CN112716906A - Preparation method of phospholipid chitosan medicine - Google Patents
Preparation method of phospholipid chitosan medicine Download PDFInfo
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- CN112716906A CN112716906A CN202110058959.0A CN202110058959A CN112716906A CN 112716906 A CN112716906 A CN 112716906A CN 202110058959 A CN202110058959 A CN 202110058959A CN 112716906 A CN112716906 A CN 112716906A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
- B01F27/05—Stirrers
- B01F27/11—Stirrers characterised by the configuration of the stirrers
- B01F27/19—Stirrers with two or more mixing elements mounted in sequence on the same axis
- B01F27/191—Stirrers with two or more mixing elements mounted in sequence on the same axis with similar elements
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
- B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
- B01F27/90—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with paddles or arms
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/80—Mixing plants; Combinations of mixers
- B01F33/82—Combinations of dissimilar mixers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention discloses a preparation method of a phospholipid chitosan medicine, relating to the field of biological medicine, wherein the phospholipid chitosan medicine comprises the following components in parts by weight: the invention relates to a drug delivery liposome, which comprises 1-10 parts of protein polypeptide drugs, 10-100 parts of phospholipid and 1-10 parts of chitosan, wherein the phospholipid material is selected from at least one of natural phospholipid and synthetic phospholipid, and the chitosan is selected from at least one of high molecular weight chitosan, low molecular weight chitosan and water-soluble chitosan.
Description
Technical Field
The invention relates to the field of biological medicine, in particular to a preparation method of a phospholipid chitosan medicine.
Background
With the continuous development of biotechnology, protein polypeptide drugs are increasingly widely used. Protein polypeptide drugs are mainly administered by injection, and long-term frequent injection causes great discomfort and pain to patients, so that non-injection administration of protein polypeptide drugs is always widely concerned. Among them, the oral administration of protein and peptide drugs is a hot research on the administration of protein and peptide drugs. Aiming at the main problems of oral administration, such as short half-life period, poor gastrointestinal stability, difficulty in passing through gastrointestinal mucosa and the like, novel drug carriers such as liposome, nano-particles, emulsion, microspheres and the like are continuously emerged to realize the purpose of oral delivery of protein polypeptide drugs, wherein the liposome and the nano-particles are common drug oral delivery means.
The liposome has the characteristics of good biocompatibility, biodegradability, nontoxicity and the like, and can carry substances such as medicines, nutrient substances, functional factors and the like. Researches show that the liposome can effectively improve the bioavailability of the medicament and the functional factors, enhance the stability of the medicament and the functional factors, prolong the circulation time in vivo, realize the slow release and the like. However, the liposome structure is unstable, and has the problems of heat sensitivity, large particle size in the storage process, aggregation, core material leakage and the like, and the biodegradable chitosan nanoparticles are widely used as delivery carriers of biological medicines because of non-toxicity, wide sources, good biocompatibility and biodegradability. Research shows that the chitosan surface is charged with a large amount of positive charges, the chitosan can be adsorbed to the mucosal surface and can rapidly open the tight connection between epithelial cells, and the chitosan serving as a carrier material is coated with nanoparticles prepared from protein polypeptide drugs, so that transmembrane transport and drug absorption of the drugs can be promoted, and the bioavailability is remarkably improved.
Therefore, a preparation method of phospholipid chitosan medicine is provided to solve the problems.
Disclosure of Invention
The invention aims to provide a preparation method of a phospholipid chitosan medicine, which aims to solve the problems in the background technology.
In order to achieve the purpose, the invention provides the following technical scheme: a phospholipid chitosan medicine is composed of the following components in parts by weight: 1-10 parts of protein polypeptide drugs, 10-100 parts of phospholipid and 1-10 parts of chitosan, wherein the phospholipid material is at least one selected from natural phospholipid and synthetic phospholipid, and the chitosan is at least one selected from high molecular weight chitosan, low molecular weight chitosan and water-soluble chitosan.
A preparation method of a phospholipid chitosan medicine comprises the following steps:
dissolving a protein polypeptide drug in absolute ethyl alcohol to obtain a protein polypeptide drug solution, and dissolving phospholipid in absolute ethyl alcohol to obtain a phospholipid solution;
slowly adding the protein polypeptide drug solution into the phospholipid solution, stirring at 35-55 ℃ for 40min to convert the solvent into volatile solvent, and drying to obtain protein polypeptide drug phospholipid complex powder;
step three, taking chitosan, adding the chitosan into a glacial acetic acid aqueous solution, and magnetically stirring to obtain a chitosan solution;
and step four, rapidly adding the protein polypeptide drug phospholipid complex powder into a chitosan solution under magnetic stirring, rotationally evaporating to remove the organic solvent, and finally adding a protective agent to prepare freeze-dried powder through freeze drying.
A preparation device of phospholipid chitosan medicine comprises a preparation platform, wherein a first L frame plate and a second L frame plate are fixed at the top end of the preparation platform, a controller is fixed at the center of the side face of the vertical part of the first L frame plate, and the controller comprises a display screen and a control key;
a medicine solution preparation assembly is arranged on the side face of the first L frame plate and comprises a medicine dissolving cylinder, a first solvent pipe, a first scale, a medicine inlet pipe, a first liquid outlet pipe, a first electromagnetic valve, a first stirring gear, a first rotating rod, a first stirring rod, a first through hole, a first support plate, a first round hole, a first motor and a first driving gear;
the first solvent tube is communicated with the center of the top end of the medicine dissolving cylinder, the first scale is arranged at the center of the side wall of the medicine dissolving cylinder, the drug inlet pipe is a hose, the end part of the drug inlet pipe is communicated with the side wall of the drug dissolving cylinder in a penetrating way, the first liquid outlet pipe is communicated with the center of the bottom end of the drug dissolving cylinder in a penetrating way, the first electromagnetic valve is arranged in the first liquid outlet pipe, the first stirring gear is arranged in the medicine dissolving cylinder, the first rotating rod is fixed at the center of the bottom end of the first stirring gear, the first stirring rod is arranged on the side wall of the first rotating rod, the first through hole is arranged on the side wall of the drug dissolving cylinder, the first supporting plate is fixed on the side surface of the first L-shaped frame plate, the first round hole is arranged on the first support plate, the medicine dissolving cylinder passes through the first round hole, the first motor is screwed at the top end of the first support plate, the first driving gear is arranged at the end part of the first motor output shaft and penetrates through the first round hole to be meshed with the first stirring gear;
a phospholipid solution preparation assembly is arranged on the side surface of the second L-shaped frame plate and comprises a phospholipid dissolving cylinder, a second solvent pipe, a volatilization pipe, a second scale, a phospholipid inlet pipe, a second liquid outlet pipe, a second electromagnetic valve, a second stirring gear, a second rotating rod, a second stirring rod, a second through hole, a second support plate, a second round hole, a second motor and a second driving gear;
the second solvent tube is communicated with the top end center of the phospholipid dissolving cylinder, the volatilization tube is communicated with the top end of the phospholipid dissolving cylinder, the second scale is arranged at the center of the side wall of the phospholipid dissolving cylinder, the phospholipid inlet tube is a hose, the end part of the phospholipid inlet tube is communicated with the side wall of the phospholipid dissolving cylinder in a penetrating manner, the second liquid outlet tube is communicated with the center of the bottom end of the phospholipid dissolving cylinder in a penetrating manner, the second electromagnetic valve is arranged in the second liquid outlet tube, the second stirring gear is arranged in the phospholipid dissolving cylinder, the second rotating rod is fixed at the bottom center of the second stirring gear, the second stirring rod is arranged on the side wall of the second rotating rod, the second through hole is arranged on the side wall of the phospholipid dissolving cylinder, the second support plate is fixed on the side surface of the second L support plate, the second round hole is arranged on the second support plate, the phospholipid dissolving cylinder passes through the second round hole, the second motor, the second driving gear is arranged at the end part of the output shaft of the second motor and penetrates through the second round hole to be meshed with the second stirring gear;
a drain pipe bottom is connected with the fluid-discharge tube No. one, No. one the drain pipe runs through No. two L frame plates and a phospholipid dissolution section of thick bamboo intercommunication sets up and the intercommunication position is provided with the check valve No. one, preparation bench top is provided with a chitosan dissolution section of thick bamboo, the exit tube has been seted up to chitosan dissolution section of thick bamboo side, No. two drain pipe bottom is connected with the fluid-discharge tube No. two, No. two drain pipes and chitosan dissolution section of thick bamboo intercommunication set up and the intercommunication position is provided with the check valve No. two.
Furthermore, the height of the second L frame plate is smaller than that of the first L frame plate, the bottom ends of the side walls of the vertical parts of the first L frame plate and the second L frame plate are symmetrically fixed with positioning plates, the positioning plates are in threaded connection with positioning bolts, and the positioning bolts are in threaded connection with the positioning plates and the preparation platform.
Furthermore, the first L frame plate vertical part side and the horizontal part bottom end are in threaded connection with a first support inclined plate, and the second L frame plate vertical part side and the horizontal part bottom end are in threaded connection with a second support inclined plate.
Furthermore, the medicine inlet pipe is arranged close to the top end of the inner cavity of the medicine dissolving cylinder, the horizontal plane of the bottom end of the first stirring gear is higher than the horizontal plane of the bottom end of the side wall of the medicine inlet pipe communicated with the medicine dissolving cylinder, the diameter of the first stirring gear is smaller than the inner diameter of the medicine dissolving cylinder, and the uppermost stirring rod is arranged lower than the side wall of the medicine inlet pipe communicated with the medicine dissolving cylinder.
Furthermore, the phospholipid inlet pipe is arranged close to the top end of the inner cavity of the phospholipid dissolving cylinder, the horizontal plane of the bottom end of the second stirring gear is higher than the horizontal plane of the bottom end of the side wall of the phospholipid dissolving cylinder communicated with the phospholipid inlet pipe, the diameter of the second stirring gear is smaller than the inner diameter of the phospholipid dissolving cylinder, the uppermost stirring rod is arranged lower than the side wall of the phospholipid dissolving cylinder communicated with the phospholipid inlet pipe, and the diameter of the second driving gear is smaller than the diameter of the second stirring gear.
Furthermore, the position of the first liquid discharge pipe communicated with the phospholipid dissolving cylinder is lower than the bottom end of the first support plate, and the position of the second liquid discharge pipe communicated with the chitosan dissolving cylinder is higher than the center of the chitosan dissolving cylinder.
Furthermore, a solvent pipe and No. two solvent pipes are respectively the activity run through No. one L frame plate and No. two L frame plate top setting, a solvent pipe and No. two solvent pipe lateral walls all are provided with connecting thread and threaded connection has the go-between, the spiro union has connecting screw between go-between and No. two L frame plate tops.
Furthermore, one side of the chitosan dissolving cylinder is provided with a vertical rod, and a magnetic stirrer and a magnetic stirring rod are arranged on the vertical rod.
The invention has the beneficial effects that:
1. the invention conveys the medicine by combining the phospholipid and the chitosan, utilizes the liposome to have good biocompatibility, biodegradability and nontoxicity, combines the chitosan surface with a large amount of positive charges, can be adsorbed to the mucosal surface and quickly open the tight connection between epithelial cells, solves the problems that protein polypeptide medicine carries less negative charges and can not directly form stable nanoparticles or other preparations with the chitosan under the action of charge attraction, has medicine leakage and unstable liposome structure, is sensitive to heat, has large grain diameter, aggregation and core material leakage in the storage process, has strong medicine carrying capacity, is simple in preparation method, and is beneficial to large-scale production of enterprises;
2. according to the invention, the medicine solution preparation assembly and the phospholipid solution preparation assembly are arranged, the medicine solution preparation assembly is utilized to dissolve protein polypeptide medicines in absolute ethyl alcohol, during preparation, the first motor drives the first driving gear to rotate, the first stirring gear is in meshing transmission to rotate, so that the first stirring rod rotates to stir and dissolve the protein polypeptide medicines, the phospholipid solution preparation assembly is utilized to dissolve phospholipid in absolute ethyl alcohol, during preparation, the second motor drives the second driving gear to rotate, the second stirring gear is in meshing transmission to rotate, so that the second stirring rod rotates to stir and dissolve the phospholipid, and the dissolving efficiency is improved in a stirring and mixing mode;
3. according to the invention, the first liquid discharge pipe, the first check valve, the chitosan dissolving cylinder, the outlet pipe, the second liquid discharge pipe, the second check valve, the vertical rod, the magnetic stirrer, the magnetic stirring rod, the connecting thread, the connecting ring and the connecting screw are arranged, the first liquid discharge pipe and the first check valve are used for adding a medicine solution into a phospholipid solution, the second liquid discharge pipe and the second check valve are used for adding a mixed medicine solution and a phospholipid solution into the chitosan solution, the mixed protein polypeptide medicine and phospholipid compound powder is conveniently added into the chitosan solution under the action of the magnetic stirrer and the magnetic stirring rod, so that the three are uniformly mixed, and the threads, the connecting ring and the connecting screw are simultaneously connected, so that the medicine dissolving cylinder and the phospholipid dissolving cylinder are conveniently disassembled and assembled.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a flow chart of a preparation method of the present invention;
FIG. 2 is a schematic structural view of the present invention;
FIG. 3 is a schematic cross-sectional view of the present invention;
FIG. 4 is a side view of the structure of the present invention;
FIG. 5 is a schematic view of a chitosan dissolving cartridge according to the present invention;
FIG. 6 is an enlarged view of part A of the present invention;
FIG. 7 is an enlarged view of the portion B of the present invention;
FIG. 8 is a schematic view of a drug solution preparation assembly of the present invention;
FIG. 9 is a schematic view of a phospholipid solution preparation module according to the present invention;
FIG. 10 is an enlarged view of the portion C of the present invention;
FIG. 11 is an enlarged view of the D-section of the present invention;
in the drawings, the components represented by the respective reference numerals are listed below:
1. preparation platform 2, first L frame plate 3, second L frame plate 4, positioning plate 5, positioning bolt 6, controller 7, first supporting inclined plate 8, second supporting inclined plate 9, drug dissolving cylinder 10, first solvent tube 11, first scale 12, drug inlet tube 13, first outlet tube 14, first electromagnetic valve 15, first stirring gear 16, first rotating rod 17, first stirring rod 18, first through opening 19, first supporting plate 20, first round hole 21, first motor 22, first driving gear 23, phospholipid dissolving cylinder 230, phospholipid inlet tube 231, second through opening 24, second solvent tube 25, volatilization tube 26, second scale 27, second outlet tube 28, second electromagnetic valve 29, second stirring gear 30, second rotating rod 31, second stirring rod 32, second supporting plate 33, second round hole 34, second motor 35, second driving gear 36, first discharging tube 37, first one-way valve 38, second dissolving cylinder 39, second stirring tube 40, second discharging tube 42, and one-way vertical discharging valve 42 The rod 43, the magnetic stirrer 44, the magnetic stirring rod 45, the connecting thread 46, the connecting ring 47 and the connecting screw.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The present invention will be further described with reference to the following examples.
Example 1
As shown in figure 1, the phospholipid chitosan medicine consists of the following components in parts by weight: 1-10 parts of protein polypeptide drugs, 10-100 parts of phospholipid and 1-10 parts of chitosan, wherein the phospholipid material is at least one selected from natural phospholipid and synthetic phospholipid, and the chitosan is at least one selected from high molecular weight chitosan, low molecular weight chitosan and water-soluble chitosan.
A preparation method of a phospholipid chitosan medicine comprises the following steps:
dissolving a protein polypeptide drug in absolute ethyl alcohol to obtain a protein polypeptide drug solution, and dissolving phospholipid in absolute ethyl alcohol to obtain a phospholipid solution;
slowly adding the protein polypeptide drug solution into the phospholipid solution, stirring at 35-55 ℃ for 40min to convert the solvent into volatile solvent, and drying to obtain protein polypeptide drug phospholipid complex powder;
step three, taking chitosan, adding the chitosan into a glacial acetic acid aqueous solution, and magnetically stirring to obtain a chitosan solution;
rapidly adding the protein polypeptide drug phospholipid complex powder into a chitosan solution under magnetic stirring, rotationally evaporating to remove the organic solvent, and finally adding a protective agent to prepare freeze-dried powder through freeze drying;
the phospholipid and the chitosan are combined to convey the medicament, the liposome has good biocompatibility, biodegradability and nontoxicity, a large amount of positive charges are charged on the surface of the chitosan, the chitosan can be adsorbed to the surface of a mucous membrane and the tight connection between epithelial cells is rapidly opened, the problems that protein polypeptide medicaments carry fewer negative charges and cannot directly form stable nanoparticles or other preparations with the chitosan under the action of charge attraction force, medicament leakage and unstable liposome structure exist, heat sensitivity exists, the particle size is increased, aggregation and core material leakage in the storage process are solved, the medicament carrying capacity is strong, the preparation method is simple, and the large-scale production of enterprises is facilitated.
Example 2
Example 2 is a further modification to example 1.
As shown in fig. 2, 3, 4, 5, 6, 7, 8 and 9, the preparation device for phospholipid chitosan medicine comprises a preparation table 1, wherein a first L frame plate 2 and a second L frame plate 3 are fixed at the top end of the preparation table 1, a controller 6 is fixed at the center of the side surface of the vertical part of the first L frame plate 2, the controller 6 comprises a display screen and a control key, the height of the second L frame plate 3 is smaller than that of the first L frame plate 2, a positioning plate 4 is symmetrically fixed at the bottom end of the side wall of the vertical part of the first L frame plate 2 and the second L frame plate 3, the positioning plate 4 is in threaded connection with a positioning bolt 5, the positioning bolt 5 is in threaded connection with the positioning plate 4 and the preparation table 1, so as to facilitate the installation and the disassembly of the first L frame plate 2 and the second L frame plate 3, a first support inclined plate 7 is in threaded connection with the side surface of the vertical part and the bottom end of the horizontal part of the first L frame plate 2, a second support inclined plate 8 is in, the arrangement of the first supporting inclined plate 7 and the second supporting inclined plate 8 strengthens the stability of the first L frame plate 2 and the second L frame plate 3;
the side surface of the first L frame plate 2 is provided with a medicine solution preparation assembly, the medicine solution preparation assembly comprises a medicine dissolving barrel 9, a first solvent pipe 10, a first scale 11, a medicine inlet pipe 12, a first liquid outlet pipe 13, a first electromagnetic valve 14, a first stirring gear 15, a first rotating rod 16, a first stirring rod 17, a first through port 18, a first supporting plate 19, a first round hole 20, a first motor 21 and a first driving gear 22, the first solvent pipe 10 is communicated with the top end center of the medicine dissolving barrel 9, the first scale 11 is arranged at the side wall center of the medicine dissolving barrel 9, the medicine inlet pipe 12 is a hose, the end part of the medicine inlet pipe is communicated with the side wall of the medicine dissolving barrel 9 in a penetrating manner, the first liquid outlet pipe 13 is communicated with the bottom end center of the medicine dissolving barrel 9 in a penetrating manner, the first electromagnetic valve 14 is arranged in the first liquid outlet pipe 13, the first stirring gear 15 is arranged in the medicine dissolving barrel 9, the first rotating rod 16 is fixed at the bottom end center, the first stirring rod 17 is arranged on the side wall of the first rotating rod 16, the first through hole 18 is formed in the side wall of the medicine dissolving cylinder 9, the first supporting plate 19 is fixed on the side face of the first L-shaped frame plate 2, the first round hole 20 is formed in the first supporting plate 19, the medicine dissolving cylinder 9 penetrates through the first round hole 20, the first motor 21 is in threaded connection with the top end of the first supporting plate 19, and the first driving gear 22 is installed at the end part of an output shaft of the first motor 21 and penetrates through the first round hole 20 to be meshed with the first stirring gear 15; the preparation method comprises the following steps of (1) dissolving the protein polypeptide medicine in absolute ethyl alcohol by utilizing a medicine solution preparation assembly, wherein during preparation, a first motor 21 drives a first driving gear 22 to rotate, and a first stirring gear 15 is in meshing transmission to rotate, so that a first stirring rod 17 rotates to stir and dissolve the protein polypeptide medicine;
a phospholipid solution preparation assembly is arranged on the side surface of the second L-shaped frame plate 3, the phospholipid solution preparation assembly comprises a phospholipid dissolving cylinder 23, a second solvent pipe 24, a volatilization pipe 25, a second scale 26, a phospholipid inlet pipe 230, a second liquid outlet pipe 27, a second electromagnetic valve 28, a second stirring gear 29, a second rotating rod 30, a second stirring rod 31, a second through hole 231, a second supporting plate 32, a second round hole 33, a second motor 34 and a second driving gear 35, the second solvent pipe 24 is communicated with the center of the top end of the phospholipid dissolving cylinder 23, the volatilization pipe 26 is communicated with the top end of the phospholipid dissolving cylinder 23, the second scale 26 is arranged at the center of the side wall of the phospholipid dissolving cylinder 23, the phospholipid inlet pipe 230 is a hose, the end part of the phospholipid inlet pipe penetrates through the side wall of the phospholipid dissolving cylinder 23, the second liquid outlet pipe 27 penetrates through the center of the bottom end of the phospholipid dissolving cylinder 23, the second electromagnetic valve 28 is arranged in the second liquid outlet pipe 27, the second stirring gear 29 is, a second rotating rod 30 is fixed at the center of the bottom end of a second stirring gear 29, a second stirring rod 31 is arranged on the side wall of the second rotating rod 30, a second through hole 231 is formed in the side wall of a phospholipid dissolving cylinder 23, a second supporting plate 32 is fixed on the side surface of a second L-shaped frame plate 3, a second round hole 33 is formed in the second supporting plate 32, the phospholipid dissolving cylinder 23 penetrates through the second round hole 33, a second motor 34 is in threaded connection with the top end of the second supporting plate 32, and a second driving gear 35 is installed at the end part of an output shaft of the second motor 34 and penetrates through the second round hole 33 to be meshed with the second stirring gear 29; the phospholipid solution preparation component is used for dissolving phospholipid in absolute ethyl alcohol, and during preparation, a second motor 34 drives a second driving gear 35 to rotate and drives a second stirring gear 29 to rotate in a meshing manner, so that a second stirring rod 31 rotates to stir and dissolve the phospholipid;
no. one drain pipe 13 bottom is connected with fluid-discharge tube 36, No. one drain pipe 36 runs through No. two L frame boards 3 and a phospholipid dissolving section of thick bamboo 23 intercommunication setting and the intercommunication position is provided with check valve 37, preparation platform 1 top is provided with a chitosan dissolving section of thick bamboo 38, exit tube 39 has been seted up to a chitosan dissolving section of thick bamboo 38 side, No. two drain pipe 27 bottoms are connected with No. two drain pipes 40, No. two drain pipes 40 and a chitosan dissolving section of thick bamboo 38 intercommunication setting and intercommunication position are provided with No. two check valve 41, utilize No. one drain pipe 36 and No. one check valve 37 to realize the interpolation of drug solution to phospholipid solution, utilize No. two drain pipes 40 and No. two check valve 41 to realize that drug solution and phospholipid solution after the mixture add in the chitosan solution.
Example 3
Example 3 is a further modification to example 1.
As shown in fig. 6, 7, 10 and 11, the medicine inlet tube 12 is arranged near the top end of the inner cavity of the medicine dissolving tube 9, the horizontal plane of the bottom end of the first stirring gear 15 is higher than the horizontal plane of the bottom end of the position where the medicine inlet tube 12 is communicated with the side wall of the medicine dissolving tube 9, the diameter of the first stirring gear 15 is smaller than the inner diameter of the medicine dissolving tube 9, the uppermost first stirring rod 17 is arranged lower than the position where the medicine inlet tube 12 is communicated with the side wall of the medicine dissolving tube 9, the phospholipid inlet tube 230 is arranged near the top end of the inner cavity of the phospholipid dissolving tube 23, the horizontal plane of the bottom end of the second stirring gear 29 is higher than the horizontal plane of the bottom end of the position where the phospholipid inlet tube 230 is communicated with the side wall of the phospholipid dissolving tube 23, the diameter of the second stirring gear 29 is smaller than the inner diameter of the phospholipid dissolving tube 23, the uppermost second stirring rod 31 is arranged lower than the position where the phospholipid, the position of first fluid-discharge tube 36 and a phospholipid dissolving cylinder 23 intercommunication is less than the bottom of first backup pad 19, the position of second fluid-discharge tube 40 and a chitosan dissolving cylinder 38 intercommunication pair is higher than the chitosan dissolving cylinder 38 center, chitosan dissolving cylinder 38 one side is provided with pole 42, be provided with magnetic stirrer 43 and magnetic stirring pole 44 on the pole 42, first solvent pipe 10 and second solvent pipe 24 respectively the activity run through the setting of first L frame board 2 and second L frame board 3 top, first solvent pipe 10 and second solvent pipe 24 lateral wall all are provided with connecting thread 45 and threaded connection has a go-between 46, the spiro union has connecting screw 47 between go-between 46 and L frame board 2 and second L frame board 3 top.
When in use, the drug solution preparation component is utilized to dissolve protein polypeptide drugs in absolute ethyl alcohol, when in preparation, the first motor 21 drives the first driving gear 22 to rotate, the first stirring gear 15 is in meshing transmission to rotate, so that the first stirring rod 17 rotates to stir and dissolve the protein polypeptide drugs, the phospholipid solution preparation component is utilized to dissolve phospholipid in absolute ethyl alcohol, when in preparation, the second motor 34 drives the second driving gear 35 to rotate, the second stirring gear 29 is in meshing transmission to rotate, so that the second stirring rod 31 rotates to stir and dissolve phospholipid, chitosan is taken and put into a chitosan dissolving cylinder 38 with glacial acetic acid aqueous solution, after magnetic stirring, chitosan solution is obtained, then the first liquid discharge pipe 36 and the first one-way valve 37 are utilized to realize the addition of the drug solution into the phospholipid solution, and the second motor 34 drives the second driving gear 35 to rotate in the process, the second stirring gear 29 is in meshing transmission to rotate, so that the second stirring rod 31 rotates, the auxiliary medicine solution is added into the phospholipid solution, protein polypeptide medicine phospholipid compound powder is obtained after rotation, volatilization and drying, then the mixed medicine solution and phospholipid solution are added into the chitosan solution by utilizing the second liquid discharge pipe 40 and the second one-way valve 41, the mixed protein polypeptide medicine phospholipid compound powder is conveniently added into the chitosan solution under the action of the magnetic stirrer 43 and the magnetic stirring rod 44, the three are uniformly mixed, organic solvent is removed by rotary evaporation, and finally, a protective agent is added, and freeze-drying is carried out to prepare freeze-dried medicine powder.
In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The preferred embodiments of the invention disclosed above are intended to be illustrative only. The preferred embodiments are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Obviously, many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and the practical application, to thereby enable others skilled in the art to best utilize the invention. The invention is limited only by the claims and their full scope and equivalents.
Claims (10)
1. A phospholipid chitosan drug, which is characterized in that: the phospholipid chitosan medicine comprises the following components in parts by weight: 1-10 parts of protein polypeptide drugs, 10-100 parts of phospholipid and 1-10 parts of chitosan, wherein the phospholipid material is at least one selected from natural phospholipid and synthetic phospholipid, and the chitosan is at least one selected from high molecular weight chitosan, low molecular weight chitosan and water-soluble chitosan.
2. The method for preparing a phospholipid chitosan drug according to claim 1, wherein the method comprises the following steps: the preparation process comprises the following steps:
dissolving a protein polypeptide drug in absolute ethyl alcohol to obtain a protein polypeptide drug solution, and dissolving phospholipid in absolute ethyl alcohol to obtain a phospholipid solution;
slowly adding the protein polypeptide drug solution into the phospholipid solution, stirring at 35-55 ℃ for 40min to convert the solvent into volatile solvent, and drying to obtain protein polypeptide drug phospholipid complex powder;
step three, taking chitosan, adding the chitosan into a glacial acetic acid aqueous solution, and magnetically stirring to obtain a chitosan solution;
and step four, rapidly adding the protein polypeptide drug phospholipid complex powder into a chitosan solution under magnetic stirring, rotationally evaporating to remove the organic solvent, and finally adding a protective agent to prepare freeze-dried powder through freeze drying.
3. The preparation device of phospholipid chitosan drug according to claim 1, comprising a preparation platform (1), characterized in that: a first L frame plate (2) and a second L frame plate (3) are fixed at the top end of the preparation table (1), a controller (6) is fixed at the center of the side face of the vertical part of the first L frame plate (2), and the controller (6) comprises a display screen and a control key;
a drug solution preparation assembly is arranged on the side surface of the first L-shaped frame plate (2), and comprises a drug dissolving cylinder (9), a first solvent tube (10), a first scale (11), a drug inlet tube (12), a first liquid outlet tube (13), a first electromagnetic valve (14), a first stirring gear (15), a first rotating rod (16), a first stirring rod (17), a first through opening (18), a first support plate (19), a first round hole (20), a first motor (21) and a first driving gear (22);
the utility model discloses a medicine dissolving section of thick bamboo (9) top center is dissolved to a medicine to solvent pipe (10) intercommunication, scale (11) set up and dissolve a section of thick bamboo (9) lateral wall center at the medicine, the medicine advances pipe (12) and runs through the intercommunication on medicine dissolving section of thick bamboo (9) lateral wall for hose and tip, drain pipe (13) run through intercommunication medicine dissolving section of thick bamboo (9) bottom center and set up, solenoid valve (14) set up in drain pipe (13) No. one, install in medicine dissolving section of thick bamboo (9) a stirring gear (15), bull stick (16) are fixed at a stirring gear (15) bottom center, a stirring rod (17) set up on bull stick (16) lateral wall, a logical mouth (18) is seted up and is dissolved a section of thick bamboo (9) lateral wall at the medicine, a backup pad (19) are fixed in L frame plate (2) side No. one, a round hole (20) are seted up on backup pad (19), the drug dissolving cylinder (9) penetrates through the first round hole (20), the first motor (21) is screwed at the top end of the first supporting plate (19), and the first driving gear (22) is installed at the end part of an output shaft of the first motor (21) and penetrates through the first round hole (20) to be meshed with the first stirring gear (15);
a phospholipid solution preparation assembly is arranged on the side surface of the second L-shaped frame plate (3), and comprises a phospholipid dissolving cylinder (23), a second solvent pipe (24), a volatilization pipe (25), a second scale (26), a phospholipid inlet pipe (230), a second liquid outlet pipe (27), a second electromagnetic valve (28), a second stirring gear (29), a second rotating rod (30), a second stirring rod (31), a second through hole (231), a second support plate (32), a second round hole (33), a second motor (34) and a second driving gear (35);
the utility model discloses a phospholipid dissolving tank, including No. two solvent pipes (24), volatile pipe (26), phospholipid dissolving tank (23), No. two scales (26), No. two solvent pipes (24) intercommunication are at phospholipid dissolving tank (23) top center, volatile pipe (26) intercommunication is on phospholipid dissolving tank (23) top, No. two scales (26) set up at phospholipid dissolving tank (23) lateral wall center, phospholipid advances pipe (230) and runs through the intercommunication on phospholipid dissolving tank (23) lateral wall for hose and tip, No. two drain pipes (27) run through intercommunication phospholipid dissolving tank (23) bottom center and set up, No. two solenoid valves (28) set up in No. two drain pipes (27), No. two stirring gear (29) are installed in phospholipid dissolving tank (23), No. two bull stick (30) are fixed at No. two stirring gear (29) bottom center, No. two stirring rod (31) set up on No. two bull stick (30) lateral wall, No. two opening (231) are seted up at phospholipid dissolving tank (23) lateral wall, No. two backup pad (32) are fixed in No. two L, the second round hole (33) is formed in the second supporting plate (32), the phospholipid dissolving cylinder (23) penetrates through the second round hole (33), the second motor (34) is connected to the top end of the second supporting plate (32) in a threaded mode, and the second driving gear (35) is installed at the end portion of an output shaft of the second motor (34) and penetrates through the second round hole (33) to be meshed with the second stirring gear (29);
no. one drain pipe (13) bottom is connected with fluid-discharge tube (36), No. one drain pipe (36) run through No. two L frame boards (3) and a phosphatide dissolves a section of thick bamboo (23) intercommunication setting and intercommunication position and is provided with check valve (37), preparation platform (1) top is provided with a chitosan and dissolves a section of thick bamboo (38), exit tube (39) have been seted up to chitosan and dissolve a section of thick bamboo (38) side, No. two drain pipe (27) bottom is connected with No. two fluid-discharge tube (40), No. two fluid-discharge tube (40) and chitosan dissolve a section of thick bamboo (38) intercommunication setting and intercommunication position and be provided with No. two check valve (41).
4. The apparatus for preparing phospholipid chitosan drug according to claim 3, wherein: the height of No. two L frame plates (3) is less than the height of No. one L frame plate (2), No. one L frame plate (2) and No. two L frame plates (3) vertical part side wall bottom end symmetry are fixed with locating plate (4), locating plate (4) threaded connection has positioning bolt (5), positioning bolt (5) threaded connection locating plate (4) and preparation platform (1).
5. The apparatus for preparing phospholipid chitosan drug according to claim 3, wherein: no. one L frame plate (2) vertical portion side and horizontal part bottom spiro union have support swash plate (7) No. one, No. two L frame plate (3) vertical portion side and horizontal part bottom spiro union have support swash plate (8) No. two.
6. The apparatus for preparing phospholipid chitosan drug according to claim 3, wherein: the medicine advances pipe (12) and is close to medicine dissolving cylinder (9) inner chamber top setting, the horizontal plane that a stirring gear (15) bottom is located is higher than the medicine and advances pipe (12) intercommunication medicine dissolving cylinder (9) lateral wall position bottom horizontal plane that locates, the diameter of a stirring gear (15) is less than the internal diameter that medicine dissolved cylinder (9), the top stirring rod (17) are less than medicine and advance pipe (12) intercommunication medicine dissolving cylinder (9) lateral wall position and set up.
7. The apparatus for preparing phospholipid chitosan drug according to claim 3, wherein: the phospholipid inlet pipe (230) is arranged close to the top end of an inner cavity of the phospholipid dissolving cylinder (23), the horizontal plane at the bottom end of the second stirring gear (29) is higher than the horizontal plane at the bottom end of the side wall of the phospholipid dissolving cylinder (23) communicated with the phospholipid inlet pipe (230), the diameter of the second stirring gear (29) is smaller than the inner diameter of the phospholipid dissolving cylinder (23), the uppermost stirring rod (31) is arranged lower than the side wall of the phospholipid inlet pipe (230) communicated with the phospholipid dissolving cylinder (23), and the diameter of the second driving gear (35) is smaller than the diameter of the second stirring gear (29).
8. The apparatus for preparing phospholipid chitosan drug according to claim 3, wherein: the position of the first liquid discharge pipe (36) communicated with the phospholipid dissolving cylinder (23) is lower than the bottom end of the first support plate (19), and the position of the communicated pair of the second liquid discharge pipe (40) and the chitosan dissolving cylinder (38) is higher than the center of the chitosan dissolving cylinder (38).
9. The apparatus for preparing phospholipid chitosan drug according to claim 3, wherein: solvent pipe (10) and No. two solvent pipe (24) are moved through L frame plate (2) and No. two L frame plate (3) top respectively and are set up, solvent pipe (10) and No. two solvent pipe (24) lateral wall all are provided with connecting thread (45) and threaded connection has go-between (46), spiro union has connecting screw (47) between go-between (46) and No. L frame plate (2) and No. two L frame plate (3) tops.
10. The apparatus for preparing phospholipid chitosan drug according to claim 3, wherein: a vertical rod (42) is arranged on one side of the chitosan dissolving cylinder (38), and a magnetic stirrer (43) and a magnetic stirring rod (44) are arranged on the vertical rod (42).
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| CN202110058959.0A CN112716906A (en) | 2021-01-17 | 2021-01-17 | Preparation method of phospholipid chitosan medicine |
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| CN105617362A (en) * | 2014-10-27 | 2016-06-01 | 中国医学科学院药物研究所 | Novel insulin-phospholipid-chitosan self-assembled microparticle carrier and preparation thereof |
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