CN115463160A - Probiotic supplement capable of being rapidly released in oral cavity and preparation method thereof - Google Patents

Probiotic supplement capable of being rapidly released in oral cavity and preparation method thereof Download PDF

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CN115463160A
CN115463160A CN202211099580.5A CN202211099580A CN115463160A CN 115463160 A CN115463160 A CN 115463160A CN 202211099580 A CN202211099580 A CN 202211099580A CN 115463160 A CN115463160 A CN 115463160A
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probiotic supplement
probiotic
supplement
unit dose
probiotics
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王彦峰
刘荣
王倜
李晓静
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Beijing Quantum Hi Tech Pharmacy Technology Co ltd
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Beijing Quantum Hi Tech Pharmacy Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants

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Abstract

The invention provides an intraorally rapidly-released probiotic supplement, which comprises 5-80mg of probiotics, 6-12mg of a supporting agent and 6-12mg of pullulan in unit dose, and comprises a suspending agent of less than 0.2mg in unit dose. The probiotic supplement released quickly in the oral cavity can load high-dose probiotics, is quickly disintegrated in the oral cavity, has good taste, is high in survival rate of the probiotics in the preparation, and is suitable for children, particularly infants to take.

Description

Probiotic supplement capable of being rapidly released in oral cavity and preparation method thereof
The application is a divisional application of Chinese patent application with the application number of CN201610019855.8, which is filed on 1/13/2016 and is entitled "oral quick release probiotic supplement and preparation method".
Technical Field
The invention relates to a probiotic supplement and a preparation method thereof, in particular to a probiotic supplement which is suitable for being rapidly released in oral cavity of children and a preparation method thereof.
Background
The existing solid oral preparation comprises common tablets, capsules, chewable tablets, granules, powder and the like, but the dosage forms are not suitable for children, especially infants. When the tablets are large or must be taken in many pieces, it is difficult for children to swallow or the tablets will stick in the throat or esophagus. Although chewable tablets can be swallowed after chewing without the need for water, they are not suitable for children with poor chewing ability. Granules and powders require water to swallow, and they have the disadvantage of being easily left in the mouth, choking in children.
The probiotics is a living bacterium preparation, can promote the balance of in vivo flora, promote the survival of beneficial bacteria by inhibiting or killing pathogenic bacteria, further regulate gastrointestinal flora, enhance the resistance of intestinal tract, and achieve the effect of treating dyspepsia such as abdominal distension, diarrhea, constipation and the like. The children, especially infants belong to the group with weak immunity, and the probiotic supplement taken by the group can improve the immunity, prevent various diseases, promote digestion and is beneficial to healthy growth. The existing probiotic supplements are usually drinks or dry powders, wherein the drinks need to be taken in a large dose and need to be added with additives such as sweeteners to improve taste, the dry powders need to be taken with water, the requirement on the temperature of the water during preparation is high, and the problem of inaccurate dosage can occur for infants due to the need of parental administration.
Patent WO2007111375A discloses a tablet having a tablet hardness of about 30N to 60N and a moisture content of 3.2% by weight or less, which is obtained by compression molding a mixed powder of probiotics, crystalline cellulose or light anhydrous silicic acid and starch-containing saccharides in a dry state, but the film-forming material has a high hardness and is difficult for children to take and may damage the inside of the oral cavity.
Patent CN1689649A discloses an oral instant preparation containing pullulan and a production method thereof, wherein a matrix mainly comprises the following raw materials in parts by weight: 1-10 parts of a skeleton supporting agent and 1-10 parts of pullulan, the oral instant preparation has better formability, but the probiotics has poor solubility in an aqueous solution, so a suspending agent needs to be added, and the types and the content of various auxiliary materials in the preparation formula can influence the activity of the probiotics, possibly causing the reduction of the efficacy of the probiotics.
WO2013123623A1 discloses an orally disintegrating tablet and a preparation method thereof, wherein the orally disintegrating tablet is prepared by a freeze-drying method, and the components comprise an effective dose of pharmaceutical active ingredient, a skeleton supporting agent, a binder and a suspending agent, wherein the binder consists of pullulan and an auxiliary binder, and the problems of slow disintegration and incomplete dissolution of the freeze-dried orally disintegrating tablet when a large dose of medicine is loaded are solved by using the pullulan and the auxiliary binder in a compounding manner within a specific dosage range. However, the formulation requires the addition of auxiliary binders and suspending agents to increase the drug loading, the taste of the tablets is greatly affected, especially for children, the interest in continuous administration of the supplement is affected, and the activity of probiotics can be affected by pullulan and auxiliary binders.
Accordingly, the present invention overcomes the deficiencies of the prior art and provides a rapid release probiotic supplement and method of preparation that is suitable for use in children.
Disclosure of Invention
It is an object of the present invention to provide a probiotic supplement loaded with a high dose, which disintegrates rapidly in the oral cavity, while having a good taste, and which maintains the viable count of the probiotic, suitable for administration to children, in particular infants.
The invention also aims to provide a preparation method of the probiotic supplement, which overcomes the defects of low survival rate of probiotics, nonuniform content of probiotics in a preparation, low release speed and incapability of industrial production in the preparation process of the probiotic supplement in the prior art.
Thus, in a first aspect the present invention provides a probiotic supplement for immediate release in the mouth suitable for use in children comprising in a unit dose 5-80mg of probiotic bacteria, 6-12mg of a support agent, 6-12mg of pullulan, wherein the unit dose comprises less than 0.2mg of a suspending agent.
The probiotic bacteria of the present invention are selected from one or more species of Bifidobacterium (e.g., bifidobacterium longum), bifidobacterium infantis (Bifidobacterium infantis), bifidobacterium bifidum (Bifidobacterium bifidum), bifidobacterium breve (Bifidobacterium breve), etc.), lactic acid bacteria (Lactobacillus casei), lactobacillus gasseri (Lactobacillus gasseri), lactobacillus rhamnosus (Lactobacillus rhamnous), lactobacillus acidophilus (Lactobacillus acidophilus), streptococcus faecalis (Streptococcus faecalis), streptococcus thermophilus (Streptococcus thermophilus), etc.). Preferably, the probiotics are selected from one or more than two of bifidobacterium longum, bifidobacterium infantis, lactobacillus gasseri, lactobacillus rhamnosus and lactobacillus acidophilus. For probiotic supplements, the formulation thereof needs to contain high content of probiotics in order to exert the activity of the probiotics in vivo, so that the ability to carry higher doses of probiotics in tablets is a problem to be solved by the probiotic supplement. The probiotic supplement of the invention contains 5-80mg of probiotics per unit dose, preferably 40-80mg of probiotics, and more preferably 50-70mg of probiotics.
The supporting agent is selected from mannitol or glycine, and preferably, the supporting agent is mannitol. The probiotic supplement preferably contains 8-10mg of supporting agent in unit dosage, and more preferably 10mg of supporting agent in unit dosage.
Preferably, the unit dose of the probiotic supplement of the invention comprises pullulan in an amount of 8-10mg, more preferably 10mg.
Since the suspending agent has a thickening and suspending effect, a high content of the suspending agent is often added when a large amount of active ingredient needs to be loaded in the formulation, but the suspending agent gives a sticky mouth feel and an unpleasant taste after being dissolved in the oral cavity, and an excessive amount of xanthan gum affects the disintegration time of the tablet, and thus the amount of xanthan gum needs to be controlled. The probiotic supplement of the present invention comprises in unit dose less than 0.2mg, preferably less than 0.1mg suspending agent in unit dose. In a more preferred embodiment of the invention, the probiotic supplement does not contain a suspending agent. The suspending agent of the present invention is preferably xanthan gum.
In one embodiment of the present invention, the probiotic supplement further comprises a sweetener, and the unit dose of the probiotic supplement further comprises less than 0.3mg of the sweetener, preferably, the unit dose of the probiotic supplement further comprises less than 0.2mg of the sweetener, and more preferably, the unit dose of the probiotic supplement further comprises less than 0.1mg of the sweetener. The sweetener is selected from sucralose or aspartame, and more preferably sucralose.
In one embodiment of the present invention, the probiotic supplement further comprises a flavoring agent, wherein the content of the flavoring agent can be adjusted by a person skilled in the art according to the required taste, and the flavoring agent can be strawberry essence, banana essence, milk essence, etc.
In one embodiment of the invention, the unit dosage of the probiotic supplement consists of 5-80mg of probiotics, 6-12mg of supporting agent, 6-12mg of pullulan, less than or equal to 0.3mg of sweetening agent and flavoring agent.
The probiotic supplement suitable for being rapidly released in the oral cavity of children can also comprise mecobalamin, vitamin B1, vitamin B2, vitamin B12, vitamin A, vitamin D, vitamin E, vitamin B6, vitamin C, vitamin E nicotinate, vitamin K, amino acids, carotene, inositol, nicotinic acid, taurine, and trace elements such as calcium, iron, zinc, magnesium and the like.
The invention also provides a preparation method of the probiotic supplement which is suitable for being rapidly released in the oral cavity of children, and the raw materials of the probiotic supplement comprise 1-16% of probiotics, 1.2-2.4% of supporting agent, 1.2-2.4% of pullulan and the balance of water according to mass percentage.
In the raw materials, the probiotics are preferably powder, more preferably, the raw materials comprise 8-16% of the probiotics by mass percent, and more preferably, the raw materials comprise 10-12% of the probiotics by mass percent.
In the raw materials of the present invention, the preferable supporting agent is 1.5 to 2.4% by mass, and more preferably 2% by mass.
In the raw materials of the invention, the preferable pullulan accounts for 1.5-2.4% by mass, and the preferable pullulan accounts for 2% by mass.
In one embodiment of the present invention, the raw material comprises less than 0.04% by mass of the suspending agent, more preferably, the raw material comprises less than 0.02% by mass of the suspending agent, and most preferably, the raw material does not comprise the suspending agent.
In one embodiment of the present invention, the raw material further comprises a sweetener, and the sweetener is less than 0.06%, preferably less than 0.05%, and most preferably less than 0.02% by mass. The sweetener is selected from sucralose or aspartame, and more preferably sucralose.
In one embodiment of the invention, the raw materials further comprise a flavoring agent, the mass percentage of the flavoring agent can be adjusted by a person skilled in the art according to the required taste, and the flavoring agent can be strawberry essence, banana essence, milk essence and the like.
The preparation method of the probiotic supplement suitable for being rapidly released in the oral cavity of children comprises the following steps: (1) Mixing probiotic bacteria, supporting agent and pullulan, adding water, stirring, and emulsifying; (2) Injecting the emulsified material into a mold, pre-freezing, and freeze-drying to obtain the probiotic supplement. The preparation method of the probiotic supplement has an emulsification process, so that probiotics can be uniformly dispersed, the content of the finally obtained supplement is uniform, and the use of a suspending agent can be reduced.
In one embodiment of the invention, the step (1) is to take probiotics, a supporting agent, pullulan and one or more of a suspending agent, a sweetening agent and a flavoring agent, dry mix them, add water, stir them evenly and emulsify them.
The step (1) of the preparation method of the probiotic supplement adopts a shear emulsification method, preferably, the shear rate of the shear emulsification method is 1000-6000rpm, and more preferably, 2000-5000rpm. The emulsifying time of the shearing emulsification method is 1-30min, preferably 5-10min.
In the step (1) of the preparation method of the probiotic supplement, a degassing step is further included after emulsification, preferably, the degassing is vacuum degassing for 1-20min, preferably 2-10min.
The preparation method of the probiotic supplement disclosed by the invention is characterized in that the mold in the step (2) is an aluminum-plastic bubble cap plate.
The pre-freezing in the step (2) of the preparation method of the probiotic supplement is pre-freezing at-70 to-40 ℃ for 1 to 20min, preferably 2 to 10min.
The preparation method of the probiotic supplement comprises the following steps of (2): keeping at-25 deg.C to-10 deg.C for 1-5h, then raising to 10-30 deg.C within 1-5h, and keeping for 1-5h; preferably, the freeze-drying is carried out at-20 ℃ for 2h, followed by a rise to 20 ℃ within 3h, which is maintained for 2h.
In a more specific embodiment of the present invention, the preparation method of the probiotic supplement comprises:
(1) Weighing probiotics, a supporting agent and pullulan, dry-mixing, adding water, stirring uniformly, shearing and emulsifying for 5-10min at 2000-5000rpm for the first time, and vacuum degassing the uniformly emulsified material for 2-10min;
(2) Injecting the material obtained in the step (1) into a bubble hole of an aluminum-plastic bubble-cap plate, pre-freezing for 2-10min at-70 to-40 ℃, and freeze-drying to obtain the probiotic supplement, wherein the freeze-drying comprises the following steps: keeping at-25 deg.C to-10 deg.C for 1-5h, then raising to 10-30 deg.C within 1-5h, and keeping for 1-5h.
In a further aspect of the invention there is provided the use of the probiotic supplement in the preparation of a dietary and/or nutritional supplement for children.
In a further aspect, the invention provides the use of the probiotic supplement in the preparation of a supplement for improving immunity.
In a further aspect, the invention provides the use of the probiotic supplement in the manufacture of a supplement for promoting gastrointestinal digestion.
The probiotic supplement released quickly in the oral cavity can load high-dose probiotics and disintegrate quickly in the oral cavity, has good mouthfeel, is high in survival rate of the probiotics in the preparation, and is suitable for children, particularly infants to take.
The present invention is not limited to the particular methodology, protocols, and protocols described herein as these may vary. Furthermore, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention.
Unless defined differently, all technical and scientific terms and any abbreviations herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the illustrative methods, devices, and materials are described herein.
The terms of the present invention have meanings commonly used in the art unless otherwise specified.
The term "rapid release" in the context of the present invention means that the time for disintegration or dissolution of the supplement in the mouth is less than 20s, more preferably less than 10s, and most preferably less than 5s.
The term "probiotic supplement" in the present invention refers to a dietary or nutritional supplement containing probiotics.
The term "child" in the present invention means a child of 0 to 10 years old, preferably 0 to 5 years old, most preferably 0 to 3 years old.
Detailed Description
Example 1
Prescription:
lactobacillus rhamnosus 50.00g
Pullulan 10.00g
Mannitol 10.00g
0.25g of sucralose
Strawberry essence 1000ul
428.75g of purified water
A total of 500.00g
Making into 1000 pieces
The preparation process comprises the following steps:
(1) Weighing lactobacillus rhamnosus, pullulan, mannitol, sucralose and strawberry essence according to the formula amount, placing the materials into a proper container, mixing the materials evenly, adding purified water and stirring the mixture evenly for later use;
(2) Adding strawberry essence (measured according to volume), fixing the volume to the amount of the prescription, stirring uniformly, and carrying out shearing emulsification at the shearing rate of 1000rpm for 2min;
(3) Vacuum degassing the material obtained in the step (2) for 10min;
(4) Subpackaging at a volume of 0.5 ml/tablet, and respectively injecting into the cells of the aluminum-plastic bubble cap plate;
(5) Pre-freezing the material obtained in the step (4) in a refrigerator at the temperature of-40 ℃ for 10min;
(6) Freeze-drying the material obtained in the step (5), wherein the specific conditions are as follows: setting the initial temperature of freeze drying at-20 deg.c, freeze drying the pre-frozen eye in a freeze drying oven for 4 hr to raise from-20 deg.c to 20 deg.c within 3 hr, and maintaining at 20 deg.c for 3 hr.
(7) And (4) taking the blister plate out of the freeze dryer, and carrying out heat-seal packaging by using an aluminum plastic bag.
Example 2
Prescription:
lactobacillus rhamnosus 40.00g
Pullulan 12.00g
Mannitol 12.00g
0.25g of sucralose
Strawberry essence 1000ul
425.75g of purified water
A total of 500.00g
Making into 1000 pieces
The preparation process comprises the following steps:
(1) Weighing lactobacillus rhamnosus, pullulan, mannitol, sucralose and strawberry essence according to the formula amount, putting the materials into a proper container, mixing the materials evenly, adding purified water and stirring the materials evenly for later use;
(2) Adding strawberry essence (measured according to volume), fixing the volume to the amount of the prescription, stirring uniformly, and performing shearing emulsification at the shearing rate of 5000rpm for 1min;
(3) Vacuum degassing the material obtained in the step (2) for 5min;
(4) Subpackaging at a volume of 0.5 ml/tablet, and respectively injecting into the cells of the aluminum-plastic bubble cap plate;
(5) Pre-freezing the material obtained in the step (4) in a refrigerator at-50 ℃ for 5min;
(6) Freeze-drying the material obtained in the step (5), wherein the specific conditions are as follows: setting the initial temperature of freeze drying to-25 deg.c, freeze drying the pre-frozen soaked eye in a freeze drying oven for 4 hr, raising the temperature from-25 deg.c to 25 deg.c within 3 hr, maintaining at 25 deg.c for 1 hr.
(7) And taking the blister plate out of the freeze dryer, and carrying out heat sealing packaging by using an aluminum plastic bag.
Example 3
Prescription:
lactobacillus rhamnosus 80.00g
6.00g of pullulan
Mannitol 6.00g
Sucralose 0.25g
Strawberry essence 1000ul
Purified Water 407.75g
A total of 500.00g
Making into 1000 pieces
The preparation process comprises the following steps:
(1) Weighing lactobacillus rhamnosus, pullulan, mannitol, sucralose and strawberry essence according to the formula amount, putting the materials into a proper container, mixing the materials evenly, adding purified water and stirring the materials evenly for later use;
(2) Adding strawberry essence (measured according to volume), fixing the volume to the amount of the prescription, stirring uniformly, and carrying out shearing emulsification at the shearing rate of 2000rpm for 10min;
(3) Vacuum degassing the material obtained in the step (2) for 10min;
(4) Subpackaging at a volume of 0.5 ml/sheet, and respectively injecting into bubble holes of an aluminum-plastic bubble cap plate;
(5) Pre-freezing the material obtained in the step (4) in a refrigerator at the temperature of 50 ℃ below zero for 5min;
(6) And (5) freeze-drying the material obtained in the step (5), wherein the specific conditions are as follows: setting the initial temperature of freeze drying at-20 deg.c, freeze drying the pre-frozen eye in a freeze drying oven for 5 hr to raise from-20 deg.c to 20 deg.c within 4 hr, maintaining at 25 deg.c for 1 hr.
(7) And (4) taking the blister plate out of the freeze dryer, and carrying out heat-seal packaging by using an aluminum plastic bag.
Comparative examples 1 to 3
The recipe and the process are shown in the following table.
TABLE 1 formulations and preparation of comparative examples 1-3
Figure BDA0003839674770000081
Figure BDA0003839674770000091
Comparative examples 1-3 were prepared by the same procedure as in example 1.
Comparative example 4
Prescription:
lactobacillus rhamnosus 50.00g
Pullulan 10.00g
Mannitol 10.00g
0.25g of sucralose
Strawberry essence 1000ul
429.75g of purified water
A total of 500.00g
Making into 1000 pieces
The preparation process comprises the following steps:
(1) Weighing lactobacillus rhamnosus, pullulan, mannitol, sucralose and strawberry essence according to the formula amount, putting the materials into a proper container, mixing the materials evenly, adding purified water and stirring the materials evenly for later use;
(2) Adding strawberry essence (measured according to volume), fixing the volume to the prescription amount, and uniformly stirring;
(3) Vacuum degassing the material obtained in the step (2) for 10min;
(4) Subpackaging at a volume of 0.5 ml/tablet, and respectively injecting into the cells of the aluminum-plastic bubble cap plate;
(5) Pre-freezing the material obtained in the step (4) in a refrigerator at the temperature of-40 ℃ for 10min;
(6) Freeze-drying the material obtained in the step (5), wherein the specific conditions are as follows: setting the initial temperature of freeze drying at-20 deg.C, placing the pre-frozen eye in a freeze drying oven, freeze drying for 4 hr, heating from-20 deg.C to 20 deg.C within 3 hr, and maintaining at 20 deg.C for 3 hr.
(7) And (4) taking the blister plate out of the freeze dryer, and carrying out heat-seal packaging by using an aluminum plastic bag.
Example 4 probiotic supplement mouthfeel testing
The probiotic supplements prepared in examples 1-3 and comparative examples 1-4 were subjected to mouth feel tests.
The experimental method comprises the following steps: the package is opened, the freeze-dried tablet is taken out and placed on the tongue without chewing, and the tablet is taken without water until all suspended matters in the oral cavity are spitted out after the tablet is completely disintegrated. And 3 testers evaluated after tasting, and the evaluation was carried out by taking the average grade. The evaluation grades are classified as follows:
1) "+++++": the product can be dissolved in the mouth, the disintegration time is less than 10 seconds, and the product has no lumps, no gravel feeling and moderate sweetness.
2) "++++": the product can be dissolved in the mouth, the disintegration time is less than 20s after 10 seconds, no lumps and no gravel feeling exist, and the sweetness is moderate.
3) "+++": the grade is given by any 1 item of four items of disintegration time, lump, gritty feeling and sweetness.
4) "++": any 2-3 items of four items of disintegration time, lumps, gritty feeling and sweetness are classified as the grade.
5) "+": the oral liquid is not crumbled in the mouth, is in the shape of a lump, has strong sense of gravel and excessive sweetness.
The experimental results are as follows:
TABLE 2 results of the experiment
Sample (I) Rating of evaluation
Example 1 +++++
Example 2 +++++
Example 3 +++++
Comparative example 1 +++
Comparative example 2 ++
Comparative example 3 +++
Comparative example 4 ++
Example 5 probiotic supplements probiotics were subjected to live bacteria survival experiments
Live bacteria survival experiments were performed using examples 1-3 and comparative examples 1-4.
The experimental method comprises the following steps: according to the feeding calculation, one freeze-dried tablet contains 50 hundred million probiotics per tablet, the viable count of the probiotics contained in 1 freeze-dried tablet is detected according to the method, and the survival rate =1 viable count of the freeze-dried tablets/50 hundred million multiplied by 100 percent. The experimental results are as follows:
TABLE 3 results of the experiment
Figure BDA0003839674770000101
Figure BDA0003839674770000111
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents and the like included within the spirit and scope of the present invention.

Claims (10)

1. An intraorally rapidly released probiotic supplement, characterized in that the probiotic supplement comprises 5-80mg of probiotics, 6-12mg of a supporting agent and 6-12mg of pullulan in unit dose, and comprises less than 0.2mg of a suspending agent in unit dose.
2. The oral fast release probiotic supplement of claim 1, wherein said probiotic is selected from the group consisting of one or more of bifidobacterium species, bifidobacterium bifidum, bifidobacterium breve, lactobacillus species, lactobacillus gasseri, lactobacillus rhamnosus, lactobacillus acidophilus, streptococcus faecalis, and streptococcus thermophilus.
3. The oral rapid release probiotic supplement of claim 1, wherein the probiotic supplement comprises 40-80mg of probiotic per unit dose.
4. The oral rapid release probiotic supplement of claim 1, wherein the supporting agent is selected from mannitol or glycine.
5. The oral rapid release probiotic supplement of claim 1, wherein the probiotic supplement comprises a unit dose comprising less than 0.1mg of suspending agent per unit dose.
6. The intraoral rapid release probiotic supplement of claim 5, wherein the probiotic supplement does not contain a suspending agent.
7. The oral fast release probiotic supplement of any of claims 1 to 6, wherein the probiotic supplement further comprises less than 0.3mg per unit dose of sweetener.
8. A preparation method of a probiotic supplement capable of being rapidly released in an oral cavity is characterized in that raw materials comprise 8-16% of probiotics, 1.2-2.4% of a supporting agent, 1.2-2.4% of pullulan and the balance of water according to mass percentage.
9. The method of preparing an intraorally rapid release probiotic supplement of claim 8, comprising the steps of:
(1) Mixing probiotic bacteria, supporting agent and pullulan, adding water, stirring, and emulsifying;
(2) Injecting the emulsified material into a mold, pre-freezing, and freeze-drying to obtain the probiotic supplement.
10. The method for preparing an intraoral rapid release probiotic supplement according to claim 9, characterized in that the emulsification in step (1) is performed by a shear emulsification method, preferably, the shear rate of the shear emulsification method is 1000-6000rpm, and the emulsification time is 1-30min.
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