Application of compound folium isatidis injection in atomization and rectal administration and preparation method of compound folium isatidis injection

Abstract

The invention discloses application of a compound folium isatidis injection in atomization and rectal administration and a preparation method of the compound folium isatidis injection. 0.2-0.3% by mass of an osmotic pressure regulator is added into the compound folium isatidis injection to obtain the compound folium isatidis injection added with the osmotic pressure regulator; adjusting the pH value of the obtained compound folium isatidis injection added with the osmotic pressure regulator to 6.3-6.8 by using a pH regulator; the solution regulated by the pH regulator is prepared into an atomization inhalant by using ultrasonic waves or a compression type atomization machine, and the atomization inhalant is directly inhaled into a respiratory system in an atomization mode or covers the respiratory system in a local spraying mode; a rectal absorption enhancer with the mass fraction of 0.2-0.3% is added into the compound folium isatidis injection, the pH value and the osmotic pressure of the prepared atomized liquid medicine and spray liquid medicine meet the physicochemical property requirements of the respiratory system and the intestinal environment, and the rectal administration preparation has no irritation to the respiratory tract and has no toxic or side effect. The prepared medicine is applied to a patient for treatment through corresponding medical equipment.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of compound isatis leaf extract, and particularly relates to application of compound isatis leaf injection in atomization and rectal administration and a preparation method thereof. Background Art

[0002] Influenza, or flu for short, is an acute respiratory infectious disease caused by influenza virus. It is highly contagious and usually spreads rapidly in crowded places, such as schools, offices, and nursing homes. Influenza viruses are highly variable, so they may cause epidemics of varying sizes every year. Influenza is mainly caused by influenza viruses, including influenza A, B, and C viruses. Among them, influenza A virus is most likely to mutate, so it often causes a global pandemic. Influenza B virus also has a certain degree of variability. An effective way to prevent influenza is to get a flu vaccine, especially for high-risk groups, such as the elderly, children, pregnant women, and patients with chronic diseases. In addition, maintaining good personal hygiene habits, such as washing hands frequently, wearing masks, and avoiding crowded places, can also help prevent influenza; for influenza patients, treatment mainly includes rest, adequate water intake, and drug therapy. Antiviral drugs (such as oseltamivir, zanamivir, etc.) can be used to treat influenza, but they should be used under the guidance of a doctor. For patients with severe symptoms, hospitalization may be required. Compound Daqingye injection is made of Daqingye, honeysuckle, bistort, notopterygium, rhubarb, benzyl alcohol, and sodium sulfite in a scientific ratio, using advanced process technologies such as water decoction, secondary alcohol precipitation, and double sterilization filtration. Compound Daqingye injection clears away pathogens and detoxifies, and is used for Japanese encephalitis, acute and chronic hepatitis, influenza, and mumps;

[0003] The compound isatis leaf extract has the effect of inhibiting or delaying cytopathic effects on a variety of viruses, including Japanese encephalitis virus, mumps virus, influenza virus, etc. The compound isatis leaf is often used to treat infectious diseases such as colds, influenza, viral hepatitis, and as a formula ingredient for drugs such as dispelling wind and heat, detoxifying and reducing swelling, and relieving pain. The traditional compound isatis leaf injection is administered by intramuscular injection, which has treatment risks such as injection site pain, infection, and needle breakage, and reduces patient compliance. It also contains benzyl alcohol, which is prone to gluteal muscle atrophy in children, that is, spasm and atrophy of the gluteal muscles. The main clinical manifestations of children with gluteal muscle contracture are: abnormal gait, unilateral gluteal muscle contracture with limp, bilateral parallel eight-character line, and inability to cross legs. When standing, the lower limbs are slightly externally rotated and cannot be completely closed. Squatting is limited, and the hips are in abduction and external rotation posture. The knees are separated and "frog-shaped legs". Physical examination shows that the skin at the injection site of the buttocks is sunken or the normal appearance of the buttocks disappears. Therefore, it is prohibited to be used for intramuscular injection in children.

[0004] In addition, the concentration of compound isatis leaf injection is relatively high. Although benzyl alcohol is added to have a local anesthetic effect, there is still severe injection pain after intramuscular injection, which greatly reduces the patient's adaptability to medication. Therefore, we need to provide the application of compound isatis leaf injection in nebulization and rectal administration and its preparation method. Summary of the invention

[0005] The object of the present invention is to provide the application of compound isatis leaf injection in atomization and rectal administration and its preparation method. The pH value and osmotic pressure of the atomized liquid, spray liquid and rectal administration preparation prepared in the present invention meet the physical and chemical property requirements of the respiratory system and the intestinal environment, and are not irritating to the respiratory tract. The prepared medicine is given to patients for treatment through corresponding medical equipment. Through the above different preparations, the compound isatis leaf injection is used to clinically treat diseases caused by viruses, bacteria and drug-resistant bacteria, such as Japanese encephalitis, influenza, mumps, acute and chronic hepatitis, etc., to solve the above background technology proposed that the traditional compound isatis leaf injection in the prior art is administered by intramuscular injection, which has the risks of injection site pain, infection, needle breakage and the like, and reduces the patient's compliance. And it contains benzyl alcohol, which is easy to cause gluteal muscle atrophy in children after intramuscular injection, that is, gluteal muscle spasm and atrophy. The main clinical manifestations of children with gluteal muscle contracture are: abnormal gait, unilateral gluteal muscle contracture with limp, bilateral parallel eight-character line, and cannot cross legs. When standing, the lower limbs are slightly externally rotated and cannot be completely closed. Squatting is limited, and the hips are in abduction and external rotation. The knees are separated and form "frog legs". Physical examination shows that the skin at the injection site of the buttocks is sunken or the normal shape of the buttocks disappears. Therefore, it is forbidden to use it for intramuscular injection in children. In addition, the concentration of the compound isatis leaf injection is relatively high. Although benzyl alcohol is added to have a local anesthetic effect, there is still severe injection pain after intramuscular injection, which greatly reduces the problem of patient adaptability to medication.

[0006] To achieve the above object, the present invention adopts the following technical scheme: the application of compound isatis leaf injection in atomization and rectal administration and the preparation method thereof, comprising the following steps:

[0007] Adding 0.2-0.3% by mass of an osmotic pressure regulator to the compound isatis leaf injection to obtain the compound isatis leaf injection with the osmotic pressure regulator added;

[0008] The obtained compound isatis leaf injection solution with the added osmotic pressure regulator is adjusted to a pH value of 6.3-6.8 with a pH regulator;

[0009] The solution adjusted with the pH adjusting agent is made into an aerosol inhalation agent by using an ultrasonic or compression nebulizer, and is directly inhaled into the respiratory system in the form of aerosol or covered with the respiratory system by local spraying;

[0010] Adding 0.2-0.3% by mass of a rectal absorption enhancer to the compound isatis leaf injection, and adjusting the pH value to 6.3-6.8 with a pH adjuster;

[0011] The obtained solution is made into a rectal administration preparation or placed into a dropper to make a rectal drip irrigation preparation, which is absorbed through the rectal mucosa and enters the venous blood circulation.

[0012] Preferably, the osmotic pressure regulator is one of sodium chloride, glucose and mannitol.

[0013] Preferably, the rectal absorption enhancer is one of salicylic acid, 5-hydroxymethylsalicylic acid, surfactants, amines and their derivatives, and fatty acids.

[0014] Preferably, the pH adjuster is one or more of hydrochloric acid, sodium hydroxide, sodium carbonate, sodium citrate, and sodium tartrate.

[0015] Technical effects and advantages of the present invention: The application of the compound isatis leaf injection in atomization and rectal administration and the preparation method thereof proposed by the present invention have the following advantages compared with the prior art:

[0016] The technical effects and advantages of the present invention are as follows: the pH value and osmotic pressure of the atomized liquid, spray liquid and rectal preparation prepared in the present invention meet the requirements of the physical and chemical properties of the respiratory system and the intestinal environment, have no irritation to the respiratory tract, and the prepared medicine is given to patients for treatment through corresponding medical devices and equipment; through the above different preparations, the compound isatis leaf injection is used to clinically treat diseases caused by viruses, bacteria, and drug-resistant bacteria, such as Japanese encephalitis, influenza, mumps, acute and chronic hepatitis, etc. In the preparation of the compound isatis leaf, the pH value and osmotic pressure of the atomized liquid, spray liquid and rectal preparation prepared meet the requirements of the physical and chemical properties of the respiratory system and the intestinal environment, have no irritation to the respiratory tract, and the prepared medicine is given to patients for treatment through corresponding medical devices and equipment; through the above different preparations, the compound isatis leaf injection is used to clinically treat diseases caused by viruses, bacteria, and drug-resistant bacteria, such as Japanese encephalitis, influenza, mumps, acute and chronic hepatitis, etc.

[0017] Other features and advantages of the present invention will be described in the following description, and partly become obvious from the description, or be understood by implementing the present invention. The purpose and other advantages of the present invention can be realized and obtained by the structures pointed out in the description and the drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a preparation diagram of the compound isatis leaf injection of the present invention during atomization and rectal administration. DETAILED DESCRIPTION

[0019] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0020] The present invention provides Figure 1 The application of the compound isatis leaf injection in atomization and rectal administration and the preparation method thereof are characterized in that they include the following steps:

[0021] Adding 0.2-0.3% by mass of an osmotic pressure regulator to the compound isatis leaf injection to obtain the compound isatis leaf injection with the osmotic pressure regulator added;

[0022] The obtained compound isatis leaf injection solution with the added osmotic pressure regulator is adjusted to a pH value of 6.3-6.8 with a pH regulator;

[0023] The solution adjusted with the pH adjusting agent is made into an aerosol inhalation agent by using an ultrasonic or compression nebulizer, and is directly inhaled into the respiratory system in the form of aerosol or covered with the respiratory system by local spraying;

[0024] Adding 0.2-0.3% by mass of a rectal absorption enhancer to the compound isatis leaf injection, and adjusting the pH value to 6.3-6.8 with a pH adjuster;

[0025] The obtained solution is made into a rectal administration preparation or placed into a dropper to make a rectal drip irrigation preparation, which is absorbed through the rectal mucosa and enters the venous blood circulation.

[0026] The osmotic pressure regulator is one of sodium chloride, glucose and mannitol;

[0027] Specifically, osmotic pressure regulators are mainly used in pharmaceutical preparations to adjust the osmotic pressure of solutions to ensure the stability and safety of drugs in the body. Appropriate osmotic pressure helps reduce drug stimulation and damage to tissues and improves the bioavailability and efficacy of drugs.

[0028] Function of sodium chloride: Sodium chloride is a commonly used osmotic pressure regulator that regulates osmotic pressure by increasing the ion concentration in the solution.

[0029] Safety: Sodium chloride is widely present in the human body, has good biocompatibility, and usually does not cause adverse reactions.

[0030] Stability: Sodium chloride is stable in solution and is not prone to chemical reactions, which helps maintain the stability of the drug.

[0031] Note: When adding sodium chloride, its concentration needs to be strictly controlled to avoid adverse effects on the drug.

[0032] Action of Glucose: Glucose is a non-electrolyte osmotic pressure regulator that regulates osmotic pressure by increasing the solute concentration in the solution.

[0033] Safety: Glucose is one of the main energy sources in the human body and has good biocompatibility.

[0034] Stability: Glucose is relatively stable in solution, but care should be taken to avoid adverse conditions such as high temperature and light.

[0035] Note: For diabetic patients, the use of injections containing glucose requires caution.

[0036] Effect of mannitol: Mannitol is a hypertonic dehydrating agent that eliminates tissue edema by increasing plasma osmotic pressure.

[0037] Safety: Mannitol is metabolized rapidly in the human body and usually does not cause serious adverse reactions.

[0038] Stability: Mannitol is stable in solution, but care should be taken to avoid incompatibility with certain drugs.

[0039] Note: Mannitol has a high osmotic pressure, so the concentration and dosage need to be strictly controlled when used to avoid causing mild diarrhea.

[0040] The rectal absorption enhancer is one of salicylic acid, 5-hydroxymethyl salicylic acid, surfactants, amines and their derivatives, and fatty acids;

[0041] Specifically, the mechanism of action of salicylic acid and 5-methoxysalicylic acid: salicylic acid and its derivatives can increase the permeability of the rectal mucosa, thereby promoting the absorption of drugs. They can interact with certain components in the rectal mucosa, change the permeability of the membrane, and make drugs pass more easily.

[0042] Application example: Adding salicylic acid or 5-methoxysalicylic acid to the rectal delivery system of insulin can significantly improve the absorption efficiency and bioavailability of insulin.

[0043] Mechanism of action of surfactants: Surfactants can increase the hydrophilicity of drugs, improve the wettability and spreading of drugs on the rectal mucosa, and they can also interact with the lipid layer on the rectal mucosa, destroying the integrity of the lipid layer, thereby promoting the absorption of drugs.

[0044] Application example: Adding surfactants such as Labrasol (caprylic acid / capric acid PEG-8 glyceride) to certain rectal suppositories can significantly improve the absorption efficiency of the drug.

[0045] Mechanism of action of amines and their derivatives: Amines and their derivatives can change the charge state of the rectal mucosa and increase the permeability of drugs. They can also interact with certain receptors on the rectal mucosa to promote drug absorption.

[0046] Application example: In some rectal drug delivery systems, the use of enamine derivatives such as sodium D-glycinate, sodium D-leucine, sodium D-phenylalanine, etc. as absorption enhancers can significantly improve the bioavailability of drugs.

[0047] Mechanism of action of fatty acids: Fatty acids can increase the fluidity of the rectal mucosa, making it easier for drugs to pass through. They can also interact with the lipid layer on the rectal mucosa to promote drug absorption.

[0048] Application example: Adding fatty acids such as caprylic acid and capric acid to certain rectal suppositories can significantly improve the absorption efficiency of the drug.

[0049] The pH regulator is one or more of hydrochloric acid, sodium hydroxide, sodium carbonate, sodium citrate, and sodium tartrate;

[0050] Specifically, hydrochloric acid acts as a strong acidic substance, mainly used to reduce the pH value of the system; sodium hydroxide acts as a strong alkaline substance, used to increase the pH value of the system; sodium carbonate acts as a pH regulator, which is used to increase the pH value of the system. The principle is that carbonate ions react with hydrogen ions to generate carbon dioxide gas and water, thereby integrating hydrogen ions in the water; sodium citrate acts as a pH regulator in the food industry to maintain the stability and taste of food. In addition, it also has emulsification, stabilization, and antiseptic effects; sodium tartrate acts as a pH regulator with antioxidant activity.

[0051] Working principle: adding an osmotic pressure regulator with a mass fraction of 0.2-0.3% to the compound isatis leaf injection to obtain the compound isatis leaf injection with the osmotic pressure regulator; adjusting the pH value of the obtained compound isatis leaf injection with the osmotic pressure regulator to 6.3-6.8 with a pH regulator; preparing the solution adjusted with the pH regulator into an atomized inhalation agent with an ultrasonic or compression atomizer, directly inhaling the respiratory system in an atomized form or covering the respiratory system through a local spraying method; adding a rectal absorption promoter with a mass fraction of 0.2-0.3% to the compound isatis leaf injection, and adjusting the pH value to 6.3-6.8 with the pH regulator; preparing the obtained solution into a rectal administration preparation or placing the obtained solution in a dropper to prepare a rectal drip irrigation preparation, which is absorbed into the venous blood circulation through the rectal mucosa.

[0052] In addition, when the above-mentioned text creation unit, image generation unit, high-quality image training unit and model optimization processing unit are executed, they are also used to realize other functions of the preparation of the above-mentioned compound isatis indigotica injection in atomization and rectal administration, which will not be elaborated here one by one.

[0053] In addition, the present invention also provides a terminal device. The application of the compound isatis indigotica injection in atomization and rectal administration and its preparation method involved in this embodiment are mainly used in the terminal device, which can be a PC, a portable computer, a mobile terminal and other devices with display and processing functions.

[0054] Specifically, the terminal device may include a processor (e.g., CPU), a communication bus, a user interface, a network interface, and a memory. The communication bus is used to realize the connection and communication between these components; the user interface may include a display screen (Display), an input unit such as a keyboard (Keyboard); the network interface may optionally include a standard wired interface, a wireless interface (such as a WI-FI interface); the memory may be a high-speed RAM memory, or a stable memory (non-volatile memory), such as a disk memory, and the memory may optionally be a storage device independent of the aforementioned processor.

[0055] Among them, the memory stores a readable storage medium, and the readable storage medium stores the application of the compound isatis leaf injection in nebulization and rectal administration and its preparation program. The processor can call the application of the compound isatis leaf injection in nebulization and rectal administration and its preparation method stored in the memory, and execute the application of the compound isatis leaf injection in nebulization and rectal administration and its preparation method provided in an embodiment of the present invention.

[0056] It is understood that a readable storage medium can be a tangible device that can hold and store instructions used by an instruction execution device. Computer-readable storage media can be, for example, but not limited to, an electrical storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the above. More specific examples of computer-readable storage media (a non-exhaustive list) include: portable computer disks, hard disks, random access memories (RAM), read-only memories (ROM), erasable programmable read-only memories (EPROM or flash memory), static random access memories (SRAM), portable compact disk read-only memories (CD-ROM), digital versatile disks (DVD), memory sticks, floppy disks, mechanical encoding devices, such as punch cards or raised structures in grooves on which instructions are stored, and any suitable combination of the above. The computer-readable storage medium used here is not to be interpreted as a transient signal itself, such as a radio wave or other freely propagating electromagnetic wave, an electromagnetic wave propagating through a waveguide or other transmission medium (e.g., a light pulse through a fiber optic cable), or an electrical signal transmitted through a wire.

[0057] The computer-readable program instructions described herein can be downloaded from a computer-readable storage medium to each computing / processing device, or downloaded to an external computer or external storage device via a network, such as the Internet, a local area network, a wide area network, and / or a wireless network. The network can include copper transmission cables, optical fiber transmissions, wireless transmissions, routers, firewalls, switches, gateway computers, and / or edge servers. The network adapter card or network interface in each computing / processing device receives the computer-readable program instructions from the network and forwards the computer-readable program instructions for storage in the computer-readable storage medium in each computing / processing device.

[0058] The computer program instructions for performing the operation of the present disclosure may be assembly instructions, instruction set architecture (ISA) instructions, machine instructions, machine-related instructions, microcode, firmware instructions, state setting data, or source code or object code written in any combination of one or more programming languages, including object-oriented programming languages, such as Smalltalk, C++, etc., and conventional procedural programming languages, such as "C" language or similar programming languages. Computer-readable program instructions may be executed completely on a user's computer, partially on a user's computer, as an independent software package, partially on a user's computer, partially on a remote computer, or completely on a remote computer or server. In the case of a remote computer, the remote computer may be connected to the user's computer via any type of network, including a local area network (LAN) or a wide area network (WAN), or may be connected to an external computer (e.g., using an Internet service provider to connect via the Internet). In some embodiments, an electronic circuit, such as a programmable logic circuit, a field programmable gate array (FPGA), or a programmable logic array (PLA), may be customized by utilizing the state information of the computer-readable program instructions, and the electronic circuit may execute the computer-readable program instructions, thereby realizing various aspects of the present disclosure.

[0059] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. The application of compound isatis leaf injection in atomization and rectal administration and its preparation method, characterized in that: The steps include: Adding 0.2-0.3% by mass of an osmotic pressure regulator to the compound isatis leaf injection to obtain the compound isatis leaf injection with the osmotic pressure regulator added; The obtained compound isatis leaf injection solution with the added osmotic pressure regulator is adjusted to a pH value of 6.3-6.8 with a pH regulator; The solution adjusted with the pH adjusting agent is made into an aerosol inhalation agent by using an ultrasonic or compression nebulizer, and is directly inhaled into the respiratory system in the form of aerosol or covered with the respiratory system by local spraying; Adding 0.2-0.3% by mass of a rectal absorption enhancer to the compound isatis leaf injection, and adjusting the pH value to 6.3-6.8 with a pH adjuster; The obtained solution is made into a rectal administration preparation or placed into a dropper to make a rectal drip irrigation preparation, which is absorbed through the rectal mucosa and enters the venous blood circulation.

2. The application of the compound isatis leaf injection in atomization and rectal administration and the preparation method thereof according to claim 1, characterized in that: The osmotic pressure regulator is one of sodium chloride, glucose and mannitol.

3. The application of the compound isatis leaf injection in atomization and rectal administration and the preparation method thereof according to claim 2, characterized in that: The rectal absorption enhancer is one of salicylic acid, 5-hydroxymethyl salicylic acid, surfactants, amines and their derivatives, and fatty acids.

4. The application of the compound isatis leaf injection in atomization and rectal administration and the preparation method thereof according to claim 1, characterized in that: The pH adjuster is one or more of hydrochloric acid, sodium hydroxide, sodium carbonate, sodium citrate, and sodium tartrate.

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