CN110870870A - Oral care composition and application thereof in inhibition of gingival bleeding - Google Patents
Oral care composition and application thereof in inhibition of gingival bleeding Download PDFInfo
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- CN110870870A CN110870870A CN201810994972.5A CN201810994972A CN110870870A CN 110870870 A CN110870870 A CN 110870870A CN 201810994972 A CN201810994972 A CN 201810994972A CN 110870870 A CN110870870 A CN 110870870A
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- oral care
- asiaticoside
- care composition
- madecassoside
- degradation product
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- UGTZMIPZNRIWHX-UHFFFAOYSA-K sodium trimetaphosphate Chemical compound [Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 UGTZMIPZNRIWHX-UHFFFAOYSA-K 0.000 description 1
- 235000019832 sodium triphosphate Nutrition 0.000 description 1
- ZUFONQSOSYEWCN-UHFFFAOYSA-M sodium;2-(methylamino)acetate Chemical compound [Na+].CNCC([O-])=O ZUFONQSOSYEWCN-UHFFFAOYSA-M 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7024—Esters of saccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Birds (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an oral care composition, which comprises centella triterpenoid and an orally acceptable carrier; the triterpenoid comprises one or more of asiaticoside, asiaticoside degradation product, madecassoside and madecassoside degradation product. The invention also discloses the application of the asiatic pennywort herb triterpenoid in inhibiting the gingival bleeding; the oral care composition of the invention has four coagulation indexes: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5; can effectively solve the problem of gingival bleeding.
Description
Technical Field
The invention relates to the technical field of oral care, in particular to an oral care composition and application thereof in inhibiting gingival bleeding.
Background
Gingival bleeding is a common oral problem, which is a sign of periodontal problems, often due to chronic inflammation of the gums: after the gum is infected by dental plaque bacteria and stimulated by local tartar, blood vessels expand, tissues are congested, the gum texture becomes brittle, inflammatory reaction of gum soft tissues is caused, and bleeding can occur under the action of external force. If left alone, gingivitis can slowly progress to periodontitis, alveolar bone around the tooth root can gradually break down, the tooth loses support, slowly moves and even falls off, and other diseases can be caused.
The fourth national oral epidemiological survey report shows that the detection rate of gingival bleeding of residents in 35-44 years old in China is up to 87.4%, and compared with that of the residents before 10 years old, the detection rate of gingival bleeding is increased by 10.1%. The health of the oral cavity or the periodontal of the middle-aged people has a plurality of problems, if the periodontal health is not considered, a series of health problems of the whole body are driven, and the fact proves that cardiovascular patients are often found to have oral diseases more or less in clinical diagnosis. Oral disease has become a risk cause of heart disease, streptococci and periodontal pathogens in the oral cavity can cause atherosclerosis and heart attack, periodontal disease caused by bacterial infection is associated with an increased risk of peripheral vascular disease, and severe gum disease increases the risk of stroke and cardiovascular disease. So that bleeding of the gum cannot be ignored.
The existing oral care products mostly adopt a bacteriostatic technology to inhibit the pathogenic factor of dental plaque causing gingival inflammation so as to indirectly exert the effect of reducing gingival bleeding. For example, some products appearing on the market currently, such as Yunnan white drug powder, Oral-B and the like, use the coagulant tranexamic acid in Oral care products to directly exert the effect of relieving gingival bleeding, but the hemostatic agent of the lysine derivative has different proportion of dosage limitation in cosmetic regulations of various countries, and the application of the hemostatic agent has potential thromboembolic risk. Therefore, it would be of great value to find a natural, safe, efficacious alternative oral care composition that would inhibit gingival bleeding.
Centella asiatica (L.) has a long history of application and is widely used in many countries, and mainly contains triterpenes and their glycosides, polyacetylenes, volatile oils, flavonoids, alkaloids, amino acids and other main effective components. The pharmacological actions include inhibiting scar hyperplasia, repairing skin injury, regulating immunity, protecting nerve, resisting ulcer, bacteria, inflammation and pain, and resisting depression and tumor. There is no report on the hemostatic effect.
Disclosure of Invention
The first technical problem to be solved by the present invention is to provide an oral care composition. The oral care composition of the invention has four coagulation indexes: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5; can effectively solve the problem of gingival bleeding.
The second technical problem to be solved by the invention is to provide the application of the asiatic pennywort herb triterpenoid in inhibiting the gingival bleeding.
In order to solve the first technical problem, the invention adopts the following technical scheme:
an oral care composition comprising centella asiatica triterpenoid and an orally acceptable carrier; the triterpenes include one or more of Asiaticoside (Asiaticioside), Asiaticoside degradation product, Madecassoside, and Madecassoside degradation product. The structure of asiaticoside and madecassoside is as follows:
as a further improvement of the technical proposal, the madecassoside degradation product has the following structure:
preferably, the madecassoside degradation product has the following structure:
preferably, the madecassoside degradation product is Madecassic acid (Madecassic acid), of the formula:
as a further improvement of the technical proposal, the asiaticoside degradation product has the following structure:
preferably, the asiaticoside degradation product has the following structure:
preferably, the asiaticoside degradation product is Asiatic acid (Asiatic acid), the structural formula of which is as follows:
preferably, the centella asiatica triterpenoid accounts for 0.01-3% of the composition by mass.
More preferably, the centella asiatica triterpenoid accounts for 0.1-1% of the composition by mass.
As a further improvement of the technical scheme, the asiatic centella triterpenoid at least comprises one of madecassoside and asiaticoside.
Preferably, said centella asiatica triterpenoids comprise at least madecassoside and asiaticoside.
More preferably, the weight ratio of the madecassoside to the asiaticoside is 9:1 to 1: 9.
In order to solve the second technical problem, the invention provides the use of centella asiatica triterpenes for inhibiting gingival bleeding.
Preferably, the asiaticoside triterpenoid comprises one or more of asiaticoside, asiaticoside degradation products, madecassoside and madecassoside degradation products.
Preferably, the centella asiatica triterpenoid is added to toothpaste, gel, mouthwash or tooth powder.
Any range recited herein is intended to include the endpoints and any number between the endpoints and any subrange subsumed therein or defined therein.
The starting materials of the present invention are commercially available, unless otherwise specified, and the equipment used in the present invention may be any equipment conventionally used in the art or may be any equipment known in the art.
Compared with the prior art, the invention has the following beneficial effects:
the oral care composition of the invention has four coagulation indexes: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5; can effectively solve the problem of gingival bleeding.
The application discovers that the centella asiatica triterpenoid has an obvious effect on inhibiting the gingival bleeding for the first time.
Detailed Description
In order to more clearly illustrate the invention, the invention is further described below in connection with preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.
The invention relates to an oral care composition, which comprises centella triterpenoid and an orally acceptable carrier; the triterpenes include one or more of asiaticoside, asiaticoside degradation product, Madecassoside, and Madecassoside. Wherein the structural formula of the madecassoside and the asiaticoside is as follows:
when centella asiatica triterpenes are used, the invention unexpectedly finds that the centella asiatica triterpenes have good hemostatic effect and are superior to the existing hemostatic agents, namely 4-aminomethyl benzoic acid and tranexamic acid.
In certain embodiments of the invention, the madecassoside degradation product has the following structure:
in certain embodiments of the invention, the madecassoside degradation product has the following structure:
in certain embodiments of the invention, the madecassoside degradation product is madecassic acid, having the following structural formula:
in certain embodiments of the invention, the asiaticoside degradation product has the following structure:
in certain embodiments of the invention, the asiaticoside degradation product has the following structure:
in certain embodiments of the invention, the asiaticoside degradation product is asiatic acid, having the following structural formula:
in certain embodiments of the invention, the centella asiatica triterpenoid is present in the composition at a mass ratio of 0.01-3%, or 0.05-2.5%, or 0.05-2%, or 0.05-1.5%, or 0.05-1%, or 0.05-0.5%, or 0.1-3%, or 0.1-2.5%, or 0.1-2%, or 0.1-1.5%, or 0.1-1%, or 0.1-0.5%.
In certain preferred embodiments of the present invention, the centella asiatica triterpenoid is present in the composition in an amount of 0.1-1% by weight.
In certain embodiments of the invention, the centella asiatica triterpenoid comprises at least one of madecassoside, asiaticoside.
In certain preferred embodiments of the present invention, the centella asiatica triterpenoids comprise at least madecassoside and asiaticoside; the weight ratio of the asiaticoside to the madecassoside is 9:1-1:9, or 8:1-1:8, or 7:1-1:7, or 6:1-1:6, or 5:1-1:5, or 4:1-1:4, or 3:1-1:3, or 2:1-1: 2.
In certain embodiments of the present invention, the present invention provides the use of centella asiatica triterpenes for inhibiting gingival bleeding. The application discovers that the centella asiatica triterpenoid has an obvious effect on inhibiting the gingival bleeding for the first time.
In certain embodiments of the present invention, the oral care composition is applied in a toothpaste, gel, mouthwash or tooth powder.
In certain embodiments of the present invention, the oral care composition may further comprise adjuvants such as humectants, flavoring agents, and/or thickening agents.
In certain embodiments of the present invention, the oral care composition may further comprise active ingredients such as antibacterial agents, anticaries agents, anti-sensitivity agents, anticalculus agents, and/or whitening agents.
"humectants" are ingredients that prevent the oral care composition from becoming dehydrated and hardened. Exemplary humectants include, but are not limited to, such as glycerin, propylene glycol, sorbitol, low molecular weight polyethylene glycols, and the like. The humectant is typically present in the oral care composition in an amount of 10 to 80% by mass.
A "thickener" is a substance that increases the viscosity of a solution or liquid/solid mixture, but does not substantially change its properties. The purpose of the thickener is to provide skeleton, flow and stability to the product. Exemplary thickening agents include, but are not limited to, one or more of hydroxyethylcellulose, carboxymethylcellulose and salts thereof (e.g., sodium carboxymethylcellulose), carrageenan (carrageenan), carboxyvinyl polymers, xanthan gum (xanthan g μm), carrageenan, gelatin, pullulan, sodium alginate, and the like. In certain embodiments, the thickening agent comprises one or more of xanthan gum, carrageenan, or sodium carboxymethyl cellulose. The proportion by weight of thickener in the oral care composition is typically from 0.2 to 2%.
The "surfactant" serves the purpose of emulsifying the flavor and foaming in the toothpaste, and to some extent can assist in the sufficient and complete dispersion of the hydroxyapatite-polycarboxyl compound complex. Exemplary surfactants include, but are not limited to, anionic surfactants such as sodium dodecyl sulfate; amphoteric surfactants, such as betaine; amino acid surfactants such as sodium sarcosinate lauryl alcohol and nonionic surfactants such as polyoxyethylene and polyoxypropylene copolymers, polyethylene glycol, and the like. The proportion by weight of the surfactant in the oral care composition is typically from 0.5 to 2.5%.
According to certain embodiments of the present application, active ingredients such as antibacterial agents, anticaries agents, anti-sensitivity agents, anticalculus agents, and/or whitening agents may further be included in the oral care compositions;
by "antibacterial agent" is meant a chemical substance that is capable of maintaining the growth or reproduction of certain microorganisms in an oral care composition below a necessary level over a period of time. Exemplary antimicrobial agents include, but are not limited to: stannous chloride, tetrahydrocurcumin, cetylpyridinium chloride, triclosan, and the like.
"anticaries agent" means a substance having an inhibitory effect on caries, for example, a substance which enhances the anticaries ability of teeth by decreasing the solubility of enamel hydroxyapatite, or a substance which controls plaque, inhibiting bacterial growth. Exemplary anticaries agents include, but are not limited to, phosphorus-containing agents (calcium phosphate, sodium trimetaphosphate, magnesium glycerophosphate, calcium lactate phosphate, sodium caseinate, etc.), or arginine and its derivatives. Preferably, in certain embodiments, the anticaries agent comprises a fluoride ion source.
An "anti-sensitivity agent" refers to a substance that prevents or treats dentinal hypersensitivity by inhibiting nerve impulses or being capable of closing or decreasing the permeability of dentinal tubules. Exemplary anti-sensitivity agents include, but are not limited to: potassium ion sources such as dipotassium glycyrrhizinate, potassium fluoride, potassium nitrate, potassium chloride and the like. Preferably, in certain embodiments, the anti-sensitivity agent comprises a source of potassium ions.
"anticalculus agent" refers to a metal ion complex that acts to combat dental calculus. Exemplary anticalculus agents include, but are not limited to: pyrophosphate, tripolyphosphate, hexametaphosphate or citrate.
The "whitening agent" refers to a substance having a whitening effect on teeth. Exemplary whitening agents include, but are not limited to: peroxide bleaching agent, papain and glucose oxidase.
In the present invention, the effect of inhibiting bleeding is characterized by four items of coagulation.
Four items of blood coagulation
Indices for evaluating the coagulation effect of the raw materials/active ingredients used; the four coagulation phases include: PT, TT, APTT, platelet aggregation rate. The four indexes are also common indexes for detecting whether the blood coagulation function of a patient is normal in a hospital.
First, Prothrombin Time (PT)
The significance of the detection:
PT reflects primarily extrinsic coagulation system conditions. The extrinsic coagulation pathway is regulated primarily by Tissue Factor Pathway Inhibitor (TFPI). TFPI is a glycoprotein present in normal human plasma and platelets and vascular endothelial cells.
Sample preparation
And dissolving the raw material/active substance sample by using normal saline, and diluting according to the proportion of the comparative example/the embodiment to obtain a sample solution to be tested.
Toothpaste samples: mixing 1 part of toothpaste sample with 2 parts of normal saline, and centrifuging at 8000rpm for 20min to obtain supernatant, thereby obtaining a sample to be tested.
The control group was saline.
Then, blood (animal by-product) was taken and mixed with 3.2% sodium citrate at a ratio of 9:1 for anticoagulation. Centrifuging at 3000rpm for 10min, and collecting supernatant to a plastic tube to obtain blood plasma.
Detection method
Adding 0.1ml of experimental plasma into each detection tube, adding 0.05ml of test sample (0.05 ml of physiological saline is used as a negative control group) and mixing; preheating the mixed solution in 37 deg.C water bath for 3min, then preheating 0.2ml thromboplastin at 37 deg.C, then adding the enzyme into the above mixed solution, mixing, and measuring coagulation time with stopwatch; each sample was run in 5 replicates and the mean was calculated.
Thrombin Time (TT)
The significance of the detection:
TT: mainly reflects the time for converting fibrinogen into fibrin, and is an experiment for detecting the functions of blood coagulation, anticoagulation and fibrinolysis systems.
Sample preparation
And dissolving the raw material/active substance sample by using normal saline, and diluting according to the proportion of the comparative example/the embodiment to obtain a sample solution to be tested.
Toothpaste samples: mixing 1 part of toothpaste sample with 2 parts of normal saline, and centrifuging at 8000rpm for 20min to obtain supernatant, thereby obtaining a sample to be tested.
The control group was saline.
Then, blood (animal by-product) was taken and mixed with 3.2% sodium citrate at a ratio of 9:1 for anticoagulation; centrifuging at 3000rpm for 10min, and collecting supernatant to a plastic tube to obtain blood plasma.
Detection method
0.1ml of plasma was added to each tube, and 0.05ml of test sample was mixed in the same procedure (saline as negative control); preheating in 37 deg.C water bath for 3min, adding 0.1ml thrombin, and mixing; measuring the clotting time with a stopwatch; each sample was run in 5 replicates and the mean was calculated.
Activating Partial Thromboplastin Time (APTT)
The significance of the detection:
APTT: mainly reflects the condition of the intrinsic coagulation system and is commonly used for monitoring the dosage of heparin. The increase is seen in reduced levels of plasma factor viii, factor ix and factor XI: such as hemophilia a, hemophilia B, and factor XI deficiency; the decrease is seen in the hypercoagulable state: such as the introduction of procoagulant substances into the blood and increased activity of coagulation factors.
Sample preparation
And dissolving the raw material/active substance sample by using normal saline, and diluting according to the proportion of the comparative example/the embodiment to obtain a sample solution to be tested.
Toothpaste samples: mixing 1 part of toothpaste sample with 2 parts of normal saline, and centrifuging at 8000rpm for 20min to obtain supernatant, thereby obtaining a sample to be tested.
The control group was saline.
Then, blood (animal by-product) was taken and mixed with 3.2% sodium citrate at a ratio of 9:1 for anticoagulation. Centrifuging at 3000rpm for 10min, and collecting supernatant to a plastic tube to obtain blood plasma.
Detection method
0.1ml of plasma was added to each tube, and 0.05ml of test sample was mixed in the same procedure (saline as negative control); preheating in 37 deg.C water bath for 3min, adding activated partial thromboplastin suspension (0.1 ml) preheated at 37 deg.C, and mixing; preheating in 37 deg.C water bath for 5min, adding 0.1ml 0.025mol/L calcium chloride solution preheated at 37 deg.C, and mixing; clotting time was measured with a stopwatch. Each sample was run in 5 replicates and the mean was calculated.
Fourth, platelet aggregation rate
Significance of detection
The platelet aggregation rate is a detection index of platelet function; i.e. the aggregation percentage and rate of platelets; when the platelet aggregation rate is high, the platelets are easy to aggregate and coagulate to form thrombus; when the platelet aggregation rate is low, the platelet aggregation is not easy.
Measurement of the aggregation procedure by optical methods
Requirement of Platelet Rich Plasma (PRP):
when in blood collection, venous blood is mixed with 3.2 percent or 3.8 percent sodium citrate anticoagulant according to the ratio of 9:1, and the collected specimen is detected within 0.5 to 2.5 hours.
Preparation of plasma:
preparing a PRP: centrifuging the anticoagulated sample for 10 minutes at 1000 rpm, and taking the supernatant into a plastic tube.
PPP (platelet-poor plasma) was prepared: the remaining specimen was centrifuged at 3000rpm for 20 minutes and the supernatant was taken in a plastic tube.
The number of platelets in PRP was adjusted to 200,000-300,000/ul.
Sample preparation:
and dissolving the raw material/active substance sample by using normal saline, and diluting according to the proportion of the comparative example/the embodiment to obtain a sample solution to be tested.
Toothpaste samples: mixing 1 part of toothpaste sample with 2 parts of normal saline, and centrifuging at 8000rpm for 20min to obtain supernatant, thereby obtaining a sample to be tested.
The specific operation steps of optical focusing are as follows:
a. adding a magnetic rod with the number of P/N313 into the selected reaction cup, placing the reaction cup in a temperature raising hole, and raising the temperature for 5 minutes;
b. adding 500ul of PRP of a detection specimen into the reaction cup (or adding 250ul of PRP into the reaction cup with the number of P/N312, but adding a rubber pad), and incubating for 5 minutes;
c. adding 500ul of PPP (platelet-poor plasma) of a detection specimen into another reaction cup, and raising the temperature for 5 minutes without adding a magnetic rod;
d. opening the heating cover to place the PRP of the detection sample into the PRP position, and placing the PPP of the detection sample into the PPP position;
e. closing the cover, and adjusting the rotation speed to 1000-;
f. pressing the Set Baselines button automatically sets 100% of the baseline on the computer display screen. The button is released, and the 0% base line is automatically set;
g. the cover is closed immediately after the reagent is added according to the type and methodology of the reagent (before the reagent is added, a dust-free absorbent paper is used for wiping the gun head to ensure that the result is accurate), so that the possible influence of external light is prevented;
h. selecting a Stop test in an aggregate menu when the curve runs for 6-9 minutes until the curve is stable;
i. selecting a set start time and a stop time in an Edit menu, then selecting a pre-edited chanal, then clicking a cursor on a left side line left key in the graph and dragging the line to a position where reagent adding starts, then dragging the cursor on a right side line to a position where a curve starts to be stable, and finally dragging the cursor to the right side line;
j. selecting a cumulative result in an Edit menu, and calculating the aggregation rate and the gradient (the gradient represents the change of the aggregation rate in unit time) after confirming the time;
k. the obtained result can be printed by Save or print in File menu.
The results indicate that: typically identified by percentage aggregation and slope. The calculation of the results is obtained by observing the aggregation curve, the slope representing the aggregation speed per minute.
To summarize: the smaller the PT/TT/APTT index value is, the better the blood coagulation effect is. The larger the index of the platelet aggregation rate is, the better the blood coagulation effect is.
Examples 1 to 5:
an oral care composition is formulated according to the following table.
| Example 1 | Example 2 | Example 3 | Example 4 | Example 5 | |
| Asiaticoside | 0.01 | 0.1 | 1 | 3 | 4 |
| Physiological saline | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent |
The detection result shows that:
| example 1 | Example 2 | Example 3 | Example 4 | Example 5 | |
| PT(s) | 13.9 | 12.77 | 11.27 | 10.11 | 10.19 |
| TT(s) | 41.42 | 39.08 | 36.49 | 33.18 | 33.2 |
| APTT(s) | 24.9 | 25.07 | 23.25 | 20.33 | 20.41 |
| Platelet aggregation rate | 53.8 | 54.6 | 63.8 | 66.05 | 66.17 |
From examples 1-5, it can be seen that the oral care compositions of the present invention achieve four metrics of blood clotting: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5. When the asiaticoside is used in a mass ratio of 1-3%, the effect is better, and the dosage of the asiaticoside exceeds 3%, the asiaticoside does not greatly contribute to four indexes of blood coagulation.
Examples 6 to 10
An oral care composition formulated according to the following formula:
| example 6 | Example 7 | Example 8 | Example 9 | Example 10 | |
| Madecassoside | 0.01 | 0.1 | 1 | 3 | 4 |
| Physiological saline | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent |
The four above oral care compositions were tested for clotting and concluded as follows:
| example 6 | Example 7 | Example 8 | Example 9 | Example 10 | |
| PT(s) | 13.78 | 11.24 | 11.82 | 10.27 | 10.25 |
| TT(s) | 41.05 | 40.23 | 34.01 | 33.79 | 33.82 |
| APTT(s) | 24.43 | 24.05 | 21.37 | 19.41 | 19.5 |
| Platelet aggregation rate | 56.2 | 55.2 | 62.2 | 65.77 | 65.81 |
From examples 6-10, it can be seen that the oral care compositions containing madecassoside set four criteria for clotting: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5. When the asiaticoside is used in a mass ratio of 1-3%, the effect is better, and the dosage of the asiaticoside exceeds 3%, the asiaticoside does not greatly contribute to four indexes of blood coagulation.
Examples 11 to 13
An oral care composition formulated according to the following formula:
| example 11 | Example 12 | Example 13 | |
| Asiatic acid | 0.01 | 0.1 | 1 |
| Physiological saline | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent |
The four above oral care compositions were tested for clotting and concluded as follows:
| example 11 | Example 12 | Example 13 | |
| PT(s) | 14.21 | 12.66 | 11.42 |
| TT(s) | 42.15 | 40.44 | 37.71 |
| APTT(s) | 25.34 | 26.61 | 25.07 |
| Platelet aggregation rate | 54.19 | 56.63 | 59.68 |
From examples 11-13, it can be seen that the oral care compositions containing asiatic acid exhibit four clotting criteria: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5.
Examples 14 to 16
An oral care composition formulated according to the following formula:
| example 14 | Example 15 | Example 16 | |
| Madecassic acid | 0.01 | 0.1 | 1 |
| Physiological saline | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent |
The four above oral care compositions were tested for clotting and concluded as follows:
| example 14 | Example 15 | Example 16 | |
| PT(s) | 14.42 | 12.37 | 11.42 |
| TT(s) | 42.95 | 40.21 | 36.71 |
| APTT(s) | 24.45 | 26.61 | 22.07 |
| Platelet aggregation rate | 55.59 | 56.63 | 59.68 |
From examples 14-16, it can be seen that the oral care compositions containing madecassic acid achieve four criteria for clotting: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5.
Examples 17 to 20
An oral care composition formulated according to the following formula:
| example 17 | Example 18 | Example 19 | Example 20 | |
| Asiaticoside | 0.06 | 0.1 | 0.9 | 0.94 |
| Madecassoside | 0.94 | 0.9 | 0.1 | 0.06 |
| Physiological saline | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent |
The four above oral care compositions were tested for clotting and concluded as follows:
| example 17 | Example 18 | Example 19 | Example 20 | |
| PT(s) | 11.92 | 9.88 | 9.64 | 11.29 |
| TT(s) | 34.98 | 31.73 | 32.06 | 34.45 |
| APTT(s) | 22.21 | 19.79 | 18.81 | 23.21 |
| Platelet aggregation rate | 62.21 | 66.36 | 67.76 | 63.62 |
From examples 17-20, it can be seen that the oral care composition has four indices of blood clotting: prothrombin Time (PT) <12 seconds; thrombin Time (TT) <36 seconds; activated Partial Thromboplastin Time (APTT) <23.5 seconds; the platelet aggregation rate is more than or equal to 62.0, so the blood coagulation effect is better when the oral care composition contains asiaticoside and madecassoside; and has the best blood coagulation effect when the weight ratio of the asiaticoside to the madecassoside is 9:1-1: 9.
Example 21
An oral care composition was formulated as a toothpaste according to the following table formulation and by conventional methods.
The detection result shows that:
| example 20 | |
| PT(s) | 12.35 |
| TT(s) | 37.08 |
| APTT(s) | 24.41 |
| Platelet aggregation rate | 56.29 |
The toothpaste containing the oral care composition of the embodiment has four indexes of blood coagulation: prothrombin Time (PT) is less than or equal to 14.5 seconds; the Thrombin Time (TT) is less than or equal to 42.5 seconds; the Time (APTT) for activating partial thromboplastin is less than or equal to 27.0 seconds; the platelet aggregation rate is more than or equal to 53.5.
Comparative examples 1 to 3
An oral care composition is prepared according to the following formula:
| comparative example 1 | Comparative example 2 | Comparative example 3 | |
| Tranexamic acid | / | 1％ | / |
| 4-aminomethyl-benzoic acid | / | / | 1％ |
| Physiological saline | Adding to 100 percent | Adding to 100 percent | Adding to 100 percent |
The detection result shows that:
when 1 percent by mass of tranexamic acid, 4-aminomethyl benzoic acid or normal saline is used, the four indexes of blood coagulation can not completely achieve the effect required by the invention.
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. Not all embodiments are exhaustive. All obvious changes and modifications which are obvious to the technical scheme of the invention are covered by the protection scope of the invention.
Claims (15)
1. An oral care composition comprising centella asiatica triterpenoid and an orally acceptable carrier; the triterpenoid comprises one or more of asiaticoside, asiaticoside degradation product, madecassoside and madecassoside degradation product.
2. The oral care composition of claim 1, wherein the madecassoside degradation product has the structure:
3. the oral care composition of claim 1, wherein the madecassoside degradation product has the structure:
4. the oral care composition of claim 1, wherein the madecassoside degradation product is madecassic acid, having the following structural formula:
5. the oral care composition of claim 1, wherein the asiaticoside degradation product has the following structure:
6. the oral care composition of claim 1, wherein the asiaticoside degradation product has the following structure:
7. the oral care composition of claim 1, wherein the asiaticoside degradation product is asiatic acid, having the following structural formula:
8. the oral care composition of claim 1, wherein: the centella asiatica triterpenoid accounts for 0.01-3% of the composition by mass.
9. The oral care composition of claim 8, wherein: the centella asiatica triterpenoid accounts for 0.1-1% of the composition by mass.
10. The oral care composition of claim 1, wherein: the asiatic centella triterpenes at least comprise one of madecassoside and asiaticoside.
11. The oral care composition of claim 10, wherein the centella asiatica triterpenoids comprise at least madecassoside and asiaticoside.
12. An oral care composition according to claim 11, wherein the weight ratio of madecassoside to asiaticoside is from 9:1 to 1: 9.
13. Use of centella asiatica triterpenes for inhibiting gingival bleeding is provided.
14. The use according to claim 13: the method is characterized in that: the asiaticoside triterpenes comprise one or more of asiaticoside, asiaticoside degradation products, madecassoside and madecassoside degradation products.
15. The use according to claim 13: the method is characterized in that: the centella asiatica triterpenes is added into toothpaste, gel, mouthwash or tooth powder.
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| WO2023036404A1 (en) * | 2021-09-07 | 2023-03-16 | Symrise Ag | Taste balancing botanical compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111557877A (en) * | 2020-06-24 | 2020-08-21 | 三椒口腔健康股份有限公司 | Toothpaste containing centella extract and preparation method thereof |
| WO2023036404A1 (en) * | 2021-09-07 | 2023-03-16 | Symrise Ag | Taste balancing botanical compounds |
| CN115381729A (en) * | 2022-09-02 | 2022-11-25 | 广州捷创生物科技有限公司 | Toothpaste with effects of whitening skin, removing stains and relieving gingival inflammation and preparation method thereof |
| CN115381729B (en) * | 2022-09-02 | 2023-10-10 | 广东领康日用品有限公司 | Toothpaste with effects of whitening, removing stains and reducing gingivitis and preparation method thereof |
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