CN103405470A - Application of hyaluronic acid and hyaluronate in preparation of composition for treating and alleviating xerostomia - Google Patents
Application of hyaluronic acid and hyaluronate in preparation of composition for treating and alleviating xerostomia Download PDFInfo
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Abstract
The invention provides an application of hyaluronic acid and hyaluronate in preparation of a composition for treating and alleviating xerostomia and the composition for treating and alleviating xerostomia. As hyaluronic acid and hyaluronate thereof are in double helix columnar structures, and massive hydroxyls exist inside the double helix structures, the hyaluronic acid and hyaluronate thereof have a very good water holding effect, so that the hyaluronic acid and hyaluronate thereof have lasting moisturizing effect on oral cavity. Furthermore, the hyaluronic acid and hyaluronate thereof can promote wound healing and have the effects of healing anabrosis and the like. In addition, the hyaluronic acid and hyaluronate thereof are colorless and tasteless and free from toxicity, belong to synthetic substances in human body, and are easy to be compatible with ions such as sodium, potassium, calcium, zinc, ferrum and silver ions, so that the hyaluronic acid and hyaluronate thereof have the taste which is suitable for being accepted by human body.
Description
Technical field
The invention belongs to medical field, relate in particular to hyaluronic acid and hyaluronate in the application that is used for the treatment of and alleviates the compositions of xerostomia.
Background technology
Normal person's salivation amount of a day is about 1500ml, so that oral mucosa is moistening, does not feel xerostomia.Xerostomia is the caused a kind of symptom of aptyalism in oral cavity.The generation of saliva and secretion are subjected to the impact of whole body, part, the external world and self each factor.The reason of xerostomia is a lot, comprises excited, anxiety, the side effect of radiation exposure, chemotherapy, salivary gland excision, some specific drugs (as diabetes medicament, neuropathy medicine), and preoperative and postoperative 24 hours is drinkable water etc. not.
The xerostomia consequence comprise chew, swallow, parathria, sleep procedure is interrupted, comparatively serious is to cause stomatocace, the dental disorder that comprises dental caries, the candidiasis incidence rate increases, and the Fructus Vitis viniferae pearl infects, and the halitosis of latter's initiation, to the patient, put to no little inconvenience, greatly reduce its quality of life.
In recent years, the xerostomia patient is more and more many, and the prevalence of China's xerostomia has been about 0.29%～0.77%, for the treatment of xerostomia with alleviate and more and more be subject to people's attention.
In order to treat and to alleviate xerostomia, prior art is mainly to adopt the mode of synthetic artificial saliva, if usingd, contains the solution of Carboxymethyl cellulose sodium, sorbitol, potassium chloride, sodium chloride, magnesium chloride etc. as artificial saliva.Though the misery of sufferer has been alleviated in this kind artificial saliva to a certain extent, still, its defect is that mouthfeel is poor, and action time is short.
Summary of the invention
In view of this, the invention provides the application in being used for the treatment of and alleviating the compositions of xerostomia of a kind of hyaluronic acid and hyaluronate, said composition has comfortable taste, the advantage of long action time.
The application is achieved in that
The invention provides the application in being used for the treatment of and alleviating the medicine group of xerostomia of a kind of hyaluronic acid and hyaluronate
Preferably, in embodiments of the present invention, described hyaluronate is hyaluronate sodium, potassium hyaluronate, calcium hyauronate, Curiosin, hyaluronic acid ferrum or hyaluronic acid silver.
In addition, the present invention also provides a kind of compositions that is used for the treatment of and alleviates xerostomia, comprises hyaluronic acid solution and/or hyaluronic acid saline solution.
Preferably, in embodiments of the present invention, described hyaluronate is one or more in hyaluronate sodium, potassium hyaluronate, calcium hyauronate, Curiosin, hyaluronic acid ferrum and hyaluronic acid silver.
Preferably, in embodiments of the present invention, the hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are one or more in 2000kDa～3000kDa, 1000kDa～2000kDa, 500kDa～1000kDa.
Preferably, in embodiments of the present invention, the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 0.1wt%～3wt%.
Preferably, in embodiments of the present invention, hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are 2000kDa～3000kDa, and the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 0.1wt%～1.5wt%.
Preferably, in embodiments of the present invention, hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are 1000kDa～2000kDa, and the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 1.2wt%～1.8wt%.
Preferably, in embodiments of the present invention, hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are 500kDa～1000kDa, and the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 1.5wt%～3wt%.
Preferably, in embodiments of the present invention, also comprise Chinese medicine with the effect of promoting the production of body fluid, promote the cell migration agent, one or more in vitamin, imitative ptyalin, Sunlight chrysanthemum of long handle extract, quinoline promise acetone derivatives, antibacterials, germ killing drugs, digestive enzyme, oral cavity probiotic bacteria, anti-inflammation drugs, xylitol, lactoferrin, lysozyme and immunoglobulin.
The invention provides the application in being used for the treatment of and alleviating the medicine group of xerostomia of a kind of hyaluronic acid and hyaluronate.The Double helix column structure of hyaluronic acid and salt thereof and the great amount of hydroxy group of double-spiral structure inboard make it have very excellent water conservation effect, can realize lasting moistening effect to oral cavity; Hyaluronic acid and salt thereof can promote wound healing, have the effects such as healing ulcer; In addition, hyaluronic acid and salt colorless and odorless thereof, avirulence, belong to synthetic in human body, easily compatible with sodium, potassium, calcium, zinc, ferrum, silver-colored plasma, therefore has the mouthfeel that is suitable for human body acceptance.
The present invention also provides a kind of compositions that is used for the treatment of and alleviates xerostomia, comprises hyaluronic acid solution and/or hyaluronic acid saline solution.In conjunction with the above-mentioned advantage of hyaluronic acid and salt thereof and experimental results show that as can be knownly, compositions provided by the invention has following advantage:
Water conservation effect excellence, can realize lasting moistening effect to oral cavity, reduces patient's medication number of times;
Can promote wound healing, have the effects such as healing ulcer, improve patient's oral environment;
Colorless and odorless, avirulence, belong to synthetic in human body, easily compatible with sodium, potassium, calcium, zinc, ferrum, silver-colored plasma, has the mouthfeel that is suitable for human body acceptance, alleviates the misery of patient's medication.
The specific embodiment
Below will the technical scheme in the embodiment of the present invention be clearly and completely described, obviously, described embodiment is only the present invention's part embodiment, rather than whole embodiment.Based on the embodiment in the present invention, those of ordinary skills, not making under the creative work prerequisite the every other embodiment obtained, belong to the scope of protection of the invention.
The embodiment of the present invention provides a kind of hyaluronic acid and the application of hyaluronate in the compositions for the preparation for the treatment of and alleviation xerostomia.
Hyaluronic acid (hyaluronic acid, HA) is a kind of linear polysaccharide alternately be formed by connecting with glycosidic linkage by β-D-Glucose aldehydic acid and 2-Acetamido-2-deoxy-D-glucose, and it extensively is present in higher mammal and zootic extracellular matrix.Hyaluronic acid is present in extracellular matrix, is the own composition of human body, there is no species specificity; Has excellent biocompatibility, non-immunogenicity.
Hyaluronic acid has following characteristics:
(1) moisture-keeping function
Hyaluronan molecule is locked in the hydrone of its combination in its Double helix column structure, make moisture be difficult for running off, therefore has special water retention, water holding capacity in theory can be up to 500ml/g, can absorb the moisture content of 1000 times of own wts, for 50 times of sodium alginate, 250～300 times of gauze.
(2) repair
Hyaluronic acid is also a kind of important composition in skin, has the function that epidermal tissue repairs.HA has the ability that absorbs large quantity of fluid, and HA can absorb sepage until saturated, expand into gel after absorbing sepage, is formed with the moist environment that is beneficial to wound healing.People show the basic research of wound healing: extracellular matrix plays very important effect in repair in trauma.
Hyaluronic These characteristics is applied to treat for it and alleviates in the compositions of xerostomia provides prerequisite.Hyaluronic acid is applied in above-mentioned composition, can gives the effect of this agents alleviate xerostomia and promotion wound healing, particularly:
(1) alleviate the xerostomia principle: due to the effect of hydrogen bond between monosaccharide on hyaluronic acid straight chain axle, hyaluronan molecule spatially is the screw cylindrical structure of rigidity, the inboard of post is owing to existing a large amount of hydroxyls to produce strongly hydrophilic, thereby the hydrone of its combination is locked in its Double helix column structure firmly, make moisture be difficult for running off, therefore have special water retention, also just because of this, hyaluronic acid is described as " nature moisturizing factor ".
(2) promote the wound healing principle: hyaluronic acid is one of main matrix composition of application on human skin epidermis and corium; its physiological function is to make moisture enter intercellular substance; and with protein bound, form protein gel, and cell is sticked together, the cellular metabolism effect of bringing into normal play; play and keep cell moisture; Cell protection is not subjected to the infringement of pathogen, accelerates to recover skin histology, improves the wound healing regeneration capacity; reduce cicatrix, the effects such as enhancing immunity.And has fabulous biocompatibility.
Hyaluronate also has These characteristics, is applied to be used for the treatment of and alleviates in the compositions of xerostomia also can give this medicine to alleviate xerostomia and to promote the effect of wound healing.This hyaluronate can be hyaluronate sodium, potassium hyaluronate, calcium hyauronate, Curiosin, hyaluronic acid ferrum or hyaluronic acid silver.
Be applied to treat and alleviate hyaluronic acid in the compositions of xerostomia and the molecular weight of salt is preferably 500kDa～3000kDa, more preferably 1000kDa～2000kDa.If the excessive stability of hyaluronic acid and salt thereof that causes of the molecular weight of hyaluronic acid and salt thereof reduces; Too small hyaluronic acid and the curative effect of salt in treatment and alleviation xerostomia compound thereof that reduces same dosage of molecular weight.
Above-mentioned hyaluronic acid and salt thereof can adopt method preparation well known to those skilled in the art, as hyaluronic acid, can adopt the preparations such as tissue extraction method, microbe fermentation method.
As shown in the above, the Double helix column structure of hyaluronic acid and salt thereof and the great amount of hydroxy group of double-spiral structure inboard make it have very excellent water conservation effect, can realize lasting moistening effect to oral cavity; Hyaluronic acid and salt thereof can promote wound healing, have the effects such as healing ulcer; In addition, hyaluronic acid and salt colorless and odorless thereof, avirulence, belong to synthetic in human body, easily compatible with sodium, potassium, calcium, zinc, ferrum, silver-colored plasma, therefore has the mouthfeel that is suitable for human body acceptance.
Accordingly, the embodiment of the present invention also provides a kind of compositions that is used for the treatment of and alleviates xerostomia, and it comprises hyaluronic acid solution and/or hyaluronic acid saline solution.
In view of the above-mentioned advantage of hyaluronic acid and salt thereof, the present embodiment is used it for the preparation treatment and is alleviated in the compositions of xerostomia.Hyaluronate is specifically as follows one or more in hyaluronate sodium, potassium hyaluronate, calcium hyauronate, Curiosin, hyaluronic acid ferrum or hyaluronic acid silver.Solvent in hyaluronic acid solution or hyaluronic acid saline solution is water, is specifically as follows purified water, distilled water or water for injection.
Hyaluronic acid in hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate can be one or more the combination in 2000kDa～3000kDa, 1000kDa～2000kDa, 500kDa～1000kDa.Further, in a preferred embodiment of the present invention, be used for the treatment of and the concentration of alleviating hyaluronic acid solution in the compositions of xerostomia or hyaluronic acid saline solution is 0.1wt%～3wt%.
Further, the concentration of hyaluronic acid solution or hyaluronic acid saline solution can be adjusted according to the molecular weight of hyaluronic acid or hyaluronate, is specifically as follows:
When the hyaluronic acid in hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate were 2000kDa～3000kDa, the concentration of hyaluronic acid solution or hyaluronic acid saline solution was 0.1wt%～1.5wt%.
When the hyaluronic acid in hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate were 1000kDa～2000kDa, the concentration of hyaluronic acid solution or hyaluronic acid saline solution was 1.2wt%～1.8wt%.
When the hyaluronic acid in hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate were 500kDa～1000kDa, the concentration of hyaluronic acid solution or hyaluronic acid saline solution was 1.5wt%～3wt%.
In addition, in the above-mentioned composition that the present embodiment provides, can also include pharmacological component, can be specifically one or more in the composition that promotes salivation, the composition that improves xerostomia, anti-inflammation antibacterial medicinal, the agent of promotion cell migration, vitamin etc., can also be the Chinese medicine (as Radix Puerariae, Rhizoma Zingiberis Recens, Radix Ginseng etc.) with the effect of promoting the production of body fluid, imitative ptyalin, Sunlight chrysanthemum of long handle extract, have the quinoline promise acetone derivatives of promotion salivation activity etc.
In addition, in the above-mentioned composition that the present embodiment provides, can also include the wound face healings such as antibacterials, germ killing drugs, digestive enzyme, oral cavity probiotic bacteria, anti-inflammation drugs, xylitol and promote medicine, and, can play the protein of antimicrobial molecule effect, such as, can be lactoferrin, lysozyme, immunoglobulin etc.
By adding one or more in above-mentioned various component, can utilize the pharmacological property of each component, thereby play the effect of auxiliary treatment.
After adding said components, likely to changing the mouthfeel of former medicine, in order to improve the mouthfeel of medicine, said composition can also include flavouring agent further, as one or more in Oleum menthae, Fructus Citri tangerinae essence, peach flavor, flavoring banana essence, glass essence.
Above-mentioned composition can be spray, aerosol or solution.Be specifically as follows artificial saliva or collutory etc.
The compositions that the present embodiment provides contains hyaluronic acid solution and/or hyaluronic acid saline solution, and it has the following advantages:
Water conservation effect excellence, can realize lasting moistening effect to oral cavity, reduces patient's medication number of times;
Can promote wound healing, have the effects such as healing ulcer, improve patient's oral environment;
Colorless and odorless, avirulence, belong to synthetic in human body, easily compatible with sodium, potassium, calcium, chlorine plasma, has the mouthfeel that is suitable for human body acceptance, alleviates the misery of patient's medication.
In order to make those skilled in the art further understand the present invention, below in conjunction with embodiment, the compositions that is used for the treatment of and alleviates xerostomia provided by the invention is described.Embodiment mono-
Be prepared as follows the compositions of composition:
Hyaluronic acid (molecular weight is 3000kDa) 0.1wt%
Distilled water surplus
Embodiment bis-
Be prepared as follows the compositions of composition:
Hyaluronate sodium (molecular weight is 2000kDa) 1.5wt%
Distilled water surplus
Embodiment tri-
Be prepared as follows the compositions of composition:
Potassium hyaluronate (molecular weight is 1000kDa) 2wt%
Calcium hyauronate (molecular weight is 500kDa) 1wt%
Distilled water surplus
Embodiment tetra-
Be prepared as follows the compositions of composition:
Embodiment five
Be prepared as follows the compositions of composition:
Comparative example one
Be prepared as follows the compositions of composition:
Method for making: get sodium carboxymethyl cellulose and add in 700 ml distilled waters, soaked overnight, after its swelling, sorbitol, sodium chloride, magnesium chloride, potassium chloride, nipalgin are added, stir after molten and add calcium phosphate and sodium radio-phosphate,P-32 solution, adding distil water is to enough, stir evenly rear use 0.01% hydrochloric acid or 0.05% sodium hydroxide and be adjusted to PH=7, bottling, spend flowing steam sterilization 30 minutes with 100.
Use the compositions of embodiment mono-to five and comparative example one to test the patient who suffers from xerostomia
Tested object: choose 42 xerostomia patients, be divided at random 7 groups (every group of 7 people), be denoted as A group, B group, C group, D group, E group, F group.
Method of testing:
The compositions that the sufferer of A group～E group is used respectively embodiment mono-to embodiment five to provide successively, using method is: spray equably or be applied in oral cavity, every day 5 times.
The compositions that the sufferer usage comparison example one of F group provides;
Evaluation index:
(1) oral environment detects
Before detecting patient's medication, medication is after 1 month, the oral environment of medication after 2 months.Oral environment before medication is labeled as 1 grade, perfects crowd's oral environment and is labeled as 5 grades, and intermediate means is divided into 2 grades, 3 grades and 4 grades.The testing result of every group is averaged number of levels.
(2) wound healing test
Before the medication of record patient, after 1 week of medication, the ulcer quantity in the mouth after 2 weeks of medication, the testing result of every group is averaged number.
(3) moistening effect detects
Before adopting Stimulated whole saliva flow measurement to detect patient's medication and the salivary flow after medication, concrete grammar is as follows:
A, after medication, give embedding paraffin 5g on an empty stomach between early, chew 6min, collects total saliva measuring;
B, 2 as a child gave embedding paraffin 5g again, chewed 6min, collected total saliva amount.
(4), mouthfeel detects
Mouthfeel after the medication of record patient, mouthfeel evaluation after 1 week of continuous record patient medication after medication every day, wherein, evaluation result in every group is as the criterion and (thinks the mouthfeel discomfort if in 7 patients of certain group in a day, there are 4 with the mouthfeel evaluation result of most of patients, think comfortable taste for 3, this organizes this day mouthfeel evaluation result is the mouthfeel discomfort), the overall assessment result is as the criterion (in certain group with the more mouthfeel evaluation result of natural law, have 4 estimating result is that mouthfeel is uncomfortable, 3 estimate result is comfortable taste, and overall assessment result is that mouthfeel is uncomfortable).
Test result is listed in table 1 to table 4:
Table 1 oral environment test result
| ? | Before medication | After medication 1 month | After medication 2 months | Result |
| The A group | 1 grade | 4 grades | 5 grades | Sanitary condition improves |
| The B group | 1 grade | 3 grades | 5 grades | Sanitary condition improves |
| The C group | 1 grade | 3 grades | 5 grades | Sanitary condition improves |
| The D group | 1 grade | 4 grades | 5 grades | Sanitary condition improves |
| The E group | 1 grade | 4 grades | 4 grades | Sanitary condition improves |
| The F group | 1 grade | 3 grades | 4 grades | Sanitary condition improves |
Table 2 wound healing test result
| ? | Before medication | After 1 week of medication | After 2 weeks of medication | Result |
| The A group | 4 place's ulcer | 1 place's ulcer | Nothing | Promote the wound healing excellence |
| The B group | 4 place's ulcer | 1 place's ulcer | Nothing | Promote the wound healing excellence |
| The C group | 5 place's ulcer | 2 place's ulcer | Nothing | Promote the wound healing excellence |
| The D group | 3 place's ulcer | Nothing | Nothing | Promote the wound healing excellence |
| The E group | 4 place's ulcer | Nothing | Nothing | Promote that wound healing is good |
| The F group | 4 place's ulcer | 2 place's ulcer | 1 place's ulcer | Promote that wound healing is good |
Table 3 moistening effect test result
| ? | Before medication | After just medication | After medication 6h | Result |
| The A group | 4.3ml | 8.2ml | 6.9ml | Moistening effect is lasting |
| The B group | 4.2ml | 7.9ml | 6ml | Moistening effect is lasting |
| The C group | 4.3ml | 8ml | 6.4ml | Moistening effect is lasting |
| The D group | 4ml | 9.2ml | 7.3ml | Moistening effect is lasting |
| The E group | 4.4ml | 8ml | 6.8ml | Moistening effect is lasting |
| The F group | 4.4ml | 8ml | 5.6ml | Moistening effect is general |
Table 4 sensory test result
| ? | Mouthfeel |
| The A group | Comfortable taste, tasteless |
| The B group | Comfortable taste, tasteless |
| The C group | Comfortable taste, tasteless |
| The D group | Comfortable taste, tasteless |
| The E group | Comfortable taste, tasteless |
| The F group | Salty in the mouth, mouthfeel is not good enough |
As shown in the above, hyaluronic acid and salt thereof are applied to treat and alleviate in the compositions of xerostomia, have lubricated moisturizing, promote the effect of wound healing, be conducive to alleviate xerostomia patient's disease.And with respect to existing similar medicine, the moistening effect of the medicine that contains hyaluronic acid or hyaluronate provided by the invention is lasting, can make the medium-term and long-term lubricating status that is in of patient's mouth, reduces the medication number of times; Tasteless, comfortable taste, the misery of reduction patient medication.
The explanation of above embodiment is just be used to helping to understand method of the present invention and core concept thereof.It should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of the claims in the present invention.
To the above-mentioned explanation of the disclosed embodiments, make professional and technical personnel in the field can realize or use the present invention.Multiple modification to these embodiment will be apparent for those skilled in the art, and General Principle as defined herein can be in the situation that do not break away from the spirit or scope of the present invention, realization in other embodiments.Therefore, the present invention will can not be restricted to these embodiment shown in this article, but will meet the widest scope consistent with principle disclosed herein and features of novelty.
Claims (10)
1. hyaluronic acid and the hyaluronate application in the compositions for the preparation for the treatment of and alleviation xerostomia.
2. application according to claim 1, is characterized in that, described hyaluronate is hyaluronate sodium, potassium hyaluronate, calcium hyauronate, Curiosin, hyaluronic acid ferrum or hyaluronic acid silver.
3. a compositions that is used for the treatment of and alleviates xerostomia, is characterized in that, comprises hyaluronic acid solution and/or hyaluronic acid saline solution.
4. compositions according to claim 3, is characterized in that, described hyaluronate is one or more in hyaluronate sodium, potassium hyaluronate, calcium hyauronate, Curiosin, hyaluronic acid ferrum and hyaluronic acid silver.
5. compositions according to claim 3, it is characterized in that, the hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are one or more in 2000kDa～3000kDa, 1000kDa～2000kDa, 500kDa～1000kDa.
6. compositions according to claim 5, is characterized in that, the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 0.1wt%～3wt%.
7. compositions according to claim 6, it is characterized in that, hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are 2000kDa～3000kDa, and the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 0.1wt%～1.5wt%.
8. compositions according to claim 6, it is characterized in that, hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are 1000kDa～2000kDa, and the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 1.2wt%～1.8wt%.
9. compositions according to claim 6, it is characterized in that, hyaluronic acid in described hyaluronic acid solution or hyaluronic acid saline solution or the molecular weight of hyaluronate are 500kDa～1000kDa, and the concentration of described hyaluronic acid solution or hyaluronic acid saline solution is 1.5wt%～3wt%.
10. the compositions of stating according to claim 3, it is characterized in that, also comprise Chinese medicine with the effect of promoting the production of body fluid, promote the cell migration agent, one or more in vitamin, imitative ptyalin, Sunlight chrysanthemum of long handle extract, quinoline promise acetone derivatives, antibacterials, germ killing drugs, digestive enzyme, oral cavity probiotic bacteria, anti-inflammation drugs, xylitol, lactoferrin, lysozyme and immunoglobulin.
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| CN106176690B (en) * | 2016-08-30 | 2019-10-18 | 华熙生物科技股份有限公司 | Hyaluronic acid oral care film and preparation method and application |
| CN110382193A (en) * | 2017-03-07 | 2019-10-25 | 株式会社真友生物 | The preparation method of hyaluronate film and the hyaluronate film thus prepared |
| CN111374904A (en) * | 2018-12-29 | 2020-07-07 | 好维股份有限公司 | Oral care composition |
| CN111374904B (en) * | 2018-12-29 | 2023-02-28 | 好维股份有限公司 | Oral care composition |
| CN110151594A (en) * | 2019-06-20 | 2019-08-23 | 华熙生物科技股份有限公司 | A kind of oral cavity composition and its application containing Ectoin and hyaluronic acid |
| CN110960497A (en) * | 2019-12-19 | 2020-04-07 | 华熙生物科技股份有限公司 | Hyaluronic acid buccal tablet and preparation method thereof |
| CN110960497B (en) * | 2019-12-19 | 2022-04-15 | 华熙生物科技股份有限公司 | Hyaluronic acid buccal tablet and preparation method thereof |
| CN112007006A (en) * | 2020-08-07 | 2020-12-01 | 山东省药学科学院 | A pharmaceutical composition for treating oral ulcer, and its preparation method |
| CN112007006B (en) * | 2020-08-07 | 2022-12-30 | 山东省药学科学院 | A pharmaceutical composition for treating oral ulcer, and its preparation method |
| CN114133465A (en) * | 2020-09-03 | 2022-03-04 | 山东华熙海御生物医药有限公司 | Preparation method of potassium hyaluronate, obtained product and application |
| WO2023229557A1 (en) * | 2022-05-23 | 2023-11-30 | Ondokuz Mayis Universitesi | Polymer composite film having properties of adhesion and healing on wet surfaces |
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