WO2016011978A1 - Composition with multiple oral treatment and healthcare functions and preparation method therefor - Google Patents

Abstract

A composition with multiple oral treatment and healthcare functions. The composition comprises: quasi-nanoscale bioactive mineral powder, a protective agent, an adhesive, a moisturizer and other ingredients. Also disclosed are a preparation method for the composition and an application of the composition in the preparation of medicines or dental products for preventing hemodia, periodontal diseases, dental ulcer and plaque-induced dental caries.

Description

Composition with multiple oral treatment and health care effect and preparation method thereof Technical field

The present invention relates to the field of oral treatment and health care, and in particular to a composition having multiple oral treatment and health effects and a preparation method thereof, and to the use of the composition in oral treatment and health care.

Background technique

Dental allergy is a common and frequently-occurring disease in the oral cavity. The global incidence rate is about 40%, the domestic incidence rate is also 30%, and the incidence rate in periodontal disease patients is as high as 98%. The causes of dental allergies are various, such as wedge-shaped defects, periodontal atrophy root exposure, external tooth injury, severe wear and other dentin exposure, or iatrogenic tooth preparation, cavity preparation, tooth cleaning, scraping Treatment, dentin exposure caused by tooth discoloration. However, the basic pathogenesis has formed a unified theory in the industry - "liquid dynamics theory", that tooth hypersensitivity is due to the exposure of dentinal tubules, causing internal dentin fluid to flow inside and outside after stimulation, causing dentin cells and their processes. The expansion and compression, which mechanically agitates the end of the pulp nerve and causes pain. At present, the mechanism for treating dentin hypersensitivity is to change the permeability of dentinal tubules and to reduce the excitability of the pulpal nerves. Clinically, there are four aspects to the mechanism of drug desensitization: 1 Blocking: A drug that produces insoluble precipitates is applied to the tooth surface to produce a precipitate to block the dentinal tubules. 2 Corrosion: Corrosive drugs are used to coagulate and denature proteins in dentin, reducing the permeability of small tubes. 3 covering effect: the resin material is used to form a protective film on the surface of the dentin to isolate the stimulation; 4 biological action: a drug that can activate the vitality of the dentin cells to form a repairing dentin, so that the dentin is calcified and the stimulation is isolated.

Periodontal disease refers to a chronic destructive and progressive disease of the tooth supporting tissues, that is, the gums, periodontal ligament and alveolar bone, and is one of the common diseases in the oral cavity. Periodontitis is common in the population, especially chronic periodontitis, and its prevalence increases after age 35. At present, the prevalence of periodontitis in the Chinese population is 70-85%, and the prevalence rate gradually increases with age. Periodontitis has been Medical definition is the "number one killer" of oral health. The progression of periodontal disease can make the gums inflamed, periodontal membrane degeneration, alveolar bone absorption, and finally loosening and falling off the teeth, causing chewing function and digestive dysfunction and obstacles, which have a great impact on human health. Periodontal disease is a multifactorial disease, and its initiating factor is the accumulation of bacteria and its products in dental plaque, thus inhibiting the growth of oral pathogenic bacteria can effectively alleviate periodontal disease.

Bioactive glass was discovered in 1969 by Professor Hench LL. of the United States, and systematically studied the relationship between the Na ₂ O-CaO-SiO ₂ system glass and its biocompatibility. Bioactive glass has both osteogenic and osteoconductive effects, and has good binding to both bone and soft tissues. It is considered to be a good biomaterial that can be applied in the field of repair. Since then, the Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ system bioactive glass has been developed, which forms apatite crystallites in a Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ glass matrix. After being implanted into the human body, a hydroxyl group is obtained from the human body fluid and a surface hydroxyapatite layer is formed, thereby exhibiting surface biological activity. Bioactive glass can react rapidly and continuously with water and saliva, release calcium ions and phosphate ions, replenish dental minerals and deposit on dentinal tubules. Long-term action can produce stable crystalline hydroxyapatite layer and reduce Dentin hypersensitivity reaction.

Quasi-nano-scale bioactive mineral powder is an improvement of bioactive glass. Through precision processing technology, quasi-nano-scale bioactive mineral powder is produced, which greatly increases the specific surface area and improves the reactivity. The bioactive glass particles currently used for dentistry have a particle size of the order of micrometers, while the dentinal tubules are in the shape of an inverted cone-shaped tube having a diameter of about 3 to 4 μm near the end of the pulp and about 1 μm at the near surface. The active glass powder can not enter the inside of the dentinal tubule. The mechanism of the formation of hydroxyapatite by relying on the deposition of calcium and phosphorus ions only has a limited and slow contribution to the closed dentinal tubule. At the same time, it depends on the hydroxyphosphorus formed by the mineralized phase. Graystone is not stable, which leads to excessive treatment of dentin hypersensitivity, and dentinal tubules are sometimes not completely blocked. The quasi-nano-scale bioactive mineral powder can directly enter the exposed dentinal tubules, and can form a stable hydroxyapatite structure to seal the dentinal tubules in the surface and inside of the dentinal tubules, block the dentinal tubules, and induce new teeth. The glaze is formed to fundamentally treat dentin hypersensitivity. Quasi-nano When the biologically active mineral powder is in contact with body fluid or water, it releases calcium ions and phosphate ions, and at the same time forms a local high pH environment, thereby inhibiting the growth of various pathogenic bacteria in the oral cavity, and killing after prolonged contact. A disease that causes periodontal disease, which relieves periodontal disease, improves the oral environment, maintains healthy teeth, and prevents dental diseases.

Chitosan and its derivatives have unique physicochemical properties and biological activities. Its bactericidal and anti-inflammatory effects can be used to treat oral diseases. In addition, it has a certain protective effect on oral mucosa tissue, which can avoid enamel, gum and soft tissue damage. Hyaluronic acid is an acid mucopolysaccharide that exhibits many important physiological functions in the body due to its unique molecular structure and physicochemical properties. Sodium hyaluronate itself is one of the components of human skin, and it is the most widely distributed acidic slime in the human body. It has a good moisturizing effect and promotes mucosal healing.

Patent document CN1528260A discloses a toothpaste composition comprising a potassium salt and a barium salt, the components of which comprise a moisturizer, a friction agent, a binder, a surfactant, a sweetener, a perfume, water and the like. After brushing the teeth for a few weeks, the sensitivity of the teeth is reduced. The mechanism of desensitization of potassium ions is mainly to increase the concentration of potassium ions around the sensory nerve receptors of the pulp, and to depolarize and reduce the excitability of the nerves, thereby reducing the dentin. Symptoms of pain caused by allergies. However, potassium ions can not occlude dentinal tubules. The use of this composition only relies on the release of potassium ions to alleviate the pain symptoms caused by dentin hypersensitivity. It cannot fundamentally treat dentin hypersensitivity. Once it is stopped, pain symptoms will appear. It belongs to "the palliative is not a cure." In addition, this composition does not inhibit bacterial growth, and does not have oral treatment and health effects such as inhibiting gingivitis, relieving periodontitis, and anti-caries.

Patent document CN1213355A discloses a bioactive glass composition. The composition contains particles having a particle size of 90 μm, which can rapidly react with body fluids to release Ca and P ions, thereby producing a hydroxycarbonate apatite layer, thereby reducing dentin hypersensitivity. However, the bioactive glass particles of the invention have a particle size of the order of micrometers, and it is difficult to form hydroxyapatite inside the dentinal tubules, so that the long-term effect is unsatisfactory and unstable.

Patent document CN102826752A discloses a bioactive mineral powder containing quasi-nanoscale particles, the active mineral powder containing the following components by weight: 40 to 65% SiO ₂ , 15 to 30% CaO, Na ₂ O 15 to 30%, P ₂ O ₅ 2 to 8%; and a particle diameter range of less than 90 μm, wherein the quasi-nano-sized particles having a pore diameter in the range of 100 to 900 nm are 0.1 to 20.0% by weight. The bioactive mineral powder provided by the literature has a particle size of less than 90 μm and contains quasi-nano-sized particles which can directly enter the dentinal tubule and directly seal it, thereby shortening the treatment time and increasing the sealing rate, and improving the sensitivity to dentin. treatment effect. However, this document does not address the rational formulation and related preparation methods for preparing quasi-nanoscale active mineral powders into oral therapeutic and health care products.

Patent document CN1739483A discloses an antibacterial toothpaste. The composition component comprises a bactericide, a humectant, a friction agent, a binder, a surfactant, a sweetener, a fragrance, water, and the like. The bactericide is carboxymethyl chitosan, which can inhibit the pathogenic bacteria in the oral cavity. However, the invention can only inhibit the growth of bacteria in the oral cavity, and has no effect on oral diseases such as dentin hypersensitivity, periodontal disease, and oral ulcer.

Summary of the invention

It is an object of the present invention to provide a composition having multiple oral treatments and health benefits and a method of preparing the composition.

The present invention provides a composition having multiple oral treatments and health benefits comprising the following components: quasi-nanoscale bioactive mineral powders, protectants, binders, humectants and other ingredients.

Specifically, it comprises the following components by weight: quasi-nano-scale bioactive mineral powder, quasi-nano-scale bioactive mineral powder 2 to 50 parts, protective agent 0.1 to 5 parts, binder 0.1 to 5 parts, moisturizing 40 to 80 parts of the agent and 0.1 to 40 parts of other ingredients.

Preferably, it comprises the following components by weight: 5 to 30 parts of the quasi-nano-scale bioactive mineral powder, 0.2 to 4.5 parts of the protective agent, 0.2 to 3.5 parts of the binder, 50 to 80 parts of the humectant, and other ingredients 8 ~34 copies.

Further preferably, it comprises the following components by weight: 5 to 20 parts of the quasi-nano-scale bioactive mineral powder, 3 to 4.5 parts of the protective agent, 0.5 to 3.5 parts of the binder, 55 to 75 parts of the humectant, and other ingredients 10 ~34 copies.

Still more preferably, it comprises the following components by weight: 7.5 to 15 parts of the quasi-nano-scale bioactive mineral powder, 3.5 to 4.5 parts of the protective agent, 0.6 to 3.5 parts of the binder, 65 to 73 parts of the humectant, and other ingredients. 10 to 16 servings.

In the above composition:

The parts by weight may be a weight unit known in the medical field such as μm, mg, g, kg, or the like, and may be a multiple thereof such as 1/10, 1/100, 10 times, 100 times or the like.

The quasi-nano-scale biologically active mineral powder can be prepared by the method of CN102826752A, which contains the following components by weight: SiO ₂ 45-61%, CaO 17-27%, Na ₂ O 19-25%, P ₂ O ₅ 2.6 to 6%.

The quasi-nano-scale bioactive mineral powder has a volume of less than 90 μm, wherein the quasi-nano-sized powder having a particle diameter in the range of 100 to 900 nm accounts for 5 to 20%, preferably 5 to 10%, of the total powder. .

The protective agent is selected from one or a mixture of two of a water-soluble chitosan derivative or sodium hyaluronate, preferably a mixture of a chitosan water-soluble derivative and sodium hyaluronate; the chitosan is water-soluble The derivative is preferably carboxymethyl chitosan.

The binder is selected from one or more of carbomer, sodium carboxymethylcellulose, guar gum or carrageenan, preferably one or more of carbomer or carbomer mixture.

The humectant is selected from one or more of glycerin, polyethylene glycol or sorbitol.

The other ingredients are selected from one or more of a surfactant, a thickener, a sweetener or a fragrance.

among them:

The surfactant is selected from one or more of an alkyl glycoside, sodium lauryl sulfate, sucrose ester, sodium N-lauroyl sarcosinate or sodium dodecylbenzene sulfonate.

The thickener is selected from one or both of silica or magnesium aluminum silicate.

The sweetener is selected from one or more of acesulfame, sodium saccharin, erythritol or xylitol.

The fragrance is selected from the group consisting of aromatic alcohols, aromatics or anthraquinones, and the flavors include mint, lemon, green tea or jasmine.

A specific embodiment of the composition is a cream gel or paste.

The invention also provides a preparation method of the above composition, which is a preparation method of waterless vacuum high-speed emulsification, comprising the following steps:

Under the condition of vacuum and high-speed emulsification, add protective agent, moisturizer, and binder according to the formula, stir for 5 to 60 minutes, let stand, and then obtain the mixture, and then continue under vacuum and high-speed emulsification and stirring. Formulation The quasi-nano-scale bioactive mineral powder and other ingredients are added to the above mixture, stirred for 5 to 60 minutes, and allowed to stand for 5 to 30 minutes, and the composition is obtained.

Specifically, the method includes the following steps:

1) setting the vacuum degree to -70 ~ -101kPa, high-speed emulsification and stirring, stirring speed is 500 ~ 2500 rev / min, adding a protective agent, a moisturizer, and a binder according to the formula, stirring for 5 to 60 minutes;

2) The vacuum is allowed to stand, and the standing time is 10 to 40 hours, until the mixture is in a uniform transparent solid-liquid mixed phase, that is, the mixture is obtained;

3) setting the vacuum degree to -70 to -101 kPa, high-speed emulsification and stirring, the stirring speed is 500 to 2500 rpm, and the quasi-nano-scale biologically active mineral powder and other components are added in the mixture obtained in the step 2). Stir for 5 to 60 minutes;

4) The product obtained in the step 3) is allowed to stand under vacuum and allowed to stand for 5 to 30 minutes until the mixture is in a uniform viscous paste, that is, the composition is obtained.

The steps 1) and 3) start the scraping wall stirring at the same time of high-speed emulsification and stirring, and the stirring speed of the scraping wall is 5 to 80 rpm; the scraping wall stirring and the high-speed emulsification mixing can make the powder and the auxiliary material disperse more. Evenly.

The present invention also provides the use of the above composition for the preparation of a medicament or a dental article for preventing and treating dental hypersensitivity, periodontal disease, oral ulcer and plaque rickets.

The therapeutic and health effects of the compositions provided by the present invention are specifically described as follows:

1. The composition provided by the present invention can prevent and treat dentin hypersensitivity efficiently and stably. The invention adopts quasi-nano-scale biologically active mineral powder, can produce stable hydroxyapatite to seal dentinal tubules in exposed dentinal tubules, induce new enamel surface formation, and change the permeability of dentinal tubules, Essentially eliminate the phenomenon of dentin hypersensitivity. Compared to traditional bioactive glass, quasi-nano-scale bioactive mineral powders are more effective in treating allergies to teeth. In addition, the unique physiological remineralization activity of quasi-nano-scale bioactive mineral powders can repair tooth defects and induce enamel formation.

2. The composition provided by the present invention can prevent and treat oral diseases such as periodontal disease, oral ulcer and plaque rickets. It has been proved in literatures and experiments that quasi-nano-scale bioactive mineral powders have antibacterial properties and can inhibit Actinobacter, Streptococcus, Porphyromonas gingivalis, P. intermedia, Treponema pallidum, etc. in the oral cavity. Thereby inhibiting the onset of periodontal disease, gingivitis, mouth ulcers, caries, and the like. In addition, quasi-nano-scale bioactive mineral powders have unique surface activity, which can increase local oxygen pressure and pH when in contact with soft tissues, adsorb surrounding cells, fibrin and collagen, and rapidly form calcium and phosphorus layers. To promote the healing of oral ulcers.

3. The composition provided by the present invention contains a water-soluble derivative of chitosan and sodium hyaluronate. The water-soluble derivative of chitosan and sodium hyaluronate have good biocompatibility and antibacterial activity, and can be combined with biologically active mineral powder to inhibit various pathogenic bacteria in the oral cavity. The water-soluble derivative of chitosan and sodium hyaluronate protect oral mucosa, enamel and gums, and protect various tissues in the oral cavity while treating dentin hypersensitivity, periodontal disease and oral ulcers, and maintain oral health.

The technology provided by the present invention has the following advantages:

1. The bioactive mineral powder used in the composition provided by the present invention is quasi-nanoscale. The powder has various oral treatments and health effects such as anti-dental hypersensitivity, treatment of periodontal disease, treatment of oral ulcers, anti-caries and the like.

2. The composition formula provided by the invention is designed for the quasi-nano-scale bioactive mineral powder, the composition ratio and the auxiliary material addition sequence and the vacuum high-speed emulsification matching auxiliary scraping wall The agitated agitation method allows the quasi-nanoscale bioactive mineral powder to be more uniformly dispersed in the composition.

3. The preparation method of the composition provided by the present invention is an anhydrous preparation method. The method can maintain the activity of the biologically active mineral powder for a long time, and is beneficial to the full contact of the biologically active mineral powder with the teeth, so that it plays a better role in the oral cavity.

4. The present invention provides a process for adding a chitosan water-soluble derivative and sodium hyaluronate. The chitosan water-soluble derivative and sodium hyaluronate are inherently less soluble in an organic solvent, and the composition provided by the present invention can be uniformly dispersed in the composition to more uniformly and fully function.

DRAWINGS

1 is a drum apparatus used for the pH of a test composition in Experimental Example 1, in which A1 to A5, B1 to B5, and C1 to C5 are respectively 15 sampling sites.

detailed description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

Example 1: Preparation of a composition with multiple oral treatments and health benefits

1. Weigh each material according to the following formula:

The quasi-nano-scale bioactive mineral powder contains the following components by weight: SiO ₂ 45%, CaO 24.5%, Na ₂ O 24.5%, P ₂ O ₅ 6%; wherein the particle size is in the range of 100-900 nm The quasi-nano-sized powder accounts for 7% of the total powder weight.

2. Preparation method:

1) Set the vacuum to -70 kPa, high-speed emulsification and stirring, stirring speed is 500 rpm, scraping wall stirring speed is 20 rpm, add moisturizer, protective agent, binder, spice according to the formula, stir for 60 minutes. ;

2) The vacuum is allowed to stand until the mixture is in a uniform solid-liquid mixed phase, and the standing time is 25 hours, that is, the mixture is obtained;

3) setting the vacuum degree to -70 kPa, high-speed emulsification stirring, stirring speed is 500 rpm, the wall scraping speed is 20 rpm, and the quasi-nano-scale bioactive mineral powder is added to the product obtained in step 2). Body, thickener, surfactant, sweetener, stirred for 60 minutes;

4) The product obtained in the step 3) is allowed to stand under vacuum until the mixture is in a uniform viscous paste, that is, the composition is obtained.

Example 2: Preparation of a composition with multiple oral treatments and health benefits

1. Weigh each material according to the following formula:

The quasi-nano-scale bioactive mineral powder contains the following components by weight: SiO ₂ 45%, CaO 24.5%, Na ₂ O 24.5%, P ₂ O ₅ 6%; wherein the particle size is in the range of 100-900 nm The quasi-nano-sized powder accounts for 5% of the total powder weight.

2. Preparation method:

1) Set the vacuum to -80 kPa, high speed emulsification and agitation speed of 1200 rpm / In minutes, the wall stirring speed was 30 rpm, and the humectant, protective agent, binder, and flavor were added according to the formula, and stirred for 35 minutes;

2) The vacuum is allowed to stand until the mixture is in a uniform solid-liquid mixed phase, and the standing time is 25 hours, that is, the mixture is obtained;

3) Set the vacuum degree to -80 kPa, high-speed emulsification and agitation, the stirring speed is 1200 rpm, the scraping wall stirring speed is 30 rpm, and the quasi-nano-scale bioactive mineral powder is added to the product obtained in the step 2). Body, thickener, surfactant, sweetener, stirred for 20 minutes;

4) The product obtained in the step 3) is allowed to stand under vacuum until the mixture is in a uniform viscous paste, that is, the composition is obtained.

Example 3: Preparation of a composition with multiple oral treatments and health benefits

1. Weigh each material according to the following formula:

The quasi-nano-scale bioactive mineral powder contains the following components by weight: SiO ₂ 45%, CaO 24.5%, Na ₂ O 24.5%, P ₂ O ₅ 6%; wherein the particle size is in the range of 100-900 nm The quasi-nano-sized powder accounts for 20% of the total powder weight.

2. Preparation method:

1) Set the vacuum degree to -80kPa, high-speed emulsification and agitation, the stirring speed is 1000 rev / min, the scraping wall stirring speed is 40 rev / min, add moisturizer, protective agent, binder, spice according to the formula, stir for 50 minutes. ;

2) The vacuum is allowed to stand until the mixture is in a uniform solid-liquid mixed phase, and the standing time is 10 hours, that is, the mixture is obtained;

3) Set the vacuum degree to -80 kPa, high-speed emulsification and agitation, the stirring speed is 1000 rpm, the scraping wall stirring speed is 40 rpm, and the quasi-nano-scale bioactive mineral powder is added to the product obtained in the step 2). Body, thickener, surfactant, sweetener, stir for 45 minutes;

4) The product obtained in the step 3) is allowed to stand under vacuum until the mixture is in a uniform viscous paste, that is, the composition is obtained.

Example 4: Preparation of a composition with multiple oral treatments and health benefits

1. Weigh each material according to the following formula:

The quasi-nano-scale bioactive mineral powder contains the following components by weight: SiO ₂ 45%, CaO 24.5%, Na ₂ O 24.5%, P ₂ O ₅ 6%; wherein the particle size is in the range of 100-900 nm The quasi-nano-sized powder accounts for 15% of the total powder weight.

2. Preparation method:

1) Set the vacuum degree to -90kPa, high-speed emulsification and agitation, the stirring speed is 1500 rev / min, the scraping wall stirring speed is 60 rev / min, add humectant, protective agent, binder, spice according to the formula, stir for 40 minutes. ;

2) The vacuum is allowed to stand until the mixture is in a uniform solid-liquid mixed phase, and the standing time is 30 hours, that is, the mixture is obtained;

3) Set the vacuum degree to -90 kPa, high-speed emulsification and stirring, the stirring speed is 1500 rpm, the scraping wall stirring speed is 60 rpm, and the quasi-nano-scale bioactive mineral powder is added to the product obtained in step 2). Body, thickener, surfactant, sweetener, stir for 40 minutes;

4) The product obtained in the step 3) is allowed to stand under vacuum until the mixture is in a uniform viscous paste, that is, the composition is obtained.

Example 5: Preparation of a composition with multiple oral treatments and health benefits

1. Weigh each material according to the following formula:

The quasi-nano-scale bioactive mineral powder contains the following components by weight: SiO ₂ 45%, CaO 24.5%, Na ₂ O 24.5%, P ₂ O ₅ 6%; wherein the particle size is in the range of 100-900 nm The quasi-nano-sized powder accounts for 12% of the total powder weight.

2. Preparation method:

1) Set the vacuum degree to -90kPa, high-speed emulsification and agitation, the stirring speed is 2500 rev / min, the scraping wall stirring speed is 5 rev / min, add humectant, protective agent, binder, spice according to the formula, stir for 5 minutes. ;

2) The vacuum is allowed to stand until the mixture is in a uniform solid-liquid mixed phase, and the standing time is 25 hours, that is, the mixture is obtained;

3) Set the vacuum degree to -90 kPa, high-speed emulsification and stirring, the stirring speed is 2500 rpm, the scraping wall stirring speed is 10 rpm, and the product obtained in the step 2) is added according to the formula. The nano-scale biologically active mineral powder, thickener, surfactant, sweetener are incorporated, and stirred for 10 minutes;

4) The product obtained in the step 3) is allowed to stand under vacuum until the mixture is in a uniform viscous paste, that is, the composition is obtained.

Example 6: Preparation of a composition with multiple oral treatments and health benefits

1. Weigh each material according to the following formula:

The quasi-nano-scale bioactive mineral powder contains the following components by weight: SiO ₂ 45%, CaO 24.5%, Na ₂ O 24.5%, P ₂ O ₅ 6%; wherein the particle size is in the range of 100-900 nm The quasi-nano-sized powder accounts for 15% of the total powder weight.

2. Preparation method:

1) Set the vacuum degree to -101 kPa, high-speed emulsification and agitation, the stirring speed is 2000 rpm, the scraping wall stirring speed is 80 rpm, and the humectant, protective agent, binder, and fragrance are added according to the formula, and the mixture is stirred for 10 minutes. ;

2) The vacuum is allowed to stand until the mixture is in a uniform solid-liquid mixed phase, and the standing time is 40 hours, that is, the mixture is obtained;

3) Set the vacuum degree to -101 kPa, high-speed emulsification and stirring, the stirring speed is 2500 rpm, the scraping wall stirring speed is 80 rpm, and the quasi-nano-scale bioactive mineral powder is added to the product obtained in step 2). Body, thickener, surfactant, sweetener, stir for 15 minutes;

4) The product obtained in the step 3) is allowed to stand under vacuum until the mixture is in a uniform viscous paste, that is, the composition is obtained.

Comparative example 1:

1. Weigh each material according to the following formula:

2. Preparation method: same as in Example 2.

Comparative example 2:

1. Weigh each material according to the following formula:

2. Preparation method: same as in Example 3.

Comparative example 3:

1. Weigh each material according to the following formula:

2. Preparation method: same as in Example 2.

3. According to the ratio of the materials in the comparative example 3, the preparation method is the same as that in the second embodiment. After the paste is left to stand for several hours, there will be visible delamination, that is, the powder and the humectant are separated, the powder is at the bottom layer, and the moisturizer is located. Upper layer, cannot be filled and cannot be used.

Comparative example 4:

1. Weigh each material according to the following formula:

2. Preparation method: same as in Example 3.

3. According to the ratio of the materials in the comparative example 4, the preparation method is the same as that in the third embodiment, and the paste formed has agglomeration phenomenon, that is, the powder and the thickener are not uniformly dispersed in the colloid, and the bioactive mineral powder in the paste is obtained. The body does not work continuously and stably, and the paste has a rough appearance and is thick and difficult to fill.

Experimental Example 1: Detection of quasi-nanoscale bioactive powder distribution uniformity

Since the bioactive powder in the present invention is quasi-nanoscale, it is not easy to be uniform according to a conventional method. Dispersed in the composition. The quasi-nano-scale bioactive powder has strong alkalinity, and if the dispersion is uneven, the pH difference of different parts of the composition is large. Therefore, the combination prepared by the method of the present invention can be judged by detecting the pH value of the composition of different take-out regions. The uniformity of the distribution of quasi-nanoscale bioactive powders.

1, detection method:

The mixture obtained in each example was uniformly placed in the drum shown in Fig. 1. A suitable amount of the composition was taken at each sampling point in the drum shown in Fig. 1 by a sampler, and the taken composition was dissolved in water according to a standard method and the insoluble matter was filtered, and the pH of the filtrate was measured with a precision pH meter.

2. Statistical method: Record the pH value of each sampling point.

3. Test results: See Table 1-1, 1-2, 1-3, 1-4, 1-5, 1-6.

Table 1-1: pH of the composition of Example 1

Sampling point	pH	Sampling point	pH	Sampling point	pH
						A1	8.02	B1	8.08	C1	8.12
A2	8.05	B2	8.05	C2	8.11
						A3	7.91	B3	8.13	C3	8.08
A4	7.98	B4	8.02	C4	8.08
						A5	8.05	B5	8.06	C5	8.05

The results in Table 1-1 show that the standard deviation of the pH of the sample taken at 15 sampling points is only 5.6%.

Table 1-2: pH of the composition of Example 2

Sampling point	pH	Sampling point	pH	Sampling point	pH
						A1	8.16	B1	8.28	C1	8.20
A2	8.18	B2	8.22	C2	8.26
						A3	8.22	B3	8.19	C3	8.28
A4	8.17	B4	8.25	C4	8.24
						A5	8.20	B5	8.18	C5	8.31

The results in Table 1-2 show that the standard deviation of the pH of the sample taken at 15 sampling points is only 4.6%.

Table 1-3: pH of the composition of Example 3

Sampling point	pH	Sampling point	pH	Sampling point	pH
						A1	8.48	B1	8.49	C1	8.60
A2	8.53	B2	8.55	C2	8.45
						A3	8.54	B3	8.60	C3	8.59

A4	8.61	B4	8.62	C4	8.49
						A5	8.50	B5	8.54	C5	8.56

The results in Table 1-3 show that the standard deviation of the pH of the sample taken at 15 sampling points is only 5.3%.

Table 1-4: pH of the composition of Example 4

Sampling point	pH	Sampling point	pH	Sampling point	pH
						A1	8.68	B1	8.78	C1	8.70
A2	8.78	B2	8.75	C2	8.85
						A3	8.84	B3	8.83	C3	8.79
A4	8.81	B4	8.69	C4	8.83
						A5	8.70	B5	8.67	C5	8.62

The results in Table 1-4 show that the standard deviation of the pH of the sample taken at 15 sampling points is only 6.3%.

Table 1-5: pH of the composition of Example 5

Sampling point	pH	Sampling point	pH	Sampling point	pH
						A1	9.41	B1	9.55	C1	9.40
A2	9.45	B2	9.51	C2	9.48
						A3	9.44	B3	9.50	C3	9.50
A4	9.47	B4	9.57	C4	9.53
						A5	9.49	B5	9.48	C5	9.45

The results in Table 1-5 show that the standard deviation of the pH of the sample taken at 15 sampling points is only 4.7%.

Table 1-6: pH of the composition of Example 6

Sampling point	pH	Sampling point	pH	Sampling point	pH
						A1	9.91	B1	9.95	C1	9.90
A2	9.85	B2	9.91	C2	9.88
						A3	9.84	B3	9.90	C3	9.80
A4	9.87	B4	9.87	C4	9.93
						A5	9.89	B5	9.82	C5	9.95

The results in Table 1-6 show that the standard deviation of the pH of the sample taken at 15 sampling points is only 4.4%.

The results show that the quasi-nanoscale bioactive powders are uniformly distributed in the compositions of Examples 1-6 provided by the present invention.

Experimental Example 2: Composition Stability Test

The stability of the composition can be verified by accelerated aging experiments.

1, detection method:

The composition prepared according to the examples was packaged according to the operating procedure, and the composition was placed in a cell culture incubator at a temperature of 59 ° C, a relative humidity of 55%, and stored for 90 days; respectively, at 0 days, 30 days, 60 days, and Samples were taken for 90 days (this is phase 0, 1, 2, and 3), and the appearance and pH of the composition were separately measured.

2. Test results: See Table 2-1, 2-2, 2-3, 2-4, 2-5, 2-6.

Table 2-1: Stability of Example 1

	Exterior	pH value
			Phase 0	Gelatinous, no delamination	8.0±0.2
Phase 1	Gelatinous, no delamination	8.1±0.1
			season2	Gelatinous, no delamination	8.0±0
Phase 3	Gelatinous, no delamination	8.1±0.4

Table 2-2: Stability of Example 2

	Exterior	pH value
			Phase 0	Gelatinous, no delamination	8.2±0.1
Phase 1	Gelatinous, no delamination	8.3±0.2
			season2	Gelatinous, no delamination	8.3±0
Phase 3	Gelatinous, no delamination	8.2±0.2

Table 2-3: Stability of Example 3

	Exterior	pH value
			Phase 0	Gelatinous, no delamination	8.5±0.3
Phase 1	Gelatinous, no delamination	8.6±0.1
			season2	Gelatinous, no delamination	8.4±0.2
Phase 3	Gelatinous, no delamination	8.5±0

Table 2-4: Stability of Example 4

	Exterior	pH value
			Phase 0	Gelatinous, no delamination	8.8±0.3
Phase 1	Gelatinous, no delamination	8.9±0.1
			season2	Gelatinous, no delamination	8.7±0.2
Phase 3	Gelatinous, no delamination	8.9±0

Table 2-5: Stability of Example 5

	Exterior	pH value
			Phase 0	Gelatinous, no delamination	9.2±0.2
Phase 1	Gelatinous, no delamination	9.4±0.1
			season2	Gelatinous, no delamination	9.3±0.3

Phase 3

Gelatinous, no delamination

9.3±0.1

Table 2-6: Stability of Example 6

	Exterior	pH value
			Phase 0	Gelatinous, no delamination	9.6±0.2
Phase 1	Gelatinous, no delamination	9.7±0.1
			season2	Gelatinous, no delamination	9.7±0.3
Phase 3	Gelatinous, no delamination	9.8±0.1

From the above results, it was found that the compositions provided in Examples 1 to 6 exhibited a gel-like appearance without delamination during the period of 0 to 3, and the pH did not change significantly, indicating that the composition remained stable during the period of 0 to 3.

Experimental Example 3: Clinical effect detection of composition for treating dentin hypersensitivity

1, detection method:

1) 40 people with dentine hypersensitivity were randomly divided into 2 groups (Example 2 and Comparative 1), 20 in each group;

2) blowing cold air for 1 s at a distance of 5 mm from the sensitive cheek of the subject, recording the sensitivity (ie pain level);

3) 3 g of the composition provided in Example 2 and Comparative Example 1 were respectively applied to the sensitive tooth surface of the subject, and after 3 minutes, the mouth was rinsed, and the sensitive part of the subject was evaluated by the method of Step 2). Sensitiveness is recorded after the teeth are stimulated;

4) Sensitivity evaluation standard: According to the evaluation standard of Ishikawa Shoji, 3 degrees for stimulation can induce unbearable pain; 2 degrees for stimulation can induce obvious pain, but can be tolerated; 1 degree for stimulation can induce pain less or Discomfort; 0 degrees for cold and mechanical stimulation without pain.

5) Efficacy evaluation criteria:

"Significant effect" is the difference in sensitivity before and after treatment ≥ 2;

"Effective" is the difference in sensitivity before and after treatment is 1;

"Invalid" is the difference in sensitivity before and after treatment is 0;

"Deterioration" is a negative difference in sensitivity before and after treatment.

among them,

Explicit efficiency (%) = significant effect / total treatment × 100%;

Efficacy (%) = (significant + effective) / total treatment × 100%.

2. Test results: See Table 3.

Table 3: Therapeutic effect of dentin hypersensitivity

From the above results, it was found that the sensitivity of the subject before and after the application of the composition provided in Example 2 (i.e., the pain level) was significantly decreased, and the tester did not experience the recovery of the pain level, that is, the pain level was not restored after the decrease. No side effects associated with the composition or side effects of the composition on oral soft tissues were found in the experiment; the composition provided in Comparative Example 1 did not exhibit a significant therapeutic effect.

Experimental Example 4: Detection of bacteriostatic effect

The accumulation of bacteria and products in plaque is the initiator of gingivitis and periodontitis. The inhibition of oral pathogen growth can effectively alleviate periodontal disease, so the bacteriostasis of the composition can be used as It is an important mechanism indicator for relieving and treating periodontitis.

1, detection method:

1) Preparation of samples: Staphylococcus aureus (or other fungi) is inoculated into the sterilized broth medium, and cultured at 35 ° C overnight to prepare a bacterial suspension for use; the original bacterial suspension (mother liquor) is diluted 10 ⁶ cfu / ml was used as the experimental bacterial solution; in the aseptic environment, the composition of Example 3 and the sample of Comparative Example 2 were weighed 1.0 g each, and 10 ml of the sterilized pH 7.0NaCl-peptone buffer was added, respectively. After mixing, add 1 ml of the experimental bacterial solution, and place it in the dark at 20-25 ° C; take 1 ml of the experimental bacterial solution, add 10 ml of pH 7.0 NaCl-peptone buffer, and place it in the dark at 20-25 ° C as a positive control; pH 7.0NaCl-peptone buffer 11 ml, placed in the dark at 20-25 ° C as a negative control;

2) Inhibition of bacteriostasis: After the experimental bacterial liquid was contacted with the compositions provided in Example 3 and Comparative Example 2, respectively, 10 min, 4 h, 1 day, 4 days, 7 days, and 14 days, pH 7.0NaCl-peptone buffer was used. The test solution and the positive control solution were respectively diluted into 10 ^-3 , 10 ^-4 , 10 ^-5 , 10 ^-6 series and counted by the plate method;

The specific steps are as follows: take 1 ml of each sample dilution or positive control dilution, and add to the sterilized plate; pour about 20 ml of trypticase agar medium, shake gently; The pancreatic casein agar medium was cultured in a 33 ° C incubator; after 4 days of culture, the number of colonies was counted, and the average number of colonies of each dilution stage was calculated.

2, statistics and evaluation methods: the number of colonies at each time point = the largest number of colonies in all levels of dilution (average number of colonies × dilution factor); bacteriostatic agent according to the number of colonies at each time point lg value relative to the initial number of colonies lg The degree of reduction of the value was evaluated, wherein the initial colony number (i.e., the number of colonies at 0) was 2.73 × 10 ⁶ cfu/ml, and the same initial bacterial solution was used in the example group and the comparative group.

3. Evaluation criteria: With reference to the pharmacopoeia efficacy of the pharmacopoeia, the lg value of the 14-day colony decreased by not less than 2.0, and the number of colonies did not increase from 14 days to 28 days, and the antibacterial efficacy of the product was judged to be in compliance with the regulations.

4. Test results: See Table 4.

Table 4: Number of colonies

The results in Table 4 show that the number of colonies in Example 3 decreased from 2.73×10 ⁶ to 2.8×10 ⁴ in 10 min, the lg value decreased by 2.0, and the number of colonies decreased to 0 in 10 min to 4 hours, after which the number of colonies remained at 0. It can be judged that the antibacterial efficacy of the composition provided in Example 3 is in compliance with the pharmacopoeia, and its antibacterial activity is very strong; in the comparative group, the number of colonies (3.0×10 ⁶ ) exceeds the initial number of colonies (2.73×10 ⁶ ) in 10 min, The number of colonies increased with the incubation time, and the number of colonies increased by lg. According to the pharmacopoeia, the composition provided in Comparative Example 2 did not have bacteriostatic efficacy. The test results show that the composition provided by the present invention can effectively inhibit the growth of the flora.

Experimental Example 5: Effect of composition on treatment of gingivitis

1, detection method:

1) Using the statistical superiority test design, 62 pairs of samples were included according to clinical experience, 124 cases were enrolled, and the full analysis set (FAS) and the compliance set (PPS) were also examined; the observation period was 28 (±2) days, The baseline was day 0, visit 2 was 14 (±2) days, and visit 3 was 28 (±2) days;

2) Treatment: Subjects after brushing (every morning and evening), take about 4 g of the composition provided in Example 3 (or Comparative Example 2), evenly spread on the edge of the full mouth gum and all the tooth surfaces for 3 minutes. Afterwards, rinse with water;

3) The main efficacy index: sulcus bleeding index (SBI), using the Mazza standard (1981), the researchers used the unified periodontal probe to probe the subject 1mm under the armpit to observe the presence or absence of gums Bleeding and bleeding volume; according to the bleeding of the sulcus, it is divided into 0, 1, 2, 3, 4, 5, a total of 6;

4) Secondary efficacy index: Plaque index (PLI), evaluation of supraorbital plaque using Quigley-Hein standard 1962 (Turesky modified 1970). The plaque staining agent provided by the researcher is used by the researcher and used according to the product description, and is divided into 0, 1, 2, 3, 4, 5 according to the amount of plaque, a total of 6 levels;

5) Effectiveness analysis: sulcus bleeding index (SBI), using the superiority test to compare the 3 sulcus bleeding index compared with the baseline change value, and describe the confidence interval, the test level is unilateral a=0.025; plaque Index (PLI), group-to-group comparison using group t test / Wilcoxon rank sum test;

6) Efficacy analysis: Using the covariance analysis model, the model will consider the test center effect, estimate the corrected mean (LS means) of the mean sulcus bleeding index (SBI), and calculate the difference between the two groups. % confidence interval; in order to examine the consistency between the centers, based on the above-mentioned covariance analysis model, a covariance analysis model with center and group interaction terms will be considered, and whether the interaction term is meaningful at the 0.10 level.

2. Test results: See Table 5-1 and Table 5-2.

Table 5-1: Statistics of sulcus bleeding index

Table 5-2: Plaque Index Statistics

From the above results, after the end of treatment (Visit 3), whether in the FAS episode or in the PPS episode, the P value of the sulcus bleeding index between the visit 3 and the baseline difference group was <0.001. Statistically significant, it showed that the improvement of sulcus bleeding index in the third group was significantly better than that in the comparison 2; the P value of the plaque index between the visit 3 and the baseline difference group was <0.001, which was statistically significant. The improvement in plaque index treatment of the Example 3 group was significantly better than that of Comparative Example 2.

Although the present invention has been described in detail above with the aid of the general description, the specific embodiments and the examples of the invention, it may be obvious to those skilled in the art . Therefore, such modifications or improvements made without departing from the spirit of the invention are intended to be within the scope of the invention.

Claims (10)

1. A composition having multiple oral treatments and health benefits, characterized in that the composition comprises the following components: quasi-nanoscale bioactive mineral powders, protectants, binders, humectants and other ingredients.
2. The composition according to claim 1, wherein the composition comprises the following components by weight: 2 to 50 parts of a quasi-nano-scale bioactive mineral powder, 0.1 to 5 parts of a protective agent, and 0.1 of a binder. ～5 parts, 40 to 80 parts of humectant, and 0.1 to 40 parts of other ingredients.
3. The composition according to claim 1, wherein the composition comprises the following components by weight: 5 to 30 parts of the quasi-nano-scale bioactive mineral powder, 0.2 to 4.5 parts of the protective agent, and 0.2 of the binder. ～3.5 parts, humectant 50-80 parts, and other ingredients 8 to 34 parts.
4. The composition according to any one of claims 1 to 3, wherein the quasi-nano-scale bioactive mineral powder contains the following components by weight: 45 to 61% of SiO ₂ and 17 to 27% of CaO. Na ₂ O 19 to 25%, P ₂ O ₅ 2.6 to 6%; the quasi-nano-scale bioactive mineral powder has a volume of less than 90 μm, wherein the quasi-nano-sized powder having a particle diameter in the range of 100 to 900 nm It accounts for 5-20% of the total powder weight.
5. The composition according to any one of claims 1 to 3, wherein the protective agent is selected from the group consisting of one or a mixture of a water-soluble chitosan derivative or sodium hyaluronate; The mixture is selected from one or more of carbomer, sodium carboxymethylcellulose, guar gum or carrageenan; the humectant is selected from one or more of glycerin, polyethylene glycol or sorbitol. Kind.
6. The composition according to claim 5, wherein the protective agent is a mixture of a chitosan water-soluble derivative and sodium hyaluronate; and the chitosan water-soluble derivative is carboxymethyl chitosan.
7. The composition according to any one of claims 1 to 3, wherein the other component is selected from one or more of a surfactant, a thickener, a sweetener or a flavor; The surfactant is selected from the group consisting of alkyl glycosides, sodium lauryl sulfate, and sucrose One or more of an ester, sodium N-lauroyl sarcosinate or sodium dodecylbenzene sulfonate; the thickener is selected from one or both of silica or magnesium aluminum silicate; The sweetener is selected from one or more of acesulfame, sodium saccharin, erythritol or xylitol; the fragrance is selected from the group consisting of aromatic alcohols, aromatics, and terpenes.
8. The method for preparing a composition according to any one of claims 1 to 7, wherein the method is a method for preparing a vacuum vacuum high-speed emulsification, comprising the steps of: adding under vacuum and high-speed emulsification; Protectant, moisturizer and binder, stir for 5 to 60 minutes, let stand, then obtain the mixture, and then continue to vacuum and high-speed emulsification, according to the formula, quasi-nano-scale bioactive mineral powder and other ingredients The mixture is added to the above mixture, stirred for 5 to 60 minutes, and allowed to stand for 5 to 30 minutes, and the composition is obtained.
9. The preparation method according to claim 8, wherein the method comprises the following steps:

   1) Set the vacuum to -70 ~ -101kPa, high-speed emulsification, stirring speed of 500 ~ 2500 rev / min, scraping wall stirring speed of 5 ~ 80 rev / min, according to the formula added protective agent, moisturizer and bonding Stir, stirring for 5 to 60 minutes;

   2) The vacuum is allowed to stand, and the standing time is 10 to 40 hours, until the mixture is in a uniform solid-liquid mixed phase, that is, the mixture is obtained;

   3) The vacuum degree is set to -70 to -101 kPa, high speed emulsification and agitation, the stirring speed is 500 to 2500 rpm, the wall scraping speed is 5 to 80 rpm, and the product obtained in the step 2) is added according to the formula. Nano-scale bioactive mineral powder and other ingredients, stirred for 5 to 60 minutes;

   4) The product obtained in the step 3) is allowed to stand under vacuum and allowed to stand for 5 to 30 minutes until the mixture is in a uniform viscous paste, and the composition is obtained.
10. Use of the composition according to any one of claims 1 to 9 for the preparation of a medicament or a dental article for the prevention and treatment of dental hypersensitivity, periodontal disease, oral ulcer and plaque rickets.

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