CN110859875A - Phenytoin-silver compound medicine and external preparation prepared by using same - Google Patents
Phenytoin-silver compound medicine and external preparation prepared by using same Download PDFInfo
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- CN110859875A CN110859875A CN201911319672.8A CN201911319672A CN110859875A CN 110859875 A CN110859875 A CN 110859875A CN 201911319672 A CN201911319672 A CN 201911319672A CN 110859875 A CN110859875 A CN 110859875A
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- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/38—Silver; Compounds thereof
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/66—Papaveraceae (Poppy family), e.g. bloodroot
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
- A61K36/718—Coptis (goldthread)
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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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- A61K9/10—Dispersions; Emulsions
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
Abstract
The invention provides a phenytoin-silver compound medicine and an external preparation prepared by using the same, the compound medicine comprises phenytoin-silver, poppy shell, earthworm, pseudo-ginseng and coptis, and the mass ratio of the components is (10-30): (1-3): (3-10): (4-15): (4-15). The invention ensures that the medicine for promoting wound healing has wider treatment function and better curative effect. The invention enlarges the variety of the dosage forms of the phenytoin silver external compound preparation, and the obtained compound preparation has the advantages of relatively clear components, quick response, controllable quality, low toxicity and the like.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a phenytoin-silver compound medicine and an external preparation prepared by using the phenytoin-silver compound medicine.
Background
The skin is the largest organ of the human body, which protects various tissues and organs in the body from physical, mechanical, chemical and pathogenic microbial attacks. When the skin is damaged and the wound is large, the wound is difficult to heal quickly, external viruses and harmful substances enter the human body, infection and suppuration at the wound are caused, and the wound healing difficulty is increased. The timely and effective repair of the outermost skin is a very important link in the biological evolution of the living land.
At present, various medicines for promoting wound healing are available on the market, but the effects are different. The medicine applied to clinical treatment of wounds mainly plays a role in inhibiting wound infection or promoting wound healing, but few medicines with the two functions are available. For example, early topical application of phenytoin sodium is alkaline, and the pH of the wound changes during application, and this alkaline environment is not favorable to bacteria and is also highly irritating to the damaged skin, even producing a strong tingling sensation. The silver sulfadiazine which is good in healing promotion in the market is found to gradually generate drug resistance to the silver sulfadiazine along with the increase of the using time and frequency, and shows toxic and side effects and the like. It is not ideal for promoting the overall effect of wound healing.
CN201410009188.6 discloses a phenytoin derivative, phenytoin silver, a preparation method and application thereof, and the preparation has the characteristics of bacteriostasis, sterilization, inflammation diminishing, infection resistance and wound healing promotion. However, the single-prescription phenytoin-silver preparation has good curative effect, but often causes drug-induced diseases due to side effects. The Chinese and western medicine compound preparation prepared from the Chinese and western medicine can achieve the purposes of acting and coordinating, treating both symptoms and root causes, reducing toxicity and enlarging treatment symptoms. Wherein the added Chinese medicinal components of pericarpium Papaveris, Lumbricus, Notoginseng radix and Coptidis rhizoma have effects of relieving pain, promoting blood circulation for removing blood stasis, promoting granulation, astringing, clearing pathogenic fire and removing toxic substance. The invention has the advantages of wider treatment range and better curative effect of the medicine for promoting wound healing, and the treatment course is shortened, thereby reducing the dosage and lowering the cost. The application of the medicine in wound treatment has important practical significance.
Disclosure of Invention
In view of the above, the invention aims to provide a phenytoin silver compound medicine and an external preparation prepared by using the phenytoin silver compound medicine. The phenytoin silver single-prescription preparation only has the first two effects, has single treatment effect on patients with serious wound infection, and is added with a plurality of traditional Chinese medicinal materials to prepare a compound preparation, so that the treatment effect of phenytoin silver is enlarged, the medicine taking times of the patients are reduced, and the compliance of the patients is increased.
In order to achieve the purpose, the technical scheme of the invention is realized as follows:
a phenytoin-silver compound medicine comprises phenytoin-silver, poppy shell, earthworm, pseudo-ginseng and coptis, and the mass ratio of the components is (10-30): (1-3): (3-10): (4-15): (4-15); preferably, the mass ratio is 10: 1: 3: 4: 4.
an external ointment prepared from the phenytoin silver compound medicine is one of gel, oily ointment or cream;
when the gel is prepared, the gel comprises 0.1-50% of phenytoin silver compound medicine, 0.5-20% of gel matrix, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant, 0-5% of pH regulator and the balance of water by mass fraction, and the sum of the mass fractions of the components is 100%; the gel matrix comprises one or a mixture of at least two of carbomer, polyethylene glycol and gelatin; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative comprises one or a mixture of at least two of nipagin ester, sodium benzoate and benzalkonium bromide; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the pH regulator comprises one or a mixture of at least two of triethanolamine and sodium hydroxide;
when the ointment is oily ointment, the ointment comprises 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant and the balance of oily ointment matrix by mass percent, and the sum of the mass percent of the components is 100%; the oleaginous ointment matrix comprises petrolatum matrix, fat, mixed oil matrix and water-absorbing matrix; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate;
when the cream is a cream, the cream comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.1-10% of emulsifier, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant, 20-70% of oil phase substance, and the balance of water, and the sum of the mass fractions of the components is 100%; the emulsifier comprises one or a mixture of at least two of fatty acid sulfate and higher fatty acid polyol ester; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the oil phase material comprises one or a mixture of at least two of vaseline, lanolin and paraffin.
An external powder prepared from the phenytoin silver compound medicine comprises, by mass, 0.1-50% of the phenytoin silver compound medicine, 0.01-1% of an antioxidant and the balance of powder auxiliary materials, wherein the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the powder adjuvant comprises one or a mixture of at least two of starch, talcum powder and dextrin.
An external paste prepared by using the phenytoin silver compound medicine comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant, 0.01-5% of preservative and the balance of wetting agent, wherein the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the humectant comprises one or a mixture of at least two of glycerol, propylene glycol, PEG600 and PEG 1000.
An external plaster prepared by using the phenytoin silver compound medicine comprises 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant and the balance of matrix by mass percent, and the sum of the mass percent of each component is 100%; the matrix comprises vegetable oil, such as oleum Sesami, oleum Arachidis Hypogaeae, oleum Rapae, and/or oleum Verniciae Fordii; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate.
An external film agent prepared by using the phenytoin silver compound medicine comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.5-20% of film agent matrix, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant and the balance of water, wherein the sum of the mass fractions of the components is 100%; the film agent matrix comprises one or a mixture of at least two of polyvinyl alcohol, hydroxypropyl methylcellulose and polyvinylpyrrolidone; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate.
An external film coating agent prepared by using the phenytoin silver compound medicine comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.5-20% of film coating agent matrix, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant and the balance of water, wherein the sum of the mass fractions of the components is 100%; the film coating agent matrix comprises one or a mixture of more than two of polyvinyl alcohol, chitosan, carbomer, acrylic resin polyvinyl alcohol and polyvinylpyrrolidone; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative is one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate.
An external spray prepared from the phenytoin silver compound medicine comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant, 0.01-5% of preservative, 0-5% of surfactant and the balance of water, wherein the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the preservative is one or a mixture of at least two of nipagin ester and sodium benzoate; the surfactant comprises one or a mixture of at least two of sodium dodecyl benzene sulfonate, fatty glyceride, sorbitan fatty acid (span) and polysorbate (Tween).
A suspension for external use prepared by using the phenytoin silver compound medicine is divided into a powdery or granular preparation and a liquid preparation according to the existing form of the suspension;
(1) powdered or granular formulation: comprises 0.1-50% of phenytoin silver compound medicine, 29-95% of excipient, 0.05-10% of suspending agent, 0-25% of pore-forming agent, 0-12% of disintegrating agent, 0.01-1% of antioxidant, 0-12% of defoaming agent, 0-5% of surfactant and 5-35% of buffer salt by mass fraction; the excipient comprises one or more than two of sucrose, lactose and microcrystalline cellulose; the suspending agent comprises one or more of acacia, carbomer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and polyethylene glycol; the pore-forming agent comprises one or more than two of sucrose, mannitol, lactose and microcrystalline cellulose; the disintegrant comprises any one or more of croscarmellose sodium, crospovidone and sodium carboxymethyl starch; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the defoaming agent comprises one or two of silicone oil and dimeticone; the surfactant comprises any one or two of sodium dodecyl sulfate and polysorbate 80; the buffer salt comprises one or more than two of acetic acid-sodium acetate buffer salt, citric acid-trisodium citrate buffer salt and phosphate buffer salt;
(2) liquid preparation: comprises 0.1-50% phenytoin silver compound medicine, 29-95% excipient, 0.05-36.4% suspending agent, 0.01-5% preservative, 0.01-1% antioxidant and 5-35% buffer salt by mass fraction; the excipient comprises one or more than two of sucrose, lactose and microcrystalline cellulose; the suspending agent comprises one or more of acacia, carbomer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and polyethylene glycol; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the buffer salt comprises acetic acid-sodium acetate buffer salt, citric acid-trisodium citrate buffer salt, phosphate buffer salt and the like.
An external patch prepared from the phenytoin silver compound medicine comprises 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant and the balance of patch auxiliary materials by mass fraction, and the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the patch auxiliary material comprises one or a mixture of at least two of polyethylene composite membrane, ethylene-vinyl acetate copolymer and polyethylene glycol.
Wherein the phenytoin silver has antibacterial, anti-inflammatory and wound healing promoting effects. The poppy capsule and earthworm have the functions of relieving pain, promoting blood circulation to disperse blood clots, promoting granulation and astringing. The pseudo-ginseng has the obvious effects of promoting blood circulation to remove blood stasis, and relieving swelling and pain. Huang is linked with the actions of clearing heat and drying dampness, purging fire and removing toxicity. The invention ensures that the medicine for promoting wound healing has wider treatment function and better curative effect.
Compared with the prior art, the phenytoin-silver compound medicine and the external preparation prepared by using the phenytoin-silver compound medicine have the following advantages:
the phenytoin-silver compound external preparation provided by the invention has the curative effects of obviously preventing wound infection, promoting wound healing, reducing scar formation, removing necrotic tissue, promoting granulation, clearing heat, detoxicating, relieving pain and the like. Can be used for treating scald, wound ulcer, burn, and war wound. Compared with the independent application of traditional Chinese medicines and western medicines, the compound preparation takes the advantages of the traditional Chinese medicines and the western medicines to make up for the shortages and exerts respective action characteristics. Not only enlarges the treatment range, but also reduces the dosage of patients and the medication cost of the patients due to the improvement of the curative effect.
The invention expands the application range of phenytoin silver in the field of medicine, and can be prepared into various external preparations (ointment, powder, paste, plaster, film, coating agent, spray, suspension and patch), and the obtained preparation has the characteristics of definite components, quick response, stable property, low toxicity and the like.
Drawings
FIG. 1 is a diagram of the wound healing process of different administration groups of SD rat excision wound model phenytoin-silver compound gel and positive drug.
Fig. 2 is a process diagram of wound healing of different administration groups of a Guangxi Bama miniature pig excision wound model.
Fig. 3 is a graph of wound area over time for each group of the Guangxi Bama miniature pig wound model.
Fig. 4 shows the result of the bacteriostatic activity test of the phenytoin-silver compound gel.
Detailed Description
The invention is further described in detail below with reference to a specific method for preparing an external compound formulation and the verification of promoting wound healing. It is to be understood that the following examples are merely illustrative of the present invention and that these examples do not limit the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1: a gel for promoting wound healing.
The ointment for promoting wound healing comprises the following components in parts by weight:
5g of phenytoin silver, 5g of traditional Chinese medicinal materials (0.5 g of poppy shell, 1.5g of earthworm, 2g of pseudo-ginseng and 2g of coptis root), 8g of propylene glycol, 9402 g of carbomer, a proper amount of triethanolamine, 0.3g of sodium benzoate, 0.5g of sodium sulfite and a proper amount of purified water.
The preparation method comprises the following steps:
putting 2g of carbomer 940 into 70mL of purified water, after natural swelling, adding 5g of phenytoin silver, 5g of Chinese medicinal materials (0.5 g of poppy shell, 1.5g of earthworm, 2g of pseudo-ginseng and 2g of coptis chinensis), 0.3g of sodium benzoate, 8g of propylene glycol and 0.5g of sodium sulfite, dropwise adding triethanolamine after uniformly stirring to adjust the pH value to 5.5-6, adding purified water to 100g, and uniformly stirring to obtain the product.
Example 2: an ointment for promoting wound healing.
The ointment for promoting wound healing comprises the following components in parts by weight:
5g of phenytoin silver, 5g of traditional Chinese medicinal materials (0.5 g of poppy shell, 1.5g of earthworm, 2g of pseudo-ginseng and 2g of coptis root), 1g of gelatin, 5g of glycerol, 0.3g of sodium benzoate, 0.5g of sodium sulfite and a proper amount of purified water.
The preparation method comprises the following steps:
putting 1g of gelatin in 65mL of purified water, naturally swelling, adding 5g of phenytoin silver, 5g of Chinese medicinal materials (0.5 g of poppy shell, 1.5g of earthworm, 2g of pseudo-ginseng and 2g of coptis chinensis), 0.5g of sodium sulfite, 5g of glycerol and 0.3g of sodium benzoate, adding purified water to 100g, and uniformly stirring to obtain the gelatin-containing oral liquid.
Example 3: a powder for promoting wound healing.
Mixing 5g phenytoin silver (sieved with 150 mesh sieve), 5g Chinese medicinal materials (pericarpium Papaveris 0.5g, Lumbricus 1.5g, Notoginseng radix 2g and Coptidis rhizoma 2g), 0.5g sodium sulfite and 89.5g lactose.
Example 4: a paste for promoting wound healing.
Mixing 40g propylene glycol and 49.2g glycerol, heating to 85 deg.C, adding 5g phenytoin silver, 5g Chinese medicinal materials (pericarpium Papaveris 0.5g, Lumbricus 1.5g, Notoginseng radix 2g and Coptidis rhizoma 2g), 0.3g sodium benzoate and 0.5g sodium sulfite under stirring, and cooling to room temperature to obtain the final product.
Example 5: a film agent for promoting wound healing.
Taking 13g of polyvinyl alcohol, adding 65mL of purified water, stirring for swelling, then accelerating dissolution on a water bath kettle at 85 ℃, filtering, adding 5g of phenytoin silver, 5g of Chinese medicinal materials (0.5 g of poppy shell, 1.5g of earthworm, 2g of pseudo-ginseng and 2g of coptis chinensis), 8g of propylene glycol, 0.5g of sodium sulfite and 0.3g of sodium benzoate, adding purified water to 100g, stirring uniformly, coating, drying, scratching and subpackaging to obtain the traditional Chinese medicine.
Example 6: a plastics for promoting wound healing.
Adding 5g of acrylic resin-polyvinyl alcohol into 60mL of purified water, after 8h, after natural swelling, heating on a water bath kettle at 50 ℃ to accelerate dissolution, filtering, adding 5g of phenytoin silver, 5g of Chinese medicinal materials (0.5 g of poppy shell, 1.5g of earthworm, 2g of pseudo-ginseng and 2g of coptis chinensis), 5g of propylene glycol, 0.5g of sodium sulfite and 0.3g of sodium benzoate, adding purified water to 100g, and uniformly stirring to obtain the product.
Example 7: a dry suspension for promoting wound healing.
Putting 42g of microcrystalline cellulose, 25g of sodium alginate, 10g of lactose and 8g of sodium carboxymethyl starch in 400mL of water, and stirring for about 4 hours by using an electric stirrer to obtain the suspending medium. 4mL of silicone oil and 8g of sodium dodecyl sulfate are added into an emulsifier for emulsification to prepare an emulsion. Adding 5g phenytoin silver, 5g Chinese medicinal materials (plantula Papaveris 0.5g, Lumbricus 1.5g, Notoginseng radix 2g and Coptidis rhizoma 2g), 0.5g sodium sulfite, 60mL phosphate buffer salt and 40mL emulsion into suspending medium, stirring with electric stirrer, and oven drying the suspension.
Example 8: a spray for promoting wound healing.
Mixing micronized phenytoin silver 5g, Chinese medicinal materials (pericarpium Papaveris 0.5g, Lumbricus 1.5g, Notoginseng radix 2g and Coptidis rhizoma 2g) 5g and chitin 90g, and encapsulating in capsule (or eye-soaking type or bar type) 0.3g per capsule.
Example 9: a patch for promoting wound healing.
Spreading 5g of acrylic resin-polyvinyl alcohol in 60mL of purified water, standing for 8h, naturally swelling, adding 2.5g of phenytoin silver, 2.5g of Chinese medicinal materials (0.25 g of pericarpium Papaveris, 0.75g of earthworm, 1g of radix Notoginseng and 1g of rhizoma Coptidis), 0.3g of sodium benzoate and 0.5g of sodium sulfite, mixing, coating the above solution on a backing material, adhering the medicated backing material on a strip-shaped medical adhesive tape, and covering the medicated face with a medical plastic film.
Effect example 1: the phenytoin-silver compound gel has the effect on the healing of the rat wound.
Experimental animals: SD rat, female, body weight 180g-200g
Preparation and treatment of SD rat wound model compared with positive drug:
SD rats (5 rats) are injected with 10% chloral hydrate in the abdominal cavity, after anesthesia, the back hairs are shaved off, the skin is wiped with 75% ethanol, the skin is clipped with forceps and then cut with surgical scissors to reach the fascia wound, and three circular wound models with the diameter of 1cm are established. The wounds are wiped clean by normal saline, and then equivalent drug administration treatment is carried out on the wounds, so that the drugs are coated on the whole wound surface. The first wound served as a control, coated with 1% gelatin; the second wound is smeared with the phenytoin silver compound gel prepared in the first embodiment; the third wound is sprayed with chitosan antibacterial film-forming spray (positive medicine). After molding, the sterilized gauze was attached to the back of the mouse, and the mouse was raised in a single cage and administered once every 1 day. Changes of mental state, body weight, water intake, food intake, stool and urine of SD rats after administration are observed and recorded every day, and the wound healing conditions of each experimental group and the control group are photographed by a camera at the same focal distance.
The experimental results are as follows:
the chitosan antibacterial film-forming spray of the positive medicine is used for preventing and treating skin and mucosa wound infection, and has the effects of promoting wound healing, sterilizing, diminishing inflammation, reducing scar formation and the like. The drug effect of the phenytoin-silver compound preparation can be better proved by comparing with the positive medicine. As shown in figure 1, the phenytoin silver compound gel and the chitosan antibacterial film-forming spray have better wound healing effect than the control group. All wounds given the phenytoin-silver compound gel are basically completely healed on the 9 th day, new skin appears, and the wounds are not suppurative in the whole healing process. However, the wounds given positive drugs were almost healed on day 13, and some wounds were suppurative on day 4 or so. Therefore, the phenytoin silver compound gel has better effect of promoting wound healing than the positive medicine.
Effect example 2: the phenytoin-silver compound gel has the influence on the healing of the Guangxi Bama miniature fragrant pig wound.
Experimental animals: guangxi Bama miniature pig with weight of 20kg
Preparation and treatment of a Bama miniature pig wound model:
injecting appropriate amount of Lumeining into abdomen of 2 heads of Guangxi Bama miniature pig, after anesthesia, removing back hair, and cleaning skin with 75% ethanol. The skin was removed in its entire area with a scalpel, and 2 circular wound models with a diameter of 2cm were created. The wounds were wiped clean with 0.9% physiological saline and then administered separately. Randomly selecting 1 wound as a control, and filling absorbent cotton with the same amount of 1% gelatin into the wound; and (3) filling the rest 1 wound with absorbent cotton with the same amount of phenytoin-silver compound gel. The wounds were bandaged with gauze, raised in a single cage, and dosed once every 1 day. Changes of mental state, body weight, water intake, food intake, stool and urine of SD rats after administration are observed and recorded every day, and the wound healing conditions of each experimental group and the control group are photographed by a camera at the same focal distance.
The experimental results are as follows:
as the porcine skin structure is closest to the human skin structure. Therefore, the Bama miniature pig is selected as an experimental object, and whether the phenytoin silver compound gel can promote wound healing when the human skin has a wound is accurately and objectively evaluated. After 2 Guangxi Bama small fragrant pigs are modeled and administered, the healing conditions of the wounds of all groups are shown in figure 2, the wounds of the group coated with the phenytoin silver compound gel begin to scab on the 8 th day, new skin appears, the wounds heal basically on the 11 th day, and the scabs fall off on the 14 th day. While the control group began to scab on day 14 and healed substantially on day 19, the healing time was significantly delayed compared to the phenytoin silver compound gel. And most wounds of the control group appeared suppurative and red swelling on day 2. The wound coated with the phenytoin silver compound gel does not generate suppuration. According to the change of the wound area of each group with time, as shown in fig. 3, the healing rate of the wounds of the experimental group coated with the phenytoin silver compound gel is faster than that of the control group.
Effect example 3: the phenytoin-silver compound gel has the antibacterial effect.
The experimental method comprises the following steps:
(1) respectively inoculating 8 mu L of escherichia coli, staphylococcus aureus and pseudomonas aeruginosa glycerol bacteria into three 8mL liquid LB culture media, transferring the three liquid LB culture media into a small test tube, placing the small test tube into a shaking table at 37 ℃, and carrying out overnight culture at the rotating speed of 220 rpm/min;
(2) taking 200 mu L of liquid of staphylococcus aureus, escherichia coli and pseudomonas aeruginosa which are cultured overnight, diluting the liquid by 10 times, and taking 200 mu L to coat the liquid on an antibiotic-free solid LB culture medium;
(3) punching a filter paper wafer with the diameter of 1cm by using a puncher, and putting the filter paper wafer into distilled water for autoclaving;
(4) respectively placing the filter paper dipped with the sterile distilled water and the phenytoin silver compound gel into a culture plate full of staphylococcus aureus, escherichia coli and pseudomonas aeruginosa. And observing whether the inhibition zones are formed around the filter paper of the experimental group and the control group in the culture dish and the size of the inhibition zones after 24 h.
The experimental results are as follows:
the antibacterial detection result of the phenytoin silver compound gel is shown in figure 4, and in three culture plates full of staphylococcus aureus, escherichia coli and pseudomonas aeruginosa, clear and visible inhibition zones are formed around filter paper sheets stained with the phenytoin silver gel, and the phenomenon is not generated around filter paper of a control group, so that the phenytoin silver compound gel has a good antibacterial effect on the staphylococcus aureus, the escherichia coli and the pseudomonas aeruginosa.
The results show that the phenytoin-silver compound gel can obviously promote wound healing, inhibit bacterial growth, remove necrotic tissue and promote tissue regeneration.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (10)
1. The phenytoin silver compound medicine is characterized in that: comprises phenytoin silver, poppy capsule, earthworm, pseudo-ginseng and coptis, and the mass ratio of the components is (10-30): (1-3): (3-10): (4-15): (4-15); preferably, the mass ratio is 10: 1: 3: 4: 4.
2. an external ointment prepared by using the phenytoin silver compound medicine of claim 1, which is characterized in that: the topical ointment is one of gel, oily ointment or cream;
when the gel is prepared, the gel comprises 0.1-50% of phenytoin silver compound medicine, 0.5-20% of gel matrix, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant, 0-5% of pH regulator and the balance of water by mass fraction, and the sum of the mass fractions of the components is 100%; the gel matrix comprises one or a mixture of at least two of carbomer, polyethylene glycol and gelatin; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative comprises one or a mixture of at least two of nipagin ester, sodium benzoate and benzalkonium bromide; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the pH regulator comprises one or a mixture of at least two of triethanolamine and sodium hydroxide;
when the ointment is oily ointment, the ointment comprises 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant and the balance of oily ointment matrix by mass percent, and the sum of the mass percent of the components is 100%; the oleaginous ointment matrix comprises petrolatum matrix, fat, mixed oil matrix and water-absorbing matrix; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate;
when the cream is a cream, the cream comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.1-10% of emulsifier, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant, 20-70% of oil phase substance, and the balance of water, and the sum of the mass fractions of the components is 100%; the emulsifier comprises one or a mixture of at least two of fatty acid sulfate and higher fatty acid polyol ester; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the oil phase material comprises one or a mixture of at least two of vaseline, lanolin and paraffin.
3. A powder for external use prepared using the phenytoin silver complex medicine of claim 1, characterized in that: the medicine comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant and the balance of powder auxiliary materials, and the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the powder adjuvant comprises one or a mixture of at least two of starch, talcum powder and dextrin.
4. An external paste prepared using the phenytoin silver combination medicament of claim 1, wherein: the medicine comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant, 0.01-5% of preservative and the balance of wetting agent, wherein the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the humectant comprises one or a mixture of at least two of glycerol, propylene glycol, PEG600 and PEG 1000.
5. An external plaster prepared by using the phenytoin silver compound medicine as claimed in claim 1, characterized in that: the composition comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant and the balance of matrix, wherein the sum of the mass fractions of the components is 100%; the matrix comprises vegetable oil, such as oleum Sesami, oleum Arachidis Hypogaeae, oleum Rapae, and/or oleum Verniciae Fordii; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate.
6. An external film agent prepared by using the phenytoin silver compound medicine of claim 1, which is characterized in that: the composition comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.5-20% of film agent matrix, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant and the balance of water, wherein the sum of the mass fractions of the components is 100%; the film agent matrix comprises one or a mixture of at least two of polyvinyl alcohol, hydroxypropyl methylcellulose and polyvinylpyrrolidone; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate.
7. An external film coating agent prepared by using the phenytoin silver compound medicine as defined in claim 1, which is characterized in that: the composition comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.5-20% of film coating agent matrix, 1-20% of humectant, 0.01-5% of preservative, 0.01-1% of antioxidant and the balance of water, wherein the sum of the mass fractions of the components is 100%; the film coating agent matrix comprises one or a mixture of more than two of polyvinyl alcohol, chitosan, carbomer, acrylic resin polyvinyl alcohol and polyvinylpyrrolidone; the humectant comprises one or a mixture of at least two of glycerin, propylene glycol and sorbitol; the preservative is one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate.
8. An external spray prepared by using the phenytoin silver compound medicine as the claim 1, which is characterized in that: the composition comprises, by mass, 0.1-50% of phenytoin silver compound medicine, 0.01-1% of antioxidant, 0.01-5% of preservative, 0-5% of surfactant and the balance of water, wherein the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the preservative is one or a mixture of at least two of nipagin ester and sodium benzoate; the surfactant comprises one or a mixture of at least two of sodium dodecyl benzene sulfonate, fatty glyceride, sorbitan fatty acid (span) and polysorbate (Tween).
9. A suspension for external use prepared using the phenytoin silver complex pharmaceutical of claim 1, characterized in that: the suspension is divided into a powdery or granular preparation and a liquid preparation according to the existing form of the suspension;
(1) powdered or granular formulation: comprises 0.1-50% of phenytoin silver compound medicine, 29-95% of excipient, 0.05-10% of suspending agent, 0-25% of pore-forming agent, 0-12% of disintegrating agent, 0.01-1% of antioxidant, 0-12% of defoaming agent, 0-5% of surfactant and 5-35% of buffer salt by mass fraction; the excipient comprises one or more than two of sucrose, lactose and microcrystalline cellulose; the suspending agent comprises one or more of acacia, carbomer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and polyethylene glycol; the pore-forming agent comprises one or more than two of sucrose, mannitol, lactose and microcrystalline cellulose; the disintegrant comprises any one or more of croscarmellose sodium, crospovidone and sodium carboxymethyl starch; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the defoaming agent comprises one or two of silicone oil and dimeticone; the surfactant comprises any one or two of sodium dodecyl sulfate and polysorbate 80; the buffer salt comprises one or more than two of acetic acid-sodium acetate buffer salt, citric acid-trisodium citrate buffer salt and phosphate buffer salt;
(2) liquid preparation: comprises 0.1-50% phenytoin silver compound medicine, 29-95% excipient, 0.05-36.4% suspending agent, 0.01-5% preservative, 0.01-1% antioxidant and 5-35% buffer salt by mass fraction; the excipient comprises one or more than two of sucrose, lactose and microcrystalline cellulose; the suspending agent comprises one or more of acacia, carbomer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and polyethylene glycol; the preservative comprises one or a mixture of at least two of nipagin ester and sodium benzoate; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the buffer salt comprises acetic acid-sodium acetate buffer salt, citric acid-trisodium citrate buffer salt, phosphate buffer salt and the like.
10. An external patch prepared using the phenytoin silver compound medicine according to claim 1, characterized in that: the drug comprises, by mass, 0.1-50% of phenytoin silver compound drug, 0.01-1% of antioxidant and the balance of patch auxiliary materials, and the sum of the mass fractions of the components is 100%; the antioxidant comprises one or a mixture of at least two of sodium sulfite and sodium thiosulfate; the patch auxiliary material comprises one or a mixture of at least two of polyethylene composite membrane, ethylene-vinyl acetate copolymer and polyethylene glycol.
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