WO2004089389A1 - Composition pharmaceutique utilisee dans la prevention et le traitement de l'osteoporose et preparation correspondante - Google Patents

Composition pharmaceutique utilisee dans la prevention et le traitement de l'osteoporose et preparation correspondante Download PDF

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WO2004089389A1
WO2004089389A1 PCT/CN2004/000328 CN2004000328W WO2004089389A1 WO 2004089389 A1 WO2004089389 A1 WO 2004089389A1 CN 2004000328 W CN2004000328 W CN 2004000328W WO 2004089389 A1 WO2004089389 A1 WO 2004089389A1
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pharmaceutical composition
calcium
composition according
osteoporosis
extract
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PCT/CN2004/000328
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English (en)
Chinese (zh)
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Hsiang Wang
Yulin Mao
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Nuliv Biomedicine Inc.
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Priority to CN200480009477.0A priority Critical patent/CN1771047A/zh
Publication of WO2004089389A1 publication Critical patent/WO2004089389A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/43—Cuscutaceae (Dodder family), e.g. Cuscuta epithymum or greater dodder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/234—Cnidium (snowparsley)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis

Definitions

  • the present invention relates to a pharmaceutical composition and a preparation method for preventing and treating osteoporosis, and in particular, to osteoporosis related to elderly and / or menopausal women. Background technique
  • Osteoporosis is a systemic disease in which the amount of bone tissue is reduced, the microstructure of bone tissue is changed, the bone load capacity is reduced, and the risk of fracture is increased. Osteoporosis occurs mostly in elderly and postmenopausal women. The initial manifestations are general body pain or low back and leg pain. In the later stage, as osteoporosis worsens, spinal deformities can occur. Fractures can occur under slight external force, or lung capacity can be reduced due to thoracic deformities, which affects cardiopulmonary function.
  • both of the above two categories are not ideal medicines for treating osteoporosis because they have many side effects, or can cause complications due to long-term use, or are expensive or have inaccurate curative effects. ''
  • the third class of drugs used to treat osteoporosis is based on the theory of traditional Chinese medicine. According to the TCM Kidney Deficiency Theory, osteoporosis is closely related to TCM Kidney Deficiency. Kidney deficiency bone pain is the main symptom. It presents low back pain, tibia and knee weakness, etc. These symptoms are also the main symptoms of osteoporosis.
  • the mechanism of Chinese medicine to prevent osteoporosis may be achieved through the systemic, multi-link and multi-path regulation of the body.
  • Kidney therapy can correct immune system dysfunction, restore hypothalamus-pituitary-target organ function activities, promote bone calcium deposition, and at the same time can inhibit bone resorption and accelerate bone formation, not only can Delay bone loss and even increase bone mass.
  • Fructus cnidii is a dry, mature fruit of the umbelliferous plant Cndium monnieri (L.) Cuss., which belongs to the Chinese herbal medicine of fruits, and contains effective chemical components in the coumarin class. Osthole and imperatorin.
  • Cnidium chinense has the effect of nourishing kidney and aphrodisiac in traditional Chinese medicine, and it can also prevent osteoporosis in postmenopausal women.
  • C. chinensis and its total coumarins have osteoporosis and steroid effects in ovariectomized rats.
  • Osteoporosis in rats has a significant preventive effect; its main active ingredient, osteophyte, can inhibit bone resorption and bone formation, prevent osteoporosis after ovariectomy, prevent bone loss, and maintain normal bone mass levels.
  • a medicine for treating bone hyperplasia which is composed of Angelica sinensis, Ligusticum chuanxiong, Baishao, Shudi, Eucommia ulmoides, Chuanduan, Wujiapi, Gusuibu, Guizhi, Panax notoginseng, Huangpi, broken paper, dodder, codonopsis, papaya, chinu, natural copper, hawthorn, earthen element, leopard bone or dog bone, musk are processed into powdery combination.
  • Patent Application No. 96116013.6 which discloses a medicine for treating bone hyperplasia, which contains raw rehmannia glutinosa, rehmannia glutinosa, Cuscuta chinensis, Polygonum sibiricum, Polygala chinensis, Achyranthes bidentata, Qin Wei, Heterophyllum officinalis, Xiangfu , Raw licorice, yam, barley and other traditional Chinese medicine.
  • Chinese Patent Application No. 96120912, 7 discloses a medicine for bone hyperplasia, which contains cooked land, psoralen, Epimedium, Cuscuta, Acanthus, Cistanche, male silk moth, salt Eucommia, golden retriever dog spine , Schisandra chinensis, Heliotrope, Huai Achyranthes, Safflower, Dog Bone Meal, Whole Worm, Angelica, Paeonia lactiflora, Licorice, Ginseng, Jujube, Poria, Cynomorium, Panax notoginseng, powder by weight of bead beads, Frankincense , Myrrh is made into extremely fine powder.
  • Chinese Patent Application No. 98120495. discloses a Chinese medicinal composition for treating bone hyperplasia, which contains Scutellaria baicalensis, Habitat, Codonopsis, Salvia, Cuscuta, Ligustrum, Angelica, Sanling, Chiba, Mulberry Branch, celestial celestial vine, hellebore, epimedium, cricket, chuanchuan, kudzu root, achyranthes bidentata, eucommia ulmoides, frankincense, myrrh, aconite, cinnamon, windbreak, licorice, sea breeze, ginseng, mature land, yinchen, Jujube and mangosteen.
  • X discloses a health preparation for the prevention and treatment of osteoporosis, consisting of bone meal, rehmannia glutinosa, yam, dogwood, wolfberry, dodder, angelica, Alisma, Poria, Chenpi, Codonopsis, Scutellaria baicalensis, Coriander shell, Chuanxiongzi, Muxiang, etc.
  • Chinese yearly Patent Application No. 02120834.4 discloses an oral Chinese patent medicine for treating orthopedic diseases, consisting of turtle plate, bone fragment tonic, velvet antler, Shudi, Sanqi, Eucommia ulmoides, wolfberry, Cuscuta chinensis, earthworm, myrrh, agarwood , Continuity, blood exhaustion, red ginseng, mandarin meat group prescriptions made of compatibility.
  • Patent Application No. 02119186. 7 discloses a medicine for preventing and treating fractures and osteoporosis, which uses lettuce seeds, agarwood, rice, frankincense, atractylodes and dodder seeds as raw materials.
  • Oral acute LD50 of total coumarin mice in Sheds' bed is 2. 44 soil 0.05 g / kg (see Chinese Materia Medica Vol. 5, p. 931, published by the State Administration of Traditional Chinese Medicine of the venue, May 1999), Because toxicity can be life-threatening, precise dose control must be used when the snake bed is used for treatment.
  • An object of the present invention is to provide a compound medicinal composition for preventing or treating osteoporosis and a method for manufacturing the same.
  • the medicinal composition contains a Chinese herbal medicine material, namely, a compound combination of a mixed extract of Cuscuta and Snake Bed And add additives known to those skilled in the art, such as one or more pharmacologically acceptable adjuvants and / or carriers and / or excipients.
  • This Chinese herbal medicine material can reduce the toxicity of the snake bed, but will not affect the effect of the snake bed on osteoporosis.
  • Another object of the present invention is to provide a unilateral pharmaceutical composition containing a Cuscuta extract, which is added with additives well known to those having ordinary knowledge in the art, and a method for manufacturing the same, which has the curative effect of preventing and treating osteoporosis.
  • Yet another object of the present invention is to provide a pharmaceutical composition for preventing or treating osteoporosis, which, in addition to containing Cuscuta, or Snake Bed and Cuscuta, further comprises a calcium-containing substance and / or vitamin D3 to improve Effectiveness in the prevention and treatment of osteoporosis.
  • Yet another object of the present invention is to provide a method for preparing a pharmaceutical composition for osteoporosis, comprising the following steps:
  • the method for preparing the pharmaceutical composition includes the following steps:
  • the pharmaceutical composition of the present invention is a mixture consisting of two traditional Chinese medicines, such as snake bed, dodder, and the like. After extraction and purification, a pharmaceutical composition containing a high amount of active ingredients (that is, coumarins and flavones) is produced.
  • active ingredients coumarins and flavonoids have been recognized by the world as having hormonal effects in plants, and have become one of the hotspots in osteoporosis research today.
  • the single-component extract of Cuscuta chinensis used in the present invention also has phytohormones such as coumarins and flavones.
  • the medicinal composition of the Cuscuta chinensis in combination with the snake bed has the effects of significantly increasing bone mineral density (Bone Mineral Density, BD), and significantly increasing the calcium and phosphorus content in the ashes.
  • bone mineral density Bismaleic Acid Density, BD
  • C active ingredient
  • the single plant extract of Cuscuta chinensis also has the same effect on the treatment of osteoporosis.
  • the single component extract of Cuscuta chinensis does not have any concern about toxicity and safety.
  • snake bed with Cuscuta extract separate Cuscuta extract, snake bed with Cuscuta extract and Cuscuta extract alone, plus calcium-containing substances and vitamin D3, it can increase bone mineral density and calcium and phosphorus content in ashes. Effect.
  • the medicinal composition comprises two traditional Chinese medicines, namely, Cushion Seed and Cuscuta.
  • Cushion Seed and Cuscuta the original medicinal materials of Cushion Seed and Cuscuta are very abundant, the price is relatively low, the content of active ingredients is high, and the quality is easy to control.
  • Cuscuta chincutus is Cuscuta chinensis Lara. It is a dry and mature seed, which belongs to the fruit Chinese herbal medicine. The effective chemical ingredients are quercetin and shannai in flavonoids. Kaerapferol and Cuscuta pharmacologically nourishes the liver and kidneys, treats luteal dysfunction, and regulates female reproductive endocrine disorders. Therefore, the use of Cuscuta in combination with snake bed is based on the traditional Chinese medicine. Osteoporosis is Associated with kidney deficiency, the flavonoids contained in Cuscuta chinensis have estrogen function and kidney-reinforcing effect. In addition to improving the curative effect of snake bed, it is also effective for osteoporosis.
  • the powdery extract obtained based on the above embodiment is dissolved in an appropriate amount of a solvent containing ethanol and poured into a pretreated D101 macroporous resin column (polystyrene non-polar column).
  • a pretreated D101 macroporous resin column polystyrene non-polar column.
  • water (10 L), 10% ethanol (10L), 50% ethanol (10L), and 80% ethanol (10L) are used to elute in order, the water extract is discarded, and the alcohol extract is decompressed. After concentration, 24 g of a product containing an active ingredient was obtained.
  • dodder material preferably in powder form, in a 5L container, and add 4-10 times the volume of 20% -80% ethanol (or other polar solvent), preferably 2800ml of 50% ethanol as extraction Solvent, at 50 ⁇ 70 Heating at ° o: TlO hours, then cooled and filtered. Next, the filtrate is concentrated under reduced pressure to a paste, and after adding 5% to 80% excipients (such as calcium carbonate and vitamin D3, etc.) (spray drying or freeze drying can also be used), the powder is dried and crushed to obtain a powdery form. Extracts.
  • 20% -80% ethanol or other polar solvent
  • 2800ml of 50% ethanol as extraction Solvent at 50 ⁇ 70 Heating at ° o: TlO hours
  • the filtrate is concentrated under reduced pressure to a paste, and after adding 5% to 80% excipients (such as calcium carbonate and vitamin D3, etc.) (spray drying or freeze drying can also be used), the powder is dried and crushed to obtain a powder
  • Example 2 the Cuscuta chinensis extract can be further purified.
  • the powdery extract obtained above was dissolved in an appropriate amount of a solvent containing ethanol, and poured into the top of a pretreated D101 macroporous resin column (polystyrene non-polar column), followed by water (10L) and 10% ethanol in this order. (10L), and 50% ethanol (10L) and 80% ethanol (10L), and the water extract is discarded. From the alcohol extract, 20 g of the active ingredient is obtained after concentration under reduced pressure.
  • the solvent or polar solvent used may be a single solvent or a polar solvent, or a mixture of two or more single solvents or a polar solvent.
  • Suitable solvents or polar solvents such as, but not limited to, water, alcohols and / or ketones.
  • the amount of liquid used is considered by those with ordinary knowledge in the art when implementing the invention.
  • Macroporous resin is a method for purifying and purifying impurities and concentrating active ingredients, and is known to those having ordinary knowledge in the art. Elution is performed in it, and the effective components are adsorbed, and then recovered by elution, and the effective components are separated.
  • the pharmaceutical composition of the invention comprising a snake bed and Cuscuta or a separate extract of Cuscuta and the addition of calcium-containing substances, respectively, can significantly increase the bone mineral density of the rat lumbar vertebrae, And significantly increase the calcium and phosphorus content in the femur ash.
  • the preferred ratio of Snake bed is about 20 to 80% by weight, more preferably about 30 to 70% by weight; and the preferred ratio of Cuscuta is about 20 to 80% by weight. More preferably, it is about 30 to 70% by weight.
  • Cuscuta chinensis is also effective on its own.
  • additives known to those skilled in the art such as adjuvants and / or excipients and / or carriers and / or stabilizers, may also be added.
  • Useful additives such as starch, dextrin, glucose and / or magnesium carbonate.
  • the pharmaceutical composition whether it is a single or a compound and a single or a compound plus a calcium-containing substance, can be made into a conventional dosage form, such as a cream, a dan, a pill, a powder, a capsule, a transdermal absorption patch , Long-acting sustained-release agents, nasal inhalants, sprays, liquids, injection powders, injections, namely solvents, granules, beverages and other pharmaceutical and food industry commonly used dosage forms and administration methods.
  • a conventional dosage form such as a cream, a dan, a pill, a powder, a capsule, a transdermal absorption patch , Long-acting sustained-release agents, nasal inhalants, sprays, liquids, injection powders, injections, namely solvents, granules, beverages and other pharmaceutical and food industry commonly used dosage forms and administration methods.
  • Add one or more calcium-containing substances such as calcium phosphates: such as calcium phosphate (monobasic), calcium phosphate (dibasic), anhydrous hydrogen phosphate (calcium phosphate, dibasic (anhydrous) )), Calcium phosphate (tribasic), and calcium lactate, calcium gluconolactate, calcium ascorbate, calcium oxide, calcium carbonate, Or calcium pantothenate, and / or vitamin D3, can enhance the therapeutic effect of the pharmaceutical composition of the present invention, and its addition ratio is 5 to 80% of the whole composition.
  • the aforementioned calcium-containing substances can also be used as additives such as adjuvants and / or carriers and / or excipients and / or stabilizers.
  • the pharmaceutical composition of the present invention has undergone safety tests on animal models, including in vivo toxicity tests, and found no oral acute lethal dose LD50.
  • oral dose reached 20,000 mg / kg, Its maximum has not been reached, and no test animals have died.
  • the animals were sacrificed, and important organs such as heart, liver, spleen, lung, kidney, and gastrointestinal tract were necropsied. No obvious abnormal changes were observed with the naked eye. This shows that there is no concern about the safety of oral toxicity of the pharmaceutical composition of the present invention compared to the use of the active ingredient snake bed alone.
  • the pharmaceutical composition of the present invention is provided by Viking Zhonghua (Shanghai) Biotechnology Co., Ltd., and its batch number is: 20020934
  • Retinoic Acid (RA) Lot No. 01006, Shanghai Sixth Pharmaceutical Factory
  • Calcium-containing substances calcium carbonate + vitamin D3
  • Preparation method Precisely weigh the appropriate amount of the test drug, formulate it with 0.5% sodium carboxymethylcellulose to the required concentration, and administer according to the volume of lml / 100g rats.
  • Source, species, strain, certificate of compliance Sprague-Dawley clean rat, purchased from Shanghai Xipuer-Bikai Laboratory Animal Co., Ltd.
  • mice Seventy-two healthy three-month-old male rats were randomly divided into 9 groups of 8 rats each. Each day within 15 days after the start of the experiment, the negative control group was given an intragastrically 0.5% CMC-Na solution, and the remaining groups were given 70 mg / kg retinoic acid. The rats in each group were orally given the following drugs sequentially for 5 weeks from the afternoon of the experimental day.
  • Negative control group 0.5% CMC-Na solution 10ml / kg
  • Cuscuta unilateral extract (referred to as Cuscuta unilateral)
  • Cuscuta chinensis unilateral 200mg / kg
  • Cuscuta unicorn + calcium-containing substance the ratio is 70/30: 200tng / kg in total
  • the results of bone mineral density analysis are shown in Table 1.
  • the pathological model group was compared with the negative control group (normal group), and it was found that the lumbar vertebrae and femur bone mineral density of the pathological model group rats were significantly reduced, indicating successful modeling.
  • the compound pharmaceutical composition containing snake bed and Cuscuta according to the present invention is 100 mg / kg, 200 mg / kg, 400 mg / kg dose group and Cuscuta single 200 mg / kg, compound low + calcium-containing substance 200 mg / kg, Cuscuta single + Compared with the pathological model group, the calcium-containing substance 200mg / kg was continuously administered for five weeks.
  • the compound pharmaceutical composition and the Cuscuta chinensis of the present invention have obvious effects after adding calcium-containing substances respectively.
  • the analysis results of the bone mineral content are shown in Table 2.
  • the pathological model group was compared with the negative control group (normal group), and the ash weight coefficient (ash weight / thousand weight) was found to decrease.
  • the contents of calcium and phosphorus in the ashes were significantly reduced.
  • the compound pharmaceutical composition of the present invention is 100mg / kg 200mg / kg 4G0mg / kg dosage group and Cuscuta unilateral extract 200mg / kg, compound low + calcium-containing substance 200mg / kg, Cuscuta unilateral + calcium-containing substance 200mg / kg
  • the 200 mg / kg 400 mg / kg, compound low + calcium-containing substance 200 mg / kg dose group significantly increased the calcium and phosphorus content in the femur ash.
  • Table 2 Effects of the pharmaceutical composition of the present invention on femoral ash weight coefficient and bone mineral content of retinoic acid-induced osteoporosis rats Treatment Method Dose Weight Weight Calcium Content Phosphorus Content
  • Negative control group 10 0. 588 soil 0. 142 + 0. 125 soil
  • Pathological model 10 0. 568 soil 0. 129 soil 0. 112 soil
  • Positive control group 3000 0. 574 soil 0. 148 + 0. 128 soil
  • the compound pharmaceutical composition and the compound of the present invention have low + calcium content, increase the calcium and rock content in the ashes, and have low toxicity.
  • the pharmaceutical composition of the present invention therefore has the medical effect of osteoporosis.
  • Bone morphometric indicators show that: compared with the control group, the percentage of femoral trabecular bone area and the average width of the trabecular bone of the model group rats are significantly reduced, indicating successful modeling; the compound medical composition of the present invention has high, medium and low compound + The percentage of trabecular bone area and the average width of trabecular bone in the three dose groups containing calcium were significantly higher than those in the model group, and the percentage of trabecular bone area in low doses was also significantly increased; Cuscuta unilateral extract and Cuscuta unilateral + calcium-containing substance The percentage of trabecular bone area and the average width of trabecular bone were significantly higher than those in the model group. See Table III.
  • Table 3 Effects of the pharmaceutical composition of the present invention on morphometric indicators of femur of retinoic acid-induced osteoporosis rats
  • the negative control was oval / fusiform, flatter, 0. 805 + 155. 33 + (same as the former) with smaller and smoother gaps. 047 *** 19. 38 *** The pathological model is narrow and long oval / narrow,
  • Compound low is narrow and long oval / long uneven,. 0. 785 + 51. 67 soil
  • Gap is smaller and smoother 0. 022 *** 9. 44 ***
  • Compound low + containing oval-shaped / long shuttle is more flat, 0. 881 soil 75. 87 +
  • Cuscuta is oval / long oval, slightly flat
  • Cuscuta is oval / long oval, slightly flat
  • the positive control was oval / fusiform, flatter, 0. 854 ⁇ 104. 67 + (same as the former) with smaller gaps and smoother 0. 033 ** 9. 69 ***
  • the high-dose and low-dose calcium-containing substance dose groups have the effects of increasing bone density and improving the trabecular shape of the osteoporosis model induced by retinoic acid in rats.
  • the low dose of the compound pharmaceutical composition of the invention and the Cuscuta chinensis extract and Cuscuta chinensis + calcium-containing substance also have a certain effect on retinoic acid-induced osteoporosis in rats.
  • Rats were anesthetized intraperitoneally with 20% urethane (urethane) 1 g / kg, fixed in the prone position, incisions were made on both sides of the back spine, and bilateral ovaries were removed under sterile conditions as a model of osteoporosis.
  • urethane urethane
  • rats a small piece of fat was removed from both sides of the sham operation group as a negative control.
  • 72 surviving healthy rats were randomly divided into 9 groups of 8 rats each, and the following drugs were orally administered:
  • Negative control group (sham operation): 0.5% CMC-Na solution 10ml / kg / d
  • Test drug group the pharmaceutical composition of the present invention
  • Cuscuta unilateral extract (referred to as Cuscuta unilateral)
  • Cuscuta chinensis unilateral 200mg / kg
  • the dried femur and tibia were carbonized and ashed in a 800 ⁇ horse-furnace for 6 hours.
  • the femoral ash weight was measured.
  • the ashes were then dissolved in a 6N HC1 solution to determine the bone Ca and P content.
  • the femoral ash weight coefficient (ash weight / dry weight) of the model group was significantly reduced. Although the calcium and phosphorus contents in the ash had a tendency to decrease, there was no statistically significant difference.
  • the high-dose and low-compound + calcium-containing substance dose groups significantly increase the femoral ash weight coefficient. See Table 4. ,
  • the DEXA test analysis results show that the bone mineral density of the femur and lumbar vertebrae of the model group rats is significantly reduced; the compound medicinal composition of the present invention has three high-dose, medium-dose, and low-dose groups; The substance dose group can significantly increase the bone mineral density of the femur, and the bone density of the lumbar vertebrae at a medium dose also increases significantly. See Table 5.
  • Bone morphometric indicators show that: compared with the control group, the percentage of femoral trabecular bone area and the average width of the trabecular bone of the model group rats are significantly reduced; the compound medicinal composition of the present invention is high, medium, low and compound low + calcium The percentage of trabecular bone area and the average width of trabecular bone of the four dose groups were significantly higher than those of the model group. The average width of trabeculae of Cuscuta unilateral and Cuscuta unilateral + calcium-containing substance was significantly higher than that of the model group. See Table 7.
  • the pathological model 10 is narrow or oval or uneven
  • the positive control 1 is oval or shuttle-shaped,
  • Cuscuta single 200 is long oval or long uneven
  • Cuscuta chinensis 200 is long oval or uneven.
  • the compound low 100 is narrow or oval or uneven
  • the compound 200 is oval or shuttle-shaped,
  • Compound height 400mg / oval or shuttle is flat, 0.9493 ⁇ 0. 142. 33 +
  • the compound medicinal composition of the present invention the unilateral Cuscuta chinensis, and the individual addition of calcium-containing substances have the effect of reducing bone conversion rate, can increase bone density, and improve morphology of bone trabeculae.
  • the ash weight coefficient was significantly reduced, and bone calcium and bone phosphorus were also reduced.
  • the dosage of high and low compound + calcium-containing substances can significantly increase the ash weight coefficient, and the bone calcium and bone phosphorus contents also increase to a certain extent.
  • the compound pharmaceutical composition of the present invention and the addition of calcium-containing substances can increase the bone mineral content in the femur, increase the hardness of the bone, reduce the chance of fracture, and improve the symptoms of osteoporosis.
  • This experiment shows that the pointers such as the ultimate strength of the model group are significantly reduced, and the ultimate strength of the compound pharmaceutical composition of the present invention and the doses of the calcium-containing substance and the Cuscuta unilateral and the calcium-containing substance are significantly increased, indicating that bone The bending resistance, impact resistance and fatigue resistance are improved compared with the model group.
  • the compound pharmaceutical composition of the present invention and the addition of various doses of calcium-containing substances, as well as the Cuscuta chinensis and the addition of calcium-containing substances can significantly improve the structure of bone trabecula, making it tend to be oval and shuttle Shape, the bone surface is smoother and smoother, the percentage of trabecular bone area and the average diameter of trabecular bone are significantly increased, indicating that the medicinal composition of the present invention and the addition of calcium-containing substance, Cuscuta unilateral and the addition of calcium-containing substance can significantly improve the ovarian removal. Rat bone structure.
  • the oral acute toxicity test of the pharmaceutical composition of the present invention 20 Kunming mice were selected, half male and half female. After fasting for 12 hours, the pharmaceutical composition was administered at 0.8 ml / 20 g (maximum dosing capacity), and the behavior of rats in 14 R was observed, and then the internal organs were dissected and analyzed. The results showed that the activity decreased after gavage, and normal activity returned to normal after 2 hours. In addition, the vital organs such as heart, liver, spleen, lungs, kidneys, and gastrointestinal tract were found by anatomy. The experimental results show that the oral dose of the pharmaceutical composition of the present invention is 20,000 mg / kg, but it has not reached its maximum.
  • the maximum tolerated amount of mice is more than 20,000 mg / kg.
  • 20 Kunming mice were selected, half male and half female. After fasting for 12 hours, the medicinal composition 0.8ml / 20g (maximum dosage of 50mg / ml) was intraperitoneally injected, and the movement behavior of the rats was observed within 14 days. Then, the internal organs were dissected and analyzed. The results showed that there was no abnormality in the activity after intraperitoneal injection.
  • the vital organs such as heart, liver, spleen, lung, kidney, and gastrointestinal tract were found by anatomy.
  • the experimental results show that the intraperitoneal injection amount of the pharmaceutical composition of the present invention is 2,000 mg / kg, but it has not reached its maximum value. Therefore, it can be inferred that the maximum tolerated amount of the mouse is more than 2,000 mg / kg.

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Abstract

L'invention concerne une composition pharmaceutique utilisée pour prévenir et traiter l'ostéoporose, ainsi que son mode de préparation. Ladite composition comprend Cuscuta sinensis lam., ou Fructus cnidii et Cuscuta sinensis lam., ses constituants actifs contiennent un niveau élevé de coumarine et de flavone après purification. Ladite composition pharmaceutique à base de Fructus cnidii et de Cuscuta sinensis lam. permet de renforcer distinctement la densité minérale des os et d'augmenter la teneur en calcium et en phosphore dans le calcium. En outre, ladite composition permet également de réduire la toxicité orale de Fructus cnidii. Ladite composition ne contenant que du Cuscuta sinensis lam. est également efficace. Par ailleurs, ladite composition pharmaceutique peut combiner calcium et/ou vitamine D3 pour renforcer les effets.
PCT/CN2004/000328 2003-04-11 2004-04-09 Composition pharmaceutique utilisee dans la prevention et le traitement de l'osteoporose et preparation correspondante WO2004089389A1 (fr)

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Application Number Priority Date Filing Date Title
CN200480009477.0A CN1771047A (zh) 2003-04-11 2004-04-09 用于预防或治疗骨质疏松症的医药组合物与制备方法

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CN03116352.1 2003-04-11
CNA031163521A CN1535714A (zh) 2003-04-11 2003-04-11 用于预防及治疗骨质疏松症的医药组合物与制备方法

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CN114272222A (zh) * 2021-12-23 2022-04-05 安徽悦博生物制药有限公司 一种参藿温肾胶囊制剂及其制备方法
CN115737729A (zh) * 2022-11-24 2023-03-07 新疆医科大学 一种治疗骨质疏松的民族药制剂及其制备方法

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