Traditional Chinese medicine preparation for treating climacteric syndrome and preparation method thereof

Abstract

The invention relates to a traditional Chinese medicine preparation for treating climacteric syndrome and a preparation method of the traditional Chinese medicine preparation. Hippophae rhamnoides fruit oil comprises the following effective components in parts by weight: 80-150 parts of palmitic acid, 110-120 parts of palmitoleic acid, 90-110 parts of oleic acid, 0.9-1.3 parts of vitamin E, 0.2-0.5 part of total fatty acid, 90-110 parts of linoleic acid, 100-120 parts of alpha-linolenic acid, 12-18 parts of total flavonoids of hippophae rhamnoides fruits, 16-25 parts of total amino acid, 3-8 parts of alpha-tocopherol and 3-6 parts of ferulic acid. Through the improved enzymolysis process, the contents of vitamin E, total fatty acid, linoleic acid, alpha-linolenic acid, total flavonoids of hippophae rhamnoides, total amino acid, alpha-tocopherol and ferulic acid in the prepared hippophae rhamnoides fruit oil are obviously increased. The traditional Chinese medicine preparation soft capsule is feasible and reasonable in formula, simple and feasible in preparation process and wide in market application prospect.

Description

Technical Field

[0001] The invention discloses a traditional Chinese medicine preparation for treating menopausal syndrome and a preparation method thereof, belonging to the field of traditional Chinese medicine preparation technology. Background Art

[0002] Menopausal syndrome is a group of syndromes that occur during the transition period from reproductive period to non-reproductive period in women due to endocrine disorders caused by ovarian dysfunction. Clinically, common menopausal women are characterized by high gonadotropin and low estrogen, and their symptoms vary from individual to individual, such as chest tightness, irritability, irritability, palpitations, sweating, insomnia, joint pain, constipation, cold and dry vulva, irregular menstruation and other symptoms. Menopause lasts from before menopause to after menopause in women, with a total time of up to ten years, and menopausal symptoms may recur. Especially for my country's gradual move towards an aging society, the number of menopausal women mentioned above will increase year by year, and modern women pay more and more attention to personal physical and mental health. Therefore, it is of vital importance to develop a drug for the treatment of menopausal syndrome.

[0003] Although there are many Chinese patent medicines for treating menopausal syndrome on the market, most of them are compound preparations, and their dosage forms are mostly: tablets, hard capsules, pills, etc. The specific products involved are: Gengnianling Capsules, Gengnianan Tablets, Kunbao Pills, etc. The prescription of the Chinese medicine preparation of the present invention comes from Associate Researcher Wei Xiazhen. Based on the record of the blood-benefiting effect of seabuckthorn in "Jingzhu Materia Medica", it is speculated that the single prescription of seabuckthorn fruit oil may have the effect of regulating qi and blood, improving the effect of estrogen, and can be used for the treatment of women's menopausal syndrome. The Tiangui Gengnian soft capsule of the present invention is a soft capsule made of a single medicinal seabuckthorn fruit oil.

[0004] Through literature search, it was found that there are articles related to sea buckthorn oil soft capsules, Hu Xudong, Optimization of sea buckthorn oil degumming process and industrial production design of soft capsule products, Xinjiang Agricultural University, published on June 1, 2020. The capsule shell in this paper only uses purified water, glycerin and gelatin. Sea buckthorn oil is unstable to light and contains a large amount of fatty acids, which are easily oxidized and deteriorated. The soft capsule preparation method involved in this document does not involve sunscreens and preservatives. In addition, the increase in water content will accelerate the oxidation of gelatin, accelerate the aging of the capsule wall, and prolong the disintegration time. The use of plasticizers can reduce the penetration of oxygen into the capsule shell, thereby preventing the capsule wall from aging too quickly and improving the capsule disintegration.

[0005] The Chinese medicine preparation for menopausal syndrome of the present invention is Tiangui Gengnian soft capsule, the main component of which is seabuckthorn fruit oil. Its functions and indications are: nourishing liver and kidney, promoting blood circulation and removing blood stasis. It is used for menopausal syndrome of liver and kidney yin deficiency and blood stasis syndrome, and can improve symptoms such as hot sweating, irritability, insomnia, forgetfulness, dizziness, tinnitus, back and knee pain, chest tightness, hypochondriac pain, dry stool, skin itching, etc.

[0006] The applicant has combed through the technical development documents of the series of products of the seabuckthorn fruit oil, and found that CN1106691A discloses the use of seabuckthorn fruit oil in the preparation of medicines for regulating women's endocrine function (women's menopausal syndrome, premature ovarian failure, premenstrual syndrome and hyperthyroidism). CN1119114A discloses seabuckthorn flavonoids oral liquid, which adopts supercritical CO2 extraction of seabuckthorn flavonoids liquid, and its formula is: 8000 grams of seabuckthorn fruit, 150 grams of safflower, and 150 grams of licorice, which is prepared into seabuckthorn flavonoids oral liquid, which can effectively retain more active substances and is used to prevent and treat cardiovascular diseases, reduce cholesterol, reduce blood lipids, and reduce myocardial infarction. There is a significant effect. CN101705145A records a new method for separating and extracting seabuckthorn fruit oil, which uses a combination of bioengineering enzyme technology and microporous filtration technology to separate and extract seabuckthorn fruit oil, decompose pectin, protein, cellulose, hemicellulose, fat and other substances in seabuckthorn fruit, disperse the original nutrients of seabuckthorn fruit in the fruit pulp, and improve the quality of seabuckthorn juice. CN101810339A discloses a composite antioxidant edible soft capsule formula and a preparation method thereof. The soft capsule encapsulation liquid component is a mixture of sea buckthorn seed / fruit oil, lycopene, and tea polyphenols. The formula of the soft capsule encapsulation liquid is: 70%-90% sea buckthorn oil, 3%-20% lycopene, 0.1%-3% tea polyphenols, 4%-7% beeswax, and beeswax is a suspension. The present invention has strong antioxidant, anti-aging, immunity-enhancing, and blood lipid-lowering effects. CN106404944A discloses a quality detection method for sea buckthorn fruit oil. The method uses gas chromatography to determine the content of palmitic acid and palmitoleic acid in sea buckthorn fruit oil. The method can accurately detect the content of the two components in sea buckthorn fruit oil and ensure the quality of its raw materials.

[0007] Seabuckthorn is a plant that is both a medicine and food. Its fruit oil contains various nutritional and health care ingredients such as flavonoids, carotene, vitamins, and unsaturated fatty acids. At present, the seabuckthorn fruit oil and seabuckthorn fruit oil soft capsules on the market, and the seabuckthorn fruit oil is made into soft capsules, which has broad development prospects. The applicant found in the process improvement research and clinical application process of Tiangui Menopause Soft Capsules that the effective substance enrichment degree of seabuckthorn fruit oil in the product is not high, and there is also seabuckthorn fruit oil that is unstable to light, and contains a large amount of fatty acid substances, which is easy to oxidize and deteriorate. In addition, the increase of capsule shell moisture will accelerate the oxidation of gelatin, accelerate the aging of capsule wall, and cause many problems of extended disintegration time. Therefore, it is quite necessary to develop a Chinese medicine preparation with higher effective ingredient content and better preparation stability. Summary of the invention

[0008] The purpose of the present invention is to provide a Chinese medicine preparation for treating menopausal syndrome and a preparation method thereof. The Chinese medicine preparation has the advantage of high enrichment of effective substance components. Another purpose of the present invention is to provide a method for preparing a Chinese medicine preparation soft capsule material with good stability. In the preparation method of the soft capsule material, an appropriate amount of sunscreen red iron oxide, a preservative ethyl hydroxybenzoate and a plasticizer sorbitol are added to prevent the photosensitive drug from being decomposed by light; it is beneficial to ensure the stability of the Chinese medicine preparation of the present invention and the exertion of clinical efficacy. It can be seen from this that the Chinese medicine preparation soft capsule formula ratio of the present invention is scientific and reasonable, the preparation process is simple and feasible, and it has broad market application prospects.

[0009] The technical solution of the patent application of this invention is:

[0010] A traditional Chinese medicine preparation for treating menopausal syndrome, wherein the effective substance of the traditional Chinese medicine preparation is seabuckthorn fruit oil, and the seabuckthorn fruit oil comprises the following effective ingredients in a proportion of: 80-150 parts of palmitic acid, 110-120 parts of palmitoleic acid, 90-110 parts of oleic acid, 0.9-1.3 parts of vitamin E, and 0.2-0.5 parts of total fatty acids.

[0011] Preferably, the sea buckthorn fruit oil includes the following effective ingredients in a dosage ratio: 80-150 parts of palmitic acid, 110-120 parts of palmitoleic acid, 90-110 parts of oleic acid, 0.9-1.3 parts of vitamin E, 0.2-0.5 parts of total fatty acids, 90-110 parts of linoleic acid, 100-120 parts of α-linolenic acid, 12-18 parts of total flavonoids of sea buckthorn, 16-25 parts of total amino acids, 3-8 parts of α-tocopherol, and 3-6 parts of ferulic acid.

[0012] Preferably, the sea buckthorn fruit oil includes the following active ingredients in a dosage ratio: 125 parts of palmitic acid, 115 parts of palmitoleic acid, 106 parts of oleic acid, 1.2 parts of vitamin E, and 0.35 parts of total fatty acids.

[0013] Preferably, the sea buckthorn fruit oil includes the following effective ingredients in a dosage ratio: 125 parts of palmitic acid, 115 parts of palmitoleic acid, 106 parts of oleic acid, 1.2 parts of vitamin E, 0.35 parts of total fatty acids, 100 parts of linoleic acid, 110 parts of α-linolenic acid, 16 parts of total flavonoids of sea buckthorn, 22 parts of total amino acids, 6 parts of α-tocopherol, and 5 parts of ferulic acid.

[0014] Preferably, the extraction and preparation process of the seabuckthorn fruit oil is:

[0015] Take seabuckthorn fruit, sort and wash it, wet-crush and pulp it in turn, add pectinase and cellulase (in a ratio of 1:1), enzymolysis time is 1.5-2.5 hours, enzyme dosage is 2-3% of the mass of seabuckthorn fruit, enzymolysis temperature is 40-50°C, vibration separation is performed to obtain seabuckthorn pulp, and the temperature is heated to 50±10°C, centrifuged, crude seabuckthorn fruit oil is collected, separated at a speed of 9000-11000rpm, heated at 50±5°C, filtered through a microporous filter at a pressure of 0.3Mpa-0.6Mpa, sterilized, filled with nitrogen, and filled to obtain the product.

[0016] As a further preferred embodiment of the present invention, the extraction and preparation process of seabuckthorn fruit oil is as follows:

[0017] Take seabuckthorn fruit, sort and wash it, wet-crush and pulp it in turn, add pectinase and cellulase (in a ratio of 1:1), enzymolysis time is 2 hours, enzyme dosage is 2.5% of the mass of seabuckthorn fruit, enzymolysis temperature is 4.5°C, vibration separation is performed to obtain seabuckthorn pulp, and the temperature is heated to 50±10°C, centrifuged, crude seabuckthorn fruit oil is collected, separated at a speed of 9000-11000 rpm, heated to 50±5°C, filtered through a microporous filter at a pressure of 0.4 MPa-0.5 MPa, sterilized, filled with nitrogen, and filled to obtain the product.

[0018] Preferably, the Chinese medicine preparation is a soft capsule preparation whose auxiliary material composition ratio is: 400-500 parts of seabuckthorn fruit oil, 150-190 parts of gelatin, 120-150 parts of purified water, 40-50 parts of glycerol, 20-30 parts of sorbitol, 2-3 parts of red iron oxide, and 0.1-0.5 parts of ethyl hydroxybenzoate.

[0019] Preferably, the Chinese medicine preparation is a soft capsule preparation whose auxiliary material composition ratio is: 450 parts of sea buckthorn fruit oil, 173 parts of gelatin, 135 parts of purified water, 45 parts of glycerol, 25 parts of sorbitol, 2.4 parts of red iron oxide, and 0.3 parts of ethylparaben.

[0020] As a further preference of the present invention, the preparation method comprises the following steps:

[0021] Step (1): weigh seabuckthorn fruit oil, stir at 35-43 rpm, mix for 25-35 minutes, and set aside;

[0022] Step (2): Weigh ethylparaben and red iron oxide, add purified water to mix, add to a colloid mill, grind for 15 to 25 minutes, and collect the mixed solution;

[0023] Step (3): Take sorbitol, add purified water and stir evenly;

[0024] Step (4): Mix the ethyl hydroxybenzoate and red iron oxide mixture of step (2), the sorbitol solution of step (3), and glycerin, stir at a stirring speed of 45 to 55 rpm for 15 to 25 minutes to mix them evenly, then take gelatin, control and maintain the temperature at 80±5°C to dissolve and mix them evenly, adjust the vacuum degree to -0.06 to -0.07MPa, evacuate for 20 to 40 minutes, observe that there are no bubbles in the glue solution, evacuate statically for 10 to 15 minutes, pressurize the glue solution, pass it through a 60-mesh sieve, heat it to 60±5°C for insulation, input the gelatin into a pilling machine, apply a film, fill it with the seabuckthorn fruit oil solution of step (1), press the soft capsule, shape and dry it, select the pills, and you are done.

[0025] The present invention is based on the Tiangui Menopause technology and is carried out during a large amount of scientific research. The optimal key step parameters of the seabuckthorn fruit oil extraction process are accidentally found, so that the effective ingredients in the seabuckthorn fruit oil are increased, and the formula and preparation process of the soft capsule preparation are optimized to improve the stability of the product.

[0026] In order to further reflect the innovativeness of the preparation process technology of the present invention, a large number of previous process research and screening schemes are now organized as follows:

[0027] 1.1 Existing extraction and preparation technology of sea buckthorn fruit oil

[0028] The seabuckthorn berries are picked, cleaned, wet crushed and pulped in sequence, separated, separated by horizontal screw, and separated by vibration to obtain seabuckthorn berry pulp, which is heated to (50±10°C), centrifuged, and the crude seabuckthorn berry oil is collected, separated by a tubular centrifuge (9000-11000rpm), heated (50±5°C), filtered by a microporous filter at a pressure of 0.3mpa-0.6mpa, sterilized, filled with nitrogen, and bottled.

[0029] 1.2 Enzyme type screening

[0030] Effect of enzyme types on the extraction rate of seabuckthorn fruit oil

[0031] The present invention adopts biological enzyme technology to catalyze the reaction of seabuckthorn fruit, which can degrade cellulose, hemicellulose and other substances in the seabuckthorn fruit, make the nutrition and health care components of the seabuckthorn fruit quickly seep into the fruit pulp, and increase the content of effective components of seabuckthorn fruit oil.

[0032] Table 1 Effect of enzyme types on extraction rate of seabuckthorn oil

[0033]

[0034] From the experimental results in Table 1, it can be seen that the extraction rate of sea buckthorn oil is significantly improved after adding pectinase, cellulase and compound enzyme treatment.

[0035] 1.3 Optimization of seabuckthorn fruit oil enzyme extraction process

[0036] On the basis of single factor experiment, orthogonal experimental design was adopted, with A enzymatic hydrolysis time, B enzyme dosage and enzymatic hydrolysis temperature as the investigation factors.

[0037] Table 2 Orthogonal test factor level table

[0038]

[0039] The optimal enzymatic hydrolysis time, B enzyme dosage and enzymatic hydrolysis temperature obtained by single factor experiment were used as extraction conditions, and the yield of sea buckthorn oil was used as an indicator. A total of 9 experiments with 3 factors and 3 levels were designed. The results are shown in Table 3.

[0040] Table 3 Orthogonal test results

[0041]

[0042]

[0043] From the results in Table 3 above, it can be seen that the optimal combination is A2B3C2, that is, the enzymatic hydrolysis time is 2 hours, the enzyme dosage is 2.5%, and the enzymatic hydrolysis temperature is 45° C. The extraction rate of sea buckthorn fruit oil prepared by the optimized process is 78.8%.

[0044] According to the extraction process of seabuckthorn fruit oil under 1.1 of the present invention, and according to the optimized parameters of the seabuckthorn fruit oil enzyme extraction process under 1.2, the enzymatic hydrolysis time is 2 hours, the enzyme dosage is 2.5%, and the enzymatic hydrolysis temperature is 45° C., the content of the effective substance components of the seabuckthorn fruit oil raw material is as follows:

[0045] The contents of effective components in the seabuckthorn fruit oil of the present invention (original process) are determined as follows: palmitic acid 21.5%, palmitoleic acid 18.7%, oleic acid 19.4%, vitamin E 0.26%, total fatty acids 5.9%, linoleic acid 5.7%, α-linolenic acid 5.8%, total flavonoids of seabuckthorn 1.1%, total amino acids 1.7%, α-tocopherol 0.7%, ferulic acid 0.6%, and the remainder is other effective components.

[0046] The content of effective components in the seabuckthorn fruit oil (after improved enzymatic hydrolysis process) of the present invention is determined as follows: palmitic acid 23.2%, palmitoleic acid 24.1%, oleic acid 21.7%, vitamin E 0.52%, total fatty acids 6.3%, linoleic acid 6.2%, α-linolenic acid 5.8%, total flavonoids of seabuckthorn 3.5%, total amino acids 4.3%, α-tocopherol 1.5%, ferulic acid 1.1%, and the remainder is other elements, and the remainder is other effective components.

[0047] After the improved enzymatic hydrolysis process, the prepared sea buckthorn fruit oil has significantly increased contents of vitamin E, total fatty acids, linoleic acid, α-linolenic acid, total sea buckthorn flavonoids, total amino acids, α-tocopherol and ferulic acid, thereby increasing its health benefits.

[0048] 1.4 Screening of the preparation process of the soft capsule shell of the present invention

[0049] The molding quality of the capsule shell (the hardness and elasticity of the capsule shell) is the key link in whether the quality of the preparation process of Tiangui Gengnian soft capsule is reasonable or not. The research design fixed the ratio of gelatin to water, the ratio of gelatin to glycerol, the ratio of glycerol to sorbitol, the ratio of gelatin to water, and the thickness of the pill film. The screening results are shown in Table 4, Table 5, Table 6, and Table 7.

[0050] Table 4 Comparison of different ratios of gelatin to water

[0051]

[0052] The experimental results in Table 4 show that the ratio of gelatin to water is 1:0.80 after screening, and the preparation process ratio is reasonable.

[0053] Table 5 Comparison of different ratios of gelatin and glycerol

[0054]

[0055] The results in Table 5 show that the ratio of gelatin to glycerol is 1:0.25 after screening, and its preparation process ratio is reasonable.

[0056] Table 6 Comparison of different ratios of glycerol and sorbitol

[0057]

[0058]

[0059] The results in Table 6 show that after screening, the ratio of glycerol to sorbitol is 1:0.55, and the preparation process ratio is reasonable.

[0060] Table 7 Comparison of different film thickness and filler dosage

[0061]

[0062] The results in Table 7 show that the thickness of the film coating is closely related to the dosage accuracy of the capsule contents. The thickness of the coated film is 0.95 mm, the contents are filled up to the standard, the appearance quality is good, and the process is reasonable.

[0063] 1.4.1 Determine the composition of Tiangui Gengnian soft capsules

[0064] Tiangui Gengnian soft capsule is a soft capsule filled with seabuckthorn fruit oil, which is convenient for transportation, storage and use. The soft capsule can not only avoid the leakage of oily drugs, but also improve the bioavailability of the preparation. After a series of experimental studies, it was determined that when preparing the capsule material, the auxiliary material ratio of gelatin to water is 1:0.8; the ratio of gelatin to glycerol is 1:0.25; the ratio of glycerol to sorbitol is 1:0.55; and the capsule shell thickness is 0.95mm. This ratio of capsule material can ensure the elasticity and water content of the soft capsule material, ensure the disintegration time, and ultimately ensure the absorption and utilization of the effective ingredients of the seabuckthorn fruit oil of the present invention.

[0065] Beneficial effects of the Chinese medicine preparation of the present invention:

[0066] ⑴. After a large number of experimental studies and explorations, the present invention finally found a Chinese medicine preparation prescription composition and ratio for menopausal syndrome with high enrichment of effective substance components. The seabuckthorn fruit oil includes the following effective ingredients in a ratio of dosage: 80-150 parts of palmitic acid, 110-120 parts of palmitoleic acid, 90-110 parts of oleic acid, 0.9-1.3 parts of vitamin E, 0.2-0.5 parts of total fatty acids, 90-110 parts of linoleic acid, 100-120 parts of α-linolenic acid, 12-18 parts of total flavonoids of seabuckthorn, 16-25 parts of total amino acids, 3-8 parts of α-tocopherol, and 3-6 parts of ferulic acid. After the improved enzymatic hydrolysis process, the prepared seabuckthorn fruit oil has a significant increase in the content of vitamin E, total fatty acids, linoleic acid, α-linolenic acid, total flavonoids of seabuckthorn, total amino acids, α-tocopherol, and ferulic acid components to increase its health care effect.

[0067] (2) The present invention also provides a method for preparing a Chinese medicine soft capsule material with good stability, wherein the auxiliary material composition ratio is: 400-500 parts of seabuckthorn fruit oil, 150-190 parts of gelatin, 120-150 parts of purified water, 40-50 parts of glycerol, 20-30 parts of sorbitol, 2-3 parts of red iron oxide, and 0.1-0.5 parts of ethyl hydroxybenzoate. The optimal ratio after optimization is: 450 parts of seabuckthorn fruit oil, 173 parts of gelatin, 135 parts of purified water, 45 parts of glycerol, 25 parts of sorbitol, 2.4 parts of red iron oxide, and 0.3 parts of ethyl hydroxybenzoate.

[0068] The present invention adds an appropriate amount of sunscreen red iron oxide, preservative ethyl hydroxybenzoate and plasticizer sorbitol in the preparation method of the soft capsule material, which is beneficial to preventing photosensitive drugs from being decomposed by light; ensuring the effectiveness and quality controllability of the drug; and ensuring the stability of the Chinese medicine preparation of the present invention and the exertion of clinical efficacy; and providing patients with more stable and reliable drugs. The present invention prepares soft capsules (also known as capsules), which are suitable for filling oily liquid drugs or oily oil solutions. The main component of the Tiangui Gengnian soft capsule shell is gelatin, and plasticizers, humectants glycerol and sorbitol are added as appropriate, and a small amount of sunscreen and preservatives are added, which can protect the sea buckthorn fruit oil from being easily oxidized and deteriorated, and can reduce the penetration of oxygen to the capsule shell, thereby preventing the capsule wall from aging too quickly, improving the capsule disintegration, making the product quality more stable, and more conducive to the storage and preservation of the product after it is put on the market. The sea buckthorn fruit oil, the raw material of the Tiangui Gengnian soft capsule, is exposed to the air, is unstable to light, the color of the raw material changes slightly, the acid value and peroxide value increase slightly, and the vitamin E and total fatty acids decrease slightly.

[0069] The stability test data show that the present invention optimizes the soft capsule preparation process, can overcome the phenomenon that the content of the effective components in the seabuckthorn fruit oil of the present invention is not reduced by photolysis, improves the various indicators during the storage process to meet the specified requirements, ensures the stability of the preparation, and is beneficial to its intrinsic quality reliability.

[0070] ⑶. Animal pharmacology experiments have shown that the Chinese medicine preparations of Example 1 and Example 2 can significantly improve and increase the estradiol content in the serum of immature rats, and compared with distilled water, there is a significant difference (P<0.01). The Chinese medicine preparation of the present invention can improve the estradiol content in rats, which also shows that the Chinese medicine preparation of the present invention is used for the treatment of menopausal syndrome. DETAILED DESCRIPTION

[0071] In order to more fully understand the implementation of the present invention, the present invention is further described below through typical examples. The following and pharmacodynamics are used to prove the beneficial therapeutic effect of the Chinese medicine composition, wherein the Chinese medicine preparation for menopausal syndrome of the present invention is Tiangui Gengnian soft capsule. The following experiments are intended to illustrate the present invention rather than to limit the present invention.

[0072] Example 1

[0073] 1000g of seabuckthorn fruit are taken, sorted, cleaned, wet crushed and pulped in sequence, separated, separated by horizontal screw, and separated by vibration to obtain seabuckthorn fruit pulp, which is heated to 50°C, centrifuged, and crude seabuckthorn fruit oil is collected. The crude oil is separated by a tubular centrifuge at 9000-11000rpm, heated to 50°C, filtered through a microporous filter at a pressure of 0.3mpa-0.6mpa, sterilized, filled with nitrogen, and bottled.

[0074] Then take 450g seabuckthorn oil, 173g gelatin, 135g distilled water, 45g glycerin, 25g sorbitol, 2.4g red iron oxide, and 0.3g ethylparaben;

[0075] The soft capsule preparation method is as follows:

[0076] Step (1): weigh seabuckthorn fruit oil, stir at 35-43 rpm, mix for 25-35 minutes, and set aside;

[0077] Step (2): Weigh ethylparaben and red iron oxide, add purified water to mix, add to a colloid mill, grind for 15 to 25 minutes, and collect the mixed solution;

[0078] Step (3): Take sorbitol, add purified water and stir evenly;

[0079] Step (4): After mixing and stirring the ethyl hydroxybenzoate, red iron oxide mixed solution, sorbitol solution and glycerol in step (2), the stirring speed is 45-55 rpm, and the stirring time is 15-25 minutes to make it evenly mixed, then gelatin is taken, the temperature is controlled to be 80±5°C, so that it is dissolved and mixed evenly, the vacuum degree is adjusted to -0.06--0.07MPa, and vacuumization is carried out for 20-40 minutes. When the glue solution is observed to be bubble-free, static vacuumization is carried out for 10-15 minutes, the glue solution is pressurized, passed through a 60-mesh screen, heated to 60±5°C for insulation, gelatin is input into a pill making machine, a film is applied, the step (1) seabuckthorn fruit oil liquid is filled, soft capsules are pressed, the soft capsules are shaped and dried, and pills are selected. The filling pump of the pill making machine is adjusted to 0.5ml so that the filling amount of each capsule is 0.45g. The newly made capsules are conveyed to the drum dryer for drying, and then the liquid paraffin (lubricant for capsule pressing) adhering to the surface of the capsules is removed with 95% ethanol, and then the capsules are placed in a clean room at 25℃±2, RH40% for drying for 48 hours. After passing the inspection, they are packaged, sealed and stored in a cool place away from light.

[0080] Process yield = (output ÷ average weight of each soft capsule × 0.45 g / capsule) / sea buckthorn fruit oil feed amount × 100%; Material balance rate = (output + non-recyclable amount + rubber tailings) / feed amount × 100%, Note: 20 soft capsules are randomly selected from the cage-dried capsules to calculate the average capsule weight.

[0081] Example 2

[0082] 1000g of seabuckthorn fruit is taken, sorted, cleaned, wet-crushed and pulped in sequence, and then a composite enzyme (pectinase: cellulase 1:1) is added, the enzyme dosage is 2.5%, the enzymatic hydrolysis time is 2 hours, the enzymatic hydrolysis temperature is 45°C, separation, horizontal screw separation, vibration separation are performed to obtain seabuckthorn pulp, and the temperature is heated to (50±10°C), centrifuged, crude seabuckthorn fruit oil is collected, separated by a tubular centrifuge (9000-11000rpm), heated (50±5°C), filtered by a microporous filter at a pressure of 0.3MPa-0.6MPa, sterilized, filled with nitrogen, and filled to obtain the product.

[0083] Then take 450g of seabuckthorn fruit oil, 173g of gelatin, 135g of distilled water, 45g of glycerin, 25g of sorbitol, 2.4g of red iron oxide, and 0.3g of ethylparaben; the preparation method of soft capsules is the same as the preparation method in Example 1, and 1000 soft capsules are prepared, each weighing 0.45g.

[0084] Example 3

[0085] The preparation method is the same as that of Example 1 of the present invention, and the only changed soft capsule formula is: 500g seabuckthorn fruit oil, 150g gelatin, 150g purified water, 50g glycerin, 30g sorbitol, 2g red iron oxide, and 0.5g ethylparaben; the other parameters remain unchanged.

[0086] Example 4

[0087] The preparation method is the same as that of Example 1 of the present invention, and the only changed soft capsule formula is: 400g seabuckthorn fruit oil, 190g gelatin, 120g purified water, 40g glycerin, 20g sorbitol, 3g red iron oxide, and 0.1g ethylparaben; the other parameters remain unchanged.

[0088] Example 5

[0089] The preparation method is the same as that of Example 1 of the present invention, and the only changed soft capsule formula is: 450g seabuckthorn fruit oil, 170g gelatin, 130g purified water, 45g glycerol, 25g sorbitol, 2.5g red iron oxide, and 0.3g ethylparaben; the other parameters remain unchanged.

[0090] Experimental Example 1 Pharmacodynamics experiment of seabuckthorn fruit oil of the present invention

[0091] 1.1 Test methods

[0092] 40 immature female rats aged 1.5 to 2 months, weighing 100-150 g, were selected and divided into three groups, namely: a distilled water control group, a Chinese medicine preparation of Example 1 of the present invention (Comparative Example 1), and a Chinese medicine preparation of Example 2 of the present invention. The drug dosages of the present invention were 3.26 and 3.26 g / kg, respectively. Each group was intragastrically administered 3 times a day for 21 consecutive days. After the last administration, the rats were fasted for 12 hours, anesthetized by intraperitoneal injection of sodium pentobarbital, and blood was collected from the heart. The serum was separated and filtered, and the estradiol content in the rat serum was determined by radioimmunoassay.

[0093] Table 8 Effects on serum estradiol levels in female rats

[0094]

[0095] Note: Compared with the normal group, *P<0.01, compared with the control group, ▲ P<0.01.

[0096] As shown in the experimental results of Table 8, the Chinese medicine preparations of Example 1 and Example 2 of the present invention can significantly improve and increase the estradiol content in the serum of immature rats, and compared with distilled water, there is a significant difference (P<0.01). Animal experiments have verified that the Chinese medicine preparation of the present invention can improve the estradiol level in rats, which further illustrates the treatment for the treatment of menopausal syndrome.

[0097] Experimental Example 2: Stability Study of Tiangui Gengnian Soft Capsules of the Present Invention

[0098] 2.1 Lighting test results

[0099] Take an appropriate amount of samples from batch 20110101 and pack them into uncovered flat dishes (φ90mm), 20ml per dish (oil layer thickness 10mm), take 10 dishes, place them in a light kitchen with an illumination of 2000Lx (5 40w fluorescent lamps are arranged at intervals, height 70cm), and illuminate them continuously for 10 days (room temperature 18-22℃, relative humidity 45%-65% during the test period), take samples for testing on the 5th and 10th days, and compare with the results of day 0. The test results are shown in Table 9.

[0100] Table 9 Lighting test results

[0101]

[0102]

[0103]

[0104] The results showed that seabuckthorn oil was unstable to light when exposed to air. After 10 days of light exposure (2000Lx), the color changed slightly, the acid value and peroxide value increased slightly, the vitamin E and total fatty acids decreased slightly, and other indicators remained almost unchanged. This suggests that seabuckthorn oil should be stored in an air-tight and light-shielded environment.

[0105] 2.2 Study on the stability of the Chinese medicine preparation of the present invention

[0106] Three batches of homemade soft capsules were packaged in aluminum-plastic packaging and observed for 6 months under accelerated test (temperature 40°C ± 2°C, relative humidity 75% ± 5%). The stability results are shown in Tables 10, 11, and 12.

[0107] Table 10 Observation results of Tiangui Gengnian soft capsule accelerated test

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[0109]

[0110] Table 11 Observation results of Tiangui Gengnian soft capsule accelerated test

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[0114] Table 12 Observation results of Tiangui Gengnian soft capsule accelerated test

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Claims

1. A Chinese medicine preparation for treating menopausal syndrome, wherein the effective substance of the Chinese medicine preparation is seabuckthorn fruit oil, characterized in that: The seabuckthorn fruit oil comprises the following effective ingredients in a proportion of 80-150 parts of palmitic acid, 110-120 parts of palmitoleic acid, 90-110 parts of oleic acid, 0.9-1.3 parts of vitamin E and 0.2-0.5 parts of total fatty acids.

2. The Chinese medicine preparation according to claim 1, characterized in that: The seabuckthorn fruit oil includes the following effective ingredients in a proportion of 80-150 parts of palmitic acid, 110-120 parts of palmitoleic acid, 90-110 parts of oleic acid, 0.9-1.3 parts of vitamin E, 0.2-0.5 parts of total fatty acids, 90-110 parts of linoleic acid, 100-120 parts of α-linolenic acid, 12-18 parts of total flavonoids of seabuckthorn, 16-25 parts of total amino acids, 3-8 parts of α-tocopherol, and 3-6 parts of ferulic acid.

3. The Chinese medicine preparation according to claim 1, characterized in that: The sea buckthorn fruit oil includes the following effective ingredients in a dosage ratio: 125 parts of palmitic acid, 115 parts of palmitoleic acid, 106 parts of oleic acid, 1.2 parts of vitamin E, and 0.35 parts of total fatty acids.

4. The Chinese medicine preparation according to claim 2, characterized in that: The sea buckthorn fruit oil includes the following effective ingredients in a dosage ratio: 125 parts of palmitic acid, 115 parts of palmitoleic acid, 106 parts of oleic acid, 1.2 parts of vitamin E, 0.35 parts of total fatty acids, 100 parts of linoleic acid, 110 parts of α-linolenic acid, 16 parts of total flavonoids of sea buckthorn, 22 parts of total amino acids, 6 parts of α-tocopherol, and 5 parts of ferulic acid.

5. The Chinese medicine preparation according to claims 1 to 4, characterized in that: The extraction and preparation process of the seabuckthorn fruit oil is as follows: The seabuckthorn fruit is picked, cleaned, wet-crushed and pulped in turn, pectinase and cellulase are added in a ratio of 1:1, the enzymolysis time is 1.5-2.5 hours, the enzyme dosage is 2-3% of the mass of the seabuckthorn fruit, the enzymolysis temperature is 40-50°C, vibration separation is performed to obtain seabuckthorn pulp, and the temperature is heated to 50±10°C, centrifuged, crude seabuckthorn fruit oil is collected, separated at a speed of 9000-11000 rpm, heated at 50±5°C, filtered through a microporous filter at a pressure of 0.3 MPa-0.6 MPa, sterilized, filled with nitrogen, and filled to obtain the product.

6. The Chinese medicine preparation according to claims 1 to 4, characterized in that: The Chinese medicine preparation is a soft capsule preparation, and the auxiliary material composition ratio is: 400-500 parts of seabuckthorn fruit oil, 150-190 parts of gelatin, 120-150 parts of purified water, 40-50 parts of glycerol, 20-30 parts of sorbitol, 2-3 parts of red iron oxide, and 0.1-0.5 parts of ethyl hydroxybenzoate.

7. The Chinese medicine preparation according to claim 6, characterized in that: The Chinese medicine preparation is a soft capsule preparation, and the auxiliary material composition ratio is: 450 parts of seabuckthorn fruit oil, 173 parts of gelatin, 135 parts of purified water, 45 parts of glycerol, 25 parts of sorbitol, 2.4 parts of red iron oxide, and 0.3 parts of ethylparaben.

8. The method for preparing the Chinese medicine preparation according to claim 7, characterized in that: The preparation method comprises the following steps: Step (1): Weigh seabuckthorn fruit oil, stir at 35-43 rpm, mix for 25-35 minutes, and set aside; Step (2): Weigh ethylparaben and red iron oxide, add purified water to mix, add to a colloid mill, grind for 15 to 25 minutes, and collect the mixed solution; Step (3): Take sorbitol, add purified water and stir evenly; Step (4): Mix the ethyl hydroxybenzoate and red iron oxide mixture of step (2), the sorbitol solution of step (3), and glycerin, stir at a stirring speed of 45 to 55 rpm for 15 to 25 minutes to mix them evenly, then take gelatin, control and maintain the temperature at 80±5°C to dissolve and mix them evenly, adjust the vacuum degree to -0.06 to -0.07MPa, evacuate for 20 to 40 minutes, observe that there are no bubbles in the glue solution, evacuate statically for 10 to 15 minutes, pressurize the glue solution, pass it through a 60-mesh sieve, heat it to 60±5°C for insulation, input the gelatin into a pilling machine, apply a film, fill it with the seabuckthorn fruit oil solution of step (1), press the soft capsule, shape and dry it, select the pills, and you are done.

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