CN114469985B - Dendrobium nobile medicinal composition and preparation method of antibacterial gel thereof - Google Patents
Dendrobium nobile medicinal composition and preparation method of antibacterial gel thereof Download PDFInfo
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- CN114469985B CN114469985B CN202011148961.9A CN202011148961A CN114469985B CN 114469985 B CN114469985 B CN 114469985B CN 202011148961 A CN202011148961 A CN 202011148961A CN 114469985 B CN114469985 B CN 114469985B
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- 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
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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Abstract
The invention provides a dendrobium nobile pharmaceutical composition and a preparation method of antibacterial gel thereof. The pharmaceutical composition comprises a compound of formula I or a pharmaceutically acceptable salt or solvate thereof and a polysaccharide compound, wherein the polysaccharide compound comprises D-glucuronic acid and D-galactose in a molar ratio of between 5:1 and 0.5:1, the polysaccharide compound has a molecular weight in the range of between 2000Da and 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is between 10:1 and 1:10. The medicinal composition has good antibacterial or bacteriostatic activity and skin repairing activity, can be used for preparing gel, and the prepared gel is safe and reliable to a human body, has no toxic or side effect, has no irritation to mucous membrane, and can be used for nursing and repairing skin trauma.
Description
Technical Field
The invention relates to the technical field of natural medicines, in particular to a dendrobium nobile medicinal composition and a preparation method of antibacterial gel thereof.
Background
In daily life, people often suffer from skin trauma damage such as bruise, scratch, gouge, bruise and the like, and if the skin trauma is not treated in time, the skin trauma can be red, swollen, inflamed, whitened, purulent and the like due to invasion of external bacteria, so that the wound is difficult to heal, and even a scar is left. Slight skin injury usually does not need to go to a hospital, and the external preparation can be selected and applied by self. The raw materials of the existing common external ointment are usually antibiotics and even hormones mainly, such as erythromycin ointment, dermatitis and the like. The medicines generally have certain side effects, such as dermatitis flat instruction book clearly marks that the long-term use of the medicines can cause secondary bacterial and fungal infection, local acne, wine-like dermatitis, skin atrophy and telangiectasis can occur, and the medicines can have the reactions of itching, pigmentation, facial erythema, wound healing disorder and the like, and the traditional Chinese medicines as natural sources have good pharmacological effects, particularly have small side effects and are popular with consumers.
The traditional Chinese medicine dendrobium nobile (Dendrobium nobile Lindl.) is also called herba polygoni avicularis, radix polygoni multiflori and the like, is a plant of the genus dendrobium in the family of orchidaceae, is a traditional and famous and precious medicinal plant in China, is listed as a top grade as early as in Shennong Ben Cao Jing, and is known as one of nine-herb. The medicinal part is fresh or dry stem, and has effects of strengthening yin, replenishing vital essence, thickening intestine and stomach, and reducing weight for prolonging life. Modern pharmacological researches show that the main active ingredients of dendrobium nobile lindl are alkaloids and polysaccharide compounds, and have multiple effects of resisting tumor, resisting oxidation and aging, enhancing immunity, regulating gastrointestinal movement, reducing blood sugar and blood fat and the like. Earlier studies have found that a dendrobium nobile polysaccharide (patent application number: 202010152786.4) has good moisturizing effect.
The topical ointments used for treating skin injuries in the prior art have the following defects:
Defect one: allergic reactions. The side effects of anaphylactic reaction are all different from person to person, and some people can generate strong anaphylactic reaction after using the medicine, and once anaphylactic reaction occurs, the medicine application should be stopped in time so as to avoid more harm to themselves.
Defect two: can easily cause skin dryness after long-term use.
Defect three: the process is complex and the cost is high.
Defect four: drug resistance. Drug resistance, also known as drug resistance, generally refers to the decrease or even disappearance of the sensitivity of a pathogen to a drug after multiple contacts of the pathogen with the drug, resulting in a decrease or inefficiency of the drug's therapeutic effect on the pathogen. For example, erythromycin can also develop resistance, and is very effective when it is initially used, but the effect is significantly reduced after a period of use, which is an indication of developing resistance. In addition, bacteria can also produce cross-resistance to other antibiotics of the class of erythromycin, such as azithromycin, erythromycin ethylsuccinate, roxithromycin.
For the above reasons, further researches on external ointments for treating skin injury are needed to solve the problems that common external ointments are easy to generate anaphylactic reaction, are easy to cause skin dryness after long-term use, have complex process and high cost, and are easy to generate drug resistance.
Disclosure of Invention
The invention mainly aims to provide a dendrobium nobile medicinal composition and a preparation method of antibacterial gel thereof, which are used for solving the problems that common external paste in the prior art is easy to cause anaphylactic reaction, is easy to cause dry skin after long-term use, has complex process and high cost, and is easy to generate drug resistance.
In order to achieve the above object, according to one aspect of the present invention, there is provided a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt or solvate thereof, and a polysaccharide compound, wherein the polysaccharide compound comprises D-glucuronic acid and D-galactose in a molar ratio of 5:1 to 0.5:1, the polysaccharide compound has a molecular weight in the range of 2000Da to 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is 10:1 to 1:10.
Wherein the compound of formula I has the following structural formula
Further, the pharmaceutical composition also comprises pharmaceutically acceptable pharmaceutical excipients.
Further, the pharmaceutical excipients are selected from one or more of diluents, antioxidants, suspending agents and emulsifiers.
Further, the polysaccharide compound has the following structure:
Wherein n is 6, 7 or 8.
Further, the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:9.
Further, the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:8.
Further, the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:7.
Further, the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:6.
Further, the weight ratio of the compound of formula I to the polysaccharide compound is 1:6.
According to another aspect of the present invention there is provided the use of a pharmaceutical composition according to the above for the preparation of an antibacterial or bacteriostatic agent.
According to another aspect of the present invention there is provided the use of a pharmaceutical composition as described above for the manufacture of a medicament for the treatment of skin disorders.
According to another aspect of the present invention, there is provided a method of preparing a pharmaceutical composition, the method comprising the steps of:
1) Adding a compound of the formula I and a pharmaceutical adjuvant to a first solvent to obtain a first mixture;
2) Adding a polysaccharide compound and the pharmaceutical excipients to a second solvent to obtain a second mixture; and
3) Mixing the first mixture and the second mixture to obtain the pharmaceutical composition,
Wherein the polysaccharide compound comprises D-glucuronic acid and D-galactose in a molar ratio of 5:1 to 0.5:1, the polysaccharide compound has a molecular weight in the range of 2000Da to 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is 10:1 to 1:10;
wherein the compound of formula I has the following structural formula
Further, the pharmaceutical excipients are selected from one or more of diluents, antioxidants, suspending agents and emulsifiers.
Further, the pharmaceutical auxiliary material is selected from one or more of sodium hydroxymethyl cellulose, carbomer, polyvinyl alcohol, hydroxyethyl cellulose, sodium alginate, chitin, chitosan, hydroxypropyl methyl cellulose, ethyl cellulose, agar, hydroxyethyl methyl cellulose, hydroxypropyl cellulose, beeswax, xanthan gum, acacia, casein and methyl cellulose.
Further, the second solvent is further added in step 3).
Further, the first solvent and the second solvent are the same or different.
Further, the first solvent is selected from one or more of a C 1～C4 alcohol, a glycol, an ether, water, formic acid, and acetic acid.
Further, the second solvent is selected from one or more of C 1～C4 alcohols, glycols, ethers, water, formic acid, and acetic acid.
The pharmaceutical composition of the invention comprises a compound of formula I or a pharmaceutically acceptable salt or solvate thereof and a polysaccharide compound, wherein the polysaccharide compound comprises D-glucuronic acid and D-galactose, the molar ratio of the D-glucuronic acid to the D-galactose is 5:1 to 0.5:1, the molecular weight of the polysaccharide compound is in the range of 2000Da to 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is 10:1 to 1:10. The pharmaceutical composition has good antibacterial and bacteriostatic activity and wound healing promoting effects, and can be used for traumatic skin repair, so that the problems that common external ointment is easy to cause anaphylactic reaction, skin dryness is easy to cause after long-term use, the process is complex, the cost is high and drug resistance is easy to generate can be well solved.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for the description of the embodiments will be briefly described below, and it will be apparent that the drawings in the following description are only some embodiments of the present application, and that other drawings can be obtained according to these drawings by those skilled in the art without departing from the scope of the claimed application.
FIG. 1 is a HPGPC chromatogram of a polysaccharide compound according to the present invention.
FIG. 2 is an infrared absorption spectrum of a polysaccharide compound according to the present invention.
Detailed Description
The following description of the embodiments of the present application will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are some, but not all embodiments of the application. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
It should be noted that, without conflict, the embodiments of the present application and features of the embodiments may be combined with each other. The present application will be described in detail with reference to examples.
The application is described in further detail below in connection with specific examples which are not to be construed as limiting the scope of the application as claimed.
As described in the background section, the existing topical ointments are prone to allergic reactions, dry skin after long-term use, complex processes, high costs and susceptibility to drug resistance. In order to solve the above problems, the present invention provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt or solvate thereof and a polysaccharide compound, wherein the polysaccharide compound comprises D-glucuronic acid and D-galactose in a molar ratio of 5:1 to 0.5:1, the polysaccharide compound has a molecular weight in the range of 2000Da to 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is 10:1 to 1:10.
Wherein the compound of formula I is dendrobine (dendrobine), which has the following structure:
The compounds of formula I above may be converted into pharmaceutically acceptable salts or solvates thereof, preferably acid addition salts, such as hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, mesylate or p-toluenesulfonate salts.
The compounds of formula I may exist as stereoisomers. It is to be understood that the present invention includes the use of all geometric and optical isomers of the compounds of formula I, as well as mixtures thereof, including racemic compounds. The use of tautomers and mixtures thereof also forms one aspect of the invention.
The compounds of formula I or pharmaceutically acceptable salts or solvates thereof are typically administered to mammals, including humans, in the form of the usual pharmaceutical compositions, for example capsules, microcapsules, tablets, granules, powders, lozenges, syrups, aerosols, inhalants, solutions, injections, suspensions, emulsions, suppositories and the like, and the most suitable dosage form is a suspension.
The pharmaceutical compositions comprising a compound of formula I or a pharmaceutically acceptable salt or solvate thereof and a polysaccharide compound may be administered topically, for example topically to the skin, and the pharmaceutical compositions may be in the form of solutions, suspensions, aerosols and dry powder formulations; or systemic, for example oral, in the form of tablets, capsules, syrups, powders or granules, or parenteral, in the form of solutions or suspensions, or subcutaneous or rectal suppositories, or transdermal.
For topical administration, the active substance is suitably used in the form of ointments, medicated wine, emulsions, solutions, lotions, sprays, suspensions, etc. Ointments, emulsions and solutions are preferred. These agents for topical application may be prepared by mixing the product as the active ingredient with a non-toxic, inert solid or liquid carrier commonly used in these formulations and suitable for topical treatment.
In a preferred embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable pharmaceutical excipient.
In a preferred embodiment, the pharmaceutical excipients are selected from one or more of diluents, antioxidants, suspending agents and emulsifiers.
Wherein the diluent is one or more of vegetable oil, propylene glycol, polyethylene glycol (molecular weight 200-8000) and mineral oil.
The antioxidant is one or more of L-cysteine hydrochloride, dithioglycollic acid, ethylenediamine tetraacetic acid disodium salt, malic acid, glutathione, D-xylose, glycine, alpha-tocopherol, alpha-tocopheryl acetate, sodium sulfite, inositol, ascorbic acid, phytic acid, dibutyl hydroxytoluene, sodium ascorbate, lecithin, hydroquinone, xylitol, gluconic acid-delta-lactone, succinic acid, sodium metabisulfite and ethylenediamine tetraacetic acid.
The suspending agent is one or more of sodium hydroxymethyl cellulose, carbomer, polyvinyl alcohol, hydroxyethyl cellulose, sodium alginate, chitin, chitosan, hydroxypropyl methylcellulose, ethyl cellulose, agar, hydroxyethyl methylcellulose, hydroxypropyl cellulose, beeswax, xanthan gum, acacia, casein, and methylcellulose.
The emulsifier is one or more of methylcellulose, glyceryl monostearate, hydroxylated lecithin, acetylated monoglyceride, diethylene glycol distearate, trihydroxymethane, casein, ethylene glycol monostearate, ethyl hydroxyethyl cellulose, diacetyl monoglyceride, fatty acid glyceride acetate, xylitol anhydride monooleate, propylene glycol alginate and triglycerol monolaurate.
In a preferred embodiment, the polysaccharide compound is a dendrobium nobile polysaccharide having the following structure:
Wherein n is 6, 7 or 8.
In order to further enhance the synergistic effect of the two components of the pharmaceutical composition, i.e. to enhance the antibacterial or bacteriostatic activity of the pharmaceutical composition and to significantly shorten the wound healing time, in a preferred embodiment the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:9.
In a preferred embodiment, the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:8.
In a preferred embodiment, the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:7.
In a preferred embodiment, the weight ratio of the compound of formula I to the polysaccharide compound is from 10:1 to 1:6.
In a preferred embodiment, the weight ratio of the compound of formula I to the polysaccharide compound is 1:6.
According to another aspect of the present invention there is provided the use of a pharmaceutical composition according to the above for the preparation of an antibacterial or bacteriostatic agent.
In a preferred embodiment, the pathogen includes, but is not limited to, one or more of the following: staphylococcus aureus MRSA, staphylococcus aureus MSSA, staphylococcus epidermidis MRSE, staphylococcus epidermidis resistant strain MSSE, pneumococcus, escherichia coli, klebsiella pneumoniae, pseudomonas aeruginosa, staphylococcus aureus ATCC25925 and escherichia coli ATCC25922.
According to another aspect of the present invention there is provided the use of a pharmaceutical composition as described above for the manufacture of a medicament for the treatment of skin disorders.
In a preferred embodiment, the above pharmaceutical composition is also suitable for the topical and systemic treatment of acne, psoriasis and other keratinized skin diseases with enhanced or pathologically altered, local and systemic treatment of inflammatory and allergic skin conditions. In addition, the above pharmaceutical compositions may also be used to control mucosal disorders with inflammatory or degenerative or transforming changes. Furthermore, the above pharmaceutical composition, preferably in the form of a topical formulation, can be used for the treatment of slightly or severely damaged skin (skin ageing).
In the present invention, the term "treatment" also includes "prophylaxis" unless there is a specific description of the contrary. The terms "therapeutic" and "therapeutic" should be understood accordingly.
The present invention also provides a method of treating a skin disorder, which comprises administering to said patient a therapeutically effective amount of a compound of formula I as defined above, or a pharmaceutically acceptable salt or solvate thereof, and a therapeutically effective amount of a polysaccharide compound as defined above.
The present invention also provides a method of treating inflammatory and allergic skin diseases which comprises administering to said patient a therapeutically effective amount of a compound of formula I as defined above or a pharmaceutically acceptable salt or solvate thereof and a therapeutically effective amount of a polysaccharide compound as defined above.
The present invention also provides a method of treating mild or severe skin damage comprising administering to said patient a therapeutically effective amount of a compound of formula I as defined above, or a pharmaceutically acceptable salt or solvate thereof, and a therapeutically effective amount of a polysaccharide compound as defined above.
Of course, for the therapeutic uses described above, the amount of drug administered will vary depending on the compound used, the mode of administration, the treatment desired and the disease for which it is indicated. The daily dosage of the compounds of formula I as defined above may be from 0.001mg/kg to 100mg/kg. The daily dosage of polysaccharide compound as defined above may be from 0.001mg/kg to 100mg/kg.
According to another aspect of the present invention, there is provided a method of preparing a pharmaceutical composition, the method comprising the steps of:
1) Adding a compound of the formula I and a pharmaceutical adjuvant to a first solvent to obtain a first mixture;
2) Adding a polysaccharide compound and the pharmaceutical excipients to a second solvent to obtain a second mixture; and
3) Mixing the first mixture and the second mixture to obtain the pharmaceutical composition,
Wherein the polysaccharide compound comprises D-glucuronic acid and D-galactose in a molar ratio of 5:1 to 0.5:1, the polysaccharide compound has a molecular weight in the range of 2000Da to 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is 10:1 to 1:10;
wherein the compound of formula I is dendrobine (dendrobine), which has the following structure:
in a preferred embodiment, the polysaccharide compound is a dendrobium nobile polysaccharide having the following structure:
Wherein n is 6, 7 or 8.
In a preferred embodiment, the pharmaceutical excipients are selected from one or more of diluents, antioxidants, suspending agents and emulsifiers.
In a preferred embodiment, the pharmaceutical excipients are selected from one or more of sodium hydroxymethyl cellulose, carbomer, polyvinyl alcohol, hydroxyethyl cellulose, sodium alginate, chitin, chitosan, hydroxypropyl methylcellulose, ethyl cellulose, agar, hydroxyethyl methylcellulose, hydroxypropyl cellulose, beeswax, xanthan gum, acacia, casein and methylcellulose.
In a preferred embodiment, the pharmaceutical adjuvant is carbomer, the carbomer is acrylic acid crosslinked resin obtained by crosslinking pentaerythritol and the like with acrylic acid, the carbomer is a very important rheology modifier, and the neutralized carbomer is an excellent gel matrix and has important applications such as thickening, suspending and the like, and the pharmaceutical adjuvant has simple process and good stability and is widely applied to emulsion, cream and gel.
In a preferred embodiment, the second solvent is further added in step 3).
In a preferred embodiment, the first solvent and the second solvent are the same or different.
In a preferred embodiment, the first solvent is selected from one or more of a C 1～C4 alcohol, a glycol, an ether, water, formic acid, and acetic acid.
In a preferred embodiment, the second solvent is selected from one or more of a C 1～C4 alcohol, a glycol, an ether, water, formic acid, and acetic acid.
Examples
Preparation process of dendrobine (dendrobine)
Adding 15 times of 0.1% hydrochloric acid solution into dendrobium nobile medicinal material, leaching for 2 times, merging leaching solutions, adding NaOH to adjust Ph=8-10, adding equal amount of ethyl acetate for extraction, separating by silica gel column chromatography, eluting with n-hexane-acetone (50:1), and obtaining dendrobine with purity more than or equal to 90%.
Identification of dendrobine
1H-NMR(400MHz,CDCl3)δ:4.85(1H,dd,J＝5.4,3.1Hz),3.16(1H,t,J＝8.7Hz),2.72(1H,t,J＝8.7Hz),2.66(1H,d,J＝3.1Hz),2.50(3H,s),2.46(1H,t,J＝5.4Hz),2.38(1H,t,J＝8.7Hz),2.15(1H,m),2.13(1H,m),2.11(1H,m),2.06(1H,m),1.89(1H,m),1.85(1H,m),1.58(1H,m),1.41(3H,s),0.99(3H,d,J＝2.9Hz),0.98(3H,d,J＝2.9Hz);13C-NMR(100MHz,CDCl3)δ:20.3,21.0,24.9,31.0,32.7,32.9,36.5,43.3,44.2,51.6,52.7,53.9,62.2,67.1,79.6,179.3.
Preparation process of dendrobium nobile polysaccharide
The dendrobium nobile polysaccharide is prepared by a method of patent 'a dendrobium nobile polysaccharide with moisturizing effect', a preparation method and application (patent application number: CN 202010152786.4). Specifically, 1Kg of dendrobium nobile is taken, 15L of 0.5mol/L NaOH solution is added, and the mixture is stirred and extracted for 2 hours at 70 ℃; after cooling, adding 6mol/L HCl solution to adjust the pH value to 2.5; centrifuging to obtain supernatant. Concentrating the supernatant to about 1L, adding 4L of 95% edible ethanol, standing for 10 hours, centrifuging, and collecting precipitate to obtain 208g of dendrobium nobile lindl crude polysaccharide.
Identification of dendrobium nobile polysaccharide
200G of the dendrobium nobile lindl crude polysaccharide is taken, 1.6L of water is added for dissolution, and 0.5mol/L H O2 and 4.0mmol/L of acetic acid are added under the water bath of 30 ℃; after the reaction was completed for 4 hours, 130g of polysaccharide was obtained by ultrafiltration. High performance gel chromatography (HPGPC) was performed on a Sepax Mono GPC-10MP gel chromatographic column (4.6 mm 300mm,5 μm); taking 0.1mol/L sodium chloride as a mobile phase; the flow rate is 0.5mL/min; the column temperature is 30 ℃; the differential detector detects Dendrobium nobile polysaccharide (shown in figure 1) with molecular weight of 2500Da.
In addition, a proper amount of dendrobium nobile polysaccharide 3mg is taken, KBr powder 500mg is added, and the dendrobium nobile polysaccharide is uniformly ground, pressed into tablets, analyzed by an infrared spectrometer and absorbed by an infrared spectrum as shown in figure 2.
After 15mg of dendrobium nobile polysaccharide is added with deuterated pyridine for dissolution, the dendrobium nobile polysaccharide is analyzed by a nuclear magnetic resonance spectrometer, and 1H/13C-NMR data of the dendrobium nobile polysaccharide are shown in table 1.
TABLE 1 Dendrobium nobile polysaccharide 1H/13C-NMR Spectroscopy data and attribution
The pharmaceutical compositions claimed in the present invention are further described in detail by the following detailed description:
example 1: taking 1g of dendrobine, adding 10ml of absolute ethyl alcohol for dissolution, adding 50g of carbomer 934P, and uniformly grinding; and (3) adding 100ml of purified water into 10g of dendrobium nobile polysaccharide, dissolving, adding into the carbomer 934P, grinding uniformly, adding 900ml of purified water, and stirring uniformly to obtain gel 1.
Example 2: taking 10g of dendrobine, adding 50ml of absolute ethyl alcohol for dissolution, adding 50g of carbomer 934P, and uniformly grinding; and (3) dissolving 1g of dendrobium nobile polysaccharide in 50ml of purified water, adding the dissolved dendrobium nobile polysaccharide into the carbomer 934P, grinding uniformly, adding 950ml of purified water, and stirring uniformly to obtain gel 2.
Example 3: taking 3g of dendrobine, adding 10ml of absolute ethyl alcohol for dissolution, adding 50g of carbomer 934P, and uniformly grinding; and (3) adding 100ml of purified water into 4g of dendrobium nobile lindl polysaccharide, dissolving, adding into the carbomer 934P, grinding uniformly, adding 900ml of purified water, and stirring uniformly to obtain gel 3.
Example 4: taking 1g of dendrobine, adding 10ml of absolute ethyl alcohol for dissolution, adding 50g of carbomer 934P, and uniformly grinding; and (3) adding 100ml of purified water into 6g of dendrobium nobile lindl polysaccharide, dissolving, adding into the carbomer 934P, grinding uniformly, adding 900ml of purified water, and stirring uniformly to obtain gel 4.
Example 5: extracting 20g of dendrobium nobile with 400ml of purified water twice, mixing the extracting solutions, adding the extracting solutions into 50g of carbomer 934P, grinding uniformly, adding 300ml of purified water, and stirring uniformly to obtain gel 5.
Example 6: taking 10g of dendrobine, adding 50ml of absolute ethyl alcohol for dissolution, adding 50g of carbomer 934P, and uniformly grinding; 1000ml of purified water is added and stirred uniformly to obtain gel 6.
Example 7: taking 10g of dendrobium nobile polysaccharide, adding 100ml of purified water for dissolution, adding the dendrobium nobile polysaccharide into the carbomer 934P, grinding uniformly, adding 900ml of purified water, and stirring uniformly to obtain gel 7.
Example 8: different dendrobium nobile gel antibacterial or bacteriostatic activities
Sample: the gels 1 to 7 were prepared by the methods of examples 1 to 7, respectively.
Test strain:
The 40 strains of clinical pathogenic bacteria are selected, and the strain numbers are as follows: staphylococcus aureus MRSA 5 strain (numbered gold 1 to gold 5); staphylococcus aureus MSSA 5 strain (numbered gold 6 to gold 10); staphylococcus epidermidis MRSE 5 strain (numbered tables 1 to 5); staphylococcus epidermidis drug-resistant strain MSSE 5 strain (numbering tables 6 to 10); pneumococcus 5 strain (numbered lung 1-lung 5); escherichia coli 5 strain (numbered 1 to 5); klebsiella pneumoniae 5 strain (numbered g 1-g 5); pseudomonas aeruginosa 5 strain (numbered green 1-green 5). Staphylococcus aureus ATCC25925, escherichia coli ATCC25922 was additionally selected as a quality control strain.
Preparation of drug-containing plates:
Preparation of sample (i.e. gel 1-7) drug-containing plates: weighing a proper amount of samples respectively, placing the samples in a sterile mortar, adding sterile water for dissolution to obtain 40mg/ml solution, and adding 3ml of sterile water into 3ml of solution to obtain 20mg/ml solution; 3ml of sterile water is sequentially taken and added into the mixture for serial multiple dilution by the same method to obtain serial sample solutions with the concentrations of 4,2, 1, 0.5, 0.25, 0.125 and 0.0625mg/ml respectively.
1.5Ml of the sample solution is respectively taken and added into a 9cm sterile plate, 13.5ml of blood agar culture medium is added, the mixture is immediately and evenly mixed, and a horizontal table is arranged for coagulation to obtain a medicine-containing plate with the concentration of 0.4, 0.2, 0.1, 0.05, 0.025, 0.0125 and 0.00625mg/ml in sequence.
Preparing a bacterial suspension:
The fresh inclined plane strain of the test strain is taken, 2ml of nutrient broth (containing 5% sheep serum) culture medium is inoculated, the culture is carried out for 8 hours at 35 ℃, and the culture is subjected to turbidimetry with a No. 0.5 Mitsubishi turbidimetry tube, and the culture is properly diluted to the concentration of about 108CFU/ml for standby.
Inoculating and culturing:
The test bacterial suspensions are added into corresponding holes of a 96-well plate according to the serial number sequence and placed in a multipoint inoculator. Inoculating each prepared medicated plate according to the order of low concentration to high concentration. The cells were incubated at 35℃for 16 hours in an inverted state, and the observed results were taken out and recorded for growth. The results are shown in Table 2.
TABLE 2 different Dendrobium gel MIC measurement results (unit: mg/ml)
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"+" Indicates that the bacterial growth is not inhibited; "-" indicates that the bacterium did not grow and was inhibited.
The antibacterial test results show that: the pharmaceutical composition composed of the dendrobine and the dendrobium nobile polysaccharide has antibacterial or bacteriostatic activity superior to that of the dendrobine or the dendrobium nobile polysaccharide alone, wherein the antibacterial or bacteriostatic activity of the gels 2-4 prepared in examples 2-4 is obviously superior to that of the gels 1 and 6 prepared in examples 1 and 6, the antibacterial or bacteriostatic activity of the gel 4 prepared in example 4 is optimal, and under the experimental condition, the antibacterial activity of the dendrobium nobile extract and the gel prepared by the dendrobium nobile polysaccharide is not detected, so that the dendrobium nobile polysaccharide mainly plays a role in antibacterial sensitization of the dendrobine in the pharmaceutical composition.
Example 9: different dendrobium nobile gel promoting wound healing activity
Sample: the gels 1 to 7 were prepared by the methods of examples 1 to 7, respectively.
35C 57BL/6J mice with the age of 5 weeks are taken and divided into 7 groups, a square incision with the length of 0.5 multiplied by 1cm is made along the back and the tail of the mice, gel is smeared for 1 to 7 weeks for observation, the gel is smeared for 1 time every day, and the average wound healing time of each group of mice is observed. The results are shown in Table 3.
TABLE 3 different conditions of Dendrobium gel for promoting wound healing (Unit: tian)
| Gel 1 | Gel 2 | Gel 3 | Gel 4 | Gel 5 | Gel 6 | Gel 7 | |
| Healing time | 13 | 13 | 12 | 10 | - | - | 14 |
"-" Indicates that the wound did not heal.
The test result of promoting wound healing shows that: the pharmaceutical composition (gel 1-4) composed of the dendrobine and the dendrobine polysaccharide has better wound healing activity than the dendrobine polysaccharide (gel 7), wherein the gel 4 prepared in the example 4 has the shortest number of days for promoting wound healing, and under the experimental condition, no detection is made that the dendrobine extract and the dendrobine gel have the effect of promoting wound healing.
The foregoing is merely exemplary embodiments of the present application, and specific structures and features that are well known in the art are not described in detail herein. It should be noted that modifications and improvements can be made by those skilled in the art without departing from the scope of the application, which is also to be considered as the scope of the application, and which does not affect the effect of the application and the utility of the patent. The protection scope of the present application is subject to the content of the claims, and the description of the specific embodiments and the like in the specification can be used for explaining the content of the claims.
The foregoing has outlined rather broadly the more detailed description of embodiments of the application in order that the detailed description of the principles and embodiments of the application may be implemented in conjunction with the detailed description of embodiments of the application that follows. Meanwhile, based on the idea of the present application, those skilled in the art can make changes or modifications on the specific embodiments and application scope of the present application, which belong to the protection scope of the present application. In view of the foregoing, this description should not be construed as limiting the application.
Claims (14)
1. A pharmaceutical composition for bacteriostasis or antibiosis, characterized in that the drug in the pharmaceutical composition consists of a compound of formula I and a polysaccharide compound, wherein the polysaccharide compound consists of D-glucuronic acid and D-galactose, the molar ratio of D-glucuronic acid to D-galactose is 5:1 to 0.5:1, the molecular weight of the polysaccharide compound is in the range of 2000Da to 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is 1:6,
Wherein the compound of formula I has the following structural formula
Wherein the polysaccharide compound has the following structure:
Wherein n is 6, 7 or 8,
Wherein the bacteria are staphylococcus epidermidis MRSE, staphylococcus epidermidis drug-resistant strain MSSE and/or pneumococcus.
2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable pharmaceutical excipient.
3. The pharmaceutical composition according to claim 2, wherein the pharmaceutical excipients are selected from one or more of diluents, antioxidants, suspending agents and emulsifiers.
4. The pharmaceutical composition of claim 2, wherein the pharmaceutical excipient is carbomer.
5. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition is obtained by the following preparation method: taking 1g of dendrobine, adding 10ml of absolute ethyl alcohol for dissolution, adding 50g of carbomer 934P, and uniformly grinding; and (3) adding 100ml of purified water into 6g of dendrobium nobile lindl polysaccharide, dissolving, adding into the carbomer 934P, grinding uniformly, adding 900ml of purified water, and stirring uniformly to obtain the pharmaceutical composition.
6. Use of a pharmaceutical composition according to any one of claims 1 to 5 for the preparation of an antibacterial or bacteriostatic agent, characterized in that the bacteria are staphylococcus epidermidis MRSE, staphylococcus epidermidis resistant strain MSSE and/or pneumococcus.
7. A process for preparing a pharmaceutical composition according to any one of claims 1 to 5, characterized in that it comprises the steps of:
1) Adding a compound of the formula I and a pharmaceutical adjuvant to a first solvent to obtain a first mixture;
2) Adding a polysaccharide compound and the pharmaceutical excipients to a second solvent to obtain a second mixture; and
3) Mixing said first mixture and said second mixture to obtain said pharmaceutical composition,
Wherein the polysaccharide compound consists of D-glucuronic acid and D-galactose in a molar ratio of 5:1 to 0.5:1, the polysaccharide compound has a molecular weight in the range of 2000Da to 3000Da, and the weight ratio of the compound of formula I to the polysaccharide compound is 1:6,
Wherein the compound of formula I has the following structural formula
Wherein the polysaccharide compound has the following structure:
Wherein n is 6, 7 or 8.
8. The method of claim 7, wherein the pharmaceutical excipients are selected from one or more of diluents, antioxidants, suspending agents and emulsifiers.
9. The method according to claim 7, wherein the pharmaceutical excipients are selected from one or more of sodium hydroxymethyl cellulose, carbomer, polyvinyl alcohol, hydroxyethyl cellulose, sodium alginate, chitin, chitosan, hydroxypropyl methylcellulose, ethyl cellulose, agar, hydroxyethyl methylcellulose, hydroxypropyl cellulose, beeswax, xanthan gum, acacia, casein and methylcellulose.
10. The method according to claim 7, wherein the second solvent is further added in step 3).
11. The method of claim 7, wherein the first solvent and the second solvent are the same or different.
12. The method of claim 7, wherein the first solvent is selected from one or more of a C 1～C4 alcohol, a glycol, an ether, water, formic acid, and acetic acid.
13. The method of claim 7, wherein the second solvent is selected from one or more of a C 1～C4 alcohol, a glycol, an ether, water, formic acid, and acetic acid.
14. The method according to claim 7, characterized in that it comprises the steps of: taking 1g of dendrobine, adding 10ml of absolute ethyl alcohol for dissolution, adding 50g of carbomer 934P, and uniformly grinding; and (3) adding 100ml of purified water into 6g of dendrobium nobile lindl polysaccharide, dissolving, adding into the carbomer 934P, grinding uniformly, adding 900ml of purified water, and stirring uniformly to obtain the pharmaceutical composition.
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Citations (5)
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| CN105310933A (en) * | 2015-11-09 | 2016-02-10 | 铜仁市金农绿色农业科技有限公司 | Formula of active ingredients of anti-aging beauty mask |
| CN110585044A (en) * | 2019-10-14 | 2019-12-20 | 遵义医科大学 | Compound traditional Chinese medicine composition containing dendrobium stem and preparation method thereof |
| CN110585039A (en) * | 2019-09-24 | 2019-12-20 | 遵义医科大学 | Cosmetic composition containing dendrobium nobile fermentation extract and preparation method and application thereof |
| FR3085275A1 (en) * | 2018-08-28 | 2020-03-06 | Infinitus (China) Company Ltd. | Moisturizing composition and process for producing the same |
| CN111196864A (en) * | 2020-03-06 | 2020-05-26 | 遵义医科大学 | Dendrobium nobile polysaccharide with moisturizing effect and preparation method and application thereof |
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| CN105310933A (en) * | 2015-11-09 | 2016-02-10 | 铜仁市金农绿色农业科技有限公司 | Formula of active ingredients of anti-aging beauty mask |
| FR3085275A1 (en) * | 2018-08-28 | 2020-03-06 | Infinitus (China) Company Ltd. | Moisturizing composition and process for producing the same |
| CN110585039A (en) * | 2019-09-24 | 2019-12-20 | 遵义医科大学 | Cosmetic composition containing dendrobium nobile fermentation extract and preparation method and application thereof |
| CN110585044A (en) * | 2019-10-14 | 2019-12-20 | 遵义医科大学 | Compound traditional Chinese medicine composition containing dendrobium stem and preparation method thereof |
| CN111196864A (en) * | 2020-03-06 | 2020-05-26 | 遵义医科大学 | Dendrobium nobile polysaccharide with moisturizing effect and preparation method and application thereof |
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