CN108771677A - It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops and preparation method thereof - Google Patents
It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops and preparation method thereof Download PDFInfo
- Publication number
- CN108771677A CN108771677A CN201810418957.6A CN201810418957A CN108771677A CN 108771677 A CN108771677 A CN 108771677A CN 201810418957 A CN201810418957 A CN 201810418957A CN 108771677 A CN108771677 A CN 108771677A
- Authority
- CN
- China
- Prior art keywords
- nasal drops
- rhinitis
- nasosinusitis
- acute
- allergic rhinitis
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Acute and chronic rhinitis, nasosinusitis, the nasal drops of allergic rhinitis and preparation method are treated the present invention relates to a kind of.Its component includes neomycinsulphate, chlorphenamine maleate, naphcon, auxiliary material and solvent, wherein, in per 1000ml nasal drops containing neomycinsulphate 97.5~5,000,000 units, 0.3~1.0g of chlorphenamine maleate, 0.3~1.0g of naphcon.Nasal drops of the present invention has antibacterial, anti-inflammatory, anti-allergic effects, while symptom of having a stuffy nose caused by energy vasoconstriction improvement rhinitis, non-invasive, and easy to carry, and easy to use, effect rapidly, can shorten the course of disease, and patient uses compliance good, and cure rate is high；To acute and chronic rhinitis, nasosinusitis, allergic rhinitis etc. has good therapeutic effect.The processing technology of preparation method of the present invention is simple and practicable, reproducible, is convenient for industrialized production.
Description
Technical field
The present invention relates to a kind of nose section pharmaceutical preparation more particularly to a kind for the treatment of acute and chronic rhinitis, nasosinusitis, allergia nose
Scorching nasal drops and preparation method thereof.
Background technology
Rhinitis, nasosinusitis are clinical common frdquently encountered disease, can induce a variety of upper respiratory diseases, in recent years, air pollution day
Become serious, harmful substance, anaphylaxis substance through nasal inhalation increase, and keep the incidence of rhinitis, nasosinusitis obviously in rising trend.
Children and adolescents schneiderian membrane barrier develops not perfect, antibacterial ability and immunologic hypofunction, to various pernicious gases and sensitizer
Poor resistance, for the group of people at high risk of the disease.The especially symptoms such as failure of memory caused by chronic nasosinusitis, seriously affect patient
School grade.
Currently, the clinical drug and method that there is no ideal treatment nasosinusitis, rhinitis.The systemic administrations such as oral or injection exist
It absorbs, in distributed process, some drugs are destroyed by stomach and intestine, liver or blood circulation shunts, and really reach nasal cavity, sinus cavities lesion
The effective concentration at position is very low, it is difficult to reach therapeutic effect, and can lure germ drug resistance into and so that lesion is switched to chronic, so curative effect
Difference, cure rate are low；Common local application, symptom of having a stuffy nose caused by only there is vasoconstriction to improve rhinitis such as Naphazoline, pharmacology
It acts on that single, drug effect is undesirable, and toxic side effect is big, and rhinitis medicamentosa can be caused.Laser therapy is generated with laser beam
High temperature burns diseased region, with tissue and the pathogenic bacteria of diminishing inflammation, since laser beam cannot reach sinus cavities, therefore can only be used to nose
Scorching and nasal polyp treatment, it is invalid to nasosinusitis, and laser therapy have it is traumatic, it is cumbersome, it is costly.Therapy is punctured, is used
Puncture needle wears out lateral wall of nasal cavity bone plate and enters sinus cavities, first extracts secretion and fester, then liquid is injected in sinus cavities and is controlled
Treat nasosinusitis, though it is effective in cure because it is with traumatic, patient's more pain and cannot adhere to, therefore curative effect cannot be consolidated.Spray
Agent sprays into liquid in nasal cavity, locally generating antibacterial, antiinflammation, can be used for treating rhinitis, because cannot directly spray liquid
Enter in nasal cavity, it is nearly unavailable to nasosinusitis.
The above drug and method, or really arrival nasal cavity, the active drug concentration of sinus cavities diseased region are too low；Or pharmacology
Act on single, toxic side effect is big；Or drug cannot reach sinus cavities or method there is traumatic patient more pain and cannot be hard
It holds；Or operating method is cumbersome, costly.Thus currently used for clinical treatment nasosinusitis, the drug of rhinitis and method, exists and take effect
Slowly, poor efficacy, long course for the treatment of, cure rate is low, toxic side effect is big, patient spends the defects of more.
Invention content
The purpose of present invention is to overcome drawbacks described above, according to nasosinusitis, the pathogenic factors of rhinitis, pathologic, physiologic and nose
The anatomical features of chamber, sinus cavities, provide it is a kind of treat acute and chronic nasal sinusitis, rhinitis, the compound medicinal formulation of allergic rhinitis and
Preparation method, the compound preparation drug effect mutually cooperate with, and have the function of antibacterial, anti-inflammatory, antiallergy, shrink nasal mucosa vessels,
There is optimum quantum of utilization that is unique, can reach effective therapeutic dose simultaneously, there is synergistic effect after three kinds of active ingredient combinations, it can
The content for reducing drug alone, to increase substantially curative effect, reduce toxic side effect.
The present invention is to solve above-mentioned technical problem by the following technical programs：
It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops, which is characterized in that the nasal drops
At being grouped into：Neomycinsulphate, chlorphenamine maleate, naphcon, auxiliary material and solvent, wherein per 1000ml drops
Containing the unit of neomycinsulphate 97.5~5,000,000 in nose liquid, 0.3~1.0g of chlorphenamine maleate, naphcon 0.3~
1.0g。
Preferably, the auxiliary material includes preservative, and the preservative is ethyl hydroxy benzoate.The auxiliary material includes that nose locally may be used
It is configured to nasal drops with preparation described in the pharmacy of receiving.Preservative is subjected to any type described in pharmacy and is suitable for
The bacteriostatic agent of nasal drops.
Preferably, 0.10~0.40g containing ethyl hydroxy benzoate in every 1000ml nasal drops.
Preferably, the auxiliary material includes osmotic pressure regulator, and the osmotic pressure regulator is sodium chloride, and per 1000ml
Sodium chloride-containing 8.9g in nasal drops.Osmotic pressure regulator is subjected to the infiltration that any type described in pharmacy is suitable for nasal drops
Press conditioning agent.
Preferably, the solvent is ethyl alcohol and purified water.
Preferably, contain 162.5 ten thousand unit of neomycinsulphate, chlorphenamine maleate in every 1000ml nasal drops
0.4g, naphcon 0.4g.
Preferably, the nasal drops includes neomycinsulphate, chlorphenamine maleate, naphcon, oxybenzene
Ethyl ester, sodium chloride, ethyl alcohol and purified water, wherein contain 162.5 ten thousand unit of neomycinsulphate, Malaysia in per 1000ml nasal drops
Sour chlorphenamine 0.4g, naphcon 0.4g, ethyl hydroxy benzoate 0.25g, sodium chloride 8.9g, 2.5mL ethyl alcohol and purified water.
It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops preparation method, step is specifically such as
Under：
The preservative for taking recipe quantity, after adding ethyl alcohol dissolving that 10% ethanol solution is made；The preservative ethyl alcohol of gained is molten
Liquid is added in hot purified water, cooling, sequentially adds chlorphenamine maleate, naphcon, neomycinsulphate, osmotic pressure
Conditioning agent stirs to dissolve, filtering, add purified water to full dose constant volume, stir evenly, packing to get.
Preferably, the preservative is ethyl hydroxy benzoate, and the osmotic pressure regulator is sodium chloride.
A kind of application of the nasal drops in Rhinological disease for treating acute and chronic rhinitis, nasosinusitis, allergic rhinitis.
Compared with prior art, the present invention has the advantages that：
Active ingredient hydrochloric acid naphazoline is alpha-receptor agonist in invention formulation, has the work for shrinking nasal mucosa vessels
With reducing the exudate of blood vessel, it is congested to mitigate schneiderian membrane swelling, is clinically used to treat cold allergic rhinitis, inflammatory nose
Congested, acute and chronic rhinitis；Active constituent chlorphenamine maleate also known as chlorpheniramine are H1 receptor antagonists, are antihistaminic medicines,
With anti-allergic effects, be mainly used for rhinitis, skin and mucosa allergy and alleviate shed tears, sneeze, the cold symptoms such as runny nose；Activity
Ingredient neomycinsulphate is aminoglycoside antibiotics, all effective to Gram-positive and negative bacterium, eye drops is made, to Portugal more
Grape Coccus, corynebacterium have good action, and the present invention can be made also to disappear with antibacterial while treating rhinitis, nasosinusitis
Scorching effect.Invention formulation has antibacterial, anti-inflammatory, antiallergy and vasoconstriction effect, is suitable for acute and chronic nasal sinusitis, allergy
Property rhinitis etc..
1, the present invention is a kind of nasal drop for treating rhinitis, nasosinusitis, allergic rhinitis, directly instills nasal cavity and works.Drop
Nose liquid compensates for the dosage forms such as oral and injection and is absorbing, in distributed process, and some drugs are destroyed by stomach and intestine, liver or blood follows
Ring shunts, the very low disadvantage of the effective concentration to overcome real arrival nasal cavity, sinus cavities diseased region.
2, alpha-receptor agonist naphcon is used in the present invention, antihistaminic medicine chlorphenamine maleate is gone back
Using aminoglycoside antibiotics neomycin, therefore except with nasal obstruction symptom and antiallergy caused by vasoconstriction improvement rhinitis
Effect outside, also have antibacterial and anti-inflammation functions, rhinitis medicamentosa will not be caused.Three's combination can play pharmacology synergistic effect, tool
Have and heightens the effect of a treatment, reduces the effect of toxic side effect being used for a long time.
3, the present invention is a kind of nasal drops, instills nasal cavity and works, non-invasive, and easy to carry, and easy to use, patient makes
It is good with compliance.
4, for the present invention compared with nasal spray on the market, liquid, which can not only reach, can also flow into nasal sinus in nasal cavity, because
This has good therapeutic effect to rhinitis and nasosinusitis.
5, the present invention proves the ratio for using formula as most ratio of greater inequality through experimental study, and the drug after adjusting component proportioning is treated
Effect can be declined.
6, the processing technology of preparation method of the present invention is simple and practicable, reproducible, is convenient for industrialized production.
Below just in conjunction with the embodiments, the embodiment of the present invention is described in further detail, so that the technology of the present invention
Scheme is more readily understood, grasps.
Specific implementation mode
Embodiment 1
Contain ethyl hydroxy benzoate 0.25g, 162.5 ten thousand unit of neomycinsulphate, chlorphenamine maleate in per 1000ml preparations
0.4g, naphcon 0.4g, sodium chloride 8.9g, 2.5mL ethyl alcohol and purified water.
Embodiment 2-6, comparative example 1-4 such as following tables are set
It is a kind of treat acute and chronic nasal sinusitis, rhinitis nasal drops preparation method, step is specific as follows：
The preservative for taking recipe quantity, after adding ethyl alcohol dissolving that 10% ethanol solution is made；The preservative ethyl alcohol of gained is molten
Liquid is added to 250mL, cooling in 100 DEG C of hot purified water, sequentially adds chlorphenamine maleate, naphcon, sulfuric acid
Neomycin and osmotic pressure regulator etc., stir to dissolve, and filtering adds purified water to full dose constant volume, stirs evenly, and dispenses,
To obtain the final product.
In above method, each component prepares raw material according to proportioning in embodiment and prepares.
Increase simultaneously and has listed nasal spray as a comparison case, comparative example 5 (naphcon nasal drops, 1000ml liquids
Naphazoline containing 1g, what Ji metric system pharmaceutical factory of Guangzhou Baiyunshan Pharmaceutical Group Co., Ltd. White Cloud Mountain) and 6 (compound of comparative example
Naphazoline spray, 1000ml liquids naphazoline containing 0.5g, 1g chlorphenamine maleates, the limited public affairs of Nanjing Xing Yin medicine companies group
Department).
1 nasal drops of experimental example causes histamine the inhibiting effect that Rat Nasal Mucosa capillary permeability increases
1. experiment purpose
It causes Rat Nasal Mucosa capillary permeability to increase by histamine and establishes animal model, investigate and compare each prescription to group
The inhibiting rate of amine effect treats rhinitis for it, nasosinusitis curative effect of medication provides theoretical foundation.
2. experimental principle
Histamine is a kind of inflammatory mediator, its release can cause local capillary permeability to increase and inflammatory cell leaching
Profit makes pigment penetrate blood vessel, OD values can be measured by ultraviolet spectrophotometry.
3. material and reagent
3.1 experimental animal
SPF grades of SD male rats, 150~200g, Zhongshan University's Experimental Animal Center, experimental animal production licence number
For：SCXK (Guangdong) 2011-0029；Quality of Experimental Animals quality certification number：44008500012088.Animal is disposed in experimentation
Meet animal ethics standard.
3.1.1 rearing conditions
Temperature：20~25 degrees Celsius；Humidity 40%~70%
Rate of ventilation：More than 10 times/disappearance
Stocking density：6/cage
Lighting hours：12 hours (mornings 7：00 turns on light~afternoon 7：00 turns off the light)
3.1.2 feed and drinking-water
SPF grades of size mouse feeds, freely absorb, are stored between special feed, keep ventilation, cleaning and drying.Feed is normal
Nutritional ingredient index is advised through Guangdong Province experimental animal detection institute (with reference to National Standard of the People's Republic of China GB14924.3-
2010) it detects, annual detection is twice.
Drinking water is freely absorbed through drinking water for animals bottle.Drinking water is through 121 DEG C of (1.0kg/cm2), 30min aqua sterilisas, meet
《Direct drinking water water standard》(CJ94-2005).
3.2 instrument
104 electronic balances of TLE, Mettler-Toledo Instrument (Shanghai) Co., Ltd.；CO2Insulating box, PYX-DHS,
Forma Scientific；TU-1800 ultraviolet-uisible spectrophotometers, Beijing Puxi General Instrument Co., Ltd；Operation
It cuts, ophthalmic tweezers etc..
3.3 reagent
Each embodiment and comparative example (Sun Yat-sen Memorial Hospital)；Yellow Jackets, histamine, Evans blue (by
Pharmaceutical college of Zhongshan University provides).
4. experimental method
4.1 grouping
Examples 1 to 6 group, 1~6 group of comparative example, physiological saline group and diphenhydramine group, Gong Shisige groups, every group 10
SD rats.
4.2 administration
Six groups of embodiments and six groups of comparative examples are administered by the nasal drops of corresponding prescription respectively, physiological saline group and benzene sea
Lamine (a concentration of 12.5mg/mL) is organized and uses physiological saline and Compound Diphenhydramine Hydrochloride nasal drops collunarium respectively, successive administration 7d, daily
Three times, it is dripped every time per side nostril two.
The measurement of 4.3 inhibiting rates
With 3% yellow Jackets 0.1mL100g after last dose 45min-1Anesthesia, 1.5% Evans blue root of Chinese trichosanthes are molten
Liquid 1mL100g-1, every group with 10 newly prepared-3mol.L-1Histamine solution collunarium, per 50 μ L of side.Each group animal is after collunarium
5min opens chest, cuts off atrium dextrum, and aorta, saline infusions, until atrium dextrum efflux turns clear are punctured through left ventricle.
Nasal cavity is splitted through median sagittal plane, removes respiratory region whole schneiderian membrane, 2mm × 2mm fritters is cut into, is put into after scales/electronic balance weighing
In tool plug test tube added with 5mL formamides, be placed in 37 DEG C of insulating boxs, filtered after 48h, with ultraviolet-uisible spectrophotometer in
620nm wavelength colorimetrics calculate the inhibiting rate [inhibiting rate (%)=(physiological saline group OD values-medication group OD to antihistamine effect
Value)/physiological saline group OD value × 100%].
5. statistical method
All measurement datas useIt indicates, the conspicuousness of mean difference carries out variance with 10.0 statistical softwares of spss
Analytical control.
6. experimental result
1 rhinitis of table leads to the inhibiting rate (n=10) of each example antihistamine of nasal drops
Note：Compared with physiological saline group, * p < 0.05, * * p < 0.01
By the comparison of embodiment, with the increase of dosage in the presence of being as a result shown in three kinds of active constituents all,
The inhibiting rate that prescription increases capillary permeability caused by histamine is higher and higher, and different auxiliary material is to capillary permeability
Change does not have a significant impact；And by the comparison of comparative example 1-4, no matter display lacks which kind of active constituent can all make inhibiting rate
It decreases, especially chlorphenamine maleate；Comparative example 5 and comparative example 6 can reach certain inhibiting rate, but less than implementation
Example.It can be seen that embodiment 1 is more more obvious than the antihistamine effect of positive control diphenhydramine nasal drops group simultaneously.
Influence (allergic rhinitis model) of 2 nasal drops of experimental example to ovalbumin sensitization
1. experiment purpose
The effect for comparing each embodiment and comparative example resisting allergic rhinitis, for its treat allergic rhinitis provide it is theoretical according to
According to.
2. experimental principle
Ovalbumin can induce rat generation and scratch the allergic symptoms such as nose, runny nose, sneeze, and mucous membrane eosinophils (EOS) increase
More, IgE contents increase, and ovalbumin rat is the common model of allergic rhinitis.
3. material and reagent
3.1 experimental animal
SPF grades of SD rats, male and female dual-purpose, 150~200g, Zhongshan University's Experimental Animal Center, experimental animal production permit
Card number is：SCXK (Guangdong) 2011-0029；Quality of Experimental Animals quality certification number：44008500012088.To animal in experimentation
Disposition meets animal ethics standard.
3.1.1 rearing conditions
Temperature：20 DEG C~25 degrees Celsius；Humidity 40%~70%
Rate of ventilation：More than 10 times/disappearance
Stocking density：6/cage
Lighting hours：12 hours (mornings 7：00 turns on light~afternoon 7：00 turns off the light)
3.1.2 feed and drinking-water
SPF grades of size mouse feeds, freely absorb, are stored between special feed, keep ventilation, cleaning and drying.Feed is normal
Nutritional ingredient index is advised through Guangdong Province experimental animal detection institute (with reference to National Standard of the People's Republic of China GB14924.3-
2010) it detects, annual detection is twice.
Drinking water is freely absorbed through drinking water for animals bottle.Drinking water is through 121 DEG C of (1.0kg/cm2), 30min aqua sterilisas, meet
《Direct drinking water water standard》(CJ94-2005).
3.2 instrument
104 electronic balances of TLE, Mettler-Toledo Instrument (Shanghai) Co., Ltd.；CO2Insulating box, PYX-DHS,
Forma Scientific；Inverted light microscope, IX51-32PH, Olympus；TDZ4-WS centrifuges, the centrifugation of Changsha Hunan instrument
Machine Instrument Ltd.；Operating scissors, ophthalmic tweezers etc..
3.3 reagent
Each embodiment and comparative example (Sun Yat-sen Memorial Hospital)；Yellow Jackets, ovalbumin sensitization liquid (by
Pharmaceutical college of Zhongshan University provides)；Loratadine (Xian-Janssen Pharmaceutical Ltd.).
4. experimental method
4.1 modeling
Take rat, be injected intraperitoneally ovalbumin sensitization liquid 1mL, the next day it is primary, totally 7 times, this is basic sensitization, basic sensitization
After the next day with 5% ovalbumin exciting liquid collunarium, per 10 μ L of side, rat behavior changes and (scratches in 30min after observation excitation
Nose, runny nose, sneeze etc.), experimental rat behaviouristics score is recorded, remembers total score by the standard addition method, is greater than or equal to 5 per mouse total score
It is divided into modeling success, it is that modeling fails (standards of grading are shown in Table 2) to be less than 5 points of persons.
2 allergic rhinitis rat Syndrome Scale standard of table
4.2 groupings and administration
Choose the successful rat of modeling, be randomly divided into 14 groups, Examples 1 to 6 group, 1~6 group of comparative example, blank group and
Loratadine (1mg/kg) group, every group of 10 SD rats.Intranasal administration after excitation, daily excitation is primary, continuous 14 days, until real
End is tested, physiological saline group experimental rat gives physiological saline collunarium.
4.3 take sample and detection
After experiment, by rat with 3% yellow Jackets 0.1mL100g-1Anesthesia, dorsal position are fixed on animal surgery
On platform, stomach wall is cut off, exposure abdominal aorta is taken a blood sample by abdominal aorta, is positioned in sample collection tube, after being stored at room temperature 2h,
2000rpm/min centrifuges 10min, takes supernatant, is respectively charged into the EP pipes of 1.5mL, is put into -80 DEG C of refrigerators and freezes standby survey.Greatly
Y interferon (INF- γ), interleukin 4 (IL-4) and immunoglobulin E (IgE) content are examined with ELISA method in mouse serum
It surveys.
5. statistical method
All measurement datas useIt indicates, the conspicuousness of mean difference carries out variance with 10.0 statistical softwares of spss
Analytical control.
6. experimental result
6.1 animal behavioral study
After model excitation, animal occurs obviously scratching the symptoms such as nose, runny nose, sneeze, and medication group symptom is substantially reduced.Utilize table
After 2 are scored, there were significant differences compared with physiological saline group for medication group.Each group scoring is shown in Table 3.
3 rhinitis of table leads to each example of nasal drops to allergic rhinitis model treatment grade form (n=10)
Note：Compared with physiological saline group, * p < 0.05, * * p < 0.01
The results show that each embodiment can rat allergic rhinitis caused by substantially reduced ovalbumin scratch nose, runny nose and spray
Symptom is sneezed, and is increased with activity component concentration, the effect of resisting allergic rhinitis is more notable.And comparative example 1-4 each groups are to above
Remission is less apparent, and comparative example 5 and comparative example 6 also have symptom notable alleviation.The effect of 1 resisting allergic rhinitis of embodiment
It is more stronger than Loratadine positive group.
6.2 cell factors change
4 rhinitis of table leads to cell factor variation table (n=10) after each example administration of nasal drops
Note：Compared with physiological saline group, * p < 0.05, * * p < 0.01
As a result it shows that each administration group can increase INF- γ concentration in serum, the concentration of IL-4 and IgE in serum is reduced, to subtract
Subinflammation is reacted.The influence of 1-4 pairs of three kinds of factors of comparative example is not notable, and comparative example 5 and comparative example 6 can subtract to a certain extent
Subinflammation is reacted, and embodiment has a significant impact to each factor and has concentration dependence.
3 bullfrog maxilla ciliary toxicity of experimental example is studied
1. experiment purpose
Compare ciliary toxicity of each embodiment and comparative example to bullfrog, be nasal drops irritation on mucous membrane for theoretical foundation.
2. experimental principle
Bullfrog oral cavity mucous membrane is more sensitive, and being easy to generate in the larger drug of contact stimulus to damage keeps maxilla fine
Hair stop motion.Therefore after different pharmaceutical administration, using the time indirect reflection of in vitro rear bullfrog maxilla fibre swing and its
Contact the irritation on mucous membrane of drug.
3. material and reagent
3.1 experimental animal
Bullfrog, 500g ± 50g.
3.2 instrument
104 electronic balances of TLE, Mettler-Toledo Instrument (Shanghai) Co., Ltd.；Leica light microscopes；Operation
It cuts, ophthalmic tweezers etc..
3.3 reagent
Each embodiment and comparative example (Sun Yat-sen Memorial Hospital)；1% deoxysodium cholate is (by Zhongshan University's pharmacy
Institute provides).
4. experimental method
4.1 grouping
42 bullfrogs are randomly divided into 14 groups, physiological saline group is blank control group, and 1% deoxysodium cholate group is the positive
Control group, remaining is six embodiments and six comparative example groups.
4.2 method
Bullfrog is lain on the back with rope and is fixed on hardboard, 0.5mL liquids (about 10 drop) are added dropwise at maxilla mucous membrane, make medicine
Liquid is totally submerged maxilla, after keeping state 30min, sundries at bullfrog oral cavity and mucous membrane is gently rinsed with physiological saline, carefully
The mucous membrane between two is cut, size is 2mm × 2mm, and every bullfrog is separable to obtain 3 parts of mucous membranes, is gently rushed with physiological saline
Wash clean, mucous membrane is face-up, is laid on glass slide, physiological saline 0.2mL is added dropwise in mucous membrane surface, covered passes through
The swing situation of cilium on 10 × 40 times of optical microphotograph sem observation mucous membranes is subsequently placed at ready in advance added with a small amount of pure water
In the closed environment of chromatography cylinder, vapor is in nearly saturation state.Sample view is taken out every half an hour, if cilium sustained oscillation
It still puts back in chromatography cylinder, until fibre swing stops, to the time of cilium stop motion since administration, when being fibre swing
Between.
The ratio of the cilium persistent movement time of administration group bullfrog and the cilium persistent movement time of physiological saline group bullfrog,
For cilium persistent movement time relative percentage.Drug is to ciliary toxicity reversible action sex determination method：Observe that cilium is put
Dynamic stopping infiltrates mucous membrane with normal saline flushing immediately, observes whether mucociliary swing restores again；If can restore, sentence
Determine drug to be reversible ciliary toxicity effect.
5. statistical method
All measurement datas useIt indicates, the conspicuousness of mean difference carries out variance point with 10.0 statistical softwares of spss
Analysis is examined.
6. experimental result
It is observed under the microscope immediately after removing mucous membrane, as a result shows that the mucous membrane surface of physiological saline group and cilium are clearly complete
Whole, cilia activity is active, rhythmically swings；The visible tissue significantly inactivated of 1% deoxysodium cholate group naked eyes, Jing Xiaguan
It examines cilium to stop swinging quickly, mucous membrane is impaired serious, and cilium falls off substantially, and surface is mixed and disorderly, the visible cell much to fall off of surrounding；
Embodiment 3 and 4 visible part mucous membrane of embodiment are impaired, remaining embodiment and comparative example cilium is substantially without falling off.Each group is specifically fine
The hair persistent movement time is shown in Table 5.
5 rhinitis of table leads to each example of nasal drops to bullfrog maxilla ciliary toxicity result table (n=9)
Note：Compared with physiological saline group, * p < 0.05, * * p < 0.01
The results show that embodiment 3 and 4 cilium persistent movement time of embodiment, there were significant differences with physiological saline group, remaining
Administration group and physiological saline group are more without significant difference, i.e., without apparent irritation on mucous membrane.
4 clinical research of experimental example
It is preparation in institute of the court that the rhinitis produced by embodiment 1, which leads to nasal drops, is applied for many years in our hospital, curative effect and peace
Full property is obtained for the confirmation of clinical expert.
Nasal drops made from embodiment 1-6 and comparative example 1-6 is carried out clinical test by this research.
1. research object
1.1 case selection
It is all enter a group research patient received both from Sun Yat-sen Memorial Hospital's ear-nose-throat department outpatient service and inpatient department
It controls.
1.2 diagnostic criteria
With reference to《The principle of diagnosis and treatment and suggested design of allergic rhinitis》(Chinese Journal of Otorhinolaryngology Head And Neck Surgery editor committee member
Meeting, hals,Nasen und Ohrenheilkunde branch of Chinese Medical Association, 2004, Lanzhou), the diagnosis mark of the allergic rhinitis (allergic rhinitis) of formulation
Standard, such as table 6.
6 diagnostic criteria of table
Note：Mainly diagnosed according to first two.
1.3 symptoms, sign scalar quantization standard
7 primary symptom scalar quantization standard of table
*Indicate the quantity of one-time continuous；#Indicate one day number for blowing nose.
8 sign scalar quantization standard of table
1.4 severity extent grade scales
With reference to WHO ARIA2001 work group according to the course of disease, incidence and this disease to the shadow of life in patients
Ring slight, moderate, the severe being divided into the influence of quality of life according to symptom in rank indexing and Tianjin guide in 2015.
It is shown in Table 9.
9 severity extent grade scale of table
2. case is included in and exclusion criteria
2.1 case inclusion criterias
(1) meet the doctor trained in Western medicine diagnosis of allergic rhinitis；
(2) course of disease >=year；
(3) age is in 8~60 one full year of life, male or female；
(4) before enrollment any treatment is not used in one week in all research objects；
(5) informed consent person.
2.2 case exclusion criterias
(1) patient of Aspirin or glucocorticoid or long-acting corticosteroid in long-term or 3 months nearly is needed；
(2) gestation, gestation or nursing period patient are had intention；
(3) merge the serious organic diseases such as the heart, brain, kidney, liver；
(4) patient for bronchial asthma, the atopic dermatitis of occurring together；
(5) the noses patient such as obviously partially bent, nasal polyp or chronic nasosinusitis with nasal septum；
(6) the serious diseases person such as nauseous tumour；
(7) hysteria or mental patient；
(8) receiving to use antihistamine person in specific active immunotherapy or 3d；
(9) other drugs clinical test person is being participated in.
2.3 cases are rejected and the standard that falls off
(1) subject during observation cannot punctual medication, or fail further consultation follow-up on time, can not judge its curative effect person；
(2) judge this curative effect and tolerance using other influences；
(3) for the course for the treatment of not to 1/2, continual cure of being unwilling voluntarily stops curer；
(4) there is serious adverse reaction and interrupt curer.
The processing of 2.4 depigmentation cases
(1) after subject's depigmentation, the modes such as Electricity Federation and subject is taken to get in touch, inquires reason and inquiry record
Last time drips the medicine time, completes the acquisition of related data as far as possible；
(2) for the bad depigmentation patient for the treatment of curative effect, it should which the state of an illness based on the patient makees corresponding treatment；
(3) researcher detailed in case report need to fill in case reasons for dropout and classify.It counts the course for the treatment of and is more than 1/2
The effect of；
(4) correlation circumstance of all observation cases is answered exquisite detail and is retained.
2.5 terminate to test ahead of time
(1) there is sense of discomfort during the experiment in patient, and is possible to influence life security, should stop immediately；For treating
Journey has been more than 1/2, should be included within curative effect statistics；
(2) the medicine less effective that research uses does not have research observation meaning；
(3) there is great bias in research on conceptual design or in implementation process, and drug effect evaluation is queried.
3. research method
3.1 grouping
The Allergic Rhinitis for being included in experiment is divided into embodiment 1-6 and comparative example 1-6, totally 12 groups, every group of 50 people, altogether
600 people, are statistically analyzed, and each group case, without significant difference, is comparable in gender, the course of disease, age, the state of an illness.
3.2 research approach
Every group is that Sun Yat-sen Memorial Hospital Drug Manufacturing Room provide using preparation, and specification is every bottle of 10mL.Each group
The nasal drops of prescription is corresponded to using it, each drop is primary in the morning, afternoon and evening daily, is dripped every time per side nostril 2.Continuous treatment 21 days.Make every time
Before drug, each side nasal cavity clear nasal discharge is first gently blown out, guarantee, which is often dripped, instills nasal cavity.
Every patient is required to deactivate other nasal drops during this period.
3.3 observation item
3.3.1 general data
Name, gender, age, the course of disease, date, occupation, phone, address, general disease history, medical history etc. all should be detailed
Record.
3.3.2 index
The record of primary symptom, the observation situation of nose sign.Respectively patient's body was observed and recorded with the 7th, 14,21 day before the treatment
Situations such as sign and primary symptom, record patient diet, sleep, administration time；Before treatment and treatment detects in peripheral blood on the 21st day respectively
Eosinophile cationic protein's content.
3.3.3 score
Treat preceding and the 7th, 14,21 day inspection record：Concha nasalis inferior and nasal cavity bottom, the relationship of nasal septum；Whether there is or not swollen for concha nasalis inferior
It is swollen, the change of swelling degree and its mucous membrane color and luster；Whether concha nasalis media is visible and whether nasal septum is partially bent, whether has nasal polyp shape
At etc..According to state of an illness difference, it is recorded as 0 point, 1 point, 2 points, 3 points respectively.
Treatment before and observe and record patient's primary symptom within the 7th, 14,21 day, according to the state of an illness difference, be recorded as respectively 0 point, 1 point, 2
Divide, 3 points.
4. result of study
Before 8 groups of treatments and treatment 7 days, treatment 14 days, treatment 21 days total score comparing results be shown in Table 10.
10 8 groups of therapeutic process total score comparisons (n=50) of table
Thus corresponding curative effect can be mapped to table 11.
11 8 groups of therapeutic process Comparison of therapeutic (n=50) of table
It can be seen that by treatment, six prescriptions and comparative example 5 and comparative example 6 of embodiment, treatment 21 days after from
Severe rhinitis has reached slightly, wherein embodiment 1 and embodiment 3~6 treatment 14 days after reach slight, and in comparative example before
After five prescribed treatments, though the state of an illness take a favorable turn, moderate is remained in.
5. adverse reaction
Apparent adverse reaction and toxic side effect do not occur in the treatment for each group patient.
Experiment conclusion
By the above animal and clinical test, comparison finds that each embodiment nasal drops shows preferable antianaphylaxis nose
Scorching curative effect, while capillary vessel of nasal mucosa permeability is increased have good inhibiting effect, still, tests and demonstrate,prove through ciliary toxicity
The higher embodiment 3 of bright dosage and embodiment 4 have certain irritation to schneiderian membrane.And comparative example 1-4 groups are due to lacking portion
Divide active constituent, therefore the equal unobvious of each experimental effect.Comparative example 5 and comparative example 6 have gone out one as the formulations display listed
The effect of fixed alleviation symptom, but its effect is not so good as embodiment 1 significantly.Although it can be seen that single component dose drop after the combination of three medicines
It is low, but because there is synergistic effect between ingredient, still play preferable curative effect.Simultaneously through embodiment 5 and embodiment 6 and in fact
Apply the comparison of example 1, it was demonstrated that auxiliary material used has no significant effect drug effect.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from the spirit and principles of the present invention made by changes, modifications, substitutions, combinations, simplifications,
Equivalent substitute mode is should be, is included within the scope of the present invention.
Claims (10)
1. it is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops, which is characterized in that the nasal drops at
It is grouped into：Neomycinsulphate, chlorphenamine maleate, naphcon, auxiliary material and solvent, wherein per 1000ml collunariums
Containing the unit of neomycinsulphate 97.5~5,000,000 in liquid, 0.3~1.0g of chlorphenamine maleate, naphcon 0.3~
1.0g。
2. the nasal drops for the treatment of acute and chronic rhinitis as described in claim 1, nasosinusitis, allergic rhinitis, which is characterized in that institute
It includes preservative to state auxiliary material, and the preservative is ethyl hydroxy benzoate.
3. the nasal drops for the treatment of acute and chronic rhinitis as claimed in claim 2, nasosinusitis, allergic rhinitis, which is characterized in that every
0.10~0.40g containing ethyl hydroxy benzoate in 1000ml nasal drops.
4. the nasal drops for the treatment of acute and chronic rhinitis as described in claim 1, nasosinusitis, allergic rhinitis, which is characterized in that institute
It includes osmotic pressure regulator to state auxiliary material, and the osmotic pressure regulator is sodium chloride, and often sodium chloride-containing in 1000ml nasal drops
8.9g。
5. the nasal drops for the treatment of acute and chronic rhinitis as described in claim 1, nasosinusitis, allergic rhinitis, which is characterized in that institute
It is ethyl alcohol and purified water to state solvent.
6. the nasal drops for the treatment of acute and chronic rhinitis as described in claim 1, nasosinusitis, allergic rhinitis, which is characterized in that every
Contain 162.5 ten thousand unit of neomycinsulphate, chlorphenamine maleate 0.4g, naphcon 0.4g in 1000ml nasal drops.
7. the nasal drops for the treatment of acute and chronic rhinitis as described in claim 1, nasosinusitis, allergic rhinitis, which is characterized in that institute
The nasal drops stated includes neomycinsulphate, chlorphenamine maleate, naphcon, ethyl hydroxy benzoate, sodium chloride, ethyl alcohol and pure
Change water, wherein contain 162.5 ten thousand unit of neomycinsulphate, chlorphenamine maleate 0.4g, hydrochloric acid naphthalene in per 1000ml nasal drops
First oxazoline 0.4g, ethyl hydroxy benzoate 0.25g, sodium chloride 8.9g, 2.5mL ethyl alcohol and purified water.
8. the nasal drops of a kind for the treatment of acute and chronic rhinitis as described in claim 1, nasosinusitis, allergic rhinitis, step tool
Body is as follows：
The preservative for taking recipe quantity, after adding ethyl alcohol dissolving that 10% ethanol solution is made；The preservative ethanol solution of gained is added
Enter into hot purified water, it is cooling, it sequentially adds chlorphenamine maleate, naphcon, neomycinsulphate, osmotic pressure and adjusts
Agent stirs to dissolve, filtering, add purified water to full dose constant volume, stir evenly, packing to get.
9. as claimed in claim 8 treatment acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops preparation method,
It is characterized in that, the preservative is ethyl hydroxy benzoate, and the osmotic pressure regulator is sodium chloride.
10. a kind of application of the nasal drops in Rhinological disease for treating acute and chronic rhinitis, nasosinusitis, allergic rhinitis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810418957.6A CN108771677A (en) | 2018-05-03 | 2018-05-03 | It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810418957.6A CN108771677A (en) | 2018-05-03 | 2018-05-03 | It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108771677A true CN108771677A (en) | 2018-11-09 |
Family
ID=64027026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810418957.6A Pending CN108771677A (en) | 2018-05-03 | 2018-05-03 | It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108771677A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109568333A (en) * | 2018-12-26 | 2019-04-05 | 江西润泽药业有限公司 | A kind of nasal drops and preparation method thereof for treating rhinitis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103751188A (en) * | 2013-12-31 | 2014-04-30 | 山东天顺药业股份有限公司 | Sodium cromoglycate, naphazoline hydrochloride and chlorpheniramine maleate nasal spray |
-
2018
- 2018-05-03 CN CN201810418957.6A patent/CN108771677A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103751188A (en) * | 2013-12-31 | 2014-04-30 | 山东天顺药业股份有限公司 | Sodium cromoglycate, naphazoline hydrochloride and chlorpheniramine maleate nasal spray |
Non-Patent Citations (1)
| Title |
|---|
| 江霞等: "复方新扑啉滴鼻液质量标准研究", 《今日药学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109568333A (en) * | 2018-12-26 | 2019-04-05 | 江西润泽药业有限公司 | A kind of nasal drops and preparation method thereof for treating rhinitis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Horak et al. | Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy | |
| CN107427502A (en) | Use the smooth treatment method of valley | |
| CN108771677A (en) | It is a kind of treat acute and chronic rhinitis, nasosinusitis, allergic rhinitis nasal drops and preparation method thereof | |
| CN105012487B (en) | Children's nose, which relaxes, leads to nasal drops | |
| CN101332302A (en) | Formula for preparing anti-eczema and cutitis products and preparation method thereof | |
| CN114028384B (en) | Application of liquorice isoflavan derivative in preparation of drug for preventing, relieving or/and treating pruritus | |
| CN101049345A (en) | A preparation for treating disease of oral cavity and gorge, and preparation method | |
| CN109414507A (en) | For preventing and treating the high selectivity adenosine A 3 receptor subtype agonist of neurodegenerative disease | |
| CN102793870A (en) | Chinese herbal medicine for treating renal calculi | |
| US9415064B2 (en) | Prevention or treatment of painful polyneuropathies by administration of an aluminosilicate | |
| CN104784627A (en) | Traditional Chinese medicine externally used film agent used for treatment surgical open or closed injury and preparation method thereof | |
| KS et al. | Different Types of Nasya Karma in Current Practice–A Review | |
| TW581675B (en) | A pharmaceutical composition for use in preventing the onset of asthma in a patient | |
| CN1733147A (en) | Traditional Chinese medicine preparation for treating soft tissue pain and preparation method | |
| WO2019096144A1 (en) | Use of pientzhuang and preparation thereof in treatment of cerebral stroke sequelae | |
| CN101125199B (en) | Application of interleukin 2 in preparing medicine for treating rhinitis | |
| CN109646438A (en) | The application of demethyl coclaurine or its hydrochloride in preparation treatment rhinitis drug | |
| Narine et al. | Conceptual Study of Nasya Karma And Its Various Applications | |
| CN102973571A (en) | New application of fasudil | |
| CN109394776B (en) | Traditional Chinese medicine component formula for treating diffuse interstitial pulmonary fibrosis and application thereof | |
| CN107375422A (en) | Treatment part catarrh symptom liniment and preparation method thereof | |
| CN106038594A (en) | Application of arsenic trioxide in preparation of psoriasis therapeutics | |
| CN105030920A (en) | Traditional Chinese medicinal composition for treating oral ulcer and laryngopathy | |
| Roller et al. | Rosacea. | |
| Amoushahi et al. | Inhalational Ethanol Therapy in COVID-19 Treatment and Prevention |
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 |