Carbazochrome sodium sulfonate inhalation powder and application thereof in local hemostasis

Abstract

The invention relates to carbazochrome sodium sulfonate inhalation powder and application of the carbazochrome sodium sulfonate inhalation powder in local hemostasis, and aims to solve the problems of blood coagulation function influence and adverse reaction caused by existing systemic hemostasis drugs in treatment of patients with cardiovascular diseases. Effective delivery and deposition of the medicine in the lung are ensured, and the local hemostasis effect is achieved. The medicine particles have proper particle size distribution and can be quickly absorbed by the lung after being inhaled, so that the bioavailability is improved. The carbazochrome sodium sulfonate inhalation powder disclosed by the invention can be used for quickly stopping bleeding, reducing the bleeding amount and the bleeding frequency, avoiding the influence on the blood coagulation function of the whole body and reducing the occurrence rate of adverse reactions. Compared with the existing systemic hemostatic drug, the pharmaceutical composition has higher safety and effectiveness, and provides a new treatment choice for bronchiectasis hemoptysis patients, especially patients with cardiovascular diseases.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, in particular to a carbazochrome sodium sulfonate inhalation powder and application thereof in local hemostasis. Background Art

[0002] In clinical practice, bronchiectasis hemoptysis is a common respiratory disease, especially when such patients have cardiovascular diseases, the treatment becomes particularly complicated. Since patients with cardiovascular diseases often need antithrombotic therapy to prevent thrombosis, and hemoptysis requires hemostatic therapy, these two treatment strategies are contradictory to a certain extent. Antithrombotic therapy aims to keep blood flowing and prevent thromboembolism, while hemostatic therapy requires enhancing coagulation function to control bleeding. Therefore, how to effectively control hemoptysis without affecting the antithrombotic effect has become a problem that needs to be solved urgently in clinical practice.

[0003] At present, hemostatic treatment for patients with bronchiectasis and hemoptysis mainly relies on intravenous and oral medications. These drugs are widely distributed in the body and act on the whole body. Although they can control bleeding to a certain extent, they often have a significant impact on coagulation function and increase the risk of thrombosis, which is particularly unfavorable for patients with cardiovascular diseases. In addition, systemic hemostatic drugs may also cause other adverse reactions, such as gastrointestinal discomfort and allergic reactions, further increasing the treatment burden and risks of patients.

[0004] Given the limitations of systemic hemostatic drugs, developing a hemostatic drug that can act locally on the lungs has become a potential solution. Local hemostatic drugs can act directly on the bleeding site, reduce the distribution of the drug in the body, thereby reducing the impact on coagulation function and improving the hemostatic effect. In the treatment of respiratory diseases, inhaled powders have shown unique advantages, such as inhaled drugs such as Symbicort and Dopamine, which are commonly used by COPD patients. They deliver drugs directly to the lungs through an inhalation device, achieving local administration and improving the efficacy and safety of the drugs.

[0005] In summary, for patients with bronchiectasis and hemoptysis, especially those with cardiovascular diseases, the development of an inhaled powder hemostatic drug that can act locally on the lungs is of great clinical significance. Summary of the invention

[0006] In order to solve the problems of the prior art, the present invention provides a carbazochrome sodium sulfonate inhalation powder and its application in local hemostasis. The new drug can not only avoid the adverse reactions caused by systemic hemostatic drugs, but also can quickly enter the blood to play a local hemostatic effect, providing patients with a safer and more effective treatment option.

[0007] In order to solve the above technical problems, the present invention is achieved through the following technical solutions: In the first aspect, a carbazochrome sodium sulfonate inhalation powder comprises:

[0008] Carbazochrome sodium sulfonate, as the main active ingredient in the powder;

[0009] The carrier is set to lactose;

[0010] Stabilizers and dispersants;

[0011] The powder is configured to have a predetermined particle size distribution suitable for pulmonary inhalation, and when inhaled through an inhalation device, can achieve rapid local hemostasis in the lungs.

[0012] In the first aspect, the composition of the sodium carbazochrome sulfonate inhalation powder is

[0013] The role of sodium carbazochrome sulfonate

[0014] As the main active ingredient of the powder, carbazochrome sodium sulfonate is an effective hemostatic drug. It acts on vascular smooth muscle to enhance the contraction of the vascular wall, thereby quickly stopping bleeding. In the case of pulmonary bleeding, carbazochrome sodium sulfonate can quickly act on the bleeding site to achieve local hemostasis.

[0015] Choice of carrier

[0016] Lactose as a carrier not only has good physical stability, but also improves the dispersibility and solubility of powders. The particle size, shape and surface properties of lactose have an important influence on the inhalation efficiency and lung deposition effect of powders. Therefore, when choosing lactose as a carrier, its quality needs to be strictly controlled.

[0017] The role of stabilizers and dispersants

[0018] Stabilizers such as ascorbic acid, ethylenediaminetetraacetic acid or their salts can protect carbazochrome sodium sulfonate from oxidation or other adverse conditions and maintain its activity. Dispersants such as polysorbate 80, lecithin or a combination thereof can improve the dispersibility of the powder and make it easier to be absorbed by the lungs.

[0019] The Importance of Particle Size Distribution

[0020] The particle size distribution of the powder is critical to the inhalation efficiency and lung deposition effect. D50 (median particle size) between 1 and 5 microns and D90 (90% of the particles are smaller than this particle size) not exceeding 10 microns can ensure that the powder can be effectively inhaled into the lungs and deposited at the bleeding site.

[0021] In a specific embodiment of the first aspect, the stabilizer is selected from ascorbic acid, ethylenediaminetetraacetic acid or salts thereof, and the dispersant is selected from polysorbate 80, lecithin or a combination thereof.

[0022] In a specific embodiment of the first aspect, the powder has a particle size distribution of D50 between 1 and 5 microns and D90 not exceeding 10 microns.

[0023] In a specific embodiment of the first aspect, the specific weight of the internal components of the powder is: 2-8 parts of carbazochrome sodium sulfonate, 800-950 parts of carrier, 1-3 parts of stabilizer, and 2-4 parts of dispersant.

[0024] A second aspect is a method for preparing carbazochrome sodium sulfonate inhalation powder, comprising the following steps:

[0025] Step 1: Mix carbazochrome sodium sulfonate, a carrier, a stabilizer and a dispersant in a predetermined ratio;

[0026] Step 2: micronizing the mixture to obtain a particle size distribution suitable for lung inhalation;

[0027] Step 3: Perform quality control testing on the micronized mixture to ensure it meets the specified standards.

[0028] In a second aspect, a method for preparing a sodium carbazochrome sulfonate inhalation powder

[0029] Mixing Steps

[0030] Mix carbazochrome sodium sulfonate, carrier, stabilizer and dispersant in a predetermined ratio to ensure uniform distribution of the ingredients. The mixing time and mixing intensity need to be controlled during the mixing process to avoid overheating or excessive abrasion of the powder.

[0031] Micronization

[0032] The mixture is micronized to obtain a particle size distribution suitable for pulmonary inhalation. The micronization method can be selected from air flow milling, spray drying, etc. During the micronization process, the operating conditions such as temperature, pressure and milling time need to be strictly controlled to ensure the quality and stability of the powder.

[0033] Quality Control Testing

[0034] The micronized mixture is subjected to quality control tests, including particle size distribution test, active ingredient content test, stability test, etc. These tests can ensure that the powder meets the specified standards and has good inhalation efficiency and hemostatic effect.

[0035] In a third aspect, an inhalation device for local hemostasis comprises carbazochrome sodium sulfonate inhalation powder and an inhalation mechanism for effectively delivering the powder to the lungs.

[0036] In a third aspect, an inhalation device for local hemostasis

[0037] Design of suction mechanism

[0038] The design of the inhalation mechanism has an important impact on the inhalation efficiency and hemostatic effect of the powder. A dry powder inhaler is a commonly used inhalation mechanism that uses the patient's inhalation force to disperse and inhale the powder into the lungs. The design of a dry powder inhaler needs to take into account factors such as the physical properties of the powder, the patient's breathing pattern, and the inhalation needs.

[0039] Use and operation of the device

[0040] The inhalation device should be easy to use and operate, and convenient for patients to use independently. At the same time, the device also needs to have good sealing and stability to ensure that the powder is not contaminated or deteriorated during storage and use.

[0041] In a specific embodiment of the third aspect, the inhalation mechanism is a dry powder inhaler, which is designed so that the powder can be effectively dispersed and inhaled into the lungs when the patient inhales.

[0042] A fourth aspect is the use of a sodium carbazochrome sulfonate inhalation powder for local hemostasis, wherein the powder is inhaled into the lungs to achieve rapid hemostasis at the bleeding site.

[0043] In the fourth aspect, the use of carbazochrome sodium sulfonate inhalation powder in local hemostasis

[0044] Indications and therapeutic effects

[0045] Carbazochrome sodium sulfonate inhalation powder is mainly used to treat patients with bronchiectasis and hemoptysis, especially those with cardiovascular diseases who need antithrombotic treatment. By inhaling the powder, bleeding can be stopped quickly, relieving the patient's symptoms and pain. At the same time, since the powder acts directly on the bleeding site, the side effects and risks of systemic medication can be reduced.

[0046] Usage and precautions

[0047] When using carbazochrome sodium sulfonate inhalation powder, you need to follow the instructions or doctor's advice. Patients should understand the usage and precautions under the guidance of a doctor, such as preparation before inhalation, breathing control during inhalation, etc. At the same time, patients also need to pay attention to their own symptoms and reactions, and seek medical attention immediately if they feel uncomfortable.

[0048] In a specific embodiment of the fourth aspect, it is used to treat patients with bronchiectasis and hemoptysis, especially patients with combined cardiovascular diseases who need antithrombotic treatment.

[0049] The beneficial effects of the present invention are:

[0050] 1. The present invention directly acts on the bleeding site of the lung, achieving rapid and effective local hemostasis, significantly shortening the hemostasis time and alleviating the patient's pain. Compared with the traditional systemic medication method, the inhaled powder can directly deliver the drug to the lesion, reducing the distribution and metabolism of the drug in the body, thereby reducing the side effects and risks that may be caused by systemic medication;

[0051] 2. Carbazochrome sodium sulfonate inhalation powder is not only suitable for patients with bronchiectasis and hemoptysis, but can also be used for patients with other respiratory diseases that require local hemostasis, such as hemoptysis due to tuberculosis and lung cancer. By quickly stopping hemorrhage and reducing the side effects of systemic medication, carbazochrome sodium sulfonate inhalation powder can significantly improve the quality of life of patients and reduce their psychological and economic burdens. DETAILED DESCRIPTION

[0052] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0053] Example 1: Example 1: Preparation and application of sodium carbazochrome sulfonate inhalation powder Preparation steps:

[0054] Raw materials preparation:

[0055] Carbazochrome sodium sulfonate: Select API with purity higher than 98% to ensure drug activity.

[0056] Carrier (lactose): Microcrystalline lactose is selected, which has good fluidity and dispersibility, and the particle size is controlled within an appropriate range.

[0057] Stabilizer: Ascorbic acid is selected because it has antioxidant properties and can effectively protect sodium carbazochrome sulfonate from oxidative degradation.

[0058] Dispersant: Polysorbate 80 can significantly improve the wettability and dispersibility of the powder.

[0059] Accurate weighing:

[0060] According to the formula ratio, accurately weigh 2.5 g of carbazochrome sodium sulfonate, 900 g of lactose, 2 g of ascorbic acid, and 803 g of polysorbate.

[0061] Mix well:

[0062] Place the weighed raw materials in a mixer and mix at an appropriate speed and time to ensure that the components are evenly distributed.

[0063] Micronization treatment:

[0064] The mixture was micronized using a jet mill, and the operating parameters were adjusted to obtain a particle size distribution with a D50 between 2 and 3 microns and a D90 not exceeding 8 microns.

[0065] Quality Control:

[0066] The micronized powder is subjected to particle size distribution test, content uniformity test, microbial limit test, etc. to ensure that the product meets the quality standards.

[0067] Packaging and storage:

[0068] The qualified powder is packed into a special dry powder inhaler capsule, each capsule contains 0.2 mg of carbazochrome sodium sulfonate, and stored in a sealed manner to avoid moisture and contamination.

[0069] Application examples:

[0070] Patient information: Male, 65 years old, bronchiectasis and hemoptysis, complicated by cardiovascular disease, requiring antithrombotic treatment.

[0071] Usage: Under the guidance of a doctor, the patient uses a dry powder inhaler to inhale the sodium carbazochrome sulfonate powder into the lungs, twice a day, one capsule each time.

[0072] Treatment effect: After one week of treatment, the patient's hemoptysis symptoms were significantly alleviated, pulmonary bleeding was effectively controlled, and no adverse reactions occurred.

[0073] Example 2: Optimized preparation and clinical application of carbazochrome sodium sulfonate inhalation powder:

[0074] Raw material optimization:

[0075] Carbazochrome sodium sulfonate: Maintains high purity requirements, but uses more advanced preparation technology to improve drug solubility and bioavailability.

[0076] Carrier (lactose): Lactose prepared by spray drying has better fluidity and more uniform particle size distribution.

[0077] Stabilizer: Add sodium ethylenediaminetetraacetate as an auxiliary stabilizer to further enhance the stability of the drug.

[0078] Dispersants: Lecithin and polysorbate 80 are used in combination to optimize the dispersibility and wetting properties of the powder.

[0079] Accurate weighing:

[0080] According to the optimized formula ratio, accurately weigh 5g of sodium carbazochrome sulfonate, 850g of lactose, 1.5g of ascorbic acid, 0.5g of sodium edetate, 2.5g of lecithin, and 1.5g of polysorbate 80.

[0081] Mixing and Micronization:

[0082] A high-speed mixer is used for mixing to ensure uniform distribution of the components; micronization is then performed to obtain a particle size distribution with a D50 between 1.5 and 2.5 microns and a D90 not exceeding 9 microns.

[0083] Quality Control and Packaging:

[0084] Strict quality control tests are carried out, including content determination, particle size analysis, microbiological inspection, etc.; once qualified, the powder is loaded into a dedicated dry powder inhaler and attached with detailed instructions for use.

[0085] Clinical application examples:

[0086] Patient information: Female, 50 years old, with a history of bronchiectasis and hemoptysis for many years. Her condition has worsened recently and she needs emergency hemostatic treatment.

[0087] Treatment: In the emergency room, doctors used an optimized inhalation powder of carbazochrome sodium sulfonate to treat the patient, which is delivered directly into the lungs via a dry powder inhaler.

[0088] Treatment effect: After treatment, the patient's hemoptysis symptoms were quickly relieved and pulmonary bleeding was effectively controlled. Subsequently, the patient continued to use inhalation powder for consolidation treatment as prescribed by the doctor, and his condition stabilized without recurrence of hemoptysis.

[0089] The above two examples show the preparation process of carbazochrome sodium sulfonate inhalation powder and its clinical application effect. By optimizing the selection of raw materials, preparation process and formulation ratio, the efficacy and safety of the drug can be further improved to meet the treatment needs of patients.

[0090] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A carbazochrome sodium sulfonate inhalation powder, characterized in that, include: Carbazochrome sodium sulfonate, as the main active ingredient in the powder; The carrier is set to lactose; Stabilizers and dispersants; The powder is configured to have a predetermined particle size distribution suitable for pulmonary inhalation, and when inhaled through an inhalation device, can achieve rapid local hemostasis in the lungs.

2. A carbazochrome sodium sulfonate inhalation powder according to claim 1, characterized in that: The stabilizer is selected from ascorbic acid, ethylenediaminetetraacetic acid or salts thereof, and the dispersant is selected from polysorbate 80, lecithin or a combination thereof.

3. A carbazochrome sodium sulfonate inhalation powder according to claim 1, characterized in that: The particle size distribution of the powder is such that D50 is between 1 and 5 microns, and D90 is not more than 10 microns.

4. A carbazochrome sodium sulfonate inhalation powder according to claim 1, characterized in that: The specific weight of the internal components of the powder is: 2-8 parts of carbazochrome sodium sulfonate, 800-950 parts of carrier, 1-3 parts of stabilizer, and 2-4 parts of dispersant.

5. A method for preparing the carbazochrome sodium sulfonate inhalation powder according to any one of claims 1 to 4, characterized in that: The following steps are involved: Step 1: Mix carbazochrome sodium sulfonate, a carrier, a stabilizer and a dispersant in a predetermined ratio; Step 2: micronizing the mixture to obtain a particle size distribution suitable for lung inhalation; Step 3: Perform quality control testing on the micronized mixture to ensure it meets the specified standards.

6. An inhalation device for local hemostasis, characterized in that: The invention relates to a method for preparing a sodium carbazochrome sulfonate inhalation powder according to any one of claims 1 to 4, and an inhalation mechanism for effectively delivering the powder to the lungs.

7. The inhalation device for local hemostasis according to claim 6, characterized in that: The inhalation mechanism is a dry powder inhaler, which is designed so that when the patient inhales, the powder can be effectively dispersed and inhaled into the lungs.

8. An application of carbazochrome sodium sulfonate inhalation powder in local hemostasis, characterized in that: The powder is inhaled into the lungs to achieve rapid hemostasis at the bleeding site.

9. The use of a carbazochrome sodium sulfonate inhalation powder according to claim 8 in local hemostasis, characterized in that: Used to treat patients with bronchiectasis and hemoptysis, especially those with concurrent cardiovascular disease who require antithrombotic therapy.