[go: up one dir, main page]

CN119235014A - Use of a pitaya probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora - Google Patents

Use of a pitaya probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora Download PDF

Info

Publication number
CN119235014A
CN119235014A CN202411305154.1A CN202411305154A CN119235014A CN 119235014 A CN119235014 A CN 119235014A CN 202411305154 A CN202411305154 A CN 202411305154A CN 119235014 A CN119235014 A CN 119235014A
Authority
CN
China
Prior art keywords
composition
powder
probiotic
bifidobacterium
probiotics
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.)
Pending
Application number
CN202411305154.1A
Other languages
Chinese (zh)
Inventor
李思佳
孙雨薇
李靖
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.)
Nanjing Aurora Biotechnology Co ltd
Original Assignee
Nanjing Aurora Biotechnology 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 Nanjing Aurora Biotechnology Co ltd filed Critical Nanjing Aurora Biotechnology Co ltd
Priority to CN202411305154.1A priority Critical patent/CN119235014A/en
Publication of CN119235014A publication Critical patent/CN119235014A/en
Pending legal-status Critical Current

Links

Landscapes

  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了一种益生菌组合物在快速促进排便、维持肠道菌群稳定中的用途,属于益生菌补充剂领域。本发明提供了一种特定组分和配方的组合物,该组合物在益生菌、水溶性膳食纤维、火龙果粉的作用下,能够在24小时内快速促进成人排便,迅速解决患者的便秘问题;同时安全性高,不含有泻药成分,避免刺激肠道;三种益生菌能够平衡肠道菌群,使患者能够保持长期规律排便。在粉剂的制备过程中添加竹子提取物粉,能够提高粉剂的流动性,使各组分混合更加均匀。The present invention discloses a use of a probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora, and belongs to the field of probiotic supplements. The present invention provides a composition of specific components and formulas, which, under the action of probiotics, water-soluble dietary fiber, and pitaya powder, can rapidly promote adult defecation within 24 hours and quickly solve the patient's constipation problem; at the same time, it has high safety, does not contain laxative ingredients, and avoids irritating the intestine; the three probiotics can balance the intestinal flora, so that the patient can maintain long-term regular defecation. Adding bamboo extract powder during the preparation of the powder can improve the fluidity of the powder and make the components mixed more evenly.

Description

Application of dragon fruit probiotic composition in rapid defecation promotion and intestinal flora stabilization maintenance
Technical Field
The invention relates to the field of probiotic supplements, in particular to application of a probiotic composition in rapid defecation promotion and intestinal flora stabilization maintenance.
Background
Constipation is a clinically common symptom caused by various pathological factors, and is mainly characterized by less defecation times, difficult defecation or too hard feces. The findings indicate that a significant proportion of people experience constipation and that their health hazards are often ignored as they rarely lead to hospitalization or death. However, the disease incidence is high, the etiology is complex, and a lot of pains and trouble are often brought to patients, so that the physical health and the quality of life of people are seriously affected. Modern medicine has demonstrated that chronic constipation can induce a variety of different diseases, such as rectal cancer, hypertension, cerebral apoplexy, stroke, etc. Therefore, when constipation symptoms occur, people need to pay attention to the constipation symptoms, and proper treatment is performed.
A large number of researches show that probiotics and dietary fibers can effectively improve constipation due to the safety of the probiotics and dietary fibers, and the probiotics and dietary fibers are favored by researchers.
Probiotics are active microorganisms beneficial to the human body, which can improve intestinal health through a variety of mechanisms, and have remarkable effects in relieving constipation in particular. The probiotics can help to restore and maintain the balance of flora in the intestinal tract, promote the propagation of beneficial bacteria by inhibiting the growth of harmful bacteria, improve the intestinal environment, stimulate the peristalsis of the intestinal tract, promote the movement and discharge of feces, increase the absorption of moisture in the intestinal tract, promote the secretion of intestinal mucus and enable the intestinal mucus to be discharged more easily, and enhance the immune function of the intestinal tract and reduce the inflammation of the intestinal tract. Intestinal inflammation and immune dysfunction are also factors that lead to constipation.
The dragon fruit powder is powder obtained by drying and grinding dragon fruits, and has rich nutritional ingredients including dietary fibers, vitamins, minerals and antioxidant substances. The dietary fiber can increase the volume and weight of the feces, promote intestinal peristalsis, and help relieve constipation, wherein the soluble fiber can absorb water to form a gelatinous substance, so that the feces become soft and are easy to discharge, and meanwhile, the fiber can serve as food of intestinal probiotics, promote the growth of the probiotics and improve the intestinal microecological environment, thereby helping to relieve constipation. In addition, the rich antioxidant substances such as vitamin C and anthocyanin are beneficial to reducing intestinal inflammation and promoting intestinal health. The dragon fruit seed is a small black seed in the dragon fruit, and is usually eaten together with the dragon fruit when eating. He is also rich in dietary fiber, and can promote intestinal peristalsis, help digestion, and prevent constipation. The dragon fruit seed liquid is rich in various minerals such as magnesium, calcium, iron and zinc. These minerals play an important role in both immune function and overall metabolism.
A great deal of researches show that the intestinal microecological environment of constipation patients is changed, and the intestinal microecological environment is mainly characterized in that the number of bifidobacteria beneficial to human bodies is obviously reduced, potential pathogenic bacteria and external pathogenic bacteria overgrow, and intestinal dysfunction symptoms such as constipation and the like are generated. At present, western medicine mostly adopts cathartic, prokinetic agent and other medicines to treat the disease, and the symptoms of patients can only be temporarily relieved when the medicines are taken, and the medicines have more side effects, can stimulate intestinal tracts, and are easy to form medicine dependence. Therefore, research and development of probiotic treatment methods is very necessary.
There is a need for a composition that can rapidly promote defecation, improve intestinal motility, balance intestinal flora, but at the same time has little side effects and does not cause disturbance of intestinal flora to meet the needs of people.
Disclosure of Invention
In one aspect, the invention provides a probiotic composition comprising probiotics, wherein the number of viable probiotic bacteria in each 1g of the composition is 25-600 hundred million.
In some embodiments, bamboo extract is also included.
In some embodiments, the bamboo extract is 9-225mg, preferably 12-75mg per 1g of composition.
In some embodiments, the bamboo extract is 15-25mg per 1g of composition.
In some embodiments, the bamboo extract is prepared by cleaning fresh bamboo leaves, slicing, pretreating, steaming and boiling treated bamboo, filtering to obtain filtrate, and distilling under reduced pressure to obtain bamboo extract.
In some embodiments, the probiotic bacteria include, but are not limited to, bifidobacterium lactis, lactobacillus rhamnosus, bacillus coagulans, lactobacillus plantarum, lactobacillus acidophilus, bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium infantis, lactobacillus casei, bifidum biphenicum, lactobacillus raman, bifidobacterium longum, bifidobacterium breve, bifidobacterium thermophilum.
In some embodiments, the probiotic is animal bifidobacterium subspecies, lactobacillus rhamnosus, lactobacillus plantarum.
In some embodiments, the live number of probiotics in each 1g of the composition is 100-400 hundred million, preferably 175-200 hundred million.
In some embodiments, water-soluble dietary fibers are also included in the composition, including, but not limited to, polydextrose, fructooligosaccharides, isomaltooligosaccharides, lactose oligosaccharides, soy oligosaccharides, agar powder, carboxymethyl cellulose, cereal dietary fibers, vegetable and fruit dietary fibers, nut and seed dietary fibers, and seaweed dietary fibers.
In some embodiments, the cereal dietary fiber includes, but is not limited to dietary fiber in foods such as whole grains, miscellaneous cereals, beans, and the like, specifically including sweet potatoes, purple potatoes, corn, brown rice, barley, buckwheat, oats, kidney beans, mung beans, small beans, broad beans, peas, cowpeas, lentils, black beans.
In some embodiments, vegetable and fruit dietary fibers include, but are not limited to, broccoli, carrot, apple, banana, cucumber, towel gourd, eggplant, tomato.
In some embodiments, the nut and seed dietary fibers include, but are not limited to, almonds, flaxseeds, chia seeds, walnuts, pistachios, almonds, pine nuts.
In some embodiments, the seaweed dietary fibers include, but are not limited to, undaria pinnatifida, laver, kelp.
In some embodiments, the probiotics have a live count to water soluble dietary fiber mass ratio of 25-600 hundred million 36-810mg, preferably 100-400 hundred million 48-270mg, and more preferably 175-200 hundred million 60-90mg.
In some embodiments, the water-soluble dietary fiber is 36-810mg, preferably 48-270mg, more preferably 60-90mg, per 1g of composition.
In some embodiments, sugar alcohols are also included in the composition, including but not limited to sorbitol, maltitol, mannitol, lactitol, erythritol, xylitol.
In some embodiments, the sugar alcohol is sorbitol.
In some embodiments, the probiotic bacteria have a viable count to sugar alcohol mass ratio of 25 to 600 hundred million, 0.36 to 8.1g, preferably 100 to 400 hundred million, 0.48 to 2.7g, and more preferably 175 to 200 hundred million, 0.6 to 0.9g.
In some embodiments, the sugar alcohol is present in an amount of 0.36 to 8.1g, preferably 0.48 to 2.7g, more preferably 0.6 to 0.9g per 1g of the composition.
In some embodiments, the probiotic bacteria further comprise dragon fruit powder, wherein the mass ratio of the viable bacteria number of the probiotic bacteria to the dragon fruit powder is 100-2400 hundred million, preferably 400-1600 hundred million, 0.5-10mg, and more preferably 700-800 hundred million, 0.5-10mg.
In some embodiments, the dragon fruit powder is 0.1-2.5mg by mass, specifically 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5 per 1g of composition.
In some embodiments, the present invention further comprises an acid milk powder.
In another aspect, the invention provides a product prepared from the above composition in the form of a tablet, capsule, powder, oral liquid, suspension, jelly, soft candy or pellet.
In some embodiments, powders are prepared from the above-described compositions.
In some embodiments, the powder is prepared by mixing powders of various materials in the composition uniformly and then filling to obtain the product.
In another aspect, the present invention provides the use of the above-described compositions and products for rapidly promoting bowel movement, maintaining balance of intestinal flora, and improving intestinal motility.
In some embodiments, the compositions provided herein are administered in 1-2 bags per day, as a drink or as a hot water at a temperature below 37 ℃.
The invention has the beneficial effects that:
1. The composition can promote adult defecation within 24 hours under the action of probiotics, water-soluble dietary fiber and dragon fruit powder, and can rapidly solve constipation problem of patients.
2. The composition has high safety, and contains no cathartic component, and can avoid intestinal tract irritation.
3. Three probiotics can balance intestinal flora, so that patients can keep long-term regular defecation.
4. The bamboo extract powder is added in the preparation process of the powder, so that the fluidity of the powder can be improved, and the components are more uniformly mixed.
Detailed Description
The invention will be further illustrated by the following examples, which are not intended to limit the scope of the invention, in order to facilitate the understanding of those skilled in the art.
Example 1
4G of a composition, wherein the probiotic powder contains animal bifidobacterium subspecies HN019, lactobacillus rhamnosus GG and lactobacillus plantarum PL15A, the viable count of the probiotic is 750 hundred million, the polydextrose is 300mg, the sorbitol is 3000mg, the appropriate amount of dragon fruit powder and the bamboo extract powder are 80mg.
Example 2
4G of composition, wherein the probiotic powder contains animal bifidobacterium subspecies HN019, lactobacillus rhamnosus GG and lactobacillus plantarum PL15A, the viable count of the probiotic is 700 hundred million, the polydextrose is 240mg, the sorbitol is 3600mg, a proper amount of dragon fruit powder and bamboo extract powder is 60mg.
Example 3
4G of composition, wherein the probiotic powder contains animal bifidobacterium subspecies HN019, lactobacillus rhamnosus GG and lactobacillus plantarum PL15A, the viable count of the probiotic is 800 hundred million, 360mg of polydextrose, 2400mg of sorbitol, a proper amount of dragon fruit powder and 100mg of bamboo extract powder.
Comparative example 1
A composition 4g comprises probiotic powder containing Bifidobacterium bifidum B11, lactobacillus rhamnosus GG, lactobacillus plantarum PL15A, viable count of probiotic is 750 hundred million, polydextrose 300mg, sorbitol 3000mg, appropriate amount of dragon fruit powder, and bamboo extract powder 80mg.
Comparative example 2
4G of composition, wherein the probiotic powder contains animal bifidobacterium subspecies HN019, lactobacillus rhamnosus GG and lactobacillus casei LC-12, the viable count of the probiotic is 750 hundred million, the polydextrose is 300mg, the sorbitol is 3000mg, the appropriate amount of dragon fruit powder and the bamboo extract powder is 80mg.
Comparative example 3
4G of a composition, wherein the probiotic powder comprises animal bifidobacterium subspecies HN019, lactobacillus casei LC-12, lactobacillus plantarum PL15A, the viable count of the probiotic is 750 hundred million, polydextrose 300mg, sorbitol 3000mg and bamboo extract powder 80mg.
Comparative example 4
4G of composition, wherein the probiotic powder contains animal bifidobacterium subspecies, lactobacillus rhamnosus and lactobacillus plantarum, the viable count of the probiotic is 750 hundred million, polydextrose is 300mg, lactitol is 3000mg, a proper amount of dragon fruit powder and bamboo extract powder is 80mg.
Comparative example 5
4G of composition, wherein the probiotic powder contains animal bifidobacterium subspecies, lactobacillus rhamnosus and lactobacillus plantarum, the viable count of the probiotic is 750 hundred million, 300mg of fructo-oligosaccharide, 3000mg of sorbitol, a proper amount of dragon fruit powder and 80mg of bamboo extract powder.
Comparative example 6
4G of composition, wherein the probiotic powder contains animal bifidobacterium subspecies HN019, lactobacillus rhamnosus GG and lactobacillus plantarum PL15A, the viable count of the probiotic is 750 hundred million, the polydextrose is 300mg, the sorbitol is 3000mg, and a proper amount of dragon fruit powder.
EXAMPLE 6 evaluation test of efficacy of promoting defecation
55 Mice were taken and each group was divided randomly into a blank control group, a model control group, examples 1-8 and a positive control group. Except for the blank control group, all the groups of mice are prevented from being fasted for 72 hours to form a dryness-accumulation water-loss constipation model.
Administration was performed in the following manner, a blank group was free diet; the model control group is water-forbidden and non-fasted, the positive control group is water-forbidden and non-fasted, the compound diphenoxylate is fed according to the administration dosage of 15 mg/(kg.d), and the examples 1-8 are subjected to gastric lavage according to the administration dosage of 250 mg/(kg.d) by preparing the compositions of the examples 1-8 and distilled water into a suspension with the concentration of 2 g/L.
After administration, the mice were placed in a mouse cage, white clean filter paper was laid down, and the total weight of the feces of the mice in the first defecation time (min) and 24 hours was recorded by observation, and the results are shown in Table 1.
First defecation time, which is the time from the end of gastric lavage to the first defecation.
TABLE 1
Example 7 Constipation improving Effect of the composition of the example
Purpose of trial eating, verify Constipation improving effect of example 1
Crowd-in subjects criteria for inclusion (as long as one of the criteria is met) are as follows:
① The defecation times are <2 times/week;
② A person with difficult defecation;
③ The hardness of the feces is high;
④ From the people who think that the defecation or constipation needs to be improved
The test design is that 17 persons take the example 1 for 3 days;
The administration mode is that 1 bag is taken on the first day by 1-2 persons meeting the inclusion standard, and 2 bags can be added according to the effect on the first day;
the patients who meet the inclusion standard 3 items take 2 bags directly on the first day;
Only meeting the inclusion standard ④, taking 1 bag on the first day, and increasing to 2 bags according to the first day effect;
The questionnaire content is 1. The main standard is ① defecation frequency, ② defecation condition, ③ defecation condition, ④ defecation condition and ⑤ defecation time;
2. the secondary standard is to record whether adverse reactions (nausea, vomiting, diarrhea, abdominal pain, abnormal feces, etc.) exist.
TABLE 2
EXAMPLE 8 determination of powder flowability
The angle of repose of the compositions prepared in examples 1-3 and comparative example 6 was determined according to the injection method. Example 1 had the best flowability, examples 2-3 were not very different between 30-40, while comparative example 6 had an angle of repose greater than 50%, greater than 45 degrees and had poor flowability.
TABLE 3 Table 3
Sample of Angle of repose/°
Example 1 32.24
Example 2 35.52
Example 3 35.91
Comparative example 6 55.68
It should be understood that the detailed description of the technical solution of the present invention, given by way of preferred embodiments, is illustrative and not restrictive. Modifications and substitutions for some technical features of the embodiments may be made by those skilled in the art based on the present disclosure, and the essence of the corresponding technical solutions does not deviate from the spirit and scope of the technical solutions of the embodiments.

Claims (19)

1. The dragon fruit powder probiotic composition is characterized by comprising probiotics, wherein the number of live probiotics in the composition is 25-600 hundred million/g.
2. The composition of claim 1, further comprising bamboo extract.
3. A composition according to claim 2, wherein the bamboo extract is present in the composition in an amount of 9-225mg/g, preferably 12-75mg/g.
4. A composition according to claim 3 wherein the bamboo extract is present in the composition at 15-25mg/g.
5. The composition of claim 2, wherein the preparation method comprises washing fresh bamboo leaves, slicing, pretreating, steaming and boiling treated bamboo, filtering to obtain filtrate, and distilling under reduced pressure to obtain bamboo extract.
6. The composition of claim 1, wherein the probiotic is one or a combination of several of bifidobacterium lactis, lactobacillus rhamnosus, bacillus coagulans, lactobacillus plantarum, lactobacillus acidophilus, bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium infantis, lactobacillus casei, bifidum, lactobacillus raman, bifidobacterium longum, bifidobacterium breve, bifidobacterium thermophilum.
7. The composition of claim 6, wherein the probiotic is animal bifidobacterium subspecies, lactobacillus rhamnosus, lactobacillus plantarum.
8. A composition according to claim 1, wherein the number of live probiotic bacteria in the composition is from 100 to 400 million/g, preferably from 175 to 200 million/g, in the composition.
9. The composition according to claim 1, wherein the composition further comprises water-soluble dietary fibers, preferably one or a combination of several of polydextrose, fructooligosaccharides, isomaltooligosaccharides, galactooligosaccharides, xylooligosaccharides, soy oligosaccharides, agar powder, carboxymethyl cellulose, cereal dietary fibers, vegetable and fruit dietary fibers, nut and seed dietary fibers, seaweed dietary fibers.
10. The composition according to claim 9, wherein the mass ratio of the viable count of the probiotics to the water-soluble dietary fiber is 25-600 hundred million, 36-810mg, preferably 100-400 hundred million, 48-270mg, further preferably 175-200 hundred million, 60-90mg.
11. The composition according to claim 1, wherein the composition further comprises a sugar alcohol, preferably one or a combination of sorbitol, maltitol, mannitol, lactitol, erythritol, xylitol.
12. The composition of claim 11, wherein the sugar alcohol is sorbitol.
13. The composition according to claim 11, wherein the mass ratio of live bacteria to sugar alcohol of the probiotics is 25-600 hundred million, 0.36-8.1g, preferably 100-400 hundred million, 0.48-2.7g, further preferably 175-200 hundred million, 0.6-0.9g.
14. The composition of claim 1, further comprising dragon fruit powder.
15. Composition according to claim 14, wherein the mass ratio of live bacteria to dragon fruit powder of the probiotics is 100-2400 million, preferably 400-1600 million, 0.5-10mg, further preferably 700-800 million, 0.5-10mg.
16. The composition of claim 1, further comprising an acid milk powder.
17. A product, characterized in that it is prepared from the composition according to any one of claims 1 to 16 in the form of a tablet, capsule, powder, oral liquid, suspension, jelly, soft candy or pellet.
18. The product of claim 17, wherein the composition of any one of claims 1-16 is formulated as a powder.
19. Use of a composition according to any one of claims 1-16 and a product according to any one of claims 17-18 for rapidly promoting bowel movement, maintaining intestinal flora balance, and improving intestinal motility.
CN202411305154.1A 2024-09-19 2024-09-19 Use of a pitaya probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora Pending CN119235014A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202411305154.1A CN119235014A (en) 2024-09-19 2024-09-19 Use of a pitaya probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202411305154.1A CN119235014A (en) 2024-09-19 2024-09-19 Use of a pitaya probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora

Publications (1)

Publication Number Publication Date
CN119235014A true CN119235014A (en) 2025-01-03

Family

ID=94015989

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202411305154.1A Pending CN119235014A (en) 2024-09-19 2024-09-19 Use of a pitaya probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora

Country Status (1)

Country Link
CN (1) CN119235014A (en)

Similar Documents

Publication Publication Date Title
JP6271571B2 (en) Composition for maintaining intestinal microbiota equilibrium, process for producing the composition, and use of the composition
CN111972670A (en) Composition for relaxing bowel, solid beverage and application
CN106954847A (en) Ferment probiotic composition with function of relaxing bowel, using and process preparation
CN111528479A (en) Probiotics and prebiotics composition for relieving atopic dermatitis function and application
CN111557404A (en) Digestion-aiding probiotic solid beverage and preparation method thereof
CN105596605A (en) Composition with bowel relaxing and sleep improving functions and preparation method thereof
CN116549494B (en) Beta-1, 3/alpha-1, 3-glucan compound composition with bowel relaxing function and preparation method and application thereof
US10369184B2 (en) Composition and use thereof in manufacture of product for improving intestinal function
CN112021564A (en) Composition for maintaining stomach and intestine and preparation method and application thereof
CN114831286A (en) Composition with constipation relieving function and preparation method thereof
CN114287633A (en) Probiotic composition containing cranberry and application of probiotic composition in resisting helicobacter pylori
CN112626001B (en) Probiotic composition for promoting growth of butyric acid bacteria and application thereof
CN111528486A (en) Composition containing lactoferrin
CN113750113B (en) Composition of probiotics and prebiotics and application thereof
CN109645501A (en) A kind of galactooligosaccharide composition and its application of defaecation and reduction flatulence
CN108887688A (en) A kind of multifarious dietary fiber and preparation method thereof
CN113575963A (en) Oligosaccharide probiotic composition and preparation method thereof
CN108938789A (en) A kind of more bacterium combination formulations of the adjusting intestinal microecology containing xylo-oligosaccharide
CN103689748A (en) Instant drink capable of regulating gastrointestinal function and preventing constipation
CN119235014A (en) Use of a pitaya probiotic composition in rapidly promoting defecation and maintaining the stability of intestinal flora
CN110538218A (en) Composition for treating mastitis
WO2014134830A1 (en) Edible composition, food product comprising same, and preparation method for the food product
WO2021111981A1 (en) Agent for prevention or remediation of dementia and composition containing same
CN110169984B (en) Application of Nostoc flagelliforme powder in regulating intestinal flora structure
CN116349815A (en) Production formula of viable bacteria type probiotic solid beverage capable of regulating intestinal flora

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination