CN114129678A

CN114129678A - Traditional Chinese medicine formula for promoting calcium supplement of children

Info

Publication number: CN114129678A
Application number: CN202010917243.7A
Authority: CN
Inventors: 华子昂; 朱美瑛; 刘宝全; 万君兴; 竹添; 孙宁; 王姣
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-09-03
Filing date: 2020-09-03
Publication date: 2022-03-04

Abstract

Aiming at the calcium deficiency of children, the invention utilizes the vital data technology to excavate the key gene target of the calcium deficiency of children starting from the etiology mechanism, finds out the key compound for regulating and controlling the key gene target through the network pharmacological system tool, and screens the medicine-food homologous traditional Chinese medicine to form the traditional Chinese medicine formula for promoting the calcium supplement of children, wherein the traditional Chinese medicine formula is prepared from the following raw materials in parts by weight: 5-30 parts of dried orange peel, 5-30 parts of Chinese yam, 5-40 parts of white hyacinth bean, 3-20 parts of sharpleaf galangal fruit, 5-35 parts of gordon euryale seed and 6-25 parts of rhizoma polygonati. The traditional Chinese medicine formula is invented aiming at the osteoporosis caused by the special physiology of children, has the characteristics of target point-compound-traditional Chinese medicine correspondence, clear action mechanism and multi-dimensional system regulation, can promote calcium absorption by being taken alone, and can improve the calcium supplement effect by being matched with a calcium preparation.

Description

Traditional Chinese medicine formula for promoting calcium supplement of children

Technical Field

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine formula for promoting calcium supplement of children.

Background

The children are in the stage of rapid growth of bodies, and need a large amount of calcium for building bones and muscles, so the demand of calcium is very large, and the viscera of the children are delicate and tender in the development stage, the qi of the body is not filled, the healthy viscera function is not formed, the deficiency of the kidney, the spleen and the lung qi often appears, and the characteristics of delicate and tender lung, frequent insufficiency of the spleen and frequent deficiency of the kidney are shown. The absorption and utilization of calcium are limited, and calcium deficiency easily occurs.

At present, the most common method for supplementing calcium for children is to take calcium supplementing products. However, the existing calcium supplement products are only added with exogenous calcium (or added with vitamin D), which is to supplement calcium, and the exogenous calcium is only added under the condition that the absorption and transformation mechanism of calcium and the special physiological characteristics of children are 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. And the expert committee of vitamin D discipline group of the calcium deficiency committee of the chinese college of senior citizens pointed out: "the following dosing method has proven ineffective, or ineffective and the risk of poisoning increases, and therefore the use of active vitamin D formulations" is not recommended [ china journal of calcium deficiency 2014, volume 20, phase 9.

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 products are only designed from the calcium absorption angle, and do not supplement calcium according to the physiological characteristics and molecular mechanism of children, so that the problem of calcium deficiency of children cannot be fundamentally solved. The most suitable medicine formula is not screened from a molecular mechanism causing calcium deficiency of children, and the scientificity and the effectiveness are lacked.

In addition, the addition amount of calcium in the beverage specified in national food safety standard of food nutrition enhancer use (GB 14880-2012) is 160-1350 mg/kg, the daily consumption of the domestic calcium preparation related liquid food is about 100mL at present, the maximum addition amount of calcium limited by laws and regulations is only 135 mg, the requirement that the daily calcium intake of children is 1000-.

Disclosure of Invention

Aiming at the defects, the invention starts with a cause mechanism aiming at the calcium deficiency of children, utilizes a life big data technology to excavate a key gene target point of the calcium deficiency of the children, finds a key compound for regulating and controlling the key gene target point through a network pharmacological system tool, and screens a medicine-food homologous traditional Chinese medicine to form a traditional Chinese medicine formula for promoting the calcium supplement of the children, wherein the traditional Chinese medicine formula is prepared from the following raw materials in parts by weight: 5-30 parts of dried orange peel, 5-30 parts of Chinese yam, 5-40 parts of white hyacinth bean, 3-20 parts of sharpleaf galangal fruit, 5-35 parts of gordon euryale seed and 6-25 parts of rhizoma polygonati.

The traditional Chinese medicine formula disclosed by the invention takes the key gene for regulating and controlling the calcium deficiency of children as a core, focuses on the internal relation between the absorption and the utilization of calcium of children by taking the comprehensive endocrine regulation of children as an auxiliary, effectively grasps the key bone metabolism target of children by adopting big data analysis and network pharmacology analysis, and solves the calcium deficiency problem of children by regulating and controlling the key gene network, and the concrete basis is as follows.

(1) VD3 forms 25-OH-VD3 through 25-hydroxylase in the liver, and forms 1, 25- (OH)2-VD3 through 1 alpha-hydroxylase in the kidney, which is the real active form of vitamin D in the body and promotes the absorption of calcium ions in epithelial cells of small intestine into blood; when the blood calcium is high, one part of the calcium is discharged out of the body by urination, and the other part of the calcium is stored in bones under the action of Calcitonin (CT) (bone formation); when the blood calcium is insufficient, the bone calcium flows into the blood under the action of parathyroid hormone (PTH) (bone resorption) and is then excreted out of the body from urine, and the dynamic flow of calcium in the process, namely bone formation-resorption coupling, is responsible for the renewal of bone tissue.

(2) The children are in the stage of rapid growth of the body, the bone mass, size and structure of the children are greatly influenced by growth hormone and sex hormone, but the viscera are tender and the shape and qi are not filled at the moment, the healthy viscera function is not formed, the growth hormone in the body is at a high level, the sex hormone is at a low level, the absorption and utilization of calcium are influenced, and the calcium deficiency is easy to occur.

(3) Starting from the etiology mechanism of calcium deficiency of children, combining clinical gene data, and digging 191 key genes of calcium deficiency of children by using big data, see table 1.

TABLE 1 Key genes for calcium deficiency in children

PTGS1

F7

CCNB1

CTNNB1

ADRB2

SOD1

top2

CES1

BDNF

DNPEP

PTGS2

top2A

MPO

MYC

CHRNA2

CAT

MAPK3

SOAT1

PPARD

SLC6A3

HSP90AA1

NCOA2

AHR

CASP7

SLC6A4

NR1I2

MAPK1

PRSS3

CRP

LTA4H

NOS2

CALM1

IGF2

F3

OPRM1

PLA2G4A

LDLR

LPL

INS

SAA1

ESR1

DPP4

ALOX12

GJA1

GABRA1

ABCC2

BAD

NOS3

PLG

NCOA3

AR

PIK3CG

NFATC1

MMP10

CHRNA7

MTOR

MTTP

ATP5F1B

FABP1

IGHG1

PPARG

PDE3A

TDRD7

PGR

P450

LYZ

APOB

HP

RBP2

ADRA2A

RXRA

RELA

EGLN1

KCNH2

PRKCA

QPRT

PLB1

PDHX

GCG

AKR1B1

ESR2

AKT1

NOX5

DRD1

TGFB1

SLC6A2

HMGCR

MOGAT2

ENPEP

MAOA

MAPK14

VEGFA

APOD

CHRM3

PON1

TRPV1

CYP19A1

MAPK8

UChenPi2

CTRB1

GSK3B

BCL2

CASP9

CHRM1

MAP2

GABRA6

GSTP1

TIMP1

CCK

ADRB1

CDK2

FOS

MMP2

SCN5A

KCNMA1

ABAT

UGT1A1

CREB1

CITED1

PYY

CHEK1

BAX

JUN

GABRA2

NR3C2

ADH1A

PPARA

CD163

NTRK2

SERPINE1

PKACA

MMP9

CASP8

CHRM4

CTSD

F2

SREBF1

EPHB2

PDX1

GOT1

PRSS1

CASP3

MMP1

HTR2A

ADH1B

CHRM5

GSR

PLAU

SLC2A2

PKIA

PIM1

TP53

HMOX1

GABRA5

ADH1C

CA2

ABCC1

TEP1

PAM

CDKN1A

CCNA2

HIF1A

CYP3A4

ADRA1A

LACTB

ACHE

ADIPOQ

EDN1

SCD

ADRA1B

NCOA1

FOSL1

CYP2B1

GABRA3

MAOB

ADRA1D

SOAT2

ERBB2

UChenPi3

CAV1

CALM

FOSL2

CYP1A2

CHRM2

NR3C1

BACE1

AKR1C1

GAP43

CETP

CDC2

F10

(4) Another patent to the first invention of the present invention: a method for screening Chinese medicinal composition with network targeting function from molecular level (202010553171.2) comprises screening 34 active ingredients for regulating and controlling calcium deficiency key gene of children, and further screening 6 Chinese medicinal materials with optimal regulation and control according to the 34 active ingredients to form the composition.

The 34 active components for regulating and controlling the key genes of calcium deficiency of children: Z-Leu-OH, vitamin e, Stigmasterol, pipelongumine, nobiletin, nicotinic acid, naringenin, Syringaresinol-O-beta-D-glucoside, 4', 5-dihydroflavonone, 24-Methylolest-5-enyl-3 beta-O-glucopyranoside _ qt, 5,7-dihydroxy-2- (3-hydroxy-4-methoxyphenoxy) chroman-4-one, (2R) -7-hydroxy-2- (4-hydroxyphenoxy) chroman-4-one, Kadsuronone, isocucosterol, gynesine, resorcinoside C _ dit, D-Homoproline, DFV, Datascoside, clinol, Ciigatropine, citron-D-acetylsalicylic acid, Boc-3 ' -thioflavin, AIDS, N-3 ' -thioflavin, N-3-D-acetylsalicylic acid, N-D-acetyl-D-acetyltyr, D-.

Screening 6 traditional Chinese medicines which are correspondingly regulated and controlled optimally according to active ingredients: dried orange peel, Chinese yam, white hyacinth bean, sharpleaf galangal fruit, gorgon fruit and sealwort. The dosage of the traditional Chinese medicine is determined by combining clinical application, and the traditional Chinese medicine formula is finally formed, and the traditional Chinese medicine formula specifically comprises the following components: 5-30 parts of dried orange peel, 5-30 parts of Chinese yam, 5-40 parts of white hyacinth bean, 3-20 parts of sharpleaf galangal fruit, 5-35 parts of gordon euryale seed and 6-25 parts of rhizoma polygonati.

(5) The network pharmacological action of the traditional Chinese medicine formula for promoting calcium supplement of children is shown in figure 1. beta-carotene, EIC and oleic acid are common components of semen lablab album and semen euryales; diosgenin is common component of rhizoma Dioscoreae and rhizoma Polygonati; the sitosterol is the common component of pericarpium Citri Tangerinae, fructus Alpinae Oxyphyllae, and rhizoma Polygonati.

Network pharmacological analysis shows that in the formula, 5 active ingredients of dried orange peel act together with 67 target points, 11 active ingredients of Chinese yam act together with 74 target points, 7 active ingredients of white hyacinth bean act together with 80 target points, 3 active ingredients of sharpleaf galangal fruit act together with 32 target points, 6 active ingredients of gorgon fruit act together with 76 target points, and 9 ingredients contained in polygonatum rhizome act together with 88 target points.

(6) The analysis result of the formula-component-target action network shows that the function of the formula of the invention for promoting the calcium absorption of children is realized by multiple traditional Chinese medicines, multiple components and multiple targets; wherein, the Chinese yam, the rhizoma polygonati and the white hyacinth bean have numerous active ingredients and rich action targets, and are in a core position in an action network, and the 3 Chinese medicaments form the main body part of the action network; the gordon euryale seed, the dried orange peel and the sharpleaf galangal fruit contain fewer components and have high target specificity, and the gordon euryale seed, the dried orange peel and the sharpleaf galangal fruit have the function of supplementing main network; the 6 traditional Chinese medicines are matched to form the system regulation and control on the key target point of calcium deficiency of children. Network pharmacological analysis shows that the formula has a clear action target network, a clear molecular mechanism and a systematic network regulation and control effect.

(7) The traditional Chinese medicine research shows that: dried orange peel: regulating qi-flowing, invigorating spleen, eliminating dampness, and eliminating phlegm; chinese yam: tonifying lung and spleen, clearing away deficiency heat, and arresting discharge; white hyacinth bean: invigorating spleen, regulating stomach, clearing away summer-heat, and eliminating dampness; fructus alpiniae oxyphyllae: warming spleen and kidney, consolidating qi and arresting seminal emission; gorgon fruit: to strengthen kidney and check nocturnal emission, tonify spleen and check diarrhea; rhizoma polygonati: tonify qi, nourish middle-jiao, moisten heart and lung, strengthen tendons and bones, and tonify kidney. The 6 traditional Chinese medicines are used together to tonify the kidney and strengthen the spleen and strengthen the bones and muscles, and are suitable for children with calcium deficiency.

Therefore, the formula of the invention has reasonable design and clear mechanism, and is an innovation of the traditional Chinese medicine compatibility theory.

Has the advantages that:

the invention has the beneficial effects that: firstly, the invention finds the calcium deficiency key gene target of children from the etiology mechanism through a big data tool and a network pharmacology analysis method, further finds a compound for regulating the key gene target, screens candidate traditional Chinese medicines from the compound, optimizes and screens the compound to finally form the formula of the invention, the formula mining process forms a compact corresponding relation of gene-compound-traditional Chinese medicine-physical sign to form a regulation and control network of multiple targets, multiple compounds and multiple traditional Chinese medicines, and the molecular layer carries out systematic regulation and control on the physical sign from the physiological characteristics of children, so that the invention has the advantages of science, comprehensiveness and systematicness; the preparation prepared by the formula can be taken alone to promote calcium absorption, is matched with a calcium preparation to improve the calcium supplement effect, and solves the problem that the existing calcium preparation only supplements but does not absorb. Secondly, the traditional Chinese medicines in the formula are all homologous in medicine and food, and the traditional Chinese medicine composition has the advantages of safety and low cost.

Drawings

FIG. 1 is a network pharmacological diagram of a traditional Chinese medicine formula for promoting calcium supplement of children

In FIG. 1, the size of a node and the number of edges both represent direct action relationships between the node and other nodes, and the larger the node or the more the edges, the more important the node or the edges are in the network; in FIG. 1, the triangle nodes represent the Chinese medicine, the circle nodes represent the active ingredients, and the diamond nodes represent the gene; some of the compounds in FIG. 1 are labeled with numbers, and the compounds are shown in Table 2 in comparison with the numbers.

TABLE 2 comparison of Compounds with numbers

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 (A)

Example 1

A traditional Chinese medicine formula for promoting calcium supplement of children is prepared from the following raw materials in parts by weight: 20g of dried orange peel, 30g of Chinese yam, 5g of white hyacinth bean, 15g of sharpleaf galangal fruit, 15g of gordon euryale seed and 25g of rhizoma polygonati.

Example 2

A traditional Chinese medicine formula for promoting calcium supplement of children is prepared from the following raw materials in parts by weight: 30g of dried orange peel, 20g of Chinese yam, 10g of white hyacinth bean, 3g of sharpleaf galangal fruit, 5g of gordon euryale seed and 15g of rhizoma polygonati.

Example 3

A traditional Chinese medicine formula for promoting calcium supplement of children is prepared from the following raw materials in parts by weight: 5g of dried orange peel, 10g of Chinese yam, 40g of white hyacinth bean, 20g of sharpleaf galangal fruit, 20g of gordon euryale seed and 10g of rhizoma polygonati.

Example 4

A traditional Chinese medicine formula for promoting calcium supplement of children is prepared from the following raw materials in parts by weight: 15g of dried orange peel, 5g of Chinese yam, 20g of white hyacinth bean, 10g of sharpleaf galangal fruit, 35g of gordon euryale seed and 6g of rhizoma polygonati.

(II) functional verification of the product of the embodiment

A first part: preparation of traditional Chinese medicine formula for promoting calcium supplement of children

The traditional Chinese medicine formula for promoting calcium supplement of children is prepared by the following methods in example 1, example 2, example 3 and example 4:

s1 selecting pericarpium Citri Reticulatae, rhizoma Dioscoreae, semen lablab album, fructus Alpinae Oxyphyllae, semen euryales, and rhizoma Polygonati;

s2 weighing pericarpium Citri Reticulatae, rhizoma Dioscoreae, semen lablab album, fructus Alpinae Oxyphyllae, semen euryales, and rhizoma Polygonati according to formula ratio, adding 8-10 times of water, leaching at 97-98 deg.C for 1 hr, and filtering with 200 mesh sieve to obtain filtrate;

s3 adding 5-10 times of water into the residue, leaching at 97-98 deg.C for 1h, and filtering with 200 mesh sieve to obtain filtrate;

s4 mixing the filtrates, concentrating if necessary, precipitating, filtering with 200 mesh sieve, and collecting the filtrate;

s5, fixing the volume and mixing uniformly; meanwhile, according to the requirement, a proper amount of sweetening agent, acidity agent and essence and spice can be added to modify the taste.

S6 filtering, filling and sterilizing to obtain the finished product.

A second part: clinical concrete application verification

Inclusion criteria for 1 case

Age 1-5 years; short and small body and weak limbs; the standard of calcium deficiency diagnosis of children 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 1 year of age or over 6 years of age; other abnormal conditions exist during taking; 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

The calcium deficiency cases of children were counted, 20 cases were treated with the calcium preparation alone as a control group, the formulation of example 2 alone as a verification group 1, and the formulation of example 2 plus the calcium preparation as a verification group 2. The taking method comprises the following steps: a calcium preparation is administered 3 times a day according to the instructions; the formula of the invention in the embodiment 2 is 30 ml/time, and 3 times a day; 1 month is taken as 1 course of treatment, and 3 courses of treatment are continuously taken.

Bone density measurement: the bone density of lumbar vertebra L2-4 and left femoral neck Wards triangle of 2 groups of patients is measured by adopting a dual-energy X-ray bone density measuring instrument before taking and after taking.

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.

TABLE 3 comparison of bone Density before and after administration (g/cm)³，Mean±SD）

After the control group and the verification group take the medicine for 3 courses of treatment, the bone density of the lumbar vertebra and the femoral neck is improved to different degrees; wherein, the bone mineral density of the control group and the verification group 1 is improved slightly, which indicates that the calcium preparation or the formula of the embodiment 2 has a certain effect of relieving the calcium deficiency of children when the calcium preparation or the formula is taken alone; the bone density improvement level of the verification group 2 is obviously higher than that of the control group and the verification group 1, which shows that the formula of the invention has the calcium supplement effect when being taken alone, has the effect of promoting the postpartum calcium absorption when being used together with a calcium preparation, and the difference has statistical significance (P is less than 0.05).

The functions of the embodiment 1, the embodiment 3 and the embodiment 4 are the same as those of the embodiment 2, and the effects are similar.

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

1. The traditional Chinese medicine formula for promoting calcium supplement of children is characterized by being prepared from the following raw materials in parts by weight: 5-30 parts of dried orange peel, 5-30 parts of Chinese yam, 5-40 parts of white hyacinth bean, 3-20 parts of sharpleaf galangal fruit, 5-35 parts of gordon euryale seed and 6-25 parts of rhizoma polygonati.

2. The traditional Chinese medicine formula for promoting calcium supplement for children according to claim 1, wherein the traditional Chinese medicine formula contains 6 traditional Chinese medicines, 34 core compounds and 191 key gene targets closely related to calcium deficiency of children.

3. A core compound closely related to the promotion of calcium supplementation in children according to claim 2, wherein the compound comprises: Z-Leu-OH, vitamin e, Stigmasterol, pipelongumine, nobiletin, nicotinic acid, naringenin, Syringaresinol-O-beta-D-glucoside, 4', 5-dihydroflavonone, 24-Methylolest-5-enyl-3 beta-O-glucopyranoside _ qt, 5,7-dihydroxy-2- (3-hydroxy-4-methoxyphenoxy) chroman-4-one, (2R) -7-hydroxy-2- (4-hydroxyphenoxy) chroman-4-one, Kadsuronone, isocucosterol, gynesine, resorcinoside C _ dit, D-Homoproline, DFV, Datascoside, clinol, Ciigatropine, citron-D-acetylsalicylic acid, Boc-3 ' -thioflavin, AIDS, N-3 ' -thioflavin, N-3-D-acetylsalicylic acid, N-D-acetyl-D-acetyltyr, D-.

4. The traditional Chinese medicine composition for promoting calcium supplement for children as claimed in claim 1, wherein a calcium-containing food nutrition enhancer specified by food and drug safety laws with a calcium content of 400-800mg can be added to the composition to improve the calcium supplement effect for children.

5. The traditional Chinese medicine formula for promoting calcium supplement of children according to claim 1, wherein the traditional Chinese medicine formula can be used alone to improve calcium absorption.

6. The traditional Chinese medicine formula for promoting calcium supplement of children according to claim 1, which is characterized in that the traditional Chinese medicine formula can be used in combination with other calcium preparations to improve the calcium supplement effect.

7. Protects the application of a traditional Chinese medicine formula for promoting calcium supplement of children in the calcium supplement process of children.