CN109908205A - A kind of drug prevented or treat mouth disease - Google Patents
A kind of drug prevented or treat mouth disease Download PDFInfo
- Publication number
- CN109908205A CN109908205A CN201910167575.5A CN201910167575A CN109908205A CN 109908205 A CN109908205 A CN 109908205A CN 201910167575 A CN201910167575 A CN 201910167575A CN 109908205 A CN109908205 A CN 109908205A
- Authority
- CN
- China
- Prior art keywords
- drug
- parts
- mouth disease
- prevention
- oral cavity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention discloses a kind of prevention or the drugs for the treatment of mouth disease, the drug is using gelfoam, rhizoma cibotii hair or chitosan as carrier, using caryophyllus oil, iodoform, calcium hydroxide, peru balsam as effective component, and suitable local anaesthetics composition is added, wherein, the local anaesthetics is lidocaine, totokaine, loxoprofen one of which.With anti-inflammatory, analgesic, disinfection, anti-corrosion, hemostasis, myogenic and prevent the multiple pharmacological effects such as secondary infection, promotion paradenlal tissue regeneration.And medication is convenient, removal is easy, permeability is preferable, it can pain at reduction of patient oral cavity disease damage rapidly, double infection can be prevented by effectivelying prevent environmental liquids to enter cavity its barrier action, and temperature at disease damage is reduced, the dysfunctions such as the local red and swollen heat pain of mucous membrane are eliminated rapidly, are conducive to the reparation of mucous membrane of mouth.
Description
Technical field
The invention belongs to the drugs of field of medical technology, and in particular to a kind of drug prevented or treat mouth disease.
Background technique
Oral hygiene is the component part of healthy living, is the important symbol of progress of social civilization.With oral health
Theory is changed into social life theory, is continuously increased to focusing on for oral health, also gets over to the prevention and treatment of mouth disease
Come more important.Oral cavity is a complicated intact ecocystem, is food into gastral important channel, and be partial digested
The place of liquid secretion, temperature, humidity and the swill for being suitable in oral cavity provide advantageous ring for the growth and breeding of microorganism
The suitable environment of border and condition, even more microbial colonisation and growth can lead to the generation of a variety of diseases.Under normal circumstances flora it
Between mutually restrict, be in equilibrium state, when some field of Maxillary region, some position are by certain damage, intraoral mucous membrane,
Intrusion, the flora imbalance that bacterium can all be incurred in gap, gum, oral pocket, alveolar bone and jawbone etc., cause various inflammation
Disease.There is Multiple space infection, while inflammatory cell infiltration once adjacent gap can also be spread to by infecting in gap, whole body fever,
Local red and swollen heat pain dysfunction, infection of parapharyngeal space and mouth bottom infection of sublingual space can cause expiratory dyspnea even to be suffocated.
It is raw that potassium ion, serotonin, acetylcholine, bradykinin, histamine in extracellular fluid etc. is released into when histocyte inflammation or damage
Active substances can cause pain or hyperalgia.Various inflammation can all generate different degrees of pain, inflammatory pain be by
Pain caused by various biologies (bacterium, fungi, virus etc.), physics, chemistry or immunogenicity inflammation.
Pain is often a cardinal symptom of mouth disease, the World Health Organization pain will be classified as after body temperature, breathing,
Pain is defined as " due to the fact that or potential tissue damage by the 5th vital signs after pulse, blood pressure, international pain association
The caused unhappy feeling of wound and emotional experience ".The stress reaction of pain makes body be in a kind of hypercoagulative state, each to patient
Aspect brings adverse effect, such as: pain can cause stomodaeal nervous system to be overexcited, catecholamine, corticotropin
Secretion increases, and cortisol, Aldosterone Secretion are also increase accordingly；Heart shows increased heart rate, the heart under the action of catecholamine
Convergent force is reinforced, and heart output rating increases, and peripheral blood vessel is shunk, and body circulation resistance increases, and blood pressure increases；Pain and entire body
State is closely related, studies have shown that many symptoms can all aggravate when pain is not controlled, such as tired, anorexia, constipation and nausea；
Meanwhile state can also have an impact spirit of the pain to patient at heart: acute severe pain can cause to be overexcited, and patient is irritated
Uneasiness, long-time chronic ache can lead to central nervous system and depressive state are presented, and may occur in which depressed, apathy, sternly
Severe one can produce introgression；Pain also generates psychological impact, sense and appraxia sense such as out of control.Have an effect on the handling ability and ginseng of people
Add recreation pastime ability.The cognitive process of ache influence people, such as it is absent minded.
Mucous membrane of mouth is the position for being easier to be damaged by extraneous harmful substance or mechanical force in human body mucous layer, and the portion
The disease incidence of position maintains always higher level, and what is clinically more often occurred has recurrent oral ulceration, oral inflammation (side
Edge oulitis, periodontitis) stomatitis traumatica (generally being caused by artificial tooth or correction with tooth set in the majority) etc..Such Disease Clinical symptom
With local swelling, bleeding, pain, Telatrophy etc., serious person festers in oral cavity, can not normal diet, to the daily life of patient
Work is made troubles.
Mouth disease is to endanger one of common disease of human health, currently, drug therapy is mostly whole body and local application,
Systemic therapy medication is comparatively laborious, and dosage is larger, there is adverse reaction, some drugs are after liver " first pass effect ", only very
Low dose keeps complete pharmaceutical activity, and the concentration that drug reaches part is very low.Oral mucosa adherency administration is a kind of novel
Administration route makes drug absorbed through oral mucosa, into the circulatory system, the enzyme of gastrointestinal tract is avoided to be metabolized and acid degradation and liver
First-pass effect.Oral mucosal delivery device has as the characteristics of local treatment:
1, release drug can be positioned in oral cavity partial, improves local drug concentration rapidly, plays quick-acting effects.
2, the bioadhesive of preparation increases preparation in the residence time in oral cavity, extends the action time of drug, can
Play the effect of sustained release.
3, local application reduces internal drug total amount and avoids simultaneously to reduce the generation of systemic toxic side effect
The liver first-pass effect of oral administration.
4, easy to use, patient is easy to receive.
Summary of the invention
In order to preferably treat mouth disease, the object of the present invention is to provide a kind of new treatment mouth diseases
Drug, the drug treatment regimen is wide, to toothache, bleeding gums, oral inflammation, canker sore and all kinds of mouth diseases of mouth infection
Etc. all having preferable therapeutic effect.
In order to realize that above-mentioned task, the present invention take following technical solution:
A kind of drug prevented or treat mouth disease, which is characterized in that the drug is poly- with gelfoam, rhizoma cibotii hair or shell
Sugar is used as carrier, using caryophyllus oil, iodoform, calcium hydroxide, peru balsam as effective component, and suitable local anaesthetics group is added
At, wherein the local anaesthetics is lidocaine, totokaine, loxoprofen one of which.
According to the present invention, the drug obtained is made of following raw materials according and its dosage:
Rhizoma cibotii hair: 8.5 parts, lidocaine: 0.01 part, caryophyllus oil: 4.25 parts, iodoform: 4.25 parts, calcium hydroxide: 2 parts,
Peru balsam: 80 parts.Or
The drug obtained is made of following raw materials according and its dosage:
Gelfoam: 8.5 parts, totokaine: 0.01 part, caryophyllus oil: 4.25 parts, iodoform: 4.25 parts, calcium hydroxide: 2 parts,
Peru balsam: 80 parts.Or
The drug obtained is made of following raw materials according and its dosage:
Chitosan: 8.5 parts, loxoprofen: 0.01 part, caryophyllus oil: 4.25 parts, iodoform: 4.25 parts, calcium hydroxide: 2 parts,
Peru balsam: 80 parts.
Further, the dosage form selection toothpaste of the drug, dripping pill, mouthwass, oral cavity spray liquid, oral cavity, which are used, coagulates
One of glue, oral cavity ointment, oral cavity patch, oral cavity cotton balls, medical grade silicon rubber, oral cavity dressing and chewing gum.
Prevention of the invention or the drug for treating mouth disease have following technology effect compared with traditional oral administration
Fruit:
(1) using mucous membrane of mouth adherency administration, there is anti-inflammatory, analgesic, disinfection, anti-corrosion, hemostasis, myogenic and prevent secondary sense
Dye promotes the multiple pharmacological effects such as paradenlal tissue regeneration,
(2) medication is convenient, and removal is easy, and permeability is preferable, pain at the disease damage of reduction of patient oral cavity, patient can be easier to rapidly
Receive；
(3) double infection can be prevented by effectivelying prevent environmental liquids to enter cavity its barrier action, and drop temperature at disease damage
It is low, the dysfunctions such as the local red and swollen heat pain of mucous membrane are eliminated rapidly, are conducive to the reparation of mucous membrane of mouth.
Specific embodiment
Applicant, can be rapid the study found that drug for preventing or treating mouth disease, increases a small amount of local anaesthetics
Pain at the disease damage of reduction of patient oral cavity reduces temperature at disease damage, eliminates the dysfunctions such as the local red and swollen heat pain of mucous membrane rapidly,
Make patient comfort.
The present embodiment provides a kind of drug prevented or treat mouth disease, and the drug is with gelfoam, rhizoma cibotii hair or shell
Glycan is as carrier, using caryophyllus oil, iodoform, calcium hydroxide, peru balsam as effective component, and suitable local anaesthetics group is added
At, wherein the local anaesthetics is lidocaine, totokaine, loxoprofen one of which.
Eugenol is the main component of caryophyllus oil, has the effects that sterilization, anti-inflammatory, can obviously inhibit Candida albicans etc. more
Kind pathogenic bacteria；Eugenol can block the nerve endings mediator transmitting of surface of a wound exposure simultaneously, inhibit peroxidase activity, reduce inflammation
Medium generates, antipyretic-antalgic；Local anaesthetics lidocaine can alleviate rapidly pain at disease damage, reduce temperature at disease damage, disappear rapidly
The dysfunctions such as the local red and swollen heat pain except mucous membrane, make patient comfort.Caryophyllus oil have it is good fat-soluble, penetrate readily through
Biofilm structure, Penetration enhancing effect is strong, rapid-action, and adverse reaction is small, is good natural permeation enhancers.Calcium hydroxide has height
Anaerobe resistant effect is imitated, the structure of bacteria cell wall and protein can be destroyed, moreover it is possible to the lipoid of hydrolytic bacteria lipopolysaccharides, in change
The biological characteristics of toxin, to hinder film transporting mechanism.Calcium hydroxide can neutralize inflammation production as strong alkaline substance simultaneously
Raw various acidic materials inhibit acid phosphatase, moreover it is possible to inflammatory factor such as tumor necrosis factor and Interleukin -1β be made to lose work
Property, help to mitigate inflammatory reaction degree, relieve pain and swelling acute attack.Iodoform encounters surface of a wound exudate or certain bacteriums
It can release free iodide ion when product, there is long-acting bactericidal effect, it is non-stimulated to organizing, diffusate can be absorbed, the surface of a wound is reduced
Exudation makes the surface of a wound keep drying, and promotes granulation tissue growth, promotes the advantages that wound organization healing.Iodoform and calcium hydroxide
It combines, the two has good synergistic effect, the advantages of combining calcium hydroxide and iodoform, plays its convergence, anti-corrosion and collaboration
Antibacterial action.Peru balsam is a kind of natural perfume material, has a variety of characteristics for being conducive to oral soft tissue, and main component is
Benzoic acid methyl esters has excellent infiltration, hemostasis and bactericidal property.
The drug of the prevention or treatment mouth disease, dosage form selection toothpaste, dripping pill, mouthwass, oral cavity spray
Spray film, mouth gels, oral cavity ointment, oral cavity patch, oral cavity cotton balls, medical grade silicon rubber, oral cavity dressing and mouth are fragrant
One of sugar.
It is the specific embodiment that inventor provides below.
Embodiment 1:
The present embodiment provides a kind of drug prevented or treat mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) rhizoma cibotii hair is taken, clean dry simultaneously sieves with 100 mesh sieve spare；
2) caryophyllus oil, calcium hydroxide, iodoform, peru balsam and lidocaine mixing are taken, is stirred at room temperature uniformly, obtains
Mixed solution；
Rhizoma cibotii hair obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Rhizoma cibotii hair in the present embodiment, barrier action can prevent double infection, avoid the generation of alveolus inflammation after extraction.
Due to including viscous fiber, it is easy to be attached on tooth socket bottom after being put into tooth socket.After wound healing, moves and make in tongue
It is progressively disengaged under.Without doctor's otherwise processed, wound heals quickly.
Embodiment 2:
The present embodiment provides a kind of drug prevented or treat mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) gelfoam is taken, crush and is sieved with 100 mesh sieve is spare；
2) caryophyllus oil, calcium hydroxide, iodoform, peru balsam and totokaine mixing are taken, is stirred at room temperature uniformly, is mixed
Close solution；
Gelfoam powder obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Gelfoam in the present embodiment is a kind of protein sponge with hemostatic function that can be absorbed and be implanted into,
With good biocompatibility and degradability, factor Ⅹ is released after can promote platelet destruction, promotes clot,
To favorably stop blooding.Gelfoam can form the envelope of protective in conjunction with the histone of oral mucosal surface, thus
Avoid pain caused by the various stimulations of outer bound pair mucous membrane table blood.While as pharmaceutical carrier, the surface of a wound can be clogged, easily
It absorbs, it may not be necessary to take out.
Embodiment 3:
The present embodiment provides a kind of drug prevented or treat mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) chitosan is taken, crush and is sieved with 100 mesh sieve is spare；
2) caryophyllus oil, calcium hydroxide, iodoform, peru balsam and loxoprofen mixing are taken, is stirred at room temperature uniformly, obtains
Mixed solution；
3) chitosan obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Chitosan in the present embodiment has good degradability and cell adhesion and biocompatibility, and without immune
It is originality, nontoxic, it is good pharmaceutical carrier.It has been investigated that chitosan has anti-inflammatory, hemostasis, promotes the pharmacology such as organization healing
Effect, and in the attachment time of mucous membrane of mouth up to 4 days or more.
The drug of prevention or treatment mouth disease that above-described embodiment 1,2 or 3 obtains, is adhered to using mucous membrane of mouth to prescription
Formula, drug have barrier action between mucosa and oral cavity, can be full of cavity according to the shape at filling position, be close to the surface of a wound,
Uniform support and compressing are provided, dead space is not stayed, can be reduced stimulation of the oral secretion to mucous membrane of mouth, effectively prevent extraneous liquid
Body, which enters cavity its barrier action, can prevent double infection, and reduce temperature at disease damage, and the part for eliminating mucous membrane rapidly is red and swollen
The dysfunctions such as hot pain.Compared to spray and powder etc., action time is longer, local absorption better effect, and it is glutinous to be conducive to oral cavity
The reparation of film.
Lidocaine is not added by comparative experiments example 1:()
This experiment provides a kind of drug prevented or treat mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) rhizoma cibotii hair is taken, crush and is sieved with 100 mesh sieve is spare；
2) lidocaine, calcium hydroxide, iodoform and peru balsam mixing are taken, is stirred at room temperature uniformly, obtains mixing molten
Liquid；
Rhizoma cibotii hair obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Caryophyllus oil is not added by comparative experiments example 2:()
This experiment provides a kind of drug prevented or treat mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) rhizoma cibotii hair is taken, crush and is sieved with 100 mesh sieve is spare；
2) calcium hydroxide, iodoform, peru balsam and lidocaine mixing are taken, is stirred at room temperature uniformly, obtains mixing molten
Liquid；
Rhizoma cibotii hair obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Iodoform is not added by comparative experiments example 3:()
This experiment provides a kind of for preventing or treating the drug of mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) rhizoma cibotii hair is taken, crush and is sieved with 100 mesh sieve is spare；
2) caryophyllus oil, calcium hydroxide, peru balsam and lidocaine mixing are taken, is stirred at room temperature uniformly, is mixed
Solution；
3) rhizoma cibotii hair obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Calcium hydroxide is not added by comparative experiments example 4:()
This experiment provides a kind of for preventing or treating the drug of mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) rhizoma cibotii hair is taken, crush and is sieved with 100 mesh sieve is spare；
2) caryophyllus oil, iodoform, peru balsam and lidocaine mixing are taken, is stirred at room temperature uniformly, obtains mixed solution；
3) rhizoma cibotii hair obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Peru balsam is not added by comparative experiments example 5:()
This experiment provides a kind of for preventing or treating the drug of mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
1) rhizoma cibotii hair is taken, crush and is sieved with 100 mesh sieve is spare；
2) caryophyllus oil, calcium hydroxide, iodoform and lidocaine mixing are taken, is stirred at room temperature uniformly, obtains mixed solution；
3) rhizoma cibotii hair obtained by step 1) is immersed in the mixed solution of step 2), make its complete wetting to get.
Comparative experiments example 6:(is using hospital gauze as pharmaceutical carrier)
This experiment provides a kind of for preventing or treating the drug of mouth disease, is formulated by following components dosage:
The process for preparing medicine is:
Caryophyllus oil, calcium hydroxide, iodoform and lidocaine mixing are taken, is stirred at room temperature uniformly, obtains mixed solution i.e.
?.
In use, being placed in patient oral cavity patient part by drug coat on hospital gauze.
Above-mentioned, although specific embodiments of the present invention have been described, not to the limit of the scope of the present invention
System, those skilled in the art should understand that, based on the technical solutions of the present invention, those skilled in the art are to the present invention
The various additions or replacement made, all belong to the scope of protection of the present invention.
It is serial drug effect of the inventor to the prevention of above-described embodiment 1,2,3 or the drug progress for treating mouth disease below
Learn experiment:
One, emergency toxicology is tested
The prevention of above-described embodiment 1,2,3 or the drug for treating mouth disease are mucous membrane of mouth adherency administrations, do not do oral
Administration to inquire into the toxic reaction that the possibility of this preparation occurs, therefore uses dressing for skin to be administered.Maximal tolerance dose (MTD) experiment:
Preliminary experiment proves that test medicine toxicity is lower, does not measure LD50, maximal tolerance dose experiment can be done.
By weight (20 ± 2) g small white mouse 20, half male and half female.Before on-test, small white mouse trunk back is subtracted or shaved
The coat in quasi- contamination region, when unhairing, answer extreme care, not damage skin in order to avoid cutaneous permeability.With embodiment 1,
2, the drug of 3 prevention or treatment mouth disease applies surface product and accounts for about the 10% of Mice surface area.Using maximum dosage-feeding
Method, test group disposably give maximum pharmaceutical formulation 5g/kg, by test medicine (the i.e. prevention of embodiment 1,2,3 or treatment mouth
The drug of chamber disease) even application in small white mouse skin of back chemical contaminated zone, then covers with thin film, and non-stimulated adhesive plaster is solid
It is fixed, it prevents animal from licking, administration time 4 hours, is observed continuously 14 days.Control group gives hospital gauze.Before first administration, administration
After a week, small white mouse weight, reaction and death condition after record small white mouse administration are weighed after the test.It is right after the test
All tested small white mouses carry out dissect.
Test result: small white mouse is without apparent toxic reaction, and behavioral activity, the state of mind, appearance, stool and urine etc. is
No abnormality seen.Small white mouse group weight is administered during test not occur significantly sexually revising (P > 0.05) compared with the control group, weight becomes
Change situation and is shown in Table 1.After small white mouse dissection will be tested, the heart, liver, spleen, lung, kidney, adrenal gland, seminal vesicle, prostate, testis are visually observed
Ball, ovary, uterus and thoracic cavity, abdominal cavity and each internal organs are no abnormal.
Table 1: mouse weight situation of change (N=5)
Two, mucous membrane of mouth toxicity and irritation test
20 Wistar rat lower lips are seamed into a blind bag, are divided into 2 groups according to gender, using maximum dosage-feeding method (5g/
Kg), embodiment 1,2,3 is formulated in the infusion of medicine bag of prevention or treatment mouth disease obtained, and it is glutinous to smear its lower gum
Film at least contacts 4 hours (such as test medicine leak out, then be averagely administered multiple times in 4h), observe tested Wistar rat to
The variation of systemic conditions and local mucous membrane for 24 hours, then puts to death part Wistar rat after medicine, takes out oral cavity partial mucous membrane, observation
Whether there is or not the variations such as hyperemia, oedema for mucous membrane, and make histopathological examination.It retains Wistar rat and observes and records day by day entirely in part
Overall health of patients was to the 7th day, then put to death, check mucous membrane substantially and pathological change.As a result: two groups of Wistar rat mucous membranes are complete,
Have no pathological change.
Three, recurrent oral ulceration is tested
40 SD female rats (190 ± 10) g establish canker sore in SD rat or so cheek mucous membrane using chemical burns method
(2% yellow Jackets anaesthetize SD rat to model, the use of bore are Pasteur's pipe absorption saturated carbon that cotton is plugged in 5mm and nozzle
Sour hydrogen sodium solution, Pasteur's nozzle is affixed on the buccal mucosa of SD rat, duration 60s.Cheek mucous membrane at left and right sides of SD rat
Do same treatment.Modeling visually observes after 24 hours, and SD rat mucous membrane of mouth forms the ulcer of a diameter about 5mm.Ulcer
There is the covering of yellow-white pseudomembrane on concavity, surface, around has bleeding and with congestion and edema.HE dyes visible mucosal epithelium and falls off,
Lamina propria has inflammatory cell infiltration.Show modeling success).Left side ulcer surface applies glycerol, is glycerol control group, and right side ulcer surface applies
The prevention of embodiment 1,2 or 3 or treatment mouth disease drug are experimental group, are administered three times a day, administration mode is 1mL tylostyle
Pipe pushes 0.1mL medicament to ulcer surface.Respectively at 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days of administration, respectively with
Machine puts to death 2 SD rats, completely removes ulcer mucous membrane, observes canker sore mucous membrane face, and vernier caliper measurement calculates ulcer area.
Test result:
1) two groups of rat different time canker sore areas compare
After modeling, glycerol control group constantly reduces with experimental group SD rat canker sore area.0 day, 1 day glycerol pair is administered
According to group and experimental group ulcer area no significant difference, experimental group ulcer area is less than control group after administration 2 days, 3 days, and difference has
Statistical significance (P < 0.05), 8 days two groups of ulcer mucous membranes of administration heal.
2) two groups of rat oral cavity mucous membrane tissue pathological observations
Administration 1 day, still visible oedema and surface covers yellow-white pseudomembrane around glycerol control group and experimental group ulcer.Mirror
Lower observation lamina propria has a large amount of inflammatory cell infiltrations, based on neutrophil leucocyte.Administration 3 days, glycerol control group skin surface is still
The covering of visible part pseudomembrane, experimental group pseudomembrane fall off substantially, and visible experimental group blood capillary proliferation is obvious under mirror.Administration 6 days, mirror
Lower observation glycerol control group still has a large amount of inflammatory cell infiltrations, and experimental group epithelial repair is obvious.After administration 8 days, experimental group is burst
Ulcer range is unobvious, basic to heal.Visible two groups of epithelial repairs are basically completed under mirror.
Four, skin anaphylactic test
Cavy 30 are taken, is randomly divided into 3 groups by gender, weight, every group 10, half male and half female is respectively as follows:
1) blank control group (physiological saline for being coated with equivalent)；
2) experimental group (drug that drug embodiment 1,2 or 3 is formulated prevention or treatment mouth disease obtained)；
3) positive drug control group (positive sensitizing drugs 2,4- dinitrofluorobenzene, 1% sensitization concentration and 0.1%
Excite concentration).
Sensitization contact: for 24 hours in guinea pig back two sides before test, cut off or shave the skin in animal trunk back tested material area
Hair, when unhairing, answer extreme care, not damage skin in order to avoid cutaneous permeability.It applies surface product and accounts for about animal body surface area
10%.Using maximum dosage-feeding method, dosage 5g/kg.
Experimental group: the drug for giving the prevention obtained of the formula of embodiment 1,2 or 3 or treatment mouth disease is coated in back part of animal
Left side hair removal section, is then covered with thin film, and non-stimulated immobilization with adhesive tape prevents animal from licking, and is kept for 6 hours.7th day and
Fortnight is in kind respectively repeated 1 times, and is amounted to 3 times.
Blank control group (physiological saline for being coated with equivalent) and positive drug control group (2,4- dinitro of positive sensitizing drugs
Base chlorobenzene, 1% sensitization concentration and 0.1% excitation concentration) method is same as above.
Excitation contact: 14 days after last dose tested material sensitization, test medicine (2g/kg) is applied to depilation on the right side of cavy
Area, positive controls the 2 of concentration 0.1% (, 4- dinitrofluorobenzene) are removed tested material after 6h, are observed at once, then in 24,48,
Cutaneous anaphylaxis situation is observed after 72h again, by 2 scale of table, and evaluates sensitization degree.
Table 2: cutaneous anaphylaxis degree standards of grading
Skin anaphylactic test result: after the tested area's self-excitation administration 6h of positive controls animal skin, by obvious slight red
Spot occurs, no oedema, sensitization rate 100%.Test group of animals self-excitation is administered 6~72h and does not occur erythema and oedema, with blank pair
According to a group indifference.It can be seen that experimental group does not generate sensitivity response.
Table 3: influence of the drug to guinea pig skin allergy
Five, preparation stability is tested
The purpose of stability test is that investigation material medicine or preparation become at any time under the influence of temperature, humidity, light
The rule of change provides scientific basis for the production of drug, packaging, storing, traffic condition, while establishing having for drug by test
The effect phase.Preparation stability, in order to improve the quality of the pharmaceutical preparations, guarantees pharmaceutical effectiveness to being safely and effectively very important for preparation is guaranteed
With safety, it is necessary to pay attention to and study the stability of preparation.
The test of 5.1 influence factors
It (lot number: 160801) is set according to the drug test product that embodiment 1,2 or 3 is formulated obtained prevention or treatment mouth disease
In surface plate, respectively at items such as strong illumination (4500LX ± 500LX), high temperature (60 DEG C) and high humiditys (25 DEG C, RH90% ± 5%)
It is placed 10 days under part, it is separately sampled when the 5th, 10 day, and compared with 0 day with batch sample data, under the above conditions except measurement
Outside related content of material, also need to observe its sample variation, observation index is the Elemental characters such as appearance, the color of drug dressing, examination
It tests and the results are shown in Table 4.
Table 4: influence factor experiment investigation result
The result shows that fourth in the pharmaceutical preparation of prevention or treatment mouth disease obtained should be formulated according to embodiment 1,2 or 3
Fragrant phenol and the stability test of iodoform content be it is metastable, and the Elemental characters such as the adhesion strength of preparation, appearance, color without
Significant change.
5.2 accelerated test
The drug for being formulated prevention or treatment mouth disease obtained according to example 1,2 or 3 is applied, test sample 3 batches, commercially available back
(lot number: 160801,160802,160803), placing 6 months under conditions of 30 DEG C ± 2 DEG C of temperature, relative humidity 65 ± 5%,
1st month during test, 2 months, 3 months, 6 the end of month it is separately sampled primary, and compared with 0 month with batch sample data,
Under above-mentioned condition in addition to measuring related content of material, also need to observe its sample variation, observation index is the appearance of drug dressing, color
The Elemental characters such as pool, test result are shown in Table 5.
Table 5: accelerated test investigates result
The result shows that fourth in the pharmaceutical preparation of prevention or treatment mouth disease obtained should be formulated according to embodiment 1,2 or 3
Fragrant phenol and the stability test of iodoform content be it is metastable, and the Elemental characters such as the adhesion strength of preparation, appearance, color without
Significant change.
5.3 long term test
It will be formulated prevention obtained according to embodiment 1,2 or 3 or treat the drug of mouth disease, test sample 3 batches, commercially available packet
Dress (lot number: 160801,160802,160803), places 24 under conditions of 30 DEG C ± 2 DEG C of temperature, relative humidity 65 ± 5%
Month, sampling in every 3 months is primary, samples respectively at 3,6,9,12,18,24 months, and compared with 0 month with batch sample data, upper
Under the conditions of stating in addition to measuring related content of material, also need to observe its sample variation, observation index is the appearance of drug dressing, color
Equal Elemental characters, test result are shown in Table 6.
Table 6: long term test investigates result
The result shows that being formulated according to embodiment 1,2 or 3 in the drug of prevention or treatment mouth disease obtained, eugenol
It is with the stability test of iodoform content the result is that metastable, and the Elemental characters such as adhesion strength, appearance, color become without obvious
Change.
Influence factor test result shows the medicine that prevention or treatment mouth disease obtained is formulated according to embodiment 1,2 or 3
Object, indices are stable under high temperature, high humidity, illumination condition, therefore embodiment 1,2 or 3 is formulated prevention or treatment obtained
The holding conditions of the drug of mouth disease are drafted as shading, are sealed.
Through accelerated test 6 months, long term test 24 months after simulation listing packaging, every quality investigation refers to three batches of samples
Mark is stable, and will temporarily draft the formula of embodiment 1,2 or 3 validity period obtained prevented or treat mouth disease drug is 24
Month.
Six, cooling effect is studied
Rabbit 36 are taken, is randomly divided into 9 groups, every group 4,3% Nembutal sodium solution 30mg/kg intraperitoneal injection of anesthesia,
Rabbit back hair, area about 8cm × 6cm are removed with operating scissors and vulcanized sodium.After routine disinfection, removing blank group external application tweezers will
Skin lifts, skin holostrome under operating scissors Transverse Shear, forms the Ulcer Models (i.e. model control group) of full thickness dermal.With red
Outside line body temperature measures local temperature, continues 2min, front and back comparison.
After modeling, compared to the blank group, each group rabbit local skin temperature is apparently higher than blank group (P < 0.01), there is system
Meter learns meaning, shows that the Ulcer Models of full thickness dermal can cause local skin temperature significantly raised；Each group skin temperature
Statistical analysis P > 0.05 shows each group defect skin temperature indifference after modeling, is comparable.By embodiment 1,2 or 3
Drug made from the drug and comparative experiments example 1~6 of formula prevention obtained or treatment mouth disease is covered in the surface of a wound and adds again
Thin film, non-stimulated immobilization with adhesive tape, administration time 1h measure local temperature at rabbit defect of skin again after administration.
Table 7: prevention or treatment mouth disease drug to rabbit defect of skin model cooling effect observation (N=4)
Note: comparative experiments example is compared with embodiment 1,2 or 3 after * administration, P < 0.05.
Test result is shown, after medication, compared with model control group, embodiment 1,2 or 3 and comparative experiments example 2,3,4,5,
6 rabbit temperature change is obvious (P < 0.01), statistically significant；Illustrate local anaesthetics and caryophyllus oil, peru balsam, rhizoma cibotii hair
(gelfoam, chitosan) interaction plays good collaboration cooling effect, and temperature at the surface of a wound drops in local anaesthetics therein
It is low, the dysfunctions such as the local red and swollen heat pain of damaged skin are eliminated rapidly.
Seven, anastalsis research
Rabbit 35 are taken, is randomly divided into 7 groups, every group 5, anesthesia is fixed, ear's depilation, disinfection, with scalpel from rabbit ear
The wound of a 1cm long, including ear's aorta are cut at have sharp ears 1/3, record time T1.After 3s, by embodiment 1,2 or
Drug made from the drug and comparative experiments example 1~6 of the prevention obtained of 3 formulas or treatment mouth disease is covered in the surface of a wound and adds again
Thin film, non-stimulated immobilization with adhesive tape are pressed with 50g counterweight, siphon away surrounding oozing of blood.Drug used in each group weighs up gross weight in advance
W1.The surface of a wound is observed whether there is or not blood exudation, blood terminates until 10s not oozing of blood, records time T2.Dressing gross weight after weighing hemostasis
Measure W2.Calculate amount of bleeding W and bleeding stopping period T.
T=T1- T2.W=W1- W2.It the results are shown in Table 8.
Table 8: prevention or treatment mouth disease drug to rabbit ear wound hemostasis effect observation (N=5)
Note: * is compared with embodiment 1,2 or 3, P < 0.05
Test result shows, the amount of bleeding of comparative experiments example 1,2,5,6 and bleeding time obviously higher than embodiment 1,2 or
3, illustrate that caryophyllus oil, peru balsam, rhizoma cibotii hair (gelfoam, chitosan) and local anaesthetics interaction play good collaboration
Haemostatic effect, local anaesthetics therein reduce temperature at disease damage, eliminate the dysfunctions such as the local red and swollen heat pain of mucous membrane rapidly.
Eight, analgesic activity is studied
Female mice is taken to be placed on constant temperature hot plate, temperature is maintained at (55 ± 0.5) DEG C range, licks metapedes with mouse to see
Index is examined, record mouse, up to occurring licking the time of metapedes because of stimulation for the mouse pain incubation period, selects pain from hot plate is placed on
Mouse of the pain incubation period between 10~30s is qualified (to prevent mouse foot from scalding, setting deadline as 60s).Take conjunction
Lattice mouse 70, it is randomly divided into 7 groups, every group 10.Respectively by embodiment 1,2 or 3 after measurement mouse normal pain incubation period
Drug and 1~6 drug of comparative experiments example and clear film are covered in the surface of a wound, then add the non-stimulated immobilization with adhesive tape of thin film,
Administration time 4h measures mice pain incubation period again after administration.It the results are shown in Table 9.
Table 9: prevention or treatment mouth disease drug to the mouse threshold of pain influence (N=10)
Note:#Each group is compared with before administration, P < 0.05；* comparative experiments example is compared with embodiment 1,2 or 3 after being administered, P <
0.05。
Test result is shown, prevents or treat the drug and comparative experiments of mouth disease made from embodiment 1,2 or 3 prescriptions
The drug of example 3,4,5,6, after mouse pain threshold has conspicuousness raising, comparative experiments example 1,2 to be administered compared with before administration after administration
Mouse pain threshold is significantly lower than the drug of embodiment 1,2 or 3, and it is good to illustrate that caryophyllus oil, lidocaine interaction play
Synergic antalgic effect.
Nine, Antibacterial Activity
KB disk diffusion method measures the prevention obtained of embodiment 1,2 or 3 or the vitro Drug for the treatment of mouth disease inhibits thin
The effect of bacterium growth.
The medicine of the drug and comparative experimental example 1~6 of the prevention obtained of the formula of Example 1,2 or 3 or treatment mouth disease
Diameter 6.35mm is added in object, and the drug sensitive test paper of water absorption 20mL makes the scraps of paper and preparation come into full contact with infiltration, spare.
Choose staphylococcus aureus (ATCC25923), Streptococcus mutans (UA159), escherichia coli (ATCC
25922) the pure of 18h~for 24 hours and the oral cavities common pathogen such as porphyromonas gingivalis (ATCC 33277), secondary culture, is selected
Bacterium colony is cultivated, the bacteria suspension of 0.5Mac concentration is prepared into.Corrected bacterium solution is dipped with sterile cotton swab, in inside pipe wall by extra bacterium
Liquid rotation squeeze go after agar surface even spread be inoculated with, 60 degree of each Rotating Plates, finally along plate inner edge smearing 1 week.It applies
The plate of cloth bacterium solution is dried at room temperature for 3min~5min, and the drug containing scraps of paper are close to agar surface with aseptic nipper.Two scraps of paper
The spacing at center should be greater than 24mm, and the edge of the center anomaly plate of the scraps of paper should be greater than 15mm.Plate is inverted in 15min.Paper
It can constantly be spread to scraps of paper peripheral region after moisture dissolution in medicament extraction agar contained in piece, form the concentration successively decreased
Gradient, the growth of bacterium to be checked is suppressed within the scope of Mlc around the scraps of paper, to generate transparent inhibition zone.By what is posted
After plate sets 35 DEG C of incubation 18h, with vernier caliper measurement antibacterial circle diameter.It the results are shown in Table 9.
Table 9: antibacterial circle diameter (mm) measurement result (N=3)
Note: * is compared with embodiment 1,2 or 3, P < 0.05；* is compared with embodiment 1,2 or 3, P < 0.01.
Test result shows that caryophyllus oil, peru balsam, iodoform, calcium hydroxide, rhizoma cibotii hair, gelfoam, chitosan have
Certain fungistatic effect, wherein calcium hydroxide is stronger to gram positive bacteria effect, and peru balsam acts on more gram-negative bacteria
By force, Multiple components interaction expands antimicrobial spectrum, plays synergistic effect.
Ten, clinical test
10.1 case selections
It chooses canker sore patient 176 and is used as research object, wherein male 82, women 94, selection criteria:
1) minor aphtha, diagnostic criteria is referring to Ministry of Public Health's programming textbook " oral mucosal disease "；
2) patient is without severe total illness；
3) canker sore is monthly broken out more than once；
4) patient does not take the drug of any treatment canker sore within January, this morbidity is without any treatment；
5) this morbidity is no more than 3d, the age at 15~55 years old, male or female.It is divided into control group and treatment group, two groups of property
Not, age comparing difference is not statistically significant (P > 0.05).
10.2 medications
Treatment group patient is affixed on ulcer using the drug that embodiment 1,2 or 3 is formulated prevention or treatment mouth disease obtained
Position, postprandial and 0.5h patch is used before sleeping with 3 respectively, 5d is as a treatment course；Control group oral vitamin B:210mg, vitamin C:
200mg (during medication, does not use any other drug therapy) 3 times a day.Two groups the 3rd day and the 5th day after medication
Further consultation is observed curative effect, and is recorded.
10.3 the standard of curative effect evaluation
Healing: pain completely disappears in 5 days；
Effective: 2 degree of pain relief or more, other symptoms do not improve；
Effective: 1 degree and 1 degree of pain relief or more, other symptoms do not improve；
Invalid: substantially without alleviation, other symptoms do not improve pain degree.
10.4 statistical procedures
Using X2It examines, is that difference is statistically significant with P < 0.05.
10.5 results
It see the table below 10, as can be seen from the table, the healing rate and effective percentage for the treatment of group are above control group, P < 0.05.
Table 10: treatment group and control group curative effect compare
Claims (5)
1. the drug of a kind of prevention or treatment mouth disease, which is characterized in that the drug is with gelfoam, rhizoma cibotii hair or chitosan
As carrier, using caryophyllus oil, iodoform, calcium hydroxide, peru balsam as effective component, and suitable local anaesthetics composition is added,
Wherein, the local anaesthetics is lidocaine, totokaine, loxoprofen one of which.
2. the drug of prevention as described in claim 1 or treatment mouth disease, which is characterized in that the drug obtained is by following
Raw material and its dosage composition:
Rhizoma cibotii hair: 8.5 parts, lidocaine: 0.01 part, caryophyllus oil: 4.25 parts, iodoform: 4.25 parts, calcium hydroxide: 2 parts, Peru
Face cream: 80 parts.
3. the drug of prevention as described in claim 1 or treatment mouth disease, which is characterized in that the drug obtained is by following
Raw material and its dosage composition:
Gelfoam: 8.5 parts, totokaine: 0.01 part, caryophyllus oil: 4.25 parts, iodoform: 4.25 parts, calcium hydroxide: 2 parts, Peru
Face cream: 80 parts.
4. the drug of prevention as described in claim 1 or treatment mouth disease, which is characterized in that the drug obtained is by following
Raw material and its dosage composition:
Chitosan: 8.5 parts, loxoprofen: 0.01 part, caryophyllus oil: 4.25 parts, iodoform: 4.25 parts, calcium hydroxide: 2 parts, Peru
Face cream: 80 parts.
5. the drug of prevention or treatment mouth disease as described in one of claim 1 to 5, which is characterized in that the medicine
The dosage form selection toothpaste of object, dripping pill, mouthwass, oral cavity spray liquid, mouth gels, oral cavity ointment, oral cavity are used
One of patch, oral cavity cotton balls, medical grade silicon rubber, oral cavity dressing and chewing gum.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910167575.5A CN109908205A (en) | 2019-03-06 | 2019-03-06 | A kind of drug prevented or treat mouth disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910167575.5A CN109908205A (en) | 2019-03-06 | 2019-03-06 | A kind of drug prevented or treat mouth disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109908205A true CN109908205A (en) | 2019-06-21 |
Family
ID=66963528
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910167575.5A Pending CN109908205A (en) | 2019-03-06 | 2019-03-06 | A kind of drug prevented or treat mouth disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109908205A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110840853A (en) * | 2019-10-26 | 2020-02-28 | 张强 | Chewing or buccal type oropharyngeal local anesthetic for gastroscopy and taking method |
-
2019
- 2019-03-06 CN CN201910167575.5A patent/CN109908205A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110840853A (en) * | 2019-10-26 | 2020-02-28 | 张强 | Chewing or buccal type oropharyngeal local anesthetic for gastroscopy and taking method |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Silva et al. | Natural medicaments in endodontics: a comparative study of the anti-inflammatory action | |
| CN106176690B (en) | Hyaluronic acid oral care film and preparation method and application | |
| TW200911279A (en) | Compositions, uses, and method of making wound care products from naturally occurring food ingredients | |
| AT15430U1 (en) | Dental agent based on hyaluronan and octenidine dihydrochloride | |
| RU2550957C1 (en) | Method of treating chronic generalised periodontitis | |
| Chibinski | The use of silver diamine fluoride in pediatric dentistry | |
| CN109908205A (en) | A kind of drug prevented or treat mouth disease | |
| KR100573206B1 (en) | Use of dichlorobenzyl alcohol for preparing a preparation for topical treatment of inflammation and a preparation containing dichlorobenzyl alcohol | |
| CN106474137B (en) | A kind of film for treating oral ulcer containing chlorophyll and preparation method thereof | |
| RU2482859C1 (en) | Method of treating periodontitis and inflammatory diseases of oral mucosa | |
| RU2293557C2 (en) | Agent for topical using in treatment of skin and mucosa tissue disease | |
| Brooks et al. | Ethnobotanical tattooing of the gingiva: literature review and report of a case | |
| RU2657807C1 (en) | Method for treatment of oral candidiasis in patients with removable prosthetic restorations by solkoseril and chophytol drug products | |
| CN109464501A (en) | A kind of pharmaceutical composition preventing and treating alveolitis | |
| CN113271987A (en) | Hydrogel wound therapy | |
| RU2494753C2 (en) | Methods of treating prosthetic inflammatory diseases of oral mucosa | |
| RU2201194C2 (en) | Medicinal film "piyavit" for treatment of inflammatory diseases of parodontium | |
| RU2784519C1 (en) | Method for accelerating wound healing and formation of the mucous membrane of the prosthetic bed | |
| Payne | Is xylitol an effective treatment for oral candida infections? | |
| CN107213056A (en) | A kind of antibacterial yellowish-white toothpaste of anti-inflammatory | |
| RU2725244C1 (en) | Method of treating periodontitis | |
| RU2519100C1 (en) | Method of treating hypertrophic gingivitis | |
| CN107595819A (en) | A kind of Nano diamond modified liquid adhesive bandage and preparation method thereof | |
| RU2289414C1 (en) | Method for treatment of inflammation parodontium diseases | |
| RU2604128C1 (en) | Preparation for treating periodontitis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190621 |