CN111012766B - Pharmaceutical composition for preventing and treating pulmonary hypertension and preparation method and application thereof - Google Patents
Pharmaceutical composition for preventing and treating pulmonary hypertension and preparation method and application thereof Download PDFInfo
- Publication number
- CN111012766B CN111012766B CN201911236792.1A CN201911236792A CN111012766B CN 111012766 B CN111012766 B CN 111012766B CN 201911236792 A CN201911236792 A CN 201911236792A CN 111012766 B CN111012766 B CN 111012766B
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- pulmonary hypertension
- treating pulmonary
- preventing
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a pharmaceutical composition for preventing and treating pulmonary hypertension, a preparation method and application thereof. The pharmaceutical composition is prepared from an active component and pharmaceutically acceptable auxiliary materials, wherein the active component is prepared by mixing linalool, geraniol, myrtle alcohol and perillyl alcohol. The preparation method of the pharmaceutical composition comprises the step of preparing the active ingredients and pharmaceutically acceptable auxiliary materials into powder, pills, granules, capsules, tablets or liquid preparations and the like according to a conventional method in pharmaceutics. The pharmaceutical composition can be used for preparing a medicament for treating pulmonary hypertension. The active components of the pharmaceutical composition of the invention, namely linalool, geraniol, myrtle alcohol and perillyl alcohol, can significantly reduce pulmonary hypertension caused by hypoxia, and the pharmaceutical preparation of the invention has the advantages of simple preparation method, lower medication cost and improved convenience for treating pulmonary hypertension.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a pharmaceutical composition for preventing and treating pulmonary hypertension and a preparation method and application thereof.
Background
Pulmonary Arterial Hypertension (PAH) is a group of diseases or clinical syndromes characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance due to different etiologies, the pathogenesis of which includes vasoconstriction, vascular remodeling and thrombosis. The classification system proposed by the international primary pulmonary hypertension workshop classifies pulmonary hypertension into 5 types: 1) pulmonary hypertension associated with respiratory diseases and/or hypoxemia; 2) pulmonary venous hypertension; 3) chronic thrombotic and/or embolic disease; 4) pulmonary arteriolar hypertension; 5) directly affects pulmonary hypertension caused by pulmonary vascular tissue diseases. If PAH is left untreated, it can eventually lead to right heart failure, increased volume loading and death. At present, drugs for treating pulmonary hypertension are mainly vasodilators, such as alpha receptor blockers, calcium antagonists angiotensin converting enzyme inhibitors, phosphodiesterase inhibitors, Prostanoid (PG) drugs, nitro vasodilators, and the like. Although these drugs have the effects of improving the dyspnea of patients, 6-minute walking distance (6MWD), pulmonary hemodynamics, etc., they have various disadvantages in terms of therapeutic effects, preparation and administration costs, and convenience of treatment.
Linalool, geraniol, myrtanol and perilla alcohol are monoterpene substances and are widely present in plant volatile oil. Has antioxidant and antiinflammatory effects. There is no literature reporting a relevant effect of the above active ingredients on the treatment of pulmonary hypertension.
Disclosure of Invention
Based on the above, it is necessary to provide a therapeutic drug using linalool, geraniol, myrtle alcohol and perillyl alcohol as active ingredients, aiming at the problems of poor therapeutic effect, high drug preparation and administration cost and insufficient therapeutic convenience of the current pulmonary hypertension drugs.
A pharmaceutical composition for preventing and treating pulmonary hypertension is prepared from an active component and pharmaceutically acceptable auxiliary materials, wherein the active component is prepared by mixing linalool, geraniol, myrtle alcohol and perillyl alcohol.
The pharmaceutical composition for preventing and treating pulmonary hypertension comprises pharmaceutically acceptable carriers and conventional pharmaceutical excipients or auxiliary agents. In addition, colorants, preservatives, flavors, flavorings, sweeteners, or other materials may also be added to the pharmaceutical composition, if desired.
In one embodiment, the active component accounts for 0.1-99% of the total weight of the pharmaceutical composition.
In one embodiment, the mass ratio of linalool, geraniol, myrtle alcohol and perillyl alcohol in the active component is 3:3.5:2: 1.
The administration route of the pharmaceutical composition can be gastrointestinal tract or parenteral tract, such as oral, pulmonary, nasal, subcutaneous, sublingual, skin, muscle, rectum, etc., preferably oral administration.
The invention also relates to a preparation method of the pharmaceutical composition for preventing and treating pulmonary hypertension, which comprises the following steps: the active ingredients and pharmaceutically acceptable auxiliary materials are prepared into powder, pills, granules, capsules, tablets or liquid preparations and the like according to a conventional method in pharmaceutics.
The pharmaceutical composition may be administered in a solid, semi-solid or liquid form. The solid dosage form can be powder, pellet, dripping pill, granule, capsule (including hard capsule, soft capsule, and enteric capsule), tablet (including common tablet, enteric coated tablet, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, and orally disintegrating tablet), suppository, pellicle, patch, aerosol (powder), spray, etc.; semisolid dosage forms can be ointments, gels, pastes, etc.; the liquid dosage forms can be solutions, emulsions, suspensions, injections, eye drops, nasal drops, lotions, liniments, and the like.
The pharmaceutical composition can be prepared into common preparations, sustained release preparations, controlled release preparations, targeting preparations and various microparticle drug delivery systems.
The dose of the pharmaceutical composition of the present invention to be administered depends on many factors such as the nature and severity of the disease to be prevented or treated, the sex, age, body weight, character and individual response of the patient or animal, the administration route, the number of administrations, the therapeutic purpose, and thus the therapeutic dose of the present invention can be widely varied. The pharmaceutical composition of the present invention can be taken alone, or in combination with other therapeutic agents or symptomatic drugs and adjusted in dosage.
For the purpose of administration and enhancing the therapeutic effect, the drug of the present invention can be administered by any known administration method.
The invention also relates to application of the pharmaceutical composition for preventing and treating pulmonary hypertension in preparation of a drug for treating pulmonary hypertension.
Drawings
FIG. 1 is a schematic diagram showing the effect of the pharmaceutical composition for preventing and treating pulmonary hypertension on pulmonary arterial pressure of rats stimulated by hypoxia under different dosage conditions in comparison with a normal control group and a hypoxic control group;
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with figures are described in detail below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.
A pharmaceutical composition for preventing and treating pulmonary hypertension is prepared from an active component and pharmaceutically acceptable auxiliary materials, wherein the active component is prepared by mixing linalool, geraniol, myrtle alcohol and perillyl alcohol.
Preferably, the active component accounts for 0.1-99% of the total weight of the pharmaceutical composition.
Preferably, the mass ratio of linalool, geraniol, myrtle alcohol and perillyl alcohol in the active component is 3:3.5:2: 1.
A preparation method of a pharmaceutical composition for preventing and treating pulmonary hypertension comprises the following steps: the active ingredients and pharmaceutically acceptable auxiliary materials are prepared into powder, pills, granules, capsules, tablets or liquid preparations and the like according to a conventional method in pharmaceutics.
The application of the pharmaceutical composition for preventing and treating pulmonary hypertension in preparing a medicament for treating pulmonary hypertension is provided.
Compared with the prior art, the invention has the following advantages:
the active components of the pharmaceutical composition of the invention, namely linalool, geraniol, myrtle alcohol and perillyl alcohol, can significantly reduce pulmonary hypertension caused by hypoxia, and the pharmaceutical preparation of the invention has the advantages of simple preparation method, lower medication cost and improved convenience for treating pulmonary hypertension.
Examples
(1) Preparation of active ingredients:
weighing linalool, geraniol, myrtle alcohol and perilla alcohol according to the mass ratio of 3:3.5:2:1, and mixing for later use.
(2) Pharmacological activity test:
effect of lowering pulmonary artery pressure
Experimental animals: healthy male Sprague-Dawley (SD) rats, purchased from the animal experiment center of the university of Sigan traffic (the experimental animals use license number SCXK (shan) 2017-.
An experimental instrument: electron balance: SHANGPING (YP601N), Biopac Multi-lead physiological recorder, roller slicer (come card-2016, Germany); TSJ-II type fully automatic closed tissue dehydrator (Wien electronics Co., Ltd., Changzhou city); BMJ-III type embedding machine (Wei electronics, Inc. in the suburbs of Changzhou); PHY-III type bleaching and baking instrument for pathological tissues (Wei electronic instruments, Inc. in Changzhou city); a Digital trinocular image pickup microscope (BA400 Digital, mcondi industries group ltd), etc.; image analysis software Motic Images Advanced.
The pulmonary hypertension model replicates SD rats and is randomly grouped into 6 groups, which are respectively: normal Control group (Control): rats were anesthetized with 20% urethane abdominal cavity (0.5ml/0.1kg) on the same day and pulmonary artery pressure was measured, the thoracic cavity was opened after supine fixation, the heart and lung were quickly taken out, and the sample was taken and left; ② hypoxic control group (Hypoxia): the rat is placed in a low-pressure oxygen chamber for feeding (with the altitude of 5000 meters) for 30 days, and a rat HPH model is copied; ③ hypoxic administration drug group (VO): after hypoxia exposure, rats were administered daily gavage at doses of 390mg/kg, 293mg/kg, and 195mg/kg for 30 consecutive days.
Right ventricular systolic pressure was measured by catheterization: after 30 days, the rats of each group were anesthetized with 10g/L sodium pentobarbital (40mg/kg), fixed to an operating table, the right external jugular vein was isolated, the distal end was ligated, the proximal end was blocked with an arterial clamp, and the right jugular vein was cannulated with a polyethylene catheter (filled with 0.5% heparin solution in the catheter), and connected to a pressure transducer and a physiological recorder. After the catheter enters the blood vessel, the catheter is slowly pushed, the display of the recorder is observed at the same time, after the right ventricular artery pressure curve is displayed, the catheter is fixed, and the 30s pressure curve is recorded. Right-ventricular systole pressure (RVSP) was calculated by the recorder analysis software.
Measurement of right ventricular hypertrophy index: after the mPAP measurement is finished, the thoracic cavity of a rat is cut off immediately, the position of a catheter in the right ventricle is determined, the heart is taken out, left and right atrial tissues are cut off, right ventricular tissues are cut off along the edge of the ventricular septum, and the left and right ventricular tissues are weighed respectively. The right ventricular to left ventricular plus ventricular interval ratio (RV/LV + S), i.e., Right Ventricular Hypertrophy Index (RVHI), is calculated to determine the presence or absence of right ventricular hypertrophy.
Tissue sampling and fixing: lung small blood vessel remodeling observation and image processing, fixing the left lung tissue of a rat by neutral buffered formalin, embedding a section by paraffin, HE staining, and observing the pulmonary small blood vessel remodeling condition under a light mirror. The pulmonary artery with the diameter of about 100 mu m is taken, the morphological measurement analysis is carried out by an image analysis system, and the ratio (WT%) of the cross-sectional area of the blood vessel wall to the cross-sectional area of the blood vessel is taken as an index for measuring the low-oxygen pulmonary vascular remodeling.
Statistical analysis: the results of the experiment are expressed as mean ± standard deviation (mean ± SEM), and the data are analyzed using SPSS13.0 software. Differences between groups were analyzed using One-way ANOVA with statistical differences of P < 0.05.
The experimental results are as follows:
effect on average pulmonary artery pressure (mPAP) in HAPH rats: compared with a normal Control group (Control), the mPAP of the rat of the Hypoxia Control group (Hypoxia) is obviously increased (P is less than 0.05), which indicates that the model of the rat of the Hypoxia pulmonary hypertension is successfully constructed. As shown in FIG. 1, mPAP of rats subjected to hypoxia administration (VO) under each dose is obviously reduced (P < 0.05) compared with that of a model control group, which shows that the pulmonary hypertension caused by hypoxia can be obviously reduced by high, medium and low doses (390mg/kg, 293mg/kg and 195mg/kg) of the pharmaceutical composition.
The influence of the drug composition on pulmonary arteriolar vascular remodeling caused by hypoxia indicates that the drug composition can obviously inhibit the pulmonary arteriolar vascular remodeling at high, medium and low doses.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (5)
1. The pharmaceutical composition for preventing and treating pulmonary hypertension is characterized by being prepared from an active component and pharmaceutically acceptable auxiliary materials, wherein the active component is prepared by mixing linalool, geraniol, myrtle alcohol and perillyl alcohol.
2. The pharmaceutical composition for preventing and treating pulmonary hypertension according to claim 1, wherein the active component accounts for 0.1-99% of the total weight of the pharmaceutical composition.
3. The pharmaceutical composition for preventing and treating pulmonary hypertension according to claim 1 or 2, wherein the mass ratio of linalool, geraniol, myrtle alcohol and perillyl alcohol in the active components is 3:3.5:2: 1.
4. A method for preparing a pharmaceutical composition for preventing and treating pulmonary hypertension according to any one of claims 1 to 3, comprising the steps of: the active ingredients and pharmaceutically acceptable auxiliary materials are prepared into powder, pills, granules, capsules, tablets or liquid preparations according to a conventional method in pharmaceutics.
5. Use of the pharmaceutical composition for preventing and treating pulmonary hypertension according to any one of claims 1 to 3 in the preparation of a medicament for treating pulmonary hypertension.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911236792.1A CN111012766B (en) | 2019-12-05 | 2019-12-05 | Pharmaceutical composition for preventing and treating pulmonary hypertension and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911236792.1A CN111012766B (en) | 2019-12-05 | 2019-12-05 | Pharmaceutical composition for preventing and treating pulmonary hypertension and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111012766A CN111012766A (en) | 2020-04-17 |
| CN111012766B true CN111012766B (en) | 2020-11-03 |
Family
ID=70207355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911236792.1A Active CN111012766B (en) | 2019-12-05 | 2019-12-05 | Pharmaceutical composition for preventing and treating pulmonary hypertension and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111012766B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115192597A (en) * | 2022-08-08 | 2022-10-18 | 青海大学 | Pharmaceutical composition for preventing and treating pulmonary hypertension, preparation method and application thereof |
| CN115990202A (en) * | 2022-12-13 | 2023-04-21 | 青海大学 | Application of rhodiola rosea volatile oil in intervention of hypoxia-induced pulmonary hypertension and research method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1686455A (en) * | 2005-05-13 | 2005-10-26 | 北京正大绿洲医药科技有限公司 | Geranol drip pill and its preparation method |
| WO2006029142A2 (en) * | 2004-09-02 | 2006-03-16 | University Of Florida Research Foundation, Inc. | Methods and systems for treating asthma and other respiratory diseases |
| WO2007085899A3 (en) * | 2005-07-06 | 2008-07-10 | Foamix Ltd | Foamable arthropocidal composition for tropical application |
| CN106937962A (en) * | 2017-03-29 | 2017-07-11 | 青海大学 | A kind of three-flavor sandalwood dissipates preparation and the medical usage of total volatile oil |
-
2019
- 2019-12-05 CN CN201911236792.1A patent/CN111012766B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006029142A2 (en) * | 2004-09-02 | 2006-03-16 | University Of Florida Research Foundation, Inc. | Methods and systems for treating asthma and other respiratory diseases |
| CN1686455A (en) * | 2005-05-13 | 2005-10-26 | 北京正大绿洲医药科技有限公司 | Geranol drip pill and its preparation method |
| WO2007085899A3 (en) * | 2005-07-06 | 2008-07-10 | Foamix Ltd | Foamable arthropocidal composition for tropical application |
| CN106937962A (en) * | 2017-03-29 | 2017-07-11 | 青海大学 | A kind of three-flavor sandalwood dissipates preparation and the medical usage of total volatile oil |
Non-Patent Citations (1)
| Title |
|---|
| Conversion of volatile alcohols into their glucosides in Arabidopsis;Koichi Sugimoto et al;《Communicative & Integrative Biology》;20150129;第8卷(第1期);e992731第1-4页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111012766A (en) | 2020-04-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2021042248A (en) | Treatment of diastolic cardiac dysfunction with trpv2 receptor agonist | |
| JP6966196B2 (en) | Compositions and Methods Useful for the Treatment of Lower Urinary Tract Symptoms, Benign Prostate Hyperplasia, Erectile Dysfunction | |
| CN111012766B (en) | Pharmaceutical composition for preventing and treating pulmonary hypertension and preparation method and application thereof | |
| EP0257344A1 (en) | Medicaments containing dipyridamol or mopidamol and O-acetylsalicylic acid, or its physiologically compatible salts, process for their manufacture and their use in combating the formation of thrombus | |
| KR100445946B1 (en) | Treatment of Pulmonary Hypertensoin | |
| Young et al. | Baroreflex setting and sensitivity after acute and chronic nicardipine therapy | |
| EP1596868B1 (en) | Method for treating severe heart failure and medicament therefor | |
| WO2021037244A1 (en) | Pharmaceutical composition and application thereof | |
| CN103370101A (en) | Methods and compositions for treating HIV-associated diarrhea | |
| USRE36701E (en) | Coronary heart disease treated with oestradiol | |
| US20130209584A1 (en) | Pharmaceutical formulations of nitrite and uses thereof | |
| CN115192597A (en) | Pharmaceutical composition for preventing and treating pulmonary hypertension, preparation method and application thereof | |
| CN109369754B (en) | Nitrate ester compound and application thereof | |
| Liard | Effects of a specific antidiuretic agonist on cardiac output and its distribution in intact and anephric dogs | |
| US20150079183A1 (en) | Lercanidipine Hydrochloride and Losartan Potassium Compound Preparation and Preparation Method Thereof | |
| CN109893653A (en) | The new application of PDE9 inhibitor | |
| Miller et al. | Physiological changes of aging affecting salt and water balance | |
| US20200108047A1 (en) | Methods and compositions for treating congenital diarrhea disorder | |
| Murakami et al. | Beneficial Effect of Honeybee-collected Pollen Lump Extract on Benign Prostatic Hyperplasia (BPH)—A Double-blind, Placebo-controlled Clinical Trial— | |
| CN111514209A (en) | Application of traditional Chinese medicine composition in preparation of medicine for preventing and/or treating myocardial ischemia-reperfusion injury | |
| Ji et al. | Protective effect of casticin in myocardial ischemia/reperfusion injury in rats via attenuation of oxidative stress and inflammation | |
| EP2184284B1 (en) | Preventive, inhibitor or remedy for cerebral aneurysm comprising ibudilast as an active ingredient | |
| Stever et al. | Side effects of beta adrenergic antagonists and antianginal drugs | |
| CN110946894A (en) | Tibetan medicine for treating pulmonary hypertension and preparation method and application thereof | |
| US20200179308A1 (en) | Use of isohumulones and derivatives thereof to treat polycystic ovary syndrome |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |