Traditional Chinese medicine composition and traditional Chinese medicine preparation for yang deficiency and cold coagulation type osteoporosis

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition and a traditional Chinese medicine preparation for yang deficiency and cold coagulation type osteoporosis, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 4-20 parts of fructus lycii, 10-30 parts of herba epimedii, 2-10 parts of deer-horn glue, 4-15 parts of cortex cinnamomi, 3-12 parts of radix aconiti carmichaeli, 3-12 parts of poria cocos, 10-30 parts of radix astragali and 3-15 parts of rhizoma curculiginis. The traditional Chinese medicine compound disclosed by the invention takes yang warming and cold dispelling, kidney tonifying and bone strengthening, and qi replenishing and spleen strengthening as treatment rules, can comprehensively improve the symptoms of yang deficiency and cold coagulation type osteoporosis, such as intolerance of cold and cold limbs, waist and knee crymodynia, limb numbness and the like, and meanwhile, promotes bone formation, inhibits bone resorption and improves bone density. Compared with an existing treatment scheme, the compound is based on syndrome differentiation and treatment of traditional Chinese medicine, pays attention to overall conditioning, can flexibly add or reduce medicines, realizes individualized treatment and adapts to physiques and symptoms of different patients.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly to a traditional Chinese medicine composition and a traditional Chinese medicine preparation for yang deficiency and cold coagulation type osteoporosis. Background Art

[0002] Osteoporosis is a progressive, metabolic bone disease characterized by reduced bone mass and altered bone microstructure, which affects bone strength and increases the risk of fractures. Yang deficiency and cold coagulation type osteoporosis is a syndrome differentiation type of osteoporosis in traditional Chinese medicine, and its main symptoms include aversion to cold and cold limbs, cold pain in the waist and knees, limb numbness, etc. The existing western medicine treatments mainly focus on antiresorptive drugs and anabolic drugs, but the adverse reactions limit their long-term use. Traditional Chinese medicine believes that the core pathogenesis of yang deficiency and cold coagulation type osteoporosis is yang deficiency of the kidney and spleen and cold coagulation and blood stasis, and the treatment requires warming yang and dispelling cold, tonifying the kidney and strengthening bones, and replenishing qi and invigorating the spleen. However, the existing traditional Chinese medicine compound prescriptions have problems such as complex components, unstable curative effects, and insufficient toxicity control, and urgent optimization is needed. Summary of the Invention

[0003] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a traditional Chinese medicine composition and a traditional Chinese medicine preparation for yang deficiency and cold coagulation type osteoporosis. The composition mainly consists of wolfberry fruits, roasted epimedium, deer horn glue, cinnamon, prepared aconite root, poria cocos, astragalus membranaceus, and curculigo orchioides; among them, curculigo orchioides and epimedium are the monarch drugs, cinnamon, deer horn glue, astragalus membranaceus, and aconite root are the minister drugs, and wolfberry fruits and poria cocos are the assistant drugs. Clinical trials have shown that the traditional Chinese medicine compound prescription, with the principles of warming yang and dispelling cold, tonifying the kidney and strengthening bones, and replenishing qi and invigorating the spleen, can comprehensively improve the symptoms of yang deficiency and cold coagulation type osteoporosis, such as aversion to cold and cold limbs, cold pain in the waist and knees, limb numbness, etc., and at the same time promote bone formation, inhibit bone resorption, and increase bone density. Compared with the existing treatment plans, the compound prescription is based on the syndrome differentiation and treatment of traditional Chinese medicine, pays attention to overall conditioning, can flexibly add or subtract drugs to achieve individualized treatment, and adapts to the constitutions and symptoms of different patients. In addition, when the traditional Chinese medicine compound prescription is used to treat osteoporosis, it has the characteristics of multi-target and multi-pathway actions, has small side effects, high safety for long-term application, and can improve the microscopic structure of bones and increase bone strength, thereby reducing the incidence of fractures.

[0004] The present invention is achieved through the following technical solutions: On the one hand, a traditional Chinese medicine composition for yang deficiency and cold coagulation type osteoporosis is provided, characterized in that the raw materials of the traditional Chinese medicine composition, by weight, include 4 - 20 parts of wolfberry fruits, 10 - 30 parts of roasted epimedium, 2 - 10 parts of deer horn glue, 4 - 15 parts of cinnamon, 3 - 12 parts of prepared aconite root, 3 - 12 parts of poria cocos, 10 - 30 parts of astragalus membranaceus, and 3 - 15 parts of curculigo orchioides.

[0005] Preferably, the raw materials of the traditional Chinese medicine composition, by weight, include 4-5 parts of Chinese wolfberry, 10-20 parts of roasted epimedium, 2-6 parts of deer horn glue, 4-12 parts of cinnamon, 3-9 parts of prepared aconite root, 3-10 parts of poria cocos, 10-20 parts of astragalus membranaceus, and 3-10 parts of curculigo orchioides.

[0006] Preferably, the raw materials of the traditional Chinese medicine composition, by weight, include 4 parts of Chinese wolfberry, 10 parts of roasted epimedium, 2 parts of deer horn glue, 4 parts of cinnamon, 3 parts of prepared aconite root, 3 parts of poria cocos, 10 parts of astragalus membranaceus, and 3 parts of curculigo orchioides.

[0007] Preferably, the epimedium is roasted epimedium.

[0008] Preferably, the aconite root is prepared aconite root.

[0009] Also provided is a traditional Chinese medicine preparation for osteoporosis of yang deficiency and cold coagulation type, comprising the above traditional Chinese medicine composition.

[0010] Preferably, the dosage form of the traditional Chinese medicine preparation is powder, pill, granule, capsule, tablet, paste, medicinal liquor or mixture.

[0011] Beneficial effects

[0012] In the present invention, Chinese wolfberry, roasted epimedium, deer horn glue, cinnamon, prepared aconite root, poria cocos, astragalus membranaceus, and curculigo orchioides are selected and used in a certain proportion. This traditional Chinese medicine compound is based on syndrome differentiation and treatment of traditional Chinese medicine, focuses on overall conditioning, can flexibly add or subtract drugs to achieve individualized treatment, and adapts to the constitutions and symptoms of different patients. In addition, when treating osteoporosis, this traditional Chinese medicine compound has the characteristics of multi-target and multi-pathway action, has small side effects, high safety for long-term application, and can improve the microscopic structure of bones and increase bone strength, thereby reducing the incidence of fractures. Specific embodiments

[0013] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0014] Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention. The experimental methods without specific conditions noted in the following embodiments are usually carried out under conventional conditions or according to the conditions recommended by the manufacturers. Unless otherwise specified, all percentages, ratios, proportions or parts are by weight.

[0015] The reagents and raw materials used in the examples and comparative examples of the present invention can be obtained through commercial channels without special instructions.

[0016] Example 1: Preparation of Traditional Chinese Medicine Composition for Osteoporosis of Yang Deficiency and Cold Coagulation Type

[0017] 4 parts of wolfberry fruit, 10 parts of roasted epimedium, 2 parts of deer horn glue, 4 parts of cinnamon, 3 parts of prepared common monkshood daughter root, 3 parts of poria, 10 parts of astragalus membranaceus, 3 parts of curculigo orchioides.

[0018] Example 2: Preparation of Traditional Chinese Medicine Composition for Osteoporosis of Yang Deficiency and Cold Coagulation Type

[0019] 5 parts of wolfberry fruit, 15 parts of roasted epimedium, 3 parts of deer horn glue, 5 parts of cinnamon, 4 parts of prepared common monkshood daughter root, 6 parts of poria, 12 parts of astragalus membranaceus, 4 parts of curculigo orchioides.

[0020] Example 3: Preparation of Traditional Chinese Medicine Composition for Osteoporosis of Yang Deficiency and Cold Coagulation Type

[0021] 6 parts of wolfberry fruit, 20 parts of roasted epimedium, 4 parts of deer horn glue, 6 parts of cinnamon, 5 parts of prepared common monkshood daughter root, 9 parts of poria, 15 parts of astragalus membranaceus, 5 parts of curculigo orchioides.

[0022] Example 4: Preparation of Traditional Chinese Medicine Composition for Osteoporosis of Yang Deficiency and Cold Coagulation Type.

[0023] 4 parts of wolfberry fruit, 2 parts of deer horn glue, 4 parts of cinnamon, 3 parts of prepared common monkshood daughter root, 3 parts of poria, 10 parts of astragalus membranaceus, 3 parts of curculigo orchioides.

[0024] Example 5: Preparation of Traditional Chinese Medicine Composition for Osteoporosis of Yang Deficiency and Cold Coagulation Type.

[0025] 4 parts of wolfberry fruit, 10 parts of roasted epimedium, 2 parts of deer horn glue, 4 parts of cinnamon, 3 parts of prepared common monkshood daughter root, 3 parts of poria, 10 parts of astragalus membranaceus.

[0026] In the preparation of Examples 1 to 5, the above compositions are extracted with a solvent, concentrated and dried, and then auxiliary materials are added to make corresponding dosage forms; or the above compositions are directly pulverized into fine powder to make corresponding dosage forms.

[0027] Preparation method of capsule:[[]]

[0028] Pretreatment of prepared common monkshood daughter root: Add 10 times the amount of water and decoct first for 1 hour until the aconitine content < 0.01% (UV detection)

[0029] Co - extraction of main drugs: Mix roasted epimedium, curculigo orchioides with the remaining drugs (except deer horn glue), add 8 times the amount of 70% ethanol, reflux and extract 3 times at 80°C (2h / 1.5h / 1h), combine the extracts, and filter through a 400 - mesh sieve;

[0030] Treatment of deer horn glue: Melt it in a water bath at 60°C and mix it with the concentrated solution;

[0031] Drying and forming: Concentrate under reduced pressure to a relative density of 1.25 (60°C), and spray - dry (inlet air temperature 180°C / outlet air temperature 90°C) to obtain dry extract powder;

[0032] Preparation of capsules: Mix dry extract powder: microcrystalline cellulose: magnesium stearate at a ratio of 78:20:2, fill into No. 0 capsules, and each capsule contains 0.5 g of crude drug ± 5%.

[0033] Tablet preparation method

[0034] Raw material ratio: the same as in Example 1

[0035] Preparation process: Preparation of extract: Obtain dry extract powder according to the method in Example 1; Granulation: dry extract powder: pregelatinized starch: microcrystalline cellulose = 70:25:5 (weight ratio), mix and granulate by wet granulation with 85% ethanol (18-mesh sieve); Drying: Dry in a fluidized bed at 50 °C until the moisture content ≤ 5%; Tabletting: Tabletting machine parameters: punch diameter 8 mm, pressure 8 - 10 kN, tablet weight control: 0.3 g / tablet ± 3%; Coating with film coating: Film coating solution formula: hydroxypropyl methylcellulose (HPMC) 3%, polyethylene glycol 6000 0.5%, coating weight gain: 2 - 3%;

[0036] Quality indicators: Disintegration time limit: ≤ 30 minutes (General Principles of Chinese Pharmacopoeia), icariin content: ≥ 1.0 mg / tablet, hardness: 50 - 80 N.

[0037] Oral liquid preparation method

[0038] Raw material ratio: the same as in Example 1

[0039] Preparation process: Decoction and concentration: Decoct the medicinal materials with water 3 times (10 times / 8 times / 6 times the amount of water, 1.5 h / 1 h / 0.5 h)

[0040] Combine the decoction liquids, concentrate under reduced pressure to 1:1 (i.e., 1 mL is equivalent to 1 g of crude drug); Alcohol precipitation treatment: Add 95% ethanol to adjust the alcohol content to 60%, let stand for 24 hours and then filter; Blending and filling: Add flavoring agents: honey 5% (w / v), potassium sorbate 0.05%; Ultrafiltration and sterilization (0.22 μm membrane) and then fill into 10 mL ampoules; Sterilization: Sterilize by autoclaving at 115 °C for 30 minutes.

[0041] Quality indicators: pH value: 4.5 - 5.5; Relative density: 1.10 - 1.15 (25 °C); Microbial limit: Comply with the standards for oral liquid preparations in the Pharmacopoeia.

[0042] Preparation method of concentrated pills

[0043] Raw material ratio: the same as in Example 1

[0044] Preparation process: honey preparation: honey is diluted with 20% water, boiled and filtered (100 mesh sieve), and refined to a water content of 18-22%; pan-pill molding: drug powder: refined honey = 1:0.8-1.0 (first use the drug powder to make a mold, and then pan-pill layer by layer); pellet diameter: 3-4mm (each pill weighs about 0.1g); drying: gradient drying: 40℃→50℃→60℃ drying for 2 hours each; coating: talcum powder: beeswax = 9:1 mixed coating, weight gain 5%;

[0045] Quality indicators: Dissolution time: ≤2 hours; Moisture: ≤12%; Pill weight difference: within ±8%.

[0046] Preparation of Chinese medicine powder

[0047] Raw material ratio: same as Example 1

[0048] Preparation process: Ultrafine grinding: The mixed medicinal materials are ground at -40℃ to a particle size of ≤15μm (D90 value); Sterilization: Cobalt 60 irradiation sterilization (dose 8kGy); Packaging: Packaging in aluminum-plastic composite film bags, 3g±2% per bag; Sealed with nitrogen.

[0049] Quality indicators: Fluidity: Angle of repose ≤35°; Microbial limit: Total aerobic bacteria <1000 CFU / g; Main component retention rate: Icariin ≥95% (compared with raw materials).

[0050] Dosage form comparison table

[0051]

[0052] Clinical trials

[0053] Inclusion criteria: age 45 to 70 years old; meeting the diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Primary Osteoporosis (2017)"; bone density T value ≤ -2.5.

[0054] Exclusion criteria: patients with a history of taking drugs that affect bone metabolism in the past 3 months; patients with other diseases that affect bone metabolism, such as osteomalacia, rickets, chronic rheumatic arthritis, and those with movement dysfunction caused by fractures; patients with secondary osteoporosis; patients with poor compliance and inability to persist in treatment.

[0055] Main symptoms of TCM:

[0056] 1. Cold pain in the waist and back: Severe cold pain in the waist and back is aggravated by cold, relieved by warmth, not relieved by lying still, and limited in movement;

[0057] 2. Bone weakness and cold limbs: soreness and weakness in the waist and knees, stiff joints, cold limbs, and muscle cramps when exposed to cold;

[0058] Secondary symptoms:

[0059] 1. Fear of cold and curled up: cold body and limbs, like warmth and dislike cold, complexion Pale complexion and listless spirit;

[0060] 2. Inability to control urination: Clear and profuse urine, frequent urination at night, or enuresis;

[0061] 3. Tongue and pulse: Pale and plump tongue with tooth marks on the edges, white and slippery tongue coating, deep, slow, thready and unsmooth pulse.

[0062] 60 patients who met the above criteria were selected, including 29 males and 31 females, with an average age of 56 years. The patients were randomly divided into 6 groups, and there were no significant differences in data between groups. The above patients were treated with the drugs in Examples 1 - 5 and Xianling Gubao Capsules respectively. The patients in the Example groups were administered 1 dose per day, taken separately in the morning and evening, and the Xianling Gubao Capsule group was taken orally according to the instructions. 15 days was one course of treatment, and the treatment lasted for 2 courses. The blood alkaline phosphatase ALP (U / L), blood calcium Ca (mmol / L) and bone mineral density BMD (T value) of the patients were detected before and after treatment.

[0063] Efficacy criteria: Disappearance of clinical symptoms and increase in bone mineral density indicate marked efficacy; Improvement of clinical symptoms but no significant increase in bone mineral density indicates effective; No improvement in clinical symptoms indicates ineffective.

[0064] Data of the patients before and after treatment are as follows:

[0065]

[0066]

[0067] Test conclusion: The efficacy of the Example 1 group is better than that of the Example 2, 3, 4, 5 groups and the Xianling Gubao Capsule group, which can effectively inhibit bone resorption, increase the blood calcium content and bone mineral density value; and when the monarch drug is missing, the clinical efficacy of the compound is significantly lower than that of other groups.

[0068] Typical case:

[0069] Patient Zhang, female, 68 years old;

[0070] Chief complaint: Repeated cold pain in the lumbar spine for more than 3 years, aggravated by 1 month with stiffness and coldness in both knees.

[0071] History of present illness: The patient had cold pain in the lumbar spine without obvious cause 3 years ago, which was aggravated in rainy or overcast weather or after fatigue. The symptoms have worsened in the recent 1 month. The cold pain in the lumbar spine is heavy and feels like being wrapped in ice, with limited movement. There is stiffness in the joints in the morning, soreness and weakness in both knees. She needs to lean on a cane when walking, curls up in bed at night due to fear of cold and needs to cover with a thick quilt. She has frequent urination at night (3 - 4 times / night), with clear and profuse urine. Poor appetite and loose stools.

[0072] Physical examination: Conscious, complexion Pale, cold limbs, widespread percussion pain in the lumbosacral region (+), bilateral straight leg raising test (-). Pale and plump tongue with tooth marks on the edges, white and slippery tongue coating; Deep, slow, thready and unsmooth pulse.

[0073] Auxiliary examination: Bone density test showed that the T value of L1-4 vertebrae was -2.8; Lumbar spine X-ray showed vertebral wedge deformation and sparse trabeculae.

[0074] Diagnosis: Osteoporosis (syndrome of yang deficiency and cold congelation)

[0075] Treatment process: Treated with the drug in Example 1. Initial diagnosis (the first course of treatment): After taking the medicine for 15 doses, the cold pain in the lumbar spine was slightly reduced, the morning stiffness was significantly improved, the nocturia was reduced to 2 times, and the stools gradually became formed.

[0076] Follow-up visit (the second course of treatment): All symptoms of the patient were significantly improved. Since the effect was good, the same prescription was continued. After taking 15 more doses, all symptoms disappeared, and the T value of the bone density reexamination increased to -2.51.

[0077] Efficacy determination: Marked effect.

[0078] In order to obtain a more effective proportioning, based on clinical experience and the idea of monarch-minister compatibility, this application focused on four herbs, the monarch herbs (Curculiginis Rhizoma, Epimedii Folium Praeparatum) and the key minister herbs (Cinnamomi Cortex, Aconiti Lateralis Radix Praeparata (processed)), and set 3 dosage levels for compatibility optimization. Verification was designed and completed with an animal model as the object:

[0079] Table 1: Orthogonal test factors and level design (unit: part)

[0080]

[0081]

[0082] Table 2: Orthogonal test plan (L9(3 4 ))

[0083]

[0084] The efficacy verification indicators are as follows:

[0085] 1. Warming the kidney and invigorating yang: Serum testosterone level and sperm motility of rats;

[0086] 2. Anti-fatigue: Load-bearing swimming time and lactate dehydrogenase activity of mice;

[0087] 3. Immunomodulation: Phagocytosis rate of peritoneal macrophages and IL-2 level of mice;

[0088] 4. Safety: Acute toxicity test (LD50), liver and kidney function indicators.

[0089] (Weight of each index: Warming the kidney and invigorating yang accounts for 50%, anti-fatigue 30%, immunity 20%)

[0090] Table 3: Pharmacodynamic evaluation indicators

[0091]

[0092]

[0093] Through experiments, the compatibility of the best combination verification group is as follows: Epimedii Folium Praeparatum 10, Cortex Cinnamomi 4, Aconiti Lateralis Praeparata 3, Rhizoma Curculiginis 3, fixed compatibility: Fructus Lycii 4, Colla Cornus Cervi 2, Poria 3, Radix Astragali 10

[0094] Table 4: Example of the effects of the best ratio verification group

[0095]

[0096] In summary, the composition of Fructus Lycii, Epimedii Folium Praeparatum, Colla Cornus Cervi, Cortex Cinnamomi, Radix Aconiti Lateralis Praeparata, Poria, Radix Astragali, and Rhizoma Curculiginis selected in the present invention can jointly exert the effects of warming yang and dispelling cold, tonifying fire and assisting yang, tonifying the kidney and strengthening bones, and replenishing qi and strengthening the spleen. Warming yang and dispelling cold can relieve the symptoms of aversion to cold and cold limbs, and cold pain in the waist and knees caused by cold pathogen stagnation; tonifying fire and assisting yang can dispel cold dampness and dredge the meridians, thus relieving limb numbness, pain, subsiding edema, and improving the quality of patients' daily life; tonifying the kidney and strengthening bones can promote the generation of kidney essence, nourish bones, inhibit bone loss, and enhance bone density; replenishing qi and strengthening the spleen can supplement the middle qi, improve the symptoms of spleen deficiency such as weakness due to qi deficiency and loose stools, enhance the body's vital qi, and improve the disease resistance. Among them, the monarch drugs Rhizoma Curculiginis and Epimedii Folium Praeparatum warm the kidney yang and replenish the marrow and strengthen the bones; the ministerial drugs Cortex Cinnamomi, Aconiti Lateralis Praeparata, etc. assist yang and dispel cold, promote blood circulation and relieve pain; the combination of all drugs jointly exerts the effects of "warming the life gate, expelling cold stasis, and strengthening the muscles and bones", enabling the kidney yang to be restored, the marrow to be filled, the bones to be strong, and the cold stasis to be removed, treating both the symptoms and the root causes, and can effectively improve the related symptoms of osteoporosis of yang deficiency and cold coagulation type, and promote the recovery of patients.

[0097] Compared with the existing treatment plan, this compound prescription is based on the syndrome differentiation and treatment of traditional Chinese medicine, pays attention to overall conditioning, can flexibly add or subtract drugs, realizes individualized treatment, and adapts to the constitutions and symptoms of different patients. In addition, when treating osteoporosis, traditional Chinese medicine compound prescriptions have the characteristics of multi-target and multi-pathway effects, with small side effects, high safety for long-term application, and can improve the microscopic structure of bones and increase bone strength, thereby reducing the incidence of fractures.

[0098] Finally, it should be noted that the above are only the preferred embodiments of the present invention and are not used to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for osteoporosis of yang deficiency and cold coagulation type, characterized in that, The raw materials of the traditional Chinese medicine composition, by weight, include 4-20 parts of wolfberry fruits, 10-30 parts of epimedium, 2-10 parts of deer horn glue, 4-15 parts of cinnamon, 3-12 parts of aconite, 3-12 parts of poria cocos, 10-30 parts of astragalus membranaceus, and 3-15 parts of curculigo orchioides.

2. The traditional Chinese medicine composition for yang deficiency and cold coagulation type osteoporosis according to claim 1, wherein, The raw materials of the traditional Chinese medicine composition, by weight, include 4-5 parts of wolfberry fruits, 10-20 parts of epimedium, 2-6 parts of deer horn glue, 4-12 parts of cinnamon, 3-9 parts of aconite, 3-10 parts of poria cocos, 10-20 parts of astragalus membranaceus, and 3-10 parts of curculigo orchioides.

3. The traditional Chinese medicine composition for osteoporosis of yang deficiency and cold coagulation type according to claim 2, wherein, The raw materials of the traditional Chinese medicine composition, by weight, include 4 parts of wolfberry fruits, 10 parts of epimedium, 2 parts of deer horn glue, 4 parts of cinnamon, 3 parts of aconite, 3 parts of poria cocos, 10 parts of astragalus membranaceus, and 3 parts of curculigo orchioides.

4. The traditional Chinese medicine composition for yang deficiency and cold coagulation type osteoporosis according to any one of claims 1 to 3, characterized in that, The epimedium is roasted epimedium.

5. The traditional Chinese medicine composition for yang deficiency and cold coagulation type osteoporosis according to any one of claims 1 to 3, characterized in that, The aconite is prepared aconite root.

6. A traditional Chinese medicine preparation for osteoporosis of yang deficiency and cold coagulation type, characterized in that, It contains the traditional Chinese medicine composition according to any one of claims 1-5.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, The dosage form of the traditional Chinese medicine preparation is powder, pill, granule, capsule, tablet, plaster, medicinal liquor or mixture.

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