CN111700875B - Method for improving bioavailability of acetylkitasamycin and pharmaceutical composition containing acetylkitasamycin - Google Patents
Method for improving bioavailability of acetylkitasamycin and pharmaceutical composition containing acetylkitasamycin Download PDFInfo
- Publication number
- CN111700875B CN111700875B CN202010590394.6A CN202010590394A CN111700875B CN 111700875 B CN111700875 B CN 111700875B CN 202010590394 A CN202010590394 A CN 202010590394A CN 111700875 B CN111700875 B CN 111700875B
- Authority
- CN
- China
- Prior art keywords
- acetylkitasamycin
- emulsion
- pharmaceutical composition
- parts
- mass concentration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/255—Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/78—Saururaceae (Lizard's-tail family)
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Emergency Medicine (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a method for improving bioavailability of acetylkitasamycin and a medicine composition containing the acetylkitasamycin. The invention also provides a pharmaceutical composition containing acetylkitasamycin, which is applied to the preparation of a pharmaceutical composition for treating respiratory tract infection diseases.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a method for improving bioavailability of acetylkitasamycin and a pharmaceutical composition containing acetylkitasamycin.
Background
Kitasamycin (Kitasamycin) is a group of 16-membered ring macrolide antibiotics mixture, and was prepared by fermentation and extraction from Streptomyces Kitasatoensis (Streptomyces Kitasatoensis) in 1953 at first. The action mechanism and the antibacterial spectrum of the antibacterial agent are similar to those of erythromycin, but the antibacterial agent has strong antibacterial effect on gram-positive bacteria and has effects on staphylococcus, hemolytic streptococcus, pneumococcus, diphtheria bacillus, tetanus bacillus, bacillus anthracis and the like. Acetylguitarycin (aceylleucomycin) is acetylated product of kitasamycin, and its main component is (3r, 4r, 5s, 6r, 8r, 9r, 10e, 12e, 15r) -3,9 acetoxyl-5- [0 (4-acyl-2, 6-dideoxy-3-C-methyl-alpha-l-ribose-hexopyranosyl) - (1-4) -2-0-acetyl 3, 6-dideoxy-3-dimethylamino-beta-d-glucopyranosyl ] -6-acetylaldehyde-4-methoxy-8, 15-dimethyl-10, 12-pentadecadien-15-lactone, and its characters are white or quasi-white powder, No odor and no bitter taste. The acetylkitasamycin is a drug-resistance-induced macrolide drug, and is mainly used for skin soft tissue infection, respiratory tract infection, streptococcus angina, scarlet fever, diphtheria, pertussis and the like caused by sensitive gram-positive bacteria, as well as gonorrhea, nongonococcal urethritis, acne and the like.
The acetylkitasamycin overcomes the bitter taste of other macrolide antibiotics, is convenient to take orally, and is particularly suitable for children to take. Acetylkitasamycin is very soluble in methanol, ethanol or acetone, insoluble in water or petroleum ether, and is a poorly soluble drug, and the powder of acetylkitasamycin is in a floating state in water, is not suitable for oral administration, and has low bioavailability.
Disclosure of Invention
To overcome the above-mentioned deficiencies of the prior art, it is a primary object of the present invention to provide a method for improving the bioavailability of acetylkitasamycin.
It is a second object of the present invention to provide a pharmaceutical composition comprising acetylkitasamycin.
The third purpose of the invention is to provide the application of the pharmaceutical composition containing acetylkitasamycin in preparing the medicines for treating respiratory tract infection.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for improving bioavailability of acetylkitasamycin comprising the steps of:
s1, dissolving acetylkitasamycin in a low-boiling-point organic solvent, and uniformly stirring to obtain a medicinal solution;
s2, dissolving hydroxypropyl-beta-cyclodextrin and soybean protein isolate in water, and stirring and uniformly mixing to obtain an emulsion;
s3, adding the solution obtained in the step S1 into the emulsion obtained in the step S2, stirring, carrying out high-pressure homogenization, removing the low-boiling organic solvent, and carrying out spray drying to obtain the powdery water-soluble acetylkitasamycin.
The soybean protein isolate is a common high-quality plant protein, is an amphiphilic polymer, and can be used for stabilizing an oil-water interface to prepare an oil-in-water emulsion system; the hydroxypropyl-beta-cyclodextrin is a water-soluble derivative of the beta-cyclodextrin, is a cyclic oligosaccharide with internal hydrophobicity and external hydrophilicity, can contain various hydrophobic substrates, is nontoxic, cheap and easy to obtain, and can obviously improve the physicochemical properties of medicaments; the invention selects hydroxypropyl-beta-cyclodextrin and soybean protein isolate as wall materials to prepare the acetyl kitasamycin microcapsules, and the hydroxypropyl-beta-cyclodextrin and the soybean protein isolate are utilized to carry out microencapsulation on the acetyl kitasamycin, so that the acetyl kitasamycin has good water solubility, thereby improving the bioavailability thereof.
Preferably, the low-boiling organic solvent is one or more of absolute ethyl alcohol, acetone or dichloromethane.
Preferably, the mass concentration of the acetylkitasamycin in the medicine solution is 5% -10%.
Preferably, the mass concentration of the hydroxypropyl-beta-cyclodextrin in the emulsion is 4% -9%, and the mass concentration of the soybean protein isolate in the emulsion is 10% -20%.
Preferably, the volume ratio of the medicinal solution to the emulsion is 1: 3-10.
Preferably, the pressure of the high-pressure homogenization treatment is 1000-2000bar, and the homogenization times are 1-3 times.
The invention also provides a pharmaceutical composition containing acetylkitasamycin, which comprises the acetylkitasamycin prepared by the method.
Preferably, the pharmaceutical composition containing acetylkitasamycin further comprises houttuynia cordata, astragalus membranaceus, notoginsenoside and allicin.
The herba Houttuyniae mainly contains decanoyl acetaldehyde, has inactivation effect on influenza virus type A3, respiratory syncytial virus and adenovirus, and has inhibitory effect on Staphylococcus aureus, hemolytic streptococcus, Bacillus proteus, diphtheria bacillus, enteritis bacillus, dysentery bacillus, Leptospira and fungi; the astragalus membranaceus mainly comprises polysaccharides, flavonoids, saponins and the like, has wide pharmacological action, obvious curative effect, safety and no toxicity, and has obvious functions of regulating humoral immunity and cellular immunity of an organism and enhancing the activity and the antiviral effect of natural killer cells; the panax notoginseng saponins comprise more than 20 saponin active substances such as ginsenoside Rb1, ginsenoside Rg1, notoginsenoside R1 and the like, 17 trace elements, proteins, abundant vitamins, polysaccharides and the like, and can promote the secretion of upper respiratory mucosa immune molecules and enhance the local immunity of the upper respiratory mucosa; the allicin is volatile oil obtained by distilling garlic, can be synthesized artificially, has broad-spectrum antibacterial and anti-inflammatory effects, has high bactericidal activity on various pathogenic bacteria, and also has the effects of resisting trichomonas, toxoplasma, fungi and cytomegalovirus infection, improving the immunity of the organism and the like; the invention can effectively enhance the pharmacological action of acetylkitasamycin after compounding the components with acetylkitasamycin and obviously improve the treatment effect of acetylkitasamycin on diseases such as respiratory tract infection and the like.
Preferably, the pharmaceutical composition containing acetylkitasamycin comprises the following components in parts by weight:
20-30 parts of acetylkitasamycin, 10-20 parts of houttuynia cordata, 7-12 parts of astragalus membranaceus, 5-10 parts of notoginsenoside and 5-10 parts of allicin.
After the acetylkitasamycin, the houttuynia cordata, the astragalus mongholicus, the notoginsenoside and the allicin are scientifically matched according to a certain proportion, the synergistic effect of each component can be better exerted, and therefore a better curative effect is obtained.
Preferably, in order to improve the application range of the medicament, the medicament composition containing acetylkitasamycin can be prepared into dosage forms of dripping pills, soft capsules, granules, tablets and the like.
The invention also provides application of the pharmaceutical composition containing acetylkitasamycin in preparing a medicine for treating respiratory tract infection diseases.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a method for improving bioavailability of acetylkitasamycin, which is characterized in that acetylkitasamycin is microencapsulated by utilizing hydroxypropyl-beta-cyclodextrin and soybean protein isolate to prepare a water-soluble acetylkitasamycin microcapsule product, so that the acetylkitasamycin has good water solubility, and the bioavailability can be effectively improved. Tests show that the water-soluble acetylkitasamycin microcapsule prepared by the invention not only has better encapsulation efficiency and drug-loading rate, but also has good release effect and obvious slow-release function; the acetylkitasamycin microcapsule product is applied to preparing the medicine for treating respiratory tract infection diseases to prepare the medicine composition containing the acetylkitasamycin, and the treatment test on a pneumonia model mouse shows that the composition has more obvious curative effect on treating the respiratory tract infection diseases compared with the medicine composition containing the conventional acetylkitasamycin.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The test methods used in the following experimental examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.
Research for improving bioavailability of acetylkitasamycin
Example 1A method for enhancing bioavailability of Acetylkitasamycin
The method comprises the following steps:
s1, dissolving 70g of acetylkitasamycin in absolute ethyl alcohol, and stirring at 3000r/min for 2min to obtain a medicine solution with the mass concentration of 7%;
s2, dissolving 60g of hydroxypropyl-beta-cyclodextrin and 140g of isolated soy protein in distilled water, and stirring at 3000r/min for 2min to obtain an emulsion, wherein the mass concentration of the hydroxypropyl-beta-cyclodextrin in the emulsion is 6%, and the mass concentration of the isolated soy protein in the emulsion is 14%;
s3, adding the medicinal solution obtained in the step S1 into the emulsion obtained in the step S2 according to the volume ratio of 1:6, stirring for 2min at 3000r/min, then placing under 1500bar pressure for high-pressure homogenization for 3 times, finally heating to remove absolute ethyl alcohol (no alcohol smell), and then carrying out spray drying to obtain a powdery water-soluble acetylkitasamycin microcapsule product.
Example 2A method for enhancing bioavailability of Acetylkitasamycin
The method comprises the following steps:
s1, dissolving 50g of acetylkitasamycin in absolute ethyl alcohol, and stirring at 2000r/min for 3min to obtain a medicine solution with the mass concentration of 5%;
s2, dissolving 40g of hydroxypropyl-beta-cyclodextrin and 100g of isolated soy protein in distilled water, and stirring at 2000r/min for 3min to obtain an emulsion, wherein the mass concentration of the hydroxypropyl-beta-cyclodextrin in the emulsion is 4%, and the mass concentration of the isolated soy protein in the emulsion is 10%;
s3, adding the medicinal solution obtained in the step S1 into the emulsion obtained in the step S2 according to the volume ratio of 1:3, stirring for 3min at 2000r/min, then placing under 1000bar pressure for high-pressure homogenization for 2 times, finally heating to remove absolute ethyl alcohol (no alcohol smell), and then carrying out spray drying to obtain a powdery water-soluble acetylkitasamycin microcapsule product.
Example 3A method for improving bioavailability of Acetylkitasamycin
The method comprises the following steps:
s1, dissolving 100g of acetylkitasamycin in absolute ethyl alcohol, and stirring for 1min at 4000r/min to obtain a medicine solution with the mass concentration of 10%;
s2, dissolving 90g of hydroxypropyl-beta-cyclodextrin and 200g of isolated soy protein in distilled water, and stirring for 1min at 4000r/min to obtain an emulsion, wherein the mass concentration of the hydroxypropyl-beta-cyclodextrin in the emulsion is 9%, and the mass concentration of the isolated soy protein in the emulsion is 20%;
s3, adding the medicinal solution obtained in the step S1 into the emulsion obtained in the step S2 according to the volume ratio of 1:10, stirring for 1min at 4000r/min, then placing under 2000bar pressure for high-pressure homogenization for 1 time, finally heating to remove absolute ethyl alcohol (no alcohol smell), and then carrying out spray drying to obtain a powdery water-soluble acetylkitasamycin microcapsule product.
Comparative example 1A method for improving bioavailability of Acetylkitasamycin
Comparative example 1 differs from example 1 in that: the mass concentration of the traditional Chinese medicine solution in the step S1 is 15%.
Comparative example 2 a method for improving bioavailability of acetylkitasamycin
Comparative example 2 differs from example 1 in that: the mass concentration of the soy protein isolate in the emulsion in step S2 was 7%. Comparative example 3 a method for improving bioavailability of acetylkitasamycin
Comparative example 3 differs from example 1 in that: the hydroxypropyl- β -cyclodextrin in step S2 was replaced with maltodextrin.
Experimental example 1 encapsulation efficiency and drug loading assay
(1) 90mg of acetylkitasamycin microcapsules are dissolved in quantitative water, the solution is quickly centrifuged at high speed, supernatant is taken to measure the absorbance value at 231nm, the concentration value is calculated according to a regression equation (refer to the research of the method for examining the dissolution rate of acetylkitasamycin particles), each group of samples is continuously subjected to experiments for 3 times, the average value is taken, and the encapsulation efficiency is obtained according to the following formula.
The encapsulation efficiency (1-acetylkitasamycin content on the surface of the capsule/total acetylkitasamycin content in the capsule) x 100%.
(2) Taking 90mg acetylkitasamycin microcapsules, placing the microcapsules in a 100mL volumetric flask, adding a proper amount of ethanol, fixing the volume to the scale with 0.01mol/L hydrochloric acid, ultrasonically treating for 10min to completely release the acetylkitasamycin, performing osmosis filtration with a 0.8-micron microporous filter membrane, taking filtrate, measuring the absorbance value of the filtrate at 231nm, continuously performing experiments for 3 times for each group of samples, taking an average value, calculating a concentration value according to a regression equation, and obtaining the drug loading rate according to the following formula.
The drug loading capacity/%, which is the content of acetylkitasamycin/the total mass of the capsule, is multiplied by 100%.
As shown in the results of Table 1, when acetyl kitasamycin is microencapsulated by hydroxypropyl-beta-cyclodextrin and isolated soy protein, the encapsulating rate is 90.54%, and the drug loading rate is 32.33%; the concentration of the liquid medicine of the acetylkitasamycin and the dosage of the soybean protein isolate influence the encapsulation efficiency and the drug loading of the product; in addition, the selection of proper wall materials has a great influence on the encapsulation efficiency and drug loading of the acetylkitasamycin.
TABLE 1 encapsulation efficiency and drug loading of acetylkitasamycin microcapsule products
| Group of | Encapsulation ratio% | Loading capacity/%) |
| Example 1 | 90.54 | 9.33 |
| Example 2 | 87.56 | 8.85 |
| Example 3 | 89.98 | 8.21 |
| Comparative example 1 | 72.47 | 5.32 |
| Comparative example 2 | 73.32 | 5.65 |
| Comparative example 3 | 74.66 | 5.15 |
Experimental example 2 simulated release experiment in gastric fluid environment
The acetylkitasamycin powder (90mg) of examples 1 to 3 was added to 50mL of simulated gastric fluid (0.01 mol/L HC1 solution containing 0.09mol/L NaC1, pH 2.0), and the mixture was put on an oscillator at 37 ℃ and oscillated at a rate of 50r/min, and the resultant mixture was sampled at predetermined times (1h, 3h, and 5h), and then the absorbance of acetylkitasamycin was measured at a wavelength of 231nm by UV spectrophotometry to calculate the drug concentration, and the release rate was determined according to the following formula.
Release rate/% ([ amount of acetylkitasamycin released in gastric juice simulant/(mass of added acetylkitasamycin powder x drug loading) ] × 100.
As shown in the results of Table 2, the acetylkitasamycin microcapsule product is easy to damage under the acidic condition of simulated gastric juice, so that the content is released, the cumulative release rate can reach 96.63% after the acetylkitasamycin microcapsule product is basically released in the simulated gastric juice environment after 5 hours, and the release rate of the comparative examples 1-3 is higher than that of the examples, which shows that the acetylkitasamycin microcapsule product has good release effect and good sustained and controlled release effect in the simulated gastric juice environment.
TABLE 2 Release of acetylkitasamycin microcapsules product in simulated gastric fluid environment
As can be seen from the comprehensive experimental examples 1-2, the water-soluble acetylkitasamycin microcapsule prepared by the invention not only has better encapsulation efficiency and drug-loading rate, but also has good release effect and obvious slow release function.
(II) study of pharmaceutical composition comprising acetylkitasamycin
Example 4A pharmaceutical composition comprising Acetylkitasamycin
Comprises the following components in parts by weight:
25kg of acetylkitasamycin prepared by the method of the embodiment 1, 15kg of houttuynia cordata, 10kg of astragalus membranaceus, 7.5kg of notoginsenoside and 7.5kg of allicin.
The preparation method of the composition comprises the following steps: mixing acetylkitasamycin, herba Houttuyniae, radix astragali, notoginsenoside and garlicin, pulverizing into superfine powder with particle size of 10-12 μm with superfine pulverizing equipment, and packaging.
Example 5A pharmaceutical composition comprising Acetylkitasamycin
Comprises the following components in parts by weight:
20kg of acetylkitasamycin prepared by the method of the embodiment 1, 10kg of houttuynia cordata, 7kg of astragalus membranaceus, 5kg of notoginsenoside and 5kg of allicin.
The preparation of the above composition is the same as in example 1.
Example 6A pharmaceutical composition comprising Acetylkitasamycin
Comprises the following components in parts by weight:
30kg of acetylkitasamycin prepared by the method of the embodiment 1, 20kg of houttuynia cordata, 12kg of astragalus membranaceus, 10kg of notoginsenoside and 10kg of allicin.
The preparation of the above composition is the same as in example 1.
Comparative example 4A pharmaceutical composition comprising Acetylkitasamycin
Compared with example 4, the amount of acetylkitasamycin was 15 kg.
Comparative example 5A pharmaceutical composition comprising Acetylkitasamycin
Compared with example 4, the amount of notoginsenoside is 5 kg.
Comparative example 6A pharmaceutical composition comprising Acetylkitasamycin
Compared with example 4, the notoginsenoside is replaced by conventional respiratory tract infection medicament, namely scutellaria baicalensis.
Comparative example 7A pharmaceutical composition comprising Acetylkitasamycin
In contrast to example 4, this comparative example used acetylkitasamycin which had not been water-soluble modified.
Experimental example 4 therapeutic efficacy of Acetylkitasamycin pharmaceutical composition of the present invention on pneumonia model mouse
(1) Animals: kunming mice, body weight (20 + -2 g), female and male half.
(2) Establishing a pneumonia model mouse: taking Kunming mice in batch, adaptively feeding for 1 week with concentration of 108cfu·mL-1The Salmonella typhimurium (Salmonella typhimurium) bacterial liquid is used for carrying out nasal drip infection on mice, and if the mice have symptoms of hair trembling, nodding breathing, accelerated breathing, abdominal breathing, asthma and the like, the mice are positive mice of a bacterial pneumonia model.
(3) Lung, spleen and thymus indices were determined and calculated: taking 10 normal mice as a normal control group; 80 bacterial pneumonia model mice were randomly divided into model group, examples 4-6 group and comparative examples 4-7 group, each group had 10 mice, and normal control group and model group were intraperitoneally injected with normal saline (0.5 mL. only-1) Examples 4-6 and comparative examples 4-7 were intraperitoneally injected with 600 mg-kg of the corresponding acetylkitasamycin-containing composition-1(0.5mL of the liquid medicine is prepared when in use), the medicine is taken 1 time for 1 day and is continuously taken for 7 days. 24h after the last dose, mice were sacrificed, spleen and thymus were weighed, and spleen and thymus indices were calculated.
Organ index/% (absolute weight of organ/animal body weight) × 100.
(4) Phagocytic function assay of alveolar macrophages: mice were sacrificed, the trachea was opened, cannulated, the lungs and bronchi were repeatedly washed through the trachea with 3mL (3 times, 1 mL/time) of cold physiological saline, bronchoalveolar lavage fluid was collected in a centrifuge tube, and then stained by reishi-giemsa staining method, i.e., l mL of alveolar lavage fluid was mixed with 0.5mL of 5% suspension of chicken red blood cells, the mixture was put on a clean glass slide, 0.3-0.5mL was added per slide, and then placed horizontally in a incubator and incubated at 30 ℃ for 30 min. Taking out, slowly washing with normal saline, air drying to obtain smear, counting the number of macrophage cells phagocytosing chicken erythrocyte in 100 alveolar macrophages under oil microscope, and calculating the phagocytosis percentage of alveolar macrophages.
As shown in the results in Table 3, compared with the normal control group, the spleen index and the thymus index of the mice in the model group are obviously increased, which indicates that the mice are infected by the Salmonella typhimurium to stimulate the body to form inflammation and promote the body immune organs to be enlarged, and the spleen index and the thymus index of the mice are obviously reduced and restored to the normal level after the pharmaceutical composition containing the acetylkitasamycin is injected, which indicates that the pharmaceutical composition containing the acetylkitasamycin can regulate the immune cells of the body to generate immune response, enhance the anti-inflammatory effect and have obvious curative effect on respiratory tract infection diseases. In addition, it can be seen that the bioavailability of the pharmaceutical composition prepared by using the water-soluble modified acetylkitasamycin is higher, and the influence on spleen and thymus index is more obvious.
TABLE 3 Effect of pharmaceutical compositions comprising Acetylkitasamycin on spleen and thymus index in groups of mice
The alveolar macrophage is an important component of natural immunity, and can directly phagocytize and digest various pathogens inside and outside cells, so that the number of pathogenic bacteria in a respiratory tract is reduced, the stimulation and damage effects of the pathogenic bacteria on a mucous membrane are reduced, and the respiratory tract inflammation is improved. As shown in the results in Table 4, the injection of the pharmaceutical composition containing acetylkitasamycin of the present invention can enhance the phagocytosis and killing effect of mouse macrophages on pathogenic bacteria (Salmonella typhimurium), reduce the number of pathogenic bacteria, thereby reducing respiratory tract injury and facilitating the recovery of infection. In addition, the water-soluble modified acetylkitasamycin prepared by the invention has higher bioavailability and can more obviously improve the phagocytic function of alveolar macrophages.
As can be seen from the above analysis, the acetylkitasamycin pharmaceutical composition is prepared by carrying out water-soluble modification on acetylkitasamycin by utilizing hydroxypropyl-beta-cyclodextrin and isolated soy protein, and has more obvious curative effect on treating respiratory tract infection diseases compared with the conventional acetylkitasamycin-containing pharmaceutical composition.
TABLE 4 Effect of pharmaceutical compositions comprising Acetylkitasamycin on macrophage phagocytosis
| Group of | Number of animals/animal | Percent phagocytosis/%) |
| Normal control group | 10 | 32.5±3.3 |
| Model set | 10 | 37.4±3.1 |
| Example 4 | 10 | 49.1±3.7 |
| Example 5 | 10 | 48.2±3.5 |
| Example 6 | 10 | 48.9±3.8 |
| Comparative example 4 | 10 | 40.1±3.5 |
| Comparative example 5 | 10 | 40.4±3.6 |
| Comparative example 6 | 10 | 41.6±3.4 |
| Comparative example 7 | 10 | 41.5±3.5 |
The above description has been made in detail with respect to the specific embodiments of the present invention, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in the embodiments without departing from the principles and spirit of the invention, and these embodiments are still within the scope of the invention.
Claims (5)
1. A method for improving bioavailability of acetylkitasamycin comprising the steps of:
s1, dissolving acetylkitasamycin in a low-boiling-point organic solvent, and uniformly stirring to obtain a medicinal solution; the mass concentration of the acetylkitasamycin in the medicinal solution is 5-10%;
s2, dissolving hydroxypropyl-beta-cyclodextrin and soybean protein isolate in water, and stirring and uniformly mixing to obtain an emulsion; the mass concentration of the hydroxypropyl-beta-cyclodextrin in the emulsion is 4% -9%, and the mass concentration of the soybean protein isolate in the emulsion is 10% -20%;
s3, adding the solution obtained in the step S1 into the emulsion obtained in the step S2, stirring, carrying out high-pressure homogenization, removing low-boiling organic solvent, and carrying out spray drying to obtain powdery water-soluble acetylkitasamycin;
the volume ratio of the medicinal solution to the emulsion is 1: 3-10; the low-boiling-point organic solvent is one or more of absolute ethyl alcohol, acetone or dichloromethane.
2. The method for improving the bioavailability of acetylkitasamycin as claimed in claim 1, wherein the pressure of the high-pressure homogenization treatment is 1000-2000bar, and the homogenization times are 1-3.
3. Acetylkitasamycin prepared by the process of claim 1.
4. A pharmaceutical composition comprising acetylkitasamycin as claimed in claim 3, characterised by consisting of the following ingredients in parts by weight: 20-30 parts of acetylkitasamycin, 10-20 parts of houttuynia cordata, 7-12 parts of astragalus membranaceus, 5-10 parts of notoginsenoside and 5-10 parts of allicin.
5. Use of the pharmaceutical composition comprising acetylkitasamycin of claim 4 in the manufacture of a medicament for the treatment of respiratory tract infectious diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010590394.6A CN111700875B (en) | 2020-06-24 | 2020-06-24 | Method for improving bioavailability of acetylkitasamycin and pharmaceutical composition containing acetylkitasamycin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010590394.6A CN111700875B (en) | 2020-06-24 | 2020-06-24 | Method for improving bioavailability of acetylkitasamycin and pharmaceutical composition containing acetylkitasamycin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111700875A CN111700875A (en) | 2020-09-25 |
| CN111700875B true CN111700875B (en) | 2022-06-14 |
Family
ID=72542693
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010590394.6A Active CN111700875B (en) | 2020-06-24 | 2020-06-24 | Method for improving bioavailability of acetylkitasamycin and pharmaceutical composition containing acetylkitasamycin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111700875B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101209244A (en) * | 2006-12-26 | 2008-07-02 | 重庆大新药业股份有限公司 | Method for producing acetylkitasamycin microcapsule type powder |
| CN105661545A (en) * | 2016-01-28 | 2016-06-15 | 武汉欧米嘉生物医药有限公司 | Alpha-linolenic acid microcapsule capable of being directly used for cooking and preparation method of alpha-linolenic acid microcapsule |
| CN107048405A (en) * | 2017-03-03 | 2017-08-18 | 武汉锶博睿医药技术有限公司 | Aliphatic acid component microcapsules and preparation method thereof |
| CN107823173A (en) * | 2017-11-24 | 2018-03-23 | 武汉人福药业有限责任公司 | A kind of acetylkitasamycin capsule and preparation method thereof |
-
2020
- 2020-06-24 CN CN202010590394.6A patent/CN111700875B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101209244A (en) * | 2006-12-26 | 2008-07-02 | 重庆大新药业股份有限公司 | Method for producing acetylkitasamycin microcapsule type powder |
| CN105661545A (en) * | 2016-01-28 | 2016-06-15 | 武汉欧米嘉生物医药有限公司 | Alpha-linolenic acid microcapsule capable of being directly used for cooking and preparation method of alpha-linolenic acid microcapsule |
| CN107048405A (en) * | 2017-03-03 | 2017-08-18 | 武汉锶博睿医药技术有限公司 | Aliphatic acid component microcapsules and preparation method thereof |
| CN107823173A (en) * | 2017-11-24 | 2018-03-23 | 武汉人福药业有限责任公司 | A kind of acetylkitasamycin capsule and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 冷榨芝麻油微胶囊化及其制品品质研究;王晓霞;《中国优秀硕士学位论文全文数据库》;20150515(第5期);第I-II和57-58页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111700875A (en) | 2020-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20140087010A1 (en) | Preparation method for extractive of jinxuan hemorrhoid washing powder botanicals | |
| CN111647091B (en) | Radix pseudostellariae active hexa-carbon aldehyde oligosaccharide and preparation method and application thereof | |
| CN112587595B (en) | Traditional Chinese medicine composition for clearing heat and relieving exterior syndrome and preparation method thereof | |
| CN100500176C (en) | Chinese medicine composition with functions of expelling surficial evils and clearing away heat and toxic materials and its preparing method and application | |
| EP1663258A2 (en) | Pharmaceutical compositions and therapeutic treatment with oligo-beta- (1,3) - glucans | |
| CN108113962B (en) | Method for reducing astringency of traditional Chinese medicine oral preparation containing polyphenol | |
| CN111700875B (en) | Method for improving bioavailability of acetylkitasamycin and pharmaceutical composition containing acetylkitasamycin | |
| CN1169839C (en) | Wolfberry polysaccharide and its prepn. and application | |
| WO2022143514A1 (en) | Oral preparation containing caffeic acid ester and breviscapine, and preparation method therefor | |
| CN112755104B (en) | Antiepileptic pharmaceutical composition and preparation method and application thereof | |
| CN101732301B (en) | Application of chlorogenic acid in preparing medicines for preventing and curing senile dementia | |
| CN101220063B (en) | Novel method for preparing catalpol, medicament composition containing the same and uses thereof | |
| CN107595870B (en) | Brain-strengthening and nerve-soothing pharmaceutical composition, pharmaceutical preparation, application and preparation method | |
| CN100427117C (en) | Chinese proprietary medicine | |
| CN113827570A (en) | Method for preparing traditional Chinese medicine pellet preparation based on drug carrier technology and application thereof | |
| CN113082085A (en) | Cistanche tubulosa extract and preparation method thereof | |
| CN107260810A (en) | The Preparation method and use of high-purity clove leaf total iridoid glycoside extract and its preparation | |
| CN107753567B (en) | Anti-fatigue pharmaceutical composition and preparation method and application thereof | |
| CN103919845A (en) | Pharmaceutical composition for improving anoxia endurance and preparation method and application thereof | |
| CN102429946B (en) | Chinese medicinal composition for preparing anti-influenza virus medicament | |
| CN107865895A (en) | A kind of application of maidenhair extractive of general flavone in medicament for immunity enhancement is prepared | |
| CN117919352B (en) | Pharmaceutical composition for improving immunity of children | |
| CN107638522B (en) | Traditional Chinese medicine composition for mainly treating wind-cold type common cold and relieving exterior syndrome and clearing heat as well as preparation process and application thereof | |
| CN101390921A (en) | Composition of starwort total glycopeptides and total flavone and preparation method and uses thereof | |
| CN1366948A (en) | Nano Fufang Fufangteng preparation medicine and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221111 Address after: No.6 Dongbo Road, East District, Guangzhou Economic and Technological Development Zone, Guangdong 510000 Patentee after: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. Patentee after: GUANGDONG ZERUI PHARMACEUTICAL Co.,Ltd. Patentee after: Guangzhou Lianrui Pharmaceutical Co.,Ltd. Patentee after: Guangzhou Runlin Pharmaceutical Technology Co.,Ltd. Patentee after: Euphorbia Biological Medicine Co.,Ltd. Address before: No.6 Dongbo Road, East District, Guangzhou Economic and Technological Development Zone, Guangdong 510000 Patentee before: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right |