifidobacterium content was negatively correlated with the mean change in mean blood pressure (R=-0.268, P=0.028, Figure 2 ), indicating When the amount of Bifidobacterium is high, it will promote blood pressure lowering. Therefore, it was proved that the heat killing of GMNL-263 can achieve the effect of lowering blood pressure by increasing the Bifidobacterium in the probiotics in the feces.

Table 5. Microbial changes after three months of experiment in three groups of subjects

The invention proves that taking heat-killing L. reuteri GMNL-263 can help diabetic patients with hypertension symptoms reduce systolic blood pressure and average blood pressure after six months without affecting blood sugar level, and need to control sugar or caloric intake. The group or the diabetic patient is very helpful; the strain is heat-killed and can be made into capsules or powder packs, which has the advantages of high stability and simplicity; in addition, because the lactobacillus belong to probiotics, it is healthy. Food, therefore, there is no safety concern, and can be used by ordinary people to prevent or control high blood pressure. The use of ethnic groups is unlimited and can be applied in a wide range. The present invention further confirms the heat killing of Roy's milk by correlation statistical analysis. Bacillus GMNL-263 simultaneously achieves a blood pressure lowering effect by lowering the proinflammatory cytokine IL-1β and regulating the intestinal flora of the patient to increase the bifidobacteria in the probiotic bacteria; and by the same species control The group GMNL-89 proved that not all Lactobacillus reuteri can be used for lowering blood pressure, requiring specific strains, and can be confirmed by clinical trials. The above-mentioned invention of Lactobacillus reuteri GMNL-263 for lowering blood pressure is the first discovery of probiotics for blood pressure lowering applications, and breaks the form of the previous case and the use group restrictions.

This case is not only innovative in terms of technical thinking, but also has many functions that are not in the traditional methods of the past. It has fully complied with the statutory invention patent requirements of novelty and progressiveness, and applied for it according to law. You are requested to approve the invention patent application. In order to invent, to the sense of virtue.

【Biomaterial Storage】

Domestic registration information [please note according to the registration authority, date, number order]

1. Depository institution - Food Industry Development Research Institute, storage date - November 6, 2009, registration number - BCRC 910452

Foreign deposit information [please note according to the country, organization, date, number order]

1. Host country - China, depository - China Type Culture Collection (CCTCC), deposit date - November 13, 2009, deposit number - CCTCC M 209263

Claims (11)

A milk Lactobacillus use for high blood pressure producing improved pharmaceutical composition, wherein the composition comprises a Lactobacillus Lactobacillus reuteri (L.reuteri) GMNL-263, wherein the dead line L. reuteri bacteria. The use according to claim 1, wherein the improvement of hypertension lowers blood pressure by inhibiting an inflammatory cytokine and increasing the growth of a probiotic group. The use according to claim 2, wherein the proinflammatory cytokine is IL-1β. The use according to claim 2, wherein the probiotic group is Bifidobacterium. The use of claim 1, wherein the use specifically refers to improving hypertension in a diabetic population. The use of claim 5, wherein the diabetes refers to type 2 diabetes. The application for the use according to item 1 patentable scope, wherein the Lactobacillus reuteri (L.reuteri) GMNL-263 registers the number BCRC 910452. The use according to claim 1, wherein the Lactobacillus pharmaceutical composition is administered in an oral dosage form. The use of claim 8, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier. Comprising Lactobacillus reuteri (L.reuteri) GMNL-263 is a health food for modulating blood pressure, wherein the dead line L. reuteri bacteria. The use of claim 10, wherein the health food product further comprises An edible material comprising water, fluid dairy, milk, concentrated milk, yogurt, yogurt, frozen yogurt, lactobacillus fermented beverage, milk powder, ice cream, cheese, cheese, soy milk, fermented soy milk, fruits and vegetables Juice, juice, sports drinks, desserts, jellies, sweets, baby food, health foods, animal feed, Chinese herbal medicines or dietary supplements.