CN117695223A - Oligosaccharide atomizing agent based on guluronic acid oligosaccharide and preparation method thereof - Google Patents
Oligosaccharide atomizing agent based on guluronic acid oligosaccharide and preparation method thereof Download PDFInfo
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- CN117695223A CN117695223A CN202311662324.7A CN202311662324A CN117695223A CN 117695223 A CN117695223 A CN 117695223A CN 202311662324 A CN202311662324 A CN 202311662324A CN 117695223 A CN117695223 A CN 117695223A
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- Prior art keywords
- oligosaccharide
- guluronic acid
- oligosaccharides
- sodium alginate
- sodium chloride
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- 229920001542 oligosaccharide Polymers 0.000 title claims abstract description 711
- -1 guluronic acid oligosaccharide Chemical class 0.000 title claims abstract description 444
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 262
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 163
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Abstract
The invention provides an oligosaccharide atomizing agent based on guluronic acid oligosaccharide and a preparation method thereof, wherein the oligosaccharide atomizing agent comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The formula atomizing agent has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, and can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane, further enhance the antibiotic sterilization efficacy and prevent the formation of drug-resistant bacteria. In addition, a temporary protective film can be formed at the damaged part of the respiratory tract mucous membrane, lubrication is kept, secondary infection and physical injury are prevented, the treatment effect of the respiratory tract diseases is improved, and the course of the diseases is shortened. It also has effects in activating cells, removing heavy metals, resisting pulmonary fibrosis and free radical oxidation, and promoting recovery and activation of pulmonary function after healing. The preparation method has the advantages of simple process, easily available equipment, low cost and environment-friendly production process.
Description
Technical Field
The application relates to the technical field of biological medicine, in particular to an oligosaccharide atomizing agent based on guluronic acid oligosaccharide and a preparation method thereof.
Background
In many chronic respiratory diseases, the production of highly viscous/elastic mucus impedes clearance and prolongs infection and airway inflammation, and this "mucus barrier" exacerbates the difficulty of targeting therapy to the epithelial lung surface by the presence of bacterial biofilm on the epithelial surface, and the inability of sputum to drain in time can further lead to respiratory infections, dyspnea, spread of infection, and ultimately prolonged disease in the patient. The lung is the most frequent organ of human body connected with the outside through mouth and nose, so that the lung is the internal organ which is most easy to contact with various pathogenic microorganisms outside to infect germs, viruses and the like, and therefore, the anti-lung infection medicine and the protection medicine for increasing lung mucous membrane are important in preventing infectious diseases. The traditional medicines for treating lung infection are mostly antibiotics medicines for oral administration or injection, the receptor area is large, and unnecessary damage is easily caused to other normal tissues or organs. The aerosol inhalation treatment is more and more important because the dosage of the medicament is less than the dosage of oral administration or injection, and the medicament can directly act on the lesion part, and the medicament is only used locally in human body, and does not cause or causes little harm to other normal tissues or organs. The existing special atomizing agent for atomization treatment is very few, most of the atomizing agent is used by adopting a vein preparation to replace an atomization inhalation preparation, and because the vein preparation often contains preservatives such as phenol, nitrite and the like, asthma attacks can be induced after inhalation, and medicines of the non-atomization inhalation preparation cannot reach the effective atomizing particle requirements, cannot be cleared through respiratory tracts and can be deposited in lungs, so that the occurrence rate of lung infection is easily increased, the traditional atomization agent (dexamethasone, gentamicin and alpha-chymotrypsin) is widely applied in clinic, but the dosage, the treatment course and the treatment effect are not unified and standard, and the atomization agent is directly diluted by physiological saline, so that the concentration of the agent is uncontrollable, salty and astringent peculiar smell can be easily generated, part of patients have discomfort, psychological discomfort is further caused, and even some patients are not matched. If the aerosol inhalation treatment is irregular, the treatment effect can be directly affected, potential safety hazards are more likely to be brought, and the life and health of the patient are endangered. The current few special atomizing agents are also of health care type, and the special atomizing agents are not obvious in the aspects of inhibiting respiratory tract pathogenic microorganisms and viruses, expelling phlegm and reducing respiratory tract secretion in the treatment of respiratory tract infection, have poor effects and have unobvious anti-inflammation effects.
Disclosure of Invention
Based on the above problems, an oligosaccharide nebulizer based on guluronic acid oligosaccharides is provided, which can be used for treating respiratory tract infections, especially lung infections and diluted sputum, and at the same time can activate the immune system and promote immune system repair.
In addition, the application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide, which has simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The guluronic acid oligosaccharide in the components has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of the sputum by changing the assembly mode of macromolecular substances in the mucus, and can generate a plurality of small holes penetrating the inside and the outside of the sputum, so that the elasticity, the viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently discharged smoothly. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of influenza A (H1N 1) through respiratory tract, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the side effects are not promoted on the recovery of respiratory tract functions, the guluronic acid oligosaccharide in the composition can also reduce the pain of the patients through enhancing humoral immunity and cellular immunity and directly or indirectly inhibiting the replication of viruses such as influenza A (H1N 1), and the mechanism of the guluronic acid oligosaccharide in the composition can effectively avoid the formation of antibacterial bacteria through promoting the aggregation of pathogenic bacteria and the disintegration of biological films and can also omnidirectionally inhibit inflammatory reaction besides the direct antibacterial effect, and the mechanism is mainly as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharides described in the components of the present application exert a mild and non-irritating effect, which is very beneficial for the treatment of respiratory diseases including chronic obstructive pulmonary disease.
Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.05% -0.8%; the sodium alginate comprises the following components: 0.02% -0.5%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizer based on guluronic acid oligosaccharides further comprises chitosan; the components of the paint comprise the following components in percentage by weight: the guluronic acid oligosaccharide: 0.08% -0.5%; the sodium alginate comprises the following components: 0.05% -0.8%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizer based on guluronic acid oligosaccharides further comprises chitosan; the components of the paint comprise the following components in percentage by weight: the guluronic acid oligosaccharide: 0.02% -0.1%; the sodium alginate comprises the following components: 0.01% -0.025%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizer based on guluronic acid oligosaccharides further comprises chitosan; the components of the paint comprise the following components in percentage by weight: the guluronic acid oligosaccharide: 1.0% -2.5%; the sodium alginate comprises the following components: 1.0% -1.5%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened.
Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful.
In addition, the sodium alginate of the atomization agent can form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the acting time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like).
In one embodiment, the guluronic acid oligosaccharide is a linear polysaccharide of alpha-1, 4-L guluronic acid and beta-1, 4-D-mannuronic acid linked by a 1.fwdarw.4 glycosidic bond; the sodium alginate is formed by connecting beta-D-mannuronic acid and alpha-L-guluronic acid according to a (1-4) bond.
The oligosaccharide atomizing agent based on the guluronic acid oligosaccharide provided by the invention has high deposition rate in the lung, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the antibiotic sterilization efficacy in respiratory diseases, wherein the guluronic acid oligosaccharide can damage the structure and the integrity of the sputum by changing the assembly mode of macromolecular substances in mucus, can generate a plurality of small holes penetrating the inside and outside of the sputum, greatly reduce the elasticity, the viscosity and the like of the sputum, and further thin, break and facilitate smooth discharge of the sputum of a patient. In addition, the application can also enhance humoral immunity and cellular immunity, directly or indirectly inhibit the replication of viruses such as influenza A (H1N 1) and the like, and promote cell death by promoting aggregation of pathogenic bacteria and disruption of biological membranes, can effectively avoid the formation of drug-resistant bacteria, can also omnidirectionally inhibit the effect of inflammatory reaction besides the direct antibacterial effect, and can relieve the pain of patients. Furthermore, the guluronic acid oligosaccharides described in the components of the present application exert a mild and non-irritating effect, which is very beneficial for the treatment of respiratory diseases including chronic obstructive pulmonary disease. The sodium alginate is natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, is mainly used as a stabilizer and a film forming agent, forms a thin film together with phagocytes at the damaged part of the respiratory tract, can form a protective film at the serious part of the infection in the treatment process of the respiratory tract infection, plays a role in temporarily protecting the damaged part of the mucous membrane, ensures that the damaged part of the infection is not easy to be secondarily infected, improves the treatment effect and shortens the course of the disease, has the effects of moisturizing and moisturizing, has the effects of resisting free radical oxidation, inhibiting bacteria, diminishing inflammation, resisting viruses and resisting coagulation, can keep the damaged part of the mucous membrane lubricated, prevents phlegm invasion, and can promote wound healing while providing a warm and moist environment for the formation of new mucous membrane. In addition, the atomization preparation can better excite functions through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist virus, resist free radical oxidation, activate cells and remove heavy metals, so that the atomization preparation not only can well treat respiratory tract infection diseases of patients, but also is helpful for recovery after recovery of pulmonary diseases of the patients, activating pulmonary functions, and is very helpful for cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps S11-S13:
s11, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S12, adding the guluronic acid oligosaccharide with the given weight into the sodium alginate-sodium chloride solution obtained in the step S11, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide is a component which is very soluble in water, the guluronic acid oligosaccharide with a given weight is added into a sufficient amount of sodium alginate-sodium chloride solution, the solution is rapidly dissolved, insoluble impurities are separated, and a purer mixed solution can be obtained through filtration, so that the impurities can be removed for an atomized preparation.
And S13, keeping the temperature of the mixed filtrate in the step S12 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S11 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S11 with sodium bicarbonate.
In one embodiment, step S11 heats the distilled/purified water to a temperature between 80℃and 90 ℃.
In one embodiment, the preparation method further comprises a step S14 of standing the atomizing agent obtained in the step S13 in an alternating magnetic field for 0.5-1.5 hours.
In one embodiment, the preparation method further comprises a step S15 of filling the atomizing agent obtained in the step S14 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S13 to step S14.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S13 with acetic acid.
In one embodiment, the preparation method further comprises a step S12 of adding the predetermined weight of the guluronic acid oligosaccharide into a sufficient amount of distilled water/purified water, stirring, filtering to obtain a guluronic acid oligosaccharide solution, and then adding the obtained guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S11 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
The application also provides another oligosaccharide atomizing agent based on guluronic acid oligosaccharide, which has good treatment effect on edema caused by inflammation and also has promotion effect on enhancing the radiation resistance of organisms besides the effects.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The guluronic acid oligosaccharide in the components has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of the sputum by changing the assembly mode of macromolecular substances in the mucus, and can generate a plurality of small holes penetrating the inside and the outside of the sputum, so that the elasticity, the viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently discharged smoothly. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of influenza A (H1N 1) through respiratory tract, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the side effects are not promoted on the recovery of respiratory tract functions, the guluronic acid oligosaccharide in the composition can also reduce the pain of the patients through enhancing humoral immunity and cellular immunity and directly or indirectly inhibiting the replication of viruses such as influenza A (H1N 1), and the mechanism of the guluronic acid oligosaccharide in the composition can effectively avoid the formation of antibacterial bacteria through promoting the aggregation of pathogenic bacteria and the disintegration of biological films and can also omnidirectionally inhibit inflammatory reaction besides the direct antibacterial effect, and the mechanism is mainly as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharides described in the components of the present application exert a mild and non-irritating effect, which is very beneficial for the treatment of respiratory diseases including chronic obstructive pulmonary disease. Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum. In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.002% -0.005%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.05% -0.8%; the sodium alginate comprises the following components: 0.02% -0.5%; the carrageenan oligosaccharides: 0.0025% -0.01%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.08% -0.5%; the sodium alginate comprises the following components: 0.05% -0.8%; the carrageenan oligosaccharides: 0.005% -0.008%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.02% -0.1%; the sodium alginate comprises the following components: 0.01% -0.025%; the carrageenan oligosaccharides: 0.0015% -0.004%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the guluronic acid oligosaccharide is a linear polysaccharide of alpha-1, 4-L guluronic acid and beta-1, 4-D-mannuronic acid linked by a 1.fwdarw.4 glycosidic bond; the sodium alginate is formed by connecting beta-D-mannuronic acid and alpha-L-guluronic acid according to a (1-4) bond.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened. Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful. Besides, the sodium alginate of the atomization agent can also form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the action time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like). In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps of S21-S23:
s21, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S22, adding carrageenan oligosaccharide and guluronic acid oligosaccharide with given weights into the sodium alginate-sodium chloride solution obtained in the step S21, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide and the carrageenan oligosaccharide are all water-soluble components, the predetermined weight of the carrageenan oligosaccharide and the guluronic acid oligosaccharide are added into a sufficient amount of sodium alginate-sodium chloride solution, the solution is rapidly dissolved, insoluble impurities are separated, and a purer mixed solution can be obtained through filtration, so that the impurities can be removed for an atomized preparation.
And S23, keeping the temperature of the mixed filtrate in the step S22 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S21 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S21 with sodium bicarbonate.
In one embodiment, step S21 heats the distilled/purified water to a temperature between 80 ℃ and 90 ℃.
In one embodiment, the preparation method further comprises a step S24 of standing the atomizing agent obtained in the step S23 in an alternating magnetic field for 0.5-1.5 hours.
In one embodiment, the preparation method further comprises a step S25 of filling the atomizing agent obtained in the step S24 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S23 and step S24.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S23 with acetic acid.
In one embodiment, the preparation method further includes a step S22 of adding predetermined weight of carrageenan oligosaccharide and guluronic acid oligosaccharide into sufficient distilled water/purified water, stirring, filtering to obtain a carrageenan oligosaccharide-guluronic acid oligosaccharide solution, and adding the obtained carrageenan oligosaccharide-guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S21 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
According to the above, the present application also provides an oligosaccharide atomizer based on guluronic acid oligosaccharide doped with a larger dose of carrageenan oligosaccharide to cope with severe edema or severe abnormal hyperplasia, but the administration period needs to be controlled, and the administration period is generally controlled to be no more than 2 weeks continuously, and the daily administration dose is no more than 25ml.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.5% -5.0%; the sodium alginate comprises the following components: 0.5% -5.0%; the carrageenan oligosaccharides: 0.01% -0.5%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.5% -5.0%; the sodium alginate comprises the following components: 0.5% -5.0%; the carrageenan oligosaccharides: 0.025% -0.125%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 1.0% -2.5%; the sodium alginate comprises the following components: 1.0% -1.5%; the carrageenan oligosaccharides: 0.025% -0.125%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.8% -2.0%; the sodium alginate comprises the following components: 0.6% -1.2%; the carrageenan oligosaccharides: 0.05% -0.15%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.8% -2.0%; the sodium alginate comprises the following components: 0.6% -1.2%; the carrageenan oligosaccharides: 0.1% -0.25%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
The present application also provides another oligosaccharide atomizer based on guluronic acid oligosaccharides.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The guluronic acid oligosaccharide in the components has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of the sputum by changing the assembly mode of macromolecular substances in the mucus, and can generate a plurality of small holes penetrating the inside and the outside of the sputum, so that the elasticity, the viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently discharged smoothly. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of influenza A (H1N 1) through respiratory tract, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the side effects are not promoted on the recovery of respiratory tract functions, the guluronic acid oligosaccharide in the composition can also reduce the pain of the patients through enhancing humoral immunity and cellular immunity and directly or indirectly inhibiting the replication of viruses such as influenza A (H1N 1), and the mechanism of the guluronic acid oligosaccharide in the composition can effectively avoid the formation of antibacterial bacteria through promoting the aggregation of pathogenic bacteria and the disintegration of biological films and can also omnidirectionally inhibit inflammatory reaction besides the direct antibacterial effect, and the mechanism is mainly as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharides described in the components of the present application exert a mild and non-irritating effect, which is very beneficial for the treatment of respiratory diseases including chronic obstructive pulmonary disease. Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum. In addition, the agar oligosaccharides as the effective components of the atomization preparation have the functions of moisture absorption and moisture retention, also have the functions of anti-inflammation, antioxidation and in-vivo free radical removal, are mainly used for protecting and diminishing inflammation of damaged parts of surface mucous membranes after being infected with the human respiratory tract together with sodium alginate, have the moisturizing function, can keep the damaged parts of the mucous membranes lubricated, prevent phlegm invasion and provide a warm and moist environment for the formation of new mucous membranes. The atomization agent also has an inhibiting effect on the development of tumors after atomization inhalation, can inhibit the growth of tumor tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.05% -0.8%; the sodium alginate comprises the following components: 0.02% -0.5%; the agar oligosaccharides: 0.03% -0.1%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.08% -0.5%; the sodium alginate comprises the following components: 0.05% -0.8%; the agar oligosaccharides: 0.05% -0.08%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 1.0% -2.5%; the sodium alginate comprises the following components: 0.8% -2.0%; the agar oligosaccharides: 0.15% -0.25%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 1.0% -2.5%; the sodium alginate comprises the following components: 0.8% -2.0%; the agar oligosaccharides: 0.2% -0.4%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 1.5% -2.0%; the sodium alginate comprises the following components: 1.0% -1.8%; the agar oligosaccharides: 0.12-0.18%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 1.8% -2.4%; the sodium alginate comprises the following components: 1.2% -1.8%; the agar oligosaccharides: 0.3% -0.35%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened. Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful. Besides, the sodium alginate of the atomization agent can also form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the action time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like). In addition, the agar oligosaccharides as the effective components of the atomization preparation have the functions of moisture absorption and moisture retention, also have the functions of anti-inflammation, antioxidation and in-vivo free radical removal, are mainly used for protecting and diminishing inflammation of damaged parts of surface mucous membranes after being infected with the human respiratory tract together with sodium alginate, have the moisturizing function, can keep the damaged parts of the mucous membranes lubricated, prevent phlegm invasion and provide a warm and moist environment for the formation of new mucous membranes. The atomization agent also has an inhibiting effect on the development of tumors after atomization inhalation, can inhibit the growth of tumor tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps S31-S33:
s31, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S32, adding the agar oligosaccharide and the guluronic acid oligosaccharide with the given weights into the sodium alginate-sodium chloride solution obtained in the step S31, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide is a component which is easy to dissolve in water, the guluronic acid oligosaccharide with a given weight is added into a sufficient amount of sodium alginate-sodium chloride solution, the solution is quickly dissolved, insoluble impurities are separated, the agar is used as marine polysaccharide, the viscosity is high, the water solubility is low, the agar is not easy to absorb, but the degraded agar oligosaccharide has good water solubility and is favorable for human absorption, the agar oligosaccharide with a given weight is added into the sufficient amount of sodium alginate-sodium chloride solution, and a purer mixed solution can be obtained through filtration, so that the impurities can be removed for an atomized preparation.
And S33, keeping the temperature of the mixed filtrate in the step S32 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S31 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S31 with sodium bicarbonate.
In one embodiment, step S31 heats the distilled/purified water to a temperature between 80℃and 90 ℃.
In one embodiment, the preparation method further comprises a step S34 of standing the atomizing agent obtained in the step S33 in an alternating magnetic field for 0.5-1.5 hours.
In one embodiment, the preparation method further comprises a step S35 of filling the atomizing agent obtained in the step S34 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S33 to step S34.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S33 with acetic acid.
In one embodiment, the preparation method further includes a step S32 of adding the predetermined weight of the agaragar oligosaccharide and the guluronic acid oligosaccharide into a sufficient amount of distilled water/purified water, stirring, filtering to obtain an agaragar oligosaccharide-guluronic acid oligosaccharide solution, and adding the obtained agaragar oligosaccharide-guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S31 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
According to the above, the present application also provides an oligosaccharide atomization agent based on guluronic acid oligosaccharide, which has good therapeutic effect on edema caused by inflammation, and also has promotion effect on enhancing the radiation resistance and anti-tumor of the organism.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The guluronic acid oligosaccharide in the components has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of the sputum by changing the assembly mode of macromolecular substances in the mucus, and can generate a plurality of small holes penetrating the inside and the outside of the sputum, so that the elasticity, the viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently discharged smoothly. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of influenza A (H1N 1) through respiratory tract, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the side effects are not promoted on the recovery of respiratory tract functions, the guluronic acid oligosaccharide in the composition can also reduce the pain of the patients through enhancing humoral immunity and cellular immunity and directly or indirectly inhibiting the replication of viruses such as influenza A (H1N 1), and the mechanism of the guluronic acid oligosaccharide in the composition can effectively avoid the formation of antibacterial bacteria through promoting the aggregation of pathogenic bacteria and the disintegration of biological films and can also omnidirectionally inhibit inflammatory reaction besides the direct antibacterial effect, and the mechanism is mainly as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharides described in the components of the present application exert a mild and non-irritating effect, which is very beneficial for the treatment of respiratory diseases including chronic obstructive pulmonary disease. Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum. In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Meanwhile, the compound preparation also has an inhibiting effect on the development of tumors, can inhibit the growth of tumor cells and tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.05% -0.8%; the sodium alginate comprises the following components: 0.02% -0.5%; the carrageenan oligosaccharides: 0.0015% -0.005%; the agar oligosaccharides: 0.015% -0.05%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.08% -0.5%; the sodium alginate comprises the following components: 0.05% -0.8%; the carrageenan oligosaccharides: 0.0025% -0.004%; the agar oligosaccharides: 0.025% -0.04%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.002% -0.005%; the agar oligosaccharides: 0.018% -0.025%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.05% -0.8%; the sodium alginate comprises the following components: 0.02% -0.5%; the carrageenan oligosaccharides: 0.0025% -0.01%; the agar oligosaccharides: 0.012% -0.024%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.25% -0.35%; the sodium alginate comprises the following components: 0.015% -0.3%; the carrageenan oligosaccharides: 0.003% -0.0045%; the agar oligosaccharides: 0.015% -0.05%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened. Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful. Besides, the sodium alginate of the atomization agent can also form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the action time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like). In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Meanwhile, the compound preparation also has an inhibiting effect on the development of tumors, can inhibit the growth of tumor cells and tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps S41-S43:
s41, adding sodium alginate and sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S42, adding carrageenan oligosaccharide, agar oligosaccharide and guluronic acid oligosaccharide with given weights into the sodium alginate-sodium chloride solution obtained in the step S41, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide and the carrageenan oligosaccharide are water-soluble components, the predetermined weight of the guluronic acid oligosaccharide and the carrageenan oligosaccharide are added into a sufficient amount of sodium alginate-sodium chloride solution, the guluronic acid oligosaccharide and the carrageenan oligosaccharide are rapidly dissolved, insoluble impurities are separated, the agar is used as a marine polysaccharide, the viscosity is high, the water solubility is low, the agar is not easily absorbed, but the degraded agar oligosaccharide has good water solubility and is favorable for human absorption, the predetermined weight of the agar oligosaccharide is added into a sufficient amount of sodium alginate-sodium chloride solution, the rapid dissolution is also achieved, the insoluble impurities are also separated, and thus, a purer mixed solution can be obtained through filtration, and the impurities can be removed for an atomized preparation.
And S43, keeping the temperature of the mixed filtrate in the step S42 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S41 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S41 with sodium bicarbonate.
In one embodiment, step S41 heats the distilled/purified water to a temperature between 80℃and 90 ℃.
In one embodiment, the preparation method further comprises a step S44 of standing the atomizing agent obtained in the step S43 in an alternating magnetic field for 0.5 to 1.5 hours.
In one embodiment, the preparation method further comprises a step S45 of filling the atomizing agent obtained in the step S44 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S43 to step S44.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S43 with acetic acid.
In one embodiment, the preparation method further includes a step S42 of adding predetermined weight of carrageenan oligosaccharide, agar oligosaccharide and guluronic acid oligosaccharide into sufficient distilled water/purified water, stirring, filtering to obtain an agar oligosaccharide-carrageenan oligosaccharide-guluronic acid oligosaccharide solution, and adding the obtained agar oligosaccharide-carrageenan oligosaccharide-guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S41 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
According to the above, the present application also provides an oligosaccharide atomizer based on guluronic acid oligosaccharide doped with a larger dose of carrageenan oligosaccharide to cope with severe edema or severe abnormal hyperplasia, but the administration period needs to be controlled, and the administration period is generally controlled to be no more than 2 weeks continuously, and the daily administration dose is no more than 25ml.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.5% -5.0%; the sodium alginate comprises the following components: 0.5% -5.0%; agar oligosaccharides: 0.01% -0.5%; the carrageenan oligosaccharides: 0.01% -0.5%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.5% -5.0%; the sodium alginate comprises the following components: 0.5% -5.0%; agar oligosaccharides: 0.1% -0.25%; the carrageenan oligosaccharides: 0.025% -0.125%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 1.0% -2.5%; the sodium alginate comprises the following components: 1.0% -1.5%; agar oligosaccharides: 0.025% -0.15%; the carrageenan oligosaccharides: 0.025% -0.125%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.8% -2.0%; the sodium alginate comprises the following components: 0.6% -1.2%; agar oligosaccharides: 0.035% -0.08%; the carrageenan oligosaccharides: 0.05% -0.15%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: the guluronic acid oligosaccharide: 0.8% -2.0%; the sodium alginate comprises the following components: 0.6% -1.2%; agar oligosaccharides: 0.15% -0.35%; the carrageenan oligosaccharides: 0.1% -0.25%; the sodium chloride: 0.1% -0.9%; the distilled/purified water: the balance.
In accordance with the foregoing, the present application also provides another oligosaccharide atomizer based on guluronic acid oligosaccharides. An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance. Under the effect of the diastole, the product has the functions of dilating bronchi, relieving bronchus smooth muscle and relieving airflow limitation, and can well prevent the air pipe of partial people from spasm under the stimulation of drugs, thereby achieving the purposes of spasmolysis and asthma relieving, enabling the atomization agent to be deposited deeper and improving the treatment efficacy.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance.
In the embodiment, under the action of the diastole agent, the atomization agent has the functions of expanding bronchi, relieving bronchus smooth muscles and relieving airflow limitation, and can well prevent the air pipes of partial people from spasm under the stimulation of medicaments, thereby achieving the purposes of spasmolysis and asthma relieving, enabling the atomization agent to be deposited deeper and improving the treatment efficacy.
In accordance with the foregoing, the present application also provides another oligosaccharide atomizer based on guluronic acid oligosaccharides. An oligosaccharide atomizer based on guluronic acid oligosaccharide, and also comprises antibacterial agent; the components of the paint comprise the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; sodium chloride: 0.1% -0.9%; the bacteriostat comprises the following components: 0.01% -0.03%; distilled/purified water: the balance. In this embodiment, the bacteriostatic agent may be an antibiotic drug. Because the pure antibiotics generally need to be metabolized by the liver to act, the antibiotics have low fat solubility and high water solubility, are less combined with the mucous membrane tissues of the lung airway, have low deposition rate in the lung, have low affinity with glucocorticoid receptor, have short residence time in the airway, are difficult to exert local anti-inflammatory effect by aerosol inhalation, and have poor curative effect. The guluronic acid oligosaccharide has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum in respiratory diseases, and can be completely carried and deposited at focus positions after being atomized by adding the antibacterial agent with the predetermined amount in the scheme, thereby achieving better treatment effect.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; sodium chloride: 0.1% -0.9%; the bacteriostat comprises the following components: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; the bacteriostat comprises the following components: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; the bacteriostat comprises the following components: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; bacteriostat: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the diastolic agent is at least one of albuterol, terbutaline, ipratropium bromide.
In one embodiment, the antibacterial agent is at least one of gentamicin, amikacin, vancomycin.
In one embodiment, the salbutamol is an inhalation salbutamol sulphate solution.
In one embodiment, the terbutaline is terbutaline sulfate nebulized solution.
In one embodiment, the ipratropium bromide is ipratropium bromide aerosol inhalation solution.
In one embodiment, the gentamicin adopts gentamicin injection, gentamicin tablet or directly adopts gentamicin liquid, and is cheap and easy to obtain.
In one embodiment, the amikacin is a crystalline powder of amikacin or an aqueous amikacin solution dissolved in distilled water in a specific ratio.
In one embodiment, the vancomycin is vancomycin powder or a solution obtained by adding the vancomycin powder into water for injection.
In one embodiment, the antimicrobial agent comprises a dialkyl quaternary ammonium salt and chlorhexidine acetate in equal weight percentages.
The oligosaccharide atomizing agent based on the guluronic acid oligosaccharide provided by the invention has the advantages that the pure antibacterial agent generally needs to be metabolized by the liver to act, the fat solubility is low, the water solubility is high, the combination with the lung airway mucosa tissue is less, the deposition rate in the lung is low, the affinity with glucocorticoid receptor is low, the residence time in the airway is short, the local anti-inflammatory effect is difficult to be exerted through atomization inhalation, and the curative effect is poor. The guluronic acid oligosaccharide has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum in respiratory diseases, and can be completely carried and deposited at focus positions together after being atomized by adding the antibacterial agent with the predetermined amount in the scheme, thereby playing a role in synergy.
Detailed Description
In order to make the above objects, features and advantages of the present application more comprehensible, embodiments accompanied with the present application are described in detail below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. This application is, however, susceptible of embodiment in many other forms than those described herein and similar modifications can be made by those skilled in the art without departing from the spirit of the application, and therefore the application is not to be limited to the specific embodiments disclosed below.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the description of the application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The components have high intrapulmonary deposition rate of guluronic acid oligosaccharide, have multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, and can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of sputum by changing the assembly mode of macromolecular substances in mucus, and can generate a plurality of small holes penetrating the inside and outside of the sputum, so that the elasticity, viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently and smoothly discharged. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of the influenza A (H1N 1) through respiratory tracts, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the treatment does not promote the recovery of the respiratory tract functions, the guluronic acid oligosaccharide in the composition can enhance humoral immunity and cellular immunity, directly or indirectly inhibit the replication of the viruses such as the influenza A (H1N 1) and the like, the pain of the patients can be relieved, and the guluronic acid oligosaccharide in the composition can effectively avoid the formation of drug resistant bacteria by promoting the aggregation and disintegration of biological membranes and accelerate the death of cells, and besides the direct antibacterial effect, the mechanism of the drug resistant oligosaccharide can also inhibit inflammatory reaction in an all-around manner, and the mechanism is as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharide in the components of the application plays a role in mild and non-irritating role, which is very beneficial to the treatment of respiratory diseases including chronic obstructive pneumonia and the like.
Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.05% -0.8%; sodium alginate: 0.02% -0.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizer based on guluronic acid oligosaccharides further comprises chitosan; the components of the paint comprise the following components in percentage by weight: guluronic acid oligosaccharides: 0.08% -0.5%; sodium alginate: 0.05% -0.8%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizer based on guluronic acid oligosaccharides further comprises chitosan; the components of the paint comprise the following components in percentage by weight: guluronic acid oligosaccharides: 0.02% -0.1%; sodium alginate: 0.01% -0.025%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizer based on guluronic acid oligosaccharides further comprises chitosan; the components of the paint comprise the following components in percentage by weight: guluronic acid oligosaccharides: 1.0% -2.5%; sodium alginate: 1.0% -1.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened.
Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful.
In addition, the sodium alginate of the atomization agent can form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the acting time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like).
In one embodiment, the guluronic acid oligosaccharide is a linear polysaccharide of alpha-1, 4-L guluronic acid and beta-1, 4-D-mannuronic acid linked by a 1.fwdarw.4 glycosidic bond; the sodium alginate is formed by connecting beta-D-mannuronic acid and alpha-L-guluronic acid according to a (1-4) bond.
The oligosaccharide atomizing agent based on the guluronic acid oligosaccharide, which is provided by the invention, has high deposition rate in the lung, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the antibiotic sterilization efficacy, wherein the guluronic acid oligosaccharide can damage the structure and the integrity of the sputum by changing the assembly mode of macromolecular substances in mucus, can generate a plurality of small holes to penetrate the inside and the outside of the sputum, greatly reduce the elasticity, the viscosity and the like of the sputum, and further thin, break and conveniently and smoothly discharge the sputum of a patient. In addition, the application can also enhance humoral immunity and cellular immunity, directly or indirectly inhibit the replication of viruses such as influenza A (H1N 1) and the like, and promote cell death by promoting aggregation of pathogenic bacteria and disruption of biological membranes, can effectively avoid the formation of drug-resistant bacteria, can also omnidirectionally inhibit the effect of inflammatory reaction besides the direct antibacterial effect, and can relieve the pain of patients. Furthermore, the guluronic acid oligosaccharide in the components of the application plays a role in mild and non-irritating role, which is very beneficial to the treatment of respiratory diseases including chronic obstructive pneumonia and the like. The sodium alginate is natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, is mainly used as a stabilizer and a film forming agent, forms a thin film together with phagocytes at the damaged part of the respiratory tract, can form a protective film at the serious part of the infection in the treatment process of the respiratory tract infection, plays a role in temporarily protecting the damaged part of the mucous membrane, ensures that the damaged part of the infection is not easy to be secondarily infected, improves the treatment effect and shortens the course of the disease, has the effects of moisturizing and moisturizing, has the effects of resisting free radical oxidation, inhibiting bacteria, diminishing inflammation, resisting viruses and resisting coagulation, can keep the damaged part of the mucous membrane lubricated, prevents phlegm invasion, and can promote wound healing while providing a warm and moist environment for the formation of new mucous membrane. In addition, the atomization preparation can better excite functions through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist virus, resist free radical oxidation, activate cells and remove heavy metals, so that the atomization preparation not only can well treat respiratory tract infection diseases of patients, but also is helpful for recovery after recovery of pulmonary diseases of the patients, activating pulmonary functions, and is very helpful for cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps S11-S13:
s11, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S12, adding the guluronic acid oligosaccharide with the given weight into the sodium alginate-sodium chloride solution obtained in the step S11, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide is a component which is very soluble in water, the guluronic acid oligosaccharide with a given weight is added into a sufficient amount of sodium alginate-sodium chloride solution, the solution is rapidly dissolved, insoluble impurities are separated, and a purer mixed solution can be obtained through filtration, so that the impurities can be removed for an atomized preparation.
And S13, keeping the temperature of the mixed filtrate in the step S12 constant, evaporating redundant distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S11 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S11 with sodium bicarbonate.
In one embodiment, step S11 heats the distilled/purified water to a temperature between 80℃and 90 ℃.
In one embodiment, the preparation method further comprises a step S14 of standing the atomizing agent obtained in the step S13 in an alternating magnetic field for 0.5-1.5 hours.
In one embodiment, the preparation method further comprises a step S15 of filling the atomizing agent obtained in the step S14 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S13 to step S14.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S13 with acetic acid.
In one embodiment, the preparation method further comprises a step S12 of adding the predetermined weight of the guluronic acid oligosaccharide into a sufficient amount of distilled water/purified water, stirring, filtering to obtain a guluronic acid oligosaccharide solution, and then adding the obtained guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S11 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
The application also provides another oligosaccharide atomizing agent based on guluronic acid oligosaccharide, which has good treatment effect on edema caused by inflammation and also has promotion effect on enhancing the radiation resistance of organisms besides the effects.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The components have high intrapulmonary deposition rate of guluronic acid oligosaccharide, have multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, and can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of sputum by changing the assembly mode of macromolecular substances in mucus, and can generate a plurality of small holes penetrating the inside and outside of the sputum, so that the elasticity, viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently and smoothly discharged. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of the influenza A (H1N 1) through respiratory tracts, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the treatment does not promote the recovery of the respiratory tract functions, the guluronic acid oligosaccharide in the composition can enhance humoral immunity and cellular immunity, directly or indirectly inhibit the replication of the viruses such as the influenza A (H1N 1) and the like, the pain of the patients can be relieved, and the guluronic acid oligosaccharide in the composition can effectively avoid the formation of drug resistant bacteria by promoting the aggregation and disintegration of biological membranes and accelerate the death of cells, and besides the direct antibacterial effect, the mechanism of the drug resistant oligosaccharide can also inhibit inflammatory reaction in an all-around manner, and the mechanism is as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharide in the components of the application plays a role in mild and non-irritating role, which is very beneficial to the treatment of respiratory diseases including chronic obstructive pneumonia and the like. Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum. In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.002% -0.005%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.05% -0.8%; sodium alginate: 0.02% -0.5%; carrageenan oligosaccharides: 0.0025% -0.01%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.08% -0.5%; sodium alginate: 0.05% -0.8%; carrageenan oligosaccharides: 0.005% -0.008%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.02% -0.1%; sodium alginate: 0.01% -0.025%; carrageenan oligosaccharides: 0.0015% -0.004%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the guluronic acid oligosaccharide is a linear polysaccharide of alpha-1, 4-L guluronic acid and beta-1, 4-D-mannuronic acid linked by a 1.fwdarw.4 glycosidic bond; the sodium alginate is formed by connecting beta-D-mannuronic acid and alpha-L-guluronic acid according to a (1-4) bond.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened. Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful. Besides, the sodium alginate of the atomization agent can also form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the action time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like). In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps of S21-S23:
s21, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S22, adding carrageenan oligosaccharide and guluronic acid oligosaccharide with given weights into the sodium alginate-sodium chloride solution obtained in the step S21, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide and the carrageenan oligosaccharide are all water-soluble components, the predetermined weight of the carrageenan oligosaccharide and the guluronic acid oligosaccharide are added into a sufficient amount of sodium alginate-sodium chloride solution, the solution is rapidly dissolved, insoluble impurities are separated, and a purer mixed solution can be obtained through filtration, so that the impurities can be removed for an atomized preparation.
And S23, keeping the temperature of the mixed filtrate in the step S22 constant, evaporating redundant distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S21 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S21 with sodium bicarbonate.
In one embodiment, step S21 heats the distilled/purified water to a temperature between 80 ℃ and 90 ℃.
In one embodiment, the preparation method further comprises a step S24 of standing the atomizing agent obtained in the step S23 in an alternating magnetic field for 0.5-1.5 hours.
In one embodiment, the preparation method further comprises a step S25 of filling the atomizing agent obtained in the step S24 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S23 and step S24.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S23 with acetic acid.
In one embodiment, the preparation method further includes a step S22 of adding predetermined weight of carrageenan oligosaccharide and guluronic acid oligosaccharide into sufficient distilled water/purified water, stirring, filtering to obtain a carrageenan oligosaccharide-guluronic acid oligosaccharide solution, and adding the obtained carrageenan oligosaccharide-guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S21 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
According to the above, the present application also provides an oligosaccharide atomizer based on guluronic acid oligosaccharide doped with a larger dose of carrageenan oligosaccharide to cope with severe edema or severe abnormal hyperplasia, but the administration period needs to be controlled, and the administration period is generally controlled to be no more than 2 weeks continuously, and the daily administration dose is no more than 25ml.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.5% -5.0%; sodium alginate: 0.5% -5.0%; carrageenan oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.5% -5.0%; sodium alginate: 0.5% -5.0%; carrageenan oligosaccharides: 0.025% -0.125%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 1.0% -2.5%; sodium alginate: 1.0% -1.5%; carrageenan oligosaccharides: 0.025% -0.125%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.8% -2.0%; sodium alginate: 0.6% -1.2%; carrageenan oligosaccharides: 0.05% -0.15%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.8% -2.0%; sodium alginate: 0.6% -1.2%; carrageenan oligosaccharides: 0.1% -0.25%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
The present application also provides another oligosaccharide atomizer based on guluronic acid oligosaccharides.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The components have high intrapulmonary deposition rate of guluronic acid oligosaccharide, have multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, and can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of sputum by changing the assembly mode of macromolecular substances in mucus, and can generate a plurality of small holes penetrating the inside and outside of the sputum, so that the elasticity, viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently and smoothly discharged. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of the influenza A (H1N 1) through respiratory tracts, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the treatment does not promote the recovery of the respiratory tract functions, the guluronic acid oligosaccharide in the composition can enhance humoral immunity and cellular immunity, directly or indirectly inhibit the replication of the viruses such as the influenza A (H1N 1) and the like, the pain of the patients can be relieved, and the guluronic acid oligosaccharide in the composition can effectively avoid the formation of drug resistant bacteria by promoting the aggregation and disintegration of biological membranes and accelerate the death of cells, and besides the direct antibacterial effect, the mechanism of the drug resistant oligosaccharide can also inhibit inflammatory reaction in an all-around manner, and the mechanism is as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharide in the components of the application plays a role in mild and non-irritating role, which is very beneficial to the treatment of respiratory diseases including chronic obstructive pneumonia and the like. Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum. In addition, the agar oligosaccharides as the effective components of the atomization preparation have the functions of moisture absorption and moisture retention, also have the functions of anti-inflammation, antioxidation and in-vivo free radical removal, are mainly used for protecting and diminishing inflammation of damaged parts of surface mucous membranes after being infected with the human respiratory tract together with sodium alginate, have the moisturizing function, can keep the damaged parts of the mucous membranes lubricated, prevent phlegm invasion and provide a warm and moist environment for the formation of new mucous membranes. The atomization agent also has an inhibiting effect on the development of tumors after atomization inhalation, can inhibit the growth of tumor tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.05% -0.8%; sodium alginate: 0.02% -0.5%; agar oligosaccharides: 0.03% -0.1%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.08% -0.5%; sodium alginate: 0.05% -0.8%; agar oligosaccharides: 0.05% -0.08%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 1.0% -2.5%; sodium alginate: 0.8% -2.0%; agar oligosaccharides: 0.15% -0.25%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 1.0% -2.5%; sodium alginate: 0.8% -2.0%; agar oligosaccharides: 0.2% -0.4%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 1.5% -2.0%; sodium alginate: 1.0% -1.8%; agar oligosaccharides: 0.12-0.18%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 1.8% -2.4%; sodium alginate: 1.2% -1.8%; agar oligosaccharides: 0.3% -0.35%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened. Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful. Besides, the sodium alginate of the atomization agent can also form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the action time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like). In addition, the agar oligosaccharides as the effective components of the atomization preparation have the functions of moisture absorption and moisture retention, also have the functions of anti-inflammation, antioxidation and in-vivo free radical removal, are mainly used for protecting and diminishing inflammation of damaged parts of surface mucous membranes after being infected with the human respiratory tract together with sodium alginate, have the moisturizing function, can keep the damaged parts of the mucous membranes lubricated, prevent phlegm invasion and provide a warm and moist environment for the formation of new mucous membranes. The atomization agent also has an inhibiting effect on the development of tumors after atomization inhalation, can inhibit the growth of tumor tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps S31-S33:
s31, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S32, adding the agar oligosaccharide and the guluronic acid oligosaccharide with the given weights into the sodium alginate-sodium chloride solution obtained in the step S31, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide is a component which is easy to dissolve in water, the guluronic acid oligosaccharide with a given weight is added into a sufficient amount of sodium alginate-sodium chloride solution, the solution is quickly dissolved, insoluble impurities are separated, the agar is used as marine polysaccharide, the viscosity is high, the water solubility is low, the agar is not easy to absorb, but the degraded agar oligosaccharide has good water solubility and is favorable for human absorption, the agar oligosaccharide with a given weight is added into the sufficient amount of sodium alginate-sodium chloride solution, and a purer mixed solution can be obtained through filtration, so that the impurities can be removed for an atomized preparation.
And S33, keeping the temperature of the mixed filtrate in the step S32 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S31 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S31 with sodium bicarbonate.
In one embodiment, step S31 heats the distilled/purified water to a temperature between 80℃and 90 ℃.
In one embodiment, the preparation method further comprises a step S34 of standing the atomizing agent obtained in the step S33 in an alternating magnetic field for 0.5-1.5 hours.
In one embodiment, the preparation method further comprises a step S35 of filling the atomizing agent obtained in the step S34 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S33 to step S34.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S33 with acetic acid.
In one embodiment, the preparation method further includes a step S32 of adding the predetermined weight of the agaragar oligosaccharide and the guluronic acid oligosaccharide into a sufficient amount of distilled water/purified water, stirring, filtering to obtain an agaragar oligosaccharide-guluronic acid oligosaccharide solution, and adding the obtained agaragar oligosaccharide-guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S31 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
According to the above, the present application also provides an oligosaccharide atomization agent based on guluronic acid oligosaccharide, which has good therapeutic effect on edema caused by inflammation, and also has promotion effect on enhancing the radiation resistance and anti-tumor of the organism.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The components have high intrapulmonary deposition rate of guluronic acid oligosaccharide, have multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, and can effectively reduce the viscoelasticity of sputum, damage the drug-resistant bacteria biomembrane and enhance the sterilizing efficacy of antibiotics in respiratory diseases. Among them, the increased viscosity of patient sputum is mainly due to the fact that glycoprotein molecules are cross-linked together by means of different bonds (such as disulfide bonds, hydrogen bonds, etc.), forming a gel network. And the sputum contains electrolyte, wherein the content of Ca2+ is high, and the viscosity can be increased. In the case of respiratory tract infection, DNA generated by the nuclear destruction of a large number of inflammatory cells also significantly increases the viscosity of sputum, and so-called purulent sputum is formed, which is not easily excreted. The guluronic acid oligosaccharide can destroy the structure and integrity of sputum by changing the assembly mode of macromolecular substances in mucus, and can generate a plurality of small holes penetrating the inside and outside of the sputum, so that the elasticity, viscosity and the like of the sputum are greatly reduced, and further the sputum of a patient is thinned, broken and conveniently and smoothly discharged. In addition, respiratory diseases of many patients are caused by viruses, such as fever, cough, pharyngalgia, headache, coldness, fatigue and other symptoms of the patients caused by the transmission of the influenza A (H1N 1) through respiratory tracts, the conventional treatment is antipyretic treatment and antibiotic treatment, the side effects are large, the treatment does not promote the recovery of the respiratory tract functions, the guluronic acid oligosaccharide in the composition can enhance humoral immunity and cellular immunity, directly or indirectly inhibit the replication of the viruses such as the influenza A (H1N 1) and the like, the pain of the patients can be relieved, and the guluronic acid oligosaccharide in the composition can effectively avoid the formation of drug resistant bacteria by promoting the aggregation and disintegration of biological membranes and accelerate the death of cells, and besides the direct antibacterial effect, the mechanism of the drug resistant oligosaccharide can also inhibit inflammatory reaction in an all-around manner, and the mechanism is as follows: guluronic acid oligosaccharide inhibits the combination of lipopolysaccharide (LPS, also called endotoxin) and host TLR, inhibits the activity of lipopolysaccharide on NF-KB and MAP kinase, reduces the concentration level of inflammatory mediators (NOPGE 2 and ROS) and inflammatory factors (TNF-a, IL-1 beta and IL-6) induced by lipopolysaccharide, and thus achieves the effects of resisting bacteria and diminishing inflammation. Furthermore, the guluronic acid oligosaccharide in the components of the application plays a role in mild and non-irritating role, which is very beneficial to the treatment of respiratory diseases including chronic obstructive pneumonia and the like. Sodium alginate, which is a natural polysaccharide, has excellent biocompatibility, biodegradability and bioadhesion, and is mainly used as a stabilizer and a film forming agent in the present application. The respiratory tract of a human body is damaged easily after being infected, so that the surface mucous membrane is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, in order to solve the problem, sodium alginate and guluronic acid oligosaccharide in the application can form a thin film together with phagocytes at the damaged part of the respiratory tract after being atomized and inhaled, a protective film can be formed at the serious part of the infection in the treatment process of the respiratory tract infection, the effect of temporarily protecting the damaged part of the mucous membrane is achieved, the damaged part of the infection is not easy to be subjected to secondary infection, the treatment effect is improved, the disease course is shortened, and film forming substances can not be absorbed by the human body, can fall off from a new mucous membrane after the new mucous membrane is generated, and are dissolved, and are discharged together with sputum. In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Meanwhile, the compound preparation also has an inhibiting effect on the development of tumors, can inhibit the growth of tumor cells and tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.05% -0.8%; sodium alginate: 0.02% -0.5%; carrageenan oligosaccharides: 0.0015% -0.005%; agar oligosaccharides: 0.015% -0.05%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. By the arrangement, the effective components in the oligosaccharide aerosol have better treatment effects on treating upper respiratory tract and lower respiratory tract diseases and diluting sputum, and the size of the aerosol particles is more suitable for deeper inhalation, so that the lung deposition rate of the lower respiratory tract is improved.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.08% -0.5%; sodium alginate: 0.05% -0.8%; carrageenan oligosaccharides: 0.0025% -0.004%; agar oligosaccharides: 0.025% -0.04%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance. The arrangement ensures that the effective components in the oligosaccharide atomizing agent have better treatment effect on treating upper respiratory tract infection, inflammation and sore throat.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.002% -0.005%; agar oligosaccharides: 0.018% -0.025%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.05% -0.8%; sodium alginate: 0.02% -0.5%; carrageenan oligosaccharides: 0.0025% -0.01%; agar oligosaccharides: 0.012% -0.024%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.25% -0.35%; sodium alginate: 0.015% -0.3%; carrageenan oligosaccharides: 0.003% -0.0045%; agar oligosaccharides: 0.015% -0.05%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the topical wipes of the present application also inhibit replication of Herpes Simplex Virus (HSV), thereby aiding in the treatment and recovery of infectious skin diseases caused by herpes simplex virus.
In one embodiment, the aerosol can also play a good role in inhibiting the replication of Human Papilloma Virus (HPV), hepatitis B virus and other viruses.
In each of the above examples, since sodium alginate is an anionic compound, it has an electrostatic adsorption effect on cations. Therefore, after the atomization agent is atomized and inhaled, metal ions deposited on the lung wall of a patient can be well adsorbed, the removal of heavy metals from the lung is promoted, and meanwhile, the effects of resisting free radical oxidation, inhibiting bacteria and diminishing inflammation can be achieved. In addition, the atomization agent has certain film forming property after being atomized and inhaled. After the respiratory tract of the human body is infected, the surface mucous membrane is easy to damage, so that the respiratory tract is easy to be subjected to secondary infection, even in the treatment process, various pathogenic microorganisms and pathogens can directly attack the human body without being blocked by the mucous membrane, the disease course is prolonged or other diseases are generated, if a protective film is formed at the damaged part or the weak part of the mucous membrane, the weak mucous membrane caused by infection can be effectively protected from being damaged, the temporary mucous membrane protection function is realized, the part infected by the damaged mucous membrane is not easy to be subjected to secondary infection, the treatment effect is improved and the disease course is shortened. Through the synergistic effect of the components of the atomization preparation, the efficacy of the components and the biological functions of a human body (such as activating an immune system) can be better excited, and particularly, pulmonary fibrosis resistance, bacteriostasis, inflammation resistance, virus resistance, free radical oxidation resistance, cell activation and heavy metal elimination can be better realized, so that respiratory tract infection diseases of patients can be well treated, the recovery after the recovery of the pulmonary diseases of the patients is facilitated, and the activation of the pulmonary functions and the cleaning and maintenance of the conventional lungs are very helpful. Besides, the sodium alginate of the atomization agent can also form hundreds of millions of microcapsules with drug carrying capacity with oligosaccharide with positive charges, such as chitosan and the like, through film forming property and electrostatic action, so that the oligosaccharide atomization agent of the embodiment can be used as a drug dispensing agent to interact with other agents to form drug carrying microcapsules besides the effects of the self components, and can be used for carrying other agents to treat respiratory tract infection parts, different therapeutic agent prescriptions can be added for various respiratory tract diseases, so that the disease range of the respiratory tract diseases treated by the atomization agent is widened, the carried agents are slowly released along with the dissolution of the microcapsules in the microcapsule carrier, the action time of the carried agents can be effectively prolonged, the effective concentration of the agents can be maintained, and the effect of treating respiratory tract infection is improved, and the effect of shortening the disease course is very helpful (such as carrying antibiotics and the like). In addition, the effective component carrageenan oligosaccharide of the atomization preparation has the effect of inhibiting the growth of blood vessels, can well play a role in preventing the formation of blood vessels in the case stage of abnormal hyperplasia of blood vessels, therefore, the atomization preparation has a good treatment effect on edema caused by inflammation after atomization inhalation, has a good promotion effect on enhancing the radiation resistance of organisms, can effectively prevent abnormal hyperplasia of blood vessels in the case stage, can reduce the incidence rate of lung cancer, can inhibit the growth of cancer cell tissues in the treatment process of lung cancer, achieves the effects of treating and delaying the illness state, has little toxicity on cells due to low concentration carrageenan oligosaccharide (less than 250 mug/ml), and can play a good role in treating and protecting health for various respiratory diseases due to the cooperation of other effective components in the atomization preparation. Meanwhile, the compound preparation also has an inhibiting effect on the development of tumors, can inhibit the growth of tumor cells and tissues, and achieves the effects of treating and delaying the illness state. Besides the remarkable effects, the atomization preparation can better excite the functions of a living organism through the synergistic effect of the components, and particularly can better resist pulmonary fibrosis, inhibit bacteria, diminish inflammation, resist viruses, resist free radical oxidation, activate cells and remove heavy metals, thereby not only being capable of well treating respiratory tract infection diseases of patients, but also being beneficial to recovery after recovery of pulmonary diseases of patients, activating pulmonary functions, and being very helpful to cleaning and maintaining conventional lungs.
The application also provides a preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide in each embodiment, which specifically comprises the following steps S41-S43:
s41, adding sodium alginate and sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution; generally, distilled water/purified water with the weight being 2-3 times of the given weight is stirred to obtain a sodium alginate-sodium chloride solution with enough amount, on one hand, the dissolution of each component and the filtration of impurities can be facilitated, and on the other hand, the preparation with different concentrations can be obtained by reprocessing the solution as a stock solution in the later period. In this step, since sodium alginate is slightly soluble in water and is dissolved in water to form a viscous liquid, the solubility increases and the viscosity of the solution can be lowered when heated to 80 ℃ or higher, facilitating dissolution and filtration.
S42, adding carrageenan oligosaccharide, agar oligosaccharide and guluronic acid oligosaccharide with given weights into the sodium alginate-sodium chloride solution obtained in the step S41, stirring, and filtering to obtain a mixed solution; in the step, the guluronic acid oligosaccharide and the carrageenan oligosaccharide are water-soluble components, the predetermined weight of the guluronic acid oligosaccharide and the carrageenan oligosaccharide are added into a sufficient amount of sodium alginate-sodium chloride solution, the guluronic acid oligosaccharide and the carrageenan oligosaccharide are rapidly dissolved, insoluble impurities are separated, the agar is used as a marine polysaccharide, the viscosity is high, the water solubility is low, the agar is not easily absorbed, but the degraded agar oligosaccharide has good water solubility and is favorable for human absorption, the predetermined weight of the agar oligosaccharide is added into a sufficient amount of sodium alginate-sodium chloride solution, the rapid dissolution is also achieved, the insoluble impurities are also separated, and thus, a purer mixed solution can be obtained through filtration, and the impurities can be removed for an atomized preparation.
And S43, keeping the temperature of the mixed filtrate in the step S42 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide. The step adopts a low-temperature low-pressure evaporation mode to evaporate redundant free water, so that the concentration of the medicament can be increased, and the concentration of each component of the medicament is controlled within a preset percentage range. On the other hand, because the amphiphilic polymer is similar to the surfactant, when the concentration of the polymer is low, polymer molecules exist in the form of single molecular chains in the aqueous solution, and when the concentration is increased to be above the critical micelle concentration, the polymer can self-assemble to form polymer micelles, and the polymer is slowly concentrated from low concentration to help improve the stability of the combined components.
In one embodiment, step S41 further increases the dissolution rate of sodium alginate by adjusting the pH of the distilled/purified water to between 7.5 and 9.
In one embodiment, the method further comprises adjusting the pH of the distilled/purified water of step S41 with sodium bicarbonate.
In one embodiment, step S41 heats the distilled/purified water to a temperature between 80℃and 90 ℃.
In one embodiment, the preparation method further comprises a step S44 of standing the atomizing agent obtained in the step S43 in an alternating magnetic field for 0.5 to 1.5 hours.
In one embodiment, the preparation method further comprises a step S45 of filling the atomizing agent obtained in the step S44 into corresponding penicillin bottles or ampoule bottles in an amount of 2-2.5 ml.
In one embodiment, the preparation method further comprises adjusting the PH of the mixed filtrate to 7±0.05% between step S43 to step S44.
In one embodiment, the method further comprises adjusting the pH of the mixed solution of step S43 with acetic acid.
In one embodiment, the preparation method further includes a step S42 of adding predetermined weight of carrageenan oligosaccharide, agar oligosaccharide and guluronic acid oligosaccharide into sufficient distilled water/purified water, stirring, filtering to obtain an agar oligosaccharide-carrageenan oligosaccharide-guluronic acid oligosaccharide solution, and adding the obtained agar oligosaccharide-carrageenan oligosaccharide-guluronic acid oligosaccharide solution into the sodium alginate-sodium chloride solution obtained in the step S41 to obtain a mixed solution.
The preparation method of the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide has the advantages of simple process, easily available equipment, capability of rapidly realizing large-scale production and low production and manufacturing cost. In addition, no extra waste and pollutant are generated in the production process, and the method is more environment-friendly.
According to the above, the present application also provides an oligosaccharide atomizer based on guluronic acid oligosaccharide doped with a larger dose of carrageenan oligosaccharide to cope with severe edema or severe abnormal hyperplasia, but the administration period needs to be controlled, and the administration period is generally controlled to be no more than 2 weeks continuously, and the daily administration dose is no more than 25ml.
An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.5% -5.0%; sodium alginate: 0.5% -5.0%; agar oligosaccharides: 0.01% -0.5%; carrageenan oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.5% -5.0%; sodium alginate: 0.5% -5.0%; agar oligosaccharides: 0.1% -0.25%; carrageenan oligosaccharides: 0.025% -0.125%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 1.0% -2.5%; sodium alginate: 1.0% -1.5%; agar oligosaccharides: 0.025% -0.15%; carrageenan oligosaccharides: 0.025% -0.125%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.8% -2.0%; sodium alginate: 0.6% -1.2%; agar oligosaccharides: 0.035% -0.08%; carrageenan oligosaccharides: 0.05% -0.15%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.8% -2.0%; sodium alginate: 0.6% -1.2%; agar oligosaccharides: 0.15% -0.35%; carrageenan oligosaccharides: 0.1% -0.25%; sodium chloride: 0.1% -0.9%; distilled/purified water: the balance.
In accordance with the foregoing, the present application also provides another oligosaccharide atomizer based on guluronic acid oligosaccharides. An oligosaccharide atomizing agent based on guluronic acid oligosaccharide comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance. Under the effect of the diastole, the product has the functions of dilating bronchi, relieving bronchus smooth muscle and relieving airflow limitation, and can well prevent the air pipe of partial people from spasm under the stimulation of drugs, thereby achieving the purposes of spasmolysis and asthma relieving, enabling the atomization agent to be deposited deeper and improving the treatment efficacy.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; distilled/purified water: the balance.
In the embodiment, under the action of the diastole agent, the atomization agent has the functions of expanding bronchi, relieving bronchus smooth muscles and relieving airflow limitation, and can well prevent the air pipes of partial people from spasm under the stimulation of medicaments, thereby achieving the purposes of spasmolysis and asthma relieving, enabling the atomization agent to be deposited deeper and improving the treatment efficacy.
In accordance with the foregoing, the present application also provides another oligosaccharide atomizer based on guluronic acid oligosaccharides. An oligosaccharide atomizer based on guluronic acid oligosaccharide, and also comprises antibacterial agent; the components of the paint comprise the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; sodium chloride: 0.1% -0.9%; bacteriostat: 0.01% -0.03%; distilled/purified water: the balance. In this embodiment, the antimicrobial agent may be an antibiotic drug. Because the pure antibiotics generally need to be metabolized by the liver to act, the antibiotics have low fat solubility and high water solubility, are less combined with the mucous membrane tissues of the lung airway, have low deposition rate in the lung, have low affinity with glucocorticoid receptor, have short residence time in the airway, are difficult to exert local anti-inflammatory effect by aerosol inhalation, and have poor curative effect. The guluronic acid oligosaccharide has high intrapulmonary deposition rate, has multiple biological activities of immunoregulation, anti-inflammation, nerve protection, drug-resistant bacteria biomembrane damage and the like, can effectively reduce the viscoelasticity of sputum in respiratory diseases, and can be completely carried and co-deposited at focus positions after being atomized by adding the antibacterial agent with the predetermined amount in the scheme, thereby playing a role in synergy, and further achieving better treatment effect.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; sodium chloride: 0.1% -0.9%; bacteriostat: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; bacteriostat: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; bacteriostat: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the oligosaccharide atomizing agent based on the guluronic acid oligosaccharides comprises the following components in percentage by weight: guluronic acid oligosaccharides: 0.01% -5.0%; sodium alginate: 0.01% -5.0%; carrageenan oligosaccharides: 0.001% -0.05%; agar oligosaccharides: 0.01% -0.5%; sodium chloride: 0.1% -0.9%; diastole agent: 0.01% -0.05%; bacteriostat: 0.01% -0.03%; distilled/purified water: the balance.
In one embodiment, the diastolic agent is at least one of albuterol, terbutaline, ipratropium bromide.
In one embodiment, the antimicrobial agent is at least one of gentamicin, amikacin, vancomycin.
In one embodiment, the albuterol is an inhalation albuterol sulfate solution.
In one embodiment, terbutaline is terbutaline sulfate nebulized solution.
In one embodiment, the ipratropium bromide is an ipratropium bromide aerosol inhalation solution.
In one embodiment, gentamicin is adopted as gentamicin injection, gentamicin tablets or gentamicin liquid is adopted directly, and the gentamicin injection is low in cost and easy to obtain.
In one embodiment, amikacin is a crystalline powder of amikacin, or an aqueous solution of amikacin dissolved in distilled water in a specific ratio.
In one embodiment, vancomycin is a vancomycin powder or a solution obtained by adding vancomycin powder to water for injection.
In one embodiment, the antimicrobial agent comprises a dialkyl quaternary ammonium salt and chlorhexidine acetate in equal weight percentages.
The technical features of the above embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The foregoing examples represent only a few embodiments of the present application, which are described in more detail and are not to be construed as limiting the scope of the claims. It should be noted that it would be apparent to those skilled in the art that various modifications and improvements could be made without departing from the spirit of the present application, which would be within the scope of the present application. Accordingly, the scope of protection of the present application is to be determined by the claims appended hereto.
Claims (16)
1. An oligosaccharide atomizing agent based on guluronic acid oligosaccharide is characterized by comprising the following components in percentage by weight:
guluronic acid oligosaccharides: 0.01% -5.0%;
sodium alginate: 0.01% -5.0%;
sodium chloride: 0.1% -0.9%; and
distilled/purified water: the balance.
2. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 1, wherein the components thereof include in weight percent:
The guluronic acid oligosaccharide: 0.05% -0.8%;
the sodium alginate comprises the following components: 0.02% -0.5%;
the sodium chloride: 0.1% -0.9%; and
the distilled/purified water: the balance.
3. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 1, wherein the components thereof include in weight percent:
the guluronic acid oligosaccharide: 0.08% -0.5%;
the sodium alginate comprises the following components: 0.05% -0.8%;
the sodium chloride: 0.1% -0.9%;
the distilled/purified water: the balance.
4. A process for the preparation of an oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in any one of claims 1 to 3, characterized in that said preparation process comprises in particular the following steps:
s11, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution;
s12, adding the guluronic acid oligosaccharide with the given weight into the sodium alginate-sodium chloride solution obtained in the step S11, stirring, and filtering to obtain a mixed solution;
and S13, keeping the temperature of the mixed filtrate in the step S12 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide.
5. An oligosaccharide atomizing agent based on guluronic acid oligosaccharide is characterized by comprising the following components in percentage by weight:
guluronic acid oligosaccharides: 0.01% -5.0%;
sodium alginate: 0.01% -5.0%;
carrageenan oligosaccharides: 0.001% -0.05%;
sodium chloride: 0.1% -0.9%; and
distilled/purified water: the balance.
6. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 5, wherein the components thereof include in weight percent:
the guluronic acid oligosaccharide: 0.05% -0.8%;
the sodium alginate comprises the following components: 0.02% -0.5%;
the carrageenan oligosaccharides: 0.0025% -0.01%;
the sodium chloride: 0.1% -0.9%; and
the distilled/purified water: the balance.
7. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 5, wherein the components thereof include in weight percent:
the guluronic acid oligosaccharide: 0.08% -0.5%;
the sodium alginate comprises the following components: 0.05% -0.8%;
the carrageenan oligosaccharides: 0.005% -0.008%;
the sodium chloride: 0.1% -0.9%;
the distilled/purified water: the balance.
8. Process for the preparation of an oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in any of claims 5 to 7, characterized in that said process comprises in particular the following steps:
S21, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution;
s22, adding carrageenan oligosaccharide and guluronic acid oligosaccharide with given weights into the sodium alginate-sodium chloride solution obtained in the step S21, stirring, and filtering to obtain a mixed solution;
and S23, keeping the temperature of the mixed filtrate in the step S22 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide.
9. An oligosaccharide atomizing agent based on guluronic acid oligosaccharide is characterized by comprising the following components in percentage by weight:
guluronic acid oligosaccharides: 0.01% -5.0%;
sodium alginate: 0.01% -5.0%;
agar oligosaccharides: 0.01% -0.5%;
sodium chloride: 0.1% -0.9%; and
distilled/purified water: the balance.
10. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 9, wherein the components thereof include in weight percent:
the guluronic acid oligosaccharide: 0.05% -0.8%;
The sodium alginate comprises the following components: 0.02% -0.5%;
the agar oligosaccharides: 0.03% -0.1%;
the sodium chloride: 0.1% -0.9%; and
the distilled/purified water: the balance.
11. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 9, wherein the components thereof include in weight percent:
the guluronic acid oligosaccharide: 0.08% -0.5%;
the sodium alginate comprises the following components: 0.05% -0.8%;
the agar oligosaccharides: 0.05% -0.08%;
the sodium chloride: 0.1% -0.9%;
the distilled/purified water: the balance.
12. Process for the preparation of an oligosaccharide atomizing agent based on guluronic acid oligosaccharides according to any of claims 9-11, characterized in that the preparation process comprises in particular the following steps:
s31, adding the sodium alginate and the sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution;
s32, adding the agar oligosaccharide and the guluronic acid oligosaccharide with the given weights into the sodium alginate-sodium chloride solution obtained in the step S31, stirring, and filtering to obtain a mixed solution;
and S33, keeping the temperature of the mixed filtrate in the step S32 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide.
13. An oligosaccharide atomizing agent based on guluronic acid oligosaccharide is characterized by comprising the following components in percentage by weight:
guluronic acid oligosaccharides: 0.01% -5.0%;
sodium alginate: 0.01% -5.0%;
carrageenan oligosaccharides: 0.001% -0.05%;
agar oligosaccharides: 0.01% -0.5%;
sodium chloride: 0.1% -0.9%; and
distilled/purified water: the balance.
14. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 13, wherein the components thereof include in weight percent:
the guluronic acid oligosaccharide: 0.05% -0.8%;
the sodium alginate comprises the following components: 0.02% -0.5%;
the carrageenan oligosaccharides: 0.0015% -0.005%;
the agar oligosaccharides: 0.015% -0.05%;
the sodium chloride: 0.1% -0.9%; and
the distilled/purified water: the balance.
15. The oligosaccharide atomizing agent based on guluronic acid oligosaccharides as claimed in claim 13, wherein the components thereof include in weight percent:
the guluronic acid oligosaccharide: 0.08% -0.5%;
the sodium alginate comprises the following components: 0.05% -0.8%;
the carrageenan oligosaccharides: 0.0025% -0.004%;
the agar oligosaccharides: 0.025% -0.04%;
The sodium chloride: 0.1% -0.9%;
the distilled/purified water: the balance.
16. Process for the preparation of an oligosaccharide atomizing agent based on guluronic acid oligosaccharides according to any of claims 13 to 15, characterized in that the process comprises in particular the following steps:
s41, adding sodium alginate and sodium chloride with given weights into enough distilled water/purified water with the temperature of more than 80 ℃, stirring, and filtering to obtain sodium alginate-sodium chloride solution;
s42, adding carrageenan oligosaccharide, agar oligosaccharide and guluronic acid oligosaccharide with given weights into the sodium alginate-sodium chloride solution obtained in the step S41, stirring, and filtering to obtain a mixed solution;
and S43, keeping the temperature of the mixed filtrate in the step S42 constant, evaporating excessive distilled water/purified water to a preset amount under low pressure, degassing, cooling to room temperature, and controlling the vacuum degree under low pressure to be 0.5-0.75bar to obtain the oligosaccharide atomizing agent based on the guluronic acid oligosaccharide.
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