CN114129660A - Special calcium tablet for perimenopausal women and preparation method thereof - Google Patents

Special calcium tablet for perimenopausal women and preparation method thereof Download PDF

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CN114129660A
CN114129660A CN202010917209.XA CN202010917209A CN114129660A CN 114129660 A CN114129660 A CN 114129660A CN 202010917209 A CN202010917209 A CN 202010917209A CN 114129660 A CN114129660 A CN 114129660A
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parts
calcium
perimenopausal women
tablet
preparation
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华子昂
刘敏如
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Liu Minru Research Institute Shenzhen Co ltd
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Liu Minru Research Institute Shenzhen Co ltd
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • 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
    • A61K36/02—Algae
    • A61K36/05—Chlorophycota or chlorophyta (green algae), e.g. Chlorella
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • A—HUMAN NECESSITIES
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    • 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)
    • 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)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/488—Pueraria (kudzu)
    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/489—Sophora, e.g. necklacepod or mamani
    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8969—Polygonatum (Solomon's seal)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction

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  • Health & Medical Sciences (AREA)
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Abstract

The invention determines the core gene target of calcium deficiency of perimenopausal women by using vital big data, and obtains a medicinal and edible plant formula for calcium supplement of the perimenopausal women by using network pharmacology big data screening, wherein the medicinal and edible plant formula is prepared from the following raw materials in parts by weight: 5-40 parts of rhizoma polygonati, 5-30 parts of sophora flower, 2-30 parts of wolfberry fruit, 2-30 parts of polygonatum, 2-20 parts of poria cocos, 2-30 parts of chlorella, 5-30 parts of kudzu root, 5-20 parts of maca and 2-20 parts of broadleaf holly leaf, and the food raw materials containing 800mg of calcium of 400-mangnolia officinalis are matched for use and prepared according to the following method: s1 micronizing radix Puerariae, maca, rhizoma Polygonati Odorati, Poria, and Folum Ilicis, breaking cell wall, and extracting functional components; centrifuging the S2 extract to obtain supernatant; s3 concentrating the supernatant, mixing with calcium material, flos Sophorae Immaturus, fructus Lycii, and Chlorella superfine powder; s4 granulating, aseptically processing, and preparing the special calcium tablet for perimenopausal women by a standard tablet pressing process. The calcium tablet is designed according to life big data, is prepared from medicinal and edible plant raw materials, and has simple preparation method.

Description

Special calcium tablet for perimenopausal women and preparation method thereof
Technical Field
The invention relates to a special calcium tablet for perimenopausal women and a preparation method thereof.
Background
Perimenopause is a period before and after menopause of women, is a normal physiological change period, is mainly caused by ovarian function decline, and has endocrine, biological and clinical characteristics related to menopause, and generally begins from about 45 years old to 1 year after menopause. Osteoporosis (OP) in perimenopausal women is mainly associated with a decline in ovarian function and a decline in estrogen levels in women during this period, a skeletal disease characterized by a decrease in systemic bone mass and destruction of the bone microstructure, which in turn leads to increased bone fragility and increased risk of fracture, due to a variety of causes.
At present, sex Hormone Replacement Therapy (HRT) is the first-line therapy for preventing and treating perimenopausal osteoporosis, but has the risk of increasing the incidence rate of cardiovascular and cerebrovascular diseases, invasive breast cancer, venous thrombosis diseases and the like, so that the clinical application of the HRT is limited.
The other method for preventing and treating perimenopausal osteoporosis is calcium supplement, but the current calcium supplement products supplement calcium and supplement calcium, and exogenous calcium is only added under the condition that the absorption and transformation mechanism of calcium is not completely understood, and other necessary conditions of calcium absorption are neglected, so that the absorption amount of calcium is far less than the daily requirement of calcium, and the situation that only calcium is not absorbed is caused.
Chinese patent CN201210422523.6 discloses a calcium preparation, its preparation method and application, the formulation is composed of calcium salt, vitamin D, vitamin K, mannitol and glucose. Chinese patent CN200910082672.0 discloses a micro-emulsion calcium preparation, a preparation method and application thereof, wherein a micro-emulsion structure is used as a carrier of a calcium source, and vitamins, lecithin and sorbitol are used in a matching manner. The calcium supplement formulas and products are only designed from the calcium absorption perspective, and the fundamental reason that the perimenopausal women cause bone metabolism abnormality due to endocrine imbalance is not specifically considered. Calcium is not supplemented aiming at the physiological characteristics of the perimenopausal women, and the osteoporosis problem of the perimenopausal women cannot be fundamentally solved. Such as: chinese patent CN201410634969.4 discloses a Chinese medicinal composition for treating perimenopausal syndrome, which comprises rehmannia root, anemarrhena rhizome, phellodendron bark, glossy privet fruit, epimedium, morinda root, white peony root, tuber fleeceflower stem, salvia miltiorrhiza and uncaria; chinese patent CN201610839832.1 discloses a cornu Cervi Pantotrichum powder for the treatment of perimenopausal syndrome, which is prepared from cornu Cervi Pantotrichum, parched rhizoma Dioscoreae, and colla Corii Asini; chinese patent CN201510998572.8 discloses an ointment for conditioning perimenopausal syndrome and a preparation method thereof, wherein the formula comprises donkey-hide gelatin, tortoise-shell glue, Chinese yam, medlar, mulberry, kudzu root, rhizoma polygonati, cinnamon, tuckahoe, spina date seed, rhizoma anemarrhenae, liquorice, walnut kernel, black sesame, rock candy and yellow wine;
the existing traditional Chinese medicine patents are all patents aiming at perimenopausal syndrome, but perimenopausal osteoporosis cannot be equivalently prevented and treated, the optimum medicine formula cannot be screened from a molecular mechanism if the specific mechanism of the perimenopausal osteoporosis cannot be effectively aimed at, and the effectiveness cannot be influenced necessarily due to the lack of scientificity.
Disclosure of Invention
Aiming at the defects of calcium supplement for the perimenopausal women, the invention determines the core gene target of the calcium deficiency of the perimenopausal women by using life big data, and obtains a medicinal and edible plant composition for calcium supplement for the perimenopausal women by using network pharmacology big data screening: 400-800mg calcium, 5-40 parts of rhizoma polygonati, 5-30 parts of sophora flower, 2-30 parts of wolfberry fruit, 2-30 parts of polygonatum, 2-20 parts of poria cocos, 2-30 parts of chlorella, 5-30 parts of radix puerariae, 5-20 parts of maca and 2-20 parts of broadleaf holly leaf are prepared according to the following method: s1 micronizing radix Puerariae, maca, rhizoma Polygonati Odorati, Poria, and Folum Ilicis, breaking cell wall, and extracting functional components; centrifuging the S2 extract to obtain supernatant; s3 concentrating the supernatant, mixing with calcium material, flos Sophorae Immaturus, fructus Lycii, and Chlorella superfine powder; s4 granulating, aseptically processing, and preparing the special calcium tablet for perimenopausal women by a standard tablet pressing process.
Preferably, the agitation leaching parameters are: the liquid-material ratio is 5-12, the extraction temperature is 90-boiling, the extraction time is 0.5-2 hours, and the extraction times are 1-2 times.
Preferably, the extracting solution is phosphate solution, so as to maintain the pH value of the extracting solution stable and adjust the calcium-phosphorus ratio to improve the calcium absorption and utilization efficiency.
Preferably, the supernatant is obtained using a continuous centrifugation technique, preferably a tube centrifuge.
Preferably, the calcium is a calcium-containing material as specified in food safety laws.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A special calcium tablet for perimenopausal women and a preparation method thereof, specifically comprises the following steps: s1 mixing the following raw materials: 5 parts of kudzu root, 5 parts of maca, 5 parts of rhizoma polygonati, 2 parts of polygonatum odoratum, 2 parts of poria cocos and 2 parts of broadleaf holly leaf are subjected to superfine grinding and then mixed according to the following proportion; s2 stirring and leaching, wherein the specific parameters are as follows: 0.1M phosphate solution (pH7.0), liquid-material ratio of 5, extraction temperature of 90 deg.C, extraction time of 0.5 hr, extraction frequency of 2 times, and microwave-assisted extraction to accelerate dissolution, wherein the extraction adopts tubular centrifuge to obtain supernatant, and rotation speed of 16000 rpm takes supernatant; s3 vacuum concentrating the supernatant, mixing with calcium carbonate material containing 600mg calcium, 5 parts of flos Sophorae Immaturus, 2 parts of fructus Lycii, and 2 parts of Chlorella micropowder; s4 granulating according to standard granulating process, performing aseptic treatment, and preparing calcium tablet for perimenopausal women according to tablet standard process.
Example 2
A special calcium tablet for perimenopausal women and a preparation method thereof, specifically comprises the following steps: s1 mixing the following raw materials: 30 parts of kudzuvine root, 20 parts of maca, 40 parts of rhizoma polygonati, 30 parts of fragrant solomonseal rhizome, 20 parts of tuckahoe and 20 parts of broadleaf holly leaf are subjected to superfine grinding and then mixed according to the following proportion; s2 stirring and leaching, wherein the specific parameters are as follows: 0.2M phosphate solution (pH7.0), liquid-material ratio of 12, boiling extraction at extraction temperature, extraction time of 2 hours, extraction times of 1 time, accelerated dissolution by using microwave-assisted extraction technology, obtaining supernatant by using a tubular centrifuge, and taking the supernatant at a rotation speed of 16000 rpm; s3 vacuum concentrating the supernatant, mixing with superfine powder of 800mg calcium chloride, 30 parts flos Sophorae Immaturus, 30 parts fructus Lycii, and 30 parts Chlorella; s4 granulating according to standard granulating process, performing aseptic treatment, and preparing calcium tablet for perimenopausal women according to tablet standard process.
Example 3
A special calcium tablet for perimenopausal women and a preparation method thereof, specifically comprises the following steps: s1 mixing the following raw materials: 10 parts of kudzu root, 10 parts of maca, 10 parts of rhizoma polygonati, 10 parts of polygonatum odoratum, 10 parts of poria cocos and 10 parts of broadleaf holly leaf are subjected to superfine grinding and then mixed according to the following proportion; s2 stirring and leaching, wherein the specific parameters are as follows: extracting with pure water at a liquid-material ratio of 5, an extraction temperature of 90 deg.C, an extraction time of 1 hr, and an extraction frequency of 2 times, accelerating dissolution by using microwave-assisted extraction technology, obtaining supernatant by using a tubular centrifuge, and obtaining supernatant at a rotation speed of 16000 rpm; s3 vacuum concentrating the supernatant, mixing with calcium carbonate containing 400mg calcium and calcium phosphate raw material containing 400mg calcium, 10 parts of flos Sophorae Immaturus, 10 parts of fructus Lycii, and 10 parts of Chlorella micropowder; s4 granulating according to standard granulating process, performing aseptic treatment, and preparing calcium tablet for perimenopausal women according to tablet standard process.
Clinical validation
Example 1, example 2, and example 3 were all clinically validated according to the following methods:
method (A)
Inclusion criteria for 1 case
Female, age 41-60 years old; the diagnosis standard of perimenopausal syndrome is met; the patients were tested voluntarily, and the medicine was taken on time and the doctor was given a double-visit at regular intervals.
2 exclusion criteria
Those under the age of 41 or over the age of 60; combined with primary diseases such as liver and kidney, cardiovascular and cerebrovascular diseases, hemopoietic disorder and the like, and psychonoses; bilateral ovariectomy, ovarian tumor and premature ovarian failure; essential hypertension, essential hypotension and chronic anemia; those who have used sex hormone drugs within approximately 3 months; if the medicine is not taken according to the regulation, the curative effect can not be judged; insufficient data and the like affecting the judgment of curative effect or safety.
3 clinical verification
Statistics is carried out on osteoporosis cases of perimenopausal women, and 20 cases are respectively treated by taking a calcium tablet alone as a control group and taking the calcium tablet of the embodiment as a verification group. The taking method comprises the following steps: a calcium tablet is taken 3 times a day according to the instruction; the calcium tablet of the embodiment of the invention is 2 tablets per time and 3 times a day; the administration is continued for 3 months.
Bone density measurement: the bone density of lumbar vertebrae L2-4 and left femoral neck Wards triangle of 2 groups of patients was measured by a dual-energy X-ray bone density measuring instrument before and after administration (3 months later).
The statistical method adopts SPSS 20.0 statistical software to perform data analysis, the measurement data is expressed by x +/-s, the comparison adopts t test, and the counting data comparison adopts x 2 test. P <0.05 indicates that the difference is statistically significant.
(II) verification result
Example 1 comparison of bone Density before and after administration (g/cm)3,Mean±SD）
Figure DEST_PATH_IMAGE002
Example 2 comparison of bone Density before and after administration (g/cm)3,Mean±SD）
Figure DEST_PATH_IMAGE004
Example 3 comparison of bone Density before and after administration (g/cm)3,Mean±SD）
Figure DEST_PATH_IMAGE006
The clinical verification result shows that: after the control group and the verification group are taken for 3 months, the bone density of lumbar vertebra and femoral neck is improved to different degrees. The calcium tablets of the invention have better effect on relieving perimenopausal osteoporosis than the calcium preparation of the control group by verifying that the bone density of the group is improved higher than that of the control group in each example, wherein the water average for improving the bone density of the verification group of the example 2 is higher than that of the examples 1 and 3, and the example 2 is a better formula ratio and a preparation process of the calcium tablets of the invention.
Any combination of the summary of the invention and the detailed description of the invention section above, including the description of the invention, is not intended to be limiting in any way and does not describe all aspects of the combination for the sake of brevity. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (6)

1. The special calcium tablet for perimenopausal women and the preparation method thereof are characterized in that the raw materials are mixed according to the following parts by weight to prepare a beverage: 400-800mg calcium, 5-40 parts of rhizoma polygonati, 5-30 parts of sophora flower, 2-30 parts of wolfberry fruit, 2-30 parts of polygonatum, 2-20 parts of poria cocos, 2-30 parts of chlorella, 5-30 parts of radix puerariae, 5-20 parts of maca and 2-20 parts of broadleaf holly leaf are prepared according to the following method: s1 micronizing radix Puerariae, maca, rhizoma Polygonati Odorati, Poria, and Folum Ilicis, breaking cell wall, and extracting functional components; centrifuging the S2 extract to obtain supernatant; s3 concentrating the supernatant, mixing with calcium material, flos Sophorae Immaturus, fructus Lycii, and Chlorella superfine powder; s4 granulating, aseptically processing, and preparing the special calcium tablet for perimenopausal women by a standard tablet pressing process.
2. The special calcium tablet for perimenopausal women and the preparation method thereof according to claim 1, wherein the stirring leaching parameters are as follows: the liquid-material ratio is 5-12, the extraction temperature is 90-boiling, the extraction time is 0.5-2 hours, and the extraction times are 1-2 times.
3. The special calcium tablet for perimenopausal women and the preparation method thereof according to claim 1, wherein the extract is preferably phosphate solution, the pH value of the extract is maintained to be stable, the ratio of calcium to phosphorus is adjusted to improve the calcium absorption and utilization efficiency.
4. The special calcium tablet for perimenopausal women and the preparation method thereof according to claim 1, wherein the supernatant is obtained by using a continuous centrifugation technology, preferably a tube centrifuge.
5. The special calcium tablet for perimenopausal women according to claim 1, wherein calcium is a calcium-containing raw material prescribed in food safety law, and its preparation method.
6. The special calcium tablet for perimenopausal women prepared by the method and the application thereof in calcium supplement for the perimenopausal women are protected.
CN202010917209.XA 2020-09-03 2020-09-03 Special calcium tablet for perimenopausal women and preparation method thereof Pending CN114129660A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105456711A (en) * 2014-02-11 2016-04-06 青岛华之草医药科技有限公司 Application of traditional Chinese medicine composition in preparation of medicine for treating postmenopausal osteoporosis
CN105641370A (en) * 2014-11-12 2016-06-08 上海中医药大学附属龙华医院 Perimenopausal syndrome treating traditional Chinese medicine composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105456711A (en) * 2014-02-11 2016-04-06 青岛华之草医药科技有限公司 Application of traditional Chinese medicine composition in preparation of medicine for treating postmenopausal osteoporosis
CN105641370A (en) * 2014-11-12 2016-06-08 上海中医药大学附属龙华医院 Perimenopausal syndrome treating traditional Chinese medicine composition

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
陈志霞: "绝经后骨质疏松症的中医药治疗进展", 中医药导报, vol. 13, no. 03, 31 March 2007 (2007-03-31), pages 94 - 96 *

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