CN110917174A - Oral probiotic capsule for regulating balance of female vaginal flora and preparation method thereof - Google Patents
Oral probiotic capsule for regulating balance of female vaginal flora and preparation method thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/724—Cyclodextrins
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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
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
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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
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61K36/815—Lycium (desert-thorn)
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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention provides an oral probiotic capsule for regulating the balance of female vaginal flora and a preparation method thereof. The probiotic capsule comprises 60-80% of composite probiotics, 20-40% of prebiotics and 0-20% of pharmacological auxiliary materials; the composite probiotics at least comprise bacillus coagulans XP, and also comprise any one or more of lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus crispatus, lactobacillus malus and leuconostoc cremoris; the prebiotics are one or more of xylo-oligosaccharide, larch arabinogalactan, soybean titanium powder, cyclodextrin and fruit and vegetable enzyme powder. The preparation process comprises the following steps: preparing probiotic fermentation bacteria powder, mixing the ingredients, drying, crushing and filling. The product has the effects of sustained release, long effective time, strong pertinence, synergistic antibacterial effect, and relieving inflammation and endocrine disturbance caused by female private flora disturbance.
Description
Technical Field
The present invention relates to the field of microbial preparations; in particular to an oral probiotic slow-release capsule preparation which takes the female vagina as a target and is used for adjusting the flora imbalance and a preparation method thereof.
Background
The probiotic is orally administered, and has effects of regulating intestinal flora, inhibiting pathogenic bacteria reproduction, preventing digestive tract diseases, enhancing immunity, supplementing nutrition, improving water environment, removing toxin, and relieving inflammation. Probiotics are widely used in food and health care products. At present, most of probiotic products in the market are liquid preparations, solid granules, tablets, granules and the like, and the market gap of finished capsule products is large. Compared with other preparations, the capsule has simple preparation process, and the properties of probiotics are not easy to change in the preparation process, but the efficacy of the existing probiotic capsule in the market is similar to that of probiotic products of other dosage forms, the capsule can be quickly digested by gastrointestinal tracts after being taken orally, the effect of regulating the balance of flora stays in the gastrointestinal tracts at most, and the capsule can be quickly decomposed and absorbed, and has little health care effect. Therefore, in the prior art, probiotics are prepared into capsules, the efficacy positioning of the capsules is generally aimed at gastrointestinal tract nursing, treatment of other parts which cannot be touched, and the understanding and the resolving of pain points are not accurate enough.
Modern women have high living and working pressure and irregular diet and work, which often cause endocrine dyscrasia and greatly reduce the disease resistance of genital systems. Especially female vagina is a private position, and various microorganisms are stored in the vagina, including aerobic bacteria such as corynebacterium, enterococcus, nonhemolytic streptococcus and the like, and facultative anaerobe such as lactobacillus, gardnerella and escherichia coli and the like. The anaerobic bacteria comprise digestive coccus, digestive streptococcus, bacteroides and the like, and also comprise mycoplasma and candida, the vagina forms a harmonious microecological balance with the flora, and diseases such as bacterial infection, fungal infection and the like are very easy to occur in case of short nursing. Vaginitis and other diseases in women are all related to dysbacteriosis, and subhealth or disease patients often need to be conditioned by taking antibiotics and externally using anti-inflammatory and antibacterial medicines.
Probiotic health-care products aiming at the resistance and flora regulation of the female vagina or reproductive system have huge gaps in the market. However, the properties of the probiotics are easily influenced by environmental factors, so that the preparation process is not suitable for over-processing, and the problems of stability and timeliness of the finished preparation after entering into the body need to be considered in the preparation process. Therefore, it is necessary to develop a probiotic preparation which is easy to prepare, has long time-efficiency in physical performance, and can effectively provide targeted treatment and regulation effects to the target point.
Disclosure of Invention
The invention aims to provide a compound probiotic capsule which can achieve a slow release effect in vivo, has better timeliness in vivo and more accurate target point pertinence and is suitable for regulating the female vaginal flora imbalance.
In order to achieve the purpose, the invention adopts the following technical scheme:
firstly, the invention provides an oral probiotic capsule for regulating the balance of female vaginal flora, which comprises 60-80% of composite probiotics, 20-40% of prebiotics and 0-20% of pharmacological auxiliary materials by mass fraction; the composite probiotics at least comprise bacillus coagulans XP, and also comprise any one or more of lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus crispatus, lactobacillus malus and leuconostoc cremoris; the prebiotics are one or more of xylo-oligosaccharide, larch arabinogalactan, soybean titanium powder, cyclodextrin and fruit and vegetable enzyme powder; each capsule contains 200-800 hundred million CFU of composite probiotics.
The invention originally comprises the following steps: the applicant screened a newly screened bacillus coagulans xp (bacillus coaguluns xp) strain, which has been deposited with the chinese type culture collection; in previous researches, the applicant found that the bacillus coagulans XP has obvious effects of improving the immunity of livestock and strengthening physique when being used as a feed additive (see the applied patent application document 201810373808.2). Through research, the strain also has the characteristics of regulating the flora balance, improving the flora disadvantage and promoting the propagation of beneficial flora in a complex microbial environment. The strain is sporulated lactic acid bacteria, can better reach a vaginal microenvironment through strong gastric acid resistance of spores, and forms a dominant flora by field planting, so that the vaginal flora is balanced, and the inflammation incidence is reduced. Therefore, the bacillus coagulans XP is mainly adopted to form the composite probiotics by matching with other beneficial bacteria with related functions, and the composite probiotics is mainly aimed at the female reproductive system, particularly the aspects of conditioning the unbalance of vaginal flora and enhancing the barrier function of vaginal mucosa.
The strains compounded with bacillus coagulans XP are as follows:
lactobacillus reuteri: can secrete Roiximab, has broad-spectrum antibacterial property, and can relieve VVC, BV and the like; repairing vaginal mucosa, regulating vaginal flora balance, and enhancing self-cleaning and self-free function.
Lactobacillus rhamnosus: the intestinal tract digestion environment of animals is tolerated, the intestinal tract is planted, the diarrhea is relieved, the intestinal flora is adjusted, the intestinal mucosa barrier is enhanced, and the toxin is discharged.
Lactobacillus acidophilus: antagonizing pathogenic bacteria; regulating flora in stomach and intestinal tract.
Lactobacillus crispatus: high efficiency of vaginal epithelial cell adhesion; improving female reproductive health.
Lactobacillus equi: produces macromolecular biological polysaccharide outside cells, can promote the growth of other probiotics in intestinal tracts, and simultaneously regulates immunity and stabilizes blood pressure.
Leuconostoc mesenteroides butterfat subspecies: can stimulate the growth of normal flora in intestinal tract. Leuconostoc mesenteroides has antagonistic effect on common pathogenic bacteria such as Shigella, Salmonella, Staphylococcus aureus, etc.
The strains have the advantages of antagonizing pathogenic bacteria, enhancing mucosal barrier, promoting beneficial bacteria propagation and the like, and the synergistic strengthening effect is generated by combining and matching the probiotics and the bacillus coagulans XP, so that the effect is obvious. For example: the lactobacillus reuteri is matched with three bacteria of rhamnose bacillus and lactobacillus crispatus, and the inhibition effect on typical vaginitis initiating bacteria such as escherichia coli, candida albicans or staphylococcus aureus is obviously improved.
On the other hand, prebiotics, which are usually used as a dietary supplement, beneficially affect the host by selectively stimulating the growth and activity of one or a small number of bacteria in a colony to enhance the action of that colony, and they simply stimulate the growth of a beneficial bacterial flora. Therefore, on the basis of the synergistic effect of the compound probiotics, the efficacy of the preparation can be greatly enhanced by compounding the prebiotics. Prebiotics useful in the present invention include these:
and (3) xylo-oligosaccharide: the enzyme for hydrolyzing xylo-oligosaccharide is not contained in the gastrointestinal tract of a human body, and the xylo-oligosaccharide can directly enter the large intestine after being ingested and can be rapidly utilized by probiotics in the body, so that the flora number of the probiotics is increased.
Larch arabinogalactan: has antioxidant activity and has good scavenging ability for free radicals such as DHPP, ABTS and the like. Has certain immunological competence.
Soybean titanium powder: can be directly absorbed in small intestine without intestinal digestion, contains multiple bioactive peptides, and has effects of resisting oxidation, reducing blood sugar, etc.
Cyclodextrin: as an auxiliary material, the composition can improve the dissolution and bioavailability of the medicine and enhance the emulsifying and moisture-proof capabilities.
Fruit and vegetable enzyme powder: the semen plantaginis husk can regulate intestine and stomach, promote digestion and absorption, and improve intestine and stomach health.
The prebiotics can supplement raw materials for probiotics in intestinal tracts and probiotics covered by the formula, so that the prebiotics can better grow and colonize the intestinal tracts, and assist in improving the vaginal flora environment and the large and small intestinal flora environment.
Further, the Bacillus coagulans XP is deposited in the China center for type culture Collection in 2017, 12 and 25 months, and the preservation registration number is CCTCC NO: M2017836. The bacillus coagulans XP (bacillus coagulans XP) belongs to the bacillus in the strain classification, is a gram-positive bacterium, and has bacterial colonies which exist singly or in pairs and rarely form a straight-chain arrangement; the cells are rod-shaped, have terminal spores and no flagellum and form endospores; the size of the single thallus is 4-6 μm in length and 0.4-0.9 μm in width.
The 16S rDNA sequence of the bacillus coagulans XP (Bacillus coagulans XP) is as follows: gctggctccgtaaaggttacctcaccgacttcgggtgttacaaactctcgtggtgtgacgggcggtgtgtacaaggcccgggaacgtattcaccgcggcatgctgatccgcgattactagcgattccggcttcatgcaggcgggttgcagcctgcaatccgaactgggaatggttttctgggattggcttaacctcgcggtctcgcagccctttgtaccatccattgtagcacgtgtgtagcccaggtcataaggggcatgatgatttgacgtcatccccaccttcctccggtttgtcaccggcagtcaccttagagtgcccaactgaatgctggcaactaaggtcaagggttgcgctcgttgcgggacttaacccaacatctcacgacacgagctgacgacaaccatgcaccacctgtcactctgtcccccgaaggggaaggccctgtctccagggaggtcagaggatgtcaagacctggtaaggttcttcgcgttgcttcgaattaaaccacatgctccaccgcttgtgcgggcccccgtcaattcctttgagtttcagccttgcggccgtactccccaggcggagtgcttaatgcgttagctgcagcactaaagggcggaaaccctctaacacttagcactcatcgtttacggcgtggactaccagggtatctaatcctgtttgctccccacgctttcgcgcctcagcgtcagttacagaccagagagccgccttcgccactggtgttcctccacatctctacgcatttcaccgctacacgtggaattccactctcctcttctgcactcaagcctcccagtttccaatgaccgcttgcggttgagccgcaagatttcacatcagacttaagaagccgcctgcgcgcgctttacgcccaataattccggacaacgcttgccacctacgtattaccgcggctgctggcacgtagttagccgtggctttctggccgggtaccgtcaaggcgccgccctgttcgaacggcacttgttcttccccggcaacagagttttacgacccgaaggccttcttcactcacgcggcgttgctccgtcagactttcgtccattgcggaagattccctactgctgcctcccgtaggagtttgggccgtgtctcagtcc caatgtggccgatcaccctctcaggtcggctacgcatcgttgccttggtgagccgttaccccaccaacaagctaatgcgccgcgggcccatctgtaagtgacagcagaagccgtctttcctttttcctccatgcggaggaaaaaactatccggtattagccccggtttcccggcgttatcccgatcttacaggcaggttgcccacgtgttactcacccgtccgccgctaaccttttaaaagcaagcttttaaaaggtccgcacgacttgc are provided.
Furthermore, in order to enhance the therapeutic performance of the probiotic capsule, one or more of medicinal powder such as angelica, medlar, peach gum, bighead atractylodes rhizome and the like can be added into the raw materials as pharmacological auxiliary materials. Wherein, the angelica has the efficacies of treating abdominal distension and pain, replenishing blood and qi, improving irregular menstruation and the like; fructus Lycii has effects of enhancing immunity, resisting aging, and relieving fatigue; the peach gum has the effects of lubricating, reducing pathogenic fire and expelling toxin; atractylodis rhizoma has effects of invigorating spleen, invigorating qi, eliminating dampness, promoting diuresis, and stopping sweating. The medicinal materials have pharmacological acid resistance and enzymolysis resistance, can protect the stability of probiotics and prebiotics in vivo to a certain extent after being mixed with the probiotics and prebiotics, and have the effects of conditioning and enhancing the absorption of gastrointestinal tracts.
Furthermore, the capsule shell of the capsule provided by the invention is made of high molecular polymer material with slow release performance; the capsule shell can be made of any one of gelatin, hydroxypropyl methylcellulose capsules, starch capsules and seaweed capsules; hydroxypropyl methylcellulose capsules and starch capsules are preferably used. The capsule shell can be No. 0 or No. 1, and needs to be opaque. The material has the effects of acid corrosion resistance, enzymolysis resistance, strong adsorbability and slow release, and can protect probiotics and prebiotics from being decomposed in oral cavity, stomach and upper section of digestive tract to a certain extent, and the retention time in human body is too short to reach reproductive system.
The invention also provides a preparation method of the oral probiotic capsule for regulating the balance of female vaginal flora, which is completed in a GMP workshop and comprises the following steps:
(1) preparing probiotic fermentation bacteria powder: centrifuging various probiotic fermentation liquid which form the composite probiotics at the speed of 100-500 rpm and the temperature of 4-10 ℃, separating solid from liquid, removing supernatant, collecting solid substances of the probiotics, freeze-drying the solid substances for 2-16 hours at the temperature of-15-0 ℃, and storing freeze-dried probiotic fermentation powder at the temperature of 0-10 ℃ for later use;
(2) mixing the ingredients: mixing various probiotic fermentation bacteria powder, prebiotics powder and medicinal auxiliary material powder which form the composite probiotic in proportion, and fully mixing and stirring at room temperature under the condition that the environmental humidity is 5-15%;
(3) drying, crushing and filling: and drying the mixed solid powder material at 18-40 ℃, crushing until the granularity is not more than 100 mu m to obtain the composite probiotic powder, filling the composite probiotic powder into a capsule shell, and storing at a cool place at room temperature.
The probiotic capsule prepared by the steps is stored at a cool place at room temperature, and the effective period is 6 months.
Preferably, in the step (1) of freeze-drying, one or more of glycerol, skim milk, VC, and the like are further added to the probiotic solid substance as a freeze-drying protective agent, and the addition amount of the freeze-drying protective agent is 0.5-2% of the weight of the probiotic solid substance.
Preferably, the probiotic fermentation liquor selected in the step (1) has a density of 2-20 g/L and an active probiotic content of 100-400 billion CFU/L.
Preferably, in the drying process in the step (3), the mixing and stirring speed is 50-200 rpm, and the duration is 10-60 minutes until the water content of the powder is less than 0.05%. The crushing process is carried out by adopting a crusher, and the crushing rotating speed is 13000-20000 rpm.
The probiotic content is measured by adopting a plate counting method, and the detection culture medium is a universal MRS culture medium.
The plate counting method comprises the following steps: pouring 15-20 mL of detection medium into each plate in advance, after cooling and solidifying, weighing 0.1-1 g of probiotics (powder), dissolving in 100mL of sterile distilled water, sequentially diluting in a gradient manner, and selecting 10-8、10-9And 10-10Taking 100 mul of sample homogenized solution of three dilutions, respectively sucking by a micropipette, inoculating on a culture medium, and coating by using an L-shaped or triangular glass rod; aerobic culture is carried out for 24h at the constant temperature of 37 ℃, culture dishes with the colony number ranging from 30 to 300 are selected for counting, the dilution times are converted, and the calculation result is expressed by hundred million/g (three parallel repetitions are carried out simultaneously, and the result is averaged).
Wherein, the detection culture medium adopts a universal MRS culture medium, and comprises the following components:peptone10.0g, beef extract 10.0g, yeast extract 5.0g, diammonium hydrogen citrate [ (NH4)2HC6H5O7]2.0g, 20.0g of glucose (C6H12O 6. H2O), Tween 801.0mL, sodium acetate (CH3 COONa.3H 2O)5.0g, dipotassium hydrogen phosphate (K2HPO 4.3H 2O)2.0g, magnesium sulfate (MgSO 4.7H 2O)0.58g, manganese sulfate (MnSO 4. H2O)0.25g, agar 18.0g, 1000 mL of distilled water, and pH 6.2-6.6.
The compound probiotic capsule provided by the invention has the following advantages: (1) the combination of the contained multiple probiotic strains has strong pertinence and a synergistic antibacterial effect, can effectively relieve inflammation and endocrine dyscrasia caused by female private flora dyscrasia, improves the balance of intestinal flora and keeps the female vagina healthy; (2) the capsule shell is made of a material with strong gastric acid resistance and enzymolysis resistance, so that more effective viable bacteria can reach the intestinal tract and enter the reproductive system to the internal environment of the private part of the female, and the efficacy of the probiotic is improved.
Detailed Description
The technical solution of the present invention is further illustrated by the following examples, but the scope of the present invention is not limited to the implementation of the following examples.
Example 1
An oral probiotic capsule health product for regulating balance of female vaginal flora comprises the following components in percentage by mass: (1) compounding probiotics: 15% of lactobacillus reuteri, 15% of lactobacillus acidophilus, 14% of bacillus coagulans XP, 8% of lactobacillus malus, 8% of leuconostoc mesenteroides butterfat subspecies; (2) prebiotics: 7% of xylo-oligosaccharide, 7% of larch arabinogalactan, 5% of cyclodextrin and 5% of fruit and vegetable enzyme powder; (3) auxiliary materials: 5% of angelica, 5% of medlar, 3% of peach gum and 3% of bighead atractylodes rhizome.
The preparation method of the probiotic capsule comprises the following steps:
(1) preparing probiotic fermentation bacteria powder: centrifuging five probiotic fermentation liquids at low temperature of 4 deg.C at 120rpm, respectively, discarding supernatant, collecting thallus, freeze drying, adding skimmed milk (lyophilized protectant) 1.5% of thallus weight, drying at-10 deg.C for 12 hr. Drying to obtain zymophyte powder, and storing at 4 deg.C for use.
Wherein the indexes of the five probiotics before centrifugation are as follows:
TABLE 1 probiotic indices before centrifugation
(2) Mixing the probiotic fermentation bacteria powder with the prebiotics powder: mixing and stirring the five probiotic powder and the prebiotics according to the weight percentage, wherein the stirring speed is 150rpm, carrying out secondary drying at 28 ℃ for 15min until the water content is 0.02%, and then crushing until the particle fineness is less than or equal to 100 mu m to obtain the composite probiotic powder.
(3) Filling capsules to prepare finished products: filling the composite probiotic powder into a hydroxypropyl methyl cellulose capsule shell to obtain a probiotic capsule product.
(4) And detecting the viable count by using a flat plate counting method, wherein the viable count of the composite capsule is 210 hundred million CFU/capsule, the type of the capsule is No. 0, and the filling amount of each capsule is 0.4g and is marked as A1.
The probiotic capsule is administered orally, one granule per day. The product can be stored at room temperature.
Example 2
An oral probiotic capsule health product for regulating balance of female vaginal flora comprises the following components in percentage by mass: (1) compounding probiotics: 15% of lactobacillus reuteri, 15% of bacillus coagulans xp, 10% of lactobacillus rhamnosus, 10% of lactobacillus equi, 10% of leuconostoc mesenteroides butterfat subspecies; (2) prebiotics: 15% of xylo-oligosaccharide and 10% of soybean titanium powder; (3) auxiliary materials: 5% of angelica, 5% of medlar and 5% of bighead atractylodes rhizome.
The preparation method of the probiotic capsule comprises the following steps:
(1) preparing probiotic fermentation bacteria powder: centrifuging five probiotic fermentation liquids at low temperature of 500rpm and 10 ℃, respectively, removing supernatant, collecting thallus, freeze-drying, adding Vc (freeze-drying protective agent) with the weight of 2% of the thallus, and drying at-10 ℃ for 14 h. Drying to obtain zymophyte powder, and storing at 4 deg.C for use.
Wherein the indexes of the five probiotics before centrifugation are as follows:
TABLE 2 probiotic indices before centrifugation
(2) Mixing the probiotic fermentation bacteria powder with the prebiotics powder: mixing and stirring the five probiotic powder, the prebiotics and the auxiliary materials according to the weight percentage, wherein the stirring speed is 150rpm, and performing secondary drying at 28 ℃ for 15min, and the water content is 0.02%. And crushing the mixture to the particle fineness of less than or equal to 100 mu m to obtain the composite probiotic powder.
(3) Filling capsules to prepare finished products: filling the composite probiotic powder into the starch capsule shell to obtain the composite probiotic capsule product.
(4) And detecting the viable count by using a flat plate counting method, wherein the viable count of the composite capsule is 500 hundred million CFU/capsule, the type of the capsule is 0, and the filling amount of each capsule is 0.4g and is marked as A2.
The probiotic capsule is administered orally, one granule per day. The product can be stored at room temperature.
Example 3
An oral probiotic capsule health product for regulating balance of female vaginal flora comprises the following components in percentage by mass: 14% of bacillus coagulans XP, 14% of lactobacillus reuteri, 12% of lactobacillus rhamnosus, 10% of lactobacillus acidophilus, 10% of lactobacillus crispatus, 10% of lactobacillus malus and 10% of leuconostoc mesenteroides butterfat subspecies; 5% of xylo-oligosaccharide, 5% of larch arabinogalactan, 5% of cyclodextrin, 5% of fruit and vegetable enzyme powder and 5% of soybean titanium powder.
The preparation method of the probiotic capsule comprises the following steps:
(1) preparing probiotic fermentation bacteria powder: centrifuging seven probiotic fermentation liquids at low temperature of 400rpm and 6 ℃, respectively, removing supernatant, collecting thalli, freeze-drying, adding glycerol (freeze-drying protective agent) with the weight of 2% of the thalli, and drying at-10 ℃ for 15 h. Drying to obtain zymophyte powder, and storing at 4 deg.C for use.
Wherein the indexes of the seven probiotics before centrifugation are as follows:
TABLE 3 probiotic indices before centrifugation
(2) Mixing the probiotic fermentation bacteria powder with the prebiotics powder: mixing and stirring the five probiotic powder and the prebiotics according to the weight percentage, wherein the stirring speed is 50rpm, carrying out secondary drying at 28 ℃ for 60min until the water content is 0.02%, and then crushing until the particle fineness is less than or equal to 100 mu m to obtain the composite probiotic powder.
(3) Filling capsules to prepare finished products: filling the composite probiotic powder into the seaweed capsule shell to obtain the probiotic capsule product.
(4) And detecting the viable count by using a flat plate counting method, wherein the viable count of the composite capsule is 760 hundred million CFU/capsule, the type of the capsule is No. 1, and the filling amount of each capsule is 0.3g and is marked as A1.
The probiotic capsule is administered orally, one granule per day. The product can be stored at room temperature.
Examples of the experiments
The product is clinically characterized and tested by the following method:
1. the main indexes of the preparation are bacterial vaginitis symptoms before and after the experiment, such as vaginal secretion and smell, Nugent score value, vaginitis remission rate and the like.
2. Basic data of volunteers: 80 women all have asymptomatic bacterial vaginitis, the average age is 24-36 years, and the taking period is 14 days. Evaluation and observation are carried out on 80 volunteers by adopting a random double-blind control method. The age of the four groups, i.e. intervention 1 group (30.2 ± 5.7), was 20 people in total. Intervention 2 groups were aged (29.6 ± 7.2) for a total of 20 people. Intervention 3 groups were aged (30.9 ± 7.2) for a total of 20 people. The age of the control group was (31.6. + -. 6.7), for a total of 20 persons. Age formation ratio differences between the four groups were not statistically significant (P > 0.05). After 14 days of intervention, vaginal secretions of the volunteers were collected separately, gram stained, and subjected to 100-fold oil microscopic examination.
3. The experimental intervention group was administered capsules A1, A2, A3, and the control group was administered placebo capsules containing ordinary starch in the same shape. The dose was taken 1 capsule per person per day in the experimental group and 1 placebo per person per day in the control group.
4. The randomized double-blind placebo parallel control method was carried out by a third party (finance department of companies) who did not participate in the evaluation, 60 volunteers were randomly numbered, and capsules a1, a2, A3 and placebo were bottled in nondifferential shapes (containing 15 capsules), randomly numbered in concealed locations of the bottle bodies, and individually sealed and stored in blind bottoms. After the evaluation to be tested is finished, the experimenter (the department of testing I) carries out data correspondence and statistical processing.
5. The Nugent score is obtained by taking 30 visual fields of a vagina secretion specimen of a volunteer stained by the gram under an oil microscope to observe and count lactobacillus, gram-stained adventitious small bacillus (Gardnerella vaginalis), gram-negative small bacillus (Bacteroides), and gram-stained adventitious campylobacter (Campylobacter mobilis), integrating values, summing and calculating the Nugent score, wherein the score is normal when the score is 0-3, and the score is transition state when the score is 4-6; BV, i.e. bacterial vaginal disease, is classified as BV at not less than 7. Wherein, the Nugent scoring system is as follows:
TABLE 4 Nugent Scoring System
Results of the test volunteer integration:
TABLE 5 subject nugent integration results
According to evaluation results, the matched probiotic formula can effectively root the vaginal environment and balance vaginal flora, so that female vaginitis symptoms are relieved.
Claims (10)
1. An oral probiotic capsule for regulating the balance of vaginal flora of women, which is characterized in that: the feed comprises 60-80% of composite probiotics, 20-40% of prebiotics and 0-20% of pharmacological auxiliary materials in percentage by mass; the composite probiotics at least comprise bacillus coagulans XP, and also comprise any one or more of lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus crispatus, lactobacillus malus and leuconostoc cremoris; the prebiotics are one or more of xylo-oligosaccharide, larch arabinogalactan, soybean titanium powder, cyclodextrin and fruit and vegetable enzyme powder; each capsule contains 200-800 hundred million CFU of composite probiotics.
2. The oral probiotic capsule for regulating the balance of vaginal flora in women according to claim 1, wherein the bacillus coagulans XP is a strain screened by the applicant and has been deposited in the China center for type culture Collection in 12 and 25 months in 2017 under the preservation registration number of CCTCC NO: M2017836. The bacillus coagulans XP (bacillus coagulans XP) belongs to the bacillus in the strain classification, is a gram-positive bacterium, and has bacterial colonies which exist singly or in pairs and rarely form a straight-chain arrangement; the cells are rod-shaped, have terminal spores and no flagellum and form endospores; the size of the single thallus is 4-6 μm in length and 0.4-0.9 μm in width.
3. The oral probiotic capsule for regulating female vaginal flora balance according to claim 1, wherein the pharmacological excipients are one or more of angelica, medlar, peach gum and atractylodes.
4. The oral probiotic capsule for regulating the balance of vaginal flora in women according to claim 1, further comprising a capsule shell made of a high molecular polymer material with slow release properties.
5. The oral probiotic capsule for regulating the balance of female vaginal flora according to claim 4, characterized in that the capsule shell is made of any one of gelatin, hydroxypropyl methylcellulose capsule, starch capsule and seaweed capsule.
6. The preparation method of the oral probiotic capsule for regulating the balance of vaginal flora of women is characterized by being completed in a GMP workshop and comprising the following steps of:
(1) preparing probiotic fermentation bacteria powder: centrifuging various probiotic fermentation liquid which form the composite probiotics at the speed of 100-500 rpm and the temperature of 4-10 ℃, separating solid from liquid, removing supernatant, collecting solid substances of the probiotics, freeze-drying the solid substances for 2-16 hours at the temperature of-15-0 ℃, and storing freeze-dried probiotic fermentation powder at the temperature of 0-10 ℃ for later use;
(2) mixing the ingredients: mixing various probiotic fermentation bacteria powder, prebiotics powder and medicinal auxiliary material powder which form the composite probiotic in proportion, and fully mixing and stirring at room temperature under the condition that the environmental humidity is 5-15%;
(3) drying, crushing and filling: and drying the mixed solid powder material at 18-40 ℃, crushing until the granularity is not more than 100 mu m to obtain the composite probiotic powder, filling the composite probiotic powder into a capsule shell, and storing at a cool place at room temperature.
7. The method for preparing an oral probiotic capsule for regulating balance of vaginal flora of women according to claim 6, wherein in the step (1) of freeze-drying, a freeze-drying protective agent is further added into the probiotic solid substance, and the addition amount of the freeze-drying protective agent is 0.5-2% of the weight of the probiotic solid substance.
8. The method for preparing oral probiotic capsule for regulating the balance of vaginal flora in women according to claim 7, wherein the lyoprotectant is one or more of glycerol, skim milk, VC and the like.
9. The method for preparing the oral probiotic capsule for regulating the balance of vaginal flora of women according to claim 5, wherein the density of the probiotic fermentation liquor selected in the step (1) is 2-20 g/L, and the content of active probiotics is 100-300 hundred million CFU/L.
10. The method for preparing oral probiotic capsules for regulating balance of vaginal flora of women according to claim 5, wherein in the drying process of the step (3), the mixing and stirring speed is 50-200 rpm, and the duration is 10-60 minutes until the water content of the powder is less than 0.05%.
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