Traditional Chinese medicine composition for treating blood stasis collateral obstruction type femoral head necrosis as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to a traditional Chinese medicine composition for treating blood stasis collateral obstruction type femoral head necrosis as well as a preparation method and application of the traditional Chinese medicine composition, which can effectively solve the medication problem of blood stasis collateral obstruction type ulcer type femoral head necrosis. The traditional Chinese medicine is prepared from, by weight, 10-20 g of angelica sinensis, 7-13 g of peach kernels, 7-13 g of ligusticum wallichii, 7-13 g of radix paeoniae rubra, 4-8 g of honey-fried licorice roots, 8-16 g of prepared rehmannia roots, 13-27 g of curcuma zedoary, 13-27 g of rhizoma sparganii, 5-11 g of ground beetles, 10-20 g of radix achyranthis bidentatae, 8-16 g of suberect spatholobus stems, 10-20 g of astragalus membranaceus and 4-8 g of licorice roots. The traditional Chinese medicine composition has a remarkable effect on treating the blood stasis collateral obstruction type femoral head necrosis, has a good long-term curative effect, is not easy to relapse, is easily accepted by patients, and is an innovation on medicines for treating the blood stasis collateral obstruction type femoral head necrosis.

Description

1. Technical Field

[0001] The invention relates to the field of medicine, in particular to a traditional Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis, and a preparation method and application thereof. 2. Background Technology

[0002] Femoral head necrosis is a common clinical orthopedic disease. It is difficult to treat and disabling. It is a pathological evolution process. It often starts in the weight-bearing area of ​​the femoral head. Under the action of force, the necrotic bone structure is damaged, resulting in repeated imperfect repair, resulting in changes in the femoral head structure or collapse and deformation. Femoral head necrosis will cause severe pain and joint mobility dysfunction in patients. Common clinical symptoms include pain, which is mostly located in the hip joint and proximal thigh, resulting in limited hip movement, especially limited rotational movement, or painful and shortened claudication, which seriously endangers the patient's quality of life and even life safety. The current incidence of ONFH is increasing year by year, seriously affecting the quality of life of patients and bringing a considerable economic burden to their families. Studies have shown that patients with ONFH who have not been effectively treated will experience femoral head collapse within 1 to 5 years of onset, which directly affects the function of the hip joint, and ultimately can only be improved through joint replacement surgery. At present, hip preservation treatment is mainly adopted for early and middle-stage ONFH at home and abroad to stabilize the morphology of the femoral head and delay collapse, thereby delaying the time for hip replacement surgery.

[0003] Femoral head necrosis belongs to the category of "bone atrophy" and "bone failure" in traditional Chinese medicine. "The kidney governs bones, the liver governs tendons, and bones produce marrow." Traditional Chinese medicine believes that the main causes of this disease are liver and kidney deficiency, insufficient qi and blood, lack of nourishment to tendons and bones, joint strain, cold and dampness, and blood stasis. The root cause of this disease is liver and kidney deficiency. This disease is prone to recurrence. For this reason, traditional Chinese medicine treatment advocates that this disease is mostly due to deficiency in the root and excess in the superficial, with liver and kidney deficiency and spleen and stomach dysfunction. The kidney-tonifying and bone-strengthening method has the effect of nourishing the liver and kidney and strengthening tendons and bones, which can effectively improve the symptoms of such patients. Chinese herbal decoctions can improve the Harris and JOA scores of patients with femoral head ischemic necrosis, relieve their pain, and are safer. Traditional Chinese medicine conservative treatment has unique therapeutic advantages in preventing and treating femoral head necrosis, and has an improving effect on blood rheology and blood lipids. We believe that the pathogenesis of femoral head necrosis is not single, and it is related to multiple organs such as liver, kidney, spleen, bladder, etc., but it is most closely related to liver and kidney. Kidney governs bones, and bone diseases are treated from the perspective of kidney. It is in line with the theory of traditional Chinese medicine to take kidney tonification as the fundamental treatment goal to strengthen tendons and bones. However, patients with blood stasis and collateral obstruction are also part of the treatment in clinical work, but there are few existing studies. In view of this, the inventors proposed blood stasis and collateral obstruction type femoral head necrosis, and invented a Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis, as well as its preparation method and application. III. Summary of the invention

[0004] In view of the above situation, in order to solve the defects of the prior art, the purpose of the present invention is to provide a traditional Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis and its preparation method and application, which can effectively solve the medication problem of blood stasis and collateral obstruction type ulcerative femoral head necrosis.

[0005] The inventor found that the TCM syndrome is manifested as dark complexion, lip color, skin color or pigmentation due to blood stasis, easy bruises, relatively rough skin, obvious dandruff, easy bruises, irritable temperament and forgetfulness. Women are mostly dark eye sockets, dark nose, easy hair loss, dry skin or nails, dysmenorrhea, amenorrhea, or purple-black menstruation with clots, metrorrhagia. The pain is severe, refusing to press, and the location is fixed; the lips are dull or purple, the tongue is dark with petechiae or flaky ecchymosis, and sublingual varicose veins. The pulse is thin and astringent.

[0006] Based on this, the technical solution solved by the present invention is a traditional Chinese medicine composition for treating femoral head necrosis of blood stasis and obstruction type, which is made of the following raw materials by weight: 10-20g of Angelica sinensis, 7-13g of peach kernel, 7-13g of Chuanxiong, 7-13g of red peony root, 4-8g of roasted liquorice, 8-16g of Rehmannia glutinosa, 13-27g of Curcuma zedoaria, 13-27g of Trillium, 5-11g of Eupolyphaga sinensis, 10-20g of Achyranthes bidentata, 8-16g of Millettia reticulata, 10-20g of Astragalus and 4-8g of Licorice.

[0007] Preferably, the Chinese medicine composition is made of the following raw materials by weight: 15g of Angelica sinensis, 10g of peach kernel, 10g of Chuanxiong, 10g of red peony root, 6g of roasted liquorice, 12g of Rehmannia glutinosa, 20g of Curcuma zedoaria, 20g of Trigonosciadium japonicum, 8g of Eupolyphaga sinensis, 15g of Achyranthes bidentata, 12g of Millettia spatholobi, 15g of Astragalus and 6g of Licorice.

[0008] The preparation method of the Chinese medicine composition can be made into different dosage forms such as decoction, pills, tablets, granules, pastes, etc.

[0009] Furthermore, the preparation method of the water decoction is as follows: add 400-600 ml of water to the above raw material drugs, soak for 15-25 minutes at 18-25°C, then boil over high heat, then turn to low heat, boil for 20-30 minutes, filter, obtain filtrate, and set aside; add 300-400 ml of water to the filter residue, boil over high heat, then turn to low heat, boil for 10-15 minutes, filter, discard the filter residue, obtain filtrate, combine the two filtrates, and concentrate to 1 / 2-1 / 3 of the amount of water added twice.

[0010] The invention has abundant raw materials, simple preparation method, effective combination of prescription drugs, mutual support, and scientific preparation, and has the effect of promoting blood circulation and removing blood stasis. It has significant effect in treating femoral head necrosis of blood stasis and collateral obstruction type, and has good long-term efficacy, is not prone to recurrence, and is easily accepted by patients. It is an innovation in drugs for treating femoral head necrosis of blood stasis and collateral obstruction type. IV. Description of the drawings

[0011] Figure 1 This is the modeling result of the steroid-induced femoral head necrosis model in the animal experiment of the present invention. V. Specific implementation methods

[0012] The specific implementation modes of the present invention are further described in detail below in conjunction with the embodiments.

[0013] Example 1

[0014] When the present invention is implemented, the Chinese medicine soup can be prepared from the following raw materials by weight: 10g of angelica sinensis, 7g of peach kernel, 7g of chuanxiong, 7g of red peony root, 4g of roasted liquorice, 8g of prepared rehmannia root, 13g of curcuma, 13g of triangularis, 5g of earthworm, 10g of achyranthes bidentata, 8g of millettia spatholobi, 10g of astragalus and 4g of liquorice.

[0015] The preparation method is as follows: add 400 ml of water to the above raw material drugs, soak for 15 minutes at 18°C, then boil over high heat, then turn to low heat, boil for 20 minutes, filter, obtain filtrate, and set aside; add 300 ml of water to the residue, boil over high heat, then turn to low heat, boil for 10 minutes, filter, discard the residue, obtain filtrate, combine the two filtrates, and concentrate to 1 / 2 of the amount of water added twice.

[0016] Example 2

[0017] In the specific implementation of the present invention, the Chinese medicine soup can also be made from the following raw materials by weight: 15g of angelica, 10g of peach kernel, 10g of chuanxiong, 10g of red peony root, 6g of roasted licorice, 12g of prepared rehmannia, 20g of curcuma, 20g of triangularis, 8g of earthworm, 15g of achyranthes, 12g of millettia reticulata, 15g of astragalus and 6g of licorice.

[0018] The preparation method is as follows: add 500 ml of water to the above raw material drugs, soak for 20 minutes at 21°C, then boil over high heat, then turn to low heat, boil for 25 minutes, filter, obtain filtrate, and set aside; add 350 ml of water to the residue, boil over high heat, then turn to low heat, boil for 12 minutes, filter, discard the residue, obtain filtrate, combine the two filtrates, and concentrate to 1 / 3 of the amount of water added twice.

[0019] Example 3

[0020] In the specific implementation of the present invention, the Chinese medicine soup can also be made from the following raw materials by weight: 20g of angelica, 13g of peach kernel, 13g of chuanxiong, 13g of red peony root, 8g of roasted liquorice, 16g of prepared rehmannia, 27g of curcuma, 27g of triangularis, 11g of earthworm, 20g of achyranthes, 16g of millettia reticulata, 20g of astragalus and 8g of liquorice.

[0021] The preparation method is as follows: add 600 ml of water to the above raw material drugs, soak for 25 minutes at 25°C, then boil over high heat, then turn to low heat, boil for 30 minutes, filter, obtain filtrate, and set aside; add 400 ml of water to the residue, boil over high heat, then turn to low heat, boil for 15 minutes, filter, discard the residue, obtain filtrate, combine the two filtrates, and concentrate to 1 / 2 of the amount of water added twice.

[0022] In the prescription of the present invention:

[0023] Angelica sinensis is sweet, spicy and warm in nature. It enters the spleen, liver and heart meridians. It nourishes blood, promotes blood circulation, removes blood stasis and relieves pain.

[0024] Peach kernel tastes bitter and sweet, and is neutral in nature. It enters the liver, heart, and large intestine meridians. It promotes blood circulation and removes blood stasis.

[0025] Chuanxiong is pungent and warm in nature. It enters the liver, gallbladder and pericardium meridians. It promotes blood circulation, qi circulation, dispels wind and relieves pain.

[0026] Red peony root is bitter and cold in nature. It enters the liver meridian. It clears away heat, cools blood, disperses blood stasis and relieves pain.

[0027] Roasted Licorice root is sweet and neutral in nature. It enters the heart, lung, spleen and stomach meridians. It replenishes qi and restores pulse, nourishes spleen and stomach, and harmonizes the properties of the medicine.

[0028] Rehmannia root is sweet and slightly warm in nature. It enters the liver and kidney meridians. It nourishes blood and yin, replenishes essence and fills marrow.

[0029] Curcuma zedoaria is pungent and bitter in taste and warm in nature. It enters the liver, spleen and stomach meridians. It promotes qi and resolves blood, eliminates stagnation and relieves pain.

[0030] Trigonum multiflorum is bitter in taste and neutral in nature. It enters the liver and spleen meridians. It can promote blood circulation, relieve swelling and relieve pain.

[0031] The earthworm tastes salty and is cold in nature. It enters the liver meridian. It can break blood and remove blood stasis, and heal tendons and bones.

[0032] Achyranthes bidentata tastes sweet, slightly bitter, and is neutral in nature. It enters the liver and kidney meridians. It nourishes the liver and kidneys, strengthens the tendons and bones, removes blood stasis and relieves pain.

[0033] Millettia reticulata tastes bitter and sweet, and is warm in nature. It enters the liver and kidney meridians. It replenishes blood, promotes blood circulation, and relieves pain.

[0034] Astragalus is sweet and warm in nature. It enters the spleen and lung meridians. It replenishes qi, strengthens the exterior, promotes the production of body fluids and nourishes blood.

[0035] Licorice is sweet and neutral in nature. It enters the spleen, stomach, heart, and lung meridians. It nourishes the spleen and replenishes qi, relieves pain, and harmonizes various medicines.

[0036] The effective combination of the above drugs supports each other and is scientifically prepared to have the function of promoting blood circulation and removing blood stasis. In the prescription, Angelica sinensis is the main drug for nourishing blood and promoting blood circulation, removing blood stasis and relieving pain. The combination of peach kernel, Chuanxiong, and red peony root constitutes a classic combination of promoting blood circulation and removing blood stasis. Peach kernel promotes blood circulation and removes blood stasis, Chuanxiong promotes blood circulation and qi, and red peony root clears heat and cools blood, disperses blood stasis and relieves pain. The combination can effectively promote blood circulation and remove blood stasis, and relieve pain caused by blood stasis; Millettia reticulata, Curcuma zedoaria, Trillium, and Eupolyphaga sinensis promote blood circulation and remove blood stasis, and promote qi and relieve pain. The combination can enhance the effect of promoting blood circulation and removing blood stasis; they are all minister drugs to enhance the effect of promoting blood circulation and removing blood stasis. Rehmannia root nourishes yin and blood, Astragalus root replenishes qi and consolidates the exterior, Achyranthes bidentata nourishes the liver and kidney, strengthens tendons and bones, promotes blood circulation and removes blood stasis, and guides blood downward, and roasted licorice harmonizes the spleen and stomach, and they are all adjuvant drugs. Licorice harmonizes all drugs as the guiding drug. The compatibility of the entire prescription takes into account multiple aspects such as promoting blood circulation and removing blood stasis, replenishing qi and blood, and nourishing the liver and kidneys. It has a significant effect in treating femoral head necrosis of blood stasis and obstruction type, and has achieved very good beneficial technical effects through experiments. The relevant experimental data are as follows:

[0037] 1Case Source

[0038] This study selected 60 patients with spleen-kidney yang deficiency type femoral head necrosis who visited the inpatient department of osteonecrosis at Luoyang Orthopedic Hospital of Henan Province from January 2022 to October 2023 as the research subjects.

[0039] 2 Diagnostic criteria

[0040] The diagnostic criteria were developed based on the 2012 edition of the Expert Consensus on Diagnosis and Treatment Standards for Femoral Head Necrosis in Adults.

[0041] (1) Clinical symptoms, signs and medical history: joint pain mainly in the groin, buttocks and thighs, occasionally accompanied by knee pain, limited hip flexion, internal rotation and external rotation, often with a history of hip trauma, corticosteroid use, alcoholism and occupational history such as diving;

[0042] (2) X-ray changes: In the early stage of femoral head necrosis, the femoral head will show increased density (sclerosis) and translucent areas (cystic changes); as the disease progresses, a typical crescent sign will appear; in the late stage, the femoral head may collapse, the joint space may narrow, and severe bone and joint changes may occur, with sclerosis and cystic changes in the acetabulum being common;

[0043] (3) CT scan changes: sclerotic bands surrounding necrotic bone, repaired bone, or subchondral bone fractures can be seen in the femoral head;

[0044] (4) MRI signs: T1WI shows a band-like low signal in the necrotic area or T2WI shows a double-line sign;

[0045] (5) Radionuclide bone scan: In the early stage of necrosis, there is a perfusion defect (cold area); as the disease progresses, there is a cold area in the hot area, which is a "doughnut-like" change;

[0046] (6) Bone biopsy: showed that the empty pits of osteocytes in trabeculae accounted for more than 50% and involved multiple adjacent trabeculae, with bone marrow necrosis.

[0047] The diagnosis can be confirmed if two or more of the above six criteria are met. Except for (1) and (5), the diagnosis can be confirmed if one of (2, 3, 4, 6) is met.

[0048] 3 The staging criteria are based on the 2019 Association Research Circulation Osseuse (ARCO) osteonecrosis staging criteria, as shown in Table 1.

[0049] Table 1 ARCO staging of femoral head necrosis

[0050]

[0051]

[0052] The complexion, lips and skin color of blood stasis obstructing the collaterals are dark or pigmented, prone to ecchymosis, relatively rough skin with obvious dandruff, prone to bruises, irritable temperament and forgetfulness. Women often have dark eye sockets, dark nose, easy hair loss, dry skin or nails, dysmenorrhea, amenorrhea, or purple-black menstruation with clots, metrorrhagia. The pain is severe, refusing to press, and the location is fixed; the lips are dull or purple, the tongue is dark with petechiae or flaky ecchymosis, and varicose veins under the tongue. The pulse is thin and astringent.

[0053] 4 Inclusion criteria

[0054] (1) Meet the diagnostic criteria for femoral head necrosis;

[0055] (2) those receiving conservative treatment;

[0056] (3) The primary disease is cured or in a stable stage;

[0057] (4) Those who are not accompanied by bone metabolic diseases, ankylosing spondylitis, bone tumors, various arthritis and other bone diseases;

[0058] (5) Be at least 18 years old and have the capacity to act independently;

[0059] (6) Patients who voluntarily participate in clinical research and sign the informed consent form.

[0060] 5 Exclusion criteria

[0061] (1) The primary disease has not been effectively controlled or is in the active stage;

[0062] (2) Patients with femoral head necrosis who refuse conservative treatment;

[0063] (3) Patients with other internal and external diseases other than the primary disease who require long-term medication;

[0064] (4) Pregnant or lactating women;

[0065] (5) Those who are currently participating in clinical trials of other drugs;

[0066] (6) Those who dropped out of the study or were lost to follow-up due to various reasons.

[0067] 6 Research Groups

[0068] Patients with femoral head necrosis of blood stasis type who received conservative treatment in Henan Orthopedic Hospital of Luoyang, Henan Province from January 2022 to October 2023 were selected as the research subjects. Patients were numbered from 1 to 60 according to the order of visit, and random numbers were generated using SPSS27.0. Patients were divided into treatment group and control group according to the random grouping principle, with 30 cases in each group.

[0069] 7. Medication

[0070] Treatment duration: 12 weeks

[0071] Control group: Xianling Gubao.

[0072] Treatment group: Xianling Gubao (specific usage is the same as the control group) combined with the Chinese medicine soup prepared in Example 2 of the present invention, 200 ml each time, once in the morning and once in the evening.

[0073] 8. Efficacy evaluation criteria

[0074] Harris score of hip joint function and visual analogue scale (VAS pain score) were observed in the two groups before treatment and 12 weeks after treatment, and the differences between the two groups before and after treatment were compared and analyzed.

[0075] 9 Clinical efficacy evaluation

[0076] After treatment, the P values ​​of Harris score and VAS pain score were less than 0.05, and the difference between the two groups was statistically significant. The therapeutic effect of the treatment group was better than that of the control group. The clinical efficacy evaluation is shown in Table 2.

[0077] Table 2 Comparison of Harris score and VAS pain score

[0078]

[0079] 10 Animal Experiment Evaluation

[0080] Twenty-four 8-week-old SD rats were subjected to intravenous injection of lipopolysaccharide (0.2 mg / kg) combined with 7-day continuous gluteal muscle injection of methylprednisolone (40 mg / kg) to establish a steroid-induced femoral head necrosis model. After 8 weeks, the 24 rats were randomly divided into 3 groups, including a model group (8 rats), a control group (8 rats), and a treatment group (8 rats). The model group was given normal saline by gavage, the control group was given Xianling Gubao solution by gavage, and the treatment group was given Xianling Gubao combined with Pishen Yangxu decoction by gavage. Micro-CT was performed after 6 weeks of intervention. The trabeculae of the rats in the model group were sparse, disordered, and had trabecular fractures; the trabeculae of the rats in the control group were sparse, and some trabeculae were fractured; the trabeculae of the rats in the treatment group were neatly arranged. The blood stasis and collateral blocking Chinese herbal decoction played a protective role against bone destruction in rats with steroid-induced femoral head necrosis, such as Figure 1 shown.

[0081] 11. Safety Assessment

[0082] No adverse reactions occurred in the 60 patients during the treatment period, and no obvious abnormalities were found in vital signs, blood routine, urine routine, stool routine, electrocardiogram, liver and kidney function, and coagulation function after taking the medicine, indicating that the Chinese medicine of the present invention has good safety.

[0083] After repeated tests and practices, other embodiments all obtained the same or similar test results as Embodiment 2, which will not be described in detail one by one.

[0084] 12 Conclusion

[0085] It can be seen from the above that the present invention has abundant raw materials, simple preparation method, easy to take, low cost, good effect, and the components support each other. It has the effects of warming the kidney yang and tending to strengthen the spleen. The whole prescription not only has stable efficacy, but also good long-term efficacy, is not easy to recur, and is easily accepted by patients. It is effectively used to treat femoral head necrosis of spleen and kidney yang deficiency type. The Chinese medicine soup of the present invention, which is characterized by simplicity, convenience, low cost and effectiveness, not only conforms to the pathogenesis of femoral head necrosis, but also conforms to the theory of warming and tonifying the spleen and kidney in traditional Chinese medicine. It is an innovation in drugs for treating femoral head necrosis, and has huge economic and social benefits.

[0086] It should be pointed out that the above is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any technician familiar with the profession can make changes or modify the technical contents disclosed above into equivalent embodiments with equivalent changes without departing from the scope of the technical solution of the present invention, which all fall within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis, characterized in that: The invention is prepared from the following raw materials by weight: 10-20g of angelica sinensis, 7-13g of peach kernel, 7-13g of chuanxiong, 7-13g of red peony root, 4-8g of roasted liquorice root, 8-16g of prepared rehmannia root, 13-27g of curcuma zedoaria, 13-27g of triangularis lancea, 5-11g of earthworm, 10-20g of achyranthes bidentata, 8-16g of millettia reticulata, 10-20g of astragalus and 4-8g of liquorice root.

2. The Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis according to claim 1, characterized in that: It is made from the following raw materials by weight: 15g of Angelica sinensis, 10g of peach kernel, 10g of Chuanxiong, 10g of red peony root, 6g of roasted liquorice, 12g of Rehmannia glutinosa, 20g of Curcuma zedoaria, 20g of Tripterygium wilfordii, 8g of Eupolyphaga sinensis, 15g of Achyranthes bidentata, 12g of Millettia reticulata, 15g of Astragalus and 6g of Licorice.

3. The Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis according to claim 1, characterized in that: It is made from the following raw materials by weight: 10g of Angelica sinensis, 7g of peach kernel, 7g of Chuanxiong, 7g of red peony root, 4g of roasted liquorice, 8g of Rehmannia glutinosa, 13g of Curcuma zedoaria, 13g of Tripterygium wilfordii, 5g of Eupolyphaga sinensis, 10g of Achyranthes bidentata, 8g of Millettia spatholobi, 10g of Astragalus and 4g of Licorice.

4. The Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis according to claim 1, characterized in that: It is made from the following raw materials by weight: 20g of Angelica sinensis, 13g of peach kernel, 13g of Chuanxiong, 13g of red peony root, 8g of roasted liquorice root, 16g of Rehmannia glutinosa, 27g of Curcuma zedoaria, 27g of Tripterygium wilfordii, 11g of Eupolyphaga sinensis, 20g of Achyranthes bidentata, 16g of Millettia reticulata, 20g of Astragalus membranaceus and 8g of liquorice.

5. The method for preparing the Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis according to any one of claims 1 to 4, characterized in that: It can be made into decoction, pills, tablets, granules and ointments.

6. The Chinese medicine composition for treating blood stasis and collateral obstruction type femoral head necrosis according to claim 5, characterized in that: The preparation method of the water decoction is as follows: add 400-600 ml of water to the above raw material medicine, soak at 18-25°C for 15-25 minutes, then boil over high heat, then turn to low heat, boil for 20-30 minutes, filter, obtain filtrate, and set aside; add 300-400 ml of water to the filter residue, boil over high heat, then turn to low heat, boil for 10-15 minutes, filter, discard the filter residue, obtain filtrate, combine the two filtrates, and concentrate to 1 / 2-1 / 3 of the amount of water added twice to obtain the decoction.

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