阅读说明：本技术 一种含甲壳素的止血组合物及其气雾剂 (Hemostatic composition containing chitin and aerosol thereof ) 是由 张建广 于 2020-07-29 设计创作，主要内容包括：本发明公开一种含甲壳素的止血组合物及其气雾剂。具体地,本发明提供一种药物组合物,所述的药物组合物为乳液,所述的乳液包括：(A)水相,所述的水相包括甲壳素、氢氧化钠、碳酰胺、提取物和水,所述的提取物为菊花、车前草和月桂叶的水提取物；(B)油相,所述的油相包括棕榈油、蓖麻油和硬脂酸；和(C)乳化剂,所述的乳化剂包括辛基酚聚氧乙烯醚。本发明所述药物组合物能够有效对出血伤口处进行快速止血、促进伤口愈合和消炎,从而有效降低出血对患者造成的痛苦。(The invention discloses a hemostatic composition containing chitin and an aerosol thereof. Specifically, the invention provides a pharmaceutical composition, which is an emulsion comprising: (A) the water phase comprises chitin, sodium hydroxide, carbamide, extracts and water, wherein the extracts are water extracts of chrysanthemum, plantain and laurel leaves; (B) an oil phase comprising palm oil, castor oil, and stearic acid; and (C) an emulsifier, wherein the emulsifier comprises octyl phenol polyoxyethylene ether. The pharmaceutical composition can effectively and rapidly stop bleeding at bleeding wounds, promote wound healing and diminish inflammation, thereby effectively reducing pain of patients caused by bleeding.)

1. A pharmaceutical composition, wherein said pharmaceutical composition is an emulsion, and wherein said emulsion comprises:

(A) the water phase comprises chitin, sodium hydroxide, carbamide, extracts and water, wherein the extracts are water extracts of chrysanthemum, plantain and laurel leaves;

(B) an oil phase comprising palm oil, castor oil, and stearic acid; and

(C) the emulsifier comprises octyl phenol polyoxyethylene ether.

2. The pharmaceutical composition of claim 1, wherein the oil phase further comprises artemisinin.

3. The pharmaceutical composition of claim 1, wherein the weight ratio of chrysanthemum, plantain herb and laurel leaf is (1-5): (3-7): (0.5-4).

4. The pharmaceutical composition of claim 1, wherein the aqueous phase is present in an amount of 60-70% (w/w), based on the total weight of the composition; and/or

The content of the oil phase is 25-40% (w/w) based on the total weight of the composition.

5. The pharmaceutical composition of claim 1, wherein the formulation of the composition comprises:

prescription components Parts by weight Palm oil 100-200 Castor oil 80-160 Stearic acid 40-80 Octyl phenol polyoxyethylene ether OP-10 10-30 Extract of plant 15-35 Sodium hydroxide 2-20 Carbonamides 1-10 Chitin 10-30 Glycerol 20-40 Water (W) 500-600

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (1-5): (3-7): (0.5-4).

6. The pharmaceutical composition of claim 1, wherein the formulation of the composition comprises:

prescription components Parts by weight Optionally artemisinin 8-12 Palm oil 140-160 Castor oil 110-130 Stearic acid 55-65 Octyl phenol polyoxyethylene ether OP-10 18-22 Extract of plant 22-28 Sodium hydroxide 8-12 Carbonamides 4-6 Chitin 17-23 Glycerol 27-33 Water (W) 550-570

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

7. A process for preparing the pharmaceutical composition of claim 1, comprising the steps of:

(1) adding sodium hydroxide and carbamide with the prescription amount into water with the prescription amount of 1/3-1/5, then adding chitin with the prescription amount, fully stirring at low temperature, then adding octylphenol polyoxyethylene ether with the prescription amount, an extract, an optional wetting agent and the rest amount of water, and fully stirring at 65-75 ℃ to obtain an aqueous phase A;

(2) mixing and heating palm oil, castor oil, stearic acid and optional artemisinin according to the prescription amount to 65-75 ℃, stirring, mixing and dissolving to obtain an oily phase B;

(3) slowly injecting the oily phase B into the aqueous phase A under stirring, continuously stirring uniformly for 4-6min, homogenizing for 4-6min at 8000-.

8. An aerosol formulation comprising the pharmaceutical composition of claim 1 and a propellant comprising HFC-134A;

the dosage of the propellant is 5-15% (w/w) based on the total weight of the aerosol.

9. Use of a pharmaceutical composition according to claim 1 for the preparation of a pharmaceutical preparation for hemostasis, wound healing promotion and/or anti-inflammation.

10. The use of claim 9, wherein the wound comprises a skin wound.

Technical Field

The invention relates to the field of medicine, in particular to a hemostatic composition containing chitin and an aerosol thereof.

Background

The rapid hemostasis of the wound is a big problem, especially in the field activity, often can't arrive clinic or hospital in time after the wound bleeds and carry out effective treatment, lead to hemostasis speed slow, and blood loss is many, and often takes place a large amount of inflammatory factor aggregations and lead to the inflammation to take place in the wound, and the pus appears in serious person, if can't in time treat and can cause very big misery.

However, the existing rapid hemostatic materials often have the disadvantages of slow speed of hemostasis and wound healing promotion, incapability of effectively diminishing inflammation and suppuration, high price and the like, so that the hemostasis, healing promotion and inflammation diminishing cannot be rapidly realized, and the pain is caused to patients.

Therefore, there is a need in the art to develop a hemostatic material with high hemostatic and healing promoting speed and good anti-inflammatory effect, so as to effectively reduce pain caused by bleeding.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition with high speed of hemostasis and healing promotion and good anti-inflammatory effect, thereby effectively reducing pain caused by bleeding.

In a first aspect of the present invention, there is provided a pharmaceutical composition, wherein the pharmaceutical composition is an emulsion, and the emulsion comprises:

(A) the water phase comprises chitin, sodium hydroxide, carbamide, extracts and water, wherein the extracts are water extracts of chrysanthemum, plantain and laurel leaves;

(B) an oil phase comprising palm oil, castor oil, and stearic acid;

(C) the emulsifier comprises octyl phenol polyoxyethylene ether.

Preferably, the extract is water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf.

Preferably, the composition is an emulsion.

Preferably, the aqueous phase further comprises a wetting agent.

Preferably, the humectant comprises one or more of glycerol, propylene glycol and polyethylene glycol.

Preferably, the emulsion is an oil-in-water emulsion.

Preferably, the water is distilled water.

Preferably, the extract is a dry extract.

Preferably, the extract is a dry extract.

Preferably, the extract is a water-soluble dry extract.

Preferably, the polyoxyethylene octylphenol ether comprises polyoxyethylene octylphenol ether OP-10.

Preferably, the weight ratio of the chrysanthemum to the plantain to the laurel leaf is (1-5): (3-7): (0.5-4), preferably (2-4): (4-6): (1-3).

Preferably, the weight ratio of the chrysanthemum to the plantain is (1-5): (3-7), preferably (2-4): (4-6).

Preferably, the weight ratio of the chrysanthemum to the laurel leaf is (1-5): (0.5-4), preferably (2-4): (1-3).

Preferably, the chitin is 10-30 parts by weight, preferably 15-25 parts by weight, preferably 17-23 parts by weight.

Preferably, the sodium hydroxide is present in an amount of 2 to 20 parts by weight, preferably 5 to 15 parts by weight, more preferably 8 to 12 parts by weight.

Preferably, the weight part of the carbamide is 1-10 parts, preferably 2-8 parts, preferably 4-6 parts.

Preferably, the weight part of the extract is 15-35 parts, preferably 20-30 parts, more preferably 22-28 parts.

Preferably, the weight part of the water is 500-600 parts, preferably 540-580 parts, and preferably 550-570 parts.

Preferably, the weight portion of the palm oil is 200 portions, preferably 120 portions, 180 portions, preferably 140 portions, 160 portions.

Preferably, the weight portion of the castor oil is 80-160, preferably 100-140, preferably 110-130.

Preferably, the stearic acid is present in an amount of 40 to 80 parts by weight, preferably 50 to 70 parts by weight, preferably 55 to 65 parts by weight.

Preferably, the humectant (e.g., glycerin) is present in an amount of 20 to 40 parts by weight, preferably 25 to 35 parts by weight, more preferably 27 to 33 parts by weight.

Preferably, the weight part of the octylphenol polyoxyethylene ether is 10 to 30 parts, preferably 15 to 25 parts, and more preferably 18 to 22 parts.

Preferably, the unit of parts by weight is grams (g).

Preferably, the oil phase further comprises artemisinin.

Preferably, the artemisinin is 5-15 parts by weight, preferably 8-12 parts by weight.

Preferably, the aqueous phase is present in an amount of 60-70% (w/w), preferably 63-70% (w/w), based on the total weight of the composition.

Preferably, the oil phase is present in an amount of 25-40% (w/w), preferably 30-35% (w/w), based on the total weight of the composition.

Preferably, the emulsifier is present in an amount of 1-8% (w/w), preferably 1-5% (w/w), based on the total weight of the composition.

Preferably, the water phase, the oil phase and the emulsifier are used in a total amount of 100% (w/w) based on the total weight of the composition.

Preferably, the extract is prepared by the following method:

mixing flos Chrysanthemi, herba plantaginis and laurel leaf, pulverizing, extracting with water, filtering, concentrating the filtrate, and drying to obtain the extract.

Preferably, the extract is prepared by the following method:

mixing flos Chrysanthemi, herba plantaginis and laurel leaf, pulverizing, adding 4-6 times of water, extracting at 65-75 deg.C for 8-14 hr, filtering, concentrating the filtrate, and drying to obtain the extract.

Preferably, the drying is concentration drying under reduced pressure.

Preferably, the prescription of the pharmaceutical composition comprises:

the extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (1-5): (3-7): (0.5-4).

Preferably, the prescription of the pharmaceutical composition comprises:

prescription components	Parts by weight
		Palm oil	120-180
Castor oil	100-140
		Stearic acid	50-70
Octyl phenolPolyoxyethylene ether OP-10	15-25
		Extract of plant	20-30
Sodium hydroxide	5-15
		Carbonamides	2-8
Chitin	15-25
		Glycerol	25-35
Water (W)	540-580

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

Preferably, the prescription of the pharmaceutical composition comprises:

prescription components	Parts by weight
		Palm oil	140-160
Castor oil	110-130
		Stearic acid	55-65
Octyl phenol polyoxyethylene ether OP-10	18-22
		Extract of plant	22-28
Sodium hydroxide	8-12
		Carbonamides	4-6
Chitin	17-23
		Glycerol	27-33
Water (W)	550-570

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

Preferably, the prescription of the pharmaceutical composition comprises:

prescription components	Parts by weight
		Optionally artemisinin	5-15
Palm oil	120-180
		Castor oil	100-140
Stearic acid	50-70
		Octyl phenol polyoxyethylene ether OP-10	15-25
Extract of plant	20-30
		Sodium hydroxide	5-15
Carbonamides	2-8
		Chitin	15-25
Glycerol	25-35
		Water (W)	540-580

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

Preferably, the prescription of the pharmaceutical composition comprises:

prescription components	Parts by weight
		Optionally artemisinin	8-12
Palm oil	140-160
		Castor oil	110-130
Stearic acid	55-65
		Octyl phenol polyoxyethylene ether OP-10	18-22
Extract of plant	22-28
		Sodium hydroxide	8-12
Carbonamides	4-6
		Chitin	17-23
Glycerol	27-33
		Water (W)	550-570

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

Preferably, the emulsion has an average particle size of 60-90nm, preferably 60-90 nm.

Preferably, the composition is in the form of an emulsion.

Preferably, the composition is in the form of an external preparation or an aerosol.

In a second aspect of the invention, there is provided a process for the preparation of a pharmaceutical composition according to the first aspect of the invention, said process comprising the steps of:

(1) adding sodium hydroxide and carbamide with the prescription amount into water with the prescription amount of 1/3-1/5, then adding chitin with the prescription amount, fully stirring at low temperature, then adding octylphenol polyoxyethylene ether with the prescription amount, an extract, an optional wetting agent and the rest amount of water, and fully stirring at 65-75 ℃ to obtain an aqueous phase A;

(2) mixing and heating palm oil, castor oil, stearic acid and optional artemisinin according to the prescription amount to 65-75 ℃, stirring, mixing and dissolving to obtain an oily phase B;

(3) slowly injecting the oily phase B into the aqueous phase A under stirring, continuously stirring uniformly for 4-6min, homogenizing for 4-6min at 8000-.

In a third aspect of the invention, there is provided an aerosol formulation comprising a pharmaceutical composition according to the first aspect of the invention and a propellant.

Preferably, the propellant comprises HFC-134A.

Preferably, the propellant is used in an amount of 5-15% (w/w), preferably 8-12% (w/w).

Preferably, the aerosol further comprises an aerosol canister, the composition and propellant being located in the aerosol canister.

In a fourth aspect of the invention, there is provided a method of preparing an aerosol formulation as described in the third aspect of the invention, said method comprising the steps of:

the pharmaceutical composition according to the first aspect of the present invention is filled into an aerosol canister, a valve is added, a propellant is filled after the valve is closed, and then an aerosol is prepared after a canister cap is installed.

In a fifth aspect of the present invention, there is provided a use of the pharmaceutical composition according to the first aspect of the present invention for preparing a pharmaceutical preparation for hemostasis, wound healing promotion and/or anti-inflammation.

Preferably, the wound comprises a skin wound.

Preferably, the wound comprises a skin wound that is below the dermis.

Preferably, the inflammation comprises inflammation at a wound.

Preferably, the anti-inflammatory is by reducing inflammatory factors.

Preferably, the inflammatory factors include IL-1 β, IL-6 and/or TNF- α.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments.

Detailed Description

The invention has developed a pharmaceutical composition, the said composition is the latex emulsion, the said latex emulsion includes aqueous phase, oil phase and emulsifier, the said aqueous phase includes chitin, sodium hydroxide, carbamide, extract and water, the said extract is the aqueous extract of flos Chrysanthemi, herba plantaginis and laurel leaf; the oil phase comprises palm oil, castor oil and stearic acid, and the emulsifier comprises octyl phenol polyoxyethylene ether. Experimental research shows that the emulsion composition can effectively and rapidly stop bleeding at bleeding wounds, promote wound healing and diminish inflammation, and accordingly pain of patients caused by bleeding is effectively reduced.

Term(s) for

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, the terms "comprising," including, "and" containing "are used interchangeably and include not only open-ended definitions, but also semi-closed and closed-ended definitions, and include" consisting of … …, "" consisting essentially of … ….

As used herein, Chrysanthemum is a dried capitula of the Compositae plant Chrysanthemum morifolium Ramat.

As used herein, plantain is a dried or fresh whole plant of the Plantago asiatica l.

As used herein, laurel leaf is the leaf of Laurus nobilis l.

Pharmaceutical composition and preparation method thereof

The invention provides a pharmaceutical composition capable of rapidly stopping bleeding, promoting wound healing and diminishing inflammation at a bleeding wound, typically an emulsion, comprising:

(A) the water phase comprises chitin, sodium hydroxide, carbamide, extracts and water, wherein the extracts are water extracts of chrysanthemum, plantain and laurel leaves;

(B) an oil phase comprising palm oil, castor oil, and stearic acid; and

(C) the emulsifier comprises octyl phenol polyoxyethylene ether.

In a preferred embodiment of the present invention, the aqueous phase further comprises a wetting agent. Typically, the humectant includes, but is not limited to, one or more of glycerin, propylene glycol, and polyethylene glycol.

In another preferred mode of the invention, in the extract in the aqueous phase, the weight ratio of the chrysanthemum, the plantain and the laurel leaf is (1-5): (3-7): (0.5-4), preferably (2-4): (4-6): (1-3).

Typically, the formulation of the composition comprises:

prescription components	Parts by weight
		Palm oil	100-200
Castor oil	80-160
		Stearic acid	40-80
Octyl phenol polyoxyethylene ether OP-10	10-30
		Extract of plant	15-35
Sodium hydroxide	2-20
		Carbonamides	1-10
Chitin	10-30
		Glycerol	20-40
Water (W)	500-600

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (1-5): (3-7): (0.5-4).

Preferably, the formulation of said composition comprises:

the extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

Preferably, the formulation of said composition comprises:

prescription components	Parts by weight
		Palm oil	140-160
Castor oil	110-130
		Stearic acid	55-65
Octyl phenol polyoxyethylene ether OP-10	18-22
		Extract of plant	22-28
Sodium hydroxide	8-12
		Carbonamides	4-6
Chitin	17-23
		Glycerol	27-33
Water (W)	550-570

The extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

Preferably, the prescription of the pharmaceutical composition comprises:

the extract is a water extract of mixed medicinal materials of chrysanthemum, plantain herb and laurel leaf, wherein the weight ratio of the chrysanthemum to the plantain herb to the laurel leaf is (2-4): (4-6): (1-3).

The present invention also provides a process for preparing the pharmaceutical composition of the present invention, said process comprising the steps of:

(1) adding sodium hydroxide and carbamide with the prescription amount into water with the prescription amount of 1/3-1/5, then adding chitin with the prescription amount, fully stirring at low temperature, then adding octylphenol polyoxyethylene ether with the prescription amount, an extract, an optional wetting agent and the rest amount of water, and fully stirring at 65-75 ℃ to obtain an aqueous phase A;

(2) mixing and heating palm oil, castor oil and stearic acid in a formula amount to 65-75 ℃, stirring, mixing and dissolving to obtain an oily phase B;

(3) slowly injecting the oily phase B into the aqueous phase A under stirring, continuously stirring uniformly for 4-6min, homogenizing for 4-6min at 8000-.

Aerosol and preparation method thereof

The present invention also provides an aerosol comprising a pharmaceutical composition according to the present invention and a propellant.

Preferably, the propellant comprises HFC-134A.

Preferably, the aerosol further comprises an aerosol canister, the composition and propellant being located in the aerosol canister.

The present invention also provides a method of preparing an aerosol formulation according to the invention, the method comprising the steps of:

the pharmaceutical composition is filled into an aerosol can, a valve is added, the propellant is filled after the opening of the valve is sealed, and the aerosol is prepared after a can cover is installed.

Use of

The invention also provides an application of the pharmaceutical composition provided by the invention in preparing a pharmaceutical preparation, wherein the pharmaceutical preparation is used for stopping bleeding, promoting wound healing and/or resisting inflammation.

In a preferred embodiment, the wound comprises a skin wound.

In another preferred embodiment, the inflammation comprises inflammation at a wound.

Preferably, the anti-inflammatory is by reducing inflammatory factors.

Preferably, the inflammatory factors include, but are not limited to, IL-1 β, IL-6 and/or TNF- α.

The main technical effects of the invention comprise:

1. the invention develops an emulsion composition which can effectively and rapidly stop bleeding at bleeding wounds, promote wound healing and diminish inflammation, thereby effectively reducing pain of patients caused by bleeding.

2. The emulsion composition can be prepared into aerosol, and the emulsion composition can be conveniently, simply and quickly sprayed to wounds in a spraying mode, so that the pain of a patient caused by bleeding is quickly reduced, and the aerosol is convenient to carry.

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention.