Preparation method of pollen itching-relieving and pain-relieving preparation

Abstract

The invention discloses a preparation method of a pollen itching-relieving and pain-relieving preparation. The medicine formula of the pollen itching-relieving and pain-relieving preparation consists of a radix angelicae extract, a short-pedicel aconite root extract, a radix trichosanthis extract, a frankincense and myrrh mixed extract, frankincense and myrrh mixed volatile oil, borneol, camphor, peppermint oil and eucalyptus oil, methyl cellulose and dipolyglycerol dioleate are used as water-phase emulsifiers, and ascorbic acid is used as an antioxidant. The preparation is cream, is uniform and fine in texture, fine and smooth in appearance and good in flowability, is free of layering and foaming phenomena after centrifugation, and is free of layering and foaming phenomena after heat-resistant and cold-resistant stability tests.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical production, and particularly to a preparation method of a pollen antipruritic and analgesic preparation. Background Art

[0002] Pollen antipruritic and analgesic tincture is derived from the folk medicine of ethnic minorities. Snowdrop aconite has a strong analgesic effect and is used as the main drug. Angelica dahurica and Trichosanthes kirilowii Maxim. are used as adjuvant drugs, which have the effects of detumescence and antipruritic, and help snowdrop aconite play the effects of anti-inflammation and analgesia. Pain is caused by qi stagnation, and when qi flows smoothly, there is no pain. Therefore, frankincense and myrrh with the effects of promoting blood circulation to remove blood stasis and promoting qi circulation to relieve pain are used as adjuvant drugs. This formula has the effects of promoting blood circulation to remove blood stasis, detumescence and analgesia, and dispelling wind and relieving itching. This formula is used for promoting blood circulation to remove blood stasis, detumescence and analgesia, and dispelling wind and relieving itching, and the effect is obvious. In the prior art, pollen antipruritic and analgesic tincture is prepared as follows: Trichosanthes kirilowii Maxim., Angelica dahurica, snowdrop aconite, frankincense, and myrrh are crushed into coarse particles, mixed evenly, soaked with 80% ethanol for 24 hours, and then impregnated three times with 80% ethanol. The first time is for 3 hours; the second and third times are each for 2 hours. The three impregnation liquids are combined, filtered, and the filtrate is reserved; separately, borneol, camphor, peppermint oil, and eucalyptus oil are dissolved with 80% ethanol, added to the above filtrate, and then 80% ethanol is added to make 1000 ml, mixed evenly, allowed to stand for 24 hours, the supernatant is taken, and filtered to obtain the product. However, the inventor found in the research process that in the pollen antipruritic and analgesic tincture prepared by the existing extraction process, the active ingredients in medicinal materials such as Angelica dahurica and snowdrop aconite are not easily extracted. As a result, the clinical efficacy of pollen antipruritic and analgesic tincture is not yet ideal.

[0003] Therefore, while effectively extracting the active ingredients of medicinal materials such as Angelica dahurica and snowdrop aconite, the present invention prepares a pollen antipruritic and analgesic preparation with high bioavailability, long-lasting drug release, which can effectively treat mosquito bites and traumatic injuries, has high safety, and has a simple preparation process. Summary of the Invention

[0004] The purpose of the present invention is to provide a preparation method of a pollen antipruritic and analgesic preparation. The pharmaceutical preparation of the present invention has high bioavailability, can release the drug effect for a long time, can effectively treat mosquito bites and traumatic injuries, has high safety, and has a simple preparation process.

[0005] The technical solution of the present invention: A preparation method of a pollen antipruritic and analgesic preparation, the preparation method is carried out according to the following steps:

[0006] (1) Weigh 30 - 60 g of purified Angelica dahurica medicinal materials, crush them into coarse particles, add 4 - 8 times the amount of water, soak for 10 - 14 h, reflux and extract for 1.5 - 2.5 h, carry out vacuum filtration and collect the filtrate, and concentrate under reduced pressure to an extract with a relative density of 1.1 - 1.3 at 50 °C, namely obtain the Angelica dahurica extract, and reserve it for later use;

[0007] (2) Weigh 20 - 50 g of Aconitum brachypodum DC., crush it into coarse powder, add 8 - 12 times the amount of water, soak for 10 - 14 h, add 1 - 2 g of serine protease, heat in a water bath at 45 - 55 °C for 12 - 18 min, then decoct for 40 - 60 min. After filtration, adjust the pH value of the aqueous solution to 3 - 4 with 1% glacial acetic acid solution, let it stand for 8 - 12 h, filter, take the filtrate and separate it on a macroporous resin column, elute with 50 - 60% ethanol, collect the eluate, and concentrate it under reduced pressure to an extract with a relative density of 1.1 - 1.3 at 50 °C to obtain the Aconitum brachypodum DC. extract for standby;

[0008] (3) Weigh 30 - 60 g of Trichosanthes kirilowii Maxim., crush it into coarse granules, mix evenly, add 2 - 3 times the amount of 70 - 80% ethanol and soak for 1.5 - 2.5 h, then reflux extract with 70 - 80% ethanol at 35 - 45 °C for 2 times. The first time is for 2 - 4 h; the second time is for 0.5 - 1.5 h. Combine the two extraction solutions, filter to obtain the Trichosanthes kirilowii Maxim. extract for standby;

[0009] (4) Weigh 10 - 30 g of Olibanum and 10 - 30 g of Myrrha, crush them into fine powder, extract the volatile oil with steam to obtain the volatile oil and the drug residues respectively. The volatile oil is for standby; the drug residues are ultrasonically extracted 2 times with 1 - 3 times the amount of 95% ethanol. The first time is for 1.5 - 2.5 h, the second time is for 0.5 - 1.5 h. Combine the extraction solutions, filter to obtain the mixed extract of Olibanum and Myrrha, then add the Angelica dahurica extract, Aconitum brachypodum DC. extract and Trichosanthes kirilowii Maxim. extract, mix evenly to obtain Product A for standby;

[0010] (5) Weigh 3 - 8 g of Borneol, 3 - 8 g of Camphor, 10 - 30 g of Mentha oil and 3 - 8 g of Eucalyptus oil and grind them. After grinding evenly, add the volatile oil obtained in step (4) and mix evenly to obtain Product B;

[0011] (6) Take 200 mL of distilled water, heat it to 60 - 80 °C, add 5 - 15 g of methylcellulose and 10 - 20 g of diglycerol dioleate, stir for 50 - 70 min at a stirring speed of 800 - 1200 r / min; add 4 - 6 g of ascorbic acid, stir for 20 - 40 min at a stirring speed of 400 - 600 r / min. Add Product B at 40 - 50 °C while maintaining the temperature, stir at a stirring speed of 400 - 600 r / min, and let it cool overnight; at room temperature, add Product A and 0.8 - 1.2 g of Chlorobutanol, stir for 15 - 25 min at a stirring speed of 400 - 600 r / min, make up the volume to 500 mL with distilled water, stir evenly, stir for 15 - 25 min at a stirring speed of 400 - 600 r / min, sterilize, seal, and obtain the pollen antipruritic preparation.

[0012] In the aforementioned step (1), weigh 40 - 50 g of the purified Radix Angelicae Dahuricae, crush it into coarse particles, add 5 - 7 times the amount of water, soak for 11 - 13 h, reflux extract for 2 h, perform vacuum filtration and collect the filtrate, and concentrate it under reduced pressure to an extract with a relative density of 1.2 at 50 °C to obtain the Radix Angelicae Dahuricae extract for standby.

[0013] Specifically, in the aforementioned step (1), weigh 45 g of the purified Radix Angelicae Dahuricae, crush it into coarse particles, add 6 times the amount of water, soak for 12 h, reflux extract for 2 h, perform vacuum filtration and collect the filtrate, and concentrate it under reduced pressure to an extract with a relative density of 1.2 at 50 °C to obtain the Radix Angelicae Dahuricae extract for standby.

[0014] In the aforementioned step (2), weigh 30 - 40 g of Aconitum brachypodum Diels, crush it into coarse powder, add 9 - 11 times the amount of water, soak for 11 - 13 h, add 1.2 - 1.8 g of serine protease, heat in a water bath at 50 °C for 14 - 16 min, then decoct for 45 - 55 min. After filtration, adjust the pH value of the aqueous solution to 3 - 4 with 1% glacial acetic acid solution, soak for 9 - 11 h, remove the soaking solution, rinse with water until colorless, drain, then add 5 times the amount of 1 mol / L sodium hydroxide solution and soak for 4 - 6 h, then rinse with water until neutral, drain, and then add 5 times the amount of 55% ethanol and reflux extract 2 times, 2 h each time. Filter, combine the two extraction solutions, separate the extraction solution on a macroporous resin column, elute with 55% ethanol, collect the eluate, and concentrate it under reduced pressure to an extract with a relative density of 1.2 at 50 °C to obtain the Aconitum brachypodum Diels extract for standby.

[0015] Specifically, in the aforementioned step (2), weigh 35 g of Aconitum brachypodum Diels, crush it into coarse powder, add 10 times the amount of water, soak for 12 h, add 1.5 g of serine protease, heat in a water bath at 50 °C for 15 min, then decoct for 50 min. After filtration, adjust the pH value of the aqueous solution to 3 - 4 with 1% glacial acetic acid solution, soak for 10 h, remove the soaking solution, rinse with water until colorless, drain, then add 5 times the amount of 1 mol / L sodium hydroxide solution and soak for 5 h, then rinse with water until neutral, drain, and then add 5 times the amount of 55% ethanol and reflux extract 2 times, 2 h each time. Filter, combine the two extraction solutions, separate the extraction solution on a macroporous resin column, elute with 55% ethanol, collect the eluate, and concentrate it under reduced pressure to an extract with a relative density of 1.2 at 50 °C to obtain the Aconitum brachypodum Diels extract for standby.

[0016] In the aforementioned step (3), weigh 45 g of Trichosanthis Radix, crush it into coarse particles, mix evenly, add 2 times the amount of 75% ethanol and soak for 2 h, then reflux extract with 75% ethanol at 40 °C 2 times, the first time for 3 h; the second time for 1 h. Combine the two extraction solutions, filter to obtain the Trichosanthis Radix extract for standby.

[0017] In the aforesaid step (4), weigh 20 g of frankincense and 20 g of myrrh, pulverize them into fine powder, extract the volatile oil with steam, and obtain the volatile oil and the medicinal residues respectively. Reserve the volatile oil; extract the medicinal residues twice with 2 times the amount of 95% ethanol by ultrasonic wave, 2 h for the first time and 1 h for the second time. Combine the extraction solutions and filter to obtain the mixed extract of frankincense and myrrh. Then add the angelica dahurica extract, aconitum brachypodum extract and trichosanthes root extract, and mix evenly to obtain Product A for standby.

[0018] In the aforesaid step (5), weigh 5 g of borneol, 5 g of camphor, 20 g of peppermint oil and 5 g of eucalyptus oil and grind them. After grinding evenly, add the volatile oil obtained in step (4) and mix evenly to obtain Product B.

[0019] In the aforesaid step (6), take 200 mL of distilled water, heat it to 65 - 75 °C, add 8 - 12 g of methylcellulose and 12 - 18 g of diglycerol dioleate, stir for 55 - 65 min at a stirring speed of 1000 r / min; add 4.5 - 5.5 g of ascorbic acid, stir for 25 - 35 min at a stirring speed of 500 r / min, add Product B under the condition of keeping warm at 42 - 48 °C at a stirring speed of 500 r / min, and let it cool overnight; at room temperature, add Product A and 0.9 - 1.1 g of chlorobutanol, stir for 18 - 22 min at a stirring speed of 500 r / min, make up the volume to 500 mL with distilled water, stir evenly, stir for 18 - 22 min at a stirring speed of 500 r / min, sterilize, and seal to obtain the pollen antipruritic and analgesic tincture.

[0020] Specifically, in the aforesaid step (6), take 200 mL of distilled water, heat it to 70 °C, add 10 g of methylcellulose and 15 g of diglycerol dioleate, stir for 60 min at a stirring speed of 1000 r / min; add 5 g of ascorbic acid, stir for 30 min at a stirring speed of 500 r / min, add Product B under the condition of keeping warm at 45 °C at a stirring speed of 500 r / min, and let it cool overnight; at room temperature, add Product A and 1 g of chlorobutanol, stir for 20 min at a stirring speed of 500 r / min, make up the volume to 500 mL with distilled water, stir evenly, stir for 20 min at a stirring speed of 500 r / min, sterilize, and seal to obtain the pollen antipruritic and analgesic preparation.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] 1. By using the water extraction method for the angelica dahurica medicinal material, the effective components of the angelica dahurica can be effectively extracted, and the content of imperatorin in the angelica dahurica extract can reach 0.024%.

[0023] 2. Aconitum brachypodum contains a large amount of alkaloids, which are composed of mesaconitine, hypaconitine, aconitine, etc., and have the effects of expelling wind, anti - inflammation and analgesia. However, aconitine in the alkaloids has strong toxicity, and after long - term use, it causes great damage to the skin. In order to minimize the content of aconitine as much as possible, aiming at the characteristic that aconitine is a diester - type alkaloid and ensuring the effective extraction of other alkaloids, the present invention adopts the method of water extraction and enzymatic hydrolysis. The diester - type alkaloids in Aconitum brachypodum will undergo hydrolysis reaction, converting into monoester - type alkaloids with less toxicity, and further hydrolysis can turn them into almost non - toxic alcoholamine alkaloids, while ensuring the effective retention of the composition of alkaloids composed of mesaconitine, hypaconitine, aconitine, etc. Then, through the further separation and purification of macroporous resin, an Aconitum brachypodum extract with a higher content is obtained, and the content of mesaconitine reaches 0.154%.

[0024] 3. Frankincense and myrrh contain a large amount of volatile oils, which can promote blood circulation and play a role in dissipating blood stasis. However, a large amount of volatile oils are lost in the extraction method of traditional technology. Therefore, for the optimization of the extraction process of frankincense and myrrh, first, steam is used to extract the volatile oils, and then ethanol ultrasonic extraction is used. This not only effectively extracts the volatile oil components in the medicine, improves the curative effect of the medicine in dissipating blood stasis, but also ensures the effective extraction of other components in frankincense and myrrh.

[0025] 4. The cream prepared by the present invention has a uniform and delicate texture, a fine appearance, good fluidity, no stratification and foaming phenomenon after centrifugation, and no stratification and foaming phenomenon after heat - resistant and cold - resistant stability tests. Detailed implementation mode

[0026] The present invention will be further described in detail below in conjunction with the embodiments, but the implementation mode of the present invention is not limited thereto. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field. The test methods of the following embodiments without specific experimental conditions are usually carried out according to the conventional experimental conditions. Unless otherwise specified, the reagents used in the present invention can be obtained through commercial channels.

[0027] Example 1

[0028] (1) Weigh 45 g of the purified Angelica dahurica medicinal material, crush it into coarse particles, add 6 times the amount of water, soak for 12 h, reflux and extract for 2 h, carry out vacuum filtration and collect the filtrate. The filtrate is concentrated under reduced pressure to an extract with a relative density of 1.2 at 50 °C, that is, the Angelica dahurica extract is obtained and reserved for later use;

[0029] (2) Weigh 35 g of Aconitum brachypodum DC., crush it into coarse granules, add 10 times the amount of water, soak for 12 h, add 1.5 g of serine protease, heat in a water bath at 80 °C for 15 min, then decoct for 50 min. After filtration, adjust the pH value of the aqueous solution to 3 - 4 with 1% glacial acetic acid solution, let it stand for 10 h, filter, take the filtrate and separate it on a macroporous resin column, elute with 100 mL of 80% ethanol, collect the eluate, and concentrate it under reduced pressure to an extract with a relative density of 1.2 at 50 °C to obtain the Aconitum brachypodum DC. extract for standby;

[0030] (3) Weigh 45 g of Trichosanthes kirilowii Maxim., crush it into coarse granules, mix well, add 2 times the amount of 75% ethanol and soak for 2 h, then reflux extract with 75% ethanol at 40 °C for 2 times, 3 h for the first time and 1 h for the second time. Combine the two extraction solutions, filter to obtain the Trichosanthes kirilowii Maxim. extract for standby;

[0031] (4) Weigh 20 g of Olibanum and 20 g of Myrrha, crush them into fine powder, extract the volatile oil by steam distillation to obtain the volatile oil and the medicinal residues respectively. The volatile oil is for standby; the medicinal residues are ultrasonically extracted with 2 times the amount of 95% ethanol for 2 times, 60 min each time. Combine the extraction solutions, filter to obtain the mixed extract of Olibanum and Myrrha for standby;

[0032] (5) Add the mixed extract of Olibanum and Myrrha to the Angelica dahurica extract, Aconitum brachypodum DC. extract and Trichosanthes kirilowii Maxim. extract, mix well to obtain Product A for standby;

[0033] (6) Weigh 5 g of Borneol, 5 g of Camphor, 20 g of Mentha oil and 5 g of Eucalyptus oil, grind them evenly, then add the volatile oil obtained in step (4), mix well to obtain Product B;

[0034] (7) Take 100 mL of distilled water, heat it to 70 °C, add 10 g of methylcellulose and 15 g of diglycerol dioleate, stir for 60 min at a stirring speed of 1000 r / min; add 5 g of ascorbic acid, stir for 30 min at a stirring speed of 500 r / min, add Product B at a temperature of 45 °C under insulation state and stir at a speed of 500 r / min, let it cool overnight; at room temperature, add Product A and 1 g of chlorobutanol, stir for 20 min at a stirring speed of 500 r / min, make up the volume to 250 mL with distilled water, sterilize, seal to obtain the pollen antipruritic and analgesic cream.

[0035] Dosage and administration: Apply it to the affected area once in the morning and once in the evening every day.

[0036] Example 2

[0037] (1) Weigh 30 g of the pure Angelica dahurica medicinal material, crush it into coarse granules, add 8 times the amount of water, soak for 10 h, reflux extract for 2.5 h, carry out vacuum filtration and collect the filtrate. Concentrate the filtrate under reduced pressure to an extract with a relative density of 1.1 at 50 °C to obtain the Angelica dahurica extract for standby;

[0038] (2) Weigh 50 g of Aconitum brachypodum DC. and crush it into coarse granules. Add 12 times the amount of water, soak for 10 h, add 1 g of serine protease, heat in a water bath at 85 °C for 18 min, then decoct for 40 min. After filtration, adjust the pH value of the aqueous solution to 3 - 4 with 1% glacial acetic acid solution, let it stand for 8 h, filter, and separate the filtrate on a macroporous resin column. Elute with 80 mL of 90% ethanol, collect the eluate, and concentrate it under reduced pressure to obtain an extract with a relative density of 1.3 at 50 °C, which is the extract of Aconitum brachypodum DC. and reserve it for use;

[0039] (3) Weigh 60 g of Trichosanthes kirilowii Maxim. and crush it into coarse granules, mix them evenly, add 2 times the amount of 70% ethanol and soak for 2.5 h, then reflux and extract with 70% ethanol at 35 °C for 2 times. The first extraction is for 2 h; the second extraction is for 1.5 h. Combine the two extraction solutions, filter, and obtain the extract of Trichosanthes kirilowii Maxim. and reserve it for use;

[0040] (4) Weigh 30 g of Frankincense and 10 g of Myrrh, crush them into fine powder, extract the volatile oil by steam distillation to obtain the volatile oil and the medicinal residues respectively. Reserve the volatile oil for use; Ultrasonically extract the medicinal residues with 3 times the amount of 95% ethanol for 2 times, each time for 50 min. Combine the extraction solutions, filter, and obtain the mixed extract of Frankincense and Myrrh and reserve it for use;

[0041] (5) Add the mixed extract of Frankincense and Myrrh to the extract of Angelica dahurica (Fisch.) Benth. et Hook. f. ex Franch. et Sav., the extract of Aconitum brachypodum DC., and the extract of Trichosanthes kirilowii Maxim., mix them evenly to obtain Product A and reserve it for use;

[0042] (6) Weigh 3 g of Borneol, 8 g of Camphor, 30 g of Mentha oil, and 3 g of Eucalyptus oil and grind them. After grinding evenly, add the volatile oil obtained in step (4) and mix them evenly to obtain Product B;

[0043] (7) Take 70 mL of distilled water, heat it to 60 °C, add 15 g of methylcellulose and 10 g of diglycerol dioleate, stir for 50 min at a stirring speed of 800 r / min; add 6 g of ascorbic acid, stir for 20 min at a stirring speed of 400 r / min, add Product B under the condition of keeping warm at 450 °C, stir at a stirring speed of 400 r / min, and let it cool overnight; at room temperature, add Product A and 1 g of Chlorobutanol, stir for 25 min at a stirring speed of 400 r / min, make up the volume to 200 mL with distilled water, sterilize, seal, and obtain the Pollen Itch - relieving and Pain - relieving Cream.

[0044] Dosage and administration: Apply it to the affected area once in the morning and once in the evening every day.

[0045] Example 3

[0046] (1) Weigh 60 g of Angelica dahurica extract, grind it into coarse particles, add 4 times the amount of water, soak for 14 h, reflux for 1.5 h, filter under reduced pressure and collect the filtrate, and concentrate the filtrate under reduced pressure to an extract with a relative density of 1.3 at 50° C. to obtain the Angelica dahurica extract, which is set aside;

[0047] (2) Weigh 20 g of Artemisia sibiricum, crush it into coarse particles, add 8 times the amount of water, soak for 14 hours, add 2 g of serine protease, heat in a water bath at 75-85° C. for 12 minutes, and then boil for 60 minutes. After filtering, add 1% glacial acetic acid solution to adjust the pH value to 3-4, let stand for 12 hours, filter, take the filtrate and separate it on a macroporous resin column, use 120 mL of 70% ethanol to elute, collect the eluate, and concentrate it under reduced pressure to an extract with a relative density of 1.1 at 50° C., thereby obtaining an Artemisia sibiricum extract for later use;

[0048] (3) Weigh 30 g of Radix Trichosanthis, crush it into coarse particles, mix well, add 3 times the amount of 80% ethanol and soak for 1.5 hours, then use 80% ethanol to reflux and extract twice at 45°C, the first time for 4 hours and the second time for 0.5 hours, combine the two extracts, filter, and obtain the Radix Trichosanthis extract for later use;

[0049] (4) Weigh 10 g of frankincense and 30 g of myrrh, crush them into fine powder, extract volatile oil with water vapor, and obtain volatile oil and medicinal residue respectively, and set aside the volatile oil; extract the medicinal residue with 1 times the amount of 95% ethanol by ultrasonic twice, each time for 70 min, combine the extracts, filter, and obtain a mixed extract of frankincense and myrrh, which is set aside;

[0050] (5) Add the mixed extract of frankincense and myrrh to the angelica extract, the Artemisia annua extract and the Radix Trichosanthis extract, mix well, and obtain product A for later use;

[0051] (6) Weigh 8 g of borneol, 3 g of camphor, 10 g of peppermint oil and 8 g of eucalyptus oil, grind them evenly, add the volatile oil obtained in step (4), mix evenly, and obtain product B;

[0052] (7) Take 130 mL of distilled water, heat it to 80°C, add 5 g of methyl cellulose and 20 g of diglycerol dioleate, stir for 70 min at a stirring speed of 1200 r / min; add 4 g of ascorbic acid, stir for 40 min at a stirring speed of 600 r / min, add product B at a temperature of 40°C, stir at a speed of 600 r / min, and cool overnight; at room temperature, add product A and 1 g of trichlorobutanol, stir for 15 min at a stirring speed of 600 r / min, add distilled water to make up to 300 mL, sterilize, and fill to obtain a pollen anti-itch and analgesic cream.

[0053] Dosage and Administration: Apply to the affected area once a day, morning and evening.

[0054] Example 4

[0055] (1) Weigh 40 g of the purified Radix Angelicae Dahuricae medicinal material, crush it into coarse granules, add 6 times the amount of water, soak for 13 h, reflux extract for 1.8 h, carry out vacuum filtration and collect the filtrate. The filtrate is concentrated under reduced pressure to an extract with a relative density of 1.25 at 50 °C, namely, the Radix Angelicae Dahuricae extract, and set aside for later use.

[0056] (2) Weigh 40 g of Aconitum brachypodum Diels, crush it into coarse granules, add 10 times the amount of water, soak for 14 h, add 1.5 g of serine protease, heat in a water bath at 85 °C for 14 min, then carry out decoction for 55 min. After filtration, adjust the pH value of the aqueous solution to 3 - 4 with 1% glacial acetic acid solution, let it stand for 9 h, filter, take the filtrate and separate it on a macroporous resin column, elute with 110 mL of 80% ethanol, collect the eluate, and concentrate it under reduced pressure to an extract with a relative density of 1.15 at 50 °C, namely, the Aconitum brachypodum Diels extract, and set aside for later use.

[0057] (3) Weigh 40 g of Trichosanthis Radix, crush it into coarse granules, mix evenly, add 3 times the amount of 80% ethanol and soak for 2.5 h, then reflux extract twice with 75% ethanol at 40 °C, the first time for 3 h; the second time for 1.5 h. Combine the two extraction solutions, filter, and obtain the Trichosanthis Radix extract, and set aside for later use.

[0058] (4) Weigh 20 g of Olibanum and 20 g of Myrrha, crush them into fine powders, extract the volatile oil by steam distillation to obtain the volatile oil and the drug residues respectively. The volatile oil is set aside for later use; the drug residues are ultrasonically extracted twice with 2 times the amount of 95% ethanol, each time for 65 min. Combine the extraction solutions, filter, and obtain the mixed extract of Olibanum and Myrrha, and set aside for later use.

[0059] (5) Add the mixed extract of Olibanum and Myrrha to the Radix Angelicae Dahuricae extract, Aconitum brachypodum Diels extract, and Trichosanthis Radix extract, mix evenly, namely, obtain Product A, and set aside for later use.

[0060] (6) Weigh 6 g of Borneolum Syntheticum, 5 g of Camphora, 20 g of Mentha Oil, and 5 g of Eucalyptus Oil, grind them, and after grinding evenly, add the volatile oil obtained in step (4), mix evenly to obtain Product B.

[0061] (7) Take 110 mL of distilled water, heat it to 75 °C, add 10 g of Methylcellulose and 12 g of diglycerol dioleate, stir for 60 min, and the stirring speed is 1000 r / min; add 1.5 g of Ascorbic Acid, stir for 30 min, and the stirring speed is 450 r / min. Add Product B under the condition of maintaining at 40 °C, and the stirring speed is 450 r / min. Let it cool overnight; at room temperature, add Product A and 1 g of Chlorobutanol, stir for 18 min, and the stirring speed is 450 r / min. Make up the volume to 250 mL with distilled water, sterilize, seal, and namely obtain the pollen antipruritic and analgesic cream.

[0062] Dosage and administration: Apply once in the morning and once in the evening every day, apply it to the affected area.

[0063] To verify the beneficial effects of the present invention, the inventor conducted a large number of experimental studies. The experimental process and results are as follows:

[0064] 1 Investigation of single factors in the extraction process

[0065] 1.1 Investigation of the extraction process of Angelica dahurica

[0066] Weigh 45 g of the purified Angelica dahurica medicinal materials, crush them into coarse particles, and respectively investigate the addition of 6 times the amount of water, 75% ethanol, and 95% ethanol. After soaking for 12 h, reflux extract (for 1 h and 2 h), then perform vacuum filtration and collect the filtrate. The filtrate is concentrated under reduced pressure to an extract with a relative density of 1.2 at 50 °C, that is, the Angelica dahurica extract is obtained. Determine the content of imperatorin in the Angelica dahurica extract by the high performance liquid chromatography method (General Principles 0512), and at the same time calculate the extract yield. The results are shown in Table 1.

[0067] Table 1 Experimental grouping and results of the Angelica dahurica extraction method

[0068] Extraction solvent Extraction time Imperatorin content Water 1h 0.021％ Water 2h 0.024％ 75% ethanol 1h 0.017％ 75% ethanol 2h 0.019％ 95% ethanol 1h 0.012％ 95% ethanol 2h 0.014％

[0069] Therefore, it is determined that the best extraction process for Angelica dahurica uses water as the solvent, performs reflux extraction, and the extraction time is 2 h.

[0070] 1.2 Investigation of the extraction process of Aconitum brachypodum

[0071] Aconitum brachypodum is a Chinese medicinal material in the prescription of Huafen Quyang Zhitong Tincture. The main active ingredients of Aconitum brachypodum are alkaloids, which are composed of mesaconitine, hypaconitine, and aconitine, etc., and have the effects of dispelling wind, anti - inflammation, and analgesia. However, aconitine in the alkaloids contains strong toxicity, and after long - term use, it causes greater damage to the skin. In order to minimize the content of aconitine as much as possible and ensure the effective extraction of other alkaloids, the applicant conducted experiments on the extraction process of Aconitum brachypodum and made a comparative analysis with the original process. The experimental methods and data are as follows:

[0072] Extraction by water extraction and enzymatic hydrolysis method: Weigh 35 g of Aconitum brachypodum, crush it into coarse particles, add (8 times the amount, 10 times the amount, 12 times the amount) of water, soak for 12 h, add serine protease (0.5 g, 1.5 g, 3 g), heat in a water bath at 80 °C for 15 min, then perform decoction (40 min, 50 min, 60 min). After filtration, add 1% glacial acetic acid solution to the aqueous solution to adjust the pH value to 3 - 4, let it stand for 10 h, filter, take the filtrate and separate it on a separation column (macroporous resin, polyamide resin, and ion exchange resin), elute with 100 mL of 80% ethanol, collect the eluate, and concentrate it under reduced pressure to an extract with a relative density of 1.2 at 50 °C, that is, the Aconitum brachypodum extract is obtained.

[0073] Traditional method extraction: Take 35 g of Aconitum brachypodum, crush it into coarse particles, mix well, moisten it with 2 times the amount of 80% ethanol for 24 hours, then impregnate it three times with 80% ethanol, the first time for 3 hours; the second and third times for 2 hours each. Combine the three impregnation solutions, filter, collect the filtrate, and concentrate it under reduced pressure to an extract with a relative density of 1.2 at 50 °C to obtain the Aconitum brachypodum extract.

[0074] Examine the use of different amounts of serine protease, water addition, decoction time, and different resin columns to extract the aconitine content of Aconitum brachypodum, and compare it with the traditional method. According to the spectrophotometry method (Appendix 0401, Volume IV of the Chinese Pharmacopoeia 2020 Edition), measure the absorbance of the Aconitum brachypodum extract at a wavelength of 416 nm, and measure the content of mesaconitine (aconitine). At the same time, use thin-layer chromatography for the limit detection of aconitine to confirm whether the spots that appear at the corresponding positions of the chromatogram of the reference substance are smaller than those of the reference substance or do not show spots. The results are shown in Table 2.

[0075] Table 2 Experimental grouping and results of the extraction method of Aconitum brachypodum

[0076]

[0077] It can be seen from Table 2 that the optimal scheme in the water extraction and enzymatic hydrolysis method is to use 10 times the amount of water, the serine protease dosage is 1.5 g, the decoction time is 50 min, and after purification with macroporous resin, the content of mesaconitine detected in the Aconitum brachypodum extract reaches the highest 0.154%, and no aconitine is detected. At the same time, the optimal scheme in the enzyme extraction method is also better than the traditional method. Not only is the content of mesaconitine in the extract higher than that of the traditional method, but the removal effect of aconitine is also better than that of the traditional method.

[0078] 1.3 Optimization of the extraction process of frankincense and myrrh

[0079] Experimental method:

[0080] 1) Weigh 20 g of frankincense and 20 g of myrrh, crush them into fine powder, extract the volatile oil with steam, and obtain the volatile oil and the medicinal residues respectively. The volatile oil is reserved for later use;

[0081] 2) Ultrasonically extract the medicinal residues with ethanol twice, combine the extraction solutions, and filter to obtain the mixed extract of frankincense and myrrh.

[0082] Take the mixed extract of frankincense and myrrh and dry it at 70 °C to obtain a dry extract. Use the dry extract yield to examine three variables: ethanol concentration, ethanol dosage, and ultrasonic extraction time. The three variables are designed according to the following schemes respectively: the ethanol concentrations are 75% ethanol, 85% ethanol, and 95% ethanol, the ethanol dosage is 1 time, 2 times, and 3 times the dosage of the medicinal materials, and the ultrasonic extraction time is 40 min, 50 min, and 60 min each time. The yield of the mixed extract is calculated according to the following formula:

[0083] The yield of dry extract = (mass of dry extract ÷ total mass of traditional Chinese medicine) × 100%;

[0084] The total mass of traditional Chinese medicine is the sum of the masses of frankincense and myrrh.

[0085] Table 3 Experimental combinations and results

[0086]

[0087] As can be seen from Table 3, the ethanol concentration, ethanol dosage, and ultrasonic extraction time all have an impact on the extraction rate of the medicinal materials. The extract yield of the 5th group in the experiment is the highest. The yield of the dry extract with 95% ethanol, 2 times the ethanol dosage, and 60 min of ultrasonic time each time is the largest, reaching 21.73%.

[0088] 1.4 Discussion

[0089] 1) According to the verification of the extraction process, the optimal parameters for the extraction process of Angelica dahurica are as follows: using water as the solvent, carrying out reflux extraction, and the extraction time is 2 h.

[0090] 2) According to the verification of the extraction process, the optimal parameters for the extraction process of Aconitum brachypodum are as follows: the water consumption is 10 times the amount of the medicinal material, the dosage of serine protease is 1.5 g, the decocting time is 50 min, and macroporous resin is used for purification.

[0091] 3) According to the verification of the extraction process, the optimal parameters for the extraction process of the residues of frankincense and myrrh are as follows: using 95% ethanol as the extraction solvent, 2 times the ethanol dosage, and 60 min of ultrasonic time each time.

[0092] 2 Optimization of the preparation process

[0093] 2.1 Design of the preparation process plan: Take 100 mL of distilled water, heat it to 70 °C, add an emulsifier and stir for 60 min, with a stirring speed of 1000 r / min; add 5 g of ascorbic acid and stir for 30 min, with a stirring speed of 500 r / min. Add Product B under the condition of maintaining a temperature of 45 °C and stir at a speed of 500 r / min. Let it cool overnight; at room temperature, add Product A and stir for 20 min, with a stirring speed of 500 r / min. Make up the volume to 250 mL with distilled water, sterilize, and seal to obtain the pollen antipruritic and analgesic tincture cream.

[0094] Methyl cellulose 10 g, polyvinyl alcohol 10 g, and diglycerol dioleate 15 g are selected for investigation as emulsifiers, and their fineness, fluidity, stability and other indicators are investigated, so as to optimize the best emulsifier to prepare the pollen antipruritic and analgesic cream. Table 4 shows the experimental grouping of different emulsifiers.

[0095] Table 4 Experimental grouping of different emulsifiers

[0096] Experimental grouping Methyl cellulose Polyvinyl alcohol Dimeric glycerol dioleate 1 10g 5g / 2 5g 15g / 3 15g 10g / 4 / 10g 20g 5 / 15g 10g 6 / 5g 15g 7 5g / 10g 8 10g / 15g 9 15g / 20g

[0097] 2.2 Stability test

[0098] 2.2.1 Centrifugal stability test

[0099] Place the pollen antipruritic and analgesic cream in a centrifuge and centrifuge at 3000 r / min for 15 min, and observe whether there is oil-water separation.

[0100] 2.2.2 Heat and cold resistance stability test

[0101] Heat resistance test: Place the pollen antipruritic and analgesic cream in a constant temperature environment of 55 °C for 6 hours, and observe whether there is oil-water separation. If oil-water separation occurs, it indicates that the ointment has poor stability at high temperatures.

[0102] Cold resistance test: Place the ointment in an environment of -15 °C for 24 hours, and then observe whether there is oil-water separation or the texture becomes coarser. Tables 4 and 5 are the quality evaluation standard table and quality evaluation results of the cream of the present invention respectively.

[0103] Table 4 Quality evaluation standard table of cream

[0104]

[0105] Table 5 Quality evaluation results of different emulsifier experimental groups

[0106]

[0107] It can be seen that when the emulsifiers are selected as 10 g of methylcellulose and 15 g of diglycerol dioleate, the quality evaluation score is the highest, the appearance is delicate, the fluidity is good, there is no layering or foaming after centrifugation, and there is no layering or foaming after heat and cold resistance stability tests.

[0108] 2.3 Discussion:

[0109] In this experiment, the indexes such as fineness, fluidity and stability were used as the investigation indexes to screen the dosage of excipients in the cream preparation process. It was found that when methylcellulose and diglycerol dioleate were used as emulsifiers, the prepared cream had a uniform and delicate texture, a delicate appearance, good fluidity, no layering or foaming after centrifugation, and no layering or foaming after heat and cold resistance stability tests. If the dosage of methylcellulose is too small, the fineness will decrease, and if the dosage is too large, the fluidity will be affected.

Claims

1. A method for preparing a pollen antipruritic and analgesic preparation, characterized in that: The preparation method is carried out according to the following steps: (1) Weigh 30-60 g of Angelica dahurica extract, grind into coarse particles, add 4-8 times the amount of water, soak for 10-14 hours, reflux for extraction for 1.5-2.5 hours, filter under reduced pressure and collect the filtrate, and concentrate the filtrate under reduced pressure to an extract with a relative density of 1.1-1.3 at 50° C. to obtain the Angelica dahurica extract, which is set aside; (2) Weigh 20-50 g of Artemisia sibiricum, crush into coarse particles, add 8-12 times the amount of water, soak for 10-14 hours, add 1-2 g of serine protease, heat in a water bath at 75-85° C. for 12-18 minutes, and then boil for 40-60 minutes. After filtering, add 1% glacial acetic acid solution to adjust the pH value to 3-4, let stand for 8-12 hours, filter, take the filtrate and separate it on a macroporous resin column, use 70-90% ethanol 80-120 mL to elute, collect the eluate, and concentrate under reduced pressure to an extract with a relative density of 1.1-1.3 at 50° C., thereby obtaining an Artemisia sibiricum extract for later use; (3) Weigh 30-60 g of Radix Trichosanthis, crush it into coarse particles, mix well, add 2-3 times the amount of 70-80% ethanol and soak for 1.5-2.5 hours, then use 70-80% ethanol to reflux and extract twice at 35-45° C., the first time for 2-4 hours and the second time for 0.5-1.5 hours, combine the two extracts, filter, and obtain the Radix Trichosanthis extract for later use; (4) Weigh 10-30 g of frankincense and 10-30 g of myrrh, crush them into fine powder, extract volatile oil with water vapor, and obtain volatile oil and medicinal residue respectively, and set aside the volatile oil; extract the medicinal residue with 1-3 times the amount of 95% ethanol by ultrasonic twice, each time for 50-70 min, combine the extracts, filter, and obtain a mixed extract of frankincense and myrrh, which is set aside; (5) Add the mixed extract of frankincense and myrrh to the angelica extract, the Artemisia annua extract and the Radix Trichosanthis extract, mix well, and obtain product A for later use; (6) Weigh 3-8 g of borneol, 3-8 g of camphor, 10-30 g of peppermint oil and 3-8 g of eucalyptus oil, grind them evenly, add the volatile oil obtained in step (4), mix evenly, and obtain product B; (7) Take 70-130 mL of distilled water, heat it to 60-80° C., add 5-15 g of methyl cellulose and 10-20 g of diglycerol dioleate, stir for 50-70 min at a stirring speed of 800-1200 r / min; add 4-6 g of ascorbic acid, stir for 20-40 min at a stirring speed of 400-600 r / min, add product B at a temperature of 40-50° C., stir at a speed of 400-600 r / min, and cool overnight; at room temperature, add product A and 1 g of trichlorobutanol, stir for 15-25 min at a stirring speed of 400-600 r / min, add distilled water to make up to 200-300 mL, sterilize, and fill to obtain a pollen antipruritic and analgesic preparation.

2. The method for preparing the pollen antipruritic and analgesic preparation according to claim 1, characterized in that: In the step (1), 40-50 g of Angelica dahurica extract is weighed, crushed into coarse particles, added with 5-7 times the amount of water, soaked for 11-13 hours, refluxed for extraction for 2 hours, filtered under reduced pressure and the filtrate is collected, and the filtrate is concentrated under reduced pressure to an extract with a relative density of 1.15-1.25 at 50° C., thereby obtaining the Angelica dahurica extract for later use.

3. The method for preparing the pollen antipruritic and analgesic preparation according to claim 2, characterized in that: In the step (1), 45 g of Angelica dahurica extract is weighed, crushed into coarse particles, added with 6 times the amount of water, soaked for 12 hours, refluxed for extraction for 2 hours, filtered under reduced pressure and the filtrate is collected, and the filtrate is concentrated under reduced pressure to an extract with a relative density of 1.2 at 50° C., thereby obtaining the Angelica dahurica extract for later use.

4. The method for preparing the pollen antipruritic and analgesic preparation according to claim 1, characterized in that: In the step (2), 30-40 g of Artemisia sibiricum is weighed and crushed into coarse particles, 9-11 times the amount of water is added, and the mixture is soaked for 11-13 hours, 1.2-1.8 g of serine protease is added, and the mixture is heated in a water bath at 78-82° C. for 14-16 minutes, and then boiled for 45-55 minutes. After filtering, 1% glacial acetic acid solution is added to the aqueous solution to adjust the pH value to 3-4, and the mixture is allowed to stand for 9-11 hours, filtered, and the filtrate is separated on a macroporous resin column, and eluted with 90-110 mL of 75-85% ethanol, and the eluate is collected and concentrated under reduced pressure to an extract with a relative density of 1.15-1.25 at 50° C., thereby obtaining an Artemisia sibiricum extract for later use.

5. The method for preparing the pollen antipruritic and analgesic preparation according to claim 4, characterized in that: In the step (2), 35 g of Artemisia sibiricum is weighed and crushed into coarse particles, 10 times the amount of water is added, and the mixture is soaked for 12 hours, 1.5 g of serine protease is added, and the mixture is heated in a water bath at 80° C. for 15 minutes, and then boiled for 50 minutes. After filtering, 1% glacial acetic acid solution is added to the aqueous solution to adjust the pH value to 3-4, and the mixture is allowed to stand for 10 hours and filtered. The filtrate is separated on a macroporous resin column and eluted with 100 mL of 80% ethanol. The eluate is collected and concentrated under reduced pressure to an extract with a relative density of 1.1-1.3 at 50° C., thereby obtaining an Artemisia sibiricum extract for later use.

6. The method for preparing the pollen antipruritic and analgesic preparation according to claim 1, characterized in that: In the step (3), 45 g of Radix Trichosanthis is weighed, crushed into coarse particles, mixed, and soaked in 2 times the amount of 75% ethanol for 2 hours. The mixture is then refluxed and extracted with 75% ethanol at 40°C for two times, the first time for 3 hours and the second time for 1 hour. The two extracts are combined and filtered to obtain the Radix Trichosanthis extract for later use.

7. The method for preparing the pollen antipruritic and analgesic preparation according to claim 1, characterized in that: In the step (4), 20 g of frankincense and 20 g of myrrh are weighed, crushed into fine powder, and volatile oil is extracted with water vapor to obtain volatile oil and medicinal residues respectively, and the volatile oil is reserved; the medicinal residues are ultrasonically extracted twice with 2 times the amount of 95% ethanol, each time for 60 minutes, and the extracts are combined and filtered to obtain a mixed extract of frankincense and myrrh, which is reserved.

8. The method for preparing the pollen antipruritic and analgesic preparation according to claim 1, characterized in that: In the step (6), 5 g of borneol, 5 g of camphor, 20 g of peppermint oil and 5 g of eucalyptus oil are weighed and ground. After grinding evenly, the volatile oil obtained in step (4) is added and mixed evenly to obtain product B.

9. The method for preparing the pollen antipruritic and analgesic preparation according to claim 1, characterized in that: In the step (7), 80-120 mL of distilled water is taken and heated to 65-75° C., 8-12 g of methyl cellulose and 12-18 g of diglycerol dioleate are added, and stirred for 55-65 min at a stirring speed of 1000 r / min; 4.5-5.5 g of ascorbic acid is added, and stirred for 25-35 min at a stirring speed of 500 r / min; product B is added under a heat preservation state of 42-48° C., and stirred at a speed of 500 r / min, and cooled overnight; product A and 1 g of trichlorobutanol are added at room temperature, and stirred for 18-22 min at a stirring speed of 500 r / min, and distilled water is added to make up to 200-300 mL, sterilized, and potted to obtain the pollen antipruritic and analgesic preparation.

10. The method for preparing the pollen antipruritic and analgesic preparation according to claim 9, characterized in that: In the step (7), 100 mL of distilled water is heated to 70° C., 10 g of methyl cellulose and 15 g of diglycerol dioleate are added, and the mixture is stirred for 60 min at a stirring speed of 1000 r / min; 5 g of ascorbic acid is added, and the mixture is stirred for 30 min at a stirring speed of 500 r / min; product B is added under a 45° C. insulation state, and the mixture is stirred at a stirring speed of 500 r / min, and the mixture is cooled overnight; product A and 1 g of trichlorobutanol are added at room temperature, and the mixture is stirred for 20 min at a stirring speed of 500 r / min, and the volume is fixed to 250 mL with distilled water, sterilized, and potted to obtain a pollen antipruritic and analgesic preparation.

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