CN103405470B - Hyaluronic acid and hyaluronate are being used for treating and alleviating the application of the compositions of xerostomia - Google Patents
Hyaluronic acid and hyaluronate are being used for treating and alleviating the application of the compositions of xerostomia Download PDFInfo
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Abstract
The invention provides hyaluronic acid and hyaluronate in preparation for the application treated and alleviate in the compositions of xerostomia with for treating and alleviate the compositions of xerostomia, owing to the great amount of hydroxy group inside the Double helix column structure of hyaluronic acid and salt thereof and double-spiral structure makes it have extremely excellent Water-saving effect, it is possible to oral cavity to be realized lasting moistening effect；And, hyaluronic acid and salt thereof can promote wound healing, have the effects such as healing ulcer；Additionally, hyaluronic acid and salt colorless and odorless, avirulence, belong to synthetic in human body, easily compatible with sodium, potassium, calcium, zinc, ferrum, silver plasma, therefore there is the mouthfeel being suitable to human body acceptance.
Description
Technical field
The invention belongs to medical field, particularly relate to hyaluronic acid and hyaluronate for treat and alleviate oral cavity do
The application of dry compositions.
Background technology
Normal person's salivation amount of a day is about 1500ml, so that oral mucosa moistens and do not feels xerostomia.Xerostomia is
A kind of symptom caused by aptyalism in oral cavity.The generation of saliva and secretion by whole body, locally, extraneous and self each factor
Impact.The reason of xerostomia is a lot, including excited, anxiety, lonizing radiation irradiation, chemotherapy, salivary gland excision, some specific drugs
The side effect of (such as diabetes medicament, neurologic drugs), preoperative and postoperative 24 hours not drinkable water etc..
Xerostomia consequence includes chewing, swallows, parathria, sleep procedure is interrupted, and the most seriously causes oral mucosa
Ulcer, including the dental disorder of dental caries, candidiasis incidence rate increases, and Fructus Vitis viniferae pearl infects, and the halitosis that the latter causes, to patient
Put to no little inconvenience, be substantially reduced its quality of life.
In recent years, xerostomia patient is the most, the prevalence of China's xerostomia be about 0.29%～
0.77%, treatment and alleviation for xerostomia are increasingly subject to people's attention.
In order to treat and alleviate xerostomia, prior art mainly uses the mode of synthesis artificial saliva, as to contain
There is the solution of Carboxymethyl cellulose sodium, sorbitol, potassium chloride, sodium chloride, magnesium chloride etc. as artificial saliva.This kind of artificial saliva
Though alleviating the misery of sufferer to a certain extent, but, having a disadvantage in that mouthfeel is poor, action time is short.
Summary of the invention
In view of this, the present invention provides a kind of hyaluronic acid and hyaluronate for treating and alleviating xerostomia
Application in compositions, said composition has comfortable taste, the advantage of long action time.
The application is achieved in that
The present invention provides a kind of hyaluronic acid and hyaluronate for treating and alleviating in the medicine group of xerostomia
Application
Preferably, in embodiments of the present invention, described hyaluronate is hyaluronate sodium, potassium hyaluronate, hyalomitome
Acid calcium, Curiosin, hyaluronic acid ferrum or hyaluronic acid silver.
Additionally, the present invention also provides for a kind of compositions for treating and alleviate xerostomia, including hyaluronic acid solution
And/or hyaluronate solution.
Preferably, in embodiments of the present invention, described hyaluronate is hyaluronate sodium, potassium hyaluronate, hyalomitome
One or more in acid calcium, Curiosin, hyaluronic acid ferrum and hyaluronic acid silver.
Preferably, in embodiments of the present invention, the hyaluronic acid in described hyaluronic acid solution or hyaluronate solution
Or the molecular weight of hyaluronate be 2000kDa～in 3000kDa, 1000kDa～2000kDa, 500kDa～1000kDa one
Plant or multiple.
Preferably, in embodiments of the present invention, the concentration of described hyaluronic acid solution or hyaluronate solution is
0.1wt%～3wt%.
Preferably, in embodiments of the present invention, the hyaluronic acid in described hyaluronic acid solution or hyaluronate solution
Or the molecular weight of hyaluronate is 2000kDa～3000kDa, described hyaluronic acid solution or the concentration of hyaluronate solution
For 0.1wt%～1.5wt%.
Preferably, in embodiments of the present invention, the hyaluronic acid in described hyaluronic acid solution or hyaluronate solution
Or the molecular weight of hyaluronate is 1000kDa～2000kDa, described hyaluronic acid solution or the concentration of hyaluronate solution
For 1.2wt%～1.8wt%.
Preferably, in embodiments of the present invention, the hyaluronic acid in described hyaluronic acid solution or hyaluronate solution
Or the molecular weight of hyaluronate is 500kDa～1000kDa, described hyaluronic acid solution or the concentration of hyaluronate solution
For 1.5wt%～3wt%.
Preferably, in embodiments of the present invention, also include there is the Chinese medicine of effect of promoting the production of body fluid, promote that cell migration agent, dimension are raw
Element, imitative ptyalin, Sunlight chrysanthemum of long handle extract, quinoline promise acetone derivatives, antibacterials, germ killing drugs, digestive enzyme, oral cavity are prebiotic
One or more in bacterium, anti-inflammation drugs, xylitol, lactoferrin, lysozyme and immunoglobulin.
The present invention provides a kind of hyaluronic acid and hyaluronate for treating and alleviating in the medicine group of xerostomia
Application.Great amount of hydroxy group inside the Double helix column structure of hyaluronic acid and salt thereof and double-spiral structure makes it have extremely
Excellent Water-saving effect, can realize lasting moistening effect to oral cavity；Hyaluronic acid and salt thereof can promote wound healing, tool
There are the effects such as healing ulcer；Additionally, hyaluronic acid and salt colorless and odorless, avirulence, belong to synthetic in human body, easily with
Sodium, potassium, calcium, zinc, ferrum, silver plasma are compatible, therefore have and are suitable to the mouthfeel that human body accepts.
The present invention also provides for a kind of compositions for treating and alleviate xerostomia, including hyaluronic acid solution and/or
Hyaluronate solution.Knowable to hyaluronic acid and the above-mentioned advantage of salt and experiment proof thereof, the combination that the present invention provides
Thing has the advantage that
Water-saving effect is excellent, and oral cavity can realize lasting moistening effect, reduces the times for spraying of patient；
Wound healing can be promoted, there is 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 plasma, have
Have and be suitable to the mouthfeel that human body accepts, alleviate the misery of patient medication.
Detailed description of the invention
Technical scheme in the embodiment of the present invention will be clearly and completely described below, it is clear that described enforcement
Example is only a part of embodiment of the present invention rather than whole embodiments.Based on the embodiment in the present invention, this area is common
The every other embodiment that technical staff is obtained under not making creative work premise, broadly falls into the model of present invention protection
Enclose.
The embodiment of the present invention provides a kind of hyaluronic acid and hyaluronate to be used for treating and alleviating xerostomia in preparation
Compositions in application.
Hyaluronic acid (hyaluronic acid, HA) be by β-D-Glucose aldehydic acid and 2-Acetamido-2-deoxy-D-glucose with
A kind of linear polysaccharide that glycosidic linkage is alternately formed by connecting, it is widely present in higher mammal and zootic extracellular matrix
In.Hyaluronic acid is present in extracellular matrix, is the own composition of human body, does not has species specificity；There is the biofacies of excellence
Capacitive, non-immunogenicity.
Hyaluronic acid has the following characteristics that
(1) moisture-keeping function
The hydrone that hyaluronan molecule is incorporated into is locked in its Double helix column structure, makes moisture not easily run off,
Therefore having special water retention, water holding capacity may be up to 500ml/g in theory, the water of absorbable own wt 1000 times
Part, for 50 times of sodium alginate, 250～300 times of gauze.
(2) repair
Hyaluronic acid is also the important composition of the one in skin, has the function that epidermal tissue repairs.It is big that HA has absorption
The ability of quantity of fluid, HA can absorb sepage until saturated, expand into gel after absorbing sepage, is formed with the wet of beneficially wound healing
Profit environment.The basic research of wound healing is shown by people: extracellular matrix plays very important effect in repair in trauma.
The These characteristics of hyaluronic acid is that it is applied in the compositions for the treatment of and alleviation xerostomia provide premise.Will
Hyaluronic acid is applied in above-mentioned composition, can give this agents alleviate xerostomia and promote the effect of wound healing, specifically
For:
(1) xerostomia principle is alleviated: due to the effect of hydrogen bond between monosaccharide on hyaluronic acid straight chain axle, hyaluronic acid divides
Son spatially screw cylindrical structure in rigidity, the inner side of post produces strongly hydrophilic owing to there is substantial amounts of hydroxyl, thus
The hydrone being incorporated into is locked in its Double helix column structure firmly, makes moisture not easily run off, and it is special therefore to have
Water retention, also just because of this, hyaluronic acid is described as " nature moisturizing factor ".
(2) promoting wound healing principles: hyaluronic acid is one of main matrix composition of application on human skin epidermis and corium, it is raw
Reason function be can make moisture enter intercellular substance, and with protein bound and form protein gel, cell is sticked together, play
Normal cellular metabolism effect, plays holding cell moisture, and protection cell is not encroached on by pathogen, accelerates to recover skin group
Knitting, improve wound healing regeneration capacity, reduce cicatrix, enhancing immunity etc. acts on.And there is fabulous biocompatibility.
Hyaluronate also has These characteristics, is applied to for treating and also alleviating in the compositions of xerostomia
This medicine can be given 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.
The molecular weight being applied to the hyaluronic acid in the compositions for the treatment of and alleviation xerostomia and salt thereof is preferably
500kDa～3000kDa, more preferably 1000kDa～2000kDa.If the molecular weight of hyaluronic acid and salt thereof is excessive, cause
The stability of the acid of bright matter and salt thereof reduces；Molecular weight is too small, and the hyaluronic acid and the salt thereof that reduce same dosage in treatment and alleviate mouth
Curative effect in the drying kinetics compound of chamber.
Above-mentioned hyaluronic acid and salt thereof can use method well known to those skilled in the art to prepare, as hyaluronic acid is permissible
Use the preparation such as tissue isolation, microbe fermentation method.
As shown in the above, a large amount of inside the Double helix column structure of hyaluronic acid and salt thereof and double-spiral structure
Hydroxyl makes it have extremely excellent Water-saving effect, and oral cavity can realize lasting moistening effect；Hyaluronic acid and salt energy thereof
Enough promote wound healing, there is the effects such as healing ulcer；Additionally, hyaluronic acid and salt colorless and odorless, avirulence, belong to human body
Interior synthetic, easily compatible with sodium, potassium, calcium, zinc, ferrum, silver plasma, therefore there is the mouthfeel being suitable to human body acceptance.
Accordingly, the embodiment of the present invention also provides for a kind of compositions for treating and alleviate xerostomia, and it includes
Bright matter acid solution and/or hyaluronate solution.
In view of hyaluronic acid and the above-mentioned advantage of salt thereof, the present embodiment is used it for preparation treatment and alleviates xerostomia
In compositions.Hyaluronate is specifically as follows hyaluronate sodium, potassium hyaluronate, calcium hyauronate, Curiosin, transparent
One or more in matter acid ferrum or hyaluronic acid silver.Solvent in hyaluronic acid solution or hyaluronate solution is water, tool
Body can be purified water, distilled water or water for injection.
Hyaluronic acid or the molecular weight of hyaluronate in hyaluronic acid solution or hyaluronate solution can be
The combination of one or more in 2000kDa～3000kDa, 1000kDa～2000kDa, 500kDa～1000kDa.Further
Ground, in a preferred embodiment of the present invention, for treat and alleviate in the compositions of xerostomia hyaluronic acid solution or
The concentration of hyaluronate solution is 0.1wt%～3wt%.
Further, the concentration of hyaluronic acid solution or hyaluronate solution can be according to hyaluronic acid or hyaluronate
Molecular weight be adjusted, be specifically as follows:
Hyaluronic acid or the molecular weight of hyaluronate in hyaluronic acid solution or hyaluronate solution are 2000kDa
～during 3000kDa, the concentration of hyaluronic acid solution or hyaluronate solution is 0.1wt%～1.5wt%.
Hyaluronic acid or the molecular weight of hyaluronate in hyaluronic acid solution or hyaluronate solution are 1000kDa
～during 2000kDa, the concentration of hyaluronic acid solution or hyaluronate solution is 1.2wt%～1.8wt%.
Hyaluronic acid or the molecular weight of hyaluronate in hyaluronic acid solution or hyaluronate solution are 500kDa
～during 1000kDa, the concentration of hyaluronic acid solution or hyaluronate solution is 1.5wt%～3wt%.
Additionally, the above-mentioned composition of the present embodiment offer can also include pharmacological component, can be specifically to promote
In the composition entering salivation, the composition improving xerostomia, anti-inflammation antibacterial medicinal, promotion cell migration agent, vitamin etc. one
Kind or several, it is also possible to for having the Chinese medicine (such as Radix Puerariae, Rhizoma Zingiberis Recens, Radix Ginseng etc.) of effect of promoting the production of body fluid, imitative ptyalin, Sunlight chrysanthemum of long handle carry
Take thing, there is the quinoline promise acetone derivatives etc. promoting salivation activity.
Additionally, the present embodiment provide above-mentioned composition in can also include antibacterials, germ killing drugs, digestive enzyme,
The wound face healings such as oral cavity probiotic bacteria, anti-inflammation drugs, xylitol promote medicine, and, antimicrobial molecule effect can be played
Protein, such as, can be lactoferrin, lysozyme, immunoglobulin etc..
By adding one or more in above-mentioned various components, it is possible to use the pharmacological property of each component, thus play
The effect of auxiliary treatment.
After adding said components, it is possible to the mouthfeel to the former medicine of change, in order to improve the mouthfeel of medicine, said composition is entered
One step ground can also include flavouring agent, such as in Oleum menthae, Fructus Citri tangerinae essence, peach flavor, flavoring banana essence, glass essence
Plant or several.
Above-mentioned composition can be spray, aerosol or solution.It is specifically as follows artificial saliva or collutory etc..
The compositions that the present embodiment provides contains hyaluronic acid solution and/or hyaluronate solution, and it has following excellent
Point:
Water-saving effect is excellent, and oral cavity can realize lasting moistening effect, reduces the times for spraying of patient；
Wound healing can be promoted, there is 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, have and be suitable to
The mouthfeel that human body accepts, alleviates the misery of patient medication.
In order to make those skilled in the art further appreciate that the present invention, below in conjunction with embodiment, offer of the present invention is used for
The compositions for the treatment of and alleviation xerostomia is described.Embodiment one
Prepare the compositions of following composition:
Hyaluronic acid (molecular weight is 3000kDa) 0.1wt%
Distilled water surplus
Embodiment two
Prepare the compositions of following composition:
Hyaluronate sodium (molecular weight is 2000kDa) 1.5wt%
Distilled water surplus
Embodiment three
Prepare the compositions of following composition:
Potassium hyaluronate (molecular weight is 1000kDa) 2wt%
Calcium hyauronate (molecular weight is 500kDa) 1wt%
Distilled water surplus
Embodiment four
Prepare the compositions of following composition:
Embodiment five
Prepare the compositions of following composition:
Comparative example one
Prepare the compositions of following composition:
Preparation method: take sodium carboxymethyl cellulose and add in 700 milliliters of distilled water, soaked overnight, after it is swelling by sorbitol,
Sodium chloride, magnesium chloride, potassium chloride, nipalgin add, and stir molten rear addition calcium phosphate and sodium radio-phosphate,P-32 solution, add distilled water the most enough,
Regulate to PH=7 with 0.01% hydrochloric acid or 0.05% sodium hydroxide after stirring evenly, bottling, with 100 degree of flowing steam sterilizations 30 minutes.
The patient suffering from xerostomia is tested by the compositions using embodiment one to five and comparative example one
Test object: choose 42 xerostomia patients, be randomly divided into 7 groups (often organizing 7 people), be denoted as A group, B group, C group,
D group, E group, F group.
Method of testing:
The sufferer of A group～E group uses the compositions that embodiment one to embodiment five provides the most respectively, and using method is:
Spray equably or be applied in oral cavity, every day 5 times.
The sufferer of F group uses the compositions that comparative example one provides；
Evaluation index:
(1) oral environment detection
Oral environment before the medication of detection patient, after medication 1 month, after medication 2 months.Oral environment mark before medication
Being designated as 1 grade, perfect crowd's oral environment and be labeled as 5 grades, intermediate means is divided into 2 grades, 3 grades and 4 grades.The testing result often organized takes
Average level number.
(2) wound healing test
Before the medication of record patient, after medication 1 week, the ulcer quantity in mouth after medication 2 weeks, the testing result often organized takes
Mean number.
(3) moistening effect detection
Salivary flow before using Stimulated whole saliva flow measurement detection patient medication and after medication, concrete grammar is such as
Under:
A, early between give to embed paraffin 5g after medication on an empty stomach, chew 6min, collect total saliva amount；
B, 2 the most again give embed paraffin 5g, chew 6min, collect total saliva amount.
(4), mouthfeel detection
Mouthfeel after the medication of record patient, records patient medication mouthfeel evaluation after 1 week after medication every day continuously, its
In, often the evaluation result in group is as the criterion (as having 4 to recognize in 7 patients of certain group in one day with the mouthfeel evaluation result of most of patients
Uncomfortable for mouthfeel, think comfortable taste for 3, this day mouthfeel evaluation result of this group is that mouthfeel is uncomfortable), overall assessment result is with natural law
More mouthfeel evaluation result is as the criterion, and (in certain group, having evaluation result on the 4th is that mouthfeel is uncomfortable, and evaluation result on the 3rd is that mouthfeel is relaxed
Suitable, then 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 | |
| A group | 1 grade | 4 grades | 5 grades | Sanitary condition improves |
| B group | 1 grade | 3 grades | 5 grades | Sanitary condition improves |
| C group | 1 grade | 3 grades | 5 grades | Sanitary condition improves |
| D group | 1 grade | 4 grades | 5 grades | Sanitary condition improves |
| E group | 1 grade | 4 grades | 4 grades | Sanitary condition improves |
| F group | 1 grade | 3 grades | 4 grades | Sanitary condition improves |
Table 2 wound healing test result
| Before medication | After medication 1 week | After medication 2 weeks | Result | |
| A group | Ulcer at 4 | Ulcer at 1 | Nothing | Promote that wound healing is excellent |
| B group | Ulcer at 4 | Ulcer at 1 | Nothing | Promote that wound healing is excellent |
| C group | Ulcer at 5 | Ulcer at 2 | Nothing | Promote that wound healing is excellent |
| D group | Ulcer at 3 | Nothing | Nothing | Promote that wound healing is excellent |
| E group | Ulcer at 4 | Nothing | Nothing | Promote that wound healing is good |
| F group | Ulcer at 4 | Ulcer at 2 | Ulcer at 1 | Promote that wound healing is good |
Table 3 moistening effect test result
| Before medication | After just medication | After medication 6h | Result | |
| A group | 4.3ml | 8.2ml | 6.9ml | Moistening effect is lasting |
| B group | 4.2ml | 7.9ml | 6ml | Moistening effect is lasting |
| C group | 4.3ml | 8ml | 6.4ml | Moistening effect is lasting |
| D group | 4ml | 9.2ml | 7.3ml | Moistening effect is lasting |
| E group | 4.4ml | 8ml | 6.8ml | Moistening effect is lasting |
| F group | 4.4ml | 8ml | 5.6ml | Moistening effect is general |
Table 4 sensory test result
| Mouthfeel | |
| A group | Comfortable taste, tasteless |
| B group | Comfortable taste, tasteless |
| C group | Comfortable taste, tasteless |
| D group | Comfortable taste, tasteless |
| E group | Comfortable taste, tasteless |
| F group | Salty in the mouth, mouthfeel is not good enough |
As shown in the above, hyaluronic acid and salt thereof are applied in the compositions for the treatment of and alleviation xerostomia, tool
There is lubrication moisturizing, promote effect of wound healing, be conducive to alleviating the disease of xerostomia patient.Further, relative to existing
Similar medicine, the moistening effect containing hyaluronic acid or the medicine of hyaluronate that the present invention provides is lasting, can make patient
The medium-term and long-term lubricating status that is in of mouth, reduces times for spraying；Tasteless, comfortable taste, reduces the misery of patient medication.
The explanation of above example is only intended to help to understand method and the core concept thereof of the present invention.It is right to it should be pointed out that,
For those skilled in the art, under the premise without departing from the principles of the invention, it is also possible to the present invention is carried out
Some improvement and modification, these improve and modify in the protection domain also falling into the claims in the present invention.
Described above to the disclosed embodiments, makes professional and technical personnel in the field be capable of or uses the present invention.
Multiple amendment to these embodiments will be apparent from for those skilled in the art, as defined herein
General Principle can realize without departing from the spirit or scope of the present invention in other embodiments.Therefore, the present invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and principles disclosed herein and features of novelty phase one
The widest scope caused.
Claims (1)
1. the compositions being used for treating and alleviate xerostomia, it is characterised in that be made up of following component；
The molecular weight of described Curiosin is 2000KDa.
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| CA2896038C (en) | 2015-07-03 | 2022-08-09 | Glycobiosciences Inc. | Polymer matrix compositions comprising a high concentration of bio-fermented sodium hyaluronate and uses thereof |
| CN105267234A (en) * | 2015-10-29 | 2016-01-27 | 山东省药学科学院 | Composition for relieving xerostomia and preparation method thereof |
| 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 |
| WO2018164358A1 (en) * | 2017-03-07 | 2018-09-13 | (주)진우바이오 | Method for manufacturing hyaluronate film and hyaluronate film manufactured thereby |
| CN111374904B (en) * | 2018-12-29 | 2023-02-28 | 好维股份有限公司 | Oral care composition |
| CN110151594B (en) * | 2019-06-20 | 2022-03-29 | 华熙生物科技股份有限公司 | Oral composition containing ectoin and hyaluronic acid and application 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 |
| 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 |
| CN114133465B (en) * | 2020-09-03 | 2023-03-21 | 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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