CN111249305B

CN111249305B - Application of HgS in preparation of medicine for replacing zotara

Info

Publication number: CN111249305B
Application number: CN202010206075.0A
Authority: CN
Inventors: 赵晓辉; 张婷; 岳会兰; 周国英; 魏立新; 陈晨; 陶吉红; 贾文静
Original assignee: Northwest Institute of Plateau Biology of CAS
Current assignee: Northwest Institute of Plateau Biology of CAS
Priority date: 2020-03-23
Filing date: 2020-03-23
Publication date: 2022-04-12
Anticipated expiration: 2040-03-23
Also published as: CN111249305A

Abstract

The invention relates to application of HgS in preparation of a medicine for replacing zotara, and belongs to the technical field of medicine preparation. The application of the invention can realize the replacement of HgS for Zodiac, increase the entering of drugs into cells to achieve the synergistic effect, save a large amount of labor cost and raw material cost, and increase the economic benefit of enterprises.

Description

Application of HgS in preparation of medicine for replacing zotara

Technical Field

The invention relates to the technical field of medicine preparation, in particular to application of HgS in preparation of medicines for replacing zotara.

Background

HgS is the main component of Tibetan medicine Zuotai, which plays an important role in national medicine and is still used at present, and is an indispensable component of many prescription drugs. In the Tibetan medicine system, zolpidem is widely used as an adjuvant in a plurality of Tibetan medicine compound medicines. Drugs containing mercuric sulfide play an important role in national medicine. However, the Zodiac is prepared from hydrargyrum through a complex process, and the processing processes of various enterprises are different, so that the Zodiac has different qualities. The processing period is about 40 days, the time and the labor are wasted, but the high-efficiency alternative medicine is not provided at present.

Disclosure of Invention

The invention aims to provide application of HgS in preparation of medicines for replacing zotara. The application of the invention can realize the replacement of HgS for Zodiac, increase the entering of drugs into cells to achieve the synergistic effect, save a large amount of labor cost and raw material cost, and increase the economic benefit of enterprises.

The invention provides application of HgS in preparation of a medicament instead of zotara.

The invention also provides the application of HgS in preparing the medicine for enhancing the effect of the compound medicine by replacing zotara.

Preferably, the HgS has a purity of 99% or more.

Preferably, the HgS is cryogenically ground or water-milled prior to preparation; the cryogenic grinding comprises ice bath grinding or liquid nitrogen grinding.

Preferably, the HgS replaces zotare according to 1/10-2 times of zotare dosage.

Preferably, the compound medicine is a medicine containing zotaro.

Preferably, the compound medicine comprises seventy-ingredient pearl pills and/or Renqingchang.

Preferably, the mass ratio of the compound medicine to HgS is (5-20000): 1.

Preferably, the dosage form of the medicament comprises powder or granules.

Preferably, the medicine also comprises pharmaceutically acceptable auxiliary materials, and the auxiliary materials of the granules comprise starch, milk and/or hydroxymethyl cellulose.

The invention provides application of HgS to substitute for zotaro drugs. The application of the invention can realize the replacement of HgS for Zodiac, and particularly can increase the effect of increasing the medicine entering the cell to achieve the synergistic effect, thereby saving a large amount of labor cost and raw material cost and increasing the economic benefit of enterprises. Test results show that HgS can promote the pharmacodynamic ingredients of the seventy-ingredient pearl pills of the Tibetan medicine compound medicine to enter HN4 and K562 cells, and the effect of HgS on promoting the medicine to enter the cells is equivalent to that of the effective ingredients of the compound medicine of Zodiac; the HgS can promote the pharmacodynamic components of the renqingchang jujue of the Tibetan medicine compound medicine to enter HN4 and K562 cells, and the HgS has the same effect as that of the effective components of the Zote Pair compound medicine in promoting the medicine to enter the cells; HgS and zotaro reach synergistic effect by increasing the medicine entering into the cell, and HgS can replace zotaro in the aspect of promoting the medicine to enter the cell.

Drawings

FIG. 1 is a diagram showing the effect of HgS and zotara on promoting the effective ingredients of seventy pearl pills to enter HN4 cells provided in example 1 of the present invention;

fig. 2 is a diagram showing the effect of HgS and zotara on promoting seventy ingredient pearl pill drug effective ingredients to enter K562 cells provided in example 1 of the present invention;

FIG. 3 is a graph showing the effect of HgS and zotara on promoting entry of effective components of Renzhongjue into HN4 cells according to example 1 of the present invention;

fig. 4 is a graph showing the effect of HgS and zotara on promoting entry of renqingchangjue medicinal components into K562 cells provided in example 1 of the present invention.

Detailed Description

The invention provides application of HgS in preparation of a medicament instead of zotara. The application of the invention can solve the problems of uneven quality and time and labor waste in processing of the Zote-Temminck et Schaeffen.

In the present invention, the purity of HgS is preferably 99% or more. The source of the HgS is not particularly limited in the present invention, and a conventional HgS commercially available product well known to those skilled in the art may be used, and is preferably commercially available red mercury sulfide.

In the present invention, the HgS is preferably cryogenically ground or water-in-the-air treated prior to preparation; the cryogenic grinding comprises ice bath grinding or liquid nitrogen grinding. The water-jet method is not particularly limited in the present invention, and a water-jet method known to those skilled in the art may be used, for example, adding purified water to grind, collecting the upper suspension, and repeatedly grinding and collecting to remove large particles HgS.

In the invention, the HgS preferably replaces zotare by 1/10-2 times of zotare dosage, and more preferably 1/4-2/3.

In the invention, the compound medicine is all medicines comprising zotaro, and preferably, the compound medicine comprises seventy-ingredient pearl pills and/or benevolence normal sense.

In the invention, the mass ratio of the compound medicine to HgS is preferably (5-20000): 1, and the invention more preferably meets the condition that HgS replaces zotara according to 1/10-2 times of zotara dosage. In the verification process, the seventy-flavor pearl pills and/or the kernel constant sense with the removed zolpidem components are preferably used for verification. The invention preferably takes two Tibetan medicine finished medicines to be crushed, methanol and the medicines are subjected to ultrasonic extraction for 3 times at the temperature of 1: 3-1: 10 and 30-70 ℃, centrifugal filtration is carried out at the speed of 1000-2000 r/min, and supernate is taken to remove the added zolpidem in the finished medicines.

In the present invention, the dosage form of the drug preferably includes powder or granules.

In the invention, the medicament also comprises pharmaceutically acceptable auxiliary materials, and when the medicament is in a powder form, the auxiliary materials are not required to be added; when the dosage form of the medicament is granules, starch, lactose and/or hydroxymethyl cellulose are preferably added.

In the invention, in the medicine prepared by the application, the effective in-vitro dosage of the HgS is preferably 1 ng/ml-2 mu g/ml (mainly considering that the HgS is added according to 1/10-2 times of the zotaro content in the original medicine, and the amount of the HgS is not specially specified); the effective in vivo dosage is preferably 10 ng/ml-100 ng/ml, and the in vivo administration is preferably 1 time of HgS every 1-7 days. In the present invention, Renqingchangjue and seventy-ingredient pearl pills are used according to clinical dosage.

The following examples are provided to further illustrate the use of HgS in the preparation of a medicament in place of zolpidem in the present invention, and the technical solutions of the present invention include, but are not limited to, the following examples.

Example 1

Seventy-ingredient pearl pills and Renqingchang extract: pulverizing the two Tibetan medicines, ultrasonically extracting the medicines with methanol at a ratio of 1: 3-1: 10 for 3 times, centrifuging at a speed of 1000-10000 r/min, and filtering with supernatant filter paper or microporous filter membrane to remove the radix bupleuri components added in the Tibetan medicines to obtain an extract for later use.

In vitro drug entry promotion experiments: HN4 and K562 cells are plated for 60 thousands, 6ml of DMEM/F-12 culture solution is added into HN4, K562 cells are added into RPMI1640 culture solution for 24 hours and then are sucked away, more than 10ml of two culture solutions are respectively added, 500ul of seventy-flavor pearl pill extract is respectively added into HN4 and K562 cells, the final administration concentration is 100ug/ml, 500ul of Renqing normal sense extract is respectively added into HN4 and K562 cells, the final administration concentration is 30ug/ml, the ratio of the two drugs to the Zote or HgS is 100: 1-40000: 1, the dosage ratio of Zote to HgS is 10: 1-1: 2, 300 ul of Zote is added, the cells are collected after 24 hours, 48 hours and 72 hours respectively, the cells are centrifuged for 5min, the rotating speed is 1000rpm, supernatant is discarded, PBS is used for 3 times to remove extracellular drugs, 10 ul of lysate is added into the precipitate, then the cells are lysed for 1min, and the cells are ultrasonically extracted by 1ml of methanol, and (5) absorbing peak areas of the effective components of the two medicines in the membrane passing liquid phase detection, and injecting 100 mu l of liquid phase.

The results are as follows:

HgS can promote the medicinal components in the seventy-ingredient pearl pills of the Tibetan medicine compound medicine to enter HN4 and K562 cells, and the HgS and Zote have the same effect of promoting the medicinal components of the compound medicine to enter the cells. The increment effects of HgS and zotara 48h and 72h on the entering of the two medicines into HN4 cells are equivalent, 11.26 +/-5.09% and 15.52 +/-5.23% are respectively realized in 48h, and 32.24 +/-9.20% and 33.37 +/-13.24% are respectively realized in 72h (figure 1, the effect of HgS and zotara on promoting the effective components of the seventy-flavor pearl pills to enter the HN4 cells is realized); the effect of promoting the medicine to enter the K562 cells is most obvious in 48 hours, and the increment is 53.50 +/-16.62 percent and 50.15 +/-15.93 percent respectively (figure 2, HgS and zotara promote the seventy-flavor pearl pill medicine effective components to enter the K562 cells).

The HgS can promote the medicinal components in the Renqingjue of the Tibetan medicine compound medicine to enter HN4 and K562 cells, and the promotion effect of the HgS on the medicinal components of the two medicines entering the cells is better than the effect of the Zote, as shown in figure 3 and figure 4, the increment of the Zote and the HgS on the medicinal components entering the HN4 cells is respectively 114.4 +/-42.6 percent and 133.9 +/-49.4 percent in 48 hours, and is respectively 76.9 +/-20.2 percent and 82.2 +/-19.2 percent in 72 hours. The increment of the Zuotai and the HgS for the drug effect components entering the K562 cells is respectively 25.7 +/-20.5 percent and 14.2 +/-19.1 percent at 48 hours, and the increment of the HgS is respectively 41.5 +/-9.2 percent and 56.0 +/-3.0 percent at 72 hours. Fig. 3 shows the effect of HgS and zotara on promoting entry of renqingchangjue medicinal components into HN4 cells, and fig. 4 shows the effect of HgS and zotara on promoting entry of renqingchangjue medicinal components into K562 cells. HgS and zotaro reach synergistic effect by increasing the medicine entering into the cell, and HgS can replace zotaro in the aspect of promoting the medicine to enter the cell.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

The application of HgS in preparing a medicine for enhancing the effect of a compound medicine by replacing zotara; the compound medicine comprises seventy-ingredient pearl pills and/or Renqingchang jujue.
2. Use according to claim 1, wherein the HgS has a purity of above 99%.
3. Use according to claim 1, wherein the HgS is cryogenically ground or water-in-the-air treated prior to preparation; the cryogenic grinding comprises ice bath grinding or liquid nitrogen grinding.
4. The use of claim 1, wherein HgS replaces zotare by 1/10-2 times the dose of zotare.
5. The use of claim 1, wherein the mass ratio of the compound medicament to HgS is (5-20000): 1.
6. The use according to claim 1, wherein the medicament is in a dosage form comprising a powder or granules.
7. The use according to claim 1, wherein the medicament further comprises pharmaceutically acceptable excipients, and the excipients of the granule comprise starch, milk and/or hydroxymethyl cellulose.