CN117338696A - Anhydrous matrix gel containing chitosan and its preparation method and use - Google Patents
Anhydrous matrix gel containing chitosan and its preparation method and use Download PDFInfo
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- CN117338696A CN117338696A CN202311304949.6A CN202311304949A CN117338696A CN 117338696 A CN117338696 A CN 117338696A CN 202311304949 A CN202311304949 A CN 202311304949A CN 117338696 A CN117338696 A CN 117338696A
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- chitosan
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- polyethylene glycol
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- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 34
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- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 25
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 24
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- 238000003756 stirring Methods 0.000 claims description 41
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
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- 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
- A61K47/02—Inorganic compounds
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
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- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Epidemiology (AREA)
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- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a chitosan-containing anhydrous matrix gel, and a preparation method and application thereof. The provided anhydrous matrix gel containing chitosan comprises the following components in parts by weight: 5-15 parts of chitosan, 0.5-3 parts of carbomer, 30-50 parts of polyethylene glycol, 20-30 parts of transdermal enhancer, 20-40 parts of humectant, 5-15 parts of polyvinylpyrrolidone and 0.5-2 parts of pH regulator. The anhydrous matrix gel is prepared by dispersing carbomer in polyethylene glycol to fully swell, respectively adding transdermal enhancer, humectant and polyvinylpyrrolidone to uniformity, dripping pH regulator, and adding chitosan. The provided anhydrous matrix gel realizes high loading of insoluble medicine chitosan, and plays roles of stopping bleeding, easing pain, relieving edema and promoting healing. And the texture is uniform and fine, and the wound surface can absorb the seepage of the wound surface and can be permanently adhered to and isolated from the wound surface when the wound surface swells in water, so that the protection effect is realized.
Description
Technical Field
The invention relates to the field of medicines, in particular to an anhydrous matrix gel containing chitosan, a preparation method and application thereof.
Background
According to the related general investigation data, the incidence rate of anorectal diseases is 59.1 percent, which is far higher than that of common diseases such as cardiovascular and cerebrovascular diseases, hypertension and the like, and the incidence rate of hemorrhoids in all anorectal diseases is up to 87.2 percent. Along with the change of the work and the rest of people and the common influence of genetic factors, environmental factors and the like, the incidence rate of hemorrhoids is continuously increased. Hemorrhoids can be developed at any age, the developed crowd is relatively wide, and the daily life of patients is seriously affected after the development, so that the life quality is reduced. In clinic, the methods for treating hemorrhoids include life improvement treatment, drug treatment and surgical treatment. Patients with mild symptoms usually take the corresponding drugs locally, orally or by injection, however, the patients with poor therapeutic effect and severe hemorrhoids need to be treated by surgery. Wound fluid leakage, anal pain and oedema are common postoperative complications of hemorrhoids. The wound position after operation has more exudates, and the local tissue edema can cause microcirculation disturbance, so that ischemic neuralgia appears at the operation position, and the pain can stimulate sphincter spasm and contraction in anus, thereby preventing local blood circulation and lymphatic fluid from flowing back, causing edema to aggravate and forming malignant circulation. Therefore, effective postoperative care has important significance for promoting wound healing and relieving pain of patients.
The gel can be used as an external preparation to directly exert efficacy on an action part, avoid adverse reaction caused by gastrointestinal tract absorption, is easy to smear, has mechanical properties similar to those of physiological soft tissues, and has been widely used for postoperative care of hemorrhoids based on the advantages of convenient use, good viscosity and small irritation. Chitosan is a natural high molecular polymer and is the only basic polysaccharide with cationic charge discovered so far. Research shows that chitosan has good hemostatic effect and can shorten the time for wound healing by promoting proliferation and migration of fibroblasts. In addition, the strong tissue adhesion of chitosan can protect the wound surface from the severe rectal environment, and has the effects of relieving the pain of the wound surface and promoting the absorption of local edema.
At present, chitosan gel is used as a post-hemorrhoid nursing product in the market, but the water-containing matrix weakens the management capability of wound seepage to a certain extent, and the compatibility caused by the poor solubility of chitosan and the cationic property of chitosan is poor, so that the chitosan content in the existing product is low, the effect of chitosan cannot be fully exerted, the process for modifying chitosan is complex, the controllability is poor, the production cost is increased, and the practicability to factories is low.
Disclosure of Invention
The invention aims at overcoming the defects and shortcomings of the prior art and provides an anhydrous matrix gel containing chitosan, and a preparation method and application thereof. The provided anhydrous matrix gel can realize high chitosan loading, so that the effects of stopping bleeding, relieving pain, relieving edema and promoting healing can be exerted.
In order to achieve the above object, the present invention provides an anhydrous matrix gel containing chitosan, comprising, in parts by weight: 5-15 parts of chitosan, 0.5-3 parts of carbomer, 30-50 parts of polyethylene glycol, 20-30 parts of transdermal enhancer, 20-40 parts of humectant, 5-15 parts of polyvinylpyrrolidone and 0.5-2 parts of pH regulator.
The anhydrous matrix gel containing chitosan provided by the invention does not contain water. The provided anhydrous matrix gel containing chitosan has high chitosan content, and comprises carbomer, polyethylene glycol, transdermal absorption agent, humectant, polyvinylpyrrolidone and pH regulator besides high chitosan content. Wherein, carbomer has important functions of thickening, bonding, emulsifying and the like as a gel matrix; polyethylene glycol is used as a hydrophilic solvent, and a hydroxyl group of the polyethylene glycol and a carboxyl group of carbomer form a hydrogen bond to swell the carbomer so as to form gel; the polyvinylpyrrolidone is an excellent film forming material, has good biocompatibility, cohesive force and the like, is used as a thickening agent to disperse chitosan, and is compatible with carbomer to ensure that the generated gel reticular structure is relatively loose, has more pore channels and is beneficial to increasing the drug dissolution; the chitosan swells in water, can be permanently adhered to and isolate the wound surface, and can be used as an effective component to play roles in stopping bleeding, easing pain, relieving edema and promoting healing. The components are compounded to obtain the anhydrous matrix gel with high chitosan content, and the anhydrous matrix gel can be applied to the field of medicine, for example, can be used as an external preparation for post-operative nursing of hemorrhoids.
According to an embodiment of the present invention, the anhydrous matrix gel containing chitosan provided above may further include the following technical features:
according to an embodiment of the invention, the carbomers are selected from at least one of carbomers 934, 940, 941.
According to an embodiment of the present invention, the polyethylene glycol is at least one selected from the group consisting of polyethylene glycol 200, polyethylene glycol 400, and polyethylene glycol 600.
According to an embodiment of the present invention, the polyvinylpyrrolidone is at least one of polyvinylpyrrolidone K30 and polyvinylpyrrolidone K90.
According to an embodiment of the present invention, the pH adjuster is selected from at least one of triethanolamine and sodium hydroxide.
According to an embodiment of the present invention, the transdermal enhancer is at least one of propylene glycol, peppermint oil, isopropyl myristate, and sorbitol.
According to an embodiment of the present invention, the humectant is at least one of glycerin, 1, 3-butanediol, 1, 2-pentanediol.
According to an embodiment of the invention, the deacetylation degree of the chitosan is 50-80%, and the molecular weight of the chitosan is 20000-60000 daltons.
According to an embodiment of the invention, the chitosan is a chitosan powder having a particle size of not more than 180 μm.
In a second aspect, the present invention provides an external pharmaceutical preparation comprising the chitosan-containing anhydrous base gel of the first aspect.
In a third aspect the present invention provides a method of preparing a chitosan-containing anhydrous matrix gel, the chitosan-containing anhydrous matrix gel referred to being the chitosan-containing anhydrous matrix gel of the first aspect of the invention, the method comprising:
dispersing carbomer in polyethylene glycol until complete swelling to obtain matrix a, and adding transdermal enhancer until stirring uniformly to obtain matrix b;
respectively adding a humectant and polyvinylpyrrolidone into a substrate b in sequence until the mixture is uniformly stirred to obtain a substrate c, and then dropwise adding a pH regulator into the substrate c to obtain a substrate d;
adding chitosan into the matrix d, and stirring uniformly to obtain the anhydrous matrix gel containing chitosan.
According to an embodiment of the present invention, the method described above may further include the following technical features:
according to an embodiment of the present invention, carbomers are dispersed in polyethylene glycol for 10-30 hours to fully swell.
According to an embodiment of the present invention, the transdermal absorption enhancer is added and stirred at 50-2000rpm for 5-300 minutes until uniformly stirred.
According to an embodiment of the present invention, the humectant and polyvinylpyrrolidone are added and stirred at 50-2000rpm for 5-300 minutes until uniformly stirred.
According to a fourth aspect of the present invention there is provided the use of a chitosan-containing anhydrous base gel according to the first aspect or a chitosan-containing anhydrous base gel prepared according to the method of the third aspect in the field of preparing a topical medicament.
The invention has the following beneficial effects:
(a) And (3) seepage management: the chitosan-containing anhydrous matrix gel provided by the invention contains a large amount of hydrophilic groups and loose reticular structures, can absorb and store a large amount of water, and is beneficial to realizing good seepage management;
(b) Adhesion: because the content of chitosan in the provided anhydrous matrix gel is high, the chitosan can be tightly adhered to and isolated from a wound surface after swelling in water, and can form effective protection for wound surface repair;
(c) Efficacy: the provided anhydrous matrix gel has relatively loose reticular structure and more pore channels, is beneficial to accelerating the dissolution of the medicine and improving the medicine release speed, has high chitosan content, and is beneficial to fully playing the effects of stopping bleeding, easing pain, relieving edema and promoting healing of the chitosan.
Drawings
FIG. 1 is a process flow diagram of a chitosan-containing anhydrous matrix gel prepared in accordance with an embodiment of the present invention;
FIG. 2 is a physical diagram of the anhydrous matrix gel containing chitosan prepared in example 1 according to the present invention;
FIG. 3 is a scanning electron microscope image of the anhydrous matrix gel containing chitosan prepared according to example 1 of the present invention;
FIG. 4 is a physical diagram of the anhydrous matrix gel containing chitosan prepared in comparative example 1 according to the present invention;
FIG. 5 is a physical diagram of the anhydrous matrix gel containing chitosan prepared in comparative example 2 according to the present invention;
FIG. 6 is a physical diagram of the anhydrous matrix gel containing chitosan prepared in comparative example 3 according to the present invention.
Detailed Description
The following describes the technical scheme of the present invention by examples. It should be noted that these examples are only for facilitating understanding of those skilled in the art and should not be construed as limiting the scope of the present invention.
The invention provides a chitosan-containing anhydrous matrix gel, which contains more than 5-15% of chitosan and does not contain water. The provided anhydrous matrix gel containing chitosan can be used as a carrier to realize high loading of insoluble medicine chitosan, so that the effects of stopping bleeding, easing pain, relieving edema and promoting healing of the chitosan are fully exerted. The gel without water matrix has even and fine texture, is easy to smear, swells when contacting water, can effectively absorb wound surface seepage, can permanently adhere to and isolate wound surfaces, and plays a role in protection. The anhydrous matrix gel prepared by the invention can be used for postoperative care of hemorrhoids.
According to a specific embodiment, the chitosan-containing anhydrous matrix gel is provided with a high chitosan content, for example up to 5-15% chitosan. According to a preferred embodiment of the invention, the chitosan content amounts to 6-12%, for example 8%.
In the invention, the deacetylation degree of the chitosan is 50-80%, the molecular weight of the chitosan is 20000-60000 daltons, and the chitosan is chitosan powder with the particle size not exceeding 180 mu m. The chitosan swells when meeting water, is tightly adhered to and isolates the wound surface, and has the effects of stopping bleeding, easing pain, relieving edema and promoting healing. The chitosan not only can improve the adhesiveness of red blood cells and form cell clots at bleeding sites, but also can generate or induce organisms to generate endothelin 1 to cause vasoconstriction, and can achieve the hemostatic effect even under the condition that a coagulation mechanism is blocked. In addition, chitosan can reduce the content of inflammatory substances such as Bradykinin (BK) and 5-hydroxytryptamine (5-HT) which cause pain, thereby acting to relieve pain in wounds and edema. The chitosan can also promote the macrophage to produce active factors which are beneficial to the wound healing, thereby promoting the wound healing. The effect can not be fully exerted when the using amount of the chitosan is low, and the gel is hard and difficult to smear when the using amount of the chitosan is large. The high content of chitosan in the anhydrous matrix gel can fully exert the effects, so that the chitosan can be applied to the field of pharmaceutical preparations, used as external preparations, used for painting or coating and the like.
According to an embodiment of the present invention, there is provided an anhydrous matrix gel containing chitosan, comprising, in parts by weight: 5-15 parts of chitosan, 0.5-3 parts of carbomer, 30-50 parts of polyethylene glycol, 20-30 parts of transdermal enhancer, 20-40 parts of humectant, 5-15 parts of polyvinylpyrrolidone and 0.5-2 parts of pH regulator. Carbomers as gel matrices have important roles in thickening, binding, emulsifying, etc.; polyethylene glycol is used as a hydrophilic solvent, and hydroxyl groups contained in the polyethylene glycol can form hydrogen bonds with carboxyl groups of carbomer to swell the carbomer to form a gel matrix; polyvinylpyrrolidone is an excellent film-forming material, and has good biocompatibility, cohesive force and the like, and the components can be compatible with high-content chitosan to form anhydrous matrix gel with a reticular loose structure, so that the effect of the chitosan, particularly the medicinal effect, is fully exerted. When the content of the contained components is changed, the texture of the prepared anhydrous matrix gel and the content of the chitosan capable of being compounded are influenced. For example, polyvinylpyrrolidone can increase the adhesive force of the gel, and when the amount is too low, the viscosity is low, so that the chitosan is unevenly dispersed, and when the amount is too high, the viscosity is high, and the spreadability is poor.
According to an embodiment of the present invention, the carbomer is one of carbomer 934, carbomer 940 and carbomer 941, and more preferably carbomer 940.
According to an embodiment of the present invention, the polyethylene glycol is one of polyethylene glycol 200, polyethylene glycol 400, and polyethylene glycol 600, and more preferably polyethylene glycol 400. Carbomer is dispersed in polyethylene glycol, and the carbomer can be swelled by forming hydrogen bonds with carboxyl groups of the carbomer through rich hydroxyl groups contained in the polyethylene glycol, so that a corresponding matrix is obtained and used as gel skeleton loaded chitosan.
According to a specific embodiment, the transdermal absorption agent mentioned is at least one of propylene glycol, peppermint oil, isopropyl myristate, sorbitol and the like. The use of these substances as transdermal absorption agents can help to enhance the penetration of the drug into the skin. According to a preferred embodiment, the transdermal enhancer is propylene glycol, which enhances the penetration of the drug into the skin by altering the structure of the stratum corneum or increasing the effect of the permeation enhancer on the stratum corneum.
According to a specific embodiment, the humectant mentioned is at least one of glycerin, 1, 3-butanediol, 1, 2-pentanediol, etc. The use of these humectants can provide viscosity to the substrate and can compromise spreadability. According to a preferred embodiment, the humectant is glycerin. The humectant is in a proper range, which can ensure the viscosity of the matrix and simultaneously give consideration to the spreadability. For example, glycerol is used in excessive amounts, the matrix is not sticky enough, the adhesive is poor, and the dosage is insufficient, the viscosity is too high, and the spreadability is poor. According to a preferred embodiment, glycerol is preferably used in an amount of 30-35%.
Polyvinylpyrrolidone is used as a thickener, and the adhesive strength of the gel can be improved by adding polyvinylpyrrolidone to the anhydrous base gel. According to a specific embodiment of the present invention, polyvinylpyrrolidone is used in an amount of 5 to 15%, more preferably 7 to 10%, still more preferably 8%. The polyvinylpyrrolidone is used as a thickener to improve the adhesive force of the gel, when the consumption is low, the viscosity of the system is low, local deposition occurs due to uneven dispersion of chitosan, and the excessive consumption has large viscosity of the system and poor spreadability. The polyvinylpyrrolidone used includes, but is not limited to, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, etc., preferably polyvinylpyrrolidone K90.
According to a specific embodiment, the pH regulator is at least one of triethanolamine and sodium hydroxide, and the dosage of the pH regulator is 0.5-2%; further preferably triethanolamine, preferably in an amount of 0.5 to 1%. Triethanolamine can be used as a pH regulator to neutralize carbomer to form salt, and the anions of the carbomer are dispersed and stretched to form an expanded state due to mutual repulsion of negative charges, so that gel is formed. The pH of the system is lower when the dosage of the triethanolamine is insufficient, the system has irritation to wound surfaces when the triethanolamine is used, and the viscosity of the system is reduced when the dosage is excessive, so that gel cannot be formed.
According to a specific embodiment, the content ratio of carbomer and pH regulator is (1-2): (0.5-1). Thus, gel formation can be ensured, and irritation to the wound surface is avoided.
According to one specific embodiment of the invention, the provided anhydrous matrix gel containing chitosan comprises the following components in percentage by mass: 0.5-3% (w/w)%, 30-50% (w/w) polyethylene glycol, 20-30% (w/w) transdermal enhancer, 20-40% (w/w) humectant, 5-15% (w/w) polyvinylpyrrolidone, 0.5-2% (w/w) pH regulator, and 5-15% (w/w) chitosan. The provided anhydrous matrix gel containing chitosan does not contain water.
The invention also provides a preparation method of the anhydrous matrix gel containing chitosan, which is shown by referring to figure 1 and comprises
Dispersing carbomer in polyethylene glycol until complete swelling to obtain matrix a, and adding transdermal enhancer until stirring uniformly to obtain matrix b;
respectively adding a humectant and polyvinylpyrrolidone into a substrate b in sequence until the mixture is uniformly stirred to obtain a substrate c, and then dropwise adding a pH regulator into the substrate c to obtain a substrate d;
adding chitosan into the matrix d, and stirring uniformly to obtain the anhydrous matrix gel containing chitosan. The preparation method provided by the invention has simple process, can be carried out at room temperature, has universality and can prepare gel in a large scale.
According to a specific embodiment, the swelling time of the carbomer in polyethylene glycol is 10-30 hours, more preferably 18-24 hours, still more preferably 20 hours, and the swelling temperature is preferably room temperature. The gel matrix can be uniformly dispersed in the hydrophilic solvent by swelling carbomer in polyethylene glycol.
According to a specific embodiment, the stirring time after the components such as transdermal enhancer, humectant and polyvinylpyrrolidone are added to the system is 5 to 300 minutes, more preferably 5 to 200 minutes, still more preferably 5 to 80 minutes, respectively; after the addition of the components, the stirring is carried out uniformly at a stirring speed of 50 to 2000rpm, more preferably 100 to 1500rpm, still more preferably 100 to 800rpm. The stirring apparatus to be used is not particularly limited, and any apparatus known to those skilled in the art or commonly used in the art may be used.
In at least some embodiments of the present invention, provided methods of making include: firstly dispersing carbomer in polyethylene glycol for 10-30 hours until the carbomer is fully swelled to obtain a matrix a, then dripping transdermal enhancer and stirring for 5-300 minutes at 50-2000rpm to obtain a matrix b, then adding humectant and stirring for 5-300 minutes at 50-2000rpm until the carbomer is uniform, then placing polyvinylpyrrolidone in the system, stirring for 5-300 minutes at 50-2000rpm to obtain a matrix c, dripping pH regulator in a stirring state at 50-2000rpm after the carbomer is uniformly dispersed to obtain a matrix d, and finally adding chitosan in the system and stirring uniformly to obtain the anhydrous matrix gel containing chitosan.
The invention also provides application of the anhydrous matrix gel containing chitosan in the field of medicines, in particular in the field of external medicine. The application operation of the chitosan-containing anhydrous matrix gel in the medical technical field is not particularly limited, and the application operation well known to the person skilled in the art can be adopted.
The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. The source of the raw materials is not particularly limited, and commercially available products known to those skilled in the art may be used.
Example 1
The embodiment provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in percentage by mass:
carbomer 940 1%, glycerol 30%, propylene glycol 20%, polyethylene glycol 400.5%, polyvinylpyrrolidone K90%, triethanolamine 0.5% and chitosan 12%.
Referring to fig. 1, the preparation method comprises:
weighing polyethylene glycol 400 and placing in a beaker for standby; weighing carbomer 940, slowly dispersing into polyethylene glycol 400, stirring with a glass rod for 5min, standing for 20h to fully swell carbomer to obtain matrix a;
propylene glycol is dropwise added into the matrix a, and a glass rod is used for stirring while the propylene glycol is dropwise added, and the matrix b is obtained after uniform mixing;
adding glycerol into the matrix b, stirring uniformly by using a glass rod, and then continuously adding polyvinylpyrrolidone K90, and uniformly mixing by using the glass rod to obtain a matrix c;
dropwise adding triethanolamine into the substrate c, stirring by using a glass rod while dropwise adding, and uniformly mixing to obtain a substrate d;
and adding chitosan into the matrix d, and uniformly stirring by using a glass rod to obtain the anhydrous matrix gel containing chitosan.
Referring to fig. 1, the gel matrix is swelled in a hydrophilic solvent, and then a transdermal enhancer, a humectant, a thickener, a pH regulator and chitosan are added in sequence to obtain the anhydrous matrix gel containing chitosan.
A physical diagram of the anhydrous matrix gel containing chitosan prepared in example 1 is shown in FIG. 2. As can be seen from FIG. 2, the chitosan-containing anhydrous base gel prepared in example 1 has uniform texture, and is smooth and fine. The scanning electron microscope image of the anhydrous matrix gel containing chitosan prepared in the example 1 is shown in fig. 3; as can be seen from fig. 3, the anhydrous matrix gel containing chitosan prepared in example 1 has a loose network structure, which is beneficial to drug dissolution.
Reference YY/T0471.1-2004 section 1 of the contact wound dressing test method: liquid absorbency 3.2 test the liquid absorption fold was tested on example 1 and on a commercially available gel (commercially available silver Hua Tang medical chitosan hemorrhoid gel) by the following method:
1g of the sample is weighed and placed in a centrifuge tube, purified water preheated to 37 ℃ is added, the mass of the purified water is 40 times of that of the sample, the centrifuge tube is sealed and then is transferred into a drying box, the sample is kept at 37 ℃ for 24 hours, the sample is hung for 30 seconds after being taken out, and the mass of the sample is weighed to be m. The liquid absorption multiple is calculated as follows:
imbibition multiple = (m-1)/1
The gel prepared in example 1 has a liquid absorption multiple of 6 times and the commercial gel has a liquid absorption multiple of < 1 time, and the results show that the preparation method provided by the invention is simple in process and can realize better liquid permeation management.
Taking the anhydrous matrix gel prepared in example 1 as an example, when the anhydrous matrix gel prepared in example 1 is used according to the frequency of 3 g/count and 1-2 times/day in the external hemorrhoid restoration, the application of the anhydrous matrix gel to patients for 3 days is obviously improved.
Example 2
The embodiment provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in percentage by mass:
carbomer 941%, glycerol 30%, propylene glycol 20%, polyethylene glycol 600, polyvinylpyrrolidone K90 9%, sodium hydroxide 1% and chitosan 10%.
The preparation method comprises the following steps:
weighing polyethylene glycol 600 and placing in a beaker for standby; weighing carbomer 941, slowly dispersing into polyethylene glycol 600, stirring with a glass rod for 10min, standing for 24h, and fully swelling carbomer 941 to obtain matrix a;
propylene glycol is dropwise added into the matrix a, and a glass rod is used for stirring while the propylene glycol is dropwise added, and the matrix b is obtained after uniform mixing;
adding glycerol into the matrix b, stirring uniformly by using a glass rod, then continuously adding polyvinylpyrrolidone K90, and uniformly mixing by using the glass rod to obtain a matrix c;
dropwise adding 1% sodium hydroxide into the matrix c, stirring by using a glass rod while dropwise adding, and uniformly mixing to obtain a matrix d;
adding 10% of chitosan into the matrix d, and uniformly stirring by using a glass rod to obtain the anhydrous matrix gel containing chitosan.
The gel prepared in example 2 was tested in parallel 3 times according to the test method of example 1, and the average value of the imbibition factor was 5 times.
Example 3
The embodiment provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in percentage by mass:
carbomer 940 1%, glycerol 30%, propylene glycol 20%, polyethylene glycol 400%, polyvinylpyrrolidone K90 10%, triethanolamine 1% and chitosan 8%.
The preparation method comprises the following steps:
weighing polyethylene glycol 400 and placing in a beaker for standby; weighing 1% carbomer 940, slowly dispersing into polyethylene glycol 400, stirring with a glass rod for 5min, standing for 19h to make carbomer 940 fully swell to obtain matrix a;
propylene glycol is dropwise added into the matrix a, and a glass rod is used for stirring while the propylene glycol is dropwise added, and the matrix b is obtained after uniform mixing;
adding glycerol into the matrix b, stirring uniformly by using a glass rod, then continuously adding polyvinylpyrrolidone K90, and uniformly mixing by using the glass rod to obtain a matrix c;
dropwise adding triethanolamine into the substrate c, stirring by using a glass rod while dropwise adding, and uniformly mixing to obtain a substrate d;
and adding chitosan into the matrix d, and uniformly stirring by using a glass rod to obtain the anhydrous matrix gel containing chitosan.
The gel prepared in example 3 was tested in parallel 3 times according to the test method of example 1, and the average value of the imbibition factor was 4 times.
Example 4
The embodiment provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in percentage by mass:
carbomer 940 1%, glycerol 32%, propylene glycol 20%, polyethylene glycol 400, polyvinylpyrrolidone K90 8%, triethanolamine 1% and chitosan 8%.
The preparation method comprises the following steps:
weighing polyethylene glycol 400 and placing in a beaker for standby; weighing 1% carbomer 940, slowly dispersing into polyethylene glycol 400, stirring with a glass rod for 5min, standing for 22h, and fully swelling carbomer 940 to obtain matrix a;
propylene glycol is dropwise added into the matrix a, and a glass rod is used for stirring while the propylene glycol is dropwise added, and the matrix b is obtained after uniform mixing;
adding glycerol into the matrix b, stirring uniformly by using a glass rod, then continuously adding polyvinylpyrrolidone K90, and uniformly mixing by using the glass rod to obtain a matrix c;
dropwise adding triethanolamine into the substrate c, stirring by using a glass rod while dropwise adding, and uniformly mixing to obtain a substrate d;
and adding chitosan into the matrix d, and uniformly stirring by using a glass rod to obtain the anhydrous matrix gel containing chitosan.
The gel prepared in example 4 was tested in parallel 3 times according to the test method of example 1, and the average value of the imbibition factor was 4 times.
Example 5
The embodiment provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in percentage by mass:
carbomer 940 1%, glycerol 35.5%, propylene glycol 20%, polyethylene glycol 600% 30%, polyvinylpyrrolidone K30% 8%, triethanolamine 0.5% and chitosan 5%.
The preparation method comprises the following steps:
weighing polyethylene glycol 600 and placing in a beaker for standby; weighing 1% carbomer 940, slowly dispersing into polyethylene glycol 600, stirring with a glass rod for 7min, standing for 20 hr to make carbomer 940 fully swell to obtain matrix a;
propylene glycol is dropwise added into the matrix a, and a glass rod is used for stirring while the propylene glycol is dropwise added, and the matrix b is obtained after uniform mixing;
adding glycerol into the matrix b, stirring uniformly by using a glass rod, then continuously adding polyvinylpyrrolidone K30, and uniformly mixing by using the glass rod to obtain a matrix c;
dropwise adding triethanolamine into the substrate c, stirring by using a glass rod while dropwise adding, and uniformly mixing to obtain a substrate d;
and adding chitosan into the matrix d, and uniformly stirring by using a glass rod to obtain the anhydrous matrix gel containing chitosan.
The gel prepared in example 5 was tested in parallel 3 times according to the test method of example 1, and the average value of the imbibition factor was 3 times.
Comparative example 1
The comparative example 1 provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in mass fraction:
carbomer 940 1%, glycerol 35%, propylene glycol 20%, polyethylene glycol 400, hypromellose 3%, triethanolamine 1% and chitosan 10%.
An anhydrous matrix gel containing chitosan was prepared by the preparation method of reference example 1, substituting polyvinylpyrrolidone K90 with hypromellose. Hypromellose is also a common thickener, and increases the fluid volume of the polymer itself by forming hydrogen bonds, and reduces the space for free movement of particles, thereby increasing the viscosity of the system. The poor compatibility between the cationic polymer chitosan and the anionic polymer carbomer resulted in a decrease in the viscosity of the gel system, and the hypromellose was added in this comparative example 1, but the hypromellose was not swollen or dissolved in the system and thus did not provide an effective thickening effect, and the system was in a liquid state. A physical diagram of the anhydrous matrix gel containing chitosan prepared by comparative example 1 is shown in FIG. 4.
Comparative example 2
The comparative example 2 provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in mass fraction:
carbomer 940 1%, glycerol 35%, propylene glycol 20%, polyethylene glycol 400, polyvinylpyrrolidone K90 3%, triethanolamine 1% and chitosan 10%.
The content of polyvinylpyrrolidone K90 in this comparative example was set to 3%, and the production method was as described in example 1. The low dosage of polyvinylpyrrolidone K90 in the system can not provide the cohesive force of gel, and the uneven dispersion of chitosan can generate local deposition and obvious layering phenomenon. A physical diagram of the anhydrous matrix gel containing chitosan prepared by comparative example 2 is shown in FIG. 5.
Comparative example 3
The comparative example provides a chitosan-containing anhydrous matrix gel, which comprises the following raw materials in percentage by mass:
carbomer 940 1%, glycerol 31.5%, propylene glycol 20%, polyethylene glycol 400, polyvinylpyrrolidone K90 8%, triethanolamine 1.5% and chitosan 8%.
The triethanolamine content in this comparative example was set to 1.5% and the preparation method was as described in example 1. The mass ratio of triethanolamine to carbomer in the system is 3:2, the excessive triethanolamine breaks the crosslinking structure of carbomer, carbomer can not be precipitated to form gel, and the physical diagram of the anhydrous matrix gel containing chitosan prepared by the comparative example 3 is shown in figure 6.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. An anhydrous matrix gel containing chitosan, characterized by comprising, in parts by weight:
5-15 parts of chitosan,
0.5-3 parts of carbomer,
30-50 parts of polyethylene glycol,
20-30 parts of transdermal absorption agent,
20-40 parts of humectant, namely,
5-15 parts of polyvinylpyrrolidone, and
0.5-2 parts of pH regulator.
2. The chitosan-containing anhydrous matrix gel of claim 1, wherein the carbomer is selected from at least one of carbomers 934, 940, 941.
3. The chitosan-containing anhydrous matrix gel of claim 1, wherein the polyethylene glycol is selected from at least one of polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600.
4. The chitosan-containing anhydrous matrix gel of claim 1, wherein the pH adjuster is at least one of triethanolamine, sodium hydroxide;
the transdermal absorption agent is at least one of propylene glycol, peppermint oil, isopropyl myristate and sorbitol;
the humectant is at least one of glycerol, 1, 3-butanediol and 1, 2-pentanediol.
5. The chitosan-containing anhydrous matrix gel of claim 1, wherein the polyvinylpyrrolidone is one of polyvinylpyrrolidone K30, polyvinylpyrrolidone K90.
6. The chitosan-containing anhydrous matrix gel according to claim 1, wherein the chitosan has a degree of deacetylation of 50-80%, a molecular weight of 20000-60000 daltons, and a particle size of not more than 180 μm.
7. An external pharmaceutical preparation, characterized in that it comprises the chitosan-containing anhydrous base gel according to any one of claims 1 to 6.
8. A method of preparing the chitosan-containing anhydrous base gel of any one of claims 1-6, comprising:
dispersing carbomer in polyethylene glycol to be fully swelled so as to obtain a matrix a, and then adding a transdermal enhancer to be uniformly stirred so as to obtain a matrix b;
respectively adding a humectant and polyvinylpyrrolidone into a substrate b in sequence until the mixture is uniformly stirred to obtain a substrate c, and then dropwise adding a pH regulator into the substrate c to obtain a substrate d;
adding chitosan into the matrix d, and stirring uniformly to obtain the anhydrous matrix gel containing chitosan.
9. The method of claim 8, wherein the step of determining the position of the first electrode is performed,
carbomers are dispersed in polyethylene glycol for 10-30 hours to fully swell;
adding transdermal enhancer, stirring at 50-2000rpm for 5-300 min until stirring;
the humectant and polyvinylpyrrolidone are added and stirred at 50-2000rpm for 5-300 minutes until uniformly stirred.
10. Use of the chitosan-containing anhydrous matrix gel according to any one of claims 1 to 6 or the chitosan-containing anhydrous matrix gel prepared according to the method of claim 8 or 9 in the field of preparing a topical medicament.
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