Oral care compositions containing hyaluronic acid and polyphosphates and their applications

Abstract

This invention discloses an oral care composition comprising hyaluronic acid and polyphosphate and its application. The oral care composition includes: 1) hyaluronic acid; 2) polyphosphate; and 3) an orally acceptable carrier. The polyphosphate is one or a combination of two or more of pyrophosphate, tripolyphosphate, or hexametaphosphate. The hyaluronic acid comprises one or a combination of two or more of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, and low molecular weight hyaluronic acid. The pH value of the oral care composition is 6-9. The hyaluronic acid in this oral care composition can improve the stability of the polyphosphate in the composition, and hyaluronic acid also has the effect of improving the stability of the polyphosphate in the oral care composition. Moreover, the oral care composition comprising hyaluronic acid and polyphosphate of this invention also has a good effect on teeth whitening.

Description

Technical Field

[0001] This invention relates to the field of oral care technology, and in particular to an oral care composition comprising hyaluronic acid and polyphosphate and its application. Background Technology

[0002] Polyphosphates such as pyrophosphate, tripolyphosphate, and hexametaphosphate have a long history of use in oral care compositions. They are commonly used as pH adjusters in product formulations or to deliver anti-tartar and teeth whitening effects. However, the stability of polyphosphates is affected by the surrounding environment. For example, the specification of Chinese patent CN97199983.X describes on page 1, line 25: "Some polyphosphates, especially linear polyphosphates with an average chain length greater than 4, can significantly react with most ionic fluoride sources in some oral compositions and change the pH of the oral composition. This reaction impairs the ability of the oral composition to provide stable ionic fluoride and polyphosphates to the oral surface." For example, the study results of the literature "The Hydrolysis of The Condensed Phosphates" (Can. Journal of Chemistry. 1954, 32, 42-47) proved that the stability of pyrophosphate and tripolyphosphate is affected by pH. It showed that the hydrolysis rate of pyrophosphate increases as the pH decreases, while tripolyphosphate is most stable between pH 9 and 10.

[0003] Fluoride is the most commonly used anti-caries active ingredient in oral care. The new national standard stipulates that the pH range of toothpaste should be 5.5-10, and different bases are suitable for different pH values. For example, wintergreen oil is a very popular fragrance in toothpaste, and its main component, methyl salicylate, has a stable pH range of 6-6.5. Therefore, it is necessary to develop a method to improve the stability of polyphosphates in the suitable pH environment of oral care compositions. Summary of the Invention

[0004] The first technical problem to be solved by the present invention is to provide an oral care composition comprising hyaluronic acid and polyphosphate; wherein the hyaluronic acid in the oral care composition can improve the stability of polyphosphate in the pH range of 6-9.

[0005] The second technical problem to be solved by the present invention is to provide an application of hyaluronic acid in oral care compositions to improve the stability of polyphosphates.

[0006] The third technical problem to be solved by the present invention is to provide an application of an oral care composition containing hyaluronic acid and polyphosphate in teeth whitening.

[0007] To solve the first technical problem mentioned above, the present invention adopts the following technical solution:

[0008] An oral care composition comprising hyaluronic acid and polyphosphate, comprising:

[0009] 1) Hyaluronic acid;

[0010] 2) Polyphosphates;

[0011] 3) Oral-acceptable carriers;

[0012] The pH value of the oral care composition is 6-9;

[0013] The polyphosphate is one or a combination of two or more of pyrophosphate, tripolyphosphate or hexametaphosphate;

[0014] The hyaluronic acid comprises one or more of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, and low molecular weight hyaluronic acid.

[0015] The high molecular weight hyaluronic acid has a weight-average molecular weight of 1000-2000 kDa, preferably 1300-1500 kDa; the medium molecular weight hyaluronic acid has a weight-average molecular weight of 200-600 kDa; and the low molecular weight hyaluronic acid has a weight-average molecular weight ≤10 kDa.

[0016] In some embodiments, the pH value of the oral care composition is 6.5-8.5.

[0017] In some embodiments, the high molecular weight hyaluronic acid accounts for 10-50% of the total hyaluronic acid by mass, the medium molecular weight hyaluronic acid accounts for 30-50% of the total hyaluronic acid by mass, and the low molecular weight hyaluronic acid accounts for 20-40% of the total hyaluronic acid by mass.

[0018] In some embodiments, the hyaluronic acid is a combination of medium molecular weight hyaluronic acid and high molecular weight hyaluronic acid, or a combination of medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid.

[0019] In some embodiments, the polyphosphate is one or a combination of two or more of pyrophosphate, tripolyphosphate, or hexametaphosphate.

[0020] In some embodiments, the polyphosphate is a potassium salt, ammonium salt, or sodium salt of polyphosphate.

[0021] In some embodiments, the polyphosphate accounts for 0.5-10% by weight in the oral care composition.

[0022] In some preferred embodiments, the polyphosphate accounts for 1.0-5.0% by weight in the oral care composition.

[0023] In some embodiments, the hyaluronic acid accounts for 0.005-1% of the mass of the oral care composition.

[0024] In some preferred embodiments, the hyaluronic acid accounts for 0.01-0.5% of the mass of the oral care composition.

[0025] In some preferred embodiments, the hyaluronic acid comprises 0.05-0.2% by mass in the oral care composition. In some embodiments, the oral care composition further comprises a fluoride ion source.

[0026] In some preferred embodiments, the fluoride ion source is one or a combination of two or more of stannous fluoride, sodium fluoride, potassium fluoride, amine fluoride, sodium monofluorophosphate, olafon, and zinc fluoride.

[0027] In some preferred embodiments, the fluoride ions in the fluoride ion source account for 0.05-0.2% by weight of the oral care composition.

[0028] In some embodiments, the oral care composition includes mouthwash or liquid toothpaste.

[0029] To address the second technical problem mentioned above, the present invention provides an application of hyaluronic acid in oral care compositions to improve the stability of polyphosphates; wherein the hyaluronic acid comprises one or more of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, and low molecular weight hyaluronic acid;

[0030] The high molecular weight hyaluronic acid has a weight-average molecular weight of 1000-2000 kDa, preferably 1300-1500 kDa; the medium molecular weight hyaluronic acid has a weight-average molecular weight of 200-600 kDa; and the low molecular weight hyaluronic acid has a weight-average molecular weight ≤10 kDa.

[0031] To address the third technical problem mentioned above, the present invention provides an application of an oral care composition comprising hyaluronic acid and polyphosphate in teeth whitening, wherein the hyaluronic acid comprises one or more of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, and low molecular weight hyaluronic acid.

[0032] The high molecular weight hyaluronic acid has a weight-average molecular weight of 1000-2000 kDa, preferably 1300-1500 kDa; the medium molecular weight hyaluronic acid has a weight-average molecular weight of 200-600 kDa; and the low molecular weight hyaluronic acid has a weight-average molecular weight ≤10 kDa.

[0033] Unless otherwise specified, all raw materials used in this invention can be obtained commercially, and the equipment used in this invention can be conventional equipment in the relevant field or refer to existing technology in the relevant field.

[0034] Beneficial effects of the present invention

[0035] This invention provides an oral care composition comprising hyaluronic acid and polyphosphate. The hyaluronic acid in this oral care composition can significantly improve the stability of the polyphosphate in the composition. This invention also provides an application of hyaluronic acid in improving the stability of polyphosphate in oral care compositions. Furthermore, the oral care composition comprising hyaluronic acid and polyphosphate of this invention also has a good effect on teeth whitening. Detailed Implementation

[0036] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0037] Unless otherwise stated, all percentages and ratios used herein are based on the total weight of the composition. Unless otherwise stated, all percentages, proportions, and contents of ingredients mentioned herein are based on the actual content of the ingredient and do not include solvents, fillers, or other substances that can be combined with these ingredients in commercially available products.

[0038] The term "includes / contains" in this article refers to other steps and components that may be added without affecting the final result.

[0039] The term "preferred" and its variations herein refer to embodiments of the invention that provide specific beneficial effects under particular conditions. However, other embodiments may also be preferred under the same or other conditions. Furthermore, the detailed description of one or more preferred embodiments does not imply that other embodiments are useless, nor is it intended to exclude other embodiments from the scope of the invention.

[0040] Unless otherwise specified in the embodiments of the present invention, the conditions shall be performed in accordance with conventional conditions or conditions recommended by the manufacturer; if the manufacturers of the reagents or instruments used are not specified, they are all conventional products that can be purchased commercially.

[0041] As one aspect of the present invention, an oral care composition comprising hyaluronic acid and polyphosphate is provided, comprising:

[0042] 1) Hyaluronic acid;

[0043] 2) Polyphosphates;

[0044] 3) Oral-acceptable carriers;

[0045] The pH value of the oral care composition is 6-9;

[0046] The polyphosphate is one or a combination of two or more of pyrophosphate, tripolyphosphate or hexametaphosphate;

[0047] The hyaluronic acid comprises one or more of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, and low molecular weight hyaluronic acid.

[0048] The high molecular weight hyaluronic acid has a weight-average molecular weight ≥ 1000 kDa, the medium molecular weight hyaluronic acid has a weight-average molecular weight of 200-600 kDa, and the low molecular weight hyaluronic acid has a weight-average molecular weight ≤ 10 kDa.

[0049] The present invention unexpectedly discovered that the hyaluronic acid can significantly improve the stability of polyphosphates in oral care compositions.

[0050] Hyaluronic acid

[0051] Hyaluronic acid, also known as glucuronic acid, is widely distributed throughout the human body. It is a high-molecular-weight polymer polysaccharide composed of D-glucuronic acid and N-acetylglucosamine units. The D-glucuronic acid and N-acetylglucosamine units are linked by β-1,3-glycosidic bonds, and the disaccharide units are linked by β-1,4-glycosidic bonds. The number of disaccharide units can reach as high as 25,000. Its molecular formula is (C... 14 H 21 NO 11 n has the following structure:

[0052]

[0053] The present invention unexpectedly discovered that hyaluronic acid can significantly improve the stability of polyphosphates in oral care compositions, and at the same time enhance the teeth whitening effect of oral care compositions in preventing stains.

[0054] In some embodiments of the present invention, the hyaluronic acid refers to hyaluronic acid salt.

[0055] In some embodiments of the present invention, the hyaluronic acid salt refers to one or more of the sodium, potassium, and ammonium salts of hyaluronic acid.

[0056] In some embodiments of the present invention, the hyaluronic acid is present in the oral care composition at a weight percentage of 0.005-1%, for example, but not limited to 0.01-0.8%, 0.03-0.8%, 0.05-0.8%, 0.08-0.8%, 0.1-0.8%, 0.3-0.8%, 0.5-0.8%, 0.01-0.5%, 0.03-0.5%, 0.05-0.5%, 0.08-0.5%, 0.1-0.5%, 0.3-0.5%, 0.005-0.3%, 0.01-0.3%, 0.03-0.3%, 0.05-0.3%, 0.08-0.3%, 0.1-0.3%, 0.001-0.25%, 0.005-0.25%, 0 0.01-0.25%, 0.03-0.25%, 0.05-0.25%, 0.08-0.25%, 0.1-0.25%, 0.005-0.20%, 0.01-0.20%, 0.03-0.20%, 0.05-0.20%, 0.08-0.20%, 0.1-0.20%, 0.005-0.15%, 0.01-0.15%, 0.03-0.15%, 0.05-0.15%, 0.08-0.15%, 0.1-0.15%, 0.005-0.1%, 0.01-0.1%, 0.03-0.1%, 0.05-0.1%, 0.08-0.1%, 0.01-0.05%, or 0.03-0.05%.

[0057] In some embodiments of the present invention, the weight-average molecular weight of the high molecular weight hyaluronic acid is 1000-2000 kDa, for example 1000-1800 kDa, 1000-1700 kDa, 1000-1500 kDa, 1000-1300 kDa, 1000-1200 kDa, 1000-1100 kDa, 1100-2000 kDa, 1100-1800 kDa, 1100-1700 kDa, 1100-1500 kDa, 1100-1300 kDa, 1100-1200 kDa, 1200-2000 kDa, 1200-1800 kDa, 1200-1700 kDa, 1200-1500 kDa. Da, 1200-1300kDa, 1300-2000kDa, 1300-1800kDa, 1300-1700kDa, 1300-1500kDa, 1000-2000kDa, 1400-2000kDa, 1400-1800kDa, 1400-1700kDa, 1400- 1500kDa, 1500-2000kDa, 1500-1800kDa, 1500-1700kDa, 1600-2000kDa, 1600-1800kDa, 1600-1700kDa, 1700-2000kDa, 1700-1800kDa, 1800-2000kDa.

[0058] In some embodiments of the present invention, the weight-average molecular weight of the medium molecular weight hyaluronic acid is 200-600 kDa, for example 200-550 kDa, 200-500 kDa, 200-450 kDa, 200-400 kDa, 200-350 kDa, 200-300 kDa, 200-250 kDa, 250-550 kDa, 250-500 kDa. 250-450kDa, 250-400kDa, 250-350kDa, 250-300kDa, 300-550kDa, 300-500kDa, 300-4 50kDa, 300-400kDa, 300-350kDa, 350-550kDa, 350-500kDa, 350-450kDa, 350-400kD.

[0059] In some embodiments of the present invention, the weight-average molecular weight of the low molecular weight hyaluronic acid is ≤10 kDa, for example 1-10 kDa, 1-9 kDa, 1-8 kDa, 1-7 kDa, 1-6 kDa, 1-5 kDa, 1-4 kDa, 1-3 kDa, 1-2 kDa, 2-10 kDa, 2-9 kDa, 2-8 kDa, 2-7 kDa, 2-6 kDa, 2-5 kDa, 2-4 kDa, 2-3 kDa, 3-10 kDa, 3-9 kDa, 3-8 KDa, 3-7KDa, 3-6KDa, 3-5KDa, 3-4KDa, 4-10KDa, 4-9KDa, 4-8KDa, 4-7KDa, 4-6KDa, 4-5KDa, 5-10KDa, 5-9KDa a, 5-8KDa, 5-7KDa, 5-6KDa, 6-10KDa, 6-9KDa, 6-8KDa, 6-7KDa, 7-10KDa, 7-9KDa, 7-8KDa, 8-10KDa, 8-9KDa.

[0060] In some embodiments of the present invention, the high molecular weight hyaluronic acid accounts for 10-50% of the mass of the hyaluronic acid, for example, 10-45%, 10-40%, 10-35%, 10-30%, 10-25%, 10-20%, 10-15%, 15-45%, 15-40%, 15-35%, 15-30%, 15-25%, 15-20%, 20-45%, 20-40%, 20-35%, 20-30%, 20-25%, 25-45%, 25-40%, 25-35%, 25-30%, 30-45%, 30-40%, 30-35%.

[0061] In some embodiments of the present invention, the medium molecular weight hyaluronic acid accounts for 30-50% of the total mass of the hyaluronic acid, for example, 30-48%, 30-45%, 30-42%, 30-40%, 30-38%, 30-35%, 30-33%, 33-50%, 33-48%, 33-48%, 33-45%, 33-42%, 33-40%, 33-38%, 33-35%, 35-50%, 35-48%, 35-45%, 35-42%, 35-40%, 35-38%, 38-50%, 38-48%, 38-45%, 38-42%, 38-40%, 40-50%, 40-48%, 40-45%, 40-42%, 43-50%, 43-48%, 43-45%, 45-50%, 45-48%.

[0062] In some embodiments of the present invention, the low molecular weight hyaluronic acid accounts for 20-40% of the total mass of the hyaluronic acid, for example, 20-38%, 20-35%, 20-32%, 20-30%, 20-28%, 20-25%, 20-22%, 22-38%, 22-35%, 22-32%, 22-30%, 22-28%, 22-25%, 25-38%, 25-35%, 25-32%, 25-30%, 25-28%, 28-38%, 28-35%, 28-32%, 28-30%, 30-38%, 30-35%, 30-32%, 32-38%, 32-35%.

[0063] Polyphosphate

[0064] The polyphosphates described in this invention are one or a combination of two or more of pyrophosphates, tripolyphosphates, or hexametaphosphates. They can be used in oral care compositions as pH adjusters, teeth whitening agents, or anti-tartar agents.

[0065] In some embodiments of the present invention, the polyphosphate is an acid salt of polyphosphate.

[0066] In some embodiments of the present invention, the polyphosphate is a potassium salt, sodium salt or ammonium salt of polyphosphate.

[0067] In some embodiments of the present invention, the polyphosphate is sodium pyrophosphate, sodium hydrogen pyrophosphate, disodium dihydrogen pyrophosphate, potassium pyrophosphate, potassium hydrogen pyrophosphate, dimethyl dihydrogen pyrophosphate, sodium tripolyphosphate, potassium tripolyphosphate, sodium hexametaphosphate, or potassium hexametaphosphate.

[0068] In some embodiments of the invention, the polyphosphate is present in the oral care composition at a weight percentage of 0.5-10%, for example, but not limited to 0.5-8%, 0.5-6%, 0.5-5%, 0.5-4.5%, 0.5-4%, 0.5-3.5%, 0.5-3%, 0.5-2.5%, 0.5-2%, 0.5-1.5%, 0.5-1%, 0.5-0.8%, 1-10%, 1-8%, 1-6%, 1-5%, 1-4%, 1-3.5%, 1-3%. 1-2.5%, 1-2%, 1-1.5%, 1-1.2%, 2-10%, 2-8%, 2-6%, 2-5%, 2-4.5%, 2-4%, 2-3.5%, 2-3%, 2-2.5%, 3%-10%, 3-8%, 3-6%, 3-5%, 3-4.5%, 3-4%, 3-3.5%, 4-10%, 4-8%, 4-6%, 4-5%, 5-10%, 5-8%, 5-6%, 6-10%, 6-8%, 6-10%, 8-10%.

[0069] Fluoride ion source

[0070] In some embodiments of the invention, the oral care composition further includes a fluoride ion source.

[0071] In some preferred embodiments of the present invention, the fluoride ion source is derived from one or more of stannous fluoride, sodium fluoride, potassium fluoride, amine fluoride, sodium monofluorophosphate, olafon, and zinc fluoride.

[0072] The present invention unexpectedly discovered that when an oral care composition contains both a fluoride ion source and polyphosphate, the addition of hyaluronic acid to the composition results in a higher rate of increase in polyphosphate retention.

[0073] In some embodiments of the present invention, the weight percentage of fluoride ions in the fluoride ion source in the oral care composition is 0.05-0.2%, for example, but not limited to 0.08-0.2%, 0.1-0.2%, 0.15-0.2%, 0.05-0.15%, 0.08-0.15%, and 0.1-0.15%.

[0074] pH

[0075] The inventors unexpectedly discovered that maintaining the pH of an oral care composition containing polyphosphates and hyaluronic acid between 6 and 9 can significantly improve the stability of polyphosphates in the composition and inhibit their hydrolysis.

[0076] In some embodiments of the present invention, the pH range of the composition is 6-9, such as, but not limited to, 6.5-9, 7-9, 7.5-9, 8-9, 8.5-9, 6.5-9, 6-8.5, 6.5-8.5, 7-8.5, 7.5-8.5, 8-8.5, 6-8, 6.5-8, 7-8, 7.5-8, 6-7.5, 6.5-7.5, 7-7.5, 6-7, 6.5-7, 6-6.5.

[0077] In some embodiments of the present invention, the pH adjuster includes, but is not limited to, one or more of sodium hydroxide, hydrochloric acid, sulfuric acid, citric acid and its salts, lactic acid and its salts, phosphoric acid and its salts, phthalic acid and its salts, citric acid and its salts, and acetic acid and its salts.

[0078] Other oral acceptable carriers

[0079] In some embodiments of the present invention, the oral care composition is liquid toothpaste or mouthwash.

[0080] In this invention, "orally acceptable carrier" refers to any medium suitable for formulating the oral care compositions disclosed herein; an orally acceptable carrier is harmless to mammals when held in the mouth in the amount disclosed herein without being swallowed for a duration sufficient to allow effective contact with the tooth surface as required by the invention; generally, an orally acceptable carrier is not harmful even if unintentionally swallowed; suitable orally acceptable carriers include, for example, one or more of the following substances: water, abrasives, surfactants, thickeners, pH adjusters, humectants, flavorings, visual aids (e.g., pigments, dyes or mixtures thereof), anti-caries agents, antibacterial agents, whitening agents, desensitizing agents, preservatives, and mixtures thereof.

[0081] In some embodiments, the oral care composition includes mouthwash or liquid toothpaste.

[0082] As another aspect of the invention, the present invention provides an application of hyaluronic acid in oral care compositions to improve the stability of polyphosphates; said hyaluronic acid comprises one or more of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid.

[0083] The high molecular weight hyaluronic acid has a weight-average molecular weight of 1000-2000 kDa, preferably 1300-1500 kDa; the medium molecular weight hyaluronic acid has a weight-average molecular weight of 200-600 kDa; and the low molecular weight hyaluronic acid has a weight-average molecular weight ≤10 kDa.

[0084] As another aspect of the invention, the present invention provides the application of an oral care composition comprising hyaluronic acid and polyphosphate in teeth whitening; wherein the hyaluronic acid comprises one or more of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid.

[0085] The high molecular weight hyaluronic acid has a weight-average molecular weight of 1000-2000 kDa, preferably 1300-1500 kDa; the medium molecular weight hyaluronic acid has a weight-average molecular weight of 200-600 kDa; and the low molecular weight hyaluronic acid has a weight-average molecular weight ≤10 kDa.

[0086] The method for calculating the growth rate of polyphosphate retention in this application

[0087] 1) Prepare a composition containing polyphosphate as a reference standard;

[0088] 2) Prepare a composition with the same polyphosphate weight ratio and added hyaluronic acid as a test sample;

[0089] 3) Detect the weight ratio of polyphosphate in the control and test samples after aging, i.e. the amount of polyphosphate retained in the composition;

[0090] 4) Calculate the growth rate of the retention:

[0091] Specific Implementation

[0093] HA-1 to HA-9 are the hyaluronic acid raw materials used in the examples.

[0094] Table 1 shows nine different hyaluronic acid raw materials containing different molecular weight ranges.

[0095] Table 1: (Percentages in the table are by weight)

[0096]

[0097] In other words,

[0098] HA-1 is a low molecular weight hyaluronic acid raw material with a weight-average molecular weight in the range of 1-10 kDa;

[0099] HA-2 is a medium molecular weight hyaluronic acid raw material with a weight-average molecular weight in the range of 200-600 kDa;

[0100] HA-3 is a high molecular weight hyaluronic acid raw material with a weight-average molecular weight in the range of 1000-2000 kDa;

[0101] HA-4 is a mixed raw material containing 50% low molecular weight hyaluronic acid with a weight average molecular weight in the range of 1-10 kDa and 50% high molecular weight hyaluronic acid with a weight average molecular weight in the range of 1000-2000 kDa.

[0102] HA-5 is a mixed raw material containing 50% low molecular weight hyaluronic acid with a weight average molecular weight in the range of 1-10 kDa and 50% medium molecular weight hyaluronic acid with a weight average molecular weight in the range of 200-600 kDa.

[0103] HA-6 is a mixed raw material containing 50% medium molecular weight hyaluronic acid with a weight average molecular weight in the range of 200-600 kDa and 50% high molecular weight hyaluronic acid with a weight average molecular weight in the range of 1000-2000 kDa.

[0104] HA-7 is a mixture of raw materials containing 20% ​​low molecular weight hyaluronic acid with a weight average molecular weight in the range of 1-10 kDa, 30% medium molecular weight hyaluronic acid with a weight average molecular weight in the range of 200-600 kDa, and 50% high molecular weight hyaluronic acid with a weight average molecular weight in the range of 1000-2000 kDa.

[0105] HA-8 is a mixture of raw materials containing 40% low molecular weight hyaluronic acid with a weight average molecular weight in the range of 1-10 kDa, 50% medium molecular weight hyaluronic acid with a weight average molecular weight in the range of 200-600 kDa, and 10% high molecular weight hyaluronic acid with a weight average molecular weight in the range of 1000-2000 kDa.

[0106] HA-9 is a raw material containing 40% low molecular weight hyaluronic acid with a weight average molecular weight in the range of 1-10 kDa, 40% medium and low molecular weight hyaluronic acid with a weight average molecular weight in the range of 200-600 kDa, and 20% high molecular weight hyaluronic acid with a weight average molecular weight in the range of 1000-2000 kDa.

[0107] Basic recipe 1-10

[0108] Prepare basic formulas 1-10 according to Table 2. All data in the table are weight percentages.

[0109] Table 2:

[0110]

[0111] As can be seen from Table 2:

[0112] Basic formulation 1 is an aqueous solution of sodium pyrophosphate at a weight ratio of 1%;

[0113] Basic Formula 2 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-1 type hyaluronic acid.

[0114] Basic Formula 3 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-2 type hyaluronic acid.

[0115] Basic Formula 4 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-3 hyaluronic acid.

[0116] Basic Formula 5 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-4 type hyaluronic acid.

[0117] Basic Formula 6 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-5 hyaluronic acid.

[0118] Basic Formula 7 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-6 hyaluronic acid.

[0119] Basic Formula 8 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-7 hyaluronic acid.

[0120] Basic Formula 9 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-8 hyaluronic acid.

[0121] Basic Formula 10 is based on Basic Formula 1 with the addition of 0.05% by weight of HA-9 hyaluronic acid.

[0122] Examples 1-9, Comparative Example 1

[0123] Comparative Example 1: The pH of Basic Formula 1 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 1.

[0124] Example 1: The pH value of the basic formula 2 was adjusted to 7 with hydrochloric acid to obtain Example 1.

[0125] Example 2: The pH value of the basic formula 3 was adjusted to 7 with hydrochloric acid to obtain Example 2.

[0126] Example 3: The pH value of the basic formula 4 was adjusted to 7 with hydrochloric acid to obtain Example 3.

[0127] Example 4: The pH of the basic formula 5 was adjusted to 7 with hydrochloric acid to obtain Example 4.

[0128] Example 5: The pH of the basic formula 6 was adjusted to 7 with hydrochloric acid to obtain Example 5.

[0129] Example 6: The pH value of the basic formula 7 was adjusted to 7 with hydrochloric acid to obtain Example 6.

[0130] Example 7: The pH of the basic formula 8 was adjusted to 7 with hydrochloric acid to obtain Example 7.

[0131] Example 8: The pH value of the basic formula 9 was adjusted to 7 with hydrochloric acid to obtain Example 8.

[0132] Example 9: The pH value of the basic formula 10 was adjusted to 7 with hydrochloric acid to obtain Example 9.

[0133] Examples 1-9 and Comparative Example 1 were aged at 40°C for 3 months. The mass ratio of pyrophosphate retained in the formulation was measured. Comparative Example 1 was used as a control, and the growth rate of pyrophosphate retention in Examples 1-9 was calculated. The results are shown in Table 3.

[0134] Table 3:

[0135]

[0136] As can be seen from Table 3, hyaluronic acid of different molecular weights can improve the stability of pyrophosphate. When hyaluronic acid of medium molecular weight is mixed with hyaluronic acid of low molecular weight or high molecular weight to form mixed hyaluronic acid, the growth rate of pyrophosphate retention increases. In particular, when the molecular weights of the three molecular weights are mixed, the growth rate of retention is the best.

[0137] Comparative Examples 2-3

[0138] Comparative Example 2: The pH of Basic Formula 1 was adjusted to 5.5 with hydrochloric acid to obtain Comparative Example 2.

[0139] Comparative Example 3: The pH of Basic Formula 10 was adjusted to 5.5 with hydrochloric acid to obtain Comparative Example 3.

[0140] Comparative Examples 2 and 3 were aged at 40℃ for 3 months, and the weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 2 was used as a control, and the growth rate of pyrophosphate retention in Comparative Example 3 was calculated. The results are shown in Table 4.

[0141] Table 4:

[0142] Comparative Example 3 growth rate of retention -2.96％ pH value 5.5

[0143] As can be seen from Table 4:

[0144] When 0.05% HA-9 was added to a 1% by weight sodium pyrophosphate solution and the pH was adjusted to 5.5, the growth rate of pyrophosphate retention was -2.96%. This means that under the condition of pH adjustment to 5.5, compared with the control group, HA-9 did not show a stabilizing effect on pyrophosphate, but instead accelerated the hydrolysis of pyrophosphate.

[0145] Example 10, Comparative Example 4

[0146] Comparative Example 4: The pH of Basic Formula 1 was adjusted to 6 with hydrochloric acid to obtain Comparative Example 4.

[0147] Example 10: The pH value of the basic formula 10 was adjusted to 6 with hydrochloric acid to obtain Example 10.

[0148] Example 10 and Comparative Example 4 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 4 was used as a control, and the growth rate of pyrophosphate retention in Example 10 was calculated. The results are shown in Table 5.

[0149] Table 5:

[0150] Example 10 growth rate of retention 1.56％ pH value 6

[0151] As can be seen from Table 5:

[0152] When 0.05% HA-9 was added to a 1% by weight sodium pyrophosphate solution and the pH was adjusted to 6, the pyrophosphate retention increased by 1.56%, which was an increase, but the increase was small. That is, under the condition of pH adjustment to 6, compared with the control group, HA-9 can improve the stability of pyrophosphate, but the increase is not significant.

[0153] Example 11, Comparative Example 5

[0154] Comparative Example 5: The pH of Basic Formula 1 was adjusted to 6.5 with hydrochloric acid to obtain Comparative Example 5.

[0155] Example 11: The pH value of the basic formula 10 was adjusted to 6.5 with hydrochloric acid to obtain Example 11.

[0156] Example 11 and Comparative Example 5 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 5 was used as a control, and the growth rate of pyrophosphate retention in Example 11 was calculated. The results are shown in Table 6.

[0157] Table 6:

[0158] Example 11 growth rate of retention 20.21％ pH value 6.5

[0159] As can be seen from Table 6:

[0160] When 0.05% HA-9 was added to a 1% by weight sodium pyrophosphate solution and the pH was adjusted to 6.5, the pyrophosphate retention increased by 20.21%, meaning that under pH adjustment to 6.5, the stability of pyrophosphate was significantly improved compared to the control group HA-9.

[0161] Example 12, Comparative Example 6

[0162] Comparative Example 6: The pH of Basic Formula 1 was adjusted to 7.5 with hydrochloric acid to obtain Comparative Example 6.

[0163] Example 12: The pH of the basic formula 10 was adjusted to 7.5 with hydrochloric acid to obtain Example 12.

[0164] Example 12 and Comparative Example 6 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 6 was used as a control, and the growth rate of pyrophosphate retention in Example 12 was calculated. The results are shown in Table 7.

[0165] Table 7:

[0166] Example 12 growth rate of retention 33.61％ pH value 7.5

[0167] As can be seen from Table 7:

[0168] When 0.05% HA-9 was added to a 1% by weight sodium pyrophosphate solution and the pH was adjusted to 7.5, the pyrophosphate retention increased by 33.61%; that is, under the condition of pH adjustment to 7.5, the stability of pyrophosphate can be significantly improved compared with the control group HA-9.

[0169] Example 13, Comparative Example 7

[0170] Comparative Example 7: The pH of Basic Formula 1 was adjusted to 8 with hydrochloric acid to obtain Comparative Example 7.

[0171] Example 13: The pH value of the basic formula 10 was adjusted to 8 with hydrochloric acid to obtain Example 13.

[0172] Example 13 and Comparative Example 7 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 7 was used as a control, and the growth rate of pyrophosphate retention in Example 13 was calculated. The results are shown in Table 8.

[0173] Table 8:

[0174] Example 13 growth rate of retention 25.22％ pH value 8

[0175] As shown in Table 8, when 0.05% HA-9 was added to a 1% sodium pyrophosphate solution and the pH was adjusted to 8, the pyrophosphate retention increased by 25.22%. This means that under the condition of pH adjustment to 8, the stability of pyrophosphate can be significantly improved compared with the control group HA-9.

[0176] Example 14, Comparative Example 8

[0177] Comparative Example 8: The pH of Basic Formula 1 was adjusted to 8.5 with hydrochloric acid to obtain Comparative Example 8.

[0178] Example 14: The pH value of the basic formula 10 was adjusted to 8.5 with hydrochloric acid to obtain Example 14.

[0179] Example 14 and Comparative Example 8 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 8 was used as a control, and the growth rate of pyrophosphate retention in Example 14 was calculated. The results are shown in Table 9.

[0180] Table 9:

[0181] Example 14 growth rate of retention 12.14％ pH value 8.5

[0182] As can be seen from Table 12, when 0.05% HA-9 is added to a 1% by weight sodium pyrophosphate solution and the pH is adjusted to 8.5, the growth rate of pyrophosphate retention is 12.14%, which means that under the condition of pH adjustment to 8.5, the stability of pyrophosphate can still be improved compared with the control group HA-9.

[0183] Example 15, Comparative Example 9

[0184] Comparative Example 9: The pH of Basic Formula 1 was adjusted to 9 with hydrochloric acid to obtain Comparative Example 9.

[0185] Example 15: The pH of the basic formula 10 was adjusted to 9 with hydrochloric acid to obtain Example 15.

[0186] Example 15 and Comparative Example 9 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 9 was used as a control, and the growth rate of pyrophosphate retention in Example 15 was calculated. The results are shown in Table 10.

[0187] Table 10:

[0188] Example 15 growth rate of retention 1.03％ pH value 9

[0189] As can be seen from Table 10:

[0190] When 0.05% HA-9 was added to a 1% by weight sodium pyrophosphate solution and the pH was adjusted to 9, the pyrophosphate retention increased by 1.03%. This means that, under pH 9 conditions, although HA-9 can still improve the stability of pyrophosphate compared to the control group, the improvement is limited.

[0191] As shown in Table 1-10 above, adding 0.05% HA-9 to a 1% (by weight) sodium pyrophosphate solution can improve the stability of pyrophosphate when the pH is 6-9; and can significantly improve the stability of pyrophosphate when the pH is 6.5-8.5.

[0192] Basic formula 11-12

[0193] Prepare basic formula 11 and basic formula 12 according to Table 11. All data in the table are weight percentages.

[0194] Table 11

[0195] Raw material name Basic Recipe 11 Basic recipe 12 HA-9 / 0.01 Sodium pyrophosphate 0.5 0.5 Deionized water Add to 100% Add to 100%

[0196] As can be seen from Table 11:

[0197] Basic formulation 11 is a 0.5% sodium pyrophosphate aqueous solution by weight;

[0198] The basic formulation 12 is a mixed aqueous solution of sodium pyrophosphate at a weight ratio of 0.5% and HA-9 at a weight ratio of 0.01%.

[0199] Example 16, Comparative Example 10

[0200] Comparative Example 10: The pH of Basic Formula 11 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 10.

[0201] Example 16: The pH of the basic formula 12 was adjusted to 7 with hydrochloric acid to obtain Example 16.

[0202] Example 16 and Comparative Example 10 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 10 was used as a control, and the growth rate of pyrophosphate retention in Example 16 was calculated. The results are shown in Table 12.

[0203] Table 12:

[0204] Example 16 growth rate of retention 37.39％ pH value 7

[0205] As can be seen from Table 12:

[0206] When 0.01% HA-9 was added to a 0.5% sodium pyrophosphate solution and the pH was adjusted to 7, the pyrophosphate retention increased by 37.39%. This means that under pH adjustment to 7, 0.01% HA-9 significantly improved the stability of 0.5% sodium pyrophosphate.

[0207] Basic recipe 13-14

[0208] Prepare basic formula 13 and basic formula 14 according to Table 13. All data in the table are weight percentages.

[0209] Table 13

[0210] Raw material name Basic Recipe 13 Basic Recipe 14 HA-9 / 0.5 Sodium pyrophosphate 10 10 Deionized water Add to 100% Add to 100%

[0211] As can be seen from Table 13:

[0212] Basic formulation 13 is a 10% sodium pyrophosphate aqueous solution by weight;

[0213] The basic formulation 14 is a mixed aqueous solution of sodium pyrophosphate at a weight ratio of 10% and HA-9 at a weight ratio of 0.5%.

[0214] Example 17, Comparative Example 11

[0215] Comparative Example 11: The pH of Basic Formula 13 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 11.

[0216] Example 17: The pH of the basic formula 14 was adjusted to 7 with hydrochloric acid to obtain Example 17.

[0217] Example 17 and Comparative Example 11 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 11 was used as a control, and the growth rate of pyrophosphate retention in Example 17 was calculated. The results are shown in Table 14.

[0218] Table 14:

[0219] Example 17 growth rate of retention 29.33％ pH value 7

[0220] As can be seen from Table 14:

[0221] When 0.5% HA-9 was added to a 10% sodium pyrophosphate solution and the pH was adjusted to 7, the pyrophosphate retention increased by 29.33%. This means that under the condition of pH adjustment to 7, 0.5% HA-9 also significantly improved the stability of 10% sodium pyrophosphate.

[0222] Basic formula 15-16

[0223] Prepare basic formula 15 and basic formula 16 according to Table 15. All data in the table are weight percentages.

[0224] Table 15

[0225] Raw material name Basic recipe 15 Basic Recipe 16 HA-9 / 0.05 Sodium tripolyphosphate 1.0 1.0 Deionized water Add to 100% Add to 100%

[0226] As can be seen from Table 15:

[0227] The basic formula 15 is a 1% sodium tripolyphosphate aqueous solution by weight;

[0228] The basic formulation 16 is a mixed aqueous solution of 1% sodium tripolyphosphate and 0.05% HA-9 by weight.

[0229] Comparative Examples 12-13

[0230] Comparative Example 12: The pH of Basic Formula 15 was adjusted to 5.5 with hydrochloric acid to obtain Comparative Example 12.

[0231] Comparative Example 13: The pH of Basic Formula 16 was adjusted to 5.5 with hydrochloric acid to obtain Comparative Example 13.

[0232] Comparative Examples 12 and 13 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 12 was used as a control, and the growth rate of tripolyphosphate retention in Comparative Example 13 was calculated. The results are shown in Table 16.

[0233] Example 18, Comparative Example 14

[0234] Comparative Example 14: The pH of the basic formula 15 was adjusted to 6 with hydrochloric acid to obtain Comparative Example 14.

[0235] Example 18: The pH of the basic formula 16 was adjusted to 6 with hydrochloric acid to obtain Example 18.

[0236] Comparative Example 14 and Example 18 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 14 was used as a control, and the growth rate of tripolyphosphate retention in Example 18 was calculated. The results are shown in Table 16.

[0237] Example 19, Comparative Example 15

[0238] Comparative Example 15: The pH of Basic Formula 15 was adjusted to 6.5 with hydrochloric acid to obtain Comparative Example 15.

[0239] Example 19: The pH of the basic formula 16 was adjusted to 6.5 with hydrochloric acid to obtain Example 19.

[0240] Comparative Example 15 and Example 19 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 15 was used as a control, and the growth rate of tripolyphosphate retention in Example 19 was calculated. The results are shown in Table 16.

[0241] Example 20, Comparative Example 16

[0242] Comparative Example 16: The pH of Basic Formula 15 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 16.

[0243] Example 20: The pH of the basic formula 16 was adjusted to 7 with hydrochloric acid to obtain Example 20.

[0244] Comparative Example 16 and Example 20 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 16 was used as a control, and the growth rate of tripolyphosphate retention in Example 20 was calculated. The results are shown in Table 16.

[0245] Example 21, Comparative Example 17

[0246] Comparative Example 17: The pH of Basic Formula 15 was adjusted to 8 with hydrochloric acid to obtain Comparative Example 17.

[0247] Example 21: The pH value of the basic formula 16 was adjusted to 8 with hydrochloric acid to obtain Example 21.

[0248] Comparative Example 17 and Example 21 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 17 was used as a control, and the growth rate of tripolyphosphate retention in Example 21 was calculated. The results are shown in Table 16.

[0249] Example 22, Comparative Example 18

[0250] Comparative Example 18: The pH of Basic Formula 15 was adjusted to 8.5 with hydrochloric acid to obtain Comparative Example 18.

[0251] Example 22: The pH value of the basic formula 16 was adjusted to 8.5 with hydrochloric acid to obtain Example 22.

[0252] Comparative Example 18 and Example 22 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 18 was used as a control, and the growth rate of tripolyphosphate retention in Example 22 was calculated. The results are shown in Table 16.

[0253] Example 23, Comparative Example 19

[0254] Comparative Example 19: The pH of Basic Formula 15 was adjusted to 9 with hydrochloric acid to obtain Comparative Example 19.

[0255] Example 23: The pH value of the basic formula 16 was adjusted to 9 with hydrochloric acid to obtain Example 23.

[0256] Comparative Example 19 and Example 23 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 19 was used as a control, and the growth rate of tripolyphosphate retention in Example 23 was calculated. The results are shown in Table 16.

[0257] Table 16: Growth rate (%) of tripolyphosphate retention in Examples 18-23 and Comparative Example 13

[0258] Comparative Example 13 Example 18 Example 19 Example 20 Example 21 Example 22 Example 23 pH value 5.5 6 6.5 7 8 8.5 9 growth rate of retention 1.92 8.01 25.28 36.33 26.51 14.99 4.73

[0259] Table 16 shows that:

[0260] Within the pH range of 5.5-9, HA-9 can improve the stability of tripolyphosphate; the improvement is more significant, especially at pH 6.5-8.5.

[0261] Basic formula 17-18

[0262] Prepare basic formula 17 and basic formula 18 according to Table 17. All data in the table are weight percentages.

[0263] Table 17

[0264] Raw material name Basic Recipe 17 Basic Recipe 18 HA-9 / 0.01 Sodium tripolyphosphate 0.5 0.5 Deionized water Add to 100% Add to 100%

[0265] As can be seen from Table 17:

[0266] The basic formula 17 is a 0.5% sodium tripolyphosphate aqueous solution.

[0267] The basic formulation 18 is a mixed aqueous solution of 0.5% sodium tripolyphosphate and 0.01% HA-9.

[0268] Example 24, Comparative Example 20

[0269] Comparative Example 20: The pH of Basic Formula 17 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 20.

[0270] Example 24: The pH of the basic formula 18 was adjusted to 7 with hydrochloric acid to obtain Example 24.

[0271] Example 24 and Comparative Example 20 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 20 was used as a control, and the growth rate of tripolyphosphate retention in Example 24 was calculated. The results are shown in Table 18.

[0272] Table 18:

[0273] Example 24 growth rate of retention 39.97％ pH value 7

[0274] As can be seen from Table 18:

[0275] When 0.01% HA-9 was added to a 0.5% sodium tripolyphosphate solution and the pH was adjusted to 7, the growth rate of tripolyphosphate retention was 39.97%; that is, under the condition of pH adjustment to 7, 0.01% HA-9 also significantly improved the stability of 0.5% sodium tripolyphosphate.

[0276] Basic formula 19-20

[0277] Prepare basic formula 19 and basic formula 20 according to Table 19. All data in the table are weight percentages.

[0278] Table 19:

[0279] Raw material name Basic Recipe 19 Basic recipe 20 HA-9 / 0.5 Sodium tripolyphosphate 10 10 Deionized water Add to 100% Add to 100%

[0280] As can be seen from Table 19:

[0281] The basic formula 19 is a 10% sodium tripolyphosphate aqueous solution;

[0282] The basic formulation 20 is a mixed aqueous solution of 10% sodium tripolyphosphate and 0.5% HA-9.

[0283] Example 25, Comparative Example 21

[0284] Comparative Example 21: The pH of Basic Formula 19 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 21.

[0285] Example 25: The pH of the basic formula 20 was adjusted to 7 with hydrochloric acid to obtain Example 25.

[0286] Example 25 and Comparative Example 21 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 21 was used as a control, and the growth rate of tripolyphosphate retention in Example 25 was calculated. The results are shown in Table 20.

[0287] Table 20:

[0288] Example 25 growth rate of retention 32.65％ pH value 7

[0289] As can be seen from Table 20:

[0290] When 0.5% HA-9 was added to a 10% sodium tripolyphosphate solution and the pH was adjusted to 7, the growth rate of tripolyphosphate retention was 32.65%; that is, under the condition of pH adjustment to 7, 0.5% HA-9 also significantly improved the stability of 10% sodium tripolyphosphate.

[0291] Basic recipe 21-22

[0292] Prepare basic formula 21 and basic formula 22 according to Table 21. All data in the table are weight percentages.

[0293] Table 21

[0294] Raw material name Basic Recipe 21 Basic Recipe 22 HA-9 / 0.05 Sodium hexametaphosphate 1.0 1.0 Deionized water Add to 100% Add to 100%

[0295] As can be seen from Table 21:

[0296] Basic formula 21 is an aqueous solution of sodium hexametaphosphate at a weight ratio of 1%.

[0297] Basic Formula 22 is based on Basic Formula 13 with the addition of 0.05% HA-9 by weight.

[0298] Comparative Examples 22-23

[0299] Comparative Example 22: The pH of the basic formula 21 was adjusted to 5.5 with hydrochloric acid to obtain Comparative Example 22.

[0300] Comparative Example 23: The pH of the basic formula 22 was adjusted to 5.5 with hydrochloric acid to obtain Comparative Example 23.

[0301] Comparative Examples 22 and 23 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 22 was used as a control, and the growth rate of hexametaphosphate retention in Comparative Example 23 was calculated. The results are shown in Table 22.

[0302] Example 26, Comparative Example 24

[0303] Comparative Example 24: The pH of Basic Formula 21 was adjusted to 6 with hydrochloric acid to obtain Comparative Example 24.

[0304] Example 26: The pH value of the basic formula 22 was adjusted to 6 with hydrochloric acid to obtain Example 26.

[0305] Comparative Example 24 and Example 26 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 24 was used as a control, and the growth rate of hexametaphosphate retention in Example 26 was calculated. The results are shown in Table 22.

[0306] Example 27, Comparative Example 25

[0307] Comparative Example 25: The pH of Basic Formula 21 was adjusted to 6.5 with hydrochloric acid to obtain Comparative Example 25.

[0308] Example 27: The pH of the basic formula 22 was adjusted to 6.5 with hydrochloric acid to obtain Example 27.

[0309] Comparative Example 25 and Example 27 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 25 was used as a control, and the growth rate of hexametaphosphate retention in Example 27 was calculated. The results are shown in Table 22.

[0310] Example 28, Comparative Example 26

[0311] Comparative Example 26: The pH of Basic Formula 21 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 26.

[0312] Example 28: The pH of the basic formula 22 was adjusted to 7 with hydrochloric acid to obtain Example 28.

[0313] Comparative Example 26 and Example 28 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 26 was used as a control, and the growth rate of hexametaphosphate retention in Example 28 was calculated. The results are shown in Table 22.

[0314] Example 29, Comparative Example 27

[0315] Comparative Example 27: The pH of Basic Formula 21 was adjusted to 8 with hydrochloric acid to obtain Comparative Example 27.

[0316] Example 29: The pH of the basic formula 22 was adjusted to 8 with hydrochloric acid to obtain Example 29.

[0317] Comparative Example 27 and Example 29 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 27 was used as a control, and the growth rate of hexametaphosphate retention in Example 29 was calculated. The results are shown in Table 22.

[0318] Example 30, Comparative Example 28

[0319] Comparative Example 28: The pH of the basic formula 21 was adjusted to 8.5 with hydrochloric acid to obtain Comparative Example 28.

[0320] Example 30: The pH value of the basic formula 22 was adjusted to 8.5 with hydrochloric acid to obtain Example 30.

[0321] Comparative Example 28 and Example 30 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 28 was used as a control, and the growth rate of hexametaphosphate retention in Example 30 was calculated. The results are shown in Table 22.

[0322] Example 31, Comparative Example 29

[0323] Comparative Example 29: The pH of Basic Formula 21 was adjusted to 9 with hydrochloric acid to obtain Comparative Example 29.

[0324] Example 31: The pH value of the basic formula 22 was adjusted to 9 with hydrochloric acid to obtain Example 31.

[0325] Comparative Example 29 and Example 31 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 29 was used as a control, and the growth rate of hexametaphosphate retention in Example 31 was calculated. The results are shown in Table 22.

[0326] Table 22: Growth rate (%) of hexametaphosphate retention in Examples 26-31 and Comparative Example 23

[0327] Comparative Example 23 Example 26 Example 27 Example 28 Example 29 Example 30 Example 31 pH value 5.5 6 6.5 7 8 8.5 9 growth rate of retention 2.84 8.69 28.77 39.01 25.66 17.38 3.21

[0328] Table 22 shows that:

[0329] Within the pH range of 5.5-9, HA-9 can improve the stability of hexametaphosphate, especially between pH 6.5-8.5, where the improvement is more significant.

[0330] Basic recipe 23-24

[0331] Prepare basic formula 23 and basic formula 24 according to Table 23. All data in the table are weight percentages.

[0332] Table 23

[0333]

[0334]

[0335] As can be seen from Table 23:

[0336] The basic formula 23 is a 0.5% sodium hexametaphosphate aqueous solution;

[0337] The basic formulation 24 is a mixed aqueous solution of 0.5% sodium hexametaphosphate and 0.01% HA-9.

[0338] Example 32, Comparative Example 30

[0339] Comparative Example 30: The pH of Basic Formula 23 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 30.

[0340] Example 32: The pH value of the basic formula 24 was adjusted to 7 with hydrochloric acid to obtain Example 32.

[0341] Example 32 and Comparative Example 30 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 30 was used as a control, and the growth rate of hexametaphosphate retention in Example 32 was calculated. The results are shown in Table 24.

[0342] Table 24:

[0343] Example 32 growth rate of retention 42.84％ pH value 7

[0344] As can be seen from Table 24:

[0345] When 0.01% HA-9 was added to a 0.5% sodium hexametaphosphate aqueous solution and the pH was adjusted to 7, the hexametaphosphate retention increased by 42.84%. This means that under the condition of pH adjustment to 7, 0.01% by weight of HA-9 also significantly improved the stability of 0.5% by weight of hexametaphosphate.

[0346] Basic formula 25-26

[0347] Prepare basic formula 25 and basic formula 26 according to Table 25. All data in the table are weight percentages.

[0348] Table 25

[0349] Raw material name Basic formula 25 Basic formula 26 HA-9 / 0.5 Sodium hexametaphosphate 10 10 Deionized water Add to 100% Add to 100%

[0350] As can be seen from Table 25:

[0351] The basic formula 25 is a 10% sodium hexametaphosphate aqueous solution;

[0352] The basic formulation 26 is a mixed aqueous solution of 10% sodium hexametaphosphate and 0.5% HA-9.

[0353] Example 33, Comparative Example 31

[0354] Comparative Example 31: The pH of Basic Formula 25 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 31.

[0355] Example 33: The pH value of the basic formula 26 was adjusted to 7 with hydrochloric acid to obtain Example 33.

[0356] Example 33 and Comparative Example 31 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 31 was used as a control, and the growth rate of hexametaphosphate retention in Example 33 was calculated. The results are shown in Table 26.

[0357] Table 26:

[0358] Example 33 growth rate of retention 31.62％ pH value 7

[0359] As can be seen from Table 26:

[0360] When 0.5% HA-9 was added to a 10% sodium hexametaphosphate aqueous solution and the pH was adjusted to 7, the hexametaphosphate retention increased by 31.62%; that is, under the condition of pH adjustment to 7, 0.5% by weight of HA-9 also significantly improved the stability of 10% by weight of hexametaphosphate.

[0361] Basic formula 27-28

[0362] Prepare basic formula 27 and basic formula 28 according to Table 27. All data in the table are weight percentages.

[0363] Table 27

[0364] Raw material name Basic Recipe 27 Basic formula 28 HA-9 / 0.05 Sodium pyrophosphate 1.0 1.0 Sodium fluoride 0.22 0.22 Deionized water Add to 100% Add to 100%

[0365] As can be seen from Table 27:

[0366] The basic formulation 27 is a mixed aqueous solution of 1.0% sodium pyrophosphate and 0.22% sodium fluoride;

[0367] Basic Formula 28 is based on Basic Formula 27 with the addition of 0.05% HA-9.

[0368] Example 34, Comparative Example 32

[0369] Comparative Example 32: The pH of Basic Formula 27 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 32.

[0370] Example 34: The pH of the basic formula 28 was adjusted to 7 with hydrochloric acid to obtain Example 34.

[0371] Example 34 and Comparative Example 32 were aged at 40°C for 3 months. The weight ratio of pyrophosphate retained in the formulation was measured. Comparative Example 32 was used as a control, and the growth rate of pyrophosphate retention in Example 34 was calculated. The results are shown in Table 28. For ease of comparison, the growth rate data of retention in Example 9 are included in Table 28.

[0372] Table 28:

[0373] Example 9 Example 34 growth rate of retention 32.64％ 40.32％ pH value 7 7

[0374] As can be seen from Table 28:

[0375] When HA-9 was added to a solution containing 1.0% sodium pyrophosphate and 0.22% sodium fluoride, and the pH was adjusted to 7, the growth rate of pyrophosphate retention was 40.32%. That is, under the same pH conditions, the growth rate of retention in Example 34 containing sodium fluoride was better than that in Example 9.

[0376] Basic formula 29-30

[0377] Prepare basic formula 29 and basic formula 30 according to Table 29. All data in the table are weight percentages.

[0378] Table 29

[0379] Raw material name Basic Recipe 29 Basic formula 30 HA-9 / 0.05 Sodium tripolyphosphate 1.0 1.0 Sodium fluoride 0.22 0.22 Deionized water Add to 100% Add to 100%

[0380] As can be seen from Table 29:

[0381] Basic formulation 29 is a mixed aqueous solution containing 1.0% sodium tripolyphosphate and 0.22% sodium fluoride by weight.

[0382] Basic Formula 30 is based on Basic Formula 29 with the addition of 0.05% HA-9 by weight.

[0383] Example 35, Comparative Example 33

[0384] Comparative Example 33: The pH of Basic Formula 29 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 33.

[0385] Example 35: The pH of the basic formula 30 was adjusted to 7 with hydrochloric acid to obtain Example 35.

[0386] Example 35 and Comparative Example 33 were aged at 40°C for 3 months. The weight ratio of tripolyphosphate retained in the formulation was measured. Comparative Example 33 was used as a control, and the growth rate of tripolyphosphate retention in Example 35 was calculated. The results are shown in Table 30. For ease of comparison, the growth rate of retention in Example 20 is also included in Table 30.

[0387] Table 30:

[0388]

[0389]

[0390] As can be seen from Table 30:

[0391] When HA-9 was added at a weight ratio of 0.05% to a solution containing 1.0% sodium tripolyphosphate and 0.22% sodium fluoride, and the pH was adjusted to 7, the growth rate of tripolyphosphate retention was 44.03%; that is, under the same pH conditions, the growth rate of retention in Example 35 containing sodium fluoride was better than that in Example 20.

[0392] Basic formula 31-32

[0393] Prepare basic formula 31 and basic formula 32 according to Table 31. All data in the table are weight percentages.

[0394] Table 31

[0395] Raw material name Basic Recipe 31 Basic formula 32 HA-9 / 0.05 Sodium hexametaphosphate 1.0 1.0 Sodium fluoride 0.22 0.22 Deionized water Add to 100% Add to 100%

[0396] As can be seen from Table 31:

[0397] The basic formulation 31 is a mixed aqueous solution of sodium hexametaphosphate (1.0% by weight) and sodium fluoride (0.22% by weight).

[0398] Basic Formula 32 is based on Basic Formula 31 with the addition of 0.05% HA-9 by weight.

[0399] Example 36, Comparative Example 34

[0400] Comparative Example 34: The pH of the basic formula 31 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 34.

[0401] Example 36: The pH value of the basic formula 32 was adjusted to 7 with hydrochloric acid to obtain Example 36.

[0402] Example 36 and Comparative Example 34 were aged at 40°C for 3 months. The weight ratio of hexametaphosphate retained in the formulation was measured. Comparative Example 34 was used as a control, and the growth rate of hexametaphosphate retention in Example 36 was calculated. The results are shown in Table 32. For ease of comparison, the growth rate of retention in Example 28 is also included in Table 32.

[0403] Table 32:

[0404] Example 28 Example 36 growth rate of retention 39.01％ 47.05％ pH value 7 7

[0405] As can be seen from Table 32:

[0406] When 0.05% HA-9 was added to a mixed aqueous solution containing 1.0% sodium hexametaphosphate and 0.22% sodium fluoride, and the pH was adjusted to 7, the growth rate of hexametaphosphate retention was 47.05%; that is, under the same pH conditions, the growth rate of retention in Example 36 containing sodium fluoride was better than that in Example 28.

[0407] Methods for evaluating the effectiveness of preventing exogenous pigmentation:

[0408] 1) For each set of examples and comparative examples, select ten HAp [hydroxyapatite tablets], soak them in sterile saliva for 3 hours, take them out, rinse them in 10ml of deionized water for 10s, and measure the L value with a colorimeter;

[0409] 2) Take 10 ml of the solution sample from the example or comparative example, immerse the above HAp tablets in the solution for 3 min, remove them, and rinse them in 10 ml of deionized water for 10 s;

[0410] 3) Soak each group of HAP tablets in 15ml of black tea solution for 3 minutes, remove them, rinse them in 10ml of deionized water for 10 seconds, and measure the L value of the HAP tablet surface with a colorimeter.

[0411] 4) Calculate the change in L value before and after each group of HAp tablets, i.e., L 前 -L 后 The average value was calculated, and the smaller the change in the L value, the better the ability to prevent pigmentation.

[0412] The formulations of Comparative Example 1, Example 9, Comparative Example 16, Example 20, Comparative Example 26, and Example 28 were tested for their effectiveness in preventing exogenous pigmentation.

[0413] Comparative Example 1 contained 1% sodium pyrophosphate and the pH of the formulation was adjusted to 7. Example 9 added 0.05% HA-9 to Comparative Example 1.

[0414] Comparative Example 16 contained 1% sodium tripolyphosphate and the pH of the formulation was adjusted to 7. Example 20 added 0.05% HA-9 to Comparative Example 16.

[0415] Comparative Example 26 contained 1% sodium hexametaphosphate and the pH of the formulation was adjusted to 7. Example 28 was based on Comparative Example 26 with the addition of 0.05% HA-9.

[0416] The results are shown in Table 33 below.

[0417] Table 33:

[0418] Comparative Example 1 Example 9 Comparative Example 16 Example 20 Comparative Example 26 Example 28 ΔL 5.67 5.06 5.11 4.53 4.94 4.34

[0419] As can be seen from Table 33:

[0420] Compared to the corresponding comparative example, the example with added HA-9 showed better pigmentation prevention effect.

[0421] Basic formula 33-38

[0422] Prepare the basic formulas 33-38 according to Table 34. All data in the table are weight percentages.

[0423] Table 34:

[0424]

[0425] As can be seen from Table 34:

[0426] The basic formula 33 is a 5% sodium pyrophosphate aqueous solution;

[0427] The basic formulation 34 is a mixed aqueous solution of 5% sodium pyrophosphate and 0.5% HA-9.

[0428] The basic formula 35 is a 5% sodium tripolyphosphate aqueous solution;

[0429] The basic formulation 36 is a mixed aqueous solution of 5% sodium tripolyphosphate and 0.5% HA-9.

[0430] The basic formula 37 is a 5% sodium hexametaphosphate aqueous solution;

[0431] The basic formulation 38 is a mixed aqueous solution of 5% sodium hexametaphosphate and 0.5% HA-9.

[0432] Comparative Examples 35-37, Examples 37-39

[0433] Comparative Example 35: The pH of Basic Formula 33 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 35.

[0434] Example 37: The pH of the basic formula 34 was adjusted to 7 with hydrochloric acid to obtain Example 37.

[0435] Comparative Example 36: The pH of the basic formula 35 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 36.

[0436] Example 38: The pH value of the basic formula 36 was adjusted to 7 with hydrochloric acid to obtain Example 38.

[0437] Comparative Example 37: The pH of Basic Formula 37 was adjusted to 7 with hydrochloric acid to obtain Comparative Example 37.

[0438] Example 39: The pH of the basic formula 38 was adjusted to 7 with hydrochloric acid to obtain Example 39.

[0439] Comparative Examples 35-37 and Examples 37-39 were aged at 40°C for 3 months, and the weight ratio of polyphosphates retained in the formulation was measured. The growth rate of pyrophosphate retention in Example 37 was calculated using Comparative Example 35 as a control; the growth rate of tripolyphosphate retention in Example 38 was calculated using Comparative Example 36 as a control; and the growth rate of pyrophosphate retention in Example 39 was calculated using Comparative Example 37 as a control. The results of the above retention growth rates are shown in Table 35.

[0440] Table 35:

[0441] Example 37 Example 38 Example 39 growth rate of retention 30.33％ 32.97％ 34.59％ pH value 7 7 7

[0442] The formulations of Comparative Examples 35-37 and Examples 37-39 were tested for their effectiveness in preventing exogenous pigmentation. The results are shown in Table 36 below.

[0443] Table 36:

[0444] Comparative Example 35 Example 37 Comparative Example 36 Example 38 Comparative Example 37 Example 39 ΔL 3.54 3.01 3.13 2.66 2.67 2.19

[0445] As can be seen from Table 36:

[0446] Compared to the corresponding comparative example, the example with added hyaluronic acid HA-9 showed better pigmentation prevention effect.

[0447] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is impossible to exhaustively list all embodiments here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. An application of hyaluronic acid in improving the stability of polyphosphates in oral care compositions, characterized in that: The hyaluronic acid comprises a combination of high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, and low molecular weight hyaluronic acid. The high molecular weight hyaluronic acid has a weight-average molecular weight of 1000-2000 kDa; the medium molecular weight hyaluronic acid has a weight-average molecular weight of 200-600 kDa; and the low molecular weight hyaluronic acid has a weight-average molecular weight of ≤10 kDa. The pH value of the oral care composition is 6-9; The polyphosphate is one or a combination of two or more of pyrophosphate, tripolyphosphate or hexametaphosphate; The high molecular weight hyaluronic acid accounts for 10-50% of the total hyaluronic acid, the medium molecular weight hyaluronic acid accounts for 30-50% of the total hyaluronic acid, and the low molecular weight hyaluronic acid accounts for 20-40% of the total hyaluronic acid. The polyphosphate accounts for 0.5-10% by weight in the oral care composition; The hyaluronic acid accounts for 0.005-1% of the mass of the oral care composition.

2. The application according to claim 1, characterized in that: The polyphosphate accounts for 1.0%-5.0% of the weight of the oral care composition.

3. The application according to claim 1, characterized in that: The hyaluronic acid is one or a combination of two or more of the sodium, potassium, and ammonium salts of hyaluronic acid.

4. The application according to claim 1, characterized in that: The hyaluronic acid constitutes 0.01% - 0.5% of the oral care composition by mass.

5. The application according to claim 1, characterized in that: The pH value of the oral care composition is 6.5-8.

5.

6. The application according to claim 1, characterized in that: The oral care composition includes mouthwash or liquid toothpaste.

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