CN118105330A - Compound fish-goose nasal irrigation agent, preparation method and application - Google Patents
Compound fish-goose nasal irrigation agent, preparation method and application Download PDFInfo
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- CN118105330A CN118105330A CN202311861475.5A CN202311861475A CN118105330A CN 118105330 A CN118105330 A CN 118105330A CN 202311861475 A CN202311861475 A CN 202311861475A CN 118105330 A CN118105330 A CN 118105330A
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Abstract
The invention belongs to the technical field of nasal cavity flushing medicines, and discloses a compound fish-goose nasal cavity flushing agent, a preparation method and application thereof, wherein the compound fish-goose nasal cavity flushing agent comprises 20g of centipeda minima, 15g of baical skullcap root, 12g of Chinese ephedra, 12g of cocklebur fruit, 20g of dahurian angelica root, 12g of heartleaf houttuynia herb, 10g of magnolia flower and 0.2g of borneol according to weight gram. The invention combines the modern pharmacological analysis of the medicines in the prescription, and confirms that the compound fish-goose nasal rinse has the functions of anti-inflammatory, antibacterial, antiviral, antifungal and antiallergic; the radix angelicae and the fructus xanthil are essential drugs of the nasal department of traditional Chinese medicine, have the effects of dispelling wind and eliminating dampness, penetrating muscle and striae, and relieving stuffy nose, can make the clear yang rise to the vertex, and the radix angelicae can reach the lower surface of the lung and the head and can support the spleen and stomach; xin Yixin Wen Zouqi enters the lung and helps the stomach to clear yang and ascend, dispel wind and promote the flow of nine orifices; the whole formula application can enhance the immunity of human bodies, and the nasal irrigation with the traditional Chinese medicine has great clinical treatment significance and social significance in the treatment of nasal diseases.
Description
Technical Field
The invention belongs to the technical field of nasal cavity flushing medicines, and particularly relates to a compound fish-goose nasal cavity flushing agent, a preparation method and application thereof.
Background
At present, the existing rhinitis and nasosinusitis patients can promote disease recovery by adopting nasal cavity flushing, and the existing nasal cavity flushing mostly adopts normal saline flushing, and the pure normal saline flushing only has the effects of cleaning and inhibiting bacteria and can not achieve the effects of resisting bacteria and diminishing inflammation.
The first prior art is: CN201880076209.2 powder nasal administration preparation. The present invention provides a powder nasal administration preparation containing a granular steroid hormone having an average particle diameter of 50 to 300 mu m as an active ingredient. The powder nasal administration preparation may further contain a water-soluble polymer (particularly, a water-soluble polysaccharide such as cellulose having a hydroxyalkyl group). The granular steroid hormone may comprise or be formed from testosterone and/or a derivative thereof. The water-soluble polymer may be in the form of particles. The proportion of the water-soluble polymer may be about 1 to 50 parts by weight relative to 1 part by weight of the particulate steroid hormone. The powder nasal administration preparation can be prepared by adjusting Cmax of steroid hormone to 15ng/mL or less, and can control blood concentration of steroid hormone such as testosterone in a specific range for a long time.
And the second prior art is as follows: CN 201210435340.8A Chinese medicinal preparation for nasal administration for inducing resuscitation and refreshing brain, and its preparation method are provided. The invention relates to a Chinese medicine for inducing resuscitation and restoring consciousness, and a preparation method thereof, belonging to the technical field of nasal administration preparation production, wherein the preparation comprises musk ketone extract, natural borneol, a jasminoidin extract, a curcuma longa extract and curcuma aromatica volatile oil; cosolvent: tween-80 or 1.2 propylene glycol; permeation enhancer: cyclodextrins; preservative: ethyl paraben or potassium sorbate; solvent: distilled water or water for injection; the preparation method comprises the steps of weighing natural borneol, dissolving the natural borneol by using a cosolvent, adding potassium sorbate or ethylparaben for dissolving, filtering, adding musk into the filtrate for 2 times of distillate, sequentially adding curcuma aromatica volatile oil and a penetration enhancer, stirring, adding a gardenia extract and a curcuma longa extract, stirring for 2 hours, filtering, regulating the pH to 6.0-7.0 by using a phosphate buffer solution, and finally preparing 100mL of preparation by using distilled water or water for injection. The nasal cavity administration preparation can greatly improve the efficacy of the active ingredients, has small volume, and is suitable for nasal cavity administration.
Through the above analysis, the problems and defects existing in the prior art are as follows:
(1) The prior art adopts hormone nasal cavity flushing, the hormone can not achieve antibacterial and antiviral effects, and a large amount of hormone can easily cause hormone side effects, especially for patients after nasal cavity operation, the daily flushing after operation is needed, the nasal cavity cleaning is promoted, the edema is relieved, the patients are more resistant to long-term flushing by simple hormone, and the possibility of producing the drug rhinitis is increased if the decongestant is combined.
(2) The traditional Chinese medicine preparation is used for nasal cavity flushing in the prior art, can resist inflammation and viruses, alleviate edema and avoid adhesion after nasal cavity operation, and the traditional Chinese medicine nasal cavity flushing preparation adopts musk and other medicines, has high cost price, and is difficult for patients to receive the cost.
(3) The aim and the requirements for nasal cavity irrigation are as follows: the nasal cavity edema is relieved, and the adhesion is avoided; antibacterial and antiviral, improving the micro-ecological environment of nasal cavity; can not generate drug rhinitis after long-term use. At present, no single preparation can simultaneously take the effects, and a reasonable and effective compound preparation is needed.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention provides a compound fish-goose nasal rinse, a preparation method and application.
The invention discloses a compound fish-goose nasal rinse, which consists of 20g of centipeda minima, 15g of baical skullcap root, 12g of Chinese ephedra, 12g of cocklebur fruit, 20g of dahurian angelica root, 12g of heartleaf houttuynia herb, 10g of magnolia flower and 0.2g of borneol according to the weight gram.
The invention also aims at providing a preparation method of the compound fish-goose nasal rinse, which comprises the following steps:
Sequentially weighing centipeda minima, baical skullcap root, ephedra herb, cocklebur fruit, dahurian angelica root, heartleaf houttuynia herb, magnolia flower and borneol according to a formula;
step two, decocting magnolia flower with 4 times of water for 10 minutes, and collecting water decoction to obtain magnolia flower water extract, and keeping dregs for later use;
step three, decocting the residues of centipeda minima, baical skullcap root, ephedra herb, cocklebur fruit, dahurian angelica root, heartleaf houttuynia herb and magnolia flower with 8 times of water, keeping micro-boiling for 1h, and separating out decoction when the decoction is hot; decocting the residue with 8 times of water twice, collecting decoction, filtering, concentrating the filtrate to obtain water decoction concentrate;
Step four, combining the magnolia flower water extract prepared in the step two with the water decoction concentrated solution prepared in the step three, centrifuging, and separating the supernatant to obtain a compound fish-goose nasal cavity flushing agent liquid medicine;
Step five, adding 1g of ethylparaben and 0.2g of borneol into a proper amount of 95% medicinal ethanol for dissolution, adding 6001g of polyethylene glycol, stirring for dissolution, and adding into the compound fish-goose nasal rinse liquid medicine after uniform mixing; adding purified water to 1000mL, stirring, placing in a sterilizing container, and sterilizing with circulating steam to obtain the compound fish goose nasal rinse.
Further, the preparation method of the magnolia flower water extract in the second step comprises the following steps: the preparation method of the magnolia flower water extract comprises the following steps: decocting flos Magnoliae with 4 times of water, keeping boiling for 10 min, and filtering to obtain flos Magnoliae water extract.
In the third step, water which is 3 to 6 times of the weight of the medicine materials is added for the first time.
Further, in the third step, the filtrate was concentrated to a density of 1.33g/mL.
Further, the centrifugation conditions in step four are: centrifuging at 4000-5500 r/min for 5-15 min.
Further, the circulating steam sterilization time in the fifth step is 40-60 min.
Further, in the fifth step, the compound fish-goose nasal rinse agent is placed in a sterilization container for circulating steam sterilization, which comprises the following steps:
(1) Placing the compound fish-goose nasal rinse agent with the constant volume in a sterilization container in a circulating steam sterilization cabinet;
(2) Introducing water vapor into the circulating water vapor sterilization cabinet for high-temperature short-time treatment;
(3) And taking out when the pressure in the circulating steam sterilization cabinet is reduced to zero, cooling in a clean room, and packaging to obtain the compound fish-goose nasal rinse.
Further, the temperature at which the high-temperature short-time treatment starts to time in the step (2) is 90 to 110 ℃, and the internal pressure at which the high-temperature short-time treatment starts to time is 0.12 to 0.15Mpa.
The invention also aims at providing a method for implementing the compound fish-goose nasal rinse, which comprises the following steps:
performing nasal cavity flushing by using 200mL of the compound fish-goose nasal cavity flushing agent;
is suitable for adults 1-2 times per day.
The invention further aims at providing the anti-inflammatory detumescence nasal cavity cleaning medicine, which comprises the compound fish-goose nasal cavity washing agent.
In combination with the technical scheme and the technical problems to be solved, the technical scheme to be protected has the following advantages and positive effects:
Firstly, at present, no reliable and effective traditional Chinese medicine nasal irrigation agent which can be widely popularized and used exists in clinic, and hormone or normal saline is mostly adopted for nasal irrigation, and then medicines such as traditional Chinese medicine ointment and the like are additionally added for nasal rubbing or hormone nasal spraying and the like, so that the treatment procedures are increased, and the treatment cost is increased. If the simple and effective traditional Chinese medicine nasal cavity flushing liquid can be popularized and used, the mode of flushing and nasal cavity medication can be replaced simultaneously by a simple method of flushing the traditional Chinese medicine nasal cavity, so that the time and cost of a patient are greatly saved, and the traditional Chinese medicine nasal cavity flushing liquid has great clinical treatment significance and social significance in the treatment of nasal diseases.
Meanwhile, the existing clinical flushing agent finished products are mainly normal saline, the effect of the flushing agent is only cleaning and bacteriostasis, nasal cavity flushing is carried out through a traditional Chinese medicine compound, physical effect of nasal cavity flushing can be achieved, secretion in nasal cavities is promoted to be removed, the purposes of anti-inflammation and antivirus are achieved after the nasal cavity mucosa locally absorbs traditional Chinese medicine, nasal cavity edema is further reduced, adhesion and other conditions are avoided, the traditional Chinese medicine nasal cavity flushing can also avoid conditions of shrinkage and dryness of the nasal mucosa and the like caused by long-term use of hormone, even the nasal mucosa which is dried can be improved, and nasal bleeding caused by nasal cavity drying of a patient is avoided. Because nasal cavity irrigation directly acts on the disease area, the drug concentration reduction caused by the first pass effect of the liver is avoided, and the occurrence of systemic side effects is also avoided. At present, no normal and systematic traditional Chinese medicine compound nasal cavity flushing agent exists clinically, so that the application value and the commercial value prospect of the effective, simple and convenient traditional Chinese medicine nasal cavity flushing agent are considerable.
The compound fish goose nasal irrigation has the advantages of normal saline nasal irrigation, and simultaneously, the traditional Chinese medicine can resist inflammation, resist virus and relieve edema due to the addition of the traditional Chinese medicine, so that the adhesion after nasal operation is avoided, and the traditional Chinese medicine nasal irrigation is clinically carried out by adopting the preparation at present, and no side effect is generated at present. Therefore, the compound fish and goose washing agent with anti-inflammatory and antiviral treatment effects has higher clinical diagnosis and treatment advantages, adopts common medicines, has no precious medicines, is low in cost, and is easier to occupy a place in the aspect of the huge commercial market of the nasal washing agent in the future.
The traditional Chinese medicine nasal irrigation agent adopted by the invention has no definite prescription for nasal irrigation in clinic, so the invention belongs to the technical blank in the aspect of nasal irrigation medication. The nasal cavity administration method for treating nasal or systemic diseases is ancient, wu Shiji 'Li yue' is used for treating nasal and twelve channels, so that the method for treating rhinitis by using the Chinese medicine nasal cavity irrigation is safe and effective. In the early clinical application observation, the compound fish goose nasal cavity flushing agent is adopted to treat rhinitis, compared with single physiological saline or hormone and decongestant treatment, the symptom is relieved more obviously and rapidly, no toxic or side effect occurs, and the recurrence rate after stopping the drug is lower. The compound fish-goose nasal rinse agent also has no local or systemic toxic and side effects such as atrophic rhinitis, dry rhinitis and the like.
By combining modern pharmacological analysis of the medicine in the prescription, the compound fish-goose nasal irrigation has the effects of anti-inflammatory, antibacterial, antiviral, antifungal and antiallergic, wherein the radix angelicae and the fructus xanthil are essential medicines in the nasal department of traditional Chinese medicine, have the effects of dispelling wind and eliminating dampness, penetrating muscle and skin striae and opening orifices, can make clear yang rise to peak, and can reach the position below the head of the lung and the defend face to support the spleen and the stomach; xin Yixin Wen Zouqi the lung and stomach are nourished, and the clear yang is upward moved, so that the wind is dispersed and the nine orifices are cleared. The whole formula is applied, the synergistic effect is enhanced, the absorption speed of the medicine is increased, and the immunity of a human body can be enhanced.
Secondly, the traditional Chinese medicine nasal cavity flushing agent adopted by the invention belongs to the technical blank in the aspect of traditional Chinese medicine nasal cavity flushing and medication in the industry. The invention adopts the compound Chinese medicine fish and goose nasal cavity to wash, can achieve the effects of anti-inflammatory, detumescence, antivirus and the like on the basis of nasal cavity cleaning, and can completely replace physiological saline nasal cavity to wash in the aspect of treating nasal cavity inflammation.
The invention adopts the Chinese herbal compound fish-goose nasal cavity to wash, not only can play a role of resisting inflammatory viruses because of local absorption of nasal mucosa, but also can enhance the whole body immunity of a human body through the local absorption of Chinese herbal medicine in the nasal cavity because of the dialectical idea of the traditional Chinese medicine, thereby achieving the aim of avoiding repeated attacks of diseases, and being the advantage which cannot be achieved by pure normal saline, hormone and decongestant.
Third, each claim of the present invention adds specific technical features to the method or product.
The following is an analysis of the significant technical advances made by each claim:
1. The invention describes a preparation method of a compound fish-goose nasal rinse, which comprises the operation details of each step. This is the core step in the preparation of such a rinse.
3. The invention describes the water extraction method of the magnolia flower in the step one in detail, and adds two extraction and precipitation processes to obtain the magnolia flower water extract, which is helpful for improving the extraction efficiency and purity of the magnolia flower.
4. The water extraction method of magnolia flower of the present invention specifies specific operating conditions such as extraction temperature, time, precipitation temperature and time, etc., which help to ensure the effectiveness and stability of the extraction.
5. The preparation method of the present invention specifies more specific operation conditions such as the ratio of the decocted medicinal material and water, the concentration degree of the filtrate, the condition of centrifugation and the time of steam sterilization, which helps to optimize the preparation process and ensure the quality of the product.
6. The invention increases the use of sterilizing container and cabinet in the process of circulating steam sterilization, and ensures the sterility and safety of the product.
7. The steam-through sterilization process of the present invention specifies specific operating conditions, such as temperature and internal pressure, which help ensure the effectiveness of sterilization and stability of the product.
The formula and the preparation method of the compound fish-goose nasal irrigation agent increase specific technical characteristics and operation conditions, thereby bringing about remarkable technical progress. The technical characteristics and the operating conditions help to improve the effect, stability and safety of the product, so that the product is more suitable for being used as a nasal rinse.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments of the present invention will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a flowchart of a preparation method of the compound fish-goose nasal rinse agent provided by the embodiment of the invention;
FIG. 2 (a) is a single-factor investigation HPLC chart of the soaking time of the mixed reference substance provided by the embodiment of the invention;
FIG. 2 (b) is a single factor view HPLC chart of soaking for 0h provided by the examples of the present invention;
FIG. 2 (c) is a single factor review HPLC chart for 1h of soak provided by the examples of the present invention; ;
FIG. 2 (d) is a single factor review HPLC plot of soaking for 2h provided by the examples of the present invention; ;
FIG. 3 (a) is an orthogonal experimental HPLC diagram of a mixed control provided by an embodiment of the present invention;
FIG. 3 (b) is an HPLC chart of orthogonal experiment 1 provided by the example of the present invention;
FIG. 3 (c) is an HPLC chart of orthogonal experiment 2 provided by the example of the present invention;
FIG. 3 (d) is an HPLC chart of orthogonal experiment 3 provided by the example of the present invention;
FIG. 3 (e) is an HPLC chart of orthogonal experiment 4 provided by the example of the present invention;
FIG. 3 (f) is an HPLC chart of orthogonal experiment 5 provided by the example of the present invention;
FIG. 3 (g) is an HPLC chart of orthogonal experiment 6 provided by the example of the present invention;
FIG. 3 (h) is an HPLC chart of orthogonal experiment 7 provided by the example of the present invention;
FIG. 3 (i) is an HPLC chart of orthogonal experiment 8 provided by an embodiment of the present invention;
FIG. 3 (j) is an HPLC chart of orthogonal experiment 9 provided by an embodiment of the present invention;
FIGS. 4 (a) - (f) are graphs of experimental HPLC for optimal process comparison and verification provided by the examples of the present invention;
FIGS. 4 (g) - (l) are comparative and validated experimental HPLC plots for comparative processes provided in examples of the present invention;
FIG. 5 (a) is a schematic diagram of a process for removing precipitation of mixed ephedrine hydrochloride pseudoephedrine hydrochloride;
fig. 5 (b) is a schematic diagram of a precipitation removal process of the compound fish-goose nasal rinse (liquid a) provided by the embodiment of the invention;
fig. 5 (c) is a process diagram before removing precipitation of the compound fish-goose nasal rinse (liquid B) provided by the embodiment of the invention;
FIG. 6 is a schematic diagram showing the effect (HE, x 200) of a compound fish goose nasal rinse of a blank control group, a model group and a triamcinolone acetonide group on pathological changes of nasal mucosa of a model rat according to an embodiment of the present invention;
FIG. 7 shows the effect of the compound fish goose nasal irrigation agent provided by the embodiment of the invention on PCT, IL-6 protein expression in nasal mucosa tissue of model mice.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Aiming at the problems existing in the prior art, the invention provides a compound fish-goose nasal rinse, a preparation method and application, and the invention is described in detail below with reference to the accompanying drawings.
The numerical ranges of the components of the compound fish goose nasal irrigation agent can be estimated based on the reference numerical values. The compatibility of the Chinese herbal medicines can be adjusted within a certain range to adapt to different requirements and drug effects.
1. Centipeda minima: 18-22g
2. Radix Scutellariae Baicalensis: 13-17g
3. Herba Ephedrae: 10-14g
4. Fructus Xanthii: 10-14g
5. Radix angelicae: 18-22g
6. Cordate houttuynia: 10-14g
7. Flos Magnoliae: 8-12g
8. Borneol: 0.15-0.25g.
With the basic concept unchanged, the components can be appropriately adjusted or replaced to form six different component versions. The following are six analogous components of the extension: 1) Compound fish and goose nasal irrigation agent A:
Centipeda minima 18g
Radix Scutellariae 14g
Herba Ephedrae 10g
Fructus Xanthii 14g
Radix Angelicae Dahuricae 22g
Houttuynia cordata 10g
Flos Magnoliae 12g
Borneol 0.3g.
2) Compound fish and goose nasal irrigation agent B:
20g of honeysuckle (replacing centipeda) and 13g of baical skullcap root
Ephedra herb 12g
Fructus Xanthii 10g
Radix Angelicae Dahuricae 18g
Houttuynia cordata 14g
Flos Magnoliae 10g
Borneol 0.25g.
3) Compound fish and goose nasal irrigation agent C:
Centipeda minima 19g
Radix Scutellariae 15g
Cyrtomium fortunei 10g (instead of ephedra)
Fructus Xanthii 13g
21G of dahurian angelica root
Houttuynia cordata 11g
Flos Magnoliae 11g
Borneol 0.15g.
4) Compound fish and goose nasal irrigation agent D:
centipeda minima 17g
Chinese angelica 15g (instead of baikal skullcap root)
Ephedra herb 14g
Fructus Xanthii 12g
20G of dahurian angelica root
Houttuynia cordata 12g
Flos Magnoliae 12g
Borneol 0.1g.
5) Compound fish and goose nasal irrigation agent E:
centipeda minima 20g
Baical skullcap root 13g
Ephedra herb 11g
Fructus Xanthii 12g
Radix Angelicae Dahuricae 18g
Mulberry leaf 15g (replacing cordate houttuynia)
Flos Magnoliae 12g
Borneol 0.2g.
6) Compound fish goose nasal irrigation agent F:
centipeda minima 20g
Radix Scutellariae 15g
Ephedra herb 12g
Glycyrrhrizae radix 10g (instead of fructus Xanthii)
20G of dahurian angelica root
Houttuynia cordata 12g
Flos Magnoliae 10g
Borneol 0.2g.
Each formulation has its unique efficacy and can help to address different nasal problems. The replacement or adjustment of these components is based on the traditional application and function of the herbs, but prior to actual application, clinical tests are preferably performed to verify their safety and effectiveness.
The compound fish-goose nasal cavity washing agent provided by the embodiment of the invention comprises 20g of centipeda minima, 15g of radix scutellariae, 12g of ephedra, 12g of fructus xanthil, 20g of radix angelicae, 12g of cordate houttuynia, 10g of magnolia flower and 0.2g of borneol according to the weight gram.
As shown in fig. 1, the preparation method of the compound fish goose nasal rinse provided by the embodiment of the invention comprises the following steps:
S101, sequentially weighing herba Centipedae, radix Scutellariae, herba Ephedrae, fructus Xanthii, radix Angelicae Dahuricae, herba Houttuyniae, flos Magnoliae and Borneolum Syntheticum according to a formula;
S102, decocting flos Magnoliae with 4 times of water for 10 minutes, and collecting water decoction to obtain flos Magnoliae water extract, and keeping the residue;
S103, decocting herba Centipedae, radix Scutellariae, herba Ephedrae, fructus Xanthii, radix Angelicae Dahuricae, herba Houttuyniae and flos Magnoliae residues with 8 times of water, keeping micro-boiling for 1 hr, and separating out decoction when it is hot; decocting the residues with 8 times of water twice, collecting decoction, filtering, concentrating the filtrate to obtain water decoction concentrate;
s104, combining the magnolia flower water extract prepared in the step S102 with the water decoction concentrated solution prepared in the step S103, centrifuging, and separating the supernatant to obtain a compound fish goose nasal cavity flushing agent liquid;
S105, adding 1g of ethylparaben and 0.2g of borneol into a proper amount of 95% medicinal ethanol for dissolution, adding 6001g of polyethylene glycol, stirring for dissolution, and adding into the compound fish-goose nasal rinse liquid medicine after uniform mixing; adding purified water to 1000mL, stirring, placing in a sterilizing container, and sterilizing with circulating steam to obtain the compound fish goose nasal rinse.
The preparation method of the magnolia flower water extract in the step S102 provided by the embodiment of the invention comprises the following steps: the preparation method of the magnolia flower water extract comprises the following steps: decocting flos Magnoliae with 4 times of water, keeping boiling for 10min, and filtering to obtain flos Magnoliae water extract.
In the step S103 provided by the embodiment of the invention, water with the weight 3-6 times of that of the medicine materials is added for the first time, and the filtrate is concentrated to the density of 1.33g/mL.
The centrifugation conditions in step S104 provided by the embodiment of the present invention are: centrifuging at 4000-5500 r/min for 5-15 min.
The circulating steam sterilization time in the step S105 provided by the embodiment of the invention is 40-60 min.
In step S105 provided by the embodiment of the present invention, the method for performing steam sterilization by placing the compound fish goose nasal rinse agent in a sterilization container includes:
(1) Placing the compound fish-goose nasal rinse agent with the constant volume in a sterilization container in a circulating steam sterilization cabinet;
(2) Introducing water vapor into the circulating water vapor sterilization cabinet for high-temperature short-time treatment;
(3) And taking out when the pressure in the circulating steam sterilization cabinet is reduced to zero, cooling in a clean room, and packaging to obtain the compound fish-goose nasal rinse.
The temperature for starting the high-temperature short-time treatment in the step (2) provided by the embodiment of the invention is 90-110 ℃, and the internal pressure for starting the high-temperature short-time treatment is 0.12-0.15 Mpa.
The application method of the compound fish-goose nasal rinse provided by the embodiment of the invention comprises the following steps:
performing nasal cavity flushing by using 200mL of the compound fish-goose nasal cavity flushing agent;
is suitable for adults 1-2 times per day.
The technical effects of the present invention will be further described with reference to pharmacological analysis.
Centipeda minima is derived from edible Ben Cao (edible Ben Cao), pungent and warm. It enters lung and liver meridians. Disperse wind-cold, relieve stuffy nose, relieve cough and detoxify. "Centipeda shall be used to treat headache and eye diseases, and to treat common cold, nasal qi and meat polyp" in Ben Cao gang mu. It has the actions of "freeing nasal orifices and benefiting nine orifices" directly in Jiayou Ben Cao. Modern pharmacological researches show that the centipeda minima has the effects of resisting inflammation, allergy, mutagenesis, bacteria and antigen organisms, and the contained pseudo-guaiacolide has the effects of resisting bifidobacteria, staphylococcus aureus and bacillus subtilis.
The name of houttuynia cordata is Ming Yi Bie Lu. Enter bladder meridian, lung meridian and large intestine meridian. The herb can expel pus and cure carbuncles; clearing heat and detoxicating; induce diuresis to treat stranguria. The cordate houttuynia decoction has inhibiting effect on pneumococcus, staphylococcus aureus, tubercle bacillus, etc., and can promote phagocytic capacity of macrophage and leucocyte obviously and has obvious anti-inflammatory effect. In vitro antibacterial experiments show that houttuynin has obvious inhibition effect on staphylococcus aureus, moraxella catarrhalis, streptococcus pneumoniae and haemophilus influenzae. The antibacterial effect of the herba houttuyniae volatile oil is observed by a liquid method and a solid method. The results show that the composition has strong antibacterial effect on the sarcina and staphylococcus aureus, and has certain antibacterial effect on streptococcus pneumoniae and beta-hemolytic streptococcus.
Fructus Xanthii, also known as lice of cattle, is bitter in taste, sweet, pungent and warm in Guizhou folk prescription drug set; small toxicity, entering the lung and liver meridians. Function to unblock nose; dispelling wind-cold; relieving itching; dispelling wind-dampness. In the book of herbal preparation, it is well documented that it can treat nasosinusitis and other diseases, such as sweating, wind-damp-dispelling, upper brain-top-dredging, lower foot and knee-joint-descending and skin-external. For treating nasosinusitis, headache, dark eyes, odontalgia and thorsis, experimental researches show that the decoction has an inhibiting effect on partial fungi and bacteria, and clinical reports indicate that the decoction has good effects for treating diseases such as local acute inflammation.
Xin Yixing pungent and warm, enter lung and stomach meridians. Can relieve nasal obstruction and dispel wind-cold. It is explicitly recorded in "Yunnan Bencao" to treat brain leakage, nasosinusitis, dispel wind and bake new tile into powder. For cold pain in face, pain in stomach qi, and hot sprinkled. But the medicinal method is recorded in Ben Cao gang mu. The nasal ulcer, the allergic rhinitis, the nasal choking, the nasal sore and the post-acne nasal sore are ground into powder, and a small amount of musk is added, and the fistular onion stalk is dipped for a plurality of times. Modern pharmacological research shows that the volatile oil can promote the absorption of mucous secretion and reduce inflammation, and has the function of constricting nasal mucosa blood vessels; meanwhile, the water or alcohol extract has better antiallergic effect, and the water or alcohol extract has inhibition effect on various pathogenic bacteria, thus being a better mucosa vasoconstriction medicament.
The radix scutellariae is recorded in Shennong's herbal channels at the earliest time, has obvious effects of cooling blood, clearing heat, detoxifying and the like, enters lung, heart liver and large intestine channels, has the effects of resisting fatigue, resisting bacteria and viruses, resisting inflammation and resisting allergic reaction, has good effect of enhancing organism immunity, and baicalin and baicalein in the radix scutellariae can improve the permeability of capillaries of patients and relieve the inflammatory reaction exudation swelling condition of patients; the baikal skullcap root also has anti-tumor effect, and can inhibit tumor proliferation, growth and other mechanisms. Radix Scutellariae is a common herb in clinical antiviral formulations. A large number of clinical and network pharmacological studies also show that the prescription containing the baical skullcap root has remarkable antiviral effect.
The angelica dahurica is derived from the root of perennial herb angelica dahurica or angelica dahurica of the Umbelliferae, has warm nature, aromatic smell, pungent taste and slight bitter taste, has the effects of dispelling wind and removing dampness, inducing resuscitation and relieving pain, and relieving swelling and expelling pus, is clinically and widely applied to symptoms such as common cold headache, glabrous bone pain, nasal obstruction, nasosinusitis, toothache, leucorrhea, sore pain of sores and the like, and has better curative effect. The angelica dahurica has: 1) Promoting blood circulation, removing blood stasis, and relieving spasm: the angelica dahurica has the effects of dilating arterial blood vessels, accelerating blood flow, changing blood properties and relieving pain, and has obvious curative effect on various pains, especially on the front headache or the pain at the eyebrow. 2) Dispelling wind (cold): for wind-cold type common cold, facial paralysis and facial spasm caused by facial wind, it can also be used for treating rubella and pruritus, and is time-to-start. 3) Dehumidifying: bai Zhi is fragrant and dry in nature, so it is good at drying and eliminating dampness and treating cold-dampness with leucorrhea and Wen Chengjiu diarrhea. In addition, the angelica dahurica also has certain efficacy in the aspects of resuscitation, pus discharge, detumescence, beauty treatment and the like. Modern pharmacological researches have found that the active ingredient of dahurian angelica root has a certain absorption promoting effect on baicalin.
The application embodiment of the invention provides an anti-inflammatory detumescence nasal cavity cleaning medicament, which comprises the compound fish-goose nasal cavity flushing agent.
Examples: analysis of optimal water extraction process of compound fish-goose nasal cavity flushing agent
The method adopts an L9 (3 4) orthogonal method, takes the comprehensive score of the content of the active ingredients of ephedrine hydrochloride and pseudoephedrine hydrochloride in crude drug ephedra as an index, and under the condition of meeting the water absorption of the crude drug, three main factors influencing the decocting effect, namely the water adding amount, the decocting time and the decocting times, are not soaked, and the optimal water extraction process is analyzed.
1. Determination of Water absorption of decoction pieces
31G of decoction pieces (except flos Magnoliae and Borneolum Syntheticum) with a 1/3 times of the prescription amount are taken, soaked with 10 times of water for different times until the weight of the decoction pieces is no longer increased, and the water absorption is measured as shown in Table 1.
Table 1 investigation of water absorption of decoction pieces
As can be seen from Table 1, the water absorption of the decoction pieces was 271%, and the water absorption was 300% for convenience of operation, i.e., the water absorption of the decoction pieces was 3.0 times the weight of the medicinal material.
2. Single factor investigation of soak time
Under the condition of meeting the water absorption rate of decoction pieces, the influence of the soaking time on the content of the effective components in the prescription is inspected, the comprehensive score of the content of ephedrine hydrochloride and pseudoephedrine hydrochloride in the crude drug ephedra is taken as an inspection index, and a single factor range with the largest influence on the content is optimized.
(1) Sample preparation: taking decoction pieces (except flos Magnoliae and Borneolum Syntheticum) of 1/3 times of the prescription, adding 10 times of water, soaking for 0 hr, 1 hr, and 2 hr respectively, decocting for 3 times, 1 hr each time, filtering, mixing extractive solutions, and concentrating the liquid medicine to 50mL for use.
(2) Single factor investigation result score for soak time: the data obtained by the experiment are weighted and scored, wherein the scoring method is that the comprehensive score is composed of the content (%) of ephedrine hydrochloride in the crude drug ephedra and the content (%) of pseudoephedrine hydrochloride in the crude drug ephedra, the result is shown in table 2, the analysis of variance is shown in table 3, and the HPLC chart is shown in figure 2.
Table 2 soaking time investigation
TABLE 3 soaking time one-factor analysis of variance table
Analysis of variance of one factor shows that: p <0.05 shows that different soaking times have obvious difference, and the content of ephedrine hydrochloride and pseudoephedrine hydrochloride is highest, so that the compound water decoction and extraction are preferably carried out by adding water into the medicine materials and not soaking and boiling.
3. Orthogonal factors of the decoction process
Taking the comprehensive scores of the ephedrine hydrochloride and pseudoephedrine hydrochloride content as indexes, under the condition of meeting the water absorption rate of decoction pieces, three influencing factors of water addition quantity, decoction time and decoction times are examined, and an L9 (3 3) orthogonal table is adopted for testing, wherein the level of the orthogonal factors is shown in table 4.
TABLE 4 Water extraction Process factor level Table
(1) Sample preparation: weighing decoction pieces (except flos Magnoliae and Borneolum Syntheticum) 1/20 of the prescription, testing according to orthogonal test table (see table 4), filtering, concentrating, and fixing volume to 50mL for use.
(2) Scoring the optimized result of the water extraction process: the data obtained by the experiment are weighted and scored, wherein the scoring method is that the comprehensive score=ephedrine hydrochloride content (mg) +pseudoephedrine hydrochloride content (mg), the result is shown in table 5, the analysis of variance is shown in table 6, and the HPLC chart is shown in figure 3.
TABLE 5 Water extraction Process conditions L9 (3 3) orthogonal test arrangement and results
TABLE 6 Water extraction Process analysis of variance table
F0.05(2,2)＝19.0;F0.01(2，2)＝99.0
Analysis according to the orthogonal experimental table of the decoction process: the comprehensive score of ephedrine hydrochloride and pseudoephedrine hydrochloride content is used as an index, analysis is carried out from tables 5 and 6, the factor C has extremely significant influence, A, B has no significant influence, meanwhile, extremely bad C > B > A, C1> C2> C3, A1> A3> A2, B1> B3> B2, the optimal extraction process is determined to be A1B1C1, namely, the water amount which is 12 times of the dosage of medicinal materials is added, and the total decoction is carried out for 2 hours each time. However, analysis of variance shows that there is no significant difference between the water addition amount (a) and the decoction time (B), and considering that the A3B3C1 process (i.e., 8 times the water addition amount, 3 times each time for 1 hour) is relatively cost-effective and reduces the amount of liquid medicine to be concentrated, the best process is compared with the A3B3C1 process to determine the final water extraction process.
4. Comparison of optimal process and comparative process and verification of water extraction process
Six batches of decoction pieces with 1/3 prescription are taken, the decoction pieces are respectively extracted according to the conditions of the optimal extraction process and the quasi-contrast process (A3B 3C1 process) screened by orthogonal experiments, the comprehensive scores of the ephedrine hydrochloride and pseudoephedrine hydrochloride content are taken as indexes, whether the two processes are different or not is inspected, so as to determine the water extraction process of the preparation, the verification result is shown in table 7, the analysis of variance is shown in table 8, and the HPLC diagram is shown in figure 4.
Table 7 comparison of best process with comparative process
Table 8 analysis of variance of process comparison results
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F0.05(1,10)＝4.96,F0.01(1，10)＝10.04
Conclusion: the two water extraction processes have no statistical significance on the influence of ephedrine hydrochloride and pseudoephedrine hydrochloride content, and the A3B3C1 process (namely 8 times of water is added and each time of decoction is carried out for 1 hour and 3 times of decoction) is adopted to prepare six batches of samples. Experiments prove that the average content of ephedrine hydrochloride and pseudoephedrine hydrochloride is 13.82mg, rsd=2.61 percent, and the process is stable and feasible. Therefore, the water extraction process is determined as follows: filtering the hot water extract of flos Magnoliae to obtain medicinal liquid I. Mixing flos Magnoliae residue with the rest materials (except Borneolum Syntheticum), decocting with 8 times of water (3 times of the weight of the materials is added for the first time), keeping slightly boiling for 1 hr, separating decoction while hot, sequentially adding 8 times of water, decocting twice, mixing decoctions to obtain liquid medicine II, mixing liquid medicine I and liquid medicine II, and concentrating to obtain water decoction concentrate with a liquid-liquid ratio of 1.33 g/mL.
5. Comparison of index content before and after precipitation of compound fish-goose nasal rinse aqueous extract
(1) Taking 5mL of the finished liquid medicine of the compound fish-goose nasal rinse agent obtained according with the optimal water extraction process, centrifuging for 2min (10000 r/min), taking 1mL of supernatant, adding water to dilute to 10mL, and shaking uniformly to obtain the test liquid (liquid A) after removing the sediment.
(2) Taking 5mL of the finished medicinal liquid of the same compound fish-goose nasal rinse under the item (1), adding water to dilute to 50mL, performing ultrasonic treatment for 10min to fully extract the effective components in the finished medicinal liquid, centrifuging for 2min (10000 r/min), and separating supernatant to obtain a prepared test solution (solution B) when the precipitate of the medicinal liquid is not removed.
The content of ephedrine hydrochloride and pseudoephedrine hydrochloride in the sample is measured, the results are shown in table 9, and the HPLC chart is shown in figure 5.
Table 9 results of comparison of content of nasal rinse extract of Compound Fish goose
Conclusion: the liquid medicine is centrifuged to remove the sediment, and compared with the liquid medicine without removing the sediment, the loss of the index component content is less than 1 percent. The preparation can be considered to be firstly precipitated and removed, clear liquid is obtained, and the precipitate is reduced and the appearance of the finished product is improved on the premise of effectively maintaining the content of index components.
In summary, the optimal extraction process for determining the compound fish goose nasal rinse comprises the following steps: decocting flos Magnoliae with 4 times of water for 10min, and collecting filtrate to obtain flos Magnoliae water extractive solution, and collecting residue. Decocting herba Centipedae, scutellariae radix, herba Ephedrae, fructus Xanthii, radix Angelicae Dahuricae, herba Houttuyniae and flos Magnoliae residue with 8 times of water (3 times of water is added for the first time), keeping slightly boiling for 1 hr, separating decoction, sequentially adding 8 times of water, decocting the residue twice, collecting decoction, mixing decoctions, filtering, concentrating filtrate to density of 1.33g/mL, and obtaining water decoction concentrate. Mixing the water decoction concentrate and flos Magnoliae water extract, centrifuging for 5min (4000 rpm), and collecting supernatant to obtain compound fish-goose nasal cavity douche liquid.
6. Screening and examining of compound fish-goose nasal rinse solubilizer
Because the borneol is used in the prescription of the compound fish-goose nasal rinse, the borneol is insoluble in water, and a solubilizing agent is selected for solubilization in order to realize the dissolution of the borneol in the water extract liquid medicine. The experiment selects safe and nontoxic polyethylene glycol (PEG) series compounds to carry out solubilization investigation on borneol.
6.1 Materials
The compound fish goose nasal rinse is provided by a laboratory of the second affiliated hospital department of medicine of the Guizhou traditional Chinese medicine university.
PEG 400 (chemical purity, lot number: 20120306), PEG 600 (chemical purity, lot number: 20110727), PEG 1000 (chemical purity, lot number: 20110907), PEG 1500 (chemical purity, lot number: W201011), PEG 4000 (chemical purity, lot number: 20051105), PEG 6000 (chemical purity, lot number: 20111110), all of which were purchased from national-medicine-group chemical reagent Co.
Ethyl hydroxybenzoate, lot number 103620171201, hunan Erkang pharmaceutical Co., ltd; medicinal ethanol (95%), lot number: 20170111, jilin province, new Gekko Swinhonis, inc.; pure water.
6.2 Screening of solubilizers
Weighing 5g of each solubilizing agent, respectively placing into a 25mL measuring flask, adding medicinal ethanol to dissolve and fix volume, and preparing each solubilizing agent with concentration of 20% (g/mL), wherein other solubilizing agents except PEG 6000 can not be completely dissolved can be completely dissolved in 95% medicinal ethanol. PEG 6000 was no longer the subject of investigation for this experimental analysis due to its poor solubility in alcohol. The rest solubilizer is prepared into 20% concentration with medicinal ethanol for use.
And respectively weighing and mixing 20mg of borneol and 0.1g of ethylparaben, adding a certain amount of medicinal ethanol solution of each solubilizer with concentration of 20% to completely dissolve the borneol and the ethylparaben, and properly adjusting the dosage of the medicinal ethanol to a certain volume to obtain a medicinal ethanol solution (simply referred to as mixed ethanol solution) obtained by mixing the borneol, the ethylparaben and the solubilizer. Adding the mixed alcohol solution into 95mL of compound fish-goose nasal rinse liquid medicine for many times, stirring while adding until the liquid is basically in an equilibrium state, adding water until the final volume is 100mL, stirring uniformly, and visually observing dissolution phenomenon under sunlight. The amounts of solubilizer and medicinal ethanol in the 100mL liquid were also calculated and the results are shown in Table 10.
TABLE 10 solubilisation experimental observations
Conclusion: the above experiments show that the ideal solubilization effect is generally applicable under the conditions that the final content of the polyethylene glycol solubilizer is 0.1% and the alcohol content is 2%. Considering that the compound preparation is liquid, PEG400 and PEG600 are both liquid reagents, the compound preparation is suitable for being added into the liquid preparation, and the commercial medicinal PEG600 is cheaper than the medicinal PEG400, so that the medicinal PEG600 is selected.
Repeating the experiment for three times to verify that the compound fish-goose nasal cavity flushing agent liquid medicine of 1 preparation prescription is added with 2mL of medicinal ethanol liquid containing 6000.1g of PEG, 0.1g of ethylparaben and 0.02g of borneol, and is stirred uniformly to be in a dissolved state without obvious and visual insoluble matters being separated out.
7. Compound fish-goose nasal irrigation agent final preparation process
Screening according to experimental conditions, and setting the optimal preparation process conditions of the compound fish-goose nasal irrigation agent as follows: decocting flos Magnoliae with 4 times of water for 10min, and collecting filtrate to obtain flos Magnoliae water extractive solution, and collecting residue. Decocting herba Centipedae, scutellariae radix, herba Ephedrae, fructus Xanthii, radix Angelicae Dahuricae, herba Houttuyniae and flos Magnoliae residue with 8 times of water (3 times of water is added for the first time), keeping slightly boiling for 1 hr, separating decoction, sequentially adding 8 times of water, decocting the residue twice, filtering, concentrating filtrate to density of 1.33g/mL, and obtaining water decoction concentrate. Mixing the water decoction concentrate and flos Magnoliae water extract, centrifuging for 5min (4000 rpm), and collecting supernatant to obtain compound fish-goose extract. Adding 1g of ethylparaben and 0.2g of borneol into a proper amount of 95% medicinal ethanol for dissolution, adding 6001g of polyethylene glycol, stirring for dissolution, mixing uniformly, adding into the compound fish-goose extract, adding purified water to 1000mL, stirring uniformly, placing into a sterilization container, and sterilizing by circulating steam for 40 minutes to obtain the final compound fish-goose nasal rinse.
8. The main pharmacodynamics analysis of the compound fish-goose nasal irrigation agent comprises the following steps: influence of compound fish goose nasal rinse on prevention and treatment effect research on mice with bacterial rhinitis.
1. Material
1.1 Animals
100 BALB/c mice with SPF grade and health qualification, which are male and female halves, have a weight of 18-22 g, and are available from Tian-Bei-Gong Biotechnology Co., changsha, inc., license number: SCXK (Hunan) 2014-0011.
1.2 Medicaments
Compound fish goose nasal rinse is provided by the second affiliated hospital department of medicine, guizhou traditional Chinese medicine university, lot number: 20190712 (the product is brown to tan liquid, the dosage of the product is nasal cavity washing, each nasal cavity is slowly washed for 100mL, 1-2 times a day, the crude drug content is 4g/100mL, the maximum dosage of clinical 60kg body weight is 100mL according to each nostril washing, the crude drug content is 133mg/kg. triamcinolone acetonide nasal spray (specification: 6mL per bottle, 1.1mg of triamcinolone acetonide per 1mL, 120 presses per bottle, 55 mug of triamcinolone acetonide per press), the dosage of the product is nasal cavity internal spray treatment, once a day, two presses per nostril (220 mug/day)), kunming source pharmaceutical Co., ltd, production number 20190825.
1.3 Reagents
Staphylococcus aureus bacterial liquid (concentration is 1.5X10 11/mL, prepared by a morphology laboratory of Guizhou traditional Chinese medicine university), hematoxylin eosin staining kit (Beijing Soy Bao technology Co., ltd., lot number: K195613F), PCT, IL-6, SOD, MDA ELISA kit (Beijing Soy Bao Co., ltd., lot number SEKRT-0402-96T), primary antibodies PCT, IL-6, beta-actin antibody, CELL SIGNA ing Techno1ogy, USA, lot numbers 12835S, 11547S, 4967S respectively; horseradish peroxidase labeled goat anti-rabbit IgG antibody, tsuga gold bridge biotechnology limited, beijing, lot number: ZB-2512; BCA protein concentration assay kit enhancement, shanghai bi yun biotechnology limited, lot number: P0013S.
1.4 Instruments
HSZ-HS3 microscope, chongqing optical instrument factory; VG3S025 Oscillator, ai Ka instruments Inc.; bio-Rad electrophoresis apparatus, guobaale Life medicine Co., ltd; bio-Rad electrophoresis tank, burley life medicine Co., ltd; TGL-20M centrifuge, changshameisen Instrument Equipment Co., ltd; 1510, sameiser instruments, zeeimer instruments limited; 202-IAB electric heating constant temperature drying oven, tianjin Test instruments Co., ltd.
2. Method of
2.1 Modeling
Molding according to a reference method: after the anaesthetized mice were intraperitoneally injected with 1% sodium pentobarbital physiological saline solution, the heads of the mice were sterilized, and the tampons (hemostatic expansion sponge, prepared in a length x width x height=10 mm x 1 mm) were held with forceps, the depth of insertion of the forceps was not more than 1.50mm, and the tampons were inserted into the right nasal cavity of the mice by 4mm (the remainder was temporarily left outside the nostrils). Taking 10 mu L of staphylococcus aureus bacterial liquid from a sample injector, dripping 10 mu L of cotton sliver outside a nasal cavity, then plugging the cotton sliver outside the nostril into the right nostril of a mouse, and continuing for 14d (taking care not to damage nasal mucosa and ensuring that the cotton sliver cannot fall off during the whole experiment, repeating the molding method again if the cotton sliver falls off), taking sneeze, nasal secretion, nasal wiping, nasal inflammation and the like as evaluation indexes according to the scoring standard of the table 1, and taking a score of more than or equal to 6 minutes as successful molding.
TABLE 1 nasal symptom scoring criteria for mice with bacterial rhinitis
2.2 Grouping, administration
After 14d of molding, 60 mice successfully molded are randomly divided into 5 groups, namely a model group, triamcinolone acetonide groups (0.037 mg/kg), high, medium and low dose groups (266, 133 and 66.5 mg/kg) of the compound fish goose nasal cavity flushing agent, and a blank control group is additionally arranged, wherein each group comprises 12 mice and each half of the female and male mice. Nasal irrigation administration, 5 μl/10g, 2 times a day, continuous administration for 14d, nasal drip equivalent of sterile water in the blank and model groups.
2.3 Index detection
2.3.1 Mouse nasal symptom score
After the last administration for 1 hour, sneeze, nasal secretion, nasal abrasion and nasal inflammation were scored according to the scoring table.
2.3.2ELISA detection of mouse serum PCT, IL-6, SOD and MDA content
After nasal symptom scoring is finished, the femoral artery of the anesthetized mice is subjected to non-anticoagulation, centrifugation is carried out for 10min at 3000r/min, and the supernatant is taken. 8 serum samples were randomly taken from each group and assayed for serum PCT, IL-6, SOD, MDA according to ELISA kit instructions.
2.3.3HE staining for observing pathological changes of mouse nasal mucosa
Mice were sacrificed, 6 animals were randomly removed from each group, nasal mucosa tissue was isolated, paraformaldehyde fixed, dehydrated with alcohol gradient, transparent, waxed, embedded, sectioned, stained, dehydrated, transparent, and capped, and the pathological condition of nasal mucosa was observed under a microscope.
2.3.3Westernblot detection of PCT and IL-6 protein expression in mouse nasal mucosa
Nasal mucosa of 6 mice were taken and rapidly frozen in liquid nitrogen and stored in a-80 ℃ refrigerator. Taking out during detection, mashing in a mortar, adding lysate, homogenizing at low temperature with an ultrasonic cell disrupter, centrifuging for 10min at 12000r/min, and measuring protein amount by BCA method. Taking 30 mug protein sample to carry out SDS-polyacrylamide gel electrophoresis, rotating a mould, sealing 5% skim milk on the membrane for 2 hours at room temperature, respectively adding primary antibodies against PCT, IL-6 and beta-actin, incubating overnight at 4 ℃, adding secondary antibodies marked by horseradish peroxidase, incubating, developing, shooting and analyzing by a gel imaging analysis system, and adopting QuantiyOne analysis software to analyze the grey value of the band.
2.4 Statistical treatment
The SPSS21.0 statistical software is adopted, experimental data are expressed by mean value +/-standard deviation (x +/-S), the comparison between groups adopts single-factor analysis of variance, the comparison between groups adopts LSD-t test, and p <0.05 is the difference with significance.
3 Results
3.1 Effect of Compound fish goose nasal rinse on model mouse nasal symptom scoring
As can be seen from table 2, the nasal symptoms of mice in the model group were evident, and nasal secretion and nasal inflammation scores were all significantly increased (p < 0.01) when compared with the blank group. Compared with the model group, the nasal symptom scores of the triamcinolone acetonide group and the high-dose group mice are obviously reduced (p <0.05, p < 0.01); the mid-dose group had no significant nasal rub scores, and the remaining symptom scores were all significantly reduced (p <0.05, p < 0.01); the low dose group showed a significant decrease in sneezing symptom score alone (p < 0.05).
TABLE 2 influence of Compound fish-goose nasal rinse on model mouse nasal symptom scoren＝12)/>
Note that: #p<0.05,## p <0.01 compared to the placebo group; *p<0.05,** p <0.01 compared to model set. 3.2 Effect of Compound fish-goose nasal rinse on serum PCT, IL-6, SOD and MDA content of model mice
As can be seen from Table 3, the serum PCT, IL-6 and MDA contents of mice in the model group are all significantly increased and the SOD level is significantly decreased (p < 0.01) compared with the blank control group. Compared with the model group, the serum PCT and MDA of each administration group are obviously reduced, the serum IL-6 content of each administration group except triamcinolone acetonide group is obviously reduced, and the SOD content is obviously increased (p <0.05, p < 0.01).
TABLE 3 influence of Compound fish-goose nasal rinse on serum PCT, IL-6, SOD and MDA content of model micen＝8)
Note that: #p<0.05,## p <0.01 compared to the placebo group; *p<0.05,** p <0.01 compared to model set. 3.3 influence of the compound fish goose nasal cavity irrigation agent on pathological changes of nasal mucosa of model mice the nasal mucosa cilia and epithelial cells of mice of a blank control group are orderly arranged, the thickness of the epithelial layer is normal, and mucous membrane and submucosa are rarely infiltrated with neutrophils, so that congestion and tissue edema are avoided. Compared with the blank control group, the nasal mucosa of the mice in the model group can be seen to have obvious tissue edema, vasodilation, red blood cell exudation, massive neutrophil infiltration and thinned epithelium. Compared with the model group, the nasal mucosa tissue edema of the triamcinolone acetonide group mice is slightly reduced, the epithelial layer is slightly thickened, the epithelial cells are slightly orderly arranged, a small amount of neutrophil infiltration is realized, and the blood vessel is slightly expanded; the nasal cavity flushing agent for compound fish geese reduces nasal mucosa tissue edema of mice in high, medium and low dose groups, reduces red blood cell exudation, thickens epithelial layer, and has uneven cell arrangement and partial neutrophil infiltration.
3.4 Effect of Compound fish goose nasal rinse on PCT, IL-6 protein expression in nasal mucosal tissue of model mice
As can be seen from Table 4, PCT, IL-6 protein expression was significantly increased in the nasal mucosal tissue of mice in the model group (p < 0.01) compared to the blank group. Compared with the model group, each administration group can obviously reduce the expression level of PCT protein in the nasal mucosa tissue of the mice; the other administration groups except the low dose group can obviously reduce the expression level of IL-6 protein (p <0.05, p < 0.01).
TABLE 4 influence of Compound fish-goose nasal rinse on PCT-6 protein expression in nasal mucosal tissue of model micen＝6)/>
Note that: #p<0.05,## p <0.01 compared to the placebo group; *p<0.05,** p <0.01 compared to model set.
Influence of the compound fish goose nasal irrigation agent on HO-1, keap1, nrf2 and SOD-1 protein expression in nasal mucosa tissue of model mice.
Procalcitonin (PCT) is a calcitonin propeptide secreted by thyroid C cells in concentrations related to both pathogenic bacterial infection and the extent of infection, and is one of the pro-inflammatory biomarkers of bacterial infection, released as a response to bacterial toxins and bacterial-specific pro-inflammatory mediators. In patients with bacterial infection rhinitis, PCT levels in the blood of the patient are significantly increased. PCT is produced by bacterial endotoxins, TNF- α, IL-6 and other factors acting on neuroendocrine cells or special cells of the liver, spleen, kidney, lung, and PCT may be a secondary inflammatory factor that is not directly involved in initiating sepsis response itself, but may amplify and exacerbate sepsis pathological processes. In the study, the levels of PCT, IL-6 and TNF-alpha in serum of a model rat are obviously increased, the levels of PCT and IL-6 proteins in nasal mucosa tissues of the rat are obviously increased, and the pathological damage of the nasal mucosa tissues of the rat is obvious, and symptoms such as obvious runny nose, sneeze, nasal inflammation and nose wiping appear, which indicate that the PCT participates in inflammatory reaction and pathological damage, and after the treatment of the compound fish-goose nose drops, the compound fish-goose nose drops can obviously inhibit the expression of the PCT and IL-6 proteins in the nasal mucosa tissues of the rat, reduce the content of PCT, IL-6 and TNF-alpha in the serum of the rat and inhibit the infiltration of inflammatory cells, which indicates that the compound fish-goose nose drops can inhibit the inflammatory reaction by regulating the PCT and improve the symptoms of mice with bacterial rhinitis.
Inflammatory cells in nasal mucosa tissues of rhinitis patients infiltrate to generate a large amount of inflammatory cytokines TNF-alpha, IL-6, IL-8 and the like and oxygen free radicals, and the oxygen free radicals participate in and generate decomposition products MDA and the like through lipid peroxidation reaction, so that cell membrane results are damaged, and inflammatory factors are further promoted to be released. SOD scavenges oxygen radicals and inhibits lipid peroxidation and inflammatory reactions in nasal mucosal tissue. In the study, MDA level in serum of a model rat is obviously increased, SOD level is obviously reduced, which indicates lipid peroxidation damage, and after treatment by the fish-goose nasal cavity flushing agent, the fish-goose nasal cavity flushing agent can obviously increase SOD level and reduce MDA content, which indicates that the compound fish-goose nasal cavity flushing agent can inhibit lipid peroxidation and inflammatory reaction in nasal mucosa tissues by regulating SOD to remove free radicals.
The compound fish goose nasal wash can reduce the content of PCT, IL-6, TNF-alpha and MDA in serum of a mouse model of bacterial rhinitis, raise SOD level in serum, inhibit protein expression of PCT and IL-6 in nasal mucosa tissues, and reduce infiltration and lipid peroxidation of inflammatory cells in the nasal mucosa tissues, thereby improving symptoms of allergic rhinitis. These show that the compound fish goose nasal rinse has good protection effect on staphylococcus aureus induced bacterial rhinitis of mice.
Based on the formula and the preparation method of the compound fish-goose nasal rinse provided above, the following four specific examples and implementation schemes thereof are as follows:
example 1: preparation of Standard formulation
According to the formula in claim 1, 20g of centipeda minima, 15g of baical skullcap root, 12g of ephedra herb, 12g of cocklebur fruit, 20g of dahurian angelica root, 12g of heartleaf houttuynia herb, 10g of magnolia flower and 0.2g of borneol are taken.
The preparation is carried out according to the preparation method in claim 2 without any change.
Example 2: flos Magnoliae enhanced extraction
The formulation of claim 1, but the amount of magnolia is increased to 15g.
The method for extracting flos Magnoliae of claim 3, wherein the extraction temperature is 140 ℃ and the extraction time is 6 hours to increase the content of effective components in flos Magnoliae extract.
Example 3: optimizing sterilization process
The preparation is carried out according to the formulation of claim 1.
In the steam-through sterilization in claims 6 and 7, the temperature of the high-temperature short-time treatment is adjusted to 105℃and the internal pressure is adjusted to 0.14MPa to ensure a better sterilization effect.
Example 4: concentration optimization
The preparation is carried out according to the formulation of claim 1.
In claim 5, the filtrate is concentrated to a density of 1.35g/mL, and the extract is further concentrated to make it more suitable for the subsequent step.
Each of the embodiments is tailored or optimized for a particular step or ingredient to meet different needs or to improve the performance of the product.
The foregoing is merely illustrative of specific embodiments of the present invention, and the scope of the invention is not limited thereto, but any modifications, equivalents, improvements and alternatives falling within the spirit and principles of the present invention will be apparent to those skilled in the art within the scope of the present invention.
Claims (9)
1. The compound fish-goose nasal irrigation solution is characterized by comprising 20g of centipeda minima, 15g of radix scutellariae, 12g of ephedra, 12g of fructus xanthil, 20g of radix angelicae, 12g of herba houttuyniae, 10g of flos magnoliae and 0.2g of borneol according to the weight gram.
2. A method for preparing the compound fish-goose nasal rinse according to claim 1, comprising the following steps:
Sequentially weighing centipeda minima, baical skullcap root, ephedra herb, cocklebur fruit, dahurian angelica root, heartleaf houttuynia herb, magnolia flower and borneol according to a formula;
step two, decocting magnolia flower with 4 times of water for 10 minutes, and collecting water decoction to obtain magnolia flower water extract, and keeping dregs for later use;
step three, decocting the residues of centipeda minima, baical skullcap root, ephedra herb, cocklebur fruit, dahurian angelica root, heartleaf houttuynia herb and magnolia flower with 8 times of water, keeping micro-boiling for 1h, and separating out decoction when the decoction is hot; decocting the residue with 8 times of water twice, collecting decoction, filtering, concentrating the filtrate to obtain water decoction concentrate;
Step four, combining the magnolia flower water extract prepared in the step two with the water decoction concentrated solution prepared in the step three, centrifuging, and separating the supernatant to obtain a compound fish-goose nasal cavity flushing agent liquid medicine;
Step five, adding 1g of ethylparaben and 0.2g of borneol into a proper amount of 95% medicinal ethanol for dissolution, adding 6001g of polyethylene glycol, stirring for dissolution, and adding into the compound fish-goose nasal rinse liquid medicine after uniform mixing; adding purified water to 1000mL, stirring, placing in a sterilizing container, and sterilizing with circulating steam to obtain the compound fish goose nasal rinse.
3. The method for preparing the compound fish-goose nasal rinse according to claim 2, wherein the method for preparing the magnolia flower water extract in the first step comprises the following steps:
(1) Placing flos Magnoliae in a drying device for drying, and placing in a pulverizer for pulverizing to obtain Xin Yifen; mixing flos Magnoliae powder with 10-20 times of water, and placing into a pressure reactor, and performing primary extraction under subcritical conditions to obtain primary extract and primary solid residue;
(2) Adding 8-15 times of water into the first-stage solid residue obtained in the step (1) and placing the mixture into a pressure reactor for secondary extraction to obtain a secondary extract and a second-stage solid residue; combining the primary extract and the secondary extract obtained in the step (1) to obtain a total magnolia extract;
(3) Concentrating the flos magnoliae total extract obtained in the step (2) under reduced pressure at 50-55 ℃ to obtain flos magnoliae concentrated solution; adding ethanol with the volume of 4-6 times into the magnolia flower concentrated solution for precipitation, and centrifuging to obtain crude polysaccharide; deproteinizing the crude polysaccharide by a Sevage method, decolorizing, and dialyzing to obtain flos Magnoliae water extract.
4. The method for preparing the compound fish-goose nasal rinse agent as claimed in claim 3, wherein the extraction temperature in the step (1) is 110-150 ℃ and the extraction time is 4-8 h;
The precipitation temperature in the step (3) is 0-4 ℃, and the precipitation time is 24-48 h; decolorizing with D101 macroporous resin, and dialyzing with 3500Da dialysis bag for 24-48 hr.
5. The method for preparing the compound fish-goose nasal rinse agent according to claim 2, wherein in the second step, water with the weight 3-6 times of the weight of the medicine material is added for the first time, and the filtrate is concentrated to the density of 1.33g/mL;
the centrifugation conditions in step three are: centrifuging for 5-15 min at 4000-5500 r/min;
and step four, the circulating steam sterilization time is 40-60 min.
6. The method for preparing the compound fish-goose nasal rinse agent as claimed in claim 2, wherein the step four of placing the compound fish-goose nasal rinse agent liquid medicine in a sterilization container for circulating steam sterilization comprises:
(1) Placing the compound fish-goose nasal cavity flushing agent liquid medicine with fixed volume into a sterilizing container in a circulating water vapor sterilizing cabinet;
(2) Introducing water vapor into the circulating water vapor sterilization cabinet for high-temperature short-time treatment;
(3) And taking out when the pressure in the circulating steam sterilization cabinet is reduced to zero, cooling in a clean room, and packaging to obtain the compound fish-goose nasal rinse.
7. The method for preparing the compound fish-goose nasal rinse agent as claimed in claim 6, wherein the temperature for starting the high-temperature short-time treatment in the step (2) is 90-110 ℃, and the internal pressure is 0.12-0.15 Mpa.
8. The method of using the compound fish-goose nasal rinse of claim 8, further comprising:
performing nasal cavity flushing by using 200mL of the compound fish-goose nasal cavity flushing agent;
is suitable for adults 1-2 times per day.
9. An anti-inflammatory detumescent nasal cavity cleaning medicament, which is characterized in that the anti-inflammatory detumescent nasal cavity cleaning medicament comprises the compound fish-goose nasal rinse according to claim 1.
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