Compound betamethasone nasal washing agent and preparation method thereof

Abstract

The invention discloses a compound betamethasone nasal washing agent and a preparation method thereof. The compound betamethasone nasal washing agent comprises betamethasone dipropionate, betamethasone sodium phosphate, ethanol, sodium chloride, sodium carboxymethyl cellulose, methylparaben sodium, Tween 80 and water for injection. The compound betamethasone nasal washing agent treats allergic rhinitis in a nasal delivery mode, is free of irritation, low in medicine absorption, quick in effect taking and capable of playing a local role to the maximum extent, and side effects are reduced. The compound betamethasone nasal washing agent is continuously, safely and effectively used for treating AR, and has clinical significance for improving nasal cavity ventilation and controlling nasal symptoms so as to improve the life quality level of AR patients. Compared with common nasal glucocorticoid preparations budesonide and azelastine, the nasal glucocorticoid preparation is more remarkable in curative effect.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines for treating rhinitis, and particularly relates to a compound betamethasone nasal wash and a preparation method thereof. Background Art

[0002] Allergic rhinitis (AR), also known as allergic rhinitis, is a serious global health problem. 10-30% of adults and about 40% of minors suffer from this disease. Epidemiological surveys and studies show that the incidence of allergic rhinitis continues to increase. The World Health Organization estimates that the number of new allergic rhinitis patients exceeds 400 million each year. At present, the treatment of this disease mainly focuses on nasal glucocorticoids, histamine and leukotriene receptor blockers, which focus on relieving symptoms and are the first-line clinical drugs.

[0003] Betamethasone is a member of the glucocorticoid family. Because of its powerful anti-inflammatory, anti-allergic and immunosuppressive effects, it is widely used in the clinic to treat asthma, angioedema, Crohn's disease and other diseases. Studies have shown that compound betamethasone has a good therapeutic effect on rhinitis (including allergic rhinitis). At present, compound betamethasone is mainly administered by intramuscular injection or intra-articular injection to achieve systemic or local administration. In the studies on compound betamethasone preparations in rhinitis, most of them use intramuscular injection or inferior turbinate injection and bilateral nasal injection. These injection methods may cause various adverse reactions caused by corticosteroids, such as abnormalities of the musculoskeletal, gastrointestinal, skin, nervous system, endocrine system and water and electrolyte disorders, etc., and the injection method of the inferior turbinate and bilateral nasal wing is more difficult, and professional training of operators is required, resulting in poor patient compliance.

[0004] Nasal administration is absorbed through the nasal mucosa to exert local or systemic therapeutic effects. The nasal mucosa has a large surface area, a loose and hydrophilic structure, and contains a large number of capillaries. The drug takes effect quickly and is easy to use, and patient compliance is good.

[0005] In view of this, there is an urgent need to develop a compound betamethasone nasal wash that can treat allergic rhinitis through nasal administration, and achieve a non-irritating administration process, less drug absorption, and rapid onset of action, which can maximize the local effect and reduce the side effects of the treatment. Summary of the invention

[0006] The present invention aims to at least partially overcome the above technical problems and / or other potential problems existing in the prior art: to provide a compound betamethasone nasal wash and a preparation method thereof. The compound betamethasone nasal wash of the present invention is used to treat allergic rhinitis by nasal administration, has no irritation, less drug absorption, fast onset, can maximize local effects, and reduce side effects.

[0007] The technical solution of the present invention is as follows: a compound betamethasone nasal wash, comprising betamethasone dipropionate, betamethasone sodium phosphate, ethanol, sodium chloride, sodium carboxymethyl cellulose, sodium hydroxybenzoate, Tween 80 and water for injection.

[0008] Preferably, the content of each component is: betamethasone dipropionate 0.005-0.05 mg / mL, betamethasone sodium phosphate 0.001-0.02 mg / mL, ethanol content by volume ratio is 0.1%-0.3%, sodium chloride 5-10 mg / mL, sodium carboxymethyl cellulose 5-10 mg / mL, sodium hydroxybenzoate 0.1-0.5 mg / mL, Tween 80 content by volume ratio is 0.1-0.3%; the balance is water for injection.

[0009] Preferably, the mass ratio of betamethasone dipropionate calculated as betamethasone to betamethasone sodium phosphate calculated as betamethasone is 2.5:1.

[0010] Specifically, the content of each component is as follows: betamethasone dipropionate 0.0129 mg / mL, betamethasone sodium phosphate 0.0053 mg / mL, ethanol content by volume ratio 0.2%, sodium chloride 7.5 mg / mL, sodium carboxymethyl cellulose 7.5 mg / mL, sodium hydroxybenzoate 0.3 mg / mL, Tween 80 content by volume ratio 0.2%; the remainder is water for injection.

[0011] Specifically, the content of each component is as follows: betamethasone dipropionate 0.0258 mg / mL, betamethasone sodium phosphate 0.0106 mg / mL, ethanol content by volume ratio 0.2%, sodium chloride 7.5 mg / mL, sodium carboxymethyl cellulose 7.5 mg / mL, sodium hydroxybenzoate 0.3 mg / mL, Tween 80 content by volume ratio 0.2%; the remainder is water for injection.

[0012] The present invention also provides a method for preparing the compound betamethasone nasal wash, comprising the following steps:

[0013] S1: dissolve betamethasone sodium phosphate, sodium chloride, Tween 80 and sodium methylparaben in water for injection, and filter to obtain a filtrate;

[0014] S2: adding sodium carboxymethyl cellulose to water for injection and heating it to dissolve it, and then mixing it with the filtrate obtained in step S1 to obtain a mixed solution;

[0015] S3: dissolving betamethasone dipropionate in ethanol, gradually adding the mixed solution obtained in step S2, and grinding evenly by liquid addition grinding method to obtain the compound betamethasone nasal wash.

[0016] The beneficial effects of the present invention are as follows: the compound betamethasone nasal wash of the present invention can effectively reduce the systemic toxicity of the compound betamethasone, treat allergic rhinitis by nasal administration, have no irritation, less drug absorption, fast onset, can maximize local effects, and reduce side effects. From a physical and chemical perspective, the betamethasone sodium phosphate component is dissolved in physiological saline and can be quickly absorbed by the nasal mucosa, thereby timely controlling the rapid phase reaction of AR. At the same time, another effective ingredient, betamethasone dipropionate, is slightly soluble in the solvent and can remain on the surface of the nasal mucosa after nasal washing of AR patients, and continuously releases the effective ingredients in a slow manner to relieve nasal symptoms, has a long-term therapeutic effect, and controls the delayed phase reaction of AR. From the perspective of synergistic effect, when betamethasone sodium phosphate and betamethasone dipropionate are used in combination, they can mutually enhance the effect on the nasal mucosa, accelerate the reduction of inflammatory response, reduce allergic symptoms, and thus significantly improve the symptoms of patients with rhinitis. Combined with the strengthening of the adsorption of the above components on the surface of the nasal mucosa by carboxymethyl cellulose, this synergistic mechanism makes the treatment more comprehensive and effective, and improves the success rate of treatment and the quality of life of patients. The use of the compound betamethasone nasal wash of the present invention to treat AR is also a safe, convenient and inexpensive method, which has the effect of diluting mucus, improving mucociliary clearance function, reducing mucosal edema and reducing the allergen load in the nasal cavity and sinuses during the rinsing process. Commonly used flushing solutions in the clinic include normal saline, deep sea saline and hypertonic saline. Nasal irrigation can significantly reduce the severity of symptoms without adverse reactions. The osmotic pressure and pH value of normal saline are close to those of human body fluids, contain trace elements and minerals, help to restore the function of ciliary mucus, and improve the physiological state of the nasal cavity. In the present invention, the composition of the compound betamethasone nasal wash can imitate sea salt water, which has a similar pH value and sodium chloride component, and contains a second-generation glucocorticoid component, which has a synergistic effect on the local anti-inflammatory effect of the nasal mucosa.

[0017] In summary, the compound betamethasone nasal wash of the present invention is continuously safe and effective in treating AR, and has clinical significance for improving nasal ventilation, controlling nasal symptoms, and thus improving the quality of life of AR patients. Compared with the common nasal glucocorticoid preparations budesonide and azelastine, the therapeutic effect is more significant. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The following are the pathological morphological changes of nasal mucosa of guinea pigs in each group in the example (HE staining, ×100); wherein: A: budesonide group; B: azelastine hydrochloride group; C: mometasone furoate group; D: betamethasone low-dose group; E: betamethasone medium-dose group; F: betamethasone high-dose group; G: model group; H: normal group.

[0019] Figure 2The following are the pathological morphological changes of lung tissues of guinea pigs in each group in the example (HE staining, ×200); wherein: A: budesonide group; B: azelastine hydrochloride group; C: mometasone furoate group; D: betamethasone low-dose group; E: betamethasone medium-dose group; F: betamethasone high-dose group; G: model group; H: normal group. DETAILED DESCRIPTION

[0020] The technical scheme of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work are within the scope of protection of the present invention. It should be pointed out that the following detailed descriptions are exemplary and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by ordinary technicians in the technical field to which the present application belongs.

[0021] Example 1

[0022] The composition of the compound betamethasone nasal wash of the present embodiment is: betamethasone dipropionate is 10mg (betamethasone dipropionate is 12.9mg) and betamethasone sodium phosphate is 4mg (betamethasone sodium phosphate is 5.3mg) according to betamethasone, ethanol 2ml, sodium chloride 7.5g, sodium carboxymethyl cellulose 7.5g, sodium methylparaben 0.3g, Tween 80 2ml, and water for injection is added to 1000mL.

[0023] The preparation method of the compound betamethasone nasal wash of the present embodiment is as follows:

[0024] S1: Dissolve 5.3 mg of betamethasone sodium phosphate, 7.5 g of sodium chloride, 2 mL of Tween 80, and 7.5 g of sodium methylparaben in 400 mL of water for injection, and filter to obtain a filtrate;

[0025] S2: Take 7.5 g of sodium carboxymethyl cellulose and add 500 mL of water for injection, heat to dissolve it, and mix it with the filtrate obtained in step S1 to obtain a mixed solution;

[0026] S3: Dissolve 12.9 mg of betamethasone dipropionate in 2 mL of ethanol, gradually add 2 mL of the mixed solution obtained in step S2, grind evenly by liquid addition grinding method, mix with the remaining mixed solution obtained in step S2, and finally add water for injection to 1000 mL to obtain the compound betamethasone nasal wash.

[0027] Example 2

[0028] The composition of the compound betamethasone nasal wash of the present embodiment is: betamethasone dipropionate is 20 mg (betamethasone dipropionate is 25.8 mg) and betamethasone sodium phosphate is 8 mg (betamethasone sodium phosphate is 10.6 mg) according to betamethasone, ethanol 2 ml, sodium chloride 7.5 g, sodium carboxymethyl cellulose 7.5 g, sodium methylparaben 0.3 g, Tween 80 2 ml, and water for injection is added to 1000 mL.

[0029] The preparation method of the compound betamethasone nasal wash of the present embodiment is as follows:

[0030] S1: Take 10.6 mg of betamethasone sodium phosphate, 7.5 g of sodium chloride, 2 mL of Tween 80, and 0.3 g of sodium methylparaben (sodium methylparaben) and dissolve them in 400 mL of water for injection, and filter to obtain a filtrate;

[0031] S2: Take 7.5 g of sodium carboxymethyl cellulose and add 500 mL of water for injection, heat to dissolve it, and mix it with the filtrate obtained in step S1 to obtain a mixed solution;

[0032] S3: Dissolve 25.8 mg of betamethasone dipropionate in 2 mL of ethanol, gradually add 2 mL of the mixed solution obtained in step S2, grind evenly by liquid addition grinding method, mix with the remaining mixed solution obtained in step S2, and finally add water for injection to 1000 mL to obtain the compound betamethasone nasal wash.

[0033] Example 2 Pharmacological Experiment

[0034] 1.1 Materials

[0035] 1.1.1 Animals and groups

[0036] A total of 64 guinea pigs, male and female, aged 2 to 3 months were randomly divided into 8 groups, namely, budesonide spray group, azelastine hydrochloride nasal spray group, mometasone furoate nasal spray group, low-dose compound betamethasone group, medium-dose compound betamethasone group, high-dose compound betamethasone group, model group and normal control group, with 8 pigs in each group.

[0037] 1.1.2 Drugs and reagents

[0038] Budesonide spray: 120 sprays / tube, 64ug / spray, 1.28mg / ml, batch number BT218, provided by McNeil AB, for human use twice a day, morning and evening, a total of 256ug. When used in guinea pigs, dilute each milliliter of the solution with saline to 30ml, and take 100ul of the diluted solution for nasal drops.

[0039] Azelastine hydrochloride nasal spray: 10ml / tube, 0.14mg / spray, 1mg / ml, batch number F2203953, provided by Madaus GmbH, for human use twice a day, morning and evening, a total of 560ug. For guinea pigs, dilute each milliliter of the solution with saline to 10ml, and take 100ul of the diluted solution for nasal drops.

[0040] Mometasone furoate nasal spray: 60 presses / tube, 50ug / press, batch number X015122, provided by Schering-Plough Labo N.V., once a day for humans, 200ug in total. When used on guinea pigs, dilute each milliliter of the solution with saline to 30ml, and take 100ul of the diluted solution and drip into the nose.

[0041] Guinea pig immunoglobulin E (IgE) ELISA kit: Product No. MB-2480B; guinea pig interleukin 6 (IL-6) ELISA kit: Product No. MB-2491B; guinea pig histamine (HIS) ELISA kit: Product No. MB-2475B, all produced by Jiangsu ELISA Biotechnology Co., Ltd., batch number: 202404.

[0042] Aluminum hydroxide [Al(OH)3]: 500 g / bottle, molecular weight 78.0, provided by Shanghai McLean Biochemical Technology Co., Ltd.

[0043] Ovalbumin (OVA): 5 g / bottle, batch number: C14078774, provided by Shanghai McLean Biochemical Technology Co., Ltd.

[0044] OVA suspension: 1 ml of sodium chloride solution, 0.3 mg of OVA (powder), 30 mg of Al(OH)3 (powder).

[0045] OVA solution: 1 ml of sodium chloride solution, 20 mg of OVA (powder) (concentration 2%).

[0046] Example 2 Nasal wash: comprising betamethasone dipropionate 0.0258 mg / mL, betamethasone sodium phosphate 0.0106 mg / mL, ethanol 0.2% (volume ratio), sodium chloride 7.5 mg / mL, sodium carboxymethyl cellulose 7.5 mg / mL, sodium hydroxybenzoate 0.3 mg / mL, Tween 80 0.2% (volume ratio) and the balance water. When used in high doses for guinea pigs, dilute each milliliter of the drug solution with normal saline to 17.5 ml, and take 100 ul of the diluted drug solution for nasal drops; the medium dose for guinea pigs is diluted by one time for the high dose; the low dose for guinea pigs is diluted by one time for the medium dose.

[0047] 1.2 Model preparation

[0048] 1.2.1 Systemic basal sensitization: Except for 8 guinea pigs in the normal control group, the remaining guinea pigs were intraperitoneally injected with the above OVA suspension at a dose of 1.0 mL / guinea pig, once every other day for 7 consecutive times (a total of 14 days);

[0049] 1.2.2 Nasal provocation: From the 15th day, except for the normal control group, the other 7 groups of guinea pigs were challenged with the above-mentioned 2% OVA solution by nasal drops (bilaterally), 100 μL per guinea pig, for 3 consecutive days to create an AR model; within 30 minutes after the last administration, the guinea pigs were observed for scratching their noses, sneezing, and clearing their nasal mucus, and the symptom score table (see Table 1) was used as the reference, and a total score of >5 points was considered a successful model.

[0050] 1.2.3 The normal control group was intraperitoneally injected with 1.0 mL of normal saline plus 30 mg of aluminum hydroxide, and then nasally dripped with normal saline (bilaterally) as a control, with the same time and dosage as the other groups.

[0051] After the model was successfully established, the corresponding drugs were administered to the guinea pigs in each group of the model using a micropipette, 0.05 ml / time on each side, once / day, for 7 consecutive times. The model group and the normal control group were given an equal volume of saline drops in the same way. The behavioral changes of the guinea pigs were observed within 30 minutes after the last administration. The guinea pigs were anesthetized with 10% chloral hydrate, and blood was collected from the abdominal aorta to test the blood routine (white blood cell, lymphocyte, red blood cell and platelet count). At the same time, the serum was separated, and the IgE, HIS and IL-6 levels in the serum were detected by double antibody one-step sandwich enzyme-linked immunosorbent assay (ELISA). After the blood was collected from the abdominal aorta, the cervical vertebra was quickly removed and the animals were killed. The rib cartilages on both sides were cut upward to the sternoclavicular joint to expose the chest cavity and remove the largest lobe of the lungs. The nasal passages were cut open and the nasal mucosal tissues on both sides of the nasal septum were taken. The cells were fixed with 10% formaldehyde and subjected to routine treatments such as dehydration, embedding, sectioning, and HE staining. The pathological morphological changes were observed under a microscope.

[0052] Table 1 AR guinea pig behavioral scoring criteria

[0053] symptom 1 point 2 points 3 points Itchy nose Wipe your nose several times Scratching nose and face constantly Rub everywhere sneeze 1 to 3 4 to 10 11 or more Clear tears Flow to the front of the nose Beyond the anterior nasal aperture Tears streaming down one's face

[0054] 1.3 Experimental results:

[0055] 1.3.1 Effect on the overall condition of guinea pigs with allergic rhinitis

[0056] Except for the normal group of guinea pigs, the other groups began to show varying degrees of nasal allergy symptoms and poor fur gloss in the second week after intraperitoneal injection of OVA suspension, and the above symptoms gradually worsened with the increase in the number of administrations and the local stimulation of OVA solution nasal drops. The nasal symptoms of guinea pigs administered with betamethasone were alleviated, and the fur gloss was not significantly changed before and after the experiment in the normal group and the model group.

[0057] 1.3.2 Effects on body weight and lung index of AR guinea pigs. The results are shown in Table 2

[0058] Table 2 Effects of AR on body weight and lung index of guinea pigs ( n=8)

[0059]

[0060] As shown in Table 2, the weight gain of AR model guinea pigs induced by OVA decreased significantly, which was significantly different from that of the normal group guinea pigs (P<0.001). The weight of AR model guinea pigs increased to a certain extent after administration of betamethasone, and the weight of high-dose betamethasone group was significantly different from that of the model group (P<0.05). The lung index of AR model guinea pigs induced by OVA increased to a certain extent, which was significantly different from that of the normal group guinea pigs (P<0.05). The lung index of AR model guinea pigs induced by OVA increased to a certain extent, which was significantly different from that of the normal group guinea pigs (P<0.05). The administration of betamethasone had no significant effect on the lung index of AR model guinea pigs.

[0061] 1.3.3 Effects on AR guinea pig behavior. Results are shown in Table 3

[0062] Table 3 Effects on behavioral symptom scores of AR guinea pigs ( n=8)

[0063]

[0064]

[0065] As shown in Table 3, the guinea pigs in the normal group occasionally scratched their noses, but did not have clear runny noses. The guinea pigs in the model group had prominent AR symptoms such as scratching their noses, clear runny noses, and frequent sneezing. The guinea pigs given medium and high doses of betamethasone had significantly alleviated the above typical AR symptoms. Compared with the model group, the scores and the difference in scores after treatment were significantly different (P<0.01-0.001). The results showed that betamethasone had the effect of relieving AR symptoms.

[0066] 1.3.4 Effect on blood routine of AR guinea pigs. The results are shown in Table 4

[0067] Table 4 Effects of AR on blood routine in guinea pigs ( n=8)

[0068]

[0069] As shown in Table 4, the WBC of AR model guinea pigs increased to a certain extent compared with the normal group, and there was a significant difference compared with the normal group (P<0.05); the RBC of AR guinea pigs decreased to a certain extent compared with the normal group, and there was a significant difference compared with the normal group (P<0.01); after administration of betamethasone, there was no obvious effect on the WBC, LY, RBC and PLT of AR guinea pigs (P﹥0.01).

[0070] 1.3.5 Effects on the levels of IgE, HIS and IL-6 in the serum of AR guinea pigs. The results are shown in Table 5

[0071] Table 5 Effects of AR on serum IgE, HIS and IL-6 levels in guinea pigs ( n=8)

[0072]

[0073]

[0074] As can be seen from Table 5, the levels of IgE, IL-6 and HIS in the serum of AR guinea pigs were significantly higher than those in the normal group (P<0.001). Betamethasone reduced the levels of IgE, IL-6 and HIS in the serum of AR guinea pigs, among which the levels of serum IgE and HIS were significantly different from those in the model group (P<0.05~0.001).

[0075] 1.3.6 Effects on pathological morphology of AR guinea pigs. Results are shown in Figure 1-2 shown.

[0076] Depend on Figure 1 It can be seen that the epithelial cell structure of the nasal mucosa of guinea pigs in the normal group was intact, the glands and blood vessels had no obvious changes, and inflammatory cell infiltration was occasionally seen. Compared with the normal group, the guinea pigs in the AR model group had more exudates outside the nasal mucosa, an increase in the number of goblet cells, hyperplasia of the glands in the lamina propria, and aggregation and infiltration of inflammatory cells; betamethasone and positive drugs in each dose group had a great improvement on the nasal mucosa of guinea pigs compared with the model group, with less exudates outside the nasal mucosa, less inflammatory cell infiltration, and mild hyperplasia of the glands.

[0077] Depend on Figure 2 It can be seen that the lung tissue structure and morphology of guinea pigs in the normal group were normal; compared with the normal group, the guinea pigs in the AR model group had obvious alveolar inflammatory cell infiltration, alveolar cavity congestion and edema, more alveolar fusion, and interstitial thickening. High-dose betamethasone and positive drugs significantly improved the morphology of guinea pig lung tissue.

[0078] 1.4 Conclusion:

[0079] 1.4.1 Compound betamethasone nasal wash has a certain effect on improving AR symptoms such as nose scratching, runny nose, and sneezing in AR guinea pigs.

[0080] 1.4.2 Compound betamethasone nasal wash significantly reduced the levels of IgE and HIS in the serum of AR model guinea pigs, but had no significant effect on the routine blood indicators of WBC, LY, RBC and PLT of AR model guinea pigs.

[0081] 1.4.3 Compound betamethasone nasal wash improved the nasal mucosa and lung tissue structure of AR guinea pigs, indicating that the nasal wash has a certain protective and repairing effect on the nasal mucosa and lung tissue of AR guinea pigs.

[0082] 1.5 Summary

[0083] The compound betamethasone nasal wash of the present invention is continuously safe and effective in treating allergic rhinitis. Compared with common nasal glucocorticoid preparations budesonide and azelastine, the compound betamethasone nasal wash has a more significant therapeutic effect on improving nasal ventilation.

[0084] The above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit them. Any other changes, modifications, substitutions, combinations and simplifications made without departing from the spirit and principles of the present invention shall be considered as equivalent replacement methods and shall be included in the protection scope of the present invention.

Claims

1. A compound betamethasone nasal wash, It is characterized in that Contains betamethasone dipropionate, betamethasone sodium phosphate, ethanol, sodium chloride, sodium carboxymethyl cellulose, sodium hydroxybenzoate, Tween 80 and water for injection.

2. The compound betamethasone nasal wash according to claim 1, It is characterized in that The content of each component is: betamethasone dipropionate 0.005~0.05 mg / mL, betamethasone sodium phosphate 0.001~0.02 mg / mL, ethanol content by volume ratio 0.1%~0.3%, sodium chloride 5~10 mg / mL, sodium carboxymethyl cellulose 5~10 mg / mL, sodium hydroxybenzoate 0.1~0.5 mg / mL, Tween 80 content by volume ratio 0.1~0.3%; the balance is water for injection.

3. The compound betamethasone nasal wash according to claim 2, It is characterized in that The mass ratio of the betamethasone dipropionate calculated as betamethasone to the betamethasone sodium phosphate calculated as betamethasone is 2.5:

1.

4. The compound betamethasone nasal wash according to claim 3, It is characterized in that The specific content of each component is: betamethasone dipropionate 0.0129 mg / mL, betamethasone sodium phosphate 0.0053 mg / mL, ethanol content by volume ratio 0.2%, sodium chloride 7.5 mg / mL, sodium carboxymethyl cellulose 7.5 mg / mL, sodium hydroxybenzoate 0.3 mg / mL, Tween 80 content by volume ratio 0.2%; the remainder is water for injection.

5. The compound betamethasone nasal wash according to claim 4, It is characterized in that The specific content of each component is: betamethasone dipropionate 0.0258 mg / mL, betamethasone sodium phosphate 0.0106 mg / mL, ethanol content by volume ratio 0.2%, sodium chloride 7.5 mg / mL, sodium carboxymethyl cellulose 7.5 mg / mL, sodium hydroxybenzoate 0.3 mg / mL, Tween 80 content by volume ratio 0.2%; the remainder is water for injection.

6. A method for preparing the compound betamethasone nasal wash according to any one of claims 1 to 5, It is characterized in that The steps include: S1: dissolve betamethasone sodium phosphate, sodium chloride, Tween 80 and sodium methylparaben in water for injection, and filter to obtain a filtrate; S2: adding sodium carboxymethyl cellulose to water for injection and heating it to dissolve it, and then mixing it with the filtrate obtained in step S1 to obtain a mixed solution; S3: dissolving betamethasone dipropionate in ethanol, gradually adding the mixed solution obtained in step S2, and grinding evenly by liquid addition grinding method to obtain the compound betamethasone nasal wash.

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