Pharmaceutical composition for treating alveolar echinococcosis and preparation method thereof
Through compositions of albendazole, nelfinavir and other components, sustained release microspheres are formed, which solves the problems of limited efficacy and low bioavailability of vesicular hydatosis drugs, and achieves stable release and long-term treatment of drugs.
Patent Information
- Application Number
- CN202511036017.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-26
- Publication Date
- 2025-09-02
AI Technical Summary
The current drugs for treating vesicular hydatosis are limited in efficacy, rely on host immune function, have extremely low bioavailability and lack of sustained release performance, resulting in unstable frequent drug administration and therapeutic effects.
Using compositions of albendazole, nelfinavir, polylactic acid-glycolic acid copolymer (PLGA), chitosan, sodium cholate, vitamin E succinate and lactose, the sustained release microspheres are formed and tableted through eutectic and sustained release systems to enhance drug penetration and stability.
It improves the bioavailability and therapeutic effect of the drug, reduces the frequency of administration, enhances the stability of the drug in an acidic environment, and extends the validity period to 24 months.
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Figure CN120570897A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of alveolar echinococcosis treatment, and in particular to a pharmaceutical composition for treating alveolar echinococcosis and a preparation method thereof. Background Art
[0002] Alveolar echinococcosis is a fatal parasitic disease caused by the larvae (alveolar cysts) of the tapeworm Echinococcus multilocularis that parasitize humans. Due to the invasive growth of alveolar cysts and their biological characteristics similar to malignant tumors, it is also called "worm cancer." It is mainly transmitted through contact with food, water or the environment contaminated by the feces of the definitive host (canines). After the larvae enter the human body through the mouth, they mostly parasitize the liver (accounting for more than 90%) and can also metastasize to organs such as the lungs and brain. There are often no obvious symptoms in the early stages. In the later stages, due to the continuous destruction of tissues by the worms, liver pain, jaundice, cirrhosis and even liver failure may occur, which can be life-threatening in severe cases. The disease has a long course and progresses insidiously. Drug treatment requires long-term maintenance and traditional preparations have low bioavailability. Surgical resection is difficult. It is a serious public health problem worldwide, especially in agricultural and pastoral areas.
[0003] Currently, the drugs used to treat alveolar echinococcosis are mainly benzimidazoles (such as albendazole and mebendazole), but the oral bioavailability of albendazole is less than 5%, and even when combined with a high-fat diet, it only increases to 15%. Its poor water solubility (<0.1μg / mL) leads to unstable blood drug concentrations, making it difficult to maintain effective therapeutic levels. Mebendazole also has the problem of incomplete absorption and requires multiple doses. Moreover, albendazole is a first-line clinical drug, but its effect depends on the host's T cell immune function. Because alveolar echinococcosis can induce host immunosuppression and is often co-infected with immunodeficiency pathogens such as HIV, the drug's effect is significantly weakened in the immunosuppressive state. For example, studies have shown that the efficacy of albendazole in immunocompromised hosts is significantly lower than that in immune-normal individuals, and the 10-year mortality rate of patients with alveolar echinococcosis exceeds 90%.
[0004] At the same time, most existing preparations are immediate-release and require frequent administration to maintain blood drug concentrations. For example, albendazole has a half-life of only 8.5-10.5 hours and needs to be taken twice a day.
[0005] Therefore, it is necessary to design a pharmaceutical composition for treating alveolar echinococcosis to solve the problems that traditional drugs for treating alveolar echinococcosis have limited efficacy and rely on host immunity, extremely low bioavailability and lack of sustained-release properties. Summary of the Invention
[0006] In view of this, the present invention proposes a pharmaceutical composition for treating alveolar echinococcosis, which is used to solve the problems that traditional drugs for treating alveolar echinococcosis have limited efficacy and rely on host immunity, extremely low bioavailability and lack of sustained-release properties.
[0007] In one aspect, the present invention provides a pharmaceutical composition for treating alveolar echinococcosis, comprising the following components in parts by weight:
[0008] 5-15 parts of albendazole, 2-8 parts of nelfinavir, 30-50 parts of polylactic-co-glycolic acid (PLGA), 5-15 parts of chitosan, 3-8 parts of sodium cholate, 1-3 parts of vitamin E succinate, 20-35 parts of lactose, and 0.5-2 parts of magnesium stearate
[0009] On the other hand, the present invention also provides a method for preparing a pharmaceutical composition for treating alveolar echinococcosis, comprising the following preparation steps:
[0010] Add albendazole and sodium cholate to ethanol, stir until dissolved, cool and stand for crystallization, collect the crystals, and vacuum dry to obtain eutectic powder;
[0011] The polylactic acid-glycolic acid copolymer and chitosan are dissolved in a dichloromethane-acetic acid mixed solvent and stirred to form an organic phase, and then the cocrystal powder and nelfinavir are added and ultrasonically dispersed to form an oil phase, and the oil phase is dropped into a polyvinyl alcohol aqueous solution and magnetically stirred to form a W / O type emulsion, and the stirring speed is reduced to volatilize the dichloromethane. After the end, centrifugation is performed, and the precipitate is collected and freeze-dried to obtain sustained-release microspheres;
[0012] The sustained-release microspheres are mixed with vitamin E succinate and lactose, and then sieved. Magnesium stearate is added for total mixing, and then tableting is performed to obtain the pharmaceutical composition for treating alveolar echinococcosis.
[0013] Furthermore, the temperature of the cooling and standing crystallization is 0-4°C, and the standing time is 12 hours.
[0014] Furthermore, the vacuum drying temperature is 50° C. and the drying time is 8 hours.
[0015] Furthermore, the volume ratio of dichloromethane to acetic acid in the dichloromethane-acetic acid mixed solvent is 3:1.
[0016] Furthermore, the power of the ultrasonic dispersion is 300W, and the ultrasonic time is 5 minutes.
[0017] Furthermore, the rotation speed of the magnetic stirring is 800 rpm, and the stirring time is 30 minutes.
[0018] Furthermore, the centrifugal speed is 3000 rpm and the centrifugal time is 10 minutes.
[0019] Furthermore, the freeze-drying temperature is -50°C and the drying time is 12 hours.
[0020] Furthermore, the tableting pressure is 35KN.
[0021] Compared with the prior art, the present invention has the following beneficial effects:
[0022] 1. The pharmaceutical composition of the present invention uses albendazole and nelfinavir as main active ingredients. Albendazole can inhibit the synthesis of microtubules in the parasite, while nelfinavir is an anti-HIV protease inhibitor that can assist albendazole in penetrating the hydatid cyst wall. This addresses the key problem that the alveolar hydatid cyst wall is dense and contains a large amount of collagen and glycoprotein, making it difficult for drugs to penetrate. By combining the two drugs, the penetrability is enhanced, thus solving the problem that the efficacy of albendazole is limited and depends on the host's immunity.
[0023] 2. In the preparation method of the present invention, albendazole and sodium cholate form a cocrystal, thereby effectively improving its dissolution behavior; at the same time, vitamin E succinate acts as an antioxidant, which can reduce the oxidative degradation of albendazole in an acidic environment and synergize with the PLGA-chitosan sustained-release system to ensure drug stability. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Various other advantages and benefits will become apparent to those skilled in the art upon reading the detailed description of the preferred embodiment below. The accompanying drawings are for illustration purposes only and are not to be considered as limiting the present invention. The same reference symbols are used throughout the drawings to represent the same components. In the drawings:
[0025] Figure 1 The present invention provides a flow chart of a method for preparing a pharmaceutical composition for treating alveolar echinococcosis according to an embodiment of the present invention. DETAILED DESCRIPTION
[0026] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.
[0027] In the description of this application, it should be understood that the terms "center", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on this application.
[0028] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of the technical features being referred to. Thus, a feature specified as "first" or "second" may explicitly or implicitly include one or more of such features. Throughout this application, unless otherwise specified, "plurality" means two or more.
[0029] In the description of this application, it should be noted that, unless otherwise expressly specified or limited, the terms "mounted," "connected," and "connected" should be understood in a broad sense. For example, they can refer to fixed, detachable, or integral connections; mechanical or electrical connections; direct or indirect connections through an intermediate medium; and internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in this application based on the specific circumstances.
[0030] Currently, the drugs used to treat alveolar echinococcosis are mainly benzimidazoles (such as albendazole and mebendazole), but the oral bioavailability of albendazole is less than 5%, and even when combined with a high-fat diet, it only increases to 15%. Its water solubility is poor (<0.1μg / mL), which leads to unstable blood drug concentrations and difficulty in maintaining effective therapeutic levels. Mebendazole also has the problem of incomplete absorption and requires multiple doses; and albendazole is a first-line clinical drug, but its effect depends on the host T cell immune function. Since alveolar echinococcosis can induce host immunosuppression and is often co-infected with immunodeficiency pathogens such as HIV, the effect of the drug is significantly weakened in the immunosuppressive state. For example, studies have shown that the efficacy of albendazole on immunodeficient hosts is significantly lower than that on immune-normal individuals, and the 10-year mortality rate of patients with alveolar echinococcosis exceeds 90%. At the same time, most existing preparations are rapid-release and require frequent administration to maintain blood drug concentrations. For example, the half-life of albendazole is only 8.5-10.5 hours, and it needs to be taken twice a day.
[0031] Therefore, it is necessary to design a pharmaceutical composition for treating alveolar echinococcosis to solve the problems that traditional drugs for treating alveolar echinococcosis have limited efficacy and rely on host immunity, extremely low bioavailability and lack of sustained-release properties.
[0032] On the one hand, in some embodiments of the present application, a pharmaceutical composition for treating alveolar echinococcosis comprises the following components in parts by weight:
[0033] 5-15 parts of albendazole, 2-8 parts of nelfinavir, 30-50 parts of polylactic acid-glycolic acid copolymer, 5-15 parts of chitosan, 3-8 parts of sodium cholate, 1-3 parts of vitamin E succinate, 20-35 parts of lactose, and 0.5-2 parts of magnesium stearate.
[0034] Preferably, the composition comprises 10 parts of albendazole, 5 parts of nelfinavir, 40 parts of polylactic acid-co-glycolic acid copolymer, 10 parts of chitosan, 5 parts of sodium cholate, 2 parts of vitamin E succinate, 25 parts of lactose, and 1 part of magnesium stearate.
[0035] As can be understood, the pharmaceutical composition of the invention contains albendazole and nelfinavir as its main active ingredients. Albendazole inhibits tubulin synthesis in parasites, while nelfinavir is a protease inhibitor against HIV. This combination of drugs can help albendazole penetrate the hydatid cyst wall. This combination addresses the key issue of the dense, collagen- and glycoprotein-rich walls of alveolar hydatid cysts, making them difficult for drugs to penetrate. This enhanced penetration overcomes the limited efficacy of albendazole and its dependence on host immunity.
[0036] It is understandable that PLGA (polylactic-co-glycolic acid) is an FDA-approved biodegradable material with a low molecular weight (5000-10000 Da) that can achieve 12-hour sustained release by regulating the degradation rate, meeting the need to reduce the frequency of dosing;
[0037] It is understandable that the mucosal adhesion of chitosan (deacetylation degree ≥ 90%) can prolong the retention time of the preparation in the intestine, and when combined with PLGA, it forms a dual controlled release mechanism of "skeleton sustained release + adhesion retention".
[0038] It is understandable that lactose as a filler can improve the fluidity of the microspheres, and magnesium stearate as a lubricant can reduce the sticking problem during tableting.
[0039] On the other hand, Figure 1 As shown, in some embodiments of the present application, a method for preparing a pharmaceutical composition for treating alveolar echinococcosis comprises the following preparation steps:
[0040] Add albendazole and sodium cholate to ethanol, stir until dissolved, cool and stand for crystallization, collect the crystals, and vacuum dry to obtain eutectic powder;
[0041] The polylactic acid-glycolic acid copolymer and chitosan are dissolved in a dichloromethane-acetic acid mixed solvent and stirred to form an organic phase, and then the cocrystal powder and nelfinavir are added and ultrasonically dispersed to form an oil phase, and the oil phase is dropped into a polyvinyl alcohol aqueous solution and magnetically stirred to form a W / O type emulsion, and the stirring speed is reduced to volatilize the dichloromethane. After the end, centrifugation is performed, and the precipitate is collected and freeze-dried to obtain sustained-release microspheres;
[0042] The sustained-release microspheres are mixed with vitamin E succinate and lactose, and then sieved. Magnesium stearate is added for total mixing, and then tableting is performed to obtain the pharmaceutical composition for treating alveolar echinococcosis.
[0043] Specifically, albendazole and sodium cholate were added to ethanol and stirred until dissolved at a stirring temperature of 60°C.
[0044] Specifically, the ethanol is anhydrous ethanol, and the mass of the anhydrous ethanol is 50 times the total mass of albendazole and sodium cholate.
[0045] Specifically, the mass of the dichloromethane-acetic acid mixed solvent is 10 times the total mass of the polylactic acid-glycolic acid copolymer and chitosan.
[0046] Specifically, the deacetylation degree of the chitosan is ≥90%, the volume fraction of the polyvinyl alcohol aqueous solution is 1%, and the mass of the polyvinyl alcohol aqueous solution is 5 times that of the oil phase.
[0047] Specifically, the mesh size of the sieve during the sieving is 80 meshes, and the mixing time of the total mixing is 10 minutes.
[0048] It is understood that the preparation method of the present invention effectively improves the dissolution behavior of albendazole by forming a cocrystal with sodium cholate; at the same time, vitamin E succinate acts as an antioxidant, which can reduce the oxidative degradation of albendazole in an acidic environment and synergize with the PLGA-chitosan sustained-release system to ensure drug stability.
[0049] In some embodiments of the present application, the temperature for cooling and standing for crystallization is 0-4°C, and the standing time is 12 hours.
[0050] Specifically, the temperature can be kept between 0-4°C during cooling and standing for crystallization.
[0051] It can be understood that cooling to 0-4°C and standing for 12 hours for crystallization is to reduce the solubility of albendazole and sodium cholate in ethanol in a low temperature environment, prompting the two to precipitate in an orderly manner in a specific proportion and form a stable eutectic structure; long-term standing ensures sufficient crystal growth, reduces impurity inclusion, and improves the purity and uniformity of the eutectic, ultimately obtaining a eutectic powder with significantly improved water solubility (to 7.2 μg / mL), laying the foundation for efficient dissolution and absorption of the drug in subsequent preparations.
[0052] In some embodiments of the present application, the vacuum drying temperature is 50° C. and the drying time is 8 hours.
[0053] It can be understood that the role of air drying (40°C, 8 hours) is to lower the boiling point of ethanol through a negative pressure environment, quickly remove the residual ethanol solvent in the eutectic crystals at a mild temperature (40°C), and avoid high temperature-induced structural destruction of albendazole or sodium cholate and changes in the eutectic morphology; at the same time, the 8-hour drying time can ensure that the crystal water content is ≤0.5%, obtain a eutectic powder with good fluidity and high purity, reduce phase separation or microsphere structural defects caused by solvent residues in the subsequent preparation of sustained-release microspheres, and ensure the stability of the preparation and drug release performance.
[0054] In some embodiments of the present application, the volume ratio of dichloromethane to acetic acid in the dichloromethane-acetic acid mixed solvent is 3:1.
[0055] It can be understood that the present invention utilizes the good solubility of dichloromethane for hydrophobic PLGA and the polar environment of acetic acid to promote the dissolution of chitosan (a hydrophilic polysaccharide containing amino groups), and balances the solubility of the two phases through a 3:1 ratio, so that PLGA and chitosan form a uniform and stable organic phase; at the same time, the polarity and viscosity of the mixed system are moderate, which can ensure the uniform dispersion of the subsequently added albendazole-sodium cholate cocrystal and nelfinavir, provide a suitable medium for the stable formation of the W / O emulsion, avoid uneven microsphere structure or decreased drug encapsulation rate due to incomplete dissolution of the polymer, and ensure the drug loading efficiency and structural integrity of the sustained-release microspheres.
[0056] In some embodiments of the present application, the ultrasonic dispersion power is 300W and the ultrasonic time is 5 minutes.
[0057] It can be understood that the high-frequency mechanical vibration and cavitation effect generated by the 300W ultrasonic power can break the cohesion between the albendazole-sodium cholate cocrystal and the nelfinavir particles, so that they are evenly dispersed in the PLGA-chitosan organic phase to form a suspension system with uniform particle size (<5μm); at the same time, the 5-minute duration can ensure sufficient dispersion while avoiding structural degradation of the drug due to excessive ultrasound, laying the foundation for uniform encapsulation of the drug in the subsequent emulsion preparation, reducing local drug concentration fluctuations caused by uneven drug loading in the microspheres, and ensuring the stability and consistency of drug release from the sustained-release microspheres in the body.
[0058] In some embodiments of the present application, the rotation speed of the magnetic stirring is 800 rpm, and the stirring time is 30 minutes.
[0059] Specifically, the oil phase was dropped into the polyvinyl alcohol aqueous solution and magnetically stirred at 800 rpm for 30 minutes to form a W / O emulsion. The stirring speed was reduced to 300 rpm and stirred for 4 hours to fully volatilize the dichloromethane.
[0060] In some embodiments of the present application, the post-processing specifically comprises: crushing the gel product into particles, freeze-drying and then sieving.
[0061] In some embodiments of the present application, the centrifugal speed is 3000 rpm and the centrifugal time is 10 minutes.
[0062] It is understandable that the PLGA-chitosan sustained-release microspheres are rapidly sedimented by appropriate centrifugal force (3000 rpm), effectively separating the residual polyvinyl alcohol aqueous solution (aqueous phase) in the emulsion and removing unencapsulated drugs and free excipients. The 10-minute centrifugation time ensures complete sedimentation of the microspheres, while avoiding microsphere extrusion deformation or structural damage caused by excessively high speeds (such as >4000 rpm), and also preventing incomplete separation caused by too low speeds (such as <2000 rpm). Ultimately, microspheres with high purity, complete morphology, and uniform particle size distribution are obtained, providing a stable quality intermediate for subsequent freeze-drying and formulation molding, ensuring consistency in drug encapsulation rate and sustained-release performance.
[0063] In some embodiments of the present application, the freeze-drying temperature is -50°C and the drying time is 12 hours.
[0064] It can be understood that by rapidly freezing the PLGA-chitosan microspheres collected by centrifugation at ultra-low temperature (-50°C), the damage to the porous structure of the microspheres caused by the slow growth of ice crystals is avoided, and the ice crystals are sublimated to remove moisture under a vacuum environment. The 12-hour duration can ensure that the moisture content of the microspheres drops below 0.3%; this process can retain the spherical morphology and uniform particle size of the microspheres (avoid agglomeration), maintain their internal network pore structure to ensure the subsequent drug sustained-release performance, and the low temperature condition can prevent PLGA degradation and high-temperature inactivation of albendazole and nelfinavir, and finally obtain a dry, loose, and well-flowing microsphere powder, which is convenient for subsequent mixing with excipients and long-term storage (the shelf life is extended to 24 months).
[0065] In some embodiments of the present application, the tableting pressure is 35KN.
[0066] Specifically, a rotary tablet press is used to compress the tablets at a pressure of 35 KN, and the diameter of the tablets is 8 mm.
[0067] Example 1
[0068] S1. Add 5 parts of albendazole and 3 parts of sodium cholate to 400 parts of anhydrous ethanol, stir at 60°C until completely dissolved, then lower the temperature and maintain it between 0-4°C, let it stand for 12 hours, filter and collect the crystals, and then vacuum dry at 40°C for 8 hours to obtain a eutectic powder;
[0069] S2, dissolving 30 parts of poly(lactic acid-co-glycolic acid) and 5 parts of chitosan in 450 parts of a dichloromethane-acetic acid mixed solvent, stirring until a uniform organic phase is formed, adding the cocrystal powder and 2 parts of nelfinavir to the organic phase, ultrasonicating at a power of 300 W for 5 minutes to form an oil phase, dropping 5 times the mass of the oil phase into a 1% volume fraction aqueous solution of polyvinyl alcohol, stirring at a speed of 800 rpm for 30 minutes to form a W / O type emulsion, reducing the stirring speed to 300 rpm, stirring for 4 hours to volatilize the dichloromethane, and then centrifuging at a speed of 3000 rpm for 10 minutes, collecting the precipitate, and drying at -50°C for 12 hours to obtain sustained-release microspheres;
[0070] S3. Mix the sustained-release microspheres with 1 part of vitamin E succinate and 20 parts of lactose, pass through an 80-mesh sieve, add 0.5 parts of magnesium stearate, and mix for 10 minutes. After the mixture is mixed, a rotary tablet press is used to compress the mixture at a pressure of 35 kN to obtain the pharmaceutical composition for treating alveolar echinococcosis.
[0071] Example 2
[0072] S1. Add 10 parts of albendazole and 5 parts of sodium cholate to 400 parts of anhydrous ethanol, stir at 60°C until completely dissolved, then lower the temperature and maintain it between 0-4°C, let it stand for 12 hours, filter and collect the crystals, and then vacuum dry at 40°C for 8 hours to obtain a eutectic powder;
[0073] S2, dissolving 40 parts of poly(lactic acid-co-glycolic acid) and 10 parts of chitosan in 450 parts of a dichloromethane-acetic acid mixed solvent, stirring until a uniform organic phase is formed, adding the cocrystal powder and 5 parts of nelfinavir to the organic phase, ultrasonicating at a power of 300 W for 5 minutes to form an oil phase, dropping 5 times the mass of the oil phase into a 1% volume fraction aqueous solution of polyvinyl alcohol, stirring at a speed of 800 rpm for 30 minutes to form a W / O type emulsion, reducing the stirring speed to 300 rpm, stirring for 4 hours to volatilize the dichloromethane, and then centrifuging at a speed of 3000 rpm for 10 minutes, collecting the precipitate, and drying at -50°C for 12 hours to obtain sustained-release microspheres;
[0074] S3. Mix the sustained-release microspheres with 2 parts of vitamin E succinate and 25 parts of lactose, pass through an 80-mesh sieve, add 1 part of magnesium stearate, and mix for 10 minutes. After the mixture is mixed, a rotary tablet press is used to compress the mixture at a pressure of 35 kN to obtain the pharmaceutical composition for treating alveolar echinococcosis.
[0075] Example 3
[0076] S1. Add 15 parts of albendazole and 8 parts of sodium cholate to 400 parts of anhydrous ethanol, stir at 60°C until completely dissolved, then lower the temperature and maintain it between 0-4°C, let it stand for 12 hours, filter and collect the crystals, and then vacuum dry at 40°C for 8 hours to obtain a eutectic powder;
[0077] S2, dissolving 50 parts of poly(lactic acid-co-glycolic acid) and 15 parts of chitosan in 450 parts of a dichloromethane-acetic acid mixed solvent, stirring until a uniform organic phase is formed, adding the cocrystal powder and 8 parts of nelfinavir to the organic phase, ultrasonicating at a power of 300 W for 5 minutes to form an oil phase, dropping 5 times the mass of the oil phase into a 1% volume fraction aqueous solution of polyvinyl alcohol, stirring at a speed of 800 rpm for 30 minutes to form a W / O type emulsion, reducing the stirring speed to 300 rpm, stirring for 4 hours to volatilize the dichloromethane, and then centrifuging at a speed of 3000 rpm for 10 minutes, collecting the precipitate, and drying at -50°C for 12 hours to obtain sustained-release microspheres;
[0078] S3. Mix the sustained-release microspheres with 3 parts of vitamin E succinate and 35 parts of lactose, pass through an 80-mesh sieve, add 2 parts of magnesium stearate, and mix for 10 minutes. After the mixture is mixed, a rotary tablet press is used to compress the mixture at a pressure of 35 kN to obtain the pharmaceutical composition for treating alveolar echinococcosis.
[0079] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.
Claims
1. A pharmaceutical composition for treating alveolar echinococcosis, characterized in that: The composition includes the following parts by weight: 5-15 parts of albendazole, 2-8 parts of nelfinavir, 30-50 parts of polylactic acid-glycolic acid copolymer, 5-15 parts of chitosan, 3-8 parts of sodium cholate, 1-3 parts of vitamin E succinate, 20-35 parts of lactose, and 0.5-2 parts of magnesium stearate.
2. A method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 1, characterized in that: The method comprises the following preparation steps: Add albendazole and sodium cholate to ethanol, stir until dissolved, cool and stand for crystallization, collect the crystals, and vacuum dry to obtain eutectic powder; The polylactic acid-glycolic acid copolymer and chitosan are dissolved in a dichloromethane-acetic acid mixed solvent and stirred to form an organic phase, and then the cocrystal powder and nelfinavir are added and ultrasonically dispersed to form an oil phase, and the oil phase is dropped into a polyvinyl alcohol aqueous solution and magnetically stirred to form a W / O type emulsion, and the stirring speed is reduced to volatilize the dichloromethane. After the end, centrifugation is performed, and the precipitate is collected and freeze-dried to obtain sustained-release microspheres; The sustained-release microspheres are mixed with vitamin E succinate and lactose, and then sieved. Magnesium stearate is added for total mixing, and then tableting is performed to obtain the pharmaceutical composition for treating alveolar echinococcosis.
3. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 2, wherein: The temperature of the cooling and standing crystallization is 0-4°C, and the standing time is 12 hours.
4. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 3, wherein: The vacuum drying temperature is 50° C. and the drying time is 8 hours.
5. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 4, wherein: The volume ratio of dichloromethane to acetic acid in the dichloromethane-acetic acid mixed solvent is 3:
1.
6. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 5, characterized in that: The power of the ultrasonic dispersion is 300W, and the ultrasonic time is 5 minutes.
7. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 6, wherein: The magnetic stirring speed is 800 rpm, and the stirring time is 30 minutes.
8. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 7, characterized in that: The centrifugal speed is 3000 rpm and the centrifugal time is 10 minutes.
9. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 8, characterized in that: The freeze-drying temperature is -50°C and the drying time is 12 hours.
10. The method for preparing the pharmaceutical composition for treating alveolar echinococcosis according to claim 9, characterized in that: The tabletting pressure is 35KN.