Alkannin preparation for bacteriostasis and cleaning and preparation method thereof

Abstract

The invention belongs to the technical field of bacteriostasis, and provides an alkannin preparation which is prepared from the following raw materials in parts by weight: 1-5 parts of lithospermum extract, 1-5 parts of pungent litse fruit alcohol extract and 10-150 parts of auxiliary materials. The alkannin preparation provided by the invention has an obvious antibacterial effect on various germs, has good functions of resisting inflammation, resisting oxidation and promoting wound healing, can obtain a good synergistic antibacterial cleaning effect by simultaneously adopting the lithospermum extract and the litsea cubeba alcohol extract according to a proper proportion and a proper preparation method, and has the advantages of no side effect and no toxic or side effect. The traditional Chinese medicine has a good curative effect on infectious skin diseases.

Description

Technical Field

[0001] The invention belongs to the technical field of antibacterial treatment, and particularly relates to a shikonin preparation for antibacterial cleaning and a preparation method thereof. Background Art

[0002] Military combat exercises are conducted in harsh and limited environments, particularly in the humid jungle environment, which fosters the growth of bacteria and fungi, significantly impacting soldiers' combat effectiveness. Furthermore, skin diseases, particularly fungal infections, are prevalent during military training. Currently, commonly used cleaning and disinfecting wipes are bulky and heavy, making them difficult to carry and limiting their use. Consequently, a portable, effective, and specialized antibacterial agent is currently lacking for the challenging conditions of military combat exercises. Summary of the Invention

[0003] In order to solve the above problems existing in the prior art, the present invention provides a shikonin preparation for antibacterial cleaning and a preparation method thereof.

[0004] A shikonin preparation is prepared from the following raw materials in parts by weight: 1-5 parts by weight of lithospermum erythrorhizon extract, 1-5 parts by weight of litsea cubeba ethanol extract, and 10-150 parts by weight of auxiliary materials.

[0005] The present invention has the following beneficial effects:

[0006] 1. The lithospermum extract of the present invention has antibacterial, anti-inflammatory, antioxidant and wound healing functions, and the alcohol extract of Litsea cubeba has antioxidant and antibacterial functions. The simultaneous use of the two has a good antibacterial and cleaning effect and has a good therapeutic effect on infectious skin diseases.

[0007] 2. When the dosage form of the present invention is an effervescent tablet, it can improve water quality and adjust pH value; the effervescent tablet can concentrate the active ingredients and is easy to carry and transport.

[0008] 3. When the dosage form of the present invention is an effervescent tablet, the lithospermum officinale extract, the litsea cubeba ethanol extract and related excipients are scientifically proportioned, freeze-dried and dehumidified, stirred and mixed, and tableted. The obtained effervescent tablet has good tablet shape, high hardness, does not stick to the punch, has intense bubbles and good disintegration effect.

[0009] 4. The reasonable proportions and synergistic effects of the various components of the present invention jointly enhance the antibacterial and anti-inflammatory effects; the various steps and parameters of the preparation method are closely coordinated and synergistic, thereby enhancing the efficacy of the product.

[0010] 5. The present invention can achieve dual supplementation in preventing and treating fungal infectious skin diseases for soldiers, and at the same time play a protective role for inevitable wounds in field combat exercises, effectively solving the problem that conventional drugs are not suitable for harsh conditions. DETAILED DESCRIPTION

[0011] To make the technical solutions, objectives and advantages of the present invention more clear, the present invention is further described in detail below through specific embodiments. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention.

[0012] In the present invention, the mass-to-volume ratio (w:v, or solid-to-liquid ratio) is the ratio of the weight of the solid (g) to the volume of the liquid (mL). For example, the ratio of the mass (g) of lithospermum root to the volume (mL) of a 95% ethanol solution is: for example, if 100g of lithospermum root is added to 1000mL of 95% ethanol solution, the mass-to-volume ratio of lithospermum to 95% ethanol solution is 1:10.

[0013] The present invention provides a shikonin preparation for antibacterial cleaning, which is prepared by containing the following raw materials in parts by weight:

[0014] 1-5 parts by weight of Lithospermum officinale extract, 1-5 parts by weight of Litsea cubeba ethanol extract, and 10-150 parts by weight of auxiliary materials.

[0015] Specifically, the preparation is made from the following raw materials in parts by weight:

[0016] The amount of lithospermum erythrorhizon extract is 1 to 5 parts by weight, for example, any one of 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 parts by weight, or a range between two of them, for example, any one of 2 to 3 parts by weight, 1.5 to 3.5 parts by weight, 1 to 4 parts by weight, 2 to 4.5 parts by weight, and 3 to 5 parts by weight, preferably 2.5 parts by weight.

[0017] The alcohol extract of Litsea cubeba is 1 to 5 parts by weight, for example, any one of 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 parts by weight, or a range between two of them, for example, any one of 2 to 3 parts by weight, 1.5 to 3.5 parts by weight, 1 to 4 parts by weight, 2 to 4.5 parts by weight, and 3 to 5 parts by weight, preferably 2.5 parts by weight.

[0018] The auxiliary material is 10 to 150 parts by weight, for example, any one of 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, and 150 parts by weight, or a range between two thereof, for example, any one of 90 to 100 parts by weight, 80 to 110 parts by weight, 10 to 120 parts by weight, 60 to 130 parts by weight, 50 to 140 parts by weight, 40 to 150 parts by weight, and 85 to 115 parts by weight, and preferably 95 parts by weight.

[0019] In a preferred embodiment, the preparation is made from the following raw materials in parts by weight:

[0020] 1-4 parts by weight of Lithospermum officinale extract, 1-4 parts by weight of Litsea cubeba ethanol extract, and 92-98 parts by weight of auxiliary materials.

[0021] In a preferred embodiment, the preparation is made from the following raw materials in parts by weight:

[0022] 2-3 parts by weight of Lithospermum officinale extract, 2-3 parts by weight of Litsea cubeba ethanol extract, and 94-96 parts by weight of auxiliary materials.

[0023] In a preferred embodiment, the preparation is made from the following raw materials in parts by weight:

[0024] 2.5 parts by weight of Lithospermum officinale extract, 2.5 parts by weight of Litsea cubeba ethanol extract, and 95 parts by weight of auxiliary materials.

[0025] The lithospermum extract is extracted from the root of Lithospermum officinale. Lithospermum officinale is preferably produced in the Xinjiang Uygur Autonomous Region. The Litsea cubeba ethanol extract is extracted from the fruit of Litsea cubeba. Litsea cubeba is preferably produced in Lincang, Yunnan Province. The quality of both Lithospermum officinale and Litsea cubeba meets the requirements of the Chinese Pharmacopoeia.

[0026] In a preferred embodiment, the preparation method of the above-mentioned Lithospermum officinale extract comprises the following steps:

[0027] S1: Soak the roots of Lithospermum officinale in 95% (volume fraction) ethanol solution for 1 to 4 hours (preferably 3 hours), with the mass volume ratio (solid-liquid ratio) of the two being 1: (5 to 10), preferably 1:5 or 1:10, and more preferably 1:5.

[0028] S2: Then heat in a water bath at 50-80°C (preferably 60°C) for 2-4 h (preferably 3 h).

[0029] S3: filtration for the first time to obtain the first filter residue and the first filtrate of Lithospermum officinale.

[0030] S4: adding 95% ethanol solution to the first filter residue of Lithospermum officinale, with the mass volume ratio (solid-liquid ratio) of the two being 1:(5-10), preferably 1:5 or 1:10, more preferably 1:5.

[0031] S5: Heat in a water bath at 50-80°C (preferably 60°C) for 2-4 h (preferably 3 h).

[0032] S6: Filter for the second time to obtain the second filtrate of Lithospermum officinale.

[0033] S7: combining the first filtrate of Lithospermum erythrorhizon and the second filtrate of Lithospermum erythrorhizon to obtain a total filtrate of Lithospermum erythrorhizon;

[0034] S8: Add 2% sodium hydroxide solution to the total filtrate of Lithospermum officinale to adjust the pH to 10.5-11.5 (preferably 11.0), and then adjust the pH to 1.5-2.5 (preferably 2.0) with hydrochloric acid to obtain Lithospermum officinale concentrate;

[0035] S9: Concentrating the above-mentioned Lithospermum officinale concentrate under reduced pressure to 1 / 10 to 1 / 5 of the original volume, preferably 1 / 10, to obtain Lithospermum officinale extract;

[0036] S10: Drying the lithospermum erythrorhizon extract to a constant weight to obtain a lithospermum erythrorhizon extract; the drying temperature is 40 to 60° C. (preferably 50° C.) and the drying time is 1 to 4 hours, preferably 2 hours.

[0037] In a preferred embodiment, the preparation method of the above-mentioned Litsea cubeba ethanol extract comprises the following steps:

[0038] S1: drying fresh Litsea cubeba fruit naturally at room temperature (preferably in the sun for 10 days), and then drying;

[0039] S2: Grinding the mixture into 30-50 mesh (preferably 40 mesh) to obtain Litsea cubeba powder;

[0040] S3: adding 95% ethanol solution to the Litsea cubeba powder, with a mass volume ratio (solid-liquid ratio) of 1:(5-15), preferably 1:5 or 1:10, more preferably 1:10;

[0041] S4: then soaking at 20-40°C (preferably 30°C) for 1-3 hours (preferably 2 hours);

[0042] S5: filtering for the first time to obtain the first filtrate of Litsea cubeba and the first filtrate residue of Litsea cubeba;

[0043] S6: adding 100% ethanol or 95% ethanol solution to the first filter residue of Litsea cubeba, with the mass volume ratio (solid-liquid ratio) of the two being 1:(5-10), preferably 1:5 or 1:10, more preferably 1:10;

[0044] S7: Soak at 20-40°C (preferably 30°C) for 1-4 hours (preferably 3 hours);

[0045] S8: Filter again for the second time to obtain the second filtrate of Litsea cubeba;

[0046] S9: combining the first filtrate of Litsea cubeba and the second filtrate of Litsea cubeba to obtain a total filtrate of Litsea cubeba;

[0047] S10: Concentrating the total filtrate of Litsea cubeba under reduced pressure to 1 / 10 to 1 / 5 of the original volume, more preferably to 1 / 10, to obtain Litsea cubeba extract;

[0048] S11: Drying the Litsea cubeba extract to a constant weight to obtain Litsea cubeba ethanol extract, wherein the drying temperature is 40-60° C. (preferably 50° C.) and the drying time is 1-4 h, preferably 2 h.

[0049] The above-mentioned Lithospermum officinale extract and Litsea cubeba ethanol extract can also be commercially available products, such as those with shikonin content of more than 99%.

[0050] The extraction method of the lithospermum erythrorhizon extract adopts ethanol extraction. Compared with existing technologies such as solvent extraction, vacuum distillation, ultrasonic extraction, microwave extraction, and supercritical extraction, it can increase the content of shikonin in the extract while reducing the content of impurities in the extract. The above extraction method performs "acid extraction and alkali precipitation" (i.e., adjusting the pH value to 1.5-2.5) on the total lithospermum erythrorhizon filtrate before vacuum concentration, which can effectively save the amount of organic solvent, reduce costs, and reduce environmental pollution. The above extraction method can make the prepared shikonin higher in purity, with significantly fewer impurities than other preparation methods, and the highest yield.

[0051] The above-mentioned litsea cubeba ethanol extract is extracted with ethanol, and the obtained litsea cubeba ethanol extract has strong antibacterial activity.

[0052] In a preferred embodiment, the dosage form of the above preparation can be tablets, granules, or powders, preferably effervescent tablets.

[0053] When the dosage form of the above preparation is an effervescent tablet, the above excipients include:

[0054] 2 to 6 parts by weight of cosolvent, 30 to 50 parts by weight of filler, 20 to 30 parts by weight of alkali source, 15 to 25 parts by weight of acid source, and 5 to 10 parts by weight of lubricant.

[0055] In a preferred embodiment:

[0056] The above-mentioned cosolvent can be a pharmaceutical cosolvent such as inorganic compounds (such as potassium iodide, etc.), organic acids and their salts (such as benzoic acid, etc.), amide or amine compounds (such as ethylenediamine, etc.), water-soluble polymer compounds (such as polyvinyl pyrrolidone, polyethylene glycol, etc.); the above-mentioned cosolvent is preferably polyvinyl pyrrolidone (PVP), such as PVP-k15, PVP-k30, and more preferably PVP-k30.

[0057] The filler can be a pharmaceutical filler such as mannitol, starch, powdered sugar, dextrin, lactose, microcrystalline cellulose, etc., preferably mannitol.

[0058] The lubricant can be pharmaceutical lubricants such as hydroxypropyl methylcellulose, glyceryl distearate, polyethylene glycol (PEG, such as PEG6000, PEG4000, etc.), preferably PEG6000.

[0059] The above acid source can be pharmaceutical acid sources such as citric acid, tartaric acid, fumaric acid, adipic acid, PEG polyethylene glycol, malic acid, water-soluble amino acids, dilute mineral acids (such as dilute hydrochloric acid), acid salts (potassium dihydrogen citrate, potassium hydrogen tartrate, sodium fumarate, etc.), preferably citric acid.

[0060] The above-mentioned alkali source can be a pharmaceutical alkali source such as sodium bicarbonate, sodium carbonate, potassium carbonate, etc., preferably sodium bicarbonate.

[0061] The present invention also provides a method for preparing a shikonin preparation for antibacterial cleaning, comprising the following steps: mixing the lithospermum officinale extract, the litsea cubeba ethanol extract, and auxiliary materials to obtain the preparation.

[0062] In a preferred embodiment, when the dosage form of the preparation is an effervescent tablet, the preparation method comprises the following steps:

[0063] Screening: The above-mentioned lithospermum erythrorhizon extract, litsea cubeba ethanol extract, cosolvent, filler, lubricant, acid source and alkali source are screened separately; the screening process uses a 40-80 mesh (preferably 60 mesh) sieve.

[0064] Drying: Dry the sieved Lithospermum officinale extract, Litsea cubeba alcohol extract, cosolvent, filler, lubricant, acid source, and alkali source to constant weight; the drying time can be 2 to 6 hours, preferably 4 hours, and the drying temperature is 100 to 120°C, preferably 105°C.

[0065] First mixing: evenly mix the dried Lithospermum officinale extract, Litsea cubeba ethanol extract, filler, cosolvent and acid source to obtain a first mixed material.

[0066] Second mixing: mix the alkali source and the first mixture to obtain the second mixture.

[0067] Third mixing: Mix the lubricant and the second mixture to obtain the third mixture.

[0068] Tableting: The third mixed material is tableted to obtain effervescent tablets.

[0069] The mass of the effervescent tablets is 0.585±0.04 g per tablet.

[0070] When in use, 300 to 800 mL (preferably 500 mL) of water is added to each effervescent tablet to obtain a solution for disinfection and antibacterial treatment.

[0071] The above preparation method abandons the traditional wet granulation tableting method and directly tablets the powdered third mixture. Because the effervescent process of the effervescent tablet is a chemical reaction between the acid source and the alkali source in the raw materials, the effervescent tablet needs to avoid uncontrolled contact with moisture during the production process to avoid affecting the effervescent effect. The third mixture is directly tableted without granulation, which saves process time and has high production efficiency; it can also avoid contact between the raw materials and moisture, and avoid heating during the granulation and drying process, which can effectively retain the effective ingredients of the two traditional Chinese medicine extracts. As a skin contact drug, the effervescent tablet does not require any liquid adhesive during the preparation process, and at the same time abandons the use of traditional liquid co-solvents, avoiding the risk of solvent residues to the human body and saving costs.

[0072] Lithospermum erythrorhizon Siebold & Zucc. is a plant of the genus Lithospermum in the Boraginaceae family. It has anti-inflammatory, antiviral, antibacterial, antioxidant, tumor-suppressing, anti-fertility, and immune-regulating effects.

[0073] Litsea pungens Hemsl. is a deciduous small tree of the genus Litsea in the Lauraceae family. It has the functions of anti-oxidation and inhibiting the reproduction of harmful microorganisms.

[0074] Unless otherwise specified, the various reagents, materials, etc. used in the following examples are all products that can be obtained from commercial channels; unless otherwise specified, the various tests and detection methods used in the following examples are all conventional tests and detection methods in the field, which can be obtained from textbooks, reference books or academic journals.

[0075] Example 1

[0076] This example is used to illustrate the ingredient ratio and preparation method of a shikonin preparation for antibacterial cleaning in the form of an effervescent tablet.

[0077] The raw materials of the Lithospermum officinale effervescent tablets of the present embodiment contain:

[0078] Lithospermum officinale extract 2.5g, Litsea cubeba alcohol extract 2.5g, PVP-k30 4g, mannitol 40g, sodium bicarbonate 25g, citric acid 20g, PEG6000 6g.

[0079] The preparation method of the above-mentioned Lithospermum officinale effervescent tablet comprises the following steps:

[0080] S1: Preparation of Lithospermum officinale extract:

[0081] (1) Weigh the roots of Lithospermum officinale in a round-bottom flask and soak them in 95% ethanol solution for 2 h; the mass-to-volume ratio of Lithospermum officinale roots to 95% ethanol solution is 1:5.

[0082] (2) Heat in a water bath at 60°C for 3 h.

[0083] (3) Filtration for the first time to obtain the first filter residue and the first filtrate of Lithospermum erythrorhizon; the first filtrate of Lithospermum erythrorhizon is stored separately for later use.

[0084] (4) Add 95% ethanol solution to the first filter residue of Lithospermum officinale and soak for 2 hours; the mass volume ratio of the first filter residue of Lithospermum officinale to the 95% ethanol solution is 1:5.

[0085] (5) Heat in a water bath at 60°C for 3 h.

[0086] (6) Filter for the second time to obtain the second filtrate of Lithospermum officinale.

[0087] (7) combining the first filtrate of Lithospermum erythrorhizon and the second filtrate of Lithospermum erythrorhizon to obtain the total filtrate of Lithospermum erythrorhizon.

[0088] (8) Add 2% sodium hydroxide solution to the total filtrate of Lithospermum officinale to adjust the pH value to 11.0, and then use hydrochloric acid solution to adjust the pH value to 2.0 to obtain Lithospermum officinale concentrated solution.

[0089] (9) Drying under reduced pressure: The lithospermum erythrorhizon concentrate was concentrated under reduced pressure using a rotary evaporator in a water bath at 45°C to recover most of the ethanol to 1 / 10 of the original volume to obtain lithospermum erythrorhizon extract.

[0090] (10) The lithospermum extract was transferred to a culture dish and placed in a 50°C oven in the dark to dry for about 2 h until constant weight was obtained to obtain the lithospermum extract.

[0091] S2: Preparation of Litsea cubeba ethanol extract:

[0092] (1) The fresh fruits of Litsea cubeba were air-dried at room temperature for 10 days.

[0093] (2) Dry in an electric constant temperature blast drying oven.

[0094] (3) Grind and sieve to 40 mesh to obtain Litsea cubeba powder, which is sealed and stored for later use.

[0095] (4) Accurately weigh 10 g of Litsea cubeba powder, add 95% ethanol solution, and soak at 30°C for 2 h; the mass-to-volume ratio of Litsea cubeba powder to 95% ethanol solution is 1:10.

[0096] (5) The first filtration is performed to obtain the first filtrate of Litsea cubeba and the first filtrate residue of Litsea cubeba. The first filtrate of Litsea cubeba is stored separately for later use.

[0097] (6) Add 95% ethanol solution to the first filter residue of Litsea cubeba and soak at 30°C for 3 h. The mass volume ratio of the first filter residue of Litsea cubeba to the 95% ethanol solution is 1:10.

[0098] (7) Filter for the second time to obtain the second filtrate of Litsea cubeba.

[0099] (8) The first filtrate of Litsea cubeba and the second filtrate of Litsea cubeba are combined to obtain the total filtrate of Litsea cubeba.

[0100] (9) Drying under reduced pressure: The total filtrate of Litsea cubeba was concentrated under reduced pressure using a rotary evaporator in a water bath at 45°C to recover most of the ethanol to 1 / 10 of the original volume to obtain Litsea cubeba extract.

[0101] (10) The Litsea cubeba extract was transferred to a Petri dish and placed in a 50°C oven in the dark to dry for about 2 h until constant weight was obtained to obtain the Litsea cubeba alcohol extract.

[0102] S3: Sieving: Pass the lithospermum officinale extract, Litsea cubeba ethanol extract, PVP-k30, mannitol, sodium bicarbonate, citric acid, and PEG6000 through a 60-mesh sieve respectively.

[0103] S4: Dry the sieved raw materials in a drying oven at 105° C. for 4 h to constant weight.

[0104] S5: First mixing: fully and evenly mix the dried lithospermum erythrorhizon extract, the alcohol extract of Litsea cubeba, mannitol, PVP K30 and citric acid to obtain a first mixture.

[0105] S6: Second mixing: adding sodium bicarbonate to the first mixture and mixing thoroughly to obtain a second mixture.

[0106] S7: Third mixing: fully mix the second mixture and PEG6000 to obtain the third mixture.

[0107] S8: Tableting: The third mixture is compressed into tablets using a tablet press to obtain effervescent tablets, each weighing 0.585±0.04 g.

[0108] When the effervescent tablets are used, 500 mL of water is added to each effervescent tablet to obtain a solution for disinfection and antibacterial treatment.

[0109] Test Example 1

[0110] This test example is used to illustrate the antibacterial effect of the Lithospermum officinale effervescent tablets of Example 1.

[0111] (1) Preparation of drug-containing experimental samples: dissolve one effervescent tablet in 500 mL of water to obtain an aqueous solution; select a uniform, dry and sterile filter paper and punch it into round paper pieces (5 mm in diameter) with a hole punch; after high-pressure sterilization, add 10 μL of the above aqueous solution to each piece; use a clamping tool (sterile tweezers) to pick up the paper piece and place it in a 37°C drying oven to dry it to obtain the drug-containing filter paper piece for later use.

[0112] (2) Preparation of negative control sheets: Select filter paper sheets with uniform texture, dry and sterile, and punch them into round pieces (5 mm in diameter) with a hole punch. After high-pressure sterilization, add 5 μL of sterile distilled water to each piece, and use a clamping tool (sterile tweezers) to take the paper sheet and place it in a 37°C drying oven to dry it to obtain a drug-free filter paper sheet for later use.

[0113] (3) Preparation of culture medium: Trypticase soy peptone liquid culture medium (purchased from Guangdong Huankai Microbial Technology Co., Ltd.) was selected, which contained: 17 g trypticase, 3 g soybean papain hydrolyzate, 5 g sodium chloride, 2.5 g potassium dihydrogen phosphate, and 2.5 g glucose, with a final pH value of 7.3 ± 0.2; the volume was made up to 300 mL with deionized water, and the prepared culture medium was divided into 500 mL conical flasks for easy sterilization, sealed, and set aside.

[0114] (4) Sterilization and inoculation of culture medium: Place the sealed culture medium in a high-pressure steam sterilizer for sterilization; after sterilization, continue to complete the plate pouring operation on the clean bench, pour the liquid culture medium into the agar plate to form a flat culture medium surface to facilitate the growth and observation of colonies; the liquid culture medium is stored for future use.

[0115] After heating the inoculating loop in the outer flame of an alcohol lamp, use the inoculating loop to dip the purchased Escherichia coli (bacteria), Staphylococcus aureus (bacteria), Candida albicans (fungus), and Pseudomonas aeruginosa (bacteria) strains and streak them on the flat culture medium. Culture them at a constant temperature of 37°C for 24 hours to obtain colonies of the four bacteria. Under sterile conditions, use the burned inoculating loop to pick up the four colonies and transfer them to 10 mL of LB liquid culture medium. Culture them on a constant temperature shaker for 18 hours to obtain the test bacterial suspension. Store the bacterial suspension in a refrigerator for later use.

[0116] (5) Antibacterial test: Under sterile conditions, a sterile cotton swab was used to swab the sample with a specified concentration (1×10 8 A freshly prepared suspension of test bacteria (CFU) was evenly spread three times on the surface of an appropriate culture medium plate. The plate should be rotated 60° after each application. Finally, the cotton swab was spread around the edge of the plate. The plate was covered and dried at room temperature for 5 minutes.

[0117] Place a contaminated plate in each experiment, with 4 experimental samples and 1 negative control sample on each plate; the centers of the samples should be at least 25 mm apart, and the center of the sample should be at least 15 mm away from the edge of the plate; after placement, use sterile tweezers to gently press the sample to make it stick to the surface of the plate, cover the plate, place it in a constant temperature incubator, and incubate it at an appropriate temperature for 16-18 hours; take it out for observation, measure the diameter of the antibacterial ring with a vernier caliper and record it, and obtain the antibacterial effect of the shikonin effervescent tablets.

[0118] The above antibacterial experiment was repeated 3 times, and the results are shown in Table 1.

[0119] Table 1 Antibacterial experimental data

[0120]

[0121] From the data in Table 1, it can be found that the lithospermum officinale effervescent tablets provided in Example 1 of the present invention have obvious antibacterial effects on various pathogens after dissolution.

[0122] Example 2

[0123] This example is used to illustrate the ingredient ratio and preparation method of a shikonin preparation for antibacterial cleaning in the form of an effervescent tablet.

[0124] The raw materials of the Lithospermum officinale effervescent tablets of the present embodiment contain:

[0125] Lithospermum officinale extract 1g, Litsea cubeba alcohol extract 1g, PVP-k30 6g, mannitol 50g, sodium bicarbonate 30g, citric acid 25g, PEG6000 10g.

[0126] The preparation method of the above-mentioned Lithospermum officinale effervescent tablets is carried out with reference to Example 1, and the operations and parameters adopted are the same as those in Example 1.

[0127] According to the detection method of detection example 1, the antibacterial experiment was repeated 3 times, and the results are shown in Table 2.

[0128] Table 2 Antibacterial experimental data

[0129]

[0130]

[0131] From the data in Table 2, it can be found that the lithospermum officinale effervescent tablets provided in Example 2 of the present invention have obvious antibacterial effects on various pathogens after dissolution.

[0132] Example 3

[0133] This example is used to illustrate the ingredient ratio and preparation method of a shikonin preparation for antibacterial cleaning in the form of an effervescent tablet.

[0134] The raw materials of the Lithospermum officinale effervescent tablets of the present embodiment contain:

[0135] Lithospermum officinale extract 5g, Litsea cubeba alcohol extract 5g, PVP-k30 2g, mannitol 30g, sodium bicarbonate 20g, citric acid 15g, PEG6000 5g.

[0136] The preparation method of the above-mentioned Lithospermum officinale effervescent tablets is carried out with reference to Example 1, and the operations and parameters adopted are the same as those in Example 1.

[0137] According to the detection method of detection 1, the antibacterial experiment was repeated 3 times, and the results are shown in Table 3.

[0138] Table 3 Antibacterial experimental data

[0139]

[0140] From the data in Table 3, it can be found that the lithospermum officinale effervescent tablets provided in Example 3 of the present invention have obvious antibacterial effects on various pathogens after dissolution.

[0141] Example 4

[0142] This example is used to illustrate the ingredient ratio and preparation method of a shikonin preparation for antibacterial cleaning in the form of an effervescent tablet.

[0143] The raw materials of the Lithospermum officinale effervescent tablets of the present embodiment contain:

[0144] Lithospermum officinale extract 2g, Litsea cubeba alcohol extract 4g, PVP-k30 5g, mannitol 35g, sodium bicarbonate 28g, citric acid 22g, PEG6000 8g.

[0145] The preparation method of the above-mentioned Lithospermum officinale effervescent tablets is carried out with reference to Example 1, and the operations and parameters adopted are the same as those in Example 1.

[0146] According to the detection method of test 1, the antibacterial experiment was repeated 3 times, and the results are shown in Table 4.

[0147] Table 4 Antibacterial experimental data

[0148]

[0149] From the data in Table 4, it can be found that the lithospermum officinale effervescent tablets provided in Example 4 of the present invention have obvious antibacterial effects on various pathogens after dissolution.

[0150] Comparative Example 1

[0151] This comparative example is used to illustrate the antibacterial effect of Lithospermum officinale effervescent tablets without adding Litsea cubeba ethanol extract.

[0152] The raw materials of the Lithospermum officinale effervescent tablets of the present embodiment contain:

[0153] Lithospermum officinale extract 2.5g, PVP-k30 4g, mannitol 40g, sodium bicarbonate 25g, citric acid 20g, PEG6000 6g.

[0154] The preparation method of the above-mentioned Lithospermum officinale effervescent tablets is as described in Example 1. Except that the alcohol extract of Litsea cubeba is not added, the operation and parameters are the same as those in Example 1.

[0155] According to the test method of Test Example 1, the results are shown in Table 5.

[0156] Table 5 Antibacterial experimental data

[0157]

[0158] From the data in Table 5, it can be found that if the alcohol extract of Litsea cubeba is not added, the antibacterial effect of the effervescent tablets on various pathogens will be significantly reduced after dissolution.

[0159] Comparative Example 2

[0160] This comparative example is used to illustrate the antibacterial effect of an effervescent tablet without adding Lithospermum erythrorhizon extract.

[0161] The raw materials of the effervescent tablet of the present embodiment contain:

[0162] Litsea cubeba ethanol extract 2.5g, PVP-k30 4g, mannitol 40g, sodium bicarbonate 25g, citric acid 20g, PEG60006g.

[0163] The preparation method of the effervescent tablet is as described in Example 1. Except that the lithospermum erythrorhizon extract is not added, the operation and parameters are the same as those in Example 1.

[0164] According to the test method of Test Example 1, the results are shown in Table 6.

[0165] Table 6 Antibacterial experimental data

[0166]

[0167]

[0168] From the data in Table 6, it can be found that if the lithospermum erythrorhizon extract is not added, the antibacterial effect on various pathogens will be significantly reduced after the effervescent tablet is dissolved.

[0169] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A shikonin preparation, characterized in that: The preparation is made from the following raw materials in parts by weight: 1-5 parts by weight of Lithospermum officinale extract, 1-5 parts by weight of Litsea cubeba ethanol extract, and 10-150 parts by weight of auxiliary materials.

2. The shikonin preparation according to claim 1, wherein: The preparation is made from the following raw materials in parts by weight: 1-4 parts by weight of Lithospermum officinale extract, 1-4 parts by weight of Litsea cubeba ethanol extract, and 92-98 parts by weight of auxiliary materials.

3. The shikonin preparation according to claim 1, characterized in that: The preparation is made from the following raw materials in parts by weight: 2-3 parts by weight of Lithospermum officinale extract, 2-3 parts by weight of Litsea cubeba ethanol extract, and 94-96 parts by weight of auxiliary materials.

4. The shikonin preparation according to claim 1, characterized in that: The preparation is made from the following raw materials in parts by weight: 2.5 parts by weight of Lithospermum officinale extract, 2.5 parts by weight of Litsea cubeba ethanol extract, and 95 parts by weight of auxiliary materials.

5. The shikonin preparation according to any one of claims 1 to 4, characterized in that: The lithospermum officinale extract is extracted from the root of lithospermum officinale, and the litsea cubeba ethanol extract is extracted from the fruit of litsea cubeba.

6. The shikonin preparation according to claim 5, characterized in that: The preparation method of the lithospermum officinale extract comprises the following steps: Soak the roots of Lithospermum officinale in 95% ethanol solution for 1 to 3 hours, with the mass to volume ratio of the two being 1:(5 to 10); Heat in a water bath at 50-80°C for 2-4 hours; Filter again for the first time to obtain the first filter residue of Lithospermum officinale and the first filtrate of Lithospermum officinale; Adding 95% ethanol solution to the first filter residue of Lithospermum officinale at a mass volume ratio of 1: (5-10); Heat in a water bath at 50-80°C for 2-4 hours; Filter again for the second time to obtain the second filtrate of Lithospermum officinale; combining the first filtrate of Lithospermum erythrorhizon and the second filtrate of Lithospermum erythrorhizon to obtain a total filtrate of Lithospermum erythrorhizon; Then, sodium hydroxide solution is added to the total filtrate of lithospermum to adjust the pH value to 10.5-11.5, and then hydrochloric acid is used to adjust the pH value to 1.5-2.5 to obtain lithospermum concentrate; Concentrating the lithospermum erythrorhizon concentrate under reduced pressure to 1 / 10 to 1 / 5 of its original volume to obtain lithospermum erythrorhizon extract; The lithospermum erythrorhizon extract is then dried to a constant weight to obtain the lithospermum erythrorhizon extract.

7. The shikonin preparation according to claim 5 or 6, characterized in that: The preparation method of the Litsea cubeba ethanol extract comprises the following steps: Dry the fresh fruits of Litsea cubeba and then dry them in an oven; Then grind it into 30-50 mesh to obtain Litsea cubeba powder; Adding 95% ethanol solution to the Litsea cubeba powder in a mass-to-volume ratio of 1:(5-15); Soak at 20-40℃ for 1-3h; Filter again for the first time to obtain the first filtrate of Litsea cubeba and the first filtrate residue of Litsea cubeba; Adding 100% ethanol or 95% ethanol solution to the first filter residue of Litsea cubeba, with the mass volume ratio of the two being 1:(5-10); Soak at 20-40℃ for 1-3h; Filter again for the second time to obtain the second filtrate of Litsea cubeba; combining the first filtrate of Litsea cubeba and the second filtrate of Litsea cubeba to obtain a total filtrate of Litsea cubeba; The total filtrate of Litsea cubeba is then concentrated under reduced pressure to 1 / 10 to 1 / 5 of the original volume to obtain Litsea cubeba extract; The Litsea cubeba extract is dried to a constant weight to obtain Litsea cubeba ethanol extract.

8. The shikonin preparation according to claim 7, characterized in that: The dosage form of the shikonin preparation is tablets, granules, or powders, preferably effervescent tablets; Preferably, when the dosage form of the shikonin preparation is an effervescent tablet, the excipients include: 2-6 parts by weight of cosolvent, 30-50 parts by weight of filler, 20-30 parts by weight of alkali source, 15-25 parts by weight of acid source, 5-10 parts by weight of lubricant; Preferably: The cosolvent is one or more of an inorganic compound, an organic acid and its salts, an amide or amine compound, and a water-soluble polymer compound; preferably polyvinyl pyrrolidone, more preferably PVP-k30; The filler is one or more of mannitol, starch, powdered sugar, dextrin, lactose, and microcrystalline cellulose; preferably mannitol; The lubricant is one or more of hydroxypropyl methylcellulose, glyceryl distearate, and polyethylene glycol; preferably PEG6000. The acid source is one or more of citric acid, tartaric acid, fumaric acid, adipic acid, PEG polyethylene glycol, malic acid, water-soluble amino acids, dilute mineral acids, and acid salts; preferably citric acid. The alkali source is one or more of sodium bicarbonate, sodium carbonate, and potassium carbonate; preferably, sodium bicarbonate is used.

9. The method for preparing the shikonin preparation according to any one of claims 1 to 8, characterized in that: The method comprises the following steps: mixing the lithospermum officinale extract, the litsea cubeba ethanol extract and auxiliary materials to obtain the shikonin preparation.

10. The method for preparing the shikonin preparation according to claim 9, wherein: The method comprises the following steps: Sieving: The lithospermum officinale extract, litsea cubeba alcohol extract, cosolvent, filler, lubricant, acid source, and alkali source are sieved separately; the sieving process uses a 40-80 mesh sieve; Drying: drying the sieved lithospermum extract, litsea cubeba ethanol extract, cosolvent, filler, lubricant, acid source, and alkali source to constant weight; First mixing: mixing the dried lithospermum officinale extract, litsea cubeba ethanol extract, filler, cosolvent and acid source to obtain a first mixed material; Second mixing: mixing the alkali source and the first mixture to obtain a second mixture; Third mixing: mixing the lubricant and the second mixture to obtain a third mixture; Tableting: The third mixed material is tableted to obtain effervescent tablets.

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