CN114886942B - Hemostatic composition and application thereof - Google Patents

Hemostatic composition and application thereof Download PDF

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CN114886942B
CN114886942B CN202210541479.4A CN202210541479A CN114886942B CN 114886942 B CN114886942 B CN 114886942B CN 202210541479 A CN202210541479 A CN 202210541479A CN 114886942 B CN114886942 B CN 114886942B
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cyclodextrin
dencichine
hemostatic
oil
weeping
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CN114886942A (en
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孙秋
丁瑞
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Yunnan West Grass Resources Development Co ltd
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A61K36/634—Forsythia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/738—Cyclodextrins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

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Abstract

The invention belongs to the technical field of traditional Chinese medicines, and discloses a hemostatic composition and application thereof, wherein the hemostatic composition comprises the following raw materials in percentage by mass: cyclodextrin coats 20-40% of weeping forsythia oil and 60-80% of dencichine. The invention selects the dencichine with obvious hemostatic effect as the main component, but the dencichine has neurotoxic effect, and by adding the weeping forsythiae oil wrapped by the dextrin, the neurotoxicity brought by oral administration of the dencichine can be obviously reduced, the hemostatic time can be effectively shortened, and the wound infection can be prevented; meanwhile, the addition of the weeping forsythia oil can play a synergistic effect on the hemostatic effect of the dencichine, and the use of the dencichine is reduced. The hemostatic composition can be applied to external accidental bleeding, visceral bleeding, hemorrhoids bleeding and the like of a body, and can also be added into daily care products such as washing care products like toothpaste and the like.

Description

Hemostatic composition and application thereof
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and relates to a hemostatic composition and application thereof.
Background
Blood is an important substance for human body, and if bleeding symptoms are not timely and effectively stopped, blood is consumed, so that the organism is weakened, even life is endangered, and therefore, the application of the hemostatic has important significance. Existing hemostatic agents are of a wide variety and each has advantages, but each also has its limitations: some have complex formulation, more than ten components, slow hemostatic speed and long treatment course. The traditional Chinese medicine composition for treating stasis and hemostasis has a plurality of problems of more raw material components, complex preparation process, slow effect, inaccurate curative effect and the like. For example, chinese patent CN200810102726.0 discloses a traditional Chinese medicine composition for promoting blood circulation and removing blood stasis, which is prepared from nearly 30 traditional Chinese medicinal materials such as angelica sinensis, ligusticum chuanxiong, radix salviae miltiorrhizae, polygonum multiflorum, frankincense, myrrh, radix curcumae, rhizoma atractylodis macrocephalae, pawpaw, radix achyranthis bidentatae, lapis chloriti, safflower, earthworm, cistanche, amber, poria with hostwood, emblic leafflower fruit, pangolin scales, leech, pollen typhae, peach kernel, rhizoma gastrodiae, astragalus mongholicus, pseudo-ginseng, arisaema cum bile, rhizoma acori graminei, radix codonopsis, radix puerariae and the like, and the raw material components of the composition are excessive; the preparation process of the composition is rough, and the medicine effect is not clear.
Disclosure of Invention
Aiming at the problems of multiple components, slow effect and inaccurate curative effect of the traditional hemostatic traditional Chinese medicine, the invention provides the hemostatic composition which has the effects of protecting nerves, preventing the toxic and side effects of dencichine, promoting the hemostatic effect of dencichine and shortening the hemostatic time.
A hemostatic composition comprises the following raw materials in percentage by mass: cyclodextrin coats 20-40% of weeping forsythia oil and 60-80% of dencichine.
The hemostatic traditional Chinese medicine composition has the following pharmacology components:
dencichine: the hemostatic with blood stasis removing effect can stop bleeding without retaining blood stasis, and increase platelet number; however, several studies on dencichine-induced retardation have shown that it has definite neurotoxicity.
Fructus forsythiae: sex flavor meridian tropism: bitter and slightly cold. Enter lung, heart and gallbladder meridians; has effects of clearing heat and detoxicating, relieving fever and promoting urination, resolving carbuncle and resolving hard mass, and resisting inflammation; meanwhile, has the effects of protecting brain, improving intelligence and improving learning and memory capacity.
The various raw materials used in the invention can be purchased from market, and the specification of the raw materials is pharmaceutical grade or food grade. The hemostatic traditional Chinese medicine composition disclosed by the invention is prepared from the dencichine and the weeping forsythia oil, fully utilizes the complementary superposition effect of the excellent performance characteristics of the raw material medicines and the performances of the raw material medicines, has obvious efficacy, has various functions of stopping bleeding, promoting granulation, preventing infection and the like, and can reduce the neurotoxic effect of the dencichine by the weeping forsythia oil for the first time.
Preferably, the purity of the dencichine is more than or equal to 80 percent.
Preferably, the cyclodextrin-coated weeping forsythia oil is prepared by the following method:
(1) Placing beta-cyclodextrin in a magnetic stirring pot, adding distilled water 15 times of the beta-cyclodextrin in mass, heating to dissolve the beta-cyclodextrin, then cooling to 45 ℃, and stirring at constant temperature for 40 min to obtain cyclodextrin solution;
(2) Adding weeping forsythiae oil into the cyclodextrin solution in the step (1), magnetically stirring for 60-80min, refrigerating for 15-20h at 3-5 ℃ after stirring, and drying to obtain the cyclodextrin-coated weeping forsythiae oil.
Preferably, the mass ratio of the beta-cyclodextrin to the weeping forsythia oil is 1:0.3.
The invention also aims to provide an external hemostatic drug which comprises the following raw materials in percentage by mass: cyclodextrin coats 20-40% of weeping forsythia oil and 60-80% of dencichine.
Preferably, the preparation method of the external hemostatic drug comprises the following steps: the cyclodextrin of the formula amount is coated with weeping forsythia oil and sanchinin, mixed and crushed, and sieved by a 100-120 mesh sieve, and the obtained powder mixture is the blood stopping medicine.
Compared with the prior art, the invention has the beneficial effects that:
(1) The invention selects the dencichine with obvious hemostatic effect as the main component, but the dencichine has neurotoxic effect, and by adding the weeping forsythiae oil wrapped by the dextrin, the neurotoxicity brought by the dencichine in use can be obviously reduced, the hemostatic time is effectively shortened, and the wound infection is prevented; meanwhile, the addition of the weeping forsythia oil can play a synergistic effect on the hemostatic effect of the dencichine, and the use of the dencichine is reduced.
(2) The hemostatic traditional Chinese medicine composition disclosed by the invention is simple in formula, only two raw material medicines are selected for compatibility, the excellent performance characteristics of the raw material medicines and the complementary superposition effects of the raw material medicines are fully applied, the medicinal effect is obvious, the hemostatic traditional Chinese medicine composition has a hemostatic function, and the cost is reduced; the hemostatic medicine prepared based on the composition is convenient to use, good in hemostatic effect and free from wound infection; the method for preparing the hemostatic drug by using the composition is simple to operate and is suitable for industrial production.
(3) The hemostatic composition can be applied to external accidental bleeding, visceral bleeding, hemorrhoids bleeding and the like of a body, and can also be added into daily care products such as washing care products like toothpaste and the like.
Detailed Description
The following describes the invention in more detail. The description of these embodiments is provided to assist understanding of the present invention, but is not intended to limit the present invention. In addition, the technical features of the embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.
Example 1
A hemostatic composition comprises the following raw materials in percentage by mass: cyclodextrin encapsulates weeping forsythia oil 20 g and dencichine 80g.
The cyclodextrin-coated weeping forsythia oil is prepared by the following method:
(1) Placing beta-cyclodextrin in a magnetic stirring pot, adding distilled water 15 times of the beta-cyclodextrin in mass, heating to dissolve the beta-cyclodextrin, then cooling to 45 ℃, and stirring at constant temperature for 40 min to obtain cyclodextrin solution;
(2) Adding weeping forsythiae oil into the cyclodextrin solution in the step (1), magnetically stirring for 60min, cooling at 3 ℃ for 15h after stirring, and drying to obtain the cyclodextrin-coated weeping forsythiae oil.
And (3) mixing and crushing the cyclodextrin-coated weeping forsythia oil and sanchinin according to the formula amount, sieving with a 100-mesh sieve, and sealing for later use.
Example 2
A hemostatic composition comprises the following raw materials in percentage by mass: 30g of weeping forsythia oil and 70g of dencichine are coated by cyclodextrin.
The cyclodextrin-coated weeping forsythia oil is prepared by the following method:
(1) Placing beta-cyclodextrin in a magnetic stirring pot, adding distilled water 15 times of the beta-cyclodextrin in mass, heating to dissolve the beta-cyclodextrin, then cooling to 45 ℃, and stirring at constant temperature for 40 min to obtain cyclodextrin solution;
(2) Adding weeping forsythiae oil into the cyclodextrin solution in the step (1), magnetically stirring for 80min, cooling at 4 ℃ for 20h after stirring, and drying to obtain the cyclodextrin-coated weeping forsythiae oil.
And (3) mixing and crushing the cyclodextrin-coated weeping forsythia oil and sanchinin according to the formula amount, sieving with a 100-mesh sieve, and sealing for later use.
Example 3
A hemostatic composition comprises the following raw materials in percentage by mass: cyclodextrin encapsulates oleum forsythiae 40 g and dencichine 60g.
The cyclodextrin-coated weeping forsythia oil is prepared by the following method:
(1) Placing beta-cyclodextrin in a magnetic stirring pot, adding distilled water 15 times of the beta-cyclodextrin in mass, heating to dissolve the beta-cyclodextrin, then cooling to 45 ℃, and stirring at constant temperature for 40 min to obtain cyclodextrin solution;
(2) Adding weeping forsythiae oil into the cyclodextrin solution in the step (1), magnetically stirring for 70min, cooling at 5 ℃ for 18h after stirring, and drying to obtain the cyclodextrin-coated weeping forsythiae oil.
And (3) mixing and crushing cyclodextrin coated weeping forsythia oil and sanchinin according to the formula amount, sieving with a 120-mesh sieve, and sealing for later use.
Comparative example 1
Notoginseng essence (purity 95%) powder.
Comparative example 2
Notoginseng essence (purity 95%) powder.
Experimental analysis
Test of efficacy
1.1 Experimental materials
Test animals: SPF-grade healthy adult Kunming male mice, weighing 28+ -2 g;
test sample: hemostatic compositions prepared in examples 1-3 and comparative examples 1-2.
1.2 Experimental methods
a. After the experimental mice are fed with water normally and are adapted to the environment for one week, 60 mice are randomly divided into 5 groups according to the body weight, namely an experimental group 1, an experimental group 2, an experimental group 3, a comparison group 1 and a comparison group 2;
b. after the experimental animals are adapted to the environment for one week, the animals are fasted for 24 hours;
c. taking 60 fasted mice, and 12 mice in each group; the corresponding drug solution was given by gavage of each group at 0.2. 0.2 mL/10 g, after 1 h administration, the 1.0cm tip of the mouse tail was cut off at 24-25 ℃ at room temperature, the time was counted after the blood was self-flowing out, the blood drops were sucked off with filter paper every 10 s, until no bleeding was stopped, the bleeding time was calculated, and the response of the mice after administration was observed.
1.3 experimental results
The specific results are shown in Table 1. From the data in Table 1, it can be seen that dencichine has effect of shortening bleeding time in tail-breaking mice at a certain dosage, but at the same time, different degrees of neurotoxic reactions appear in animal bodies along with different dosage amounts; in contrast, no adverse reaction was observed in mice after the sanchinin composition of the present experimental group was filled with the stomach, and the sanchinin content (calculated as pure sanchinin) was 0.1 g.kg -1 The hemostatic time is obviously shortened under the dosage of the medicine, and the medicine combination has good hemostatic effect, can reduce the dosage and can prevent the occurrence of neurotoxicity.
TABLE 1
The foregoing description of the preferred embodiments of the invention is provided to assist in understanding the principles of the embodiments of the invention; meanwhile, as for those skilled in the art, according to the present embodiment, there are various modifications in the specific embodiments and application ranges, and the present disclosure should not be construed as limiting the present invention.

Claims (3)

1. A hemostatic composition, characterized by: the material comprises the following raw materials in percentage by mass: cyclodextrin is used for coating 20% -40% of weeping forsythia oil, and 60% -80% of dencichine, the purity of dencichine is more than or equal to 80%, and the mass ratio of cyclodextrin to weeping forsythia oil is 1:0.3; wherein the cyclodextrin-coated weeping forsythia oil is prepared by the following method:
(1) Placing beta-cyclodextrin into a magnetic stirring pot, adding distilled water 15 times of the beta-cyclodextrin in mass, heating to dissolve,
then cooling to 45 ℃, and stirring at constant temperature for 40 min to obtain cyclodextrin solution;
(2) Adding weeping forsythiae oil into the cyclodextrin solution in the step (1), magnetically stirring for 60-80min, refrigerating for 15-20h at 3-5 ℃ after stirring, and drying to obtain the cyclodextrin-coated weeping forsythiae oil.
2. A hemostatic composition according to claim 1, wherein: the material comprises the following raw materials in percentage by mass: cyclodextrin encapsulates 30% of weeping forsythia oil and 70% of dencichine.
3. Use of the hemostatic composition of claim 1 in the preparation of a hemostatic medicament.
CN202210541479.4A 2022-05-19 2022-05-19 Hemostatic composition and application thereof Active CN114886942B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016109638A1 (en) * 2014-12-30 2016-07-07 Rutgers, The State University Of New Jersey Compositions and methods to prevent and repair acute kidney injury
KR20180128773A (en) * 2017-05-24 2018-12-04 휴먼코스메틱 주식회사 A composition for antioxidating, whitening and improving wrinkle comprising forsythia fruit oil or peony oil
CN114344942A (en) * 2022-01-10 2022-04-15 天水师范学院 Pretreatment method for extracting dencichine from plants

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016109638A1 (en) * 2014-12-30 2016-07-07 Rutgers, The State University Of New Jersey Compositions and methods to prevent and repair acute kidney injury
KR20180128773A (en) * 2017-05-24 2018-12-04 휴먼코스메틱 주식회사 A composition for antioxidating, whitening and improving wrinkle comprising forsythia fruit oil or peony oil
CN114344942A (en) * 2022-01-10 2022-04-15 天水师范学院 Pretreatment method for extracting dencichine from plants

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
徐冬英编著.《三七的药学与临床研究》.中国中医药出版社,2008,第13页. *
詹益兴主编.《精细化工新产品 第4集》.科学技术文献出版社,2009,第112-114页. *

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