阅读说明：本技术 一种苯妥英银复方药物及使用其制备的外用制剂 (Phenytoin-silver compound medicine and external preparation prepared by using same ) 是由 周红刚 张�杰 杨新意 陈立营 杨光 艾笑羽 李霄鹤 毕谆 肖婷 于 2019-12-19 设计创作，主要内容包括：本发明提供了一种苯妥英银复方药物及使用其制备的外用制剂,该复方药物,包括苯妥英银、罂粟壳、地龙、三七及黄连,且以上各组分的质量比为(10-30)：(1-3)：(3-10)：(4-15)：(4-15)。本发明使得促伤口愈合这类药物的治疗功能更广,疗效更佳。本发明扩大了苯妥英银外用复方制剂剂型的种类,所得复方制剂具有成分相对明确、起效迅速、质量可控、低毒等优点。(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.)

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.

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.