CN108464965B

CN108464965B - Propolis mouthwash containing natural active ingredients and preparation method thereof

Info

Publication number: CN108464965B
Application number: CN201810622498.3A
Authority: CN
Inventors: 刘东春; 朱秋楠; 王芳; 苏昕; 于青; 龙美澄; 张心玥; 张雪雁; 林珠玉; 沙超
Original assignee: Shenyang Pharmaceutical University
Current assignee: Guangdong Yuanchen Pharmaceutical Technology Co.,Ltd.; Shenyang Pharmaceutical University
Priority date: 2018-06-15
Filing date: 2018-06-15
Publication date: 2021-07-23
Anticipated expiration: 2038-06-15
Also published as: CN108464965A

Abstract

The invention provides propolis mouthwash containing natural active ingredients and a preparation method thereof. The invention is prepared from the following raw materials in percentage by weight: the invention consists of the following raw materials: 0.05-2% of propolis extract, 0.1-5% of natural active ingredients, 0.05-2% of menthol, 0.5-5% of edible alcohol, 5-15% of humectant, 0.5-4% of surfactant, 0.1-2% of pH regulator, 0.01-2% of sweetening agent, 0.05-0.5% of preservative, 0.01-0.1% of pigment, 0.001-0.2% of essence and the balance of water. The preparation method comprises the following steps: (1) weighing the components according to the mass; (2) dissolving the water soluble components in water, and dissolving the other components in ethanol; (3) mixing the ethanol solution and the water solution; (4) aging; (5) filtering; (6) and (5) sterilizing and filling. The mouthwash provided by the invention can clean teeth, improve bad breath, has a remarkable antibacterial effect, and is beneficial to treatment and prevention of dental ulcer.

Description

Propolis mouthwash containing natural active ingredients and preparation method thereof

Technical Field

The invention relates to the technical field of medicines, in particular to propolis mouthwash containing natural active ingredients and a preparation method thereof. The mouthwash has pleasant smell and high safety, can clean teeth and improve oral peculiar smell, has remarkable antibacterial effect, and is beneficial to treatment and prevention of oral ulcer.

Background

With the continuous improvement of the quality of the national life, more and more people pay attention to the oral health of the people. The results of the national oral health survey report in 2017 show that: among respondents who had problems in their oral cavity, halitosis (65.8%), hemorrhage (65.8%), and ulcer (53.0%) were the three most frequent symptoms. Secondly, swelling (41.1%), dry mouth (28.4%), and others (18.7%) also become oral problems that plague people in daily life.

These oral health problems are mostly caused by the presence of pathogenic bacteria in the oral cavity. Pathogenic bacteria adhere to the acquired membrane formed by salivary protein on the tooth surface, and the acid generated by sugar is utilized to form dental plaque and dental caries. Dental plaque is also the initiating factor of periodontal disease, and chronic infection of pathogenic bacteria causes periodontitis, gingivitis: toxins produced by bacteria can cause gingival bleeding, bacterial metabolites can cause dental calculus and halitosis, and the like. In addition, pathogenic bacteria can also infect oral mucosa, causing oral candidiasis, recurrent oral ulceration, and the like. Therefore, oral hygiene is focused on controlling pathogenic bacteria.

In order to ensure oral health, the common cleaning means are: the mouthwash is a novel oral health product, has good effects on removing oral peculiar smell, reducing oral bacteria, preventing decayed teeth, resisting inflammation and easing pain, and is often used as an auxiliary treatment medicine for oral diseases such as periodontitis, gingivitis, pericoronitis, oral mucosa diseases and the like. Compared with the traditional oral cleaning method, the oral cleaning method has the advantages of cleaning the objects which can not be cleaned by brushing teeth, reducing the damage to gum, solving the oral hygiene problem of bedridden patients, solving the problem that children are unwilling to brush teeth, replacing toothpicks, solving the oral odor of smokers, being convenient to carry and the like. The results of the national oral health survey report in 2017 show that: of the respondents who were willing to try multiple oral care products, the mouthwash would be selected as the oral care product other than toothpaste in the highest proportion, 66%. Mouthwashes are gaining increasing consumer attention.

Based on the disease characteristics of related oral diseases such as decayed teeth, halitosis, dental calculus, periodontal disease, oral ulcer and the like, the propolis mouthwash provided by the invention combines the characteristics of common clinical treatment medicines and the formulation of mouthwash, and contains natural active ingredients.

Wherein, the natural active ingredients have abundant pharmacological activities, such as: silibinin has antibacterial, anti-tumor, free radical scavenging, liver protecting effects, etc. the invention mainly uses its significant antibacterial effect. Meanwhile, the plant-derived antibacterial substances are not easy to cause drug resistance (Wu Chun Wang, Lin Xiao Feng, Wang Wei, and the like, the research progress of plant-derived active ingredients [ J ]. Huai Yin institute of Industrial science, 2004,13(3):28-35), and can be used for a long time.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention aims to provide propolis mouthwash containing natural active ingredients and a preparation method thereof. The mouthwash has the advantages of high safety, effective cleaning of teeth, improvement of oral odor, alleviation of pain, remarkable antibacterial effect, contribution to treatment and prevention of oral ulcer and the like. It is characterized in that: the ethanol content is low, the oral cavity irritation is small, and the oral liquid is suitable for the old, children, drivers and other people; secondly, prevention of most oral diseases is realized from two ways: a first passage: the propolis can directly kill pathogenic bacteria and fungi in oral cavity by the action of propolis and natural active ingredients, and simultaneously, the natural active ingredients are used to effectively reduce drug resistance formed by abuse of antibiotics. And a second passage: the pH value is adjusted to 3.0-3.2, and the salivary protein forming an acquired membrane is settled, so that the formation of dental plaque is inhibited from the root, and the periodontal disease is prevented and relieved.

The invention adopts the following technical scheme to realize the purpose:

the invention relates to propolis mouthwash containing natural active ingredients, which consists of the following raw materials in percentage by weight: 0.05-2% of propolis extract, 0.1-5% of natural active ingredients, 0.05-2% of menthol, 0.5-5% of edible alcohol, 5-15% of humectant, 0.5-4% of surfactant, 0.1-2% of pH regulator, 0.01-2% of sweetening agent, 0.05-0.5% of preservative, 0.01-0.1% of pigment, 0.001-0.2% of essence and the balance of water.

Wherein, the preferable proportion of the propolis extract is 0.05-0.5%, the preferable proportion of the natural active ingredients is 0.1-0.5%, the preferable proportion of the edible alcohol is 1-2%, the preferable proportion of the pH regulator is 0.5-1.2%, and the preferable proportion of the sweetener is 0.2-1%.

The propolis extract can be obtained by the following method: freezing and storing the bee collagen at the temperature of between 25 ℃ below zero and 15 ℃ below zero for 40 to 50 hours, crushing and sieving. Soaking in 60-90% edible ethanol for 24-48 h, and then carrying out water bath at 40-60 ℃ for 3-6 h. And rapidly decompressing and recovering the solvent to dryness by using a rotary evaporator, collecting solid residues obtained after the solvent is evaporated to dryness, uniformly spreading the solid residues in a square porcelain plate, and continuously drying the solid residues in a decompression dryer for 24-48 hours to completely volatilize the solvent.

The natural active ingredient is an ingredient with antibacterial activity or an extract of a plant. Preferably, the natural active ingredients include but are not limited to one or more of baicalin, luteolin, silibinin, silymarin, breviscapine, dihydroquercetin, quercetin, myricetin, tea extract, clove extract and honeysuckle extract; preferably silybin, silymarin, tea extract, luteolin, and dihydromyricetin.

The invention carries out antibacterial tests on the propolis mouthwash prepared by different active ingredients, and the results show that the antibacterial effect is the best when the active ingredients are silybin, silymarin, tea extract, luteolin and dihydromyricetin.

The concentration of the edible alcohol is 60-95%.

The humectant is as follows: one or more of glycerol and sorbitol;

the surfactant is one or more of PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil and sodium lauroyl sarcosinate;

the sweetener is one or more of sorbitol, saccharin sodium, xylitol, stevioside, fructose and maltose;

the preservative is one or more of methylparaben and ethylparaben;

the pH regulator is malic acid, tartaric acid, citric acid, and sodium citrate;

preferably, the weight ratio of the propolis to the natural active ingredients is as follows: 0.02-5.

The surfactant is preferably PEG-60 hydrogenated castor oil.

The pH value of the propolis mouthwash is 3.0-3.2.

The invention relates to propolis mouthwash containing natural active ingredients, and the preparation method comprises the following steps:

(1) weighing the components according to the mass;

(2) dissolving the water-soluble components of humectant, pH regulator, sweetener, natural edible pigment and edible essence weighed in the step (1) in water, and dissolving the other components in ethanol;

(3) uniformly mixing the ethanol solution obtained in the step (2) with the water solution;

(4) aging the mixed solution obtained in the step (3);

(5) filtering;

(6) and (5) sterilizing and filling.

Wherein, the sterilization method in the step (6) should meet the requirement of not affecting the quality of the invention, such as ultrasonic sterilization, pasteurization, filtration sterilization and the like, so as not to destroy the quality and taste and smell.

The invention has the beneficial effects that: the propolis extract is added on the basis of ensuring that the mouthwash cleans teeth and freshes breath, so that the oral ulcer is effectively prevented and relieved; because the natural active ingredients are added, on one hand, the antibacterial property is obviously improved, and on the other hand, compared with the traditional chemical substance antibacterial mouth wash, the antibacterial mouth wash has higher safety; meanwhile, the edible ethanol content is controlled, so that the taste is mild, the smell is pleasant, and the acceptability of a user is effectively improved.

In order to better understand the essence of the present invention, the following experiments were conducted to evaluate the present invention.

(1) Clarity of the product

The clarity test was performed with reference to the clarity test method in QBT _2945 + 2012_ oral cleaning care standard. At room temperature and under natural light conditions, 25ml of the sample was poured into a 50ml stoppered cuvette and visually observed at a distance of 30 cm. The solution was observed to be clear, free of mechanical impurities. And the clarity is qualified through detection.

(2) Stability of

The stability test was performed with reference to the stability test method in QBT _2945-2012_ oral cleaning Care Standard.

Thermal stability: pouring 25ml of sample into a colorimetric tube with a plug (50ml), placing the colorimetric tube in a constant temperature incubator (with precision +/-1 ℃) at the temperature of 40 +/-1 ℃) for 24 hours, taking out the colorimetric tube, returning to the room temperature, and carrying out visual observation under natural light. The result is no agglomeration or turbidity, and the heat resistance stability is qualified.

② cold resistance and stability: pouring 25ml of sample into a colorimetric tube with a plug (50ml), placing the colorimetric tube in a refrigerator (with precision +/-1 ℃) at the temperature of 0-4 ℃ for 24 hours, taking out the colorimetric tube, returning the colorimetric tube to the room temperature, and carrying out visual observation under natural light. The result is not frozen, the color is stable, and the cold resistance stability is qualified.

(3) Evaluation on trial

Randomly recruiting 12 volunteers for trial training, and performing double-blind trial evaluation on the mouthwash product and a certain commercially available propolis mouthwash, wherein the evaluation items and standards are shown in table 1.

TABLE 1 mouthwash usage scoring criteria

After double-blind tests, the results are counted, and the final score of the mouthwash product is the ratio of the mouthwash water of the invention to the mouthwash water of a certain commercially available propolis. The statistical results are shown in Table 2, and the average scores of all the ingredients are more than 1, which indicates that the mouthwash of the present invention is comfortable for most users.

TABLE 2 evaluation statistics on mouthwash trials

(4) Ethanol content determination

Detecting the content of ethanol in the product by adopting a gas chromatography, wherein the gas chromatography conditions are as follows: using a capillary chromatography column, FID detector; column temperature: 65 ℃; detector temperature: 200 ℃; a sample inlet is 200 ℃; nitrogen flow rate 30 ml/min; the hydrogen flow rate is 40 ml/min; air flow rate is 400 ml/min; the split ratio is 10: 1; temperature rising procedure: keeping the temperature at 65 ℃ for 2min, heating to 120 ℃ at 6 ℃/min, and keeping the temperature for 3 min. The amount of sample was 1. mu.l. The gas chromatogram results are shown in FIG. 1, with peak 1 being the ethanol peak. The ethanol content is calculated to be within the range of 0.5 to 5 percent.

(5) In vitro antibacterial experiments

The in vitro antibacterial experiment is carried out by adopting a tube-disc method of an antibacterial ring method. The negative control was physiological saline.

Taking 3 sets of sterile culture dishes, adding about 20ml of beef extract peptone agar culture medium respectively, and placing on a horizontal glass plate for solidification to serve as a bottom layer. And taking another 50ml beef extract peptone agar culture medium cooled to about 50 ℃, adding 1ml escherichia coli suspension, quickly shaking uniformly, pouring the mixed culture medium on a bottom layer flat plate to serve as a bacterium layer, and placing the flat plate on a horizontal glass plate for solidification to obtain the mixed bacterium double-layer flat plate.

The bottom of the culture medium plate is marked with the corresponding strain and sample number, and 1 sterilized Oxford cup is placed in each culture dish at equal distance by using an elbow forceps. Mu.l of the control and sample solutions were added to the Oxford cup with a pipette and the lid replaced. And (4) stably sending the culture dish into a constant temperature box, and incubating for 16-18 h at 37 ℃. And measuring the diameter of the inhibition zone by using a vernier caliper.

The operation of the staphylococcus aureus and the candida albicans is the same as that of the staphylococcus aureus, the incubation time of the staphylococcus aureus is 16-18 hours, the candida albicans culture medium is a Sabouraud's culture medium, and the incubation time is 36-48 hours.

The experimental results are shown in table 3, and the product of the invention has significant antibacterial activity on staphylococcus aureus, escherichia coli and candida albicans.

TABLE 3 statistical results of zone of inhibition in vitro antibacterial experiments

In the invention, the propolis extract and natural active ingredients are added into the mouthwash, wherein the propolis has the functions of resisting bacteria, viruses, protozoa, oxidation, blood fat and the like. Natural active ingredients have rich pharmacological activities, such as: silibinin has antibacterial, anti-tumor, free radical scavenging, liver protecting effects, etc. the invention mainly uses its significant antibacterial effect. Meanwhile, the plant-derived antibacterial substance is not easy to cause drug resistance and can be used for a long time.

Drawings

FIG. 1 is a gas chromatogram for ethanol content. Wherein peak 1 is the ethanol peak.

Detailed Description

Example 1

0.1006g of propolis extract, 1.02g of tea extract, 0.0802g of menthol, 3.53g of edible alcohol, 5.08g of glycerol, 0.60g of PEG-40 hydrogenated castor oil, 2.54g of PEG-60 hydrogenated castor oil, 0.50g of citric acid, 1.25g of xylitol, 0.05g of methyl paraben, 0.02g of caramel pigment, 0.0053g of mint essence and water are respectively weighed and added to 100g of water. Respectively and completely dissolving in water and ethanol according to the solubility, mixing, standing and aging for 24h, filtering, ultrasonic sterilizing, and packaging.

Example 2

Weighing propolis extract 0.1500g, silymarin 0.0055g, menthol 0.0714g, edible alcohol 4.03g, glycerol 10.00g, PEG-60 hydrogenated castor oil 0.60g, citric acid 1.40g, sodium citrate 0.11g, xylitol 1.25g, methyl hydroxybenzoate 0.05g, beet red pigment 0.03g, white lemon essence 0.0072g, and adding water to 100 g. Respectively and completely dissolving in water and ethanol according to the solubility, mixing, standing and aging for 24h, filtering, ultrasonic sterilizing, and packaging.

Example 3

Weighing propolis extract 0.1512g, luteolin 0.0062g, menthol 0.0712g, edible alcohol 1.56g, glycerol 10.24g, PEG-60 hydrogenated castor oil 0.40g, citric acid 1.50g, saccharin sodium 0.03g, methyl hydroxybenzoate 0.06g, caramel pigment 0.08g, apple essence 0.0078g, and adding water to 100 g. Respectively and completely dissolving in water and ethanol according to the solubility, mixing, standing and aging for 24h, filtering, ultrasonic sterilizing, and packaging.

Example 4

Respectively weighing propolis extract 0.1200g, silibinin 0.3100g, menthol 0.0800g, edible alcohol 3.52g, glycerol 15.08g, PEG-60 hydrogenated castor oil 0.82g, citric acid 0.81g, sodium citrate 0.08g, malic acid 0.11g, xylitol 1.25g, methyl hydroxybenzoate 0.06g, beet red pigment 0.02g, spearmint essence 0.0077g, and adding water to 100 g. Respectively and completely dissolving in water and ethanol according to the solubility, mixing, standing and aging for 24h, filtering, ultrasonic sterilizing, and packaging.

Example 5

0.0810g of propolis extract, 0.2901g of dihydromyricetin, 0.0610g of menthol, 2.64g of edible alcohol, 8.08g of glycerol, 0.88g of PEG-40 hydrogenated castor oil, 0.62g of citric acid, 0.18g of sodium citrate, 0.32g of xylitol, 0.03g of saccharin sodium, 0.05g of methyl paraben, 0.05g of caramel pigment, 0.0053g of orange essence and 100g of water are respectively weighed. Respectively and completely dissolving in water and ethanol according to the solubility, mixing, standing and aging for 24h, filtering, ultrasonic sterilizing, and packaging.

Claims

1. Propolis mouthwash containing natural active ingredients is characterized in that: 0.05-0.5% of propolis extract, 0.1-0.5% of natural active ingredients, 0.05-2% of menthol, 0.5-5% of edible alcohol, 5-15% of humectant, 0.5-4% of surfactant, 0.5-1.2% of pH regulator, 0.01-2% of sweetening agent, 0.01-0.05% of edible preservative, 0.01-0.1% of natural edible pigment, 0.001-0.2% of edible essence and the balance of water, wherein the natural active ingredients are silybin or dihydromyricetin, and the weight ratio of the propolis extract to the natural active ingredients is as follows: 0.02-5.

2. The propolis mouthwash containing natural active ingredients of claim 1, characterized by: the edible alcohol is 1% -2%, the pH regulator is 0.5% -1.2%, the sweetening agent is 0.2% -1%, and the concentration of the edible alcohol is 60% -95%.

3. The propolis mouthwash containing natural active ingredients according to claim 1 or 2, characterized in that: the propolis extract is prepared by the following method: freezing and storing the bee collagen for 40-50 h at the temperature of-25 to-15 ℃, crushing, sieving, soaking in 60-90% edible ethanol for 24-48 h, carrying out water bath for 3-6 h at the temperature of 40-60 ℃, rapidly reducing pressure and recovering to dryness by using a rotary evaporator, collecting solid residues after solvent evaporation, uniformly spreading in a square ceramic disc, and continuously drying in a reduced-pressure drier for 24-48 h to completely volatilize the solvent.

4. The propolis mouthwash containing natural active ingredients of claim 1, characterized in that: the concentration of the edible alcohol is 60% -95%.

5. The propolis mouthwash containing natural active ingredients of claim 1, characterized in that: the humectant is one or more of glycerol and sorbitol; the surfactant is one or more of PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil and sodium lauroyl sarcosinate; the pH regulator is one or more of malic acid, tartaric acid, citric acid and sodium citrate; the sweetener is one or more of sorbitol, saccharin sodium, xylitol, stevioside, fructose and maltose: the edible preservative is one or more of methyl paraben and ethyl paraben; the natural edible pigment is one or more of caramel pigment and beet red pigment; the edible essence is one or more of lemon essence, sweet orange essence, apple essence, blueberry essence, spearmint essence and mint essence.

6. The method for preparing propolis mouthwash containing natural active ingredients according to claim 1, characterized in that: the method comprises the following steps:

(1) weighing the components according to the mass;

(2) dissolving the water-soluble components weighed in the step (1), namely the humectant, the pH regulator, the sweetener, the natural edible pigment and the edible essence in water, and dissolving the other components in ethanol;

(4) aging the mixed solution obtained in the step (3);

(5) filtering;

(6) and (5) sterilizing and filling.

7. The method for preparing propolis mouthwash containing natural active ingredients according to claim 6, characterized in that: the above-mentioned

And (4) aging for 12-24 h, wherein the sterilization method in the step (6) comprises but is not limited to ultrasonic sterilization, pasteurization and filter sterilization, and preferably ultrasonic sterilization.

8. Propolis mouthwash containing natural active ingredients is characterized in that: respectively weighing propolis extract 0.1200g, silibinin 0.3100g, menthol 0.0800g, edible alcohol 3.52g, glycerin 15.08g, PEG-60 hydrogenated castor oil 0.82g, citric acid 0.81g, sodium citrate 0.08g, malic acid 0.11g, xylitol 1.25g, methyl hydroxybenzoate 0.06g, beet red pigment 0.02g, spearmint essence 0.0077g, adding water to 100g, respectively and completely dissolving in water and ethanol according to the solubility, mixing uniformly, standing and aging for 24h, filtering, sterilizing with ultrasound, and packaging.

9. Propolis mouthwash containing natural active ingredients is characterized in that: 0.0810g of propolis extract, 0.2901g of dihydromyricetin, 0.0610g of menthol, 2.64g of edible alcohol, 8.08g of glycerol, 0.88g of PEG-40 hydrogenated castor oil, 0.62g of citric acid, 0.18g of sodium citrate, 0.32g of xylitol, 0.03g of saccharin sodium, 0.05g of methyl paraben, 0.05g of caramel pigment and 0.0053g of sweet orange essence are respectively weighed and added with water to 100g, and the components are respectively and completely dissolved in water and ethanol according to the dissolubility, uniformly mixed, kept stand and aged for 24h, filtered, sterilized by ultrasound and filled.