Medicament for treating hyperprolactinemia and preparation method thereof

Abstract

The application discloses a medicine for treating hyperprolactinemia, and the medicine is prepared from Bupleurum chinense, raw malt, Codonopsis pilosula, Atractylodes macrocephala Koidz, Radix Paeoniae Alba, Angelica sinensis, Chuanxiong Rhizoma, Cyperus rotundus, Fructus Lycii, Poria cocos, Radix Hedysari and Radix Glycyrrhizae. The medicine has the functions of soothing liver and relieving depression, invigorating spleen and benefiting qi, nourishing blood and regulating menstruation, can be used for treating diseases such as oligomenorrhea, menstrual period lag, amenorrhea, galactorrhea and infertility, and is suitable for patients with liver depression and spleen deficiency type hyperprolactinemia.

Description

Technical Field

[0001] This invention relates to a drug for treating hyperprolactinemia and its preparation method, belonging to the technical field of pharmaceuticals. Background Technology

[0002] Hyperprolactinemia (HPRL) refers to an abnormally high serum prolactin (PRL) level, >1.14 nmol / L (25 μg / L), caused by various factors. It affects HPOA, leading to related diseases. The main clinical symptoms include oligomenorrhea, galactorrhea, amenorrhea, and infertility. This disease has a high incidence rate and easily leads to menstrual disorders, infertility, and miscarriage, placing a heavy burden on patients' physical and mental health. Therefore, research on the treatment of this disease is of great clinical practical value.

[0003] Bromocriptine is currently the first-line drug commonly used in Western medicine to treat HPRL. It belongs to the D agonist class and can inhibit the secretion of PRL, restore gonadal function, and improve women's menstruation and related clinical symptoms. However, symptoms are prone to relapse after discontinuation of the drug. It has side effects such as orthostatic hypotension, nausea, vomiting, diarrhea, and dizziness. As a result, some patients have poor treatment compliance and therefore discontinue treatment, which delays the condition and causes it to continue to worsen.

[0004] Traditional Chinese medicine does not have a specific disease name for HPRL, but based on its clinical symptoms, it can be categorized under TCM terms such as "scanty menstruation," "delayed menstruation," "amenorrhea," "infertility," and "galactorrhea." Classical medical texts record its clinical manifestations and causes. For example, Xue Lizhai stated, "Blood is the essence of water and grain… in women, it ascends to become breast milk and descends to become menstrual blood." The *Jingyue Quanshu* states, "Women's breast milk is transformed from the Qi and blood of the Chong and Ren meridians; therefore, it descends to become menstruation and ascends to become breast milk." The formula of this invention has the effects of soothing the liver and relieving depression, strengthening the spleen and replenishing Qi, nourishing blood and regulating menstruation. It can treat diseases such as scanty menstruation, delayed menstruation, amenorrhea, galactorrhea, and infertility, and is suitable for patients with hyperprolactinemia of the liver-stagnation and spleen-deficiency type. Summary of the Invention

[0005] The technical problem to be solved by this invention is to provide a drug for treating hyperprolactinemia and its preparation method. This invention has the effects of warming the meridians and dispelling cold, invigorating qi and nourishing blood, and resolving blood stasis and relieving pain. It is used to treat lower abdominal pain that is aggravated by pressure before or during menstruation, which is relieved by hot compresses. It can also treat delayed menstruation, scanty menstruation, blood clots, as well as symptoms such as pale complexion, cold limbs, aversion to cold, white tongue coating, and deep, tight pulse. It is suitable for women with dysmenorrhea due to cold stagnation and blood stasis.

[0006] To solve the above technical problems, the present invention adopts the following technical solution: A drug for treating hyperprolactinemia, the active ingredients of which, by weight, are: 60-180 parts of Bupleurum chinense, 400-800 parts of malt, 100-200 parts of Codonopsis pilosula, 60-180 parts of Atractylodes macrocephala, 100-200 parts of Paeonia lactiflora, 60-180 parts of Angelica sinensis, 60-180 parts of Ligusticum chuanxiong, 60-180 parts of Cyperus rotundus, 100-200 parts of Lycium barbarum, 100-200 parts of Poria cocos, 60-180 parts of Achyranthes bidentata, and 30-90 parts of Glycyrrhiza uralensis.

[0007] The aforementioned drug for treating hyperprolactinemia comprises the following active ingredients by weight: 90-150 parts of Bupleurum chinense, 500-700 parts of malt, 120-180 parts of Codonopsis pilosula, 90-150 parts of Atractylodes macrocephala, 120-180 parts of Paeonia lactiflora, 90-150 parts of Angelica sinensis, 90-150 parts of Ligusticum chuanxiong, 90-150 parts of Cyperus rotundus, 120-180 parts of Lycium barbarum, 120-180 parts of Poria cocos, 90-150 parts of Achyranthes bidentata, and 40-80 parts of Glycyrrhiza uralensis.

[0008] Specifically, the aforementioned drug for treating hyperprolactinemia contains the following active ingredients by weight: 120 parts of Bupleurum chinense, 600 parts of malt, 150 parts of Codonopsis pilosula, 120 parts of Atractylodes macrocephala, 150 parts of Paeonia lactiflora, 120 parts of Angelica sinensis, 120 parts of Ligusticum chuanxiong, 120 parts of Cyperus rotundus, 150 parts of Lycium barbarum, 150 parts of Poria cocos, 120 parts of Achyranthes bidentata, and 60 parts of Glycyrrhiza uralensis.

[0009] The aforementioned method for preparing drugs for treating hyperprolactinemia involves weighing all the medicinal materials in the formula according to the specified proportions and processing them according to conventional preparation methods to produce the corresponding drug preparation.

[0010] The aforementioned pharmaceutical preparations include decoctions, hard capsules, granules, tablets, pills, or decoctions.

[0011] The aforementioned decoction is prepared as follows: Weigh each medicinal material according to the prescription ratio, add 5 times the amount of water, soak for 20 minutes, boil and reflux to extract 3 times, 20-25 minutes each time, combine the 3 extracts, mix well, concentrate to 60% of the original medicinal liquid, filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, take 1 times the weight of refined sugar, slowly add it to the above extract, stir well, continue to simmer over low heat to reduce the extract, when a small amount can be drawn into a thread or dripped onto paper without leaving water marks, bottle and seal, sterilize, and the product is ready.

[0012] The aforementioned hard capsules are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, soak for 1 hour, boil and reflux twice for 0.5 hours each time, combine the two extracts, mix well, concentrate to 60% of the original medicinal liquid, filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, dry the extract at 85℃ to form a dry extract, pulverize it into a fine powder, add 10% of the prepared amount of pregelatinized starch and mix evenly, granulate with 90% ethanol, dry at 75℃, granulate, and fill into capsules to obtain the final product.

[0013] The aforementioned granules are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 8 times the amount of water, soak for 1 hour, then boil and reflux to extract 3 times, 0.5 hours each time. Combine the 3 extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, and concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃. After vacuum drying, pulverize into fine powder to obtain dry extract. Take 1 part of dry extract and 1 part of sucrose, and prepare granules using a wet method with 90% ethanol. After granulation, dry at 65-75℃, pass through a 20-mesh sieve once, and then separate the fine powder using an 80-mesh sieve to obtain the final product.

[0014] The aforementioned tablets are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 5 times the amount of water, soak for 1 hour, then boil and reflux to extract 3 times, 1 hour each time. Combine the 3 extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, dry under reduced pressure, pulverize into a fine powder, prepare a soft mass with 50% ethanol, granulate through a 20-mesh sieve, granulate, dry at 70℃, add 1% sodium carboxymethyl starch and 2% microcrystalline cellulose, mix well, compress into tablets, and coat to obtain the final product.

[0015] The aforementioned pills are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, soak for 1 hour, then boil and reflux to extract twice, 1 hour each time. Combine the two extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, and concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃. Dry the extract at 75-80℃ to obtain a dry extract, pulverize it into a fine powder, take 1 part of the extract powder and 2 parts of starch paste, knead them evenly, let stand for 20-30 minutes, roll into strips, and make into pills.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The drug for treating hyperprolactinemia described in this invention is prepared from Bupleurum chinense, malt, Codonopsis pilosula, Atractylodes macrocephala, Paeonia lactiflora, Angelica sinensis, Ligusticum chuanxiong, Cyperus rotundus, Lycium barbarum, Poria cocos, Achyranthes bidentata, and Glycyrrhiza uralensis. The properties and effects of each component are as follows: Bupleurum chinense is the dried root of Bupleurum chinense DC., a plant of the Apiaceae family; it is harvested in spring and autumn, the stems, leaves, and soil are removed, and then it is dried; it is pungent and bitter in taste, and slightly cold in nature; it enters the liver, gallbladder, and lung meridians; it has the effects of dispersing and reducing fever, soothing the liver and relieving depression, and raising yang qi; it is used for colds with fever, alternating chills and fever, chest and rib pain, irregular menstruation, uterine prolapse, and rectal prolapse. Malt is a processed product made from the germinated and dried mature fruit of Hordeum vulgare L., a plant of the Poaceae family. It is sweet in taste and neutral in nature; it enters the spleen and stomach meridians; it has the functions of promoting qi circulation and digestion, strengthening the spleen and stomach, and reducing lactation and bloating; it is used for indigestion, abdominal distension and pain, spleen deficiency with poor appetite, milk stasis, breast distension and pain, weaning in women, liver stagnation with hypochondriac pain, and liver and stomach qi pain; raw malt has the functions of strengthening the spleen and stomach, and soothing the liver and promoting qi circulation; it is used for spleen deficiency with poor appetite and milk stasis. Codonopsis pilosula (Franch.) Nannf., Codonopsis pilosula Nannf. var. modesta (Nannf.) L. Shen, or Codonopsis tangsh en Oliv. are all plants belonging to the Strigaceae family. They are harvested in autumn, washed, and sun-dried. They are sweet in taste and neutral in nature; they enter the spleen and lung meridians; they have the effects of strengthening the spleen and lungs, nourishing blood and promoting body fluids; they are used for spleen and lung qi deficiency, poor appetite and fatigue, cough and wheezing, qi and blood deficiency, sallow complexion, palpitations and shortness of breath, thirst due to fluid depletion, and internal heat and thirst. Atractylodes macrocephala is the dried rhizome of Atractylodes macrocephala Koidz., a plant in the Asteraceae family. It is harvested in winter when the lower leaves turn yellow and the upper leaves become brittle. After removing the mud and sand, it is dried by baking or sun-drying, and then the fibrous roots are removed. It tastes bitter and sweet, and is warm in nature. It enters the spleen and stomach meridians. It has the effects of tonifying the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. It is used for spleen deficiency with poor appetite, abdominal distension and diarrhea, phlegm retention with dizziness and palpitations, edema, spontaneous sweating, and threatened abortion. Paeonia lactiflora is the dried root of Paeonia lactiflora Pall., a plant in the Ranunculaceae family. It tastes bitter and sour, and is slightly cold in nature. It enters the liver and spleen meridians. It has the effects of nourishing blood and regulating menstruation, astringing yin and stopping sweating, softening the liver and relieving pain, and calming liver yang. It is used for blood deficiency with chlorosis, irregular menstruation, spontaneous sweating, night sweats, hypochondriac pain, abdominal pain, limb spasms, headache, and dizziness.Angelica sinensis is the dried root of Angelica sinensis (Oliv.) Diels, a plant in the Apiaceae family. It is harvested in late autumn, with the fibrous roots and soil removed. After the moisture has slightly evaporated, it is bundled into small bunches, placed on a rack, and slowly dried with smoke. It has a sweet and pungent taste and is warm in nature; it enters the liver, heart, and spleen meridians. It has the effects of nourishing blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting bowel movements. It is used for blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, traumatic injuries, carbuncles and sores, and constipation due to intestinal dryness. Wine-processed Angelica sinensis promotes blood circulation and regulates menstruation; it is used for amenorrhea and dysmenorrhea, rheumatic arthralgia, and traumatic injuries. Chuanxiong is the dried rhizome of Ligusticum chuanxiong Hort., a plant of the Apiaceae family. It is harvested in summer when the nodes on the stem are prominent and slightly purplish. After removing the mud and sand, it is dried in the sun and then the fibrous roots are removed. It has a pungent taste and warm properties. It enters the liver, gallbladder, and pericardium meridians. It has the effects of promoting blood circulation, regulating qi, dispelling wind, and relieving pain. It is used for chest pain, chest and rib pain, swelling and pain from falls, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to masses, headache, and rheumatic pain. Cyperus rotundus L., a plant of the Cyperaceae family, is a dried rhizome. It is harvested in autumn, the hairs are singed off, and it is then briefly boiled or steamed in boiling water before being dried in the sun, or singed and then dried directly in the sun. It has a pungent, slightly bitter, and slightly sweet taste, and is neutral in nature. It enters the liver, spleen, and triple burner meridians. It has the effects of soothing the liver and relieving depression, regulating qi and relieving chest tightness, regulating menstruation and relieving pain. It is used for liver qi stagnation, chest and rib pain, hernia pain, breast pain, spleen and stomach qi stagnation, epigastric fullness and distension, abdominal pain, irregular menstruation, amenorrhea and dysmenorrhea. Goji berries are the dried, ripe fruit of *Lycium barbarum* L., a plant in the Solanaceae family. They are harvested in summer and autumn when ripe, the stems are removed, and the fruit is dried in a cool, shady place until the skin wrinkles. Then, it is sun-dried until the outer skin is hard and the flesh is soft. In rainy weather, they can be dried over a low heat. They are sweet in taste and neutral in nature; they enter the liver and kidney meridians. They nourish the liver and kidneys, benefit essence and improve eyesight. They are used for deficiency of essence and blood, lower back and knee pain, dizziness and tinnitus, impotence and seminal emission, internal heat and thirst, blood deficiency and chlorosis, and blurred vision. Poria cocos is the dried sclerotium of the fungus *Poria cocos* (Schw.) Wolf, a fungus in the Polyporaceae family. It is sweet and bland in taste and neutral in nature; it enters the heart, lung, spleen, and kidney meridians. It has the functions of promoting diuresis and eliminating dampness, strengthening the spleen, and calming the mind. It is used for edema with scanty urine, phlegm retention and dizziness, spleen deficiency and poor appetite, loose stools and diarrhea, restlessness, palpitations and insomnia. Achyranthes bidentata Bl. (also known as Huai Niu Xi) is the dried root of the plant Achyranthes bidentata Bl. (family Amaranthaceae). It tastes bitter, sweet, and sour, and is neutral in nature. It enters the liver and kidney meridians. It has the effects of removing blood stasis and promoting menstruation, tonifying the liver and kidneys, strengthening tendons and bones, promoting urination and relieving strangury, and guiding blood downward. It is used for amenorrhea, dysmenorrhea, soreness of the waist and knees, weakness of tendons and bones, strangury, edema, headache, dizziness, toothache, canker sores, hematemesis, and epistaxis.Licorice is the dried root and rhizome of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., or Glycyrrhiza glabra L., belonging to the Fabaceae family. It is harvested in spring and autumn, the fibrous roots are removed, and it is sun-dried. It has a sweet taste and neutral properties; it enters the heart, lung, spleen, and stomach meridians. It has the effects of tonifying the spleen and replenishing qi, clearing heat and detoxifying, resolving phlegm and relieving cough, relieving spasms and pain, and harmonizing other herbs. It is used for spleen and stomach weakness, fatigue, palpitations, shortness of breath, cough with excessive phlegm, abdominal and limb spasms and pain, carbuncles and boils, and to alleviate the toxicity and harshness of other drugs.

[0017] Fang Jie Hyperprolactinemia and oligomenorrhea are often caused by emotional stress, overwork, internal injury, and inherent deficiency, leading to dysfunction of the internal organs, disharmony of Qi and blood, and imbalance of Yin and Yang. Combined with the dual pressures of family and work for modern women, firstly, stress leads to emotional imbalance and stagnation of liver Qi, as stated in *The Mystery of Pregnancy*: "Great anger and depression injure the liver..."; *The Book of Changes* says: "When women are ill, they are often more prone to illness than men... because of excessive depression...". When the liver fails to regulate Qi and excessively suppresses the spleen, the spleen's digestive function weakens, leading to deficiency of both Qi and blood and insufficient production of nutrients. This prevents the Chong and Ren meridians from nourishing the uterus on time, resulting in scanty menstruation, delayed menstruation, or even amenorrhea and infertility. Furthermore, the upward flow of liver Qi prevents Yin blood from descending to the Chong and Ren meridians, causing it to flow upward and spontaneously generate milk. Secondly, overwork damages the spleen qi. As the *Neijing* states, "Overwork depletes qi..."; the *Yunyu Xuanji* says, "Overwork and poor diet injure the spleen." Damage to the spleen qi in the middle jiao weakens its digestive capacity, leading to insufficient sources of qi, blood, essence, and body fluids. Consequently, the blood in the Chong meridian fails to flow to the uterus, resulting in scanty menstruation, delayed menstruation, and infertility. Therefore, liver stagnation and spleen deficiency can cause hyperprolactinemia, scanty menstruation, hypochondriac pain, depression or irritability, poor appetite, abdominal distension, fatigue, and galactorrhea, among other related clinical manifestations. In liver stagnation and spleen deficiency, the liver qi rebels and suppresses the spleen, leading to spleen deficiency and impaired digestion. This results in insufficient qi and blood production, causing blood deficiency and leading to scanty menstruation, delayed menstruation, amenorrhea, and infertility. When liver qi is disordered, galactorrhea occurs. The liver governs the blood; stagnation of liver qi and blood in the uterus can also cause scanty menstruation, delayed menstruation, amenorrhea, and infertility. Since liver stagnation and spleen deficiency are common syndromes causing hyperprolactinemia and oligomenorrhea, Ding's Liver-Regulating and Milk-Expelling Decoction, which has the functions of soothing the liver and relieving stagnation, strengthening the spleen and replenishing qi, nourishing blood and regulating menstruation, was established to treat hyperprolactinemia caused by liver stagnation and spleen deficiency.

[0018] Bupleurum chinense, which enters the liver and gallbladder meridians, can soothe the liver, relieve depression, dispel wind, and reduce fever. Raw barley malt, used in large quantities, is sweet and neutral in nature, and can soothe liver qi, relieve depression, reduce lactation and swelling, and strengthen the spleen and stomach. As Zhang Xichun of the Qing Dynasty said, "Barley malt can enter the spleen and stomach... it is an auxiliary product for the spleen and stomach... it can soothe the liver and effectively reduce lactation." Codonopsis pilosula, sweet and neutral in nature, enters the spleen and lung meridians, and can tonify the lungs, strengthen the spleen, replenish qi, and nourish blood. Atractylodes macrocephala, bitter, sweet, and warm in nature, mainly enters the spleen and stomach meridians, and has the functions of tonifying qi and spleen, and calming the fetus. Bupleurum chinense combined with raw barley malt soothes liver depression, reduces the liver's influence on the spleen, and restores the spleen's digestive function. Codonopsis pilosula and Atractylodes macrocephala strengthen the spleen and replenish qi, ensuring a source for the generation of qi and blood. Sufficient qi and blood nourish the uterus and increase menstrual flow. These four herbs, which soothe liver depression, strengthen the spleen, and nourish blood, are the principal herbs. White peony root nourishes blood and softens the liver, regulates menstruation and relieves pain, and calms the liver. Wang Haogu said that peony root can "regulate the middle qi, treat spleen deficiency and fullness in the middle, ... pain under the ribs, ... insufficient liver blood." Angelica sinensis enters the liver, spleen, and heart meridians, nourishes blood, promotes blood circulation, regulates menstruation and relieves pain, and is known as the "holy medicine of blood." Ligusticum chuanxiong is pungent and warm in nature, enters the liver, gallbladder, and pericardium meridians, and has the functions of nourishing blood, promoting blood circulation, regulating qi and relieving pain. White peony root, angelica sinensis and bupleurum make the liver wood flow smoothly and the liver qi does not rise upward to produce milk. Ligusticum chuanxiong and angelica sinensis nourish blood and promote blood circulation, so that the spleen earth has a source for production and does not stagnate. The three medicines together are the assistant medicines. Goji berries are sweet and neutral in nature, entering the liver and kidney meridians. They nourish kidney essence and replenish liver blood, assisting white peony root, angelica root, and chuanxiong rhizome in nourishing blood and softening the liver. Poria cocos is sweet, bland, and neutral in nature, strengthening the spleen and stomach, and assisting codonopsis root and atractylodes rhizome in strengthening the spleen. Cyperus rhizome has the function of relieving liver stagnation, regulating qi, relieving pain, and regulating menstruation. Its effect of regulating qi and harmonizing the middle jiao can assist the effects of bupleurum root and chuanxiong rhizome in relieving liver stagnation, regulating qi, and relieving pain. These three herbs are used as adjuvant herbs. Achyranthes bidentata is sweet, bitter, sour, and neutral in nature, entering the kidney and liver meridians. It invigorates blood circulation, regulates menstruation, tonifies the liver and kidneys, strengthens tendons and bones, and guides blood downward. Licorice root enters the spleen and stomach meridians, tonifying the middle jiao, replenishing qi, and strengthening the spleen. Combined with white peony root, it can alleviate liver urgency and harmonize the effects of other herbs. Achyranthes bidentata and licorice root are used as guiding herbs. This formula combines the functions of soothing the liver and relieving depression, strengthening the spleen and replenishing qi, nourishing blood and regulating menstruation. It can treat diseases such as scanty menstruation, delayed menstruation, amenorrhea, galactorrhea, and infertility. It is suitable for patients with hyperprolactinemia of the liver stagnation and spleen deficiency type. Detailed Implementation

[0019] The present invention will be further described below with reference to embodiments, but these embodiments are not intended to limit the scope of the invention.

[0020] Example 1.

[0021] Prescription: Bupleurum chinense 120g, raw malt 600g, Codonopsis pilosula 150g, Atractylodes macrocephala 120g, Paeonia lactiflora 150g, Angelica sinensis 120g, Ligusticum chuanxiong 120g, Cyperus rotundus 120g, Lycium barbarum 150g, Poria cocos 150g, Achyranthes bidentata 120g, and Glycyrrhiza uralensis 60g.

[0022] Formulation process: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, soak for 1 hour, then boil and reflux twice for 0.5 hours each time. Combine the two extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, and concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃. Dry the extract at 85℃ to obtain a dry extract, pulverize it into a fine powder, add 10% of the prepared amount of pregelatinized starch and mix well. Granulate with 90% ethanol, dry at 75℃, granulate, and fill into capsules to obtain the decoction.

[0023] Dosage and administration: Take 15-25g three times a day, in the morning, noon and evening. Start taking the medicine on the 3rd day after menstruation ends and continue until the next menstruation. One menstrual cycle is one course of treatment, and a total of 3 courses of treatment are required.

[0024] Example 2.

[0025] Prescription: Bupleurum chinense 60g, raw malt 400g, Codonopsis pilosula 200g, Atractylodes macrocephala 180g, Paeonia lactiflora 200g, Angelica sinensis 60g, Ligusticum chuanxiong 180g, Cyperus rotundus 180g, Lycium barbarum 100g, Poria cocos 200g, Achyranthes bidentata 60g, and Glycyrrhiza uralensis 30g.

[0026] Formulation process: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, soak for 1 hour, then boil and reflux twice for 0.5 hours each time. Combine the two extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, and concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃. Dry the extract at 85℃ to obtain a dry extract, pulverize it into a fine powder, add 10% of the prepared amount of pregelatinized starch and mix evenly. Granulate with 90% ethanol, dry at 75℃, granulate, and fill into capsules to obtain hard capsules.

[0027] Dosage and administration: Take 3-5g (1g / capsule) three times a day, in the morning, noon and evening. Start taking the medicine on the 3rd day after menstruation ends and continue until the next menstruation. One menstrual cycle is one course of treatment, and a total of 3 courses of treatment are required.

[0028] Example 3.

[0029] Prescription: Bupleurum chinense 180g, raw malt 800g, Codonopsis pilosula 100g, Atractylodes macrocephala 60g, Paeonia lactiflora 100g, Angelica sinensis 180g, Ligusticum chuanxiong 60g, Cyperus rotundus 60g, Lycium barbarum 200g, Poria cocos 100g, Achyranthes bidentata 180g, and Glycyrrhiza uralensis 90g.

[0030] Formulation process: Weigh each medicinal material according to the prescription ratio, add 8 times the amount of water, soak for 1 hour, then boil and reflux to extract 3 times, 0.5 hours each time. Combine the 3 extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, and concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃. After vacuum drying, pulverize into fine powder to obtain dry extract. Take 1 part of dry extract and 1 part of sucrose, and prepare granules using 90% ethanol wet method. After granulation, dry at 65-75℃, pass through a 20-mesh sieve once, and separate the fine powder using an 80-mesh sieve to obtain granules.

[0031] Dosage and administration: Take 10-20g three times a day, in the morning, noon and evening. Start taking the medicine on the 3rd day after menstruation ends and continue until the next menstruation. One menstrual cycle is one course of treatment, and a total of 3 courses of treatment are required.

[0032] Example 4.

[0033] Prescription: Bupleurum chinense 130g, raw malt 500g, Codonopsis pilosula 140g, Atractylodes macrocephala 120g, Paeonia lactiflora 180g, Angelica sinensis 110g, Ligusticum chuanxiong 70g, Cyperus rotundus 80g, Lycium barbarum 160g, Poria cocos 200g, Achyranthes bidentata 90g, and Glycyrrhiza uralensis 40g.

[0034] Formulation process: Weigh each medicinal material according to the prescription ratio, add 5 times the amount of water, soak for 1 hour, then boil and reflux to extract 3 times, 1 hour each time. Combine the 3 extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, and concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃. After vacuum drying, pulverize into a fine powder, prepare a soft mass with 50% ethanol, granulate through a 20-mesh sieve, granulate, dry at 70℃, add 1% sodium carboxymethyl starch and 2% microcrystalline cellulose, mix well, compress into tablets, and coat to obtain tablets.

[0035] Dosage and administration: Take 3-5 tablets (1g / tablet) three times a day, in the morning, noon and evening. Start taking the medicine on the 3rd day after menstruation ends and continue until the next menstruation. One menstrual cycle is one course of treatment, and a total of 3 courses of treatment are required.

[0036] Example 5.

[0037] Prescription: Bupleurum chinense 90g, raw malt 700g, Codonopsis pilosula 110g, Atractylodes macrocephala 80g, Paeonia lactiflora 180g, Angelica sinensis 150g, Ligusticum chuanxiong 120g, Cyperus rotundus 60g, Lycium barbarum 200g, Poria cocos 120g, Achyranthes bidentata 70g, and Glycyrrhiza uralensis 80g.

[0038] Formulation process: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, soak for 1 hour, then boil and reflux twice for 1 hour each time. Combine the two extracts, mix well, and concentrate to 60% of the original medicinal liquid. Filter while hot, and concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃. Dry the extract at 75-80℃ to obtain a dry extract, pulverize it into a fine powder, take 1 part of the extract powder and 2 parts of starch paste, knead them evenly, let it stand for 20-30 minutes, roll it into strips, and make pills to obtain the pills.

[0039] Dosage and administration: Take 20-30mL three times a day, in the morning, noon and evening. Start taking the medicine on the 3rd day after menstruation ends and continue until the next menstruation. One menstrual cycle is one course of treatment, and a total of 3 courses of treatment are required.

[0040] Example 6.

[0041] Prescription: Bupleurum chinense 120g, raw malt 600g, Codonopsis pilosula 150g, Atractylodes macrocephala 120g, Paeonia lactiflora 150g, Angelica sinensis 120g, Ligusticum chuanxiong 120g, Cyperus rotundus 120g, Lycium barbarum 150g, Poria cocos 150g, Achyranthes bidentata 120g, and Glycyrrhiza uralensis 60g.

[0042] Formulation process: Weigh each medicinal material according to the prescription ratio, add 5 times the amount of water, soak for 20 minutes, boil and reflux to extract 3 times, each time for 20-25 minutes, combine the 3 extracts, mix well, filter, cool and package to obtain the decoction.

[0043] Dosage and administration: Take 200mL three times a day, in the morning, noon and evening. Start taking the medicine on the 3rd day after menstruation ends and continue until the next menstruation. One menstrual cycle is one course of treatment, and a total of 3 courses of treatment are required.

[0044] This invention has undergone extensive pharmacological experimental studies, and the results of these studies are as follows: 1. Clinical research data and methods 1.1 Source of Cases Sixty patients who met the inclusion criteria for oligomenorrhea due to hyperprolactinemia and liver stagnation and spleen deficiency and who visited the Eighth Clinic of the Traditional Chinese Medicine Hall at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine between January 2018 and December 2019 were included.

[0045] 1.2 Diagnostic criteria 1.2.1 Western Medicine Diagnostic Criteria It was developed with reference to the "Standards for Diagnosis and Treatment of Endocrine and Metabolic Diseases", "Obstetrics and Gynecology", and "Clinical Application Guidelines of the American Endocrine Society".

[0046] (1) Laboratory tests: A single serum prolactin level above 1.14 nmol / L (25 ug / L) can diagnose HPRL (the specimen was collected and tested by the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, and according to the hospital's standards, a single PRL level > 496 uIU / ml can be used for diagnosis).

[0047] (2) Clinical manifestations: ① oligomenorrhea, ② galactorrhea, ③ oligomenorrhea, ④ amenorrhea, ⑤ infertility, ⑥ sexual dysfunction, ⑦ headache and visual impairment, etc.

[0048] 1.2.2 Traditional Chinese Medicine Diagnostic Criteria Formulated with reference to "Traditional Chinese Medicine Gynecology", "Guiding Principles for Clinical Research of New Traditional Chinese Medicines", and "Traditional Chinese Medicine Diagnostics": Diagnosis: Scanty menstruation refers to menstruation with a normal menstrual cycle, but significantly reduced menstrual flow than before, or menstruation lasting less than 2 days, or even just spotting, for 2 or more consecutive menstrual cycles.

[0049] Traditional Chinese Medicine Syndromes: Main symptoms: Menstrual flow is reduced by more than one-third compared to the patient's previous period, with distending pain in the hypochondrium, poor appetite and abdominal distension.

[0050] Secondary symptoms: depression or irritability, loose stools, fatigue, and galactorrhea.

[0051] Tongue and pulse: The tongue is pale red with a white or greasy coating, and the pulse is thready or wiry.

[0052] Note: The above primary symptoms are essential, and two secondary symptoms are sufficient for diagnosis.

[0053] 1.3 Case screening criteria 1.3.1 Inclusion criteria: (1) Female patients aged 18 to 42 years; (2) Meets the diagnostic criteria for hyperprolactinemia in Western medicine; (3) Those who meet the criteria of liver stagnation and spleen deficiency type of scanty menstruation according to traditional Chinese medicine diagnosis; (4) Women with normal menstrual cycles and periods; (5) Informed consent, voluntary participation, and follow-up.

[0054] 1.3.2 Exclusion criteria: (1) Pituitary tumors, endometrial tuberculosis, endometrial-uterine adhesions and other organic lesions (such as growth hormone tumors, germ cell tumors, etc.); (2) Exclude patients with other endocrine disorders such as hypothyroidism; (3) Those whose PRL levels rise due to the use of estrogen, contraceptives, metoclopramide, domperidone, etc.; (4) Patients with severe cardiovascular, renal, or hepatic dysfunction, or those suffering from mental illness; (5) Patients who have used prolactin-lowering drugs within the past 3 months; (6) Individuals with multiple drug allergies or an allergic constitution; (7) Breastfeeding period.

[0055] 1.3.3 Criteria for shedding and rejection: (1) Those who are pregnant during medication; (2) Those who experience adverse reactions during treatment; (3) Those who voluntarily request to withdraw; (4) Those whose incomplete data affected the efficacy assessment and data statistics; (5) Those who cannot adhere to regular medication and complete treatment.

[0056] 1.3.4 Quantitative Standards for Traditional Chinese Medicine Symptoms: Patients' TCM syndrome scores were assessed and recorded before treatment and after each course of treatment. Efficacy was evaluated by observing changes in the scores. A quantitative scoring standard for TCM syndromes was drafted based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," as shown in Table 1 below. Table 1. Quantitative Scoring Standards for Traditional Chinese Medicine Syndromes Note: Tongue and pulse are recorded, but not scored.

[0057] 1.4 Research Methods: 1.4.1 Grouping method: According to the order of consultation, 60 patients who met the inclusion criteria were randomly divided into a treatment group (Ding's Gynecology "Liver-Regulating and Breast-Suppressing Decoction", hereinafter referred to as Liver-Regulating and Breast-Suppressing Decoction) and a control group (Xiaoyao Pill), with 30 patients in each group.

[0058] 1.4.2 Treatment methods: Treatment group: Administered a Liver-Regulating and Lactation-Suppressing Decoction, consisting of the following ingredients (one dose): Bupleurum chinense 120g, Hordeum vulgare 600g, Codonopsis pilosula 150g, Atractylodes macrocephala 120g, Paeonia lactiflora 150g, Angelica sinensis 120g, Ligusticum chuanxiong 120g, Cyperus rotundus 120g, Lycium barbarum 150g, Poria cocos 150g, Achyranthes bidentata 120g, and Glycyrrhiza uralensis 60g. Preparation method: Soak the herbs in water for approximately 20 minutes. First, bring to a boil over high heat, then simmer over low heat for approximately 20-25 minutes. Filter the dregs to obtain the decoction. Add water to the remaining dregs (no soaking required) and repeat the above decoction process twice more. Combine all the decoctions from the three decoctions. One dose per day, 3 times a day, 200ml each time. Begin taking the medicine on the 3rd day after menstruation ends and continue until the next menstrual period. One menstrual cycle constitutes one course of treatment, for a total of 3 courses. Pay attention to rest and emotional regulation.

[0059] Control group: Patients took Xiaoyao Pills (produced by Zhongjing Wanxi Pharmaceutical Co., Ltd., drug approval number Z41021831), starting on the 3rd day after menstruation ended, 8 pills each time, 3 times a day, until the next menstruation. One menstrual cycle is one course of treatment, and a total of 3 courses of treatment are required. Pay attention to rest and emotional regulation.

[0060] 1.4.3 Basis for selecting the control group Xiaoyao Wan is a traditional Chinese medicine made from Xiaoyao San. This formula comes from the Song Dynasty's "Taiping Huimin Heji Jufang" and is a famous formula for nearly a thousand years. It has the effects of harmonizing the liver and spleen, soothing the liver and relieving depression, nourishing blood and strengthening the spleen. According to novelty searches, Xiaoyao San as the main formula has good clinical efficacy in treating hyperprolactinemia, so it was selected as the control group.

[0061] 1.5 Observation Methods: 1.5.1 Observe and record the improvement of scanty menstruation before treatment and after each course of treatment.

[0062] 1.5.2 Observe and record the changes in the scores of various clinical symptoms before treatment and after each course of treatment.

[0063] 1.5.3 Changes in six female hormones were observed and recorded before treatment and after the third course of treatment. Before treatment and after the third course of treatment, blood was drawn from the forearm vein between 9:00 and 11:00 AM on the 2nd to 5th day of the menstrual cycle after fasting and resting for 30 minutes. (The day before the blood draw, patients should avoid sexual intercourse, maintain a calm mood, and get enough sleep.) Six female hormones were measured: PRL, E2, FSH, LH, P, and T (all samples were collected and tested by the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine).

[0064] 1.5.4 Observe and record changes in the endometrium before treatment and after the third course of treatment. Endometrial thickness is measured by gynecological ultrasound 5-7 days before menstruation, before treatment, and after the third course of treatment.

[0065] 1.6 Observation of any adverse drug reactions during medication use: Observe patients for adverse reactions during medication. If skin itching, rash, vomiting, diarrhea, abdominal pain, etc. occur, instruct the patient to stop taking the medication and exclude them from this study.

[0066] 1.7 Clinical symptom assessment: 1.7.1 Months of Less Treatment Efficacy Assessment: Formulated with reference to the "Traditional Chinese Medicine Diagnosis and Treatment Protocol" and the "General Principles for Clinical Research of New Traditional Chinese Medicine Drugs": Cure: After treatment, menstrual flow returns to its previous level, and the score decreases by ≥95% or to 0 points; Effective: After treatment, menstrual flow increased compared to before, and the score decreased by ≥30%; Ineffective: No increase in menstrual flow after treatment, and a decrease in score of <30%.

[0067] 1.7.2 Evaluation of TCM syndrome differentiation and treatment efficacy: Formulated in accordance with the "Standards for Diagnosis and Efficacy Evaluation of Diseases and Syndromes in Traditional Chinese Medicine" and the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs": Recovery: Menstrual flow returns to normal, and the scores of other symptoms decrease by ≥95%.

[0068] Significant effect: Menstrual flow increased by 2 / 3 compared to before treatment, and the scores of other symptoms decreased by ≥70% but <95%.

[0069] Effective: Menstrual flow increased after treatment compared to before treatment, and the scores of other symptoms decreased by ≥30% but <70%.

[0070] Ineffective: No increase in menstrual flow after treatment, and a decrease in score of <30%.

[0071] 1.8 Statistical Analysis: SPSS 16.0 statistical analysis software was used to statistically process the clinical research results. When the data met the criteria of homogeneity of variance and normal distribution, the t-test (parametric test) was used; otherwise, the t⁶ test (non-parametric test) was used. A p-value < 0.05 was considered statistically significant; a p-value > 0.05 was considered not statistically significant.

[0072] 2. Research Results 2.1 Comparison of the two sets of basic cases The youngest patient in the treatment group was 20 years old, and the oldest was 42 years old; the youngest patient in the control group was 21 years old, and the oldest was 42 years old. The shortest course of disease in the treatment group was 3 months, and the longest was 60 months; the shortest course of disease in the control group was 3 months, and the longest was 72 months. There were no statistically significant differences in age and course of disease between the two groups (P > 0.05), and the age and course of disease were comparable between the groups. (See Table 2 for details) Table 2: General situation of the two groups ( ) 2.2 Months of Treatment for Reduced Menstrual Flow: Comparison of Efficacy Before and After Treatment There was no statistically significant difference in the pre-treatment oligomenorrhea scores between the two groups (P=0.482>0.05), indicating comparability. After the first, second, and third courses of treatment, the effective rates in the treatment group were 63.33%, 76.67%, and 86.67%, respectively; while the effective rates in the control group were 60%, 66.67%, and 76.67%, respectively. Within each group, the differences after treatment were statistically significant (P=0.000<0.01), indicating that both groups could improve oligomenorrhea. Between-group comparisons after the first, second, and third courses of treatment showed P values ​​of 0.658 and 0.658, respectively. ■ 0.336 ▲ 0.045 ★ After the first and second courses of treatment, there were no statistically significant differences between the two groups (P > 0.05), indicating that there was no significant difference in the efficacy of improving oligomenorrhea between the two groups after the first and second courses of treatment. However, after the third course of treatment, the difference between the two groups was statistically significant (P = 0.045 < 0.05). Based on the above results, the treatment group showed better efficacy in improving oligomenorrhea than the control group. (See Tables 3 and 4 for details) Table 3: Comparison of the effective rates of improvement in oligomenorrhea after treatment between the two groups Note: Overall effectiveness rate = (effective + cured) / number of cases.

[0073] Table 4: Comparison of oligomenorrhea scores before and after treatment in the two groups ( )(point) Note: P: Comparison before and after treatment within the group; P ◆ : Intergroup comparison before treatment; P ■ : Intergroup comparison after the first course of treatment; P ▲ Intergroup comparison after the second course of treatment; P ★ Comparison between groups after the third course of treatment.

[0074] 2.3 Comparison of the efficacy of treatment for other individual TCM symptoms between groups before and after treatment Statistical analysis showed that, compared with the scores of other individual TCM symptoms before treatment, P < 0.05. 1 All values ​​were >0.05, indicating no statistically significant difference and comparability; within both the treatment and control groups, the difference before and after treatment was negligible (P > 0.05). 2All values ​​were <0.05, indicating statistically significant differences, suggesting that both the treatment and control groups improved TCM symptoms. After treatment, the differences in hypochondriac pain, emotional depression / irritability, and galactorrhea between the groups were all <0.05, indicating statistically significant differences, suggesting that the treatment group was superior to the control group in improving these symptoms. There were no statistically significant differences between the groups in improving symptoms of poor appetite, abdominal distension, loose stools, and fatigue, indicating no significant difference in improvement between the two groups in these symptoms. (See Table 5 for details) Table 5: Comparison of scores of other individual TCM symptoms before and after treatment among groups ( )(point) 2.4 Comparison of therapeutic effects before and after TCM syndrome treatment Before treatment, there were no statistically significant differences in TCM syndromes between the two groups (P=0.113>0.05), indicating comparability. After the first, second, and third courses of treatment, the total effective rates in the treatment group were 66.67%, 83.33%, and 90%, respectively; while in the control group, the total effective rates were 56.67%, 66.67%, and 83.33%, respectively. Further comparisons within each group after treatment showed statistically significant differences (P=0.000<0.01), indicating that both groups improved the relevant TCM syndromes. Between-group comparisons after the first, second, and third courses of treatment showed P values ​​of 0.608 and 0.608, respectively. ■ 0.081 ▲ 0.032 ★ At the end of the first and second treatment courses, there were no statistically significant differences between the two groups (P > 0.05), indicating that there was no significant difference in the overall improvement of TCM syndromes between the two groups after the first and second treatment courses. However, at the end of the third treatment course, the difference between the groups was statistically significant (P = 0.032 < 0.05). Based on the above results, the treatment group showed better efficacy in improving TCM syndromes than the control group. (See Tables 6 and 7) Table 6: Comparison of TCM Syndrome Efficacy Between Groups Note: The overall effective rate is the sum of cured, significantly effective, and effective cases divided by the total number of cases.

[0075] Table 7: Comparison of TCM syndrome scores before and after treatment in the two groups ( )(point) Note: P: comparison before and after treatment within the group; P ◆ : Intergroup comparison before treatment; P ■ : Intergroup comparison after the first course of treatment; P ▲ Intergroup comparison after the second course of treatment; P ★ Comparison between groups after the third course of treatment.

[0076] 2.5 Comparison of 6 female hormones before and after treatment between groups Comparison of PRL, FSH, LH, E2, P, and T levels in two groups before treatment; P 1 All values ​​> 0.05, indicating no statistically significant difference and comparability; within the two PRL groups, the difference before and after treatment was statistically insignificant. ☉ =0.000, indicating a statistically significant difference, meaning that PRL levels were lowered in both groups. For comparisons of PRL levels between the groups after treatment, P < 0.000. ◆ =0.003 ◆ <0.01, indicating a statistically significant difference, suggesting that the treatment group had a significantly better effect on lowering PRL than the control group. Within-group comparison of E2 in the treatment group after treatment (P < 0.01). ☉ =0.000 < 0.05, indicating a statistically significant difference, suggesting that the treatment group improved E2 levels after treatment; the control group showed improvement in E2 after treatment, but the intra-group comparison showed no significant difference. ☉ =0.069>0.05, the difference was not statistically significant, and the P-value was not statistically significant after comparison between the groups after treatment. ◆ =0.038 ◆ <0.05, the difference is statistically significant, indicating that both groups can increase E2, but the treatment group is better than the control group. Comparisons of FSH, P, LH, and T between groups and within groups before and after treatment (P) 1 P ◆ P ☉ All values ​​were >0.05, indicating no statistically significant difference. This suggests that the treatment had little effect on FSH, P, LH, and T levels in both groups (see Table 8 for details).

[0077] Table 8: Comparison of PRL, FSH, LH, E2, P, and T levels before and after treatment in the two groups ( ) Note: P 1 : Intergroup comparison before treatment; P ☉ : Comparison within the group before and after treatment; P ◆ : Intergroup comparison after treatment.

[0078] 2.6 Comparison of endometrial thickness before and after treatment between groups The average endometrial thickness before treatment was 6.13±1.44 mm, and after treatment it was 8.72±1.52 mm. In the control group, the average endometrial thickness before treatment was 6.28±1.32 mm, and after treatment it was 7.81±1.63 mm. The difference between the groups before treatment was statistically significant (P < 0.05). ◆ =0.700>0.05, the difference was not statistically significant, and they were comparable; within the group, comparing before and after treatment, P ●=0.000 < 0.05, indicating a statistically significant difference, meaning that both treatments improved endometrial thickness. Combined with the post-treatment comparison between the groups, P < 0.05. ◆ =0.040 < 0.05, the difference is statistically significant, indicating that the treatment group improved endometrial thickness better than the control group. (See Table 9 for details) Table 9: Comparison of endometrial thickness before and after treatment in the two groups (mm) Note: P ◆ Between-group comparison; P ● Intragroup comparison 2.7 Statistical analysis of adverse reaction results between groups No adverse reactions were found during the entire treatment process of 60 patients in the treatment group and the control group.

[0079] 3. Analysis and evaluation of the therapeutic effects of the study results 3.1 Evaluation of clinical efficacy (1) Evaluation of the efficacy of Tiaogan Yiru Decoction in improving oligomenorrhea of ​​HPRL type with liver stagnation and spleen deficiency: According to Tables 3 and 4, after 3 courses of treatment, the total effective rate of oligomenorrhea treatment group was 86.67%, while that of Xiaoyao Pill group was 76.67%. The difference between the two groups was statistically significant (P=0.045<0.05). This indicates that Tiaogan Yiru Decoction is effective in improving oligomenorrhea of ​​HPRL type with liver stagnation and spleen deficiency and is superior to the control group. According to the formula, Bupleurum chinense and malt can soothe the liver and promote the smooth flow of Qi and blood, while malt can strengthen the spleen. Codonopsis pilosula, Atractylodes macrocephala, and Poria cocos invigorate Qi and strengthen the spleen, assisting malt in strengthening the spleen and ensuring a strong source of menstrual blood. Paeonia lactiflora and Angelica sinensis nourish and replenish blood, ensuring a source of menstrual blood. Ligusticum chuanxiong and Cyperus rotundus assist Bupleurum chinense and malt in soothing the liver, ensuring that Qi and blood are replenished without stagnation. Lycium barbarum nourishes the liver and kidneys, and since metal and water share the same origin, it can both soothe and nourish the liver, and nourish the innate kidneys and the acquired spleen, thus ensuring smooth liver Qi and a strong spleen. Achyranthes bidentata nourishes the liver and kidneys and guides the medicine downward. Glycyrrhiza uralensis harmonizes all the medicines. The whole formula works together to ensure smooth liver Qi, strengthen the spleen, ensure a source of Qi and blood, and replenish the blood in the Chong and Ren meridians, which then flow down to the uterus, increasing menstrual blood. Furthermore, based on modern pharmacological research, malt inhibits PRL secretion, thereby weakening the inhibition on the hypothalamus, restoring the regulatory function of the hypothalamus-pituitary-ovarian axis, and promoting estrogen secretion by the ovaries. Additionally, peony root can stimulate the secretion of estrogen synthetin, promoting estrogen secretion; cyperus rhizome has estrogen-like effects, and estrogen can promote the proliferation of endometrial glands and stroma; angelica root, bupleurum root, and achyranthes root can excite the uterus, while chuanxiong rhizome and angelica root promote the production of red blood cells and hemoglobin; the angelica polysaccharide component of angelica root, combined with the tetramethylpyrazine component of chuanxiong rhizome, has a promoting effect on angiogenesis. Combining the above pharmacological research data and considering the synergistic effects of the drugs, increased menstrual flow may be related to the efficacy of this formula in improving ovarian function, uterine blood supply, local microcirculation, and endometrial thickness.

[0080] (2) Evaluation of the efficacy of Tiaogan Yiru Decoction in improving the TCM symptoms of HPRL with liver stagnation and spleen deficiency: The results in Tables 5 to 7 show that Tiaogan Yiru Decoction has a significant overall effect on improving the TCM symptoms of HPRL with liver stagnation and spleen deficiency, and is superior to Xiaoyao Pill. This is because the ingredients of Tiaogan Yiru Decoction, such as Bupleurum chinense, malt, Ligusticum chuanxiong, and Cyperus rotundus, can promote liver function, regulate emotions, and relieve pain; malt, Codonopsis pilosula, Atractylodes macrocephala, and Poria cocos benefit the spleen in the middle jiao; and Paeonia lactiflora and Angelica sinensis... This formula nourishes the blood, soothes the liver, and harmonizes the middle jiao, strengthening the spleen and softening the liver. Goji berries tonify the acquired kidneys, nourishing the liver and spleen, and assisting white peony root and angelica root in nourishing the blood and softening the liver. Achyranthes bidentata tonifies the liver and kidneys and guides the medicine downwards. Licorice root harmonizes the other herbs. The entire formula works synergistically to soothe the liver, relieve depression, strengthen the spleen, replenish qi, nourish the blood, and regulate menstruation. Therefore, it can improve symptoms related to HPRL (hepatitis B relapse) with liver stagnation and spleen deficiency, such as hypochondriac pain, depression or irritability, poor appetite, abdominal distension, fatigue, loose stools, and galactorrhea. Based on the above pharmacological research data, the improvement of symptoms such as hypochondriac pain, depression or irritability, poor appetite, abdominal distension, fatigue, loose stools, and galactorrhea may be related to the formula's effects of inhibiting PRL secretion, regulating the gonadal axis, improving microcirculation, and providing analgesia, sedation, and antispasmodic effects.

[0081] 3.2 Discussion of Laboratory Indicators 3.2.1 Discussion on the Influence of Six Female Hormones The results in Table 8 show that the Tiaogan Yiru Decoction significantly reduced PRL levels and increased E2 levels in patients with hypomenorrhea due to liver stagnation and spleen deficiency (HPRL), superior to the Xiaoyao Pill group. This is because increased PRL secretion by pituitary PRL cells stimulates the hypothalamus to secrete more D2 through short-feedback stimulation, thereby inhibiting PRL secretion. Excessive endogenous D2 inhibits hypothalamic GnRH secretion and can activate α-endorphin neuron activity, reducing GnRH synthesis. This weakens the pulsatile secretion of GnRH, leading to decreased pituitary GnRH, affecting ovarian function and estrogen secretion. It weakens or eliminates the positive feedback effect of estrogen, and can also directly inhibit ovarian function, reducing estrogen production and affecting endometrial hyperplasia, thus causing hypomenorrhea. When PRL levels return to normal after treatment, the inhibition of the hypothalamus-pituitary-ovarian axis and the inhibition of ovarian steroid hormone metabolism are relieved, allowing the ovaries to synthesize and secrete estrogen normally, resulting in increased estrogen levels. This may be related to the combined effects of the formula, such as the inhibition of PRL secretion by raw malt, the stimulation of estrogen synthesis by peony root, the promotion of estradiol secretion, and the estrogen-like effects of cyperus rhizome.

[0082] 3.2.2 Discussion on the Influence of Endometrial Thickness The results in Table 9 show that the Liver-Regulating and Lactation-Suppressing Decoction (Tiaogan Yiru Tang) is superior to Xiaoyao Wan in improving endometrial thickness in patients with hypomenorrhea due to liver stagnation and spleen deficiency in HPRL. The effectiveness of Tiaogan Yiru Tang in improving endometrial thickness in HPRL patients with liver stagnation and spleen deficiency may be related to the above research indicating that this formula can lower serum prolactin levels, restore ovarian function, and promote estrogen synthesis and secretion. This is because one of the important physiological functions of estrogen is to promote the proliferation of endometrial stroma and glands. Many herbs in the formula, such as Angelica sinensis and Ligusticum chuanxiong, have been shown in pharmacological studies to improve microcirculation, promote hemoglobin and erythrocyte production, and promote angiogenesis, thereby improving local blood supply and circulation in the endometrium, providing nutrition to the endometrium, promoting endometrial proliferation, and improving menstrual flow.

[0083] The above studies indicate that Tiaogan Yilu Decoction can improve oligomenorrhea and TCM symptoms in HPRL type with liver stagnation and spleen deficiency. This may be related to the fact that the formula's functions of relieving liver stagnation, strengthening the spleen and replenishing qi, nourishing blood and regulating menstruation can reduce PRL levels, increase E2 levels, increase endometrial thickness, improve blood circulation, stimulate the uterus, and have analgesic and sedative effects.

[0084] 4. Conclusion (1) Ding's Gynecology "Liver-Regulating and Lactation-Suppressing Decoction" has a significant effect on treating oligomenorrhea of ​​liver stagnation and spleen deficiency type with hyperprolactinemia and improving TCM symptoms, and is superior to Xiaoyao Pill.

[0085] (2) Ding's Gynecology "Liver-Regulating and Lactation-Suppressing Decoction" significantly reduced PRL in patients with hyperprolactinemia and liver stagnation and spleen deficiency type of oligomenorrhea, and could increase patients' E2 level, which was superior to Xiaoyao Pill; it had no significant effect on FSH, LH, P and T values; (3) Ding's Gynecology "Liver-Regulating and Lactation-Suppressing Decoction" can improve endometrial thickness and is superior to Xiaoyao Pill.

[0086] 5. Typical Cases 5.1. Typical Case 1 Patient Guan, female, 30 years old, presented to our outpatient department on August 9, 2025, with a history of amenorrhea for 4+ months. Present medical history: Last menstrual period was initiated after taking Climara, lasting 8 days without stopping. Currently experiencing frequent dreams, restless sleep, and easy awakening. No past medical history. No history of allergies.

[0087] According to the four diagnostic methods of Traditional Chinese Medicine: normal complexion, normal appearance, normal voice, normal breathing, pale red tongue, normal tongue body, slightly red edges and tip of the tongue, and thready and wiry pulse.

[0088] Clinical diagnosis: Traditional Chinese Medicine Diagnosis: 1. Delayed menstruation due to liver stagnation and spleen deficiency: Western medicine diagnosis: 1. Hyperprolactinemia.

[0089] Treatment prescription (one dose): Bupleurum chinense 12g, raw malt 60g, Codonopsis pilosula 15g, Atractylodes macrocephala 12g, Paeonia lactiflora 15g, Angelica sinensis 12g, Ligusticum chuanxiong 12g, Cyperus rotundus 12g, Lycium barbarum 15g, Poria cocos 15g, Achyranthes bidentata 12g and Glycyrrhiza uralensis 6g.

[0090] Take 7 doses of traditional Chinese medicine, one dose per day (divided into three times), orally.

[0091] Seven days later, she returned for a follow-up visit. Five days after taking the medication, her period started. At the follow-up visit, it was the second day of her period, with moderate flow, bright red color, no dysmenorrhea, and her frequent dreams and easy waking were better than before. Her menstrual condition had improved.

[0092] 5.2. Typical Case 2 Patient An, female, 26 years old, presented to our outpatient department on October 25, 2025, with a history of miscarriage after 1 year and 6+ months of trying to conceive. Present medical history: positive antisperm antibody (120µ / ml), 33-day menstrual cycle, dysmenorrhea, fatigue, staying up late (2-3 AM), normal appetite and sleep, irritability, and normal bowel movements. No epidemiological history. No history of allergies.

[0093] Sex hormones: LH: 10.5 µV / ml; FSH: 6.22 µIV / ml; PRL: 889.00 µIV / ml; According to the four diagnostic methods of Traditional Chinese Medicine: normal complexion, normal appearance, normal voice, normal breathing, pale tongue, swollen tongue body, thin white coating, and wiry pulse.

[0094] Clinical diagnosis: Traditional Chinese Medicine Diagnosis: 1. Delayed menstruation due to liver stagnation and spleen deficiency: Western medicine diagnosis: 1. Hyperprolactinemia; recurrent miscarriage.

[0095] Treatment prescription (one dose): Bupleurum chinense 12g, raw malt 60g, Codonopsis pilosula 15g, Atractylodes macrocephala 12g, Paeonia lactiflora 15g, Angelica sinensis 12g, Ligusticum chuanxiong 12g, Cyperus rotundus 12g, Lycium barbarum 15g, Poria cocos 15g, Achyranthes bidentata 12g and Glycyrrhiza uralensis 6g.

[0096] Take 7 doses of traditional Chinese medicine, one dose per day (divided into three times), orally.

[0097] Two weeks later, she returned for a follow-up visit. (Currently, her sleep has improved, her period has started after taking the medication, and the amount and color are both normal. Her menstrual cramps have significantly improved compared to before, and her irritability and fatigue have also improved.) Her menstrual condition has improved.

[0098] 5.3. Typical Case 3 Patient Qin, female, 39 years old, visited our outpatient department on April 18, 2026, due to "delayed menstruation". Present illness: last menstrual period was light, lasted 3 days, with blood clots, currently staying up late (11-12 pm), experiencing frequent dreams, good appetite and sleep, and normal bowel movements. No past medical history.

[0099] Sex hormones: LH: 10.23 µIV / ml; FSH: 27.95 µIV / ml; PRL: 725µIV / ml; AMH: 0.1 ng / ml.

[0100] According to the four diagnostic methods of Traditional Chinese Medicine: normal complexion, normal appearance, normal voice, normal breathing, pale and dark tongue, normal tongue body, thin and greasy tongue coating, and wiry and thready pulse.

[0101] Clinical diagnosis: Traditional Chinese Medicine Diagnosis: 1. Liver Qi Stagnation and Spleen Deficiency Syndrome: Western medicine diagnosis: 1. Hyperprolactinemia.

[0102] Treatment prescription (one dose): Bupleurum chinense 12g, raw malt 60g, Codonopsis pilosula 15g, Atractylodes macrocephala 12g, Paeonia lactiflora 15g, Angelica sinensis 12g, Ligusticum chuanxiong 12g, Cyperus rotundus 12g, Lycium barbarum 15g, Poria cocos 15g, Achyranthes bidentata 12g and Glycyrrhiza uralensis 6g.

[0103] Take 7 doses of traditional Chinese medicine, one dose per day (divided into three times), orally.

[0104] Two weeks later, she returned for a follow-up visit, reporting that her menstruation had resumed after finishing the medication, with a slightly heavier flow than before, lasting for 5 days, containing a few blood clots, no dysmenorrhea, and her excessive dreaming had lessened. Her menstrual condition had improved.

Claims

1. A drug for treating hyperprolactinemia, characterized in that: Its medicinal active ingredients, calculated by weight, are made from 60-180 parts of Bupleurum chinense, 400-800 parts of malt, 100-200 parts of Codonopsis pilosula, 60-180 parts of Atractylodes macrocephala, 100-200 parts of Paeonia lactiflora, 60-180 parts of Angelica sinensis, 60-180 parts of Ligusticum chuanxiong, 60-180 parts of Cyperus rotundus, 100-200 parts of Lycium barbarum, 100-200 parts of Poria cocos, 60-180 parts of Achyranthes bidentata, and 30-90 parts of Glycyrrhiza uralensis.

2. The medicament for treating hyperprolactinemia as described in claim 1, characterized in that: Its medicinal active ingredients, calculated by weight, are made from 90-150 parts of Bupleurum chinense, 500-700 parts of malt, 120-180 parts of Codonopsis pilosula, 90-150 parts of Atractylodes macrocephala, 120-180 parts of Paeonia lactiflora, 90-150 parts of Angelica sinensis, 90-150 parts of Ligusticum chuanxiong, 90-150 parts of Cyperus rotundus, 120-180 parts of Lycium barbarum, 120-180 parts of Poria cocos, 90-150 parts of Achyranthes bidentata, and 40-80 parts of Glycyrrhiza uralensis.

3. The medicament for treating hyperprolactinemia as described in claim 1 or 2, characterized in that: Its medicinal active ingredients, calculated by weight, are made from 120 parts of Bupleurum chinense, 600 parts of raw malt, 150 parts of Codonopsis pilosula, 120 parts of Atractylodes macrocephala, 150 parts of Paeonia lactiflora, 120 parts of Angelica sinensis, 120 parts of Ligusticum chuanxiong, 120 parts of Cyperus rotundus, 150 parts of Lycium barbarum, 150 parts of Poria cocos, 120 parts of Achyranthes bidentata, and 60 parts of Glycyrrhiza uralensis.

4. A method for preparing the medicament for treating hyperprolactinemia as described in any one of claims 1-3, characterized in that: Weigh all the medicinal materials in the formula according to the proportions, and process them according to conventional preparation methods to make the corresponding pharmaceutical preparations.

5. The method for preparing the medicament for treating hyperprolactinemia as described in claim 4, characterized in that: The pharmaceutical preparations include decoctions, hard capsules, granules, tablets, pills, or decoctions.

6. The method for preparing the medicament for treating hyperprolactinemia as described in claim 5, characterized in that: The decoction is prepared as follows: Weigh each medicinal material according to the prescription ratio, add 5 times the amount of water, soak for 20 minutes, boil and reflux to extract 3 times, 20-25 minutes each time, combine the 3 extracts, mix well, concentrate to 60% of the original medicinal liquid, filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, take 1 times the weight of refined sugar, slowly add it to the above extract, stir well, continue to simmer over low heat to reduce the extract, when a small amount can be drawn into a thread or dripped onto paper without leaving water marks, bottle and seal, sterilize, and the product is ready.

7. The method for preparing the medicament for treating hyperprolactinemia as described in claim 5, characterized in that: The hard capsules are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, soak for 1 hour, boil and reflux twice for 0.5 hours each time, combine the two extracts, mix well, concentrate to 60% of the original medicinal liquid, filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, dry the extract at 85℃ to a dry extract, pulverize into a fine powder, add 10% of the prepared amount of pregelatinized starch and mix evenly, granulate with 90% ethanol, dry at 75℃, granulate, and fill into capsules to obtain the final product.

8. The method for preparing the medicament for treating hyperprolactinemia as described in claim 5, characterized in that: The granules are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 8 times the amount of water, soak for 1 hour, boil and reflux to extract 3 times, 0.5 hours each time, combine the 3 extracts, mix well, concentrate to 60% of the original medicinal liquid, filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, dry under reduced pressure, and pulverize into fine powder to obtain dry extract. Take 1 part of dry extract and 1 part of sucrose, prepare granules using 90% ethanol wet method, dry the granules at 65-75℃, pass through a 20-mesh sieve once, and separate the fine powder with an 80-mesh sieve to obtain the final product.

9. The method for preparing the medicament for treating hyperprolactinemia as described in claim 5, characterized in that: The tablets are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 5 times the amount of water, soak for 1 hour, boil and reflux to extract 3 times, 1 hour each time, combine the 3 extracts, mix well, concentrate to 60% of the original medicinal liquid, filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, dry under reduced pressure, pulverize into fine powder, make soft material with 50% ethanol, granulate through a 20-mesh sieve, granulate, dry at 70℃, add 1% sodium carboxymethyl starch and 2% microcrystalline cellulose, mix well, compress into tablets, and coat to obtain the final product.

10. The method for preparing the medicament for treating hyperprolactinemia as described in claim 5, characterized in that: The pills are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, soak for 1 hour, boil and reflux twice for 1 hour each time, combine the two extracts, mix well, concentrate to 60% of the original medicinal liquid, filter while hot, concentrate the filtrate to an extract with a relative density of 1.21-1.25 at 50-60℃, dry the extract at 75-80℃ to a dry extract, pulverize it into a fine powder, take 1 part of the extract powder and 2 parts of starch paste, knead evenly, let stand for 20-30 minutes, roll into strips, and make into pills to obtain the product.

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