CN108498362A - Prevent and treat the Toll-like receptor agonist mouthwash of canker sore - Google Patents
Prevent and treat the Toll-like receptor agonist mouthwash of canker sore Download PDFInfo
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- CN108498362A CN108498362A CN201810345488.XA CN201810345488A CN108498362A CN 108498362 A CN108498362 A CN 108498362A CN 201810345488 A CN201810345488 A CN 201810345488A CN 108498362 A CN108498362 A CN 108498362A
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- Prior art keywords
- toll
- receptor agonist
- canker sore
- mouthwash
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- 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
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
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- 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
- A61K8/60—Sugars; Derivatives thereof
- A61K8/606—Nucleosides; Nucleotides; Nucleic acids
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- 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
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- 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
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- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention is to prevent and treat the Toll-like receptor agonist mouthwash of canker sore, it is mainly prepared by following raw material medicaments：Trigalloyl lipopeptid, polyinosinic acid, imiquimod, do not methylate oligodeoxynucleotide, chlorhexidine acetate, honey element, moisturizer, Peppermint essential oil, zinc citrate, thymol, water.The Toll-like receptor agonist mouthwash raw material scientific compatibility of the present invention, it is mutually coordinated, have the function of anti-inflammatory, sterilization, Toll-like receptor agonist in raw material adjusts body Effects on local immunological functions, enhance oral mucosa cell proliferation, repair ability, promote canker sore healing, achievees the effect that treating both manifestation and root cause of disease.
Description
Technical field
The invention belongs to oral care techniques fields, and in particular to a kind of Toll sample receptors preventing, treating canker sore
Agonist mouthwash.
Background technology
Canker sore is a kind of common superficial ulcer damage betided on mucous membrane of mouth.With on the inside of the lip in oral cavity,
The mucous membrane of tongue, tongue abdomen, cheek mucous membrane, vestibular ditch, soft palate etc. is common, occur the single or multiple, grain of rice to soya bean size, be in
Round or oval ulcer, surface cover greyish white or yellow pseudomembrane, and ulcer surface is recessed, the red and swollen hyperemia of surrounding mucosa.Irritation is eaten
Object, drug, hormonal readiness change, local trauma, stress and vitamin or microelement deficiencies are responsible for canker sore,
Not by age limit, women is slightly more than male, can occur throughout the year for morbidity.Ulcer has self limiting, can be at 10 days or so certainly
More, if canker sore frequent occurrence or is risen one after another, medically claim " recurrent oral ulceration ".Pain when canker sore is broken out
Acutely, local cusalgia is apparent, and severe patient can also influence to speak, feed, mood etc., and very big inconvenience is caused to daily life.Area
Big canker sores are heavier, more after can there are scars, or even cause ulcer spot tissue defect.
The drug of currently used treatment canker sore has gargle, lozenge, powder, medicine film, immunosuppressor, immune tune
Save agent and reinforcing agent etc..Preceding several remedy,topical's objects have high-timeliness, but easily recur；A few class systemic therapy drugs one afterwards
As treatment ratio more thoroughly, but side effect is larger.If can be prevented before the onset of canker sore, it is many thus to exempt patient
Pain.
Invention content
In order to solve the above technical problem, the present invention provides the Toll-like receptor agonists for preventing, treating canker sore
Mouthwash.
The present invention provides a kind of purposes of Toll-like receptor agonist, are used to prepare and prevent, treat gargling for canker sore
Saliva.
The Toll-like receptor agonist mouthwash of the present invention for preventing, treating canker sore, which forms, includes：1) Toll-like
Receptor stimulating agent is as active constituent；2) pharmaceutically acceptable carrier.
The Toll-like receptor agonist is respectively 2 agonist of Toll-like receptor --- Pam3CSK4, Toll-like receptor 3
Agonist --- polyinosinic acid, 8 agonist of Toll-like receptor --- imiquimod, 9 agonist of Toll-like receptor --- CpG-
ODN。
The present invention is achieved through the following technical solutions：The Toll-like receptor agonist for preventing, treating canker sore is gargled
Saliva, it is mainly prepared by following raw materials in parts by weight number ratio：1.51 × 10-8% of Pam3CSK4, polyinosinic acid
0.01~0.1%, 2.76 × 10-10% of imiquimod, 1.4 × 10-7% of CpG-ODN, chlorhexidine acetate 0.01~0.05%,
Honey element 0.2~0.4%, moisturizer 6.0~8.0%, Peppermint essential oil 0.5~2.0%, zinc citrate 0.02~0.04%, hundred
In phenol 0.04~0.08%, surplus is distilled water.
A kind of Toll-like receptor agonist mouthwash preventing, treating canker sore, it is mainly by following by weight
The raw material of amount number optimal proportion is prepared：1.51 × 10-8% of Pam3CSK4, polyinosinic acid 0.01~0.1%, miaow
Quinoline not 2.76 × 10-10% of spy, 1.4 × 10-7% of CpG-ODN, chlorhexidine acetate 0.01%, honey element 0.2%, moisturizer
6.0%, Peppermint essential oil 2.0%, zinc citrate 0.03%, thymol 0.04%, surplus are distilled water.
As further improvement of these options, the moisturizer is the mixture of sorbierite and glycerine, mixed weight
Than being 5:1.
A kind of preparation method of the Toll-like receptor agonist mouthwash preventing, treating canker sore, by the original
Material is mixed by corresponding weight proportion, is sufficiently stirred after making to be uniformly dissolved, is poured into Pasteur's instantaneous sterilization machine, is heated to 95 DEG C, is maintained
20 seconds time, complete sterilization, the solution by sterilization should promptly be packed into sterilized vial and seal while hot to get
To a kind of Toll-like receptor agonist mouthwash preventing, treating canker sore.
Mouthwash uses after the meal in the present invention, and each mouthwash spues after containing 1 minute in the oral cavity.
The present invention has the following advantages compared with prior art：Mouthwash can clean oral cavity in the present invention, prevent, treat oral cavity
Ulcer, the Toll-like receptor agonist in mouthwash can adjust body Effects on local immunological functions, enhance the growth of oral mucous epithelia
And repair ability, contribute to wound healing, functional is without side-effects, rapid-action, and treatment time is short, makes suitable for promoting
With.
Description of the drawings
Fig. 1 shows the chemical structural formula of Pam3CSK4.
Fig. 2 shows the chemical structural formula of polyinosinic acid.
Fig. 3 shows the chemical structural formula of imiquimod.
Fig. 4 shows the chemical structural formula of CpG-ODN.
Specific implementation mode
The present inventor after extensive and in-depth study, is found that antiviral and immunoloregulation function Toll for the first time
2,3,8,9 agonist of sample receptor has good curative effect to prevention and treatment canker sore.The present inventor is sent out by check experiment
Existing, the preparation being prepared as active constituent by Toll-like receptor agonist can be effectively facilitated the increasing of oral mucous epithelia
It grows and repairs, to promote the healing of ulcer, and effect is preferable.In addition, compared to the drug of other promotion skin wound healings, contain
The facilitation that the drug of Toll-like receptor agonist component heals to mucous membrane is stronger, more effective.On this basis, this is completed
Invention.
In the present invention, mouthwash is prepared using Toll-like receptor agonist.Toll samples receptor for use in the present invention
Agonist is not particularly limited, and can be the Toll-like receptor agonist of any dosage form, such as commercially available injection, powder
Agent, drops etc..Those skilled in the art can select commercially available different Toll-like receptor agonist formulations further as needed
Prepare the mouthwash of the present invention.
The Toll-like receptor agonist dose that can be used for mouthwash of the present invention is not particularly limited, in general, can be safety
A effective amount of Toll-like receptor agonist dose.
In application mouthwash of the present invention, adjustment applied dose can be needed by object.
The present invention is carried out with reference to embodiment explanation is explained in detail.
Embodiment 1
A kind of Toll-like receptor agonist mouthwash preventing, treating canker sore, the weight percent of raw material are：
Pam3CSK4 1.51×10-8%, polyinosinic acid 1.0%, imiquimod 2.76 × 10-10%, CpG-ODN 1.4 × 10-7%, chlorhexidine acetate 0.05%, honey element 0.3%, moisturizer 7.0%, Peppermint essential oil 2.0%, zinc citrate 0.03%, hundred
In phenol 0.06%, surplus is distilled water；The moisturizer is the mixture of sorbierite and glycerine, and mixed weight ratio is 5:1.
Wherein, preparation method is to mix the raw material by corresponding weight proportion, is sufficiently stirred after making to be uniformly dissolved,
Enter Pasteur's instantaneous sterilization machine, be heated to 95 DEG C, maintain 20 seconds time, completes sterilization, it should be promptly by the solution of sterilization
It is packed into sterilized vial and seals while hot and swash to get to a kind of Toll-like receptor preventing, treating canker sore
Dynamic agent mouthwash.
Embodiment 2
A kind of Toll-like receptor agonist mouthwash preventing, treating canker sore, the weight percent of raw material are：
Pam3CSK4 1.51×10-8%, polyinosinic acid 3.0%, imiquimod 2.76 × 10-10%, CpG-ODN 1.4 × 10-7%, chlorhexidine acetate 0.03%, honey element 0.4%, moisturizer 6.0%, Peppermint essential oil 1.0%, zinc citrate 0.04%, hundred
In phenol 0.08%, surplus is distilled water；Remaining content is in the same manner as in Example 1.
Embodiment 3
A kind of Toll-like receptor agonist mouthwash preventing, treating canker sore, the weight percent of raw material are：
Pam3CSK4 1.51×10-8%, polyinosinic acid 1.0%, imiquimod 2.76 × 10-10%, CpG-ODN 1.4 × 10-7%, chlorhexidine acetate 0.01%, honey element 0.2%, moisturizer 6.0%, Peppermint essential oil 2.0%, zinc citrate 0.03%, hundred
In phenol 0.04%, surplus is distilled water；Remaining content is in the same manner as in Example 1.
Effect of drugs verification test
In order to verify the Toll-like receptor agonist mouthwash that 3 gained of embodiment prevents, treats canker sore, at 120
Canker sore patient has carried out contrast test, is randomly divided into control group and experimental group, every group of each 60 people.Control group：Using quality
A concentration of 0.9% physiological saline substitutes mouthwash, and water melon frost is coordinated to treat.Experimental group：Use the pre- of 3 gained of embodiment
Anti-, treatment canker sore Toll-like receptor agonist mouthwash, uses 10~20mL, two cheeks and lip is agitated when gargling every time
Portion makes solution fully be contacted with ulcer spot in oral cavity, contains spat after gargling 1~2 minute every time.Daily 3~5 times, 3 it is postprandial and
It is used before sleep, 3 days as a treatment course.It observes and compares patient's contrafluxion, oedema, pain and ulcer healing after two groups of treatments
Situation.
Efficacy evaluation with reference in December, 2000 China's dentistry can oral mucosal disease Professional Committee the 1st the 3rd time it is complete
It can pass through《Recurrent aphthous ulcer therapeutic evaluation tentative standard》.Recovery from illness：Malaise symptoms completely disappear, and mucosa ulcer disappears
It loses.It is effective：Malaise symptoms are alleviated, and ulcer part disappears.In vain：Malaise symptoms are without alleviation, and ulcer is without reduction.
1 treatment of table
Efficacy analysis：As it can be seen from table 1 preventing, treating the Toll-like of canker sore using 3 gained of the embodiment of the present invention
The cure rate of receptor stimulating agent mouthwash is up to 91.67%, and total effective rate reaches 100%, using pair of other treatment schemes
80% is only reached according to the cure rate of group, comparatively, is increased substantially using the mouthwash curative effect of the present embodiment 3, and cure rate
It is obviously improved.
2 self-induction symptom of table improves situation
In 3 days of observation period, the Toll-like receptor agonist that canker sore is prevented, treated using 3 gained of embodiment is gargled
The patient's self-induction symptom for having up to 95% or more of saliva improves, and uses only 80% or more feeling of other treatment schemes
Symptom improves, it can be seen that the Toll-like receptor agonist mouthwash of canker sore is prevented, treated using 3 gained of embodiment
More remarkable treatment effect.
Clinical tests prove that the present invention in mouthwash have therapeutic effect to canker sore, can rapid recovery oral cavity burst
Pain caused by ulcer and sense of discomfort promote the detumescence of ulcer and the healing as early as possible of ulcer surface, play apparent inhibition, be suitable for
It promotes the use of.
Finally it should be noted that embodiment 3 is the optimal specific implementation mode of the present invention, it is not limited to this
Invention, although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, according to
It so can be with technical scheme described in the above embodiments is modified.All within the spirits and principles of the present invention, made
Any modification, improvement etc., should all be included in the protection scope of the present invention.
Claims (6)
1. preventing, treating the Toll-like receptor agonist saliva of canker sore, it is characterised in that it contains：1) Toll-like receptor 2,
3,8,9 agonists are as active constituent；2) pharmaceutically acceptable carrier.
2. the Toll-like receptor agonist saliva for preventing, treating canker sore, feature exist as described in the appended claim 1
In 2,3,8,9 agonist of Toll-like receptor is respectively trigalloyl lipopeptid, polyinosinic acid, imiquimod, do not methylate widow
Poly- deoxynucleotide.
3. preventing, treating the Toll-like receptor agonist saliva of canker sore as described in the appended claim 1, it is characterised in that it leads
If being prepared by the following raw material matched in parts by weight：Trigalloyl lipopeptid (Pam3CSK4) 1.51 × 10-8%, poly IC
Thuja acid 0.01~0.1%, 2.76 × 10-10% of imiquimod, do not methylate oligodeoxynucleotide (CpG-ODN) 1.4 × 10-
7%, chlorhexidine acetate 0.01~0.05%, honey element 0.2~0.4%, moisturizer 6.0~8.0%, Peppermint essential oil 0.5~
2.0%, zinc citrate 0.02~0.04%, thymol 0.04~0.08%, surplus are distilled water.
4. a kind of Toll-like receptor agonist mouthwash according to claim 1 or 3 preventing, treating canker sore,
It is characterized in that it is mainly made of the raw material of following optimal proportion in parts by weight：1.51 × 10-8% of Pam3CSK4, poly- flesh
Cytidine monophosphate 0.01~0.1%, 2.76 × 10-10% of imiquimod, 1.4 × 10-7% of CpG-ODN, chlorhexidine acetate 0.01%,
Honey element 0.2%, moisturizer 6%, Peppermint essential oil 2.0%, zinc citrate 0.03%, thymol 0.04%, surplus are distilled water.
5. preventing, treating the Toll-like receptor agonist mouthwash of canker sore as described in claim 3 or 4, feature exists
In adjusting body Effects on local immunological functions, enhancing oral mucosa cell proliferation, repair ability promote canker sore healing.The guarantor
Humectant is the mixture of sorbierite and glycerine, and mixed weight ratio is 5:1.
6. prepared by the Toll-like receptor agonist mouthwash according to claim 3 or 4 for preventing, treating canker sore
Method is to mix the raw material by corresponding weight proportion, is sufficiently stirred after making to be uniformly dissolved, pours into Pasteur's instantaneous sterilization machine, add
Heat maintains 20 seconds time to 95 DEG C, completes sterilization, and the solution by sterilization should promptly be packed into sterilized vial simultaneously
It is sealed while hot to get to a kind of Toll-like receptor agonist mouthwash preventing, treating canker sore.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810345488.XA CN108498362A (en) | 2018-04-17 | 2018-04-17 | Prevent and treat the Toll-like receptor agonist mouthwash of canker sore |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201810345488.XA CN108498362A (en) | 2018-04-17 | 2018-04-17 | Prevent and treat the Toll-like receptor agonist mouthwash of canker sore |
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| CN108498362A true CN108498362A (en) | 2018-09-07 |
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| CN201810345488.XA Withdrawn CN108498362A (en) | 2018-04-17 | 2018-04-17 | Prevent and treat the Toll-like receptor agonist mouthwash of canker sore |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1671412A (en) * | 2002-08-15 | 2005-09-21 | 3M创新有限公司 | Immunostimulatory compositions and methods of stimulating an immune response |
| WO2008073174A2 (en) * | 2006-09-08 | 2008-06-19 | The Regents Of The University Of California | Antimicrobial therapy |
| CN101780279A (en) * | 2009-12-22 | 2010-07-21 | 中山大学中山眼科中心 | Application of Toll-link receptor-3 agonist to preparation of medicines for promoting wound healing |
| CN101990435A (en) * | 2008-02-15 | 2011-03-23 | 海米斯费克斯生物制药公司 | Selective agonist of toll-like receptor 3 |
| CN102905726A (en) * | 2010-06-03 | 2013-01-30 | 葛兰素史密丝克莱恩生物有限公司 | Oral vaccine comprising antigen and Toll-like receptor agonist |
| CN104188816A (en) * | 2014-08-11 | 2014-12-10 | 中国人民解放军第四军医大学 | Mouth wash and preparation method thereof |
| CN104606085A (en) * | 2013-11-22 | 2015-05-13 | 中国人民解放军第三军医大学 | Novel efficient antimicrobial chlorhexidine acetate nanoemulsion gargle and preparation method thereof |
-
2018
- 2018-04-17 CN CN201810345488.XA patent/CN108498362A/en not_active Withdrawn
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1671412A (en) * | 2002-08-15 | 2005-09-21 | 3M创新有限公司 | Immunostimulatory compositions and methods of stimulating an immune response |
| WO2008073174A2 (en) * | 2006-09-08 | 2008-06-19 | The Regents Of The University Of California | Antimicrobial therapy |
| CN101990435A (en) * | 2008-02-15 | 2011-03-23 | 海米斯费克斯生物制药公司 | Selective agonist of toll-like receptor 3 |
| CN101780279A (en) * | 2009-12-22 | 2010-07-21 | 中山大学中山眼科中心 | Application of Toll-link receptor-3 agonist to preparation of medicines for promoting wound healing |
| CN102905726A (en) * | 2010-06-03 | 2013-01-30 | 葛兰素史密丝克莱恩生物有限公司 | Oral vaccine comprising antigen and Toll-like receptor agonist |
| CN104606085A (en) * | 2013-11-22 | 2015-05-13 | 中国人民解放军第三军医大学 | Novel efficient antimicrobial chlorhexidine acetate nanoemulsion gargle and preparation method thereof |
| CN104188816A (en) * | 2014-08-11 | 2014-12-10 | 中国人民解放军第四军医大学 | Mouth wash and preparation method thereof |
Non-Patent Citations (3)
| Title |
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| 余元勋等: "《中国疾病信号通路与靶向治疗学》", 31 May 2013, 安徽科学技术出版社 * |
| 王宗厚: "《日用工业品商品与检验》", 31 May 1994, 中国轻工业出版社 * |
| 章崇杰: "《医药免疫学》", 31 August 2009, 四川大学出版社 * |
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