CN112274597A

CN112274597A - Plaster for treating open wound and preparation method thereof

Info

Publication number: CN112274597A
Application number: CN202011404159.1A
Authority: CN
Inventors: 郑兴; 姚旭
Original assignee: Nanhua University
Current assignee: Nanhua University; University of South China
Priority date: 2020-12-04
Filing date: 2020-12-04
Publication date: 2021-01-29

Abstract

The invention discloses a plaster for treating open wounds, which comprises traditional Chinese medicine powder and a cream matrix, wherein the traditional Chinese medicine powder comprises 1-20 parts of Yunnan pseudo-ginseng, 1-30 parts of angelica dahurica, 1-25 parts of pinellia ternate, 1-30 parts of rhizoma bletillae and 1-30 parts of cuttlebone; the cream matrix comprises a water phase raw material and an oil phase raw material, wherein the oil phase raw material comprises: 3-20 parts of stearic acid, 1-15 parts of white vaseline, 1-6 parts of glyceryl monostearate, 1-15 parts of liquid paraffin, 0.5-20 parts of vegetable oil and 5-20 parts of vitamin E; the water phase raw material comprises: 5-25 parts of glycerol, 0.01-1.0 part of ethylparaben, 0.10-1.0 part of triethanolamine, 0.01-1.0 part of sodium dodecyl sulfate and 20-95 parts of distilled water. The medicinal ointment has obvious effect of treating open wounds and can promote the wound contraction capacity.

Description

Plaster for treating open wound and preparation method thereof

Technical Field

The invention relates to a plaster for treating open wounds and a preparation method thereof.

Background

Open wounds, i.e. injuries in which the internal tissue of the injured part is in communication with the outside, are in short wounds in which blood can flow out, or in which muscles or bones leak out. As early as 2002, there are literature reports that worldwide costs for wound care alone are as high as $ 130- $ 150 billion annually. According to statistics, more than 1000 million people all over the world suffer from chronic wounds every year, so the external medicine has a huge market. The traditional Chinese medicine external medicine has numerous methods for treating open wounds, abundant prescription, flexible and various administration routes, definite curative effect and small toxic and side effect, and shows the characteristics and advantages of syndrome differentiation and treatment of the traditional Chinese medicine. However, since the external traditional Chinese medicine prescription mostly contains toxic medicinal materials, the external preparation containing toxic components is not allowed to be prepared by the national food and drug administration (SFDA), and the acute toxicity test, the long-term toxicity test and the teratogenesis test are required to be carried out on the external preparation containing toxic components specified in the registration of the preparations in hospitals. Therefore, although most of the traditional Chinese medicine hospitals keep a small amount of the traditional external preparation, the inheritance of the external preparation is severely restricted. The traditional external medicine of traditional Chinese medicine is gradually replaced by various dressings, and the dressings commonly used in clinic at present are various hydrocolloid dressings, alginate dressings, calcium alginate dressings, silver ion dressings, debridement glue and the like. While dressings have certain advantages in exudate management, the treatment of many wounds cannot be achieved clinically using only dressings. Therefore, the research and development of new external-use Chinese medicine drugs are imperative.

The existing patent technology, such as the externally applied traditional Chinese medicine patent ZL201010597374.8 for treating open wounds by Caojin, has the obvious effects of resisting virus and oxidation, promoting tissue cell regeneration and accelerating wound healing, can improve blood circulation of damaged areas, inhibit secondary infection of necrotic tissue bacteria and viruses, and achieve the effects of diminishing inflammation, promoting granulation and healing wounds in a short time. However, the product of the patent is powder, is inconvenient to carry, is easy to absorb moisture and stimulate, and is convenient for patients to use.

Disclosure of Invention

The invention solves the technical problem that the external application traditional Chinese medicine for treating open wounds is powder, is inconvenient to carry and is easy to absorb moisture and stimulate.

The technical scheme of the invention is that the plaster for treating the open wound comprises traditional Chinese medicine powder and a cream substrate, wherein the proportion of the traditional Chinese medicine powder to the cream substrate is (1-2) to (4-6);

the traditional Chinese medicine powder comprises, by weight, 1-20 parts of Yunnan pseudo-ginseng, 1-30 parts of angelica dahurica, 1-25 parts of pinellia ternate, 1-30 parts of rhizoma bletillae and 1-30 parts of cuttlebone;

the cream matrix comprises a water phase raw material and an oil phase raw material, wherein the oil phase raw material comprises: 8-20 parts of stearic acid, 5-15 parts of white vaseline, 1-6 parts of lanolin, 1-5 parts of liquid paraffin, 5-20 parts of vegetable oil and 5-20 parts of vitamin E; the water phase raw material comprises: 5-25 parts of glycerol, 0.01-1.0 part of ethylparaben, 0.10-1.0 part of triethanolamine, 0.01-1.0 part of sodium dodecyl sulfate and 28-95 parts of distilled water.

Preferably, the ratio of the traditional Chinese medicine powder to the cream base is 1: 3.

Experiments prove that the plaster has poor drug effect when the content of the traditional Chinese medicines is too high or too low.

Preferably, the traditional Chinese medicine powder comprises 5 parts of Yunnan pseudo-ginseng, 7 parts of angelica dahurica, 9 parts of pinellia ternate, 6 parts of rhizoma bletillae and 9 parts of cuttlebone.

Experiments prove that the ratio has the highest success rate of wound healing in one treatment course.

The invention adopts the traditional Chinese medicine powder and the cream matrix which are composed of raw materials in a specific proportion, and under the proportion, the cream matrix has a synergistic effect on the traditional Chinese medicine powder, so that the capacity of the traditional Chinese medicine powder for treating open wounds and promoting the wound contraction can be improved.

The invention also provides a preparation method of the plaster, which comprises the following steps:

s1, mixing and crushing the traditional Chinese medicine raw materials, and sieving the mixture by a sieve of 50 to 300 meshes to prepare traditional Chinese medicine powder;

s2, mixing the oil phase raw materials, heating to 75-95 ℃ to dissolve, slowly adding the oil phase raw materials into the water phase raw materials, and completely emulsifying to obtain a cream matrix;

s3, mixing the Chinese medicinal powder and cream base uniformly according to a certain proportion.

Preferably, in step S2, the oil phase raw materials are mixed and heated to 85 ℃ for dissolution.

The temperature is too low, the raw materials are not fully dissolved, the temperature is too high, key components in the important components can go bad, and the drug effect is influenced.

The invention is further explained below:

pharmacological analysis of the drug of the invention: radix angelicae: pungent and warm with the actions of dispelling wind, dispersing dampness, draining pus, promoting generation of vital energy and alleviating pain. The bleeding time, the blood coagulation time and the prothrombin generation time of animals are obviously shortened when the angelica dahurica is extracted. The enzyme soluble component has dilating effect on peripheral blood vessel and has obvious analgesic effect. It has inhibitory effect on various bacteria, Escherichia coli, Shigella sonnei, typhoid bacillus, paratyphoid bacillus, and Vibrio cholerae.

And (3) common bletilla pseudobulb: bitter, sweet and cool, has the functions of tonifying lung, stopping bleeding, relieving swelling and promoting tissue regeneration. In the hemostasis experiment, rhizoma bletillae water extract can cover most of the liver lobes and spleens of the dogs which are cut off and can adhere to the dogs by itself, so that bleeding stops immediately. After the rhizoma bletillae liquid is injected into the blood circulation of frogs, the blood cells in the non-tip blood vessels can be coagulated. The methanol extract of rhizoma Bletillae has antibacterial activity against Staphylococcus aureus and Staphylococcus aureus, and has obvious analgesic and anti-infectious effects on wound of burn patient, and has the advantage of rapid scabbing.

And (3) sea squirt shell: salty, astringent and slightly warm, it has the actions of astringing to stop bleeding and relieving hyperacidity. Experiments show that the cuttlebone powder preparation has healing effect on chronic experimental gastric ulcer of rats caused by acetic acid. The water decoction has hemostatic effect on metrorrhagia, digestive tract hemorrhage, pulmonary tuberculosis hemoptysis.

Yunnan pseudo-ginseng: sweet and slight tongue, has the functions of promoting blood circulation to remove blood stasis, stopping bleeding, relieving swelling and alleviating pain. It can be used for treating hemorrhage and traumatic injury. Contains a special amino acid with hemostatic activity, namely heptanine. It also has the functions of exciting the middle-jiao nerve system, improving mental and physical activities, resisting fatigue and ulcer, tranquilizing, hypnotizing, shortening rabbit blood coagulation time, resisting heparin anticoagulation, and inducing platelet to release hemostatic active substance (dencichine).

Pinellia ternata: pungent and warm with toxicity, it has the actions of drying dampness and resolving phlegm, checking adverse rise of qi and arresting vomiting. Unprocessed has the action of treating furuncle.

Ethyl paraben: can inhibit the activity of respiratory enzyme system and transfer enzyme system of microbial cell and destroy the cell membrane mechanism of microbe, so that it has wide antibacterial effect on mildew, yeast and bacteria.

Triethanolamine: through the infiltration and the capillary action principle, play the dual function of cleaning and drainage.

The invention discloses a medicinal ointment for treating open wounds. The medicinal ointment has the following advantages:

1. the medicinal paste is convenient to use; uniform and fine texture, good stability, and no irritation to skin.

2. The adjuvant in the medicinal paste has effect in promoting Chinese medicinal components.

3. The medicinal ointment has anti-inflammatory and anti-infection effects, and can be used for treating open wound with obvious effect and promoting wound contraction.

Drawings

Fig. 1 shows the physiological condition of the wound surface after molding.

Fig. 2 is a comparison of wound healing time.

Fig. 3 is a comparison of wound healing areas.

Detailed Description

Example 1

Screening of Chinese medicine composition

According to the mass parts, the Yunnan pseudo-ginseng, the dahurian angelica root, the pinellia tuber, the bletilla striata and the cuttlebone are respectively mixed according to the design proportion in the table 1, smashed and sieved by a 200-mesh sieve to prepare the traditional Chinese medicine powder with 7 proportions for later use. For patients with wound area less than 5cm X2 cm (such as knife wound, severe wound, etc.), the 7 kinds of Chinese medicinal powder are randomly used after debridement, and each person only uses once to observe the healing degree of 13d wound. Through data statistics for more than one year, the number of people who can cure the wound with one medication is shown in table 1:

TABLE 1 number of people who can cure wounds with one-time application of each prescription

As can be seen from the above table, the Chinese medicinal powder prepared by mixing 5 parts of Yunnan pseudo-ginseng, 7 parts of angelica dahurica, 9 parts of pinellia ternate, 6 parts of rhizoma bletillae and 9 parts of cuttlebone, crushing and sieving with a 200-mesh sieve has a cure rate of up to 90% after one-time use, so that the prescription No. 3 is selected as the Chinese medicinal powder in the following examples.

Example 2

Design dose group

3 different dosage groups (shown in table 2) are set according to the addition amount of the traditional Chinese medicine powder, the appearance and the properties are re-evaluated, a drug effect test is carried out, and the optimal proportion is screened according to the result.

TABLE 2 compositions of the respective parts

Note: high dose group: medicinal powder and cream matrix 1:1

The medium dose group: medicinal powder and cream matrix 1:3

Low dose group: medicinal powder and cream matrix 1:6

The three groups of plaster raw materials are prepared into plaster, and the specific operation steps comprise the following steps:

s1, mixing 5 parts of Yunnan pseudo-ginseng, 7 parts of angelica dahurica, 9 parts of pinellia ternate, 6 parts of rhizoma bletillae and 9 parts of cuttlebone, crushing, and sieving with a 200-mesh sieve to obtain traditional Chinese medicine powder;

s2, mixing the oil phase raw materials in the table 1, heating to 85 ℃ for dissolution, slowly adding the mixture into the water phase raw materials in the table 2, and completely emulsifying to obtain a cream matrix;

s3, mixing the Chinese medicinal powder and cream matrix uniformly according to the three proportions to obtain three batches of ointments.

Example 3

Quality detection

The 3 ointment samples of example 1 were examined under the terms of ointment cream (general rule 0109) and rinse (general rule 0128) in the fourth part of the pharmacopoeia 2015 edition, and the results showed that the quality of the three samples was acceptable. The specific operation is as follows:

1) appearance property: 3 batches of samples were taken, and the color, uniformity, fineness and ease of smearing were visually observed.

2) The difference of the loading amount: the inspection is carried out according to the minimum loading inspection method of 0942 in the four general rules of the pharmacopoeia 2015 edition, which is in accordance with the regulations.

3) Granularity: according to 0982 particle size and particle size distribution determination method in the four-part general rule of Chinese pharmacopoeia 2015 edition, particles larger than 180 μm are not detected.

4) And (3) sterilization: the bacteria are checked according to the sterility test method 1101 of the four general rules of Chinese pharmacopoeia 2015 edition, and viable bacteria cannot be checked.

5) No heat source: the inspection is carried out according to the heat source inspection method 1142 of the general rules of the four parts of the pharmacopoeia 2015 edition, which is in accordance with the regulations.

6) pH value: the pH value should be 5.5-7.0 according to the method of 0631pH value determination of the four-part general rules of Chinese pharmacopoeia 2015 edition.

7) Heavy metals: the color of the test sample is not darker than that of the reference substance by the second method of the 0821 heavy metal inspection method according to the general rules of the four parts of the pharmacopoeia 2015 edition.

8) Arsenic salt: compared with the standard arsenic spot, the color of the product is not darker according to the first method of the 0822 arsenic salt inspection method of the four-part general rules of the Chinese pharmacopoeia 2015 edition.

Example 4

And (3) stability investigation: experimental research shows that the three batches of the medicinal ointment are stable and meet the requirements of Chinese pharmacopoeia 2015 edition. The specific operation is as follows:

1) and (3) centrifugal experiment: weighing 2g of ointment of 3 batches respectively, placing in a centrifuge tube, and centrifuging at 4000r/min for 30min to observe whether oil-water demixing demulsification occurs.

2) Heat resistance: respectively taking appropriate amount of the prepared three batches of ointments, sealing in a plastic bottle, placing in an oven at 60 + -2 deg.C, taking out after 0.5h, returning to room temperature, and observing appearance, color and ductility changes of the ointments.

3) Cold resistance: respectively taking appropriate amount of the prepared three batches of ointments, sealing in a plastic bottle, placing in a refrigerator at-5 + -2 deg.C, taking out after 12h, returning to room temperature, and observing appearance, color and ductility changes of the ointments.

The concrete result is as follows: from the appearance, centrifugal stability, and pH examination results (table 3), it was found that: the cream is fine and uniform, has centrifugal stability, and has pH value reaching pharmacopeia standard.

TABLE 3 appearance Properties of the three batches of ointments

As can be seen from the results of the extensibility of the cream (Table 4) and the cold and heat resistance of the cream (Table 5), the cream was qualified in both the extensibility and cold and heat resistance tests.

TABLE 4 ductility results for three ointment batches

Note: three measurements were taken for each prescription and,

the average values of d1, d2 and d 3.

TABLE 5 Cold and Heat stability results for three ointments

Note: "-" indicates no change in color, particle size and uniformity, and "+" and "-" in ductility represent an increase and decrease in diameter, respectively.

Example 5

Skin irritation test: experimental research shows that the three batches of medicinal ointments have no irritation, and meet the requirements of Chinese pharmacopoeia 2015 edition. The specific operation is as follows:

32 rats with the weight of 250-300g are taken, the abdomen of the rat is sheared 24h before the tested medicine is given, the area is about 3cm multiplied by 3cm, and whether the dehaired skin is injured or not is checked 24h after dehairing, for example, the injured skin cannot be used for a complete skin irritation experiment. The damaged skin is prepared by removing hair with sand paper to remove blood. During the experiment, rats are randomly divided into 4 groups when testing a batch of ointment, wherein the group A is used for a complete skin irritation experiment, the group B is used for a damaged skin irritation experiment, the group C is a blank control group, and the group D is a positive drug control group.

For example, the results of the skin irritation test for the dose groups in the test ointment are shown in table 6:

TABLE 6 test results of multiple rabbit irritativeness of test substances

Example 6

Pharmacodynamic experiment

The specific experimental process is as follows:

1.1 preparation of skin wounds: 18 rabbits with about 2.5kg male and female are divided into A, B, C3 big groups, each group is 6, the rabbits in group A are marked as A1, A2, A3, A4, A5 and A6, the experimental design of group B and group C is identical to that of group A, and the experimental design of group B and group C is marked as B1, B2, B3, B4, B5, B6, C1, C2, C3, C4, C5 and C6. Fasting was carried out for 12h before the experiment, and anesthesia was carried out by intravenous injection into the ear margin with a 3% sodium pentobarbital solution at a concentration of 1 mL/kg. The hair on the back was cut short and depilated with a razor with a depilatory area of about 8cm by 10 cm. After the complex iodine is disinfected, 4 circular wound surfaces with the diameter of 1.5cm are respectively prepared on the two sides of the back spine and at the position 3cm away from the back wound surface on the same side from front to back, wherein the left wound surface is 1 cm, the left wound surface is 2cm, and the right wound surface is 1 cm. Marking the depilated part along a skin punch with diameter of 1.5cm with a skin marking pen, lifting the skin with tweezers, cutting off the whole skin layer according to the marked position and size with an ophthalmic scissors, and forming a wound model with whole skin defect by slight bleeding.

1.2 experimental grouping: four wounds on the back of the rabbit are set into different experimental groups, for example, the left 1 of the group A of rabbits is a positive control group (mupirocin), the left 2 is a cream high-dose group, the right 1 is a cream medium-dose group, and the right 2 is a cream low-dose group; the group B rabbits comprise a left 1 Chinese medicinal powder group, a left 2 blank group (cream matrix), a right 1 positive control group (mupirocin), and a right 2 cream high dose group; the rabbit of group C has a left 1 cream middle dose group, a left 2 cream low dose group, a right 1 traditional Chinese medicine powder group, and a right 2 blank group. After grouping, the male and female parts of three groups ABC are guaranteed. On each wound, 0.300g of cream matrix is coated on a blank group, 0.043g of powder is coated on a traditional Chinese medicine powder group (according to the conversion table of body surface area proportion and dose of common experimental animals and human, a patient with the weight of 70kg wound of 5cm multiplied by 2cm is clinically administered 0.366g of powder each time, then 1.5kg of rabbit coated powder should be 0.366g/14.2 ═ 0.0258g, and 2.5kg of rabbit coated 0.043g of powder), 0.129g of high-dose, medium-dose and low-dose group cream is respectively coated on a cream high-dose group, 0.300g of mupirocin cream (clinical theoretical dose) is coated on a positive group, 6 rabbits are shared in each experimental group, and 4 wounds exist on each rabbit, and the wounds are marked by picric acid.

All wounds are covered with vaseline oil gauze after being applied with the medicine, then bandaged with sterilized medical gauze, and fixed by an elastic bandage to prevent rabbits from licking the wounds. Meanwhile, the wound is disinfected by complex iodine every day and then is treated by the original method for dressing change, and the dressing change is carried out once every day until the experiment is finished. Observing each index for 18 days. Each rabbit was raised in cages. Rabbits were sacrificed on day 19 of the experiment.

5.3 rabbit wound healing

After modeling, a wound group is randomly selected from a positive control group, a cream high-dose group, a cream medium-dose group, a cream low-dose group, a powder group and a cream matrix group as a wound surface visual observation object (as shown in figure 1).

The results show that: as can be seen from figure 1, in the initial stage of the healing of the rabbit wound, the wound surface is slightly bleeding, red and swollen, and a small amount of exudate exists; in the middle stage, the edge of the wound surface begins to shrink, the wound surface is reduced, scabs are increased and thickened, and part of the wound surface is red and swollen; when the experiment is carried out to the later stage, most scabs of the wound surface begin to fall off, the wound is more obviously healed, new villi is generated on the edge of part of the wound surface, new flesh grows out, and a small amount of pigmentation is formed on the other part of the wound surface; the experiment was carried out to 13d, with most of the wounds completely healed, and experiment 19d with almost all wounds healed.

The average time to wound healing on the backs of rabbits was plotted (as shown in fig. 2). The wound healing time of the cream-in-dose group was only 11.2d, shorter than 12d of the positive control group, and much shorter than 13.2d of the cream-in-dose group and 13.75d of the powder group. The amount of the Chinese medicinal powder actually applied to the wound in the dose group in the cream is actually less than that in the powder group, but the effect of promoting the wound healing is obviously better than that in the powder group. This indicates that the powder is changed into cream form, which promotes the exertion of the effect of the traditional Chinese medicine powder. This is an effect that is difficult to predict. The healing time of the cream base group is longest, the time of the cream high dose group is longer than that of the cream medium dose group, and therefore, the optimal proportion of the cream base and the traditional Chinese medicine powder required by the preparation of the cream and the wound healing is required.

The area of wound healing at different stages (original wound area-unhealed wound area on the day) was recorded and compared analytically (fig. 3). The trend of the wound healing area presentation of each group is found in the figure, wherein the cream heals the fastest and the best effect is obtained in the medium dosage group. And the low dose group, the positive control group and the high dose group, wherein the using amount of the cream in the medium dose group is 0.129g, namely 0.03225g of the traditional Chinese medicine powder is used, and 0.09675g of cream matrix is used, and the amount of the traditional Chinese medicine powder in the medium dose group is 75% of that in the traditional Chinese medicine powder group. However, the effect is far better than that of the traditional Chinese medicine powder group. The powder is changed into a cream form, so that the effect of the traditional Chinese medicine powder is promoted, and the wound healing area in the same period is greatly increased.

While particular embodiments of the present invention have been illustrated and described, it would be obvious that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.

Claims

1. A plaster for treating open wounds is characterized by comprising traditional Chinese medicine powder and a cream matrix, wherein the proportion of the traditional Chinese medicine powder to the cream matrix is (1-2) to (4-6);

the traditional Chinese medicine powder comprises, by weight, 1-20 parts of Yunnan pseudo-ginseng, 1-30 parts of angelica dahurica, 1-25 parts of pinellia ternate, 1-30 parts of rhizoma bletillae and 1-30 parts of cuttlebone; the cream matrix comprises a water phase raw material and an oil phase raw material, wherein the oil phase raw material comprises: 3-20 parts of stearic acid, 1-15 parts of white vaseline, 1-6 parts of glyceryl monostearate, 1-15 parts of liquid paraffin, 0.5-20 parts of vegetable oil and 5-20 parts of vitamin E; the water phase raw material comprises: 5-25 parts of glycerol, 0.01-1.0 part of ethylparaben, 0.10-1.0 part of triethanolamine, 0.01-1.0 part of sodium dodecyl sulfate and 20-95 parts of distilled water.

2. A plaster for the treatment of an open wound according to claim 1, wherein the ratio of the traditional Chinese medicine powder to the cream base is 1: 3.

3. The plaster for treating open wounds as claimed in claim 1, wherein the Chinese medicinal powder comprises 5 parts of Yunnan pseudo-ginseng, 7 parts of angelica dahurica, 9 parts of pinellia ternate, 6 parts of bletilla striata and 9 parts of cuttlebone.

4. A process for the preparation of a plaster for the treatment of open wounds according to any one of claims 1 to 3, comprising the steps of:

mixing the oil phase raw materials, heating to 75-95 deg.C for dissolving, slowly adding into the water phase raw materials, and emulsifying completely to obtain cream matrix;

s2, mixing the Chinese medicinal powder and cream base uniformly according to a certain proportion.

5. The method according to claim 4, wherein in step S1, the oil phase raw materials are mixed and heated to 85 ℃ to be dissolved.