CN117257778A - Comprises pulsatilla root saponin B 4 Is inhaled solution and uses thereof - Google Patents

Comprises pulsatilla root saponin B 4 Is inhaled solution and uses thereof Download PDF

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Publication number
CN117257778A
CN117257778A CN202311555016.4A CN202311555016A CN117257778A CN 117257778 A CN117257778 A CN 117257778A CN 202311555016 A CN202311555016 A CN 202311555016A CN 117257778 A CN117257778 A CN 117257778A
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inhalation solution
inhalation
citric acid
sodium citrate
solution
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金方
薄浩洋
连晓培
高红伟
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Joincare Pharmaceutical Group Industry Co ltd
Guangxi Xinhai Pharmaceutical Technology Co Ltd
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Joincare Pharmaceutical Group Industry Co ltd
Guangxi Xinhai Pharmaceutical Technology Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • Oil, Petroleum & Natural Gas (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
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Abstract

The invention relates to a Chinese pulsatilla root saponin B 4 Is used for inhalation solution and application. The inhalation solution is prepared from active ingredient white head Weng Zaogan B 4 And the auxiliary materials in the inhalation solution comprise osmotic pressure regulator and buffer stabilizer, wherein the buffer stabilizer is citric acid and sodium citrate. The inhalation solution of the invention can effectively reduceLess of the effect of the API itself and environmental factors on the formulation and slows the rate of growth of the relevant substances during storage of the drug. In addition, as the auxiliary material of the inhalation solution is citric acid/sodium citrate, the bad taste of the raw material medicine can be partially masked, so that the inhalation solution has higher patient compliance. The inhalation solution of the application uses less auxiliary materials and has good safety.

Description

Comprises pulsatilla root saponin B 4 Is inhaled solution and uses thereof
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a pharmaceutical composition containing pulsatilla root saponin B 4 Is used for inhalation.
Background
Pulsatilla saponin B 4 Is pentacyclic triterpene saponin extracted from radix Pulsatillae with pharmacological activity, has pharmacological effects of antiinflammatory, antibacterial, immunoregulating, antitumor, antioxidant, antiviral, etc., and has potential for treating asthma and Chronic Obstructive Pulmonary Disease (COPD).
The prior art CN111956655A is prepared from pulsatilla root saponin B 4 Can be made into oral preparation and injection for treating COPD. CN111904970A is prepared from pulsatilla root saponin B 4 The product is poor in stability, however, the content of the spray is reduced by 1.4% -10.0% when the spray is placed for 10 days at a high temperature of 40 ℃, the effective components of the aerosol are obviously decomposed under the illumination condition, and the content of the aerosol is reduced by 2.25% -8.00% when the aerosol is illuminated for 10 days.
The inhalation solution is one of inhalation preparations, and the medicine is dissolved in a solvent and is administrated through an atomization device, so that the inhalation solution has the advantages of quick response, strong targeting and the like.
Pulsatilla saponin B 4 The extract is extracted from the dry roots of the pulsatilla chinensis, and according to different extraction processes, a small amount of residual solvent or other impurities are mixed in the raw material medicine, so that the pH value of the raw material medicine is 4-8. According to the research, pulsatilla chinensis saponin B 4 Unstable, prior art CN114377027 is prepared from pulsatilla saponin B 4 Can be made into aerosol inhalation for treating SARS-COV-2. The pH regulator is hydrochloric acid, acetic acid, sodium hydroxide, sodium carbonate, etc. The prepared liquid medicine is inspected under the conditions of strong illumination and high temperature, the pH value of the liquid medicine is obviously changed, and the impurity is obviously increased. CN113499326B is prepared from pulsatilla root saponin B 4 Making into nanometer preparation for use asTNFR2 and Foxp3 protein inhibitors for use in the treatment of cancer.
Pulsatilla saponin B 4 Has a certain bitter taste, and can affect the compliance of patients when made into inhalation solution.
To date, there is no relatively stable pulsatilla saponin B that can meet patient compliance 4 The preparation is inhaled.
Disclosure of Invention
In order to solve the defects in the prior art, the invention provides a Chinese pulsatilla root saponin B 4 Is used for inhalation. According to the inhalation solution, citric acid/sodium citrate is used as a buffer stabilizer, the concentration is 1.9 mM-19 mM, the influence of an API (application program interface) and environmental factors on a preparation can be effectively reduced, and the growth rate of related substances of a medicament in a storage period is slowed down. In addition, as the auxiliary material of the inhalation solution is citric acid/sodium citrate, the bad taste of the raw material medicine can be partially masked, so that the inhalation solution has higher patient compliance. The inhalation solution of the application uses less auxiliary materials and has good safety.
The above object of the present application is achieved by the following technical solutions.
In one aspect, the present invention provides a pharmaceutical composition comprising pulsatilla root saponin B 4 Is used for preparing medicines for treating and/or preventing asthma and chronic obstructive pulmonary disease,
wherein the inhalation solution is prepared from active ingredient white head Weng Zaogan B 4 And the auxiliary materials in the inhalation solution comprise osmotic pressure regulator and buffer stabilizer, wherein the buffer stabilizer is citric acid and sodium citrate.
Preferably, the total concentration of the citric acid and the sodium citrate in the inhalation solution is 1.9 mM-19 mM.
Preferably, the pH value of the inhalation solution is 5.0-7.0.
Preferably, the osmolality adjusting agent is sodium chloride.
Preferably, the inhalation solution may further comprise a stabilizer, which is disodium edetate.
Preferably, the inhalation solution may further comprise a pH adjuster, the pH adjuster being hydrochloric acid or sodium hydroxide.
In another aspect, the present invention provides a composition comprising pulsatilla saponin B 4 Is inhaled by the active ingredient white head Weng Zaogan B 4 And auxiliary materials. The inhalation solution is one of inhalation preparations, and the medicine is dissolved in a solvent and is administrated through an atomization device, so that the inhalation solution has the advantages of quick response, strong targeting and the like.
Preferably, the auxiliary materials in the inhalation solution comprise an osmotic pressure regulator and a buffer stabilizer.
Preferably, the buffer stabilizer is citric acid and sodium citrate. Citric acid, sodium citrate and the like are common buffer salt pairs in injection, and other common buffer salts comprise phosphate buffer salts and the like. The citric acid used in the invention is an organic acid which is naturally and largely present in plants and can be used as food additives and pharmaceutical excipients. Citric acid is weak acid, and is not completely dissociated in water, and citric acid, citrate and H are simultaneously present in the solution + . Sodium citrate is the sodium salt of citric acid. When the solution is added with citric acid and sodium citrate at the same time, if H + Increase, H + Citric acid is formed with free citrate particles, so that the pH drop of the solution is slowed down; if H in solution + Reduced ionization of citric acid to H + Thereby slowing the rise in pH of the solution.
Preferably, the total concentration of the citric acid and the sodium citrate in the inhalation solution is 1.9 mM-19 mM. The inventors of the present application have unexpectedly found that, by using citric acid and sodium citrate, and controlling the total concentration of citric acid and sodium citrate to be in the range of 1.9 mM-19 mM, in particular, completely different from other buffer systems, the pH of the inhalation solution can be stabilized at 5.0-7.0, and more importantly, impurities and environmental factors in the API (e.g., dissolved CO in a solvent 2 Microorganism multiplication, etc.) on the formulation, so that the drug is stable during storage and the rate of growth of the relevant substances is slowed. Furthermore, the buffer stabilizer citric acid and sodium citrate in the inhalation solution has a certain sour taste and salty taste, and can partially mask the originalBad taste of the drug.
Preferably, the osmotic pressure regulator is selected from sodium chloride and the like, and the sodium chloride is commonly used in solution dosage forms, so that the osmotic pressure regulator has high safety.
Preferably, other auxiliary materials including but not limited to stabilizers, pH regulators and the like can be added to the inhalation solution according to the need.
Preferably, the stabilizer in the inhalation solution is disodium edetate.
Because the liquid preparation devices, pipelines, tank bodies and filling machines adopted in the production of the liquid preparation are all made of stainless steel, metal ions can be introduced to influence the stability of the product. Disodium edetate is a commonly used chelating agent in pharmaceutical formulations and can catalyze autoxidation reactions to remove metal ions from the formulation.
The pH regulator in the inhalation solution is selected from hydrochloric acid, sodium hydroxide, etc., and H can be ionized in water + Or OH (OH) - The pH value of the solution is changed, and the pH regulator is a common pH regulator for liquid preparations.
In yet another aspect, the present invention also provides a product comprising the inhalation solution described above, wherein the inhalation solution is filled in a low density polyethylene bottle and externally packaged using an aluminum foil pouch for aerosol inhalation administration.
The inhalation solutions of the present invention may be filled into low density polyethylene bottles or other packaging forms for aerosol inhalation administration. The outside can use aluminium foil bag packing, reduces the influence of light to medicine stability.
Compared with the prior art, the application has at least the following beneficial technical effects:
the application develops the pulsatilla saponin B on the basis of earlier research 4 The buffer stabilizer is different from the common pH regulator in that the buffer stabilizer not only can effectively reduce the influence of the API and environmental factors on the pH of the preparation, but also can slow down the growth rate of related substances of the medicine during storage.
Detailed Description
Examples 1 to 10
Examples 1 to 10 were prepared according to the following table, and sodium chloride, citric acid/sodium citrate, disodium edentate and pulsatilla saponin B were added to the purified water 4 And then, adjusting the pH value of the prescription to 5.1-7.0 by using hydrochloric acid and sodium hydroxide, wherein the addition amount of citric acid/sodium citrate is 1.9-19 mM.
Example 11Comprises pulsatilla root saponin B 4 Is inhaled into the patient's body
Prescription:
the process comprises the following steps:
dissolving sodium chloride, citric acid and sodium citrate in injectable water, and adding pulsatilla saponin B into the container 4 Stirring was continued to dissolve and finally the solution was filled into LPDE bottles at 2 ml/vial.
The product is atomized by using a jet atomizer, and the atomization rate of the product is measured to be 1.3mg/min according to the rule 0111 of the four general rules of the Chinese pharmacopoeia of 2020 edition, and the total delivery amount is 8.4mg.
Test example 1: pulsatilla saponin B 4 Is tested on long-term cigarette smoke inhalation+LPS-induced rat COPD model
Test drug: the pulsatilla root saponin B prepared in example 11 4 Is inhaled into the patient's body
Test animals: SD rats, 72
Grouping: after animal-adaptive feeding, 72 male SD rats were randomly divided into 6 groups (blank, model, B) 4 Low dose inhalation group, B 4 Medium dose inhalation group, B 4 High dose inhalation group, DEX group).
Model group, B 4 Low dose inhalation group, B 4 Medium dose inhalation group, B 4 High dose inhalation group, DEX group build COPD model：
(1) LPS airway sparging: after the rats are anesthetized, the animals are anesthetized, a non-invasive airway is injected into the LPS, the concentration of the LPS is 5 mg/mL, the dosage is 20 mu L/100g, the first Day of LPS molding is Day 0, then the airway injection is carried out every 4 weeks, and the rats are not exposed to smoke due to anesthesia.
(2) Smoke exposure: the rat is put into the animal smoking device, the box cover is closed, after the cigarette is lighted, the cigarette smoke is pumped into the animal smoking device by a vacuum pump and is filled, so that the rat smoke is exposed. Each cigarette smoke is exposed for 10 min, air is exposed for 10 min, and the next cigarette is carried out. 10 cigarettes per day for 12 weeks. The blank group was exposed to air.
Administration:
(1) The blank group and the model group were administered by aerosol inhalation of physiological saline.
（2）B 4 Low dose inhalation group, B 4 Medium dose inhalation group, B 4 The high dose inhalation groups respectively use atomized inhalation pulsatilla root saponins B 4 Inhalation solution, the dosage is 0.47, 0.94, 1.88 mg/kg respectively;
(3) DEX group model group was intraperitoneally injected with 0.05 mg/mL dexamethasone sodium phosphate, 1mL/100g dose.
Each group was dosed once a day before molding until the end of the trial.
Test results:
the results of the long-term cigarette smoke inhalation+lps-induced rat COPD model show that: b (B) 4 The (0.47, 0.94, 1.88 mg/kg, ih) groups significantly reduced the increase in total white blood cells, with inhibition rates of 35.48%, 35.49%, 46.79% (P)<0.001 A) is provided; classification counting observation shows that the increase of neutrophils in BALF is obviously reduced, and the inhibition rates are 52.98%, 63.58% and 69.92% respectively; obviously reduce the increase of macrophages, and the inhibition rates are 51.46%, 64.35% and 68.35% respectively. Pathological section H&E staining results show, B 4 Both the three dose and DEX groups significantly reduced infiltration of macrophages and neutrophils into lung tissue. Expression of IL-1 beta, TGF-beta 1 and MUC5B mRNA in lung tissue of rats in model group is obviously increased (P)<0.001）；B 4 The three dose groups and the DEX group can obviously inhibit the expression of IL-1 beta mRNA and inhibit the expression of MUC5B and MUC5AC mRNA; there was a trend to inhibit TGF- β1 mRNA expression but no statistical difference. IL-1 beta, IL-8, IL-17, MMP-12, MMP-9, TGF-beta 1, TNF-alpha, MUC5B, MUC5AC protein in lung tissue of model group rats was significantly increased on average (P)<0.001）。B 4 Both the three dose groups and the DEX group significantly reduced the increase in IL-1β, IL-17, MUC5B and MUC5AC protein levels, but had no significant effect on the increase in IL-8, MMP-12, MMP-9, TGF- β1 and TNF- α protein levels. B (B) 4 The results of Masson staining of the pathological section in the medium dose group showed that the collagen deposition of lung tissue was significantly reduced (P)<0.05 No significant effect was seen for the other groups including the DEX group. Pathological section TUNEL staining results show B 4 And DEX both significantly reduced the increase in apoptosis. Pathological section immunohistochemical staining result shows B 4 And DEX can obviously reduce TWIST protein expression in lung tissues of a rat COPD model and increase E-cadherein protein expression in the lung tissues.
Namely, in a long-term cigarette smoke combined LPS-induced rat COPD model, B 4 The (0.47, 0.94 and 1.88 mg/kg) aerosol inhalation administration can obviously reduce the expression of IL-1 beta, IL-17, TNF-alpha, MUC5AC and MUC5B proteins and the expression of IL-1 beta, MUC5AC and MUC5B mRNA in lung tissues, inhibit inflammatory cytoma in BALF, reduce inflammatory cell infiltration of the lung tissues, inhibit apoptosis of lung tissue cells, reduce the expression of Twist in the lung tissues and increase the expression of E-cadherin protein, reduce airway resistance of model rats and improve lung functions, and play a role in relieving COPD symptoms.
Comparative examples 1 to 3
Comparative examples 1 to 3 were prepared according to the following table, and sodium chloride and pulsatilla saponin B were added to purified water 4 No citrate is added, and then the pH value of the prescription is adjusted to 5.2-6.6 by hydrochloric acid and sodium hydroxide.
Comparative examples 4 to 5
Adding different purification processes of pulsatilla root saponin B into purified water 4 No citrate nor sodium chloride was added.
Comparative example 6
Comparative example 6 was prepared according to the following table, and sodium chloride, citric acid/sodium citrate and pulsatilla saponin B were added to purified water 4 Then, the pH value of the prescription is adjusted to 6.0 by hydrochloric acid and sodium hydroxide, and the addition amount of citric acid/sodium citrate is 40mM.
Comparative examples 7 to 8
Comparative example 7 was prepared according to the following table, and sodium chloride, disodium hydrogen phosphate/sodium phosphate and pulsatilla saponin B were added to purified water 4 Then, the pH of the recipe was adjusted to 6.0 with hydrochloric acid and sodium hydroxide, respectively, the addition amount of disodium hydrogen phosphate/sodium phosphate was 3.8mM, and the addition amount of acetic acid/sodium acetate was 13.6mM.
Comparative example 9
Comparative example 9 was prepared according to the following table, and sodium chloride, disodium edentate and pulsatilla saponin B were added to purified water 4 Then, the pH value of the prescription is adjusted to 6.1 by hydrochloric acid and sodium hydroxide, and no citrate is added.
Test example 1
Taking 20mL of the solutions of examples 6, 7 and 8 and comparative examples 2, 4 and 5, dropwise adding 0.1mol/L NaOH or 0.1mol/L HCl until the pH value is more than 9 or less than 4, and recording the dosage of the NaOH solution or the HCl solution.
Test example 2
Examples 1 to 10 and comparative examples 1 to 3 and 6 to 9 were placed at a high temperature of 60℃to examine the pH and the stability of each formulation.
Test example 3
Taking example 11, the pH, content and related substance changes were evaluated by standing at 40℃and 75% RH for 3 months.
Test example 4
The solutions of examples 6 to 9 and comparative example 5 and physiological saline were taken and evaluated for bitterness.
Test example 5
Examples 10 and 11 were filled in LDPE bottles, one part was placed directly under an environment of strong illumination, the other part was sealed with an aluminum bag and placed under an environment of strong illumination, and the other part was placed for 10 days to evaluate changes in pH and related substances.
During production and storage, the inhalation solution is easily influenced by acid and alkali to cause the solution to change, which may influence the stability of the medicine and further influence the safety of the medicine. Test example 1 examples 6 to 8 and comparative examples 2, 4 and 5 were examined for their buffer capacity against acids and bases. The results show that the buffer capacity for acid and base is significantly lower than that of examples 6-8 when only hydrochloric acid and sodium hydroxide are used as pH regulator (comparative example 2) or no pH regulator is added (comparative examples 4, 5), and the buffer capacity for citric acid/sodium citrate decreases with decreasing concentration. Test example 2 stability at 60 c under high temperature conditions was investigated for examples 1 to 10, comparative examples 1 to 3 and comparative examples 6 to 9. The results show that the pH of examples 1-10 is stable when left at 60 ℃ for 10 days, the difference from 0 day is within 0.1, and the total impurity increase of related substances is not more than 0.43%. In comparative examples 1-3, only hydrochloric acid and sodium hydroxide are used as pH regulators, citric acid/sodium citrate is not added, the difference between the pH of 10 days and the pH of 0 day at 60 ℃ is 0.1-1.0, the pH is easily affected by the environment, and the pH is not stable enough; the total impurity increase for related substances at 10 days at high temperature was 0.52%,0.54%,0.61%, comparative example 6 (0.48% for total impurity increase at 10 d) slightly inferior to the concentration of citric acid/sodium citrate of 40mM, and comparative example 7 (0.45% for total impurity increase at 10 d) using phosphate buffer salt and comparative example 8 (0.54% for total impurity increase at 10 d) using acetic acid/sodium acetate buffer salt were significantly inferior to examples 1, 3, and 4 (0.33%, 0.27%, and 0.33% for total impurity increase at 10 d) at near pH, respectively.
The increase in the substances of example 10, in which disodium ethylenediamine tetraacetate was added as a stabilizer and in which citrate was added as a pH adjuster, was identical to that of example 3, in which disodium ethylenediamine tetraacetate was not added as a stabilizer (0.27% increase in total impurities at high temperature 10 d), and was superior to that of comparative example 9, in which citrate was not added as a pH adjuster (0.41% increase in total impurities at high temperature 10 d),
in conclusion, the citric acid/sodium citrate reduces the influence of the environment on the pH of the solution at the concentration of 1.9 mM-19 mM, and the sodium citrate has on the pulsatilla root saponin B 4 Has certain stabilizing effect. When the concentration of the citric acid is too high, the stronger buffering capacity is not significant, but the stability of the effective components is reduced due to the too high salt concentration. The stability of the solution with phosphate buffer salt was slightly inferior to the formulation with citrate buffer salt.
Test example 3 the stability of example 11 at 40 c was investigated. The results show that the pH and content of the product are not obviously changed, the impurity increase is less, the product has stable properties and can resist the high temperature of 40 ℃ after the citric acid/sodium citrate is added in the embodiment 11 and is inspected for 3 months at the temperature of 40 ℃.
Test example 4 study of citric acid/sodium citrate on pulsatilla root saponin B 4 Masking effect of bad taste. The results show that the taste of the citric acid/sodium citrate is masked to a certain extent after the citric acid/sodium citrate is added in examples 6 to 9 4 The bitter taste of comparative example 5 without added citric acid/sodium citrate was reduced.
Test example 5 the light stability of the product was investigated. The results show that the product with 0.01% disodium edetate added (example 10) has a poorer light stability than the product without disodium edetate added (example 11), and that the stability of both products is significantly improved after packaging with aluminum bags.

Claims (11)

1. Comprises pulsatilla root saponin B 4 Is used for preparing medicines for treating and/or preventing asthma and chronic obstructive pulmonary disease,
wherein the inhalation solution is prepared from active ingredient white head Weng Zaogan B 4 And auxiliary materials, wherein the auxiliary materials in the inhalation solution comprise osmotic pressure regulator and buffer stabilizer, the buffer stabilizer is citric acid and sodium citrate,
wherein the total concentration of citric acid and sodium citrate in the inhalation solution is 1.9 mM-19 mM.
2. The use according to claim 1, wherein the pH of the inhalation solution is 5.0-7.0.
3. Use according to claim 1 or 2, characterized in that the osmolality adjusting agent is sodium chloride.
4. Use according to claim 1 or 2, wherein the inhalation solution further comprises a stabilizer which is disodium edetate.
5. Use according to claim 1 or 2, wherein the inhalation solution further comprises a pH regulator, which is hydrochloric acid or sodium hydroxide.
6. Comprises pulsatilla root saponin B 4 The inhalation solution is characterized by comprising an active ingredient white head Weng Zaogan B 4 And auxiliary materials, wherein the auxiliary materials in the inhalation solution comprise osmotic pressure regulator and buffer stabilizer, the buffer stabilizer is citric acid and sodium citrate,
wherein the total concentration of citric acid and sodium citrate in the inhalation solution is 1.9 mM-19 mM.
7. The inhalation solution according to claim 6, wherein the pH of the inhalation solution is 5.0 to 7.0.
8. The inhalation solution according to claim 6 or 7, wherein the osmolality adjusting agent is sodium chloride.
9. The inhalation solution according to claim 6 or 7, further comprising a stabilizer which is disodium edetate.
10. The inhalation solution according to claim 6 or 7, further comprising a pH adjustor which is hydrochloric acid or sodium hydroxide.
11. A product comprising the inhalation solution of any one of claims 6 to 10, wherein the inhalation solution is filled in low density polyethylene bottles, externally packaged with aluminum foil bags, for aerosol inhalation administration.
CN202311555016.4A 2023-11-21 2023-11-21 Comprises pulsatilla root saponin B 4 Is inhaled solution and uses thereof Pending CN117257778A (en)

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CN111904970A (en) * 2020-08-19 2020-11-10 广西馨海药业科技有限公司 Application of pulsatilla chinensis saponin B4 in preparation of medicine for treating asthma

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107320464A (en) * 2017-04-28 2017-11-07 北京北朋科技有限公司 The preparation method of the budesonide suspension of high pH value
CN111904970A (en) * 2020-08-19 2020-11-10 广西馨海药业科技有限公司 Application of pulsatilla chinensis saponin B4 in preparation of medicine for treating asthma

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