CN106727277A - A kind of mentholated nasal cavity in-situ gel spray and preparation method thereof - Google Patents
A kind of mentholated nasal cavity in-situ gel spray and preparation method thereof Download PDFInfo
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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Abstract
The invention discloses a kind of mentholated nasal in situ gel preparation and preparation method thereof.Described nasal in situ gel preparation include menthol, environment-responsive hydrophilic gel matrix, water and acceptable pharmaceutic adjuvant in other pharmacies, acceptable pharmaceutic adjuvant includes but is not limited to solubilizer, preservative, NMF in described pharmacy.Described mentholated nasal in situ gel formulation preparation method is by after appropriate menthol and solubilizer ground and mixed, it is dispersed in environmental sensitivity hydrophilic gel matrix solution, acceptable pharmaceutic adjuvant in other pharmacies is added uniformly to mix, when using with smear, spray or collunarium in the form of nasal-cavity administration, response environment in nasal cavity formed hydrophilic gel.
Description
Technical field
The present invention relates to a kind of nasal cavity in-situ gel preparation with menthol as main ingredient and preparation method thereof.
Background technology
Menthol is by extracting a kind of colourless needles or prism-shaped crystallization or white crystalline that obtain in dried peppermint leaf and stem
Powder, is the main component in peppermint and Peppermint essential oil, there is anti-inflammatory, antipruritic, analgesic, anti-corrosion, stimulation, anesthesia and refrigerant effect.
Menthol external application acts on skin or mucous membrane, can optionally stimulate the frigidoreceptor of human body skin or mucous membrane, produces the sense of cold
Reflection and creeping chill, cause skin and mucosa vessel retraction, play anti-inflammatory, analgesic, it is antipruritic, refrigerant, stimulate circulation, mitigate edema
Deng effect.Under the environment on plateau, arid or cold, due to being air-dried, cold, moisture evaporation is too fast, is easily caused people's nose and glues
Film capillary rupture bleeding, produces nosebleed and rhinitis sicca.The menthol of nasal-cavity administration is slowly penetrated in mucous membrane except tool
Have and moisten and protection nasal membrane effect is outer, effect also with the cytothesis for stimulating schneiderian membrane and prevent nosebleed,
The blood vessel of collapsible deep tissue, while promoting secretion, dilutes sticky mucus, and produces obvious to rhinitis, laryngitis performance
Alleviation and therapeutic action, therefore be usually used in the treatment of rhinitis and nosebleed, but because menthol is atomic molten in water, therefore mesh
Preceding conventional formulation is the menthol nasal drops of the oil-based solvents such as paraffin oil.
Because schneiderian membrane is more sensitive to external irritant, the cilium on surface drives juice to pharynx with the speed of 5-6mm/min
Portion moves, and the medicament of general liquid-type is easily eliminated, so as to greatly shorten medicine in the holdup time only 10-20min of nasal cavity
With the time of contact of na-sal cavity surfaces, directly affect absorption and the curative effect of medicine.The conventional dosage forms of nasal-cavity administration are liquid forms, such as
Nasal drops etc., is vulnerable to the removing of mucociliary, the absorption existing defects of the medicine to that need to have an effect on the whole body, and generally requires frequently
Administration.Using modern medicines preparation technique, extend medicine in the schneiderian membrane residence time and increase medicine by designing novel dosage forms
Thing absorbs, and reduces times for spraying and drug dose, is the effective approach for improving medicine Nasal mucosa absorption and therapeutic effect, wherein
Situ-gel can overcome the shortcomings of nasal drops formulation due to it, it has also become the study hotspot of research of new dosage forms for nasal administration.
Situ-gel (in situ gel), also known as instant-type gel, is a kind of novel medicine feeding carrier sensitive to environmental factor,
The advantage of solution and gel is had concurrently.In-situ gel preparation is at normal temperatures the liquid condition of good fluidity, with solution shape
Formula is administered, agents area because local temperature, the change of ionic strength or pH and there is phase in version in moment, formed it is semi-solid or
Solid pharmaceutical preparation, viscosity is greatly increased, and medicine can be made to increase in the local deposits of nasal cavity, and cause that the clearance rate of mucociliary subtracts
It is slow, therefore have both the advantage of solution and gel.It is good with compliance easy to use, patient, with agents area after administration
Affinity is strong, the holdup time is long, drug release is slow, can improve the advantage of the bioavilability of medicine.U.S. FDA and China SFDA are
Have approved various situ-gel products, the ophthalmically acceptable ion-sensitive type instant-type gel of such as metipranolol, Ketotifen Fumarate nose is with being
Type gel etc., but have not yet to see the report of the nasal in-situ gel that relevant menthol is main ingredient.
The present invention includes preservative, infiltration by menthol, environmental sensitivity hydrophilic gel matrix and other pharmaceutic adjuvants
Pressure conditioning agent and/or NMF are made.Said preparation is at room temperature liquid, at nasal cavity position because of local temperature, ion
The change of intensity or pH value and there is phase in version and form semi-solid or solid pharmaceutical preparation, had both the advantage of solution and gel,
With, the holdup time strong with agents area affinity be long, slow drug release after easy to use, administration, the biological utilisation of medicine is improved
Degree and the advantages of without nasal ciliary toxicity.This preparation can be used for plateau or dry environment nasal cavity moistening, dry particular surroundings nasal cavity
The preventing and treating of protection, rhinitis sicca and nosebleed.
The content of the invention
Regarding to the issue above, it is a primary object of the present invention to provide a kind of nasal cavity situ-gel with menthol as main ingredient
Preparation and preparation method thereof.Suitable quantity of water is swollen in by environmental sensitivity hydrophilic gel host material heating fully dissolving or in low temperature
Middle formation gel solution, adds after menthol is mixed with solubilizer and after being fully ground and be thoroughly mixed in gel solution,
The include but is not limited to NMF, preservative for adding formula ratio uniformly mix, and the constant volume that adds water is filling.To reach above-mentioned purpose,
The present invention provides following solution technical scheme：The main component of the situ-gel with phase in version property that the present invention is provided is thin
Auxiliary material is commonly used on lotus brain and environmental sensitivity hydrophilic gel host material and other pharmacies, auxiliary material is commonly used in the pharmacy
Including but not limited to solubilizer, NMF, preservative etc..The composition of preparation is：Menthol quality volume fraction is 0.05%-
3%, environmental sensitivity hydrophilic gel substrate material quality volume fraction is 1%-30%, acceptable medicinal in other pharmacies
Auxiliary material quality volume fraction is 5%-25%, balance of water.The composition of preferred preparation is：Menthol quality volume fraction is
0.05%-2%, environmental sensitivity hydrophilic gel substrate material quality volume fraction is 1%-20%, can be connect in other pharmacies
The pharmaceutic adjuvant quality volume fraction received is 5%-20%, balance of water.
Acceptable pharmaceutic adjuvant includes but is not limited to quality volume fraction and does not surpass in other pharmacies of the present invention
Cross 1% preservative, quality volume fraction and be no more than 15% NMF and/or solubilizer.Described solubilizer is selected from poly- second two
One or more in alcohol 600, PEG400, polyethylene glycol 200, Tween 80, polysorbas20, propane diols, glycerine；Described
Preservative is selected from benzoic acid, sorbic acid, eucalyptus oil, perilla herb oil, PVP-I, chlorhexidine acetate, benzalkonium bromide, phenoxy group second
In alcohol, cloth rhodols, triclosan, hydantoin, imidazolidinyl urea, methyl hydroxybenzoate, ethylparaben and propylben
One or more；Described NMF is selected from hyaluronic acid, 1,3-BDO, sorbierite, propane diols, glycerine, polyethylene glycol
400th, one or more in Macrogol 600.
Mentholated nasal in situ gel preparation of the present invention, is free-flowing under room temperature and storing state
Liquid condition, forms the gel of semi-solid or solid state, it is characterised in that select under environment in nasal cavity effect after nasal-cavity administration
The material of environment sensitive hydrophilic gel be acceptable gelatinizing agent in pharmacy, selected from deacetylated gellan gum, Carbomer 910,
In carbomer 934, Acritamer 940, carbomer934, PLURONICS F87 and poloxamer188, sodium alginate and shitosan
One or more mixture.
Another object of the present invention is to solve the problems, such as menthol slightly water-soluble, there is provided a kind of menthol is the nose of main ingredient
Its preparation method of chamber in-situ gel preparation.After first by the menthol of recipe quantity and solubilizer ground and mixed, then slowly add
In the material aqueous solution of the environment sensitive hydrophilic gel for entering to swell in the formation of suitable quantity of water, after being sufficiently mixed uniformly, place is added
The preservative and/or NMF of side's amount, add water constant volume, is well mixed, the filling spray nose bottle in nasal drip bottle or with atomizing pump
In.
Acceptable pharmaceutic adjuvant includes but is not limited to solubilizer, NMF, increasing in other pharmacies of the present invention
Thick dose, preservative, osmotic pressure regulator, plasticizer, pH adjusting agent, aromatic etc., the wherein preferred Hydroxypropyl methylcellulose of thickener
And sodium carboxymethylcellulose.
Nasal cavity in-situ gel preparation with menthol as main ingredient of the invention can be used for plateau or dry environment nasal cavity moistening,
Dry the preventing and treating of protection, rhinitis sicca and the nosebleed of particular surroundings nasal cavity.
Advantages of the present invention has compliance easy to use, patient good, strong with agents area affinity after administration, when being detained
Between long, drug release it is slow, be conducive to improving the bioavilability of medicine and without nasal ciliary toxicity.
Specific embodiment
Present pre-ferred embodiments are given with reference to specific embodiment, to describe technical scheme in detail, but
These embodiments do not constitute any limitation to the present invention.
Embodiment 1
Pharmaceutical formulation and preparation method：
Preparation method：PLURONICS F87, the HPMC K4M of recipe quantity are weighed, the deionization of 500mL is added
Water, heating is completely dissolved into the material aqueous solution of environment sensitive hydrophilic gel in 90 DEG C of water-baths, by the menthol of recipe quantity, tells
The mixing of temperature -80 is sufficiently stirred for mixing in being transferred to the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, then
The Macrogol 600 of addition recipe quantity, glucose, Bronopol make dissolving fully mix, plus deionized water is to total amount, is sub-packed in
In spray nose bottle in nasal drip bottle or with atomizing pump, obtain final product.
Embodiment 2
Pharmaceutical formulation and preparation method：
Preparation method：Deacetylated gellan gum, the Carbomer 910 of recipe quantity are weighed, the deionized water of 800mL is added, 90
Heating is completely dissolved into the material aqueous solution of environment sensitive hydrophilic gel in DEG C water-bath, by the menthol and polyethylene glycol of recipe quantity
400th, Macrogol 600 mixing is transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, then is added
Enter hyaluronic acid, glucose, the chlorhexidine acetate of recipe quantity, dissolving is fully mixed, plus deionized water is to total amount, is sub-packed in drop
In spray nose bottle in nose bottle or with atomizing pump, obtain final product.
Embodiment 3
Pharmaceutical formulation and preparation method：
Preparation method：Poloxamer188, the Acritamer 940 of recipe quantity are weighed, adds the deionized water concussion of 650mL mixed
Close, in 4 DEG C of refrigerator refrigerated overnight make its it is fully swelling form uniform clear and bright gel solution, by the menthol of recipe quantity with
PEG400 mixing is transferred in above-mentioned gel solution after being fully ground, and is added the Macrogol 600 of recipe quantity, benzene and is pricked
Bromine ammonium, benzoic acid make dissolving fully mix, plus deionized water is sub-packed in the spray nose bottle in nasal drip bottle or with atomizing pump to total amount
In, obtain final product.
Embodiment 4
Pharmaceutical formulation and preparation method：
Preparation method：The deionized water that the deacetylated gellan gum of recipe quantity, sodium alginate add 600mL is weighed, at 90 DEG C
Heating is completely dissolved into the material aqueous solution of environment sensitive hydrophilic gel in water-bath, the menthol of recipe quantity is mixed with glycerine and is filled
It is transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after dividing grinding, adds sorbierite, the Ni Bo of recipe quantity
Tortoise beetle ester makes dissolving shake mixing, plus deionized water is sub-packed in the spray nose bottle in nasal drip bottle or with atomizing pump, i.e., to total amount
.
Embodiment 5
Pharmaceutical formulation and preparation method：
Preparation method：Poloxamer188, PLURONICS F87, the HPMC K4M of recipe quantity are weighed, is added
The deionized water concussion mixing of 600mL, refrigerated overnight makes its fully swelling uniform clear and bright gel of formation molten in 4 DEG C of refrigerator
Liquid, by the menthol of recipe quantity and Tween 80, mix be fully ground after be transferred in above-mentioned gel solution, add recipe quantity
Glucose, Macrogol 600, PVP-I, make dissolving fully mix, plus deionized water is to total amount, be sub-packed in nasal drip bottle or
In spray nose bottle with atomizing pump, obtain final product.
Embodiment 6
Pharmaceutical formulation and preparation method：
Preparation method：The deacetylated gellan gum and carbomer 934 of recipe quantity are weighed, the deionized water concussion of 600mL is added
Mixing, refrigerated overnight makes its fully swelling uniform clear and bright gel solution of formation in 4 DEG C of refrigerator, by the menthol of recipe quantity
In mixing the material aqueous solution of the environment sensitive hydrophilic gel for being transferred to above-mentioned after being fully ground with Tween 80, polysorbas20 glycerine,
PEG400, glucose, the sorbic acid for adding recipe quantity are fully mixed and make dissolving, plus deionized water is to total amount, is sub-packed in
In spray nose bottle in nasal drip bottle or with atomizing pump, obtain final product.
Embodiment 7
Pharmaceutical formulation and preparation method：
Preparation method：The Acritamer 940 and deacetylated gellan gum of recipe quantity are weighed, the deionized water mixing of 800mL is added,
In 4 DEG C of refrigerator refrigerated overnight make its it is fully swelling form uniform clear and bright gel solution, by the menthol of recipe quantity with tell
The mixing of temperature 80 is transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, and adds the saturating of recipe quantity
Bright matter acid, glucose, imidazolidinyl urea, fully mixing makes dissolving, plus deionized water to total amount, is sub-packed in nasal drip bottle or carries
In the spray nose bottle of atomizing pump, obtain final product.
Embodiment 8
Pharmaceutical formulation and preparation method：
Preparation method：PLURONICS F87, the deacetylated gellan gum of recipe quantity are weighed, adds the deionized water of 750mL to mix
Close, in 4 DEG C of refrigerator refrigerated overnight make its it is fully swelling form uniform clear and bright gel solution, by the menthol of recipe quantity with
Tween 80 mixing is transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, and is added recipe quantity and is gathered
Ethylene glycol 600, mannitol, methyl hydroxybenzoate, ethylparaben, fully mixing makes dissolving, plus deionized water to total amount, is sub-packed in
In spray nose bottle in nasal drip bottle or with atomizing pump, obtain final product.
Embodiment 9
Pharmaceutical formulation and preparation method：
Preparation method：Deacetylated gellan gum, carbomer934, the carbomer 934 of recipe quantity are weighed, going for 850mL is added
Ionized water mixes, and refrigerated overnight makes its fully swelling uniform clear and bright gel solution of formation in 4 DEG C of refrigerator, by recipe quantity
Menthol mix with Tween 80 be fully ground after be transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel, add
The 1,3-BDO of recipe quantity, methyl hydroxybenzoate, ethylparaben, fully mixing makes dissolving, plus deionized water is to total amount, dispenses
In spray nose bottle in nasal drip bottle or with atomizing pump, obtain final product.
Embodiment 10
Pharmaceutical formulation and preparation method：
Preparation method：The Carbomer 910 of recipe quantity is weighed, the deionized water mixing of 850mL is added, in 4 DEG C of refrigerator
Refrigerated overnight makes its fully swelling uniform clear and bright gel solution of formation, and the menthol of recipe quantity is mixed with PEG400
It is transferred to after being fully ground in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel, adds glycerine, the purple perilla of recipe quantity
Oil, eucalyptus oil, fully shaking is mixed makes dissolving, plus deionized water to total amount, is sub-packed in nasal drip bottle or the spray with atomizing pump
In nose bottle, obtain final product.
Embodiment 11
Pharmaceutical formulation and preparation method：
Preparation method：The Carbomer 910 and Acritamer 940 of recipe quantity are weighed, the deionized water mixing of 800mL is added, 4
DEG C refrigerator in refrigerated overnight make its it is fully swelling form uniform clear and bright gel solution, by the menthol of recipe quantity and poly- second two
The mixing of alcohol 400 is transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, and adds recipe quantity
Hyaluronic acid, mannitol, phenoxetol are fully mixed makes dissolving, plus deionized water is to total amount, is sub-packed in nasal drip bottle or band
Have in the spray nose bottle of atomizing pump, obtain final product.
Embodiment 12
Pharmaceutical formulation and preparation method：
Preparation method：PLURONICS F87, the deacetylated gellan gum of recipe quantity are weighed, adds the deionized water of 750mL to mix
Close, refrigerated overnight makes its fully swelling uniform clear and bright solution of formation in 4 DEG C of refrigerator, by the menthol and tween of recipe quantity
80 mixing are transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, and add the transparent of recipe quantity
Matter acid, mannitol, Bronopol, fully mixing makes dissolving, plus deionized water to total amount, is sub-packed in nasal drip bottle or with spraying
In the spray nose bottle of pump, obtain final product.
Embodiment 13
Pharmaceutical formulation and preparation method：
Preparation method：PLURONICS F87, the deacetylated gellan gum of recipe quantity are weighed, adds the deionized water of 750mL to mix
Close, refrigerated overnight makes its fully swelling uniform clear and bright solution of formation in 4 DEG C of refrigerator, by the menthol and tween of recipe quantity
80 mixing are transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, and add the sweet of recipe quantity
Oil, triclosan, fully mixing makes dissolving, plus deionized water is sub-packed in the spray nose bottle in nasal drip bottle or with atomizing pump to total amount
In, obtain final product.
Embodiment 14
Pharmaceutical formulation and preparation method：
Preparation method：PLURONICS F87, the deacetylated gellan gum of recipe quantity are weighed, adds the deionized water of 750mL to mix
Close, refrigerated overnight makes its fully swelling uniform clear and bright solution of formation in 4 DEG C of refrigerator, by the menthol and tween of recipe quantity
80 mixing are transferred in the material aqueous solution of above-mentioned environment sensitive hydrophilic gel after being fully ground, and add the sweet of recipe quantity
Oil, hydantoin is fully mixed makes dissolving, plus deionized water is sub-packed in the spray nose bottle in nasal drip bottle or with atomizing pump to total amount
In, obtain final product.
Embodiment 15
Pharmaceutical formulation and preparation method：
Preparation method：PLURONICS F87, the deacetylated gellan gum of recipe quantity are weighed, adds the deionized water of 750mL to mix
Close, refrigerated overnight makes its fully swelling uniform clear and bright solution of formation in 4 DEG C of refrigerator, by the menthol and tween of recipe quantity
80 mixing are stirred and evenly mixed during the material aqueous solution of above-mentioned environment sensitive hydrophilic gel is transferred to after being fully ground, and add prescription
The glycerine of amount, isothiazolyl urea, fully mixing makes dissolving, plus deionized water to total amount, is sub-packed in nasal drip bottle or with spraying
In the spray nose bottle of pump, obtain final product.
Embodiment 16
The in-situ gel preparation prepared according to embodiment 1,3,4,5,8 is with 20 μ g/kg dosage rat nasal cavities daily three
Secondary intranasal administration, continuous 7 days, be positive control with 1% deoxycholic aicd sodium solution collunarium group, and physiological saline collunarium group is normal right
According to, carry out schneiderian membrane irritant experiment, pathological section HE dyeing observations, morphology and histopathologic examination be showed no substantially with
The related irritative response of medicine and symptom.
Embodiment 17
Using in body toad maxilla cilium method, the nasal cavity in-situ gel preparation that embodiment 1,3,4,5,8 is prepared is investigated
Sample to the toxicity of schneiderian membrance cilium, by the lasting fortune of toad maxilla cilium after the treatment of observed and recorded nasal cavity in-situ gel preparation
The dynamic time, it is showed no ciliary toxicity substantially related to medicine.
Embodiment 18
The nasal cavity in-situ gel preparation sample of embodiment 1,3,4,5,8 of fluorescence labeling is determined with common focus point migration Electronic Speculum
Product find all in-situ gel preparations after 3-4h is administered in the retention time of toad maxilla cilium, still there is obvious reservation, show
Work reduces the clearance rate of nose cilium, is conducive to playing the moisture-keeping function of the hydrophilic gel.
Embodiment 19
175 Tibet Military Area Command officers and men Application Examples 8 are prepared original position by way of survey
The protection effect and applicability of gel preparation plateau nosepiece liquid are investigated.176 people, the wherein people of women 2, the people of male 174, nose
Disease illness rate is 22.16% (39/176).
1st, plateau nasal drops protection effect
The effect of this product is compared in this investigation from nasal drops to nosebleed, xeromycteria and in terms of effect effective time three.
1) to nosebleed protection effect
Notable effective 41 people (23.70%), effective 124 people (71.68%), invalid 8 people (4.62%), overall effective percentage reaches
95.38%.
2) to xeromycteria protection effect
Fine 54 people (30.86%) of effect, effective 113 people (64.57%) does not have the people of effect 8 (4.57%), is integrated with
Efficiency is up to 95.33%.
3) maintenance time is acted on
34 people (19.32%) more long, general 115 people (65.34%), shorter 27 people (15.34%).
Claims (6)
1. a kind of mentholated nasal in situ gel preparation, it includes menthol, environmental sensitivity hydrophilic gel matrix material
Material, water and acceptable pharmaceutic adjuvant in other pharmacies, wherein menthol quality volume fraction are 0.05%-3%, environment
Sensitiveness hydrophilic gel substrate material quality volume fraction is 1%-30%, acceptable pharmaceutic adjuvant quality in other pharmacies
Volume fraction is 5%-25%, balance of water.
2. mentholated nasal in situ gel preparation according to claim 1, it is characterised in that described situ-gel
Menthol quality volume fraction is 0.05%-2%, described environmental sensitivity hydrophilic gel substrate material quality volume in preparation
Fraction is 1%-20%, and acceptable pharmaceutic adjuvant quality volume fraction is 5%-20%, balance of water in other pharmacies.
3. the environmental sensitivity hydrophilic gel host material described in claim 1 is selected from deacetylated gellan gum, Carbomer 910, card
One kind in ripple nurse 934, Acritamer 940, carbomer934, PLURONICS F87, poloxamer188, sodium alginate, shitosan
Or it is various.
4. acceptable pharmaceutic adjuvant includes that quality volume fraction is no more than 1% in other pharmacies described in claim 1
Preservative, quality volume fraction are no more than 15% NMF and/or solubilizer.
5. the solubilizer described in claim 4 is selected from Macrogol 600, PEG400, polyethylene glycol 200, Tween 80, tells
Temperature 20, propane diols, glycerine；Described preservative is selected from benzoic acid, sorbic acid, eucalyptus oil, perilla herb oil, PVP-I, acetic acid chlorine
Oneself is fixed, benzalkonium bromide, phenoxetol, cloth rhodols, triclosan, hydantoin, imidazolidinyl urea, methyl hydroxybenzoate, Ni Bo
Golden ethyl ester and propylben；Described NMF is selected from hyaluronic acid, 1,3-BDO, sorbierite, propane diols, glycerine, poly-
Ethylene glycol 400, Macrogol 600.
6. the preparation method of the mentholated in-situ gel preparation described in claim 1, it is characterised in that including following preparation
Step：Formula ratio as described in claim 1, environmental sensitivity hydrophilic gel host material heating fully dissolving or molten in low temperature
It is swollen that gel solution is formed in suitable quantity of water, added after menthol is mixed with solubilizer and after being fully ground in gel solution fully
Stirring mixing, the include but is not limited to NMF, preservative for adding formula ratio uniformly mixes, and the constant volume that adds water is filling.
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| CN112791131A (en) * | 2020-12-30 | 2021-05-14 | 茂名市人民医院 | Nasal cavity cold compress gel pastes |
| CN115089563A (en) * | 2022-07-21 | 2022-09-23 | 浙江吾越生物科技有限公司 | Preparation of nasal mucosa nursing liquid dressing |
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|---|---|---|---|---|
| CN111135141A (en) * | 2020-01-20 | 2020-05-12 | 蓝佳堂生物医药（福建）有限公司 | Preparation method of composite hydrogel for nasal cavity |
| CN111297889A (en) * | 2020-02-28 | 2020-06-19 | 奥纳斯(北京)医药科技有限公司 | A composition for inhibiting gastrointestinal spasm and biliary system spasm, its aqueous solution and its preparation method |
| CN112791131A (en) * | 2020-12-30 | 2021-05-14 | 茂名市人民医院 | Nasal cavity cold compress gel pastes |
| CN112791131B (en) * | 2020-12-30 | 2023-03-10 | 茂名市人民医院 | Nasal cavity cold compress gel pastes |
| CN116887849A (en) * | 2021-09-27 | 2023-10-13 | 江西济民可信集团有限公司 | Huangshi sound spray and preparation method and application thereof |
| CN115089563A (en) * | 2022-07-21 | 2022-09-23 | 浙江吾越生物科技有限公司 | Preparation of nasal mucosa nursing liquid dressing |
| CN117919302A (en) * | 2023-12-29 | 2024-04-26 | 湖南天根乐微君科技有限公司 | Biological composition capable of effectively relieving rhinitis symptoms and repairing nasal mucosa as well as preparation method and application thereof |
| CN117919302B (en) * | 2023-12-29 | 2024-11-05 | 湖南天根乐微君科技有限公司 | Biological composition capable of effectively relieving rhinitis symptoms and repairing nasal mucosa as well as preparation method and application thereof |
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