阅读说明：本技术 银杏萃取物用于制备治疗局部缺血的医药组合物及用途 (Ginkgo extract used for preparing pharmaceutical composition for treating ischemia and application thereof ) 是由 穆淑琪 于 2020-10-29 设计创作，主要内容包括：本发明的名称为银杏萃取物用于制备治疗局部缺血的医药组合物及用途。本发明公开了一种治疗局部缺血的医药组合物,其是用于罹患局部缺血的患者。医药组合物包括银杏萃取物(ginkgo extraction)以及医药上可接受的载体,其中医药组合物的剂型为凝胶、经皮贴剂、霜剂或膏剂。患者是新生儿、婴儿或幼儿。本发明另外公开了一种银杏萃取物用于制备治疗局部缺血的医药组合物的用途。利用本发明的用途及医药组合物,可用于治疗局部缺血。(The invention relates to a ginkgo biloba extract for preparing a medicinal composition for treating ischemia and application thereof. The invention discloses a pharmaceutical composition for treating ischemia, which is used for patients suffering from ischemia. The pharmaceutical composition comprises ginkgo biloba extract (ginkgo extract) and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is in the form of gel, transdermal patch, cream or ointment. The patient is a neonate, an infant or a young child. The invention also discloses application of the ginkgo extract in preparing a medicinal composition for treating ischemia. The application and the medical composition can be used for treating ischemia.)

1. A pharmaceutical composition for treating ischemia, which is used for a patient suffering from ischemia, wherein the pharmaceutical composition comprises ginkgo biloba extract (ginkgo extract) and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is in the form of a gel, a transdermal patch, a cream or an ointment, and the patient is a newborn, an infant or a young child.

2. The pharmaceutical composition of claim 1, wherein the ginkgo extract is extracted from ginkgo biloba leaves and comprises 20% or more flavonoid glycosides (flavanolides) and 5% or more ginkgolides (ginkgolides).

3. The pharmaceutical composition of claim 1, wherein the dosage of the ginkgo extract is between 0.01 mg/ml and 5 mg/ml.

4. The pharmaceutical composition of claim 1, wherein the dosage of the ginkgo extract is between 0.01 mg/cm and 5 mg/cm.

5. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is mineral oil, propylene glycol, polyoxypropylene, emulsifying wax, glycerin, polyethylene glycol, fatty alcohol, fatty ether, fatty acid ester, vegetable oil, silicone oil, petrolatum, lanolin, beeswax, hyaluronic acid, polyacrylic acid, polyvinylpyrrolidone, gelatin, dextrin, polysaccharides, polyacrylamide, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl methylcellulose, or carboxypropyl methylcellulose.

6. Use of a ginkgo extract for the preparation of a pharmaceutical composition for the treatment of ischemia, said pharmaceutical composition being for use in a patient suffering from ischemia, wherein said pharmaceutical composition comprises a ginkgo extract and a pharmaceutically acceptable carrier, wherein said pharmaceutical composition is in the form of a gel, a transdermal patch, a cream or an ointment, and said patient is a neonate, an infant or a young child.

7. The use of claim 6, wherein the ginkgo extract is extracted from ginkgo biloba leaves and comprises more than 20% flavonoid glycosides and more than 5% bilobalide.

8. The use according to claim 6, wherein the dosage of said ginkgo extract is between 0.01 mg/ml and 5 mg/ml.

9. The use of claim 6, wherein the dose of the ginkgo extract is between 0.01 mg/cm and 5 mg/cm.

10. The use according to claim 6, wherein the pharmaceutically acceptable carrier is mineral oil, propylene glycol, polyoxypropylene, emulsifying wax, glycerol, polyethylene glycol, fatty alcohol, fatty ether, fatty acid ester, vegetable oil, silicone oil, petrolatum, lanolin, beeswax, hyaluronic acid, polyacrylic acid, polyvinylpyrrolidone, gelatin, dextrin, polysaccharides, polyacrylamide, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl methylcellulose or carboxypropyl methylcellulose.

Technical Field

The invention relates to a pharmaceutical composition for treating ischemia and application thereof in preparing the pharmaceutical composition.

Background

Ischemia refers to a decrease in blood content in an organ or tissue, which may be a local manifestation of systemic anemia, or a result of a local blood circulation disorder. Depending on the location of ischemia, there may be classified as limb ischemia or organ ischemia, such as brain ischemia (ischemic stroke), heart ischemia (ischemic heart disease), etc. In recent years, the incidence of peripheral arterial occlusive disease is increased due to aging of population, smoking, change of eating habits and increase of the proportion of mouths of diabetics, and the incidence of limb ischemia is increased, and the prevalence rate can even reach 11%. In addition to peripheral arterial occlusive disease, limb ischemia may also occur as a result of raynaud's phenomenon, buerger's disease, vasospasm, compression, and the like.

Limb ischemia may also occur in newborns, especially premature infants. The cause of this disease is different from that of adults and may be caused by hypoevolutism of blood vessels, anoxia, anemia, etc. However, ischemia of the extremities, whether adult or neonatal, can cause numbness, pain or coldness of the extremities, and as the ischemic time increases, it is more likely to cause purplish, blackened extremities, and even ulceration and necrosis of the tissues.

Traditionally, ischemia has been treated mainly by oral medication, however, orally administered medication acts not only on the site of ischemia but also on the whole body. Therefore, systemic or systemic side effects may be generated, and the action speed and efficacy of the drug may be easily influenced by organs (such as liver, kidney, etc.) that metabolize the drug.

Therefore, there is still a need for a pharmaceutical composition for treating ischemia and its preparation method, which can directly act on the ischemic tissue to promote blood circulation, so as to avoid numbness, pain, even purplish, blackening, ulceration or necrosis of the ischemic tissue, thereby achieving the efficacy of treating ischemia, and further avoiding the side effects caused by the action of the drug on other tissues.

Disclosure of Invention

In view of the above problems, it is an object of the present invention to provide a pharmaceutical composition for treating ischemia, which can directly act on ischemic tissue to promote blood circulation, so as to prevent numbness, pain, cold, purple, blackening, ulceration and necrosis of the ischemic tissue, thereby achieving the efficacy of treating ischemia, and simultaneously avoiding side effects caused by drug action on other tissues, and a preparation method thereof.

In order to achieve the above objects, the present invention provides a pharmaceutical composition for treating ischemia, which is used for a patient suffering from ischemia, the pharmaceutical composition comprises a ginkgo extract and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is in the form of a gel, a transdermal patch, a cream or an ointment. The patient is a neonate, an infant or a young child.

In order to achieve the above objects, the present invention further provides a use of a ginkgo extract for preparing a pharmaceutical composition for treating ischemia, the pharmaceutical composition being for a patient suffering from ischemia, the pharmaceutical composition comprising the ginkgo extract and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is in the form of a gel, a transdermal patch, a cream or an ointment. The patient is a neonate, an infant or a young child.

In one embodiment, the ginkgo extract is extracted from ginkgo biloba leaves and comprises more than 20% flavonoid glycosides (flavanglycosides) and more than 5% ginkgolides (ginkgolides).

In one embodiment, the dosage of ginkgo extract is between 0.01 mg/ml and 5 mg/ml.

In one embodiment, the dosage of ginkgo extract is between 0.01 mg/cm and 5 mg/cm.

In one embodiment, the pharmaceutically acceptable carrier is mineral oil, propylene glycol, polyoxypropylene, emulsifying wax, glycerin, polyethylene glycol, fatty alcohol, fatty ether, fatty acid ester, vegetable oil, silicone oil, petrolatum, lanolin, beeswax, hyaluronic acid, polyacrylic acid, polyvinylpyrrolidone, gelatin, dextrin, polysaccharides, polyacrylamide, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl methylcellulose, or carboxypropyl methylcellulose.

In light of the above, the present invention has the following effects: by providing a pharmaceutical composition for treating ischemia and its preparation method, the composition can directly act on ischemic tissues to promote blood circulation of the local tissues, so as to avoid numbness, pain, even purplish, blackened, ulcerated or necrotic tissues caused by ischemia, further achieve the effect of treating ischemia, and further avoid side effects caused by drug action on other tissues.

Detailed Description

Preferred embodiments and experimental examples of the pharmaceutical composition for treating ischemia according to the present invention and the preparation use thereof will be described below with reference to the associated tables, in which like elements will be described with like reference numerals.

The medicinal composition and the preparation application thereof can directly act on ischemic tissues to promote the blood circulation of the local tissues so as to avoid numbness, pain, even purplish, blackened, ulcerated or necrotic tissues caused by ischemia of the local tissues, further achieve the effect of treating the ischemia and further avoid side effects caused by the action of medicaments on other tissues.

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. Although any methods and materials similar or equivalent to those described herein can be used in the test experiments of the present invention, the preferred materials and methods are described herein. In describing and claiming the present invention, the following terminology will be used. It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

The term "ischemia" refers to a decrease in blood content in an organ or tissue, which may be a local manifestation of systemic anemia, or a result of a local blood circulation disorder. Depending on the location of ischemia, there may be classified as limb ischemia or organ ischemia, such as brain ischemia (ischemic stroke), heart ischemia (ischemic heart disease), etc. Limb ischemia may be caused by peripheral arterial occlusive disease, Raynaud's phenomenon, Burger's disease, vasospasm, compression, vascular hypoplasia, hypoxia, anemia, and the like. Ischemia of the limbs may cause numbness, pain or cold sensation at the extremities of the limbs, and with the increase of the ischemic time, the limbs may become purple, black, and even the tissues may be ulcerated and necrotized.

The term "ginkgo extract" refers to an extract obtained by extracting ginkgo biloba leaves, and includes flavonoid glycosides (flavanglycosides) and ginkgolides (ginkgolides) as active ingredients.

The term "extraction" refers to the process of separating out specific components of a mixture by utilizing the different solubilities of the different components in the mixture in a solvent. Extraction can be divided into two modes, liquid-liquid extraction and solid-liquid extraction, which are modes of separating specific components from liquid mixtures and solid mixtures, respectively.

The term "flavonoid glycosides" also known as "flavonoids" refers to a component of ginkgo biloba extract, and it is currently indicated that flavonoid glycosides have antioxidant and free radical scavenging effects.

The term "ginkgolides" refers to a component of an extract of ginkgo biloba leaves, and it is currently studied to indicate that ginkgolides are antagonists of platelet-activating factors (PAFs), which promote platelet activation and aggregation. In addition, bilobalide is also used for treating cerebrovascular diseases and migraine.

As used herein, "disease" in the health status of an individual means that the individual cannot maintain homeostasis (homeostasis), and if the disease is not improved, the health of the individual continues to deteriorate.

As used herein, the terms "treat", "treating" and "treatment" refer to reducing the frequency or severity of symptoms of a disease or disorder experienced by an individual by administering an agent or pharmaceutical composition to the individual.

As used herein, the term "pharmaceutically acceptable" refers to a material, such as a carrier or diluent, that is a ginkgo extract, or a salt, solvate, hydrate, prodrug, enantiomer, non-enantiomer, or geometric isomer thereof, useful in the present invention, which retains its biological activity or properties and is relatively non-toxic. I.e., the material can be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the ingredients contained in the composition.

As used herein, "pharmaceutically acceptable carrier" includes salts, materials, compositions or vehicles, such as fillers, diluents, excipients or encapsulating materials, which allow the ginkgo extract of the present invention to be applied to the body surface of a subject and allow the ginkgo extract to perform its intended function. Each salt or carrier must be compatible with the other ingredients of the formulation (including the ginkgo extract useful in the present invention) and not deleterious to the subject. Examples of materials that can be used as a support include: sugars such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered gum tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; a diluent; granulating; a lubricant; an adhesive; a disintegrating agent; a wetting agent; an emulsifier; a colorant; a release agent; a coating agent; a fragrance; a preservative; an antioxidant; a plasticizer; a gelling agent; a thickener; a hardening agent; a setting agent; a surfactant; a humectant; a carrier; a stabilizer; and other non-toxic compatible materials used in the formulation, or any combination thereof.

The pharmaceutical compositions of the methods of the present invention are suitable for topical or transdermal administration routes. Suitable pharmaceutical compositions are in the form of, for example, but not limited to, gels, emulsions, transdermal patches, creams, ointments (pastes).

Formulations suitable for topical administration include, but are not limited to, liquid or semi-liquid formulations such as liniments, lotions, oil-in-water or water-in-oil emulsions such as creams, ointments or ointments. Although the concentration of the active ingredient may be as high as the limit of solubility of the active ingredient in the solvent, the topically applied formulation may, for example, comprise from about 1% to about 10% (w/w) of the active ingredient. Formulations for topical administration may further comprise one or more additional ingredients as described herein.

The carrier in the gels, emulsions, transdermal patches, creams, ointments of pharmaceutical compositions for topical or transdermal administration may be, for example, but not limited to, mineral oil, propylene glycol, polyoxypropylene, emulsifying wax, glycerol, polyethylene glycol, fatty alcohols, fatty ethers, fatty acid esters, vegetable oils, silicone oils, petrolatum, lanolin, beeswax, hyaluronic acid, polyacrylic acid, polyvinyl pyrrolidone, gelatin, dextrin, polysaccharides, polyacrylamide, polyvinyl alcohol, polyvinyl acetate, hydroxypropylmethylcellulose or carboxypropylmethylcellulose.

The topically applied pharmaceutical compositions can optionally be combined with other ingredients such as adjuvants, antioxidants, chelating agents, surfactants, foaming agents, wetting agents, emulsifiers, tackifiers, buffers, preservatives, and the like. In other embodiments, a penetration or penetration enhancer is included in the composition and is effective to improve transdermal penetration of the active ingredient into and through the stratum corneum relative to compositions lacking the penetration enhancer. Various penetration enhancers are known to those skilled in the art, including oleic acid, oleyl alcohol, ethoxydiglycol, laurocapram, alkenyl carboxylic acids, dimethyl sulfoxide, polar lipids, or N-methyl-2-pyrrolidone. In another embodiment, the composition may further comprise a solubilizing agent that functions to increase the degree of disruption of the stratum corneum structure, thereby resulting in improved transport across the stratum corneum. Various solubilizers known to the person skilled in the art are, for example, isopropanol, propylene glycol or sodium xylene sulfonate.

The formulations of the pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the pharmacological and pharmaceutical arts. In general, such a preparation method comprises the following steps: combining the active ingredient with a carrier or one or more other auxiliary ingredients and then, if desired or feasible, forming or packaging the product into the intended unit dose or units of multiple doses.

As used herein, "patient," "individual," and "subject" are used interchangeably and refer to a human or non-human mammal. Non-human mammals include, for example, domestic animals and pets, such as ovine, bovine, porcine, canine, feline, and murine mammals. Preferably, the patient is a human.

The term "neonate" refers to a human within 28 days of birth. The term "infant" refers to a human between 28 days after birth and 1 year of age. The term "young child" refers to a human between the ages of 1 and 3 years. The term "preterm infant" particularly refers to a newborn infant born at 20 weeks, but less than 37 weeks of gestation.

The "dose" used in the present specification means a dose of the ginkgo extract which can promote blood circulation. In the gel, cream or ointment of the present invention, the dosage of the ginkgo extract is between 0.01 mg/ml and 5 mg/ml. Preferably, the dosage of the ginkgo extract is between 0.05 mg/ml and 3 mg/ml. Preferably, the dosage of the ginkgo extract is between 0.08 mg/ml and 2 mg/ml. In the transdermal patch of the present invention, the dosage of the ginkgo biloba extract is between 0.01 mg/cm and 5 mg/cm. Preferably, the dosage of ginkgo extract is between 0.05 mg/cm and 3 mg/cm. Preferably, the dosage of ginkgo extract is between 0.08 mg/cm and 2 mg/cm.

The range is as follows: throughout this disclosure, various embodiments of the present invention may be presented in a range format. It is to be understood that the description in range format is merely for convenience and brevity and should not be construed as limiting the scope of the claims which follow. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, a description of a range from 1 to 6 should be considered to have certain disclosed sub-ranges, such as from 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as single and fractional numbers within that range, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. The foregoing rules apply regardless of the span of the range.

The pharmaceutical composition for treating ischemia according to the present invention is used for patients suffering from ischemia, and comprises ginkgo biloba extract and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is in the form of gel, transdermal patch, cream or ointment. In this embodiment, a certain amount of ginkgo biloba extract may be extracted or weighed and added with a pharmaceutically acceptable carrier to prepare a pharmaceutical composition, which is then applied to the ischemic site of a patient to achieve the effect of promoting blood circulation in the site, and further used for treating ischemia.

In addition, the pharmaceutical composition of the present invention includes a dosage form of gel, transdermal patch, cream or ointment. In this embodiment, when the pharmaceutical composition is in the form of a gel, cream or ointment, the dosage of the ginkgo extract is between 0.01 mg/ml and 5 mg/ml, and preferably, the dosage of the ginkgo extract is between 0.05 mg/ml and 3 mg/ml. Preferably, the dosage of the ginkgo extract is between 0.08 mg/ml and 2 mg/ml. In this embodiment, when the pharmaceutical composition is in the form of a transdermal patch, the ginkgo biloba extract is administered in an amount of 0.01 mg/cm to 5 mg/cm, preferably 0.05 mg/cm to 3 mg/cm. Preferably, the dosage of ginkgo extract is between 0.08 mg/cm and 2 mg/cm. Of course, the dosage of the ginkgo extract may be any value or range encompassed between any two values within the aforementioned ranges, and may vary depending upon the carrier employed in its treatment, the route of administration, or the individual in need thereof and its physiological condition.

In this embodiment, the ginkgo extract is extracted from ginkgo biloba leaves, and includes 20% or more of flavonoid glycosides (flavanglycosides) and 5% or more of ginkgolides (ginkgolides). Preferably, the ginkgo extract comprises more than 24% flavonoid glycoside and more than 6% bilobalide.

In this embodiment, the pharmaceutically acceptable carrier is mineral oil, propylene glycol, polyoxypropylene, emulsifying wax, glycerin, polyethylene glycol, fatty alcohol, fatty ether, fatty acid ester, vegetable oil, silicone oil, vaseline, lanolin, beeswax, hyaluronic acid, polyacrylic acid, polyvinylpyrrolidone, gelatin, dextrin, polysaccharide, polyacrylamide, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl methylcellulose, or carboxypropyl methylcellulose. Preferably, the pharmaceutically acceptable carrier is petrolatum.

In this embodiment, the ischemia is limb ischemia, also referred to as limb ischemia or terminal ischemia, such as, but not limited to, chronic limb ischemia or acute limb ischemia.

In this embodiment, the patient is a neonate, an infant or a young child. Preferably, the patient is a premature infant of the newborn.

The invention also provides application of the ginkgo extract in preparing a medicinal composition for treating ischemia. In addition, the present invention provides a method for treating ischemia, comprising administering a pharmaceutical composition comprising a ginkgo extract and a pharmaceutically acceptable carrier to an affected part of a patient suffering from ischemia, the pharmaceutical composition being in the form of a gel, a transdermal patch, a cream or an ointment, the ischemia being limb ischemia, and the patient being a premature infant. However, the dosage, carrier type and other properties of the pharmaceutical composition are substantially the same as those of the pharmaceutical composition described above, and reference is made to the above description, which is not repeated herein.

In summary, according to the pharmaceutical composition and the preparation and use thereof of the present invention, the composition can directly act on the ischemic tissue to promote the blood circulation of the local tissue, so as to avoid numbness, pain, even purplish, blackened, ulcerated or necrotic tissue caused by ischemia, further achieve the efficacy of treating ischemia, and further avoid side effects caused by the action of the drug on other tissues.

The following experimental examples are provided to illustrate the use and pharmaceutical composition of the present invention, which provide significant efficacy in improving the treatment of limb ischemia.

The first experimental example: preparing the pharmaceutical composition.

A ginkgo extract (trade name: ginkgo biloba extract tablet, product name: ginkgo biloba membrane tablet, product of the pharmaceutical industry gmbh) in an amount of 0.08 mg/ml to 2 mg/ml was mixed with 1 ml of a Sterile gel (patient lubricant (Sterile), CEYOTEKPatient solvent (sterle), science and technology limited), to prepare a pharmaceutical composition containing the ginkgo extract in an amount of 0.08 mg/ml to 2 mg/ml for the subsequent experiments of experimental example two.

Experiment example two: the results of studies on ginkgo biloba extracts to improve the symptoms of acroischemia in premature infants.

The participating patients

Patients were preterm patients treated in 2018 from the memorial hospital of seiko wu-fire lion, seiko, a shin-sieu medical treasury, taiwan, who suffered from acro-ischemia. The preterm patients who performed the experiment were signed by their parents or legal agents with written informed consent approved by the Institutional Review Board (IRB).

Table 1: patient status and treatment information

Methods of treatment using the pharmaceutical compositions of the invention

The pharmaceutical composition prepared in experimental example one was applied to ischemic sites (affected parts) of patients 1, 2 and 3. The thickness of the application is about 1mm, and the application area varies according to the area of the affected part, and the affected part needs to be completely covered. After the application, a layer of gauze is covered and warm application is carried out for 30 minutes, so that the medicinal composition is absorbed by the affected part. The gauze was then removed and the pharmaceutical composition applied, covered with a new layer of gauze and left to stand for 30 minutes (no warm compress), a course of treatment. The above treatment course is repeated: applying the medicinal composition, covering with a layer of gauze, warm applying for 30 min, removing gauze, applying the medicinal composition, covering with a layer of new gauze, standing for 30 min (warm applying), recording until ischemia of affected part is improved, and continuing treatment until completely cured.

Please refer to table 1 for explaining the treatment status of patient 1. As shown in table 1, patient 1 developed ischemic symptoms at postnatal day 2, and improvement in symptoms was observed after 3 hours of treatment with the pharmaceutical composition of the present invention (3 hours after treatment, i.e., 3 courses of treatment). In addition, patient 1 had complete recovery of ischemic symptoms for 4 hours (4 hours after treatment, i.e., 4 courses of treatment).

Please refer to table 1 again for explaining the treatment status of patient 2. As shown in table 1, patient 2 developed ischemic symptoms at postnatal day 2, and improvement in symptoms was observed 3.2 hours after treatment with the pharmaceutical composition of the present invention (3 hours after treatment, i.e., 3 courses of treatment). In addition, the time for complete healing of ischemic symptoms in patient 2 was 4 hours (4 hours after treatment, i.e., 4 courses of treatment).

Please refer to table 1 again for explaining the treatment status of patient 3. As shown in table 1, patient 3 developed ischemic symptoms on postnatal day 1, and improvement in symptoms was observed after 10 days of treatment with the pharmaceutical composition of the present invention (after 10 days of treatment). In addition, the time for complete healing of ischemic symptoms in patient 3 was 24 days (after 24 days of treatment).

According to the results of the above experimental examples, it is shown that the pharmaceutical composition of the embodiment of the present invention can improve, even cure, the condition of limb (toe) ischemia in premature infants. In particular, although the above experimental examples are described with respect to the treatment of acroischemia in premature infants, the pharmaceutical composition and the use thereof of the present invention can also be used in neonates, infants or young children other than premature infants, the present invention is not limited thereto, and the treated part can also be used in other parts, such as, but not limited to, fingers, arms, calves, thighs, etc. In addition, although the carrier used in the pharmaceutical composition of the experimental example is illustrated by a gel, the pharmaceutical composition may include the carrier described in other parts of the present disclosure, and is not limited herein.

In conclusion, the pharmaceutical composition and the preparation application thereof can directly act on the ischemic tissue to promote the blood circulation of the local tissue so as to avoid numbness, pain, even purplish, blackened, ulcerated or necrotic tissues caused by ischemia of the local tissue, further achieve the efficacy of treating the ischemia and further avoid side effects caused by the action of the medicament on other tissues.

The foregoing is illustrative only and is not limiting. Any equivalent modifications or variations without departing from the spirit and scope of the present invention should be included in the claims of the present application.