Pharmaceutical preparation for external treatment of neonatal jaundice and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to an external treatment pharmaceutical preparation for neonatal jaundice and a preparation method thereof. The external treatment medicinal preparation for neonatal jaundice comprises the following raw materials in parts by weight: 14-28 parts of oriental wormwood, 12-23 parts of scabiosa, 9-18 parts of ficus sarmentosa, 6-15 parts of potentilla discolor, 5-13 parts of poria cocos, 3-10 parts of astragalus membranaceus, 2-6 parts of immature bitter orange and 3-7 parts of liquorice. Test results show that the external treatment pharmaceutical preparation for the neonatal jaundice, which is prepared by the invention, can be smeared on the planta pedis of the neonatal, so that the total serum bilirubin level of each group of child patients can be remarkably reduced, and the total cure rate of clinical treatment is improved, and therefore, the external treatment pharmaceutical preparation has a remarkable treatment effect on the neonatal jaundice and has a wide application prospect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine, and particularly relates to a new-born jaundice external treatment drug preparation and a preparation method thereof. BACKGROUND

[0002] In medicine, the jaundice of new-borns within 28 days after birth is called neonatal jaundice. The disease refers to a common disease that the skin, mucosa and sclera appear yellow due to the increase of bilirubin level in blood caused by abnormal metabolism of bilirubin in the new-born period. Neonatal jaundice is one of the most common problems in the new-born period, which can be divided into physiological and pathological types. About 60%-70% of full-term infants and nearly 100% of premature infants can have physiological jaundice, which is usually self-limiting. However, if the bilirubin level is too high or increases too fast, physiological jaundice can progress to pathological jaundice, which often indicates the presence of potential causes or risks. The causes are complex and diverse, and if not timely and effective intervention, the high bilirubin can penetrate the immature blood-brain barrier and deposit in the brain tissue, causing bilirubin encephalopathy, which can cause serious neurological sequelae or even life-threatening.

[0003] The current clinical treatment methods include blue light irradiation and blood exchange therapy. Although blue light irradiation is widely used for mild symptoms, it is only a symptomatic and palliative method. Blood exchange can effectively reduce bilirubin, but the operation conditions are high, and it may cause serious adverse reactions, so the indications need to be strictly controlled. Drug therapy such as albumin and phenobarbital also has certain limitations. Although there is a practice of using Yinzhihuang oral liquid to treat the disease in traditional Chinese medicine, the drug is an adult preparation, which lacks safety and clinical trial data for new-borns, and direct use in new-borns has a great safety risk.

[0004] According to medical classics, delphinium is used for clearing heat, removing dampness and reducing yellow, and is traditionally used for liver and gallbladder dampness syndrome. However, the gastrointestinal function of new-borns is not fully developed, and the liver enzyme system is not mature, so oral administration can easily cause vomiting and unstable absorption, and increase the metabolic burden. At the same time, butter is often used for skin care or nutritional supplementation in new-borns, which is rich in lipid components and has good skin affinity and penetration-promoting effect, and can be used as an ideal external drug carrier.

[0005] Based on the above background, in order to explore a safer and more suitable treatment scheme for the new-born population, the present application provides a local drug preparation suitable for external use in new-borns, which is safe and convenient and has the potential to regulate bilirubin metabolism. SUMMARY

[0006] The first object of the present application is to provide a new-born jaundice external treatment drug preparation.

[0007] The second object of the present application is to provide a preparation method of the new-born jaundice external treatment drug preparation.

[0008] In order to achieve the above object, the technical scheme adopted by the present application is: A new-born jaundice external treatment drug preparation, comprising the following raw materials in weight parts: 14-28 parts of Herba Artemisiae Scopariae, 12-23 parts of Herba Viola, 9-18 parts of Ficus Elastica, 6-15 parts of Potentilla Discolor, 5-13 parts of Poria cocos, 3-10 parts of Astragalus membranaceus, 2-6 parts of Fructus Aurantii Immaturus, and 3-7 parts of Radix Glycyrrhizae.

[0009] Further, the following raw materials in weight parts are included: 21 parts of Herba Artemisiae Scopariae, 17 parts of Herba Viola, 13 parts of Ficus Elastica, 10 parts of Potentilla Discolor, 9 parts of Poria cocos, 6 parts of Astragalus membranaceus, 4 parts of Fructus Aurantii Immaturus, and 5 parts of Radix Glycyrrhizae.

[0010] According to the preparation method of the new-born jaundice external treatment drug preparation described above, the preparation method comprises the following steps: (1) The raw materials, Herba Artemisiae Scopariae, Herba Viola, Ficus Elastica, Potentilla Discolor, Poria cocos, Astragalus membranaceus, Fructus Aurantii Immaturus, and Radix Glycyrrhizae, are weighed in parts by weight, crushed, and sieved to prepare traditional Chinese medicine powder for use; (2) The traditional Chinese medicine powder prepared in step (1) is soaked in water and then decocted; the first filtrate and the first filter residue are collected after filtration and centrifugation; (3) Then, the first filter residue is soaked in water and then decocted; the second filtrate is collected after filtration and centrifugation, and the first filtrate and the second filtrate are combined and concentrated into extract; yellow butter is heated and added to the extract for stirring, and then cooled to room temperature to obtain the product.

[0011] Further, the mesh size of the sieving in step (1) is 70-90.

[0012] Further, the amount of water added in step (2) is 8-10 times the total weight of the traditional Chinese medicine powder; the soaking time is 1-3 h; and the decoction time is 3-5 h.

[0013] Further, the amount of water added in step (3) is 6-8 times the total weight of the traditional Chinese medicine powder; the soaking time is 0.5-1.5 h; the decoction time is 2-4 h; and the amount of yellow butter added is 10% of the mass of the extract.

[0014] Further, the concentration temperature in step (3) is 55-60℃, and the concentration is performed to a thick extract with a relative density of 1.10-1.30.

[0015] In order to more easily understand the present application, the efficacy of each raw material in the present application is described herein: Herba Artemisiae Scopariae: bitter, pungent, and slightly cold in nature, and returns to the spleen, stomach, liver, and gallbladder channels. It has the functions of clearing damp-heat and promoting bile discharge to treat jaundice. The Shennong's Herbal Classic records that it is used to treat wind-cold-damp-heat evil and heat accumulation in jaundice.

[0016] Blue basin flower: sweet, slightly bitter, cool. Liver, gallbladder meridian. Function and treatment: clearing heat and resolving toxicity, protecting liver and benefiting gallbladder, detumescence and analgesia. The Chinese Herbal Medicine: Mongolian Medicine Volume records: for lung heat, liver heat, throat heat and other diseases.

[0017] Climbing fig: slightly bitter, astringent, flat. Liver, spleen meridian. Function and treatment: dispelling wind and dampness, promoting blood circulation. The National Chinese Herbal Medicine Compilation records: treating rheumatic arthralgia or neuralgia, contusion and injury, indigestion, deficiency of qi and blood.

[0018] Turn white grass: sweet, slightly bitter, flat. Liver, stomach, large intestine meridian. Function and treatment: clearing heat and purging fire, cooling blood and stopping bleeding. The Easy-to-read Herbal records: clearing the intestines and stomach, removing wind and dampness.

[0019] Tuckahoe: sweet, light, flat. Heart, lung, spleen, kidney meridian. Function and treatment: benefiting spleen and stomach, calming heart and soothing spirit. The Shennong Herbal records: treating chest and lateral reverse qi, benefiting urination, long-term consumption of soul and spirit, and not hungry for long life.

[0020] Radix Astragali: sweet, warm. Lung, spleen meridian. Function and treatment: tonifying qi and consolidating the exterior, expelling pus and promoting tissue regeneration, and diuresis and detumescence. The Herbal records: tonifying qi, consolidating the exterior, and purging fire.

[0021] Hovenia dulcis Thunb: bitter, pungent, sour, slightly cold. Spleen, stomach meridian. Function and treatment: breaking qi and resolving accumulation, resolving phlegm and dissipating mass, regulating various drugs, leading drugs into channels, and expelling pathogenic factors. The Herbal records: invigorating the spleen, opening the stomach, regulating five zang organs, promoting digestion, and stopping vomiting.

[0022] Glycyrrhiza: sweet, flat. Heart, lung, spleen, stomach meridian. Function and treatment: tonifying spleen and qi, clearing heat and resolving toxicity, regulating various drugs.

[0023] The Herbal records: among various drugs, licorice is the monarch, treating seventy-two kinds of milk stone toxicity, resolving one thousand two hundred plant toxicity, regulating various drugs, and therefore has the title of "national old man".

[0024] Compared with the prior art, the beneficial effects of the present application mainly lie in: This invention provides a topical treatment preparation for neonatal jaundice. The preparation uses *Artemisia capillaris* and *Indigofera tinctoria* as the principal ingredients, which have the effects of clearing heat and detoxifying, promoting bile secretion and reducing jaundice. *Ficus pumila* and *Potentilla discolor* are used as assistant ingredients, which have the effects of promoting qi and blood circulation, cooling blood and reducing swelling, and ensuring smooth flow of qi and blood. *Poria cocos* and *Astragalus membranaceus* are used as adjuvant ingredients, which have the effects of tonifying the middle energizer and regulating the spleen and stomach. *Fructus Aurantii Immaturus* and *Radix Glycyrrhizae* are used as guiding ingredients. The components work synergistically to clear heat, reduce inflammation, detoxify, purge fire, cool blood, promote diuresis, eliminate dampness, dispel wind, and reduce swelling, and can be used to treat jaundice caused by damp-heat in the liver and gallbladder. Experimental results show that applying the topical treatment preparation prepared in this invention to the soles of newborns can significantly reduce the serum total bilirubin level in all groups of infants, improve the overall cure rate of clinical treatment, and thus have a significant therapeutic effect on neonatal jaundice. Furthermore, it overcomes the problem of difficulty in administering oral medications to newborns, has a simple preparation method, readily available raw materials, low cost, good therapeutic effect, and broad market prospects. Detailed Implementation

[0025] The technical solution of the present invention will be further described below with reference to specific embodiments. However, those skilled in the art should understand that the following embodiments are only for illustrating the present invention and should not be regarded as limiting the present invention. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the reagents or instruments used are all conventional products obtained through commercial channels.

[0026] Example 1: A topical treatment preparation for neonatal jaundice comprises the following raw materials in parts by weight: 21 parts Artemisia capillaris, 17 parts Sedum morganianum, 13 parts Ficus pumila, 10 parts Agrimonia pilosa, 9 parts Poria cocos, 6 parts Astragalus membranaceus, 4 parts Citrus aurantium, and 5 parts Glycyrrhiza uralensis.

[0027] A method for preparing a topical treatment drug for neonatal jaundice, the method comprising the following steps: (1) Weigh out each raw material according to the following weight proportions: 21 parts Artemisia capillaris, 17 parts Sedum spectabile, 13 parts Ficus benjamina, 10 parts Agrimonia pilosa, 9 parts Poria cocos, 6 parts Astragalus membranaceus, 4 parts Citrus aurantium, and 5 parts Glycyrrhiza uralensis. After crushing, pass through an 80-mesh sieve to obtain Chinese medicine powder for later use. (2) Soak the Chinese medicine powder prepared in step (1) in water equal to 9 times the total weight of the Chinese medicine powder for 2 hours, then decoct for 4 hours; filter, centrifuge, and collect the first filtrate and the first filter residue; (3) Then, add water equal to 7 times the total weight of the Chinese medicine powder to the first filter residue and soak for 1.0 h, then decoct for 3 h; after filtration and centrifugation, collect the second filtrate, and combine the first and second filtrates; concentrate under reduced pressure at a temperature of 57℃ and a pressure of -0.1MPa to obtain an extract with a relative density of 1.20; heat butter in a 60℃ water bath until melted, add it to the extract and stir well, wherein the amount of butter added is 10% of the mass of the extract, and cool to room temperature to obtain a topical treatment drug preparation for neonatal jaundice.

[0028] Implementation 2: A topical treatment drug preparation for neonatal jaundice, comprising the following raw materials in parts by weight: 14 parts Artemisia capillaris, 12 parts Sedum sarmentosum, 9 parts Ficus pumila, 6 parts Agrimonia pilosa, 5 parts Poria cocos, 3 parts Astragalus membranaceus, 2 parts Citrus aurantium, and 3 parts Glycyrrhiza uralensis.

[0029] A method for preparing a topical treatment drug for neonatal jaundice, the method comprising the following steps: (1) Weigh out each raw material according to the following weight proportions: 14 parts Artemisia capillaris, 12 parts Sedum spectabile, 9 parts Ficus benjamina, 6 parts Agrimonia pilosa, 5 parts Poria cocos, 3 parts Astragalus membranaceus, 2 parts Citrus aurantium, and 3 parts Glycyrrhiza uralensis. After crushing, pass through a 70-mesh sieve to obtain Chinese medicine powder for later use. (2) Soak the Chinese medicine powder prepared in step (1) in water equal to 8 times the total weight of the Chinese medicine powder for 1 hour, then decoct for 3 hours; filter, centrifuge, and collect the first filtrate and the first filter residue; (3) Then add water equal to 6 times the total weight of the Chinese medicine powder to the first filter residue and soak for 0.5 h, then decoct for 2 h; after filtration and centrifugation, collect the second filtrate and combine the first and second filtrates; concentrate under reduced pressure at a temperature of 55℃ and a pressure of -0.1MPa to concentrate to an extract with a relative density of 1.10; take butter and heat it to melt in a water bath at 60℃, add it to the extract and stir to mix well, wherein the amount of butter added is 10% of the mass of the extract, cool to room temperature, and a topical treatment drug preparation for neonatal jaundice is obtained.

[0030] Example 3: A topical treatment preparation for neonatal jaundice comprises the following raw materials in parts by weight: 28 parts Artemisia capillaris, 23 parts Sedum morganianum, 18 parts Ficus pumila, 15 parts Agrimonia pilosa, 13 parts Poria cocos, 10 parts Astragalus membranaceus, 6 parts Citrus aurantium, and 7 parts Glycyrrhiza uralensis.

[0031] A method for preparing a topical treatment drug for neonatal jaundice, the method comprising the following steps: (1) Weigh out each raw material according to the following weight proportions: 28 parts Artemisia capillaris, 23 parts Sedum morganianum, 18 parts Ficus lyrata, 15 parts Agrimonia pilosa, 13 parts Poria cocos, 10 parts Astragalus membranaceus, 6 parts Citrus aurantium, and 7 parts Glycyrrhiza uralensis. After crushing, pass through a 90-mesh sieve to obtain Chinese medicine powder for later use. (2) Soak the Chinese medicine powder prepared in step (1) in water equal to 10 times the total weight of the Chinese medicine powder for 3 hours, then decoct for 5 hours; filter, centrifuge, and collect the first filtrate and the first filter residue; (3) Then add water equal to 8 times the total weight of the Chinese medicine powder to the first filter residue and soak for 1.5 hours, then decoct for 4 hours; after filtration and centrifugation, collect the second filtrate and combine the first and second filtrates; concentrate under reduced pressure at a temperature of 60℃ and a pressure of -0.1MPa to obtain an extract with a relative density of 1.30; heat butter in a 60℃ water bath until melted, add it to the extract and stir well, wherein the amount of butter added is 10% of the mass of the extract, and cool to room temperature to obtain a topical treatment drug preparation for neonatal jaundice.

[0032] Comparative Example 1: The difference between Comparative Example 1 and Example 1 is that the Ficus benjamina var. chinensis in a topical treatment drug for neonatal jaundice is omitted, while all other aspects are the same as in Example 1.

[0033] Comparative Example 2: The difference between Comparative Example 2 and Example 1 is that the ingredient of a topical treatment for neonatal jaundice, Agrimonia pilosa, is omitted; otherwise, they are the same as in Example 1.

[0034] Experimental Example 1: This study aimed to evaluate the efficacy of a topical treatment for neonatal jaundice. A total of 100 eligible neonates with jaundice (aged 3-20 days, weighing 2500-4000g) were included. They were randomly assigned to four groups (Example 1, Example 2, Example 3, Comparative Example 1, and Comparative Example 2), with 20 infants in each group. Venous blood samples were collected from the neonates before treatment initiation and 3 days after treatment. Serum total bilirubin concentration was measured using an automated biochemical analyzer as the primary efficacy indicator. The treatment method involved applying 0.2g of the corresponding topical treatment for neonatal jaundice to the soles of the newborns twice daily for 3 consecutive days. During the treatment period, all neonates received standard neonatal care. After treatment, changes in jaundice of the skin, mucous membranes, and sclera were observed, and clinical efficacy was assessed according to the criteria in Table 1. The bilirubin levels of neonatal jaundice patients in each group before and after treatment are shown in Table 2; the total cure rate of neonatal jaundice patients in each group is shown in Table 3.

[0035] Table 1. Criteria for judging clinical efficacy: ; Table 2. Bilirubin levels before and after treatment in neonatal jaundice patients in each group: ; The results are shown in Table 2, which presents the bilirubin levels before and after treatment in each group of neonatal jaundice patients. As can be seen from Table 2, compared with Comparative Examples 1 and 2, the topical jaundice treatment preparations obtained in Examples 1-3 of this invention significantly reduced the serum total bilirubin levels in each group of patients. This indicates that the topical jaundice treatment preparations prepared in this invention can promote bilirubin excretion, thereby having a significant therapeutic effect on neonatal jaundice.

[0036] Table 3. Overall cure rate of neonatal jaundice in each group: ; The results are shown in Table 3, which represents the overall cure rate for neonatal jaundice in each group. As can be seen from Table 3, compared with Comparative Examples 1 and 2, the topical treatment drug formulations for neonatal jaundice prepared in Examples 1-3 of this invention can significantly improve the overall cure rate in clinical treatment and have a significant therapeutic effect on neonatal jaundice.

[0037] In summary, this topical treatment for neonatal jaundice, when applied to the soles of the newborn's feet, may allow the medication to penetrate the blood vessels and rapidly enter the liver and gallbladder via blood circulation, effectively promoting bilirubin excretion. This, in turn, reduces the serum total bilirubin level in all groups of infants, improving the overall cure rate in clinical treatment. It provides a non-invasive and convenient adjunctive treatment option for clinical practice, and is particularly suitable for early intervention in mild hyperbilirubinemia.

[0038] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.

Claims

1. A topical treatment drug for neonatal jaundice, characterized in that, The ingredients include the following parts by weight: Artemisia capillaris 14-28 parts, Sedum sarmentosum 12-23 parts, Ficus benjamina 9-18 parts, Agrimonia pilosa 6-15 parts, Poria cocos 5-13 parts, Astragalus membranaceus 3-10 parts, Citrus aurantium 2-6 parts, and Glycyrrhiza uralensis 3-7 parts.

2. The topical treatment drug formulation for neonatal jaundice according to claim 1, characterized in that, The ingredients include the following parts by weight: Artemisia capillaris 21 parts, Sedum spectabile 17 parts, Ficus benjamina 13 parts, Agrimonia pilosa 10 parts, Poria cocos 9 parts, Astragalus membranaceus 6 parts, Citrus aurantium 4 parts, and Glycyrrhiza uralensis 5 parts.

3. A method for preparing a topical treatment drug formulation for neonatal jaundice according to any one of claims 1-2, characterized in that, The preparation method includes the following steps: (1) Weigh out each raw material according to the weight proportions: Artemisia capillaris, Sedum morganianum, Ficus benjamina, Potentilla chinensis, Poria cocos, Astragalus membranaceus, Citrus aurantium, Glycyrrhiza uralensis, pulverize and sieve to obtain Chinese medicine powder for later use; (2) Soak the Chinese medicine powder prepared in step (1) in water, then decoct it; filter, centrifuge, and collect the first filtrate and the first filter residue; (3) Then add water to the first filter residue and soak it, then boil it; after filtering and centrifuging, collect the second filtrate, combine the first filtrate and the second filtrate, and concentrate it into an extract; heat the butter, add it to the extract and stir, and cool it to room temperature to obtain the final product.

4. The method for preparing a topical treatment drug for neonatal jaundice according to claim 3, characterized in that, The mesh size of the sieve in step (1) is 70-90.

5. The method for preparing a topical treatment drug for neonatal jaundice according to claim 3, characterized in that, In step (2), the amount of water added is 8-10 times the total weight of the Chinese herbal powder; the soaking time is 1-3 hours; and the decoction time is 3-5 hours.

6. The method for preparing a topical treatment drug for neonatal jaundice according to claim 3, characterized in that, In step (3), the amount of water added is 6-8 times the total weight of the Chinese herbal powder; the soaking time is 0.5-1.5 hours; and the decoction time is 2-4 hours.

7. The method for preparing a topical treatment drug for neonatal jaundice according to claim 3, characterized in that, In step (3), the concentration temperature is 55-60℃, and the concentration is carried out to a thick paste with a relative density of 1.10-1.30; the amount of butter added is 10% of the mass of the paste.